Wave Life Sciences (WVE) 12th Annual Cantor Fitzgerald Global Healthcare Conference summary

Advances in RNA editing and therapeutic innovation

• RNA editing has achieved high potency, specificity, and durability, with tight inter-patient variability and clear correction of disease-causing mutations, exemplified by progress in AATD and PNPLA3 programs.

• Chemistry enhancements and novel oligo designs have improved editing efficiency, enabling broader applications, including extrahepatic targets and new therapeutic areas.

• Bifunctional modalities and dual siRNAs are being developed to address complex diseases, with ongoing innovation expected to be highlighted at the upcoming R&D Day.

• Clinical data support the superiority of correction over enzyme silencing, with protein correction leading to improved disease outcomes and durability.

• Regulatory and commercial strategies are evolving, with endpoints like CT densitometry and holistic patient profiles guiding trial designs and payer engagement.

AATD and regulatory strategy

• FDA meeting scheduled for end of summer/fall, with updated guidance to follow written feedback; focus on efficient trial designs that may allow for full or accelerated approval.

• CT densitometry is being considered as a key endpoint, supported by ongoing validation and regulatory acceptance.

• Clinical trial designs aim to address both lung and liver manifestations, reflecting the continuum of disease in AATD patients.

• Durable editing and correction are observed, with dose selection for pivotal trials informed by multi-dose cohort data; monthly or less frequent dosing is anticipated.

• RNA editing is positioned as a transformative approach compared to protein replacement, offering sustained protection and functional correction.

Inhibin E program and obesity/cardiometabolic pipeline

• Phase II-A study in obesity is enrolling well, with data expected this year; study design enables assessment of both diabetics and non-diabetics, with endpoints including body composition, liver fat, and cardiometabolic markers.

• Inhibin E silencing shows potent reduction in visceral and subcutaneous fat, with meaningful reductions in waist circumference and potential for regulatory approval based on 5% weight loss threshold.

• Combination and maintenance studies with incretins are planned, aiming to address the full continuum of obesity care, including post-GLP-1 settings.

• Visceral fat reduction is recognized as clinically meaningful, with ongoing discussions with regulators and advocacy groups to establish it as a functional biomarker.

• The program is designed to unlock multiple cardiometabolic indications, leveraging genetic evidence and robust trial endpoints to maximize value and differentiation.