TAK-243

SEATTLE, April 17, 2023 /PRNewswire/ -- Presage Biosciences, a pioneer in translational oncology whose mission is understanding the complexity of drug response in the tumor microenvironment (TME), will present at the Immunology, TME Minisymposium at the American Association for Cancer Research (AACR) 2023 Annual Meeting. In an independent study, Presage's innovative multiplexed trackable microdosing platform (CIVO®) was used to introduce an investigational ubiquitin inhibitor (TAK-243) alone and in combination with anti-PD1. The resulting data demonstrated that TAK-243 has potential to increase anti-tumor immunogenicity and prime tumors for response to immune checkpoint inhibition. The Session (MS.IM01.03 – Immune Checkpoints at Tumor Beds, #3476) is titled "TAK-243 increases tumor immunogenicity enhancing systemic anti-tumor immune response and tumor regression in combination with immune checkpoint inhibition in a syngeneic model of lymphoma" and will be presented live on April 17, 2023 from 3:52pm-4:07pm EST. "We are excited to showcase these novel findings on the TME and how we have paired CIVO with sophisticated spatial profiling to translate preclinical findings to human disease" said Richard Klinghoffer, Presage's Chief Executive Officer. "We continue our work with fellow innovators in oncology to deliver key translational data early in the clinical development process." After AACR 2023, Presage Biosciences' CIVO technology will be further showcased at two events: The 4th Annual International Phase-0/Microdosing Stakeholder Meeting in Boston, MA on April 24th. Presage is featured speaker, panel moderator and sponsor at this year's event; Life Science Innovation Northwest (LSINW) in Seattle, WA on April 25. LSINW is the Pacific Northwest's largest annual life science conference. About CIVO Comparative In Vivo Oncology (CIVO) is Presage's patented platform that enables multiplexed intratumoral microdosing and generation of deep spatial biology insights. Presage's CIVO technology and analysis capabilities are unparalleled at providing insight into drug-exposed areas of the intact tumor microenvironment. Presage is pairing the use of CIVO with molecular profiling technologies in both preclinical and Phase 0 trials in order to inform and de-risk oncology drug development. About Presage Presage Biosciences is a translational oncology company dedicated to understanding the complexity of drug response in the tumor microenvironment. Presage partners with oncology-focused pharmaceutical companies through strategic alliances along with other innovators who are at the forefront of spatial biology and oncology drug development. Presage is privately held and based in Seattle. For more information, visit . Media Contact: Julie Rathbun Rathbun Communications (206) 769-9219 [email protected] SOURCE Presage Biosciences

Researchers have set their sights on a new therapeutic target for an aggressive form of breast cancer with limited treatment options. Through a comprehensive and cutting-edge genomic screening method known as CRISPR/CAS9 screening, scientists were able to identify a specific enzyme called UBA1 that revealed itself as an ideal therapeutic target. Using a novel UBA-inhibiting drug called TAK-243, they blocked the cellular function of UBA1 and effectively killed cancer cells in patient-derived breast tumors in mice. Researchers at VCU Massey Cancer Center have set their sights on a new therapeutic target for an aggressive form of breast cancer with limited treatment options. Breast cancer is the second most common cancer in U.S. women, and triple-negative breast cancer (TNBC) is a more aggressive and deadly form of disease that accounts for 10-15% of all breast tumors. TNBC grows and spreads more quickly than other breast tumors and is associated with worse patient outcomes, accounting for nearly one-third of all breast cancer-related deaths. Additionally, TNBC affects Black women disproportionately: Black women die from TNBC at a significantly higher rate than white women despite being diagnosed at a younger age. Finding an effective therapy that works well in all patients would be an important step in addressing this disparity. Through a comprehensive and cutting-edge genomic screening method known as CRISPR/CAS9 screening, Massey scientists -- led by Anthony Faber, Ph.D., and Jennifer Koblinski, Ph.D. -- were able to identify a specific enzyme called UBA1 that revealed itself as an ideal therapeutic target. Using a novel UBA-inhibiting drug called TAK-243, they blocked the cellular function of UBA1 and effectively killed cancer cells in patient-derived breast tumors in mice. Previous research has shown that UBA1 inhibitors can have a positive impact in hematological cancers such as acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML). This study -- recently published in PNAS Nexus -- is the first to suggest that UBA1 inhibitors could be effective in TNBC. TAK-243 has been tested recently in early phase trials, paving the way for potential testing in TNBC patients. "We found that the majority of TNBC cells in our study were uniformly susceptible to the antitumor effects of TAK-243," said Koblinski, director of the Cancer Mouse Models Core and member of the Cancer Biology research program at Massey, as well as an associate professor of pathology at the VCU School of Medicine. "In addition to demonstrating this drug's success at the local site of the primary breast cancer, our findings demonstrate that TAK-243 can also shrink tumors in various organs after the disease has spread." The researchers also determined that the c-MYC gene -- an important and infamously difficult drug target in TNBC -- can be harnessed to cooperate with TAK-243 to initiate a cellular stress response and enhance the drug's ability to fight TNBC. This supports the notion that TAK-243 may be effective in high-cMYC-expressing TNBC, where c-MYC may serve as a biomarker for response to the drug. Chemotherapy remains one of the few routinely utilized treatment options for TNBC, with variable patient responses and little efficacy. "The implementation of targeted therapies -- drugs that target a specific genetic defect -- has been revolutionary in treating different cancers, including breast cancer," said Faber, co-leader of the Developmental Therapeutics research program and Natalie N. and John R. Congdon, Sr. Endowed Chair in Cancer Research at Massey, as well as an associate professor in the Philips Institute for Oral Health Research at the VCU School of Dentistry. However, the hormone receptors, estrogen receptors or human epidermal growth factor receptor 2 (HER2) that can be effectively targeted in breast cancer treatment are missing in TNBC, hence the name "triple-negative breast cancer." "Genomic and clinical evidence suggests that the implementation of targeted therapies in the treatment of TNBC will require an expansion of potential targets," Faber said. "Our study may have identified a key and novel target for the development of new therapies." Faber added, "Importantly, as TNBC is a major disease of disparate outcomes between Black patients and white patients, we were able to harness the power of new breast cancer mouse models from Black TNBC patients that were developed by Dr. Koblinski's group. Traditionally, these models have been underrepresented and are important new tools to identify effective therapies for Black patients. The most exciting part of the study was that we found TAK-243 was effective across these models, suggesting TAK-243 or other UBA1 inhibitors could be equally effective in all TNBC patients." The next steps of this research include exploring the use of TAK-243 in TNBC with the drug company that is developing it, and evaluating other targets in the UBA1 pathway that may also demonstrate efficacy.