mRNA-1083

A messenger RNA strand iStock/ libre de droit The potential of mRNA vaccines was established during the COVID-19 pandemic. Now, a new wave of candidates could soon hit the market for cancer, influenza and more. The arrival of the COVID-19 pandemic heralded an unprecedented period for the pharmaceutical industry, with vaccines progressing from R&D to worldwide rollout in record time and garnering record-breaking profits for developers. The FDA approval of the mRNA vaccines themselves was also a landmark event, acting as a proof of concept and ushering in this new class of treatments. “COVID-19 accelerated the timelines of the mRNA pipeline, opening the aperture for the companies to start expanding more broadly into other infectious diseases and then to continue to advance the non-infectious disease part of their mRNA pipelines,” said Jennifer Heller, a partner at McKinsey & Company, which recently published a report on innovation in vaccine development. This is what happened for Moderna, which recently followed its COVID-19 vaccine with the FDA approval of a respiratory syncytial virus (RSV) vaccine. The global mRNA therapeutics market size is expected to reach $68 billion by 2030, according to Statista . Within the overall vaccine pipeline, Heller told BioSpace that mRNA technology is disproportionately represented when compared to other technologies, particularly in Phase I trials. One advantage for mRNA developers is that they can rapidly develop a potential product, as happened during the pandemic . This means that the growth in mRNA vaccines at the early stage of the pipeline could soon be seen later on. It could also establish the technology’s advantage over traditional vaccines, which typically take between five and 10 years to develop and bring to the market. “The advantage of being able to rapidly create a product that can be tested in the clinic lends itself to accelerated development and that’s been the promise of this technology platform,” Heller said. “I think we’re still in early days and so we’ve only had a few products to look at, but I think the trend suggests favorable timelines.” Here, BioSpace highlights five mRNA vaccine candidates that could reach patients in the near future. Pfizer/BioNTech’s PF-07252220 Influenza and an influenza/COVID-19 combo Since successfully developing COVID-19 vaccine Comirnaty, Pfizer and BioNTech have extended their collaboration to build a pipeline of mRNA vaccines. The next likely candidate for approval is an influenza vaccine, PF-07252220, with Pfizer last year releasing Phase III trial results that demonstrated “superiority to a licensed flu vaccine” in participants 18 to 64 years of age. The partners also plan to move forward with a combination mRNA vaccine against both influenza and COVID-19. However, this move was struck a recent blow when the companies announced that the vaccine met only one of its two primary immunogenicity endpoints. While specific data were not provided, they reported that the combination vaccine had strong efficacy against influenza A but was weaker against the influenza B strain. The companies said they will consider “adjustments” to the candidate, but this is likely to result in delays before any potential approval and the possibility of losing ground to rivals. Moderna’s mRNA-1083 Influenza/COVID-19 combo With Pfizer hitting a stumbling block, Moderna’s COVID-19/influenza vaccine, mRNA-1083, could be the first such combination vaccine to reach the market. In June, the company posted results from a Phase III trial that showed mRNA-1083 produced a strong immune response against both COVID-19 and influenza. In releasing the results, Moderna also became the first and, due to Pfizer/BioNTech’s struggles, only company to date to post positive Phase III results for a combination COVID-19/influenza vaccine. The efforts by both Pfizer/BioNTech and Moderna can be seen as a strategy to extend the sales enjoyed by the standalone COVID-19 vaccines. One of the obvious marketing benefits would be the ability to provide the vaccine annually, each flu season. An additional selling point could be improved efficacy over existing vaccines, with Moderna stating that its combination vaccine candidate was more effective at providing immunity in adults over the age of 50 than competing influenza and COVID-19 shots. Moving forward, Moderna plans to add its newly approved RSV vaccine to the combination, creating a triple shot against all three infectious diseases. GSK/CureVac’s GSK4382276 and GSK4388067 Influenza and, separately, COVID-19 GSK is also targeting both influenza and COVID-19, though currently with separate products. In July, the British multinational bought the global rights to develop CureVac’s investigational mRNA vaccines against COVID-19 (GSK4388067) and influenza (GSK4382276), with the option to develop a combination and an additional vaccine against avian flu. GSK4388067 and GSK4382276 are both currently in Phase II trials and are therefore not too far behind their rivals. On securing full rights to the vaccines, GSK Chief Scientific Officer Tony Wood said in a statement that the company would apply its capabilities “to deliver these promising vaccines at pace.” Moderna’s mRNA-4157 Head and neck cancer and melanoma Oncology is one of biopharma’s key markets, and if mRNA vaccines can prove effective in the space, it could be a validation of the technology’s broader therapeutic and commercial potential. Moderna is developing mRNA-4157, a therapeutic vaccine currently being explored in Phase III. The vaccine is being developed in partnership with Merck and paired with Merck’s Keytruda in hopes that it will be able to boost the efficacy of the PD-1 inhibitor to provide a greater anti-tumor effect. The product is currently being trialed in various oncology indications, including head and neck cancer and melanoma. Heller said that though McKinsey is seeing significant investment go into the therapeutic vaccine space, particularly for those targeting oncology, the “business case needs to be proven.” She added that should mRNA vaccines prove to be effective in the space McKinsey expects a number of follow-on assets to emerge, which could target other indications such as rare diseases. For the moment, the main focus of the vaccine pipeline remains infectious disease and respiratory conditions, Heller said. Moderna’s mRNA-1647 Cytomegalovirus Finally, Moderna is developing mRNA-1647 for cytomegalovirus (CMV), the most common infectious cause of birth defects in the U.S. The vaccine is currently being evaluated in Phase III for primary CMV infection in women 16 to 40 years of age. The first interim analysis of the vaccine’s efficacy is expected by the end of 2024, Moderna stated in March. The company has also advanced indication expansion studies in adolescents 9 to 15 years old and in adult transplant patients. In Phase II results , antigen-specific immune responses were observed at all dose levels in both CMV-seronegative and -seropositive participants, with the vaccine also being found to be generally safe and well-tolerated. There are currently no approved vaccines to prevent congenital CMV and no treatments for CMV in pregnancy. The virus is typically harmless to adults but can cause a range of health problems in babies and people with a weakened immune system.

This illustration is a JPG File to depict Entrepreneurship skills iStock, jauhari1 During an investor day Thursday, Moderna’s R&D chief Stephen Hoge detailed plans for the famed biotech to trim R&D spending in preparation for the launch of up to 10 new products. Moderna’s shares tumbled Thursday as executives revealed a plan to slow down the R&D engine that has cranked out respiratory products since the company rose to fame and profitability during the COVID-19 pandemic. The biotech said that the changes will allow it to fund all existing plans without raising equity, breaking even on an operating cash basis in 2028—pushed back from 2026—with $6 billion in revenue. But analysts were skeptical that additional funding wouldn’t be required. Jefferies had expected cash to be in excess of $6 billion to as high as $7 billion in the 2025 timeframe. “The company believes they have sufficient cash to fund their plans to break even without raising additional equity, however, we believe this will remain a significant debate, and investors are unlikely to believe this until further credibility,” the firm wrote in a note to clients. The investor day presentation followed Moderna’s announcement this week that it would cut annual R&D spend by $1.1 billion to reduce expenses by 2027, during which timeframe the biotech is also aiming to achieve 10 product approvals. But the information shared did little to reassure the company’s investor base, as shares slid 12% on Thursday to $69.68 at close, compared to $79.51 the day before. William Blair analysts said in a note to clients that investors were responding to the shift in the company’s breakeven guidance from 2026 to 2028. Another factor was the news that Moderna’s melanoma vaccine mRNA-4157, developed in partnership with Merck , was unlikely to receive accelerated approval as an adjuvant treatment for recurrent disease. Moderna Navigates Post-COVID Era Moderna, which is headed by CEO Stéphane Bancel, reinvested the $20 billion windfall it got from the COVID-19 pandemic back into its pipeline. Now, the company is faced with the fruits of that labor—and the challenges of launching multiple medicines at once, President Stephen Hoge, who leads all R&D for the company, said during the investor presentation. “It is a really daunting task, three launches a year on average for three years in a row, and we recognize that we have to show we can make progress on those launches before starting the pipeline and the engines again,” Hoge said. This year, Moderna has achieved approvals for its updated COVID-19 shot and its respiratory syncytial virus (RSV) vaccine mResvia. Those approvals are all in Moderna’s respiratory vaccine portfolio , which was able to tap into learnings from developing the COVID-19 vaccine called SpikeVax, Hoge said. Studies for those infections can also be conducted quickly because they are seasonal, he explained. Moderna plans three additional product submissions this year, using a priority review for one to speed up the process. The company will seek first approvals for next generation COVID-19 shot mRNA-1283 and a flu-COVID combo called mRNA-1083, which yielded positive Phase III data in June. It will also request a label expansion for mResvia to expand the eligible population. Moderna has also been working to diversify the pipeline that will define the biotech’s next era. Key programs going forward will be from the latent vaccines portfolio, such as the Phase III assets mRNA-1403 for norovirus and mRNA-1647 for cytomegalovirus. The goal has been for Moderna to start seeing substantial non-respiratory approvals in the 2026 timeframe, Hoge said this week. Those programs come from Moderna’s latent vaccines, rare disease and oncology portfolios. “It is an incredible body of work. And I hope you can see why we’re proud of the launches, but also why we’re daunted by the commercial challenge of launching all those products really just in the next three years,” Hoge said. “And that causes us to want to actually start to pace ourselves.” Moderna’s Pipeline Cuts Among the changes announced this week, Moderna plans to be more judicious about what rare disease and latent vaccine assets advance into pivotal development “until we’ve shown we can get these out the door,” Hoge said. The company will also slow down the respiratory spending that became the focus of the initial COVID-19 funds, with no new pivotal trials expected to begin for these products in the 2024–2025 timeframe, Hoge said. “As that naturally sunsets, there will be a reduction in our respiratory R&D investment. We’ve succeeded in that strategy,” he said. Moderna also trimmed around the edges of its pipeline. In respiratory, a preclinical endemic human coronavirus vaccine program called mRNA-1287 was removed and an infant RSV program called mRNA-1345 will not advance past an existing Phase I trial. In oncology, Moderna has no further development plans for a KRAS antigen-specific therapy called mRNA-5671, and the triplet XXXX therapy mRNA2752 is being shuttered. Finally, the cardiovascular relaxin program mRNA-0184 will wrap up after Phase I. For this year and next, Moderna’s average annual R&D spend is expected to be $4.6 billion. That number will drop to $3.8 billion for 2026 through 2028. Overall, that means spending will go from an expectation of $20 billion from 2025 through 2028 to $16 billion. The R&D reductions will begin next year and “hit its full scope” by 2027, Hoge said. The commercial respiratory franchise is expected to be profitable this year, with an expected $3 billion to $3.5 billion sales, but that revenue will not allow the company to break even until 2028. Both William Blair and Jefferies expected to see the profitability forecast pushed out, so the news was not much of a surprise to them. But both said the update left investors unconvinced. “With the stock trading down 18% intraday and a full 45% since the 2024 full-year product revenue guidance revision on the second-quarter earnings call, we believe Moderna is quickly becoming a show-me story to make this an investable story for new money again,” the William Blair analysts wrote.