Coya Therapeutics, Inc. announced successful meetings with the U.S. Food and Drug Administration following a pre-IND (Investigational New Drug) meeting and a Type C meeting intended to seek advice from the Agency to reach alignment on multiple aspects of the planned development program in support of an IND application of COYA 302 for the treatment of ALS. COYA 302 is a dual-mechanism investigational biologic combination therapy comprised of proprietary low dose IL-2 and fusion protein CTLA-4 Ig. Low dose IL-2 enhances anti-inflammatory Treg function and numbers while the fusion protein CTLA-4 Ig is intended to suppress pro-inflammatory cell function enabling potentially synergistic mechanisms in modulating inflammatory pathways.

As a result of the interactions with the FDA, Coya has obtained constructive feedback and has reached alignment on key areas involved in the development of COYA 302, including CMC (chemistry, manufacturing, and controls), preclinical and clinical activities for the IND application. The results of the regulatory meetings constitute a significant step towards the submission of the IND application to the FDA in the second quarter of 2024, and initiation of a well-controlled, double-blind clinical trial of COYA 302 in patients with ALS upon acceptance of the IND. Coya plans to continue working closely with the FDA over the course of the COYA 302 development program.

About COYA 302 COYA 302 is an investigational and proprietary biologic combination therapy with a dual immunomodulatory mechanism of action intended to enhance the anti-inflammatory function of regulatory T cells (Tregs) and suppress the inflammation produced by activated monocytes and macrophages. COYA 302 is comprised of proprietary low dose interleukin-2 (LD IL-2) and CTLA-4 Ig and is being developed for subcutaneous administration for the treatment of patients with ALS. These mechanisms may have additive or synergistic effects.

In February of 2023 Coya announced results from a proof-of-concept, open-label clinical study evaluating LD IL-2 and CTLA-4 Ig in small cohort of patients with ALS, conducted at the Houston Methodist Research Institute (Houston, Texas) by Stanley Appel, M.D., Jason Thonhoff, M.D., Ph.D., and David Beers, Ph.D. This study was the first-of-its-kind evaluating this dual-mechanism immunotherapy for the treatment of ALS. Patients in the study received investigational treatment for 48 consecutive weeks and were evaluated for safety and tolerability, Treg function, serum biomarkers of oxidative stress and inflammation, and clinical functioning as measured by the ALSFRS-R scale. During the 48-week treatment period, the therapy was well tolerated.

The most common adverse event was mild injection-site reactions. No patient discontinued the study, and no deaths or other serious adverse events were reported. Patients' disease progression was measured using the ALSFRS-R scale, a validated rating tool for monitoring the progression of disability in patients with ALS.

The mean (±SD) ALSFRS-R scores at week 24 (33.75 ±3.3) and week 48 (32 ±7.8) after initiation of treatment were not statistically different compared to the ALSFRS-R score at baseline (33.5 ±5.9), suggesting significant amelioration in the progression of the disease over the 48-week treatment period. Treg suppressive function, expressed as percentage of inhibition of proinflammatory T cell proliferation, showed a statistically significant increase over the course of the treatment period and was significantly reduced at the end of the 8-week washout post-treatment period. Treg suppressive function at 24 weeks (79.9±9.6) and 48 weeks (89.5±4.1) were significantly higher compared to baseline (62.1±8.1) (p<0.01), suggesting enhanced and durable Treg suppressive function over the course of treatment.

In contrast, Treg suppressive function (mean ±SD) was significantly decreased at the end of the 8-week washout period compared to end-of-treatment at week 48 (70.3±8.1 vs. 89.5±4.1, p <0.05). The study also evaluated serum biomarkers of inflammation, oxidative stress, and lipid peroxides.

The available data up to 16 weeks after initiation of treatment suggest a decrease of these biomarker levels, which is consistent with the observed enhancement of Treg function. The evaluation of the full biomarker data is ongoing. COYA 302 is an investigational product not yet approved by the FDA or any other regulatory agency.