Moderna Edges Closer To Becoming A Mid-Stage Drug Development Company
Executive Summary
The mRNA specialist outlined ambitious plans to bring a vaccine for cytomegalovirus to market during an R&D day after releasing positive Phase I data.
Moderna Inc. hopes to move a wholly owned messenger RNA (mRNA) vaccine for cytomegalovirus (CMV) into Phase III development quickly after releasing positive interim Phase I results. The company announced the clinical data on 12 September and held an R&D day in New York City highlighting the development strategy for the vaccine, mRNA-1647, and other pipeline ambitions.
The product will be one of the company's first to move into mid-stage development, so it is getting a lot of attention. With limited clinical data until now, Moderna has been best known for its financing prowess. Last year, the company went public through a $604m IPO, the largest ever for a US biopharma, and that followed an impressive VC financing run. (Also see "Top Financings: 2018 Was A Remarkable Year For Biopharma Fundraising" - Scrip, 9 Jan, 2019.)
The company had a remarkable $1.44bn in cash as of June 30, although its stock value has dropped significantly since it went public at $22 per share. The stock opened 12 September at $16.23.
Management outlined an aggressive development path for the CMV vaccine, including a rapid Phase II test to confirm dosing and manufacturing supply, followed by a large Phase III trial that the company said it has already discussed with the US Food and Drug Administration.
The goal is ambitious, however, given the challenges associated with developing novel vaccines, particularly considering the vaccine would be given to women of child-bearing age to prevent newborns from contracting the virus. It's a proposition that will involve unique development and commercial challenges.
"The immediate step for us is to go and confirm the dose and confirm the pivotal manufacturing process in our Phase II," Chief Medical Officer Tal Zaks told investors. The Phase II protocol already has been submitted to the FDA for review and should start shortly, he added, with a rapid readout expected based on immunogenicity after three months and again after a second dose.
As for a Phase III trial, that study would enroll thousands of patients – somewhere around 8,000 women, Zaks predicted – to measure prevention of CMV infection. FDA has guided that endpoint would be sufficient for approval versus demonstrating protection in newborns.
"That is really a game-changer for us," Zaks said, remarking that the Phase III trial is feasible for a company the size of Moderna.
A Blockbuster-Sized Opportunity
CMV is a common pathogen in the herpesvirus family that is the leading infectious cause of birth defects in the US, including neurodevelopmental disabilities, hearing loss and vision impairment. It is common in healthy babies and toddlers who can pass it onto pregnant mothers, who then transmit the virus to their unborn child. Approximately 25,000 newborns are infected every year.
Moderna sees a large commercial opportunity if its product is the first vaccine for CMV to reach the market, with management referencing the success of vaccines like
Merck & Co. Inc..'s human papilloma virus vaccine Gardasil and Pfizer Inc.'s pneumococcal vaccine Prevnar, both blockbuster vaccines. The company expects a vaccine for CMV might be given to adolescent girls, depending on the durability of the product.
The total addressable market could be as high as 70m vaccinations a year, Moderna said, with a focused sales effort on obstetricians/gynecologists and pediatricians.
Moderna's vaccine combines six mRNAs in a single vial, encoding for two antigens on the surface of CMV: five encoding the subunits that form the membrane-bound pentamer complex and one mRNA encoding the full-length membrane-bound glycoprotein B (gB). Both are essential for CMV to infect barrier epithelial surfaces and gain access to the body, according to the company.
The vaccine produced an immune response that reached or exceeded levels generated by natural CMV infection, and was safe and well tolerated, the company reported. The ongoing Phase I study is evaluating the safety and immunogenicity of mRNA-1647 in 169 healthy volunteers, including people who are naïve to CMV infection (CMV-seronegative) and those who had previously been infected by CMV (CMV-seropositive).
Participants were randomized to receive either placebo or 30, 90, 180 or 300ug of mRNA-1649 at 0, two and six months. The interim analysis at three months assessed the safety and immunogenicity of the first three dosing levels at three months, one month after the second vaccination and before the third vaccination.
Moderna is up against one big pharma, Merck, to bring a CMV vaccine to market. Merck's product, V160, is being tested for safety and immunogenicity in a Phase IIb trial in healthy seronegative women 16 to 35.
Moderna highlighted other pipeline developments as well, including clinical data from an antibody against Chikungunya virus (mRNA-1944), also from an initial Phase I trial. MRNA-1944 is being developed with support from the US Department of Defense's Defense Advanced Research Projects Agency (DARPA) and is the first of the company's systemic therapeutics mRNA platform to show production of a secreted protein in humans.
"In three and a half years, the team has put 16 different molecules into the clinic," CEO Stéphane Bancel said. "That speaks loudly of the team, the platform and the investment."