Moderna, ILCM to Develop mRNA Therapeutic for Ultra-Rare Disease

Moderna and the Institute for Life Changing Medicines (ILCM) recently collaborated to develop a new mRNA therapeutic (mRNA-3351) for ultra-rare disease, Crigler-Najjar Syndrome Type 1 (CN-1). 

CN-1 is an ultra-rare genetically inherited disorder caused by the mutation in the UGT1A1 gene in which bilirubin cannot be broken down. Bilirubin can then build up in the body, lead to jaundice, and damage the brain, muscles, and nerves. 

There are only about 70 to 100 known cases of CN-1 globally. But the symptoms of the disease become apparent shortly after birth and can be life-threatening.

The companies will aim to make mRNA-3551 available to patients at no cost as part of the collaboration. So ILCM will not pay Moderna an upfront fee or any downstream payments, while Moderna will provide the mRNA-3351 material free of charge. 

“We believe that mRNA therapies have the potential to profoundly impact rare disease patients and their families. Ultra-rare diseases are always a challenge for our industry given the very small number of patients who could benefit from the medicine,” Stéphane Bancel, chief executive officer of Moderna, said in the announcement.

“We decided that rather than charge a high price for the medicine candidate, which is not aligned with our values, we would rather give it away for free,” Bancel continued. 

mRNA-3351 is designed to restore the missing or dysfunctional proteins that cause CN-1.

Notably, the therapeutic uses the same proprietary LNP formulation as Moderna’s antibody against chikungunya virus, mRNA-1944, propionic acidemia, mRNA-3927, and methylmalonic acidemia, mRNA-3704, programs. 

FDA previously granted mRNA-3351 Rare Pediatric Disease designation.

The current standard of care treatments for CN-1 relies on phototherapy treatments of up to 12 hours a day throughout life. 

During phototherapy treatment, the patient’s bare skin is exposed to intense light while the eyes are shielded. The process helps to change the bilirubin molecules in the skin to be excreted in bile without conjugation. 

But body mass increases over time and the skin thickens, making phototherapy less effective for preventing brain damage. Therefore, the only definitive treatment for CN-1 is a liver transplant, which also comes with its own side effects and risk of death.

ILCM plans to initiate clinical studies of mRNA-3351 in 2022.

“We are energized to collaborate with Moderna to advance an mRNA for treating Crigler-Najjar,” said Alex Karnal, co-founder and chief executive officer of ILCM. 

“We are grateful for Moderna’s support of our novel nonprofit business model by providing our first medicine aimed at transforming the lives of people suffering from Crigler-Najjar syndrome around the world,” Karnal continued.