Yumanity Therapeutics Announces Study Demonstrating In Vivo Efficacy of YTX-7739 in a Glioblastoma Multiforme (GBM) Mouse Model

Yumanity Therapeutics recently announced results of a study that demonstrate in vivo efficacy, including increased median overall survival, of YTX-7739 in a mouse model for glioblastoma multiforme (GBM). The study was conducted by researchers at the Massachusetts General Hospital and is being presented virtually today at the Society for NeuroOncology/National Cancer Institute (SNO/NCI) Joint Symposium: Targeting CNS Tumor Metabolism. YTX-7739 is currently in clinical development by Yumanity Therapeutics as a potential treatment for Parkinson’s disease.

The research entitled, Targeting Fatty Acid Biosynthesis in Glioblastoma, was conducted in the laboratory of Christian E. Badr, PhD, of Massachusetts General Hospital and presented by Katharina M. Eyme. They had recently shown that GBM cancer stem cells are highly susceptible to pharmacological permutation of stearoyl-CoA desaturase (SCD). SCD inhibition in these cells leads to the toxic accumulation of saturated fatty acids and impairs DNA damage repair, hence sensitizing cells to DNA-damaging agents such as temozolomide (TMZ). In this study, YTX-7739, an orally available SCD inhibitor that is in clinical development for the treatment of Parkinson’s disease, was administered either alone or with TMZ to mice following intracranial implantation of GBM cells. The investigators found that YTX-7739, and a second SCD inhibitor in development by Yumanity, YTX-9184, each increased median survival as monotherapy and was synergistic with TMZ in both aggressive and slow growing tumors. The authors concluded that SCD inhibition could possibly be a viable approach to improving treatment of GBM in humans, as either single or adjunctive therapy.

“These data point to modulation of SCD activity as a potential shared therapeutic target between Parkinson’s disease and glioblastoma, expanding the potential promise of our lead asset, YTX-7739, to non-neurodegenerative brain diseases,” said Richard Peters, MD, PhD, President, Chief Executive Officer and Director of Yumanity Therapeutics. “As a science-driven organization that is dedicated to developing disease-modifying drugs for patients with high unmet medical needs, we are working with our collaborators at the Massachusetts General Hospital to explore its compelling preclinical results and how they might be leveraged to benefit patients suffering from glioblastoma.”

YTX-7739 is Yumanity Therapeutics’ proprietary lead small molecule investigational therapy designed to penetrate the blood-brain barrier and inhibit the activity of a novel target, stearoyl-CoA desaturase (SCD). SCD appears to play an important and previously unrecognized role in mitigating neurotoxicity arising from the effects of pathogenic alpha-synuclein protein aggregation and accumulation, which ultimately results in the death of neurons and the subsequent dysregulation of movement and cognition that afflicts patients living with these diseases. Through inhibition of SCD, YTX-7739 modulates an upstream process in the alpha-synuclein pathological cascade and has been shown to rescue or prevent toxicity in cellular and preclinical models. The company is assessing the potential utility of YTX-7739 as a disease modifying therapy for Parkinson’s disease.

SCD is an enzyme that catalyzes fatty acid desaturation, the products of which are incorporated into phospholipids, triglycerides, or cholesterol esters. These lipid-related molecules regulate multiple diverse cellular properties and processes, including membrane structure and function, vesicle trafficking, intracellular signaling and inflammation. SCD expression is regulated by a transcription factor known as SREBF1, which has been identified in human genome-wide association studies as a risk factor for Parkinson’s disease. In preclinical models, SCD inhibition appears to normalize the dynamic interaction of pathological alpha-synuclein with membranes, which improves neuronal function and reduces toxicity, leading to enhanced neuronal survival. Alpha-synuclein-dependent disruption of membrane-related biological pathways, such as vesicle trafficking, is closely linked to the formation of Lewy body protein/membrane aggregations, a hallmark pathological feature of Parkinson’s disease.

Yumanity Therapeutics is a clinical-stage biopharmaceutical company dedicated to accelerating the revolution in the treatment of neurodegenerative diseases through its scientific foundation and drug discovery platform. The company’s most advanced product candidate, YTX-7739, is currently in Phase 1 clinical development for Parkinson’s disease. Yumanity’s drug discovery platform is designed to enable the company to rapidly screen for potential disease-modifying therapies by overcoming toxicity of misfolded proteins in neurogenerative diseases. Yumanity’s pipeline consists of additional programs focused on Lewy body dementia, multi-system atrophy, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), frontotemporal lobar dementia (FTLD), and Alzheimer’s disease. For more information, visit www.yumanity.com.