A Phase II Study of Sequential Bipolar Androgen Therapy and ZEN-3694 in Sequence With Enzalutamide + ZEN-3694 in Asymptomatic Patients With Metastatic CRPC: The COSMYC Trial (COmbined Suppression of MYC)

This research is being done to determine if receiving the combination of testosterone and ZEN-3694 followed by the combination of enzalutamide plus ZEN-3694 will decrease the size of tumors in patients with prostate cancer that has become resistant to castration and other therapies. The investigators also want to determine if dosing first with the combination of testosterone and ZEN-3694 may cause enzalutamide and ZEN-3694 to work more effectively.

Start Date30 Jun 2025

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

[+2]

NCT06102902

/ RecruitingPhase 1IIT

A Phase 1 Study of ZEN003694 (ZEN-3694) in Combination With Cetuximab and Encorafenib in Patients With Refractory BRAF V600E Metastatic Colorectal Cancer

This phase I trial tests the safety, best dose, and effectiveness of ZEN003694 in combination with cetuximab and encorafenib in treating patients with colorectal cancer that has not responded to previous treatment (refractory), that has come back after a period of improvement (relapsed), and that has spread from where it first started (primary site) to other places in the body (metastatic). ZEN003694 is a protein inhibitor that binds to BET proteins. When ZEN003694 binds to BET proteins, it disrupts gene expression. Preventing the expression of certain growth-promoting genes may inhibit proliferation of tumor cells that over-express BET proteins. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Encorafenib is an enzyme inhibitor. It inhibits pathways that are responsible for controlling cell proliferation and survival, which may lead to a decrease in tumor cell proliferation. Both cetuximab and encorafenib have been approved to treat cancer. Adding ZEN003694 to cetuximab and encorafenib may be more effective at treating patients with refractory metastatic colorectal cancer than giving the usual treatment (cetuximab and encorafenib) alone.

Start Date05 Jun 2024

Sponsor / Collaborator

National Cancer Institute

NCT06161493

/ WithdrawnPhase 1IIT

Phase l Study of a BET Inhibitor, ZEN003694, Combined With a PARP Inhibitor, Niraparib in Patients With Metastatic or Recurrent Solid Tumors

This Phase I, open label, dose determining study of oral niraparib in combination with ZEN003694 given daily in 28-day cycles will enroll patients with metastatic or recurrent solid cancer. Dose escalation will follow the mTPI-2/Keyboard design. Eligible patients will receive therapy until disease progression or unacceptable toxicities are experienced.

Start Date23 Jan 2024

Sponsor / Collaborator

University of Pittsburgh

[+2]

100 Clinical Results associated with ZEN-3694

100 Translational Medicine associated with ZEN-3694

100 Patents (Medical) associated with ZEN-3694

Literatures (Medical) associated with ZEN-3694

17 Apr 2024·Bioanalysis

An LC–MS/MS method for determination of the bromodomain inhibitor ZEN-3694 and its metabolite ZEN-3791 in human plasma

Article

Author: Feng, Ye ; Piekarz, Richard ; Mahdi, Haider ; Synold, Timothy W ; Beumer, Jan H

We have developed and validated a novel LC-MS/MS method for the simultaneous quantification of ZEN-3694 and its active metabolite ZEN-3791 in human plasma after protein precipitation. Stable isotope-labeled versions were used as internal standards. Chromatographic separation was achieved on a Kinetex C18 column using 0.1% formic acid in H₂O and 0.1% formic acid in MeOH as mobile phases. Detection was performed via positive electrospray ionization mode with multiple reaction monitoring. The assay exhibited linearity in the concentration range of 5-5000 ng/ml for both analytes. Intra- and inter-assay precision and accuracy were within ±11%. ZEN-3694 and ZEN-3791 recoveries were between 93 and 105%. This LC-MS/MS assay is an essential tool to study ZEN-3694 in an ongoing clinical trial (NCT04840589).

01 Jun 2022·Cancer gene therapyQ2 · MEDICINE

Combination of ZEN-3694 with CDK4/6 inhibitors reverses acquired resistance to CDK4/6 inhibitors in ER-positive breast cancer

Q2 · MEDICINE

Article

Author: Kharenko, Olesya A ; Patel, Reena G ; van der Horst, Edward H ; Calosing, Cyrus

CDK4/6 inhibitors significantly prolong progression-free survival in patients with advanced hormone receptor-positive (HR+) HER2-negative breast cancer. Despite recent successes, patients acquire resistance, necessitating the development of additional novel therapeutic strategies. Bromodomain and extra-terminal domain (BET) proteins are key epigenetic regulators that interact with acetylated lysine (AcLys) residues of histones or transcription factors. BET proteins are directly involved in modulating estrogen receptor (ER) signaling and the cell cycle. Therefore, BET inhibitors can potentially offer new strategies in the treatment of advanced ER+ breast cancer. ZEN-3694 is an orally bioavailable small molecule BET inhibitor currently being evaluated in Phase 1/2 clinical trials (NCT03901469). To assess a potential combination strategy in a CDK4/6i resistant breast cancer population, we investigated the mechanism of action of ZEN-3694 combined with CDK4/6 inhibitors in the ER+ cell lines resistant to palbociclib or abemaciclib. Here, we describe that the combination of ZEN-3694 with CDK4/6i potently inhibits proliferation and induces apoptosis in CDK4/6i resistant cell lines. The resistance to both palbociclib and abemaciclib was associated with the strong upregulation of CDK6 and CCND1 protein levels, which was reversed by the ZEN-3694 treatment. Furthermore, RNAseq data and pathway analysis elucidated the combinatorial effects of ZEN-3694 with CDK4/6 inhibitors through significant downregulation of multiple pathways involved in cell cycle regulation, cellular growth, proliferation, apoptosis, inflammation, and cellular immune response. Our data indicate that ZEN-3694 has therapeutic potential in combination with CDK4/6 inhibitors in patients with advanced ER+ breast resistant to CDK4/6 inhibitors.

15 Oct 2020·Clinical cancer research : an official journal of the American Association for Cancer ResearchQ1 · MEDICINE

A Phase Ib/IIa Study of the Pan-BET Inhibitor ZEN-3694 in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer

Q1 · MEDICINE

Article

Author: Campeau, Eric ; Aggarwal, Rahul R. ; Heath, Elisabeth I. ; Attwell, Sarah ; Bauman, Lisa ; Feng, Felix Y. ; Abida, Wassim ; Pantuck, Allan J. ; Nanus, David M. ; Schweizer, Michael T. ; Small, Eric J. ; Alumkal, Joshi J. ; Snyder, Margo ; Lakhotia, Sanjay ; Norek, Karen

Abstract:

Purpose::

ZEN-3694 is a bromodomain extraterminal inhibitor (BETi) with activity in androgen-signaling inhibitor (ASI)-resistant models. The safety and efficacy of ZEN-3694 plus enzalutamide was evaluated in a phase Ib/IIa study in metastatic castration-resistant prostate cancer (mCRPC).

Patients and Methods::

Patients had progressive mCRPC with prior resistance to abiraterone and/or enzalutamide. 3+3 dose escalation was followed by dose expansion in parallel cohorts (ZEN-3694 at 48 and 96 mg orally once daily, respectively).

Results::

Seventy-five patients were enrolled (N = 26 and 14 in dose expansion at low- and high-dose ZEN-3694, respectively). Thirty (40.0%) patients were resistant to abiraterone, 34 (45.3%) to enzalutamide, and 11 (14.7%) to both. ZEN-3694 dosing ranged from 36 to 144 mg daily without reaching an MTD. Fourteen patients (18.7%) experienced grade ≥3 toxicities, including three patients with grade 3 thrombocytopenia (4%). An exposure-dependent decrease in whole-blood RNA expression of BETi targets was observed (up to fourfold mean difference at 4 hours post–ZEN-3694 dose; P ≤ 0.0001). The median radiographic progression-free survival (rPFS) was 9.0 months [95% confidence interval (CI), 4.6–12.9] and composite median radiographic or clinical progression-free survival (PFS) was 5.5 months (95% CI, 4.0–7.8). Median duration of treatment was 3.5 months (range, 0–34.7+). Lower androgen receptor (AR) transcriptional activity in baseline tumor biopsies was associated with longer rPFS (median rPFS 10.4 vs. 4.3 months).

Conclusions::

ZEN-3694 plus enzalutamide demonstrated acceptable tolerability and potential efficacy in patients with ASI-resistant mCRPC. Further prospective study is warranted including in mCRPC harboring low AR transcriptional activity.

News (Medical) associated with ZEN-3694

10 Oct 2024

·www.prnewswire.com

Metastatic Castration-Resistant Prostate Cancer Clinical Trial Pipeline Appears Robust With 90+ Key Pharma Companies Actively Working in the Therapeutics Segment | DelveInsight

Metastatic Castration-Resistant Prostate Cancer (mCRPC) refers to prostate cancer that has spread (metastasized) to other parts of the body and continues to progress despite treatments that lower testosterone levels (androgen deprivation therapy or ADT) major pharmaceutical companies are heavily investing in research and development of new treatments, including immunotherapy (e.g., sipuleucel-T) and targeted therapies, which are seen as the next frontier in treating mCRPC. The use of precision medicine to identify genetic profiles in patients has further expanded the potential for targeted treatment. LAS VEGAS , Oct. 10, 2024 /PRNewswire/ -- DelveInsight's ' Metastatic Castration-Resistant Prostate Cancer Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mCRPC therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mCRPC pipeline domain. Key Takeaways from the Metastatic Castration-Resistant Prostate Cancer Pipeline Report DelveInsight's mCRPC pipeline report depicts a robust space with 90+ active players working to develop 100+ pipeline therapies for mCRPC treatment. Key mCRPC companies such as Regeneron Pharmaceuticals, AstraZeneca, Hinova Pharmaceuticals, Zenith Epigenetic, Eli Lilly and Company, Astellas Pharma, Seagen, Pfizer, Progenics Pharmaceutical, Molecular Insight Pharmaceuticals, Bayer, Accutar Biotechnology Inc, Hinova Pharmaceuticals, Forma Therapeutics, Inc., HALDA THERAPEUTICS INC., Tavanta Therapeutics, Lantheus, Pfizer, AB Science, Syntrix Pharmaceuticals, Exelixis, Laekna Therapeutics Shanghai Co. Ltd., Cardiff Oncology, Ipsen, Norroy Bioscience, Astellas Pharma, Novartis, Johnson & Johnson, Tempest Therapeutics, and others are evaluating new mCRPC drugs to improve the treatment landscape. Promising mCRPC pipeline therapies such as REGN 4336, Capivasertib, Deutenzalutamide, ZEN003694, Abemaciclib, Enfortumab vedotin, Talazoparib, I-131-1095, Pelgifatamab corixetan, AC176, HP518, FT-7051, HLD-0915, TAVT-45, PNT2002, Mevrometostat, Masitinib, SX-682, XL092, LAE001, Onvansertib, Tazemetostat, 177Lu-NYM032, PRL-02, 225 Actinium PSMA 617, ARX51, TPST-1120, and others are under different phases of mCRPC clinical trials. In October 2024, Curium announced that it had entered into a strategic partnership with PDRadiopharma Inc, a wholly-owned subsidiary of PeptiDream, for the clinical development, regulatory filing, and commercialization in Japan of 177Lu-PSMA-I&T and 64Cu-PSMA-I&T. The two agents 177Lu-PSMA-I&T and 64Cu-PSMA-I&T target prostate-specific membrane antigen (PSMA) expressed on prostate cancer cells and are being investigated for prostate cancer treatment and diagnostics. In July 2024, the US FDA granted fast-track designation to the prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical 225Ac-FL-020 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). In July 2024, Merck and Orion Corporation announced the mutual exercise of option providing Merck global exclusive rights to Opevesostat, an investigational CYP11A1 inhibitor, for the treatment of Metastatic Castration-Resistant Prostate Cancer. In July 2024, the US FDA granted fast-track designation to the antibody-drug conjugate (ADC) BNT324/DB-1311 to potentially treat patients with unresectable advanced or metastatic castration-resistant prostate cancer (mCRPC) whose disease had progressed on or after standard systemic regimens. In July 2024, FutureChem announced that the FC-705 has received orphan drug designation from the Ministry of Food and Drug Safety (MFDS) for the treatment of prostate cancer. In June 2024, CAR T-Cell Therapy demonstrated promising results for mCRPC according to Phase I trial results. In January 2024, Lava Therapeutics announced that it has signed a clinical trial collaboration and supply agreement with Merck to evaluate its prostate cancer therapy LAVA-1207 as a combination treatment with MSD's Keytruda (pembrolizumab). In July 2024, Blue Earth Therapeutics announced the signing of a clinical research collaboration with University College London (UCL). The collaboration is centered on a Phase I/II trial designed to evaluate the safety, tolerability, radiation dosimetry, and antitumor activity of the 225Ac-rhPSMA-10.1 in men with metastatic castrate-resistant prostate cancer who have previously responded to lutetium 177 (177Lu)-PSMA therapy. Request a sample and discover the recent advances in mCRPC treatment drugs @ Metastatic Castration-Resistant Prostate Cancer Pipeline Report The mCRPC pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mCRPC drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mCRPC clinical trial landscape. Metastatic Castration-Resistant Prostate Cancer Overview Metastatic castration-resistant prostate cancer (mCRPC) is an advanced stage of prostate cancer that continues to grow and spread despite hormone therapy aimed at lowering testosterone levels. The term "metastatic" refers to cancer spreading to other parts of the body, such as the bones, lymph nodes, or distant organs, while "castration-resistant" indicates that the cancer no longer responds to treatments that reduce testosterone, a key driver of prostate cancer growth. mCRPC is typically more aggressive and challenging to treat than earlier stages of prostate cancer. The causes of mCRPC stem from genetic and environmental factors. Genetic mutations in the androgen receptor pathway can make cancer cells less dependent on testosterone, allowing them to thrive even under hormone-suppressing treatments. Environmental factors like diet, lifestyle, and exposure to certain chemicals may also contribute to the development and progression of prostate cancer. Symptoms of mCRPC often include pain in bones, fatigue, difficulty urinating, weight loss, and general weakness. As the cancer spreads, it can impair the function of other organs, depending on the site of metastasis. Diagnosis of mCRPC usually involves a combination of tests, including prostate-specific antigen (PSA) blood tests, imaging studies like CT scans, MRIs, or bone scans, and sometimes biopsies to confirm the spread and resistance to treatment. Treatment options for mCRPC are more complex and may include newer hormonal therapies (e.g., abiraterone, enzalutamide), chemotherapy (docetaxel or cabazitaxel), immunotherapy (e.g., sipuleucel-T), or targeted therapies such as PARP inhibitors. Bone-targeting therapies, radiation, and palliative care can also be used to manage symptoms and improve the quality of life. Treatment is typically tailored to the individual based on the extent of the disease and the patient health. Find out more about mCRPC treatment drugs @ Drugs for Metastatic Castration-Resistant Prostate Cancer Treatment A snapshot of the mCRPC Pipeline Drugs mentioned in the report: Learn more about the emerging mCRPC pipeline therapies @ Metastatic Castration-Resistant Prostate Cancer Clinical Trials Metastatic Castration-Resistant Prostate Cancer Therapeutics Assessment The mCRPC pipeline report proffers an integral view of the mCRPC emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Metastatic Castration-Resistant Prostate Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous Therapeutics Assessment By Molecule Type: Small molecule, Cell therapy, Peptides, Polymer, Small molecule, Gene therapy Therapeutics Assessment By Mechanism of Action: Androgen receptor degradation enhancers, Antibody-dependent cell cytotoxicity, Proto-oncogene protein c-akt inhibitors, Androgen receptor antagonists, Bromodomain and extraterminal domain protein inhibitors, Cyclin-dependent kinase 4 inhibitors, Cyclin-dependent kinase 6 inhibitors, Ionizing radiation emitters, PPAR alpha antagonists. Key Metastatic Castration-Resistant Prostate Cancer Companies: Regeneron Pharmaceuticals, AstraZeneca, Hinova Pharmaceuticals, Zenith Epigenetic, Eli Lilly and Company, Astellas Pharma, Seagen, Pfizer, Progenics Pharmaceutical, Molecular Insight Pharmaceuticals, Bayer, Accutar Biotechnology Inc, Hinova Pharmaceuticals, Forma Therapeutics, Inc., HALDA THERAPEUTICS INC., Tavanta Therapeutics, Lantheus, Pfizer, AB Science, Syntrix Pharmaceuticals, Exelixis, Laekna Therapeutics Shanghai Co. Ltd., Cardiff Oncology, Ipsen, Norroy Bioscience, Astellas Pharma, Novartis, Johnson & Johnson, Tempest Therapeutics, and others. Key Metastatic Castration-Resistant Prostate Cancer Pipeline Therapies: REGN 4336, Capivasertib, Deutenzalutamide, ZEN003694, Abemaciclib, Enfortumab vedotin, Talazoparib, I-131-1095, Pelgifatamab corixetan, AC176, HP518, FT-7051, HLD-0915, TAVT-45, PNT2002, Mevrometostat, Masitinib, SX-682, XL092, LAE001, Onvansertib, Tazemetostat, 177Lu-NYM032, PRL-02, 225 Actinium PSMA 617, ARX51, TPST-1120, and others. Dive deep into rich insights for new drugs for mCRPC treatment, visit @ Metastatic Castration-Resistant Prostate Cancer Drugs Table of Contents For further information on the mCRPC Cancer pipeline therapeutics, reach out @ Metastatic Castration-Resistant Prostate Cancer Treatment Drugs Related Reports Metastatic Castration-Resistant Prostate Cancer Market Metastatic Castration-Resistant Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCRPC companies including AstraZeneca, Merck Sharp & Dohme, Hinova Pharmaceuticals, Pfizer, Astellas Pharma, Modra Pharmaceuticals, AB Science, Eli Lilly and Company, Zr Pharma & GmbH, Bristol-Myers Squibb, Ipsen, Exelixis, Takeda, Janssen Research & Development, Tesaro, Lantheus Holdings, Kintor Pharmaceutical, MacroGenics, Daiichi Sankyo, Madison Vaccines, Novartis, Point Biopharma, Xencor, Essa Pharma, Telix International, Bayer, Arvinas, among others. Metastatic Prostate Cancer Market Metastatic Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key metastatic prostate cancer companies including AstraZeneca, Arvinas, Madison Vaccines, Phosplatin Therapeutics, Hinova Pharmaceuticals, Bristol Myers Squibb, Merck, MacroGenics, Daiichi Sankyo, Seagen, Taiho Pharmaceutical, Modra Pharmaceuticals, Xencor, Point Biopharma, Lantheus Holdings, Zenith Epigenetics, Essa Pharma, Telix Pharmaceuticals, Kintor Pharmaceutical, AB Science, Eli Lilly and Company, Exelixis among others. Metastatic Castration-Sensitive Prostate Cancer Market Metastatic Castration-Sensitive Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCSPC companies including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. Metastatic Castration-Sensitive Prostate Cancer Pipeline Metastatic Castration-Sensitive Prostate Cancer Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key mCSPC companies, including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Fast TrackImmunotherapyPhase 1Clinical Result

29 Feb 2024

·www.biospace.com

Zenith Epigenetics Proudly Supports Rare Disease Day

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

Clinical Study

26 Oct 2023

·www.biospace.com

Zenith Epigenetics Ltd. Announces Collaboration with Cencora on ZEN-3694

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

Phase 2Phase 1Immunotherapy

100 Deals associated with ZEN-3694

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fallopian Tube Carcinoma	Phase 2	United States	Pfizer Inc.	13 Apr 2023
Fallopian Tube Carcinoma	Phase 2	United States	Zenith Epigenetics Ltd.	13 Apr 2023
Primary peritoneal carcinoma	Phase 2	United States	Zenith Epigenetics Ltd.	13 Apr 2023
Primary peritoneal carcinoma	Phase 2	United States	Pfizer Inc.	13 Apr 2023
Recurrent ovarian cancer	Phase 2	United States	Zenith Epigenetics Ltd.	13 Apr 2023
Recurrent ovarian cancer	Phase 2	United States	Pfizer Inc.	13 Apr 2023
Recurrent Primary Peritoneal Carcinoma	Phase 2	United States	Zenith Epigenetics Ltd.	13 Apr 2023
Recurrent Primary Peritoneal Carcinoma	Phase 2	United States	Pfizer Inc.	13 Apr 2023
Advanced Lymphoma	Phase 2	United States	National Cancer Institute	16 Nov 2022
B-cell lymphoma refractory	Phase 2	United States	National Cancer Institute	16 Nov 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04471974 (ESMO2022) Manual	Phase 2	Metastatic castration-resistant prostate cancer MSI-High	22	ZEN-3694+enzalutamide+pembrolizumab	fwbabhsqnt(sngwqjkeow) = ZEN 72 mg daily + ENZ 160 mg/day + P 200 mg IV q 3 weeks fnietojjll (ggcbmmrqzo ) View more	Positive	10 Sep 2022
NCT03901469 (ASCO2022) Manual	Phase 1/2	Triple Negative Breast Cancer ER Negative \| PR Negative \| HER2 Negative	51	ZEN-3694+talazoparib	gbyjhtjmym(obcddvfpzm) = RP2D was determined to be 48mg qd ZEN-3694 plus 0.75mg qd talazoparib. zgykdybort (dyhocfenfr ) View more	Positive	02 Jun 2022
NCT03901469 (ASCO2022) Manual	Phase 1/2		51	ZEN-3694+talazoparib (TNBC at diagnosis patients)		Positive	02 Jun 2022
SABCS2021	Phase 1/2	Triple Negative Breast Cancer wild-type BRCA1/2	15	ZEN003694 48mg + Talazoparib 1mg	lcxnsjswli(jwcqvtolff) = zzddftpjed zmeauqpchp (pvbxzmwern ) View more	Positive	15 Feb 2021
NCT02711956 (Pubmed \| Clin Cancer Res) Manual	Phase 1/2	Metastatic castration-resistant prostate cancer	75	Enzalutamide+ZEN-3694	qnhvhblhgl(skaledmpiw) = xctwgvclxl aksrhaqctc (qvwvumbsgp ) View more	Positive	15 Oct 2020

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