Pam King Sams
Penn Medicine scientists are deeply engaged in the efforts to make vaccines for COVID-19.
Four of the leading candidates are based on Penn-developed intellectual property, and they are participating in several of the vaccine trials.
Two of the leading Phase 3 trials are modified RNA vaccines, those from Moderna and BioNtech working with Pfizer. Both are based on the work of Drew Weissman, MD, PhD, in Penn Medicine's Infectious Disease division, who discovered that chemical modifications of RNA can make the molecules more stable and can prevent a form of troublesome inflammation that results from the use of unmodified RNA.
Dr. Weissman also showed that modified RNA can be packaged in lipid nanoparticles for efficient delivery. His patents have been licensed by both Moderna and BioNtech, and thus far, both vaccines appear promising and may provide results from Phase 3 between October and the end of the year. (A note of caution, as RNA vaccines are relatively new, and have not been used before for large scale immunization, so the studies intended to identify rare-side effects are critical.)
Ultimately, with multiple vaccines headed toward potential use in the clinic, it will be critical to measure the immune response to each vaccine through deep immune profiling to understand which individuals are best suited for a given vaccine.
Funding for Penn Medicine’s vaccine work can help the team better assess each vaccine, ensure patients have robust immune protection, and study the longevity of successful immune response.
Below is a summary of Penn’s SARS-CoV-2 Vaccine Development Efforts – Summer 2020
Moderna SARS-CoV-2 vaccine (mRNA-1273)
• Lipid nanoparticle (LNP) encapsulated modified mRNA vaccine
• Uses Penn pseudouridine-modified mRNA technology (inventors: Drew Weissman / Katalin Kariko) for which Moderna has a sublicense.
• Penn was not involved in development of this vaccine candidate.
• Vaccine to enter Phase 3 clinical testing in July with an anticipated 30,000 subject enrollment
• Moderna partnered with Lonza for product manufacturing / commercial scale-up. Large scale manufacturing of the vaccine is going to proceed at risk concurrently with the registration trial. Moderna estimates being able to produce up to one billion doses in 2021.
BioNTech/Pfizer SARS-CoV-2 vaccine (BNT-162)
• Lipid nanoparticle (LNP) encapsulated mRNA vaccines
• Currently being tested in Phase 1 clinical trial.
• Trial study design involved three vaccine doses and testing of four separate vaccines / immunogen constructs.
• Penn was not involved in development of current BNT-162 vaccine products.
• Two of the four vaccine candidates tested in the Phase 1 trial use Penn’s pseudouridine-modified mRNA technology, one candidate uses unmodified mRNA and one candidate uses self-amplifying mRNA (replicase technology).
• BioNTech also has a sublicense to the Weissman/Kariko Penn IP covering pseudouridine-modified mRNA.
• A Phase 3 study may be initiated as early as July 2020.
• Commercial manufacturing being established at multiple sites by BioNTech and Pfizer. They also plan to proceed with large-scale manufacturing concurrently with Phase 3 trial and estimate being able to produce several hundred million vaccine doses in 2021.
Penn / Weissman Lab collaboration with Chulalongkorn University (Thailand)
• Collaboration agreement (CRA) between Penn and Chulalongkorn University for preclinical development of a modified mRNA vaccine for SARS-CoV-2.
o Penn/Weissman Lab producing mRNA vaccine candidate (mRNA + LNP) for preclinical evaluation. Penn also conducting certain immunogenicity assays.
o Animal testing (now in macaques) being conducted at Chulalongkorn University (Thailand).
• Government of Thailand supporting some of the work at Chulalongkorn University with the goal to produce a COVID-19 vaccine for Thailand and underserved countries in SE Asia.
• Chulalongkorn PI is Professor Kiat Ruxrungtham, M.D. (Professor of Medicine, Vice President for Research and Innovation, and Director of the Chula Vaccine Research Center).
Harvard/Penn SARS-CoV-2 vaccine (AAV 32.33)
• Multi-institutional R&D collaboration involving Mass Eye and Ear, Mass General Hospital, Penn/GTP, and Partners Healthcare.
• Project PIs are Luk Vandenberghe (MEEI), Mason Freeman (MGH), and Jim Wilson (Penn).
• Pre-clinical stage; IND enabling studies to be conducted at Penn
• Harvard leading project, development and corporate outreach
• Relies on AAV capsid technology invented at Penn and exclusively licensed to GSK and then exclusively sublicensed to REGENXBIO.
• Novartis/AveXis have indicated support for the initial GMP manufacturing of clinical grade material for upcoming human clinical trials.
Inovio / Weiner COVID-19 DNA vaccine (INO-4800)
• Inovio previously developed a DNA vaccine to a related coronavirus (MERS-CoV) (INO-4700) that was well tolerated and elicited antibody response in 95% of study participants in a Phase 1 study. Inovio is currently planning a Phase 2 trial for INO-4700 in the Middle East, where the largest MERS outbreaks have occurred to date.
• In June 2020, Inovio secured $71M from the US DOD to ramp up production of their INO-4800 vaccine for SARS-CoV-2. Goal is to be able to produce “hundreds of millions of doses in 2021.”
• Vaccine requires a handheld in vivo electroporation device to deliver the DNA vaccine to cells.
• Vaccine was developed using a DNA vaccine platform technology developed at Penn and licensed to Inovio.
• Phase 1 study data for SARS-Co-V vaccine INO-4800 to be announced this month.
• Penn was a trial site for the Phase 1 study. (Pablo Tebas, M.D. was the trial PI.)
• Phase 2/3 study to be initiated in Summer 2020. Study may be conducted in China and South Korea.
• Inovio estimates an ability to manufacture 1 million doses by end of 2020. They are actively identifying contract manufacturers to scale up commercial vaccine production levels.
Penn Active Participation in COVID-19 Vaccine Trial Network
• Penn participating in public-private partnership program launched by the NIH called ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines).
• See: https://www.nih.gov/news-events/news-releases/nih-launch-public-private-partnership-speed-covid-19-vaccine-treatment-options