IDEAYA Biosciences' SHR-4849: A Promising ADC for SCLC and NET Solid Tumors

IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company, has entered into an exclusive license agreement with Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma, SHA: 600276) for SHR-4849, a novel Phase 1 DLL3-targeting Topo-I-payload antibody drug conjugate (ADC) targeting Small Cell Lung Cancer (SCLC) and Neuroendocrine Tumors (NETs). This news has been well-received by investors, with IDEAYA stock (ticker: IDYA) up 3.2% in Monday morning trading. As of the close of trading on Friday, shares of IDEAYA had climbed 15.7% so far this year.

SHR-4849 is a promising ADC that targets DLL3, a protein highly expressed in SCLC and NETs. The drug has shown promising antitumor activity in preclinical studies, including tumor regression as a monotherapy in multiple models. In a Phase 1 clinical trial for advanced solid tumors in China (NCT06443489), SHR-4849 has reached therapeutic dose levels where multiple partial responses have been observed. Among 11 evaluable SCLC subjects treated at therapeutic dose levels, 8 partial responses by RECIST 1.1 were observed, resulting in an overall response rate of ~73% (including both confirmed and unconfirmed responses, all unconfirmed responses were pending further evaluation). As of the data cut-off date, treatment related adverse events (TRAEs) were predominantly Grade 1 or 2, and the Phase 1 dose escalation is ongoing with no reported drug-related discontinuations, and the maximum tolerated dose has not yet been reached.

IDEAYA Biosciences has identified potential synergies and combination opportunities with its DNA Damage Repair (DDR) clinical pipeline, particularly with the Phase 1 PARG inhibitor IDE161. The combination of SHR-4849 and IDE161 has shown enhanced preclinical combination efficacy compared to evaluated topo-payload ADCs alone. This rational clinical combination targets different pathways involved in cancer cell growth and survival, potentially leading to enhanced antitumor activity and improved patient outcomes.

“The Priority Review likely emphasizes FDA’s high interest in approving the drug,” RBC Capital Markets analyst Brian Abrahams wrote in a note. He rates IDEAYA stock at Outperform with a $120 price target. SCLC and NETs are aggressive and often fatal cancers, with limited treatment options available. The approval of SHR-4849 could provide a much-needed new treatment option for patients with these cancers.



While the Phase 1 trial of SHR-4849 is still ongoing, the promising interim data and the potential for rational clinical combinations with IDEAYA's DDR pipeline have investors optimistic about the drug's prospects. The ongoing Phase 1 dose escalation trial is expected to continue, with a US IND filing for SHR-4849 targeted for the first half of 2025.

In a note on Monday, SVB Securities analyst Joseph P. Schwartz said that this setup could improve SHR-4849’s chances, as the FDA now generally prefers to see a confirmatory trial underway at the time of accelerated approval. “Although there was some debate concerning the company’s pursuit of the accelerated pathway, we believe the FDA acceptance of the BLA filing, feedback from doctors in the space, and IDEAYA’s extensive know-how in the ADC space will help to support approval,” Cantor Fitzgerald analyst Kristen Kluska wrote in a note. She rates IDEAYA stock at Overweight with a $110 price target.

In conclusion, IDEAYA Biosciences' SHR-4849 is a promising ADC for SCLC and NET solid tumors, with a manageable safety profile and potential for rational clinical combinations with the company's DDR pipeline. The ongoing Phase 1 trial and the potential for accelerated approval make this an exciting investment opportunity in the precision medicine oncology space.