Duke Cancer Institute Investigator Discusses Preclinical Activity of ABC294640 in Multiple Myeloma

Preclinical Activity in Multiple Myeloma

Dr. Yubin Kang of Duke Cancer Institute discusses the preclinical activity of the SK-2 inhibitor ABC294640 in multiple myeloma. Dr. Kang has the lead investigator for this investigational drug in early-stage clinical research. They have now entered Phase I/II trial work.

What is ABC294640?

ABC294640 is a first-in-class Sphingosine kinase-2 inhibitor for patients with advanced solid tumors.

In a Phase I trial, investigators found the agent downregulated M01 and cMET. When combined with venetoclax (Venclexta) in preclinical models, it showed great synergistic effect. The investigational drug was picked up in an acquisition when Israel-based RedHill Biopharma acquired it from Apogee Biotechnology Corp.

The Study Results

The open-label, dose escalation Phase Ib/II study evaluating YELIVA® (ABC294640) in multiple myeloma patients who were previously treated with proteasome inhibitors and immunomodulatory drugs is ongoing at Duke University Medical Center.  According to a RedHill press release,  as of Phase Ib portion of the study there have been no dose-limiting toxicities. Although efficacy was not the primary endpoint of the Phase I study, it was observed that out of 10 evaluable subjects, two subjects had stable disease for over four months and one patient achieved a very good partial response (VGPR).

Additionally, preclinical results demonstrated that SK2 is overexpressed in multiple myeloma cell lines and in human multiple myeloma specimens and plays a critical role in myeloma cell growth, proliferation and survival.  Additional preclinical studies described in the abstract demonstrated that treatment with ABC294640 effectively inhibited myeloma tumor growth in vitro and in vivo in mouse xenograft models.

The authors have determined that ABC294640 as a single agent or in combination with B-cell lymphoma 2 (Bcl-2) inhibitor has the potential for treatment of relapsed/refractory multiple myeloma patients that were previously treated with proteasome inhibitors and immunomodulatory agents.

The Phase Ib/II study for multiple myeloma is supported by a $2 million grant from the National Cancer Institute (NCI) Small Business Innovation Research Program (SBIR) awarded to Apogee Biotechnology Corp., in conjunction with Duke University, with additional support provided by RedHIll.

Who is ABC294640 Sponsor?

RedHill Biopharma, established in 2009, is a pharmaceutical company focused primarily on acquisition and development of late clinical-stage new, improved and patented formulations of existing drugs, with preference to a 505(b)(2)* regulatory paths, as well as acquisition and development of late clinical-stage, new and patented orphan drugs.

They went public with an IPO in 2013. They trade under symbol RDHL and have raised a total of $128.2 million based on CrunchBase. By the end of 2018 they had $53 million cash reserves based on their SEC Form 20-F. Redhill commercializes and promotes several gastrointestinal products in the US.  Their key late-stage clinical development programs include 1) Talicia (RHB-105) 2) RHB-104 3) RHB-204 4) (RHIB-102)-BEKINDA®-positive results from Phase 3 study for pulmonary nontuberculous mycobacteria 5) ABC294640(YELVIA®) as well as others.

Comment

The agent is moving toward testing in Phase I/11 trial based on the promising data.  It is related to a “sphingolipid.” It was common wisdom that the lipid only played a structural role however the thinking has changed in the last decade. Presently, it has been suggested that the lipid has a secondary messaging role in which  it also regulated cell signaling.

A recent paper published in Blood argued that approximately 30% of patients with myeloma had upregulation on SK-2.

Lead Research/Investigator

Dr. Yubin Kang, Duke Cancer Institute

See the video and listen to Dr. Kang on Onclive.