>>Hello everybody. I am Toshihiko Nishimura from Stanford. University is there to TTT out here, super aging, global OMIM global transportation group about infections, uh, or major point of concerns. In addition, this year, we have the COVID-19 pandemic. As you can see here, while the why the new COVID-19 patients are still increasing, meanwhile, case count per day in the United state, uh, beginning to decrease this pandemic has changed our daily life to digital transformation. Even today, the micro segmentation is being conducted online and doctor and the nurse care, uh, now increase to telemedicine. Likewise, the drug development process is in need of major change paradigm shift, especially in vaccine in drug development for COVID-19 is, should be safe, effective, and faster >>In the >>Anastasia department, which is the biggest department in school of medicine. We have Stanford, a love for drug device development, regulatory science. So cold. Say the DDT RDS chairman is Ron Paul and this love leaderships are long mysel and stable shaper. In the drug development. We have three major pains, one exceedingly long duration that just 20 years huge budget, very low success rate general overview in the drug development. There are Discoverly but clinical clinical stage, as you see here, Tang. Yes. In clinical stage where we sit, say, what are the programs in D D D R S in each stages or mix program? Single cell programs, big data machine learning, deep learning, AI mathematics, statistics programs, humanized animal, the program SNS program engineering program. And we have annual symposium. Today's the, my talk, I do like to explain limitation of my science significance of humanized. My science out of separate out a program. I focused on humanized program. I believe this program is potent game changer for drug development mouse. When we think of animal experiment, many people think of immediately mouse. We have more than 30 kinds of inbred while the type such as chief 57, black KK yarrow, barber C white and so on using QA QC defined. Why did the type mice 18 of them gave him only one intervention using mouse, genomics analyzed, computational genetics. And then we succeeded to pick up fish one single gene in a week. >>We have another category of gene manipulated, mice transgenic, no clout, no Kamal's group. So far registered 40,000 kind as over today. Pretty critical requirement. Wrong FDA PMDA negative three sites are based on arteries. Two kinds of animal models, showing safety efficacy, combination of two animals and motel our mouse and the swine mouse and non-human primate. And so on mouse. Oh, Barry popular. Why? Because mouse are small enough, easy to handle big database we had and cost effective. However, it calls that low success rate. Why >>It, this issue speculation, low success rate came from a gap between preclinical the POC and the POC couldn't stay. Father divided into phase one. Phase two has the city FDA unsolved to our question. Speculation in nature biology using 7,372 new submissions, they found a 68 significant cradle out crazy too, to study approved by the process. And in total 90 per cent Radia in the clinical stages. What we can surmise from this study, FDA confirmed is that the big discrepancy between POC and clinical POC in another ward, any amount of data well, Ms. Representative for human, this nature bio report impacted our work significantly. >>What is a solution for this discrepancy? FDA standards require the people data from two species. One species is usually mice, but if the reported 90% in a preclinical data, then huge discrepancy between pretty critical POC in clinical POC. Our interpretation is data from mice, sometime representative, actually mice, and the humor of different especially immune system and the diva mice liver enzyme are missing, which human Liba has. This is one huge issue to be taught to overcome this problem. We started humanized mice program. What kind of human animals? We created one humanized, immune mice. The other is human eyes, DBA, mice. What is the definition of a humanized mice? They should have human gene or human cells or human tissues or human organs. Well, let me share one preclinical stages. Example of a humanized mouse that is polio receptor mice. This problem led by who was my mentor? Polio virus. Well, polio virus vaccine usually required no human primate to test in 13 years, collaboration with the FDA w H O polio eradication program. Finally FDA well as w H O R Purdue due to the place no human primate test to transgenic PVL. This is three. Our principle led by loss around the botch >>To move before this humanized mouse program, we need two other bonds donut outside your science, as well as the CPN mouse science >>human hormone, like GM CSF, Whoah, GCSF producing or human cytokine. those producing emoji mice are required in the long run. Two maintain human cells in their body under generation here, South the generation here, Dr. already created more than 100 kinds based on Z. The 100 kinds of Noe mice, we succeeded to create the human immune mice led the blood. The cell quite about the cell platelets are beautifully constituted in an mice, human and rebar MAs also succeeded to create using deparent human base. We have AGN diva, humanized mouse, American African human nine-thirty by mice co-case kitchen, humanized mice. These are Hennessy humanized, the immune and rebar model. On the other hand, we created disease rebar human either must to one example, congenital Liba disease, our guidance Schindel on patient model. >>The other model, we have infectious DDS and Waddell council Modell and GVH Modell. And so on creature stage or phase can a human itemize apply. Our objective is any stage. Any phase would be to, to propose. We propose experiment, pose a compound, which showed a huge discrepancy between. If Y you show the huge discrepancy, if Y is lucrative analog and the potent anti hepatitis B candidate in that predict clinical stage, it didn't show any toxicity in mice got dark and no human primate. On the other hand, weighing into clinical stage and crazy to October 15, salvage, five of people died and other 10 the show to very severe condition. >>Is that the reason why Nicole traditional the mice model is that throughout this, another mice Modell did not predict this severe side outcome. Why Zack humanized mouse, the Debar Modell demonstrate itself? Yes. Within few days that chemistry data and the puzzle physiology data phase two and phase the city requires huge number of a human subject. For example, COVID-19 vaccine development by Pfizer, AstraZeneca Moderna today, they are sample size are Southeast thousand vaccine development for COVID-19. She Novak UConn in China books for the us Erica Jones on the Johnson in unite United Kingdom. Well, there are now no box us Osaka Osaka, university hundred Japan. They are already in phase two industry discovery and predict clinical and regulatory stage foster in-app. However, clinical stage is a studious role because that phases required hugely number or the human subject 9,000 to 30,000. Even my conclusion, a humanized mouse model shortens the duration of drug development humanize, and most Isabel, uh, can be increase the success rate of drug development. Thank you for Ron Paul and to Steven YALI pelt at Stanford and and his team and or other colleagues. Thank you for listening.