By Connor Lynch

Pictured: Doctor holding up hand to stop, courtesy of iStock
Clinical-stage oncology company ALX Oncology is dropping trials for two of its anti-CD47 programs after disappointing efficacy findings.
In its second-quarter earnings report on Thursday, the San Francisco-based company announced an end to its ASPEN-02 and ASPEN-05 programs, which were evaluating the efficacy of its CD47-inhibitor evorpacept. The protein works by binding to receptors on cancer cells that can potentially enhance the action of both chemotherapy drugs, as well as the body's natural immune response.
The two programs were assessing the effectiveness of evorpacept in concert with chemotherapy drugs to treat myelodysplastic syndrome and acute myeloid leukemia, respectively. Initial findings were promising. The combination of evorpacept and chemotherapy drugs—Bristol Myer Squibb’s azacitidine and AbbVie and Genentech’s venetoclax—proved more effective in combination than apart in early trials for myelodysplastic syndrome, as well as acute myeloid leukemia.
However, later findings in the ASPEN-02 trial led ALX to reconsider “as the evorpacept combination did not substantially improve upon the historical activity of azacitidine alone” in the 45 patients being tested, the report said. In addition, because of the “close mechanism of action with azacitidine” in the two cancers, the company decided not to pursue the ASPEN-05 program any further either.
“Based upon this decision, resources originally earmarked for these trials will be allocated to support the company’s ongoing programs evaluating combinations with anti-cancer antibodies and PD-1/PD-L1 immune checkpoint inhibitors,” ALX said.
CEO Jaume Pons said the company remains “steadfast" in its "conviction that the primary mechanism of action of evorpacept is unique compared to other CD47 blockers when combined with anti-cancer antibodies, ADCs, or immune checkpoint inhibitors.”
ALX is going ahead with its Phase II ASPEN-06 trial, evaluating the efficacy of evorpacept in concert with Herceptin, CYRAMZA, and paclitaxel for patients with HER-2-positive gastric and gastroesophageal junction cancers, as well as its Phase II testing evorpacept with KEYTRUDA, and a Phase I/II trial testing it with SARCLISA.
The news comes only weeks after Gilead Sciences ended Phase III trials of its own anti-CD47 investigation focusing on magrolimab “due to futility based on a planned analysis.” The monoclonal antibody was an ambitious target and big risk for the company, which spent just shy of $5 billion acquiring Forty Seven and its lead candidate.
These companies are not alone in running into trouble investigating CD47-based treatments. AbbVie pulled out of its partnership with I-Mab in August 2022 to study lemzoparlimab, while Chinese-biotech Zai Lab deprioritized its own candidate that same month citing the “competitive landscape.”
Meanwhile, Forty Seven's founders have pursued other avenues, launching Bitterroot Bio to investigate anti-CD47 heart medications and receiving backing from major donors such as ARCH, Deerfield, and GV, Google’s venture capital arm.
Connor Lynch is a freelance writer based in Ottawa, Canada. Reach him at lynchjourno@gmail.com.