Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — EHDN & Enroll-HD Congress 2024
12 slides from Alnylam Pharmaceuticals's conference presentation, Sep 12, 2024
Slide 1: ALN-HTT02, a Novel C16-siRNA Conjugate for HTT-lowering in the CNS
ALN-HTT02, a Novel C16-siRNA Conjugate for HTT-lowering in the CNS Kevin Sloan1, on behalf of the ALN-HTT02 program team 1Alnylam Pharmaceuticals Inc, Cambridge, MA, USA Presented at the EHDN & Enroll-HD Congress in Strasbourg, France September 12-14, 2024
Slide 2: Relevant Disclosures for Kevin Sloan, PhD
Relevant Disclosures for Kevin Sloan, PhD Conflict Disclosure Employee Alnylam Pharmaceuticals Shareholder Alnylam Pharmaceuticals ALN-HTT02 ALN-HTT02 is an investigational drug being studied for the treatment of Huntington’s disease. ALN-HTT02 is not approved by any health authority, and the safety
Slide 3: HTT is a Genetically Validated Target for Huntington's Disease
HTT is a Genetically Validated Target for Huntington’s Disease1 No approved disease-modifying treatments exist, reflecting a critical unmet need2 • Huntington's disease (HD) is progressive and fatal, driven by mutant huntingtin (HTT)1,3 – Toxic, broadly disruptive gain of function – CAG repeat expan
Slide 4: Alnylam has Pioneered Development of RNAi Therapeutics
Alnylam has Pioneered Development of RNAi Therapeutics Over 20 years of platform learning & optimization petunias 2013 2022 2006 Napoli and Jorgensen report First silencing of a liver C16 conjugation enables Fire and Mello that violet petunias turned Alnylam founded gene using GalNAc siRNA delivery
Slide 5: RNA Interference Mechanism of Action
RNA Interference Mechanism of Action Harnesses an endogenous process to lower expression of disease-associated target proteins • RNAi is a natural biological process to regulate gene expression1 • Synthetic small interfering RNAs (siRNAs) designed to specifically degrade mRNA encoding a disease- ass
Slide 6: First Translation of RNAi in the CNS
First Translation of RNAi in the CNS Preclinical and Phase 1 data of C16-siRNA demonstrate robust lowering of target protein expression with encouraging safety in Alzheimer's disease Preclinical Results with APP-lowering siRNA1,2 Interim Phase 1 SAD Results of Mivelsiran in Early-Onset AD3 • IT dosi
Slide 7: ALN-HTT02 is an Investigational RNAi Therapeutic Designed to Reduce HTT Protein Expression
ALN-HTT02 is an Investigational RNAi Therapeutic Designed to Reduce HTT Protein Expression in the CNS Leveraging a Clinically-Validated C16-siRNA Delivery Platform Therapeutic hypothesis • ALN-HTT02 targets a conserved mRNA sequence within exon 1 • Designed to reduce expression of all HTT protein sp
Slide 8: Single Dose of ALN-HTT02 Demonstrates Broad CNS Distribution and Durable HTT-Lowering in NHP
Single Dose of ALN-HTT02 Demonstrates Broad CNS Distribution and Durable HTT-Lowering in NHP1 PK/PD Profile Consistent with Prior RNAi Experience in the CNS • Observations following a single dose of ALN-HTT02: Single IT Dose of ALN-HTT02 – Widespread distribution across CNS regions – Durable HTT-low
Slide 9: HTT-Lowering via Multiple Doses of ALN-HTT02 is Well Tolerated in NHP
HTT-Lowering via Multiple Doses of ALN-HTT02 is Well Tolerated in NHP1 Safety Profile Supports Continued Development • Observations following multiple doses of ALN-HTT02 MultipleITITDoses Multiple Dosesof ofALN-HTT02 ALN-HTT02 (Q3M (Q3Mfor for66Months) Months) at 3 dose levels: 120 % HTT Protein Rem
Slide 10: A Phase 1b Study of ALN-HTT02 in Adult Patients with HD
A Phase 1b Study of ALN-HTT02 in Adult Patients with HD Placebo-controlled single ascending dose study evaluating safety, tolerability, and PK/PD1 Study population • Age 25 to 70 years with >39 CAG repeats • HD-ISS Stage 2 or early Stage 3 Single Open-label2 Dose (Placebo-treated only) Randomization
Slide 11: Summary
Summary • Alnylam’s clinically-validated siRNA platform may offer a new approach for HTT-lowering in the CNS – Encouraging profile in another CNS siRNA development program (mivelsiran, targeting APP) • ALN-HTT02 is an investigational RNAi therapeutic designed to durably lower all forms of mHTT, incl
Slide 12: Thank you to the patients, their families, investigators, and study staff
Thank you to the patients, their families, investigators, and study staff for participation in the ALN-HTT02-001 study Thank you to our collaborators and HD advocacy groups for ongoing advice and support of the program Thank you to the EHDN organizers for the opportunity to share our work
Alnylam Pharmaceuticals — EHDN & Enroll-HD Congress 2024 on 6ix