Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Technical Presentation (December 2019)
19 slides from Wave Life Sciences's technical presentation, Dec 30, 2019
Slide 1: PRECISION-HD2 Topline Results
PRECISION-HD2 Topline Results December 30, 2019 Exhibit 99.2
Slide 2: Forward-looking statements
Forward-looking statements This document contains forward-looking statements. All statements other than statements of historical facts contained in this document, including statements regarding possible or assumed future results of operations, preclinical and clinical studies, business strategies, r
Slide 3: Agenda
Agenda Paul Bolno, MD, MBA President & CEO | Wave Life Sciences Opening Remarks Michael Panzara, MD, MPH Chief Medical Officer| Wave Life Sciences PRECISION-HD2 topline results and clinical trial expansion Q&A Paul Bolno, MD, MBA President & CEO | Wave Life Sciences SNP3 and closing remarks
Slide 4: Huntington's disease: a hereditary, fatal disorder
Huntington’s disease: a hereditary, fatal disorder Sources: Auerbach W, et al. Hum Mol Genet. 2001;10:2515-2523. Dragatsis I, et al. Nat Genet. 2000;26:300-306. Leavitt BR, et al. J Neurochem. 2006;96:1121-1129. Nasir J, et al. Cell. 1995;81:811-823. Reiner A, et al. J Neurosci. 2001;21:7608-7619. W
Slide 5: Wave approach: novel, allele-selective silencing
Utilize association between single nucleotide polymorphisms (SNPs) and genetic mutations to specifically target errors in genetic disorders, including Huntington’s disease (HD) Potential to provide treatment for up to 80% of HD population Wave approach: novel, allele-selective silencing Source: Kay,
Slide 6: Michael Panzara, MD, MPH, Chief Medical Officer
Michael Panzara, MD, MPH Chief Medical Officer
Slide 7: PRECISION-HD2 clinical trial design
PRECISION-HD2 clinical trial design Phase 1b/2a trial Single Dose (3:1) Multidose Randomization 3:1 196 1 At least 8 week washout CSF sample Dose 28 56 84 112 Study Day* 140 OLE Initiated October 2019 2 mg 4 mg 8 mg 16 mg 32 mg Multidose Cohorts Expected to initiate in January 2020 N = 12 per cohort
Slide 8: WVE-120102 generally safe and well tolerated
WVE-120102 generally safe and well tolerated A total of 72% of those who received WVE-120102 experienced an adverse event (AE) as compared with 83% on placebo, mostly mild to moderate in intensity Most common AEs (those occurring in at least 10% of patients on WVE-120102) were headache, procedural p
Slide 9: Significant reduction in CSF mHTT WVE-120102 compared to placebo
Significant reduction in CSF mHTT WVE-120102 compared to placebo Pooled Placebo (N=12) Pooled WVE-120102 (N=27) Median (% Change from Baseline) 9.5 -6.0 95% CI (%) 1.77, 20.38 -9.57, 4.85 Difference (%)* -12.4 95% CI (%) -24.58, -0.40 p-value† <0.05 *Hodges-Lehmann non-parametric shift estimates of
Slide 10: Total HTT and wild-type HTT assessment
Healthy or wild-type HTT transcript is required to produce healthy HTT protein which is important for neuronal function There is currently no assay available to directly measure wtHTT in the CSF Total HTT assay, developed by CHDI Foundation, measures total HTT protein to indirectly assess effects on
Slide 11: Neurofilament light chain
Neurofilament light chain Neurofilament light chain (NfL) is an indicator of axonal damage and is elevated in many neurological disorders, including Huntington’s disease No change in CSF neurofilament light chain (NfL) between WVE-120102 and placebo-treated groups Byrne LM, Rodrigues FB, Johnson EB,
Slide 12: Advancing PRECISION-HD programs
Advancing PRECISION-HD programs PRECISION-HD2 (WVE-120102) WVE-120102 demonstrated statistically significant reduction in mutant HTT compared to placebo Topline data support advancing to higher doses No difference in total HTT or neurofilament light chain in treated patients compared to placebo Data
Slide 13: Paul Bolno, President and CEO
Paul Bolno President and CEO
Slide 14: SNP3: Broadening reach in Huntington's disease
SNP3: Broadening reach in Huntington’s disease Due to overlap, ~80% of the total HD patient population carry SNP1 and/or SNP2 and/or SNP3 In vivo models for SNP3 available for preclinical development SNP3 % Huntington’s Disease Patient Population with SNP SNP1 SNP2 SNP3 SNP1 SNP2 SNP1 SNP2 SNP3 ~50%
Slide 15: SNP3: Potent mutant HTT knockdown and allele-selective silencing
SNP3: Potent mutant HTT knockdown activity and demonstration of allele-selective silencing Stereopure compounds selectively deplete mutant HTT mRNA in preclinical study involving heterozygous patient-derived neurons [Left] HTT mRNA remaining in iCell neurons (homozygous for SNP) incubated with the i
Slide 16: SNP3: Durable in vivo mutant HTT knockdown with stereopure compounds
SNP3: Durable in vivo mutant HTT knockdown with stereopure compounds Knockdown persists for 12 weeks Oligonucleotide or PBS (3 x 100 mg ICV) was delivered to BACHD mice. Relative percentage of HTT/TUBB3 mRNA in cortex with respect to levels in PBS-treated mice is shown at 2-12 weeks post-injection.
Slide 17: Anticipated upcoming Wave milestones
Anticipated upcoming Wave milestones CNS 2H 2020: PRECISION-HD2 data from 32 mg cohort in Huntington’s disease 2H 2020: PRECISION-HD1 topline data, including 32 mg cohort, in Huntington’s disease 2H 2020: Initiate clinical development of SNP3 program in Huntington’s disease 2H 2020: Initiate clinica
Slide 18: Q&A
Q&A
Slide 19: PRECISION-HD2 Topline Results
PRECISION-HD2 Topline Results December 30, 2019
Wave Life Sciences — Technical Presentation (December 2019) on 6ix