Developer gains rights to experimental FA therapies in $21M acquisition deal
Lexeo aims to build 'best-in-class' platform, advance its gene therapy
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Lexeo Therapeutics has acquired the private, clinical-stage company Mantle Therapeutics, gaining the rights to several experimental therapies Mantle had been developing for Friedreich’s ataxia (FA) — including one already in early clinical testing.
In announcing the deal, which could be worth more than $21 million, Lexeo also heralded several new collaborations aimed at further developing LX2006, the company’s own experimental FA gene therapy.
“Our objective is to build the best-in-class therapeutic platform for the treatment of Friedreich ataxia. … Together, these initiatives will strengthen our leadership position in the disease category while supporting disciplined portfolio advancement and capital allocation,” R. Nolan Townsend, Lexeo’s CEO, said in a company press release.
A genetic disease, FA is marked by low levels of frataxin, a protein necessary for the proper function of mitochondria, the so-called powerhouses of cells that make energy. A lack of frataxin leads to problems with cells in many parts of the body, including the brain and heart. Mantle’s pipeline, now owned by Lexeo, boasts four experimental therapies all designed to treat FA.
One treatment candidate, LX3010 (MTL-104), is designed to boost frataxin protein levels and improve mitochondrial health. It works by modulating the activity of HDAC inhibitors and Nrf2, proteins that help control which genes are switched on in cells.
LX3010 is now in early clinical testing, and data from a study of 11 people with FA showed the therapy increased frataxin levels ninefold. According to the developer, this was accompanied by an average improvement of nearly six points on the mFARS, a standard measure of FA severity that usually worsens over time.
Two of Mantel’s other therapies are in preclinical development. One, LX3030 (MTL-707), is similarly designed to increase frataxin levels by targeting proteins that control which genes are active in cells. The other, LX3050 (MTL-501), uses an engineered form of frataxin attached to an antibody fragment. The goal of that treatment candidate is to enhance the delivery of frataxin to the brain.
Mantel’s pipeline also includes LX3070 (MTL-801), a treatment still in the discovery stage. It’s designed to increase frataxin protein levels by stabilizing the messenger RNA (mRNA) of the gene that encodes the protein. mRNA is an intermediary molecule produced when genes are read to make proteins.
Under the terms of the acquisition, Lexeo will pay Mantel’s shareholders $8.3 million upfront, with the potential for an additional $13 million in milestone payments, bringing the deal’s ultimate pricetag to about $21.3 million.
LX2006 leads Lexeo’s FA treatment platform
Still, according to Lexeo, its own experimental treatment, a gene therapy for heart disease in people with FA, “remains the company’s top priority development program.”
LX2006 is designed to deliver a working version of the gene encoding frataxin to cells in the heart. The therapy is designed to be given intravenously, or via infusion into the bloodstream.
To date, the treatment has shown promise in clinical trials in people with FA and a type of heart disease called cardiomyopathy. In the U.S., regulators granted LX2006 breakthrough therapy status, which aims to speed the development of new treatments that could fill unmet needs for serious medical conditions.
Lexeo announced three new collaborations aimed at further developing LX2006. One project, which will be conducted in partnership with Weill Cornell Medicine, is designed to test the effects of administering LX2006 directly into the brain after initial administration into the bloodstream in animal models. This project aims to better understand the potential of gene therapy targeting the cerebellum, a brain region that’s heavily impacted by FA, and to further assess dosing and ways to suppress the immune system’s response.
LX2006 delivers its genetic payload using a viral vector, which is basically a virus that’s been engineered to deliver a therapeutic gene instead of causing infection. Lexeo’s other two new collaborations are option agreements, giving the company the potential to secure exclusive licenses for molecular tools that may improve the utility of LX2006, enable repeat dosing, and provide a more convenient route of administration. Specifically, one agreement covers a novel capsid (viral shell) designed to enable better delivery into the brain and spinal cord, while the other covers a therapy designed to reduce the body’s immune response against the viral vector.
“LX2006 remains our highest priority as the best-in-class treatment for FA cardiomyopathy, and the addition of Mantle’s pipeline, combined with new research collaborations will broaden our technology platform with multiple complementary [brain and spinal cord]-targeted therapeutic strategies designed to restore frataxin in the brain and further improve outcomes for individuals living with FA,” Townsend said.
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