HEALEY ALS Platform Trial - Investigational Products Tested in the Trial CNM-Au8 February 4, 2021
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HEALEY ALS Platform Trial
Investigational Products Tested in the Trial
CNM-Au8
February 4, 2021
Merit Cudkowicz, MD Sabrina Paganoni, MD, PhD
Principal Investigator Co-Principal Investigator
2
Accelerating ALS Therapy Development
Traditional
Intervention
Disease Treatment A
Platform
Intervention
Disease Treatment A Treatment B Treatment C Treatment D
3
Perpetual Adaptive Trial
Randomization Ratio 3:1; Shared Placebo
Open Label Extension offered
Open Label
Extension
Regimen A Zilucoplan
Placebo Open Label
Regimen B Extension
3:1 Randomization Verdiperstat
Regimen within each
Screening Open Label
Assignment Regimen
Placebo
Extension
(n=160 for Regimen C CNM-Au8
each regimen) (n=120 for active drug; Open Label
Regimen n=40 for placebo)
Placebo
D Extension
Pridopidine
Placebo
Shared Placebo
Screening 24 weeks on study drug (active:placebo = 3:1)
4
Regimen Leads
James Berry, MD, MPH Nicholas Maragakis, MD
MGH, Boston, MA Johns Hopkins, Baltimore, MD
Regimen co-Lead Regimen co-Lead
Confidential
5
Overview | CNM-Au8 (Regimen C)
1. What It Is
2 . H o w It Works
7
3. Evidence Supporting Treatment of A L S
CLENE | Going forthe Gold
Bulk Gold Molecular N a n o c r ysta l l i n e G o l d
8
I n b u l k fo r m , g o l d i s i n e r t a n d W h e n g o l d i s m a d e i n t o t i ny
u n re a c t iv e . It re s is t s c o rro s io n n a n o c r y s ta ls , g o ld b e c o m e s h i g h l y
a n d d o e s n ’ t r u st a c t i v e a s a Nanocatalyst
CNM-Au8 | What is aNanocatalyst?
In a biological or chemical reaction,
Reactant A and Reactant B combine to make a totally new Product C
+ =
A B C
C ata l ys i s R a t e
A nanocatalyst is a ver y, v e r y sm all c ata l yst
that m a ke s s p e c i f i c b i o l o g i c a l re a c t i o ns g o
faster, s o that m o r e o f P r o d u c t C is p r o d u c e d
rapidl y
4
Data on File, Clene Nanomedicine.
ALS | Restoring Neuronal Energetic Loss Is Essential
A L S Neuronal Metabolic C N M - A u 8 catalys i s s u p p o r t s A L S Neuronal Metabolic
Failure cellular e n e r g y in neuro ns … Support
Dendritic ATP Dend ritic
R etrac tion Network
Glycolysis &
TCA Cycle Sup p ortive
Astrocyte
A c tivated C om p rom ised
Healthy
A stroc yte Axon
NAD+ C N M- A u 8 NADH Myelinated
Axon
1
0 Mitochondrial
ETC Complex
A trop hied
AT P Healthy
Muscle Muscle
… p ro v i d i n g the brain, spinal co rd , a n d
m o t o r n e u ro n s with m o re a c c e s s to
Impaired
Neuromuscular Junction ke y e n e rg y metabolites, i m p ro v i n g
m o t o r neuron health a n d survival
Vandoorne et al. A c ta Neuropathologica (2018) 135:489–509. Data on File, Clene Nanomedicine.
CNM-Au8 | ALS Neuroprotection in Human Neurons
Induced Pluripotent Stem Cell In Vitro Results – Motor Neuron Markers
Concentration (ng/mL)
CNM-Au8
Improves
ALS Motor
1
1
Neuron
Survival &
Neuron
Connections
Karen S. Ho et al. “Redox-enhancing nanocatalysis improves motor neuron survival in vitro and SOD1 mouse motor function and survival in vivo.” Presented at 30th International
Symposium on A L S / M N D 2019. December 4-6, 2019.CNM–Au8 | Treatment Results in ALS Neuroprotection
In Vivo SOD1 Congenic Mouse
CNM-Au8 Improves Healthspan CNM-Au8 Improves Lifespan
Neurological Score Kaplan-Meier Survival Curve
( T D I Rodent Scale) SOD1 G93A Mice
(Mean ± SEM)
1
2
Karen S. Ho et al. “Redox-enhancing nanocatalysis improves motor neuron survival in vitro and SOD1 mouse motor function and survival in vivo.”
Presented at 30th International Symposium on A L S / M N D 2019. December 4-6, 2019.CNM-Au8 | Clean Animal Toxicology Findings
All Studies Resulted in No Adverse Effect Level (NOAEL) a
Standard ICH M3(R2) Toxicology Program
G e n o to x ic ity Single Dose Max Fe a s i b l e C h r o n i c To x ic i t y
In Vitro & In Vivo To x ic o k i n e t ic s To x ic o k i n e t ic s Rodent
(Rodent) Canine Rodent (1-Wk, SQ) Rodent (6-Month)
1
Safety Multi-Dose Max Fe a s i b l e C h r o n i c To x ic i t y
3 Pharmacology To x ic o k i n e t ic s To x ic o k i n e t ic s Canine
CNS, CV, Renal Canine (7-Day) Canine (3-Wk) Canine (9-Month)
Do s e R a nge MTD High Dose
Finding To x i c o k i n e t i c s To x i c o k i n e t i c s
Rodent, Minipig Canine (4-Wk) Rodent (3-Wk)
a N OAEL = No Dose Limiting ToxicitiesObserved
Data on File, Clene Nanomedicine.CNM-Au8 | Well Tolerated Safety Profile
No Related SAEs or Related Study Discontinuations Across >75 Yrs. Cumulative Exposure
P h a s e 1F i rst In H u m a n S t u d y P h a s e 2 M S & Pa r k i n s o n ’s Phase 2 & 3 A L S
• Most frequent A d v e r s e Ev e n t s b y
System O rga n Class: Nervous/GI
- Nearly all were Grade 1severity U p to 4 8 - w e e k s ex p o s u re U p to 16-weeks ex p o s u re
(mild)
1
• N o serious T E A E s , T E A E s leading U p to 21-weeks ex p o s u re U p to 3 6 - w e e k s ex p o s u re
4 to discontinuation of treatment,
o r T E A E s c o n s i d e r e d s e v e r e , l i fe-
threatening, or resulting in d e at h
U p to 18-weeks ex p o s u re U p to 5 0 - w e e k s ex p o s u re
• N o dose responsive T E A E s
o b s e r v e d in S A D or M A D
Data on File, Clene Nanomedicine.THANK YOU | From All of Us at Clene
Your trial participation means the world to us …
… together we will discover treatments for
neurodegenerative diseases that help people with
ALS, and empower them to thrive
10C l e n e N a n o m e d i c i n e , Inc. HQ & Clinical Development 6550 S. Millrock Drive, Suite G 5 0 Salt Lake City, UT 84121 R&D and Manufacturing 5 0 0 Principio Parkway, Suite 4 0 0 North East, MD 21901 ©2020 Clene Nanomedicine, Inc.
For More Updates
• Weekly webinars
The idea of came from our Patient Advisory Committee: we are excited to be talking with you
on a weekly basis and take any questions you might have
• Find the schedule and registration links on our website
https://www.massgeneral.org/neurology/als/research/platform-trial-news/
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