Medulloblastoma

Total operating revenues for the full year 2023 were $16.3M, compared to $15.8M for the same period in 2022. As of March 7, 2024, Ryvu's cash position was $57.2M, excluding the first tranche of €8M in venture debt from the EIB, expected imminently. Together with other already secured funding sources, this cash position provides a runway through Q1 2026. Ryvu will present preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24) at the upcoming 2024 American Association for Cancer Research (AACR) Annual Meeting (April 5-10, San Diego, California). After announcing the hematology-focused RVU120 development plan in Q4 2023, Ryvu launched two Phase II studies in early 2024. An additional two Phase II clinical trials for RVU120 are expected to be launched in mid-2024. By the end of the year, the company plans to enroll over 100 patients across all RVU120 Phase II studies and aims to present initial Phase II data. KRAKOW, Poland, March 13, 2024 /PRNewswire/ -- Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small-molecule therapies that address emerging targets in oncology, summarizes its 2023 fiscal year and provides a corporate update. Pawel Przewiezlikowski, co-founder, largest shareholder, and Chief Executive Officer of Ryvu Therapeutics, said: - In 2023, we made significant progress in all key business areas and look forward to multiple catalysts in 2024. We have already started two Phase II studies of RVU120, and around mid-year, we plan to launch two more Phase II studies in hematology. By the end of the year, we plan to enroll more than 100 patients across these clinical trials. We also plan to launch a new Phase II study of MEN1703 (SEL24) in DLBCL, which is being developed under a license agreement with the Menarini Group. Study start-up activities for new trials of both RVU120 and MEN1703 are proceeding quickly. Krzysztof Brzozka, Ph.D., Executive Vice President, and Chief Scientific Officer, said: - We are pleased with the significant progress made in our early-phase projects. Among the most advanced projects from our synthetic lethality platform – PRMT5 and WRN – we plan to identify a clinical candidate in 2024. We are also seeing progress in the programs being developed by our partners – particularly BioNTech and Exelixis. We were excited to achieve the second milestone in the Exelixis collaboration, and we look forward to presenting data on our synthetic lethality assets and novel platform at AACR. 2023 SUMMARY AND RECENT CORPORATE EVENTS RVU120 clinical development plan In 2023 Ryvu prepared for the launch of two Phase II RVU120 trials, which then initiated in early 2024: 1) RVU120 as monotherapy in genetically defined cohorts of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS, RIVER-52 study), and 2) RVU120 in combination with venetoclax for patients with relapsed/ refractory AML (RIVER-81 study). Ryvu will financially support the REMARK study's Phase II clinical trial of RVU120 in patients with low-risk myelodysplastic syndromes (LR-MDS). REMARK will be conducted as an investigator-initiated study through the EMSCO network, with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator. Start-up activities have already been launched, and patient enrollment will start in mid-2024. Study start-up is also underway for POTAMI-61, a Phase II study evaluating the efficacy of RVU120 in patients with myelofibrosis (MF). Initiation of patient recruitment is scheduled for mid-2024. Translational research on RVU120 in solid tumors will continue, including combination studies, as well as academic collaborations in the areas of medulloblastoma (MB) and sarcoma-related research. The company plans to enroll more than 100 patients across all RVU120 Phase II trials this year and aims to present initial Phase II data by the end of 2024. RVU120's updated clinical development plan includes studies (RIVER-52, RIVER-81, and POTAMI-61) that could lead to three drug approvals between 2026 and 2027. Key data presented during 2023 conferences In 2023, Ryvu Therapeutics presented data from the RVU120 program at several international conferences, including EHA 2023, ESMO 2023, and ASH 2023: RVU120 monotherapy demonstrated clinical activity in a Phase Ib study in which 50% of evaluable patients with r/r AML or HR-MDS achieved clinical benefit, including a complete response, morphologically leukemia-free status, clinically significant reduction of blasts including reductions that allowed bridging to a bone marrow transplantation, two-year disease stabilization, hematologic improvements, as well as reduction in bone marrow fibrosis. In particular, early signs of efficacy were observed in patients with an NPM1 mutation, DNMT3a mutation, and HR-MDS. The recommended Phase II dose (RP2D) of 250 mg was found to be safe and well-tolerated, achieving RVU120 concentrations in the pharmacologically active range, with a level of target inhibition between 50% and 70%. This level of target inhibition is expected to result in therapeutic efficacy in selected patients or in combinations with synergistic therapies. RVU120 is emerging as a potential candidate in the first-line treatment of AML, supported by its activity against leukemic stem cells. RVU120 acts synergistically with venetoclax in both sensitive and venetoclax-resistant models. At the ENA conference in October 2023, Ryvu presented preclinical data for PRMT5 and the synthetic lethality platform, and Ryvu's partner – Menarini Group, presented preclinical data for MEN1703 in advanced diffuse large B-cell lymphoma (DLBCL). Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors with outstanding drug-like physicochemical properties and the ability to block methyltransferase activity of PRMT5 with nanomolar concentrations and bioavailable upon oral administration. The novel, optimized inhibitors exhibit a significantly improved pharmacokinetic profile. In addition, the compounds show antitumor efficacy and target engagement in vivo, providing a solid foundation for further development towards clinical trials. MEN1703 (SEL24) has shown promising antitumor activity in translational studies in various types of DLBCL. These data justify the development of MEN1703 in Phase II clinical trials in this indication. Expansion of MEN1703 (SEL24) development by Ryvu's partner – Menarini Group, to include a new Phase II clinical trial in DLBCL. In September 2023, Ryvu announced the Menarini Group's decision to expand the development of MEN1703 (SEL24) by initiating a new Phase II clinical trial in patients with DLBCL. A Phase II study in DLBCL is scheduled to begin in mid-2024. The goal is to evaluate the activity of MEN1703 (SEL24) as monotherapy and in combination with standard therapy in patients with DLBCL. The study will be initiated based on the potent activity of MEN1703 (SEL24) observed in preclinical lymphoma models. Clinical trials have confirmed the acceptable safety profile and early signs of activity of MEN1703 (SEL24) as a monotherapy. Based on the available data, further program development will continue in patients with DLBCL and potentially in additional indications. Recent financial events On February 3, 2024, Ryvu received notice that the second financial milestone was achieved under the collaboration agreement with Exelixis, resulting in a $2M payment to Ryvu. Ryvu and Exelixis are working under a research collaboration and license agreement to develop antibody-drug conjugates (ADCs) with Ryvu's portfolio of STING agonists. On March 5, 2024, Ryvu received notice from the European Investment Bank (EIB) that it had met the conditions for disbursement of the first venture debt tranche of €8M. These funds are not yet included in the cash balance reported in this press release, but Ryvu expects to receive the funds on March 13, 2024. As part of the agreement announced in August 2022, Ryvu still has access to an additional €14M in venture debt from the EIB. UPCOMING EVENTS Ryvu will attend the AACR Annual Meeting (San Diego, USA) from April 5-10, 2024, to present preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24). 2023 Fiscal Year Financial Update [1] Cash Position – On December 31, 2023, Ryvu Therapeutics held $63.7M in cash, cash equivalents, and bonds, compared to $23.2M at the end of 2022. On March 7, 2024, Ryvu Therapeutics held $57.2M in cash, cash equivalents, and bonds, which excludes €8M in venture debt from the EIB to be received imminently. Operating Revenues – In 2023, Ryvu recognized total operating revenues (including grants) of $16.3M, compared to 2022, when the total operating revenue amounted to $15.8M. Operating costs, excluding the non-cash cost of valuation of the Incentive Program ($2.0M) and valuation of NodThera shares ($0.9M) in the full year 2023, amounted to $37.6M, representing an increase compared to $26.4M in the previous year. Net Loss Attributable to Common Shareholders – In 2023, the net loss attributable to common shareholders, excluding the non-cash cost of valuation of the Incentive Program, amounted to $20.0M, compared to $13.8M in the previous year. About Ryvu Therapeutics Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel small-molecule therapies that address emerging targets in oncology. Internally discovered pipeline candidates use diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules directed at kinase, synthetic lethality, and immuno-oncology targets. Ryvu's most advanced programs include RVU120, a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies and solid tumors, currently in Phase II development (i) as a monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS) as well as (ii) in combination with venetoclax for the treatment of patients with r/r AML. Another clinical program, SEL24 (MEN1703), is a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group. Ryvu Therapeutics has signed multiple partnering and licensing deals with global companies, including BioNTech and Exelixis. The Company was founded in 2007 and is headquartered in Kraków, Poland. Ryvu is listed on the Warsaw Stock Exchange and is a component of the mWIG40 index. For more information, please see . [1] USD figures are provided at a conversion rate of: for the period from 01/01/2023 – 31/12/2023: PLN 4.1823; for the period from 01/01/2022 – 31/12/2022: PLN 4.4679; as of 7/03/2024: PLN 3.9485 as of 31/12/2023: PLN 3.9350 as of 31/12/2022: PLN 4.4018 SOURCE Ryvu Therapeutics

Targeting a non-encoding stretch of RNA may help shrink tumors caused by an aggressive type of brain cancer in children, according to new research in mice. Targeting a non-encoding stretch of RNA may help shrink tumors caused by an aggressive type of brain cancer in children, according to new research in mice reported March 8 in Cell Reports by Johns Hopkins Kimmel Cancer Center investigators. Medulloblastoma are the most common type of malignant brain cancer in children. The most aggressive and difficult-to-treat form of the disease is group 3 medulloblastoma, which is often fatal. By targeting long, noncoding genetic material called lnc-RNAs that drive the expression of cancer-causing genes, the study's senior author, Ranjan Perera, Ph.D., director of the Center for RNA Biology at Johns Hopkins All Children's Hospital in St. Petersburg, Florida, and his colleagues have demonstrated an innovative new approach that shrinks group 3 medulloblastoma tumors in mice. "Group 3 medulloblastoma is very aggressive, and there are currently no targeted therapies," says Perera, who has a primary affiliation in the Department of Neurosurgery, is a member of the Johns Hopkins Kimmel Cancer Center and is an associate professor of oncology at the Johns Hopkins University School of Medicine. He is also a senior scientist at the Johns Hopkins All Children's Hospital Cancer and Blood Disorders Institute, and has a secondary affiliation with the hospital's Institute for Fundamental Biomedical Research. "Our novel therapeutic approach based on noncoding RNA could fill an urgent need for new therapies for this devastating disease in children." RNA acts as a template for building proteins based on instructions encoded in the DNA. Until recently, scientists thought 97% of RNA was "junk" because only 3% is used to build proteins. However, scientists have realized that RNA's nonprotein encoding stretches control gene expression. A previous study by Perera and colleagues showed that a long noncoding stretch of RNA called lnc-HLX-2-7 contributes to the growth of group 3 medulloblastoma tumors by attaching to a DNA promoter that increases expression of cancer-causing genes. Promoters are nongene coding stretches of DNA adjacent to genes that act like switches turning them on. The new study provides additional details showing that lnc-HLX-2-7 specifically binds to the HLX promoter region of DNA, increasing HLX gene expression and causing the tumor to grow. HLX triggers tumor growth by binding to promoter regions for several other cancer-causing genes, increasing their expression. One gene that HLX increases expression of is MYC, which also increases the expression of several other cancer-causing genes, causing a cascade of activity that accelerates the growth of group 3 medulloblastoma tumors. Perera and his team developed an intravenous treatment to block lnc-HLX-2-7 from binding to the HLX promoter to stop this cascade of cancer-gene expression. They assembled a sequence of nucleotides (called antisense oligo nucleotides), the building blocks of RNA, that can bind to the corresponding nucleotides that make up lnc-HLX-2-7, preventing it from binding to the HLX promoter in the DNA and leading to its destruction. They coated the sequence with microscopic particles called cerium oxide nanoparticles to protect the lnc-HLX-2-7 until it reaches its target. When the team treated a mouse model of group 3 medulloblastoma with the experimental intravenous therapy, it reduced tumor growth by 40%-50%. Adding cisplatin, a chemotherapy drug currently used to treat medulloblastomas, alongside the new therapy caused the tumors to shrink even more and prolonged the animals' survival. The combination therapy extended the animals' lives by about 84 days compared with a 44-day increase in survival on lnc-HLX-2-7 alone. "When you combine the two treatments, you see dramatic effects," Perera says. Perera and his colleagues will collaborate with Johns Hopkins neurosurgeons to plan studies of the therapy in humans to further test its safety and efficacy. "Understanding why MYC is elevated in these tumors is extremely important, and this new link to HLX provides insights that open new therapeutic possibilities," says study co-author and Kimmel Cancer Center researcher Charles Eberhart, M.D., Ph.D., director of neuropathology and ophthalmic pathology and a professor of oncology and pathology at the Johns Hopkins University School of Medicine. The work was supported by the Schamroth Project, funded by Ian's Friends Foundation, the Hough Family Foundation, the National Institutes of Health (grant P30 CA006973), the National Cancer Institute (grants 5P30CA030199, R01NS124668-01A1, and R35NS122339), and a CPRIT Scholar award from the MD Anderson Cancer Center. Study co-authors were Keisuke Katsushima, Kandarp Joshi, Menglang Yuan, Stacie Stapleton and George Jallo from Johns Hopkins. Other authors were from the University of Delaware; the University of Central Florida, Orlando; Institute Curie at PSL University in Paris; Texas Children's Cancer Center, Houston; Baylor College of Medicine, Houston; and Columbia University Medical Center, New York.

Dr. Yael Mossé receives recognition for project dedicated to researching and potentially developing new therapies for undruggable solid tumors PHILADELPHIA, March 6, 2024 /PRNewswire/ -- An interdisciplinary, global team of scientists led by Yael Mossé, MD, Professor of Pediatrics in the Cancer Center at Children's Hospital of Philadelphia (CHOP), has been selected as one of five research teams from all over the world to receive funds from Cancer Grand Challenges, a funding initiative co-founded by the National Cancer Institute and Cancer Research UK. Mossé's international team will receive up to $25 million to develop transformative new therapies for previously undruggable forms of childhood cancer. Continue Reading International team led by Dr. Yael Mossé, Professor of Pediatrics in the Cancer Center at Children's Hospital of Philadelphia, will receive up to $25 million to develop transformative new therapies for previously undruggable forms of childhood cancer. Last year, 176 global teams submitted bold ideas for tackling some of the most pressing challenges in cancer research and care. Twelve teams were shortlisted, and the project "Developing a suite of oncoprotein degraders for childhood solid cancers," nicknamed Team KOODAC3, emerged as one of five teams to receive funding after a year-long rigorous selection process. The team unites the expertise of researchers from the United States, Austria, France, Germany and the United Kingdom to tackle the challenge of oncogene-addicted solid tumors in children. While survival rates for many childhood cancers have improved dramatically through the combination of standard chemotherapy and radiation therapy, survivors are often burdened with life threatening toxicities related to those therapies. Genetic discoveries related to cancer have transformed how many types of tumors are treated. Cancer is caused by genetic mutations that transform normal genes into oncogenes. These oncogenes are then translated into proteins that are not typically found in the cell, known as oncoproteins. Several drugs have been developed to treat different tumors by targeting oncogenes and their associated oncoproteins. Despite advances in this field, a critical challenge has been the difficulty of targeting proteins responsible for causing solid tumors related to childhood cancers. As a result, cure rates for most solid tumors have not improved at the rate of other types of cancer. KOODAC3 aims to develop drugs that break down or 'degrade' five of the most significant oncoproteins in children with high-risk oncogene-driven cancers, including neuroblastoma, medulloblastoma, Ewing sarcoma, fibrolamellar hepatocellular carcinoma, rhabdomyosarcoma and other cancers that deregulate these essential oncoproteins. The team is addressing this challenge by extending an ongoing collaboration with Nurix Therapeutics, a leading biopharmaceutical company focused on degrader drugs, providing a streamlined route for clinical translation of discoveries made by Team KOODAC3. Collectively, this consortium has the ambitious goal of developing oral drugs that will be deployed world-wide in partnership with a robust international patient advocacy committee that will inform outreach to childhood cancer communities globally. "Our team is deeply honored to have been selected as one of the five to receive funding from the Cancer Grand Challenges initiative," said Mossé. "Team KOODAC3 was brought together with the goal of identifying new strategies for treating high-risk pediatric cancers with a high unmet need. Each of the projects that applied for this funding were worthy, so we do not take this award lightly and we are committed to bringing our expertise together with the goal of developing paradigm-altering safe and effective new therapies for currently lethal childhood solid cancers." Additional CHOP co-investigators who are part of Team KOODAC3 include John Maris, MD, and Adam Wolpaw, MD, PhD. "At CHOP, our researchers are committed to creating life-changing solutions for children around the world, and improving the care for some of the most difficult to treat childhood cancers is what drives so much of what we do," said Susan L. Furth, MD, PhD, Executive Vice President and Chief Scientific Officer at CHOP. "We are thrilled that this prestigious organization recognized the importance of what this project is trying to achieve, and we expect the funding to help us make important strides toward our understanding of childhood cancer." The National Cancer Institute and Cancer Research UK, the world's leading funders of cancer research, co-founded and launched the Cancer Grand Challenges initiative in 2020. Cancer Grand Challenges aims to provide funding for interdisciplinary research teams from around the world whose novel ideas offer the greatest potential to advance bold cancer research and improve outcomes for people affected by cancer. The team is co-led by Martin Eilers at the University of Würzburg in Germany and is funded by Cancer Research UK, Institut National Du Cancer and KiKa (Children Cancer Free Foundation) through Cancer Grand Challenges. Learn more about the Cancer Grand Challenges at . In addition to the Team KOODAC3 award, Team MATCHMAKERS, which includes Dr. Nikolaos G. Sgourakis from CHOP, also received a Cancer Grand Challenges award of up to $25 million. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Jennifer Lee Children's Hospital of Philadelphia (610)800-6592 [email protected] SOURCE Children's Hospital of Philadelphia