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Additionally, the therapy’s developer Yumanity Therapeutics announced the results of a single ascending dose study and enrollment in a multiple ascending dose study.
Yumanity Therapeutics recently announced several updates related to its lead clinical-stage therapeutic development program for its investigational Parkinson disease agent, YTX-7739, including the results of a single ascending dose study, the completion of enrollment in a multiple ascending dose study, and the initiation of a phase 1b study.
YTX-7739 is a small molecule stearoyl-CoA desaturase (SCD) inhibitor that is designed to modulate an upstream process in the alpha-synuclein pathological cascade. According to Yumanity, it has been shown to rescue or prevent toxicity in preclinical models, giving the company reason to assess the potential utility of YTX-7739 in Parkinson disease.
“YTX-7739 is a novel small molecule SCD inhibitor, which can be administered orally and was shown to be brain penetrant in preclinical models. We have completed the single ascending dose (SAD) study in healthy volunteers, which provides early evidence of the drug candidate’s safety and tolerability profile,” Brigitte Robertson, MD, chief medical officer, Yumanity Therapeutics, said in a statement. “We look forward to reporting on the data from the ongoing Multiple Ascending dose (MAD) study in healthy volunteers and the preliminary results of our first clinical trial in patients with Parkinson’s disease, later this year. We wish to also thank our investigators, their staff, study volunteers and patients for their dedication in continuing this important research through the challenges of the COVID-19 pandemic.”
Yumanity announced the initiation of a placebo-controlled, randomized, double-blind, MAD phase 1b study of YTX-7739 in patients with Parkinson disease.
That study is anticipated to include 30 individuals and will assess the safety and tolerability of the therapy, as well as pharmacokinetic and pharmacodynamic parameters including potential biomarkers of SCD activity and target engagement in the CSF, plasma, and other fluids or tissues. The preliminary results of the phase 1b study are expected to read out by mid-year 2021.
The phase 1 SAD study of YTX-7739 included 56 healthy volunteers aged 19 to 39 years (male, n = 22; female, n = 34) who were administered single doses of the agent ranging from 5 mg to 400 mg. The results of the SAD study supported progression to the MAD study.
Of those in the SAD study, 40 participated in the placebo-controlled, randomized, double-blind portion of the study, which consisted of 7 cohorts with 8 subjects each, randomized to either YTX-7739 or placebo in a 6:2 ratio. Two of those cohorts, including 16 patients, featured administration of YTX-7739 with food. Additionally, 2 cohorts of 8 subjects each were included in an open-label fashion to further inform dose selection for the MAD study.
Ultimately, the SAD study identified no safety concerns, and the Yumanity therapy was considered well-tolerated. Most adverse events (AEs) were deemed mild or moderate in severity. In tandem with a favorable pharmacokinetic profile in the fed state, the half-life of the therapy supports the notion that low daily doses administered with food can sustain the targeted range of drug exposure.
As well, plasma concentrations in the study exceeded levels of exposure that are estimated to be sufficient for target engagement based on the pharmacodynamic modeling. Consistent with prior preclinical data, YTX-7739 also showed clinically relevant drug concentrations in the cerebral spinal fluid (CSF).
The phase 1 MAD study is a placebo-controlled, randomized, double-blind study that is set to assess the safety, tolerability, and pharmacokinetics of once-daily oral administration of 2 doses of YTX-7739: 15 mg and 25 mg. The therapy will be given over the course of 14 to 28 days in 16 healthy male and female volunteers. The study is also evaluating measurements of plasma and CSF biomarker levels to assess pharmacodynamic activity.
Similar to the SAD study, it includes 2 cohorts of 8 subjects each, randomized to treatment or placebo in a 6:2 ratio. Yumanity noted that it anticipates the reporting of the results of the MAD study by the end of Q1 2021, with detailed clinical data from the phase 1 studies in healthy volunteers with YTX-7739 planned to be presented at a future medical conference.
“Recent advances in our understanding of the pathological processes underlying neurodegenerative diseases are providing the opportunities for innovative companies such as Yumanity to address this challenge with therapies that attack known disease pathways,” said Robert Scannevin, PhD, head of Discovery, Yumanity Therapeutics, in a statement. “Multiple lines of evidence indicate that misfolded alpha-synuclein is a strong risk factor for Parkinson’s disease. However, rather than targeting alpha-synuclein directly, we discovered that inhibiting the enzyme SCD could overcome alpha-synuclein toxicity, suggesting its potential as a therapeutic target.”