Yuhan disclosed the development progress of next-generation drug candidates to lead the way after the commercialization success of the non-small cell lung cancer (NSCLC) drug Leclaza (ingredient name Lazertinib).
It appears that clinical-stage research and development in the core pipelines for allergy, oncology, and metabolic diseases—capable of global technology transfer—is proceeding smoothly.
On the afternoon of the 28th, at Yuhan headquarters in Dongjak-gu, Seoul, R&D head Kim Yeol-hong said at the investor relations (IR) event R&D Day, Yuhan has five post-Leclaza assets, adding, Deals with high likelihood of actual commercialization (license agreements) tend to occur from late phase 1 to early phase 2, and the key pipelines are now entering that stage.
Negotiations with global pharmaceutical companies appear to be making progress on Yuhan's major pipelines.
The company's candidates presented as core pipelines today are: ▲ the new allergy drug candidate YH35324 ▲ the HER2 bispecific antibody YH32367 ▲ the HER2 targeted anticancer agent (TKI) YH42946 ▲ the EGFR bispecific antibody YH32364 ▲ the MASH (metabolic dysfunction–associated steatohepatitis) new drug candidate YH25724.
YH35324 is an IgE Trap–based drug that tightly binds and blocks IgE, the immune protein that triggers allergic reactions. In the current global market, Novartis' XOLAIR (ingredient name Omalizumab) is representative, and YH35324 is drawing market attention as a candidate expected to surpass it.
Regarding YH35324, Kim said, It shows rapid efficacy and outstanding clinical effectiveness sufficient to expand the treatment range to patients with autoantibodies, adding, Safety is excellent, with virtually no adverse events reported in clinical trials.
He also stressed that it has an advantage compared with the competing candidate EXL111 recently in-licensed by Novartis. A global trial is underway in Europe, China, Korea, and Japan. About 40 people have passed screening, and 14 have been enrolled. Kim said, A deal is quite imminent.
Another area Yuhan presented as a next-generation pillar is HER2 oncology drug candidates. HER2 is a protein involved in cancer cell growth and is overexpressed or mutated in breast, gastric, lung, and biliary tract cancers.
Introducing the HER2 bispecific antibody YH32367 and the HER2 small-molecule targeted anticancer agent (TKI) YH42946 together, Kim said, Ultimately, the goal is to directly create, with Yuhan drugs, a combination like Amivantamab + Leclaza in the HER2 space. As with the strategy of combining Johnson & Johnson (J&J)'s bispecific antibody Amivantamab with Yuhan's lung cancer drug Leclaza, the intention is to combine anticancer agents with different mechanisms to maximize treatment effect.
YH32367 is a bispecific antibody that blocks HER2 while simultaneously stimulating 4-1BB, an immune cell–activating receptor. A phase 1b trial is underway in patients with biliary tract cancer.
Kim said, A very deep response emerged in the dose-escalation stage, adding, Cases of complete response (CR) were also identified. He also explained that in some patients, the duration of response is continuing for a year and a half to more than two years.
The HER2 market is projected to grow from about 17 trillion won in 2022 to 26 trillion won in 2028. Regarding YH42946, a treatment for HER2-mutant non-small cell lung cancer (NSCLC), he described it as a pipeline that closely resembles Leclaza.
YH42946 is a TKI that blocks intracellular HER2 signaling. It has reached the final stage of phase 1 dose escalation. Kim said complete responses (CR) were observed even in patients who failed prior treatments and in those who failed HER2 ADC (antibody-drug conjugate) therapy. He also said partial responses (PR) have been observed in 10 patients so far.
Yuhan is also pursuing a strategy of combining YH42946 with YH32367 and with immuno-oncology agents. Kim emphasized, The goal is not to be a second- or third-line therapy, but ultimately to enter the first-line standard of care.
The EGFR–4-1BB bispecific antibody YH32364 is also a core candidate. EGFR is a key oncogene in lung, colorectal, and head and neck cancers. YH32364 blocks EGFR while simultaneously inducing immune cell activation. It has entered the final stage of phase 1 dose escalation.
Kim said, Patients with long-term disease control without progression and responders are being observed, adding, Discussions with a global pharmaceutical company on the direction of a joint clinical program have been concluded, and we are now drafting the contract. He continued, There will be an opportunity to announce this soon.
The MASH (metabolic dysfunction–associated steatohepatitis) therapy YH25724 was also presented as a key pipeline. This candidate is a fusion protein that combines GLP-1, used in obesity and diabetes treatment, with the FGF21 mechanism involved in improving fatty liver and metabolic function.
Kim said, The MASH market is very large, adding, The global patient population is about 348 million. He explained that the current market size is about 5 trillion won, with an expected compound annual growth rate of 17% to 23%. Recently, in the global pharmaceutical industry, deals for candidates with similar mechanisms were made at 7 trillion won, 5 trillion won, and 3 trillion won.
In clinical trials, YH25724 recorded about a 46% reduction in fatty liver by MRI-PDFF. Kim explained, GLP-1 compensated to a considerable extent for adverse effects typical of the FGF21 class, such as diarrhea and weight gain.
A shift in Yuhan's strategy also stands out. The company plans to pivot toward joint development, joint investment, option deals, and establishing NewCos.
Kim said, The current annual R&D investment is about 250 billion won, of which about 150 billion won goes solely to global innovative drug development, adding, It is realistically burdensome to develop all candidates in-house through late-stage trials. He continued, Through a structure of joint funding and risk sharing, we will reduce the clinical cost burden and create a virtuous cycle by reinvesting that into research and development.
He added, We are not targeting small markets like second-line or third-line, emphasizing, We will definitely move into the first-line standard-of-care market and build a global blockbuster.