Marking its 100th anniversary, Yuhan is overhauling its research and development (R&D) organization and new drug development strategy. The plan is to move beyond simply developing candidate substances (pipelines) for technology out-licensing and transform into a new drug development system based on global co-development, artificial intelligence (AI), and targeted protein degradation (TPD) platforms.
On the 28th at Yuhan headquarters in Dongjak District, Seoul, R&D President Kim Yeol-hong and Central Research Institute Director Choi Young-gi said they are changing the way the organization is run along with a next-generation pipeline strategy focused on oncology, obesity, immunology, and metabolic diseases, and are also building new technology platforms.
◇ Expanding risk-sharing and combination therapy development
The most striking change is the "co-investment and co-development" strategy. Yuhan plans co-investment and co-development with global pharmaceutical companies and investors and, if needed, will even set up a separate corporation (NewCo) to share risk and revenue.
Kim said, "Recently, global companies are moving not to simply license in, but to establish separate companies, conduct co-investment and co-operations, and then acquire them as the clinical stage advances," adding, "As R&D expense grows, structures that share risk and split profits upon success have become the global trend."
Kim said, "Yuhan's annual R&D investment is about 250 billion won, and about 150 billion won of that goes solely to global innovative new drug development," adding, "It is realistically burdensome to develop all current pipelines through late-stage clinical trials and phase 3 with our own expense."
To that end, Yuhan said it is strengthening its global business development (BD) organization around its U.S. corporation, Yuhan USA. Kim said, "In the past, NewCo setups were centered on overseas venture capital or global capital, but recently domestic capital is also actively participating."
Kim also mentioned the cases of Regeneron, a U.S. biotech company, and BeiGene, now called BiOne Medison, a Nasdaq-listed China-based company that recently changed its place of incorporation to Switzerland.
Both corporations secured their own pipelines (new drug candidates) needed for combination therapy strategies in oncology at the same time and grew into global pharmaceutical companies.
Kim emphasized, "To rise to the level of global companies, it is important to build in parallel the in-house pipelines needed for combination strategies," adding, "I believe the only domestic company with such a lineup is Yuhan."
The way the organization is run is also changing. Yuhan recently established an SAB (Scientific Advisory Board). Fourteen advisors have been appointed so far, and their names are disclosed on the website.
Kim said, "The goal is to aggregate experts' opinions to push successful development and even reflect feedback from clinical settings where the drug will actually be used," adding, "We are setting R&D investment priorities based on systematic progress management and evaluation."
He continued, "In the past, considering researchers' effort and dedication sometimes made us hesitate to halt less competitive projects," adding, "We now have a system that enables bolder and more objective decisions based on external expert evaluations."
The research direction has changed as well. Whereas development used to focus on "best-in-class" drugs that improved efficacy or safety over competitors, it is now shifting toward "first-in-class" new drugs with mechanisms of action not seen before and toward platform technologies.
◇ "We will hit targets drugs couldn't before"… strengthening TPD and AI strategies
In particular, Yuhan put forward targeted protein degradation (TPD) technology as a core next-generation pillar. Unlike existing drugs that only inhibit the function of disease-causing proteins, TPD is a next-generation new drug technology that degrades and removes the proteins themselves inside cells. Because it can reach proteins that were hard to tackle with existing drugs, it is drawing attention in the global pharmaceutical industry as a next-generation platform technology.
Yuhan has formed a dedicated TPD team, and its first project has been proposed and is preparing to start development. It is particularly focusing on next-generation approaches that overcome the limits of the conventional PROTAC method.
Central Research Institute Director Choi said, "Early TPD centered on the PROTAC method with a 'bifunctional' structure that links two proteins," adding, "But the large molecular size can hinder absorption in the body, make oral (by mouth) drug development difficult, and limit delivery to specific tissues such as the brain."
He continued, "Recently, 'molecular glue degraders' that use small molecules to link disease proteins with the intracellular degradation system and remove target proteins have drawn attention as next-generation technology," adding, "We are developing technology that can reach even 'undruggable' targets once thought impossible to make into medicines." He said, "We expect meaningful results within a few years."
Yuhan is also building an AI-based new drug development platform, Yu-NIVUS. The key is to automate the DMTA (Design-Make-Test-Analyze) cycle that connects candidate design, synthesis, activity prediction, and optimization using AI. Choi said, "The step-by-step functions are already being applied to real projects," adding, "Next year we plan to build an optimization system that automates the entire process."
Behind Yuhan's simultaneous changes in organization and strategy lies the question of what comes after Leclaza, a lung cancer treatment that succeeded in development and commercialization. The strategy is to grow into a global pharmaceutical company that continuously creates new drugs based on global commercialization experience. Kim said, "We are not aiming for small markets like second line or third line," adding, "We will create a global blockbuster that can rise to the first-line standard-of-care market."