B7-H7/HHLA2

EXCITING NEW TARGET

Immunotherapies targeting the B7 receptor family such as PD-1, PD-L1, and CTLA-4 have improved outcomes for many patients and have revolutionized oncology treatment over the past two decades. B7-H7, also know as HHLA2, is a B7 family member whose inhibitory receptor, KIR3DL3, has been recently identified by our co-founders.

B7-H7 is expressed independently of PD-L1 and acts through 1) a unique inhibitory receptor, KIR3DL3 to block T/NK cell activation and 2) a unique stimulatory receptor, TMIGD2, to increase T and NK cell activation.
The upregulation of B7-H7 expression in tumor tissues makes it an ideal tumor-targeting antigen for many different therapeutic payloads in oncology.
The selective expression of B7-H7 in tumor cells enables a biomarker strategy to select patients most likely to benefit from these targeted therapeutic approaches.

A Novel Immuno-Oncology Checkpoint

Immune escape is important for tumor survival. Mechanisms of tumor immune escape can be targeted with therapeutic agents. The B7-H7 immune signaling pathway that NextPoint targets shares similarities with the PD-L1 pathway but is independently expressed and regulated.

B7-H7 inhibits activation of T and NK cells via KIR3DL3. Tumors expressing B7-H7 suppress T and NK cells within the tumor. Therefore, blocking B7-H7-KIR3DL3 interaction to enhance the anti-tumor immune response is an attractive strategy for cancer treatment. B7-H7 has also been shown to bind an activating receptor TMIGD2. To explore the full potential of this axis inhibition, NextPoint Therapeutics is pursuing both B7-H7 and KIR3DL3 specific antibodies, is generating multiple approaches to enable tumor targeting and is approaching modulation of TMIGD2-mediated activity.

A New Tumor-Associated Antigen for Tumor-Targeting Therapies

Strong overexpression of B7-H7 in tumor tissues with limited expression in normal tissues makes it an attractive target for tumor targeting approaches, which can be directed to the tumor via antibody-based binding to B7-H7. These include: targeted chemotherapies (antibody-drug conjugates), targeted radiotherapies, and T cell engagers.

A Potential Biomarker to Identify Patients Most Likely to Respond

High expression of B7-H7 on tumor cells and limited expression it normal tissues makes in an important potential biomarker for selection of patients most likely to respond to therapeutics targeting the B7-H7 checkpoint axis or directly targeting B7-H7.
We are developing an immunohistochemistry assay for detection of B7-H7 that will be used to select participants in clinical studies in addition to exploring integrated biomarker strategies to define optimal patient populations for different treatment approaches.

NPX267

Designed to reverse T and NK cell Suppression

Our co-founders independently identified KIR3DL3 as the inhibitory receptor for B7-H7.

 

KIR3DL3 binding to B7-H7 interferes with the anti-tumor potential of T and NK cells and can contribute to tumor immune escape.

 

KIR3DL3 is unregulated on a subset of antigen-experienced, exhausted effector memory T cells, called TEMRA cells, and on a subpopulation of NK cells.

 

NPX267 is being studied in a phase 1 clinical trial in solid tumor malignancies known to express B7-H7.

NPX887

Designed to block immunosuppression by KIR3DL3 while sparing immunostimulation by TMIGD2

NPX887 targets B7-H7 to block its interaction with KIR3DL3 and to prevent immunosuppression of T and NK cells.

 

NPX887 enables the interaction of B7-H7 with its other ligand, TMIGD2, which can stimulate T and NK cell activation.

 

NPX887 has enhanced Fc receptor function to potentiate ADCC- mediated destruction of B7-H7-positive tumor cells.

 

NPX887 is being studied in patients with solid tumor malignancies known to express B7-H7 in a phase 1 clinical trial.

NPX372

Designed to……CONTENT GOES HERE……CONTENT GOES HERE

Strong overexpression of B7-H7 in tumor tissues with limited expression in normal tissues makes it an attractive target for tumor targeting via T cell engager.

 

NPX372 is an IgG-like T cell engager with two B7-H7 binding domains, a single CD3 binding domain, and an inactivated Fc. Both B7-H7 and CD3 binding domains are cross-reactive to NHP and human targets.

 

NPX372 mediates potent in vitro tumor cytotoxicity with B7-H7 expression level dependency. NPX372 demonstrates efficacy across several in vivo models with complete tumor regressions.

 

NPX 372 can be safely administered preclinically up to mg/kg dose levels. IND submission is planned for 2025.

NPX372

NextPoint is developing NPX372, a novel T-cell engager designed to target B7-H7 in solid tumors, further expanding NextPoint’s multi-modal focus on the emerging B7-H7 axis in cancer therapy.

B7-H7-ADC:

NextPoint is developing a novel antibody-drug conjugate optimized to target B7-H7 on tumor cells.

B7-H7-CD3:

NextPoint is developing a novel and potent T cell engager targeting B7-H7 which is designed to activate a tumor-directed immune response.

Clinical-Stage Project:
NPX267

NPX267 is a first-in-class monoclonal antibody targeting KIR3DL3 which blocks the interaction with B7-H7 to re-activate T and NK cells. NPX267 is being studied in patients with solid tumor malignancies in a Phase 1 clinical trial.

Clinical-Stage Project:
NPX887

NPX887 is an Fc-enhanced monoclonal IgG1 antibody that targets B7-H7 to block its immunosuppressive interaction with KIR3DL3 on T and NK cells while sparing the interaction with its stimulatory ligand, TMIGD2. NPX887 is being studied in patients with solid tumor malignancies in a phase 1 clinical trial.