COYA 302 Heads to Phase 2 Trial of ALS Following IND Acceptance

Arun Swaminathan

According to a recent announcement, the FDA has accepted the investigational new drug application (IND) for COYA 302 (Coya Therapeutics), a proprietary combination therapy of low dose interleukin-2 (LD IL-2), and CTLA-4 immunoglobulin, as a potential treatment for amyotrophic lateral sclerosis (ALS). Coya will now initiation a phase 2, multicenter, double-blind, placebo-controlled trial to further evaluate the agent’s efficacy and safety.¹

Details of the phase 2 study, shared previously in 2023, show a traditional double-blind study, with a 4-week screening period, 24-week treatment period, and 4-week safety follow-up. A total of 120 patients will be randomized to either COYA 302 or placebo, with combined assessment of function and survival (CAFS) as the primary end point. Overall, the trial will test efficacy, safety an tolerability, biological activity, and biomarkers of ALS progression.²

"The FDA's acceptance of this IND marks a pivotal moment in Coya's journey. We are now preparing to initiate a well-powered, well-controlled, multicenter Phase 2 study to evaluate the efficacy and safety of COYA 302 in patients with ALS," Arun Swaminathan, chief executive officer at Coya, said in a statement.¹ "We are grateful to the ALS community for their continued support of this important program."

An investigational agent, COYA 302 is designed to restore/boost regulatory T cells (Tregs) and dial down pro-inflammatory T-cell/myeloid activity that tracks with faster ALS progression. Previous research has shown that Tregs are reduced or dysfunctional in ALS and their function inversely correlates with disease severity and rate of decline.³ In addition, adaptive immunity and myeloid activation contribute to progression, supporting immune modulation as a viable therapeutic angle.

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The anticipated phase 2 trial will include patients with ALS, both sporadic and familial forms, who’ve had ALS symptom onset for less than 24 months. Inclusion criteria also states patients must have an ALS Functional Rating Scale-Revised (ALSFRS-R) score of at least 35 at screening, a score of at least 2 points on each ALSFRS-R item, and a forced vital capacity (FVC) of at least 70% of predicted capacity for age, height, and gender at screening.

COYA 302 was previously tested in a phase 1, small-scale, open-label study of 4 patients with ALS, with results published in Frontiers Neurology in 2024. In the study, participants received subcutaneous injections of CTLA4-Ig (125 mg/mL/injection) every 2 weeks coinciding with the first IL-2 injection of each treatment cycle. Patients received a total of 24 treatment cycles during the first 48 weeks of the 56-week study, with disease progression monitored through ALSFRS-R.⁴

During the first 24 weeks, the average ALSFRS-R slope was +0.04 points/month, and over 48 weeks it was −0.13 points/month, with one participant improving by 0.9 points/month and the other three declining by an average of −0.47 points/month, a slower rate than the pre-therapy average decline of −1.1 points/month. Overall, Treg suppressive function and numbers increased during treatment, with biomarker responses in the first 16 weeks coinciding with minimal clinical progression.

Additional data from the phase 1 study showed mean decreases of 30% in 4-HNE levels, 19% decrease in ox-LDL, and 23% attenuation in IL-18. The suppression of 4-HNE, ox-LDL, and IL-18 occurred early in the treatment course, and neurofilament light, a well-accepted marker of neuronal structural degeneration, was also suppressed early. Suppression of these markers was associated with relatively stable disease for at least 24 weeks in all participants. Notably, the phase 1 study provided evidence that oxidative stress and inflammation may be differentially express in patients with ALS.

REFERENCES
1. Coya Therapeutics Announces FDA Acceptance of Investigational New Drug (IND) Application for COYA 302 for the Treatment of Amyotrophic Lateral Sclerosis (ALS). News release. Coya Therapeutics. August 25, 2025. Accessed August 25, 2025. https://www.prnewswire.com/news-releases/coya-therapeutics-announces-fda-acceptance-of-investigational-new-drug-ind-application-for-coya-302-for-the-treatment-of-amyotrophic-lateral-sclerosis-als-302537194.html
2. Unleashing the Power of Tregs. Coya Therapeutics. April 2023. Accessed August 25, 2025. https://s201.q4cdn.com/307844724/files/doc_presentations/2023/04/Coya-Therapeutics-Non_Confidential-Presentation-April-2023.pdf
3. Sheean RK, McKay FC, Cretney E, et al. Association of Regulatory T-Cell Expansion With Progression of Amyotrophic Lateral Sclerosis: A Study of Humans and a Transgenic Mouse Model. JAMA Neurol. 2018;75(6):681-689. doi:10.1001/jamaneurol.2018.0035
4. Thonhoff JR, Beers DR, Zhao W, et al. A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis. Front Neurol. 2024;15. doi:10.3389/fneur.2024.1415106