CD47 blockade continues on its bumpy journey

Though CD47 blockade features over 30 different clinical-stage assets, according to Evaluate Pharma, little seems to go smoothly. Yesterday I-Mab was forced to defend Abbvie’s decision to terminate a multiple myeloma trial of lemzoparlimab, the groups’ joint anti-CD47 MAb whose listing was recently marked “terminated (strategic considerations)”. In an investor statement I-Mab said there was no safety concern behind this “exploratory trial” being halted, adding that development in acute myelogenous leukaemia (AML) and myelodysplastic syndromes (MDS) was continuing. While Abbvie’s decision might be benign, it coincides with ALX Oncology last month pausing the Aspen-05 trial of evorpacept in AML while it awaits dose-optimisation data from the Aspen-02 MDS study; the project had disappointed clinically last year. In January some trials of magrolimab, which Gilead had acquired with its $4.9bn purchase of Forty Seven, were halted over suspected adverse events; the hold was lifted in April on AML and MDS trials, and in June on those in multiple myeloma and lymphoma. Some of the most keenly watched anti-CD47 projects are TTI-621 and TTI-622, which Pfizer had acquired with Trillium for $2.3bn a year ago. I-Mab is due to present a lemzoparlimab update in high-risk MDS at Esmo in September.

Selected clinical projects targeting the CD47/SIRPα axis
Project Company Mechanism Lead indication
Phase 3
Magrolimab Gilead Sciences (ex Forty Seven) Anti-CD47 MAb Enhance trial in MDS
Enhance-3 trial in AML
Phase 2/3
Evorpacept ALX Oncology Anti-CD47/SIRPα fusion protein  Aspen-06 combo in Her2+ve gastric cancer; ph2 for AML & MDS
Phase 2
AK117 Akeso Biopharma Anti-CD47 MAb AK112 (PD-1/VEGF bispecific) combo in solid tumours
HX009 Waterstone Hanxbio Anti-CD47xPD-1 bispecific MAb Solid tumours
Phase 1/2
Lemzoparlimab I-Mab/Abbvie Anti-CD47 MAb AML & MDS
IBI188 Innovent Biologics Anti-CD47 MAb AML
AO-176 Arch Oncology (Roche backed) Anti-CD47 MAb Multiple myeloma; Keytruda combo in solid tumours
JMT601/CPO107 Conjupro (CSPC Pharmaceutical) Anti-CD47xCD20 bispecific MAb Lymphoma
TTI-621 Pfizer (ex Trillium) Anti-CD47 Fc-fusion protein Leiomyosarcoma; ph1 in haem & solid tumours
DSP107 Kahr Medical Anti-CD47/4-1BB fusion protein Solid tumours
IMM01 Immuneonco Anti-SIRPα fusion protein AML & MDS
Note: only projects above phase 1 are listed. Source: Evaluate Pharma &

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