Download Dr. Alex Nivorozhkin, Chief Operating Officer Amorsa Therapeutics

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 Management
A Potent Non-Opioid Without the Adverse Effects
Morphine has been the gold standard for treating
moderate-to-severe pain for nearly 200 years!
It’s time for a change:
• 16,000 deaths per year due
to opioid overdoses
• High potential for addiction
• Disabling side effects
• Tolerance development
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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?
Multistep Iterative Process, You’ll have to Adapt
•
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)
–
•
CMC
PK/Tox
IP
Understanding toxicology aspects
Introduce your idea to a BUSINESS PERSON
–
–
First pass on commercial potential
Interactions with potential investors
Docs
BD
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Unmet Medical Need for Pain Management
U.S. Market for Opioid Analgesics - $8.3 Billion (2013)
Post-Trauma
Pain
• Opioids are associated with serious side
effects including respiratory depression
• Military priority for non-opioid treatments
Post-Operative
Pain
• 70 million surgeries each year in the U.S.
• >50% report moderate to severe pain
Refractory
Cancer Pain
• Up to 25% of advanced cancer patients
have refractory pain – nothing works
• No FDA approved treatment for patients
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Unlocking Ketamine’s Potential
“The medical community is missing out on one of the best pain
drugs there is.” Director, Defense Center for Integrative Pain Management
• 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
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Ketamine Pharmacology Challenge
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)
300
Dose 50 mg
Cmax 280 ng/mL
Tmax 1.1-1.6 h
T1/2 1.1-5.3 h
200
Target Efficacy &
Safety Range
ng/mL
Problems
• Spikes in plasma concentration leading
to psychomimetic side effects
• Short exposure due to fast clearance
100
0
0
2
4
6
Hours
8
10
12
Oral ketamine solution in healthy volunteers
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Leadership Team & Business Advisors
Joe Blanchard
Chief Executive Officer
• Leadership experience with several early-stage,
venture-backed life science firms
• Aushon BioSystems, Altus Pharmaceuticals,
Genencor, Akzo Nobel, Conoco/DuPont
Alex Nivorozhkin, PhD
Chief Operating Officer
• Expert in drug formulation technologies, synthetic
& medicinal chemistry
• Boston BioCom, Massachusetts General Hospital,
Inotek Pharmaceuticals, Epix Medical
Mike Palfreyman, DSc, PhD
Chief 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, PhD
Co-Chairman
•
Chief Scientific Officer, Amorsa Therapeutics
Mihir Kamdar, MD
Co-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
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Amorsa’s Drug Development Platform
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
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Formulation Effects on Drug Release
Novel hydrogel formulations of
ketamine showing varying release
profiles (in vitro experiments)
100
K-ER8
80
Release, %
Steady release of therapeutically
effective concentrations without
toxic spikes
Established Prototype
Formulations
K-ER12
60
K-ER24
40
20
In vitro data translates well into in
vivo dog model
Technology applies to ketamine,
norketamine and derivatives
including (S)-norketamine-d
0
0
5
10
15
20
25
30
Time, h
Prototypical tablets formulated with
racemic ketamine
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Pilot PK Dog Study Using Ketamine-ER24
Tablet Formulation
Obtained target plasma drug levels for
24 hours without concentration peaks
200
Target Efficacy &
Safety Range
ng/mL
Confirms a strong in vitro/in vivo
correlation
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Validates our pathway for rapid
optimization of future formulations
0
0
5
10 Hours 15
20
25
20 mg ketamine tablets
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Deuterated (S)-Norketamine Analogs
(S)-Norketamine
• Previously studied compound with wellcharacterized pharmacological activity
• Norketamine, the active metabolite of ketamine
• More attractive PK profile than ketamine
• S isomer has more potency than R
S-Norketamine
Deuterium Modification
• Targeted modifications to create novel drug
candidates
• Provides improved pharmacokinetic properties
that enhance safety and efficacy
(S)-Norketamine-d
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Preclinical Product Candidates
Developing both fast acting and extended release formulations
Product
Product
Candidate 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
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3-Year Drug Development Plan
Year 1
Amorsa
Product
DSN-FA
(fast acting)
DSN-ER12
(extended release)
DSN-FA
(fast acting)
Indication
Acute
Trauma Pain
Chronic Pain
Treatment-Resistant
Depression
Q1
Q2
Q3
Year 2
Q4
Preclinical
Q1
Q2
Q3
Year 3
Q4
Q1
Q2
Q3
Q4
Phase 1a & 1b
Phase 2
(healthy volunteers)
(thru Year 4)
Preclinical
Phase 2
Note: Plan does not assume Fast Track designation or modified 505(b)2 path –
both are possible pending FDA review
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Who Dares, Wins
Contacts:
Alex Nivorozhkin, Ph.D.
Chief Operating Officer
(617) 921-0114
[email protected]
www.amorsatx.com
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