SOURCE: Apex Therapeutics, Inc.

Apex Therapeutics, Inc.

April 12, 2016 08:00 ET

ApeX Therapeutics to Present Ability of APX3330 to Target Multiple Oncogenic Transcription Factors in Pancreatic Cancer as Single Agent or Combination Therapy at AACR Annual Meeting

INDIANAPOLIS, IN--(Marketwired - April 12, 2016) - ApeX Therapeutics, a biotechnology company focused on developing novel compounds to treat cancer, today announced three poster presentations describing the ability of drug candidate APX3330 to target multiple oncogenic transcription factors critical to pancreatic cancer cell survival as a single agent or in combination with other known drugs at the American Association for Cancer Research (AACR) Annual Meeting 2016 to be held in New Orleans, LA on April 16-20, 2016.

Pancreatic ductal adenocarcinoma (PDAC) is third leading cause of cancer-related death in the United States and is one of the few cancers for which survival has not improved substantially over nearly 40 years. Pancreatic cancer has the highest mortality rate of all major cancers; 94% of pancreatic cancer patients will die within five years of diagnosis and 74% of patients die within the first year of diagnosis (American Cancer Society: Cancer Facts and Figures 2016). Treatment with chemotherapy has not changed the natural course of this disease, and just recently, with combination of chemotherapeutic agents, the median survival reached a year.

APX3330 is a small molecule that targets the DNA repair protein APE1/Ref-1, a dual function protein involved in both DNA repair and redox-signaling co-activation of oncogenic transcription factors. APE1/Ref-1 regulates multiple transcription factors involved in pancreatic cancer cell survival signaling including HIF-1alfa, AP-1, NFkappaB, and STAT3. High expression levels of APE1/Ref-1 also indicate decreased survival in PDAC as well as other cancers.

Preclinical studies cited in the posters investigated the effects of APX330 as a single agent and in combination with several additional drugs acting through APE1/Ref-1 regulated pathways, including HIF-1alfa, STAT3, and others. Constitutively activated STAT3 has been found to be a key regulator of pancreatic cancer and a target for molecular therapeutic intervention. The addition of APX3330 to STAT3 pathway inhibition via Ruxolitinib (Jak 2 inhibitor) or as a direct STAT3 inhibitor potentiated the killing effect of Ruxolitinib in the tumor, suggesting a rationale for dual targeting strategies for the treatment of pancreatic cancer. In addition, APX3330 combined with a standard dose of Gemcitabine demonstrated significant decreases in tumor volume and cell proliferation compared to treatment by the respective drugs as single-agents, supporting the potential use of this novel combination. Previously published data suggests that synergies between these drugs may mechanistically stem from inter-related cytidine deaminase (Cda) and heme oxygenase 1 (HO-1) response in PDAC cells.

APX3330 has been shown in multiple in vitro and in vivo models of pancreatic cancer to be effective in reducing tumor growth and metastases as a single agent. The safety and dose administration of APX3330 have been established by Eisai pharmaceutical company through a previous development program including toxicology, Phase 1, and Phase 2 clinical evaluation in non-cancer patients in Japan. ApeX Therapeutics is currently developing APX3330 for cancer treatment and a Phase 1 trial is being planned in 2016.

Mark R. Kelley, PhD., Chief Scientific Founder of ApeX Therapeutics and Betty and Earl Herr Chair in Pediatric Oncology, Associate Director of Basic Science Research, IU Simon Cancer Center at Indiana University School of Medicine, commented: "Given the challenges in treating PDAC, we are pleased to share potential opportunities to more effectively target multiple oncogenic transcription factors critical to pancreatic cancer cell survival using novel drug combinations, including APX3330. We believe these synergistic combinations are more likely to yield improved outcomes in this difficult indication."

The following three posters will be presented at the AACR Annual Meeting:

Title: Development of STAT3 dual-targeting strategies for the treatment of pancreatic cancer
Presented by: Melissa L. Fishel, Ph.D., Associate Professor Research, Department of Pediatrics, Indiana University School of Medicine
Date: Monday, April 18, 2016
Time: 8:00 a.m. to 12:00 p.m.
Session Title: PO.ET06.02. Novel Antitumor Agents and Epigenetics
Location: Section 16
Abstract Number: 1246

Title: Targeting Ref-1/APE1 pathway inhibition in pancreatic cancer using APX3330 for clinical trials
Presented by: Dr. Kelley and Fenil Shah, Ph. D., Researcher at Herman B Wells Center for Pediatric Research, Indiana University School of Medicine Indianapolis
Date: Wednesday, April 20, 2016
Time: 8:00 a.m. to 12:00 p.m.
Session Title: PO.ET06.05. HDAC, Methyltransferase Inhibitors, and Novel Anticancer Agents
Location: Section 17
Abstract Number: 4740

Title: Efficacy study of APX3330, a Ref-1 redox inhibitor, and Gemcitabine in a mouse pancreatic ductal adenocarcinoma model
Presented by: Melissa L. Fishel, Ph.D., Associate Professor Research, Department of Pediatrics, Indiana University School of Medicine and Kyle Mcelyea, Indiana University School of Medicine, Indianapolis
Date: Wednesday, April 20, 2016
Time: 8:00 a.m. to 12:00 p.m.
Session Title: PO.TB01.05. Therapeutic Studies in Patient-derived Xenografts
Location: Section 33
Abstract Number: 5183

For more information about the AACR Annual Meeting and to view the poster abstracts, please visit:
http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=63#.VvwuaeIrKM8

About Apex Therapeutics
ApeX Therapeutics is a biotechnology company focused on developing novel compounds to treat cancer targeting the multiple functions of the APE1/Ref-1 protein. Our lead drug candidate, APX3330 targets the treatment of pancreatic cancer and we expect to be in human clinical studies in 2016. To learn more about ApeX Therapeutics, please visit the Company's website at www.apextherapeutics.com

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