Elevation Oncology formed last year with $32.5 million in a Series A financing round led by the initial investor in Loxo Oncology, a company that blazed a trail developing cancer therapies based on genetic signature rather than tumor origin.
On Tuesday the New York-based biotech emerged from stealth aiming to follow in Loxo’s path. It has a Phase 2 trial under way and partnerships with diagnostic companies that it says will give it an advantage in enrolling patients whose cancers have a rare genetic mutation—tumors it hopes to treat with its lead drug candidate.
Elevation founder Shawn Leland (pictured), the company’s chief business officer, saw an opportunity to start a company that would develop drugs to target cancers with a fusion involving the NRG1 gene following a presentation on targeted therapies for lung cancer at the European Society for Medical Oncology annual meeting in 2018. (Leland, who is based in Denver, originally named the company 14ner Oncology, a nod to Colorado’s plethora of 14,000-square-foot-plus mountain peaks, a quarter of which he has summitted.)
The presentation included a case study of a patient with a tumor carrying that mutation who, after treatment with an anti-HER3 antibody, saw 90 percent reduction in tumor volume and a 19-month duration of the therapeutic response—more than the prior four treatments he had received combined, Leland said. Targeting the mutation appeared to interfere with the over-activation of the receptor and slow tumor growth.
“The first person I reached out to was Steve Elms at Aisling Capital,” Leland told Xconomy. Given Aisling’s decision to lead Loxo Oncology’s Series A financing, and Elms’s role with the company as board chairman, “I felt like he was the ideal person to talk to knowing that this was a very similar strategy and path we were looking to pursue in precision oncology.”
Loxo was snapped up last year by Indianapolis pharmaceutical giant Eli Lilly (NYSE: LLY) for about $8 billion; the first Loxo drug to win FDA approval, larotrectinib (Vitrakvi), treats cancers that have a mutation called a TRK fusion. The abnormality is present in 0.5 percent to 1 percent of solid tumors. The year prior San Diego biotech Ignyta, as it was advancing a drug targeting TRK fusions and other mutations, was acquired by Roche for $1.7 billion.
After raising Elevation’s Series A financing in a round led by Aisling, the company acquired an anti-HER3 antibody, seribantumab, from Cambridge, MA-based Merrimack Pharmaceutical (NASDAQ: [[ticker:MACK]]) plus an earlier-stage program. Seribantumab has been tested for safety and tolerability in more than 800 patients, according to Elevation.
Since then Leland said Elevation has generated preclinical research showing that the investigational drug prevents the activation of HER3 signaling in NRG1 fusion models, data that it has submitted for presentation at a medical meeting later this year.
Now the company is starting a Phase 2 study to evaluate seribantumab in patients whose solid tumor cancers have an NRG1 gene fusion and who have exhausted other forms of treatment. The trial, called CRESTONE, is a “basket” study that is designed to test a drug across many cancer types with common genetic profile. (Read more about the rise of such studies in this Xconomy story.) Leland says the mutation is a rare one, appearing in about 0.2 percent of cancers, and that it is working with Ashion Analytics, Strata Oncology, and Tempus to help it find those patients.
Elms is serving as interim CEO of the five-person Elevation team; Lori Kunkel, whose experience includes a stint as acting chief medical officer at Loxo, heads its scientific advisory board. Kunkel says tissue-agnostic drug development involves logistical issues that Elevation’s partnerships with diagnostic companies should help alleviate.
“This is a completely different paradigm from what Big Pharma does, and a lot of people didn’t understand that was why Loxo was successful, because they weren’t following the paradigm—they had to create a lot of new ways of reaching out to patients and testing patients,” she said. “I think that a lot of people … they underestimate how to operationalize this.”
Other companies are also pursuing potential drugs based on genetic signature rather than tumor origin. In May, Lilly won FDA approval for a cancer drug that targets fusions or mutations in the RET gene. Last week Roche and Blueprint Medicines (NASDAQ: [[ticker:BPMC]]) formed a $755 million alliance for the planned commercialization of a cancer drug that also targets the RET gene. An FDA decision for the Blueprint drug is expected by late November.
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