RedHill Biopharma Ltd. ( RDHL )

Transcription

1 RedHill Biopharma Ltd. ( RDHL ) Corporate Presentation January 2018

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. 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, that there will be delays in the initiation and progress of our studies, trials or other therapeutic candidate development efforts or 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, that the products that we promote in the U.S. may not generate sufficient revenues 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 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 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 3 Phase III-stage GI drugs in development Multiple Phase II programs targeting high unmet medical needs 3 GI products promoted by sales force of 40 in the U.S. 3

4 Emerging U.S. Specialty GI Pharma - Robust Pipeline and Commercial Operation: Select Key Programs Product ** Indication Pre-Clinical Phase I/II Phase III Marketed Donnatal EnteraGam IBS and acute enterocolitis *** Chronic diarrhea and loose stools **** U.S. CO-PROMOTION U.S. EXCLUSIVE LICENSE Esomeprazole Strontium DR Capsules TALICIA (RHB-105) GERD and other GI conditions ***** H. pylori infection U.S. COMMERCIALIZATION LICENSE Successful first U.S. Phase III completed; Confirmatory U.S. Phase III ongoing RHB-104 Crohn s disease NTM infections Phase III MAP US study and Phase III MAP US2 extension study ongoing 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) Upamostat (MESUPRON) Bowel cleanser Multiple indications Oncology/GI Worldwide rights licensed to Salix Pharmaceuticals Cholangiocarcinoma and other indications Completed multiple clinical studies 4 * Estimated timeline/indication in the pipeline is subject to changes in development plans and regulatory requirements/clarifications, including complementary /additional studies ** BEKINDA, YELIVA and TALICIA are proposed tradenames which are subject to FDA review and approval *** 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 prescribing information see: e09c a&type=display

5 Emerging Specialty U.S. GI-Focused Pharma Commercialization of RedHill s products A Leading U.S. GI-Focused Pharmaceutical Company x New GI-Products planed to be In-Licensed TALICIA (RHB-105) H. pylori infection RHB-104 NTM BEKINDA 24 mg Gastroentiritis BEKINDA 12 mg IBS-D RHB-104 Crohn s disease YELIVA Cholangiocarcinoma YELIVA GI MESUPRON Oncology/GI Donnatal IBS and acute enterocolitis EnteraGam Chronic diarrhea and loose stools Esomeprazole Strontium DR Capsules 49.3 mg GERD and other GI conditions # of Marketed Products *Presented events are forward looking statements and estimates, and are subject to uncertainties including, among others, clinical and regulatory outcomes, marketing approvals, financial resources, and commercial viability; This slide and strategic plan is made for illustrative purposes only. Please see Disclaimer and Forward Looking Statements.

6 Planned Near-Term Milestones Product Study Planned RHB-104 NTM Infections Pivotal U.S. Phase III Initiation H1/2018 RHB-104 Crohn s Disease MAP US Phase III Ongoing Top-Line Results Mid-2018 TALICIA (RHB-105) H. pylori Eradication Confirmatory U.S. Phase III Ongoing Top-Line Results H2/2018 6

7 Experienced Leadership Team Executive Management* Dror Ben-Asher, CEO P.C.M.I. Ltd. Adi Frish, Senior VP Business Development & Licensing Y. Ben-Dror, MediGus Reza Fathi PhD, Senior VP R&D XTL, PharmaGenics, Harvard Inst. of Chem. & Cell Biology Patricia Anderson, VP Regulatory Affairs MAPI Group, OptumInsight, Bayer, Novopharm Ira Kalfus MD, Medical Director Lev Pharmaceuticals, Aetna/US Healthcare Terry F. Plasse MD, Medical Director Rhone Poulenc-Rorer, Cytokine PharmaSciences Mark L. Levitt, MD, PhD, Medical Director, Oncology Teva, Sheba Medical Center, NIH Aida Bibliowicz, VP Clinical Affairs Europe MSc Technion, MBA TAU, Cato Research Israel Bruce P. Burnett, PhD, VP of Medical Affairs Entera Health, Primus Pharma, University of Colorado Gilead Raday, Chief Operating Officer MSc Neurology, MBE Cambridge, Sepal Pharma Guy Goldberg, Chief Business Officer Eagle Pharma, ProQuest, McKinsey Micha Ben Chorin, Chief Financial Officer GVT, Pyramid Analytics, Starhome B.V. Shani Maurice, VP Business Development & Communications Prime Minister s Office Clara Fehrmann, Director Clinical Operations Merck Canada, Santhera Pharmaceuticals, ICON Danielle Abramson, PhD, VP IP & Research PhD Medical Sciences Brown, Patent Agent Greenberg Traurig Craig Miller, VP US Business Operations, Market Access Salix, Oclassen Pharmaceuticals, Watson Pharmaceuticals Valerie Graceffa, VP US Sales and Marketing Aurora Diagnostics, Warner Chilcott, TRAK Group Cincinnati David Wasserman, VP Compliance Officer, US Operations Salix, Watson Pharmaceuticals, Glaxo PLC 7 * Personal background relates to selected former and current positions and education

8 Experienced Leadership Team Board of Directors * Dror Ben-Asher, CEO P.C.M.I. Ltd. Eric Swenden Alterphama nv, Lifeline Scientific Kenneth Reed, MD Dermatologist; Director Minerva Biotechnologies Shmuel Cabilly, PhD Scientist, Director in several life-science companies Nicolas Weinstein Water Bear Investments, EMC2, Abbott, CFR Dan Suesskind Teva, CFO, Director Rick D. Scruggs Salix, Watson, Oclassen Ofer Tsimchi Danbar, Polysack, Director in several companies Nurit Benjamini Wix, Coppergate Communications, Compugen Advisory Board * Jeff Leighton, PhD Glaxo, Exogen, Genesis, Inspire Werner Tschollar, MD Past SVP for Worldwide R&D, Novartis Joshua Schein, PhD Past CEO and co-founder, Lev Pharma June Almenoff, MD Furiex Pharmaceuticals, GSK Prof. Chezy Barenholz, PhD Prof., Hebrew University of Jerusalem, Co-inventor of Doxil Mr. Abe Schwartz Covalon Tech., CEO Cedara Software Prof. Colin Blakemore, PhD Oxford, Past CEO - UK Medical Research Council Prof. Ran Oren, MD Digestive and Liver expert, Hadassah Prof. Thomas Borody, MD Founder Centre for Digestive Diseases Jerry Rosenblatt, PhD IIBD Consulting, IMS Health Scott Harris, MD Lyric, Avaxia, Ocera, Napo 8 * Personal background relates to selected former and current positions and education

9 Financial Highlights* RedHill Biopharma Ltd. Symbol: NASDAQ: RDHL Tel-Aviv Stock Exchange: RDHL Market Cap (approx.) $109 million Ordinary Shares Outstanding million (Equivalent to approx million ADSs traded on NASDAQ) Estimated Cash and Short Term Investments (approx.) at the end of 2017 $45 million 9 * Financial information as of January 15, 2018 unless otherwise noted

10 U.S. GI-Specialty Pharma RedHill initiated U.S. promotion of Donnatal and EnteraGam in June 2017 and of Esomeprazole Strontium DR Capsules 49.3 mg in September 2017 RedHill Biopharma Inc. Highly Trained & Motivated Sales Force A wholly owned subsidiary with offices in Raleigh Durham, NC 40 sales reps promoting Donnatal, EnteraGam and Esomeprazole Strontium DR Capsules 49.3 mg in select U.S. territories Initial Net Revenues Approximately $1.5M in Q3/2017 RedHill s GI Development Programs Additional License Opportunities Commercial operations are planned to pave the way for the potential future commercial launch of RedHill s Phase III-stage GI development programs (TALICIA /RHB-104/BEKINDA ) RedHill continues to pursue licensing and acquisition of additional commercial product opportunities in the U.S. specialty GI area 10

11 TALICIA (RHB-105) A new combination therapy for treatment of H. pylori infection - with QIDP designation, including Fast-Track development status Confirmatory Phase III Study Ongoing Successful First Phase III Study Completed - Met Primary Endpoint with High Statistical Significance 11

12 TALICIA (RHB-105) - First Line Treatment for H. pylori Planned Indication Drug First line treatment for eradication of H. pylori regardless of ulcer status A novel combination of two antibiotics and a PPI (proton pump inhibitor): rifabutin, amoxicillin and omeprazole - in a single oral capsule Potential Advantages Potential higher efficacy than current standard of care in eradication of H. pylori strains resistant to standard care Potential to become a leading first line treatment Significantly broader indication than that of current therapies, with a larger potential patient population All-in-one capsule: convenient regimen - potentially improved compliance QIDP Status TALICIA received FDA QIDP designation under the GAIN Act for serious or lifethreatening infections, including Fast-Track development, Priority Review, and extended market exclusivity for a total of 8 years Market Size 2015 U.S. and global market estimated at approximately $1.45 billion and $4.83 billion respectively* 12 * Jerry Rosenblatt, Ph.D., a member of RedHill s Advisory Board and Partner at Foster Rosenblatt, RedHill Biopharma press release: RedHill Biopharma s Investor Webcast Forum Provides Update on the RHB-105 Phase III Program and Potential H. Pylori Eradication Market, May 18, 2015

13 TALICIA (RHB-105) (H. pylori) - Increasing Global Disease H. pylori Infection Progressive gastro-duodenal damage Helicobacter pylori (H. pylori) infection is the strongest risk factor for the development of gastric cancer * and peptic ulcer disease, and is associated with iron deficiency, B12 deficiency and drug malabsorption Gastric cancer is one of the leading causes of cancer deaths worldwide accounting for ~700,000 deaths per year Prevalence of H. pylori infection in the U.S. is estimated at 30-40% of the population - over 100 million people **, with an estimated 3 million patients treated annually *** H. pylori Infection Standard therapy fails in approximately 30% of patients who remain H. pylori positive due to growing resistance of H. pylori to clarithromycin and metronidazole - antibiotics commonly used in standard combination therapies **** Muscularis mucosae Inflammation Gastric Ulcer 13 * 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 analysis; **** 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:

14 World Health Organization: Urgent Need for New Antibiotic Treatments H. pylori Ranked as High Priority 14 February 2017 WHO published a global priority pathogens list of antibiotic-resistant bacteria to help in prioritizing the R&D of new and effective antibiotic treatments The purpose was to identify the most important resistant bacteria at a global level for which there is an urgent need for new treatments The list included 12 pathogens prioritized in 3 categories - Critical, High and Medium H. pylori (clarithromycin-resistant) was categorized as a pathogen for which there is a High Priority need to develop new treatments Enterococcus faecium, vancomycin-resistant Staphylococcus aureus, methicillin-resistant, vancomycin intermediate and resistant Helicobacter pylori, clarithromycin-resistant Campylobacter, fluoroquinolone-resistant Salmonella spp., fluoroquinolone-resistant Neisseria gonorrhoeae, 3rd generation cephalosporinresistant, fluoroquinolone-resistant

15 TALICIA (RHB-105) (H. pylori) - Confirmatory Phase III Study Ongoing A Randomized, Double-Blind, Active Comparator, Two-Arm, Confirmatory Phase III Study ( ERADICATE Hp2 ), Comparing TALICIA Against a Regimen of Amoxicillin and Omeprazole Alone in the Treatment of Confirmed H. pylori Infection in Dyspepsia Patients, Regardless of Ulcer Status Number of subjects 444 Sites Duration of Study Treatment Primary Endpoint Up to 65 sites in the U.S. 14 days - The occurrence of H. pylori eradication in the TALICIA group compared to the active comparator group as confirmed via 13C Urea Breath Test (UBT) testing days after initiation of treatment Development Status - Top-line results expected H2/

16 A Randomized Placebo-Controlled Phase III Study ( ERADICATE Hp ) to Assess the Safety and Efficacy of TALICIA in the Treatment of Confirmed H. pylori Infection in Dyspepsia Patients, Regardless of Ulcer Status Number of Subjects 118 TALICIA (RHB-105) (H. pylori) - Successful First Phase III Study Completed Sites Duration of Study Treatment Primary Endpoint Positive Phase III Results 13 sites in the U.S. 14 days - The occurrence of H. pylori eradication as confirmed via 13C Urea Breath Test (UBT) testing days after completion of treatment - Superiority in eradication of H. pylori infection over historical standard of care efficacy levels of 70% effectiveness % efficacy in eradicating H. pylori infection with TALICIA (p< 0.001) - The study successfully met its protocol-defined primary endpoint - 63% eradication rate demonstrated in open-label treatment of patients in the placebo arm with SoC therapy for persistent H. pylori infection - supporting the potential superior efficacy of TALICIA over SoC 16 - No serious adverse events related to the drug were noted in the study

17 RHB-104 Groundbreaking combination therapy targeting MAP bacteria for treatment of Crohn s disease and potentially other autoimmune diseases First Phase III Study Ongoing in Crohn s Disease Planned Pivotal Phase III Study for the Treatment of Nontuberculous Mycobacteria (NTM) Infections under QIDP Designation 17

18 The Link between Crohn s Disease and MAP Growing evidence that intracellular mycobacteria play a crucial role in Crohn s disease MAP (mycobacterium avium subsp. paratuberculosis) is the causative agent of Johne s disease, an infectious disease in cattle, clinically and pathologically similar to Crohn s disease An intracellular pathogen that proliferates in monocytes/macrophages Extremely slow growing and widely pervasive in the environment Advances in diagnostic technology have led to increasingly higher identification of MAP in Crohn s diseases patients 92% (34/37 Crohn s disease patients by PCR) - Bull, J Clin Microbiol, % (52/60 Crohn s disease patients) - Shafran, Dig Dis Sci, 2002 Crohn s disease is a multifactorial disease Defective innate immunity to intracellular bacteria Mutations in the NOD2 gene are strongly associated with Crohn s disease Mycobacterial infections in humans are difficult to treat; Effective anti-mycobacterial agents require intracellular activity ATS/IDSA* and WHO advise triple antibiotic therapy for non-tuberculosis mycobacterial disease Crohn s disease * American Thoracic Society, Infectious Disease Society of America, World Health Organization Johne s disease 18

19 RHB-104 (Crohn s) - First Phase III Study Ongoing Planned Indication The product Treatment of Crohn s disease in adult patients; Patent-protected combination of 3 antibiotics (clarithromycin, clofazimine and rifabutin) in a single oral capsule with potent intracellular, antimycobacterial and anti-inflammatory properties Market Size Worldwide market exceeded $7.6 billion in 2016 * Several clinical trials were conducted with earlier formulations of the drug, including two Phase II (2002 and 2005), a Phase III (published 2007) and a pediatric study (2013) in Australia; Preliminary positive safety results in a Phase I study (2014) Development Status First Phase III study ongoing; Enrollment completed and top-line results expected mid-2018 Open-label Phase III extension study (MAP US2) ongoing - intended to assess the safety and efficacy of RHB-104 in patients who completed 26 weeks of treatment in the MAP US study and remain with active Crohn s disease (CDAI>150) at week 26 Planned initiation of two additional ex-u.s. small-scale (20 subjects each) open-label clinical studies to evaluate RHB-104 s efficacy in newly diagnosed and treatment-naïve patients Diagnostics Diagnostic test for Mycobacterium Avium Paratuberculosis in development with Q 2 Solutions 19 * EvaluatePharma, estimated market for diagnosis and drug treatment of Crohn s disease, January 2017

20 RHB-104 (Crohn s) - First Phase III Study Ongoing Multi-center, randomized, double-blind, placebo-controlled, parallel group study (the MAP US Study ) to assess the efficacy and safety of fixed-dose combination RHB-104 in subjects with moderately to severely active Crohn s disease Number of Subjects Approximately 325 Sites Up to 150 sites in the U.S., Canada, Europe, Australia, New Zealand and Israel Primary Endpoint State of remission at week 26 Secondary and Exploratory Endpoints - State of response at 26 weeks - Maintenance of remission through week 52 - Efficacy outcome measures in relation to presence of MAP infection - Safety Phase III MAP US Development Status Phase III MAP US2 Extension Study - Unanimous positive recommendations from two DSMB meetings to continue the study (Dec safety focused, July safety and efficacy) - Patient enrollment completed November Top-line results expected mid-2018 Open-label Phase III extension study to the MAP US study ongoing - Planned to enroll approximately subjects with CDAI>150 at 26 weeks; Subjects are eligible for up to one year of treatment with RHB

21 Australian Phase III (Pfizer) Study Showed Strong Signs of Efficacy* Original Study Relapse Endpoint Skewed denominator at week 16 Remission Endpoint Reanalysis Randomized denominator at time Patients (100%) Lancet Reanalysis* 213 Patients (100%) Active Arm Placebo Active Arm Placebo Patients not in remission excluded from study 102 Active + prednisolone Remission 66% (67/102) p = Placebo + prednisolone Remission 50% (55/111) 16 Weeks 102 Active + prednisolone Remission 66% (67/102) p = Placebo + prednisolone Remission 50% (55/111) Relapse 39% (26/67) p =.054 Relapse 56% (31/55) 52 Weeks Remission 40% (41/102) p =.003 Remission 22% (24/111) Relapse 24% (10/41) p =.14 Relapse 43% (12/28) 104 Weeks Remission 30% (31/102) p =.005 Remission 14% (16/111) 21 *Phase III study conducted by Pharmacia for Australian approval and published by Selby et al (2007), Gastroenterology 132: ; Reanalysis published by Behr and Hanley (2008), Lancet Infectious Diseases 8:344. including all subjects randomized at the beginning of the study, disregarding any occurrence following randomization

22 Australian Phase III (Pfizer) Study Data Would Have Compared Favorably to Remicade Remicade ACCENT I* Remission Endpoint Reanalysis (from Pfizer PIII Australian study) 213 Patients (100%) Active Arm Placebo Response at 2 Weeks 59% (113/192) 102 Active + prednisolone 111 Placebo + prednisolone Remission at 30 Weeks Remission at 54 Weeks 39% (44/113) All subjects=23% (44/192) 28% (31/113) All subjects=16% (31/192) Separate trials; Theoretical comparison Remission 66% (67/102) p =.017 Remission 40% (41/102) p =.003 Remission 50% (55/111) Remission 22% (24/111) Remission at 16 Weeks Remission at 52 Weeks Remission 30% (31/102) p =.005 Remission 14% (16/111) Remission at 104 Weeks 22 * Hanauer et al, (2002), The Lancet 359: study similar to the reanalysis conducted by Behr and Hanley

23 RHB Multiple Barriers to Entry Limited availability of clofazimine (distributed by the World Health Organization (WHO) and Novartis) and generally requires name based individual import permit or Expanded Access Program (EAP) process for use Robust global patent portfolio covering RHB-104, with additional claims being pursued 3 years (and potentially 5 years) data exclusivity for treatment of Crohn s disease Potential PK synergies of APIs administered in the RHB-104 formulation that disappear when administered concomitantly Lower concentrations of the triple combination of RHB-104 active components provide excellent synergistic anti-map growth activity compared to individual or dual combinations of the drugs* APIs are not available in doses being used in RHB-104 Superior regimen of an all-in-one capsule solution for patients and physicians (reduced co-pays, etc.) Physicians potential liability exposure and complicated ramp-up period 23 * Alcedo KP, Thanigachalam S, Naser SA. RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn s disease associated with Mycobacterium paratuberculosis, Gut Pathogens, 2016, 8:32.

24 RHB-104 for NTM (Nontuberculous Mycobacteria Infections) - Pivotal Phase III Study Planned to be Initiated H1/18 Planned Indication The Product - Treatment of pulmonary nontuberculous mycobacterium disease (NTMD) caused by MAC infection - Difficult to treat infection with no approved standard of care - QIDP Designation Granted: Including Fast-Track development, Priority Review, and extended market exclusivity for a total of 8 years - Patent-protected all-in-one combination of 3 antibiotic drugs (clarithromycin, clofazimine and rifabutin) each known to be active against NTM caused by MAC infection* Potential Advantages - On label, convenient, fixed-dose combination for first-line therapy - potentially a new standard-of-care for an underserved condition Market Size - U.S. market potential estimated at over $500 million in 2017 ** - Potentially de-risked program in light of proven activity of each of the antibiotics for NTM caused by MAC and the growing RHB-104 safety database Development Status - Ongoing discussions with FDA for design of a single pivotal Phase III study in support of NDA filing for first-line treatment - Planned initiation of the pivotal Phase III study in H1/ *Wassilew et al, RESPIRATION 2016 ** Foster Rosenblatt

25 RHB-104 for NTM - Background and Epidemiology NTM are a ubiquitous bacteria, mostly non-pathogenic but can cause human disease * Pulmonary manifestations account for 80-90% of NTM associated disease * Pulmonary NTM disease symptoms can include fever, weight loss, chronic or recurring cough, chest pain, blood in sputum and fatigue ** NTM have high levels of drug resistance and require long term dosing with three or more antibiotics ** New antimicrobial agents for NTM are urgently needed *** Approximately 80% of pulmonary NTM infections in the U.S. are associated with Mycobacterium avium complex (MAC) **** NTM is considered an Orphan Disease with an estimated 110,000 pulmonary NTM patients in the U.S. in 2017 ***** 25 *Wassilew et al, RESPIRATION 2016; **American Thoracic Society; *** Daley et al CHEST 2017; **** Prevots DR et al, Am J Respir Crit Care Med 2010; ***** Foster Rosenblatt/Company estimates

26 RHB-104 for NTM - Pivotal Phase III Study Planned to be Initiated H1/18 A single, pivotal Phase III study to assess the efficacy and safety of RHB-104 as a first-line treatment for pulmonary nontuberculous mycobacteria (NTM) infections caused by MAC Planned Initiation Pivotal Phase III Development Plan Patient Population Study Design H1/ Pending further discussion with FDA, a double-blind, placebocontrolled pivotal Phase III study in the U.S. is planned subjects; Newly diagnosed or recent repeat culture positive non-cavitary MAC disease - 1:1 randomization to RHB-104 vs. placebo - 6 month treatment for primary efficacy endpoint with continued follow up treatment for an additional 12 months - Primary endpoint: Sputum culture conversion at 6 months with demonstration of clinical significance 26

27 BEKINDA (RHB-102) A bi-modal extended release, once-daily, ondansetron BEKINDA 24 mg - Positive Results from a U.S. Phase III Study for Gastroenteritis/Gastritis - Met Primary Endpoint BEKINDA 12 mg - Positive Results from a U.S. Phase II Study for IBS-D - Met Primary Endpoint 27

28 BEKINDA 24 mg: Gastroenteritis & Gastritis - Positive First Phase III Results A Randomized, Double-Blind, Placebo Controlled, Parallel Group Phase III Study ( GUARD ) to Assess the Safety and Efficacy of BEKINDA 24 mg for the Treatment of Acute Gastroenteritis & Gastritis The Product Patent-protected, once-daily extended release oral tablet ondansetron 24 mg Number of Subjects 321 adults and children over the age of 12 Sites Primary Endpoint Potential Advantages Market Size 21 sites in the U.S. The absence of vomiting, without rescue medication and intravenous hydration, from 30 minutes post first dose of the study drug until 24 hours post dose - If approved for marketing by FDA, BEKINDA could become the first 5-HT3 antiemetic drug indicated for the treatment of acute gastroenteritis or gastritis in the U.S. - Long lasting (24H) oral treatment with the potential to reduce dehydration and hospital visits and stays - Approximately 179 million cases of acute gastroenteritis annually in the U.S., leading to an estimated 470,000 hospitalizations * - Worldwide potential market could exceed $650 million annually ** Development Status Positive top-line results from the Phase III study announced June the study successfully met the primary endpoint RedHill is designing a confirmatory Phase III study for acute gastroenteritis and gastritis 28 * Scallan E, Griffin PM, Angulo FJ, Tauxe RV, Hoekstra RM. Foodborne Illness Acquired in the United States - Unspecified Agents. Emerg Infect Dis. 2011;17(1):16-22** Gres S. Nancy, Acute Gastroenteritis, Prim Care Clin Office Pract 40 (2013) and Company analysis

29 BEKINDA 24 mg: Gastroenteritis & Gastritis - Positive Phase III Results A Randomized, Double-Blind, Placebo Controlled, Parallel Group Phase III Study ( GUARD ) to Assess Safety and Efficacy of BEKINDA 24 mg for Treatment of Acute Gastroenteritis & Gastritis - The Phase III GUARD study successfully met its primary endpoint in the Intent to Treat (ITT) population (p = 0.04), despite high positive outcome rate in the placebo arm Results - ITT: BEKINDA 24 mg improved the efficacy outcome by 21%; 65.6% of BEKINDA 24 mg treated patients as compared to 54.3% of placebo patients (p = 0.04; n=192 in the BEKINDA group and n=129 in the placebo group) - PP: In patients who met all protocol entry criteria and for which the diagnosis of gastroenteritis was confirmed (n=177 in the BEKINDA group and n=122 in the placebo group), BEKINDA 24 mg improved the efficacy outcome by 27%; 69.5% of patients in the BEKINDA 24 mg group vs. 54.9% in the placebo group, (p = 0.01) - BEKINDA 24 mg was shown to be safe and well-tolerated; electrocardiogram results showed no adverse changes with treatment 29

30 BEKINDA 12 mg: IBS-D Positive Phase II Results A Randomized, Double-Blind, Placebo-Controlled, 2-Arm Parallel Group Phase II Clinical Study Designed to Evaluate the Safety and Efficacy of BEKINDA 12 mg in Patients Suffering from Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) The Product Number of Subjects Sites Primary Endpoint Market Size Development Status Patent-protected, once-daily extended release oral tablet ondansetron 12 mg 126 patients 16 clinical sites in the U.S. Response in stool consistency as compared to baseline, per FDA guidance definition - It is estimated that at least 30 million Americans may suffer from IBS, of which approximately 40% are of the IBS-D subtype * - The U.S. market grew by approximately 550% between , to an estimated $473 million in 2016, and is expected to continue to grow by approximately 14% annually ( ) ** - Positive top-line results announced October 2017; Study successfully met primary endpoint - FDA meeting planned for H1/2018 to discuss the design for one or two pivotal Phase III studies 30 * Lovell RM, Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis, Clin Gastroenterol Hepatol (2012), 10(7) ; Saito YA et al, The epidemiology of irritable bowel syndrome in North America: a systemic review, Am J Gastroenterol (2002), 97(8): ; ** EvaluatePharma

31 BEKINDA 12 mg: IBS-D Positive Phase II Results A Randomized, Double-Blind, Placebo-Controlled, 2-Arm Parallel Group Phase II Clinical Study Designed to Evaluate the Safety and Efficacy of BEKINDA 12 mg in Patients Suffering from Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) - Primary endpoint: The Phase II study successfully met its primary endpoint, improving the primary efficacy outcome of stool consistency response (per FDA guidance definition) by an absolute difference of 20.7% (p=0.036) Results % responders of subjects treated with BEKINDA (n=75) vs. 35.3% responders of the placebo subjects (n=51) - Secondary endpoints: 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 (combined stool consistency and abdominal pain response) - Safety: BEKINDA 12 mg was shown to be safe and well tolerated 31

32 YELIVA (ABC294640) Phase II-stage, first-in-class, orally-administered sphingosine kinase-2 (SK2) inhibitor targeting multiple oncology, inflammatory and GI indications 32

33 YELIVA (ABC294640) - Phase II-stage SK2 Inhibitor for Oncology, Gastrointestinal and Inflammatory Diseases The Product Potential Market A first-in-class, orally-administered sphingosine kinase-2 (SK2) inhibitor - with anti-cancer and anti-inflammatory activities, targeting multiple oncology, inflammatory and GI indications Significant market potential - multiple potential oncology, inflammatory and GI indications with a substantial unmet need - YELIVA completed numerous successful pre-clinical studies in oncology, GI- Inflammation and radioprotection models - Food effect study with YELIVA was successfully completed in healthy subjects - Repeat-dose toxicology studies provided favorable safety margins Development Status - Phase I study with YELIVA in cancer patients with advanced solid tumors successfully met its primary and secondary endpoints - Phase IIa study for the treatment of cholangiocarcinoma initiated December Orphan Drug Designation for the treatment of cholangiocarcinoma - Compassionate use for cholangiocarcinoma ongoing under Expanded Access Program - Phase I/II studies ongoing for the treatment of refractory or relapsed multiple myeloma and hepatocellular carcinoma (HCC) 33

34 YELIVA (ABC294640) - Phase II-stage SK2 Inhibitor for Oncology, Gastrointestinal and Inflammatory Diseases YELIVA (ABC294640) inhibits SK2, a lipid kinase that catalyzes formation of the lipid signaling molecule sphingosine 1-phosphate (S1P). By inhibiting S1P, YELIVA potentially inhibits tumor growth and proliferation and pathological inflammation YELIVA S1P promotes cancer growth and proliferation and pathological inflammation, including TNFα signaling and other inflammatory cytokine production Preliminary evidence suggests that because of its specificity for targeting SK2, rather than SK1, YELIVA may have a better therapeutic ratio than nonspecific sphingosine kinase inhibitors or those targeting only SK1 YELIVA Phase I study results demonstrated that administration of YELIVA resulted in a rapid and pronounced decrease in levels of S1P, with several patients having prolonged stabilization of disease 34

35 YELIVA (ABC294640) - Successful Phase I Study Met Primary and Secondary Endpoints A Phase I Clinical study of YELIVA in Cancer Patients with Advanced Solid Tumors Study Design - Open-label, dose-escalation, PK and PD, first-in-human Phase I study with YELIVA Site - Medical University of South Carolina Subjects - 21 patients with advanced solid tumors, the majority of which were GI cancer patients Endpoints - Primary endpoints: to identify the maximum tolerated dose (MTD) and the dose limiting toxicities (DLTs) and to evaluate the safety of YELIVA - The study included the first-ever longitudinal analyses of plasma S1P levels as a potential PD biomarker for activity of a sphingolipid-targeted drug - The study successfully met its primary and secondary endpoints Positive Phase I Results (June 2016) - YELIVA was found to be safe and well tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity - Administration of YELIVA resulted in a rapid and pronounced decrease in S1P levels - One patient had a prolonged partial remission and several patients had prolonged stabilization of disease - Of the three patients with cholangiocarcinoma, one had a partial response and the other two stable disease, one of whom for over a year 35

36 YELIVA (ABC294640) - Phase IIa Study for Cholangiocarcinoma Initiated A single-arm Phase IIa clinical study evaluating YELIVA as a single agent in patients with advanced, unresectable, intra-hepatic, perihilar and extra-hepatic cholangiocarcinoma Sites Mayo Clinic, MD Anderson Initiated December 2017 Number of subjects Up to 39 Lead Investigator Development status Dr. Mitesh J. Borad, MD, Associate Professor of Medicine and Director of Phase I Drug Development at the Mayo Clinic Cancer Center in Arizona - YELIVA was granted Orphan Drug designation for the treatment of cholangiocarcinoma - Compassionate use for cholangiocarcinoma ongoing under Expanded Access Program Primary endpoint - Response Rate (RR) - defined as CR+PR+SD of at least 4 months duration Market Size - Approximately 8,000 people are diagnosed with intrahepatic and extrahepatic bile duct cancers annually in the U.S. 36

37 RHB-106 Bowel preparation capsule Out-licensed to Salix Pharmaceuticals 37

38 RHB-106 (Bowel Preparation) - Licensed to Salix Pharmaceuticals Worldwide exclusive rights to RHB-106 were out-licensed to Salix Pharmaceuticals in February 2014 along with rights to other purgative developments* Planned Indication Preparation of the Gastrointestinal (GI) tract for GI procedures/surgeries (such as colonoscopy) The Product Patent-protected encapsulated formulation for bowel preparation Potential Advantages Potential Market Size Development Status Improved safety over existing encapsulated preparations on the market; No need to consume liquid solution; No bad taste Salix estimates peak year Rx share of 20% with annual sales of $280 million** - Phase IIa conducted in 62 patients in Australia*** - Salix assumed responsibility for future development of RHB * Salix Pharmaceuticals was acquired by Valeant Pharmaceuticals International in April 2015; ** Salix Pharmaceuticals Investor Day presentation, July 9, 2014; *** Borody et al (2006), Journal of Gastr and Hepat, 21: 87-88

39 UPAMOSTAT (MESUPRON) First-in-class small molecule targeting oncology and GI indications 39

40 Upamostat (MESUPRON) An S1 Serine Protease Inhibitor The Drug A first-in-class, orally-administered inhibitor of S1 family of trypsin-like serine proteases with potential for use in the treatment of cancer, inflammatory lung diseases, irritable bowel syndrome, inflammatory bowel disease and pancreatitis Licensed worldwide rights from Heidelberg Pharma (formerly Wilex), excluding China, Taiwan, Macao and Hong Kong Initially developed and described as a synthetic small molecule inhibitor of the serine protease urokinase plasminogen activator (Ki ~ 0.9µM) Established clinical safety profile from over 300 patients across 10 clinical studies, including Phase II studies in locally advanced pancreatic cancer and metastatic breast cancer Development Status FDA Orphan Drug Designation awarded for treatment of pancreatic cancer (October 2017) Intensive preclinical investigation sponsored by RedHill has revealed upamostat as a specific and potent inhibitor of human trypsin-3 (Ki ~ 20nM), trypsin-2 (Ki ~ 75nM), trypsin-6 (~100nM), trypsin-1 (Ki ~ 190nM) and matriptase-1 (~200nM) Planning underway to use the newly identified targets to select most appropriate indications, patients and drug combinations 40

41 Thank You! 41 RedHill Biopharma Ltd. 21 Ha arba a St. Tel-Aviv, ,Israel info@redhillbio.com Web: Tel: