Neurofibrosarcoma

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

Combining a pair of experimental drugs may help treat malignant peripheral nerve sheath tumors with fewer harmful side effects, according to preliminary animal studies. Combining a pair of experimental drugs may help treat malignant peripheral nerve sheath tumors with fewer harmful side effects, according to preliminary animal studies led by investigators at the Johns Hopkins Kimmel Cancer Center and Johns Hopkins Drug Discovery. The study, published Dec. 1 in the journal Molecular Cancer Therapeutics, shows that combining an experimental drug that blocks the metabolism of the amino acid glutamine with a second experimental drug that blocks recycling of purines (building blocks of the genetic material DNA and RNA that tumors need to proliferate) reduced the size of peripheral nerve sheath tumors in mice and increased their rates of survival. The combination was less toxic than previously tested drug combinations. "Using these broadly active metabolic inhibitors can help us better understand how these tumors are using nutrients to build what they need to make more tumor cells," says lead study author Kathryn Lemberg, M.D., Ph.D., an assistant professor of oncology at Johns Hopkins. Malignant peripheral nerve sheath tumors (MPNST) are rare cancers that originate in the lining of the nerves. Individuals with the cancer predisposition syndrome neurofibromatosis type 1 (NF1) have an elevated risk of these cancers. MPNST are the leading cause of death in people with NF1 under the age of 40, Lemberg explains. "When patients with NF1 develop these tumors, there is, unfortunately, a risk of poor outcome based on whether the tumor can be completely surgically removed, whether it responds to conventional chemotherapy, and how widespread the cancer is," Lemberg says. "We need better treatments for these tumors." Barbara Slusher, Ph.D., M.A.S., director of Johns Hopkins Drug Discovery and senior author on the study, and colleagues developed the glutamine antagonist JHU395 that blocks the utilization of glutamine. JHU395 is particularly well-suited for blocking glutamine metabolism in nerve-associated tissues. "Glutamine is a building block for proteins and many other large molecules that cancer cells need to grow, proliferate, survive and potentially spread," Lemberg says. Previous studies by Lemberg, Slusher and colleagues showed that treatment of mouse MPNST with JHU395 yields a partial tumor reduction. The drug works by impairing one arm of purine production, the "de novo" pathway. However, with JHU395 treatment, the tumors can still access purine by a recycling or salvage pathway. Combining JHU395 with the classical purine antimetabolite 6-mercaptopurine (6-MP) produces a better anti-tumor response because 6-MP itself can cause liver and gastrointestinal toxicity based on the way the body metabolizes it to the active form. Lemberg, Slusher and colleagues from the Institute of Organic Chemistry and Biochemistry (IOCB) of the Czech Academy of Sciences in Prague developed an alternate purine salvage-blocking prodrug called Pro-905. In experiments conducted in collaboration with scientists at Northwestern University, they showed that JHU395 and Pro-905 inhibit purine synthesis in human MPNST cells by distinct mechanisms, leading to decreased synthesis of new DNA and RNA. In mouse models of the condition, they found that Pro-905 in combination with JHU395 reduced tumor growth more effectively than 6-MP and with less toxicity. "Collaboration is key to moving science forward, particularly for studies of rare tumor types that require the expertise of multiple researchers," Lemberg says. Now, Lemberg and colleagues want to see if this experimental drug combination is also effective in other types of tumors that use similar pathways to grow. They also want to test whether this combination might be effective in patients with malignant peripheral nerve sheath tumors or if Pro-905 might be used as maintenance therapy to prevent tumor regrowth, as 6-MP is. Lemberg also plans to collaborate with other Johns Hopkins researchers to determine if starving the tumors of glutamine and purines might also enable the immune system to kick in and fight the tumor. Earlier research of JHU395 showed that cancer cells steal nutrients, including glutamine, to maintain their survival, starving surrounding cells such as immune cells. Using JHU395 to cut cancer cells off from their supply of glutamine strengthens immune cells, invigorating their response to cancer, Slusher says. "Building on observations from one study and keeping the science moving forward can open up a lot of potential routes for future therapies for diseases that need better treatment options," Lemberg says. Study co-authors were Joanna Marie H. Aguilar, Jesse Alt, Diane E. Peters, Liang Zhao, Ying Wu, Naziba Nuha, Verena Staedtke, Christine A. Pratilas and Rana Rais of Johns Hopkins. Other investigators were from Northwestern University Feinberg School of Medicine in Chicago, Institute of Organic Chemistry and Biochemistry (IOCB) of the Czech Academy of Sciences in Prague, and Beth Israel Deaconess Medical Center in Boston. The study was supported by a CureSearch for Children's Cancer Young Investigator Award, a Maryland Innovation Initiative Award, an Allegheny Health Network Award, and the National Institutes of Health (grant R01CA229451). Lemberg and Slusher hold a patent on prodrugs of 6-mercaptopurine. Slusher and Rais are co-inventors on Johns Hopkins University patents covering novel glutamine antagonist prodrugs and their utility. These patents have been licensed to Dracen Pharmaceuticals, Inc. Slusher and Rais are also co-founders of and hold equity in Dracen Pharmaceuticals. These arrangements have been reviewed and approved by The Johns Hopkins University in accordance with its conflict-of-interest policies.

– Data support the ongoing clinical development of TNG908 and TNG462 PRMT5 inhibitors for the treatment of MTAP-deleted cancers – BOSTON, Mass., Nov. 13, 2023 (GLOBE NEWSWIRE) -- Tango Therapeutics, Inc. (NASDAQ: TNGX), a clinical-stage biotechnology company committed to discovering and delivering the next generation of precision cancer medicines, today announced that two abstracts have been selected for poster presentations at the Society for Neuro-Oncology (SNO) 28th Annual Meeting taking place November 15-19, 2023, in Vancouver, Canada. “As we advance TNG908 and TNG462, our two MTA-cooperative PRMT5 inhibitors, in phase 1/2 clinical trials, we are pleased to share preclinical data at SNO that affirm their potential as new therapies for patients with MTAP-deleted cancers, including glioblastoma and malignant peripheral nerve sheath tumors,” said Barbara Weber, M.D., President and Chief Executive Officer of Tango Therapeutics. “TNG908 demonstrates strong antitumor activity in MTAP-deleted glioblastoma models. Additionally, data from preclinical malignant peripheral nerve sheath tumor models evaluating TNG908 and TNG462 demonstrate efficacy at well-tolerated doses. TNG462 is potentially best-in-class. Dose escalation of TNG908 and TNG462 in phase 1/2 trials is ongoing.” Abstracts accepted for poster presentation Title: TNG908, a brain-penetrant MTA-cooperative PRMT5 inhibitor, is efficacious in preclinical MTAP-deleted models including glioblastomaPoster #: DDDR-33Presenter: Minjie Zhang, Ph.D., Associate Director, Pharmacology, Tango TherapeuticsDate and Time: Friday, November 17, 2023; 7:30 – 9:30 p.m. PT Glioblastoma (GBM), the most common malignant primary brain tumor in adults, has a poor prognosis and represents a significant unmet need for more effective therapies. TNG908, a clinical stage MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted solid tumors, is shown to be brain penetrant and drives strong antitumor activity in preclinical models of MTAP-deleted GBM. Title: MTA-cooperative PRMT5 inhibitors are efficacious in MTAP-deleted malignant peripheral nerve sheath tumor modelsPoster #: EXTH-63Presenter: Xiaochun Zhang, M.D., Staff Scientist, Hirbe Lab, Washington University School of Medicine in St. LouisDate and Time: Friday, November 17, 2023; 7:30 – 9:30 p.m. PT Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas with limited treatment options and poor survival rates. The clinical stage MTA-cooperative PRMT5 inhibitors TNG908 and TNG462 are efficacious in MPNST preclinical models and represent potential new therapeutic strategies for patients with MTAP-deleted MPNST. Abstract titles, presentation information and text are currently available to the public in the 2023 abstract supplement to SNO’s official journal, Neuro-Oncology. About Tango Therapeutics Tango Therapeutics is a clinical-stage biotechnology company dedicated to discovering novel drug targets and delivering the next generation of precision medicine for the treatment of cancer. Using an approach that starts and ends with patients, Tango leverages the genetic principle of synthetic lethality to discover and develop therapies that take aim at critical targets in cancer. This includes expanding the universe of precision oncology targets into novel areas such as tumor suppressor gene loss and their contribution to the ability of cancer cells to evade immune cell killing. For more information, please visit www.tangotx.com. Forward-Looking Statements Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events, Tango’s future operating performance and goals, the anticipated benefits of therapies and combination therapies (that include a Tango pipeline product), expectations, beliefs and development objectives for Tango’s product pipeline and clinical trials. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “goal”, “estimate”, “anticipate”, “believe”, “committed” “predict”, “designed,” “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology. For example, implicit or explicit statements concerning the following include or constitute forward-looking statements: the data presented at SNO supports the ongoing clinical development of the Company’s PRMT5 inhibitors for the treatment of MTAP-deleted cancers; the Company is committed to discovering and delivering the next generation of precision cancer medicines; the preclinical data presented at SNO affirm TNG908’s and TNG462’s potential as new therapies for patients for MTAP-deleted cancers, including glioblastoma and malignant peripheral nerve sheath tumors; TNG462 is potentially best-in-class; dose escalation of TNG908 and TNG462 is ongoing; TNG908 and TNG462 represent potential new therapeutic strategies for patients with MTAP-deleted MPNST; the expected timing of: (i) development candidate declaration for certain targets, (ii) initiating IND-enabling studies; (iii) filing INDs; (iv) clinical trial initiation and (v) disclosing initial, interim and final clinical trial results; and the expected benefits of the Company's development candidates and other product candidates. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Tango and its management, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: benefits of product candidates seen in preclinical analyses may not be evident when tested in later pre-clinical studies or in clinical trials or when used in broader patient populations (if approved for commercial sale); Tango has limited experience conducting clinical trials (and will rely on a third party to operate its clinical trials) and may not be able to commence the clinical trial (including opening clinical trial sites, dosing the first patient, and enrolling and dosing an adequate number of clinical trial participants) when expected, may not be able to continue dose escalation on anticipated timelines, and may not generate results (including final or initial safety, efficacy data and proof-of-mechanism and proof-of-concept) in the anticipated timeframe (or at all); Tango’s pipeline products may not be safe and/or effective in humans; Tango has a limited operating history and has not generated any revenue to date from product sales, and may never become profitable; other companies may be able to identify and develop product candidates more quickly than the Company and commercially introduce the product prior to the Company; the Company’s proprietary discovery platform is novel and may not identify any synthetic lethal targets for future development; the Company may not be able to identify development candidates on the schedule it anticipates due to technical, financial or other reasons; the Company may not be able to file INDs for development candidates on time, or at all, due to technical or financial reasons or otherwise; the Company may utilize cash resources more quickly than anticipated; Tango will need to raise capital in the future and if we are unable to raise capital when needed or on attractive terms, we would be forced to delay, scale back or discontinue some of our development programs or future commercialization efforts (which may delay filing of INDs, dosing patients, reporting clinical trial results and filing new drug applications); Tango’s approach to the discovery and development of product candidates is novel and unproven, which makes it difficult to predict the time, cost of development, and likelihood of successfully developing any products; Tango may not identify or discover additional product candidates or may expend limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success; the Company’s product candidates may cause adverse or other undesirable side effects (or may not show requisite efficacy) that could, among other things, delay or prevent regulatory approval; our dependence on third parties for conducting clinical trials and producing drug product; our ability to obtain and maintain patent and other intellectual property protection for our technology and product candidates or the scope of intellectual property protection obtained is not sufficiently broad; and delays and other impacts on product development and clinical trials from the COVID-19 pandemic. Additional information concerning risks, uncertainties and assumptions can be found in Tango’s filings with the SEC, including the risk factors referenced in Tango’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, as supplemented and/or modified by its most recent Quarterly Report on Form 10-Q. You should not place undue reliance on forward-looking statements in this presentation, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Tango specifically disclaims any duty to update these forward-looking statements. Investor Contact:Sam Martin/Andrew VulisArgot Partnerstango@argotpartners.com Media Contact:Amanda Brown GalgaySVP, Corporate Communications, Tango Therapeuticsmedia@tangotx.com