As the field of cancer therapy moves toward precision medicines that address specific genetic signatures, biotech companies are looking for better ways to hit these validated targets. Blueprint Medicines contends a small molecule from Lengo Therapeutics has advantages over two newly approved targeted therapies from two big pharmaceutical giants, and the company has struck a deal to buy the startup and its Phase 1-ready drug.
According to terms announced Monday, Cambridge, Massachusetts-based Blueprint will pay $250 million cash to acquire Lengo and its lead drug candidate, LNG-451. Lengo, based in San Diego, could earn up to $215 million more tied to the achievement of regulatory and sales milestones.
Lengo’s drug is a small molecule designed to block kinases, a type of enzyme, that have mutations known as epidermal growth factor receptor (EGFR) exon 20 insertions. EGFR is a protein involved in cell signaling. In non-small cell lung cancer (NSCLC) and other solid tumors, EGFR mutations can drive tumor growth. While NSCLC is the most common form of lung cancer, EGFR exon 20 insertion mutations are rare, and cancers that exhibit it do not respond to EGFR-targeting drugs.
In May, the FDA approved the first targeted cancer therapy addressing EGFR with an exon 20 insertion mutation. That Johnson & Johnson drug, Rybrevant, is a bispecific antibody that binds to EGFR and MET, another protein expressed on the surface of NSCLC cells. The drug is administered as an infusion. Takeda Pharmaceutical won the regulatory nod in September for its EGFR exon 20-targeting drug, Exkivity, in NSCLC. The small molecule offers patients a dosing advantage, as it’s taken as a once-daily capsule.
In an investor presentation, Blueprint said that all approved and experimental therapies have safety and efficacy limitations, as well as limited ability to reach the central nervous system. Without going into detail, the presentation states that preclinical data for Lengo’s drug showed that LNG-451 blocked all common EGFR exon 20 insertion variants, and it did so without also hitting non-mutated EGFR or other off-target kinases.
Blueprint also said in the presentation that LNG-451 can penetrate into the brain, a feature important for addressing NSCLC that has spread to that organ. The Lengo drug has demonstrated “compelling activity” in a preclinical intracranial disease model, Blueprint said. In the biotech’s view, all of those characteristics give LNG-451 the potential to be the best in the class of drugs that target EGFR exon 20 insertion mutations.
Blueprint’s cancer drug lineup includes Gavreto, a small molecule approved last year as a first-line treatment for NSCLC characterized by alterations to the RET gene. That drug is being commercialized in partnership with Roche. The Blueprint pipeline also includes two drug candidates for NSCLC characterized by EGFR exon 19 deletions as well as a mutant form of EGFR called L858R. The first, BLU-945, is in Phase 1/2 testing; a Phase 1/2 clinical trial for BLU-701 is expected to begin by the end of this year. In the investor presentation, Blueprint said that with the addition of the Lengo drug, the company’s pipeline will address more than 90% of activating EGFR mutations.
Lengo was formed by Frazier Healthcare Partners, which launched the startup last year and backed it with a $15 million Series A round of funding. Frazier said Lengo emerged from discussions within the investment firm and among oncology researchers that identified several cancer mutations that were not well addressed by available cancer therapies. At the time, Lengo kept its cancer targets under wraps but it did disclose a license to novel chemistry licensed from Jubilant Life Sciences Limited, an India-based pharmaceuticals company now known as Jubilant Pharmova.
An investigational new drug application for LNG-451 is being readied for filing with the FDA in December. In addition to that lead drug, Blueprint also gains other undisclosed preclinical cancer therapies, including other kinase inhibitors capable of penetrating into the brain. Lengo also brings the research tools it used to discover them. Blueprint expects to close the Lengo acquisition by the end of this year.
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