Under your skin

These are the words of Nathan Caffo, president of Presage Biosciences, a biotechnology company focused on the bringing the earliest human efficacy data possible into cancer drug development, before Phase 1 clinical trials. “Our proprietary technology platform allows for the rapid, reliable assessment of multiple cancer therapeutics in an in-vivo setting, providing the first side-by-side comparison of multiple drugs and drug combinations within a single living tumor,” he adds.

Caffo explains that the CIVO arrayed microinjection platform technology came out of the work of a pediatric oncologist, Dr. James Olson, at the Fred Hutchinson Cancer Research Center, also in Seattle. Presage was founded in 2008 based on the licensing of that technology which Olson was using to overcome the limitations inherent in the evaluation of cancer drugs.

“Unlike genomic approaches, CIVO directly places drugs or drug combinations into the tumor by going through the skin,” Caffo says. “The CIVO platform allows for simultaneous assessment of multiple drugs or drug combinations directly in a single solid tumor to assess efficacy, resistance and drug synergies. Now we’re applying it to drug development by delivering it to mouse and dog models to select which drugs work in which subjects and which to advance into further trials.”

Caffo is “very optimistic” that the device can be used to determine the potential of all drugs. Presage is beginning a human feasibility clinical trial with 12 lymphoma patients at the Seattle Cancer Care Alliance, and Caffo expects results by the second quarter of 2015. The study is being done in collaboration with the National Institutes of Health, National Cancer Institute and Fred Hutchinson Cancer Research Center, evaluating response to locally injected drugs from the R-CHOP regimen in lymphoma patients and evaluating the safety profile of CIVO microinjections. CIVO is also being evaluated in preclinical models including canine cancer patients and xenograft human tumors in mice.

Presage presented preclinical data showing that microinjection of several standard-of-care cancer drugs using its CIVO arrayed microinjection platform correlated with drug effects on tumor growth mediated by conventional systemic dosing of the drugs in a poster session at the American Association for Cancer Research 2014 Annual Meeting in San Diego. The CIVO platform allows for simultaneous assessment of multiple drugs or drug combinations directly in a single solid tumor to assess efficacy, resistance and drug synergies. This data provides proof of concept for CIVO, which can provide predictive and more efficient in-vivo testing in animal models and also sets the stage for a new type of pre-Phase 1 toxicity-sparing comparative drug efficacy study in humans.

In a poster presentation entitled “A Platform to Assess Multiple Therapy Options Simultaneously in a Patient’s Own Tumor,” Presage researchers presented results showing that arrayed drug microinjections via the CIVO device induced spatially defined, mechanism-specific tumor responses. In addition, CIVO analysis revealed that these outcomes correlated with responses to systemically delivered drugs and also identified preexisting resistance to chemotherapy.

Specifically, in this study, precise, controlled delivery of cytotoxic chemotherapy drugs vincristine and doxorubicin induced spatially defined, readily detectable and mechanism-specific cellular changes around sites of tumor microinjection across three xenograft models of lymphoma. The extent of apoptosis induced via CIVO microdosing of each drug (less than 100 times the effective dose used to treat human patients) correlated with drug effects on tumor growth followed by conventional systemic dosing of the drug. Responses to both vincristine and doxorubicin were greatly reduced in tumors derived from cells that had previously acquired resistance to doxorubicin.

Presage partners with oncology-focused pharmaceutical companies through strategic alliances to provide in-vivo data to validate novel targets, promote drug candidates to the right indications and discover effective drug combinations in drug development situations where it would otherwise be impractical or impossible to obtain. The company is actively pursuing drug compounds to in-license and is using CIVO to develop a portfolio of promising oncology therapies to advance to the clinic.

“The commercial potential is huge,” Caffo concludes. “We can obtain efficacy data a few years earlier with a small, safe dose. Drug companies can save hundreds of millions of dollars and know that they can do clinical trials that are not doomed to fail.”