Moderna touts early-stage data from mRNA therapies for cytomegalovirus, chikungunya virus

Moderna released interim results on Thursday from two Phase I studies of its experimental mRNA therapies for cytomegalovirus (CMV) and the chikungunya virus, with the former programme set to advance to mid-stage development. "I am very encouraged by the ability of mRNA-1647 to induce high levels of durable immune responses that can reach or exceed the levels generated by natural CMV infection," remarked chief medical officer Tal Zaks. The company's shares jumped as much as 12% on the news.

The first study is evaluating mRNA-1647, a vaccine combining six mRNAs that encode for two antigens on the surface of CMV, in 169 healthy adults, including those who were naïve to the virus and those who had previously been infected. Subjects were randomised to receive either placebo or 30 mcg, 90 mcg, 180 mcg or 300 mcg of mRNA-1647 on a dose schedule of zero, two and six months. Moderna noted that the first planned interim analysis included the first three doses of mRNA-1647 at three months

Results showed that in seronegative people, neutralising antibody titers in epithelial cells were three- to five-times higher than CMV-seropositive baseline titers at the 90 mcg and 180 mcg dose levels. Meanwhile, in fibroblasts, neutralising antibody titers were equivalent to CMV-seropositive baseline titers at the 90 mcg and 180 mcg dose levels. The company added that in subjects previously infected with CMV, a dose-related increase in neutralising antibody titers was also seen in both epithelial cell and fibroblasts, with increases from baseline of up to 19-fold and four-fold, respectively.

Moderna noted that in the second study, the administration of mRNA-1944 via intravenous infusion in healthy adults led to detectable levels of CHKV-24 antibody in all participants, ranging from 1 mcg/mL to 14 mcg/mL. Zaks said the "data represent a significant scientific breakthrough: this study shows for the first time the ability to generate therapeutic levels of a complex protein in humans through systemic administration of an mRNA, essentially instructing the body to make its own medicines."

However, Moderna indicated that one subject in the trial who received the higher dose of mRNA-1944 experienced Grade 3 adverse events of tachycardia and an elevated white blood cell count, while the patient also suffered from Grade 2 adverse events of nausea, emesis, fever and inverted T waves on a routine EKG. The company indicated that further work on mRNA-1944 is ongoing, which may include dosing in combination with commonly used steroid premedications to prevent infusion-related reactions.

The study has so far enrolled 22 healthy adults, with the initial analysis including subjects who received mRNA-1944 at three dose levels of 0.1 mg/kg, 0.3 mg/kg and 0.6 mg, or placebo. Moderna's therapy, which is being developed with financial support from the US Department of Defense's Defense Advanced Research Projects Agency (DARPA), encodes for the CHKV-24 antibody, which has activity against the chikungunya virus.

Moderna said that based on the results, it is advancing mRNA-1647 to a dose-confirmation Phase II study in the near term, while preparations have also begun for a pivotal Phase III trial designed to evaluate efficacy against primary CMV infection. CEO Stéphane Bancel commented "given the urgent need for CMV prevention around the world, we believe mRNA-1647 has the potential to be a blockbuster commercial opportunity." The executive indicated that mRNA-1647 will be tested in adolescents and infants.

In December last year, Moderna raised more than $600 million via its initial public offering after selling nearly 26.3 million shares at $23 a piece, giving the company a market value at the time of almost $7.9 billion.

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