Rare Daily Staff

Zogenix is adding to its rare disease pipeline with the acquisition of Modis Therapeutics, a company focused on developing novel therapies for rare genetic diseases with high unmet medical need for $250 million in cash and stock and the potential for $150 in milestones.

Modis’ lead product candidate, MT1621, is an experimental therapy in late-stage trials as a treatment for thymidine kinase 2 deficiency, an inherited mitochondrial DNA depletion disorder that predominantly affects children and is often fatal.

Thymidine kinase 2 deficiency (TK2d) is a genetic disorder that results in mitochondrial dysfunction, leading to inadequate energy production in cells. TK2d causes progressive and severe muscle weakness, respiratory insufficiency, loss of motor function, and is often fatal. Symptom onset varies from infants to adults. There are currently no approved therapies for this disease. TK2d affects up to 2,500 patients in the United States, primarily infants and young children, and there are currently no approved therapies for this disease.

MT1621 is a therapy that targets the underlying pathophysiology of TK2d by restoring mitochondrial DNA replication fidelity. The drug candidate consists of a combination of deoxynucleosides (the building blocks of mtDNA) given orally as a dissolved solution that has been shown in preclinical models of TK2d to improve nucleotide balance, increase mtDNA copy number, improve cell function, and prolong life.

A recently completed pivotal retrospective treatment study of MT1621 showed positive benefit for TK2d patients. Thirty-eight patients from eight clinical sites in three countries received MT1621 treatment for up to seven years. Outcomes from patients enrolled in the study were compared to outcomes from a comprehensive, global TK2d natural history dataset of 68 patients. The difference in survival probability between MT1621-treated patients and untreated natural history control patients was statistically significant in that all treated patients treated remain alive. They also showed marked improvements in functional abilities, in some cases re-acquiring previously lost motor milestones. Safety data indicated that MT1621 was generally safe and well-tolerated, although two adult-onset patients had to drop out of the study due to problems that resolved with discontinuation of treatment.

“Based on the compelling clinical data generated to date, we believe that MT1621 has the potential to significantly alter the course of the disease and improve outcomes in patients with TK2d,” said Stephen Farr, president and CEO of Zogenix. “With Breakthrough Therapy and PRIME designations, MT1621 may be eligible for an accelerated regulatory path in both the U.S. and Europe, and we look forward to meeting and working with regulatory authorities to discuss next steps for the program.”

Under the terms of the deal, Modis will receive an upfront payment of $250 million, comprised of $175 million in cash and $75 million in Zogenix common stock. Modis is also eligible to receive additional milestone payments consisting of $100 million upon receipt of U.S. Food and Drug Administration approval of MT1621 in the United States and $50 million upon European Medicines Agency approval in Europe. Zogenix will also pay a 5 percent royalty on any future net sales of MT1621.

Modis Therapeutics was formed in 2016 through a collaboration with academic experts in mitochondrial biology at Columbia University Irving Medical Center and Vall d’Hebron Research Institute in Israel.

Photo: Stephen Farr, CEO of Zogenix

X