SELLAS Announces Positive Data from Preclinical Studies Indicating ASXL1 Mutations as Predictor of Response to SLS009 in Solid Cancers
SELLAS Life Sciences Group announced promising preclinical study results showing ASXL1 mutations as a key predictor of SLS009 response in solid cancers. The study revealed high efficacy in 67% of ASXL1 mutated solid cancers compared to 0% in non-ASXL1 mutated cancers. In colorectal cancer (CRC MSI-H), ASXL1 mutations were found in 58% of cases, with high efficacy in 57% of mutated cell lines. In non-small cell lung cancer (NSCLC), 100% efficacy was observed in ASXL1 mutated cell lines. SLS009 outperformed the positive control in 5 out of 9 cell lines, positioning it as a promising therapeutic candidate.
Il gruppo SELLAS Life Sciences ha annunciato risultati promettenti di uno studio preclinico che mostrano le mutazioni ASXL1 come un importante predittore di risposta a SLS009 nei tumori solidi. Lo studio ha rivelato un'alta efficacia nel 67% dei tumori solidi con mutazioni ASXL1 rispetto al 0% nei tumori senza mutazioni ASXL1. Nel cancro colorettale (CRC MSI-H), le mutazioni ASXL1 sono state trovate nel 58% dei casi, con un'alta efficacia nel 57% delle linee cellulari mutate. Nel carcinoma polmonare non a piccole cellule (NSCLC), è stata osservata un'efficacia del 100% nelle linee cellulari mutate ASXL1. SLS009 ha superato il controllo positivo in 5 su 9 linee cellulari, posizionandosi come un promettente candidato terapeutico.
El grupo SELLAS Life Sciences anunció resultados prometedores de un estudio preclínico que muestra que las mutaciones de ASXL1 son un predictor clave de respuesta al SLS009 en cánceres sólidos. El estudio reveló una alta eficacia en el 67% de los cánceres sólidos con mutaciones de ASXL1 en comparación con el 0% en cánceres sin mutaciones de ASXL1. En el cáncer colorrectal (CRC MSI-H), se encontraron mutaciones de ASXL1 en el 58% de los casos, con alta eficacia en el 57% de las líneas celulares mutadas. En el cáncer de pulmón no microcítico (NSCLC), se observó una eficacia del 100% en las líneas celulares mutadas de ASXL1. SLS009 superó al control positivo en 5 de 9 líneas celulares, posicionándose como un prometedor candidato terapéutico.
SELLAS 생명과학 그룹은 ASXL1 돌연변이가 고형 암에서 SLS009 반응의 주요 예측 인자라는 것을 보여주는 유망한 전임상 연구 결과를 발표했습니다. 연구는 ASXL1 돌연변이를 가진 고형 암에서 67%의 높은 효능을 나타낸 반면, 비 ASXL1 돌연변이를 가진 암에서는 0%의 효능을 보였습니다. 결장암(CRC MSI-H)에서 ASXL1 돌연변이는 58%의 사례에서 발견되었고, 돌연변이 세포주에서 57%의 높은 효능을 보였습니다. 비소세포폐암(NSCLC)에서 ASXL1 돌연변이를 가진 세포주에서는 100%의 효능이 관찰되었습니다. SLS009은 9개의 세포주 중 5개에서 양성 대조군을 능가하여 유망한 치료 후보로 자리매김하고 있습니다.
Le groupe SELLAS Life Sciences a annoncé des résultats précliniques prometteurs montrant que les mutations ASXL1 sont un indicateur clé de la réponse à SLS009 dans les cancers solides. L'étude a révélé une efficacité élevée de 67% des cancers solides mutés ASXL1, contre 0% dans les cancers sans mutations ASXL1. Dans le cancer colorectal (CRC MSI-H), des mutations ASXL1 ont été trouvées dans 58% des cas, avec une efficacité élevée dans 57% des lignées cellulaires mutées. Dans le cancer du poumon non à petites cellules (NSCLC), une efficacité de 100% a été observée dans les lignées cellulaires mutées ASXL1. SLS009 a surpassé le contrôle positif dans 5 des 9 lignées cellulaires, se positionnant comme un candidat thérapeutique prometteur.
Die SELLAS Life Sciences Group gab vielversprechende präklinische Studienergebnisse bekannt, die zeigen, dass ASXL1-Mutationen ein wichtiger Prädiktor für die Reaktion auf SLS009 bei soliden Tumoren sind. Die Studie ergab eine hohe Wirksamkeit bei 67% der ASXL1-mutierten soliden Tumoren im Vergleich zu 0% bei nicht-ASXL1-mutierten Tumoren. Bei Dickdarmkrebs (CRC MSI-H) fanden sich ASXL1-Mutationen in 58% der Fälle, mit einer hohen Wirksamkeit von 57% der mutierten Zelllinien. Bei nicht-kleinzelligem Lungenkrebs (NSCLC) wurde eine Wirksamkeit von 100% in ASXL1-mutierten Zelllinien beobachtet. SLS009 übertraf die positive Kontrolle in 5 von 9 Zelllinien und positioniert sich als vielversprechender therapeutischer Kandidat.
- High efficacy (67%) observed in ASXL1 mutated solid cancers
- SLS009 outperformed positive control in 5/9 cell lines
- 100% efficacy in ASXL1 mutated NSCLC cell lines
- Patent filing for ASXL1 mutations as predictive diagnostic
- No response in non-ASXL1 mutated cancer cell lines
- sample size in NSCLC study (only 6 cell lines)
Insights
The preclinical data for SLS009 demonstrates compelling efficacy in ASXL1-mutated solid cancers, with significant implications for targeted cancer therapy. The
The low IC50 threshold of <100 nM, significantly below the standard <1,000 nM benchmark, indicates exceptional potency. SLS009's ability to outperform staurosporine in 5/9 cell lines further validates its potential. The patent filing for ASXL1 mutation as a predictive diagnostic strengthens the company's intellectual property position and could lead to a companion diagnostic development.
This data represents a significant advancement in precision oncology. The identification of ASXL1 mutations as a predictive biomarker for solid tumors is particularly valuable, as it could enable better patient selection and potentially higher success rates in clinical trials. The high prevalence of ASXL1 mutations in CRC MSI-H (
The superior performance compared to revumenib and staurosporine indicates strong therapeutic potential. The established safety profile from AML trials provides a solid foundation for expanding into solid tumors, potentially accelerating the development timeline. This targeted approach could significantly improve treatment outcomes in previously difficult-to-treat solid cancers.
- Preselection Method for Cancers Responding to SLS009: High Efficacy of SLS009 Observed in
- ASXL1 Mutations Predictably Identified in Colorectal Cancer (CRC MSI-H) and Non-Small Cell Lung Cancer (NSCLC) in Addition to Hematologic Malignancies -
- Existing Clinical Data Demonstrating SLS009 Efficacy in ASXL1 mutated AML and Safety Across Multiple Cancer Types Lay Foundation for Targeted SLS009 Clinical Trial in Selected Solid Cancers -
NEW YORK, Nov. 27, 2024 (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 data from preclinical studies identifying ASXL1 mutation as key predictor of SLS009, a highly selective CDK9 inhibitor, response in solid cancers.
Based on elucidated biology of ASXL1 mutations, results from SELLAS’ clinical trials in acute myeloid leukemia (AML), and reports of common occurrence of ASXL1 mutations in some solid cancers, the Company performed experiments and analyses to explore the following:
- The frequency of ASXL1 mutations in certain solid cancers, including colorectal carcinomas (CRC) with high level microsatellite instability (MSI-H) and non-small cell lung cancer (NSCLC)
- Whether ASXL1 mutations in solid cancers may predict as high SLS009 efficacy as the efficacy exhibited in AML where ASXL1 and similar mutations demonstrated high response rates in SELLAS’ clinical trials
SELLAS performed experiments in patient derived cell lines (PDCs) exposing them to SLS009 at various concentrations and determining the inhibitory concentration (IC50) for each cell line. All cell lines were analyzed for presence of ASXL1 mutations and other genetic markers. High efficacy was prespecified as IC50 < 100 nM, significantly lower than the standard threshold definition for an effective compound (IC50 < 1,000 nM). This threshold was chosen based on the observed long-lasting concentrations of SLS009 observed in patients, which were ~400 nM.
Negative controls consisted of untreated cell lines, while active negative control varying concentrations of revumenib (drug used in hematologic malignancies). Positive controls involved cell lines treated with staurosporine at different concentrations (staurosporine is a standard control compound for kinase inhibitors due to its high broad-spectrum potency in inhibiting most protein kinases at sub-micromolar concentrations).
The results were as follows:
- In CRC MSI-H, ASXL1 mutations were observed in 7/12 (
58% ) of PDCs, aligning with predicted frequency of ~55% - In NSCLC, ASXL1 mutations occurred in 2/6 (
33% ) studied cell lines, higher than predicted2.6% - Overall, in 18 studied solid cancer cell lines, ASXL1 mutations were recorded in 9 cell lines and no ASXL1 mutations were recorded in 9 cell lines which were designated as control
- In ASXL1 mutated cell lines, high SLS009 efficacy (IC50 <100 nM) was observed in 6/9 (
67% ) solid cancer cell lines and in non-ASXL1 mutated cancer high SLS009 efficacy was observed in 0/9 (0% ) of studied solid cancer cell lines- In CRC MSI-H, high efficacy (IC50 <100 nM) was observed in 4/7 (
57% ) of ASXL1 mutated cell lines and in 0/5 (0% ) of non-ASXL1 mutated cell lines - In NSCLC, high efficacy (IC50 <100 nM) was observed in 2/2 (
100% ) of ASXL1 mutated cell lines and in 0/4 (0% ) of non-ASXL1 mutated cell lines
- In CRC MSI-H, high efficacy (IC50 <100 nM) was observed in 4/7 (
- No activity was observed in any of the studied cell lines with revumenib (negative control) at any concentration
- Staurosporine activity was confirmed, but interestingly and importantly, SLS009 outperformed positive control staurosporine in 5/9 cell lines
“These findings are incredibly encouraging and validate our approach to developing a targeted solid tumor therapy. We are excited that our hypotheses were confirmed, marking, to the best of our knowledge, the first study to advance the identification of ASXL1 mutations as a potential biomarker for a drug response in solid cancers,” said Dr. Dragan Cicic, Senior Vice President, Chief Development Officer at SELLAS. “Our experiments show that SLS009 demonstrates high efficacy with low IC50 values and with
SELLAS has filed for provisional patent protection for the use of ASXL1 mutations as predictive diagnostic for selection of cancer patients likely to benefit based on clinical data and biology.
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 (formerly GFH009) - 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 28, 2024 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
SELLAS@lifesciadvisors.com
Media Contact
Michael Fitzhugh
LifeSci Communications
mfitzhugh@lifescicomms.com
FAQ
What is the efficacy rate of SLS009 in ASXL1 mutated solid cancers?
How effective is SLS009 in NSCLC with ASXL1 mutations?
What is the frequency of ASXL1 mutations in CRC MSI-H according to SELLAS study?
How does SLS009 compare to control treatments in the SELLAS study?
