Touring the oncology landscape

A roundup of recent preclinical cancer research

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Preclinical oncology researchers continue to make breakthroughs at a thrilling pace, with significant new advances regularly reported. A recently published study outlines how Corvus Pharmaceuticals’ CPI-444 had significant antitumor success when administered alone as a monotherapy and when used in concert with another anti-PD-1 therapy. Likewise, NucleoBio Inc. has released promising results showing its Prostreat drug outperforms commercially available prostate cancer treatments in preliminary animal testing. And, in other positive preclinical news, TRACON Pharmaceuticals recently disseminated data indicating that TRC105, when used in combination with a PD-1 antibody, significantly reduced tumor volume in syngeneic colorectal cancer in mice. Lastly, ContraVir Pharmaceuticals has confirmed its cyclophilin inhibitor reduces both the number and the size of liver tumors in a hepatocellular carcinoma mouse model.

Corvus Pharmaceuticals shows CPI-444 affects several checkpoints
BURLINGAME, Calif.—CPI-444, a selective and potent adenosine A2A receptor inhibitor, is the most promising drug candidate in Corvus Pharmaceuticals’ pipeline, and recent findings suggest more cause for hope. Results published in the journal Cancer Immunology, Immunotherapy detail how CPI-444, when administered as monotherapy, suppressed colorectal tumor growth and improved survival in animal tumor models, and when administered in combination with anti-PD-1 therapy, dramatically improved antitumor immune responses over either agent used alone.
When tested alone on two animal models of colon tumors, CPI-444 suppressed tumor growth and improved survival, even on one tumor known to be resistant to checkpoint blockades. When coupled with anti-PD-1 immunotherapies, which disrupt mechanisms that protect tumors, the combination therapy dramatically improved tumor regression and survival of the animal in both models. In addition, CPI-444 showed broad promise in enhancing immune responses in an animal model of melanoma, suppressed the expression of multiple checkpoint pathways, (particularly in tumor-draining lymph nodes) and increased function of killer T cells in tumor infiltrating cells. Certainly, CPI-444 will be the focus of more studies in the search for more effective targeted oncology therapies.

NucleoBio presents Prostreat as an effective drug to treat prostate cancer
NEW YORK—Using a new technology, NucleoBio scientists created Prostreat in the hopes that it would reduce growth and slow or stop the spread of aggressive and advanced prostate cancer. Dr. Olorunseun Ogunwobi, the NucleoBio co-founder who led the research, utilized synthetic analogs of microRNAs to create Prostreat.
“We created synthetic analogs of specific microRNAs that we identified from our research, and have demonstrated their superior antitumor and antimetastatic properties in aggressive metastatic castration-resistant prostate cancer, as compared to commercially utilized drugs,” Ogunwobi said. “This type of technology is relatively new, and to my knowledge, there is no other synthetic microRNA analog that is used in the treatment of prostate cancer.”
NucleoBio measured Prostreat’s effectiveness in direct comparison to a number of widely available and commonly utilized medications for advanced prostate cancer, including enzalutamide, abiraterone and apalutamide. Their results showed a dramatic improvement in efficacy over the current commercially available drugs, especially in tackling aggressive prostate cancer that commonly manifests the ARV7 mutant protein, which contributes to drug resistance. NucleoBio scientists will be presenting their findings—which include Prostreat’s ability to inhibit the proliferation, migration, growth and metastasis of prostate tumors without any noted toxic side effects in animals—to a peer-reviewed journal later this year, and human clinical trials are slated to commence in the fall.

TRACON Pharmaceuticals unveils TRC105 study data
SAN DIEGO—In more promising news for the treatment of colon cancer, TRACON Pharmaceuticals shared positive data about studies utilizing the endoglin antibody TRC105 in conjunction with a PD-1 antibody. In studies that looked at treatment of immunocompetent mice with induced colorectal cancer with TRC105 alone, with a PD-1 antibody alone and with the two combined, researchers discovered that the combined treatment significantly reduced tumor volume compared to treatment with either antibody alone. While treatment with one or the other improved survival, when used in tandem, 30 to 60 percent of animals saw long-term survival improvement.
Based on a series of studies exploring the utility of TRC105, TRACON believes its activity may be mediated through an immunologic mechanism. In addition, data suggests another endoglin antibody, MI043, may echo the impact of TRC105 in mice. Studies coupling MI043 with PD-1 antibodies show similar synergistic results when used in combination. More data are forthcoming regarding TRC105, as it is currently being tested in a number of clinical trials in differing phases for the treatment of several kinds of cancers.

ContraVir’s CRV431 reduces size and number of liver tumors in mice
EDISON, N.J.—In one more promising development in preclinical oncology, ContraVir Pharmaceuticals has released findings confirming that its CRV431 cyclophilin inhibitor reduced the development and progression of liver tumors in HCC mouse models. Study data indicates a reduction in tumor nodules of 44 percent, coupled with a 56-percent reduction in overall tumor burden in treated mice.
“The results of this preclinical study indicate that CRV431 could offer a potential treatment opportunity for hepatocellular carcinoma (HCC), representing an important pipeline expansion opportunity for ContraVir,” commented James Sapirstein, CEO of ContraVir. “We previously demonstrated that CRV431 reduces key markers of hepatitis B virus, including DNA, HBsAg and pgRNA. This new data provides evidence that CRV431 can also reduce the amount and size of tumors in HCC, bringing us another step closer to our ultimate goal of reducing the burden of liver disease.”

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