Armed with $68 million in Series B funding, Epicrispr Biotechnologies (Epic) is initiating human trials of its lead candidate EPI-321, an epigenetic therapy for the neuromuscular disorder, facioscapulohumeral muscular dystrophy (FSHD). The study, which is expected to begin this year, will evaluate the safety, tolerability, pharmacodynamics, and biological activity of a single dose of the treatment in adults with FSHD.
The financing was led by Ally Bridge Group, with participation from SOLVE FSHD, the venture philanthropy organization founded by Chip Wilson, founder of Lululemon Atheletica and FSHD patient, along with other new and existing investors. Epic plans to use the money to test its epigenetic modulator therapy in nine patients in New Zealand as well as to continue advancing its pipeline of epigenetic therapies.
Epic also said that it is working with Richard Roxburgh, MBChB, PhD, an associate professor of medicine at the University of Auckland, who will be the principal investigator for the EPI-321 clinical trial. The study will be conducted in partnership with Pacific Clinical Research Network, a clinical research center in New Zealand. EPI-321 is a one-time gene-modulating therapy designed to silence aberrant expression of DUX4, a gene that is incorrectly activated in FSHD and leads to progressive muscle degeneration. The therapy is delivered to patients using a clinically validated adeno-associated viral vector.
Amber Salzman, PhD, Epic’s CEO, told GEN that patients will be dosed one at a time in monthly intervals—the second patient will be dosed a month after the first one. “We’ll be doing muscle biopsies at baseline and we’ll also be doing it at three months and then 12 months,” she explained. “What we hope to see between baseline and three months is that we did in fact methylate that hypomethylated region.” They will assess whether that methylation translates to suppressing DUX4 by looking at downstream markers of the gene. At the six- and twelve-month marks, they will assess functional measures such as muscle strength and gait.
Preclinical tests of the treatment were very promising and Epic is optimistic about EPI-321’s chances in patients. Data from these studies, which used myocyte cultures from different patients as well as mouse xenograft models, showed that EPI-321 had robust and durable suppression of DUX4 expression and protection of muscle tissue. Based on these results, “we feel really good about the translatability,” Salzman told GEN.
Founded in 2019, Epic’s technology is built on CRISPR-based discoveries from Lei Stanley Qi, PhD, a Stanford University bioengineer and named co-inventor on the CRISPR patent held by the University of California. Its platform, dubbed the Gene Expression Modulation System (GEMS) platform, is designed to tune gene expression without altering the underlying DNA. Epic uses GEMS to design guide RNAs for target genes from a library of different types of modulators including histone modulators and transcriptional activators and repressors. Besides EPI-321, Epic has four research-phase programs targeting conditions like retinitis pigmentosa and familial hypercholesterolemia.
If EPI-321 succeeds in clinical trials, it would be a boon for people with FSHD. Symptoms of the disease start in the teens to early twenties. About 20% of cases are pediatric patients, who usually die at a very young age due to respiratory failure. Symptoms in older patients include weakness of the abdominal muscles, face, hip, and limbs as well as joint and spinal abnormalities.
Salzman has family who either currently have the disease or have passed away from it. For people like her and SOLVE FSHD’s Wilson, who lives with the disease, this fight is a very personal one and they are working to drum up interest and, hopefully, additional investments in novel therapies that could improve outcomes for FSHD patients. “I think [the word] is starting to get out there,” Salzman said. In fact, in the last year alone ”there have been three big pharma deals” focused on neuromuscular indications.
Specifically, in May 2024, Sanofi and Fulcrum Therapeutics signed an agreement to develop and commercialize losmapimod, an oral small molecule being investigated for the treatment of FSHD. Under the terms of the agreement, Fulcrum received an upfront payment of $80 million and was eligible to receive an additional $975 million based on certain milestones and royalties.
Then in November last year, Novartis acquired Kate Therapeutics as part of its efforts to develop gene therapies for patients. Kate Therapeutics’ primary programs include preclinical candidates for Duchenne muscular dystrophy, FSHD, and myotonic dystrophy type 1 (DM1). That transaction was valued at up to $1 billion. Lastly, Sarepta Therapeutics announced a deal with Arrowhead Pharmaceuticals that allowed Sarepta to license several clinical and preclinical programs including treatments for DM1 And FSHD.
This broader interest in neuromuscular disorders bodes well for Epic as it moves forward in what is a tough market for gene therapies with some companies restructuring their pipelines or filing for bankruptcy. Salzman told GEN that her company has worked hard to be “incredibly capital efficient” only raising the funds they need to meet key milestones and by maintaining a relatively low headcount. As a result, they have needed to raise a fraction of the funds raised by some other companies in the space, she said. Also, “having an incredible team who’s very good at what we do … has enabled us to move so well in such a challenging market.”
