Recent advances in pancreatic cancer research have shown that many heparin-binding factors are involved in tumor progression, including sonic hedgehog, VEGF, FGF-2, PDGF, SDF-1, IGF, and HGF. Momenta developed M402 as a mimetic to heparan sulfate, which are sugar molecules on cell surfaces that regulate growth factors, cytokines, chemokines, and adhesion molecules. By inhibiting the accumulation and activity of these factors at the local sites, M402 has been shown to inhibit tumor progression, adhesion, angiogenesis and metastasis in preclinical studies.
Researchers conducted a series of experiments using two different pancreatic cancer models to test the hypothesis that M402 can modulate tumor progression and metastasis and enhance the efficacy of gemcitabine, a first-line standard of care chemotherapy treatment for pancreatic cancer. The results showed that M402 in combination with gemcitabine was effective in both models, each targeting different mechanisms. Specifically, in a genetically engineered model, M402 inhibited epithelial-to-mesenchymal transition, a mechanism by which tumor cells can revert to a stem cell-like phenotype that is more resistant to chemotherapy. In an orthotopic xenograft model, M402 inhibited desmoplasia, a fibrotic response in the tumor that hinders drug penetration and promotes invasion and also metastasis. The poster, titled: "M402, a Heparan Sulfate Mimetic and Novel Candidate for the Treatment of Pancreatic Cancer," is available on the Momenta website at www.momentapharma.com
"These data provide important insight into the potential clinical benefits of inhibiting multiple signaling pathways with M402, and further support the rationale for the evaluation of this drug candidate in our ongoing Phase 1/2 clinical trial for pancreatic cancer," said
M402 is a novel heparan sulfate mimetic that binds to multiple growth factors, adhesion molecules and chemokines to inhibit tumor angiogenesis, progression, and metastasis. The use of heparins to treat venous thrombosis in cancer patients has generated numerous reports of antitumor activity; however, the dose of these drugs has been limited by their anticoagulant activity. M402, which is derived from unfractionated heparin, has been engineered to have significantly reduced anticoagulant activity while preserving the relevant antitumor properties of heparin. Ideally, higher doses of M402 could potentially be administered to further enhance these antitumor properties. M402 has the potential to complement conventional chemotherapy, and as M402 has the ability to bind to multiple heparin binding factors, it may play a role in a broad range of cancers. M402 is currently being evaluated in a Phase 1/2 clinical trial for metastatic pancreatic cancer. The trial is evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of escalating M402 doses in combination with gemcitabine.
About Pancreatic Cancer
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Lora Pike Momenta Pharmaceuticalslpike@momentapharma.com 617-395-5189
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