DFP-13318

SAN FRANCISCO, Feb. 05, 2024 (GLOBE NEWSWIRE) -- ProLynx Inc. announced today that the first patient was treated with PLX038 (PEGylated SN-38) in a Phase I/II clinical trial for primary CNS tumors driven by MYC or MYCN amplifications. National Institutes of Health’s NCI investigators Dr. Marta Penas-Prado and Dr. Mark Gilbert are conducting the trial. MYC genes regulate expression of genes involved in cell division. High levels of MYC drive oncogenesis in many cancers and induce DNA changes leading to the formation of “topoisome complexes”. MYC and MYCN amplifications are seen in multiple primary tumors of the central nervous system (CNS). This includes 30% of relapsed medulloblastomas, and MYCN-amplified ependymoma, characterized by aggressive clinical behavior and treatment resistance. The MYC or MYCN-induced topoisome contains high levels of topoisomerases that should be susceptible to topoisomerase inhibitors. PLX038 is a long-acting prodrug of the topoisomerase 1 inhibitor, SN-38 – the active metabolite of irinotecan and sacituzumab govitecan. PLX038 is unique as the SN-38 is covalently bound to a circulating nanomolecule and is slowly released to provide free SN-38 with a long half-life, low Cmax and very high exposure – important for optimal safety and efficacy. Importantly, in preclinical studies, PLX038 was shown to accumulate in CNS tumors, where it slowly releases SN-38. The NCI trial will assess whether PLX038 is safe and efficacious in primary CNS tumors driven by MYC or MYCN amplifications. The Phase I trial will confirm the recommended Phase II dose. The Phase II trial will test PLX038 in 3 independent cohorts: 1) newly diagnosed MYCN-amplified ependymoma, 2) recurrent ependymoma or medulloblastoma with MYCN or MYC amplification, and 3) other recurrent primary CNS tumors with MYC or MYCN amplifications. Notably, the Phase II trial will incorporate on-treatment tumor biopsies to investigate biomarkers of response and resistance, including SLFN11, MYC, MYCN and Top1, 2a, and 2b expression. This data could prospectively identify patients most responsive to the drug. Additionally, working collaboratively with The Office of Patient-Centered Outcomes (OPCORe), researchers will collect patient-reported outcomes (PROs) to measure the impact of therapy, including toxicity, symptom severity and interference with daily activities, and physical functioning. ProLynx co-founder, Daniel V. Santi, stated, “We are excited to work with NCI investigators to bring novel treatments to patients with rare CNS cancers, in hope of improving their outcomes.” He added, “Conventional short-acting topoisomerase 1 inhibitors have clinical activity in certain CNS tumors. Accordingly, we are optimistic that a long-acting SN-38 will result in increased efficacy and safety.” Additional information on this clinical trial is available at clinicaltrials.gov, through identifier number NCT06161519. For patients interested in enrolling in this clinical trial, please call NCI’s toll-free number: 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615); visit the website: and/or email: NCIMO_referrals@mail.nih.gov. ProLynx is a San Francisco biotechnology company developing proprietary systems to improve the pharmacokinetics/efficacy of important drugs ( ).

SAN FRANCISCO, Jan. 24, 2024 (GLOBE NEWSWIRE) -- ProLynx Inc., a biotech company with a unique technology for tunable half-life extension of drugs, announced publication of a paper entitled “Could a Long-Acting Prodrug of SN-38 be Efficacious in Sacituzumab Govitecan-Resistant Tumors?” in BioDrugs In the article the authors inform: “Sacituzumab govitecan (Trodelvy®) is an antibody drug conjugate (ADC) of a humanized anti-TROP2 monoclonal antibody (mAb), linked to SN-38 — the active metabolite of the anti-cancer drug irinotecan and a potent inhibitor of topoisomerase 1. Sacituzumab govitecan has been remarkably effective in many clinical trials and is FDA-approved for patients with metastatic triple-negative breast cancer (TNBC) and pre-treated HR+/ HER2- metastatic breast cancer. Unfortunately, the median progression-free survival is only about 6 months due to resistance, and there are limited rescue therapies available.” The authors of the publication argue that sacituzumab govitecan is not a conventional ADC since it spontaneously releases a high level of the SN-38 in the systemic circulation; the released SN-38 is so high in concentration that it must have activity apart from its action as an ADC payload. Hence, sacituzumab govitecan likely acts as a simple prodrug of systemic SN-38 as well as an ADC. The authors posit that a long-acting SN-38, such as ProLynx PLX038, should be an efficacious and less toxic prodrug of systemic SN-38 than sacituzumab govitecan, and could serve as a therapy for certain forms of resistance mechanisms to sacituzumab govitecan. Daniel Santi, Cofounder and President of ProLynx, stated: “We will know whether our hypothesis is correct after a soon-to-start trial of our long-acting PLX038 in Trodelvy-resistant patients at the Curie institute” {NCT06162351;TOPOLOGY}. About ProLynx. ProLynx is a biotechnology company developing proprietary systems to improve pharmacokinetics, efficacy and safety of proteins, peptides and small molecules. The company is located in San Francisco, CA. For further information see or email BD@ProLynxinc.com.