Moderna Gives Updates on Its Diversified Pipeline at R&D Day

It was Moderna’s R&D day on 17th September. Starting with the COVID-19 front’s progress, the company discussed new developments in the oncology and rare diseases avenues. Here are some of the highlights from Moderna’s R&D day.

By Ruchi Jhonsa, Ph.D.

Update on Prophylactic Vaccination

Even before the COVID pandemic struck, Moderna had been developing mRNA vaccines against viral diseases where there is an unmet medical need. This list includes nine vaccines for common diseases as well as for diseases posing a global threat.

Moderna’s much-touted vaccine for novel coronavirus is currently leading the lot. It is already in the Phase 3 study and as of September 12, the study has enrolled 25,296 participants in the trial. The interim analysis of the Phase 1 trial of the mRNA-1273 vaccine resulted in rapid and strong immune responses against SARS-CoV-2 with no reported serious adverse events.

Moderna’s CMV vaccine is second in line, in terms of advancement in the trials. Moderna reported Phase 2 interim data for its CMV vaccine. The vaccine induced 12-fold higher neutralizing antibody titers in participants who were not previously exposed to the virus. But interestingly, a greater than 20-fold titer response was observed in patients who had been previously exposed to the virus. With exceptional efficacy data, a remarkable safety profile was observed for the vaccine with the most common adverse event being headache, fatigue, and myalgia. Moderna now plans to run the Phase 3 trial based on this data, expected to begin in 2021.

While these two vaccines have reached late-stage trials, Moderna’s other vaccine products are still in early clinical or preclinical stages. Moderna reported the progress of some of these vaccines. The company has initiated a Phase 1 study of human metapneumovirus and parainfluenza type 3 vaccine by dosing 10 infants (12-36 months of age). The trial recruitment was stopped due to pandemic, but the sites have re-opened and are actively recruiting. Vaccine for the pediatric respiratory syncytial virus (mRNA-1345) has undergone FDA review and has proceeded to the clinic. This vaccine is meant to give protection against RSV in young children. In the future, the company plans to combine mRNA-1345 with mRNA-1653 that will create a vaccine combo meant for protection against RSA, hMPV, and PIV3.

The company is now advancing in the seasonal flu business. The occurrence of a seasonal illness is not only debilitating to the patient but also places a burden on the healthcare system. Currently, approved vaccines are only 40-60% effective, which demands a higher efficacy vaccine.

Related Article: Vaccines Developing Can Catch Up SARS-CoV-2 Mutating?

Advances in Systemic secreted and cell surface therapeutics

The company is also using mRNA technology to supply secreted proteins such as antibodies or enzymes in the circulation to treat a wide range of diseases, such as heart failure, infectious diseases, and rare genetic diseases. Under this category, the company has started a Phase 1 trial of mRNA treatment for Chikungunya. The mRNA drug, mRNA-1944 is currently in the phase 1 trial where it is being administered in two cohorts, one with steroid pretreatment and the other without. According to the interim data, mRNA-1944 produced a dose-depended surge in neutralizing antibodies against the chikungunya virus at all dose levels. The drug was generally found safe and well-tolerated.

Moderna in cancer therapy

Moderna is also using its mRNA platform to develop mRNA therapies that drive anti-cancer T cell responses in the tumors. The company currently has three intratumoral immune-oncology programs. One of its programs uses mRNA to produce OX40 ligand in the tumors. OX40 is a co-stimulatory membrane-bound protein that promotes expansion, function, and survival of T cells. The company believes that by expressing OX40 ligand in the tumor, the drug might promote a stronger T cell attack against the tumor. Currently, the trials are ongoing to test the efficacy of checkpoint inhibitor, durvalumab combined with the company’s mRNA drug. The data from the Phase 1 study evaluating mRNA-2416 as a monotherapy showed a favorable safety profile for the drug. It remains to determine whether mRNA drug would augment durvalumab’s efficacy against advanced ovarian carcinoma.

RNA Therapeutics: An Overview

Treating disease at its home

Another interesting avenue in which Moderna is currently invested is of systemic intracellular therapeutics. This program aims to deliver mRNA into cells within the target organs for treating diseases caused by a missing or defective protein. The company is currently pursuing two disease targets, Methylmalonic academia (MMA) and Propionic academia (PA). Although the company had initiated trial enrollment for these indications, they had to be stopped to ensure the patients’ safety in the current pandemic situation. Meanwhile, the company has revised its protocols and implemented changes, including introducing a new drug product with better pharmacology in the MMA trial and the introduction of a novel design to identify the optimal dose in PA study.

As for the corporate updates, Moderna has entered in research collaboration with Vertex to discover potential treatment of cystic fibrosis using Moderna’s mRNA and lipid technologies. It has also collaborated with Chiesi Group to discover and develop mRNA therapeutics for pulmonary arterial hypertension.

Related Article: COVID-19 Vaccine: Moderna Gets $483M Funding Boost from BARDA

References:

1. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-progress-across-broad-portfolio-and-all-three

2. https://www.modernatx.com/pipeline/mrna-2416

Author

Ruchi Jhonsa