Moderna Announces Expansion of mRNA Research Across Respiratory, Oncology, Rare Disease Franchises

Moderna, Inc has announced new business and clinical updates across its franchises, specifically in the mRNA medicine space, including introducing several new programs, according to a statement from the company.1 Moderna presented a financial update and updates to expanding mRNA medicine, which include the respiratory franchise, latent and other viruses franchise, oncology franchise, and rare disease franchise.¹

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"Our mRNA platform is working. With today's positive phase 3 flu results, along with previous results in COVID(-19) and [respiratory syncytial virus (RSV)], we are now 3 for 3 on advancing respiratory disease programs to positive phase 3 data," Stéphane Bancel, CEO of Moderna, said in the company statement. "In the near term, we look forward to product launches in our oncology, latent, rare, and infectious disease franchises. In the fourth quarter of this year, we also expect to provide data on our next-generation COVID(-19) and flu combination, mRNA-1083, and additional efficacy analysis on our phase 2 INT study. With significant momentum across the business and our pipeline, we are excited by the near future and focused on execution."¹

Moderna has demonstrated potential clinical benefits in mRNA technology for cancer (mRNA-4157), in 3 rare diseases (mRNA-3705, mRNA-3927, mRNA-3745), and multiple infectious disease vaccines (mRNA-1273, mRNA-1345, mRNA-1010). Furthermore, the company has advanced 6 programs into late-stage development, including 2 approved or filed for approval and 3 more that have completed phase 3 enrollment. Moderna expects to double the number of programs by 2025 and launch up to 15 products in 5 years across cancer, rare disease, and infectious disease spaces, with up to 4 of those launches coming by 2025.¹

Updates in Respiratory Franchise

The respiratory franchise is targeting an approximately $30 billion annual market, broken down into $15 billion for the COVID-19 market, $10 billion for the RSV market, and $6 million for the influenza market. The company reports that there is a potential growth with more effective vaccines.¹

Furthermore, respiratory product sales in 2027 are expected to be approximately $8 billion to $15 billion, depending on vaccination rates, efficacy, and the company’s market share.¹

COVID-19 Vaccine Update

Moderna reported that the monovalent XBB.1.5 vaccine, mRNA-1273.815, demonstrated potent neutralization and cross-reactivity. The vaccine also had similar neutralizing responses as XBB.1.5, XBB.1.16, and XBB.2.3.2 sub-variants. The results demonstrate that mRNA-1273.815 elicited an 8.7 to 11-fold increase in neutralizing antibodies against BA.2.86, EG.5, and FL.1.5.1.¹

On September 11, 2023, the FDA approved updated formulations of Moderna’s COVID-19 vaccine for emergency use due to its ability to target current circulating variants for those aged 12 years and older and received Emergency Use Authorization for those aged 6 months to 11 years.²

Seasonal Influenza Vaccine Update

The mRNA-1010 vaccine has demonstrated an acceptable safety and tolerability profile across all clinical trials to date, which included the phase 3 trials P301 (NCT05415462), P302 (NCT05566639), and P303 (NCT05827978).¹

Enrollment is also complete for P303, which will investigate the safety and immunogenicity for the updated formulation of mRNA-1010. The interim analysis has demonstrated that the vaccine met all co-primary endpoints across all 4 A and B strains, with higher HAI geometric mean titers and seroconversions compared to Fluarix. Investigators also observed improved immunogenicity in all age groups, including older adults.¹

RSV Vaccine Update

Moderna has submitted mRNA-1345 for marketing authorization applications globally for the prevention of RSV-associated lower respiratory tract disease and acute respiratory disease in adults aged 60 years or older. Additionally, the company filed for a biologics license application with the FDA under priority review. Regulatory applications were also submitted in Europe, Switzerland, Australia, Canada, and the United Kingdom.¹

The submissions were based on positive data from the ConquerRSV study (NCT05127434), demonstrating a vaccine efficacy of 83.7% for 2 or more symptoms and 82.4% for 3 or more symptoms. The vaccine was also well tolerated with a favorable safety profile.³

Combination Respiratory Vaccines Update

The enrollment for 4 combination trials is now complete, including:¹

• Flu/COVID-19 phase 1/2 for mRNA-1073, a mix of mRNA-1010 and mRNA-1273
• Flu/RSV phase 1 for mRNA-1045, a mix of mRNA-1010 and mRNA-1345
• Flu/COVID-19/RSV phase 1 for mRNA-1230, a mix of mRNA-1010, mRNA-1273, and mRNA-1345
• Flu/COVID-19 phase 1/2 for mRNA-1083, a mix of mRNA-1010 and mRNA-1283

Moderna intends to have the combination vaccines available as early as 2024, with regular updates to the combinations when appropriate.¹

Latent and Other Viruses Franchise

The company is also developing vaccines against 6 latent and other viruses, including cytomegalovirus (CMV), Epstein Barr virus, herpes simplex virus, varicella zoster virus, norovirus, and HIV. The CMV vaccine, mRNA-1647, is currently in a fully enrolled phase 3 study. The trial will evaluate the efficacy, safety, and immunogenicity the vaccine in the prevention of infection in women of childbearing age.¹

Additionally, Moderna will also develop 2 multi-valent virus-like particle vaccines, mRNAa-1403, a trivalent vaccine, and mRNA-1405, a pentavalent vaccine, for the prevention of acute gastroenteritis, the most prevalent norovirus genotypes, in young children and older adults.¹

Oncology Franchise

The updates for the oncology franchise include a individualized neoantigen therapy being developed with Merck. It also includes the checkpoint and triplet vaccines.¹

Individualized Neoantigen Therapy Update

The phase 2b KEYNOTE-942/mRNA-4157-P201 trial (NCT03897881) evaluated mRNA-4157, an individualized neoantigen therapy, in combination with pembrolizumab (Keytruda; Merck) for patients with stage 3 or 4 resected high-risk melanoma.^1,4 Investigators of the study found that the combination significantly prolonged recurrence-free survival compared to pembrolizumab alone.Additionally, the results demonstrated that the combination reduced the risk of death by 44% compared to the monotherapy.⁴

Moderna expects to provide additional data from the study in the fourth quarter.¹

Furthermore, the companies announced the initiation of the phase 3 study V940-001, which will evaluate the safety and efficacy of mRNA-4157 with pembrolizumab for individuals with stage 2B through 4 resected high-risk melanoma. They will also partner for an upcoming phase 3 trial for individuals with stage 2 through 3B non–small cell lung cancer (NSCLC) who have received adjuvant chemotherapy with no recurrence. This trial is intended to launch later this year, with the companies planning to expand the development program to additional tumor types.¹

Checkpoint Vaccine Update

mRNA-4359, Moderna’s checkpoint vaccine, is being evaluated in an ongoing phase 1/2 study as a monotherapy and in combination with pembrolizumab. The tumors that will be evaluated include cutaneous melanoma, NSCLC, non-muscle invasive bladder cancer, head and neck squamous cell carcinoma, microsatellite stable colorectal cancer, basal cell carcinoma, and triple-negative breast cancer, according to the statement from Moderna.¹

Triplet Update

mRNA-2752, Moderna’s triplet vaccine, is currently in an ongoing phase 1 study to evaluate the safety and tolerability of the vaccine alone and with durvalumab. Additionally, another ongoing study evaluating the vaccine in patients with ductal carcinoma in situ is currently enrolling individuals for a monotherapy.¹

Rare Disease Franchise

In the statement, Moderna notes that its disease portfolio, including therapies for methylmalonic (MMA), propionic acidemia (PA), glycogen storage disease (GSD1A), and phenylketonuria (PKU) could represent a $10 billion market and address significant unmet needs. The company expects to launch 4 rare disease products in the next 5 years.¹

MMA

In a phase 1/2 study, 11 individuals have been administered mRNA-3705, totaling 221 doses. All individuals in the study opted to stay in the open-label extension. Current data show that mRNA-3705 has been generally well-tolerated with no discontinuations due to safety or dose-limiting toxicities.¹

Currently, the early results indicate potential decreases in annualized metabolic decompensation events, frequency, and MMA-related hospitalizations for individuals treated with mRNA-3705 when compared to pre-treatment.¹

PA

A global phase 1/2 trial is currently enrolling individuals in a dose confirmation arm of mRNA-3927, in which 16 individuals have been dosed with more than 280 doses and 12 individuals have received more than 1 year of dosing. As of current data, the treatment has been generally well-tolerated with no discontinuations related to safety or dose-limiting toxicities.¹

The enrollment is ongoing, with all individuals who have completed the treatment in the main study opting to enter the long-term extension study.¹

PKU

Moderna has also opened an investigational new drug application for mRNA-3210, an mRNA that encodes the phenylalanine hydroxylase enzyme in the lipid-based nanoparticles used in both the MMA and PA development candidates.¹

Financial Update

Lastly, Moderna has reported a financial update. The company expects to add $10 billion to $15 billion in annual sales 5 years after launching their new oncology and rare and latent disease products by 2028. This is in addition to the previously announced expected sales from the respiratory franchise in 2027.¹

Moderna will also be investing approximately $25 billion in research and development from 2024 through 2028. The sales expected from COVID-19 in 2023 are expected to be $6 billion to $8 billion, dependent on the vaccination rates.¹

Reference

1. Moderna expands the field of mRNA medicine with positive clinical results across cancer, rare disease, and infectious disease. News release. Moderna. September 13, 2023. Accessed September 13, 2023. https://investors.modernatx.com/news/news-details/2023/Moderna-Expands-the-Field-of-mRNA-Medicine-with-Positive-Clinical-Results-Across-Cancer-Rare-Disease-and-Infectious-Disease/default.aspx#:~:text=Expanding%20the%20Field%20of%20mRNA%20Medicine&text=The%20Company%20has%20advanced%20a,1345%2C%20mRNA%2D1010
2. Gallagher A. FDA authorizes updated COVID-19 vaccine formulations for current variants. Pharmacy Times. September 11, 2023. Accessed September 14, 2023. https://www.pharmacytimes.com/view/fda-authorizes-updated-covid-19-vaccine-formulations-for-current-variants
3. Gallagher A. Moderna files regulatory submissions for mRNA-1345 vaccine against RSV lower respiratory tract disease. Pharmacy Times. July 6, 2023. Accessed September 14, 2023. https://www.pharmacytimes.com/view/moderna-files-regulatory-submissions-for-mrna-1345-vaccine-against-rsv-lower-respiratory-tract-disease
4. Hippensteele A. Personalize mRNA cancer vaccine with pembrolizumab significantly prolonged recurrence free survival in resected high-risk melanoma. Pharmacy Times. April 17, 2023. Accessed September 14, 2023. https://www.pharmacytimes.com/view/personalized-mrna-cancer-vaccine-with-pembrolizumab-significantly-prolonged-recurrence-free-survival-in-resected-high-risk-melanoma