Pancreatic adenocarcinoma

March 05, 2024 (GLOBE NEWSWIRE) -- Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, announced today that it will be presenting preclinical data on its lead program IMM-1-104 at the American Association for Cancer Research (AACR) annual meeting, held April 5-10 in San Diego, California. Details for the poster presentation are as follows: Title: Activity of IMM-1-104 alone or in combination with chemotherapy in RAS-altered pancreatic cancer models Date and Time: Tuesday Apr 9, 2024, 9:00 AM - 12:30 PM PT Poster Session: In Vivo Imaging and Humanized Models Location: Poster Section 9, Poster Board #19 Abstract Number: 4195 The abstract is available on the AACR Online Program and will be published in the online Proceedings of the AACR. Following presentation, the poster will be available on the publications section of Immuneering’s website. Immuneering is a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients with an initial aim to develop a universal-RAS therapy. The Company aims to achieve universal activity through deep cyclic inhibition of the MAPK pathway, impacting cancer cells while sparing healthy cells. Immuneering’s lead product candidate, IMM-1-104, is an oral, once-daily deep cyclic inhibitor currently in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations. IMM-6-415 is an oral, twice-daily deep cyclic inhibitor and will be evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS or RAF mutations. The company’s development pipeline also includes several early-stage programs. For more information, please visit www.immuneering.com. The content above comes from the network. if any infringement, please contact us to modify.

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) (“Merrimack” or the “Company”) today announced its full year 2023 financial results for the period ended December 31, 2023. “As Ipsen reported in February, the U.S. Food and Drug Administration has approved the supplemental new drug application for Onivyde® (irinotecan liposome injection) plus 5 fluorouracil/leucovorin and oxaliplatin (NALIRIFOX) as a first-line treatment for people living with metastatic pancreatic ductal adenocarcinoma (mPDAC),” said Gary Crocker, CEO and Chairman of Merrimack’s Board of Directors. “This approval triggers a $225 million payment which is due from Ipsen to Merrimack before the end of March. We expect to hold a special meeting of stockholders to approve a Plan of Dissolution and a liquidating dividend payable to stockholders. We currently anticipate the initial liquidating dividend to be in the range of between approximately $14.65 and $15.35 per share.” Full Year 2023 Financial Results Merrimack reported net loss of $1.2 million for the year ended December 31, 2023, or $0.08 per basic share, compared to a net loss of $1.5 million, or $0.11 per basic share, for the same period in 2022. Merrimack reported a gain on sale of assets for the year ended December 31, 2023, of $0.1 million compared to $0.4 million for the same period in 2022. General and administrative expenses for the year ended December 31, 2023 were $2.2 million, compared to $2.2 million for the same period in 2022. As of December 31, 2023, Merrimack had cash, cash equivalents and short-term investments of $18.9 million, compared to $19.4 million as of December 31, 2022. As of December 31, 2023, Merrimack had 14.4 million shares of common stock outstanding. Updates on Programs Underlying Potential Milestone Payments and Planned Dissolution On February 13, 2024, we announced that Ipsen S.A. announced it had received approval from the U.S. Food and Drug Administration, or FDA, to market ONIVYDE as a first-line treatment of metastatic adenocarcinoma on the pancreas. As a result of this approval by the FDA, we are entitled to receive a $225 million milestone payment from Ipsen, which is expected to be received by the end of March 2024. Merrimack’s Board of Directors has evaluated the likelihood of receiving additional milestone payments under the Ipsen Agreement and from the 2019 Agreement with Elevation Oncology and has concluded that it is unlikely that any additional milestone payments from either agreement will become payable. The Plan of Dissolution will include establishment of a liquidating trust for the benefit of stockholders in the unlikely event that Merrimack might receive any future milestone payments from Ipsen or Elevation Technology. About Merrimack Merrimack Pharmaceuticals, Inc. is a biopharmaceutical company based in Cambridge, Massachusetts that is entitled to receive up to $450.0 million in contingent milestone payments related to its sale of Onivyde® to Ipsen S.A. in April 2017. $225 million of these potential milestone payments are tied to the first line metastatic pancreatic ductal adenocarcinoma potential indication and are expected to be received by the end of March. The remaining milestone payments consist of $150 million tied to the small cell lung cancer potential indication and $75 million is tied to other potential applications Ipsen may elect to pursue. These milestone payments would be payable by Ipsen upon approval by the U.S. Food and Drug Administration (“FDA”) of Onivyde for certain additional clinical indications. Merrimack’s agreement with Ipsen does not require Ipsen to provide Merrimack with any information on the progress of Onivyde clinical trials that is not publicly available. Merrimack is also entitled to receive up to $54.5 million in contingent milestone payments related to its sale of anti-HER3 programs to Elevation Oncology (formerly 14ner Oncology, Inc.) in July 2019. Forward Looking Statements To the extent that statements contained in this press release are not descriptions of historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include any statements about Merrimack’s strategy, future operations, future financial position, future revenues and future expectations and plans and prospects for Merrimack, and any other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue” and similar expressions. In this press release, Merrimack’s forward-looking statements include, among others, Merrimack’s rights to receive payments related to certain milestone events or whether such milestones will be achieved, if at all, the sufficiency of Merrimack’s cash resources and Merrimack’s strategic plan, including any potential distribution of additional cash to Merrimack’s shareholders. Such forward-looking statements involve substantial risks and uncertainties that could cause Merrimack’s future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others: (i) receiving the $225 million milestone payment from Ipsen which Ipsen is contractually obligated to pay based on receipt of the FDA approval for the supplemental new drug application for Onivyde (irinotecan liposome injection) plus 5 fluorouracil/leucovorin and oxaliplatin (NALIRIFOX), (ii) positive information about pre-clinical and early stage clinical trial results does not ensure that later stage or larger scale clinical trials will be successful (for example, Onivyde® may not demonstrate promising therapeutic effect or appropriate safety profiles in current or later stage or larger scale clinical trials as a result of known or as yet unanticipated side effects, (iii) the results achieved in later stage trials may not be sufficient to meet applicable regulatory standards or to justify further development; (iv) problems or delays may arise prior to the initiation of planned clinical trials, during clinical trials or in the course of developing, testing or manufacturing that could lead Ipsen and Elevation Oncology and their partners and collaborators to fail to initiate or to discontinue development; (v) even if later stage clinical trials are successful, unexpected concerns may arise from subsequent analysis of data or from additional data; (vi) obstacles may arise or issues may be identified in connection with review of clinical data with regulatory authorities; (vii) regulatory authorities may disagree with Ipsen and Elevation Oncology’s view of the data or require additional data or information or additional studies, (viii) in addition, the planned timing of initiation and completion of clinical trials based upon Onivyde and the anti-HER Program are subject to the ability of each of Ipsen and Elevation Oncology, respectively, to enroll patients, enter into agreements with clinical trial sites and investigators, and overcome technical hurdles and other issues related to the conduct of the trials for which each of them is responsible and, with regard to Elevation Technology, access to adequate capital to conduct such trials; (ix) each of Ipsen and Elevation Oncology are subject to the risk that they may not successfully commercialize these development programs; (x) Merrimack is also subject to the risk that it may not have funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements; (xi) press releases and other public statements by Ipsen and Elevation Oncology may contain forward-looking statements which may later prove to be inaccurate. Merrimack undertakes no obligation to update or revise any forward-looking statements. Forward-looking statements should not be relied upon as representing Merrimack’s views as of any date subsequent to the date hereof. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Merrimack’s business in general, see the “Risk Factors” section of Merrimack’s Annual Report on Form 10-K filed with the SEC on March 9, 2023, any subsequent quarterly report on Form 10-Q filed by Merrimack and the other reports Merrimack files with the Securities and Exchange Commission. View source version on businesswire.com: Contacts Tim Surgenor ir@merrimack.com Source: Merrimack Pharmaceuticals, Inc. View this news release online at:

Updated preclinical data will be presented from Ryvu's synthetic lethality pipeline, including PRMT5 inhibitors in MTAP-Deficient cancers, WRN inhibitors for the treatment of microsatellite unstable (MSI-H) tumors, and Ryvu's cutting-edge synthetic lethality platform based on primary cancer cells. Poster presentation to highlight the synergistic effects of RVU120 in combination with ruxolitinib in myeloproliferative neoplasms. Ryvu's partner Menarini to present data on MEN1703 (SEL24), demonstrating promising anti-tumor activity in preclinical models of myelofibrosis both as a single agent and combined with ruxolitinib. KRAKOW, Poland, March 6, 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, announced today that preclinical data from its synthetic lethality pipeline and RVU120 project, as well as on MEN1703 (SEL24), will be presented at the upcoming 2024 AACR Annual Meeting, scheduled for April 5-10 in San Diego, California. "We are excited to present our latest preclinical data at the AACR Annual Meeting, showcasing our significant progress in advancing novel small molecule therapies for oncology. This year, we will present data from our most advanced preclinical project on MTA-cooperative PRMT5 inhibitors, the lead program within Ryvu's synthetic lethality pipeline. Our PRMT5 inhibitors have demonstrated remarkable efficacy and selectivity in preclinical models of tumors with MTAP gene deletion, providing a strong foundation for further development," said Krzysztof Brzózka, Ph.D., Chief Scientific Officer of Ryvu Therapeutics. "Our discovery platform continues to produce novel precision medicine targets and drugs, and we are proud to highlight platform data based on primary cancer cells, specifically in colorectal cancer models with broader applicability across cancers. " Details on the poster presentations are as follows: Abstract Title: "Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers." Session Name: HDAC and Methyltransferase Inhibitors Session date and time: Tuesday, April 9, 9:00 AM - 12:30 PM EST Poster Number: 4598 Co-deletion of MTAP is observed in approximately 80-90% of tumors with homozygous deletion of CDKN2A, representing 10-15% of all human tumors. These tumor types, including non-small cell lung cancer, pancreatic adenocarcinoma, glioblastoma, and mesothelioma, have a poor prognosis, highlighting the significant unmet medical need in this area. Deletion of MTAP leads to a significant accumulation of methylthioadenosine (MTA) in cells. MTA, at high concentrations, selectively inhibits the PRMT5 methyltransferase enzyme. As a result, the overall level of symmetric arginine dimethylation throughout the proteome is reduced, which makes cells with MTAP deletion more susceptible to therapeutic targeting of PRMT5. Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors showing favorable drug-like properties and effective PRMT5 inhibition dependent on MTA binding. Structure-based lead optimization has enabled rapid expansion and delivery of two independent chemical series with novel intellectual property, characterized by high target engagement in cells, and selective potency in MTAP-deleted cell lines, along with favorable DMPK profiles allowing an oral administration. The antitumor activities were compared in vitro and in vivo in MTAP null tumors. The correlation between compound exposure and on-target effect was confirmed in PK/PD and efficacy studies. Performed studies confirm that MTA-cooperative PRMT5 inhibitors exert a strong synthetic lethal phenotype in MTAP-deleted cancers, offering an exciting therapeutic opportunity for a large patient population. Abstract Title: "A comprehensive platform for identification of KRAS-specific synthetic lethal targets using patient-derived cells." Session Name: New Targets, Technologies, and Drug Delivery Systems Session date and time: Tuesday, April 9, 9:00 AM - 12:30 PM EST Poster Number: 4684 Ryvu's cutting-edge drug discovery platform uniquely combines high throughput capabilities with the precision and translational impact traditionally associated with later, lower throughput stages. Our approach taps into the power of primary cells to transform cancer treatment, focusing especially on colorectal cancer (CRC). By leveraging human stem cell derived model cells (PDC), patient-derived xenografts (PDXs) and clinical samples we have created a groundbreaking approach to identify synthetic lethal (SL) targets specific to oncogenic pathways. We integrate CRISPR/Cas9 technology, phenotypic screening, RNA-seq, and whole-exome sequencing (WES), enabling rapid identification of molecular vulnerabilities. We present results obtained in engineered intestinal primary models which represent frequently altered genes in CRC, including KRAS G12D mutation. Notably, our use of normal hISCs facilitates the identification of genes essential only for transformed cells, amplifying the precision tumor targeting of our novel discoveries. Beyond CRC, our platform could extend to personalized medicine approaches in various cancer types. By spearheading the identification of KRAS-specific SL inhibitors, we pave the way for novel, targeted therapies, offering hope to patients battling this heterogeneous malignancy and beyond. Abstract Title: "Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors." Session Name: Novel Antitumor Agents 4 Session date and time: Tuesday, April 9, 1:30 PM – 05:00 PM EST Poster Number: 5942 The synthetic lethality resulting from the inhibition of the WRN helicase protein has been observed in tumors characterized by high levels of microsatellite instability (MSI-H). This instability stems from a deficiency in the DNA mismatch repair (MMR) mechanisms, leading to the accumulation of DNA damage. This phenomenon is notably prevalent in 10-30% of colorectal, gastric, endometrial, and ovarian cancers. Structure-based optimization performed at Ryvu facilitated the rapid expansion and delivery of a compound library with novel intellectual property (IP), demonstrating target engagement in cells and selective potency over other RecQ family members. The pharmacokinetic properties of these compounds were favorable and allowed progressing to in vivo studies which confirmed efficacy of our compounds in xenograft MSI-H cancer models. These data provide pharmacological proof-of-concept for the synthetic lethal effect of our inhibitors and support WRN inhibition as a new, targeted oncological therapy. Abstract Title: "Combination JAK1/2 and CDK8/19 inhibition demonstrates enhanced efficacy in myeloproliferative neoplasms." Session Name: Targeted, Combination, and Differentiation Therapies Session date and time: Wednesday, April 10, 9:00 AM - 12:30 PM EST Poster Number: 7225 The presentation, prepared in collaboration with Prof. Raajit Rampal's group from Memorial Sloan Kettering Cancer Center, includes the assessment of RVU120, a highly selective and potent CDK8/19 inhibitor, both in monotherapy and combination with ruxolitinib (RUX), a JAK1/2 inhibitor, for the treatment of myeloproliferative neoplasms (MPN) and hydroxyurea-resistant/intolerant polycythemia vera (PV). The combination of RVU120 and RUX demonstrated biochemical synergy and differential inhibition of STAT5 phosphorylation in vitro. Further, in vivo treatment with RVU120/RUX+RVU120 resulted in significant reductions in disease manifestation (splenomegaly, WBC, fibrosis scoring, hematopoiesis) compared to VEH/RUX. These data suggest that JAK1/2 and CDK8/19 inhibition could be a potential novel therapeutic strategy in MPNs. Additional work on nascent RNA expression and cytokine profiles aims at elucidating the exact mechanism of synergy between tested compounds. Abstract Title: "MEN1703/SEL24 exhibits promising antitumoral activity in preclinical models of myelofibrosis both as single agent and combined with ruxolitinib." Session Name: Novel Antitumor Agents 2 Session date and time: Sunday April 7, 01:30 AM – 0500 PM EST Poster Number: 665 MEN1703 (SEL24) is an oral, first-in-class, dual PIM/FLT3 kinase inhibitor in development for hematologic malignancies. The presented study aims to investigate the efficacy of MEN1703 alone and in combination with the JAK inhibitor ruxolitinib (RUX) in preclinical models of myelofibrosis (MF) and to elucidate the underlying signaling pathways. MEN1703 demonstrated anti-tumoral efficacy in MF preclinical models, exhibiting in vitro activity at clinically relevant concentrations. Importantly, the combination of MEN1703 with the standard of care, RUX, exhibited synergistic effects, and molecular analyses confirmed the inhibition of downstream targets of PIM. The results support the therapeutic potential and relevance of MEN1703 in the treatment strategies for myelofibrosis. All abstracts are now available online and can be obtained from the conference site: 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 . SOURCE Ryvu Therapeutics