Coya Therapeutics (COYA) investor relations material

Advances in ALS treatment and unmet needs

• Recent years have seen targeted therapies like tofersen for SOD1 ALS, demonstrating the potential to slow, halt, or even reverse disease progression, though this currently benefits only a small subset of patients.

• There is a significant unmet need for therapies that address the fundamental biology of ALS, beyond symptomatic management, to make a dramatic difference in patient outcomes.

• Decades of research have identified neuroinflammation, particularly involving regulatory T cells (Tregs) and activated macrophages, as central to ALS pathology.

Scientific rationale for combination therapy

• Dysfunctional Tregs in ALS fail to suppress neuroinflammation, contributing to disease progression.

• Laboratory findings show that activated macrophages can render Tregs dysfunctional, but this can be counteracted by abatacept (CTLA-4 Ig), suggesting a combination approach.

• Combining low-dose IL-2 (to expand Tregs) with CTLA-4 Ig (to suppress macrophage-driven inflammation) may offer a more effective therapeutic strategy.

Early clinical evidence and biomarker response

• A small study in four ALS patients using the IL-2/CTLA-4 combination showed slowed or halted disease progression over six months, with improvements in key biomarkers such as IL-18, oxidized LDL, 4-HNE, and NfL.

• These results, though from a limited sample, align with preclinical data and support advancing to larger trials.