LYS-GM101

As of the end of September, Lysogene reported having enough cash to last until the end of January 2023. With cash running out and a number of strategic options under consideration to stay afloat, Lysogene was banking on a clinical home run from its lead asset to woo investors. But new data presented by the company are anything but a splash.  The company’s top pipeline candidate, LYS-SAF302, failed its phase 2/3 trial among patients with mucopolysaccharidosis type IIIA (also known as Sanfilippo syndrome), a neurodegenerative disease that can spur a wide range of bodily dysfunction, including infections, dementia, sleep disturbances and propensity to chew on objects. Much of the symptoms begin to appear in early childhood. The company reported Friday that among the six youngest participants in the trial— kids younger than 30 months—there was a statistically significant improvement in cognitive function compared to natural history two years after dosing. Among the remaining 12 participants—"the main cohort"—a treatment effect wasn’t found. Development was measured using one of two different scales that assess neurodevelopmental and cognitive delay.  The results come almost a year after Sarepta decided to walk away from a deal to hold ex-Europe rights to LYS-SAF302, a collaboration that cost $15 million in upfront cash in addition to $125 million in biobucks. At the time, Lysogene said the termination had to do in part with “unsuccessful discussions” regarding the transferring of commercial supply of the therapy back to Lysogene.  But the fact of the matter is that Lysogene is facing a significant cash crunch given its clinical ambitions. As of the end of September, the company had roughly $6.3 million on hand, enough to last until the end of January. Lysogene is bullish that the data presented today, particularly the encouraging results in children under 30 months, will be enough to fundraise on. The company said in its announcement that strategic discussions are “progressing” with a priority placed on landing a new licensing deal.  The only additional clinical asset in Lysogene's pipeline is LYS-GM101, a treatment for the genetic neurological disorder GM1 gangliosidosis. The condition progressively destroys nerve cells in the brain and spinal cord. In late September, the company said (PDF) that it had enrolled five patients for the initial phase 1 trial focused on safety. If all goes well, Lysogene expects to begin enrollment for an additional 12 patients in early 2023. 

Lysogene and Sarepta Therapeutics will end a licensing agreement after failed discussions of transferring global commercial supply rights for the LYS-SAF302 asset back to Lysogene. Paris-based Lysogene announced Thursday morning that its license agreement with Sarepta Therapeutics for LYS-SAF302, a late-stage gene therapy for MPS type IIIA, will end on July 11, 2022. Lysogene, a gene therapy company focused on treating orphan diseases of the central nervous system, signed a deal in October 2018, granting Sarepta the rights for its experimental treatment LYS-SAF302 outside Europe. The deal could have brought in $125 million in milestones to the French firm. However, it was ended after a failed discussion about transferring global commercial supply rights for the LYS-SAF302 asset back to Lysogene. With the termination of the agreement, Lysogene will gain back commercial and development rights for LYS-SAF302 in the U.S. and non-European Union territories. As Lysogene pushes through with clinical trials, the company will receive compensation for reimbursing certain costs associated with the termination. Karen Aiach, founder, chairman, and CEO of Lysogene, believes that the LYS-SAF302 program is an important treatment option for patients suffering from MPS type IIIA, a rare genetic condition that causes fatal brain damage (also known as Sanfilippo syndrome, a rare and incurable neurodegenerative disease). Aiach thanked Serepta for its contribution to the LYS-SAF302 program over the past years. Aiach assures that Lysogene remains fully committed to the MPS type IIIA community and is dedicated to developing a treatment for MPS IIIA. The company will keep focusing its resources on its strategic objective of becoming the leading gene therapy technology platform targeting diseases of the central nervous system (CNS). “Our priority remains to execute on our existing pipeline with the completion of the LYS-SAF302 pivotal trial, the respective completion and initiation of the recruitment of the safety and efficacy cohorts of the LYS-GM101 clinical trial for the treatment of GM1 gangliosidosis and move forward our pre-clinical programs in Fragile X and nGaucher/Parkinson. We are also constantly looking for opportunities to further expand our pipeline with new CNS gene therapy assets,” Aiach said. It is hypothesized that LYS-SAF302 can slow and even reverse the neuro-developmental damage suffered by children with mucopolysaccharidosis type IIIA (MPSIIIA) or Sanfilippo syndrome type A. Lysogene received Orphan Drug Designation in the U.S. and European Union and Rare Pediatric Disease Designation from the U.S. Food and Drug Administration (FDA) for LYS-SAF302. LYS-SAF302’s efficacy, safety, and tolerability are currently being evaluated in an international phase II/III trial, the AAVance (NCT03612869) study , involving 20 children with MPS type IIIA. Data analysis for the primary endpoint of this registration study is scheduled for mid-2022, as initially anticipated. Lysogene shares dropped by 1.8% to 1.866 euros on the stock market this morning, lowering its capitalization to 32.2 million euros (against around 82.1 million when it was listed in February 2017).