Coya Therapeutics (COYA) Status update summary

Advances in ALS and Neurodegenerative Disease Treatment

• Targeted therapies like tofersen for SOD1 ALS and novel Treg-directed combinations show potential to slow or halt disease progression, though current benefits are limited to subsets of patients.

• There is a significant unmet need for therapies that address the fundamental biology of ALS and related neurodegenerative diseases, beyond symptomatic management.

• Decades of research highlight neuroinflammation, especially involving Tregs and activated macrophages, as central to ALS pathology.

• Market opportunity for these therapies exceeds $10B across ALS, FTD, AD, and PD indications.

• Strong partnerships, including Dr. Reddy's with up to $700M in milestones and $47M cash runway into 2H 2027, support development.

Scientific Rationale and Clinical Validation

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

• Activated macrophages can render Tregs dysfunctional, but this can be counteracted by abatacept (CTLA-4 Ig), supporting 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 trials show improved or stabilized ALSFRS-R scores and cognitive stability in FTD, with enhanced Treg function and reduced pro-inflammatory markers.

• Low-dose IL-2 and CTLA-4 Ig combination is well-tolerated with no serious adverse events in early studies.

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.

• Preclinical and clinical data support enhanced Treg function and reduced pro-inflammatory markers.