RedHill Biopharma Ltd. (NASDAQ: TASE: RDHL)

Transcription

1 RedHill Biopharma Ltd. (NASDAQ: TASE: RDHL) BEKINDA Phase II Study for IBS-D Top-Line Results Conference Call and Webcast Tuesday, October 3 rd, 2017, 9 a.m. EDT

2 Disclaimer and Forward Looking Statements This presentation does not constitute an offer or invitation to sell or issue, or any solicitation of an offer to subscribe for or acquire any of the Company s securities or to participate in any investment in the Company. No representation or warranty is made to the accuracy or completeness of this presentation. You must make your own investigation and assessment of the matters contained herein. In particular, no representation or warranty is given, and the Company has no responsibility, as to the achievement or reasonableness of any forecasts, estimates, or statements as to prospects contained or referred to in this presentation. The theoretical comparison between the BEKINDA 12 mg Phase II study results and published data from studies of IBS-Dapproved therapies Xifaxan and Viberzi serves as a general benchmark for the effect size observed with BEKINDA 12 mg and should not be construed as a direct and/or equal comparison given that the studies were not identical in design, patient population and treatment duration and were not conducted head-to head in the same patient population. Statements in this presentation that are not historical facts (including statements containing "believes," "anticipates," "plans," "expects," "may," "will," "would," "intends," "estimates" and similar expressions) are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of These statements are not guarantees of future performance, are based on current expectations of future events and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements, including risks that the top-line results may change upon completion of independent review and analysis of the underlying data and completion of the Clinical Study Report, risks that there may be a halt in or delays in the progress of our studies and development plans, such studies and plans may not be successful, and there may be delays in obtaining FDA or other regulatory approvals for our products, or such approvals may not be obtained, among other risks. Additional information about the risk factors that may affect the realization of forward-looking statements is set forth in the Company s filings with Securities and Exchange Commission, including the Company s Annual Report on Form 20-F filed on February 23, If one or more of these factors materialize, or if any underlying assumptions prove incorrect, our actual results, performance or achievements may vary materially from any future results, performance or achievements expressed or implied by these forward-looking statements. You should not place undue reliance on forward-looking statements as a prediction of actual results. All forward-looking statements included in this presentation are made only as of the date of this presentation. We assume no obligation to update any written or oral forward-looking statement made by us or on our behalf as a result of new information, future events or other factors. 2

3 INTRODUCTION TO REDHILL BIOPHARMA Dror Ben-Asher CEO, RedHill Biopharma 3

4 Other Oncology /GI Inflammation GI & Inflammation Pipeline* Product ** Indication Pre-Clinical Phase I/II Phase III NDA/ Marketed Donnatal EnteraGam Esomeprazole Strontium DR Capsules TALICIA (RHB-105) IBS and acute enterocolitis *** Chronic diarrhea and loose stools **** GERD and other GI conditions ***** H. pylori infection U.S. CO-PROMOTION U.S. EXCLUSIVE LICENSE U.S. COMMERCIALIZATION LICENSE Successful first U.S. Phase III completed; Confirmatory U.S. Phase III ongoing RHB-104 BEKINDA (RHB-102) RHB-106 YELIVA (ABC294640) MESUPRON Crohn s disease NTM infections Gastroenteritis IBS-D Bowel cleanser Multiple indications Pancreatic cancer Phase III MAP US study and Phase III MAP US2 extension study are ongoing Pivotal Phase III study planned Successful top-line results from Phase III U.S. study Successful top-line results from Phase II U.S. study Worldwide rights licensed to Salix Pharmaceuticals Multiple Phase I/II studies ongoing and planned Completed Phase II studies including in pancreatic cancer 4 RIZAPORT (RHB-103) Migraine U.S. NDA filed - re-submission of NDA planned following CRL EUROPEAN MAA APPROVED UNDER THE EUROPEAN DECENTRALIZED PROCEDURE * Estimated timeline/indication in the pipeline is subject to changes in development plans and regulatory requirements/clarifications, including complementary /additional studies ** BEKINDA, YELIVA, RIZAPORT and TALICIA are proposed tradenames which are subject to FDA review and approval *** For further information see slide 10. For full prescribing information see: ****EnteraGam (a serum-derived bovine immunoglobulin/protein isolate, SBI) is a medical food which must be administered under medical supervision ***** for full information see slide 12; for full prescribing information see:

5 INTRODUCTION TO BEKINDA Gilead Raday COO, RedHill Biopharma 5

6 Agenda Introduction to BEKINDA Gilead Raday, RedHill COO BEKINDA 12 mg Phase II Study for IBS-D Top-Line Results Terry F. Plasse, MD, RedHill Medical Director IBS-D, the Unmet Medical Need and BEKINDA 12 mg M. Scott Harris, MD, Consultant to RedHill IBS-D Market Gilead Raday, RedHill COO Q&A 6

7 BEKINDA 12 mg & 24 mg Bi-modal, extended release, oral formulation of the 5-HT3 antagonist ondansetron Once daily administration - 24h coverage Patent-protected Composition of Matter and Method of Use patents with expiry in 2034 Two dose strengths: BEKINDA 12 mg for diarrhea-predominant irritable bowel syndrome (IBS-D) (Phase II) BEKINDA 24 mg for acute gastroenteritis/gastritis (Phase III) 7

8 BEKINDA 12 mg PHASE II STUDY FOR IBS-D Terry F. Plasse, MD Medical Director, RedHill Biopharma 8

9 BEKINDA 12 mg Phase II Study - Top-Line Results 126 patients with IBS-D per Rome III criteria, randomized 60:40 to receive BEKINDA 12 mg or placebo Average worst daily pain intensity 3.0 on scale of 0-10 No other explanation for symptoms Not currently on other therapy for IBS-D After 2 week baseline data collection, patients randomized and treated for 8 weeks Primary endpoint: Stool consistency Secondary efficacy endpoints: abdominal pain reduction and overall response Endpoints evaluated per 2012 FDA guidance Study was not powered for the secondary efficacy endpoints 9

10 BEKINDA 12 mg Phase II Study Demographic and Efficacy Results Parameter Active Placebo Difference P= N= Male/female % 29/71 31/69 Median age, years Efficacy Endpoints (mitt)* Stool consistency responders (Primary Endpoint) 54.7% 35.3% 19.4% 0.05 Abdominal pain responders 50.7% 39.2% 11.5% 0.28** Overall responders 41.3% 25.5% 15.8% 0.10** 10 * mitt population is the primary analysis group and is defined as all subjects who received at least 1 dose of study drug * * Study was not powered for these efficacy endpoints

11 BEKINDA 12 mg Phase II Study Safety Results No serious adverse events (AEs) No new or unexpected safety issues noted in the study Overall incidence of AEs similar in both arms Higher numbers of moderate/severe AEs recorded in the active arm, including some cases of constipation, an expected side effect In active arm, 3 patients had moderate and 1 had severe constipation Constipation was generally relieved by decreasing dosing frequency to every other day One patient with severe constipation discontinued study medication, after which the constipation resolved 11

12 BEKINDA 12 mg Phase II Study - Top-Line Conclusions 126 patients randomized to receive BEKINDA 12 mg or placebo The study successfully met its primary endpoint: improvement in stool consistency Clinically and statistically significant difference in the proportion of patients with improved stool consistency in the BEKINDA 12 mg as compared to the placebo arm While not powered for statistical significance of the secondary efficacy endpoints, the study suggested clinically meaningful improvement in both abdominal pain response and overall response Efficacy results compare favorably with previously reported outcomes from studies of Xifaxan (rifaximin) and Viberzi (eluxadoline)* Treatment was safe and well tolerated, with no unexpected side effects and no SAEs *The studies were not identical in design, patient population and treatment duration and were not conducted head-to head. 12

13 IBS-D, the Unmet Medical Need and BEKINDA M. Scott Harris, MD, MS, FACP, AGAF Consultant to RedHill Biopharma 13

14 Irritable Bowel Syndrome (IBS) - Overview A highly prevalent gastrointestinal disorder characterized by abdominal pain and altered bowel habits without an identifiable pathologic abnormality Disabling and unpredictable, with significant impact quality of life and productivity Between 5 and 30% of people suffer from IBS worldwide, including approximately 35 million people in the US One of the most common reasons to visit a physician Significant driver of utilization, with annual direct and indirect costs to the US economy exceeding $20 billion Recent drug approvals have set regulatory precedent, but a significant unmet need exists for new products 14 Schuster M, Am J Managed Care 2001; Sandler R, Gastroenterology 2002; Chang L, Aliment Pharmacol Ther 2004; Longstreth G, Gastroenterology 2006; Spiegel B, Curr Gastroenterol Rep 2009; FDA Guidance for Industry, May 2012; Cremonini F, Clin Gastroenterol Hepatol 2013; Enck P, Nature Reviews Dis Primers 2016; Buono J, Health and Quality of Life Outcomes 2017

15 Classification of IBS - 3 Subtypes Subtype Features Prescription Therapies One of three IBS subtypes, characterized by the predominant stool pattern Diarrhea-predominant IBS (IBS-D) Abdominal pain and bloating with diarrhea, urgency, often incontinence Lotronex (alosetron) Viberzi (eluxadoline) Xifaxan (rifaximin) Constipation-predominant IBS (IBS-C) Abdominal pain and bloating with hard stools, straining, overlap with idiopathic constipation Linzess (linaclotide) Amitiza (lubiprostone) IBS-C Predominantly constipation IBS-mixed Diarrhea & constipation IBS-D Predominantly diarrhea 40-60% IBS with mixed features (IBS-M) Alternating features of IBS-D and IBS-C Symptomatic treatment may be the mainstay of therapy In the US, IBS-D is the most frequent subtype, accounting for 40% to 60% of cases 15

16 The Spectrum of Prescription Drugs in IBS-D Drug Manufacturer Mechanism Comments Lotronex (alosetron) Licensed by GSK to Prometheus in HT 3 receptor antagonist Approved in 2000 for women with IBS-D. Withdrawn, then re-introduced under REMS program at a lower dose Limited to patients with severe, chronic symptoms who have not responded to other therapies Black Box warning for ischemic colitis and severe constipation Viberzi (eluxadoline) Acquired by Allergan in Forest buyout of Furiex in 2014 µ-opioid receptor agonist, d-opioid receptor antagonist Approved in 2015 for men and women with IBS-D Newly issued FDA warning regarding pancreatitis in patients with prior cholecystectomies Xifaxan (rifaximin) Acquired in the Valeant buyout of Salix in 2015 non-absorbed, broad spectrum antibiotic Approved in 2015 for men and women with IBS-D Use limited to 3 treatment courses (42 weeks) Carries concerns associated with long-term antibiotic use, including microbial resistance and superinfection There remains a clear, unmet medical need for effective new therapies in IBS-D 16

17 Comparative Difference in Effect Size of IBS-D Drugs in Phase II or III Clinical Trials Absolute Difference (Drug vs. Placebo) Stool Consistency Responder Abdominal Pain Responder BEKINDA (ondansetron) 12mg once daily Xifaxan (rifaximin) 550 mg three times daily Viberzi (eluxadoline) 100 mg twice daily 19.40% 10.50% 13.50% 11.50% 9.00% 5.00% Overall Responder 15.80% 9.50% 10.50% Footnotes: 17 BEKINDA 12 mg responder rates over 8 weeks, top-line data from Phase II study Xifaxan 550mg responder rates over 4 weeks following two weeks drug administration, averaged from Trial 1 & Trial 2 as reported in the FDA prescribing information Viberzi 100mg responder rates over 12 weeks, averaged from two phase III studies as reported in the FDA prescribing information A patient was characterized as a stool consistency or abdominal pain responder if he/she was a weekly responder for 50% of the planned weeks of treatment. Overall response was defined as patients who were both stool consistency and abdominal pain responders FDA Guidance for Industry, May 2012; Xifaxan Prescribing Information Nov 2015; Viberzi Prescribing information May 2015 The theoretical comparison between the BEKINDA Phase II study results and published data from studies of IBS-D approved therapies Xifaxan and Viberzi serves as a general benchmark for the effect size observed with BEKINDA and should not be construed as a direct and/or equal comparison given that the studies were not identical in design, patient population and treatment duration and were not conducted head-to head. Please also refer to Company s footnote #ii of October 3 rd 2017 press release

18 Ischemic Colitis and Constipation Associated with the Use of Drugs in the 5HT 3 class An earlier 5-HT3 antagonist, Lotronex (alosetron), was associated with ischemic colitis; the cause was unknown Ischemic colitis has not been reported with ondansetron over many patient years of patient use, nor with ramosetron, which is approved for the treatment of IBS-D in Japan. This indicates that this side effect was likely specific to Lotronex Constipation is not unexpected based on the mechanism of action of ondansetron 18

19 IBS-D and BEKINDA 12 mg Phase II Top-Line Results - Summary IBS-D is a chronic condition with a significant impact on quality of life, work productivity, physician visits and health care utilization A large, unmet need exists for new drugs in the treatment of IBS-D BEKINDA 12 mg demonstrated a very good safety profile in this Phase II study as well as impressive efficacy If both the safety and efficacy results are reproduced in a pivotal study, BEKINDA 12 mg has the potential, if approved, to become an important new therapy and standard of care of IBS-D 19

20 IBS-D: MARKET OVERVIEW Gilead Raday COO, RedHill Biopharma 20 The following slides are a summary of the slides prepared and presented by Jerry Rosenblatt, PhD, RedHill Biopharma Advisory Board, at RedHill Biopharma s R&D Day on BEKINDA, April 27, 2017

21 The Overall US IBS Market Is Estimated at $1.8B Current IBS Market The IBS-C market has been growing steadily since the introduction of Linzess in 2012 TRx market increased from 1.11M (2012) to 3.74M (2016), CAGR of 36% Sales ($) value increased from $296M (2012) to $1.37B (2016), CAGR of 47% The IBS-D market saw a dramatic increase after the introduction of Viberzi and Xifaxan 550 in 2015 TRx volume increased from 46,841 (2014) to 446,425 (2016), CAGR 112% Dollar ($) value increased from $2.8M (2014) to $402M (2016), CAGR of 423% Launch of Linzess (IBS-C) Launch of Viberzi & Xifaxan 550 (IBS-D) 21 Symphony TRx Data, Foster Rosenblatt

22 Forecast IBS Market The US Branded IBS Market is Forecast to Double by 2026 Reaching Roughly $5B; IBS-D Could Represent 40% of Sales The IBS market is forecast to grow significantly over the course of the next 10 years The TRx volume is forecast to increase from 4.2M in 2016 to 6M in 2026 (CAGR of 3.6%) The IBS-D market is expected to grow the fastest from 0.45M in 2016 to 1.3M in 2026 (CAGR 11.6%) The IBS $ value is forecast to increase from about $1.8B in 2016 to $4.7B in 2026 (CAGR of 10.2%)* The IBS-D $ value is forecast to increase from $400M in 2016 to $2B in 2026 (CAGR of 16.9%) 22 Symphony TRx Data, Foster Rosenblatt, *Market growth includes an annual 5% price increase

23 23 Q&A

24 THANK YOU! 24 RedHill Biopharma Ltd. 21 Ha arba a St. Tel-Aviv, ,Israel info@redhillbio.com Web: Tel: