RedHill Biopharma Ltd.

Transcription

1 RedHill Biopharma Ltd. (NASDAQ: RDHL; TASE: RDHL) Presentation / January 2013

2 Disclaimer and Forward Looking Statements This presentation does not constitute an offer or solicitation to acquire and/or sell Company s shares and/or warrants or to participate in any investment in the Company. 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. These statements 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, unable to obtain FDA or other regulatory approvals for our products, unable to establish collaborations, or that our products will not be commercially viable, among other risks. 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. 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 Key Highlights An emerging Israeli biopharmaceutical company (NASDAQ: RDHL; TASE:RDHL) developing six patent protected drugs in late clinical stages: New formulations and combinations of existing drugs Reduced risks, time-to-market and costs RHB-104 in preparations for two Phase III efficacy trials in Crohn s, and a Phase IIa in Multiple Sclerosis RHB-105 in preparations for a Phase II/III efficacy trial in H. pylori 2 products (RHB-102 and RHB-103) successfully completed pivotal bioequivalence trials, and in preparations for U.S. New Drug Applications Strong balance sheet with no debt; sufficient funding to complete key development programs 3

4 Product Pipeline Drug Field Pre - Clinical Phase I/II Phase II/III Planned FDA filing* RHB-101 Cardio Under Review** RHB-102 Oncology Pivotal bioequivalence trial successfully completed 2013 RHB- 103 Migraine Pivotal bioequivalence trial successfully completed 2013 Complete N. America 2014 RHB-104 Crohn s Europe 2014 Next step Multiple Sclerosis Phase IIa Under Review RHB-105 H. pylori 2013/4 RHB-106 Gastro Prep RHB-107/8*** Analgesic /Decongestant Under Review 4 * Estimated timeline, subject to changes in development plans and/or regulatory (FDA) requirements including complementary and/or additional studies ** Regulatory path is under review RedHill is exploring regulatory path in the US and Europe *** Term sheet signed. Consummation of the transaction is subject to RedHill s due diligence and a definitive agreement

5 Leadership Management Team* Dror Ben-Asher, CEO P.C.M.I. Ltd., Harvard,Oxford Ori Shilo, Deputy CEO, Finance & Operations P.C.M.I. Ltd., Deloitte Israel Reza Fathi PhD, Senior VP R&D XTL,PharmaGenics,Harvard Inst. of Chem. & Cell Biology Ira Kalfus MD, Chief Medical Officer Lev Pharmaceuticals, Aetna/US Healthcare Gilead Raday, Senior VP Product & Corporate Development MSc Neurology, MBE Cambridge, Sepal Pharma Adi Frish, Senior VP Business Development & Licensing Essex Un., Y. Ben-Dror, MediGus Guy Goldberg, Chief Business Officer Eagle Pharma, ProQuest, Mckinsey, Yale, Harvard Tom Lang PhD, VP Clinical & Regulatory Affairs*** Serono US, Ciba-Geigy, Janssen, Warner-Lambert Board of Directors* Dan Suesskind Teva, VP Finance, Director Eric Swenden Alterphama nv, Lifeline Scientific Kenneth Reed MD Dermatologist; Director Minerva Biotechnologies Shmuel Cabilly PhD Scientist, Director in several life-science companies Dror Ben-Asher (see management) Ori Shilo (see management) Ofer Tsimchi** Danbar, Polysack, Director in several companies Alicia Rotbard** Director in several companies incl. Discount Bank, Kamada 5 Patrick Mclean, Product Manager Axcan Pharma, Giaconda Elkan Gamzu PhD, Product Manager *** Cambridge Neurosciences, XTL, Warner Lambert, Roche Clara Fehrmann, Product Manager Santhera Pharmaceuticals, Merck Canada, ICON Clinical Research * Personal background relates to selected former and current positions and education ** External Director *** Part time

6 Advisory Board* Jeff Leighton, PhD (Chairman, Advisory Board) Glaxo, Exogen, Genesis, Inspire, etc. Prof. Colin Blakemore PhD (Scientific) Oxford ; Past CEO, Medical Research Council, BTG Prof. Chezy Barenholz (PhD) Scientific) Head Laboratory of Membrane & Liposome R&D Hadassah (Jerusalem), Co-inventor of Doxil Werner Tschollar MD (Clinical and Regulatory) Past Senior VP for Worldwide R&D at Novartis Prof. Ran Oren, MD (Medical) Digestive and Liver expert Hadassa and The Hebrew University (Jerusalem) Prof. Thomas Borody MD (Medical) Founder, Centre for Digestive Diseases (Sydney); Mayo Clinic, inventor of RHB Joshua Schein PhD (Strategic) Past CEO and Co-founder Lev Pharma, Founder Depomed Inc. and Callisto Pharma Mr. Abe Shwartz (Strategic) Covalon Tech., CEO Cedara Software, Director Merge Healthcare Inc. Jerry Rosenblatt PhD (Marketing) IIBD Consulting, IMS Health, Professor of marketing Concordia University *Personal background relates to former and current positions and education 6

7 2012/2013 Recent and Upcoming Milestones Financing RHB-104 Successful completion of approximately $6.5 million private placement; Strong balance sheet with no debt; sufficient funding to complete key development programs Planned initiation of the first of two Phase III clinical trials in Crohn s - H Planned initiation of Phase IIa clinical trial in Multiple Sclerosis - January 2013 RHB-105 Planned initiation of Phase II/III clinical trial for treatment of H. pylori - Q RHB-103 Planned NDA filing Q1 2013, following successful completion of a pivotal bioequivalence trial with RHB an oral thin film formulation for treatment of acute migraine RHB-102 Planned NDA filing 2013, following successful completion of a pivotal bioequivalence trial with RHB-102 for the prevention of nausea and vomiting in cancer patients NASDAQ NASDAQ listing completed December 27 th 2012, through a Level II ADR (American Depository Receipt) facility; RedHill s NASDAQ and TASE ticker: RDHL 7

8 Where There is Inflammation, Look For Infection RHB-104 (Crohn s and MS) and RHB-105 (H. pylori) build on the success of Professor Thomas Borody, a leading innovator of therapeutic approaches to Gastrointestinal (GI) tract diseases and infections - RedHill s Advisory Board member, Professor Borody, developed the original triple therapy for peptic ulcer disease associated with H. pylori - RedHill is developing Professor Borody s two next generation combination GI therapies: RHB-104 and RHB-105 8

9 The Emerging Microbiome Revolution Growing awareness in the scientific community AND public at large about the microbiome as a critical SYSTEMIC actor The clinical possibilities of the microbiome is the most exciting and important work of my lifetime (scientist quoted in New Yorker, Oct. 2012) from obesity and diabetes, via heart disease, asthma and multiple sclerosis, to neurological conditions such as autism, the microbiome seems to play a crucial role (Economist, Aug. 2012) Looking at human beings as ecosystems that contain many collaborating and competing species could change the practice of medicine (Economist, Aug. 2012) 9

10 RHB-104 (Crohn s) The Disease Planned Indication Drug Crohn s a severe inflammatory disease in the gastrointestinal tract Treatment of Crohn s disease in adult patients In addition, Orphan Drug Designation for pediatric Patent protected combination of three antibiotic ingredients in a single capsule (clarithromycin, clofazimine and rifabutin) Potential Advantages Diagnostics Existing drugs only treat the symptoms and are widely considered of limited efficacy in the long term RedHill s diagnostic test for MAP (Mycobacterium Avium Paratuberculosis) detection is developed with Quest Diagnostics Market Size Worldwide market of $3 billion in 2011* Development Status Estimated Costs Several clinical trials were conducted, including two Phase II (2002 and 2005 respectively) and a Phase III (2007) in Australia ** Planned Phase III in North America and Israel (H1 2013), Phase III in Europe and other supplementary studies as part of the development program and regulatory strategy Total $13-14 million to complete a Phase III trial in North America and Israel and a Phase III trial in Europe 10 *EaluatePharma (2011) ** RHB-104 formulation includes certain improvements as compared to the drug used in the Australian trial

11 RHB-104 (Crohn s) The Unmet Need A welcome alternative for Crohn s patients Existing drugs treat symptoms 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 infliximab (Remicade ) Phase III trial failed to qualify as responders On intent-to-treat basis, only 23-26% in remission at 30 weeks Increasing number of safety issues reported to FDA for infliximab (Remicade )** Black box warning related to serious infections and malignancy Costs of current anti-tnfɑ drug treatments is approximately $18-30k / year *Hanauer at al (2002), Lancet Infectious Diseases 359: ** Moore et al (2007), Arch Intern Med 167:

12 Previous Phase III Study Design Flaws but Showed Promising Results (Retrospective Analysis) Phase III conducted by Pharmacia in Australia (2007) and focused on relapse as primary endpoint RHB-104*** Phase III Results Study failed to demonstrate efficacy in relapse but showed promising remission results compared** to Remicade *: Active Arm 213 Patients (100%) Placebo Arm Remicade 102 Active + prednisolone Weaned (100%) 111 Placebo + prednisolone Weaned (100%) 30 weeks 39% remission ITT = 23% Separate trials; Theoretical comparison only 16 weeks 66% remission p = weeks 50% remission 54 weeks ITT = 15% 52 weeks 42% remission p = weeks 25% remission weeks 33% remission p = weeks 18% remission *A leading drug for symptomatic treatment of Crohn s **The two studies ( RHB-104 and Remicade ) were conducted separately. See Behr and Hanley (2008), Lancet Infectious Diseases 8:344 ***RHB-104 formulation includes certain improvements as compared to the drug used in the Australian trial

13 Phase II Study Pictures in Crohn s Patients* Deep colonic ulcers Before therapy Healing, with scarring, after 20 months on therapy BEFORE AFTER Extensive pseudopolyps before therapy Recovered mucosa after 20 months on therapy 13 *Borody et al (2002), Digest Liver Dis 34:29-38

14 RHB-104 (Crohn s) Progress Since the Australian Phase III Study Improved formulation Acquired rights to, and developing MAP detection diagnostic test Obtained Orphan Drug status for pediatric usage Developed the patent estate Engaged with CRO and CMO Appointed Prof. David Graham as lead investigator for the North American study Amended the IND and in advanced preparations to initiate the first of two Phase III studies 14

15 RHB-104 (Multiple Sclerosis) Planned Indication Treatment of Relapsing Remitting Multiple Sclerosis (MS) Drug Patent protected combination of three antibiotic ingredients in a single capsule (clarithromycin, clofazimine and rifabutin) Potential Advantages Existing drugs symptomatic treatment Oral administration Market Size Worldwide market of over $8 billion* Development Status Performed 3 pre-clinical studies using MS EAE model Phase IIa in Israel planned to commence January *Datamonitor (2011) Market and Product Forecast MS

16 Mean Clinical Score +/- SEM RHB-104 Multiple Sclerosis Therapy Success in 3 pre-clinical studies toward a Phase IIa trial Pre-clinical results demonstrated efficacy: Study No. 1 (Cytokine concentrations ) Study No. 2 (Prophylaxis) Study No. 3 (Relapse) Significant reduction of pro-inflammatory cytokine concentrations of IL-6 and TNF, which are associated with inflammation and MS Significant reduction in the inflammatory area and level of demyelination Significant reduction of incidences of relapse EAE* severity (mean clinical score) vs. time** Average demyelination score** 4 Vehicle Demyelination (LFB staining) + SEM 3 RHB-104, 36 mg/kg, p.o., BID Day After Immunization Vehicle RHB-104, 36 mg/kg 16 * The three pre-clinical studies were conducted using the experimental autoimmune encephalomyelitis (EAE) MS model ** Selected charts from Study No. 2

17 RHB-105 (H. pylori) Planned Indication Drug H. pylori / Ulcers Patent protected combination of three known and approved substances (rifabutin, amoxicillin and omeprazole) Potential Advantages Potential to become the leading effective treatment Market Size U.S. market is estimated at approximately $1-1.5 billion* Development Status Phase IIa conducted (2005) in Australia Phase II/III planned to commence Q Estimated Cost $2 million to complete Phase II/III 17 *Approximately three million H. pylori infected patients are treated per annum in the U.S. (Colin W. Howden, MD, et. Al (2007), The American Journal of Managed Care). Market size is estimated by the Company based on the above and the price of current treatments

18 RHB-105 (H. pylori) H. pylori bacteria has critical role in gastritis, peptic ulcer and gastric cancer Standard therapy fails in up to 30-40% of patients who remain H. pylori positive Growing resistance of H. pylori to clarithromycin and metronidazole RHB-105 is a novel combination of two antibiotics and a PPI: rifabutin, amoxicillin and omeprazole Phase II study demonstrated over 90% eradication in 130 patients who had previously failed standard therapy* *Borody et al (2005), Ailment Pharmacol Ther 23:

19 RHB-102 (Oncology Support Nausea & Vomiting) Planned Indication Drug Prevention of chemotherapy and radiotherapy induced nausea and vomiting Patent protected, once-daily controlled release tablet formulation of ondansetron (GSK s brand name Zofran ) Potential Advantages Allows once-daily oral administration during radiation therapy treatment Market Size Worldwide market for serotonin (5-HT3 ) receptor is estimated at $1 billion* Development Status Pilot clinical trial conducted Successfully completed pivotal bioequivalence clinical trial Planned NDA filing *BCC Research (2010). RHB-102 belongs to the family of 5-HT3 serotonin receptor inhibitors

20 ln(concentration) RHB-102 (once-daily formulation of the antiemetic ondansetron) Successfully completed pivotal bioequivalence clinical trial Pharmacokinetic comparison between GSK s Zofran and RHB LOGARITHMIC PROFILE OF THE MEAN Time (hours) RHB-102 TEST 2 Zofran 8mg REFERENCE Trial results: 20 Bioequivalence Fast Onset Low Coefficient of Variance

21 RHB-103 (Migraine) Planned Indication Migraine one of the most common neurologic episodes Drug Patent protected, oral thin film formulation of rizatriptan Potential Advantages Market Size Development Status Ease of use; Discrete; No need to swallow water Worldwide triptan market for the treatment of migraine exceeds $2 billion* Pilot clinical trial conducted Successfully completed a pivotal bioequivalence trial NDA filing planned Q Acquired from IntelGenx Corp. Co-development agreement in place 21 *Business Insights report (2011)

22 RHB-103 (oral thin film of the migraine drug rizatriptan) Successfully completed pivotal bioequivalence clinical trial Pharmacokinetic comparison between Merck s Maxalt MLT and RHB-103 Trial results: 22 Bioequivalence Fast Onset Low Coefficient of Variance

23 RHB-106 (Gastrointestinal Preparation) 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 No need to consume liquid solution; No bad taste Potential Market Size Worldwide potential market is estimated at approximately $1.4 billion* Development Status Phase IIa conducted in 62 patients (2005) in Australia** 23 *EvaluatePharma (2012) ** Borody et al (2006), Journal of Gastr and Hepat, 21: 87-88

24 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 Potential Market Size Worldwide potential target market of $500 million* Several clinical trials were conducted Development Status Examination of regulatory path in the US and Europe on the basis of existing clinical data 24 *Sales data from Scrip Intelligence (2012); GlaxoSmithKlinet annual report (2011) ; IMS Health sales data for carvedilol (2011)

25 Financial Highlights nine months period ended Sept. 30, 2012 December Successful completion of approximately $6.5 million private placement, following which RedHill s cash balance will be approximately $19 million Balance Sheet (USD, in millions) Operational Results* (USD, in millions) Cash and cash equivalent (additional $6.5 million was raised in December 2012) 13.7 R&D costs 5.2 Total assets 15.3 G&A costs 1.7 Liabilities** 1.8 Operating loss 6.9 Equity 13.5 Net cash - used for operating activities * For the nine months period ended September 30, 2012 ** Primarily due to potential future royalty liabilities to Company investors. The royalties are revenue-based and will only be paid subject to certain future revenues actually being generated

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