Yumanity Therapeutics’ YTX-7739 Demonstrates Prevention of Motor Function Deficits in a Parkinson’s Disease Mouse Model
Yumanity Therapeutics (NASDAQ: YMTX) announced promising pre-clinical results for YTX-7739, its lead therapy for Parkinson's disease, at the AD/PD™ 2021 conference. The study presented evidence of the drug's pharmacological and physiological efficacy in a mouse model, demonstrating significant prevention of motor function deficits and improved survival of dopaminergic neurons. YTX-7739 inhibits stearoyl-CoA desaturase (SCD), reducing toxic α-synuclein levels. This study supports ongoing clinical development of YTX-7739 as a potential disease-modifying therapy for Parkinson's disease.
- YTX-7739 shows significant efficacy in preventing motor function deficits in PD mouse models after four months of oral dosing.
- The drug demonstrated improved biochemical measures of α-synuclein pathology compared to controls.
- YTX-7739 enhances the survival of dopaminergic neurons, crucial for Parkinson's disease treatment.
- None.
YTX-7739 demonstrates pharmacological, physiological, and behavioral pre-clinical proof of concept in in vivo model
Study presented at AD/PD™ 2021
BOSTON, March 09, 2021 (GLOBE NEWSWIRE) -- Yumanity Therapeutics (NASDAQ: YMTX), a clinical-stage biopharmaceutical company focused on the discovery and development of innovative, disease-modifying therapies for neurodegenerative diseases, today announced results of a study of its lead program, YTX-7739, that demonstrate pharmacological, physiological and behavioral pre-clinical proof of concept in a Parkinson’s disease (PD) mouse model. This oral presentation and two posters will be presented at the 15th Annual International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD™ 2021) Virtual Conference, March 9 to 14, 2021.
“Evidence suggests that α-synuclein pathology is a strong risk factor for Parkinson’s disease,” said Dan Tardiff, Ph.D., interim Head of Research and Scientific Co-founder at Yumanity Therapeutics. “Our proprietary discovery platform led us to the target stearoyl-CoA desaturase (SCD), which when inhibited decreases the toxicity associated with pathogenic α-synuclein. Inhibition of SCD, an enzyme involved in lipid metabolism, has been shown to prevent α-synuclein pathology in multiple models, including patient-derived neurons, in vitro. The results from the current study demonstrate that YTX-7739 has a similar effect in a mouse model of Parkinson’s disease-related pathology. These results lend additional evidence to support our ongoing clinical program in Parkinson’s disease patients.”
The research entitled, YTX-7739, A Clinical Stage Stearoyl-CoA Desaturase Inhibitor for Parkinson’s Disease Improves Behavioral and Pathological Features in an a-Synuclein Mouse Model, conducted in collaboration with the laboratories of Silke Nuber, Ph.D., and Dennis Selkoe, M.D., at Brigham & Women’s Hospital, will be presented at 12:30 p.m. [CET] on March 13 (live discussion March 13 from 5:30 to 6 p.m. CET) by Dr. Tardiff. The study evaluated YTX-7739 vs. control in the PD mouse model. The model was used to evaluate the effect of the drug on motor function as well as survival of neurons and associated biochemical features. The effects of the drug on lipid metabolism were also examined. The investigators found:
- YTX-7739 prevented motor function deficits in the diseased mice after four months of YTX-7739 oral dosing compared to placebo-treated mice.
- YTX-7739 concentrations in the brain reached a level that engaged and inhibited SCD activity consistent with in vitro studies. In addition, SCD inhibition by YTX-7739, which can be measured by a quantitative biomarker, resulted in a decrease in monounsaturated fatty acids in both plasma and brain. Monounsaturated fatty acids may contribute to α-synuclein pathology.
- Multiple biochemical measures of α-synuclein pathology were significantly improved in mice with YTX-7739 as compared to controls, including levels of pathological α-synuclein. The reduction in levels of pathological α-synuclein was also confirmed via histopathological analysis.
- Mice treated with YTX-7739 exhibited enhanced survival of dopaminergic neurons, the type of neuron that selectively dies in the brains of patients with Parkinson’s disease.
The results indicate that YTX-7739 actively engages with its intended target, SCD, in the mouse brain. The observed improvements in pathology and neuron survival, and the resultant correction of motor dysfunction in mice provided added evidence for SCD inhibition as a potential treatment approach for Parkinson’s disease, and further support for the on-going evaluation of YTX-7739 in humans.
Posters to be presented at AD/PD 2021
Non-Clinical Pharmacokinetic and Pharmacodynamic Properties of YTX-7739, a Clinical Stage Stearoyl-CoA Desaturase Inhibitor for Parkinson’s Disease
Poster #: P499 / #1463
Topic: Theme C: α-Synucleinopathies / C2.a. Therapeutic Targets, Mechanisms for Treatment: Αlpha-synuclein
Authors: D. Tardiff, M. Lucas, I. Wrona, B. Chang, C. Chung, B. Le Bourdonnec, K. Rhodes, R. Scannevin
Summary: YTX-7739 is an inhibitor of SCD, an enzyme that desaturates fatty acids. The objective of the study was to characterize the pharmacokinetic properties of YTX-7739 in rats and cynomolgus macaques and the corresponding pharmacodynamic changes in fatty acid profiles. YTX-7739 was found to be well-tolerated and brain penetrant in both species. It was a potent inhibitor of SCD in vivo where it reduced the levels of unsaturated fatty acids in a dose dependent manner.
A Three-Dimensional Patient-Derived Cortical Neurosphere Model of Parkinson’s Disease
Poster #: P497 / #942
Topic: Theme C: α-Synucleinopathies / C2.a. Therapeutic Targets, Mechanisms for Treatment: Αlpha-synuclein
Authors: W. Raja, E. Neves, C. Burke, X. Jiang, P. Xu, V. Khurana, C. Chung, R. Scannevin
Summary: The objective of the study was to develop a patient-derived induced pluripotent stem cell PD model. Three-dimensional neurospheres were created and exhibited relevant PD phenotypes that responded to SCD inhibitors. These neurospheres have been used by Yumanity to evaluate the potential of small molecule therapeutics.
About YTX-7739
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), that plays an important and previously unrecognized role in modulating neurotoxicity arising from the alpha-synuclein protein, a major driver of Parkinson’s disease and related neurodegenerative disorders. Misfolding and aggregation of alpha-synuclein triggers a cascade of events, ultimately resulting in neurotoxicity and the subsequent impairment of movement and cognition that afflicts patients living with this disease. 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 preclinical models. The company is assessing the potential utility of YTX-7739 in Parkinson’s disease.
About SCD
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.
About Yumanity Therapeutics
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, please visit www.yumanity.com.
Forward-Looking Statements
This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “aims,” “anticipates,” “believes,” “could,” “designed to,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding the potential therapeutic benefits of our prospective product candidates and results of preclinical studies, including YTX-7739, and the design, commencement, enrollment, and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, and the anticipated benefits of our drug discovery platform. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.
Any forward-looking statements in this press release are based on Yumanity Therapeutics’ current expectations, estimates and projections about our industry as well as management’s current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of our product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of Yumanity Therapeutics or our collaborators, the risk that Yumanity Therapeutics may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that Yumanity Therapeutics may not realize the intended benefits of its drug discovery platform, the risk that our product candidates will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving Yumanity Therapeutics’ product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Yumanity Therapeutics’ actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled “Risk Factors” in the definitive proxy statement/prospectus/information statement filed with the Securities and Exchange Commission on November 12, 2020, as well as discussions of potential risks, uncertainties, and other important factors in Yumanity Therapeutics’ subsequent filings with the Securities and Exchange Commission. Yumanity Therapeutics explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
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