risvodetinib (ABLi-148009) / Inhibikase, Clintrex, ABLi Therapeutics - LARVOL DELTA

ABLi Therapeutics…announces it has entered into a collaboration agreement with The Michael J. Fox Foundation for Parkinson’s Research (MJFF) to include ABLi’s lead candidate, risvodetinib, in the MJFF-sponsored Path to Prevention (P2P) platform trial (GlobeNewswire) - "The multi-arm P2P trial, expected to launch in the coming months, will investigate the safety and efficacy of several investigational agents in participants who have biomarker characteristics of Parkinson’s disease, also known as prodromal Parkinson’s disease, but have not yet progressed to a full diagnosis."

Commercial • New trial • Parkinson's Disease

IKT-148009, A NEXT-GENERATION C-ABL INHIBITOR, CONFERS NEUROPROTECTION IN MPTP MOUSE MODEL OF PARKINSON'S DISEASE (ADPD 2026) - "IkT-148009 selectively inhibits c-Abl activation and α-synuclein phosphorylation, protecting dopaminergic neurons and improving motor function in acute MPTP mice. These results support its potential as a disease-modifying therapy in Parkinson's disease."

Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • ABL1 • GFAP

EVALUATING MECHANISTIC AND TREATMENT OUTCOMES OF RISVODETINIB THROUGH BLOOD-BORNE AND TISSUE BIOMARKERS FROM THE 201 TRIAL IN UNTREATED PARKINSON'S DISEASE (ADPD 2026) - "Evaluation of pathway biomarkers may permit direct measurement of treatment effect in the clinical trial setting from blood and tissue biomarkers."

Biomarker • Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease • ABL1 • ABL2 • AIMP2 • L1CAM

SynuSight Biotech, ABLi Therapeutics and XingImaging Announce Strategic Collaboration to Implement Alpha-Synuclein PET Imaging into Clinical Trials Evaluating Risvodetinib as a Disease-modifying Therapy for Parkinson’s Disease (GlobeNewswire) - "SynuSight Biotech has licensed 18F-FD4 to XingImaging and to ABLi Therapeutics to evaluate alpha-synuclein clearance from the brain in response to risvodetinib treatment...ABLi plans to implement FD4 in two clinical trials in 2026...The first, ABILITY-PD, plans to re-enroll the 120 participants in the Phase 2a 201 Trial completed in 4Q24 to measure the effect of risvodetinib treatment on biomarkers from brain, blood and tissue in a 12-month longitudinal biomarker study....The second, the c-Abl inhibitor Modification of Parkinson’s Disease (CAMPD) trial, a Phase 2b/3 trial, will evaluate the efficacy of risvodetinib in a double-blind, placebo controlled trial in up to 500 participants with untreated Parkinson’s disease."

Commercial • Diagnostic • New P2/3 trial • Trial status • Parkinson's Disease

Comparative In silico evaluation of c-Abl inhibitors for Parkinson's disease therapy. (PubMed, Biochem Biophys Res Commun) - "Here, we performed a comparative in silico evaluation of five c-Abl inhibitors-Imatinib, Nilotinib, Ponatinib, Risvodetinib, and PD180970. The BBB permeability and toxicity analysis, using ADMETLab and DeepPK, predicted that PD180970 has enhanced blood-brain barrier permeability and a lower toxicity profile compared to the other inhibitors. Together, these integrated computational findings indicate PD180970 as a promising next-generation c-Abl inhibitor and support its prioritisation for further preclinical and clinical studies in PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • ABL1

IkT-148009-201: A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease (clinicaltrials.gov) - P2 | N=137 | Completed | Sponsor: ABLi Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

A Phase 2 Study of Risvodetinib in Untreated Parkinson's Disease (MDS Congress 2025) - P2 | "Risvodetinib met its primary endpoints and functional assessments trended toward clinical benefit supported by a direct effect of treatment on neuronal alpha-synuclein deposition."

P2 data • CNS Disorders • Movement Disorders • Parkinson's Disease • ABL1 • ABL2

The data were presented at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii, by Milton Werner, PhD, founder and CEO of ABLi Therapeutics. (NeurologyLive) - "The multicenter, double-blind, placebo-controlled 201 Trial (NCT05424276) evaluated 3 once-daily oral doses of risvodetinib—50 mg, 100 mg, and 200 mg—in individuals with early-stage PD who had not yet initiated dopaminergic therapy....Secondary efficacy outcomes assessed motor and nonmotor symptoms using a range of validated scales. Two measures—MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 2 and the Schwab and England Activities of Daily Living (SEADL) scale—reached nominal statistical significance at the 100-mg and 50-mg doses, respectively. An approximate dose-response trend was observed on Part 2 of the MDS-UPDRS. Across the 15 secondary outcome assessments, 13 showed a numerical trend favoring risvodetinib over placebo."

P2 data • Parkinson's Disease

ABLi Therapeutics to Present “Clinical Breakthrough Lecture” at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (GlobeNewswire) - "...the final results from the 201 Trial evaluating the safety and tolerability of risvodetinib in patients with untreated Parkinson’s disease (PD) will be presented....During the conference Dr. Werner will also present an electronic poster highlighting specific details of the 201 Trial and the measurement of new biomarkers that inform on the biochemical consequences of risvodetinib treatment, as well as biomarkers reporting on the underlying alpha-synuclein pathology of Parkinson’s disease."

P2 data • Parkinson's Disease

ABLi Therapeutics Announces Details of the End of Phase 2 Meeting with FDA for Evaluation of Risvodetinib as a Treatment for Parkinson’s Disease (GlobeNewswire) - "ABLi Therapeutics...completed an End of Phase 2 (EOP2) meeting with the Food and Drug Administration (FDA) to discuss outcomes of the 201 Trial in untreated Parkinson’s disease and to review plans for the Phase 3 program...The meeting’s primary purpose was to discuss endpoints to be used in a Phase 3 program and to define what tangential clinical and pre-clinical experiments may be necessary for a potential filing of a New Drug Application (NDA.) The Company presented data showing that the 201 Trial reached nominal significance for the Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and for the Schwab & England Activities of Daily Life (SEADL) scale in a 12 week treatment, which were consistent with the FDA’s preference for evaluating patient quality of life as a primary assessment of clinical benefit."

FDA event • New P3 trial • Trial status • Parkinson's Disease

ABLi Therapeutics Launches with a Focus on Developing Treatments for Neurodegenerative Diseases that Arise from Activation of c-Abl Kinases (GlobeNewswire) - "ABLi Therapeutics...launched today with the mission of developing its lead product candidate, Risvodetinib (ABLi-148009), as a potential disease-modifying therapy for Parkinson’s and Parkinson’s-related diseases and a portfolio of second-generation product candidates."

Pipeline update • Parkinson's Disease

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF RISVODETINIB, A SELECTIVE C-ABL INHIBITOR, IN UNTREATED PARKINSON'S DISEASE (ADPD 2025) - P2 | "Conclusions Formal Results of the study will be presented at the meeting. To date, IkT-148009 appears to be safe and well tolerated"

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease • ABL1 • ABL2

IkT-148009-201: A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: ABLi Therapeutics, Inc. | Trial completion date: Jan 2025 ➔ Jun 2025

Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Parkinson’s Disease New Drug Development Fails in Series… Inhibikase Discontinues ’Risvodetinib’ and Focuses on PAH [Gogole trnaslation] (The Bio) - P2 | N=120 | NCT05424276 | Sposnor: Inhibikase Therapeutics, Inc. | "On the 30th (local time), American pharmaceutical company Inhibikase Therapeutics...announced that it will discontinue the development of 'risvodetinib (development code name IkT-148009),' a new drug candidate for Parkinson's disease in phase 2 clinical trials. Instead, Inhibikase plans to focus on its other major development program, 'IkT-001Pro (development code name)...risbodetinib met the primary efficacy objectives in terms of safety and tolerability in the phase 2 clinical trial, but lacked the primary functional improvement effect. Inhibicase plans to present additional analysis results at a future academic conference...The clinical results showed that lisbodetinib showed a similar frequency and severity of side effects compared to the placebo group after 95% of participants completed the 12-week treatment, indicating no issues related to safety and tolerability."

Discontinued • P2 data • Parkinson's Disease • Pulmonary Arterial Hypertension

A PK Study of IkT-148009 in Older and Elderly Healthy Subjects (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Inhibikase Therapeutics, Inc.

New P1 trial

A Phase I 7-Day Dosing Study of IkT-148009. (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Inhibikase Therapeutics, Inc.

New P1 trial

The 201 Trial in Untreated Parkinson's Disease (MDS Congress 2024) - "Data from a 12 week double-blinded, placebo controlled trial will be presented providing a first look into whether a treatment validated in models of heritable and sporadic PD can impact disease in human Parkinson's."

CNS Disorders • Parkinson's Disease • ABL1

IkT-148009-201: A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Inhibikase Therapeutics, Inc. | Trial primary completion date: Jun 2024 ➔ Sep 2024

Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Inhibikase Therapeutics Reports Second Quarter Financial Results and Highlights Recent Period Activity (GlobeNewswire) - "'We completed enrollment of The 201 Trial evaluating risvo in untreated Parkinson’s disease, and anticipate the last patient exiting the study in September, 2024. We anticipate reporting topline data in November, 2024.'"

P2 data • Trial status • CNS Disorders • Parkinson's Disease

Inhibikase Therapeutics Completes Enrollment of the Phase 2 ‘201’ Trial Evaluating Risvodetinib in Untreated Parkinson’s Disease (GlobeNewswire) - "Inhibikase Therapeutics...announced the company has completed enrollment in the Phase 2 ‘201’ trial evaluating the safety and tolerability of risvodetinib ('risvo'), a potent selective c-Abl inhibitor, for treatment in untreated Parkinson’s patients. The company expects to report trial results in the fourth quarter of 2024....The trial has enrolled all 120 participants across 32 sites across the United States, and expects to randomize 126 patients total so as not to exclude already screened participants from participating in the trial."

Enrollment closed • P2 data • Parkinson's Disease

Inhibikase Therapeutics Announces Expansion to its Therapeutic Pipeline and Updates its Research and Development Programs (GlobeNewswire) - "Inhibikase Therapeutics, Inc...today announced expansion of its therapeutic pipeline and multiple updates to its Research and Development programs....The Company anticipates that the last patient will complete the 12-week treatment period before the close of the third quarter of 2024. The Company expects to report biomarker and outcome data to support the Company’s pursuit of an End of Phase 2 and Phase 3 protocol discussion with the FDA by the end of 2024."

FDA event • Trial status • CNS Disorders • Parkinson's Disease

A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Inhibikase Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease

Emerging Novel Therapies in Development for PD (NeurologyLive) - "Kremens gave thoughts on the use of several investigational continuous agents, including IPX203, risvodetinib, and P2B001."

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The 201 Trial in Untreated Parkinson's Disease (AAN 2024) - "Data from a 12 week double-blinded, placebo controlled trial will be presented providing a first look into whether a treatment validated in models of heritable and sporadic PD can impact disease in human Parkinson's."

Cardiovascular • CNS Disorders • Movement Disorders • Parkinson's Disease • ABL1

Inhibikase Therapeutics to Provide Trial Update for Risvodetinib at the 2024 International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (GlobeNewswire) - "Inhibikase Therapeutics, Inc...today announced that Dr. Milton Werner, President and Chief Executive Officer of Inhibikase Therapeutics, will present an update on the of the 201 Trial evaluating risvodetinib ('risvo') at the 2024 AD/PD Meeting being held March 5-9, 2024 in Lisbon, Portugal."

P2 data • CNS Disorders • Parkinson's Disease