Analysis Uncovered Possible Mechanisms for AZA Resistance that could be Targeted to Induce Response
SAN DIEGO, Calif. December 2, 2018 – Cellworks Group, Inc.,a leader in Precision Medicine and a global pioneer of Therapy Response Index (TRI) technology, today announced that its AI-driven biosimulation technology predicted resistance to Azacitidine (AZA) in newly diagnosed Myelodysplastic Syndromes (MDS) patients with high accuracy. In a cohort of 37 intermediate and high-risk MDS patients, Cellworks predicted AZA non-responders with 100% accuracy.
The results from this study will be featured as a poster presentation (Abstract 3087) at the American Society of Hematology (ASH) Annual Meeting and Exposition held December 1-4, 2018 in San Diego, California. ASH attendees can also get more information by visiting Cellworks booth #201 in the San Diego Convention Center.
“Azacitidine is currently a drug of choice for most of high-risk MDS patients, although only 40-50% experience clinical improvement,” said Shireen Vali, Cellworks Co-founder & CSO. “There is a clear need for a predictive clinical decision support tool to identify MDS patients with a higher or lower likelihood of AZA response. By predicting whether an individual tumor will respond to Azacitidine, we can spare patients life-threatening toxicities and medical expenses for a therapy that has no chance of response, while patients with a high chance for response would receive maximized treatment.”
For this study, Cellworks analyzed the clinical and genomic (NGS, cytogenetics and FISH) data for a cohort of 48 Int-2 and high risk MDS patients who were treated with AZA for median of 12 (4-34) cycles. Patients were treated by AZA until progression to AML.
Cellworks created a Computational Biology Model (CBM) for 37 out of 48 patients utilizing genomic data to create a predictive workflow complemented with digital mechanistic model of AZA and other FDA approved drugs. Drugs were modeled by programming their mechanism of action on pathways and simulated individually and in combination. A disease inhibition score characterized the drug impact on inhibition of the disease phenotypes. For all AZA non-responder profiles, unique combinations were identified that could produce response.
Cellworks CBM accurately predicted the clinical outcomes of 14 out of 20 responders and 17 out of 17 non-responders with overall accuracy 83.78%. Sensitivity of identifying a responder is 70% while non-responders are called with 100% specificity. The CBM identified AZA based combination in 17 patients who did not respond to AZA monotherapy.
In addition, the Cellworks analysis uncovered possible mechanisms for AZA resistance that could be targeted to induce response. Clonal architecture is trackable using ddPCR technology providing time for additional NGS analysis to target the progressing clone.
“This study shows we can improve patient selection for Azacitidine, which can avoid patient risks and side effects of therapies that are not going to produce response and eliminate health care expenses for unsuccessful treatments,” said Yatin Mundkur, CEO of Cellworks. “The high accuracy of Cellworks biosimulation platform could be used to establish criteria for precision enrollment in drug development trials.”
Cellworks is transforming personalized cancer therapy through AI-driven biosimulation software models that represent biomolecular and physiological pathways using the genomic data of each patient. Cellworks personalized medicine predictions help transform lives through the early adoption of successful therapies, while saving time and cost across the healthcare ecosystem. Cellworks also benefits the biopharma industry through virtual clinical trials, improved target identification, lead validation and the ability to repurpose and rescue drugs.
Cellworks Group, Inc. is a world leader in Precision Medicine in the key therapeutic areas of Oncology and Immunology. Cellworks’ unique AI-driven biosimulation platform is a unified representation of biological knowledge, curated from heterogeneous datasets, applied to finding cures. Backed by Sequoia Capital and Artiman Ventures, Cellworks has the world’s strongest trans-disciplinary team of molecular biologists, cellular pathway modelers, and software technologists working towards a common goal – attacking serious diseases to improve the lives of patients. The company is based in San Jose, California and has an R&D facility in Bangalore, India. For more information, visit www.cellworks.life and follow us on Twitter at @cellworkslife.
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Michele Macpherson, Chief Business Officer
Cellworks Group, Inc.