RARE Daily

Lexeo Therapeutics Launches with $85 Million to Develop Gene Therapies for Monogenic Diseases

January 7, 2021

Rare Daily Staff

The newest addition to the gene therapy space, Lexeo launched with $85 million focused on gene therapies for rare and non-rare monogenic diseases.

Longitude Capital and Omega Funds led the oversubscribed series A financing, with participation from Lundbeckfonden Ventures, PBM Capital, Janus Henderson Investors, Invus, Woodline Partners, the Alzheimer’s Drug Discovery Foundationi, and Alexandria Venture Investments.

Lexeo was put together by rare disease and gene therapy industry veterans Steven Altschuler, former chairman of Spark Therapeutics, CEO R. Nolan Townsend, former North America regional head of rare disease at Pfizer, Chief Medical Officer Jay Barth, former chief medical officer at Amicus Therapeutics, and gene therapy pioneer Ronald Crystal, professor and chairman of Weill Cornell’s Department of Genetic Medicine and director of the Belfer Gene Therapy Core Facility who has more than 30 years of experience with adenovirus and adeno-associated virus vectors.

“Lexeo’s AAV-mediated gene therapy programs have the potential for broad applicability across a range of therapeutic indications, and in a single company pipeline present an opportunity for the natural evolution of gene therapy from rare genetic conditions to more common diseases,” said Crystal.

Lexeo’s pipeline includes three clinical-stage AAV-mediated gene therapy programs in monogenic diseases and up to 15 potential additional AAV gene therapy programs in monogenic and acquired diseases primarily developed at Weill Cornell Medicine.

The company will use the proceeds from the financing to advance its three lead experimental programs: LX2006, an IV-administered therapy for cardiomyopathy associated with Friedreich’s ataxia; LX1004, a CNS-administered therapy for CLN2 Batten disease; and LX1001, a CNS-administered therapy for APOE4-associated Alzheimer’s disease.

Friedreich’s ataxia (FA) is a rare, inherited degenerative multi-system disorder caused by a gene mutation that disrupts the normal production of the protein frataxin, critical to the function of mitochondria (the energy producing factories) in a cell. Usually beginning in childhood, it leads to impaired muscle coordination that worsens over time, typically progressing to serious heart conditions, including hypertrophic cardiomyopathy and arrythmias. FA is also associated with vision impairment, hearing loss, scoliosis, diabetes and slurred speech. Friedreich’s ataxia can shorten life expectancy, with heart failure the most common cause of death.

Supported by de novo, soon to be published pre-clinical research, LX2006 is an IV-administered AAV-mediated frataxin gene therapy treatment focused on the cardiac pathology of FA. Lexeo is completing IND-enabling pre-clinical studies and expects to initiate a phase 1 trial in 2021.

CLN2 disease (late infantile Batten disease) is an autosomal recessive lysosomal storage disease with typical onset in children between 2 and 4 years of age. The disease is caused by mutations in the CLN2 gene, resulting in progressive cognitive impairment, visual failure, seizures, and deteriorating motor development.

LX1004 is an AAV-meditated gene therapy treatment delivering CLN2 to the central nervous system. In December 2020, clinical data published in Science Translational Medicine found a single administration of AAV-mediated CLN2 gene therapy (LX1004) slowed the progression of CLN2 disease in children. Treatment with LX1004 was well tolerated, with minimal serious adverse events in the acute/post-operative period and over the 18-month study period. With this phase 1/2 study complete, the company plans to advance the program into a pivotal study in 2022.

Alzheimer’s disease is the leading cause of late-onset dementia, characterized by progressive memory loss and cognitive decline in humans. APOE is a major cholesterol transporter and is in part linked to the pathogenesis of Alzheimer’s disease due to development of amyloid plaques and tau-tangles in the brain. People who inherit APOE4 alleles are at significantly higher risk for developing Alzheimer’s disease and at an earlier age of onset than people who inherit APOE3 or APOE2 alleles, which have normal and reduced risk of disease onset, respectively.

LX1001 is an AAV-mediated gene therapy treatment delivering APOE2 to the central nervous system of people with two APOE4 alleles (homozygotes), via a CNS route of administration. A phase 1 clinical study is ongoing.


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