Rhabdoid Tumor

LP-184 is the first of Lantern’s drug candidates developed by leveraging Lantern’s AI platform, RADR® US FDA previously granted LP-184 Rare Pediatric Disease Designation and Orphan Drug Designation (ODD) for the treatment of pediatric patients with ATRT DALLAS--(BUSINESS WIRE)-- Lantern Pharma, Inc. (NASDAQ: LTRN), an artificial intelligence (AI) company developing targeted and transformative cancer therapies using its proprietary RADR® AI and machine learning (ML) platform with multiple clinical-stage drug programs, received a notice of allowance from the United States Patent and Trademark Office (USPTO) covering a method of treatment for Atypical Teratoid Rhabdoid Tumor (ATRT) using LP-184, an aggressive and rapidly growing form of cancer of the central nervous system (CNS). “This patent allowance further fortifies Lantern Pharma's intellectual property portfolio, providing us with an additional layer of protection for our potential blockbuster LP-184 program, which is being developed for multiple targeted oncology indications, including ATRT in pediatric patients,” said Panna Sharma, CEO of Lantern Pharma. “Historically, pediatric ATRT has been treated with a combination of surgery, radiation, and chemotherapy, but unfortunately, these approaches have often resulted in unfavorable long-term outcomes for the children affected.” Drs. Kosj and Jaymi Yamoah, Co-founders of Hope4ATRT, a research entity dedicated to directing resources and research to families in the fight against ATRT, commented, “As parents of a child who did not survive ATRT, we are compelled to advocate for more effective and less toxic treatment options for children still in this battle, and we are always thrilled to see progress in ATRT research. The work by Lantern scientists to rapidly develop new therapies with potential to treat ATRT brings us hope for the future.” Sharma continued, “The urgent need for new treatment options for pediatric brain cancers cannot be overstated. Our in-silico and in-vivo observations indicate that LP-184 has the potential to become an essential part of the treatment options for these patients, and this patent allowance provides a further assurance of protection for our advances in the treatment of this devastating disease.” LP-184 is the first of Lantern’s drug candidates developed by leveraging Lantern’s AI and ML platform, RADR®, to advance to a first-in-human Phase 1 basket trial. Lantern has rapidly advanced the clinical development of LP-184, activated the initial clinical trial sites, and has begun screening patients. Indications for the LP-184 trial are anticipated to include relapsed/refractory advanced pancreatic cancer, glioblastoma (GBM), brain metastases (brain mets), and multiple other recurring, advanced solid tumors with DNA damage response deficiencies. The dosage and safety data obtained in the Phase 1 trial will be used to advance the CNS indications, including ATRT, for a future Phase 2 trial to be sponsored by Lantern’s wholly-owned subsidiary, Starlight Therapeutics Inc. Globally, the aggregate annual market potential of LP-184’s target indications is estimated to be approximately $10+ billion, consisting of $5+ billion for CNS cancers and $6+ billion for other solid tumors. The U.S. Food and Drug Administration (FDA) has previously granted LP-184 Rare Pediatric Disease Designation and Orphan Drug Designation (ODD) for the treatment of pediatric patients with ATRT. The FDA has also previously granted LP-184 ODD for the treatment of pancreatic cancer and for the treatment of malignant glioma, including GBM. A notice of allowance is issued after the USPTO determines that the prosecution on the merits of a patent has been completed and grants the patent upon payment of the patent issuance fee. Additional corresponding patent applications are pending in Europe, Japan, Canada, and Australia. About ATRT ATRT is an aggressive and rare form of cancer of the central nervous system that predominantly affects children under the age of three. The National Cancer Institute (NCI) classifies ATRT as Grade IV tumors, meaning they are malignant (cancerous), aggressive, and fast-growing. The root genetic cause of ATRTs is attributed to bi-allelic mutations that inactivate either SMARCB1 (also known as INI1) or SMARCA4. Approximately 90 percent of pediatric ATRTs can be attributed to alterations in the SMARCB1 gene. SMARCB1 was included among several genes whose expression negatively correlated with LP-184 sensitivity in tumors. This in silico correlation was confirmed by in vitro and in vivo assessments of LP-184 in ATRT, with the highest potency of LP-184 in vivo having been seen in ATRT xenografts. About Lantern Pharma: Lantern Pharma (NASDAQ: LTRN) is an AI company transforming the cost, pace, and timeline of oncology drug discovery and development. Our proprietary AI and machine learning (ML) RADR® platform leverages over 34 billion oncology-focused data points and a library of 200+ advanced ML algorithms to help solve billion-dollar, real-world problems in oncology drug development. By harnessing the power of AI and with input from world-class scientific advisors and collaborators, we have accelerated the development of our growing pipeline of therapies including eleven cancer indications and an antibody-drug conjugate (ADC) program. On average, our newly developed drug programs have been advanced from initial AI insights to first-in-human clinical trials in 2-3 years and at approximately $1.0-2.0 million per program. Our lead development programs include two Phase 2 clinical programs and multiple upcoming Phase 1 clinical trials anticipated for 2023. We have also established a wholly-owned subsidiary, Starlight Therapeutics Inc., to focus exclusively on the clinical execution of our promising therapies for CNS and brain cancers, many of which have no effective treatment options. Our AI-driven pipeline of innovative product candidates is estimated to have a combined annual market potential of over $15 billion USD and have the potential to provide life-changing therapies to hundreds of thousands of cancer patients across the world. Please find more information at: Website: LinkedIn: X/Twitter: @lanternpharma Newsletter – The Spark: Sign-up here Forward-looking Statements: This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include, among other things, statements relating to: future events or our future financial performance; the potential advantages of our RADR® platform in identifying drug candidates and patient populations that are likely to respond to a drug candidate; our strategic plans to advance the development of our drug candidates and antibody drug conjugate (ADC) development program; estimates regarding the development timing for our drug candidates and ADC development program; expectations and estimates regarding clinical trial timing and patient enrollment; our research and development efforts of our internal drug discovery programs and the utilization of our RADR® platform to streamline the drug development process; our intention to leverage artificial intelligence, machine learning and biomarker data to streamline and transform the pace, risk and cost of oncology drug discovery and development and to identify patient populations that would likely respond to a drug candidate; estimates regarding patient populations, potential markets and potential market sizes; sales estimates for our drug candidates and our plans to discover and develop drug candidates and to maximize their commercial potential by advancing such drug candidates ourselves or in collaboration with others. 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There are a number of important factors that could cause our actual results to differ materially from those indicated by the forward-looking statements, such as (i) the risk that our research and the research of our collaborators may not be successful, (ii) the risk that none of our product candidates has received FDA marketing approval, and we may not be able to successfully initiate, conduct, or conclude clinical testing for or obtain marketing approval for our product candidates, (iii) the risk that no drug product based on our proprietary RADR® AI platform has received FDA marketing approval or otherwise been incorporated into a commercial product, and (iv) those other factors set forth in the Risk Factors section in our Annual Report on Form 10-K for the year ended December 31, 2022, filed with the Securities and Exchange Commission on March 20, 2023. You may access our Annual Report on Form 10-K for the year ended December 31, 2022 under the investor SEC filings tab of our website at or on the SEC's website at . Given these risks and uncertainties, we can give no assurances that our forward-looking statements will prove to be accurate, or that any other results or events projected or contemplated by our forward-looking statements will in fact occur, and we caution investors not to place undue reliance on these statements. All forward-looking statements in this press release represent our judgment as of the date hereof, and, except as otherwise required by law, we disclaim any obligation to update any forward-looking statements to conform the statement to actual results or changes in our expectations.

Scientists have determined how the SWI/SNF chromatin remodeling complex helps cancer cells 'remember' how to be cancerous after division. When a cell divides, it retains information about how to grow and instructions about what type of cell to become. Scientists at St. Jude Children's Research Hospital have gained a new understanding of how these processes can work, revealing a previously unappreciated role for the SWI/SNF chromatin remodeling complex. The study was published today in Nature. When a cell undergoes differentiation, stem cells (the earliest cells that develop) undergo changes that transform them into a different type of cell, typically one with a more specialized function (such as a skin or muscle cell). As cells divide, they must retain the "memory" of their current differentiation state to transfer the proper identity to the daughter cells. Chromatin is a complex of DNA and protein tightly compacted inside cells. Chromatin must unwind to turn genes on and off in closely regulated processes. SWI/SNF complexes control a cell's identity during differentiation by changing chromatin architecture to regulate gene expression. However, it was unknown whether SWI/SNF complexes contribute to the memory of cell identity during cell division. Cancers often carry mutations that affect the SWI/SNF chromatin remodeling complex. One example is the loss of the core subunit SMARCB1. Other studies have also linked mutations in the complex to neurodevelopmental disorders. In this study, scientists at St. Jude have discovered how subunits of SWI/SNF act as "bookmarks" during mitosis to safeguard cell identity during division. The work points to the importance of SWI/SNF core subunits SMARCE1 and SMARCB1 and their roles in the process. "This work provides an understanding of a new component of mitotic memory, as well as provides clues to why a mutation of this SWI/SNF complex subunit would disrupt memory of what a cell should normally be doing and allow it to go into a cancerous state," said senior author Charles W.M. Roberts, M.D., Ph.D., Executive Vice President and St. Jude Comprehensive Cancer Center director. SWI/SNF subunits help cells "remember" Previously, researchers believed the enzymatically active subunit of the SWI/SNF complex was not bound to DNA in mitosis, so scientists have assumed that SWI/SNF complexes had no role during mitosis. In launching this study, Roberts wondered, "If a piece of this complex is mutated, how can a cancer cell remember to be a cancer cell coming out on the other side of mitosis? What is the memory mechanism sustaining the cancer cell?" Surprisingly, Roberts's team found that two individual subunits of SWI/SNF complexes, but not the rest of the complex, bind to mitotic DNA. They then showed that the binding of SMARCE1 and SMARCB1 is required for the appropriate reactivation of bound genes after mitosis. Further experiments, which removed SMARCE1 during mitosis, found that loss of SMARCE1 disrupts gene expression, impairs the ability of some other "bookmarks" to bind to their targets and causes abnormal neural differentiation. These findings suggest that SMARCE1 plays a mitotic bookmarking role and is essential for the retention of appropriate differentiation programming during mitosis. "In a normal cell, SMARCB1 would be bound in mitosis to bookmark the genes that should be turned on after the cell divides," Roberts said. "But SMARCB1 is deleted in nearly all cases of a highly lethal type of cancer that strikes young children called rhabdoid tumors. Consequently cell identity genes fail to turn on immediately after a cell divides. This may be a key component that enables the cells to stay in a cancerous state, as they fail to activate the genes that normally help them differentiate." Implications beyond pediatric cancer Previous work showed that SWI/SNF subunit abnormalities exist in approximately 20% of all cancers. Additionally, research has identified SWI/SNF subunit mutations in several types of neurodevelopmental diseases. "History has shown that genes that mutate in the earliest onset cancers, in babies and toddlers, are often a bit of a 'canary in a coal mine' for broader principles in cancer." Roberts said. "Indeed, while it was studies of rhabdoid tumors in young children that first linked SWI/SNF complexes to cancer, we now know that genes that encode subunits of SWI/SNF complexes are mutated in 20% of all cancers. Studying rhabdoid tumors, thus, not only provides insight into these often fatal cancers of young children, it is quite informative about many types of cancer." "Unlike adult cancers, where many genes are mutated, and it is harder to figure out what any single abnormality does, here we have a cancer driven by just this one mutation," Roberts added. "It's a beautiful model to understand how these processes work and then begin to leverage that understanding in adult cancers too." Authors and funding The study's co-first and co-corresponding author is Zhexin Zhu, formerly of the St. Jude Department of Oncology. The other co-first author is Xiaolong Chen, St. Jude Department of Computational Biology. Other authors are Ao Guo, Trishabelle Manzano, Patrick Walsh, Kendall Wills, Rebecca Halliburton, Sandi Radko-Juettner, Raymond Carter, Janet Partridge, Douglas Green and Jinghui Zhang of St. Jude. The work was part of the St. Jude Collaborative Research Consortium on Chromatin Regulation in Pediatric Cancer. Through the collaborative, investigators at different institutions conduct research that requires the expertise of scientists with various specialties, streamlining and speeding up progress. The study was also supported by the National Institutes of Health (R01CA216391, R01 AI123322), the National Cancer Institute (NCI) Cancer Center Support Grant (CCSG 2 P30 CA021765), NCI grants (R01CA113794 and R01CA172152), CURE AT/RT Now, Garret B. Smith Foundation, the Ruth L. Kirschstein National Research Service Award (F31 CA261150) and ALSAC, the fundraising and awareness organization of St. Jude.

SYDNEY, April 4, 2023 /PRNewswire/ -- Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, is pleased to announce the presentation of new data for both of its pipeline molecules, paxalisib and EVT801, at the upcoming Annual Meeting of the American Association for Cancer Research (AACR), held in Orlando, FL, from 14 – 19 April 2023. In total, there will be five presentations at AACR, four of which build on previous positive data for paxalisib in melanoma and childhood brain cancer. The new data being presented provide significant support and direction for the future development of paxalisib in these expansion indications. In addition, a presentation by scientists from Kazia's partner, Evotec, will outline the novel biomarker strategy employed in the phase I study of EVT801, and anticipates the potential initial clinical data from EVT801 in CY2023. Key Points Research by Dr Gennie Parkman and colleagues, working in the laboratory of Professor Sheri Holmen at the Huntsman Cancer Institute at the University of Utah in Salt Lake City, shows paxalisib leading to 'substantially increased overall survival' in a mouse model of BRAF-driven melanoma. Further data from Dr Tyler Findlay and Dr Kristen Malebranche in Professor Jeffery Rubens' team at Johns Hopkins University Medical School has shown compelling evidence of synergy between paxalisib and both gemcitabine, a chemotherapy agent, and mirdametinib, a targeted therapy, in animal models of atypical teratoid / rhabdoid tumors (AT/RT), a childhood brain cancer. This data expands on positive data for paxalisib as monotherapy and in other combination regimens that was presented at AACR in 2022. The results suggest potential therapeutic approaches for use in clinical trials. An additional abstract by Dr Hyuk Jean Kwon and colleagues at Professor Rubens' lab describes in vitro preclinical data for the combination of paxalisib with a dual inhibitor of ACVR1 and MEK in diffuse midline gliomas, a category of childhood brain cancers which includes DIPG. The data showed strong synergy between the two agents, and points to further research in this area. A poster presentation by Dr Michael Paillasse and colleagues at Evotec SE describes some of the novel biomarker selection strategies employed in the ongoing phase I study of EVT801 in advanced solid cancers (NCT05114668). The poster outlines the approaches taken by the Evotec team to identify VEGFR3 expression in a range of tissues, potentially allowing for the selection of clinical trial patients who are likely to be more responsive to EVT801. "The broad range of abstracts presented at AACR speak to the breadth of work that is ongoing across our pipeline," said Dr James Garner, Chief Executive Officer of Kazia. "The promising new data from Professors Holmen and Rubens, in melanoma and childhood brain cancer respectively, reinforces the significance of these new opportunities for paxalisib. Moreover, Kazia's ongoing collaboration with Evotec remains extremely fruitful, with excellent work from the biomarker team opening the possibility of rational patient selection in clinical trials. Of note, biomarker strategy is an important area of focus for FDA, and drug candidates with biomarker selection are potentially more likely to achieve approval than those without." Summary of Abstracts SESSION PO.ET03.02 – Drug Resistance in Molecular Targeted Therapies 2 April 16, 2023 – 1:30pm-5:00pm Abstract 427/22 – Newer generation mTOR inhibition represents effective therapeutic strategy for BRAF-mutant melanoma Gennie L Parkman, Tursun Turapov, David Kircher, William Burnett, Christopher Stehn, Kayla O'Toole, Katie Culver, Ashley Chadwick, Riley Elmer, Ryan Flaherty, Mona Foth, Karly Stanley, Robert Andtbacka, David Lum, Robert Judson-Torres, Martin McMahon, Sheri Holmen Huntsman Cancer Institute, University of Utah, Salt Lake City, UT University of Minnesota, Minneapolis, MN SESSION PO.CL09.01 – Combination Therapies for Cancer April 18, 2023 – 1:30pm-5:00pm Abstract 5490/8 – Combination of the PI3k inhibitor paxalisib with the nucleoside analog Gemcitabine over-activates the integrated stress response and induces atypical teratoid / rhabdoid tumor cell death Tyler Findlay, Kristen Malebranche, Anupa Geethadevi, Eric Raabe, Charles Eberhart, Jeffrey Rubens Johns Hopkins University School of Medicine, Baltimore, MD Abstract 5509/27 – The PI3K inhibitor paxalisib combines synergistically with the MEK inhibitor mirdametinib to target atypical teratoid / rhabdoid tumors Kristen J. Malebranche, Tyler Findlay, Anupa Geethadevi, Charles Eberhart, Eric Raabe, Jeffrey Rubens Johns Hopkins University School of Medicine, Baltimore, MD SESSION PO.ET01.04 – Targeting Protein Kinases and Phosphatases for Therapy 1 April 18, 2023 – 1:30pm-5:00pm Abstract 4990/3 – Dual inhibitor of ACVR1 and MEK 1/2 E6201 and PI3K/mTOR inhibitor paxalisib synergistically inhibit cell growth in DMG Hyuk Jean Kwon, Abigail Tindall, Charles Eberhart, Jeffrey Rubens, Eric Raabe Johns Hopkins University School of Medicine, Baltimore, MD SESSION PO.CL01.06 – Diagnostic and Prognostic Biomarkers 1 April 16, 2023 – 1:30pm-5:00pm Abstract 1015/25 – VEGFR-3 expression profiling by histology to classify patient population for the selective VEGFR-3 inhibitor EVT801 Michael Paillasse, Pierre-Benoit Ancey, Gaelle Badet, Anne Gomez-Brouchet, Janik Selves, Philippe Rochaix, Maxime Battistella, Celeste Lebbe, Philippe Cassier, Carlos Gomez-Roca, Jean-Pierre Delord, Mark Whittaker, Lise Davenne, John Friend, Michael Fitzgerald, James Garner, Pierre Fons Evotec SE, Toulouse, France & Abingdon, UK Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France, Université de Paris Cité, AP-HP Hôpital Saint Louis, Paris, France, Centre Léon Bérard, Lyon, France Kazia Therapeutics Ltd, Sydney, Australia About Kazia Therapeutics Limited Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA) is an oncology-focused drug development company, based in Sydney, Australia. Our lead program is paxalisib, a brain-penetrant inhibitor of the PI3K / Akt / mTOR pathway, which is being developed to treat multiple forms of brain cancer. Licensed from Genentech in late 2016, paxalisib is or has been the subject of ten clinical trials in this disease. A completed phase II study in glioblastoma reported promising signals of efficacy in 2021, and a pivotal study for registration, GBM AGILE, is ongoing, with final data expected in CY2023. Other clinical trials are ongoing in brain metastases, diffuse midline gliomas, and primary CNS lymphoma, with several of these having reported encouraging interim data. Paxalisib was granted Orphan Drug Designation for glioblastoma by the US FDA in February 2018, and Fast Track Designation for glioblastoma by the US FDA in August 2020. In addition, paxalisib was granted Rare Pediatric Disease Designation and Orphan Designation by the US FDA for DIPG in August 2020, and for atypical teratoid / rhabdoid tumours (AT/RT) in June 2022 and July 2022, respectively. Kazia is also developing EVT801, a small-molecule inhibitor of VEGFR3, which was licensed from Evotec SE in April 2021. Preclinical data has shown EVT801 to be active against a broad range of tumour types and has provided compelling evidence of synergy with immuno-oncology agents. A phase I study commenced recruitment in November 2021. For more information, please visit or follow us on Twitter @KaziaTx. This document was authorized for release to the ASX by James Garner, Chief Executive Officer, Managing Director. Forward-Looking Statements This announcement may contain forward-looking statements, which can generally be identified as such by the use of words such as "may," "will," "estimate," "future," "forward," "anticipate," or other similar words. Any statement describing Kazia's future plans, strategies, intentions, expectations, objectives, goals or prospects, and other statements that are not historical facts, are also forward-looking statements, including, but not limited to, statements regarding: the timing for results and data related to Kazia's clinical and preclinical trials, and Kazia's strategy and plans with respect to its programs, including paxalisib. Such statements are based on Kazia's expectations and projections about future events and future trends affecting its business and are subject to certain risks and uncertainties that could cause actual results to differ materially from those anticipated in the forward-looking statements, including risks and uncertainties: associated with clinical and preclinical trials and product development, related to regulatory approvals, and the related to the impact of global economic conditions. These and other risks and uncertainties are described more fully in Kazia's Annual Report, filed on form 20-F with the SEC, and in subsequent filings with the SEC. Kazia undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required under applicable law. You should not place undue reliance on these forward-looking statements, which apply only as of the date of this announcement. For More Information, Please Contact:- Jane Lowe IR Department jane.lowe@irdepartment.com.au Phone: +61 411 117 774 Company Codes: NASDAQ-SMALL:KZIA, Australia:KZA