Yumanity Shares Update on Potential Treatment YTX-7739

YTX-7739, a potential disease-modifying therapy for Parkinson’s disease, was safe, well-tolerated, and found to have a favorable pharmacological profile when given to a group of healthy volunteers.

Yumanity Therapeutics provided those early findings from a recently completed single ascending-dose (SAD) Phase 1 clinical trial.

Based on the results, Yumanity will continue to explore YTX-7739’s safety and tolerability in healthy volunteers in its multiple ascending-dose (MAD) Phase 1 study. With participant enrollment now complete, Yumanity anticipates announcing data from the study in the coming months.

In the meantime, the company has launched a placebo-controlled, Phase 1b trial that will assess the safety and pharmacological properties of multiple increasing doses of YTX-7739 in about 30 people with Parkinson’s. Dosing has already begun and preliminary data is expected by mid-year.

“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. 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,” Brigitte Robertson, MD, chief medical officer at Yumanity Therapeutics, said in a press release. 

“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,” Robertson said.

YTX-7739 is a small molecule inhibitor of stearoyl-CoA desaturase (SCD), an enzyme that produces certain fatty molecules that are thought to mediate the neurotoxic effects of alpha-synuclein — the protein that accumulates inside nerve cells over the course of Parkinson’s to the point where it becomes toxic, causing them to die.

YTX-7739 is small enough that it can cross the blood-brain barrier, which is the semi-permeable barrier that separates the brain from the blood circulating in the rest of the body. By blocking the activity of SCD, YTX-7739 is expected to interfere with the signaling cascade underlying the harmful neurotoxic effects of alpha-synuclein in brain cells.

“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 stearoyl-CoA desaturase (SCD) could overcome alpha-synuclein toxicity, suggesting its potential as a therapeutic target,” said Robert Scannevin, PhD, head of discovery at Yumanity Therapeutics.

Previous preclinical findings showed that YTX-7739 was able to protect nerve cells against the neurotoxic effects of alpha-synuclein and prolong their survival.

Following these promising early findings, Yumanity launched a Phase 1 trial to assess the safety, tolerability, and pharmacological properties of YTX-7739 in a group of healthy volunteers.

The study enrolled a total of 56 healthy volunteers (22 men and 34 women), ages 19–39, who received a single oral dose (ranging from 5 to 400 mg) of YTX-7739. From these, 40 participated in the double-blind, placebo-controlled portion of the study, where they were assigned randomly to receive either YTX-7739 or a matched placebo.

The study also included two groups (of eight participants each) that were given YTX-7739 with meals, as well as two additional groups (of eight participants each) in which treatment was given following an open-label regimen (participants were aware of the treatment they were receiving.) That information was used to further assist in the selection of the therapy’s dosages in future studies.

Data from the study just announced by Yumanity show YTX-7739 was safe and well-tolerated, with most reported side effects being either mild or moderate in severity.

Additional analyses also showed that when given with food, YTX-7739 had a pharmacological profile that was compatible with a low daily dose mode of administration. The concentration that the medication reached in the blood of study participants exceeded the levels that were estimated to be needed to ensure YTX-7739 interacted with its intended target.

As in previous preclinical studies, YTX-7739 also achieved clinically relevant concentrations in the participants’ cerebrospinal spinal fluid (CSF, the liquid that surrounds the brain and spinal cord).

Data from this study supported the launch of another randomized, double-blind, placebo-controlled, Phase 1 trial, which is evaluating the safety, tolerability, and pharmacological properties of a once-daily treatment regimen of YTX-7739 (given at a dose of 15 or 25 mg), lasting 14–28 days, in a group of 16 healthy volunteers. During the study, investigators also will measure the levels of certain biomarkers of pharmacological activity in the blood and spinal fluid of study participants.

The placebo-controlled Phase 1b study in patients with Parkinson’s disease will further evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of multiple ascending doses of YTX-7739’s. Researchers also will assess potential biomarkers of SCD activity and YTX-7739′s concentration in the CSF, blood, and other fluids or tissues. Of note, pharmacokinetics refers to how a medication moves through and is processed by the body, while pharmacodynamics refers to the interactions between the body and a compound.

The company is planning to present detailed findings from these Phase 1 studies in healthy volunteers at future medical meetings.