IKT’s proprietary Re-engineering Approach with Metabolism Preserved (RAMP™) drug innovation engine enables us to design and develop new chemical entities that draw on clinical experience to preserve the desired properties of template kinase inhibitor while ameliorating undesired properties, such as toxicity.

The company selects clinically validated kinase inhibitors as templates. From these templates, it seeks to create novel drugs with enhanced penetration into the brain, with potentially higher potency against the target and improved safety, to treat neurological and non-neurological diseases in which kinase activation is implicated. They are designed to be administered chronically and systemically.

Inhibikase Therapeutics’ first product candidates were generated using the company’s Re-engineering Approach with Metabolism Preserved (RAMP™) drug innovation engine use the same targeting strategy—blocking the activation of Abl kinases—as the basis for small-molecule medications capable of halting the progression of diseases across the therapeutic landscape.

Risvodetinib (IkT-148009), is a potent, selective small-molecule medication designed and engineered as chronically administered, once-daily oral medication targeting the underlying biological mechanism resulting in Parkinson’s disease, with the goal of halting disease progression and reversing functional loss. 

Parkinson’s patients have a series of disorders that may represent the earliest manifestations of the disease. These include difficulty in swallowing (dysphagia) and difficulty passing solid waste (neurogenic constipation), both due to a loss of the neurons necessary for these functions to occur on their own. 

IKT believes that its recent analysis of GI functional disorders in preclinical animal models with its lead product candidate for Parkinson’s, Risvodetinib (IkT-148009), suggests that the company can halt the progression of neurodegeneration in the GI tract and restore the functional loss.

Having demonstrated that Abl kinase inhibition can protect against disruption of development and progression of Parkinson’s-like disease in the brain and GI tract of validated animal models, the company has submitted two Investigational New Drug (IND) applications in February, 2019 to begin clinical development in multiple classes of Parkinson’s patients. Clinical development should proceed through 2024.

This study investigates the safety and tolerability of drug IkT-148009 in untreated Parkinson's disease volunteers (30 to 80 years old). It also looks at the pharmacokinetics of IkT-148009 in the body and evaluates the effect of risvodetinib on motor and non-motor features of the disease. This 12 week study is designed to be 3:1 randomized across 3 doses of risvodetinib or placebo. Each participant will self-administer one of 3 doses or placebo of risvodetinib once daily (QD) with food for 12 weeks. For more information, visit website: www.the201trial.com

This is a 12-Week, randomized, double-blind, multi-center, placebo-controlled dose-ranging clinical trial of three risvodetinib doses in patients with untreated PD designed to assess safety, tolerability, and pharmacokinetics of risvodetinib, an oral, once daily c-Abl tyrosine kinase inhibitor. Secondary and exploratory assessments will evaluate the effect of IkT-148009 on motor and non-motor features of the disease. 120 participants are anticipated to be enrolled at up to 34 sites across the US.

As of January 30th, 2024, 32 sites are open and actively evaluating prospective trial participants. 49 participants have been enrolled, 20 prospective participants are in medical screening and 52 potential participants are being evaluated for suitability to initiate medical screening.

The 201 Trial patient portal (www.the201trial.com) has been visited by more than 20,000 unique people since launch in September, 2023. The pre-qualification process has led to more than 250 unique individuals to contact open clinical sites, the first step in the evaluation process that could lead to enrollment. Monthly site enrollments have increased month-over-month since this patient outreach program was initiated.

In August 2023, unblinded functional assessments of 11 patients with untreated Parkinson’s disease were presented at the Movement Disorder Congress in Copenhagen, Denmark. These participants were withdrawn from the trial following the FDA’s temporary clinical hold in November, 2022, which was lifted January, 2023. 

These assessments showed that patients receiving the 200 mg dose of risvodetinib (N=3) saw a greater than 10 point improvement over placebo in the sum of motor and non-motor scores after once daily treatment for up to 11 weeks; by contrast, a typical patient with Parkinson’s disease would worsen by 3 to 6 points in the sum of motor and non-motor score assessments over a 12 month period. 

While the number of treated participants is too small for the Company to conclude a clinical benefit, these early data are cautiously encouraging.

In October 2023, risvodetinib was granted Orphan Drug Designation by the FDA for the treatment of MSA. In animal model studies of MSA, risvodetinib was shown to be therapeutically active. 

The designation by the FDA underscores the need for innovative treatment options for patients afflicted with this rare and rapidly progressing Parkinson’s-related disorder. 

The Company is pursuing a comparable designation in the European Union, or E.U., as part of its efforts to initiate a Phase 2 clinical trial to evaluate risvodetinib in MSA. The Company is discussing conduct of the trial with private foundations, Federal and industry stakeholders in an effort to initiate this trial in the future.

IkT-001Pro for  Chronic Myeloid Leukemia (CML): A New and Improved, Safer Alternative to Imatinib

IKT has developed IkT-001Pro as an outgrowth of its efforts to improve the safety of the first FDA-approved Abl kinase inhibitor, imatinib (marketed as Gleevec®)!

Imatinib is commonly taken for hematological cancers that arise from Abl kinase mutations in the bone marrow or for gastrointestinal cancers that arise from c-Kit mutations in the stomach.

• IkT-001Pro has shown to be potentially as much as three times safer than imatinib in non-human primates, blunting gastrointestinal side effects of imatinib therapy that occur following oral administration. Removing these gastrointestinal side effects has the potential to significantly improve the number of patients that reach and sustain complete cytogenetic response in stable-phase chronic myelogenous leukemia (CML). IKT believes that removing these side effects will also improve patient adherence to daily therapy and improve patients' quality of life while on therapy.
• IkT-001Pro has received Orphan Drug Designation for stable-phase CML and will follow the development pathway for approval through the 505(b)(2) regulation. This pathway would allow the company to rely, in part, on data in the public domain or the FDA’s prior conclusions regarding the safety and effectiveness of an approved compound.
• The company’s completed ‘501’ study has identified the doses of IkT-001Pro that reaches the same exposure as the approved doses of 400 mg and 600 mg imatinib mesylate and has demonstrated that there were minimal adverse events observed at all doses. The company believes that this data supports the potential approval of IkT-001Pro with blood or stomach cancers, similar to the adult indications for imatinib mesylate.
• The company was granted a pre-New Drug Application (pre-NDA) meeting that was held with the FDA review team in January 2024 to discuss the requirements for approval of IkT-001Pro and to review the data establishing doses of IkT-001Pro the Company believes are bioequivalent to 400 mg and 600 mg imatinib mesylate.

• Multi-therapeutic pipeline across neurodegenerative disease, cancer, and infectious disease.
• Risvodetinib (IkT-148009): Lead Selective Abelson Tyrosine Kinase (c-Abl) inhibitor with potential to be a disease-modifying treatment for Parkinson’s disease (PD) and related disorders. Phase 2, 201 trial ongoing with nearly all sites open, approximately 41% enrolled in the U.S. The 201 trial planned to be expanded for 12 additional months providing 15 months of data to evaluate clinical benefit.
• IkT-001Pro: Prodrug of imatinib mesylate with improved safety/tolerability profile for the treatment of stable-phase chronic myelogenous leukemia (CML). Bioequivalent 501 trial completed and FDA pre-NDA meeting January 2024 to discuss approval for 8 adult indications under 505(b)(2).
• Robust patent portfolio with protection to 2033 (oncology) and 2036 (neurodegeneration). Orphan designations: Rivsodetinib in Multiple System Atrophy, IkT-001Pro in up to 8 oncology indications.
• Cash/cash equivalent runway into 4Q24. Continue to seek non-dilutive capital through Federal Government and private foundation sources.
• Highly experienced management team, consultants, Board of Directors, and Scientific Advisory Board.

Inhibikase Therapeutics, Inc. (Nasdaq: IKT) is a clinical-stage pharmaceutical company developing therapeutics for Parkinson's disease and related disorders. 

The company’s multi-therapeutic pipeline focuses on neurodegeneration and its lead program for Risvodetinib, an Abelson Tyrosine Kinase (c-Abl) inhibitor, targets the treatment of Parkinson's disease inside and outside the brain as well as other diseases that arise from Abelson Tyrosine Kinases. 

Its multi-therapeutic pipeline is pursuing Parkinson's-related disorders of the brain and GI tract, orphan indications related to Parkinson's disease such as Multiple System Atrophy, and drug delivery technologies for kinase inhibitors such as IkT-001Pro, a prodrug of the anticancer agent imatinib mesylate that the Company believes will provide a better patient experience with fewer on-dosing side-effects. 

The Company's RAMP™ medicinal chemistry program has also identified a number of follow-on compounds to IkT-148009 to be potentially applied to other cognitive and motor function diseases of the brain.

There's currently no cure for Parkinson's disease, but treatments are able to relieve the symptoms helping patients maintain a quality of life. IKT’s novel treatments could give hope to many Parkinson’s Disease patients around the world!

Large companies such as pharma giants Merck & Co (NYSE: MRK), Roche (ROG: SIX), Novartis (NOVN: VX), and AbbVie (NYSE: ABBV) are showing greater interest in Parkinson’s Disease treatments.

IKT is anticipating results from its  201 trial may be available in the second half of 2024 and is continuing its efforts to complete the requirements for FDA approval of IkT-001Pro!