Are there many things sweeter than three scoops of ice cream, whether in a cone or a bowl and whether unadorned or part of a sundae or banana split? Well, I don’t have any ice cream to offer via DDNews, but I do have three examples of preclinical research data shared at the 2017 American Association for Cancer Research (AACR) Annual Meeting held recently, from Immunovaccine Inc., Idera Pharmaceuticals Inc. and Sunesis Pharmaceuticals.
Also, these aren’t the only sweet research treats this month from AACR 2017. Starting on page 29, we have a four-page wrap-up of some of the news coming out of that conference.
Monoclonal antibodies can boost efficacy of DepoVax
HALIFAX, Nova Scotia—Immunovaccine Inc, a clinical-stage immuno-oncology company, announced that new preclinical data have demonstrated that phosphatidylserine (PS)-targeting antibodies can enhance the anticancer activity of its DepoVax-based therapeutic vaccine platform.
In the study, researchers combined a Peregrine Pharmaceuticals’ PS-targeting antibody compound (mch1N11) with a DepoVax-based HPV16 peptide vaccine and metronomic cyclophosphamide (mCPA). This combined immunotherapy prolonged survival in C3 mouse models as compared to mice receiving an isotope control in combination with DepoVax/mCPA. Additional analysis also demonstrated an increase in T cells in the tumor following treatment. Taken together, researchers believe that the data suggests that the antibody targeting PS can increase the antitumor immune response induced by a DepoVax-based cancer immunotherapy.
“This study is another step in our exploration of combining DepoVax-based cancer vaccines and other promising immuno-modulatory compounds,” said Dr. Marianne Stanford, vice president of research for Immunovaccine. “Our process of generating supportive preclinical data to guide a potential clinical path forward has been effective in identifying these novel combinations in the past. We now look forward to continued work with our partners to advance combination candidates into and through the clinic, with the goal of expanding treatment options for hard-to-treat cancers.”
DepoVax is a patented formulation that provides controlled and prolonged exposure of antigens plus adjuvant to the immune system, resulting in a strong, specific and sustained immune response with the potential for single-dose effectiveness. The DepoVax platform is said to be flexible and usable with a broad range of target antigens for preventative or therapeutic applications.
Idera shares preclinical and clinical data on IMO-2125
HOUSTON—Also at AACR 2017, Idera Pharmaceuticals, a clinical-stage biopharmaceutical company developing Toll-like receptor and RNA therapeutics for patients with cancer and rare diseases, reported additional clinical translational and preclinical data from its ongoing intratumoral IMO-2125 development program.
One poster presentation, titled “Local treatment with novel TLR9 agonist IMO-2125 demonstrates antitumor activity in preclinical models of pancreatic cancer”—which was presented by Dr. Daqing Wang, a principal scientist and group leader at Idera Pharmaceuticals, demonstrated that intratumoral IMO-2125 showed dose-dependent antitumor responses associated with the increased tumor-infiltrating lymphocytes (TILs) in treated tumors of the Panc02 pancreatic cancer model. These antitumor responses and TILs were also observed in the distant, untreated tumors. In this study, treated mice, which remained tumor-free, showed lack of tumor growth upon rechallenge with the same tumor cells, suggesting an antitumor memory response.
Furthermore, a local treatment of IMO-2125 was evaluated by administering intraperitoneally in a peritoneal metastasis Panc02 model. Mice treated with intraperitoneal IMO-2125 showed increased survival compared to mice treated with placebo, control oligo compound or subcutaneous IMO-2125. Histological analysis showed significant reduction of tumor growth in the peritoneal cavity.
“Overall, we believe these data demonstrate that treatment with IMO-2125 modulates the tumor microenvironment and increases infiltration by TILs, and that these changes are associated with antitumor activity in pancreatic cancer models and indicate that IMO-2125 may potentiate checkpoint inhibitor therapy for the treatment of pancreatic cancer,” the company reported.
Idera also shared clinical data in a poster titled “Translational evidence of reactivated innate and adaptive immunity with intratumoral IMO-2125 in combination with systemic checkpoint inhibitors from a Phase 1/2 study in patients with anti-PD-1 refractory metastatic melanoma,” presented by Dr. Cara Haymaker of the University of Texas MD Anderson Cancer Center. The key findings in Haymaker’s presentation were that intratumoral IMO-2125 monotherapy in the injected lesions results in activation and maturation of dendritic cells and the induction of type-1 interferon gene signature by 24 hours after first dose.
BTK inhibitor vs. CLL
SOUTH SAN FRANCISCO, Calif.—Sunesis Pharmaceuticals, for its part, announced results from an Ohio State University-sponsored preclinical study evaluating the efficacy of non-covalent BTK inhibitor SNS-062 in chronic lymphocytic leukemia (CLL) proprietary cell lines and patient samples. The study demonstrated that, unlike ibrutinib, SNS-062 inhibition of BTK signaling is unaffected by the presence of the C481S mutation and may address acquired resistance to covalent BTK inhibitors. The results were presented at AACR 2017 in a poster session titled “Reversal of Drug Resistance.”
“B-cell receptor signaling is exceptionally active in CLL and is vital for the proliferation and survival of CLL cells, making BTK inhibition an effective target. However, a subset of patients acquire resistance to ibrutinib, the current standard-of-care BTK inhibitor,” said Dr. Amy Johnson, an associate professor of hematology at Ohio State University. “A key resistance mechanism to covalent BTK inhibitors is a point mutation in the BTK active site, converting cysteine 481 to serine, or C481S. In this study, we demonstrate that SNS-062, which binds non-covalently to BTK, is a potent inhibitor of BTK unaffected by the presence of the C481S mutation. These findings support clinical investigation of SNS-062 to address acquired resistance to covalent BTK inhibitors in patients.”
“Preclinical and healthy volunteer data continue to reveal a unique profile for SNS-062, one distinct from ibrutinib and other covalently binding BTK inhibitors,” said Dr. Judy Fox, chief scientific officer of Sunesis. “SNS-062 has the potential to become an important new treatment for CLL, addressing what is an increasingly well-defined and prevalent unmet patient need. With an active IND, we remain on track to dose the first patient in our planned Phase 1b/2 study in patients with advanced B cell malignancies this quarter.”
