Marking its 100th anniversary, Yuhan is overhauling its research and development (R&D) organization and new drug development strategy. It plans to move beyond simply developing candidates (pipelines) for licensing out and shift its constitution to a new drug development system based on global co-development, artificial intelligence (AI), and targeted protein degradation (TPD) platforms.
At R&D Day held on the 28th at Yuhan's headquarters in Dongjak District, Seoul, R&D President Kim Yeol-hong and Central Research Institute Director Choi Young-gi said they are changing how the organization operates and building new technology platforms alongside a next-generation pipeline strategy focused on oncology, obesity, immunology, and metabolic diseases.
◇ Expanding risk-sharing and combination therapy development
The most notable change is the "co-investment and co-development" strategy. It plans to pursue co-investment and co-development with global pharmaceutical companies and investors, and, if needed, establish separate entities (NewCo) to share risk and revenue.
Kim said, "Recently, global companies are moving not to simply license in but to establish separate companies, co-invest and co-operate, and then acquire when the program advances in clinical stages," adding, "As R&D expense grows, a structure that shares risk and splits returns upon success has become a global trend."
Kim said, "Yuhan's annual R&D investment is about 250 billion won, of which around 150 billion won goes solely to developing global innovative new drugs," adding, "It is realistically burdensome to advance all current pipelines through late-stage and phase 3 development solely with our own expense."
To that end, Yuhan said it is strengthening its global business development (BD) organization centered on its U.S. subsidiary, Yuhan USA. Kim said, "In the past, NewCo creation was led by overseas venture capital or global funds, but recently domestic capital has been participating actively as well."
Kim also mentioned the cases of the U.S. biotech company Regeneron and Beigene, now called BioNMedison, a Nasdaq-listed company registered in Switzerland. Both corporations secured in-house pipelines (drug candidates) necessary 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 simultaneously secure in-house pipelines needed for combination strategies," adding, "Among domestic companies, I believe only Yuhan has such a lineup."
How the organization is run is also changing. Yuhan recently established a Scientific Advisory Board (SAB) composed of external experts. It has appointed 14 advisors so far and is disclosing them on its website.
Kim said, "The aim is to pool experts' views to drive successful development and even reflect feedback from clinical settings where the drugs will actually be used," adding, "We are setting R&D investment priorities based on systematic progress management and evaluation."
He added, "In the past, considering researchers' effort and dedication, there were times we hesitated to discontinue projects that lacked competitiveness," explaining, "Now we have a system that enables bolder and more objective decision-making based on external expert evaluations."
Research direction has also shifted. Previously, development focused on "best-in-class" drugs that improved efficacy or safety over competitors; going forward, it is moving toward "first-in-class" new drugs with novel mechanisms of action and platform technology-centered approaches.
◇ "Targeting even those once untreatable"… strengthening TPD and AI strategies
In particular, Yuhan presented targeted protein degradation (TPD) as a next-generation core pillar. Unlike existing drugs that merely inhibit the function of disease-causing proteins, TPD is a next-generation technology that degrades and removes the proteins themselves inside cells. Because it can reach proteins that were difficult to tackle with conventional drugs, it is drawing attention in the global pharmaceutical industry as a next-generation platform technology.
Yuhan has formed a dedicated TPD team and said the first project has been proposed and is preparing to start development. It is especially focusing on next-generation approaches that overcome the limits of the existing 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 hinders absorption in the body, makes oral (pill) development difficult, and limits delivery to specific tissues such as the brain."
He continued, "More recently, 'molecular glue degraders' that remove target proteins by connecting disease proteins and the intracellular degradation system using small molecules are attracting attention as a 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."
It is also building the AI-based new drug development platform Yu-NIVUS. The key is automating the design-make-test-analyze (DMTA) cycle by using AI to connect candidate design, synthesis, activity prediction, and optimization. Director 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."
Driving these simultaneous organizational and strategic changes at Yuhan is the question of what comes after the lung cancer treatment Leclaza, which succeeded in development and commercialization. Based on global commercialization experience, it aims to grow into a global pharmaceutical corporations that continuously produce new drugs. Kim said, "We are not aiming for small markets like second-line or third-line," emphasizing, "We will create a global blockbuster that can move up into the first-line standard-of-care market."