NeuroSense Therapeutics Ltd. announced additional positive results from its 12-month PARADIGM Phase 2b study of PrimeC in ALS patients. In the study, complication-free survival revealed a 57% difference in favor of PrimeC over placebo after 12 months of treatment in the Intent to Treat (ITT) population and demonstrated an outcome of 73% (p=0.02) difference in favor of PrimeC across placebo after 12 months of treatment In the pre-defined Per Protocol Population (PP). NeuroSense intends to submit these 12-month results to regulatory agencies, including the FDA, to discuss PrimeC's path forward in the short term.

Previously, NeuroSense reported that PrimeC significantly slowed disease progression by 36% (p=0.009) and improved survival rates by 43% compared to placebo. This outcome underscores the importance of early treatment and the potential of PrimeC as a disease-modifying drug. The latest results from the PARADIGM study are incredibly encouraging and provide compelling evidence of PrimeC's potential to significantly benefit people living with ALS.

The substantial improvement in complication-free survival and the consistent slowing of disease progression highlight PrimeC's promise as an effective treatment. Given that, for many clinicians and people with ALS, therapeutic options have recently been significantly limited; the urgency for effective new therapies is greater than ever. This development brings renewed hope to patients, and I am eagerly looking forward to seeing the program enter Phase 3 to advance the clinical development of this product," said Jeremy M. Shefner, M.D., Ph.D., Professor of Neurology at the Barrow Neurological Institute, Phoenix, Ariz., and a NeuroSense advisor.

The number of people living with ALS is expected to grow by 24% by 2040 in the U.S. and EU. Disease progression is measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), which is the most widely used ALS tracking tool accepted by the FDA, utilized by neurologists treating ALS patients, in clinical trials, and by other regulators to determine disease progression. It tracks 12 changes in a person's physical abilities over time including functions such as: speech, walking, climbing stairs, dressing/hygiene, handwriting, turning in bed, cutting food, salivation, swallowing, and breathing.

PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b (NCT05357950) clinical trial of PrimeC in ALS. Most patients enrolled in both the active and placebo arms of the trial were concurrently treated with Riluzole, the ALS standard of care medication, indicating PrimeC slowed disease progression well beyond the level afforded by the FDA-approved ALS drug. PrimeC, NeuroSense's lead drug candidate, is a novel extended-release oral formulation composed of a unique fixed-dose combination of two FDA-approved drugs: ciprofloxacin and celecoxib.

NeuroSense completed a Phase 2a clinical trial, which met its safety and efficacy endpoints, including reducing functional and respiratory deterioration and statistically significant changes in ALS-related biological markers, indicating PrimeC's biological activity. PrimeC was granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medicines Agency. These risks include unexpected R&D costs or operating expenses, a delay in the reporting of additional results from PARADIGM clinical trial, the timing of expected regulatory and business milestones, risks associated with meeting with the FDA to determine the best treatment.