8-K: Shattuck Labs Announces Positive Interim Data for SL-172154 in Blood Cancers, Prioritizes Development

Shattuck Labs reports encouraging interim results from its Phase 1B trial of SL-172154 in combination with azacitidine for higher-risk myelodysplastic syndromes and TP53 mutant acute myeloid leukemia, leading to a focus on these indications.

Summary

• Shattuck Labs has released updated interim data from its Phase 1B clinical trial of SL-172154 combined with azacitidine.
• The trial focuses on patients with frontline higher-risk myelodysplastic syndromes (HR-MDS) and TP53 mutant acute myeloid leukemia (AML).
• In HR-MDS patients, the objective response rate (ORR) was 67%, with an initial complete remission (CR)/marrow complete remission (mCR) rate of 58%.
• For TP53 mutant AML patients, the ORR was 43%, with a 33% CR/complete remission with incomplete hematologic recovery (CRi).
• Median overall survival has not been reached in either group.
• SL-172154 demonstrated a manageable safety profile in combination with azacitidine.
• The company is now focusing clinical development on HR-MDS and TP53m AML due to promising results and potential for faster approval.
• Enrollment is underway for a randomized, controlled HR-MDS cohort.
• Shattuck is not planning further development in platinum-resistant ovarian cancer (PROC) due to the competitive landscape and lack of benefit beyond existing treatments.

Sentiment

Score: 8

Explanation: The document presents very positive clinical data for SL-172154 in HR-MDS and TP53m AML, with high response rates and a manageable safety profile. The strategic focus on these indications and the potential for accelerated approval are also positive. The decision to discontinue development in PROC is a minor negative, but overall the sentiment is very positive.

Positives

• The 67% objective response rate in HR-MDS patients is very promising, especially with a 58% complete remission rate.
• The 43% objective response rate in TP53 mutant AML patients is also encouraging, with a 33% complete remission rate.
• The median overall survival not being reached in either group suggests a potential for long-term benefit.
• The manageable safety profile of SL-172154 is a positive sign.
• The company's focus on HR-MDS and TP53m AML could lead to faster regulatory approval.
• The ongoing randomized, controlled HR-MDS cohort is a positive step for further development.

Negatives

• In the platinum-resistant ovarian cancer (PROC) study, the combination of SL-172154 with Elahere did not show an ORR benefit beyond Elahere alone.
• There were some Grade 3/4 adverse events reported in both the HR-MDS and TP53m AML groups, including infusion-related reactions, neutropenia, and thrombocytopenia.
• There were a few deaths due to adverse events, although these were deemed unrelated to SL-172154.

Risks

• The clinical trial is still in Phase 1B, and further trials are needed to confirm the efficacy and safety of SL-172154.
• The company is discontinuing development in PROC, which could impact the overall pipeline.
• There are risks associated with clinical trials, including the potential for adverse events and the possibility that the drug may not be effective.
• The company's future success depends on the successful development and commercialization of SL-172154.
• The competitive landscape in cancer therapeutics is constantly evolving.

Future Outlook

Shattuck plans to focus on clinical development of SL-172154 in HR-MDS and TP53m AML, with ongoing enrollment in a randomized, controlled HR-MDS cohort and plans to engage in regulatory discussions later this year regarding the registrational strategy. The company will continue to follow patients for progression-free survival and overall survival.

Management Comments

• Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck, stated that the data further supports the differentiated mechanism of action of SL-172154 and its emergence as a leading CD47 inhibitor.
• Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck, expressed encouragement by the maturing data and the manageable safety profile of SL-172154.

Industry Context

This announcement is significant as it highlights the potential of SL-172154 as a novel treatment for high-risk blood cancers. The focus on HR-MDS and TP53m AML, which have limited treatment options, positions Shattuck to address unmet medical needs. The decision to discontinue development in PROC reflects a strategic shift towards areas with higher potential for success and faster regulatory pathways.

Comparison to Industry Standards

• The 67% ORR in HR-MDS patients is notably higher than the 4% ORR reported with PLD alone in the Javelin-200 study for ovarian cancer, suggesting a significant improvement with the addition of SL-172154.
• While specific benchmarks for combination therapies in HR-MDS and TP53m AML are not provided, the reported ORR and CR rates are promising compared to historical outcomes with azacitidine alone, which typically show lower response rates and shorter durations of remission.
• The company is positioning SL-172154 as a leading CD47 inhibitor, which is a competitive space with other companies developing similar therapies. The data suggests that SL-172154 may have a differentiated mechanism of action and improved efficacy compared to other CD47 inhibitors.

Stakeholder Impact

• Shareholders will likely react positively to the strong clinical data and the company's strategic focus.
• Patients with HR-MDS and TP53m AML may benefit from a new treatment option.
• Employees may be motivated by the positive results and the company's focus on these indications.
• The decision to discontinue development in PROC may impact stakeholders involved in that program.

Next Steps

• Shattuck will continue enrollment in the randomized, controlled HR-MDS cohort.
• The company plans to engage in regulatory discussions regarding the registrational strategy for SL-172154 later this year.
• Shattuck will continue to follow patients for progression-free survival and overall survival.
• The company will make the EHA poster available on its website.

Key Dates

Keywords

SL-172154, HR-MDS, TP53m AML, Clinical Trial, Azacitidine, Cancer, Hematologic Malignancies, CD47, CD40, Objective Response Rate, Complete Remission, Bi-functional Fusion Protein