THE SCIENCE

Our Approach

NextPoint is launching a new world of precision immuno-oncology and tumor-targeting therapeutics through its leading scientific work on the novel B7-H7/HHLA2 axis. Our innovative approach integrates foundational science with a defined clinical biomarker to identify the right patient population for each B7-H7-directed therapy, so that we can deliver a new class of monotherapies for patients including those who do not benefit from PD-1/L1 inhibitors. Our team of proven drug developers is simultaneously advancing therapeutic approaches blocking the B7-H7 immune signaling pathway and utilizing the unique upregulation of B7-H7 in cancer as an anchor for tumor-targeting treatment modalities.
Learn about our science

EXCITING NEW TARGET

B7-H7/HHLA2 is an 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.

STRATEGY

B7-H7/HHLA2 - 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.

STRATEGY

B7-H7/HHLA2 - A Novel 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.

B7-H7 staining in lung
adenocarcinoma

STRATEGY

B7-H7/HHLA2 - 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 (A KIR3DL3 SPECIFIC ANTIBODY)

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 upregulated 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 (A B7-H7/HHLA2 SPECIFIC ANTIBODY)

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.

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.