Kairos Pharma and Bayer will evaluate ENV-105 in combination with Xofigo in metastatic castration-resistant prostate cancer involving bone.

Kairos Pharma has announced a strategic collaboration with Bayer to evaluate its lead antibody ENV-105 in combination with Xofigo (radium-223 dichloride) in patients with metastatic castration-resistant prostate cancer (mCRPC) involving bone.

The collaboration will investigate whether combining ENV-105, also known as carotuximab, with Bayer’s alpha-emitting radiopharmaceutical can help address treatment resistance in advanced prostate cancer.

Kairos Pharma is developing ENV-105 as a CD105/BMP signalling inhibitor and is currently evaluating the antibody in a Phase 1 trial in EGFR-driven non-small cell lung cancer and a Phase 2 trial in castration-resistant prostate cancer.

The company said interim data from its Phase 2 prostate cancer trial showed a median progression-free survival of more than 13 months. The data were presented at the 2025 ESMO Congress in Berlin.

John Yu, CEO, Kairos Pharma, said: “Drug resistance remains one of the greatest challenges in advanced prostate cancer, and XOFIGO, like many standard-of-care therapies, can lose efficacy over time.”

He added: “ENV-105 has already demonstrated the ability to re-sensitize tumors to existing treatments with a strong safety profile, and this collaboration with Bayer represents a major milestone in our mission to deliver more durable and more effective treatment regimens for patients with metastatic prostate cancer.”

Xofigo is an FDA-approved alpha-emitting radiopharmaceutical used to treat mCRPC with symptomatic bone metastases. The treatment is designed to target areas of increased bone turnover associated with prostate cancer metastases.

The collaboration is based on previous preclinical work investigating the potential role of ENV-105 in radiation sensitisation in prostate cancer models.

According to Kairos Pharma, CD105 is upregulated in response to androgen receptor inhibition and ionising radiation. The company said this can activate pro-survival BMP-SMAD signalling pathways that contribute to treatment resistance.

By targeting CD105 with ENV-105, the company is investigating whether resistant tumours can be re-sensitised to treatment and whether the duration and depth of response to Xofigo’s targeted alpha therapy could be extended.

The combination approach comes as researchers continue to investigate strategies to overcome treatment resistance in patients with advanced prostate cancer, where the effectiveness of therapies can decline as the disease progresses.

Neil Bhowmick, chief scientific officer and principal investigator, said: “CD105’s role as a central resistance mechanism validated now across multiple drug classes makes this collaboration scientifically compelling and clinically timely, given XOFIGO’s recent Phase 3 momentum.”

Xofigo is also being evaluated in combination with other treatments, including in the Phase 3 PEACE-3 trial, which the company said demonstrated a 24% reduction in mortality risk when combined with enzalutamide.

Kairos Pharma said its wider development programme for ENV-105 is focused on overcoming mechanisms of cancer drug resistance, with the antibody being investigated across prostate cancer and EGFR-driven non-small cell lung cancer.

The Bayer collaboration will now focus on evaluating the potential of the ENV-105 and Xofigo combination in mCRPC involving bone, adding another approach to the ongoing development of treatment strategies for advanced prostate cancer.