Siglec Programs
Leveraging Siglec antibodies to outsmart cancer
What are Siglecs?
We are developing a Siglec agonist fusion protein and an antagonist anti-Siglec antibody to reduce immune-related adverse events (irAEs) and fight solid tumors.
1. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Chen GY, Tang J, Zheng P, Liu Y. Science. 2009 Mar 27;323(5922):1722-5. doi: 10.1126/science.1168988.
AI-071: a next-generation agonistic Siglec ligand
Immunotherapies can come with many irAEs. We’ve developed an agonistic Siglec antibody to help mitigate the excessive adverse events that comes with cancer treatments.
Our Siglec agonist, AI-071, is designed for broad siglec coverage, with potential application across immunotherapy-treated indications. Our unique Siglec agonist offers:
Broader Siglec coverage
Potentially stronger biologic activity
Improved processibility and productivity
In preclinical mouse models, treatment with AI-071 significantly reduced mortality of animals receiving anti-CTLA-4 and anti-PD-1 combination therapy and extended survival from irAEs.
AI-071 works to reduce inflammation and irAE in 2 ways:
- AI-071 may bind to Damage Associated Molecular Pattern (DAMP) molecules or Pathogen Associated Molecular Pattern (PAMP) molecules to prevent them from binding to key receptors known to initiate inflammatory responses.
- AI-071 can bind to Siglec signaling components to help reduce inflammatory signaling.
Less inflammatory signaling leads to less inflammation, and potentially less immune-related adverse events for patients.
ONC-841: an anti-Siglec mAb for solid tumors
Siglec-10 is a protein that can potentially suppress the immune system’s ability to fight off diseases.
Some cancers exploit Siglec-10 signaling to avoid being recognized and attacked by the immune system. Targeting this protein in solid tumors may enable the patient’s immune system to better fight cancer.2 Our potential first-in-class anti-Siglec10 mAb has shown antitumor activity in syngeneic xenograft models.
See how we turn our science into action.
2. Barkal AA, Brewer RE, Markovic M, Kowarsky M, Barkal SA, Zaro BW, Krishnan V, Hatakeyama J, Dorigo O, Barkal LJ, Weissman IL. CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. 2019 Aug;572(7769):392-396. doi: 10.1038/s41586-019-1456-0.