Pipeline
Pipeline
Sustainable Pipeline of Innovative Immunotherapies
We are developing next-generation immunotherapies that leverage our single-cell technologies and provide unique insights into immunomodulation.
Our sustainable pipeline of immunomodulatory antibodies targets multiple cell types and key immunosuppressive or inflammatory mechanisms for the treatment of cancer and autoimmune disease.
We are currently enrolling cancer patients from DIS® selected indications into three clinical studies. The first study is evaluating HFB200301, a first in class TNFR2 agonist monoclonal antibody (NCT05238883). The second study is evaluating our next generation fully human OX40 agonist monoclonal antibody HFB301001 (NCT05229601). And our third clinical program, HFB200603, a novel BTLA antagonist has just cleared IND and is beginning recruitment.
Our Pipeline
Solid Tumors
Stage
Mechanism of Action
Overview
Immuno-oncology
Target
TNFR2 is a TNF receptor family member expressed on effector and regulatory T cells., In tumors, TNFR2 is expressed more broadly on activated and exhausted T cells than other T cell costimulatory receptors. Therefore, targeting TNFR2 is anticipated to yield greater anti-tumor immunity by stimulating T-cell activation and proliferation in the tumor microenvironment than targeting other costimulatory receptors.
Antibody
Our First-in-Class agonistic anti-TNFR2 candidate antibody, HFB200301, binds potently and selectively to TNFR2, recognizes cyno TNFR2, and induces CD4 and CD8 T cell activation and proliferation cooperatively with TNFα without requiring crosslinking. In vivo, HFB200301 demonstrates potent antitumor activity alone and combined with anti-PD-1 and is well tolerated in mouse and Non-Human Primates.
Clinical Trial Information
The ongoing first-in-human dose escalation study enrolls patients with DIS® selected advanced cancers. Once a recommended dose for expansion is achieved, the study will expand into cohorts for specific cancer types. Identification of biomarkers predictive of response is also being performed. For more information, visit www.clinicaltrials.gov (NCT05238883).
Stage
Mechanism of Action
Overview
Immuno-oncology
Target
OX-40 (CD134, TNFRSF4) is a tumor necrosis factor (TNF) receptor expressed primarily on activated CD4+ and CD8+ T cells and transmits a potent costimulatory signal when engaged. Targeting OX40 with an agonistic antibody has been demonstrated to increase the activity of T cells leading to anti-tumor responses. Several agonistic antibodies against OX40 have been evaluated in the clinical trials with good tolerability. However, so far, limited clinical activities have been observed in the reported clinical trials.
Antibody
HFB301001 is a novel fully human IgG1 class OX-40 agonistic antibody with an optimized pharmacological profile. In contrast to other anti-OX-40 antibodies, the agonistic activity of HFB301001 is further enhanced in the presence of the endogenous ligand OX-40L and does not result in reduced expression of OX-40 on T cells. HFB301001 demonstrated superior anti-tumor activity in a human OX-40 knock-in mouse model compared to a competitor antibody and is positioned as a best-in-class differentiated molecule for enhanced clinical activity.
Clinical Trial Information
The first-in-human dose escalation study will enroll patients with DIS® selected advanced cancers. Once a recommended dose for expansion is achieved, the study will expand into cohorts for specific cancer types. For more information, visit www.clinicaltrials.gov (NCT05229601)
Stage
Mechanism of Action
Overview
Immuno-oncology and Autoimmune Disease
Target
BTLA is an inhibitory immune checkpoint expressed on B and T cells. Interaction of BTLA with its ligand, HVEM, provides an inhibitory signal to immune cells. Therefore, agonizing BTLA has the potential to dampen the immune system in auto-immune diseases, while blocking the BTLA interaction with HVEM could restore anti-tumor immunity in oncology.
Antibody
HFB200603 was identified as a single-digit nanomolar binder to human and cynomolgus BTLA, capable of reversing HVEM-mediated immune suppression in a BTLA-HVEM reporter system and in a primary CD4+ T cell proliferation assay. HFB200603 shows synergistic effect with anti-PD-1 to enhance IFN-γ production and demonstrates favorable developability and pharmacokinetic profiles.
Mining the antibody repertoire of plasma cells and plasmablasts could enable the discovery of useful antibodies for therapeutic or research purposes…Read more
We are excited to share with the oncology research community at AACR updates for two of our preclinical development programs – HFB200603, a novel anti-BTLA blocking antibody on track for IND submission, and HFB101110, an anti-CCR8 depleting antibody that was recently licensed to FibroGen…Read more
Presenters: Juying Li, Qian Zhang, Bingqing Shen, Manan Shah, Mingjie Chen, Sharon Li, Ling Dong, Francisco Adrian, Liang Schweizer…Read more
Stage
Mechanism of Action
Overview
Immuno-oncology
Target
Galactoside-binding lectin Galectin 9 (Gal-9) is a key pleiotropic immunosuppressive modulator present in the tumor microenvironment. High Gal-9 expression has been reported in different types of cancers including hematological malignancies and multiple solid tumors. Neutralization of Gal-9 has the potential to enhance anti-tumor immune responses in the tumor micro-environment.
Antibody
Our anti-Gal-9 blocking antibody, HFB200901, has demonstrated single agent anti-tumor activity in a mouse cancer model, offers improved survival in combination with anti-PD-1 therapy as compared to anti-PD-1 alone, and shows good tolerability in NHPs.
Stage
Mechanism of Action
Overview
Immuno-oncology
Target
CCR8 is a GPCR with prevalent and highly specific expression on immunosuppressive tumor infiltrating regulatory T cells (Tregs) across different tumor types. Stimulation of CCR8 by its ligand results in proliferation of Tregs in the tumor microenvironment and immune-suppression. Targeting CCR8 with an antibody able to mediate cell killing through antibody-dependent cellular cytotoxicity (ADCC) offers the potential to selectively deplete highly immunosuppressive Tregs in the tumor microenvironment and promote anti-tumor immunity.
Antibody
HFB101110, a humanized monoclonal antibody against CCR8 with potent and specific antibody-dependent cellular cytotoxicity (ADCC) activity. HFB101110 specifically recognizes an epitope on the N-terminus extracellular domain of CCR8 and does not recognize the closely related chemokine receptor CCR4. HFB101110 acts through a dual mechanism of action, by both depleting CCR8+ cells via ADCC and blocking binding of the CCL1 chemokine to its receptor CCR8.
Mining the antibody repertoire of plasma cells and plasmablasts could enable the discovery of useful antibodies for therapeutic or research purposes…Read more
We are excited to share with the oncology research community at AACR updates for two of our preclinical development programs – HFB200603, a novel anti-BTLA blocking antibody on track for IND submission, and HFB101110, an anti-CCR8 depleting antibody that was recently licensed to FibroGen…Read more
Presenters: Roshan Kumar, Julie Prigent, Hombline Poullain, Ayrin Kök, Carine George, Sami Ellouze, Yun-Yueh Lu, Rebecca Silver, Clarisse Monchecourt, Ross Fulton, Qian Zhang, Nicola Beltraminelli, Bernhard Moser, Francisco Adrian, Liang Schweizer…Read more
Stage
Mechanism of Action
Overview
Autoimmune diseases and hematological malignancies
Target
CXCR5 is a GPCR expressed on B cells, as well as on follicular helper T cells. CXCR5 plays a key role in the migration of B cells to germinal centers and the production of autoantibodies. It is implicated in several autoimmune diseases, such as Sjogren’s Syndrome, and in cancers such as B cell lymphomas and several solid cancer types, where it has been associated with metastasis and poor prognosis.
Antibody
HFB100204 is a humanized afucosylated IgG1 (ADCC enhanced) that selectively depletes CXCR5+ B and T follicular helper cells via ADCC, and potentially inhibits their migration
Mining the antibody repertoire of plasma cells and plasmablasts could enable the discovery of useful antibodies for therapeutic or research purposes…Read more
Stage
Mechanism of Action
Overview
Immuno-oncology and Autoimmune Disease
Target
BTLA is an inhibitory immune checkpoint expressed on B and T cells. Interaction of BTLA with its ligand, HVEM, provides an inhibitory signal to immune cells. While blocking the BTLA interaction with HVEM could re-stimulate anti-tumor immunity in oncology, BTLA agonism has the potential to dampen the immune system in auto-immune diseases.
Antibody
HFB200604 was identified as a single-digit nanomolar binder to human and cynomolgus BTLA, capable of inhibiting the proliferation of primary human B cell and activation of T cells. HFB200604 exhibits favorable mouse PK and developability profiles and controls disease in a humanized mouse model of GvHD. We foresee applications for HFB200604 in multiple immune-mediated diseases.
Mining the antibody repertoire of plasma cells and plasmablasts could enable the discovery of useful antibodies for therapeutic or research purposes…Read more
Featured Licensed Partners
Affiliated Programs
Discovery of Novel Targets Leading to a New Generation of Precision Immunotherapies
Target selection based on key immunomodulatory pathways underlying immuno-suppression and inflammation in multiple immune cell types
Our target discovery approaches:
- Target identification from proprietary single cell patient datasets, focused on mechanisms of resistance to current therapies
- Multi-targeting strategy with novel multi-specific formats
- Collaborations with top immunology/immuno-oncology experts in the world
