Notes from Moderna’s (NASDAQ:MRNA) R&D Day event:
COVID-19 vaccine mRNA-1273 represents a 3-4-year accelerator to commercial status. Encodes for the full spike protein of SARS-CoV-2. Phase 1 study (led by NIH): Three dose levels assessed (25, 100, 250 microgram). 250 dose eliminated due to increased reactogenicity. Three age cohorts: 18-55, 56-70 and 71+. Binding antibody levels consistent across age groups, all above convalescent sera at day 43 (vaccine dosed on day 1 & 29) (100 microgram dose). Neutralizing antibody titers on par with upper levels of convalescent sera. Th1-biased CD4 T cell responses consistent across age groups. Phase 2 study: 50 and 100 microgram doses being tested in people 18 to less than 55 years old and 55+. Fully enrolled (n=600). Primary endpoint is safety. All subjects will be followed for 13 months (12 months after second dose). Phase 3 study: 100 microgram dose in people at least 65 years old, less that 65 at increased risk of COVID-19 complications (both represent 25-40% of enrollment) and less than 65 not at risk of complications (60-75% of enrollment). Subjects will be followed for ~two years after the second dose. Almost 10K subjects have received the second dose. Independent Data and Safety Monitoring Board to review unblinded results.
Pipeline status: 1 Phase 3 program, 4 Phase 2s and 18 early-stage (Phase 1 or preclinical). Cash balance: $3.1B as of end of June.
CEO Bancel says mRNA platform most advanced compared to competitors.
CMV vaccine (mRNA-1647) showed positive effect in Phase 2 study. Phase 3 to start in 2021.
Plans to enter seasonal flu business (type A and type B). Planning to develop a COVID-19/influenza combo vaccine for the elderly.
Cited expanded Vertex partnership in cystic fibrosis.
Cited Chiesi partnership in pulmonary arterial hypertension.
Antibody against Chikungunya virus (mRNA-1944) advancing to Phase 2. The actual therapy encodes for heavy and light chains of CHKV-24 antibody which may confer passive immunity. A few Grade 3 (serious) adverse events were observed at the 0.6 mg/kg dose in a Phase 1 study. Two doses of 0.3 mg/kg a week apart is the planned regimen. Two-dose approach produced neutralizing antibody levels above the single 0.6 mg/kg dose with a better safety profile.
Rare organic acidemias are being explored. Propionic acidemia program, mRNA -3927, has Fast Track, Orphan Drug and Rare Pediatric Disease designations. Extension study to launch contingent on a favorable risk/benefit profile from Phase 1/2 study. Methylmalonic acidemia (mRNA-3705): trial paused due to COVID-19. Improved trial design and plan to bring a next-gen product forward (improved pharmacology). IND and CTA applications next up.
Cancer vaccines, mRNA-4157 and mRNA-5671, being developed with Merck (combined with Keytruda).
Intratumoral programs: mRNA-2416 and mRNA-2752. MEDI1191 being developed with AstraZeneca.
2416 encodes a protein called OX40L that enhances immune response to the tumor. Phase 1/2 study, combined with durvalumab [AstraZeneca’s Imfinzi], fully enrolled.
2752 encodes OX40L, IL-23 and IL-35y. PD-L1 expression increased after treatment with 2752.
Prophylactic vaccines:
CMV (mRNA-1647): Infection can be serious for developing fetus. Leading cause of birth defects in newborns. Vaccine includes 6 mRNAs, 5 enode pentamer, 6th the gB antigen. Should elicit a stronger immune response. Three-month interim data from Phase 2 study based on 65% of enrollees (due to COVID-19 disruptions). Safety: injection pain was the most common local adverse event (AR). Most common systemic ARs were headache, fatigue and myalgia (muscle pain). Robust increases in neutralizing antibody titers observed in both seropositive and seronegative participants. Enrollment to be increased to generate stronger safety profile at 100 microgram dose level.
Combo vaccine hMPV/PIV3 (mRNA-1653). Phase 1b ongoing in adults and children.
RSV vaccine (mRNA-1345): IND opened last month.
Terry Nolan, M.D., Ph.D. from Melbourne, Australia: Overview of pediatric vaccines. Multiple mRNA combo vaccines offer a range of advantages (tunable, reduced adjuvant exposure, capacity to package for multiple disease targets, reduced risk of chemical/immunologic interference). Regulators don’t like adjuvants due to increased complexity.
https://seekingalpha.com/news/3614900-moderna-highlights-pipeline-programs-r-and-d-day
