Moderna (MRNA) excited analysts, though not as much investors, with its announcement this week that it planned to file for approval of its mRNA vaccine designed to protect older adults against respiratory syncytial virus (RSV) after it demonstrated success in a Phase III trial.
After the close of trading on Tuesday, Moderna reported positive topline data from its ConquerRSV Phase III pivotal efficacy trial (NCT05127434) of mRNA-1345 showing the vaccine candidate to have met the study’s primary efficacy endpoints, including vaccine efficacy (VE) of 83.7% (p<0.0001) against RSV-associated lower respiratory tract disease (RSV-LRTD), defined by two or more symptoms.
Based on the data, Moderna said it will file for FDA approval of mRNA-1345 during the first half of this year. If approved, mRNA-1345 would be Moderna’s second vaccine from its mRNA platform to gain authorization after the company’s blockbuster COVID-19 vaccine Spikevax™.
The submission plans, and the data underlying them, persuaded three analysts this week to raise their 12-month price targets on Moderna shares.
Michael J. Yee, equity analyst at Jefferies, and colleagues boosted the firm’s Moderna price target 44%, to $275 a share. He observed in a research note Wednesday that Moderna’s VE just edged the 82.6% reported by GlaxoSmithKline (GSK) in October 2022 for its RSV vaccine candidate, against RSV lower respiratory tract disease, meeting the primary endpoint of the Phase III AReSVi-006 in adult RSV (NCT04886596).
Moderna’s reported VE clearly surpassed the 66.8% reported in November by Pfizer (PFE) for its bivalent RSV prefusion vaccine candidate RSVpreF (PF-06928316), based on data from the Phase III MATISSE trial (MATernal Immunization Study for Safety and Efficacy; NCT04424316). Last month, the FDA accepted for Priority Review Pfizer’s Biologics License Application (BLA) for RSVpreF to prevent lower respiratory tract disease caused by RSV in individuals 60 years of age and older. The agency has set a Prescription Drug User Fee Act (PDUFA) target decision date for RSVpreF of May 2023.
“This further validates the strength of the mRNA platform and allows another potential revenue stream and further opens the door for the potential for combo vaccines which no other platforms can do,” Yee and colleagues wrote.
Two examples of potential combo vaccines in Moderna’s pipeline are mRNA-1230, designed to protect against COVID-19 and influenza as well as RSV; and mRNA-1045, focused on RSV and influenza. Both vaccine candidates are being assessed in a Phase I/II trial launched last year (NCT05585632).
Development scramble
Pfizer and GSK are among companies scrambling to develop RSV vaccines as the disease has seen increases in detections and associated emergency department visits and hospitalizations in several U.S. regions, some nearing seasonal peak levels, according to the U.S. Centers for Disease Control and Prevention (CDC).
Other companies pursuing development of RSV vaccines for older adults in recent years include Bavarian Nordic (BAVA) and Johnson & Johnson (JNJ). Bavarian Nordic said last month it had completed its planned enrollment of subjects in a global Phase III trial of its MVA-BN® RSV in adults ≥60 years of age, with more than 20,000 subjects enrolled at 120 sites across the United States and Germany. In December 2021, J&J’s Janssen Pharmaceutical Cos. announced vaccine efficacy of 70% to 80% in adults aged 65 and older in data from its Phase IIb CYPRESS trial (NCT03982199).
As for RSV in infants, AstraZeneca (AZN) and Sanofi (SAN) won European Commission approval in November for their vaccine Beyfortus (nirsevimab) to prevent RSV lower respiratory tract disease in newborns and infants during their first RSV season. According to the companies, Beyfortus is the first and only single-dose RSV passive immunization for the broad infant population, including those born healthy, at term or preterm, or with specific health conditions.
Geulah Livshits, PhD, a senior research analyst at Chardan covering biotech companies, raised the firm’s price target on Moderna 9%, from $191 to $208 a share. Also raising his firm’s Moderna price target 9% was Mani Foroohar, MD, senior managing director, genetic medicines, and a senior research analyst with SVB Securities—from $102 to $111 a share.
“Based on high-level comparison with VE from RSV vaccines from competitors PFE, GSK, and JNJ, we see these results as likely approvable and plausibly competitive with those agents,” Foroohar wrote, before cautioning: “This limited, topline disclosure offers an incomplete picture for comparison, and any numerical differences should consequently be taken with a grain of salt.”
Reducing market size estimate
Foroohar’s SVB colleague David Risinger, head of diversified biopharmaceutical research and a senior managing director, in October dialed back his estimate on the total size of the potential market for RSV vaccines for older adults, from the $7 billion he projected in August 2022 to $6 billion.
Risinger cited the assumption that prices for RSV vaccines would be lower than first forecasted as multiple jabs enter the market—the same reason why he also reduced his estimate of the size of market for RSV vaccines for infants from $3.1 billion to $2.7 billion.
The potential for a second revenue stream couldn’t come at a better time for Moderna. During the recent J.P. Morgan Healthcare Conference, Moderna CEO Stéphane Bancel presented unaudited results showing that Spikevax finished last year with approximately $18.4 billion in revenue—a 4% increase from the $17.675 billion the COVID-19 vaccine generated in 2021, and within the $18 billion to $19 billion range forecasted by the company in November when it released third-quarter 2022 results.
However, Moderna’s 2022 revenue for Spikevax fell 16% below the company’s initial guidance to investors last year, which projected that the vaccine would rack up $22 billion. For 2023, Moderna is forecasting that sales of Spikevax will start at a “floor” or at least $5 billion, reflecting confirmed advance purchase agreements and 2022 contract deferrals—namely between $2 billion and $3 billion worth of contracted sales of the COVID-19 vaccine.
The enthusiasm shown by analysts was not matched by investors. Moderna’s shares only rose 7% on the news, climbing from $190.69 to $203.21 in after-hours trading Tuesday, before settling for a 3% gain, closing at $197.02 on Wednesday. Moderna shares slid 3% to $190.38 on Thursday.
Leaders and Laggards
- Aceragen (ACGN) shares tumbled 33% from $8.64 to $5.76 on Thursday, the company’s second trading day since changing its name from Idera Pharmaceuticals and its symbol from IDRA, through a 1-for-17 reverse stock split that enabled the company to regain compliance with Nasdaq listing standards. This year, Aceragen said it expects to read out Phase II data for ACG-701, a treatment for acute pulmonary exacerbations in cystic fibrosis; and launch a Phase II/III trial in Farber disease for ACG-801 upon lifting of a clinical hold.
- Calyxt (CLXT) shares zoomed 90% on Tuesday, from $0.186 to $0.353, after the company announced plans to merge with Cibus to form a combined company intended to lead in agricultural-focused gene editing—specifically in the production of renewable low-carbon ingredients and the development of a new class of productivity traits via Cibus’ Rapid Trait Development System™ (RTDS®) platform. Cibus is launching three such traits: one in canola and two in rice with transfers to customers for commercialization beginning in the first half of 2023. The companies will merge via an all-stock transaction whose value was not disclosed.
- Celyad Oncology (CYAD) shares nearly tripled, rocketing 197% between January 13 and Wednesday, from $0.799 to $2.37, following a trading surge where 65.34 million shares changed hands Tuesday and 20.1 million shares the following day. The stock has more than tripled (up 228%) since December 21, when Celyad halted development of its relapsed/refractory multiple myeloma candidate CYAD-211 after a strategic and financial review as part of its Celyad 2.0 strategy, which includes prioritizing discovery research to address limitations of chimeric antigen receptor (CAR) T-cell therapies by modulating multiple genes through the short hairpin RNA platform, developing a next-generation NKG2D-based CAR, and develop B7-H6-targeting immunotherapies.
- NeuroSense Therapeutics (NRSN) shares soared 78% on Thursday, from $1.25 to $2.22 after it announced positive final results from a biomarker study of the company’s TDP-43 combination platform therapy for Alzheimer’s disease. Results showed elevated levels of TDP-43, the transactive response DNA binding protein of 43 kDa, in Alzheimer’s disease. NeuroSense said it planned to commence a Phase II double-blind proof-of-concept study in Alzheimer’s in the first half of 2023. TDP-43 is known to colocalize with senile plaques and neurofibrillary tangles, suggesting a direct interaction between TDP-43 and amyloid-β (Aβ) or tau, according to the company.