| Program | Mechanism of Action | Lead ID | Lead OP | IND Enabling | Clinic | |
|---|---|---|---|---|---|---|
| BPT567 (PD1-IL18) Immuno-oncology |
PD-1 blockade + tumor targeting + IL-18 signaling IL-18 binding protein resistant |
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| close x | ||||||
| Several Undisclosed programs Immuno-oncology |
Multi-functional PD-1 Targeted Agents |
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| close x | ||||||
| Numerous undisclosed discovery assets in Oncology and other Disease Areas |
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| close x | ||||||
| Drug | Phase | BPT567 (PD1-IL18) Immuno-oncology | Clinic |
|---|---|
| Several Undisclosed programs Immuno-oncology | Lead OP |
| Numerous undisclosed discovery assets in Oncology and other Disease Areas | Lead ID |
BPT567
(PD1-IL18)
BPT567 is a human anti-programmed cell death protein 1 (PD-1) antibody site-specifically conjugated to an interleukin-18 (IL-18) protein variant payload with decreased binding affinity to the IL-18 binding protein (IL-18BP). Interleukin-18 (IL-18) is a pro-inflammatory cytokine able to trigger both innate and adaptive immune responses and is a potent inducer of interferon gamma (IFN-γ) secretion, making it an attractive candidate for cancer immunotherapy. IL-18BP is a secreted physiologic antagonist that binds IL-18 with high affinity and is induced by IFN-γ in a natural negative feedback loop that neutralizes IL-18 activity. The IL-18 protein payload of BPT567 has been engineered to resist neutralization by IL-18BP, therefore maintaining the desired immunostimulatory activity of IL-18 in the presence of IFN-γ -induced IL-18BP.
BPT567 has been designed to engage both PD‑1 and the IL-18 receptor (IL-18R) in tandem and to preferentially activate immune cells expressing both targets. Simultaneous binding to both receptors results in enhanced IL-18 potency due to cis-signaling i.e., the engagement of PD-1, and blockade of PD-1/PD-L1 interaction, with concurrent IL-18 signaling through the IL-18R on the same cell. In transgenic mice engineered to express human PD-1, BPT567 induces significantly stronger anti-tumor efficacy relative to an anti-PD-1 antibody alone, a non-targeted IL-18 immunoconjugate alone or the combination of the two agents. BPT567 has demonstrated anti-tumor activity in both immune checkpoint inhibitor (ICI)-sensitive and ICI-resistant non-clinical tumor models. As a result of its high anti-tumor potency and relative tumor selectivity demonstrated in non-clinical tumor models, BPT567 is designed to induce lower systemic IL-18R-mediated activation side effects compared to non-targeted IL-18 agents when administered at efficacious doses.
BPT567 is currently investigated in a first-in-human phase 1/2a study in patients with locally advanced or metastatic solid tumors.
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