Moderna’s mRNA Pipeline Shows No Sign of Slowing Down on R&D Day

Adam Glanzman/Getty Images

Adam Glanzman/Getty Images

This week, the mRNA leader followed up its announcement of a collaboration with the Institute for Life Changing Medicines (ILCM), with an update on several programs advancing in its pipeline.

Adam Glanzman/Getty Images.

With the world’s second most popular COVID-19 vaccine under its belt, Moderna is clearly not content to rest on its laurels. This week, the mRNA leader followed up its announcement of a collaboration with the Institute for Life Changing Medicines (ILCM), with an update on several programs advancing in its pipeline.

First, let’s take a look at the collaboration, which essentially amounts to a donation on the part of Moderna – because when you make a lot of money and keep it all, you begin to look impolite. On Tuesday, the company announced that it would license an asset, mRNA-3351, to ILCM with no upfront fees and no downstream payments to be developed by the latter for the treatment of Crigler-Najjar Syndrome Type 1 (CN-1).

CN-1 is an ultra-rare genetically inherited disorder caused by a mutation in the UGT1A1 gene in which bilirubin cannot be broken down. Lacking this critical enzyme, bilirubin builds up in the body, causing damage to the brain, muscles and nerves.

It affects approximately 1 in 750,000-1,000,000 people worldwide, patients who must endure up to 14-16 hours of phototherapy treatment a day for life. The only definitive treatment is a liver transplant, which comes with its own serious risks.

Moderna Chief Executive Officer Stéphane Bancel evoked the obstacles found by extremely rare diseases in the pharmaceutical industry.

“At Moderna, 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,” he said. “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.”

Moderna followed this up on Thursday with an update from its fifth annual R&D Day. Piquing possibly the most interest was the announcement of a single dose vaccine that combines a booster against COVID-19 and a booster against the flu – something of particular interest given the approaching Fall season.

“Our number one priority as a company right now is to bring to market a pan-respiratory annual booster vaccine, which we plan to always customize and upgrade,” Bancel stated during the R&D focus day.

Other significant news included positive new interim Phase I data from the company’s respiratory syncytial virus (RSV) vaccine candidate in older adults. Moderna stated that the vaccine elicited neutralizing antibodies in all participants at all dose levels with mRNA-1345 and boosted antibodies by approximately 14-fold against RSV-A and 10-fold against RSV-B. A single vaccination at each dose proved to be well-tolerated at the one-month mark. A phase II/III study is expected to begin by the end of 2021.

The company also revealed a new pediatric combination vaccine candidate (mRNA-1365) merging mRNA-1345 with its investigative hMPV vaccine. There is currently no approved vaccine to prevent RSV, which is the leading cause of severe respiratory illness in young children and older adults 65 and above, and Moderna is in competition with Pfizer, among others, to achieve the first. Pfizer’s RSV vaccine candidate recently entered Phase III.

Moderna also announced the full enrollment of several vaccine trials, highlighting a phase II study of its personalized cancer vaccine, mRNA-4157, which it is testing in combination with Merck’s Keytruda® compared to Keytruda alone, for the adjuvant treatment of high-risk resected melanoma. The primary endpoint for the study is recurrence-free survival at 12 months.

Of course, Moderna also gave updates on its COVID-19 vaccine, including variations in the works to address variants of concern Beta and Delta, and its Phase II/III trial of the vaccine in adolescents 12 to 17. Moderna has filed for emergency use approval in this age group in the U.S.

Moderna’s portfolio is comprehensive and diversified, with 37 programs in development, including 22 currently in clinical trials.

Last month, the company announced the launch of a Phase I clinical trial for its mRNA-based vaccine against HIV. The study will assess the safety and immunogenicity of the candidate in HIV-negative adult subjects 18 to 50. Moderna expects the trial to run until the spring of 2023.

On the therapeutic side, mRNA-3351 does not stand alone in Moderna’s rare disease pipeline. On August 23, the company announced that the first patient had been dosed in its phase I/II study of mRNA-3705, an investigational mRNA therapeutic for methylmalonic acidemia (MMA), another inherited disease in which the body cannot break down certain proteins and fats, leading to metabolic crisis.

“This is another step forward in Moderna’s mission to deliver on the promise of mRNA science to create a new generation of transformative medicines for patients,” said Dr. Ruchira Glaser, SVP and Therapeutic Area Head, Rare Disease, Autoimmune & Cardiovascular, who joined the company in January 2021.

This therapy is part of Moderna’s larger portfolio of systemic intracellular therapeutics which also includes a candidate for the treatment of Propionic acidemia, another rare autosomal recessive metabolic disorder, and a therapy for Phenylketonuria (PKU), a rare disorder caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine.

Now that mRNA has proven its worth in the vaccine setting (by saving the world from COVID-19), hopes are understandably raised for its potential in other areas. These include replacing missing or defective proteins in genetic diseases such as CN-1 and PKU, making antibodies, and potentially even gene editing.

Already established in the areas of infectious disease and oncology vaccines, decisions like bringing on Glaser – who was previously head of clinical sciences for the respiratory and specialty areas, including rare diseases, immunology and anemia at GlaxoSmithKline – point to Moderna’s commitment to remain on the forefront of mRNA innovation.