Eganelisib induced complete remissions and hematologic improvements as a single-agent via myeloid differentiation in a Phase 1 study in relapsed/refractory patients with myeloid malignancies (MDS/AML) who show high expression of PI3K-gamma in bone marrow blasts.

The improved overall survival in patients with high expression of PI3K-gamma in this Phase 1 study is internally consistent with the observed responses and is externally validated by the TCGA database, which suggests a poor prognosis for patients with high expression of PI3K-gamma.

Eganelisib generated a striking efficacy signal while demonstrating a favorable safety and tolerability profile in this Phase 1 study.

WALTHAM, Mass., June 2, 2026 /PRNewswire/ — Stelexis BioSciences, Inc. (Stelexis) today announced results from a Phase 1 clinical trial (NCT06533761) of eganelisib, an oral, first-in-class PI3K-gamma inhibitor, in 21 patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or higher-risk myelodysplastic syndrome (HR-MDS). The data were presented in an oral session at the 2026 ASCO Annual Meeting by Mendel Goldfinger, M.D., of Montefiore Einstein Comprehensive Cancer Center.

Key Findings

• The trial recruited a heavily pretreated patient population that was uniformly characterized by features that convey an unfavorable prognosis:
  • 29% TP53-deleted or -mutated
  • 90% abnormal cytogenetics
  • 76% received more than two prior therapies
  • 76% received prior venetoclax
• A modified objective response rate (defined as CR + Stable Disease with neutrophil count improvement) was achieved in:
  • 50% (6/12) of patients with high PI3K-gamma expression vs.
    0% (0/8) of patients with low PI3K-gamma expression (p<0.05, Fisher’s exact test), using immunohistochemical staining of bone marrow biopsies
  • Responses included molecular and major cytogenetic remissions in two patients in CR
  • Five of six responding patients had severe or life-threatening neutropenia at baseline, and all five patients demonstrated rapid neutrophil count improvements, including a rapid normalization of neutrophil counts in four patients, consistent with induction of myeloid differentiation
• Median overall survival (OS) was 27 weeks in PI3K-gamma-high patients vs. 9.9 weeks in low expressors (HR 0.22; 95% CI 0.07–0.75)

Based on historical patient data from the publicly available TCGA database, PI3K-gamma-high expression is an adverse prognostic factor for OS in patients receiving conventional therapy, thereby supporting a substantial clinical benefit observed following treatment with eganelisib in this study.

Eganelisib was well tolerated at both dose levels (45 mg and 60 mg, once daily) with no dose-limiting toxicities and no intrinsic hematologic toxicity. This is consistent with the myeloid-restricted expression of PI3K-gamma, and with the observation that PI3K-gamma is dispensable for normal hematopoiesis (Gu et al., Blood 2024).

The majority of adverse events in this study were disease-related rather than treatment-related, consistent with the underlying patient population. Treatment-related AEs were predominantly low-grade with no Grade 5 related AEs. Of note, no eganelisib-related SAEs were observed and no patient discontinued treatment due to an eganelisib-related AE.

Published outcomes for patients with relapsed/refractory disease who failed frontline venetoclax and hypomethylating agent therapy have shown a median overall survival of approximately 2.4 months (Maiti et al., Haematologica 2021), underscoring the high unmet need in this population.

“The preliminary data generated by eganelisib in patients with heavily pretreated AML and higher-risk MDS is encouraging,” said Konstantinos N. Aprilakis, M.D., Board Member at Stelexis and Partner at Deerfield Management. “In addition to a favorable safety and tolerability profile, Stelexis has observed evidence of biologic and clinical activity for eganelisib in a particularly difficult-to-treat patient population. I am especially delighted that Stelexis has identified a biomarker that may be used to identify patients most likely to benefit from treatment with eganelisib. These clinical data suggest that eganelisib has the potential to be effective across multiple hematologic malignancies of high unmet need.”

“For nearly 20 years now, the field has been searching for therapies that offer a better prognosis to MDS-patients than hypomethylating agents alone. For far too long, clinicians had to primarily rely on classifying and selecting patients for investigational treatment based on prognostic scores or bone marrow blast counts, alone. It is time we begin to classify patients based on disease-specific, functional, biological vulnerabilities and offer therapies that selectively target those biological vulnerabilities” said Manuel Aivado, MD, PhD, President and Chief Executive Officer of Stelexis BioSciences. “We believe that myeloid malignancies may find in PI3K-gamma an analog to HER2 in breast cancer, and we are thrilled that the ground-breaking discoveries of our co-founders have paved Stelexis’ way to this doorstep.”

Based on these results, Stelexis plans to advance eganelisib into a randomized expansion cohort with hypomethylating agents in treatment-naïve, PI3K-gamma-high MDS patients with an IPSS-R category of intermediate, high, or very-high risk or with CMML-2.

About Eganelisib
Eganelisib is a first-in-class, oral, highly potent, and isoform-selective inhibitor of PI3K-gamma, the myeloid-restricted isoform of the PI3K kinase family. PI3K-gamma is dispensable in normal hematopoiesis and lymphocytes, differentiating it from delta-class PI3K inhibitors that have been associated with significant immune-mediated adverse events.

In myeloid malignancies, PI3K-gamma signaling reinforces the differentiation block characteristic of AML and higher-risk MDS through PAK1, identifying PI3K-gamma as a therapeutic target whose inhibition can re-engage myeloid differentiation without imposing intrinsic myelosuppression or lymphoid toxicity.

About Stelexis
Stelexis BioSciences, Inc. is a privately held clinical-stage biopharmaceutical company developing targeted therapies for myeloid malignancies. Stelexis was founded by Deerfield Management and is headquartered in Waltham, Massachusetts.

Stelexis’ Co-Founders discovered that PAK1 is a key kinase maintaining the malignant stem cell phenotype responsible for the maturation block in patients with MDS or AML (Pandolfi et al., Blood 2015), later they identified PI3K-gamma as a core vulnerability in myeloid malignancies, and eventually showed that eganelisib-mediated inhibition of PI3K-gamma acts via inhibition of PAK1 to exert its therapeutic effects (Luo et al., Nature 2024). 

Stelexis is advancing eganelisib as a first-in-class treatment for HR-MDS and AML, and Stelexis is developing a potential best-in-class anti-IL-1RAP antibody for the treatment of Lower-Risk MDS, and other indications.

For more information, please visit www.stelexis.com.

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SOURCE Stelexis BioSciences, Inc.