January 9, 2023 / Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced updates on its industry-leading mRNA pipeline. Moderna continues to scale, now with 48 programs in development, including 36 programs in clinical trials encompassing mRNA infectious disease vaccines and mRNA therapeutics spanning seven different modalities.
Respiratory syncytial virus (RSV) vaccine
•Pivotal Phase 3 RSV efficacy study (mRNA-1345) in older adults (60+) has enrolled 36,604 participants
•Primary endpoints are safety and vaccine efficacy
•The Phase 3 RSV study has now accrued the cases required (64 confirmed cases with 2+ symptoms accrued, minimum of 42 required) to complete our first interim efficacy analysis
Seasonal influenza vaccine
•mRNA-1010 Southern Hemisphere immunogenicity study in adults (18+) is fully enrolled (6,000 participants); data readout expected in 1Q23
•mRNA-1010 Northern Hemisphere efficacy study in older adults (50+) is fully enrolled (22,510 participants); data readout could occur this winter depending upon cases accrued in the study and vaccine efficacy
Vaccines against latent viruses
Cytomegalovirus (CMV) vaccine
•CMV is a common infection and is the leading cause of birth defects in the U.S. About 1 out of every 200 infants in the U.S. are born with congenital CMV infection (12,000-20,000 congenital CMV cases annually in the U.S. alone)
•Phase 3 CMVictory trial with mRNA-1647 is ~40% enrolled. Now enrolling in Japan
•CMV is a $2-5 billion opportunity with no approved vaccine on the market
Personalized cancer vaccine
•Moderna and Merck announced mRNA-4157/V940, in combination with KEYTRUDA, demonstrated a statistically significant and clinically meaningful reduction in the risk of disease recurrence or death compared to KEYTRUDA monotherapy in stage III/IV melanoma patients with high risk of recurrence following complete resection
•mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.31-1.08]; one-sided p-value=0.0266) compared with KEYTRUDA alone. Adverse events observed with mRNA-4157/V940 in KEYNOTE-942 were consistent with those previously reported in a Phase 1 clinical trial
•Results are the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial
•Companies plan to discuss results with regulatory authorities and initiate a Phase 3 study in melanoma in 2023 and to rapidly expand to additional tumor types
Rare disease vaccine: Propionic acidemia
•Phase 1/2, multiple ascending dose Paramount study of propionic acidemia (PA) candidate (mRNA-3927) is ongoing
•As of last clinical update (September 8th, Moderna R&D Day)
◦6 patient-years of experience on drug with all eligible participants electing to continue on Open Label Extension study
◦Encouraging data showed a decrease in the number of metabolic decompensation events (MDEs); initial discussions with regulators supportive of MDE as a primary endpoint for a pivotal study
Cardiovascular: Relaxin
•First patients have been dosed in a Phase 1B trial of our heart failure treatment candidate, mRNA-0184. This first-in-human Phase 1B clinical trial is being conducted in patients with stable heart failure to evaluate its safety and tolerability, and to assess the pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of a range of dose levels and dose intervals of mRNA-0184
•mRNA-0184 encodes for relaxin, a naturally occurring hormone that is known to cause hemodynamic changes that are potentially beneficial for heart failure patients. The mRNA sequence of mRNA-0184 is engineered to instruct the body to produce relaxin with an extended half-life, with the goal of producing a sustained clinical benefit in heart failure patients – this longer half-life may result in more durable effects compared to previous approaches
•mRNA-0184 utilizes similar technology as our propionic acidemia candidate, mRNA-3927
nhaled pulmonary therapeutics
Cystic fibrosis (CF)
•Moderna’s collaborator, Vertex Pharmaceuticals, announced that the U.S. Food and Drug Administration cleared its Investigational New Drug (IND) application for VX-522, an mRNA targeted at treating the underlying cause of cystic fibrosis for the approximately 5,000 people with CF who cannot benefit from a cystic fibrosis transmembrane conductance regulator (CFTR) modulator
•VX-522 is delivered to the lung through inhalation of a CFTR mRNA encapsulated by a lipid nanoparticle. Once delivered to the target lung cells, the mRNA is designed to produce functional copies of the CFTR protein
Summary of Corporate Updates
Reinvestments
•Moderna increases investments in R&D, manufacturing infrastructure, and company buildout, and pursues external investment opportunities (licenses and/or M&A). R&D investments in 2023 are estimated at $4.5 billion, up from approximately $3.3 billion (unaudited) for 2022
•Moderna has entered into an agreement to acquire OriCiro Genomics, a Japanese company with a novel development approach for cell-free synthesis and amplification of plasmid DNA, a key building block of mRNA manufacturing
•Moderna forms strategic research collaboration with CytomX Therapeutics for development of mRNA-based conditionally activated therapeutics for oncology and non-oncology conditions. CytomX will receive an upfront payment of $35 million, including $5 million of pre-paid research funding
•Ongoing strategic collaborations include a partnership with Carisma Therapeutics to discover, develop and commercialize in vivo engineered chimeric antigen receptor monocyte (CAR-M) therapeutics for the treatment of cancer. Additionally, Moderna is partnering with Metagenomi to accelerate the development of in vivo gene editing therapeutics
Return capital to shareholders
•Repurchased 23 million shares (avg. price $143/share) for $3.3 billion in 2022, with $2.8 billion remaining for future repurchases from the $3.0 billion August authorization
PRV
•Moderna has purchased a Priority Review Voucher (PRV), which allows the Company to obtain expedited FDA review of a licensing application. Moderna had previously been granted a PRV for mRNA-1273 and intends to use both PRVs to accelerate review of two expected BLA filings from our pipeline