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    STX-721

    i
    Other names: STX-721, PFL-721, PFL721, PFL 721, STX721, STX 721, ST5924, ST 5924, ST-5924
    Associations

    News

    Trials
    Company:
    Antares Therapeutics, Pierre Fabre
    Drug class:
    Associations

    News

    Trials
    6ms
    STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models. (PubMed, Clin Cancer Res)
    In carefully benchmarked biochemical, biophysical, and cellular assays, STX-721 demonstrated superior ex20ins-mutant selectivity relative to other tested benchmark clinical phase compounds and achieved ex20ins-mutant-selective tumor regression in vivo. These data highlight that STX-721 shows a high level of mutant EGFR selectivity across human preclinical cancer models and may provide an improved clinical efficacy versus adverse event profile relative to existing drugs.
    Preclinical • Journal
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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    EGFR mutation • EGFR exon 20 insertion • EGFR wild-type • EGFR exon 20 mutation
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    STX-721
    8ms
    First-In-Human Study of STX-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations (clinicaltrials.gov)
    P1/2, N=185, Recruiting, Antares Therapeutics, Inc | N=120 --> 185
    Enrollment change
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    EGFR (Epidermal growth factor receptor)
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    EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
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    STX-721
    11ms
    Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer. (PubMed, J Med Chem)
    STX-721 (53) is a potent, irreversible inhibitor of the majority of EGFR/HER2 ex20ins mutants and demonstrates excellent mutant vs wild-type selectivity both in vitro and in vivo. STX-721 is currently in phase 1/2 clinical trials for EGFR/HER2 ex20ins-driven NSCLC.
    Journal
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR wild-type • HER-2 exon 20 insertion
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    STX-721
    2years
    First-In-Human Study of STX-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations (clinicaltrials.gov)
    P1/2, N=120, Recruiting, Scorpion Therapeutics, Inc. | Not yet recruiting --> Recruiting | Trial primary completion date: Jul 2026 --> Jun 2027
    Enrollment open • Trial primary completion date • EGFR exon 20 • HER2 exon 20 • Metastases
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    EGFR (Epidermal growth factor receptor)
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    EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    STX-721
    2years
    First-In-Human Study of STX-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations (clinicaltrials.gov)
    P1/2, N=120, Not yet recruiting, Scorpion Therapeutics, Inc.
    New P1/2 trial • EGFR exon 20 • HER2 exon 20 • Metastases
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    EGFR (Epidermal growth factor receptor)
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    EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
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    STX-721
    over2years
    Discovery of STX-721, a potent and Mutant-Selective EGFR exon 20 inhibitor with a potential best-in-class profile (ACS-Fall 2023)
    Approved and investigational therapies for NSCLC patients with EGFR exon 20 insertion mutations have only demonstrated moderate clinical efficacy (28-52% ORR), compared to Osimertinib's significant 70-80% ORR activity in the more common EGFR mutant tumors. Here we disclose for the first time the structure and optimization efforts that led to the discovery of STX-721, a highly-differentiated EGFR/HER2 inhibitor that provides superior exon 20 insertion mutation vs. wild type selectivity relative to approved and clinical benchmarks across in vitro and in vivo model biological systems, including in vivo isogenic/matched human cancer cell line models. STX-721 has the potential to provide a best-in-class profile to improve outcomes in patients harboring cancers with EGFR/HER2 exon 20 mutations and has completed investigational new drug (IND)-enabling studies with a favorable risk/benefit profile supporting clinical development.
    EGFR exon 20
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    EGFR mutation • EGFR exon 20 insertion • EGFR wild-type • EGFR exon 20 mutation • HER-2 exon 23 mutation
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    Tagrisso (osimertinib) • STX-721
    over3years
    Identification of STX-721, an EGFR exon 20 mutant inhibitor with superior selectivity and a potential best-in-class profile (AACR-NCI-EORTC 2022)
    STX-721 demonstrates EGFR exon 20 mutant selectivity approaching the selectivity of Osimertinib in EGFR T790M mutants, warranting further exploration of this potential best-in-class exon 20 inhibitor in the clinic. Ba/F3: proliferation selectivity vs. EGFR WT Human cells: proliferation selectivity (vs.
    EGFR exon 20
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    EGFR (Epidermal growth factor receptor)
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    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR wild-type • EGFR exon 20 mutation • EGFR H1975
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    Tagrisso (osimertinib) • Pozenveo (poziotinib) • Exkivity (mobocertinib) • tuxobertinib (BDTX-189) • Zegfrovy (sunvozertinib) • zipalertinib (CLN-081) • STX-721