Moderna Expands its mRNA Pipeline with Three New Development Programs

Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced that it is expanding its mRNA pipeline with three new development programs. This announcement reflects the Company’s commitment to expanding its portfolio building on Moderna’s experience with Spikevax^®, its COVID-19 vaccine. The development programs announced today are mRNA vaccine candidates against herpes simplex virus (HSV), varicella-zoster virus (VSV) to reduce the rate of shingles and a new checkpoint cancer vaccine. HSV and VZV are latent viruses that remain in the body for life after infection and can lead to life-long medical conditions. Moderna now has five vaccine candidates against latent viruses in development, including against cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human immunodeficiency virus (HIV), HSV and VZV.

“We are pleased to announce these new development programs, which reflect the continued productivity of our platform and the potential of our mRNA technology to impact the lives of hundreds of millions of people,” said Stéphane Bancel, Chief Executive Officer of Moderna. “We are committed to addressing latent viruses with the goal of preventing the lifelong medical conditions that they cause with our mRNA vaccine programs. With our HSV and VZV vaccine candidates, we also hope to improve the quality of life for those with symptomatic disease. With our new checkpoint cancer vaccine, we look forward to exploring if we can induce T cells specific to PD-L1 and IDO1 through vaccination. Our research teams are working on additional mRNA candidates, which we look forward to sharing in the future.”

Herpes simplex virus (HSV) vaccine candidate (mRNA-1608)

Moderna’s herpes simplex virus (HSV) vaccine candidate (mRNA-1608) is a vaccine candidate against HSV-2 disease. Moderna expects that an HSV-2 vaccine could provide cross-protection against HSV-1. With mRNA-1608, the Company aims to induce strong antibody response with neutralizing and effector functionality combined with cell-mediated immunity. There is no vaccine approved against HSV.

Herpes simplex viruses (commonly known as herpes) are categorized into two types: HSV-1 infects the mouth, face and genitals, and HSV-2 primarily infects the genitals. Both viruses establish lifelong latent infections within nearby sensory neurons from which they can reactivate and re-infect the skin. There is a significant burden of disease from HSV genital infections. Diagnosed, symptomatic genital herpes causes a reduction in quality of life, which antivirals (current standard of care) only partially restore. In the U.S., approximately 18.6 million adults ages 18 to 49 years are living with HSV-2. Globally, approximately 5% of the population in the 18-to-49-year age range is HSV-2 seropositive. Moderna expects that an HSV vaccine could deliver similar efficacy as suppressive antiviral treatment and would likely improve compliance and quality of life.

Varicella-zoster virus (VZV) vaccine candidate (mRNA-1468)

Moderna’s varicella-zoster virus (VZV) vaccine candidate (mRNA-1468) is designed to express varicella-zoster virus (VZV) glycoprotein E (gE) to reduce the rate of shingles (herpes zoster). Shingles occurs in one of three adults in their lifetime and incidence dramatically increases at approximately 50 years of age. Declining immunity in older adults decreases immunity against VZV, allowing reactivation of the virus from latently infected neurons, causing painful and itchy lesions. Moderna has published preclinical data on an mRNA vaccine encoding the VZV gE antigen.

VZV causes shingles. Serious herpes zoster complications include postherpetic neuralgia (10-13% of herpes zoster cases), bacterial coinfections, and cranial and peripheral palsies; 1-4% of HZ cases are hospitalized for complications. Severity of disease and likelihood of complications, including postherpetic neuralgia (PHN) also increases with age. Immunocompromised patients, autoimmune disease patients using immunosuppressive therapies, HIV-infected patients, hematopoietic stem cell (HSCT) and organ transplant recipients have an increased risk of developing herpes zoster. The incidence of herpes zoster has been increasing throughout the world from 0.76 per 1000 person years from 1945 to 1949, to 7.2 per 1000 person years in 2016.

Checkpoint cancer vaccine (mRNA-4359)

Moderna’s new checkpoint cancer vaccine candidate (mRNA-4359) expresses Indoleamine-dioxygenase (IDO) and programmed death-ligand 1 (PD-L1) antigens. Moderna designed mRNA-4359 with the goal of stimulating effector T-cells that target and kill suppressive immune and tumor cells that express target antigens. Moderna is planning to explore initial indications for advanced or metastatic cutaneous melanoma and non-small cell lung carcinoma (NSCLC).

Melanoma is the fifth most common cancer diagnosis in the U.S. It accounts for 5.3% of all new cancer diagnoses and 1.5% of all cancer-related deaths. Cutaneous melanoma is a cancer that starts in the melanocytes (pigment-producing cells) of the skin. If diagnosed at the local stage, the 5-year survival rate is approximately 95%. However, for regional or metastatic disease (stage IIIB+), 5-year survival rates decline to approximately 30 to 60%. Approximately 18,000 new patients are diagnosed with stage IIIB+ cutaneous melanoma in the U.S. Advanced melanoma, a rare and serious type of skin cancer, is responsible for most skin cancer-related deaths, despite representing only 1% of skin cancer cases. Current standard of care pembrolizumab, nivolumab or the combination of nivolumab + ipilimumab.

NSCLC frequently goes undetected, remaining asymptomatic until it has progressed to later stages. Approximately, 115,000 people are diagnosed with metastatic NSCLC or progress to metastatic disease annually in the U.S. The current approach to treatment of metastatic NSCLC treatment is dependent on the presence of PD-L1 expression. If tumor PD-L1 expression is greater than 50% pembrolizumab or atezolizumab monotherapy are preferred, while a combination of chemotherapy and pembrolizumab is preferred for patients with PD-L1 expression less than 50%.