Bavituximab

Better 24-month survival was achieved when durvalumab was used for maintenance compared to surveillance in esophagogastric adenocarcinoma patients with “high” Xerna TME Panel immune scores, despite these patients having a poorer prognosis Data suggest the Xerna TME Panel can predict which HER2- esophagogastric adenocarcinoma patients will benefit from checkpoint inhibitors more accurately than PD-L1 combined positive scores WALTHAM, Mass., Sept. 12, 2022 (GLOBE NEWSWIRE) -- OncXerna Therapeutics, Inc. (“OncXerna”), a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates, today announced new biomarker data suggesting the Xerna TME Panel has predictive and prognostic potential in esophagogastric adenocarcinoma. The data are featured in a poster being presented today at the European Society for Medical Oncology (ESMO) Congress 2022. The data featured in the ESMO poster are from retrospective analyses of results from PLATFORM, a randomized Phase 2 trial that evaluated maintenance therapies such as the anti-PD-1 antibody durvalumab in esophagogastric adenocarcinoma patients treated with first-line chemotherapy. Analyses were performed using the Xerna TME Panel, a novel RNA gene expression-based diagnostic panel that uses a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). Using the Xerna TME Panel, researchers analyzed pre-treatment tumor biopsies to classify patients who went on to receive durvalumab maintenance therapy or active surveillance only as immune score “high” or immune score “low.” These classifications were compared against clinical outcomes recorded in the trial. Results showed that immune score high patients had a poorer prognosis with active surveillance compared to immune score low patients. However, despite this poorer prognosis, immune score high patients had improved 6- and 12-month progression free survival and 24-month overall survival with durvalumab maintenance therapy compared to the immune score high patients that received active surveillance. Analyses in the poster also compared the predictive potential of Xerna TME Panel classifications in esophagogastric adenocarcinoma to that of classifications based on PD-L1 combined positive score (CPS) status. “Though specifically tailoring therapeutic regimens for individual patients can be an effective technique in the treatment of GI cancers, its application is limited by a lack of predictive biomarkers,” said Professor Ian Chau, M.D., FRCP, co-author on the poster and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Professor at the Institute of Cancer Research, London & Surrey. “Data being presented at ESMO suggest the Xerna TME Panel can expand the applicability of personalized medicine in esophagogastric adenocarcinoma by predicting the patients who may benefit from anti-PD-1 maintenance therapy more accurately than PD-L1 CPS status. Moreover, classifications incorporating both PD-L1 CPS status and the Xerna TME Panel appear to further distinguish the subset of patients that will derive the most durable clinical benefit from checkpoint inhibitors. Taken together, these encouraging findings support the Xerna TME Panel’s potential as a diagnostic that can help us understand which patients are more likely to benefit from treatment and those that will not. This will hopefully lead to better treatment decisions and improved clinical outcomes for patients.” Key data featured in the ESMO poster are summarized in Tables 1A (patients randomized to active surveillance) and 1B (patients randomized to durvalumab maintenance therapy) below. Table 1A: Survival function estimates for patients enrolled in the active surveillance arm according to Xerna TME Panel and PD-L1 CPS status. Data presented as: rate (97.5% confidence interval)PFS: Progression-free survival; OS: Overall survival Xerna TME Panel Immune Score ClassificationPD-L1 CPS Status High (n=20)Low (n=18)CPS ≥5 (n=19)CPS <5 (n=18)6-month PFS Rate17.5%(3.5% – 40.4%)27.8%(8.3% – 51.8%)18.4%(3.7% – 42.1%)27.8%(8.3% – 51.8%)12-month PFS Rate0%(CI not determined)5.6%(0.2% – 25.7%)0%(CI not determined)5.6%(0.2% – 25.7%)12-month OS Rate46.7%(20.3% – 69.5%)42.1%(16.4% – 66.1%)32.2%(10.1% – 57.1%)59.3%(29.1% – 80.1%)24-month OS Rate8.8%(0.4% – 33.8%)24.1%(6.0% – 48.7%)8.6%(0.3% – 34.6%)23.7%(5.9% – 48.2%) Table 1B: Survival function estimates for patients enrolled in the durvalumab arm according to Xerna TME Panel and PD-L1 CPS status. Data presented as: rate (97.5% confidence interval) Xerna TME Panel Immune Score ClassificationPD-L1 CPS Status High (n=22)Low (n=22)CPS ≥5 (n=26)CPS <5 (n=17)6-month PFS Rate35.0% (13.4% – 57.8%)27.3% (9.4% – 49.0%)28.0% (10.7% – 48.5%)31.3% (9.3% – 56.6%)12-month PFS Rate25.0%(7.5% – 47.7%)4.6% (0.2% – 21.8%)16.0% (4.0% – 35.1%)12.5% (1.4% – 36.1%)12-month OS Rate40.0% (16.7% – 62.6%)40.1% (18.3% – 62.5%)40.0% (18.9% – 60.5%)37.5% (12.9% – 62.6%)24-month OS Rate35.0% (13.4% – 57.8%)22.7% (6.8% – 44.2%)24.0% (8.2% – 44.2%)31.3% (9.3% – 56.6%) Additionally, in PD-L1 CPS ≥5 patients who received durvalumab, 24-month OS rates were 38% and 0% in Xerna TME Panel immune score high (n=17) and low (n=9) subgroups, respectively. Twelve-month OS rates in the same subgroups were 44% and 33%, respectively. Laura Benjamin, Ph.D., Chief Executive Officer of OncXerna Therapeutics and co-author on the ESMO poster, commented, “These results add to an emerging dataset suggesting the Xerna TME Panel can improve the probability of success in clinical trials of not only our internally developed product candidates, navicixizumab and bavituximab, but in trials of a wide range of precision therapies. We are fortunate to be collaborating with leading experts from industry and academia on these efforts, including my co-authors from QIAGEN GmbH, Genialis, and The Royal Marsden. I look forward to continuing our work together as we strive to leverage the XERNA TME Panel to increase the number of cancer patients that can benefit from a precision medicine approach.” A copy of the ESMO poster, entitled: “Predicting benefit from maintenance durvalumab after first-line chemotherapy (1L CTx) in oesophagogastric adenocarcinoma (OGA) using a novel tumour microenvironment (TME) RNA assay,” will be available on the OncXerna website following the conclusion of the ESMO Congress. About PLATFORM PLATFORM was a Phase 2, randomized, multicenter, adaptive study sponsored by The Royal Marsden NHS Foundation Trust that assessed various maintenance therapies in locally advanced or metastatic esophagogastric adenocarcinoma patients. Patients initially received standard chemotherapy according to local practice based upon their HER2 status. HER2-negative patients who completed at least six cycles of standard chemotherapy, achieved stable disease or better on the end-of-treatment CT scan, and met additional eligibility criteria were then randomized to receive active surveillance only or a selected maintenance therapy, one of which was durvalumab. Results showed durvalumab maintenance therapy did not prolong PFS or OS compared to active surveillance in HER2-negative patients unselected for PD-L1 status. For more information on the trial, see Clinicaltrials.gov Identifier: NCT02678182. About the Xerna TME Panel The Xerna TME Panel uses proprietary RNA-based gene expression data and a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). The Xerna TME Panel is an investigational assay that has not been approved and has not been demonstrated to be safe or effective for any use. About OncXerna Therapeutics OncXerna Therapeutics is a clinical stage precision medicine oncology company developing novel therapies to treat solid tumors. Utilizing its innovative precision medicine platform (Xerna™), OncXerna leverages artificial intelligence technologies and RNA expression-based biomarkers to match a specific patient’s tumor with the drugs best suited to treat that tumor. By integrating the Xerna Platform with our deep expertise in clinical development, we believe we can accelerate the development, approval and commercialization of drug product candidates and bring meaningful new treatments to patients as soon as possible. OncXerna’s lead product candidate, navicixizumab, is a bispecific antibody that inhibits both DLL4 and VEGF and is currently being studied in ovarian cancer, triple negative breast cancer, and colorectal cancer. Another product candidate, bavituximab, is an antibody designed to reverse immune suppression by inhibiting phosphatidylserine signaling and is currently in Phase 2 clinical trials. Navicixizumab and bavituximab are investigational agents that have not been approved and have not been demonstrated to be safe or effective for any use. For more information, please visit oncxerna.com, or follow us on LinkedIn and Twitter. Investor and Media Contact: Ashley R. RobinsonLifeSci Partners, LLCarr@lifesciadvisors.com

Multicenter basket trial includes cohorts enrolling patients with colorectal and triple negative breast cancer Trial designed to assess efficacy, safety, and evaluate the relationship between tumor Xerna™ TME Panel biomarker subtype and treatment response WALTHAM, Mass., Sept. 08, 2022 (GLOBE NEWSWIRE) -- OncXerna Therapeutics, Inc. (“OncXerna”), a precision medicine company using an innovative RNA expression-based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates, today announced the initiation of dosing in a Phase 2 basket trial evaluating the anti-DLL4/VEGF bispecific antibody navicixizumab, alone or in combination with chemotherapy, in patients with select advanced solid tumors. The trial is a multicenter, open-label, signal finding study with cohorts in colorectal and triple negative breast cancer currently open for enrollment. The colorectal cancer cohort is evaluating navicixizumab alone and in combination with irinotecan, while the triple negative breast cancer cohort is evaluating navicixizumab alone and in combination with paclitaxel. Per the trial protocol, two additional cohorts designed to enroll patients with ovarian cancer and gastric or gastroesophageal cancer may be opened in the future. In addition to evaluating the safety and efficacy of the studied treatment regimens, the basket trial also seeks to evaluate the potential of the Xerna TME Panel to predict clinical benefit from navicixizumab. The Xerna TME Panel is a novel RNA gene expression-based diagnostic panel developed by OncXerna. Samples will be tested using Exact Sciences’ Oncomap™ ExTra with the Xerna TME Panel to classify patient samples into one of four tumor microenvironment (TME) subtypes based on angiogenic and immune gene expression signatures. The relationship between TME subtypes and the anti-tumor activity of studied regimens will be evaluated as a secondary endpoint in the trial. “Aberrant Notch expression is associated with poor prognosis and treatment resistance in many solid tumors, including colorectal cancer and triple-negative breast cancer. Navicixizumab simultaneously targets inhibition of DLL4, a ligand of the Notch pathway, and VEGF, making this a very attractive therapeutic strategy to evaluate,” said Paul Oberstein, M.D., Director of GI Medical Oncology in the Perlmutter Cancer Center and Associate Professor of Medicine at NYU Langone Health. “We are excited to have this study underway and look forward to evaluating the potential clinical impact of navicixizumab in these settings where patients have limited treatment options and prognosis is poor.” Laura Benjamin, Ph.D., Chief Executive Officer of OncXerna, commented, “This Phase 2 trial is an important milestone for navicixizumab’s development as we seek to build on our promising ovarian cancer data and explore its potential to address unmet needs in other settings where DLL4 plays a key role in treatment resistance. As part of our company’s commitment to expand precision medicine to improve outcomes for patients, we will also evaluate the potential of the Xerna TME Panel to identify patients more likely to respond to treatment with navicixizumab.” About thePhase 2 Trial The Phase 2 basket trial (ONCX-NAV-G201) is a multicenter, open-label, signal finding study designed to enroll up to 180 patients across four cohorts: Colorectal Cancer Cohort: Designed to evaluate navicixizumab alone and in combination with irinotecan in patients with colorectal cancer who have failed two lines of prior standard therapy, including treatment with prior bevacizumab or an equivalent antibody. This cohort will enroll up to 60 patients. Triple Negative Breast Cancer Cohort: Designed to evaluate navicixizumab alone and in combination with paclitaxel in patients with triple negative breast cancer who have received at least two and no more than four prior lines of standard therapy for metastatic disease. Per the trial’s inclusion criteria, prior therapy must include both an immune checkpoint inhibitor in patients with combined positive score > 10, and sacituzumab govitecan. This cohort will enroll up to 60 patients. Gastric/Gastroesophageal Cancer Cohort: Designed to evaluate navicixizumab plus paclitaxel in patients with second-line gastric or gastroesophageal cancer whose prior therapy included an immune checkpoint inhibitor. This cohort will enroll up to 30 patients. Ovarian Cancer Cohort: Designed to evaluate navicixizumab monotherapy in patients with relapsed/refractory ovarian cancer who have received at least two and no more than five prior lines of standard therapy. This cohort will enroll up to 30 patients. The primary endpoints of the trial are objective response rate and progression-free survival. Key secondary endpoints include overall survival, duration of response, safety and tolerability assessments, and the relationship between tumor Xerna TME Panel biomarker subtype and the anti-tumor activity of studied regimens. Xerna TME Panel assessments will be made using formalin-fixed paraffin embedded archive or core tumor samples collected during screening. For more information on the trial, see Clinicaltrials.gov Identifier: NCT05453825. About Navicixizumab Navicixizumab is an anti-DLL4/VEGF bispecific antibody product candidate that demonstrated antitumor activity in patients who were previously treated with Avastin® (bevacizumab) in a Phase 1b clinical trial. The U.S. Food and Drug Administration granted Fast Track designation to navicixizumab for the treatment of high-grade ovarian, primary peritoneal, or fallopian tube cancer in patients who have received at least three prior therapies and/or prior treatment with Avastin®. Navicixizumab is an investigational agent that has not been approved, and it has not been demonstrated to be safe or effective for any use, including for the treatment of advanced ovarian cancer. About the Xerna TME Panel The Xerna TME Panel uses proprietary RNA-based gene expression data and a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). The Xerna TME Panel is an investigational assay that has not been approved and has not been demonstrated to be safe or effective for any use. About OncXerna Therapeutics OncXerna Therapeutics is a clinical stage precision medicine oncology company developing novel therapies to treat solid tumors. Utilizing its innovative precision medicine platform (Xerna™), OncXerna leverages artificial intelligence technologies and RNA expression-based biomarkers to match a specific patient’s tumor with the drugs best suited to treat that tumor. By integrating the Xerna Platform with our deep expertise in clinical development, we believe we can accelerate the development, approval and commercialization of drug product candidates and bring meaningful new treatments to patients as soon as possible. OncXerna’s lead product candidate, navicixizumab, is a bispecific antibody that inhibits both DLL4 and VEGF and is currently being studied in ovarian cancer, triple negative breast cancer, and colorectal cancer. Another product candidate, bavituximab, is an antibody designed to reverse immune suppression by inhibiting phosphatidylserine signaling and is currently in Phase 2 clinical trials. Navicixizumab and bavituximab are investigational agents that have not been approved and have not been demonstrated to be safe or effective for any use. For more information, please visit oncxerna.com, or follow us on LinkedIn and Twitter. Investor and Media Contact: Ashley R. Robinson LifeSci Partners, LLC arr@lifesciadvisors.com