Fewer players are still at the CD47 table.
Four months ago, another CD47 player exited the stage. In its Q1 2026 earnings and latest pipeline update, Pfizer removed maplirpacept, a CD47 drug candidate, from its development portfolio. With that, the entire CD47 program Pfizer acquired from Trillium for $2.3 billion has now been written off.
Going forward, it's possible that more players will exit the field. A review of the latest semi-annual reports of Hong Kong-listed pharmaceutical companies reveals that some CD47 molecules that were once heavily promoted are now being mentioned less frequently in financial reports and promotional materials.
At present, for pharmaceutical companies that are still holding on, whether CD47 is still worth pursuing and how to move forward is a question that must be considered.
Fortresses Fall One by One
Over the past decade, the CD47 field has been continuously iterating and upgrading, but no molecule has been able to clearly prove itself in clinical settings.
The standout is Gilead's magrolimab.
In 2020, Gilead acquired FortySeven for approximately $4.9 billion, bringing magrolimab into its portfolio, which was then the fastest-progressing CD47 antibody globally. The drug had also shown a high overall response rate of up to 91% in early trials for MDS and AML when combined with azacitidine, generating significant expectations.
In terms of design, magrolimab uses an IgG4-type antibody, which reduces binding to Fc receptors, minimizes non-specific activation, and utilizes a dose-escalation administration strategy, aiming to address the anemia issue caused by the high expression of CD47 on normal red blood cells.
However, once it actually entered clinical research, it was found that magrolimab's optimization was far from sufficient. The ENHANCE-3 study showed that in AML patients who had not previously received intensive chemotherapy and were treated with azacitidine + venetoclax, the addition of magrolimab did not improve overall survival and even increased the risk of death.
Based on safety risks and poor efficacy, Gilead has submitted an application to discontinue magrolimab.
This is still just the beginning—2025 will be CD47's darkest hour. Overseas, the most closely watched "fortresses" of CD47 have fallen one after another.
In April, ALX Oncology announced that its CD47 inhibitor Evorpacept failed to meet primary endpoints in two Phase II clinical trials, ASPEN-03 and ASPEN-04, when used in combination with K drugs. Previously, the company had terminated clinical trials of Evorpacept for MDS and AML.
The following June, Pfizer announced that its acquired CD47-targeting drug maplirpacept would halt a Phase II study in relapsed/refractory diffuse large B-cell lymphoma due to difficulty in patient recruitment. Earlier, another CD47 asset, ontorpacept, had already disappeared from the company's pipeline.
The collapse of these "strongholds" once left the CD47 track in a state of confusion.
Nubia's 'Don't Eat Me' Slogan Not as Simple as it Sounds
The core dilemma of the CD47 target lies in the balance between toxicity and efficacy, which is difficult to achieve, and this is also the common reason for the failure of these heavyweight products.
Many molecules are being upgraded based on the CD47 dilemma, but the effect is not ideal.
For instance, Pfizer's maplirpacept attempted to reduce toxicity through SIRPα-IgG4 fusion protein, but the overly weakened binding affinity resulted in insufficient efficacy, leading to the adoption of high-dose administration.
In clinical settings, the maximum doses of ontopacept and maplirpacept were 2 mg/kg and 24 mg/kg, respectively. Although maplirpacept resulted in fewer ≥3-grade adverse events than ontopacept in clinical results, 30% of patients still experienced thrombocytopenia.
The strategy of completely inactivating Fc is also not viable. ALX Oncology's evorpacept is a typical example, which retains a high-affinity CD47 binding structure while using an inactivated Fc, with the goal of reducing Fc-mediated effects related to normal red blood cells, thereby improving the safety of traditional CD47 antibodies.
However, the safer design did not lead to better efficacy. The study of Evorpacept in combination with K drug for the treatment of head and neck squamous cell carcinoma also failed to meet the primary endpoint.
Arch Oncology's AO-176 is also a CD47 antibody targeting the IgG2 Fc region, which does not activate ADCC but has direct cytotoxic effects, with minimal impact on hematological parameters in non-human primates and no observed transient anemia. However, interim data from the phase I/II clinical trial of AO-176 showed that 33% of patients developed thrombocytopenia, including 22% with grade 3 transient thrombocytopenia, and 22% developed anemia.
It is clear that under the "don't eat me" mechanism, the balance line between efficacy and toxicity has always been a hurdle that CD47 drugs cannot overcome. As batch after batch of optimized molecules fail, the clinical value of CD47 is also repeatedly called into question.
Retreat or Advance
After Pfizer and other contenders fell one after another, whether to retreat or continue forward has become a crucial question for all those who insist on persevering.
Currently, a number of players are still actively exploring CD47, and some positive signals have indeed emerged.
Evorpacept is a typical representative of combination therapy. Due to the inactivation of the Fc segment, Evorpacept has almost no single-drug activity, such as ADCC, ADC, and CDC effects, and cannot trigger macrophages to phagocytose tumors. Therefore, combination therapy must be adopted, relying on other monoclonal antibodies or ADC drugs used in combination to provide an "eat me" activation signal, further exerting an immune effect.
In the randomized Phase II ASPEN-06 trial, evorpacept was combined with trastuzumab, ramucirumab, and paclitaxel to treat HER2-positive gastric cancer/gastroesophageal junction cancer that had previously been treated with anti-HER2 therapy.
2025 updated data shows that in patients with confirmed HER2 positivity, the ORR reached 48.9%, compared to 24.5% in the control group, and the mDOR was 15.7 months versus 9.1 months. However, the FDA did not give high praise, as the indication still has Enhertu as a major competitor.
There are also many domestic players holding on.
Kangfang Bio's AK117 has also been optimized, positioning it as a new generation of CD47 antibodies, addressing issues such as red blood cell agglutination faced by traditional CD47 antibodies through molecular design.
In 2026, EHA announced the AK117-206 study, a randomized, double-blind, placebo-controlled Phase II trial, in which 60 newly diagnosed AML patients who were not suitable for intensive chemotherapy received AK117 (or placebo) + azacitidine + venetoclax. The data showed that the ORR for the AK117 group was 80.0%, compared to 66.7% for the control group. The CRc rate was 56.7% versus 53.3% for the placebo group, with a median duration of CRc of 10.4 months versus 6.5 months, demonstrating a significant advantage.
However, the details are still worth noting. The duration of CRc in the placebo group was 6.5 months, but in the clinical data for standard AML treatment (VIALE-A), the duration was 14.7 months, with the current control group being significantly weaker than in the past. Although this is based on differences in patient baseline conditions, the data still raises questions about the value of AK117.
Safety issues are also not to be ignored. In the study, the incidence rates of ≥3-grade treatment-emergent adverse events (TEAEs) in the two treatment groups were 96.7% and 93.3%, respectively, with 43.3% of patients in both groups reporting ≥3-grade anemia. This suggests that AK117 did not significantly exacerbate anemia, but also failed to eliminate the inherent hematologic toxicity burden of CD47-class drugs.
Kangfang Bio is currently conducting three Phase III clinical trials for the combination of AK117 and AK112, making it one of the fastest-progressing players in the CD47 field.
In terms of progress, another comparable one is Yimeng Bio's IMM01, an IgG1 Fc fusion protein that reduces its binding affinity to red blood cells by introducing mutations in the D1 domain and removing glycosylation sites.
IMM01 in combination with azacitidine for the treatment of CMML showed a Phase II clinical data ORR of 72.7% (compared to 37.5% in the control group), with a CR rate of 27.3%, significantly higher than the 8.3% in the control group.
On July 16, 2026, Eucure Biotech announced that the Phase III clinical trial of IMM01 in combination with azacitidine for the treatment of newly diagnosed CMML has completed enrollment of all 173 patients, with progress comparable to that of AK117.
The efforts of these adherents may bring some new hope to the CD47 field, or perhaps it will be another disappointment.
Don't Be Fooled by the 'Next-Gen PD-1' Narrative
The future of CD47 may be bright, but the road ahead is bound to be tortuous. So far, CD47 has taught us a valuable lesson - not to be blinded by the "next-generation PD-1" narrative.
Following the success of PD-1, the industry has come to realize that tumor immunotherapy is not just about attacking, but also about applying the "brakes", which is also an important approach.
Research has found that like T cells, macrophages also have a "brake". As a result, the CD47 "don't eat me" signal has been developed into a new tumor treatment immune checkpoint. For a time, CD47 was seen as one of the most promising immune targets after PD-1.
In hindsight, however, the immune system proved to be too complex.
Firstly, CD47 is not a simple immune "switch". Existing research indicates that CD47 does not merely transmit a "don't eat me" signal through SIRPα, but rather is widely present on the surface of human cells and interacts with multiple receptors and signaling pathways, including SIRPα, integrin, VEGFR2, CD36, and FAS.
Furthermore, a summary of multiple studies found that CD47 drugs induced tumor immune suppression in humans, which was far less effective than the antitumor activity observed in animal models such as mice.
A recent 2026 study in Science also revealed the complexity of CD47 in hematological tumors.
A research team used human AML cells and human macrophages to conduct a genome-wide CRISPR screen, and found that CD47 had a pronounced inhibitory effect on phagocytosis by mouse macrophages, but this effect was very limited in human macrophages.
Further research found that CD43 on the surface of AML cells, as well as its O-glycosylation and sialylation, are important mechanisms that restrict the phagocytosis of human macrophages. This suggests that in the human system, the control of the "don't eat me" signal of macrophages may not be limited to just the CD47-SIRPα pathway.
Various studies have shown that CD47 is far more complex than previously imagined, and in the past, the unknown aspects of it were obscured by the narrative of being the "next-generation PD-1".
This may be the most perilous moment in innovative drug development, not when a target fails, but when the industry is overly optimistic about a target, to the point of ignoring the risks that it inherently possesses.