Against the odds biopharma throws all it can at CD47
It’s extraordinary that CD47 blockade features in 43 active clinical projects across 145 clinical studies, as revealed by OncologyPipeline. In addition there are 38 preclinical assets, and work is spread among naked antibodies, fusion proteins, bispecifics and even a Car-T therapy. Against such enthusiasm stands the uncomfortable fact that this mechanism’s leading exponents have not done well, and just last week AbbVie finally pulled the plug on a $200m 2020 tie-up with I-Mab covering the anti-CD47 MAb lemzoparlimab. That brought to an end an agonising year for I-Mab, during which AbbVie scrapped first one then the second lemzoparlimab study, all the while insisting that the deal was alive and well. Also prominent is magrolimab, which Gilead had acquired in the $4.9bn buyout of Forty Seven, but which has suffered several trial discontinuations and clinical holds. ALX Oncology’s evorpacept had once stood as an unpartnered asset that had been hotly tipped by the sellside, but it has had its own share of clinical setbacks; ALX’s stock price has halved over the past 12 months. In 2021 Pfizer paid $2.3bn for Trillium, and last December touted the latter’s anti-CD47 fusion protein maplirpacept as a potential $3bn-a-year seller.
Selected industry projects targeting CD47
| Project | Company | Note |
|---|---|---|
| Magrolimab | Gilead Sciences (ex Forty Seven) | Enhance-3 study put on partial US clinicalk hold in Aug 2023; Enhance trial discontinued for futility in Jul 2023; earlier some studies were halted over suspected adverse events (holds lifted Apr & Jun 2022) |
| Evorpacept* | ALX Oncology | Aspen-05 AML study paused pending dose-escalation data from Aspen-02, which earlier disappointed in MDS; both trials terminated in Aug 2023 |
| Lemzoparlimab | I-Mab | Licensed to AbbVie for $200m up front in Sep 2020; showed 70% and 50% rates of anaemia and thrombocytopenia respectively in an azacitidine combo in MDS; AbbVie discontinued trials in multiple myeloma, & AML/MDS in 2022, then terminated the tie-up in Sep 2023 |
| Maplirpacept (TTI-622/ PF-07901801)** | Pfizer (ex Trillium) | Development being focused on multiple myeloma, AML and DLBCL; ph1 trial ends Oct 2024 |
| Ontorpacept (TTI-621)** | Monotherapy trial terminated; leiomyosarcoma trial +/- doxorubicin ends Dec 2023 | |
| Letaplimab (IBI188) | Innovent | Ph1 trial terminated for lack of efficacy; ph1/2 combo with demethylating agents suspended |
| ZL-1201 | Zai Lab | Deprioritised in Aug 2022 |
| SRF231 | Coherus (ex Surface Oncology) | Discontinued after dose-limiting toxicities in dose escalation; Coherus bought Surface for $65m in Jun 2023 |
| CC-90002 | Bristol Myers Squibb (ex Celgene) | Discontinued in 2018, in favour of anti-SIRPα MAb CC-95251 |
Notes: *anti-CD47/SIRPα fusion protein; **anti-CD47/Fc fusion protein. Source: OncologyPipeline.
2729
