Harnessing the power of precision medicine
to treat Alzheimer’s and ALS
April 2017
TSX listed: PMN.TO
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Forward looking statement: safe harbor
This slide deck may contain certain forward-looking information. Such
information involves known and unknown risks, uncertainties and other
factors that may cause actual results, performance or achievements to be
materially different from those implied by statements herein, and therefore
these statements should not be read as guarantees of future performance or
results. All forward-looking statements are based on the Company’s current
beliefs as well as assumptions made by and information currently available to
it as well as other factors. Readers are cautioned not to place undue reliance
on these forward-looking statements, which speak only as of the date of this
slide deck. Due to risks and uncertainties, including the risks and
uncertainties identified by the Company in its public securities filings, actual
events may differ materially from current expectations. The Company
disclaims any intention or obligation to update or revise any forward-looking
statements, whether as a result of new information, future events or
otherwise.
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ProMIS Neurosciences Overview
— “Best in class” disease modifying therapies, selectively
targeting the root cause of AD
— Monoclonal antibodies targeting toxic oligomer variants
of A-beta, Tau and TDP43
— Precision/personalization – companion diagnostics to
identify different strains of A-beta toxic oligomer, target
right patients
— Publicly traded on the TSX (Toronto Stock Exchange)
Ticker PMN.TO
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Strong Foundation for ProMIS Strategy
Portfolio of mAb Therapies
Oligomer targeted; Companion Dx
“Best in Class” Disease Modifying
Therapies
ProMIS Technology Platform: the “Slingshot”
Rational Drug Design for Mabs, identifying
Disease Specific Epitopes
“BEST IN CLASS” PLAYBOOK:
Lipitor
$12BB
Humira
$16BB
Solvadi
$25BB
Toxic Oligomer Mab in AD
$??? BB
ALZHEIMER’S MARKET:
The toxic oligomer (A-beta, Tau) is the disease driver
Different strains require Personalized Medicine
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ProMIS is following the “best in class” playbook building the “Pharmasset of Alzheimer’s”
— The three largest products in industry history were not “first in
class”, but ”best in class”
- Solvaldi/Harvoni, Humira, Lipitor
— They evaluated predecessor compounds and executed scientific
strategies for creating meaningful improvements
— Pharmasett created Solvadi, best in class therapy in Hepatitis C,
and sold to Gilead after Ph2 data for $11BB
— ProMIS is creating the “Pharmasett of Alzheimer’s”, with clear
science based improvements over likely first in class therapy
Aducanumab from Biogen
— ProMIS competitive advantage lies in our platform technology,
patented processes that allow us to identify Disease Specific
Epitopes (targets for antibody drugs and diagnostics)
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Amyloid beta exists in multiple forms in the
brain – the prions or toxic oligomers are the neuron killers
The three forms of Aβ are monomer,
oligomers, and plaque
Monomer is created constantly in the
brain as Amyloid Precursor Protein
breaks down
Monomer always aggregates into
oligomers, which then may further
aggregate into fibrils and plaque
Sometimes oligomers take on a toxic
form = prions. Prions multiply rapidly
(propagate) by causing new monomer
(which is being created all the time) to
take on the same toxic form
nia.nih.gov
1Hardy & Higgins, 1992, Science; 2Citron M et al, 1992, Nature; 3Borchelt DR et al, 1996, Neuron; 4Podlisny MB et al, 1987, Science;
5Holtzman DM et al, 2012, Cold Spring Harb Perspec Med; 6Jonsson T et al, 2012, Nature; 7Meyer-Luehmann M et al, 2006, Science
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We now know that toxic Aβ oligomers, or
prions, not plaque, are the root cause of AD
— Aβ monomers and Aβ insoluble fibrils (plaque) have little or
no demonstrable toxicity in vitro or in vivo3-5
— Soluble Aβ oligomers show the highest degree of
neurotoxicity6
— Toxicity in primary neuron cultures and brain slices3,5,7-9
— Induction of cognitive impairment in rodents3,4
5min
6h
24h
24h control
Synaptotoxicity of
human Ab oligomers on
hippocampal neurons7
1Jacobsen
et al, PNAS 2006; 2Brier et al, Science Trans Med 2016; 3Shankar et al, Nature Med 2008;
et al,Nature Neuroscience 2005; 5Hong et al, Science 2016; 6Benilova et al, Nature Neuroscience
2012 - Review; 7Lacor et al, J Neuroscience 2007; 8Jin et al, PNAS 2011; 9Lauren et al, Nature 2009
4Cleary
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Clinical results confirm best in class TPP
Product
Clinical Results
Monomer
binding
Plaque
binding
Oligomer
binding
CDx
Aducanumab
(Biogen)
CTAD-2 yr. efficacy confirmed,
dose limiting ARIA-E
No
Yes
Yes
No
Solanezumab
(Eli Lilly)
CTAD- 11% efficacy; p=0.095,
3rd failed phase 3
Yes
No
Yes?
No
Verubecestat
Pivotal failed (interim futility)
N/A
N/A
No
(Merck BACE
inhibitor)
Depletes
Monomer
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Recent major clinical trial results reinforce
the science – the toxic oligomer is the target
— Products that bind monomer do not achieve approvable
efficacy – the monomer is a distraction
- Lilly’s Solanezumab, Merck’s BACE inhibitor
— Products that bind plaque cause a major, dose limiting side
effect – vascular edema, or brain swelling, also known as
ARIA-E
- This side effect limits the possible dose, and therefore
reduces potential efficacy
— Biogen’s Aducanumab works because it binds the “soluble
oligomer” (as Biogen describes it in their Nature journal
article); but it suffers ARIA-E that can be reduced but not
eliminated by dose titration
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Target product profile for “best in class” A-beta mAbs is
clear: a product meeting these criteria is likely to have better
clinical data than Aducanumab’s approved label
- NO MONOMER BINDING
- Monomer outnumbers oligomers
100 – 1000 fold
- Monomer binding reduces efficacy
through target distraction
- NO PLAQUE BINDING
-Target distraction reduces efficacy
- Plaque may be protective - sequester
- Plaque binding contributes to ARIA-E
- HIGHLY SELECTIVE TOXIC
OLIGOMER BINDING
- Targets root cause of neuronal death
- Must be highly selective to avoid
target distraction
- PERSONALIZED MEDICINE
WITH COMPANION DIAGNOSTIC
- Any single monoclonal antibody will
have non-responders due to different
toxic oligomer strains
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ProMIS is well on the way to completing the scientific
validation of a “best in class” portfolio in 2017
Bind
Oligomers
No
Monomer
binding
No plaque
binding
In Vitro
Neurotox
and prop
In Vivo
Neurotox
PMN310
✔
✔
✔
✔
✔
PMN320
✔
✔
✔
✔
PMN330
✔
✔
✔
PMN340
✔
✔
PMN350
✔
✔
Product
Lilly ‘s Solanezumab
failed three pivotal
trials due to
monomer binding
Prevalence
Cohort
Confirm
CSF and
blood
assay
Functional
Differentiation
ongoing
ongoing
ongoing
ongoing
ongoing
ongoing
ongoing
✔
ongoing
ongoing
ongoing
ongoing
✔
✔
ongoing
ongoing
ongoing
ongoing
✔
✔
ongoing
ongoing
ongoing
ongoing
Biogen’s Aducanumab
shows dose limiting side
effect (brain swelling)
due to plaque binding
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Administration of PMN310 to mice completely
prevents the loss of short-term memory formation
caused by toxic oligomers
Novel Object Recognition Assay
AbO +/- Mab
7 days
•
•
Control mice remember a familiar object when reexposed to it and spend more time exploring a new
object
Oligomer-injected mice lose the ability to
discriminate between known and novel objects and
spend equivalent amounts of time exploring both
Discrimination Index
0.6
0.5
*
*
0.4
0.3
0.2
0.1
#
0.0
-0.1
-0.2
Vehicle
AβO
PMN 310
+ vehicle
PMN 310
+ AβO
*different from AβO (p < 0.05) #different from vehicle (p <0.05)
Discrimination index = (Time exploring new object – time exploring familiar object) / total exploration time
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ProMIS “best in class” therapy: significant
progress & key catalysts on track for H1/H2 2017
— Further in vivo efficacy data on lead product PMN310
— Includes both behavioral and functional outcomes
— Comparative results versus aducanumab
— Further in vivo validation of other mAbs
— Cohort Study to assess prevalence of different strains of toxic
oligomers – underlining need for precision medicine
— Development of companion diagnostics
— Development of blood based screening assay
— Tau and TDP43: Identification & IP filings on specific epitope targets
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PMN 310 lead product: key steps in
development plan to clinical POC
Manufacturing scale-up
2018
GLP toxicology
2018
IND submission
Late 2018
Phase 1 single ascending dose trial
Phase 2 proof of concept trial
2019
Completion in 2021
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Numerous prior AD programs targeting A-beta
help set expectations for path forward…
GLP Tox
Manufacture
Ph 1 SAD
- Numerous previous
programs have had
success, few issues in
GLP tox,
manufacturing or
bioavailability
- High odds of success
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Ph 2 POC
- ProMIS plans a larger trial than Biogen
Aducanumab (n=166)
- With Companion Diagnostic (CDx) to
ensure correct oligomer strain
Expectations: better data than
Aducanumab
1) no ARIA-E due to no plaque binding,
IgG4 isotype
2) Higher efficacy – higher dose possible
3) Higher efficacy – CDx, no a priori
non-responders
ProMIS has successfully raised $7.7MM CDN in
four rounds, at increasing values, since a strategic
restart in July 2015
$25MM
Financial Status
$1.5MM
at
$24MM
Pre
$10MM
$2MM
$2.5MM at
$2MM Pre
“Restart”
July 2015
$2.7MM
at
$26MM
Pre
$1M
M at
$9M
M Pre
May
2016
201MM common shares
outstanding
~240MM including options
and warrants
Current burn rate ~$300k due
to efficient science process
Sep
2016
Feb
2017
Cash life into Q4 2017
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ProMIS has very experienced management
and outstanding advisory boards
Management
Advisory Board:
Gene Williams
- Executive Chairman
- Genzyme, DART, Adheris
Todd Golde Scientific Adv Bd (SAB)
- U. of Florida
Elliot Goldstein
- CEO
- Maxygen, DART, GSK
Lary Walker (SAB)
- Emory University
Neil Cashman
- Chief Science Officer
- Uinversity of British Columbia
Steven Plotkin
- Chief Physics Officer
- University of British Columbia
Johanne Kaplan
- Chief Development Officer
- Genzyme, GSK
Mara Aspinall Business Adv Bd (BAB)
- Ventana, Genzyme
Nigel Burns (BAB)
- CAT, SweetSpot
Michael Higgins (BAB)
- Ironwood, Genzyme, Voyager
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ProMIS Neurosciences: Summary
— Developing “Best in Class” disease modifying AD portfolio
— Numerous prior clinical programs have contributed to our understanding of
the “best in class” target product profile
- Selectively bind toxic oligomer (not monomer, not plaque)
- Personalize with companion diagnostics
— Multiple catalysts, value creation in 2017
— Lead program PMN310 on track for IND late 2018 & Phase 2 POC in 2021,
just after likely approval of “first in class therapy” Aducanumab
— PMN310 advantages over first in class therapy may lead to better clinical
data and significant value creation
- No side effect of brain swelling, ARIA-E
- Ability to dose higher increases efficacy
- Patient selection with companion diagnostic leaves out a priori nonresponders increases efficacy
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Contact
Eugene Williams, Executive Chairman
[email protected]
+1 (617) 460-0978
Elliot Goldstein, MD, CEO
[email protected]
+1 (415) 341-5783
Website:
www.promisneurosciences.com
Twitter:
https://twitter.com/ProMISinc
Linked In:
https://www.linkedin.com/company/promis-neurosciences
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