Another milestone for in vivo gene editing! YolTech Therapeutics' YOLT-202 receives FDA RMAT designation | Unity Ventures Portfolio
A promising "one-and-done" curative treatment for alpha-1 antitrypsin deficiency that could become the best-in-class therapy globally
Unity Ventures portfolio company YolTech Therapeutics recently announced that its investigational in vivo gene editing therapeutic YOLT-202 has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for the treatment of alpha-1 antitrypsin deficiency (AATD).
The RMAT designation is designed to facilitate the development and review of regenerative medicine therapies for serious or life-threatening diseases that have the potential to address significant unmet medical needs. Upon receiving this designation, qualifying programs may access corresponding regulatory support from the FDA during development and review.
AATD is a genetic disorder caused by mutations in the SERPINA1 gene, resulting in significantly reduced plasma AAT levels and predisposing patients to chronic obstructive pulmonary disease and liver damage. The most common deficiency alleles are Z (Glu342Lys) and S (Glu264Val), with the Z allele causing misfolding and polymerization of the AAT protein; over 95% of severe patients have the PiZZ genotype.
YOLT-202 is based on YolTech's self-developed next-generation adenine base editor YolBE, which enables efficient and precise gene correction at the SERPINA1 PiZ site, converting the high-risk pathogenic PiZ mutation to normal PiM, thereby restoring functional AAT protein expression in hepatocytes. This approach achieves precise targeted editing while avoiding bystander editing of surrounding bases, offering a novel therapeutic pathway for AATD.
Previously, YOLT-202's Investigational New Drug (IND) application was approved by the FDA to initiate an open-label, single-dose escalation phase 2/3 clinical study to evaluate its efficacy and safety in adult AATD patients. The study is designed as a multi-regional clinical trial (MRCT). Additionally, YOLT-202 has received FDA Orphan Drug Designation (ODD).
YOLT-202 is also currently being evaluated in a first-in-human investigator-initiated trial (IIT) (NCT07193615) to assess its safety, tolerability, and preliminary efficacy. Preliminary clinical data show rapid, dose-dependent increases in functional AAT levels in subjects, with AAT levels reaching the normal range in some high-dose subjects. These findings suggest that YOLT-202 has the potential to become a "one-and-done" and globally best-in-class innovative treatment for AATD.
YolTech Therapeutics has developed a portfolio of gene editors and LNP delivery systems with global independent intellectual property rights, with six programs in clinical stages, making it the company with the most in vivo gene editing programs in clinical stages worldwide.
Dr. Yuxuan Wu, founder of YolTech Therapeutics, stated: "The RMAT designation for YOLT-202 represents another important regulatory milestone for YolTech in the in vivo gene editing field, and reflects the continued progress of our in vivo gene editing platform. We will continue to advance the clinical development of YOLT-202, committed to bringing a potential 'one-and-done,' durable treatment option to AATD patients, and to continuously exploring differentiated therapeutic strategies for serious genetic diseases."
