RedHill Biopharma Ltd. (NASDAQ/ TASE: RDHL)

Transcription

1 RedHill Biopharma Ltd. (NASDAQ/ TASE: RDHL) Analyst and Investor Webcast on TALICIA for H. pylori Infection Tuesday, October 30, 2018

2 Disclaimer and Forward Looking Statements 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. 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 we will not have sufficient working capital, risks relating to the initiation, timing, progress and results of the Company s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts, risks related to the Company s reliance on third parties to conduct key portions of its clinical trials, including data management services, and the potential for those third parties to not perform satisfactorily, that there will be delays in obtaining, or we will be unable to obtain, FDA or other regulatory approvals for our products, unable to establish collaborations, that our therapeutic candidates will not be commercially viable, or our inability to successfully market or generate sufficient revenues from the marketing of Donnatal, Mytesi, EnteraGam and/or Esomeprazole Strontium Delayed- Release Capsules 49.3 mg, and risks relating to our Expanded Access Policy (EAP), 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 22, 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, 2 future events or other factors

3 TALICIA for H. pylori infection Gilead Raday Chief Operating Officer, RedHill Biopharma 3

4 Agenda TALICIA for H. pylori infection Gilead Raday, Chief Operating Officer, RedHill First Phase III study (ERADICATE Hp) and confirmatory Phase III study (ERADICATE Hp2) with TALICIA for H. pylori infection Ira Kalfus, MD, Medical Director, RedHill H. pylori - epidemiology & the unmet medical need Prof. David Graham, MD, M.A.C.G., Principal Investigator of the ERADICATE Hp2 study H. pylori infection - market analysis & forecast Jerry Rosenblatt, PhD, RedHill Advisory Board Q&A 4

5 RedHill Biopharma - Highlights Emerging U.S. GI specialty company (NASDAQ/TASE: RDHL) Focused on development and commercialization in the U.S. of late clinical-stage drugs for GI diseases and cancer Robust Development Pipeline with Multiple Near-Term Milestones Three Phase III-stage GI drugs in development Multiple Phase II programs targeting high unmet medical needs Four commercial GI products in the U.S. with sales force of 40 5

6 Emerging U.S. Specialty GI Pharma - Robust Pipeline and Commercial Operation: Select Key Programs* Product Indication Pre-Clinical Phase I/II Phase III Marketed 4 COMMERCIAL PRODUCTS TALICIA (RHB-105) RHB-104 GI-Related Products H. pylori infection Crohn s disease Donnatal, Mytesi, EnteraGam and Esomeprazole Strontium DR Capsules Successful first US Phase III completed; Confirmatory US Phase III ongoing Positive top-line results from Phase III MAP US study RHB-204 NTM infections Pivotal Phase III study planned BEKINDA (RHB-102) Gastroenteritis IBS-D Positive results from Phase III U.S. study Positive results from Phase II U.S. study RHB-106 YELIVA (ABC294640) Bowel cleanser Multiple indications Worldwide rights licensed to Salix Pharmaceuticals Cholangiocarcinoma and other indications 6 * Estimated timeline/indication in the pipeline is subject to changes in development plans and regulatory requirements/clarifications, including complementary /additional studies ; 2 BEKINDA, YELIVA and TALICIA are proposed tradenames which are subject to FDA review and approval 3 For full prescribing information see: 4 Mytesi is an antidiarrheal indicated for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy (ART).For full prescribing information see: 5 EnteraGam (serum-derived bovine immunoglobulin/protein isolate, SBI) is a medical food which must be administered under medical supervision 6 For full prescribing information see:

7 H. pylori Resistance - Growing Global Health Problem H. pylori Infection Progressive gastro-duodenal damage peptic ulcer disease and gastric cancer * Highly prevalent: Approx. 50% of the world population, 30-40% of the U.S. population ** H. pylori Infection Top 10% GIs prescribing H.pylori treatments treat > 10 patients/week *** Muscularis mucosae Inflammation Gastric Ulcer Growing resistance to antibiotics Approx % eradication failure with SOC triple therapy **** WHO categorizes H. pylori (clarithromycin-resistant) as a pathogen of High Priority FDA Includes H. pylori in the GAIN Act - creating incentives for developing new drugs Acknowledgement of the need by GIs and payors 7 * Lamb A et al. Role of the Helicobacter pylori-induced inflammatory response in the development of gastric cancer. J Cell Biochem 2013 Mar;114(3):491-7; ** Chey WD et al. Management of Helicobacter pylori Infection. Am J Gastroenterol 2007;102: ; *** Company proprietary survey among U.S. GI specialists;**** Malfertheiner P. et al. Management of Helicobacter pylori infection - the Maastricht IV/ Florence Consensus Report, Gut 2012;61: ; Graham DY et al. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol Jun;5(6): and Graham DY et al. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 2010;59:

8 TALICIA - Next Generation Solution TALICIA (RHB-105) is a novel, patent-protected, all-in-one combination of two antibiotics and a proton pump inhibitor Little to no resistance of H. pylori to TALICIA antibiotics Unique dosing and PK profile of the rifabutin active - barrier to generic substitution All-in-one capsule allowing for improved convenience, compliance and single co-pay First Phase III study in the U.S. completed successfully: 89.4% H. pylori eradication with TALICIA * - Vs. 70% literature benchmark (p<0.001) - Vs. 63% eradication with SOC (p=0.006) ** - Safe and well tolerated 8 * mitt ** Post hoc analysis of open-label SOC treatment of patients in placebo-arm of the study

9 TALICIA - Next Generation Solution (Cont.) Final patient assessed for primary endpoint in confirmatory Phase III study - Top-line results expected by year-end 2018 FDA granted QIDP Designation to TALICIA under the GAIN Act: Fast-Track and eligibility for Priority Review and 8 years of market exclusivity Planned to be indicated as a first-line treatment for eradication of H. pylori infection regardless of ulcer status Subject to successful results - NDA filing expected early 2019 and potential product launch anticipated in H2/2019 Anticipated positioning as first-line best-in-class treatment to eradicate H. pylori 9

10 First Phase III study (ERADICATE Hp) and Confirmatory Phase III study (ERADICATE Hp2) with TALICIA Ira Kalfus, M.D. Medical Director, RedHill Biopharma 10

11 TALICIA All-in-one capsule formulation 4 capsules tid - 14 days treatment - Amoxicillin 1000 mg tid 3 gm daily - Rifabutin 50 mg tid 150 mg daily - Omeprazole 40 mg tid 120 mg daily >90% efficacy in amoxicillin/rifabutin/ppi single site standard-of-care failed treatment study * Minimal resistance noted to amoxicillin/rifabutin 11 * Borody et al., Aliment Pharmacol Therapy. 2006, 23,

12 Rationale for Development of TALICIA Increasing antibiotic resistance is a worldwide problem, with nearly 800,000 deaths per year due to gastric cancer * 30%-40% treatment failure with current SOC therapy H. pylori has been shown to be highly sensitive to rifabutin (a derivative of rifamycin) Rifabutin-based therapy could establish improved effectiveness of H. pylori eradication, including metronidazole- and/or clarithromycin-resistant strains Resistance of H. pylori to amoxicillin or rifabutin is very rare 12 *

13 ERADICATE Hp First Phase III Completed - Study Design Double blind placebo controlled study to assess the safety and efficacy of TALICIA in the treatment of confirmed Helicobacter pylori infection in dyspepsia patients - Negative ¹³C UBT days post treatment with TALICIA - 90% powered to detect a 20% treatment effect vs. 70% eradication rate as historical control 118 subjects in 9 sites 2:1 randomization 14 day treatment with blinded study drug Treatment failures received investigator directed therapy with follow-up test of cure post therapy 13

14 ERADICATE Hp First Phase III Completed Efficacy Results Primary Endpoint vs. historical control mitt TALICIA success rate 89.4% (59/66), p-value<0.001 SOC eradication rate (post-hoc) vs. TALICIA 63% (17/27 subjects), p-value=0.006 in mitt 14

15 ERADICATE Hp First Phase III Completed - Safety Adverse events comparable TALICIA vs. placebo 2 serious adverse events unrelated to study drug Anemia noted at screening - subject completed study (TALICIA arm) Perirectal abscess 18 days after completing study drug (placebo arm) 2 Early discontinuations in TALICIA arm Pharyngitis with poor compliance Nausea with poor compliance No deaths 15

16 ERADICATE Hp First Phase III Completed - Conclusions A novel 3 in 1 potential new therapy Safe, well tolerated and more effective than historical or physician selected SOC treatment Subject compliance and retention essential 16

17 ERADICATE Hp 2 - Confirmatory Phase III Study Ongoing Double-blind active comparator study to assess the safety and efficacy of TALICIA in the treatment of confirmed H. pylori infection - Negative ¹³C UBT post initiation of therapy - Sample size for this study has been calculated based on a superiority comparison assuming 83% effectiveness for the new treatment, and 70% effectiveness for the control, with 90% power and a 2-sided alpha of 5% 455 Subjects in 55 sites Randomized 1:1 TALICIA vs. active comparator Treatment failures received investigator directed therapy with follow-up test of cure post therapy 17

18 Primary Endpoint ERADICATE Hp2 Confirmatory Phase III Ongoing - Study Endpoints Occurrence of H. pylori eradication is confirmed via 13 C Urea Breath Test (UBT) testing days after initiation of treatment Secondary Endpoint (Efficacy) Antibiotic Resistance and Susceptibility Subgroup Analyses Pharmacokinetics Assess the difference in antibiotic resistance and susceptibility within treatment failure subjects Safety Endpoint Adverse events and clinically significant changes in laboratory values 18

19 ERADICATE Hp2 Confirmatory Phase III Ongoing - Exploratory and Additional Endpoints CYP2C19 status summarized and analyzed for efficacy using descriptive methods Eradication rates in failure to eradicate subjects who receive susceptibility directed standard of care will be analyzed descriptively First national survey of H. pylori susceptibility in many years 19

20 ERADICATE Hp2 Confirmatory Phase III Ongoing - Active Comparator Rationale High dose amoxicillin and PPI is an FDA approved regimen Combination drug policy requires demonstration of clinical benefit of rifabutin added to amoxicillin/ppi Active Comparator - total daily dose of: - Amoxicillin 3000 mg - Omeprazole 120 mg 20

21 ERADICATE Hp2 Confirmatory Phase III Ongoing - Statistical Powering FDA referenced high-dose amoxicillin/ppi studies demonstrated 61% and 70% efficacy H. pylori consensus statement powered TALICIA most clinicians may not know the prevalence of clarithromycin resistance in their local population (see statement 2). In such cases, given the evidence of inadequate eradication rates, they recommend that clinicians err on the side of caution and avoid PPI triple therapy containing clarithromycin (PAC, PMC) unless they have evidence of high success rates (>85%) in their community Eradicate Hp2 is powered to detect a 13 % treatment effect at 83% vs 70% in the ITT population 21 * The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults Gastroenterology 2016;151:51 69

22 ERADICATE Hp2 Confirmatory Phase III Ongoing Patient Population ITT as regulatory requirement with all randomized patients included in efficacy analysis ERADICATE Hp2 study goal of 100% retention as lesson learned from ERADICATE Hp first Phase III study with TALICIA Goal met: 453/455 patients completing test-of-cure Results by end of

23 H. pylori infection - Epidemiology & the Unmet Medical Need Prof. David Graham, M.D., M.A.C.G. Principal Investigator of the ERADICATE Hp2 Confirmatory Phase III study Renowned Researcher and Physician at the Baylor College of Medicine 23

24 Helicobacter pylori Gram-negative spiral bacteria Niche: human stomach 24

25 H. pylori Infection Transmissible infectious disease Acquired in childhood Disease manifestations usually in adults with variable latent periods High morbidity, modest mortality Curable 25

26 Outcomes of H. pylori Infection Environmental Factors Atrophic Gastritis Gastric Cancer Gastric Ulcer Acute Gastritis Acute-on-Chronic Gastritis Lymphoma Antral Predominant Gastritis Duodenal Ulcer Childhood Mid-life Old Age 26

27 27 Maastricht IV (2012) * Gut 2012;61:

28 Kyoto Global Consensus Report on H. pylori gastritis (2015) H. pylori gastritis should be defined as an infectious disease, even when patients have no symptoms and irrespective of complications such as peptic ulcers and gastric cancer. 28 * Gut 2015;64:1315

29 Helicobacter pylori H. pylori is an infectious disease It can be cured with antibiotics Cure of the infection alters the natural history of the associated diseases Treatment of infectious diseases with antibiotics should be straight forward 29

30 H. pylori - Treatment All effective infectious disease therapy is susceptibility-based Susceptibility testing is rarely available for H. pylori Most regimens are empiric 30

31 H. pylori Therapy - Rules of Thumb Two or more antibiotics Acid suppression Duration: 14 days Confirm cure (UBT or stool antigen test) 31

32 Antimicrobial Drugs Used for H. pylori Amoxicillin Bismuth Clarithromycin (macrolides) Metronidazole/Tinidazole Tetracycline Proton pump inhibitors Floroquinolones Rifabutin 32

33 Problem: H. pylori Resistance Clarithromycin Levofloxacin Metronidazole 33 *Aliment Pharmacol Ther 2016;43;514

34 Triple Therapy Any PPI 34 PPI & any 2 Clarithromycin Amoxicillin Metronidazole

35 Because of resistance the need for new drugs is becoming acute 35

36 Susceptibility Testing Available? Best Approach: 2018 Yes No Susceptibility Based Regimen Currently Unavailable Best Locally Available Regimen Empiric Therapy Use drugs for which resistance is rare 36

37 H. pylori infection - Market Analysis & Forecast Jerry Rosenblatt, PhD RedHill Biopharma Advisory Board Managing Partner, Foster Rosenblatt 37

38 The Seroprevalence of H. pylori Infection is Between 30-80%, Suggesting More Than 4B Patients are Infected Global Prevalence: 4.32B (US: 117M, EU5: 149M, JP: 66M) CAN: 36% (14M) MEX: 53% (69M) US: 36% (117M) SA: 46% (195M) EU5: 46% (149M) RoE: 47% (196M) Africa: 79% (962M) RoA: 54% (927M) India: 64% (860M) China: 55% (765M) Japan: 52% (66M) RoE: Rest of Europe RoA: Rest of Asia SA: South America 38 The major pharmaceutical markets (US, EU5 & JP) account for 8% of the global prevalent H. pylori patients; the majority of prevalent patients (>90%) are from the developing countries The majority of H. pylori patients are asymptomatic and thus, are undiagnosed and untreated Treatments are recommended for all individuals who test positive for H. pylori infection; however, testing is only routinely done in patients with active PUD, history of PUD, and gastric cancer Sources: Clarivate Analytics (formerly Thomas Reuter) Incidence & Prevalence Database (PID), Hooi et al. Gastroenterology, 2017; 153:

39 Over 27M People Worldwide are Prescribed 32M Rxs of Eradication Therapies for PUD and Related GI Disorders Global Treated Patients: 27M 3 (US: 2.5M 1,2, EU5: 3.2M, JP: 1.4M) CAN 0.3M Tx Patients 0.36M TRxs Mex 1.5M Tx Patients 1.8M TRxs US 2.5M Tx Patients 3.1M TRxs EU5 3.2M Tx Patients 3.9M TRxs RoE 4.3M Tx Patients 5.1M TRxs Africa 2.1M Tx Patients 2.5M TRxs RoA 2.0M Tx Patients 2.4M TRxs China 4.1M Tx Patients 5.0M TRxs 3 Treatment rate for other countries are estimated based on each country s H. pylori prevalence to US s H. pylori prevalence Japan 1.4M Tx Patients 1.7M TRxs 1 Annual TRx volume calculated based on 1.2 Rx per person per year, which corresponds to rate of eradication 2 US claims suggests 0.4% of US 0-65 y.o. population are prescribed eradication therapy, however, 0-65 y.o. makes up only 43.8% of all patients with PUD, therefore 2.7% of 65+ y.o. are prescribed eradication therapy, overall, 0.8% of the population are prescribed eradication therapy SA 0.4M Tx Patients 0.5M TRxs India 4.7M Tx Patients 5.6M TRxs 39 Treatments are recommended for all individuals who test positive for H. pylori infection In the US, approx. half of the Rx written for H. pylori eradication was for patients with abdominal symptoms of undetermined causes, and other half for PUD (11%), NUD (18%) and GERD (20%) Due to better drug access, major pharmaceutical markets (US, EU5 & JP) account for 27% of the global Rxs prescribed for H. pylori eradication 4 Sources: FR Analysis, Howden et al. Am J Manag Care, 2007, Feinstein et al. Emerg Infect Diseases, China, India. Africa, & RoW prescription Treatment Rate is calculated to be approximately 10% of the US based on the ratio of their population, drug price, and WW sales contribution

40 The Global Market For H. pylori Eradication Is Estimated At $4.8B, Of Which $1.4B (~30%) Is From The U.S. Global Market: $4.8B (US: $1.4B, EU5: $0.6B, JP: $0.3B) US Cost Assumptions (assuming DoT) India $494 China $440 RoW $837 Global Market Size in USD, MM 1 RoE $704 JP $275 US $1,420 EU5 $571 1 Market size calculated using US WAC prices from Symphony Health; prices are before discounts, coupons, vouchers, etc. EU5, RoE, and JP prices are estimated at 32.5%, 30.1%, and 35.4% of US prices, respectively. China, India and RoW prices estimated at ~20% of US prices Average $454 3 Pylera + PPI ~$1,148 Omeclamox-Pac ~$740 PrevPac ~$1,035 Gx Triple Therapy (PPI + two ~$238-$672 antibiotics) 2 Gx Quadruple Therapy (PPI + Bismuth + two antibiotics ~$532 2 Annual Triple therapies include: PAC (PPI, amoxi & clarithro BID), PMC (PPI, metro & clarithro BID), PAM (PPI, amoxi & metro BID) and PAL (PPI, amoxi & levo BID), price depends on the WAC prices of the components 3 Weighted average price calculated based on branded TRx share of 3%, and rest of the TRx split evenly between generic triple therapy and generic quadruple therapy 40 Although the major pharmaceutical markets (US, EU5 & JP) account for 8% of the global prevalent H. pylori patients, they make up 47% of the global H. pylori eradication market On average, US drugs are priced 3X higher than EU5, 2.5X higher than Japan, and 5x higher than RoW; therefore, although US makes up only 2.7% of the global prevalent patients, it contributes to 30% of the global market Sources: FR Analysis, Symphony Health Pharmaceutical Audit Suite (PHAST ) TRx/EUTRx/Sales Data, Redbook, Fallon et al. Gastroenterology, 2016; Chey et al. Am J Gastroenterol, 2017; Diery et al. Gastroenterology, 2007, Plyera PI, Omeclamox-PK PI, PrevPac PI, PMPRB 2017

41 TRx (in thousands) A Lack of Real Clinical Differentiation in the US Amongst Promoted Products Has Kept Branded Market Share at ~5.5% US Market: $1.4B (Branded: $0.08B, Generic: $1.3B) US Market Size in USD, MM 1 Branded or (Co-Packaged) $78 (5.5%) % 12% 10% US Market Demand 2 9% 8% 7% 6% 5% 4% 3% 16% 12% 8% 4% Share of Total Demand (%) 0 0% 41 Generic $1,342 1 Market size calculated using US WAC prices from Symphony Health; prices are before discounts, coupons, vouchers, etc. Pylera Branded PrevPac The branded products lack efficacy benefit while providing only modest convenience improvement over generic products, and their use is restricted to patients with PUD, which makes up ~10% of the patients The branded products also took aggressive price hikes and are placed unfavorably on formularies The majority of the Medicare plans, which covers over 50% of H. pylori eradication therapy treated patients, no longer cover these branded co-packaged products Sources: FR Analysis, Symphony Health Pharmaceutical Audit Suite (PHAST ) TRx/EUTRx/Sales Data, Redbook, Plyera PI, Omeclamox-PK PI, PrevPac PI Omeclamox-Pak Generic PrevPac 2 Top reasons why current branded product have low market share Similar efficacy compared to generic triple or quadruple therapies, and very modest convenient benefits Restricted label for patients with active or history PUD, which make up 10% of all patients treated with eradication therapy Aggressive price hikes resulted in unfavorable formulary placement (i.e. not covered by majority of Medicare plans)

42 TALICIA Has Significantly Differentiated Clinical Benefits, and Could Become the Future SoC for H. pylori Infection Eradication TALICIA clinical & commercial attributes comparison Generic Triple & Quadruple Therapies Branded Triple & Quadruple Therapies TALICIA (Fixed-Dose Rifabutin Triple Tx) FDA Approved Indication Not Indicated Narrow Indication - H. pylori infection with active or history of PUD Broad Indication - All H. pylori infection with or without PUD, and incl. treatment naïve patients Eradication Rates - Triple Tx: 61.5% - Quad Tx: 80.7% - Triple Tx: 61.5% - Quad Tx: 80.7% 89.4% Dosing Regimen Least Convenient - Triple Tx: 4 pills BID - Quad Tx: 3 pills QID + BID PPI More Convenient - PrevPac: 4 pills BID - Pylera: 3 pills QID + BID PPI Most Convenient - 4 fixed-dose pills TID Cost Burden - Triple Tx: $238-$672 - Quad Tx: $532 Plus dispensing fees - Pylera: $1,148 - PrevPac: $1,035 - Omeclamox-Pac: $740 - Considerable price elasticity Unlike the current branded therapies, TALICIA will be indicated for a broader patient population TALICIA has significantly higher eradication rate compared to current SoC, and it is the first real fixed-dose treatment (Pylera still requires concomitant treatment with a PPI) Given the clinical benefits of TALICIA it could be placed favorably on the formularies, thus becoming the future treatment of choice for H. pylori infection eradication 42 Sources: FR Analysis, 1 Venerito et al. Digestion, 2013; 88:33-45, Fashner et al. Am Fam Physician ; 91(4) : , Kim et al. Korean J Intern Med 2015;30: , Garza-Gonzalez et al., World J Gastroenterol 2014; 20(6): , Zagari et al., European Journal of Clinical Investigation, (1), e12857

43 43 Q&A

44 THANK YOU! 44 RedHill Biopharma Ltd. 21 Ha arba a St. Tel-Aviv, ,Israel info@redhillbio.com Web: Tel: