Pfizer hopes Gilead’s CD47 issues aren’t catching

2022 has so far been a year of clinical holds, and yet another has come courtesy of Gilead, which has halted some studies of its anti-CD47 project magrolimab after seeing adverse events. This is another blow to Gilead’s deal strategy – it paid $4.9bn for magrolimab’s developer Forty Seven in 2020 – but the news could also make Pfizer nervous. The pharma giant recently made its own CD47 move, buying Trillium for $2.3bn. Gilead did not give details of the adverse events, but the issue seems to be specific to a combination of magrolimab plus the chemo azacitidine. Evercore ISI’s Umer Raffat speculated that it could be related to cytopenia rather than anaemia; the latter has previously been seen with magrolimab. Notably, Pfizer’s TTI-621 and TI-622 are not being trialled alongside azacitidine, but other CD47 contenders are, including ALX Oncology’s evorpacept and I-Mab/Abbvie’s lemzoparlimab. Even the best-case scenario for Gilead, a delay rather than the end of magrolimab, could see it lose first-mover advantage in a very crowded field. The news also puts more pressure on the imminent readout from the Tropics-02 trial of Trodelvy, gained through Gilead's $21bn purchase of Immunomedics, another deal that could prove too rich.

Anti-CD47s in the clinic
Project Company (originator)
Description
Note
Phase 3
Magrolimab Gilead (Forty Seven) Anti-CD47 MAb On partial clinical hold due to suspected unexpected serious adverse reactions with azacitidine combo
Phase 2/3
ALX148 (evorpacept) ALX Oncology Anti-CD47/SIRPα fusion protein  Recent disappointments in ph1/2 Aspen-02 + azacitidine in MDS & ph1 Aspen-01 in solid tumours; ph2/3 Aspen-06 in gastric ongoing
Phase 2
Lemzoparlimab (TJC4) Abbvie (I-Mab) Anti-CD47 MAb Ph2 China study + toripalimab in solid tumours began Jan 2022; ph1/2 +/- azacitidine in AML/MDS
HX009 Waterstone Hanxbio Anti-CD47xPD-1 bispecific China study in solid tumours
Phase 1/2
TTI-621 Pfizer (Trillium) Anti-CD47/SIRPα fusion protein  Ph1/2 in leiomyosarcoma; ph1 in haem cancers/solid tumours
AO-176 Arch Oncology Anti-CD47 MAb Ph1/2 in solid tumours & multiple myeloma
DSP107 Kahr Medical CD47x4-1BB fusion protein Ph1/2 in solid tumours
IBI188 Innovent Biologics Anti-CD47 MAb Ph1/2 China study + azacitidine in AML
IMM01 Immuneonco Biopharmaceuticals Anti-SIRPα fusion protein  Ph1/2 + azacitidine in AML/MDS
Phase 1
TTI-622 Pfizer (Trillium) Anti-CD47/SIRPα fusion protein  Ph1 in haem cancers
CC-95251 Bristol-Myers Squibb (Celgene)  Anti-SIRPα MAb Ph1 in haem cancers/solid tumours & AML/MDS (+/- azacitidine)
TG-1801 TG Therapeutics ( Light Chain Bioscience) Anti-CD19-CD47 bispecific  Ph1 in B-cell lymphoma & B-cell lymphoma/CLL
IMC-002 Immuneoncia Therapeutics (JV between Sorrento & Yuhan) Anti-CD47 MAb Ph1 in solid tumours/lymphoma
STI-6643 Sorrento Therapeutics Anti-CD47 MAb Ph1 in solid tumours
GS-0189 (FSI-189) Gilead Sciences (Forty Seven) Anti-SIRPα MAb Ph1 in NHL
SL-172154 Shattuck Labs Anti-CD47 & CD40 fusion protein Ph1 in ovarian cancer & H&N cancers
Effi-dem (BI 765063/OSE-172) Boehringer Ingelheim/OSE Immunotherapeutics (Effimune) Anti-SIRPα MAb Ph1 in solid tumours in Europe & Japan 
IBI322 Innovent Biologics Anti-CD47xPD-L1 bispecific Ph1 China studies in solid tumours & haem cancers; US ph1 not yet recruiting
ZL-1201 Zai Lab Anti-CD47 MAb Ph1 in advanced cancers
PF-07257876 Pfizer CD47xPD-L1 bispecific Ph1 in solid tumours
IMM0306 Immuneonco Biopharmaceuticals CD47xCD20 bispecific Ph1 in B-NHL
TQB2928 Chia Tai Tianqing Pharmaceutical Group Anti-CD47/SIRPα Ph1 in advanced cancers
Source: Evaluate Pharma & clinicaltrials.gov.

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