OVERALL – ABSTRACT Pandemic prevention and preparedness is a major scientific and societal priority that requires sustained and forward looking investments across governmental, non-governmental, academic and private sectors to develop an arsenal of countermeasures against the existential threat of viral pandemics. Combining world-leading BSL3/4 capabilities at University of Texas of Medical Branch (UTMB) and state-of-the art drug discovery technologies at Novartis, the UTMB Novartis Alliance for Pandemic Preparedness (UNAPP), is a unique and innovative partnership that brings together the multi-disciplinary expertise required to deliver high quality antiviral drug candidates. Enabled by world-leading virologists and seasoned drug hunters, UNAPP will aggressively prosecute a portfolio of 5 projects aiming to discover orally available, safe, and effective drugs against coronaviruses, flavivirus and henipavirus, three major classes of viruses with pandemic potential. The projects portfolio combines approaches targeting well validated drug targets, such as the RNA- dependent RNA polymerases and viral proteases, as well as phenotypic screening, which will allow for the discovery of clinical drug candidates and novel targets that will advance our fundamental understanding of the biology of those viruses. Four scientific Cores—Virology, High-Throughput Biology, Drug Discovery and Translational Research Cores—will provide technological and scientific expertise to support Project Teams and implement the scientific strategy toward novel antiviral drugs. The UNAPP will be governed by an Administrative Core which will be co-led by the PIs, Dr. Pei-Yong Shi and Dr. Thierry Diagana, who have a long track-record of successfully working together. Both PIs have led multiple productive collaborations focused on translational impact and combining public, private and non-governmental organizations. The Administrative Core will provide integrated decision making in scientific, operational, financial, intellectual property protection, and communication. In collaboration with all project and Core leaders, as well as with external input from a Scientific Advisory Board and NIH program officers, they will ensure that the projects portfolio leverages the full spectrum of technologies and capabilities residing in all four scientific Cores, capturing synergies across projects through cross-learning and efficient deployment of platforms relevant to multiple viruses. Because of the unique complementarity of the scientific Cores and the remarkable synergies of the project portfolio, we fully expect that the UNAPP will yield exceptional productivity and deliver all the proposed objectives: (1) Deliver 3 IND-ready candidates and 3 Development Candidates, (2) advance antiviral research, and (3) train next-generation drug hunters.

OVERALL – PUBLIC HEALTH RELEVANCE Pandemic preparedness is a major scientific and societal priority that requires sustained and forward-looking investments across governmental, non-governmental, academic, and private sectors. Combining world-leading virology and BSL3/4 capabilities at University of Texas of Medical Branch (UTMB) and state-of-the-art drug discovery technologies at Novartis, the UTMB-Novartis Alliance for Pandemic Preparedness (UNAPP) brings together the multi-disciplinary expertise required to deliver high quality antiviral drug candidates. UNAPP will prosecute a portfolio of 5 projects aiming to discover orally available, safe, and effective drugs against coronaviruses, flaviviruses, and henipaviruses, three major classes of viruses with pandemic potential. We will (i) deliver 3 IND-ready candidates and 3 Development Candidates, (ii) advance antiviral research, and (iii) train the next-generation of drug hunters.