PCM-075 for Acute Myeloid Leukemia (AML)

First of its kind PLK1 inhibitor to enter clinical trials

The Need For New AML Therapies

PCM-075 is an oral, highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine Polo-like Kinase 1 (PLK1) enzyme, which is overexpressed in several different hematologic and solid tumor cancers.

“AML is an aggressive cancer of the blood and bone marrow with approximately 20,000 new cases in the U.S each year.

We see the FDA’s granting of orphan drug designation for PCM-075 as underscoring the medical need for new therapies for patients with AML and an important step forward in our clinical development program.”

Bill Welch, Chief Executive Officer of Trovagene

The Potential Impact of
PCM-075 in AML and Beyond

High PLK1 expression is associated with the most aggressive forms of hematologic and solid tumor cancers. PCM-075 has demonstrated synergy when used in combination with chermothera
peutics and targeted therapies and could potentially enhance the efficacy of current and future standard-of-care therapies.

These combination therapy options present significant market opportunities to address unmet medical needs in other cancers including metastatic Castration-Resistant Prostate Cancer (mCRPC) and beyond.

Phase 1b/2 Clinical Trial in AML

Currently we are conducting our phase 1b/2 clinical trial in AML which is intended to:

Our Pipeline

Explore our pipeline in detail to find out more about the status of our clinical and pre-clinical research programs.

  • Better characterize the safety profile of PCM-075 in AML patients
  • Provide a preliminary assessment of response to PCM-075 when used in combination with standard-of-care chemotherapy
  • Study the effect of different clinical doses and dose scheduling
  • Explore the potential of correlative biomarker analyses to select patients more likely to respond
  • Assess preliminary efficacy of PCM-075 in combination with standard-of-care chemotherapy

The Potential Impact of PCM-075 in AML and Beyond

High PLK1 expression is associated with the most aggressive forms of hematologic and solid tumor cancers. PCM-075 presents an exciting opportunity to be used in combination with chermotherapeutics and targeted therapies and could potentially enhance the efficacy of current and future standard-of-care therapies.

These combination therapy options present significant market opportunities to address unmet medical needs in other cancers including metastatic Castration-Resistant Prostate Cancer (mCRPC) and beyond.

Potentially Synergistic Drugs 1,2
Bortezomib
Cisplatin
Cytarabine
Doxorubicin
Gemcitabine
HDAC Inhibitors
Pacitaxel
Quizartinib (FLT3)
Associated Cancers2
Liquid Tumors:
  • Acute Myeloid Leukemia
  • Acute Lymphocytic Leukemia
  • Non-Hodgkin Leukemia
  • Multiple Myeloma
Solid Tumors:
  • Castration-Resistant Prostate
  • Adrenocortical Carcinoma
  • Triple Negative Breast
  • Sarcomas
  • Small Cell Lung

Evaluation of Efficacy of PCM-075 for MV-4-11 Human Acute Myeloid Leukemia (AML) Xenograft Model in NODSCID Mice

PCM-075 and Quizartinib (FLT3) in AML

  • 30% of AML patients harbor an FLT3 mutation1
  • Midostaurin recently FDA approved,3additional FLT3 inhibitors, including quizartinib, are currently in Phase 3 clinical development2
  • The combination of PCM-075 and quizartinib demonstrated 97% tumor growth inhibition and regression in FLT3 AML xenograft model3

1Kindler et al, Blood 2010, 116:5089-10.

2Stone et al, N Engl J Med 2017, 377:454-64.

3Data on file at Trovagene, Inc.

PCM-075 and Abiraterone (Zytiga)® in mCRPC

25,000 men progress to metastatic prostate cancer resistant to standard androgen-deprivation therapy annually. Current therapies include abiraterone, enzalutamide and docetaxel. However, patients develop resistance to abiraterone and enzalutamide generally within 9-15 months and do not respond well to subsequent therapies.

PCM-075 in combination with abiraterone may prolong the response to anti-androgen therapy allowing for more effective mCRPC combination therapies.

  • PCM-075 plus abiraterone suggested increased sensitivity when compared to abiraterone alone, showing decreased viability of mCRPC tumor cells1
  • Combination appears to enhance the PCM-075 mechanism of action of arresting cells during mitosis1
  • There continues to be a large medical need to extend the benefit of response to abiraterone in mCRPC

1Yaffe, Michael, MD and Trovagene, 2017

C4-2 Castration-Resistant Prostate Cancer Cells Increased Sensitivity to Abiraterone in the Presence of PCM-075