Following two recent accomplishments – the FDA's acceptance of its investigational new drug application for lead drug ABC294640 and orphan drug status awarded in pancreatic cancer – Apogee Biotechnology Corp. has emerged from stealth mode and is looking to start clinical testing next year with its sphingosine kinase inhibitor.
"It's an exciting time for us because we've got a lot of preclinical data and now it's time to find out if it will work in humans," said President and CEO Charles D. Smith, who founded Apogee in 2001 as a spinout of Penn State University.
While perhaps not a newco in the strictest sense of the word, the firm spent its early years establishing the sphingolipid technology. Then it continued flying under the radar. "We were focused on the science and then we were hyperfocused on the IND package," Smith told BioWorld Today.
Apogee submitted the IND earlier this year. In September, the FDA gave the go-ahead for a Phase I trial of ABC294640 that will test the drug in two stages: a dose-escalation portion expected to enroll patients with any type of advanced solid tumors and an expansion portion that will involve pancreatic cancer patients.
The study is slated to start in January and should take an estimated 12 months to 18 months to complete. In addition to the usual safety parameters, Apogee also is hoping the trial will yield pharmacodynamic data, specifically measuring levels of sphingosine-1 phosphate as a biomarker.
S1K is produced by the sphingosine kinase, an oncogene expressed in a variety of tumors, and helps cancer cells avoid apoptosis.
In fact, while screening the sphingosine kinase target at Penn State, Smith discovered its critical link between cancer cell proliferation and cancer cell apoptosis. In other words, he said, "it's sitting at the switch of life and death for the tumor cells."
S1K also has implications in other disease processes such as inflammation. Cytokines such as TNF-α required signaling through that same pathway. Plus, cancer is believed to have an inflammatory component as well.
"So it's really a multitarget [approach]," Smith said. Inhibiting S1K goes after "not just the signaling pathway but the other processes that support tumor growth."
Based on promising preclinical data, Apogee envisions ABC294640 as part of combination therapy. Pancreatic mouse xenograft models have shown efficacy when combined with gemcitabine, the current standard of care, as well as with taxanes, which are getting more attention in the pancreatic cancer space thanks to early clinical success by Celgene Corp.'s Abraxane (nab-paclitaxel).
If early data pan out in cancer, Apogee plans to use those results for filing INDs in other indications.
"It's really a platform technology," Smith said. The broad applications could make it an attractive partnering asset, and the firm is exploring a number of options. But even if it inks a collaboration, "we'd like to be involved, at least through Phase II," he added.
Apogee has taken advantage of the sphingolipid technology's broad potential to obtain funding. Since its incorporation, the company has relied almost entirely on Small Business Innovation Research grants, including a grant from the National Eye Institute to evaluate the technology in retinopathy and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases in inflammatory bowel disease. Apogee also is working with the SENS (Strategies for Engineered Negligible Senescence) Foundation in the area of regenerative medicine.
To date, the company has raised about $8 million in SBIR funding. It's also gotten some state tax credit funding from Pennsylvania and recently received $825,000 from the Qualifying Therapeutic Discovery Project Program.
Apogee is headquartered at the Hershey Center for Applied Research in Hershey, Penn.