Tango Therapeutics, Inc.

Item 7.01. Regulation FD Disclosure. On October 23, 2026, Tango Therapeutics, Inc. (the “Company”) issued a press release announcing updated results from the Company’s ongoing Phase 1/2 clinical trial evaluating vopimetostat in combination with RAS(ON) inhibitors from Revolution Medicines, Inc. A copy of the press release is attached as Exhibit 99.1 to this Current Report on Form 8-K and incorporated herein by reference. A copy of the presentation relating to the updated results from the Phase 1/2 trial is attached as Exhibit 99.2 to this Current Report on Form 8-K and incorporated herein by reference. The information in this Item 7.01, including Exhibits 99.1 and 99.2 of this Current Report on Form 8-K, are furnished and shall not be deemed to be “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section. The information in this Item 7.01 and Exhibits 99.1 and 99.2 of this Current Report on Form 8-K shall not be incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date of this Current Report on Form 8-K, regardless of any general incorporation language in any such filing.

Item 8.01. Other Events. Promising Results from Phase 1/2 Clinical Trial of Vopimetostat in Combination with RAS(ON) Inhibitors On October 23, 2026, the Company disclosed promising results from its ongoing Phase 1/2 trial evaluating vopimetostat in combination with RAS(ON) inhibitors from Revolution Medicines, Inc. in patients with MTAP-deleted and RAS-mutant metastatic pancreatic ductal adenocarcinoma (“PDAC”) and non-small cell lung cancer (“NSCLC”). As of the data cutoff date of August 20, 2026, updated data from the ongoing Phase 1/2 study demonstrated an 82% objective response rate (“ORR”), median progression-free survival (“PFS”) not yet reached, and a 9-month PFS rate of 88% in 22 patients with second line or third line MTAP-deleted/RAS-mutant PDAC who were efficacy-evaluable. The combination was generally well-tolerated in the 30 PDAC and NSCLC patients who received dose level 1. Vopimetostat plus Daraxonrasib As of the data cutoff date of August 20, 2026, 34 patients with previously treated MTAP-deleted and RAS-mutant PDAC (n=29) or NSCLC (n=5) were treated with vopimetostat plus daraxonrasib. The majority of PDAC patients (13 of 22 patients) who were efficacy-evaluable received the combination as third-line treatment. Efficacy-evaluable patients are those patients who received their first dose of treatment at least 14 weeks prior to the data cutoff date. In the vopimetostat plus daraxonrasib dose escalation arm, efficacy-evaluable patients received either vopimetostat 200 mg (n=19; dose level 1) or 250 mg (n=3; dose level 2) once daily (“QD”) plus daraxonrasib 100 mg QD. As of the data cutoff date of August 20, 2026, 22 patients were efficacy-evaluable, with median follow up of 7.1 months (range: 3.3-12.5 months). In efficacy-evaluable PDAC patients with MTAP-deleted, RAS-mutant PDAC, the Company observed an ORR of 82% (18 of 22 patients, with 11 of 18 confirmed partial responses (“cPRs”) and 7 unconfirmed partial responses with all unconfirmed responses confirmed after the data cutoff date). Median PFS has not yet been reached. The Company also observed an 88% 9-month PFS rate and a 100% disease control rate (“DCR”). Dose level 1 (n=25 safety-evaluable patients) of the vopimetostat plus daraxonrasib combination in PDAC patients was generally well-tolerated as of the data cutoff date. There were no dose-limiting toxicities (“DLTs”) and no withdrawals due to treatment-related adverse events (“TRAEs”). There were no Grade 4 or 5 TRAEs and the rate of Grade 3 TRAEs was 40% (10 of 25 patients). The most common TRAEs were Grade 1 or 2 stomatitis (48%), rash (44%), and diarrhea (28%). Dose level 2 (n=4 safety-evaluable patients) of the vopimetostat plus daraxonrasib combination in PDAC patients was not well-tolerated and there were 3 DLTs in 2 patients at this dose level. Safety evaluable patients are those who received at least one dose of the applicable combination prior to the data cutoff date. In NSCLC patients, the Company observed an ORR of 80% (4 of 5 patients, all of whom had cPRs) at dose level 1 and a 100% DCR. The vopimetostat plus daraxonrasib combination in NSCLC patients (n=5 safety-evaluable patients) had no Grade 4 or 5 TRAEs and the rate of Grade 3 TRAEs was 20% (1 of 5 patients). The most common TRAEs in NSCLC safety-evaluable patients were Grade 1 or 2 rash (100%), diarrhea (80%), stomatitis (40%), nausea (40%), and fatigue (40%). Vopimetostat plus Zoldonrasib In the vopimetostat plus zoldonrasib dose escalation arm, PDAC patients with MTAP deletion and KRAS G12D mutation received vopimetostat 200 mg or 250 mg QD plus zoldonrasib 600 mg or 1200 mg QD across four dose levels (dose level 1: 200 mg/600 mg QD; dose level 2: 250 mg/600 mg QD; dose level 3: 250 mg/1200 mg QD; and dose level 4: 200 mg/1200 mg QD). As of the data cutoff date of August 20, 2026, 35 patients were efficacy-evaluable, meaning that they received their first dose of treatment at least 14 weeks prior to the data cutoff date. 39 patients were safety-evaluable, meaning they received at least one dose of this combination prior to the data cutoff date. The Company observed an ORR of 54% (19 of 35 patients, with 18 cPRs and one confirmed complete response as of the data cutoff date) across all dose levels in the zoldonrasib plus vopimetostat arm. The Company also observed a 61% 9-month PFS rate and a 97% DCR in these patients. The vopimetostat plus zoldonrasib combination was generally well-tolerated across dose levels. There were no DLTs and no withdrawals due to TRAEs. The rate of dose reduction was 15% (6 of 39 patients). There were no Grade 5 TRAEs and there was one Grade 4 TRAE (3%). The rate of Grade 3 TRAEs was 28% (11/39 patients). The most common TRAEs were Grade 1 or 2 nausea (39%), vomiting (39%), dysgeusia (28%), and fatigue (26%). Regulatory Update Following recent interactions with the U.S. Food and Drug Administration (“FDA”), the Company plans to initiate a global, randomized registrational trial evaluating the combination of vopimetostat with daraxonrasib in front-line patients with MTAP-deleted PDAC. The planned study will randomize patients 1:1 to receive either vopimetostat (200 mg once daily) plus daraxonrasib (100 mg once daily) or standard-of-care chemotherapy. The dual primary endpoints of the planned study are ORR and PFS, with overall survival as a key secondary endpoint. The Company anticipates initiating this study in the first half of 2027. The Company is pursuing multiple pathways to obtain clinical supply of daraxonrasib for the planned study. In addition, the Company intends to discuss the possibility of seeking approval of this combination in patients with second line PDAC with regulatory authorities. Clinical Update The Company now expects to report data from its Phase 1/2 clinical trial of vopimetostat monotherapy in a cohort of patients with NSCLC in January 2027 and data from its Phase 1/2 clinical trial evaluating TNG456 as a monotherapy in NSCLC, glioblastoma, and other cancers in January 2027. Strategic Reprioritization On October 22, 2026, the Board of Directors of the Company approved a strategic reprioritization of the Company’s research and development activities to focus its efforts on the advancement of PRMT5-targeted therapies and the Company’s clinical product candidates, vopimetostat and TNG456, and to deprioritize novel target discovery (the “Plan”). In connection with the Plan, the Company intends to stop certain preclinical and research activities to focus on translational work and its PRMT5 programs, including a planned Phase 1/2 vopimetostat + RAS combination study in second line MTAP-wild type PDAC, which the Company plans to initiate in the first half of 2027. As part of the Plan, the Company intends to reduce its overall workforce by approximately 14%, with the majority of the headcount reductions from the Company’s research group.