Trovagene Announces Patent for Combination of Onvansertib with Anti-Androgen Drugs

Trovagene announced the issuance of a new patent (10,155,006), entitled Combination Therapies and Methods of Use Thereof for Treating Cancer, by the U.S. Patent and Trademark Office (USPTO). This patent broadens previously issued patent (9,566,280), by expanding the use of Onvansertib to encompass combination therapies with any anti-androgen and androgen antagonist drug, such as Zytiga, Xtandi and Erleada for the treatment of metastatic and non-metastatic castrate-resistant prostate cancer.

The issuance of this patent further strengthens Trovagene's existing intellectual property portfolio obtained with the licensing of exclusive global development and commercialization rights to Onvansertib, a first-in-class, 3rd generation Polo-like Kinase 1(PLK1) inhibitor, from Nerviano Medical Sciences (NMS).

"There is a need for new therapies that effectively treat cancers that depend on internal androgen signaling, such as castration-resistance prostate cancer, as well as cancers which overexpress androgen receptor (AR), or are otherwise dependent on the synthesis of steroid hormones for their growth," said Dr. Michael Yaffe, Director, MIT Center for Precision Cancer Medicine, David H. Koch Professor in Science, Professor of Biological Engineering, and member of the Koch Institute for Integrative Cancer Research.

"The novel discovery by Dr. Yaffe and his team at MIT, demonstrating synergy with the combination of Onvansertib with anti-androgens, was fundamental to initiating our now ongoing Phase 2 trial of Onvansertib in combination with Zytiga (abiraterone acetate) for the treatment of metastatic Castration-Resistant Prostate Cancer (mCRPC), which is being conducted by the Harvard Medical Cancer Centers," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "The issuance of this new patent expands the potential market opportunity for Onvansertib in both metastatic and non-metastatic prostate cancer with combination regimens that include multibillion-dollar drugs Zytiga®, Xtandi and Erleada."

In this multi-center, open-label, Phase 2 trial, Onvansertib in combination with the standard dose of Zytiga (abiraterone acetate) and prednisone, all administered orally, is being evaluated for safety and efficacy. The trial will enroll up to 45 patients with mCRPC showing early signs of disease progression demonstrated by two rising PSA values separated by at least one week, while on Zytiga/prednisone therapy. The primary efficacy endpoint is the proportion of patients achieving disease control after 12 weeks of study treatment, as defined by lack of prostate specific antigen (PSA) progression in patients who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving abiraterone acetate and prednisone.

Onvansertib is a first-in-class, 3rd generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors. Separate studies with other PLK inhibitors have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates of up to 31% were observed when combined with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. A Phase 1 open-label, dose escalation safety study of Onvansertib has been completed in patients with advanced metastatic solid tumor cancers and published in Investigational New Drugs. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) in this trial was 24 mg/m2. Trovagene has an ongoing Phase 1b/2 clinical trial with Onvansertib in AML that was accepted by the National Library of Medicine (NLM) and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. Onvansertib has been granted Orphan Drug Designation by the FDA in the U.S. and by the EC in the European Union (EU) for the treatment of patients with AML.

Onvansertib targets the PLK1 isoform only, is orally administered, has a 24-hour drug half-life with only mild to moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK1 inhibitor, Onvansertib, with other compounds has the potential to improve clinical efficacy in Acute Myeloid Leukemia (AML), metastatic Castration-Resistant Prostate Cancer (mCRPC), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast Cancer (TNBC), as well as other types of cancer.

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