Brainstorm Cell Therapeutics (BCLI) Status Update summary

ALS disease landscape and treatment challenges

• ALS is a heterogeneous, progressive neurodegenerative disease with significant variability in onset, progression, and survival, complicating clinical trial design and treatment development.

• Only a few approved therapies exist, each with modest efficacy, highlighting a large unmet need for effective disease-modifying treatments.

• Genetic and phenotypic diversity, delayed diagnosis, and variable progression rates are major obstacles in both research and clinical care.

• Biomarkers are increasingly important for stratifying patients, monitoring disease, and guiding targeted therapies.

Clinical trial design and regulatory alignment

• The new phase III-B trial for NurOwn is designed to enroll early-stage ALS patients, with less than two years from symptom onset and specific functional criteria.

• The primary endpoint is change from baseline in ALSFRS-R at 24 weeks, with secondary endpoints including survival, muscle strength, and biomarker changes.

• The trial features a double-blind period followed by an open-label extension, allowing all participants eventual access to NurOwn.

• The protocol was developed under a Special Protocol Assessment (SPA) agreement with the FDA, a first in ALS, ensuring regulatory alignment for potential approval.

Efficacy signals and biomarker findings

• Prior phase III data showed a statistically significant benefit for NurOwn in early-stage patients, with a two-point or greater improvement in ALSFRS-R compared to placebo.

• NurOwn treatment led to reductions in neurofilament light chain (NfL), a biomarker of neurodegeneration, and favorable shifts in inflammatory and neuroprotective biomarkers.

• Expanded Access Program data suggested improved survival and biomarker trends for patients continuing on NurOwn.

• Genotype analysis indicated a stronger response in certain genetic subgroups, particularly those with the AC variant of UNC13A.