Genomic Testing + Proven mAb = Precision Oncology Medicine

By Matthew Pillar, Editor, Bioprocess Online

Back in May 2021, I had the good fortune to meet and interview Dr. Greg Dewey, president at Albany College of Pharmacy and Health Sciences (ACPHS). We talked at length about the lack of Pharm.D. graduates in biopharmaceutical careers, and the work ACPHS is doing in collaboration with BeiGene, and the FDA to change that reality.

A few months later, I met an ACPHS Pharm.D. graduate who could serve as the poster child for Dr. Dewey’s efforts. Like many Pharm.D. graduates, after earning his Doctorate degree and RPh license, Shawn Leland did a little teaching (at Rutgers’ Ernesto Mario School of Pharmacy). Like most of them, he also took a job in retail pharmacy. He wasn’t long for it. Dr. Leland told me his story, and how it led him into precision medicine, on episode 75 of the Business of Biotech podcast.

During his last year at pharmacy school, Dr. Leland’s first clerkship rotation found him doing oncology and infectious disease research at Roswell Park Cancer Institute in Buffalo, NY. That experience, he says, showed him that a Pharm.D. doesn’t limit its holder to treating patients with standard of care therapies. “It can be about exposing them to research and clinical trials, being a part of the innovation, and advancing the fields of medicine that are moving the fastest,” he says. That early, focused inspiration led Leland to industry. He interned with Pfizer, did a post-doctoral fellowship with Bristol-Myers Squibb Oncology Medical Affairs, and then moved on to oncology R&D with Eli Lilly and Company. That led to business development leadership positions at ARIAD Pharmaceuticals, Argos Therapeutics, and Verastem Oncology before Dr. Leland took the leap and founded his own biopharma startup, Elevation Oncology, in 2019.

The Impetus Behind A Biopharma Startup

In late 2018, Dr. Leland was in Munich attending a presentation on targeted therapies in lung cancer by renowned Memorial Sloan Kettering oncology physician Alex Drilon, M.D. One of Dr. Drilon’s slides, describing a target called neuregulin (NRG), caught Dr. Leland’s eye. “I knew nothing about the target, but was intrigued by some of its unique biological features and the fact that it had been identified in multiple types of cancer,” he says. “Its genomic markers carry the hallmark of being a true oncogenic driver that’s predominantly mutually exclusive of other known oncogenic driver targets,” says Leland. “If we could identify with genomic testing that this was the one and only thing driving tumor growth and proliferation, it should ideally be amenable to a targeted monotherapy approach,” he says.

During the presentation, Dr. Drilon highlighted a case study demonstrating that the target could be drugged using existing monoclonal antibodies developed for broad patient populations with diverse types of cancer. Dr. Leland anticipated that genomic testing to detect the presence of NRG1 gene fusion would increase the probability of clinical trial success in patients with that biomarker. That’s the premise on which Elevation was founded. He developed a pitch deck, hit the road, and on July 12, 2019, Elevation closed a $30 million Series A financing round. That very afternoon, Elevation closed an asset purchase agreement with Merrimack Pharmaceuticals to acquire its oncology asset Seribantumab.

That’s what the company is now developing for patients with solid tumors demonstrating NRG1 gene fusions. It’s partnered with a host of next-generation sequencing and diagnostics providers to zero in on patients with NRG1 fusion biomarkers for its Phase 2 CRESTONE study.

A Different Perspective On Drug Development

To rationalize precision medicine in small patient population with a rare genetic alteration, Dr. Leland says you must change your perspective on drug development from the outset. He points to three key areas of differentiation: Regulatory strategy, strategic partnerships, and clinical approach.

“You can't just do drug development the same way every other company has done drug development in the past,” says Dr. Leland. “You need to pay close attention to changes in the regulatory landscape to understand how the FDA and other regulatory agencies are contributing to more expedited development paths and strategies to cater to rare, genomically-defined patient populations.”

You also need to accept partnership and collaboration. “To make something commercially attractive, or attractive from a business standpoint in a rare genomically-defined patient population, you have to partner and collaborate with diagnostic, pharmaceutical, and biotech companies and patient advocacy groups to find these patients,” says Dr. Leland. The notion of being able to do it by yourself, he says, is not the way forward for precision medicine.

Flexible and broad clinical trials, says Dr. Leland, contribute to finding a profitable path forward. “Developing for one type of cancer might not lead to a profitable path through the clinic,” he says. “If I can develop in all types of cancers and do one clinical trial in a tumor agnostic environment that’s focused on patients with a specific genomically-defined alteration, then I can pursue a broad indication with regulatory agencies bases on one clinical trial,” he says. To date, four FDA-approved therapies have followed the tumor agnostic development path among genomically-defined patient populations. While it’s cutting edge, the precedent is set.

Learn much more about Elevation’s precision approach to seribantumab on episode 75 of the Business of Biotech.