Alumis has revealed encouraging results from a Phase I clinical trial of a selective tyrosine kinase 2 (TYK2) inhibitor, A-005, in healthy subjects.
The Phase I trial involved 135 healthy subjects and included various dosing cohorts to evaluate the drug’s effects over single and multiple doses. The trial also featured a lumbar puncture in one cohort to directly measure A-005 concentrations in the cerebral spinal fluid (CSF).
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For both the single-ascending dose (SAD) and multiple-ascending (MAD) portions of the trial, pharmacodynamic markers, including pSTAT levels, were measured.
The trial’s focus was on assessing the safety, pharmacokinetics (PK), and tolerability of single- and multiple-ascending doses of the therapy.
It demonstrated that the therapy had no serious adverse events and exhibited the potential for significant and prolonged exposure within the CSF. The therapy was well tolerated in the trial and showed the ability to cross the blood-brain barrier.
The levels of the therapy in the CSF were comparable to or exceeded those in plasma, surpassing the IC90 levels required for efficacy in cell-based assays.
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By GlobalDataA-005 displayed dose-proportional increases in drug exposure, with rapid attainment of peak drug concentration and half-lives extending up to 12 hours in the SAD cohorts.
A pharmacokinetic/pharmacodynamic (PK/PD) relationship was identified, demonstrating prolonged and maximal inhibition of TYK2 in the periphery.
This was measured by the levels of phosphorylated STAT proteins.
Alumis chief medical officer Jörn Drappa said: “A-005 is the first reported allosteric TYK2 inhibitor that has demonstrated the ability to cross the human blood-brain barrier to address inflammation within the central nervous system (CNS).
“Our Phase II clinical trial of ESK-001 in psoriasis demonstrated that maximal TYK2 inhibition was critical for increased clinical responses. Similarly, we hope to demonstrate that potent and selective target engagement of A-005 in the CNS leads to clinical benefit in MS, our first indication, and potentially in other neuroinflammatory and neurodegenerative conditions in the future.”
With these positive Phase I outcomes, Alumis is looking forward to progressing A-005 into a Phase II clinical trial for multiple sclerosis, which is anticipated to commence in the second half of the following year.
