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PDAC Investor PresentationOctober 23, 2026
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Disclaimer and safe harbor statementCertain statements in this presentation may be considered forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including all statements regarding the intent, belief, or current expectation of Tango Therapeutics, Inc. (Tango) and members of the Tango senior management team. Forward-looking statements are not purely historical and may be accompanied by terminology such as “may”, “should”, “expect”, “intend”, “will”, “plan”, “path”, “achievable”, “milestones”, “goal”, “forecast”, “estimate”, “potential”, “anticipate”, “believe”, “predict”, or “continue”, or the negatives of these terms or variations of them or similar terminology. For example, express or implied statements concerning the following include or constitute forward-looking statements: the potential anticipated benefits, tolerability, efficacy and therapeutic profile of Tango's PRMT5 inhibitors, as both standalone treatments and in combination with RAS(ON)-inhibitors; Tango’s belief that it has a competitive advantage; Tango’s regulatory plans and expectations, including its expectation that the combination of vopimetostat and RAS inhibitors could (i) support a pivotal study in first line pancreatic cancer and an innovative and fast path to potential first line approvals and accelerated second line approval for pancreatic cancer and (ii) inform Tango’s development strategy in MTAP wild-type pancreatic cancer and other cancers; Tango’s expected cash runway; Tango’s plans for future trials and clinical milestones, including combination trials, and the design, initiation and the release of clinical data, and timing related thereto, for vopimetostat and TNG456, including with RAS(ON) inhibitors for vopimetostat; Tango’s expectations regarding its ability to secure sufficient clinical supply of daraxonrasib for its planned Phase 3 clinical trial evaluating vopimetostat with daraxonrasib; Tango’s expectations around regulatory communications and decisions related to its product candidates and clinical trials (including combination studies), including interactions with the U.S. Food and Drug Administration (FDA) and other regulatory authorities; the expected benefits of Tango’s development candidates and other product candidates (including for combination studies); Tango’s expectations around the size and value of the potential patient population for PRMT5 inhibitors (including for pancreatic cancers); potential market opportunity for Tango’s product candidates, if approved; potential combination strategies and uses for PRMT5 inhibitors, including vopimetostat and TNG456; and the development and regulatory plans for the PRMT5 franchise, including potential expansion into MTAP wild type tumors and other cancers. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Tango and its management at the time of this presentation, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: the benefits of product candidates seen in preclinical tests and analyses and clinical trials may not be evident when tested in later preclinical studies or in clinical trials or when used in broader patient populations (if approved for commercial sale); future clinical trial data releases may differ materially from initial, interim, updated, or final data from Tango’s current and future clinical trials; Tango has limited experience with conducting clinical trials (and does and will rely on third parties to operate its clinical trials) and may not be able to commence or progress its clinical trials when expected, may not be able to continue dosing, initiate dose escalation and/or dose expansion on anticipated timelines (or at all), and may not generate or report clinical trial results (including final, initial, interim, updated clinical trial results or additional safety and efficacy data and the establishment of proof-of-mechanism and proof-of-concept) in the anticipated timeframe (or at all); Tango’s pipeline products may not be safe and/or effective in humans; Tango may utilize cash resources more quickly than anticipated; Tango will need to raise capital in the future and if it is unable to raise capital when needed or on attractive terms (or at all), Tango would be forced to delay, reduce, or eliminate or discontinue some development programs or future commercialization efforts (which may delay filing of investigational new drug applications, dosing patients, initiation of dose expansion, reporting clinical trial results and filing new drug applications); the expected benefits of Tango’s product candidates in patients as single agents and/or in combination may not be realized; Tango may experience delays or difficulties in the initiation, enrollment, or dosing of patients in clinical trials or the announcement of initial, interim, or final clinical trial results; Tango’s product candidates may cause adverse or other undesirable side effects (or may not show requisite efficacy) that could, among other things, delay or prevent regulatory approval; Tango’s dependence on or a limited number third parties for conducting clinical trials and supplying and producing drug substance and drug product (including drug substance, which is currently sole sourced); Tango’s ability to enter into additional collaboration and supply agreements and to acquire, license, or otherwise obtain rights to additional products, product candidates, or molecules; government regulation may negatively impact Tango's business, including the potential approval of the BIOSECURE Act; the impact of trade restrictions such as sanctions, tariffs, reciprocal and retaliatory tariffs, legal actions or enforcement and inflation or interest rates on Tango’s business, financial condition, and results of operations; inadequate funding for or disruptions at the FDA or other government agencies may slow the time necessary for new drugs to be reviewed and/or approved or prevent these agencies from performing business functions on which the operation of Tango’s business may rely (which could negatively impact Tango’s business). Additional information concerning risks, uncertainties and assumptions can be found in Tango’s filings with the U.S. Securities and Exchange Commission (SEC), including the risk factors referenced in Tango’s Annual Report on Form 10-K for the year ended December 31, 2025, as may be supplemented and/or modified by its most recent Quarterly Report on Form 10-Q or other filings Tango may make with the SEC from time to time. You should not place undue reliance on forward-looking statements in this presentation, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Tango specifically disclaims any duty to update these forward-looking statements. Certain information contained in this Presentation relates to or is based on studies, publications, surveys and Tango’s own internal estimates and research. In addition, market data included in this presentation involve assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumption. Finally, while Tango believes its internal research is reliable, such research has not been verified by any independent source.
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Agenda for today 3 IntroductionMalte Peters, MD| President and Chief Executive OfficerVopimetostat + daraxonrasib combination data updateBrian Wolpin, MD | Dana-Farber Cancer Institute & Harvard Medical SchoolVopimetostat registration and expansion strategy in PDACAdam Crystal, MD, PhD | President of Research and DevelopmentUpcoming milestones and financial highlightsMatthew Gall | Chief Financial OfficerConclusionMalte Peters| Chief Executive OfficerQ&AAll Adam Crystal, MD, PhD Malte Peters, MD Matthew Gall Brian Wolpin, MD, MPH
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Introduction4Malte Peters, MD, President and Chief Executive Officer
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Leadership in PRMT5 inhibition anchors broad value creation opportunity 5 CLINICALLY VALIDATEDPotentially differentiated efficacy profile PHASE 3-READY DESIGNDefined regulatory pathDIFFERENTIATEDDemonstrated combinabilityEXPANSIONLeading the fieldEfficient Phase 3 design with ORR and PFS dual primary endpoints based on discussions with regulatory authorities Executing with a focused, experienced leadership team$1B on balance sheet*anticipated to support PDAC late-stage development and ongoing work82% ORR 88% 9-mo PFS rateWe believe reported efficacy measures exceed current and emerging benchmarks in PDAC, including 1L; favorable tolerability Clinical data and signals of differentiated safety and tolerability support potential for chemo-free combinations with multiple targeted agentsLargest body of clinical data of PRMT5 + RAS inhibitors; ERAS-0015 combination study planned; strongbiological rationale supports expansion into MTAP wild-type tumors *As of June 30, 2026.ORR, overall response rate; PFS, progression-free survival; PDAC, pancreatic ductal adenocarcinoma; 1L, first line.
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~60,000 U.S. pancreatic cancer patients per year~24,0001MTAP-deleted~36,000MTAP-WT~60,000 PDAC patients diagnosed/year~20,000MTAP-deleted~30,000MTAP-WT 6~9,200MTAP-deleted~13,800MTAP-WT1L treatment22L treatment2Patient population estimates by SEER, Kantar and others. 1L, first line; 2L, second line; WT, wild-type, PDAC, pancreatic ductal adenocarcinoma.1. Gorbokon, Cancers (Basel) 2025.2. King et al, Adv Ther 2022 and company estimates. Chemo-free regimens may increase patient access and benefit
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Brian Wolpin is a leader in the study and treatment of pancreatic cancer 7 Professor of Medicine, Harvard Medical SchoolRobert T. & Judith B. Hale Chair in Pancreatic Cancer, Dana-Farber Cancer InstituteDirector, Hale Family Center for Pancreatic Cancer Research and Gastrointestinal Cancer Center, Dana-Farber Cancer InstituteDirector, Dana-Farber – Lustgarten Foundation Dedicated Laboratory for Pancreatic Cancer ResearchMedical oncologist with clinical specialty in pancreatic cancerResearch laboratory dedicated to the investigation of pancreatic ductal adenocarcinoma (PDAC) biology and treatment
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Vopimetostat + daraxonrasib combination data update8Brian Wolpin, MD, MPHDana-Farber Cancer Institute & Harvard Medical School
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Evolution of standard of care for pancreatic cancer 9 RAS INHIBITORS +PRMT5 INHIBITORS RAS INHIBITORS CHEMOTHERAPYCurrent standard; Limited efficacyRASONQUE FDA approved based on improved PFS and OSIncreased response rate and prolonged durability; lower rates of rash observed1 Current Approved + Launched in US Potential for Further Advancement 1. Compared to single agent daraxonrasib, as of the data cutoff of August 20, 2026. Head-to-head trials have not been conducted; comparisons are based on cross-trial data and should be interpreted with caution.PFS, progression-free survival; OS, overall survival
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Vopimetostat selectively inhibits the cell essential gene PRMT5 in MTAP deleted cancer cells 10PRMT5activates PRMT5 in normal cellsSAMpartially inhibits PRMT5 by replacing SAMMTAMTAMTAMTAVopimetostatinhibits PRMT5 only in MTAP-del cancer cells when MTAis bound XXMTAPdeletion causes MTA accumulation only in cancer cells
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PRMT5 inhibition plus RAS inhibition is synergistic preclinically 11 Vopimetostat + Daraxonrasib: CAPAN1MTAP-null, KRASG12VPDAC CDXVopimetostat + Zoldonrasib: KP4MTAP-null, KRASG12DPDAC CDXVehicle20 mpk BID vopimetostat5 mpk QD daraxonrasib20 mpk BID vopimetostat + 5 mpk QD daraxonrasibVehicle20 mpk BID vopimetostat100 mpk QD zoldonrasib100 mpk QD zoldonrasib + 20 mpk BID vopimetostatVopimetostat and daraxonrasib dosed sub-therapeutically. Percent tumor volume change at the indicated time points in CAPAN1 or KP4 tumor-bearing mice following oral administration of vopimetostat, daraxonrasib, zoldonrasib, combination treatments, or vehicle (n=9/group for vehicle and single agent groups, n=12/group for combination group for KP4; n=8/group for CAPAN1). Data: Tango Therapeutics, data on file.QD, once daily; BID, twice daily.11
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First PRMT5 inhibitor combined with RAS inhibitors in the clinic Data extract 20 August 2026. Patients who received first dose at least 14 weeks prior to data cutoff were efficacy evaluable. All treated patients were safety evaluable. 2L, second line; NGS, next-generation sequencing; IHC, immunohistochemistry; QD, once daily.122L+ MTAP-del/RAS mut pancreatic and lung cancervopimetostat+daraxonrasibvopimetostat + zoldonrasibAny RAS mutG12D mutPhase 1 dose escalation trialVopimetostat + daraxonrasib:•Dose escalation range:200 mg – 250 mg vopimetostat QD+ 100 mg daraxonrasib QD•Evaluable patients Safety n=34Efficacy n=27MTAP status for enrollment:85% by NGS / 15% by IHC~95% concordance (NGS and IHC)•MTAP loss by NGS or IHC•1-2 lines prior systemic therapy in metastatic setting•ECOG PS 0 or 1•No prior PRMT5i or RASiKey inclusion criteria:
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Patient baseline characteristics Data extract 20 August 2026. a. One patient treated with vopimetostat+zoldonrasib had NSCLC and is omitted from this table. b. Treatment in the 1L setting was permitted in cases where standard of care was not appropriate. PDAC, pancreatic ductal adenocarcinoma; NSCLC, non-small cell lung cancer.13 Vopimetostat + zoldonrasib (PDAC) N=39aVopimetostat + daraxonrasib (NSCLC) N=5Vopimetostat + daraxonrasib (PDAC) N=2921 (53.8)3 (60)12 (41.4)Sex, male, n (%)66 (37, 81)55 (38, 71)66 (44, 74)Age, years, median (range)--2 (6.9)b0Prior anti-cancer therapies, n (%)18 (46.2)1 (20)10 (34.5)1 21 (53.8)3 (60)17 (58.6)2 -1 (20)-3+ 13 (33.3)2 (40)17 (58.6)0Baseline ECOG, n (%)26 (66.7)3 (60)11 (37.9)11 (3.4)Missing-1 (20.0) 15 (51.7)G12V KRAS mutation variant, n (%)--6 (20.7)G12R-1 (20.0)4 (13.8)Q61H/K/R --2 (6.9)G12A39 (100.0)2 (40.0)-G12D-1 (20.0)-G13C--2 (6.9)Missing31 (79.5)1 (20.0)21 (72.4)Liver metastases at baseline, n (%)
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Vopimetostat + daraxonrasib in MTAP-del 2/3L PDAC: ORR 82% 14-100-80-60-40-20020 2123333323223333322331 N=2282%ORR100%DCR Best Change in Tumor Size from Baseline (%)DL2DL1DL1DL1DL2DL1DL1DL2DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1Line of TherapyLegend:■Partial Response (PR)■Stable Disease (SD)Ongoing Therapy Data extract 20 August 2026. DL1: vopimetostat 200 mg+daraxonrasib 100 mg; DL2: vopimetostat 250 mg+daraxonrasib 100 mg.Treatment in the 1L setting was permitted in cases where standard of care was not appropriate. 11 of 18 responses were confirmed as of data extract date.PDAC, pancreatic ductal adenocarcinoma; DL, dose level; ORR, overall response rate; DCR, disease control rate. All responses now confirmed Note:13/22 (59%) of patients are 3LMedian duration of follow-up PDAC: 7.1 months (3.3-12.5)
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Consistent and promising results across PDAC and NSCLC Data extract 20 August 2026. DL1, vopimetostat 200 mg+daraxonrasib 100 mg; DL2, vopimetostat 250 mg+daraxonrasib 100 mg.Treatment in the 1L setting was permitted in cases where standard of care was not appropriate. PDAC, pancreatic ductal adenocarcinoma; NSCLC, non-small cell lung cancer.15 Best Change in Tumor Size from Baseline (%)-100-80-60-40-20020Line of Therapy231233333334232233333222331 DL2DL1DL1DL1DL1DL1DL2DL1DL1DL1DL2DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1DL1 ORR in NSCLC: 4/5 (80%)ORR in PDAC and NSCLC: 22/27 (81%)Dose level and indication:■DL1, PDAC■DL2, PDAC■DL1, NSCLCOngoing Therapy Median duration of follow-up PDAC: 7.1 months (3.3-12.5)NSCLC: 7.7 months (3.8-12.3)
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 Vopimetostat + daraxonrasib in MTAP-del PDAC: 88% 9-month PFS rate 16Legend:■Partial Response (PR)■Stable Disease (SD)Ongoing Therapy Line of TherapyExposure (Months)Key Metrics •88% 9-month PFS rate in PDAC (95% CI: 60, 97)•59% of PDAC patients are 3L3332322313223333232331Data extract 20 August 2026. All PDAC patients at DL1 and DL2 included in swimmer plot. Treatment in the 1L setting was permitted in cases where standard of care was not appropriate.PDAC, pancreatic ductal adenocarcinoma. CI, confidence interval; PFS, progression-free survival; 3L, third line; DL, dose level.
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Strong PFS trends in both second and third line MTAPdel PDAC 17No. at Risk121086420LoT0355772 0355913133 03911152122AllaData extract 20 August 2026. PDAC, pancreatic ductal adenocarcinoma; CI, confidence interval.a All lines of therapy includes two patients treated in the 1L setting. Key Metrics •88% 9-month PFS rate (95% CI: 60, 97)•No disease progression in 2L patients
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Vopimetostat + daraxonrasib was generally well-tolerated at dose level 1 18Data extract 20 August 2026. The safety population includes all patients who received at least one dose of the study drug combination prior to the data extract. Median duration of follow-up 5.8 (1.0-9.7). DLT, dose-limiting toxicity. SAE, serious adverse event. TRAE, treatment-related adverse event; DL, dose level. DL1: vopimetostat 200 mg+daraxonrasib 100 mg; DL2: vopimetostat 250 mg+daraxonrasib 100 mg.ᵃAt the time of the datacut, an event (Grade 2 anemia) was incorrectly captured in the EDC as a DLT; this has since been corrected. ᵇGrade 3 acneiform rash (resulting in dose reduction and continued treatment) and Grade 3 stomatitis and fatigue (withdrawn consent). •No new safety signals observed•No discontinuations due to TRAEs at DL1•20% dose reduction at DL1•No Grade 4 or 5 TRAEs•No related SAEsSafety SummaryDL2: PDAC(n=4)DL1:NSCLC(n=5)DL1: PDAC(n=25)n, (%)4 (100.0)5 (100.0)19 (76.0)Any TRAE1 (25.0)4 (80.0)9 (36.0)Grade 1-23 (75.0)1 (20.0)10 (40.0)Grade 3---Grade 4---Grade 5---SAE4 (100.0)3 (60.0)11 (44.0)Leading to Dose Modification4 (100.0)2 (40.0)10 (40.0)Interruption1 (25.0)2 (40.0)5 (20.0)Dose Reduction1 (25.0)--Leading to Withdrawal2 (50.0)ᵇ-a-Leading to DLT
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Vopimetostat + daraxonrasib was generally well-tolerated at dose level 1 19Data extract 20 August 2026. The safety population includes all patients who received at least one dose of the study drug combination prior to the data extract. DLT, dose-limiting toxicity. SAE, serious adverse event. TRAE, treatment-related adverse event. DL1, vopimetostat 200 mg+daraxonrasib 100 mg; DL2, vopimetostat 250 mg+daraxonrasib 100 mg.a. Includes TRAEs of rash, rash maculo-papular and dermatitis acneiform.Additionally, three patients across the study experienced ocular/visual events. One patient experienced blurred vision and two patients reported dry eye. All events were Grade 1. DL2: PDAC(n=4)DL1:NSCLC(n=5)DL1: PDAC(n=25)n, (%)Grade 3All GradesGrade 3All GradesGrade 3All GradesTRAEs occurring in ≥15% of Patients1 (25.0)4 (100.0)-5 (100.0)-11 (44.0)Rasha 1 (25.0)2 (50.0)-2 (40.0)-12 (48.0)Stomatitis/Mucositis-2 (50.0)-4 (80.0)-7 (28.0)Diarrhea1 (25.0)3 (75.0)-2 (40.0)-4 (16.0)Fatigue--1 (20.0)1 (20.0)3 (12.0)6 (24.0)Anemia-1 (25.0)-2 (40.0)-3 (12.0)Nausea-2 (50.0)---4 (16.0)Edema peripheral-1 (25.0)-1 (20.0)2 (8.0)4 (16.0)Thrombocytopenia-1 (25.0)-1 (20.0)-4 (16.0)Vomiting•No new safety signals observed•No discontinuations due to TRAEs at DL1•20% dose reduction at DL1•No Grade 4 or 5 TRAEs•No related SAEs•No Grade 3+ rash or mucositis/stomatitis at DL1•Low incidence of nausea, vomiting, diarrheaSafety Summary
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12%8%16%16%16%12%28%44%48%8%12%0% 20% 40% 60% 80% 100%NauseaThrombocytopeniaEdema peripheralVomitingFatigueAnemiaDiarrheaRashStomatitis/mucositis24%16% Vopimetostat + daraxonrasib demonstrated favorable RAS associated safety profile Data extract 20 Aug 2026. Data displayed are TRAEs most frequently associated with RAS inhibitors. 1. RASONQUE label; 2. Knoll, Cancer Research 2025; Drizyte-Miller, Cancer Research 2025 Pharmacokinetics and safetyDose level 1•Daraxonrasib AUC: 4303 hr*ng/ml (n=20, CV 40%)−Similar to daraxonrasib 300 mg single agent1•PRMT5 inhibition may improve RAS inhibitor- mediated on target toxicity due to upregulation of MAPK activation / pERK2•No Grade 4 or 5 TRAEsVopimetostat 200 mg + daraxonrasib 100 mg (PDAC)n=25 (TRAEs, % patients, Grade 1-3) Grades 1-2Grade 3 Median follow up: 5.3 months
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Clinically meaningful exposures and limited variability supportive of Phase 3 development Data extract 20 August 2026.21AUC0-24h (ng*h/mL) | Mean ± SDCV3815 ± 144438%Vopimetostat DL1 (n=18)4303 ± 172140%Daraxonrasib DL1 (n=20)Vopimetostat (ng/ml) Daraxonrasib (ng/ml)Time (Hour)
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Vopimetostat registration path22Adam Crystal, MD, PhD, President of Research and Development
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Vopimetostat + daraxonrasib: anticipated path to PDAC registrationLEAD PROGRAM~20,0001MTAP-del patients annually U.S.Larger near-term PDAC opportunityDemonstrated activity and durability profile82%ORR*88%9-mo PFS rateDefined 1L registration pathDesign informed by FDA guidanceFavorable safety + full target exposureNo grade 3 rash or stomatitis at dose level 1; reduced GI toxicityVopimetostat + daraxonrasib Data extract 20 August 2026. 1. Gorbokon, Cancers (Basel) 2025; King et al, Adv Ther 2022. *ORR 82%, 18/22. As of the data cut, 11 of 18 responses were confirmed. All unconfirmed responses subsequently have confirmed. PDAC, pancreatic ductal adenocarcinoma; 1L, first line; ORR, overall response rate; PFS, progression-free survival.23
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Key inclusion criteria:•MTAP loss by NGS •0 lines prior systemic therapy in metastatic setting•ECOG PS 0 or 1 Phase 3 study in 1L, MTAP-del PDAC anticipated to start 1H 2027 24 •Dual primary endpoints: ORR and PFS•OS as key secondary endpoint•Dose level 1 selected•Global, randomized study Primary Endpoints1L MTAP-delmetastaticpancreatic cancerN = 484Vopimetostat + daraxonrasibSOC chemo 1:1 randomizationSOC Chemo: investigator’s choice between 3 standard of care regimens (mFOLFIRINOX, NALIRIFOX, or GnP).SOC, standard of care; NGS, next-generation sequencing; ORR, overall response rate; PFS, progression-free survival; OS, overall survival.
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Advancing development path in 1L and 2L PDAC 25 Vopimetostat + daraxonrasib PDAC front line strategy supported by regulatory discussions *Subject to regulatory feedback. 1L, first line; 2L, second lineSOC chemo is investigator’s choice of mFOLFIRINOX, NALIRIFOX, or GnP.Study Objectives & Potential Regulatory OutcomesPrimary ReadoutPath Details1L PATH2L PATH*Randomized Controlled Trial vs. SOC chemoPhase 2 study vs. daraxonrasibORRPFSORR•Potential 1L approval•Assess contribution of components•Potential accelerated 2L approval
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Leadership in PRMT5 inhibition26Adam Crystal, MD, PhD
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Leadership in PRMT5 supports opportunities for indication expansionPDACVopimetostat + RAS inhibitors•Clinical activity shows that the combination biology can translate to marked combination activity•Encouraging tolerability relative to expected RAS-pathway toxicity•PRMT5i + RAS/MAPK inhibition is synergistica•PRMT5 inhibition causes hypersensitivity to MAPK pathway blockadebBiologic FoundationAdditional Opportunities•Clinical synergy with MAPK pathway may extend beyond MTAP-del PDAC•Potential in NSCLCand MTAP-WT PDACA broad combination strategy anchored in clinical and translational evidence a. Knoll, Cancer Research 2025; Drizyte-Miller, Cancer Research 2025b. Acquired Resistance to the PRMT5 Inhibitor Confers Collateral Sensitivity to MEK Inhibition in MTAP-Null Non-Small Cell Lung Cancer. Fu R, Wang Y, Rehman I, Bedford E, Sharif S, Nguyen ND, Powell RT, Adams A, Liu W, Wang S, He W, Lu Y, Liu B, Shah PA, Ahnert JR, Chen T, Peng W, Stephan CC, Liu X, Bedford MT, Xu H. Biomolecules. 2026 Aug 17;16(8):1198. doi: 10.3390/biom16081198.MTAPwt, MTAP wild type; PDAC, pancreatic ductal adenocarcinoma; NSCLC, non-small cell lung cancer.27
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Vopimetostat inhibited PRMT5 in MTAP WT cells, clinically Observed cAvg: 85 nM; IC50 MTAP WT cells: 109 nMSource: Cottrell, et al, Journal of Medicinal Chemistry 2025 and Tango data on file.28 PharmacokineticsPharmacodynamicsSafetyVopimetostat inhibited PRMT5 in MTAP wild type cells•Clinical exposure in DL1 = IC50 in MTAPwtcellsAt 200 mg vopimetostat results in on target related adverse events:•Fatigue•Thrombocytopenia•Anemia Clinical exposure in active range for MTAP WT cellsOn target AEs demonstrate PRMT5 inhibition in MTAP WT cellsDeep SDMA suppression at ≥160 mg in patients MTAP WT tissueMTAP del tumor
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Vopimetostat potentiates daraxonrasib in MTAP-WT PDAC cell lines at the exposure achieved clinically 29 Vopimetostat + daraxonrasib in vitro activityKey observations•Improved clinical activity in MTAP-WT PDAC cell lines with vopimetostat + daraxonrasib at clinical exposure•Clinical activity observed across all KRAS mutant variants tested (G12D, G12V , G12C and Q61H)* Denotes daraxonrasib doses < 300 mg clinical equivalent - doses chosen to target IC50; all other daraxonrasib doses are equivalent to 300 mg QD clinical doseAll vopimetostat doses are equivalent to 200 mg QD clinical doseSource: Cottrell, et al, Journal of Medicinal Chemistry 2025 and Tango data on file.PDAC, pancreatic ductal adenocarcinoma. Maximum Efficacy(% of DMSO)MTAP-WTMTAP-delVopimetostatDaraxonrasibVopimetostat + daraxonrasib Maximum Efficacy(% of DMSO)35% greater reduction from baseline
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Efficient path to expand the PRMT5 opportunity WT, wild type; POC, proof-of-concept; MTAP-del, MTAP-deleted, PDAC, pancreatic ductal adenocarcinoma; 1L, first line; NSCLC, non-small cell lung cancer. Potential for combination benefit to extend beyond MTAP-deleted cancersInforming Continued DevelopmentExpand opportunity in other tumor types, including NSCLCPotential to conduct study under existing Erasca collaborationBroaden 1L PDAC patient population to all patientsRapid, cost-efficient de-risking Clinically validated combinationvopimetostat +panRAS inhibitorEnroll MTAP-WT PDAC cohortAnticipated ~25-patient POC cohort Potential to reach more patients in PDAC & beyondMTAP-WT proof of concept could substantially broaden the addressable populationPotential to reach more patients in PDAC & beyondMTAP-WT proof of concept could substantially broaden the addressable population 30
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Upcoming milestones and financial highlights31Matthew Gall, Chief Financial Officer
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Near-term anticipated milestones support advancement of vopimetostat clinical development and efficient expansion opportunities 322L, second line; MTAP-del, MTAP-deleted; WT, wild type; NSCLC, non-small cell lung cancer. $1.0B cash and investments as of June 30, 2026, expected to support PDAC late-stage development and ongoing workRelease vopimetostat monotherapy dataNSCLCDATA READOUTRelease vopimetostat monotherapy dataNSCLCDATA READOUTJanuary 2027Release TNG456 monotherapy dataBrain-penetrant PRMT5 inhibitor in NSCLC, glioblastoma and other cancersDATA READOUTRelease TNG456 monotherapy dataBrain-penetrant PRMT5 inhibitor in NSCLC, glioblastoma and other cancersDATA READOUTJanuary 2027Advance NSCLC development strategyExpand RAS OpportunityAdvance Lead PDAC ProgramInitiate Phase 1/2 vopimetostat + ERAS-0015MTAP-del PDAC or MTAP-del, RAS-mutant NSCLCInitiate Phase 1/2 vopimetostat + ERAS-0015MTAP-del PDAC or MTAP-del, RAS-mutant NSCLC2H26Initiate Phase 1/2 vopimetostat + RAS combination study2L, MTAP-wild type PDACInitiate Phase 1/2 vopimetostat + RAS combination study2L, MTAP-wild type PDAC1H27Initiate Phase 3 vopimetostat + daraxonrasibFront line, MTAP-del PDACInitiate Phase 3 vopimetostat + daraxonrasibFront line, MTAP-del PDAC1H27
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Conclusion33Malte Peters, MD, President and Chief Executive Officer
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Compelling PDAC data support our registration strategy and broader franchise potential 34VALIDATED CLINICAL PROFILECompelling activity, durability and tolerability reinforce confidence in the clinical profileREGISTRATION-DIRECTEDDEVELOPMENTFocus shifts from establishing the signal to executing on a defined pivotal pathBROADER VOPIMETOSTATFRANCHISE POTENTIALCombinability and MTAP-WT biology support a broader long-term opportunity beyond the lead MTAP-del PDAC programLAUNCH PREPARATIONOrganizational readiness, leadership team in place, key activities underway MTAP-del, MTAP-deleted; WT, wild type; PDAC, pancreatic ductal adenocarcinoma.