RedHill Biopharma Ltd. · NASDAQ:RDHL
RedHill Biopharma — IPO Roadshow (November 2016)
65 slides from RedHill Biopharma's IPO roadshow presentation, Nov 1, 2016
Slide 1: RedHill Biopharma Corporate Presentation November 2016
RedHill Biopharma Ltd. (“RDHL”) Corporate Presentation November 2016 Filed Pursuantto Rule 433 of the SecuritiesActof1933 IssuerFreeWritingProspectusdated November1,2016 RegistrationNo.333-209702
Slide 2: Disclaimer and Forward Looking Statements
DisclaimerandForwardLookingStatements 2 Statementsinthispresentationthatarenothistoricalfacts(includingstatementscontaining"believes,""anticipates,""plans,""expects," "may,""will,""would,""intends,""estimates"andsimilarexpressions)areforward-lookingstatementswithinthemeaningoftheU.S. PrivateSecuriti
Slide 3: Offering and prospectus information
This presentation highlights basic information about RedHill Biopharma, Ltd. and the offering. RedHill Biopharma, Ltd. has filed a shelf registration statement on Form F-3 (Registration No. 333-209702) (including a base prospectus) with the U.S. Securities and Exchange Commission (the ?SEC?) which i
Slide 4: The Offering
RedHill Biopharma, Ltd. Listing: NASDAQ:“RDHL” TelAviv Stock Exchange:“RDHL” Size: ADSs representing[x] MillionShares (100% Primary) Option to Purchase Additional ADSs: 15% Use ofProceeds: Fund clinicaldevelopment programs, potential acquisitions, support commercial operations andgeneral corporate p
Slide 5: Robust Pipeline With Multiple Near-Term Milestones and Three Ongoing Phase III Programs
Robust Pipeline With Multiple Near-Term Milestones and Three Ongoing Phase III Programs • Potential blockbuster gastrointestinal drugs with three ongoing Phase III programs: • RHB-104 (Crohn’s): First Phase III study ongoing in the U.S., Canada, Europe, Israel, Australia and New Zealand • RHB-105 (H
Slide 6: Pipeline overview by drug and indication
Drug Planned Indication Pre-Clinical Phase I/II Phase III NDA/MAA G I & I n f l a m m a t i o n RHB-105 H. pylori infection RHB-104 Crohn’s disease Multiple sclerosis BEKINDA® (RHB-102) Gastroenteritis IBS-D Oncology support RHB-106 Bowel cleanser O n c o l o g y - G I / I n f l a m m a t i o n YELI
Slide 7: Multiple Near-Term Catalysts on the Horizon
Multiple Near-Term Catalysts on the Horizon 7 Q4 2016 RHB-104: • Safety-focused DSMB meeting for the MAP US Phase III study for Crohn’s disease • Top-line final results from the Phase IIastudy for multiple sclerosis Commercial asset: • Potential acquisition of certain commercial rights to GI asset c
Slide 8: Experienced Leadership Team
Experienced Leadership Team 8 DrorBen-Asher,CEO P.C.M.I. Ltd. AdiFrish, Senior VP Business Development & Licensing Y. Ben-Dror, MediGus Reza FathiPhD, Senior VP R&D XTL,PharmaGenics,Harvard Inst. of Chem. & Cell Biology Ira KalfusMD, Medical Director Lev Pharmaceuticals, Aetna/US Healthcare Terry F.
Slide 9: Experienced Leadership Team: Board and Advisors
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 FuriexPharmaceuticals, GSK Prof. ChezyBarenholz,PhD Prof., Hebrew University of Jerusalem, Co-inventor of Doxil® Mr. Abe
Slide 10: Financial Highlights
Financial Highlights* 10 RedHillBiopharma Ltd. Symbol (Exchange): NASDAQ:RDHL; TASE: RDHL Market Cap (approx.) $181.9 million Ordinary Shares Outstanding 127 million (Equivalentto 12.7 million ADSs traded on NASDAQ) Cash and Deposits as of September 30, 2016 (approx.) $40.5 million Cash and Deposits
Slide 11: RedHill's GI Focus: Treating Inflammatory Disease
RedHill’s GI Focus: Treating Inflammatory Disease “Where There is Inflammation –Look for Infection” 11 • The Emerging Microbiome Revolution: growing awareness that the microbiome plays a critical role in gastrointestinal illnesses • Lead products RHB-104 (Crohn’s disease) and RHB-105 (H. pylori) foc
Slide 12: RHB-104 Crohn's disease
RHB-104 Groundbreaking combination therapy targeting MAP bacteria for treatment of Crohn’s disease and potentially other autoimmune diseases First Phase III Ongoing in Crohn’s Disease Encouraging Top-Line Interim Results from Ongoing Phase IIaStudy in MS 12
Slide 13: The Link between Crohn's Disease and MAP
The Link between Crohn’s Disease and MAP 13 • MAP (mycobacterium aviumsubsp. 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 •
Slide 14: RHB-104 (Crohn's) - The Unmet Need
RHB-104 (Crohn’s) -The UnmetNeed • Existing drugs treat symptoms, are associated with numerous side effects and are widely considered to have limited efficacy in the long term • Significant failure rate with current standard of care -Remicade® Phase III trial * • 42% of enrolled patients in inflixim
Slide 15: RHB-104 (Crohn's) - First Phase III Ongoing
RHB-104 (Crohn’s) -First Phase III Ongoing With Potential Early Stop For Success in Q2/17 The Disease A severe inflammatory disease of the gastrointestinal tract with large unmet medical needs Planned Indication Treatment of Crohn’s disease in adult patients; Approved Orphan Drug Designation for ped
Slide 16: MAP US Phase III study design
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 Initiated September 30, 2013 Number of Subjects 410 Sites Up to 150
Slide 17: Phase II Study Demonstrates Healing of Mucosa in Crohn's Patients
BEFORE Deep colonic ulcers before therapy AFTER Healing, with scarring, after 20 months on therapy Recovered mucosa after 20 months on therapy AFTER BEFORE Extensive pseudo- polyps before therapy 17 A retrospective subset analysis of moderate Crohn’s disease patients; ** Data on file –T.J. Borody, M
Slide 18: Lancet reanalysis of Australian Phase III study
66% (67/102) p = .017 40% (41/102) p = .003 30% (31/102) p = .005 14% (16/111) 22% (24/111) 50% (55/111) 111 Placebo + prednisolone 102 Active + prednisolone Remission Endpoint Reanalysis Randomized denominator at time 0 66% (67/102) p = .017 39% (26/67) p = .054 24% (10/41) p = .14 43% (12/28) 56%
Slide 19: Australian Phase III Data Compared to Remicade
AustralianPhase III (Pfizer) Study Data Would Have Compared Favorably to Remicade® 39% (44/113) All subjects=23% (44/192) 28% (31/113) All subjects=16% (31/192) * Hanauer et al, (2002), The Lancet 359: 1541-1549. study similar to the reanalysis conducted by Behr and Hanley Remission at 54Weeks Remis
Slide 20: Phase IIa CEASE-MS study in multiple sclerosis
A Phase IIa Proof of Concept Study (the “CEASE-MS” study) to Assess the Efficacy and Safety of Fixed Dose Combination RHB-104 as Add-On Therapy to Interferon beta-1a in Patients Treated for Relapsing Remitting Multiple Sclerosis Initiated June 2013 Number of Subjects 18 Sites 2 sites in Israel Prima
Slide 21: CEASE-MS interim results
Interimresultsaftercompletionofthe24weektreatmentperiodofthestudy demonstratedpositivesafetyandefficacysignalsandsupportfurtherclinical developmentbasedonencouragingpreliminarydata: 1. Annualized relapse rate (ARR) at 24 weeks was 0.288 in the modified intent-to-treat (mITT) population and 0.0 in th
Slide 22: CEASE-MS interim results (continued)
* Cohen J A et al.: Oral Fingolimodor Intramuscular Interferon for Relapsing Remitting Multiple Sclerosis. NEJM. 2010, 362: 402-15 ** Cohen J A et al.: Alemtuzumabversus Interferon Beta 1a as First-Line Treatment for Patients with Relapsing-Remitting Multiple Sclerosis: a RandomisedControlled Phase
Slide 23: RHB-105 H. pylori
RHB-105 A new combination therapy for treatment of H. pylori infection -with QIDP designation, including Fast-Track development status Successful First Phase III Study Completed - Met Primary Endpoint with High Statistical Significance Preparations for Confirmatory Phase III Study 23
Slide 24: RHB-105 - First Line Treatment for H. pylori
RHB-105 -First Line Treatment for H. pylori Planned Indication First line treatment for eradication of H. pylori regardless of ulcer status Drug A novel combination of two antibiotics and a PPI (proton pump inhibitor): rifabutin, amoxicillin and omeprazole -in a single oral capsule Potential Advanta
Slide 25: H. pylori Infection - Progressive gastro-duodenal damage
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
Slide 26: Positive Phase III Top-Line Results
Positive Phase III Top-Line Results (June 2015) - Phase III study results demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105 (p< 0.001) - The study successfully met its protocol-defined primary endpoint of superiority over historical standard-of-care (SoC) efficacy levels of
Slide 27: ERADICATE Hp Phase III study design
A Randomized Placebo-controlled Phase III Study (“ERADICATE Hp”) to Assess the Safety and Efficacy of RHB-105 in the Treatment of Confirmed H. pylori Infection in Dyspepsia Patients, Regardless of Ulcer Status Number of Subjects 118 Sites 13 sites in the U.S. Duration of Study Treatment 14 days Prim
Slide 28: Phase II rifabutin rescue therapy study
• BorodyTJ et al. Efficacy and safety of rifabutin-containing ‘rescue therapy’ for resistant Helicobacter pylori infection. Aliment PharmacolTher.2006;23:481–488 The Phase II study was designed to test the efficacy of a triple therapy regimen combining rifabutin, pantoprazole and amoxicillin as resc
Slide 29: BEKINDA (RHB-102)
BEKINDA®(RHB-102) A bi-modal extended release, once-daily, ondansetron Ongoing U.S. Phase III for Gastroenteritis/Gastritis Ongoing U.S. Phase II study for IBS-D European MAA for Oncology Support Indications in discussions with regulatory authorities 29
Slide 30: BEKINDA: Gastroenteritis & Gastritis Phase III Ongoing
BEKINDA® (RHB-102): Gastroenteritis & Gastritis - Phase III Study Ongoing * Graves S. Nancy, Acute Gastroenteritis, Prim Care Clin Office Pract 40 (2013) 727–741 and Company analysis A Randomized, Double-Blind, Placebo Controlled, Parallel Group Phase III Study (“GUARD”) to Assess the Safety and Eff
Slide 31: BEKINDA: IBS-D Phase II Ongoing
BEKINDA® (RHB-102): IBS-D Phase II Study Ongoing 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 Drug Paten
Slide 32: YELIVA (ABC294640)
YELIVA™ (ABC294640) Phase II-stage first-in-class orally-administered sphingosine kinase-2 (SK2) inhibitor targeting multiple oncology, inflammatory and GI indications 32
Slide 33: YELIVA: The Drug, Market and Development Status
The Drug 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 Exclusive worldwide rights acquired from U.S.-based Apogee Biotech for all indications Extensive patent
Slide 34: Building a GI Specialty Pharma in the U.S. - Commercial Operations
Building a GI Specialty Pharma in the U.S. -Commercial Operations • RedHill is in the process for establishing commercial presence and capabilities in the U.S. • Commercial operations planned to support, among others, potential future commercial launch of RedHill’sGI-related products under developme
Slide 35: Robust Pipeline With Multiple Near-Term Milestones
Robust Pipeline With Multiple Near-Term Milestones and Three Ongoing Phase III Programs • Potential blockbuster gastrointestinal drugs with three ongoing Phase III programs: • RHB-104 (Crohn’s): First Phase III study ongoing in the U.S., Canada, Europe, Israel, Australia and New Zealand • RHB-105 (H
Slide 36: Thank You!
Thank You! RedHill Biopharma Ltd. 21 Ha’arba’a St. Tel-Aviv, 6473921Israel Email: info@redhillbio.com Web: www.redhillbio.com Tel: +972-3-541-3131 36
Slide 37: Pipeline overview by drug and indication
Drug Planned Indication Pre-Clinical Phase I/II Phase III NDA/MAA G I & I n f l a m m a t i o n RHB-105 H. pylori infection RHB-104 Crohn’s disease Multiple sclerosis BEKINDA® (RHB-102) Gastroenteritis IBS-D Oncology support RHB-106 Bowel cleanser O n c o l o g y - G I / I n f l a m m a t i o n YELI
Slide 38: Appendix
Rech. Biopharma Appendix
Slide 39: RHB-104 (Crohn's) - 80% Remission in Pediatric Study
RHB-104 (Crohn’s) -80% Remission in Pediatric Study Presented at ACG in October 2013 Background of study: Single site, retrospective study, conducted independently of RedHillby Professor Thomas Borody, MD in Australia; Results presented at ACG (American College of Gastroenterology) 2013 Annual Scien
Slide 40: RHB-104 (Crohn's) - Substantial Progress in Development
RHB-104 (Crohn’s) -Substantial Progress in Development • Improved formulation -all-in-one capsule • Acquired rights to several technologies and developing companion MAP diagnostic test with Q 2 Solutions (Quest Diagnostics) -successfully identified MAP DNA in blood samples from Crohn’s disease patie
Slide 41: RHB-104 - Multiple Barriers to Entry
RHB-104 -Multiple Barriers to Entry • Global patent strategy, including multiple formulations patents • 3 years (and potentially 5 years) data exclusivity • Potential PK synergies of APIs administered in the RHB-104 formulation that disappear when administered concomitantly • Lower concentrations of
Slide 42: RHB-104 (Multiple Sclerosis) - Success in Pre-Clinical Studies
RHB-104 (Multiple Sclerosis) - Success in 4 Pre-Clinical Studies Study No. 1 (Cytokine Concentrations) Significant reduction of pro-inflammatory cytokine concentrations of IL-6 and TNF, which are associated with inflammation and MS Study No. 2 (Prophylaxis) Significant reduction in the inflammatory
Slide 43: RHB-104 - Additional Potential Indications
RHB-104 -Additional Potential Indications RHB-104 (RA) RHB-104 (Lupus) RHB-104 (T1D) RHB-104 (Psoriasis) Planned Indication Treatment of Rheumatoid Arthritis (RA) Treatment of Systemic Lupus Erythematosus (SLE) Treatment of Type 1 Diabetes (T1D) Treatment of Psoriasis MarketSize 2013 WW market of ov
Slide 44: BEKINDA for Oncology Support
C o n c e n t r a t i o n ( n g / m L ) 0 50 100 150 C o n c e n t r a t i o n ( n g / m L ) 0 4 8 12 16 20 24 Time (h) Treatment-1 Treatment-2 Treatment-3 Day=1 BEKINDA® Zofran 8mg bid Zofran 24mg Day=1 Time (h) Planned Indication Prevention of chemotherapy and radiotherapy-induced nausea and vomit
Slide 45: BEKINDA (RHB-102) - Market Opportunity
BEKINDA® (RHB-102) -Market Opportunity 5-HT3 (serotonin) receptor antagonists are considered the most effective and significant class of drugs in prevention of nausea and vomiting Ondansetron: • The most prescribed first generation 5-HT3 inhibitor • Potentially attractive safety profile as indicated
Slide 46: YELIVA - Phase II-stage SK2 Inhibitor
YELIVA ™ • S1P promotes cancer growth and proliferation and pathological inflammation, including TNFa 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 t
Slide 47: Phase I Clinical Study of YELIVA in Advanced Solid Tumors
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
Slide 48: YELIVA - Successful Phase I Study Met Primary and Secondary Endpoints
YELIVA™ (ABC294640) -Successful Phase I Study Met Primary and Secondary Endpoints Final Results from the Phase I Study of YELIVA™ in Advanced Solid Tumors • The study successfully met its primary and secondary endpoints, providing key information about the drug’s safety, toxicities, PK and PD, suppo
Slide 49: YELIVA - Phase Ib/II Study for Multiple Myeloma
YELIVA™ (ABC294640) -Phase Ib/II Study for Multiple Myeloma Initiated Study Open-label, dose escalation Phase Ib/II study Site Duke University Medical Center Initiated September 2016 Number of subjects Up to 77 patients Lead Investigator Dr. YubinKang, MD, Associate Professor in the Division of Hema
Slide 50: YELIVA - Phase II Study for Hepatocellular Carcinoma
YELIVA™ (ABC294640) -Phase II Study for Hepatocellular Carcinoma Site Medical University of South Carolina (MUSC)and additional clinical sites Initiated October 2016 Number of subjects Up to 39 patients Lead Investigator Dr. Carolyn D. Britten, MD, Chief of the DivisionHematology/Oncology Division i
Slide 51: Diffuse Large B-Cell Lymphoma (DLBCL)
Diffuse Large B-Cell Lymphoma (DLBCL) APhaseI/IIstudytoevaluatethesafetyandtolerabilityofYELIVA™,aswellasprovidea preliminaryevaluationofefficacyofthedruginpatientswithrefractory/relapseddiffuselargeB- celllymphoma,primarilypatientswithHIV-relatedDLBCL Planned Indication Refractory/relapsed diffuse
Slide 52: YELIVA - Prostate Cancer NCI Grant for Pre-Clinical Studies
YELIVA™ * YELIVA™ -Prostate Cancer NCI Grant Awarded for Pre-Clinical Studies • Pre-clinical studies in vivo were conducted by scientists from Apogee Biotechnology Corp. and the Kimmel Cancer Center at Thomas Jefferson University with YELIVA™ in early stage and advanced prostate cancer models * • Th
Slide 53: RHB-106 Bowel preparation capsule
RHB-106 Bowel preparation capsule Out-licensed to Salix Pharmaceuticals 53
Slide 54: RHB-106 (Bowel Preparation) - Licensed to Salix
RHB-106 (Bowel Preparation) - Licensed to Salix Pharmaceuticals Planned Indication Preparation of the Gastrointestinal (GI) tract for GI procedures/surgeries (such as colonoscopy) Drug Patent-protected encapsulated formulation for bowel preparation Potential Advantages Improved safety over existing
Slide 55: MESUPRON & RP101
MESUPRON & RP101 Phase II-stage first-in-class small molecules targeting multiple oncology indications 55
Slide 56: MESUPRON: Planned Indication, Drug and Market
Planned Indication Gastrointestinal and other solid tumor cancers including locally advanced non-metastatic pancreatic cancer Drug A proprietary, first-in-class, urokinase-type plasminogen activator (uPA) inhibitor administered by oral capsule Potential Advantages Non-cytotoxic -established safety a
Slide 57: MESUPRON: first-in-class uPA inhibitor
• A first-in-class orally administered small molecule inhibiting tumor metastasis and growth • Exclusive worldwide* rights acquired from Wilex AG for all indications • MESUPRON inhibits the urokinase-type plasminogen activator (uPA) system, which has been shown to play a key role in tumor cell growt
Slide 58: MESUPRON - Clinical Development to Date
MESUPRON -Clinical Development to Date WX-UK1 IV Administration Total N=160 subjects (patients & healthy volunteers) Safety (single agent, Capecitabine combination) Tissue & Serum Pharmacokinetics Phase II Breast Cancer Combination study Capecitabine Phase Il Pancreatic Cancer Combination study Gemc
Slide 59: MESUPRON - Prior Phase II Clinical Studies
MESUPRON -PriorPhase II Clinical Studies Study Non-powered Phase II proof of concept study in pancreatic cancer Primary Endpoints Overall response rate; Progression free survival; Time to first metastasis; Overall survival Number of subjects 95 Treatment Mesupron200 mg/day or 400 mg/day together wit
Slide 60: RP101 - First-In-Class Phase II-stage Hsp27 Inhibitor
RP101 -First-In-Class Phase II-stage Hsp27 Inhibitor for Pancreatic Cancer • RedHill acquired exclusive option to purchase RP101 and next generation compounds from RESprotectGmbH • RP101 is a propriety, first-in-class, heat shock protein 27 (Hsp27) inhibitor, administered orally, which may prevent t
Slide 61: RIZAPORT Oral Thin-Film Rizatriptan
RIZAPORT® Oral Thin-Film Rizatriptanfor Acute Migraines European MAA Approved Under the European Decentralized Procedure; U.S. NDA Submitted 61
Slide 62: RIZAPORT (RHB-103) for Migraines - European MAA Approved, NDA filed
RIZAPORT® (RHB-103) for Migraines - European MAA Approved, NDA filed Planned Indication Migraine -one of the most common neurologic episodes Drug Patent-protected, oral thin film formulation of rizatriptan Potential Advantages Effective route of administration -advantageous for patients suffering fr
Slide 63: RIZAPORT - Commercial Triptan Market Opportunity
RIZAPORT ® (RHB-103) for Migraines - Commercial Triptan Market Opportunity * EvaluatePharma, 2013, WW annual sales by indication, migraine • RIZAPORT ® likely to be the first thin film triptan to reach the U.S. market • Rizatriptan was selected as the drug to deliver via VersaFilm™ because it: 1. Ex
Slide 64: RHB-101 Once-Daily Carvedilol
RHB-101 Once-Daily Carvedilol for Hypertension & Congestive Heart Failure 64
Slide 65: RHB-101 (Cardio)
RHB-101 (Cardio) Planned Indication Congestive heart failure (CHF), hypertension (high blood pressure)* Drug Patent-protected, controlled release formulation of carvedilol (GSK’s brand name “Coreg®”) Potential Advantages Once-daily oral administration; Price; Reduced food affect; Reduced dose (less