ASCO 2017 WEBCAST. Elacestrant (RAD1901) June, 4, 2017

Transcription

1 ASCO 2017 WEBCAST Elacestrant (RAD1901) June, 4, 2017 NASDAQ: RDUS Disclaimer: RAD1901 is an investigational agent Please refer to the ASCO 2017 poster for complete details

2 Safe Harbor Any statements made in this presentation relating to future financial or business performance, conditions, plans, prospects, trends or strategies and other financial or business matters, including expectations regarding the development and potential commercialization of our product candidates, clinical trial results, regulatory actions, potential collaborations, future revenues and operating expenses, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of In addition, when used in this presentation, the words may, could, should, anticipate, believe, estimate, expect, intend, plan, predict, target and similar expressions and their variants, as they relate to Radius Health, Inc. ( Radius ) or its management, may identify forward-looking statements. Radius cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Important factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include, without limitation, risks and uncertainties regarding the progress of abaloparatide-sc in the regulatory process in Europe and the timing of potential regulatory actions; progress in the development of our product candidates; our failure to secure and maintain relationships with collaborators; risks relating to clinical trials; risks relating to the commercialization of TYMLOS in the U.S., or potential commercialization of any of our proposed product candidates, if approved (such as marketing, regulatory, patent, product liability, supply, competition and other risks); dependence on the efforts of third parties; dependence on and potential challenges to our intellectual property; and risks that we may lack the financial resources and access to capital to fund our operations. Further information on the factors and risks that could affect Radius business, financial conditions and results of operations and could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation are contained under the caption risk factors in Radius Annual Report on Form 10-K for the period ended December 31, 2016, filed with the U.S. Securities and Exchange Commission (SEC) on February 24, 2017, along with Radius most recent quarterly and other reports filed with the SEC. The forward-looking statements represent Radius estimate as of the date of this presentation only, and Radius specifically disclaims any duty or obligation to update forward-looking statements. 2

3 Agenda 3 TOPIC Welcome PRESENTER Barbara Ryan, IR Elacestrant Update Breast Cancer Treatment Landscape Alison O Neill, MD, VP, Oncolcgy Clinical Development Gary Hattersley, PhD, Scientific Officer Commercial Opportunity Robert Ward, President and CEO Q&A 3

4 Elacestrant Update Maturing data presented at ASCO 2017 on the US Ph1 Dose Escalation & Expansion study Data Presented at ASCO 2017 Impressive single agent activity in heavily pre-treated ER+ breast cancer patients Objective Response Rate (ORR) of 23% in patients with RECIST measurable disease at baseline Clinical Benefit Rate (CBR) at 24 weeks of 42%* Median Progression Free Survival (mpfs) of 4.5 months* Responses documented in patients with prior fulvestrant therapy, prior CDK4/6i therapy and in patients with ESR1 mutations 15 patients continue on treatment as of April 28, 2017 * In patient group with mature data for estimation (Parts A+B) 4

5 Evaluation of elacestrant (RAD1901), a novel oral investigational, selective estrogen receptor degrader (SERD), for the treatment of ER positive (ER+) advanced breast cancer (mbc) Aditya Bardia 1, Peter Kabos 2, Richard Elledge 3, Dannie Wang 4, Jinshan Shen 4, Fiona Garner 4, Alison O'Neill 4, Virginia G. Kaklamani 3 1 Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; 2 University of Colorado Denver, Greenwood Village, CO; 3 CTRC, University of Texas Health Science Center San Antonio, San Antonio, TX; 4 Radius Health Inc., Waltham, MA 5

6 Phase 1 dose escalation and expansion study design Study Objectives Primary: define recommended Phase 2 dose Secondary: safety and tolerability, pharmacokinetics (PK), preliminary anti-tumor effect, and evaluation of circulating tumor DNA (ctdna; exploratory objective) Response evaluations performed every 8 weeks following RECIST v1.1 guidelines Patient population ER+/HER2- postmenopausal women with mbc 2 prior chemotherapies in the advanced or metastatic setting No limit on number of prior endocrine therapies 6

7 Patient Demographics Median of 3 prior systemic therapies 38% had previously received fulvestrant 40% had previously received CDK4/6 inhibitor therapy 30% had received >1 prior line of chemotherapy 50% were ESR1 mutant 7

8 Objective Response Rates (ORR) in ER+ Advanced Breast Cancer for Endocrine Agents Range from 2.1%* (mono) to 19%* (in combo) 25% SERD combo mtor combo 3 rd line 0% 7-9% Fulvestrant (SOFEA, PALOMA-3) 2.1% Fulvestrant (BELLE-3) monotherapy ORR *ORR is based on ITT 8

9 Objective Response Rates (ORR) in ER+ Advanced Breast Cancer for Endocrine Agents Range from 2.1%* (mono) to 19%* (in combo) 25% SERD combo mtor combo 3 rd line 0% 19% Fulvestrant +Palbociclib (PALOMA-3) 9.5% Exemestane + Everolimus (BOLERO-2) 7-9% Fulvestrant (SOFEA, PALOMA-3) 2.1% Fulvestrant (BELLE-3) monotherapy combinations ORR *ORR is based on ITT 9

10 Elacestrant single agent ORR 23% in heavily pre-treated patients 22 patients had RECIST measurable disease 5 confirmed partial responses 9 patients with stable disease Confirmed responses observed in patients with prior fulvestrant, prior CDK4/6i therapy, and ESR1mut as well as wildtype 10

11 Clinical Benefit Rates (CBR) in ER+ Advanced Breast Cancer for Endocrine Agents Range from 15.4%* (mono) to 67%* (in combo) 70% SERD combo mtor combo 3 rd line 0% CBR 32-40% Fulvestrant (SOFEA, PALOMA-3) 15.4% Fulvestrant (BELLE-3) monotherapy *CBR is based on ITT 11

12 Clinical Benefit Rates (CBR) in ER+ Advanced Breast Cancer for Endocrine Agents Range from 15.4%* (mono) to 67%* (in combo) 70% SERD combo mtor combo 3 rd line 0% CBR 67% Fulvestrant +Palbociclib (PALOMA-3) 51.3% Exemestane + Everolimus (BOLERO-2) 32-40% Fulvestrant (SOFEA, PALOMA-3) 15.4% Fulvestrant (BELLE-3) monotherapy combinations *CBR is based on ITT 12

13 Elacestrant single agent CBR at 24 weeks 42% in patient group with mature data set (Parts A+B) Fulv = prior fulvestrant treatment; CDK4/6 = prior CDK4/6 inhibitor treatment; ESR1 = ESR1 mutation detected at baseline; RECIST = patients with RECIST measurable disease. Radius Health, Inc. PROPRIETARY

14 Median Progression Free Survival (mpfs) in ER+ Advanced Breast Cancer for Endocrine Agents Range from 1.8 mo* (mono) to 9.5 mo* (in combo) 10 mo SERD combo mtor combo 3 rd line mo Fulvestrant (PALOMA-3, SOFEA ) 1.8 mo Fulvestrant (BELLE-3) monotherapy mpfs *mpfs is based on ITT 14

15 Median Progression Free Survival (mpfs) in ER+ Advanced Breast Cancer for Endocrine Agents Range from 1.8 mo* (mono) to 9.5 mo* (in combo) 10 mo SERD combo mtor combo 9.2 mo Fulvestrant +Palbociclib (PALOMA-3) 7.8 mo Exemestane + Everolimus (BOLERO-2) combinations 3 rd line mo Fulvestrant (PALOMA-3, SOFEA ) 1.8 mo Fulvestrant (BELLE-3) monotherapy mpfs *mpfs is based on ITT

16 Elacestrant single agent mpfs 4.5 months in patient group with mature data set (Parts A+B*) *400 mg tablet data (Part C patients) is not mature for CBR or PFS estimates at this time **CBR at 24 weeks was calculated using the CBR population (ie. all 400mg patients in Part A+B who had at least 1 post baseline RECIST evaluation) 16

17 Most common ( 10%) treatment-related adverse events Elacestrant 400 mg administered orally on a continuous daily schedule was well tolerated Longest 400mg treatment duration now exceeds 1 year Predominantly G1 and G2 upper GI events (nausea, dyspepsia, vomiting) Profile supportive of potential for combination with other agents The two patients with G3 transaminase elevations had liver metastases; elevations were transient in one and associated with progressive disease in the liver in the second Radius Health, Inc. PROPRIETARY 17

18 What is an IDEAL profile for a SERD? Targeted potent ER receptor degrader Effective in treating resistant disease including ESR1 mutants Safety profile that allows for drug combinations eg: SERD+ CDKi s PK profile that allows for once a day oral dosing 18

19 Elacestrant Demonstrates Complete ERa Degradation Comparison with Other Investigational SERDs Human ER+ Breast Cancer Cell Line (MCF7) Cells were treated for 48 hours RAD1901 (nm) AZD9496 (nm) RAD1901 (nm) GDC-0810 (nm) RAD1901 (nm) Bazedoxifene (nm) V V V ERα Vinculin Elacestrant has shown superior activity than comparator oral SERDs 19

20 Elacestrant Demonstrates Complete Tumor Growth Inhibition Comparison with Other Investigational SERDs ESR1 Mutant Fulvestrant-Resistant Patient Derived Xenograft Model F u lv e s tra n t C o n tr o l G D C PDX: ST941 Patient Rx history: Aromatase inhibitor ESR1: Y537S T u m o r V o lu m e (m m 3 ) A Z D Fulvestrant: 3mg/dose every week Elacestrant: 60mg/kg daily GDC-810: 100mg/kg daily AZD9496: 5mg/kg daily Comparable to current clinical doses Produces greatest efficacy in models E la c e s tra n t D a y Elacestrant has shown superior suppression of tumor growth compared to fulvestrant, AZD9496, and GDC

21 Potential Combination Targets for SERDs Targeted therapies may be combined with Elacestrant (RAD1901) to improve clinical outcomes PI3K Inhibitors mtor Inhibitors Immuno- Oncology Agents CDK Inhibitors SERD PARP Inhibitors BCL2 Inhibitors HDAC Inhibitors 21

22 Elacestrant as a BEST in class SERD Elacestrant demonstrates complete ER degradation ü Elacestrant inhibits tumor growth in resistant models, including those that are ESR1 mutant ü Elacestrant has a well tolerated safety profile ü Elacestrant has a PK profile that supports once a day oral dosing ü 22

23 Elacestrant Update Maturing data presented at ASCO 2017 on the US Ph1 Dose Escalation & Expansion study Data Presented at ASCO 2017 Impressive single agent activity in heavily pre-treated ER+ breast cancer patients Objective Response Rate (ORR) of 23% in patients with RECIST measurable disease at baseline Clinical Benefit Rate (CBR) at 24 weeks of 42%* Median Progression Free Survival (mpfs) of 4.5 months* Responses documented in patients with prior fulvestrant therapy, prior CDK4/6i therapy and in patients with ESR1 mutations 15 patients continue on treatment as of April 28, 2017 * In patient group with mature data for estimation (Parts A+B) 23

24 Endocrine therapies in second line advanced breast cancer phase III trials Ther Adv Med Oncol 2015, Vol. 7(6)

25 Hormone Receptor Positive Breast Cancer and potential value of an ORAL SERD Hormonal Therapies and Development of Endocrine Resistance Adjuvant 1 st Line 2 nd Line 3 rd Line Tamoxifen Aromatase Inhibitors Aromatase Inhibitors Tamoxifen Fulvestrant Fulvestrant AI s Progestin PFS* 9-13 mths 3-4 mths <3 mths Endocrine Resistance Alterations of ER itself Loss due to ESR1 silencing Constitutional activation of ER due to ESR1 mutations/ fusion events Up-regulation of alternative signal transduction pathways Source: MDACC (Hortobagyi, * S Johnston, SABCS 2016 plenary) 25

26 Hormonal agents have shown a consistent volume growth because of broad use, potentially extended duration of therapy and combo dosing SERD Unit Volume* 350,000, ,000, ,000, ,000, ,000,000 Unit Volume per Hormone Agent* 3,000,000 2,500,000 2,000,000 1,500,000 1,000, , ,000,000 50,000, AI SERM SERD Introduction of an Oral SERD will accelerate adoption across all lines of treatment and in combination therapies * IMS: NSP ( ) 26

27 Elacestrant Potential Opportunity in ER+ Breast Cancer Patient estimates: US only Illustrative example Adjuvant BC K pts Patient numbers 1 st L Adv BC 35-40K patients 2 nd L Adv BC 30-35K patients 3 rd L Adv BC 26-30K *Arimidex peak sales $1.9B *Current Faslodex (inj) $0.8B in sales Potential use of oral SERD either as mono or all oral combo regimens * Projected global sales 27

28 Highlights and Upcoming Milestones FDA Approval of TYMLOS April 28, 2017 CHMP opinion on MAA for abaloparatide-sc in July 2017 Ex-US/ROW partnership for abaloparatide-sc by time of EU launch Report topline results for 24 month ACTIVExtend trial Q2 17 FDA meeting scheduled for Ph 2 study for elacestrant Q2 17 Initiate first in human trial for RAD140 in HR+ breast cancer in 2H 17 28