Radius Health
Annual Report 2015

Plain-text annual report

RADIUS HEALTH, INC. FORM 10-K (Annual Report) Filed 02/25/16 for the Period Ending 12/31/15 Address Telephone CIK ATTN: CHIEF FINANCIAL OFFICER 950 WINTER STREET WALTHAM, MA 02451 617-551-4000 0001428522 Symbol RDUS SIC Code Industry 2834 - Pharmaceutical Preparations Biotechnology & Drugs Sector Healthcare Fiscal Year 12/31 http://www.edgar-online.com © Copyright 2016, EDGAR Online, Inc. All Rights Reserved. Distribution and use of this document restricted under EDGAR Online, Inc. Terms of Use. Use these links to rapidly review the document TABLE OF CONTENTS INDEX TO CONSOLIDATED FINANCIAL STATEMENTS PART IV Table of ContentsUNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549FORM 10-KCommission file number: 001-35726Radius Health, Inc. (Exact name of registrant as specified in its charter)Delaware (State or other jurisdiction of incorporation or organization) 80-0145732 (I.R.S. Employer Identification No.)950 Winter Street Waltham, Massachusetts (Address of principal executiveoffices) 02451 (Zip Code)617-551-4000 (Registrant's telephone number, including area code) Securities issued pursuant to Section 12(b) of the Act: Common Stock Securities issued pursuant to Section 12(g) of the Act: NoneTitle of each class Name of each exchange on which registeredCommon Stock, par value $0.0001 per share The NASDAQ Global Market Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ý No o Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes o No ý Indicate 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 filing requirementsfor the past 90 days. Yes ý No o Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required tobe submitted and posted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required tosubmit and post such files). Yes ý No o(MarkOne) ý ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACTOF 1934For the fiscal year ended December 31, 2015ORo TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACTOF 1934For the transition period from to  Indicate 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 Form 10-K. o Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See thedefinitions of "large accelerated filer," "accelerated filer" and "smaller reporting company" in Rule 12b-2 of the Exchange Act. (Check one): Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes o No ý The aggregate market value of the registrant's common stock, $0.0001 par value per share ("Common Stock"), held by non-affiliates of the registrant, basedon the last sale price of the Common Stock at the close of business on June 30, 2015 was $2.1 billion. For the purpose of the foregoing calculation only, alldirectors and executive officers of the registrant are assumed to be affiliates of the registrant. Number of shares outstanding of the registrant's common stock, par value $0.0001 per share, as of February 19, 2016: 43,014,243DOCUMENTS INCORPORATED BY REFERENCE Portions of the registrant's definitive proxy statement for its 2016 annual meeting of stockholders are incorporated by reference into Part III of this Form 10-K. Large accelerated filer ý Accelerated filer o Non-accelerated filer o (Do not check if a smaller reporting company) Smaller reporting company oTable of ContentsRadius Health, Inc. Annual Report on Form 10-K For the Fiscal Year Ended December 31, 2015 INDEX Special Note Regarding Forward-Looking Statements 1 Currency and Conversions 2 PART I ITEM 1: Business 3 ITEM 1A: Risk Factors 35 ITEM 1B: Unresolved Staff Comments 63 ITEM 2: Properties 63 ITEM 3: Legal Proceedings 63 ITEM 4: Mine Safety Disclosures 63 PART II ITEM 5: Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of EquitySecurities 64 ITEM 6: Selected Financial Data 66 ITEM 7: Management's Discussion and Analysis of Financial Condition and Results of Operations 68 ITEM 7A: Quantitative and Qualitative Disclosures About Market Risk 88 ITEM 8: Financial Statements and Supplementary Data 89 ITEM 9: Changes in and Disagreements With Accountants on Accounting and Financial Disclosure 120 ITEM 9A: Controls and Procedures 120 ITEM 9B: Other Information 122 PART III ITEM 10: Directors, Executive Officers and Corporate Governance 123 ITEM 11: Executive Compensation 127 ITEM 12: Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 128 ITEM 13: Certain Relationships and Related Transactions, and Director Independence 128 ITEM 14: Principal Accountant Fees and Services 128 PART IV ITEM 15: Exhibits and Financial Statement Schedules 129 Signatures 130 Table of ContentsSPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS This report, including in the sections titled "Risk Factors," "Management's Discussion and Analysis of Financial Condition and Results of Operations" and"Business," contains, in addition to historical information, forward-looking statements. We may, in some cases, use words such as "project," "believe,""anticipate," "plan," "expect," "estimate," "intend," "continue," "should," "would," "could," "potentially," "will," "may" or similar words and expressions thatconvey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements in this Annual Report on Form 10-K mayinclude, among other things, statements about:•the progress of, timing of and amount of expenses associated with our research, development and commercialization activities; •the success of our clinical studies for our investigational product candidates; •our ability to obtain U.S. and foreign regulatory approval for our product candidates and the ability of our investigational product candidates tomeet existing or future regulatory standards; •our expectations regarding federal, state and foreign regulatory requirements; •the therapeutic benefits and effectiveness of our investigational product candidates; •the safety profile and related adverse events of our investigational product candidates; •the timing of and our ability to commercialize abaloparatide following regulatory approval; •our plans with respect to collaborations and licenses related to the development, manufacture or sale of our investigational product candidates; •our expectations as to future financial performance, expense levels and liquidity sources; •our ability to compete with other companies that are or may be developing or selling products that are competitive with our investigational productcandidates; •anticipated trends and challenges in our potential markets; •our ability to attract and motivate key personnel; and •other factors discussed elsewhere in this report. The outcome of the events described in these forward-looking statements is subject to known and unknown risks, uncertainties and other important factorsthat could cause actual results to differ materially from the results anticipated by these forward-looking statements. These important factors include our financialperformance, our ability to attract and retain customers, our development activities and those other factors we discuss in Item 1A of this Annual Report onForm 10-K under the caption "Risk Factors." You should read these factors and the other cautionary statements made in this report as being applicable to allrelated forward-looking statements wherever they appear in this report. These risk factors are not exhaustive and other sections of this report may includeadditional factors which could adversely impact our business and financial performance.1Table of ContentsCURRENCY AND CONVERSIONS In this report, references to "dollar" or "$" are to the legal currency of the United States, and references to "euro" or "€" are to the single currency introducedon January 1, 1999 at the start of the third stage of European Economic and Monetary Union, pursuant to the Treaty establishing the European Communities, asamended by the Treaty on European Union and the Treaty of Amsterdam. Unless otherwise indicated, the financial information in this report has been expressed inU.S. dollars. Unless otherwise stated, the U.S. dollar equivalent information translating euros into U.S. dollars has been made, for convenience purposes, on thebasis of the noon buying rate published by the Board of Governors of the Federal Reserve as of December 31, 2015, which was €1.00 = $1.0859. Such translationsshould not be construed as a representation that the euro has been, could have been or could be converted into U.S. dollars at the rate indicated, any particular rateor at all. Trademarks appearing in this report are the property of their respective holders.2Table of ContentsPART I ITEM 1. BUSINESS. Unless otherwise provided in this report, all references in this report to "we," "us," "our company," "our," or the "Company" refer to Radius Health, Inc.Overview We are a science-driven biopharmaceutical company that is committed to developing innovative therapeutics in the areas of osteoporosis, oncology andendocrine diseases. Our lead product candidate, the investigational drug abaloparatide for subcutaneous injection, has completed Phase 3 development for potentialuse in the reduction of fracture risk in postmenopausal women with osteoporosis and is currently under regulatory review in Europe. Our clinical pipeline alsoincludes an investigational abaloparatide transdermal patch for potential use in osteoporosis and the investigational drug RAD1901 for potential use in hormone-driven, or hormone-resistant, breast cancer, and vasomotor symptoms in postmenopausal women. Our preclinical pipeline includes RAD140, a non-steroidalselective androgen receptor modulator, or SARM, under investigation for potential applications in oncology and multiple conditions where androgen modulationmay offer therapeutic benefit.Our Investigational Product Candidates The following table identifies the investigational product candidates in our current product portfolio, their proposed indication and stage of development:*We submitted an MAA in the European Union for abaloparatide-SC in November 2015, which was validated in December 2015.Abaloparatide Abaloparatide is an investigational therapy for the potential treatment of women with postmenopausal osteoporosis who are at an increased risk for a fracture.Abaloparatide is a novel3Table of Contentssynthetic peptide analog that engages the parathyroid hormone receptor, or PTH1 receptor, and was selected for clinical development based on its favorable bonebuilding activity. Abaloparatide was created to have a unique mechanism of action with the goal of stimulating enhanced bone building activity including boneformation, increasing bone mineral density, restoring bone microarchitecture and augmenting bone strength. We are developing two formulations of abaloparatide:•Abaloparatide-SC— Abaloparatide has completed Phase 3 development for potential use as a daily self-administered injection, which we refer to asabaloparatide-SC. We hold worldwide commercialization rights to abaloparatide-SC, except for Japan. In December 2014, we announced thepositive 18-month top-line data from our Phase 3 ACTIVE clinical trial, in which abaloparatide-SC met the primary endpoint with a statisticallysignificant reduction in new vertebral fractures versus placebo, and in June 2015, we announced the positive top-line data from the first six monthsof the ACTIVExtend clinical trial and the 24-month combined data from ACTIVE and ACTIVExtend. In November 2015, we submitted amarketing authorization application, or MAA, to the European Medicines Agency, or EMA, which was validated and is currently undergoingregulatory review by the EMA. We intend to enter into one or more partnerships or collaborations for the potential commercialization ofabaloparatide-SC prior to a commercial launch. We plan to submit a new drug application, or NDA, in the United States, at the end of the firstquarter of 2016. Subject to regulatory review and a favorable regulatory outcome, we anticipate the first commercial sales of abaloparatide-SC willtake place in 2016. •Abaloparatide-TD— We are also developing abaloparatide-transdermal, which we refer to as abaloparatide-TD, based on 3M's patentedMicrostructured Transdermal System technology for potential use as a short wear-time transdermal patch. We hold worldwide commercializationrights to the abaloparatide-TD technology. During 2014, we reported progress towards the development of an optimized transdermal patch that maybe capable of demonstrating comparability to abaloparatide-SC. In preliminary, nonhuman primate pharmacokinetic studies, we achieved adesirable pharmacokinetic profile, with comparable AUC, Cmax, Tmax and T1/2 relative to abaloparatide-SC. We believe that these results supportcontinued clinical development of abaloparatide-TD toward future global regulatory submissions as a potential post-approval line extension of theinvestigational drug abaloparatide-SC. We commenced a human replicative clinical evaluation of the optimized abaloparatide-TD patch inDecember 2015, with the goal of achieving comparability to abaloparatide-SC. We expect to complete our clinical evaluation of the optimizedabaloparatide-TD patch during 2016.RAD1901 RAD1901 is a selective estrogen receptor down-regulator/degrader, or SERD, that at high doses has potential for use as an oral non-steroidal treatment forhormone-driven, or hormone-resistant, breast cancer. RAD1901 is currently being investigated in postmenopausal women with advanced estrogen receptorpositive, or ER-positive, HER2-negative breast cancer, the most common form of the disease. The compound has the potential for use as a single agent or incombination with other therapies to overcome endocrine resistance in breast cancer. In September 2015, we announced results from a Phase 1 maximum tolerated dose, or MTD, study of RAD1901 in 52 healthy volunteers. In the study,RAD1901 was administered to healthy postmenopausal women in doses ranging from 200mg to 1000mg, and the data showed that RAD1901 was well-toleratedand the overall safety was supportive of continued development. In addition, a subset of subjects that received 18F estradiol positron emission tomography, or FES-PET, imaging demonstrated suppression of the FES-PET signal to background levels after six days of dosing. In December 2014, we commenced a Phase 1, multicenter, open-label, two-part, dose-escalation study of RAD1901 in postmenopausal women with advancedER-positive and HER2-negative breast4Table of Contentscancer in the United States to determine the recommended dose for a Phase 2 clinical trial and to make a preliminary evaluation of the potential anti-tumor effect ofRAD1901. We expect to complete this study by the middle of 2016. Dose escalation is currently ongoing with no dose limiting toxicities to date and we expect toinitiate expansion cohorts in 2016. In December 2015, we commenced a Phase 1 FES-PET study in patients with metastatic breast cancer in the European Union which includes the use of FES-PET imaging to assess estrogen receptor occupancy in tumor lesions following RAD1901 treatment. In July 2015, we announced that early but promising preclinical data showed that our investigational drug RAD1901, in combination with Pfizer's palbociclib,a cyclin-dependent kinase, or CDK, 4/6 inhibitor, or Novartis' everolimus, an mTOR inhibitor, was effective in shrinking tumors. In patient-derived xenograft, orPDx, breast cancer models with either wild type or mutant ESR1, treatment with RAD1901 resulted in marked tumor growth inhibition, and the combination ofRAD1901 with either agent, palbociclib or everolimus, showed anti-tumor activity that was significantly greater than either agent alone. We believe that thispreclinical data suggests that RAD1901 has the potential to overcome endocrine resistance, is well-tolerated, and has a profile that is well suited for use incombination therapy. In January 2016 we entered into a worldwide clinical collaboration with Novartis Pharmaceuticals to evaluate the safety and efficacy of combining RAD1901,with Novartis' investigational agent LEE011 (ribociclib), a CDK 4/6 inhibitor, and BYL719 (alpelisib), an investigational phosphoinositide 3-kinase inhibitor. RAD1901 is also being evaluated at low doses as an estrogen receptor ligand for the potential relief of the frequency and severity of moderate to severe hotflashes in postmenopausal women with vasomotor symptoms. We commenced a Phase 2b clinical study of RAD1901 for the potential treatment of postmenopausalvasomotor symptoms in December 2015.Our Strategy Our goal is to become a leading provider of therapeutics for osteoporosis, cancer and other serious endocrine diseases. To achieve this goal we plan to:•Obtain regulatory approval of abaloparatide-SC and establish sales and marketing capabilities to commercialize abaloparatide-SC in theUnited States. We completed a Phase 3 clinical trial and the first six months of an extension trial of abaloparatide-SC for the potential use in thereduction of fractures in postmenopausal osteoporosis. We submitted an MAA in the European Union for abaloparatide-SC in November 2015,which was validated in December 2015, and plan to submit an NDA for abaloparatide-SC in the United States at the end of the first quarter of 2016. •Selectively pursue partnerships or collaborations to develop and/or commercialize our product candidates. We intend to enter into one ormore partnerships or collaborations for the development or commercialization of our product candidates. We intend to establish one or morepartnerships or collaborations for the potential commercialization of abaloparatide-SC prior to a commercial launch. •Extend the lifecycle of abaloparatide through the continued development of abaloparatide-TD and additional clinical research. We aredeveloping abaloparatide-TD as a short-wear-time transdermal patch and we anticipate, pending successful development and a favorable regulatoryoutcome, commercial launch two to three years after the approval and first commercial sale of abaloparatide-SC. We initiated the clinical evaluationof the optimized abaloparatide-TD patch in December 2015, with the goal of achieving pharmacokinetic equivalence to abaloparatide-SC. Weexpect to complete our clinical evaluation of the optimized abaloparatide-TD patch during5Table of Contents2016. We believe abaloparatide-TD may be submitted for regulatory approval based upon a demonstration of bioequivalence to abaloparatide-SC.Upon completion of clinical evaluation of the optimized abaloparatide-TD patch, we will meet with regulatory agencies to discuss the regulatorypath for the abaloparatide-TD program. If our clinical trials of abaloparatide-SC and abaloparatide-TD are successful, we expect to seek marketingapproval of abaloparatide-TD as a line extension of abaloparatide-SC.We are continuing to evaluate other underserved osteoporosis patient populations that might benefit from abaloparatide therapy. We may engage inadditional clinical research to achieve additional labeling to treat these populations.•Advance the development of RAD1901 for the treatment of breast cancer and vasomotor symptoms. During 2015, we completed a Phase 1MTD study of RAD1901 in healthy volunteers, and commenced Phase 1 studies in patients with metastatic breast cancer in the United States andthe European Union. Preliminary results show that RAD1901 has a favorable safety and tolerability profile and potential anti-tumor effect. Weexpect to initiate expansion cohorts in 2016. In addition, we commenced a Phase 2b study of RAD1901 for the treatment of vasomotor symptoms inDecember 2015. •Continue to expand our product portfolio. We plan to leverage our drug development expertise to discover and develop additionalinvestigational product candidates focused on serious endocrine-related diseases and conditions. We may also consider opportunistically expandingour product portfolio through in-licensing, acquisitions or partnerships.Our OpportunityOsteoporosis Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, which leads to greater fragility and an increase in fracturerisk. All bones become more fragile and susceptible to fracture as the disease progresses. People tend to be unaware that their bones are getting weaker, and aperson with osteoporosis can fracture a bone from even a minor fall. The debilitating effects of osteoporosis have substantial costs. Loss of mobility, admission tonursing homes and dependence on caregivers are all common consequences of osteoporosis. The prevalence of osteoporosis is growing and, according to theNational Osteoporosis Foundation, or NOF, is significantly under-recognized and under-treated in the population. While the aging of the population is a primarydriver of an increase in cases, osteoporosis is also increasing from the use of drugs that induce bone loss, such as chronic use of glucocorticoids and aromataseinhibitors that are increasingly used for breast cancer and hormone therapies used for prostate cancer. The NOF has estimated that 10 million people in the United States, composed of eight million women and two million men, already have osteoporosis, andanother approximately 44 million have low bone mass placing them at increased risk for osteoporosis. In addition, the NOF has estimated that osteoporosis isresponsible for more than two million fractures in the United States each year resulting in an estimated $19 billion in costs annually. The NOF expects that thenumber of fractures in the United States due to osteoporosis will rise to three million by 2025, resulting in an estimated $25.3 billion in costs each year. Worldwide,osteoporosis affects an estimated 200 million women according to the International Osteoporosis Foundation, or IOF, and causes more than 8.9 million fracturesannually, which is equivalent to an osteoporotic fracture occurring approximately every three seconds. The IOF has estimated that 1.6 million hip fractures occurworldwide each year, and by 2050 this number could reach between 4.5 million and 6.3 million. The IOF estimates that in Europe alone, the annual cost ofosteoporotic fractures could surpass €76 billion by 2050.6Table of Contents In 2015, total sales of branded osteoporosis drugs approximated $6.4 billion, worldwide, of which more than $3.0 billion was attributable to injectabletherapies (Source: EvaluatePharma, February 2016, Evaluate Ltd, www.evaluate.com). There are two main types of osteoporosis drugs currently available in theUnited States, anti-resorptive agents and anabolic agents. Anti-resorptive agents act to prevent further bone loss by inhibiting the breakdown of bone, whereasanabolic agents stimulate bone formation to build new bone. We believe there is a large unmet need in the market for osteoporosis treatment because existingtherapies have been reported to have shortcomings in efficacy, tolerability and convenience. For example, one current standard of care, bisphosphonates, which areanti-resorptive agents, has been associated with infrequent but serious adverse events, such as osteonecrosis of the jaw and atypical fractures, especially of longbones. These side effects, although uncommon, reportedly have created increasing concern with physicians and patients. Many physicians are seeking alternativesto bisphosphonates. Lilly's Forteo/Forsteo and Amgen's Prolia are the two primary alternatives to bisphosphonates that are approved for the treatment ofosteoporosis. In 2015, Forteo/Forsteo had reported worldwide sales of approximately $1.3 billion, $0.6 billion in the U.S. and $0.7 billion outside of the U.S., andProlia had reported sales of approximately $1.3 billion, $0.8 billion in the U.S. and $0.5 billion outside of the U.S. Forteo, a 34 amino acid recombinant peptide ofhuman parathyroid hormone, is the only anabolic drug approved in the United States for the treatment of osteoporosis. Today, the treatment of osteoporosis has no clear consensus goals for BMD, bone turnover biomarkers or fracture risk. Patients suffering from osteoporosisare generally treated with a bisphosphonate first, regardless of their initial BMD or fracture risk in order to preserve bone. Those patients that have already sufferedfrom a fracture, lost BMD, or cannot tolerate or comply with bisphosphonate therapies may progress to other therapies such as a RANK-L inhibitor (denosumab) oranabolic therapy (such as teriparatide). Anabolic bone building agents have been reserved primarily for patients with the most severe BMD loss or who fail(i.e. fracture) on prior anti-resportives. The current anti-resorptive treatment paradigm means that the majority of patients only maintain their bone mass withouthaving a sustained benefit in terms of fracture reduction. We believe there is substantive effort underway to update osteoporosis treatment guidelines towards goal directed therapy that could improve outcomes forboth patients and payers. In this new potential goal directed paradigm, patients may be stratified by severity of BMD and fracture risk in order to create anindividualized treatment plan based on achieving a target goal (either BMD or improved 10 year fracture risk reduction). Patients will then be offered therapies thatreduce the near term, higher risk of fracture and then monitored periodically to ensure they remain at goal (i.e. the lowest possible achievable fracture risk score). We believe there is a significant opportunity for anabolic agents that have the potential to provide early, extensive and durable effects on both BMD andfracture risk compared to other approve therapies, with the potential added advantages of convenience and safety. With the addition of new guidelines, expandingresearch, increased diagnosis effort, higher awareness of the long term risk associated with osteoporotic fracture, and new, more effective therapies we believeosteoporosis treatment will expand and thus our potential commercial opportunity.Our Investigational Drug—Abaloparatide Abaloparatide is a novel synthetic peptide analog that engages the PTH1 receptor and was selected for clinical development based on its favorable bonebuilding activity. Parathyroid hormone, or PTH, analogs (like Forteo (teriparatide) and parathyroid hormone-related protein, or PTHrP) represent a family ofproteins and peptides that share regions of partial or complete amino acid sequence similarity. The first 34 amino acids of PTH analogs contain the binding site forengaging the PTH1 receptor. Abaloparatide is a unique 34 amino acid PTH analog that has 41% homology (i.e. amino acid similarity) to Forteo (teriparatide) andhas 76% homology to the first 34 amino acids7Table of Contentsof PTHrP. Abaloparatide is manufactured using organic chemistry techniques to create the 34 amino acid peptide. Abaloparatide was created to have a unique mechanism of action with the goal of stimulating enhanced bone building activity including bone formation,increasing bone mineral density, restoring bone microarchitecture and augmenting bone strength. We believe that abaloparatide is the most advanced PTH analogin clinical development for the treatment of osteoporosis and that, subject to regulatory review and approval, it could have the potential to provide the followingadvantages over other current standard of care treatments for osteoporosis:•improved efficacy—greater bone build at hip and spine with lower vertebral and non-vertebral fracture risk; •earlier onset of building bone; •shorter treatment duration; •no refrigeration of multi-dose injection pen; and •less hypercalcemia. We acquired and maintain exclusive worldwide rights, excluding development and commercialization rights for Japan, to certain patents, data and technicalinformation related to abaloparatide through a license agreement with an affiliate of Ipsen Pharma SAS, or Ipsen. We are developing two formulations of abaloparatide: abaloparatide-SC, an injectable subcutaneous formulation of abaloparatide, and abaloparatide-TD, aline extension of abaloparatide-SC in the form of a convenient, short-wear-time, transdermal patch. We believe that the results from our Phase 3 ACTIVE clinical trial and the first six months of our ACTIVExtend clinical trial, have demonstrated theimproved efficacy of abaloparatide relative to teriparatide (Forteo/Forsteo) in treating osteoporosis, while still maintaining a well-tolerated long-term safety profile.In November 2015, we submitted an MAA in Europe, which was validated in December 2015, and are on track to submit an NDA in the United States, at the endof the first quarter of 2016. During 2014, we reported progress towards the development of an optimized, short-wear-time transdermal patch that may be capable of demonstratingcomparability to abaloparatide-SC injection. In preliminary, nonhuman primate pharmacokinetic studies, we observed a favorable pharmacokinetic profile, withcomparable AUC, Cmax, Tmax and T1/2 relative to abaloparatide-SC. We believe that these results support continued clinical development of abaloparatide-TDtoward future global regulatory submissions as a potential post-approval line extension of the investigational drug abaloparatide-SC. We commenced the clinicalevaluation of the optimized abaloparatide-TD patch at the end of 2015, with the goal of achieving comparability to abaloparatide-SC. If our clinical trials ofabaloparatide-SC and abaloparatide-TD are successful, we expect to seek marketing approval of abaloparatide-TD as a line extension of abaloparatide-SC. Webelieve abaloparatide-TD may be submitted for regulatory approval based upon a demonstration of bioequivalence to abaloparatide-SC. Upon completion ofclinical evaluation of the optimized abaloparatide-TD patch, we will meet with regulatory agencies to discuss the regulatory path for the abaloparatide-TD program.The FDA's approval of abaloparatide-TD, and the timing of any such approval, is dependent upon the approval of abaloparatide-SC.Abaloparatide-SC Phase 3 Clinical Trial In 2014, we completed a multicenter, multinational, double-blind, placebo-controlled Phase 3 clinical trial of abaloparatide-SC, or the ACTIVE trial, in which2,463 postmenopausal women aged 498Table of Contentsto 86 received daily doses of one of the following: 80 µg of abaloparatide, a matching placebo, or the approved dose of 20 µg of Forteo for 18 months. On February 15, 2012, we received a letter from the FDA stating that, after internal consideration, it believes that a minimum of 24-month fracture data arenecessary for approval of new products for the treatment of postmenopausal osteoporosis. We subsequently met with the FDA on March 21, 2012 to discusssatisfying the 24-month data request while preserving the current 18-month primary endpoint. Based upon our discussion with the FDA, we believe that the 18-month primary endpoint will be acceptable, provided that our NDA includes the 24-month fracture data derived from a 6-month extension of the abaloparatide 80µg and placebo groups in our Phase 3 study during which patients received an approved alendronate (generic Fosamax) therapy for osteoporosis management.Accordingly, patients from the abaloparatide-SC and placebo groups from our ACTIVE trial were eligible to continue in an extension study, or the ACTIVExtendtrial, in which they received 70 mg once weekly of an approved alendronate therapy for osteoporosis management. We intend to submit the NDA with the 24-month fracture data at the end of the first quarter of 2016. The ACTIVE trial was designed to evaluate as the primary endpoint whether abaloparatide-SC is superior to placebo for prevention of vertebral fracture. Thetop-line results of the 18-month ACTIVE trial showed that abaloparatide-SC met the primary endpoint with a statistically significant 86% reduction in newvertebral fractures versus placebo, and Forteo met the same endpoint with a statistically significant 80% reduction. On the secondary endpoints, as compared toplacebo, abaloparatide achieved a statistically significant reduction of 43% in non-vertebral fracture; a statistically significant reduction of 43% in the clinicalfracture; and a significant difference in the time to first incident of non-vertebral fracture and clinical fracture. An exploratory analysis of the ACTIVE trial showed that, for major osteoporotic fractures, there was a statistically significant 70% reduction in majorosteoporotic fractures for the abaloparatide treatment group versus placebo, and a statistically significant 55% reduction in major osteoporotic fractures for theabaloparatide-SC treatment group as compared to Forteo over the 18-month period. The results from the first six months of the ACTIVExtend study showed that the group previously treated with abaloparatide-SC had no new vertebralfractures during the first six months of receiving alendronate. From the start of the ACTIVE trial, this group showed a statistically significant 87% reduction in newvertebral fractures, a 52% reduction in non-vertebral fractures, a 45% reduction in clinical fractures and a 58% reduction in major osteoporotic fractures over the24-month period, as compared to placebo.Abaloparatide-SC Phase 2 Clinical Trial In 2009, we completed a randomized, placebo-controlled, parallel group dose-finding Phase 2 study in the United States, Argentina, India and the UnitedKingdom. Data from our Phase 2 study showed abaloparatide produced faster and greater BMD increases at the spine and the hip after six months and 12 months oftreatment than did Forteo, which was a comparator in our study. Key findings were that the highest dose of abaloparatide tested of 80 µg increased mean lumbarspine BMD at six months and 12 months by 6.7% and 12.9% compared to the increases seen with Forteo trial arms of 5.5% and 8.6%, respectively. Abaloparatidealso produced increases in mean femoral neck BMD at the hip at six months and 12 months of 3.1% and 4.1% compared to increases for Forteo of 1.1% and 2.2%,respectively. Abaloparatide was generally safe and well tolerated in this study, with adverse events similar between abaloparatide, placebo and Forteo groups. Inaddition, the occurrence of hypercalcemia as a side effect for the 80 µg dose of abaloparatide was half that seen with Forteo.Abaloparatide-SC Phase 1 Clinical Trials We have completed seven Phase 1 clinical trials of abaloparatide-SC. Together with our Phase 2 and Phase 3 clinical trials, over 1,500 patients have receivedany dose/route of abaloparatide. The results of our Phase 1 clinical trials suggest that abaloparatide-SC is safe and well tolerated at doses of up to 240 m gadministered once daily.9Table of ContentsAbaloparatide-TD Phase 2 Clinical Trial In 2013, we completed a randomized, double-blind, placebo-controlled, Phase 2 clinical trial of abaloparatide administered via a coated transdermalmicroarray delivery system in healthy postmenopausal women with osteoporosis. This study was conducted in nine centers in the United States, Denmark, Polandand Estonia. The primary objective of this study was to determine the clinical safety and efficacy of abaloparatide-TD as assessed by changes in BMD whencompared to a transdermal placebo and abaloparatide-SC. The results showed that for each abaloparatide-TD dose there was a statistically significant mean percentincrease from baseline in BMD at the lumbar spine, as compared to placebo. For the 100 µg and 150 µg abaloparatide-TD doses, there was also a statisticallysignificant mean percent increase from baseline in BMD at the hip, as compared to placebo. The highest abaloparatide-TD dose of 150 µ g produced increases inBMD from baseline in the lumbar spine and total hip of +2.9% and +1.5%, respectively, compared to changes in the placebo group of +0.04% and –0.02%,respectively. In addition, there was a consistent dose effect seen with increasing doses of abaloparatide-TD, with a statistically significant dosing trend seen forchanges in both spine and total hip BMD. Further, the overall tolerability and safety profile was acceptable; there were no clinically significant signs of anti-abaloparatide antibodies; and patient ratings of patch adhesion and local skin response to the transdermal patch technology were also acceptable.Abaloparatide-TD Phase 1 Clinical Trials We have completed three Phase 1 clinical trials that collectively evaluated the safety, PK, time course of delivery and dose ranging of abaloparatide-TD.Abaloparatide-TD was characterized by a rapid release of abaloparatide with a faster time to reach peak concentration as well as more rapid elimination in plasmacompared to abaloparatide-SC. Peak transdermal drug levels were consistent with abaloparatide-SC. An optimal wear time of five minutes or less was identified aswell as effective sites of application. Abaloparatide-TD showed an increase in the bone-formation marker P1NP in serum after seven days of exposure, consistentwith bone-building activity, and was shown to be safe and well tolerated in all doses studied.Preclinical Pharmacology of Abaloparatide We have completed several preclinical studies of abaloparatide, and we observed the following:•abaloparatide was a potent selective agonist of the human PTH type 1 receptor (PTHR1), with binding selectivity for the RG vs R0 receptorconformation compared to PTH(1-34) and greater selectivity than PTHrP(1-34); •in models of calcium mobilization, abaloparatide has significantly less calcium mobilizing activity at higher doses than PTHrP(1-34), and lessactivity than PTH(1-34); •abaloparatide-SC stimulated the formation of normal, well-organized bone and restored BMD in ovariectomized, or OVX, osteopenic rats andprimates; mechanical testing of bones from OVX rats after treatment with abaloparatide-SC revealed a significant increase in femur and vertebralbone strength; similar studies in rats with abaloparatide-TD showed comparable restoration of bone; •abaloparatide-SC was generally well tolerated over a wide range of doses in two species, rats and primates, for up to six months and nine months,respectively; and •safety pharmacology studies showed no respiratory, gastroenterologic, hematologic, renal or central nervous system effects. A two-year subcutaneous injection carcinogenicity study of abaloparatide in Fischer 344 albino rats was conducted to assess the carcinogenic potential ofabaloparatide. The study was conducted according10Table of Contentsto the provisions set forth in Guidance ICH-S1A, ICH-S1B and ICH-S1C(R2), and the design was accepted under a Special Protocol Assessment by the FDA onJuly 15, 2009. This study evaluated three abaloparatide dose levels. The doses were selected based upon findings and tolerance in completed long-term rattoxicology studies and the anticipated tolerance over a two-year dosing period. Furthermore, the doses represent an exposure multiple over maximum clinicaldoses. The study included a cohort of rats being dosed with a daily subcutaneous injection of PTH(1-34) as a positive control, as it was anticipated thatosteosarcomas would be observed with this treatment, as previously published for both rhPTH(1-34) and rhPTH(1-84) in similar two-year rat carcinogenicitystudies. The positive control served to provide confirmation of the sensitivity of the model. The results of the study revealed osteosarcomas in our carcinogenicitystudy in both the abaloparatide and PTH(1-34) treated groups, with similar frequency between abaloparatide and PTH(1-34) when comparing comparable exposuremultiples to the human therapeutic dose. We have also conducted one preclinical bone quality study in OVX rats with 12 months of daily abaloparatide-SC dosing and a second preclinical bone qualitystudy in adult OVX monkeys for 16 months. The primary objective of these studies was to determine the long-term treatment effects of abaloparatide-SC on bonequality. Effects on bone mass, both cortical bone and cancellous bone, were assessed by BMD and peripheral quantitative CT, and bone strength was determined bybiomechanical testing. The mechanisms by which abaloparatide affects bone were assessed by evaluation of biomarkers of bone turnover and histomorphometricindices of bone turnover. Data from the 12-month rat study showed marked, dose dependent increases in BMD following abaloparatide treatment, increases in boneformation markers, but not bone resorption, and an increase in bone strength. Results from the 16-month monkey OVX study have also shown significant BMD gains, together with increases in bone strength.Breast Cancer According to the World Health Organization, breast cancer is the second most common cancer in the world and the most prevalent cancer in women,accounting for 16% of all female cancers. The major cause of death from breast cancer is metastases, most commonly to the bone, liver, lung and brain.Approximately 30% of early-stage patients develop metastatic disease, and of those patients 90% relapse between therapy levels. About 5% of patients have distantmetastases at the time of diagnoses, and these patients have a five-year survival rate of only 25%, compared with a greater than 99% survival rate for patients withonly local disease. Importantly, even patients without metastases at diagnosis are at risk for developing metastases over time. Approximately 70% of breast cancers express the ER and depend on estrogen signaling for growth and survival. Patients with ER-positive breast cancers aretypically treated with endocrine therapies. There are three main classes of therapies for ER-positive tumors available: aromatase inhibitors, or AIs; selectiveestrogen receptor modulators, or SERMs; and selective estrogen receptor degraders, or SERDs. AIs, which block the generation of estrogen, and SERMs, whichselectively inhibit an ER's ability to bind estrogen, both block ER-dependent signaling but leave functional ERs present on breast cancer cells. For this reason,although AIs and SERMs are effective treatments for some breast cancers, some patients often acquire resistance to them by developing the ability to signalthrough the ER in a ligand-independent manner. In contrast, SERDs are a class of endocrine therapies that directly induce ER degradation. Therefore, SERDsshould have the potential to treat ER-dependent tumors without allowing ligand-independent resistance to develop, and to act on AI- and SERM-resistant ER-positive tumors. Currently only one SERD, fulvestrant, is approved for the treatment of ER-positive metastatic breast cancer. We believe a significant opportunity exists fornew oral therapies that do not allow ligand-independent resistance to develop and can more effectively treat ER-positive breast cancer.11Table of ContentsOur Investigational Drug—RAD1901 RAD1901 is a SERD that at high doses has potential for use as an oral non-steroidal treatment for hormone-driven, or hormone-resistant, breast cancer.RAD1901 is currently being investigated in postmenopausal women with advanced ER-positive, HER2-negative breast cancer, the most common form of thedisease. The compound has the potential for use as a single agent or in combination with other therapies to overcome endocrine resistance in breast cancer.RAD1901 selectively binds to and degrades the estrogen receptor. In preclinical models of ER-positive breast cancer, RAD1901 has shown potent anti-tumoractivity and complete degradation of the ER and progesterone receptor, an ER-regulated gene. RAD1901 has shown good tissue selectivity in preclinical modelsand does not appear to stimulate the uterine endometrium while it appears to protect against bone loss in an ovariectomy-induced osteopenia rat model. WhenRAD1901 was used in combination with other approved breast cancer agents such as everolimus, an mTOR inhibitor, or the inhibitor palobciclib, a CDK 4/6inhibitor, greater tumor shrinkage in PDx animal models was achieved than with the agents alone. In addition, RAD1901 has been shown to effectively inhibittumor growth in PDx models that harbor mutations in the ER, a potential mechanism of endocrine therapy resistance. In a healthy volunteer study, FES-PETimaging was used to assess how much RAD1901 has engaged in the ER, RAD1901 showed suppression of the FES-PET signal to background levels after six daysof dosing. Studies with RAD1901 have established the PK profile, including demonstration of good oral bioavailability. We believe that, subject to successfuldevelopment, regulatory review and approval, RAD1901 could have the potential to offer the following advantages over other current standard of care treatmentsfor ER-positive breast cancer:•ability to suppress estrogen receptor turnover; •favorable tolerability profile; •oral administration; and •treatment of hormone-resistant breast cancers. We exclusively licensed the worldwide rights to RAD1901 from Eisai Co. Ltd., or Eisai.Phase 1 Studies—Breast Cancer In September 2015, we announced results from a Phase 1 maximum tolerated dose, or MTD, study of RAD1901 in 52 healthy volunteers. In the study,RAD1901 was administered to healthy postmenopausal women in doses ranging from 200mg to 1000mg, and the data showed that RAD1901 was well-toleratedand the overall safety was supportive of continued development. In addition, a subset of subjects that received 18F estradiol positron emission tomography, or FES-PET, imaging demonstrated suppression of the FES-PET signal to background levels after six days of dosing. In December 2014, we commenced a Phase 1, multicenter, open-label, two-part, dose-escalation study of RAD1901 in postmenopausal women with advancedER-positive and HER2-negative breast cancer in the United States to determine the recommended dose for Phase 2 studies and to make a preliminary evaluation ofthe potential anti-tumor effect of RAD1901. We expect to complete this study by the middle of 2016. Dose escalation is currently ongoing with no dose limitingtoxicities to date, and we expect to initiate expansion cohorts in 2016. In December 2015, we commenced a Phase 1 FES-PET study in patients with metastatic breast cancer in the European Union which includes the use of FES-PET imaging to assess estrogen receptor occupancy in tumor lesions following RAD1901 treatment. In January 2016 we entered into a worldwide clinical collaboration with Novartis Pharmaceuticals to evaluate the safety and efficacy of combining RAD1901,with investigational agent LEE01112Table of Contents(ribociclib), a CDK 4/6 inhibitor and BYL719 (alpelisib), an investigational phosphoinositide 3-kinase inhibitor.Preclinical Pharmacology of RAD1901 RAD1901 has been shown to bind with good selectivity to the ER alpha, or ER a , and to have both estrogen-like and estrogen antagonist effects in differenttissues. RAD1901 has also been shown to have estrogen-like behavioral effects in an animal model of partner preference and to reduce vasomotor signs in ananimal model of menopausal hot flashes. In bone, RAD1901 protected against gonadectomy-induced bone loss. RAD1901 does not stimulate the endometrium, asshown in short- and long-term animal models, where changes in uterine weight, uterine epithelial thickness, and C3 gene expression are measured, all of which aresensitive indicators. In studies in which an estrogen is used to stimulate the endometrium, RAD1901 antagonizes this estrogen-mediated stimulation of theendometrium. In cell culture, RAD1901 does not stimulate replication of breast cancer cells, and antagonizes the stimulating effects of estrogen on cellproliferation. Furthermore, in breast cancer cell lines a dose dependent down regulation of ER a is observed, a process we have shown to involve proteosomal-mediated degradation pathway. In a model of breast cancer, in which human breast cancer cells are implanted in mice and allowed to establish tumors in responseto estrogen treatment, we observed that treatment with RAD1901 results in decreased tumor growth. In July 2015, we announced that early but promising preclinical data show that our investigational drug RAD1901, in combination with Pfizer's palbociclib, aCDK 4/6 inhibitor, or Novartis' everolimus, an mTOR inhibitor, was effective in shrinking tumors. In PDx breast cancer models with either wild type or mutantESR1, treatment with RAD1901 resulted in marked tumor growth inhibition, and the combination of RAD1901 with either agent, palbociclib or everolimus,showed anti-tumor activity that was significantly greater than either agent alone.Our Investigational Drug—RAD140 RAD140 is a potent, orally bioavailable non-steroidal SARM that resulted from an internal drug discovery program focused on the androgen receptorpathway, which is highly expressed in many ER-positive and ER-negative breast cancers. Due to its receptor and tissue selectivity, potent oral activity and longduration half-life, RAD140 could have clinical potential in the treatment of oncology and multiple conditions where androgen modulation may offer therapeuticbenefit.Vasomotor symptoms Vasomotor symptoms, such as hot flashes, hot flushes and night sweats, are common during menopause, with up to 85% of women experiencing them duringthe menopause transition, for a median duration of four years. An estimated two million women go through menopause every year in the United States, with a totalpopulation of 45 million postmenopausal women. In addition, most women receiving systemic therapy for breast cancer suffer hot flashes, often with more severeor prolonged symptoms than women experiencing natural menopause. These symptoms can disrupt sleep and interfere with quality of life. Historically hormone replacement therapy, or HRT, with estrogen and/or progesterone has been considered the most efficacious approach to relievingmenopausal symptoms such as hot flashes. However, data from the Women's Health Initiative, or WHI, identified increased risks for malignancy andcardiovascular disease associated with estrogen therapy. Sales of HRT declined substantially after the release of the initial WHI data, but HRT remains the currentstandard of care for many women suffering from hot flashes. However, due to concerns about the potential long-term risks and contraindications associated withHRT, we believe that there is a significant need for new therapeutic options to treat vasomotor symptoms.13Table of ContentsOur Investigational Drug—RAD1901 RAD1901 is also being evaluated at low doses as an estrogen receptor ligand for the potential relief of the frequency and severity of moderate to severe hotflashes in postmenopausal women with vasomotor symptoms. We believe that the studies completed to date have demonstrated RAD1901's acceptable safetyprofile and potential to reduce or prevent hot flashes associated with menopause, while simultaneously providing a bone-protective effect, without stimulatingbreast or uterine tissues. We commenced a Phase 2b clinical study of RAD1901 for the potential treatment of postmenopausal vasomotor symptoms in December 2015. We plan toenroll 300 healthy postmenopausal women between the ages of 40 and 65 years old with moderate to severe hot flashes in approximately sixty clinical sites acrossthe United States.Phase 2 Study—Vasomotor Symptoms A Phase 2 proof-of-concept study was conducted in 100 healthy perimenopausal women using four doses of RAD1901 (10 mg, 25 mg, 50 mg and 100 mg)and placebo. The primary study outcome was reduction in the frequency and severity of moderate and severe hot flashes. While a classic dose-response effect wasnot demonstrated, efficacy was determined to occur at the 10 mg dose level which achieved a statistically significant reduction in the frequency of moderate andsevere hot flashes both by linear trend test and by comparison to placebo and in overall (mild-moderate-severe) hot flashes at either the two-, three- or four-weektime-points. A similar reduction in composite score (frequency × severity of hot flashes) was identified at all time-points, with a statistically significant differencefrom placebo achieved at the two-, three- or four-week time-points. Numerical reductions in mean severity and mean daily severity were observed, but did notreach statistical significance. We believe RAD1901 is an attractive candidate for advancement to Phase 3 development as a potential treatment for vasomotorsymptoms. No serious adverse events, or SAEs, were reported during the course of the study. Overall, 69% of patients had an adverse event, generally mild or moderatein severity, with some evidence of dose dependency, and events were most commonly gastrointestinal symptoms and headaches. Three severe adverse eventsoccurred, one in a placebo patient, none of which were considered treatment related. Two patients discontinued treatment due to an adverse event, neither inrelation to the 10 mg dose.Phase 1 Study—Vasomotor Symptoms We have conducted Phase 1 safety, PK and bioavailability studies of RAD1901 in 80 healthy postmenopausal women over a range of doses. Bioavailabilitywas determined to be approximately 10%. Food effect was also investigated and the presence of food was determined to increase absorption and delay clearance ofRAD1901. RAD1901 was generally well tolerated at all dose levels tested. All study-related adverse events were of mild intensity, with some increase in frequencyat the higher doses in the multiple dose group, most commonly gastrointestinal symptoms and headaches. There were no SAEs observed.Manufacturing We do not own or operate manufacturing facilities for the production of any of our investigational product candidates, nor do we have plans to develop ourown manufacturing operations in the foreseeable future. The active pharmaceutical ingredient, or API, of abaloparatide is manufactured on a contract basis byLonza Group Ltd., or Lonza, using a solid phase peptide synthesis assembly process, and purification by high pressure liquid chromatography. Abaloparatide-SC issupplied as a liquid in a multi-dose cartridge for use in a pen delivery device. The pen delivery device is manufactured by Ypsomed AG. The multi-dose cartridgesand pen delivery device are filled, assembled and packaged by Vetter Pharma Fertigung GmbH & Co. Abaloparatide-TD is manufactured by 3M based on their14Table of Contentspatented microneedle technology to administer drugs through the skin, as an alternative to subcutaneous injection. The API of RAD1901 is manufactured for us ona contract basis by Patheon, Inc. Manufacturing is subject to extensive regulations that impose various procedural and documentation requirements, which govern record keeping,manufacturing processes and controls, personnel, quality control and quality assurance, among others. Our contract manufacturing organizations are required tomanufacture our investigational product candidates under current Good Manufacturing Practice, or cGMP, conditions. cGMP is a regulatory standard for theproduction of human pharmaceuticals that imposes extensive procedural, substantive and record keeping requirements on the manufacturing process and associatedproduction and testing facilities.Intellectual Property As of December 31, 2015, we owned or co-owned 11 issued U.S. patents, as well as 29 pending U.S. patent applications and about 39 pending foreign patentapplications in Europe and 15 other jurisdictions, and about 22 granted foreign patents. As of December 31, 2015, we had licenses to 8 U.S. patents related tocompositions and related uses thereof as well as numerous foreign counterparts to many of these patents and patent applications. We strive to protect the proprietary technology that we believe is important to our business, including seeking and maintaining patents intended to cover ourinvestigational product candidates and compositions, their methods of use and processes for their manufacture and any other inventions that are commerciallyimportant to the development of our business. We also rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not considerappropriate for, patent protection. Our success will significantly depend on our ability to obtain and maintain patent and other proprietary protection for commercially important technology andinventions and know-how related to our business, defend and enforce our patents, preserve the confidentiality of our trade secrets, and operate without infringingthe valid and enforceable patents and proprietary rights of third parties. We also rely on know-how and continuing technological innovation to develop andmaintain our proprietary position.Abaloparatide We acquired and maintain exclusive worldwide rights, excluding development and commercialization rights for Japan, to certain patents, data and technicalinformation related to abaloparatide through a license agreement with an affiliate of Ipsen. Composition of matter of abaloparatide is claimed in the United States(U.S. Patent No. 5,969,095), Europe, Australia, Canada, China, Hong Kong, South Korea, New Zealand, Poland, Russia, Singapore, Mexico, Hungary, and Taiwan.These patents have a statutory expiration date of 2016. European Patent No. 0847278, which was included in the license from Ipsen and claimed the composition ofmatter of abaloparatide, lapsed due to Ipsen's failure to pay annuities. We are pursuing restoration of those patent rights. To date, the patent rights in Austria,Belgium, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Sweden, and the United Kingdom have been restored. We believethat the data and market exclusivity provided in Europe for a new chemical entity, coupled with the need for a potential competitor to conduct clinical trials willlikely provide a longer barrier to entry than the patent protection provided by the original European patent term, which will expire in 2016. The Phase 3 clinicaldosage of abaloparatide by the subcutaneous route for potential use in treating osteoporosis is covered by Patent No. 7,803,770 until the statutory term expiresOctober 3, 2027 which we expect will be extended to March 26, 2028 (statutory term extended with 175 days of patent term adjustment due to delays in patentprosecution by the United States Patent and Trademark Office, or USPTO) in the15Table of ContentsUnited States (not including any patent term extension under the Hatch-Waxman Act). The intended therapeutic formulation for abaloparatide-SC is covered byPatent No. 8,148,333 until 2027 in the United States (not including any patent term extension under the Hatch-Waxman Act). Related patents granted in Australia,China, Israel, Japan, South Korea, Mexico, New Zealand, Russia, Singapore, and Ukraine, and currently pending in Brazil, Canada, Europe, Hong Kong, India,South Korea, Norway, and Singapore, will have a patent expiration date of 2027, not taking into account extension under any applicable laws. Patent applicationswhich cover various aspects of abaloparatide for microneedle application are pending in the United States, Australia, Brazil, Canada, China, Europe, Hong Kong,Israel, India, Japan, South Korea, Mexico, New Zealand, Russia, Singapore, and Ukraine. Any patents that might issue from these applications will have a statutoryexpiration date in 2032, not taking into account extension under any applicable laws.RAD1901 We exclusively licensed the worldwide rights to RAD1901 from Eisai. US Patent No. 7,612,114 (statutory term expires December 25, 2023 which we expectwill be extended up to August 18, 2026 with 967 days of patent term adjustment not taking into account any Hatch-Waxman patent term extensions) coversRAD1901 as a composition of matter as well as the use of RAD1901 for treatment of estrogen-dependent osteoporosis or estrogen-dependent breast cancer.Corresponding patents issued in Australia, Canada and Europe and pending in India will have a statutory expiration date in 2023, not taking into account extensionunder any applicable laws. Patent applications covering methods of using RAD1901 for the treatment of vasomotor symptoms are issued in the United States (USPatent No. 8,933,130, statutory term expires June 22, 2027, which we expect will be extended up to October 19, 2031 with 1,580 days of patent term adjustmentnot taking into account any Hatch-Waxman patent term extensions), Canada and Europe; any issued patents will have a statutory expiration date in 2027. Patentapplications covering a dosage form have been filed in the United States, Europe, Canada and Mexico, and any claims that might issue from these applications willhave a statutory expiration date in 2031.RAD140 The composition of matter of, and methods of using, RAD140 are covered by US Patent No. 8,067,448 (statutory term expires February 19, 2029, which weexpect will be extended to September 25, 2029, with 218 days of patent term adjustment due to delays by the USPTO, not taking into account any Hatch Waxmanpatent term extensions) and U.S. Patent No. 8,268,872 (statutory term expires February 19, 2029 which we expect will be extended to September 25, 2029 withpatent term adjustment, subject to a terminal disclaimer of Patent Nos. 8,067,448 and 8,455,525). Related patents have been granted in Australia, Canada, Europe,Japan and Mexico and additional patent applications are pending in Brazil and India. Any patents issued from these filings will have a statutory expiration date in2029. There can be no assurance that an issued patent will remain valid and enforceable in a court of law through the entire patent term. Should the validity of apatent be challenged, the legal process associated with defending the patent can be costly and time consuming. Issued patents can be subject to oppositions,interferences and other third-party challenges that can result in the revocation of the patent or that can limit patent claims such that patent coverage lacks sufficientbreadth to protect subject matter that is commercially relevant. Competitors may be able to circumvent our patents. Development and commercialization ofpharmaceutical products can be subject to substantial delays and it is possible that at the time of commercialization any patent covering the product has expired orwill be in force for only a short period of time following commercialization. We cannot predict with any certainty if any third party U.S. or foreign patent rights, orother proprietary rights, will be deemed infringed by the use of our technology. Nor can we predict with certainty which, if any, of these rights16Table of Contentswill or may be asserted against us by third-parties. Should we need to defend ourselves and our partners against any such claims, substantial costs may be incurred.Furthermore, parties making such claims may be able to obtain injunctive or other equitable relief, which could effectively block our ability to develop orcommercialize some or all of our products in the United States and abroad, and could result in the award of substantial damages. In the event of a claim ofinfringement, we or our partners may be required to obtain one or more licenses from a third party. There can be no assurance that we can obtain a license on areasonable basis should we deem it necessary to obtain rights to an alternative technology that meets our needs. The failure to obtain a license may have a materialadverse effect on our business, results of operations and financial condition. We also rely on trade secret protection for our confidential and proprietary information. No assurance can be given that we can meaningfully protect our tradesecrets on a continuing basis. Others may independently develop substantially equivalent confidential and proprietary information or otherwise gain access to ourtrade secrets. It is our policy to require our employees and consultants, outside scientific collaborators, sponsored researchers and other advisors who receive confidentialinformation from us to execute confidentiality agreements upon the commencement of employment or consulting relationships. These agreements provide that allconfidential information developed or made known to these individuals during the course of the individual's relationship with us is to be kept confidential and is notto be disclosed to third parties except in specific circumstances. The agreements provide that all inventions conceived by an employee shall be our property. Therecan be no assurance, however, that these agreements will provide meaningful protection or adequate remedies for our trade secrets in the event of unauthorized useor disclosure of such information. Our success will depend in part on our ability to obtain and maintain patent protection, preserve trade secrets, prevent third parties from infringing upon ourproprietary rights and operate without infringing upon the proprietary rights of others, both in the United States and other territories worldwide.Competition The development and commercialization of new products to treat the targeted indications of our investigational product candidates is highly competitive, andour products, if approved, will face considerable competition from major pharmaceutical, biotechnology and specialty pharmaceutical companies, includingAmgen, UCB S.A., Merck & Co, Novartis, Lilly, Pfizer, Roche, Asahi Kasei, Corium and Zosano, that currently market and/or are seeking to develop products forsimilar indications. Many of our competitors have substantially more resources than we do, including financial, manufacturing, marketing, research and drugdevelopment resources. In addition, many of these companies have longer operating histories and more experience than us in preclinical and clinical development,manufacturing, regulatory and global commercialization.Abaloparatide There are two main types of osteoporosis drugs currently available in the United States, anti-resorptive agents and anabolic agents. Anti-resorptive agentsincluding bisphosphonates, estrogen, SERMs and Amgen's Prolia are the most common treatments for osteoporosis. Lilly's Forteo, is the only anabolic drugapproved in the United States for the treatment of osteoporosis. In addition, there are other organizations working to develop new therapies to treat osteoporosis. InApril 2012, UCB and Amgen started a Phase 3 clinical trial program for their anti-sclerostin antibody for the treatment of osteoporosis. We are also aware of atleast one biosimilar to Lilly's Forteo, which is currently under review by the EMA. In addition, we are aware that Corium and Zosano are developing a transdermalform of PTH(1-34) that would compete with abaloparatide-TD.17Table of ContentsRAD1901 RAD1901 for the treatment of breast cancer will face competition from SERDs, CNS-penetrant anti-cancer agents and from chemotherapy derivatives.AstraZeneca's Faslodex is the only SERD currently approved in the United States for the treatment of metastatic breast cancer. In addition, there are otherorganizations working to develop new therapies to treat metastatic breast cancer, including Roche, which is developing two oral SERD's which are currently inPhase 1 and Phase 2 clinical development. RAD1901 for the treatment of vasomotor systems will face competition from recently launched products including Pfizer's Duavee and Premarin, and NovenTherapeutic's Brisdelle. We cannot assure you that our current investigational product candidates, if successfully developed and approved, will be able to compete effectively againstthese, or any other competing therapeutics that may become available on the market.Collaborations and License AgreementsNordic Bioscience Abaloparatide-SC Phase 3 Clinical Trial —We have entered into agreements with Nordic Bioscience Clinical Development VII A/S, or Nordic, to conductthe ACTIVE trial. On March 29, 2011, we entered into a Clinical Trial Services Agreement, or the Clinical Trial Services Agreement. On the same date, we alsoentered into Work Statement NB-1, as amended on December 9, 2011, June 18, 2012, March 28, 2014, May 19, 2014, July 22, 2014, August 15, 2014 andMarch 12, 2015, or Work Statement NB-1, and the Stock Issuance Agreement, as amended and restated on May 16, 2011, and as further amended on February 21,2013, March 28, 2014, and May 19, 2014, or the Stock Issuance Agreement. Abaloparatide-SC Phase 3 Clinical Extension Study —On February 21, 2013, we entered into the Work Statement NB-3, as amended on February 28, 2014,March 23, 2015, July 8, 2015 and October 21, 2015, or the Work Statement NB-3. Pursuant to the Work Statement NB-3, Nordic performed the ACTIVExtend trialfollowing the completion of the ACTIVExtend, and, upon completion of the ACTIVExtend trial, an additional period of 18 months of standard-of-care osteoporosismanagement, or the Second Extension. In April 2015, we entered into an amendment to the Work Statement NB-3, or the NB-3 Amendment. The NB-3 Amendment was effective as of March 23,2015 and provides that Nordic will perform additional services, including monitoring of patients enrolled in the Second Extension. Payments in cash to be made toNordic under the NB-3 Amendment are denominated in euros and total up to approximately €4.1 million ($4.5 million). Payments in cash to be made to Nordic under the Work Statement NB-3, are denominated in both euros and U.S. dollars and total up to €11.9 million($12.9 million) and $1.1 million, respectively. In addition, payments are due to Nordic in connection with the Work Statement NB-3 pursuant to the Stock IssuanceAgreement, as discussed below. Stock Issuance Agreement —Pursuant to the Stock Issuance Agreement, Nordic agreed to purchase 6,443 shares of our Series A-5 convertible preferred stock,which provided them with the right to receive quarterly stock dividends, payable in shares of our Series A-6 convertible preferred stock, for services rendered underWork Statement NB-1 and Work Statement NB-3. The Stock Issuance Agreement was later amended to provide that in the event an initial public offering of ourcommon stock occurred prior to June 30, 2014, any rights to receive stock dividends in relation to Work Statement NB-1 and Work Statement NB-3, for all periodsof time after 2014, would be changed from the right to receive stock to the right to receive a total cash payment of $4.3 million, payable in ten equal monthlyinstallments of $430,000 beginning on March 31, 2015. The amendment also stipulated18Table of Contentsthat all consideration to be paid to Nordic pursuant to the Stock Issuance Agreement at any time after the consummation of an initial public offering be payable incash. As we completed an initial public offering on June 11, 2014, Nordic no longer has the right to receive stock and has been paid in cash for all periods afterJune 11, 2014.3M In June 2009, we entered into a Development and Clinical Supplies Agreement with 3M under which 3M is responsible for the development of anabaloparatide-TD product and the manufacture of clinical and toxicology supplies of the abaloparatide-TD product for preclinical, Phase 1 and Phase 2 studies onan exclusive basis during the term of the Development and Clinical Supplies Agreement. In December 2012, we entered into an amendment to the Developmentand Clinical Supplies Agreement in which 3M agreed to develop and manufacture clinical and toxicology supplies for the Phase 3 abaloparatide-TD clinical study.In addition, 3M agreed that it will not use jointly owned intellectual property developed during and resulting from its work with us on abaloparatide-TD in relationto any other PTH or PTHrP analogue or derivative. We hold exclusive worldwide rights to this use of the 3M transdermal technology. We pay 3M for services delivered pursuant to the Development and Clinical Supplies Agreement on a fee-for-service or a fee-for-deliverable basis asspecified in the Development and Clinical Supplies Agreement. We have paid 3M approximately $16.7 million, in the aggregate, through December 31, 2015 inrespect to services and deliverables delivered pursuant to the Development and Clinical Supplies Agreement. The Development and Clinical Supplies Agreement, as amended, provides for services through December 31, 2017, unless it is sooner terminated. Either partymay terminate the Development and Clinical Supplies Agreement upon a material breach by the other party unless such other party cures the alleged breach withinthe notice period specified in the Development and Clinical Supplies Agreement. The Development and Clinical Supplies Agreement contains customary riskallocation clauses with 3M indemnifying us in respect of third-party claims arising from any personal injury to the extent that such claim results from 3M's breachof warranty with respect to abaloparatide-TD meeting applicable specifications; and us indemnifying 3M in respect of third-party claims arising from our or ouragent's use, testing or clinical studies of abaloparatide-TD. The Development and Clinical Supplies Agreement contains other customary clauses and terms as arecommon in similar agreements in the industry.Ipsen Pharma In September 2005, we entered into a license agreement with Ipsen, as amended on September 12, 2007 and May 11, 2011, or the License Agreement, underwhich we exclusively licensed certain Ipsen compound technology and related patents covering abaloparatide to research, develop, manufacture and commercializecertain compounds and related products in all countries, except Japan (where we do not hold abaloparatide-SC development and commercialization rights) andFrance (where our commercialization rights are subject to certain co-marketing and co-promotion rights exercisable by Ipsen, provided that certain conditionsincluded in the License Agreement have been met). Ipsen also granted us an exclusive right and license under the Ipsen compound technology and related patents tomake and have made compounds or product in Japan. Ipsen also granted us an exclusive right and license under certain Ipsen formulation technology and relatedpatents solely for purposes of enabling us to develop, manufacture and commercialize compounds and products covered by the compound technology license in allcountries, except Japan (where we do not hold abaloparatide-SC development and commercialization rights) and France (where our commercialization rights aresubject to certain co-marketing and co-promotion rights exercisable by Ipsen, provided that certain conditions included in the License Agreement have been met).With respect to France, if Ipsen exercises its co-marketing and19Table of Contentsco-promotion rights, then Ipsen may elect to receive a percentage of the net sales of the product by both parties in France (subject to a mid-double digit percentagecap), and Ipsen shall bear a corresponding percentage of the costs and expenses incurred by both parties with respect to such marketing and promotion efforts inFrance; Ipsen shall also pay us a mid-single digit royalty on Ipsen's allocable portion of net sales of the product by both parties in France. Specifically, we licensedUS Patent No. 5,969,095 (statutory term expires March 29, 2016), entitled "Analogs of Parathyroid Hormone," US Patent No. 6,544,949 (statutory term endsMarch 29, 2016), entitled "Analogs of Parathyroid Hormone," and the corresponding foreign patents and continuing patent applications. European PatentNo. 0847278, which was included in the license from Ipsen and claimed the composition of matter of abaloparatide, lapsed due to Ipsen's failure to pay annuities.We are pursuing restoration of those rights. To date, the patent rights in Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands,Portugal, Spain, Sweden, and the United Kingdom have been restored. We believe that the data and market exclusivity provided in Europe for a new chemicalentity, coupled with the need for a potential competitor to conduct clinical trials, will likely provide a longer barrier to entry than the patent protection provided bythe original European patent term, which will expire in 2016. We also have rights to joint intellectual property related to abaloparatide, including rights to the jointly derived intellectual property contained in US PatentNo. 7,803,770 (statutory term expires October 3, 2027 which we expect will be extended to March 26, 2028 with 175 days of patent term adjustment due to delaysin patent prosecution by the USPTO), US Patent No. 8,148,333 (statutory term expires October 3, 2027 which we expect will be extended to November 8, 2027with 36 days of patent term adjustment due to delays in patent prosecution by the USPTO) and related patents and patent applications both in the United States andworldwide that cover the method of treating osteoporosis using the ACTIVE trial dosage strength and form. Two corresponding European applications are pendingwith claims to the intended therapeutic formulation for abaloparatide-SC. Examination has been requested, and substantive examination has commenced for oneapplication and has not yet commenced for the other one. Upon grant, these patents could be validated in any designated contracting or extension states andpotentially could be considered for a Supplemental Protection Certificate depending upon the timing of its grant. Related cases granted in Australia, China, Israel,Japan, South Korea, Mexico, New Zealand, Russia, Singapore, and Ukraine, and currently pending in Brazil, Canada, Europe, Hong Kong, India, South Korea,Norway, and Singapore, will have a patent expiration date of 2027. Patent applications which cover various aspects of abaloparatide for microneedle application arepending in the United States, Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, South Korea, Mexico, New Zealand, Russia, Singapore,and Ukraine. Any patents that might issue from these applications will have a statutory expiration date in 2032, not taking into account extension under anyapplicable laws. In consideration for the rights to abaloparatide and in recognition of certain milestones having been met to date, we have paid to Ipsen an aggregate amount of$1.0 million. The license agreement further requires us to make payments upon the achievement of certain future clinical and regulatory milestones. The range ofmilestone payments that could be paid under the agreement is €10.0 million to €36.0 million ($10.9 million to $39.1 million). Should abaloparatide be approvedand subsequently become commercialized, we or our sublicensees will be obligated to pay to Ipsen a fixed five percent royalty based on net sales of the product ona country-by-country basis until the later of the last to expire of the licensed patents or for a period of 10 years after the first commercial sale of the licensedproducts in such country. The date of the last to expire of the abaloparatide patents licensed from or co-owned with Ipsen, barring any extension thereof, isexpected to be March 26, 2028. In the event that we sublicense abaloparatide to a third party, we are obligated to pay a percentage of certain payments receivedfrom such sublicensee (in lieu of milestone payments not achieved at the time of such sublicense). The applicable percentage is in the low double digit range. Inaddition, if we or our sublicensees commercialize a product that includes a compound discovered by us based on or derived20Table of Contentsfrom confidential Ipsen know-how, we will be obligated to pay to Ipsen a fixed low single digit royalty on net sales of such product on a country-by-country basisuntil the later of the last to expire of our patents that cover such product or for a period of 10 years after the first commercial sale of such product in such country.The license agreement contains other customary clauses and terms as are common in similar agreements in the industry. The License Agreement expires on a country-by-country basis on the later of (1) the date the last remaining valid claim in the licensed patents expires in thatcountry; or (2) a period of 10 years after the first commercial sale of the licensed products in such country, unless it is sooner terminated. The License Agreement may be terminated by us with prior notice to Ipsen. The License Agreement may be terminated by Ipsen upon notice to us withimmediate effect, if we, in any country of the world, bring an action or proceeding seeking to have any Ipsen patent right declared invalid or unenforceable. TheLicense Agreement can also be terminated by Ipsen if we fail to use reasonable commercial efforts to develop the licensed product for sale and commercializationin those countries within the territory where it is commercially reasonable to do so as contemplated by the License Agreement, or fail to use reasonable commercialefforts to perform our obligations under the latest revised version of the development plan approved by the joint steering committee, or fail to use reasonablecommercial efforts to launch and sell one licensed product in those countries within the territory where it is commercially reasonable to do so. Either party may alsoterminate the License Agreement upon a material breach by the other party unless such other party cures the alleged breach within the notice period specified in thelicense agreement. Ipsen may terminate the License Agreement in the event that the License Agreement is assigned or sublicensed or in the event that a third partyacquires us or in the event that we acquire control over a PTH or a PTHrP compound that is in clinical development or is commercially available in the territory andthat, following such assignment, sublicense, acquisition, or acquisition of control by us, such assignee, sublicensee, acquirer or we fail to meet the timetable underthe latest revised version of the development plan approved by the joint steering committee under the License Agreement. Any failure to meet such timetable forpurposes of such termination clause is deemed a material breach by us. The License Agreement contains customary risk allocation clauses with each party indemnifying the other in respect of third-party claims arising out of orresulting from: (1) the gross negligence or willful misconduct of such party, its affiliates, licensees, distributors or contractors; (2) any breach by such party of itsrepresentations and warranties or any other provision of the License Agreement or any related agreement; (3) the manufacture on behalf of such party of anylicensed product or compound; (4) (in the case of Ipsen) the use, development, handling or commercialization of any licensed compound, licensed product or theIpsen formulation technology by or on behalf of Ipsen or any of its affiliates, licensees, distributors or contractors; and (5) (in our case) the making, use,development, handling or commercialization of any licensed compound or any licensed product by or on our behalf or any of our affiliates, licensees or contractors.The license agreement contains other customary clauses and terms as are common in similar agreements in the industry. Prior to executing the License Agreement for abaloparatide with Radius, Ipsen licensed the Japanese rights for abaloparatide to Teijin Limited, or Teijin, aJapanese pharmaceutical company. Teijin has completed a Phase 2 clinical study of abaloparatide in Japan for the treatment of postmenopausal osteoporosis.Eisai In June 2006, we exclusively licensed the worldwide rights to research, develop, manufacture and commercialize RAD1901 and related products from Eisai,or the Eisai Agreement. Our license with Eisai did not originally include rights for Japan, however, on March 9, 2015, we entered into an amendment to the EisaiAgreement in which Eisai granted us an exclusive right and license to research,21Table of Contentsdevelop, manufacture and commercialize RAD1901 in Japan, or the Eisai Amendment. Specifically, we licensed the patent application that subsequently issued asUS Patent No. 7,612,114 (statutory term expires December 25, 2023 which we expect will be extended to August 18, 2026 with 967 days of patent term adjustmentdue to delays by the USPTO), entitled "Selective Estrogen Receptor Modulator," the corresponding foreign patent applications and continuing patent applications.As consideration for the rights to RAD1901, we paid Eisai an initial license fee of $0.5 million. We have also agreed to pay Eisai certain fees in the range of$1.0 million to $20.0 million (inclusive of the $0.5 million initial license fee), payable upon the achievement of certain clinical and regulatory milestones. Inconsideration for the rights to RAD1901 in Japan, we paid Eisai an initial license fee of $0.4 million upon execution of the Eisai Amendment. The EisaiAmendment also provides for additional payments, payable upon the achievement of certain clinical and regulatory milestones in Japan. Under the license with Eisai, as amended by the Eisai Amendment, or the Eisai Agreement, should a product covered by the licensed technology becommercialized, we will be obligated to pay to Eisai royalties in a variable mid-single digit range based on net sales of the product on a country-by-country basis.The royalty rate will be reduced, on a country-by-country basis, at such time as the last remaining valid claim in the licensed patents expires, lapses or isinvalidated and the product is not covered by data protection clauses. In addition, the royalty rate will be reduced, on a country-by-country basis, if, in addition tothe conditions specified in the previous sentence, lawful generic versions of such product account for more than a specified minimum percentage of the total salesof all products that contain the licensed compound during a calendar quarter. The latest patent to expire, barring any extension thereof, is expected on August 18,2026. We were also granted the right to sublicense with prior written approval from Eisai. If we sublicense the licensed technology to a third party, we will beobligated to pay Eisai, in addition to the milestone fees referenced above, a fixed low double digit percentage of certain fees we receive from such sublicensee androyalties in the low single digit range based on net sales of the sublicensee. The license agreement expires on a country-by-country basis on the later of (1) the datethe last remaining valid claim in the licensed patents expires, lapses or is invalidated in that country, the product is not covered by data protection clauses, and thesales of lawful generic version of the product account for more than a specified percentage of the total sales of all pharmaceutical products containing the licensedcompound in that country; or (2) a period of 10 years after the first commercial sale of the licensed products in such country, unless it is sooner terminated. The Eisai Agreement may be terminated by us with respect to the entire territory with prior notice to Eisai if we reasonably determine that themedical/scientific, technical, regulatory or commercial profile of the licensed product does not justify continued development or marketing. The license agreementcan also be terminated by Eisai on a country-by-country basis at any time prior to the date on which we have submitted for either an NDA approval or EMAmarketing approval with respect to a licensed product, upon prior written notice to us if Eisai makes a good faith determination that we have not used commerciallyreasonable efforts to develop the licensed product in the territory having reference to prevailing principles and time scales associated with the development, clinicaltesting and government approval of products of a like nature to such licensed product, unless such default is cured within the period specified in the EisaiAgreement or if not capable of being cured within such period we commence efforts to cure and make diligent efforts to do so. Either party may also terminate theEisai Agreement upon a material breach by the other party unless such other party cures the alleged breach within the notice period specified in the EisaiAgreement. Either party may also terminate the Eisai Agreement upon the bankruptcy or insolvency of the other party. Eisai may also terminate the EisaiAgreement with prior notice if we are acquired by, or if we transfer all of our pharmaceutical business assets (or an essential part of such assets) or more than 50%of our voting stock to, any third party person or organization, or otherwise come under the control of, such a person or organization,22Table of Contentswhether resulting from merger, acquisition, consolidation or otherwise in the event that Eisai reasonably determines that the person or organization assumingcontrol of us is not able to perform the Eisai Agreement with the same degree of skill and diligence that we would use, such determination being made withreference to the following criteria with respect to the person or organization assuming control of us: (1) whether such person or organization has the financialresources to assume our obligations with respect to development and commercialization of products; (2) whether such person or organization has personnel withskill and experience adequate to assume our obligations with respect to development and commercialization of products at the stage of development andcommercialization as of the date of such change; and (3) whether such person or organization expressly assumes all obligations imposed on us by the EisaiAgreement and agrees to dedicate personnel and financial resources to the development and commercialization of the licensed product that are at least as great asthose provided by us. Eisai shall further have the right to terminate if the acquiring person or organization: (a) has any material and active litigations with Eisai; or(b) is a hostile takeover bidder against us which has not been approved by our board of directors as constituted immediately prior to such change of control. The Eisai Agreement contains customary risk allocation. We agreed to indemnify Eisai in respect of third-party claims arising out of or resulting from:(1) negligence, recklessness or intentional acts or omissions by us, our affiliates and licensees; (2) any breach by us of a representation, warranty or covenant; and(3) any personal injury arising out of the labeling, packaging, package insert, other materials or promotional claims with respect to any licensed product by us, ouraffiliates, licensees or distributors in the territory. Eisai agreed to indemnify us for (1) negligence, recklessness or intentional acts or omissions by Eisai or itsaffiliates and licensees and (2) any breach by Eisai of a representation, warranty or covenant. The license agreement contains other customary clauses and terms asare common in similar agreements in the industry.Lonza In October 2007, we entered into a Development and Manufacturing Services Agreement with Lonza as amended in May 2011, January 2014 and December2015, or the Development and Manufacturing Service Agreement. We and Lonza have entered into a series of Work Orders pursuant to the Development andManufacturing Services Agreement pursuant to which Lonza has performed pharmaceutical development and manufacturing services for our abaloparatide product.We pay Lonza for services rendered and deliverables delivered pursuant to these work orders on a fee for service basis as specified in the applicable workstatement. The Development and Manufacturing Services Agreement will expire on March 31, 2016 unless it is sooner terminated, and is subject to renewal by usfor successive multiple-year terms with notice to Lonza. The Development and Manufacturing Services Agreement or any Work Order may be terminated by either party upon a material breach by the other partywith respect to the Development and Manufacturing Services Agreement unless such other party cures the alleged breach within the notice period specified in theDevelopment and Manufacturing Services Agreement. Either party may also terminate a Work Order if force majeure conditions have prevented performance bythe other party for more than a specified period of time with respect to such Work Order. Termination of any Work Order for force majeure shall not result intermination of the Development and Manufacturing Services Agreement or any other Work Orders, which shall remain in force until terminated. Either party mayalso terminate the Development and Manufacturing Services Agreement upon the bankruptcy or insolvency of the other party. We may also terminate theDevelopment and Manufacturing Services Agreement or any Work Order with prior notice to Lonza for convenience. We may also terminate the Development andManufacturing Services Agreement or any Work Order if we reasonably determine that Lonza is or will be unable to perform the applicable services in accordancewith the agreed upon23Table of Contentstimeframe and budget set forth in the applicable Work Order, or if Lonza fails to obtain or maintain any material governmental licenses or approvals required inconnection with such services. The Development and Manufacturing Services Agreement contains customary risk allocation clauses with each party indemnifying the other in respect ofthird-party claims arising out of or resulting from: (i) the negligence or willful misconduct of such party, its affiliates and their respective officers, directors,employees and agents in performing its obligations under the Developing and Manufacturing Services Agreement; and (ii) any breach by such party of itsrepresentations and warranties under the Development and Manufacturing Services Agreement. We have agreed to indemnify Lonza in respect of third-party claimsarising from or relating to the use of our product.Government RegulationUnited States—FDA Process The research, development, testing, manufacture, labeling, promotion, advertising, distribution and marketing, among other things, of our product candidatesare extensively regulated by governmental authorities in the United States and other countries. In the United States, the FDA regulates drugs under the FederalFood, Drug, and Cosmetic Act, or the FDCA, and its implementing regulations. Failure to comply with the applicable United States requirements may subject us toadministrative or judicial sanctions, such as FDA refusal to approve pending NDAs, warning letters, product recalls, product seizures, total or partial suspension ofproduction or distribution, injunctions, and/or criminal prosecution. We expect abaloparatide, RAD1901 and RAD140 will each be subject to review by the FDA asa drug pursuant to the NDA process, and we currently only have active IND applications in relation to abaloparatide and RAD1901 in the United States. Approval Process —None of our drugs may be marketed in the United States until the drug has received FDA approval of an NDA. The steps required to becompleted before a drug may be marketed in the United States include, among others:•preclinical laboratory tests, animal studies, and formulation studies, all performed in accordance with the FDA's Good Laboratory Practice, or GLP,regulations; •submission to the FDA of an IND application for human clinical testing, which must become effective before human clinical trials may begin andmust be updated annually; •adequate and well-controlled human clinical trials to establish the safety and efficacy of the drug for each proposed indication to FDA's satisfaction;•submission to the FDA of an NDA; •satisfactory completion of an FDA pre-approval inspection of one or more clinical trial site(s) at which the drug was studied in a clinical trial(s) toassess compliance with Good Clinical Practices, or GCP, regulations; •satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the drug is produced to assesscompliance with cGMP regulations; and •FDA review and approval of the NDA. Preclinical tests include laboratory evaluation of product chemistry, toxicity, and formulation, as well as animal studies. The conduct of the preclinical testsand formulation of the compounds for testing must comply with federal regulations and requirements. The results of the preclinical tests, together withmanufacturing information and analytical data, are submitted to the FDA as part of an IND application, which must become effective before human clinical trialsmay begin. An IND application will automatically become effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questionsabout issues such as the conduct of the trials as outlined in24Table of Contentsthe IND application. In such a case, the IND application sponsor and the FDA must resolve any outstanding FDA concerns or questions before clinical trials canproceed. We cannot be sure that submission of an IND application will result in the FDA allowing clinical trials to begin. Clinical trials involve the administration of the investigational drug to human subjects under the supervision of qualified investigators. Clinical trials areconducted under GCP pursuant to protocols detailing the objectives of the study, the parameters to be used in monitoring safety, and the effectiveness criteria to beevaluated. Each protocol must be submitted to the FDA as part of the IND application. Clinical trials necessary for product approval are typically conducted in three sequential phases, but the Phases may overlap. The study protocol and informedconsent information for study subjects in clinical trials must also be approved by an Institutional Review Board, or IRB, for each institution where the trials will beconducted, and each IRB must monitor the study until completion. Study subjects must provide informed consent and sign an informed consent form beforeparticipating in a clinical trial. Clinical testing also must satisfy the extensive GCP regulations for informed consent and privacy of individually identifiableinformation. Phase 1 usually involves the initial introduction of the investigational drug into people to evaluate its short-term safety, dosage tolerance, metabolism,pharmacokinetics and pharmacologic actions, and, if possible, to gain an early indication of its effectiveness. Phase 1 studies are usually conducted in healthyindividuals and are not intended to treat disease or illness. However, Phase 1b studies are conducted in healthy volunteers or in patients diagnosed with the diseaseor condition for which the study drug is intended, who present some biomarker, surrogate, or possibly clinical outcome that could be considered for "proof ofconcept." Proof of concept in a Phase 1b study typically confirms the hypothesis that the current prediction of biomarker, or outcome benefit is compatible with themechanism of action. Phase 2 usually involves trials in a limited patient population to: (1) evaluate dosage tolerance and appropriate dosage; (2) identify possible adverse effects andsafety risks; and (3) evaluate preliminarily the efficacy of the drug for specific target indications. Several different doses of the drug may be looked at in Phase 2 tosee which dose has the desired effects. Patients are monitored for side effects and for any improvement in their illness, symptoms, or both. Phase 3 trials usually further evaluate clinical efficacy and test further for safety by using the drug in its planned commercial form in an expanded patientpopulation. A Phase 3 trial usually compares how well the study drug works compared with an inactive placebo and/or another approved medication. One group ofpatients may receive the investigational new drug being tested, while another group of patients may receive the comparator drug (already approved drug for thedisease being studied), or placebo. There can be no assurance that Phase 1, Phase 2 or Phase 3 testing will be completed successfully within any specified period of time, if at all. Furthermore,we or the FDA or an IRB (with respect to a particular study site) may suspend clinical trials at any time on various grounds, including a finding that the subjects orpatients are being exposed to an unacceptable health risk. Assuming successful completion of the required clinical testing, the results of the preclinical studies and of the clinical studies, together with other detailedinformation, including information on the manufacture and composition of the drug, are submitted to the FDA in the form of an NDA requesting approval tomarket the product for one or more proposed indications. The testing and approval process requires substantial time, effort and financial resources. The FDAreviews the application and may deem it to be inadequate, and companies cannot be sure that any approval will be granted on a timely basis, if at all. The FDA mayalso refer the application to an appropriate advisory committee, typically a panel of clinicians, for review, evaluation and a recommendation as to whether25Table of Contentsthe application should be approved. The FDA is not bound by the recommendations of the advisory committee, but the Agency historically has tended to followsuch recommendations. The FDA has various programs, including fast track designation, breakthrough therapy designation, priority review and accelerated approval, which areintended to expedite or simplify the process for reviewing drugs and/or provide for approval on the basis of surrogate endpoints. Generally, drugs that may beeligible for one or more of these programs are those intended to treat serious or life-threatening diseases or conditions, those with the potential to address unmetmedical needs for those disease or conditions, and those that provide meaningful benefit over existing treatments. For example, a sponsor may be granted FDAdesignation of a drug candidate as a "breakthrough therapy" if the drug candidate is intended, alone or in combination with one or more other drugs, to treat aserious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existingtherapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. If a drug is designated asbreakthrough therapy, FDA will expedite the development and review of such drug. From time to time, we anticipate applying for such programs where we believewe meet the applicable FDA criteria. A company cannot be sure that any of its drugs will qualify for any of these programs, or even if a drug does qualify, that thereview time will be reduced. Before approving an NDA, the FDA usually will inspect the facility or the facilities at which the drug is manufactured and will not approve the product unlessthe manufacturing and production and testing facilities are in compliance with cGMP regulations. If the NDA and the manufacturing facilities are deemedacceptable by the FDA, it may issue an approval letter, or in some cases, a Complete Response Letter. An approval letter authorizes commercial marketing of thedrug with specific prescribing information for a specific indication(s). A Complete Response Letter indicates that the review cycle of the application is completeand the application is not ready for approval. A Complete Response Letter may require additional clinical data and/or an additional pivotal Phase 3 clinical trial(s),and/or other significant, expensive and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. Even if such additionalinformation is submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. The FDA could also require, as a condition ofNDA approval, post-marketing testing and surveillance to monitor the drug's safety or efficacy, or impose other conditions. Approval may also be contingent on aRisk Evaluation and Mitigation Strategy, or REMS, that limits the labeling, distribution or promotion of a drug product. The FDA also may condition approval on,among other things, changes to proposed labeling, development of adequate controls and specifications, or a commitment to conduct one or more post-marketingstudies or clinical trials. Once issued, the FDA may withdraw product approval if ongoing regulatory requirements are not met or if safety problems occur after theproduct reaches the market. After approval, certain changes to the approved product, such as adding new indications, making certain manufacturing changes or making certain additionallabeling claims, are subject to further FDA review and approval. Before a company can market products for additional indications, it must obtain additionalapprovals from the FDA. Obtaining approval for a new indication generally requires that additional clinical studies be conducted. A company cannot be sure thatany additional approval for new indications for any investigational product candidate will be approved on a timely basis, or at all. Post-Approval Requirements —Often times, even after a drug has been approved by the FDA for sale, the FDA may require that certain post-approvalrequirements be satisfied, including the conduct of additional clinical studies. If such post-approval conditions are not satisfied, the FDA may withdraw its approvalof the drug. In addition, holders of an approved NDA are required to: (1) report certain adverse reactions to the FDA, (2) comply with certain requirementsconcerning advertising and promotional labeling for their products, and (3) continue to have quality control and manufacturing procedures conform to cGMPregulations after approval. The FDA periodically inspects the sponsor's26Table of Contentsrecords related to safety reporting and/or manufacturing facilities; this latter effort includes assessment of ongoing compliance with cGMP regulations.Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance. We haveused and intend to continue to use third-party manufacturers to produce our products in clinical and commercial quantities, and future FDA inspections mayidentify compliance issues at the facilities of our contract manufacturers that may disrupt production or distribution, or require substantial resources to correct. Inaddition, discovery of problems with a product after approval may result in restrictions on a product, including recall or withdrawal of the product from the market. Hatch-Waxman Act —Under the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act, Congress createdan abbreviated FDA review process for generic versions of pioneer (brand name) drug products. In considering whether to approve such a generic drug product, theFDA requires that an Abbreviated New Drug Application, or ANDA, applicant demonstrate, among other things, that the proposed generic drug product's activeingredient is the same as that of the reference product, that any impurities in the proposed product do not affect the product's safety or effectiveness, and that itsmanufacturing processes and methods ensure the consistent potency and purity of its proposed product. The Hatch-Waxman Act provides five years of data exclusivity for new chemical entities, which generally (except as discussed below) prevents the FDA fromaccepting ANDAs and 505(b)(2) applications containing the protected active ingredient during the five-year period. We expect to be eligible for five years of dataexclusivity following any FDA approval of abaloparatide-SC. The Hatch-Waxman Act also provides three years of exclusivity for applications containing the results of new clinical investigations (other than bioavailabilitystudies) essential to the FDA's approval of new uses of approved products, such as new indications, delivery mechanisms, dosage forms, strengths, or conditions ofuse. For example, if abaloparatide-SC is approved for commercialization and we are successful in performing a clinical trial of abaloparatide-TD that provides anew basis for approval (a different delivery mechanism), it is possible that we may become eligible for a three year period of market exclusivity which protectsagainst the approval (but not the filing) of ANDAs and 505(b)(2) applications for the protected use but will not prohibit the FDA from accepting or approvingANDAs or 505(b)(2) applications for other products containing the same active ingredient. The Hatch-Waxman Act requires NDA applicants and NDA holders to provide certain information about patents related to the drug for listing in the FDA's listof Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book). ANDA and 505(b)(2) applicants must then certifyregarding each of the patents listed with the FDA for the reference product. A certification that a listed patent is invalid and/or will not be infringed by themarketing of the applicant's product is called a "Paragraph IV certification." If the ANDA or 505(b)(2) applicant provides such a notification of patent invalidity ornon-infringement, then the FDA may accept the ANDA or 505(b)(2) application beginning four years after approval of the NDA. If an ANDA or 505(b)(2)application containing a Paragraph IV certification is submitted to the FDA and accepted as a reviewable filing by the Agency, the ANDA or 505(b)(2) applicantthen must provide, within 20 days, notice to the NDA holder and patent owner stating that the application has been submitted and providing the factual and legalbasis for the applicant's opinion that the patent is invalid and/or not infringed. The NDA holder or patent owner then may file suit against the ANDA or 505(b)(2)applicant for patent infringement. If this is done within 45 days of receiving notice of the Paragraph IV certification, a one-time 30-month stay of the FDA's abilityto approve the ANDA or 505(b)(2) application is triggered. The 30-month stay begins at the end of the NDA holder's data exclusivity period, or, if data exclusivityhas expired, on the date that the patent holder is notified of the submission of the ANDA. The FDA may approve the proposed product before the expiration of the30-month stay if a court finds the patent invalid and/or not infringed or if the court shortens the period because the parties have failed to cooperate in expediting thelitigation.27Table of ContentsEuropean Union—EMA Process In the EU, medicinal products are authorized following a similar demanding process as that required in the United States and applications are based on theICH Common Technical Document. In the European Economic Area, or EEA (comprised of 28 EU Member States plus Iceland, Liechtenstein and Norway),medicines can be authorized by using either the centralized authorization procedure or national authorization procedures. Centralized procedure —Under the centralized procedure, following the opinion of the EMA's Committee for Medicinal Products for Human Use (CHMP),the European Commission issues a single marketing authorization valid across the EEA. The centralized procedure is compulsory for human medicines derivedfrom biotechnology processes, advanced therapy medicinal products (such as gene therapy, somatic cell therapy and tissue engineered products), containing a newactive substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, or neurodegenerative disorders, diabetes, autoimmune diseases andother immune dysfunctions, viral diseases, and officially designated orphan medicines. For medicines that do not fall within these categories, an applicant has theoption of submitting an application for a centralized marketing authorization to the EMA, as long as the medicine concerned contains a new active substance notyet authorized in the EEA, is a significant therapeutic, scientific or technical innovation, or if its authorization would be in the interest of public health in the EEA.In November 2015, we submitted an MAA for abaloparatide-SC to the EMA under the centralized procedure. The MAA was validated in December 2015 and iscurrently undergoing regulatory review by the EMA. National authorization procedures —There are also two other possible routes to authorize medicinal products in several countries, which are available forproducts that fall outside the scope of the centralized procedure:•Decentralized procedure. Using the decentralized procedure, an applicant may apply for simultaneous authorization in more than one EU countryof a medicinal product that has not yet been authorized in any EU country and that does not fall within the mandatory scope of the centralizedprocedure. •Mutual recognition procedure. In the mutual recognition procedure, a medicine is first authorized in one EU Member State, in accordance with thenational procedures of that country. Thereafter, further marketing authorizations can be sought from other EU countries in a procedure whereby thecountries concerned agree to recognize the validity of the original, national marketing authorization. In light of the fact that there is no policy at the EU level governing pricing and reimbursement, the 28 EU Member States each have developed their own, oftenvarying, approaches. In many EU Member States, pricing negotiations must take place between the holder of the marketing authorization and the competentnational authorities before the product is sold in their market with the holder of the marketing authorization required to provide evidence demonstrating thepharmaco-economic superiority of its product in comparison with directly and indirectly competing products. We have reviewed our development program,proposed Phase 3 study design, and overall non-clinical and clinical data package and believe they support future regulatory approval of abaloparatide-SC in theEU. Good manufacturing practices —Like the FDA, the EMA, the competent authorities of the EU Member States and other regulatory agencies regulate andinspect equipment, facilities and processes used in the manufacturing of pharmaceutical and biologic products prior to approving a product. If, after receivingclearance from regulatory agencies, a company makes a material change in manufacturing equipment, location, or process, additional regulatory review andapproval may be required. Once we or our partners commercialize products, we will be required to comply with cGMP,28Table of Contentsand product-specific regulations enforced by, the European Commission, the EMA and the competent authorities of EU Member States following product approval.Also like the FDA, the EMA, the competent authorities of the EU Member States and other regulatory agencies also conduct regular, periodic visits to re-inspectequipment, facilities, and processes following the initial approval of a product. If, as a result of these inspections, it is determined that our or our partners'equipment, facilities, or processes do not comply with applicable regulations and conditions of product approval, regulatory agencies may seek civil, criminal oradministrative sanctions and/or remedies against us, including the suspension of our manufacturing operations or the withdrawal of our product from the market. Data and Market Exclusivity —Similar to the United States, there is a process for approval of generic versions of innovator drug products in the EU. Abridgedapplications for the authorization of generic versions of drugs authorized by EMA can be submitted to the EMA through the centralized procedure referencing theinnovator's data and demonstrating bioequivalence to the reference product, among other things. New medicinal products in the EU can receive eight years of data exclusivity coupled with two years of market exclusivity, and a potential one year extension,if the marketing authorizations holder obtains an authorization for one or more new therapeutic indications that demonstrates "significant clinical benefit" incomparison with existing therapies; this system is usually referred to as "8+2+1". We expect to be eligible for at least ten years of exclusivity (8 years of dataexclusivity + 2 years of market exclusivity) following any approval of abaloparatide-SC. At this time we do not believe that there are orphan or pediatricapplications for abaloparatide that would be likely to result in a grant of exclusivity or supplemental protection certificate in the EU. Abridged applications cannot rely on an innovator's data until after expiry of the 8-year data exclusivity term; applications for a generic product can besubmitted after that 8 th year, but the product cannot be marketed until the end of the market exclusivity term.Other International Markets—Drug approval process In some international markets (e.g., China or Japan), although data generated in United States or EU trials may be submitted in support of a marketingauthorization application, additional clinical trials conducted in the host territory, or studying people of the ethnicity of the host territory, may be required prior tothe filing or approval of marketing applications within the country.Pricing and Reimbursement In the United States and internationally, sales of products that we market in the future, and our ability to generate revenues on such sales, are dependent, insignificant part, on the availability and level of coverage and reimbursement from third-party payors such as state and federal governments, managed care providersand private insurance plans. Private insurers, such as health maintenance organizations and managed care providers, have implemented cost-cutting andreimbursement initiatives and likely will continue to do so in the future. These include establishing formularies that govern the drugs and biologics that will beoffered and also the out-of-pocket obligations of member patients for such products. In addition, particularly in the United States and increasingly in othercountries, we may be required to provide discounts and pay rebates to state and federal governments and agencies in connection with purchases of our products thatare reimbursed by such entities. It is possible that future legislation in the United States and other jurisdictions could be enacted which could potentially impact thereimbursement rates for the products we are developing and may develop in the future and also could further impact the levels of discounts and rebates paid tofederal and state government entities. Any legislation that impacts these areas could impact, in a significant way, our ability to generate revenues from sales ofproducts that, if successfully developed, we bring to market.29Table of Contents The Medicare Prescription Drug, Improvement, and Modernization Act of 2003, or MMA, established the Medicare Part D program to provide a voluntaryprescription drug benefit to Medicare beneficiaries. Under Part D, Medicare beneficiaries may enroll in prescription drug plans offered by private entities toprovide coverage of outpatient prescription drugs. Part D plans include both stand-alone prescription drug benefit plans and prescription drug coverage as asupplement to Medicare Advantage plans. Unlike Medicare Parts A and B, Part D coverage is not standardized. Part D prescription drug plan sponsors are notrequired to pay for all covered Part D drugs, and each Part D prescription drug plan can develop its own drug formulary that identifies which drugs it will cover andat what tier or level. However, Part D prescription drug formularies must include drugs within each therapeutic category and class of covered Part D drugs,although not necessarily all of the drugs within each category or class. Any formulary used by a Part D prescription drug plan must be developed and reviewed by apharmacy and therapeutic committee. We anticipate that a significant proportion of patients eligible for abaloparatide-SC will be Medicare beneficiaries and weexpect that abaloparatide-SC, if approved, will be covered under Medicare Part D, although we cannot assure you that Part D prescription drug plan sponsors willcover abaloparatide-SC, or, if covered, at what tier or level. Government payment for some of the costs of prescription drugs may increase demand for any of our products that is successfully developed and approved.However, any negotiated prices for our products covered by a Part D prescription drug plan will likely be lower than the prices we might otherwise obtain.Moreover, although the MMA applies only to drug benefits for Medicare beneficiaries, private payers often follow Medicare coverage policy and paymentlimitations in setting their own payment rates. Accordingly, any reduction in payment under Medicare may result in a similar reduction in payments from non-governmental payers. We expect that there will continue to be a number of federal and state proposals to implement governmental pricing controls and limit the growth of healthcarecosts, including the cost of prescription drugs. Currently, Medicare is prohibited from negotiating directly with pharmaceutical companies for drugs. However, theU.S. Congress may in the future consider legislation that would lift the ban on federal negotiations. The American Recovery and Reinvestment Act of 2009 provides funding for the federal government to compare the effectiveness of different treatments forthe same illness. A plan for the research would be developed by the Department of Health and Human Services, the Agency for Healthcare Research and Qualityand the National Institutes of Health, and periodic reports on the status of the research and related expenditures would be made to the U.S. Congress. Although theresults of the comparative effectiveness studies are not intended to mandate coverage policies for public or private payers, it is not clear whether research wouldhave any effect on the sales of any of our products that is successfully developed and approved, if the product or the condition that it is intended to treat becomesthe subject of a study. It is also possible that comparative effectiveness research demonstrating benefits of a competitor's product could adversely affect the sales ofany of our products that is successfully developed and approved. If third-party payers do not consider our products to be cost-effective compared to other availabletherapies, they may not cover our products after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sellour products on a profitable basis. The Patient Protection and Affordable Care Act, or the ACA, as amended by the Health Care and Education Affordability Reconciliation Act of 2010, orcollectively the ACA, is expected to have a significant impact on the health care industry. The ACA expands coverage for the uninsured while at the same timecontaining overall healthcare costs. Among other things, the ACA expands and increases industry rebates for drugs covered under Medicaid programs and makechanges to the coverage requirements under the Medicare Part D program. In addition, other legislative changes have been proposed and adopted in the UnitedStates since the ACA was enacted. On August 2, 2011, the Budget30Table of ContentsControl Act of 2011, among other things, created measures for spending reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked withrecommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering thelegislation's automatic reduction to several government programs. This includes aggregate reductions to Medicare payments to providers of 2% per fiscal year,which went into effect on April 1, 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2025 unless additionalCongressional action is taken. On January 2, 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, or the ATRA, which among otherthings, further reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers. There is no legislation at the EU level governing the pricing and reimbursement of medicinal products in the EU. As a result, the competent authorities of eachof the 28 EU Member States have adopted individual strategies regulating the pricing and reimbursement of medicinal products in their territory. These strategiesoften vary widely in nature, scope and application. However, a major element that they have in common is an increased move towards reduction in thereimbursement price of medicinal products, a reduction in the number and type of products selected for reimbursement, and an increased preference for genericproducts over innovative products. These efforts have mostly been executed through these countries' existing price-control methodologies, including price cuts,mandatory rebates, value-based pricing, and reference pricing (i.e., referencing prices in other countries and using those reference prices to set a price). Thegovernment of the UK announced the phase-out of its established Pharmaceutical Pricing Reimbursement Scheme approach in January 2014 and the adoption of anew value-based pricing approach, at least for new product introductions. Under this approach, in a complete departure from established methodologies,reimbursement levels of each drug will be explicitly based on an assessment of value, looking at the benefits for the patient, unmet need, therapeutic innovation,and benefit to society as a whole. It is increasingly common in many EU Member States for Marketing Authorization Holders to be required to demonstrate thepharmaco-economic superiority of their products as compared to products already subject to pricing and reimbursement in specific countries. In order for drugs tobe evaluated positively under such criteria, pharmaceutical companies may need to re-examine, and consider altering, a number of traditional functions relating tothe selection, study, and management of drugs, whether currently marketed, under development, or being evaluated as candidates for research and/or development. Future legislation, including the current versions being considered at the federal and state level in the United States and at the national level in EU MemberStates, or regulatory actions implementing recent or future legislation may have a significant effect on our business. Our ability to successfully commercializeproducts depends in part on the extent to which coverage and reimbursement for the costs of our products and related treatments will be available in the UnitedStates and worldwide from government health administration authorities, private health insurers and other organizations. Substantial uncertainty exists as to thereimbursement status of newly approved healthcare products by third-party payors. In addition, negotiating prices with government authorities under current andproposed legislation can delay the commercialization of our product candidates.Sales and Marketing The FDA regulates all advertising and promotion activities for products under its jurisdiction both prior to and after approval. A company can make only thoseclaims relating to safety and efficacy that are approved by the FDA following review and approval of an NDA. Physicians may prescribe legally available drugs foruses that are not described in the drug's labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medicalspecialties, and often reflect a physician's belief that the off-label use is the best treatment for the patients. The FDA does not regulate the behavior of physicians intheir choice of treatments, but FDA regulations do impose31Table of Contentsstringent restrictions on manufacturers' communications regarding off-label uses. Failure to comply with applicable FDA requirements may subject a company toadverse publicity, enforcement action by the FDA, corrective advertising, consent decrees and the full range of civil and criminal penalties available to the FDA. We may also be subject to various federal and state laws pertaining to healthcare "fraud and abuse," including anti-kickback laws and false claims laws. Anti-kickback laws make it illegal for a prescription drug manufacturer to solicit, offer, receive, or pay any remuneration in exchange for, or to induce, the referral ofbusiness, including the purchase or prescription of a particular drug. Due to the breadth of the statutory provisions and the absence of guidance in the form ofregulations and very few court decisions addressing industry practices, it is possible that our practices might be challenged under anti-kickback or similar laws.Moreover, recent healthcare reform legislation has strengthened these laws. For example, the ACA, among other things, amends the intent requirement of thefederal anti-kickback and criminal healthcare fraud statutes, so that a person or entity no longer needs to have actual knowledge of this statute or specific intent toviolate it in order to have committed a violation. In addition, ACA permits the government to assert that a claim that includes items or services resulting from aviolation of the federal anti-kickback statute constitutes a false or fraudulent claim for purposes of the false claims statutes. False claims laws prohibit anyone fromknowingly and willingly presenting, or causing to be presented for payment, to third-party payors (including Medicare and Medicaid) claims for reimbursed drugsor services that are false or fraudulent, claims for items or services not provided as claimed, or claims for medically unnecessary items or services. Our activitiesrelating to the sale and marketing of our products, if approved, may be subject to scrutiny under these laws. Violations of fraud and abuse laws may be punishableby criminal and civil sanctions, including fines and civil monetary penalties, the possibility of exclusion from federal healthcare programs (including Medicare andMedicaid) and corporate integrity agreements, which impose, among other things, rigorous operational and monitoring requirements on companies. Similarsanctions and penalties also can be imposed upon executive officers and employees, including criminal sanctions against executive officers under the so-called"responsible corporate officer" doctrine, even in situations where the executive officer did not intend to violate the law and was unaware of any wrongdoing. Given the significant penalties and fines that can be imposed on companies and individuals if convicted, allegations of such violations often result insettlements even if the company or individual being investigated admits no wrongdoing. Settlements often include significant civil sanctions, including fines andcivil monetary penalties, and corporate integrity agreements. If the government were to allege or convict us or our executive officers of violating these laws, ourbusiness could be harmed. In addition, private individuals have the ability to bring similar actions. The majority of states also have anti-kickback and false claimslaws, which establish similar prohibitions and in some cases may apply to items or services reimbursed by any third-party payor, including commercial insurers.Our activities could be subject to challenge for the reasons discussed above and due to the broad scope of these laws and the increasing attention being given tothem by law enforcement authorities. There has also been a recent trend of increased federal and state regulation of payments made to physicians and other healthcare providers. The ACA, amongother things, imposes new reporting requirements on drug manufacturers for payments made by them to physicians and teaching hospitals, as well as ownership andinvestment interests held by physicians and their immediate family members. Failure to submit required information may result in civil monetary penalties of up toan aggregate of $150,000 per year (or up to an aggregate of $1 million per year for "knowing failures"), for all payments, transfers of value or ownership orinvestment interests that are not timely, accurately and completely reported in an annual submission. Drug manufacturers are required to submit reports to thegovernment by the 90th day of each calendar year. Certain states also mandate implementation of compliance programs, impose restrictions on drug manufacturermarketing practices and/or require the tracking and reporting of gifts, compensation and other remuneration to physicians. Many of these laws32Table of Contentscontain ambiguities as to what is required to comply with the laws. Given the lack of clarity in laws and their implementation, our actions could be subject to thepenalty provisions of the pertinent state authorities. Similar rigid restrictions are imposed on the promotion and marketing of medicinal products in the EU and other countries. Laws (including those governingpromotion, marketing and anti-kickback provisions), industry regulations and professional codes of conduct often are strictly enforced. Even in those countrieswhere we are not directly responsible for the promotion and marketing of our products, inappropriate activity by our international distribution partners can haveadverse implications for us.Other Laws and Regulatory Processes We are subject to a variety of financial disclosure and securities trading regulations as a public company in the United States, including laws relating to theoversight activities of the SEC and the regulations of the NASDAQ Global Market or any national securities exchange on which our capital stock may be traded. Inaddition, the Financial Accounting Standards Board, or FASB, the SEC and other bodies that have jurisdiction over the form and content of our accounts, ourconsolidated financial statements and other public disclosure are constantly discussing and interpreting proposals and existing pronouncements designed to ensurethat companies best display relevant and transparent information relating to their respective businesses. Our international operations are subject to compliance with the Foreign Corrupt Practices Act, or the FCPA, which prohibits corporations and individuals frompaying, offering to pay, or authorizing the payment of anything of value to any foreign government official, government staff member, political party, or politicalcandidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity. We also may be implicated under the FCPAfor activities by our partners, collaborators, clinical research organizations, vendors or other agents. Our present and future business has been and will continue to be subject to various other laws and regulations. Various laws, regulations and recommendationsrelating to safe working conditions, laboratory practices, the experimental use of animals, and the purchase, storage, movement, import and export and use anddisposal of hazardous or potentially hazardous substances used in connection with our research work are or may be applicable to our activities. Certain agreementsentered into by us involving exclusive license rights or acquisitions may be subject to national or supranational antitrust regulatory control, the effect of whichcannot be predicted. The extent of government regulation, which might result from future legislation or administrative action, cannot accurately be predicted.Employees As of December 31, 2015, we employed 73 full-time employees and 2 part-time employees, 20 of whom held Ph.D. or M.D. degrees. Forty-eight of ouremployees were engaged in research and development activities and 27 were engaged in support administration, including business development and finance. Weintend to use CROs and other third parties to perform our clinical studies and manufacturing.Corporate Information We were incorporated in the state of Delaware on February 4, 2008 under the name MPM Acquisition Corp. In May 2011, we entered into a reverse mergertransaction, or the Merger, with our predecessor, Radius Health, Inc., a Delaware corporation formed on October 3, 2003, or the Former Operating Company,pursuant to which the Former Operating Company became a wholly-owned subsidiary of ours. Immediately following the merger transaction, the Former OperatingCompany was merged with and into us and we assumed the business of the Former Operating Company and changed our name to Radius Health, Inc.33Table of ContentsLegal Proceedings We are not currently involved in any material legal proceedings.Investor Information Financial and other information about us is available on our website at www.radiuspharm.com. We make available on our website, free of charge, copies ofour Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant toSection 13(a) or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. In addition,we have previously filed registration statements and other documents with the SEC. Any document we file may be inspected, without charge, at the SEC's publicreference room at 100 F Street NE, Washington, DC 20549, or at the SEC's internet address at www.sec.gov. These website addresses are not intended to functionas hyperlinks, and the information contained in our website and in the SEC's website is not intended to be a part of this filing. Information related to the operationof the SEC's public reference room may be obtained by calling the SEC at 800-SEC-0330.34Table of ContentsITEM 1A. RISK FACTORS. Our business faces significant risks and uncertainties. Certain important factors may have a material adverse effect on our business prospects, financialcondition and results of operations, and you should carefully consider them. Accordingly, in evaluating our business, we encourage you to consider the followingdiscussion of risk factors, in its entirety, in addition to other information contained in or incorporated by reference into this Annual Report on Form 10-K and ourother public filings with the SEC.Risks Related to Our Business Risks Related to Our Financial Position and Need for CapitalWe are not currently profitable and may never become profitable. We had net losses of $101.5 million, $62.5 million, and $60.7 million for the years ended December 31, 2015, 2014, and 2013, respectively. As ofDecember 31, 2015, we had an accumulated deficit of $445.8 million. Until we succeed in developing and commercializing one or more of our product candidates,we expect to incur substantial losses and may never achieve or maintain profitability. We also expect to continue to incur significant operating and capitalexpenditures and anticipate that our expenses will increase substantially as we:•continue to undertake preclinical development and clinical trials for product candidates; •seek regulatory approvals for product candidates; •implement additional internal systems and infrastructure; and •hire additional personnel. We also expect to experience negative cash flow as we fund our operating losses and capital expenditures. As a result, we will need to generate significantrevenues in order to achieve and maintain profitability. Accordingly, unless and until we generate revenues and become profitable, we will need to raise additionalcapital to continue to operate our business. Our failure to achieve or maintain profitability or to raise additional capital could negatively impact the value of oursecurities.We currently have no product revenues and we may need to raise additional capital, which may not be available on favorable terms, if at all, in order tocontinue operating our business. To date, we have generated no product revenues. Until, and unless, we receive approval from the U.S. Food and Drug Administration, or FDA, or foreignregulatory authorities for our product candidates, we will not be permitted to sell our drugs and will not have product revenues. Currently, our only productcandidates are abaloparatide-SC, abaloparatide-TD, RAD1901 and RAD140, and none of these product candidates is approved by the FDA or foreign regulatoryauthorities for sale. Therefore, for the foreseeable future, we will have to fund our operations and capital expenditures with our existing cash and cash equivalentsand short and long-term marketable securities, or through strategic financing opportunities, that could include, but are not limited to partnering or othercollaboration agreements, future offerings of our equity, and/or the incurrence of debt. Based upon our cash, cash equivalents and short-term marketable securities balance at December 31, 2015, we believe that, prior to the consideration ofrevenue from the potential future sales of any of our investigational products that may receive regulatory approval, we have sufficient capital to fund ourdevelopment plans, U.S. commercial scale-up and other operational activities into 2018. We have based this estimate on assumptions that may prove to be wrong,and we could use up our available capital resources sooner than we currently expect. If we fail to obtain additional capital, we may be unable to complete ourplanned preclinical and clinical trials and obtain approval of any product candidates from the FDA and foreign regulatory authorities. In addition, we could beforced to35Table of Contentsdiscontinue product development, reduce or forego sales and marketing efforts for any product candidate that is approved, forego attractive business opportunitiesor discontinue our operations entirely. Any additional sources of financing may not be available or may not be available on favorable terms and will likely involvethe issuance of additional equity securities, which will have a dilutive effect on stockholders. Our future capital requirements will depend on many factors,including the scope and progress made in our research and development activities and our clinical studies.Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies orproduct candidates. Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of collaborations,strategic alliances, licensing arrangements, other marketing and distribution arrangements, equity offerings, and debt financings. We do not have any committedexternal source of funds. To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will bediluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a stockholder. Debt financing, if available,may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capitalexpenditures or declaring dividends. If we raise additional funds through marketing and distribution arrangements or other collaborations, strategic alliances orlicensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or productcandidates, or we may need to grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financingswhen needed, we may be required to delay, limit, reduce or terminate our product development or commercialization efforts or grant rights to develop and marketproduct candidates that we would otherwise prefer to develop and market ourselves.We are a company with a limited operating history upon which to base an investment decision. We are a company with a limited operating history and have not demonstrated an ability to perform the functions necessary for the successfulcommercialization of any product candidates. The successful commercialization of any product candidates will require us to perform a variety of functions,including:•continuing to undertake preclinical development and clinical trials; •participating in regulatory approval processes; •formulating and manufacturing products; and •conducting sales and marketing activities for products if approved. Our operations have been limited to organizing and staffing our company, acquiring, developing and securing our proprietary technology and undertakingpreclinical and clinical trials of our product candidates. These operations provide a limited basis for you to assess our ability to commercialize our productcandidates and the advisability of investing further in our securities.Our financial results may fluctuate from quarter to quarter, which makes our results difficult to predict and could cause our results to fall short ofexpectations. Our financial results may fluctuate as a result of a number of factors, many of which are outside of our control. For these reasons, comparing our financialresults on a period-to-period basis may not be meaningful, and you should not rely on our past results as an indication of our future performance. Our revenues, ifany, may fluctuate from quarter to quarter and our future quarterly and annual expenses as a percentage of our revenues may be significantly different from thosewe have recorded in36Table of Contentsthe past or which we expect for the future. Our financial results in some quarters may fall below expectations. Any of these events as well as the various risk factorslisted in this "Risk Factors" section could adversely affect our financial results and cause our stock price to fall.Our cash and cash equivalents could be adversely affected if the financial institutions in which we hold our cash and cash equivalents fail. We regularly maintain cash balances at third-party financial institutions in excess of the Federal Deposit Insurance Corporation insurance limit. While wemonitor daily the cash balances in the operating accounts and adjust the balances as appropriate, these balances could be impacted, and there could be a materialadverse effect on our business, if one or more of the financial institutions with which we deposit fails or is subject to other adverse conditions in the financial orcredit markets. To date, we have experienced no loss or lack of access to our invested cash or cash equivalents; however, we can provide no assurance that accessto our invested cash and cash equivalents will not be impacted by adverse conditions in the financial and credit markets.Our investments in marketable securities are subject to market, interest and credit risk that may reduce their value. The value of our investments in marketable securities may be adversely affected by changes in interest rates, downgrades in the creditworthiness of any bondswe hold, turmoil in the credit markets and financial services industry and by other factors which may result in other than temporary declines in the value of ourinvestments. Decreases in the market value of our marketable securities could have an adverse impact on our statements of financial position, results of operationsand cash flow.Risks Related to the Discovery, Development and Commercialization of Our Product CandidatesWe are heavily dependent on the success of our investigational product candidate abaloparatide-SC. We cannot be certain that abaloparatide-SC will receiveregulatory approval or be successfully commercialized even if we receive regulatory approval. Abaloparatide-SC is our only product candidate in late-stage clinical development, and our business currently depends heavily on its successful development,regulatory approval and commercialization. We have no drug products for sale currently and may never be able to develop approved and marketable drug products.The research, testing, manufacturing, labeling, approval, sale, marketing and distribution of drug products are subject to extensive regulation by the FDA andforeign regulatory authorities in the United States and other countries, which regulations differ from country to country. We are not permitted to marketabaloparatide-SC in the United States unless and until we receive approval of a new drug application, or NDA, from the FDA, or in any foreign countries unlessand until we receive the requisite approval from regulatory authorities in those foreign countries. In addition, the approval of abaloparatide-TD as a line extensionto abaloparatide-SC is dependent on the earlier approval of abaloparatide-SC. Obtaining approval of a product candidate is an extensive, lengthy, expensive anduncertain process, and any approval of abaloparatide-SC may be delayed, limited or denied for many reasons, including:•we may not be able to demonstrate that abaloparatide is safe and effective as a treatment for reduction of fracture risk in postmenopausal womenwith osteoporosis to the satisfaction of the FDA or foreign regulatory authorities; •the results of our clinical studies may not meet the level of statistical or clinical significance required for marketing approval; •the FDA or foreign regulatory authorities may disagree with the number, design, size, conduct or implementation of our clinical studies;37Table of Contents•any clinical research organizations, or CROs, that we have retained or may in the future retain, to conduct clinical studies may take actions outsideof our control that materially adversely impact our clinical studies; •the FDA or foreign regulatory authorities may not find the data from preclinical studies and clinical studies sufficient to demonstrate thatabaloparatide's clinical and other benefits outweigh its safety risks; •the FDA or foreign regulatory authorities may disagree with our interpretation of data from our preclinical studies and clinical studies or mayrequire that we conduct additional studies; •the FDA or foreign regulatory authorities may not accept data generated at our clinical study sites; •the FDA or foreign regulatory authorities may not agree with our proposed labeling and may require labeling that undermines or otherwisesignificantly impairs the commercial value of the product if it were to be approved with such labeling; •the FDA may require development of a Risk Evaluation and Mitigation Strategy, or REMS, as a condition of approval; •if our NDA is reviewed by an advisory committee, the FDA may have difficulties scheduling an advisory committee meeting in a timely manner orthe advisory committee may recommend against approval of our application or may recommend that the FDA require, as a condition of approval,additional preclinical studies or clinical studies, limitations on approved labeling or distribution and use restrictions; or •the FDA or foreign regulatory authorities may identify deficiencies in the manufacturing processes or facilities of our third-party manufacturers. In addition, the FDA or foreign regulatory authorities may change its approval policies or adopt new regulations. For example, on February 15, 2012, wereceived a letter from the FDA stating that, after internal consideration, the FDA believes that a minimum of 24-month fracture data are necessary for approval ofnew products for the treatment of postmenopausal osteoporosis. Our abaloparatide-SC pivotal Phase 3 clinical trial is designed to produce fracture data based on an18-month primary endpoint. Based on our discussions with the FDA, we believe that continued use of the 18-month primary endpoint will be acceptable, providedthat our NDA includes the 24-month fracture data derived from the first six months extension of the abaloparatide 80 µg and placebo groups in our Phase 3 study,which groups received an approved alendronate (generic Fosamax) therapy for osteoporosis management. The NDA that we plan to submit to the FDA forabaloparatide-SC as a proposed treatment for osteoporosis will include the 24-month fracture data. We cannot be certain that the FDA will be supportive of thisplan, will not change this approval policy again or will not adopt other approval policies or regulations that adversely affect any NDA that we may submit, theoccurrence of any of which may further delay FDA approval. We cannot assure you that we will receive the approvals necessary to commercialize abaloparatide-SC, or any of our product candidates, including anyproduct candidates we are currently developing or may acquire or develop in the future. In order to obtain FDA approval of abaloparatide-SC, or any productcandidate, we must submit to the FDA an NDA demonstrating that the product candidate is safe for humans and effective for its indicated use. This demonstrationrequires significant research and animal tests, which are referred to as preclinical studies, as well as human tests, which are referred to as clinical trials. Satisfactionof the FDA's regulatory requirements typically takes many years, depends upon the type, complexity and novelty of the product candidate and requires substantialresources for research, development and testing. We cannot predict whether our38Table of Contentsresearch and clinical approaches will result in drugs that the FDA considers safe for humans and effective for proposed uses. In 2007, we entered into a global pharmacovigilance agreement with Teijin Limited, or Teijin, a Japanese pharmaceutical company, that provides for theexchange of information related to serious and non-serious adverse reactions to abaloparatide by patients enrolled in clinical studies. The purpose of the agreementis to enable safety reporting to global health agencies. Teijin has completed a Phase 2 clinical study of abaloparatide-SC in Japan for the treatment ofpostmenopausal osteoporosis. Should Teijin advise us in accordance with our agreement of a serious adverse event experienced by patients enrolled in their study,we would need to report the serious adverse event to the FDA and the European Medicines Agency, or EMA, which could adversely affect or delay our ability toobtain regulatory approvals in the United States and Europe. In addition, the FDA has substantial discretion in the drug approval process and may require us to conduct additional preclinical and clinical testing or toperform post-marketing studies. The approval process may also be delayed by changes in government regulation, future legislation or administrative action orchanges in FDA policy that occur prior to or during its regulatory review, such as the request we received from the FDA with respect to providing a minimum of24-month fracture data for approval of abaloparatide-SC. Delays in obtaining regulatory approvals may:•delay commercialization of, and our ability to derive product revenues from, our product candidates; •impose costly procedures on us; and •diminish any competitive advantages that we may otherwise enjoy. The abaloparatide-SC finished product is a drug/device combination product candidate with both a drug and device component and with the primary mode ofaction being provided by the investigational drug abaloparatide. Based on our discussions to date with the FDA, we believe that abaloparatide-SC will be regulatedas a combination product by the FDA, and both drug and device components will be required for review as part of our NDA submission. We expect that our NDAwould be submitted to the Center for Drug Evaluation and Research and be reviewed with support from the FDA Office of Combination Products and the FDACenter for Devices and Radiological Health for the device aspects of the abaloparatide-SC product candidate. In addition, there are device-related manufacturingand other regulatory requirements (e.g., current good manufacturing practices, or cGMPs, and adverse event reporting) to which we may be subject by virtue of theproduct's status as a drug/device combination product. As a result of these factors, we may experience delays in the product development and regulatory review andapproval process in seeking a drug/device combination product approval under an NDA. Even if we comply with all FDA requests, the FDA may ultimately reject one or more of our NDAs. We may never obtain regulatory approval forabaloparatide-SC, or any of our product candidates. Failure to obtain FDA approval of abaloparatide-SC, or any of our product candidates will severely undermineour business by leaving us without a saleable product, and therefore without any source of revenues, until another product candidate can be developed. There is noguarantee that we will ever be able to develop or acquire any product candidate. In foreign jurisdictions, we must receive approval from the appropriate regulatory authorities before we can commercialize any drugs. Foreign regulatoryapproval processes generally include all of the risks associated with the FDA approval procedures described above. We cannot assure you that we will receive theapprovals necessary to commercialize abaloparatide-SC, or any of our product candidates for sale outside the United States.39Table of ContentsAny collaboration arrangements that we may enter into in the future may not be successful, which could adversely affect our ability to develop andcommercialize abaloparatide-SC, or any of our other product candidates. Our product development programs and the potential commercialization of our product candidates will require substantial cash to fund expenses. For some ofour product candidates, we may decide to collaborate with pharmaceutical and biotechnology companies for the development and potential commercialization ofthose product candidates. We will face, to the extent that we decide to enter into collaboration agreements, significant competition in seeking appropriatecollaborators. Moreover, collaboration arrangements are complex and time consuming to negotiate, document and implement. We may not be successful in ourefforts to establish and implement collaborations or other alternative arrangements should we so chose to enter into such arrangements. The terms of any collaborations or other arrangements that we may establish may not be favorable to us. If that were to occur, we may have to curtail thedevelopment of a particular product candidate, reduce or delay its development program or one or more of our other development programs, delay its potentialcommercialization or reduce the scope of our sales or marketing activities, or increase our expenditures and undertake development or commercialization activitiesat our own expense. If we elect to increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additionalcapital, which may not be available to us on acceptable terms or at all. If we do not have sufficient funds, we will not be able to bring our product candidates tomarket and generate product revenue. Any future collaborations that we enter into may not be successful. The success of our collaboration arrangements will depend heavily on the efforts andactivities of our future collaborators. Collaborators generally have significant discretion in determining the efforts and resources that they will apply to thesecollaborations. If a collaborator fails to provide sufficient effort and resources to a development program, we may not realize the full potential or intended benefitof the collaboration, and the development program may be delayed or curtailed.Clinical trials are very expensive, time-consuming and difficult to design and implement. Human clinical trials are very expensive and difficult to design and implement, in part because they are subject to rigorous regulatory requirements. Asubstantial portion of our abaloparatide development costs is denominated in euros and any adverse movement in the dollar/euro exchange rate will result inincreased costs and require us to raise additional capital to complete the development of our products. The clinical trial process is also time consuming.Furthermore, failure can occur at any stage of the trials, and we could encounter problems that cause us to abandon or repeat clinical trials. The commencement andcompletion of clinical trials may be delayed by several factors, including:•changes in government regulation, administrative action or changes in FDA or foreign regulatory authority policy with respect to clinical trials thatchange the requirements for approval; •unforeseen safety issues; •determination of dosing issues; •lack of effectiveness during clinical trials; •slower than expected rates of patient recruitment and enrollment; •failure of sites to comply with requirements for conducting clinical trials; •inability to monitor patients adequately during or after treatment; and •inability or unwillingness of medical investigators to follow our clinical protocols.40Table of Contents In addition, we, the FDA, or other equivalent regulatory authorities and ethics committees with jurisdiction over our studies may suspend our clinical trials atany time if it appears that we are exposing participants to unacceptable health risks or if the FDA or foreign regulatory authorities find deficiencies in ourregulatory submissions or the conduct of these trials. Therefore, we cannot predict with any certainty the schedule for existing or future clinical trials. Any suchunexpected expenses or delays in our clinical trials could increase our need for additional capital, which may not be available on favorable terms or at all.Most of our investigational product candidates are in early stages of clinical trials. Except for abaloparatide-SC and abaloparatide-TD, each of our other product candidates (i.e., RAD1901 and RAD140) is in the early stages of developmentand requires extensive preclinical and clinical testing. We cannot predict with any certainty if or when we might submit an NDA or equivalent application toforeign regulatory authorities for regulatory approval for any of our product candidates or whether any such NDA or equivalent application would be accepted forfiling by the FDA or foreign regulatory authorities or approved if filed.The results of clinical trials may not support our product candidate claims. Even if our clinical trials are completed as planned, we cannot be certain that the results will support regulatory approval of our product candidates. Success inpreclinical testing and early clinical trials does not ensure that later clinical trials will be successful, and we cannot be sure that the results of later clinical trials willreplicate the results of prior clinical trials and preclinical testing. The clinical trial process may fail to demonstrate that our product candidates are safe for humansand effective for proposed uses. This failure would cause us to abandon a product candidate and may delay development of other product candidates. Any delay in,or termination of, our clinical trials will delay the submission of our NDAs to the FDA or equivalent application to foreign regulatory authorities and, ultimately,our ability to commercialize our product candidates and generate product revenues. In addition, our clinical trials to date (other than the ACTIVE Phase 3 ClinicalTrial for abaloparatide-SC) have involved small patient populations. Because of the small sample sizes, the results of these clinical trials may not be indicative offuture results. In addition, third parties could conduct clinical trials using the product candidates we license. We would have no control over how these trials are conductedand the results could potentially contradict the results we have obtained, or will obtain from the clinical trials we conduct.If serious adverse or undesirable side effects are identified during the development of our product candidates, we may need to abandon our development ofsome of our product candidates. Undesirable side effects caused by our product candidates could cause us, regulatory authorities, and/or ethics committees to interrupt, delay or halt clinicaltrials and could result in a more restrictive label or cause the delay or denial of regulatory approval by the FDA or other comparable foreign authorities. It isimpossible to predict when or if any of our product candidates will prove effective or safe in humans or will receive regulatory approval, if ever. If our productcandidates result in undesirable side effects or have characteristics that are unexpected, we may need to abandon their development. Drug-related side effects couldaffect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may harmour business, financial condition and prospects significantly. Additionally if one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by suchproducts, a number of potentially significant negative consequences could result, including:•regulatory authorities may withdraw approvals of such product;41Table of Contents•regulatory authorities may require additional warnings on the label; •we may be required to create a medication guide outlining the risks of such side effects for distribution to patients; •we could be sued and held liable for harm caused to patients; and •our reputation may suffer. Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantlyharm our business, results of operations and prospects.Any product candidate for which we obtain marketing approval could be subject to restrictions or withdrawal from the market and we may be subject topenalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, when and if any of them areapproved. Any product candidate for which we obtain marketing approval, along with the manufacturing processes, post-approval clinical data, labeling, advertising andpromotional activities for such product, will be subject to continual requirements of and review by the FDA and foreign regulatory authorities. These requirementsinclude submissions of safety and other post-marketing information and reports, registration and listing requirements, cGMP requirements relating to qualitycontrol, quality assurance and corresponding maintenance of records and documents, and requirements regarding the distribution of samples to physicians andrecordkeeping. Even if we obtain marketing approval of a product candidate, the approval may be subject to limitations on the indicated uses for which the productmay be marketed or to the conditions of approval, or contain requirements for costly post-marketing testing and surveillance to monitor the safety and/or efficacy ofthe product. The FDA closely regulates the post-approval marketing and promotion of drugs to ensure drugs are marketed only for the approved indications and inaccordance with the provisions of the approved labeling. The FDA imposes stringent restrictions on manufacturers' communications regarding off-label use and, ifwe market our products for other than their approved indications, we may be subject to enforcement action for off-label marketing. In addition, later discovery of previously unknown problems with our products, manufacturers or manufacturing processes, or failure to comply withregulatory requirements, may yield various results, including:•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 clinical trials; •warning or untitled letters; •withdrawal of the products from the market; •refusal to approve pending applications or supplements to approved applications that we submit; •voluntary or mandatory recall of products and related publicity requirements; •fines, restitution or disgorgement of profits or revenue; •suspension or withdrawal of marketing approvals; •refusal to permit the import or export of our products; •product seizure; or •injunctions or the imposition of civil or criminal penalties.42Table of Contents In addition, the FDA's policies may change and additional government regulations may be enacted that could prevent, limit, or delay regulatory approval ofour product candidates. We cannot predict the likelihood, nature, or extent of government regulation that may arise from future legislation or administrative action,either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if weare not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability,which would adversely affect our business.The commercial success of any product candidates that we may develop and that may be approved will depend upon the degree of market acceptance byregulators, key opinion leaders, physicians, patients, healthcare payors and others in the medical community. Even if the FDA or foreign regulatory authorities approves one or more of our product candidates, physicians and patients may not accept and use them.Acceptance and use of any of our products will depend upon a number of factors including:•perceptions by members of the healthcare community, including physicians and key opinion leaders, about the safety and effectiveness of our drug; •cost-effectiveness of our product relative to competing products; •availability of coverage and reimbursement for our product from government or other healthcare payors; and •effectiveness of marketing and distribution efforts by us and our licensees and distributors, if any. If any of our product candidates are commercialized and unexpected adverse events are reported in connection with the use of any of those products, physicianand patient acceptance of the product could deteriorate and the commercial success of such product could be adversely affected. We are required to report to theFDA or similar bodies in other countries events associated with our products relating to death or serious injury. Adverse events could result in additional regulatorycontrols, such as for the imposition of costly post-approval clinical studies or revisions to approved labeling which could limit the indications or patient populationfor a product or could even lead to the withdrawal of a product from the market. Because we expect sales of our current product candidates, if approved, to generatesubstantially all of our product revenues for the foreseeable future, the failure of these drugs to gain market acceptance or, once gained, a decrease in marketacceptance would harm our business and would require us to seek additional financing.Our ability to successfully commercialize products depends in part on the extent to which coverage and reimbursement for the costs of our products and relatedtreatments will be available in the United States and worldwide from government health administration authorities, private health insurers and otherorganizations. Our ability to commercialize our product candidates if approved, alone or with collaborators, will depend in large part on the extent to which coverage andreimbursement will be available post-approval from:•government and health administration authorities; •private health maintenance organizations and health insurers; and •other healthcare payors. In the United States and internationally, sales of products that we market in the future, and our ability to generate revenues on such sales, are dependent, insignificant part, on the availability and level of coverage and reimbursement from third party payors such as state and federal governments,43Table of Contentsmanaged care providers and private insurance plans. Private insurers, such as health maintenance organizations and managed care providers, have implementedcost cutting and reimbursement initiatives and likely will continue to do so in the future. These include establishing formularies that govern the drugs and biologicsthat will be offered and also the out of pocket obligations of member patients for such products. In addition, particularly in the United States and increasingly inother countries, we may be required to provide discounts and pay rebates to state and federal governments and agencies in connection with purchases of ourproducts that are reimbursed by such entities. It is possible that future legislation in the United States and other jurisdictions could be enacted which couldpotentially impact the reimbursement rates for the products we are developing and may develop in the future and also could further impact the levels of discountsand rebates paid to federal and state government entities. Any legislation that impacts these areas could impact, in a significant way, our ability to generaterevenues from sales of products that, if successfully developed, we bring to market. There is no legislation at the EU level governing the pricing and reimbursement of medicinal products in the EU. As a result, the competent authorities of eachof the 28 EU Member States have adopted individual strategies regulating the pricing and reimbursement of medicinal products in their territory. These strategiesoften vary widely in nature, scope and application. However, a major element that they have in common is an increased move towards reduction in thereimbursement price of medicinal products, a reduction in the number and type of products selected for reimbursement, and an increased preference for genericproducts over innovative products. These efforts have mostly been executed through these countries' existing price control methodologies. These efforts havemostly been executed through these countries' existing price-control methodologies, including price cuts, mandatory rebates, value-based pricing, and referencepricing (i.e., referencing prices in other countries and using those reference prices to set a price). The government of the UK announced the phase out of itsestablished Pharmaceutical Pricing Reimbursement Scheme approach in January 2014 and the adoption of a new value based pricing approach, at least for newproduct introductions. Under this approach, in a complete departure from established methodologies, reimbursement levels of each drug will be explicitly based onan assessment of value, looking at the benefits for the patient, unmet need, therapeutic innovation, and benefit to society as a whole. It is increasingly common inmany EU Member States for Marketing Authorization Holders to be required to demonstrate the pharmaco economic superiority of their products as compared toproducts already subject to pricing and reimbursement in specific countries. In order for drugs to be evaluated positively under such criteria, pharmaceuticalcompanies may need to re-examine, and consider altering, a number of traditional functions relating to the selection, study, and management of drugs, whethercurrently marketed, under development, or being evaluated as candidates for research and/or development. Future legislation, including the current versions being considered at the federal and state level in the United States and at the national level in EU MemberStates, or regulatory actions implementing recent or future legislation may have a significant effect on our business. If government and other healthcare payors donot provide adequate coverage and reimbursement levels for our product candidates, once approved, market acceptance of our products could be reduced. Inaddition, negotiating prices with government authorities under current and proposed legislation can delay the commercialization of our product candidates.We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that maybe more profitable or for which there is a greater likelihood of success. Because we have limited financial and managerial resources, we narrowly focus on research programs and product candidates that we identify for specificindications. As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greatercommercial potential. Our resource allocation decisions may cause us to fail to capitalize44Table of Contentson viable commercial products or profitable market opportunities. Our spending on current and future research and development programs and product candidatesfor specific indications may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particularproduct candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases in which itwould have been more advantageous for us to retain sole development and commercialization rights to such product candidate.If we experience delays in the enrollment of patients in our clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented. We may not be able to initiate or continue clinical trials for some of our product candidates if we are unable to locate and enroll a sufficient number of eligiblepatients to participate in these trials as required by the FDA or foreign regulatory authorities. In addition, many of our competitors have ongoing clinical trials forproduct candidates that could be competitive with our product candidates, and patients who would otherwise be eligible for our clinical trials may instead enroll inclinical trials of our competitors' product candidates. Enrollment delays in our clinical trials may result in increased development costs for our product candidates, which would cause the value of the company todecline and limit our ability to obtain additional financing. Our inability to enroll a sufficient number of patients for any of our current or future clinical trials wouldresult in significant delays or may require us to abandon one or more clinical trials altogether.Risks Related to Our Dependence on Third PartiesOur drug development programs depend upon third-party researchers, investigators and collaborators who are outside our control. We depend upon independent researchers, investigators and collaborators, to conduct our preclinical and clinical trials under agreements with us. These thirdparties are not our employees and we cannot control the amount or timing of resources that they devote to our programs. Nevertheless, we are responsible forensuring that each of our studies is conducted in accordance with the applicable protocol, legal, regulatory and scientific standards and requirements, and ourreliance on third parties does not relieve us of our regulatory responsibilities. We and our third party researchers, investigators and collaborators are required tocomply with good clinical practice, or GCP, requirements, which are regulations and guidelines enforced by the FDA, the Competent Authorities of the MemberStates of the European Economic Area, or EEA, and comparable foreign regulatory authorities for all of our products in clinical development. Regulatoryauthorities enforce these GCPs through periodic inspections of trial sponsors, principal investigators and trial sites. If we or any of our CROs fail to comply withapplicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA, EMA or other comparable foreign regulatory authoritiesmay require us to perform additional clinical trials before approving our marketing applications. We cannot assure you that upon inspection by a given regulatoryauthority, such regulatory authority will determine that any of our clinical trials complies with GCP regulations. In addition, our clinical trials must be conductedwith product produced under cGMP regulations. Our failure to comply with these regulations may require us to repeat clinical trials, which would delay theregulatory approval process. In addition, these third parties may not assign as great a priority to our programs or pursue them as diligently as we would if we wereundertaking such programs ourselves. If outside collaborators fail to devote sufficient time and resources to our drug-development programs, or if theirperformance is substandard, the approval of our FDA or foreign regulatory authority applications, if any, and our introduction of new drugs, if any, will be delayed.These collaborators may also have relationships with other commercial45Table of Contentsentities, some of whom may compete with us. If our collaborators assist competitors at our expense, our competitive position would be harmed.If a regulatory or governmental authority determines that a financial interest in the outcome of the Phase 3 study of abaloparatide-SC by any of the entitieswho managed our Phase 3 clinical trial affected the reliability of the data from the Phase 3 clinical trial, our ability to use the data for our planned regulatorysubmissions could be compromised, which could harm our business and the value of our common stock. The Phase 3 clinical trial and subsequent extension studies of abaloparatide-SC are being managed by Nordic Bioscience Clinical Development VII A/S, orNordic, at certain clinical sites operated by the Center for Clinical and Basic Research, or CCBR, a leading global CRO with extensive experience in globalosteoporosis registration studies. Nordic controls, and holds an ownership interest in, the local CCBR clinical sites. The clinical trial investigators are employees ofCCBR and may also hold an equity interest in the local CCBR clinical trials. In consideration of Nordic's management of our Phase 3 clinical trial and subsequent extension studies, we agreed to make various cash payments to Nordicdenominated in both euros and U.S. dollars over the course of the Phase 3 ACTIVE and ACTIVExtend clinical trials, or the ACTIVE Clinical Trials, equal to atotal of up to approximately €53.0 million ($57.5 million) and a total of up to approximately $4.4 million plus up to an additional $5.0 million in aggregateperformance incentive payments, payable in cash. We also agreed to sell shares of capital stock to Nordic that were exchanged in May 2011 for 6,443 shares of ourseries A-5 convertible preferred stock for proceeds of approximately $0.5 million. These shares of our series A-5 convertible preferred stock automaticallyconverted into 28,258 shares of our common stock upon the listing of our common stock on the NASDAQ Global Market. Pursuant to the terms of our agreementswith Nordic, we were required to issue to Nordic shares of stock with an aggregate value of up to approximately €44.3 million ($48.1 million) and $0.8 million inconsideration of Nordic's management of the ACTIVE Clinical Trials. These shares of stock accrued at a quarterly rate based on the progress of the ACTIVEClinical Trials and were issuable at a price per share equal to the greater of (1) the fair market value of our common stock as of the applicable accrual date or(2) $81.42 and rounding down the resulting quotient to the nearest whole number. On each of December 31, 2013 and March 31, 2014, our Board of Directorsdeclared a stock dividend to pay all shares of stock that had accrued as of such dates and that were anticipated to accrue through December 31, 2014, representingan aggregate of 682,958 shares of our Series A-6 convertible preferred stock that automatically converted into 2,995,453 shares of our common stock upon thelisting of our common stock on the NASDAQ Global Market. Following the completion of our initial public offering of shares of our common stock on June 11,2014, or our initial public offering, all compensation remaining payable to Nordic in consideration of their management of the ACTIVE Clinical Trials becamepayable in cash. The fair market value of our common stock may be subject to wide fluctuations in response to various factors, many of which are beyond our control.Accordingly, the shares of stock that we have issued to Nordic in consideration of Nordic's management of the ACTIVE Clinical Trials may be less than the fullvalue originally anticipated under our agreements with Nordic, assuming Nordic did not expect the fair market value of our stock to fluctuate widely over the termof such agreements. As a result, the total consideration that Nordic received in stock and will receive in cash may be viewed to be below the market price paid byother companies for comparable clinical trial services. Because of the potential decrease in the value of the common stock issued to Nordic if there was a negative outcome of the ACTIVE Clinical Trials, Nordic,CCBR and the clinical trial investigators may be viewed as having a financial interest in the outcome of the study. We have obtained written acknowledgmentsfrom the clinical trial investigators certifying that they have no financial interest in the outcome of the ACTIVE Clinical Trials. However, if the FDA, the EMA, orany other similar regulatory or governmental authority determines that Nordic, CCBR or the clinical trial investigators46Table of Contentshave a financial interest that affected the reliability of the data from the ACTIVE Clinical Trials, we could be subject to additional regulatory scrutiny and theutility of the ACTIVE Clinical Trials for purposes of our planned regulatory submissions could be compromised, which could have a material adverse effect on ourbusiness and the value of our common stock.We will rely exclusively on third parties to formulate and manufacture our product candidates. We have no experience in drug formulation or manufacturing and do not intend to establish our own manufacturing facilities. We lack the resources andexpertise to formulate or manufacture our own product candidates. We have entered into agreements with contract manufacturers to manufacture our productcandidates for use in clinical trial activities. These contract manufacturers are currently our only source for the production and formulation of our productcandidates. We may not have sufficient clinical supplies of our product candidates but believe that our contract manufacturers will be able to produce sufficientsupply of our product candidates to complete all of the planned clinical studies. If our contract manufacturers are unable to produce, in a timely manner, adequateclinical supplies to meet the needs of our clinical studies, we would be required to seek new contract manufacturers that may require us to modify our finishedproduct formulation and modify or terminate our clinical studies. Any modification of our finished product or modification or termination of our clinical studiescould adversely affect our ability to obtain necessary regulatory approvals and significantly delay or prevent the commercial launch of the product if it were to beapproved, which would materially harm our business and impair our ability to raise capital. In addition, the facilities and processes and controls used by ourcontract manufacturers to manufacture our product candidates must be approved by the EMA, and by the FDA pursuant to inspections that will be conducted afterwe submit our NDA. We do not control the facilities or manufacturing process, and are completely dependent on, our contract manufacturing partners forcompliance with cGMPs for manufacture of both active drug substances and finished drug products. If our contract manufacturers cannot successfully manufacturematerial that conforms to our specifications and the strict regulatory requirements of the FDA or other regulatory authorities, they will not be able to secure and/ormaintain regulatory approval for their manufacturing facilities. In addition, we have no control over the ability of our contract manufacturers to maintain adequatequality control, quality assurance and qualified personnel. If the FDA or a comparable foreign regulatory authority does not approve our contract manufacturers forthe manufacture of our product candidates or if they withdraw any such approval in the future, we may need to find alternative manufacturing facilities, whichwould significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved. We depend on a number of single source contract manufacturers to supply key components of abaloparatide. For example, we depend on Lonza Group Ltd., orLonza, which produces supplies of bulk drug product of abaloparatide to support the abaloparatide-SC and abaloparatide-TD clinical studies and any potentialcommercial launch. We also depend on Vetter Pharma Fertigung GmbH & Co, or Vetter, and Ypsomed AG, or Ypsomed, for the production of finished supplies ofabaloparatide-SC and we depend on 3M Co. and 3M Innovative Properties Co., or, together 3M, for the production of abaloparatide-TD. Because of ourdependence on Vetter for the "fill and finish" part of the manufacturing process for abaloparatide-SC, we are subject to the risk that Vetter may not have thecapacity from time to time to produce sufficient quantities of abaloparatide to meet the needs of our clinical studies or be able to scale to commercial production ofabaloparatide. While we are currently in discussions, to date, we have not entered into a long-term agreement with any of Lonza, Vetter or Ypsomed, each of whomcurrently produces abaloparatide or related components on a purchase order basis for us. Accordingly, Lonza, Vetter and Ypsomed could terminate theirrelationship with us at any time and for any reason. We may not be able to negotiate long-term agreements on acceptable terms, or at all. If our relationship withany of these contract manufacturers is terminated, or if they are unable to produce abaloparatide or related components in required quantities, on a timely basis or atall, or if we are forced to accept unfavorable terms for our future relationship, our47Table of Contentsbusiness and financial condition would be materially harmed. Because the manufacturing process for abaloparatide-TD requires the use of 3M's proprietarytechnology, 3M is our sole source for finished clinical trial supplies of abaloparatide-TD. To date, we have not entered into a commercial supply agreement with3M. If we were not able to negotiate commercial supply terms with 3M, as we depend on 3M for production of abaloparatide-TD, we would be unable tocommercialize this product if it were to be approved. Or, if we are forced to accept unfavorable terms for our future relationship with 3M, our business andfinancial condition would be materially harmed. If any of our current product candidates or any product candidates we may develop or acquire in the future receiveFDA or foreign regulatory authority approval, we will rely on one or more third-party contractors to manufacture our drugs or related components. Our anticipatedfuture reliance on a limited number of third-party manufacturers exposes us to the following risks:•We may be unable to identify manufacturers on acceptable terms, or at all, because the number of potential manufacturers is limited and the FDAmust approve any replacement contractor. This approval would require new testing and compliance inspections. In addition, a new manufacturerwould have to be educated in, or develop substantially equivalent processes for, production of our products after receipt of FDA approval, if any. •Our third-party manufacturers might be unable to formulate and manufacture our drugs or related components in the volume and of the qualityrequired to meet our clinical needs and commercial needs, if any. •Our contract manufacturers may not perform as agreed or may not remain in the contract manufacturing business for the time required to supply ourclinical trials or to successfully produce, store and distribute our products. •Drug manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies to ensure strictcompliance with cGMP, and other government regulations and corresponding foreign standards, and failure to comply with cGMP or correspondingforeign standards can result in compliance actions that may limit a manufacturer's production or prohibit a manufacturer from producing some or allproducts at a facility and/or importing it into the United States or a foreign country. We do not have control over third-party manufacturers'compliance with these regulations and standards. •If any third-party manufacturer makes improvements in the manufacturing process for our products, any such improvement(s) could be subject toFDA review and prior approval, and we may not own, or may have to share, the intellectual property rights to the innovation. Each of these risks could delay our clinical trials, the approval, if any, of our product candidates by the FDA or foreign regulatory authorities or thecommercialization of our product candidates or result in higher costs or deprive us of potential product revenues.If we fail to establish an effective distribution process utilizing cold chain logistics for abaloparatide-SC, our business may be adversely affected. We do not currently have the infrastructure necessary for distributing pharmaceutical products to patients. We will be contracting with a third-party logisticscompany to warehouse abaloparatide-SC and distribute it to specialty pharmacies and wholesale distributors who will supply abaloparatide-SC to the market. Wewill require that abaloparatide-SC be maintained at a controlled refrigerated temperature throughout the distribution chain. This distribution chain will requiresignificant coordination among our manufacturing, supply-chain and finance teams, as well as commercial departments, including market access, sales, andmarketing. In addition, failure to secure contracts with appropriate pharmacy providers and/or wholesale distributors could negatively impact the distribution ofabaloparatide-SC, and failure to coordinate financial systems could negatively impact our ability to accurately report48Table of Contentsproduct revenue. If we are unable to effectively establish and manage the distribution process, the commercial launch and sales of abaloparatide-SC will be delayedor severely compromised and our results of operations may be harmed.Risks Related to Marketing and Sale of Our ProductsWe currently have limited commercial and medical affairs capabilities and have no experience selling, marketing or distributing products. If we are unable tobuild these capabilities on our own or through partnerships or collaborations, we may not be able to successfully commercialize abaloparatide-SC, if approved,or any future product candidates or generate product revenue. We currently have limited commercial and medical affairs capabilities and no sales capabilities, and we have no experience commercializing a pharmaceuticalproduct. We intend to build an internal sales force to market and sell our products to specialists within the target indications, if approved, and also to pursuecollaborative arrangements to market and sell our products within the target indications if approved. Therefore, our future success depends, in part, on our ability toenter into and maintain collaborative relationships for such capabilities, the collaborators' strategic interest in the products under development and suchcollaborators' ability to successfully market and sell any such products. In addition, our ability to build effective commercial, medical affairs, marketing, sales, market access, managerial and other non-technical capabilities willdepend on a number of factors, including our ability to:•identify, recruit, hire, train, incentivize and retain a significant number of commercial and medical affairs personnel, including a specialty salesforce with appropriate technical expertise; •train our sales representatives, who will have no prior experience with our company or abaloparatide-SC, to deliver clear and compelling messageswithin the scope of the approved labeling regarding abaloparatide-SC and to be credible and persuasive in educating physicians on the appropriatesituations to consider prescribing it as set forth in the approved labeling; •ensure our commercial customer-facing team, including sales, market access, and field logistics professionals, effectively build relationships withtheir respective customers; •manage a geographically dispersed national commercial customer-facing organization; and •manage our significant projected growth and the integration of new personnel. Building our commercial and medical affairs capabilities may be more expensive and time consuming than we anticipate, requiring us to divert resources fromother intended purposes or preventing us from building these capabilities to the desired levels. Any failure or delay in building these capabilities on our own orthrough partnerships or collaborations will adversely impact the successful commercialization of abaloparatide-SC, or any future product candidate. If we establisha partnership or collaboration for purposes of commercializing abaloparatide-SC, or any future product candidate, the launch of that product candidate would needto be established in conjunction with our partner, which could result in a change in timing of the commercial launch. In addition, given our lack of prior experience in marketing, selling and distributing pharmaceutical products, our initial specialty sales force may bematerially smaller than the actual number of sales representatives required to successfully commercialize abaloparatide-SC. As such, we may be required to hiresubstantially more sales representatives to adequately support the commercialization of abaloparatide-SC.49Table of ContentsIf we cannot compete successfully for market share against other drug companies, we may not achieve sufficient product revenues and our business will suffer. The market for our product candidates is characterized by intense competition and rapid technological advances. If any of our product candidates receivesFDA or foreign regulatory authority approval, it will compete with a number of existing and future drugs and therapies developed, manufactured and marketed byothers. Existing or future competing products may provide greater therapeutic convenience or clinical or other benefits for a specific indication than our products,or may offer comparable performance at a lower cost. If our products fail to capture and maintain market share, we may not achieve sufficient product revenues andour business will suffer. We are seeking regulatory approval of abaloparatide-SC for the treatment of osteoporosis in postmenopausal women. We expect to compete against well-known treatment options, including Lilly's Forteo. In addition, there are other organizations working to develop new therapies to treat osteoporosis. In April 2012,UCB and Amgen started a Phase 3 clinical trial program for their anti-sclerostin antibody for the treatment of osteoporosis. In addition, there is at least onebiosimilar to Lilly's Forteo under review by the EMA which, if approved, could exert pricing pressure on the anabolic class in which abaloparatide-SC wouldcompete. In order to compete successfully in this market, we will have to demonstrate to physician and payors that the treatment of osteoporosis withabaloparatide-SC is worthwhile and is a better alternative to existing or new therapies. We face significant competition from many fully integrated pharmaceutical companies and smaller companies that are collaborating with largerpharmaceutical companies, academic institutions, government agencies and other public and private research organizations. Many of these competitors havecompounds already approved or in development. In addition, many of these competitors, either alone or together with their collaborative partners, operate largerresearch and development programs or have substantially greater financial resources than we do, as well as significantly greater experience in:•developing drugs; •undertaking preclinical testing and human clinical trials; •obtaining FDA and other regulatory approvals of drugs; •formulating and manufacturing drugs; and •launching, marketing and selling drugs.Developments by competitors may render our products or technologies obsolete or non-competitive. The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change. Some of the drugs thatwe are attempting to develop, such as our investigational product candidates abaloparatide-SC, abaloparatide-TD, RAD1901 and RAD140, will have to competeagainst existing therapies if they are approved. In addition, a large number of companies are pursuing the development of pharmaceuticals that target the samediseases and conditions that we are targeting. We face competition from pharmaceutical and biotechnology companies in the United States and abroad. In addition,companies doing business in different but related fields represent substantial competition. Many of these organizations competing with us have substantially greatercapital resources, larger research and development staffs and facilities, longer drug development history in obtaining regulatory approvals, and greatermanufacturing and marketing capabilities than we do. These organizations also compete with us to attract qualified personnel and parties for acquisitions, jointventures or other collaborations, and therefore, we may not be able to hire or retain qualified personnel to run all facets of our business. These risks could renderour products or technologies obsolete or non-competitive.50Table of ContentsWe may incur substantial liabilities and may be required to limit commercialization of our products in response to product liability lawsuits. The testing and marketing of medical products entail an inherent risk of product liability. Even if one of our investigational product candidates is approved bythe FDA or foreign regulatory authorities, if we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or berequired to limit commercialization of our products. Our inability to obtain sufficient product liability insurance at an acceptable cost to protect against potentialproduct liability claims could prevent or inhibit the commercialization of pharmaceutical products we develop, alone or with collaborators.Risks Related to Our Intellectual PropertyIf we fail to comply with our obligations in our intellectual property licenses with third parties, we could lose license rights that are important to our business. We are a party to a number of intellectual property license agreements with third parties and expect to enter into additional license agreements in the future.Our existing license agreements impose, and we expect that any future license agreements will impose, various diligence, milestone payment, royalty, insuranceand other obligations on us. If we fail to comply with these obligations, our licensors may have the right to terminate these agreements, in which event we mightnot be able to develop and market any product that is covered by these agreements. Termination of these licenses or reduction or elimination of our licensed rightsmay result in our having to negotiate new or reinstated licenses with less favorable terms. The occurrence of such events could materially harm our business.If our efforts to protect our intellectual property related to abaloparatide-SC, abaloparatide-TD, RAD1901 and/or RAD140 fail to adequately protect theseassets or if we are unable to secure all necessary intellectual property, we may lose the ability to license or successfully commercialize one or more of thesecandidates. Our commercial success is significantly dependent on intellectual property related to our portfolio of product candidates. We are either the licensee or assigneeof numerous issued and pending patent applications that cover various aspects of our assets, including abaloparatide-SC, abaloparatide-TD, RAD1901 andRAD140. Patents covering abaloparatide as a composition of matter have been issued in the United States (US Patent No. 5,969,095) and several additional countries.Because the abaloparatide composition of matter patent was filed in 1996, it is expected to have an expiration in 2016 in the United States, and additional countrieswhere it has issued. European Patent No. 0847278, which was included in the license from Ipsen Pharma SAS, or Ipsen, and claimed the composition of matter ofabaloparatide, lapsed due to Ipsen's failure to pay annuities. We are pursuing restoration of those patent rights. To date, the patent rights in Austria, Belgium,Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Sweden and the United Kingdom have been restored. As a result of the lapseof patent rights, we believe that some of Ipsen's rights under our license agreement with Ipsen have terminated. We are in discussions with Ipsen regarding theseIpsen rights and related terms of our license agreement. If we fail to reach agreement, we or Ipsen may determine to pursue available remedies, including formaldispute resolution. We believe that the data and market exclusivity provided in Europe for a new chemical entity, coupled with the need for a potential competitorto conduct clinical trials, will likely provide a longer barrier to entry than the patent protection provided by the original European patent term, which will expire in2016. We and Ipsen are also co-assignees to US Patent No. 7,803,770 that we believe provides exclusivity until October 3, 2027 and may be extended to March 26,2028 in the United States (not including any Hatch-Waxman patent term extension) for the method of treating osteoporosis with the intended therapeutic dose forabaloparatide-SC.51Table of Contents We and Ipsen are also co-assignees to US Patent No. 8,148,333 that we believe provides exclusivity until 2027 in the United States (not including any Hatch-Waxman patent term extension) for the intended therapeutic formulation for abaloparatide-SC. We and 3M are co-assignees to several foreign and corresponding U.S. patent applications with the earliest priority date of April 22, 2011, which covervarious aspects of abaloparatide for microneedle application. Any issued patents resulting from these applications will expire in 2032. However, pending patentapplications in the United States and elsewhere may not issue since the interpretation of the legal requirements of patentability in view of claimed inventions arenot always predictable. Additional intellectual property covering abaloparatide-TD technology exists in the form of proprietary information protected as tradesecrets. These can be accidentally disclosed to, independently derived by or misappropriated by competitors, possibly reducing or eliminating the exclusivityadvantages of this form of intellectual property, thereby allowing those competitors more rapid entry into the marketplace with a competitive product, whichreduces our advantage with abaloparatide-TD. In addition, trade secrets may in some instances become publicly available through required disclosures in regulatoryfiles. Alternatively, competitors may sometimes reverse engineer a product once it becomes available on the market. Even where a competitor does not use anidentical technology for the delivery of abaloparatide, it is possible that they could achieve an equivalent or even superior result using another technology. Suchoccurrences could lead to either one or more alternative competitor products becoming available on the market and/or one or more generic competitor products onthe market gaining market share and causing a corresponding decrease in market share and/or price for abaloparatide-TD even if it were to be successfullydeveloped and approved by the FDA. Patents covering RAD1901 as a composition of matter, as well as the use of RAD1901 for the treatment of estrogen-dependent breast cancer, have been issuedin the United States, Canada, Australia, Japan and Europe, and are pending in India. The RAD1901 composition of matter patents in the United States expire in2023 and may be extended to 2026 (not including any Hatch-Waxman patent term extension). One patent has been issued in the United States (US PatentNo. 8,933,130) for treating vasomotor disturbances or hot flashes on January 13, 2015 (statutory term expires on June 22, 2027, and may be extended toOctober 19, 2031 with 1,580 days of patent term adjustment due to delays in patent prosecution by the USPTO). Additional patent applications relating to methodsof treating vasomotor symptoms and clinical dosage strengths using RAD1901 have been filed. Pending patent applications in the United States and elsewhere maynot issue since the interpretation of the legal requirements of patentability in view of any claimed invention before a patent office are not always predictable. As aresult, we could encounter challenges or difficulties in building, maintaining and/or defending our intellectual property both in the United States and abroad. Patent applications covering RAD140 and other selective androgen receptor modulator compounds have been granted in the United States, Europe, Canada,Mexico, Japan and Australia, and are pending in Brazil and India. The RAD140 composition of matter patents expire in 2029 in the United States (not includingany Hatch-Waxman patent term extension) and additional countries if and when they issue. Since patents are technical legal documents that are frequently subject to intense litigation pressure, there is risk that even if one or more patents related to ourproducts does issue and is asserted that the patent(s) will be found invalid, unenforceable and/or not infringed when subject to said litigation. Finally, theintellectual property laws and practices can vary considerably from one country to another and also can change with time. As a result, we could encounterchallenges or difficulties in building, maintaining and defending our intellectual property both in the United States and abroad.52Table of Contents We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to patents issued orlicensed to us, including interference proceedings before the USPTO. Third parties also may assert infringement claims against us. If we are found to infringe athird party's intellectual property rights, we could be required to obtain a license from such third party to continue developing and marketing our products andtechnology. However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, itcould be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to ceasecommercializing the infringing technology or product. In addition, we could be found liable for monetary damages. A finding of infringement could prevent usfrom commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business. Claims that we havemisappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business. For example, we are aware of aprovisional patent application filed with the USPTO that could be relevant to the use of RAD1901 to treat indications for which we are developing RAD1901. If apatent issues from this patent application with claims covering the use of RAD1901 to treat indications for which we are developing RAD1901, we may need tolicense the patent in order to commercialize RAD1901 specifically for the treatment of such indications even if RAD1901 were successfully developed andapproved. We cannot assure you that we will be able to secure a license on reasonable terms, if at all. If we need a license of such patent in order to commercializeRAD1901 and are unable to secure one on reasonable terms, our business would be materially harmed.If 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, our competitors could develop and commercialize technology and products similar oridentical to ours, and our ability to successfully commercialize our technology and products may be adversely affected. 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 with respectto our proprietary technology and products. In some circumstances, we may not have the right to control the preparation, filing and prosecution of patentapplications, or to maintain the patents, covering technology or products that we license from third parties. Therefore, we cannot be certain that these patents andapplications will be prosecuted and enforced in a manner consistent with the best interests of our business. In addition, if third parties who license patents to us failto maintain these patents, or lose rights to those patents, the rights we have licensed may be 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 rightsare highly uncertain. Our and our licensors' pending and future patent applications may not result in patents being issued that protect our technology or products orthat effectively prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent laws inthe United States and other countries may diminish the value of our patents or narrow the scope of our patent protection. The laws of foreign countries may notprotect our rights to the same extent as the laws of the United States. Assuming the other requirements for patentability are met, in the United States, prior toMarch 16, 2013, the first to make the claimed invention was entitled to the patent, or a "first-to-invent" system, while outside the United States, the first to file apatent application is entitled to the patent, or a "first-to-file" system. With the implementation of the Leahy-Smith America Invents Act, the United States now has afirst-to-file system for patent applications filed on or after March 16, 2013. We may become involved in opposition, interference or derivation proceedingschallenging our patent rights or the patent rights of others. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent53Table of Contentsapplications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot becertain that we or our licensors were the first to make the inventions claimed in our owned and licensed patents or pending patent applications, or that we or ourlicensors were the first to file for patent protection of such inventions. An adverse determination in any such proceeding could reduce the scope of, or invalidate ourpatent rights, allow third parties to commercialize our technology or products and compete directly with us, without payment to us, or result in our inability tomanufacture or commercialize products without infringing third-party patent rights. 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 or licensedpatents by developing similar or alternative technologies or products in a non-infringing manner. The issuance of a patent is not conclusive as to its scope, validityor enforceability, and our owned and licensed patents may be challenged in the courts or patent offices in the United States and abroad. Any challenges may resultin patent claims being narrowed, invalidated or held unenforceable, which could limit our ability to stop or prevent us from stopping others from using orcommercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products. Given the amount oftime required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly aftersuch candidates are approved or commercialized. As a result, our owned and licensed patents may not provide us with sufficient rights to exclude others fromcommercializing products similar or identical to ours.Payments, fees, submissions and various additional requirements must be met in order for pending patent applications to advance in prosecution and issuedpatents to be maintained. Rigorous compliance with these requirements is essential to procurement and maintenance of patents integral to our productportfolio. Periodic maintenance fees, renewal fees, annuity fees and various other governmental fees on patents and/or patent applications will come due for paymentperiodically throughout the lifecycle of patent applications and issued patents. In order to help ensure that we comply with any required fee payment, documentaryand/or procedural requirements as they might relate to any patents for which we are an assignee or co-assignee, we employ competent legal help and relatedprofessionals as needed to comply with those requirements. Our outside patent counsel uses Computer Packages, Inc. for patent annuity payments. We depend onEisai and/or Ipsen to comply with any required fee payment, documentary and/or procedural requirements as they might relate to any patents we have licensed fromthem. Failure to meet a required fee payment, document production or procedural requirement can result in the abandonment of a pending patent application or thelapse of an issued patent. In some instances the defect can be cured through late compliance but there are situations where the failure to meet the required eventcannot be cured. Any failures could compromise the intellectual property protection around our preclinical or clinical candidates and possibly weaken or eliminateour ability to protect our eventual market share for that product.If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed. In addition to our patented technology and products, we rely on trade secrets, including unpatented know-how, technology and other proprietary information,to maintain our competitive position. We seek to protect these trade secrets, in part, by entering into non-disclosure and confidentiality agreements with parties thathave access to our trade secrets, such as our corporate collaborators, outside scientific collaborators, sponsored researchers, contract manufacturers, consultants,advisors and other third parties. We also enter into confidentiality and invention or patent54Table of Contentsassignment agreements with our employees and consultants. However, any of these parties may breach the agreements and disclose our proprietary information,and we may not be able to obtain adequate remedies for any breaches. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult,expensive and time-consuming, and the outcome is unpredictable. In addition, some courts inside and outside the United States are less willing or unwilling toprotect trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent themfrom using that technology or information to compete with us. If any of our trade secrets were to be disclosed to, or independently developed by a competitor, ourcompetitive position would be harmed.If we infringe the rights of third parties, we could be prevented from selling products and could be forced to pay damages and defend against litigation. If our products, methods, processes and other technologies infringe the proprietary rights of other parties, we could incur substantial costs and may have to:•obtain licenses, which may not be available on commercially reasonable terms, if at all; •abandon an infringing drug candidate; •redesign our products or processes to avoid infringement; •stop using the subject matter claimed in the patents held by others; •pay damages; or •defend litigation or administrative proceedings which may be costly whether we win or lose, which could result in a substantial diversion of ourfinancial and management resources.We may become involved in lawsuits to protect or enforce our patents, which could be expensive, time consuming and unsuccessful. Competitors may infringe our patents. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensiveand time consuming. In addition, in an infringement proceeding, a court may decide that a patent of ours is invalid and/or unenforceable, or may refuse to stop theother party from using the technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in any litigationproceeding could put one or more of our patents at risk of being invalidated and/or interpreted narrowly. Furthermore, because of the substantial amount ofdiscovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosureduring this type of litigation. In addition, our licensors may have rights to file and prosecute these types of claims, and we may be reliant on them to do so.We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers. Some of our employees were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potentialcompetitors. 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 be subject toclaims that we or these employees have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employee'sformer employer. Litigation may be necessary to defend against these claims. If we fail in defending any such claims, in addition to paying monetary damages, wemay lose valuable intellectual property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costsand be a distraction to management.55Table of ContentsIntellectual 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, and coulddistract our technical and management personnel from their normal responsibilities, delaying the development of our product candidates. In addition, there could bepublic announcements of the results of hearings, motions or other interim proceedings or developments, and if securities analysts or investors perceive these resultsto be negative, it could have a substantial adverse effect on the price of our common stock. Litigation or other proceedings could substantially increase ouroperating losses and reduce our resources available for development activities. We may not have sufficient financial or other resources to adequately conduct anylitigation or proceedings. Some of our competitors may be able to sustain the costs of any litigation or proceedings more effectively than we can because of theirsubstantially greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a materialadverse effect on our ability to compete in the marketplace.Risks Related to Legislation and Administrative ActionsHealthcare reform may have a material adverse effect on our industry and our results of operations. From time to time, legislation is implemented to reign in rising healthcare expenditures. In March 2010, President Obama signed into law the PatientProtection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or ACA. ACA includes a number of provisions affecting thepharmaceutical industry, including annual, non-deductible fees on any entity that manufactures or imports some types of branded prescription drugs and biologicsand increases in Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program. In addition, among other things, ACA also establishes a newPatient-Centered Outcomes Research Institute to oversee, identify priorities and conduct comparative clinical effectiveness research. In addition, other legislativechanges have been proposed and adopted since ACA was enacted, which also may impact our business. On August 2, 2011, the President signed into law theBudget Control Act of 2011, or BCA, which, among other things, created the Joint Select Committee on Deficit Reduction to recommend proposals in spendingreductions to Congress. The Joint Select Committee did not achieve its targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, triggeringthe legislation's automatic reduction to several government programs. These reductions include aggregate reductions to Medicare payments to providers of 2% perfiscal year, which went into effect on April 1, 2013 and, due to subsequent legislative amendments, will remain in effect through 2025 unless additionalCongressional action is taken. On January 2, 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, or ATRA, which among otherthings, further reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers. The full impact on our businessof these new laws is uncertain. We cannot predict whether other legislative changes will be adopted, if any, or how such changes would affect the pharmaceuticalindustry generally or our business in particular.We are subject to healthcare laws, regulation and enforcement, and our failure to comply with those laws could have a material adverse effect on our results ofoperations and financial conditions. We are subject to several healthcare regulations and enforcement by the federal government and the states and foreign governments in which we conduct ourbusiness. The laws that may affect our ability to operate include:•the federal Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic andClinical Health Act, which governs the56Table of Contentsconduct of various electronic healthcare transactions and protects the security and privacy of protected health information;•the federal healthcare programs' Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting,receiving, offering or paying remuneration, directly or indirectly, in exchange for or to induce either the referral of an individual for, or thepurchase, order or recommendation of, any good or service for which payment may be made under federal healthcare programs such as theMedicare and Medicaid programs. A person or entity does not need to have actual knowledge of the federal Anti-Kickback Statute or specific intentto violate it to have committed a violation; in addition, the government may assert that a claim including items or services resulting from a violationof the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act; •federal false claims laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claimsfor payment from Medicare, Medicaid, or other third-party payers that are false or fraudulent; •federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcarematters. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the federal Anti-KickbackStatute or specific intent to violate it to have committed a violation; •the federal Physician Payment Sunshine Act, or the Sunshine Act, requires applicable manufacturers of covered drugs to report payments and othertransfers of value to physicians and teaching hospitals, and ownership and investment interests held by physicians and their immediate familymembers. Manufacturers are required to submit reports to the government by the 90th day of each calendar year; and •state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or servicesreimbursed by any third-party payer, including commercial insurers; state laws that require pharmaceutical companies to comply with the industry'svoluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government or otherwise restrict payments thatmay be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related topayments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacyand security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the sameeffect, thus complicating compliance efforts. Our operations and future commercial activities in connection with any product candidate that is approved will be subject to comprehensive complianceobligations under state and federal fraud and abuse, false claims, physician payment transparency laws and government pricing regulations, as described above. Ifwe are found to be in violation of these regulations, we may be subject to penalties, including civil and criminal penalties, damages, fines, the curtailment orrestructuring of our operations, the exclusion from participation in federal and state healthcare programs and imprisonment, any of which could adversely affect ourability to operate our business and our financial results.We may be exposed to liability claims associated with the use of hazardous materials and chemicals. Our research and development activities may involve the controlled use of hazardous materials and chemicals. Although we believe that our safety proceduresfor using, storing, handling and disposing of these materials comply with federal, state and local laws and regulations, we cannot completely eliminate the risk ofaccidental injury or contamination from these materials. In the event of such an accident, we could be held liable for any resulting damages and any liability couldmaterially adversely57Table of Contentsaffect our business, financial condition and results of operations. In addition, the federal, state and local laws and regulations governing the use, manufacture,storage, handling and disposal of hazardous or radioactive materials and waste products may require us to incur substantial compliance costs that could materiallyadversely affect our business, financial condition and results of operations.Risks Related to Employee Matters and Managing GrowthAs we evolve from a company primarily involved in drug discovery and development into one that is also involved in the commercialization of pharmaceuticalproducts, we may have difficulty managing our growth and expanding our operations successfully. Our success will depend upon the expansion of our operations and the effective management of our growth, and if we are unable to manage this growtheffectively, our business will be harmed. As we advance our product candidates through the development process, we will need to expand our development,regulatory, manufacturing, quality, distribution, sales and marketing capabilities or contract with other organizations to provide these capabilities for us. As ouroperations expand, we expect that we will need to manage additional relationships with various collaborators, suppliers and other organizations. Our ability tomanage our operations and growth requires us to continue to improve our operational, financial and management controls, reporting systems and procedures. Forexample, some jurisdictions, such as the District of Columbia, have imposed licensing requirements for sales representatives. In addition, the District of Columbiaand the Commonwealth of Massachusetts, as well as the federal government by way of the Sunshine Act, have established reporting requirements that wouldrequire public reporting of compensation and other "transfers of value" paid to health care professionals and teaching hospitals, as well as ownership andinvestment interests held by such professionals and their immediate family members. Because the reporting requirements vary in each jurisdiction, compliance willbe complex and expensive and may create barriers to entering the commercialization phase. The need to build new systems as part of our growth could place astrain on our administrative and operational infrastructure. We may not be able to make improvements to our management information and control systems in anefficient or timely manner and may discover deficiencies in existing systems and controls. Such requirements may also impact our opportunities to collaborate withphysicians at academic research centers as new restrictions on academic-industry relationships are put in place. In the past, collaborations between academia andindustry have led to important new innovations, but the new laws may have an effect on these activities. While we cannot predict whether any legislative orregulatory changes will have negative or positive effects, they could have a material adverse effect on our business, financial condition and potential profitability.We may enter into or seek to enter into business combinations and acquisitions which may be difficult to integrate, disrupt our business, divert managementattention or dilute stockholder value. We may enter into business combinations and acquisitions. We have limited experience in making acquisitions, which are typically accompanied by a numberof risks, including:•the difficulty of integrating the operations and personnel of the acquired companies; •the potential disruption of our ongoing business and distraction of management; •the potential for unknown liabilities and expenses; •the failure to achieve the expected benefits of the combination or acquisition; •the maintenance of acceptable standards, controls, procedures and policies; and •the impairment of relationships with employees as a result of any integration of new management and other personnel.58Table of Contents If we are not successful in completing acquisitions that we may pursue in the future, we would be required to reevaluate our business strategy and we mayhave incurred substantial expenses and devoted significant management time and resources in seeking to complete the acquisitions. In addition, we could usesubstantial portions of our available cash as all or a portion of the purchase price, or we could issue additional securities as consideration for these acquisitions,which could cause our stockholders to suffer significant dilution.We rely on key executive officers and scientific and medical advisors, and their knowledge of our business and technical expertise would be difficult to replace. We are highly dependent on our chief executive officer and our principal scientific, regulatory and medical advisors. We do not have "key person" lifeinsurance policies for any of our officers. The loss of the technical knowledge and management and industry expertise of any of our key personnel could result indelays in product development, loss of customers and sales and diversion of management resources, which could adversely affect our operating results.If we are unable to hire additional qualified personnel, our ability to grow our business may be harmed. We will need to hire additional qualified personnel with expertise in preclinical testing, clinical research and testing, government regulation, formulation andmanufacturing and sales and marketing. We compete for qualified individuals with numerous biopharmaceutical companies, universities and other researchinstitutions. Competition for such individuals is intense, and we cannot be certain that our search for such personnel will be successful. Attracting and retainingqualified personnel will be critical to our success.Significant disruptions of information technology systems or breaches of data security could adversely affect our business. Our business is increasingly dependent on critical, complex and interdependent information technology systems to support business processes as well asinternal and external communications. Our computer systems are vulnerable to breakdown, malicious intrusion and computer viruses. Any failure to protect againstbreakdowns, malicious intrusions and computer viruses may result in the impairment of production and key business processes. In addition, our systems arepotentially vulnerable to data security breaches, whether by employees or others, which may expose sensitive data to unauthorized persons. Such data securitybreaches could lead to the loss of trade secrets or other intellectual property, or could lead to the public exposure of personal information of our employees, clinicaltrial patients, customers, and others. Such disruptions and breaches of security could expose us to liability and have a material adverse effect on the operatingresults and financial condition of our business.Risks Relating to Our SecuritiesOur stock price may be volatile, and the value of an investment in our common stock may decline. The trading price of our common stock may be subject to wide fluctuations in response to various factors, some of which are beyond our control, including:•results of clinical trials of our product candidates or those of our competitors; •our operating performance and the operating performance of similar companies; •the success of competitive products; •the overall performance of the equity markets; •the number of shares of our common stock publicly owned and available for trading;59Table of Contents•threatened or actual litigation; •changes in laws or regulations relating to our products, including changes in the structure of healthcare payment systems; •any major change in our board of directors or management; •publication of research reports about us or our industry or positive or negative recommendations or withdrawal of research coverage by securitiesanalysts; •large volumes of sales of our shares of common stock by existing stockholders; •general political, economic and market conditions; and •the other factors described in this "Risk Factors" section. In addition, the stock market in general has experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to theoperating performance of the companies whose shares trade in the stock market. Securities class action litigation has often been instituted against companiesfollowing periods of volatility in the overall market and in the market price of a company's securities. Such litigation, if instituted against us, could result in verysubstantial costs, divert our management's attention and resources and harm our business, operating results and financial condition.Because we do not anticipate paying any cash dividends on our common stock in the foreseeable future, capital appreciation, if any, will be your sole source ofgain. 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 growth anddevelopment of our business. As a result, capital appreciation, if any, of our common stock will be your sole source of gain for the foreseeable future.We have incurred and will continue to incur increased costs as a result of operating as a public company, and our management is required to devotesubstantial time to compliance initiatives. As a public company listed on the NASDAQ Global Market, or NASDAQ, we have incurred and will continue to incur significant legal, accounting and otherexpenses. In addition, the Sarbanes-Oxley Act of 2002 and rules subsequently implemented by the Securities and Exchange Commission, or the SEC, andNASDAQ have imposed various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls andcorporate governance practices. Our management and other personnel will need to devote a substantial amount of time to these compliance initiatives. Moreover,these rules and regulations have increased our legal and financial compliance costs and are making some activities more time-consuming and costly. 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 control overfinancial reporting, and are required to include an attestation report on internal control over financial reporting issued by our independent registered publicaccounting firm. If we are unable to maintain effective internal controls, we may not have adequate, accurate or timely financial information, and we may be unableto meet our reporting obligations as a publicly traded company or comply with the requirements of the SEC or Section 404. This could result in a restatement of ourconsolidated financial statements, the imposition of sanctions, including the inability of registered broker dealers to make a market in our common shares, orinvestigation by regulatory authorities. Any such action or other negative results caused by our inability to meet our reporting requirements or comply with legaland regulatory requirements or by disclosure of an accounting, reporting or control issue could adversely affect the trading price of our securities60Table of Contentsand our business. Material weaknesses in our internal control over financial reporting could also reduce our ability to obtain financing or could increase the cost ofany financing we obtain.Our directors and executive officers, together with their affiliates, have substantial influence over us and could delay or prevent a change in corporate control. Our directors and executive officers, together with their affiliates, beneficially owned approximately 7.4 million shares of our common stock as ofDecember 31, 2015. These stockholders, acting together, have the ability to significantly influence the outcome of matters submitted to our stockholders forapproval, including the election of directors and any merger, consolidation or sale of all or substantially all of our assets. In addition, these stockholders, actingtogether, have the ability to significantly influence the management and affairs of our company. Accordingly, this concentration of ownership might harm themarket price of our common stock by:•delaying, deferring or preventing a change in corporate control; •impeding a merger, consolidation, takeover or other business combination involving us; or •discouraging a potential acquirer from making a tender offer or otherwise attempting to obtain control of us.Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result inadditional dilution of the percentage ownership of our stockholders and could cause our stock price to fall. Additional capital will be needed in the future to continue our planned operations. To the extent we raise additional capital by issuing equity securities, ourstockholders may experience substantial dilution. We may sell common stock, convertible securities or other equity securities in one or more transactions at pricesand in a manner we determine from time to time. If we sell common stock, convertible securities or other equity securities in more than one transaction, investorsmay be materially diluted by subsequent sales. These sales may also result in material dilution to our existing stockholders, and new investors could gain rightssuperior to our existing stockholders. Pursuant to our equity incentive plans, our management is authorized to grant stock options and other equity-based awards to our employees, directors andconsultants. We have reserved 6,159,510 shares of our common stock for issuance under our equity incentive plans as of December 31, 2015, which includes4,408,369 shares of common stock issuable upon the exercise of options outstanding as of December 31, 2015, and 25,000 shares of common stock issuable uponthe vesting of performance stock units, each of which will become eligible for sale in the public market in the future, subject to certain legal and contractuallimitations. In addition, as of December 31, 2015, warrants to purchase 631,588 shares of our common stock were outstanding. Shares of our common stock issuedupon exercise of these warrants may be sold in the public market, subject to prior registration or under an exemption from registration.If securities or industry analysts cease to publish research or publish inaccurate or unfavorable research about our business, our stock price and tradingvolume could decline. The trading market for our common stock depends in part on the research and reports that securities or industry analysts publish about us or our business. Ifone or more of the analysts who cover us downgrade our stock or publish inaccurate or unfavorable research about our business, our stock price would likelydecline. If one or more of these analysts cease coverage of our company or fail to publish reports on us regularly, demand for our stock could decrease, whichmight cause our stock price and trading volume to decline.61Table of ContentsWe may be required to pay severance benefits to our employees who are terminated in connection with a change in control, which could harm our financialcondition or results. Each of our executive officers is party to an employment agreement, and each of our other employees is party to an agreement or participates in a plan thatprovides change in control severance benefits including cash payments for severance and other benefits and acceleration of vesting of stock options and otherequity awards in the event of a termination of employment in connection with a change in control of us. The payment of these severance benefits could harm ourfinancial condition and results. The accelerated vesting of options and equity awards could result in dilution to our existing stockholders and harm the market priceof our common stock.Anti-takeover provisions contained in our restated certificate of incorporation and amended and restated bylaws, as well as provisions of Delaware law, couldimpair a takeover attempt. Our restated certificate of incorporation and our amended and restated bylaws contain provisions that could delay or prevent a change in control of ourcompany. These provisions could also make it more difficult for stockholders to elect directors and take other corporate actions. These provisions include:•a staggered board of directors; •authorizing the board to issue, without stockholder approval, preferred stock with rights senior to those of our common stock; •authorizing the board to amend our bylaws and to fill board vacancies until the next annual meeting of the stockholders; •prohibiting stockholder action by written consent; •limiting the liability of, and providing indemnification to, our directors and officers; •eliminating the ability of our stockholders to call special meetings; and •requiring advance notification of stockholder nominations and proposals. Section 203 of the Delaware General Corporation Law prohibits, subject to some exceptions, "business combinations" between a Delaware corporation and an"interested stockholder," which is generally defined as a stockholder who becomes a beneficial owner of 15% or more of a Delaware corporation's voting stock, fora three-year period following the date that the stockholder became an interested stockholder. These and other provisions in our restated certificate of incorporation and our amended and restated bylaws under Delaware law could discourage potentialtakeover attempts, reduce the price that investors might be willing to pay in the future for shares of our common stock and result in the market price of our commonstock being lower than it would be without these provisions.Our ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited. As of December 31, 2015, we had $419.5 million of federal and $323.0 million of state net operating loss carryforwards available to offset future taxableincome. Under Section 382 of the Internal Revenue Code of 1986, as amended, or the Code, if a corporation undergoes an "ownership change" (generally definedas a greater than 50% change (by value) in its equity ownership over a three year period), the corporation's ability to use its pre-change net operating losscarryforwards and other pre-change tax attributes to offset its post-change income may be limited. We are in the process of conducting a detailed analysis todetermine whether an ownership change under Section 382 of the Code has previously occurred. As a result, if we earn net taxable income, our ability to use ourpre-change net operating loss carryforwards to offset U.S. federal taxable income may become subject to limitations, which could potentially result in increasedfuture tax liability to us.62Table of ContentsITEM 1B. UNRESOLVED STAFF COMMENTS. None.ITEM 2. PROPERTIES. Details of each of our principal properties as of December 31, 2015 are provided below:ITEM 3. LEGAL PROCEEDINGS. We are not currently involved in any material legal proceedings.ITEM 4. MINE SAFETY DISCLOSURES. Not applicable.63Location Function Size (approximate square feet) Property InterestWaltham, MA, USA Corporate Headquarters 24,880 LeasedPasippany, NJ, USA Office space 10,530 LeasedCambridge, MA, USA Laboratory and office space 4,600 SubleasedTable of ContentsPART II ITEM 5. MARKET FOR REGISTRANT'S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITYSECURITIES Our common stock has been traded on The NASDAQ Global Market under the symbol "RDUS" since the initial public offering of our common stock onJune 6, 2014. Prior to that time there was no public market for our common stock. The following table presents reported quarterly high and low per share saleprices of our common stock on The NASDAQ Global Market for the periods presented. On February 19, 2016, the closing price of our common stock was $27.00 per share as reported on The NASDAQ Global Market.Stock Performance Graph This performance graph is furnished and shall not be deemed "filed" with the SEC or subject to Section 18 of the Exchange Act, nor shall it be deemedincorporated by reference in any filings under the Securities Act of 1933, as amended. The graph set forth below compares the cumulative total stockholder return on our common stock between June 6, 2014 (the date of the initial public offeringof our common stock) and December 31, 2015, with the cumulative total return of (a) the Nasdaq Biotechnology Index and (b) the Nasdaq Composite Index, overthe same period. This graph assumes the investment of $100 on June 6, 2014 in our common stock, the Nasdaq Biotechnology Index and the Nasdaq CompositeIndex and assumes the reinvestment of dividends, if any. The graph assumes our closing sales price on June 6, 2014 of $8.01 per share as the initial value of ourcommon stock and not the initial offering price to the public of $8.00 per share. The comparisons shown in the graph below are based upon historical data. We caution that the stock price performance shown in the graph below is notnecessarily indicative of, nor is it intended to forecast, the potential future performance of our common stock. Information used in the graph was obtained from theNasdaq Stock Market LLC, a financial data provider and a source believed to be reliable. The Nasdaq Stock Market LLC is not responsible for any errors oromissions in such information.642015 High Low Quarter Ended March 31, 2015 $51.22 $35.02 Quarter Ended June 30, 2015 69.16 34.76 Quarter Ended September 30, 2015 84.64 52.50 Quarter Ended December 31, 2015 77.10 45.89 2014 High Low Quarter Ended June 30, 2014 (beginning June 6, 2014) $14.60 $7.46 Quarter Ended September 30, 2014 24.28 8.09 Quarter Ended December 31, 2014 42.57 16.55 Table of Contents*$100 invested on June 6, 2014 in stock or indexHolders As of February 19, 2016, there were 69 holders of record of our common stock. The actual number of stockholders is greater than this number of recordholders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers and other nominees. This number of holders ofrecord also does not include stockholders whose shares may be held in trust by other entities.Dividends We have not paid any cash dividends on our common stock since inception and do not anticipate paying cash dividends in the foreseeable future.Recent Sales of Unregistered Securities We did not make any sales of unregistered securities during the fourth quarter ended December 31, 2015.Purchases of Equity Securities by the Issuer or Affiliated Purchasers There were no repurchases of shares of common stock made during the fourth quarter of the fiscal year ended December 31, 2015.65Table of ContentsITEM 6. SELECTED FINANCIAL DATA. You should read the following selected financial data together with our consolidated financial statements and the related notes contained in Item 8 of Part II ofthis Annual Report on Form 10-K. We have derived the statements of operations data for each of the three years ended December 31, 2013, 2014 and 2015 and thebalance sheets data as of December 31, 2014 and 2015 from the audited consolidated financial statements contained in Item 8 of Part II of this Form 10-K. Theselected balance sheet data as of December 31, 2011, 2012 and 2013 and the statement of operations data for the years ended December 31, 2011 and 2012 hasbeen derived from the audited financial statements for such years not included in this Form 10-K. The financial information set forth below for the year ended December 31, 2011 has been recast to reflect the adoption of Accounting Standards UpdateNo. 2011-05, Presentation of Comprehensive Income . The historical financial information set forth below may not be indicative of our future performance and should be read together with "Management'sDiscussion and Analysis of Financial Condition and Results of Operations" and our historical consolidated financial statements and notes to those statementsincluded in Item 7 of Part II and Item 8 of Part II, respectively, of this Annual Report on Form 10-K.66 Year Ended December 31, Statement of Operations and Comprehensive Loss Data 2015 2014 2013 2012 2011 (in thousands) Operating expenses: Research and development $68,280 $45,719 $60,536 $54,961 $36,179 General and administrative 30,797 13,674 6,829 9,469 5,330 Loss from operations (99,077) (59,393) (67,365) (64,430) (41,509)Other (expense) income: Other (expense) income, net (1,607) (713) 9,085 (2,095) (236)Interest (expense) income, net (842) (2,373) (2,410) (2,603) (731)Net loss (101,526) (62,479) (60,690) (69,128) (42,476)Other comprehensive loss, net of tax: Unrealized gain (loss) from available-for-salesecurities 26 (21) — (5) 8 Comprehensive loss $(101,500)$(62,500)$(60,690)$(69,133)$(42,468)Net (loss) earnings attributable to commonstockholders $(101,526)$(71,479)$(78,161)$(83,120)$113 Net (loss) earnings per share applicable to commonstockholders—basic $(2.56)$(4.04)$(203.91)$(225.71)$0.51 Net (loss) earnings per share applicable to commonstockholders—diluted $(2.56)$(4.04)$(203.91)$(225.71)$0.06 Weighted-average number of common shares used innet (loss) earnings per share applicable to commonstockholders—basic 39,643,099 17,699,487 383,310 368,261 219,254 Weighted-average number of common shares used innet (loss) earnings per share applicable to commonstockholders—diluted 39,643,099 17,699,487 383,310 368,261 1,774,935 Table of Contents67 As of December 31, Balance Sheet Data 2015 2014 2013 2012 2011 (in thousands) Cash and cash equivalents $159,678 $28,518 $12,303 $18,653 $25,128 Marketable securities 313,661 76,758 — 4,000 31,580 Working capital 459,128 86,774 (22,675) 8,026 56,607 Total assets 482,465 108,417 12,758 25,300 63,637 Long-term liabilities — 24,394 1,945 38,222 19,806 Total liabilities 21,180 44,953 37,257 55,312 26,589 Total convertible preferred stock and redeemable convertiblepreferred stock — — 252,802 170,649 156,658 Total liabilities, convertible preferred stock, redeemableconvertible preferred stock and stockholders' equity(deficit) 482,465 108,417 12,758 25,300 63,637 Table of ContentsITEM 7. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS. You should read the following discussions in conjunction with our consolidated financial statements and related notes included in this report. This discussionincludes forward-looking statements that involve risk and uncertainties. As a result of many factors, such as those set forth under "Risk Factors," actual resultsmay differ materially from those anticipated in these forward-looking statements.Executive Overview We are a science-driven biopharmaceutical company that is committed to developing innovative therapeutics in the areas of osteoporosis, oncology andendocrine diseases. Our lead product candidate, the investigational drug abaloparatide for subcutaneous injection, has completed Phase 3 development for potentialuse in the reduction of fracture risk in postmenopausal women with osteoporosis and is currently under regulatory review in Europe. Our clinical pipeline alsoincludes an investigational abaloparatide transdermal patch for potential use in osteoporosis and the investigational drug RAD1901 for potential use in hormone-driven, or hormone-resistant, breast cancer, and vasomotor symptoms in postmenopausal women. Our preclinical pipeline includes RAD140, a non-steroidalselective androgen receptor modulator, or SARM, under investigation for potential applications in oncology and multiple conditions where androgen modulationmay offer therapeutic benefit.Abaloparatide Abaloparatide is an investigational therapy for the potential treatment of women with postmenopausal osteoporosis who are at an increased risk for a fracture.Abaloparatide is a novel synthetic peptide analog that engages the parathyroid hormone receptor, or PTH1 receptor, and was selected for clinical developmentbased on its favorable bone building activity. Abaloparatide was created to have a unique mechanism of action with the goal of stimulating enhanced bone buildingactivity including bone formation, increasing bone mineral density, restoring bone microarchitecture and augmenting bone strength. We are developing twoformulations of abaloparatide:•Abaloparatide-SC —Abaloparatide has completed Phase 3 development for potential use as a daily self-administered injection, which we refer to asabaloparatide-SC. We hold worldwide commercialization rights to abaloparatide-SC, except for Japan. In December 2014, we announced thepositive 18-month top-line data from our Phase 3 ACTIVE clinical trial, in which abaloparatide-SC met the primary endpoint with a statisticallysignificant reduction in new vertebral fractures versus placebo, and in June 2015, we announced the positive top-line data from the first six monthsof the ACTIVExtend clinical trial and the 24-month combined data from ACTIVE and ACTIVExtend. In November 2015, we submitted amarketing authorization application, or MAA, to the European Medicines Agency, or EMA, which was validated and is currently undergoingregulatory review by the EMA. We intend to enter into one or more partnerships or collaborations for the potential commercialization ofabaloparatide-SC prior to a commercial launch. We plan to submit a new drug application, or NDA, in the United States, at the end of the firstquarter of 2016. Subject to regulatory review and a favorable regulatory outcome, we anticipate the first commercial sales of abaloparatide-SC willtake place in 2016. •Abaloparatide-TD —We are also developing abaloparatide-transdermal, which we refer to as abaloparatide-TD, based on 3M's patentedMicrostructured Transdermal System technology for potential use as a short wear-time transdermal patch. We hold worldwide commercializationrights to the abaloparatide-TD technology. During 2014, we reported progress towards the development of an optimized transdermal patch that maybe capable of demonstrating comparability to abaloparatide-SC. In preliminary, nonhuman primate pharmacokinetic studies, we achieved adesirable pharmacokinetic profile, with comparable AUC, Cmax, Tmax and T1/268Table of Contentsrelative to abaloparatide-SC. We believe that these results support continued clinical development of abaloparatide-TD toward future globalregulatory submissions as a potential post-approval line extension of the investigational drug abaloparatide-SC. We commenced a human replicativeclinical evaluation of the optimized abaloparatide-TD patch in December 2015, with the goal of achieving comparability to abaloparatide-SC. Weexpect to complete our clinical evaluation of the optimized abaloparatide-TD patch during 2016.RAD1901 RAD1901 is a selective estrogen receptor down-regulator/degrader, or SERD, that at high doses has a potential for use as an oral non-steroidal treatment forhormone-driven, or hormone-resistant, breast cancer. RAD1901 is currently being investigated in postmenopausal women with advanced estrogen receptorpositive, or ER-positive, HER2-negative breast cancer, the most common form of the disease. The compound has the potential for use as a single agent or incombination with other therapies to overcome endocrine resistance in breast cancer. In September 2015, we announced results from a Phase 1 maximum tolerated dose, or MTD, study of RAD1901 in 52 healthy volunteers. In the study,RAD1901 was administered to healthy postmenopausal women in doses ranging from 200mg to 1000mg, and the data showed that RAD1901 was well-toleratedand the overall safety was supportive of continued development. In addition, a subset of subjects that received 18F estradiol positron emission tomography, or FES-PET, imaging demonstrated suppression of the FES-PET signal to background levels after six days of dosing. In December 2014, we commenced a Phase 1, multicenter, open-label, two-part, dose-escalation study of RAD1901 in postmenopausal women with advancedER-positive and HER2-negative breast cancer in the United States to determine the recommended dose for a Phase 2 clinical trial and to make a preliminaryevaluation of the potential anti-tumor effect of RAD1901. We expect to complete this study by the middle of 2016. Dose escalation is currently ongoing with nodose limiting toxicities to date and we expect to initiate expansion cohorts in 2016. In December 2015, we commenced a Phase 1 FES-PET study in patients with metastatic breast cancer in the European Union which includes the use of FES-PET imaging to assess estrogen receptor occupancy in tumor lesions following RAD1901 treatment. In July 2015, we announced that early but promising preclinical data showed that our investigational drug RAD1901, in combination with Pfizer's palbociclib,a cyclin-dependent kinase, or CDK, 4/6 inhibitor, or Novartis' everolimus, an mTOR inhibitor, was effective in shrinking tumors. In patient-derived xenograft, orPDx, breast cancer models with either wild type or mutant ESR1, treatment with RAD1901 resulted in marked tumor growth inhibition, and the combination ofRAD1901 with either agent, palbociclib or everolimus, showed anti-tumor activity that was significantly greater than either agent alone. We believe that thispreclinical data suggest that RAD1901 has the potential to overcome endocrine resistance, is well-tolerated, and has a profile that is well suited for use incombination therapy. In January 2016 we entered into a worldwide clinical collaboration with Novartis Pharmaceuticals to evaluate the safety and efficacy of combining RAD1901,with Novartis' investigational agent LEE011 (ribociclib), a CDK 4/6 inhibitor, and BYL719 (alpelisib), an investigational phosphoinositide 3-kinase inhibitor. RAD1901 is also being evaluated at low doses as an estrogen receptor ligand for the potential relief of the frequency and severity of moderate to severe hotflashes in postmenopausal women with vasomotor symptoms. We commenced a Phase 2b clinical study of RAD1901 for the potential treatment of postmenopausalvasomotor symptoms in December 2015.69Table of ContentsFinancial OverviewResearch and Development Expenses Research and development expenses consist primarily of clinical testing costs, including payments made to contract research organizations, or CROs, salariesand related personnel costs, fees paid to consultants and outside service providers for regulatory and quality assurance support, licensing of drug compounds andother expenses relating to the manufacture, development, testing and enhancement of our investigational product candidates. We expense our research anddevelopment costs as they are incurred. None of the research and development expenses in relation to our investigational product candidates are currently borne by third parties. Our leadinvestigational product candidate is abaloparatide and it currently represents the largest portion of our research and development expenses for our investigationalproduct candidates. We began tracking program expenses for abaloparatide-SC in 2005, and program expenses from inception to December 31, 2015 wereapproximately $195.9 million. We began tracking program expenses for abaloparatide-TD in 2007, and program expenses from inception to December 31, 2015were approximately $33.7 million. We began tracking program expenses for RAD1901 in 2006, and program expenses from inception to December 31, 2015 wereapproximately $27.7 million. We began tracking program expenses for RAD140 in 2008, and program expenses from inception to December 31, 2015 wereapproximately $5.7 million. These expenses relate primarily to external costs associated with manufacturing, preclinical studies and clinical trial costs. Costs related to facilities, depreciation, stock-based compensation and research and development support services are not directly charged to programs as theybenefit multiple research programs that share resources. The following table sets forth our research and development expenses related to abaloparatide-SC, abaloparatide-TD, RAD1901 and RAD140 for the yearsended December 31, 2015, 2014 and 2013 (in thousands):General and Administrative Expenses General and administrative expenses consist primarily of salaries and related expenses for executive, finance and other administrative personnel, professionalfees, business insurance, rent, general legal activities, including the cost of maintaining our intellectual property portfolio, and other corporate expenses. Our results also include stock-based compensation expense as a result of the issuance of stock option grants and performance unit grants to employees,directors and consultants. The stock-based compensation expense is included in the respective categories of expense in the statement of operations (research anddevelopment and general and administrative expenses). We expect to record additional non-cash compensation expense in the future, which may be significant.Interest Income and Interest Expense Interest income reflects interest earned on our cash, cash equivalents and marketable securities.70 Year Ended December 31, 2015 2014 2013 Abaloparatide-SC $19,870 $32,044 $45,977 Abaloparatide-TD 2,585 1,493 11,459 RAD1901 9,926 2,250 — RAD140 495 — — Table of Contents Interest expense reflects interest due under our loan and security agreement, entered into on May 23, 2011 with General Electric Capital Corporation, orGECC, as agent and lender, and Oxford Finance, as a lender, or the Original Credit Facility, and our loan and security agreement entered into on May 30, 2014 withSolar Capital Ltd., or Solar, as agent and lender, and Oxford Finance, as lender, or the New Credit Facility. Under the Original Credit Facility, we drew$12.5 million under an initial and second term loan during the year ended December 31, 2011 and an additional $12.5 million under a third term loan during theyear ended December 31, 2012. Under the New Credit Facility, we drew $21.0 million under an initial term loan on May 30, 2014. On July 10, 2014, we enteredinto a first amendment to the New Credit Facility, or the First Amendment. Pursuant to the terms of the First Amendment, a second term loan of $4.0 million wasdrawn on July 10, 2014. On May 30, 2014, we used approximately $9.3 million of the New Credit Facility to repay all the amounts owed under the Original Credit Facility. On August 4, 2015, we prepaid all amounts owed under the Credit Facility and the First Amendment. After consideration of relevant fees required under theCredit Facility and the First Amendment, the total payment amounted to $26.5 million.Other Income (Expense) For the years ended December 31, 2014 and 2013, other income (expense) primarily reflects changes in the fair value of our warrant liability and the series A-6 convertible preferred stock liability and stock asset outstanding prior to our initial public offering from the date of the initial accrual to the reporting date.Critical Accounting Policies and Estimates The preparation of our consolidated financial statements requires us to make certain estimates and assumptions that affect the reported amounts of assets andliabilities and expenses during the reported periods. We believe the following accounting policies are "critical" because they require us to make judgments andestimates about matters that are uncertain at the time we make the estimate, and different estimates, which would have been reasonable, could have been used,which would have resulted in different financial results.Accrued Clinical Expenses When preparing our consolidated financial statements, we are required to estimate our accrued clinical expenses. This process involves reviewing opencontracts and purchase orders, communicating with our personnel to identify services that have been performed on our behalf and estimating the level of serviceperformed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual cost. Payments under some of thecontracts we have with parties depend on factors such as successful enrollment of certain numbers of patients, site initiation and the completion of clinical trialmilestones. Examples of estimated accrued clinical expenses include:•fees paid to investigative sites and laboratories in connection with clinical studies; •fees paid to CROs in connection with clinical studies, if CROs are used; and •fees paid to contract manufacturers in connection with the production of clinical study materials. When accruing clinical expenses, we estimate the time period over which services will be performed and the level of effort to be expended in each period. Ifpossible, we obtain information regarding unbilled services directly from our service providers. However, we may be required to estimate the cost of these servicesbased only on information available to us. If we underestimate or overestimate the cost associated with a trial or service at a given point in time, adjustments toresearch71Table of Contentsand development expenses may be necessary in future periods. Historically, our estimated accrued clinical expenses have approximated actual expense incurred.Subsequent changes in estimates may result in a material change in our accruals.Research and Development Expenses We account for research and development costs by expensing such costs to operations as incurred. Research and development costs primarily consist ofpersonnel costs, outsourced research activities, pre-commercial manufacturing activities, laboratory supplies and consulting fees. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred and capitalized.The capitalized amounts are expensed as the related goods are delivered or the services are performed. If expectations change such that we do not expect we willneed the goods to be delivered or the services to be rendered, capitalized nonrefundable advance payments would be charged to expense.Stock-based CompensationOptions We measure stock-based compensation cost at the accounting measurement date based on the fair value of the option, and recognize the expense on a straight-line basis over the requisite service period of the option, which is typically the vesting period. We estimate the fair value of each option using the Black-Scholes option pricing model that takes into account the fair value of our common stock, theexercise price, the expected life of the option, the expected volatility of our common stock, expected dividends on our common stock, and the risk-free interest rateover the expected life of the option. Due to the limited trading history of our common stock since our June 2014 initial public offering, we use the simplifiedmethod described in the SEC's Staff Accounting Bulletin No. 107, Share-Based Payment, to determine the expected life of the option grants. The estimate ofexpected volatility is based on a review of the historical volatility of similar publicly held companies in the biotechnology field over a period commensurate withthe option's expected term. We have never declared or paid any cash dividends on our common stock and we do not expect to do so in the foreseeable future.Accordingly, we use an expected dividend yield of zero. The risk-free rate is based on the U.S. Treasury yield curve in effect at the time of grant valuation for aperiod commensurate with the option's expected term. These assumptions are highly subjective and changes in them could significantly impact the value of theoption and hence the related compensation expense. We apply an estimated forfeiture rate to current period expense to recognize compensation expense only for those awards expected to vest. We estimateforfeitures based upon historical data, adjusted for known trends, and will adjust the estimate of forfeitures if actual forfeitures differ or are expected to differ fromsuch estimates. Subsequent changes in estimated forfeitures are recognized through a cumulative adjustment in the period of change and also will impact theamount of stock-based compensation expense in future periods. Stock-based compensation expense recognized for options granted to consultants is also based upon the fair value of the options issued, as determined by theBlack-Scholes option pricing model. However, the unvested portion of such option grants is re-measured at each reporting period, until such time as the option isfully vested.72Table of ContentsPerformance Units We measure stock-based compensation cost at the accounting measurement date based on the fair value of the performance unit grant, and recognize theexpense over the derived service period of the performance units. We estimate the fair value of each grant using a Monte Carlo simulation analysis that takes into account the forecasted price of our common stock, historicalvolatility of our common stock, risk-free rate as of valuation date, price of our common stock as of the grant date and the trigger for the performance condition tobe met. The derived service period for each grant is calculated using a Monte Carlo simulation analysis.Fair Value Measurements We define fair value as the price that would be received to sell an asset or be paid to transfer a liability in an orderly transaction between market participants atthe measurement date. We determine fair value based on the assumptions market participants use when pricing the asset or liability. We also use the fair valuehierarchy that prioritizes the information used to develop these assumptions. The fair value hierarchy gives the highest priority to unadjusted quoted prices in active markets for identical assets (Level 1) and the lowest priority tounobservable inputs (Level 3). Our financial assets and liabilities are classified within the fair value hierarchy based on the lowest level of input that is significantto the fair value measurement. The three levels of the fair value hierarchy, and its applicability to our financial assets, are described below:Level 1 —Unadjusted quoted prices in active markets that are accessible at the measurement date of identical, unrestricted assets.Level 2 —Quoted prices for similar assets, or inputs that are observable, either directly or indirectly, for substantially the full term throughcorroboration with observable market data. Level 2 includes investments valued at quoted prices adjusted for legal or contractual restrictionsspecific to the security.Level 3 —Pricing inputs are unobservable for the asset, that is, inputs that reflect the reporting entity's own assumptions about the assumptionsmarket participants would use in pricing the asset. Level 3 includes private investments that are supported by little or no market activity. As of December 31, 2015 and 2014, we held financial assets that were measured using Level 1 and Level 2 inputs. Assets measured using Level 1 inputsinclude money market funds, which are valued using quoted market prices with no valuation adjustments applied. Assets measured using Level 2 inputs includemarketable securities that consist primarily of domestic corporate debt securities (direct issuance bonds, corporate bonds, etc.) and are valued using third-partypricing resources, which generally use interest rates and yield curves observable at commonly quoted intervals of similar assets as observable inputs for pricing. As of December 31, 2015 and 2014, we held no Level 3 assets or liabilities.Results of Operations The following discussion summarizes the key factors our management team believes are necessary for an understanding of our consolidated financialstatements.73Table of ContentsYears Ended December 31, 2015 and December 31, 2014 Research and development expenses —For the year ended December 31, 2015, research and development expense was $68.3 million compared to$45.7 million for the year ended December 31, 2014, an increase of $22.6 million, or 49%. This increase was primarily a result of an increase in compensationexpense, including an increase of $5.9 million of non-cash stock-based compensation expense, due to an increase in headcount from 16 research and developmentemployees as of December 31, 2014 to 48 research and development employees as of December 31, 2015. This increase was also driven by higher consulting costsincurred to support our MAA and planned NDA submissions for our investigational product candidate abaloparatide-SC, and an increase in contract service costsassociated with the development of our investigational product candidate RAD1901 as a result of the initiation of various preclinical and manufacturing activities inlate 2014. These amounts were partially offset by a decrease in the total professional contract service costs associated with the development of abaloparatide-SCresulting from the completion of the Phase 3 18-month fracture study in October 2014 and the first six months of the ACTIVExtend clinical trial. We expect thatcosts associated with the development of abaloparatide-SC will continue to decrease over the course of the ACTIVExtend clinical trial as patients completetreatment. We expect that the costs associated with the development of abaloparatide-TD will increase as we begin to advance an optimized abaloparatide-TD product inadditional clinical studies. We expect that the costs associated with the development of RAD1901 will increase as we begin to advance RAD1901 through variouspreclinical and clinical studies, including a Phase 1 study in metastatic breast cancer, which commenced in late 2014, and a Phase 2b study in vasomotor symptoms,which commenced in December 2015. General and administrative expenses —For the year ended December 31, 2015, general and administrative expense was $30.8 million compared to$13.7 million for the year ended December 31, 2014, an increase of $17.1 million, or 125%. This increase was primarily the result of an increase during the yearended December 31, 2015, of approximately $10.3 million in legal fees and professional support costs, including the costs associated with growing Radius'headcount and preparing for the potential commercialization of abaloparatide-SC, subject to a favorable regulatory review. This increase was also driven by anincrease in compensation expense, including an increase of $1.8 million of non-cash stock-based compensation expense, due to an increase in headcount from 10general and administrative employees as of December 31, 2014 to 27 general and administrative employees as of December 31, 2015.74 Years Ended December 31, Change 2015 2014 $ % (in thousands) Operating expenses: Research and development $68,280 $45,719 $22,561 49%General and administrative 30,797 13,674 17,123 125%Loss from operations (99,077) (59,393) 39,684 67%Other (expense) income: Other (expense) income, net (35) (510) (475) –93%Loss on retirement of note payable (1,572) (203) 1,369 674%Interest (expense) income, net (842) (2,373) (1,531) –65%Net loss $(101,526)$(62,479) 39,047 62%Table of Contents Other (expense) income, net —For the year ended December 31, 2015, other expense, net of other income, was $35 thousand, as compared to $0.5 millionduring the year ended December 31, 2014. Other expense, net of other income, for the year ended December 31, 2015 consisted primarily of state taxes. The$0.5 million of other expense, net of income, for the year ended December 31, 2014 was primarily due to an increase in the fair value of our warrant liability as aresult of an overall increase in the fair value of the underlying common stock from December 31, 2013 to June 6, 2014. Following our initial public offering onJune 6, 2014, the carrying value of our warrant liability was reclassified to equity. Loss on retirement of note payable —For the year ended December 31, 2015, loss on retirement of note payable was $1.6 million. This loss was a result of theprepayment of our New Credit Facility on August 4, 2015. For the year ended December 31, 2014, loss on retirement of note payable was $0.2 million. This losswas a result of the prepayment of our Original Credit Facility on May 30, 2014. Interest (expense) income —For the year ended December 31, 2015, interest expense, net of interest income, was $0.8 million, as compared to $2.4 millionduring the year ended December 31, 2014, a decrease of $1.5 million, or 65%. This decrease was primarily a result of the prepayment of all outstanding long-termdebt on August 4, 2015, and an increase in interest income as a result of an increase in our cash, cash equivalents and marketable securities outstanding during theyear ended December 31, 2015.Years Ended December 31, 2014 and December 31, 2013 Research and development expenses —For the year ended December 31, 2014, research and development expense was $45.7 million compared to$60.5 million for the year ended December 31, 2013, a decrease of $14.8 million, or 24%. This decrease is primarily a result of a decrease in the total professionalcontract service costs associated with the development of abaloparatide-SC and abaloparatide-TD, partially offset by an increase in professional contract servicescosts associated with the development of RAD1901. During the year ended December 31, 2014, we incurred professional contract service costs associated with thedevelopment of abaloparatide-SC, abaloparatide-TD and RAD1901 of $32.0 million, $1.5 million and $2.3 million, respectively, compared to $46.0 million,$11.5 million and zero, respectively, for the year ended December 31, 2013. The decrease in contract service costs associated with the development ofabaloparatide-SC is primarily a result of the completion of the Phase 3 18-month fracture study in October 2014. Additionally, fewer patients were enrolled in the6-month extension study as of December 31, 2014, as compared to the year ended December 31, 2013, as certain patients completed treatment. In addition, therewill be variability from quarter to quarter in the costs for abaloparatide-SC, driven primarily by the euro/dollar exchange rate,75 Years Ended December 31, Change 2014 2013 $ % (in thousands) Operating expenses: Research and development $45,719 $60,536 $(14,817) –24%General and administrative 13,674 6,829 6,845 100%Loss from operations (59,393) (67,365) (7,972) –12%Other (expense) income: Other (expense) income, net (510) 9,085 9,595 106%Loss on retirement of note payable (203) — 203 100%Interest (expense) income, net (2,373) (2,410) (37) –2%Net loss $(62,479)$(60,690) 1,789 3%Table of Contentswhich is more fully described below under "Research and Development Agreements." The decrease in contract service costs associated with the development ofabaloparatide-TD is a result of the completion of the Phase 2 clinical trial (which began dosing patients in September 2012) in September 2013. The increase incontract service costs associated with the development of RAD1901 is a result of the initiation of various preclinical, clinical, and manufacturing activities in 2014. General and administrative expenses —For the year ended December 31, 2014, general and administrative expense was $13.7 million compared to$6.8 million for the year ended December 31, 2013, an increase of $6.8 million, or 100%. This increase was primarily due to an increase in compensation costs of$4.5 million, including an increase of $3.9 million in non-cash stock-based compensation expense as a result of the issuance of new option awards during 2014, aswell as the acceleration of vesting for a portion of our Chief Executive Officer's outstanding option awards, in accordance with his employment agreement, uponcompletion of our initial public offering. This increase can also be attributed to higher legal fees and consulting support costs of approximately $1.7 million duringthe year ended December 31, 2014. Other (expense) income, net —For the year ended December 31, 2014, other expense, net of other income, was $0.5 million, as compared to other income, netof expense during the year ended December 31, 2013 of $9.1 million. Other expense, net of other income, primarily reflects changes in the fair value of the stockasset, stock liability, other liability and warrant liability. The $0.5 million of other expense, net of income, for the year ended December 31, 2014 was primarily dueto an increase in the fair value of our warrant liability as a result of an overall increase in the fair value of the underlying common stock from December 31, 2013 toJune 6, 2014. Following our initial public offering on June 6, 2014, our warrant liability was reclassified to equity. The $9.1 million of other income, net ofexpense, as of December 31, 2013 was primarily due to a decrease in the fair value of our stock liability and other liability as a result of an overall decline in thefair value of the underlying convertible preferred stock from December 31, 2012 to December 31, 2013. Loss on retirement of note payable —For the year ended December 31, 2014, loss on retirement of note payable was $0.2 million. This loss was a result of theprepayment of our Original Credit Facility on May 30, 2014. Interest (expense) income —For the year ended December 31, 2014, interest expense, net of interest income, was $2.4 million, consistent with $2.4 million forthe year ended December 31, 2013.Liquidity and Capital Resources From inception to December 31, 2015, we have incurred an accumulated deficit of $445.8 million, primarily as a result of expenses incurred through acombination of research and development activities related to our various investigational product candidates and expenses supporting those activities. Our totalcash, cash equivalents and marketable securities balance as of December 31, 2015 was $473.3 million. We have financed our operations since inception primarilythrough the public offerings of our common stock, private sale of preferred stock, borrowing under credit facilities and the receipt of $5.0 million in fees associatedwith an option agreement. Based upon our cash, cash equivalents and marketable securities balance, we believe that, prior to the consideration of revenue from the potential future salesof any of our investigational products that may receive regulatory approval or proceeds from partnership activities, we have sufficient capital to fund ourdevelopment plans, U.S. commercial scale-up and other operational activities into 2018. We expect to finance the future development costs of our clinical productportfolio with our existing cash, cash equivalents and marketable securities, or through strategic financing opportunities, that could include, but are not limited topartnering or other collaboration agreements, future offerings of equity, or the incurrence of debt. However, there is no guarantee that any of these strategicfinancing76Table of Contentsopportunities will be available to us on favorable terms, and some could be dilutive to existing stockholders. Our future capital requirements will depend on manyfactors, including the scope and progress made in our research and development and commercialization activities, the results of our clinical trials, and the reviewand potential approval of our products by the U.S. Food and Drug Administration, or FDA, and the European Medicines Agency. The successful development ofour investigational product candidates is subject to numerous risks and uncertainties associated with developing drugs, which could have a significant impact on thecost and timing associated with the development of our product candidates. If we fail to obtain additional future capital, we may be unable to complete our plannedpreclinical and clinical trials and obtain approval of any investigational product candidates from the FDA and foreign regulatory authorities. The following table sets forth the major sources and uses of cash for each of the periods set forth below (in thousands):Cash Flows from Operating Activities Net cash used in operating activities during the year ended December 31, 2015 was $87.1 million, which was primarily the result of a net loss of$101.5 million and net changes in working capital of $4.0 million, partially offset by $18.4 million of net non-cash adjustments to reconcile net loss to net cashused in operations. The $101.5 million net loss was primarily due to abaloparatide-SC and pipeline program development expenses along with employeecompensation and consulting costs incurred to support future regulatory submissions and preparation for the potential commercial launch of abaloparatide-SC. The$18.4 million net non-cash adjustments to reconcile net loss to net cash used in operations included stock-based compensation expense of $14.7 million, loss onretirement of note payable of $1.6 million and amortization of premiums (discounts) on marketable securities of $1.7 million. Net cash used in operating activities during the year ended December 31, 2014 was $48.3 million, which was primarily the result of a net loss of $62.5 million,partially offset by $11.2 million of net non-cash adjustments to reconcile net loss to net cash used in operations and net changes in working capital of $3.0 million.The $62.5 million net loss was primarily due to expenses incurred in connection with our ongoing Phase 3 clinical trial of abaloparatide-SC. The $11.2 million netnon-cash adjustments to reconcile net loss to net cash used in operations included stock-based compensation expense of $7.1 million, $2.7 million of research anddevelopment expenses settled in stock, and a $0.5 million increase in the fair value of our warrant liability and stock liability as a result of an increase in the fairvalue of the underlying convertible preferred stock and common stock from December 31, 2013 to June 6, 2014. Net cash used in operating activities for the year ended December 31, 2013 was $45.0 million, which was primarily the result of a net loss of $60.7 million,partially offset by net changes in working capital of $9.7 million and $6.0 million net non-cash adjustments to reconcile net loss to net cash used in operations. The$60.7 million net loss was primarily due to expenses incurred in connection with our Phase 3 clinical trial of abaloparatide-SC and our Phase 2 clinical study ofabaloparatide-TD, which77 Years ended December 31, 2015 2014 2013 Net cash (used in) provided by: Operating activities $(87,103)$(48,345)$(45,017)Investing activities (239,822) (78,065) 3,971 Financing activities 458,085 142,625 34,696 Net increase (decrease) in cash and cash equivalents $131,160 $16,215 $(6,350)Table of Contentsfinished dosing patients during the three months ended September 30, 2013. The $6.0 million net non-cash adjustments to reconcile net loss to net cash used inoperations included $13.1 million of research and development expenses settled in stock and stock-based compensation expense of $1.5 million, and was partiallyoffset by a $9.1 million reduction in the fair value of our warrant liability, stock liability and other liability as a result of a decline in the fair value of the underlyingconvertible preferred stock from December 31, 2012 to December 31, 2013.Cash Flows from Investing Activities Net cash used in investing activities for the year ended December 31, 2015 was $239.8 million, as compared to net cash used in investing activities of$78.1 million for the year ended December 31, 2014. The net cash used in investing activities during the year ended December 31, 2015 was primarily a result of $579.1 million in purchases of marketablesecurities and $1.2 million of purchases of property and equipment, partially offset by $340.5 million of net proceeds received from the sale or maturity ofmarketable securities. The net cash used in investing activities during the year ended December 31, 2014 was primarily a result of $97.7 million in purchases ofmarketable securities and $0.9 million of purchases of property and equipment, partially offset by $20.5 million of net proceeds received from the sale or maturityof marketable securities. The net cash provided by investing activities during the year ended December 31, 2013 was primarily a result of $21.0 million netproceeds received from the sale or maturity of marketable securities, partially offset by $17.1 million in purchases of marketable securities. Our investing cash flows will be impacted by the timing of purchases and sales of marketable securities. All of our marketable securities have contractualmaturities of less than one year. Due to the short-term nature of our marketable securities, we would not expect our operational results or cash flows to besignificantly affected by a change in market interest rates due to the short-term duration of our investments.Cash Flows from Financing Activities Net cash provided by financing activities for the year ended December 31, 2015 was $458.1 million, as compared to $142.6 million of net cash provided byfinancing activities for the year ended December 31, 2014. Net cash provided by financing activities during the year ended December 31, 2015 consisted of $482.3 million of net proceeds received from public offeringsof our common stock in January and July of 2015, partially offset by the repayment of our New Credit Facility. Net cash provided by financing activities during the year ended December 31, 2014 consisted of $50.4 million of net proceeds from our initial public offering,$53.4 million of net proceeds from our additional public offering that closed October 7, 2014, $27.4 million of net proceeds from the issuance of our series B-2convertible preferred stock in February and March of 2014, and $24.6 million of net proceeds from our New Credit Facility, partially offset by payments under ourOriginal Credit Facility of $13.2 million. Net cash provided by financing activities for the year ended December 31, 2013 consisted of $42.9 million of net proceeds from the issuance of our series Bconvertible preferred stock in April and May of 2013, partially offset by payments under our Credit Facility of $8.2 million.Sales of Common Stock On July 28, 2015, we completed a public offering of 4,054,054 shares of our common stock at a price of $74.00 per share, for aggregate proceeds, net ofunderwriting discounts, commissions and78Table of Contentsoffering costs, of approximately $281.5 million. Also, on July 28, 2015, the underwriters purchased an additional 608,108 shares by exercising an option topurchase additional shares that was granted to them in connection with the offering. As a result of the public offering and subsequent exercise of the underwriters'option, we received aggregate proceeds, net of underwriting discounts, commissions and estimated offering costs of approximately $323.8 million. On January 28, 2015, we completed a public offering of 4,000,000 shares of our common stock at a price of $36.75 per share, for aggregate estimatedproceeds, net of underwriting discounts, commissions and offering costs, of approximately $137.8 million. On January 28, 2015, the underwriters purchased anadditional 600,000 shares in the aggregate by exercising an option to purchase additional shares that was granted to them in connection with the offering. As aresult of the public offering and subsequent exercise of the underwriters' option, we received aggregate proceeds, net of underwriting discounts, commissions andoffering costs of approximately $158.4 million. On October 7, 2014, we completed an additional public offering whereby we sold 2,750,000 shares of common stock at a price of $18.25 per share, foraggregate proceeds, net of underwriting discounts, commissions and offering costs, of approximately $46.9 million. On October 7, 2014, the underwriterspurchased an additional 378,524 shares in the aggregate by exercising a portion of the over-allotment option granted to them in connection with the offering. As aresult of the public offering and subsequent exercise of the over-allotment option, we received aggregate proceeds, net of underwriting discounts, commissions andoffering costs of approximately $53.4 million. On June 11, 2014, we completed our initial public offering whereby we sold 6,500,000 shares of our common stock at a price of $8.00 per share. The sharesbegan trading on the NASDAQ Global Market on June 6, 2014. In connection with the completion of the offering, all outstanding shares of our convertiblepreferred stock converted into 19,465,132 shares of common stock, and 2,862,654 shares of common stock were issued in satisfaction of accumulated dividendsaccrued on the preferred stock. In addition, all outstanding warrants to purchase shares of series A-1 convertible preferred stock and warrants to purchase shares ofseries B-2 convertible preferred stock were converted into the right to purchase 149,452 shares of common stock and our warrant liability was reclassified toequity. On June 18, 2014 and June 25, 2014, the underwriters purchased an additional 512,744 shares in the aggregate by exercising a portion of the over-allotmentoption granted to them in connection with the initial public offering. As a result of the closing of the initial public offering and subsequent exercise of the over-allotment option, we received aggregate proceeds, net of underwriting discounts, commissions and offering costs, of approximately $50.4 million.79Table of ContentsSales of Preferred Stock We had no sales of preferred stock during the year ended December 31, 2015. Through December 31, 2015, we had received aggregate net cash proceeds of$238.2 million from the sale of shares of our preferred stock as follows: On February 14, 2014, we entered into a Series B-2 Convertible Preferred Stock and Warrant Purchase Agreement, or Purchase Agreement, pursuant to whichwe were able to raise up to approximately $40.2 million through the issuance of (1) up to 655,000 series B-2 Shares convertible preferred stock, or Series B-2, parvalue $.0001 per share, and (2) warrants to acquire up to 718,201 shares of our common stock, at an exercise price of $14.004 per share. On February 14, 2014,February 19, 2014, February 24, 2014, March 14, 2014 and March 28, 2014, we consummated closings under the Series B-2 Purchase Agreement, whereby, inexchange for aggregate proceeds to us of approximately $27.5 million, we issued an aggregate of 448,060 Series B-2 Shares and warrants to purchase up to a totalof 491,293 shares of our common stock. The warrants issuable pursuant to the Purchase Agreement are exercisable for a period of five years from issuance. On April 23, 2013, we entered into a Series B Convertible Preferred Stock and Warrant Purchase Agreement, or the Series B Purchase Agreement, pursuant towhich we could raise, at any time on or prior to May 10, 2013, up to approximately $60.0 million through the issuance of (1) up to 980,000 shares of its Series Bpreferred stock , or the Series B, and (2) warrants to acquire up to approximately 1,075,000 shares of its common stock with an exercise price of $14.004 per share.On April 23, 2013, we consummated a first closing under the Series B Purchase Agreement, whereby in exchange for aggregate proceeds of approximately$43.0 million, we issued 700,098 shares of Series B and warrants to purchase up to a total of 767,651 shares of our common stock. On May 10, 2013, weconsummated a second closing under the Series B Purchase Agreement, whereby in exchange for aggregate proceeds of approximately $0.1 million, we issued1,137 shares of Series B and warrants to purchase up to a total of 1,246 shares of our common stock. The warrants can be exercised at any time prior to the fifthanniversary of their issuance. Upon completion of our initial public offering, all shares of preferred stock were converted into shares of our common stock.80Issue Year No. Shares Net Proceeds (in thousands) Series B redeemable convertible preferred stock(1) 2003, 2004, 2005 1,599,997 $23,775 Series C redeemable convertible preferred stock(1) 2006, 2007, 2008 10,146,629 82,096 Series A-1 convertible preferred stock(1) 2011 9,223,041 61,591 Series A-5 convertible preferred stock(1) 2011 64,430 525 Series B convertible preferred stock 2013 701,235 42,870 Series B-2 convertible preferred stock 2014 448,060 27,368 Total 22,183,392 $238,225 (1)Share amounts stated in pre-Merger shares, which converted into the rights to one-tenth of one share pursuant to the Merger.Table of ContentsDebt Borrowings On May 30, 2014, we entered into our New Credit Facility with Solar and Oxford Finance, pursuant to which Solar and Oxford agreed to make available to us$30.0 million in the aggregate subject to certain conditions to funding. An initial term loan was made on May 30, 2014 in an aggregate principal amount equal to$21.0 million, or the Initial Term Loan. The Initial Term Loan bore interest per annum at 9.85% plus one-month LIBOR (customarily defined). All principal and accrued interest on the initial termloan had been due on June 1, 2018. As security for its obligations under the New Credit Facility, we granted a security interest in substantially all of our existing and after-acquired assets exceptfor our intellectual property and certain other customary exclusions. On July 10, 2014, we entered into a first amendment to the New Credit Facility, or the First Amendment. Pursuant to the terms of the First Amendment, asecond term loan of $4.0 million was drawn on July 10, 2014. On August 4, 2015, the Company prepaid all amounts owed under the Credit Facility and the First Amendment. After consideration of relevant fees requiredunder the Credit Facility and the First Amendment, the total payment amounted to $26.5 million.Future Financing Needs We expect to finance the future development costs of our clinical product portfolio with our existing cash and cash equivalents and marketable securities, orthrough strategic financing opportunities, that could include, but are not limited to partnering or other collaboration agreements, future offerings of our equity, orthe incurrence of debt. We anticipate that we will make determinations as to which additional programs to pursue and how much funding to direct to each programon an ongoing basis in response to the scientific and clinical data of each investigational product candidate, progress on securing third-party collaborators, as wellas ongoing assessments of such investigational product candidate's commercial potential and our ability to fund this product development. The successful development of our investigational product candidates is subject to numerous risks and uncertainties associated with developing drugs,including, but not limited to, the variables listed below. A change in the outcome of any of these variables with respect to the development of any of ourinvestigational product candidates could mean a significant change in the cost and timing associated with the development of that investigational product candidate. Abaloparatide-SC is our only investigational product candidate in late stage development, and our business currently depends heavily on its successfuldevelopment, regulatory approval and commercialization. We submitted an MAA to the EMA in November 2015 and plan to submit an NDA to the FDA at the endof the first quarter of 2016. Obtaining approval of an investigational product candidate is an extensive, lengthy, expensive and uncertain process, and any approvalof abaloparatide-SC may be delayed, limited or denied for many reasons, including:•we may not be able to demonstrate that abaloparatide is safe and effective as a treatment for reduction of fracture risk in postmenopausal womenwith osteoporosis to the satisfaction of the FDA or other foreign regulatory authorities; •the results of our clinical studies may not meet the level of statistical or clinical significance required for marketing approval; •the FDA or other foreign regulatory authorities may disagree with the number, design, size, conduct or implementation of our clinical studies;81Table of Contents•the CRO that we retain to conduct clinical studies may take actions outside of our control that materially adversely impact our clinical studies; •the FDA or other foreign regulatory authorities may not find the data from preclinical studies and clinical studies sufficient to demonstrate thatabaloparatide's clinical and other potential benefits outweigh its safety risks; •the FDA or other foreign regulatory authorities may disagree with our interpretation of data from our preclinical studies and clinical studies or mayrequire that we conduct additional studies; •the FDA or other foreign regulatory authorities may not agree with our proposed labeling and may require labeling that undermines or otherwisesignificantly impairs the commercial value of the product if it were to be approved with such labeling; •the FDA or other foreign regulatory authorities may not accept data generated at our clinical study sites; •the FDA may require development of a Risk Evaluation and Mitigation Strategy, or REMS, as a condition of approval; •if our NDA is reviewed by an advisory committee, the FDA may have difficulties scheduling an advisory committee meeting in a timely manner orthe advisory committee may recommend against approval of our application or may recommend that the FDA require, as a condition of approval,additional preclinical studies or clinical studies, limitations on approved labeling or distribution and use restrictions; or •the FDA or other foreign regulatory authorities may identify deficiencies in the manufacturing processes or facilities of our third-partymanufacturers. In addition, the FDA or other foreign regulatory authorities may change their approval policies or adopt new regulations.Contractual Obligations and Commitments Contractual obligations represent future cash commitments and liabilities under agreements with third parties, and exclude contingent liabilities for which wecannot reasonably predict future payment. We enter into contracts in the normal course of business with CROs for preclinical and clinical research studies, researchsupplies and other services and products for operating purposes. These contracts generally provide for termination on notice, and therefore are cancelable contractsand not included in the table of contractual obligations and commitments. In addition, we have certain obligations to make future payments to third parties thatbecome due and payable on the achievement of certain development, regulatory and commercial milestones (such as the start of a clinical trial, filing of an NDA,approval by the FDA or product launch). The table below excludes these potential payments we may be required to make under our agreements because the timingof payments and actual amounts paid under those agreements may be different depending on the timing of receipt of goods or services or changes to agreed-uponterms or amounts for some obligations, and those agreements are cancelable upon written notice by us and therefore, not long-term liabilities. Additionally, theexpected timing of payment of the obligations presented below is estimated based on current information. Our contractual obligations result from property leases for office space. However, more information regarding significant contracts with CROs and ourobligations to make future payments to third parties that become due and payable upon achievement of certain development, regulatory and commercial milestonescan be found below under "Research and Development Agreements" and "License Agreement Obligations".82Table of Contents The following table summarizes our contractual obligations at December 31, 2015:Research and Development Agreements Abaloparatide-SC Phase 3 Clinical Trial —We have entered into agreements with Nordic Bioscience Clinical Development VII A/S, or Nordic, to conductour Phase 3 clinical trial of abaloparatide-SC, or the Phase 3 Clinical Trial. On March 29, 2011, we entered into a Clinical Trial Services Agreement, or the ClinicalTrial Services Agreement. On the same date, we also entered into Work Statement NB-1, as amended on December 9, 2011, June 18, 2012, March 28, 2014,May 19, 2014, July 22, 2014, August 15, 2014 and March 12, 2015, or Work Statement NB-1, and the Stock Issuance Agreement, as amended and restated onMay 16, 2011, and as further amended on February 21, 2013, March 28, 2014, and May 19, 2014, or the Stock Issuance Agreement. We recognized research and development expense for the amounts due to Nordic under the Work Statement NB-1 ratably over the estimated per patienttreatment period beginning upon enrollment in the Phase 3 Clinical Trial, or a twenty-month period, except for the amounts due under the fourth amendment to theWork Statement NB-1, which we recognized on a per patient basis when the end-of-study visit and all other required procedures were completed. We recorded noexpense, $8.2 million, and $31.6 million of research and development expense during the years ended December 31, 2015, 2014, and 2013, respectively for perpatient costs incurred for patients that had enrolled in the Phase 3 Clinical Study. As of December 31, 2015, all obligations due to Nordic under Work StatementNB-1 had been paid. Abaloparatide-SC Phase 3 Clinical Extension Study —On February 21, 2013, we entered into the Work Statement NB-3, as amended on February 28, 2014,March 23, 2015, July 8, 2015 and October 21, 2015, or the Work Statement NB-3. Pursuant to the Work Statement NB-3, Nordic performed an extension study toevaluate six months of standard-of-care osteoporosis management following the completion of the Phase 3 clinical trial of abaloparatide-SC, or the ExtensionStudy, and, upon completion of this initial six months, an additional period of 18 months of standard-of-care osteoporosis management, or the Second Extension. In April 2015, we entered into an amendment to the Work Statement NB-3, or the NB-3 Amendment. The NB-3 Amendment was effective as of March 23,2015 and provides that Nordic will perform additional services, including monitoring of patients enrolled in the Second Extension. Payments in cash to be made toNordic under the NB-3 Amendment are denominated in euros and total up to approximately €4.1 million ($4.5 million). Payments in cash to be made to Nordic under the Work Statement NB-3 are denominated in both euros and U.S. dollars and total up to €11.9 million($12.9 million) and $1.1 million, respectively. In addition, payments are due to Nordic in connection with the Work Statement NB-3 pursuant to the Stock IssuanceAgreement, as discussed below. As of December 31, 2015, services related to the Second Extension are ongoing and all obligations due to Nordic in relation to theExtension Study have been paid. We recognize research and development expense for the amounts due to Nordic under the Extension Study and the Second Extension ratably over theestimated per patient treatment periods beginning upon enrollment or over a nine-month and nineteen-month period, respectively. We recorded $5.4 million,$9.6 million, and $4.5 million of research and development expense during the years ended December 31, 2015, 2014, and 2013, respectively, respectively, for perpatient costs incurred.83 Total Less than 1 Year 1 to 3 Years 3 to 5 Years More than 5 Years (in thousands) Operating lease obligations $8,273 $1,944 $3,827 $2,502 $— Table of Contents As of December 31, 2015, we had a liability of $2.9 million reflected in accrued expenses and other current liabilities on the balance sheet resulting fromservices provided by Nordic under the Second Extension, which are payable in cash. Stock Issuance Agreement —Pursuant to the Stock Issuance Agreement, Nordic agreed to purchase 6,443 shares of our Series A-5 convertible preferred stock,which provided them with the right to receive quarterly stock dividends, payable in shares of our Series A-6 convertible preferred stock, for services rendered underWork Statement NB-1 and Work Statement NB-3. The Stock Issuance Agreement was later amended to provide that in the event an initial public offering of ourcommon stock occurred prior to June 30, 2014, any rights to receive stock dividends in relation to Work Statement NB-1 and Work Statement NB-3, for all periodsof time after 2014, would be changed from the right to receive stock to the right to receive a total cash payment of $4.3 million, payable in ten equal monthlyinstallments of $430,000 beginning on March 31, 2015. The amendment also stipulated that all consideration to be paid to Nordic pursuant to the Stock IssuanceAgreement at any time after the consummation of an initial public offering be payable in cash. As we completed an initial public offering on June 11, 2014, Nordicno longer has the right to receive stock and has been paid in cash for all periods after June 11, 2014. We are also responsible for certain pass-through costs in connection with the clinical trials noted above. Pass-through costs are expensed as incurred or upondelivery. We recognized research and development expense of $1.1 million, $1.3 million, and $3.9 million for pass through costs during years ended December 31,2015, 2014, and 2013, respectively. We estimate that our future cash obligations to Nordic in relation to Work Statement NB-3 will approximate the following as of December 31, 2015 (inthousands):License Agreement ObligationsAbaloparatide In September 2005, we exclusively licensed the worldwide rights (except for development and commercial rights in Japan) to abaloparatide and analogs froman affiliate of Ipsen Pharma SAS, or Ipsen, including US Patent No. 5,969,095 (statutory term expires March 29, 2016) entitled "Analogs of Parathyroid Hormone"that claims abaloparatide and US Patent No. 6,544,949, (statutory term expires March 29, 2016) entitled "Analogs of Parathyroid Hormone" that claimsabaloparatide and US Patent No. 6,544,949, (effective filing date March 29, 1996, statutory term expires March 29, 2016), entitled "Analogs of ParathyroidHormone" that claims methods of treating osteoporosis using abaloparatide and pharmaceutical compositions comprising abaloparatide, and the correspondingforeign patents and continuing patent applications. European Patent No. 0847278, which was included in the license from Ipsen and claimed the composition ofmatter of abaloparatide, lapsed due to Ipsen's failure to pay annuities. We are pursuing restoration of those rights. To date, the patent rights in Austria, Belgium,Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Sweden, and United Kingdom have been restored. We believe that the dataand market exclusivity provided in Europe for a new chemical entity, coupled with the need for a potential competitor to conduct clinical84 TOTAL(1) LESS THAN 1 YEAR(1) 1 - 3 YEARS(1) EURO DENOMINATED PAYMENTS EURO DENOMINATED PAYMENTS EURO DENOMINATED PAYMENTS EURO USD EQUIVALENT(2) USD DENOMINATEDPAYMENTS EURO USD EQUIVALENT(2) USD DENOMINATEDPAYMENTS EURO USD EQUIVALENT(2) USD DENOMINATEDPAYMENTS WorkStatementNB-3 €4,748 $5,156 $430 €4,349 $4,723 $430 €399 $433 $— TotalPayments €4,748 $5,156 $430 €4,349 $4,723 $430 €399 $433 $— (1)The amounts above exclude pass-through costs and, in accordance with work statement NB-3, may be adjusted from time to time and at the end of the study to reflect actual studyactivities completed by the study subjects. (2)USD equivalent is based upon the noon buying rate published by the Board of Governors of the Federal Reserve on December 31, 2015.Table of Contentstrials will likely provide a longer barrier to entry than the patent protection provided by the original European patent term, which will expire in 2016. We also have rights to joint intellectual property related to abaloparatide, including rights to the jointly derived intellectual property contained in US PatentNo. 7,803,770 (statutory term expires October 3, 2027, and may be extended to March 26, 2028 with 175 days of patent term adjustment due to delays in patentprosecution by the United States Patent and Trademark Office, or USPTO), US Patent No. 8,148,333 (statutory term expires October 3, 2027 and may be extendedto November 8, 2027 with 36 days of patent term adjustment due to delays in patent prosecution by the USPTO) and related patents and patent applications both inthe United States and worldwide that cover the method of treating osteoporosis using the Phase 3 Clinical Trial dosage strength and form. A correspondingEuropean application is pending with claims to the intended therapeutic formulation for abaloparatide-SC. Examination has been requested, but substantiveexamination has not yet commenced. Upon grant, this patent could be validated in any designated contracting or extension states and potentially could beconsidered for a Supplemental Protection Certificate depending upon the timing of its grant. Related cases granted in China, Australia, Singapore, Japan, Israel,Mexico, New Zealand, Russia and Ukraine, and currently pending in Europe, Canada, Brazil, Singapore, South Korea, India, Norway, and Hong Kong will have apatent expiration date of 2027. Patent applications which cover various aspects of abaloparatide for microneedle application are pending in the United States,Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, Korea, Mexico, New Zealand, Russia, Singapore, and Ukraine. Any patents that mightissue from these applications will have an expiration date in 2032, not taking into account extension under applicable laws. In consideration for the rights to abaloparatide and in recognition of certain milestones having been met to date, we have paid to Ipsen an aggregate amount of$1.0 million. The license agreement further requires us to make payments upon the achievement of certain future regulatory and commercial milestones, includingupon acceptance of an NDA submission for review by the FDA. The range of milestone payments that could be paid under the agreement is €10.0 million to€36.0 million ($10.9 million to $39.1 million). Should abaloparatide be approved and subsequently commercialized, we will be obligated to pay to Ipsen a fixedfive percent royalty based on net sales of the product by us or our sublicensees on a country-by-country basis until the later of the last to expire of the licensedpatents or for a period of 10 years after the first commercial sale in such country. The date of the last to expire of the abaloparatide patents licensed from or co-owned with Ipsen, barring any extension thereof, is expected to be March 26, 2028. In the event that we sublicense abaloparatide to a third party, we are obligatedto pay a percentage of certain payments received from such sublicensee (in lieu of milestone payments not achieved at the time of such sublicense). The applicablepercentage is in the low double digit range. In addition, if we or our sublicensees commercialize a product that includes a compound discovered by us based on orderived from confidential Ipsen know-how, we will be obligated to pay to Ipsen a fixed low single digit royalty on net sales of such product on a country-by-country basis until the later of the last to expire of licensed patents that cover such product or for a period of 10 years after the first commercial sale of such productin such country. The license agreement contains other customary clauses and terms as are common in similar agreements in the industry. Prior to executing the license agreement for abaloparatide with us, Ipsen licensed the Japanese rights for abaloparatide to Teijin Limited, or Teijin, a Japanesepharmaceutical company. Teijin has completed a Phase 2 clinical study of abaloparatide in Japan for the treatment of postmenopausal osteoporosis.RAD1901 We exclusively licensed the worldwide rights to RAD1901 from Eisai Co. Ltd., or Eisai. Our license with Eisai did not originally include rights for Japan,however, on March 9, 2015, we entered85Table of Contentsinto an amendment to the Eisai Agreement in which Eisai granted us an exclusive right and license to research, develop, manufacture and commercialize RAD1901in Japan. In consideration for the rights to RAD1901 in Japan, we paid Eisai an initial license fee of $0.4 million upon execution of the amendment, which wasexpensed during the three months ended March 31, 2015. In consideration for the rights to RAD1901 and in recognition of certain milestones having been met to date, we have paid to Eisai an aggregate amount of$1.9 million. The range of milestone payments that could be paid under the agreement is $1.0 million to $20.0 million. The license agreement further requires us tomake payments upon the achievement of certain future clinical and regulatory milestones. Should RAD1901 be approved and subsequently becomecommercialized, we will be obligated to pay to Eisai a royalty in a variable mid-single digit range based on net sales of the product on a country-by-country basisfor a period that expires on the later of (1) the date the last remaining valid claim in the licensed patents expires, lapses or is invalidated in that country, the productis not covered by data protection clauses, and the sales of lawful generic version of the product account for more than a specified percentage of the total sales of allpharmaceutical products containing the licensed compound in that country; or (2) a period of 10 years after the first commercial sale of the licensed products insuch country, unless it is sooner terminated. The latest valid claim is expected to expire, barring any extension thereof, on August 18, 2026. The royalty rate shallthen be subject to reduction and the royalty obligation will expire at such time as sales of lawful generic version of such product account for more than a specifiedminimum percentage of the total sales of all products that contain the licensed compound. We were also granted the right to grant sublicenses with prior writtenapproval from Eisai. If we sublicense RAD1901 to a third party, we will be obligated to pay Eisai, in addition to the milestones referenced above, a fixed lowdouble digit percentage of certain fees we receive from such sublicensee and royalties in a variable mid-single digit range based on net sales of the sublicensee. Thelicense agreement contains other customary clauses and terms as are common in similar agreements in the industry.Net Operating Loss Carryforwards As of December 31, 2015, we had federal and state net operating loss carryforwards of approximately $419.5 million and $323.0 million, respectively, the useof which may be limited, as described below. If not utilized, the net operating loss carryforwards will expire at various dates through 2035. Under Section 382 of the Code, substantial changes in our ownership may limit the amount of net operating loss carryforwards that could be used annually inthe future to offset taxable income. Specifically, this limitation may arise in the event of a cumulative change in ownership of our company of more than 50%within a three-year period. Any such annual limitation may significantly reduce the utilization of the net operating loss carryforwards before they expire. Theprivate placements and other transactions that have occurred since our inception, may have triggered an ownership change pursuant to Section 382, which couldlimit the amount of net operating loss carryforwards that could be utilized annually in the future to offset taxable income, if any. Any such limitation, whether asthe result of prior private placements, sales of common stock by our existing stockholders or additional sales of common stock by us, could have a material adverseeffect on our results of operations in future years. We are in the process of completing a study to assess whether an ownership change has occurred, or whetherthere have been multiple ownership changes since our inception. In each period since our inception, we have recorded a valuation allowance for the full amount ofour deferred tax asset, as the realization of the deferred tax asset is uncertain. As a result, we have not recorded any federal or state income tax benefit in ourstatement of operations.86Table of ContentsOff-Balance Sheet Arrangements We do not have any off-balance sheet arrangements or any relationships with unconsolidated entities of financial partnerships, such as entities often referred toas structured finance or special purpose entities.Accounting Standards Updates For a discussion of recent accounting standards updates, see note 2 to our consolidated financial statements included in this Annual Report.87Table of ContentsITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK. We are exposed to market risk related to changes in the dollar/euro exchange rate because a portion of our development costs are denominated in euros. We donot hedge our foreign currency exchange rate risk. However, an immediate 10 percent adverse change in the dollar/euro exchange rate would not have a materialeffect on financial results. We are exposed to market risk related to changes in interest rates. As of December 31, 2015, we had cash, cash equivalents and short-term marketablesecurities of $473.3 million, consisting of cash, money market funds, domestic corporate debt securities, domestic corporate commercial paper, and asset-backedsecurities. This exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because ourinvestments are in marketable securities. Due to the short-term duration of our investment portfolio and the low risk profile of our investments, an immediate 10%change in interest rates would not have a material effect on the fair market value of our portfolio. We generally have the ability to hold our investments untilmaturity, and therefore we would not expect our operating results or cash flows to be affected to any significant degree by the effect of a change in market interestrates on our investments. We carry our investments based on publicly available information. As of December 31, 2015, we do not have any hard to valueinvestment securities or securities for which a market is not readily available or active. We are not subject to significant credit risk as this risk does not have the potential to materially impact the value of assets and liabilities.88Table of ContentsITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA. FINANCIAL STATEMENTS Radius Health, Inc. Index to Consolidated Financial Statements89 PAGE Report of Independent Registered Public Accounting Firm 90 Consolidated Balance Sheets as of December 31, 2015 and 2014 91 Consolidated Statements of Operations and Comprehensive Loss for the years ended December 31, 2015, 2014 and2013 92 Consolidated Statements of Convertible Preferred Stock, Redeemable Convertible Preferred Stock and Stockholders'Equity (Deficit) for the years ended December 31, 2015, 2014 and 2013 93 Consolidated Statements of Cash Flows for the years ended December 31, 2015, 2014 and 2013 95 Notes to Consolidated Financial Statements 96 Table of ContentsReport of Independent Registered Public Accounting FirmThe Board of Directors and Shareholders of Radius Health, Inc. We have audited the accompanying consolidated balance sheets of Radius Health, Inc. as of December 31, 2015 and 2014, and the related consolidatedstatements of operations and comprehensive loss, convertible preferred stock, redeemable convertible preferred stock and stockholders' equity (deficit), and cashflows for each of the three years in the period ended December 31, 2015. These financial statements are the responsibility of the Company's management. Ourresponsibility is to express an opinion on these financial statements based on our audits. We conducted our audits in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standards require thatwe plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement. An audit includesexamining, on a test basis, evidence supporting the amounts and disclosures in the financial statements. An audit also includes assessing the accounting principlesused and significant estimates made by management, as well as evaluating the overall financial statement presentation. We believe that our audits provide areasonable basis for our opinion. In our opinion, the financial statements referred to above present fairly, in all material respects, the consolidated financial position of Radius Health, Inc. atDecember 31, 2015 and 2014, and the consolidated results of its operations and its cash flows for each of the three years in the period ended December 31, 2015, inconformity with U.S. generally accepted accounting principles. We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States), Radius Health Inc.'s internalcontrol over financial reporting as of December 31, 2015, based on criteria established in Internal Control—Integrated Framework issued by the Committee ofSponsoring Organizations of the Treadway Commission (2013 framework) and our report dated February 25, 2016 expressed an unqualified opinion thereon.Boston, Massachusetts February 25, 201690 /s/ Ernst & Young LLPTable of ContentsRadius Health, Inc. Consolidated Balance Sheets (In thousands, except share and per share amounts) See accompanying notes to consolidated financial statements.91 December 31, 2015 December 31, 2014 ASSETS Current assets: Cash and cash equivalents $159,678 $28,518 Marketable securities 313,661 76,758 Prepaid expenses and other current assets 6,969 2,057 Total current assets 480,308 107,333 Property and equipment, net 1,897 842 Other assets 260 242 Total assets $482,465 $108,417 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $6,228 $2,292 Accrued expenses and other current liabilities 14,952 18,267 Total current liabilities 21,180 20,559 Note payable, net of current portion and discount — 24,394 Total liabilities $21,180 $44,953 Commitments and contingencies Stockholders' equity: Common stock, $.0001 par value; 200,000,000 shares authorized, 42,984,243 shares and32,924,535 shares issued and outstanding at December 31, 2015 and 2014, respectively 4 3 Additional paid-in-capital 907,040 407,720 Accumulated other comprehensive income (loss) 5 (21)Accumulated deficit (445,764) (344,238)Total stockholders' equity 461,285 63,464 Total liabilities and stockholders' equity $482,465 $108,417 Table of ContentsRadius Health, Inc. Consolidated Statements of Operations and Comprehensive Loss (In thousands, except share and per share amounts) See accompanying notes to consolidated financial statements.92 December 31, 2015 2014 2013 OPERATING EXPENSES: Research and development $68,280 $45,719 $60,536 General and administrative 30,797 13,674 6,829 Loss from operations (99,077) (59,393) (67,365)OTHER (EXPENSE) INCOME: Other (expense) income, net (35) (510) 9,085 Loss on retirement of note payable (1,572) (203) — Interest income 1,043 94 30 Interest expense (1,885) (2,467) (2,440)NET LOSS $(101,526)$(62,479)$(60,690)OTHER COMPREHENSIVE LOSS, NET OF TAX: Unrealized gain (loss) from available-for-sale securities 26 (21) — COMPREHENSIVE LOSS $(101,500)$(62,500)$(60,690)LOSS ATTRIBUTABLE TO COMMON STOCKHOLDERS—BASIC ANDDILUTED (Note 12) $(101,526)$(71,479)$(78,161)LOSS PER SHARE: Basic and diluted $(2.56)$(4.04)$(203.91)WEIGHTED AVERAGE SHARES: Basic and diluted 39,643,099 17,699,487 383,310 Table of ContentsRadius Health, Inc.Consolidated Statements of Convertible Preferred Stock, Redeemable Convertible Preferred Stock and Stockholders' Equity (Deficit)(In thousands, except share and per share amounts)See accompanying notes to consolidated financial statements.93 Convertible Preferred Stock Series B-2 Series B Series A-1 Series A-2 Series A-3 Series A-4 Series A-5 Series A-6 Shares Amount Shares Amount Shares Amount Shares Amount Shares Amount Shares Amount Shares Amount Shares Amount Balance atDecember 31,2012 — — — — 939,612 $71,957 983,208 $86,714 142,227 $11,182 3,998 $271 6,443 $525 — $— Net loss Stock optionsexercised Issuance ofpreferred stock 701,235 41,514 496,111 23,168 Accretion ofdividends onpreferred stock 2,378 6,780 7,263 1,050 Stock-basedcompensationexpense Balance atDecember 31,2013 — $— 701,235 $43,892 939,612 $78,737 983,208 $93,977 142,227 $12,232 3,998 $271 6,443 $525 496,111 $23,168 Net loss Unrealized lossfrom available-for-salesecurities Issuance ofpreferred stock 448,060 26,152 186,847 10,109 Accretion ofdividends onpreferred stock 685 1,515 3,084 3,246 470 Issuance ofwarrants Exercise ofwarrants Stock optionsexercised Stock-basedcompensationexpense Issuance ofcommon stock,net Conversion ofconvertiblepreferred stockinto commonstock (448,060) (26,837) (701,235)$(45,407) (939,612) (81,821) (983,208) (97,223) (142,227) (12,702) (3,998) (271) (6,443) (525) (682,958) (33,277)Reclassificationof warrantliability toadditional paidin capital Balance atDecember 31,2014 — $— — $— — $— — $— — $— — $— — $— — $— Net loss Unrealized gainfrom available-for-salesecurities Exercise ofwarrants Exercise ofoptions Stock-basedcompensationexpense Issuance ofcommon stock,net Balance atDecember 31,2015 — $— — $— — $— — $— — $— — $— — $— — $— Table of ContentsRadius Health, Inc. Consolidated Statements of Convertible Preferred Stock, Redeemable Convertible Preferred Stock and Stockholders' Equity (Deficit) (Continued) (In thousands, except share and per share amounts) See accompanying notes to consolidated financial statements.94 Stockholders' Equity (Deficit) Common Stock Additional Paid-In-Capital Accumulated Other ComprehensiveIncome (Loss) AccumulatedDeficit TotalStockholders' (Deficit) Equity Shares Amount Amount Amount Amount Amount Balance at December 31, 2012 380,328 $— $— $— $(200,661)$(200,661)Net loss (60,690) (60,690)Stock options exercised 5,336 13 13 Issuance of preferred stock — Accretion of dividends on preferred stock (1,521) (15,950) (17,471)Stock-based compensation expense 1,508 1,508 Balance at December 31, 2013 385,664 $— $— $— $(277,301)$(277,301)Net loss (62,479) (62,479)Unrealized loss from available-for-sale securities (21) (21)Issuance of preferred stock — Accretion of dividends on preferred stock (4,542) (4,458) (9,000)Issuance of warrants 41 41 Exercise of warrants 20,435 — Stock options exercised 49,382 170 170 Stock-based compensation expense 7,070 7,070 Issuance of common stock, net 10,141,268 1 103,803 103,804 Conversion of convertible preferred stock intocommon stock 22,327,786 2 298,061 298,063 Reclassification of warrant liability to additionalpaid in capital 3,117 3,117 Balance at December 31, 2014 32,924,535 $3 $407,720 $(21)$(344,238)$63,464 Net loss (101,526) (101,526)Unrealized gain from available-for-sale securities 26 26 Exercise of warrants 529,862 — Exercise of options 267,684 2,337 2,337 Stock-based compensation expense 14,734 14,734 Issuance of common stock, net 9,262,162 1 482,249 482,250 Balance at December 31, 2015 42,984,243 $4 $907,040 $5 $(445,764)$461,285 Table of ContentsRadius Health, Inc. Consolidated Statements of Cash Flows (In thousands) See accompanying notes to consolidated financial statements.95 Year Ended December 31, 2015 2014 2013 CASH FLOWS USED IN OPERATING ACTIVITIES: Net loss $(101,526)$(62,479)$(60,690)Adjustments to reconcile net loss to net cash used in operating activities: Depreciation and amortization 176 77 27 Amortization of premium (accretion of discount) marketable securities, net 1,714 429 27 Stock-based compensation expense 14,734 7,070 1,508 Research and development expense settled in stock — 2,717 13,118 Change in fair value of other current assets, warrant liability and other liability — 505 (9,087)Non-cash interest 183 295 387 Loss on retirement of note payable 1,572 57 — Changes in operating assets and liabilities: Prepaid expenses and other current assets (4,914) (1,639) 1,721 Other long-term assets (108) (105) — Accounts payable 3,936 1,991 (250)Accrued expenses and other current liabilities (2,870) 2,737 8,222 Net cash used in operating activities (87,103) (48,345) (45,017)CASH FLOWS (USED IN) PROVIDED BY INVESTING ACTIVITIES: Purchases of property and equipment (1,231) (857) (2)Purchases of marketable securities (579,088) (97,678) (17,070)Sales and maturities of marketable securities 340,497 20,470 21,043 Net cash (used in) provided by investing activities (239,822) (78,065) 3,971 CASH FLOWS PROVIDED BY FINANCING ACTIVITIES: Proceeds from exercise of stock options 2,337 170 13 Net proceeds from the issuance of preferred stock, net — 27,368 42,870 Proceeds from note payable, net — 24,555 — Proceeds from issuance of common stock, net 482,250 103,804 — Deferred financing costs — (116) — Payments on note payable (25,000) (13,156) (8,187)Fee for early prepayment of note payable (1,502) — — Net cash provided by financing activities 458,085 142,625 34,696 NET INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS 131,160 16,215 (6,350)CASH AND CASH EQUIVALENTS AT BEGINNING OF YEAR 28,518 12,303 18,653 CASH AND CASH EQUIVALENTS AT END OF YEAR $159,678 $28,518 $12,303 SUPPLEMENTAL DISCLOSURES: Cash paid for interest $1,490 $1,971 $1,796 NON-CASH FINANCING ACTIVITIES: Accretion of dividends on preferred stock $— $9,000 $17,471 Reclassification of preferred stock to common stock $— $298,063 $— Fair value of series A-6 convertible preferred stock issued as settlement of liability $— $10,109 $23,168 Fair value of warrants issued $— $1,552 $1,356 Table of ContentsRadius Health, Inc. Notes to Consolidated Financial Statements 1. Nature of Business Radius Health, Inc. ("Radius" or the "Company") is a science-driven biopharmaceutical company that is committed to developing innovative therapeutics inthe areas of osteoporosis, oncology and endocrine diseases. The Company's lead product candidate, the investigational drug abaloparatide for subcutaneousinjection ("abaloparatide-SC"), has completed Phase 3 development for potential use in the reduction of fracture risk in postmenopausal women with osteoporosisand is currently under regulatory review in Europe. The Company's clinical pipeline also includes an investigational abaloparatide transdermal patch("abaloparatide-TD") for potential use in osteoporosis and the investigational drug RAD1901 for potential use in hormone-driven, or hormone-resistant, breastcancer, and vasomotor symptoms in postmenopausal women. The Company's preclinical pipeline includes RAD140, a non-steroidal selective androgen receptormodulator, under investigation for potential applications in oncology and multiple conditions where androgen modulation may offer therapeutic benefit. The Company is subject to the risks associated with emerging companies with a limited operating history, including dependence on key individuals, adeveloping business model, the necessity of securing regulatory approval to market its investigational product candidates, market acceptance of the Company'sinvestigational product candidates following receipt of regulatory approval, competition for its investigational product candidates following receipt of regulatoryapproval, and the continued ability to obtain adequate financing to fund the Company's future operations. The Company has incurred losses and expects to continueto incur additional losses for the foreseeable future. As of December 31, 2015, the Company had an accumulated deficit of $445.8 million, and total cash, cashequivalents and marketable securities of $473.3 million. Based upon its cash, cash equivalents and marketable securities balance as of December 31, 2015, the Company believes that, prior to the consideration ofrevenue from the potential future sales of any of its investigational products that may receive regulatory approval or proceeds from partnership activities, it hassufficient capital to fund its development plans, U.S. commercial scale-up and other operational activities into 2018. The Company expects to finance the futuredevelopment costs of its clinical product portfolio with its existing cash and cash equivalents and marketable securities, or through strategic financing opportunitiesthat could include, but are not limited to partnering or other collaboration agreements, future offerings of its equity, or the incurrence of debt. However, there is noguarantee that any of these strategic or financing opportunities will be executed or executed on favorable terms, and some could be dilutive to existingstockholders. If the Company fails to obtain additional future capital, it may be unable to complete its planned preclinical and clinical trials and obtain approval ofcertain investigational product candidates from the U.S. Food and Drug Administration or foreign regulatory authorities.2. Summary of Significant Accounting Policies Basis of Presentation —The consolidated financial statements include the accounts of the Company and its wholly-owned subsidiary, Radius Health SecuritiesCorporation. All material intercompany balances and transactions have been eliminated in consolidation. Reverse Stock Split —On April 24, 2014, the Company effected a reverse stock split of the Company's common stock. The number of authorized shares of theCompany's common stock and the par value did not change. Pursuant to the stock split, every 2.28 shares of the Company's issued and outstanding common stockwere automatically combined into one issued and outstanding share of the96Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)2. Summary of Significant Accounting Policies (Continued)Company's common stock. All shares and per share amounts in the financial statements and accompanying notes have been retroactively adjusted to give effect tothe reverse stock split. Use of Estimates —The preparation of consolidated financial statements in conformity with accounting principles generally accepted in the United States("GAAP") requires the Company's management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements andaccompanying notes. Actual results could differ from those estimates. The Company considers events or transactions that occur after the balance sheet date butbefore the consolidated financial statements are issued as additional evidence for certain estimates or to identify matters that require additional disclosure.Subsequent events have been evaluated up to the date of issuance of these consolidated financial statements. Cash Equivalents —The Company considers all highly liquid investment instruments with an original maturity when purchased of three months or less to becash equivalents. Money market funds represents a majority of the cash equivalent balance at December 31, 2015 and 2014. Marketable Securities —All investment instruments with an original maturity date, when purchased, in excess of three months have been classified as currentmarketable securities. The Company classifies securities that are available to fund current operations as current assets. These marketable securities are classified asavailable-for-sale and are carried at fair value. Unrealized gains and losses, if any, are included within other comprehensive (loss) income within stockholders'equity (deficit). The amortized cost of debt securities in this category is adjusted for amortization of premiums and accretion of discounts to maturity. Suchamortization is included in interest income. Realized gains and losses on available-for-sale securities are included in interest income. The cost of securities sold isbased on the specific identification method. The Company periodically reviews the portfolio of securities to determine whether an other-than-temporaryimpairment has occurred. No such losses have occurred to date. There were no realized gains or losses on the sale of securities for the years ended December 31,2015 and 2014. Fair Value Measurements —The Company determines the fair market values of its financial instruments based on the fair value hierarchy, which requires anentity to maximize the use of observable inputs and minimize the use of unobservable inputs when measuring fair value. The following are three levels of inputsthat may be used to measure fair value: Concentrations of Credit Risk and Off-Balance-Sheet Risk —Financial instruments that potentially subject the Company to credit risk primarily consist of cashand cash equivalents and available-for-sale marketable securities. The Company mitigates its risk with respect to cash and cash equivalents and97 Level 1 Quoted prices in active markets for identical assets or liabilities that the Company has the ability to access at the measurement date. Level 2 Observable inputs other than Level 1 prices such as quoted prices for similar assets or liabilities; quoted prices in markets that are not active; or otherinputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities. Level 3 Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities.Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)2. Summary of Significant Accounting Policies (Continued)marketable securities by maintaining its deposits and investments at high-quality financial institutions. The Company invests any excess cash in money marketfunds and other securities, and the management of these investments is not discretionary on the part of the financial institution. The Company has no significantoff-balance-sheet risks such as foreign exchange contracts, option contracts, or other hedging arrangements. Inventory —The Company capitalizes inventories produced in preparation for initiating sales of a drug candidate when the related drug candidate is approvedor considered to have a high likelihood of regulatory approval and the related costs are expected to be recoverable through sales of the inventories. An assessmentof inventory capitalization begins either on or after the date a New Drug Application is accepted for filing by the U.S. Food and Drug Administration, or aninternational equivalent. Determining whether or not to continue to record the commercial supply costs related to a product candidate as research and developmentexpenses or to capitalize these costs as inventory involves significant judgment. There were no capitalized inventories as of December 31, 2015 and 2014. Property and Equipment —Property and equipment are recorded at cost and depreciated using the straight-line method over the estimated useful lives of therespective assets. Research and Development Costs —The Company accounts for research and development costs by expensing such costs to operations as incurred. Researchand development costs primarily consist of clinical testing costs, including payments made to contract research organizations, personnel costs, outsourced researchactivities, laboratory supplies, and license fees. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred and capitalized.The capitalized amounts are expensed as the related goods are delivered or the services are performed. Licensing Agreements —Costs associated with licensing early stage technology are expensed as incurred, and are included in research and developmentexpenses. Impairment of Long-Lived Assets —The Company evaluates long-lived assets for potential impairment when there is evidence that events or changes incircumstances have occurred that indicate that the carrying amount of a long-lived asset may not be recovered. Recoverability of these assets is assessed based onthe undiscounted expected future cash flows from the assets, considering a number of factors, including past operating results, budgets and economic projections,market trends, and product development cycles. Impairment in the carrying value of each asset is assessed when the undiscounted expected future cash flowsderived from the asset are less than its carrying value. An impairment loss would be recognized in an amount equal to the excess of the carrying amount over the undiscounted expected future cash flows. Noimpairment charges have been recognized since the Company's inception. Segment Information —Operating segments are defined as components of an enterprise engaged in business activities for which discrete financial informationis available and regularly reviewed by the chief decision maker in determining how to allocate resources and in assessing performance. The Company views itsoperations and manages its business as one operating segment and operates in one geographic area.98Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)2. Summary of Significant Accounting Policies (Continued) Income Taxes —The Company recognizes deferred tax assets and liabilities for the future tax consequences attributable to differences between the financialstatement carrying amounts of existing assets and liabilities and their respective tax basis, as well as operating loss and tax credit carryforwards. The Companymeasures deferred tax assets and liabilities using enacted tax rates expected to apply to taxable income in the years in which those temporary differences andcarryforwards are expected to be recovered or settled. Deferred tax assets are reduced by a valuation allowance to reflect the uncertainty associated with theirultimate realization. The effect on deferred tax assets and liabilities as a result of a change in tax rates is recognized as income in the period that includes theenactment date. The Company uses judgment to determine the recognition threshold and measurement attribute for financial statement recognition and measurement of a taxposition taken or expected to be taken in a tax return. Any material interest and penalties related to unrecognized tax benefits are recognized in income tax expense. Due to uncertainty surrounding the realization of the favorable tax attributes in future tax returns the Company has recorded a full valuation allowance againstotherwise realizable net deferred tax assets as of December 31, 2015 and 2014. Financial Instruments Indexed to and Potentially Settled in the Company's Common Stock —The Company evaluates all financial instruments issued inconnection with its debt borrowings and equity offerings when determining the proper accounting treatment for such instruments in the Company's consolidatedfinancial statements. The Company considers a number of generally accepted accounting principles to determine such treatment and evaluates the features of theinstrument to determine the appropriate accounting treatment. The Company utilizes the Black-Scholes method or other appropriate methods to determine the fairvalue of its derivative financial instruments. Key valuation factors in determining the fair value include, but are not limited to, the current stock price as of the dateof measurement, the exercise price, the remaining contractual life, expected volatility for the instrument and the risk-free interest rate. For financial instruments thatare determined to be classified as liabilities on the balance sheet, changes in fair value are recorded as a gain or loss in the Company's statement of operations, withthe corresponding amount recorded as an adjustment to the liability on its balance sheet. Stock-Based Compensation-Options —The Company measures stock-based compensation cost at the accounting measurement date based on the fair value ofthe option, and recognizes the expense related to awards to employees on a straight-line basis over the requisite service period of the option, which is typically thevesting period. The Company estimates the fair value of each option using the Black-Scholes option pricing model that takes into account the fair value of its common stock,the exercise price, the expected life of the option, the expected volatility of its common stock, expected dividends on its common stock, and the risk-free interestrate over the expected life of the option. Due to the limited trading history of the Company's common stock since its June 2014 initial public offering, the Companyuses the simplified method described in the SEC's Staff Accounting Bulletin No. 107, Share-Based Payment, to determine the expected life of the option grants.The estimate of expected volatility is based on a review of the historical volatility of similar publicly held companies in the biotechnology field over a periodcommensurate with the option's expected term. The Company has never declared or paid any cash dividends on its common stock and does not expect to do so inthe foreseeable future. Accordingly, it99Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)2. Summary of Significant Accounting Policies (Continued)uses an expected dividend yield of zero. The risk-free rate is based on the U.S. Treasury yield curve in effect at the time of grant valuation for a periodcommensurate with the option's expected term. These assumptions are highly subjective and changes in them could significantly impact the value of the option andhence the related compensation expense. The Company applies an estimated forfeiture rate to current period expense to recognize compensation expense only for those awards expected to vest.Forfeitures are estimated based upon historical data, adjusted for known trends, and the Company will adjust the estimate of forfeitures if actual forfeitures differ orare expected to differ from such estimates. Subsequent changes in estimated forfeitures are recognized through a cumulative adjustment in the period of change andalso will impact the amount of stock-based compensation expense in future periods. Stock-based compensation expense recognized for options granted to consultants is also based upon the fair value of the options issued, as determined by theBlack-Scholes option pricing model and recognized on an accelerated basis. However, the unvested portion of such option grants is re-measured at each reportingperiod, until such time as the option is fully vested. Stock-Based Compensation-Performance Units —The Company measures stock-based compensation cost at the accounting measurement date based on thefair value of the performance unit grant, and recognizes the expense over the derived service period of the performance units. The Company estimates the fair value of each grant using a Monte Carlo simulation analysis that takes into account the forecasted price of its common stock,historical volatility of its common stock, risk-free rate as of valuation date, price of its common stock as of the grant date and the trigger for the performancecondition to be met. The derived service period for each grant is calculated using a Monte Carlo simulation analysis. Net Loss Per Common Share —Net loss per common share is calculated using the two-class method, which is an earnings allocation formula that determinesnet loss per share for the holders of the Company's common shares and participating securities. Prior to the initial public offering, all of the Company's series ofpreferred stock contained participation rights in any dividend paid by the Company and were deemed to be participating securities. Net income available tocommon shareholders and participating preferred shares was allocated to each share on an as-converted basis as if all of the earnings for the period had beendistributed. The participating securities do not include a contractual obligation to share in losses of the Company and are not included in the calculation of net lossper share in the periods that have a net loss. Diluted net income per share is computed using the more dilutive of (a) the two-class method, or (b) the if-converted method. Prior to the initial publicoffering, the Company allocated net income first to preferred stockholders based on dividend rights and then to common and preferred stockholders based onownership interests. The weighted-average number of common shares outstanding gives effect to all potentially dilutive common equivalent shares, includingoutstanding stock options, warrants, and, prior to the Company's initial public offering, potential issuance of stock upon the issuance of the Company's series A-6convertible preferred stock ("Series A-6") as settlement of the liability to Nordic Bioscience ("Nordic"). Common equivalent shares are excluded from thecomputation of diluted net income per share if their effect is anti-dilutive.100Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)2. Summary of Significant Accounting Policies (Continued) Comprehensive Income (Loss) —Comprehensive income (loss) refers to revenues, expenses, gains and losses that are excluded from net income (loss), asthese amounts are recorded directly as an adjustment to stockholders' equity (deficit), net of tax. The Company's other comprehensive (loss) income is comprised ofunrealized gains (losses) on its available-for-sale marketable securities. Accounting Standards Updates —In August 2014, the Financial Accounting Standards Board ("FASB") issued Accounting Standards Update No. 2014-15,Disclosures of Uncertainties about an Entity's Ability to Continue as a Going Concern ("ASU 2014-15"). ASU 2014-15 provides guidance in GAAP aboutmanagement's responsibility to evaluate whether there is substantial doubt about an entity's ability to continue as a going concern and to provide related footnotedisclosures. The amendments under ASU 2014-15 are effective for interim and annual fiscal periods beginning after December 15, 2016, with early adoptionpermitted. The Company does not expect the adoption of ASU 2014-15 to have a material impact on its results of operations, financial position or cash flows. In January 2015, the FASB issued Accounting Standards Update No. 2015-01, Income Statement—Extraordinary and Unusual Items (Subtopics 225-20)("ASU 2015-01"). ASU 2015-01 eliminates the concept of extraordinary items from GAAP. The amendments under ASU 2015-01 are effective for interim andannual fiscal periods beginning after December 15, 2015, with early adoption permitted. The Company does not expect the adoption of ASU 2015-01 to have amaterial impact on its results of operations, financial position or cash flows. In April 2015, the FASB issued Accounting Standards Update No. 2015-03, Interest—Imputation of Interest (Subtopic 835-30) ("ASU 2015-03"). ASU 2015-03 requires that, instead of presentation as an asset, debt issuance costs be presented in the balance sheet as a direct deduction from the carrying amount of that debtliability, consistent with debt discounts. The amendments under ASU 2015-03 are effective for interim and annual fiscal periods beginning after December 15,2015, with early adoption permitted, and should be applied on a retrospective basis. The Company does not expect the adoption of ASU 2015-03 to have a materialimpact on its results of operations, financial position or cash flows. In April 2015, the FASB issued Accounting Standards Update No. 2015-05, Intangibles-Goodwill and Other-Internal-Use Software (Subtopic 350-40) ("ASU2015-05"). ASU 2015-05 updates guidance regarding accounting for cloud computing arrangements. The amendments under ASU 2015-05 are effective for interimand annual fiscal periods beginning after December 15, 2015, with early adoption permitted. The Company does not expect the adoption of ASU 2015-05 to have amaterial impact on its results of operations, financial position or cash flows. In November 2015, the FASB issued Accounting Standards Update No. 2015-17, Income Taxes (Topic 740) ("ASU 2015-17"). ASU 2015-17 requiresdeferred tax liabilities and assets to be classified as noncurrent in a classified statement of financial position, instead of separating deferred income tax liabilitiesand assets into current and noncurrent amounts. The amendments under ASU 2015-17 apply to all entities that present a classified statement of financial positionand are effective, for public entities, for financial statements issued for annual periods beginning after December 15, 2016, and interim periods within those annualperiods, with early adoption permitted for all entities as of the beginning of an interim or annual reporting period. The Company elected to early adopt ASU 2015-17 effective December 31, 2015 on a prospective basis. Adoption of this ASU resulted in a reclassification of our net current deferred tax asset to the net non-current deferred tax asset in our Consolidated Balance Sheet as of December 31, 2015. No prior periods were retrospectively adjusted.101Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)2. Summary of Significant Accounting Policies (Continued) In January 2016, the FASB issued Accounting Standards Update No. 2016-01, Financial Statements—Overall (Subtopics 825-10) ("ASU 2016-01"). ASU2016-01 provides updated guidance on the recognition and measurement of financial assets and financial liabilities that will supersede most current guidance. ASU2016-01 primarily affects the accounting for equity investments, financial liabilities under the fair value option, and the presentation and disclosure requirementsfor financial instruments. The amendments in ASU 2016-01 supersede the guidance to classify equity securities with readily determinable fair values into differentcategories and require equity securities to be measured at fair value with changes in the fair value recognized through net income. The amendments under ASU2016-01 are effective, for public business entities, for periods beginning after December 15, 2017, including interim periods within those fiscal years, and withearly adoption permitted. The Company does not expect the adoption of ASU 2016-01 to have a material impact on its results of operations, financial position orcash flows.3. Marketable Securities Available-for-sale marketable securities and cash and cash equivalents consist of the following (in thousands):102 December 31, 2015 Amortized Cost Value Gross Unrealized Gains Gross Unrealized Losses Fair Value Cash and cash equivalents: Cash $2,934 $— $— $2,934 Money market 83,257 — — 83,257 Domestic corporate commercial paper 39,984 — — 39,984 Government-sponsored enterprise debt securities 15,996 — — 15,996 Domestic corporate debt securities 10,007 — — 10,007 Asset-backed securities 7,500 — — 7,500 Total $159,678 $— $— $159,678 Marketable securities: Domestic corporate debt securities $173,142 $— $(107)$173,035 Domestic corporate commercial paper 84,004 154 — 84,158 Asset-backed securities 56,510 1 (43) 56,468 Total $313,656 $155 $(150)$313,661 Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)3. Marketable Securities (Continued) There were no debt securities that had been in an unrealized loss position for more than 12 months as of December 31, 2015 or December 31, 2014. Therewere 57 debt securities in an unrealized loss position for less than 12 months at December 31, 2015 and there were 34 debt securities that had been in an unrealizedloss position for less than 12 months at December 31, 2014. The aggregate unrealized loss on these securities as of December 31, 2015 and 2014 was less than$150 thousand and $34 thousand, respectively, and the fair value was $225.7 million and $68.9 million, respectively. The Company considered the decline inmarket value for these securities to be primarily attributable to current economic conditions. As it was not more likely than not that the Company would be requiredto sell these securities before the recovery of their amortized cost basis, which may be maturity, the Company did not consider these investments to be other-than-temporarily impaired as of December 31, 2015 and 2014. As of December 31, 2015 and 2014, marketable securities consisted of investments that mature within one year.103 December 31, 2014 Amortized Cost Value Gross Unrealized Gains Gross Unrealized Losses Fair Value Cash and cash equivalents: Cash $1,519 $— $— $1,519 Money market funds 23,994 — — 23,994 Domestic corporate debt securities 3,005 — — 3,005 Total $28,518 $— $— $28,518 Marketable securities: Domestic corporate debt securities 69,542 — (33) 69,509 Domestic corporate commercial paper 7,237 12 — 7,249 Total $76,779 $12 $(33)$76,758 Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)4. Property and Equipment Property and equipment consists of the following (in thousands): During the year ended December 31, 2014, the Company retired $0.7 million of property and equipment. The retirement was primarily due to the disposal ofleasehold improvements and other property as a result of the Company's office relocation. All assets were fully depreciated prior to retirement.5. Accrued Expenses and Other Current Liabilities Accrued expenses consist of the following (in thousands):6. Loan and Security Agreement On May 23, 2011, the Company entered into a loan and security agreement with Oxford Finance LLC ("Oxford") and General Electric Capital Corporation("GECC") pursuant to which Oxford and GECC agreed to lend the Company up to $25.0 million. Upon entering into the loan and104 December 31, Estimated Useful Life (In Years) 2015 2014 Furniture and fixtures 5 $314 $167 Computer equipment and software 3 479 230 Manufacturing equipment 10 1,127 598 Leasehold improvements Shorter of useful life or remaining leaseterm 322 16 2,242 1,011 Less accumulated depreciation andamortization (345) (169)Property and equipment, net $1,897 $842 December 31, 2015 2014 Research costs—Nordic(1) $2,898 $11,536 Research costs—other 5,178 3,336 Payroll and employee benefits 3,330 1,659 Professional fees 3,546 1,304 Accrued interest on notes payable — 234 Other — 198 Total accrued expenses and other current liabilties $14,952 $18,267 (1)Includes amounts accrued ratably over the estimated per patient treatment period under the Nordic Work Statement NB-1 andWork Statement NB-3. Amounts do not include pass-through costs which are expensed as incurred or upon delivery. See note 10for additional information.Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)6. Loan and Security Agreement (Continued)security agreement, the Company borrowed $6.3 million on May 23, 2011("Term Loan A"), $6.3 million on November 21, 2011 ("Term Loan B") and anadditional $12.5 million on May 29, 2012 ("Term Loan C"). Interest on the outstanding Term Loan A was payable on a monthly basis through and including December 1, 2011. Principal and interest payments on TermLoan A was payable in 36 equal monthly installments beginning December 1, 2011 through November 1, 2014, with a final balloon payment of $0.6 million dueupon maturity on November 22, 2014. Interest was payable on Term Loan A at an annual interest rate of 10.16%. Interest on the outstanding Term Loan B waspayable on a monthly basis through and including June 1, 2012. Principal and interest payments on Term Loan B was payable in 30 equal monthly installmentsbeginning June 1, 2012, through November 1, 2014, with a final balloon payment of $0.6 million due upon maturity on November 22, 2014. Interest was payableon Term Loan B at an annual interest rate of 10%. Interest on Term Loan C was payable on a monthly basis through, and including, November 1, 2012. Principaland interest payments on Term Loan C was payable in 24 monthly installments beginning December 1, 2012, through November 1, 2014 with a final balloonpayment of $1.3 million upon maturity on November 22, 2014. Interest was payable on Term Loan C at an annual interest rate of 10%. On May 30, 2014, the Company entered into a loan and security agreement (the "Credit Facility), with Solar Capital Ltd. ("Solar"), as collateral agent and alender, and Oxford, as a lender (the "Lenders"), pursuant to which Solar and Oxford agreed to make available to the Company $30.0 million in the aggregatesubject to certain conditions to funding. An initial term loan was made on May 30, 2014 in an aggregate principal amount equal to $21.0 million (the "Initial TermLoan"). The Company used approximately $9.3 million of the Initial Term Loan to repay all amounts owed under its loan and security agreement with GECC andOxford. On July 10, 2014, the Company entered into a first amendment to the Credit Facility (the "First Amendment"). The terms of the First Amendment, amongother things, provided the Company with, subject to certain customary funding conditions, additional term loans in an aggregate principal amount of $4.0 millionupon the closing of the First Amendment. The Company borrowed the additional $4.0 million on July 10, 2014. The Company had been required to make interest-only payments through December 1, 2015, and beginning on January 1, 2016, it would have been required tomake payments of principal and accrued interest in equal monthly installments over a term of 30 months. The Initial Term Loan bore interest per annum at 9.85%plus one-month LIBOR (customarily defined). All principal and accrued interest on the Initial Term Loan had been due on June 1, 2018. On August 4, 2015, the Company prepaid all amounts owed under the Credit Facility and the First Amendment. After consideration of relevant fees requiredunder the Credit Facility and the First Amendment, the total payment amounted to $26.5 million, which resulted in a loss on retirement of $1.6 million during thethird quarter of 2015.7. Stockholders' Equity and Convertible Preferred StockCommon Stock On June 11, 2014, the Company completed its initial public offering whereby the Company sold 6,500,000 shares of common stock at a price of $8.00 pershare. The shares began trading on the105Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)7. Stockholders' Equity and Convertible Preferred Stock (Continued)NASDAQ Global Market on June 6, 2014. In connection with the offering, all outstanding shares of our convertible preferred stock converted into 19,465,132shares of common stock and 2,862,654 shares of common stock were issued in satisfaction of accumulated dividends accrued on the preferred stock. In addition, alloutstanding warrants to purchase shares of series A-1 convertible preferred stock and warrants to purchase shares of series B-2 convertible preferred stock wereconverted into the right to purchase 149,452 shares of common stock and the Company's warrant liability was reclassified to equity. On June 18, 2014 and June 25, 2014, the underwriters purchased an additional 512,744 shares in the aggregate by exercising a portion of the over-allotmentoption granted to them in connection with the initial public offering. As a result of the closing of the initial public offering and subsequent exercise of the over-allotment option, the Company received aggregate proceeds, net of underwriting discounts, commissions and offering costs, of approximately $50.4 million. On October 7, 2014, the Company completed an additional public offering whereby it sold 2,750,000 shares of common stock at a price of $18.25 per share,for aggregate proceeds, net of underwriting discounts, commissions and offering costs, of approximately $46.9 million. On October 7, 2014, the underwriterspurchased an additional 378,524 shares in the aggregate by exercising a portion of the over-allotment option granted to them in connection with the offering. As aresult of the public offering and subsequent exercise of the over-allotment option, the Company received aggregate proceeds, net of underwriting discounts,commissions and offering costs of approximately $53.4 million. On January 28, 2015, the Company completed an additional public offering of 4,000,000 shares of its common stock at a price of $36.75 per share, foraggregate estimated proceeds, net of underwriting discounts, commissions and offering costs, of approximately $137.8 million. Also, on January 28, 2015, theunderwriters purchased an additional 600,000 shares in the aggregate by exercising an option to purchase additional shares that was granted to them in connectionwith the offering. As a result of the public offering and subsequent exercise of the underwriters' option, the Company received aggregate proceeds, net ofunderwriting discounts, commissions and offering costs of approximately $158.4 million. On July 28, 2015, the Company completed an additional public offering of 4,054,054 shares of its common stock at a price of $74.00 per share, for aggregateproceeds, net of underwriting discounts, commissions and offering costs, of approximately $281.5 million. Also, on July 28, 2015, the underwriters purchased anadditional 608,108 shares by exercising an option to purchase additional shares that was granted to them in connection with the offering. As a result of the publicoffering and subsequent exercise of the underwriters' option, the Company received aggregate proceeds, net of underwriting discounts, commissions and estimatedoffering costs of approximately $323.8 million.Preferred Stock On April 23, 2013, the Company entered into a Series B Convertible Preferred Stock and Warrant Purchase Agreement (the "Series B Purchase Agreement"),pursuant to which the Company could raise, at any time on or prior to May 10, 2013, up to approximately $60.0 million through the issuance of (1) up to 980,000shares of its Series B preferred stock (the "Series B") and (2) warrants to acquire up to approximately 1,075,000 shares of its common stock with an exercise priceof $14.004 per share. On April 23, 2013, the Company consummated a first closing under the Series B Purchase Agreement, whereby in exchange for aggregateproceeds of approximately $43.0 million, it issued 700,098 shares of106Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)7. Stockholders' Equity and Convertible Preferred Stock (Continued)Series B and warrants to purchase up to a total of 767,651 shares of its common stock. On May 10, 2013, the Company consummated a second closing under theSeries B Purchase Agreement, whereby in exchange for aggregate proceeds of approximately $0.1 million, it issued 1,137 shares of Series B and warrants topurchase up to a total of 1,246 shares of its common stock. The warrants can be exercised at any time prior to the fifth anniversary of their issuance. On February 14, 2014, the Company entered into a Series B-2 Convertible Preferred Stock and Warrant Purchase Agreement (the "Series B-2 PurchaseAgreement"), pursuant to which the Company was able to raise up to approximately $40.2 million through the issuance of (1) up to 655,000 shares of its preferredstock (the "Series B-2") and (2) warrants to acquire up to 718,201 shares of its common stock with an exercise price of $14.004 per share. In February and March2014, the Company consummated closings under the Series B-2 Purchase Agreement, whereby, in exchange for aggregate gross proceeds to the Company ofapproximately $27.5 million, the Company issued an aggregate of 448,060 shares of Series B-2 and warrants to purchase up to a total of 491,293 shares of itscommon stock. The warrants can be exercised at any time prior to the fifth anniversary of their issuance.8. Fair Value Measurements The following table summarizes the financial instruments measured at fair value on a recurring basis in the accompanying consolidated balance sheets as ofDecember 31, 2015 and December 31, 2014 (in thousands):107 As of December 31, 2015 Level 1 Level 2 Level 3 Total Assets Cash and cash equivalents: Cash $2,934 $— $— $2,934 Money market funds(1) 83,257 — — 83,257 Domestic corporate commercial paper(2) — 39,984 — 39,984 Government-sponsored enterprise debt securities(2) — 15,996 — 15,996 Domestic corporate debt securities(2) — 10,007 — 10,007 Asset-backed securities(2) — 7,500 — 7,500 Total $86,191 $73,487 $— $159,678 Marketable Securities Domestic corporate debt securities(2) $— $173,035 $— $173,035 Domestic corporate commercial paper(2) — 84,158 — 84,158 Asset-backed securities(2) — 56,468 — 56,468 Total $— $313,661 $— $313,661 Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)8. Fair Value Measurements (Continued) 9. License Agreements On September 27, 2005, the Company entered into a license agreement (the "Ipsen Agreement"), as amended, with SCRAS S.A.S, a French corporation onbehalf of itself and its affiliates (collectively, "Ipsen"). Under the Ipsen Agreement, Ipsen granted to the Company an exclusive right and license under certain Ipsencompound technology and related patents to research, develop, manufacture and commercialize certain compounds and related products in all countries, exceptJapan (where the Company does not hold development and commercialization rights) and France (where the Company's commercialization rights are subject tocertain co-marketing and co-promotion rights exercisable by Ipsen, provided that certain conditions included in the Ipsen Agreement have been met). With respectto France, if Ipsen exercises its co-marketing and co-promotion rights, then Ipsen may elect to receive a percentage of the net sales of the products by both partiesin France (subject to a mid-double digit percentage cap), and Ipsen shall bear a corresponding percentage of the costs and expenses incurred by both parties withrespect to such marketing and promotion efforts in France. Ipsen shall also pay the Company a mid-single digit royalty on Ipsen's allocable portion of net sales ofthe product by both parties in France. Abaloparatide is subject to the Ipsen Agreement. Ipsen also granted the Company an exclusive right and license under theIpsen compound technology and related patents to make and have made compounds or product in Japan. Ipsen also granted the Company an exclusive right andlicense under certain Ipsen formulation technology and related patents solely for purposes of enabling the Company to develop, manufacture and commercializecompounds and products covered by the compound technology license in all countries, except Japan (where the Company does not hold commercialization rights)and France (where the Company's commercialization rights are subject to108 As of December 31, 2014 Level 1 Level 2 Level 3 Total Assets Cash and cash equivalents: Cash $1,519 $— $— $1,519 Money market funds(1) 23,994 — — 23,994 Domestic corporate debt securities(2) — 3,005 — 3,005 Total $25,513 $3,005 $— $28,518 Marketable securities: Domestic corporate debt securities(2) $— $69,509 $— $69,509 Domestic corporate commercial paper(2) — 7,249 — 7,249 Total $— $76,758 $— $76,758 (1)Fair value is based upon quoted market prices. (2)Fair value is based upon quoted prices for similar instruments in active markets, quoted prices for identical or similar instruments inmarkets that are not active and model-based valuation techniques for which all significant assumptions are observable in the market or canbe corroborated by observable market data for substantially the full term of the assets. Inputs are obtained from various sources, includingmarket participants, dealers and brokers.Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)9. License Agreements (Continued)certain co-marketing and co-promotion rights exercisable by Ipsen, provided that certain conditions included in the Ipsen Agreement have been met). In consideration for these licenses, the Company made a nonrefundable, non-creditable payment of $0.25 million to Ipsen, which was expensed during 2005.The Ipsen Agreement provides for further payments upon the achievement of certain future regulatory and commercial milestones, including upon acceptance of anew drug application submission for review by the U.S. Food and Drug Administration. The range of milestone payments that could be paid under the agreement is€10.0 million to €36.0 million ($10.9 million to $39.1 million). Should abaloparatide be approved and subsequently commercialized, the Company will beobligated to pay to Ipsen a fixed five percent royalty based on net sales of the product by the Company or its sublicensees on a country-by-country basis until thelater of the last to expire of the licensed patents or for a period of 10 years after the first commercial sale in such country. If the Company sublicenses the rights licensed from Ipsen, then the Company will also be required to pay Ipsen a percentage of certain payments receivedfrom such sublicensee (in lieu of milestone payments not achieved at the time of such sublicense). The applicable percentage is in the low double digit range. Inaddition, if the Company or its sublicensees commercialize a product that includes a compound discovered by it based on or derived from confidential Ipsen know-how, it will be obligated to pay to Ipsen a fixed low single digit royalty on net sales of such product on a country-by-country basis until the later of the last to expireof licensed patents that cover such product or for a period of 10 years after the first commercial sale of such product in such country. In June 2006, the Company entered into a license agreement (the "Eisai Agreement"), with Eisai Co. Ltd., ("Eisai"). Under the Eisai Agreement, Eisai grantedto the Company an exclusive right and license to research, develop, manufacture and commercialize RAD1901 and related products from Eisai in all countries,except Japan. In consideration for the rights to RAD1901, the Company paid Eisai an initial license fee of $0.5 million, which was expensed during 2006. The EisaiAgreement provides for further payments in the range of $1.0 million to $20.0 million (inclusive of the $0.5 million initial license fee), payable upon theachievement of certain clinical and regulatory milestones. On March 9, 2015, the Company entered into an amendment to the Eisai Agreement (the "Eisai Amendment") in which Eisai granted to the Company theexclusive right and license to research, develop, manufacture and commercialize RAD1901 in Japan. In consideration for the rights to RAD1901 in Japan, theCompany paid Eisai an initial license fee of $0.4 million upon execution of the Eisai Amendment, which was recognized as research and development expense in2015. The Eisai Amendment also provides for additional payments, payable upon the achievement of certain clinical and regulatory milestones in Japan. Under the Eisai Agreement, as amended, should a product covered by the licensed technology be commercialized, the Company will be obligated to pay toEisai royalties in a variable mid-single digit range based on net sales of the product on a country-by-country basis. The royalty rate will be reduced, on a country-by-country basis, at such time as the last remaining valid claim in the licensed patents expires, lapses or is invalidated and the product is not covered by dataprotection clauses. In addition, the royalty rate will be reduced, on a country-by-country basis, if, in addition to the conditions specified in the previous sentence,sales of lawful generic versions of such product account for more than a specified minimum percentage of the total sales of all products that contain the licensedcompound during a calendar quarter. The latest valid claim to expire, barring any extension thereof, is expected on August 18, 2026.109Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)9. License Agreements (Continued) The Eisai Agreement, as amended, also grants the Company the right to grant sublicenses with prior written approval from Eisai. If the Company sublicensesthe licensed technology to a third party, the Company will be obligated to pay Eisai, in addition to the milestones referenced above, a fixed low double digitpercentage of certain fees received from such sublicensee and royalties in the low single digit range based on net sales of the sublicensee. The license agreementexpires on a country-by-country basis on the later of (1) the date the last remaining valid claim in the licensed patents expires, lapses or is invalidated in thatcountry, the product is not covered by data protection clauses, and the sales of a lawful generic version of the product account for more than a specified percentageof the total sales of all pharmaceutical products containing the licensed compound in that country; or (2) a period of 10 years after the first commercial sale of thelicensed products in such country, unless it is sooner terminated.10. Research Agreements Abaloparatide-SC Phase 3 Clinical Trial —On March 29, 2011, the Company and Nordic entered into a Clinical Trial Services Agreement (the "Clinical TrialServices Agreement"), a Work Statement NB-1, as amended on December 9, 2011, June 18, 2012, March 28, 2014, May 19, 2014, July 22, 2014, August 15, 2014and March 12, 2015 (the "Work Statement NB-1") and a Stock Issuance Agreement, as amended and restated on May 16, 2011, and as further amended onFebruary 21, 2013, March 28, 2014, and May 19, 2014 (the "Stock Issuance Agreement"). Pursuant to the Work Statement NB-1, Nordic managed the Phase 3clinical trial of abaloparatide-SC (the "Phase 3 Clinical Trial"). The Company recognized research and development expense for the amounts due to Nordic under the Work Statement NB-1 ratably over the estimated perpatient treatment period beginning upon enrollment in the Phase 3 Clinical Trial, or a twenty-month period. The Company recognized research and developmentexpense for the amounts due to Nordic under the fourth amendment to the Work Statement NB-1, which was recognized on a per patient basis when the end-of-study visit and all other required procedures were completed. The Company recorded no expense, $8.2 million, and $31.6 million during the years endedDecember 31, 2015, 2014, and 2013, respectively, for per patient costs incurred for patients that had enrolled in the Phase 3 Clinical Study. As of December 31,2015, all obligations due to Nordic under Work Statement NB-1 had been paid. Abaloparatide-SC Phase 3 Clinical Extension Study —On February 21, 2013, the Company entered into a Work Statement NB-3, as amended on February 28,2014, March 23, 2015, July 8, 2015 and October 21, 2015 (the "Work Statement NB-3"). Pursuant to the Work Statement NB-3, Nordic performed an extensionstudy to evaluate six months of standard-of-care osteoporosis management following the completion of the Phase 3 Clinical Trial (the "Extension Study"), and,upon completion of this initial six months, an additional period of 18 months of standard-of-care osteoporosis management (the "Second Extension"). In April 2015, the Company entered into an amendment to the Work Statement NB-3 (the "NB-3 Amendment"). The NB-3 Amendment was effective as ofMarch 23, 2015 and provides that Nordic will perform additional services, including additional monitoring of patients enrolled in the Second Extension. Paymentsin cash to be made to Nordic under the NB-3 Amendment are denominated in euros and total up to approximately €4.1 million ($4.5 million).110Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)10. Research Agreements (Continued) Payments in cash to be made to Nordic under the Work Statement NB-3 are denominated in both euros and U.S. dollars and total up to €11.9 million($12.9 million) and $1.1 million, respectively. In addition, payments are due to Nordic in connection with the Work Statement NB-3 pursuant to the Stock IssuanceAgreement, as discussed below. As of December 31, 2015, services related to the Second Extension are ongoing and all obligations due to Nordic in relation to theExtension Study have been paid. The Company recognizes research and development expense for the amounts due to Nordic under the Extension Study and the Second Extension ratably overthe estimated per patient treatment periods beginning upon enrollment, or over a nine-month and nineteen-month period, respectively. The Company recorded$5.4 million, $9.6 million, and $4.5 million for the years ended December 31, 2015, 2014, and 2013 respectively, for per patient costs incurred. As of December 31, 2015, the Company had a liability of $2.9 million reflected in accrued expenses and other current liabilities on the consolidated balancesheet resulting from services provided by Nordic under the Second Extension, which are payable in cash. Stock Issuance Agreement —Pursuant to the Stock Issuance Agreement, Nordic agreed to purchase 6,443 shares of the Company's Series A-5 convertiblepreferred stock, which provided Nordic with the right to receive quarterly stock dividends, payable in shares of the Company's Series A-6 convertible preferredstock ("Series A-6") for services rendered under Work Statement NB-1 and Work Statement NB-3. The Stock Issuance Agreement was later amended to providethat in the event an initial public offering of the Company's common stock occurred prior to June 30, 2014, any rights to receive stock dividends in relation to WorkStatement NB-1 and Work Statement NB-3, for all periods of time after 2014, would be changed from the right to receive stock to the right to receive a total cashpayment from the Company of $4.3 million, payable in ten equal monthly installments of $430,000 beginning on March 31, 2015. The amendment also stipulatedthat all consideration to be paid to Nordic pursuant to the Stock Issuance Agreement at any time after the consummation of an initial public offering be payable incash. As the Company completed an initial public offering on June 11, 2014, Nordic no longer has the right to receive stock from the Company and has been paidin cash for all periods after June 11, 2014. Prior to the issuance of shares of stock to Nordic in satisfaction of quarterly dividends earned under Work Statement NB-1 and Work Statement NB-3, theliability to issue shares of stock was being accounted for as a liability in the Company's balance sheet, based upon the fair value of the Series A-6. Changes in thefair value from the date of accrual to the date of issuance of the Series A-6 shares were recorded as a gain or loss in other (expense) income in the statement ofoperations.11. Stock-based Compensation The Company has the following stock-based compensation plans as of December 31, 2015, under which equity awards have been granted to employees,directors and consultants:•2003 Long-Term Incentive Plan; and •2011 Equity Incentive Plan. The 2011 Equity Incentive Plan replaced the 2003 Long-Term Incentive Plan when the board of directors approved the new plan on November 7, 2011. As ofDecember 31, 2015, an aggregate of111Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)11. Stock-based Compensation (Continued)approximately 6,160,000 shares have been authorized for issuance under the Company's stock-based compensation plans, with approximately 4,408,000 optionsoutstanding. The number of common shares available for granting of future awards under these plans was approximately 1,100,000 at December 31, 2015. 2003 Long-Term Incentive Plan —The Company's 2003 Long-Term Incentive Plan (the "Incentive Plan") provides for the granting of incentive stock optionsand nonqualified options to key employees, directors and consultants of the Company. The exercise price of the incentive stock options, as determined by the boardof directors, must be at least 100% (110% in the case of incentive stock options granted to a stockholder owning in excess of 10% of the Company's common stock)of the common stock fair value as of the date of the grant. The provisions of the Incentive Plan limit the exercise of incentive stock options, but in no case may theexercise period extend beyond ten years from the date of grant (five years in the case of incentive stock options granted to a stockholder owning in excess of 10%of the Company's common stock). Stock options generally vest over a four-year period. Certain options contain explicit performance conditions. The Companyauthorized approximately 884,000 shares of common stock for issuance under the Incentive Plan. 2011 Equity Incentive Plan —The Company's 2011 Equity Incentive Plan (the "Equity Plan") provides for the granting of incentive stock options andnonqualified options to key employees, directors and consultants of the Company. The exercise price of the incentive stock options, as determined by the board ofdirectors, must be at least 100% (110% in the case of incentive stock options granted to a stockholder owning in excess of 10% of the Company's common stock) ofthe common stock fair value as of the date of the grant. The provisions of the Equity Plan limit the exercise of incentive stock options, but in no case may theexercise period extend beyond ten years from the date of grant (five years in the case of incentive stock options granted to a stockholder owning in excess of 10%of the Company's common stock). Stock options generally vest over a four-year period. During 2015, the Company also issued stock options to certain members ofits board of directors which vested immediately. Certain options contain explicit performance conditions. The Company has authorized approximately 5,276,000shares of common stock for issuance under the Equity Plan. In addition, the shares remaining available for issuance under the Incentive Plan were assumed asshares authorized under the Equity Plan. Options —The Company has historically granted stock options at exercise prices no less than the fair value of its common stock as determined by its board ofdirectors, with input from management. Prior to the Company's initial public offering, the Company's board of directors has historically determined, with inputfrom management, the estimated fair value of the Company's common stock on the date of grant based on a number of objective and subjective factors, including:•the prices at which the Company sold shares of convertible preferred stock; •the superior rights and preferences of securities senior to the Company's common stock at the time of each grant; •the likelihood of achieving a liquidity event such as a public offering or sale of the Company; •the Company's historical operating and financial performance and the status of its research and product development efforts; and112Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)11. Stock-based Compensation (Continued)•achievement of enterprise milestones, including entering into collaboration and license agreements. Subsequent to the Company's initial public offering, exercise prices in the case of non-qualified and incentive stock options are not less than the fair value ofthe underlying common stock on the date of grant, as determined under the Equity Plan. The Company uses the Black-Scholes option-pricing model to estimate the grant date fair value of its employee stock options. The weighted-average grant-date fair value per share of options granted during 2015, 2014, and 2013 was $30.52, $8.26, and $4.67 respectively. The weighted-average assumptions used in theBlack-Scholes option-pricing model were as follows: A summary of stock option activity for the year ended December 31, 2015 is as follows (in thousands, except for per share and weighted-average contractuallife amounts): The aggregate intrinsic value of options exercised (i.e., the difference between the market price at exercise and the price paid by employees to exercise theoption) during the years ended December 31, 2015 and 2014 was $14.7 million and $0.7 million, respectively.113 Years Ended December 31, 2015 2014 2013 Expected term (years) 6.08 6.06 6.25 Volatility 55% 59% 62%Expected dividend yield 0% 0% 0%Risk-free interest rates 1.72% 2.06% 2.45% Shares Weighted-Average Exercise Price (in dollars per share) Weighted-Average Contractual Life (In Years) Aggregate Intrinsic Value Options outstanding at December 31, 2014 3,220 $13.58 Granted 1,487 57.75 Exercised (268) 8.73 Cancelled (31) 17.31 Expired — — Options outstanding at December 31, 2015 4,408 $28.75 8.24 $151,544 Options exercisable at December 31, 2015 1,738 $12.21 6.96 $85,747 Options vested or expected to vest at December 31, 2015 4,316 $28.43 8.22 $149,570 Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)11. Stock-based Compensation (Continued) The following table summarizes stock-based compensation expense by financial statement line (in thousands): Performance Units —In September 2015, the Company awarded 25,000 performance units ("PUs") to an employee. Each PU which is earned entitles theholder to receive one share of the Company's common stock if and when the PU vests. The PUs can be earned in the three years subsequent to the grant date if theCompany's average closing stock price over 45 consecutive trading days that begin and end during such three-year period reaches certain thresholds that were set atthe time of issuance. The vesting of any earned units is subject to the employee's continued employment one year from the last day of the measurement period forwhich the PUs are earned. Compensation expense is recognized over the derived service period, calculated using a Monte Carlo simulation analysis. The weighted-average grant-date fair value per unit of PUs granted during the year ended December 31, 2015 was $49.59, which was calculated using aMonte Carlo simulation analysis. This valuation methodology utilizes several key assumptions including the forecasted stock price, stock price volatility, risk-freerate as of valuation date, stock price as of grant date and the trigger for the performance condition to be met. As of December 31, 2015, there was approximately $51.3 million of total unrecognized compensation expense related to unvested share-based compensationarrangements, which is expected to be recognized over a weighted-average period of approximately 3 years.114 Years Ended December 31, 2015 2014 2013 Research and development $7,864 $1,953 $302 General and administrative 6,870 5,117 1,206 Share-based compensation expense included in operating expenses $14,734 $7,070 $1,508 Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)12. Net Loss Per Share Basic and diluted net loss per share is calculated as follows (in thousands, except share and per share amounts): The following potentially dilutive securities, prior to the use of the treasury stock method, have been excluded from the computation of diluted weighted-average shares outstanding, as they would be anti-dilutive. For the years ended December 31, 2015, 2014, and 2013 all of the Company's classes of convertiblepreferred stock, options to purchase common stock, warrants and performance units outstanding were assumed to be anti-dilutive as earnings attributable tocommon stockholders was in a loss position.13. Income Taxes As of December 31, 2015 the Company had federal and state net operating loss ("NOL") carryforwards of approximately $419.5 million and $323.0 million,respectively, which may be used to offset future taxable income. The Company also had federal and state tax credits of $5.8 million and $0.8 million, respectively,to offset future tax liabilities. The NOL and tax credit carryforwards will expire at various dates through 2035, and are subject to review and possible adjustment byfederal and state tax authorities. The Internal Revenue Code contains provision that may limit the NOL and tax credit carryforwards available to be used in anygiven year in the event of certain changes in the ownership interests of significant stockholders under Section 382 of the Internal Revenue Code.115 Year Ended December 31, 2015 2014 2013 Numerator: Net loss $(101,526)$(62,479)$(60,690)Accretion of preferred stock — (9,000) (17,471)Loss attributable to common stockholders—basic (101,526) (71,479) (78,161)Effect of dilutive convertible preferred stock — — — Loss attributable to common stockholders—diluted $(101,526)$(71,479)$(78,161)Denominator: Weighted-average number of common shares used in loss pershare—diluted 39,643,099 17,699,487 383,310 Loss per share—basic and diluted $(2.56)$(4.04)$(203.91) Year Ended December 31 2015 2014 2013 Convertible preferred stock — 3,857,664 6,617,686 Options to purchase common stock 3,903,051 2,466,492 1,743,890 Warrants 822,726 1,271,520 545,797 Performance units — — — Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)13. Income Taxes (Continued)Approximately $14.1 million of the federal and state NOL carryforwards are attributable to excess tax benefits which will be recorded as an increase to additionalpaid-in capital when realized. A reconciliation of income taxes computed using the U.S. federal statutory rate to that reflected in operations follows (in thousands): The Company is subject to Massachusetts net worth taxes, not based on income, which is largely offset by allowable tax credits and recorded as a componentof operating expenses. The principal components of the Company's deferred tax assets are as follows (in thousands): Effective December 31, 2015, the Company early adopted ASU 2015-17 on a prospective basis. ASU 2015-17 requires deferred tax liabilities and assets to beclassified as noncurrent in a classified116 Year Ended December 31, 2015 2014 2013 Income tax benefit using U.S. federal statutory rate $(34,391)$(21,243)$(20,635)State income taxes, net of federal benefit (4,434) (2,494) (2,255)Stock-based compensation 752 149 92 Research and development tax credits (1,469) (499) (1,277)Change in the valuation allowance 39,291 23,186 27,194 Permanent items 26 910 (3,085)Other 225 (9) (34) $— $— $— December 31, 2015 2014 Current assets: Accrued expenses $— $671 Gross current deferred tax assets — 671 Valuation allowance — (671)Net current deferred tax assets $— $— Non-current assets: Net operating loss carryforwards $154,239 $121,278 Capitalized research and development 263 356 Research and development credits 6,313 4,844 Depreciation and amortization (119) (47)Accrued Expenses 1,073 — Stock-based compensation 7,753 3,158 Other 29 — Gross non-current deferred tax assets 169,551 129,589 Valuation allowance (169,551) (129,589)Net non-current deferred tax assets $— $— Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)13. Income Taxes (Continued)statement of financial position, instead of separating deferred income tax liabilities and assets into current and noncurrent amounts. Adoption of this ASU resultedin a reclassification of our net current deferred tax asset to the net non-current deferred tax asset in our Consolidated Balance Sheet as of December 31, 2015. Noprior periods were retrospectively adjusted. The Company has recorded a valuation allowance against its deferred tax assets in each of the years ended December 31, 2015 and 2014, because theCompany's management believes that it is more likely than not that these assets will not be realized. The increase in the valuation allowance in 2015 primarilyrelates to the net loss incurred by the Company. As of December 31, 2015, the Company has no unrecognized tax benefits or related interest and penalties accrued. The Company has not, as yet, conducted astudy of research and development credit carryforwards. In addition, the Company is in the process of conducting an Internal Revenue Code Section 382 study,which may impact its ability to utilize available NOL and tax credit carryforwards. These studies may result in adjustments to the Company's research anddevelopment credit carryforwards and NOL carryforwards; however, until a study is completed and any adjustment is known, no amounts are being presented as anuncertain tax position. A full valuation allowance has been provided against the Company's research and development credits and net operating loss carryforwardand, 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 consolidatedbalance sheet or consolidated statement of operations if an adjustment were required. The Company would recognize both accrued interest and penalties related tounrecognized benefits in income tax expense. The Company has not recorded any interest or penalties on any unrecognized benefits since inception. The statute of limitations for assessment by the Internal Revenue Service ("IRS") and state tax authorities remains open for years 2012 through 2015. TheCompany files income tax returns in the United States, Colorado, Connecticut, Florida, Pennsylvania, New Jersey, New York, and Massachusetts. There arecurrently no federal or state audits in progress.14. Commitments and Contingencies Litigation —The Company may be subject to legal proceedings and claims which arise in the ordinary course of its business. In the Company's opinion, theultimate resolution of these matters is not expected to have a material effect on its consolidated financial statements. The Company records a liability in itsconsolidated financial statements for these matters when a loss is known or considered probable and the amount can be reasonably estimated. The Companyreviews these estimates each accounting period as additional information is known and adjusts the loss provision when appropriate. If a matter is both probable toresult in a liability and the amounts of loss can be reasonably estimated, the Company estimates and discloses the possible loss or range of loss to the extentnecessary to make the consolidated financial statements not misleading. If the loss is not probable or cannot be reasonably estimated, a liability is not recorded inits consolidated financial statements. Commitments —The Company leases certain office space in Massachusetts and New Jersey under non-cancellable operating leases that expire over variousterms through 2020.117Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)14. Commitments and Contingencies (Continued) The Company is obligated to make monthly rent payments pursuant to these non-cancellable agreements as set forth below (in thousands): Rent expense for the years ended December 31, 2015, 2014, and 2013 was $0.6 million, $0.2 million and $0.2 million, respectively.15. Related Party Transactions On July 24, 2013, the Company entered into a Consulting Agreement with Morana Jovan-Embiricos, Ph.D. (the "Consulting Agreement"), a member of theCompany's board of directors. Pursuant to the Consulting Agreement, Dr. Jovan-Embiricos agreed to provide financial and strategic consulting services as may berequested by the Company, and such other consulting services as may be reasonably requested by the Company, from time to time from July 1, 2013 until June 30,2014. The Company agreed to pay Dr. Jovan-Embiricos an aggregate consulting fee in cash of $160,000, of which $80,000 was paid on July 30, 2013 and theremaining $80,000 was paid on October 2, 2013. As of December 31, 2015, no amounts were due to or from Dr. Jovan-Embiricos. On January 23, 2014, the Company entered into a consulting agreement with Orbit Advisors Limited (the "Orbit Agreement"), a Swiss company ("Orbit"), andMorana Jovan-Embiricos, Ph.D. and an agreement terminating the Consulting Agreement dated July 24, 2013. The Orbit Agreement was effective as of January 22,2014 and would continue in effect until December 31, 2014 or until the earlier termination thereof in accordance with its terms (the "Term"). Pursuant to the OrbitAgreement, Orbit had agreed to provide financial and strategic consulting services as may be requested by the Company, and such other consulting services as mayhave been reasonably requested by the Company, from time to time during the Term. The Company agreed to pay Orbit an aggregate consulting fee in cash of$400,000 in four equal installments of $100,000 on each of January 31, 2014, June 30, 2014, September 30, 2014 and December 31, 2014. The Orbit Agreementcontained customary provisions, applicable to both Orbit and Dr. Jovan-Embiricos, as Orbit's representative under the Orbit Agreement, regarding the treatment ofthe Company's confidential information and assignment of inventions, as well as an obligation of Orbit and Dr. Jovan-Embiricos to not solicit, during the Term andfor a period of one year thereafter, any person or entity engaged by the Company as an employee, customer or supplier of, or consultant or advisor to, the Companyto terminate such party's relationship with the Company. On February 27, 2014, the Company entered into a letter agreement terminating the Orbit Agreement. Asof December 31, 2015, no amounts were due to or from Orbit Advisors Limited.118Years ended December 31, Future Lease Commitments 2016 $1,944 2017 2,214 2018 1,613 2019 1,327 2020 1,175 Total minimum lease payments $8,273 Table of ContentsRadius Health, Inc.Notes to Consolidated Financial Statements (Continued)16. Selected Quarterly Financial Data (Unaudited) Selected quarterly financial data for the years ended December 31, 2015 and 2014 is as follows (in thousands, except for share and per share data):119 Three Months Ended March 31, June 30, September 30, December 31, 2015: Net loss $(17,057) (22,965) (28,264)$(33,240)Net loss applicable to common stock (17,057) (22,965) (28,264) (33,240)Net loss per share—basic and diluted (0.47) (0.61) (0.68) (0.77)Weighted-average common shares outstanding—basic anddiluted 36,268,975 37,895,651 41,331,612 42,924,137 2014: Net loss $(14,488)$(12,609)$(17,420)$(17,962)Net loss applicable to common stock (19,457) (16,640) (17,420) (17,962)Net loss per share—basic and diluted (50.45) (2.22) (0.59) (0.55)Weighted-average common shares outstanding—basic anddiluted 385,664 7,500,148 29,746,426 32,678,459 Table of ContentsITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE. None.ITEM 9A. CONTROLS AND PROCEDURES. Limitations on Effectiveness of Controls and Procedures In designing and evaluating our disclosure controls and procedures and internal control over financial reporting, management recognizes that any controls andprocedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design ofdisclosure controls and procedures and internal control over financial reporting must reflect the fact that there are resource constraints and that management isrequired to apply judgment in evaluating the benefits of possible controls and procedures relative to their costs.Evaluation of Disclosure Controls and Procedures Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated as of the end of the period covered by thisAnnual Report on Form 10-K, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the SecuritiesExchange Act of 1934, as amended, or the Exchange Act. Based on that evaluation, our Chief Executive Officer and Chief Financial Officer concluded that ourdisclosure controls and procedures were effective at the reasonable assurance level as of December 31, 2015.Management's Annual Report on Internal Control Over Financial Reporting Our 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 management, with the participation of our Chief Executive Officer and Chief Financial Officer, assessed the effectiveness of ourinternal control over financial reporting as of December 31, 2015, based on the criteria set forth in Internal Control—Integrated Framework issued by theCommittee of Sponsoring Organizations of the Treadway Commission (2013 framework). Based on that assessment, our management concluded that our internalcontrol over financial reporting was effective as of December 31, 2015. The effectiveness of our internal control over financial reporting as of December 31, 2015 has been audited by Ernst & Young LLP, an independent registeredpublic accounting firm, as stated in their report which is contained in Item 9A of this Annual Report on Form 10-K.Changes in Internal Control Over Financial Reporting There was no change in our internal control over financial reporting during the quarter ended December 31, 2015 that has materially affected, or is reasonablylikely to materially affect, our internal control over financial reporting.120Table of ContentsReport of Independent Registered Public Accounting Firm The Board of Directors and Shareholders of Radius Health, Inc. We have audited Radius Health, Inc.'s internal control over financial reporting as of December 31, 2015, based on criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) (the COSO criteria). RadiusHealth, Inc.'s management is responsible for maintaining effective internal control over financial reporting, and for its assessment of the effectiveness of internalcontrol over financial reporting included in the accompanying Management's Annual Report on Internal Control over Financial Reporting. Our responsibility is toexpress an opinion on the company's internal control over financial reporting based on our audit. We conducted our audit in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standards require that weplan and perform the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects.Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, testing and evaluatingthe design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in thecircumstances. We believe that our audit provides a reasonable basis for our opinion. A company's internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting andthe preparation of consolidated financial statements for external purposes in accordance with generally accepted accounting principles. A company's internalcontrol over financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairlyreflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permitpreparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being madeonly in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detectionof unauthorized acquisition, use, or disposition of the company's assets that could have a material effect on the financial statements. Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation ofeffectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance withthe policies or procedures may deteriorate. In our opinion, Radius Health, Inc. maintained, in all material respects, effective internal control over financial reporting as of December 31, 2015, based onthe COSO criteria. We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States), the consolidated balance sheetsof Radius Health, Inc. as of December 31, 2015 and 2014, and the related consolidated statements of operations and comprehensive loss, convertible preferredstock, redeemable convertible preferred stock and stockholders' equity (deficit) and cash flows for each of the three years in the period ended December 31, 2015 ofRadius Health, Inc. and our report dated February 25, 2016 expressed an unqualified opinion thereon.Boston, Massachusetts February 25, 2016121 /s/ Ernst & Young LLPTable of ContentsITEM 9B. OTHER INFORMATION. None.122Table of ContentsPART III ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE. The following table sets forth the name, age and position of each of our executive officers and directors: Robert E. Ward has served as our President and Chief Executive Officer and as a member of our Board of Directors since December 2013. Prior to joiningRadius, Mr. Ward was Vice President for Strategy and External Alliances for the New Opportunities iMed of AstraZeneca, a biopharmaceutical company, from2011 to 2013. In addition, he served as Co-Chair of the Joint Development Committees in Astra Zeneca's drug development partnerships with Alcon and Galderma.Prior to AstraZeneca, from 2010 to 2011, Mr. Ward was the Managing Director of Harriman Biopartners, LLC, a biopharmaceutical company, and from 2006 to2010 he was the Vice President of Corporate Development for NPS Pharmaceuticals, a pharmaceutical company. Mr. Ward received a B.A. in Biology and a B.S.in Physiological Psychology, both from the University of California, Santa Barbara; an M.S. in Management from the New Jersey Institute of Technology; and anM.A. in Immunology from The Johns Hopkins University School of Medicine. We believe Mr. Ward is qualified to serve as a member of our Board of Directorsbecause of his role with us and his extensive operational knowledge of, and executive level management experience in, the global biopharmaceutical industry. Lorraine Fitzpatrick, M.D., has served as our Chief Medical Officer since July 2015. Prior to joining Radius, Dr. Fitzpatrick was a Medicine DevelopmentLeader and Group Director at GlaxoSmithKline, a pharmaceutical company, from August 2006 to July 2015. Prior to GlaxoSmithKline, she was an ExecutiveDirector at Amgen Inc., a biopharmaceutical company, focusing123Name PositionRobert E. Ward 58 President, Chief Executive Officer and DirectorLorraine Fitzpatrick, M.D. 61 Chief Medical OfficerB. Nicholas Harvey 55 Senior Vice President, Chief Financial Officer, Treasurerand SecretaryGary Hattersley, Ph.D. 49 Senior Vice President, Chief Scientific OfficerBrent Hatzis-Schoch. 51 Senior Vice President, General CounselDinesh Purandare 52 Senior Vice President, Head of Global OncologyDavid Snow 54 Chief Commercial OfficerGregory Williams, Ph.D. 56 Chief Development OfficerAlan H. Auerbach(3)(4) 46 DirectorWillard H. Dere, M.D(1)(2). 62 DirectorCatherine Friedman(1)(3) 55 DirectorAnsbert K. Gadicke, M.D.(2)(3) 57 DirectorJean-Pierre Garnier(3) 68 DirectorKurt C. Graves(2)(3)(4) 48 Chairman of the BoardOwen Hughes(1) 41 DirectorAnthony Rosenberg(4) 62 DirectorDebasish Roychowdhury(2) 54 Director(1)Member of the audit committee. (2)Member of the nominating and corporate governance committee. (3)Member of the compensation committee. (4)Member of the strategy committee.Table of Contentson osteoporosis and oncology from 2004 to 2006. She has served as Chair of the General Clinical Research Center study section of the National Center forResearch Resources, National Institute of Health, or NIH; on the Advocacy Committee of the American Society of Bone and Mineral Research, or ASBMR; and asChair of the Public Communications Committee and the Media Relations Steering Committee of The Endocrine Society, TES. She has also been a member of thePublications Committee of the ASBMR and TES and on the Advisory Committee for the Office of Research on Women's Health at the NIH. Dr. Fitzpatrick hasserved on the National Committee for Quality Assurance Technical Subgroup on Osteoporosis, the Clinical Guidelines Committee of TES, the Scientific ProgramCommittees of North American Menopause Society and the ASBMR, and as Associate Editor for The Mayo Clinic Proceedings and the American MedicalAssociation Scientific Advisory Board: Osteoporosis Guidelines. Dr. Fitzpatrick received a B.S. in Molecular Biology from Wellesley College and received hermedical degree from the Pritzker School of Medicine at the University of Chicago. B. Nicholas Harvey has served as our Senior Vice President, Chief Financial Officer, Treasurer and Secretary since November 2010, and served as a memberof our Board of Directors from November 2010 until the consummation of the merger of our predecessor company with us in May 2011, or the Merger. Prior tothat, Mr. Harvey served as the Chief Financial Officer and Senior Vice President of our predecessor company from December 2006 until the Merger. Mr. Harveyreceived a Bachelor of Economics degree and a Bachelor of Laws degree with first-class honors from the Australian National University and an M.B.A. from theHarvard Business School. Gary Hattersley, Ph.D., served as Chief Scientific Officer since January 2014. Prior to his current role, Dr. Hattersly served as our Senior Vice President ofPreclinical Development from December 2011 to December 2013, and President of Biology from May 2011 to December 2011. From 2003 until the Merger,Dr. Hattersly served in various roles in our predecessor company, including as Vice President of Biology, Senior Director of Research and Director of DiseaseBiology & Pharmacology. Dr. Hattersley received a Ph.D. in Experimental Pathology from St. George's Hospital Medical School. Brent Hatzis-Schoch has served as our Senior Vice President, General Counsel, since April 2015. Prior to joining Radius, from July 2013 to April 2015.Mr. Hatzis-Schoch was Senior Vice President and Chief Legal Counsel of Merz Pharma in Frankfurt, Germany. Prior to Merz, Mr. Hatzis-Schoch served for fiveyears as General Counsel to Agennix AG, a publicly-traded development stage biopharmaceutical company. He has held senior legal positions in the U.S. andinternationally, including as European legal counsel for Baxter International, Associate General Counsel of Pharmacia Corporation, and General Counsel of GPCBiotech AG. Mr. Hatzis-Schoch holds a J.D. from George Washington University and a B.A. from the University of Delaware. Dinesh Purandare has served as our Senior Vice President, Head of Global Oncology since March 2015. Prior to joining Radius, Mr. Purandare spent fiveyears at Sanofi Oncology, a pharmaceutical company. He held the role of Vice President and Head of Marketing from March 2010 to September 2012, and VicePresident and Project Head, from October 2012 to March 2015. He also co-chaired the Joint Development Committee (Oncology) of Sanofi and RegeneronPharmaceuticals and was a member of the Oncology Management Team at Sanofi. Prior to Sanofi, he served as Vice President and Head of Oncology Center ofExcellence at GlaxoSmithKline headquarters in the UK and held other senior positions at Pharmacia /Pfizer and Farmitalia Carlo Erba (Milan, Italy). Mr. Purandarereceived degrees in Business Management and Organic Chemistry from the University of Bombay. He also received a Diploma in Advanced MarketingManagement from the Chartered Institute of Marketing, U.K. David Snow has served as our Chief Commercial Officer since September 2015. Prior to joining Radius, Mr. Snow was President of the biopharmaceuticalcompany, AstraZeneca's China business from January 2012 to December 2014. He was also the first global commercialization Vice President for124Table of ContentsAstraZeneca's prescription medication Brilinta and head of U.S. Commercial Operations from March 2010 to December 2011. Before joining AstraZeneca,Mr. Snow held numerous global and US commercial leadership roles for Bristol-Myers Squibb, Searle and Hoechst-Roussel. He served on the Research andDevelopment based Pharmaceutical Association Committee industry association board in China for several years. Mr. Snow received his B.S. in BusinessAdministration from Auburn University, and an M.B.A from New York University—Leonard N. Stern School of Business. Gregory Williams, Ph.D., has served as our Chief Development Officer since January 2014. Prior to joining Radius, Dr. Williams was Vice President ofRegulatory Affairs, Global Product and Clinical Development, and Program Management with The Medicines Company, a biopharmaceutical company, from 2006to 2013. He was Vice President of Regulatory Affairs, Regulatory Compliance and Program Management for NPS Pharmaceuticals, a pharmaceutical company,from 2004 to 2006. Dr. Williams has a Ph.D. in Biopharmaceutics from Rutgers University and an M.B.A. from Cornell University. Alan H. Auerbach has served on our Board of Directors since May 2011 and served as a member of the Board of Directors our predecessor company fromOctober 2010 until the Merger. Mr. Auerbach is currently the Founder, Chief Executive Officer, President and Chairman of the Board of Puma Biotechnology, Inc.,a company dedicated to in-licensing and developing drugs for the treatment of cancer and founded in 2010. Previously, Mr. Auerbach founded CougarBiotechnology, or Cougar, in May 2003 and served as the company's Chief Executive Officer, President and as a member of its Board of Directors until July 2009.From July 2009 until January 2010, Mr. Auerbach served as the Co-Chairman of the Integration Steering Committee at Cougar after its acquisition by Johnson &Johnson. Mr. Auerbach received a B.S. in Biomedical Engineering from Boston University and an M.S. in Biomedical Engineering from the University of SouthernCalifornia. We believe Mr. Auerbach is qualified to serve as a member of our Board of Directors because of his business and professional experience, including hisleadership of Cougar in drug development, private and public financings and a successful sale of the business. Willard H. Dere, M.D. has served on our Board of Directors since November 2014. Dr. Dere has been Executive Director of Personalized Health at theUniversity of Utah Health Sciences Center, and a Professor of Medicine in the School of Medicine since November 2014. Prior to that, he served at Amgen Inc., abiopharmaceutical company, as the Senior Vice President, Global Development from December 2004 to June 2007, and from April 2014 to October 2014, and asInternational Chief Medical Officer from January 2007 to April 2014. Before he joined Amgen in 2003, Dr. Dere served as Vice President of Endocrine, Bone andGeneral Medicine Research and Development at Eli Lilly and Company, a biopharmaceutical company, where he also held various other roles in clinicalpharmacology, regulatory affairs, and both early-stage translational, and late-stage clinical research. Dr. Dere received B.A. degrees in history and zoology and aM.D. degree from the University of California, Davis. We believe Mr. Dere is qualified to serve as a member of our Board of Directors because of his strongmedical background and extensive experience in the pharmaceutical industry. Jean-Pierre Garnier has served on our Board of Directors since December 2015. Mr. Garnier is currently Chairman of the Board of Actelion Ltd., and waspreviously Chief Executive Officer of GlaxoSmithKline plc from 2000 to 2008. In addition, Mr. Garnier is also a member of the Board of Directors of UnitedTechnologies Corporation and of Renault S.A., and an Operating Partner at Advent International, a global private equity firm. Mr. Garnier previously served asChief Executive Officer of Pierre Fabre S.A. from 2008 to 2010, as Chief Executive Officer and Executive Member of the Board of Directors ofGlaxoSmithKline plc from 2000 to 2008 and as Chief Executive Officer of SmithKline Beecham plc in 2000 and as Chief Operating Officer and ExecutiveMember of the Board of Directors of SmithKline Beecham plc from 1996 to 2000. Mr. Garnier was previously Chairman of Cerenis from 2010 to 2011, and aboard member of the Stanford Advisory Council on Interdisciplinary Biosciences, Weill Cornell Medical College and the Dubai International Capital AdvisoryBoard. He is also a member of the Advisory Board of the Newman's Own Foundation. We believe Dr. Garnier is125Table of Contentsqualified to serve as a member of our Board of Directors because of his significant business and professional experience, including his extensive experience in thelife sciences industry, membership on various boards of directors and his previous leadership and management roles. Catherine Friedman has served on our Board of Directors since August 2015. Previously, Ms. Friedman held the position of Managing Director at MorganStanley from 1997 to 2006 and head of West Coast Healthcare and co-head of the Biotechnology Practice at Morgan Stanley from 1993 to 2006. Since 2007,Ms. Friedman has been a director of XenoPort Inc., where she serves on the Audit and Nominating and Governance Committees, and Enteromedics, where sheserves as Chair of the Audit Committee; in June 2014, she joined the Board of Innoviva (formerly known as Theravance), where she serves on the Audit andCompensation Committees; and in May 2013 she joined the Board of GSV Capital, a publicly traded investment fund, where she serves as Chair of the AuditCommittee and on the Valuation Committee. Ms. Friedman is a member of the Board of Trustees for Sacred Heart Schools in Atherton. She is a graduate ofHarvard University and received an MBA from the University of Virginia Darden School of Business, where she is currently a Darden School Foundation Board ofTrustees member. We believe Ms. Friedman is qualified to serve as a member of our Board of Directors due to her extensive experience as a member on variousboards of directors, her educational background and her previous leadership and management roles. Ansbert K. Gadicke, M.D. has served on our Board of Directors since May 2011 and served as a member of the board of directors of our predecessorcompany from November 2003 until the Merger. Dr. Gadicke has been the Co-Founder and Managing Director of MPM Capital, a venture capital firm, sinceAugust 1996. Dr. Gadicke received an M.D. from J.W. Goethe University in Frankfurt. Dr. Gadicke is a director of Chiasma, Inc., OSS Healthcare, Inc., SiderisPharmaceuticals, Inc., RWHD, Inc. and Mitokyne, Inc. He served on the board of directors of Idenix Pharmaceuticals, Inc. from 1998 to 2005, BioMarinPharmaceuticals, Inc. from 1997 to 2001, Verastem, Inc. from 2010 to 2012, Pharmasset, Inc. from 1999 to 2007 and PharmAthene, Inc. from 2004 to 2007. Webelieve Dr. Gadicke is qualified to serve as a member of our Board of Directors because of his business and professional experience, including his experience in theventure capital industry and his years of analyzing development opportunities in the life sciences sector. Kurt C. Graves has served on our Board of Directors since May 2011 and as Chairman of our Board of Directors since November 2011. Mr. Graves hasbeen the Chairman, President and Chief Executive Officer of Intarcia Therapeutics, a biotechnology company, since April 2012. Mr. Graves served as ExecutiveChairman of Biolex Therapeutics, a biotechnology company, from November 2010 to March 2012, and served as Executive Chairman of Intarcia Therapeuticsfrom August 2010 to April 2012. Previously, he served as Executive Vice President, Chief Commercial Officer and Head of Strategic Development at VertexPharmaceuticals Inc. from July 2007 to October 2009. Prior to joining Vertex, Mr. Graves held various leadership positions at Novartis pharmaceuticals from 1999to June 2007. He was also the first Chief Marketing Officer for the Pharmaceuticals division from September 2003 to June 2007. He currently serves as a directorof Intarcia Therapeutics, Pulmatrix Therapeutics and Achillion Pharmaceuticals. He served on the board of directors of Biolex Therapeutics and SpringleafTherapeutics from 2010 to 2012. Mr. Graves received a B.S. in Biology from Hillsdale College. We believe Mr. Graves is qualified to serve as a member of ourBoard of Directors because of his extensive experience in the life sciences industry, membership on various boards of directors and his leadership and managementexperience. Owen Hughes has served on our Board of Directors since April 2013. He has served as the Chief Business Officer and Head of Corporate Development atIntarcia Therapeutics, Inc., a biotechnology company, since February 2013. Prior to Intarcia, he served as a Director at Brookside Capital, a hedge fund under theBain Capital umbrella, managing public and private healthcare investments from March 2008 to January 2013. Mr. Hughes has served as a Senior PortfolioManager at Pyramis Global Advisors from 2006 to 2008, co-founder and partner at Triathlon Fund Management from 2003 to 2006,126Table of Contentsan Investment Associate at Ziff Brothers Investments from 2001 to 2003, and an Assistant Vice President at Morgan Stanley/Merrill Lynch from 1998 to 2001.Mr. Hughes is a director of Malin PLC. He earned a bachelor of arts from Dartmouth College. We believe Mr. Hughes is qualified to serve as a member of ourBoard of Directors because of his extensive business and professional experience, including his experience in the venture capital industry and years of analyzingdevelopment opportunities in the life sciences sector. Anthony Rosenberg has served on our Board of Directors since March 2015. From January 2013 to February 2015, Mr. Rosenberg served as Corporate Headof M&A and Licensing at Novartis International, a pharmaceutical company. From March 2005 to December 2012, he served as Global Head of BusinessDevelopment and Licensing at Novartis Pharmaceuticals. Prior to that, Mr. Rosenberg was Global Head of the Transplant and Immunology Business Unit atNovartis Pharmaceuticals from 2000 to 2005. Mr. Rosenberg initially joined Sandoz, a predecessor to Novartis, in 1980. Mr. Rosenberg served as a director ofIdenix Pharmaceuticals, Inc. from June 2009 to March 2012 and from December 2012 to March 2013. Mr. Rosenberg holds a B.Sc from the University of Leicesterand an M.Sc in physiology from the University of London. We believe Mr. Rosenberg is qualified to serve as a member of our Board of Directors due to hisextensive experience in mergers and acquisitions and licensing in the pharmaceutical sector. Debasish Roychowdhury has served on our Board of Directors since July 2015. Dr. Roychowdhury has been President of Nirvan Consultants, LLC sinceDecember 2013, where he advises biotechnology companies and institutions. He was one of the founding members of Seragon Pharmaceutical's Clinical andScientific Advisory Board and was Seragon's Chief Medical Officer, prior to its acquisition by Roche Pharma, from March 2014 to August 2014. Prior to Seragon,Dr. Roychowdhury was the Senior Vice President and Head of the Global Oncology Division at Sanofi from August 2009 to November 2013. Prior to that, heserved as the Vice President for Clinical Development at GlaxoSmithKline, from 2005 to 2009, and directed the Oncology Global Regulatory group at Eli Lilly andCompany, a pharmaceutical company, from 1999 to 2005. Prior to his role in industry, Dr. Roychowdhury served as faculty member at the University ofCincinnati. He received his M.D from the All India Institute of Medical Sciences. He is a member of the Board of Directors for Celvad S.A. and Lytix BiopharmaAS. We believe Dr. Roychowdury is qualified to serve as a member of our Board of Directors because of his strong medical background, specifically related tooncology, and extensive experience in the pharmaceutical industry.Code of Business Conduct and Ethics We have adopted a code of business conduct and ethics that applies to all of our employees, officers and directors, including those officers responsible forfinancial reporting. The code of business conduct and ethics is available on our website at www.radiuspharm.com. Any amendments to the code, or any waivers ofits requirements, will be disclosed on our website. Information contained on or accessible through our website is not incorporated by reference into this report, andyou should not consider information contained on or accessible through our website to be part of this report. The remainder of the response to this item is contained in our definitive Proxy Statement for our 2016 Annual Meeting of Stockholders and is incorporatedherein by reference.ITEM 11. EXECUTIVE COMPENSATION. The information required to be disclosed by this item is contained in our definitive Proxy Statement for our 2016 Annual Meeting of Stockholders and isincorporated herein by reference.127Table of ContentsITEM 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS. The information required to be disclosed by this item is contained in our definitive Proxy Statement for our 2016 Annual Meeting of Stockholders and isincorporated herein by reference.ITEM 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE. The information required to be disclosed by this item is contained in our definitive Proxy Statement for our 2016 Annual Meeting of Stockholders and isincorporated herein by reference.ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES. The information required to be disclosed by this item is contained in our definitive Proxy Statement for our 2016 Annual Meeting of Stockholders and isincorporated herein by reference.128Table of ContentsPART IV ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES. (a)Financial Statements The following consolidated financial statements and supplementary data are included in Part II of Item 8 filed of this Annual Report on Form 10-K:(b)Financial Statement Schedules All financial statement schedules have been omitted because they are not applicable or are not required, or because the information required to be set forththerein is included in the consolidated financial statements or notes thereto.(c)Exhibits The Exhibit Index follows the signature pages hereof and is incorporated herein by reference.129Report of Independent Registered Public Accounting Firm 90 Consolidated Balance Sheets as of December 31, 2015 and 2014 91 Consolidated Statements of Operations and Comprehensive Loss for the years ended December 31, 2015, 2014 and 2013 92 Consolidated Statements of Convertible Preferred Stock, Redeemable Convertible Preferred Stock and Stockholders'Equity (Deficit) for the years ended December 31, 2015, 2014 and 2013 93 Consolidated Statements of Cash Flows for the years ended December 31, 2015, 2014 and 2013 95 Notes to Consolidated Financial Statements 96 Table of ContentsSIGNATURES Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this annual report to be signed on itsbehalf by the undersigned, thereunto duly authorized.Date: February 25, 2016 Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed by the following persons on behalf of the registrant and in thecapacities and on the dates indicated.130 RADIUS HEALTH, INC. By: /s/ ROBERT E. WARD Robert E. Ward President and Chief Executive OfficerSignature Title Date /s/ ROBERT E. WARD Robert E. Ward Chief Executive Officer and Director (PrincipalExecutive Officer) February 25, 2016/s/ B. NICHOLAS HARVEY B. Nicholas Harvey Chief Financial Officer (Principal Accountingand Financial Officer) February 25, 2016/s/ ALAN H. AUERBACH Alan H. Auerbach Director February 25, 2016/s/ WILLARD H. DERE Willard H. Dere Director February 25, 2016/s/ CATHERINE FRIEDMAN Catherine Friedman Director February 25, 2016/s/ ANSBERT K. GADICKE Ansbert K. Gadicke Director February 25, 2016/s/ JEAN-PIERRE GARNIER Jean-Pierre Garnier Director February 25, 2016Table of Contents131Signature Title Date /s/ KURT C. GRAVES Kurt C. Graves Director February 25, 2016/s/ OWEN HUGHES Owen Hughes Director February 25, 2016/s/ ANTHONY ROSENBERG Anthony Rosenberg Director February 25, 2016/s/ DEBASISH ROYCHOWDHURY Debasish Roychowdhury Director February 25, 2016Table of ContentsEXHIBIT INDEX 132Exhibit Number Exhibit Description Form File No. Exhibit Filing Date Filed/ Furnished Herewith 3.1 Restated Certificate of Incorporation, filed on June 11,2014 8-K 001-35726 3.1 6/13/14 3.2 Amended and Restated By-Laws 8-K 001-35726 3.2 6/13/14 4.1 Fifth Amended and Restated Stockholders' Agreement,dated April 24, 2014, by and among the Company andthe stockholders party thereto S-1/A 333-194150 4.2 4/25/14 10.1 Form of Warrant to Purchase Shares of Common Stockin connection with the Series B Convertible PreferredStock and Warrant Purchase Agreement, issued by theCompany to certain investors and attached schedule withdetails 8-K 001-35726 10.2 4/25/13 10.2 Form of Warrant to Purchase Shares of Common Stockin connection with the Series B-2 Convertible PreferredStock and Warrant Purchase Agreement, issued by theCompany to certain investors and attached schedule withdetails 8-K 001-35726 10.2 2/21/14 10.3 Form of Warrant to Purchase Shares of Series A-1Convertible Preferred Stock issued by the Company toGE Capital Equity Investments 10-K 001-35726 10.5 3/10/15 10.4^Clinical Trial Services Agreement, dated March 29,2011, by and between the Company, as successor toRadius Health, Inc., and Nordic BioScience ClinicalDevelopment VII A/S 8-K/A 000-53173 10.1 10/24/11 Table of Contents133Exhibit Number Exhibit Description Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10.5^Work Statement NB-1, dated March 29, 2011, by andbetween the Company and Nordic Bioscience ClinicalDevelopment VII A/S, as amended on December 9,2011, June 18, 2012, November 6, 2013, March 28,2014, May 19, 2014 and July 22, 2014 10-K 001-35726 10.11 3/10/15 10.5(a)Amendment No. 8 to Work Statement NB-1, effective asof August 15, 2014, by and between the Company andNordic Bioscience Clinical Development VII A/S * 10.5(b)Amendment No. 9 to Work Statement NB-1, effective asof March 12, 2015, by and between the Company andNordic Bioscience Clinical Development VII A/S 10-Q 001-35726 10.4 5/6/15 10.6^Work Statement NB-2, dated February 21, 2013, by andbetween the Company and Nordic Bioscience ClinicalDevelopment VII A/S, as amended on November 6,2013 10-K 001-35726 10.12 3/10/15 10.7^Work Statement NB-3, dated February 21, 2013, by andbetween the Company and Nordic Bioscience ClinicalDevelopment VII A/S, as amended on February 28, 2014 10-K 001-35726 10.13 3/10/15 10.7(a)Amendment No. 2 to Work Statement NB-3, effective asof March 23, 2015, by and between the Company andNordic Bioscience Clinical Development VII A/S 10-Q 001-35726 10.5 5/6/15 10.7(b)Amendment No. 3 to Work Statement NB-1, effective asof July 8, 2015, by and between the Company andNordic Bioscience Clinical Development VII A/S 10-Q 001-35726 10.8 8/6/15 Table of Contents134Exhibit Number Exhibit Description Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10.7(c)Amendment No. 4 to Work Statement NB-3, effective asof October 21, 2015, by and between the Company andNordic Bioscience Clinical Development VII A/S * 10.7(d)Amendment No. 5 to Work Statement NB-3, effective asof January 15, 2016, by and between the Company andNordic Bioscience Clinical Development VII A/S * 10.8 Amended and Restated Stock Issuance Agreement, datedMay 16, 2011, by and between the Company, assuccessor to Radius Health, Inc., and Nordic BioScienceClinical Development VII A/S, as amended onFebruary 21, 2013, March 28, 2014 and May 19, 2014 10-K 001-35726 10.14 3/10/15 10.9^License Agreement, dated September 27, 2005, by andbetween the Company, as successor to Nuvios, Inc., andIpsen Pharma SAS (f/k/a SCRAS S.A.S.) on behalf ofitself and its affiliates, as amended on September 12,2007 and May 11, 2011 10-K 001-35726 10.15 3/10/15 10.10^Pharmaceutical Development Agreement, datedJanuary 2, 2006, by and between the Company, assuccessor to Radius Health, Inc., and Beaufour IpsenIndustrie SAS, as amended on January 1, 2007,January 1, 2009, June 16, 2010 and December 15, 2011 10-K 001-35726 10.16 3/10/15 10.10(a)Amendment No. 6, dated August 14, 2015, to thePharmaceutical Development Agreement, datedJanuary 2, 2006, by and between the Company andBeaufour Ipsen Industrie SAS, as amended 10-Q 001-35726 10.4 11/5/15 Table of Contents135Exhibit Number Exhibit Description Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10.11^Development and Manufacturing Services Agreement,dated October 16, 2007, by and between the Company,as successor to Radius Health, Inc., and LONZASales Ltd., as amended on May 19, 2011 and January 30,2014, and Work Orders thereunder through March 9,2014 10-K 001-35726 10.17 3/10/15 10.11(a)Amendment No. 3 to Development and ManufacturingServices Agreement, dated December 31, 2015, by andbetween the Company and LONZA Sales Ltd. * 10.11(b)Work Order #7, dated February 24, 2015, to theDevelopment and Manufacturing Agreement, datedOctober 16, 2007, by and between the Company, assuccessor to Radius Health, Inc., and LONZA Sales Ltd. 10-Q 001-35726 10.7 5/6/15 10.11(c)^Work Order #8, dated March 27, 2015, to theDevelopment and Manufacturing Services Agreement,dated October 16, 2007, by and between the Company,as successor to Radius Health, Inc., and LONZASales Ltd., as amended 10-Q 001-35726 10.4 8/6/15 10.11(d)^Work Order #9, dated May 7, 2015, to the Developmentand Manufacturing Services Agreement, datedOctober 16, 2007, by and between the Company, assuccessor to Radius Health, Inc., and LONZA Sales Ltd.,as amended 10-Q 001-35726 10.5 8/6/15 10.11(e)^Work Order #10, dated May 22, 2015, to theDevelopment and Manufacturing Services Agreement,dated October 16, 2007, by and between the Company,as successor to Radius Health, Inc., and LONZASales Ltd., as amended 10-Q 001-35726 10.6 8/6/15 Table of Contents136Exhibit Number Exhibit Description Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10.11(f)^Work Order No. 11, dated August 11, 2015, to theDevelopment and Manufacturing Services Agreement,dated October 16, 2007, by and between the Companyand LONZA Sales Ltd., as amended 10-Q 001-35726 10.2 11/5/15 10.11(g)^Work Order No. 12, dated August 24, 2015, to theDevelopment and Manufacturing Services Agreement,dated October 16, 2007, by and between the Companyand LONZA Sales Ltd., as amended 10-Q 001-35726 10.3 11/5/15 10.11(h)^Work Order No.13, dated September 28, 2015, to theDevelopment and Manufacturing Services Agreement,dated October 16, 2007, by and between the Companyand LONZA Sales Ltd., as amended 10-Q 001-35726 10.7 11/5/15 10.12^Development and Clinical Supplies Agreement, datedJune 19, 2009, by and among the Company, as successorto Radius Health, Inc., and 3M Co. and 3M InnovativeProperties Co., as amended on December 31, 2009,September 16, 2010, September 29, 2010, March 2,2011 and November 30, 2012 and Change Order Formsthereunder through March 9, 2014 10-K 001-35726 10.18 3/10/15 10.12(a)Change Order Form #22, dated March 2, 2015, to theDevelopment and Clinical Supplies Agreement, datedJune 19, 2009, by and among the Company and 3M Co.and 3M Innovative Properties Co., as amended 10-Q 001-35726 10.6 5/6/15 Table of Contents137Exhibit Number Exhibit Description Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10.12(b)^Change Order Form #23, dated August 26, 2015, to FifthAmendment to Development and Clinical SuppliesAgreement, effective as of November 30, 2012, by andamong the Company and 3M Co. and 3M InnovativeProperties Co. 10-Q 001-35726 10.5 11/5/15 10.12(b)^Change Order Form #26, dated May 13, 2015, to FifthAmendment to Development and Clinical SuppliesAgreement, effective as of November 30, 2012, by andamong the Company and 3M Co. and 3M InnovativeProperties Co. 10-Q 001-35726 10.3 8/6/15 10.13^License Agreement, dated June 29, 2006, by andbetween the Company and Eisai Co., Ltd. 8-K/A 000-53173 10.25 10/24/11 10.13(a)^License Agreement Amendment No. 1, dated March 9,2015, by and between the Company and Eisai Co. Ltd. 10-Q 001-35726 10.3 5/6/15 10.14†Radius Health, Inc. 2003 Long-Term Incentive Plan (asamended) 10-K 001-35726 10.20 3/10/15 10.15†Radius Health, Inc. 2003 Long-Term Incentive PlanForm of Stock Option Agreement 8-K 000-53173 10.32 5/23/11 10.16†Radius Health, Inc. 2011 Equity Incentive Plan (asamended and restated) 8-K 001-35726 10.1 5/11/15 10.17†Form of Radius Health, Inc. 2011 Equity Incentive PlanStock Option Agreement S-1/A 333-175091 10.83 11/7/11 10.18†Radius Health, Inc. Non-Employee DirectorCompensation Program 10-K 001-35726 10.24 3/10/15 10.19†Employment Letter Agreement, dated November 14,2003, by and between the Company, as successor toNuvios, Inc., and Gary Hattersley 8-K 000-53173 10.49 5/23/11 Table of Contents138Exhibit Number Exhibit Description Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10.20†Employment Letter Agreement, dated November 15,2006, by and between the Company, as successor toRadius Health, Inc., and B. Nicholas Harvey 8-K 000-53173 10.51 5/23/11 10.21†Executive Employment Agreement, dated as ofDecember 12, 2013, by and between the Company andRobert Ward 8-K 001-35726 10.1 12/17/13 10.22†Employment Letter Agreement, dated January 3, 2014,by and between the Company and Greg Williams S-1/A 333-194150 10.141 4/3/14 10.23†Form of Indemnification Agreement by and between theCompany and the individuals listed on Schedule Athereto 10-K 001-35716 10.30 3/10/15 10.24 Indenture of Lease, dated May 14, 2014, by and betweenthe Company and BP Bay Colony LLC 8-K 001-35726 10.1 5/20/14 10.24(a)First Amendment, dated September 9, 2015, to Lease,dated May 14, 2014, by and between the Company andBP Bay Colony LLC 10-Q 001-35726 10.6 11/5/15 21.1 Subsidiary of the Company * 23.1 Consent of Ernst & Young LLP, Independent RegisteredPublic Accounting Firm * 31.1 Rule 13a-14(a)/15d-14(a) Certification of ChiefExecutive Officer * 31.2 Rule 13a-14(a)/15d-14(a) Certification of ChiefFinancial Officer * 32.1 Section 1350 Certification of Chief Executive Officer ** 32.2 Section 1350 Certification of Chief Financial Officer ** 101.INS XBRL Instance Document * 101.SCH XBRL Taxonomy Extension Schema Document *Table of Contents139Exhibit Number Exhibit Description Form File No. Exhibit Filing Date Filed/ Furnished Herewith 101.CAL XBRL Taxonomy Extension Calculation LinkbaseDocument * 101.LAB XBRL Taxonomy Extension Label Linkbase Document * 101.PRE XBRL Taxonomy Extension Presentation LinkbaseDocument * 101.DEF XBRL Taxonomy Extension Definition LinkbaseDocument *^Confidential treatment has been granted with respect to redacted portions of this exhibit. Redacted portions of this exhibit have been filedseparately with the SEC. †A management contract or compensatory plan or arrangement required to be filed as an exhibit pursuant to Item 15(a)(3) of Form 10-K. *Filed herewith. **Furnished herewith.Exhibit 10.5(a) Execution copy CLINICAL TRIAL SERVICES AGREEMENT AMENDMENT NO. 8 TO WORK STATEMENT NB-1 RADIUS HEALTH, INC., a Delaware corporation (“ Radius ”) and NORDIC BIOSCIENCE CLINICAL DEVELOPMENT VII A/S, a Danish corporation (“ NB”) that is a wholly-owned subsidiary of Nordic Bioscience Clinical Development A/S entered into the certain Clinical Trial Services Agreement ( “Agreement” )and that certain Work Statement NB-1 under the Agreement as of March 29, 2011 ( “Effective Date” ), and entered into an Amendment No. 1, Amendment No. 2,Amendment No. 3, Amendment No. 4, Amendment No. 5, Amendment No. 6 and Amendment No. 7 to Work Statement NB-1 as of December 9, 2011, June 18,2012, November 6, 2013, March 28, 2014, May 19, 2014, July 22, 2014 and July 22, 2014 respectively, (as amended, “Work Statement NB-1” ). Pursuant to Section 2.3, 2.11 and 11.7 of the Agreement, the parties wish to enter into this Amendment No. 8 to Work Statement NB-1 ( “Amendment No. 8” )effective as of August 15, 2014 ( “Amendment Date” ). Capitalized terms used in this Amendment No. 8 and not defined herein are used with the meaningsascribed to them in the Agreement and Work Statement NB-1. NOW THEREFORE , in consideration of the mutual covenants and promises contained in this Amendment No. 8, the parties agree as follows: 1. End of Study Readiness Visits for BA058-05-003 : (a) At Radius request, NB will allocate resources as outlined below to perform additional activities to assist selected study sites for the end of the BA058-05-003Study in order to meet consistency in documentation across the sites. The purpose of this work statement is to allow NB the resources to visit selected sites andvendors to perform end of study readiness visits. Radius is responsible for selecting the sites targeted for these visits. (b) A new section at the bottom Attachment B to Work Statement NB-1 ( Budgets, Fees, Pass-through Costs, and Payment Schedule ) is hereby amended toread in full as follows: Budget Euro 11 days for Readiness Visits to selected sites, including reporting and follow up. Thesewill be performed by NB. €33.000 30 days allocated to accompany the Readiness Visits to selected sites for translation andsupport purposes. These will be performed by the local CRA’s. €75.000 TOTAL €108.000 (c) The “Payment Schedule” set forth in Attachment B to Work Statement NB-1 ( Attachment 2 to the Agreement) is amended to add a new Paragraph (16) immediately following Paragraph (15) of the Payment Schedule, which shall read in full as follows: “ Payment for End of Study Readiness Visits will be paid in 4 parts; 40% upon signing of this work statement, 30% after data base transfer in October, 2014, 15%when the database is soft locked and transferred to Radius in November 2014, and 15% when the data base is hard locked and transferred to Radius in December,2014. Such payments shall include all out-of-pocket travel expenses incurred by NB for study readiness visits ” 2.  Ratification.  Except to the extent expressly amended by this Amendment No. 8, all of the terms, provisions and conditions of the Agreement and WorkStatement NB-1 are hereby ratified and confirmed and shall remain in full force and effect. The term “Work Statement NB-1”, as used in the Agreement, shallhenceforth be deemed to be a reference to Work Statement NB-1 as amended by this Amendment No. 8. 1 3.  General.  This Amendment No. 8 may be executed in counterparts, each of which will be deemed an original with all such counterparts together constitutingone instrument. IN WITNESS WHEREOF the parties have caused this Amendment No. 8 under Work Statement NB-1 to be executed by their respective duly authorized officers,and have duly delivered and executed this Amendment No. 8 under seal as of the Amendment Date. RADIUS HEALTH, INC. NORDIC BIOSCIENCE CLINICAL DEVELOPMENT VII A/S /s/ R.E. Ward /s/ Jeppe Ragnar AndersenBy: R.E. Ward By:Title: President & CEO Title: CEO Notice Address Notice AddressRadius Health, Inc. Nordic Bioscience Clinical Development VII A/S950 Winter Street Herlev Hovedgade 207Waltham, MA 02451 2730 HerlevUSA DenmarkAttn: President & CEO Attn: CEOPhone: 01.617.551.4000 Phone: 45.4452.5251Fax: 01.617.551.4701 Fax: 45.4452.525 2Exhibit 10.7(c) CLINICAL TRIAL SERVICES AGREEMENT AMENDMENT NO. 4 TO WORK STATEMENT NB-3 RADIUS HEALTH, INC., a Delaware corporation (“ Radius ”) and NORDIC BIOSCIENCE CLINICAL DEVELOPMENT VII A/S, a Danish corporation (“ NB”) that is a wholly-owned subsidiary of Nordic Bioscience Clinical Development A/S entered into a Clinical Trial Services Agreement dated March 29, 2011 (“Agreement” ) and Work Statement NB-3 under the Agreement ( “Work Statement NB-3” ) as of February 21, 2013 ( “Effective Date” ), and entered into anAmendment No. 1, Amendment No. 2 and Amendment No. 3 to Work Statement NB-3 as of February 28, 2014, March 23, 2015 and July 8, 2015 (as amended,“Work Statement NB-3”). Pursuant to Section 2.3, 2.11 and 11.7 of the Agreement, the parties wish to enter into this Amendment No. 4 to Work Statement NB-3 ( “ Amendment No. 4” )effective as of October 21, 2015 ( “Amendment Date” ). Capitalized terms used in this Amendment No. 4 and not defined herein are used with the meaningsascribed to them in the Agreement and Work Statement NB-3. The purpose of this Amendment no. 4 is to include additional antibody procedure services and regulatory submission of Protocol No BA058-05-005, Amendment4, Version 1, August 24, 2015. NOW THEREFORE , in consideration of the mutual promises contained in the Agreement and for other good and valuable consideration the receipt andadequacy of which each of the parties does hereby acknowledge, the parties hereby agree to the terms of this Amendment No. 4 to Work Statement NB-3 asfollows: 1.  Additional Antibody Procedure Services: (a) At Radius’ request, NB will perform additional antibody procedure services (“Additional AB Services”) at CCBR and non-CCBR sites to monitor anypatients with positive antibodies in Radius’ BA058-05-005 clinical trial. (b) As part of the Additional AB Services, NB shall submit for regulatory approval Protocol No BA058-05-005, Amendment 4, Version 1, August 24, 2015to the relevant regulatory authorities and ethical committees. (c) Radius will compensate NB for the Additional AB Services and regulatory submissions as set forth in Attachment 1. This Amendment No. 4 to Work Statement NB-3 contains the following Attachments, each of which is made a part hereof: Attachment 1—Budget Summary including pricing, pass-through costs and PaymentScheduleAttachment 2—Protocol 2.  Payment Schedule Clarification. The parties agree to clarify that the Final Payment (15%) of 617,433.60 Euro (as set forth in Amendment No. 2 to WorkStatement NB-3) will be invoiced when the database is locked and transferred to and accepted by Radius and payable in accordance with the terms of theAgreement. Monthly Payments under Amendment No. 2 shall continue to be invoiced through March 2017. Provided that the trial master file is delivered to andaccepted by Radius before March 2017, the final remaining monthly payment(s) may be invoiced upon delivery. If the trial master file is delivered to and acceptedby Radius after March 2017, the final remaining monthly payment may not be invoiced until such delivery and acceptance has occurred. The trial master file isautomatically considered accepted for the purpose of invoicing 3 weeks after delivery, if no objections have been received. 3.  Ratification.  Except to the extent expressly amended by this Amendment No. 4, all of the terms, provisions and conditions of the Agreement and WorkStatement NB-3 are hereby ratified and confirmed and shall remain in full force and effect. The term “Work Statement NB-3” , as used in the Agreement, shallhenceforth be deemed to be a reference to Work Statement NB-3 as amended by this Amendment No. 4.  4.  General.  This Amendment No. 4 may be executed in counterparts, each of which will be deemed an original with all such counterparts together constitutingone instrument. IN WITNESS WHEREOF the parties have caused this Amendment No. 4 under Work Statement NB-3 to be executed by their respective duly authorized officers,and have duly delivered and executed this Amendment No. 4 under seal as of the Amendment Date.    RADIUS HEALTH, INC. NORDIC BIOSCIENCE CLINICAL DEVELOPMENT VII A/S /s/ Greg Williams /s/ Jeppe Ragnar AndersenBy:Greg Williams, PhD, MBA By: Title:Chief Development Officer Title: Nordic Bioscience Clinical Development Jeppe Ragnar Andersen, CEO Herlev Hovedgade 207 2730 Herlev Notice Address  Notice AddressRadius Health, Inc. Nordic Bioscience Clinical Development VII A/S201 Broadway, 6 Floor Herlev Hovedgade 205-207Cambridge, MA 02139 2730 HerlevUSA DenmarkAttn: President & CEO Attn: CEO, Jeppe Ragnar AndersenPhone: 01.617.551.4700 Phone: 45.4452.5252Fax: 01.617.551.4701 Fax: 45.4452.521 2 Attachment 1 - Budget  RADIUS    Antibody - BA058-05-003/005    Cost Proposal 21 October 2015    Sponsor:RADIUS Protocol ID:Antibody - BA058-05-003/005 Development Phase:N/A Disease:Osteoporosis Number of Countries:8 Number of Sites:18 Total BudgetEURO 1. Investigator Fee - Re-consent Informed Consent€150 per ICF re-consent 2. Investigator Fee - Blood sampling, scheduled visit€40 per scheduled visit 3. Investigator Fee - Blood sampling, unscheduled visit€96 per unscheduled visitEstimated 75% unscheduled visits4. Central Lab Fee (Synarc Lab)€26.40 per sampleShipment not included. Shipment to be invoiced as pass through5. Regulatory Submissions166.048Submission of amendment 4 to CA and EC’s6. Project management, coordination and oversight2.457 per month 7. Monitoring Visits, incl. travel cost45.000Includes up to 18 monitoring visits Pass through CostEURO TranslationIncluded in budget Travel Costs for Monitoring VisitsIncluded in budget Investigator MeetingNot included, will be pass-throughNo investigator meeting plannedLab shipmentsNot included, will be pass-throughEstimated 170.000 EURSubmission to EC and CAIncluded in budget EDC systemNot included, will be pass-throughExtra expense only if period extends beyond 005 Invoicing Schedule NB shall submit invoices to Radius in accordance with the following: Items 1-4 shall be invoiced on a monthly basis in accordance with work actually performed. Items 5 and 7, EUR 166,048 for Regulatory Submission and EUR 45,000 for Monitoring Visits, in total EUR 211,048, shall be paid as a non-refundable, upfrontpayment which falls due upon signing of this Amendment No. 4. th Item 6, Project Management Fees of EUR 2,457 shall be added to the amounts currently invoiced on a monthly basis until such time as the final lab sample hasbeen processed. 3 Attachment 2 - Protocol Protocol No BA058-05-005, Amendment 4, Version 1, August 24, 2015 to be supplied as a PDF. 4CLINICAL STUDY PROTOCOL An Extension Study to Evaluate 24 Months of Standard-of-Care Osteoporosis Management Following Completion of 18 Months of BA058 or PlaceboTreatment in Protocol BA058-05-003 This study will be conducted according to the protocol and in compliance with Good Clinical Practice, the ethical principles stated in the Declaration of Helsinki,and other applicable regulatory requirements. Protocol Number: Protocol BA058-05-005Protocol Date (Version): Original (23 July 2012) Amendment 1, Version 1 (13 February 2013) Amendment 2, Version 1 (31 March 2014) Amendment 3, Version 1 (3 March 2015) Amendment 4, Version 1 (24 August 2015)EudraCT Number 2012-002216-10IND Number: 73,176Study Sponsor: Radius Health, Inc. 950 Winter Street Waltham, MA 02451 Tel: 617.551.4000. Fax: 617.551.4701Sponsor Medical Lorraine A. Fitzpatrick, MDMonitor/Study Safety Chief Medical Officer, Radius Health, Inc.Officer: Tel: 617.551.4007. Fax: 617.551.4701. Email: XXXXXXXXXXXXXXXXXXXXXXXXXXXX Contract Research Nordic Bioscience A/SOrganization (CRO): Herlev Hovedgade 207 2730 Herlev, Denmark Tel: +45 4452 5252. Fax: +45 4452 5251 Disclosure StatementThis document contains information that is confidential and proprietary to Radius Health, Incorporated (RADIUS). This information is being provided to you solelyfor the purpose of evaluation and/or conducting a clinical trial for RADIUS. You may disclose the contents of this document only to study personnel under yoursupervision and/or to your institutional review board(s) or ethics committee(s) who need to know the contents for this purpose and who have been advised on theconfidential nature of the document.  Radius Health, Inc. Confidential PROTOCOL SYNOPSIS Title:  An Extension Study to Evaluate 24 Months of Standard-of-Care Osteoporosis Management Following Completion of 18 Months of BA058 or PlaceboTreatment in Protocol BA058-05-003 Protocol Number:  BA058-05-005 Test Drug:  Alendronate Study Objectives: Please note that the name of BA058 Injection 80 µg has been changed to Abaloparatide-SC, therefore the name has been changed throughout the document. The primary objective of this study is to collect clinical information regarding six months of treatment with alendronate, in subjects who have previously received18 months of blinded treatment with Abaloparatide-SC or Placebo in Study BA058-05-003. Safety data will be obtained via clinical, laboratory and radiologicassessments. Following the initial six months of treatment in the study, subjects will then enter the long-term observational phase of the study during whichsubjects will continue to receive alendronate treatment for an additional 18 months (for a total of 24 months). The specific objectives of this study are to: · Provide additional information on safety in study subjects receiving six months of treatment with alendronate following 18 months of treatment withAbaloparatide-SC/Placebo. · Provide information on the vertebral fracture rate in subjects receiving six months of treatment with alendronate following 18 months of treatment withAbaloparatide-SC/Placebo. · Provide additional information on non-vertebral fractures and BMD change associated with six months of treatment with alendronate following 18months of treatment with Abaloparatide-SC/Placebo. · Provide additional information on BMD change and osteoporosis status associated with 24 months of treatment with alendronate after 18 months oftreatment with Abaloparatide-SC/Placebo. The analysis performed at six months of this Extension Study will be used as a follow-up to the 18 month fracture endpoint for Study BA058-05-003. Vertebralfractures based on radiologic assessments will also be analyzed at Month 24. Additional analyses for other endpoints will be conducted cumulatively at Months 12,18, and 24 (i.e., Visits 4, 5, and 6). Full details of the statistical procedures to be used will be provided in the Statistical Analysis Plan. Study Population: Subjects with postmenopausal osteoporosis who completed the End-of-Treatment Visit (Visit 9) for Study BA058-05-003 and were previously randomized to eitherblinded Abaloparatide-SC or blinded Placebo are eligible for inclusion into this Extension Study provided that they fulfill the Inclusion/Exclusion criteria describedbelow. Inclusion/Exclusion Criteria Otherwise healthy ambulatory postmenopausal women who participated in, and who completed 18 months of treatment with either blinded Abaloparatide-SC orblinded Placebo in Study BA058-05-003, are scheduled to complete or have completed the End-of-Treatment visit (Visit 9 in Study BA058-05-003), and who haveprovided a new written informed consent for the Extension Study, are eligible for enrollment into this study. Participants must be no more than 40 days from Visit 9in Study BA058-05-003 to be eligible for this study. The physical examinations and clinical laboratory Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 2 Radius Health, Inc. Confidential measurements from the End-of-Treatment visit from Protocol BA058-05-003 (Visit 9) of the BA058-05-003 study will provide baseline data for this ExtensionStudy. In addition, the subjects must, in the opinion of the Investigator, be appropriate candidates for treatment with alendronate. Subjects will not be enrolled if they experienced a treatment-related SAE as assessed by the Investigator, or if they were withdrawn from Study BA058-05-003 forany reason. Specific inclusion and exclusion criteria are described in Section 4.1 and Section 4.2, respectively. Study Design and Methodology: Number of Subjects All subjects who were randomized to the Abaloparatide-SC/Placebo arms in Study BA058-05-003, and who completed 18 months of treatment will be offered theopportunity to participate in this study. There will, therefore, be a potential maximum of 1,600 subjects eligible to be enrolled in this study. Design This study will be an open-label extension of Study BA058-05-003. The purpose of the study is to provide longer term safety data, fracture data and BMD dataafter treatment with alendronate, in otherwise healthy ambulatory postmenopausal women with severe osteoporosis who have previously received 18 months ofblinded treatment with Abaloparatide-SC or Placebo. The analysis performed at six months will be used as a follow-up to the 18 month fracture endpoint for StudyBA058-05-003. In addition, this study will examine changes in osteoporosis status after 12, 18, and 24 months of treatment with alendronate in otherwise healthyambulatory women with severe osteoporosis who have previously received 18 months of blinded treatment with Abaloparatide-SC/Placebo. Subjects randomized to Abaloparatide-SC/Placebo in Study BA058-05-003 and who are candidates for alendronate treatment, will receive six months of treatmentwith oral alendronate at a total dose of 70 mg once per week. Following the initial six months of treatment in the study, subjects will then enter the long-termobservational phase of the study during which subjects will continue to receive alendronate treatment for an additional 18 months (for a total of 24 months). Allsubjects will undergo protocol specified procedures (Section 7.0, Appendix 14.1 and 14.2) including BMD and fracture assessment. The study design is presentedin Figure 1, below. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 3 Radius Health, Inc. Confidential Figure 1: Protocol BA058-05-005 Study Design In this study, the Follow-up Visit from the 18 month study (Visit 10 from Study BA058-05-003) will serve as the Day 1 Visit (Visit 1) for this six month ExtensionStudy (Study BA058-05-005). Following the initial six months of treatment, subjects will enter the long-term observational phase of this study during which the subjects will continue to receivealendronate treatment for an additional 18 months. During the long-term follow-up of this study, subjects will continue to undergo study related procedures asoutlined in Section 14.1 and Section 14.2. All subjects will continue to take calcium and vitamin D supplementation throughout the Extension Study. Study Visits At the End-of-Treatment Visit (Visit 9) for Study BA058-05-003, the possibility of participating in the Extension Study will be discussed with subjects randomizedto Abaloparatide-SC/Placebo. This Extension Study will be comprised of 24 months of treatment with alendronate. In the month between Visit 9 and Visit 10(between months 18 and 19 of Study BA058-05-003), the Investigator will consider the results of the assessments performed at Visit 9, including a local review ofBMD, and determine if alendronate is appropriate for the subject, as part of this Extension Study. At the Follow-up (Visit 10 for Protocol BA058-05-003, Day 1 for Protocol BA058-05-005) subjects; who were randomized to Abaloparatide-SC/Placebo, whofulfill the inclusion/exclusion criteria (Section 4.1 and Section 4.2), and who have agreed to participate in the Extension Study; will sign the Informed ConsentForm and be enrolled in the study. Subjects who have been determined by the Investigator to be candidates for alendronate therapy will receive open-label oral alendronate treatment at a total dose of70 mg once per week for 24 months. Subjects will be instructed to take their first dose of alendronate for Study BA058-05-005 in the morning, within a week oftheir Day 1 visit. Following the initial six months of treatment in this study, subjects will enter the long-term observational phase of this study, during whichsubjects will continue to receive alendronate treatment for an additional 18 months. All subjects will have clinic visits for study related procedures at Day 1, Month 3, Month 6, Month 12, Month 18 and Month 24. For the purpose of this study onemonth is equal to 30 days. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 4 Radius Health, Inc. Confidential Statistical Considerations: The statistical analyses will assess longer term safety, fracture incidence (including vertebral and non-vertebral fracture), and BMD change following treatmentwith alendronate for six months after the completion of a subject’s participation of 18 months in study BA058-05-003. The efficacy and safety analyses performed at six months will be used as a follow-up to the 18 month fracture endpoint for Study BA058-05-003. At this time-point, subjects will be analyzed based on the randomization assignment in the BA058-05-003 study. Fractures and BMD Analyses All specified endpoints will be summarized by treatment group and study period using standard descriptive statistics (n, mean, SD, median, minimum, maximum orn and %, as appropriate). The fracture incidence; either clinically or radiologically determined, based on clinical events or protocol-directed vertebral x-rays atMonth 6 of this Extension Study; will be analyzed. In addition, BMD results from the six months of treatment with alendronate will also be analyzed based on thetreatment arm they were randomized to in the BA058-05-003 study. These analyses will be conducted on all subjects with baseline and post-baseline data. In addition to the 6-month assessment, vertebral fractures based on radiologic assessments will also be analyzed at Month 24. Additional analyses for the otherendpoints will be cumulatively at Months 12, 18 and 24 (i.e., Visits 4, 5 and 6). Full details of these analyses will be provided in the Statistical Analysis Plan. Safety Analysis Data will be summarized and tabulated based on the enrolled population for this Extension Study. All subjects enrolled in the Extension Study will be included inthe safety analysis that will be performed on the following parameters: · Incidence and severity of AEs. · Pathological changes in hematology, chemistry and urinalysis data based on normal ranges supplied by the clinical laboratory, if applicable. Safety assessments for changes in physical examination, vital signs, ECG, and laboratory tests will be descriptively summarized by treatment and study periods.Concomitant medication classes will be categorized using World Health Organization (WHO) drug dictionary and summarized by number and percent of subjectsusing each class by treatment group. All treatment emergent adverse events (TEAEs) will be coded for system organ class (SOC) and preferred term (PT) usingMedDRA and the number (%) of subjects experiencing each AE (SOC/PT) will be summarized by treatment, relationship to treatment, and severity. All seriousadverse events (SAE) will be listed and the number (%) of subjects with an SAE presented by treatment group. Similar safety analyses will be conducted cumulatively at Months 12, 18, and 24 (i.e., Visits 4, 5, and 6). Full details of these analyses will be provided in theStatistical Analysis Plan. Procedures and Assessments Fractures and BMD The End-of-Treatment (Visit 9) evaluations for vertebral fracture assessment, non-vertebral fracture assessment and BMD from Study BA058-05-003 will serve asthe baseline evaluations in this study. The Day 1 assessment will be concurrent with the Follow-up Visit (Visit 10) for Study BA058-05-003. Subjects will return tothe clinic for assessment of BMD at spine, hip and wrist (for those subjects who had wrist DXAs performed in Study BA058-05-003) at Month 6, Month 12, Month18, and at Month 24. Any patient who shows a continuing significant deterioration (>7%) of BMD at Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 5 Radius Health, Inc. Confidential spine or hip from the Day 1 assessment of Study BA058-05-005 will have the assessment repeated and, if confirmed, will be discontinued from the study. Clinicaland radiographic assessments for fractures will be performed at Month 6 and Month 24, and bone marker assessments of anabolism (PINP, bone-specific alkalinephosphatase and osteocalcin) and resorption (CTX) will be performed at Day 1 and Months 6, 12, 18 and 24. Safety Safety evaluations performed will include physical examinations, vital signs, 12-lead ECGs, clinical laboratory tests, and monitoring and recording of adverseevents. Complete details of the study assessments are provided in Section 7.0, in the Schedule of Visits and Procedures (Appendix 14.1) and in the Suggested Schedule ofEvents and Procedures by Study Visit (Appendix 14.2). Treatments Administered Alendronate sodium (Fosamax®, Merck & Co., Inc., or other approved generic manufacturer) 70 mg tablets for oral administration contain 91.35 mg ofalendronate monosodium salt trihydrate which is the molar equivalent of 70 mg free acid and excipients. Alendronate should be stored in a well-closed container atroom temperature, 15-30ºC. The alendronate may be generic substitutable approved versions which contain different inactive ingredients, but the amount of activefree alendronate must be equivalent to 70 mg. Alendronate for Europe, Hong Kong and the US will be sourced centrally; alendronate for South America will besourced locally by the medical center and reimbursed by the Sponsor. However, alendronate may be locally sourced in all venues when centrally suppliedalendronate is unavailable due to unforeseen delays. The local source will be documented in the study drug logs. Calcium (500—1000 mg) and vitamin D (400—800 IU) supplements will be sourced locally by the medical center and provided to the subjects at the expense ofthe Sponsor. Subjects will continue to take calcium and vitamin D as they did in Study BA058-05-003. Duration of Subject Participation: Participation in the initial phase of this study will be approximately six months from enrollment to completion of the six month study evaluations. Participation forboth the initial and observational phases of the study will be approximately 24 months. In combination with Study BA058-05-003, subjects will participate in thisclinical postmenopausal osteoporosis program for 43 to 44 months. The first visit of Study BA058-05-005 will be concurrent with Visit 10 of Study BA058-05-003. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 6 Radius Health, Inc. Confidential TABLE OF CONTENTS PROTOCOL SYNOPSIS2  TABLE OF CONTENTS7  LIST OF ABBREVIATIONS10   1.0INTRODUCTION12 1.1BACKGROUND INFORMATION121.2DRUG UNDER STUDY121.2.1Efficacy of Alendronate121.2.2Safety of Alendronate Sodium131.3STUDY RATIONALE AND SELECTION OF DOSES141.3.1Study Rationale141.3.2Study Design141.3.3Study Population151.3.4Selection of Endpoints151.3.5Selection of Dose15 2.0STUDY OBJECTIVES15   3.0INVESTIGATIONAL PLAN16 3.1OVERALL DESIGN AND STUDY PLAN163.1.1Treatment Period17 4.0SELECTION OF STUDY POPULATION18 4.1NUMBER OF SUBJECTS184.2INCLUSION CRITERIA184.3EXCLUSION CRITERIA194.4WITHDRAWAL OF SUBJECTS FROM THE STUDY194.5TEMPORARY SUSPENSION OF TREATMENT194.6REPLACEMENT OF SUBJECTS20 5.0STUDY TREATMENTS20 5.1STUDY MEDICATIONS205.1.1Alendronate205.1 . 1.1Restrictions on Alendronate Use205.1.2Calcium and Vitamin D Supplements205.2PACKAGING, LABELING AND STORAGE205.2.1Storage215.3TREATMENT ASSIGNMENT215.4STUDY MEDICATION ADMINISTRATION215.4.1Alendronate Administration215.5TREATMENT COMPLIANCE215.6UNBLINDING OF STUDY MEDICATION21 6.0CONCOMITANT MEDICATIONS22 6.1CONCOMITANT MEDICATIONS226.2PROHIBITED MEDICATIONS22   7.0STUDY ASSESSMENTS22 7.1CLINICAL PROCEDURES/ASSESSMENTS237.1.1Informed Consent237.1.2Recent Health Status237.1.3Vital Signs237.1.4Height and Weight237.1.5Orthostatic Blood Pressure and Heart Rate23 Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 7 Radius Health, Inc. Confidential 7.1.6Electrocardiogram237.1.7Clinical Laboratory Evaluations247.1.8Clinical Chemistry and Urinalysis (Dipstick)247.1.9Hematology257.1.10Coagulation257.1.1124-Hour Urine Collection257.1.12Bone Mineral Density257.1.13Serum Markers of Bone Metabolism267.1.14Clinical and Radiologic Evaluation of Fractures267.1.15Abaloparatide Antibody Assessments267.1.16Subject Diaries277.1.17Activity and Diet27 8.0ADVERSE EVENTS AND SAFETY EVALUATION27 8.1DEFINITIONS, DOCUMENTATION, AND REPORTING278.1.1Adverse Event Definition278.1.2Serious Adverse Event Definition278.2MONITORING OF ADVERSE EVENTS AND PERIOD OF OBSERVATION288.3PROCEDURES FOR RECORDING AND REPORTING AES AND SAES288.4RULES FOR SUSPENSION OF THE STUDY30   9.0STATISTICAL PROCEDURES30 9.1SAMPLE SIZE319.2RANDOMIZATION, STRATIFICATION AND BLINDING319.3POPULATIONS FOR ANALYSIS319.3.1ITT (Safety) Population319.3.2Modified Intent-to-Treat Population319.3.3Per Protocol Population319.4PROCEDURES FOR HANDLING MISSING, UNUSED, AND SPURIOUS DATA319.5STATISTICAL METHODS319.5.1Statistical Considerations319.5.2Baseline Comparisons329.5.3Fractures and BMD Analysis329.5.4Safety Analysis329.5.5Procedures for Reporting Deviations to Original Statistical Analysis Plan329.6DATA OVERSIGHT339.6.1Central Review of Radiographs and DXA Scans33 10.0ADMINISTRATIVE REQUIREMENTS33 10.1GOOD CLINICAL PRACTICE3310.2ETHICAL CONSIDERATIONS3310.3SUBJECT INFORMATION AND INFORMED CONSENT3310.4PROTOCOL COMPLIANCE3410.5CASE REPORT FORM COMPLETION3410.6SOURCE DOCUMENTS3410.7STUDY MONITORING3510.8ON-SITE AUDITS3510.9DRUG ACCOUNTABILITY3510.10RECORD RETENTION3510.11STUDY TERMINATION3610.12LIABILITY AND INSURANCE36   11.0USE OF INFORMATION AND PUBLICATION OF STUDY FINDINGS36 11.1USE OF INFORMATION3611.2PUBLICATION37 Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 8 Radius Health, Inc. Confidential    12.0INVESTIGATOR AGREEMENT3813.0REFERENCES3914.0APPENDICES4114.1SCHEDULE OF VISITS AND PROCEDURES4214.2SUGGESTED SCHEDULE OF EVENTS AND PROCEDURES BY STUDY VISIT4414.3EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) COMMON TOXICITY CRITERIA52 Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 9 Radius Health, Inc. Confidential LIST OF ABBREVIATIONS Abbreviation Term°C Degree Celsius°F Degree Fahrenheitµg Microgramµmol MicromoleAE Adverse eventALT Alanine aminotransferaseAST Aspartate aminotransferaseBMD Bone mineral densityBMI Body mass indexbpm Beats per minuteBSAP Bone-specific alkaline phosphataseBUN Blood urea nitrogencm CentimeterCPK Creatine phosphokinaseCRF Case report formCRO Contract research organizationCTX C-telopeptides of type 1 collagen crosslinks (serum)DXA Dual energy x-ray absorptiometryECG ElectrocardiogrameCRF Electronic case report formFDA Food and Drug Administrationg GramGCP Good clinical practiceGGT Gamma-glutamyltranspeptidaseGLP Good laboratory practiceGMP Good manufacturing practiceICH International Conference on HarmonizationIEC Independent ethics committeeIRB Institutional review boardITT Intent-to-treatIU International unitIV IntravenousIVRS Interactive voice response systemkg KilogramL LiterLDH Lactate dehydrogenaseMCH Mean corpuscular hemoglobinMCHC Mean corpuscular hemoglobin concentrationMCV Mean corpuscular volume Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 10 Radius Health, Inc. Confidential Abbreviation TermMedDRA Medical dictionary for regulatory activitiesµL Microlitermg MilligrammL MillilitermmHg Millimeter of mercurymsec MillisecondNPO Nothing by mouthng NanogramONJ Osteonecrosis of the jawPA Posterior-anteriorPD Pharmacodynamicpg PicogramPINP N-terminal propeptide of type I procollagenPK PharmacokineticPT Prothrombin timePTH Parathyroid hormonePTHrP Parathyroid hormone related peptidePTT Partial thromboplastin timePUBs Upper gastrointestinal perforations, ulcers and bleedsQT Total depolarization and repolarization timeQTc Total depolarization and repolarization time corrected with heart rateRBC Red blood cellSAE Serious adverse eventSC SubcutaneousSD Standard deviationSERMs Selective estrogen receptor modulatorsSOC System organ classSOP Standard operating procedureTEAEs Treatment emergent adverse eventsULN Upper Limit of NormalWBC White blood cellsWHO World Health Organization Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 11 Radius Health, Inc. Confidential 1.0  INTRODUCTION 1.1  Background Information Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue which leads to enhanced fragilityand increased risk of fractures (Rizzoli, 2001). It is estimated that over 200 million people worldwide have osteoporosis (Reginster, 2006) and osteoporosis causesmore than 8.9 million fractures worldwide, of which more than 4.5 million occur in the Americas and Europe (WHO Scientific Group, 2007). The vast majority ofosteoporotic fractures occur in elderly women and incidence increases markedly with age. Most fractures occur at the spine, wrist and hip. Of these, hip fracturescarry the highest morbidity and mortality. In 1990, the total number of hip fractures in men and women was estimated to be 1.26 million worldwide, and it isestimated that this number will increase to 3.6 million by 2025 and to 4.5 million by 2050 (Gullberg, 1997). Subjects enrolled in this Extension Study will have completed 18 months of treatment with Abaloparatide-SC/Placebo. Abaloparatide is a synthetic 34 amino acidanalog of parathyroid hormone related peptide(PTHrP), with molecular modifications of specific amino acids, and is under clinical development for the preventionof fractures in postmenopausal women with severe osteoporosis who are at a risk for fracture. Abaloparatide shows particular potential for reversing bone loss atboth the spine and the hip, the site of the most debilitating osteoporotic fractures in elderly women. Abaloparatide is a synthetic analog of PTHrP (1-34) designed togive a greater anabolic effect than human parathyroid hormone (hPTH). Initial in vitro and in vivo studies identified abaloparatide as displaying bone anabolicproperties without a significant hypercalcemic effect. In humans, abaloparatide has different pharmacokinetics (PK) and pharmacodynamics (PD) properties thanhPTH(1-34) and has been shown in a Phase 2 study (BA058-05-002) to have similar or greater efficacy in restoring bone mineral density (BMD) in individualswith osteoporosis than hPTH(1-34). Overall, abaloparatide has been well tolerated in previous studies. This is an open-label extension of Study BA058-05-003. Enrollment requires previous participation in, and successful completion of, 18 months of treatment withAbaloparatide-SC/Placebo in Study BA058-05-003. The purpose of this extension is to accumulate longer-term safety, fracture, and BMD data in subjects whoreceive six months of treatment with alendronate, following 18 months of treatment with blinded Abaloparatide-SC/Placebo treatment. Following the initial sixmonths of treatment in this study, subjects will then enter the long-term observational phase of this study during which the subjects will continue to receivealendronate treatment for an additional 18 months. The analyses performed at six months will be used as a follow-up to the 18 month fracture endpoint for StudyBA058-05-003. Additional analyses will be cumulatively at Months 12, 18, and 24 (i.e., Visits 4, 5, and 6. Full details of the statistical procedures to be used willbe provided in the Statistical Analysis Plan. Alendronate, a bisphosphonate, is approved and marketed world-wide for the treatment and prevention of osteoporosisin postmenopausal women. 1.2  Drug Under Study 1.2.1 Efficacy of Alendronate Alendronate is a bisphosphonate that acts as a specific inhibitor of osteoclast-mediated bone resorption. Bisphosphonates are synthetic analogs of pyrophosphatethat bind to the Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 12 Radius Health, Inc. Confidential hydroxyapatite found in bone. At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. Theosteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate does not interfere with osteoclastrecruitment or attachment, but it does inhibit osteoclast activity. (Fosamax Package Insert) Bisphosphonates including alendronate are widely used to treat osteoporosis. In animal models, minipigs treated with alendronate exhibited a direct correlationbetween cancellous bone volume and bone strength (Lefage 1995). In primates, treatment with alendronate increased the strength of cancellous bone between 44and 100% (the effect was dose dependent) when compared to vehicle, and also increased bone mass (Balena 1993). In dogs, this increase in bone mass occurredwithout causing abnormalities in bone modeling of bone structure (Balena, 1996). In postmenopausal women, alendronate has been demonstrated to increase bone mineral density, decrease bone turnover and reduce the risk of fracture amongwomen with osteoporosis (Tucci, 1996; Devogelaer, 1996; Liberman, 1995). The therapeutic effects on bone density, remodeling and fracture prevention persistfollowing daily treatment at an oral dose of 10 mg for up to 10 years (Bone, 2004). Studies have demonstrated that sequential treatment of osteoporosis with oneyear of treatment with PTH followed by one year of treatment with alendronate resulted in an increase in vertebral bone density that was considerably greater thanpreviously reported for alendronate alone (Rittmaster, 2000). In subjects receiving PTH(1-84) followed by alendronate, there were significant increases in BMD, inparticular trabecular spine, when compared to PTH(1-84) followed by placebo (31% vs. 14%, p<0.001) (Black, 2005). 1.2.2 Safety of Alendronate Sodium According to the US package insert for Fosamax® (alendronate sodium), in studies of up to five years duration, adverse experiences usually were mild andgenerally did not require discontinuation of therapy. In a three-year, placebo-controlled, double blind study in which 196 subjects were treated with 10 mg/day,discontinuation due to any adverse experience occurred in 4.1% of subjects treated with alendronate, and 6% of 397 subjects treated with placebo. The mostfrequently reported adverse event (occurring in > 2% of subjects treated with alendronate) in this study were abdominal pain, musculoskeletal pain, nausea,dyspepsia, constipation, diarrhea, flatulence, headache and acid regurgitation. Alendronate may cause local irritation of the upper gastrointestinal mucosa. Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophagealerosions occasionally with bleeding and rarely followed by esophageal stricture or perforation have been reported. Osteonecrosis of the jaw (ONJ), which can occurspontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, has been reported in subjects taking alendronate. Forsubjects requiring dental procedures, discontinuation of alendronate therapy may reduce the risk for ONJ. Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in thefemoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence ofcomminution. Causality has not been Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 13 Radius Health, Inc. Confidential established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates. Atypical femur fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain inthe affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were alsoreceiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should beevaluated to rule out an incomplete femur fracture. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in thecontralateral limb. Interruption of bisphosphonate therapy should be considered, pending a risk/benefit assessment, on an individual basis. According to the Summary of Product Characteristics for alendronate from the EMA, the following adverse experiences have been reported in alendronate treatedsubject during clinical trials and/or post-marketing use: Common: Headache, abdominal pain, dyspepsia, constipation, diarrhea, flatulence, esophageal ulcer, dysphagia, abdominal distension, acid regurgitation andmusculoskeletal pain. Uncommon: Nausea, vomiting, gastritis, esophagitis, esophageal erosions, melena, rash, pruritus and erythema. Rare: Hypersensitivity reactions including urticarial and angioedema, symptomatic hypocalcemia (often in association with predisposing conditions), uveitis,scleritis, episcleritis, esophageal stricture, oropharyngeal ulceration, upper gastrointestinal perforations, ulcers and bleeds (PUBs), rash with photosensitivity,osteonecrosis of the jaw, atypical subtrochanteric and diaphyseal femoral fractures and transient symptoms as in an acute-phase response (myalgia, malaise andrarely, fever), typically associated with initiation of treatment. 1.3  Study Rationale and Selection of Doses 1.3.1 Study Rationale The purpose of the study is to provide longer term safety data, fracture data and BMD data after six months of treatment with alendronate, in otherwise healthyambulatory postmenopausal women with severe osteoporosis who have previously received 18 months of blinded treatment with Abaloparatide-SC or Placebo.Following the initial six months of treatment in this study, subjects will enter the long-term observational phase of the study during which the subjects will continueto receive alendronate for an additional 18 months. 1.3.2 Study Design Subjects randomized to Abaloparatide-SC/Placebo, who have completed 18 months of treatment in Protocol BA058-05-003 and, who meet the Inclusion/Exclusioncriteria (Sections 4.2 and 4.3) are eligible to participate in this study. Subjects originally randomized to Abaloparatide-SC/Placebo in Study BA058-05-003 andwho are candidates for ongoing Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 14 Radius Health, Inc. Confidential osteoporosis care, will receive 24 months of weekly open-label alendronate treatment at a dose of 70 mg/week. 1.3.3 Study Population The study population in this protocol is comprised of otherwise healthy ambulatory postmenopausal women who: 1. have participated in Study BA058-05-003, 2. were randomized to either Abaloparatide/Placebo, 3. have completed the End-of-Treatment Visit (Visit 9 in Study BA058-05-003), and 4. have provided a new written informed consent for this protocol. Subjects will not be enrolled if they experienced treatment-related SAE or were withdrawn from Study BA058-05-003 for any reason. 1.3.4 Selection of Endpoints The fracture incidence; either clinically or radiologically determined, based on clinical events or protocol-directed vertebral x-rays at Month 6 of this ExtensionStudy; will be analyzed. In addition, BMD results from the six months of treatment with alendronate will also be analyzed. Bone formation (PINP, osteocalcin,BSAP) and resorption (CTX) markers will also be assessed. Clinical incidence of any fracture and radiologic incidence of vertebral fracture will also be evaluatedat Month 24. The End-of-Treatment (Visit 9) evaluations for BMD, vertebral fracture, and non-vertebral fracture assessments from BA058-05-003 will serve as thebaseline evaluations in this study. In addition to the 6-month assessment, clinical and radiologic assessment of the spine for assessment of fractures will be performed at Month 24. At Months 6, 12,18 and 24, BMD by DXA, as well as clinical assessments of fractures will be performed. Bone formation and resorption markers will also be assessed at Day 1 andMonths 6, 12 18 and 24. Further details of these assessments are in Section 7.0, and in Appendix 14.1 and 14.2. Subjects will be monitored for safety events and will have safety assessments performed at each study visit. 1.3.5 Selection of Dose The dose of alendronate (70 mg per week, oral) selected for this study is based upon the recommended daily dose in the product’s prescribing information. All enrolled subjects will also continue to receive calcium (500-1000 mg) and vitamin D (400-800 IU) supplementation. 2.0  STUDY OBJECTIVES The primary objective of this study is to evaluate data obtained following six months of treatment with alendronate, in subjects who have previously received 18months of blinded Abaloparatide -SC/Placebo. Safety will be evaluated with clinical, laboratory and radiologic assessment. The analysis at six months will bebased on the treatment that subjects were randomized to in the BA058-05-003 study. Following the initial six months of treatment in this study, subjects will thenenter the long-term observational phase of the study during Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 15 Radius Health, Inc. Confidential which the subjects will continue to receive alendronate treatment for an additional 18 months. The specific objectives of this study are to: · Provide additional information on safety in study subjects receiving six months of treatment with alendronate following 18 months of treatment withAbaloparatide-SC/Placebo. · Provide information on the vertebral fracture rate in subjects receiving six months of treatment with alendronate following 18 months of treatment withAbaloparatide-SC/Placebo. · Provide additional information on non-vertebral fractures and BMD change associated with six months of treatment with alendronate following 18months of treatment with Abaloparatide-SC/Placebo. · Provide additional information on BMD change and osteoporosis status associated with 24 months of treatment with alendronate after 18 months ofAbaloparatide-SC/Placebo. The analysis performed at six months will be used as a follow-up to the 18 month fracture endpoint for Study BA058-05-003. Vertebral fractures based onradiologic assessments will also be analyzed at Month 24. Additional analyses for other endpoints will be conducted cumulatively at Months 12, 18, and 24 (i.e.,Visits 4, 5, and 6). Full details of the statistical procedures to be used will be provided in the Statistical Analysis Plan. 3.0  INVESTIGATIONAL PLAN 3.1  Overall Design and Study Plan This study is an open-label extension of Study BA058-05-003. Subjects and Investigators who participate in Study BA058-05-005 will remain blinded to priortreatment assignment as part of BA058-05-003. At the End-of-Treatment visit (Visit 9) for Study BA058-05-003, the possibility of participating in the ExtensionStudy will be discussed with subjects randomized to Abaloparatide-SC/Placebo. The Extension Study will be comprised of an initial six months of treatment withalendronate. In the month between Visit 9 and Visit 10, the Investigator will review the results of the assessments performed at Visit 9, including a localinterpretation of BMD, and determine if alendronate is appropriate for the subject. All subjects will continue to receive vitamin D and calcium supplementation asthey did in Study BA058-05-003. The study design is presented in Figure 2, below. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 16 Radius Health, Inc. Confidential Figure 2: Protocol BA058-05-005 Study Design Participation for both the initial and observational phases of the will be approximately 24 months. There are a total of six clinic visits during the course of the study. A brief summary of the study is provided below. For a summary of the study assessments to be performed, refer to Section 7.0 (Study Assessments) and to theSchedule of Visits and Procedures (Appendix 14.1). A more detailed description of the study procedures on a by-visit basis is provided in Appendix 14.2(Suggested Schedule of Events and Procedures by Study Visit). A suggested order of procedures is also provided in this schedule. 3.1.1 Treatment Period Subjects will enter into Study BA058-05-005 on Day 1, and Day 1 will also serve as Visit 10 (the Follow-up Visit) for Study BA058-05-003. The InformedConsent must be signed prior to undergoing any BA058-05-005 study related procedures, and may be signed at either Visit 9 or Visit 10 of Study BA058-05-003.Subjects who received Abaloparatide-SC/Placebo in Study BA058-05-003 will receive six months of open-label oral alendronate treatment as part of this study(BA058-05-005). Following the initial six months of treatment in this study, subjects will then enter the long-term observational phase of this study during whichthe subjects will continue to receive alendronate care for an additional 18 months. If determined by the Investigator to be appropriate, treatment will be by oral administration of alendronate at a total dose of 70 mg once per week. Subjects will begiven a weekly diary card to record missed doses of medication including calcium and vitamin D. A total of six clinic visits are scheduled during the study (Day 1, Month 3, Month 6, Month 12, Month 18 and Month 24). Subjects will be instructed to take their first dose of study drug for Study BA058-05-005 in the morning, within a week of their Day 1 visit (Day 2 of this study).Study subjects will Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 17 Radius Health, Inc. Confidential continue calcium and vitamin D supplementation during this study as was administered during BA058-05-003 (Section 6.1). At Month 3, subjects will return to the clinic for medication resupply, subject diary review and questioning as to their use of concomitant medications and theoccurrence of adverse events. At the Month 6 visit ECG, and safety labs will be performed. Vertebral fractures will be determined clinically and via protocol directed x-ray evaluation; non-vertebral fractures will be determined clinically. In addition, subjects will undergo a DXA of the hip and spine (and wrist, if the subject was enrolled in the wristDXA sub-study in Study BA058-05-003), and have samples drawn for bone markers and anti-abaloparatide antibodies. Procedures are to be performed as describedin Section 7.0, Appendix 14.1 and Appendix 14.2. At Months 12 and 18, subjects will return to the clinic for safety labs, DXA of the hip and spine (and wrist, if the subject was enrolled in the wrist DXA sub-studyin Study BA058-05-003), medication resupply, subject diary review and questioning as to their use of concomitant medications and occurrence of adverse events.Serum samples for bone markers will also be drawn. At Month 24, subjects will return to the clinic for safety labs, and will undergo clinical and radiologic fracture assessments and have DXA of the hip and spine (andwrist, if the subject was enrolled in the wrist DXA sub-study in Study BA058-05-003). Serum samples for bone markers will also be drawn. Any adverse event orclinical laboratory abnormality recorded at the Month 24 Visit will be monitored until it has resolved, become chronic or stable. 4.0  SELECTION OF STUDY POPULATION 4.1  Number of Subjects Subjects who completed 18 months of treatment with either Abaloparatide-SC/Placebo in Study BA058-05-003 will be given the opportunity to participate in theExtension Study at all participating centers. Based on randomization to the Abaloparatide-SC/Placebo arms in Study BA058-05-003, up to 1,600 subjects may beentered into this study. The specific inclusion and exclusion criteria for enrolling subjects in this study are presented below in Sections 4.2 and 4.3, respectively. Exceptions to thesecriteria should occur infrequently and should be discussed in advance and approved by the Sponsor Medical Monitor. 4.2  Inclusion Criteria Subjects must meet all of the following criteria to be eligible to participate in this study: 1. The subject was enrolled, randomized to Abaloparatide-SC/Placebo and completed 18-months of blinded treatment within Study BA058-05-003. 2. The subject is no more than 40 days from Visit 9 in Study BA058-05-003. 3. The subject has read, understood, and signed the written informed consent form for the Extension Study. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 18 Radius Health, Inc. Confidential 4.3  Exclusion Criteria Subjects with any of the following characteristics are not eligible to participate in the study: 1. Subjects who were withdrawn from Study BA058-05-003 for any reason. 2. Subjects who experienced a treatment-related SAE during Study BA058-05-003. 4.4  Withdrawal of Subjects from the Study Subjects will be informed that they have the right to withdraw from the study at any time for any reason without prejudice to their medical care. Consistent with the prior protocol, BA058-05-003, the Investigator must withdraw subjects from the study prior at any time in the study for the following reasons: · Continuing significant deterioration from the Day 1 assessment of Study BA058-05-005 (>7%) of BMD at spine or hip (after confirmation of thefinding); · Treatment-related SAEs; · Refusal of treatment; · Refusal or inability to complete study procedures; · Lost to follow-up. The Investigator should exercise his/her best judgment and also has the right to withdraw subjects from the study during the study for any of the following reasons: · ECOG Grade 3 or 4 adverse events [Refer to Appendix14.3]; · A complex of adverse events which, in the judgment of the Investigator justifies treatment cessation; · Serious intercurrent illness; · Non-compliance; · Protocol violations; · Administrative reasons. If a subject is withdrawn or discontinued from the study, the reason for withdrawal is to be recorded in the source documents and on the case report form. Allsubjects withdrawn prior to completing the study should be encouraged to complete the Month 6 or Month 24 Visit (depending on the length of time on study)including any outstanding radiologic assessment or BMD assessment by DXA. 4.5  Temporary Suspension of Treatment The Investigator has the right to suspend treatment with alendronate without withdrawal of the subject from the study. Reasons for temporary suspension oftreatment may include a medical reason unrelated to an adverse event (e.g., a planned procedure), or important social or administrative events. The reason for thesuspension of treatment is to be documented in the electronic case report form (eCRF) and in source documents. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 19 Radius Health, Inc. Confidential When treatment with alendronate is restarted, the subject should resume treatment with the next scheduled dose (as if treatment had not been interrupted). 4.6  Replacement of Subjects Subjects who have been enrolled into the study and subsequently withdraw or drop out of the study will not be replaced. 5.0  STUDY TREATMENTS 5.1  Study Medications Alendronate will be sourced locally. Calcium and vitamin D will be provided by the study centers, similar to their provision in Study BA058-05-003. 5.1.1 Alendronate Alendronate will be sourced centrally for Europe, Hong Kong and the US, and will be sourced locally for South America at the expense of the Sponsor. However,alendronate may be locally sourced in all venues when centrally supplied alendronate is unavailable due to unforeseen delays. The local source will be documentedin the study drug logs. Subjects will receive oral alendronate at a dose of 70 mg once per week beginning on Day 2 for 24 months. Additional provisions for dosing of alendronate shouldbe followed based on the prescribing information. Alendronate provided will be in the approved, marketed formulation. The alendronate may be genericsubstitutable approved versions which contain different inactive ingredients, but the amount of active free alendronate must be equivalent to 70 mg per week. 5.1.1.1 Restrictions on Alendronate Use Subjects should not receive alendronate if they have the following conditions/limitations: · Abnormalities of the esophagus and other factors which delay esophageal emptying such as stricture or achalasia. · Inability to stand or sit upright for at least 30 minutes. · Hypocalcemia. · Known history of hypersensitivity to alendronate, alendronate excipients, or related compounds. 5.1.2 Calcium and Vitamin D Supplements Calcium and vitamin D supplements will be sourced locally and provided by the sites at the expense of the Sponsor. 5.2  Packaging, Labeling and Storage Centrally supplied alendronate will not be repackaged for the study, but will be over-labeled according to local regulatory requirements as necessary. Calcium and vitamin D supplements will not be relabeled for the study. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 20 Radius Health, Inc. Confidential 5.2.1 Storage Alendronate must be kept in a secure, limited-access storage area until dispensed for use to a study subject. Alendronate sodium should be stored in the containerprovided at room temperature, 15-30ºC (59-86ºF). Calcium and vitamin D supplements may be stored at room temperature. 5.3  Treatment Assignment All subjects who participate will continue to be identified by the same 7-digit subject number that was assigned upon enrollment into Study BA058-05-003throughout the study and on the eCRF. 5.4  Study Medication Administration 5.4.1 Alendronate Administration Alendronate must be taken with water only (not mineral water) at least 30 minutes before the first food, beverage or medicinal product (including antacids, calciumsupplements and vitamins) of the day. Other beverages (including mineral water), food and some medicinal products are likely to reduce the absorption ofalendronate. The following instructions should be followed exactly in order to minimize the risk of esophageal irritation and related adverse reactions. · Alendronate should only be swallowed after getting up for the day with a full glass of water (not less than 200 mL or 7 fl. oz.).· Subjects should only swallow alendronate whole. Subjects should not crush or chew the tablet or allow the tablet to dissolve in their mouths because of apotential for oropharyngeal ulceration.· Subjects should not lie down until after their first food of the day.· Subjects should not lie down for at least 30 minutes after taking alendronate.· Alendronate should not be taken at bedtime or before arising for the day. At the Month 3, Month 6, Month 12 and Month 18 visits, the unused alendronate tablets are to be returned to the clinic for counting and the subject will bedispensed additional alendronate. At the Month 24 visit, all unused alendronate tablets are to be returned to the study site. 5.5  Treatment Compliance The study site personnel will perform drug accountability at each clinic visit and review each subject diary (refer to Section 7.1.16). Accountability will bedocumented on the appropriate forms and subjects will be re-trained on administration as appropriate. All doses of study medication are to be self-administered. If a subject does not administer or take all study medication including vitamin D or calcium, the reason for the missed dosing is to be recorded in source documentsand on the eCRF. Returned, unused alendronate will be accounted for by the study site and destroyed as appropriate. 5.6  Unblinding of Study Medication Not applicable. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 21 Radius Health, Inc. Confidential 6.0  CONCOMITANT MEDICATIONS 6.1  Concomitant Medications Vitamin D and calcium supplements are required to be administered daily from Day 1 (continuing from Protocol BA058-05-003) until the Month 6 Visit. VitaminD and calcium supplements will be administered in the following doses: 400-800 IU/day (Vitamin D) and 500-100mg/day (calcium), or at a dose to be determinedby the Investigator according to the subjects need. The doses and schedule of Vitamin D and calcium supplements, which are part of the study medication protocol,should be adhered to and not be changed other than for medical necessity. The supplements should be taken in the evening with or without food or as otherwiseinstructed by the Investigator. For any required concomitant medication, such as statins or antihypertensives, the subject must be on a stable dose at study entry and every effort should be madeto maintain a stable dose during study participation. The occasional use of over-the-counter medications at approved doses (e.g., ibuprofen or acetaminophen) for headache or minor discomfort is allowed. Occasionalshort term ( < 3 months) use of corticosteroids for seasonal allergies or asthma is also allowed. These are to be recorded on the appropriate case report form.Subjects should not take any other medications, including over-the-counter medications, herbal medications, or mega-doses of vitamins during the study withoutprior approval of the Investigator. If it becomes necessary for a subject to take any other medication during the study, the specific medication(s) and indication(s) must be discussed with theInvestigator. All concomitant medications taken during the course of the study must be recorded in the Subject’s medical record or source document andtranscribed into the case report form. 6.2  Prohibited Medications Subjects who require treatment during the course of the study with either an anticonvulsant (phenobarbital, phenytoin, carbamazepin or primidone) or chronictreatment with any form of heparin will be discontinued. Estrogens given as HRT are allowed at entry into the study but cannot be initiated during the study exceptfor local low dose vaginal estrogen. Drugs that may compromise renal function such as non-steroidal anti-inflammatory drugs should be used with caution. 7.0  STUDY ASSESSMENTS Subjects randomized to Abaloparatide-SC/Placebo in Study BA058-05-003 will receive alendronate at a dose of 70 mg once per week for a total of 24 months. The assessments performed at each study visit are displayed in the Schedule of Visits and Procedures in Appendix 14.1. Appendix 14.2 provides a more detailedschedule of the study procedures by study visit with a suggested order of procedure conduct. Exact procedures for centrifuging, storage, and shipping of laboratorysamples will be detailed in a separate document. The actual time of each blood collection will be recorded on the appropriate source documents and in the eCRF. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 22 Radius Health, Inc. Confidential Study-specific assessments are to be conducted only after the subject has provided written informed consent to participate in this study. The study assessments aredescribed in more detail in Section 7.1 below. 7.1  Clinical Procedures/Assessments 7.1.1 Informed Consent At the End-of-Treatment Visit (Visit 9) for Study BA058-05-003, the possibility of participating in the Extension Study will be discussed with the subjectsrandomized to Abaloparatide-SC/Placebo. The Informed Consent must be signed prior to undergoing any BA058-05-005 study related procedures, and may besigned at either Visit 9 or Visit 10 of Study BA058-05-003. 7.1.2 Recent Health Status The subject’s health status will be updated from their last visit in Study BA058-05-003, as necessary. Any changes in health status should be recorded as an adverseevent, as appropriate. The physical examination from the End-of-Treatment visit (Visit 9) of Study BA058-05-003 will be the baseline for this study (Day 1). Interim or symptom-directed physical examinations may be performed at the discretion of the Investigator, if necessary, to evaluate adverse events or clinicallaboratory abnormalities. 7.1.3 Vital Signs Blood pressure, body temperature (ºC), pulse (bpm) and respiration rate (breaths per minute) are to be measured and recorded at each study visit (Day 1, Month 3and Month 6, Month 12, Month 18 and Month 24). Only the Day 1 blood pressure assessments need be conducted as an orthostatic measurement (SeeSection 7.1.5). 7.1.4 Height and Weight Height and weight are to be measured at each study visit (Day 1, Month 3, Month 12, Month 18 and Month 24). Height is to be measured in the standing positionusing a medical stadiometer. 7.1.5 Orthostatic Blood Pressure and Heart Rate The Day 1 orthostatic blood pressure measurement for Study BA058-05-005 will serve as the Visit 10 orthostatic blood pressure for Study BA058-05-003. Bloodpressure (mmHg; measured in the same arm at each visit) and pulse rate (bpm) will be measured after five minutes in the supine position. Immediately followingthis measurement, blood pressure will be measured again after three minutes in the standing position. 7.1.6 Electrocardiogram A twelve-lead supine electrocardiograms (ECGs) will be performed and the following ECG parameters will be recorded: rhythm, heart rate, PR interval, QRSduration and QT/QTc. The Day 1 ECG measurement for Study BA058-05-005 will serve as the Visit 10 ECG measurement for Study BA058-05-003. An ECG will also be obtained atMonth 6. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 23 Radius Health, Inc. Confidential 7.1.7 Clinical Laboratory Evaluations Clinical laboratory evaluations will be performed by a central laboratory. Prior to starting the study, the Sponsor (or its designee) will provide each Investigatorwith copies of the appropriate laboratory certifications and normal ranges for all laboratory parameters to be performed by that laboratory. The blood and urinalysis samples are to be obtained under fasting conditions (NPO for 8 hours; water is acceptable) in the morning of each scheduled study visitson Day 1 and Months 6, 12, 18, and 24. All clinically significant laboratory abnormities indicating an adverse event will be followed up by repeat testing and further investigated as necessary, according tothe judgment of the Investigator. 7.1.8 Clinical Chemistry and Urinalysis (Dipstick) Clinical chemistry and dipstick urinalysis will be performed on Day 1 and at Months 6, 12, 18, and 24. Urinalysis will be performed using samples freshly voidedduring the clinic visit. If there are positive findings noted on the dipstick, a urine microscopic examination will be performed. The following tests will beperformed: Serum Chemistry·Sodium·Potassium·Chloride·Inorganic phosphorus·Albumin·Total protein·Glucose·Blood urea nitrogen (BUN)·Creatinine·Uric acid·Aspartate aminotransferase (AST)·Alanine aminotransferase (ALT)·Gamma-glutamyltranspeptidase (GGT)·Creatine phosphokinase (CPK)·Alkaline phosphatase·Total bilirubin·Lactate dehydrogenase (LDH)·Cholesterol·Triglycerides·Total calciumUrinalysis·pH·Glucose·Protein·Ketones·Bilirubin·Blood·Urobilinogen Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 24 Radius Health, Inc. Confidential ·Specific gravity·Nitrite·Leukocytes 7.1.9 Hematology Hematology testing will be performed on Day 1 and at Months 6, 12, 18, and 24. The following tests will be performed: Hematology :·Hemoglobin·Hematocrit·WBC count with differential in absolute counts·RBC count·Mean corpuscular volume (MCV)·Mean corpuscular hemoglobin concentration (MCHC)·Mean corpuscular hemoglobin (MCH)·Platelet count 7.1.10 Coagulation Coagulation testing will be performed on Day 1 and at Months 6 and 24. The following tests will be performed: ·Prothrombin time (PT)·Partial thromboplastin time (PTT) 7.1.11 24-Hour Urine Collection The 24-hour urine collection is to be begun the day before the Day 1 and Month 6 visits. If a sample was not able to be collected on the day prior to the Day 1 visit(i.e., if the subject had not yet signed the ICF for study participation), a 24-hour urine sample must be collected on the day prior to the Month 3 visit. Subjects are tobe instructed to begin the urine collection by discarding the first morning void (~6 a.m.) the day prior to the scheduled clinic visit and to then collect their urine for24 hours. A final void is to be collected at the end of the 24-hour period and the urine collection transported to the clinic by the subject. The 24-hour urinalysis willbe used to measure urinary calcium and urinary creatinine. 7.1.12 Bone Mineral Density All subjects will have bone mineral density measurements (BMD) taken via DXA at Months 6, 12, 18, and 24. The End-of-Treatment (Visit 9) bone mineraldensity tests for Study BA058-05-003 will serve as the baseline BMD measurements for Study BA058-05-005. DXAs will be performed on the hip (femoral neck) and spine (L1-4). The spinal DXA is to be taken in the postero-anterior (PA) projection with any subsequentspinal DXA to be taken in the same projection. Subjects who underwent wrist DXAs in Study BA058-05-003 will also have wrist DXAs performed at Months 6,12, 18, and 24. The same side of the hip and wrist that were used in Study BA058-05-003 must be used for the DXA scan, and the same scanner should be usedthroughout the study, when possible. If the independent radiologist identifies any patient who shows a continuing significant deterioration from the Day 1 assessment of Study BA058-05-005 (>7%) ofBMD at spine or hip during the study, the study physician will be notified, the assessment will be repeated Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 25 Radius Health, Inc. Confidential and, if confirmed, the patient will be discontinued from the study. The study physician will make this determination on the basis of the centrally read DXA relativeto the baseline measurement in consultation with the Sponsor Medical Monitor. 7.1.13 Serum Markers of Bone Metabolism Blood samples to measure bone markers will be taken on Day 1 and at Months 6, 12, 18 and 24. The results of the bone markers will be reported in the same subsetof subjects reported on for Study BA058-05-003. The following markers of bone formation will be measured: · Serum N-terminal propeptide of type I procollagen (PINP); · Serum bone-specific alkaline phosphatase (BSAP); · Serum osteocalcin. The following marker of bone resorption will be measured: · Serum C-telopeptides of type 1 collagen crosslinks (CTX). 7.1.14 Clinical and Radiologic Evaluation of Fractures Subjects will undergo protocol directed antero-posterior and lateral radiographs of the lumbar and thoracic spines at Month 6 and Month 24. The End-of-Treatment(Visit 9) clinical and radiological evaluation of fractures for Study BA058-05-003 will serve as the baseline assessments for Study BA058-05-005. Subjects willalso be clinically evaluated for non-vertebral fractures (wrist, hip, rib, etc.) that occur de novo during the Treatment Period. Documentation should be obtained onall de novo fractures that occur during the Treatment Period. This documentation should be maintained in the source documents. All radiographs will be viewed and assessed centrally by a blinded, independent assessor (radiologist) on the basis of existing baseline and study-acquired vertebraldeformity. Fractures will be assessed according to the severity scale of Genant (1993). A second blinded radiologist will confirm the assessment of the firstreviewer for all subject radiographs in which an incident fracture has been identified. In the case of any disagreement, a third consensus assessment will be made toadjudicate the incident fracture. Fractures identified during the study will not be recorded as AEs unless the subject is hospitalized, the fracture is complicated, or the Investigator considers thefracture to be unrelated to the subject’s underlying osteoporosis. All fractures (vertebral and non-vertebral) will be identified and evaluated as part of the diseaseassessment and will be documented in the fracture page of the case report form and source documents. 7.1.15 Abaloparatide Antibody Assessments The occurrence of anti-drug antibodies will be assessed at the completion of the initial six months of the study. Serum samples will be drawn at Month 6. Anysubject who tests positive, or has previously tested positive for antibodies will be retested at six month intervals until the antibody titer is negative. At thecompletion of the 24 months of the study, if the subject is still antibody positive, the subject will sign a new consent form to allow the antibody draws to continue.Exact procedures for collection, preparation, storage, and shipping of these samples will be detailed in a separate document. During the 24 months of the study, theactual time and date of each blood collection will be recorded on the Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 26 Radius Health, Inc. Confidential appropriate source document and in the eCRF. Information on antibodies collected subsequent to the 24 months of the present study will be collected in a paper orelectronic CRF. 7.1.16 Subject Diaries A weekly diary will be completed by the subject beginning on the Day 1 visit and continuing until the last day of Month 24. This diary will capture missed doses ofvitamin D, calcium and alendronate. The weekly diary will be reviewed at each study visit. 7.1.17 Activity and Diet Subjects who qualify for enrollment in the study will have no restrictions placed on their usual level of activity or on their usual diet, unless directed by the treatingphysician for medically justified reasons. 8.0  ADVERSE EVENTS AND SAFETY EVALUATION Timely, accurate, and complete reporting and analysis of safety information from clinical studies are crucial for the protection of subjects, Investigators and theSponsor, and is mandated by Regulatory Agencies worldwide. All clinical trials sponsored by RADIUS will be conducted in accordance with Standard OperatingProcedures (SOPs) that have been established to conform to regulatory requirements worldwide to ensure appropriate reporting of safety information. 8.1  Definitions, Documentation, and Reporting 8.1.1 Adverse Event Definition An adverse event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product, which does not necessarily have a causalrelationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporallyassociated with the use of the study drug, whether or not it is considered to be study drug related. This includes any newly occurring event or previous conditionthat has increased in severity or frequency since the administration of study drug. 8.1.2 Serious Adverse Event Definition A serious adverse event (SAE) is any adverse event, occurring at any dose and regardless of causality that: · Results in death. · Is life-threatening. Life-threatening means that the subject was at immediate risk of death from the reaction as it occurred, i.e., it does not include areaction which hypothetically might have caused death had it occurred in a more severe form. · Requires in-patient hospitalization or prolongation of existing hospitalization. Hospitalization admissions and/or surgical operations scheduled tooccur during the study period, but planned prior to study entry are not considered AEs if the illness or disease existed before the subject was enrolledin the trial. Provided that the illness/disease did not deteriorate in an unexpected manner during the trial (e.g., surgery performed earlier thanplanned). Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 27 Radius Health, Inc. Confidential · Results in persistent or significant disability/incapacity. Disability is defined as a substantial disruption of a person’s ability to conduct normal lifefunctions. · Is a congenital anomaly/birth defect. This includes any anomaly detected at or after birth, or any anomaly that results in fetal loss. · Is an important medical event. An important medical event is an event that may not result in death, be life-threatening, or require hospitalization, butmay be considered an SAE when, based upon appropriate medical judgment, it may jeopardize the subject and may require medical or surgicalintervention to prevent one of the outcomes listed in the definitions for SAEs. Examples of such medical events include allergic bronchospasmrequiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in in-patient hospitalization, or thedevelopment of drug dependency or drug abuse. Clarification should be made between the terms “serious” and “severe” since they are not synonymous. The term “severe” is often used to describe the intensity(synonym: severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor medicalsignificance (such as a severe headache). This is not the same as “serious,” which is based on subject/event outcome or action criteria described above and areusually associated with events that pose a threat to a subject’s life or functioning. A severe adverse event does not necessarily need to be considered serious. Forexample, persistent nausea of several hours duration may be considered severe nausea but not an SAE. On the other hand, a stroke resulting in only a minor degreeof disability may be considered mild, but would be defined as an SAE based on the above noted criteria. Seriousness (not severity) serves as a guide for definingregulatory reporting obligations. 8.2  Monitoring of Adverse Events and Period of Observation All AEs will be monitored until they are resolved or have become chronic or stable. AEs and SAEs will be recorded on the case report forms starting from the timeof subject entry from Day 1 of the study until the final study visit (Month 24). Any SAEs that occur at any time after completion of the study, which theInvestigator considers to be related to study drug, must be reported to the Sponsor or its designee. 8.3  Procedures for Recording and Reporting AEs and SAEs All adverse events spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physicalexamination or other diagnostic procedures must be recorded in the source document and on the appropriate page of the case report form. Any clinically relevantdeterioration in laboratory assessments or other clinical findings is considered an adverse event and must be recorded on the appropriate pages of the case reportform. When possible, signs and symptoms indicating a common underlying pathology should be noted as one comprehensive event. All SAEs that occur during the course of the study, as defined by the protocol, must be reported by the Investigator to the Study Safety Officer by completing andtransmitting the SAE Form within one working day from the point in time when the Investigator becomes aware of the SAE. In addition, all SAEs including alldeaths, which occur up to and including 30 days after administration of the last dose of study drug, must be reported to the Study Safety Officer within one workingday. All SAEs and deaths must be reported Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 28 Radius Health, Inc. Confidential whether or not considered causally related to the study drug. SAE forms will be provided to the study site. The information collected will include a minimum of thefollowing: Subject number, a narrative description of the event, and an assessment by the Investigator as to the intensity of the event, and relatedness to study drug.Follow-up information on the SAE may be requested by the CRO, the Study Safety Officer or the Sponsor Medical Monitor. Contact information for reportingSAEs to the Study Safety Officer is provided on the SAE form. It is the responsibility of the Investigator to promptly notify the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) of all serious adverse drugreactions involving risk to human subjects in accordance with the requirements of the IRB/IEC. An unexpected event is one that is not reported in the Investigator’sBrochure. Planned hospital admissions or surgical procedures for an illness or disease that existed before the subject was enrolled in the trial or before study drug was givenare not to be considered AEs unless they occur at a time other than the planned date. Fractures identified during the study are not to be recorded as AEs unless the subject is hospitalized, the fracture is complicated, or the Investigator considers thefracture to be unrelated to the subject’s underlying osteoporosis. All fractures will be identified and evaluated as part of the disease assessment and will bedocumented in the case report forms and source documents. For both serious and non-serious adverse events, the Investigator must determine the intensity of the event and the relationship of the event to study drugadministration. Intensity for each AE will be defined according to the following criteria: Intensity Definition Mild Awareness of sign or symptom, but easily tolerated. Moderate Discomfort enough to cause interference with normal daily activities. Severe Inability to perform normal daily activities If the intensity of an adverse event changes within a day, the maximum intensity should be recorded. If the intensity changes over a longer period of time, thechanges should be recorded as separate events (having separate onset and stop dates for each intensity). Relationship to study drug administration will be determined by the Investigator according to the following criteria: Relationship Definition None No relationship between the event and the administration of study drug. The event is related to other etiologies,such as concomitant medications or subject’s clinical state. Unlikely The current state of knowledge indicates that a relationship to study drug is unlikely or the temporal relationshipis such that study drug would not have had any reasonable association with the observed event. Possible A reaction that follows a plausible temporal sequence from administration of the study drug and follows a knownresponse pattern to the suspected study drug. The reaction might have Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 29 Radius Health, Inc. Confidential been produced by the subject’s clinical state or other modes of therapy administered to the subject. Probable A reaction that follows a plausible temporal sequence from administration of the study drug and follows a knownresponse pattern to the suspected study drug. The reaction cannot be reasonably explained by the knowncharacteristics of the subject’s clinical state or other modes of therapy administered to the subject. For the purpose of safety analyses, all AEs that are classified with a relationship to study medication administration of possible or probable will be consideredtreatment-related events. 8.4  Rules for Suspension of the Study As this is an extension study using approved alendronate products it is not anticipated that the study will need to be suspended, and therefore, suspension rules arenot assigned. In the event that the prior study (Study BA058-05-003) is suspended, the circumstances of the Study BA058-05-003 suspension will be considered todetermine if this study, Study BA058-05-005, should be suspended as well. 9.0  STATISTICAL PROCEDURES The primary objective of this study is to evaluate data obtained following six months of treatment with alendronate, in subjects who have previously received 18months of blinded treatment with Abaloparatide-SC/Placebo. Safety data will be obtained with clinical, laboratory and radiologic assessment. Following the initialsix months of treatment in this study, subjects will then enter the long-term observational phase of this study during which the subjects will continue to receivealendronate treatment for an additional 18 months. The specific objectives of this study are to: · Provide additional information on safety in study subjects receiving six months of treatment with alendronate following 18 months of treatment withAbaloparatide-SC/Placebo. · Provide information on the vertebral fracture rate of subjects receiving six months of treatment with alendronate following 18 months of treatment withAbaloparatide-SC/Placebo. · Provide additional information on non-vertebral fractures and BMD change associated with six months of treatment with alendronate following 18months of treatment with Abaloparatide-SC/Placebo. · Provide additional information on BMD change and osteoporosis status associated with 24 months of treatment with alendronate after 18 months oftreatment with Abaloparatide-SC/Placebo. The analysis performed at six months will be used as a follow-up to the 18 month fracture endpoint for Study BA058-05-003. Analyses will also be performedcumulatively at Month 12, 18, and 24 (i.e., Visits 4, 5, and 6). Full details of the statistical procedures to be used will be provided in the Statistical Analysis Plan. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 30 Radius Health, Inc. Confidential 9.1  Sample Size As this is an extension study, no formal sample size analysis was performed for this study. Study data will be tabulated and summarized. 9.2  Randomization, Stratification and Blinding Osteoporosis treatment will be open label and no randomization is required. 9.3  Populations for Analysis All analyses and data summaries will be presented for the Intent-to-Treat (ITT) or Safety Population. In addition key selected endpoints will also be analyzed forthe mITT and Per Protocol Populations. 9.3.1 ITT (Safety) Population The Safety Population is comprised of all patients who receive one or more doses of study medication. 9.3.2 Modified Intent-to-Treat Population The Modified ITT Population includes all patients with Pretreatment and at least one post-baseline evaluable radiologic assessments. 9.3.3 Per Protocol Population The Per-Protocol (PP) population includes subjects in the mITT population who complied with treatment and did not have any protocol violations. A protocol violation is defined as a deviation from basic requirements of the study protocol, including inclusion and exclusion criteria, concomitantmedication restrictions, or any other protocol requirements that result in a significant added risk to the study subject or has an impact on the quality of thedata collected or the outcome of the study. A protocol deviation is defined as a deviation from the protocol that does not impose added risk to the study design or the study subject. The criteria forthe determination of the evaluability of subjects will be defined in the Statistical Analysis Plan. 9.4  Procedures for Handling Missing, Unused, and Spurious Data All available data will be included in the data listings and tabulations. Where appropriate, imputations of values for missing data for primary and secondaryefficacy analyses will be performed as specified in the Statistical Analysis Plan. All data recorded on the CRF will be included in the data listings that willaccompany the clinical study report. 9.5  Statistical Methods 9.5.1 Statistical Considerations Statistical analysis will focus on safety, fracture incidence, including vertebral fracture and BMD change following six months of alendronate treatment in subjectswho have previously received 18 months of blinded treatment with Abaloparatide-SC/Placebo. Additional Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 31 Radius Health, Inc. Confidential analyses will also be cumulatively at Month 12, 18, and 24 (i.e., Visit 4, 5, and 6). Full details of these analyses will be provided in the Statistical Analysis Plan. The efficacy and safety analyses performed at six months will be used as a follow-up to the 18 month fracture endpoint for Study BA058-05-003. Subjects will beanalyzed based upon the randomization assignment in the BA058-05-003 study. 9.5.2 Baseline Comparisons Baseline characteristics, medical history, physical examination, vital signs and ECG, will be summarized using standard descriptive statistics. 9.5.3 Fractures and BMD Analysis All specified endpoints will be summarized by treatment group and study period using standard descriptive statistics (n, mean, SD, median, minimum, maximum,or n and %, as appropriate). The fracture incidence and BMD results from the additional six months of treatment with alendronate will be analyzed based on thetreatment arm they were randomized to in the BA058-05-003 study. These analyses will be conducted on all subjects with baseline and post-baseline data. Theanalysis performed at six months will be used a follow-up to the 18 month fracture endpoint for Study BA058-05-003. Vertebral fractures based on radiologic assessments will also be analyzed at Month 24. Additional analyses for the other endpoints will also be performedcumulatively at Month 12, 18, and 24 (i.e., Visits 4, 5, and 6). Full details of these analyses will be provided in the Statistical Analysis Plan. 9.5.4 Safety Analysis Data will be summarized and tabulated based on the enrolled population for this Extension Study. All subjects enrolled in the Extension Study will be included inthe safety analysis that will be performed on the following parameters: · Incidence and severity of AEs; · Pathological changes in hematology, chemistry and urinalysis data based on normal ranges supplied by the clinical laboratory, if applicable; Safety assessments for changes in physical examination, vital signs, ECG, and laboratory tests will be descriptively summarized by treatment and study periods.The results of anti-BA058 testing will be summarized. Concomitant medication classes will be categorized using World Health Organization (WHO) drugdictionary and summarized by number and percent of subjects using each class by treatment group. All treatment emergent adverse events (TEAEs) will be codedfor system organ class (SOC) and preferred term (PT) using MedDRA and the number (%) of subjects experiencing each AE (SOC/PT) will be summarized bytreatment, relationship to treatment, and severity. All serious adverse events (SAE) will be listed and the number (%) of subjects with an SAE presented bytreatment group. Similar safety analyses will be conducted cumulatively at Months 12, 18, and 24 (i.e., Visits 4, 5, and 6). Full details of these analyses will be provided in theStatistical Analysis Plan. 9.5.5 Procedures for Reporting Deviations to Original Statistical Analysis Plan All deviations from the original statistical analysis plan will be provided in the final clinical Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 32 Radius Health, Inc. Confidential study report. 9.6  Data Oversight 9.6.1 Central Review of Radiographs and DXA Scans All radiographs will be viewed and assessed by a blinded, independent assessor (radiologist) on the basis of existing baseline and study-acquired vertebraldeformity, and fractures will be assessed according to the method of Genant. A second blinded radiologist will review the assessment of the first reviewer for allsubject radiographs in which an incident fracture has been identified. In the case of any disagreement, a third consensus assessment will be made to adjudicate theincident fracture. All study DXA scans will also be evaluated centrally by a blinded independent reviewer. The primary objective of the independent review is toprovide objective data to determine the treatment benefit as demonstrated on the pertinent radiologic and clinical data associated with this study. 10.0  ADMINISTRATIVE REQUIREMENTS 10.1  Good Clinical Practice This study will be conducted in accordance with the International Conference on Harmonization (ICH) for Good Clinical Practice (GCP) and the appropriateregulatory requirements. The Investigator will be thoroughly familiar with the appropriate use of the study medication as described in the protocol and theInvestigator’s Brochure. Essential clinical documents will be maintained to demonstrate the validity of the study and the integrity of the data collected. TheInvestigator/institution should establish master files at the beginning of the study which will be maintained and updated during the study and retained thereafteraccording to the appropriate regulations. 10.2  Ethical Considerations The study will be conducted in accordance with ethical principles founded in the Declaration of Helsinki. The Institutional Review Board (IRB)/Independent EthicsCommittee (IEC) will review all appropriate study documentation in order to safeguard the rights, safety and well-being of the subjects. The study can only beconducted at study sites where IRB/IEC approval has been obtained. The protocol, informed consent form, Investigator’s Brochure, advertisements (if applicable),and all other forms of information given to subjects will be provided to the IRB/IEC by the Investigator. In addition, reports on the progress of the study will besubmitted to the IRB/IEC by the Investigator at the appropriate intervals. 10.3  Subject Information and Informed Consent Each subject (or a legally authorized representative) must give written informed consent prior to any new study-specific procedures being conducted. It is theresponsibility of the Investigator to ensure written informed consent is obtained from each subject participating in this study after an explanation of the objectives,methods, discomforts and potential risks of the study has been provided. The Investigator (or study personnel) must also explain to each subject that he/she is freeto refuse participation in the study or to withdraw from it at any time. Each subject will also be told that his/her records may be examined by competent authoritiesand authorized persons but that personal information will be treated as strictly confidential and will not be publicly available. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 33 Radius Health, Inc. Confidential The informed consent form must be in accordance with the Declaration of Helsinki, ICH and GCP guidelines, and be approved by the Sponsor and the IRB/IEC.State or local laws may require additional information. Each subject (or his/her legally authorized representative) must sign and be given a copy of the informedconsent form. Each subject’s signed informed consent form must be maintained by the Investigator and be readily available for review by the Sponsor (or itsdesignee) or the Regulatory Authorities. 10.4  Protocol Compliance The Investigator will conduct this study in compliance with the protocol provided by the Sponsor and given approval/favorable opinion by the IRB/IEC and theappropriate Regulatory Authority(ies). Changes to the protocol will not be made without agreement of the Sponsor Medical Monitor. All changes to the protocolwill require IRB/IEC approval prior to implementation, except when necessary to eliminate an immediate hazard to study subjects or when the change involvesonly logistical or administrative aspects of the study (e.g., change in Sponsor Medical Monitor or telephone number). The IRB/IEC may provide, if applicableregulations permit, expedited review and approval/favorable opinion for minor changes in ongoing studies. The Sponsor will submit all protocol changes to theappropriate Regulatory Authority in accordance with the governing regulations. In situations requiring a departure from the protocol, the Investigator or other physician in attendance will contact the Sponsor Medical Monitor by telephone, e-mail or fax. If possible, this contact will be made before implementing any departure from the protocol. In all cases, contact with the Sponsor Medical Monitormust be made as soon as possible in order to review the situation and agree on an appropriate course of action. The case report form and source document willdescribe any departure from the protocol and the circumstances requiring it. 10.5  Case Report Form Completion eCRFs will be developed to collect information obtained during this study. It is the Investigator’s responsibility to ensure that the e-CRFs are completed for eachsubject enrolled in this study and for the accuracy, completeness, legibility and timeliness of the data reported in each e-CRF. Data for subjects who are screenedbut not enrolled into the study because they do not meet study criteria or do not complete all screening procedures, should be recorded in the e-CRF. eCRFs will be completed and any corrections of data will be made according to procedures provided by the Sponsor (or designee). 10.6  Source Documents Source documents are defined as original documents, data and records. This may include hospital records, clinical and office charts, laboratory data/information,work sheets, subjects’ diaries or evaluation checklists, pharmacy dispensing and other records, recorded data from automated instruments, microfiches,photographic negatives, microfilm or magnetic media, ECG printouts, and/or x-rays. The Investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspection(s), providing direct access to source datadocuments. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 34 Radius Health, Inc. Confidential 10.7  Study Monitoring The Sponsor (or its designee) will ensure that the study is monitored in accordance with ICH-GCP Guidelines. Monitoring is the act of overseeing the progress of aclinical trial and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures, Good Clinical Practice, andthe applicable regulatory requirements and that the study data are accurate, complete and verifiable from source data. All study documentation and other sourcedata will be made available to the Sponsor (or its designee), the IRB and to Regulatory Authorities for inspection upon request. 10.8  On-Site Audits Representatives of the IRB or the Sponsor (or designee) may visit the study site to carry out an audit of the study in compliance with regulatory guidelines andcompany policy. Such audits will require access to all study records including source documents, CRFs, and other study documents. Direct access to these studyrecords must be guaranteed by the Investigator, who must provide support for these activities at all times. Similar auditing procedures may also be conducted by agents of any Regulatory Authority reviewing the results of this study. The Investigator/institution shouldimmediately notify the Sponsor if they have been contacted by a Regulatory Authority concerning an upcoming inspection. 10.9  Drug Accountability Accountability for the study medication at the study site is the responsibility of the Investigator. Drug accountability will be performed only on alendronate,calcium and vitamin D. The Investigator will ensure that the study medication is used only in accordance with this protocol. Where allowed, the Investigator maychoose to assign some of the study medication accountability responsibilities to qualified study personnel. Study medication accountability records indicating the delivery date to the study site, inventory at the study site and dispensing/use will be maintained. Theserecords will adequately document that the study medications were dispensed and returned as specified in the protocol. Accountability records will include dates,quantities, and subject numbers. The Sponsor (or its designee) will review study medication accountability records at the study site on an ongoing basis during thestudy. All used and unused study medication must be inventoried, accounted for, and approved by the Sponsor (or its designee) prior to destruction. If the site is notcapable of study drug disposal/destruction, the Sponsor will arrange for an alternative method. Records of disposal must be maintained with the study records. 10.10  Record Retention The Investigator will maintain all study records according to ICH/GCP and applicable regulatory requirements. Essential documents must be retained for two yearsafter the final marketing approval in an ICH region or at least two years have elapsed since the discontinuation of clinical development of the study medication. It isthe responsibility of the Sponsor to inform the Investigator of when these documents can be destroyed. In addition, all subject medical records and other sourcedocumentation will be kept for the maximum time permitted by the hospital, institution or medical practice. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 35 Radius Health, Inc. Confidential The Investigator/institution will take measures to prevent accidental or premature destruction of these documents. If the responsible Investigator retires, relocates,or for other reasons withdraws from the responsibility of keeping the study records, custody must be transferred to a person who will accept the responsibility. TheSponsor must be notified in writing of the name and address of the new custodian. 10.11  Study Termination This study may be terminated at any time by the Sponsor if there is sufficient reasonable cause. Circumstances that may warrant termination include, but are notlimited to: · Determination of unexpected, significant, or unacceptable risk to subjects. · Failure of enrollment · Administrative reasons · Plans to modify, suspend or discontinue the development of the study drug. In addition, individual study sites may be terminated from study participation for reasons including, but not limited to the following: · Failure to enter subjects at an acceptable rate. · Insufficient adherence to protocol requirements. · Incomplete and/or non-evaluable data. In all cases, the terminating parties will provide written notification documenting the reason for study termination to all the relevant parties. Should the study or an individual site be prematurely closed, all study materials (completed, partially completed, and blank CRFs, study drug, etc.) must bereturned to the Sponsor (or its designee). 10.12  Liability and Insurance The Sponsor has subscribed to an insurance policy covering, in its terms and provisions, its legal liability for injuries caused to participating persons and arising outof this research performed strictly in accordance with the scientific protocol as well as with applicable law and professional standards. 11.0  USE OF INFORMATION AND PUBLICATION OF STUDY FINDINGS 11.1  Use of Information All information regarding BA058 supplied by the Sponsor (or its designee) to the Investigator is privileged and confidential information. The Investigator agrees touse this information to accomplish the study and will not use it for other purposes without prior consent from the Sponsor. The information developed during the conduct of this clinical study is also considered confidential and will be used by the Sponsor in connection with thedevelopment of BA058. This information may be disclosed as deemed necessary by the Sponsor to other clinical Investigators, other pharmaceutical companies,and to Regulatory Authorities. To allow for the use of the information derived from this study and to ensure complete and thorough Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 36 Radius Health, Inc. Confidential analysis, the Investigator is obligated to provide the Sponsor (or its designee) with complete study results and all data developed in this study and to allow directaccess to source data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory inspection. 11.2  Publication Results of this study may not be published prior to the completion of this study and completion of the formal clinical study report and other required regulatoryreports and documents. It is anticipated that the results of this study will be presented at scientific meetings and/or published in a peer reviewed scientific or medical journal. APublications Committee composed of Investigators participating in the study and representatives from the Sponsor as appropriate will be formed to oversee thepublication of the study results, which will reflect the experience of all participating study centers. Subsequently, individual Investigators may publish results from the study in compliance with their agreement with the Sponsor. A pre-publication manuscript mustbe provided to the Sponsor at least 30 days prior to the submission of the manuscript to a publisher. Similarly, the Sponsor will provide any company preparedmanuscript to the Investigators for review at least 30 days prior to submission to a publisher. The Investigator shall comply with the policy of the Sponsor regarding confidential or proprietary information in any such paper and agrees to withhold publicationof same for an additional 60 days in order to permit the Sponsor to obtain patent or other proprietary rights protection, if the Sponsor deems it necessary. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 37 Radius Health, Inc. Confidential 12.0  INVESTIGATOR AGREEMENT To be completed by the Investigator I have read Protocol BA058-05-005: “An Extension Study to Evaluate 24 Months of Standard-of-Care Osteoporosis Management Following Completion of 18Months of BA058 or Placebo Treatment in Protocol BA058-05-003”. I agree to conduct the study as detailed herein and in compliance with ICH Guidelines for Good Clinical Practice and applicable regulatory requirements and toinform all who assist me in the conduct of this study of their responsibilities and obligations. The signature below constitutes my agreement to the contents of this protocol. Signature of Principal Investigator Date Principal Investigator (print) Signature of Sponsor’s Medical Officer (where applicable) /s/ Lorraine Fitzpatrick 24 Aug 15Lorraine Fitzpatrick, MD Date Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 38 Radius Health, Inc. Confidential 13.0  REFERENCES Balena R, Toolan BC, Shea M, Markatos A, Myers ER, Lee SC, Opas EE, Seedor JG, Klein H, Frankenfield D, Quartuccio H, Fiovanti C, Clair J, Brown E, HayesWC, Rodan GA. The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength inovariectomized nonhuman primates. J Clin Invest 1993; 92:2577-2586. Balena R, Markatos A, Seedor JG, Gentile M, Stark C, Peter CP, Rodan GA. Long-term safety of the aminobisphosphonate alendronate in adult dogs. IIHistomorphometric analysis of the L5 vertebrae. J Pharmacol Exp Ther 1996; 276(1):277-83. Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, Lang TF, McGowan JA, Rosen CJ. One year of alendronate after one year of parathyroidhormone (1-84) for osteoporosis. N Engl J Med 2005; 353(6):555-565. Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonito RP, Rodriguez-Portales JA, Downs RW, Grupta J, Santora AC, Liberman UA, AlendronatePhase III Osteoporosis Treatment Study Group. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Eng J Med 2004 ;350(12):1189-99. Devogelaer JP, Broll H, Correa-Rotter R, Coming DC, De Deuxchaisnes CN, Geusens P, Hosking D, Jaeger P, Kaufman JM, Leite M, Leon J, Liberman U,Menkes CJ, Meunier PJ, Reid I, Rodriguez J, Romanowicz A, Seeman E, Vermeulen A, Hirsch LJ, Lombardi A, Plezia K, Santora AC, Yates AJ, Yuan W. Oralalendronate induces progressive increases in bone mass of the spine, hip and total body over 3 years in postmenopausal women with osteoporosis. Bone 1996;18(2):141-50. EMEA. Guideline on the evaluation of medicinal products in the treatment of primary osteoporosis. 2007. FDA. Guidelines for preclinical and clinical evaluation of agents used in the prevention or treatment of postmenopausal osteoporosis. 1994. FDA. Draft guidance: Development of parathyroid hormone for the prevention and treatment of osteoporosis. 2000. Fosamax® Prescribing Information. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2012. Genant HK, Wu CY, van KC, and Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 1993; 8:1137-1148. Guidance for Industry. E6 Good Clinical Practice: Consolidated Guidance. U.S.Department of Health and Human Services, Food and Drug Administration.April 1996. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 39 Radius Health, Inc. Confidential Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int 1997; 7:407-413. Lefage M-H, Balena R, Battle MA, Shea M, Seedor JG, Klein H, Hayes WC, Rodan GA. Comparison of alendronate and sodium fluoride effects on cencellous andcortical bone in minipigs. J Clin Invest 1995; 95:2127-2133. Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs Jr. RW, Dequeker J, Favus M, Seeman E, Recker RR, Capizzi T,Santora AC, Lombardi A, Shah RV, Hirsch LJ, Karpe DB. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausalosteoporosis. N Engl J Med 1995; 333(22):1437-43. Reginster JY, Burlet N. Osteoporosis: still increasing prevalence. Bone 2006; 38(Suppl 1):S4-9. Rittmaster RS, Bolognese M, Ettinger MP, Hanley DA, Hodsman AB, Kendler DL, Rosen CJ. Enhancement of bone mass in osteoporotic women with parathyroidhormone followed by alendronate. J Clin Endocrinol Metab 2000; 85(6):2129-34. Rizzoli R, Bonjour JP, and Ferrari SL. Osteoporosis, genetics and hormones. J Mol Endocrinol 2001; 26:79-94. Tucci JR, Tonino RP, Emkey RD, Peverly CA, Kher U, Santora AC 2 . Effect of three years of oral alendroneate treatment in postmenopausal women withosteoporosis. Am J Med 1996; 101(5):488-501. WHO Scientific Group on the assessment of osteoporosis at primary health care level. World Health Organization Summary Meeting Report 2007. World Medical Association Declaration of Helsinki. The World Medical Association, Inc. 2008. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 40nd  Radius Health, Inc. Confidential 14.0        APPENDICES Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 41 Radius Health, Inc. Confidential 14.1  Schedule of Visits and Procedures  1           Visit Visit 10 003/ 2 3 4 5 6 Study Day/Month: Visit 1(1) 005 Month 3 Month 6 Month 12 Month 18 Month 24 Day 1 90 180 360 540 720 Visit Window (Days) N/A ± 5 ± 14 ± 14 ± 14 ± 14 Procedure Informed consent X Review of entrance criteria X Recent health status X X X X X X Vital signs, weight and height measurements(2) X X X X X X Electrocardiogram X X Urinalysis (dipstick) (3) X X X X X Chemistry blood collection(4) X X X X X Hematology blood collection(5) X X X X X Coagulation blood collection(5) X X X PTH(1-84) X 25-hydroxy vitamin D level X 1,25-dihydroxy vitamin D level X Serum markers of bone metabolism(5) X X X X X BA058 antibody levels(6) X 24-hour urine collection (for calcium: creatinine and creatinineclearance)(7) X X(8)X Clinical and radiologic (spine, lumbar and thoracic vertebrae)fracture assessments X X Clinical assessment of de novo fractures(9) X X Bone mineral density of hip and spine by DXA(10) X X X X Bone mineral density of wrist by DXA(11) X X X X Calcium and vitamin D supplements Daily Alendronate administration (if applicable) Dosing as per prescribing information Study medication resupply (if applicable) X X X X Subject diary review(12) X X X X X Document adverse events and concomitant medications Daily Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 42 Radius Health, Inc. Confidential (1) The procedures for the Follow-up visit (Visit 10) for Study BA058-05-003 will serve as the procedures performed at Day 1 (for Study BA058-05-005). Theconsent form will need to be signed if it was not signed during the End-of-Treatment Visit (Visit 9) of Study BA058-05-003.(2) Vital signs (blood pressure, pulse rate, body temperature, and respiration rate) are to be recorded at each study visit. Only the blood pressure assessment on Day1 (Visit 10) needs to be orthostatic. Height is to be measured at each visit in the standing position using a medical stadiometer. Weight is to be measured at eachvisit. Orthostatic blood pressure is to be measured initially after 5 minutes in the supine position and then again after standing for three minutes.(3) All routine urinalysis will be performed on a sample freshly voided during the clinic visit.(4) These blood samples are to be obtained under fasting conditions (N.P.O. for 8 hours; water is acceptable) in the morning of each scheduled study visit.(5) Includes blood samples for PINP, bone-specific alkaline phosphatase, serum osteocalcin and CTX.(6) Subjects who remain positive at the 6 month antibody draw will have samples drawn for antibodies every six months until the antibody titer is negative.(7) Twenty-four hour urine collection will be used for urinary calcium and urinary creatinine measurements. Subjects will discard the 1 void and begin a 24-hoururine collection the day prior to the clinic visit.(8) A 24-hour urine collection will be collected at Month 3 only if a sample was not collected for the Day 1 (Visit 10).(9) Documentation should be obtained on all de novo fractures that occur during the Treatment Period. This documentation should be maintained in the sourcedocuments.(10) Each DXA for a given subject should be performed on the same machine, and if available, preferably by the same technician(11) Each DXA for a given subject should be performed on the same machine, and if available, preferably by the same technician. Only subjects who had wristst DXA assessments in Study BA058-05-003 will have wrist DXAs performed.(12) The subjects will maintain a diary throughout the study to record missed doses of medication (including supplements) on a weekly basis; the diaries are to bereviewed with the subject at each study visit. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 43 Radius Health, Inc. Confidential 14.2  Suggested Schedule of Events and Procedures by Study Visit The purpose of this guide is to provide more detailed instructions for the study procedures listed in Appendix 14.1. This guide presents the procedures in asuggested sequence of performance at each study visit. Further information may be found within the protocol and in other study reference manuals (e.g., ECG,clinical laboratory sample processing). Of note: · Blood and urinalysis samples are to be obtained under fasting conditions (NPO. for 8 hours; water is acceptable) in the morning of Day 1 and Months 6,12, 18, and 24. · DXA Scans: Always use the same study-validated machine; preferably the same technician. · The 24-hour urine collection will be started at home the day before the clinic visit where the collection is required. Subjects will be instructed to discardthe first morning void and begin the collection at least 24 hours before their clinic visit the following day. They will collect all urine for 24 hours with afinal void before coming to the clinic. Routine urinalyses are to be performed using samples freshly voided during the clinic visit. Subjects should receivea reminder to initiate their 24-hour urine 2 days before their scheduled visit. · Alendronate for Europe, Hong Kong and the US will be sourced centrally; alendronate for South America will be sourced locally by the medical centerand reimbursed by the Sponsor. · Subjects will be instructed to take the calcium and vitamin D supplements daily (in the evening with or without food or as otherwise instructed by theInvestigator) until discharge from the study. This is required until the end of Month 24. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 44 Radius Health, Inc. Confidential Definitions of Common Procedures: The terms used in the by-visit schedule that follows are further defined below. Recent health status (document any changes from last visit)· Question subject regarding any new health issues· Question subject regarding any new adverse events· Question subject regarding any new concomitant medications· Question subject regarding any new issues related to ability to continue with studyPulse, respiration and temperature:· Pulse rate (beats/minute) taken after approximately five minutes in the supine position.· Respiration rate (breaths/minute).· Body temperature (°C).Weight and height measurements:· Weight (kg).· Height (cm) standing measurements are to be performed using the same medical stadiometer and standardized procedures each time.Orthostatic blood pressure:· Orthostatic blood pressure (mmHg) (measured in same arm each time/each visit) is measured after five minutes in the supine position followed by ameasurement taken after 3 minutes in the standing position. Only the blood pressure assessment on Day 1 (Visit 10) needs to be orthostatic.ECG· Twelve-lead supine electrocardiogram· Print hard copy for reading by qualified study personnel· More than one ECG may be performed per time-point.24 hour urine collection· Subject to discard first morning void (suggest 6 a.m.) on day before clinic visit· Subject to collect urine for approximately 24 hours· Subject to collect final void at end of collection and bring collection to clinic.· Process for calcium and creatinineUrinalysis· Obtain under fasting conditions (NPO. except water for 8 hours)· Routine urinalysis is to be performed using a sample freshly voided during the clinic visit (microscopic examination if positive dipstick).Review study medication administration procedures with subject· Alendronate should be taken daily, preferably at the same time each morning/day of the weekScheduling and instructions for next clinic visit· Schedule visit· Remind subject of any fasting requirements· Provide urine collection instructions and materials as necessary· Remind subjects to complete the diaries until the end of the studyVitamin D and calcium supplements· Vitamin D and calcium supplements are required throughout the study. Only those supplements supplied as part of study medication may be used and areto be used at the daily recommended dose (see Section 5.1.2) .· Supplements should be taken in the evening, with or without food as instructed by the Investigator.· At each study visit, assess the subject’s supply and resupply as necessary.· Drug usage reconciliation is to be performed when a new supply is provided. Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 45 Radius Health, Inc. Confidential Visit 10 for Study BA058-05-003Day 1 Visit for Study BA058-05-005Day 1 VISIT ACTIVITIESDay 1 Day 1 Visit for Study BA058- 05-005 Visit 10 for Study BA058- 05-003 Written informed consent must be obtainedRecent health status· Document any changes since End-of-Treatment visit (Visit 9) from Study BA058- 05-003 Study staff will receive your prior days 24-hour urine sample (if a 24-hour urine sample was not collected prior to Day 1, the subjectmust begin a 24-hour urine sample on the day prior to the Month 3 visitSubject diary review· Review study medication diary (calcium and vitamin D)/dispense new diary if necessary· Record deviations in dosing or any AEs in source documents and CRFs· Collect diaries and enter data into CRF Vital signs, weight and height measurementOrthostatic blood pressureECGBlood collection: fasting conditions (NPO except water for 8 hours)· Chemistry· Hematology· Coagulation (PT and PTT)· Serum markers of bone metabolism, where applicable· PINP· bone-specific alkaline phosphatase· serum osteocalcin· serum CTX· Urinalysis (Dipstick) Study medication· Dispense three month supply of alendronate· Assess subject’s supply of calcium and vitamin D supplements; resupply as necessary· Instruct subject to take daily until they are discharged from the study Scheduling and instructions for next clinic visit· Remind subject to take study medication as instructed· 24-hour urine collection: If subjects did not provide a 24-hour urine sample for Visit 1, dispense urine collection container andinstruct subjects to perform 24- hour urine collection beginning the morning 24 hours prior to their next scheduled visit (Month3)· Remind subject to record study medication use Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 46 Radius Health, Inc. Confidential Month 3 Visit for Study BA058-05-005Day 90 (±5 days) VISIT ActivitiesMonth 3 Recent health status· Document any changes since previous visit Study staff will receive the prior days 24 hour urine sample, if applicableVital signs, height and weight measurementSubject diary review· Review study medication diary/dispense new diary if necessary· Record deviations in dosing or any AEs in source documents and CRFs.· Collect diaries and enter data into CRF Study medication· Dispense three month supply of alendronate· Assess subject’s supply of calcium and vitamin D supplements; resupply as necessary, instruct subject to take daily until theyare discharged from the study Scheduling and instructions for next clinic visit· 24-hour urine collection: Dispense urine collection container and instruct subjects to perform 24-hour urine collectionbeginning the morning 24 hours prior to their next scheduled visit (Month 6)· Remind subject to take study medication as instructed· Remind subject to record study medication use Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 47 Radius Health, Inc. Confidential Month 6 Visit for Study BA058-05-005Day 180 (±14 Days) VISIT ActivitiesMonth 6 Physical ExaminationRecent Health Status· Document any changes from last visitCollect 24 hour urine sample from subjectStudy staff will receive your prior days 24-hour urine sample· Review diary of study medication· Collect diary and enter data into CRF, record dosing deviations or any AEs in source documents and CRFsVital signs, weight and height measurementECGBlood collection: fasting conditions (NPO except water for 8 hours)· Chemistry· Hematology· Coagulation (PT and PTT)· Serum markers of bone metabolism, where applicable· PINP· bone-specific alkaline phosphatase· serum osteocalcin· serum CTX· BA058 antibody levels· Urinalysis (Dipstick)Clinical and radiologic fracture evaluations· Obtain antero-posterior and lateral radiographs of the lumbar and thoracic vertebrae· Document any non-vertebral fracturesBone mineral density· Perform DXA of spine (L1-L4), hip (femoral neck), and wrist (distal 1/3 radius), where applicable.Study Medication· Dispense six month supply of alendronate· Assess subject’s supply of calcium and vitamin D supplements, resupply as necessary Scheduling and instructions for next clinic visit· Remind subject to take study medication as instructed· Remind subject to record study medication use Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 48 Radius Health, Inc. Confidential Month 12 Visit for Study BA058-05-005Day 360 (±5 days) VISIT ActivitiesMonth 12 Recent health status· Document any changes since previous visit Vital signs, height and weight measurementBlood collection: fasting conditions (NPO except water for 8 hours)· Chemistry· Hematology· Serum markers of bone metabolism, where applicable· PINP· bone-specific alkaline phosphatase· serum osteocalcin· serum CTX· Urinalysis (Dipstick)Bone mineral density· Perform DXA of spine (L1-L4), hip (femoral neck), and wrist (distal 1/3 radius), where applicable. Clinical fracture assessment: Subject diary review· Review study medication diary/dispense new diary if necessary· Record deviations in dosing or any AEs in source documents and CRFs.· Collect diaries and enter data into CRF Study medication· Dispense six month supply of alendronate· Assess subject’s supply of calcium and vitamin D supplements; resupply as necessary, instruct subject to take daily until theyare discharged from the study Scheduling and instructions for next clinic visit· Remind subject to take study medication as instructed· Remind subject to record study medication use Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 49 Radius Health, Inc. Confidential Month 18 Visit for Study BA058-05-005Day 540 (±5 days) VISIT ActivitiesMonth 18 Recent health status· Document any changes since previous visit Vital signs, height and weight measurementBlood collection: fasting conditions (NPO except water for 8 hours)· Chemistry· Hematology· Serum markers of bone metabolism, where applicable· PINP· bone-specific alkaline phosphatase· serum osteocalcin· serum CTX· Urinalysis (Dipstick)Bone mineral density· Perform DXA of spine (L1-L4), hip (femoral neck), and wrist (distal 1/3 radius), where applicable. Clinical fracture assessment: Subject diary review· Review study medication diary/dispense new diary if necessary· Record deviations in dosing or any AEs in source documents and CRFs.· Collect diaries and enter data into CRF Study medication· Dispense six month supply of alendronate· Assess subject’s supply of calcium and vitamin D supplements; resupply as necessary, instruct subject to take daily until theyare discharged from the study Scheduling and instructions for next clinic visit· Remind subject to take study medication as instructed· Remind subject to record study medication use Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 50 Radius Health, Inc. Confidential Month 24 Visit for Study BA058-05-005Day 720 (±5 days) VISIT ActivitiesMonth 24 Recent health status· Document any changes since previous visit Vital signs, height and weight measurementSubject diary review· Review study medication diary· Record deviations in dosing or any AEs in source documents and CRFs.· Collect diaries and enter data into CRFBlood collection: fasting conditions (NPO except water for 8 hours)· Chemistry· Hematology· Coagulation (PT and PTT)· Serum markers of bone metabolism, where applicable· PINP· bone-specific alkaline phosphatase· serum osteocalcin· serum CTX· Urinalysis (Dipstick) Clinical and radiologic fracture evaluations· Obtain antero-posterior and lateral radiographs of the lumbar and thoracic vertebrae· Document any non-vertebral fractures Bone mineral density· Perform DXA of spine (L1-L4), hip (femoral neck), and wrist (distal 1/3 radius), where applicable. Study medication· Collect unused study medication Discharge subject from study· Subject is terminated from the study unless adverse events require further follow through Discuss continuing treatment options· Subjects will receive standard-of-care management according to their physician Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 51 Radius Health, Inc. Confidential 14.3  Eastern Cooperative Oncology Group (ECOG) Common Toxicity Criteria Category Toxicity (units) Grade 0 Grade 1 Grade 2 Grade 3 Grade 4Haematology WBC (x10 /L) 4 3.0 - 3.9 2.0 - 2.9 1.0 - 1.9 < 1.0Platelets (x10 /L) WNL 75.0 - normal 50.0 - 74.9 25.0 - 49.9 < 25.0Haemoglobin (g/L); (mmol/L) WNL 100.0 – normal; 6.2 - normal 80.0 - 99.0; 5.0 – 6.1 65.0 - 79.0 4.0 – 4.9 < 65.0 < 4.0Granulocytes/ Bands (x10 /L) 2 1.5 - 1.9 1.0 - 1.4 0.5 - 0.9 < 0.5Lymphocytes (x10 /L) 2 1.5 - 1.9 1.0 - 1.4 0.5 - 0.9 < 0.5Haemorrhage none mild, no transfusion gross,1 - 2 unitstransfusion per episode gross, 3 - 4 unitstransfusion perepisode massive, > 4 unitstransfusion perepisodeCoagulation Fibrinogen WNL 0.99 - 0.75 x N 0.74 - 0.50 x N 0.49 - 0.25 x N < 0.25 x NProthrombin time(quick) WNL 1.01 - 1.25 x N 1.26 - 1.50 x N 1.51 - 2.00 x N > 2.00 x NPartial thromboplastin time WNL 1.01 - 1.66 x N 1.67 - 2.33 x N 2.34 - 3.00 x N > 3.00 x NMetabolic 9 9 9 9 Hyperglycaemia (mmol/L) < 6.4 6.4 – 8.9 9.0 – 13.9 14.0 – 27.8 > 27.8 orketoacidosisHypoglycaemia (mmol/L) > 3.6 3.6 – 3.1 3.0 – 2.3 2.2 – 1.7 < 1.7Amylase WNL < 1.5 x N 1.5 - 2.0 x N 2.1 - 5.0 N > 5.0 x NHypercalcaemia (mmol/L) < 2.65 2.65 - 2.88 2.89 - 3.13 3.14 - 3.36 > 3.37Hypocalcaemia (mmol/L) > 2.10 2.10 - 1.94 1.93 - 1.74 1.73 - 1.52 < 1.51Hypomagnesaemia (mmol/L) > 0.58 0.58 - 0.48 0.47 - 0.36 0.35 - 0.24 < 0.23Gastrointestinal Nausea none able to eat reasonableintake intake significantlydecreased but can eat no significantintake —Vomiting none 1 episode in 24 hrs 2 - 5 episodes in 24 hrs 6 - 10 episodes in24 hrs > 10 episodes in 24hrs or requiringparenteral supportDiarrhoea none increase of 2 - 3stools/day over pre-Rx increase of 4 – 6stools/day, or nocturnalstools, or moderatecramping increase of 7 - 9stools/day, orincontinence, orsevere cramping increase of > 10stools/day orgrossly bloodydiarrhoea, or needfor parenteralsupportStomatitis none painless ulcers,erythema, or mildsoreness painful erythema,oedema, or ulcers butcan eat solids painful erythema,oedema, or ulcersand cannot eatsolids requires parenteralor enteral supportfor alimentationLiver Bilirubin (N = 17 µmol/L) WNL — < 1.5 x N 1.5 - 3.0 x N > 3.0 x N Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 52 Radius Health, Inc. Confidential Category Toxicity (units) Grade 0 Grade 1 Grade 2 Grade 3 Grade 4Transaminase (SGOT, SGPT) WNL 2.5 x N 2.6 - 5.0 x N 5.1 - 20.0 x N > 20.0 x NAlkaline phosphatase or 5-nucleotidase WNL < 2.5 x N 2.6 - 5.0 x N 5.1 - 20.0 x N > 20.0 x NLiver- clinical No change frombaseline — — precoma hepatic comaKidney, bladder Creatinine WNL < 1.5 x N 1.5 - 3.0 x N 3.1 - 6.0 x N > 6.0 x NProteinuria No change 1 (+) or < 0.3 g% or 3g/L 2 - 3 (+) or 0.3-1.0 g%or 3-10 g/L 4 (+) or > 1.0 g%or > 10g/L nephroticsyndromeHaematuria Negative microscopic only gross, no clots no Rxneeded gross and clotsbladder irrigation requirestransfusion orcystectomyWeight gain/ loss < 5.0% 5.0 - 9.9% 10.0 - 19.9% 20.00% —Pulmonary Pulmonary none or nochange asymptomatic, withabnormality in PFTs dyspnoea on significantexertion dyspnoea atnormal level ofactivity dyspnoea at restCardiac Cardiac arrhythmias none asymptomatic, transient,requiring no therapy recurrent or persistent,no therapy required requirestreatment requiresmonitoring; orhypotension, orventriculartachycardia orfibrillationCardiac function none asymptomatic, declineof resting ejectionfraction by less than 20% of baseline value asymptomatic, declineof resting ejectionfraction by more than20% of baseline value mild CHF,responsive totherapy severe orrefractory CHFCardiac ischaemia none non-specific T- waveflattening asymptomatic, ST and Twave changessuggesting ischaemia angina withoutevidence ofinfraction acute myocardialinfarctionCardiac- pericardial none asymptomatic effusion,no intervention required pericarditis (rub, chestpain, ECG changes) symptomaticeffusion;drainage required tamponade;drainage urgentlyrequiredHypertension none or nochange asymptomatic, transientincrease by greater than20 mmHg (D) or to >150/100 if previouslyWNL. No treatmentrequired. recurrent or persistentincrease by greater than20 mmHG (D) or to >150/100 if previouslyWNL. No treatmentrequired. requires therapy hypertensivecrisisHypotension none or nochange changes requiring notherapy (includingtransient orthostatichypotension) requires fluidreplacement or othertherapy but nothospitalisation requires therapyandhospitalisation;resolves within48 hrs ofstopping theagent requires therapyandhospitalisationfor > 48 hrs afterstopping theagent Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 53 Radius Health, Inc. Confidential Category          Toxicity (units) Grade 0 Grade 1 Grade 2 Grade 3 Grade 4Neurologic Neuro: sensory none or no change mild paraesthesias; lossof deep tendon reflexes mild or moderateobjective sensory lossmoderate paraesthesias severe objectivesensory loss orparaesthesias thatinterfere with function —Neuro: motor none or no change subjective weakness;no objective findings mild objectiveweakness withoutsignificant impairmentof function objective weaknesswith impairment offunction paralysisNeuro: cortical none mild somnolence oragitation moderate somnolenceor agitation severe somnolence,(>50 % waking hours),agitation, confusion,disorientation orhallucinations coma, seizures, toxicpsychosisNeuro: cerebellar none slight incoordination,dysdiadochokinesia intention tremor,dysmetria, slurredspeech, nystagmus locomotor ataxia cerebellar necrosisNeuro: mood no change mild anxiety ordepression moderate anxiety ordepression severe anxiety ordepression suicidal ideationNeuro: headache none mild moderate or severe buttransient unrelenting and severe —Neuro: constipation none or no change mild moderate severe ileus > 96 hrsNeuro: hearing none or no change asymptomatic, hearingloss on audiometryonly tinnitus hearing loss interferingwith function butcorrectable withhearing aid deafness notcorrectableNeuro: vision none or no change — — symptomatic subtotalloss of vision blindnessPain Pain none mild moderate severe reg. narcoticsSkin Skin none or no change scattered macular orpapular eruption orerythema that isasymptomatic scattered macular orpapular eruption orerythema with pruritusor other associatedsymptoms generalisedsymptomatic macular,papular or vesiculareruption exfoliative dermatitisor ulcerating dermatitisAlopecia Alopecia no loss mild hair loss pronounced or totalhair loss — — Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 54 Radius Health, Inc. Confidential Category          Toxicity (units) Grade 0 Grade 1 Grade 2 Grade 3 Grade 4Allergy Allergy none transient rash, drugfever< 38 C (<100.4 F) urticaria, drug fever 38C (100.4 F), mildbronchospasm serum sickness,bronchospasmrequiring parenteralmedication anaphylaxisLocal Local none pain pain and swelling withinflammation orphlebitis ulceration plastic surgeryindicatedFever of unknownorigin Fever of unknownorigin none 37.1 - 38.0 C 98.7 -100.4 F 38.1 - 40.0 C 100.5 -104 F > 40.0 C (> 104 F)for less than 24hrs > 40.0 C (> 104 F)for more than 24 hrs oraccompanied byhypotensionInfection Infection none mild moderate severe life-threateningAdditional events Asthenia analogous toKarnofsky index(WHO grading) Chills analogous to fever Peripheral oedema analogous to weightgain Anorexia analogous to weightloss Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) 55o o o o o o o o o o o o o Exhibit 10.7(d) CLINICAL TRIAL SERVICES AGREEMENT AMENDMENT NO. 5 TO WORK STATEMENT NB-3 RADIUS HEALTH, INC., a Delaware corporation (“ Radius ”) and NORDIC BIOSCIENCE CLINICAL DEVELOPMENT VII A/S, a Danish corporation (“ NB”) that is a wholly-owned subsidiary of Nordic Bioscience Clinical Development A/S entered into a Clinical Trial Services Agreement dated March 29, 2011 (“Agreement” ) and Work Statement NB-3 under the Agreement ( “Work Statement NB-3” ) as of February 21, 2013 ( “Effective Date” ), and entered into anAmendment No. 1, Amendment No. 2, Amendment No. 3 and Amendment No. 4 to Work Statement NB-3 as of February 28, 2014, March 23, 2015, July 8, 2015and October 21, 2015 (as amended, “Work Statement NB-3”). Pursuant to Section 2.3, 2.11 and 11.7 of the Agreement, the parties wish to enter into this Amendment No. 5 to Work Statement NB-3 ( “ Amendment No. 5” )effective as of January 15, 2016 ( “Amendment Date” ). Capitalized terms used in this Amendment No. 5 and not defined herein are used with the meaningsascribed to them in the Agreement and Work Statement NB-3. The purpose of this Amendment no. 5 is to collect individual patient drug accountability log for patients in Radius’ BA058-05-003 clinical trial. NOW THEREFORE , in consideration of the mutual promises contained in the Agreement and for other good and valuable consideration the receipt andadequacy of which each of the parties does hereby acknowledge, the parties hereby agree to the terms of this Amendment No. 5 to Work Statement NB-3 asfollows: 1. Additional Monitoring Services: (a) At Radius’ request, NB will perform additional Monitoring Visits at the sites listed in section 1(b) to collect patient specific drug logs in Radius’ BA058-05-003 clinical trial. (b) NB shall collect drug logs at sites: 102, 103, 111, 121, 123, 124, 131, 132, 133, 141, 145, 151, 161 and 181. It is estimated that 45 monitoring days areneeded to collect the drug logs at the aforementioned sites. Other sites may be added to the list if the sites are not willing to make copies themselves. (c) NB shall coordinate drug log collection at all sites except US sites and site 101, including sites not mentioned in 1(b). This is done remotely by asking forthe site’s assistance in copying the drug logs and sending the documents to the appropriate individual. (d) Radius will compensate NB for the Monitoring Services as set forth in Attachment 1. All documents should be collected and sent to Radius by 29February 2016, if at all possible. This Amendment No. 5 to Work Statement NB-3 contains the following Attachments, each of which is made a part hereof: Attachment 1 – Budget Summary including Payment Schedule 2. Ratification.  Except to the extent expressly amended by this Amendment No. 5, all of the terms, provisions and conditions of the Agreement and WorkStatement NB-3 are hereby ratified and confirmed and shall remain in full force and effect. The term “Work Statement NB-3” , as used in the Agreement, shallhenceforth be deemed to be a reference to Work Statement NB-3 as amended by this Amendment No. 5. /s/GW  3.  General.  This Amendment No. 5 may be executed in counterparts, each of which will be deemed an original with all such counterparts together constitutingone instrument. IN WITNESS WHEREOF the parties have caused this Amendment No. 5 under Work Statement NB-3 to be executed by their respective duly authorized officers,and have duly delivered and executed this Amendment No. 5 under seal as of the Amendment Date. RADIUS HEALTH, INC. NORDIC BIOSCIENCE CLINICAL DEVELOPMENT VII A/S /s/ Gregory C. Williams /s/ Jeppe Ragnar AndersenBy: Gregory C. Williams By:Title: Chief Development Officer Title: CEO22 Jan 2016 Notice Address Notice AddressRadius Health, Inc. Nordic Bioscience Clinical Development VII A/S201 Broadway, 6 Floor Herlev Hovedgade 205-207Cambridge, MA 02139 2730 HerlevUSA DenmarkAttn: President & CEO Attn: CEO, Jeppe Ragnar AndersenPhone: 01.617.551.4700 Phone: 45.4452.5252Fax: 01.617.551.4701 Fax: 45.4452.521 2th  Attachment 1 - Budget Budget and Invoicing Schedule NB shall submit monthly invoices to Radius in accordance with the following on a work performed basis: · EUR 2,500 per monitoring day as per section 1(b) (not to exceed EUR 112,500) · EUR 150 per site not listed in section 1(b) for which NB coordinates collection of drug logs through the site staff. Details of the cost will itemized on theinvoice. It is anticipated that this will not exceed 8 sites (or EUR 1,200) · Any costs outside this agreement (i.e. additional fees required by sites for time and materials above the EUR 150) will be managed on a case-by-casebasis and must be approved by Radius. Pass-through includes shipping and office supplies. Shipping will wherever possible be done on Radius’s UPS account. /s/GW 3Exhibit 10.11(a) AMENDMENT NO. 3TODEVELOPMENT AND MANUFACTURING SERVICES AGREEMENT This Amendment No. 3 (the “Amendment”) to the DEVELOPMENT AND MANUFACTURING SERVICES AGREEMENT is entered into onDecember 31, 2015 by and between Radius Health Inc., a Delaware corporation, with its principal office at 950 Winter Street, Waltham, MA 02451, United Statesof America (“RADIUS”) and LONZA Sales Ltd, a Swiss company having an address at Muenchensteinerstrasse 38, CH-4002 Basel, Switzerland (together with itsAffiliates, “Manufacturer”) and upon execution will be incorporated into the Development and Manufacturing Services Agreement between RADIUS andManufacturer dated October 16, 2007 (the “Original Agreement”), as amended to date. Capitalized terms used in this Amendment will have the same meaning asset forth in the Agreement as amended to date. WHEREAS , RADIUS and Manufacturer are parties to the Agreement; and WHEREAS , RADIUS and Manufacturer are parties to Amendment No. 1, entered into on May 19, 2011, and Amendment No. 2, entered into onJanuary 30, 2014, to the Agreement (such Amendment No. 1 and Amendment No. 2 together with the Original Agreement, the “Agreement”); WHEREAS , the Parties are in the process of negotiating a commercial manufacturing services agreement (the “Commercial Agreement”); and WHEREAS , the Parties desire to further amend the Agreement as set forth herein. NOW THEREFORE , in consideration of the above premises and the mutual covenants herein set forth, and for other good and valuable consideration,the receipt and sufficiency of which are hereby acknowledged, the Parties hereto agree as follows: 1. Amendment to Section 14.1 . The Parties hereby agree to extend the term of the Agreement to the earlier of a) the date on which the CommercialAgreement becomes effective, or b) March 31, 2016, unless earlier terminated pursuant to Section 14 of the Agreement. Any further extensions of theterm shall be mutually agreed by the Parties. 2. Pending Work Orders . Any and all Work Orders entered into, or Purchase Orders issued, under and during the term of the Agreement which are stillpending at the time the Commercial Agreement becomes effective shall immediately become governed by, and incorporated in and made a part of, suchCommercial Agreement. 3. Ratification . All lawful actions taken by RADIUS and Manufacturer which are consistent with the terms of the Agreement are hereby authorized,approved and ratified, regardless of whether any such actions were taken prior to the date of this Amendment. 4. Remainder of Agreement . Except as modified by this Amendment, all other terms and provisions of the Agreement shall remain in full force and effectin accordance with their terms. 5. Entire Agreement . This Amendment and the Agreement supersede all other prior agreements, understandings, representations and warranties, oral orwritten between the parties hereto in respect of the subject matter hereof.  6. Governing Law; Jurisdiction . This Amendment shall be construed, interpreted and enforeced in accordance with the internal substantive laws of the Stateof New York, without reference to the choice of law doctrine of such state. 7. Counterparts; Delivery . This Amendment may be executed in any number of counterparts, each of which shall for all purposes be deemed an original andall of which shall constitute the same instrument. Delivery of an executed signature page of this Amendment by facsimile or other electronic transmissionsshall be as effective as delivery of an original executed counterpart of this Amendment. [Remainder of Page Intentionally Left Blank] 2 IN WITNESS WHEREOF, the Parties hereto have caused this Amendment to be executed by their respective authorized representatives effective as of thedate first above written. LONZA SALES LTD. RADIUS HEALTH, INC. By:/s/ Michael Maskus By:/s/ David C. HanleyName:Michael Maskus Name:David C. HanleyTitle:Associate Director Title:Executive Director, Technical Operations Commercial Development By:/s/ Cordula Altekrüger Reviewed ByName:Cordula Altekrüger CATitle:Senior Legal Counsel Legal Dept. 3Exhibit 21.1 SUBSIDIARY OF RADIUS HEALTH, INC. Legal Name of Subsidiary Jurisdiction of OrganizationRadius Health Securities Corporation Massachusetts QuickLinks -- Click here to rapidly navigate through this documentExhibit 23.1 Consent of Independent Registered Public Accounting Firm We consent to the incorporation by reference in the Registration Statement on Form S-3 (No. 333-201610) and Form S-8 (Nos. 333-177800 and 333-195521)of Radius Health, Inc. and in the related Prospectus of our reports dated February 25, 2016, with respect to the consolidated financial statements of RadiusHealth, Inc. and the effectiveness of internal control over financial reporting of Radius Health, Inc. included in this Annual Report on Form 10-K for the year endedDecember 31, 2015.Boston, Massachusetts February 25, 2016 /s/ Ernst & Young LLPQuickLinks Exhibit 23.1 Consent of Independent Registered Public Accounting Firm QuickLinks -- Click here to rapidly navigate through this documentExhibit 31.1 Certifications I, Robert E. Ward, certify that:1.I have reviewed this annual report on Form 10-K of Radius Health, 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 make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; 3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financialcondition, 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 and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in ExchangeAct Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for theregistrant and have: (a)Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, toensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within thoseentities, 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 designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for externalpurposes 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 conclusions about the effectivenessof the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and (d)Disclosed in this report any change in registrant's internal control over financial reporting that occurred during the registrant's most recent fiscalquarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect,the registrant's internal control over financial reporting; and 5.The registrant's other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to theregistrant's auditors and the audit committee of 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 which are reasonablylikely to adversely affect the registrant's ability to record, process, summarize and report financial information; and (b)Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal control overfinancial reporting.Date: February 26, 2016 /s/ ROBERT E. WARD Robert E. Ward President and Chief Executive OfficerQuickLinks Exhibit 31.1 Certifications QuickLinks -- Click here to rapidly navigate through this documentExhibit 31.2 Certifications I, B. Nicholas Harvey, certify that:1.I have reviewed this annual report on Form 10-K of Radius Health, 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 make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; 3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financialcondition, 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 and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in ExchangeAct Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for theregistrant and have: (a)Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, toensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within thoseentities, 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 designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for externalpurposes 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 conclusions about the effectivenessof the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and (d)Disclosed in this report any change in registrant's internal control over financial reporting that occurred during the registrant's most recent fiscalquarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect,the registrant's internal control over financial reporting; and 5.The registrant's other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to theregistrant's auditors and the audit committee of 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 which are reasonablylikely to adversely affect the registrant's ability to record, process, summarize and report financial information; and (b)Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal control overfinancial reporting.Date: February 25, 2016 /s/ B. NICHOLAS HARVEY B. Nicholas Harvey Senior Vice President, Chief Financial Officer, Treasurer andSecretaryQuickLinks Exhibit 31.2 Certifications QuickLinks -- Click here to rapidly navigate through this documentExhibit 32.1 CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 In connection with the Annual Report of Radius Health, Inc. (the "Company") on Form 10-K for the fiscal year ended December 31, 2015 as filed with theSecurities and Exchange Commission on the date hereof (the "Report"), I, Robert E. Ward, certify, pursuant to 18 U.S.C. § 1350, as adopted pursuant to § 906 ofthe Sarbanes-Oxley Act of 2002, that to my knowledge:(1)The Report fully complies with the requirements of section 13(a) or 15(d) of the Securities Exchange Act of 1934; and (2)The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company. A signed original of this written statement required by Section 906 has been provided to the Company and will be retained by the Company and furnished tothe Securities and Exchange Commission or its staff upon request.February 25, 2016 /s/ ROBERT E. WARD Robert E. Ward President and Chief Executive OfficerQuickLinks Exhibit 32.1 CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 QuickLinks -- Click here to rapidly navigate through this documentExhibit 32.2 CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 In connection with the Annual Report of Radius Health, Inc. (the "Company") on Form 10-K for the fiscal year ended December 31, 2015 as filed with theSecurities and Exchange Commission on the date hereof (the "Report"), I, B. Nicholas Harvey, certify, pursuant to 18 U.S.C. § 1350, as adopted pursuant to § 906of the Sarbanes-Oxley Act of 2002, that to my knowledge:(1)The Report fully complies with the requirements of section 13(a) or 15(d) of the Securities Exchange Act of 1934; and (2)The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company. A signed original of this written statement required by Section 906 has been provided to the Company and will be retained by the Company and furnished tothe Securities and Exchange Commission or its staff upon request.February 25, 2015 /s/ B. NICHOLAS HARVEY B. Nicholas Harvey Senior Vice President, Chief Financial Officer, Treasurer and SecretaryQuickLinks Exhibit 32.2 CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 

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