TNG260 / Tango Therap - LARVOL DELTA

TNG260, a novel small-molecule CoREST inhibitor, sensitizes STK11-mutant tumors to anti-PD-1 therapy (SITC 2025) - P1/2 | "Through this mechanism, TNG260 sensitizes immunotherapy-resistant mouse models to anti-PD-1 treatment, illustrating a potential treatment strategy for patients with STK11-mutated tumors. TNG260 in combination with pembrolizumab is currently being evaluated in patients with STK11-mutated, advanced solid tumors (NCT05887492)."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • KRAS • STK11

A Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TNG260 in combination with pembrolizumab in patients with STK11-mutated advanced solid tumors (SITC 2025) - P1/2 | "Dose expansion is ongoing at the RP2D of 80 mg TNG260 plus standard dose pembrolizumab for patients with advanced KRAS wild-type/STK11 mutant NSCLC.Trial Registration NCT05887492Ethics Approval The study protocol was approved by the appropriate institutional review board at each participating site. All study subjects provided written informed consent prior to their participation in the trial."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • STK11

TNG260 Clinical Update (The Manila Times) - "Forty-one patients with STK11-mutant, locally advanced or metastatic solid tumors were enrolled, and 21/41 patients were evaluable at active doses. The maximum tolerated dose (MTD) was 80 mg QD...In this group (n=5), the mPFS was 27 weeks, more than double the standard of care PFS of ~10 weeks. There was no evidence of activity in other STK11 mutant cancers. Dose expansion is ongoing In the STK11mut/RAS WT lung cancer cohort...Details of this trial will be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting on November 7, 2025."

P1/2 data • Non Small Cell Lung Cancer • Solid Tumor

Precision Epigenetic Reprogramming: CoREST Inhibition Sensitizes STK11-Mutant Tumors to Immune Checkpoint Blockade Therapy. (PubMed, Cancer Res) - P1/2 | "Early clinical data from an ongoing trial (NCT05887492) show increased histone acetylation and CD8+ T-cell infiltration in patient tumors treated with TNG260 and pembrolizumab. We also outline key questions for future investigation, including durability of immune response, tumor-type specificity, and biomarker strategies for patient selection and response monitoring. See related article by Ahronian et al., p. 3966."

Checkpoint inhibition • IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • HDAC1 • STK11

Tango Therapeutics…announced that the company will have three poster presentations at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2025, including the first clinical data on the novel CoREST inhibitor TNG260 in non-small cell lung cancer (GlobeNewswire)

Clinical data • Non Small Cell Lung Cancer

TNG260 is a Small-Molecule CoREST Inhibitor that Sensitizes STK11-Mutant Tumors to Anti-PD-1 Immunotherapy. (PubMed, Cancer Res) - P1/2 | "In the tumors of patients with STK11-deficient cancers on a clinical trial (NCT05887492), treatment with a combination of TNG260 and pembrolizumab increased intratumoral histone acetylation, PD-L1 tumor proportion scores, and T cell infiltration into the tumor microenvironment. This study illustrates a promising treatment strategy for addressing immune evasion in STK11-mutant NSCLC patients."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HDAC1 • PD-L1 • STK11

Enantioselective Assembly of (Hetero)aryl Alkyl Sulfilimines via Copper-Catalyzed S-Arylation of S-Alkyl Sulfenamides with (Hetero)aryl Iodides. (PubMed, J Am Chem Soc) - "A wide range of functionalized (hetero)aryl iodides and S-alkyl sulfenamides are compatible under the reaction conditions, providing an attractive approach for assembling enantioenriched aryl alkyl sulfilimines. The utility of this method is demonstrated by the gram-scale asymmetric synthesis of clinical candidate TNG 260 and the formal asymmetric synthesis of three additional drug candidates."

Journal

Tango Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Highlights (GlobeNewswire) - "TNG260: The dose expansion cohort of the TNG260 Phase 1/2 trial is ongoing in NSCLC. The study is evaluating the pharmacokinetics, pharmacodynamics, safety and efficacy of TNG260 in combination with pembrolizumab in patients with an STK11 loss-of-function mutation. The Company plans to provide a clinical update on TNG260 in the second half of 2025."

P1/2 data • Trial status • Non Small Cell Lung Cancer

Tango Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Highlights (GlobeNewswire) - "Upcoming Milestones: TNG456 phase 1/2 trial enrollment expected to begin 1H 2025; TNG260 clinical data update expected in 2025."

P1/2 data • Trial status • Oncology • Solid Tumor

Study of TNG260 and an Anti-PD Antibody in STK11 Mutated Solid Tumors (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: Tango Therapeutics, Inc. | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jan 2025 ➔ Jan 2026

IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Endometrial Cancer • Hepatology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • STK11

Tango Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Highlights (Businesswire) - "TNG456 is a next-generation brain-penetrant MTA-cooperative PRMT5 inhibitor that is 55X selective for MTAP deletion with 20 nM potency....The Company expects to begin enrolling patients in the planned phase 1/2 trial during 1H 2025....The TNG260 phase 1/2 clinical trial is ongoing, evaluating safety, pharmacokinetics, pharmacodynamics and efficacy of TNG260 in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors with an STK11 loss-of-function mutation....TNG260 clinical data expected in 2025."

New P1 trial • P1/2 data • Breast Cancer • Cervical Cancer • Endometrial Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

Experimental 'loss-of function' annotation of STK11 mutations with prognostic and therapeutic implications (TNG260mutationfinder.com) (AACR 2024) - P1/2 | "Though STK11 is commonly inactivated in human cancer with strong implications for treatment outcomes, few STK11 mutations identified from tumor samples have been functionally characterized.TNG260 is an inhibitor of CoREST that is currently being investigated in combination with pembrolizumab for the treatment of STK11-mutant cancer (NCT05887492). This library was expressed in A549, and cells were maintained in vitro or in vivo to allow for positive selection of STK11 loss-of-function variants and depletion of variants that behave like wild-type STK11. At the end of the screen, variants were quantified by NGS using each mutant cDNA's unique barcode and compared to well-annotated controls.These data were assembled to generate TNG260mutationfinder.com -- the first website to curate STK11 variants with functional annotations."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • STK11

TNG260, a small molecule CoREST inhibitor, sensitizes STK11-mutant NSCLC to anti-PD1 immunotherapy (AACR 2024) - P1/2 | "In vivo CRISPR screens in tumor-bearing immune competent mice identified the Corepressor of Repressor Element 1 Silencing Transcription (CoREST) complex as a synthetic lethal immune evasion target for STK11- mutant tumors. This work identifies new vulnerabilities in STK11 LOF cancers that can be exploited therapeutically. TNG260 is currently being investigated in combination with pembrolizumab for the treatment of STK11-mutant cancer (NCT05887492), including NSCLC."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDK7 • KRAS • STK11 • TP53

Tango Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Highlights (Businesswire) - "Upcoming Milestones: Clinical data from the ongoing TNG908 phase 1/2 trial are expected in 2024....In March 2024, an oral presentation of the discovery and preclinical characterization of TNG348 will be presented at the ACS Spring Meeting, supporting the further development and ongoing phase 1/2 clinical trial of TNG348 as a single agent and in combination with olaparib....In April 2024, seven posters will be presented highlighting preclinical data from the Company’s clinical-stage precision oncology pipeline and synthetic lethality discovery platform. Ayushi Patel, Ph.D. from NYU Langone Health will present a minisymposium based on a Tango-NYU collaboration to study TNG260 in STK11 mutant non-small cell lung cancer in preclinical models."

P1/2 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Tango Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Highlights (Businesswire) - "Dose escalation is ongoing in the TNG260 phase 1/2 clinical trial evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of TNG260 in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors with an STK11 loss-of-function mutation. To date, the preliminary safety, tolerability and pharmacokinetics profiles are favorable....Dose escalation is ongoing in the TNG348 phase 1/2 clinical trial evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of TNG348 as a single agent and in combination with olaparib, a PARP inhibitor, in patients with BRCA1/2-mutant and other HRD+ (homologous recombination deficient) cancers."

Trial status • Oncology • Solid Tumor

Tango Therapeutics to Highlight Preclinical Data on Precision Oncology Pipeline at the American Association for Cancer Research (AACR) Annual Meeting 2024 (GlobeNewswire) - "Tango Therapeutics, Inc...today announced that one abstract has been selected for an oral minisymposium and seven abstracts have been accepted as poster presentations at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place April 5-10, 2024, in San Diego, California."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

CoREST inhibition by TNG260 increases expression of immunomodulatory genes in STK11-mutant cancer and sensitizes to immune checkpoint blockade (SITC 2023) - "Background Loss of function mutations in STK11 drive immune evasion and cause resistance to immune checkpoint blockade...Similarly, the AXL inhibitor, bemcentinib, provided a minor enhancement to the tumor growth inhibition seen with anti-PD1 as a single agent in this model...Unlike other small molecules being combined with anti-PD1 for STK11-deficient NSCLC, the combination of TNG260 with anti-PD1 drives tumor regressions in STK11-deficient models that are typically resistant to anti-PD1 monotherapy. TNG260 is under investigation in a Phase 1/2 study as a single agent and in combination with pembrolizumab for patients with STK11-mutated, advanced solid tumors."

Checkpoint block • Checkpoint inhibition • Immunomodulating • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IFNG • STK11

Tango Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Highlights (GlobeNewswire) - "Upcoming Milestones: TNG348 phase 1/2 clinical trial initiation expected 1H 2024. Additional data from the ongoing TNG908 clinical trial expected 2024....Society for NeuroOncology (SNO) 28th Annual Meeting, November 15-19, 2023, Vancouver, Canada: In November 2023, preclinical data will be presented in two poster presentations supporting the development of PRMT5 inhibitors in MTAP-deleted glioblastoma and malignant peripheral nerve sheath tumors....In November 2023, Tango scientists presented preclinical data highlighting the potential of TNG260 in STK11-mutant cancers. Preclinically, TNG260 combined with anti-PD1 therapy drives tumor regression in STK11-deficient models that are resistant to anti-PD1 monotherapy."

P1/2 data • Preclinical • Trial status • Breast Cancer • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

Tango Therapeutics Announces First Patient Dosed in TNG260 Phase 1/2 Trial in Patients With STK11-Mutant Cancers (GlobeNewswire) - "Tango Therapeutics, Inc...announced that the first patient has been dosed in the phase 1/2 trial evaluating TNG260 in combination with pembrolizumab in patients with STK11-mutant cancers....The phase 1/2 trial will evaluate the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of TNG260, with a one cycle single agent run-in phase to evaluate the safety and PK of TNG260, in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors with an STK11 loss-of-function mutation."

Trial status • Endometrial Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Study of TNG260 and an Anti-PD Antibody in STK11 Mutated Solid Tumors (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: Tango Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • IO biomarker • Metastases • Breast Cancer • Cervical Cancer • Endometrial Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • STK11

Study of TNG260 and an Anti-PD Antibody in STK11 Mutated Solid Tumors (clinicaltrials.gov) - P1/2 | N=126 | Not yet recruiting | Sponsor: Tango Therapeutics, Inc.

Combination therapy • IO biomarker • Metastases • New P1/2 trial • Breast Cancer • Cervical Cancer • Endometrial Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • STK11

Tango Therapeutics Reports First Quarter 2023 Financial Results and Provides Business Highlights (GlobeNewswire) - "Upcoming Milestones: First patient dose in the TNG462 phase 1/2 clinical trial expected mid-2023. TNG348 IND filing expected mid-2023. TNG260 phase 1/2 clinical trial initiation expected 2H 2023. Additional data from the ongoing TNG908 clinical trial expected 2024."

IND • New P1/2 trial • P1/2 data • Trial status • Brain Cancer • CNS Tumor • Oncology • Solid Tumor

TNG260: A novel, orally active, CoREST-selective deacetylase inhibitor for the treatment of STK11-mutant cancers (AACR 2023) - "Unlike previously developed pan-HDAC inhibitors, which are directly cytotoxic to cancer (and immune) cells, IND-enabling toxicology studies in rat and dog showed that TNG260 was well-tolerated at exposures predicted to be efficacious in humans, with bone marrow suppression only detectable at doses where TNG260 is no longer selective for CoREST inhibition. TNG260 clinical development will be among the first to combine the power of genetic patient selection and immunotherapy, evaluating patients with STK11 mutant cancers in a trial combining TNG260 and a checkpoint inhibitor."

IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HDAC1 • HDAC3 • STK11

Tango Therapeutics Presents Preclinical Data on Precision Oncology Programs at the American Association of Cancer Research 2023 Annual Meeting (GlobeNewswire) - "Tango Therapeutics...announced highlights from presentations at the American Association for Cancer Research (AACR) 2023 Annual Meeting, taking place from April 14-19, 2023....TNG908 is brain penetrant and is efficacious in both subcutaneous and orthotopic MTAP-null glioblastoma xenograft models....TNG260 in combination with an anti-PD1 antibody drives strong anti-tumor efficacy in STK11-null checkpoint inhibitor resistant mouse models. A phase 1/2 clinical trial of TNG260 and pembrolizumab in patients with STK11 mutant cancers is expected to start in the second half of 2023."

New P1/2 trial • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • STK11

Tango Therapeutics Announces FDA Clearance of Investigational New Drug Application for TNG260, a First-in-Class CoREST Inhibitor for the Treatment of STK11-Mutant Cancers (GlobeNewswire) - "Tango Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for TNG260, a first-in-class inhibitor of the CoREST complex (Co-repressor of Repressor Element-1 Silencing Transcription), for the treatment of STK11-mutant cancers....'We expect that TNG260 will be among the first oncology molecules to leverage the benefits of genetically-based patient selection (STK11-mutation) with checkpoint inhibitor therapy. We look forward to initiating the Phase 1/2 clinical trial of TNG260 in the second half of 2023'."

IND • Oncology