Neurofibrosarcoma

Poster Includes Preclinical Data on Novel Direct Pan-RAS Inhibitors CARLSBAD, Calif., April 10, 2024 (GLOBE NEWSWIRE) -- Qualigen Therapeutics, Inc. (“Qualigen” or “the Company,” Nasdaq: QLGN) today announces a poster presentation on its preclinical Novel Direct Pan-RAS Inhibitors was presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 held April 5 – 10 in San Diego, California. “We continue to see cancers developing resistance to current clinical agents that target a particular K-RAS mutation, and we remain optimistic that a more broad-based Pan-RAS inhibitor may help resolve these issues”, commented Michael Poirier, Qualigen’s Chairman and Chief Executive Officer. “The data show that our Pan-RAS inhibitors can interfere with K-RAS, H-RAS and N-RAS activity and signaling, on both mutant and wild type RAS. This suggests there could be a viable window for Pan-RAS inhibitors in patients with RAS driven tumors, as well as a potentially broader application to cancers not usually associated with RAS, such as certain classes of Ovarian, Breast, and NF1 loss driven Malignant Peripheral Nerve Sheath Tumors (MPNST).” The Annual AACR Conference is a focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine. Highlights from this Poster Abstract #3320 - “Novel Direct Pan-RAS Inhibitors" - Howard Donninger, Rachel Ferril, Becca von Baby, Joe Burlison, Mike Sabo, Tariq Arshad, Rob Monsen, John Trent, and Geoffrey J. Clark - Results demonstrated the compounds' role as Pan-RAS inhibitors. These compounds effectively target and disrupt the activity and signaling of various RAS mutations, including K-RAS, H-RAS, and N-RAS, impacting both mutant and wild type variants. Encouragingly, in vivo studies indicate minimal toxicity associated with these compounds, likely due to their selective suppression of RAS signaling at the administered doses. These results hint at a promising therapeutic potential for Pan-RAS inhibitors in clinical settings, emphasizing their significance in cancer treatment strategies. About Pan-RAS Qualigen Therapeutics has collaborated with Dr. Geoff Clark and Dr. Joe Burlison at the University of Louisville, Kentucky to develop a series of potentially highly potent compounds to take forward into preclinical development. Lead compounds are believed to suppress or block the interaction of endogenous RAS with c-RAF, and thereby influence the K-RAS, H-RAS, and N-RAS effector pathways. RAS acts as a “hub” that activates multiple effector pathways, hence blocking any single pathway may be ineffective for many RAS-driven tumor types, including pancreatic, lung, and colorectal cancers. This approach could potentially enable a differentiated, pan-RAS strategy for inhibiting the MAPK, PI3K, and RAL pathways implicated in cancer cell proliferation, survival, and differentiation. About Qualigen Therapeutics, Inc. Qualigen Therapeutics, Inc. is an early-clinical-stage biotechnology company. Until the sale of its diagnostic business in 2023, Qualigen had a 20+ year history developing, marketing and selling medical devices in the United States and internationally. Our investigational QN-302 compound is a small molecule selective transcription inhibitor with strong binding affinity to G4s prevalent in cancer cells; such binding could, by stabilizing the G4s against “unwinding,” help inhibit cancer cell proliferation. QN-302 is currently in a Phase 1a clinical trial. The preclinical compounds within Qualigen’s family of PAN-RAS oncogene protein-protein interaction inhibitor small molecules are believed to inhibit or block the binding of mutated RAS genes’ proteins to their effector proteins, thereby leaving the proteins from the mutated RAS unable to cause further harm. In theory, such mechanism of action may be effective in the treatment of about one quarter of all cancers, including certain forms of pancreatic, colorectal, and lung cancers. For more information about Qualigen Therapeutics, Inc., please visit www.qlgntx.com. Contact: Michael PoirierQualigen Therapeutics, Inc.760.452.8111mpoirier@qlgntx.com Source: Qualigen Therapeutics, Inc.

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.