Using a stepwise development approach, we leverage early proof-of-concept functional and biomarker data to advance our pipeline of cardiovascular and APOE4-associated Alzheimer’s disease programs.
We retain exclusive worldwide development and commercialization rights to all our product candidates and programs.
LX2006 is a gene therapy candidate designed to deliver a functional frataxin, or FXN, gene for the treatment of FA cardiomyopathy. FA cardiomyopathy is the most common cause of mortality in patients with FA and affects approximately 5,000 patients in the United States.
LX2006 is designed to promote the expression of the protein frataxin to restore normal mitochondrial function and energy production in myocardial cells.. LX2006 is currently being evaluated in an open-label, ascending dose Phase 1/2 clinical trial in patients with FA cardiomyopathy (SUNRISE-FA).
The FDA has granted Rare Pediatric Disease designation and Orphan Drug designation to LX2006 for the treatment of FA.
LX2020 is a gene therapy candidate designed to deliver a fully functional PKP2 gene to cardiac muscle for the treatment of PKP2-ACM. PKP2 mutations are associated with approximately 75% of all genetic cases of ACM, and we estimate they affect approximately 60,000 patients in the United States. PKP2 mutations can cause replacement of heart muscle with fibrotic tissue and fatty deposits, and severe abnormal heart rhythms, or arrhythmias, that cause cardiac dysfunction and can result in sudden cardiac death.
LX2020 is designed to increase desmosomal PKP2 protein levels, reassemble desmosomes and restore myocardial cell function.
LX2021 is a gene therapy candidate we are developing to deliver a functional connexin 43, or Cx43, protein for a group of inherited cardiac muscle disorders associated with a high risk of sudden death, including ACM and certain forms of dilated cardiomyopathy. We believe restoring the Cx43 protein can potentially treat multiple genetic causes of ACM because the cardiac loss of Cx43 is a molecular deficit generally observed in all ACM patient populations.
Our LX2021 program is initially targeting Desmoplakin, or DSP, cardiomyopathy, a distinct form of ACM as well as a certain form of dilated cardiomyopathy, impacting up to approximately 35,000 patients in the United States.
LX2022 is a gene therapy candidate we are developing to deliver a functional TNNI3 gene to myocardial cells to treat a distinct form of hypertrophic cardiomyopathy, or HCM, due to mutations in the TNNI3 gene. Mutations in the TNNI3 gene often result in left ventricular hypertrophy and restrictive cardiomyopathy, leading to arrhythmias and heart failure.
With an estimated prevalence of 1 in 500 people in the United States, HCM is one of the most common forms of genetic cardiomyopathy and is caused by mutations that affect the cardiac sarcomere in approximately 75% of cases
LX1001 is a gene therapy candidate designed to deliver, an APOE2 gene for the treatment of APOE4 homozygous patients with Alzheimer’s disease. Alzheimer’s disease is the leading cause of cognitive decline in late adult life and characterized by complex underlying pathology in the central nervous system, or CNS.
Individuals homozygous for APOE4, an allele of the gene APOE, are approximately 15 times more likely to develop Alzheimer’s disease than the general population, and it is estimated that there are 900,000 APOE4 homozygous patients with Alzheimer’s disease in the United States alone. Conversely, individuals with two copies of the APOE allele APOE2 are 40% less likely to develop Alzheimer’s disease than the general population, which along with other evidence suggest that APOE2 may play a neuroprotective role. LX1001 is designed to express the protective APOE2 gene in the CNS of APOE4 homozygous patients in order to halt or slow the progression of Alzheimer’s disease.
LX1001 is being evaluated in an ongoing open-label, dose- escalation Phase 1/2 clinical trial (LEAD). LX1001 has been granted Fast Track designation by the FDA for the treatment of patients with early Alzheimer’s disease who are APOE4 homozygous to slow disease progression.
LX1021 is a gene therapy candidate we are developing to deliver a Christchurch mutation-modified APOE2 allele for the treatment of APOE4 homozygous patients with Alzheimer’s disease. The Christchurch mutation has been recognized to protect individuals against Alzheimer’s disease even in the presence of significant amyloid pathology. The mechanism of this protection may relate to the fact that APOE, in the presence of the Christchurch mutation, binds poorly to heparan sulfate proteoglycans, which are molecules found on the surface of neurons that may inhibit the spread of tau between cells.
We believe this approach has the potential to enhance the protective effect of APOE2 in homozygous APOE4-associated Alzheimer’s disease.
LX1020 is a gene therapy candidate we are developing to deliver both the protective APOE2 allele and miRNA to suppress APOE4 for the treatment of APOE4 homozygous patients. We believe delivery of APOE2 with concurrent suppression of APOE4 will achieve a higher degree of conversion to the APOE4/E2 heterozygous profile, which should lead to greater therapeutic effect.