Clene (CLNN) 37th Annual ROTH Conference summary

Regulatory and clinical development updates

• Two key FDA meetings in 2023 led to a shift in regulatory flexibility, with the agency recommending leveraging real-world data from the NIH-sponsored Expanded Access Protocol for ALS.

• The NIH grant enabled enrollment of up to 180 ALS patients, with comprehensive neurofilament biomarker collection via home-based phlebotomy, aiming for robust six- and nine-month data by summer.

• The agency requested a pre-specified statistical analysis plan (SAP) for neurofilament data, with a meeting expected in 30–60 days to align on methodology before data analysis.

• If neurofilament data from the expanded cohort is concordant with prior HEALEY results, it could support an NDA for accelerated approval, with a potential advisory committee review next year.

• Phase 3 RESTORE study will be underway by summer, with patients randomized and dosed prior to NDA submission, focusing on time-to-event endpoints (survival and need for permanent assisted ventilation).

Clinical data highlights and survival analysis

• CNM-Au8 remains the only asset among eight HEALEY regimens to show a survival benefit, with significant results at six months and ongoing open-label extension data.

• Survival data from the expanded access and open-label cohorts show some patients on therapy for over five years, exceeding typical ALS survival expectations.

• The agency is now more focused on neurofilament and survival endpoints rather than ALS-FRS functional scales.

• Statistical significance in survival and neurofilament endpoints is being used to inform phase 3 design and regulatory discussions.

• Natural history controls and post-hoc analyses are being used to contextualize survival outcomes, though the agency prefers prospective biomarker-driven evidence.

Multiple sclerosis (MS) program progress

• Three-year follow-up data in MS showed improved cognition and remyelination, measured by visual evoked potential and MRI, in patients on full DMT but with residual deficits.

• Additional MS data will be presented at the upcoming American Academy of Neurology meeting, including two years of follow-up from the VISIONARY program.

• An end-of-phase 2 meeting with the agency is planned for late 2024, with a phase 3 trial in fully controlled MS patients targeted for next year.

• The REPAIR-MS program is ongoing, assessing CNM-Au8 in progressive MS patients, with data expected later this year.