Trovagene Company Overview

Trovagene is a clinical-stage, precision medicine oncology therapeutics company. Trovagene’s lead drug candidate, PCM-075, is a Polo-like Kinase 1 (PLK1) selective adenosine triphosphate (ATP) competitive inhibitor.

PCM-075 was developed to have high selectivity to PLK1, to be administered orally, and to have a relatively short drug half-life of approximately 24 hours compared to other PLK inhibitors. PCM-075 has completed a safety study in patients with advanced metastatic solid tumors with a phase 1b/2 clinical trial in patients with AML underway.

PCM-075 has shown preclinical antitumor activity as a single agent and in synergy combinations with more than ten different chemotherapeutics and targeted therapies, such as Zytiga® (abiraterone acetate), Beleodaq® (belinostat), Quizartinib (AC220), a development stage FLT3 inhibitor, and Velcade® (bortezomib) in acute myeloid leukemia (AML), metastatic castration resistant prostate cancer (mCRPC) and other liquid and solid tumor cancers.

PCM-075: Our Lead Product Candidate

Our lead product candidate, PCM-075, was licensed from Nerviano Medical Sciences, S.r.l., a leading European oncology research and discovery organization, and is being developed initially for the treatment of patients with acute myeloid leukemia (AML).

PCM-075 is a highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple hematologic malignancies, as well as solid tumors such as adrenocortical, breast, prostate, ovarian, lung, gastric and colon cancers. PCM-075 is orally bioavailable and has been explored in an initial Phase 1, open-label, dose-escalation safety study in patients with advanced metastatic solid tumor cancers.

Significant Opportunity for New Treatment Options in AML

Acute myeloid leukemia (AML) is a cancer of blood cells and is characterized by the rapid growth of abnormal white blood cells that build up in the blood and bone marrow. While AML is a relatively rare disease, the risk increases with age, and its incidence is expected to grow as the population ages. Currently, the 5-year survival rate is only 25%.

Current treatment includes an intensive chemotherapy regimen that’s been used for over 40 years, and for younger patients, stem cell transplantation, as it can be prohibitively toxic for older patients. Consequently, there is significant opportunity for new treatment options.

PCM-075 Clinical Development Plan in AML

Preclinical and Phase 1 data, as well as clinical trials that have been conducted with other polo-like kinase inhibitors, gives us reason to believe that PCM-075 can be a first-in-class new treatment option in AML, with a straightforward clinical development plan.

A Phase 1 safety study has already been completed in patients with advanced solid tumor cancers with data indicating an acceptable safety profile and well as anti-tumor activity. This Phase 1 trial was an open-label, dose-escalation of PCM-075, given orally, once daily for 5 consecutive days, within a 21-day cycle, in 19 patients. The median treatment duration was 6 weeks with a median number of two treatment cycles per patient.

The results demonstrate that the on-target activity of PCM-075 indicates favorable evaluation in hematologic malignancies and no relevant off-target or unexpected toxicities were observed. Additionally, the results suggest clinical activity of PCM-075 in solid tumor malignancies as a single agent or in combination therapy.

We submitted an Investigational New Drug (IND) application for a Phase 1b/2 clinical trial of PCM-075 in patients with AML to the FDA on June 27, 2017. On July 24, 2017, the FDA granted authorization for us to proceed with our clinical trial to treat patients with AML.

The Phase 1b/2 is an open-label trial to evaluate the safety and anti-leukemic activity of PCM-075 in combination with decitabine or low-dose cytarabine in subjects with AML. The Phase 1b is a dose escalation trial of PCM-075, in combination, to evaluate drug safety, tolerability, dose and scheduling, and determine a recommended clinical treatment dose for the Phase 2 continuation trial. The initial Phase 1b dose level of 12 mg/m2/day will be increased by 50% increments to reach the maximum clinical dose for AML patients. Pharmacokinetics of PCM-075 and correlative biomarker activity will be assessed prior to the initiation of Phase 2.