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The next wave of targeted therapies in oncologyCorporate overviewJanuary 2026
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Disclaimer and safe harbor statementCertain 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 development and clinical trial objectives for Tango’s product pipeline (as individual therapies and combination therapies with other party’s drugs). In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “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 for the Company to have best-in-class oral PRMT5 inhibitors; the Company’s belief that it has a significant opportunity to treat multiple common cancers; the Company’s expected cash runway into 2028; the Company’s belief that TNG260 may be a first-in-class oral CoREST inhibitor; the potential for vopimetostat to have best-in-class tolerability; the Company’s expectations regarding its PRMT5 inhibitors as compared to competitor molecules, including in terms of safety and tolerability; the anticipated milestones and timing for the Company’s drug programs (including registrational studies), including the timing for clinical trial initiation, enrollment, patient dosing, dose escalation, dose expansion, and clinical updates; of initial, interim , and final safety and efficacy or clinical activity data and results from clinical trial(s); the Company’s expectations regarding a registrational trial for vopimetostat; the Company’s plans for and timing of combination trials for vopimetostat and TNG456, including with RAS(ON) inhibitors for vopimetostat and with abemaciclib for TNG456; the Company’s belief that vopimetostat has the potential to transform care in front line pancreatic cancer; the Company’s expectations regarding the combination study with RAS(ON) inhibitors, including future enrollment, study design, and the ability of early signs of activity and tolerability to translate to positive results; the Company’s expectations regarding TNG456’s predicted brain exposure may not be realized; the expected benefits of the Company's development candidates and other product candidates (including for combination studies); the Company’s expectations around the size and value of the potential patient population for PRMT5 inhibitors (including for lung and pancreatic cancers) and TNG260; potential combination strategies and uses for PRMT5 inhibitors, including vopimetostat and TNG456; the development plans for the PRMT5 franchise (including future single agent and combination clinical trials); future clinical trial designs; TNG260 future clinical trials strategy and implementation; expectations regarding the benefits and success of collaborations and combination clinical trials; and the anticipated benefits of its current and future product candidates; expectations around TNG456’s clinical efficacy, including its potential to treat glioblastoma and expectations around the brain exposure required for clinical efficacy; the development and regulatory pathway for vopimetostat, TNG456, TNG260 or TNG961; the Company’s belief that TN961 may be a first-in-class HBS1L degrader; and the Company’s belief that there is potential for single agent and vopimetostat combination activity for TNG961. 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. Drug development, clinical trials and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. 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: Tango has a limited operating history and has not generated any revenue to date from drug sales, and may never become profitable; future clinical trial data releases may differ materially from initial or interim data from our 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 any clinical trial, enroll and dose patients when expected and may not generate results in the anticipated timeframe (or at all); dosing (including dose expansion) in clinical trials may need be delayed or may be stopped for various reasons, including due to any potential issues at the site, safety issues or supply disruptions; any significant changes required to be made to an applicable IND application or protocol could significantly delay on-going clinical trials); the benefits of Tango pipeline products (stand-alone and as potential combination therapies) that are seen in preclinical experiments may not be present in clinical trials or in use commercially or may not be safe and/or effective in humans (and Tango or a third-party may not be able to obtain approval or commercial sales of any stand-alone or combination therapies); Tango has incurred significant operating losses and anticipates continued losses for the foreseeable future; Tango will need to raise capital in the future and if it is unable to raise capital when needed or on attractive terms, the Company would be forced to delay, reduce, or eliminate or discontinue some development programs or future commercialization efforts; Tango may be unable to advance its preclinical development programs into and through the clinic for safety or efficacy reasons or experience significant delays in doing so as a result of factors beyond Tango’s control; the expected benefits of our product candidates in patients as single agents and/or in combination may not be realized; the Company 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 approach to the discovery and development of product candidates is novel andunproven, which makes it difficult to predict the time, cost of development, and likelihood of successfully developing any products; Tango may not identify or discover development candidates (including next generation products) or may expend a portion of its limited resources to pursue a particular product candidate or indications and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success; delays or difficulties in the initiation, enrollment or dosing of patients in clinical trials could delay or prevent receipt of regulatory approvals or reporting trial results; our product candidates may cause adverse or other undesirable side effects that could, among other things, delay or prevent regulatory approval; our dependence on third parties for conducting clinical trials and producing drug product and drug substance (including the potential impact of the BIOSECURE Act on our suppliers); the impact of trade restrictions such as sanctions, tariffs, reciprocal and retaliatory tariffs, legal actions or enforcement and inflation rates on our business, financial condition, and results of operations; inadequate funding for or disruptions at the U.S. Food and Drug Administration 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 our business may rely (which could negatively impact our business), and uncertainty around the U.S. presidential administration's approach to governmental agencies and/or product candidate approvals may present challenges for our business or create a more costly environment in which to pursue the development of new therapeutic candidates; our ability to obtain and maintain patent and other intellectual property protection for our technology and product candidates or the scope of intellectual property protection obtained is not sufficiently broad; and delays and other impacts on product development and clinical trials from public health events. Additional information concerning risks, uncertainties and assumptions can be found in Tango’s filings with the SEC, including the risk factors referenced in Tango’s Annual Report on Form 10-K for the year ended December 31, 2024, as may be supplemented and/or modified by its most recent Quarterly Report on Form 10-Q. 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 assumptions. Finally, while Tango believes its internal research is reliable, such research has not been verified by any independent source.
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3 A clinical pipeline targeting multiple high value indicationsSTATUSCLINICAL TRIALSINDICATIONSPATIENT SELECTIONMOLECULETARGETPHASE 3PHASE 1/2PRE-CLINICALDose expansionPancreatic, lung,other non-CNS cancerMTAP-del cancersVopimetostat(TNG462)PRMT5Dose escalationPancreatic, lung cancerMTAP-del/RAS-mut(+RASi)Dose escalationGlioblastomaMTAP-del cancersTNG456IND-enablingSolid tumorsMTAP/FOCAD-delcancersTNG961HBS1LDose expansionLung cancerSTK11-mut/ RAS wtcancersTNG260CoREST
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•TNG456 (brain penetrant PRMT5 inhibitor) in phase 1/2 development for MTAP-del glioblastoma•TNG961 advanced to IND-ready for multiple MTAP-del/FOCAD-del solid tumors•$225M equity raise •$343M cash balance as of December 31, 2025*•Cash runway into 2028•Clinical data supporting vopimetostat as a potentially best-in-class PRMT5 inhibitor in multiple MTAP-del cancers•FDA supportive of pivotal study design in 2L MTAP-del pancreatic cancer•Vopimetostat + RAS(ON) inhibitors (Revolution Medicines) in MTAP-del/RAS-mut pancreatic and lung cancer initiated Key 2025 achievements 4 VopimetostatPipelineFinancial/CorporateAdvancing multiple clinical programs Creating value for patients * Financial information as of December 31, 2025 has not yet been audited
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Competitive advantage drives 2026 strategic execution 5•Planned pivotal protocol design including dose selection supported by FDA•MTAP selectivity and potency of vopimetostat provides potentially best-in-class PRMT5 suppression•Potentially best-in-class safety profile supports combinability with other molecules•First PRMT5 inhibitor clinical combination with RAS inhibitors may provide an innovative and fast path to front line approvalsLaunch pivotal study in 2L pancreatic cancerComplete vopimetostat/RASistudy to support 1L pivotal study in pancreatic cancerExpand vopimetostat data in lung/other cancers to support additional pivotal studiesEvaluate TNG456 efficacy in glioblastoma
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•Brain penetrant PRMT5 inhibitor being developed for glioblastoma•45% GBM is MTAP-del (~7K pts/yr US)•CNS penetrance predicted in preclinical studies•Dose escalation ongoing•Abemaciclib combo planned with evidence of single agent activity•Key indications*~20K pancreatic cancer~22K lung cancer ~20K histology selective cohort•2L MTAP-del pancreatic ca pivotal study start planned 2026•RAS(ON) inhibitor combo study ongoing•Potential best-in-class tolerability Pipeline poised to deliver meaningful clinical benefit in multiple common cancers with MTAP deletion 6 VopimetostatTNG456Potential best-in-class oral PRMT5 inhibitorsTNG961•HBS1L degrader synthetic lethal with FOCAD deletion•~30% of MTAP-del cancers also have FOCAD deletion•Single agent and vopimetostat combination activity in multiple preclinical models•Ready for phase 1 in 2026*MTAP-del pts, US/yr
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Vopimetostat (TNG462)7PRMT5 inhibition in MTAP-del cancers
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MTAP deletion is one of the most common genetic changes in cancer 8 Large unmet need•MTAP deletion confers sensitivity to PRMT5 inhibitors•Large opportunity for development in pancreatic and lung cancer, glioblastoma and multiple other common cancersMTAP del %Number of cases NSCLC15%Pancreatic*35%GBM/glioma45%Head and Neck16%Bladder25%Breast4%Uterine14%Melanoma20%Gastric14%Esophageal22%Mesothelioma31%Ovarian3%Renal1%Prostate1%Cholangio10%*Patient population sizes estimated by Clearview using data from SEER, Kantar, TCGA PanCancer Atlas and other sources.~60,000 treatable MTAP del cancers in the US annually
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MTAP-del cancers are uniquely sensitive to PRMT5 inhibition 9 SAMMTAMTAMTAMTAPRMT5VopimetostatTNG456activates PRMT5 in normal cellsSAMXMTAPXMTAP deletion occurs in 10-15% of cancersinhibit PRMT5 only in MTAP-del cancer cells when MTA is boundpartiallyinhibits PRMT5 by replacing SAMdeletion causes MTA accumulation only in cancer cells
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Vopimetostat and TNG456 selectively inhibit PRMT5 in MTAP-del cancers 10 Key points•Vopimetostat and TNG456 selectively kill MTAP-del cancer cells while largely sparing normal cells•Vopimetostat and TNG456 lock PRMT5-MTA into the inactive state (MTA cooperative)•Active SAM-PRMT5 complexes predominate in normal cells•Non-MTA cooperative PRMT5 inhibitors are equally cytotoxic in normal and MTAP-del cellsActive PRMT5SAMInactive PRMT5 Normal cellsMTAP-del cancer cells•Inactive MTA-PRMT5 complexes predominate in MTAP-del cancer cells•MTA-cooperative PRMT5 inhibitors preferentially kill MTAP-del cells
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Vopimetostat (TNG462) overview 11 •Oral, once a day, MTAP-selective PRMT5 inhibitor•Potential best-in-class molecule with superior target coverage and safety profile•A potential turning point in multiple hard to treat cancers, with demonstrated durable tumor control and favorable tolerability in the ongoing clinical trial, where current standard of care has neither•Key indications for development in approximately 60,000 patients/yr (MTAP-del, US)–Pancreatic cancer (~20,000 patients/yr)–Lung cancer (~22,000 patients/yr)–Histology selective (~20,000 patients/yr)•RAS combination studies ongoing in pancreatic and lung cancer•Pivotal study in 2L pancreatic cancer planned to start 2026, potential to be first-to-market in 2L MTAP-del pancreatic cancerPatient population sizes estimated by Clearview using data from SEER, Kantar and other sources.
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Vopimetostat phase 1/2 study 12 DOSE ESCALATION MTAP-del solid tumorsDOSE OPTIMIZATIONPancreatic cancerLung cancerHistology selective cancersAll pancreatic cancers are adenocarcinomas. All lung cancers are non-small cell histology.
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0102030405060708090100Vopimetostat response rate increases over time Based on total number of patients who achieved a partial response. Does not represent the total number of tumor evaluable patients.Data extract 18 Aug 2025.13Median follow-upORRNFollow-up7.4 mo20%127Any7.6 mo22%114> 4 mo9.3 mo27%85> 6 moAll patients dosed more than 6 months before data cutoff at 200 mg QD and aboveMedian time to RECIST response 3.5 months Vopimetostat phase 1/2 trial Time on study (months)2 4 6 8 % of total PRs
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Vopimetostat phase 1/2 data analysis – all indicationsTotal patients enrolledPatients atactive dosesTumor evaluable patients enrolled >6 mo before data cutoffAll patients except those awaiting first scan (n=11)All tumor evaluable patients n=179n=154n=94mPFSORRn=143n=131Spider plotData extract 1 Sept 2025.
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Vopimetostat demonstrates clear monotherapy activity across histologies Data extract 1 Sept 2025.Includes all tumor evaluable patients receiving 200 mg QD dose or higher more than 6 months prior to the data cutoff, including those remaining on study, progressed or withdrew. ORR/DCR in tumor evaluable patients, BOR rounded to the nearest whole number.Tumor evaluable is defined as MTAP-del patients with at least one scan. ORR defined as confirmed RECIST PR or unconfirmed PR with pending confirmation scan. A lung cancer patient who died of COVID before confirmation scan is included in ORR. Active doses are defined as 200 mg QD and above.15 Active doses >6 mo follow-upn=94Key points•ORR 27% in 16 different histologies•mPFS 6.4 months•DCR 78%•37/94 patients ongoing •Median follow-up 9.4 months•Good tolerability with no discontinuations for drug related events at 250 mg QDPatients remaining on treatment●
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Durable disease control with vopimetostat across cancer types Data extract 1 Sept 2025.mPFS calculation includes all patients (n=143); spider plot represents only tumor-evaluable subset of patients (n=131).16 All tumor evaluable patients at active doses (n=131)Key points•Overall mPFS 6.4 months−PR pts 11.1 months−SD pts 7.3 months−PD pts <2 months•Median time to response 3.5 monthsTime on treatment (months)Time on treatment (months)Partial responseStable diseaseProgressive disease
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Vopimetostat 250 mg QD has a potential best-in-class safety profile Data extract 1 Sept 2025.17 Related AEs in ≥5% pts (n=84)Key points•Median follow-up 6.1 months•8% dose reduction•0% discontinuation for related events •No grade 4-5 related events•Low grade GI side effects Vopimetostat AE profile suggests good tolerability in combination with chemo- and targeted therapiesGrade 1Grade 2Grade 3
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Vopimetostat pancreatic cancer cohort Data extract 1 Sept 2025*Includes one 1L patient.18 64 pancreatic cancer patients at active doses*One prior therapy for advanced disease•n=29 pts•10/29 pts more than 6 months since enrollment (8 pts tumor evaluable)Two or more therapies for advanced disease •n=34 pts•29/34 pts more than 6 months since enrollmentEnrollment by starting dose (QD)•200 mg n=22 •250 mg n=35•300 mg n=6•600 mg n=1
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Pancreatic cancer demographics for vopimetostat phase 1/2 study 19 3L+2L3429N (patients)6664Median age (yrs)Performance status13 (38%)9 (31%)ECOG 021 (62%)20 (69%)ECOG 1Prior therapies34 (100%)29 (100%)Prior systemic therapy11 (32%)6 (21%)Neo-adjuvant therapy14 (41%)9 (31%)Adjuvant therapy34 (100%)29 (100%)Advanced/metastatic settingPrior lines of therapy in metastatic settingNA29 (100%)1 19 (56%)NA2 9 (27%)NA3 6 (18%)NA>4 21Median number of prior treatment regimentsData extract 1 Sept 2025.
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Vopimetostat mPFS is 7.2 months in 2L pancreatic cancer Data extract 1 Sept 2025. All 2L pancreatic cancer patients at 200 mg QD and above.*ORR ranging from 3-17% reported in published literature.20 Vopimetostat in 2L and 3L+ pancreatic cancerSummaryVopimetistat•2L mPFS 7.2 mo•2L ORR 25%̶Overall ORR 15%•Overall DCR 71%•Median follow-up 7.8 moChemotherapy historical control trials•2L mPFS 2-3.5 mo•2L ORR ~10%* 95% CI(mo)mPFS(mo)CensoredEventsNLine of therapy1.7 - NR7.21212242L1.8 – 7.74.1920293L+Time on study (weeks)2L PDAC3L+ PDAC
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Vopimetostat mPFS in 2L pancreatic cancer more than twice historical SOC trials Data extract 1 Sept 2025.a. Ikushima, ESMO Open, 2025, Rodon et al, ESMO 2025.b. All tumor evaluable 2L patients at active doses and the only 2L patient at 160 mg QD. Historical data are derived from different clinical trials at different points in time and head-to-head clinical trials have not been conducted. 21 Key points•ORR in 2L PDAC 25% (2/8 evaluable pts)•Vopimetostat 2L mPFS 7.2 mo•SOC chemotherapy mPFS 2-3.5 mo•Vopimetostat pivotal study control arm may have lower mPFS than historical controls, increasing probability of success 95% CI(mo)mPFS(mo)CensoredEventsVopimetostat(n)2.9 - NR7.2131225b Recent studies show MTAP deletion confers poor prognosis due to concurrent CDKN2A deletiona
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Vopimetostat monotherapy pivotal trial in 2L pancreatic cancer 22 Pivotal study start planned 2026Planning for 2L registration•FDA supportive of study design•Rapid enrollment of ~300 patients anticipated given high unmet medical need in this patient population2L MTAP-del pancreatic cancervopimetostat 250mg QD n~150SOC chemotherapyn~150
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Vopimetostat + zoldonrasib has striking efficacy in preclinical models *Vopimetostat exposure in combination formulation predicted equivalent to 30 mpk monotherapy23 Vopimetostat + zoldonrasibKey points•Pancreatic cancer is a RAS-addicted cancer•Almost all MTAP-del pancreatic cancers have a RAS mutation•~40% MTAP del pancreatic ca is RAS G12D mut•Similar preclinical data with daraxonrasib•Clinical collaboration with Revolution Medicines to evaluate vopimetostat + zoldonrasib (RAS G12D-selective inhibitor) and vopimetostat + daraxonrasib (RAS multi-selective inhibitor)KP4MTAP-null, KRASG12D PDAC CDX
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Encouraging early activity in ongoing vopimetostat + RAS(ON) inhibitor clinical study 24 Study update•Ongoing robust enrollment•30 patients dosed−14 pts with vopimetostat/daraxonrasib−16 pts with vopimetostat/zoldonrasib•Both combinations well tolerated at active exposures of all molecules •No unexpected adverse events•Early efficacy data encouragingDOSE ESCALATION 2L+ MTAP-del/RAS mut pancreatic and lung cancervopimetostat + daraxonrasibvopimetostat + zoldonrasibAny RAS mutG12D mutSafety and efficacy data update planned 2026Enrollment data as of 24 December 2025
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Vopimetostat + RASi strategy for 1L pancreatic cancerRAS inhibitors likely to replace chemotherapy as SOC in 1L pancreatic cancer•More than 90% of pancreatic cancers are RAS-driven•Almost all MTAP-del pancreatic cancers have a RAS mutation •~18k pts with MTAP-del and RAS-mut pancreatic cancer annually in the U.S.Potential path to vopimetostat 1L pivotal study with chemo-sparing RASi combinations•Encouraging early activity and robust enrollment in ongoing study in 2L+ pancreatic and lung cancer•Addition of 1L pancreatic cancer cohort to ongoing study planned 2026•Phase 1/2 combo data in 2026 could support rapid move into 1L pancreatic cancer pivotal study-Single agent daraxonrasib 2L pancreatic ca ORR 29%, 1L pancreatic ca 47%, 2L+ lung ca 39%*-Single agent zoldonrasib 2L+ pancreatic ca ORR 30%*•First PRMT5 inhibitor being clinically evaluated in combination with RAS inhibitors*Revolution Medicines corporate deck November 2025
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Vopimetostat lung cancer cohort 26 41 lung cancer patients at active dosesOne or more prior therapy for advanced disease•n=41 patients•12/41 pts more than 6 months since enrollment •Median follow-up 4.7 monthsEnrollment by starting dose (QD)•200 mg n=13*•250 mg n=26•300 mg n=2Data extract 1 Sept 2025*Includes two patients enrolled at 160 mg QDFully enrolled, emerging data consistent with expectationsUpdate planned 2026
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Vopimetostat histology selective cohort Data extract 1 Sept 2025Includes all patients enrolled in the study more than 6 months prior to the data cutoff, including those remaining on study, progressed or withdrew.27 47 histology selective patients at active doses Histology selective cohort analysis excludes pancreatic cancer, lung cancer and sarcomaOne or more prior therapy for advanced disease•n=47 patients•41/47 pts more than 6 months since enrollment Enrollment by starting dose (QD)•200 mg n=15 •250 mg n=19•300 mg n=11•600 mg n=2
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Vopimetostat 49% ORR in histology selective cohort Data extract 1 Sept 2025.ORR in tumor evaluable patients, BOR rounded to the nearest whole number. 28 Tumor evaluable pts at active doses with >6 months follow-up (n=37)Key points•ORR 49% •mPFS 9.1 months •DCR 89%•21/37 patients ongoing•Median follow-up 9.5 months•Excludes sarcoma, pancreatic and lung cancerCholangiocarcinomaMesotheliomaHead and neckCarcinoma of unknown primaryEsophagealOther (8 histologies) Ongoing●
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Vopimetostat 9.1 mo mPFS more than twice historical SOC trials in multiple indications 29 mPFS(95% CI)9.1 months(6.5 – 12.0)Durable activity in multiple late line, difficult to treat cancers provides: •Further evidence of robust single agent activity •Additional optionality for development in large patient population with high unmet need Data extract 1 Sept 2025.Historical data are derived from different clinical trials at different points in time and head-to-head clinical trials have not been conducted.
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Vopimetostat has the potential to be best-in-class and first-to-market for large patient populations with high unmet need 30 •Overall response rate (ORR) 27% across cancer types currently best-in-class* , FDA supportive of 250 mg QD go-forward dose •Median progression-free survival (mPFS) 7.2 months and ORR 25% in 2L MTAP-del pancreatic cancer supports planned pivotal study start 2026•Robust enrollment in ongoing combination study of vopimetostat + RAS(ON) inhibitors in 2L+ MTAP-del pancreatic and lung cancer patients, expansion to first line (1L) cohort planned•Lung cancer cohort fully enrolled (n=41), emerging data consistent with expectations, update planned 2026•49% ORR and mPFS 9.1 months in histology selective cohort of multiple late line cancer types (excluding sarcoma) provides further evidence of strong vopimetostat activity and additional optionality for development •Potential best-in-class safety and tolerability profile with no drug-related dose discontinuations and ~8% dose reduction suggests good combinability with other agentsData extract 1 Sept 2025*Based on previously reported data, BMS504 ORR 23% (ASCO 2025), AMG193 ORR 21% (ESMO 2024). No head-to-head studies have been conducted.The histology selective cohort includes all patients excepting lung cancer, pancreatic cancer and sarcoma patients.
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TNG45631PRMT5 inhibition in MTAP-deleted cancers
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TNG456 is a next-generation CNS-penetrant PRMT5 inhibitor 32 Brain penetrance provides potential to address high unmet need in glioblastoma•Predicted brain exposure well above efficacy threshold•In development for MTAP-del glioblastoma (7,000 patients/yr US)1CNS exposureMTAP selectivityPotency0.5-1X plasma55X20 nMTNG456-45X4nMVopimetostat1. SEER;CBTRUS
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•Dose escalation ongoing •Abemaciclib combination to start with evidence of single agent activity in GBM•FDA Fast Track designation•FDA Orphan Drug Designation for glioblastomaTNG456 phase 1/2 clinical study in MTAP-del solid tumors 33DOSE ESCALATION TNG456DOSE EXPANSIONGlioblastomaSummaryNSCLC
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TNG456 exposure in brain predicted to be in efficacious range at achievable doses *based clinical PK at 100 mg BID (plasma)TNG456 brain exposure modeled at 50% of plasma34 Key points•TNG456 5X more potent and 3X more selective than TNG908 in preclinical models•Predicted brain exposure 5-6X efficacy threshold at 500 mg BID•Measured TNG908 brain exposure at MTD below efficacy thresholdExpected TNG456 exposure vs observed TNG908 exposureEfficacy threshold Predicted TNG456 CNS exposure at 500 mg BIDTNG908 (CSF)TNG908 (plasma)024681012140 5 10 15 20 25Fold Over Free Cave Mouse EfficacyTime hoursPredicted TNG456 exposure at 500 mg BID
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TNG26035CoREST inhibition in STK11-mutant cancers
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STK11-mut lung cancer responds poorly to checkpoint inhibitor therapy 36 1L lung cancer OS significantly lower in STK11 mut vs WT cancersKey points•~10% of non-small cell lung cancer is STK11 mut/KRAS WT•STK11 mutations associated with checkpoint inhibitor resistance in NSCLC•STK11 included on all commercial NGS panels•Median overall survival 6.4 mo (STK11mut) vs 12.7 mo (WT)De Giglio, A., et al. Lung Cancer. 2025.
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TNG260 restores a-PD-1 responsiveness to STK11-mutant cancers in preclinical models 37 Selective CoREST complex inhibitionTNG260 reverses PD1 resistance caused by STK11 loss-of-function TNG260HDAC1 complexes Tumor volume (mm3) MC38STK11-mutant colon (engineered syngeneic)Tumor re-implantation•5/8 mice with complete tumor regression at day 34•5/5 mice with complete regression rejected tumor re-implantation
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•mPFS 6.7 mo•SOC mPFS*−-PD1 after pembro failure ~8 wks−2L docetaxel ~14 wks•No clinical activity in STK11/KRAS mut lung or other cancer typesTNG260 + pembrolizumab in checkpoint inhibitor refractory STK11-mut lung cancer 38 DOSE ESCALATION (n=41)DOSE EXPANSION(ongoing)STK11-mut/KRAS WTlung cancerEarly proof-of-concept data in STK11-mut/KRAS WT lung cancer *Parekh, D., et al. J. Clin. Oncol. 42, 8032 (2024)Data as of 22 Sept 2025TNG260 80 mg QD + pembrolizumab STK11/RAS mut lung(n=8)STK11KRAS WT lung(n=5)Other STK11-mut solid tumors (n=8)21 evaluable patients at active doses
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TNG260 converts STK11-mut immune microenvironment from unresponsive to responsive 39 PD-L1 tumor scoreIntra-tumoral cytotoxic T cellsTumor cells Cytotoxic T cellsIncreased tumor cell surface PD-L1 at 80 mg TNG260Increased tumor T cell infiltration at 80 mg TNG260Pre-treatment On treatment Pre-treatment On treatment 10%75%
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TNG260 80 mg QD is well-tolerated 40 Summary•TNG260 well-tolerated at 80 mg •Expected on-target AEs include cytopenia and fatigue−Drug interruptions 38% (n=9)−Dose reductions 17% (n=4)−Drug withdrawals 4% (n=1)•Enrolling dose expansion at 80 mg QDSafety profile at 80 mg QD (n=24) Data as of 22 Sept 2025
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All patients receiving active doses of TNG260 as part of dose escalation 41 Combination treatmentKRAS WT NSCLCKRAS Mut NSCLCNon-lung histologies (prior lines) -PD-1(prior lines) -PD-1(prior lines) -PD-1Data as of 22 Sept 2025
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TNG260 + pembrolizumab 27 weeks mPFS more than twice historical SOC trials 42 STK11-mut/KRAS WT lung cancerDose escalation patients at active dosesKey points•Early proof-of-concept (n=5)•mPFS 6.7 mo•Historical mPFS1−-PD-(L) 2.5 mo−2L docetaxel 3-4 mo•1/5 PR (ORR 20%) •Dose expansion ongoing, planned total enrollment n=20(prior lines) -PD-1SOC mPFS10 weeks*Patient was inevaluable by RECIST criteria due to one non-target brain lesion not able to be scanned at week 55. All lesions scanned thereafter1. Parekh, D., et al. J. Clin. Oncol. 42, 8032 (2024)Data as of 22 Sept 2025*All patients previously progressed on checkpoint inhibitor therapy Combination treatment
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TNG96143HBS1L degrader for FOCAD-del cancers
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FOCAD deletion and HBS1L are a synthetic lethal pair 44 FOCAD deletion occurs in one third of MTAP-del cancers FOCAD deletion confers HBS1Ldependency for RNA stability Releaseribosome PELOHBS1L SKI complexFOCAD Extract and degrade mRNATNG961 (HBS1L degrader)Vopimetostat
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TNG961 drives tumor regression in FOCAD-del/MTAP-del preclinical models 45 Strong xenograft activity across lineagesTNG961•Potent and selective HBS1L molecular glue degrader•IC50 110 nM•100X selectivity for FOCAD del vs WT cells•IND-enabling studies complete with very clean safety profile−Starting dose within the predicted active range supportedMIAPACA2PDAC NCI-H838NSCLC
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Financial highlights and milestones46
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Multiple projected key milestones and strong balance sheet 47 2026 clinical milestonesCash balanceVopimetostat lung ca dataVopimetostat + daraxonrasib/zoldonrasib data 2L PDAC pivotal study start TNG456 data •$343M cash, cash equivalents and marketable securities as of December 31, 2025*•Cash runway into 2028* Financial information as of December 31, 2025 has not yet been audited