The 201 Trial: a placebo-controlled randomized phase 2 study of safety and tolerance of the c-Abl kinase inhibitor risvodetinib in untreated Parkinson's disease

M H Werner¹, A McGarry^{2

3}, C Meyer⁴, E Mancino⁵, C Klint⁵, J Pellecchia⁵, K Kieburtz², T Levine⁶, B Bellaire⁶, C Gibbons^{6

7}, R Freeman⁶, A Ellenbogen⁸, K Klos⁹, M Ospina¹⁰, R A Hauser¹¹, K Shannon¹², H Asaad¹³, A Park¹⁴, P McAllister¹⁵, S H Isaacson¹⁶, M S LeDoux¹⁷, R Dhall¹⁸, D Shpiner¹⁹, P Charles²⁰, P Agarwal²¹, E Peckham²², P Mazzeo²³, M Davis²⁴, R Pahwa²⁵, M Brodsky²⁶, M Lew²⁷, L Purino²⁸, S Mantri²⁹, S Parashos³⁰, W Justiz³¹, M Chachar³², B Robottom³³, E Budman³⁴, K Blindauer³⁵, S Bellows³⁶, J Goudreau³⁷, S Steen³⁸, C W Olanow^{2

39}

Affiliations

¹ ABLi Therapeutics, Atlanta, GA, USA. mhwerner@ablitherapeutics.com.
² Clintrex Research, Sarasota, FL, USA.
³ Cooper Medical School at Rowan University/Cooper University Healthcare, Camden, NJ, USA.
⁴ ABLi Therapeutics, Atlanta, GA, USA.
⁵ Inhibikase Therapeutics, Atlanta, GA, USA.
⁶ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁷ CND Life Sciences, Scottsdale, AZ, USA.
⁸ QUEST Research Institute, Farmington, MI, USA.
⁹ The Movement Disorder Clinic of Oklahoma, Tulsa, OK, USA.
¹⁰ Clinical Endpoints, Scottsdale, AZ, USA.
¹¹ University of South Florida Health Byrd Institute, Tampa, FL, USA.
¹² University of Wisconsin-Madison, Madison, WI, USA.
¹³ Lone Star Neurology, Dallas, TX, USA.
¹⁴ Ohio State University College Of Medicine, Columbus, OH, USA.
¹⁵ Ki Health Partners, New Haven, CT, USA.
¹⁶ Parkinson's Disease and Movement Disorders Center, Boca Raton, FL, USA.
¹⁷ Veracity Neuroscience, Memphis, TN, USA.
¹⁸ University of Arkansas for Medical Sciences, Little Rock, AR, USA.
¹⁹ University of Miami, Miami, FL, USA.
²⁰ Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Evergreen Hospital Medical Center, Bellevue, WA, USA.
²² Central Texas Neurology Consultants, Round Rock, TX, USA.
²³ Coastal Neurology PA, Port Royal, SC, USA.
²⁴ Patient First MD, Middletown Township, NJ, USA.
²⁵ University of Kansas Medical Center Research Institute, Kansas City, KS, USA.
²⁶ Oregon Health & Science University, Portland, OR, USA.
²⁷ University of Southern California, Los Angeles, CA, USA.
²⁸ SC3 Research Group, Reseda, CA, USA.
²⁹ Duke Movement Disorders Clinic, Durham, NC, USA.
³⁰ Struthers Parkinson's Center, Golden Valley, MN, USA.
³¹ Aqualane Clinical Research, Naples, FL, USA.
³² Boston Neuro Research Center, North Dartmouth, MA, USA.
³³ Raleigh Neurology Associates, Raleigh, NC, USA.
³⁴ Neurology Center of New England, Foxborough, MA, USA.
³⁵ Medical College of Wisconsin, Milwaukee, WI, USA.
³⁶ Baylor College of Medicine, Houston, TX, USA.
³⁷ Michigan State University, Grand Rapids, MI, USA.
³⁸ Axiom Brain Health, Tampa, FL, USA.
³⁹ Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.

PMID: 41721133
DOI: 10.1038/s43587-026-01084-4

The 201 Trial: a placebo-controlled randomized phase 2 study of safety and tolerance of the c-Abl kinase inhibitor risvodetinib in untreated Parkinson's disease

M H Werner et al. Nat Aging. 2026.

. 2026 Feb 20.

doi: 10.1038/s43587-026-01084-4. Online ahead of print.

Authors

Affiliations

¹ ABLi Therapeutics, Atlanta, GA, USA. mhwerner@ablitherapeutics.com.
² Clintrex Research, Sarasota, FL, USA.
³ Cooper Medical School at Rowan University/Cooper University Healthcare, Camden, NJ, USA.
⁴ ABLi Therapeutics, Atlanta, GA, USA.
⁵ Inhibikase Therapeutics, Atlanta, GA, USA.
⁶ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁷ CND Life Sciences, Scottsdale, AZ, USA.
⁸ QUEST Research Institute, Farmington, MI, USA.
⁹ The Movement Disorder Clinic of Oklahoma, Tulsa, OK, USA.
¹⁰ Clinical Endpoints, Scottsdale, AZ, USA.
¹¹ University of South Florida Health Byrd Institute, Tampa, FL, USA.
¹² University of Wisconsin-Madison, Madison, WI, USA.
¹³ Lone Star Neurology, Dallas, TX, USA.
¹⁴ Ohio State University College Of Medicine, Columbus, OH, USA.
¹⁵ Ki Health Partners, New Haven, CT, USA.
¹⁶ Parkinson's Disease and Movement Disorders Center, Boca Raton, FL, USA.
¹⁷ Veracity Neuroscience, Memphis, TN, USA.
¹⁸ University of Arkansas for Medical Sciences, Little Rock, AR, USA.
¹⁹ University of Miami, Miami, FL, USA.
²⁰ Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Evergreen Hospital Medical Center, Bellevue, WA, USA.
²² Central Texas Neurology Consultants, Round Rock, TX, USA.
²³ Coastal Neurology PA, Port Royal, SC, USA.
²⁴ Patient First MD, Middletown Township, NJ, USA.
²⁵ University of Kansas Medical Center Research Institute, Kansas City, KS, USA.
²⁶ Oregon Health & Science University, Portland, OR, USA.
²⁷ University of Southern California, Los Angeles, CA, USA.
²⁸ SC3 Research Group, Reseda, CA, USA.
²⁹ Duke Movement Disorders Clinic, Durham, NC, USA.
³⁰ Struthers Parkinson's Center, Golden Valley, MN, USA.
³¹ Aqualane Clinical Research, Naples, FL, USA.
³² Boston Neuro Research Center, North Dartmouth, MA, USA.
³³ Raleigh Neurology Associates, Raleigh, NC, USA.
³⁴ Neurology Center of New England, Foxborough, MA, USA.
³⁵ Medical College of Wisconsin, Milwaukee, WI, USA.
³⁶ Baylor College of Medicine, Houston, TX, USA.
³⁷ Michigan State University, Grand Rapids, MI, USA.
³⁸ Axiom Brain Health, Tampa, FL, USA.
³⁹ Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.

PMID: 41721133
DOI: 10.1038/s43587-026-01084-4

Abstract

The nonreceptor Abelson (Abl) tyrosine kinases have been implicated as key drivers of initiation and progression in Parkinson's disease (PD). Risvodetinib, a potent, brain-penetrant, selective inhibitor of the nonreceptor Abl kinases c-Abl1 and c-Abl2/Arg (collectively, c-Abl), was evaluated in a randomized, double-blind, placebo-controlled phase 2a trial ('the 201 Trial') using once-daily 50 mg, 100 mg, 200 mg or placebo in 137 participants with early, untreated PD. The primary end points in safety and tolerability were met, with 95% of enrolled participants completing the 12-week dosing regimen and a 2-week safety follow-up. Both the average number of adverse events per person and the fraction of participants experiencing at least one treatment-emergent adverse event were similar between risvodetinib and placebo treatment groups, indicating that risvodetinib was safe and well tolerated. Although the trial was not powered to measure efficacy, 14 secondary end points evaluated motor and nonmotor features of disease in hierarchical order. The primary hierarchical secondary end point of the Movement Disorder Society revision to the Unified PD Rating Scale sum of Parts II + III did not reach statistical significance. The study findings indicate that risvodetinib is safe and well tolerated. Longer duration trials are needed to evaluate its potential clinical efficacy. ClinicalTrials.gov registration: NCT05424276 .

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Conflict of interest statement

Competing interests: M.H.W. is the Founder, was Chief Executive and remains a shareholder of Inhibikase Therapeutics, and is the Founder and a shareholder of ABLi Therapeutics. C.M., C.K. and J.P. are, or were, employees and shareholders of Inhibikase Therapeutics, and C.M. is a shareholder of ABLi Therapeutics. C.W.O is the past Chief Executive of Clintrex Research and K. Kieburtz is the current Managing Director of Clintrex. Clintrex Research provides services to many pharmaceutical and biotech companies, including Inhibikase and ABLi. C.W.O. was a shareholder of Inhibikase and served as an expert witness in the paraquat litigation. T.L. is Chief Medical Officer and shareholder of CND Life Sciences. R.F. is a shareholder of CND Life Sciences and Inhibikase Therapeutics, and was a board member of Inhibikase. C.G. is the Chief Scientific Officer of CND Life Sciences and is a shareholder. All other authors declare no competing interests.

References

1. Bach, J. P. et al. Projected numbers of people with movement disorders in the years 2030 and 2050. Mov. Disord. 26, 2286–2290 (2011). - PubMed - DOI
1. Pirooznia, S. K. et al. Parkinson disease: translating insights from molecular mechanisms to neuroprotection. Pharmacol Rev. 73, 33–97 (2021). - PubMed - DOI
1. Savitt, J. M. et al. Diagnosis and treatment of Parkinson disease: molecules to medicine. J. Clin. Invest. 116, 1744–1754 (2006). - PubMed - PMC - DOI
1. Jellinger, K. A. Neuropathology of sporadic PD: evaluation and changes of concepts. Mov. Disord. 27, 8–30 (2019). - DOI
1. Werner, M. H. & Olanow, C. W. PD modification through Abl kinase inhibition: an opportunity. Mov. Disord. 37, 6–15 (2022). - PubMed - DOI

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The 201 Trial: a placebo-controlled randomized phase 2 study of safety and tolerance of the c-Abl kinase inhibitor risvodetinib in untreated Parkinson's disease

Affiliations

The 201 Trial: a placebo-controlled randomized phase 2 study of safety and tolerance of the c-Abl kinase inhibitor risvodetinib in untreated Parkinson's disease

Authors

Affiliations

Abstract

Conflict of interest statement

References

Associated data

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous