Prolynx LLC

Aug. 21, 2024 -- ProLynx Inc. today announced the use of their technology to create a long-acting semaglutide that can be administered once monthly. The ProLynx technology involves tethering a therapeutic to hydrogel microspheres via linkers with tunable, pre-programmed release rates. Semaglutide is a peptide GLP-1 agonist that is the active ingredient in the Novo Nordisk blockbuster drugs Ozempic® and Wegovy®; Ozempic® is used to treat Type 2 diabetes, whereas Wegovy® is a higher-dose version approved for weight loss. Combined sales of these drugs reached about $20 billion in 2023, and demand exceeded supply. Semaglutide has a half-life of about 160 hours and, as with most anti-obesity peptides, must be administered once weekly. All peptide drugs have short half-lives and require some form of half-life extension. Almost all of the current anti-obesity drugs, including semaglutide, are "lipidated" peptides – attached to a fatty acid – that require once weekly injections. The ProLynx long-acting semaglutide was targeted for once monthly administration, and pharmacokinetic experiments verified an extended half-life of about 30 days in mice. Importantly, a single injection in diet-induced obese mice showed about a 20% weight loss after 30 days, comparable to multiple injections of semaglutide over the same period. Daniel Santi, co-founder and President of ProLynx, stated, “Our long-acting semaglutide is compelling because it uses the very same semaglutide that is already approved by the FDA and well-known to patients. The technology simply converts the once weekly drug to one that can be administered once monthly. Previously, ProLynx developed a long-acting monthly peptide GLP-1 agonist as an agent for the treatment of type-2 diabetes (Schneider et al., ACS Chem. Biol. 2017), but this is the first time we achieved this with a lipidated peptide.” Using the same approach, ProLynx envisions converting other lipidated peptides of high current interest from once weekly to once monthly administration. Additionally, simulations indicate that the long half-lives and high potencies of some GLP-1 agonists might allow for dosing every three or more months. This could be particularly important in certain patient populations because dosing could coincide with doctor’s visits. ProLynx is a San Francisco biotechnology company developing proprietary systems to extend the half-life and improve pharmacokinetics and efficacy, while reducing toxicities of important therapies. ProLynx focuses efforts on areas of unmet needs that its technology can uniquely fill (www.ProLynxinc.com). Contact: BD@ProLynxinc.com The content above comes from the network. if any infringement, please contact us to modify.

SAN FRANCISCO, March 25, 2024 (GLOBE NEWSWIRE) -- ProLynx Inc. announced that the first patient was included in TOPOLOGY by investigator Dr. Delphine Loirat, with a Phase II clinical trial investigating PLX038 (PEG~SN-38) for locally-advanced or metastatic triple-negative breast cancer (TNBC). Patients will have been previously treated with at least two therapies, including the antibody-drug conjugate (ADC) sacituzumab govitecan (SG; Trodelvy). The TOPOLOGY trial is run by Institut Curie (Paris and Saint Cloud, France), with principal investigator Prof. Francois-Clement Bidard . PLX038 is a long-acting prodrug of the topoisomerase 1 (Top1) inhibitor, SN-38, which is also the active component of anti-cancer agents irinotecan and the ADC SC. Top1 inhibitors cause DNA breaks and kill tumors that are unable to repair the damage. Previously, Curie researchers showed that about one-third of TNBC patients have defects in DNA damage repair, and should respond to an effective SN-38-based therapy (Coussy et al., 2020). In PLX038, SN-38 is covalently bound to a circulating nanoparticle and is slowly released to provide free SN-38 with a long half-life, low Cmax, and high exposure – important facets for optimal safety and efficacy. Importantly, in preclinical studies PLX038 was shown to accumulate and be retained in solid tumors, where it slowly releases its SN-38. SG is an anti-TROP2 ADC with an SN-38 payload that was recently approved for use in advanced TNBC. However, the rapid spontaneous linker hydrolysis in SG releases a large amount of SN-38 cargo systemically, which may in part contribute to its efficacy and also in part be responsible for systemic side effects. Unfortunately, the median progression-free survival after SG therapy is only ~6 months due to resistance, and there are limited rescue therapies available. ProLynx co-founder and President Daniel V. Santi commented, “Although the active SN-38 payload of PLX038 and SG is the same, the anti-tumor mechanisms of the prodrugs are quite different; and, some mechanisms of resistance may also quite be different (Santi et al., Biodrugs,2024). Taken together, it is reasonable to believe that PLX038 may be effective in SG-resistant tumors.” Curie investigator Francois-Clement Bidard added, “As with our earlier preclinical study of the correlation of efficacy of irinotecan with BRCAness and SFLN11 biomarkers, TOPOLOGY will assess association of PLX038 efficacy with homologous recombination defects, and biomarkers such as SFLN11 expression and RB1 loss. If confirmed in TOPOLOGY, these biomarkers will allow pre-selection of patients most likely to respond to the drug.” ProLynx is a San Francisco biotechnology company developing proprietary systems to improve the pharmacokinetics and efficacy of important therapies ( ). Institut Curie, France’s leading cancer center, combines a renowned research center and hospital which treats all types of cancer. Institut Curie has 3 sites (Paris, Saint-Cloud and Orsay) with over 3,700 health professionals working on treatment, research and teaching ( ) Information on this clinical trial is available at clinicaltrials.gov, NCT06162351. Contact BD@ProLyninc.com

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 ( ).