After results indicated significant slowing of ALS disease progression, Coya noted it plans to file an IND with the FDA in the second half of 2023 for a potential clinical study thereafter.
New data from a proof-of-concept study assessing Coya Therapeutics’ investigational agent COYA 302 showed that over a 48-week treatment period, patients with amyotrophic lateral sclerosis (ALS) showed amelioration in the progression of their disease. The therapeutic, designed to enhance proinflammatory T lymphocytes (Treg), successfully increased Treg suppressive function and was safe throughout the study.
In a cohort of 4 patients with ALS, the mean ALS Functional Rating Scale-Revised (ALSFRS-R) scores at week 24 (33.75 [±3.3) and week 48 (32.00 [±7.8]) were not statistically different to those observed at baseline (33.5 [±5.9]). Presented at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 19-22, in Dallas, Texas, the study reported no discontinuations, no deaths or serious adverse events (AEs), with mild injection site reactions as the most common AE observed.
COYA 302 is a combination of 2 biologics with a dual mechanism of action, synergistically enhancing Treg function and depleting effector T cells, activated macrophages, and pro-inflammatory cytokines to further decrease inflammation. One of the many products in development by Coya, COYA 302 includes COYA 301 as part of its mechanism of action. This Treg-enhancing biologic therapy plays a key role in the development, expansion, activity, and survival of Tregs.
In a statement, Stanley Appel, MD, chair of Coya’s Scientific Advisory Board, said, "Our study with a combination of IL-2 and CTLA4-Ig provided promising results. The therapy was well tolerated, and most significantly it enhanced regulatory T lymphocytes suppressive functions, suppressed markers of oxidative stress, and ameliorated disease progression over 48 weeks. The average patient decline, as measured by ALSFRS-R, is approximately -1-point/month."
Appel, the Peggy and Gary Edwards Distinguished Chair in ALS research, co-director of the Houston Methodist Neurological Institute, Chair of the Stanley H. Appel Department of Neurology, Houston Methodist Hospital, and professor of neurology at Weill Cornell Medical College, added “In the present study there was no average decline from baseline to 24 weeks and we observed minimal average decline from baseline to 48 weeks, suggesting that IL-2 and CTLA4-Ig may provide a potentially meaningful approach for the 'unmet need' in ALS."
The cohort of patients came into the study with a mean decline of 1.1 points/month on ALSFRS-R, and were followed for 48 weeks of treatment with an additional 8-week washout period to conclude the study. Findings showed that Treg suppressive function, expressed as a percentage of inhibition of proinflammatory T cell proliferation, was significantly higher at weeks 24 (79.9 [±9.6]) and 48 (89.5 [±4.1]) than baseline (62.1 [±8.1]; P <.01). These significant effects were seen through the end of the 8-week washout period. In contrast, investigators also observed significantly decreased Treg suppressive function at the end of the 8-week washout period as compared with week 48 (70.3 [±8.1] vs 89.5 [±4.1]; P <.05).
Although analyses are ongoing, data from up to 16 weeks showed decrease in serum biomarkers of inflammation, oxidative stress, and lipid peroxides, which was consistent with the observed enhancement of Treg function.
"We believe the results of this initial proof-of-concept study in a small number of ALS patients are encouraging and warrant conducting a larger and controlled industry-sponsored study. ALS continues to be a disease of high unmet need and we are committed to develop COYA 302 as safely and as expeditiously as possible, in compliance with current regulations," Adrian Hepner, MD, chief medical officer, Coya, said in a statement. "We plan to file an IND with the FDA in the second half of 2023 and initiate a clinical study soon thereafter."
Recently, Appel sat down with NeurologyLive® to discuss previously approved therapies for ALS, and whether they can synergistically work with agents that enhance T cells function. In the video below, Appel provided insight on the differences in each medication, and the role of Treg dysfunction in ALS research.