Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Technical Presentation (October 2026)
17 slides from Alnylam Pharmaceuticals's technical presentation, October 2026
Slide 1: Interim Data From a Phase 1b Study of ALN-HTT02 in Huntington's Disease
Interim Data From a Phase 1b Study of ALN-HTT02, an Investigational RNA Interference Therapeutic Targeting Exon 1 of Huntingtin for HTT-lowering in People with Huntington’s Disease Sarah Tabrizi1, Edward J Wild1, Blair Leavitt2, Carsten Saft3, Mark Guttman4, Alexandre Sostelly5, Ryan Gryder5, Sean R
Slide 2: Disclosure for Sarah Tabrizi, MD, PhD
Disclosure for Sarah Tabrizi, MD, PhD Conflict Disclosure Consultant 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 and efficacy of ALN-HTT02 have not be
Slide 3: RNA Interference in the CNS
RNA Interference in the CNS C16 Delivery Platform Enables RNAi Therapeutics to Reduce Production of Disease-Associated Proteins in the CNS1 Synthetic double-stranded small interfering RNA (siRNA) designed Long-lasting protein to target specific mRNA2–4 reduction without 2. siRNA engages RISC, perman
Slide 4: RNAi is Distinct from ASOs
RNAi is Distinct from ASOs RNAi1–3 ASO ASO1-3,8,10 1–3 • RNAi has distinct chemistry and mechanism to the ASO class • Catalytic mechanism provides potential for high potency and long duration of action, supporting infrequent administration • Six approved products across rare and prevalent diseases •
Slide 5: ALN-HTT02 Targets Exon 1 of HTT
ALN-HTT02 Targets Exon 1 of HTT Leveraging C16-siRNA Platform for CNS Delivery HTT Alleles in HD • ALN-HTT02 is an intrathecally administered investigational FL Wild-type FL Mutant HTT1a RNAi therapeutic for Huntington’s disease (HD) – ALN-HTT02 targets a conserved mRNA sequence within HTT exon 1 Ex
Slide 6: ALN-HTT02 Durably Lowered HTT Throughout the Brain in Non-Human Primates
ALN-HTT02 Durably Lowered HTT Throughout the Brain with an Encouraging Safety Profile in Non-Human Primates • Across multiple NHP studies up to 12 months in duration:1,2 – No neurological abnormalities – No changes in CSF inflammatory markers or neurofilament light chain (NfL) – No histological chan
Slide 7: Phase 1b Study of ALN-HTT02 Ongoing in Adults with HD
Phase 1b Study of ALN-HTT02 Ongoing in Adults with HD Study Designed in Partnership with the HD Community Phase 1b, Randomized, Double-Blind, Placebo-Controlled Trial Study objective • Evaluate the safety, tolerability, and PK/PD effects of single IT doses of ALN-HTT02 Key inclusion criteria • Aged
Slide 8: Phase 1b Study Design and Randomization
Phase 1b Study of ALN-HTT02 Ongoing in Adults with HD Study Designed in Partnership with the HD Community Dose 1 or placebo (2:1) N=6 Endpoints OLE • Primary endpoint Dose 2 or placebo (2:1) N=6 (ALN-HTT02 or placebo) – Safety and tolerability Unblinding at Month 6a All participants can • Secondary/
Slide 9: Baseline Patient Characteristics were Similar Across Cohorts
Baseline Patient Characteristics were Similar Across Cohorts ALN-HTT02 ALN-HTT02 ALN-HTT02 ALN-HTT02 ALN-HTT02 Demographic/Characteristic dose 1 or placebo dose 2 or placebo dose 3 or placebo dose 4 or placebo dose 5 or placebo (N=6) (N=6) (N=12) (N=12) (N=12) Age, years, mean (SD) 52.2 (8.8) 54.7 (
Slide 10: Dose-Dependent CSF mHTT Reduction Demonstrated with SMCxPRO Assay
Dose-Dependent CSF mHTT Reduction Demonstrated with SMCxPRO Assay Up to 64% Mean Reduction at Month 3 and up to 80% Individual Reduction in CSF mHTT After a Single IT Dose of ALN-HTT02 Placebo ALN-HTT02 mHTT reduction (N=12) Dose 1 (N=5) Dose 2 (N=4) Dose 3 (N=9) Dose 4 (N=9) Dose 5 (N=9) Mean maxim
Slide 11: Dose-Dependent CSF mHTT Reduction Confirmed with Independent NULISA Assay
Dose-Dependent CSF mHTT Reduction Confirmed with Independent NULISA Assay Up to 60% Mean Reduction at Month 3 and up to 83% Individual Reduction in CSF mHTT After a Single IT Dose of ALN-HTT02 Assay SMCxPRO NULISA Participants with post- baseline measurement 16 (33.3) 0 (0) below LLoQ, n (%) Placebo
Slide 12: Blinded Safety Summary
Blinded Safety Summary Active and Placebo Participants Pooled Within Cohort Owing to Ongoing Blinded Study ALN-HTT02 ALN-HTT02 ALN-HTT02 ALN-HTT02 ALN-HTT02 Category dose 1 or placebo dose 2 or placebo dose 3 or placebo dose 4 or placebo dose 5 or placebo (N=6) (N=6) (N=12) (N=12) (N=12) Duration of
Slide 13: No Dose-Dependent Increases in CSF Inflammatory Markers
No Dose-Dependent Increases in CSF Inflammatory Markers CSF Total Protein CSF WBC CSF total protein data from one participant in each of the dose 3 and dose 4 groups, and the 12-month data point from one participant in the dose 1 group, were excluded owing to suspected site input error. Dashed lines
Slide 14: No Dose-Dependent Increases in CSF NfL
No Dose-Dependent Increases in CSF NfL NfL is a Biomarker of Neuroaxonal Injury CSF NfL – Absolute CSF NfL – Fold Change Placebo range Placebo range Shaded placebo range indicates maximum and minimum observed individual placebo values. BL, baseline; CSF, cerebrospinal fluid; NfL, neurofilament light
Slide 15: No Dose-Dependent Increases in Ventricle Size
No Dose-Dependent Increases in Ventricle Size No Increases Beyond Placebo Range Despite Robust mHTT-Lowering Placebo range Placebo ALN-HTT02 ALN-HTT02 ALN-HTT02 ALN-HTT02 ALN-HTT02 NULISA assay (N=12) dose1 (N=5) dose 2 (N=4) dose 3 (N=9) dose 4 (N=9) dose 5 (N=9) Mean maximum observed 4.9 (13.2) 28
Slide 16: ALN-HTT02-001 Phase 1b Interim Results Summary
Scan to view presentation Country restrictions apply ALN-HTT02-001 Phase 1b Interim Results Summary QR code • ALN-HTT02 is an investigational RNAi therapeutic utilizing the C16-siRNA platform, in development for treatment of HD – ALN-HTT02 is designed to lower all forms of HTT protein in the CNS, in
Slide 17: Thank you to the participants, families, investigators, and study staff
Thank you to the participants, their families, investigators, and study staff for supporting the ALN-HTT02-001 study Thank you to our collaborators and HD advocacy groups for ongoing advice and support of the program Thank you for the opportunity to share our work today Scan to view presentation Cou
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