Tango Therapeutics, Inc. · NASDAQ:TNGX
Tango Therapeutics — Investor Presentation (May 2025)
34 slides from Tango Therapeutics's investor presentation, May 2025
Slide 1: The next wave of targeted therapies in oncology
The next wave of targeted therapies in oncology Corporate Overview May 2025 | 1
Slide 2: Disclaimer and Safe Harbor Statement
Disclaimer and Safe Harbor Statement Certain statements in this presentation may be considered forward-looking statements. Forward-looking statements generally relate to future events, Tango’s future financial and operating performance, goals, expectations, beliefs, development plans, as well as dev
Slide 3: Company Overview
COMPANY OVERVIEW 2 TANGO
Slide 4: Significant opportunity to treat multiple common cancers
Significant opportunity to treat multiple common cancers Potential best-in-class oral PRMT5 inhibitors First-in-class oral CoREST inhibitor TNG462 TNG456 TNG260 • Key indications are lung and • Key indication is glioblastoma • Key indication is STK11-mut lung pancreatic cancer – 45% of GBM is MTAP-d
Slide 5: ~50K treatable MTAP-del patients/year (US)
~50K treatable MTAP-del patients/year (US) MTAP deletion % Number of cases NSCLC 15% Large unmet need Pancreatic 35% GBM/glioma 45% • MTAP deletion confers sensitivity Bladder 26% to PRMT5 inhibitors Breast 4% Melanoma 16% • Up to ~37K MTAP-del lung and pancreatic cancer patients/yr Esophageal 21% (
Slide 6: TNG462 and TNG456 selectively inhibit PRMT5 in MTAP-del cancers
TNG462 and TNG456 selectively inhibit PRMT5 in MTAP-del cancers Normal cells MTAP-del cancer cells Key points Me • TNG462 and TNG456 selectively kill MTAP-del SAM MTA cancer cells while sparing Client protein normal cells • TNG462 and TNG456 Active PRMT5 Inactive PRMT5 lock PRMT5-MTA into the inacti
Slide 7: MTAP-del cancers are uniquely sensitive to PRMT5 inhibition
MTAP-del cancers are uniquely sensitive to PRMT5 inhibition MTAP deletion occurs in 10-15% of cancers X X MTAP deletion causes MTA accumulation only in cancer cells SAM MTA MTA partially inhibits PRMT5 by replacing SAM SAM MTA MTA activates PRMT5 in normal cells PRMT5 TNG462 inhibit PRMT5 only in MT
Slide 8: Tango PRMT5 inhibitors have superior preclinical efficacy
Tango PRMT5 inhibitors have superior preclinical efficacy LU99 non-small cell lung cancer MTAP del, KRAS mut Tango PRMT5 inhibitors TNG462 TNG456 MRTX1719 AMG 193 MRTX1719 Engstrom et al., 2023 Belmontes et al., 2024 Deep tumor Deep tumor regression regression Tumor stasis Tumor growth inhibition |
Slide 9: A clinical pipeline targeting multiple high-value indications
A clinical pipeline targeting multiple high-value indications PATIENT TARGET MOLECULE INDICATIONS CLINICAL TRIALS STATUS SELECTION Pre-clinical Phase 1/2 Phase 3 Pancreatic, lung, MTAP-del other non-CNS Dose expansion ongoing cancers cancer TNG462 + RASi Pancreatic and PRMT5 (RevMed) lung cancer Enr
Slide 10: TNG462 PRMT5 inhibition in MTAP-del cancers
TNG462 PRMT5 inhibition in MTAP-del cancers | 10
Slide 11: TNG462 is a potentially best-in-class PRMT5 inhibitor
TNG462 is a potentially best-in-class PRMT5 inhibitor Durable clinical responses in late-line lung and pancreatic cancer • RECIST partial responses and durable disease control in multiple cancer types • 24 week mPFS in dose escalation cohort at active doses in late-line, difficult-to-treat cancers •
Slide 12: TNG462 dose expansion enrolling pancreatic and lung cancer
TNG462 dose expansion enrolling pancreatic and lung cancer DOSE EXPANSION PHASE 1/2 STUDY (ongoing) • Durable activity in multiple DOSE Non-small cell lung cancer types with excellent ESCALATION tolerability profile • Solid tumors with • Dose expansion ongoing at 250 MTAP deletion Pancreatic mg QD •
Slide 13: TNG462 demonstrates durable clinical activity and better tolerability
TNG462 phase 1 study demonstrates durable clinical activity and better tolerability than other PRMT5 programs Demonstrated best-in-class potential • RECIST partial responses in multiple tumor types, including lung and pancreatic cancer • Median time to RECIST response 16 weeks • 24 weeks mPFS in esc
Slide 14: TNG462 on-target cytopenias occur at predicted exposures
TNG462 on-target cytopenias occur at predicted exposures TNG462 exposure at clinically active doses 15 12 DLT Fold Over Free Cave Mouse Efficacy 600mg Predicted cytopenia threshold based Predicted dose limiting cytopenia 9 on GSK595 clinical data Cl 250mg 6 300mg Clinically active and well- 3 200mg
Slide 15: TNG462 activity in cholangiocarcinoma as a potential indicator
TNG462 activity in cholangiocarcinoma as a potential indicator of activity in lung and pancreatic cancer TNG462 ORR 43% Key points BOR • 3/7 RECIST PRs in evaluable -2% patients at active doses -36% • ORR compares favorably to other -49% treatment options -48% – TNG462 43% -42% Stable 0% disease – 2
Slide 16: TNG462 safety and tolerability profile is superior to competitors
TNG462 safety and tolerability profile is superior to competitors TNG462 BMS-504 AMG 193 200 mg* 200-600 mg 1200 mg TNG462 160/200 mg 0/30 dose reductions (0%) Dose reductions unknown 6/18 dose reductions (33%) No thrombocytopenia Frequent GI side effects Significant nausea, vomiting, Minimal nausea
Slide 17: TNG462 + RASi trial design
TNG462 + RASi trial design DOSE ESCALATION PHASE 1/2 STUDY TNG462 + • Potential to transform care in Any RAS mut daraxonrasib front line pancreatic cancer • Escalation starting at active MTAP-del dose ranges for all drugs pancreatic cancer and non-small cell • Enrollment planned 2Q 2025 lung cancer
Slide 18: TNG462 + RAS inhibition is very active in preclinical models
TNG462 + RAS inhibition is very active in preclinical models TNG462 + Zoldonrasib (RMC-9805) Key points KP4 MTAP-null, KRASG12D PDAC CDX • 40% of pancreatic cancers have a RAS G12D mutation • Clinical collaboration with Revolution Medicines to evaluate TNG462 + zoldonrasib (RAS G12D-selective inhibi
Slide 19: TNG456 PRMT5 inhibition in MTAP-deleted cancers
TNG456 PRMT5 inhibition in MTAP-deleted cancers | 19
Slide 20: TNG456 is a next-generation CNS-penetrant PRMT5 inhibitor
TNG456 is a next-generation CNS-penetrant PRMT5 inhibitor Superior preclinical profile to address high unmet need in glioblastoma • Enhanced potency and MTAP selectivity • Predicted brain exposure well above efficacy threshold • Key indication for development is MTAP-del glioblastoma (7,000 patients
Slide 21: TNG456 brain exposure predicted to be above clinical efficacy threshold
TNG456 brain exposure predicted to be above clinical efficacy threshold Predicted TNG456 exposure in plasma and brain 12 • TNG456 5X more potent and 3X more selective than TNG908 10 Fold Over Free Cave Mouse Efficacy • Predicted TNG456 brain exposure 8 2X above efficacy threshold Ne • Measured TNG90
Slide 22: TNG456 phase 1/2 clinical study
TNG456 phase 1/2 clinical study DOSE DOSE ESCALATION EXPANSION SUMMARY • 10% lung cancer patients have brain mets at diagnosis, up to GBM 40% will develop over time TNG456 • Abemiciclib combination to start with evidence of single Solid tumors with agent TNG456 activity in GBM MTAP deletion NSCLC |
Slide 23: PRMT5 program development plans
PRMT5 program development plans Potential best-in-class PRMT5 inhibitors for multiple common cancers TNG462 • Monotherapy enrollment focused on lung and pancreatic cancer at 250 mg QD • Combination with KRAS inhibitors enrollment 2Q 2025 • Registration trials in pancreatic and lung cancer planned 20
Slide 24: TNG260 CoREST inhibition in STK11-mutant cancers
TNG260 CoREST inhibition in STK11-mutant cancers | 24
Slide 25: STK11 mutant lung cancer responds poorly to standard of care
STK11 mutant lung cancer responds poorly to standard of care Overall survival in 1L lung cancer is significantly lower Summary in STK11 mut vs. WT patients • ~20% of non-small cell lung cancer is STK11 mut • STK11 included on all commercial NGS panels • Median OS 6.4 vs 12.7 mo for STK mut vs WT pat
Slide 26: TNG260 restores α-PD-1 responsiveness to STK11-mutant cancers
TNG260 restores α−PD-1 responsiveness to STK11-mutant cancers TNG260 restores α-PD1 efficacy Selective CoREST complex inhibition in syngeneic models MC38 STK11-mutant colon (engineered syngeneic) 3000 TNG260 Tumor volume (mm3) 2000 Tumor re-implantation 1000 HDAC1 complexes 0 0 10 20 70 80 90 Days A
Slide 27: TNG260 converts STK11-mut immune microenvironment to responsive
Clinical data demonstrateTNG260 converts STK11-mut immune microenvironment from unresponsive to responsive PD-L1 tumor score Intra-tumoral cytotoxic T cells Pre-treatment On treatment Pre-treatment On treatment 10% 75% Tumor cells Cytotoxic T cells Increased tumor cell surface PD-L1 Increased tumor
Slide 28: TNG260 + pembrolizumab in STK11-mutant non-small cell lung cancer
TNG260 + pembrolizumab in checkpoint inhibitor refractory STK11-mutant non-small cell lung cancer PHASE 1/2 STUDY DOSE DOSE EXPANSION • STK11 mutations associated with ESCALATION checkpoint inhibitor resistance in (ongoing) NSCLC Solid tumors with STK11 mut • 20% NSCLC is STK11-mut STK11 mutation NS
Slide 29: TNG961 HBS1L degrader for FOCAD-del cancers
TNG961 HBS1L degrader for FOCAD-del cancers | 29
Slide 30: FOCAD deletion occurs in 20-40% of MTAP-del cancers
FOCAD deletion occurs in 20-40% of MTAP-del cancers HBS1L degradation and FOCAD deletion TNG961 is a potential first-in-class are synthetic lethal HBS1L degrader • ~7% non small cell lung cancer HBS1L is FOCAD-del PELO • FOCAD deletion accurately Release detected by IHC ribosome • All FOCAD-del canc
Slide 31: TNG961 drives tumor regression in FOCAD-del preclinical models
TNG961 drives tumor regression in FOCAD-del preclinical models Strong xenograft activity across lineages TNG961 NCI-H838 MIAPACA2 • Potent and selective HBS1L NSCLC PDAC degrader 2500 1500 • IC50 110 nM Tumor volume (mm3) Tumor volume (mm3) 2000 • 100X selectivity for FOCAD del vs 1000 1500 WT cells
Slide 32: Financial Highlights and Milestones
FINANCIAL HIGHLIGHTS AND MILESTONES | 32
Slide 33: Multiple projected key milestones and strong balance sheet
Multiple projected key milestones and strong balance sheet Clinical milestones Cash balance TNG456 phase 1/2 trial enrollment 2Q 2025 • $217M cash, cash equivalents and marketable securities as of March 2025 TNG462 clinical data update 2H 2025 • Cash runway 1Q 2027 TNG462 + daraxonrasib and TN
Slide 34: Tango Therapeutics
Ai; TANGO therapeutics
Tango Therapeutics — Investor Presentation (May 2025) on 6ix