Serina Therapeutics, Inc. · AMEX:SER
Serina Therapeutics — 2nd Neuroscience Innovation Forum 2019
27 slides from Serina Therapeutics's conference presentation, Jan 6, 2019
Slide 1: POZ – The Era of Once Weekly Continuous Drug Delivery in Parkinson's Disease is Here
POZ – The Era of Once Weekly TM Continuous Drug Delivery in Parkinson’s Disease is Here Randall W. Moreadith, MD, PhD President and CEO 2nd Neuroscience Innovation Forum January 6th 2019 2019
Slide 2: Unparalleled track record in polymer therapeutics
Unparalleled track record in polymer therapeutics Serina Founders and Management Milton Harris and Michael Bentley developed first generation PEGs at Shearwater Polymers Acquired by Inhale Therapeutics in 2001 (Nektar) Licensed for research and therapeutic applications (multiple products today
Slide 3: Polymers are very effective at providing half-life extension of proteins
“Polymers are very effective at providing half-life extension of proteins – why not small molecules ?” The universe of small molecules for half-life extension is vastly larger than proteins – but that required the development of a polymer technology for programmed drug release. 2019
Slide 4: The Pipeline
The Pipeline Drug Candidate Indication Research Preclinical Phase I Phase II Phase III SER-214 Parkinson’s disease (rotigotine) SER-214 Restless Legs (rotigotine) Syndrome SER-240 Parkinson’s disease (apomorphine) OFF time reduction SER-227 Post-operative pain (buprenorphine) Opioid abuse SER-228/22
Slide 5: Chemical Structures of Pipeline Compounds
Chemical Structures of Pipeline Compounds All have an accessible chemical handle Buprenorphine Immunotherapy Rotigotine Apomorphine Cannabidiol Tetrahydrocanabinol CBD THC • Candidate small molecules must have a “chemical handle” • Linkers are attached to the –OH, with an azide moiety at the other e
Slide 6: How we make POZ for small molecules
How we make POZ for small molecules Immunotherapy • Programmable loading of polymer is determined by the ratio of pentynyl : neutral monomers at initial synthesis (example above is a 20 kDa 10 pendent POZ) • Reproducible “one pot” synthesis of polymers from 5-100 kDa • Single-step purification - IEC
Slide 7: POZ-therapeutics – One step "click" chemistry
POZ-therapeutics – One step “click” chemistry Immunotherapy * We have a “toolkit” of ~ 20 linkers Ester linkage is stable until conjugate ready for attachment to -OH is cleaved in the blood • Controlled drug loading at the “click chemistry” step; stable API (> 3 years); Global exclusive license to “
Slide 8: The Challenge – Provide Continuous Drug Delivery
The Challenge – Provide Continuous Drug Delivery None of the existing oral drugs for PD provide continuous drug delivery Immunotherapy Weekly SC Injection Therapeutic Dose Range “ON” with Dyskinesia Good “ON” Time Generally Unpredictable “OFF” Wearing “ON-OFF” Time Dose Off Morning off Failure Parti
Slide 9: A Weekly SC Injection of POZ-rotigotine (SER-214) Provides Continuous Drug Delivery in Monkeys
A Weekly SC Injection of POZ-rotigotine (SER-214) Provides Continuous Drug Delivery in Monkeys Plasma levels of Released Rotigotine following weekly SC injections of SER-214 to Normal Monkeys Immunotherapy 7.0 mg/kg dose (male and fe male ; n=10, SD) 100 Plasma concentration (ng/mL) 10 1 week 1 we
Slide 10: SER-214 Advanced into Phase Ia in Stably-treated Parkinson's Patients
SER-214 Advanced into Phase Ia in Stably-treated Parkinson’s Patients Asses safety, tolerability and pharmacokinetics Cohort Dose of SER-214 (SC) Data Establish safety and tolerability of a Collected weekly injection of SER-214 in Parkinson’s Disease patients Safety endpoints will establish if a
Slide 11: A Weekly SC Injection of SER-214 in Parkinson's Patients Provides Continuous Drug Delivery
A Weekly SC Injection of SER-214 in Parkinson’s Patients Provides Continuous Drug Delivery Immunothera py • Data from Cohort 3 in the multiple dose portion of the Phase Ia trial in Parkinson’s disease patients • Patients received: an initial subcutaneous dose of 50 mg SER-214; 100 mg dose in Week 2;
Slide 12: A Weekly SC Injection of SER-214 Improves Motor Scores
A Weekly SC Injection of SER-214 Improves Motor Scores Dose-dependent Decline in UPDRS (Part III) Effect of dose on UPDRS part III scores in Parkinson's patients following weekly sc of SER-214 Immunotherapy (mean for n=5) 2 Dose of SER-214 (mg) 100 200 300 400 UPDRS change from pre-dose 0 -2 -4 2 -6
Slide 13: SER-214 Summary
SER-214 Summary A single weekly subcutaneous injection of SER-214 provides continuous drug delivery for Parkinson’s disease and RLS patients Immunotherapy • Entering Phase Ib in Parkinson’s disease in 2019 (PD – device to deliver a single weekly ~ 5 mL injection over ~ 10-15 minutes) • In early PD u
Slide 14: POZ-apomorphine
POZ-apomorphine Apomorphine has many of the characteristics ideal for POZ • Apomorphine Most potent dopamine agonist known (our KOLs call it the “holy grail” of dopamine Rx) Reverses akinesia within minutes Limited bioavailability makes it unsuitable as an oral drug Short half-life of < 30 m
Slide 15: APO-Go - Apomorphine
APO-Go - Apomorphine Apomorphine works in advanced PD … current formulation has significant adverse reactions Patients with advanced PD have > 6 hours a day of “off” time where they are unable to perform routine daily tasks1 Severe skin reactions Patients use an infusion device to provide continuous
Slide 16: TOLEDO
TOLEDO 1 Treatment effect in “off” time reduction was immediate and sustained on therapy 1 TOLEDO (Published July 2018) – The only RCT of apomorphine vs placebo. Advanced PD patients received a daily SC infusion of placebo or APO-Go; the primary endpoint was change from baseline in total daily “off”
Slide 17: POZ-apomorphine (SER-240 and SER-241 - differ by linker)
POZ-apomorphine (SER-240 and SER-241 - differ by linker) Designed to provide programmable drug release … H y d r o ly s is o f P O Z 2 0 K 1 0 p D ie s t e r f ie d A p o m o r p h in e in H u m a n P la s m a a t 3 7 C 100 90 SER-240 80 SER-241 The ability to program N o r m a liz e d R e le a s
Slide 18: APO-Go vs POZ-apomorphine
APO-Go vs POZ-apomorphine … will a POZ-conjugate avoid the development of skin issues ? Single dose study in monkey of infusion of APO-Go versus SER-240 versus SER-241 Group I : 12 hour infusion of 1% Apo-Go solution (dose equivalent to human equivalent dose of ~ 1.5 mg / kg) End of infusion Dai
Slide 19: Group I - APO-Go
Group I - APO-Go No skin reactions at end of infusion At 12 hours there were no skin reactions other than slight redness at site on infusion Non-confidential 1
Slide 20: Group I - APO-Go
Group I - APO-Go Significant skin reactions – abscess formation in the APO-Go group At 72-96 hours there were draining abscesses at site of infusion in all monkeys in the APO-Go group Non-confidential 2
Slide 21: Group 3 – POZ-apomorphine (SER-241)
Group 3 – POZ-apomorphine (SER-241) No skin reactions following injection 1 From 12-120 hours there were no skin reactions in any Group 2 or Group 3 animals 1 Biopsy of the injection site revealed no evidence of inflammation Confidential 2
Slide 22: POZ-apomorphine vs APO-Go infusion
POZ-apomorphine vs APO-Go infusion POZ-apomorphine conjugates – provide continuous drug delivery for ~ 7 days P K P r o file o f R e le a s e d A p o m o r p h in e a fte r S C d o s in g o f A p o m o r p h in e , S E R -2 4 0 a n d S E R -2 4 1 in F e m a le M o n k e y s APO-Go was ( 1 .5 m g /k
Slide 23: Human Modeling
Human Modeling Multi-dose PK of SER-241 simulated from monkey PK Monkey PK of SER-241 was modeled using a 1- compartment fit to predict human PK 1 A weekly dose of ~ 0.5-2 mg eq/kg SER-241 is predicted to yield plasma levels ~ 10 ng/mL free apomorphine 2 This would require a device to deliver betwee
Slide 24: Enable Injections
Enable Injections Injection systems designed for ease of use, compliance, and avoidance of needle injury Automatic Reconstitution system for liquid/powder Uniform mixing Minimal input from user (simply attach vials) Does not need a healthcare provider to administer Avoids exposure to needle injury C
Slide 25: Enable Injections
Enable Injections Injection systems designed for ease of use, compliance, and avoidance of needle injury Remove device from filling system Adhesive is exposed automatically Press onto clean skin area Press button, infusion begins automatically Device retracts needle when infusion is complete, button
Slide 26: Summary
Summary Once weekly continuous drug delivery with a convenient, patient-compliant approach – a long sought clinical strategy - is here Immunotherapy • POZ-rotigotine (SER-214) is poised to enter Phase Ib in 2019 • 505(b)(2) regulatory pathway; indicated for early PD • A single weekly SC injection pr
Slide 27: Thank You
Thank You
Serina Therapeutics — 2nd Neuroscience Innovation Forum 2019 on 6ix