Tango Therapeutics, Inc. · NASDAQ:TNGX
Tango Therapeutics — Investor Presentation (January 2025)
40 slides from Tango Therapeutics's investor presentation, Jan 13, 2025
Slide 1: The next wave of targeted therapies in oncology
Exhibit 99.1 The next wave of targeted therapies in oncology Corporate Overview January 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 TNG260 TNG462 TNG456 • Key indications are lung and • Key indication is glioblastoma • Key indication is STK11-mut lung pancreatic cancer cancer – 45% of
Slide 5: ~50K total treatable MTAP-deleted patients/year (US)
~50K total treatable MTAP-deleted patients/year (US) MTAP Number of cases deletion % Large unmet need NSCLC 15% Pancreatic 22%-35% ~15K GBM/glioma 46% • MTAP deletion confers sensitivity Bladder 26% to PRMT5 inhibitors Breast 4% • Up to ~37K MTAP-del lung and Melanoma 16% pancreatic cancer patients/
Slide 6: TNG462 and TNG456 selectively inhibit PRMT5 in MTAP-deleted cancers
TNG462 and TNG456 selectively inhibit PRMT5 in MTAP-deleted cancers Normal cells MTAP-del cancer cells Key points Me • TNG462 and TNG456 selectively kill MTAP-del SAM MTA cancer cells while sparing Client normal cells protein • TNG462 and TNG456 Active PRMT5 Inactive PRMT5 lock PRMT5-MTA into the in
Slide 7: MTAP-del cancers are uniquely sensitive to PRMT5 inhibition
SAM MTAP-del cancers are uniquely sensitive to PRMT5 inhibition MTAP deletion occurs in 10-15% of cancers X MTAP deletion causes MTA accumulation only in cancer cells X MTA partially inhibits PRMT5 by replacing SAM MTA SAM MTA MTA activates PRMT5 in normal cells TNG462 inhibit PRMT5 only in MTAP-del
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 Tumor stasis Tumor growth inhibition regression regression |
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 Pancreatic and + RASi Enrollment 1H2025 lung cancer TNG462
Slide 10: TNG462: PRMT5 inhibition in MTAP-deleted cancers
TNG462 PRMT5 inhibition in MTAP-deleted 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 PRs and durable disease control in multiple cancers • 24 weeks mPFS in dose escalation cohort of late-line, difficult-to-treat cancers (active doses) • Excellent safety a
Slide 12: TNG462 dose expansion enrolling in multiple histologies
TNG462 dose expansion enrolling in multiple histologies PHASE 1/2 STUDY DOSE EXPANSION (ongoing) • Durable activity in multiple cancer types with excellent Non-small cell lung DOSE tolerability profile ESCALATION • Dose expansion ongoing at 250 Pancreatic mg QD • Solid tumors with MTAP deletion • Fi
Slide 13: TNG462 phase 1/2 study demonstrates durable clinical activity
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 NSCLC and pancreatic cancer* • Median time to RECIST response 16 weeks • 24 weeks mPFS in e
Slide 14: TNG462 on-target cytopenias occur at predicted exposures
TNG462 on-target cytopenias occur at predicted exposures Efficacious TNG462 exposure at clinically active doses 15 Dose limiting cytopenias 600 12 mg observed Predicted cytopenia threshold based 9 on GSK595 clinical data Cl 300 mg 6 Clinically active and well- tolerated 3 Clinical efficacy threshold
Slide 15: TNG462 activity in cholangiocarcinoma
TNG462 activity in cholangiocarcinoma as a potential indicator of activity in lung and pancreatic cancer TNG462 ORR 43% Key points • 3/7 evaluable patients treated at BOR active doses with RECIST PRs -2%‒ TNG462 43% -36% ‒ BMS-504 18% (2/11) -49% ‒ AMG 193 15% (2/13) -48% -42% Stable disease • Compa
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 6/18 dose reductions (33%) 0/30 dose reductions (0%) Dose reductions unknown Significant nausea, vomiting, No thrombocytopenia Frequent GI side effects decreased appe
Slide 17: TNG462 combinations enable use in first line indications
TNG462 combinations enable use in first line indications Multiple combinations to start 2025 First line standard of care combinations • Pembrolizumab in lung cancer • FOLFIRINOX in pancreatic cancer • Gemcitabine/abraxane in pancreatic cancer • Carboplatin/pemetrexed in lung cancer (adeno) • Carbopl
Slide 18: TNG462 + KRAS inhibition is very active in preclinical models
TNG462 + KRAS inhibition is very active in preclinical models TNG462 + RMC-9805 TNG462 monotherapy KP4 KP4 G12D G12D MTAP-null, KRAS PDAC CDX MTAP-null, KRAS PDAC CDX *TNG462 exposure in combination formulation predicted equivalent to 30 mpk monotherapy • 40% of pancreatic cancers have a KRAS G12D d
Slide 19: TNG908: Clinically active CNS-penetrant PRMT5 inhibitor replaced by TNG456
TNG908 Clinically active CNS-penetrant PRMT5 inhibitor replaced by next-gen molecule TNG456 | 19
Slide 20: TNG908 is a clinically active PRMT5 inhibitor
TNG908 is a clinically active PRMT5 inhibitor Discontinued in favor of TNG462 and TNG456 (CNS) • Effective in multiple cancers including lung and pancreatic cancers • 16 weeks mPFS in dose escalation cohort of late-line, difficult-to-treat cancers • No evidence of activity in glioblastoma, CNS expos
Slide 21: TNG908 is active and well-tolerated in non-CNS solid tumors
TNG908 is active and well-tolerated in non-CNS solid tumors All patients • TNG908 dose escalation began August 2022, dose expansion began April 2024 • 110 patients enrolled All non-CNS solid tumors • 77 patients enrolled, 39 evaluable at active doses (24 histologies) • 8 partial responses observed (
Slide 22: TNG908 is active across histologies
TNG908 is active across histologies TNG908 400-900 mg QD Histology-specific activity (n=41) Pancreatic cancer (36% ORR) • n=14, 11 evaluable • 4 PR (3 ongoing) • 3 SD (1 ongoing) NSCLC (11% ORR) • n=12, 9 evaluable • 1 PR (ongoing) * * * * • 7 SD (3 ongoing, 2 near PR) * Confirmed partial response S
Slide 23: TNG908 is clinically active, TNG462 has the potential to be best-in-class
TNG908 is clinically active, TNG462 has the potential to be best-in- class TNG462 • TNG462 target coverage is 2-4X better than TNG908 • TNG462 median time on treatment of 24 weeks is notably longer than TNG908 (16 weeks) • TNG462 tolerability profile is superior to TNG908 with less nausea, vomiting
Slide 24: TNG456: PRMT5 inhibition in MTAP-deleted cancers
TNG456 PRMT5 inhibition in MTAP-deleted cancers | 24
Slide 25: TNG456 is a next-generation CNS-penetrant PRMT5 inhibitor
TNG456 is a next-generation CNS-penetrant PRMT5 inhibitor Replaced TNG908 for CNS cancers • Enhanced potency and MTAP selectivity • Predicted CNS exposure well above efficacy threshold • Key indication for development - MTAP-deleted glioblastoma (7,000 patients/yr US) • First patient dose planned 1H
Slide 26: TNG456 is active as monotherapy and with CDK4/6i in glioblastoma xenograft
TNG456 is active as monotherapy and in combination with CDK4/6i in a glioblastoma xenograft TNG456 + abemaciclib Summary TNG456 monotherapy drives additional survival benefit U87MG U87MG • TNG456 preclinical Kpuu (MTAP-null GBM CDX) (MTAP-null GBM CDX) 0.5-1.1 in NHP CSF and dog brain • TNG456 + abe
Slide 27: TNG456 CSF exposure predicted to be above clinical efficacy threshold
TNG456 CSF exposure predicted to be above clinical efficacy threshold Steady-state clinical exposure in plasma and CSF 4 • TNG456 is 5X more potent and 3X more selective than TNG908 • TNG908 CSF exposure 0.3X plasma 3 • TNG456 CSF exposure predicted to be 2X efficacy threshold at 0.3X Ne plasma expo
Slide 28: TNG456 phase 1/2 clinical study
TNG456 phase 1/2 clinical study DOSE DOSE SUMMARY EXPANSION ESCALATION • Safety, PK/PD and efficacy GBM TNG456 as primary endpoints Solid tumors with • Combination with NSCLC MTAP deletion abemaciclib to start at pharmacologically active TNG456 dose GBM • Enrollment planned 1H 2025 TNG456 + NSCLC ab
Slide 29: PRMT5 program development plans
PRMT5 program development plans Potential best-in-class PRMT5 inhibitors for multiple common cancers TNG908 • Active and well-tolerated • Development discontinued in favor of TNG462 (non-CNS cancers) and TNG456 (glioblastoma) TNG462 • Monotherapy expansion cohorts focused on lung and pancreatic canc
Slide 30: TNG260: CoREST inhibition in STK11-mutant cancers
TNG260 CoREST inhibition in STK11-mutant cancers | 30
Slide 31: TNG260 reverses immune evasion caused by STK11 mutations
TNG260 reverses immune evasion caused by STK11 mutations Immune evasion driven by TNG260 reverses tumor-intrinsic immune evasion tumor suppressor gene loss α-PD1 T cell T cell α-PD1 α-PD1 sensitivity Immune evasion α-PD1 resistance STK11 mut STK11 mut cancer cell cancer cell TNG260 STK11 re-activati
Slide 32: STK11 loss-of-function mutations drive immune evasion
STK11 loss-of-function mutations drive immune evasion In vivo CRISPR screening identifies mediators of immune evasion STK11 deletion causes a-PD1 resistance reversion Control STK11 deletion (MC38) (MC38) Aggressive growth in immune HDAC1 competent mice a-PD1 resistant a-PD1 sensitive Days after the
Slide 33: TNG260 is a highly selective CoREST complex inhibitor
TNG260 is a highly selective CoREST complex inhibitor pan-HDAC inhibitors (vorinostat, panobinostat) Key points • CoREST-mediated deacetylation regulates transcription of a specific set of immune response genes • Sin3 is the predominant HDAC1 complex involved in • TNG260 alters expression of TNG260
Slide 34: TNG260 + α-PD1 induces complete regression in STK11-mutant xenografts
TNG260 + α-PD1 induces complete regression and prevents re-implantation in STK11-mutant xenografts TNG260 IC50 100nM, 10X CoREST complex selectivity TNG260 MC38 (STK11 deficient colon) • Potent, highly selective 3000 molecule with good Tumor pharmacologic properties re-implantation 2000 Day 69 • Mar
Slide 35: TNG260 + pembrolizumab first-in-human trial
TNG260 + pembrolizumab first-in-human trial DOSE PHASE 1/2 STUDY EXPANSION (ongoing) DOSE • STK11 mutations occur in ~15% STK11 mut ESCALATION NSCLC cancer NSCLC, 15% cervical, 10% carcinoma of unknown primary, 5% • Any solid tumor with breast and 3% pancreatic cancers STK11 mutation • Combination w
Slide 36: TNG260 proof-of-mechanism in phase 1/2 study
TNG260 proof-of-mechanism in phase 1 study Increased Intra-tumoral Increased histone acetylation Increased tumor PD-L1 staining cytotoxic T cells 8 80 350 300 60 250 6 40 150 20 4 6 100 4 2 50 2 0 0 0 40mg 80mg 120mg 120mg INT 40mg 80mg 120mg 40mg 80mg 120mg Dose TNG260 Dose TNG260 Dose TNG260 Pre-t
Slide 37: TNG260 summary
TNG260 summary PATIENT IND- DISCOVERY PROGRAM CLINICAL TRIALS STATUS SELECTION ENABLING Phase 1/2 Phase 3 CoREST STK11-mut Dose expansion ongoing, TNG260 cancers clinical data 2025 • STK11 mutations are associated with checkpoint inhibitor resistance in lung cancer patients • TNG260 is a novel, high
Slide 38: Financial Highlights and Milestones
FINANCIAL HIGHLIGHTS AND MILESTONES | 38
Slide 39: Multiple projected key milestones and strong balance sheet
Multiple projected key milestones and strong balance sheet Cash balance Clinical milestones ¨ TNG462 clinical data update 2025 • $258M cash, cash equivalents and marketable securities as of December 2024 ¨ TNG462 combination trials enrollment begin 1H 2025 • Cash runway into Q3 2026, including addit
Slide 40: Tango Therapeutics
Bij TANGO therapeutics
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