BerGenBio presents positive preclinical data on BGB324

Posted: 21 September 2015 | Victoria White

The data highlights that BGB324 used in combination with immune checkpoint inhibitors in mouse carcinoma models showed enhanced tumour clearance compared with checkpoint inhibition alone…

BerGenBio has announced new preclinical data on its lead compound, BGB324, in combination with immune checkpoint inhibitors.

This preclinical data highlights that BGB324, a first-in-class, highly selective small molecule inhibitor of the Axl receptor tyrosine kinase, used in combination with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1) in mouse carcinoma models showed enhanced tumour clearance, survival and tumour infiltration of cytotoxic T lymphocytes compared with checkpoint inhibition alone.

BGB324 is the only selective Axl inhibitor currently in development

The studies were conducted in an aggressive mammary adenocarcinoma (4T1) syngeneic mouse model. BGB324 (50 mg/kg bid) significantly enhanced responsiveness to anti-CTLA-4/anti-PD-1 treatment (10 mg/kg of each, 4 doses) in Balb/C mice bearing established 4T1 tumours. The well-tolerated combination of BGB324 + anti-CTLA-4/anti-PD-1 resulted in durable primary tumour clearance in 23% of treated mice versus 5.6% obtained with anti-CTLA-4/anti-PD-1 alone. In a separate study, BGB324 + anti-CTLA-4 treated resulted in 22% long-term primary tumour clearance while no response was observed with anti-CTLA4 treatment alone. The extensive metastasis to the lung, liver and spleen characteristic of this model were concomitantly abrogated in the animals responding to the combination treatment. In addition, BGB324 + anti-CTLA-4/anti-PD-1 treated tumours displayed enhanced infiltration of cytotoxic T lymphocytes. Importantly, responding animals rejected orthotopic 4T1 tumor cell re-challenge, demonstrating sustained tumour immunity.

BGB324 is the only selective Axl inhibitor currently in clinical development. Phase Ib clinical trials are underway as single agent and in combination with standard of care drug (cytarabine) in acute myeloid leukaemia (AML), and in combination with erlotinib in non-small cell lung cancer (NSCLC).

Richard Godfrey, Chief Executive Officer of BerGenBio, commented, “This promising new preclinical data demonstrates the rationale for combining BGB324 with immune checkpoint inhibitors to treat aggressive cancer. In addition to the ongoing development of BGB324 in AML and NSCLC, this data suggests that BGB324 could also be used in combination with cancer immunotherapeutic agents to enhance their efficiency.”

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