mRNA-1653

Pictured: Facade of Moderna’s building in Massachusetts iStock, hapabapa During Wednesday’s annual R&D Day, Moderna said it is culling four programs from its pipeline, including two molecules that had been discontinued last year by AstraZeneca. Pictured: Moderna headquarters in Massachusetts/iStock, hapabapa Moderna on Wednesday announced it was dropping four clinical development programs from its roster, including two molecules that had also been previously culled by AstraZeneca. The decision to discontinue the four clinical programs was part of Moderna’s routine review of its pipeline, in which it evaluates whether there are better opportunities and areas of focus for its mRNA-based drug discovery, design and development platform, President Stephen Hoge said during the company’s annual R&D Day. “We have a blessing and a curse in terms of how productive this platform is, and anytime we see an opportunity to focus our energy on programs that we think are the most important to move forward, we’ll do so,” Hoge said. Moderna’s pipeline cull will affect two formerly AstraZeneca-partnered molecules: the VEGF-A program AZD8601 and the IL-12 program MEDI1191. AZD8601 is an mRNA therapeutic encoding for VEGF-A. In November 2021, Moderna posted data from the AstraZeneca-led Phase II EPICCURE study, which found that injecting the candidate into heart tissue was safe and tolerable, while eliciting signals of efficacy such as improved left ventricular ejection fraction and patient-reported outcomes. AstraZeneca announced it was dropping AZD8601 from its roster in August 2022. A few months later, in November 2022, AstraZeneca also pulled its support from the IL-12 program MEDI1191, which it was studying as part of a combination regimen with the PD-L1 inhibitor durvalumab for the treatment of advanced solid tumors. MEDI1191 is a lipid nanoparticle-formulated candidate that induces the production of IL-12 and promotes anti-tumor activity. In addition to these two candidates, Moderna announced during Wednesday’s R&D Day that it was likewise dropping mRNA-1653, the company’s vaccine candidate for pediatric human metapneumovirus and parainfluenza type 3 virus. The investigational shot was being assessed in a Phase Ib study. Moderna is also abandoning its first-generation COVID-19 and flu combination vaccine mRNA-1073. During its 2022 R&D Day , the company announced that it was assessing the candidate in a Phase I/II trial. Moderna is also advancing a triple-target vaccine, mRNA-1230, which is likewise in a Phase I/II study for COVID-19, flu and respiratory syncytial virus. The news about culling four programs from its pipeline came the same day as the Massachusetts-based biopharma celebrated a Phase III victory for its mRNA-based flu vaccine candidate. Also revealed during Wednesday’s R&D Day, the investigational shot—dubbed mRNA-1010—met all its co-primary endpoints across all four influenza A and B strains, according to an interim analysis of the late-stage study. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

Moderna follows AstraZeneca's footsteps, dropping two programs the pharma already abandoned last year as well as two internal projects. Right after making headlines for a phase 3 mRNA flu shot win, Moderna shared that it’s axing four clinical assets from its pipeline—including two that AstraZeneca dumped last year. The Big Biotech cited pipeline prioritization being conducted “when needed” as the reason for the culls, according to a presentation (PDF) from Moderna’s R&D day. First up on the chopping block was AZD8601, a therapy based on mRNA encoding vascular endothelial growth factor (VEGF-A). Initially an AstraZeneca-partnered asset, the cardiovascular candidate became solely Moderna’s when the pharma dropped it from its pipeline last summer. Before removing it from its pipeline, AstraZeneca shared data from a phase 2a clinical trial where investigators injected the mRNA directly into the muscular heart tissue of patients undergoing elective coronary artery bypass surgery. Seven patients received AZD8601 while four received a placebo. AstraZeneca deemed the results positive, pointing to trends in the three exploratory endpoints, which looked at a biomarker that elevates in heart failure and functional patient-reported outcomes. The data offered early support for the use of AZD8601 to trigger production of VEGF-A, a paracrine factor involved in new blood vessel formation and the production of specialized cells that help repair the heart. However, despite those findings, AstraZeneca dropped the asset shortly after, with Moderna now following suit. The second program to receive the boot was MEDI1191, a program that originated from AstraZeneca’s own MedImmune and one the pharma also chose to leave behind. The IL-12 mRNA therapy was being studied in combination with immune checkpoint inhibitor Imfinzi in a phase 1 study for patients with solid tumors. Data shared in April 2022 revealed that three of the 31 patients who received the combination had partial responses. But AstraZeneca dumped the program in the fall, with Moderna now making the same move about a year later.  Next up was Moderna's mRNA-1653, a pediatric vaccine for preventing human metapneumovirus and parainfluenza virus 3 (hMPV/PIV3), which can cause respiratory tract illnesses in children and elderly adults. The wholly owned shot was assessed in a phase 1b study that enrolled 51 adults and children and wrapped at the end of 2022, though final data from the trial weren’t shared publicly.    Lastly, Moderna discontinued plans for its first-generation combination COVID-19 and flu vaccine dubbed mRNA-1073. The phase 1/2 program assessing the shot in 553 adults was completed at the end of 2022, though top-line data haven’t been publicly disclosed either.    The pipeline changes come just hours after the biotech announced a phase 3 win for an updated version of its mRNA flu vaccine, mRNA-1010. In February, the company modified the shot after its first version failed to meet the noninferiority threshold for the two influenza B strains. Now, the new version has met all the trial’s main goals, and Moderna’s CEO Stéphane Bancel is eyeing a launch as early as 2024.   Editor's note: Fierce Biotech has reached out to Moderna about the program discontinuations and will update this article as more information becomes available.