Drugs from a class called tyrosine kinase inhibitors have become standard treatments for some cancers, but the improved survival of patients taking these medicines introduces a new problem. As patients live longer, many decide they no longer want to live with the side effects, so they try switching to more tolerable therapies. Enliven Therapeutics is developing new tyrosine kinase inhibitors with potentially better side effect profiles. It has swung a deal that infuses it with nearly $247 million to develop its pipeline, including a lead program already in the clinic.

Boulder, Colorado-based Enliven is joining the public markets through a reverse merger with Imara, a rare disease drug developer whose stock price plummeted following twin clinical trial failures earlier this year. Under the all-stock deal announced late last week, Imara will issue shares to Enliven stockholders, who will own about 84% of the combined company while Imara’s shareholders will own about 16%. The combined company will carry the Enliven name and it will be run by that company’s management team.

Tyrosine kinases are enzymes that play a role in many cellular functions, but genetic mutations can lead to overactive enzymes that drives cancer growth. The most advanced Enliven drug candidate is ELVN-001, an experimental treatment for chronic myeloid leukemia (CML). The Enliven drug targets a tyrosine kinase called BCR-ABL. Speaking during an Oct. 13 conference call, Enliven CEO Sam Kintz said that while currently available kinase inhibitors addressing BCR-ABL enable patients to live for decades, they aren’t sufficiently selective to that target, which leads to side effects and tolerability issues. He added that about 20% of patients switch therapy within the first year and about 40% of patients switch within the first five years.

“We believe that as the CML market continues to develop, delineation between lines of therapy will become much more blurred,” Kintz said. “The chronic nature of the disease allows doctors and patients to freely switch between options, trying to find the right drug that works best for each specific patient. Additionally, similar to the HIV market, we believe that tolerability and convenience factors, along with improved efficacy, will drive adoption even in earlier lines of therapy, and even with multiple generic options.”

Enliven describes its drug as highly selective to its target. A Phase 1 trial is enrolling adults whose CML has relapsed or has not responded to treatment with tyrosine kinase inhibitors, as well as those who can’t tolerate the drugs from this class that are currently available. Preliminary data from this study are expected by the end of 2023.

A second lead program, ELVN-002, targets a tyrosine kinase receptor called HER2 and its mutants. Enliven is initially focused on developing this drug as a second-line treatment for HER2 mutant non-small cell lung cancer (NSCLC). Enhertu, an HER2-targeting cancer drug from AstraZeneca and Daiichi Sankyo, won an additional FDA approval in August for this type of lung cancer following its landmark approval in breast cancer. But Kintz said there’s an opportunity for Enliven’s drug to treat patients who are intolerant of Enhertu. The company plans to submit an investigational new drug application for its HER2-targeting drug later this quarter.

Enliven plans to nominate its third product candidate in the first half of next year. According to an investor presentation, that drug will be chosen from among three discovery-stage programs that address undisclosed targets in solid tumors as well as one program that can penetrate the central nervous system.

Some top-tier investment firms have bought into Enliven’s strategy. Concurrent with the merger with Imara, Enliven plans to raise $165 million in a private financing co-led by Fairmount and Venrock. Other investors participating include Fidelity Management & Research Company, RA Capital Management, Frazier Life Sciences and Commodore Capital. Imara brings $82.3 million to Enliven, which together with the new financing and Enliven’s cash reserves, will bring the combined company’s cash balance to about $300 million. Enliven expects the cash will support the company into early 2026.

Enliven started in 2019, backed by seed financing from OrbiMed and 5AM Ventures. The biotech had raised more than $140 million, most recently an $85 million Series B financing last December co-led by Cormorant Asset Management and Surveyor Capital.

The tyrosine kinase inhibitor space has been active this past year. In June, Bristol Myers Squibb agreed to pay $4.1 billion to acquire Turning Point Therapeutics, a biotech whose lead drug is on track for an FDA submission in lung cancer. In August, Novartis won European Commission approval of its drug Scemblix for CML. The FDA approved the small molecule last year. Theseus Pharmaceuticals is developing tyrosine kinase inhibitors that overcome drug resistance due to mutations. Earlier this month, the biotech nominated a development candidate for NSCLC; an investigational new drug application is being planned for the first half of 2023.

The reverse merger agreement brings to a close Imara’s pursuit of “strategic options.” The Boston company’s lead drug candidate, tovinontrine, failed mid-stage clinical trials in April in the rare blood disorders sickle cell disease and beta thalassemia. In September, Imara reached a $35 million deal to sell the asset to Cardurion Pharmaceuticals. If Cardurion is able to make something of the small molecule, Imara shareholders could receive up to $60 million in milestone payments.

When the reverse merger closes, Imara CEO Rahul Ballal will stay on as a member of the Enliven board of directors. Enliven aims to complete the merger and financing in the first quarter of next year. The company expects its shares will trade on the Nasdaq under the stock symbol “ELVN.”

Photo by Flickr user Lengyal Mark via a Creative Commons license