Unresectable Colorectal Carcinoma

Calgary, Alberta--(News - October 25, 2023) - Zenith Epigenetics Ltd. ("Zenith" or the "Company"), a global leader in epigenetics, announced today it has entered into an agreement with Cencora (formerly AmerisourceBergen) aimed at accelerating the commercialization of Zenith Epigenetics' ZEN-3694 program. The ZEN-3694 program is an advanced epigenetic approach to synergistically advancing the efficacy of cancer treatment of currently marketed drugs. Existing partners and collaborators include Pfizer, Merck, BMS, Eli Lilly, Astellas, GSK, and Syndax and is supported by numerous collaborators and partners such as National Cancer Institute, National Institute of Health, Dana Farber - Harvard, Yale, UCSF, Memorial Sloan Kettering, and MD Anderson. As part of the agreement, Cencora will provide a variety of services to strategize ZEN-3694's market introduction. The initial focus will be in evaluating regulatory and market access to provide insights into potential barriers and opportunities for ZEN-3694's introduction. The insights will be used to tailor ZEN-3694's development and to design successful patient access and adherence programs that add value for the entire healthcare system. "We're excited to work with Cencora and their team on the future of ZEN-3694," said Donald J. McCaffrey, Zenith's Chairman, Founder, and CEO. "They share our vision and passion for impacting patients in a positive and meaningful way, with a strong eye for what tomorrow will bring. We know that ZEN-3694 will innovate the future of oncology and are proud to work with Cencora on the next steps of bringing ZEN-3694 into the lives and homes of patients nationwide and, in time, globally." "For a product with the immense capabilities ZEN-3694 has, we knew we needed a partner with immeasurable experience across healthcare, unmatched distribution capabilities, and a global impact," said Donald J. McCaffrey. "Cencora emerged as the best partner to lead the commercial and distribution strategy for ZEN-3694 with innovation, strategic thinking, and careful planning around patient access and the patient experience." "As biotech and pharmaceutical companies invest in the development of new products, we remain focused on delivering integrated support across the clinical and commercialization journey to help them bring their innovations to market," said Sandra Anderson, senior vice president of International Commercialization at Cencora. "We are thrilled to support Zenith's pre-commercial launch preparations and will provide the solutions they need to help them accelerate time-to-market and maximize commercial success." While Zenith continues its work on ZEN-3694's technology platform, Cencora's teams will identify key avenues and opportunities for ZEN-3694's commercialization and market entry. 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: Randomized 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 1b/2 trial in patients with androgen receptor independent mCRPC in combination with immune checkpoint inhibitor KEYTRUDA (pembrolizumab) and XTANDI (enzalutamide), conducted by the University of California, San Francisco in collaboration with Merck and Zenith (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 1b/2 trial in platinum resistant 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 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 with chemotherapy (Etoposide and Cisplatin) in patients with metastatic or unresectable NUT carcinoma conducted by the NCI in collaboration with Zenith (NCT05019716). Phase 1 trial with abemaciclib (Verzenio) in patients with metastatic or unresectable NUT carcinoma and other solid tumors conducted by the NCI in collaboration with Eli Lilly and Zenith (NCT05372640). 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 of with the MEK inhibitor binimetinib (MEKTOVI) in solid tumors with RAS pathway alterations and metastatic TNBC conducted by the NCI in collaboration with Zenith and Pfizer (NCT05111561). 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 in patients with advanced squamous cell lung cancer with NSD3 gene amplification, conducted by Memorial Sloan Kettering Cancer Center in collaboration with Zenith (NCT05607108). Phase 1 trial in combination with Capecitabine in patients with metastatic unresectable colorectal cancer (CRC) conducted by the NCI in collaboration with Zenith (NCT05803382). Phase 1b trial in combination with M1774 (ATR inhibitor) for the treatment of ARID1A mutant recurrent ovarian and endometrial cancer conducted by the NCI in collaboration with Merck KGgA and Zenith (NCT05950464). About Cencora Cencora is a leading global pharmaceutical solutions organization centered on improving the lives of people and animals around the world. We partner with pharmaceutical innovators across the value chain to facilitate and optimize market access to therapies. Care providers depend on us for the secure, reliable delivery of pharmaceuticals, healthcare products, and solutions. Our 46,000+ worldwide team members contribute to positive health outcomes through the power of our purpose: We are united in our responsibility to create healthier futures. Cencora is ranked #11 on the Fortune 500 and #24 on the Global Fortune 500 with more than $200 billion in annual revenue. Learn more at . 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 collaboration with Cencora and the Company's development activities involving ZEN-3694 for the treatment of various oncologic indications and other disorders, 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

Designations for Daiichi Sankyo and AstraZeneca's ENHERTU include patients with HER2 expressing metastatic solid tumors and HER2 positive metastatic colorectal cancer ENHERTU has now been granted seven Breakthrough Therapy Designations TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)-- ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been granted two additional Breakthrough Therapy Designations (BTDs) in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, and for the treatment of patients with HER2 positive (IHC 3+) metastatic colorectal cancer who have received two or more prior regimens. ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN). HER2 overexpression has been observed in 1% to 28% across various types of metastatic solid tumors and in up to 5% of patients with colorectal cancer.1,2,3,4 There is an unmet need for effective therapies for these tumor types, particularly for patients who have progressed on or are refractory to standard of care therapies.5,6 The U.S. Food and Drug Administration (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The new medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines. The FDA granted the BTD for the treatment of metastatic HER2 positive solid tumors based on results from the ongoing DESTINY-PanTumor02 phase 2 trial with supporting data from other trials in the ENHERTU clinical development program. Results from an interim analysis of DESTINY-PanTumor02 were presented as a late-breaking oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in previously treated patients with HER2 expressing metastatic solid tumors including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic cancers and other tumors. The BTD for the treatment of HER2 positive metastatic colorectal cancer was based on final results from the DESTINY-CRC01 phase 2 trial presented at the 2022 ASCO Gastrointestinal Cancers Symposium (ASCO GI) and primary results from the DESTINY-CRC02 phase 2 trial presented at the 2023 ASCO Annual Meeting. “ENHERTU is the first HER2 directed therapy to demonstrate a potential benefit across a series of difficult-to-treat cancers and these designations are recognition of the continued potential of this innovative medicine,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We remain committed to exploring additional opportunities for ENHERTU in these tumor types with the goal of bringing this treatment to more patients as soon as possible.” “This is an important step in bringing ENHERTU to patients with a broad range of HER2 expressing solid tumors who currently face a poor prognosis,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “We are encouraged by the recently reported results from our pan-tumor and colorectal cancer trials that contributed to these designations, and we look forward to working closely with the FDA to provide these patients with a potential new targeted treatment option.” ENHERTU has received seven BTDs and its designation in HER2 expressing metastatic solid tumors represents the first time ENHERTU has been granted this designation in a tumor agnostic setting. ENHERTU previously received BTDs for three indications in breast cancer, including HER2 low metastatic breast cancer, second-line HER2 positive metastatic breast cancer and later-line HER2 positive metastatic breast cancer. Two additional BTDs for ENHERTU were granted for HER2 (ERBB2) mutant metastatic non-small cell lung cancer (NSCLC) and HER2 positive metastatic gastric cancer. About DESTINY-PanTumor02 DESTINY-PanTumor02 is a global, multicenter, multi-cohort, open-label phase 2 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) for the treatment of HER2 expressing tumors (IHC 3+ or IHC 2+), including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer and other tumors. The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed objective response rate (ORR) as assessed by investigator. Secondary endpoints include duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety, tolerability and pharmacokinetics. DESTINY-PanTumor02 has enrolled 268 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov. About DESTINY-CRC01 DESTINY-CRC01 is a global, phase 2, open-label, multicenter trial evaluating the efficacy and safety of ENHERTU (6.4 mg/kg) in patients with HER2 expressing unresectable and/or metastatic colorectal cancer. The primary endpoint of the main cohort of DESTINY-CRC01, which enrolled 53 patients with HER2 positive (IHC 3+ or IHC 2+/in-situ hybridization [ISH]+) metastatic colorectal cancer, was confirmed ORR as assessed by independent central review. Secondary endpoints include DCR, DoR, PFS, OS and safety. Two additional exploratory cohorts enrolled patients whose tumors had lower levels of HER2 expression (HER2 IHC 2+/ISH- [n=15], and HER2 IHC 1+ [n=18], respectively). DESTINY-CRC01 enrolled 86 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov. About DESTINY-CRC02 DESTINY-CRC02 is a global, randomized, two arm, parallel, multicenter phase 2 trial evaluating the efficacy and safety of two doses (5.4 mg/kg or 6.4 mg/kg) of ENHERTU in patients with locally advanced, unresectable or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) colorectal cancer of BRAF wild-type, or RAS wild-type and RAS mutant tumor types previously treated with standard therapy. The trial was conducted in two stages. In the first stage, patients (n=80) were randomized 1:1 to receive either 5.4 mg/kg or 6.4 mg/kg of ENHERTU. In the second stage, additional patients (n=42) were enrolled in the 5.4 mg/kg arm. The primary endpoint is confirmed ORR as assessed by blinded independent central review. Secondary endpoints include DoR, DCR, investigator-assessed confirmed ORR, clinical benefit ratio, PFS, OS and safety. DESTINY-CRC02 enrolled 122 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov. About HER2 Expression in Solid Tumors HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.5,7 In some cancers, HER2 expression is amplified or the cells have activating mutations.7,8 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.9 While HER2 directed therapies have been used to treat breast, gastric, lung and colorectal cancers, more research is needed evaluating their potential role in treating other HER2 expressing tumor types.3,5,10 HER2 is an emerging biomarker in biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.8 Testing is not routinely performed in these additional tumor types and as a result, available literature is limited. HER2 overexpression has been observed at rates from 1% to 28% in these solid tumors.1,2 There is an unmet need for effective therapies for certain HER2 expressing solid tumors, particularly for those who have progressed on or are refractory to standard of care therapies as there are currently no approved HER2 directed therapies for biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.5,6 Colorectal cancer is the third most common and second most common cause of cancer deaths worldwide with more than 1.9 million patients diagnosed and more than 935,000 deaths globally in 2020.11 Approximately 25% of patients have metastatic disease at diagnosis, meaning the disease has spread to distant organs and about 50% of patients with colorectal cancer will eventually develop metastases.12 For patients with metastatic disease, up to 5% are HER2 overexpressing.3,4 About ENHERTU ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker. ENHERTU (5.4 mg/kg) is approved in more than 50 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU (5.4 mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. ENHERTU (5.4 mg/kg) is approved in Israel, Japan and under accelerated approval in the U.S. for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trials. About the ENHERTU Clinical Development Program A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan. About the DXd ADC Portfolio of Daiichi Sankyo The DXd ADC portfolio of Daiichi Sankyo currently consists of five ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Three additional Daiichi Sankyo DXd ADCs include patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd; DS-7300), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd; DS-6000), a CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan and raludotatug deruxtecan are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. ENHERTU U.S. Important Safety Information Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either: – In the metastatic setting, or – In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception. Contraindications None. Warnings and Precautions Interstitial Lung Disease / Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg) In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. Median time to first onset was 5 months (range: 0.9 to 23). Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21). Neutropenia Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level. Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg) In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Sixteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 664). Febrile neutropenia was reported in 1.1% of patients. Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients. Left Ventricular Dysfunction Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment. Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg) In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.6% of patients, of which 0.4% were Grade 3. Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Embryo-Fetal Toxicity ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU. Additional Dose Modifications Thrombocytopenia For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level. Adverse Reactions Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg) The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 984 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, and DESTINY-Lung02. Among these patients 65% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (71%), decreased hemoglobin (66%), decreased neutrophil count (65%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (47%), increased aspartate aminotransferase (48%), vomiting (44%), increased alanine aminotransferase (42%), alopecia (39%), increased blood alkaline phosphatase (39%), constipation (34%), musculoskeletal pain (32%), decreased appetite (32%), hypokalemia (28%), diarrhea (28%), and respiratory infection (24%). HER2-Positive Metastatic Breast Cancer DESTINY-Breast03 The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg intravenously every three weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30). Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (one patient each). ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), hypokalemia (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), respiratory infection (22%), headache (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%). HER2-Low Metastatic Breast Cancer DESTINY-Breast04 The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU. Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each). ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and hypokalemia (25%). Unresectable or Metastatic HER2-Mutant NSCLC (5.4 mg/kg) DESTINY-Lung02 evaluated two dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis. The safety of ENHERTU was evaluated in 101 patients with unresectable or metastatic HER2-mutant NSCLC who received ENHERTU 5.4 mg/kg intravenously every three weeks in DESTINY‑Lung02. Nineteen percent of patients were exposed for >6 months. Serious adverse reactions occurred in 30% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I. Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%). ENHERTU was permanently discontinued in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, diarrhea, hypokalemia, hypomagnesemia, myocarditis, and vomiting. Dose interruptions of ENHERTU due to adverse reactions occurred in 23% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), increased alkaline phosphatase (22%), and alopecia (21%). Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU. Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%). ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%). Use in Specific Populations Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU. Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose. Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility. Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients. Geriatric Use: Of the 883 patients with breast cancer treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.6% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (60%) as compared to younger patients (48%). Of the 101 patients with unresectable or metastatic HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min). Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST). To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch. Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit . ________________________________ References 1 Yan M, et al. Cancer Metastasis Rev. 2015;34(1):157–164. 2 Buza N, et al. Modern Pathology. 2013 Dec;26(12):1605-12. 3 Siena S, et al. Ann Oncol. 2018 May; 29(5):1108–1119. 4 Ross JS, et al. Cancer. 2018;124:1358-1373. 5 Iqbal N, et al. Mol Biol Int. 2014;852748. 6 Meric-Bernstam F, et al. J Clin Oncol. 2021; 39:15: 3004-3004. 7 ASCO. Breast Cancer. Accessed August 2023. 8 Omar N, et al. Pathogenesis. 2015;2(3):1-9. 9 Pillai R, et al. Cancer. 2017;1;123(21): 4099-4105. 10 National Cancer Institute. Enhertu Marks First Targeted Therapy for HER2-Mutant Lung Cancer. Accessed August 2023. 11 GLOBOCAN 2020. Colorectal Cancer. Accessed August 2023. 12 Van Cutsem E, et al. Ann Oncol. 2014;25(suppl 3): iii 1-9.

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