Sesen Bio Annual Report 2018

Plain-text annual report

Table of Contents UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549 FORM 10-K (Mark One)xANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934For the fiscal year ended December 31, 2018ORoTRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF1934For the transition period from to Commission File No. 001-36296 Sesen Bio, Inc.(Exact name of registrant as specified in its charter) DELAWARE26-2025616(State or other jurisdiction ofincorporation or organization)(I.R.S. EmployerIdentification No.)245 First Street, Suite 1800Cambridge, MA02142(Address of principal executive offices)(Zip code)Registrant’s telephone number, including area code: (617) 444-8550 Securities registered pursuant to Section 12(b) of the Act:Title of each className of each exchange on which registeredCommon Stock, par value $0.001 per shareNasdaq Global MarketSecurities registered pursuant to Section 12(g) of the Act:None Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. o Yes x NoIndicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. o Yes x NoIndicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filingrequirements for the past 90 days. x Yes o NoIndicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 ofRegulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit suchfiles). x Yes o NoIndicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained, to the bestof registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form10-K. xIndicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or anemerging growth company. See the definitions of “large accelerated filer," “accelerated filer,” “smaller reporting company,” and “emerging growth company”in Rule 12b-2 of the Exchange Act.Large Accelerated fileroAccelerated filerxNon-accelerated filero Smaller reporting companyx Emerging growth companyxIf an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new orrevised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. xIndicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act.): o Yes x NoAs of June 29, 2018, the last business day of the registrant’s most recently completed second fiscal quarter, the aggregate market value of the Common Stockheld by non-affiliates of the registrant was approximately $132.0 million based on the closing price of the registrant’s common stock on June 29, 2018.Number of outstanding shares of Common Stock as February 27, 2019: 77,456,180 Table of ContentsSESEN BIO, INC.TABLE OF CONTENTS PagePART I Item 1.Business1Item 1A.Risk Factors55Item 1B.Unresolved Staff Comments101Item 2.Properties101Item 3.Legal Proceedings101Item 4.Mine Safety Disclosures101PART II Item 5.Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities102Item 6.Selected Financial Data103Item 7.Management’s Discussion and Analysis of Financial Condition and Results of Operations103Item 7A.Quantitative and Qualitative Disclosures About Market Risk119Item 8.Financial Statements and Supplementary Data119Item 9.Changes in and Disagreements with Accountants on Accounting and Financial Disclosure119Item 9A.Controls and Procedures119Item 9B.Other Information120PART III Item 10.Directors, Executive Officers and Corporate Governance121Item 11.Executive Compensation121Item 12.Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters121Item 13.Certain Relationships and Related Transactions, and Director Independence121Item 14.Principal Accountant Fees and Services121PART IV Item 15.Exhibits and Financial Statement Schedules122Item 16.Form 10-K Summary122iTable of ContentsFORWARD-LOOKING STATEMENTSThis Annual Report on Form 10-K contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statementsof historical facts, contained in this Annual Report on Form 10-K, including statements regarding our strategy, future operations, future product research ordevelopment, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. Thewords “anticipate,” “believe,” “goals,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,”“could,” “should,” “continue” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statementscontain these identifying words.The forward-looking statements in this Annual Report on Form 10-K include, among other things, statements about: •our expected future loss and accumulated deficit levels;•our projected financial position and estimated cash burn rate;•our estimates regarding expenses, future revenues, capital requirements and needs for, and ability to obtain, additional financing;•our ability to continue as a going concern;•our need to raise substantial additional capital to fund our operations;•the potential impairment of our goodwill and indefinite lived intangible assets;•the effect of recent changes in our senior management team on our business;•the success, cost and timing of our pre-clinical studies and clinical trials in the United States, Canada and in other foreign jurisdictions;•the potential that results of pre-clinical studies and clinical trials indicate our product candidates are unsafe or ineffective;•our dependence on third parties, including contract research organizations, or CROs, in the conduct of our pre-clinical studies and clinical trials;•the difficulties and expenses associated with obtaining and maintaining regulatory approval of our product candidates and companion diagnostics,if any, in the United States, Canada and in other foreign jurisdictions, and the labeling under any approval we may obtain;•our plans and ability to develop and commercialize our product candidates;•our ability to achieve certain future regulatory, development and commercialization milestones under our license agreement, which we refer to as theLicense Agreement, with F. Hoffmann-La Roche Ltd and Hoffmann La-Roche Inc., or collectively, Roche;•the timing and costs associated with our manufacturing process and technology transfer to FUJIFILM Diosynth Biotechnologies U.S.A., Inc., orFujifilm, and our reliance on Fujifilm to perform under such agreement;•market acceptance of our product candidates, the size and growth of the potential markets for our product candidates, and our ability to serve thosemarkets;•obtaining and maintaining intellectual property protection for our product candidates and our proprietary technology;•the successful development of our commercialization capabilities, including sales and marketing capabilities; and•the success of competing therapies and products that are or become available.Our product candidates are investigational biologics undergoing clinical development and have not been approved by or submitted for approval to the U.S.Food and Drug Administration, or FDA, Health Canada, or the European Commission. Our product candidates have not been, nor may they ever be, approvedby any regulatory agency or competent authorities nor marketed anywhere in the world.We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and our stockholders should not place unduereliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in theforward-looking statements we make. We have included important factors in the cautionary statements included in this Annual Report on Form 10-K,particularly in the “Risk Factors” section, that could cause actual results or events to differ materially from the forward-looking statements that we make. Ourforward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures or investments we may make.You should read this Annual Report on Form 10-K and the documents that we have filed as exhibits to this Annual Report on Form 10-K completely and withthe understanding that our actual future results may be materially different from what weTable of Contentsexpect. The forward-looking statements contained in this Annual Report on Form 10-K are made as of the date of this Annual Report on Form 10-K, and wedo not assume any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as requiredby applicable law.Table of ContentsPART IItem 1.Business.OverviewWe are a late-stage clinical company developing targeted fusion protein therapeutics, or TFPTs, composed of an anti-cancer antibody fragmenttethered to a protein toxin for the treatment of cancer. We genetically fuse the cancer-targeting antibody fragment and the cytotoxic protein payload into asingle molecule which is produced through our proprietary one-step manufacturing process. We target tumor cell surface antigens with limited expression onnormal cells. Binding of the target antigen by the TFPT allows for rapid internalization into the targeted cancer cell. We have designed our targeted proteinsto overcome the fundamental efficacy and safety challenges inherent in existing antibody-drug conjugates, or ADCs, where a payload is chemically attachedto a targeting antibody.Our most advanced product candidate, VB4-845, also known as Vicinium®, is a locally-administered targeted fusion protein composed of an anti-EPCAM, or epithelial cell adhesion molecule, antibody fragment tethered to a truncated form of Pseudomonas exotoxin A for the treatment of high-risk non-muscle invasive bladder cancer, or NMIBC.On January 3, 2019, we reported preliminary efficacy data for the primary endpoint of our ongoing single-arm, multi-center, open-label Phase 3clinical trial of Vicinium as a monotherapy in patients with high-risk, bacillus Calmette-Guérin, or BCG, unresponsive NMIBC, called the VISTA Trial. Thedata reported the preliminary complete response rates in evaluable Carcinoma in situ, or CIS, patients following three, six, nine and 12 months of treatment inthe clinical trial. The results were consistent with the results observed in the previously completed Phase 1 and Phase 2 clinical trials of Vicinium for thetreatment of high-risk NMIBC. The VISTA Trial enrolled a total of 133 patients across three cohorts based on histology and time to disease recurrence afteradequate BCG:•Cohort 1 (n=86): CIS patients with or without papillary disease whose cancer was determined to be refractory or recurred within six monthsof their last course of adequate BCG•Cohort 2 (n=7): CIS patients with or without papillary disease whose cancer was determined to be refractory or recurred after six months, butless than 12 months, after their last course of adequate BCG•Cohort 3 (n=40): patients with papillary disease without CIS whose cancer was determined to be refractory or recurred within six months oftheir last course of adequate BCGThe data reported built upon preliminary three-month data presented from a subset of patients in May 2018 and are for the primary endpoint of theVISTA Trial, which is the complete response rate, or CRR, and duration of response in patients in Cohort 1. We also reported data from Cohort 2, separatelyand pooled with Cohort 1, based on final FDA guidance on treatment of BCG-unresponsive CIS patients.The tables below highlight VISTA Trial results observed as of the December 3, 2018 data cut off:Preliminary Efficacy Results in Carcinoma in situ PatientsCohort 1 CRRs (n=86)Time pointEvaluable PatientsComplete Response Rate (95% Confidence Interval)3-monthsn=8637% (27%-48%)6-monthsn=8525% (16%-35%)9-monthsn=8418% (10%-28%)12-monthsn=8114% (7%-23%)Cohort 2 CRRs (n=7)1Table of ContentsTime pointEvaluable PatientsComplete Response Rate (95% Confidence Interval)3-monthsn=757% (18%-90%)6-monthsn=757% (18%-90%)9-monthsn=743% (10%-82%)12-monthsn=714% (0%-58%)Pooled Cohorts 1 and 2 CRRs (n=93)Time pointEvaluable PatientsComplete Response Rate (95% Confidence Interval)3-monthsn=9339% (29%-49%)6-monthsn=9227% (18%-37%)9-monthsn=9120% (12%-29%)12-monthsn=8814% (7%-23%)Preliminary Phase 3 CRR vs Phase 2 CRRTime pointPhase 3 Pooled CRR(95% Confidence Intervals)Phase 2 Pooled CRR(95% Confidence Interval)3-months39% (29%-49%)40% (26%-56%)6-months27% (18%-37%)27% (15%-42%)9-months20% (12%-29%)18% (8%-32%)12-months14% (7%-23%)16% (7%-30%)Cohort 3 Recurrence-Free Rate (n=40)*Time pointEvaluable PatientsRecurrence-Free Rate (95% Confidence Interval)3-monthsn=4068% (51%-81%)6-monthsn=4056% (40%-72%)9-monthsn=3942% (26%-59%)12-monthsn=3836% (21%-54%)*As of the December 3, 2018 data cut off, but not previously reported on January 3, 2019.Since the first preliminary data were reported in January, we have conducted additional analyses, including duration of response in patients withCarcinoma in situ with or without papillary disease, time to cystectomy across all patient types with Carcinoma in situ or papillary disease, and time todisease recurrence and recurrence-free rate in patients with papillary disease without Carcinoma in situ as of an assessment date of December 3, 2018. Theadditional preliminary data includes the following secondary endpoints:•Duration of Response: In addition to the complete response rate in Cohort 1, duration of response is a primary endpoint measure. Themedian duration of complete response for patients in Cohort 1 (n=86) is 227 days (95% CI, 127-516), using the Kaplan-Meier method.Additional adhoc analysis of pooled data for all patients with Carcinoma in situ (Cohorts 1 and 2, n=93) shows that among patients whoachieved a complete response at 3 months, 69% had a complete response of 6 months or longer.•Time to Cystectomy: Time to cystectomy is a key second endpoint in the VISTA Trial. Across all 133 patients treated with Vicinium, theprojected median cystectomy-free time is approximately 519 days (95% CI, 361-523), or 18 months. The median was estimated using acomputer-based, intensive, nonparametric approach commonly used in clinical trials to generate estimates and confidence intervals for datasets that are incomplete. Using the variability within a sample to estimate that sampling distribution empirically, 500 samples withreplacement were generated to estimate the median.2Table of Contents•Time to Disease Recurrence: Time to disease recurrence is a key secondary endpoint for patients with high-grade papillary-only (Ta and T1)NMIBC. The median time to disease recurrence for patients in Cohort 3 (n=40) is 270 days (95% CI, 169-452).•Recurrence-free Rate: Disease recurrence, a standard criterion to evaluate treatment response for patients with high-grade papillary-only (Taand T1) NMIBC, showed that for patients in Cohort 3 (n=40), Vicinium treatment resulted in favorable efficacy with 56% (95% CI, 40%-72%) of patients remaining recurrence-free at 6 months, and 36% (95% CI, 21%-54%) of patients remaining recurrence-free at 12 months.Preliminary Safety ResultsAs of the December 3, 2018 data cut off, in patients across all three cohorts (n=133), 78 percent of adverse events were Grade 1 or 2. The mostcommonly reported treatment-related adverse events were dysuria (13%), hematuria (12%) and urinary tract infection (11%) - all of which are consistent withthe profile of bladder cancer patients and the use of catheterization for treatment delivery. These adverse events were determined to be manageable andreversible, and only five patients discontinued treatment due to an adverse event. Serious adverse events, regardless of treatment attribution, were reported in14 percent of patients. There were four treatment-related SAEs reported in three patients including acute renal injury (Grade 3), pyrexia (Grade 2), cholestatichepatitis (Grade 4) and renal failure (Grade 5). Based on available preliminary follow-up data, no patient developed metastatic bladder cancer in the Phase 2clinical trial for Vicinium or the Phase 3 VISTA Trial (through the December 3, 2018 data cut off).The VISTA Trial completed recruitment in March 2018 with a total of 133 enrolled patients with NMIBC. We expect to report updated 12-monthdata from the VISTA Trial by mid-2019.On August 8, 2018, we received Fast Track designation from the FDA for Vicinium for the treatment of patients with high-risk NMIBC who havepreviously received two courses of BCG and whose disease is now BCG-unresponsive.On October 4, 2018, we entered into a Master Bioprocessing Services Agreement, or the Fujifilm MSA, with Fujifilm, pursuant to which Fujifilm will providecertain manufacturing services related to Vicinium. The Fujifilm MSA is designed to facilitate a transfer of certain of our manufacturing processes andtechnologies from us to Fujifilm to determine if Fujifilm can develop the bulk drug substance form of Vicinium for commercial purposes if we receiveregulatory approval to market Vicinium for the treatment of high-risk NMIBC.In June 2017, we entered into a Cooperative Research and Development Agreement, or CRADA, with the National Cancer Institute, or NCI, for thedevelopment of Vicinium in combination with AstraZeneca’s immune checkpoint inhibitor, durvalumab, for the treatment of high-risk NMIBC. Under theterms of the CRADA, the NCI will conduct a Phase 1 clinical trial in patients with high-risk NMIBC to evaluate the safety, efficacy and biological correlatesof Vicinium in combination with durvalumab. This Phase 1 clinical trial is open and is actively recruiting patients.Vicinium has also been evaluated for the treatment of squamous cell carcinoma of the head and neck, or SCCHN. Vicinium for the treatment ofSCCHN had previously been designated as ProxiniumTM to indicate its different fill volume and vial size as well as its different route for local administrationvia intratumoral injection.In addition to our locally-administered TFPTs, our pipeline also includes systemically-administered TFPTs in development that are built around ourproprietary de-immunized variant of the plant-derived cytotoxin bouganin, or deBouganin. Our lead systemically-administered product candidate, VB6-845d, is being developed for the treatment of multiple types of EpCAM-positive solid tumors. VB6-845d is a TFPT consisting of an EpCAM targeting Fabgenetically linked to deBouganin, a novel plant derived cytotoxic payload that we have optimized for minimal immunogenic potential and is administeredby intravenous infusion.We have deferred further development of Vicinium for the treatment of SCCHN and VB6-845d in order to focus our efforts and our resources on ourongoing development of Vicinium for the treatment of high-risk NMIBC. We are also exploring collaborations for Vicinium for the treatment of SCCHN, andVB6-845d.We maintain global development, marketing and commercialization rights for all of our TFPT-based product candidates. We intend to explorevarious commercialization strategies to market our approved products. If we obtain regulatory approval for Vicinium for the treatment of high-risk NMIBC,we may build a North American specialty urology sales force to market the product or seek commercialization partners. If we obtain regulatory approval forVicinium for the treatment of SCCHN or for our other product candidates, including VB6-845d, we may seek partners with oncology expertise in order tomaximize the commercial value of each asset or a portfolio of assets. We also own or exclusively license worldwide intellectual3Table of Contentsproperty rights for all of our TFPT-based product candidates, covering our key patents with protection ranging from 2018 to 2036. See ‘‘Business-IntellectualProperty’’ for additional details.On June 10, 2016, we entered into the License Agreement with Roche, pursuant to which we licensed our monoclonal antibody EBI-031 and allother IL-6 antagonist antibody technology owned by us. Under the License Agreement, Roche is required to continue developing EBI-031 and pursueongoing patent prosecution at its cost. At the time of the License Agreement, EBI-031, which was derived using our previous AMP-Rx platform, was in pre-clinical development as an intravitreal injection for diabetic macular edema and uveitis. We have received $30.0 million in payments from Roche pursuant tothe License Agreement, including a $7.5 million upfront payment and a $22.5 million milestone payment as a result of the IND application for EBI-031becoming effective. We are also entitled to receive up to an additional $240.0 million upon the achievement of other specified regulatory, development andcommercial milestones, as well as royalties based on net sales of potential future products containing EBI-031 or any other potential future productscontaining other IL-6 compounds.Our Targeted Fusion Protein Therapeutic Platform (TFPT)Our current product candidates are based on our proprietary TFPT platform and are focused on addressing areas of unmet medical need in cancer. Ournovel TFPTs have been designed to overcome the efficacy and safety challenges of existing ADCs and are being developed for both local and systemicadministration. Our TFPTs are single protein therapeutics composed of targeting domains genetically fused via peptide linkers to cytotoxic protein payloadsthat are produced through our proprietary recombinant one-step manufacturing process. Our TFPT platform uses protein binding antibody fragments, whichinclude fragment antigen binding domains, or Fabs, single chain variable domains, or scFvs, and non-covalent scFv dimers, or diabodies, derived from thedomains of antibodies that confer antigen recognition. We select antibody fragments for our product candidates depending upon the target therapeuticindication. We target tumor cell surface antigens that allow for rapid internalization into the targeted cancer cell and that also have limited expression innormal cells. For local administrations, we utilize an immunogenic cytotoxic protein payload designed to both target cancer cells and promote a heightenedlocal immune response against the tumor. For systemic administrations, we use a deBouganin, a plant-derived, protein payload of reduced immunogenicpotential that we believe can be repeatedly administered via infusion without the generation of an efficacy-limiting immune response against the payload.Locally-administered TFPTsWe utilize our TFPTs with immunogenic cytotoxic protein payloads for tumors that can be targeted locally rather than systemically. Localadministration allows for the TFPT to reach the tumor without being cleared by the immune system, which enables us to maximize the concentration ofTFPTs directly to tumors. Our locally-administered TFPT, Vicinium for the treatment of high-risk NMIBC, which is our lead product candidate, contains atargeting domain that is designed to bind to EpCAM, which is a protein over-expressed in many cancers. This targeting domain is genetically fused to atruncated form of exotoxin A, or ETA, which is an immunogenic cytotoxic protein payload that is produced by the bacterial species, Pseudomonas. Thisproduct candidate is designed to bind to EpCAM on the surface of cancer cells. The TFPT-EpCAM complex is subsequently internalized into the cell, and,once inside the cell, the TFPT is cleaved by a cellular enzyme to release the cytotoxic protein payload, thus enabling cancer-cell killing.We also believe that our TFPTs designed for local administration may not only directly kill cancer cells through a targeted delivery of a cytotoxicprotein payload, but also potentiate an anti-cancer therapeutic immune response in cancer cells near the site of administration. This immune response isbelieved to be triggered by both the immunogenic cell death of the cancer cells due to our payload's mechanism of action and the subsequent release oftumor antigens and the immunologically active setting created by the nature of the cytotoxic protein payloads. We believe that this immune response mayalso enhance the action of checkpoint inhibitors, which require a pre-existing immune response for maximum efficacy.Our most advanced locally-administered product candidate is Vicinium for the treatment of high-risk NMIBC and recurrent, locally advanced ormetastatic EpCAM-expressing SCCHN. This TFPTs is not, however, suitable for systemic administration over multiple doses because the body’s immunesystem would recognize and eliminate foreign proteins, such as ETA, prior to their reaching targeted cancer cells.Systemically-administered TFPTsWe also utilize our TFPTs with a de-immunized payload where systemic administration is required. Our systemically-administered TFPTs currentlyin development are built around deBouganin. Since the body’s immune system naturally recognizes and attempts to eliminate foreign proteins, we designedour systemically administered TFPTs with a deBouganin payload to avoid inducing an immunogenic response. DeBouganin is constructed by mutating theimmunogenic T-cell epitopes4Table of Contentsfrom bouganin so that they are not recognized as foreign by the immune system. However, we also believe that deBouganin may enhance the action ofcheckpoint inhibitors as a result of the promotion of a local tumor immune response following the death of cancer cells. Our systemically-administeredproduct candidate is VB6-845d for the treatment of multiple types of EpCAM-positive solid tumors.Our Differentiated Approach to Targeted TherapiesWe believe that our TFPT platform will address many challenges experienced with existing ADCs. The basic construct for our TFPTs and existingADCs is similar as each is comprised of a targeting domain that specifically binds to cancer cells and delivers a cytotoxic payload. However, existing ADCshave been associated with limitations that we believe are addressed by our TFPTs.Limitations of existing ADC approaches to treating tumorsWe believe existing ADCs have the following fundamental efficacy and safety challenges:•Deliver insufficient drug to tumors. Existing ADCs utilize full-length antibodies, which, due to their large size, have a reduced ability topenetrate tumors, thereby potentially reducing their efficacy.•Inability to kill a broad array of cancer cells within a tumor. Subsets of cancer cells within tumors may have mechanisms to resist and not beresponsive to the cytotoxic payloads, or small molecule chemotherapies, used in existing ADCs.•Off-target toxicities due to unstable chemical linkage between targeting antibody and cytotoxic payload. Existing ADCs utilize chemicallinkage strategies to join antibodies to small molecule cytotoxic payloads. While in the circulatory system, these chemical linkages can breakand release free cytotoxic payloads in the circulation. These free small molecule cytotoxic payloads are not targeted and cannot discriminatebetween dividing cancer cells and non-cancerous cells, thus resulting in increased off-target toxicities.•Limited combination therapy potential. The release of free cytotoxic payloads in the tumor region can result in toxicity to immune cells thatattack tumors. This effect on anti-tumor immune cells may limit the potential utility of existing ADCs in combination therapies, including thoseemploying immune checkpoint inhibitors.•Complex and challenging manufacturing process. The multi-step manufacturing process of existing ADCs creates a non-homogeneous productthat limits efficacy and drives greater costs than our manufacturing process.Advantages of our TFPT platformWe believe our TFPTs offer the following key advantages:•Deliver a greater amount of drug to tumors. Our TFPTs are designed using smaller targeting proteins that have an increased ability to exit thecirculatory system and have binding properties designed to enable deeper penetration into targeted tumors, and we believe this will increaseefficacy.•Ability to kill a broader array of cancer cells within a tumor. Our novel cytotoxic payloads consist of proteins rather than small moleculecytotoxic payloads. We believe the larger size of our cytotoxic protein payloads helps circumvent multi-drug resistance mechanisms that canmake certain cancer cells resistant to small molecule cytotoxic payloads. By contrast to existing ADCs, which employ cytotoxic payloads thatinhibit cellular replication and are effective at killing rapidly proliferating cancer cells, our cytotoxic protein payloads inhibit protein synthesisand are designed to kill not only rapidly proliferating, but also slowly growing cancer cells including tumor progenitor cells/cancer stem-likecells.•Increase safety due to a more stable linkage between targeting protein and cytotoxic payload. Our single protein molecules are designed toremain intact until they reach the inside of the cancer cell and to not release free cytotoxins into the circulatory system, thereby minimizing off-target toxicity.•Promote a therapeutic immune response. We believe that the potent TFPT toxin-mediated killing of cancer cells in this immunologicallyactive setting leads to the efficient presentation of cancer antigens to the immune system, thereby promoting an anti-tumor cellular immuneresponse. Our locally-administered TFPTs utilize an immunogenic cytotoxic payload that we believe promotes a heightened immune responsein the local tumor environment.•Potential combination with checkpoint inhibitors. We believe that the potential effect of checkpoint inhibitors, which are antibodies thatpromote the action of anti-tumor T-cells by blocking inhibitory ligand/receptor5Table of Contentsinteractions that include PD-1 and PD-L1, may be enhanced when used in combination with other agents. We believe that, by mediatingspecific killing of tumor cells and promoting anti-tumor immune responses, our TFPTs, while potentially effective on their own, maycomplement checkpoint inhibitors. In particular, we believe that our use of our cytotoxin payload ETA, which promotes an immune response inthe local tumor environment, may facilitate the presentation of tumor cell surface antigens following the death of cancer cells, therebyproviding a tumor immune response to enhance the action of checkpoint inhibitor therapies.•Utilize a simpler and more efficient manufacturing process. Our proprietary recombinant one-step manufacturing process creates ahomogeneous product that we believe will improve efficacy and result in lower manufacturing costs.Our StrategyWe are committed to designing, engineering, developing and commercializing TFPTs to identify and address oncology indications that suffer from ahigh unmet medical need. The key elements of our strategy are as follows:•Rapidly advance Vicinium for the treatment of high-risk NMIBC through clinical development and obtain regulatory approval. Based uponour September 2014 end of Phase 2 meeting with the FDA, in the third quarter of 2015, we, through our subsidiary Viventia, commenced anopen-label, non-randomized Phase 3 clinical trial, the VISTA Trial, of Vicinium in patients with high-risk NMIBC in the United States andCanada. In November 2016, the FDA issued draft guidance regarding appropriate clinical trial design for new drugs and biologics for BCG-unresponsive NMIBC, including the use of single-arm studies. The FDA finalized this guidance in February 2018 and retained many of therecommendations from the 2016 draft guidance regarding clinical trial design, including the use of single-arm studies. We believe that thePhase 3 clinical trial VISTA Trial design is consistent with these aspects of the FDA’s guidance. We completed enrollment in the VISTA Trial inMarch 2018 and reported preliminary topline three-month efficacy and safety data for the VISTA Trial in May 2018. On January 3, 2019, wereleased preliminary three-month, 6-month, 9-month and 12-month topline efficacy and safety data and further expect to report updated 12-month topline efficacy and safety data in mid-2019. In August 2018, we received Fast Track designation from the FDA for Vicinium for thetreatment of high-risk NMIBC. If this Phase 3 clinical trial is successful, we intend to pursue regulatory approval initially in the United Statesand Canada. Assuming that we receive positive data in our Phase 3 clinical trial, we intend to initiate discussions with the European MedicinesAgency, or EMA, regarding a regulatory pathway for European Union, or E.U., approval.•Explore opportunities in combination therapies. We plan to continue discussions with potential partners that utilize technologies whosemechanism of action could be complementary to our TFPT platform. These technologies include, but are not limited to, checkpoint inhibitors,immune modulators and other immuno-oncology agents. In June 2017, we entered into a CRADA with the NCI for the development of Viciniumin combination with AstraZeneca’s immune checkpoint inhibitor, durvalumab, for the treatment of NMIBC. Under the terms of the CRADA, theNCI will conduct a Phase 1 clinical trial in patients with high-risk NMIBC to evaluate the safety, efficacy and biological correlates of Viciniumin combination with durvalumab. This Phase 1 trial is open and actively recruiting patients.•Expand on the value of selected product candidates through strategic partnerships. We may decide to selectively partner with pharmaceuticaland biopharmaceutical companies when we believe that a partner could bring additional resources and expertise to maximize the value of oneor more of our product candidates.•Maximize the commercial value of our product candidates. We maintain global development, marketing and commercialization rights for allof our TFPT-based product candidates. If we obtain regulatory approval for Vicinium for the treatment of high-risk NMIBC, we may build aNorth American specialty urology sales force to market the product in the United States and Canada or seek commercialization partners. Outsidethe United States and Canada, we will seek commercialization partners with urology expertise. If we obtain regulatory approval for our otherproduct candidates, or other indications for Vicinium, we may seek partners with oncology expertise in order to maximize the commercial valueof each asset or a portfolio of assets.We have deferred further development of Vicinium for the treatment of SCCHN and VB6-845d in order to focus our efforts and our resources on ourongoing development of Vicinium for the treatment of high-risk NMIBC. We are also exploring collaborations for Vicinium for the treatment of SCCHN, andVB6-845d.Our License Agreement with Roche6Table of ContentsOn June 10, 2016, we entered into the License Agreement with Roche. Under the License Agreement, we granted Roche an exclusive, worldwidelicense to develop and commercialize, at its cost, our monoclonal antibody EBI-031 and all other IL-6 antagonist antibody technology owned by us.Pursuant to the terms of the License Agreement, Roche is required to continue developing EBI-031 and any other product made from the other transferred IL-6 antagonist antibody technology, and pursue ongoing patent prosecution, at its cost.Roche paid an upfront license fee of $7.5 million and a $22.5 million milestone payment as a result of the IND application for EBI-031 becomingeffective. Roche has also agreed to pay up to an additional $240.0 million upon the achievement of specified regulatory, development and commercialmilestones. In addition, we are entitled to receive royalty payments in accordance with a tiered royalty rate scale, with rates ranging from 7.5% to 15% for netsales of potential future products containing EBI-031 and up to 50% of these rates for net sales of potential future products containing other IL-6 compounds,with each of the royalties subject to reduction under certain circumstances and to the buy-out options of Roche.Our Product PipelineAt this time we are focused exclusively on the clinical development of Vicinium for the treatment of high-risk NMIBC and have deferred furtherdevelopment of our other product candidates. The following table sets forth our current development stage programs:7Table of ContentsVicinium for the Treatment of High-Risk NMIBCOverviewVicinium is being developed for the treatment of high-risk NMIBC in patients who have previously received two courses of BCG and whose diseaseis now BCG-unresponsive. Vicinium is administered by intravesical administration directly into the bladder. Vicinium utilizes an immunogenic cytotoxicprotein payload that is a truncated form of ETA produced by the bacterial species, Pseudomonas. Vicinium also includes an anti-EpCAM ScFv targetingdomain that is required to deliver the ETA into EpCAM-expressing cancer cells. The toxicity to non-cancerous bladder cells is minimized due to their nothaving EpCAM over-expressed on their surface.Based upon our September 2014 end of Phase 2 meeting with the FDA, we, through our subsidiary Viventia, commenced the VISTA Trial in patientswith high-risk NMIBC who have received two courses of BCG, and whose disease is now BCG-unresponsive, and for whom the current standard of care is thesurgical removal of their bladder, or a radical cystectomy, in the third quarter of 2015 in the United States and Canada. Based on safety and efficacy dataobserved with the longer 12-week induction in our Phase 2 clinical trial, the FDA agreed to our plan to employ more frequent dosing in our Phase 3 clinicaltrial, in which the primary end points are CR and duration of response, or DoR, in patients with carcinoma in situ, or CIS, whose disease is BCG-unresponsive.In November 2016, the FDA issued draft guidance regarding appropriate clinical trial design for new drugs and biologics for BCG-unresponsive NMIBC,including the use of single-arm studies. The FDA finalized this guidance in February 2018 and retained many of the recommendations from the 2016 draftguidance regarding clinical trial design, including the use of single-arm studies. We completed enrollment in this clinical trial in May 2018, and reportedpreliminary topline three-month data in May 2018 and three-month, 6-month, 9-month and 12-month preliminary topline data on January 3, 2019. Weexpect to report updated 12-month topline twelve-month data in mid-2019. In August 2018, we received Fast Track designation from the FDA for Viciniumfor the treatment of high-risk NMIBC. If this Phase 3 clinical trial is successful, we intend to pursue regulatory approval initially in the United States andCanada. Assuming that we receive positive data in our Phase 3 clinical trial, we intend to initiate discussions with the European Medicines Agency, or EMA,regarding a regulatory pathway for European Union, or E.U., approval.Overall, we believe that our efficacy and safety data support the continued clinical development of Vicinium to fulfill a significant unmet medicalneed in patients with high-risk NMIBC. Because Vicinium contains ETA, an immunogenic cytotoxic payload that elicits an anti-ETA immune response, webelieve the local administration of Vicinium may amplify the local host immune response within the tumor environment killing bladder cancer cells throughan Immunogenic Cell Death, or ICD, mechanism. In addition, we believe that this ICD response, which potentiates host immune responses againstneoantigens present on the cancer cells, can lead to a heightened host immune response against their own tumor and potentially complement checkpointinhibitor therapies.We own or exclusively license worldwide rights to our Vicinium intellectual property portfolio that provides unextended patent term until June2025, and, if our pending patent applications for Vicinium are granted patent protection until at least 2036. See ‘‘Business-Intellectual Property’’ foradditional details.Disease overviewMost cancers that form in the bladder are transitional cell carcinomas that derive from the transitional cell lining of the bladder. Transitional cellcarcinoma of the bladder can be characterized as either high-grade or low-grade. Low-grade bladder cancer often recurs in the lining of the bladder aftertreatment, but rarely invades the muscular wall of the bladder or spreads to other parts of the body and is unlikely to be fatal. High-grade bladder cancercommonly recurs in the bladder, has a strong tendency to invade the muscular wall of the bladder, and spread to other parts of the body and is much morelikely to result in death. Bladder cancer is also divided into muscle-invasive and NMIBC, based on invasion of the muscularis propria, which is the thickmuscle deep in the bladder wall. Muscle invasive disease is more likely to spread to other parts of the body.There are three forms of high-grade NMIBC, Ta, a papillary tumor in the innermost layer of the bladder lining, T1, a papillary tumor that has startedto grow into the connective tissue beneath the bladder lining, and CIS, flat lesions of the transitional cell lining of the bladder. Papillary tumors are generallylow-grade with low risk of progression, although about two to nine percent are high-grade, with a moderately high risk of progression to muscle-invasivebladder cancer. CIS tumors are always high-grade, with a worse prognosis than papillary tumors, as such CIS tumors are more aggressive, with a higherprobability of progression to muscle-invasive disease. Furthermore, the incidence of CIS in conjunction with Ta or T1 tumors results in a higher risk ofrecurrence and progression. About 75% to 85% of bladder cancers are non-muscle invasive. Of these, Ta tumors account for about 57% to 70%, CIS accountsfor about 5% to 13% and T1 tumors account for about 20% to 30%.8Table of ContentsBladder cancer is the tenth most common cancer diagnosed worldwide and the second most common malignancy of the genitourinary system. Therewere an estimated 430,000 new cases of bladder cancer diagnosed in 2012 and 165,000 deaths worldwide. The global prevalence of bladder cancer isestimated at 2.7 million individuals. The American Cancer Society estimated that approximately 81,000 new cases of bladder cancer would be diagnosed in2018 and there would be approximately 17,240 deaths due to bladder cancer in the United States during 2018. Based on a 2010 estimate prepared usingMedicare data from the Surveillance, Epidemiology, and End Results program, among cancers in the United States, bladder cancer has the highest per-patienttreatment costs, with an estimated overall cost of approximately $4.0 billion annually. In the United States, bladder cancer has the highest overall cost amongthe elderly. Based on our assessment of the market, the treatment paradigm has remained the same since those figures were generated and we believe the costof care has increased.NMIBC makes up 75% to 85% of all bladder cancers. The high recurrence rate and ongoing invasive monitoring requirement of bladder cancers arethe key contributors to the economic and human toll of this disease. Bladder cancer occurs predominantly in older patients (about nine of the 10 people withbladder cancer are over the age of 55 years). The median age at diagnosis is approximately 72 years. Overall, the five year survival rate for bladder cancer inthe United States is 77%. While the five year survival rates are 98% for stage zero and 88% for stage one NMIBC, once the cancer becomes invasive, the ratesdrop dramatically with five year survival rates of 63%, 46% and 15% for stage two, three and four muscle invasive bladder cancers, respectively. We aretargeting patients with BCG-unresponsive high-risk NMIBC. Our initial target market includes the approximately 25,000 patients diagnosed annually, aswell as the patients who have previously failed BCG and have refused cystectomy. We would expect that, if Vicinium for the treatment of high-risk NMIBC isapproved by the FDA, patients would receive treatment until the earlier of 2 years and disease recurrence.Current approaches to treatmentWithin high-risk NMIBC, the initial treatment of Ta or T1 is transurethral resection of the bladder tumor, or TURBT, followed by BCG treatment. ForCIS, whether or not TURBT is an option, BCG is the standard of care. BCG is a live attenuated strain of Mycobacterium bovis, with a diminished virulence inhumans. Since BCG works by utilizing an immune/inflammatory mechanism, BCG is generally initiated only two to four weeks after TURBT, allowing theurothelium to heal and lowering the risk of systemic infection. When high-grade bladder tumors have been completely resected, BCG is used as adjuvanttherapy to prevent recurrence. In patients with residual disease after resection, BCG helps to eradicate residual disease and delay progression. The BCGregimen consists of an induction phase followed by a maintenance phase. The induction phase involves six consecutive once-weekly instillations of the druginto the bladder. The maintenance phase involves three consecutive once-weekly instillations repeated every three to six months for at least one year. Theresponse rate to a single induction phase of BCG is 60% to 70% with an additional 30% to 50% of the non-responders becoming responders following asecond induction phase. However, BCG’s failure rate for all responders is estimated to be as high as 50% within the first 12 months of treatment and 90%within five years.For patients who received BCG, and whose disease is now BCG-unresponsive, radical cystectomy is recommended due to the risk of progression tomuscle invasive disease, which greatly reduces a patient’s prognosis. Radical cystectomy is a complex surgery associated with a significant morbidity rate of28% to 45% and a mortality rate of 8% within six months of surgery. The surgery also entails a number of short-term risks including bleeding and/or clots,infections, bowel obstruction, bowel perforation, peritonitis and injury to the urethra. More than 25% of radical cystectomy patients require readmission forsurgery-related complications within 90 days following surgery, and 34% require emergency room visits. The impact of radical cystectomy is life-altering,with major lifestyle changes, including incontinence and sexual dysfunction, and daily issues related to management of the external bag for urine collection.In 2009, Valstar was re-launched in the United States for the treatment of BCG-refractory CIS bladder cancer in patients for whom radical cystectomyis not an option. Valstar is administered intravesically directly into the bladder once a week for six weeks. Due to drug resistance and toxicities, Valstar hashad limited utility. Other than Valstar, there are no other approved therapies for CIS bladder cancer. However, there are various other intravesical productcandidates in development for the treatment of NMIBC, including product candidates developed by Merck (Keytruda/pembroluzumab) AADi, LLC (ABI-009), Altor BioScience Corp. (ALT-801), Cold Genesys, Inc. (CG0070) and FKD Therapies Oy (Instiladrin). In addition, systemically-administeredcheckpoint inhibitors are being evaluated for the treatment of NMIBC.Clinical trials and pre-clinical studiesPre-clinical studies. Our in vitro studies of Vicinium in bladder cancer cell lines demonstrated activity following an exposure time equivalent toclinical dosing. The anti-tumor activity of Vicinium was also evaluated against human tumor xenografts (SCCHN, colorectal and small cell lung carcinomacell lines) using an athymic mouse model. Mice bearing9Table of ContentsEpCAM-positive human tumor xenografts implanted subcutaneously were administered 0.25-0.5 mg/kg of Vicinium by intravenous injection, and tumor sizemonitored over the course of the pre-clinical study (33 to 51 days post-initiation of treatment) and compared to that of an untreated tumor-bearing group.Vicinium demonstrated significant tumor growth suppression. Vicinium is designed to be a local therapy and is administered by intravesical instillationdirectly to the bladder. Vicinium repeatedly administered subcutaneously in both rats and cynomolgus monkeys did not result in any product candidate-related systemic toxicity. Toxicities associated with subcutaneous administration were limited to localized irritation with skin lesions resolving by the end ofthe pre-clinical study. Vicinium was found to be immunogenic in all species tested with anti-drug antibodies observed after seven days of dosing.Phase 1 clinical trial. We initiated an open-label, dose-escalating Phase 1 clinical trial of Vicinium for the treatment of high-risk NMIBC inSeptember 2004 at 22 sites in Canada. We enrolled 64 patients with high-grade Ta or T1 tumors with or without CIS (17 of which had CIS) and who hadpreviously received at least one treatment of BCG. The Phase 1 clinical trial was designed to assess safety and determine the maximum tolerated dose, and therecommended Phase 2 dose. The secondary objective was to explore the anti-tumor activity of Vicinium.Eight dose levels were initially evaluated, ranging from 0.1 to 10.56 mg dose given once weekly for six consecutive weeks. Each dose wasadministered by instillation and held for two hours prior to voiding. Safety data from each dose cohort was evaluated after three weeks of treatment beforeproceeding to the next dose cohort. A maximum tolerated dose was not reached; therefore, additional escalations through 13.73 mg, 17.85 mg, 23.20 mg and30.16 mg were undertaken. No dose-limiting toxicities, or DLTs, were reported and no maximum tolerated dose was reached in these additional dose-escalations. Vicinium was generally well-tolerated at each of these escalated doses.A CR was defined in this Phase 1 clinical trial as non-positive urinary cytology and either normal cystoscopy or abnormal cystoscopy with negativebiopsy. Of the 64 patients enrolled, only 61 were considered to be evaluable for efficacy as two patients were excluded from the analysis due to an absence ofBCG treatment prior to this Phase 1 clinical trial, and there was one unrelated death for whom no final tumor assessment was obtained. Evidence of clinicalefficacy, as defined by a CR, was achieved by 24 of the 61 randomized patients (39%). Only three of the 17 patients (18%) treated in the 0.1-<1mg/dose rangewere CRs. In contrast, seven of the 14 patients (50%) treated in 1.0-<10mg/dose range and 14 of the 30 patients (46.7%) treated in the ≥10mg/dose rangeexperienced CRs at the three month assessment. Of the patients with CIS, five of the 17 patients (29%) achieved a CR, while non-recurrence was observed inseven of the 16 patients with T1 (43.8%) and 12 of the 28 patients with Ta (42.8%). This Phase 1 clinical trial was completed in April 2006.Phase 2 clinical trial. Based on our Phase 1 clinical trial conducted in Canada, we submitted the IND for Vicinium for the treatment of high-riskNMIBC to the FDA in August 2005, and we initiated an open-label Phase 2 clinical trial of Vicinium in March 2007 at 20 sites, in Canada and the UnitedStates. We enrolled 46 patients with CIS (with or without Ta or T1) who had previously received at least one treatment of BCG. Of the 46 patients enrolled,27 patients (58.7%) had received at least two treatments of BCG. The Phase 2 clinical trial was designed to determine the tolerability and explore thepotential for clinical benefit from Vicinium. Clinical benefit was defined in this Phase 2 clinical trial as a CR or no evidence of disease at the three monthevaluation. A CR was defined in this Phase 2 clinical trial as no histological evidence of disease and negative urine cytology. Any cases with no histologicalevidence of disease on initial biopsy but atypical or suspicious urine cytology were also considered CRs only if they remained negative after being evaluatedwith repeat biopsy, directed and random. Vicinium showed evidence of clinical efficacy. A patient was considered to have a durable CR if that patientobtained a CR and remained disease-free for a period of at least 12 months from initiation of treatment.The dosing regimen for our Phase 2 clinical trial included an induction phase followed by a maintenance phase, consisting of three weeklytreatments and then nine weeks of no treatment repeated every three months for at least one year and ending with nine weeks of no treatment. There were twotreatment groups in this Phase 2 clinical trial. Treatment Arm A consisted of 23 patients, of which 22 were ultimately evaluable as one patient violatedeligibility requirements early in this Phase 2 clinical trial. Twenty-two patients in the induction phase received six consecutive once-weekly instillations of30 mg of Vicinium. At the three-month assessment, patients with residual disease but no disease progression-where disease progression is defined as beingmuscle invasive-were eligible for either a second induction phase or a maintenance phase, which consisted of three consecutive once-weekly instillationsrepeated every three months for at least one year. Of the 13 patients unable to achieve a CR at the three-month assessment, nine patients elected additionaltreatment. From these nine, two became CRs after receiving maintenance dosing. Treatment Arm B was added to evaluate a longer induction cycle. InTreatment Arm B, 23 patients in the induction phase received 12 consecutive once-weekly instillations of 30 mg Vicinium. At the three-month assessment,the CR rate for both treatment arms was 40%. At the 12-month assessment, the CR rate in Treatment Arm A was 13%, but 17% in Treatment Arm B. Of thosepatients who did not achieve a CR at the three-month assessment, 73% had either a reduction in tumor size or did not experience further tumor growth.10Table of ContentsThe following charts demonstrate the responses in this Phase 2 clinical trial in Treatment Arm A and Treatment Arm B. The data below shows thepercentage change in surface area of cancer within the bladder, based on bladder mapping data utilizing cystoscopy in 40 patients.11Table of ContentsThis Phase 2 clinical trial was completed in September 2009.Near the completion of this Phase 2 clinical trial in 2009, Valstar was re-launched in the United States for the treatment of BCG-refractory CISbladder cancer in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. However, because physicians werenot widely prescribing Valstar to their patients and it was not an approved therapy in Europe, this disrupted our originally designed clinical path of a head-to-head pivotal Phase 3 clinical trial of Vicinium against Valstar. Due to the uncertainty of the standard of care in this space, our efforts were put on hold untila clear clinical path was established. In May 2013, the FDA co-sponsored a public workshop where it evaluated potential trial designs for the development oftherapies for NMIBC and specifically provided regulatory guidance supporting the idea that a single-arm clinical trial could provide sufficient evidence ofbenefit if the results were robust. The panel suggested it is acceptable to include high-risk papillary patients without CIS in a clinical trial with CIS patientsbecause the clinical management and outcome if left untreated is considered to be the same. In September 2014, we conducted an end of Phase 2 meetingwith the FDA and, consistent with our interactions with the FDA during this meeting, refocused our resources to commence an open-label, non-randomizedPhase 3 clinical trial of Vicinium in patients with high-risk NMIBC.Safety data. We believe that our safety data from 110 patients in our Phase 1 and Phase 2 clinical trials support further development of Vicinium forthe treatment of high-risk NMIBC. There were no Grade 4 or Grade 5 serious adverse events that were considered by the clinical investigators to be related toVicinium. There was one Grade 5 serious adverse event, or death, which was determined by the clinical investigator to be unrelated to Vicinium. The mostcommon reported treatment-related adverse events were an abnormally frequent passage of small amounts of urine, blood in the urine and painful urination,the majority of which were considered to be mild or moderate in severity. No patients discontinued treatment due to a Vicinium-related adverse event duringthe Phase 1 and Phase 2 clinical trials.Vicinium Phase 3 clinical trial development planPhase 3 Clinical Trial. Based upon our September 2014 end of Phase 2 meeting with the FDA, we, through our subsidiary Viventia, commenced theVISTA Trial in the third quarter of 2015 in the United States and Canada. Based on safety and efficacy data observed with the longer 12-week induction inour Phase 2 clinical trial, the FDA agreed to our plan to employ more frequent dosing in our Phase 3 clinical trial, in which the primary end points are CR andDoR in patients with CIS whose disease is BCG-unresponsive. In November 2016, the FDA issued draft guidance regarding appropriate clinical trial designfor new drugs and biologics for BCG-unresponsive NMIBC, including the use of single-arm studies. The FDA finalized this guidance in February 2018 andretained many of the recommendations from the 2016 draft guidance regarding clinical trial design, including the use of single-arm studies. We believe thatour Phase 3 clinical trial VISTA Trial design is consistent with these aspects of the FDA’s guidance.As part of this trial, in July 2015, we submitted a Clinical Trial Application, or CTA, to Health Canada to include Canadian sites. In September 2015,we received a No Objection Letter from Health Canada, permitting us to proceed with our Phase 3 clinical trial in Canada.Our Phase 3 clinical trial protocol is as follows:Dose 30 mg of Vicinium (in 50 mL of saline)Estimated total enrollment Approximately 134 patients, including 77 CIS patients whose disease is refractory to or relapsed within 6months of the last dose of adequate BCG treatmentPrimary endpoint •Complete response rate in patients with CIS (with or without papillary disease) whose disease is refractory orrelapsed in six months or less following adequate BCG treatment, which is defined as at least two courses offull dose BCG; and •DoR will be estimated (Kaplan-Meier Estimate) for those patients with CIS whose disease is refractory to orrelapsed within 6 months of the last dose of adequate BCG treatment (with or without papillary disease) whoexperience a complete response.Patients with CIS will be considered to have a complete response if at the time of any disease status evaluation (per protocol every 13 weeks or anyunscheduled evaluation) there is no evidence of high-grade disease (CIS, high-grade Ta or high-grade T1 disease) or disease progression (e.g., to muscleinvasive disease). Low-grade disease is not considered a treatment failure in these patients and they may remain on study treatment following TURBT.12Table of ContentsSecondary endpoints •Complete response rate and DoR in patients with CIS whose disease is refractory to or relapsed within 6months of the last dose of adequate BCG treatment (with or without papillary disease) whose disease isrefractory or relapsed from six months to 11 months following adequate BCG treatment; •Complete response rate and DoR in all patients with CIS (with or without papillary disease) followingadequate BCG treatment; •Event-free survival, or EFS, in all patients; •Complete response rate in patients at three, six, nine, 12, 15, 18, 21, and 24 months in patients with CISwhose disease is refractory to or relapsed within 6 months of the last dose of adequate BCG treatment; •Time to cystectomy in all patients; •Time to disease recurrence in all patients; •Progression-free survival, or PFS, in all patients; •Overall survival, or OS, in all patients; and •Safety and tolerability of Vicinium therapy in all patients. Exploratory endpoint To evaluate biomarkers that may be associated with response or disease progression or treatment failure, whichmay include, for example, EpCAM status, tumor subtype morphology, furin levels in tumor cell endosomes,presence of a glycosaminoglycan coat, and presence of receptors that could impede a host anti-tumor immuneresponse such as PD-L1.On January 3, 2019, we reported preliminary efficacy data for the primary endpoint of the VISTA Trial. The data reported the preliminary completeresponse rates in evaluable CIS patients following three, six, nine and 12 months of treatment in the clinical trial. The results were consistent with the resultsobserved in the previously completed Phase 1 and Phase 2 clinical trials of Vicinium for the treatment of high-risk NMIBC. The VISTA Trial enrolled a totalof 133 patients across three cohorts based on histology and time to disease recurrence after adequate BCG:•Cohort 1 (n=86): CIS patients with or without papillary disease whose cancer was determined to be refractory or recurred within six months of theirlast course of adequate BCG;•Cohort 2 (n=7): CIS patients with or without papillary disease whose cancer was determined to be refractory or recurred after six months, but lessthan 12 months, after their last course of adequate BCG; and•Cohort 3 (n=40): patients with papillary disease without CIS whose cancer was determined to be refractory or recurred within six months of their lastcourse of adequate BCGThe data reported built upon preliminary three-month data presented from a subset of patients in May 2018 and are for the primary endpoint of theVISTA Trial, which is the complete response rate, or CRR, and duration of response in patients in Cohort 1. The company also reported data from Cohort 2,separately and pooled with Cohort 1, based on final FDA guidance on treatment of BCG-unresponsive CIS patients.The tables below highlight VISTA Trial results observed as of the December 3, 2018 data cut off:Preliminary Efficacy Results in Carcinoma in situ PatientsCohort 1 CRRs (n=86)Time pointEvaluable PatientsComplete Response Rate (95% Confidence Interval)3-monthsn=8637% (27%-48%)6-monthsn=8525% (16%-35%)9-monthsn=8418% (10%-28%)12-monthsn=8114% (7%-23%)13Table of ContentsCohort 2 CRRs (n=7)Time pointEvaluable PatientsComplete Response Rate (95% Confidence Interval)3-monthsn=757% (18%-90%)6-monthsn=757% (18%-90%)9-monthsn=743% (10%-82%)12-monthsn=714% (0%-58%)Pooled Cohorts 1 and 2 CRRs (n=93)Time pointEvaluable PatientsComplete Response Rate (95% Confidence Interval)3-monthsn=9339% (29%-49%)6-monthsn=9227% (18%-37%)9-monthsn=9120% (12%-29%)12-monthsn=8814% (7%-23%)Preliminary Phase 3 CRR vs Phase 2 CRRTime pointPhase 3 Pooled CRR(95% Confidence Intervals)Phase 2 Pooled CRR(95% Confidence Interval)3-months39% (29%-49%)40% (26%-56%)6-months27% (18%-37%)27% (15%-42%)9-months20% (12%-29%)18% (8%-32%)12-months14% (7%-23%)16% (7%-30%)Cohort 3 Recurrence-Free Rate (n=40)*Time pointEvaluable PatientsRecurrence-Free Rate (95% Confidence Interval)3-monthsn=4068% (51%-81%)6-monthsn=4056% (40%-72%)9-monthsn=3942% (26%-59%)12-monthsn=3836% (21%-54%)*As of the December 3, 2018 data cut off, but not previously reported on January 3, 2019.Since the first preliminary data were reported in January, we have conducted additional analyses, including duration of response in patients withCarcinoma in situ with or without papillary disease, time to cystectomy across all patient types with Carcinoma in situ or papillary disease, and time todisease recurrence and recurrence-free rate in patients with papillary disease without Carcinoma in situ as of an assessment date of December 3, 2018. Theadditional preliminary data includes the following secondary endpoints:14Table of Contents•Duration of Response: In addition to the complete response rate in Cohort 1, duration of response is a primary endpoint measure. Themedian duration of complete response for patients in Cohort 1 (n=86) is 227 days (95% CI, 127-516), using the Kaplan-Meier method.Additional adhoc analysis of pooled data for all patients with Carcinoma in situ (Cohorts 1 and 2, n=93) shows that among patients whoachieved a complete response at 3 months, 69% had a complete response of 6 months or longer.•Time to Cystectomy: Time to cystectomy is a key second endpoint in the VISTA Trial. Across all 133 patients treated with Vicinium, theprojected median cystectomy-free time is approximately 519 days (95% CI, 361-523), or 18 months. The median was estimated using acomputer-based, intensive, nonparametric approach commonly used in clinical trials to generate estimates and confidence intervals for datasets that are incomplete. Using the variability within a sample to estimate that sampling distribution empirically, 500 samples withreplacement were generated to estimate the median.•Time to Disease Recurrence: Time to disease recurrence is a key secondary endpoint for patients with high-grade papillary-only (Ta and T1)NMIBC. The median time to disease recurrence for patients in Cohort 3 (n=40) is 270 days (95% CI, 169-452).•Recurrence-free Rate: Disease recurrence, a standard criterion to evaluate treatment response for patients with high-grade papillary-only (Taand T1) NMIBC, showed that for patients in Cohort 3 (n=40), Vicinium treatment resulted in favorable efficacy with 56% (95% CI, 40%-72%) of patients remaining recurrence-free at 6 months, and 36% (95% CI, 21%-54%) of patients remaining recurrence-free at 12 months.Preliminary Safety Results. Data indicates Vicinium for the treatment of high-risk NMIBC continues to be well-tolerated by patients treated in the VISTATrial. As of the December 3, 2018 data cut off, in patients across all three cohorts (n=133), 78% of adverse events were Grade 1 or 2. The most commonlyreported treatment-related adverse events, or AEs, were dysuria (13%), hematuria (12%) and urinary tract infection (11%) - all of which are consistent with theprofile of bladder cancer patients and the use of catheterization for treatment delivery. These AEs were determined to be manageable and reversible, and onlyfive patients discontinued treatment due to an adverse event. Serious adverse events, or SAEs, regardless of treatment attribution, were reported in 14% ofpatients. There were four treatment-related SAEs reported in three patients including acute renal injury (Grade 3), pyrexia (Grade 2), cholestatic hepatitis(Grade 4) and renal failure (Grade 5). Based on available preliminary follow-up data, no patient developed metastatic bladder cancer in the Phase 2 clinicaltrial for Vicinium or the Phase 3 VISTA Trial (through the December 3, 2018 data cut off).Vicinium for the Treatment of SCCHNOverviewVicinium (formerly referred to as Proxinium in publications focused on this clinical setting), is also being developed as a treatment for patients withrecurrent or metastatic EpCAM-expressing SCCHN who have received at least one prior platinum-based chemotherapy regimen with recurrent, locallyadvanced or metastatic EpCAM-expressing SCCHN. In SCCNH, Vicinium is administered via injection directly into the targeted tumor, or intratumoralinjection. Vicinium for the treatment of SCCHN has received Orphan Drug Designation from the FDA and the EMA and Fast Track designation from the FDA.In our two Phase 1 clinical trials, patients treated with Vicinium had demonstrated antitumor activity in 53% of evaluable patients with EpCAM-expressing tumors as assessed by the investigators’ clinical measurements, the investigators' overall assessment including qualitative changes, andassessment of available radiologic data. In addition, three out of the four patients with complete responses of injected tumors had regression or completeresolution of adjacent non injected lesions. In a Phase 2 clinical trial, we observed tumor shrinkage in 10 of the 14 evaluable patients (71.4%). Combinedresults from two Phase 1 clinical trials encompassing 44 patients have shown complete resolution or reduction in size of injected tumors in 16 of the 30evaluable EpCAM-positive patients (53.3%). An additional 27% of evaluable patients had stable disease and, therefore, the results indicate an overall tumorcontrol rate of approximately 80%. Vicinium was generally well-tolerated during the clinical trials. Dose-limiting toxicity in the Phase 1 clinical trials wastransaminase elevation in liver enzymes.In our clinical trials involving Vicinium for the treatment of SCCHN, we have also observed some stabilization, partial reduction and completeresolution of non-injected tumors. We believe that TFPT mediated killing of cancer cells occurs via a mechanism known as ICD, which is known to enhancethe presentation of neoantigens to the immune system. We believe that this, combined with the immunogenic nature of our cytotoxic protein payload createsa heightened immune response, wherein naive cytotoxic T cells are stimulated by antigen presenting cells, such as dendritic cells, presenting tumor cellsurface antigens following the death of cancer cells. We believe that this anti-tumor response may complement checkpoint inhibitor therapies.15Table of ContentsWe intend to initiate a Phase 1/2a clinical trial that will explore the potential of Vicinium in combination with a checkpoint inhibitor for thetreatment of SCCHN and are actively seeking partners for a combination program. We anticipate that the Phase 1/2a clinical trial will explore the potentialfor Vicinium, due to its potential immunogenic effect, to enhance checkpoint inhibitors in combination therapy for the treatment of SCCHN. We will bemeasuring both the objective response rates and immune response biomarkers in a Phase 1/2a clinical trial. Should a trial yield encouraging results and weare able to secure additional funding, we will move into later stage trials.During a Type C meeting with FDA in 2007, the FDA noted that approval of a companion diagnostic for EpCAM expression would need to coincidewith Vicinium approval for the treatment of SCCHN. During the clinical evaluation of Vicinium for the treatment of SCCHN, we developed animmunohistochemical test to determine whether clinical trial patients are EpCAM-positive. Internal examination from head and neck cancer patients showedthat our EpCAM antibody bound to 84% of all patient tumor samples we assessed. We intend to seek the FDA’s input as to whether thisimmunohistochemical test satisfies the FDA’s request for a companion diagnostic for EpCAM expression in this indication and whether we will need tosubmit this test for pre-market approval as a companion diagnostic in conjunction with Vicinium.Overall, we believe that our efficacy and safety data support the continued clinical development of Vicinium for the treatment of SCCHN to fulfill asignificant unmet medical need in patients with recurrent, locally advanced or metastatic EpCAM-expressing SCCHN.We believe the local administration of Vicinium mediates ICD of cancer cells leading to the release of tumor-specific neoantigens andattracting/activating cells of the host immune system. Further, Vicinium contains ETA, an immunogenic cytotoxic payload. The local activation of an anti-ETA response may further heighten the local immune response. We also believe that the effect of checkpoint inhibitors may be enhanced if they are used incombination with Vicinium due to its potential immunogenic effect.We have deferred further development of Vicinium for the treatment of SCCHN in order to focus our efforts and our resources on our ongoingdevelopment of Vicinium for the treatment of high-risk NMIBC. We are also exploring collaborations for the development of Vicinium for the treatment ofSCCHN.We own or exclusively license worldwide rights to our Vicinium for the treatment of SCCHN intellectual property portfolio that provide unextendedpatent term until June 2025 and, if our pending composition of matter patent applications for Vicinium are granted, until at least 2036. See ‘‘Business-Intellectual Property’’ for additional details.16Table of ContentsDisease overviewHead and neck cancers, which include cancers of the oral cavity, pharynx and larynx, are collectively the sixth most common cancers in the world.Head and neck cancer develops from the mucosal linings of the upper aerodigestive tract, comprising of the nasal cavity and paranasal sinuses, thenasopharynx, the hypopharynx, larynx, and trachea, and the oral cavity and oropharynx. Squamous cell carcinoma is the most frequent malignant tumor ofthe head and neck region. Invasive head and neck cancers arise in most cases from preneoplastic lesions grouped under the term dysplasia. Dysplastic lesionspresent with an increased likelihood of progressing to squamous cell carcinoma. The altered epithelium displays architectural and cytological changes thatrange from mild to severe.There are approximately 650,000 new cases annually and nearly 350,000 deaths due to head and neck cancer. In head and neck cancer,approximately 40% to 60% of deaths result from local or regional disease. The American Cancer Society estimates that there will be approximately 64,690new cases of head and neck cancers in the United States in 2018, of which 51,540 cases would be attributed to cancers of the oral cavity and pharynx and13,150 cases would be attributed to cancer of the larynx, and 13,740 deaths. Most of head and neck cancers are biologically similar with more than 90%being squamous cell carcinomas that commonly originate in the epithelium. They are strongly associated, more so than other cancers, with certainenvironmental and lifestyle risk factors, and worldwide incidence exceeds 650,000 cases annually.New treatment modalities have been undermined by the approximately 10% to 25% of cured patients who subsequently develop second primarytumors due to field cancerization. These second primary tumors are one of the leading factors in the 40% to 50% five year survival rate. Based on ourimmunohistochemical test used during our clinical trials of Vicinium for the treatment of SCCHN, we believe that approximately 84% of late-stage SCCHNare EpCAM-positive. We are initially developing Vicinium to potentially address late-stage SCCHN. We would expect that, if Vicinium for the treatment ofSCCHN is approved by the FDA, patients would receive treatment until disease progression.Current approaches to treatmentExisting treatment options for SCCHN include immunotherapy (checkpoint inhibitors), surgery, drug therapies, radiation therapy or a combinationof therapies. There is no standard treatment option for patients who progress after receiving these treatments. Approximately 60% of patients with head andneck cancer have locally recurrent disease and distant metastases occur in 20% to 30% of patients.Currently, Erbitux, an anti-epidermal growth factor receptor antibody, is the only FDA approved tumor-targeted therapy for the treatment of late-stage SCCHN. Erbitux has been approved as a first-line therapy for late-stage SCCHN in combination with platinum-based therapy plus fluorouracil. Erbituxhas also attained approval as a monotherapy or in combination with radiation therapy for second-line treatment of late-stage SCCHN in patients that havefailed platinum-based therapy.The five year survival rate for patients with locally recurrent disease is reported to be 40% to 50% and loco-regional recurrence is the predominantcause of failure and up to 70% of such patients have advanced disease. In addition, more than 50% of all patients who die from head and neck cancers haveloco-regional disease as the only site of failure. If head and neck cancers are not controlled locally, they can infringe on the esophagus and airway,compromising nutrition and respiratory functions and often resulting in significant anatomic disfigurement. As such, the management of locally recurrentdisease requires a multidisciplinary approach involving an array of specialists with an expertise in head and neck cancers.Most recently checkpoint inhibitors have entered into use in the treatment of SCCHN. Two checkpoint inhibitors that target PD-1, pembrolizumaband nivolumab, have now received approval for the treatment of SCCHN. Nivolumab was granted FDA approval for the treatment of patients with SCCHNwho have progressed on or after platinum-based chemotherapy. Nivolumab-treated patients had a 30% reduction in the risk of death; a median OS of 7.5months for nivolumab and 5.1 months for investigator's choice, or IC. There were no statistically significant differences between the two arms for progression-free survival or objective response rate, or ORR (13.3% versus 5.8% for nivolumab and IC, respectively). Pembrolizumab was granted accelerated approval bythe FDA for the treatment of patients with SCCHN who have progressed on or after platinum-based chemotherapy. The major efficacy outcome measures wereORR according to Response Evaluation Criteria in Solid Tumors, or RECIST version 1.1, as assessed by blinded independent central review, and duration ofresponse. The ORR was 16% (95% CI: 11, 22) with a complete response rate of 5%.17Table of ContentsClinical trials and pre-clinical studiesPre-clinical studies. Pre-clinical data from in vitro and in vivo studies of Vicinium for the treatment of SCCHN have demonstrated the potential to besafe in humans and to have clinical activity. In vitro pharmacology studies have demonstrated that Vicinium exhibits potent cytotoxicity against numerousEpCAM-positive cell lines, including SCCHN, bladder tumor and prostate tumor cell lines. Vicinium has also demonstrated anti-tumor activity in severalhuman tumor xenograft animal models expressing EpCAM, including those derived from human squamous cell carcinomas and in a lung cancer subjectderived xenograft, or PDX, model. In the PDX model, mice engrafted with human bone marrow cells were each implanted with two subcutaneous EpCAM-positive human PDX tumors. Tumor-bearing animals were treated with Vicinium alone in one tumor, an anti-PD-1 checkpoint inhibitor alone givensystemically, or a combination of the two. Intratumoral injection of Vicinium into the tumor xenograft located on one side of the animal was able to block thegrowth of the tumor while also having a quantifiable anti-tumor effect on the uninjected tumor on the opposite flank. In contrast, the checkpoint inhibitoralone had little effect on tumor growth but appeared to amplify Vicinium's activity on the uninjected tumor.18Table of Contents Vicinium treatment alone was also observed to increase the numbers of CD8+ T cells, an important cytotoxic immune cell population, in the blood.We believe that this indicates that the checkpoint inhibitor alone was ineffective in initiating the anti-tumor effects of immune cells without the prioractivation of cancer specific immune cells by a cytotoxic regimen, such as Vicinium.Further, synergistic and additive effects were observed in these in vitro pharmacology studies with Vicinium for the treatment of SCCHN incombination with various anti-cancer agents, as well as with radiation therapy. Toxicological studies in Sprague-Dawley rats showed no clear evidence ofsystemic toxicity whether given via intradermal or subcutaneous injection. The only dose-related reactions were at the injection site with most lesionsresolving by the end of the observation period. Plasma concentrations of animals in a seven-day toxicology study conducted in Sprague-Dawley rats were 50ng/mL at four hours after squamous cell injection and approximately 1,000 ng/mL at 10 minutes following intravenous injection on day one. These bloodlevels were approximately 5- and 100-fold higher, respectively, than the mean Cmax measured in patients administered 700 mg weekly for four weeks(10,936 pg/mL) through the intratumoral route. In in vivo pharmacology studies in human tumor xenograft mouse models, we observed evidence of tumorgrowth suppression.In summary, in vitro and in vivo pre-clinical data have shown that the anti-cancer agent Vicinium preferentially binds to tumor cells and has anacceptable safety profile. The local and systemic toxicological profile for Vicinium in Sprague-Dawley rats has been defined with toxicological effects atdoses 1,000-fold greater than the IC50 for activity on tumor cells.First Phase 1 clinical trial. We initiated an open-label, dose-escalating Phase 1 clinical trial of Vicinium for the treatment of SCCHN in December2003 at three sites in Russia. We enrolled 24 patients with late-stage SCCHN who had previously undergone prior radiation therapy, with a majority havingcompleted at least one chemotherapy cycle. In addition, based on our immunohistochemical test used during this Phase 1 clinical trial of Vicinium, 17 of the24 patients (70.8%) enrolled in this Phase 1 clinical trial had tumors that tested positive for EpCAM. The Phase 1 clinical trial was designed to19Table of Contentsdetermine the maximum tolerated dose and the recommended Phase 2 dose. Secondary objectives included evaluation of safety, tolerability, PK profile andefficacy endpoints.In addition, information on PK properties and immunogenicity, as well as a preliminary assessment of tumor response, was obtained.Patients received two cycles of Vicinium administered once per day for five consecutive days, with doses ranging from 20 µg to 280 µg, followed by23 days off. Two DLTs occurred at the 280 µg dose level, establishing 200 µg as the maximum tolerated dose. The DLTs observed in the two patients wereelevated liver enzyme tests, which were not associated with any signs of liver damage or toxicity, were asymptomatic and were transient as they resolved tobaseline values.Objective anti-tumor responses were measured by caliper, CT scans and digital photography from baseline to final assessment. Anti-tumor responsesand stable disease were observed in six of the 14 (42.9%) and four of the 14 (28.6%) evaluable patients with EpCAM-positive tumors, respectively, for anoverall response rate of 71.4% (10 of the 14 evaluable patients). All six of the evaluable patients with EpCAM-negative tumors had progression of their targettumors. In addition, the 10 patients with EpCAM-positive tumors and who had responses or stable disease had a survival time of 278 days compared with asurvival time of 124 days for the six patients with EpCAM-negative tumors. The 14 evaluable EpCAM-positive patients had a survival time of 207 days. ThisPhase 1 clinical trial was completed in October 2004.Second Phase 1 clinical trial. We initiated a second open-label, dose-escalating Phase 1 clinical trial of Vicinium for the treatment of SCCHN inJune 2004 at four sites in Brazil. We enrolled 20 patients with late-stage SCCHN. All of the patients enrolled in this Phase 1 clinical trial had undergone priorradiation therapy, with a majority having completed at least one chemotherapy cycle. Eighteen of the 20 patients (90%) tested positive for EpCAM, of whichtwo patients were non-clinically evaluable. Preliminary efficacy data indicated 14 of the 16 evaluable EpCAM-positive patients (87.5%) had either a‘‘complete resolution,’’ ‘‘response,’’ or ‘‘stable’’ disease of injected tumors following Vicinium treatment, with 25% of patients achieving a ‘‘completeresponse’’ of the injected tumor. The second Phase 1 clinical trial was designed to determine the maximum tolerated dose and the recommended Phase 2dose. Secondary objectives included evaluation of safety, tolerability, PK profile and efficacy endpoints.Patients received Vicinium once weekly for four weeks with initial doses ranging from 100 µg to 930 µg, followed up by four weeks with onceweekly doses ranging from 100 µg to 930 µg. The maximum tolerated dose was established at 700 µg, based on the occurrence of DLTs in two of the fivepatients at the 930 µg dose level cohort. The DLTs observed in the two patients were elevated liver enzyme tests. In both cases, the elevated liver enzymetests were not associated with any signs of liver damage or toxicity, were asymptomatic, and resolved to baseline values.Therapeutic exploratory endpoints were analyzed to evaluate the tumor response and anti-tumor activity of Vicinium. RECIST criteria were not usedin this Phase 1 clinical trial and instead the clinical investigator used the following definitions for tumor responses: ‘‘complete response’’ was the completeclinical resolution of a tumor (injected or non injected), ‘‘response’’ was defined as clinically and radiologically documented reduction in the size of thetarget tumor indicative of anti-tumor activity from baseline to final, ‘‘stable’’ was defined as no change in the disease state captured through clinical orradiological assessments from baseline to final and ‘‘progression’’ was defined as an increase in the size of the target tumor from baseline to the finalassessment.The following table demonstrates the response rate of patients with EpCAM-positive tumors in this Phase 1 clinical trial:Number ofComplete StableResponse ofevaluable patientsresponseResponseresponseprogression16.................................4 of the 166 of the 164 of the 162 of the 16 (25.0%)(37.5%)(25.0%)(12.5%)An example of a ‘‘complete’’ response obtained in a Vicinium injected tumor in the second Phase 1 clinical trial can be seen in FIGURE 1,FIGURE 2, FIGURE 3 and FIGURE 4 below:20Table of ContentsA non injected tumor response was observed in four of the 20 patients (20%) in the second Phase 1 clinical trial where patients were administeredVicinium weekly and one of the 15 patients (6.7%) in the Phase 2 clinical trial, which is discussed below, where patients were administered Vicinium weekly.In such cases, tumor responses were seen in loco-regional tumors that themselves had not been injected with Vicinium, but were adjacent to, and in one casebi-lateral to the injected tumor. An example of a non-target tumor response is shown in FIGURE 3 and FIGURE 4 above. We believe that this non-targettumor response may be a consequence of surrounding cancer cells dying in response to Vicinium through diffusion (or the local spread of Vicinium) andcross priming of the immune system or the selective release of cancer antigens into the local immune tumor environment. This Phase 1 clinical trial wascompleted in March 2005.Phase 2 clinical trial. We submitted the IND for Vicinium to the FDA in August 2005. We initiated an open-label Phase 2 clinical trial of Viciniumin March 2006 at 9 sites in Canada and 21 sites in the United States. We enrolled 15 patients with refractory locally recurrent disease, which means that thepatient must have progressed on or after receiving, or was unable to tolerate, at least one anti-cancer treatment regimen or had to have previously documentedrefusal of treatment for locally recurrent disease. The Phase 2 clinical trial was designed to determine the safety, tolerability and recommended dose ofintratumorally injected Vicinium. Secondary objectives were to evaluate principal target tumor and target tumor response rates, determine the time toprogression of the principal target tumor, overall survival time and progression-free survival, and also to confirm the PK profile and assess immunogenicity ofintratumorally injected Vicinium.The dosing regimen for our Phase 2 clinical trial included intratumoral injections once per week at 500µg or 700µg. Although the small sample sizedoes not allow for statistical evaluation of treatment effects, it was expected that the Phase 2 clinical trial would provide some additional evidence of thetherapeutic effect of Vicinium for control of local or regional late-stage SCCHN, as well as a survival benefit for those patients. To be eligible formeasurement of a radiographically confirmed response, a patient had to have a radiographic assessment at baseline/day one and at least two additionalradiographic21Table of Contentsassessments, not less than four weeks apart, after day one. According to this definition, eight patients were eligible for a principal tumor radiological responseevaluation. In order to assess best tumor response, at least two CT scans, one at baseline and one post-baseline, were required. Best tumor response wasdefined in this Phase 2 clinical trial as the greatest degree of decrease in tumor size observed throughout the clinical trial. Bidimensional tumor measurementswere used to determine tumor size. Bidimensional measurements of a tumor were based on its longest diameter and the greatest perpendicular measurementfrom this diameter from CT scans.RECIST criteria were not used in this Phase 2 clinical trial and instead the clinical investigator used the following definitions for tumor responses. A‘‘complete response’’ was defined in this Phase 2 clinical trial as the clinically and radiologically documented complete disappearance of the principal targettumor or other target tumors, based on bidimensional measurement as determined by two radiological observations not less than four weeks apart. A ‘‘partialresponse’’ was defined in this Phase 2 clinical trial as a 50% or more decrease of the bidimensional measurements in the principal target tumor that had beenmeasured as compared to baseline. ‘‘Progressive disease’’ was defined in this Phase 2 clinical trial as either: at least a 25% increase of the bidimensionalmeasurements for tumors greater than four cm2 or at least a 50% increase of the bidimensional measurements for tumors less than four cm2 in the principaltarget tumor as compared to the nadir, which was defined in this Phase 2 clinical trial as the smallest radiologically determined tumor size achieved duringthe clinical trial. ‘‘Stable disease’’ was defined in this Phase 2 clinical trial as disease that meets neither the ‘‘partial response’’ nor the ‘‘progressive disease’’criteria during or following active treatment and based on the sum of its bidimensional measurements, includes a less than 25% increase in tumor size fortumors greater than four cm2, or a less than 50% increase in tumor size for tumors less than four cm2. Tumor measurements that were radiographicallyconfirmed showed that four of the eight evaluable patients (50%) demonstrated ‘‘stable disease’’ for their principal tumor.When radiographic best responses were evaluated at any two treatment time points, including baseline, 13 of the 14 evaluable patients (92.9%)showed ‘‘stable disease’’ or partial response, with 10 of the 14 evaluable patients (71.4%) showing a decrease in tumor size ranging from 4% to 85%.Measurements of the principal target tumors taken at baseline and at final visit showed that three of the eight evaluable patients (37.5%) had decreases inprincipal tumor size ranging from 4% to 35%. Of five patients with multiple tumors who achieved primary tumor responses, four of those patients alsoachieved responses in subsequently injected non-primary tumors. These results suggest that Vicinium may be effective in the treatment of EpCAM-positivelate-stage SCCHN.This Phase 2 clinical trial for the treatment of SCCHN was completed in August 2007.The intention of the Phase 2 period of the clinical trial was evaluation of available data once the first 30 patients reached the four-week treatmenttime point. Of the first 30 patients enrolled, 15 were randomized to each study arm. The Phase 2 lead in period was specifically designed for the assessment ofsafety, with an independent review of the safety data by the data safety monitoring board, or DSMB. Following the review by the DSMB, they recommendedthe continuation of enrollment and monitoring as mandated by the protocol since the available data indicated that intratumoral administration of Viciniumwas generally well-tolerated by the patients. The Phase 3 period began immediately after the conclusion of the Phase 2 period, with no pause in enrollment.Phase 3 clinical trial. We initiated a randomized Phase 3 clinical trial of Vicinium for the treatment of SCCHN in January 2006 at 75 sites globally.Total enrollment was planned for 292 patients with late-stage SCCHN and the protocol included two periods: a Phase 2 lead-in period comprised of 30patients and a Phase 3 period comprised of 262 patients. Each subject’s locally recurrent disease had to be refractory, which means that the patient must haveprogressed on or after receiving, or was unable to tolerate, at least one anti-cancer treatment regimen or had to have previously documented refusal oftreatment for locally recurrent disease.This Phase 3 clinical trial was conducted to compare the overall survival time associated with intratumorally injected Vicinium and safety andefficacy data of Vicinium in combination with BSC versus BSC alone, in patients with locally recurrent disease who had received at least one anti-cancertreatment regimen for such locally recurrent disease. Secondary objectives were to compare the loco-regional response rate and duration of loco-regionalresponse, the local progression-free survival, symptomatic benefit and safety profile for patients from the Vicinium in combination with BSC arm and theBSC alone arm.During the treatment phase of this Phase 3 clinical trial, all patients were assessed weekly and treated according to institutional standards of BSC,which included treatment measures such as the use of pain medication, hydration, antiemetics and nutritional support, but did not include the use ofradiotherapy (except as needed for the palliation of distant metastases) or any agent that may have had an impact on tumor response. Patients who wererandomized to the BSC alone arm were either seen in the clinic or had weekly assessments conducted by phone; provided that at least one in-person visit wasconducted22Table of Contentsevery four weeks. Patients who were randomized to Vicinium in combination with the BSC arm were also to receive BSC, as well as a once weeklyintratumoral injection of Vicinium at 700 µg per dose. Patients in both arms of this Phase 3 clinical trial continued in the treatment phase until eithercomplete resolution of all target tumors or radiographic tumor progression occurred. All patients were then to remain in the follow-up phase until one of thefollowing occurred: (i) 12 months from the date that the last patient required for efficacy analyses had been randomized, died, withdrew or we terminated thetrial or (ii) termination of the trial for safety reasons due to DLTs.There were 62 patients for which post-treatment tumor measurements were available, 36 patients in the Vicinium in combination with the BSC armand 26 patients in the BSC alone arm. Responses in FIGURE 5 below represent the best percentage change in radiographically determined bidimensionalmeasurement from baseline at any time point for the injected tumor. Of the Vicinium in combination with BSC arm, 19 of the 36 patients (52.8%) showedtumor reduction with a median reduction in bidimensional tumor measurement of 48.3%. In contrast, only 10 of the 26 patients (38.5%) of the BSC alone armshowed a median reduction in tumor size of 21.9%. With respect to the patients for whom the best bidimensional percent change showed an increase in tumorsize, the Vicinium in combination with BSC arm had 12 of the 36 patients (33.3%) showing a median increase of 31.7%. The increase in tumor size was morepronounced in the BSC alone arm with 11 of the 26 patients (42.3%) showing a median increase of 60.8%.Targeted tumor responses in FIGURE 5 below were categorized as ‘‘complete,’’ ‘‘partial,’’ ‘‘stable,’’ or ‘‘progressive’’ disease. A ‘‘complete’’response was defined as radiographically confirmed complete disappearance of disease, ‘‘partial’’ response as a 50% or more decrease of the sum of theproduct of the bidimensional measurements as compared to baseline, and ‘‘progressive’’ disease as at least a 25% increase in the sum of the products of thebidimensional measurements compared to the radiographic nadir, when the sum at baseline was greater than four cm2 or at least a 50% increase of the sum ofthe product(s) of the bidimensional measurements compared to the radiographic nadir, when the sum at baseline was less than or equal to four cm2. ‘‘Stable’’disease was defined as the response when neither the complete response, partial response nor the progressive disease criteria were met.This Phase 3 clinical trial for the treatment of SCCHN was terminated in April 2008 because of challenges relating to patient enrollment andretention for reasons specific to emerging markets, but not due to safety or efficacy concerns. Clinical trial patient enrollment and retention in emergingmarkets presents unique challenges compared to North America. With fewer23Table of Contentsestablished options for communicating with existing and new patients, emerging market study centers have difficulty acquiring new patients as well asmaintaining consistent contact with existing patients, making follow up very difficult. We do not believe these issues will pose the same challenges in aNorth American SCCHN clinical trial. In the United States, study centers have established multiple options to enroll and remain in communication withpatients.At the time this SCCHN Phase 3 clinical trial was terminated, 166 patients had been randomized in the trial. Of these, 82 patients were randomized tothe Vicinium treatment in combination with the BSC arm and 84 patients were randomized to the BSC alone arm (as discussed below).Safety data. We believe that our safety and anti-tumor activity data in our two Phase 1 clinical trials, our Phase 2 clinical trial, and our partiallycompleted Phase 3 clinical trial support further development of Vicinium for the treatment of SCCHN. There were no Grade 5 serious adverse events that wereconsidered by the clinical investigator to be related to Vicinium. The serious adverse events that were reported in the clinical trials of Vicinium for thetreatment of SCCHN and were considered to be possibly, probably or definitely related to treatment consisted of abnormal tumor growth, anorexia, cancerpain, decrease in red blood cells, difficulty swallowing, elevated calcium levels, facial pain, fatigue, high blood sugar, influenza like illness, injection sitepain, liver function abnormalities, low albumin level, low sodium concentration, nausea, rash, swelling, tumor hemorrhage and tumor necrosis.Seven patients died during the clinical trials of Vicinium for the treatment of SCCHN, but none of the deaths were deemed to be related to Vicinium.Eleven patients discontinued treatment due to liver function test abnormalities; however, the serum levels were transient and they eventually returned tobaseline without any evidence of permanent liver damage. Four patients withdrew from the clinical trials. Three of the four patients withdrew at their requestand one of the four patients withdrew at the request of the investigator.Vicinium in Combination with Checkpoint Inhibitor Proposed SCCHN Phase 1/2a Clinical Trial PlanWe intend to initiate a Phase 1/2a clinical trial that will explore the potential of Vicinium in combination with a checkpoint inhibitor for thetreatment of SCCHN and are actively seeking partners for a combination program. We anticipate that the Phase 1/2a clinical trial will explore the potentialfor Vicinium, due to its potential immunogenic effect, to enhance checkpoint inhibitors in combination therapy for the treatment of SCCHN.Overall, we believe that our efficacy and safety data support the continued clinical development of Vicinium to fulfill a significant unmet medicalneed in patients with late-stage SCCHN.We have deferred further development of Vicinium for the treatment of SCCHN in order to focus our efforts and our resources on our ongoingdevelopment of Vicinium for the treatment of high-risk NMIBC. We are also exploring collaborations for Vicinium for the treatment of SCCHN.Potential future indicationsBased on the safety and efficacy data in our two Phase 1 clinical trials, our Phase 2 clinical trial and our previous partially completed Phase 3clinical trial of Vicinium for the treatment of SCCHN, we also believe that there are several other potential applications for Vicinium that we may elect topursue, including colon, thyroid and prostate cancers.VB6-845dOverviewOur lead systemically-administered product candidate, VB6-845d, is being developed as a treatment for multiple types of EpCAM-positive solidtumors. VB6-845d is a TFPT consisting of an EpCAM targeting Fab genetically linked to deBouganin, which is administered by intravenous infusion.EpCAM is over-expressed on the cell surface of many solid tumors, including breast, colorectal, gastric, lung, ovarian and prostate. EpCAM overexpressionhas been shown to be involved in promoting malignant progression. In addition, EpCAM overexpression is associated with increased tumor grade, diseaseprogression, increased proliferative phenotypes and diminished survival. EpCAM is also a cancer stem cell marker. A Phase 1 clinical trial conducted withVB6-845, the prior version of VB6-845d, revealed no clinically relevant immune response to the deBouganin payload, and five of seven patients (71.4%)maintained stable disease (meaning no change in tumor size from baseline) after one completed cycle of treatment (four weeks) two patients had decreases intarget tumor size, and one subject who continued treatment through a third cycle (12 weeks) maintained stable disease. Interim safety data from our Phase 124Table of Contentsclinical trial was consistent with expectations for the study population of patients with advanced solid tumors and the anticipated effects of targetedbiological therapies containing immunogenic sequences.Based upon the hypersensitivity reactions seen in our Phase 1 clinical trial conducted in Russia and in the country of Georgia, we de-immunized theFab portion of VB6-845 to create VB6-845d. In April 2016, we submitted an IND to the FDA in preparation of initiating a Phase 1/2 clinical trial of VB6-845d in patients with EpCAM-positive cancers in the United States. The IND was withdrawn in July 2016 after we received initial feedback from the FDAindicating that they had identified hold and non-hold deficiencies that needed to be addressed. In December 2016, we submitted a request for a pre-INDmeeting to seek input on the manufacturing, nonclinical and clinical plans for VB6-845d prior to resubmitting an IND. In February 2017, the FDA providedguidance on our manufacturing and nonclinical plans for VB6-845d. Based on this guidance, we are performing additional studies and we plan on submittingan updated IND, once funding or a partner is secured for this program.Overall, we believe that our pre-clinical data and the interim Phase 1 clinical data support further clinical investigation of VB6-845d to explorewhether it may fulfill the significant unmet medical need in the treatment of patients with EpCAM-positive solid tumors. Specifically, we believe that VB6-845d has potential to be a first-in-class TFPT capable of providing clinical benefit in these difficult to treat patient populations.We are currently developing VB6-845d, a recombinant fusion protein consisting of an anti-EpCAM fragment fused to a deBouganin payload for thesystemic treatment of advanced solid tumors. DeBouganin acts by inhibiting protein synthesis and helps circumvent multi-drug resistance mechanisms. Solidtumors form an abnormal and discrete tumor mass in the body that usually does not contain cysts or liquid areas.We believe that our TFPTs utilizing our de-immunized deBouganin payload may be enhanced if combined with checkpoint inhibitors. We believethat deBouganin’s potential effect on cancer cells could promote an immunogenic response that may enhance the action of checkpoint inhibitors.We have deferred further development of VB6-845d in order to focus our efforts and our resources on our ongoing development of Vicinium for thetreatment of high-risk NMIBC. We are also exploring collaborations for VB6-845d.We own or exclusively license worldwide rights to our VB6-845d intellectual property portfolio that provides unextended patent term until at leastJune 2025 and, if our pending composition of matter patent applications for VB6-845d are granted until at least 2036. See ‘‘Business-Intellectual Property’’for additional details.Clinical trials and pre-clinical studiesPre-clinical studies. VB6-845, the prior version of VB6-845d, demonstrated strong binding and potent activity with small doses of the productcandidate against numerous EpCAM-positive solid tumor cell lines, including those derived from tumors of the breast, cervix, colon, endometrium, gastric,lung and ovary, in in vitro pharmacology studies. In vitro and in vivo pre-clinical data have also demonstrated that VB6-845 preferentially binds to tumorcells expressing EpCAM and is effective in inhibiting tumor growth and increasing survival in mouse models. These xenograft studies demonstrated thatVB6-845 was able to selectively affect EpCAM-expressing tumors without observed systemic toxicity.Phase 1 clinical trial. We received regulatory approval from the Federal Service on Surveillance in Healthcare and Social Development of theRussian Federation (Roszdravnadzor) to conduct a Phase 1 clinical trial in Russia in March 2007 and from Ministry of Labour Health and Social Affairs ofGeorgia in April 2007. We initiated an open-label Phase 1 clinical trial of VB6-845 in May 2007 at five sites in Russia and one site in Georgia. We enrolled15 patients with EpCAM-positive solid tumors, including breast, colorectal, kidney, non-small cell lung, ovary, pancreas and stomach cancers. All patientsenrolled in this Phase 1 clinical trial had tumors that tested positive for EpCAM as confirmed by our immunohistochemical test used during this Phase 1clinical trial of VB6-845. The Phase 1 clinical trial was designed to define the maximum tolerated dose and to evaluate immunogenicity, safety. Secondaryobjectives included information on PK properties and assessing exploratory efficacy of VB6-845.Patients were treated over three dose cohorts in this Phase 1 clinical trial. VB6-845 was administered as a monotherapy intravenous infusion (for aperiod of over three hours), once weekly in four-week cycles, to patients with EpCAM-positive advanced solid tumors. Patients were evaluated at the end ofeach cycle. Three patients at the first cohort dose level received 1.00 mg/kg, 10 patients at the second cohort dose level received 2.00 mg/kg and two patientsat the third cohort dose level received 3.34 mg/kg. Following treatment of the patients in the second cohort, the clinical reporting company reviewed thesafety data and unanimously decided to escalate to the third cohort at a dose of 3.34 mg/kg. Out of the first group of five patients in the second cohort, oneDLT (an infusion-related reaction) was reported and confirmed by the clinical trial25Table of Contentsmonitoring company. As the study was stopped early, no maximum tolerated dose was reached. VB6-845 was generally well-tolerated up to the third dosecohort (3.34 mg/kg).One of our primary objectives in this Phase 1 clinical trial was to validate the extensive pre-clinical data supporting de-immunization of thedeBouganin cytotoxic protein payload in humans. For a payload to be viable systemically it must be de-immunized to prevent rapid clearance by theimmune system. Subject blood samples for the assessment of an anti-VB6-845 response were collected pre-infusion for the first cycle and every four weeksthereafter. An analysis of the antibody titers at each time point revealed a minimal immune response directed against the deBouganin payload for only twopatients after eight weeks. Moreover, the titer of the immune response was just above the threshold of the assay (ranging between a titer of 1500 to 1800).These findings are consistent with significant de-immunization of the parent Bouganin cytotoxic protein payload via T-cell epitope depletion.For all cohorts, exploratory efficacy data (CT and radiographic) were available for seven patients who completed one full cycle (four weeks) oftreatment. Five of the seven patients showed stable disease, which means tumor measurement is unchanged relative to baseline, on CT scans one week afterthe completion of a fourth dose of VB6-845. Of the three patients who continued to receive treatment past the first cycle, one patient continued to have stabledisease at the completion of their second (eight weeks) and third (12 weeks) cycles. There was radiographic evidence of decreases in tumor size in twopatients with renal cell carcinoma and breast carcinoma. For one subject, six measurable target tumors in the lungs as well as a measurable target tumor in apulmonary lymph node and pelvic mesentery showed decreases by CT scan ranging from 11% to 29% on a final visit relative to the baseline. Other non-target, non-measurable tumors appeared unchanged; although there was an appearance of disease progression as a potentially new brain tumor, which wasinaccessible to treatment. In one other subject, CT scan results revealed decreases in four of the five measurable target tumors in the liver, with decreases inindividual tumors ranging from 4% to 15%. Non-target, non-measurable tumors in lungs, liver and bones showed stable disease.This Phase 1 clinical trial was terminated in April 2008. Patients in this Phase 1 clinical trial exhibited little to no immune responses to thedeBouganin payload, thereby demonstrating de-immunization of deBouganin. Patients did, however, generate antibodies against the Fab molecule in theproduct candidate, specifically against mouse amino acid sequences that were left in the Fab to increase the thermal stability in this early version of themolecule. Taken together, we believe this demonstrated that the patients were fully immunocompetent, which means that they were capable of rejecting thedeBouganin payload if their immune system recognized it as foreign. Furthermore, it is important to note that the deBouganin payload was presented to thepatients’ immune system as a fusion with the immunogenic Fab fragment. The ‘‘hapten-carrier effect’’ principal in immunology dictates that presenting anon-immunogenic ‘‘hapten’’ protein (deBouganin) to the immune system as a conjugate or fusion to an immunogenic ‘‘carrier’’ protein (Fab with mouseamino acid sequences) is an effective way to amplify the immunogenicity of the non-immunogenic protein. Our observation of a lack of immunogenicity ofdeBouganin in this setting is further evidence of its de-immunization. We have since engineered these mouse amino acid sequences out of VB6-845, whichwe refer to as VB6-845d, and based upon a binding specificity pre-clinical study, VB6-845d retained biologic activity.26Table of Contents The chart below demonstrates why we believe that we have successfully de-immunized VB6-845 to create VB6-845d as shown by in a Phase 1clinical trial that revealed no clinically relevant immune response to the deBouganin payload.27Table of ContentsSafety data. We believe that the interim safety data from the 15 patients in our Phase 1 clinical trial support further development of VB6-845d.There were no Grade 5 serious adverse events that were considered by the clinical investigator to be related to VB6-845. The Grade 3 and Grade 4 seriousadverse events that were reported in the Phase 1 clinical trial of VB6-845 and considered to be possibly, probably or definitely related to treatment,consisting of an infusion related reaction and an infusion site reaction that are consistent with the immunogenic nature of the Fab fragment. The patient'scondition improved and the event was considered to be resolved one day after onset without any further clinical concerns. The patient with the infusionrelated reaction was discontinued from the Phase 1 clinical trial in accordance with the protocol treatment stopping criteria defined for Grade 4 seriousadverse events. The adverse event data reported for the patients at the time the Phase 1 clinical trial was terminated was based upon interim data.VB6-845d Phase1/2 clinical trial development planIn April 2016, we submitted an IND to the FDA in preparation of initiating a Phase 1/2 clinical trial of VB6-845d in patients with EpCAM-positivecancers in the United States. The IND was withdrawn in July 2016 after we received initial feedback from the FDA indicating that they had identified holdand non-hold deficiencies that needed to be addressed. In December 2016, we submitted a request for a pre-IND meeting to seek input on themanufacturing, nonclinical and clinical plans for VB6-845d prior to resubmitting an IND. In February 2017, the FDA provided guidance on ourmanufacturing and nonclinical plans for VB6-845d. Based on this guidance, we are performing additional studies and plan on submitting an updated IND.Overall, we believe that our pre-clinical data and the interim Phase 1 clinical data support further clinical investigation of VB6-845d to explorewhether it may fulfill the significant unmet medical need in the treatment of patients with EpCAM-positive solid tumors. We also believe that thedeBouganin payload in VB6-845d may enhance the action of checkpoint inhibitors as a result of the promotion of a local tumor immune response followingthe death of cancer cells.EBI-031License Agreement with RocheOn June 10, 2016, we entered into the License Agreement with Roche. The License Agreement became effective on August 16, 2016, followingstockholder approval. Under the License Agreement, we granted Roche an exclusive, worldwide license, including the right to sublicense, to our patent rightsand know-how related to our monoclonal antibody EBI-031 or any28Table of Contentsother IL-6 antagonist anti-IL-6 monoclonal antibody, to make, have made, use, have used, register, have registered, sell, have sold, offer for sale, import andexport any product containing such an antibody or any companion diagnostic used to predict or monitor response to treatment with such a product, orcollectively, Licensed Intellectual Property.Pursuant to the terms of the License Agreement, Roche is required to continue developing EBI-031 and any other product made from the LicensedIntellectual Property that contains an IL-6 antagonist anti-IL-6 monoclonal antibody, or Licensed Product, and pursue ongoing patent prosecution, at its cost.Financial TermsRoche paid an up-front license fee of $7.5 million upon effectiveness of the license under the License Agreement, and agreed to pay up to anadditional $262.5 million upon the achievement of specified regulatory, development and commercial milestones with respect to up to two unrelatedindications. Specifically, an aggregate amount of up to $197.5 million is payable to us for the achievement of specified milestones with respect to the firstindication: consisting of $72.5 million in development milestones, $50.0 million in regulatory milestones and $75.0 million in commercializationmilestones.Roche paid the first development milestone of $22.5 million as a result of the IND application for EBI-031 becoming effective. Additional amountsof up to $65.0 million are payable upon the achievement of specified development and regulatory milestones in a second indication.In addition, we are entitled to receive royalty payments in accordance with a tiered royalty rate scale, with rates ranging from 7.5% to 15% for netsales of potential future products containing EBI-031 and up to 50% of these rates for net sales of potential future products containing other IL-6 compounds,with each of the royalties subject to reduction under certain circumstances and to the buy-out options of Roche further described below.Buy-Out OptionsThe License Agreement provides for two “option periods” during which Roche may elect to make a one-time payment to us and, in turn, terminateits diligence, milestone and royalty payment obligations under the License Agreement. Specifically, (i) Roche may exercise a buy-out option following thefirst dosing, or Initiation, in the first Phase 2 study for a Licensed Product until the day before Initiation of the first Phase 3 study for a Licensed Product, inwhich case Roche is required to pay us $135.0 million within 30 days after Roche’s exercise of such buy-out option and receipt of an invoice from us, or (ii)Roche may exercise a buy-out option following the day after Initiation of the first Phase 3 study for a Licensed Product until the day before the acceptancefor review by the FDA or other regulatory authority of a biologics license application, or BLA, or similar application for marketing approval for a LicensedProduct in either the United States or in the E.U. in which case Roche is required to pay us, within 30 days after Roche’s exercise of such buy-out option andreceipt of an invoice from us, $265.0 million, which amount would be reduced to $220.0 million if none of our patent rights containing a composition ofmatter claim covering any compound or Licensed Product has issued in the E.U.TerminationEither we or Roche may each terminate the License Agreement if the other party breaches any of its material obligations under the LicenseAgreement and does not cure such breach within a specified cure period. Roche may terminate the License Agreement following effectiveness by providingadvance written notice to us or by providing written notice if we are debarred, disqualified, suspended, excluded, or otherwise declared ineligible fromcertain federal or state agencies or programs. We may terminate the License Agreement if, prior to the first filing of a BLA for a Licensed Product, there is aperiod of 12 months where Roche is not conducting sufficient development activities with respect to the products made from the Licensed IntellectualProperty.Intellectual propertyWe currently own or exclusively license approximately 17 families of patents and applications, which generally relate to our TFPT-based productcandidates and evolving our platform of targeting agents, cytotoxins (such as deBouganin) and linker technologies. As our product candidates evolvethrough clinical development, we continue to monitor advancements and bolster patent coverage with the goal of attaining durable patent protection for atleast 15 years from product launch. In addition, we may prepare and file a number of additional applications around our platform technology, including ourvarious targeting agents, cytotoxins, and linkers that, if issued, would expire in 2038 and beyond.Product Candidate -Vicinium29Table of ContentsWe exclusively license two families (70 patents and 3 applications) from the University of Zurich, or Zurich, which, among other things, includecomposition of matter claims directed to EpCAM antibody chimeras, EpCAM antibody chimera-cytotoxin conjugates, and their potential use in treatingbladder and head and neck cancer. These families claim all or portions of Vicinium, as well as certain of their respective indications under clinicaldevelopment. The first family includes composition of matter claims directed to the EpCAM antibody chimeras that are used in Vicinium. The first familyconsists of 21 patents in the United States, Canada, Europe and Japan, which expire in April 2020, subject to any applicable patent term adjustment orextension that may be available on a jurisdictional basis. The second family includes claims directed to the use of Vicinium in the treatment of bladder andhead and neck cancer, respectively, and consists of 49 issued patents in the United States, Europe, Canada, China, Israel and Japan and pending applicationsin the United States, Canada, and Hong Kong. The expiry date of the patents in this family is April 2024, subject to any applicable patent term adjustment orextension that may be available on a jurisdictional basis.In addition to the Zurich portfolio, we own one issued U.S. patent with composition of matter claims directed to modified nucleic acid sequencesthat encode Vicinium and are potentially useful for high expression yield of Vicinium. The expiry date of this patent is in February 2029, subject to anyapplicable patent term extension that may be available on a jurisdictional basis. In addition, we have filed and may prepare and file a number of additionalpatent applications with claims around composition of matter, manufacturing and purification methods, medical applications, and various uses of our variousproduct candidates that, if issued, would expire in 2036 and beyond.Additionally, we have a license agreement with Micromet AG, or Micromet, now part of Amgen, Inc., which grants us non-exclusive rights, withcertain sublicense rights, for know-how and patents allowing exploitation of certain single chain antibody products. These patents cover some key aspects ofVicinium.We also have a license agreement with XOMA Ireland Limited, or XOMA, which grants us non-exclusive rights to certain XOMA patent rights andknow-how related to certain expression technology, including plasmids, expression strains, plasmid maps and production systems. These patents and relatedknow-how cover some key aspects of Vicinium.Bouganin and deBouganin familyWe exclusively license a family of patents and applications licensed from Merck KGaA, or Merck, which include claims directed to, among otherthings, modified de-immunized bouganin protein, EpCAM antibody-bouganin conjugates, and use claims directed to, among other things, methods of usingthe same to treat various diseases, including cancer. Claims in this family may cover, among other things, both the immunoconjugate, VB6-845d, and the de-immunized bouganin cytotoxins used in our product candidates. Currently the family consists of three issued patents in the United States, as well as 30issued patents in Australia, Canada, China, Europe, Hong Kong, India, Israel, Japan, South Korea, Mexico, New Zealand, Russia and South Africa and onepending application in Brazil. The expiry date of this family is in March 2025, subject to any applicable patent term adjustment or extension that may beavailable on a jurisdictional basis. We also exclusively license from Merck three additional families of patents and applications with, among other things, useclaims directed to various de-immunization methodologies, which expire in May 2018, December 2018 and February 2022, subject to any applicable patentterm adjustment or extension that may be available on a jurisdictional basis. In addition, we have filed and may prepare and file a number of additionalpatent applications with, among other things, composition of matter and use claims around our various product candidates that, if issued, would expire in2036 and beyond.We also exclusively license a family of patents directed to the unmodified bouganin cytotoxin from Protoden Technologies Inc., or Protoden, acompany owned by Clairmark Investments Ltd., or Clairmark. See ‘‘See ‘‘Board Policies-Related Party Transactions’’ for additional details. The two UnitedStates patents expire in June 2018, subject to any applicable patent term adjustment or extension that may be available on a jurisdictional basis. We do notcurrently view these patents and applications as significant to the development and commercialization, if approved, of our product candidates.EBI-031 and our Legacy Product CandidatesAs of February 28, 2019, we owned the following families of patents and patent applications related to EBI-031 and our legacy product candidates,including EBI-005, or isunakinra. As of February 28, 2019, our patent portfolio includes the following patents and applications related to our legacy productcandidates:•a United States, a New Zealand, Japan, Taiwan, China and a South Africa composition of matter patent covering isunakinra which expires in 2031;30Table of Contents•composition-of-matter patent applications covering isunakinra in Australia, Brazil, Canada, China, Europe, Hong Kong, India, Israel, Korea, Mexicoand Russia, which, if granted, are expected to expire in 2031;•patent applications covering the formulation of isunakinra filed in the United States, Australia, Canada, China, Europe, Hong Kong, Japan, NewZealand, Russia, and Singapore, which, if granted, are expected to expire in 2034;•a patent application covering the formulation of isunakinra in a blow fill seal container filed in Taiwan, which if granted, is expected to expire in2035;Additional families of patent applications owned by us include:•a provisional application directed to compositions and methods for increasing the retention of therapeutic agents in the eye which, if converted andgranted, is expected to expire in 2038.•a provisional application directed to compositions and methods for increasing the retention of anti-VEGF therapeutic agents in the eye which, ifconverted and granted, is expected to expire in 2038; and•a provisional application directed to compositions and methods for increasing the retention of RGD therapeutic agents in the eye which, ifconverted and granted, is expected to expire in 2038To the best of our knowledge based on correspondence received prior to April 21, 2017, the following families are owned by us, and licensed toRoche pursuant to the License Agreement dated June 10, 2016:•patent applications covering the IL-6 antagonistic anti-IL6 monoclonal antibodies and active fragments thereof, including IL-6 antibody EBI-029,filed in the United States, Australia, Brazil, Canada, China, Europe, Hong Kong, India, Israel, Japan, Korea, Mexico, New Zealand, Russia,Singapore, and South Africa, and, if granted, are expected to expire in 2033;•patent applications covering IL-6 antagonistic anti-IL6 monoclonal antibodies and active fragments thereof, including the IL-6 antibody EBI-031,having a pending PCT application and applications pending or to be filed in Algeria, Australia, Bahrain, Brazil, Canada, Chile, Colombia, CostaRica, Egypt, Europe (to be filed), India, Israel, Korea, Malaysia, Mexico, Morocco, New Zealand, Oman, Philippines, Qatar, Russian Federation,Saudi Arabia, Singapore, South Africa, Thailand, Ukraine, United Arab Emirates, and Vietnam, and, if granted are expected to expire in 2035; and•a PCT Application and an Argentine application each corresponding to a United States provisional application covering the IL-6 antibody EBI-031formulation, which if granted, are expected to expire in 2036.License AgreementsLicense Agreement with the University of ZurichOverview and Exclusivity. We have a license agreement with the University of Zurich, or Zurich, which grants us exclusive license rights, with theright to sublicense, to make, have made, use and sell under certain patents primarily directed to our targeting agent, including an EpCAM chimera and relatedimmunoconjugates and methods of use and manufacture of the same. These patents cover some key aspects of our product candidate Vicinium.Under the terms of the agreement, we may be obligated to pay $750,000 in milestone payments, for the first product candidate that achieves applicableclinical development milestones. Based on current clinical status, we anticipate that these milestones may be triggered by Vicinium’s clinical developmentpathway. As part of the consideration, we will also be obligated to pay up to a 4% royalty on the net product sales for products covered by or manufacturedusing a method covered by a valid claim in the Zurich patent rights. Royalties owed to Zurich will be reduced if the total royalty rate owed by us to Zurichand any other third party is 10% or greater, provided that the royalty rate to Zurich may not be less than 2% of net sales. The obligation to pay royalties in aparticular country expires upon the expiration or termination of the last of the Zurich patent rights that covers the manufacture, use or sale of a product. Thereis no obligation to pay royalties in a country if there is no valid claim that covers the product or a method of manufacturing the product. As of the date of thisAnnual Report on Form 10-K, aggregate license fees of $300,000 have been paid to Zurich since the inception of the license agreement. There were nopayments made for the year ended December 31, 2018.Patent rights. We are responsible for the patent filing, prosecution and maintenance activities pertaining to the patent rights, at our sole expense,while Zurich is afforded reasonable opportunities to review and comment on such activities. If appropriate, we shall apply for an extension of the term of anylicensed patent where available, for example, in at least the United States, Europe and Japan. In the event of any substantial infringement of the patent rights,we may request Zurich to take action to enforce the licensed patents against third parties. If the infringing activity is not abated within 90 days and Zurichhas elected not to take legal action, we may bring suit in our own name (and in Zurich’s name, if necessary). Such action will31Table of Contentsbe at our own expense and Zurich will have the opportunity to join at its own expense. Recoveries from any action shall generally belong to the partybringing the suit, but (a) in the event that we bring the action and an acceptable settlement or monetary damages are awarded, then Zurich will be reimbursedfor any amount that would have been due to Zurich if the products sold by the infringer actually had been sold by us, or (b) in the event a joint legal action isbrought, then the parties shall share the expense and recoveries shall be shared in proportion to the share of expense paid by the respective party. Each partyis required to cooperate with the other in litigation proceedings at the expense of the party bringing the action.Term and termination. The term of the agreement expires as of the expiration date of the last patent to expire within the Zurich patent rights. We arecurrently projecting an expiration date for the U.S. licensed patents in June 2025, subject to any applicable patent term extension that may be available on ajurisdictional basis. Zurich has the right to terminate the agreement if we breach any obligation of the agreement and fail to cure such breach within theapplicable cure periods. We have the right to terminate the agreement at any time and for any reason by giving 90 days written notice to Zurich.License Agreement with MicrometOverview. We have a license agreement with Micromet AG, or Micromet, now part of Amgen, Inc., which grants us nonexclusive rights, with certainsublicense rights, for know-how and patents allowing exploitation of certain single chain antibody products. These patents cover some key aspects ofVicinium. Under the terms of the agreement, an initial license fee of €450,000 was paid to Micromet by Viventia prior to our acquisition of Viventia and wemay be obligated to pay up to €3.6 million in milestone payments, for the first product candidate that achieves applicable clinical development milestones.Based on current clinical status, we anticipate that certain of these milestones may be triggered by Vicinium’s clinical development pathway. We are alsorequired to pay up to a 3.5% royalty on the net sales for products covered by the agreement, which includes Vicinium. The royalty rate owed to Micromet in aparticular country will be reduced to 1.5% if there are no valid claims covering the product in that country. The obligation to pay royalties in a particularcountry expires upon the later of the expiration date of the last valid claim covering the product and the tenth anniversary of the first commercial sale of theproduct in such country. Finally, we are required to pay to Micromet an annual license maintenance fee of €50,000, which can be credited towards anyroyalty payment we owe to Micromet. As of the date of this Annual Report on Form 10-K, aggregate license fees of €1.75 million have been paid toMicromet. We paid €50,000 in annual license maintenance fees during each of the years ended December 31, 2018 and 2017.Patent rights. Micromet, at its sole expense, is responsible for the patent filing, prosecution and maintenance activities pertaining to the patent rights. In anypatent enforcement action initiated by Micromet, we may be required, upon the request of Micromet and at Micromet’s expense, to provide reasonableassistance to Micromet with respect to such enforcement action.Term and termination. The term of the license agreement expires as of the expiration of any royalty obligations under the license agreement. Either party hasthe right to terminate the agreement if the other party fails to comply with any of its material obligations under the license agreement and fails to cure suchnon-compliance within the applicable cure periods.License Agreement with XOMAOverview. We have a license agreement with XOMA Ireland Limited, or XOMA, which grants us non-exclusive rights to certain XOMA patent rights andknow-how related to certain expression technology, including plasmids, expression strains, plasmid maps and production systems. These patents and relatedknow-how cover some key aspects of Vicinium. Under the terms of the agreement, an initial access fee of $250,000 was paid to XOMA by Viventia prior toour acquisition of Viventia and we are required to pay up to $250,000 in milestone payments for a product candidate that incorporates know-how under thelicense and achieves applicable clinical development milestones. Based on current clinical status, we anticipate that these milestones may be triggered byVicinium’s clinical development pathway. We are also required to pay a 2.5% royalty on the net sales for products incorporating XOMA’s technology, whichincludes Vicinium. We have the right to reduce the amount of royalties owed to XOMA on a country-by-country basis by the amount of royalties paid toother third parties, provided that the royalty rate to XOMA may not be less than 1.75% of net sales. In addition, the foregoing royalty rates are reduced by50% with respect to products that are not covered by a valid patent claim in the country of sale. The obligation to pay royalties in a particular country expiresupon the later of the expiration date of the last valid claim covering the product and the tenth anniversary of the first commercial sale of the product in suchcountry. As of the date of this Annual Report on Form 10-K, aggregate license fees of $400,000 have been paid to XOMA since the inception of the licenseagreement. There were no payments made for the year ended December 31, 2018.Patent rights. XOMA, at its sole expense, is responsible for the patent filing, prosecution and maintenance activities pertaining to the patent rights. In anypatent enforcement action initiated by XOMA, we may be required, upon the request of XOMA and at XOMA’s expense, to provide reasonable assistance toXOMA with respect to such enforcement action.32Table of ContentsTerm and termination. The term of the agreement expires as of the expiration of any royalty obligations under the license agreement. Either party has theright to terminate the agreement if the other party fails to comply with any of its material obligations under the license agreement and fails to cure such non-compliance within the applicable cure periods.License Agreement with Merck KGaAOverview and exclusivity. In March 2004, we entered into an exclusive license agreement with Biovation Limited, subsequently acquired by Merck,which was subsequently amended and restated in October 2015. Pursuant to the agreement, we were granted an exclusive license, with the right to sublicense,under certain patents and technology relating to the de-immunization of our cytotoxin Bouganin for therapeutic and in vivo diagnostic purposes in humans.The de-immunized cytotoxin is known as deBouganin, and has been incorporated into our product candidate, VB6-845d. We have the worldwide exclusiveright, with the right to sublicense, under the licensed patents and technology to, among other things, make, have made, use or sell products incorporatingdeBouganin.As of the date of this Annual Report on Form 10-K, aggregate license fees of $225,000 have been paid to Merck by Viventia prior to our acquisitionof Viventia. There were no payments made for the year ended December 31, 2018. Under the agreement, we may be obligated to pay certain clinicaldevelopment and regulatory milestones for each ‘‘licensed product’’: (A) $2,000,000 upon the start of the first Phase 3 clinical trial for a licensed product; (B)$2,000,000 upon submission of the first BLA for a licensed product; (C) $2,000,000 upon the approval of the first BLA in certain countries for a licensedproduct and $1,000,000 upon each of the second and third approvals of a BLA in certain additional countries for the same licensed product (total of$4,000,000); and (D) $2,000,000 upon the approval of the second BLA in certain countries for a licensed product; and $1,000,000 upon each of the secondand third approvals of the second BLA in certain additional countries for the same licensed product (total of $4,000,000). As part of the consideration, we areobligated to pay a 1.5% royalty on the net product sales up to $150,000,000 and a 2% royalty on the net product sales above such amount.Patent rights. We have the first right to file, prosecute and maintain licensed patents relating to de-immunized plasmids and proteins, including,among other things, our deBouganin and Merck has the first right to file, prosecute and maintain any other licensed patents. We have the first right, but notthe obligation, to enforce the licensed patents against third parties for suspected infringement, and, after repayment of costs and expenses, any recoveriesunder such suit will be treated as net product sales and we shall pay a royalty on the same. We may not settle such patent infringement suit without the priorwritten consent of Merck, but such consent shall not be unreasonably delayed or withheld. If we decline to enforce the licensed patents against third partiesfor suspected infringement, Merck may bring such a patent infringement suit and any recoveries will be retained by Merck.Term and termination. The agreement expires on a country-by-country and product-by-product basis until the longer of (i) the expiration of the lastto expire patent within the licensed patent rights that covers a licensed product and (ii) 10 years from the first commercial sale of a licensed product in suchcountry; provided that no royalty is payable for more than 15 years from the first commercial launch of a licensed product anywhere in the world. Either partyhas the right to terminate the agreement for breach of the agreement and if the other party fails to cure such breach within the applicable cure period. We havethe right to terminate the agreement by giving Merck six months prior written notice.ManufacturingWe maintain an approximately 31,100 square foot manufacturing, laboratory, warehouse and office facility in Winnipeg, Manitoba, Canada. Wehave three 15 liter fermenters, one 150 liter fermenter, one 500 liter fermenter and one 1,500 liter fermenter. Our classified fermentation suite and post-production processing capabilities were dedicated to producing our pre-clinical study and clinical trial batches. In September 2017, we completed themanufacturing of all Vicinium necessary for our ongoing Phase 3 registration trial in patients with NMIBC, and for our CRADA with the NCI. In conjunctionwith this achievement, we ended our large-scale manufacturing activities and redirected resources toward completing our Phase 3 trial. In the event we obtainapproval from the FDA to market any of our product candidates, we will need to outsource our commercial scale manufacturing to contract manufacturingorganizations, or CMOs.On October 4, 2018, we entered into the Fujifilm MSA, pursuant to which Fujifilm will provide certain manufacturing services related to Vicinium.The Fujifilm MSA is designed to facilitate a transfer of certain of our manufacturing processes and technologies from us to Fujifilm to determine if Fujifilmcan develop the bulk drug substance form of Vicinium for commercial purposes if we receive regulatory approval to market Vicinium for the treatment ofhigh-risk NMIBC.Commercial Operations33Table of ContentsWe do not currently have an organization structured for the sales, marketing and distribution of products. We may rely on licensing and co-promotion agreements with strategic collaborators for the commercialization of our products in the United States and other territories. If we choose to build acommercial infrastructure to support marketing in the United States, such commercial infrastructure could be expected to include a sales force supported bysales management, internal sales support, an internal marketing group and distribution support. To develop the appropriate commercial infrastructureinternally, we would have to invest financial and management resources, some of which would have to be deployed prior to the approval of any of ourproduct candidates.CompetitionThe pharmaceutical industry is highly competitive, subject to rapid and significant technological change and has a strong emphasis on developingproprietary products. While we believe that our next generation TFPT platform, knowledge, experience and scientific resources provide us with competitiveadvantages, we face competition from both large and small pharmaceutical and biotechnology companies, academic institutions and other researchorganizations; specifically with companies, institutions and organizations that are actively researching and developing products that attach proprietary cell-killing payloads to antibodies for targeted delivery to cancer cells. Our competitors include, but are not limited to:•NMIBC: Aadi, LLC (ABI-009), Altor Bioscience Corporation (ALT-801), Cold Genesys, Inc. (CG0070), Merck (Keytruda/pembroluzumab), EndoPharmaceuticals Inc. (Valstar) (approved drug), FKD Therapies Oy (Instilidrin), Merck and other pharmaceutical companies (BCG) (approved drug),Eli Lilly and Company (Gemcitabine), Telormedix SA (Vesimune) and Anchiano Therapeutics Ltd. (inodiftagene vixteplasmid);•SCCHN: Bristol-Myers Squibb Company (nivolumab)(approved drug), Eli Lilly and Company, and Merck (Erbitux, pembrolizumab) (approveddrugs);•Multiple types of solid tumors: Amgen Inc. (Panitumumab) (approved drug), Bayer AG and Onyx Pharmaceuticals (Sorafenib) (approved drug),Bristol-Myers Squibb Company, Eli Lilly and Company, and Merck (Erbitux) (approved drug), F. Hoffmann-La Roche AG (Bevacizumab)(approved drug), Genentech, Inc. (Bevacizumab, Erlotinib and Trastuzumab) (approved drugs), Pfizer, Inc. (Sunitinib) and Trion Research GmbH(Removab); and•In addition to competition from alternative treatments, we may also face competition from products that are biosimilar to, and possiblyinterchangeable with, our product candidates. Biosimilar products are expected to become available over the coming years. Even if our productcandidates achieve marketing approval, they may be priced at a significant premium over competitive biosimilar products if any have beenapproved by then and insurers or other third party payors may encourage or even require the use of lower priced biosimilar products. Even if ourtreatments receive market authorization, they may not be listed on the formularies of payors (public or private insurers) or reimbursed. This mayimpact the uptake of the drug as a treatment option for patients and/or the price at which the drug can be sold at. Further, if the drug is reimbursed itmay be at a narrower indication than the full scope of market authorization.Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, pre-clinicalstudies, conducting clinical trials, obtaining regulatory approval and marketing than we do. These competitors are also active in seeking patent protectionand licensing arrangements in anticipation of collecting royalties for use of technology that they have developed. Moreover, specialized biologics,biopharmaceutical and biotechnology companies may prove to be significant competitors, particularly through collaborative arrangements with large andestablished companies.Our commercial opportunity could be substantially limited in the event that our competitors develop and commercialize products that are moreeffective, safer, less toxic, more convenient or cheaper than our comparable products. In geographies that are critical to our commercial success, competitorsmay also obtain regulatory approvals before us, resulting in our competitors building a strong market position in advance of our product’s entry. We believethe factors determining the success of our programs will be the drug design, effectiveness against multi-drug resistance mechanisms, efficacy, safety, price andconvenience of our product candidates.Government RegulationAs a clinical-stage biologics company, we are subject to extensive regulation by the FDA, Health Canada and other national, supranational, state,provincial and local regulatory agencies. We are also subject to extensive regulation by similar governmental authorities in other countries in which weoperate. In the United States, the Federal Food, Drug, and Cosmetic Act, or the FDCA, and the Public Health Service Act, or PHSA, and their implementingregulations set forth, among other things, requirements for the research, testing, development, manufacture, quality control, safety, effectiveness, approval,post-approval monitoring and reporting, labeling, storage, record keeping, distribution, import, export, advertising and promotion of our product candidates.Although the discussion below focuses on regulation in the United States, we anticipate seeking34Table of Contentsapproval to market our products in other countries. Generally, our activities in other countries will be subject to regulation that is similar in nature and scopeto that imposed in the United States, although there can be important differences. Additionally, some significant aspects of regulation in the E.U. areaddressed in a centralized way through the European Commission following the opinion of the EMA, but country-specific regulation in the individualEuropean Union Member States, or the E.U. Member States, remains essential in many respects. The process of obtaining regulatory marketing approvals andthe subsequent compliance with appropriate supranational, federal, state, provincial, local and foreign statutes and regulations require the expenditure ofsubstantial time and financial resources, and we may not be successful in any given jurisdiction.U.S. Government RegulationIn the United States, drug products are regulated by the FDA under the FDCA and other laws, including, in the case of biologics, the PHSA. Drugproducts are also subject to other federal, state and local statutes and regulations. A failure to comply with any applicable requirements during the productdevelopment, approval, or post-approval periods may lead to administrative or judicial sanctions, including, among other things, the imposition by the FDAor an institutional review board, or IRB, of a hold on clinical trials, refusal to approve pending marketing applications or supplements, withdrawal ofapproval, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, or administrative, civiland/or criminal investigation, penalties or prosecution.In the United States, all of our product candidates are regulated by the FDA as biologics. Biologics require the submission of a BLA, and approvalby the FDA prior to being marketed in the United States. Manufacturers of biologics may also be subject to state and local regulation.The steps required before a biologic may be marketed in the United States generally include:•completion of pre-clinical studies, animal studies and formulation studies, some in compliance with the FDA’s Good Laboratory Practices, orGLP, regulations, and the Animal Welfare Act administered and enforced by the U.S. Department of Agriculture;•submission to the FDA of an IND to support human clinical testing, which must become effective before human clinical trials may commence;•approval by an IRB before each trial may be initiated at each clinical site;•performance of adequate and well-controlled clinical trials under protocols submitted to FDA and reviewed and approved by each IRB,conducted in accordance with federal regulations and current Good Clinical Practices, or GCPs, to establish the safety, purity and potency of thebiologic for each targeted indication;•submission of a BLA to the FDA;•satisfactory completion of an FDA Advisory Committee review, if applicable;•satisfactory completion of an FDA inspection of the manufacturing facilities at which the biologic is produced to assess compliance with currentGood Manufacturing Practices, or cGMP, and to assure that the facilities, methods and controls are adequate; and•FDA review and approval of the BLA.Pre-clinical studiesPre-clinical studies include laboratory evaluation of product chemistry, formulation and toxicity, as well as animal studies to assess thecharacteristics and potential safety and efficacy of the product candidate. The conduct of the pre-clinical studies must comply with federal regulations andrequirements, including, as applicable, GLP and the Animal Welfare Act. The results of the pre-clinical studies, together with manufacturing information andanalytical data, are submitted to the FDA as part of an IND. The FDA evaluates the IND to determine whether there is an adequate basis for starting the drug ininitial clinical studies, and the IND must become effective before human clinical trials may be commenced. Additional pre-clinical studies may continue afterthe IND is submitted. A 30-day waiting period after the submission of each IND is required prior to the commencement of clinical testing in humans. If duringthis 30-day period the FDA does not raise any concerns or issues that must be addressed prior to the commencement of clinical trials or does not impose aclinical hold, the IND becomes effective 30 days following the FDA’s receipt of the IND and the clinical trial proposed in the IND may begin.Clinical trials35Table of ContentsClinical trials involve the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators.Clinical trials are subject to extensive regulation and must be conducted in compliance with (i) federal regulations, (ii) GCP standards, which set safeguardsto protect the rights and health of patients and establish standards for conducting, recording data from, and reporting results of clinical trials, and (iii)protocols detailing the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated, if any. Foreignstudies conducted under an IND generally must meet the same requirements that apply to studies being conducted in the United States. The informed writtenconsent of each study patient must be obtained before the patient may begin participation in the clinical trial. The study protocol, study plan, and informedconsent forms for each clinical trial must be reviewed and approved by an institutional review board, or IRB, for each clinical site, and the study must beconducted under the auspices of an IRB for each trial site. Investigators and IRBs must also comply with FDA regulations and guidelines, including thoseregarding oversight of study patient informed consent, complying with the study protocol and investigational plan, adequately monitoring the clinical trial,and timely reporting of adverse events.The clinical trial program for a product candidate is generally divided into three phases. Although the phases are usually conducted sequentially, they mayoverlap or be combined. The three phases are as follows:•Phase 1. Phase 1 involves the initial introduction of a product candidate into humans. Phase 1 clinical trials are typically conducted in healthyhuman patients, but in some situations are conducted in patients with the target disease or condition. These clinical trials are generally designed toevaluate the safety, metabolism, PK properties and pharmacologic actions of the product candidate in humans, the side effects associated withincreasing doses and, if possible, to gain early evidence on effectiveness. During Phase 1 clinical trials, sufficient information about the productcandidate’s PK properties and pharmacological effects may be obtained to inform and support the design of Phase 2 clinical trials. The total numberof participants included in Phase 1 clinical trials varies, but is generally in the range of 20 to 80;•Phase 2. Phase 2 includes the controlled clinical trials conducted to obtain initial evidence of effectiveness of the product candidate for a particularindication(s) in patients with the target disease or condition, to determine dosage tolerance and optimal dosage, gather additional information onpossible adverse side effects and safety risks associated with the product candidate. Phase 2 clinical trials are typically well-controlled, closelymonitored, and conducted in a limited patient population, usually involving no more than several hundred participants; and•Phase 3. Phase 3 clinical trials are controlled clinical trials conducted in an expanded patient population at geographically dispersed clinical trialsites. They are performed after preliminary evidence suggesting effectiveness of the product candidate has been obtained and are intended to furtherevaluate dosage, clinical effectiveness and safety, to establish the overall benefit-risk relationship of the product candidate and to provide anadequate basis for regulatory approval. Phase 3 clinical trials usually involve several hundred to several thousand participants. In most cases, theFDA requires two adequate and well controlled Phase 3 clinical trials to demonstrate the efficacy of the product candidate, although a single Phase 3clinical trial with other confirmatory evidence may be sufficient in certain instances.The decision to suspend or terminate development of a product candidate may be made by either a health authority body, such as the FDA, by anIRB, or by a company for various reasons and during any phase of clinical trials. The FDA may order the temporary or permanent discontinuation of a clinicaltrial at any time or impose other sanctions if it believes that the clinical trial either is not being conducted in accordance with FDA requirements or presentsan unacceptable risk to the clinical trial patients. In some cases, clinical trials are overseen by a DSMB, which is an independent group of qualified expertsorganized by the trial sponsor to evaluate at designated points in time whether or not a trial may move forward and/or should be modified. These decisionsare based on unblinded access to data from the ongoing trial and generally involve determinations regarding the benefit-risk ratio for study patients and thescientific integrity and validity of the clinical trial.In addition, there are requirements for the registration of certain clinical trials of product candidates on public registries, such as ClinicalTrials.gov,and the submission of certain information pertaining to these trials, including clinical trial results, after trial completion.Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, a sponsor submits extensiveinformation about the product candidate to the FDA in the form of a BLA to request marketing approval for the product candidate in specified indications.Biologics License Applications36Table of ContentsIn order to obtain approval to market a biologic in the United States, a marketing application must be submitted to the FDA that provides dataestablishing the safety and effectiveness of the product candidate for the proposed indication. The application includes all relevant data available frompertinent pre-clinical studies and clinical trials, including negative or ambiguous results as well as positive findings, together with detailed informationrelating to the product’s chemistry, manufacturing, controls and proposed labeling, among other things. Data can come from company-sponsored clinicaltrials intended to test the safety and effectiveness of a product candidate, or from a number of alternative sources, including studies initiated by investigators.To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and effectiveness of the productcandidate to the satisfaction of the FDA. For example, in November 2016, the FDA issued a draft guidance document on developing new drugs and biologicsfor treating BCG-unresponsive NMIBC, and finalized this guidance in February 2018. Our BLA for Vicinium for the treatment of high-risk NMIBC may haveto meet the expectations set forth in this guidance document to obtain approval.Under the Prescription Drug User Fee Act, or PDUFA, as amended, the fees payable to the FDA for reviewing an original BLA, as well as annualprogram fees for approved products, can be substantial, subject to certain limited deferrals, waivers and reductions that may be available. The FDA has 60days from receipt of a BLA to determine whether the application will be accepted for filing based on the agency’s threshold determination that it issufficiently complete to permit substantive review. The FDA may refuse to accept for filing any BLA that it deems incomplete or not properly reviewable atthe time of submission, in which case the BLA will have to be updated and resubmitted. The FDA’s PDUFA review goal is to review 90% of priority BLAapplications within six months of filing and 90% of standard applications within 10 months of filing, but the FDA can and frequently does extend this reviewtimeline to consider certain later-submitted information or information intended to clarify or supplement information provided in the initial submission. TheFDA may not complete its review or approve a BLA within these established goal review times. The FDA reviews the BLA to determine, among other things,whether the proposed product is safe, pure, and potent for its intended use, and whether the product is being manufactured in compliance with cGMP. TheFDA may also refer applications for novel product candidates which present difficult questions of safety or efficacy to an advisory committee, typically apanel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and underwhat conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when makingdecisions.Before approving a BLA, the FDA will inspect the facilities at which the product candidate is manufactured or the facilities that are significantlyinvolved in the product development and distribution process, and will not approve the product candidate unless cGMP compliance is satisfactory.Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Under the Pediatric ResearchEquity Act, certain BLAs must include an assessment, generally based on clinical trial data, of the safety and effectiveness of the biological product inrelevant pediatric populations. The FDA may waive or defer the requirement for a pediatric assessment, either at a company’s request or by its own initiative,including waivers for certain products not likely to be used in a substantial number of pediatric patients. Products with orphan drug designation are exemptfrom these requirements for orphan-designated indications with no formal waiver process required.After the FDA evaluates the BLA and the manufacturing facilities, it issues either an approval letter or a complete response letter. A completeresponse letter generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA toreconsider the application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the BLA, the FDA may issue anapproval letter. The FDA’s PDUFA review goal to review such resubmissions is two or six months depending on the type of information included.Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatorycriteria for approval and deny approval of a resubmitted BLA. FDA approval of any application may include many delays or never be granted. An approvalletter authorizes commercial marketing of the product candidate with specific prescribing information for specific indications. As a condition of BLAapproval, the FDA may require a risk evaluation and mitigation strategy, or REMS, to help ensure that the benefits of the product outweigh the potentialrisks. REMS can include Medication Guides, communication plans for healthcare professionals, and also may include elements to assure safe use, or ETASU.ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, specialmonitoring, and the use of patient registries. The requirement for a REMS can materially affect the potential market and profitability of the biologic.Moreover, product approval may require substantial post-approval testing and surveillance to monitor the biologic’s safety, purity, or potency, which can becostly.Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes orfacilities, require submission and FDA approval of a new BLA or a supplemental BLA before the change can be implemented. A supplemental BLA for a newindication typically requires clinical data similar to that in the original application, and the FDA generally uses the same procedures and actions in reviewinga supplemental BLA as it does in reviewing a new BLA.37Table of ContentsProduct approvals may be withdrawn if compliance with regulatory standards is not maintained or if safety or manufacturing problems occurfollowing initial marketing. For example, quality control and manufacturing procedures must conform, on an ongoing basis, to cGMP requirements, and theFDA periodically inspects manufacturing facilities to assess compliance with cGMP. Accordingly, manufacturers must continue to spend time, money andeffort to maintain cGMP compliance. In addition, new or modified government requirements, including from new legislation, may be established that coulddelay or prevent regulatory approval of our product candidates under development or affect our ability to maintain product approvals we have obtained.FDA regulation of companion diagnosticsIf safe and effective use of a product candidate depends on identifying appropriate patients through an in vitro diagnostic test, then the FDAgenerally will require approval of a diagnostic test, known as an in vitro companion diagnostic device, or companion diagnostic, at the same time that theFDA approves the product candidate. The FDA issued an August 2014 guidance document addressing companion diagnostics. The FDA has requiredsponsors using companion diagnostics intended to select the patients who will respond to cancer treatment to obtain a pre-market approval, or PMA, for thosediagnostics. The review of these companion diagnostics in conjunction with the review of a cancer therapeutic involves coordination of review by the FDA’sCenter for Biologics Evaluation and Research and by the FDA’s Center for Devices and Radiological Health. During a Type C meeting with FDA in 2007, theFDA noted that approval of a companion diagnostic for EpCAM expression would need to coincide with Vicinium's approval for the treatment of SCCHN.We intend to clarify whether the FDA still believes that a companion diagnostic is necessary for approval of Vicinium in this indication.PMA applications involve a rigorous premarket development program during which the applicant must generate and provide the FDA withextensive data, including from pre-clinical and clinical studies, supporting the device’s safety and effectiveness and information about the device and itscomponents regarding, among other things, device design, manufacturing and labeling. PMA applications are subject to an application fee. For a diagnosticdevice, the applicant must demonstrate that the diagnostic produces reproducible results when the same sample is tested multiple times by multiple users atmultiple laboratories. As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality SystemRegulation, or QSR, which imposes design, testing, control, documentation and other quality assurance requirements.PMA approval is not guaranteed, and the FDA may ultimately respond to a PMA submission with a denial of approval or a “not approvable” letterbased on deficiencies in the application and require additional clinical trial or other data that may be expensive and time-consuming to generate and that cansubstantially delay approval. If the FDA’s evaluation of the PMA application is favorable, the FDA may issue an approvable letter requiring the applicant’sagreement to specific conditions, such as changes in labeling, or specific additional information, such as submission of final labeling, in order to secure finalapproval of the PMA. If the FDA concludes that the applicable criteria have been met, the FDA will issue an approval letter for the approved indications,which may be more limited than those originally sought by the applicant. The PMA can include post-approval conditions that the FDA believes necessary toensure the safety and effectiveness of the device, including, among other things, restrictions on labeling, promotion, sale and distribution. Medical devicesremain subject to extensive regulatory requirements after being approved or cleared, including under the QSR.Biosimilars and market exclusivityUnder the Biologics Price Competition and Innovation Act of 2009, or BPCIA, the FDA can approve products that are biosimilar to (but not genericcopies of) innovative biologics on the basis of less extensive data than is required by a full BLA. To be biosimilar, a biological product can have noclinically meaningful differences in safety or efficacy from the reference product. An interchangeable biosimilar product must meet additional standards forinterchangeability and, if approved, may be substituted for the reference product. At this juncture, it is unclear whether any product deemed‘‘interchangeable’’ by the FDA, in fact, will be readily substituted by pharmacies, which are governed by state pharmacy law.After an innovator has marketed its product for four years, a manufacturer may file an application for approval of a ‘‘biosimilar’’ version of theinnovator product. However, although an application for approval of a biosimilar may be filed four years after approval of the innovator product, qualifiedinnovative biological products receive 12 years of regulatory exclusivity, meaning that the FDA may not approve a biosimilar version until 12 years after theinnovative biological product was first approved by the FDA under the PHSA. The BPCIA also provides a mechanism for innovators to enforce the patentsthat protect innovative biological products and for biosimilar applicants to challenge the patents. Such patent litigation may begin as early as four years afterthe innovative biological product is first approved by the FDA. Although the patents for the reference biologic may be challenged by the biosimilarapplicant during that time period pursuant to the BPCIA statutory patent challenge framework, no biosimilar or interchangeable product will be licensed bythe FDA until the end of the exclusivity38Table of Contentsperiod. The first biologic product candidate submitted under the abbreviated approval pathway that is determined to be interchangeable with the referenceproduct has exclusivity against any other determinations of interchangeability to the reference product for the lesser of (i) one year after first commercialmarketing of the interchangeable biosimilar product, (ii) 18 months after approval of the interchangeable biosimilar product if there is no legal challenge,(iii) 18 months after the resolution in the interchangeable biosimilar product applicant’s favor of a lawsuit challenging the reference product’s patents, and(iv) 42 months after approval of the interchangeable biosimilar product if a lawsuit is ongoing within the 42-month period.The objectives of the BPCIA are conceptually similar to those of the Hatch-Waxman Act, which established abbreviated pathways for the approvalof generic drugs. The FDA has published several guidance documents providing direction on developing and obtaining approval of biosimilar productcandidates. The guidance documents to date explain, among other things, that the FDA will approve a biosimilar product if there are no clinically meaningfuldifferences between the biological product and the reference product in terms of safety, purity and potency. A determination of biosimilarity may be basedupon: (1) analytical studies showing that the biological product is highly similar to, with no clinically meaningful differences from, the reference product, (2)animal studies, including toxicity assessments, and/or (3) a clinical trial or trials (including assessment of immunogenicity and PKs or pharmacodynamics)that are sufficient to demonstrate safety, purity and potency. The FDA recommends that sponsors use a stepwise approach to developing the data andinformation needed to support biosimiliarity. At each step, the sponsor should evaluate the extent of residual uncertainty of biosimilarity that remains andincorporate the FDA’s advice for additional studies to address remaining uncertainty. To meet the higher standard for interchangeability the sponsor mustdemonstrate, in addition to biosimilarity, that the proposed biological product can be expected to produce the same clinical result and, if administered morethan once to any given patient, the safety risk and potential for diminished efficacy associated with switching between the proposed biological product andthe reference product is not greater than continuing to use the reference product. A biological product that is determined to be interchangeable may besubstituted for the reference product without the intervention of the prescribing healthcare provider. In March 2015, the FDA approved the first biosimilarproduct under the BPCIA, and it has approved other biosimilar products since then. If any of our product candidates is approved by the FDA, the approval ofa biologic product biosimilar to one of our products could have a material impact on our business. In particular, a biosimilar could be significantly less costlyto bring to market and priced significantly lower than our products, if approved by the FDA.The ‘‘Purple Book,’’ first published by the FDA in September 2014, lists biological products, including any biosimilar and interchangeablebiological products licensed by the FDA under the PHSA. The lists include the date a biological product was licensed under Section 351(a) of the PHSA andwhether the FDA evaluated the biological product for reference product exclusivity under Section 351(k)(7) of the PHSA. The Purple Book will also enable auser to see whether a biological product licensed under Section 351(k) of the PHSA has been determined by the FDA to be biosimilar to or interchangeablewith a reference biological product (an already-licensed FDA biological product). Biosimilar and interchangeable biological products licensed under Section351(k) of the PHSA will be listed under the reference product to which biosimilarity or interchangeability was demonstrated.Advertising and promotionThe FDA and other federal regulatory agencies closely regulate the marketing and promotion of biologics through standards and regulations for,among other things, direct-to-consumer advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities,and promotional activities involving the internet. A biologic cannot be commercially promoted before it is approved. After approval, promotion of a biologiccan include only those claims relating to safety and effectiveness that are consistent with the labeling approved by the FDA.Healthcare providers are permitted, however, to prescribe products for unapproved uses (also known as ‘‘off-label’’ uses) – that is, uses not approvedby the FDA and therefore not described in the product’s labeling – because the FDA does not regulate the practice of medicine. However, FDA restrictsmanufacturers’ communications regarding unapproved uses. Broadly speaking, a manufacturer may not promote a product for an unapproved use, but mayengage in non-promotional, balanced communication regarding unapproved uses under specified conditions. Failure to comply with applicable FDArequirements and restrictions in this area may subject a company to adverse publicity and enforcement action by the FDA, the Department of Justice, or theDOJ, or the Office of Inspector General of the Department of Health and Human Services, or HHS, as well as state authorities. Such enforcement action couldsubject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materiallyrestrict the manner in which a company promotes or distributes products.Post-approval regulation39Table of ContentsAfter regulatory approval of a product is obtained, a company is required to comply with a number of post-approval requirements. For example, as acondition of BLA approval, the FDA may require post-marketing testing, including Phase 4 clinical trials, and surveillance to further assess and monitor theproduct’s safety and effectiveness after commercialization. Regulatory approval of oncology products often requires that patients in clinical trials befollowed for long periods to determine the overall survival benefit of the product. In addition, as a holder of an approved BLA, a company would be requiredto report adverse reactions and production problems to the FDA, to provide updated safety and efficacy information, and to comply with requirementsconcerning advertising and promotional labeling for any of its products.The manufacturing of our product candidates is required to comply with applicable FDA manufacturing requirements contained in the FDA’s cGMPregulations. Our product candidates were manufactured at our production plant in Winnipeg, Manitoba, Canada. In September 2017 we completed themanufacturing of all Vicinium necessary for our ongoing Phase 3 registration trial in patients with NMIBC, and for our CRADA with the NCI. In the event weobtain approval from the FDA to market any of our product candidates, we will need to outsource our commercial scale manufacturing to CMOs. Qualitycontrol and manufacturing procedures must continue to conform to cGMP after approval to assure and preserve the long term stability of the biologicalproduct. Biologic manufacturers and other entities involved in the manufacture and distribution of approved biologics are also required to register theirestablishments and list any products they make with the FDA and to comply with related requirements in certain states. The FDA and certain state agenciesperiodically inspect manufacturing facilities to assess compliance with cGMP and other laws.Discovery of problems with a product after approval may result in serious and extensive restrictions on a product or the manufacturer or holder of anapproved BLA, as well as lead to potential market disruptions. These restrictions may include suspension of product manufacturing until the FDA is assuredthat quality standards can be met, continuing oversight of manufacturing by the FDA under a ‘‘consent decree,’’ which frequently includes the imposition ofcosts and continuing inspections over a period of many years, as well as possible withdrawal of the product from the market. Other potential consequencesinclude interruption of production, issuance of warning letters or other enforcement letters, refusal to approve pending BLAs or supplements to approvedBLAs, product seizure or detention, and injunctions or imposition of civil and/or criminal penalties.In addition, changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDAapproval before being implemented. FDA regulations also require investigation, correction, and reporting of any deviations from cGMP and impose reportingand documentation requirements upon a company and any third party manufacturers that a company may decide to use. Accordingly, manufacturers mustcontinue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatorycompliance.Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of newwarnings and contraindications, and also may require the implementation of other risk management measures, such as additional post-market clinical trials toassess new safety risks or distribution-related or other restrictions under a REMS.Patent Term ExtensionDepending upon the timing, duration and specifics of the FDA approval of our product candidates, some of our U.S. patents may be eligible forlimited patent term extension. The provisions of the Hatch-Waxman Act permit a patent restoration term of up to five years as compensation for patent termlost during product development and the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patentbeyond a total of 14 years from the product’s approval date. The patent term restoration period is generally one-half the time between the effective date of anIND and the submission date of a BLA plus the time between the submission date of a BLA and the approval of that application. Only one patent applicableto an approved product is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The UnitedStates Patent and Trademark Office, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. In thefuture, we may apply for restoration of patent term for one of our currently owned or licensed patents to add patent life beyond its current expiration date,depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA.Many other countries also provide for patent term extensions or similar extensions of patent protection for biologic products. For example, in Japan,it may be possible to extend the patent term for up to five years and in Europe, it may be possible to obtain a supplementary patent certificate that wouldeffectively extend patent protection for up to five years.The Foreign Corrupt Practices Act40Table of ContentsThe Foreign Corrupt Practices Act, or FCPA, prohibits any U.S. individual or business from paying, offering, or authorizing payment or offering ofanything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreignentity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in theUnited States to comply with accounting provisions requiring such companies to maintain books and records that accurately and fairly reflect all transactionsof the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for internationaloperations.Canadian Government RegulationIn Canada, Health Canada is responsible for the regulation of pharmaceuticals under the authority of the Food and Drugs Act and the Food and DrugRegulations. Any compound that fits under the definition of ‘‘drug’’ as defined in the Food and Drugs Act must undergo a series of trials (for example, Phase1, 2 and 3, similar to the United States) to demonstrate it is both safe and effective before it can be marketed in Canada. Approval is based on a risk-benefitassessment, in which the therapeutic benefits are weighed against the risks associated with taking the drug.All clinical drug trials taking place in Canada are regulated through the Food and Drug Regulations, which is supplemented by the Good ClinicalPractice: Consolidated Guidelines. A failure to comply with any requirements during product development, approval, or post-approval periods may lead toadministrative or judicial sanctions. These sanctions could include fines, suspension or cancellation of regulatory approvals, closure of a clinical trial,product recalls, seizure of products, operating restrictions, injunctions, criminal penalties, and criminal prosecution. Our product candidates are biologics andtherefore come under the purview of the Biologics and Genetic Therapies Directorate of Health Canada. To receive approval from Health Canada, biologics,like all drugs, must be shown to be safe and effective. In addition, biologics must be shown to be of suitable quality in terms of both chemistry andmanufacturing. This latter requirement increases the regulatory burden, requiring additional submissions and mandatory inspections with respect to themethod of manufacture, similar to that in the United States. Health Canada also has rules relating to the approval of subsequent entry biologics in Canada,following the expiry of an innovator biologic’s data exclusivity and/or patent protection.The Canadian drug approval process requires submission and approval of a CTA as well as approval by a Research Ethics Board before each phaseof human clinical trials is commenced. Canadian clinical trial development is similar to the clinical trial phases of the United States.ExclusivityUnder the Food and Drug Regulations there are data exclusivity provisions for ‘‘innovative drugs’’ that have not been previously approved in adrug by the relevant Minister and that is not a variation of a previously approved medicinal ingredient such as a salt, ester, enantiomer, or polymorph. Theterm of data exclusivity is presently eight years from the date of first market approval which can be extended to an additional six months for pediatricindications if an innovator includes, in its new drug submission, or any supplement to that new drug submission filed within the first five years of the eight-year data protection period, results of clinical trials which were designed and conducted with the purpose of increasing knowledge about the use of the drugin pediatric populations and which will lead to a health benefit for children.Also, provided certain requirements are met, the newly implemented Certificate of Supplementary Protection regime in Canada (intended to partlycompensate for time spent in research and obtaining marketing authorization) can provide for up to two years of additional protection from the expiry of apatent, for drugs containing a new medicinal ingredient, or a combination thereof, protected by an eligible patent.In addition, Canada, similar to the United States, has patent/regulatory linkage provisions. The Patented Medicines (Notice of Compliance)Regulations enable a patent with claims to the medicinal ingredient, formulation, dosage form or use to be listed on the Patent Register. A second person whofiles a drug submission that directly or indirectly compares itself to a drug wherein there is a patent on the Patent Register will not obtain marketauthorization for their product until the patent term has expired, it is determined that they will not be infringing the patent, the patent is held invalid or theinclusion of the patent on the Patent Register is found to have been made through certain false statements. Although a stay pending the outcomes of anyassociated proceedings (up to two years) may be obtained, it can be costly, and success is not guaranteed. If a company is not successful in any suchproceeding, they may be liable for damages and also may result in a competitor’s product receiving market authorization.Advertising, Promotion and Compliance41Table of ContentsAdvertising and promotion of health products, particular prescription drugs/biologics is regulated primarily by Health Canada pursuant to the Foodand Drugs Act and Regulations, by standards set by the Pharmaceutical Advertising Advisory Board, Advertising Standards Canada and industryassociations, such as Innovative Medicines Canada, the national association representing Canadians who work for Canadian research-based pharmaceuticalcompanies, and their Code of Ethical Practices. In addition, Canada has the Competition Act and the Corruption of Foreign Public Officials Act. All of thesedefine how drugs can be advertised and what are or are not permitted activities and interactions with public officials, healthcare professionals, the public andother stakeholders. For example, in Canada direct to consumer advertising of prescription drugs is generally prohibited. Failure to comply can result insanctions, fines, suspension or cancellation of regulatory approvals, closure of a clinical trial, product recalls, seizure of products, operating restrictions,injunctions, criminal penalties, and criminal prosecution.European Union and other international government regulationIn addition to regulations in the United States, we will be subject to a variety of regulations in other jurisdictions governing, among other things,clinical trials and any commercial sales and distribution of our product candidates. Whether or not we obtain FDA approval for a product candidate, we mustobtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of a product in thosecountries. Some countries outside of the United States have a similar process that requires the submission of a CTA much like the IND prior to thecommencement of human clinical trials. In the E.U., for example, a CTA must be submitted to the competent authorities of the E.U. Member States where theclinical trial is conducted and to an independent ethics committee, much like the FDA and IRB, respectively. Once the CTA is approved in accordance with acountry’s requirements, clinical trial development may proceed.Marketing authorization application for biologic medicinal products in the European Union and in other foreign countriesTo obtain regulatory approval to commercialize a new drug under E.U. regulatory systems, we must submit a marketing authorization application.In the E.U., a marketing authorization for a medicinal product can be obtained through a centralized, mutual recognition, decentralized procedure, ornational procedure (single country). The centralized procedure is mandatory for certain medicinal products, including orphan medicinal products andbiologic products and optional for certain other products, including medicinal products that are a significant therapeutic, scientific or technical innovation,or whose authorization would be in the interest of public or animal health.In accordance with the centralized procedure, the applicant can submit a single application for marketing authorization to the EMA which willprovide a positive opinion regarding the application if it meets certain quality, safety, and efficacy requirements. Based on the opinion of the EMA, theEuropean Commission takes a final decision to grant a centralised marketing authorization which permits the marketing of a product in all 28 E.U. MemberStates and three of the four European Free Trade Association States, Iceland, Liechtenstein and Norway. Under the centralized procedure in the E.U., themaximum timeframe for the evaluation of a marketing authorization application is 210 days (excluding clock stops, when additional written or oralinformation is to be provided by the applicant in response to questions asked by the EMA Committee for Medicinal Products for Human Use, or CHMP).For other countries outside of the E.U., such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct ofclinical trials, product licensing, pricing and reimbursement vary from country to country. Internationally, clinical trials are generally required to beconducted in accordance with GCPs, applicable regulatory requirements of each jurisdiction and the medical ethics principles that have their origin in theDeclaration of Helsinki. If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension orwithdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.Advertising, Promotion and ComplianceIn the E.U., the advertising and promotion of our products will also be subject to E.U. laws and E.U. Member States’ national laws governingpromotion of medicinal products, interactions with physicians, misleading and comparative advertising and unfair commercial practices. Other E.U. MemberState national legislation may also apply to the advertising and promotion of medicinal products. These laws require that promotional materials andadvertising in relation to medicinal products comply with the product’s Summary of Product Characteristics, or SmPC, as approved by the competentauthorities. The SmPC is the document that provides information to physicians concerning the safe and effective use of the medicinal product. The SmPCforms an intrinsic and integral part of the marketing authorization granted for the medicinal product. Promotion of a medicinal42Table of Contentsproduct that does not comply with the SmPC is considered to constitute off-label promotion and is prohibited in the E.U. The applicable laws at the E.U.level and in the individual E.U. Member States also prohibit the direct-to-consumer advertising of prescription-only medicinal products. Violations of therules governing the promotion of medicinal products in the E.U. could be penalized by administrative measures, fines and imprisonment.During all phases of development (pre- and post-marketing), failure to comply with applicable regulatory requirements may result in administrativeor judicial sanctions. These penalties imposed by the European Commission, the competent authorities of the E.U. Member States or comparable foreignregulatory authorities could include the imposition of a clinical hold on trials, refusal to approve pending applications, withdrawal of an approval, warningletters, product recalls, product seizures, total or partial suspension of production or distribution, product detention or refusal to permit the import or export ofproducts, injunctions, fines, civil penalties or criminal prosecution. Any agency or judicial enforcement action could have a material adverse effect on us.Regulation of in vitro diagnostic medical devices in the European UnionIn the E.U., companion diagnostics are regulated as in vitro diagnostic medical devices, or IVDs. Manufacturers of IVDs are required to comply withthe Essential Requirements laid down in Annex I to the Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitrodiagnostic medical devices, or the IVD Directive. Compliance with these requirements entitles manufacturers to affix the CE mark to their IVDs, withoutwhich they cannot be commercialized in the E.U. To demonstrate compliance with the Essential Requirements laid down in Annex I to the IVD Directive andobtain the right to affix the CE mark to the IVDs, manufacturers must undergo a conformity assessment procedure, which varies according to the type of IVDs.The IVD Directive groups IVDs into four categories based on the risks associated with relative dangers to public health and / or patient treatment by an IVDfailing to perform as intended:•General IVDs;•IVDs for self-testing;•IVDs falling within the scope of Annex II, List A:•reagents and reagent products, including related calibrators and control materials, for determining the following blood groups: ABOsystem, rhesus (C, c, D, E, e), or anti-Kell; and•reagents and reagent products, including related calibrators and control materials, for the detection, confirmation and quantification inhuman specimens of markers of human immunodeficiency virus, or HIV, infection (HIV 1 and 2), human T-lymphotropic virus I and II, andhepatitis B, C and D.•IVDs falling within the scope of Annex II, List B:•reagents and reagent products, including related calibrators and control materials, for determining the following blood groups: anti-Duffyand anti-Kidd;•reagents and reagent products, including related calibrators and control materials, for determining irregular anti-erythrocyte antibodies;•reagents and reagent products, including related calibrators and control materials, for the detection and quantification in human samples ofthe following congenital infections: rubella, toxoplasmosis;•reagents and reagent products, including related calibrators and control materials, for diagnosing the following hereditary disease:phenylketonuria;•reagents and reagent products, including related calibrators and control materials, for determining the following human infections:cytomegalovirus, chlamydia;•reagents and reagent products, including related calibrators and control materials, for determining the following human leukocyte antigentissue groups: DR, A, B;•reagents and reagent products, including related calibrators and control materials, for determining the following tumoral marker: prostate-specific antigen;•reagents and reagent products, including related calibrators, control materials and software, designed specifically for evaluating the risk oftrisomy 21; and•the following device for self-diagnosis, including its related calibrators and control materials: device for the measurement of blood sugar.43Table of ContentsFollowing determination of the appropriate category for an IVD, manufacturers are required to follow the related conformity assessment procedureslaid down in Article 9 of the IVD Directive.For general IVDs, a self-assessment process in accordance with Annex III of the IVD Directive and a related Declaration of Conformity by themanufacturer prior to affixing the CE mark is sufficient. In the Declaration of Conformity, the manufacturer certifies that its product complies with theEssential Requirements provided for in Annex I to the IVD Directive.For IVD for self-testing and those falling within List A or B of Annex II to the IVD, a notified body must undertake an assessment of the conformityof the manufacturer and/or the device with the applicable provisions of the IVD Directive.The notified body would commonly audit and examine a product Technical File and the quality management system for the manufacture, design,and final inspection of a medical device before issuing a CE Certificate of Conformity demonstrating compliance with the requirements of the IVD Directive.Following the issuance of a CE Certificate of Conformity, manufacturers can draw up the Declaration of Conformity and affix the CE mark to the productscovered by the CE Certificate of Conformity and the Declaration of Conformity.In the European Union, companion diagnostics for EpCAM expression are regulated as general IVDs. The involvement of a notified body during theconformity assessment procedure is not, therefore, currently required. This situation will, however, change with the new Regulation on In Vitro DiagnosticMedical Devices, or IVDR, which will be applicable from May 26, 2022. The Regulation, which will replace the IVD Directive from May 2022, willsubstantially impact IVD manufacturers. In accordance with the new IVDR, companion diagnostics will be regulated as Class C IVDs and a notified body willbe required to participate in the related conformity assessment procedure.Orphan Drug DesignationThe FDA may grant Orphan Drug Designation to biologics intended to treat a rare disease or condition that affects fewer than 200,000 individuals inthe United States, or, a disease or condition that affects more than 200,000 individuals in the United States but there is no reasonable expectation that thecost of developing and making the drug would be recovered from sales in the United States. In the E.U., the EMA’s Committee for Orphan MedicinalProducts grants Orphan Drug Designation to promote the development of products that are intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions affecting not more than five in 10,000 persons in the E.U. community. Additionally, designation is grantedfor products intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition and when,without incentives, it is unlikely that sales of the drug in the E.U. would be sufficient to justify the necessary investment in developing the biologic.In the United States, orphan drug designation entitles a party to financial incentives, such as opportunities for grant funding towards clinical trialcosts, tax credits for certain research and user fee waivers under certain circumstances. In addition, if a product receives the first FDA approval for theindication for which it has orphan designation, the product is entitled to seven years of market exclusivity, which means the FDA may not approve any otherapplication for the same biologic for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiorityover the product with orphan exclusivity. The FDA can revoke a product’s orphan drug exclusivity under certain circumstances, including when the productsponsor is unable to assure the availability of sufficient quantities of the product to meet patient needs. Orphan drug exclusivity does not prevent the FDAfrom approving a different drug for the same disease or condition, or the same biologic for a different disease or condition.In the E.U., medicinal products: (a) that are used to treat or prevent life-threatening or chronically debilitating conditions that affect no more thanfive in 10,000 people in the E.U.; or (b) that are used to treat or prevent life-threatening or chronically debilitating conditions and that, for economic reasons,would be unlikely to be developed without incentives; and (c) where no satisfactory method of diagnosis, prevention or treatment of the condition concernedexists, or, if such a method exists, the medicinal product would be of significant benefit to those affected by the condition, may be granted an orphandesignation in the E.U. The application for orphan designation must be submitted to the EMA and approved by the European Commission before anapplication is made for marketing authorization for the product. Once authorized, Orphan medicinal product designation also entitles a party to financialincentives such as reduction of fees or fee waivers. Moreover, ten years of market exclusivity is granted following biologic approval. During this ten-yearperiod, with a limited number of exceptions, neither the competent authorities of the E.U. Member States, the EMA, or the European Commission arepermitted to accept applications or grant marketing authorization for other similar medicinal products with the same therapeutic indication. However,marketing authorization may be granted to a similar medicinal product with the same orphan indication during the ten-year period with the consent of themarketing authorization holder for the original orphan medicinal product or if the manufacturer of the original orphan medicinal product is unable to supplysufficient quantities. Marketing authorization may44Table of Contentsalso be granted to a similar medicinal product with the same orphan indication if this latter product is demonstrated to be safer, more effective or otherwiseclinically superior to the original orphan medicinal product. This period of market exclusivity may be reduced to six years, at the end of the fifth year, if theorphan designation criteria are no longer met, including where it can be demonstrated on the basis of available evidence that the product is sufficientlyprofitable not to justify maintenance of market exclusivity. Additionally, marketing authorization may be granted to a similar product during the ten-yearperiod of market exclusivity for the same therapeutic indication at any time if:•The second applicant can establish in its application that its product, although similar to the orphan medicinal product already authorized, is safer,more effective or otherwise clinically superior;•The holder of the marketing authorization for the original orphan medicinal product consents to a second orphan medicinal product application; or•The holder of the marketing authorization for the original orphan medicinal product cannot supply enough orphan medicinal product.There is currently no orphan drug designation in Canada.Orphan drug designation must be requested before submission of an application for marketing approval or marketing authorization. Orphan drugdesignation does not convey any advantage in, or shorten the duration of the regulatory review and approval process.Vicinium has received Orphan Drug Designation from the FDA and the EMA for the treatment of SCCHN.Expedited Programs in the United States and Other JurisdictionsIn the United States, a product may be granted fast track designation if it is intended for the treatment of a serious or life-threatening condition anddemonstrates the potential to address unmet medical needs for such condition. With fast-track designation, the sponsor may be eligible for more frequentopportunities to obtain the FDA’s feedback, and the FDA may initiate review of sections of a BLA before the application is complete. This ‘‘rolling review’’is available if the applicant provides and the FDA approves a schedule for the remaining information. Even if a product receives fast-track designation, thedesignation can be rescinded and provides no assurance that a product will be reviewed or approved more expeditiously than would otherwise have been thecase, or that the product will be approved at all.FDA may designate a product candidate as a breakthrough therapy if it finds that the product candidate is intended, alone or in combination withone or more other product candidates or approved products, to treat a serious or life-threatening disease or condition, and preliminary clinical evidenceindicates that the product candidate may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Forproduct candidates designated as breakthrough therapies, more frequent interaction and communication between the FDA and the sponsor can help toidentify the most efficient path for clinical development. Product candidates designated as breakthrough therapies by the FDA may also be eligible forpriority review. We may apply for breakthrough therapy designation for some of our product candidates. However, even if we believe one of our productcandidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and determine not to make such designation. In any event, thereceipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to productcandidates considered for approval under conventional FDA procedures and, in any event, does not assure ultimate approval by the FDA. In addition, even ifone or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that the product candidates no longer meet the conditionsfor designation.Accelerated approval under FDA regulations allows a product designed to treat a serious or life-threatening disease or condition that provides ameaningful therapeutic advantage over available therapies to be approved on the basis of either an intermediate clinical endpoint or a surrogate endpointthat is reasonably likely to predict clinical benefit. Approvals of this kind typically include requirements for confirmatory clinical trials to be conducted withdue diligence to validate the surrogate endpoint or otherwise confirm clinical benefit, and for all promotional materials to be submitted to the FDA for reviewprior to dissemination.FDA may grant priority review designation to a product candidate, which sets the target date for FDA action on the application at six months fromFDA filing, or eight months from the sponsor’s submission. Priority review may be granted where a product is intended to treat a serious or life-threateningdisease or condition and, if approved, has the potential to provide a safe and effective therapy where no satisfactory alternative therapy exists or a significantimprovement in safety or efficacy compared to available therapy. If criteria are not met for priority review, the standard FDA review period is ten months45Table of Contentsfrom FDA filing, or 12 months from sponsor submission. Priority review designation does not change the scientific/medical standard for approval or thequality of evidence necessary to support approval.In Canada, Health Canada has a Priority Review Process, allowing for shortened review targets of eligible drug submissions. Eligibility for PriorityReview is similar to that of the United States. The drug submission must be for a serious, life-threatening or severely debilitating disease or condition forwhich there is substantial evidence of clinical effectiveness that the drug provides (a) effective treatment, prevention or diagnosis of a disease or condition forwhich no drug is presently marketed in Canada; or (b) a significant increase in efficacy and/or significant decrease in risk such that the overall benefit/riskprofile is improved over existing therapies, preventatives or diagnostic agents for a disease or condition that is not adequately managed by a drug marketedin Canada. Priority Review does not change the quality, safety, or efficacy requirements of the submission; it just shortens Health Canada’s target reviewtimeline from 300 days down to 180 days.Under the Centralized Procedure in the E.U., the maximum timeframe for the evaluation of a marketing authorization application is 210 days(excluding ‘‘clock stops,’’ when additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP.Accelerated evaluation might be granted by CHMP in exceptional cases, when a medicinal product is expected to be of a major public health interest,defined by three cumulative criteria: (1) the seriousness of the disease (for example, heavy disabling or life-threatening diseases) to be treated, (2) the absenceor insufficiency of an appropriate alternative therapeutic approach, and (3) anticipation of high therapeutic benefit. In this circumstance, EMA ensures thatthe opinion of CHMP is given within 150 days.Vicinium has received Fast Track designation from the FDA for the treatment of SCCHN and NMIBC.Healthcare ReformIn the United States and some foreign jurisdictions, there have been, and continue to be, a number of legislative and regulatory changes andproposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of our product candidates, restrict orregulate post-approval activities and affect our ability, or the ability of any collaborators, to profitably sell any products for which we, or they, obtainmarketing approval. We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorouscoverage criteria and in additional downward pressure on the price that we, or any collaborators, may receive for any approved products.In the United States, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, as amended by the Health Care and EducationReconciliation Act of 2010, or Medicare Modernization Act, established the Medicare Part D program and generally authorized prescription drug plansponsors to impose limits on the number of covered drugs under their plans in a therapeutic class. The Medicare Modernization Act, including its costreduction initiatives, could decrease the coverage and reimbursement rate that we may receive for any of our product candidates, if approved. The Centers forMedicare & Medicaid Services, or CMS, the agency that administers the Medicare program, also may revise reimbursement and implement coveragerestrictions. Cost reduction initiatives and changes in coverage could decrease utilization of and reimbursement for any approved products, which wouldthen affect the price we can receive. Private payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates.Therefore, any reduction in reimbursement from federal legislation or regulation may lead to similar reductions in private payor reimbursement.In addition, in March 2010, President Obama signed one of the most significant healthcare reform measures in decades. The Affordable Care Act, asamended by the Health Care and Education Reconciliation Act, collectively the Affordable Care Act, substantially changed the way healthcare is financedby both governmental and private insurers and significantly impacts the pharmaceutical industry. The Affordable Care Act has impacted existing governmenthealthcare programs and has resulted in the development of new programs. For example, the Affordable Care Act provides for Medicare payment forperformance initiatives and improvements to the physician quality reporting system and feedback program.Among the Affordable Care Act’s provisions of importance to the pharmaceutical industry are the following:•an annual, non-deductible fee on any entity that manufactures or imports specified branded prescription products and biological products;•an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% for innovator drugs and13% for non-innovator drugs of the average manufacturer price;•a new methodology by which average manufacturer price is calculated and reported by manufacturers for products that are inhaled, infused, instilled,implanted or injected and not generally dispensed through retail community pharmacies;46Table of Contents•expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal Anti-Kickback Statute, new governmentinvestigative powers, and enhanced penalties for noncompliance;•a new partial prescription drug benefit for Medicare recipients, or Medicare Part D, coverage gap discount program, in which manufacturers mustagree to offer 50% point-of-sale discounts off negotiated prices of applicable brand products to eligible beneficiaries during their coverage gapperiod, as a condition for the manufacturers’ outpatient products to be covered under Medicare Part D;•extension of manufacturers’ Medicaid rebate liability from fee-for-service Medicaid utilization to include the utilization of Medicaid managed careorganizations as well;•expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals,thereby potentially increasing manufacturers’ Medicaid rebate liability;•expansion of the entities eligible for discounts under the Public Health Service 340B drug pricing program;•new requirements to report to CMS annually specifying financial arrangements with physicians and teaching hospitals, as defined in the AffordableCare Act and its implementing regulations, including reporting any ‘‘payments or other transfers of value’’ made or distributed to prescribers,teaching hospitals, and other healthcare providers and reporting any ownership and investment interests held by physicians and other healthcareproviders and their immediate family members and applicable group purchasing organizations during the preceding calendar year;•a new requirement to annually report product samples that manufacturers and distributors provide to physicians;•a mandatory non-deductible payment for employers with 50 or more full-time employees (or equivalents) who fail to provide certain minimumhealth insurance coverage for such employees and their dependents;•establishment of the Center for Medicare and Medicaid Innovation within CMS to test innovative payments and service delivery models; and•a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, alongwith funding for such researchIn addition, other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. For example, beginning April 1,2013, Medicare payments for all items and services, including prescription drugs and biologics, were reduced by 2% under the sequestration required by theBudget Control Act of 2011, as amended by the American Taxpayer Relief Act of 2012. Subsequent legislation has extended the reduction through 2027.TheAmerican Taxpayer Relief Act of 2012 also reduced Medicare payments to several categories of healthcare providers and increased the statute of limitationsperiod for the government to recover overpayments to providers from three to five years.Additional legislative changes, FDA or CMS regulation, or guidance could be adopted, which may impact the marketing approvals andreimbursement for our product candidates. For example, there have been several Congressional inquiries and proposed bills and regulatory initiativesdesigned to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, andreform government program reimbursement methodologies for drug products.Some of the provisions of the Affordable Care Act have yet to be fully implemented, and certain provisions have been subject to judicial andCongressional challenges. In addition, there have been efforts by the Trump administration to repeal or replace certain aspects of the ACA and to alter theimplementation of the ACA and related laws. For example, the Tax Cuts and Jobs Act enacted on December 22, 2017, eliminated the tax-based sharedresponsibility payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code of 1986,commonly referred to as the “individual mandate,” effective January 1, 2019. Further, the Bipartisan Budget Act of 2018 among other things, amended theMedicare statute, effective January 1, 2019, to reduce the coverage gap in most Medicare drug plans, commonly known as the “donut hole,” by raising themanufacturer discount under the Medicare Part D coverage gap discount program to 70%. Additional legislative changes, regulatory changes, and judicialchallenges related to the Affordable Care Act remain possible. It is unclear how the Affordable Care Act and its implementation, as well as efforts to repeal orreplace, or invalidate, the Affordable Care Act, or portions thereof, will affect our business. It is possible that the Affordable Care Act, as currently enacted ormay be amended in the future, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicareand other healthcare funding, more rigorous coverage criteria, and new payment methodologies and in additional downward pressure on coverage andpayment and the price that we receive for any approved product. Any reduction in reimbursement from Medicare or other government programs may result ina similar reduction in payments from private payors.47Table of ContentsCoverage, pricing and reimbursementSignificant uncertainty exists as to the coverage and reimbursement status of any products for which we obtain regulatory approval. In the UnitedStates and in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability ofreimbursement from third-party payors. Third-party payors include government health administrative authorities, managed care providers, private healthinsurers and other organizations. The process for determining whether a payor will provide coverage for a biologic may be separate from the process forsetting the price or reimbursement rate that the payor will pay for the biologic. Third-party payors may limit coverage to specific products on an approvedlist, or formulary, which might not include all of the products approved by the FDA, Health Canada or comparable foreign regulatory authorities for aparticular indication or if a product is included it may not be listed on the formulary for all the indications or it may be listed on a narrower basis than what isapproved by the FDA, Health Canada or comparable foreign regulatory authorities. Third-party payors are increasingly challenging the price and examiningthe medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. We may need to conduct expensivepharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtainFDA, Health Canada or other comparable foreign regulatory authorities’ approvals. A payor’s decision to provide coverage for a product does not imply thatan adequate reimbursement rate will be approved. Adequate third party reimbursement may not be available to enable us to maintain price levels sufficient torealize an appropriate return on our investment in product development.In 2003, the United States Congress enacted legislation providing Medicare Part D, which became effective at the beginning of 2006. Governmentpayment for some of the costs of prescription drugs may increase demand for any products for which we receive marketing approval. However, to obtainpayments under this program, we would be required to sell products to Medicare recipients through prescription drug plans operating pursuant to thislegislation. These plans will likely negotiate discounted prices for our products. Federal, state and local governments in the United States continue toconsider legislation to limit the growth of healthcare costs, including the cost of prescription drugs. Future legislation could limit payments forpharmaceuticals such as the product candidates that we are developing.Different pricing and reimbursement schemes exist in other countries. In Canada, the Patented Medicines Prices Review Board evaluates andcontrols excessive pricing of patented products. Further, there are national, provincial and territorial formularies funded by government healthcare systems, inaddition to formularies for private payors (private insurers) and hospitals or hospital groups. Listing on the formularies and price depend on evidence andsubmissions regarding the cost-benefit of the drug and comparison of the cost-effectiveness of a particular product candidate to currently available therapiesand is often subject to negotiations.In the E.U., once a marketing authorization is granted for a medicinal product the applicant is required to engage in pricing and reimbursementdiscussions and negotiate with a separate pricing authority in each of the E.U. Member States. The E.U. Member States governments influence the price ofpharmaceutical products through their pricing and reimbursement rules and control of national healthcare systems that fund a large part of the cost of thoseproducts to consumers. Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement pricehas been agreed upon. To obtain reimbursement or pricing approval, some of the E.U. Member States may require the completion of clinical trials thatcompare the cost-effectiveness of a particular product candidate to currently available therapies. Other E.U. Member States allow companies to fix their ownprices for medicinal products, but monitor and control company profits. The downward pressure on healthcare costs in general, particularly pharmaceuticals,has become more intense. As a result, increasingly high barriers are being erected to the entry of new products. Furthermore, an increasing number of E.U.Member States and other foreign countries use prices for medicinal products established in other countries as “reference prices” to help determine the price ofthe product in their own territory. Consequently, a downward trend in prices of medicinal products in some countries could contribute to similar downwardtrends elsewhere. The E.U. Member States have discretion to restrict the range of medicinal products for which their national health insurance systemsprovide reimbursement and to control the prices of medicinal products for human use. An E.U. Member State may approve a specific price for the medicinalproduct or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market. Wemay face competition for our products, if approved, from lower priced products in foreign countries that have placed price controls on pharmaceuticalproducts. In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country.The sole legal instrument at the E.U. level governing the pricing and reimbursement of medicinal products is Council Directive 89/105/EEC, or theTransparency Directive. The aim of the Transparency Directive is to ensure that pricing and reimbursement mechanisms established in the E.U. MemberStates are transparent and objective, do not hinder the free movement and trade of medicinal products in the E.U. and do not hinder, prevent or distortcompetition on the market. The Transparency Directive does not provide any guidance concerning the specific criteria on the basis of which pricing and48Table of Contentsreimbursement decisions are to be made in individual E.U. Member States. Neither does it have any direct consequence for pricing nor reimbursement levelsin individual E.U. Member States.Health Technology Assessment, or HTA, of medicinal products is becoming an increasingly common part of the pricing and reimbursementprocedures in some E.U. Member States. These E.U. Member States include the United Kingdom, France, Germany, Ireland, Italy and Sweden. The HTAprocess in European Economic Area, or EEA, countries is governed by the national laws of these countries. HTA is the procedure according to which theassessment of the public health impact, therapeutic impact and the economic and societal impact of use of a given medicinal product in the nationalhealthcare systems of the individual country is conducted. HTA generally focuses on the clinical efficacy and effectiveness, safety, cost, and cost-effectiveness of individual medicinal products as well as their potential implications for the healthcare system. Those elements of medicinal products arecompared with other treatment options available on the market.The outcome of HTA regarding specific medicinal products will often influence the pricing and reimbursement status granted to these medicinalproducts by the competent authorities of individual E.U. Member States. The extent to which pricing and reimbursement decisions are influenced by the HTAof the specific medicinal product vary between E.U. Member States.In 2011, Directive 2011/24/EU was adopted at the EU level. This Directive concerns the application of patients’ rights in cross-border healthcare.The Directive is intended to establish rules for facilitating access to safe and high-quality cross-border healthcare in the EU. Pursuant to this Directive, avoluntary network of national authorities or bodies responsible for HTA in the individual E.U. Member States was established. The purpose of the network isto facilitate and support the exchange of scientific information concerning HTAs. This may lead to harmonization of the criteria taken into account in theconduct of HTAs between E.U. Member States and in pricing and reimbursement decisions and may negatively affect price in at least some E.U. MemberStates.The marketability of any products for which we receive regulatory approval for commercial sale may suffer if the government and third party-payorsfail to provide adequate coverage and reimbursement. In addition, an increasing emphasis on managed care in the United States has increased and willcontinue to increase the pressure on pharmaceutical pricing. Coverage policies and third party reimbursement rates may change at any time.Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorablecoverage policies and reimbursement rates may be implemented in the future.American Society of Clinical Oncology, or ASCO, value assessment for cancer treatmentsOn May 31, 2016, ASCO published a framework to assess the value of cancer treatment options. The framework was developed in response toconcern that new, expensive cancer treatments may not be supported by adequate medical evidence. The purpose of the framework is to provide astandardized quantification of cancer treatments and assist oncologists and patients in deciding between new cancer treatments and the standard of care. Theframework takes into account a medication’s (i) efficacy, (ii) safety and (iii) cost, to derive an overall treatment value.This framework is described by ASCO as providing a basis for a new software tool that doctors can use to assist shared decision-making with theirpatients. While we believe that the safety and efficacy profiles of our product candidates are potentially better than that of the standard of care and, ifapproved, we intend to price our products competitively, we do not know how the data will be assessed by ASCO. It is also unknown whether use of thisapplication could adversely affect the assessment of any of our product candidates. If this framework and software were adopted and utilized by payors andphysicians, and if our product candidates were to receive low ratings, this could adversely affect the price and reimbursement of our product candidates, ifapproved, reduce prescriptions and harm our business.Other healthcare laws and compliance requirementsHealthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation andprescription of any product candidate for which we obtain marketing approval. Our arrangements with third-party payors and customers may expose us in thefuture to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements andrelationships through which we market, sell and distribute any products for which we obtain marketing approval. In addition, we may be subject totransparency laws and patient privacy regulation by U.S. federal and state governments and by governments in foreign jurisdictions in which we conduct ourbusiness. We have described below some of the key federal, state and foreign healthcare laws and regulations that may affect our ability to operate.49Table of ContentsThe federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration toinduce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any healthcare item or service reimbursable underMedicare, Medicaid or other federally financed healthcare programs. This statute has been interpreted to apply to arrangements between pharmaceuticalmanufacturers on one hand and prescribers, purchasers, and formulary managers on the other. Although there are a number of statutory exemptions andregulatory safe harbors protecting some business arrangements from prosecution, the exemptions and safe harbors are drawn narrowly and practices thatinvolve remuneration intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exemption or safeharbor. Our practices may not in all cases meet all of the criteria for safe harbor protection from federal Anti-Kickback Statute liability. Liability may beestablished under the federal Anti-Kickback Statute without proving actual knowledge of the statute or specific intent to violate it. In addition, thegovernment may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulentclaim for purposes of the civil False Claims Act (discussed below).The federal civil False Claims Act prohibits, among other things, any person from knowingly presenting, or causing to be presented, a false orfraudulent claim for payment of government funds; knowingly making, using, or causing to be made or used a false record or statement material to a false orfraudulent claim to the federal government; or knowingly concealing or knowingly and improperly avoiding, decreasing, or concealing an obligation to paymoney to the federal government. The False Claims Act also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federalgovernment alleging violations of the statute and to share in any monetary recovery. Pharmaceutical and other healthcare companies have faced enforcementactions under the federal civil False Claims Act for, among other things, allegedly providing free product to customers with the expectation that thecustomers would bill federal programs for the product and for allegedlycausing false claims to be submitted because of the companies’ marketing of theproduct for unapproved, and thus non-reimbursable, uses. In addition, a claim can be deemed to be false due to failure to comply with legal or regulatoryrequirements material to the government’s payment decision. False Claims Act liability is potentially significant in the healthcare industry because thestatute provides for treble damages and significant mandatory penalties per false claim or statement. Pharmaceutical and other healthcare companies also aresubject to other federal false claims laws, including, among others, federal criminal healthcare fraud and false statement statutes.The fraud provisions of the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health InformationTechnology for Economic and Clinical Health Act, or HITECH, among other things, imposes criminal and civil liability for knowingly and willfullyexecuting a scheme to defraud any healthcare benefit program, including private third party payors and knowingly and willfully falsifying, concealing orcovering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcarebenefits, items or services.The federal Physician Payment Sunshine Act, being implemented as the Open Payments Program, which requires manufacturers of drugs, devices,biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certainexceptions) to report annually to CMS information related to direct or indirect payments and other transfers of value to physicians and teaching hospitals, aswell as ownership and investment interests held in the company by physicians and their immediate family members. Beginning in 2022, applicablemanufacturers also will be required to report information regarding payments and transfers of value provided to physician assistants, nurse practitioners,clinical nurse specialists, certified nurse anesthetists and certified nurse-midwives.Many states have adopted analogous laws and regulations, including state anti-kickback and false claims laws, which may apply to items or servicesreimbursed under Medicaid and other state programs or, in several states, regardless of the payor. Several states have enacted legislation requiringpharmaceutical companies to, among other things, establish marketing compliance programs; file periodic reports with the state, including reports on giftsand payments to individual health care providers; make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities; and/orregister their sales representatives. Some states prohibit pharmacies and other healthcare entities from providing specified physician prescribing data topharmaceutical companies for use in sales and marketing. Some states prohibit other specified sales and marketing practices, including the provision of gifts,meals, or other items to certain health care providers, and/or offering co-pay support to patients for certain prescription drugs. All of our activities arepotentially subject to federal and state consumer protection and unfair competition laws. In addition, in order to distribute products commercially, we mustcomply with state laws that require the registration of manufacturers and wholesale distributors of pharmaceutical products in a state, including, in somestates, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.In addition, we may be subject to data privacy and security laws and regulations by both the federal government and the states in which we conductour business. The legislative and regulatory landscape for privacy and data protection continues50Table of Contentsto evolve, and there has been an increasing focus on privacy and data protection issues which may affect our business. Numerous federal and state laws andregulations, including state security breach notification laws, state health information privacy laws and federal and state consumer protection laws, governthe collection, use, disclosure, and protection of health-related and other personal information. Failure to comply with such laws and regulations could resultin government enforcement actions and create liability for us (including the imposition of significant civil or criminal penalties), private litigation and/oradverse publicity that could negatively affect our business. HIPAA, as amended by HITECH and its implementing regulations, imposes requirements relatingto the privacy, security and transmission of individually identifiable health information. HITECH also increased the civil and criminal penalties that may beimposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions fordamages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions.We may obtain health information from third parties, such as research institutions, that are subject to privacy and security requirements under HIPAA.Although we are not directly subject to HIPAA - other than with respect to providing certain employee benefits - we could potentially be subject to criminalpenalties if we, our affiliates, or our agents knowingly obtain or disclose individually identifiable health information maintained by a HIPAA-covered entityin a manner that is not authorized or permitted by HIPAA. In addition, state laws govern the privacy and security of health information in specifiedcircumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts. Otherjurisdictions, including Canada, have corresponding laws and regulations governing the handling of personal information and third party communicationsthat may be more or less stringent than those of the United States. In Canada, such laws include the Personal Information Protection and ElectronicDocuments Act, similar provincial legislation regarding privacy and personal health information and anti-spam legislation, wherein the failure to comply orbreaches can result in notification requirements or corrective action, including civil and criminal fines and sanctions.In the United States, our activities are potentially subject to additional regulation by various federal, state and local authorities in addition to theFDA, including CMS, other divisions of HHS (for example, the Office of Inspector General), the DOJ and individual United States Attorney offices within theDOJ, and state and local governments.If we participate in the Medicaid drug rebate program, we will have certain price reporting obligations to the Medicaid drug rebate program, and wemay have obligations to report average sales price, or ASP, figures to the Medicare program. Under the Medicaid drug rebate program, we would be requiredto pay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaidprogram as a condition of having federal funds being made available to the states for our drugs under Medicaid and Medicare Part B. Those rebates are basedon pricing data reported by us on a monthly and quarterly basis to CMS. These data include average manufacturer price, or AMP and, in the case of innovatorproducts, the best price for each drug which, in general, represents the lowest price available from the manufacturer to any entity in the United States in anypricing structure, calculated to include all sales and associated rebates, discounts and other price concessions.Federal law also requires that a company that participates in the Medicaid drug rebate program report ASP information each quarter to CMS forcertain categories of drugs that are paid under Part B of the Medicare program. Manufacturers calculate ASP based on a statutorily defined formula andinterpretations of the statute by CMS. CMS uses these submissions to determine payment rates for drugs under Medicare Part B and the resulting Medicarepayment rate.Federal law requires that any company that participates in the Medicaid drug rebate program also participate in the Public Health Service’s 340Bdrug pricing program in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B. The 340B drug pricingprogram requires participating manufacturers to agree to charge statutorily-defined covered entities no more than the 340B “ceiling price” for themanufacturer’s covered outpatient drugs. The Health Resources and Services Administration, or HRSA, which administers the 340B drug pricing program,issued a final regulation regarding the calculation of the 340B ceiling price and the imposition of civil monetary penalties on manufacturers that knowinglyand intentionally overcharge covered entities, which became effective on January 1, 2019. HRSA also has begun to implement a ceiling price reportingrequirement during the first quarter of 2019, pursuant to which manufacturers must report the 340B ceiling prices for their covered outpatient drugs on aquarterly basis.In addition, in order to be eligible to have its products paid for with federal funds under the Medicaid and Medicare Part B programs and purchasedby certain federal agencies and grantees, a manufacturer also must participate in the Department of Veterans Affairs Federal Supply Schedule, or FSS, pricingprogram, established by Section 603 of the Veterans Health Care Act of 1992. Under this program, the manufacturer is obligated to make its “covered drugs”(biologics or innovator drugs) available for procurement on an FSS contract and charge a price to four federal agencies, Department of Veterans Affairs,Department of Defense, Public Health Service, and Coast Guard, that is no higher than the statutory federal ceiling price. The requirements under the 340Band FSS programs could reduce the revenue we may generate from any products that are commercialized in the future and could adversely affect our businessand operating results.51Table of ContentsPricing and rebate calculations vary among products and programs. The calculations are complex and are often subject to interpretation bymanufacturers, governmental or regulatory agencies, and the courts. The Medicaid rebate amount for each manufacturer is computed each quarter based onthe manufacturer’s submission to CMS of its current AMP and, in the case of innovator products, best price figures, for the quarter. If we participate in theMedicaid drug rebate program and become aware that our reporting for a prior quarter was incorrect, or has changed, we will be obligated to resubmit thecorrected data for a period not to exceed twelve quarters from the quarter in which the data originally were due. Such restatements and recalculations wouldincrease our costs for complying with the laws and regulations governing the Medicaid drug rebate program. Any corrections to our rebate calculations couldresult in an overage or underage in our rebate liability for past quarters, depending on the nature of the correction. Price recalculations also may affect theceiling price at which we would be required to offer our products to certain covered entities, such as safety-net providers, under the 340B drug pricingprogram, and we may be obligated to issue refunds to covered entities.If we participate in the Medicaid drug rebate program or our products are covered under Medicare Part B, we will be liable for errors associated withour submission of pricing data. We cannot assure you that our submissions, if we participate in these programs, will not be found by CMS to be incomplete orincorrect. In addition to retroactive rebates and the potential for 340B program refunds, if we are found to have knowingly submitted false AMP, ASP, or bestprice information to the government, we may be liable for civil monetary penalties per item of false information. If we are found to have made amisrepresentation in the reporting of our ASP, the Medicare statute provides for civil monetary penalties for each misrepresentation for each day in which themisrepresentation was applied. Civil monetary penalties also can be applied if we are found to have intentionally charged 340B covered entities more thanthe statutorily mandated ceiling price. Our failure to submit monthly/quarterly AMP, ASP, and best price data on a timely basis could result in a civilmonetary penalty per day for each day the information is late beyond the due date. Such failure also could be grounds for CMS to terminate our Medicaiddrug rebate agreement, pursuant to which we would participate in the Medicaid program. In the event that CMS terminates our rebate agreement, federalpayments may not be available under Medicaid or Medicare Part B for our covered outpatient drugs that we are able to successfully commercialize.Because of the breadth of these laws and the narrowness of available statutory and regulatory exemptions, it is possible that some of our businessactivities could be subject to challenge under one or more of such laws. If our operations are found to be in violation of any of the federal and state lawsdescribed above or any other governmental regulations that apply to us, we may be subject to penalties, including (depending on the applicable law)criminal and significant civil monetary penalties, damages, fines, imprisonment, exclusion from participation in government programs, injunctions, recall orseizure of products, total or partial suspension of production, denial or withdrawal of pre-marketing product approvals, private ‘‘qui tam’’ actions brought byindividual whistleblowers in the name of the government or refusal to allow us to enter into supply contracts, including government contracts, and thecurtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations. To theextent that any of our products are sold in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance,applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws, and implementation of corporate compliance programs andmore extensive reporting of payments or transfers of value to healthcare professionals.In the E.U., interactions between pharmaceutical companies and physicians are also governed by strict laws, regulations, industry self-regulationcodes of conduct and physicians’ codes of professional conduct in the individual E.U. Member States. The provision of benefits or advantages to physiciansto induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is prohibited. The provision ofbenefits or advantages to physicians is also governed by the national anti-bribery laws of the E.U. Member States. One example is the UK Bribery Act 2010.This act applies to any company incorporated in or “carrying on business” in the UK, irrespective of where in the world the alleged bribery activity occurs.Violation of these laws could result in substantial fines and imprisonment.The national laws of certain E.U. Member States require payments made to physicians to be publicly disclosed. Moreover, the European Federationof Pharmaceutical Industries and Associations, or EFPIA Code on disclosure of transfers of value from pharmaceutical companies to healthcare professionalsand healthcare organizations imposes a general obligation on members of EFPIA or related national industry bodies to disclose transfers of value tohealthcare professionals. In addition, agreements with physicians must often be the subject of prior notification and approval by the physician’s employer,his/her competent professional organization, and/or the competent authorities of the individual E.U. Member States. These requirements are provided in thenational laws, industry codes, or professional codes of conduct, applicable in the individual E.U. Member States.If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, warning letters or untitled letters,injunctions, civil, administrative, or criminal penalties, monetary fines or imprisonment, suspension or withdrawal of regulatory approvals, suspension ofongoing clinical studies, refusal to approve pending52Table of Contentsapplications or supplements to applications filed by us, suspension or the imposition of restrictions on operations, product recalls, the refusal to permit theimport or export of our products or the seizure or detention of products.Environmental and safety lawsWe are subject to a variety of federal, provincial and local regulations relating to the use, handling, storage and disposal of hazardous materials,including chemicals and radioactive and biological materials. Our operations involve such hazardous materials and produce such hazardous waste products.Although we believe that our safety procedures for handling and disposing of these materials comply with the standards prescribed by federal, provincial andlocal regulations, the risk of accidental contamination or injury from these materials cannot be eliminated. Radioactive materials in Canada come underfederal jurisdiction. Canada’s Nuclear Safety and Control Act 1997 c.9 contains a general prohibition against any activity, including possession ofradioactive material, except in accordance with the terms and conditions set out in a federal license issued by the Canadian Nuclear Safety Commission. TheNuclear Substances and Radiation Devices Regulation does however, exempt licensing requirements for small quantities of radioactive substances that eithermeet concentrations set out in a schedule to the Regulation or, for radioactive substances not set out in the schedule, that meet certain regulatory criteria. Ouroperations do not currently require a federal license issued by the Canadian Nuclear Safety Commission. Our operations in Canada may be subject to licenseapprovals, notification requirements and investigation and enforcement for air and water and waste matters.Corporate History - Acquisition of ViventiaWe were incorporated under the laws of the State of Delaware in 2008. We were formerly known as Denovo Therapeutics, Inc. and Newco LS14, Inc.before changing our name to Eleven Biotherapeutics, Inc in February 2010 and again to Sesen Bio, Inc. in May 2018.On September 20, 2016, we entered into a Share Purchase Agreement with Viventia, the shareholders of Viventia named therein - collectivelyreferred to herein as the Selling Shareholders - and, solely in its capacity as seller representative, Clairmark, an affiliate of Leslie Dan, one of our directors,pursuant to which we agreed to and simultaneously completed the acquisition of all of the outstanding capital stock of Viventia from the SellingShareholders, referred to herein as the Acquisition. In connection with the closing of the Acquisition, we issued 4,013,431 shares of our common stock to theSelling Shareholders according to their pro rata share of Viventia’s then-outstanding shares of common stock, which represented approximately 19.9% of ourvoting power as of immediately prior to the issuance of such shares of common stock.In connection with the Acquisition, we are obligated to pay to the sellers certain post-closing contingent cash payments upon the achievement ofspecified milestones and based upon net sales, in each case subject to the terms and conditions set forth in the acquisition agreement, including: (i) a one-time milestone payment of $12.5 million payable upon the first sale of Vicinium (referred to herein as the "Purchased Product"), in the United States; (ii) aone-time milestone payment of $7.0 million payable upon the first sale of the Purchased Product in any one of certain specified European countries; (iii) aone-time milestone payment of $3.0 million payable upon the first sale of the Purchased Product in Japan; and (iv) and quarterly earn-out payments equal totwo percent (2%) of net sales of the Purchased Product during specified earn-out periods. Such earn-out payments are payable with respect to net sales in acountry beginning on the date of the first sale in such country and ending on the earlier of (i) December 31, 2033 and (ii) fifteen years after the date of suchsale, subject to early termination in certain circumstances if a biosimilar product is on the market in the applicable country.Under the Share Purchase Agreement, we, our affiliates, licensees and subcontractors are required to use commercially reasonable efforts, for the firstseven years following the closing of the Acquisition, to achieve marketing authorizations throughout the world and, during the applicable earn-out period, tocommercialize the Purchased Product in the United States, France, Germany, Italy, Spain, United Kingdom, Japan, China and Canada.Corporate Information and Access to SEC ReportsOur principal executive offices are located at 245 First Street, Suite 1800, Cambridge, Massachusetts 02142, our telephone number is (617) 444-8550 and our website address is www.sesenbio.com. We make our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K,and amendments to those reports, available free of charge in the “Investors” section of our website as soon as reasonably practicable after we file these reportswith the SEC. We routinely post these reports, recent news and announcements, financial results and other important information about our business on ourwebsite at www.sesenbio.com. Information contained on our website is not a part of this annual report.53Table of ContentsIn addition, the SEC maintains an Internet website at http://www.sec.gov that contains reports, proxy and information statements, and otherinformation regarding issuers that file electronically with the SEC.EmployeesAs of December 31, 2018, we had 24 full-time employees and no part-time employees, ten hold Ph.D. degrees, one is a medical doctor and one is aveterinary doctor. This number consists of five employees engaged in administration, seven employees engaged in clinical/regulatory activities, sixemployees engaged in research and development, three employees engaged in operations (two in manufacturing and one in facility/engineering) and threeemployees engaged in quality and support. Two of our employees are located in our corporate headquarters in Boston, twelve of our employees are located inour Winnipeg facility, and ten of our employees are located in our Philadelphia office. We have no collective bargaining agreements with our employees andnone are represented by labor unions. We have not experienced any work stoppages. We believe our relationship with our employees is satisfactory.54Table of ContentsItem 1A.Risk FactorsRisks Related to Our Financial Position and Need for Additional CapitalWe have incurred significant losses since our inception and anticipate that we will continue to incur losses for the foreseeable future.Since inception, we have incurred significant operating losses and expect to continue to incur operating losses for the foreseeable future. We had a net loss of$33.7 million for the year ended December 31, 2018, a net loss of $29.0 million for the year ended December 31, 2017 and a net income of $1.9 million forthe year ended December 31, 2016. We had net income of $1.9 million for the year ended December 31, 2016 due to the $29.6 million of revenue for ourLicense Agreement with Roche. As of December 31, 2018, we had an accumulated deficit of $186.0 million. To date, we have financed our operationsprimarily through private placements of our common stock and preferred stock and convertible bridge notes, venture debt borrowings, our initial publicoffering, or IPO, and our follow-on public offering, sales effected in an "at-the-market" facility, through our License Agreement with Roche and, to a lesserextent, from a collaboration. The majority of our revenue to date has been licensing revenue from our License Agreement with Roche and collaborationrevenue. We have devoted substantially all of our financial resources and efforts to research and development activities. We are still in the early stages ofdevelopment of certain of our product candidates, and we have not completed development of any product candidates. We expect to continue to incursignificant expenses and operating losses over the next several years. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year.We will incur substantial expenses if and as we:•continue our Phase 3 clinical trial for Vicinium for the treatment of high-risk NMIBC;•continue the research and pre-clinical and clinical development of our other product candidates;•seek and conduct combination trials of one or more of our product candidates;•seek to discover and develop additional product candidates;•in-license or acquire the rights to other products, product candidates or technologies;•seek marketing approvals for any product candidates that successfully complete clinical trials;•establish sales, marketing and distribution capabilities and scale up and validate external manufacturing capabilities to commercialize anyproduct candidates for which we may obtain marketing approval;•maintain, expand and protect our intellectual property portfolio;•add equipment and physical infrastructure to support our research and development;•complete the technology transfer of Vicinium bulk drug substance manufacturing to Fujifilm;•hire additional clinical, quality control, scientific and management personnel;•expand our operational, financial and management systems and personnel; and•develop our internal control environment for the additional compliance level of Section 404(b) of the Sarbanes-Oxley Act.Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing oramount of increased expenses or when, or if, we will be able to achieve profitability. Our expenses will increase substantially if:•we are required by the FDA, the EMA or Health Canada to perform studies or clinical trials in addition to those currently expected; or•if there are any delays in enrollment of patients in, or completing our clinical trials or the development of any product candidates that wemay develop.With the exception of specified regulatory, development and commercial milestones under our License Agreement with Roche, we currently have no sourceof product revenue and may never become profitable.55Table of ContentsOur ability to become and remain profitable depends on our ability to generate revenue. Although we may be entitled to certain licensing fees related tospecific regulatory, development and commercial milestones for EBI-031 under our License Agreement with Roche, we have not commercialized any of ourproduct candidates. We do not expect to generate significant revenue from the development of our product candidates unless and until we obtain marketingapproval for, and commercialize, Vicinium or our other product candidates that we may develop, in-license or acquire in the future. This would require us tobe successful in a range of challenging activities, including:•successfully completing development activities, including clinical trial design and enrollment of a sufficient number of patients in ourclinical trials and completion of the necessary clinical trials;•completing and submitting BLAs to the FDA and obtaining regulatory approval for indications for which there is a commercial market;•completing and submitting applications to, and obtaining regulatory approval from, foreign regulatory authorities, including HealthCanada and the European Commission;•establishing sales, marketing and distribution capabilities, either ourselves or through collaborations or other arrangements with thirdparties, to effectively market and sell our product candidates;•achieving an adequate level of market acceptance of our product candidates;•successfully commercializing any product candidates, if approved;•protecting our rights to our intellectual property portfolio;•ensuring the manufacture of commercial quantities of our product candidates;•finding suitable partners to help us develop certain of our product candidates and market, sell and/or distribute any of our products thatreceive regulatory approval in other markets; and•obtaining adequate pricing, coverage and reimbursement from third parties, including government and private payors.We are only in the preliminary stages of most of these activities. We may never succeed in these activities and, even if we do, may never generate revenuesthat are significant enough to achieve profitability.Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remainprofitable would depress the value of our company and could impair our ability to raise capital, expand our business, maintain our research and developmentefforts, diversify our product offerings or even continue our operations. A decline in the value of our company could also cause our stockholders to lose all orpart of their investment.We will need substantial additional funding. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our productdevelopment programs or commercialization efforts.We are devoting substantial financial resources to our ongoing and planned activities including functions associated with operating as a public company.We expect to continue to spend substantial amounts of funds in connection with our ongoing activities, particularly as we continue our Phase 3 clinical trialfor Vicinium for the treatment of high-risk NMIBC and continue research and development activities. In addition, if we obtain regulatory approval for any ofour product candidates, we would need to devote substantial financial resources to commercialization efforts, including product manufacturing, marketing,sales and distribution. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable toraise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or any futurecommercialization efforts.Our future capital requirements will depend on many factors, including:•the initiation, progress, timing, costs and results of clinical trials for our product candidates;•the scope, progress, results and costs of pre-clinical development and laboratory testing of our pre-clinical product candidates;•our ability to establish collaborations on favorable terms, if at all, particularly manufacturing, marketing and distribution arrangements forour product candidates;•the costs and timing associated with our manufacturing process and technology transfer to FujiFilm;•the costs and timing of the implementation of commercial-scale manufacturing activities;56Table of Contents•the costs and timing of establishing sales, marketing and distribution capabilities for any product candidates for which we may receiveregulatory approval;•the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights anddefending any intellectual property-related claims;•our obligation to make milestone, royalty and other payments to third party licensors under our licensing agreements;•the extent to which we in-license or acquire rights to other products, product candidates or technologies;•the outcome, timing and cost of regulatory review by the FDA and comparable foreign regulatory authorities, including the potential for theFDA or comparable foreign regulatory authorities, including Health Canada or the EMA, to require that we perform more studies than thosethat we currently expect;•the effect of competing technological and market developments; and•the revenue, if any, received from commercial sales of any product candidates for which we receive regulatory approval.We believe that our cash and cash equivalents of $50.4 million as of December 31, 2018, will be sufficient to fund our current operating plan into 2020;however, we have based this estimate on assumptions that may prove to be wrong, and our capital resources may be utilized faster than we currently expect.Identifying potential product candidates and conducting pre-clinical studies and clinical trials is a time-consuming, expensive and uncertain process thattakes years to complete, and we may never generate the necessary data or results required to obtain regulatory approval and achieve product sales. Ourcommercial revenues, if any, will be derived from sales of any product candidates that we successfully develop, none of which we expect to be commerciallyavailable in the near term, if at all. In addition, if approved, any product candidate that we develop or any product that we in-license may not achievecommercial success. Accordingly, we will need to obtain substantial additional financing to achieve our business objectives. Adequate additional financingmay not be available to us on acceptable terms, or at all. In addition, we may seek additional capital due to favorable market conditions or strategicconsiderations, even if we believe we have sufficient funds for our current or future operating plans.Our independent registered public accounting firm has included an explanatory paragraph relating to our ability to continue as a going concern in itsreport on our audited financial statements included in our Annual Report on Form 10-K.Our report from our independent registered public accounting firm for the year ended December 31, 2018 includes an explanatory paragraph stating that ourrecurring losses from operations and insufficient cash resources raise substantial doubt about our ability to continue as a going concern. If we are unable toobtain adequate financing or engage in another strategic transaction on acceptable terms and when needed, our business, prospects, financial condition andresults of operations will be materially and adversely affected and we may be unable to continue as a going concern. While we believe that our cash and cashequivalents of $50.4 million at December 31, 2018 will be sufficient to fund our current operating plan into 2020, given our planned expenditures for thenext several years, we and our independent registered public accounting firm have concluded that there is still a substantial doubt regarding our ability tocontinue as a going concern. If we are unable to continue as a going concern, we may have to liquidate our assets and may receive less than the value atwhich those assets are carried on our audited financial statements, and it is likely that investors will lose all or a part of their investment. If we seek additionalfinancing to fund our business activities in the future and there remains substantial doubt about our ability to continue as a going concern, investors or otherfinancing sources may be unwilling to provide additional funding to us on commercially reasonable terms or at all.Future sales and issuances of shares of our common stock or rights to purchase shares of our common stock, including pursuant to our 2014 StockIncentive Plan and 2009 Stock Incentive Plan, could result in additional dilution of the percentage ownership of our stockholders, restrict our operationsor require us to relinquish rights to our technologies or product candidates.Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debtfinancings, government or other third-party funding, collaborations, strategic alliances, licensing arrangements, other commercial arrangements andmarketing and distribution arrangements. We do not have any committed external source of funds other than the amounts payable under the LicenseAgreement with Roche. To the extent that we raise additional capital through the sale of equity or convertible debt securities, our stockholders’ ownershipinterest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect our stockholders’57Table of Contentsrights as holders of our common stock. For example, as of December 31, 2018, and subject to adjustment upon certain corporate events, including stockdividends, stock splits and distributions of cash, up to 9,259,632shares of our common stock could be issuable by us, with a weighted average exercise priceof $1.17 per share, in connection with the exercise of our outstanding common stock purchase warrants.We have also adopted the 2014 Stock Incentive Plan, or the 2014 Plan, to enable us and our subsidiaries to recruit and retain highly qualified employees,directors and consultants, provide those individuals with an incentive for productivity, and provide those individuals with an opportunity to share in ourgrowth and value. As of December 31, 2018, we had 2,000,937 shares of common stock available for grant under the 2014 Plan. Future equity incentivegrants and issuances of shares of common stock under the 2014 Plan, or other grants outside of the 2014 Plan pursuant to inducement equity awards, mayhave an adverse effect on the market price of shares of our common stock.Further, debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to takespecific actions, such as incurring additional debt, making capital expenditures or declaring dividends.If we raise additional funds through government or other third-party funding, collaborations, strategic alliances, licensing arrangements or marketing anddistribution arrangements, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates orgrant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may berequired to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market products orproduct candidates that we would otherwise prefer to develop and market ourselves.Our limited operating history may make it difficult for our stockholders to evaluate the success of our business to date and to assess our future viability.We are an early-stage company. We were incorporated and commenced active operations in early 2008, and our operations to date have been limited toorganizing and staffing our company, acquiring rights to intellectual property, business planning, raising capital, developing our technology, identifyingpotential product candidates, undertaking pre-clinical studies and conducting clinical trials. All of our product candidates which we are currently pursuingare still in clinical or pre-clinical development. We have not yet demonstrated our ability to successfully complete clinical development of any productcandidate, obtain marketing approvals, manufacture at commercial scale, or arrange for a third party to do so on our behalf, or conduct sales, marketing anddistribution activities necessary for successful product commercialization. Consequently, any predictions about our future success or viability may not be asaccurate as they could be if we had a longer operating history.In addition, as a new business, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We willneed to transition at some point from a company with a research and development focus to a company capable of supporting commercial activities. We maynot be successful in such a transition.We expect our financial condition and operating results to continue to fluctuate significantly from quarter-to-quarter and year-to-year due to a variety offactors, many of which are beyond our control. Accordingly, our stockholders should not rely upon the results of any quarterly or annual periods asindications of future operating performance.Business disruptions could seriously harm our future revenues and financial condition and increase our costs and expenses.Our operations could be subject to earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extremeweather conditions, medical epidemics and other natural or man-made disasters or business interruptions. The occurrence of any of these business disruptionscould seriously harm our operations and financial condition and increase our costs and expenses. The ultimate impact on us and our general infrastructure ofbeing in certain geographical areas is unknown, but our operations and financial condition could suffer in the event of a fire or other natural disaster.Risks Related to the Discovery and Development of Our Product CandidatesWe are dependent on our lead product candidate, Vicinium for the treatment of high-risk NMIBC. If we are unable to obtain marketing approval for orsuccessfully commercialize our lead product candidate, either alone or through a collaboration, or experience significant delays in doing so, our businesscould be materially harmed.58Table of ContentsWe currently have no products approved for sale and have invested a significant portion of our efforts and financial resources in the development ofVicinium for the treatment of patients with high-risk NMIBC. Our prospects are substantially dependent on our ability to obtain marketing approval for andsuccessfully commercialize Vicinium. The success of our lead product candidate will depend, among other things, on our ability to design and successfullycomplete clinical trials for Vicinium. The clinical trial process is uncertain, and failure of one or more clinical trials can occur at any stage of testing. Forexample, in 2009, Viventia put its development of Vicinium on hold due to the uncertainty of the standard of care for bladder cancer. Additionally, we havedeferred further development of Vicinium for the treatment of SCCHN, our product candidate for the treatment of patients with recurrent, locally advanced ormetastatic EpCAM-expressing SCCHN, and VB6-845d, our lead systemically-administered product candidate being developed for the treatment of multipletypes of EpCAM-positive solid tumors, in order to focus our efforts and our resources on our ongoing development of Vicinium for the treatment of high-riskNMIBC. EBI-031 is also in the early stages of development. We submitted an IND for EBI-031 for the treatment of diabetic macular edema, or DME, anduveitis in June 2016. This IND was allowed to go into effect on July 7, 2016 and enabled initiation of clinical development of this product candidate.Subsequently, we licensed EBI-031 pursuant to the License Agreement with Roche, who will now be responsible for the development and potentialcommercialization of EBI-031.In addition to the successful completion of clinical trials, the success of Vicinium, VB6-845d and EBI-031 will also depend on several other factors,including the following:•receipt of marketing approvals from the FDA, Health Canada, the European Commission or comparable foreign regulatory authorities;•performance of our future collaborators, if any;•extent of any required post-marketing approval commitments to applicable regulatory authorities;•obtaining and maintaining patent, trade secret protection and regulatory exclusivity, both in the United States and internationally;•protection of our rights in our intellectual property portfolio;•launch of commercial sales, if and when marketing approval is received;•demonstration of an acceptable safety profile prior to and following any marketing approval;•marketplace acceptance, if and when approved, by patients, the medical community and third-party payors;•establishing and maintaining pricing sufficient to realize a meaningful return on our investment; and•competition with other therapies.If we (or, in the case of EBI-031, Roche) are unable to develop, receive marketing approval for, or successfully commercialize Vicinium for the treatment ofhigh-risk NMIBC, Vicinium for the treatment of SCCHN, VB6-845d or EBI-031, or experience delays as a result of any of these factors or otherwise, ourbusiness could be materially harmed.If clinical trials of any product candidate that we develop fail to demonstrate safety and efficacy to the satisfaction of the FDA, Health Canada, the EMAor other regulatory authorities or do not otherwise produce favorable results, we may incur additional costs or experience delays in completing, orultimately be delayed or unable to complete, the development and commercialization of any product candidate.Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we must complete pre-clinical development and thenconduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Clinical testing is expensive, difficult to designand implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. Theoutcome of pre-clinical studies and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do notnecessarily predict final results. Moreover, pre-clinical and clinical data are often susceptible to varying interpretations and analyses, and many companiesthat have believed their product candidates performed satisfactorily in pre-clinical studies and clinical trials have nonetheless failed to obtain marketingapproval of their product candidates. For example, in January 2016, we announced top-line results from our Phase 3 clinical trial of isunakinra in patientswith severe allergic conjunctivitis. In this trial, there was no statistically significant difference between the isunakinra treated group and the vehicle controlgroup on the primary endpoint of ocular itching or on any secondary endpoints.Many compounds that initially showed promise in early-stage testing for treating cancer have later been found to not be effective treatments or to causeside effects that prevented further development of the compound. The therapeutic efficacy59Table of Contentsand safety profiles of our product candidates have not been demonstrated in humans, and we may not be able to successfully develop and commercializeour product candidates.Our product candidates are novel and their potential benefit is unproven. Our ability to generate revenues from our product candidates, which we do notexpect will occur in the short term, if ever, will depend heavily on the successful development, approval and commercialization, if achieved, of one or moreof our product candidates. For example, our product candidates may not prove to be effective treatments for the cancer targets they are being designed to actagainst and may not demonstrate in patients any or all of the pharmacological data points that may have been demonstrated in pre-clinical studies andprevious clinical trials. Our product candidates may interact with human biological systems in unforeseen, ineffective or harmful ways. If our productcandidates are associated with undesirable side effects or have characteristics that are unexpected, we may need to abandon their development or limitdevelopment to certain uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptablefrom a risk-benefit perspective. Many compounds that initially showed promise in early-stage testing for treating cancer have later been found to not beeffective treatments or to cause side effects that prevented further development of the compound. As a result of these and other risks described herein that areinherent in the development of novel therapeutic agents, we may never successfully develop, enter into or maintain third party licensing or collaborationtransactions with respect to, or successfully commercialize our product candidates, in which case we will not achieve profitability and the value of our sharesof common stock may decline.We may expend our limited resources to pursue development of a particular product candidate or indication and fail to capitalize on product candidatesor indications that have a greater likelihood of clinical success or commercial potential.Because we have limited financial and managerial resources, we focus on research programs and product candidates that we identify for specific indications.As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater likelihoodof clinical success or commercial potential. For example, we previously invested a significant portion of our efforts and financial resources in thedevelopment of isunakinra for the treatment of patients with dry eye disease and allergic conjunctivitis. Notwithstanding this significant investment, basedon the results from our completed Phase 3 clinical trials in dry eye disease and allergic conjunctivitis, we do not plan to pursue further development ofisunakinra. Additionally, in September 2017, we deferred further development of Vicinium for the treatment of SCCHN and VB6-845d in order to focus ourefforts and our resources on our ongoing development of Vicinium for the treatment of high-risk NMIBC.Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending onresearch and development programs and product candidates for specific indications may not yield any commercially viable products. In addition, if we donot accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that productcandidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain soledevelopment and commercialization rights to such product candidate.If we experience any of a number of possible unforeseen events in connection with our clinical trials, potential marketing approval or commercializationof our product candidates could be delayed or prevented.We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive marketing approvalor commercialize any product candidates that we may develop, including:•clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, toconduct additional clinical trials or abandon product development programs;•the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinicaltrials may be slower or more challenging than we anticipate or patients may drop out of these clinical trials at a higher rate than weanticipate;•our third-party contractors may fail to comply with regulatory requirements, including GCPs or meet their contractual obligations to us in atimely manner, or at all;•inspection of the clinical trial operations, trial sites or manufacturing facility by the FDA or other comparable foreign regulatory authoritiessuch as Health Canada, or the competent authorities of the E.U. Member States, could result in findings of non-compliance and theimposition of a clinical suspension or termination;•regulators or IRBs/Ethics Committees may delay or not authorize us or our investigators to commence a clinical trial or conduct a clinicaltrial at a prospective trial site;60Table of Contents•we may experience delays or fail to reach agreement with the FDA or a comparable foreign regulatory authority, including Health Canadaor the competent authorities of the E.U. Member States, on a trial design that we are able to execute;•we may be unable to identify and maintain a sufficient number of trial sites, many of which may already be engaged in other clinical trialprograms, including for the same indications as our clinical trials;•we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols withprospective trial sites;•trial sites and investigators may deviate from clinical trial protocols or otherwise fail to conduct the trial in accordance with regulatoryrequirements, and investigators may drop out of the clinical trial;•trial sites may withdraw from our clinical trials, including as a result of changing standards of care or ineligibility of a site to participate inour clinical trials;•we may decide, or regulators or IRBs/Ethics Committees or other reviewing entities, including comparable foreign regulatory authoritiessuch as Health Canada or the competent authorities of the E.U. Member States, may require us to suspend or terminate clinical research forvarious reasons, including noncompliance with regulatory requirements including GCPs or a finding that the patients are being exposed tounacceptable health risks;•the cost of clinical trials of our product candidates may be greater than we anticipate;•we may receive feedback from DSMBs or the FDA, or a comparable foreign regulatory authority, including Health Canada or the competentauthorities of the E.U. Member States, that might require modification to the protocol for the clinical trial or performance of additionalstudies before clinical trials may continue;•as a clinical trial proceeds, or as the results of earlier stage studies or concurrent studies become available, we may determine that we needto modify the protocol and/or other aspects of the clinical trial before it may continue;•the FDA, a comparable foreign regulatory authority, including Health Canada, or the competent authorities of the E.U. Member States, orwe may decide to, or a DSMB may recommend to, suspend or terminate clinical trials at any time for safety issues or for any other reason;•the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may beinsufficient or inadequate;•our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators orIRBs/Ethics Committees to suspend or terminate the trials;•lack of adequate funding to continue a clinical trial, including the incurrence of unforeseen costs due to enrollment delays, requirements toconduct additional clinical trials or increased expenses associated with the services of our CROs and other third parties; and•changes in applicable laws, governmental regulations or administrative actions.We rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials, and while we have agreements governing theiractivities, we have limited influence over their actual performance. Any delays in completing our clinical trials will increase our costs, slow down ourdevelopment and regulatory submission process for our product candidates and jeopardize our ability to obtain regulatory approval, commence commercialsales and generate revenues, if our product candidates are ultimately approved.Further, conducting clinical trials in foreign countries, as we have done historically for Vicinium (both for the treatment of high-risk NMIBC and for thetreatment of SCCHN) and as we may decide to do in the future, presents additional risks that may delay completion of our clinical trials. These risks includethe failure of enrolled patients in foreign countries to adhere to clinical protocol as a result of differences in healthcare services or cultural customs,managing additional administrative burdens associated with foreign regulatory frameworks, as well as political and economic risks relevant to such foreigncountries.If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unableto successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not favorable or are only modestlyfavorable or if there are safety concerns, we may:•be delayed in obtaining marketing approval for our product candidates;61Table of Contents•not obtain marketing approval at all;•obtain approval for indications or patient populations that are not as broad as intended or desired;•obtain approval with labeling that includes significant use or distribution restrictions or safety warnings, or is subject to a REMS;•be subject to additional post-marketing testing requirements; or•have the product removed from the market after obtaining marketing approval.Our product development costs will also increase if we experience delays in testing or marketing approvals. We do not know whether any of our pre-clinicalstudies or clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Significant pre-clinical or clinical trialdelays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates or allow our competitors tobring products to market before we do and impair our ability to successfully commercialize our product candidates.If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary regulatory approvals could be delayed orprevented.We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of patients toparticipate in these trials as required by the FDA or similar regulatory authorities outside the United States, including Health Canada or the EMA. We havepreviously experienced difficulties with clinical trial enrollment and retention, which led to the early termination of our Phase 3 trial of Vicinium for thetreatment of SCCHN in 2008, and we may experience difficulties in patient enrollment in our clinical trials in the future for a variety of reasons.Subject enrollment is affected by a number of factors, including:•the severity of the disease under investigation;•the eligibility criteria for the clinical trial in question;•the size of the patient population for the disease;•the size of the patient population required for statistically significant analysis of the clinical trial’s primary endpoints;•the design of the clinical trial;•the clinicians' and patients' perceived risks and benefits of the product candidate under study, including relative to alternative treatments;•the efforts to facilitate timely enrollment in clinical trials;•the patient referral practices of physicians;•any ongoing clinical trials conducted by competitors for the same indication;•the risk that patients enrolled in clinical trials will drop out of the clinical trials before completion;•the ability to monitor patients adequately during and after treatment; and•the proximity and availability of clinical trial sites for prospective patients.Further, our ability to successfully initiate, enroll and complete a clinical trial in any foreign country, should we decide to do so, is subject to numerous risksunique to conducting business in foreign countries, including:•difficulty in establishing or managing relationships with CROs and physicians;•different or additional standards for the conduct of clinical trials;•absence in some countries of established groups with sufficient regulatory expertise for review of the protocols associated with our productcandidates;•ensuring that clinical trial quality is sufficient to meet the standards of the FDA or other regulatory authorities;•our inability to locate qualified local consultants, physicians and partners; and•the potential burden of complying with a variety of foreign laws, medical standards and regulatory requirements, including the regulation ofpharmaceutical and biotechnology products and treatments.62Table of ContentsIn addition, our clinical trials will compete with other clinical trials for other product candidates that are in the same therapeutic areas as our productcandidates, and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in ourtrials may instead opt to enroll in a trial being conducted by one of our competitors. Since the number of qualified clinical investigators is limited, we expectto conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patients who areavailable for our clinical trials in such clinical trial site. Moreover, because our product candidates represent a departure from more commonly used methodsfor cancer treatment, potential patients and their doctors may be inclined to use conventional therapies, such as chemotherapy, rather than enroll patients inany of our clinical trials.Our inability to enroll a sufficient number of patients for our clinical trials would result in significant delays, could require us to abandon one or more clinicaltrials altogether and could delay or prevent our receipt of necessary regulatory approvals. Enrollment delays in our clinical trials may result in increaseddevelopment costs for our product candidates, which would cause the value of our company to decline and limit our ability to obtain additional financing.Our product candidates may cause undesirable side effects, serious adverse events or have other properties that could delay or halt clinical trials, delay orprevent their regulatory approval, limit the commercial profile of their labeling, if approved, or result in significant negative consequences following anymarketing approval.Undesirable side effects or serious adverse events caused by our product candidates could cause us or regulatory authorities to interrupt, delay or haltrespective clinical trials and could result in a restrictive label or the delay or denial of regulatory approval by the FDA or other comparable foreign regulatoryauthorities, including Health Canada or the European Commission.High-risk NMIBC (Vicinium)There were no Grade 4 or Grade 5 serious adverse events that were considered by the clinical investigator to be related to Vicinium during the Phase 1 andPhase 2 clinical trials of Vicinium for the treatment of high-risk NMIBC. There was one Grade 5 serious adverse event, or death, which was determined by theclinical investigator to be unrelated to Vicinium. The most common reported treatment-related adverse events were an abnormally frequent passage of smallamounts of urine, blood in the urine and painful urination, the majority of which were considered to be mild or moderate in severity. No patientsdiscontinued treatment due to a Vicinium-related adverse event during the Phase 1 and Phase 2 clinical trials of Vicinium for the treatment of high-riskNMIBC.In the Phase 3 clinical trial of Vicinium for the treatment of high-risk NMIBC, as of the December 3, 2018 data cut off, there were four treatment-relatedserious adverse events reported in three patients including acute renal injury (Grade 3), pyrexia (Grade 2), cholestatic hepatitis (Grade 4) and renal failure(Grade 5). The most commonly reported treatment-related adverse events were dysuria (13%), hematuria (12%) and urinary tract infection (11%) - all of whichare consistent with the profile of bladder cancer patients and the use of catheterization for treatment delivery. These adverse events were determined to bemanageable and reversible, and only five patients discontinued treatment due to an adverse event.SCCHN (Vicinium)There were no Grade 5 serious adverse events that were considered by the clinical investigator to be related to Vicinium during the Phase 1, Phase 2 or Phase3 clinical trials of Vicinium for the treatment of SCCHN. The Grade 3 and Grade 4 serious adverse events that were reported in the clinical trials of Viciniumfor the treatment of SCCHN and were considered to be possibly, probably or definitely related to treatment consisted of abnormal tumor growth, anorexia,cancer pain, decrease in red blood cells, difficulty swallowing, elevated calcium levels, facial pain, fatigue, high blood sugar, influenza-like illness, injectionsite pain, liver function abnormalities, low albumin level, low sodium concentration, nausea, rash, swelling, tumor hemorrhage and tumor necrosis. Sevenpatients died during the clinical trials of Vicinium for the treatment of SCCHN, but none of the deaths were deemed to be related to Vicinium. Eleven patientsdiscontinued treatment due to liver function test abnormalities; however, the serum levels were transient and they eventually returned to baseline withoutany evidence of permanent liver damage. Four patients withdrew from the clinical trials. Three of the four patients withdrew at their request and one of thefour patients withdrew at the request of the investigator.Multiple types of EpCAM-positive solid tumors (VB6-845d)There were no Grade 5 serious adverse events that were considered by the clinical investigator to be related to VB6-845, which is the prior version of VB6-845d, during the Phase 1 clinical trial. The Grade 3 and Grade 4 serious adverse events that were63Table of Contentsconsidered to be possibly, probably or definitely related to treatment consisted of an infusion related reaction and an infusion site reaction. We have noclinical safety data on human exposure to VB6-845d.As a result of these side effects and serious adverse events or further safety or toxicity issues that we may experience in our clinical trials in the future, we maynot receive regulatory approval for any of our product candidates or we may receive approval subject to a REMS or other post-marketing obligations, whichcould prevent us from ever generating revenues or achieving profitability. Results of our clinical trials could reveal an unacceptably high severity andprevalence of side effects or serious adverse events. As a result, our clinical trials could be suspended or terminated and the FDA or comparable foreignregulatory authorities, including Health Canada, the EMA and the European Commission, could order us to cease further development or deny approval ofany of our product candidates for any or all targeted indications. The related drug-side effects or serious adverse events in our clinical trials could affectclinical trial patient recruitment or the ability of enrolled patients to complete the clinical trial or result in potential product liability claims.We have no clinical safety data on human exposure to VB6-845d or any of our other pre-clinical product candidates. Many compounds that initially showedpromise in clinical or early stage testing for treating cancers have later been found to cause side effects that prevented further development of the compound.Additionally, if our product candidates receive marketing approval, and we or others later identify undesirable side effects or serious adverse events causedby our product candidates, a number of potentially significant negative consequences could result, including:•we may suspend or be forced to suspend marketing of our product candidates;•we may be obliged to conduct a product recall or product withdrawal;•regulatory authorities may suspend, vary, or withdraw their approvals of our product candidates;•regulatory authorities may order the seizure or recall of our product candidates;•regulatory authorities may require additional warnings on the label or a REMS that could diminish the usage or otherwise limit the commercialsuccess of our product candidates;•we may be required to conduct post-marketing studies;•we could be sued and held liable for harm caused to patients;•we could be required to pay fines and face other administrative, civil and criminal penalties; and•our reputation may suffer.Any of these events could prevent us from achieving or maintaining market acceptance of our product candidates, if approved.We identified a potential issue regarding the sensitivity of an assay we employed in our Vicinium clinical trials. The FDA could take a number of actionsin response to this issue, which could have a material adverse effect on our business.In our Phase 3 clinical trials of Vicinium for the treatment of high-risk NMIBC, we have been and are generating pharmacokinetic data. We identified apotential issue regarding the sensitivity of the assay we employed. We used the same assay in the Phase 1 clinical trial for Vicinium. We did not evaluatepharmacokinetics in the Phase 2 clinical trial for Vicinium. We notified the FDA of this issue and are working to develop an appropriate action plan toaddress this issue. We are closely monitoring the patients enrolled in our ongoing Phase 3 clinical trial of Vicinium and we do not believe that patients in thisclinical trial are exposed to any additional material risk due to the issue surrounding the assay. The FDA could take a number of actions in response to thisissue, including requiring us to modify the protocol for our Phase 3 clinical trial, insisting on additional patient monitoring or placing our Phase 3 clinicaltrial on partial or full clinical hold. Any such actions could have a material adverse effect on our business.We will need to obtain FDA approval of any proposed names for our product candidates, and any failure or delay associated with such naming approvalmay adversely impact our business.We have not yet submitted our proposed proprietary name Vicinium, to the FDA or any foreign regulatory authority, including Health Canada or theEuropean Commission, for provisional approval. Any proprietary name we propose to use with our product candidates in the United States must be approvedby the FDA, regardless of whether we have registered it, or applied to register it, as a trademark. The FDA reviews any proposed product name, including anevaluation of potential for confusion with other product names. The FDA may also object to a product name if it believes the name inappropriately impliesmedical64Table of Contentsclaims or contributes to an overstatement of efficacy. If the FDA objects to any proposed proprietary product name, we may be required to expend significantadditional resources in an effort to identify a suitable proprietary product name that would qualify under applicable laws, not infringe the existing rights ofthird parties and be acceptable to the FDA. We may apply for and could possibly obtain provisional approval of our proprietary name by the FDA prior tosubmission of our BLAs. However, this approval is subject to further and final review by the FDA at the time of BLA review.We may attempt to secure approval from the FDA or comparable non-U.S. regulatory authorities through the use of accelerated registration pathways. Ifunable to obtain approval under an accelerated pathway, we may be required to conduct additional pre-clinical studies or clinical trials beyond those thatwe contemplate, which could increase the expense of obtaining, and delay the receipt of, necessary marketing approvals. Even if we receive acceleratedapproval from the FDA, if our confirmatory trials do not verify clinical benefit, or if we do not comply with rigorous post-marketing requirements, the FDAmay seek to withdraw accelerated approval.We may seek an accelerated approval development pathway for certain indications for our product candidates, including Vicinium in BCG refractory high-risk NMIBC. Under the accelerated approval provisions in the FDCA and the FDA’s implementing regulations, the FDA may grant accelerated approval to aproduct designed to treat a serious or life-threatening condition that provides meaningful therapeutic advantage over available therapies and demonstrates aneffect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit. The FDA considers a clinical benefit to bea positive therapeutic effect that is clinically meaningful in the context of a given disease. For the purposes of accelerated approval, a surrogate endpoint is amarker, such as a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit, but is not itself ameasure of clinical benefit. An intermediate clinical endpoint is a clinical endpoint that can be measured earlier than an effect on irreversible morbidity ormortality that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit.If we choose to pursue accelerated approval, we intend to seek feedback from the FDA or will otherwise evaluate our ability to seek and receive suchaccelerated approval. There can be no assurance that the FDA will agree that our proposed primary endpoint of a pivotal study is an appropriate surrogateendpoint. There also can be no assurance that, after our evaluation of the feedback from the FDA or other factors, we will decide to pursue or submit a BLA foraccelerated approval or any other form of expedited development, review or approval. Furthermore, if we submit an application for accelerated approval,there can be no assurance that such application will be accepted or that approval will be granted on a timely basis, or at all. For example, if another companyreceives full approval from the FDA to market a product for treatment of BCG-unresponsive high-risk NMIBC, our ability to seek and obtain acceleratedapproval for Vicinium in the same indication may be materially adversely affected. The FDA or foreign regulatory authorities also could require us toconduct further studies prior to considering our application or granting approval of any type. We might not be able to fulfill the FDA’s requirements in atimely manner, which would cause delays, or approval might not be granted because our submission is deemed incomplete by the FDA. A failure to obtainaccelerated approval or any other form of expedited development, review or approval for a product candidate would result in a longer time period tocommercialize such product candidate, could increase the cost of development of such product candidate and could harm our competitive position in themarketplace.Moreover, even if we receive accelerated approval from the FDA, we will be subject to rigorous post-marketing requirements, including the completion ofconfirmatory post-market clinical trial(s) to verify the clinical benefit of the product, and submission to the FDA of all promotional materials 30-120 daysprior to their dissemination. The FDA could seek to withdraw accelerated approval for multiple reasons, including if we fail to conduct any required post-market study with due diligence, a post-market study does not confirm the predicted clinical benefit, other evidence shows that the product is not safe oreffective under the conditions of use, or we disseminate promotional materials that are found by the FDA to be false and misleading.Failure to successfully validate, develop and obtain regulatory approval for companion diagnostics for our product candidates could impede developmentand commercialization.We have developed a companion diagnostic for use with Vicinium for the treatment of SCCHN. The FDA and comparable foreign regulatory authorities,including Health Canada, will require the development and regulatory approval or CE marking of a companion diagnostic as a condition to approvingVicinium for the treatment of SCCHN. Companion diagnostics developed in conjunction with clinical programs for the associated product candidates aresubject to regulation by the FDA and comparable foreign regulatory authorities, including Health Canada or the competent authorities of the E.U. MemberStates, as medical devices, and require separate approval or the affixing of a CE mark prior to their commercialization. Each regulatory body that approves aproduct candidate will independently need to review and/or approve the companion diagnostic or verify that the product is CE marked before orconcurrently with its approval of the product candidate, and before a product can be commercialized. During a Type C meeting with the FDA in 2007, theFDA noted that approval of a companion diagnostic for EpCAM expression would need to coincide with Vicinium approval for the treatment of SCCHN. Weintend to clarify whether65Table of Contentsthe FDA still believes that a companion diagnostic is necessary to receive approval. The FDA may still require that a companion diagnostic for EpCAMexpression be approved before or at the time of Vicinium's approval for the treatment of SCCHN. We and any potential future third-party collaborators mayencounter difficulties in developing and obtaining approval for or affixing a CE mark to any companion diagnostic. Any delay or failure by us or our futurethird-party collaborators to develop or obtain regulatory approval or CE mark for a companion diagnostic could delay or prevent approval of Vicinium forthe treatment of SCCHN, or limit the commercial opportunity for Vicinium. We may also have difficulty achieving adoption of Vicinium for the treatment ofSCCHN if the companion diagnostic is not commercially available or is restricted in its use by payors or other market forces. We could also incur additionalexpense if the FDA or comparable regulatory authorities, including Health Canada, determine that further studies are required before our companiondiagnostic may be approved or CE marked. Even if approved or CE marked, we may experience delays in developing a sustainable, reproducible and scalablemanufacturing process or transferring that process to commercial partners for production, all of which may prevent us from commercializing our productcandidates on a timely or profitable basis, if at all. Additionally, we or our collaborators may encounter production difficulties that could constrain thesupply of the companion diagnostics, affect the ease of use, affect the price or have difficulties gaining acceptance of the use of the companion diagnostics inthe clinical community. If the companion diagnostic for use with Vicinium for the treatment of SCCHN fails to gain market acceptance, our ability to deriverevenues from sales of Vicinium for the treatment of SCCHN, if approved, could be harmed.Because we plan to produce commercial supply of our product candidate Vicinium for the treatment of high-risk NMIBC, if approved, through a third-party manufacturer, the FDA or foreign regulatory authorities may require us to demonstrate that the product manufactured by our third-partymanufacturer is comparable in quality, safety, and efficacy to the product that was used in our clinical trials. If we experience challenges in demonstratingcomparability, or if the FDA or foreign regulatory authorities require additional nonclinical or clinical studies to demonstrate comparability, theapproval and/or commercialization of Vicinium could be delayed, adversely affected or terminated, or may result in significantly higher costs.Our product candidate, Vicinium for the treatment of high-risk NMIBC, has been produced in our own manufacturing facility for all clinical trials forVicinium to date, including our ongoing Phase 3 clinical trial. In September 2017, we completed the production of all Vicinium necessary for our ongoingPhase 3 clinical trial in our own manufacturing facility. We intend to utilize a third-party manufacturer to produce the commercial supply of Vicinium, ifapproved, and plan to enter into discussions with the FDA and foreign regulatory authorities regarding the criteria for demonstrating comparability ofVicinium produced by our third-party manufacturer to Vicinium produced in our own manufacturing facility. On October 4, 2018, we entered into theFujifilm MSA, pursuant to which Fujifilm will provide certain manufacturing services related to Vicinium. The Fujifilm MSA is designed to facilitate atransfer of certain of our manufacturing processes and technologies from us to Fujifilm to determine if Fujifilm or another CMO can develop the bulk drugsubstance form of Vicinium for commercial purposes if we receive regulatory approval to market Vicinium for the treatment of high-risk NMIBC.Although we do not anticipate changes to the raw materials, formulations or properties nor do we anticipate changes to the Vicinium manufacturing processor finished product specifications as a result of this transfer, because this manufacturing change is being introduced at an advanced stage of development ofVicinium, the FDA and foreign regulatory authorities may require a comprehensive comparability assessment, potentially including additional nonclinicalstudies or clinical trials utilizing Vicinium produced by our third-party manufacturer, and/or a modification of our ongoing Phase 3 clinical trial to includeVicinium produced by our third-party manufacturer. Such requirements could result in lengthy delays and significantly higher costs for the clinicaldevelopment, filing of a BLA, and potential commercialization of Vicinium. If we are unable to demonstrate comparability of Vicinium produced in our ownmanufacturing to Vicinium produced by our third-party manufacturer, we may not be able to obtain approval of a BLA for Vicinium.If we are unable to effectively transfer our manufacturing process to our third-party manufacturer, we may be unable to continue the clinical development ofor seek marketing approval of Vicinium for the treatment of high-risk NMIBC. If we are able to effectively complete the transfer of certain of ourmanufacturing processes and technologies to FujiFilm, the manufacturing facilities used by Fujifilm to manufacture the bulk drug substance form ofVicinium will be subject to inspections by the FDA, and we will depend on Fujifilm’s ability to comply with current Good Manufacturing Practices or otherapplicable regulatory standards. If they cannot successfully manufacture material in compliance with these strict regulatory requirements, we and they willnot be able to secure or maintain regulatory approval for their manufacturing facilities. If the FDA does not approve the manufacturing facilities of Fujifilmwith respect to the manufacture of the materials covered under the Fujifilm MSA, Fujifilm’s ability to produce the bulk drug substance form of Vicinium on acommercial-scale could be delayed which could adversely affect our ability to commercialize Vicinium for the treatment of high-risk NMIBC. We andFujifilm also may be subject to penalties and sanctions from the FDA and other regulatory authorities for any violations of applicable regulatoryrequirements.66Table of ContentsRisks Related to the Commercialization of Our Product CandidatesOur commercial success depends upon attaining significant market acceptance of our product candidates, if approved, among physicians, patients, third-party payors and the medical community.Even if we obtain regulatory approval for our product candidates, our product candidates may not gain market acceptance among physicians, patients, third-party payors or the medical community. The product candidates that we are developing are based on our TFPT platform, which is a new technology andtherapeutic approach. Market participants with significant influence over acceptance of new treatments, such as physicians and third-party payors, may notadopt a product or treatment based on our TFPT platform and technologies, and we may not be able to convince the medical community and third-partypayors to accept and use, or to provide favorable reimbursement for, any product candidates developed by us or any future collaborators. Market acceptanceof our product candidates, if we receive approval, depends on a number of factors, including:•the perceived quality, efficacy and safety of our product candidates;•clinical indications for which our product candidates are approved;•availability of alternative effective treatments for the disease indications of our product candidates are intended to treat and the relativerisks, benefits and costs of those treatments;•acceptance by physicians, major operators of cancer clinics and patients of our product candidates as safe and effective treatments;•the success of our physician education programs;•potential and perceived advantages of our product candidates over alternative treatments;•safety of our product candidates seen in a broader patient group, potentially including their use outside the approved indications shouldphysicians choose to prescribe them for such uses;•prevalence and severity of any side effects;•any new or unexpected results from additional clinical trials or further analysis of clinical data of completed clinical trials by us or ourcompetitors;•product labeling or patient information requirements imposed by the FDA or other foreign regulatory authorities, including Health Canadaand the EMA;•timing of market introduction of our product candidates as well as competitive products;•the pricing of our treatments, particularly in relation to alternative treatments, and willingness and ability of patients to pay for our productcandidates;•availability of coverage and adequate reimbursement and pricing by third-party payors and government authorities;•maintaining compliance with all applicable regulatory requirements;•relative convenience and ease of administration; and•effectiveness of our sales, marketing and distribution efforts and operations.If our product candidates are approved but fail to achieve market acceptance among physicians, patients, third-party payors or the medical community, wemay not be able to generate significant revenues, which would compromise our ability to become profitable.The market opportunities for our product candidates may be limited to those patients who are ineligible for established therapies or for whom priortherapies have failed, and may be small.Cancer therapies are sometimes characterized as first-line, second-line or third-line. When cancer is detected early enough, first-line therapy, usuallychemotherapy, hormone therapy, surgery, radiotherapy or a combination of these, is sometimes adequate to cure the cancer or prolong life without a cure.Second-line and third-line therapies are administered to patients when prior therapy is not effective. We expect to seek initial approval of Vicinium for thetreatment of high-risk NMIBC after prior therapies have failed. Subsequently, for those product candidates that prove to be sufficiently beneficial, if any, wewould expect to seek approval potentially earlier in the treatment paradigm, but there is no guarantee that our product candidates, even if approved, would beapproved for first-line therapy, and, prior to any such approvals, we will have to conduct additional clinical trials.67Table of ContentsOur projections of both the number of people who have the cancers we are targeting, as well as the subset of people with these cancers who have previouslyfailed prior treatments, and who have the potential to benefit from treatment with our product candidates, are based on our beliefs and estimates. Theseestimates have been derived from a variety of sources, including scientific literature, surveys of clinics, patient foundations or market research, and may proveto be incorrect. Further, new studies may change the estimated incidence or prevalence of these cancers and the number of patients may turn out to be lowerthan expected. Additionally, the potentially addressable patient population for Vicinium for the treatment of high-risk NMIBC and our other productcandidates may be limited or may not be amenable to treatment with our product candidates. Even if we receive regulatory approval for Vicinium and ourother product candidates and obtain significant market share, because the potential target populations are small, we may never achieve profitability withoutobtaining regulatory approval for additional indications, including the use of the products as first-line or second-line therapies.Our commercial success could depend upon the continued marketing of another company’s approved product, or the approval of another company’sproduct candidate, that is administered with our product candidates.Some of our future clinical trials and some of the indications for which we are developing our product candidates may involve the use of our productcandidates in combination with other companies’ marketed products or product candidates. These marketed products or product candidates may beadministered in a clinical trial in combination with one or more of our product candidates. In the event that any of these pharmaceutical companies hasunforeseen issues that negatively impacts the clinical development, marketing approval or availability of its product or product candidate or otherwise optsto discontinue clinical development or marketing of its product or product candidate, our ability to complete our applicable clinical trials and/or evaluateclinical results for our product candidate in combination with the other company’s marketed product or product candidate may be negatively impacted. As aresult, this could adversely affect our ability to file for, obtain, or maintain regulatory approval for our product candidate on a timely basis, or at all.If we are unable to establish sales, marketing and distribution capabilities, we may not be successful in commercializing any of our product candidates, ifand when they are approved.We do not have a sales or marketing infrastructure and have no experience in the sale, marketing or distribution of therapeutic products. To achievecommercial success for any product for which we have obtained marketing approval, we will need to establish sales, marketing and distribution capabilities,either ourselves or through collaborations or other arrangements with third parties.There are risks involved with establishing our own sales, marketing and distribution capabilities. For example, recruiting and training a sales force isexpensive and time consuming and could delay any product launch. If the commercial launch of any product candidate for which we recruit a sales force andestablish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercializationexpenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.Factors that may inhibit our efforts to commercialize any product candidates on our own include:•our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;•the inability of sales personnel to obtain access to physicians or persuade adequate numbers of physicians to prescribe our products;•the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companieswith more extensive product lines; and•unforeseen costs and expenses associated with creating an independent sales and marketing organization.We may enter into arrangements with third parties to perform sales, marketing and distribution services in markets outside the United States. We may alsoenter into arrangements with third parties to perform these services in the United States if we do not establish our own sales, marketing and distributioncapabilities in the United States or if we determine that such third-party arrangements are otherwise beneficial. Our product revenues and our profitability, ifany, under any such third-party sales, marketing or distribution arrangements are likely to be lower than if we were to market, sell and distribute any productcandidates ourselves. In addition, we may not be successful in entering into arrangements with third parties to sell, market and distribute any productcandidates or may be unable to do so on terms that are favorable to us. We likely will have little control over such third parties, and any of them may fail todevote the necessary resources and attention to sell and market our product candidates effectively. If we do not establish sales, marketing and distributioncapabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing any product candidates forwhich we may obtain approval.68Table of ContentsWe face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than we do.The development and commercialization of new biologics products is highly competitive. We face competition with respect to our product candidates andwill face competition with respect to any other product candidates that we may seek to develop or commercialize in the future, from both large and smallpharmaceutical, biopharmaceutical and biotechnology companies, academic institutions and other research organizations; and particularly from companies,institutions and organizations that are actively researching, developing, or marketing products that attach proprietary cell-killing payloads to antibodies fortargeted delivery to cancer cells. There are a number of large pharmaceutical, biopharmaceutical and biotechnology companies that currently market and sellproducts or are pursuing the development of products for the treatment of the respective disease indications for which we are developing our productcandidates. We believe that a significant number of products are currently under development, and may become commercially available in the future, for thetreatment of conditions for which we are currently developing, and may try to develop, product candidates. There is intense and rapidly evolvingcompetition in the biotechnology, biopharmaceutical and antibody fragment and immuno-oncology therapeutics fields. Some of these competitive productsand therapies are based on scientific approaches that are similar to our approach, and others are based on entirely different approaches. We are aware ofseveral companies that are developing, or have developed cancer immunotherapies and antibody drug conjugates, or ADCs, and we are also aware of severalcompanies developing product candidates that target the same cancer pathways that we are targeting or that are testing product candidates in the same cancerindications that we are testing. For example, there are several companies that have programs that attach proprietary cell-killing payloads to antibodies fortargeted delivery to cancer cells.In addition to competition from alternative treatments, we eventually may also face competition from products that are biosimilar to, and possiblyinterchangeable with, our product candidates. Even if our product candidates achieve marketing approval, they may be priced at a significant premium overcompetitive biosimilar products, and insurers or other third-party payors may encourage or even require the use of lower priced biosimilar products. Inaddition, we may face significant competition upon expiration of our intellectual property protection.We also face substantial competition with respect to our EBI-031 program. The current standard of care for DME includes anti-VEGF therapies andcorticosteroids. Some patients with DME are effectively treated by the current standard of care therapies. Approved anti-VEGF therapies for treating DMEinclude Lucentis (ranibizumab) and Eylea® (aflibercept). Off-label use of Avastin (bevacizumab) is also seen in DME. Approved corticosteroid therapiesinclude Ozurdex (dexamethasone implant) and Iluvien (fluocinolone implant). Laser photocoagulation was historically the standard of care for treating DME,in particular for a subcategory of DME called clinically significant macular edema, and is still used to treat some DME patients. However, anti-VEGF therapyhas been proven in clinical trials to have superior efficacy over laser photocoagulation.Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have feweror less severe side effects, are more convenient or are less expensive than product candidates that we may develop. Our competitors also may obtain FDA orother regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strongmarket position before we are able to enter the market.In addition, our ability to compete may be affected in many cases by insurers or other third-party payors, particularly Medicare, seeking to encourage the useof generic drug products. Generic products are currently being used as part of the standard of care for the indications that we are pursuing, and additionalproducts are expected to become available on a generic basis over the coming years. If any product candidate that we may develop achieves marketingapproval, we expect that it will be priced at a significant premium over competitive generic products.More established companies may have a competitive advantage over us due to their greater size, cash flow and institutional experience. Compared to us,many of our competitors may have significantly greater financial, technical and human resources. As a result of these factors, our competitors may obtainregulatory approval of their product candidates before we are able to, which may limit our ability to develop or commercialize our product candidates. Ourcompetitors may also develop drugs that are safer, more effective, more widely used and cheaper than ours, and may also be more successful than us inmanufacturing and marketing their products. These appreciable advantages could render our product candidates obsolete or non-competitive before we canrecover the expenses of development and commercialization.If the value framework published by the ASCO to assess the value of cancer treatment options is adopted and utilized by payors and physicians and wewere to receive low ratings, it could adversely affect the price and reimbursement of our products, if approved, reduce prescriptions and harm our business.69Table of ContentsOn May 31, 2016, ASCO published a framework to assess the value of cancer treatment options. The framework was developed in response to concern thatnew, expensive cancer treatments may not be supported by adequate medical evidence. The purpose of the framework is to provide a standardizedquantification of cancer treatments and assist oncologists and patients in deciding between new cancer treatments and the standard of care. The frameworktakes into account a medication’s (i) efficacy, (ii) safety and (iii) cost, to derive an overall treatment value.This framework is described by ASCO as providing a basis for a new software tool that doctors can use to assist shared decision-making with their patients.While we believe that the safety and efficacy profiles of our product candidates are potentially better than that of the standard of care and, if approved, weintend to price our products competitively, we do not know how the data will be assessed by ASCO. It is also unknown whether use of this application couldadversely affect the assessment of any of our product candidates. If this framework and software were adopted and utilized by payors and physicians, and ifour product candidates were to receive low ratings, this could adversely affect the price and reimbursement of our product candidates, if approved, reduceprescriptions and harm our business.Even if we are able to commercialize any product candidate that we may develop, the products may become subject to unfavorable pricing regulations,third-party coverage or reimbursement practices or healthcare reform initiatives, which could harm our business.Our ability to commercialize any product candidates that we may develop successfully will depend, in part, on the extent to which coverage and adequatereimbursement for these products and related treatments will be available from government healthcare programs, private health insurers, managed care plansand other organizations. Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide whichmedications they will pay for and establish reimbursement levels. A primary trend in the U.S. healthcare industry and elsewhere is cost containment.Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particularmedications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and arechallenging the prices charged for medical products. Coverage and reimbursement may not be available for a product that we commercialize and, even if theyare available, the level of reimbursement may not be satisfactory.Inadequate reimbursement may adversely affect the demand for, or the price of, any product candidate for which we obtain marketing approval. Obtainingand maintaining adequate reimbursement for our products may be difficult. We may be required to conduct expensive pharmacoeconomic studies to justifycoverage and reimbursement or the level of reimbursement relative to other therapies. If coverage and adequate reimbursement are not available orreimbursement is available only to limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketingapproval.There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the indicationsfor which the drug is approved by the FDA or similar regulatory authorities outside the United States, including Health Canada, or the European Commission.Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our costs, includingresearch, development, manufacture, sale and distribution expenses. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient tocover our costs and may not be made permanent. Reimbursement rates may vary according to the clinical setting in which a drug is used, may be based onreimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reducedby mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrictimports of drugs from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coveragepolicy and payment limitations in setting their own reimbursement policies. Our inability to promptly obtain coverage and adequate reimbursement ratesfrom both government-funded and private payors for any approved products that we develop would compromise our ability to generate revenues and becomeprofitable.The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products vary widely from country to country. Currentand future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtainingapprovals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins aftermarketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmentalcontrol even after initial approval is granted. As a result, we might obtain marketing approval for a product in a particular country, but then be subject toprice regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues we are able togenerate from the sale of the product in that country. To obtain reimbursement or pricing approval in some countries, we may be required to conduct aclinical trial that compares the cost-effectiveness of our70Table of Contentsproduct candidate to other available therapies. Adverse pricing limitations may hinder our ability to recoup our investment in one or more productcandidates, even if our product candidates obtain marketing approval.There can be no assurance that our product candidates or any products that we may in-license, if they are approved for sale in the United States or in othercountries, will be considered medically reasonable and necessary for a specific indication, that they will be considered cost-effective by third-party payors,that coverage and an adequate level of reimbursement will be available, or that third-party payors’ reimbursement policies will not adversely affect ourability to sell our product candidates profitably. In addition, we are unable to predict what changes in legislation or regulation relating to the health careindustry or third-party coverage and reimbursement may be enacted in the future and how such legislation or regulation could impact our business. See therisk factor entitled “Current and future legislation may increase the difficulty and cost for us and any collaborators to obtain marketing approval of ourproduct candidates and affect the prices we, or they, may obtain” in this Annual Report on Form 10-K for more information, including with respect to theAffordable Care Act.Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we develop.We face an inherent risk of product liability exposure related to the use of any product candidates that we develop in human clinical trials and will face aneven greater risk if we commercially sell any products that we develop. If we cannot successfully defend ourselves against claims that our product candidatesor products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:•decreased demand for any product candidates or products that we develop;•injury to our reputation and significant negative media attention;•withdrawal of clinical trial patients;•significant costs to defend the related litigation;•substantial monetary awards to trial patients;•loss of revenue;•reduced time and attention of our management to pursue our business strategy; and•the inability to commercialize any products that we develop.We currently hold $10.0 million CAD in product liability insurance coverage in the aggregate, with a per incident limit of $10.0 million CAD, which maynot be adequate to cover all liabilities that we may incur. We would need to increase our insurance coverage if we expand our clinical development activitiesbeyond historical levels. We would need to further increase our insurance coverage if we commence commercialization of any product candidate thatreceives marketing approval. Insurance coverage is increasingly expensive. We may not be able to maintain insurance coverage at a reasonable cost or in anamount adequate to satisfy any liability that may arise.We conduct certain elements of our business internationally, and the decisions of sovereign governments could have a material adverse effect on ourbusiness, financial condition and results of operations.Viventia was founded as a Canadian company and conducted its business internationally. In addition to our clinical trials in the United States and Canada,Viventia has historically conducted clinical trials in Russia and Brazil. We intend to, and may, conduct clinical trials in other jurisdictions. Sovereigngovernments, including Canada, may establish laws or regulations that will be deleterious to our interests or that will affect our ability, to obtain access toregulatory agencies in Russia, Brazil, Canada, and/or other jurisdictions. Governments have also, from time to time, established foreign exchange controlswhich could have a material adverse effect on our business, financial condition and results of operations. To date, neither our operations nor our financialcondition have been materially impacted due to laws or regulations of sovereign governments.Risks Related to the License Agreement with RocheWe depend on our license agreement with Roche for the development and commercialization of EBI-031.On June 10, 2016, we entered into the License Agreement with Roche. The License Agreement became effective on August 16, 2016, following stockholderapproval. Under the License Agreement, we granted Roche an exclusive, worldwide license, including the right to sublicense, to our patent rights and know-how related to our monoclonal antibody EBI-031 or any other IL-6 antagonist anti-IL-6 monoclonal antibody, to make, have made, use, have used, register,have registered, sell, have sold,71Table of Contentsoffer for sale, import and export any product containing such an antibody or any companion diagnostic used to predict or monitor response to treatment withsuch a product, or collectively, Licensed Intellectual Property.Pursuant to the terms of the License Agreement, Roche is required to continue developing EBI-031 and any other product made from the LicensedIntellectual Property that contains an IL-6 antagonist anti-IL-6 monoclonal antibody, or Licensed Product, and pursue ongoing patent prosecution, at its cost.Roche paid an up-front license fee of $7.5 million upon effectiveness of the license under the License Agreement, and agreed to pay up to an additional$262.5 million upon the achievement of specified regulatory, development and commercial milestones with respect to up to two unrelated indications.Specifically, an aggregate amount of up to $197.5 million is payable to us for the achievement of specified milestones with respect to the first indication:consisting of $72.5 million in development milestones, $50.0 million in regulatory milestones and $75.0 million in commercialization milestones.The first development milestone payment equaled $22.5 million as a result of the IND application for EBI-031 becoming effective on or before September 15,2016, and which was paid to us in September 2016. Additional amounts of up to $65.0 million are payable upon the achievement of specified developmentand regulatory milestones in a second indication.In addition, we are entitled to receive royalty payments in accordance with a tiered royalty rate scale, with rates ranging from 7.5% to 15% for net sales ofpotential future products containing EBI-031 and up to 50% of these rates for net sales of potential future products containing other IL-6 compounds, witheach of the royalties subject to reduction under certain circumstances and to the buy-out options of Roche further described below.The License Agreement provides for two “option periods” during which Roche may elect to make a one-time payment to us and, in turn, terminate itsdiligence, milestone and royalty payment obligations under the License Agreement. Specifically, (i) Roche may exercise a buy-out option followingInitiation in the first Phase 2 study for a Licensed Product until the day before Initiation of the first Phase 3 study for a Licensed Product, in which case Rocheis required to pay us $135.0 million within 30 days after Roche’s exercise of such buy-out option and receipt of an invoice from us, or (ii) Roche mayexercise a buy-out option following the day after Initiation of the first Phase 3 study for a Licensed Product until the day before the acceptance for review bythe FDA or other regulatory authority of a BLA or similar application for marketing approval for a Licensed Product in either the United States or in the E.U.,in which case Roche is required to pay us, within 30 days after Roche’s exercise of such buy-out option and receipt of an invoice from us, $265.0 million,which amount would be reduced to $220.0 million if none of our patent rights containing a composition of matter claim covering any compound or LicensedProduct has issued in the E.U.The right to potential future payments under the License Agreement represents a significant portion of the value of the License Agreement to us. We cannotbe certain that we will receive any future payments under the License Agreement, which would adversely affect the trading price of our common stock andour business prospects.Additionally, if Roche were to breach or terminate the License Agreement, we may not be able to obtain, or may be delayed in obtaining, marketingapprovals for EBI-031 and will not be able to, or may be delayed in our efforts to, successfully commercialize EBI-031. We may not be able to seek andobtain a viable, alternative collaborator to partner for the development and commercialization of the licensed products on similar terms or at all.The successful commercialization and continued development of EBI-031 depends substantially on the License Agreement with Roche. If Roche is unableor unwilling to commercialize or further develop EBI-031, or experiences significant delays in doing so, our business will be materially harmed.On June 10, 2016, we entered into the License Agreement with Roche for the development and commercialization of EBI-031. Prior to this agreement, we didnot have a history of working with Roche. The License Agreement provides for milestone payments to us based on the achievement of specifieddevelopment, regulatory and commercial milestones, and provides us with royalty-based revenue if EBI-031 is successfully commercialized. We cannotpredict the success of the License Agreement.We are substantially dependent on Roche to develop and commercialize EBI-031. Under the License Agreement, Roche has significant control over theconduct and timing of development and commercialization efforts with respect to EBI-031. We have little control over the amount, timing and quality ofresources that Roche devotes to the development or commercialization of EBI-031. If Roche fails to devote sufficient financial and other resources to thefuture development or commercialization of EBI-031, the development and commercialization of EBI-031 would be delayed or could fail. This would resultin a delay in our receiving milestone payments or royalties at all.72Table of ContentsRisks Related to Our Dependence on Third PartiesWe may enter into collaborations or license agreements with third parties for the development or commercialization of our product candidates. If ourcollaborations or licenses are not successful, we may not be able to capitalize on the market potential of these product candidates.We may seek third-party collaborators or licensees for development and commercialization of our product candidates. Our likely collaborators or licenseesfor any sales, marketing, distribution, development, licensing or broader collaboration arrangements include large and mid-size pharmaceutical companies,regional and national pharmaceutical companies and biotechnology companies. We are not currently party to any such arrangement, other than the LicenseAgreement with Roche. Our ability to generate revenues from these arrangements will depend on our collaborators’ or licensee's abilities and efforts tosuccessfully perform the functions assigned to them in these arrangements.Collaborations and licenses involving our product candidates, including the License Agreement with Roche, pose a number of risks, including the following:•collaborators or licensees have significant discretion in determining the amount and timing of efforts and resources that they will apply tothese collaborations or licenses;•collaborators or licensees may not perform their obligations as expected;•collaborators or licensees may not pursue development and commercialization of our product candidates that receive marketing approval ormay elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’or licensees' strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competingpriorities;•collaborators or licensees may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon aproduct candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing;•collaborators or licensees could independently develop, or develop with third parties, products that compete directly or indirectly with ourproducts or product candidates if the collaborators or licensees believe that competitive products are more likely to be successfullydeveloped or can be commercialized under terms that are more economically attractive than ours;•product candidates discovered under the collaboration or license with us may be viewed by our collaborators or licensees as competitivewith their own product candidates or products, which may cause collaborators or licensees to cease to devote resources to thecommercialization of our product candidates;•a collaborator or licensee with marketing and distribution rights to one or more of our product candidates that achieve regulatory approvalmay not commit sufficient resources to the marketing and distribution of such product or products;•disagreements with collaborators or licensees, including disagreements over proprietary rights, contract interpretation or the preferredcourse of development, might cause delays or termination of the research, development or commercialization of product candidates, mightlead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which woulddivert management attention and resources, be time-consuming and expensive;•collaborators or licensees may not properly maintain or defend our intellectual property rights or may use our proprietary information insuch a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us topotential litigation;•collaborators or licensees may infringe the intellectual property rights of third parties, which may expose us to litigation and potentialliability; and•collaborations or licenses may be terminated for the convenience of the collaborator or licensee and, if terminated, we could be required toraise additional capital to pursue further development or commercialization of the applicable product candidates.Collaboration agreements and licenses may not lead to development or commercialization of product candidates in the most efficient manner, or at all. If anycollaborations or licenses that we enter into, do not result in the successful development and commercialization of products or if one of our collaborators orlicensees terminates its agreement with us, we may not receive any future research funding or milestone or royalty payments under the collaboration orlicense. All of the risks relating to73Table of Contentsproduct development, regulatory approval and commercialization described in this Annual Report on Form 10-K would also apply to the activities of anycollaborators and licensees.Additionally, subject to its contractual obligations to us, if a collaborator or licensee of ours were to be involved in a business combination, it mightdeemphasize or terminate the development or commercialization of any product candidate licensed to it by us. If one of our collaborators or licenseesterminates its agreement with us, we may find it more difficult to attract new collaborators or licensees and our perception in the business and financialcommunities could be harmed.If we are not able to establish additional collaborations, we may have to alter our development and commercialization plans and our business could beadversely affected.For some of our product candidates, we may decide to collaborate with pharmaceutical or biotechnology companies for the development and potentialcommercialization of such product candidates. We face significant competition in seeking appropriate collaborators. Whether we reach a definitivecollaboration agreement will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of theproposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials,the likelihood of approval by the FDA or similar regulatory authorities outside the United States, including Health Canada, or the European Commission, thepotential market for the subject product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, thepotential of competing products, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to suchownership without regard to the merits of the challenge, and industry and market conditions generally. The collaborator may also consider alternativeproduct candidates or technologies for similar indications that may be available to collaborate on and whether such a collaboration could be more attractivethan the one with us for our product candidate. We may also be restricted under future license agreements from entering into agreements on certain terms withpotential collaborators. Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a significant number ofrecent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators.If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may have to curtail the development of aproduct candidate, reduce or delay its development program or one or more of our other development programs, delay its potential commercialization orreduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our ownexpense. If we elect to fund and undertake development or commercialization activities on our own, we may need to obtain additional expertise andadditional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into collaborations and do not have sufficient funds orexpertise to undertake the necessary development and commercialization activities, we may not be able to further develop our product candidates or bringthem to market or continue to develop our product platform.We rely on third parties to conduct our pre-clinical studies and clinical trials. If these third parties do not successfully carry out their contractual duties ormeet expected deadlines, we may not be able to obtain regulatory approval for or commercialize our product candidates.We rely on domestic and international third-party CROs to monitor and manage data for our ongoing pre-clinical and clinical programs. We rely on theseparties for execution of our pre-clinical studies and clinical trials, and we control only some aspects of their activities. Nevertheless, we are responsible forensuring that each of our pre-clinical studies and clinical trials is conducted in accordance with the applicable protocol and legal, regulatory and scientificstandards, and our reliance on the CROs does not relieve us of our regulatory responsibilities. We also rely on third parties to assist in conducting our pre-clinical studies in accordance with GLP and the Animal Welfare Act requirements. We and our CROs are required to comply with U.S. federal regulations andcurrent GCP, which are international standards meant to protect the rights and health of patients and assure the credibility of clinical trial data that areenforced by the FDA, Health Canada, the competent authorities of the E.U. Member States and comparable foreign regulatory authorities for all of ourproduct candidates in clinical development. Regulatory authorities enforce GCP through periodic inspections of trial sponsors, principal investigators andtrial sites. If we or any of our CROs fail to comply with applicable GCP, the clinical data generated in our clinical trials may be deemed unreliable and theFDA or comparable foreign regulatory authorities, including Health Canada and the EMA, may require us to perform additional clinical trials beforeapproving our marketing applications. We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will determinethat any of our clinical trials comply with GCP requirements. In addition, our clinical trials must be conducted with product produced under cGMPrequirements. Failure to comply with these regulations may require us to repeat pre-clinical studies and clinical trials, which would delay the regulatoryapproval process.74Table of ContentsOur CROs are not our employees, and except for remedies available to us under our agreements with such CROs, we cannot control whether or not theydevote sufficient time and resources to our ongoing clinical, non-clinical and pre-clinical programs. If CROs do not successfully carry out their contractualduties or obligations or meet expected deadlines or if the quality or accuracy of the data they obtain is compromised due to the failure to adhere to ourprotocols, regulatory requirements or for other reasons, our pre-clinical studies and clinical trials may be extended, delayed or terminated and we may not beable to obtain regulatory approval for or successfully commercialize our product candidates. As a result, our results of operations and the commercialprospects for our product candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed.Because we have relied and will continue to rely on third parties, our internal capacity to perform these functions is limited. Outsourcing these functionsinvolves risk that third parties may not perform to our standards, may not produce results in a timely manner or may fail to perform at all. In addition, the useof third-party service providers requires us to disclose our proprietary information to these parties, which could increase the risk that this information will bemisappropriated. We currently have a small number of employees, which limits the internal resources we have available to identify and monitor our third-party providers. To the extent we are unable to identify and successfully manage the performance of third-party service providers in the future, our businessmay be adversely affected. Though we carefully manage our relationships with our CROs, there can be no assurance that we will not encounter challenges ordelays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.If we lose our relationships with CROs, our product development efforts could be delayed.We rely on domestic and international third-party vendors and CROs for pre-clinical studies and clinical trials related to our product development efforts.Switching or adding additional CROs would involve additional cost and requires management time and focus. Our CROs generally have the right toterminate their agreements with us in the event of an uncured material breach. In addition, some of our CROs have an ability to terminate their respectiveagreements and/or research projects with us pursuant to such agreements if it can be reasonably demonstrated that the safety of the patients participating inour clinical trials warrants such termination in accordance with the reasonable opinion of the relevant CRO. Identifying, qualifying and managingperformance of third-party service providers can be difficult, time consuming and cause delays in our development programs. In addition, there is a naturaltransition period when a new CRO commences work and the new CRO may not provide the same type or level of services as the original provider. If any ofour relationships with our third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs or to do so on commerciallyreasonable terms.Our experience manufacturing our product candidates is limited to our pre-clinical studies and clinical trials. We have no experience manufacturing ourproduct candidates on a commercial scale. We are dependent on third parties for our supply chain, and if we experience problems with any such thirdparties, the manufacturing of our product candidates could be delayed.We maintain an approximately 31,100 square foot manufacturing, laboratory, warehouse and office facility in Winnipeg, Manitoba, Canada. We have three15 liter fermentors, one 150 liter fermentor, one 500 liter fermentor and one 1,500 liter fermentor. Our classified fermentation suite and post-productionprocessing capabilities are currently dedicated to producing our pre-clinical study and clinical trial batches. In September 2017, we completed themanufacturing of all Vicinium necessary for our ongoing Phase 3 clinical trial in patients with NMIBC, and for our CRADA with the NCI. As a result, we haveended production of Vicinium in our own manufacturing facility and we are redirecting resources toward completing our Phase 3 trial.Our manufacturing facility has been audited by a third party for compliance with cGMP. The most recent audit was in January 2014 and it did not identifyany major impediments to the cGMP manufacturing of product candidates up to and including Phase 3 production. Manufacturing of drugs and productcandidates, including Vicinium and VB6-845d, must comply with cGMP standards and other regulations. Methods of manufacture as well as validation ofmanufacturing procedures and quality control systems are reviewed by regulatory authorities, such as the FDA, Health Canada and the competent authoritiesof the E.U. Member States, to determine their effect on the quality, purity and potency of product candidates. All such manufacturing procedures, validationprograms and quality assessment activities must be properly documented in accordance with regulatory requirements. The FDA, Health Canada and thecompetent authorities of the E.U. Member States conduct inspections to determine compliance with cGMP to ensure that product candidates used in humantesting are adequately characterized in terms of identity, potency and purity. In general, the cGMP standards expected for marketed drugs also apply to thesupply of product candidates evaluated in most stages of clinical testing.In the event we obtain approval from the FDA to market any of our product candidates, we intend to outsource our commercial scale manufacturing to CMOs.We do not have experience in manufacturing products at commercial scale. Additionally, the facilities used by any CMO to manufacture any of our productcandidates must be the subject of a satisfactory inspection before75Table of Contentsthe FDA and other applicable regulatory authorities approve a BLA or marketing authorization for each of our product candidates manufactured at thatfacility. We will depend on these third-party manufacturing partners for compliance with the E.U.’s, FDA’s and comparable foreign regulatory authorities’,including Health Canada’s, requirements for the manufacture of our finished products, if and when our product candidates are approved.Any significant disruption in our supplier relationships could harm our business. Any significant delay in the supply of a product candidate or its keymaterials for an ongoing pre-clinical study or clinical trial could considerably delay completion of such pre-clinical study or clinical trial, product testingand potential regulatory approval of a product candidate. If our CMOs or we are unable to purchase these key materials after regulatory approval has beenobtained for a product candidate, the commercial launch of such product candidate would be delayed or there would be a shortage in supply, which wouldimpair our ability to generate revenues from the sale of such product candidate.In the event that manufacturing process changes are necessary for the further development of a product candidate, we may not be able to reach agreementwith regulatory agencies on the criteria for demonstrating comparability to the original product, which would require us to repeat clinical trials performedwith the original product. This could result in lengthy delays in implementing the new process or site and substantial lost sales as a result of our inability tomeet commercial demand. If we reach agreement with regulatory agencies on the criteria for establishing comparability, we may not be able to meet thesecriteria or may suffer lengthy delays in meeting these criteria. This may result in significant lost sales due to inability to meet commercial demand with theoriginal product. Furthermore, studies to demonstrate comparability, or any other studies on the new process or site such as validation studies, may uncoverfindings that result in regulatory agencies delaying or refusing to approve the new process or site.If we encounter difficulties in identifying and/or negotiating a commercial manufacturing agreement with a third party manufacturer of our productcandidates, or if we experience problems with the third-party manufacturer, the manufacturing of our product candidates and our product developmentand commercialization efforts may be delayed, we may not be able to obtain regulatory approval of our product candidates, and our costs may be higherthan expected, all of which could have a material adverse effect on our business.We intend to rely upon a third-party manufacturer for the commercial supply of our product candidates. Our reliance on a third-party manufacturer willexpose us to certain risks that we would not be subject to if we manufactured those products ourselves, including:•The development of commercial-scale manufacturing capabilities may require our third-party manufacturer to invest substantial additional fundsand hire and retain technical personnel who have the necessary manufacturing experience. Our third-party manufacturer may fail to devote sufficienttime and resources to develop the capabilities to manufacture our product candidates.•Because of the complex nature of our product candidates, our third party manufacturer, or other third parties we rely on, may encounter difficulties inachieving the volume of production needed to satisfy commercial demand, may not be able to achieve such volume at an acceptable cost, mayexperience technical issues that impact comparability, quality, or compliance with applicable regulations governing the manufacture of biologicalproducts, and may experience shortages of qualified personnel to adequately staff production operations.•Our third-party manufacturer could default on its agreement with us to meet our requirements for commercialization of our product candidates, or itmay terminate or decide not to renew its agreement with us, based on its own business priorities, at a time that is costly or damaging to us. If ourthird-party manufacturer were to terminate our arrangement or fail to meet our commercial manufacturing demands, we may be delayed in our abilityto obtain and maintain regulatory approval of our product candidates or, if approved, commercialize our product candidates.•It may be difficult or impossible for us to find a replacement manufacturer on acceptable terms quickly, or at all. Identifying alternate manufacturersmay be difficult because the number of potential manufacturers that have the necessary expertise to produce biologics is limited. Additionally, theFDA must approve any alternative manufacturer before we may use the alternative manufacturer to produce commercial supply of a productcandidate, if approved.Our reliance on a third party manufacturer reduces our control over our commercialization activities but does not relieve us of our responsibility to ensurecompliance with applicable legal and regulatory standards. The FDA and other foreign regulatory authorities require that our product candidates and anyproducts that we may eventually commercialize be manufactured according to cGMP and similar foreign standards. Any failure by our third-partymanufacturer to comply with cGMP or to scale up manufacturing processes, including any failure to deliver sufficient quantities of product candidates in atimely manner, could lead to a delay in, or failure to obtain, regulatory approval of any of our product candidates. In addition, such failure could be the basisfor the FDA or any other foreign regulatory authorities including Health Canada, the European Commission76Table of Contentsor the competent authorities of the E.U. Member States to issue a warning or untitled letter, withdraw approvals for product candidates previously granted tous, or take other regulatory or legal action, including recall or seizure, total or partial suspension of production, suspension of ongoing clinical trials, refusalto approve pending applications or supplemental applications, detention of product, refusal to permit the import or export of products, injunction, imposingadministrative or civil penalties, or pursuing criminal prosecution.Any contamination in our manufacturing process, shortages of raw materials or failure of any of our key suppliers to deliver necessary components of ourTFPT platform could result in delays in our timing for clinical development or obtaining marketing approval.Given the nature of biologics manufacturing, there is a risk of contamination. Any contamination could materially adversely affect our ability to produce ourproduct candidates on schedule and could therefore halt or delay our clinical development programs.Some of the raw materials required in our manufacturing process are derived from biological sources. Such raw materials are difficult to procure and may alsobe subject to contamination or recall. A material shortage, contamination, recall, or restriction on the use of biologically derived substances in themanufacture of our product candidates could halt or delay our clinical development programs or disrupt the commercial manufacturing of our productcandidates, if approved, which could materially and adversely affect our business.Risks Related to Our Intellectual PropertyIf we are unable to obtain and maintain patent protection for our technology and products, or if our licensors are unable to obtain and maintain patentprotection for the technology or products that we license from them, or if the scope of the patent protection obtained is not sufficiently broad, ourcompetitors could develop and commercialize technology and products similar or identical to ours, and our ability to successfully commercialize ourtechnology and products may be impaired.Our success depends in large part on our and our licensors’ ability to obtain and maintain patent protection in the United States and other countries withrespect to our proprietary technology and products. We and our licensors have sought to protect our proprietary position by filing patent applications in theUnited States and abroad related to our novel technologies and product candidates. The patent prosecution process is expensive and time-consuming, and wemay not be able to file and prosecute all necessary or desirable patent applications in jurisdictions of interest at a reasonable cost or in a timely manner. It isalso possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection.Moreover, in some circumstances, we do not have the right to control the preparation, filing and prosecution of patent applications, or to maintain thepatents, covering technology that we license from third parties. Therefore, these patents and applications may not be prosecuted and enforced in a mannerconsistent with the best interests of our business. If such licensors fail to maintain such patents, or lose rights to those patents, the rights we have licensed maybe reduced or eliminated.The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has inrecent years been the subject of much litigation. As a result, the issuance, scope, validity, enforceability and commercial value of our and our licensors’patent rights are highly uncertain. Our and our licensors’ pending and future patent applications may not result in patents being issued which protect ourtechnology or products or which effectively prevent others from commercializing competitive technologies and products. In addition, the laws of foreigncountries may not protect our rights to the same extent as the laws of the United States. For example, European patent law restricts the patentability ofmethods of treatment of the human body more than United States law does. Publications of discoveries in the scientific literature often lag behind the actualdiscoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases notat all. Therefore, we cannot know with certainty whether we or our licensors were the first to make the inventions claimed in our owned or licensed patents orpending patent applications, or that we or our licensors were the first to file for patent protection of such inventions. As a result, the issuance, scope, validity,enforceability and commercial value of our owned or licensed patent rights are highly uncertain. Our pending and future patent applications may not result inpatents being issued which protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitivetechnologies and products. In particular, during prosecution of any patent application, the issuance of any patents based on the application may depend uponour ability to generate additional pre-clinical or clinical data that support the patentability of our proposed claims. We may not be able to generate sufficientadditional data on a timely basis, or at all. Moreover, changes in either the patent laws or interpretation of the patent laws in the United States and othercountries may diminish the value of our patents or narrow the scope of our patent protection.77Table of ContentsRecent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement ordefense of our issued patents. On September 16, 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law. The Leahy-SmithAct includes a number of significant changes to United States patent law. These include provisions that affect the way patent applications are prosecuted andmay also affect patent litigation. The United States Patent Office recently developed new regulations and procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with the Leahy-Smith Act, and in particular, the first to file provisions, only becameeffective on March 16, 2013. Accordingly, it is not clear what, if any, impact the Leahy-Smith Act will have on the operation of our business. However, theLeahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and theenforcement or defense of our issued patents.Moreover, we may be subject to a third-party preissuance submission of prior art to the U.S. Patent and Trademark Office, or USPTO, or become involved inopposition, derivation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights ofothers. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow thirdparties to commercialize our technology or products and compete directly with us, without payment to us, or result in our inability to manufacture orcommercialize products without infringing third-party patent rights. In addition, if the breadth or strength of protection provided by our patents and patentapplications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.In addition, invalidation of our patent rights by third parties could jeopardize the anticipated revenue streams from current licensees.Even if our owned and licensed patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, preventcompetitors from competing with us or otherwise provide us with any competitive advantage. Our competitors may be able to circumvent our owned orlicensed patents by developing similar or alternative technologies or products in a non-infringing manner.The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged inthe courts or patent offices in the United States and abroad. Such challenges may result in loss of exclusivity or freedom to operate or in patent claims beingnarrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar oridentical technology and products, or limit the duration of the patent protection of our technology and products. Given the amount of time required for thedevelopment, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after suchcandidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others fromcommercializing products similar or identical to ours.We may not be able to protect our intellectual property rights throughout the world.Filing, prosecuting and defending patents on all of our product candidates and technologies throughout the world would be prohibitively expensive, and ouror our licensors’ intellectual property rights in some countries outside the United States can be less extensive than those in the United States. In addition, thelaws and practices of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States.Moreover, the intellectual property laws of the United States change over time. For example, several U.S. Supreme Court cases have redefined what isconsidered to be patentable subject matter. Consequently, we and our licensors may not be able to prevent third parties from practicing our and our licensors’inventions in all countries inside or outside the United States, or from selling or importing products made using our and our licensors’ inventions in and intothe United States or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop theirown products, and may export infringing products to territories where we or our licensors have patent protection, but where enforcement is not as strong as inthe United States. These products may compete with our products in jurisdictions where we do not have any issued patents and our patent claims or otherintellectual property rights may not be effective or sufficient to prevent them from so competing.Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legalsystems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection,particularly those relating to biopharmaceuticals, which could make it difficult for us to stop the infringement of our or our licensor’s patents or marketing ofcompeting products in violation of our proprietary rights generally in those countries. Proceedings to enforce our patent rights in foreign jurisdictions couldresult in substantial cost and divert our efforts and attention from other aspects of our business, could put our and our licensors’ patents at risk of beinginvalidated or being interpreted narrowly and put our and our licensors’ patent applications at risk of not issuing and could provoke third parties to assertclaims against us or our licensors. We or our licensors may not prevail in any78Table of Contentslawsuits that we or our licensors initiate and the damages or other remedies awarded, if any, may not be commercially meaningful.The laws of certain foreign countries may not protect our rights to the same extent as the laws of the United States, and these foreign laws may also be subjectto change. For example, methods of treatment and manufacturing processes may not be patentable in certain jurisdictions, and the requirements forpatentability may differ in certain countries, particularly developing countries. Furthermore, generic and/or biosimilar product manufacturers or othercompetitors may challenge the scope, validity or enforceability of our or our licensors’ patents, requiring us or our licensors to engage in complex, lengthyand costly litigation or other proceedings.Generic or biosimilar product manufacturers may develop, seek approval for, and launch biosimilar versions or generic versions, respectively, of our products.The FDA published draft guidance documents on biosimilar product development. If a biosimilar product is also found to be interchangeable with a referenceproduct, it may be substituted for the reference product. Complexities associated with the larger, and often more complex, structures of biological products, aswell as the process by which such products are manufactured, pose significant hurdles to implementation, which are still being worked out by the FDA. If anyof our product candidates are approved by the FDA, the approval of a biologic product biosimilar to or interchangeable with one of our products could have amaterial impact on our business. In particular, a biosimilar could be significantly less costly to bring to market and priced significantly lower than ourproducts, if approved by the FDA.Many countries, including E.U. countries, have compulsory licensing laws under which a patent owner may be compelled under certain circumstances togrant licenses to third parties. In those countries, we and our licensors may have limited remedies if patents are infringed or if we or our licensors arecompelled to grant a license to a third party, whichcould materially diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our and our licensors’ efforts toenforce intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that weown or license.We have not yet registered our trademarks in all of our potential markets, and failure to secure those registrations could adversely affect our business.Our future trademark applications may not be allowed for registration, and our registered trademarks may not be maintained or enforced. During trademarkregistration proceedings, we may receive rejections from the USPTO or other applicable foreign intellectual property offices. Although we are given anopportunity to respond to those rejections, we may be unable to overcome such rejections, or have to expend additional resources to secure registrations,such as commencing cancellation proceedings against third-party trademark registrations to remove them as obstacles to our trademark applications. Inaddition, in the USPTO and in comparable agencies in many foreign jurisdictions, third parties are given an opportunity to oppose pending trademarkapplications and to seek to cancel registered trademarks. Opposition or cancellation proceedings may be filed against our trademarks, and our trademarksmay not survive such proceedings. If we do not secure registrations for our trademarks, we may encounter more difficulty in enforcing them against thirdparties than we otherwise would.We depend on our license agreements with the University of Zurich, Micromet, XOMA and Merck KGaA and if we cannot meet the requirements under theagreements we could lose important rights to Vicinium for the treatment of high-risk NMIBC, Vicinium for the treatment of SCCHN or VB6-845d, whichcould have material adverse effect on our business.We have an exclusive license agreement with Zurich. Pursuant to the agreement, we were granted an exclusive license, with the right to sublicense, undercertain patents primarily relating, in part, to our targeting agents, EpCAM chimera and immunoconjugates (including aspects of Vicinium for the treatment ofhigh-risk NMIBC and Vicinium for the treatment of SCCHN) and methods of use, to make, use, sell and import products that would otherwise infringe suchpatents in the field of the treatment, stasis and palliation of disease in humans. If we fail to meet our obligations under the license agreement, Zurich mayhave the right to terminate our license, and upon the effective date of such termination, our right to use the licensed Zurich patent rights would end. To theextent such licensed technology or patent rights relate to our product candidates, we would expect to exercise all rights and remedies available to us,including attempting to cure any breach by us, and otherwise seek to preserve our rights under the patent rights licensed to us, but we may not be able to doso in a timely manner, at an acceptable cost to us or at all. Any uncured, material breach under the license agreement could result in our loss of rights topractice the patent rights licensed to us under the license agreement, and to the extent such patent rights and other technology relate to our productcandidates or other of our compounds, it could have a material adverse effect on our commercialization efforts for our product candidates, includingVicinium for the treatment of high-risk NMIBC and Vicinium for the treatment of SCCHN.We also have a license agreement with Micromet, which grants us non-exclusive rights, with certain sublicense rights, for know-how and patents allowingexploitation of certain single chain antibody products. If we fail to meet our obligations under79Table of Contentsthe license agreement, Micromet may have the right to terminate our license, and upon the effective date of such termination, our right to use the licensedMicromet patent rights would end. To the extent such licensed technology or patent rights relate to our product candidates, we would expect to exercise allrights and remedies available to us, including attempting to cure any breach by us, and otherwise seek to preserve our rights under the patent rights licensedto us, but we may not be able to do so in a timely manner, at an acceptable cost to us or at all. Any uncured, material breach under the license agreementcould result in our loss of rights to practice the patent rights licensed to us under the license agreement, and to the extent such patent rights and othertechnology relate to our product candidates or other of our compounds, it could have a material adverse effect on our commercialization efforts for ourproduct candidates, including Vicinium for the treatment of high-risk NMIBC and Vicinium for the treatment of SCCHN.We also have a license agreement with XOMA, which grants us non-exclusive rights to certain XOMA patent rights and know-how related to certainexpression technology, including plasmids, expression strains, plasmid maps and production systems. If we fail to meet our obligations under the licenseagreement, XOMA may have the right to terminate our license, and upon the effective date of such termination, our right to use the licensed XOMA patentrights and related know-how would end. To the extent such licensed technology or patent rights relate to our product candidates, we would expect to exerciseall rights and remedies available to us, including attempting to cure any breach by us, and otherwise seek to preserve our rights under the patent rightslicensed to us, but we may not be able to do so in a timely manner, at an acceptable cost to us or at all. Any uncured, material breach under the licenseagreement could result in our loss of rights to practice the patent rights licensed to us under the license agreement, and to the extent such patent rights andother technology relate to our product candidates or other of our compounds, it could have a material adverse effect on our commercialization efforts for ourproduct candidates, including Vicinium for the treatment of high-risk NMIBC and Vicinium for the treatment of SCCHN.We also have a license agreement with Merck, which grants us an exclusive license, with the right to sublicense, under certain patents and technologyrelating to the de-immunization of our cytotoxin Bouganin for therapeutic and in vivo diagnostic purposes in humans. If we fail to meet our obligationsunder this license agreement, Merck may have the right to terminate our license, and upon the effective date of such termination, our right to use the licensedMerck patent rights and technology would end. To the extent such licensed technology or patent rights relate to our product candidates, we would expect toexercise all rights and remedies available to us, including attempting to cure any breach by us, and otherwise seek to preserve our rights under the patentrights and technology licensed to us, but we may not be able to do so in a timely manner, at an acceptable cost to us or at all. Any uncured, material breachunder the license agreement could result in our loss of rights to practice the patent and technology rights licensed to us under the license agreement, and tothe extent such patent rights and other technology relate to our product candidates, it could have a material adverse effect on our commercialization effortsfor product candidates.We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be expensive, time consuming andunsuccessful.Competitors may infringe our issued patents or other intellectual property. To counter infringement or unauthorized use, we may be required to fileinfringement claims, which can be expensive and time consuming. Any claims we assert against perceived infringers could provoke these parties to assertcounterclaims against us alleging that we infringe their patents, trademarks or other intellectual property. In addition, in a patent infringement proceeding, acourt may decide that a patent of ours is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop the other partyfrom using the technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in any litigation proceedingcould put one or more of our patents at risk of being invalidated or interpreted narrowly. In a trademark infringement proceeding, we could be enjoined fromcontinued use of a trademark deemed to be infringing and forced to rebrand product packaging, product inserts, market and advertising materials, resulting ina loss of sales and established goodwill in that name or mark. In addition, we could be found liable for monetary damages, including treble damages andattorneys’ fees if we are found to have willfully infringed a trademark. Furthermore, because of the substantial amount of discovery required in connectionwith intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type oflitigation.Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain andcould have a material adverse effect on the success of our business.Our commercial success depends upon our ability, and the ability of our collaborators, to develop, manufacture, market and sell our product candidates anduse our proprietary technologies without infringing the proprietary rights of third parties. There is considerable intellectual property litigation in thebiotechnology and pharmaceutical industries. We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectualproperty rights with respect to our products and technology, including interference or derivation proceedings before the USPTO. The risks of being involvedin such litigation and proceedings may increase as our product candidates near commercialization and as we gain the greater visibility80Table of Contentsassociated with being a public company. Third parties may assert infringement claims against us based on existing patents or patents that may be granted inthe future. We may not be aware of all such intellectual property rights potentially relating to our product candidates and their uses. Thus, we do not knowwith certainty that any product candidate, or our commercialization thereof, does not and will not infringe or otherwise violate any third party’s intellectualproperty.If we are found to infringe a third party’s intellectual property rights, we could be required to obtain a license from such third party to continue developingand marketing our products and technology. However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even ifwe were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could beforced, including by court order, to cease commercializing the infringing technology or product. In addition, we could be found liable for monetary damages,including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. A finding of infringement could prevent us fromcommercializing our product candidates or force us to cease some of our business operations. Claims that we have misappropriated the confidentialinformation or trade secrets of third parties could have a similar negative impact on our business.If we fail to comply with our obligations in our intellectual property licenses and funding arrangements with third parties, we could lose rights that areimportant to our business.We are party to a number of license agreements and a collaboration agreement that impose, and, for a variety of purposes, we will likely enter into additionallicensing and funding arrangements with third parties that may impose, diligence, development and commercialization timelines and milestone payment,royalty, insurance and other obligations on us. Under certain of our existing licensing agreements, we are obligated to pay royalties or make specifiedmilestone payments on net product sales of product candidates or related technologies to the extent they are covered by the agreement. We also are obligatedunder certain of our existing license agreements to pay maintenance and other fees. We also have diligence and development obligations under certain ofthose agreements that we are required to satisfy. If we fail to comply with our obligations under current or future license and collaboration agreements, ourcounterparties may have the right to terminate these agreements, in which event we might not be able to develop, manufacture or market any product that iscovered by these agreements or may face other penalties under the agreements. Such an occurrence could diminish the value of the product candidate beingdeveloped under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements may result in ourhaving to negotiate new or reinstated agreements with less favorable terms, or cause us to lose our rights under these agreements, including our rights toimportant intellectual property or technology.We may be subject to claims by third parties asserting that our employees, consultants, independent contractors or we have misappropriated theirintellectual property, or claiming ownership of what we regard as our own intellectual property.Many of our employees and our licensors’ employees, including our senior management, were previously employed at universities, medical institutions orother biotechnology or pharmaceutical companies, including our competitors or potential competitors. Some of these employees, including members of oursenior management, executed proprietary rights, non-disclosure and non-competition agreements, or similar agreements, in connection with such previousemployment. Although we try to ensure that our employees do not use the proprietary information or know-how of others in their work for us, we may besubject to claims that these employees or we have used or disclosed intellectual property, including trade secrets or other proprietary information, of any suchemployee’s former employer. Litigation may be necessary to defend against these claims.In addition, while it is our policy to require our employees and contractors who may be involved in the development of intellectual property to executeagreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact developsintellectual property that we regard as our own. Our and their assignment agreements may not be self-executing or may be breached, and we may be forced tobring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property.If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights orpersonnel. Even if we are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction tomanagement.Intellectual property litigation could cause us to spend substantial resources and distract our personnel from their normal responsibilities.Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses, andcould distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results ofhearings, motions or other interim proceedings or developments and if81Table of Contentssecurities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Suchlitigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales,marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some ofour competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources.Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could compromise our ability to compete in themarketplace.If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.In addition to seeking patents for some of our technology and product candidates, we also rely on trade secrets, including unpatented know-how, technologyand other proprietary information, to maintain our competitive position. We seek to protect these trade secrets, in part, by entering into non-disclosure andconfidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, contractmanufacturers, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with ouremployees and consultants. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including ourtrade secrets, and we may not be able to obtain adequate remedies for such breaches. Enforcing a claim that a party illegally disclosed or misappropriated atrade secret is difficult, expensive and time-consuming, and the outcome is unpredictable. In addition, some courts inside and outside the United States areless willing or unwilling to protect trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, wewould have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with us. If any of ourtrade secrets were to be disclosed to or independently developed by a competitor, our competitive position would be harmed.Intellectual property rights do not necessarily address all potential threats to our competitive advantage.The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and may notadequately protect our business, or permit us to maintain our competitive advantage. The following examples are illustrative:•others may be able to make product candidates that are the same as or similar to our product candidates but that are not covered by the claims of thepatents that we own or have licensed;•biosimilar product manufacturers may develop, seek approval for, and launch biosimilar versions of our products, which could be significantly lesscostly to bring to market and priced significantly lower than our products;•we or our licensors might not have been the first inventor to file patent applications covering certain of our inventions;•others may design around our intellectual property rights or independently develop similar or alternative technologies or duplicate any of ourtechnologies without infringing or misappropriating our intellectual property rights;•it is possible that our pending patent applications will not lead to issued patents with claims that cover our products or even issued patents;•issued patents that we own or have exclusively licensed may not provide us with any competitive advantages, or may be held invalid orunenforceable as a result of legal challenges;•our competitors might conduct research and development activities in the United States and other countries that provide a safe harbor from patentinfringement claims for certain research and development activities, as well as in countries where we do not have patent rights and then use theinformation learned from such activities to develop competitive products for sale in our major commercial markets;•we may not develop additional proprietary technologies or product candidates that are patentable; and•the intellectual property rights of others may have an adverse effect on our business.Risks Related to Regulatory and Marketing Approval of Our Product Candidates and Other Legal Compliance MattersIf we are not able to obtain required regulatory approvals, or there are delays in obtaining approvals, we will not be able to commercialize any productcandidate that we may develop, and our ability to generate revenue will be materially impaired. The marketing approval process is expensive, time-consuming and uncertain. As a result, we cannot predict when or if we, or any licensees or collaborators, will obtain marketing approval to commercializeany product candidate.82Table of ContentsTo date, we have not obtained approval from the FDA or any foreign regulatory authority, including Health Canada and the European Commission, to marketor sell any of our product candidates. The failure to obtain marketing approval for a product candidate will prevent us from commercializing the productcandidate. The activities associated with the development and commercialization of our product candidates, including design, testing, manufacture, quality,safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDAand other regulatory agencies in the United States and by the EMA, the competent authorities of the E.U. Member States, Health Canada and similarregulatory authorities outside the United States. We have only limited experience in filing and supporting the applications necessary to gain marketingapprovals and expect to rely on third-party CROs to assist us in this process.The process of obtaining marketing approvals, both in the United States and abroad, is expensive and may take many years, especially if additional clinicaltrials are required, if approval is obtained at all. Securing marketing approval requires the submission of extensive pre-clinical and clinical data andsupporting information to regulatory authorities for each therapeutic indication to establish the product candidate’s quality, safety, and efficacy. Securingmarketing approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by,the regulatory authorities. The FDA, Health Canada, EMA or other regulatory authorities may determine that any product candidate that we may develop isnot safe, effective or of appropriate quality, is only moderately effective or has undesirable or unintended side effects, toxicities or other characteristics thatpreclude our obtaining marketing approval or prevent or limit commercial use. Any marketing approval we ultimately obtain may be limited or subject torestrictions or post-approval commitments that render the approved product not commercially viable.The regulatory process can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved.Moreover, changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, orchanges in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application. The FDA andcomparable regulatory authorities in other countries, including Health Canada and the European Commission, have substantial discretion in the approvalprocess and may refuse to accept any application or may decide that our data is insufficient for approval and require additional pre-clinical, clinical or otherstudies. In addition, varying interpretations of the data obtained from pre-clinical and clinical testing could delay, limit or prevent marketing approval of aproduct candidate. In February 2018, the FDA issued finalized guidance on developing drugs and biologics for treating BCG-unresponsive NMIBC, whichsets forth certain expectations for our development of Vicinium for the treatment of high-risk NMIBC. We may be unable to satisfy all recommendationscontained in the FDA guidance and, even if we do, it is not guaranteed that meeting all such recommendations will be sufficient to obtain marketingapproval.The different requirements and expectations of the EMA and Health Canada compared with the FDA may lengthen the regulatory review process, require usto conduct additional studies or clinical trials, increase our development costs, lead to changes in regulatory positions and interpretations, delay or preventapproval and commercialization of these product candidates or lead to significant post approval limitations or restrictions. If we experience delays inobtaining regulatory approvals, the commercial prospects for our product candidates may be harmed and our ability to generate revenues will be materiallyimpaired.Some of our product candidates may qualify for orphan drug designation, and if we obtain approval for these product candidates, orphan drug exclusivitymay afford limited protection. If another party obtains orphan drug exclusivity before we do for the same drug for the same indication we are targeting, wemay be precluded from commercializing our product candidate in that indication until the other party’s period of exclusivity has ended.Regulatory authorities in some jurisdictions, including the United States and the E.U., may designate drugs and biologics intended to treat relatively smallpatient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is a biologic intended to treat a raredisease or condition, which generally means a disease or condition that affects fewer than 200,000 individuals in the United States. The first BLA applicantwith an orphan drug designation that receives FDA approval is entitled to a seven-year period of orphan drug exclusivity in the United States, during whichthe FDA generally may not approve another application for a product with the same principal molecular structural features for the same indication. In theE.U., following the opinion of the EMA’s Committee for Orphan Medicinal Products, the European Commission grants orphan drug designation to a productif (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects nomore than five in 10,000 persons in the E.U. when the application is made, or (b) the product, without the incentives derived from orphan medicinal productstatus, would not generate sufficient return in the E.U. to justify investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatmentof such condition authorized for marketing in the E.U., or if such a method exists, the product will be of significant benefit to those affected by the condition.Once authorized, orphan medicinal products are entitled to ten years of market exclusivity.83Table of ContentsWe have obtained orphan drug designation from the FDA and the European Commission for Vicinium to treat EpCAM-positive SCCHN, and whereappropriate we intend to seek orphan drug designation for our other product candidates. In the U.S., we cannot assure that any or all of our product candidatesthat receive orphan drug designation will, upon approval, have seven years of orphan drug exclusivity. The FDA may revoke orphan drug designation undercertain circumstances, including if the agency determines that the request for orphan drug designation omitted material information or subsequently findsthat the biologic had not been eligible for orphan drug designation at the time the request for designation was submitted. Revocation of orphan drugdesignation suspends the associated orphan drug exclusivity. Also, the FDA may approve another sponsor’s application for the same drug for the same use,prior to the expiration of our product’s orphan drug exclusivity, under certain circumstances, including if we are unable to assure sufficient quantity of ourproduct, or if the other sponsor can demonstrate that its product candidate is clinically superior to ours by showing superior safety or efficacy or a majorcontribution to patient care. In addition, if a competitor obtains approval and orphan drug exclusivity for a product that is the same as a product candidate weare pursuing for the same indication, approval of our product candidate would be blocked during the period of the competitor’s orphan drug exclusivity,unless we could demonstrate that our product candidate is clinically superior to the approved product. Also, if a competitor obtains approval for a drug that isthe same as a product candidate we are pursuing for a different orphan indication, the competitor’s approval may negatively impact the market opportunityfor our product candidate, even if our product is granted orphan drug exclusivity.Products authorized in the E.U. as orphan medicinal products are entitled to ten years of data exclusivity. The products are, in parallel, entitled to ten years ofmarket exclusivity. The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longermeets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity. Additionally,marketing authorization may be granted to a similar product during the ten-year period of market exclusivity for the same therapeutic indication at any timeif:•The second applicant can establish in its application that its product, although similar to the orphan medicinal product already authorized, is safer,more effective or otherwise clinically superior;•The holder of the marketing authorization for the original orphan medicinal product consents to a second orphan medicinal product application; or•The holder of the marketing authorization for the original orphan medicinal product cannot supply enough orphan medicinal product.Our product candidates for which we intend to seek approval as biological products may face competition sooner than expected from biosimilar products.With the enactment of the BPCIA, abbreviated pathways for approval of biosimilar and interchangeable biological products were created. The BPCIAestablishes legal authority for the FDA to review and approve biosimilars for marketing, as well as biosimilars that have been designated as “interchangeable”with a previously approved biologic, or reference product. Under the BPCIA, an application for a biosimilar product cannot be approved by the FDA until 12years after the reference product was approved under a full BLA. This period of regulatory exclusivity runs concurrently with, but is independent of, periodsof patent protection for the reference product.We believe that any of our product candidates approved as a biological product under a full BLA should qualify for a 12-year period of exclusivity.However:•the United States Congress could amend the BPCIA to significantly shorten this exclusivity period as has been previously proposed; and•a potential competitor could seek and obtain approval of its own BLA during our exclusivity period instead of seeking approval of abiosimilar version.The BPCIA is complex and its provisions continue to be interpreted and implemented by the FDA and U.S. courts. As a result, the ultimate impact,implementation and implications of the BPCIA are subject to uncertainty and could compromise the future commercial prospects for our biological products.Moreover, it is not yet clear the extent to which a biosimilar, once approved, may be substituted for any one of our reference products in a way that is similarto traditional generic substitution for pharmaceutical products; this will depend on a number of marketplace and regulatory factors that are still developing atboth the federal and state levels of government.Failure to obtain marketing approval in foreign jurisdictions would prevent our product candidates from being marketed abroad, and any approval weare granted for our product candidates in the United States would not assure approval of product candidates in foreign jurisdictions.84Table of ContentsIn order to market and sell any product candidate that we may develop in the E.U., Canada and many other jurisdictions, we or our third-party licensees orcollaborators must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure variesamong countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval.The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in manycountries outside the United States it is required that the product be approved for reimbursement before the product can be sold in that country. We or thesethird parties may not obtain approvals from regulatory authorities outside the United States, including Health Canada, or the European Commission, on atimely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by oneregulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. We maynot be able to file for marketing approvals and may not receive necessary approvals to commercialize our products in any market. If we are unable to obtainapproval of our product candidates by regulatory authorities in Canada, the E.U. or other jurisdictions, the commercial prospects of our product candidatesmay be significantly diminished and our business prospects could decline.Even if we, or our third-party licensees or collaborators, obtain marketing approvals for our product candidates, the terms of those approvals, ongoingregulations and post-marketing restrictions may limit how we, or they, manufacture and market our products, which could materially impair our ability togenerate revenue.Once marketing approval has been granted, an approved product and its manufacturer and marketer are subject to ongoing review and extensive regulation.We, and any collaborators we may have in the future, must therefore comply with requirements concerning advertising and promotion for any of our productsfor which we or they obtain marketing approval. Promotional communications with respect to prescription products are subject to a variety of legal andregulatory restrictions and must be consistent with the information in the product’s approved labeling. Thus, if any product candidate that we may developreceives marketing approval, the accompanying label may limit the approved use of our product, which could limit sales of the product.In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA requirements, includingensuring that quality control and manufacturing procedures conform to cGMPs, which include requirements relating to quality control and quality assuranceas well as the corresponding maintenance of records and documentation and reporting requirements. We, our contract manufacturers, our future collaboratorsand their contract manufacturers will also be subject to other regulatory requirements, including submissions of safety and other post-marketing informationand reports, registration and listing requirements, requirements regarding the distribution of samples to physicians, recordkeeping, and potentially costlypost-marketing studies or other clinical trials and surveillance to monitor the safety or efficacy of the product such as the requirement to implement a riskevaluation and mitigation strategy.Accordingly, assuming we receive marketing approval for one or more of our product candidates, we and our contract manufacturers will continue to expendtime, money and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance and quality control. If we are notable to comply with post-approval regulatory requirements, we could have the marketing approvals for our products withdrawn by regulatory authorities andour ability to market any future products could be limited, which could adversely affect our ability to achieve or sustain profitability. Thus, the cost ofcompliance with post-approval regulations may have a negative effect on our operating results and financial condition.Any product candidate for which we obtain marketing approval will be subject to a strict enforcement of post-marketing requirements and we could besubject to substantial penalties, including withdrawal of our product from the market, if we fail to comply with all regulatory requirements or if weexperience unanticipated problems with our products, when and if any of them are approved.Any product candidate for which we obtain marketing approval, along with the manufacturing processes, post-approval clinical trials, labeling, advertisingand promotional activities for such product, will be subject to continual requirements of and review by the FDA and other federal and state regulatoryauthorities. These requirements include, but are not limited to, restrictions governing promotion of an approved product, submissions of safety and otherpost-marketing information and reports, registration and listing requirements, cGMP requirements relating to manufacturing, quality control, qualityassurance and corresponding maintenance of records and documents, and requirements regarding the distribution of samples to physicians andrecordkeeping. The respective safety and efficacy profiles of our product candidates will continue to be closely monitored by the FDA and comparableforeign regulatory authorities, including Health Canada, if they are approved. If new safety information becomes available after approval of our productcandidates, the FDA may require labeling changes or establishment of a REMS, and the FDA or comparable foreign regulatory authorities, including HealthCanada, may require a similar strategy, impose significant restrictions on our product candidates’ indicated uses or marketing, or impose ongoingrequirements for potentially costly post-approval studies or post-market surveillance.85Table of ContentsThe FDA and other federal and state agencies, including the DOJ closely regulate compliance with all requirements governing prescription drug products,including requirements pertaining to marketing and promotion of drugs in accordance with the provisions of the approved labeling and manufacturing ofproducts in accordance with cGMP requirements. Violations of such requirements may lead to investigations alleging violations of the FDCA and otherstatutes, including the False Claims Act and other federal and state health care fraud and abuse laws as well as state consumer protection laws. In the UnitedStates, engaging in impermissible promotion of approved products for off-label uses can also subject us to false claims litigation under federal and statestatutes, and other litigation and/or investigation, which can lead to civil and criminal penalties and fines and agreements that materially restrict the mannerin which we promote or distribute our drug products. These false claims statutes include the federal civil False Claims Act, which allows any individual tobring a lawsuit against a pharmaceutical company on behalf of the federal government alleging submission of false or fraudulent claims, or causing to presentsuch false or fraudulent claims, for payment by a federal program such as Medicare or Medicaid. If the government prevails in the lawsuit, the individual willshare in any fines or settlement funds. These False Claims Act lawsuits against pharmaceutical companies have increased significantly in volume andbreadth, leading to several substantial civil and criminal settlements based on certain sales practices promoting off-label drug uses. This increasing focus andscrutiny has increased the risk that a pharmaceutical company will have to defend a false claim action, pay settlement fines or restitution, agree to complywith burdensome reporting and compliance obligations, or risk being excluded from the Medicare, Medicaid and other federal and state healthcare programs.If we do not lawfully promote our approved products, we may become subject to such litigation and/or investigation and, if we are not successful indefending against such actions, those actions could compromise our ability to become profitable. Our failure to comply with all regulatory requirements, andlater discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, may yield variousresults, including:•litigation involving patients taking our products;•restrictions on such products, manufacturers or manufacturing processes;•restrictions on the labeling or marketing of a product;•restrictions on product distribution or use;•requirements to conduct post-marketing studies or clinical trials;•warning letters or untitled letters;•withdrawal of the products from the market;•refusal to approve pending applications or supplements to approved applications that we submit;•recall of products;•fines, restitution or disgorgement of profits or revenues;•suspension or withdrawal of marketing approvals;•damage to relationships with any potential collaborators;•unfavorable press coverage and damage to our reputation;•refusal to permit the import or export of our products;•product seizure or detention; or•injunctions or the imposition of civil or criminal penalties.The occurrence of any event or penalty described above may inhibit or preclude our ability to commercialize our product candidates and generate revenue.Non-compliance by us or any future collaborator with regulatory requirements regarding safety monitoring or pharmacovigilance, and with requirementsrelated to the development of products for the pediatric population, can also result in significant financial penalties.Our failure to comply with data protection laws and regulations could lead to government enforcement actions and significant penalties against us, andadversely impact our operating results.We are subject to U.S. data protection laws and regulations (i.e., laws and regulations that address privacy and data security) at both the federal and statelevels. The legislative and regulatory landscape for data protection continues to evolve, and in recent years there has been an increasing focus on privacy anddata security issues. Numerous federal and state laws, including state data breach notification laws, state health information privacy laws, and federal andstate consumer protection laws, govern the86Table of Contentscollection, use, and disclosure of health-related and other personal information. In addition, we may obtain health information from third parties (e.g.,healthcare providers who prescribe our products) that are subject to privacy and security requirements under Health Insurance Portability and AccountabilityAct of 1996, or HIPAA. Although we are not directly subject to HIPAA-other than potentially with respect to providing certain employee benefits-we couldbe subject to criminal penalties if we knowingly obtain or disclose individually identifiable health information maintained by a HIPAA-covered entity in amanner that is not authorized or permitted by HIPAA. Finally, a data breach affecting sensitive personal information, including health information, couldresult in significant legal and financial exposure and reputational damages that could potentially have an adverse effect on our business.E.U. Member States, Switzerland and other countries have also adopted data protection laws and regulations, which impose significant complianceobligations. For example, the collection and use of personal health data in the E.U. is governed by the provisions of the E.U. Data Protection Directive, or theDirective. The Directive and the national implementing legislation of the E.U. Member States impose strict obligations and restrictions on the ability tocollect, analyze and transfer personal data, including health data from clinical trials and adverse event reporting. In particular, these obligations andrestrictions concern the consent of the individuals to whom the personal data relates, the information provided to the individuals, notification of dataprocessing obligations to the competent national data protection authorities and the security and confidentiality of the personal data. Data protectionauthorities from the different E.U. Member States may interpret the Directive and national laws differently and impose additional requirements, which add tothe complexity of processing personal data in the E.U.Guidance on implementation and compliance practices are often updated or otherwise revised. For example, the E.U. Data Protection Directive prohibits thetransfer of personal data to countries outside of the European Economic Area, or EEA, that are not considered by the European Commission to provide anadequate level of data protection. These countries include the United States.The judgment by the Court of Justice of the E.U. in the Schrems case (Case C-362/14 Maximillian Schrems v. Data Protection Commissioner) determined theU.S.-E.U. Safe Harbor Framework, which was relied upon by many U.S. entities as a basis for transfer of personal data from the E.U. to the U.S., to be invalid.U.S. entities therefore, had only the possibility to rely on the alternate procedures for such data transfer provided in the E.U. Data Protection Directive.On February 29, 2016, however, the European Commission announced an agreement with the U.S. Department of Commerce, or DOC, to replace theinvalidated Safe Harbor framework with a new E.U.-U.S “Privacy Shield”. On July 12, 2016, the European Commission adopted a decision on the adequacyof the protection provided by the Privacy Shield. The Privacy Shield is intended to address the requirements set out by the Court of Justice of the E.U. in itsSchrems judgment by imposing more stringent obligations on companies, providing stronger monitoring and enforcement by the DOC and the Federal TradeCommission, and making commitments on the part of public authorities regarding access to information. U.S. companies have been able to certify to the DOCtheir compliance with the privacy principles of the Privacy Shield since August 1, 2016 and rely on the Privacy Shield certification to transfer of personaldata from the E.U. to the U.S.On September 16, 2016, the Irish privacy advocacy group Digital Rights Ireland brought an action for annulment of the European Commission decision onthe adequacy of the Privacy Shield before the Court of Justice of the E.U. (Case T-670/16). Case T-670/16 is still pending. If the Court of Justice of the E.U.invalidates the Privacy Shield, it will no longer be possible to rely on the Privacy Shield certification to transfer personal data from the E.U. to entities in theU.S. Adherence to the Privacy Shield is not, however, mandatory. U.S.-based companies are permitted to rely either on their adherence to the E.U.-US PrivacyShield or on the other authorized means and procedures to transfer personal data provided by the E.U. Data Protection Directive.In addition, the E.U. Data Protection Regulation, intended to replace the current E.U. Data Protection Directive entered into force on May 24, 2016 and willapply from May 25, 2018. The E.U. Data Protection Regulation will introduce new data protection requirements in the E.U. and substantial fines for breachesof the data protection rules. The E.U. Data Protection Regulation will increase our responsibility and liability in relation to personal data that we process, andwe may be required to put in place additional mechanisms to ensure compliance with the new data protection rules.Our failure to comply with these laws, or changes in the way in which these laws are implemented, could lead to government enforcement actions andsignificant penalties against us, and adversely impact our business.Our relationships with customers and third-party payors may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims,transparency, health information privacy and security, and other healthcare laws and regulations, which could expose us to criminal sanctions, civilpenalties, contractual damages, reputational harm, administrative burdens and diminished profits and future earnings.87Table of ContentsHealthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription ofany product candidate for which we obtain marketing approval. Our future arrangements with third-party payors and customers may expose us to broadlyapplicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships throughwhich we market, sell and distribute any products for which we obtain marketing approval. In addition, we may be subject to transparency laws and patientprivacy regulation by U.S. federal and state governments and by governments in foreign jurisdictions in which we conduct our business. The applicablefederal, state and foreign healthcare laws and regulations that may affect our ability to operate include:•the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, offering, receivingor providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individualfor, or the purchase, order or recommendation or arranging of, any good or service, for which payment may be made under a federalhealthcare program such as Medicare and Medicaid;•the federal False Claims Act imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, againstindividuals or entities for, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment bya federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing orconcealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages andsignificant per-claim penalties, set at $10,781 to $21,563 per false claim for violations occurring after November 2, 2015;•HIPAA, which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or knowingly andwillfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement orrepresentation, or making or using any false writing or document knowing the same to contain any materially false, fictitious or fraudulentstatement or entry relating to the delivery of or payment for healthcare benefits, items or services;•the federal Physician Payments Sunshine Act requires applicable manufacturers of covered products to report payments and other transfersof value to physicians and teaching hospitals;•HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, and their respectiveimplementing regulations, which imposes obligations, including mandatory contractual terms, on covered healthcare providers, healthplans and healthcare clearinghouses, as well as their business associates, with respect to safeguarding the privacy, security and transmissionof individually identifiable health information; and•analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws and transparency statutes, which mayapply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-partypayors, including private insurers; state and foreign laws that require pharmaceutical companies to comply with the pharmaceuticalindustry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwiserestrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report informationrelated to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; state laws thatprohibit certain marketing-related activities, including the provision of gifts, meals, or other items to certain health care providers, andrestrict the ability of manufacturers to offer co-pay support to patients for certain prescription drugs; state laws that require identification orlicensing of sales representatives; and state and foreign laws governing the privacy, security, collection, use and disclosure of healthinformation, including state data breach notification laws, state health information privacy laws, and federal and state consumer protectionlaws (e.g., Section 5 of the FTC Act), many of which differ from each other in significant ways and often are not preempted by HIPAA, thuscomplicating compliance efforts.Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations may involve substantial costs.It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case lawinvolving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any othergovernmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, including, without limitation,damages, fines, imprisonment, exclusion from participation in government funded healthcare programs, such as Medicare and Medicaid, and the curtailmentor restructuring of our operations. If any of the physicians or other healthcare providers or88Table of Contentsentities with whom we expect to do business is found to be not in compliance with applicable laws, it may be subject to criminal, civil or administrativesanctions, including exclusions from participation in government funded healthcare programs.Current and future legislation may increase the difficulty and cost for us and any collaborators to obtain marketing approval of our product candidatesand affect the prices we, or they, may obtain.In the United States and some foreign jurisdictions, there have been, and continue to be, a number of legislative and regulatory changes and proposedchanges regarding the healthcare system that could, among other things, prevent or delay marketing approval of our product candidates, restrict or regulatepost-approval activities and affect our ability, or the ability of any collaborators, to profitably sell any products for which we, or they, obtain marketingapproval. We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coveragecriteria and in additional downward pressure on the price that we, or any collaborators, may receive for any approved products.In the United States, the Medicare Modernization Act, established the Medicare Part D program and generally authorized prescription drug plan sponsors toimpose limits on the number of covered drugs under their plans in a therapeutic class. The Medicare Modernization Act, including its cost reductioninitiatives, could decrease the coverage and reimbursement rate that we may receive for any of our product candidates, if approved. CMS, the agency thatadministers the Medicare program, also may revise reimbursement and implement coverage restrictions. Cost reduction initiatives and changes in coveragecould decrease utilization of and reimbursement for any approved products, which would then affect the price we can receive. Private payors often followMedicare coverage policy and payment limitations in setting their own reimbursement rates. Therefore, any reduction in reimbursement from federallegislation or regulation may lead to similar reductions in private payor reimbursement.In addition, in March 2010, President Obama signed into law the Affordable Care Act. Among the provisions of the Affordable Care Act of potentialimportance to our business and our product candidates are the following:•an annual, non-deductible fee on any entity that manufactures or imports specified branded prescription products and biologic agents;•an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program;•a new methodology by which average manufacturer price is calculated and reported by manufacturers for products that are inhaled, infused,instilled, implanted or injected and not generally dispensed through retail community pharmacies;•expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal Anti-Kickback Statute, new governmentinvestigative powers and enhanced penalties for noncompliance;•a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% point-of-sale discounts offnegotiated prices of applicable brand products to eligible beneficiaries during their coverage gap period, as a condition for themanufacturer’s outpatient products to be covered under Medicare Part D;•extension of manufacturers’ Medicaid rebate liability from fee-for-service Medicaid utilization to include the utilization of Medicaidmanaged care organizations as well;•expansion of eligibility criteria for Medicaid programs;•expansion of the entities eligible for discounts under the Public Health Service 340B drug pricing program;•new requirements to report certain financial arrangements with physicians and teaching hospitals;•a new requirement to annually report product samples that manufacturers and distributors provide to physicians;•a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectivenessresearch, along with funding for such research; and•establishment of the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models.Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. These changes include the Budget Control Act of2011, which, among other things, led to aggregate reductions to Medicare payments for all items and services to providers of up to 2% per fiscal year thatstarted in 2013 and, due to subsequent legislation, will continue until 2025.89Table of ContentsIn addition, the American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several types of providers and increased thestatute of limitations period for the government to recover overpayments to providers from three to five years. These new laws may result in additionalreductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which regulatoryapproval is obtained, which could have a material adverse effect on our financial operations.Additional legislative changes, FDA or CMS regulations, or guidance or interpretations could be adopted, which may impact the marketing approvals andreimbursement for our product candidates. For example, there have been several Congressional inquiries and proposed bills and regulatory initiativesdesigned to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs,and reform government program reimbursement methodologies for drug products in November 2015, the U.S. House of Representatives formed anAffordable Drug Pricing Task Force to advance legislation intended to control pharmaceutical drug costs and investigate pharmaceutical drug pricing, andthe U.S. Senate has requested information from certain pharmaceutical companies in connection with an investigation into pharmaceutical drug pricingpractices. If healthcare policies or reforms intended to curb healthcare costs are adopted or if we experience negative publicity with respect to pricing of ourproducts or the pricing of pharmaceutical drugs generally, the prices that we charge for any approved products may be limited, our commercial opportunitymay be limited and/or our revenues from sales of our products may be negatively impacted.Some of the provisions of the Affordable Care Act have yet to be fully implemented, and certain provisions have been subject to judicial and Congressionalchallenges. In addition, there have been efforts by the Trump administration to repeal or replace certain aspects of the ACA and to alter the implementation ofthe ACA and related laws. Certain legislative changes to and regulatory changes under the Affordable Care Act have occurred in the 115th United StatesCongress and under the Trump Administration. For example, the Tax Cuts and Jobs Act enacted on December 22, 2017, eliminated the tax-based sharedresponsibility payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code of 1986,commonly referred to as the “individual mandate,” effective January 1, 2019. Further, the Bipartisan Budget Act of 2018 among other things, amended theMedicare statute, effective January 1, 2019, to reduce the coverage gap in most Medicare drug plans, commonly known as the “donut hole,” by raising themanufacturer discount under the Medicare Part D coverage gap discount program to 70%. Additional legislative changes, to and regulatory changes, andjudicial challenges related to under the Affordable Care Act remain possible. It is unclear how the Affordable Care Act and its implementation, as well asefforts to repeal or replace, or invalidate, the Affordable Care Act, or portions thereof, will affect our business. It is possible We expect that the AffordableCare Act, as currently enacted or may be amended in the future, as well as other healthcare reform measures that may be adopted in the future, may result inadditional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, and new payment methodologies and additional downwardpressure on coverage and payment and on the price that we receive for any approved product. Any reduction in reimbursement from Medicare or othergovernment programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or otherhealthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products. Moreover, legislative andregulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. Wecannot be sure whether additional legislative changes will be enacted in the U.S. or outside of the U.S., or whether the FDA or CMS regulations, guidance orinterpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be.If we participate in the Medicaid drug rebate program and fail to comply with our reporting and payment obligations under that or other governmentalpricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverseeffect on our business, financial condition, results of operations and growth prospects.If we participate in the Medicaid drug rebate program, we will have certain price reporting obligations to the Medicaid drug rebate program, and we mayhave obligations to report ASP figures to the Medicare program. Under the Medicaid drug rebate program, we would be required to pay a rebate to each stateMedicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program as a condition ofhaving federal funds being made available to the states for our drugs under Medicaid and Medicare Part B. Those rebates are based on pricing data reportedby us to CMS. These data include AMP and, in the case of innovator products, the best price for each drug which, in general, represents the lowest priceavailable from the manufacturer to any entity in the United States in any pricing structure, calculated to include all sales and associated rebates, discountsand other price concessions.Federal law also requires that a company that participates in the Medicaid drug rebate program report ASP information each quarter to CMS for certaincategories of drugs that are paid under Part B of the Medicare program. Manufacturers calculate90Table of ContentsASP based on a statutorily defined formula and interpretations of the statute by CMS. CMS uses these submissions to determine payment rates for drugsunder Medicare Part B and the resulting Medicare payment rate.Federal law requires that any company that participates in the Medicaid drug rebate program also participate in the Public Health Service’s 340B drugpricing program in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B. The 340B drug pricing programrequires participating manufacturers to agree to charge statutorily-defined covered entities no more than the 340B “ceiling price” for the manufacturer’scovered outpatient drugs. In addition, in order to be eligible to have its products paid for with federal funds under the Medicaid and Medicare Part Bprograms and purchased by certain federal agencies and grantees, a manufacturer also must participate in the FSS pricing program, established by Section603 of the Veterans Health Care Act of 1992. Under this program, the manufacturer is obligated to make its “covered drugs” (biologics or innovator drugs)available for procurement on an FSS contract and charge a price to four federal agencies, Department of Veterans Affairs, Department of Defense, PublicHealth Service, and Coast Guard, that is no higher than the statutory federal ceiling price. The HRSA, which administers the 340B drug pricing program,issued a final regulation regarding the calculation of the 340B ceiling price and the imposition of civil monetary penalties on manufacturers that knowinglyand intentionally overcharge covered entities, which became effective on January 1, 2019. HRSA also has begun to implement a ceiling price reportingrequirement during the first quarter of 2019, pursuant to which manufacturers must report the 340B ceiling prices for their covered outpatient drugs on aquarterly basis. The requirements under the 340B and FSS programs could reduce the revenue we may generate from any products that are commercialized inthe future and could adversely affect our business and operating results.Pricing and rebate calculations vary among products and programs. The calculations are complex and are often subject to interpretation by manufacturers,governmental or regulatory agencies, and the courts. The Medicaid rebate amount for each manufacturer is computed each quarter based on themanufacturer’s submission to CMS of its current AMP and, in the case of innovator products, best price figures, for the quarter. If we participate in theMedicaid drug rebate program and become aware that our reporting for a prior quarter was incorrect, or has changed, we will be obligated to resubmit thecorrected data for a period not to exceed twelve quarters from the quarter in which the data originally were due. Such restatements and recalculations wouldincrease our costs for complying with the laws and regulations governing the Medicaid drug rebate program. Any corrections to our rebate calculationscould result in an overage or underage in our rebate liability for past quarters, depending on the nature of the correction. Price recalculations also may affectthe ceiling price at which we would be required to offer our products to certain covered entities, such as safety-net providers, under the 340B drug pricingprogram, and we may be obligated to issued refunds to covered entities.If we participate in the Medicaid drug rebate program or our products are covered under Medicare Part B, we will be liable for errors associated with oursubmission of pricing data. We cannot assure you that our submissions, if we participate in these programs, will not be found by CMS to be incomplete orincorrect. In addition to retroactive rebates and the potential for 340B program refunds, if we are found to have knowingly submitted false AMP, ASP, or bestprice information to the government, we may be liable for civil monetary penalties per item of false information. If we are found to have made amisrepresentation in the reporting of our ASP, the Medicare statute provides for civil monetary penalties for each misrepresentation for each day in which themisrepresentation was applied. Civil monetary penalties also can be applied if we are found to have intentionally charged 340B covered entities more thanthe statutorily mandated ceiling price. Our failure to submit monthly/quarterly AMP, ASP, and best price data on a timely basis could result in a civilmonetary penalty per day for each day the information is late beyond the due date. Such failure also could be grounds for CMS to terminate our Medicaiddrug rebate agreement, pursuant to which we would participate in the Medicaid program. In the event that CMS terminates our rebate agreement, federalpayments may not be available under Medicaid or Medicare Part B for our covered outpatient drugs that we are able to successfully commercialize.Laws and regulations governing any international operations we may have in the future may preclude us from developing, manufacturing and sellingcertain products outside of the United States and require us to develop and implement costly compliance programs.If we expand our operations outside of the United States, we must dedicate additional resources to comply with numerous laws and regulations in eachjurisdiction in which we plan to operate. The FCPA prohibits any U.S. individual or business from paying, offering, authorizing payment or offering ofanything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreignentity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in theUnited States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect alltransactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls forinternational operations.91Table of ContentsCompliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the FCPA presentsparticular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospitalemployees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improperpayments to government officials and have led to FCPA enforcement actions.Various laws, regulations and executive orders also restrict the use and dissemination outside of the United States, or the sharing with certain non-U.S.nationals, of information classified for national security purposes, as well as certain products and technical data relating to those products. If we expand ourpresence outside of the United States, it will require us to dedicate additional resources to comply with these laws, and these laws may preclude us fromdeveloping, manufacturing, or selling certain products and product candidates outside of the United States, which could limit our growth potential andincrease our development costs.The failure to comply with laws governing international business practices may result in substantial civil and criminal penalties and suspension or debarmentfrom government contracting. The Securities and Exchange Commission, or SEC, also may suspend or bar issuers from trading securities on U.S. exchangesfor violations of the FCPA’s accounting provisions.The results of the United Kingdom’s referendum on withdrawal from the E.U. may have a negative effect on global economic conditions, financial marketsand our business.In June 2016, a majority of voters in the United Kingdom elected to withdraw from the E.U. in a national referendum. In March 2017, the government of theUnited Kingdom formally initiated the withdrawal procedure. The procedure involves a two-year negotiation period in which the United Kingdom and theE.U. must conclude an agreement setting out the terms of the United Kingdom's withdrawal and the arrangements for the United Kingdom's futurerelationship with the E.U. In the absence of an agreement within this timeframe, the U.K. will automatically leave the EU without a deal. This negotiationperiod could be extended by a unanimous decision of the European Council, in agreement with the United Kingdom. The United Kingdom could alsounilaterally revoke its notification to withdraw from the EU. The referendum has created significant uncertainty about the future relationship between theUnited Kingdom and the E.U., including with respect to the laws and regulations that will apply as the United Kingdom determines which E.U. laws toreplace or replicate in the event of a withdrawal. From a regulatory perspective, the United Kingdom's withdrawal could bear significant complexity and legalrisks. A basic requirement related to the grant of a marketing authorization for a medicinal product in the E.U. is that the applicant is established in the E.U.Following the withdrawal of the United Kingdom from the E.U., marketing authorizations previously granted to applicants established in the UnitedKingdom may no longer be valid in the E.U. Moreover, depending upon the exact terms of the United Kingdom's withdrawal, there is an arguable risk that thescope of a marketing authorization for a medicinal product granted by the European Commission pursuant to the centralized procedure would not, in thefuture, include the United Kingdom. In these circumstances, an authorization granted by the United Kingdom's competent authorities would always berequired to place medicinal products on the United Kingdom market. In addition, the laws and regulations that will apply after the United Kingdomwithdraws from the E.U. would affect the manufacturing sites that hold a manufacturing authorization issued by the United Kingdom competent authorities.Our capability to rely on these manufacturing sites for products intended for the E.U. market would also depend upon the exact terms of the UnitedKingdom's withdrawal. The referendum has also given rise to calls for the governments of other E.U. Member States to consider withdrawal from the E.U.These developments, or the perception that any of them could occur, have had and may continue to have a material adverse effect on global economicconditions and the stability of global financial markets, and may significantly reduce global market liquidity and restrict the ability of key marketparticipants to operate in certain financial markets. Any of these factors could significantly increase the complexity of our activities in the E.U. and in theUnited Kingdom, could depress our economic activity and restrict our access to capital, which could have a material adverse effect on our business, financialcondition and results of operations and reduce the price of our securities.If we or our third-party manufacturers fail to comply with environmental, health and safety laws and regulations, we could become subject to fines orpenalties or incur significant costs.We and our third-party manufacturers are subject to numerous environmental, health and safety laws and regulations, including those governing laboratoryprocedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. From time to time and in the future, our operations mayinvolve the use of hazardous and flammable materials, including chemicals and biological materials, and produce hazardous waste products. We generallycontract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury from these materials. In theevent of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability couldexceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws andregulations.92Table of ContentsAlthough we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from theuse of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmentalliability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current orfuture laws and regulations may impair our research, development or production efforts. Our failure to comply with these laws and regulations also may resultin substantial fines, penalties or other sanctions.Further, with respect to the operations of our third-party contract manufacturers, it is possible that if they fail to operate in compliance with applicableenvironmental, health and safety laws and regulations or properly dispose of wastes associated with our products, we could be held liable for any resultingdamages, suffer reputational harm or experience a disruption in the manufacture and supply of our product candidates or products.Our employees may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements, whichcould cause significant liability for us and harm our reputation.We are exposed to the risk of employee fraud or other misconduct, including intentional failure to comply with FDA regulations or similar regulations ofcomparable non-U.S. regulatory authorities, including Health Canada, failure to provide accurate information to the FDA or comparable non-U.S. regulatoryauthorities, including Health Canada or the competent authorities of the E.U. Member States, failure to comply with manufacturing standards we haveestablished, failure to comply with federal and state healthcare fraud and abuse laws and regulations and similar laws and regulations established andenforced by comparable non-U.S. regulatory authorities, and failure to report financial information or data accurately or disclose unauthorized activities tous. Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatorysanctions and serious harm to our reputation. It is not always possible to identify and deter employee misconduct, and the precautions we take to detect andprevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or otheractions or lawsuits stemming from a failure to be in compliance with such laws, standards or regulations. If any such actions are instituted against us, and weare not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations,including the imposition of significant fines or other sanctions.Risks Related to Employee Matters and Managing GrowthRecent changes in our senior management team and the lack of shared experience among the current members of our senior management team could harmour business.We have recently experienced significant changes in our senior management. Stephen A. Hurly departed as our Chief Executive Officer effective as of August7, 2018 and resigned as a member of our Board effective as of August 16, 2018. Effective as of August 7, 2018 our Board appointed Thomas R. Cannell,D.V.M., as our Chief Executive Officer and a member of our Board. On December 3, 2018, we appointed Dennis Kim, M.D., MPH as our Chief MedicalOfficer.Dr. Cannell has not worked with our existing senior management team prior to his appointment as our President and Chief Executive Officer. This lack ofshared experience could negatively impact our senior management team’s ability to quickly and efficiently respond to problems and effectively manage ourbusiness and we may experience disruption or have difficulty in maintaining or developing our business during this transition. If Dr. Cannell is unable workwith our existing management team to implement our strategies, manage our operations and accomplish our objectives, our business, operations and financialresults could be impaired.Our future success depends on our ability to attract, retain and motivate qualified personnel.Our future growth and success depend on our ability to recruit, retain, manage and motivate our employees. The loss of any member of our seniormanagement team or the inability to hire or retain experienced management personnel could compromise our ability to execute our business plan and harmour operating results. Recruiting and retaining qualified scientific, clinical, manufacturing and sales and marketing personnel will also be critical to oursuccess. The loss of the services of our executive officers or other key employees could impede the achievement of our research, development andcommercialization objectives and seriously harm our ability to successfully implement our business strategy. Furthermore, replacing executive officers andkey employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth ofskills and experience required to successfully develop, gain regulatory approval of and commercialize products. Competition to hire from this limited pool isintense, and we may be unable to hire, train, retain or93Table of Contentsmotivate these key personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similarpersonnel. We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions. In addition, we relyon consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercializationstrategy. Our consultants and advisors may be employed by employers other than us and may have commitments under consulting or advisory contracts withother entities that may limit their availability to us. If we are unable to continue to attract and retain high quality personnel, our ability to pursue our growthstrategy will be limited.We will need to grow the size of our organization, and we may experience difficulties in managing this growth.As of December 31, 2018, we had 24 full-time employees and no part-time employees, ten hold Ph.D. degrees, one is a medical doctor and one is a veterinarydoctor. As our development and commercialization plans and strategies develop, or as a result of any future acquisitions, we will need additional managerial,operational, sales, marketing, financial and other resources. Our management, personnel and systems that are currently in place may not be adequate tosupport this future growth. Future growth would impose significant added responsibilities on members of management, including:•managing our clinical trials effectively;•identifying, recruiting, maintaining, motivating and integrating additional employees;•managing our internal development efforts effectively while complying with our contractual obligations to licensors, licensees, contractors andother third parties;•improving our managerial, development, operational and finance systems; and•expanding our facilities.As our operations expand, we will need to manage additional relationships with various strategic partners, suppliers and other third parties. Our futurefinancial performance and our ability to commercialize our product candidates, if approved, and to compete effectively will depend, in part, on our ability toeffectively manage any future growth. To that end, we must be able to effectively manage our development efforts and clinical trials and hire, train andintegrate additional management, administrative and sales and marketing personnel. Our failure to accomplish any of these tasks could prevent us fromsuccessfully growing our company.We may acquire other assets or businesses, or form collaborations or make investments in other companies or technologies that could harm our operatingresults, dilute our stockholders’ ownership, incur debt or cause us to incur significant expense.As part of our business strategy, we may pursue acquisitions of assets or businesses, or strategic alliances and collaborations, to expand our existingtechnologies and operations. We may not identify or complete these transactions in a timely manner, on a cost-effective basis, or at all, and we may notrealize the anticipated benefits of any such transaction, any of which could have a detrimental effect on our financial condition, results of operations and cashflows. We may not be able to find suitable acquisition candidates, and if we make any acquisitions, we may not be able to integrate these acquisitionssuccessfully into our existing business and we may incur debt or assume unknown or contingent liabilities in connection therewith. Integration of anacquired company or assets may also disrupt ongoing operations, require the hiring of additional personnel and the implementation of additional internalsystems and infrastructure, especially the acquisition of commercial assets, and require management resources that would otherwise focus on developing ourexisting business. We may not be able to find suitable collaboration partners or identify other investment opportunities, and we may experience losses relatedto any such investments.To finance any acquisitions or collaborations, we may choose to issue debt or shares of our common stock as consideration. Any such issuance of shareswould dilute the ownership of our stockholders. If the price of our common stock is low or volatile, we may not be able to acquire other assets or companiesor fund a transaction using our stock as consideration. Alternatively, it may be necessary for us to raise additional capital for acquisitions through public orprivate financings. Additional capital may not be available on terms that are favorable to us, or at all.If we expand our development and regulatory capabilities or implement sales, marketing and distribution capabilities, we may encounter difficulties inmanaging our growth, which could disrupt our operations.To manage future growth, we must continue to implement and improve our managerial, operational and financial systems, expand our facilities and continueto recruit and train additional qualified personnel. Due to our limited financial resources and94Table of Contentsthe limited experience of our management team in managing a company with such growth, we may not be able to effectively manage the expansion of ouroperations or recruit and train additional qualified personnel. The expansion of our operations may lead to significant costs and may divert our managementand business development resources. Any inability to manage growth could delay the execution of our business plans or disrupt our operations.We rely significantly on information technology and any failure, inadequacy, interruption or security lapse of that technology, including any cybersecurity incidents, could harm our ability to operate our business effectively.Despite the implementation of security measures, our internal computer systems and those of third parties with which we contract are vulnerable to damagefrom cyber-attacks, computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. System failures,accidents or security breaches could cause interruptions in our operations, and could result in a material disruption of our clinical and commercializationactivities and business operations, in addition to possibly requiring substantial expenditures of resources to remedy. The loss of clinical trial data could resultin delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or securitybreach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incurliability and our product research, development and commercialization efforts could be delayed.Risks Related to Ownership of Our Common StockProvisions in our corporate charter documents and under Delaware law could make an acquisition of our company, which may be beneficial to ourstockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.Provisions in our certificate of incorporation and our bylaws may discourage, delay or prevent a merger, acquisition or other change in control of ourcompany that stockholders may consider favorable, including transactions in which our stockholders might otherwise receive a premium for their shares.These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the marketprice of our common stock. In addition, because our board of directors is responsible for appointing the members of our management team, these provisionsmay frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders toreplace members of our board of directors. Among other things, these provisions:•establish a classified board of directors such that only one of three classes of directors is elected each year;•allow the authorized number of our directors to be changed only by resolution of our board of directors;•limit the manner in which stockholders can remove directors from our board of directors;•establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to our boardof directors;•require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by writtenconsent;•limit who may call stockholder meetings;•authorize our board of directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” thatwould work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approvedby our board of directors; and•require the approval of the holders of at least 75% of the votes that all our stockholders would be entitled to cast to amend or repealspecified provisions of our certificate of incorporation or bylaws.Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, or DGCL,which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after thedate of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in aprescribed manner.If we are unable to regain compliance with the listing requirements of the Nasdaq Global Market, our common stock may be delisted from the NasdaqGlobal Market which could have a material adverse effect on our financial condition and could make it more difficult for you to sell your shares.95Table of ContentsOur common stock is listed on the Nasdaq Global Market, and we are therefore subject to its continued listing requirements, including requirements withrespect to the market value of publicly-held shares, market value of listed shares, minimum bid price per share, and minimum stockholders' equity, amongothers, and requirements relating to board and committee independence. If we fail to satisfy one or more of the requirements, we may be delisted from theNasdaq Global Market.On February 19, 2019, we received notice, or the Notice, from the Nasdaq Stock Market LLC, or Nasdaq, that we are not currently in compliance with the$1.00 minimum closing bid price requirement of Nasdaq Listing Rule 5550(a)(2). The Notice indicated that, consistent with Nasdaq Listing Rule 5810(c)(3)(A), we have until August 19, 2019 to regain compliance with the minimum bid price requirement by having the closing bid price of our common stock meetor exceed $1.00 per share for at least ten consecutive business days. The notification had no immediate effect on the listing of our common stock and ourcommon stock will continue to trade on the Nasdaq Global Market under the symbol “SESN” at this time.If we do not regain compliance by August 19, 2019, we may be eligible for an additional 180 calendar day grace period if we meet the continued listingrequirement for market value of publicly held shares ($1 million) and all other Nasdaq initial listing standards which require, among other things, that wehave at least $5 million of stockholders’ equity or at least $4 million of stockholders’ equity and $50 million market value of listed shares. If we fail to regaincompliance during the applicable period, we will receive notification from Nasdaq that our common stock is subject to delisting. At that time, we may thenappeal the delisting determination to a Hearings Panel. Such notification will have no immediate effect on our listing on the Nasdaq Global Market, nor willit have an immediate effect on the trading of our common stock pending such hearing. There can be no assurance, however, that we will be able to regaincompliance with Nasdaq’s minimum bid price requirement. If we regain compliance with the Nasdaq’s minimum bid price requirement, there can be noassurance that we will be able to maintain compliance with the continued listing requirements for the Nasdaq Global Market, or that our common stock willnot be delisted from the Nasdaq Global Market in the future. In addition, we may be unable to meet other applicable listing requirements of the NasdaqGlobal Market, including maintaining minimum levels of stockholders’ equity or market values of our common stock in which case, our common stock couldbe delisted notwithstanding our ability to demonstrate compliance with the minimum bid price requirement.Delisting from the Nasdaq Global Market may adversely affect our ability to raise additional financing through the public or private sale of equity securities,may significantly affect the ability of investors to trade our securities and may negatively affect the value and liquidity of our common stock. Delisting alsocould have other negative results, including the potential loss of employee confidence, the loss of institutional investors or interest in business developmentopportunities.If we are delisted from Nasdaq and we are not able to list our common stock on another exchange, our common stock could be quoted on the OTC BulletinBoard or in the “pink sheets.” As a result, we could face significant adverse consequences including, among others:•a limited availability of market quotations for our securities;•a determination that our common stock is a “penny stock” which will require brokers trading in our common stock to adhere to morestringent rules and possibly result in a reduced level of trading activity in the secondary trading market for our securities;•a limited amount of news and little or no analyst coverage for us;•we would no longer qualify for exemptions from state securities registration requirements, which may require us to comply with applicablestate securities laws; and•a decreased ability to issue additional securities (including pursuant to short-form registration statements on Form S-3) or obtain additionalfinancing in the future.If our common stock becomes subject to the penny stock rules, it would become more difficult to trade our shares.The SEC has adopted rules that regulate broker-dealer practices in connection with transactions in penny stocks. Penny stocks are generally equity securitieswith a price of less than $5.00, other than securities registered on certain national securities exchanges or authorized for quotation on certain automatedquotation systems, provided that current price and volume information with respect to transactions in such securities is provided by the exchange or system.If we do not retain our listing on the Nasdaq Global Market and if the price of our common stock is less than $5.00, our common stock may be deemed apenny stock. The penny stock rules require a broker-dealer, before a transaction in a penny stock not otherwise exempt from those rules, to deliver astandardized risk disclosure document containing specified information. In addition, the penny stock rules require that before effecting any transaction in apenny stock not otherwise exempt from those rules, a broker-dealer must make a special written determination that the penny stock is a suitable investmentfor the purchaser and receive (i) the purchaser’s written acknowledgment of the receipt of a risk disclosure statement; (ii) a written agreement to transactionsinvolving penny stocks; and (iii) a signed and dated copy of a written suitability statement. These disclosure requirements may96Table of Contentshave the effect of reducing the trading activity in the secondary market for our common stock, and therefore stockholders may have difficulty selling theirshares.The price of our common stock has been volatile and may fluctuate in the future, which could result in substantial losses for our stockholders.The price of our common stock is highly volatile and may be affected by developments directly affecting our business, as well as by developments out of ourcontrol or not specific to us. The pharmaceutical and biotechnology industries, in particular, and the stock market generally, are vulnerable to abrupt changesin investor sentiment. Prices of securities and trading volumes of companies in the pharmaceutical and biotechnology industries, including ours, can swingdramatically in ways unrelated to, or that bear a disproportionate relationship to, our performance. The price of our common stock and their trading volumesmay fluctuate based on a number of factors including, but not limited to:•the success of competitive products or technologies;•results of clinical trials of Vicinium for the treatment of high-risk NMIBC or any other product candidate that we may develop;•results of clinical trials of product candidates of our competitors;•regulatory or legal developments in the United States and other countries;•developments or disputes concerning patent applications, issued patents or other proprietary rights;•the recruitment or departure of key scientific or management personnel;•the level of expenses related to any of our product candidates or clinical development programs;•the results of our efforts to discover, develop, acquire or in-license additional products, product candidates or technologies for the treatmentof ophthalmic diseases, the costs of commercializing any such products and the costs of development of any such product candidates ortechnologies;•actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts;•variations in our financial results or those of companies that are perceived to be similar to us;•changes in the structure of healthcare payment systems;•market conditions in the pharmaceutical and biotechnology sectors;•general economic, industry and market conditions; and•the other factors described in this “Risk Factors” section.In the past, following periods of volatility in the market price of a company’s securities, securities class action litigation has often been instituted against thatcompany. We also may face securities class action litigation if we cannot obtain regulatory approvals for or if we otherwise fail to commercialize Viciniumfor the treatment of high-risk NMIBC or any of our other product candidates. Such litigation, if instituted against us, could cause us to incur substantial coststo defend such claims and divert management’s attention and resources.A significant portion of our total outstanding shares are eligible to be sold into the market, which could cause the market price of our common stock todrop significantly, even if our business is doing well.As of February 27, 2019, we had outstanding 77,456,180 shares of common stock. Of these shares, 8,348,705 shares are restricted securities under Rule 144under the Securities Act of 1933, as amended, or Securities Act. Any of our remaining shares that are not restricted securities under Rule 144 under theSecurities Act may be resold in the public market without restriction unless purchased by our affiliates.Moreover, holders of an aggregate of 7,541,729 shares of our common stock, including 3,582,328 shares of common stock issued in connection with theacquisition of Viventia, have rights, subject to specified conditions, to require us to file registration statements covering their shares or to include their sharesin registration statements that we may file for ourselves or other stockholders. We have filed registration statements on April 9, 2014, March 12, 2015, March31, 2016, May 5, 2017, May 16, 2018 and August 10, 2018 registering all shares of common stock that we may issue under our equity compensation plans.97Table of ContentsAs of February 27, 2019, we had outstanding options to purchase an aggregate of 6,052,062 shares of our common stock, of which options to purchase1,053,016 shares were vested, warrants to purchase 55,000 shares of common stock at a weighted average exercise price of $11.44 per share, warrants issuedin connection with the November 2017 Financing (as defined below) to purchase an aggregate of 1,991,687 shares of common stock at an exercise price of$0.80 per share, and, in connection with the March 2018 Financing, we also have warrants to purchase an aggregate of 7,210,945 shares of common stock atan exercise price of $1.20 per share. Shares issuable upon exercise of these options and warrants can be freely sold in the public market upon issuance, subjectto volume, notice and manner of sale limitations applicable to affiliates.Sales of a substantial number of shares of our common stock in the public market, or the perception in the market that the holders of a large number of sharesintend to sell shares, could reduce the market price of our common stock and could impair our ability to raise capital through the sale of additional equity orequity-linked securities. We are unable to predict the effect that sales may have on the prevailing market price of our common stock.Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.As of December 31, 2018, we had U.S. federal net operating loss, or NOL, carryforwards of $134.7 million, state NOL carryforwards of $129.1 million and U.S.federal and state research and development tax credit carryforwards of $2.0 million and $0.9 million, respectively. $119.3 million of the U.S. federal NOLcarryforwards and $129.1 million of the state NOL carryforwards expire beginning 2030 through 2038. $15.5 million of the U.S. federal NOL carryforwardswill be carried forward indefinitely. The U.S. federal and state tax credit carryforwards expire at various dates beginning in 2029 through 2038, if not utilized.Utilization of these NOL and tax credit carryforwards may be subject to a substantial limitation under Sections 382 and 383 of the Internal Revenue Code of1986, as amended, or the Code, and comparable provisions of state, local and foreign tax laws due to changes in ownership of our company that haveoccurred previously or that could occur in the future. Under Section 382 of the Code and comparable provisions of state, local and foreign tax laws, if acorporation undergoes an “ownership change,” generally defined as a greater than 50% change by value in its equity ownership over a three year period, thecorporation’s ability to use its pre-change NOL carryforwards and other pre-change tax attributes, such as research and development tax credits, to reduce itspost-change income may be limited. We have determined that it is more likely than not that our net operating and tax credit amounts disclosed are subject toa material limitation under Section 382. We may also experience ownership changes in the future as a result of subsequent shifts in our stock ownership. As aresult, if we generate taxable income, our ability to use our pre-change NOL and tax credits carryforwards to reduce U.S. federal and state taxable income maybe subject to limitations, which could result in increased future tax liability to us.We are an “emerging growth company,” and the reduced disclosure requirements applicable to emerging growth companies may make our common stockless attractive to investors.We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and will remain an emerging growthcompany until December 31, 2019. For so long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certaindisclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include:•not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting;•not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regardingmandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financialstatements;•reduced disclosure obligations regarding executive compensation; and•exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of anygolden parachute payments not previously approved.We have taken advantage of reduced reporting burdens in this Annual Report on Form 10-K for the annual period ended December 31, 2018, includingreduced disclosure regarding executive compensation related information that would be required if we were not an emerging growth company. We expect tocontinue, in our public reporting, to take advantage of some or all of the reporting exemptions available to emerging growth companies. We cannot predictwhether investors will find our common stock less attractive if we rely on these exemptions. If some investors find our common stock less attractive as aresult, there may be a less active trading market for our common stock and our stock price may be more volatile.In addition, the JOBS Act also provides that an emerging growth company can take advantage of an extended transition period for complying with new orrevised accounting standards. This allows an emerging growth company to delay the adoption of98Table of Contentscertain accounting standards until those standards would otherwise apply to private companies. We have irrevocably elected not to delay such adoption ofnew or revised accounting standards, and, as a result, we will comply with new or revised accounting standards on the relevant dates on which adoption ofsuch standards is required for public companies that are not emerging growth companies.We may record impairment charges, which would adversely impact our financial position and results of operations.We have recorded a material amount of goodwill and indefinite lived intangible assets on our balance sheet in connection with our acquisition of Viventia.We review our goodwill and intangible assets for impairment at least annually, or whenever events or changes in circumstances indicate that the carryingamounts of these assets may not be recoverable, in accordance with Accounting Standards Codification 350, Intangibles-Goodwill and Other.One potential indicator of goodwill impairment is whether our fair value, as measured by our market capitalization, is below our net book value. Whether ourmarket capitalization triggers an impairment charge in any future period will depend on the underlying reasons for the decline in stock price, the significanceof the decline, and the length of time the stock price has been trading at such prices.In addition, the determination as to whether our indefinite lived intangible assets related to Vicinium are impaired is heavily dependent on the results of ouron-going clinical trial, as well as other factors, such as the potential market for Vicinium, if approved.In the event that we determine in a future period that impairment exists for any reason, we would record an impairment charge, which could be material andwhich would reduce the underlying asset’s value in the period such determination is made, which would adversely impact our financial position and resultsof operations.We incur increased costs as a result of operating as a public company, and our management now is required to devote substantial time to new complianceinitiatives and corporate governance practices.As a public company, and particularly after we are no longer an emerging growth company, we will incur significant legal, accounting and other expensesthat we did not incur as a private company. The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listingrequirements of The Nasdaq Global Market and other applicable securities rules and regulations impose various requirements on public companies, includingestablishment and maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other personneldevote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have increased our legal and financial compliancecosts and will make some activities more time-consuming and costly. For example, we expect that these rules and regulations may make it more difficult andmore expensive for us to obtain director and officer liability insurance, which in turn could make it more difficult for us to attract and retain qualifiedmembers of our board of directors.We cannot predict or estimate the amount of additional costs we may incur or the timing of such costs. These rules and regulations are often subject tovarying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance isprovided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated byongoing revisions to disclosure and governance practices.For as long as we remain an emerging growth company, we may take advantage of certain exemptions from various reporting requirements that are applicableto other public companies that are not emerging growth companies as described in the preceding risk factor. We may remain an emerging growth companyuntil the end of the 2019 fiscal year.Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, we are required to furnish a report by our management on our internal controlover financial reporting. However, while we remain an emerging growth company, we will not be required to include an attestation report on internal controlover financial reporting issued by our independent registered public accounting firm. To achieve compliance with Section 404 within the prescribed period,we are engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, wecontinue to dedicate internal resources, potentially engage outside consultants and adopt a detailed work plan to assess and document the adequacy ofinternal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning asdocumented and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a riskthat we will not be able to conclude, within the prescribed timeframe or at all, that our internal control over financial reporting is effective as required bySection 404. As of December 31, 2018 we were still working to remediate a material weakness in our controls over the financial99Table of Contentsreporting process related to business combinations identified during the year ending December 31, 2016. In 2016, as a result of a lack of expertise in ourfinance and accounting group related to the accounting for business combinations, we lacked sufficient review of assumptions used and conclusions reachedfrom the perspective of a typical market participant used in the acquisition valuation model. If we fail to remedy this material weakness or identify one ormore additional material weaknesses in our internal control over financial reporting, it could result in an adverse reaction in the financial markets due to aloss of confidence in the reliability of our financial statements.If we are unable to successfully remediate the existing material weakness in our internal control over financial reporting, we could lose investorconfidence in the accuracy and completeness of our financial reports, the market price of our common stock could decline, and we could be subject tosanctions or investigations by the SEC or other regulatory authorities.In preparing our consolidated financial statements as of December 31, 2016 and 2015 and for the three years ended December 31, 2016, our managementconcluded that we had a material weaknesses in our internal control over financial reporting related to accounting for business combinations which we do notbelieve has been remediated. A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting such that thereis a reasonable possibility that a material misstatement of our financial statements will not be prevented or detected on a timely basis.The material weakness in our internal control over financial reporting was attributable primarily to our lack of expertise in our finance and accounting grouprelated to the accounting for business combinations. These deficiencies included, but were not limited to, our existing financial reporting and accountingpersonnel lacking sufficient and appropriate knowledge of U.S. GAAP and SEC rules and regulations related to business combinations. In response to thismaterial weakness, we are currently evaluating the controls and procedures we will design and put in place to address the material weakness and plan toimplement appropriate measures as part of this effort. These actions may include adding personnel, which may include one or more employees to our financeand accounting group and/or the engagement of independent consultants to aid us in our review of business combinations. However, we cannot assure youthat we will be successful in pursuing these measures or that these measures will significantly improve or remediate the material weakness described above.We also cannot assure you that we have identified all of our existing material weaknesses, or that we will not in the future have additional materialweaknesses. We have not yet remediated our material weakness, and the remediation measures that we intend to implement may be insufficient to address ourexisting material weakness or to identify or prevent additional material weaknesses.We plan to continue efforts to remediate our material weakness in this area. If we are unable to remediate this weakness, or otherwise to conclude that ourinternal control over financial reporting is effective, or if our independent auditors determine that we have a material weakness in our internal control overfinancial reporting, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of our common stock coulddecline, and we could be subject to sanctions or investigations by the SEC or other regulatory authorities.Our disclosure controls and procedures may not prevent or detect all errors or acts of fraud.We are subject to the periodic reporting requirements of the Securities Exchange Act of 1934, as amended, or Exchange Act. Our disclosure controls andprocedures are designed to reasonably assure that information required to be disclosed by us in reports we file or submit under the Exchange Act isaccumulated and communicated to management, recorded, processed, summarized and reported within the time periods specified in the rules and forms of theSEC. We believe that any disclosure controls and procedures, no matter how well conceived and operated, can provide only reasonable, not absolute,assurance that the objectives of the control system are met. These inherent limitations include the realities that judgments in decision-making can be faulty,and that breakdowns can occur because of simple error or mistake. Additionally, controls can be circumvented by the individual acts of some persons, bycollusion of two or more people or by an unauthorized override of the controls. Accordingly, because of the inherent limitations in our control system,misstatements or insufficient disclosures due to error or fraud may occur and not be detected.Because we do not anticipate paying any cash dividends on our common stock in the foreseeable future, capital appreciation, if any, will be ourstockholders’ sole source of gain.We have never declared or paid cash dividends on our common stock. We currently intend to retain all of our future earnings, if any, to finance the growthand development of our business. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain.If securities or industry analysts do not publish research or publish inaccurate or unfavorable research about our business, our stock price and tradingvolume could decline.100Table of ContentsThe trading market for shares of our common stock depends in part on the research and reports that securities or industry analysts publish about us or ourbusiness. Although we have obtained analyst coverage, if one or more of the analysts who cover us downgrade shares of our common stock or publishinaccurate or unfavorable research about our business, our stock price would likely decline. If one or more of these analysts cease coverage of our company orfail to publish reports on us regularly, demand for our stock could decrease, which might cause our stock price and trading volume to decline.Item 1B.Unresolved Staff Comments.Not applicable.Item 2.Properties.Our manufacturing facility is located in Winnipeg, Manitoba, Canada, which we operate under a five-year renewable lease through September 2020 with aright to renew the lease for one subsequent five-year term. The manufacturing facility consists of an approximately 31,100 square foot manufacturing,laboratory, warehouse and office facility. Our U.S. corporate headquarters is located in Cambridge, MA, where we occupy office space under a lease that wasexecuted in October 2016. The initial term of the lease expired in July 2017, with the lease now continuing on a month-to-month basis unless terminated byeither party with the requisite notice. We also have office space in Philadelphia, PA, where we occupy office space under a lease that was executed inDecember 2017 and had an initial term of six months and has been extended through August 2019. We also have office space in Toronto, Ontario, Canada,where we occupy office space under a lease that is on a month-to-month basis unless terminated by either party with the requisite notice. We provided noticeof termination of the Toronto, Ontario, Canada lease in December 2018 with an effective termination date of December 31, 2018. We believe that our existingfacilities are adequate to meet our current needs, and that suitable additional alternative spaces will be available in the future on commercially reasonableterms.Item 3.Legal Proceedings.We are not currently subject to any material legal proceedings.Item 4.Mine Safety Disclosures.Not applicable.101Table of ContentsPART II Item 5.Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.Our common stock trades on the Nasdaq Global Market under the symbol “SESN”.As of February 27, 2019, we had 33 holders of record of our common stock. This number does not include beneficial owners whose shares were held in streetname.We currently intend to retain future earnings to fund the development and growth of our business. We do not expect to pay any cash dividends in theforeseeable future.Recent Sales of Unregistered SecuritiesDuring the fiscal year ended December 31, 2018, we had no sales of unregistered securities that have not been previously disclosed in a Current Report onForm 8-K or Quarterly Report on Form 10-Q.Purchase of Equity SecuritiesWe did not purchase any of our registered equity securities during the period covered by this Annual Report on Form 10-K.102Table of ContentsItem 6.Selected Financial Data.We are a smaller reporting company as defined by Rule 12b-2 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, and are not requiredto provide the information under this item.Item 7.Management’s Discussion and Analysis of Financial Condition and Results of Operations.The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our consolidated financialstatements and the notes to those financial statements appearing in this Annual Report on Form 10-K. This discussion contains forward-looking statementsthat involve risks and uncertainties. As a result of many factors, including those factors set forth in Part I, Item IA, “Risk Factors” of this Annual Report onForm 10-K, our actual results could differ materially from the results described in or implied by the forward-looking statements.OverviewWe are a late-stage clinical company developing targeted fusion protein therapeutics, or TFPTs, composed of an anti-cancer antibody fragment tethered to aprotein toxin for the treatment of cancer. We genetically fuse the cancer-targeting antibody fragment and the cytotoxic protein payload into a singlemolecule which is produced through our proprietary one-step manufacturing process. We target tumor cell surface antigens with limited expression on normalcells. Binding of the target antigen by the TFPT allows for rapid internalization into the targeted cancer cell. We have designed our targeted proteins toovercome the fundamental efficacy and safety challenges inherent in existing antibody-drug conjugates, or ADCs, where a payload is chemically attached toa targeting antibody.Our most advanced product candidate VB4-845, also known as Vicinium®, is a locally-administered targeted fusion protein composed of an anti-EPCAM, orepithelial cell adhesion molecule, antibody fragment tethered to a truncated form of Pseudomonas exotoxin A for the treatment of high-risk non-muscleinvasive bladder cancer, or NMIBC.On January 3, 2019, we reported preliminary efficacy data for the primary endpoint of our ongoing single-arm, multi-center, open-label Phase 3 clinical trialof Vicinium as a monotherapy in patients with high-risk, bacillus Calmette-Guérin, or BCG, unresponsive NMIBC, called the VISTA Trial. The data reportedthe preliminary complete response rates in evaluable Carcinoma in situ, or CIS, patients following three, six, nine and 12 months of treatment in the clinicaltrial. The results were consistent with the results observed in the previously completed Phase 1 and Phase 2 clinical trials. We expect to report updated 12-month topline efficacy and safety data during the second quarter of 2019. In August 2018, we received Fast Track designation from the FDA for Vicinium forthe treatment of high-risk NMIBC.In June 2017, we entered into a Cooperative Research and Development Agreement, or CRADA, with the National Cancer Institute, or NCI, for thedevelopment of Vicinium in combination with AstraZeneca’s immune checkpoint inhibitor, durvalumab, for the treatment of NMIBC. Under the terms of theCRADA, the NCI will conduct a Phase 1 clinical trial in patients with high-risk NMIBC to evaluate the safety, efficacy and biological correlates of Viciniumin combination with durvalumab. This Phase 1 clinical trial is open and is actively recruiting patients.Vicinium has also been evaluated for the treatment of squamous cell carcinoma of the head and neck, or SCCHN. Vicinium for the treatment of SCCHN hadpreviously been designated as Proxinium™ to indicate its different fill volume and vial size as well as its different route for local administration viaintratumoral injection.In addition to our locally-administered TFPTs, our pipeline also includes systemically-administered TFPTs in development that are built around ourproprietary de-immunized variant of the plant-derived cytotoxin bouganin, or deBouganin.We have deferred further development of Vicinium for the treatment of SCCHN and VB6-845d in order to focus our efforts and our resources on our ongoingdevelopment of Vicinium for the treatment of high-risk NMIBC. We are also exploring collaboration agreements for Vicinium for the treatment of SCCHNand VB6-845d.We were incorporated and commenced active operations in early 2008, and our operations to date have been limited to organizing and staffing our company,acquiring rights to intellectual property, business planning, raising capital, developing our technology, identifying potential product candidates,undertaking pre-clinical studies and conducting clinical trials. To date, we have financed our operations primarily through private placements of ourcommon stock and preferred stock and convertible bridge notes, venture debt borrowings, our IPO, and secondary offerings, sales effected in an “at-the-market” facility through our agent, Cowen and Company, LLC, or Cowen, from the License Agreement with Roche, and, to a lesser extent, from our formercollaboration agreement with ThromboGenics N.V., or ThromboGenics. We have devoted substantially all of our103Table of Contentsfinancial resources and efforts to research and development activities. We have not completed development of any of our product candidates. We expect tocontinue to incur significant expenses and operating losses over the next several years. Our net losses may fluctuate significantly from quarter to quarter andyear to year.We maintain global development, marketing and commercialization rights for all of our TFPT-based product candidates. Upon regulatory approval for ourproduct candidates, we will explore various commercialization strategies to market our products. If we obtain regulatory approval for Vicinium for thetreatment of high-risk NMIBC, we may build a North American specialty urology sales force to market the product or seek commercialization partners. If weobtain regulatory approval for our other product candidates, including or for Vicinium in other oncology indications, we may seek partners with oncologyexpertise in order to maximize the commercial value of each asset or a portfolio of assets. We also own or exclusively license worldwide intellectual propertyrights for all of our TFPT-based product candidates, covering our key patents with protection ranging from 2018 to 2036.License Agreement with RocheOn June 10, 2016, we entered into the License Agreement with Roche. Under the License Agreement, we granted Roche an exclusive, worldwide license todevelop and commercialize, our monoclonal antibody EBI-031 and all other IL-6 antagonist antibody technology owned by us, and pursuing ongoing patentprosecution, at its cost.Roche paid an upfront license fee of $7.5 million and a development milestone payment of $22.5 million as a result of the IND application for EBI-031becoming effective. Roche has also agreed to pay up to an additional $240.0 million upon the achievement of specified regulatory, development andcommercial milestones. In addition, we are entitled to receive royalty payments in accordance with a tiered royalty rate scale, with rates ranging from 7.5% to15% for net sales of potential future products containing EBI-031 and up to 50% of these rates for net sales of potential future products containing other IL-6compounds, with each of the royalties subject to reduction under certain circumstances and to the buy-out options of Roche.LiquiditySince inception, we have incurred significant operating losses and expect to continue to incur operating losses for the foreseeable future. We had a net loss of$33.7 million for the year ended December 31, 2018 and a net loss of $29.0 million for the year ended December 31, 2017. For the year ended December 31,2016, we had net income of $1.9 million due to the $29.6 million of revenue from the License Agreement. As of December 31, 2018, we had an accumulateddeficit of $186.0 million.On November 1, 2017, we raised approximately $7.0 million of net proceeds from the sale of 5,525,000 units (each unit consisting of one share of commonstock and one common warrant to purchase one share of common stock) and 4,475,000 pre-funded units (each pre-funded unit consisting of one pre-fundedwarrant to purchase one share of common stock and one common warrant to purchase one share of common stock) at a purchase price of $0.80 per unit and$0.79 per pre-funded unit, which we refer to as the November 2017 Financing. Each common warrant contained in a unit or pre-funded unit has an exerciseprice of $0.80 per share and is exercisable immediately and will expire five years from the date of issuance. Each pre-funded warrant contained in a pre-funded unit was exercisable for one share of common stock and the exercise price was $0.01 per share. As of December 31, 2017, all of the pre-fundedwarrants sold in connection with the November 2017 Financing had been exercised by the holders of such pre-funded warrants, resulting in net proceeds to usof $45,000. These proceeds, however, exclude any amounts that will be received from the exercise of the common warrants, if any.On March 23, 2018, we raised approximately $9.0 million of net proceeds from the sale of 7,968,128 shares of common stock at a purchase price of $1.13 pershare and warrants to purchase 7,968,128 shares of common stock at a purchase price of $0.125 per share. Each warrant to purchase common stock has anexercise price of $1.20 per share. Each common warrant is exercisable immediately and will expire five years from the date of issuance. We refer to thisfinancing as the “March 2018 Financing.”On June 4, 2018, we raised approximately $41.9 million of net proceeds from the sale of 25,555,556 shares of its common stock at a price of $1.80 per sharein an underwritten public offering. We refer to this financing as the “June 2018 Financing”.We do not know when, or if, we will generate any revenue from the sale of our product candidates as we seek regulatory approval for, and potentially begin tocommercialize, any of our product candidates. We anticipate that we will continue to incur losses for the next several years, and we expect the losses toincrease as we continue the development of, and seek regulatory approvals for, our product candidates, and begin to commercialize any approved products.We are subject to all of the risks common to the development of new products, and we may encounter unforeseen expenses, difficulties, complications, delaysand other unknown factors that may adversely affect our business. Until we can generate substantial revenue from104Table of Contentscommercial sales, if ever, we expect to seek additional capital through a combination of private and public equity offerings, debt financings, strategiccollaborations and alliances and licensing arrangements. To the extent that we raise additional capital through the sale of equity or convertible debtsecurities, the ownership interests of existing shareholders will be diluted, and the terms may include liquidation or other preferences that adversely affect therights of existing shareholders. Debt financing, if available, may involve agreements that include liens or other restrictive covenants limiting our ability totake important actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise additional funds through strategiccollaborations and alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies or grant licenses onterms that are not favorable to us. If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate ourdevelopment or commercialization efforts or grant rights to develop and market our technologies that we would otherwise prefer to develop and marketourselves.Our future capital requirements will depend on many factors, including:•the scope, initiation, progress, timing, costs and results of pre-clinical development and laboratory testing and clinical trials for our productcandidates;•our ability to establish collaborations on favorable terms, if at all, particularly manufacturing, marketing and distribution arrangements for ourproduct candidates;•the costs and timing of the implementation of commercial-scale manufacturing activities, including those associated with the manufacturing processand technology transfer to third party manufacturers to facilitate such commercial-scale manufacturing;•the costs and timing of establishing sales, marketing and distribution capabilities for our product candidates for which we may receive regulatoryapproval;•the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights anddefending any intellectual property-related claims;•our obligation to make milestone, royalty and other payments to third-party licensors under our licensing agreements;•the extent to which we in-license or acquire rights to other products, product candidates or technologies;•the outcome, timing and cost of regulatory review by the FDA and comparable foreign regulatory authorities, including the potential for the FDA orcomparable foreign regulatory authorities, including Health Canada, to require that we perform more studies or clinical trials than those that wecurrently expect;•our ability to achieve certain future regulatory, development and commercialization milestones under the License Agreement with Roche;•the effect of competing technological and market developments; and•the revenue, if any, received from commercial sales of any product candidates for which we receive regulatory approval.Accordingly, until such time that we can generate substantial revenue from product sales, if ever, we expect to finance our operations through public orprivate equity or debt financings or other sources. However, we may be unable to raise additional funds or enter into such arrangements when needed onfavorable terms, or at all, which would have a negative impact on our financial condition and could force us to delay, limit, reduce or terminate ourdevelopment programs or commercialization efforts or grant to others rights to develop or market product candidates that we would otherwise prefer todevelop and market ourselves. Failure to receive additional funding could cause us to cease operations, in part or in full. Furthermore, even if we believe wehave sufficient funds for our current or future operating plans, we may seek additional capital due to favorable market conditions or strategic considerations.We believe that our cash and cash equivalents of $50.4 million as of December 31, 2018 will be sufficient to fund our current operating plan into 2020;however, we have based this estimate on assumptions that may prove to be wrong, and our capital resources may be utilized faster than we currently expect.Financial Operations OverviewRevenueTo date, we have not generated any revenues from the sale of products. Substantially all of our revenue to date has been derived from the License Agreementwith Roche and, to a lesser extent, from our former collaboration with ThromboGenics. We do not105Table of Contentsexpect to generate significant product revenue unless and until we obtain marketing approval for, and commercialize our product candidates.Under the terms of the License Agreement with Roche, Roche paid an upfront license fee of $7.5 million and a development milestone payment of $22.5million as a result of the IND application for EBI-031 becoming effective.We are also entitled to receive up to an additional $240.0 million upon theachievement of other specified regulatory, development and commercial milestones, as well as royalties based on net sales of potential future productscontaining EBI-031 or any other potential future products containing other IL-6 compounds. The next licensing milestone payment expected from Roche, ifany, will be triggered upon commencement of a Phase 2 clinical trial.Under the collaboration and license agreement with ThromboGenics, which we entered into in May 2013, we and ThromboGenics collaborated to seek toidentify protein or peptide therapeutics that directly modulate any of a specified set of targets in a novel pathway in retinal disease. In connection with theagreement, ThromboGenics paid us an upfront technology licensing fee of $1.75 million and paid us to perform activities under the agreement at a set rateper full-time equivalent person working on collaboration activities. On August 1, 2016, we received notice from ThromboGenics of ThromboGenics’stermination, effective as of October 31, 2016, of the agreement.Research and Development ExpensesResearch and development expenses consist primarily of costs incurred for the development of our product candidates, which include: •employee-related expenses, including salaries, benefits, travel and stock-based compensation expense;•expenses incurred under agreements with CROs, and investigative sites that conduct our clinical trials;•expenses associated with developing manufacturing capabilities and manufacturing clinical study materials;•facilities, depreciation, and other expenses, which include direct and allocated expenses for rent and maintenance of facilities, insurance, and othersupplies; and•expenses associated with pre-clinical and regulatory activities.We expense research and development costs as incurred. We recognize external development costs based on an evaluation of the progress to completion ofspecific tasks using information and data provided to us by our vendors and our clinical sites.The successful development and commercialization of any product candidate is highly uncertain. This is due to the numerous risks and uncertaintiesassociated with product development and commercialization, including the uncertainty of:•the scope, progress, outcome and costs of our clinical trials and other research and development activities;•the efficacy and potential advantages of our product candidates compared to alternative treatments, including any standard of care;•the market acceptance of our product candidates;•the cost and timing of the implementation of commercial-scale manufacturing of our product candidates;•obtaining, maintaining, defending and enforcing patent claims and other intellectual property rights;•significant and changing government regulation; and•the timing, receipt and terms of any marketing approvals.A change in the outcome of any of these variables with respect to the development of any product candidate could mean a significant change in the costs andtiming associated with the development of that product candidate. For example, if the FDA or another regulatory authority were to require us to conductclinical trials or other testing beyond those that we currently contemplate will be required for the completion of clinical development of any productcandidate, or if we experience significant delays in enrollment in any of our clinical trials, we could be required to expend significant additional financialresources and time on the completion of clinical development of that product candidate.We allocate direct research and development expenses, consisting principally of external costs, such as fees paid to investigators, consultants, centrallaboratories and CROs in connection with our clinical trials, and costs related to manufacturing or purchasing clinical trial materials, to specific productprograms. We do not allocate employee and contractor-related costs, costs associated with our platform and facility expenses, including depreciation or otherindirect costs, to specific106Table of Contentsproduct programs because these costs are deployed across multiple product programs under research and development and, as such, are separately classified.The table below provides research and development expenses incurred for our Vicinium, VB6-845d, EBI-031 and isunakinra product programs and otherexpenses by category. Based on negative results for our completed Phase 3 clinical trials in dry eye disease and allergic conjunctivitis, we are no longerdeveloping isunakinra. We have deferred further development of Vicinium for the treatment of SCCHN and VB6-845d in order to focus our efforts and ourresources on our ongoing development of Vicinium for the treatment of high-risk NMIBC. Since the acquisition of Viventia, our research and developmentexpenses have been related primarily to the development of Vicinium for the treatment of high-risk NMIBC. We expect our research and developmentexpenses for Vicinium will continue to increase during subsequent periods. We did not allocate research and development expenses to any other specificproduct programs during the periods presented: Year ended December 31, 20182017 2016* (in thousands)Programs: Vicinium for the treatment of high-risk NMIBC (1)$8,942$6,974 $1,564 Vicinium for the treatment of SCCHN (2)$—— —VB6-845d (2)$—— —EBI-031 (3)—— 2,996Isunakinra/EBI-005 (4)—— 1,653Total direct program expenses8,9426,974 6,213Personnel and other expenses: Employee and contractor-related expenses3,9133,871 5,863Platform-related lab expenses250455 479Facility expenses363398 561Other expenses609812 363Total personnel and other expenses5,1355,536 7,266Total research and development expenses$14,077$12,510 $13,479(1) We expect our development activities for Vicinium will increase significantly during subsequent periods.(2) We have deferred further development of Vicinium for the treatment of SCCHN and VB6-845d in order to focus our efforts and our resources on ourongoing development of Vicinium for the treatment of high-risk NMIBC.(3) Beginning August 16, 2016, Roche is responsible for all development costs for EBI-031.(4) Our development activities for isunakinra are no longer ongoing as of December 31, 2016.* Includes Viventia related expenses since September 20, 2016.General and Administrative ExpensesGeneral and administrative expenses consist primarily of salaries and related costs for personnel, including stock-based compensation, in executive,operational, finance, business development and human resource functions. Other general and administrative expenses include facility-related costs andprofessional fees for legal, patent, consulting and accounting services.Changes in Fair Value of Contingent ConsiderationIn connection with the acquisition of Viventia, we recorded contingent consideration pertaining to the amounts potentially payable to Viventia'sshareholders pursuant to the terms of the share purchase agreement. The fair value of contingent consideration is assessed at each balance sheet date andchanges, if any, to the fair value are recognized within the consolidated statements of operations and comprehensive income (loss).Other Income (Expense), NetOther income and expense consists primarily of interest income earned on cash and cash equivalents, interest expense on outstanding debt, the gain or lossassociated with the change in the fair value of our common stock warrant liability that are carried at fair value, the loss on extinguishment of debt.Critical Accounting Policies and Significant Judgments and Estimates107Table of ContentsThis management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which wehave prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of these financial statements requires us to makeestimates and judgments that affect the reported amounts of assets, liabilities, and expenses and the disclosure of contingent assets and liabilities in ourfinancial statements. On an ongoing basis, we evaluate our estimates and judgments, including those related to revenue recognition, accrued research anddevelopment expenses, stock-based compensation, fair value of warrants to purchase common stock, fair value of intangible assets and goodwill, incometaxes including the valuation allowance for deferred tax assets, contingent consideration and going concern considerations. We base our estimates onhistorical experience, known trends and events and various other factors that we believe are reasonable under the circumstances, the results of which form thebasis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ fromthese estimates under different assumptions or conditions.While our significant accounting policies are described in more detail in the notes to our audited consolidated financial statements appearing elsewhere inthis Annual Report on Form 10-K, we believe the following accounting policies to be most critical to the judgments and estimates used in the preparation ofour financial statements.Revenue RecognitionTo date, we have not generated any revenue from the sale of products. Substantially all of our revenue to date has been derived from the License Agreementwith Roche and, to a lesser extent, from our former collaboration with ThromboGenics N.V., or ThromboGenics. We do not expect to generate significantproduct revenue unless and until we obtain marketing approval for and commercialize our product candidates.On June 10, 2016, we entered into the License Agreement with Roche, which became effective on August 16, 2016. Under the License Agreement, we grantedRoche an exclusive, worldwide license, including the right to sublicense, to its patent rights and know-how related to our monoclonal antibody EBI-031 orany other IL-6 antagonist anti-IL-6 monoclonal antibody, to make, have made, use, have used, register, have registered, sell, have sold, offer for sale, importand export any product containing such an antibody or any companion diagnostic used to predict or monitor response to treatment with such a product,which we collectively refer to as the Licensed Intellectual Property.During 2016, we received an upfront license fee of $7.5 million and a milestone payment of $22.5 million. We are entitled to receive up to $240.0 million inadditional consideration upon the achievement of specified regulatory, development and commercial milestones. Specifically, an aggregate amount of up to$175.0 million is payable to us for the achievement of specified milestones with respect to the first indication: $50.0 million in development milestones,$50.0 million in regulatory milestones and $75.0 million in commercialization milestones. Additional amounts of up to $65.0 million are payable upon theachievement of specified development and regulatory milestones in a second indication. In addition, we are entitled to receive royalty payments inaccordance with a tiered royalty rate scale, with rates ranging from 7.5% to 15% for net sales of potential future products containing EBI-031 and up to 50%of these rates for net sales of potential future products containing other IL-6 compounds, with each of the royalties subject to reduction under certaincircumstances and to buy-out options.In May 2014, the Financial Accounting Standards Board ("FASB") issued Accounting Standards Update ("ASU") No. 2014-09, codified as AccountingStandards Codification ("ASC") 606, Revenue from Contracts with Customers ("ASC 606"), which supersedes all existing revenue recognition requirements,including most industry-specific guidance. The License Agreement is subject to the provisions of ASC 606, which was adopted effective January 1, 2018utilizing a modified retrospective method. We concluded that all performance obligations had been achieved as of the adoption date and therefore the fulltransaction price was considered earned. The transaction price was determined to be the $30.0 million received in 2016. Additional consideration to be paidto us upon the achievement of certain milestones will be included if it is expected that the amounts will be received and the amounts would not be subject toa constraint. As of the date of the adoption, no amounts were expected to be received from the achievement of any milestones due to the nature of themilestones and the development status of the product candidates at the time of the adoption. As a result, there were no amounts required to be recorded as acumulative adoption adjustment as the consideration recognized under ASC 606 was consistent with the amounts recognized under the previous accountingliterature.As of December 31, 2018, we concluded that there would be no adjustments to the transaction price as we continue to not expect any amounts to be receivedfrom any milestones within the License Agreement. This is due to the nature of the milestones and the development status of the product candidates at thetime of the adoption. As a result, no revenue was recognized during the twelve month period ended December 31, 2018 as all performance obligations hadbeen previously achieved and there was no change in the transaction price during the period. No revenue would have been recognized under108Table of Contentsthe previous accounting literature during the year ended December 31, 2018 as no milestones were achieved in the period, which was the revenue recognitioncriteria under the previous accounting literature.Accrued Research and Development ExpensesAs part of the process of preparing our consolidated financial statements, we are required to estimate our accrued expenses. This process involves reviewingquotes and contracts, identifying services that have been performed on our behalf and estimating the level of service performed and the associated costincurred for the service when we have not yet been invoiced or otherwise notified of the actual cost. The majority of our service providers invoice us monthlyin arrears for services performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date in ourfinancial statements based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with the serviceproviders and make adjustments if necessary. The significant estimates in our accrued research and development expenses are related to fees paid to CROsand CMOs and other vendors in connection with research and development activities for which we have not yet been invoiced.We base our expenses related to CROs and CMOs on our estimates of the services received and efforts expended pursuant to quotes and contracts with CROsand CMOs that conduct research and development on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract tocontract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services providedand result in a prepayment of the research and development expense. In accruing service fees, we estimate the time period over which services will beperformed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from ourestimate, we adjust the accrual or prepayment expense accordingly. Although we do not expect our estimates to be materially different from amounts actuallyincurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and couldresult in our reporting amounts that are too high or too low in any particular period. There have been no material changes in estimates for the periodspresented.Stock-based CompensationWe account for all stock-based compensation payments to employees, directors and non-employees using an option pricing model for estimating fair value.Accordingly, stock-based compensation expense is measured based on the estimated fair value of the awards on the date of grant, and prior to January 1,2017, net of estimated forfeitures. We recognize stock-based compensation expense over the period during which the recipient renders the required servicesto us using the straight-line method. In accordance with authoritative guidance, we remeasure the fair value of non-employee stock-based awards as theawards vest, and recognize the resulting value, if any, as expense during the period the related services are rendered (A).(A) For awards with performance conditions, we recognize expense when the condition is probable of achievement, over the implied service period of theaward.Significant Factors, Assumptions and Methodologies Used in Determining Fair ValueWe apply the fair value recognition provisions of ASC Topic 718, Compensation-Stock Compensation, or ASC 718. Determining the amount of stock-basedcompensation to be recorded requires us to develop estimates of the fair value of stock options as of their grant date. We recognize stock-based compensationexpense for service-based awards ratably over the requisite service period, which in most cases is the vesting period of the award. Calculating the fair value ofstock-based awards requires that we make subjective assumptions.We use the Black-Scholes option pricing model to value our stock option awards. Use of this valuation methodology requires that we make assumptions as tothe volatility of our common stock, the expected term of our stock options, the risk free interest rate for a period that approximates the expected term of ourstock options and our expected dividend yield. As we have only been a public company since December 2014, we do not have sufficient history to estimatethe volatility of our common stock price or the expected life of the options. We calculate expected volatility based on reported data for similar publiclytraded companies for which historical information is available and will continue to do so until the historical volatility of our common stock is sufficient tomeasure expected volatility for future option grants. During the periods we were a privately held company with a limited operating history, we utilized datafrom a representative group of public companies to estimate expected stock price volatility. We selected companies from the biopharmaceutical industry withsimilar characteristics to us, including those at a similar stage of development and with a similar therapeutic focus.We use the “simplified method” to estimate the expected term of stock option grants to employees. Under this approach, the weighted-average expected lifeis presumed to be the average of the contractual term (ten years) and the vesting term (generally109Table of Contentsfour years) of our stock options, taking into consideration multiple vesting tranches. We utilize this method due to a lack of historical exercise data. We havenever paid, and do not anticipate paying, any cash dividends in the foreseeable future, and therefore use an expected dividend yield of zero in the option-pricing model. The risk-free rate is based on the yield curve of U.S. Treasury securities with periods commensurate with the expected term of the optionsbeing valued. The fair value of each stock option granted to employees and directors is estimated on the date of grant using the Black-Scholes option-pricingmodel based on the assumptions noted in the following table: Year Ended December 31, 2018 2017 2016Risk-free interest rate2.47 - 2.97% 1.88 - 2.04% 1.23 - 2.38%Expected dividend yield—% —% —%Expected term (in years)5.75 - 6 5.3 - 6 5.5 - 6Expected volatility73.61 - 78.28% 75.4 - 86.66% 71.44 - 92.09%Prior to January 1, 2017, we were required to estimate forfeitures at the time of grant and revise those estimates in subsequent periods if actual forfeituresdiffer from our estimates. We used historical data to estimate pre-vesting option forfeitures and record stock-based compensation expense only for thoseawards that were expected to vest. To the extent that actual forfeitures differed from our estimates, the difference was recorded as a cumulative adjustment inthe period the estimates were revised. Stock-based compensation expense recognized in the financial statements is based on awards that ultimately vest.Business CombinationsOn September 20, 2016, we completed our acquisition of Viventia for total consideration of $45.1 million, consisting of common stock consideration of$13.5 million and contingent consideration with a fair value of $31.6 million. Future changes in our estimates of contingent consideration may impactresearch and development expense in future periods. The estimated fair value of the contingent consideration is based upon significant assumptionsregarding probabilities of successful achievement of related milestones, the estimated timing in which the milestones are achieved and discount rates. Theestimated fair value could materially differ from actual values or fair values determined using different assumptions.This transaction was accounted for as a business combination under the purchase method of accounting. Accordingly, the tangible assets and identifiableintangible assets acquired and liabilities assumed were recorded at fair value as of the date of acquisition, with the remaining purchase price recorded asgoodwill. The estimated fair values of acquired assets and assumed liabilities were determined using the methods discussed in the following paragraphs andrequire significant judgment and estimates, which could materially differ from actual values and fair values determined using different methods orassumptions.The purchase accounting for our acquisition of Viventia was finalized during the third quarter of 2017. We valued the acquired assets and liabilities based ontheir estimated fair values as of September 20, 2016, or the Acquisition Date. The final allocation of the purchase consideration was updated from thepreliminary amounts to reflect new information related to facts and circumstances which existed as of the Acquisition Date. The changes in assumptions wereprimarily due to additional information gathered regarding the potential market for Vicinium outside of the U.S., which resulted in adjustments to the fairvalue of contingent consideration as of the Acquisition Date and the in-process research and development assets for Vicinium in the E.U. and the rest ofworld. The assumptions related to the U.S. market were not updated as sufficient information had previously been gathered to support this estimate. Theupdate of these assumptions also had an effect on the discount rate and certain other valuation assumptions used to value the acquired assets due to anadjustment in our specific risk factors, which effected the in-process research and development assets for Vicinium in the U.S., E.U., and the rest of world. As aresult of these changes, we updated (1) the fair value of the in-process research and development assets for Vicinium, which resulted in a reduction in the fairvalue of the in-process research and development asset for Vicinium in the rest of the world to a di minimus amount, (2) the fair value of the contingentconsideration, and (3) the related deferred tax liability and goodwill.GoodwillGoodwill represents the difference between the purchase price and the fair value of the identifiable tangible and intangible net assets when accounted forusing the purchase method of accounting. Goodwill is not amortized, but is reviewed for impairment. We test our goodwill for impairment annually, orwhenever events or changes in circumstances indicate an impairment may have occurred, by comparing its carrying value to its implied fair value inaccordance with ASC Topic 350, Intangibles - Goodwill and Other, or ASC 350. Impairment may result from, among other things, deterioration in theperformance of the acquired asset, adverse market conditions, adverse changes in applicable laws or regulations and a variety of other circumstances. If wedetermine that an impairment has occurred, a write-down of the carrying value and an impairment110Table of Contentscharge to operating expenses in the period the determination is made is recorded. In evaluating the carrying value of goodwill, we must make assumptionsregarding estimated future cash flows and other factors to determine the fair value of the reporting unit. Changes in strategy or market conditions couldsignificantly impact those judgments in the future and require an adjustment to the recorded balance. We have not recognized any impairment chargesrelated to goodwill.Indefinite-Lived Intangible AssetsIn accordance with ASC 350, during the period that an asset is considered indefinite-lived, such as in-process research and development, or IPR&D, it will notbe amortized. Acquired IPR&D represents the fair value assigned to research and development assets that have not reached technological feasibility. Thevalue assigned to acquired IPR&D is determined by estimating the costs to develop the acquired technology into commercially viable products, estimatingthe resulting revenue from the projects, and discounting the net cash flows to present value. The revenue and costs projections used to value acquired IPR&Dare, as applicable, reduced based on the probability of success of developing a new drug. Additionally, the projections consider the relevant market sizes andgrowth factors, expected trends in technology, and the nature and expected timing of new product introductions by us and our competitors. The rates utilizedto discount the net cash flows to their present value are commensurate with the stage of development of the projects and uncertainties in the economicestimates used in the projections. Upon the acquisition of IPR&D, we complete an assessment of whether its acquisition constitutes the purchase of a singleasset or a group of assets. Multiple factors are considered in this assessment, including the nature of the technology acquired, the presence or absence ofseparate cash flows, the development process and stage of completion, quantitative significance and the rationale for entering into the transaction. Indefinite-lived assets are maintained on our consolidated balance sheet until either the project underlying it is completed or the asset becomes impaired. Indefinite-lived assets are tested for impairment on an annual basis, or whenever events or changes in circumstances indicate the reduction in the fair value of theIPR&D asset is below its respective carrying amount. If we determine that an impairment has occurred, a write-down of the carrying value and an impairmentcharge to operating expenses in the period the determination is made is recorded. When development of an IPR&D asset is complete the associated assetwould be deemed finite-lived and would then be amortized based on its respective estimated useful life at that point.Contingent ConsiderationEach reporting period, we revalue the contingent consideration obligations associated with business combinations to their fair value and record increases intheir fair value as contingent consideration expense and decreases in the fair value as contingent consideration income. Changes in contingent considerationresult from changes in the assumptions regarding probabilities of successful achievement of regulatory milestones and commercial sales, the period in whichthese milestones and sales are expected to be achieved, the level of commercial sales of Vicinium, and discount rates used to estimate the fair value of theliability. Significant changes in any of these assumptions would result in a significantly higher or lower fair value measurement.Recently Issued Accounting PronouncementsSee Note 2 within the notes to our audited consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K for a discussion onrecently issued accounting pronouncements.Emerging Growth Company StatusThe JOBS Act permits an “emerging growth company” such as us to take advantage of an extended transition period to comply with new or revisedaccounting standards applicable to public companies until those standards would otherwise apply to private companies. We have irrevocably elected to “optout” of this provision and, as a result, we will comply with new or revised accounting standards as required when they are adopted.Results of OperationsComparison of the Years Ended December 31, 2018 and 2017111Table of Contents Year endedDecember 31, 2018 2017 Change (in thousands)Revenue: Collaboration revenue$— $— $—License revenue— 425 (425)Total revenue— 425 (425)Operating expenses: Research and development14,077 12,510 1,567General and administrative11,623 8,070 3,553Loss from change in fair value of contingent consideration8,800 9,100 (300)Total operating expenses34,500 29,680 4,820(Loss) from operations(34,500) (29,255) (5,245)Other income, net807 226 581Net (loss) before income taxes(33,693) (29,029) (4,664)Provision for income taxes— — —Net (loss) and comprehensive (loss)$(33,693) $(29,029) $(4,664)Revenue. Revenue was $0.0 million for the year ended December 31, 2018 compared to $0.4 million for the year ended December 31, 2017. The decrease wasdue to a decrease in license revenue we recognized in 2017 pursuant to the License Agreement with Roche.Research and development expenses. Research and development expenses were $14.1 million for the year ended December 31, 2018 compared to $12.5million for the year ended December 31, 2017. The increase of $1.6 million was due primarily to increases in tech transfer and commercial manufacturingcosts of $2.5 million and $0.6 million higher consulting fees in support of the VISTA Trial. These increases were partially offset by decreases in ViciniumCRO-related development expenses of $1.3 million and a reduction in materials/lab supplies of $0.2 million as internal manufacturing costs were replaced byexternal technology transfer costs.General and administrative expenses. General and administrative expenses were $11.6 million for the year ended December 31, 2018 compared to $8.1million for the year ended December 31, 2017. The increase of $3.6 million was due primarily to an increase of professional and legal fees of $1.8 million aswell as severance and relocation costs of $0.9 million related to our CEO transition. In addition, the company increased commercial market research costs by$0.6 million for the year ended December 31, 2018.Loss from change in fair value of contingent consideration. The change in loss in fair value of contingent consideration was $0.3 million for the year endedDecember 31, 2018 compared to the year ended December 31, 2017. The expense in both years was due primarily to changes in the discount rates andassumptions related to development and commercialization timelines and estimated sales projections.Other income, net. Other income, net was $0.8 million for the year ended December 31, 2018 compared to $0.2 million for the year ended December 31,2017. The change of $0.6 million was due primarily to the increase in interest income on higher cash balances due to recent equity financings.Comparison of the Years Ended December 31, 2017 and 2016112Table of Contents Year endedDecember 31, 2017 2016 Change (in thousands) Revenue: Collaboration revenue$— $406 $(406)License revenue425 29,575 $(29,150)Total revenue425 29,981 (29,556)Operating expenses: Research and development12,510 13,479 (969)General and administrative8,070 14,736 (6,666)Loss (gain) from change in fair value of contingent consideration9,100 (1,100) 10,200Total operating expenses29,680 27,115 2,565(Loss) income from operations(29,255) 2,866 (32,121)Other income (expense), net226 (970) 1,196Net (loss) income before income taxes(29,029) 1,896 (30,925)Provision for income taxes— 5 (5)Net (loss) income and comprehensive (loss) income(29,029) $1,891 $(30,920)Revenue. Revenue was $0.4 million for the year ended December 31, 2017 compared to $30.0 million for the year ended December 31, 2016. The decreasewas due primarily to a decrease in license revenue as we recognized the upfront license fee and development milestone payment under the LicenseAgreement with Roche, relating to the execution of the License Agreement and the successful submission of the IND application for EBI-031, as well as adecrease in collaboration revenue from our terminated collaboration with ThromboGenics. This decrease was offset partially by revenue recognized under theLicense Agreement with Roche for the year ended December 31, 2017 relating to the transfer of pre-clinical inventory to Roche.Research and development expenses. Research and development expenses were $12.5 million for the year ended December 31, 2017 compared to $13.5million for the year ended December 31, 2016. The decrease of $1.0 million was due primarily to a decrease in EBI-031 related development expenses of $3.0million due to the License Agreement with Roche in which Roche is responsible for all on-going development expenses, as well as a decrease of $1.7 millionof isunakinra-related development expenses, which development activities are no longer ongoing. These decreases were partially offset by increases inVicinium related development expenses since the Acquisition Date of $5.4 million. In addition, employee and contractor-related expenses, including stock-based compensation and severance, were $3.9 million for the year ended December 31, 2017 compared to $5.9 million for the year ended December 31, 2016.General and administrative expenses. General and administrative expenses were $8.1 million for the year ended December 31, 2017 compared to $14.7million for the year ended December 31, 2016. The decrease of $6.7 million was due primarily to a reduction of professional fees as well as salaries andrelated costs for personnel, including stock-based compensation. For the year ended December 31, 2016, we had higher professional fees related to theLicense Agreement with Roche, our 2016 review of strategic alternatives and the acquisition of Viventia. In addition, for the year ended December 31, 2016,we had higher severance costs related to the acquisition of Viventia.Loss (gain) from change in fair value of contingent consideration. The change in fair value of contingent consideration was $10.2 million for the year endedDecember 31, 2017 compared to the year ended December 31, 2016 due primarily to updates in projected revenue assumptions related to Vicinium.Other income (expense), net. Other income (expense), net was $0.2 million for the year ended December 31, 2017 compared to $(1.0) million for the yearended December 31, 2016. The change of $1.2 million was due primarily to the loss on extinguishment of debt in 2016 associated with the prepayment of theloan with Silicon Valley Bank, or SVB as well as the interest expense incurred until the loan was prepaid.Liquidity and Capital Resources113Table of ContentsSources of LiquiditySince inception, we have incurred significant operating losses and expect to continue to incur operating losses for the foreseeable future. Substantially all ofour revenue to date has been from the License Agreement and, to a lesser extent, from our former collaboration agreement with ThromboGenics. To date, wehave financed our operations primarily through private placements of our common stock, preferred stock and bridge notes convertible into our preferredstock, venture debt borrowings, our IPO and secondary offerings, sales effected in an “at-the-market” facility through our agent, Cowen, the LicenseAgreement with Roche and, to a lesser extent, from our former collaboration agreement with ThromboGenics.In June 2016, we entered into the License Agreement with Roche and received an up-front license fee of $7.5 million and up to an additional $262.5 millionupon the achievement of specified regulatory, development and commercial milestones with respect to up to two unrelated indications. Specifically, anaggregate amount of up to $197.5 million is payable to us for the achievement of specified milestones with respect to the first indication: consisting of $72.5million in development milestones, $50.0 million in regulatory milestones and $75.0 million in commercialization milestones. We received the firstdevelopment milestone payment of $22.5 million as a result of the IND for EBI-031 becoming effective. In addition, we are entitled to receive royaltypayments in accordance with a tiered royalty rate scale, with rates ranging from 7.5% to 15% for net sales of potential future products containing EBI-031and at up to 50% of these rates for net sales of potential future products containing other IL-6 compounds, with each of the royalties subject to reductionunder certain circumstances and to the buy-out options of Roche.On November 1, 2017, we raised approximately $7.0 million of net proceeds from the sale of 5,525,000 units (each unit consisting of one share of commonstock and one common warrant to purchase one share of common stock) and 4,475,000 pre‑funded units (each pre-funded unit consisting of one pre-fundedwarrant to purchase one share of common stock and one common warrant to purchase one share of common stock) at a purchase price of $0.80 per unit and$0.79 per pre-funded unit. Each common warrant contained in a unit or a pre-funded unit has an exercise price of $0.80 per share and is exercisableimmediately and will expire five years from the date of issuance. Each pre-funded warrant contained in a pre-funded unit was exercisable for one share ofcommon stock and the exercise price was $0.01 per share. As of December 31, 2017, all of the pre-funded warrants sold in connection with the November2017 Financing had been exercised by the holders of such pre-funded warrants, resulting in net proceeds to us of $45,000. In 2018, we received proceeds of$6.4 million from the issuance of 8,008,313 shares of our common stock upon the cash exercise of common stock purchase warrants issued in connectionwith this underwritten public offering.On March 23, 2018, we raised approximately $9.0 million of net proceeds from the sale of 7,968,128 shares of common stock at a purchase price of $1.13 pershare and a concurrent sale of sold warrants to purchase 7,968,128 shares of common stock at a purchase price of $0.125 per warrant. The warrants areexercisable immediately upon issuance at an exercise price equal to $1.20 per share of common stock, subject to adjustments as provided under the terms ofthe warrants. In 2018, we received proceeds of $0.9 million from the issuance of 757,183 shares of our common stock upon the cash exercise of commonstock purchase warrants issued in connection with this private placement.On June 4, 2018, we raised approximately $41.9 million of net proceeds from the sale of 25,555,556 shares of our common stock at a price of $1.80 per sharein the June 2018 Financing.Cash FlowsAs of December 31, 2018, we had cash and cash equivalents of $50.4 million. Cash in excess of immediate requirements is invested in accordance with ourinvestment policy, with a view primarily to liquidity and capital preservation.The following table sets forth the primary sources and uses of cash for each of the periods set forth below: Year ended December 31, 2018 2017 2016 (in thousands)Net cash provided by (used in): Operating activities$(22,829) (17,765) $2,622Investing activities(2) 98 461Financing activities58,583 7,005 (13,820)Net increase (decrease) in cash and cash equivalents$35,752$(10,662) $(10,737)114Table of ContentsOperating activities. Net cash used in operating activities was $22.8 million for the year ended December 31, 2018, and consisted primarily of the net loss of$33.7 million adjusted for non-cash items, including stock-based compensation expense of $1.3 million, depreciation expense of $0.2 million, a net changeof $8.8 million in the fair value of the contingent consideration and a net change in operating assets and liabilities of $0.6 million.Net cash used in operating activities was $17.8 million for the year ended December 31, 2017, and consisted primarily of the net loss of $29.0 millionadjusted for non-cash items, including stock-based compensation expense of $1.4 million, depreciation expense of $0.3 million, a net change of $9.1 millionin the fair value of the contingent consideration and a net change in operating assets and liabilities of $0.6 million.Net cash provided by operating activities was $2.6 million for the year ended December 31, 2016, and consisted primarily of net income of $1.9 millionadjusted for non-cash items, including stock-based compensation expense of $4.0 million, depreciation expense of $0.2 million, a net change of $(0.1)million in the fair value of the warrant liability, a net change of $(1.1) million in the fair value of the contingent consideration, $0.2 million loss onextinguishment of debt and a net change in operating assets and liabilities of $(2.5) million.Investing activities. Net cash provided by (used in) investing activities consists of sales and purchases of property and equipment. For the years endedDecember 31, 2018 and 2017, we had cash proceeds from the sale of property and equipment of $0.0 million and $0.1 million, respectively. For the yearended December 31, 2016, we had cash proceeds from the sale of property and equipment of $0.3 million and also acquired $0.1 million of cash from theacquisition of Viventia.Financing activities. Net cash provided by financing activities for the year ended December 31, 2018 consisted primarily of the $58.3 million proceeds fromour March and June Financings and the exercise of common stock warrants. Net cash provided by financing activities for the year ended December 31, 2017consisted of the $7.0 million proceeds from our November 2017 Financing. Net cash used in financing activities for the year ended December 31, 2016 was$13.8 million and consisted primarily of repayment of outstanding debt obligations. On March 1, 2016, we prepaid all outstanding amounts owed to SVBand terminated our loan agreement with SVB. This was partially offset by proceeds from the exercise of stock options of $0.3 million.Funding RequirementsWe will incur substantial expenses if and as we:•continue our Phase 3 clinical trial for Vicinium for the treatment of high-risk NMIBC;•continue the research and pre-clinical and clinical development of our other product candidates;•seek to discover and develop additional product candidates;•in-license or acquire the rights to other products, product candidates or technologies;•seek marketing approvals for any product candidates that successfully complete clinical trials;•establish sales, marketing and distribution capabilities and scale up and validate external manufacturing capabilities (including initiating andcompleting the manufacturing process and technology transfer to any third-party manufacturers) to commercialize any products for which we mayobtain marketing approval;•maintain, expand and protect our intellectual property portfolio;•add equipment and physical infrastructure to support our research and development;•hire additional clinical, quality control, scientific and management personnel; and•expand our operational, financial and management systems and personnel.We believe that our cash and cash equivalents of $50.4 million as of December 31, 2018 will be sufficient to fund our current operating plan into 2020;however, we have based this estimate on assumptions that may prove to be wrong, and our capital resources may be utilized faster than we currently expect.Our future capital requirements will depend on many factors, including:•the scope, initiation, progress, timing, costs and results of pre-clinical development and laboratory testing of our pre-clinical product candidates;115Table of Contents•our ability to establish collaborations on favorable terms, if at all, particularly manufacturing, marketing and distribution arrangements for ourproduct candidates;•the costs and timing of the implementation of commercial-scale manufacturing activities;•the costs and timing of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatoryapproval;•the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights anddefending any intellectual property-related claims;•our obligation to make milestone, royalty and other payments to third party licensors under our licensing agreements;•the extent to which we in-license or acquire rights to other products, product candidates or technologies;•the outcome, timing and cost of regulatory review by the FDA and comparable foreign regulatory authorities, including the potential for the FDA orcomparable foreign regulatory authorities, including Health Canada, to require that we perform more studies or clinical trials than those that wecurrently expect;•our ability to achieve certain future regulatory, development and commercialization milestones under the License Agreement with Roche;•the effect of competing technological and market developments; and•the revenue, if any, received from commercial sales of any product candidates for which we receive regulatory approval.Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debtfinancings, government or other third-party funding, collaborations, strategic alliances, licensing arrangements and marketing and distribution arrangements.We do not have any committed external source of funds other than the amounts payable under the License Agreement with Roche. To the extent that we raiseadditional capital through the sale of equity or convertible debt securities, our stockholders’ ownership interest will be diluted, and the terms of thesesecurities may include liquidation or other preferences that adversely affect our stockholders’ rights as holders of our common stock. Debt financing andequity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurringadditional debt, making capital expenditures or declaring dividends. If we raise additional funds through government or other third-party funding,collaborations, strategic alliances, licensing arrangements or marketing and distribution arrangements, we may have to relinquish valuable rights to ourtechnologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us. If we are unable toraise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development orfuture commercialization efforts or grant rights to develop and market products or product candidates that we would otherwise prefer to develop and marketourselves.Contractual Obligations and CommitmentsThe following table summarizes our contractual obligations at December 31, 2018: Total Less than 1Year (a) 1 to 3 Years 3 to 5 Years More than 5Years (in thousands)Operating lease obligations (1)$402 295 107 $— $—License maintenance fees (2)1,004 182 547 275 —Total fixed contractual obligations$1,406 $477 $654 $275 $—(a) We canceled certain leases effective March 31, 2019 and therefore no amounts have been included subsequent to that date.(1) We lease our manufacturing facility located in Winnipeg, Manitoba Canada, which consists of an approximately 31,100 square foot manufacturing,laboratory, warehouse and office facility, under a five-year renewable lease through September 2020. The monthly rent for this office space is approximately$12,400 per month. We also expect to incur approximately $13,300 in related operating expenses per month. We entered certain short term leases (twelvemonths or less) for office space in Philadelphia, PA, that has monthly rent of approximately $20,500 per month. We entered into a four-month lease for officespace in Cambridge, MA effective January 1, 2019, that has a monthly rent of approximately $10,000 per month.116Table of Contents(2) We have entered into various license agreements that, upon successful clinical development, contingently trigger payments upon achievement of certainmilestones, royalties and other such payments. See ‘‘License Agreements’’ below. Because the achievement of these milestones are uncertain, the amountshave not been included.We enter into agreements in the normal course of business with CROs for clinical trials and with vendors for pre-clinical studies, license agreements and otherservices and products for operating purposes which are cancelable by us, upon prior written notice. We have an agreement with a CRO that may be terminatedat any time with 30 days’ notice; however, upon termination, we would be required to pay all costs incurred by the CRO up to the termination date, plus anadditional fee, which is calculated as an amount equal to either (a) 5% of the unearned fees for services as provided in the budget if we have paid 50% ormore of the total fees for services as specified in the work order or (b) 3% of the amount of fees we have paid for services as of the date of termination if wehave paid less than 50% of the total fees for services as specified in the work order. As of December 31, 2018, we have been invoiced $7.1 million in fees forservices from this CRO, which is more than 50% of the total fees for services as specified in the current work order with this CRO. Therefore, as ofDecember 31, 2018, we would have been required to pay a termination fee of 5% of the amount of fees as of the date of termination of this agreement, whichwould have equaled $198,000 as of December 31, 2018. Amounts owed to such CRO were not included in the ‘‘Contractual Obligations and Commitments’’table above as it was considered a contingent payment as of December 31, 2018.We occupied office space in Toronto, Ontario, Canada with rent of approximately $2,000 per month. We provided notice of termination of this lease inDecember 2018 with an effective termination date of December 31, 2018. We also occupied space in Willow Grove, PA, under a one-year lease that wasexecuted in May 2017 and terminated in May 2018. The monthly rent for this office space is approximately $2,000 per month. These payments are notincluded in the ‘‘Contractual Obligations and Commitments’’ table above.In connection with the acquisition of Viventia, we are obligated to pay to the sellers certain post-closing contingent cash payments upon the achievement ofspecified milestones and based upon net sales, in each case subject to the terms and conditions set forth in the acquisition agreement, including: (i) a one-time milestone payment of $12.5 million payable upon the first sale of Vicinium or any variant or derivative thereof; (ii) a one-time milestone payment of$7.0 million payable upon the first sale of the Purchased Product in any one of certain specified European countries; (iii) a one-time milestone payment of$3.0 million payable upon the first sale of the Purchased Product in Japan; and (iv) and quarterly earn-out payments equal to two percent (2%) of net sales ofthe Purchased Product during specified earn-out periods. Such earn-out payments are payable with respect to net sales in a country beginning on the date ofthe first sale in such country and ending on the earlier of (i) December 31, 2033 and (ii) fifteen years after the date of such sale, subject to early termination incertain circumstances if a biosimilar product is on the market in the applicable country. Because the achievement of these milestones is uncertain, theamounts have not been included in the ‘‘Contractual Obligations and Commitments’’ table above.License AgreementsLicense Agreement with the University of ZurichWe have a license agreement with Zurich, which grants us exclusive license rights, with the right to sublicense, to make, have made, use and sell undercertain patents primarily directed to our targeting agent, including EpCAM chimera and related immunoconjugates and methods of use and manufacture ofthe same. These patents cover some key aspects of our product candidate Vicinium.Under the terms of the agreement, we may be obligated to pay $0.8 million in milestone payments, for the first product candidate that achieves applicableclinical development milestones. Based on current clinical status, we anticipate that these milestones may be triggered by Vicinium’s clinical developmentpathway. As part of the consideration, we will also be obligated to pay up to a 4% royalty on the net product sales for products covered by or manufacturedusing a method covered by a valid claim in the Zurich patent rights. Royalties owed to Zurich will be reduced if the total royalty rate owed by us to Zurichand any other third party is 10% or greater, provided that the royalty rate may not be less than 2% of net sales. The obligation to pay royalties in a particularcountry expires upon the expiration or termination of the last of the Zurich patent rights that covers the manufacture, use or sale of a product. There is noobligation to pay royalties in a country if there is no valid claim that covers the product or a method of manufacturing the product.License Agreement with Merck KGaAWe have a license agreement with Merck, which grants us an exclusive license, with the right to sublicense, under certain patents and technology relating tothe de-immunization of our cytotoxin Bouganin for therapeutic and in vivo diagnostic purposes in humans. The de-immunized cytotoxin is known asdeBouganin and has been incorporated in to our product117Table of Contentscandidate, VB6-845d. We have the worldwide exclusive right, with the right to sublicense, under the licensed patents and technology to, among other things,make, have made, use or sell products incorporating deBouganin.Under the agreement, we may be obligated to make milestone payments in respect of certain stages of regulatory approval reached by a product candidategenerated by this technology or covered by a licensed patent, as well as royalties calculated with respect to net sales of these products.License Agreement with MicrometWe have a license agreement with Micromet AG, or Micromet, now part of Amgen, Inc., which grants us nonexclusive rights, with certain sublicense rights,for know-how and patents allowing exploitation of certain single chain antibody products. These patents cover some key aspects of Vicinium. Under theterms of the agreement, we may be obligated to pay up to €3.6 million in milestone payments, for the first product candidate that achieves applicable clinicaldevelopment milestones. Based on current clinical status, we anticipate that certain of these milestones may be triggered by Vicinium’s clinical developmentpathway. We are also required to pay up to a 3.5% royalty on the net sales for products covered by the agreement, which includes Vicinium. The royalty rateowed to Micromet in a particular country will be reduced to 1.5% if there are no valid claims covering the product in that country. The obligation to payroyalties in a particular country expires upon the later of the expiration date of the last valid claim covering the product and the tenth anniversary of the firstcommercial sale of the product in such country. Finally, we are required to pay to Micromet an annual license maintenance fee of €50,000, which can becredited towards any royalty payment we owe to Micromet.License Agreement with XOMAWe have a license agreement with XOMA Ireland Limited, or XOMA, which grants us non-exclusive rights to certain XOMA patent rights and know-howrelated to certain expression technology, including plasmids, expression strains, plasmid maps and production systems. These patents and related know-howcover some key aspects of Vicinium. Under the terms of the agreement, we are required to pay up to $250,000 in milestone payments for a product candidatethat incorporates know-how under the license and achieves applicable clinical development milestones. Based on current clinical status, we anticipate thatthese milestones may be triggered by Vicinium’s clinical development pathway. We are also required to pay a 2.5% royalty on the net sales for productsincorporating XOMA’s technology, which includes Vicinium. We have the right to reduce the amount of royalties owed to XOMA on a country-by-countrybasis by the amount of royalties paid to other third parties, provided that the royalty rate to XOMA may not be less than 1.75% of net sales. In addition, theforegoing royalty rates are reduced by 50% with respect to products that are not covered by a valid patent claim in the country of sale. The obligation to payroyalties in a particular country expires upon the later of the expiration date of the last valid claim covering the product and the tenth anniversary of the firstcommercial sale of the product in such country.Net Operating Loss CarryforwardsAs of December 31, 2018, we had $134.7 million of U.S. federal NOL carryforwards, state NOL carryforwards of $129.1 million and U.S. federal and stateresearch and development tax credit carryforwards of $2.0 million and $0.9 million, respectively, available to reduce future taxable income. Due to ourhistory of losses and lack of other positive evidence, we have determined that it is more likely than not that our deferred tax assets will not be realized, andtherefore, the deferred tax assets were fully reduced by a valuation allowance. $119.2 million of the U.S. federal NOL carryforwards and $129.1 million of thestate NOL carryforwards expire beginning 2030 through 2038. $15.5 million of the U.S. federal NOL carryforwards will be carried forward indefinitely. TheseU.S. federal and state tax credit carryforwards expire at various dates beginning in 2029 through 2038, if not utilized. Utilization of the NOLs and generalbusiness tax credits carryforwards may be subject to a substantial limitation under Sections 382 and 383 of the Internal Revenue Code of 1986 as amended,which we refer to as the Code, due to changes in ownership of our company that have occurred previously or that could occur in the future. These ownershipchanges may limit the amount of NOLs and general business tax credits carryforwards that can be utilized annually to reduce future taxable income and tax,respectively. In general, an ownership change, as defined by Section 382 of the Code, results from transactions increasing the ownership of “5-percentShareholders” (as defined in the Code) in the stock of a corporation by more than 50 percentage points over a three-year period. We have determined that it ismore likely than not that our net operating and tax credit amounts disclosed above are subject to a material limitation under Section 382. We may alsoexperience ownership changes in the future as a result of subsequent shifts in our stock ownership. As a result, if we generate taxable income, our ability touse our pre-change NOL and tax credits carryforwards to reduce U.S. federal and state taxable income may be subject to limitations, which could result inincreased future tax liability to us.118Table of ContentsOff-balance Sheet ArrangementsWe did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined in the rules and regulations of theSEC.Item 7A.Quantitative and Qualitative Disclosures About Market Risk.We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act and are not required to provide the information under this Item.Item 8.Financial Statements and Supplementary Data.Our financial statements, together with the report of our independent registered public accounting firm, appear on pages F-1 through F-35 of this AnnualReport on Form 10-K.Item 9.Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.There has been no change of accountants nor any disagreements with accountants on any matter of accounting principles or practices or financial disclosurerequired to be reported under this Item.Item 9A.Controls and Procedures.Evaluation of Disclosure Controls and ProceduresOur management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated the effectiveness of our disclosure controls andprocedures as of December 31, 2018. The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e)) under the Exchange Act,means controls and other procedures of a company that are designed to ensure that information required to be disclosed by a company in the reports that itfiles or submits under the Exchange Act is recorded, processed, summarized and reported, within the time period specified in the SEC’s rules and forms.Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by acompany in the reports that it files or submits under the Exchange Act is accumulated and communicated to the company’s management, including itsprincipal executive and principal financial officers, as appropriate to allow timely decisions regarding required disclosure. Our management recognizes thatany controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives andmanagement necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Based on the evaluation of ourdisclosure controls and procedures as of December 31, 2018, our Chief Executive Officer and Chief Financial Officer concluded that, as of such date, ourdisclosure controls and procedures were effective at the reasonable assurance level.Notwithstanding our assessment that, as noted below, our internal control over financial reporting was not effective as of December 31, 2018 related toaccounting for business combinations, our management concluded that our disclosure controls and procedures were effective at the reasonable assurancelevel. The material weakness in our internal control over financial reporting was attributable primarily to our lack of expertise in our finance and accountinggroup related to the accounting for business combinations.As more fully discussed below, to remediate the material weakness referenced above, we have implemented or have plans to implement the remediationinitiatives described below and will continue to evaluate the remediation and plan to implement additional measures in the future.Management’s Annual Report on Internal Control Over Financial ReportingOur management is responsible for establishing and maintaining adequate internal control over financial reporting as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act. Our internal control system was designed to provide reasonable assurance to our management and our board of directorsregarding the preparation and fair presentation of published financial statements. Because of its inherent limitations, internal control over financial reportingmay not prevent or detect misstatements. Projections of any evaluation of effectiveness to future periods are subject to the risk that controls may becomeinadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.119Table of ContentsOur management assessed the effectiveness of our internal control over financial reporting as of December 31, 2018. In making this assessment, ourmanagement used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission in Internal Control—IntegratedFramework (2013). Based on this evaluation, our management concluded that our internal control over financial reporting was not effective as ofDecember 31, 2018.Previously Identified Material WeaknessesAs of December 31, 2018 there was a material weakness, identified in 2016, in our controls over the financial reporting process related to businesscombinations. As a result of a lack of expertise in our finance and accounting group related to the accounting for business combinations, we lacked sufficientreview of assumptions used and conclusions reached from the perspective of a typical market participant used in the acquisition valuation model. While weimplemented processes and controls in 2017 and 2018 to remediate the material weakness over the review of assumptions related to business combinations,there have been no subsequent business combination transactions since the identification of the material weakness in 2016 that could be tested to provideevidence that the new controls operate effectively. As a result, our management concluded that our internal control over financial reporting was not effectiveas of December 31, 2018.Remediation StatusIn 2017 and 2018 , we implemented processes and changes to our internal control over financial reporting to remediate the material weakness identifiedabove. These actions included the engagement of independent consultants to aid our review of business combinations. However, there have been nosubsequent business combination transactions since the identification of the material weakness in 2016 that could be tested to provide evidence that the newcontrols operate effectively.Effective as of October 20, 2017, John McCabe resigned as our Chief Financial Officer and Richard Fitzgerald was appointed as our Interim Chief FinancialOfficer and on January 23, 2018, Mr. Fitzgerald was appointed as our Chief Financial Officer. In order to stabilize our remediation efforts in light of thistransition, we also retained consultants to assist with the review of assumptions used and conclusions reached from the perspective of a typical marketparticipant used in the acquisition valuation model for the final purchase price allocation. In connection with our remediation plan, we are continuing toevaluate steps to address the material weaknesses, which may include the addition of new personnel, including one or more employees to our financial andaccounting group and the engagement of independent consultants to aid in the review of our financial reporting process.Any actions we have taken or may take to remediate the above material weaknesses is subject to continued management review supported by testing, as wellas oversight by the audit committee of our board of directors. We cannot assure, in any way, even if we add one or more employees to our finance andaccounting group and/or engage an independent consultant, that material weaknesses or significant deficiencies will not occur in the future and that we willbe able to remediate such weaknesses or deficiencies in a timely manner, which could impair our ability to accurately and timely report our financialposition, results of operations or cash flows.This annual report does not include an attestation report of our registered independent public accounting firm regarding internal control over financialreporting. Our management’s report was not subject to attestation by our independent registered public accounting firm pursuant to rules of the SEC thatpermit emerging growth companies, which we are, to provide only management’s report in this annual report.Changes in Internal Control over Financial ReportingExcept as described above, there was no change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under theExchange Act) that occurred during the three months ended December 31, 2018 that has materially affected, or is reasonably likely to materially affect, ourinternal control over financial reporting.Item 9B.Other Information.None.120Table of ContentsPART III Item 10.Directors, Executive Officers and Corporate Governance.The information required by this Item will be set forth in our 2019 Proxy Statement to be filed with the SEC within 120 days of December 31, 2018, and isincorporated into this Annual Report on Form 10-K by reference.Our Board has adopted a written Code of Business Conduct and Ethics applicable to our directors, officers and employees, including our principal executiveofficer, principal financial officer, principal accounting officer or controller, or persons performing similar functions. The Code of Business Conduct andEthics covers fundamental ethical and compliance-related principles and practices such as accurate accounting records and financial reporting, avoidingconflicts of interest, the protection and use of our property and information and compliance with legal and regulatory requirements. A current copy of thecode is posted on the Corporate Governance section of our website, which is located at http://www.sesenbio.com. We intend to satisfy the disclosurerequirement under Item 5.05 of Form 8-K regarding any substantive amendment to, or waiver from, a provision of this Code and by posting such informationon the website address and location specified above.Item 11.Executive Compensation.The information required by this Item will be set forth in our 2019 Proxy Statement to be filed with the SEC within 120 days of December 31, 2018, and isincorporated into this Annual Report on Form 10-K by reference.Item 12.Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters.The information required by this Item will be set forth in our 2019 Proxy Statement to be filed with the SEC within 120 days of December 31, 2018, and isincorporated into this Annual Report on Form 10-K by reference.Item 13.Certain Relationships and Related Transactions, and Director Independence.The information required by this Item will be set forth in our 2019 Proxy Statement to be filed with the SEC within 120 days of December 31, 2018, and isincorporated into this Annual Report on Form 10-K by reference.Item 14.Principal Accountant Fees and Services.The information required by this Item will be set forth in our 2019 Proxy Statement to be filed with the SEC within 120 days of December 31, 2018, and isincorporated into this Annual Report on Form 10-K by reference.121Table of ContentsPART IVItem 15.Exhibits and Financial Statement Schedules.(a)(1) Financial StatementsThe following financial statements and supplementary data are included in Item 8 of this Annual Report on Form 10-K.Report of Independent Registered Public Accounting FirmF-2Consolidated Balance SheetsF-3Consolidated Statements of Operations and Comprehensive (Loss) IncomeF-4Consolidated Statements of Stockholders’ EquityF-5Consolidated Statements of Cash FlowsF-6Notes to Consolidated Financial StatementsF-7(a)(2) ExhibitsThe exhibits filed as part of this Annual Report on Form 10-K are set forth on the Exhibit Index immediately preceding such exhibits, and are incorporatedherein by reference.122Table of ContentsEXHIBIT INDEX ExhibitNo. Description 2.1 Share Purchase Agreement, effective as of September 20, 2016, by and between Eleven Biotherapeutics, Inc., Viventia Bio Inc. andClairmark Investments Ltd., as representative of the selling shareholders (we hereby agree to furnish supplementally a copy of any omittedschedules to the SEC upon request). Incorporated herein by reference to Exhibit 2.1 to our Current Report on Form 8-K filed on September21, 2016 (File No. 001-36296). 3.1 Restated Certificate of Incorporation of Eleven Biotherapeutics, Inc. Incorporated by reference to Exhibit 3.1 to our Current Report onForm 8-K filed on February 18, 2014 (File No. 001-36296). 3.2 Amended and Restated By-laws of Eleven Biotherapeutics, Inc. Incorporated by reference to Exhibit 3.1 to our Current Report on Form 8-Kfiled on April 16, 2015 (File No. 001-36296). 3.3 Certificate of Amendment of Certificate of Incorporation. Incorporated by reference to Exhibit 3.1 to our Current Report on Form 8-K filedon May 17, 2018 (File No. 001-36296). 3.4 Amendment to Amended and Restated By-laws. Incorporated by reference to Exhibit 3.2 to our Current Report on Form 8-K filed on May17, 2018 (File No. 001-36296). 4.1 Specimen Stock Certificate evidencing the shares of common stock. Incorporated by reference to Exhibit 4.1 to our Registration Statementon Form S-1/A filed on January 23, 2014 (Reg. No. 333-193131). 4.2 Amended and Restated Investors’ Rights Agreement of Eleven Biotherapeutics, Inc. Incorporated by reference to Exhibit 4.2 to ourRegistration Statement on Form S-1 filed on December 30, 2013 (Reg. No. 333-193131). 4.3 Registration Rights Agreement, dated as of September 20, 2016 by and among Eleven Biotherapeutics, Inc. and the shareholders namedtherein. Incorporated herein by reference to Exhibit 4.1 to our Current Report on Form 8-K filed on September 21, 2016 (File No. 001-36296). 4.4 Form of Warrant to Purchase Common Stock, by and between Eleven Biotherapeutics, Inc. and the persons party thereto. Incorporated byreference to Exhibit 10.2 to our Current Report on Form 8-K filed on December 1, 2014 (File No. 001-36296). 4.5 Form of Warrant issued to Silicon Valley Bank and Life Science Loans, LLC dated November 25, 2014. Incorporated by reference toExhibit 10.23 to our Registration Statement on Form S-1 filed with the SEC on December 19, 2014 (Reg. No. 333-201176). 4.6 Form of Common Warrant. Incorporated by reference to Exhibit 4.1 to our Current Report on Form 8-K filed with the SEC on November 3,2017 (File. No. 001-36296). 4.7 Form of Warrant. Incorporated by reference to Exhibit 4.1 to our Current Report on Form 8-K filed with the SEC on March 23, 2018 (File.No. 001-36296). 123Table of Contents10.1+ Amended and Restated 2009 Stock Incentive Plan. Incorporated by reference to Exhibit 10.1 to our Registration Statement on Form S-1filed on December 30, 2013 (Reg. No. 333-193131). 10.2+ Form of Incentive Stock Option Agreement under the Amended and Restated 2009 Stock Incentive Plan. Incorporated by reference toExhibit 10.2 to our Registration Statement on Form S-1 filed on December 30, 2013 (Reg. No. 333-193131). 10.3+ Form of Non-statutory Stock Option Agreement under the Amended and Restated 2009 Stock Incentive Plan. Incorporated by reference toExhibit 10.3 to our Registration Statement on Form S-1 filed on December 30, 2013 (Reg. No. 333-193131). 10.4+ Form of Restricted Stock Agreement under the Amended and Restated 2009 Stock Incentive Plan. Incorporated by reference to Exhibit10.4 to our Registration Statement on Form S-1 filed on December 30, 2013 (Reg. No. 333-193131). 10.5+ 2014 Stock Incentive Plan. Incorporated by reference to Exhibit 10.1 to our Registration Statement on Form S-8 POS filed on August 10,2018 (Reg. No. 333-224959). 10.6+ Form of Incentive Stock Option Agreement under 2014 Stock Incentive Plan. Incorporated by reference to Exhibit 10.6 to our RegistrationStatement on Form S-1/A filed on January 23, 2014 (Reg. No. 333-193131). 10.7+ Form of Non-statutory Stock Option Agreement under 2014 Stock Incentive Plan. Incorporated by reference to Exhibit 10.7 to ourRegistration Statement on Form S-1/A filed on January 23, 2014 (Reg. No. 333-193131). 10.8+ Form of Restricted Stock Unit Agreement under 2014 Stock Incentive Plan. Incorporated by reference to Exhibit 10.1 to our Current Reporton Form 8-K filed on June 29, 2015 (File No. 001-36296). 10.9 Form of Indemnification Agreement by and between Sesen Bio, Inc. and each of its directors and executive officers. Incorporated byreference to Exhibit 10.2 to our Registration Statement on our Current Report on Form 8-K filed with the SEC on December 4, 2018 (FileNo. 001-36296). 10.10+ 2014 Employee Stock Purchase Plan. Incorporated by reference to Exhibit 10.13 to our Registration Statement on Form S-1/A filed withthe SEC on January 23, 2014 (Reg. No. 333-193131). 10.11+ Employment Agreement, dated August 28, 2015, by and between Eleven Biotherapeutics, Inc. and John J. McCabe. Incorporated herein byreference to Exhibit 10.17 to our Annual Report on Form 10-K filed on March 24, 2016 (File No. 001-36296). 10.12+ Form of Director Restricted Stock Agreement under 2014 Stock Incentive Plan. Incorporated by reference to Exhibit 10.18 to ourRegistration Statement on Form S-1/A filed with the SEC on January 23, 2014 (Reg. No. 333-193131). 10.13† License Agreement, dated as of June 10, 2016, by and among Eleven Biotherapeutics, Inc., F. Hoffmann-La Roche Ltd and Hoffmann-LaRoche Inc. Incorporated herein by reference to Exhibit 10.1 to our Quarterly Report on Form 10-Q filed on August 12, 2016 (File No. 001-36296). 10.14† License Agreement, effective January 13, 2003, as amended and restated on October 14, 2015, by and between The University of Zurichand Viventia Bio Inc. Incorporated herein by reference to Exhibit 10.1 to our Current Report on Form 8-K filed on September 21, 2016(File No. 001-36296). 10.15† Amended & Restated Exclusive License Agreement, dated October 14, 2015, by and between Merck KGaA and Viventia Bio Inc.Incorporated herein by reference to Exhibit 10.2 to our Current Report on Form 8-K filed on September 21, 2016 (File No. 001-36296). 10.16 Amended and Restated License Agreement, dated October 17, 2014, by and between Clairmark Investments Ltd. (successor in interest ofProtoden Technologies Inc.) and Viventia Bio Inc. Incorporated herein by reference to Exhibit 10.3 to our Current Report on Form 8-Kfiled on September 21, 2016 (File No. 001-36296). 10.17+ Non-Exclusive Product License Agreement, effective as of October 18, 2005, by and between Micromet AG and Viventia Biotech Inc.Incorporated herein by reference to Exhibit 10.1 to our Quarterly Report on Form 10-Q filed on November 9, 2018 (File No. 001-36296). 10.18+ Non-Exclusive License Agreement, effective as of November 30, 2001, by and between XOMA Ireland Limited and Viventia Biotech Inc.Incorporated herein by reference to Exhibit 10.2 to our Quarterly Report on Form 10-Q filed on November 9, 2018 (File No. 001-36296). 124Table of Contents10.19+ Indenture, dated March 31, 2000, between 131-149 Hamelin Street Leaseholds Limited (successor in interest of Almad InvestmentsLimited) and Viventia Bio Inc. (successor in interest of Viventia Biotech Inc.), as amended by Lease Amending Agreement, dated June 26,2003, as further amended by Lease Amending Agreement, dated January 26, 2004, and as further amended by Letter Agreement, dated June25, 2008, and as further amended by Lease Amending Agreement, September 16, 2015. Incorporated herein by reference to Exhibit 10.4 toour Current Report on Form 8-K filed on September 21, 2016 (File No. 001-36296). 10.20+ Amendment to Retention Letter Agreement, dated March 5, 2017, by and between Eleven Biotherapeutics, Inc. and John J. McCabe.Incorporated herein by reference to Exhibit 10.1 to our Current Report on Form 8-K filed on March 6, 2017 (File No. 001-36296). 10.21+ Consulting Agreement, dated October 20, 2017, by and between Eleven Biotherapeutics, Inc. and John J. McCabe. Incorporated herein byreference to Exhibit 10.22 to our Annual Report on Form 10-K filed on April 2, 2018 (File No. 001-36296). 10.22+ Employment Agreement dated September 20, 2016 between Eleven Biotherapeutics, Inc. and Stephen A. Hurly. Incorporated herein byreference to Exhibit 10.8 to our Current Report on Form 8-K filed on September 21, 2016 (File No. 001-36296). 10.23+ Separation Agreement and General Release between Stephen Hurly and Sesen Bio, Inc. Incorporated by reference to Exhibit 10.1 to ourCurrent Report on Form 8-K filed on October 1, 2018 (File No. 001-36296). 10.24+ Employment Agreement, dated August 7, 2018, by and between Sesen Bio, Inc. and Thomas R. Cannell. Incorporated by reference toExhibit 10.1 to our Current Report on Form 8-K filed on August 13, 2018 (File No. 001-36296). 10.25 Agreement for Termination of Lease and Voluntary Surrender of Premises, dated October 14, 2016, between Eleven Biotherapeutics, Inc.and ARE-MA Region No. 38, LLC. Incorporated herein by reference to Exhibit 10.10 to our Quarterly Report on Form 10-Q filed onNovember 14, 2016 (File No. 001-36296). 10.26+ Amendment to Employment Agreement dated June 8, 2017 between Eleven Biotherapeutics, Inc. and Arthur P. DeCillis. Incorporatedherein by reference to Exhibit 10.1 to our Quarterly Report on Form 10-Q filed on August 14, 2017 (File No. 001-36296). 10.27+ Consulting Agreement, dated October 24, 2017, by and between Eleven Biotherapeutics, Inc. and DeCillis Consulting, LLC. Incorporatedherein by reference to Exhibit 10.27 to our Annual Report on Form 10-K filed on April 2, 2018 (File No. 001-36296). 10.28+ Consulting Agreement, effective as of October 13, 2017, by and between Eleven Biotherapeutics, Inc. and Richard F. Fitzgerald.Incorporated herein by reference to Exhibit 10.1 to our Current Report on Form 8-K filed on October 13, 2017 (File No. 001-36296). 10.29+ Employment Agreement, dated January 23, 2018, by and between Eleven Biotherapeutics, Inc. and Richard F. Fitzgerald. Incorporatedherein by reference to Exhibit 10.1 to our Current Report on Form 8-K filed on January 25, 2018 (File No. 001-36296). 10.30 Form of Securities Purchase Agreement. Incorporated by reference to Exhibit 10.1 to our Current Report on Form 8-K filed with the SEC onMarch 23, 2018 (File. No. 001-36296). 10.31 Employment Agreement, dated December 3, 2018, by and between Sesen Bio, Inc. and Dennis Kim, M.D., MPH. Incorporated by referenceto Exhibit 10.1 to our Current Report on Form 8-K filed on December 4, 2018 (File. No. 001-36296). 10.32* Stock Option Award Agreement, dated August 7, 2018, by and between Sesen Bio, Inc. and Thomas R. Cannell, D.V.M. 10.33* Stock Option Award Agreement, dated December 3, 2018, by and between Sesen Bio, Inc. and Dennis Kim, M.D. 10.34* Master Bioprocessing Services Agreement, dated October 4, 2018, between Sesen Bio, Inc. and FUJIFILM Diosynth BiotechnologiesU.S.A., Inc. 21.1* Subsidiaries of Sesen Bio, Inc. 23.1* Consent of Ernst & Young LLP 31.1* Rule 13a-14(a) Certification of Principal Executive Officer 31.2* Rule 13a-14(a) Certification of Principal Financial Officer 32.1* Certification of Principal Executive Officer and Principal Financial Officer pursuant to 18 U.S.C. §1350 125Table of Contents101.INS* XBRL Instance Document 101.SCH* XBRL Taxonomy Extension Schema Document 101.CAL* XBRL Taxonomy Extension Calculation Linkbase Document 101.DEF* XBRL Taxonomy Extension Definition Linkbase Document 101.LAB* XBRL Taxonomy Extension Label Linkbase Document 101.PRE* XBRL Taxonomy Extension Presentation Linkbase Document*Filed herewith.+This exhibit is a compensatory plan or arrangement in which our executive officers or directors participate.†Confidential treatment requested as to portions of the exhibit. Confidential materials omitted and filed separately with the Securities and ExchangeCommission.(a)(3) Financial Statement SchedulesSchedules are omitted because they are not applicable, or are not required, or because the information is included in the Consolidated Financial Statementsand Notes thereto.Item 16.Form 10-K Summary.Not applicable.126Table of ContentsSIGNATURESPursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on itsbehalf by the undersigned, thereunto duly authorized.SESEN BIO, INC. By: /s/ Thomas R. Cannell, D.V.M. Thomas R. Cannell, D.V.M. President and Chief Executive OfficerMarch 1, 2019Pursuant to the requirements of the Securities and Exchange Act of 1934, this report has been signed below by the following persons on behalf of theregistrant and in the capacities and on the dates indicated. /s/ Thomas R. Cannell, D.V.M. Director, President and Chief Executive Officer (PrincipalExecutive Officer)March 1, 2019Thomas R. Cannell, D.V.M. /s/ Richard F. Fitzgerald Chief Financial Officer (Principal Financial and AccountingOfficer)March 1, 2019Richard F. Fitzgerald /s/ Wendy L. Dixon, Ph.D. Chair of the Board of DirectorsMarch 1, 2019Wendy L. Dixon, Ph.D. /s/ Leslie Dan, B.Sc. Phm,. M.B.A., C.M. DirectorMarch 1, 2019Leslie Dan, B.Sc. Phm,. M.B.A., C.M. /s/ Jay S. Duker, M.D. DirectorMarch 1, 2019Jay S. Duker, M.D. /s/ Jane V. Henderson DirectorMarch 1, 2019Jane V. Henderson /s/ Daniel S. Lynch DirectorMarch 1, 2019Daniel S. Lynch 127Table of ContentsINDEX TO FINANCIAL STATEMENTS Report of Independent Registered Public Accounting FirmF-2Consolidated Balance SheetsF-3Consolidated Statements of Operations and Comprehensive (Loss) IncomeF-4Consolidated Statements of Stockholders’ EquityF-5Consolidated Statements of Cash FlowsF-6Notes to Consolidated Financial StatementsF-7F-1Table of ContentsREPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRMTo the Stockholders and Board of Directors of Sesen Bio, Inc.Opinion on the Financial StatementsWe have audited the accompanying consolidated balance sheets of Sesen Bio, Inc. (the “Company”) as of December 31, 2018 and 2017, the relatedconsolidated statements of operations and comprehensive (loss) income, stockholders’ equity and cash flows for each of the three years in the period endedDecember 31, 2018, and the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financialstatements present fairly, in all material respects, the financial position of the Company at December 31, 2018 and 2017, and the results of its operations andits cash flows for each of the three years in the period ended December 31, 2018, in conformity with U.S. generally accepted accounting principles.The Company’s Ability to Continue as a Going ConcernThe accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note1 to the financial statements, the Company has suffered recurring losses from operations, has insufficient cash resources, and has stated that substantial doubtexists about the Company’s ability to continue as a going concern. Management’s evaluation of the events and conditions and management’s plansregarding these matters are also described in Note 1. The consolidated financial statements do not include any adjustments that might result from theoutcome of this uncertainty.Basis for OpinionThese financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financialstatements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB)and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations ofthe Securities and Exchange Commission and the PCAOB.We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonableassurance about whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, norwere we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding ofinternal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control overfinancial reporting. Accordingly, we express no such opinion.Our audits included performing procedures to assess the risks of material misstatement of the financial statements whether due to error or fraud, andperforming procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures inthe financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well asevaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion./s/ Ernst & Young LLPWe have served as the Company’s auditor since 2010.Boston, MassachusettsMarch 1, 2019F-2Table of ContentsSESEN BIO, INC.CONSOLIDATED BALANCE SHEETS(in thousands, except share and per share data) December 31, 2018 2017Assets Current assets: Cash and cash equivalents$50,422 $14,680Prepaid expenses and other current assets1,334 301Total current assets51,756 14,981Property and equipment, net321 522Restricted cash20 10Intangible assets46,400 46,400Goodwill13,064 13,064Other assets— 120Total assets$111,561 $75,097Liabilities and stockholders’ equity Current liabilities: Accounts payable$1,367 $907Accrued expenses4,746 3,813Total current liabilities6,113 4,720Other liabilities313 215Deferred tax liability12,528 12,528Contingent consideration48,400 39,600Commitments and contingencies (Note 9) Stockholders’ equity: Preferred stock, $0.001 par value per share; 5,000,000 shares authorized at December 31, 2018 and 2017and no shares issued and outstanding at December 31, 2018 and 2017— —Common stock, $0.001 par value per share; 200,000,000 shares authorized at December 31, 2018 and2017 and 77,456,180 and 34,702,565 shares issued and outstanding at December 31, 2018 and 2017,respectively77 35Additional paid-in capital230,154 170,330Accumulated deficit(186,024) (152,331)Total stockholders’ equity44,207 18,034Total liabilities and stockholders’ equity$111,561 $75,097See accompanying notes.F-3Table of ContentsSESEN BIO, INC.CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE (LOSS) INCOME(in thousands, except per share data) Year Ended December 31, 2018 2017 2016Revenue: Collaboration revenue$— $— $406 License revenue— 425 29,575Total revenue— 425 29,981Operating expenses: Research and development14,077 12,510 13,479General and administrative11,623 8,070 14,736Loss (gain) from change in fair value of contingent consideration8,800 9,100 (1,100)Total operating expenses34,500 29,680 27,115(Loss) income from operations(34,500) (29,255) 2,866Other income (expense): Other income (expense), net807 226 (723)Interest expense— — (247)Total other income (expense), net807 226 (970)Net (loss) income before income taxes(33,693) (29,029) 1,896 Provision for income taxes— — 5Net (loss) income and comprehensive (loss) income$(33,693) $(29,029) $1,891Net (loss) income per share applicable to common stockholders—basic$(0.55) $(1.11) $0.09Weighted-average number of common shares used in net (loss) income per shareapplicable to common stockholders—basic61,774 26,105 21,083Net (loss) income per share applicable to common stockholders-diluted$(0.55) $(1.11) $0.09Weighted-average number of common shares used in net (loss) income per shareapplicable to common stockholders—diluted61,774 26,105 21,733See accompanying notes.F-4Table of ContentsSESEN BIO, INC.CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY(in thousands, except share data) Common Stock AdditionalPaid-inCapital AccumulatedDeficit Stockholders’Equity Shares Amount (in thousands, except share data)Balance at December 31, 201519,619,124 20 144,126 (125,202) 18,944Exercise of stock options and vesting of restricted stockawards810,538 1 268 — 269Issuance of common stock pursuant to the ESPP88,871 — 35 — 35Issuance of common stock in connection with theacquisition of Viventia4,013,431 4 13,521 — 13,525Stock-based compensation expense— — 4,013 — 4,013Net income— — — 1,891 1,891Balance at December 31, 201624,531,964 25 161,963 (123,311) 38,677Cumulative effect of adoption of ASU 2016-09 (9) 9 —Exercise of stock options and vesting of restricted stockawards161,453 — 40 — 40Issuance of common stock pursuant to the ESPP9,148 — 12 — 12Issuance of common stock and common stock warrants, netof issuance costs of $1 million5,525,000 6 6,902 — 6,908Exercise of pre-funded common stock warrants4,475,000441—45Stock-based compensation expense— — 1,381 1,381Net loss— — — (29,029) (29,029)Balance at December 31, 201734,702,565 35 170,330 (152,331) 18,034Exercise of stock options and vesting of restricted stockawards443,443 — 277 — 277Issuance of common stock pursuant to the ESPP20,992 — 20 — 20Exercise of common stock warrants8,765,496 9 7,306 — 7,315Issuance of common stock and common stock warrants, netof issuance costs of $5.1 million33,523,684 33 50,938 — 50,971Stock-based compensation expense— — 1,283 1,283Net loss— — — (33,693) (33,693)Balance at December 31, 201877,456,180 $77 $230,154 $(186,024) $44,207See accompanying notes.F-5Table of ContentsSESEN BIO, INC.CONSOLIDATED STATEMENTS OF CASH FLOWS(in thousands) Year Ended December 31, 2018 2017 2016Operating activities Net (loss) income$(33,693) $(29,029) $1,891Adjustments to reconcile net (loss) income to net cash (used in) provided by operating activities: Depreciation208 285 178Non-cash interest expense— — 26Stock-based compensation expense1,283 1,381 4,013Change in fair value of warrant liability— (5) (110)Loss (gain) from change in fair value of contingent consideration8,800 9,100 (1,100)Loss on extinguishment of debt— — 221Gain on sale of equipment(5) (108) (24)Changes in operating assets and liabilities: Prepaid expenses and other assets(913) 164 800Accounts payable460 (760) (742)Accrued expenses and other liabilities1,031 1,746 (1,936)Deferred revenue— (425) 19Due to related party— (114) (698)Net cash (used in) provided by operating activities(22,829) (17,765) 2,538Investing activities Cash acquired in acquisition— — 136Sales (purchases) of property and equipment(2) 98 325Net cash provided by (used in) investing activities(2) 98 461Financing activities Payments on equipment financing and notes payable— — (14,124)Proceeds from issuance of common stock and common stock warrants, net of issuance costs58,286 6,908 —Proceeds from exercise of common stock options and common stock warrants277 85 269Proceeds from sale of common stock pursuant to ESPP20 12 35Net cash provided by (used in) financing activities58,583 7,005 (13,820)Net decrease in cash, cash equivalents and restricted cash35,752 (10,662) (10,821)Cash, cash equivalents and restricted cash at beginning of period14,690 25,352 36,173Cash, cash equivalents and restricted cash at end of period$50,442 $14,690 $25,352Supplemental non-cash investing and financing activities Common stock issued in connection with the acquisition (Note 3)— — 13,525Fair value of assets acquired and liabilities assumed in the acquisition (Note 3): Fair value of assets acquired in the acquisition, excluding cash$— $— $79,366Fair value of liabilities assumed in the acquisition$— $— $19,777Adjustment to fair value of assets acquired and liabilities assumed during provisional period (Note 3)$— $14,600 $—Issuance of warrants to purchase common stock$— $2,679 $—Supplemental cash flow information Cash paid for interest$— $— $663See accompanying notes.F-6Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS1. Organization and Basis of PresentationSesen Bio, Inc. (the “Company”), a Delaware corporation formed on February 25, 2008, is a biologics oncology company primarily focused on designing,engineering and developing targeted fusion protein therapeutics ("TFPTs"). The Company's TFPTs are single protein therapeutics composed of targetingdomains genetically fused via peptide linkers to cytotoxic protein payloads that are produced through the Company's proprietary one-step manufacturingprocess. The Company targets tumor cell surface antigens that allow for rapid internalization into the targeted cancer cell and have limited expression onnormal cells. The Company has designed its TFPTs to overcome the fundamental efficacy and safety challenges inherent in existing antibody drugconjugates ("ADCs"), where a payload is chemically attached to a targeting antibody.LiquidityThe Company has financed its operations to date primarily through private placements of its common stock and preferred stock, and convertible bridge notes,venture debt borrowings, its initial public offering ("IPO"), secondary offerings, sales effected in an "at-the-market" offering, and the License Agreement withRoche. As of December 31, 2018, the Company had cash and cash equivalents totaling approximately $50.4 million, net working capital of $45.6 millionand an accumulated deficit of $186.0 million.Under ASC 205-40, Going Concern, management must evaluate whether there are conditions or events, considered in the aggregate, that raise substantialdoubt about the Company’s ability to continue as a going concern within one year after the date that the financial statements are issued. This evaluationinitially does not take into consideration the potential mitigating effect of management’s plans that have not been fully implemented as of the date thefinancial statements are issued. When substantial doubt exists, management evaluates whether the mitigating effect of its plans sufficiently alleviatessubstantial doubt about the Company’s ability to continue as a going concern. The mitigating effect of management’s plans, however, is only considered ifboth (1) it is probable that the plans will be effectively implemented within one year after the date that the financial statements are issued, and (2) it isprobable that the plans, when implemented, will mitigate the relevant conditions or events that raise substantial doubt about the entity’s ability to continueas a going concern within one year after the date that the financial statements are issued. Generally, to be considered probable of being effectivelyimplemented, the plans must have been approved by the Company’s board of directors ("Board") before the date that the financial statements are issued. The future success of the Company is dependent on its ability to develop its product candidates and ultimately upon its ability to attain profitableoperations. The Company is subject to a number of risks similar to other early-stage life science companies, including, but not limited to, successfuldiscovery and development of its product candidates, raising additional capital with favorable terms, development by its competitors of new technologicalinnovations, protection of proprietary technology and market acceptance of the Company’s products. The successful discovery and development of productcandidates requires substantial working capital which may not be available to the Company on favorable terms or not at all.To date, the Company has no revenue from product sales and management expects continuing operating losses in the future. As of December 31, 2018, theCompany had available cash and cash equivalents of $50.4 million, which it does not believe is sufficient to fund the Company's current operating plan for atleast twelve months after the date the consolidated financial statements are issued. Management expects to seek additional funds through equity or debtfinancings or through additional collaboration, licensing transactions or other sources. The Company may be unable to obtain equity or debt financings orenter into additional collaboration or licensing transactions and, if necessary, the Company will be required to implement cost reduction strategies. Thesefactors raise substantial doubt about the Company’s ability to continue as a going concern. The accompanying consolidated financial statements have beenprepared on a going concern basis, which contemplates the realization of assets and satisfaction of liabilities in the ordinary course of business. Theconsolidated financial statements do not include any adjustments relating to the recoverability and classification of recorded asset amounts or the amountsand classification of liabilities that might result from the outcome of this uncertainty.2. Significant Accounting PoliciesF-7Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)Principles of ConsolidationThese consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”). The consolidatedfinancial statements include the accounts of Sesen Bio, Inc., its wholly owned subsidiary, Viventia Bio Inc., and its indirect subsidiaries, Viventia BioUSA Inc. and Viventia Biotech (EU) Limited. All inter-company transactions and balances have been eliminated in consolidation.Use of EstimatesThe preparation of consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect theamounts reported in the consolidated financial statements and accompanying notes. Management considers many factors in selecting appropriate financialaccounting policies and controls, and in developing the estimates and assumptions that are used in the preparation of these consolidated financial statements.Management must apply significant judgment in this process. In addition, other factors may affect estimates, including: expected business and operationalchanges, sensitivity and volatility associated with the assumptions used in developing estimates, and whether historical trends are expected to berepresentative of future trends. The estimation process often may yield a range of potentially reasonable estimates of the ultimate future outcomes andmanagement must select an amount that falls within that range of reasonable estimates. This process may result in actual results differing materially fromthose estimated amounts used in the preparation of the consolidated financial statements. Estimates are used in the following areas, among others: stock-based compensation expense, fair value of warrants to purchase common stock, revenue recognition, fair value of intangible assets and goodwill, incometaxes including the valuation allowance for deferred tax assets, accrued expenses, contingent consideration and going concern considerations. Actual resultscould differ from those estimates under different assumptions or conditions. Changes in estimates are reflected in reported results in the period in which theybecome known.Revenue RecognitionThe Company recognizes revenue in accordance with ASC 606, which supersedes all existing revenue recognition requirements, including most industry-specific guidance. The new standard requires a company to recognize revenue when it transfers goods or services to customers in an amount that reflects theconsideration that the company expects to receive for those goods or services. The new standard was effective on January 1, 2018 and the Company adoptedthis standard using the modified retrospective approach. As a result of this adoption, no amounts were recorded as a cumulative effect adjustment toaccumulated deficit as of January 1, 2018. We enter into collaboration agreements with strategic partners for the development and commercialization ofproduct candidates which are within the scope of ASC 606. Under these agreements, we license rights to certain of the our product candidates and maycomplete other performance obligations, such as the delivery of drug product or research and development services. The terms of these arrangementstypically include payment of non-refundable upfront fees, milestone payments, and royalties on net sales of licensed products and may also containadditional payment provisions.Under ASC 606, an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the considerationwhich the entity expects to receive in exchange for those goods or services. To determine the appropriate amount of revenue to be recognized forarrangements determined to be within the scope of ASC 606, we perform the following five steps: (i) identification of the promised goods or services in thecontract, (ii) determination of whether the promised goods or services are performance obligations including whether they are distinct in the context of thecontact, (iii) measurement of the transaction price, including the constraint on variable consideration, (iv) allocation of the transaction price to theperformance obligations, and (v) recognition of revenue when we satisfy each performance obligation. We only applie the five-step model to contracts whenit is probable that the entity will collect consideration it is entitled to in exchange for the goods or services it transfers to the customer.We estimate the transaction price based on the amount expected to be received for transferring the promised goods or services in the contract. Theconsideration may include fixed consideration or variable consideration. At the inception of each arrangement that includes variable consideration, weevaluate the amount of potential payments and the likelihood that the payments will be received. We utilize either the most likely amount method orexpected amount method to estimate the amount expected to be received based on which method best predicts the amount expected to be received. Theamount of variable consideration which is included in the transaction price may be constrained, and is included in the transaction price only to the extentthat it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period.F-8Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)Our contracts include development and regulatory milestone payments which are assessed under the most likely amount method and constrained if it isprobable that a significant revenue reversal would occur. At the end of each reporting period, we re-evaluate the probability of achievement of suchmilestones and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on acumulative catch-up basis, which would affect revenue in the period of adjustment.For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and the license is deemed to be thepredominant item to which the royalties relate, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation towhich some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, we have not recognized any consideration related tosales-based royalty revenue resulting from any of the our collaboration arrangements.We allocates the transaction price based on the estimated stand-alone selling price of each of the performance obligations. We must develop assumptions thatrequire judgment to determine the stand-alone selling price for each performance obligation identified in the contract.The consideration allocated to each performance obligation is recognized as revenue when control is transferred for the related goods or services.Research and Development CostsExpenditures relating to research and development are expensed in the period incurred. Research and development expenses consist of both internal andexternal costs associated with all basic research activities, clinical activities and technical effort required to develop a new product or service. The researchand development costs include personnel-related costs, stock-based compensation, facilities, research-related overhead, pre-approval regulatory and clinicaltrial costs, manufacturing costs and other contracted services, license fees, and other external costs.In certain circumstances, the Company is required to make advance payments to vendors for goods or services that will be received in the future for use inresearch and development activities. In such circumstances, the advance payments are deferred and are expensed when the activity has been performed orwhen the goods have been received.Stock-Based CompensationThe Company accounts for its stock-based compensation awards in accordance with ASC Topic 718, Compensation—Stock Compensation (“ASC 718”).ASC 718 requires all stock-based payments to employees and directors, including grants of employee stock options, to be recognized as expense in theconsolidated financial statements based on their grant date fair values. For stock options granted to employees and to members of the Board for their serviceson the Board, the Company estimates the grant date fair value of each option award using the Black-Scholes option-pricing model. The use of the Black-Scholes option-pricing model requires management to make assumptions with respect to the expected term of the option, the expected volatility of thecommon stock consistent with the expected life of the option, risk-free interest rates and expected dividend yields of the common stock. For awards subject toservice-based vesting conditions, the Company recognizes stock-based compensation expense equal to the grant date fair value of the stock options on astraight-line basis over the requisite service period. Forfeitures are recognized as they occur. For awards subject to performance-based vesting conditions, theCompany recognizes stock-based compensation expense using an accelerated recognition method.The Company expenses restricted stock awards and restricted stock units to employees and members of the Board based on the grant date fair value of theaward on a straight-line basis over the associated service period of the award. Awards of restricted stock to non-employees are adjusted through stock-basedcompensation expense at each reporting period end to reflect the current fair value of such awards and expensed on a straight-line basis.The Company records the expense for stock option grants subject to performance-based milestone vesting using the accelerated attribution method over theremaining service period when management determines that achievement of the milestone is probable. Management evaluates when the achievement of aperformance-based milestone is probable based on the relative satisfaction of the performance conditions as of the reporting date.F-9Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)Share-based payments issued to non-employees are recorded at their fair values, and are periodically revalued as the equity instruments vest and arerecognized as expense over the related service period in accordance with the provisions of ASC 718 and ASC Topic 505-50, Equity-Based Payments to Non-Employees. For equity instruments granted to non-employees, the Company recognizes stock-based compensation expense on a straight-line basis. Share-based expense related to non-employees during the years presented is immaterial.During the years ended December 31, 2018, 2017 and 2016, the Company recorded stock-based compensation expense, which was allocated as follows in theconsolidated statements of operations and comprehensive (loss) income (in thousands): Year Ended December 31, 2018 2017 2016Research and development expense$505 $404 $1,455General and administrative expense778 977 2,558 $1,283 $1,381 $4,013No related tax benefits were recognized for the years ended December 31, 2018, 2017 and 2016.Income TaxesThe Company provides for income taxes using the liability method. Under this method, deferred tax assets and liabilities are determined based on differencesbetween the financial statement carrying amounts and the tax bases of the assets and liabilities using the enacted tax rates in effect in the years in which thedifferences are expected to reverse. A valuation allowance against deferred tax assets is recorded if, based on the weight of the available evidence, it is morelikely than not that some or all of the deferred tax assets will not be realized.The Company accounts for uncertain tax positions in accordance with the provisions of ASC 740, Income Taxes. When uncertain tax positions exist, theCompany recognizes the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether thetax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts andcircumstances. As of December 31, 2018 and 2017, the Company did not have any significant uncertain tax positions.Comprehensive (Loss) IncomeComprehensive (loss) income is defined as the change in equity of a business enterprise during a period from transactions and other events and circumstancesfrom non-owner sources. For the years ended December 31, 2018, 2017 and 2016, comprehensive (loss) income was equal to net (loss) income.Cash and Cash EquivalentsThe Company considers highly liquid investments with a maturity of three months or less when purchased to be cash equivalents.Concentrations of Credit Risk and Off-Balance-Sheet RiskThe Company has no significant off-balance-sheet risk, such as foreign exchange contracts, option contracts, or other foreign hedging arrangements.Financial instruments that potentially expose the Company to concentrations of credit risk primarily consist of cash and cash equivalents. The Companyplaces its cash and cash equivalents in a custodian account in accredited financial institutions.Fair Value of Financial InstrumentsThe fair value hierarchy prioritizes the inputs to valuation techniques used to measure fair value into three broad levels as follows: Level 1 inputs are quotedprices (unadjusted) in active markets for identical assets or liabilities; Level 2 inputs are inputs other than quoted prices included within Level 1 that areobservable for the asset or liability, either directly or indirectly; and Level 3 inputs are unobservable inputs that reflect the Company’s own assumptionsabout what the assumptions marketF-10Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)participants would use in pricing the asset or liability. Financial assets and liabilities are classified in their entirety based on the lowest level of input that issignificant to the fair value measurement.The following table presents information about the Company’s financial assets and liabilities that have been measured at fair value, and indicates the fairvalue hierarchy of the valuation inputs utilized to determine such fair value. The Company determines the fair value of the contingent consideration (SeeNote 3) using Level 3 inputs.The following table summarizes the assets and liabilities measured at fair value on a recurring basis at December 31, 2018 (in thousands):DescriptionDecember 31, 2018 ActiveMarkets(Level 1) ObservableInputs(Level 2) UnobservableInputs(Level 3)Assets: Cash and cash equivalents$50,422 $50,422 $— $—Restricted cash20 20 — —Total assets$50,442 $50,442 $— $—Liabilities: Contingent consideration48,400 — — 48,400Total liabilities$48,400 $— $— $48,400The following table summarizes the assets and liabilities measured at fair value on a recurring basis at December 31, 2017 (in thousands): DescriptionDecember 31, 2017 ActiveMarkets(Level 1) ObservableInputs(Level 2) UnobservableInputs(Level 3)Assets: Cash and cash equivalents$14,680 $14,680 $— $—Restricted cash10 10 — —Total assets$14,690 $14,690 $— $—Liabilities: Contingent consideration39,600 — — 39,600Total liabilities$39,600 $— $— $39,600The carrying amounts reflected in the balance sheets for prepaid expenses and other current assets, other assets, accounts payable and accrued expensesapproximate their fair values at December 31, 2018 and 2017, due to their short-term nature.There have been no changes to the valuation methods used during the years ended December 31, 2018 and 2017. The Company evaluates transfers betweenlevels at the end of each reporting period. There were no transfers of assets or liabilities between levels during the years ended December 31, 2018 and 2017.Property and EquipmentProperty and equipment consists of lab equipment, furniture and fixtures, computer equipment, software, and leasehold improvements. Expenditures formaintenance and repairs are recorded to expense as incurred. Major betterments are capitalized as additions to property and equipment. Depreciation iscalculated over the estimated useful lives of the assets using the straight-line method.Business CombinationsThe Company evaluates acquisitions of assets and other similar transactions to assess whether or not the transaction should be accounted for as a businesscombination by assessing whether or not the Company has acquired inputs and processes that have the ability to create outputs. If determined to be abusiness combination, the Company accounts for business acquisitions underF-11Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)the acquisition method of accounting as indicated in the FASB issued ASC Topic 805, Business Combinations (“ASC 805”), which requires the acquiringentity in a business combination to recognize the fair value of all assets acquired and liabilities assumed and establishes the acquisition date as the fair valuemeasurement point. Accordingly, the Company recognizes assets acquired and liabilities assumed in business combinations, including contingent assets andliabilities, and non-controlling interest in the acquiree based on the fair value estimates as of the date of acquisition. In accordance with ASC 805, theCompany recognizes and measures goodwill as of the acquisition date, as the excess of the fair value of the consideration paid over the fair value of theidentified net assets acquired.The consideration for the Company’s business acquisitions includes future payments that are contingent upon the occurrence of a particular event or events.The obligations for such contingent consideration payments are recorded at fair value on the acquisition date. The contingent consideration obligations arethen evaluated each reporting period. Changes in the fair value of contingent consideration obligations, other than changes due to payments, are recognizedas a gain or loss on fair value remeasurement of contingent consideration in the consolidated statements of operations and comprehensive (loss) income.Indefinite-Lived Intangible AssetsIn accordance with ASC Topic 350, Intangibles — Goodwill and Other (“ASC 350”), during the period that an asset is considered indefinite-lived, such as in-process research and development (“IPR&D”), it will not be amortized. Acquired IPR&D represents the fair value assigned to research and development assetsthat have not reached technological feasibility. The value assigned to acquired IPR&D is determined by estimating the costs to develop the acquiredtechnology into commercially viable products, estimating the resulting revenue from the projects, and discounting the net cash flows to present value. Therevenue and costs projections used to value acquired IPR&D are, as applicable, reduced based on the probability of success of developing a new drug.Additionally, the projections consider the relevant market sizes and growth factors, expected trends in technology, and the nature and expected timing ofnew product introductions by the Company and its competitors. The rates utilized to discount the net cash flows to their present value are commensurate withthe stage of development of the projects and uncertainties in the economic estimates used in the projections. Upon the acquisition of IPR&D, the Companycompletes an assessment of whether its acquisition constitutes the purchase of a single asset or a group of assets. Multiple factors are considered in thisassessment, including the nature of the technology acquired, the presence or absence of separate cash flows, the development process and stage ofcompletion, quantitative significance and the rationale for entering into the transaction. Indefinite-lived assets are maintained on the Company’sconsolidated balance sheet until either the project underlying it is completed or the asset becomes impaired. Indefinite-lived assets are tested for impairmenton an annual basis, or whenever events or changes in circumstances indicate the reduction in the fair value of the IPR&D asset is below its respective carryingamount. If the Company determines that an impairment has occurred, a write-down of the carrying value and an impairment charge to operating expenses inthe period the determination is made is recorded. When development of an IPR&D asset is complete, the associated asset would be deemed finite-lived andwould then be amortized over its respective estimated useful life at that point.GoodwillGoodwill represents the difference between the purchase price and the fair value of the identifiable tangible and intangible net assets when accounted forusing the purchase method of accounting. Goodwill is not amortized, but is reviewed for impairment. The Company tests its goodwill for impairmentannually, or whenever events or changes in circumstances indicate an impairment may have occurred, by comparing its carrying value to its implied fairvalue in accordance with ASC 350. Impairment may result from, among other things, deterioration in the performance of the acquired asset, adverse marketconditions, adverse changes in applicable laws or regulations and a variety of other circumstances. If the Company determines that an impairment hasoccurred, a write-down of the carrying value and an impairment charge to operating expenses in the period the determination is made is recorded. Inevaluating the carrying value of goodwill, the Company must make assumptions regarding estimated future cash flows and other factors to determine the fairvalue of the reporting unit. Changes in strategy or market conditions could significantly impact those judgments in the future and require an adjustment tothe recorded balances.Impairment of Long-Lived AssetsThe Company periodically evaluates its long-lived assets for potential impairment in accordance with ASC Topic 360, Property, Plant and Equipment.Potential impairment is assessed when there is evidence that events or changes in circumstances indicate that the carrying amount of an asset may not berecovered. Recoverability of these assets is assessed based on undiscountedF-12Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)expected future cash flows from the assets, considering a number of factors, including past operating results, budgets and economic projections, market trendsand product development cycles. If impairments are identified, assets are written down to their estimated fair value. The Company recognized a de minimisamount of impairment charges in the year ended December 31, 2017 related to the strategic restructuring of the Company in August 2017. The Company didnot recognize any impairment charges for the years ended December 31, 2018 and 2016, respectively.Warrant LiabilityThe Company accounts for warrant instruments that either conditionally or unconditionally obligate the issuer to transfer assets as liabilities regardless of thetiming of the redemption feature or price, even though the underlying shares may be classified as permanent or temporary equity. Certain warrants, issued inDecember 2014, were subject to revaluation at each balance sheet date, and any changes in fair value were recorded as a component of other income(expense), until the earlier of their exercise or expiration or upon the completion of a liquidation event. These warrants expired un-exercised in December2017.Contingent ConsiderationIn connection with the acquisition of Viventia Bio Inc., the Company recorded contingent consideration pertaining to the amounts potentially payable toViventia Bio Inc.'s Selling Shareholders pursuant to the Share Purchase Agreement (See Note 3). Contingent consideration is measured at fair value and isbased on significant inputs not observable in the market, which represents a Level 3 measurement within the fair value hierarchy. The valuation of contingentconsideration uses assumptions the Company believes would be made by a market participant. The Company assesses these estimates on an on-going basis asadditional data impacting the assumptions is obtained. Future changes in the fair value of contingent consideration related to updated assumptions andestimates are recognized within the consolidated statements of operations and comprehensive (loss) income.Contingent consideration may change significantly as development progresses and additional data are obtained, impacting the Company’s assumptionsregarding probabilities of successful achievement of related milestones used to estimate the fair value of the liability and the timing in which they areexpected to be achieved. In evaluating the fair value information, considerable judgment is required to interpret the market data used to develop theestimates. The estimates of fair value may not be indicative of the amounts that could be realized in a current market exchange. Accordingly, the use ofdifferent market assumptions and/or different valuation techniques could result in materially different fair value estimates. The following table sets forth asummary of changes in the fair value of the Company's contingent consideration liability, which represented a recurring measurement classified within Level3 of the fair value hierarchy, wherein fair value was estimated using significant unobservable inputs (in thousands):Beginning balance, January 1, 2018$39,600Loss from change in fair value of contingent consideration8,800Ending balance, December 31, 2018$48,400The fair value of the Company’s contingent consideration was determined using probabilities of successful achievement of regulatory milestones andcommercial sales, the period in which these milestones and sales are expected to be achieved ranging from 2020 to 2033, the level of commercial sales ofVicinium, and discount rates ranging from 8.3% to 10.5% as of December 31, 2017 and 6.6% to 13.7% as of December 31, 2018. Significant changes in anyof these assumptions would result in a significantly higher or lower fair value measurement.Segment InformationOperating segments are identified as components of an enterprise for which separate discrete financial information is available for evaluation by the chiefoperating decision maker, or decision making group, in making decisions on how to allocate resources and assess performance. The Company views itsoperations and manages its business in one operating segment. As of December 31, 2018 and 2017, long-lived assets comprised of property and equipment of$0.3 million and $0.5 million, respectively, substantially all held in Canada.Subsequent EventsF-13Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)The Company considers events or transactions that occur after the balance sheet date, but prior to the issuance of the consolidated financial statements, toprovide additional evidence relative to certain estimates or to identify matters that require additional disclosure. Subsequent events have been evaluatedthrough the date these consolidated financial statements were issued.Net (Loss) Income Per ShareBasic net (loss) income per share is calculated by dividing net (loss) income by the weighted-average shares outstanding during the period, withoutconsideration for common stock equivalents. Diluted net (loss) income per share is calculated by adjusting weighted-average shares outstanding for thedilutive effect of common stock equivalents outstanding for the period, determined using the treasury-stock method. For purposes of the diluted net (loss)income per share calculation, stock options, unvested restricted stock, restricted stock units and warrants are considered to be common stock equivalents.The following common stock equivalents, using the treasury-stock method, were included in the calculation of diluted net (loss) income per share for theperiods indicated. Year ended December 31, 2018 2017 2016Stock options— —650,109The following common stock equivalents were excluded from the calculation of diluted net (loss) income per share for the periods indicated becauseincluding them would have had an anti-dilutive effect or the exercise prices were greater than the average market price of the common shares. Year ended December 31, 2018 2017 2016Stock options3,941,947 2,695,796 1,374,359Unvested restricted stock— 4,430 22,150Restricted stock units— — 3,333Common stock warrants9,257,632 10,055,000 926,840 13,199,579 12,755,226 2,326,682Recently Adopted Accounting StandardsIn May 2014, FASB issued Accounting Standards Update ("ASU") No. 2014-09, codified as Accounting Standards Codification ("ASC") 606, Revenue fromContracts with Customers ("ASC 606"), which supersedes all existing revenue recognition requirements, including most industry-specific guidance. The newstandard requires a company to recognize revenue when it transfers goods or services to customers in an amount that reflects the consideration that thecompany expects to receive for those goods or services. The new standard was effective on January 1, 2018 and the Company adopted this standard using themodified retrospective approach. As a result of this adoption, no amounts were recorded as a cumulative effect adjustment to accumulated deficit as ofJanuary 1, 2018.In May 2017, the FASB issued ASU No. 2017-09, Compensation-Stock Compensation (Topic 718): Scope of Modification Accounting ("ASU 2017-09").This update clarifies the changes to terms or conditions of a share-based payment award that require an entity to apply modification accounting. ASU 2017-09 is effective as of January 1, 2018. The adoption of this guidance did not have an impact on the Company's financial position, results of operations or cashflows.In November 2016, the FASB issued ASU 2016-18, Statement of Cash Flows (Topic 230): Restricted Cash. ASU 2016-18 requires that a statement of cashflows explain the change during the period in the total of cash, cash equivalents and amounts generally described as restricted cash or restricted cashequivalents. Amounts generally described as restricted cash and restricted cash equivalents should be included with cash and cash equivalents whenreconciling the beginning-of-period and end-of-period total amounts shown on the statement of cash flows. ASU 2016-18 was effective for annual andinterim periods beginning after December 15, 2017, with early adoption permitted. The Company adopted this standard effective January 1, 2018. Uponadoption of ASU 2016-18, the Company applied the retrospective transition method for each period presented and included $10,000 and $20,000 ofrestricted cash in the beginning-of-period and end-of-period cash, cash equivalents andF-14Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)restricted cash balance, respectively, in the condensed consolidated statement of cash flows for the year ended December 31, 2018. A reconciliation of cash,cash equivalents and restricted cash for each period presented is provided in Note 17 to these consolidated financial statements.On December 22, 2017, the Tax Cuts and Jobs Act (the “Act”) was enacted in the United States. The Act reduces the U.S. federal corporate tax rate from 34%to 21%, requires companies to pay a one-time transition tax on earnings of certain foreign subsidiaries that were previously tax deferred and creates new taxeson certain foreign sourced earnings. In December 2017, the SEC issued guidance under Staff Accounting Bulletin No. 118, Income Tax AccountingImplications of the Tax Cuts and Jobs Act directing taxpayers to consider the impact of the U.S. legislation as “provisional” when it does not have thenecessary information available, prepared or analyzed (including computations) in reasonable detail to complete its accounting for the change in tax law.The Company did not record any adjustments in the year ended December 31, 2018 to these provisional amounts that were material to its financialstatements. As of December 31, 2018, the Company’s accounting treatment is complete.Recently Issued Accounting PronouncementsIn February 2016, the FASB issued ASU No. 2016-02, Leases (Topic 842), or ASU 2016-02. ASU 2016-02 addresses the financial reporting of leasingtransactions. Under current guidance for lessees, leases are only included on the balance sheet if certain criteria, classifying the agreement as a capital lease,are met. This update will require the recognition of a right-of-use asset and a corresponding lease liability, discounted to the present value, for all leases thatextend beyond 12 months. For operating leases, the asset and liability will be expensed over the lease term on a straight-line basis, with all cash flowsincluded in the operating section of the statement of cash flows. For finance leases, interest on the lease liability will be recognized separately from theamortization of the right-of-use asset in the statement of operations and the repayment of the principal portion of the lease liability will be classified as afinancing activity while the interest component will be included in the operating section of the statement of cash flows. This guidance is effective for annualand interim reporting periods beginning after December 15, 2018. The Company is finalizing its implementation efforts to comply the guidance of ASU No.2016-02. Through these implementation efforts, the Company has elected to apply the package of practical expedients, the practical expedient to not applythe recognition requirements of FASB ASU No. 2016-02 to short-term leases, and the practical expedient allowing for an accounting policy election tochoose not to separate non-lease components from lease components for certain classes of assets, and instead to account for each non-lease component withits associated lease component as a single lease component. The Company did not elect to apply the hindsight practical expedient, and adopted ASU No.2016-02 on January 1, 2019 using the transition expedient. The Company estimates the right-of-use assets and lease liabilities for existing leases as ofDecember 31, 2018 to be recorded on the Company's consolidated balance sheet on January 1, 2019 to be approximately $0.1 million to $0.4 million. Noimpact is expected to the Company's consolidated statements of operations or consolidated statement of cash flows.In January 2017, the FASB issued Accounting Standards Update No. 2017-04, Simplifying the Test for Goodwill Impairment ("ASU 2017-04"). ASU 2017-04simplifies the accounting for goodwill impairment by removing Step 2 of the goodwill impairment test, which requires a hypothetical purchase priceallocation. ASU 2017-04 is effective for annual or interim goodwill impairment tests in fiscal years beginning after December 15, 2019, and should beapplied on a prospective basis. Early adoption is permitted for interim or annual goodwill impairment tests performed on testing dates after January 1, 2017.We do not expect an impact upon adoption of ASU 2017-04 on our consolidated financial statements.3. Business CombinationOn September 20, 2016, the Company entered into an agreement with Viventia Bio Inc., a corporation incorporated under the laws of the Province of Ontario,Canada (“Viventia”), the shareholders of Viventia named therein (the “Selling Shareholders”) and, solely in its capacity as seller representative, ClairmarkInvestments Ltd., a corporation incorporated under the laws of the Province of Ontario, Canada (“Clairmark”) (the “Share Purchase Agreement”), pursuant towhich the Company agreed to and simultaneously completed the acquisition of all of the outstanding capital stock of Viventia from the Selling Shareholders(the “Acquisition”). In connection with the closing of the Acquisition, the Company issued 4,013,431 shares of its common stock to the Selling Shareholders,which represented approximately 19.9% of the voting power of the Company as of immediately prior to the issuance of such shares of the Company'scommon stock. The Selling Shareholders includes Clairmark, an affiliate of one of the Company’s directors, and the Company’s CEO.F-15Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)In addition, under the Share Purchase Agreement, the Company is obligated to pay to the Selling Shareholders certain post-closing contingent cash paymentsupon the achievement of specified milestones and based upon net sales, in each case subject to the terms and conditions set forth in the Share PurchaseAgreement, including: (i) a one-time milestone payment of $12.5 million payable upon the first sale of Vicinium (the “Purchased Product”), in the UnitedStates; (ii) a one-time milestone payment of $7.0 million payable upon the first sale of the Purchased Product in any one of certain specified Europeancountries; (iii) a one-time milestone payment of $3.0 million payable upon the first sale of the Purchased Product in Japan; and (iv) and quarterly earn-outpayments equal to two percent (2%) of net sales of the Purchased Product during specified earn-out periods. Such earn-out payments are payable with respectto net sales in a country beginning on the date of the first sale in such country and ending on the earlier of (i) December 31, 2033 and (ii) fifteen years afterthe date of such sale, subject to early termination in certain circumstances if a biosimilar product is on the market in the applicable country (collectively, the"Contingent Consideration"). Under the Share Purchase Agreement, the Company, its affiliates, licensees and subcontractors are required to use commerciallyreasonable efforts, for the first seven years following the closing of the Acquisition, to achieve marketing authorizations throughout the world and, during theapplicable earn-out period, to commercialize the Purchased Product in the United States, France, Germany, Italy, Spain, United Kingdom, Japan, China andCanada. Certain of these payments are payable to individuals or affiliates of individuals that became employees or members of the Company's Board.Each of the Company, Viventia and the Selling Shareholders has agreed to customary representations, warranties and covenants in the Share PurchaseAgreement. The Share Purchase Agreement also includes indemnification obligations in favor of the Company from the Selling Shareholders, including forbreaches of representations, warranties, covenants and agreements made by Viventia and the Selling Shareholders in the Share Purchase Agreement. Inconnection with the closing of the Acquisition, the Company deposited 401,343 shares of its common stock (representing approximately 10% of theCompany's common stock portion of the aggregate closing consideration owed to the Selling Shareholders pursuant to the Share Purchase Agreement) intoan escrow fund for a period of fifteen months for the purposes of securing the indemnification obligations of the Selling Shareholders to the Company for anyand all losses for which the Company is entitled to indemnification pursuant to the Share Purchase Agreement. The Share Purchase Agreement also includesindemnification obligations in favor of the Selling Shareholders from the Company, including for breaches of representations, warranties, covenants andagreements made by the Company in the Share Purchase Agreement. During 2017, all such shares of common stock were released from escrow and deliveredto the Selling Shareholders.The Company concluded that the transaction included inputs and processes that have the ability to create outputs and accordingly accounted for thetransaction as a business combination in accordance with ASC 805. As such, the assets acquired and liabilities assumed were recorded at fair value, with theremaining purchase price recorded as goodwill.The purchase price consisted of the issuance of the 4,013,431 shares of the Company's common stock to the Selling Shareholders and the fair value of theContingent Consideration.The Company valued the shares issued at $13.5 million, based on the closing price of the Company's common stock on September 20, 2016 (the“Acquisition Date”). The Contingent Consideration was preliminarily valued at $46.2 million, using a probability-adjusted, discounted cash flow estimate asof the Acquisition Date. The total fair value of consideration for the acquisition was $59.7 million.The Company finalized its purchase accounting for the Acquisition during the third quarter of 2017 based on the best estimates of the Company. Theconsideration for the Acquisition and the final allocation of the purchase consideration presented was updated to reflect new information related to facts andcircumstances which existed as of the Acquisition Date. The changes in assumptions were primarily due to additional information gathered regarding thepotential market for Vicinium outside of the U.S., which resulted in adjustments to the fair value of contingent consideration as of the Acquisition Date andthe in-process research and development assets for Vicinium in the European Union ("E.U.") and the rest of world. The assumptions related to the U.S. marketwere not updated as sufficient information had previously been gathered to support this estimate. The update of these assumptions also had an effect on thediscount rate and certain other valuation assumptions used to value the acquired assets due to an adjustment in the Company specific risk factors, whicheffected the in-process research and development assets for Vicinium in the U.S., E.U., and the rest of world. As a result of these changes, the Companyupdated (1) the fair value of the in-process research and development assets for Vicinium, which resulted in a reduction in the fair value of the in-processresearch and development asset for Vicinium in the rest of the world to a de minimus amount, (2) the fair value of the contingent consideration, and (3) therelated deferred tax liability and goodwill.F-16Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)The preliminary estimate of the purchase price and the final purchase price as of the Acquisition Date are reflected in the following table (in thousands): Preliminary Fair Valueof Consideration as ofDecember 31, 2016 Adjustment Final Fair Value ofConsiderationShares Issued$13,525 $— $13,525Contingent Consideration46,200 (14,600) 31,600 $59,725 $(14,600) $45,125The preliminary allocation of the purchase consideration and the final allocation of the purchase consideration as of the Acquisition Date are reflected in thefollowing table (in thousands): PreliminaryAllocation as ofDecember 31, 2016 Adjustment Final AllocationCash and cash equivalents$136 $— $136Prepaid expenses and other assets1,162 — 1,162Property and equipment867 — 867In-process research and development assets (all markets)60,500 (14,100) 46,400Goodwill16,864 (3,800) 13,064Accounts payable(1,163) — (1,163)Accrued expenses(1,494) (507) (2,001)Other liabilities(812) — (812)Deferred tax liability(16,335) 3,807 (12,528) $59,725 $(14,600) $45,125The revised fair values of indefinite-lived intangible assets, deferred tax liability and goodwill noted above did not have an impact on the Company’sconsolidated statement of operations and comprehensive (loss) income, as the effected assets are not amortized. The Company is required to revalue itscontingent consideration at each balance sheet date. As such, changes in the fair value of contingent consideration since the Acquisition Date due to updatedassumptions and estimates are recognized within the consolidated statements of operations and comprehensive (loss) income.The deferred tax liability of $12.5 million primarily relates to the potential future impairments or amortization associated with IPR&D intangible assets,which is not deductible for tax purposes, and which cannot be used as a source of income to realize deferred tax assets. As a result, the Company recorded thedeferred tax liability with an offset to goodwill.The amount allocated to the IPR&D is considered to be indefinite-lived until the completion or abandonment of the associated research and developmentefforts. As of December 31, 2018, there was no impairment related to the IPR&D.The Company allocated the excess of the purchase price over the identifiable intangible assets to goodwill. Such goodwill is not deductible for tax purposesand represents the value placed on expected synergies and deferred tax liabilities recognized in connection with the Acquisition. As of December 31, 2018,there was no impairment of goodwill. All goodwill has been assigned to the Company’s single reporting unit.These fair value measurements were based on significant inputs not observable in the market and thus represent Level 3 fair value measurements.F-17Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)The operating results of Viventia for the period from September 20, 2016 to December 31, 2016, which includes no revenue and an operating loss of $3.5million, have been included in the Company’s consolidated financial statements as of and for the year ended December 31, 2016.The Company incurred a total of $2.5 million in transaction costs in connection with the transaction, excluding Viventia transaction costs, which wereincluded in general and administrative expense within the consolidated statements of operations and other comprehensive income (loss) for the year endedDecember 31, 2016.The Company’s financial results for the year ended December 31, 2016 are inclusive of Viventia financial results since the Acquisition Date. The unauditedestimated pro forma results presented below include the effects of the Acquisition as if it had been consummated as of the beginning of each period. The proforma results include the direct expenses of Viventia as well as the additional depreciation expense as a result of the increase in the fair value of the fixedassets. The pro forma results exclude the costs of the transaction, severance and stock-based compensation expenses, the Viventia forgiveness of debt and therelated interest expense in connection with the Acquisition. In addition, the pro forma results do not include any anticipated synergies or other expectedbenefits of the Acquisition. Accordingly, the unaudited estimated pro forma financial information below is not necessarily indicative of either future resultsof operations or results that might have been achieved had the Acquisition been consummated as of the beginning of each period (in thousands): Year Ended December 31, 2016Revenue$29,981Net loss(3,026)4. Collaboration AgreementOn May 28, 2013, the Company entered into the collaboration and license agreement (the "Collaboration and License Agreement") with ThromboGenicsN.V. ("ThromboGenics"). Under the Collaboration and License Agreement, the Company and ThromboGenics collaborated to seek to identify protein orpeptide therapeutics that directly modulate any of a specified set of targets in a novel pathway in retinal disease.ThromboGenics funded certain research and development services performed by the Company during the research term, which was initially thirty (30)months and automatically extended to the extent that the parties mutually agreed in writing. The initial research term concluded in November 2015, howeverit was amended at that time to extend the performance period into 2016. The Collaboration and License Agreement provided for potential future payments tothe Company upon achievement of specified pre-clinical, clinical and regulatory milestones with respect to collaboration products and royalties on sales ofcollaboration products by ThromboGenics, its affiliates or sublicensees. However, as there have not been any collaboration products identified whosemodulation of any of the targets has been confirmed in the course of the research conducted under the Collaboration and License Agreement, none of thesemilestones or royalties were payable. On August 1, 2016, the Company received notice from ThromboGenics of its termination, effective as of October 31,2016, of the Collaboration and License Agreement.The Company accounted for this agreement pursuant to ASC Topic 605-25. The Company received a $1.75 million upfront payment and subsequentpayments to perform activities under the Collaboration and License Agreement at a set rate per full-time equivalent person working on collaborationactivities. The Company was recognizing the arrangement consideration using the proportional performance method, by which the amounts were recognizedin proportion to the costs incurred based on full time equivalent personnel efforts. Subsequent to the amendment in November 2015, the Company wasrecognizing revenue on a straight-line basis over the remaining performance period. The Company recorded revenue of $0.4 million for the year endedDecember 31, 2016. No revenue was recorded for the years ended December 31, 2018 and 2017. No further amounts are expected to be recognized in thefuture related to this arrangement. The costs incurred by the Company related to the research activities were recorded as research and development expense inthe consolidated statement of operations and comprehensive (loss) income.5. License Agreement with RocheF-18Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)On June 10, 2016, the Company entered into the License Agreement with F. Hoffmann-La Roche and Hoffmann La-Roche Inc. (collectively, "Roche"), whichbecame effective on August 16, 2016 (the "License Agreement"). Under the License Agreement, the Company granted Roche an exclusive, worldwidelicense, including the right to sublicense, to its patent rights and know-how related to the Company’s monoclonal antibody EBI-031 or any other IL-6antagonist anti-IL-6 monoclonal antibody, to make, have made, use, have used, register, have registered, sell, have sold, offer for sale, import and export anyproduct containing such an antibody or any companion diagnostic used to predict or monitor response to treatment with such a product (collectively, the“Licensed Intellectual Property”).Under the License Agreement, Roche is required to continue developing EBI-031 and any other product made from the Licensed Intellectual Property thatcontains an IL-6 antagonist anti-IL-6 monoclonal antibody (a “Licensed Product”), and pursue ongoing patent prosecution, at its cost.Financial TermsThe Company received an upfront license fee of $7.5 million from Roche and Roche agreed to pay up to an additional $262.5 million upon the achievementof specified regulatory, development and commercial milestones with respect to up to two unrelated indications. Specifically, an aggregate amount of up to$197.5 million is payable to the Company for the achievement of specified milestones with respect to the first indication: $72.5 million in developmentmilestones, $50.0 million in regulatory milestones and $75.0 million in commercialization milestones. Additional amounts of up to $65.0 million arepayable upon the achievement of specified development and regulatory milestones in a second indication.The first development milestone payment for the first indication was paid in the amount of $22.5 million as a result of the Investigational New Drug ("IND")application for EBI-031 becoming effective on or before September 15, 2016.In addition, the Company is entitled to receive royalty payments in accordance with a tiered royalty rate scale, with rates ranging from 7.5% to 15% for netsales of potential future products containing EBI-031 and up to 50% of these rates for net sales of potential future products containing other IL-6 compounds,with each of the royalties subject to reduction under certain circumstances and to the buy-out options of Roche further described below.Buy-Out OptionsThe License Agreement provides for two “option periods” during which Roche may elect to make a one-time payment to the Company and, in turn, terminateits diligence, milestone and royalty payment obligations under the License Agreement. Specifically, (i) Roche may exercise a buy-out option following thefirst dosing (“Initiation”) in the first Phase 2 study for a Licensed Product until the day before Initiation of the first Phase 3 study for a Licensed Product, inwhich case Roche is required to pay the Company $135.0 million within 30 days after Roche's exercise of such buy-out option and receipt of an invoice fromthe Company, or (ii) Roche may exercise a buy-out option following the day after Initiation of the first Phase 3 study for a Licensed Product until the daybefore the acceptance for review by the U.S. Food and Drug Administration ("FDA") or other regulatory authority of a biologics license application (“BLA”)or similar application for marketing approval for a Licensed Product in either the United States or in the E.U., in which case Roche is required to pay theCompany, within 30 days after Roche’s exercise of such buy-out option and receipt of an invoice from the Company, $265.0 million, which amount wouldbe reduced to $220.0 million if none of the Company’s patent rights containing a composition of matter claim covering any compound or Licensed Producthas issued in the E.U.TerminationThe Company or Roche may each terminate the License Agreement if the other party breaches any of its material obligations under the License Agreementand does not cure such breach within a specified cure period. Roche may terminate the License Agreement following effectiveness by providing advancewritten notice to the Company or by providing written notice if the Company is debarred, disqualified, suspended, excluded, or otherwise declared ineligiblefrom certain federal or state agencies or programs. The Company may terminate the License Agreement if, prior to the first filing of a BLA for a LicensedProduct, there is a period of 12 months where Roche is not conducting sufficient development activities with respect to the products made from the LicensedIntellectual Property.The Company’s License Agreement with Roche contains the following deliverables: 1) an exclusive, worldwide license, including the right to sublicense, toits patent and know-how related to the Company’s monoclonal antibody EBI-031 or anyF-19Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)other IL-6 antagonist anti-IL-6 monoclonal antibody; 2) IND regulatory clearance activities; 3) conduct a tissue cross-reactivity study; 4) transfer pre-clinicalinventory and 5) perform de minimus post-effective date services.The Company has determined that the License Agreement contains four units of accounting. The de minimis post-effective date services were not determinedto be substantive, and thus were not considered units of accounting. The $29.9 million of allocable arrangement consideration was allocated to each of theunits of accounting using the relative selling price method based on the Company’s best estimate of selling price of each of the units of accounting. The bestestimate of selling price of the license was calculated using a discounted cash flow model that included the following key assumptions: the developmenttimeline of EBI-031, future revenue forecast for EBI-031, and an appropriate discount rate to discount the related cash flows and probability of successfuldevelopment. The best estimate of selling price of the remaining deliverables was based on estimated costs plus a reasonable margin. The allocation ofarrangement consideration was not particularly sensitive to changes in the Company's best estimate of selling price given the significant value ascribed to thelicense deliverable.During 2016, the basic revenue recognition criteria was met for all units of accounting except for the transfer of pre-clinical inventory and the Companyrecognized $29.6 million in revenue. During 2017, the Company transferred the remaining pre-clinical inventory to Roche and accordingly, recognized $0.4million in revenue related to the License Agreement.The License Agreement is subject to the provisions of ASC 606, which was adopted effective January 1, 2018 utilizing a modified retrospective method. TheCompany concluded that all performance obligations had been achieved as of the adoption date and therefore the full transaction price was consideredearned. The transaction price was determined to be the$30.0 million received in 2016. Additional consideration to be paid to the Company upon theachievement of certain milestones will be included if it is expected that the amounts will be received and the amounts would not be subject to a constraint.As of the date of the adoption, no amounts were expected to be received from the achievement of any milestones due to the nature of the milestones and thedevelopment status of the product candidates at the time of the adoption. As a result, there were no amountsrequired to be recorded as a cumulative adoption adjustment as the consideration recognized under ASC 606 was consistent with the amounts recognizedunder the previous accounting literature.As of December 31, 2018, the Company concluded that there would be no adjustments to the transaction price as the Company continued to not expect anyamounts to be received from any milestones within the License Agreement. This is due to the nature of the milestones and the development status of theproduct candidates at the time of the adoption. As a result, no revenue was recognized during the year ended December 31, 2018 as all performanceobligations had been previously achieved and there was no change in the transaction price during the period. No revenue would have been recognized underthe previous accounting literature as no milestones were achieved in the period, which was the revenue recognition criteria under the previous accountingliterature.6. Property and EquipmentProperty and equipment and related accumulated depreciation are as follows (in thousands): Estimated UsefulLife (Years) December 31, 2018 2017Lab equipment5 $443 $443Furniture and fixtures4 16 16Computer equipment3 80 73Software3 28 28Leasehold improvementsLesser of useful life or remaininglease term 293 293 860 853Less accumulated depreciation and amortization (539) (331)Total property and equipment, net $321 $522Depreciation expense amounted to $208,000, $285,000 and $178,000 for the years ended December 31, 2018, 2017 and 2016, respectively. During the yearsended December 31, 2018 and 2017, the Company disposed/sold property and equipment with aF-20Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)net book value of $0 and $0, respectively, for proceeds of $5,000 and $98,000, respectively. During the years ended December 31, 2018 and 2017, theCompany purchased equipment for $7,000 and $10,000, respectively.7. Accrued ExpensesAccrued expenses consisted of the following (in thousands): December 31, 2018 2017Development costs$2,928 $2,581Employee compensation (including reduction in workforce)1,045 735Severance to former CEO278 —Professional fees464 463Other3134 $4,746 $3,8138. IndebtednessTerm LoanOn March 1, 2016, the Company prepaid all outstanding amounts owed to SVB under the amended Loan Agreement. These obligations included theoutstanding principal and interest of $13.8 million and a prepayment penalty of $0.2 million. In addition, the Company was required to pay a final paymentequal to 6% of the amounts borrowed under the amended Loan Agreement, or $0.9 million, of which $0.4 million was accrued as of March 1, 2016. Inaddition, as a result of the prepayment, the Company wrote off the unamortized debt issuance costs and debt discount of $0.2 million. In connection with theprepayment, the Company recorded a loss on extinguishment of debt of $0.9 million, which is included in other income (expense) on the consolidatedstatements of operations and comprehensive income (loss) for the year ended December 31, 2016.9. Commitments and ContingenciesOperating LeasesThe Company leases a manufacturing facility located in Winnipeg, Manitoba Canada, which consists of an approximately 31,100 square foot manufacturing,laboratory, warehouse and office facility, under a five year renewable lease through September 2020 with a right to renew the lease for one subsequent five-year term. The minimum monthly rent under this lease is approximately $12,400 per month. We also expect to incur approximately $13,300 in relatedoperating expenses per month. Rent expense under this lease, including the related operating costs, was $297,000 for the year ended December 31, 2018,$320,000 for the year ended December 31, 2017 and $86,000 for the period beginning on the Acquisition Date through December 31, 2016.The Company leased its former corporate headquarters in Cambridge, Massachusetts under an operating lease that was scheduled to expire on April 30, 2018.On October 14, 2016, the Company and the landlord mutually agreed to terminate the lease and voluntarily surrender the premises. The Company recorded$565,000 in rent expense for the year ended December 31, 2016 for this lease.The Company leases its current corporate headquarters in Cambridge, Massachusetts under a lease that was originally executed in October 2016, and wasrenewed in December 2018 for a term of four months. The minimum monthly rent for this office space is approximately $10,000 per month. The Companyrecorded $148,000 in rent expense for the year ended December 31, 2018 for this lease.The Company leased office space in Willow Grove, PA, where it occupied office space under a one-year lease that was executed in May 2017 and terminatedin April 2018. The minimum monthly rent under this lease was approximately $2,200 per month. The Company recorded approximately $9,000 in rentexpense for the year ended December 31, 2018 for this lease.The Company leases office space in Philadelphia, PA, where it occupies office space under a lease that was executed in December 2017 and had an initialterm of six months. The lease has been amended several times and currently the termF-21Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)extends through August 2019. Currently, the minimum monthly rent under this lease is approximately $20,500 per month. The Company recorded $179,000in rent expense for the year ended December 31, 2018 for this lease.The minimum aggregate future lease commitment at December 31, 2018 is as follows (in thousands): 2019 (1)$29520201072021— $402(1) We canceled certain leases effective March 31, 2019 and therefore no amounts have been included subsequent to that date.The Company also occupies office space in Toronto, Ontario, Canada with rent of approximately $2,000 per month, on a month-to-month lease, which can beterminated by either party by giving 30 days written notice. These payments are not included in the minimum aggregate future lease commitments above.This lease was terminated in December 2018 with an effective termination date of December 31, 2018.In February 2016, the FASB issued ASU 2016-02 which addresses the financial reporting of leasing transactions. Under current guidance for lessees, leasesare only included on the balance sheet if certain criteria, classifying the agreement as a capital lease, are met. This update will require the recognition of aright-of-use asset and a corresponding lease liability, discounted to the present value, for all leases that extend beyond 12 months. For operating leases, theasset and liability will be expensed over the lease term on a straight-line basis, with all cash flows included in the operating section of the statement of cashflows. For finance leases, interest on the lease liability will be recognized separately from the amortization of the right-of-use asset in the statement ofoperations and the repayment of the principal portion of the lease liability will be classified as a financing activity while the interest component will beincluded in the operating section of the statement of cash flows. This guidance is effective for annual and interim reporting periods beginning after December15, 2018. The Company is finalizing its implementation efforts to comply the guidance of ASU No. 2016-02. Through these implementation efforts, theCompany has elected to apply the package of practical expedients, the practical expedient to not apply the recognition requirements of FASB ASU No. 2016-02 to short-term leases, and the practical expedient allowing for an accounting policy election to choose not to separate non-lease components from leasecomponents for certain classes of assets, and instead to account for each non-lease component with its associated lease component as a single leasecomponent. The Company did not elect to apply the hindsight practical expedient, and will adopt ASU No. 2016-02 on January 1, 2019 using the transitionexpedient. The Company estimates the right-of-use assets and lease liabilities for existing leases as of December 31, 2018 to be recorded on its consolidatedbalance sheet on January 1, 2019 to be approximately $0.1 million to $0.4 million. No impact is expected to its consolidated statements of operations or itsconsolidated statement of cash flows.License AgreementsThe Company is a party to or assignee of license agreements that may require it to make future payments relating to license fees, sublicense fees, milestonefees, and royalties on future sales of licensed products.The following outlines the license agreements the Company believes it will owe payments under if its product candidates reach certain milestones and beginto generate revenue.The Schepens Eye Research Institute, Inc. / The Massachusetts Eye and Ear InfirmaryIn July 2010, the Company entered into a license agreement with The Schepens Eye Research Institute, Inc. (“Schepens”), pursuant to which Schepensgranted the Company an exclusive royalty-bearing license, with the right to grant sublicenses, to certain intellectual property rights for the development ofIL-1blocker for ophthalmic indications. The Company is obligated to pay Schepens up to $4.7 million and issue up to 105,000 shares of its common stock inmilestone payments, contingent upon the issuance of certain patents. In addition, the Company is obligated to pay Schepens a tiered single-digit royaltybased on net sales of the licensed product. During the year ended December 31, 2014, the Company paid Schepens and expensed $350,000 upon theachievement of a clinical milestone. On February 10, 2016, the Company provided notice to Schepens of the Company’s termination of the licenseagreement, which termination was effective 60 days following receipt of such notice by Schepens.F-22Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)The University of ZurichThe Company has an exclusive license agreement with the University of Zurich ("Zurich"), which grants the Company an exclusive license, with the right tosublicense, to make, have made, use and sell under certain patents primarily directed to the Company's targeting agent, including EpCAM chimera, andrelated immunoconjugates and methods of use and manufacture of the same. These patents cover some key aspects of the Company’s product candidateVicinium. The Company is obligated to pay $750,000 in milestone payments for its first product candidate in the event it reaches the applicable clinicaldevelopment milestones. As part of the consideration, the Company is also obligated to pay up to a 4% royalty on the net product sales for any products thatare covered by the applicable Zurich patent rights. The Company has the right to reduce the amount of royalties owed to Zurich if the total royalty rate owedby the Company to Zurich and any other third party is 10% or greater, provided that the royalty rate may not be less than 2% of net sales. The obligation topay royalties in a particular country expires upon the expiration, lapse or abandonment of the last of the Zurich patent rights that covers the manufacture, useor sale of a product and there is no obligation to pay royalties in a country if there is no patent rights that cover the manufacture, use or sale of a product.License Agreement with MicrometThe Company has a license agreement with Micromet AG, or Micromet, now part of Amgen, Inc., which grants it nonexclusive rights, with certain sublicenserights, for know-how and patents allowing exploitation of certain single chain antibody products. These patents cover some key aspects of Vicinium. Underthe terms of the agreement, the Company may be obligated to pay up to €3.6 million in milestone payments, for the first product candidate that achievesapplicable clinical development milestones. Based on current clinical status, the Company anticipates that certain of these milestones may be triggered byVicinium’s clinical development pathway. The Company is also required to pay up to a 3.5% royalty on the net sales for products covered by the agreement,which includes Vicinium. The royalty rate owed to Micromet in a particular country will be reduced to 1.5% if there are no valid claims covering the productin that country. The obligation to pay royalties in a particular country expires upon the later of the expiration date of the last valid claim covering theproduct and the tenth anniversary of the first commercial sale of the product in such country. Finally, the Company is required to pay to Micromet an annuallicense maintenance fee of €50,000, which can be credited towards any royalty payment we owe to Micromet.License Agreement with XOMAThe Company has a license agreement with XOMA Ireland Limited, or XOMA, which grants it non-exclusive rights to certain XOMA patent rights and know-how related to certain expression technology, including plasmids, expression strains, plasmid maps and production systems. These patents and related know-how cover some key aspects of Vicinium. Under the terms of the agreement, the Company is required to pay up to $250,000 in milestone payments for aproduct candidate that incorporates know-how under the license and achieves applicable clinical development milestones. Based on current clinical status,the Company anticipates that these milestones may be triggered by Vicinium’s clinical development pathway. The Company is also required to pay a 2.5%royalty on the net sales for products incorporating XOMA’s technology, which includes Vicinium. The Company has the right to reduce the amount ofroyalties owed to XOMA on a country-by-country basis by the amount of royalties paid to other third parties, provided that the royalty rate to XOMA maynot be less than 1.75% of net sales. In addition, the foregoing royalty rates are reduced by 50% with respect to products that are not covered by a valid patentclaim in the country of sale. The obligation to pay royalties in a particular country expires upon the later of the expiration date of the last valid claimcovering the product and the tenth anniversary of the first commercial sale of the product in such country. Merck KGaAThe Company holds an exclusive license agreement with Merck KGaA ("Merck") pursuant to which the Company was granted an exclusive license, with theright to sublicense, under certain patents and technology relating to aspects of VB6-845d, to make, use, sell and import VB6-845d or any products that wouldotherwise infringe such patents in the field of therapeutic or diagnostic purposes in humans. Under the agreement, the Company may be obligated to makemilestone payments in respect of certain stages of regulatory approval reached by a product candidate generated by this technology or covered by a licensedpatent including: (a) $2,000,000 upon the start of the first Phase 3 clinical trial for a licensed product; (b) $2,000,000 upon submission of the first BiologicsLicense Application ("BLA") for a licensed product; (c) $2,000,000 upon the approval of the first BLA in certain countries for a licensed product and$1,000,000 upon each of the second and third approvals of a BLA in certain additional countries for the same licensed product (total of $4,000,000); and (d)$2,000,000 upon the approval of the second BLA in certain countries for a licensed product; and $1,000,000 upon each of the second and third approvals ofthe second BLA in certain additional countries for the same licensed product (total of $4,000,000). The Company may be obligated to pay a 1.5% royalty onthe net product sales up to $150,000,000 and a 2% royalty on the net product sales above such amount.F-23Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)The license remains in force on a country-by-country basis and product-by-product basis, and expires at the longer of (i) the expiration of the last to expirepatent within the licensed patent rights that covers a licensed product and (ii) 10 years from the first commercial sale of a licensed product in such country;provided that no royalty is payable for more than 15 years from the first commercial launch of a licensed product anywhere in the world.Legal ContingenciesThe Company does not currently have any contingencies related to ongoing legal matters.10. Common StockThe voting dividend and liquidation rights of holders of shares of common stock are subject to and qualified by the rights, powers and preferences of theholders of the shares of preferred stock. The Company’s common stock has the following characteristics:VotingThe holders of common stock shall have voting rights at all meetings of stockholders, each such holder being entitled to one vote for each share thereof heldby such holder; provided, however, that, except as otherwise required by law, holders of common stock shall not be entitled to vote on any amendment to theCompany’s certificate of incorporation that relates solely to the terms of one or more outstanding series of preferred stock if the holders of such affected seriesare entitled, either separately or together as a class with the holders of one or more such series, to vote thereon. There shall be no cumulative voting.DividendsDividends may be declared and paid on the common stock from funds lawfully available thereof as and when determined by the Board and subject to anypreferential dividend or other rights of any then outstanding preferred stock.LiquidationUpon the dissolution or liquidation of the Company, whether voluntary or involuntary, holders of common stock will be entitled to receive all assets of theCompany available for distribution to its stockholders, subject to any preferential or other rights of any then outstanding preferred stock.Reserved for Future IssuanceThe Company has reserved the following shares of common stock: As of December 31, 2018 2017Unvested restricted stock— 4,430Options to purchase common stock5,942,884 3,879,535Warrants to purchase common stock9,257,632 10,055,000Employee stock purchase plan38,469 59,461 15,238,985 13,998,426Secondary Public OfferingsOn November 1, 2017, the Company raised approximately $7.0 million of net proceeds from the sale of 5,525,000 units (each unit consisting of one share ofcommon stock and one common warrant to purchase one share of common stock) and 4,475,000 pre-funded units (each pre-funded unit consisting of one pre-funded warrant to purchase one share of common stock and one common warrant to purchase one share of common stock) at a purchase price of $0.80 per unitand $0.79 per pre-funded unit (the "November 2017 Financing"). Each common warrant contained in a unit or pre-funded unit has an exercise price of $0.80per share and is exercisable immediately and will expire five years from the date of issuance. Each pre-funded warrantF-24Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)contained in a pre-funded unit was exercisable for one share of common stock and the exercise price was $0.01 per share. As of December 31, 2018, theCompany had issued 4,475,000 shares of the Company’s common stock pursuant to the exercise of all of the pre-funded warrants sold in connection with theNovember 2017 Financing.Equity FinancingsOn March 23, 2018, the Company raised approximately $9.0 million of net proceeds from the sale of 7,968,128 shares of common stock at a priceof $1.13 per share in a registered direct offering and the sale of common stock purchase warrants to purchase 7,968,128 shares of common stock at a priceof $0.125 for each warrant to purchase one share of common stock in a concurrent private placement (collectively, the “March 2018 Financing”). Subject tocertain ownership limitations, the common stock purchase warrants issued in the March 2018 Financing were exercisable immediately upon issuance at anexercise price equal to $1.20 per share of common stock, subject to adjustments as provided under the terms of such common stock purchase warrants. Thecommon stock purchase warrants are exercisable for five years from March 23, 2018.On June 4, 2018, the Company raised approximately $41.9 million of net proceeds from the sale of 25,555,556 shares of its common stock at a priceof $1.80 per share in an underwritten public offering (the “June 2018 Financing”).In addition, the Company received proceeds of $7.3 million from the issuance of 8,765,496 shares of its common stock upon the cash exercise of commonstock purchase warrants issued in connection with (i) its underwritten public offering in November 2017 Financing and (ii) its private placement of commonstock purchase warrants in the March 2018 Financing during the year ended December 31, 2018.11. Common Stock WarrantsOn November 25, 2014, the Company issued the Warrants to purchase a total of 27,500 shares of common stock to SVB and Life Science Loans, LLC at anexercise price of $11.04 per share in connection with the Second Loan Modification Agreement (See Note 8). In connection with the Company's drawdown ofan additional $5.0 million pursuant to the Loan Agreement in May 2015, the Warrants automatically became exercisable for the purchase of an additional27,500 shares of common stock at a per share exercise price of $11.83. The Warrants are exercisable immediately and have a ten-year life. The Warrants wereinitially valued at $0.3 million each using the Black-Scholes option-pricing model. As of December 31, 2018, all 55,000 warrants remain un-exercised.On December 2, 2014, the Company issued warrants to purchase 871,840 shares of common stock at an exercise price of $15.00 per share in connection witha private placement of common stock (the "PIPE Warrants"). The PIPE Warrants were exercisable immediately and had a three-year life. Upon certain events,the Company was required to settle the PIPE Warrants for cash. As a result, the Company had classified the PIPE Warrants as a liability. The PIPE Warrantsexpired un-exercised in December 2017.The Company allocated $3.0 million to the PIPE Warrants with the residual proceeds allocated to the common stock. The fair value of the PIPE Warrants wasdetermined using the Black-Scholes option pricing model. The fair value of the PIPE Warrants was re-measured at each reporting date using then-currentassumptions with changes in fair value charged to other income (expense) on the statements of operations and comprehensive (loss) income. The followingassumptions were used in valuing the PIPE Warrants: December 31,2016Risk-free interest rate0.85%Expected dividend yield—%Expected term (in years)0.92Expected volatility83.39%On November 1, 2017, the Company issued warrants (the "November 2017 Warrants") to purchase a total of 10,000,000 shares of common stock at anexercise price of $0.80 per share. Each of the November 2017 Warrants is exercisable immediately and will expire five years from the date of issuance. Thewarrants were concluded to be equity classified and recorded to Additional Paid-in Capital. As of December 31, 2018, a total of 1,991,687 warrants remainun-exercised.F-25Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)On March 23, 2018, the Company issued warrants to purchase a total of 7,968,128 shares of common stock at an exercise price of $1.20 per share. Each of theMarch 2018 Warrants were purchased at a price of $0.125 per warrant and, subject to certain ownership limitations, the common stock purchase warrantsissued were exercisable immediately upon issuance at an exercise price of $1.20 per share of common stock. The warrants were concluded to be equityclassified and recorded to Additional Paid-in Capital. The common stock warrants are exercisable for five years from March 23, 2018. As of December 31,2018, a total of 7,210,945 remain un-exercised.12. Share-Based Payments2009 Stock Incentive PlanThe Company maintains the Sesen Bio, Inc. 2009 Stock Incentive Plan (the “2009 Plan”), as amended and restated, for employees, directors, consultants, andadvisors to the Company. Upon the closing of the Company’s IPO in February 2014, the Company ceased granting stock incentive awards under the 2009Plan. The 2009 Plan provided for the grant of incentive and non-qualified stock options and restricted stock grants as determined by the Board. Under the2009 Plan, stock options could not be granted at less than fair value on the date of the grant. Furthermore, the exercise price of incentive stock optionsgranted to an employee, who, at the time of grant, is a 10% shareholder, could not be less than 110% of the fair value on the date of grant.Terms of stock option agreements, including vesting requirements, are determined by the Board, subject to the provisions of the 2009 Plan. Options andrestricted stock awards granted by the Company generally vest ratably over four years, with a one-year cliff for new employee awards, and are exercisablefrom the date of grant for a period of ten years. Restricted stock issuances and early exercises of stock options are subject to the Company’s right ofrepurchase at the original issuance price, which right lapses over the vesting period of the stock. For options and restricted stock awards granted to date, theexercise price equaled the estimated fair value of the common stock as determined by the Board on the date of grant.2014 Stock Incentive PlanIn December 2013, the Company’s 2014 Stock Incentive Plan (the “2014 Plan”) was adopted by the Board and was approved by the Company’s stockholdersin January 2014. The 2014 Plan became effective immediately prior to the closing of the Company’s IPO in February 2014. The 2014 Plan provides for thegrant of incentive stock options, nonstatutory stock options, restricted stock awards, restricted stock units, stock appreciation rights and other stock-basedawards. The number of shares of the Company’s common stock reserved for issuance under the 2014 Plan is the sum of (1) 708,661 shares, plus (2) the numberof shares (up to 1,347,821 shares) equal to (a) 1,586 shares (representing the number of shares reserved for issuance under the 2009 Plan that remainedavailable for future issuance as of the effectiveness of the 2014 Plan) and (b) the number of shares of the Company’s common stock subject to outstandingawards under the Company’s 2009 Plan that expire, terminate or are otherwise surrendered, cancelled, forfeited or repurchased without having been fullyexercised or resulting in any common stock being issued, plus (3) an annual increase, to be added on the first day of each fiscal year, equal to the lowest of1,102,362 shares of the Company’s common stock, 4% of the number of shares of the Company’s common stock outstanding on the first day of theapplicable fiscal year and an amount determined by the Company’s Board. On January 1, 2018, the Company increased the number of shares reserved forissuance under the 2014 Plan by 1,102,362 shares. As of December 31, 2018, the total number of shares of common stock available for grant under the 2014Plan was 2,000,937.The Company’s employees, officers, directors, consultants and advisors are eligible to receive awards under the 2014 Plan. However, incentive stock optionsmay only be granted to the Company’s employees.Inducement GrantsOn September 20, 2016, in connection with the Acquisition, the Company granted stock options to purchase 650,000 shares of the Company's commonstock. The grants were made in the form of inducement equity awards outside the 2014 Plan in accordance with Nasdaq Listing Rule 5635(c)(4).These stock options were granted with an effective grant date of September 20, 2016 and an exercise price of $3.37 per share (the closing price per share ofthe Company's common stock on September 20, 2016) as an inducement to each recipient in connection with his employment. The inducement equityawards were approved and recommended by the Company's Compensation Committee, approved by the Board and were made as an inducement material toeach recipient's acceptance of employment with the Company in accordance with Nasdaq Listing Rule 5635(c)(4). Effective as of August 7, 2018, Stephen A.F-26Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)Hurly departed as the President and Chief Executive of the Company. In connection with his departure, a total of 350,000 inducement equity awardspreviously granted to Mr. Hurly were cancelled during the year ended December 31, 2018.On August 7, 2018, in connection with the Company’s hiring of Dr. Cannell as the Company’s Chief Executive Officer, the Company granted Dr. Cannellstock options to purchase 1,350,000 shares of the Company's common stock. The grants were made in the form of inducement equity awards outside the 2014Plan in accordance with Nasdaq Listing Rule 5635(c)(4). Dr. Cannell’s stock option was granted with an effective grant date of August 7, 2018 and anexercise price of $1.60 per share (the closing price per share of the Company's common stock on August 7, 2018) as an inducement to Dr. Cannell inconnection with his employment. The inducement equity award was approved and recommended by the Company's Compensation Committee, approved bythe Board and were made as an inducement material to Dr. Cannell's acceptance of employment with the Company in accordance with Nasdaq Listing Rule5635(c)(4).On December 3, 2018, in connection with the Company’s hiring of Dennis Kim, M.D., MPH as the Company’s Chief Medical Officer, the Company grantedDr. Kim stock options to purchase 425,000 shares of the Company's common stock. The grants were made in the form of inducement equity awards outsidethe 2014 Plan in accordance with Nasdaq Listing Rule 5635(c)(4). Dr. Kim’s stock option was granted with an effective grant date of December 3, 2018 andan exercise price of $1.70 per share (the closing price per share of the Company's common stock on December 3, 2018) as an inducement to Dr. Kim inconnection with his employment. The inducement equity award was approved and recommended by the Company's Compensation Committee, approved bythe Board and were made as an inducement material to Dr. Kim’s acceptance of employment with the Company in accordance with Nasdaq Listing Rule5635(c)(4).Each of the inducement grants expires on the day preceding the tenth anniversary of the grant date and vests over four years, with 25% of the original numberof shares subject to the option vesting on the one year anniversary of the date of grant of the option and an additional 6.25% of the shares subject to theoption vesting at the end of each successive three-month period following the one -year anniversary of the date of grant of the option, subject to therecipient's continued service with the Company through the applicable vesting dates.As of December 31, 2018, the total amount of shares outstanding classified as inducement awards was 1,975,000.A summary of the Company’s stock option activity and related information follows: Shares Weighted-AverageExercise Price RemainingContractual Life(in years)AggregateIntrinsicValue(in thousands)Outstanding at December 31, 20172,695,796 $3.16 8.55$146Granted3,545,900 1.71 Exercised(439,013) 0.62 Cancelled or forfeited(1,860,736) 3.21 Outstanding at December 31, 20183,941,947 $2.12 9.14$57Exercisable at December 31, 2018938,968 $3.30 8.04$1The total intrinsic value of options exercised for the years ended December 31, 2018, 2017 and 2016 was $490,000, $258,000, $942,000, respectively. Thetotal fair value of employee options vested for the years ended December 31, 2018, 2017 and 2016 was $1.3 million, $1.1 million, and $3.7 million,respectively.Restricted StockFrom time to time, upon approval by the Board, certain employees and advisors have been granted restricted shares of common stock. Certain shares ofrestricted stock were subject to repurchase rights. Accordingly, the Company recorded the proceeds from the issuance of certain restricted stock as a liabilityin the consolidated balance sheets. The restricted stock liability was reclassified into stockholders’ equity as the restricted stock vested. A summary of thestatus of unvested restricted stock as of December 31, 2018 and 2017, and changes during the year ended December 31, 2018 are presented below:F-27Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued) RestrictedStock Weighted-AverageGrant DateFair ValueUnvested at December 31, 20174,430 $11.43Vested(4,430) 11.43Unvested at December 31, 2018— The Company did not grant restricted stock to non-employees during the year ended December 31, 2018. Non-employee restricted stock is revalued as itvests. There were no shares of non-employee unvested restricted stock outstanding at December 31, 2018. The expense related to the restricted stock grantedto non-employees for the years ended December 31, 2018, 2017 and 2016 was $0, $0 and $3,000, respectively.Restricted Stock UnitsFrom time to time, upon approval by the Board, certain employees have been granted restricted stock units. However, the Company did not issue anyrestricted stock units to non-employees during the years ended December 31, 2018, 2017 and 2016.Performance-Based Stock OptionsThe Company has granted stock options to employees and founders of the Company, which contain both performance-based and service-based vestingcriteria. Milestone events are specific to the Company’s corporate goals, including but not limited to certain preclinical and clinical development milestonesrelated to the Company’s product candidates and financing objectives. Stock-based compensation expense associated with these performance-based stockoptions is recognized if the performance condition is considered probable of achievement using management’s best estimates. In the year endedDecember 31, 2016, the compensation committee of the Board determined that performance-based milestones were achieved and recorded stock-basedcompensation of $40,000. In October 2017, the Company granted 870,000 stock options with a fair value of $1.12 to executives that vest upon achievementof certain Company objectives. In the year ended December 31, 2017, the Company deemed it probable that two of the performance-based milestones wereachieved and recorded stock-based compensation of $344,000. In the year ended December 31, 2018, one performance-based milestone was achieved and theCompany deemed it probable that a second performance-based milestone will be achieved and recorded stock-based compensation of $240,000. As ofDecember 31, 2018, there were 229,005 performance-based stock options outstanding and $12,000 of unrecognized compensation expense remaining relatedto performance based-awards.Stock-Based Compensation ExpenseThe fair value of each stock option granted to employees and directors was estimated on the date of grant using the Black-Scholes option-pricing modelbased on the assumptions noted in the following table: Year Ended December 31, 2018 2017 2016Risk-free interest rate2.47-2.97% 1.88-2.04% 1.23-2.38%Expected dividend yield—% —% —%Expected term (in years)5.75-6 5.3-6 5.5-6Expected volatility73.61-78.28% 75.4-86.66% 71.44-73.42%VolatilitySince the Company has only been publicly traded since February 6, 2014, it does not have relevant historical data to support its expected volatility. As such,the Company has used a weighted-average of expected volatility based on the volatilities of a representative group of publicly traded biopharmaceuticalcompanies. For purposes of identifying representative companies, the Company considered characteristics such as stage of development and area oftherapeutic focus. The expected volatility has been determined using a weighted-average of the historical volatilities of the representative group ofcompanies for a period equal to the expected term of the option grant. The Company intends to continue to consistently apply this process using the similarentities until a sufficient amount of historical information regarding the volatility of the Company’s own share priceF-28Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)becomes available or until circumstances change, such that the identified entities are no longer representative companies. In the latter case, more suitable,similar entities whose share prices are publicly available would be utilized in the calculation.Risk-Free RateThe risk-free rate is based on the yield curve of U.S. Treasury securities with periods commensurate with the expected term of the options being valued.Expected TermThe Company uses the “simplified method” to estimate the expected term of stock option grants. Under this approach, the weighted-average expected life ispresumed to be the average of the contractual term (ten years) and the vesting term (generally four years) of the Company’s stock options, taking intoconsideration multiple vesting tranches. The Company utilizes this method due to lack of historical exercise data and the plain-vanilla nature of theCompany’s share-based awards.DividendsThe Company has never paid, and does not anticipate paying, any cash dividends in the foreseeable future, and therefore uses an expected dividend yield ofzero in the option-pricing model.ForfeituresPrior to January 1, 2017, the Company was required to estimate forfeitures at the time of grant, and revised those estimates in subsequent periods if actualforfeitures differed from its estimates. The Company used historical data to estimate pre-vesting option forfeitures and recorded stock-based compensationexpense only for those awards that were expected to vest. To the extent that actual forfeitures differed from the Company’s estimates, the difference wasrecorded as a cumulative adjustment in the period the estimates were revised. The Company now records forfeitures as they occur. Stock-based compensationexpense recognized in the consolidated financial statements is based on awards that ultimately vest.Using the Black-Scholes option-pricing model, the weighted-average per share grant date fair values of options granted to employees in 2018, 2017 and2016 were $1.14, $1.18, and $1.09, respectively. The expense related to the options granted to employees for the years ended December 31, 2018, 2017 and2016 were $1.0 million, $0.8 million, and $3.3 million, respectively.The Company granted 5,000 stock options to non-employees during the year ended December 31, 2016 with an exercise price of $0.28 per share. TheCompany did not grant stock options to non-employees during the years ended December 31, 2018 and 2017. There were no non-employee stock optionsoutstanding at December 31, 2018. There was no expense related to options granted to non-employees for the years ended December 31, 2018, 2017 and2016.As of December 31, 2018, there was $3.1 million of unrecognized stock-based compensation related to unvested stock option grants which is expected to berecognized over a weighted-average period of 3.2 years.Employee Stock Purchase PlanOn January 21, 2014, the Board adopted the 2014 Employee Stock Purchase Plan (“2014 ESPP”), which was subsequently approved by the Company'sstockholders and became effective upon the closing of the Company’s IPO on February 6, 2014. The 2014 ESPP authorizes the initial issuance of up to a totalof 157,480 shares of the Company’s common stock to participating employees. On March 14, 2016, the Company issued and sold 20,760 shares of itscommon stock at a purchase price of $0.31 per share and on September 14, 2016, issued and sold 68,111 shares of its common stock at a purchase price of$0.42 per share. On March 14, 2017, the Company issued and sold 2,899 shares of its common stock pursuant to the 2014 ESPP at a purchase price of $1.71per share. On September 14, 2017, the Company issued and sold 6,249 shares of its common stock pursuant to the 2014 ESPP at a purchase price of $1.19 pershare. On March 14, 2018, the Company issued and sold 9,565 shares of its common stock pursuant to the 2014 ESPP at a purchase price of $0.98 per share.On September 14, 2018, the Company issued and sold 11,427 shares of its common stock pursuant to the 2014 ESPP at a purchase price of $0.95 per share.The Company has estimated the number of shares to be issued at the end of the current offering period and recognizes expenseF-29Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)over the requisite service period. The Company recognized $8,000 and $12,000 of stock-based compensation related to the 2014 ESPP during the yearsended December 31, 2018 and 2017, respectively.Acceleration of Equity AwardsIn connection with the closing of the Acquisition, certain officers of the Company were terminated and entered into separation agreements with theCompany. Under the separation agreements, the Company accelerated in full the vesting of all of their outstanding equity awards consistent with theirexisting employment agreements. As a result of the acceleration, the Company recognized $1.7 million of stock-based compensation expense. In addition,the Company provided that all stock options granted to Dr. Celniker under the Company’s 2009 Plan shall continue to be exercisable based on her continuedservice as a non-employee member of the Board. As a result of this modification, the Company recorded $0.1 million of stock-based compensation expense inthe year ended December 31, 2017.13. Income TaxesThe Company's pre-tax income (loss) is comprised of the following components (in thousands): Year Ended December 31, 2018 2017 2016Pre-tax income (loss): U.S.(15,977) $(9,246) $3,981 Canada(17,716) (19,783) (2,085) Total pre-tax income (loss)$(33,693) $(29,029) $1,896The Company's tax provision is comprised of the following components (in thousands): Year Ended December 31, 2018 2017 2016Current tax provision: Federal$— $— $2 State— — — Foreign— — — Total current provision— — 2Deferred tax provision: Federal— — 3 State— — — Foreign— — — Total deferred provision — 3Total tax provision$— $— $5A reconciliation of the expected income tax expense computed using the federal statutory income tax rate to the Company’s effective income tax rate was asfollows:F-30Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued) Year Ended December 31, 2018 2017 2016Income tax benefit computed at federal statutory tax rate21.0 % 34.0 % 34.0 %Impact of foreign rate differential1.6 (2.6) 7.7State taxes, net of federal benefit1.3 1.4 18.8Net operating loss write off— — 14.4Stock option cancellations(1.2) (0.8) 49.6Transaction costs— — 33.6Contingent consideration(5.5) (10.7) (15.7)General business credits and other credits0.7 0.8 (25.0)Permanent differences(0.3) 0.3 5.3Change in valuation allowance(18.1) 28.2 (122.4)Other0.5 — —Federal statutory rate change— (50.6) —Total— % — % 0.3 %The Company has incurred net operating losses ("NOLs" or "NOL") from inception. At December 31, 2018, the Company has U.S. federal and state NOLcarryforwards of $134.7 million and $129.1 million, respectively, available to reduce future taxable income. $119.2 million of the U.S. federal NOLcarryforwards and $129.1 million of the state NOL carryforwards expire beginning 2030 through 2038. $15.5 million of the U.S. federal NOL carryforwardswill be carried forward indefinitely. The Company also had federal and state research and development tax credit carryforwards of $2.0 million and $0.9million, respectively, available to reduce future tax liabilities. The federal research and development tax credits expire beginning in 2029 through 2038. Thestate research and development tax credits expire beginning in 2027 through 2031. As of December 31, 2018, the Company also has non-capital losscarryforwards available to offset future taxable income of $25.0 million for Canadian federal tax purposes that expire beginning in 2035 through 2038. As ofDecember 31, 2018, the Company also has $5.3 million of Canadian scientific research and experimental development expense carryforwards available tooffset future taxable income as well as $1.2 million of Canadian federal and provincial investment tax credit carryforwards available to offset future incometaxes. The investment tax credits expire beginning in 2032 through 2038.Under Section 382 of the Internal Revenue Code of 1986 and comparable provisions of state, local and foreign tax laws, if a corporation undergoes an“ownership change,” generally defined as a greater than 50% change by value in its equity ownership over a three year period, the corporation’s ability to useits pre-change NOL carryforwards and other pre-change tax attributes, such as research and development tax credits, to reduce its post-change income may belimited. We have completed studies through March 31, 2016, to determine whether any ownership change has occurred since our formation and determinedthat it is more likely than not that our net operating and tax credit amounts disclosed are subject to a material limitation under Section 382 and as such, havereduce our NOL carryforward by $0.8 million. There could be additional ownership changes in the future that could further limit the amount of net operatingloss and tax credit carryforwards that we can utilize.The Company’s deferred tax assets and liabilities consist of the following (in thousands):F-31Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued) December 31, 2018 2017Deferred tax assets: Net operating loss carryforwards$43,212 $37,070Research and development credit carryforwards3,876 3,690Accruals and other2,011 2,263Capitalized start-up costs122 150Other32 38Total gross deferred tax asset49,253 43,211Deferred tax liabilities: IPR&D(12,528) (12,528)Property and equipment(60) (107)Total gross deferred tax liabilities(12,588) (12,635)Valuation allowance(49,193) (43,104)Net deferred tax liability$(12,528) $(12,528)As required by ASC 740, Income Taxes (“ASC 740”), management of the Company has evaluated the positive and negative evidence bearing upon therealizability of its deferred tax assets, which are composed principally of NOL carryforwards and research and development credit carryforwards. Managementhas determined that it is more likely than not that the Company will not recognize the benefits of its federal and state deferred tax assets, and, as a result, avaluation allowance of $49.2 million and $43.1 million has been established at December 31, 2018 and 2017, respectively. The change in the valuationallowance was for $6.1 million for the year ended December 31, 2018. The Company has not, as yet, conducted a study of its research and development creditcarryforwards. Such a study may result in an adjustment to the Company’s research and development credit carryforwards; however, until a study iscompleted and any adjustment is known, no amount is being presented as an uncertain tax position. A full valuation allowance has been provided against theCompany’s research and development credits, and, if an adjustment is required, this adjustment would be offset by an adjustment to the valuation allowance.Thus, there would be no impact to the consolidated balance sheets or consolidated statements of operations and comprehensive (loss) income if anadjustment were required.The Company applies the accounting guidance in ASC 740 related to accounting for uncertainty in income taxes. The Company’s reserves related to taxesare based on a determination of whether, and how much of, a tax benefit taken by the Company in its tax filings or positions is more likely than not to berealized following resolution of any potential contingencies present related to the tax benefit. As of December 31, 2018 and 2017, the Company had nounrecognized tax benefits. The Company recognizes interest and penalties related to uncertain tax positions in income tax expense.In December 2017, the SEC staff issued SAB 118 to address the application of GAAP in situations when a registrant does not have the necessary informationavailable, prepared, or analyzed (including computations) in reasonable detail to complete the accounting for certain income tax effects of the Tax ReformAct. The Company recognized the provisional tax impacts related to the revaluation of deferred tax assets and liabilities and included these amounts in itsconsolidated financial statements for the year ended December 31, 2017. The Company did not record any adjustments in the year ended December 31, 2018to these provisional amounts that were material to its financial statements. As of December 31, 2018, the Company’s accounting treatment is complete.The Company files income tax returns in the U.S., certain state and Canadian tax jurisdictions. Since the Company is in a loss carryforward position, theCompany is generally subject to examination by the U.S., certain state and Canadian income tax authorities for all tax years in which a loss carryforward isavailable. There are currently no audits in process in any of its tax filing jurisdictions.14. Related-Party TransactionThe Company leases a manufacturing, laboratory, and office facility in Winnipeg, Manitoba, from an affiliate of a director of the Company, under a five-yearrenewable lease through September 2020 with a right to renew the lease for one subsequent five-year term. Rent expense, which includes base rent and relatedoperating expenses, was $297,000 for the year endedF-32Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)December 31, 2018, $320,000 for the year ended December 31, 2017 and $86,000 for the period beginning on the Acquisition Date through December 31,2016.The Company leases an office facility in Toronto, Ontario from an affiliate of a director of the Company. The lease is on a month-to-month basis unlessterminated by either party by giving the requisite notice. Rent expense for this facility was $18,000 for the year ended December 31, 2018, $18,000 for theyear ended December 31, 2017 and $5,000 for the period beginning on the Acquisition Date through December 31, 2016.The Company pays fees, under an intellectual property license agreement, to Protoden, a company owned by Clairmark, an affiliate of a director of theCompany, under an intellectual property licensing agreement. Pursuant to the agreement, the Company has an exclusive, perpetual, irrevocable and non-royalty bearing license, with the right to sublicense, under certain patents and technology to make, use and sell products that utilize such patents andtechnology. The annual fee is $100,000. Upon expiration of the term, the licenses granted to the Company will require no further payments to Protoden.During the years ended December 31, 2018 and 2017, respectively, $100,000 was paid to this related party and for the period from the Acquisition Date toDecember 31, 2016, $28,000 was paid to this related party.In connection with the forgiveness of certain debt held by Viventia immediately preceding the Acquisition, the Company irrevocably assigned the right toreceive up to $814,000 in the form of research and development investment tax credits to and in favor of Clairmark, an affiliate of a director of the Company.In October 2016, the Company received $697,000 in research and development investment tax credits and in November 2016, the Company remitted thesame amount to Clairmark in full satisfaction of the obligation. As of December 31, 2018 and 2017, the Company did not have any amounts due to relatedparty on the accompanying consolidated balance sheets.15. Defined Contribution Benefit PlanThe Company sponsors a 401(k) retirement plan, in which substantially all of its full-time U.S. employees are eligible to participate. Participants maycontribute a percentage of their annual compensation to this plan, subject to statutory limitations. The Company made matching contributions of $18,000and $19,000 to this plan during the years ended December 31, 2018 and 2017, respectively. The Company did not provide any contributions to this planduring the year ended December 31, 2016. Through 2016, Viventia sponsored a 401(k) retirement plan for its U.S.-based employees. Participants contributeda percentage of their annual compensation to this plan, subject to statutory limitations. The Company made matching contributions of $8,000 for the periodfrom the Acquisition Date through December 31, 2016 to this plan. Viventia did not have any U.S.-based employees in 2017 or 2018.The Company maintains a defined contribution plan for its Canadian employees. Participants may contribute a percentage of their annual compensation tothis plan, subject to statutory limitations. The Company contributes up to the first 4% of eligible compensation for its Canadian-based employees to theretirement plan. The Company made contributions of $45,000 and $64,000 for the years ended December 31, 2018 and 2017, respectively, and $14,000 forthe period from the Acquisition Date through December 31, 2016 to this plan.16. Reductions in WorkforceOn June 16, 2016, the Board approved a strategic restructuring of the Company to eliminate a portion of the Company’s workforce in order to preserve theCompany’s resources as it determined its future strategic plans. The Company estimated total restructuring costs of $0.6 million in connection with thisaction, which included severance, benefits and related costs in accordance with the Company's severance benefit plan. On September 20, 2016, in connectionwith the Acquisition, the Company eliminated additional positions and recorded additional restructuring charges of $1.3 million. The Company recordedrestructuring charges of $1.1 million in research and development expenses and $0.8 million in general and administrative expenses in the consolidatedstatements of operations and comprehensive income (loss) for the year ended December 31, 2016.On August 15, 2017, the Board approved a strategic restructuring of the Company to eliminate a portion of the Company’s workforce in order to preserve theCompany’s resources. On September 22, 2017, the Company announced that it has completed the manufacturing of all Vicinium necessary for its ongoingPhase 3 registration trial in patients with NMIBC, and for its Cooperative Research and Development Agreement with the National Cancer Institute. Inconjunction with thisF-33Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)achievement, the Company ended its large-scale manufacturing activities and redirected resources toward completing its Phase 3 trial and preparing fordiscussions with the U.S. Food and Drug Administration regarding, as appropriate, the submission of a Biologics License Application for Vicinium inpatients with NMIBC. As of December 31, 2017, the Company estimated total restructuring costs of approximately $0.1 million, which included severanceand benefits in accordance with the Company's severance benefit plan, all of which was recorded in the third quarter of 2017.The table below provides a roll-forward of the reduction in workforce liability (in thousands): Balance as of January 1, 2018$111 Charges— Payments(111) Balance as of December 31, 2018$—17. Cash, Cash Equivalents and Restricted Cash The following table provides a reconciliation of cash, cash equivalents and restricted cash reported within the consolidated balance sheets that sum to thetotal of the same such amounts shown in the consolidated statements of cash flows (in thousands): As of December 31, 20182017Cash and Cash Equivalents$50,422$14,680Restricted Cash2010Total Cash, Cash Equivalents and Restricted Cash$50,442$14,690Amounts included in restricted cash represent cash held to collateralize a credit limit with Silicon Valley Bank of $20,000 and $10,000 as of December 31,2018 and December 31, 2017, respectively.18. Subsequent EventNasdaq Listing Non-compliance NoticeOn February 19, 2019, the Company received written notice (the “Notice”) from The Nasdaq Stock Market, LLC (“Nasdaq”) indicating that the Company isnot in compliance with the $1.00 minimum bid price requirement for continued listing on The Nasdaq Global Market, as set forth in Nasdaq Listing Rule5450(a)(1). The Notice has no effect at this time on the listing of the Company’s common stock (the “Common Stock”), which will continue to trade on TheNasdaq Global Market under the symbol “SESN”.In accordance with Nasdaq Listing Rule 5810(c)(3)(A), the Company has a period of 180 calendar days, or until August 19, 2019, to regain compliance withthe minimum bid price requirement. To regain compliance, the closing bid price of the Company’s Common Stock must meet or exceed $1.00 per share for aminimum of ten consecutive business days during this 180-day period. If the Company is not in compliance by August 19, 2019, the Company may beafforded a second 180 calendar day period to regain compliance. To qualify, the Company would be required to apply to have its Common Stock listed onthe Nasdaq Capital Market and meet the continued listing requirement for market value of publicly held shares and all other initial listing standards for TheNasdaq Capital Market, except for the minimum bid price requirement, and will need to provide written notice to Nasdaq of its intention to cure thedeficiency during the second compliance period, by effecting a reverse stock split, if necessary.The Company intends to monitor the closing bid price of its Common Stock and may, if appropriate, consider implementing available options to regaincompliance with the minimum bid price requirement under the Nasdaq Listing Rules.F-34Table of ContentsSESEN BIO, INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (continued)February 2019 Stock Option GrantsOn February 21, 2019, the Company’s Board of Directors issued 1,720,375 stock option grants from the Company’s 2014 Plan to certain executive officersand employees of the Company. These stock options had an exercise price of $0.8285 per share, which was the closing stock price for the Company’sCommon Stock on February 21, 2019. On February 27, 2019, the Company's Board of Directors issued 260,000 stock option grants from the Company's 2014Plan to a non-employee consultant of the Company. These stock options had an exercise price of $1.0000 per share, which was the closing stock price for theCompany’s Common Stock on February 27, 2019.19. Selected Quarterly Financial Data (Unaudited)The following table contains quarterly financial information for 2018 and 2017. The Company believes that the following information reflects all normalrecurring adjustments necessary for a fair statement of the information for the periods presented. The operating results for any quarter are not necessarilyindicative of results for any future period. 2018 FirstQuarter SecondQuarter ThirdQuarter FourthQuarter Total (in thousands, except per share data)Total revenue$— $— $— $— $—Total operating expenses4,007 9,030 14,397 $7,066 34,500Loss from operations(4,007) (9,030) (14,397) $(7,066) (34,500)Net loss(3,963) (8,958) (14,015) $(6,757) $(33,693)Net loss per share—basic and diluted$(0.11) $(0.16) $(0.18) $(0.09) $(0.55) 2017 FirstQuarter SecondQuarter ThirdQuarter FourthQuarter Total (in thousands, except per share data)Total revenue$425 $— $— $— $425Total operating expenses6,587 7,350 9,150 $6,593 29,680Loss from operations(6,162) (7,350) (9,150) $(6,593) (29,255)Net loss(6,061) (7,316) (9,105) $(6,547) $(29,029)Net loss per share—basic and diluted$(0.25) $(0.30) $(0.37) $(0.22) $(1.11)F-35Sesen Bio, Inc.Nonstatutory Stock Option Agreement1.Grant of Option.This agreement evidences the grant by Sesen Bio, Inc., a Delaware corporation (the “Company”), on August 7, 2018 (the“Grant Date”) to Thomas R. Cannell, D.V.M. (the “Participant”), of an option to purchase, in whole or in part, on the terms providedherein, a total of 1,350,000 shares (the “Shares”) of common stock, $0.001 par value per share, of the Company (“Common Stock”) at$1.60 per Share. Unless earlier terminated, this option shall expire at 5:00 p.m., Eastern time, on August 7, 2028 (the “Final ExerciseDate”).The option evidenced by this agreement was granted to the Participant pursuant to the inducement grant exception underNasdaq Stock Market Rule 5635(c)(4), and not pursuant to the Company’s 2014 Stock Incentive Plan (the “Plan”) or any equityincentive plan of the Company, as an inducement that is material to the Participant’s employment with the Company.It is intended that the option evidenced by this agreement shall not be an incentive stock option as defined in Section 422 of theInternal Revenue Code of 1986, as amended, and any regulations promulgated thereunder (the “Code”). Except as otherwise indicatedby the context, the term “Participant”, as used in this option, shall be deemed to include any person who acquires the right to exercisethis option validly under its terms.2.Vesting Schedule.Except as otherwise provided herein, this option will become exercisable (“vest”) as to 25% of the original number of Shareson one-year anniversary of the Grant Date and as to an additional 6.25% of the original number of Shares at the end of each successivethree-month period following the one-year anniversary of the Grant Date until the fourth anniversary of the Grant Date.The right of exercise shall be cumulative so that to the extent the option is not exercised in any period to the maximum extentpermissible it shall continue to be exercisable, in whole or in part, with respect to all Shares for which it is vested until the earlier of theFinal Exercise Date or the termination of this option under Section 3 hereof.3.Exercise of Option.(a)Form of Exercise. Each election to exercise this option shall be in writing, signed by the Participant (or such electronicnotice as is approved by the Company), and received by the Company at its principal office, accompanied by this agreement andpayment in full as follows:(1)in cash or by check, payable to the order of the Company;(2) by (i) delivery of an irrevocable and unconditional undertaking by a creditworthy broker to deliver promptly to theCompany sufficient funds to pay the exercise price and any required tax withholding or (ii) delivery by the Participant to the Companyof a copy of irrevocable and unconditional instructions to a creditworthy broker to deliver promptly to the Company cash or a checksufficient to pay the exercise price and any required tax withholding;(3) to the extent approved by the Board of Directors of the Company (the “Board”), in its sole discretion, by delivery(either by actual delivery or attestation) of shares of Common Stock owned by the Participant valued at their fair market value per shareas determined by (or in a manner approved by) the Board (the “Fair Market Value”), provided (i) such method of payment is thenpermitted under applicable law, (ii) such Common Stock, if acquired directly from the Company, was owned by the Participant forsuch minimum period of time, if any, as may be established by the Board in its discretion and (iii) such Common Stock is not subject toany repurchase, forfeiture, unfulfilled vesting or other similar requirements;(4) to the extent approved by the Board, in its sole discretion, by delivery of a notice of “net exercise” to the Company, asa result of which the Participant would receive (i) the number of shares underlying the portion of this being exercised, less (ii) suchnumber of shares as is equal to (A) the aggregate exercise price for the portion of this option being exercised divided by (B) the FairMarket Value on the date of exercise;(5) to the extent permitted by applicable law or approved by the Board, in its sole discretion, by payment of such otherlawful consideration as the Board may determine; or(6) by any combination of the above permitted forms of payment.The Participant may purchase less than the number of shares covered hereby, provided that no partial exercise of this option may be forany fractional share or for fewer than ten whole shares.(b) Continuous Relationship with the Company Required. Except as otherwise provided in this Section 3, this option may notbe exercised unless the Participant, at the time he exercises this option, is, and has been at all times since the Grant Date, an employee,officer or a director of, or consultant or advisor to, the Company or any other entity the employees, officers, directors, consultants, oradvisors of which are eligible to receive option grants under the Plan (an “Eligible Participant”).(c) Termination of Relationship with the Company. If the Participant ceases to be an Eligible Participant for any reason, then,except as provided in paragraphs (d) and (e) below, the right to exercise this option shall terminate three months after such cessation(but in no event after the Final Exercise Date), provided that this option shall be exercisable only to the extent that the Participant wasentitled to exercise this option on the date of such cessation. Notwithstanding the foregoing, if the Participant, prior to the Final Exercise Date, violates the non-competition or confidentialityprovisions of any employment contract, confidentiality and nondisclosure agreement or other agreement between the Participant andthe Company, the right to exercise this option shall terminate immediately upon written notice to the Participant from the Companydescribing such violation.(d) Exercise Period Upon Death or Disability. If the Participant dies or becomes disabled (within the meaning ofSection 22(e)(3) of the Code) prior to the Final Exercise Date while he is an Eligible Participant and the Company has not terminatedsuch relationship for “cause” as specified in paragraph (e) below, this option shall be exercisable, within the period of one yearfollowing the date of death or disability of the Participant, by the Participant (or in the case of death by an authorized transferee),provided that this option shall be exercisable only to the extent that this option was exercisable by the Participant on the date of hisdeath or disability, and further provided that this option shall not be exercisable after the Final Exercise Date.(e) Termination for Cause. If the Participant, prior to the Final Exercise Date, is terminated by the Company for Cause (asdefined in the letter agreement, dated as of August 7, 2018 between the Participant and the Company, or any successor agreementthereto (the “Letter Agreement”)), the right to exercise this option shall terminate immediately upon the effective date of suchtermination.(f) Letter Agreement. Notwithstanding anything to the contrary in this Section 3 or in Section 7, this option shall be subject toany applicable vesting terms set forth in the Letter Agreement, including the accelerated vesting provisions set forth in the LetterAgreement applicable in connection with certain terminations within the specified period following a Change in Control Transaction(as defined in the Letter Agreement). 4.Agreement in Connection with Public Offering.The Participant agrees, in connection with an underwritten public offering of the Common Stock pursuant to a registrationstatement under the Securities Act, (i) not to (a) offer, pledge, announce the intention to sell, sell, contract to sell, sell any option orcontract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, or otherwise transfer ordispose of, directly or indirectly, any shares of Common Stock or any other securities of the Company or (b) enter into any swap orother agreement that transfers, in whole or in part, any of the economic consequences of ownership of shares of Common Stock orother securities of the Company, whether any transaction described in clause (a) or (b) is to be settled by delivery of securities, in cashor otherwise, during the period beginning on the date of the filing of such registration statement with the Securities and ExchangeCommission and ending 90 days after the date of the final prospectus relating to the offering (plus up to an additional 34 days to theextent requested by the managing underwriters for such offering in order to address Rule 2711(f) of the Financial Industry RegulatoryAuthority or any similar successor provision), and (ii) to execute any agreement reflecting clause (i) above as may be requested by theCompany or the managing underwriters at the time of such offering. The Company may impose stop-transfer instructions with respectto the shares of Common Stock or other securities subject to the foregoing restriction until the end of the “lock-up” period.5.Withholding.No Shares will be issued pursuant to the exercise of this option unless and until the Participant pays to the Company, or makesprovision satisfactory to the Company for payment of, any federal, state or local withholding taxes required by law to be withheld inrespect of this option. The Participant must satisfy all applicable federal, state, and local or other income and employment taxwithholding obligations before the Company will deliver stock certificates or otherwise recognize ownership of Common Stock underthis option. The Company may decide to satisfy the withholding obligations through additional withholding on salary or wages. If theCompany elects not to or cannot withhold from other compensation, the Participant must pay the Company the full amount, if any,required for withholding or have a broker tender to the Company cash equal to the withholding obligations. Payment of withholdingobligations is due before the Company will issue any shares on exercise of this option or at the same time as payment of the exerciseprice, unless the Company determines otherwise. If approved by the Board, in its sole discretion, a Participant may satisfy such taxobligations in whole or in part by delivery (either by actual delivery or attestation) of shares of Common Stock underlying this optionvalued at their Fair Market Value; provided, however, except as otherwise provided by the Board, that the total tax withholding wherestock is being used to satisfy such tax obligations cannot exceed the Company’s minimum statutory withholding obligations (based onminimum statutory withholding rates for federal and state tax purposes, including payroll taxes, that are applicable to suchsupplemental taxable income), except that, to the extent that the Company is able to retain shares of Common Stock having a fairmarket value (determined by (or in a manner approved by) the Company) that exceeds the statutory minimum applicable withholdingtax without financial accounting implications or the Company is withholding in a jurisdiction that does not have a statutory minimumwithholding tax, the Company may retain such number of shares of Common Stock (up to the number of shares having a fair marketvalue equal to the maximum individual statutory rate of tax (determined by (or in a manner approved by) the Company)) as theCompany shall determine in its sole discretion to satisfy the tax liability associated with any Award. Shares used to satisfy taxwithholding requirements cannot be subject to any forfeiture, unfulfilled vesting or other similar requirements.6.Transfer Restrictions.This option may not be sold, assigned, transferred, pledged or otherwise encumbered by the Participant, either voluntarily or byoperation of law, except by will or the laws of descent and distribution, and, during the lifetime of the Participant, this option shall beexercisable only by the Participant.7.Adjustments for Changes in Common Stock and Certain Other Events.(a)Changes in Capitalization. In the event of any stock split, reverse stock split, stock dividend, recapitalization,combination of shares, reclassification of shares, spin-off or other similar change in capitalization or event, or anydividend or distribution to holders of Common Stock other than an ordinary cash dividend, the number and class ofsecurities and exercise price per share of this option shall be equitably adjusted by the Company in the mannerdetermined by the Board. Without limiting the generality of the foregoing, in the event the Company effects a split ofthe Common Stock by means of a stock dividend and the exercise price of and the number of shares subject to thisoption are adjusted as of the date of the distribution of the dividend (rather than as of the record date for such dividend),then the Participant, if he exercises this option between the record date and the distribution date for such stock dividend,shall be entitled to receive, on the distribution date, the stock dividend with respect to the shares of Common Stockacquired upon exercise of this option, notwithstanding the fact that such shares were not outstanding as of the close ofbusiness on the record date for such stock dividend.(b) Reorganization Events. A “Reorganization Event” shall mean: (a) any merger or consolidation of the Company with orinto another entity as a result of which all of the Common Stock of the Company is converted into or exchanged for the right to receivecash, securities or other property or is cancelled, (b) any transfer or disposition of all of the Common Stock of the Company for cash,securities or other property pursuant to a share exchange or other transaction or (c) any liquidation or dissolution of the Company. Inconnection with a Reorganization Event, the Board may take any one or more of the following actions with respect to this option (orany portion thereof) on such terms as the Board determines: (i) provide that this option shall be assumed, or substantially equivalentoption shall be substituted, by the acquiring or succeeding corporation (or an affiliate thereof), (ii) upon written notice to theParticipant, provide that the unvested and/ or unexercised portion of this option will terminate immediately prior to the consummationof such Reorganization Event unless exercised by the Participant within a specified period following the date of such notice,(iii) provide that this option shall become exercisable, realizable, or deliverable, or restrictions applicable to this option shall lapse, inwhole or in part prior to or upon such Reorganization Event, (iv) in the event of a Reorganization Event under the terms of whichholders of Common Stock will receive upon consummation thereof a cash payment for each share surrendered in the ReorganizationEvent (the “Acquisition Price”), make or provide for a cash payment to the Participant with respect to this option equal to (A) thenumber of shares of Common Stock subject to the vested portion of this option (after giving effect to any acceleration of vesting thatoccurs upon or immediately prior to such Reorganization Event) multiplied by (B) the excess, if any, of (I) the Acquisition Price over(II) the exercise price of this option and any applicable tax withholdings, in exchange for the termination of this option, (v) providethat, in connection with a liquidation or dissolution of the Company, this option shall convert into the right to receive liquidationproceeds (if applicable, net of the exercise, measurement or purchase price thereof and any applicable tax withholdings) and (vi) anycombination of the foregoing.For purposes of clause (i) above, this option shall be considered assumed if, following consummation of the ReorganizationEvent, this option confers the right to purchase, for each share of Common Stock subject to this option immediately prior to theconsummation of the Reorganization Event, the consideration (whether cash, securities or other property) received as a result of theReorganization Event by holders of Common Stock for each share of CommonStock held immediately prior to the consummation of the Reorganization Event (and if holders were offered a choice ofconsideration, the type of consideration chosen by the holders of a majority of the outstanding shares of Common Stock); provided,however, that if the consideration received as a result of the Reorganization Event is not solely common stock of the acquiring orsucceeding corporation (or an affiliate thereof), the Company may, with the consent of the acquiring or succeeding corporation,provide for the consideration to be received upon the exercise of this option to consist solely of such number of shares of commonstock of the acquiring or succeeding corporation (or an affiliate thereof) that the Board determined to be equivalent in value (as of thedate of such determination or another date specified by the Board) to the per share consideration received by holders of outstandingshares of Common Stock as a result of the Reorganization Event.8.Miscellaneous.(a)No Right To Employment or Other Status. The grant of this option shall not be construed as giving the Participant theright to continued employment or any other relationship with the Company. The Company expressly reserves the rightat any time to dismiss or otherwise terminate its relationship with the Participant free from any liability or claimhereunder, except as otherwise expressly provided herein or provided for in the Letter Agreement.(b) No Rights As Stockholder. Subject to the provisions of this option, the Participant shall not have any rights as astockholder with respect to any shares of Common Stock to be distributed with respect to this option until becoming the record holderof such shares.(c) Entire Agreement. This Agreement, together with the Letter Agreement, constitute the entire agreement between theparties, and supersede all prior agreements and understandings, relating to the subject matter hereof.(d) Amendment. Except with respect to any vesting terms set forth in the Letter Agreement, the Board may amend, modify orterminate this Agreement, including but not limited to, substituting another option of the same or a different type and changing the dateof exercise or realization. Notwithstanding the foregoing, the Participant’s consent to such action shall be required unless (i) the Boarddetermines that the action, taking into account any related action, would not materially and adversely affect the Participant, or (ii) thechange is permitted under Section 7 and the Letter Agreement.(e) Acceleration. The Board may at any time provide that this option shall become immediately exercisable in whole or inpart, free of some or all restrictions or conditions, or otherwise realizable in whole or in part, as the case may be.(f) Conditions on Delivery of Stock. The Company will not be obligated to deliver any shares of Common Stock pursuant tothis Agreement until (i) all conditions of this Agreement have been met to the satisfaction of the Company, (ii) in the opinion of theCompany’s counsel, all other legal matters in connection with the issuance and delivery of such shares have been satisfied, includingany applicable securities laws and regulations and any applicable stock exchange or stock market rules and regulations, and (iii) theParticipant has executed and delivered to the Company such representations or agreements as the Company may consider appropriateto satisfy the requirements of any applicable laws, rules or regulations.(g) Administration by Board. The Board will administer this Agreement and may construe and interpret the terms hereof. Subject to the terms and provisions of the Letter Agreement, the Board may correct any defect, supply any omission or reconcile anyinconsistency in this Agreement in the manner and to the extent it shall deem expedient to carry the Agreement into effect and it shallbe the sole and final judge of such expediency. No director or person acting pursuant to the authority delegated by the Board shall beliable for any action or determination relating to or under this Agreement made in good faith.(h) Appointment of Committees. To the extent permitted by applicable law, the Board may delegate any or all of its powershereunder to one or more committees or subcommittees of the Board (a “Committee”). All references herein to the “Board” shall meanthe Board or a Committee to the extent that the Board’s powers or authority hereunder have been delegated to such Committee.(i) Severability. The invalidity or unenforceability of any provision hereof shall not affect the validity or enforceability of anyother provision hereof, and each such other provision shall be severable and enforceable to the extent permitted by law.(j) Governing Law. This Agreement shall be governed by and interpreted in accordance with the laws of the State ofDelaware, excluding choice-of-law principles of the law of such state that would require the application of the laws of a jurisdictionother than the State of Delaware.(k) Counterparts. This Agreement may be executed in one or more counterparts, each of which shall be deemed to be anoriginal but all of which together will constitute one in the same instrument.[Remainder of Page Intentionally Blank]The Company has caused this option to be executed by its duly authorized officer. SESEN BIO, INC. By: /s/ Wendy L. Dixon Name: Wendy L. Dixon, Ph.D. Title: Chair of the Board of DirectorsThe undersigned hereby accepts the foregoing option and agrees to the terms and conditions thereof.PARTICIPANT /s/ Thomas R. Cannell Thomas R. Cannell, D.V.M.Address: 7722 Roseland DriveLa Jolla, California 92037 - 1 - Sesen Bio, Inc.Nonstatutory Stock Option Agreement1.Grant of Option.This agreement evidences the grant by Sesen Bio, Inc., a Delaware corporation (the “Company”), on December 3, 2018 (the“Grant Date”) to Dennis Kim, M.D., MPH (the “Participant”), of an option to purchase, in whole or in part, on the terms providedherein, a total of 425,000 shares (the “Shares”) of common stock, $0.001 par value per share, of the Company (“Common Stock”) at$1.70 per Share. Unless earlier terminated, this option shall expire at 5:00 p.m., Eastern time, on December 3, 2028 (the “FinalExercise Date”).The option evidenced by this agreement was granted to the Participant pursuant to the inducement grant exception underNasdaq Stock Market Rule 5635(c)(4), and not pursuant to the Company’s 2014 Stock Incentive Plan (the “Plan”) or any equityincentive plan of the Company, as an inducement that is material to the Participant’s employment with the Company.It is intended that the option evidenced by this agreement shall not be an incentive stock option as defined in Section 422 of theInternal Revenue Code of 1986, as amended, and any regulations promulgated thereunder (the “Code”). Except as otherwise indicatedby the context, the term “Participant”, as used in this option, shall be deemed to include any person who acquires the right to exercisethis option validly under its terms.2.Vesting Schedule.Except as otherwise provided herein, this option will become exercisable (“vest”) as to 25% of the original number of Shareson one-year anniversary of the Grant Date and as to an additional 6.25% of the original number of Shares at the end of each successivethree-month period following the one-year anniversary of the Grant Date until the fourth anniversary of the Grant Date.The right of exercise shall be cumulative so that to the extent the option is not exercised in any period to the maximum extentpermissible it shall continue to be exercisable, in whole or in part, with respect to all Shares for which it is vested until the earlier of theFinal Exercise Date or the termination of this option under Section 3 hereof.3.Exercise of Option.(a)Form of Exercise. Each election to exercise this option shall be in writing, signed by the Participant (or such electronicnotice as is approved by the Company), and received by the Company at its principal office, accompanied by this agreement andpayment in full as follows:(1)in cash or by check, payable to the order of the Company;(2) by (i) delivery of an irrevocable and unconditional undertaking by a creditworthy broker to deliver promptly to theCompany sufficient funds to pay the exercise price and any required tax withholding or (ii) delivery by the Participant to the Companyof a copy of irrevocable and unconditional instructions to a creditworthy broker to deliver promptly to the Company cash or a checksufficient to pay the exercise price and any required tax withholding;(3) to the extent approved by the Board of Directors of the Company (the “Board”), in its sole discretion, by delivery(either by actual delivery or attestation) of shares of Common Stock owned by the Participant valued at their fair market value per shareas determined by (or in a manner approved by) the Board (the “Fair Market Value”), provided (i) such method of payment is thenpermitted under applicable law, (ii) such Common Stock, if acquired directly from the Company, was owned by the Participant forsuch minimum period of time, if any, as may be established by the Board in its discretion and (iii) such Common Stock is not subject toany repurchase, forfeiture, unfulfilled vesting or other similar requirements;(4) to the extent approved by the Board, in its sole discretion, by delivery of a notice of “net exercise” to the Company, asa result of which the Participant would receive (i) the number of shares underlying the portion of this being exercised, less (ii) suchnumber of shares as is equal to (A) the aggregate exercise price for the portion of this option being exercised divided by (B) the FairMarket Value on the date of exercise;(5) to the extent permitted by applicable law or approved by the Board, in its sole discretion, by payment of such otherlawful consideration as the Board may determine; or(6) by any combination of the above permitted forms of payment.The Participant may purchase less than the number of shares covered hereby, provided that no partial exercise of this option may be forany fractional share or for fewer than ten whole shares.(b) Continuous Relationship with the Company Required. Except as otherwise provided in this Section 3, this option may notbe exercised unless the Participant, at the time he exercises this option, is, and has been at all times since the Grant Date, an employee,officer or a director of, or consultant or advisor to, the Company or any other entity the employees, officers, directors, consultants, oradvisors of which are eligible to receive option grants under the Plan (an “Eligible Participant”).(c) Termination of Relationship with the Company. If the Participant ceases to be an Eligible Participant for any reason, then,except as provided in paragraphs (d) and (e) below, the right to exercise this option shall terminate three months after such cessation(but in no event after the Final Exercise Date), provided that this option shall be exercisable only to the extent that the Participant wasentitled to exercise this option on the date of such cessation. Notwithstanding the foregoing, if the Participant, prior to the Final Exercise Date, violates the non-competition or confidentialityprovisions of any employment contract, confidentiality and nondisclosure agreement or other agreement between the Participant andthe Company, the right to exercise this option shall terminate immediately upon written notice to the Participant from the Companydescribing such violation.(d) Exercise Period Upon Death or Disability. If the Participant dies or becomes disabled (within the meaning ofSection 22(e)(3) of the Code) prior to the Final Exercise Date while he is an Eligible Participant and the Company has not terminatedsuch relationship for “cause” as specified in paragraph (e) below, this option shall be exercisable, within the period of one yearfollowing the date of death or disability of the Participant, by the Participant (or in the case of death by an authorized transferee),provided that this option shall be exercisable only to the extent that this option was exercisable by the Participant on the date of hisdeath or disability, and further provided that this option shall not be exercisable after the Final Exercise Date.(e) Termination for Cause. If the Participant, prior to the Final Exercise Date, is terminated by the Company for Cause (asdefined in the letter agreement, dated as of December 3, 2018 between the Participant and the Company, or any successor agreementthereto (the “Letter Agreement”)), the right to exercise this option shall terminate immediately upon the effective date of suchtermination.(f) Letter Agreement. Notwithstanding anything to the contrary in this Section 3 or in Section 7, this option shall be subject toany applicable vesting terms set forth in the Letter Agreement, including the accelerated vesting provisions set forth in the LetterAgreement applicable in connection with certain terminations within the specified period following a Change in Control Transaction(as defined in the Letter Agreement). 4.Agreement in Connection with Public Offering.The Participant agrees, in connection with an underwritten public offering of the Common Stock pursuant to a registrationstatement under the Securities Act, (i) not to (a) offer, pledge, announce the intention to sell, sell, contract to sell, sell any option orcontract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, or otherwise transfer ordispose of, directly or indirectly, any shares of Common Stock or any other securities of the Company or (b) enter into any swap orother agreement that transfers, in whole or in part, any of the economic consequences of ownership of shares of Common Stock orother securities of the Company, whether any transaction described in clause (a) or (b) is to be settled by delivery of securities, in cashor otherwise, during the period beginning on the date of the filing of such registration statement with the Securities and ExchangeCommission and ending 90 days after the date of the final prospectus relating to the offering (plus up to an additional 34 days to theextent requested by the managing underwriters for such offering in order to address Rule 2711(f) of the Financial Industry RegulatoryAuthority or any similar successor provision), and (ii) to execute any agreement reflecting clause (i) above as may be requested by theCompany or the managing underwriters at the time of such offering. The Company may impose stop-transfer instructions with respectto the shares of Common Stock or other securities subject to the foregoing restriction until the end of the “lock-up” period.5.Withholding.No Shares will be issued pursuant to the exercise of this option unless and until the Participant pays to the Company, or makesprovision satisfactory to the Company for payment of, any federal, state or local withholding taxes required by law to be withheld inrespect of this option. The Participant must satisfy all applicable federal, state, and local or other income and employment taxwithholding obligations before the Company will deliver stock certificates or otherwise recognize ownership of Common Stock underthis option. The Company may decide to satisfy the withholding obligations through additional withholding on salary or wages. If theCompany elects not to or cannot withhold from other compensation, the Participant must pay the Company the full amount, if any,required for withholding or have a broker tender to the Company cash equal to the withholding obligations. Payment of withholdingobligations is due before the Company will issue any shares on exercise of this option or at the same time as payment of the exerciseprice, unless the Company determines otherwise. If approved by the Board, in its sole discretion, a Participant may satisfy such taxobligations in whole or in part by delivery (either by actual delivery or attestation) of shares of Common Stock underlying this optionvalued at their Fair Market Value; provided, however, except as otherwise provided by the Board, that the total tax withholding wherestock is being used to satisfy such tax obligations cannot exceed the Company’s minimum statutory withholding obligations (based onminimum statutory withholding rates for federal and state tax purposes, including payroll taxes, that are applicable to suchsupplemental taxable income), except that, to the extent that the Company is able to retain shares of Common Stock having a fairmarket value (determined by (or in a manner approved by) the Company) that exceeds the statutory minimum applicable withholdingtax without financial accounting implications or the Company is withholding in a jurisdiction that does not have a statutory minimumwithholding tax, the Company may retain such number of shares of Common Stock (up to the number of shares having a fair marketvalue equal to the maximum individual statutory rate of tax (determined by (or in a manner approved by) the Company)) as theCompany shall determine in its sole discretion to satisfy the tax liability associated with any Award. Shares used to satisfy taxwithholding requirements cannot be subject to any forfeiture, unfulfilled vesting or other similar requirements.6.Transfer Restrictions.This option may not be sold, assigned, transferred, pledged or otherwise encumbered by the Participant, either voluntarily or byoperation of law, except by will or the laws of descent and distribution, and, during the lifetime of the Participant, this option shall beexercisable only by the Participant.7.Adjustments for Changes in Common Stock and Certain Other Events.(a)Changes in Capitalization. In the event of any stock split, reverse stock split, stock dividend, recapitalization,combination of shares, reclassification of shares, spin-off or other similar change in capitalization or event, or anydividend or distribution to holders of Common Stock other than an ordinary cash dividend, the number and class ofsecurities and exercise price per share of this option shall be equitably adjusted by the Company in the mannerdetermined by the Board. Without limiting the generality of the foregoing, in the event the Company effects a split ofthe Common Stock by means of a stock dividend and the exercise price of and the number of shares subject to thisoption are adjusted as of the date of the distribution of the dividend (rather than as of the record date for such dividend),then the Participant, if he exercises this option between the record date and the distribution date for such stock dividend,shall be entitled to receive, on the distribution date, the stock dividend with respect to the shares of Common Stockacquired upon exercise of this option, notwithstanding the fact that such shares were not outstanding as of the close ofbusiness on the record date for such stock dividend.(b) Reorganization Events. A “Reorganization Event” shall mean: (a) any merger or consolidation of the Company with orinto another entity as a result of which all of the Common Stock of the Company is converted into or exchanged for the right to receivecash, securities or other property or is cancelled, (b) any transfer or disposition of all of the Common Stock of the Company for cash,securities or other property pursuant to a share exchange or other transaction or (c) any liquidation or dissolution of the Company. Inconnection with a Reorganization Event, the Board may take any one or more of the following actions with respect to this option (orany portion thereof) on such terms as the Board determines: (i) provide that this option shall be assumed, or substantially equivalentoption shall be substituted, by the acquiring or succeeding corporation (or an affiliate thereof), (ii) upon written notice to theParticipant, provide that the unvested and/ or unexercised portion of this option will terminate immediately prior to the consummationof such Reorganization Event unless exercised by the Participant within a specified period following the date of such notice,(iii) provide that this option shall become exercisable, realizable, or deliverable, or restrictions applicable to this option shall lapse, inwhole or in part prior to or upon such Reorganization Event, (iv) in the event of a Reorganization Event under the terms of whichholders of Common Stock will receive upon consummation thereof a cash payment for each share surrendered in the ReorganizationEvent (the “Acquisition Price”), make or provide for a cash payment to the Participant with respect to this option equal to (A) thenumber of shares of Common Stock subject to the vested portion of this option (after giving effect to any acceleration of vesting thatoccurs upon or immediately prior to such Reorganization Event) multiplied by (B) the excess, if any, of (I) the Acquisition Price over(II) the exercise price of this option and any applicable tax withholdings, in exchange for the termination of this option, (v) providethat, in connection with a liquidation or dissolution of the Company, this option shall convert into the right to receive liquidationproceeds (if applicable, net of the exercise, measurement or purchase price thereof and any applicable tax withholdings) and (vi) anycombination of the foregoing.For purposes of clause (i) above, this option shall be considered assumed if, following consummation of the ReorganizationEvent, this option confers the right to purchase, for each share of Common Stock subject to this option immediately prior to theconsummation of the Reorganization Event, the consideration (whether cash, securities or other property) received as a result of theReorganization Event by holders of Common Stock for each share of CommonStock held immediately prior to the consummation of the Reorganization Event (and if holders were offered a choice ofconsideration, the type of consideration chosen by the holders of a majority of the outstanding shares of Common Stock); provided,however, that if the consideration received as a result of the Reorganization Event is not solely common stock of the acquiring orsucceeding corporation (or an affiliate thereof), the Company may, with the consent of the acquiring or succeeding corporation,provide for the consideration to be received upon the exercise of this option to consist solely of such number of shares of commonstock of the acquiring or succeeding corporation (or an affiliate thereof) that the Board determined to be equivalent in value (as of thedate of such determination or another date specified by the Board) to the per share consideration received by holders of outstandingshares of Common Stock as a result of the Reorganization Event.8.Miscellaneous.(a)No Right To Employment or Other Status. The grant of this option shall not be construed as giving the Participant theright to continued employment or any other relationship with the Company. The Company expressly reserves the rightat any time to dismiss or otherwise terminate its relationship with the Participant free from any liability or claimhereunder, except as otherwise expressly provided herein or provided for in the Letter Agreement.(b) No Rights As Stockholder. Subject to the provisions of this option, the Participant shall not have any rights as astockholder with respect to any shares of Common Stock to be distributed with respect to this option until becoming the record holderof such shares.(c) Entire Agreement. This Agreement, together with the Letter Agreement, constitute the entire agreement between theparties, and supersede all prior agreements and understandings, relating to the subject matter hereof.(d) Amendment. Except with respect to any vesting terms set forth in the Letter Agreement, the Board may amend, modify orterminate this Agreement, including but not limited to, substituting another option of the same or a different type and changing the dateof exercise or realization. Notwithstanding the foregoing, the Participant’s consent to such action shall be required unless (i) the Boarddetermines that the action, taking into account any related action, would not materially and adversely affect the Participant, or (ii) thechange is permitted under Section 7 and the Letter Agreement.(e) Acceleration. The Board may at any time provide that this option shall become immediately exercisable in whole or inpart, free of some or all restrictions or conditions, or otherwise realizable in whole or in part, as the case may be.(f) Conditions on Delivery of Stock. The Company will not be obligated to deliver any shares of Common Stock pursuant tothis Agreement until (i) all conditions of this Agreement have been met to the satisfaction of the Company, (ii) in the opinion of theCompany’s counsel, all other legal matters in connection with the issuance and delivery of such shares have been satisfied, includingany applicable securities laws and regulations and any applicable stock exchange or stock market rules and regulations, and (iii) theParticipant has executed and delivered to the Company such representations or agreements as the Company may consider appropriateto satisfy the requirements of any applicable laws, rules or regulations.(g) Administration by Board. The Board will administer this Agreement and may construe and interpret the terms hereof. Subject to the terms and provisions of the Letter Agreement, the Board may correct any defect, supply any omission or reconcile anyinconsistency in this Agreement in the manner and to the extent it shall deem expedient to carry the Agreement into effect and it shallbe the sole and final judge of such expediency. No director or person acting pursuant to the authority delegated by the Board shall beliable for any action or determination relating to or under this Agreement made in good faith.(h) Appointment of Committees. To the extent permitted by applicable law, the Board may delegate any or all of its powershereunder to one or more committees or subcommittees of the Board (a “Committee”). All references herein to the “Board” shall meanthe Board or a Committee to the extent that the Board’s powers or authority hereunder have been delegated to such Committee.(i) Severability. The invalidity or unenforceability of any provision hereof shall not affect the validity or enforceability of anyother provision hereof, and each such other provision shall be severable and enforceable to the extent permitted by law.(j) Governing Law. This Agreement shall be governed by and interpreted in accordance with the laws of the State ofDelaware, excluding choice-of-law principles of the law of such state that would require the application of the laws of a jurisdictionother than the State of Delaware.(k) Counterparts. This Agreement may be executed in one or more counterparts, each of which shall be deemed to be anoriginal but all of which together will constitute one in the same instrument.[Remainder of Page Intentionally Blank]The Company has caused this option to be executed by its duly authorized officer. SESEN BIO, INC. By: /s/ Thomas R. Cannell Name: Thomas R. Cannell, D.V.M. Title: President & Chief Executive OfficerThe undersigned hereby accepts the foregoing option and agrees to the terms and conditions thereof.PARTICIPANT /s/ Dennis Kim Dennis Kim, M.D., MPHAddress: 1 McVickers LaneMendham, New Jersey 07945 - 1 - Exhibit 10.34[***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYMASTER BIOPROCESSING SERVICES AGREEMENTThis Master Bioprocessing Services Agreement dated October 4, 2018 (the “Effective Date”) is between Sesen Bio, Inc. f/k/a ElevenBiotherapeutics, Inc. (“Sponsor”), a Delaware corporation, with offices at 245 First Street, Suite 1800, Cambridge, MA 02142 and FUJIFILMDiosynth Biotechnologies U.S.A., Inc., a Delaware corporation (“Fujifilm” or “FDBU”), having its principal place of business at 101 J. MorrisCommons Lane, Morrisville, NC 27560, (each a “Party”, and collectively, the “Parties”).Sponsor desires Fujifilm to perform services in accordance with the terms of this Agreement and the Scope (as hereinafter defined) related to theproduction of Product, and Fujifilm desires to perform such services;In consideration of the above statements, which form part of this Agreement, and other good and valuable consideration, the sufficiency andreceipt of which are hereby acknowledged, the Parties hereto agree as follows:Definitions:“Acceptance” or “Accepted” shall mean Sponsor’s acceptance of a Batch after receipt of the Batch Packet, as set forth in Section 6 of thisAgreement and the Quality Agreement.“Actual Expenditure” shall have the meaning set forth in Section 5(b).“Additional Consumables” shall have the meaning set forth in Section 5(b).“Affiliate” shall mean in relation to either Party, any corporation, association or other business entity that directly or indirectly controls, is controlledby or is under common control with such Party, and “control” shall mean the legal power to direct or cause the direction of the general managementand policies of such entity whether through the ownership of at least 50% of voting securities or capital stock of such business entity or any othercomparable equity or ownership interest with respect to a business entity other than a corporation, by contract or otherwise.“Agreement” shall mean this Master Bioprocessing Services Agreement, each Scope that has been executed, all attachments, and the QualityAgreement.“API” shall have the meaning set forth in the Quality Agreement.“Applicable Laws” shall mean all applicable laws, statutes, regulations, guidelines, guidance, and ordinances of the relevant governmental orregulatory authorities, including cGMP, of: (a) the United States; (b) Canada; (c) the United Kingdom; and (d) the European Union, with respect to aParty, the Facility, Product, Program, or the performance any other obligations under this Agreement, whether in effect as of the Effective Date oradopted thereafter, including any successor laws, regulations or guides.“Approved Supplier” shall have the meaning set forth in the Quality Agreement.“Assumptions” shall have the meaning set forth in Section 7(a).“Background Intellectual Property” shall mean any Intellectual Property: (a) owned or licensed to a Party as of the Effective Date; or (b)thereafter acquired or developed by a Party independently of this Agreement and without use of or reference to any Confidential Information of theother Party.“Batch” shall mean a specific quantity of Product that is intended to have uniform character and quality, within specified limits, and is producedaccording to a single manufacturing order during the same cycle of manufacture. In the case of continuous production, a Batch may correspond toa defined fraction of the [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYproduction. The Batch size can be defined either by a fixed quantity or by the amount produced in a fixed time interval, and shall include, forclarity, any Intermediates of API/Drug Substance.“Batch Packet” shall mean the package of relevant documentation to be transferred to Sponsor in relation to a cGMP Batch as detailed in theQuality Agreement or Scope.“cGMP” shall mean the current regulatory requirements for Good Manufacturing Practice pursuant to: (a) the U.S. Federal Food, Drug, andCosmetic Act as amended (21 USC 301 et seq.); (b) U.S. regulations in Title 21 of the U.S. Code of Federal Regulations Parts 210, 211, 600 and610; (c) the equivalents thereof in Canada; (d) Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2015 part II: BasicRequirements for Active Substances used as Starting Materials; (e) International Conference on Harmonization (ICH) Guidance for Industry Q7Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients; and (f) Directive 2003/94/EC of 8 October 2003 laying down theprinciples and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products forhuman use and the European Commission's guidelines “The rules governing medicinal products in the European Union”, Volume 4, “EU Guidelinesto Good Manufacturing Practice - Medicinal Products for Human and Veterinary Use”, in each case including successor laws, regulations orguides.“cGMP Batch” shall mean a Batch identified in a Scope manufactured at a Facility which is intended to be manufactured under cGMP conditionsand subject to Disposition in each case in accordance with cGMP.“CMC Section” shall have the meaning set forth in Section 3(c).“Change Order” shall have the meaning set forth in Section 7(b).“Claim” shall have the meaning set forth in Section 16(a).“Competitive Product” shall mean [***].“Confidential Information” shall have the meaning set forth in Section 8(h).“Consumables Advance Payment” shall have the meaning set forth in Section 5(b).“Debarment” shall have the meaning set forth in Section 17(c).“Delay” shall mean a delay caused or requested by Sponsor to the scheduled start of Batch manufacturing under a Scope, which delay is notattributable to a Force Majeure or any negligent actions or omissions of the Fujifilm Group or Subcontractors (or any Fujifilm Fault).“Disposition” shall mean the process by which all documentation (including executed Batch records) related to cGMP manufacture of each Batchis reviewed and approved by Fujifilm and a Batch Packet is compiled and submitted to Sponsor for Acceptance or rejection thereof in accordancewith the Quality Agreement.“Dispute” shall mean any controversy or claim arising out of, relating to or in connection with any provision of this Agreement, including anysubsequent amendments, or the validity, enforceability, construction, performance or breach hereof (and including the applicability of arbitration toany such controversy or claim).“Drug Product” shall have the meaning set forth in the Quality Agreement.“Drug Substance” shall have the meaning set forth in the Quality Agreement.2CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPY“Effective Date” shall have the meaning set forth in the preamble.“Engineering Batch” shall mean a Batch manufactured in a Facility using the Process and released Process Consumables, but not intended to bea cGMP Batch and not suitable for use in humans. Engineering Batch is not a subject to Disposition, but is subject to review for compliance withthe mutually agreed upon draft specifications.“Execution Factor” shall mean [***].“Facility” shall mean the facilities where services are being performed as described in the Scope, which may include Fujifilm’s development and/ormanufacturing facilities in RTP, North Carolina, US and/or development and/or manufacturing facilities at Belasis Avenue, Billingham, UK, and/orin College Station, Texas.“Facility or Equipment Modification” shall mean a modification to the Facility or to equipment (including Process-specific qualification andinstallation of existing equipment) required in order to site a Process in the Facility as detailed in the applicable Scope or Change Order.“FDBK” shall mean FUJIFILM Diosynth Biotechnologies UK Limited of Belasis Avenue, Billingham, TS23 1LH.“FDBT” shall mean FUJIFILM Diosynth Biotechnologies Texas, LLC a Texas Limited Liability Company, having its principal place of business at100 Discovery Drive, Suite 200, College Station, Texas 77845.“Fujifilm” or “FDBU” shall have the meaning set forth in the preamble.“For Cause Audit” shall mean any for cause audit or any follow-up audit of a previous audit during which material deficiencies were identified.“Force Majeure” shall mean any cause beyond the reasonable control of the Party in question which for the avoidance of doubt and withoutprejudice to the generality of the foregoing shall include governmental actions, war, riots, terrorism, civil commotion, fire, flood, epidemic, labourdisputes (excluding labour disputes involving the work force or any part thereof of the Party in question), restraints or unavoidable delays affectingshipping or carriers, inability or unavoidable delay in obtaining supplies of adequate or suitable materials, currency restrictions, and acts of God,but shall not include the failure of Drug Product in clinical trials or failure of Drug Product to gain regulatory approval.“Fujifilm Confidential Information” shall mean all Confidential Information whether disclosed in writing, verbally, by way of sample or by anyother means and whether directly or indirectly, by or on behalf of Fujifilm to Sponsor in connection with this Agreement, including BackgroundIntellectual Property of Fujifilm and Process Inventions, but excluding Sponsor Inventions, except to the extent Fujifilm Confidential Information isincorporated into Fujifilm Deliverables.“Fujifilm Deliverables” shall mean Process specification, Batch records, Product (including Product samples), Work Output, technical reports,risk assessments, or other deliverables of a Program to be provided by Fujifilm under a Scope.“Fujifilm Fault” shall mean [***].“Fujifilm Group” shall have the meaning set forth in Section 16(b).“GMP At-Risk Run” shall have the meaning set forth in Section 6(c).3CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPY“ICC” shall have the meaning set forth in Section 15(c).“Impasse Notice” shall have the meaning set forth in Section 7(b).“Indemnified Party” shall have the meaning set forth in Section 16(c).“Indemnifying Party” shall have the meaning set forth in Section 16(c).“Intellectual Property” shall mean all intellectual property rights, including trademarks, copyrights, know-how, data, designs, procedures andprocesses, and patents, whether registered or unregistered, and all applications and registrations therefor.“Intermediate” shall have the meaning set forth in the Quality Agreement.“Joint Steering Committee” or “JSC” shall have the meaning set forth in Section 22(a).“Latent Defect(s)” shall mean defects in a Batch that Sponsor can demonstrate in accordance with Section 6(b) were present at the time ofAcceptance but were discovered after Acceptance (but within the time frame set forth in Section 6) that render the Batch as Non-ConformingBatch.“Loss” shall have the meaning set forth in Section 16(a).“Manufacturing Stage” or “Manufacturing Stages” shall mean a Stage or Stages of a Program identified in the applicable Scope during whichproduction, testing and Disposition (where applicable) of an Engineering Batch or cGMP Batch is intended to take place, including preproductionactivities; Facility change–over, setup, and cleaning before, between and after Batch manufacturing.“Non-Conforming Batch” shall mean [***].“Party” or “Parties” shall have the meaning set forth in the preamble.“Payment Schedule” shall mean the schedule applicable to a Program and attached to and forming part of the applicable Scope.“Personnel” shall have the meaning set forth in Section 1(f).“Pre-PPQ Run” shall have the meaning set forth in Section 7(b).“Process” shall mean the process for manufacture of a Product.“Process Consumable” shall mean a consumable item used or intended for use in a Program, including polyethylene glycol (PEG), reagents(including analytical reagents), Raw Materials, packaging components, chromatography resins, filters, filtration membranes, media, buffer bags,refold bags, tubing, hoses, disposable analytical test kits, in-process measurement probes, columns (including analytical columns) and disposablecontainers.“Process Invention” shall mean all Intellectual Property generated, in whole or in part, by or on behalf of Fujifilm or Personnel or Subcontractors inthe conduct of the Program that relates to Fujifilm’s manufacturing and analytical methods that are of a general applicability and are both: (a) of ageneral nature and not specific to a Program, Product, Process, or other Fujifilm Deliverables; and (b) generated without use of SponsorConfidential Information (including Sponsor Materials).“Process-Specific Consumable” shall mean a Process Consumable which is required to operate the Process and which is specific to theProcess or a Process Consumable which is required in such large4CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYvolumes as would not be possible for Fujifilm to consume during other manufactures and/or within the shelf life of such Process Consumable.“Process-Specific Equipment” shall mean an item of equipment which is required to operate the Process and which is specific to the Process.“Product” shall mean: (a) API/Drug Substance of Vicinium; (b) Drug Product known as Vicinium; or (c) Intermediate(s) of API/Drug Substanceand/or Drug Product known as Vicinium, in each case as specified in the applicable Scope.“Program” shall mean the services to be performed according to a Scope executed under this Agreement.“Program Assumptions” shall have the meaning set forth in Section 7(a).“Program Manager” shall have the meaning set forth in Section 22(b).“Program Modification” shall have the meaning set forth in Section 7(a).“Program Schedule” shall mean the anticipated timeline for performance of each Stage of the Program.“Quality Agreement” shall mean the quality agreement to be entered into by the Parties, which addresses regulatory and quality obligations of theParties, as such Quality Agreement may be amended or replaced from time to time.“Raw Material” shall have the meaning set forth in the Quality Agreement.“Regulatory Authorities” shall mean any national, regional, state or local regulatory agency, commission, or other governmental entity withauthority over the Product or the Parties within Canada, the United States, the U.K., or the European Union, including the United States Food andDrug Administration or any successor agency or authority thereto (the “FDA”), Health Canada or any successor agency or authority thereto, thecompetent authorities of the EU member states, and the European Medicines Agency or any successor agency or authority thereto (the “EMA”).“Rules” shall have the meaning set forth in Section 15(c).“Scope” shall mean a written scope of work setting out in detail the work to be undertaken during a Program, which scope shall identify theapplicable Program and specify the services to be provided under such Program, the anticipated timeline for performance of each Stage of theProgram, each Party’s responsibilities in connection with the Program, Sponsor Deliverables, Fujifilm Deliverables, the fees and PaymentSchedule with respect to such Scope, and any additional provisions applicable to the Program.“Special Waste” shall mean a waste or effluent which is required to be collected in a special container for external disposal as detailed in theapplicable Scope or Change Order.“Speculative Buying” shall have the meaning set forth Section 5(b).“Sponsor” shall have the meaning set forth in the preamble.“Sponsor Confidential Information” shall mean: (a) all Confidential Information whether disclosed in writing, verbally, by way of sample or by anyother means and whether directly or indirectly, by or on behalf of Sponsor to Fujifilm Group or Subcontractors in connection with this Agreement,including Background Intellectual Property of Sponsor and Sponsor Deliverables; and (b) Sponsor Inventions, except to the extent FujifilmConfidential Information is incorporated into Fujifilm Deliverables.5CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPY“Sponsor Deliverables” shall mean those Process Consumables and other information and materials required to be provided by Sponsor inconnection with a Program as detailed in the applicable Scope, including any Sponsor Materials.“Sponsor Group” shall have the meaning set forth in Section 16(a).“Sponsor Inventions” shall mean all Intellectual Property, other than a Process Invention, generated in the conduct of a Program, related to aProduct, or using any Sponsor Confidential Information, including any modifications, improvements, or derivatives to Sponsor Materials, generatedin whole or in part, by Fujifilm Group, Subcontractors, or Sponsor, whether alone or in conjunction with others, including the Process and FujifilmDeliverables.“Sponsor Material” shall mean all tangible biological materials provided to Fujifilm by or on behalf of Sponsor in connection with this Agreement,including any cell banks, plasmids, and their progeny and derivatives, reagents, reference standards, assays and media.“Sponsor Process Inventions” shall mean Sponsor Inventions that are of general applicability and are both: (a) of a general nature and notspecific to a Program, Product, Process, or other Fujifilm Deliverables; and (b) inoperable without use of Sponsor Confidential Information(including Sponsor Materials).“Stage” shall mean a stage of the Program as described in the Scope.“Subcontracted Work” shall mean work involving handling, testing or processing of Product subcontracted by Fujifilm as set forth in the Scopeand the cost of delivery of material to and from such contractors.“Work Output” shall have the meaning set forth in Section 9(a).Section 1.Scope of Work/Performance of Programsa)From time to time, at Sponsor’s request, the Parties will agree on Programs to be undertaken with respect to Product. Each Program willbe subject to a separate, numbered Scope (being “Scope of Work #1”, “Scope of Work #2”, etc.). A Program may be subject to a single ormultiple Scopes. Each Scope shall be signed by Sponsor and Fujifilm once its terms are agreed and, on signature, the Scope shall besubject to the terms of and incorporated into this Agreement. For clarity, no Scope shall take effect unless and until executed in writing byan authorized representative of each Party, and no changes shall be made to the Scope until execution of a Change Order in accordancewith Section 7 of this Agreement. Fujifilm shall have no obligation to provide services under this Agreement, and Sponsor shall have noobligations to provide any Sponsor Deliverables or make any payments under this Agreement, unless and until the Parties have executeda Scope or Change Order, as applicablea)Fujifilm will diligently perform Programs for Sponsor and provide the Fujifilm Deliverables in accordance with the terms and conditions ofthis Agreement (which includes the applicable Scope and the Quality Agreement and all Applicable Laws) and shall use commerciallyreasonable efforts to perform the Programs within the timeline for performance of the applicable Stage in the Program Schedule.b)Unless expressly stated otherwise in the applicable document, terms defined in the terms and conditions of this main Agreement shallhave same meaning when used in the Scope or Quality Agreement.6CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYc)Each Party: (a) shall perform its obligations as set forth in this Agreement; (b) shall support and cooperate with the execution of theProgram; and (c) shall not engage in any negligent act or omission which may reasonably be expected to prevent or delay the successfulexecution of the Program.d)Fujifilm will: (d) provide Sponsor with written and/or oral reports as set forth in the applicable Scope on the status of the Program; and (e)cooperate with Sponsor’s representatives and third party vendors who are assisting in the development and commercialization of theProduct.e)Fujifilm will have the right to subcontract aspects of a Program through third parties as set forth in the Scope, provided further that: (1)Fujifilm remains fully and primarily responsible to Sponsor for the performance of, and acts and omissions of, such third party(ies), as ifcommitted by Fujifilm; and (2) in no event shall Sponsor have any liability to any third party for any failure of Fujifilm to perform under itsagreement with such third party, including any failure to pay any amounts due to such third party. Without limiting the foregoing, Fujifilmshall be responsible for the conduct of all suppliers, agents, subcontractors (collectively, “Subcontractors”), and employees (of itself orits Affiliates who perform services under this Agreement) (“Personnel”) who provide services in support of a Program hereunder, andFujifilm shall only assign and use qualified and experienced Personnel and Subcontractors to support the Program.f)The Agreement may be amended at a later date to include FDBU's Affiliate(s): FDBK and/or FDBT.Section 2. Sponsor Deliverables and Fujifilm Deliverablesa)As further set forth in the applicable Scope, Sponsor will provide Fujifilm with those Sponsor Deliverables described in the applicableScope and use commercially reasonable efforts to do so in accordance with the timelines set forth therein. Failure by Sponsor to provideSponsor Deliverables within the timeframe set forth in the Scope for performance of such Stage as reasonably necessary to execute theProgram without delay may result in additional charges to Sponsor as further described in Section 19 of this Agreement and a possibledelay in meeting Program objectives. Sponsor shall request and obtain a shipping authorization from Fujifilm prior to shipping any SponsorDeliverables.b)Title to Sponsor Deliverables shall remain with Sponsor. Fujifilm shall not, in whole or part, sell, pledge, hypothecate, dispose of, orotherwise transfer any interest in or to Sponsor Deliverables except as expressly permitted in the applicable Scope, and Fujifilm shall useSponsor Deliverables solely for purposes of performing the relevant Program in accordance with the applicable Scope. Fujifilm shall notand shall not permit Sponsor Deliverables to be altered, disassembled, reverse engineered or in any way tampered with, except wherenecessary to perform the Program and/or as provided in the applicable Scope. Fujifilm shall provide safe and secure storage conditions forSponsor Deliverables while they are at Fujifilm’s location, including storing such Sponsor Deliverables in accordance with any appropriateconditions, any instructions provided by or on behalf of Sponsor, and all Applicable Laws. Fujifilm will, on Sponsor’s reasonable requestand no more than on a quarterly basis, provide Sponsor with updates on the quantity of any remaining Sponsor Deliverables in inventory topermit Sponsor to timely provide any new Sponsor Deliverables required to execute the Program. Subject to [***] of this Agreement, [***].c)Fujifilm will procure all Process Consumables (except those to be provided by Sponsor under the applicable Scope) in accordance with theapplicable Scope to execute the Program. Title for all such Process Consumables shall remain with Fujifilm unless and until use in aProgram. Fujifilm will maintain, store, and test all Process Consumables as required by the specifications in the7CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYapplicable Scope, and Applicable Laws (including cGMP), and otherwise in compliance with this Agreement.d)Fujifilm: (f) will not use any Process-Specific Consumables or Process-Specific Equipment other than to perform the Program inaccordance with this Agreement; and (g) unless otherwise specified in a Scope or another written agreement, will be responsible formaintaining and repairing any such Process-Specific Equipment at Sponsor’s cost and expense.e)Fujifilm will provide Sponsor with the Fujifilm Deliverables as described in the applicable Scope and using commercially reasonable effortsto meet the timeline for the applicable Stage as described in the Program Schedule. Unless Sponsor requests such delivery, Fujifilm willnot deliver any Fujifilm Deliverables that do not meet their applicable specifications.Section 3. Compliance with Applicable Lawsa)Fujifilm shall, at its sole cost and expense, operate a Facility in accordance with Applicable Laws for all aspects of the Program. Fujifilmshall secure and maintain, at its sole cost and expense, any registrations, approvals, permits, authorizations, and licenses as are requiredby Applicable Laws for Fujifilm to perform its obligations under this Agreement, including, all required licenses, permits, registrations,approvals, and authorizations required in connection with any hazardous materials or waste and shall take reasonably necessary actionsto pass any inspections or audits by the applicable Regulatory Authorities. All Product requested by Sponsor under a Scope shall bemanufactured solely by Fujifilm at the applicable Facility. In addition, Fujifilm shall perform each Program in compliance in all respectswith Applicable Law related to the Product’s clinical and/or commercial phase. Fujifilm shall monitor and maintain reasonable recordsrespecting its compliance with Applicable Laws including cGMPs, including the process of establishing and implementing the operatingprocedures, equipment files, and the training of Personnel and Subcontractors as are reasonably necessary to assure such compliance.b)Sponsor acknowledges that Fujifilm has consulted with Sponsor in designing each Program in a manner consistent with current ApplicableLaws governing the approval of an investigational product for marketing in the U.S. and those governing the grant of a marketingauthorization for a medicinal product in Europe and Canada, and the Assumptions. Notwithstanding the foregoing, Fujifilm does not warrantthat a Program and/or a Program’s results will satisfy the requirements of any Regulatory Authorities at the time of submission of suchProgram results to such Regulatory Authorities; provided however, that the foregoing shall not: (h) limit Fujifilm’s diligence obligations orits quality obligations with respect to maintaining a cGMP compliant Facility or otherwise under the Quality Agreement; or (i) apply wherefailure to satisfy the requirements of the Regulatory Authority relates to any deficiencies with the Facility, Fujifilm’s quality systems, orany other requirements imposed on Fujifilm by a Regulatory Authority or Applicable Law, including Fujifilm’s obligations under Section 3(a)of this Agreement.c)Sponsor shall have the right and responsibility for determining regulatory strategy, decisions and actions relating to a Program and theapplicable Product and, subject to each Party’s contractual obligations under this Agreement, Fujifilm shall have the right andresponsibility for determining regulatory strategy, decisions and actions to the extent relating to: (j) the Facility in which Product ismanufactured; (k) Fujifilm’s quality systems; (l) any requirement imposed on Fujifilm by a Regulatory Authority; or (m) any othercommitments made by Fujifilm prior to the Effective Date of this Agreement; provided however, that in all cases, (x) such regulatorystrategy, decisions and actions are in compliance with Applicable Laws and do not violate this Agreement, and (y) Fujifilm shall not makeany change to its regulatory filings and shall not make any changes to its Facility, in either case, which would have a material adverseimpact on the Program or Product without Sponsor’s prior consent, not to be unreasonably withheld, delayed or conditioned. Withoutlimiting the foregoing, Fujifilm will not implement any modification, material or otherwise, to the Process,8CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYProduct specifications or associated Batch records without Sponsor’s prior written request and approval and complying with the processesfor requesting and implementing any such changes as set forth in the Quality Agreement. The Parties will cooperate in good faith, andSponsor will provide Fujifilm with a reasonable opportunity to review and comment on the chemistry, manufacturing, and control section(“CMC Section”) of applicable regulatory submission for the Product manufactured by Fujifilm, which such comments Sponsor shallconsider in good faith. Sponsor shall not knowingly include any erroneous information regarding Fujifilm, including, its Facilities, equipmentor processes, in the CMC Section. Fujifilm hereby represents that no requirement imposed on Fujifilm by a Regulatory Authority or anyother commitments made by Fujifilm, in each case, as of the Effective Date, shall prevent or delay Fujifilm from performing the Programor otherwise complying with its obligations hereunder.d)Should any Applicable Laws relating to a Program or Product change, Fujifilm will, in a timely manner, use reasonable efforts to satisfy thenew requirements. In the event that compliance with such new regulatory requirements necessitates a change in a Scope, Fujifilm willdiscuss the same with Sponsor and submit to Sponsor a Change Order to the applicable Scope in accordance with Section 7 of thisAgreement.e)Sponsor should provide Fujifilm with all relevant information of which Sponsor is aware is necessary to carry out the Program inaccordance with the Applicable Laws, and any marketing authorization for the Product. Sponsor should make Fujifilm aware of anyproblems or hazards associated with the Product or Sponsor Deliverables including Sponsor’s prior processing of the Product whichmight pose a hazard to Fujifilm’s premises, equipment, or Personnel, other materials or other products, to the extent that Sponsor is orbecomes aware of any such reasonable possibility (recognizing, however, that Sponsor does not have knowledge of Fujifilm’s premises orPersonnel, or other materials or equipment being used, or products being manufactured by Fujifilm).f)Subject to this Section 3, in the event of a conflict in Applicable Laws, Sponsor and Fujifilm will agree in good faith on which regulationsshall be followed by Fujifilm in its performance of the applicable Program to comply with regulatory requirements and Applicable Laws andadvance such Program.g)Except for approvals and licenses required with respect to the Facility which will be the responsibility of Fujifilm, Sponsor will beresponsible for the preparation and filing of any regulatory filings, if any, and for all contacts and communications with any RegulatoryAuthorities with respect to matters directly relating to any Product. Without limiting Fujifilm’s obligations under this Agreement, includingSection 4 of this Agreement, if: (n) Fujifilm receives any contact or communication from any Regulatory Authority relating in any way tothe Program; or (o) any Regulatory Authority takes any action against Fujifilm for any reason that does or could be reasonably expected tohave an adverse effect on the performance of a Program or Product, including any adverse effect on the Program Schedule, Fujifilm will(a) promptly notify Sponsor and provide Sponsor with copies of the relevant portions of any such communication or information related tosuch regulatory action within [***], to the extent such communication or information are related to the Product, of its receipt of suchcontact and/or communication; (b) consult with Sponsor regarding the response to any inquiry or observation from any RegulatoryAuthority relating to a Program or Product; (c) with respect to matters directly related to the performance of the Program or on a Product,allow Sponsor, at Sponsor’s discretion, to participate in any further contacts or communications relating to a Program or Product, andFujifilm shall otherwise comply with all reasonable requests by Sponsor with respect to any actions to be taken or responses to be madeto any such Regulatory Authority; (d) provide Sponsor with the relevant portions of any final copies of any contacts or communicationspromptly after submission; and (e) timely respond to and correct any deficiencies or issues raised by such Regulatory Authority to ensurethe continuation of the Program in accordance with the Program9CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYSchedule and Applicable Laws; provided further that where such communications relate to a third party’s product, Fujifilm may redactinformation confidential to such third party. Fujifilm will not initiate any contact or communication, whether written or oral, with any suchRegulatory Authority regarding a Program or the Product without the prior written consent of Sponsor, which consent will not beunreasonably withheld.a)Fujifilm shall keep Sponsor fully informed of any notification or other information it receives or becomes aware of, including any Productcomplaints which might affect the marketability, safety or effectiveness of Product and/or which might result in the recall or seizure ofProduct within [***] of receiving such information; provided however that all information concerning suspected or actual product tampering,contamination or Non-Conforming Batches shall be delivered within [***] of receiving or becoming aware of such information (whicheveroccurs first), with such reports made in accordance with requirements set forth in the Quality Agreement. Sponsor retains the authorityand responsibility for communicating any responses thereto with any Regulatory Authorities and/or third parties. Fujifilm shall cooperatefully with Sponsor in dealing with such Product quality issues, and shall take reasonable actions and provide any additional assistanceand information as Sponsor reasonably requests, including promptly investigating and conducting follow up with regard to such qualityissues, and providing any data, information, or other assistance that Sponsor may reasonably require in connection therewith.b)If either Party in good faith determines that a recall or other action involving the Product is warranted, such Party shall, as soon aspossible (but in any event within [***] following such determination), notify the other Party and shall advise such other Party of thereasons underlying its determination that such recall or other action is warranted in accordance with the Quality Agreement. Sponsor shallretain full authority and responsibility for making recall decisions, implementing any necessary actions, and corresponding with theapplicable Regulatory Authorities, and Fujifilm agrees to promptly provide to Sponsor, any data, information, or assistance as reasonablyrequested by Sponsor in connection therewith. For the avoidance of doubt, any recalls shall be handled in accordance with Sponsor’spolicies and procedures. Subject to [***], to the extent that any recalls or other corrective measures are caused by a [***] of theapplicable Scope or the Quality Agreement, [***]. For clarity, Fujifilm shall not be responsible for the costs of a recall that occurs as aresult of a Product’s failure to meet its stability requirement, [***] of the applicable Scope or Quality Agreement.c)Fujifilm will cooperate with Sponsor, at Sponsor’s sole cost and expense, and provide reasonable assistance in connection with informalpresentations, data and information requests, and administrative hearings with any Regulatory Authorities as related to the Program andapplicable Fujifilm Deliverables, including attending meetings as reasonably requested by Sponsor, whether with Regulatory Authorities orwith other consultants that Sponsor may engage in connection with a Product as set forth in the applicable Scope, and for the cost andexpense to be paid by Sponsor set forth therein; provided however, that Fujifilm will provide one (1) electronic copy of any documentswhich may be reasonably required by Sponsor in support of its regulatory filing activities without charge.d)Fujifilm shall be responsible, at Fujifilm’s sole cost and expense, for the generation, collection, storage, handling, transport, and release ofhazardous materials and waste generated by or on behalf of Fujifilm in connection with a Program under this Agreement other than SpecialWaste, unless otherwise specified in a Scope.Section 4. Facility Visits10CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYa)Sponsor Audits and Visits. During the term of this Agreement and for [***] following completion of the last cGMP services performedunder this Agreement, Sponsor shall be entitled to [***] regular audit per [***], and during the term of this Agreement and for [***],Sponsor shall be entitled to an unlimited number of For Cause Audits if Sponsor has a reasonable, good faith basis to request such ForCause Audit. All audits (both regular audits and For Cause Audits) will be conducted during business hours, and upon reasonable priornotice to Fujifilm. Sponsor will have the option, at Sponsor’s expense, to designate certain independent third parties reasonablyacceptable to Fujifilm to verify that the Program is conducted in compliance with the testing and other quality-related requirements of theapplicable Scope and the Quality Agreement (including cGMP). Any additional non For Cause Audits will be charged to Sponsor based ona Change Order in the agreed upon amount, which shall be commensurate with the agreed upon scope of such audit. For clarity, Fujifilmwill not charge Sponsor for any costs or expenses (whether internal or external) related to the regular audit (up to once per [***]) or any ForCause Audits. In addition, Sponsor shall have the right to have up to [***] representatives (or more if mutually agreed) be on-site at theFacility to observe performance of the Program in accordance with the Quality Agreement.b)Regulatory Authority Inspections. Fujifilm shall permit Regulatory Authorities reasonable access to enter those areas of Fujifilm’spremises concerned with the Program for the purpose of observing and inspecting the performance of the Program and ensuringcompliance with this Agreement and Applicable Laws, as well as those books, records, agreements, and other documents of Fujifilmrelated to such Program where such entry is reasonably necessary or mandatory in order for Sponsor to maintain, approve, apply for oramend its regulatory application or approval in respect of the Product or such entry is reasonably necessary or mandatory for either Partyto otherwise comply with Applicable Laws. With respect to any inspections that are related to a Program, Fujifilm will: (p) in the case ofany unannounced inspections, notify Sponsor within [***] of such inspection, and in the case of announced inspections, notify Sponsorwithin [***] of receipt of such notice from a Regulatory Authority; (q) if not prohibited by such Regulatory Authority, permit Sponsor’srepresentatives to be present on site and participate, as appropriate, in such inspections and any wrap-up sessions; and (r) both (x) (inaddition to providing Sponsor with a copy of such documents under Section 3(g)), provide Sponsor a copy of any draft responses or otherany correspondence or formal communications from Fujifilm to such Regulatory Authority for review and comment at least [***] inadvance of sending in such response to the applicable Regulatory Authority, and (y) take, in good faith, Sponsor’s comments into accountprior to sending in such response. To the extent any such inspection is being conducted by a Regulatory Authority (a) as a pre-condition togranting regulatory approval for a Product or (b) arising from a Regulatory Authority’s concerns with a Product and not due to any actionsor omissions of Fujifilm Group or Subcontractors, Sponsor shall pay Fujifilm for such inspection/audit at a mutually agreed upon rate.c)Fujifilm shall fully cooperate in any audit or inspection conducted hereunder, and shall provide reasonable access to any and allemployees, agents and other representatives of Fujifilm and to such notebooks, quality records, and other documents necessary toassess Fujifilm’s compliance with the applicable testing and other quality-related requirements of the Scope and Quality Agreement(including cGMP and Applicable Law). Fujifilm will, at its own cost and expense, promptly correct any Facility or quality systemdeficiencies or breach or violation identified in any audit or inspection conducted by Sponsor or by any Regulatory Authority under thisAgreement. Fujifilm will work in good faith with Sponsor to address any deficiencies related to the Process or Product that are not due to aFujifilm Fault, Execution Factor, or such other identified breach or violation, with such costs and expenses borne by Sponsor as set forthin a Change Order.Section 5. Compensation11CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYa)Sponsor shall make the payments in respect of each Program as set forth in the applicable Payment Schedule (unless otherwise agreedin a Change Order). Except as set forth in the specific Scope, the amounts set forth in the applicable Payment Schedule do not cover[***].b)Additional charges in respect of Process Consumables.(i)Demonstration Stage and/or Product Manufacturing Stage of Process Consumables.(1)Prior to commencing materials procurement, Fujifilm shall prepare bills of material estimating in good faith the ProcessConsumables required for the Product Manufacturing Stage and/or Process Demonstration Run Stage (as identified in theapplicable Scope). On approval of each of these estimates by Sponsor, Fujifilm shall issue invoices in amounts equal to suchestimates, payable in consideration for technical consultancy in relation to purchase of Process Consumables intended to be usedduring demonstration or manufacturing activities (each being “Consumables Advance Payment”).(2)On completion of a Product Manufacturing Stage and/or Process Demonstration Run Stage, Fujifilm shall calculate theexpenditure incurred in respect of Process Consumables actually used during such Stage and any Process Consumablesprocured for use during such Stage as set forth in the estimate but not actually used, and shall first subtract the costs for anyProcess Consumables for which Fujifilm may be responsible under Section 6, and then shall add a sum equivalent to [***] of theexpenditure on all such Process Consumables, the aggregate amounts in each case being referred to as “Actual Expenditure”. Ifthe Actual Expenditure is greater than the corresponding Consumables Advance Payment, Fujifilm shall issue a further invoice fortechnical consultancy in relation to purchase of such Process Consumables for a sum equivalent to such difference; providedhowever, that Fujifilm will not incur any expenses that exceed [***] of the Consumable Advance Payment without Sponsor’s priorwritten consent. In the event the Parties disagree on whether Fujifilm should incur expenses that exceed such [***], the Partieswill discuss in good faith methods of mitigating such costs, including the availability of alternative suppliers for ProcessConsumables. In the event the Parties are unable to timely agree on such mutually agreed upon alternatives, and if additional feesfor Process Consumables are required to progress the Program and Sponsor fails to approve such additional fees within thenecessary time frame to avoid a delay or cancellation in manufacturing, then pursuant to Section 19, applicable cancellation feesmay apply. If the Actual Expenditure is less than the Consumables Advance Payment, Fujifilm shall issue a credit note againstthe earlier invoice for a sum equivalent to the difference (plus the [***] for the technical consultancy fee, if such fee was includedin the Consumables Advance Payment).(ii)Additional Process Consumables for non-manufacturing activities. Fujifilm shall provide a good faith estimate of ProcessConsumables that are required for use in non-manufacturing activities (e.g., analytical work) in any Stage in the Scope. Each month,Fujifilm shall issue an invoice to Sponsor for additional technical consultancy in relation to procurement of additional ProcessConsumables for use during non-manufacturing activities (“Additional Consumables”) during the previous month in amountsequivalent to the expenditure on such Additional Consumables during the previous month, less the costs for any AdditionalConsumables for which Fujifilm is responsible under Section 6, plus [***]; provided however, that Fujifilm will use commerciallyreasonable efforts to not incur any expenses that exceed [***] of the pre-approved estimated expenditure for Additional Consumableswithout Sponsor’s prior written consent. In the event the Parties disagree on whether Fujifilm should12CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYincur expenses that exceed such [***], the Parties will discuss in good faith methods of mitigating such costs, including theavailability of alternative suppliers for such Process Consumables. In the event the Parties are unable to timely agree on suchmutually agreed upon alternatives, and if additional fees for Process Consumables are required to progress the Program and Sponsorfails to approve such additional fees within the necessary time frame to avoid a delay or cancellation in the Program, then pursuant toSection 19, applicable cancellation fees may apply.(iii)Fujifilm will (A) only purchase Process Consumables for Sponsor in such quantities as are reasonably necessary to perform theProgram in accordance with the applicable Scope; (B) not engage in Speculative Buying of any Process Consumables for Sponsor onany level, directly or indirectly, through independent third parties, or through any Affiliate; (C) timely rotate inventory of ProcessConsumables on a first expiry basis; and (D) provide Sponsor with written notice as soon as reasonably practicable in advance of anypurchases of Process Consumables that exceed the caps set forth in subsections (i) and (ii) to allow the Parties to timely, mutuallyand amicably resolve such issue. The term “Speculative Buying” means building a larger inventory supply of Process Consumablesfor Sponsor than is customary in the ordinary course of business to support the normal demand of executing a Program similar inscope to the applicable Scopes executed hereunder. Notwithstanding the foregoing, nothing in this Section shall prohibit Fujifilm frompurchasing common stock items that include Process Consumables (to be shared between clients) at amounts greater thannecessary for Sponsor’s Program; provided, that, Sponsor shall be invoiced only for the portion of such common stock itemspurchased for Sponsor’s Program in accordance with this Section 5(b).c)INTENTIONALLY DELETED.d)Additional Charges in Respect of Subcontracted Work, Process-Specific Equipment, Facility or Equipment Modification, and SpecialWaste. If a Program requires Subcontracted Work, Process-Specific Equipment, Facility or Equipment Modification, or Special Waste,other than those specified in Scope, Fujifilm and Sponsor shall agree in a Scope (or a Change Order) which expenditures are incurreddirectly by Sponsor, which expenditures will be borne by Fujifilm, and for which expenditures Sponsor will compensate Fujifilm, when suchexpenditures are incurred by Fujifilm. Fujifilm shall obtain Sponsor’s approval of the Scope or the Change Order prior to incurring anyexpenditure on Subcontracted Work, Process-Specific Equipment (including cost of installation and qualification thereof), Facility orEquipment Modification, or disposal of Special Waste as the case may be. The Scope or the Change Order shall also specify anynecessary installation and qualification cost for or associated with Process-Specific Equipment or Facility or Equipment Modification, theownership of and liability for any Process-Specific Equipment, any agreements regarding storage and maintenance or Sponsor-ownedProcess-Specific Equipment, and cost of Process-Specific Equipment removal from Fujifilm property or its return to the original state afterthe Program or its relevant part has been completed or terminated, cost of returning Facility to its original stage after the Program or itsrelevant part has been completed or terminated, and the transfer of ownership of Process-Specific Equipment between Fujifilm andSponsor if Sponsor exercises its rights under Section 6(e) below. Any such pre-approved costs incurred by Fujifilm shall be invoiced toSponsor in the same amount as the expenditure which Fujifilm incurs in respect of Subcontracted Work, Process-Specific Equipment(including cost of installation and qualification thereof), Facility or Equipment Modification, and/or disposal of Special Waste, plus a sumequivalent to [***] of such expenditure. Fujifilm shall issue invoices for such technical consultancy services at the time Fujifilm incursexpenditure in respect of the Subcontracted Work, Process-Specific Equipment, Facility or Equipment Modification, and/or disposal ofSpecial Waste as the case may be, which invoice, for clarity, shall not exceed the amount approved by Sponsor under such Scope orotherwise agreed to by the Parties in writing. If Sponsor does not approve an increase to the estimated cost, Fujifilm shall have noobligation to13CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYprocure such items for the Program; provided further, that Fujifilm shall provide all such estimates in good faith and shall use reasonableefforts to mitigate against any increased costs.e)Purchase of Process-Specific Consumables and Process-Specific Equipment. Sponsor shall have an option to purchase from Fujifilm anysuch Process-Specific Consumable or Process-Specific Equipment purchased by Fujifilm, for which Sponsor compensated Fujifilm asspecified above, as such remain following completion of Program or the earlier termination of the applicable Scope or this Agreement.Such Process-Specific Consumable and Process-Specific Equipment shall be purchased for consideration of [***] payable at the time ofsuch sale plus the cost of removal of such Process-Specific Consumable and/or Process-Specific Equipment from Fujifilm’s property. Theoption shall be exercised within (s) [***] following completion of manufacturing for which such Process-Specific Consumable werepurchased or (t) [***] following termination of this Agreement (unless such termination is by Fujifilm for Sponsor’s insolvency underSection 21(b)). Unless otherwise agreed to by the Parties, shipment shall be according to the terms of Section 13, and provided in goodworking order, ordinary wear and tear excepted with respect to any Process-Specific Equipment. Risk in and title thereto shall pass ondelivery. Until such time as Sponsor has exercised such option (or such option has otherwise expired), Fujifilm will not sell, transfer orotherwise convey such Process-Specific Equipment or Process-Specific Consumables to any third party, nor shall Fujifilm place or permitto be placed any lien or encumbrance upon such Process-Specific Equipment or Process-Specific Consumables. In case Sponsor doesnot exercise the aforementioned option within the [***] option period, Fujifilm shall be free to use or dispose of any item(s) of Process-Specific Consumable or Process-Specific Equipment in respect of which Sponsor’s option referred to in this Section 6(e) is not exercised,and Sponsor agrees to pay the reasonable out-of-pocket costs incurred by Fujifilm to dispose of any such Process-Specific Consumableor Process-Specific Equipment.f)Payments. Payments are due [***] from the date an invoice issued by Fujifilm is received by Sponsor, with such invoices being issuedconsistent with the applicable Payment Schedule. Late payments on undisputed amounts are subject to an interest charge of [***] permonth. Unless within [***] of the date of Sponsor’s receipt of the applicable invoice Sponsor has advised Fujifilm in good faith and inwriting the specific basis for disputing an invoice, Sponsor’s failure to pay an undisputed portion of an invoice within [***] of the date ofSponsor’s receipt of the invoice may constitute a material breach of this Agreement. In addition to all other remedies available to Fujifilmin the event of a Sponsor default, if Sponsor fails to make undisputed payments as required hereunder, Fujifilm may refuse to carry outfurther work and/or suspend deliveries of Product or provision of reports until Sponsor makes payment and/or provides assurance offurther or future payment reasonably satisfactory to Fujifilm. Invoices will include a summary of activities completed during the invoiceperiod, including activities completed and an indication of Process Consumables purchased.g)Taxes. Any payment under this Agreement is exclusive of any value added tax (or other tax) that may apply and shall be paid gross,without deductions or set-offs, whether by way of withholding or other income taxes (but excluding taxes on the income of Fujifilm). If anyvalue added tax shall become due, it shall be for the account of Sponsor.Section 6. Non-Conforming Batcha)Upon completion of a cGMP Batch and the determination by Fujifilm that such Batch conforms to cGMP, Product specifications, andspecifications for the testing performed by Fujifilm and listed in the Batch Packet. Fujifilm shall provide Sponsor’s quality assurancedepartment with a Batch Packet and a recommendation for such Batch to be released. Within [***] after Sponsor’s receipt of suchdocumentation and recommendation, Sponsor shall review the Batch Packet to14CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYdetermine, to the extent ascertainable from such documentation, whether or not Sponsor agrees that the Product covered by such BatchPacket conforms to cGMP and to the specifications as set forth above or is a Non-Conforming Batch. Sponsor shall accept the cGMPBatch if such cGMP Batch is not a Non-Conforming Batch.b)In the event Sponsor’s review of a Batch Packet indicates that the relevant Batch may be a Non-Conforming Batch, Sponsor shallpromptly notify Fujifilm’s quality assurance department in writing according to the complaint procedures in the Quality Agreement, andFujifilm shall promptly and diligently initiate an investigation. The Parties shall cooperate in good faith in analyzing and investigating thetest results. The Parties shall mutually determine if the Batch is a Non-Conforming Batch or if further testing is warranted and theconditions for such testing. [***]. If the Parties cannot come to mutual agreement on whether the Batch is a Non-Conforming Batch and/orthe cause of such Non-Conforming Batch, then the Parties shall resolve such dispute in accordance with the Quality Agreement, and if theParties cannot resolve such dispute in accordance with the Quality Agreement, [***].c)The following provisions shall apply if during Disposition of the cGMP Batch or as a result of Sponsor’s review of the applicable BatchPacket and followed investigation, it is ascertained that such cGMP Batch is a Non-Conforming Batch:(i)The Non-Conforming Batch shall not be delivered to Sponsor, unless Sponsor requests delivery of such Non-Conforming Batch inwriting. If Sponsor requests such delivery, the Parties shall agree in a Change Order on terms and limitations of use of such Non-Conforming Batch and, if the non-conformity was due to a Fujifilm Fault, an applicable reduction in compensation to Fujifilm for suchBatch.(ii)Upon Sponsor’s request, Fujifilm shall use commercially reasonable efforts to manufacture and deliver a further cGMP Batch, withcosts allocated as provided below.(iii)The following provisions shall apply if the Non-Conforming Batch arose other than as a result of a [***]:(1)Sponsor shall be obliged to make payment in respect of such Non-Conforming Batch.(2)If Sponsor wishes Fujifilm to manufacture another Batch, such manufacture shall be carried out at a time to be agreed and subjectto agreement of the price payable by Sponsor in respect of such further manufacture (which shall not exceed the price paid forsuch Non-Conforming Batch), with such agreement to be recorded in a Change Order.(iv)If a Batch that was intended to be a cGMP Batch was not completed or if the Non-Conforming Batch arose as a result of a FujifilmFault, Fujifilm shall manufacture a further cGMP Batch at Fujifilm’s cost and expense as soon as reasonably practicable, including thecosts for any Process Consumables needed for such further Batch and the costs to destroy the Non-Conforming Batch.(i)If the Non-Conforming Batch arose as a result of an Execution Factor, Fujifilm shall manufacture a further cGMP Batch at Sponsor’srequest as soon as reasonably practicable. Sponsor shall be responsible for the cost of Process Consumables needed for such furtherBatch, and Fujifilm shall invoice Sponsor for technical consultancy fees related to the procurement of such Process Consumables,and Fujifilm shall be liable for the cost of remanufacture, provided however, that [***]. “GMP At-Risk Run” means the first full scalecGMP Run for the Product, and “Pre-PPQ Run” means the run just prior to the PPQ runs,15CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYwhich is intended to confirm that the manufacturing process, as designed, is capable of reproducible commercial manufacturing.(ii)For clarity, upon Sponsor’s ascertainment that the further cGMP Batch received is not a Non-Conforming Batch under the process setforth in Section 6(a), Sponsor shall be responsible for making final payment for such cGMP Batch. The foregoing obligation does notlimit Sponsor’s right to reject Batches previously Accepted for a Latent Defect in accordance with Section 6(d); it being understoodthat where such rejection is exercised and the fees for the Non-Conforming Batch have been paid in accordance with this Agreement,no further payment will be made by Sponsor upon receipt of the applicable replacement cGMP Batch.(iii)Subject to [***], Sponsor’s sole and exclusive remedy in relation to any Non-Conforming Batch is limited to those remedies set forthin this Section 6.a)For the avoidance of doubt: (u) the Parties will follow the quality procedures set forth in the Quality Agreement while accepting or rejectingthe disputed Batch; and (v) Sponsor shall have the right to reject Batches previously Accepted for a Latent Defect by providing Fujifilmwith written notice of such Latent Defect within [***] of Sponsor’s discovery of such Latent Defect, but no later than [***] followingDisposition of the Batch, in which case the provisions in Section 6(b) of this Agreement shall govern any dispute between the Parties asto whether the Batch was a Non-Conforming Batch, and the provisions of Section 6(c) of this Agreement shall apply with respect to suchNon-Conforming Batch; provided further that if such non-conformance arose from a Fujifilm Fault or Execution Factor, then Fujifilm shallalso pay for the costs to return or destroy such previously Accepted Batch. Unless otherwise agreed by the Parties in writing, Fujifilmshall dispose of any Non-Conforming Batch not requested to be delivered to Sponsor in accordance with all Applicable Laws with respectto such disposal, [***].b)Fujifilm shall conduct all quality control testing of the Sponsor Deliverables and Fujifilm Deliverables to ensure that deliverables deliveredto Sponsor conform to the applicable specifications and comply with Applicable Laws. Without limiting the foregoing, Fujifilm shallestablish, implement, and maintain preventive and corrective procedures in compliance with Applicable Laws to minimize the amount ofNon-Conforming Batches. Fujifilm shall cooperate with Sponsor in determining the cause of any quality problems involving a Batch,identifying corrective actions, and ensuring the implementation and effectiveness thereof. Upon Sponsor’s request and in accordance withany timetables set therein, Fujifilm shall implement such corrective actions, and shall provide Sponsor with written confirmation upon thecompletion thereof. Fujifilm shall notify Sponsor within [***] after the discovery that any lot of shipped Batches, which had previously beenAccepted in accordance with procedures set forth herein, but which is later discovered to be a Non-Conforming Batch, including providingSponsor with all details concerning the nature of any such defect. Fujifilm will make, at its expense, such further internal investigation ofany such Non-Conforming Batch(es) that is appropriate under the circumstances and otherwise consistent with its obligations under thisAgreement (including the Quality Agreement).Section 7. Change Ordersa)The total budget for a Program specified in the applicable Payment Schedule, the individual budget components and the anticipatedtimeline for performance of each Stage of the Program specified in the applicable Scope are subject to a number of general and Programspecific assumptions including the accuracy, timeliness and completeness of Sponsor Deliverables. The assumptions relate to theapplicable Program design and objectives, manpower requirements, timing, capital expenditure requirements (if any), and other mattersrelating to the completion of the Program as further set forth in the applicable Scope (collectively, the “Program16CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYAssumptions”). Fujifilm also assumes that each Party will cooperate and perform its obligations under this Agreement including theapplicable Scope in a timely manner, that no event outside the reasonable control of such Party will occur, including the events describedin Section 18 (Force Majeure), and that there are no material changes to any Applicable Laws, in each case which affect the applicableProgram (the foregoing assumptions together with the Program Assumptions, are collectively, the “Assumptions”). Fujifilm shall prepareeach Scope based on Fujifilm’s skills and experience in bioprocessing products, including the Assumptions; and except with respect toProcess Consumables, which estimates shall be provided in Fujifilm’s good faith efforts, the Scope shall contain a good faith reflection ofthe costs and expenses necessary to conduct each Stage under the Program under such Scope and provide the Fujifilm Deliverablesdescribed therein in light of such Assumptions in accordance with the terms of this Agreement, including all Applicable Laws in effect atthe time of the execution of the Scope. In the event that any of the Assumptions require modification due to unforeseen events or Sponsorrequested changes, or the applicable Program objectives cannot be achieved based on the Assumptions or due to technical challenges(each being a “Program Modification”) then the applicable Scope may be amended as provided in paragraph (b) of this Section 7. For theavoidance of doubt, if Sponsor requests a reduction in the Scope, for example, fewer Batches in a manufacturing campaign or removal ofother Program elements, then cancellation charges may be applicable equivalent to the charges set out in Section 21(f) below in relation tosuch cancelled elements of the Program.b)In the event a Program Modification is identified by Sponsor or by Fujifilm, the identifying Party shall notify the other Party as soon as isreasonably possible. Fujifilm shall provide Sponsor with a change order containing an estimate of the required Program Modifications tothe applicable Program budget, activities and/or estimated timeline for performance as specified in the applicable Scope (“Change Order”)within [***] of receiving such notice or providing such notice to Sponsor. Sponsor shall respond in writing to such Change Order within[***] of receiving such Change Order indicating whether or not it approves the proposed Change Order. If Sponsor does not approve suchChange Order, then Sponsor and Fujifilm shall negotiate in good faith to agree on a Change Order that is mutually acceptable. Ifpracticable, Fujifilm shall continue work on the applicable Program during any such negotiations, but shall not commence work withrespect to the Change Order unless authorized in writing by Sponsor. If a Program Modification results in a Change Order that is notagreeable to both Parties within [***] after issuance of the relevant Change Order and after good faith negotiations in accordance with theprocedures set forth in Section 22, then Fujifilm shall, if reasonably possible, perform the Scope as modified by previously executedChange Orders, if any, without regard to the unresolved Change Order; provided, however, that the estimated timelines and/or ProgramSchedule shall be adjusted to reflect any delay during the negotiation period. In the event that in Fujifilm’s reasonable judgment suchperformance is not possible in accordance with the applicable current Scope and Payment Schedule (subject to the last sentence below),then Fujifilm shall provide written notice to Sponsor of its inability to perform in the absence of an agreed upon Change Order (the“Impasse Notice”). Upon issuance of an Impasse Notice, (i) Sponsor shall have the option of terminating the Scope affected by suchChange Order within [***] following such Impasse Notice; (ii) Fujifilm shall have the option of terminating the Scope affected by suchChange Order within [***] following such Impasse Notice if continuation of such Scope is technically infeasible without approval of theChange Order; and/or (iii) either Party may initiate the arbitration procedures set forth in Section 15 to determine financial responsibility forthe Impasse Notice. In determining relative financial responsibility and damages, if any, the arbitrator(s) shall consider whether theImpasse Notice was justifiable and, if so, which Party should bear financial responsibility for the circumstances underlying the ImpasseNotice based on the reasonableness of each Party in its negotiations with the other Party on such Change Order leading to such ImpasseNotice.Section 8. Confidential Information/Legal Proceedings17CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYa)For the duration of this Agreement and for [***] thereafter, Fujifilm will not, without Sponsor’s prior written permission: (w) use any SponsorConfidential Information for any purpose other than to perform a Program in accordance with this Agreement; or (x) disclose any SponsorConfidential Information to any third party except as permitted under this Agreement. To protect Sponsor Confidential Information, Fujifilmwill: (x) limit dissemination of Sponsor Confidential Information to only those of its (A) Affiliates, Subcontractors and Personnel for whomsuch access and use are required to perform the Program in accordance with this Agreement and/or (B) employees, agents, consultantsand advisers for whom such access and use are required to advise Fujifilm on its legal obligations and rights under this Agreement and ineach of (A) and (B) who are bound by agreements or law sufficient to enable them to comply with the confidentiality and non-disclosureobligations contained herein; and (y) use reasonable precautions to protect the confidentiality of Sponsor Confidential Information fromunauthorized or improper use, loss, destruction, and disclosure, using at a minimum, the same measures and degree of care used toprotect its own proprietary information.b)For the duration of this Agreement and for [***] thereafter, Sponsor will not, without Fujifilm’s written permission: (y) use any FujifilmConfidential Information for any purpose other than to perform its obligations under this Agreement or as permitted under this Agreement;or (z) disclose any Fujifilm Confidential Information to any third party except as permitted under this Agreement. Sponsor will limitdissemination of Fujifilm Confidential Information to only those of its Affiliates and each of their respective subcontractors, employees,agents, consultants and advisers for whom such access and use are required to (A) perform the Program in accordance with thisAgreement and/or (B) advise Sponsor on its legal obligations and rights under this Agreement and who are bound by agreements or lawsufficient to enable them to comply with the confidentiality and non-disclosure obligations contained herein. Sponsor shall use reasonableprecautions to protect the confidentiality of Fujifilm Confidential Information from unauthorized or improper use, loss, destruction, anddisclosure, using at a minimum, the same measures and degree of care used to protect its own proprietary information.c)Permitted Sponsor Uses. Notwithstanding anything in this Agreement to the contrary, Sponsor and its Affiliates and their employees,agents, consultants and advisers, licensees and sublicensees and any of their third party contractors may use or disclose FujifilmConfidential Information to the extent necessary: (aa) in connection with regulatory filings related to Product; or (bb) for the purpose ofexercising its rights or licenses granted under Section 10, including for the purpose of manufacturing Product, having Productmanufactured, or otherwise commercially exploiting any Product (including disclosures to an existing or potential partner, licensee,acquirer, or investor) and in any event, in the case of any disclosures, subject to the imposition of confidentiality no less onerous thanthose of this Agreement. Notwithstanding the foregoing, Sponsor shall not disclose Fujifilm’s pricing for the services intended to beprovided hereunder nor provide the actual proposal provided by Fujifilm to Sponsor to conduct the services intended to be providedhereunder to any third-party contract manufacturing organizations in the biopharmaceutical industry, without in each case, Fujifilm’s priorwritten consent.d)INTENTIONALLY DELETED.e)In the event a Party is required by law, regulation or court order to disclose any Confidential Information of the other Party (including to aRegulatory Authority, in connection with freedom of information legislation or regulations, or in relation to filings with any recognized stockexchange), such Party will be permitted to disclose such Confidential Information provided such Party promptly notifies the owning Partyin writing prior to making any such disclosure in order to allow the owning Party to seek a protective order or other appropriate remedy fromthe competent authority. If disclosure is required in relation to filings with any recognized stock exchange, such Party shall provide a copyof the disclosure to the owning Party at least [***] in advance and18CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYprovide the owning Party with an opportunity to review and redact the information. The Parties will cooperate in good faith to develop afinal disclosure. The compelled Party will cooperate with the owning Party in seeking such order or other remedy. If the owning Party is notsuccessful in precluding the requesting legal body from requiring the disclosure of the Confidential Information, the compelled Party willexercise all reasonable efforts to obtain reliable assurances that confidential treatment will be accorded to such Confidential Information.f)If, despite the efforts undertaken pursuant to Section 8(e) of this Agreement, either Party shall be obliged to provide testimony or recordsconstituting Confidential Information of the other Party in any legal or administrative proceeding, and where such legal or administrativeproceeding does not arise due to any Claims for which the owning Party has a right of indemnity under Section 16 of this Agreement, thenthe Party to whom the Confidential Information belongs shall reimburse the other Party for its out-of-pocket costs incurred in providingsuch testimony or records plus any other mutually agreed upon fee.g)For clarity, Confidential Information containing personal data shall be handled in accordance with Applicable Laws governing the protectionof personal data.h)“Confidential Information” shall mean and include such types of information as: inventions, methods, plans, processes, specifications,characteristics, raw data, analyses, equipment design, trade secrets, costs, marketing, sales, and performance information, includingpatents and patent applications, grant applications, notes, and memoranda, whether in writing or presented, stored or maintainedelectronically, magnetically or by other means; provided, however that information that (cc) is or becomes publicly available through nofault of the non-owning Party; (dd) is disclosed by a third party entitled to disclose it without an obligation of confidentiality to the otherParty; (ee) is already known to the non-owning Party as shown by its prior written records; or (ff) is developed independently of a Programby the non-owing Party without reference to or use of any of the Confidential Information disclosed by the owning Party as shown bywritten records is not Confidential Information.i)Return of Confidential Information. At the written request of the owning Party, the other Party will deliver to the owning Party any tangibleConfidential Information of the owning Party, or destroy, as instructed by the owning Party, any such Confidential Information (in anyelectronic and other copies thereof) in the other Party’s possession or control, and will cease using the owning Party’s ConfidentialInformation, except that: (gg) neither Party will have an obligation to return or to cease to use of any information that such Party has acontinuing license to use under this Agreement; (hh) Sponsor will have no obligation to return or destroy any Fujifilm ConfidentialInformation that is incorporated into Fujifilm Deliverables or that is included in any regulatory filing; and (ii) neither Party will be obligated toreturn or destroy automatically generated copies stored on system back-up media; subject to ongoing compliance with the confidentialityand non-use obligations herein.j)Terms of this Agreement. The terms of this Agreement shall be deemed the Confidential Information of both Parties, and neither Partyshall disclose the existence or terms of this Agreement to any third party without the consent of the other Party, except that the Partiesmay disclose the existence or terms of this Agreement: (jj) pursuant to a public announcement approved under Section 20 of thisAgreement; or (kk) as otherwise permitted pursuant to the remainder of this Section 8.Section 9. Work Outputa)All reports specified in each Scope and other cGMP documentation provided in the Quality Agreement, as well as records, accounts,notes, reports, and Batch data pertaining to a Program, the Product(s), and its and any third party subcontractor’s activities under thisAgreement19CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPY(including the Process) (“Work Output”) will be prepared using Fujifilm’s standard format unless otherwise specified in the relevant Scope.b)Sponsor will be supplied with copies of Work Output generated as a result of each Program as set forth in the Quality Agreement orapplicable Scope. Fujifilm will maintain complete, accurate, and legible records of all Work Output and all quality retains in a secure areaprotected from fire, other natural hazards, theft, and destruction, and Fujifilm shall immediately notify Sponsor in writing in the event of anyloss or destruction of such records or quality retains. All Work Output documentation will be archived by Fujifilm for a period of [***]following completion of the applicable Program unless otherwise required by Applicable Law and quality retains will be archived by Fujifilmfor a period of [***] following completion of the applicable Program unless otherwise required by Applicable Laws. Upon completion of theapplicable retention period: (ll) some or all of the Work Output and quality retains will be sent to Sponsor, and a mutually agreed uponreturn fee will be charged; or (mm) Sponsor may elect to have some or all of the materials retained in the Fujifilm archives for an additionalperiod of time at a mutually agreed upon additional cost to Sponsor; or (nn) Sponsor may choose to have Fujifilm dispose of some or all ofWork Output and quality retains samples at a mutually agreed disposal charge. Notwithstanding the foregoing, Fujifilm will continue toretain such written materials and quality retains as required by Applicable Laws pertaining to such activities as well as for archivalpurposes; provided that such copy remains subject to the confidentiality obligations contained herein. In no event will Fujifilm dispose ofany such materials without first giving Sponsor [***] prior written notice of its intent to do so and complying with any directions or writtenrequests provided by Sponsor. If Sponsor does not reply to Fujifilm’s notification within such [***] period, Fujifilm may take any of theabove actions (return, retain or dispose) at Fujifilm’s sole but reasonable option and at Sponsor’s reasonable expense.Section 10. Inventions and Patentsa)Background Intellectual Property. Nothing in this Agreement shall affect the ownership of any Background Intellectual Property of eitherParty. Without limiting the foregoing, nothing contained in this Agreement, nor the disclosure nor provision to Fujifilm of any ConfidentialInformation shall be deemed to transfer or grant to Fujifilm, or any other person or entity, any right, title, interest, or license in, to or underany Intellectual Property or other right Sponsor, including any rights in or to any Sponsor Materials or any Products, provided however,that Sponsor hereby grants Fujifilm a limited, non-transferable, non-exclusive license to Sponsor’s Background Intellectual Property solelyto the extent necessary for Fujifilm to perform each Program in accordance with the applicable Scope, which license shall last for the termof the applicable Scope.b)Sponsor Inventions. Sponsor Inventions shall be owned solely by Sponsor and shall be Sponsor Confidential Information. Fujifilm willpromptly disclose all Sponsor Inventions to Sponsor in writing. Fujifilm hereby assigns: (oo) all right, title and interest throughout the worldin and to the Sponsor Inventions to Sponsor, including all Intellectual Property; and (pp) all rights of action and claims for damages andbenefits arising due to past and present infringement of said rights to Sponsor. If Sponsor requests and at Sponsor’s expense, Fujifilm willcooperate and execute any and all applications, assignments or other instruments and give testimony which shall be necessary to applyfor and obtain Letters of Patent of the U.S. or of any equivalent patent in any other country, and other documents reasonably necessaryfor Sponsor to secure, perfect, effectuate and preserve its rights in and to Sponsor Inventions, and Sponsor shall compensate Fujifilm forthe time devoted to such activities and reimburse it for its reasonable expenses incurred in respect of such cooperation at a mutuallyagreed upon rate. For Sponsor Inventions assigned pursuant to this section, Sponsor shall provide Fujifilm a limited, non-transferable, non-exclusive, royalty-free license solely to the extent necessary for Fujifilm to perform each Program in accordance with the applicableScope, which license shall last for the term of the applicable20CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYScope. In addition, Sponsor hereby grants Fujifilm a royalty-free, non-exclusive, license, with the right to grant sublicenses, to useSponsor Process Inventions to manufacture products other than (x) Product; (y) any Competitive Product or (z) any product produced from(x) or (y). For the avoidance of doubt, the foregoing license in this Section 10(b) does not grant Fujifilm any rights under any other SponsorInvention or Sponsor’s Background Intellectual Property (or Sponsor Materials).c)Process Inventions. All Process Inventions shall be owned solely by Fujifilm and shall be Fujifilm Confidential Information. Fujifilm herebygrants to Sponsor a perpetual, world-wide, royalty-free, non-exclusive, sub-licensable license under such Process Inventions for Sponsorto disclose, manufacture, have made, modify, use, perform, and otherwise exploit (a) the Process Invention and (b) any FujifilmConfidential Information including Background Intellectual Property incorporated into Sponsor Inventions, in each case, in connection withthe use, further development, manufacture and commercial exploitation of any such Products (including any products within the Product’slifecycle). If Fujifilm requests and at Fujifilm’s expense, Sponsor will execute any and all applications, assignments or other instrumentsand give testimony which shall be necessary to apply for and obtain Letters of Patent of the U.S. or of any equivalent patent in any othercountry with respect to the Process Invention and Fujifilm shall compensate Sponsor for the time devoted to such activities and reimburseit for its reasonable expenses incurred in respect of such cooperation at a mutually agreed upon rate.d)Data. Fujifilm reserves the right to use data generated or obtained during the course of a Program to support applications necessary toapply for and obtain Letters of Patent of the U.S. or of any equivalent patent in any other country with respect to Process Inventions solong as: (qq) no Sponsor Confidential Information is disclosed in any such application; and (rr) Fujifilm notifies Sponsor [***] in advance ofits intent to file such application or other instrument.a)Fujifilm has obtained, or will obtain prior to engaging any Personnel or Subcontractors (including for clarity, any Affiliates), writtenagreements under which such Personnel or Subcontractors (or Affiliate) (i) assign all of their rights in any Sponsor Invention generatedunder a Program to Fujifilm to effectively vest in Fujifilm the full right and authority to assign Sponsor Inventions to Sponsor and (ii) grantthe necessary rights to Fujifilm to enable Fujifilm to grant the licenses under Process Inventions granted to Sponsor hereunder; and (iii)cooperate to execute any documents to confirm or perfect such assignments.Section 11. Independent ContractorFujifilm shall perform each Program as an independent contractor of Sponsor and shall have complete and exclusive control over its facilities,equipment, employees and agents. The provisions of this Agreement shall not be construed to establish any form of partnership, agency or otherjoint venture of any kind between Fujifilm and Sponsor, nor to constitute either Party as the agent, employee or legal representative of the other.All persons furnished by either Party to accomplish the intent of this Agreement shall be considered solely as the furnishing Party's employees oragents and the furnishing Party shall be solely responsible for compliance with all laws, rules and regulations involving, but not limited to,employment of labor, hours of labor, working conditions, workers' compensation, payment of wages, and withholding and payment of applicabletaxes, including income taxes, unemployment taxes, and social security taxes.Section 12. Insurancea)Fujifilm shall secure and maintain in full force and effect throughout the performance of each Scope, and for a period of [***] thereafter,policies of insurance for: (ss) workmen’s compensation in statutory required amounts; (tt) general liability; (uu) automobile liability; and (vv)product21CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYliability, in each case, having policy limits, deductibles and other terms appropriate to the conduct of Fujifilm’s business and sufficient tocover its obligations under this Agreement in Fujifilm’s reasonable judgment and in accordance with any limits and requirements providedby Applicable Laws.b)Sponsor shall secure and maintain in full force and effect throughout the performance of each Scope and for a period of [***] thereafter,policies of insurance for: (ww) general liability; and (xx) product liability, including (if applicable) clinical trial insurance, in each case,having policy limits, deductibles and other terms appropriate to the conduct of Sponsor’s business and sufficient to cover its obligationsunder this Agreement in Sponsor’s reasonable judgment and in accordance with any limits and requirements provided by Applicable Laws.Section 13. DeliveryFujifilm shall package for shipment and deliver all Fujifilm Deliverables or other materials requested to be delivered by Sponsor in writing atSponsor’s expense and in accordance with Sponsor’s written and reasonable instructions with Sponsor bearing all packaging, shipping andinsurance charges. Freight terms shall be Ex Works (Incoterms 2010) Fujifilm Facility. Fujifilm shall retain representative quality retains of Productfor record keeping, testing and regulatory purposes as mutually agreed in the applicable Scope or Quality Agreement and as required by ApplicableLaws. Within [***] following Acceptance of a Batch by Sponsor in accordance with Section 6 of this Agreement, Fujifilm shall notify Sponsor andmake each such Batch available to Sponsor at the Facility. Sponsor shall provide for shipping Product within [***] following notification by Fujifilmthat Fujifilm has made such Batch available. In the event of any delay by Sponsor in shipping one or more shipments of Product in accordancewith this Section 13, the Parties acknowledge and agree that liability and risk of loss for such Batch(es) of Product shall automatically transfer to(and be assumed by) Sponsor effective upon expiration of the [***] period from Batch availability. Upon Sponsor’s request, Fujifilm may storeBatches of Product in accordance with Applicable Laws including cGMP, and Sponsor’s reasonable written instructions for up to an additional [***]without charge to Sponsor. If Sponsor requires a longer period for shipping, Sponsor will notify Fujifilm, and Sponsor will either make arrangementswith a third party for storage on Sponsor’s behalf and at Sponsor’s expense, or Fujifilm and Sponsor may agree to storage terms in a separateTemporary Storage Agreement. If Sponsor requests that Fujifilm carry out stability testing on any such stored Product, if such provision is notalready provided for in the applicable Scope, Fujifilm will conduct such testing in accordance with Applicable Laws and this Agreement, subject tothe Parties’ mutual agreement on terms and conditions therefor to be set forth in a new Scope or, if applicable, a separate Temporary StorageAgreement.Section 14. Default/Limitation of Warrantya)If Fujifilm is in default of its material obligations under this Agreement, Fujifilm shall have a period of [***] from the date of receipt ofnotice of default from Sponsor, within which to cure or, in the case of a default which cannot be cured within [***], to commence todiligently cure such default. If Fujifilm fails to so cure or commence to diligently cure, then this Agreement or the applicable Program shall,at Sponsor’s option, immediately terminate.b)If Sponsor is in default of its material obligations under this Agreement, including payment obligations, Sponsor shall have a period of [***]from the date of receipt of a notice of default from Fujifilm, within which to cure such default, in the case of default which cannot be curedwithin [***] (other than default of payment obligations), to commence to diligently cure such default; provided that if Sponsor fails to socure such breach or commence to diligently cure such breach, within the specified cure period, this Agreement may, at Fujifilm’s option,immediately terminate. For clarity, a Delay shall not constitute a material breach by Sponsor.22CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYc)Disclaimer of Consequential Damages. EXCEPT FOR EACH PARTY’S LIABILITY ARISING OUT OF, RESULTING FROM ORRELATING TO A BREACH OF SECTION 8 (CONFIDENTIAL INFORMATION) OR SECTION 10 (INVENTIONS AND PATENTS) OR ANYOTHER UNAUTHORIZED USE OF THE OTHER PARTY’S INTELLECTUAL PROPERTY OR CONFIDENTIAL INFORMATION, UNDERNO CIRCUMSTANCES SHALL EITHER PARTY BE ENTITLED TO INCIDENTAL, INDIRECT, CONSEQUENTIAL OR SPECIALDAMAGES ARISING IN CONNECTION WITH THIS AGREEMENT OR THE DEFAULT OR BREACH OF ANY OBLIGATION OF THEOTHER PARTY UNDER THIS AGREEMENT (INCLUDING A SCOPE OR ANY DOCUMENTS OR APPENDICES RELATED THERETO),A PRODUCT OR PROGRAM, WHETHER IN CONTRACT, TORT, NEGLIGENCE, STRICT LIABILITY, BY STATUTE OR OTHERWISE,WHICH LIMITATION SHALL APPLY EVEN IF SUCH PARTY HAS BEEN ADVISED OR IS AWARE OF THE POSSIBILITY OF SUCHDAMAGES.d)Liability Cap. EXCEPT FOR: (A) FUJIFILM’S LIABILITY ARISING OUT OF, RESULTING FROM OR RELATING TO A BREACH OFSECTION 8 (CONFIDENTIAL INFORMATION) OR SECTION 10 (INVENTIONS AND PATENTS) OR ANY OTHER UNAUTHORIZEDUSE OF SPONSOR’S INTELLECTUAL PROPERTY OR CONFIDENTIAL INFORMATION; OR [***], FUJIFILM’S MAXIMUM LIABILITYFOR DAMAGES IN CONNECTION WITH A CLAIM RELATED TO THIS AGREEMENT, A PRODUCT, OR PROGRAM, REGARDLESSOF THE CAUSE OF ACTION, WILL NOT EXCEED [***].e)Special Liability Cap. EXCEPT FOR: (A) FUJIFILM’S LIABILITY ARISING OUT OF, RESULTING FROM OR RELATING TO A BREACHOF SECTION 8 (CONFIDENTIAL INFORMATION) OR SECTION 10 (INVENTIONS AND PATENTS) OR ANY OTHER UNAUTHORIZEDUSE OF SPONSOR’S INTELLECTUAL PROPERTY OR CONFIDENTIAL INFORMATION; OR [***], FUJIFILM’S MAXIMUM LIABILITYFOR DAMAGES RELATED TO THIS AGREEMENT, THE PRODUCT OR PROGRAM, REGARDLESS OF THE CAUSE OF ACTION,WILL NOT EXCEED [***].a)Warranty Disclaimer. EXCEPT AS EXPRESSLY STATED IN THIS AGREEMENT (i) NEITHER PARTY PROVIDES TO THE OTHERPARTY HERETO ANY WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT TO THE MATERIALS, PRODUCT, PROGRAM, ANDSERVICES PROVIDED HEREUNDER, AND ALL SUCH WARRANTIES, EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATIONANY IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE ARE WAIVED, AND (ii)FUJIFILM MAKES NO WARRANTIES THAT THE EXECUTION OF THE SCOPE WILL RESULT IN ANY SPECIFIC QUANTITY ORQUALITY OF PRODUCT.b)No claim for liabilities incurred pursuant to the Quality Agreement may be made under the Quality Agreement by any party. Accordingly,performance of the Quality Agreement shall be deemed to be performance under the Scope to which the Quality Agreement relates and assuch any breach of the Quality Agreement shall be deemed to be a breach of the relevant Scope and all liabilities shall be construed andlimited in accordance with this Section 14.Section 15. Dispute Resolutiona)In the event of any Dispute, the senior executives of Sponsor and Fujifilm shall meet as promptly as practicable after receipt of notice ofsuch Dispute to resolve in good faith such Dispute. If Sponsor and Fujifilm are unable to satisfactorily resolve the Dispute within thirty (30)days following referral to the senior executives, then, subject to each Party’s right to seek injunctive relief to protect its rights or for patentor other Intellectual Property matters pursuant to Section 15(e) below, such Dispute shall be finally settled by an arbitrator in accordancewith this Section 15, which arbitration may be initiated by either Party upon written notice to the other Party.23CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYb)The arbitration will be held in New York City, New York. All arbitration proceedings and communications shall be in English.c)The arbitration shall be conducted by the International Chamber of Commerce (“ICC”) in accordance with the Rules of Arbitration of theInternational Chamber of Commerce (“Rules”) by a single neutral arbitrator agreeable to both Parties if the Dispute involves an amount of$1,000,000 or less, and by a panel of three (3) neutral arbitrators if greater than $1,000,000. Each arbitrator shall: (yy) be significantlyexperienced with Delaware law; and (zz) have senior management experience in the biopharmaceutical industry and at least ten (10) yearslegal/judicial experience. If the Parties do not agree on the arbitrator(s) within thirty (30) days of the initiation of the arbitration as indicatedby at least one of the Parties, the ICC shall appoint such arbitrator(s) to hear the case in accordance with the Rules, provided however,that no potential arbitrator shall be appointed unless he or she has agreed in writing to abide and be bound by the provisions in this Section15. The arbitrator(s) shall have no authority to award consequential, punitive or exemplary damages except as provided in this Agreementor to vary from or ignore the terms of this Agreement and shall be bound by controlling law.d)The Parties shall use reasonable efforts to complete any such arbitration (including receiving the final award from such arbitrator(s)) withinsix (6) months from the issuance of notice of a referral of any such Dispute to arbitration. The arbitrator(s) shall determine what discoverywill be permitted, consistent with the goal of limiting the cost and time which the Parties must expend for discovery; provided that thearbitrator(s) shall permit such discovery as he or she deems necessary to permit an equitable resolution of the Dispute.e)Finally, the Parties may seek administrative action or judicial intervention for interim or emergency relief, such as restraining orders andinjunctions where appropriate to protect the rights or Intellectual Property of that Party from the applicable administrative body or a court ofcompetent jurisdiction, as applicable, including pending the selection of the arbitrator(s) or pending the arbitrator’s determination of themerits of any Dispute.f)Any decision by the arbitrator(s) shall, unless clearly erroneous or arbitrary and capricious, be binding upon the Parties with respect to theDispute and may be entered as final judgment in any court having competent jurisdiction. The cost of any arbitration proceeding shall beborne by the Parties, as the arbitrator(s) shall determine if the Parties have not otherwise agreed. The arbitrator(s) shall render their finaldecision in writing to the Parties.g)Fujifilm may suspend performance of any of its obligations hereunder until all undisputed payments are made in accordance with Section5(f).Section 16. Indemnificationa)Subject to and except to the extent of any indemnification from Sponsor pursuant to Section 16(b) below, Fujifilm shall defend, indemnifyand hold harmless Sponsor and its Affiliates and their respective officers, directors and employees (collectively, “Sponsor Group”) fromany loss, cost, damage or expense (“Loss”) incurred by a member of the Sponsor Group from any lawsuit, action, claim, demand,assessment or proceeding brought by a third party (“Claim”) to the extent arising from or related to: (i) negligence, gross negligence orintentional misconduct or inaction of any member of the Fujifilm Group or any third party subcontractors, including Approved Suppliers (butexcluding infringement or misappropriation Claims); (ii) breach of this Agreement by any member of the Fujifilm Group or any third partysubcontractors, including Approved Suppliers; (iii) violation of any Applicable Law with respect to this Agreement by any member of theFujifilm Group or any third party subcontractors, including Approved Suppliers (but excluding infringement or misappropriation Claims); or(iv) claims (A) that Fujifilm Group’s or any third party subcontractors, including Approved Suppliers’ use of Fujifilm’s BackgroundIntellectual Property24CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYor Process Inventions in the performance of a Program infringe or misappropriate the Intellectual Property rights of a third party; or (B) thatFujifilm Group’s or its sublicensee’s use of the Sponsor Process Inventions for any purpose outside of the Program infringe ormisappropriate the Intellectual Property rights of a third party.b)Subject to and except to the extent of any indemnification from Fujifilm pursuant to Section 16(a) above, Sponsor shall defend, indemnifyand hold harmless Fujifilm and its Affiliates and their respective officers, directors and employees (collectively, the “Fujifilm Group”) fromany Loss incurred by a member of the Fujifilm Group as a result of any third party Claim to the extent arising from or related to: (i) the useof Sponsor Materials and the Product (but excluding infringement or misappropriation Claims); (ii) Fujifilm’s proper use of Sponsordesignated Process-Specific Consumables (but excluding infringement or misappropriation Claims); (iii) the negligence, gross negligenceor intentional misconduct or inaction of a member of the Sponsor Group (but excluding infringement or misappropriation Claims); (iv)violation of any Applicable Law by a member of the Sponsor Group with respect to this Agreement (but excluding infringement ormisappropriation Claims); (v) the breach of this Agreement by a member of the Sponsor Group; or (vi) claims that Fujifilm’s use ofSponsor’s Background Intellectual Property, including the Sponsor transferred Product manufacturing process or Sponsor Materials in theperformance of a Program infringe or misappropriate the Intellectual Property rights of a third party; provided however that Fujifilm promptlyceases using such allegedly infringing materials upon Sponsor’s request.c)Upon receipt of notice of any Claim which may give rise to a right of indemnity from the other Party hereto, the Party seekingindemnification (the “Indemnified Party”) shall give written notice thereof to the other Party (the “Indemnifying Party”) with a claim forindemnity. Any delay or failure to give notice shall not discharge the duty of the Indemnifying Party to indemnify except to the extent it isprejudiced by such delay or failure. Such claim for indemnity shall indicate the nature of the Claim and the basis therefore. Promptly aftera Claim is made for which the Indemnified Party seeks indemnity, the Indemnified Party shall permit the Indemnifying Party, at theIndemnifying Party’s option and expense, to assume the complete defense of such Claim, provided that: ([[) the Indemnified Party willhave the right to participate in the defense of any such Claim at its own cost and expense; (aaa) the Indemnifying Party will conduct thedefense of any such Claim in good faith with due regard for the potential related liabilities of the Indemnified Party; (bbb) the IndemnifiedParty shall reasonably cooperate with the Indemnifying Party, in the defense and settlement of such Claim; and (ccc) the IndemnifyingParty will, prior to making any settlement, consult with the Indemnified Party as to the terms of such settlement and receive approvalthereof, such approval not to be unreasonably withheld. The Indemnifying Party will not, in defense of any such Claim, except with theconsent of the Indemnified Party, not to be unreasonably withheld, consent to the entry of any judgment or enter into any settlement whichdoes not include as an unconditional term thereof, the giving by the claimant or plaintiff to the Indemnified Party of a release from allliability in respect thereof. The Indemnifying Party will not have an indemnification obligation with respect to any Claim settled without itsprior written consent. As to those Claims with respect to which the Indemnifying Party does not elect to assume control of the defense,the Indemnified Party will afford the Indemnifying Party an opportunity to participate in such defense at the Indemnifying Party’s own costand expense, and will not settle or otherwise dispose of any of the same without the consent of the Indemnifying Party, not to beunreasonably withheld. For clarity, only Fujifilm and Sponsor will have the right to claim indemnity under this Agreement (on its own behalfor on behalf of the Fujifilm Group and Sponsor Group, respectively), no member of either group shall have the right to directly claim anindemnity hereunder.Section 17. Representations and Warranties25CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYa)Each Party represents and warrants to the other Party that: (ddd) such Party is duly organized, validly existing and in good standing underthe applicable laws of its jurisdiction of incorporation or organization; (eee) it has received all requisite authorization and authority to, andhas the full right and authority to, enter into this Agreement and to perform in accordance with the terms and conditions set forth herein;and (fff) this Agreement has been validly executed and delivered by such Party, and constitutes a valid and binding obligation of suchParty, enforceable against such Party in accordance with its terms except as enforceability may be limited by liquidation, bankruptcy,insolvency, reorganization, moratorium, formal restructuring, or other similar laws relating to or affecting creditors’ rights generally orgeneral principles of equity (regardless of whether enforcement is sought in a proceeding in equity or at law).b)Each Party represents and warrants to the other Party that it has obtained and will at all times during the term of this Agreement, hold andcomply with all licenses, permits and authorizations necessary to perform its obligations under this Agreement as now or hereafterrequired under any Applicable Laws.c)Each Party represents and warrants to the other Party that neither it nor any of its officers, directors, or employees performing servicesunder this Agreement (including the applicable Scope) have been excluded from participation in any government healthcare program,debarred from or under any federal program, or convicted of a crime defined in 42 U.S.C. Section 1320a-7 (or any equivalent legislation ofan individual EU member state or Canada) which could lead to debarment, or otherwise been excluded or deemed ineligible forparticipation in any healthcare programs (collectively, “Debarment”), nor is aware of any pending or potential actions that would give riseto such ineligibility. If at any time the foregoing changes with respect to a Party, such Party shall immediately notify the other Party of thesame in writing, and the notified Party shall have the right to terminate the Scope and/or request the removal of the affected individualsfrom continued performance under the applicable Scope. Fujifilm certifies that it has reviewed applicable U.S. debarment lists (and theequivalent thereof under EU and Canadian laws) with respect to its Subcontractors and has not engaged Subcontractors subject to suchDebarment.d)Fujifilm hereby represents and warrants to Sponsor that: (ggg) Fujifilm is skilled and experienced in performing the Program, and willperform each Program in a professional and workman-like manner consistent with the biopharmaceutical manufacturing industry; (hhh)there is no claim, suit, proceeding, or other investigation pending, or to the actual knowledge of Fujifilm, threatened against Fujifilm, whichis likely to prevent or interfere with Fujifilm’s performance under this Agreement or adversely affect the rights and interests of Sponsorhereunder; (iii) it is under no contractual or other obligation or restriction that is inconsistent with its execution or performance of thisAgreement or the rights granted to Sponsor under this Agreement, and will not enter into any agreement, either written or oral, that wouldconflict with its obligations under this Agreement; and (jjj) to its knowledge, it has not, nor has any of its, officers, shareholders, managers,employees or agents (including Subcontractors), committed any act, made any statement or failed to make any statement that wouldreasonably be expected to provide a basis for the FDA to invoke its policy with respect to “Fraud, Untrue Statements of Material Facts,Bribery, and Illegal Gratuities” set forth in 56 Fed. Reg. 46191 (September 10, 1991), or any other Regulatory Authority to invokesubstantially similar policies, including under any applicable anti-bribery/anti-corruption laws, including the U.K. Anti-Bribery Act.e)Fujifilm represents and warrants to Sponsor that: (i) Fujifilm shall not deliver a Non-Conforming Batch; (ii) without limiting the precedingsentence, Fujifilm will not deliver a Batch which has been adulterated or misbranded by the Fujifilm Group or its Subcontractors within themeaning of Applicable Laws, and (iii) Product will be transferred to Sponsor free and clear of any security interests, lien or encumbrances;provided, however, that the warranties set forth in subsection (i) or (ii) shall not apply in the event Sponsor requests delivery of a Non-Conforming Batch or an adulterated or misbranded Batch.26CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYf)Sponsor hereby represents and warrants to Fujifilm that: (kkk) there is no claim, suit, proceeding, or other investigation pending, or to theactual knowledge of Sponsor, threatened against Sponsor, which is likely to prevent or interfere with Sponsor’s performance under thisAgreement; (lll) it is under no contractual or other obligation or restriction that is inconsistent with its execution or performance of thisAgreement or the rights granted to Fujifilm under this Agreement, and will not enter into any agreement, either written or oral, that wouldconflict with its obligations under this Agreement; and (mmm) to its knowledge, it has not, nor has any of its, officers, shareholders,managers, employees or agents, committed any act, made any statement or failed to make any statement that would reasonably beexpected to provide a basis for the FDA to invoke its policy with respect to “Fraud, Untrue Statements of Material Facts, Bribery, andIllegal Gratuities” set forth in 56 Fed. Reg. 46191 (September 10, 1991), or any other Regulatory Authority to invoke substantially similarpolicies, including under any applicable anti-bribery/anti-corruption laws, including the U.K. Anti-Bribery Act.g)Sponsor hereby represents and warrants to Fujifilm that it has legal title and/or a valid license to the Sponsor Deliverables necessary toconduct the Program in accordance with the applicable Scope and that to Sponsor’s knowledge, Fujifilm’s use of Sponsor’s BackgroundIntellectual Property as contemplated under this Agreement will not violate or infringe on the patents, trademarks, trade names, tradesecrets, service marks or copyrights of any other party.Section 18. Force MajeureEither Party shall be excused from performing its respective obligations under this Agreement to the extent that its performance is delayed orprevented by Force Majeure. The Party subject to such event shall promptly notify the other Party of the occurrence thereof and, if known, theexpected duration. Any time specified or estimated for completion of performance in the Scope falling due during or subsequent to the occurrenceof any or such events shall be automatically extended for a period of time to recover from such disability, provided that the Party suffering suchoccurrence: (a) uses commercially reasonable efforts to mitigate any damages incurred by the other Party, including in the case of Fujifilm, atSponsor’s request, using commercially reasonable efforts to transfer the work performed under a Scope to another Facility, subject to capacityavailability at such other Facilities and, if such Facilities are operated by Affiliates of Fujifilm, execution of an amendment to this Agreementadding such Affiliates to this Agreement; and (b) uses commercially reasonable efforts to resume full performance of its obligations under thisAgreement as soon as reasonably practicable. Fujifilm will promptly notify Sponsor if, by reason of any of the events referred to herein, Fujifilm isunable to meet any such time for performance of a Stage specified in the Scope. If any part of the Program is invalid as a result of such ForceMajeure, Fujifilm will, upon written request from Sponsor, repeat that part of a Program affected by the disability, with such costs and expenses tobe mutually agreed upon in a Change Order. [***].Section 19. DelaysIn the event of any delays to the agreed upon commencement or performance of the Program caused or requested by Sponsor or a Force Majeureaffecting Sponsor, Sponsor will notify Fujifilm in writing as soon as reasonably practicable, including any anticipated impact on the timeline forperformance, and in the event of any delays to the agreed upon commencement or performance of the Program that occur as a result of anyaction or omission of Fujifilm Group or Subcontractors or Force Majeure affecting Fujifilm, Fujifilm will notify Sponsor in writing of the same assoon as reasonably practicable, including any impact on the timeline for performance of the applicable Stage. Any increase in costs or expensesincurred due to any material delays shall be determined in good faith by the Parties via a Change Order. Where such agreed upon Change Orderfor a Delay results in the Manufacturing Stage(s) being performed outside of the original period reserved for such Manufacturing Stage(s) as awhole, and Fujifilm is unable to reallocate resources for use with other clients during the period, then unless otherwise agreed in such ChangeOrder, the cancellation fees set forth in Section 21(f) shall apply.27CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYSection 20. Publicity and Use of NamesThe Parties anticipate opportunities for joint or independent press releases or other announcements relating to the activities contemplated hereby,including any ancillary agreements; provided however, that neither Party may issue any such press release or other announcement relating to theactivities contemplated by this Agreement (including any Scope) or any ancillary matter without the prior written permission of such other Party.The Party wishing to make such release or announcement shall provide a copy of the text thereof to the other Party at least ten (10) businessdays prior to its anticipated release and shall (a) remove any Confidential Information identified by the other Party and (b) in good faith, make anymodifications to address any objections raised by such other Party. After issuance of a press release approved under the preceding sentence,either Party may thereafter make disclosures related to this Agreement consistent with the approved release. For clarity, Fujifilm will not have theright to publish the results of any Program. Without limiting the foregoing, neither Party shall use the name of the other Party, its Affiliates or thenames of the employees of the other Party in any advertising or sales promotional material or in any publication without prior written permission ofsuch other Party. Such consent may not be unreasonably withheld. Each Party shall, however, be entitled to make any disclosures as required inconnection regulatory filings, patent filings, or as otherwise required by Applicable Laws in accordance with Section 8 (Confidential Information) ofthis Agreement.Section 21. Term/Terminationa)Term. This Agreement shall take effect on the Effective Date and continue in effect for a period of ten (10) years or completion of allPrograms, whichever is later. Each Scope shall take effect upon the date of its execution by both Parties and, unless earlier terminated asprovided in this Section 21, continue until the completion of the Program under such Scope. A Program will be deemed completed when allStages defined in the applicable Scope have been completed.b)Termination for Insolvency. Either Party may immediately terminate this Agreement upon written notice to the other Party if: (nnn) theother Party is declared insolvent or bankrupt by a court of competent jurisdiction; (ooo) a voluntary petition in bankruptcy is filed in anycourt of competent jurisdiction by the other Party; or (ppp) this Agreement is assigned by the other Party for the benefit of creditors.c)Termination of a Program Due to Technical Issues. Fujifilm may terminate a Program at any time by giving written notice to Sponsor atleast [***] in advance of such termination, if Fujifilm reasonably believes that it will be unable to carry out and complete such Program inaccordance with the Scope due to discovery of a factor (other than a Fujifilm Fault or Execution Factor) which:(i)Materially and adversely affects the development of the Process; or(ii)Materially and adversely affects, or is likely to materially and adversely affect, production of Product in the Facility; or(iii)Will have an adverse effect on another customer product license or manufacturing license as a result of the Product being introducedinto the Facility,provided that, in each case: (x) such factor was not known and could not reasonably have been known at the commencement of theapplicable Stage of Program; (y) Fujifilm has used commercially reasonable efforts in its attempts to address such factor; and (z) theParties have been unable to agree upon changes to address such factor in a Change Order. Fujifilm acknowledges and agrees thatSponsor has disclosed the use of nickel in the processing of the Product, and such use shall not constitute a factor upon which toexercise this termination right.28CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYd)Termination by Sponsor for Convenience. In addition to the termination rights otherwise set forth in this Agreement, Sponsor may at anytime terminate: (qqq) the entire Agreement; (rrr) individual Program(s), in whole or in part; or (sss) individual Scope, in whole or in part, ineach case, by giving [***] written notice to Fujifilm.e)Payment Due Upon Termination.(i)Upon termination of a Scope under this Agreement by Sponsor pursuant to Section 14(a) (Fujifilm’s uncured default) or Section 21(b)(Fujifilm’s insolvency) or by Fujifilm pursuant to Section 21(c) (Technical Issues), Sponsor shall pay Fujifilm in accordance withSection 5(f), the following amounts for the terminated Scope(s): [***].(ii)In the event Sponsor elects to terminate a Scope pursuant to Section 21(d) (for convenience) or in the event Fujifilm terminatespursuant to Section 14(b) (Sponsor’s uncured default) or Section 21(b) (Sponsor’s insolvency), then, unless otherwise set forth in theapplicable Scope, Sponsor will pay Fujifilm the fees set forth below (with such payment made in accordance with Section 5(f)). [***].(1)all unpaid costs properly incurred or committed for Process Consumables [***](2)with respect to any unbilled amounts set forth in the applicable Payment schedule of the terminated Scope, for all Stages otherthan Manufacturing Stages, on a Stage by Stage basis, [***]; plus(3)With respect to unbilled activities for Manufacturing Stages:(a)If the effective date of termination is on or before the date that is [***] prior to the scheduled commencement date formanufacturing activities, an amount equal to [***] of the unbilled activities for Manufacturing Stages (as amended to includeany executed Change Orders); or(b)If the effective date of termination is after the date that is [***] prior to the scheduled commencement date for manufacturingactivities but on or before the date that is [***] prior to same, an amount equal to [***] of the unbilled activities forManufacturing Stages (as amended to include any executed Change Orders); or(c)If the effective date of termination is after the date that is [***] prior to the scheduled commencement date for manufacturingactivities but on or before the date that is [***] prior to same, an amount equal to [***] of the unbilled activities forManufacturing Stages (as amended to include any executed Change Orders); or(d)If the effective date of termination is after the date that is [***] prior to the scheduled commencement date for manufacturingactivities, an amount equal to [***] of the unbilled activities for Manufacturing Stages (as amended to include any executedChange Orders).a)Fees for Cancellation of Individual Batches. In the event of a Delay under Section 19 for which this Section 21(f) is applicable, or in theevent of a cancellation for reasons other than pursuant to Section 7, Section 14, Section 18, or Section 21(b), of one (1) or more Batches,but not the entire Scope or a Program (for which Section 21(e) above shall apply), Sponsor shall pay Fujifilm, in accordance with Section5(e), the following amounts in respect to the cancelled Batch(es):29CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPY(i)All amounts owed for work properly performed under pre-productions Stages but not yet invoiced; plus(ii)All unpaid costs properly incurred or committed for Process Consumables that are not used [***]; plus(iii)A cancellation fee calculated, unless otherwise set forth in the Scope, as follows:(1)If the effective date of cancellation is on or before the date that is [***] prior to the scheduled commencement date formanufacturing of the cancelled Batch(es), an amount equal to [***] of the unbilled cancelled activities under Manufacturing Stages(as amended to include any executed Change Orders); or(1)If the effective date of cancellation is after the date that is [***] prior to the scheduled commencement date for manufacturingactivities but on or before the date that is four months prior to same, an amount equal to [***] of the unbilled cancelled activitiesto Process such Batch (excluding costs for any Process Consumables); or(2)If the effective date of cancellation is after the date that is [***] prior to the scheduled commencement date for manufacturingactivities but on or before the date that is [***] prior to same, an amount equal to [***] of the unbilled cancelled activities toProcess such Batch (excluding costs for any Process Consumables); or(1)If the effective date of cancellation is after the date that is [***] prior to the scheduled commencement date for manufacturing ofthe cancelled Batch(es), an amount equal to [***] of the cancelled activities to Process such Batch (excluding costs for anyProcess Consumables).Notwithstanding the foregoing, Sponsor shall not be liable to pay to Fujifilm in aggregate a sum in excess of the amount which would havebeen payable had the relevant Batch been manufactured successfully in accordance with the applicable Scope.b)For clarity, in the event Sponsor elects to terminate a Scope, individual Batch, or the Agreement, pursuant to Section 21(d) (forconvenience) or in the event Fujifilm terminates pursuant to Section 14(b) (Sponsor’s uncured default) or Section 21(b) (Sponsor’sinsolvency), then Fujifilm shall have no obligation to refund any pre-paid reservation fees.c)Effects of Termination. The termination of this Agreement for any reason shall relieve neither Party of its obligation to the other forobligations in respect of: (ttt) confidentiality of information; (uuu) consents for advertising purposes and publications; (vvv) indemnification;(www) inventions and patents; (xxx) compensation for services performed; and (yyy) dispute resolution. Further, termination of thisAgreement for any reason shall relieve neither Party of its protections under (x) disclaimer of warranty or (y) limitation of liability.Section 22. Program Managementa)Joint Steering Committee. Upon execution of a Scope under this Agreement, Sponsor and Fujifilm shall establish a Joint SteeringCommittee (the “Joint Steering Committee” or “JSC”) comprised of an equal number of representatives of each Party, which will consistof Program Managers and other functional leaders from areas executing the Program with experience in the development, manufacturing,and commercialization of biologic products and be of the seniority and experience appropriate for participation therein, in light of thefunctions, responsibilities and30CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYauthority of the JSC as further set forth below. Where multiple Programs are agreed under this Agreement, Sponsor and Fujifilm mayagree to establish different Joint Steering Committees for different Products and/or Programs.b)Program Managers. Each Party shall appoint one person to serve as a “Program Manager” under a Scope with responsibility foroverseeing day to day program execution and being the primary point of contact between the Parties with respect to the Program.c)Replacement of Joint Steering Committee Representatives and Program Managers. The Joint Steering Committee may adjustmembership as the Program progresses through various Stages. Each Party shall be free to replace its representative members on theJoint Steering Committee or its Program Manager with new appointees who have authority to act on behalf of such Party, on written noticeto the other Party.d)Responsibilities of Joint Steering Committee. The Joint Steering Committee shall be responsible for overseeing and directing the Parties’interaction and performance of their respective obligations under this Agreement. Without limiting the generality of the foregoing, its dutiesshall include:(i)monitoring the performance of a Program;(ii)resolving disagreements that arise under this Agreement; and(iii)determining the need for, and terms of, any Change Orders.e)Meetings. The Joint Steering Committee shall meet at least once per calendar quarter or as more or less often as otherwise agreed to bythe Parties. In addition, a Party may call a meeting of the JSC upon reasonable notice to the other Party where such meeting isreasonably necessary to monitor Programs and resolve issues arising hereunder and to perform its responsibilities under this Agreement.Such meetings may be in person or by telephone as agreed by the Joint Steering Committee. Each Party shall bear its own travel andlodging expenses related to participation in and attendance at such meetings by its JSC representatives. As required, the Joint SteeringCommittee meetings may include additional relevant function leaders from Sponsor and Fujifilm’s respective teams.f)Minutes. Within [***] after each Joint Steering Committee meeting, a Program Manager shall prepare and distribute minutes of themeeting, which shall summarize in reasonable details the discussion points, actions, and decisions made by the Joint SteeringCommittee. Program Managers from Fujifilm and Sponsor shall alternate preparing meeting minutes, unless the JSC decides otherwise.Minutes shall be approved or disapproved and revised, as necessary, at the next meeting. Final minutes shall be distributed to themembers of the Joint Steering Committee.g)Dispute Resolution. Each Party’s representatives will collectively have one (1) vote. In the event that the Joint Steering Committee cannotreach agreement with respect to any material issue, then the issue shall be resolved in accordance with the dispute resolution provisionsin Section 15.h)Limitations. The Joint Steering Committee is not empowered to amend the terms of this Agreement (including any Scope or the QualityAgreement), cause a Party to make financial commitments or take on additional obligations over its objection, or to expand its scope ofauthority or to determine any issue before the JSC in a manner that would conflict with the express terms and conditions of thisAgreement (including any Scope or the Quality Agreement).Section 23. Assignment31CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYThis Agreement shall not be assigned or transferred in whole or in part by either Party without the prior written consent of the other Party, whichconsent shall not be unreasonably withheld or delayed. Any attempt to assign or transfer this Agreement without such consent shall be void and ofno effect. Notwithstanding the foregoing, without the prior written consent of the other Party, (a) either Party shall be entitled to assign or transferall or part of its rights under this Agreement to a purchaser of all or substantially all of its assets to which this Agreement relates, or an entity withwhich it may merge where it is not the surviving company, provided that in the case of each such assignment or transfer, the assignee agrees inwriting to assume the obligations of the assignor in this Agreement; and (b) in the case of Sponsor, Sponsor shall be entitled to assign or transferits rights under this Agreement without Fujifilm’s consent to any third party licensee or collaborator in connection with the development,manufacturing, and/or commercialization of the Product, provided that (i) the assignee has creditworthiness no less than the creditworthiness ofSponsor, (ii) the assignee is not a contract manufacturer in the biopharmaceutical industry and (iii) the assignee agrees in writing to assume allrelevant obligations undertaken by Sponsor in this Agreement. No assignment shall relieve the assigning Party of responsibility for theperformance of any of its obligations hereunder. The terms of this Agreement shall inure to the benefit of permitted successors and assigns. Forclarity, Fujifilm shall be entitled to subcontract certain obligations in accordance with Section 1(f), and Sponsor shall be entitled to subcontract itsobligations, other than payment obligations, without Fujifilm’s prior written consent. Sponsor shall notify Fujifilm in writing (which may be via e-mail)following any such subcontracting.Section 24. NoticeAll notices to be given under this Agreement shall be in writing and shall be delivered personally, or mailed either by a reputable overnight carrier orfirst class mail, postage prepaid, return receipt requested, to the Parties at the addresses set forth below or such other addresses as the Partiesmay designate in writing. Such notice shall be effective on the date sent, if delivered personally, on the date received as indicated on the courier’sreceipt if sent by overnight carrier, and on the date received as indicated on the return receipt if mailed first class.If to Sponsor: Sesen Bio, Inc.Attn: Chief Financial Officer245 First StreetSuite 1800Cambridge, MA 02142, USA (with a copy to)Sesen Bio, Inc.Attn: Legal Department245 First StreetSuite 1800Cambridge, MA 02142, USAIf to Fujifilm:PresidentFUJIFILM Diosynth Biotechnologies U.S.A., Inc.101 J. Morris Commons LaneMorrisville, NC 27560P: 919-337-4404 (with a copy to)32CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYLegal DepartmentFUJIFILM Holdings America Corporation200 Summit Lake DriveValhalla, New York 10595-1356Section 25. Choice of LawThis Agreement shall be construed and enforced in accordance with the laws of the State of Delaware except for its rules regarding conflict oflaws.Section 26. Waiver/SeverabilityNo waiver of any provision of this Agreement, whether by conduct or otherwise, in any one or more instances shall be deemed to be or beconstrued as a further or continuing waiver of any such provision, or of any other provision or condition of this Agreement, except by an instrumentsigned by the duly authorized representative of the Party making such waiver, which instrument shall make specific reference to this Agreementand shall express the plan or intention to waive the same. If any provisions hereof shall be determined to be invalid or unenforceable, the validityand effect of the other provisions of this Agreement shall not be affected thereby. In such event, the Parties agree to negotiate in good faith anamendment to this Agreement to replace the illegal or unenforceable term in such a way as to, as closely as possible, effect the benefits andburdens for which the Parties have bargained under this Agreement.Section 27. NonsolicitationFor the term of this Agreement, and for [***] following termination of this Agreement, for any reason, neither Sponsor nor Fujifilm nor any of theiremployees or agents shall solicit, hire, or attempt to solicit or hire, any employees of the other who were involved in the Program, unless otherwiseapproved by the other Party; provided that nothing herein shall restrict either Party from soliciting, hiring or attempting to solicit or hire any suchemployees by general employment advertising.Section 28. Entire Agreement; Modification/Counterparts; Constructiona)This instrument including the attached Appendices sets forth the entire agreement between the Parties hereto with respect to theperformance of the Program by Fujifilm for Sponsor and as such, supersedes all prior and contemporaneous negotiations, agreements,representations, understandings, and commitments with respect thereto and shall take precedence over all terms, conditions andprovisions on any purchase order form or form of order acknowledgment or other document purporting to address the same subject matter.In the event of a conflict between the body of this Agreement, the applicable Scope, and the Quality Agreement, the provisions of theQuality Agreement will govern with respect to quality obligations, and the body of this Agreement will control with respect to all othermatters unless the Scope specifically acknowledges the conflict and expressly states the conflicting Scope provision controls. For clarity,this Agreement (i) shall supersede in its entirety, that certain General Contract Terms for Non-GMP Services, dated as of May 11, 2018,between Eleven Biotherapeutics, Inc. and FUJIFILM Diosynth Biotechnologies U.S.A., Inc., with all statements of work entered intothereunder (including Statement of Work #1 dated May 11, 2018 and Statement of Work #2 dated September 7, 2018) governed by thisAgreement and superseding any conflicting language therein as if originally executed under this Agreement, to the extent not prohibited bylaw; and (ii) shall not affect the separate Master Services Agreement currently in place between Sponsor and FDBK, which shall remain ineffect in accordance with its terms. This Agreement shall not be amended, changed, or modified in any manner except by an instrumentsigned by the duly authorized representatives of each of the Parties hereto, which instrument shall make specific reference to thisAgreement and shall express the plan or intention to modify same.33CONFIDENTIAL [***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidentialtreatment has been requested with respect to the omitted portions.FDBU –SESEN MBSA EXECUTION COPYb)This Agreement has been prepared jointly and will not be strictly construed against either Party, and any ambiguities in this Agreement willnot be construed against the other Party, irrespective of which Party may be deemed to have authored the ambiguous provision. Theheadings of each section have been inserted for convenience of reference only and are not intended to limit or expand the meaning of thelanguage contained in any particular section. References to “days” shall mean calendar days unless otherwise specified as a “businessday”. The words “include” or “including” will be construed to mean “including without limitation”, and the word “will” will be construed to havethe same meaning as the word “shall.”c)This Agreement may be executed in one or more counterparts, and delivered by electronic means, including by pdf and/or facsimile, eachof which shall be deemed an original but all of which together shall constitute one and the same instrument.IN WITNESS WHEREOF, the parties hereto have caused this Master Bioprocessing Services Agreement to be duly executed by their authorizedrepresentatives as of the date of the last signature below. Sesen Bio, Inc. FUJIFILM Diosynth Biotechnologies U.S.A., Inc.By: /s/ Tom Cannell By: /s/ M. Meeson Name: Tom Cannell Name: M. Meeson Title: President and CEO Title: President Date: October 4, 2018 Date: October 4, 2018 FUJIFILM Diosynth Biotechnologies U.S.A., Inc.By: /s/ Vincent Romeo Name: Vincent Romeo Title: CFO Date: October 4, 2018 34CONFIDENTIAL SUBSIDIARIES OF THE REGISTRANT Exhibit 21.1SUBSIDIARY JURISDICTION OF INCORPORATIONViventia Bio Inc. Province of Ontario, CanadaViventia Bio USA Inc. Province of Ontario, CanadaViventia Biotech (EU) Limited United KingdomExhibit 23.1Consent of Independent Registered Public Accounting FirmWe consent to the incorporation by reference in the following Registration Statements:(1)Registration Statement (Form S-8 No. 333-195170) pertaining to the Eleven Biotherapeutics, Inc. Amended and Restated 2009 Stock Incentive Plan,2014 Stock Incentive Plan and 2014 Employee Stock Purchase Plan,(2)Registration Statement (Post-Effective Amendment No. 1 to Form S-1 on Form S-3 No. 333-201176) of Eleven Biotherapeutics, Inc.,(3)Registration Statement (Form S-8 No. 333-202677) pertaining to the Eleven Biotherapeutics, Inc. 2014 Stock Incentive Plan,(4)Registration Statement (Form S-8 No. 333-210523) pertaining to the Eleven Biotherapeutics, Inc. 2014 Stock Incentive Plan,(5)Registration Statement (Form S-8 No. 333-217686) pertaining to the Eleven Biotherapeutics, Inc. 2014 Stock Incentive Plan,(6)Registration Statement (Form S-8 No. 333-217687) pertaining to the Eleven Biotherapeutics, Inc. Inducement Stock Option Awards,(7)Registration Statement (Amendment No. 3 to Form S-1 No. 333-220809) of Eleven Biotherapeutics, Inc.,(8)Registration Statement (Form S-3 No. 333-224682) of Eleven Biotherapeutics, Inc.,(9)Registration Statement (Pre-Effective Amendment No. 1 to Form S-3 No. 333-223750) of Eleven Biotherapeutics, Inc., and(10)Registration Statement (Post-Effective Amendment No. 1 to Form S-8 No. 333-224959) pertaining to the Sesen Bio, Inc. 2014 Stock Incentive Plan(formerly known as Eleven Bio, Inc. 2014 Stock Incentive Plan);of our report dated March 1, 2019, with respect to the consolidated financial statements of Sesen Bio, Inc. included in this Annual Report (Form 10-K) ofSesen Bio, Inc. for the year ended December 31, 2018./s/ Ernst & Young LLPBoston, MassachusettsMarch 1, 2019Exhibit 31.1Rule 13a-14(a) CERTIFICATIONI, Thomas R. Cannell, D.V.M., certify that:1.I have reviewed this Annual Report on Form 10-K of Sesen Bio, Inc.;2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to makethe statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered bythis report;3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respectsthe financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;4.The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as definedin Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and15d-15(f)) for the registrant and have:a)Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under oursupervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known tous by others within those entities, particularly during the period in which this report is being prepared;b)Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designedunder our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation offinancial statements for external purposes in accordance with generally accepted accounting principles;c)Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusionsabout the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on suchevaluation; andd)Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’smost recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or isreasonably likely to materially affect, the registrant’s internal control over financial reporting; and5.The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, tothe registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):a)all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting whichare reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; andb)any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’sinternal control over financial reporting. /s/ Thomas R. Cannell Thomas R. CannellPresident and Chief Executive Officer(Principal Executive Officer)Dated: March 1, 2019Exhibit 31.2Rule 13a-14(a) CERTIFICATIONI, Richard F. Fitzgerald, certify that:1.I have reviewed this Annual Report on Form 10-K of Sesen Bio, Inc.;2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to makethe statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered bythis report;3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respectsthe financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;4.The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as definedin Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and15d-15(f)) for the registrant and have:a)Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under oursupervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known tous by others within those entities, particularly during the period in which this report is being prepared;b)Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designedunder our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation offinancial statements for external purposes in accordance with generally accepted accounting principles;c)Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusionsabout the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on suchevaluation; andd)Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’smost recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or isreasonably likely to materially affect, the registrant’s internal control over financial reporting; and5.The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, tothe registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):a)all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting whichare reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; andb)any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’sinternal control over financial reporting./s/ Richard F. Fitzgerald Richard F. FitzgeraldChief Financial Officer(Principal Financial Officer)Dated: March 1, 2019Exhibit 32.1CERTIFICATION PURSUANT TO 18 U.S.C. §1350In connection with the Annual Report on Form 10-K of Sesen Bio, Inc. (the “Company”) for the fiscal year ended December 31, 2018 as filed withthe Securities and Exchange Commission on the date hereof (the “Report”), the undersigned hereby certify, pursuant to 18 U.S.C. Section 1350, that, to thebest of their knowledge:(1)the Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and(2)the information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of theCompany./s/ Thomas R. Cannell Thomas R. CannellPresident and Chief Executive Officer(Principal Executive Officer)Dated: March 1, 2019/s/ Richard F. Fitzgerald Richard F. FitzgeraldChief Financial Officer(Principal Financial Officer)Dated: March 1, 2019

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