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The roles and mechanisms of the m6A reader protein YTHDF1 in tumor biologyHepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. The development of HCC is influenced by both viral and non-viral factors. Non-alcoholic steatohepatitis (NASH) has emerged as a growing risk factor for HCC, as the prevalence of diabetes and metabolic syndrome increases. NASH is a progressive liver disease characterized by the accumulation of excessive triglycerides and is not caused by alcohol consumption. Although NASH is linked to the development of HCC, the molecular mechanisms underlying these diseases are not fully understood, which has hindered the development of effective treatments. Handicapping anti-PD1 therapyCurrently, there are no approved drugs or biological therapies specifically targeting NASH-related HCC (NASH-HCC). This deadly disease urgently requires new treatment methods. Immune checkpoint blockade (ICB) using monoclonal antibodies that target programmed cell death protein-1 (PD-1), programmed cell death-ligand 1 (PD-L1), or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has recently become a treatment option for HCC.  However, NASH-HCC's poor response to ICB treatment is due to NASH-related immune changes in the liver. Therefore, identifying potential therapeutic targets is critical to overcoming resistance to ICB treatment in NASH-HCC. YTHDF1, a m6A reader, is upregulated in human NASH-HCC tumors compared to peri-tumor tissues.N6-methyladenosine (m6A) is the most prevalent chemical modification in eukaryotic mRNA and is known to play a crucial role in post-transcriptional regulation. m6A modification regulates RNA fate by controlling RNA stability, processing, transport, localization, translation, and RNA-protein interactions. YTH domain-containing family protein 1 (YTHDF1) is a translation-promoting m6A reader that targets mRNAs in the cytoplasm and contributes to tumor progression by regulating cell proliferation, DNA damage, and immunity.  YTHDF1 deficiency in mice enhances antigen-specific CD8+ T cell-mediated anti-tumor responses in colorectal and gastric cancers, making it a potential therapeutic target for cancer immunotherapy. However, the role of YTHDF1 in the pathogenesis of HCC, particularly NASH-HCC, and its regulation of the tumor immune microenvironment are currently not well understood. A recent study published in Journal of Hepatology provides valuable insights into YTHDF1’s role in the progression of NASH-HCC. It is the first to demonstrate that tumor-intrinsic YTHDF1 is linked to the accumulation of myeloid-derived suppressor cells (MDSCs) in the NASH-HCC microenvironment. In transgenic mice with liver-specific YTHDF1 overexpression, YTHDF1 induces MDSC infiltration and accelerates spontaneous NASH-HCC.  Ythdf1 recruits MDSCs via IL-6 in NASH-HCC.The signaling cascade of YTHDF1 activates the EZH2-IL-6 signaling pathway to recruit MDSCs, resulting in T cell dysfunction and promoting tumor growth. Conversely, targeting YTHDF1 with lipid nanoparticle (LNP)-siRNA can significantly enhance the anti-PD-1 blockade effect in NASH-HCC mouse models, suggesting that YTHDF1 is a new target for enhancing the efficacy of immune checkpoint blockade therapy in NASH-HCC.  Targeting the accomplice: YTHDF1 According to the Synapse database, there are currently four patent applications targeting YTHDF1 for cancer therapy. Three of these applications are for the novel use of already existing drugs, while one is for a new formula: This is not the first time YTHDF1's role in cancer pathology has been elucidated. Last year, a study reported that YTHDF1 promotes breast cancer cell growth in both in vitro and in vivo environments and plays a crucial role in DNA damage repair and chemoresistance. And it seems that YTHDF1 modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner. METTL14 is involved in DNA replication, DNA damage repair and chemoresistance.On the other hand, YTHDF1 knockdown has been shown to sensitize breast cancer cells to Adriamycin and Cisplatin, as well as Olaparib, a PARP inhibitor. During the experiments, researchers observed that the knockdown of YTHDF1 in MDA-MB-231 cells resulted in a reduction of S-phase fraction and an increased G1-phase fraction. The YTHDF1 knockdown also downregulated CDK2 and Cyclin E2, while upregulating P21, a CDK inhibitor involved in S-phase.   YTHDF1’s roles in other types of cancer have been revealed as well. A study published earlier this year has suggested that YTHDF1 may play an important role in shaping the immune microenvironment of colorectal cancer (CRC).  In their study, the team of researchers revealed that removing YTHDF1 from mouse CRC cells (both microsatellite stable (MSS) and microsatellite instable-high (MSI-H) varieties) results in an accumulation of myeloid-derived suppressor cells (MDSCs). This accumulation subsequently inhibits the infiltration of T cells in both mouse CRC models and humanized mouse models, demonstrating a deep interconnectedness. The investigation led to the identification of p65/Rela as a target of YTHDF1. The researchers observed that YTHDF1 encouraged the production of p65 protein, which in turn escalated the regulation of CXCL1. This process amplified the migration of MDSCs through the CXCL1-CXCR2 pathway, resulting in an increased number of MDSCs. These MDSCs then countered the function of CD8+ T cells within the tumor immune microenvironment (TIME). This intricate research, along with the others discussed here, suggest that the strategic targeting of YTHDF1, potentially using techniques such as CRISPR or VNPs-siYTHDF1, could enhance the efficacy of anti-PD1 therapy in a variety of cancers. References: 1.Wang L. et al., Targeting N6-methyladenosine reader YTHDF1 with siRNA boosts anti-tumor immunity in NASH-HCC by inhibiting EZH2-IL-6 axis 2, Journal of Hepatology, Available online 17 July 2023. 2.Sun, Y., Dong, D., Xia, Y. et al. YTHDF1 promotes breast cancer cell growth, DNA damage repair and chemoresistance. Cell Death Dis 13, 230 (2022). 3.Bao Y, Zhai J, Chen H, et al, Targeting m6A reader YTHDF1 augments antitumour immunity and boosts anti-PD-1 efficacy in colorectal cancer, Gut 2023;72:1497-1509. 

SAN DIEGO, May 11, 2023 /PRNewswire/ -- Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, today announced financial results for its fiscal third quarter ended March 31, 2023 and provided a corporate update. RECENT CORPORATE DEVELOPMENTS Case study data from two abstracts was presented by MD Anderson Cancer Center from the VAL-083 expanded access program at the American Association for Cancer Research (AACR) Annual Meeting (April): RELA fusion-positive ependymoma and diffuse midline glioma treated with VAL-083 under expanded access - case reports. The abstract described two patient case reports, one with ependymoma and one with diffuse midline glioma, treated with VAL-083 under an expanded access program. The cases highlighted that VAL-083 may be a treatment option for recurrent RELA fusion-positive ependymoma and diffuse midline glioma refractory to other treatments. VAL-083 in patients with recurrent glioblastoma treated under expanded access program. The abstract reported on background characteristics, and safety and efficacy measures, from 24 patients with recurrent GBM treated with VAL-083 under an expanded access program. The posters illustrated that the use of VAL-083 continued to show benefit in the treatment of GBM patients who had multiple recurrences and have limited therapeutic options. "We are encouraged by the recent progress of our lead asset in brain cancer, VAL-083, including data presented at the AACR Annual Meeting, and look forward to announcing top-line data in the international registrational GBM AGILE Study before the end of calendar 2023," commented Robert E. Hoffman, Kintara's President and Chief Executive Officer. "We continue to be optimistic about the future of our REM-001 program for treating cutaneous metastatic breast cancer and our team is more committed than ever to bringing this innovative therapy to patients in need." SUMMARY OF FINANCIAL RESULTS FOR FISCAL YEAR 2023 THIRD QUARTER ENDED MARCH 31, 2023 As of March 31, 2023, Kintara had cash and cash equivalents of approximately $3.0 million. For the three months ended March 31, 2023, Kintara reported a net loss of approximately $3.3 million, or $1.94 per share, compared to a net loss of approximately $5.4 million, or $5.45 per share, for the three months ended March 31, 2022. For the nine months ended March 31, 2023, Kintara reported a net loss of approximately $11.3 million, or $7.32 per share, compared to a net loss of approximately $17.2 million, or $22.39 per share, for the nine months ended March 31, 2022. The decreased net losses for the three and nine months ended March 31, 2023 compared to the three and nine months ended March 31, 2022 was largely due to lower research and development expenses as well as lower general and administrative costs. Kintara's financial statements as filed with the U.S. Securities Exchange Commission can be viewed on the Company's website at: . ABOUT KINTARA Located in San Diego, California, Kintara is dedicated to the development of novel cancer therapies for patients with unmet medical needs. Kintara is developing two late-stage therapeutics for clear unmet medical needs with reduced risk development programs. The two programs are VAL-083 for glioblastoma (GBM) and REM-001 Therapy for cutaneous metastatic breast cancer (CMBC). VAL-083 is a 'first-in-class', small-molecule chemotherapeutic with a novel mechanism of action that has demonstrated clinical activity against a range of cancers, including central nervous system, ovarian and other solid tumors (e.g., NSCLC, bladder cancer, head and neck) in U.S. clinical trials sponsored by the National Cancer Institute (NCI). Based on Kintara's internal research programs and these prior NCI-sponsored clinical studies, Kintara is currently advancing VAL-083 in the Global Coalition for Adaptive Research registrational Phase 2/3 clinical trial titled Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) Study to support the development and commercialization of VAL-083 in GBM. Kintara also has a proprietary, late-stage photodynamic therapy platform that holds promise as a localized cutaneous, or visceral, tumor treatment as well as in other potential indications. REM-001 Therapy, which consists of the laser light source, the light delivery device, and the REM-001 drug product, has been previously studied in four Phase 2/3 clinical trials in patients with CMBC who had previously received chemotherapy and/or failed radiation therapy. In CMBC, REM-001 has a clinical efficacy to date of 80% complete responses of CMBC evaluable lesions and an existing robust safety database of approximately 1,100 patients across multiple indications. Kintara has paused the REM-001 CMBC program to conserve cash resources. For more information, please visit or follow us on Twitter at @Kintara_Thera, Facebook and Linkedin. SAFE HARBOR STATEMENT Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including statements regarding the status of the Company's clinical trials and the GBM AGILE Study. Any forward-looking statements contained herein are based on current expectations but are subject to a number of risks and uncertainties. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the Company's ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the Company's products and technology; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; the Company's business, research, product development, regulatory approval, marketing and distribution plans and strategies; global unrest; and the continued impact of the COVID-19 pandemic. These and other factors are identified and described in more detail in the Company's filings with the SEC, including the Company's Annual Report on Form 10-K for the year ended June 30, 2022, the Company's Quarterly Reports on Form 10-Q, and the Company's Current Reports on Form 8-K. CONTACTS Investors LifeSci Advisors Mike Moyer, Managing Director 617.308.4306 mmoyer@lifesciadvisors.com Media Inquiries David Schull or Ignacio Guerrero-Ros, Ph.D. Russo Partners 858.717.2310 646.942.5604 david.schull@russopartnersllc.com ignacio.guerrero-ros@russopartnersllc.com Company Codes: NASDAQ-NMS:KTRA

SAN DIEGO, April 14, 2023 /PRNewswire/ -- Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, today announced its participation in the upcoming 2023 American Association for Cancer Research (AACR) Annual Meeting, taking place in Orlando, Florida from April 14 through April 19, 2023, where VAL-083 data will be presented. Data Presentations: Session Title: Late-Breaking Research: Clinical Research 1 / Endocrinology Poster Section 34, Presentation Time: Monday, April 17, 2023 - 1:30 to 5:00 p.m. ET Abstract LB126: RELA fusion-positive ependymoma and diffuse midline glioma treated with VAL-083 under expanded access - case reports The abstract describes two patient case reports, one with ependymoma and one with diffuse midline glioma, treated with VAL-083 under an expanded access program. The cases highlight that VAL-083 may be a treatment option for recurrent RELA fusion-positive ependymoma and diffuse midline glioma refractory to other treatments. Safety and efficacy data will be updated at the poster presentation at the meeting. Abstract LB127: VAL-083 in patients with recurrent glioblastoma treated under expanded access program The abstract reports on background characteristics, and safety and efficacy measures, from 24 patients with recurrent GBM treated with VAL-083 under an expanded access program. Use of VAL-083 continues to show benefit in the treatment of GBM patients who have had multiple recurrences and have limited therapeutic options. This information will be updated in the poster presentation at the meeting. ABOUT KINTARA Located in San Diego, California, Kintara is dedicated to the development of novel cancer therapies for patients with unmet medical needs. Kintara is developing two late-stage therapeutics for clear unmet medical needs with reduced risk development programs. The two programs are VAL-083 for glioblastoma (GBM) and REM-001 Therapy for cutaneous metastatic breast cancer (CMBC). VAL-083 is a 'first-in-class', small-molecule chemotherapeutic with a novel mechanism of action that has demonstrated clinical activity against a range of cancers, including central nervous system, ovarian and other solid tumors (e.g., NSCLC, bladder cancer, head and neck) in U.S. clinical trials sponsored by the National Cancer Institute (NCI). Based on Kintara's internal research programs and these prior NCI-sponsored clinical studies, Kintara is currently advancing VAL-083 in the Global Coalition for Adaptive Research registrational Phase 2/3 clinical trial titled Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) Study to support the development and commercialization of VAL-083 in GBM. Kintara also has a proprietary, late-stage photodynamic therapy platform that holds promise as a localized cutaneous, or visceral, tumor treatment as well as in other potential indications. REM-001 Therapy, which consists of the laser light source, the light delivery device, and the REM-001 drug product, has been previously studied in four Phase 2/3 clinical trials in patients with CMBC who had previously received chemotherapy and/or failed radiation therapy. In CMBC, REM-001 has a clinical efficacy to date of 80% complete responses of CMBC evaluable lesions and an existing robust safety database of approximately 1,100 patients across multiple indications. Kintara has paused the REM-001 CMBC program to conserve cash resources. For more information, please visit or follow us on Twitter at @Kintara_Thera, Facebook and LinkedIn. SAFE HARBOR STATEMENT Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including statements regarding the status of the Company's clinical trials and the GBM AGILE Study. Any forward-looking statements contained herein are based on current expectations but are subject to a number of risks and uncertainties. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the Company's ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the Company's products and technology; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; the Company's business, research, product development, regulatory approval, marketing and distribution plans and strategies; global unrest; and the continued impact of the COVID-19 pandemic. These and other factors are identified and described in more detail in the Company's filings with the SEC, including the Company's Annual Report on Form 10-K for the year ended June 30, 2022, the Company's Quarterly Reports on Form 10-Q, and the Company's Current Reports on Form 8-K. CONTACTS Investors LifeSci Advisors Mike Moyer, Managing Director 617.308.4306 [email protected] Media Inquiries David Schull or Ignacio Guerrero-Ros, Ph.D. Russo Partners 858.717.2310 646.942.5604 [email protected] [email protected] SOURCE Kintara Therapeutics