NUTM1

ZEN-3694 Expands Development to Include Multiple Rare Oncology Indications Calgary, Alberta--(News - February 29, 2024) - Zenith Epigenetics Ltd. ("Zenith" or the "Company") announces its support of Rare Disease Day by highlighting our expanded development efforts of BET inhibitor ZEN-3694 for rare oncology diseases. Rare Disease Day takes place every year on the last day of February, with this leap year day being the rarest of all Rare Disease Days. This event is a global movement to promote equity in healthcare, and access to diagnosis and therapies for individuals living with rare diseases. We are developing ZEN-3694 for the treatment of two aggressive rare cancers with very poor prognosis and no effective approved therapies, NUT carcinoma (NC) and malignant peripheral nerve sheath tumors (MPNST). In addition to clinical trials, we have also provided ZEN-3694 for compassionate use to multiple patients with these diseases and are excited to soon announce results from these important studies. "We are proud to be developing ZEN-3694 to help patients with aggressive, rare forms of cancer, who currently have no access to effective therapies. We are very pleased that NUT carcinoma patients receiving ZEN-3694 in clinical trial and compassionate use settings have benefitted from our drug," said Donald McCaffrey, CEO of Zenith Epigenetics. "Our goal is to improve outcomes and quality of life for NUT carcinoma patients, and we are committed to developing ZEN-3694 through registration for the treatment of this disease. We are also excited about exploring the activity of ZEN-3694 in MPNST, a rare cancer with devastating impact on patients' lives." NC is a highly aggressive type of squamous cell cancer with very poor prognosis that often forms in the head, neck, or lungs. There are currently no effective treatments for this devastating disease that primarily affects adolescents and young adults with a median survival of only 6 months. New diagnostic technologies have allowed for much better diagnosis of NC. The diagnosis rate is increasing rapidly with growing awareness and analytical testing for this disease. ZEN-3694 is being developed in two separate NC clinical trials. The first NC trial, NCT05019716, which combines ZEN-3694 with chemotherapy (etoposide/platinum), is active and recruiting patients. The second trial NCT05372640, combines ZEN-3694 with the CDK4/6 Inhibitor Abemaciclib and is also accruing patients. Both of these trials have shown promising activity. MPNST is a cancer of the cells that form the sheath that covers and protects peripheral nerves. The prevalence of MPNST in the general population is one in 100,000 and comprises 5-10% of all soft-tissue sarcomas. MPNST is most common in young adults, and the prognosis of patients with metastatic disease is extremely poor, with a median survival of less than one year. A clinical trial with ZEN-3694 is in the late planning stage and initiation is expected in the second half of 2024. About NUT Carcinoma and BET inhibition NUT carcinoma is driven by NUTM1 genetic alterations, most commonly fusion to BRD4 (bromodomain-containing protein 4) resulting in a fusion oncoprotein. ZEN-3694 is a BET bromodomain inhibitor that directly binds to NUT fusion proteins, disrupts their activity, and inhibits cancer growth. NUT carcinoma is diagnosed by testing tumor tissue for the fusion protein using immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) or by DNA sequencing to identify the NUT fusion oncogene. About MPNST and BET inhibition MPNST is driven by NF1 gene mutation in 40% of cases. Researchers have identified a BET protein dependency in these NF1-mutant MPNST tumors, and thus ZEN-3694 may disrupt this dependency and inhibit cancer cell growth. About Zenith and ZEN-3694 Zenith Epigenetics Ltd., a wholly owned subsidiary of Zenith Capital Corp., is a clinical stage biotechnology company focused on the discovery and development of novel therapeutics for the treatment of cancer and other disorders with significant unmet medical need. Zenith Epigenetics is developing various novel combinations of BET inhibitors with other targeted agents. Our lead compound, ZEN-3694, is in clinical development for various oncologic indications such as metastatic castration resistant prostate cancer, NUT carcinoma, ovarian cancer and RAS activated tumors. Several of these studies are sponsored by NCI under the NCI-Zenith Cooperative Research & Development Agreements (CRADA) and CRADAs between NCI and other NCI collaborators. For further information, please contact: Investor Relations Phone: 587-390-7865 Email: info@zenithepigenetics.com Website: Forward-Looking Statement This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward looking information relating to the Company's development activities involving ZEN-3694 in NUT carcinoma, malignant peripheral nerve sheath tumor, prostate cancer, ovarian cancer, RAS activated tumors, and other tumor types, as a single agent, or in combination with chemotherapies, including etoposide/platinum, CDK4/6 inhibitors, and other chemotherapy agents, as well as our partnerships, agreements, and collaborations in furtherance of these development activities. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our most recent MD&A which are incorporated herein by reference and are available through SEDAR+ at . The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. Zenith disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. To view the source version of this press release, please visit

Zenith's BET inhibitor ZEN-3694 providing significant clinical benefit in patients with aggressive cancer type Calgary, Alberta--(News - June 1, 2023) - Zenith Epigenetics Ltd. ("Zenith" or the "Company") reports clinical activity and the advancement in development of its BET inhibitor (BETi) ZEN-3694 in patients with NUT carcinoma (NC). NC is a highly aggressive type of squamous cell cancer with very poor prognosis that often forms in the head, neck, or lungs. There are currently no effective treatments for this devastating disease that primarily affects adolescents and young adults with a median survival of only 6 months. NC is considered underdiagnosed with an estimated 1100 cases going undiagnosed in the US every year. The diagnosis rate is increasing rapidly with growing awareness and analytical testing for this disease. Zenith Epigenetics has provided ZEN-3694 to two NC patients for compassionate use and both experienced significant clinical benefit and durable reduction of their tumors. In one case ZEN-3694 was administered as a single agent and in another case in combination with chemotherapy. Concurrently with compassionate use, ZEN-3694 is also being evaluated in two NUT carcinoma clinical trials sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), through the Cancer Therapy Evaluation Program (CTEP) under a Cooperative Research and Development Agreement (CRADA) between Zenith and the NCI. The first trial, NCT05019716, which combines ZEN-3694 with chemotherapy (etoposide/platinum), is active and recruiting patients. The second trial NCT05372640, is in the startup phase and combines ZEN-3694 with the CDK4/6 Inhibitor Abemaciclib. These combinations may increase the response rate and durability above that of either agent alone. "We are very pleased that NUT carcinoma patients receiving ZEN-3694 for compassionate use have benefitted from our drug," said Donald McCaffrey, CEO of Zenith Epigenetics. "We are also very optimistic that the ongoing clinical trials will show clinical benefit and improved quality of life to a patient population with such poor prognosis and no approved therapy options. Besides NUT carcinoma, ZEN-3694 is also currently being evaluated in multiple oncology indications including CRPC, breast cancer, ovarian cancer, colorectal cancer, and lung cancer in 11 clinical trials with various drug combinations. We continue to advance these programs with our partners and are committed to bring this important therapy to these patients." About NUT Carcinoma and BET inhibition NUT carcinoma is driven by NUTM1 genetic alterations, most commonly fusion to BRD4 (bromodomain-containing protein 4) resulting in a fusion oncoprotein. ZEN-3694 is a BET bromodomain inhibitor that directly binds to NUT fusion proteins, disrupts their activity, and inhibits cancer growth. NUT carcinoma is diagnosed by testing tumor tissue for the fusion protein using immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) or by DNA sequencing to identify the NUT fusion oncogene. About Zenith and ZEN-3694 Zenith Epigenetics Ltd., a wholly owned subsidiary of Zenith Capital Corp., is a clinical stage biotechnology company focused on the discovery and development of novel therapeutics for the treatment of cancer and other disorders with significant unmet medical need. Zenith Epigenetics is developing various novel combinations of BET inhibitors with other targeted agents. Our lead compound, ZEN-3694, is in clinical development for various oncologic indications and several studies are sponsored by NCI under the NCI-Zenith CRADA and CRADAs between NCI and other NCI collaborators, specifically: Phase 2b trial in patients with metastatic castration resistant prostate (mCRPC) cancer in combination with androgen receptor inhibitor, XTANDI (enzalutamide), conducted in collaboration with Astellas Pharma and Newsoara Biopharma. Zenith and Newsoara are the trial sponsors (NCT04986423). Phase 2b trial in Triple Negative Breast Cancer (TNBC) patients in combination with the PARP inhibitor (PARPi) TALZENNA (talazoparib), conducted in collaboration with Pfizer and Newsoara Biopharma. Zenith and Newsoara are the trial sponsors (NCT03901469). Phase 1b/2 trial in patients with androgen receptor independent mCRPC in combination with immune checkpoint inhibitor KEYTRUDA (pembrolizumab) and XTANDI (enzalutamide), conducted in collaboration with Merck, the University of California, San Francisco, and the University of Michigan (NCT04471974). Phase 2 trial in combination with TALZENNA (talazoparib) in patients with recurrent ovarian cancer treated with prior PARPi, conducted by the University of Pittsburgh in collaboration with Zenith and Pfizer (NCT05071937). Phase 2 trial in patients with advanced squamous cell lung cancer with NSD3 gene amplification, conducted by Memorial Sloan Kettering Cancer Center (NCT05607108). Phase 1b/2 trial in solid tumors and ovarian cancer patients in combination with immune-checkpoint inhibitors, OPDIVO (nivolumab) and YERVOY (ipilimumab), conducted by the NCI in collaboration with Zenith and BMS (NCT04840589). Phase 1b trial with KEYTRUDA (pembrolizumab) and ABRAXANE (Nab-Paclitaxel) in patients with metastatic TNBC conducted by the NCI in collaboration with Zenith and Merck. (NCT05422794). Phase 2 trial with TALZENNA (talazoparib), in patients with molecularly-selected solid tumors such as PARPi resistant ovarian, prostate cancer, breast, and pancreatic cancers, and solid tumors with RAS pathway alterations conducted by the NCI in collaboration with Zenith and Pfizer (NCT05327010). Phase 1 trial of with the MEK inhibitor MEKTOVI (binimetinib) in solid tumors with RAS pathway alterations and metastatic TNBC conducted by the NCI in collaboration with Zenith and Pfizer (NCT05111561). Phase 1/2 trial with the histone deacetylase inhibitor Entinostat in advanced and refractory solid tumors and lymphomas conducted by the NCI in collaboration with Zenith and Syndax (NCT05053971). Phase 1 trial in combination with Capecitabine in patients with metastatic unresectable colorectal cancer (CRC) conducted by the NCI (NCT05803382). For further information, please contact: Investor Relations & Communications Zenith Epigenetics Phone: 587-390-7865 Email: info@zenithepigenetics.com Website: This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward-looking information relating to the Company's development activities involving ZEN-3694 in NUT carcinoma, prostate cancer, breast cancer, lung cancer, ovarian cancer, pancreatic cancer, lymphomas, colorectal cancer, and other tumor types, as a single agent, or in combination with chemotherapies, including etoposide/platinum, CDK4/6 inhibitors, PARP inhibitors, immune checkpoint inhibitors, androgen receptor inhibitors, MEK inhibitors, histone deacetylase inhibitors, antineoplastics, antimetabolites and other chemotherapy agents, as well as our partnerships, agreements, and collaborations in furtherance of these development activities. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our most recent MD&A which are incorporated herein by reference and are available through SEDAR at . The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. Zenith disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. To view the source version of this press release, please visit

Seven NCI sponsored trials will evaluate safety and efficacy of its BET inhibitor (BETi) ZEN-3694 in combination with several targeted agents and/or chemotherapy in several solid tumor types with significant unmet needCALGARY, Alberta, July 06, 2022 (GLOBE NEWSWIRE) -- Zenith Epigenetics Ltd. (“Zenith” or the “Company”) announced today that its leading BET inhibitor, ZEN-3694, is being evaluated in seven NCI sponsored clinical trials for safety and efficacy in multiple oncology indications with significant unmet need, through the NCI’s Cancer Therapy Evaluation Program (CTEP) under a collaboration between Zenith and NCI, part of the National Institutes of Health. These trials are being conducted by leading investigators and institutions funded by the NCI in the United States and are based on strong pre-clinical rationale for anti-cancer drug combination regimens incorporating ZEN-3694 in advanced and metastatic tumors that are resistant to other therapies. BETis, like ZEN-3694, have been shown in pre-clinical pharmacology studies to sensitize tumors resistant to targeted agents through epigenetic modulation, hence the significant interest in evaluating several such combination therapies. Three of the aforementioned trials are accruing patients, with the remaining five pending activation in the next few months. A rich translational program is embedded in each trial to validate the mechanism of action and identify markers of response and resistance. Combination with immune-checkpoint inhibitors NCT04840589 (enrolling) A Phase I/Ib Trial Evaluating the Safety and Efficacy of BET Inhibitor, ZEN003694 With PD-1 Inhibitor, Nivolumab With or Without CTLA-4 Inhibitor, Ipilimumab in Solid Tumors is evaluating the combination of ZEN-3694 + BMS’s immune-checkpoint inhibitors, Opdivo and Yervoy, in patients with advanced or metastatic solid tumors and wildtype BRCA, platinum resistant ovarian cancer. To date, checkpoint inhibitor trials have had limited success in ovarian cancer, and there are few options after patients progress on targeted therapies. ZEN-3694 has been shown preclinically to address several mechanisms of resistance to checkpoint inhibitors, and may sensitize tumors to the checkpoint combination. The trial is being led by Haider S. Mahdi, MD, Assistant Professor of Obstetrics, Gynecology & Reproductive Sciences at the University of Pittsburgh. NCT05422794 A Phase 1b Trial of ZEN003694 (ZEN-3694) With Pembrolizumab and Nab-Paclitaxel in Patients With Metastatic Triple-Negative Breast Cancer will evaluate the combination of ZEN-3694 + Merck’s immune-checkpoint inhibitor, Keytruda, + Nab-paclitaxel in patients with advanced triple negative breast cancer whose tumors are PD-L1 negative. Keytruda is currently only approved in the PD-L1 positive TNBC population, leaving an unmet need in the PD-L1 negative population. The combination of BET inhibitors and paclitaxel are synergistic preclinically in TNBC. Preclinical rationale exists that combining immunotherapy with BETi and chemotherapy will increase the response rate in patients with PDL1 negative disease. The trial will be led by Ana Garrido-Castro, MD, Medical Oncologist at the Dana-Farber Cancer Institute. Combination with PARP inhibitors NCT05327010 A Phase 2 Trial of the Combination of the BET Inhibitor, ZEN003694 (ZEN-3694), and the PARP Inhibitor Talazoparib, in Patients With Molecularly-Selected Solid Tumors (ComBET) will evaluate the combination of ZEN-3694 plus talazoparib in additional indications such as PARPi resistant ovarian, prostate cancer, breast, and pancreatic cancers, and solid tumors with Ras alterations. This trial builds on the proof of concept shown in Zenith Epigenetics' mTNBC trial (NCT03901469) by expanding into additional indications where PARPi are utilized. BETi including ZEN-3694 has been shown to sensitize germline BRCA wild-type tumors to PARPi, by creating a “BRCAness” phenotype and reverse acquired resistance to PARPi in pre-clinical models. The trial will be led by Timothy A Yap, MBBS PhD FRCP, Associate Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. Combination with MEK inhibitor NCT05111561 (enrolling) A Phase 1 Study of ZEN003694 in Combination With Binimetinib in Solid Tumors With RAS Pathway Alterations and Triple Negative Breast Cancer is evaluating the safety and the activity of ZEN-3694 combined with Pfizer’s MEK inhibitor, Mektovi, in solid tumors with Ras alterations and mTNBC. ZEN-3694 + MEKi have shown synergistic activity in pre-clinical Ras activated tumor models. In Ras activated tumors, acquired resistance to MEKi prevent durable responses. This resistance has been shown to be driven by enhancer modeling and is BET-dependent. Pre-clinical has shown synergy between MEKi and ZEN-3694. The trial is being led by Sarina A. Piha-Paul, MD, Associate Professor at The University of Texas MD Anderson Cancer Center. Combinations with chemotherapy or a CDK4/6 inhibitor for NUT carcinoma NCT05019716 (enrolling) A Phase 1/2 Study of the Bromodomain Inhibitor ZEN003694 in Combination With Etoposide/Platinum in Patients With NUT Carcinoma is evaluating the combination of ZEN-3694 in combination with chemotherapy in the ultra orphan indication NUT carcinoma. NUT carcinoma is a BET-driven, ultra orphan indication with significant unmet need, and with strong pre-clinical and clinical proof of concept. BET inhibitors have been shown to disrupt the major oncogenic driver in NUT carcinoma. The trial is being led by Michael Cheng, MD, Medical Oncologist, at the Dana-Farber Cancer Institute. NCT05372640 A Phase 1 Study of BET Bromodomain Inhibitor ZEN003694 in Combination With the CDK4/6 Inhibitor Abemaciclib in Patients With NUT Carcinoma and Other Solid Tumors will evaluate the combination of ZEN-3694 and Lilly’s CDK4/6 inhibitor, Verzenio, in NUT carcinoma as well. In a NUT carcinoma screen to identify resistance factors to BET inhibition, the CDK4/6 pathway was identified. Preclinically, ZEN-3694 and CDK4/6i are highly synergistic in NUT carcinoma models. The trial will be led by Geoffrey Shapiro, MD, PhD, Medical Oncologist, at the Dana-Farber Cancer Institute. Combination with an HDAC inhibitor NCT05053971 (enrolling) A Phase Ib/II Study of ZEN003694 and Entinostat in Advanced and Refractory Solid Tumors and Lymphomas will evaluate the combination of ZEN-3694 and Syndax’s HDAC inhibitor, entinostat, in solid tumors and lymphoma, with an expansion population in pancreatic cancer. HDACi have been shown pre-clinically in several systems to sensitize cancer cells to BETi, by hyperacetylating histones, the target of BET proteins. The trial will be led by Patricia M. LoRusso, DO, Professor at the Yale School of Medicine. “We are very pleased with our collaboration with the NCI and that ZEN-3694 will be evaluated in additional oncology indications”, said Don McCaffrey, CEO of Zenith Epigenetics. “In addition to expanding the ZEN-3694 PARPi and the ZEN-3694 immune-checkpoint combination to reach additional patients, ZEN-3694’s potential as a combination agent in several different patient populations with a significant unmet need will also be evaluated. The level of interest by leading investigators and the NCI underscore the potential of ZEN-3694 in multiple oncology indications. We continue to advance ZEN-3694 toward registration and are committed to bring an important therapy to cancer patients”. About Zenith and ZEN-3694 Zenith Epigenetics Ltd., a wholly-owned subsidiary of Zenith Capital Corp., is a clinical stage biotechnology company focused on the discovery and development of novel therapeutics for the treatment of cancer and other disorders with significant unmet medical need. Zenith Epigenetics is developing various novel combinations of BET inhibitors with other targeted agents. The lead compound, ZEN-3694, is in clinical development for various oncologic indications in addition to the clinical trials mentioned above, specifically: Phase 2b metastatic castration resistant prostate (mCRPC) cancer trial in combination with androgen receptor inhibitor, XTANDI (enzalutamide), conducted in collaboration with Astellas Pharma Inc and Newsoara Biopharma Co., Ltd. Zenith and Newsoara are the trial sponsors (NCT04986423).Phase 2b Triple Negative Breast Cancer (TNBC) trial in combination with the PARP inhibitor TALZENNA (talazoparib), conducted in collaboration with Pfizer and Newsoara Biopharma Co, Ltd. Zenith and Newsoara are the trial sponsors (NCT03901469).Phase 2 androgen receptor independent mCRPC trial in combination with immune checkpoint inhibitor KEYTRUDA (pembrolizumab) and XTANDI (enzalutamide), conducted by the University of California, San Francisco in collaboration with Merck Sharp & Dohme LLC, the U.S. Army Medical Research and Development Command, and the University of Michigan (NCT04471974). About Triple Negative Breast Cancer (“TNBC”) TNBC is an aggressive form of breast cancer with low survival rates. TNBC accounts for about 10-15% of all breast cancers and it differs from other types of invasive breast cancer in that it tends to grow and spread faster, has fewer treatment options, and tends to have a worse prognosis. The term triple-negative breast cancer refers to the fact that the cancer cells have only low or no amount of the receptors ER, PR, and HER2. Approximately 75,000 women in the US, Japan and the major EU countries are diagnosed with TNBC each year. About Prostate Cancer Prostate cancer is the second-most commonly diagnosed cancer among men and the fifth most common cause of male cancer death worldwide. Adenocarcinoma of the prostate is dependent on androgen for tumor progression and depleting or blocking androgen action has been a mainstay for over six decades. Although tumors are often initially sensitive to medical or surgical therapies that decrease levels of testosterone and to ARSIs that block AR signaling, disease progression ultimately occurs leading to mCRPC. The treatment of prostate cancer patients has evolved rapidly over the past ten years with second generation ARSIs. Despite these advances, many patients with mCRPC fail or develop resistance to existing treatments, leading to continued disease progression and limited survival rates About NUT Carcinoma NUT carcinoma (NC) is a rare, aggressive cancer defined by rearrangements of the NUTM1 gene, most often fusing NUTM1 to a BET protein family member. NC is underdiagnosed, and lacks effective treatments. BET inhibitors have been shown to inhibit NC growth, both preclinically and clinically. About Ovarian Cancer In the US epithelial ovarian cancer is the fifth most common cause of cancer death in women and the most common gynecologic malignancy with about half of women being diagnosed over 65 years of age often with advanced disease. Although primary treatment is effective, most women will relapse and develop resistance to conventional agents. About Ras activated tumors Approximately 40% of colorectal cancer, 30% on non-small cell lung cancer, and 95% of pancreatic cancer carry mutations in the oncogene RAS. Ras-mutant cancers are aggressive and poor prognosis, and Ras small molecule inhibitors only target a small percentage of the total Ras-mutant population. For further information, please contact: Investor Relations & Communications Zenith EpigeneticsPhone: 587-390-7865Email: info@zenithepigenetics.comWebsite: www.zenithepigenetics.com This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward looking information relating to the potential role of ZEN-3694 in the treatment of cancer and other disorders, and the Company’s development of ZEN-3694 including its current and planned clinical studies. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our most recent MD&A which are incorporated herein by reference and are available through SEDAR at www.sedar.com. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. Zenith disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.