Halozyme Therapeutics, Inc. (HALO), a biotechnology company developing novel oncology and drug-delivery therapies, demonstrated in preclinical models that its investigational drug PEGPH20 increases the number of cancer-fighting white blood cells accumulating in the tumor and the effectiveness of immunotherapies. The research was presented at the 108th annual meeting of the American Association of Cancer Research (AACR) and builds upon prior preclinical findings.
“We are encouraged that these findings from our animal models continue to support the potential benefits of remodeling the tumor microenvironment in stimulating an immune response and improving the efficacy of checkpoint inhibitors and cell-based immunotherapies,” said Dr. Helen Torley, president and CEO. “We are pleased that PEGPH20 continues to demonstrate significantly improved tumor growth inhibition in certain hard-to-treat hyaluronan-rich cancer models when administered in combination with additional cancer fighting agents.”
PEGPH20 is a proprietary enzyme that targets and degrades hyaluronan (HA), a glycosaminoglycan or naturally occurring sugar in the body. HA accumulates in higher concentrations around many solid tumors, potentially constricting blood vessels, impeding the immune response and the access of other therapies.
Research to be presented includes data from a breast cancer mouse model treated with PEGPH20 which showed a significant increase in the accumulation of cancer-fighting CD8+ T cells, also called tumor infiltrating lymphocytes (TILs), compared to mice untreated with PEGPH20. Additional research shows that PEGPH20 administered in combination with an anti-PD-L1 immune checkpoint inhibitor and with Aduro’s Listeria-based vaccine immunotherapy facilitated CD8+ T-cell accumulation and improved effectiveness over what was achieved with either the anti-PD-L1 or Listeria immunotherapy alone.
PEGPH20 increased the anti-PD-L1 effectiveness by 411 percent compared to anti-PD-L1 alone as measured by tumor growth inhibition (93% vs 18.2%, p<0.0001) and increased the accumulation of CD8+ T cells by 176 percent (p=0.0025) in an HA-rich mouse model. Taken together, these data suggest that tumor HA accumulation may act as a barrier to immune cell access and that PEGPH20-mediated HA reduction facilitates increased access of CD8+ T cells.
Halozyme and other researchers are conducting further investigations to determine the potential of combining PEGPH20 with adoptive T cell and other immunotherapies. Halozyme has ongoing clinical studies of PEGPH20 in combination with chemotherapy and immunotherapies, with plans to initiate new studies in a previously announced clinical collaboration with Genentech combining PEGPH20 with atezolizumab, an anti-PD-L1 therapy, in up to eight tumor types.
Halozyme’s AACR abstracts include:
PEGylated recombinant hyaluronidase PH20 (PEGPH20) enhances tumor infiltrating CD8+ T-cell accumulation and improves checkpoint inhibitor efficacy in murine syngeneic breast cancer models. Abstract 641. Sunday, April 2, 1 to 5 p.m. ET
HTI-1511, a novel anti-EGFR-ADC, overcomes mutation resistance and demonstrates significant activity against multiple tumor types in preclinical studies. Abstract 50. Sunday, April 2, 1 to 5 p.m. ET
Evaluating clinically relevant pharmacological agents in a rat ambulation model to ameliorate PEGylated recombinant hyaluronidase PH20 (PEGPH20)-mediated musculoskeletal adverse events. Abstract 1240. Monday, April 3, 8 a.m. to noon ET
A Phase 1b study of PEGPH20 plus pembrolizumab in patients with selected hyaluronan-high solid tumors. Abstract CT032. Monday, April 3, 8 a.m. to noon ET.
Global phase 3, randomized, double-blind, placebo-controlled study evaluating PEGylated recombinant human hyaluronidase PH20 (PEGPH20) plus nab-paclitaxel and gemcitabine in patients with previously untreated, hyaluronan (HA)-high, stage IV pancreatic ductal adenocarcinoma. Abstract CT066. Monday, April 3, 1 to 5 p.m. ET
Combination of PEGylated recombinant hyaluronidase PH20 (PEGPH20) with Live-attenuated, Double-Deleted (LADD) Listeria enhances tumor infiltrating
CD8+ T cell response and antitumor efficacy in mice. Abstract LB-198. Tuesday, April 4, 8 a.m. to noon ET