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Home Research & Development News Presage Biosciences presents data demonstrating superior tumour growth inhibition by voruciclib and proteasome inhibitors
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20 Apr 2016

Presage Biosciences presents data demonstrating superior tumour growth inhibition by voruciclib and proteasome inhibitors

Data presented at AACR Annual Meeting from CIVO platform.

Presage Biosciences will present preclinical data showing that the company’s clinical-stage oral CDK inhibitor, voruciclib, in combination with proteasome inhibitors, demonstrated superior tumour growth inhibition in xenografts than the single agents separately in a model of triple negative breast cancer (TNBC), a disease which has proven challenging to treat with standard chemotherapy options. The data are being presented today at the American Association for Cancer Research (AACR) 2016 Annual Meeting in New Orleans.

In a poster presentation entitled “Voruciclib, a clinical stage CDK inhibitor sensitizes triple negative breast cancer xenografts to proteasome inhibition,” Presage researchers present results from a study using the Presage CIVO platform, which allows for simultaneous assessment of multiple drugs or drug combinations directly in a single solid tumor, to identify drug combinations with voruciclib that result in synergistic anti-tumor activity in the HCC1187 model of triple negative breast cancer:

  • Because voruciclib demonstrates potent activity against CDK 9, the study aimed to identify agents that result in induction of pro-survival regulators such as MCL-1, a direct target of CDK 9, as good candidates for combination with voruciclib.

  • In a CIVO screen with a number of drugs for possible combinations, bortezomib, a proteasome inhibitor, induced the highest localized expression of MCL-1.

    • Injecting voruciclib and bortezomib in combination directly into tumours led to robust localized anti-tumour activity.

    • In contrast, exposure to either voruciclib or bortezomib as single agents showed limited anti-tumour activity.

    • The combination effect with voruciclib also was present when injected in combination with other proteasome inhibitors, including next-generation oral proteasome inhibitor MLN2238.

    • Again, no significant impact on tumour progression was observed in xenografted subjects treated with either voruciclib or MLN2238 as single agents.

  • In addition, the results obtained with CIVO accurately predicted the outcome of systemic drug efficacy studies where tumour regression or stasis were induced by combining voruciclib with either bortezomib or MLN2238.

    • Presage is developing voruciclib, a clinical-stage oral CDK inhibitor, in combination with other agents identified through CIVO, an in vivo assessment technology intended for drug development to enable the first side-by-side comparison of multiple drugs and combinations within a single living tumor while still in a patient’s body, without exposing the patient to the toxicity associated with systemically dosed drugs.

    “The CIVO platform has enabled us to rapidly gain a better understanding of the unique biology of tumour response to voruciclib, particularly in combination with other agents,” said Nathan Caffo, President of Presage. “We expect to apply these findings as Presage develops voruciclib drug combinations in the clinic to hopefully provide more effective treatments for patients with cancer.”

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