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Another Pharmaceutical Giant Enters the Field of CD47
On September 8, 2020, Pfizer made a US$25 million equity investment in Trillium Therapeutics. However, Pfizer’s investment has nothing to do with any partners or pre-emptive rights acquired by Trillium Therapeutics, and these options remain open. So, what assets are attracting Pfizer?
CD47 is a glycoprotein widely expressed on the surface of a variety of cells. It releases a “don’t eat me” signal by connecting with SIRPα on phagocytes’ surface to prevent macrophages from engulfing healthy cells. However, cancer cells cunningly use this mechanism to induce immunosuppression and escape the phagocytosis of macrophages. In recent years, CD47 has gradually become a star target in immuno-oncology, and investment in this field has also shown substantial growth.
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Trillium Therapeutics is a Canada-based immuno-oncology company dedicated to developing innovative immunotherapies to treat cancer. The company’s clinical projects TTI-621 and TTI-622 are two unique SIRPαFc decoy receptors that can target CD47 and block its activity.
TTI-622 is a SIRPa-IgG4-Fc fusion protein, similar to I-Mab’s candidate drug, it has very weak binding to normal red blood cells and does not cause hemagglutination. Current data show that in patients with relapsed/refractory DLBCL who have previously received multiple therapies, TTI-622 has achieved “comparable” results in a joint study with the highest dose of competing products. Simultaneously, the research results also show that “not all IgG4 are equal”, because Xinji terminated its phase I study of its IgG4-CD47 molecule CC-90002 two years ago. The data of TTI-622 is better than analysts expected. However, using solid single-drug data as a basis makes managers more confident that their drugs will perform better in the combination.
TTI-621 is a SIRPa-IgG1-Fc fusion protein characterized by a very low dose to achieve significant results. Now, the 1.4 mg/kg dose has been considered to be well tolerated in patients with advanced relapsed/refractory hematological cancers.
Trillium Therapeutics plans to continue to evaluate these two projects. Ultimately, the company plans to enter the solid tumor field, and its CEO Jan Skvarka said that Pfizer is very interested in this field.
With the revival of interest in CD47 in the pharmaceutical industry, innovative therapies for the CD47-SIRPα pathway are expected to become another fertile new world in tumor immunity.
Partner Article, By James Hou, Ph.D.
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