Clene (CLNN) investor relations material

Strategic focus and disease context

• Current focus is exclusively on ALS, a rapidly fatal neurodegenerative disease with high unmet need.

• ALS diagnosis is often delayed, worsening patient outcomes due to the disease's aggressive progression.

• No cure exists for ALS, and the burden on patients and families remains extremely high.

• The therapeutic approach centers on a gold nanocrystal suspension designed to enhance cellular energy and protect neuron function.

• The asset aims to restore mitochondrial function and reduce reactive oxygen species, supporting neuron health.

Clinical development and regulatory engagement

• The New Drug Application (NDA) is anchored on neurofilament light as a biomarker, which is measurable in blood and CSF.

• Regulatory precedent exists for neurofilament as a surrogate endpoint in ALS, supporting accelerated approval.

• Five Type C meetings with the FDA have shaped the NDA, focusing on three main programs: HEALEY phase II, RESCUE phase II, and expanded access funded by the ACT for ALS Act.

• The HEALEY program showed a statistically significant 10% reduction in neurofilament and a 94% risk reduction in survival as a secondary endpoint.

• The primary endpoint (ALSFRS) was not met, consistent with historical challenges in ALS trials.

Efficacy and biomarker validation

• Both HEALEY and expanded access programs demonstrated similar neurofilament reductions, even in more advanced patient populations.

• Survival benefit was observed in neurofilament-responsive individuals, with a 52% reduction in HEALEY and 76% in RESCUE.

• Functional benefits included statistically significant delays in clinical worsening and improvements in ALSFRS and slow vital capacity (SVC) among neurofilament responders.

• Randomization-based causal analysis further supported the link between neurofilament response and clinical benefit, with strong statistical significance.

• Over 1,250 patient-years of exposure have shown no serious adverse events related to the drug.