First-in-Class Dimer Therapeutics to Bring Relief to Patients with Gastrointestinal Disorders

Transcription

1 First-in-Class Dimer Therapeutics to Bring Relief to Patients with Gastrointestinal Disorders BIO CEO & Investor Conference February 2018

2 Forward-Looking Statement This presentation contains forward-looking statements, which reflect our current views and expectations with respect to future outcomes or events. When used in this presentation, the words could, believe, anticipate, intend, estimate, expect, project and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain such identifying words. Because these statements are based on current estimates and assumptions, they are inherently subject to risks that could cause the actual outcomes to differ materially from what we currently expect. Examples of forward-looking statements contained in this presentation include: expectations regarding the outcome of our clinical trials, obtaining regulatory approvals and the timing of such approvals and our capital requirements. These forward-looking statements are subject to numerous risks and uncertainties, including, among others, the facts that we are substantially dependent on our ability to successfully develop and commercialize our products; the commercial adoption of our products and any other product candidates we develop will depend on the degree of their market acceptance; we have only limited assets and will need to raise additional capital before we can expect to generate revenue or become profitable; and we have never generated any revenue and may never be profitable. Forwardlooking statements in this presentation apply only as of the date made, and we undertake no obligation to update or revise any forward-looking statements to reflect subsequent events or circumstances. Not an Offer This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any securities. Confidentiality This presentation is strictly confidential. We request that you keep any information related thereto confidential and that you do not disclose any of such information to any other parties without our prior express written permission. 2

3 Investment Highlights First-in-Class Therapeutics Best-in-Class Therapeutics Robust Pipeline Resourced for Success Proprietary dimer platform technology NCE and NME dimer therapeutics Proven mechanisms of action Designed for superior efficacy and safety Portfolio of multiple patents issued, no royalties or milestone payments ORP-101, a peripherally-acting buprenorphine dimer for treating IBS-D Superior abdominal pain relief, GI motility control, and safety No risk of abuse, pancreatitis, or CNS effect ORP-105, an acetaminophen (APAP) dimer for pain Designed to replace opioids as a first-line pain therapy No risk of hepatotoxicity, abuse Dimer therapeutics pipeline allows additional opportunities Team with successful track record in drug development for GI disorders $39M Series A with NEA, Takeda Ventures, Pappas Capital, Relativity HC Funded through Phase 2 data for ORP-101 (1H20), IND for ORP-105 3

4 Leadership Team: Significant GI and Drug Development Experience Team Kenneth Widder, M.D. Executive Chairman/Director Nikhilesh Singh, Ph.D. CEO/Director Mark Sostek, M.D. Chief Medical Officer Gregory Beyer VP, Finance & Operations Background Former Chairman and CEO, Santarus Founder and Former CSO, Transcept Pharmaceuticals Former Therapeutic Area Clinical Leader, AstraZeneca Former Director of SEC Reporting, Novacea TRULANCE VIBERZI and its design are registered trademarks of Allergan Holdings Unlimited Company. Trulance is a trademark of Synergy Pharmaceuticals Inc. KERYDIN is a registered trademark of Anacor Pharmaceuticals, Inc. 4

5 First-in-Class Dimer Therapeutics, Proven MOA The Linker Unbreakable link (chemically and metabolically stable) Same receptor pharmacology as the parent Distribution profile is different from the parent Drug Linker Dimer 5

6 Robust Pipeline of Dimer Therapeutics ORP-101 ORP-105 ORP-102 ORP-103 Candidate Nomination IND Development IBS-D Metabolically-stable, peripheral partial μ opioid agonist receptor and κ opioid antagonist for treatment of IBS-D Phase 1 Phase 2 Pain Metabolically-stable, potent, non-opioid analgesic that targets acetaminophen receptors, does not form liver toxic NAPQI metabolite Opioid Bowel Disorder Metabolically stable, non-systemic full μ opioid antagonist designed to mitigate abdominal distress following chronic opioid use Gastroparesis Metabolically stable, modulator of intestinal serotonin and norepinephrine designed to address intestinal motility disorders NAPQI = N-acetyl-p-benzoquinone imine 6

7 ORP-101

8 >28M IBS-D Patients, Urgent Need for Better Treatments >28M with IBS-D Chronic, debilitating condition Abdominal pain due to visceral hypersensitivity (neuropathic) Frequent diarrhea Only 30% of patients consult a physician Approved Therapies: Limited Efficacy Significant Safety Concerns 60% Do Not Respond 10X 1 Significant Risk of Pancreatitis 1 10x risk of pancreatitis for patients on eluxadoline compared to the general population (AERS) 8

9 ORP-101: Potential to Safely Treat Motility and Abdominal Pain in IBS-D Patients Dual Receptor Partial μ agonism for motility control and κ antagonism for pain control Controls Abdominal Pain Potent anti-hyperalgesic No Pancreatitis Risk Avoids pancreatitis by relaxing sphincter of Oddi No Risk of Abuse Does not cross the blood brain barrier 9

10 Cumulative 2 Hour Pellets ORP-101: Control of Stool Frequency is Dose Dependent Rodent Stress-induced Diarrhea Model Human Therapeutic Dose Expected to be mg N = Dose (mg/kg) 10 Human Equivalent Dose = 250mg

11 Abdominal pain as % EMG activity ORP-101 Relieves Abdominal Pain in IBS-D Murine Models Neuropharmacology Acetic Acid Neonatal IBS-D Mouse Model Eluxadoline 50 mpk Vehicle ORP mpk p= p=0.03 Source: Paus R, Schmelz M, Bíró T, Steinhoff M. Frontiers in pruritus research: scratching the brain for more effective itch therapy. Journal of Clinical Investigation. 2006;116(5): doi: /jci Colorectal Balloon Distension Pressure (mmhg) Relieves Pain by Blocking Peripheral Dynorphin (Κ Agonist)

12 Gallbladder weight (mg) SoO (Common Duct) Pressure (% CFB) ORP-101: Relaxes Sphincter of Oddi, Mitigates Risk of Pancreatitis Sphincter of Oddi 200 Guinea Pig Manometry Study Eluxadoline 5 mpk IV Gallbladder Volume Study p = p = NS p = p=0.002 n= ORP mpk IV 5 0 Saline ORP mpk ELX 50 mpk Time after Infusion (Minutes) SoO=Sphincter of Oddi; % CFB=% change from baseline 12

13 Phase 1 Data: -1 ORP-101 Effectively Distributes across the -1.5 GI Tissue, Not across CNS -2 Individual Plasma 2h Concentrations 4h 6h 8h 12h Change 24h 48h in Pupillary 72h Diameter after Oral Dose (ng/ml) Time from Dose after Oral Dose (mm) mg 15 mg 50 mg 150 mg 400 mg 800 mg Time (hours) h 4h 6h 8h 12h 24h 48h 72h Time (hours) GI Distribution Maximizes ORP-101 s Therapeutic Potential Lack of CNS Effect Mitigates Risk of Abuse 13

14 ORP-105

15 Opioids & APAP - $10B Segment of Pain Market 100M+ Suffer Chronic Pain in U.S. 1 Opioids $7B Revenues 2 Acetaminophen $3B+ Revenues 3 Addiction & Overdose Deaths Hepatoxicity Major U.S. Crisis from Pain Treatment Category Sources: 1 Institute of Medicine of The National Academies 2 15 Annually in U.S. by 2021; Cowen November Annually in U.S. in 2016, 30% Tylenol; Cowen November 2017.

16 ORP-105: Best-in-class Pain Therapeutic Profile Addictive? No Efficacy vs. APAP? More potent 1 First-line alternative to opioids? Dose titration without liver failure? Hepatotoxic NAPQI formation? Possible Yes No 1 In rodent pain model 16

17 Vehicle Acetaminophen Morphine ORP mpk ORP mpk Vehicle Acetaminophen Morphine ORP mpk ORP mpk Licking time (seconds) Licking time (seconds) ORP-105: Improvement in Pain Similar to Morphine, Better than APAP 150 Nociceptive Phase (0-5 Min.) ***P< vs Vehicle Peak Inflammatory Phase (20-25 Min.) 250 ***P<0.0001, **P<0.001, *P<0.05 vs Vehicle *** *** *** ** *** * *** 0 0 Mouse Hind Paw Formalin Study (All Doses Given IP): Morphine 5 mpk, APAP 200 mpk and ORP mpk & 400 mpk 17

18 Liver Enzymes ORP-105: No Liver Toxicity, Potential to Increase Dose to Treat Pain HED=4gms ** **p<0.001, *p<0.05 vs. Vehicle Alanine aminotransferase, n=5 Aspartate aminotransferase, n= * Vehicle Acetaminophen 300 mpk Acetaminophen 400 mpk ORP mpk ORP mpk Potential to Increase Dose of ORP-105 for Superior Efficacy in Treating Pain HED = Human equivalent dose 18

19 Poised to Become Leading GI Therapeutics Company Leadership Lead Asset Platform & Pipeline Funding Experienced team GI drug development expertise Track record of drug approvals ORP-101, potential best-in-class therapy for IBS-D Proven MOA derisks molecule P1 data 2H18 P2 trial planned 2H18 Multi $B market opportunity for efficacious, safe therapy ORP-105 IND-enabling studies ongoing Robust pipeline with significant potential $39M Series A Interest from toptier institutional and strategic investors, partners 19 Movantik is a trademark of AztraZeneca. Viberzi is a trademark of Allergan

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