drug re-formulation - creating new business opportunities dr. alex nivorozhkin, chief operating...
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Drug Re-Formulation - Creating New Business
Opportunities
Dr. Alex Nivorozhkin, Chief Operating Officer
Amorsa Therapeutics Inc., USA
Pharmaceutics & Novel Drug Delivery Systems, March 16-18, 2015, Dubai www.amorsatx.com
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The Need in Pain ManagementA Potent Non-Opioid Without the Adverse Effects
It’s time for a change:• 16,000 deaths per year due to opioid overdoses• High potential for addiction• Disabling side effects• Tolerance development
Morphine has been the gold standard for treating
moderate-to-severe pain for nearly 200 years!
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Why Reformulate Existing Drugs?
• Extending life cycle of the product (IP issues) – salt formation, route of administration, proprietary delivery
• Improve patient compliance, frequency, ease of administration-depot formulations (CNS)
• Serve newly found therapeutics indications -adjusting dose, route of administration, delivery
• Improving poor intrinsic physico-chemical properties– Poor bioavailability (due to poor solubility and/or permeability)– TCI reports (2014) identified 30 recently launched drugs with
poor bioavailability– BCS Class IV oral drugs sales >$145 B
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How to Find and Validate a Good Idea?
• Talk to the DOCTORS- Unmet medical needs- Capitalize on something already used off-label- Incorporate new formulation into existing practices
• Make friends with IP LAWYERS- IP landscape complicated due to years of disclosures and patent activity- Formulation patents are almost always perceived “weaker” than composition of matter (new API)
• Set an alliance with PHARMACOLOGISTS– The interest jumps if you have in vivo data – Understanding animal models (efficacy)– Understanding toxicology aspects
• Introduce your idea to a BUSINESS PERSON– First pass on commercial potential– Interactions with potential investors
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Multistep Iterative Process, You’ll have to Adapt
U.S. Market for Opioid Analgesics - $8.3 Billion (2013)
Unmet Medical Need for Pain Management
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Unlocking Ketamine’s Potential
• Ketamine was approved as an anesthetic in 1970 • Recent studies have shown ketamine’s analgesic
and antidepressant effects but with undesirable side effects
• Majority of therapeutic benefits are due to the conversion of ketamine to norketamine
• Amorsa is developing proprietary formulations of novel ketamine analogs designed to:– Deliver the potency of ketamine with fewer adverse effects – Be administered as convenient oral formulations– Offer patients an effective alternative to opioids
“The medical community is missing out on one of the best pain drugs there is.” Director, Defense Center for Integrative Pain Management
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Ketamine Pharmacology Challenge
Oral ketamine solution in healthy volunteers
Human PK Data (3rd party results)
Amorsa Solutions•Steady, controlled release formulations designed to limit spikes and improve kinetics•Focus on Norketamine – an active metabolite of KTM-with 2.5x half-life•Selectively deuterated nor-KTM analogs further extend exposure by 50 % (overall ca. 4x vs. KTM)
Problems•Spikes in plasma concentration leading to psychomimetic side effects•Short exposure due to fast clearance
Target Efficacy & Safety Range
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Leadership Team & Business AdvisorsJoe BlanchardChief Executive Officer
• Leadership experience with several early-stage, venture-backed life science firms
• Aushon BioSystems, Altus Pharmaceuticals, Genencor, Akzo Nobel, Conoco/DuPont
Alex Nivorozhkin, PhDChief Operating Officer
• Expert in drug formulation technologies, synthetic & medicinal chemistry
• Boston BioCom, Massachusetts General Hospital, Inotek Pharmaceuticals, Epix Medical
Mike Palfreyman, DSc, PhDChief Scientific Officer
• Expert in neuropharmacology & NMDA receptor antagonists
• Forum Pharmaceuticals, Anadys Pharmaceuticals, Marion Merrell Dow, Psychiatric Genomics
Business Advisors:Lewis Geffen, Esq, Corporate Counsel (Co-Chair of Venture Capital & Emerging Companies Practice, Mintz Levin)
Jacob Weintraub, Esq, IP Counsel (Senior Counsel, JWIP, LLC)
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Scientific & Clinical Advisory Board
Michael Palfreyman, DSc, PhDCo-Chairman
• Chief Scientific Officer, Amorsa Therapeutics
Mihir Kamdar, MDCo-Chairman
• Director, Cancer Pain Clinic at MGH• Harvard Medical School Faculty
Christopher Gilligan, MD
• Chief of Pain Medicine, Beth Israel Deaconess Medical Center
Robert Lenox, MD • Professor of Pharmacology and Clinical Neurosciences, University of New England
• Former Global Head of CNS Drug Discovery, Sanofi Pharmaceuticals
Lt Col (Ret) John Gandy, MD
• Member Defense Health Board and Emergency Medicine Physician
• Retired Air Force Special Operations Command Emergency Medicine Physician 9
Novel Deuterated Ketamine Analogs
Proprietary Formulations
Safe & Effective NMDA Receptor
Antagonists
• Built on known pharmacology
• Expedited clinical path possible
• Novel analogs expected to deliver improved efficacy and/or safety
• Convenient oral tablets • Neuro-attenuating
features designed to limit side effects
• All FDA approved ingredients
• Expected efficacy without the adverse effects
• Pipeline of high value applications
Amorsa’s Drug Development Platform
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Formulation Effects on Drug Release
Prototypical tablets formulated with racemic
ketamine
Novel hydrogel formulations of ketamine showing varying release profiles (in vitro experiments) Steady release of therapeutically effective concentrations without toxic spikes
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Technology applies to ketamine, norketamine and derivatives including (S)-norketamine-d
In vitro data translates well into in vivo dog model
Pilot PK Dog Study Using Ketamine-ER24 Tablet Formulation
Validates our pathway for rapid optimization of future formulations
20 mg ketamine tablets
Obtained target plasma drug levels for 24 hours without concentration peaks
Confirms a strong in vitro/in vivo correlation
Target Efficacy & Safety Range
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Deuterated (S)-Norketamine Analogs
• Previously studied compound with well-characterized pharmacological activity
• Norketamine, the active metabolite of ketamine
• More attractive PK profile than ketamine
• S isomer has more potency than R
• Targeted modifications to create novel drug candidates
• Provides improved pharmacokinetic properties that enhance safety and efficacy
S-Norketamine
(S)-Norketamine-d
(S)-Norketamine
Deuterium Modification
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Preclinical Product Candidates
ProductCandidate
Product Description
Planned Target Indications
DSN-FA Fast acting formulation containing (S)-Norketamine-d
• Acute Trauma Pain• Mass Casualties, Burns
DSN-ER12
Extended release 12-hour tablet containing (S)-Norketamine-d
• Chronic Pain • Post-Surgical Pain• Refractory Cancer Pain
Developing both fast acting and extended release formulations
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3-Year Drug Development Plan
Year 1 Year 2 Year 3
AmorsaProduct Indication
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
DSN-FA (fast acting)
Acute Trauma Pain
Preclinical Phase 1a & 1b(healthy volunteers)
Phase 2(thru Year 4)
DSN-ER12(extended release)
Chronic PainPreclinical
DSN-FA(fast acting)
Treatment-Resistant
Depression
Phase 2
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Note: Plan does not assume Fast Track designation or modified 505(b)2 path –both are possible pending FDA review
Who Dares, Wins
