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twoXAR Announces Preclinical Proof-of-Concept Data on Type 2 Diabetes Candidate
By: Business Wire
Jun. 19, 2017 05:37 PM
twoXAR, Inc., an artificial intelligence (AI)-driven biopharmaceutical company, today announced that its candidate, TXR-411, has shown promising results in the db/db mouse model of type 2 diabetes (T2DM). TXR-411 is a molecule that twoXAR identified as having a high probability of being effective in treating T2DM. Proof-of-concept studies in the db/db mouse model were performed by Melior Discovery, a leading research provider of preclinical services that previously achieved positive Phase 2A results with its first-in-class T2DM drug, MLR-1023. The objective of these studies was to further demonstrate proof of concept of twoXAR’s AI platform as a discovery engine capable of uncovering new therapies across a diversified set of diseases.
“The TXR-411 data in the db/db model is impressive given that the initial examination of our candidate achieved an approximately 50 percent decrease in glucose levels, on par with rosiglitazone, without the weight gain associated with rosiglitazone,” said Isaac Hakim, Ph.D, Director of Preclinical Studies at twoXAR. “The reduced glucose and body weight maintenance is exciting in its own right, however, even more compelling is that we selected this disease, identified and shortlisted candidates, and generated efficacious preclinical results in less than three months.”
Nearly four hundred million patients suffer from T2DM globally, and the market size is expected to double by 2025. Given the complex and multifactorial origin of T2DM there remains a high unmet need for novel therapies that work by new mechanisms. Peroxisome Proliferator-Activated Receptor (PPAR) agonists, such as rosiglitazone, were once the leading therapeutic class (commercially) but have since largely been discontinued due to initially unrecognized safety issues. Diabetic therapies which target novel biological pathways may help to reduce the risk of common side effects while improving levels of efficacy. In addition, combination therapies of two and three complementary therapeutics are standard practice and further increase the need for new antidiabetic mechanisms.
Using a clinically translatable model of T2DM (db/db mice), the data showed that TXR-411 significantly reduced blood glucose levels and improved the results of oral glucose tolerance as effectively as rosiglitazone. These results were achieved without any of the weight gain that is associated with PPAR agonists like rosiglitazone. Seeing potentially promising results in the db/db model is meaningful as this model incorporates many aspects of human T2DM including hyperglycemia, obesity, and impaired beta-cell function.
“Over the last 12 months we have publicly announced positive preclinical proof-of-concept data in rheumatoid arthritis, liver cancer, and now type 2 diabetes,” said Andrew A. Radin, co-founder and CEO of twoXAR. “Across these studies we have seen that about 30 percent of the novel candidates we test in preclinical studies show statistically significant efficacy signals in the in vivo models’ respective endpoints.”
twoXAR computationally screened a library of more than 25,000 potential drug candidates. The three with the strongest evidence for potential efficacy and safety were selected for these studies. Each candidate was identified using twoXAR’s computational drug discovery platform which utilizes artificial intelligence to rapidly perform unbiased analyses of biological, chemical, and clinical data to predict and rank potentially efficacious drugs. This strategy offers a new route to unique intellectual property rights that allow for the rapid development of a drug while maximizing the opportunity to identify the most efficacious molecule.
Preclinical studies were conducted by researchers at Melior Discovery, under the direction of John Ciallella, Ph.D, Director of Research at Melior Discovery and Melior Pharmaceuticals.
twoXAR is an artificial intelligence-driven biopharmaceutical company. The company leverages its computational platform to identify promising drug candidates, de-risks the opportunities through preclinical studies, and progresses drug candidates to the clinic through industry partnerships. Based in Palo Alto, California, the twoXAR team includes experts in drug discovery and development, biomedical informatics, computational biology, data science and software development. For more information please visit, www.twoXAR.com.
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