Amylyx Pharmaceuticals, Inc. · NASDAQ:AMLX
Amylyx Pharmaceuticals — Corporate Update (July 2023)
24 slides from Amylyx Pharmaceuticals's corporate update, Jul 26, 2023
Slide 1: Progressive Supranuclear Palsy (PSP) Investor and Analyst Conference Call
Exhibit 99.1 Progressive Supranuclear Palsy (PSP) Investor and Analyst Conference Call July 26, 2023
Slide 2: On Today's Call
On Today’s Call • Welcome Lindsey Allen, Head, Investor Relations and Communications, Amylyx • Opening Remarks Josh Cohen and Justin Klee, Co-CEOs, Amylyx • AMX0035 Scientific Rationale in PSP Dr. Jamie Timmons, Head, Global Medical Strategy and Communications, Amylyx • PSP Treatment Landscape Prof.
Slide 3: Disclaimer
Disclaimer Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results
Slide 4: AMX0035 Scientific Rationale in PSP
AMX0035 Scientific Rationale in PSP Dr. Jamie Timmons Head, Global Medical Strategy and Communications, Amylyx 4
Slide 5: Our mission is to one day end the suffering caused by neurodegenerative diseases
Our mission is to one day end the suffering caused by neurodegenerative diseases. 5
Slide 6: Neurodegenerative Diseases Share Interconnected, Hallmark Pathological Pathways
Neurodegenerative Diseases Share Interconnected, Hallmark Pathological Pathways Pathological Protein Aggregation Amyotrophic Lateral Sclerosis (ALS) • TDP43, tau, SOD1, FUS, DPRs Tauopathies; e.g., Progressive Supranuclear Palsy (PSP) • tau Alzheimer’s Disease • tau, Aβ The interconnectedness of the
Slide 7: AMX0035 Acts on Several Shared Hallmark Pathways to Reduce Neuronal Cell Death
AMX0035 (Sodium Phenylbutyrate and Taurursodiol) Acts on Several Shared 1-9 Hallmark Pathways to Reduce Neuronal Cell Death Pathological Neuronal Cell Death Protein Aggregation • In vitro evidence of protecting 2 • Reduces tau in neurons from death neurodegenerative • Affects key pathways leading di
Slide 8: PSP is a Rare, Progressive and Fatal Tauopathy
PSP is a Rare, Progressive and Fatal Tauopathy • Rare neurological disorder affecting ESTIMATED PREVALENCE: body movements, walking and 1,2 balance, and eye movement. 7 in 100,000 worldwide • Lack of disease modifying therapies ESTIMATED INCIDENCE: creates significant unmet need. 2 0.81 in 100,000 w
Slide 9: Pathophysiologic Changes Underlying PSP Provide Multiple Pathways to Target
Pathophysiologic Changes Underlying PSP Provide Multiple Pathways to Target M MO OB BP P,, S ST TX X6 6,, E EIIF F2 2A AK K3 3,, M MA AP PT T G Ge en ne e M Mu ut ta at tiio on ns s T Ta au u D Dy ys sf fu un nc ct tiio on n T TR RIIM M1 11 1 G Ge en ne e M Mu ut ta at tiio on ns s O Ox xiid da at t
Slide 10: AMX0035 May Influence PSP Tau Pathology through Multiple Mechanisms
1-9 AMX0035 May Influence PSP Tau Pathology through Multiple Mechanisms M MO OB BP P,, S ST TX X6 6,, E EIIF F2 2A AK K3 3,, M MA AP PT T G Ge en ne e M Mu ut ta at tiio on ns s T Ta au u D Dy ys sf fu un nc ct tiio on n T TR RIIM M1 11 1 G Ge en ne e M Mu ut ta at tiio on ns s O Ox xiid da at tiiv
Slide 11: Preclinical Data Support Sodium Phenylbutyrate (PB) for Potential Treatment of PSP
Preclinical Data Support Sodium Phenylbutyrate (PB) for Potential Treatment of PSP MOBP, STX6, EIF2AK3, MAPT Gene Mutations Tau Dysfunction PB is Effective in PSP Mouse Model, TRIM11 Gene Mutations Reduced Tau in AD Mouse Model O O Oxx xiiid d da a att tiiiv v ve e e IIIn n njjju u ur rry yy/ / / Ta
Slide 12: Preclinical Data Support Taurursodiol (TURSO) for Potential Treatment of PSP
Preclinical Data Support Taurursodiol (TURSO) for Potential Treatment of PSP MOBP, STX6, EIF2AK3, MAPT Gene Mutations Tau Dysfunction TURSO reduced p-tau in cellular model of TRIM11 Gene Mutations 3 metabolic stress Oxidative Injury/ Tau Clearance T Ta au u C Clle ea ar ra an nc ce e Decreased Energ
Slide 13: Numerous Preclinical Studies Show AMX0035 Combination Targets Multiple Pathways
Numerous Preclinical Studies Show that AMX0035 Combination Targets Multiple Pathways Simultaneously to Prevent or Slow Cell Death 2 Dose-Matrix Study: Profilin Mouse Model of ALS 1 Primary Cortical Neuron Damage Model I In n v viit tr ro o,, A AM MX X0 00 03 35 5 c co om mb biin na at tiio on n d de
Slide 14: Numerous Preclinical Studies Show AMX0035 Combination Targets Multiple Pathways
Numerous Preclinical Studies Show that AMX0035 Combination Targets Multiple Pathways Simultaneously to Prevent or Slow Cell Death 2 Dose-Matrix Study: Profilin Mouse Model of ALS 1 Primary Cortical Neuron Damage Model 2 26 6 p pr riim ma ar ry y p ph ha ar rm ma ac co od dy yn na am miic c s st tu u
Slide 15: AMX0035 Significantly Lowered CSF Tau and p-Tau in Alzheimer's Trial
AMX0035 Significantly Lowered CSF Tau and p-Tau in Randomized Placebo Controlled Trial in People with Alzheimer's Disease Week 24 Mean (SE) CSF t-tau Week 24 Mean (SE) CSF p-tau181 Change From Baseline Change From Baseline 40 Placebo AMX0035 Placebo AMX0035 20 0 0 8.8 -20 –0.27 (15.2) -10 (2.9) -40
Slide 16: AMX0035 Shown to Reduce Tau Protein in Proteomic Analysis
AMX0035 Shown to Reduce Tau Protein in Proteomic Analysis Tau Protein 288 Of 288 proteins measured in CSF and plasma, Tau protein was the most significantly changed protein 1 by AMX0035 1. Data on File 16 The Proteomic analysis was a pre-specified, exploratory analysis in the PEGASUS trial of AMX003
Slide 17: AMX0035 Slowed Disease Progression and Prolonged Survival in ALS
1,2 AMX0035 Slowed Disease Progression and Prolonged Survival in ALS 3-5 ALS and PSP Share Several Phenotypic Features and Shared Disease Mechanisms 3 Suggests that a Drug Effective for ALS May be Effective for PSP 3 4,5 Shared Disease Mechanisms Shared Phenotypic Features Unfolded protein response
Slide 18: Key Takeaways
Key Takeaways • PSP is a tauopathy associated with tau dysfunction, tau aggregation and widespread neurodegeneration. • Multiple pathways, are implicated in tau pathology in PSP. • AMX0035 is proposed to mitigate tau pathology in PSP through multiple pathways. • Pre-clinical and clinical evidence su
Slide 19: ORION Phase 3 PSP Trial Design
ORION Phase 3 PSP Trial Design Dr. Lahar Mehta Head, Global Clinical Development, Amylyx 19
Slide 20: Completed PSP Clinical Studies Exhibit Consistent and Measurable Progression
Worsening disability Completed PSP Clinical Studies Exhibit Consistent and Measurable Progression on Validated Endpoint Dam et al 2021. Höglinger et al 2021. Boxer et al 2014. Three large, global clinical trials conducted to date show consistent progression of ~10 points/year on Progressive Supranuc
Slide 21: ORION: Phase 3 Clinical Trial of AMX0035 in PSP
ORION: Phase 3 Clinical Trial of AMX0035 in PSP Primary Objective: To assess the impact of AMX0035 compared Key Eligibility Criteria to placebo on disease progression rate as measured by PSPRS • Adults 40-80 years old • Possible or Probable PSP (Steele- Richardson-Olszewski Syndrome) 1,2 AMX0035 acc
Slide 22: ORION Clinical Trial Endpoints
ORION Clinical Trial Endpoints Disease Progression Primary 1 • Total PSPRS score (28-item) Endpoint Disease Progression Motor Aspects of Activities of Secondary Plan to initiate trial by 1 • Modified 10-item PSPRS Daily Living Endpoints year-end 2023 2 score• MDS-UPDRS Part II score Brain Atrophy Bi
Slide 23: PSP Meets Rigorous Criteria for Our Next Potential Indication for AMX0035
PSP Meets Rigorous Criteria for Our Next Potential Indication for AMX0035 Clear unmet need Strong scientific rationale Biomarker evidence Adjacencies and synergies with ALS Existing and robust understanding of the natural history of the disease Interest and support from KOLs and advocacy groups 23
Slide 24: Q&A Session
Q&A Session 24
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