A joint venture between biotech stalwart Ohr Pharmaceutical and Cold Spring Harbor Laboratory is taking the fight to breast cancer – though a revolutionary treatment may still be a half-decade away at least.
Cold Spring Harbor-based DepYMed, which incorporated just 10 months ago, is eyeing the first clinical trials of an enzyme inhibitor the company is proffering as a potential breakthrough for patients with HER2-positive breast cancer – a cancer that causes uncontrolled amplification in the human epidermal growth factor receptor 2, a gene that produces pivotal protein cells.
Based on research by Dr. Nicholas Tonks, deputy director of the CSHL Cancer Center, DepYmed announced in May 2014 the validation of Trodusquemine – an inhibitor of the critical protein tyrosine phosphatase 1B (PTP1B) enzyme – as a therapeutic candidate for HER2-positive breast cancer. Now the company is working with the North Shore-LIJ Health System to schedule its first clinical trials of Trodusquemine on breast cancer patients.
Former Pfizer and Forest Laboratories executive Andreas Grill, who was named DepYmed CEO in January, said Phase 1 clinical trials involving roughly 25 patients would likely begin this spring. Though “not statistically significant,” Phase 1 – lasting on the order of nine months – will help researchers identify a “maximum tolerable dose” of the enzyme inhibitor, he said.
“It’s a probability study that allows you to determine how high a dose cancer patients can take,” Grill told Innovate-LI. “Then you start designing your efficacy trials around the maximum tolerable dose.”
That’s Phase 2, a larger pilot study involving some 100 patients and running about two years. If all goes well, a successful Phase 2 leads to a meeting with the FDA to establish the parameters of a Phase 3 trial, the “pivotal clinical trial” that will involve as many as 300 cancer patients, Grill noted.
A best-case scenario, the CEO added, is the launch of a commercial product early in 2021, with Trodusquemine – DepYmed is yet to create a snappy commercial name – serving as a polytherapy alongside other breast cancer medications.
“There are a number of products out there for patients with HER2-positive breast cancer, such as Herceptin,” Grill said. “Ultimately, we’d like to see our product used as a monotherapy – that’s the dream endgame – but the likelihood is it will be a polytherapy in some kind of synergistic drug combination.”
Cynthia Hahn, chief operating officer for research at North Shore-LIJ’s Feinstein Institute for Medical Research, said the health system greenlighted the Phase 1 trials after DepYmed approached North Shore-LIJ officials and the two parties engaged in a series of discussions.
“We had to determine if we had the expertise, the resources and the patient population to conduct the trial,” Hahn noted. “We discussed it with them and decided to move forward.”
While committed to the Phase 1 trials, Hahn stressed that neither the Feinstein Institute nor DepYmed is yet committed to conducting further phases at North Shore-LIJ, assuming the Phase 1 trials go well.
“It’s a wait-and-see thing,” she said. “From DepYmed’s perspective, they have to determine if the institute was able to deliver – did we have the expertise and the right patient population? We also have to determine if it was the right therapeutic process for our patients. They might decide not to move forward, and we might also.
“This does seem to be a good fit for us,” Hahn added. “As an organization, we see clinical trials like this as a good opportunity to bring innovative cancer treatments to the Long Island community.”
Wherever the subsequent phases are conducted, bringing Trodusquemine to market as a breast cancer treatment will be a long road, but Grill understands the route better than most. The longtime Pfizer researcher nurtured a number of companies as leader of Forest Laboratories’ Global Project Development Team and a member of several of the labs’ Joint Steering and Development committees, making him responsible for everything from product conception to marketing.
He’s also served as Stony Brook University’s bioentrepreneur in residence, advising other entrepreneurs on the development of various startup technologies.
While Ohr Pharma technically owns Trodusquemine – one of a number of PTP1B inhibitors in the firm’s stable – Grill’s project leadership, the baseline work done by Tonks’ CSHL oncology team and North Shore-LIJ’s participation in the Phase 1 trials make this “very much a Long Island story,” noted Teri Willey, CSHL’s head of technology transfer.
“It’s very early,” Willey said. “But it’s a great example of us partnering with two other important New York institutions – DepYmed, which is very small, and North Shore-LIJ, which is obviously a really important institution on Long Island.”