SELLAS Presents Preclinical Efficacy of SLS009 in ASXL1 Mutated Colorectal Cancer at 2025 ASCO Annual Meeting
- Strong preclinical efficacy with 50% of ASXL1 mutant cell lines showing potent response
- High response rate (75%) in cell lines with ASXL1 frameshift mutations
- Effective concentrations below safety thresholds, indicating favorable therapeutic window
- Large market potential with 22,500 new colorectal cancer cases with high microsatellite instability annually in US
- Only preclinical data presented, requiring further clinical validation
- Limited efficacy in wild-type cell lines (0% response rate)
- Treatment may only be effective for specific mutation types
Insights
SLS009 shows promising preclinical efficacy against ASXL1-mutated colorectal cancer, potentially expanding tambiciclib's applications beyond its current AML trials.
The preclinical data presented by SELLAS at ASCO 2025 reveals a compelling efficacy profile for SLS009 (tambiciclib) specifically in colorectal cancer cell lines harboring ASXL1 mutations. The results demonstrate remarkable selectivity, with 50% of ASXL1-mutant cell lines showing high sensitivity (IC50<100 nM) compared to zero response in wild-type lines. This selectivity becomes even more pronounced in cells with frameshift mutations, where 75% responded at these low concentrations.
What's particularly noteworthy is the steep dose-response curve observed in sensitive cell lines, with 75% of responsive cells showing IC99 values below 100 nM. This suggests robust and complete growth inhibition at clinically achievable concentrations. The fact that effective concentrations fall well below those already deemed safe in clinical settings indicates a favorable therapeutic window - crucial for balancing efficacy against toxicity.
The potential market is substantial, with approximately 12,375 patients annually in the US alone (calculated from the 22,500 high microsatellite instability colorectal cancers with 55% ASXL1 mutation frequency). ASXL1 mutations appear to function as a predictive biomarker for response, which could enable precision medicine approaches with companion diagnostics.
The company is sensibly leveraging their existing Phase 2 AML program to build a broader oncology franchise targeting ASXL1-driven malignancies. While these remain preclinical findings that require validation in human trials, the data provides a strong mechanistic rationale for expanding tambiciclib's development into colorectal cancer indications.
- ASCO Presentation Supports SLS009 as a Potential Targeted Therapy for ASXL1 Mutated Colorectal Cancer –
- 22,500 New Cases of Colorectal Cancer with High Microsatellite Instability per Year in the US:
NEW YORK, June 02, 2025 (GLOBE NEWSWIRE) -- SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) (“SELLAS” or the “Company”), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, today announced preclinical efficacy of SLS009 (tambiciclib) in ASXL1 mutated colorectal cancer lines. The data are featured in a presentation, entitled “In vitro efficacy of CDK9 inhibitor tambiciclib (SLS009) in ASXL1 mutated colorectal cancer cell lines” at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30- June 3, 2025, in Chicago, Illinois.
In a panel of cell lines, SLS009 demonstrated potent anti-proliferative activity:
- In
50% (4/8) of ASXL1 mutant cell lines showed an IC50<100 nM, compared to0% (0/4) of ASXL1 wild-type lines - Among cell lines harboring ASXL1 frameshift mutations (FSMs),
75% (3/4) responded with IC50 <100 nM versus only12.5% (1/8) in cell lines without FSMs - All cell lines (3/3) with ASXL1 FSMs in the 637-638 protein region responded to treatment with SLS009
- In cell lines with IC50 <100 nM,
75% (3/4) also demonstrated IC99 values below 100 nM, indicating steep dose response curve - Importantly, effective concentrations were significantly lower than those achieved in patients treated at the recommended phase 2 dose determined to be safe, suggesting a broad therapeutic window.
“These results provide strong rationale for continued advancement of SLS009 as a potential treatment for ASXL1-mutated cancers,” said Dr. Dragan Cicic, Senior Vice President, Chief Development Officer at SELLAS. “The ability to selectively target ASXL1-driven tumors at concentrations well below the known safety threshold opens the door for tolerable and effective therapy. Based on the findings, we believe that ASXL1 mutation status could serve as a potential biomarker for response to SLS009 inhibition, which may allow us to further refine patient selection and improve outcomes. We look forward to presenting these results at ASCO.”
| Poster presentation details: | ||
| Title: | In vitro efficacy of CDK9 inhibitor tambiciclib (SLS009) in ASXL1 mutated colorectal cancer cell lines | |
| Session Date and Time: | Monday, June 2, 2025, 1:30 PM-4:30 PM CDT | |
| Session Title: | Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology | |
| Location: | Hall A - Posters and Exhibits | |
| Abstract #: | 3121 | |
| Poster Board #: | 436 | |
SLS009 is currently being investigated in a Phase 2 open-label, single-arm, multi-center study designed to evaluate the safety, tolerability, and efficacy of SLS009 in combination with venetoclax and azacitidine including AML patients with ASXL1 mutations. Initial clinical safety and efficacy data are available. In addition, the study aims to identify biomarkers for the target patient population and enrichment for further trials. For more information on the study, visit clinicaltrial.gov identifier NCT04588922.
About SELLAS Life Sciences Group, Inc.
SELLAS is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, GPS, is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein, which is present in an array of tumor types. GPS has the potential as a monotherapy and combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing SLS009 (tambiciclib) - potentially the first and best-in-class differentiated small molecule CDK9 inhibitor with reduced toxicity and increased potency compared to other CDK9 inhibitors. Data suggests that SLS009 demonstrated a high response rate in AML patients with unfavorable prognostic factors including ASXL1 mutation, commonly associated with poor prognosis in various myeloid diseases. For more information on SELLAS, please visit www.sellaslifesciences.com.
Forward-Looking Statements
This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, forward-looking statements can be identified by terminology such as “plan,” “expect,” “anticipate,” “may,” “might,” “will,” “should,” “project,” “believe,” “estimate,” “predict,” “potential,” “intend,” or “continue” and other words or terms of similar meaning. These statements include, without limitation, statements related to the GPS clinical development program, including the REGAL study and the timing of future milestones related thereto. These forward-looking statements are based on current plans, objectives, estimates, expectations, and intentions, and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties with oncology product development and clinical success thereof, the uncertainty of regulatory approval, and other risks and uncertainties affecting SELLAS and its development programs as set forth under the caption “Risk Factors” in SELLAS’ Annual Report on Form 10-K filed on March 20, 2025 and in its other SEC filings. Other risks and uncertainties of which SELLAS is not currently aware may also affect SELLAS’ forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof. SELLAS undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations, or other circumstances that exist after the date as of which the forward-looking statements were made.
Investor Contact
Bruce Mackle
Managing Director
LifeSci Advisors, LLC
FAQ
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