Prof Guy and Prof Peng
Dr. R. Kip Guy obtained his BA in chemistry from Reed College, worked as a process development chemist at IBM, & received his PhD from the Scripps Research Institute. He held an Office of Naval Research Graduate Research Fellowship, George Hewitt Medical Research Fellowship, ACS Organic Division Fellowship, and a Helen Hay Whitney Postdoctoral Fellowship at UT Southwestern Medical Center. He was elected a Fellow of the American Association of the Advancement of Science and in 2023 he won the Phil Portoghese Award for Medicinal Chemistry from the ACS. He is the author of 202 papers and book chapters, and the inventor on 27 issued patents.
His presentation on Thursday 9th of May 2024 was titled:
Discovery and Early Development of SJ733 an ATP4 inhibitor
The dihydroisoquinolones (DHIQ’s), a novel class of antimalarials, were discovered using a phenotypic whole cell screen of erythrocytic co-cultures of malaria. A consortium of researchers in the academic, for-profit, and non-profit sectors developed the dihydroisoquinolone clinical candidate SJ733. In preclinical studies, SJ733 had good potency in vitro and in vivo and a fast rate of kill in vivo; was highly orally bioavailable in mice, rats, and dogs; and had mild toxicology in vivo. SJ733 targets ATP4, a sodium-proton antiporter critical for parasite viability in the blood stages and for gametocyte development. Phase la clinical studies with SJ733 revealed no serious adverse events or dose limiting toxicities; good oral bioavailability, and terminal half-life of 19 hours. Phase 1b studies in the P. falciparum human challenge model showed a fast parasite kill but strongly suggested that curing patients would require at least a 3-day schedule, due to metabolism by CYP3A4. A recently completed Phase 2a trial in Peru demonstrated that SJ733 monotherapy effectively cured blood stage P. vivax malaria. This study strongly suggests SJ733 is well positioned to be a fast-acting component in a combination drug for treating malaria.
His presentation on Thursday 10th of May 2024 was titled:
Glorious Failure: How to Bring a New Drug to Market
Drugs that address an unmet medical need have an enormous positive impact on society: introducing antibiotics and vaccines to common use in the middle 20th century shifted the life expectancy in the United States from 47 to 78 years and removed infectious disease as the major cause of death. Despite this enormous benefit, bringing new drugs to market remains arduous. Why is this the case? One cause is that we falsely perceive drug discovery as a gradual, incremental process and attempt to improve success rates by engineering and applying overwhelming force. Yet drug discovery is highly dependent on innovation, which occurs randomly and can be capitalized up on by prepared teams. We will discuss a route to success built on viewing the path as constituted by punctuated equilibria and pursuing drugs with small, agile, and resilient teams who learn from failures and rapidly respond to changes.