Anophthalmia With Pulmonary Hypoplasia

BOSTON, Nov. 09, 2022 (GLOBE NEWSWIRE) -- TransCode Therapeutics, Inc. (Nasdaq: RNAZ), an RNA oncology company committed to more effectively treating cancer using RNA therapeutics, today reported positive preclinical results with its immunotherapy candidate, TTX-siPDL1, in pancreatic adenocarcinoma. After two weekly treatments with TTX-siPDL1 combined with the standard-of-care chemotherapeutic, gemcitabine, tumor volumes were 25% of those in untreated animals. By the fifth week of treatment, 75% of animals treated with TTX-siPDL1 plus gemcitabine were still alive versus 25% of those that were treated with gemcitabine alone. This is the second drug candidate from TransCode’s platform to show positive preclinical results in pancreatic cancer. The animal model used in this latest study involving TransCode’s siRNA immunotherapy candidate involved implantation of a highly aggressive murine cell line directly into the pancreata of recipient mice. Body weight and histopathology assessments provided preliminary evidence that the treatment was tolerated. Finally, immune cell profiling of tumors from the treated animals indicated successful PD-L1 inhibition and immune cell activation, consistent with the known mechanism-of-action (MOA) of checkpoint inhibitors. Because TTX-siPDL1 incorporates a siRNA against PD-L1 as its functional component, it has the potential to trigger the degradation and/or translational repression of the PD-L1 messenger RNA (mRNA), preventing the cell from expressing the PD-L1 antigen. Pancreatic cancer has proven difficult to treat with conventional drugs and has been resistant to initial immunotherapy approaches. The reason pancreatic cancer is challenging to treat with immunotherapy is in part due to the presence of a thick fibrous corona surrounding the tumor. In human pancreatic ductal adenocarcinoma, or PDAC, up to 90% of the total volume of the tumor is represented by fibrous tissue, inhibiting access of therapeutics and immune cells into the tumor. “This is yet another opportunity to showcase our TTX platform which is designed to overcome challenges faced by existing lipid and liposomal systems in delivering RNA therapeutics inside tumor cells and metastatic sites. Demonstrating the ability to deliver RNA therapeutics inside tumors and metastases and to affect documented targets for cancer treatment that have remained undruggable until now using an RNA approach represents a major opportunity for our company,” indicated Michael Dudley, CEO and co-founder of TransCode. Dr. Zdravka Medarova, TransCode’s CTO and scientific co-founder, indicated that “the TTX delivery platform has already been shown in our preclinical studies to successfully deliver RNA therapeutics to oncology targets, including using small interfering RNAs, antisense oligonucleotides, and non-coding RNA mimics. Recent updates to our company website include an animation that showcases our delivery platform as well as the MOA of our lead therapeutic candidate, TTX-MC138.” Medarova continued, “We are looking forward to moving into the clinic to evaluate our therapeutic candidates in patients and to potentially translate our preclinical success to cancer patients around the world.” The study was conducted in collaboration with Dr. Byunghee Yoo, a faculty member of the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital and Harvard Medical School. The Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital is one of the world’s premier research centers devoted to development and application of advanced biomedical imaging technologies. The Center is part of the Department of Radiology at Massachusetts General Hospital and affiliated with both Harvard Medical School and the Massachusetts Institute of Technology. About TransCode Therapeutics TransCode is an RNA oncology company created on the belief that cancer can be effectively treated using RNA therapeutics. The Company has created a platform of drug candidates designed to target a variety of tumor types with the objective of significantly improving patient outcomes. The Company’s lead therapeutic candidate, TTX-MC138, is focused on treating metastatic cancer, which is believed to cause approximately 90% of all cancer deaths totaling over nine million per year worldwide. The Company believes that TTX-MC138 has the potential to produce regression without recurrence in a range of cancers, including breast, pancreatic, ovarian and colon cancer, glioblastomas and others. Two of the Company’s other drug candidates, TTX-siPDL1 and TTX-siLIN28B, focus on treating tumors by targeting PD-L1 and LIN28B, respectively. TransCode also has three cancer-agnostic programs: TTX-RIGA, an RNA–based agonist of the retinoic acid-inducible gene I, or RIG-I, designed to drive an immune response in the tumor microenvironment; TTX-CRISPR, a CRISPR/Cas9–based therapy platform for the repair or elimination of cancer-causing genes inside tumor cells; and TTX-mRNA, an mRNA-based platform for the development of cancer vaccines designed to activate cytotoxic immune responses against tumor cells.

SAN DIEGO, Oct. 20, 2022 (GLOBE NEWSWIRE) -- Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced a clinical trial collaboration and supply agreement (CTCSA) with Pfizer Inc. (NYSE: PFE) for the CDK4/6 inhibitor palbociclib (IBRANCE®). This agreement will support a clinical proof-of-concept study evaluating ERAS-007, an oral ERK1/2 inhibitor, in combination with palbociclib for the treatment of patients with KRAS- and NRAS-mutant colorectal cancer (CRC) and KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). The combination is currently being investigated as part of the ongoing Phase 1b/2 HERKULES-3 master protocol clinical trial in patients with gastrointestinal (GI) malignancies. Erasca is sponsoring the study, and Pfizer is supplying palbociclib at no cost. “We are excited to expand our existing relationship with Pfizer to explore ERAS-007 in combination with palbociclib in RAS-mutated GI malignancies as part of our HERKULES-3 program,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “Preclinical evidence supports synergistic anti-tumor effects when downstream RAS/MAPK pathway inhibition is combined with cell cycle inhibition in CRC and PDAC. ERAS-007 blocks RAS/MAPK pathway signaling at the terminal node with robust inhibitory activity across RAS mutations, while data support palbociclib inhibition of CDK4/6 leading to cell cycle arrest. Based on their respective mechanisms of action, ERAS-007 and palbociclib offer a promising combination to overcome adaptive resistance in patients with these highly prevalent oncogenic drivers.” Worldwide, approximately 1.8 million cases of CRC are diagnosed annually, with about 50% of patients harboring KRAS or NRAS mutations. PDAC accounts for an estimated 0.5 million new cases diagnosed annually, with over 90% harboring a KRAS mutation. Lack of effective treatment availability and emergence of compensatory mechanisms of resistance continue to challenge the ability to achieve and maintain responses in these GI malignancies. Erasca is exploring whether inhibiting ERK1/2, the terminal node of the RAS/MAPK signaling pathway, in combination with palbociclib can limit the development of treatment resistance and further improve therapeutic benefits. About ERAS-007 ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the RAS/MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. ERAS-007 is being investigated across a series of HERKULES clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer (NSCLC). HERKULES-3 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with GI cancers. About Erasca At Erasca, our name is our mission: To erase cancer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of cancer. We have assembled what we believe to be the deepest RAS/MAPK pathway-focused pipeline in the industry. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer.

ORINDA, Calif. and SEOUL, South Korea, Aug. 18, 2022 /PRNewswire/ -- CG Pharmaceuticals, Inc. announced the first patient dosed with the ivaltinostat and capecitabine combination therapy for the Phase 1b/2 pancreatic adenocarcinoma (PDAC) maintenance study. Commencement of treatment for the first patient began on Aug 15, 2022, and the study will continue to recruit patients in approximately 25 institutions throughout the US. The Phase 1b study will investigate the safety and tolerability of ivaltinostat in 3 different dose cohorts with locally advanced or metastatic PDAC who have completed at least one prior therapy. In the Phase 2 study, metastatic PDAC patients who show no evidence of disease progression after treatment with FOLFIRINOX will receive either the ivaltinostat/capecitabine combination therapy or capecitabine monotherapy after randomization. The primary endpoint is to evaluate ivaltinostat's effect on improving progression free survival (PFS), while key secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Dr. Joong Myung Cho, CEO of CG Pharmaceuticals and CrystalGenomics, stated "Dosing of the first patient is a significant milestone for ivaltinostat as there is a great unmet medical need for the PDAC patients. We are very excited about the start of this trial as ivaltinostat has demonstrated promising signs of efficacy from previous preclinical and clinical studies." About Ivaltinostat Ivaltinostat is a novel anticancer therapeutic candidate that inhibits enzymatic activity of histone deacetylase (HDAC). Ivaltinostat has been evaluated for anticancer effect for metastatic PDAC and myelodysplastic syndrome (MDS). The results of the Phase 2 study with unresectable or metastatic PDAC patients who have not had prior treatment were 93.8%, 25%, and 10.8 months, respectively for DCR, ORR and median OS. These results were published in the June 2022 publication of "International Journal of Cancer". About CG Pharmaceuticals CG Pharmaceuticals, Inc. is a wholly owned US subsidiary of CrystalGenomics, Inc. and was established in 2006 with the focus on the clinical development of CrystalGenomics' pipeline of innovative new drugs in oncology. CG Pharmaceuticals is located in the San Francisco Bay Area. About CrystalGenomics CrystalGenomics, is a commercial stage biopharmaceutical company focused on structure-based drug discovery, development, and commercialization of novel therapeutics in unmet medical need areas of pain/inflammation, oncology, and infectious disease. For more information, please visit: www.crystalgenomics.com. CrystalGenomics is listed on KOSDAQ (083790).