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EHA 2024 preview – Shattuck has a heart scare

An early study of the group’s anti-CD47 project SL-172154 has seen waning efficacy, a heart attack and a death.

Previous attempts to hit CD47 have disappointed, but Shattuck Labs’ SL-172154 was supposed to be different. However, early data on the project, released yesterday in an abstract for the upcoming European Hematology Association conference, have clearly got investors worried that history is repeating itself, and the group’s shares sank 18%.

Probably the most worrying finding was that two of 39 patients receiving SL-154 had serious cardiovascular events: one grade 4 myocardial infarction and one fatal cardiac arrest. The project had been designed to sidestep the risk of cytopenias that have dogged earlier CD47 inhibitors like Gilead’s magrolimab – but if these have been replaced by cardiac toxicity this will be bad news for Shattuck.

While both events were deemed possibly related to SL-154, the abstract notes that both patients had a history of “significant cardiovascular disease ... and other comorbidities”. And Shattuck previously disclosed the death last December when it reported initial results from the same phase 1 study, in first-line high-risk myelodysplastic syndrome (MDS) and TP53 mutant acute myeloid leukaemia (AML). 

More details could come at EHA, and these will be closely watched.

MDS better than AML?

On the efficacy side, meanwhile, responses with SL-154 plus azacitidine have fallen slightly since that previous update, with the addition of more patients.

There’s still reason for optimism in MDS, where SL-154 continues to exceed the response rate target that Shattuck previously set

 

Expectation vs reality: data on Shattuck’s SL-172154 in AML & MDS

Setting/trialDec 2023 dataEHA 2024 dataPre-readout goal
1L TP53m AML + azacitidine (NCT05275439)27% CR/CRi (3/11 pts)21% CR/CRi (3/14 pts)>30% CR/CRi & >6mo DoR
1L HR-MDS + azacitidine (NCT05275439)64% CR/mCR (9/14 pts)61% CR/mCR (14/23 pts)>40% CR/mCR & >9mo DoR

Note: Data cutoff 1 Feb 2024, median duration of response and overall survival not reached by this date; poster to be presented 14 June with later data cutoff. Source: EHA abstract.

 

But in AML the project is falling short, with the EHA abstract showing no further responses since December. Evercore ISI analysts noted that most of the additional patients were enrolled in January and February, so didn’t have long to reach a response by the abstract cutoff date of 1 February.

The EHA poster will have a cutoff date “in the late second quarter of 2024”, according to Shattuck, which might allow for an improving response rate. But some investors aren’t sticking around to find out if the numbers will move in the right direction.

Shattuck has previously said that phase 3 development of SL-154 would start in early 2025 in high-risk MDS and TP53-mutant AML. However, it made no mention of this in its first-quarter earnings release earlier this month. 

At the time of publication Shattuck hadn’t responded to questions from ApexOnco about its pivotal plans but, with results in AML disappointing, it seems possible that the group could focus on MDS. Still, even decent efficacy here will come to nothing if further signals of cardiotoxicity emerge.

The 2024 EHA Congress will take place on 13-16 June in Madrid, Spain.

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