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CD47 fell into druggivability questions, and another company withdrew from the CD47 track
.
Recently (January 13, 2023), Arch Oncology, which focuses on CD47 development, announced that it has terminated its research and development work on anti-CD47 antibodies, and most of the company's employees have left
.
Arch Oncology was one of the first companies to deploy CD47 targets, and AO-176 is the company's most advanced pipeline
.
According to the company's departing employees, Arch Oncology has canceled clinical development
of AO-176.
AO-176 is a highly differentiated anti-CD47 antibody that, in addition to blocking the CD47/SIRPα signaling pathway, preferentially binds to tumor cells rather than normal cells
.
It also binds tumors
more effectively in an acidic microenvironment (low pH).
What's more, AO-176 also directly kills tumor cells, not ADCC
.
AO-176 has progressed to clinical phase I/II
.
of macrophages.
On the surface of all cancer cells, high expression of CD47 can be found, and cancer cells use the mechanism of action between CD47 and macrophages to escape macrophage phagocytosis
.
This broad-spectrum characteristic makes the industry believe that it will have great achievements in the field of oncology and become one of
the star targets of tumor immunity.
Although the application prospect is broad, hemotoxicity has always been a safety hazard
that is difficult to avoid in the clinical application of CD47-targeted drugs.
In addition to tumor cells, CD47 is also widely expressed on the surface of red blood cells, and drugs targeting CD47 inevitably accidentally damage red blood cells, resulting in phagocytosis destruction and agglutination
of red blood cells.
The first batch of companies to try to develop it was therefore clinical
.
In 2017, Arch Oncology announced the termination of a phase I/II clinical trial of CD47 monoclonal antibody Ti-061 for solid tumors due to the death of the first patient enrolled in the trial two days after receiving treatment, mainly due to red blood cell agglutination
.
In July 2018, Celgene also announced the termination of phase I clinical treatment of CD47 monoclonal antibody CC-90002, which also experienced serious adverse reactions of hematotoxicity (including decreased red blood cell and platelet counts).
。 Since then, the industry has seriously questioned
the drug value of CD47 drugs.
Until 2019, the good performance of leading player Forty Seven's magrolimab at the ASH conference made everyone regain confidence in the development of CD47, and development activities began to recover, leading a number of enterprises to enter the market
.
CD47 development is deadlocked
However, safety concerns have always been present, and the news of several clinical suspension of CD47 products last year has once again called into questionits druggability.
At the beginning of 2022, Gilead Magrolimab combined with azacitidine clinical trial, suspected of unexpected serious adverse reactions (SUSAR) had a significant imbalance between the study groups, and was announced by the FDA to be suspended
.
The new report of blood toxicity has investors worried
about Magrolimab's future.
Later, after comprehensive analysis of the safety data of various clinical trials, some clinical trials of magrolimab combined with azacitidine were terminated
by the FDA.
Zai Lab canceled its Phase II trial program for its CD47 monoclonal antibody ZL-1201 after reviewing the CD47 competitive landscape, reducing its priority
in its pipeline.
AbbVie revised its previous $1.
94 billion licensing agreement with I-Mab for Lemzoparlimab, electing to terminate the Phase I clinical trial of "Lemzoparlimab + azacitidine + venetoclax" in myelodysplastic syndrome and acute myeloid leukemia, and is pinning its future on other CD47 antibody drug
candidates.
Summary
The development of CD47 is still mired in doubts about druggability, safety issues have always been on the road to CD47 development, and how to maximize the killing of tumor cells while protecting red blood cells is still the core ofCD47 drug development.
Reference source:
https://endpts.com/scoop-roche-backed-startup-gives-up-on-cd47-as-ceo-most-employees-leave/ tens of billions of dollars to enter the gambling, the lure of CD47 targets and "traps"/amino finance
Note: This article does not contain any medical views or investment advice
