CAMBRIDGE, Mass.—Moderna Inc. is looking for new fields to sow in the therapeutic world as it enters the realm of autoimmune and inflammatory diseases. But the clinical-stage biotech company—which says it is “pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients”—is doing so with a solid base, building on work it has already done and riding the wave of clinical validation of systemic delivery of mRNA that was provided by data from its antibody against the chikungunya virus (mRNA-1944) program.
Along with that news, the company also announced that it will expand its pipeline of innovative vaccines in the near term, following six positive Phase 1 clinical trial readouts from its infectious disease portfolio and the initiation of a Phase 2 study for its cytomegalovirus (CMV) vaccine, designated mRNA-1647.
While Moderna’s pipeline is organized into six modalities, they are all based on similar mRNA technologies, delivery technologies and manufacturing processes, and the announcements derive from the fact that the company is confident that recent positive Phase 1 data from its infectious disease vaccine portfolio, including its complex CMV vaccine, and its chikungunya antibody program have de-risked its prophylactic vaccines and systemic therapeutics modalities.
Essentially, the company’s strategy is to leverage early programs within a modality to generate clinical data and insights that reduce the technology risk of subsequent programs and can accelerate the pace of expansion into new modalities.
“2019 was an inflection point for Moderna, with significant clinical advances resulting from our investments in science and manufacturing capabilities. The positive Phase 1 results from our CMV vaccine and chikungunya antibody programs validate our approach and help clinically de-risk the delivery technologies for our prophylactic vaccines and systemic therapeutics modalities. Based on these learnings, we are excited to enter a new therapeutic area in autoimmune disease and announce two new development candidates,” said Stéphane Bancel, Moderna’s CEO. “We are entering 2020 with clear priorities, a strong cash balance and a talented team of employees focused on achieving our mission. With our CMV vaccine, we are preparing for our first pivotal Phase 3 study, and we look forward to announcing additional new development candidates in our two clinically de-risked modalities, prophylactic vaccines and systemic therapeutics.”
Moderna currently has 21 mRNA development candidates in its portfolio and 13 of those are now in clinical studies.
As Moderna puts it, autoimmune diseases are characterized by immune activation in response to antigens normally present in the body, reflecting a loss of tolerance. Within this therapeutic area, the company is developing two potential medicines, mRNA-6231 and mRNA-6981, designed to engage peripheral tolerance pathways to dampen autoimmune activation and help restore immune homeostasis, thereby reducing autoimmune pathology.
For its part, mRNA-6231 is an mRNA encoding for a long-acting IL-2 mutein designed to preferentially activate and expand the regulatory T cell population, dampening the immune response, while mRNA-6981 is an mRNA encoding for PD-L1 and is designed to augment cell surface levels of PD-L1 on myeloid cells, providing co-inhibitory signals to self-reactive lymphocytes.
As an initial step to addressing a range of autoimmune indications, the company plans to conduct a Phase 1 study of mRNA-6231 in healthy adult volunteers and intends to pursue proof-of-concept with mRNA-6981 in a Phase 1 study in type 1 autoimmune hepatitis, a condition that involves liver inflammation and can lead to cirrhosis and liver failure. The Phase 1 study of mRNA-6231 will be the first clinical demonstration of subcutaneous administration of this delivery technology.
Both of these new autoimmune development candidates share the same delivery technology as mRNA-1944, the antibody against chikungunya. The autoimmune therapeutic area is Moderna’s fifth therapeutic area, joining the areas of infectious disease, immuno-oncology, rare disease and cardiovascular disease.
Moderna also provided a financial update around the same time, noting that it is experiencing continued growth across the organization, having ended 2019 with approximately 820 full-time employees, compared to 735 employees the year before. In addition, reiterating prior guidance, the company expects 2020 net cash used in operating activities and purchases of property and equipment to be between $490 million and $510 million. Moderna currently has strategic alliances for development programs with AstraZeneca and Merck Inc.; the Defense Advanced Research Projects Agency, an agency of the U.S. Department of Defense; and the Biomedical Advanced Research and Development Authority, a division of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services.