Halozyme Therapeutics Inc (HALO)

[friendofthedevil]

Targeting Key Vulnerabilities in Pancreatic Cancer

Thursday, October 9, 2014 | 8:00 AM - 4:00 PM
The New York Academy of Sciences


Not sure if there will be any new or surprising data presented here. It is a pretty wonky little conference to present any big results. More likely a bit of a rehashing and summary of animal studies and the Ph1b stuff. Let's hope for an update c/w the (good) old results.

http://www.nyas.org/Events/Detail.aspx?cid=7966ce5f-6057-41f3-bb85-17b28c6081a5

Enzymatic Remodeling of the Pancreatic Ductal Adenocarcinoma Tumor Microenvironment to Improve Chemotherapeutic Efficacy
Curtis B. Thompson, PhD1
Pancreatic ductal adenocarcinoma (PDA) is characterized by a tumor microenvironment (TME) with high stromal desmoplasia, a reduction in vessel density, and poor perfusion, all instrumental in PDAs observed resistance to chemotherapeutic intervention. Hyaluronan (HA), an extracellular matrix glycosaminoglycan, has been shown to accumulate to high levels in approximately 90% of PDA tumors, and is thought to be a key component of this desmoplastic response. In preclinical mouse models, including tumor xenografts, patient-derived tumor xenografts, and genetically engineered mouse models of pancreatic cancer (KPC), depletion of HA from the TME with a pegylated recombinant human hyaluronidase PH20 (PEGPH20) is associated with remodeling of the tumor stroma, reduction of tumor interstitial fluid pressure, expansion of tumor blood vessels and facilitated delivery of chemotherapy. Tumor remodeling following HA depletion appears to be sustained. Studies in the KPC model have shown that increased tumor perfusion following PEGPH20 treatment in combination with gemcitabine persists for weeks after therapy cessation. In other mouse models, PEGPH20-mediated HA removal also induces a partial reversal of the classical epithelial-mesenchymal transition process associated with the progression of malignancy. In view of these findings, a Phase 1b/2 clinical trial to evaluate PEGPH20 in combination with gemcitabine in patients with stage IV metastatic pancreatic cancer was conducted. PEGPH20 plus gemcitabine was well tolerated and showed promising efficacy in patients with high tumor HA, leading to the current clinical phase 2 study of PEGPH20 in combination with nab-paclitaxel and gemcitabine for the treatment of stage IV PDA.

Coauthors: H. Michael Shepard, PhD1 and Daniel C. Maneval, PhD1
1. Halozyme Therapeutics, Inc., San Diego, CA

Speaker:

Curtis B. Thompson, PhD

Halozyme Therapeutics, Inc., San Diego, CA

Dr. Thompson has over 15 years of preclinical experience in the pharmaceutical industry across a broad range of research disciplines, including: hypertension and vascular biology, antisense technology (ssDNA, RNAi), inflammation, osteoporosis and osteoarthritis, asthma and cancer. Curt currently is Senior Director of Pharmacology at Halozyme Therapeutics, Inc, in San Diego, California. His group is responsible for the final design of internal / external experiments in pharmacology supporting the development of new biologics.