ProMIS Neurosciences Inc. · NASDAQ:PMN
ProMIS Neurosciences — Investor Presentation (January 2020)
53 slides from ProMIS Neurosciences's investor presentation, January 2020
Slide 1: ProMIS Neurosciences: Best in Class therapy for misfolded protein diseases
ProMIS Neurosciences: “Best in Class” therapy for misfolded protein diseases, based on a proprietary discovery platform Toronto Stock Exchange (TSX) ticker: PMN January 2020 OTCQB ticker: ARFXF 1
Slide 2: Forward looking statement: safe harbor
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 state
Slide 3: ProMIS Neurosciences Overview
ProMIS Neurosciences Overview • Growing portfolio of monoclonal antibody candidates focused on neurodegenerative and other mis-folded protein diseases • Lead program PMN310: scientific superiority over Biogen’s aducanumab, first disease modifying therapy in AD with positive phase 3 data - PMN310 sel
Slide 4: Neurodegenerative diseases: in need of disease modifying therapy
Neurodegenerative diseases: in need of disease modifying therapy attacking the root cause FTD Alzheimer’s $15BB-$25BB None LBD Peak sales potential..* Parkinson’s $4BB-$6BB CTE Peak sales potential..* ALS “Marginal” Effective Symptomatic Disease Modifying No Therapy Symptomatic Therapy Therapy Thera
Slide 5: Alzheimer's, Parkinson's and ALS are protein mis-folding diseases
Alzheimer’s, Parkinson’s and ALS are protein mis-folding diseases, where the toxic mis-folded proteins propagate in a prion-like manner Huntington’s disease Alzheimer’s disease Schizophrenia (huntingtin) (amyloid-beta and tau) (DISC1) Senile amyloidosis Type 2 diabetes (transthyretin) (amylin) Prion
Slide 6: ProMIS selective antibodies suited for gene therapy vectorization
ProMIS selective antibodies are uniquely well suited for gene therapy vectorization in mis-folded protein, neurodegenerative diseases ...But vectorization of antibodies Numerous benefits to vectorization in against mis-folded protein targets a gene therapy construct requires selectivity for the toxi
Slide 7: ProMIS unique capabilities create opportunity for near-term value creation
ProMIS unique capabilities, combined with technical advances in the field, create the opportunity for significant near-term value creation ProMIS unique capabilities to Advances in the field create highly selective Significant value creation antibodies Better Science… Highly selective ProMIS portfol
Slide 8: ProMIS: current portfolio of antibodies targeting toxic mis-folded proteins
ProMIS: current portfolio of antibodies selectively targeting toxic mis-folded proteins Predict Produce Prioritize Lead program early POC Scientific Literature: Mis-folded protein role Assess functional IND enabling Predict Immunize and screen benefit in vitro and in development in disease conformat
Slide 9: Anti-amyloid therapy in Alzheimer's disease
Anti-amyloid therapy in Alzheimer’s disease: targeting the toxic species of amyloid-beta 9
Slide 10: Updating the amyloid hypothesis: amyloid matters
Updating the amyloid hypothesis in light of aducanumab pivotal trial data: amyloid matters & ProMIS is on the right track targeting toxic AβOs • There is no question that amyloid plays a role in AD pathology • genetics, Icelandic/BACE population, unable to make amyloid never develop AD, while Down s
Slide 11: Aducanumab is approvable, PMN310 designed to be best in class
Updating the amyloid hypothesis in light of aducanumab pivotal trial data: aducanumab is approvable, PMN 310 designed to be “best in class” • Aducanumab differs from all failed programs - it does not bind the simplest form of amyloid - monomer. It only binds aggregated forms, oligomer and plaque (li
Slide 12: ProMIS history: evaluating positive aducanumab data to create PMN310
ProMIS history: evaluating positive aducanumab data to create best in class PMN310, selectively targeting toxic AβOs 2015/2016/2017 2018 2019 Biogen Phase Biogen 1b success pivotal trial (PRIME) positive data PMN310 ProMIS ProMIS Comparative portfolio started Data (Jan) expansion Evaluated positive
Slide 13: Despite positive aducanumab results, 2020 marks a new era
Despite positive aducanumab results, recent history fueled negative sentiments; however, 2020 marks a new era in AD therapeutic progress 2015/2016/2017 2018 2019 Biogen Phase Biogen EISAI BAN2401 Biogen stops Biogen 1b success accidentally Positive, then aducanumab corrected (PRIME) confusion over p
Slide 14: Aducanumab provides clinical benefit only at the highest dose
Aducanumab provides clinical benefit of 20% - 30% only at the highest dose, 10mg/kg - strong dose response curve PRIME Phase 1B -52 wks V4 pivotal high dose -72 wks EMERGE ENGAGE CDR -SB High dose (n=288) High dose (n=282) 10mg/kg 10mg/kg p<0.05 Difference v. placebo Difference v. placebo P<0.01 P<0
Slide 15: There are three forms of amyloid
There are three forms of amyloid, choosing the correct target is critical…. Toxic oligomers – Plaque – usually present, Monomer – Important thousands of scientific but no significant role in for brain health studies showing disease neurotoxicity Monomer plays a key Mis-folded, toxic oligomers Plaque
Slide 16: Targeting the wrong form(s) of amyloid is 0 for 37
Early amyloid targeted programs, typically designed 10-15 years ago, were targeted at amyloid monomer, or were non-selective..None has ever resulted in a positive phase 2 or phase 3 trial Toxic oligomers – Plaque – usually present, Monomer – Important thousands of scientific but no significant role
Slide 17: Aducanumab and BAN2401 first partially selective amyloid programs
Biogen’s aducanumab and EISAI’s BAN2401 are the first partially selective amyloid programs, targeted aggregated amyloid, both have had only successful trial results Toxic oligomers – Plaque – usually present, Monomer – Important thousands of scientific but no significant role in for brain health stu
Slide 18: Soluble toxic Aβ oligomers are the most neuropathogenic species
Alzheimer’s disease: soluble toxic Aβ oligomers – not plaque or monomers – are the most neuropathogenic Aβ species • Synapse abnormalities and memory impairment correlate poorly In vivo impairment of recognition memory with plaque burden in human and mouse AD1,2 by Ab oligomers, not monomers and not
Slide 19: Misfolded AβOs, not plaque, are the pathogenic species in AD
Misfolded amyloid beta oligomers – AβOs – and not amyloid plaque are the pathogenic species in AD “With about 2,000 AβO papers published since 2013…………The AβO hypothesis has all but supplanted the amyloid cascade. AβOs have not yet received the clinical attention given to amyloid plaques, which have
Slide 20: The logic supporting selective targeting of toxic AβOs
The logic supporting selective targeting of mis-folded, toxic AβOs Amyloid beta is a valid target for disease modifying therapy in AD - Results of aducanumab PRIME & V4 pivotal trials, and BAN 2401 phase 2 show efficacy on cognitive decline Toxic oligomers of amyloid beta are the correct target - Cl
Slide 21: ProMIS PMN310, best in class antibody for AD
ProMIS PMN310, best in class antibody for AD, selectively targeting toxic, mis-folded amyloid–beta oligomers 21
Slide 22: Binding the right form of amyloid beta is critical
Binding the right form of amyloid beta is critical: the toxic oligomer is the target Bapineuzumab Solanezumab Aducanumab PMN310 • Phase 2 failure • Phase 2 failure • Phase 2 & 3 success • Selective binding to • Phase 3 failure • Phase 3 failure • ARIA-E side effect oligomers • ARIA-E side effect ->
Slide 23: PMN310 lack of plaque binding suggests a safety advantage
ARIA-E associated with aducanumab, BAN2401 & bapineuzumab; PMN310 lack of binding to Aβ plaque strongly suggests a potential safety advantage Aducanumab PMN310 Plaque No binding to plaque binding or vascular deposits Vascular deposit binding PMN310 IgG4 isotype also correlated with lack of ARIA-E 23
Slide 24: Soluble low molecular weight toxic oligomers drive neurotoxicity
Not all oligomers are equivalent ..… soluble low molecular weight toxic oligomers drive neurotoxicity and disease progression • AD brain homogenates contain heterogeneous Size exclusion chromatography of AD brain extract Ab aggregates dominated by high molecular Dodecamer (12) weight species includi
Slide 25: huPMN310 shows superior binding to toxic oligomers from human AD brains
huPMN310 shows superior binding to toxic oligomers from human AD brains vs other antibodies directed against amyloid-beta 50 Binding Response (RU) 40 • Binding of antibodies to the toxic oligomer- enriched LMW fraction of soluble human AD 30 brain extract was evaluated by surface plasmon resonance (
Slide 26: Properties of PMN310 support better therapeutic potency
Properties of PMN310 support better Therapeutic Potency vs Biogen’s likely “first in class” aducanumab Therapeutic Potency Efficacy is dose-dependent - Maximize drug delivered to the toxic oligomers Avoid plaque Selectivity - (ARIA-E) Avoid target dose high distraction Bapineuzumab - - This profile
Slide 27: The largest products in industry history were best in class
The three largest products in industry history were not first in class, but “best in class” – the inventors identified improvements to existing drugs ProMIS following the “best in class” playbook: Peak • Took advantage of “proof of Sales biology” developed by earlier $BB’s products: the scientific $
Slide 28: Hypothetical Phase 1 biomarker readout
Hypothetical example – Phase 1 biomarker readout could show a disease modifying treatment effect in a dose dependent fashion at a cost of $5MM-$10MM Placebo/ Large Placebo dataset as an historical control natural history 100* dataset Potential biomarkers: 3 mg/kg NfL – Neuronal Loss Blood 10 mg/kg G
Slide 29: PMN310 development plan
PMN310 development plan – significant data readouts over coming 2-4 years Year 1 from adequate Year 2 Year 3 Year 4 capital Final IND enabling work Sporadic AD Phase 1: 3 month Pbo control, 9 month extension, MAD design AD in Down Syndrome - prevention, treatment, or both: Biomarker and clinical end
Slide 30: Anti-amyloid-β Program PMN310: potential best in class therapy
Anti-amyloid-β Program PMN310: potential best in class therapy for Alzheimer’s disease • Significant scientific and clinical data in the Alzheimer’s amyloid field, gathered over decades, provide clear support for the ProMIS strategy that led to PMN310 - Thousands of publications, over 30 clinical tr
Slide 31: Targeting the toxic species of alpha-synuclein for Parkinson's disease
Targeting the toxic species of alpha- synuclein for Parkinson’s disease and related syndromes 31
Slide 32: Alpha-synuclein is the major driver of Parkinson's disease and MSA
Alpha-synuclein is the major driver of Parkinson’s disease, Multiple System Atrophy (MSA) and other synucleinopathies • Synucleinopathies: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons located in the midbrain and the presence of in
Slide 33: Selectively target only the toxic alpha-synuclein aggregates
Therapeutic imperative: selectively target only the toxic a-synuclein aggregates • Alpha-synuclein exists in different forms including normal, physiologically important conformations and toxic forms: • Monomers play an important role in the regulation of synaptic Optimum vesicle trafficking and rele
Slide 34: ProMIS antibodies achieve the targeted binding profile
ALPHA-SYNUCLEIN ProMIS’ unique technology platform has created antibodies that achieve the targeted binding profile….better than other a-synuclein-directed antibodies Target Properties PMN Prothena/ BioArctic/ Neurimmune/ Antibodies Roche ABBVIE Biogen No binding to monomers ✔ X +/- X No binding to
Slide 35: ProMIS antibodies protect dopaminergic neurons against toxicity in vitro
ProMIS antibodies protect dopaminergic neurons against a-synuclein oligomer toxicity in vitro CONTROL Normal neurons in bright red Survival (dopaminergic neuron % of ocntrol) 120 ** ** ** ** ** 100 * * 80 a-SYN OLIGOMERS 60 Neurons killed by 40 toxic oligomers ol o 2) 2) ) ) 2) ) F PMN antibodies :2
Slide 36: ProMIS antibodies inhibit alpha-synuclein propagation
ProMIS antibodies inhibit a-synuclein propagation: decreased recruitment of endogenous rat a-syn into pathogenic phosphorylated aggregates Human PFF +/- PMN antibody Staining for rat phosphorylated a-syn aggregates 14 days Rat neurons Rat neurons ProMIS antibodies significantly decrease recruitment
Slide 37: MSA as a disease indication for therapeutic antibodies
Multiple system atrophy (MSA) as a disease indication for therapeutic antibodies targeting toxic species of a-synuclein • MSA is a rare neurodegenerative disease with an estimated prevalence of 3.4-4.9 a-syn glial cytoplasmic inclusions (GCI)2 cases per 100,000 population1 • MSA is characterized by
Slide 38: Potential development plan for alpha-synuclein program
Potential development plan for alpha-synuclein program: early proof of concept with an antibody; rapid route to approval with a gene therapy in MSA Antibody Final IND enabling work MSA patient Phase 1: multiple ascending dose - Alpha synuclein antibody Gene (MAD) design - IgG1 Therapy Vectorize lead
Slide 39: ProMIS alpha-synuclein program: Summary
ProMIS alpha-synuclein program: Summary • Scientific literature suggests a complex binding profile for an optimum antibody • Bind toxic oligomers and small soluble fibrils involved in propagation • Avoid physiologic monomer and tetramer, reduce adverse event odds, enable vectorization • Minimize bin
Slide 40: Targeting toxic species of TDP43 for ALS
Targeting toxic species of TDP43 for ALS 40
Slide 41: Prion-like propagation of mis-folded TDP43 drives ALS and FTLD
Prion-like propagation of mis-folded TDP43 is a driver of pathogenesis in ALS and frontotemporal lobar degeneration (FTLD) • Mis-folded protein aggregates of TDP43 are a pathological hallmark of ALS and FTLD1 • The stereotypical distribution of TDP43 pathology in ALS and FTD shows a spreading patter
Slide 42: ProMIS antibody against TDP43 is selective for mis-folded TDP43
ProMIS antibody against TDP43 is selective for mis-folded TDP43 Cytoplasmic mis-folded PMN antibody: No staining of WT nuclear TDP43, staining of mis- TDP43 (stained for HA tag) folded cytoplasmic TDP43 (co-localization in merged images) Confocal microscopy of HEK293 cells transduced with misfolding
Slide 43: Potential development plan for TDP43 program
Potential development plan for TDP43 program: early proof of concept with an antibody; rapid route to approval with a gene therapy in ALS Antibody Final IND enabling work ALS patient Phase 1: multiple ascending dose - TDP43 antibody Gene (MAD) design; - IgG1 Therapy Vectorize lead antibody IND enabl
Slide 44: Summary of mis-folded TDP43 antibody findings
Summary of mis-folded TDP43 antibody findings • Multiple antibodies generated with epitope binding affinity in the sub-nanomolar (mouse monoclonals) to sub-nanomolar (rabbit monoclonals) range • Antibodies identified with reactivity and specificity for aberrant cytoplasmic TDP43 aggregates in cell m
Slide 45: Outlook & Summary
ProMIS™ Neurosciences Outlook & Summary 45
Slide 46: Portfolio of antibodies creates numerous potential near term catalysts
ProMIS: current portfolio of antibodies selectively targeting toxic mis-folded proteins creates numerous potential near term catalysts Predict Produce Prioritize Lead program early POC Scientific Literature: Mis-folded protein role Assess functional IND enabling Predict Immunize and screen benefit i
Slide 47: ProMIS going forward: potential for numerous catalysts and value creation
ProMIS going forward : potential for numerous catalysts and value creation 2020 2021, 2022 Biogen Biogen Aducanumab BAN2401 Ph External Events BLA FDA Adv approval 3 data Filing Comm Clinical data in AD and Down PMN310 Syndrome AD – biomarkers, comparative Other ProMIS Potential partnering deals Con
Slide 48: ProMIS Neurosciences: Summary
ProMIS Neurosciences: Summary • ProMIS discovery platform provides a unique competitive advantage, with an unparalleled track record of creating antibodies highly selective for the toxic molecular species • ProMIS lead program PMN310 scientifically differentiated from Biogen’s aducanumab. - Aducanum
Slide 49: Thank You
Thank You Please feel free to contact us with any additional questions. Eugene Williams, Executive Chairman Elliot Goldstein, MD, CEO eugene.williams@promisneurosciences.com elliot.goldstein@promisneurosciences.com +1 (617) 460-0978 +1 (415) 341-5783 Website: www.promisneurosciences.com Twitter: htt
Slide 50: Experienced leadership team
Experienced leadership team Name Title Years of Experience Prior Experience § Former SVP at Genzyme, with senior roles integrating commercialization, drug development, and deal making Gene Williams Executive Chairman 25+ § Recently the CEO of Dart Therapeutics, an Orphan Disease drug development com
Slide 51: Independent board of directors
Independent board of directors Name Years of Experience Prior Experience § President and CEO of Sunovion CNS Development 25+ Canada ULC Anthony Giovinazzo § President, CEO and a Director of Cynapsus Therapeutics from 2009 to 2016 and one of the three original inventors and patent holders of the comp
Slide 52: Scientific Advisory Board
Scientific Advisory Board Name Years of Experience Prior Experience Affiliations § Medical Director & Principal Investigator of Toronto Memory Program Sharon Cohen, MD 20+ § FRCPC in neurology from Royal College of Physicians of Canada and a fellowship in Behavioural Neurology from the University of
Slide 53: Business Advisory Board
Business Advisory Board Name Years of Experience Prior Experience Affiliations § CEO and Founder of SweetSpot Therapeutics Ltd Nigel Burns, PhD 25+ § Served as Senior Vice President of Cambridge Antibody Technology § Entrepreneur-in-residence at Polaris Partners Michael Higgins, MBA 25+ § Previously
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