YH42946 / J Ints Bio, Yuhan Corp - LARVOL DELTA

A Phase 1/2, First in Human Study of YH42946, a Novel Oral HER2 TKI, in Advanced Solid Tumors With HER2 Aberration and EGFR Exon 20 Insertion (IASLC-WCLC 2026) - P1/2 | "As clinical data mature, additional cohorts may be incorporated in Part 2 to further explore the therapeutic potential of YH42946 in molecularly defined patient populations. ClinicalTrials.gov identifier NCT06616766."

EGFR exon 20 • First-in-human • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • EGFR • HER-2

A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate Safety, Tolerability, PK and Anti-tumor Activity of YH42946 (clinicaltrials.gov) - P1/2 | N=161 | Recruiting | Sponsor: Yuhan Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Antitumor activity of YH42946, a potent tyrosine kinase inhibitor, in NSCLC harboring EGFR exon 20 insertion mutations (AACR 2025) - "It demonstrated superior activity compared to Mobocertinib (IC50 < 30 nM for ASV and IC50 < 30 nM for SVD), Furmonertinib (IC50 < 100 nM for ASV and IC50 < 100 nM for SVD), and Zipalertinib (IC50 < 100 nM for ASV and IC50 < 100 nM for SVD), and was comparable to Poziotinib (IC50 < 10 nM for ASV and IC50 < 10 nM for SVD). YH42946 is a potent small-molecule inhibitor that selectively targets EGFR ex20ins while sparing EGFR WT in preclinical models, offering potential therapeutic benefits for NSCLC patients with EGFR ex20ins mutations. Additionally, YH42946 has demonstrated effective inhibition of the EGFR pathway. Given these robust activities against EGFR ex20ins, YH42946 is anticipated to provide a significant therapeutic option for NSCLC patients harboring EGFR ex20ins mutations."

EGFR exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Yuhan Corporation announces preclinical study results of targeted anticancer drug YH42946 and immunotherapy drug YH32364 at AACR [Google translation] (BioTimes) - "At this conference, Professor Cho Byung-chul’s research team at Yonsei Cancer Hospital presented key preclinical results based on various cell experiments, including patient-derived cells (PDCs), on the anticancer effect of YH42946 on EGFR exon 20 insertion mutations in non-small cell lung cancer. As a result, YH42946 was confirmed to have a broad inhibitory effect on EGFR exon 20 insertion mutations as well as activity against the existing HER2 exon 20 insertion mutation....In vitro cell-based tests showed that YH32364 exhibited potent antitumor effects, including T cell activation, compared to competitive drugs in lung and colon cancer cells expressing EGFR and harboring KRAS mutations, and confirmed combined efficacy with anti-PD1 antibodies in head and neck cancer cells."

Preclinical • Colon Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer

A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate Safety, Tolerability, PK and Anti-tumor Activity of YH42946 (clinicaltrials.gov) - P1/2 | N=161 | Recruiting | Sponsor: Yuhan Corporation

EGFR exon 20 • Metastases • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Yuhan to start phase 1/2 trial of oral lung cancer drug in Korea (Korea Biomedical Review) - "According to a Thursday update from the Ministry of Food and Drug Safety on domestic clinical trials, the regulator approved 'an open-label, multicenter, first-in-human phase 1 and 2 study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of YH42946 in patients with locally advanced or metastatic solid tumors with human epidermal growth factor receptor 2 (HER2) abnormalities and epidermal growth factor receptor (EGFR) exon 20 insertions'...In the U.S. in May 2024, YH42946 received approval from the FDA for a phase 1/2 clinical trial....'YH42946 is one of the next targeted anti-cancer drugs in our pipeline following Leclaza, and we plan to start recruiting patients in Korea and the U.S. in the second half of the year.'"

IND • New P1/2 trial • Lung Cancer • Oncology • Solid Tumor

JIN-A04, Highly Effective and Brain-penetrant Tyrosine Kinase Inhibitor Targeting HER2 Exon20 Insertion Mutations in NSCLC (IASLC-WCLC 2023) - "Based on these in vivo studies, JIN-A04 has the potential to be a best-in-class drug candidate to address this unmet clinical need. JIN-A04 exhibited robust activity against HER2GSP mutation and demonstrated intracranial activity with HER2VC model. Therefore, JIN-A04 is expected to provide a therapeutic opportunity for patients with NSCLC who harbor HER2 exon20 insertion mutation."

Brain Cancer • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Yuhan acquires J INTS BIO’s TKI to develop first-in-class NSCLC drug (Korea Biomedical Review) - "Yuhan Corp. said on Tuesday it signed a licensing-in agreement with J INTS BIO for its HER2-targeting tyrosine kinase inhibitor (TKI), JIN-A04, to work on a treatment for non-small cell lung cancer (NSCLC). The total value of the agreement is 429.8 billion won (approximately $324.9 million), including an upfront payment of 2.5 billion won with milestones based on future development, licensing, and sales....J INTS BIO’s JIN-A04 is a first-in-class oral TKI drug candidate that targets the HER2 gene in NSCLC."

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Yuhan Corporation and J INTS BIO inked a licensing agreement for a New Drug Candidate targeting HER2 NSCLC (PRNewswire) - "Yuhan Corporation...announced...that it has signed an in-license agreement with J INTS BIO (CEO, Anna Jo) for a Tyrosine Kinase Inhibitor (TKI) targeting HER2, 'JIN-A04'. The total contract size is 325 million dollars, and it includes an upfront payment of 1.9 million dollars and milestone payments according to future development, permits, and sales."

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

J INTS BIO, AACR 2023 - Presentation of preclinical study results of 'JIN-A04', an oral target therapy for HER2 exon insertion mutation NSCLC (PRNewswire) - "J INTS BIO announced the poster presentation of its novel, orally administered TKI 'JIN-A04' targeting NSCLC with HER2 exon 20 insertion mutation at the annual meeting of the American Association of Cancer Research 2023....The data presented showed that 'JIN-A04' has potent efficacy against HER2 Exon20 insertion mutant NSCLC cell lines while showing no activity in normal cell lines in an in-vitro study, and in-vivo mouse models using HER2 Exon20 insertion mutation cell lines showed strong inhibitory activity with significant tumor regression."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • HER-2

JIN-A04, highly effective tyrosine kinase inhibitor targeting HER2 exon 20 insertion mutations in NSCLC (AACR 2023) - "It was superior to Mobocertinib (IC50 = 27.1 nM for YVMA and IC50 = 3.3 nM for GSP) and comparable with Poziotinib (IC50 = 3.4 nM for YVMA and IC50 = 0.4 nM for GSP). JIN-A04 is highly potent against HER2 exon 20 insertion mutations including YVMA and GSP, while largely sparing HER2 WT activity. Also, JIN-A04 demonstrated effective HER2 pathway inhibition. Based on these robust activities for HER2 exon 20 insertion, JIN-A04 is expected to provide a potent therapeutic opportunity for NSCLC patients with HER2 exon20 insertion mutations."

HER2 exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

K-Bio, a large number of AACR launches… active search for new drug candidates [Google translation] (Medical Observer) - "Hanmi Pharmaceutical will announce the results of seven studies, the most among domestic companies. Research projects such as 'LAPS IL-2 Analog', which is being developed as an innovative immuno-oncology drug, will be released as posters....JInz Bio will present a poster presentation on the preclinical results of 'JIN-A04', an oral tyrosine kinase (TKI) inhibitor currently under development targeting non-small cell lung cancer HER2 exon 20 insertion mutation. The company said that JIN-A04 showed strong efficacy against HER2 exon 20 insertion mutant cells of non-small cell lung cancer in an in vitro study, and in an in vivo study using HER2 exon 20 insertion mutant cells I explained that it showed my efficacy."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

J INTS BIO, Oral TKI 'JIN-A04', poster presentation of HER2 exon20 insertion mutation in NSCLC (PRNewswire) - "J INTS BIO announced that the preclinical results of 'JIN-A04,' a novel oral tyrosine kinase inhibitor (TKI) targeting HER2 Exon20 insertion mutation in NSCLC, will be presented at the upcoming 2023 American Cancer Research Association meeting in Orlando, U.S. from April 14 to 19....'If JIN-A04 is approved for designation as an orphan drug, it will be possible for it to be used in patients after the completion of Phase 1 and Phase 2 clinical trials.' To this end, the company plans to submit an IND to the US and Korea in the first half of this year, allowing us to enter Phase 1 clinical study in the US and Korea simultaneously."

IND • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Exon 20