Application of RAMP™ Drug Innovation Engine

Small-molecule Medications with World-class Potential

Inhibikase Therapeutics’ first product candidates were generated using our 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 progression of diseases across the therapeutic landscape:

  • A disease-modifying therapy that we believe halts the progression and reverses the functional loss arising from Parkinson’s disease in the brain and gastrointestinal (GI) tract while simultaneously reducing or clearing the toxic form of alpha-synuclein believed to be the cause of Parkinson’s.
  • A treatment for stable-phase Chronic Myelogenous Leukemia (CML) with a prodrug of the anticancer agent imatinib that we believe will have a superior safety profile, improve oral absorption, lower the dose required for efficacy and suppress ongoing nausea, diarrhea, and vomiting associated with imatinib therapy.
  • A companion therapeutic that we believe may remove the risk of JC polyomavirus (JCV) infection in the brain, the cause of Progressive Multifocal Leukoencephalopathy (PML). PML is a rare but rapidly fatal brain infection that arises from the migration of JCV from reservoirs in the body into the brain. The development of PML has been linked to treatment with more than 15 immunosupressive medications that are used to treat cancer and autoimmune diseases, such as multiple sclerosis.
  • We are also exploring development opportunities for the treatment of Multiple System Atrophy (MSA) and Dementia with Lewy Body (DLB). MSA is a neurodegenerative movement disorder which shares the hallmarks of c-Abl activation and alpha-synuclein chemical modification with Parkinson’s Disease, but arises in a different area of the brain than Parkinson’s itself. DLB is a Parkinson’s-like disease characterized by a primary cognitive deficit that arises from alpha-synuclein aggregate formation.

Abl Kinases and CNS Diseases

Abl kinases have been shown to play a critical role in monitoring insults to brain neurons and regulating biological pathways associated with neuroprotection. In addition, recent research has demonstrated that Abl kinases are essential checkpoint regulators that play a central role in Parkinson’s disease initiation and progression.

The breakthrough cancer treatment, imatinib (Gleevec®), was the first FDA-approved Abl kinase inhibitor. Because of the way imatinib is broken down in the body, imatinib’s safety is correlated with dose.

Applying our RAMP technology to imatinib, Inhibikase has generated novel chemical entities that have:

  • Up to 25-fold enhanced potency against wildtype c-Abl.
  • Selectivity for non-receptor Abelson tyrosine kinases, resulting in a better safety and toxicology profile compared to other drugs in this class.
  • Nearly identical route of metabolism to imatinib, thereby preserving the relationship between administered dose, drug safety and frequency and type of adverse events.

We believe these molecules have the potential to enable dose reduction with a concomitantly improved safety profile, resulting in a safer Abl kinase inhibitor that may be chronically and systemically administered for the treatment of our target CNS indications.

Abl Kinases and Autonomic Nervous System Diseases

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

RAMP™ Drug Innovation Engine

We are advancing a new class of small-molecule product candidates using our Re-engineering Approach with Metabolism Preserved (RAMP™) drug innovation engine that targets specific protein kinases to treat neurodegenerative diseases.

About RAMP™ Drug Innovation Engine

Our Scientific Publications

We have a few publications accessible regarding various topics, including progressive multifocal leukoencephalopathy (PML), Parkinson’s disease, and other applications in infectious diseases.

View Publications