F-star is developing novel, innovative tetravalent bispecific antibodies intended to transform the lives of individuals with hard-to-treat cancers.
Why tetravalency? In our quest to overcome many of the challenges facing current immuno-oncology therapies, we discovered that a 2 + 2 approach, with four binding sites, would drive strong dual immune activation capabilities.
- Natural human antibody format means easier manufacturing with a favorable clinical safety profile
- Four binding sites enhances targeted bispecific activity
- Receptor clustering drives stronger biological potency than other bispecific approaches
Technology Platform
Our Bispecific Antibody Platform
F-star’s proprietary technology enables the creation of two additional distinct antigen binding sites in the Fc region of a natural antibody, termed an Fcab. The resulting tetravalent (2+2) mAb2 bispecifics bind simultaneously to two different antigens and are being designed to deliver focused, potent and safe immune activation.
Activating the Immune System with our Tetravalent Bispecifics
Our differentiated tetravalent mAb2 bispecifics are designed to enable safe, potent immune activation by:
- CROSSLINKING. Bringing together two different cells, or two receptors on the same cell, to activate the immune system.
- CLUSTERING. Receptors are brought together on the cell surface to activate key immune cell pathways.
- CONDITIONALITY. Immune cells are only activated when their receptors are simultaneously bound by our bispecifics, which is designed to lead to safe activation.
Our bispecifics are natural full-length human antibodies with substantial advantages for development:
- Manufactured using well established manufacturing processes
- No additional domains that may complicate manufacturing, such as domain assembly or other modifications
Introduction of the Fcab antigen binding sites does not interfere with binding to the Fc receptors. Mutations can be introduced into the Fcγ receptor binding sites to provide optimal immune activation, with a desirable safety profile.
The ability to engineer binding sites into an Fc region also provides the potential to create a number of other technology formats such as trispecifics and Fc-fusion proteins.
Publications
F-star develops novel bispecific antibodies to improve the treatment of serious diseases, with a focus on immuno-oncology.
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FS118
Cancer Trial Highlights Potential for Checkpoint Inhibitors
April 29, 2021A first-in-human study of FS118, a tetravalent bispecific antibody targeting LAG-3 and PD-L1, in patients with advanced cancer and resistance to PD-(L)1 therapy
November 11, 2020FS118, a Bispecific Antibody Targeting LAG-3 and PD-L1, Enhances T-Cell Activation Resulting in Potent Antitumor Activity
April 16, 2020 -
FS120
FS120, an OX40/CD137 tetravalent bispecific dual agonist antibody, synergistically increases the antitumor activity of anti-PD-1 in preclinical studies
November 12, 2021A First-in-Human Phase 1 Study of FS120, an OX40/CD137 tetravalent bispecific antibody, in patients with advanced malignancies
September 16, 2021CD137/OX40 Bispecific Antibody Induces Potent Antitumor Activity that Is Dependent on Target Coengagement
April 9, 2020Crosslink-independent CD137 Agonism is Associated with Liver Inflammation
November 6, 2019 -
FS222
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SB11285
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Technology Publications