Roswell Park to Present Findings on Jasco Pharmaceuticals’ Novel PIM Inhibitor at AACR 2014

Latest studies strengthen evidence on JP_11646 as effective treatment for pancreatic, bladder and blood cancers

Released: 4-Apr-2014 5:00 PM EDT
Source Newsroom: Roswell Park Cancer Institute
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Citations AACR Annual Meeting 2014

Newswise — BUFFALO, N.Y. — The American Association for Cancer Research (AACR) Annual Meeting 2014, which starts tomorrow, will provide researchers from Roswell Park Cancer Institute (RPCI) and Jasco Pharmaceuticals LLC an opportunity to update colleagues from around the world on their latest collaborative efforts in the area of drug development.

Since spring 2013, Woburn, Mass.-based Jasco has been working with the Center for Drug Development at RPCI to advance development of Jasco’s lead agent, JP_11646, to the clinical-trial phase. The agent is a novel PIM inhibitor that targets a key class of kinase enzymes that help to regulate cancer cell survival.

Three RPCI investigators will present findings from recent studies of Jasco’s promising investigational agent at the AACR Annual Meeting 2014, to be held April 5-9, 2014, at the San Diego Convention Center, San Diego, Calif.

“We knew from our earlier preclinical work that JP_11646 had shown great promise for treating a wide variety of cancers, particularly multiple myeloma,” says Jasco CEO Eugene Baldino. “These AACR 2014 abstracts provide further evidence that JP_11646 may be a promising option for treating pancreatic cancer, and also allowed us to expand our studies to include bladder cancer and acute leukemias.”

“Taken together, these findings represent tremendous positive momentum for the translational development of JP_11646 from bench to bedside,” says Gerald Fetterly Jr., PhD, Director of RPCI’s Pharmacokinetic/Pharmacodynamic Core Facility and an Associate Professor of Oncology within the departments of Medicine and Pharmaceutical Sciences.

“We are encouraged by the favorable response in all three of these studies, and based on this evidence expect to move quickly with further preclinical work as well as our first testing of this agent in clinical studies,” added Baldino.

Details of the three studies, including presentation times and locations, follow.

Yi Ding, PhD, a postdoctoral affiliate in RPCI’s Department of Medicine, is first author on “Preclinical efficacy of the novel PIM inhibitor, JP_11646, in pancreatic cancer” (abstract 751), to be presented Sunday, April 6, from 1 p.m. to 5 p.m. in Hall A-E, Poster Section 31.

There is an unmet need for new and better treatments for pancreatic cancer, which is often diagnosed at late stages, and with poor prognosis. Based on recent studies showing the effects of JP_11646 on pancreatic cancer cell growth, Ding and colleagues sought to further evaluate the antitumor activity of JP_11646, both as a single agent and in combination with chemotherapy in cells and animal models of pancreatic cancer. They found significant tumor growth inhibition by JP_11646 alone and an even greater inhibition when JP_11646 was combined with gemcitabine. The preclinical findings suggest that JP_11646 could be a promising treatment for pancreatic cancer and that the findings merit follow-up in the clinical setting.

Wei Luo, MD, PhD, a Translational Research Scientist in RPCI’s Department of Pharmacology and Therapeutics, is first author on “Targeting PIM1 kinase enhances 1,25-dihydroxyvitamin D3-mediated anti-tumor activity in bladder cancer cells” (abstract 607), to be presented Sunday, April 6, from 1 p.m. to 5 p.m. in Hall A-E, Poster Section 26.

The most active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25D3), has shown preclinical antitumor activities and the ability to enhance the effects of common chemotherapeutic drugs in a broad range of cancers, including bladder cancer. PIM1 kinase regulates an enzyme that breaks down 1,25D3; this relationship between PIM1 and the enzyme in bladder cancer cells was observed previously by Luo and colleagues.
In this study, the team set out to determine whether blocking PIM1 activity would indirectly enhance the antitumor effects of 1,25D3. Using a small molecule inhibitor JP_11646 to inhibit PIM1 activity, they demonstrated a significant inhibition in bladder cancer cell growth. When combined with 1,25D3, the inhibition of PIM1 activity by JP_11646 enhanced the effects of 1,25D3 on suppressing bladder cancer cell growth. This is the first study to indicate that blocking PIM1 activity is a potential approach for enhancing the effects of vitamin D therapy in bladder cancer.

Krista E. Pundt, a pre-doctoral trainee in RPCI’s Department of Molecular Pharmacology & Cancer Therapeutics, is first author on “Preclinical efficacy of the novel PIM2 kinase inhibitor, JP_11646, in human acute leukemia models” (abstract 5459), to be presented Wednesday, April 9, from 8 a.m. to noon in Hall A-E, Poster Section 31.

PIM kinases have been implicated in tumor survival and development, and are found in abundance, preferentially, in blood-related malignancies. In this study, Pundt and colleagues aimed to investigate the effects of JP_11646 in blocking PIM kinase activity in human acute myeloid (AML), acute lymphocytic leukemia (ALL) and lymphoma cell lines. Their findings showed that JP_11646 is highly potent and achieves broad antitumor activity by triggering cell death across a wide range of human ALL and AML cell lines. Further investigation in animal models of AML is underway to confirm these findings, which would provide insights for a novel therapeutic approach in patients with the disease.

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About Jasco:
Jasco Pharmaceuticals LLC is a privately held, pre-clinical stage biopharmaceutical company focused on the development of small molecule oncology therapeutics. Jasco was founded with a core expertise in high speed medicinal chemistry providing a launching point for a chemical genomics approach to the discovery of selective protein kinase inhibitors. The company’s vision is to rapidly and effectively develop pre-clinical oncology candidates that are progressed through the clinical development process by means of strategic partnerships. For more information, please visit www.jascopharma.com or call Carmen M. Baldino, Ph.D., at 339-227-6822 Ext. 12.

About RPCI:
The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org. Follow Roswell Park on Facebook and Twitter.

Editor’s note: To arrange an interview with RPCI presenters and expert sources, please contact Annie Deck-Miller at annie.deck-miller@roswellpark.org, mobile 716-602-5817, or Tara Yates, who will be onsite at the meeting, at tara.yates@roswellpark.org, mobile 716-961-8367.


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