Full Press Release Details
Overview January 2025 | 1
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
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 the third quarter of 2026; the Company's belief that TNG260 may become a first-in-class oral CoREST inhibitor; the potential for TNG462 to have best-in-class tolerability; the Company's
planned and ongoing clinical trials, including the anticipated timing for enrollment and the timing to report results and updates of such trials; the Company's belief that TNG462 has the potential to be a best-in-class molecule for multiple
MTAP-deleted solid tumors; the potential for TNG462 activity in cholangiocarcinoma to indicate activity in lung and pancreatic cancer; the Company's expectations regarding its PRMT5 inhibitors as compared to competitor molecules; the
anticipated milestones for the Company's drug programs, including the timing for patient dosing, dose escalation, dose expansion, and clinical updates; the timing of initial and interim (and final) safety and efficacy or clinical activity data
and results from clinical trial(s); the timing of first-in-human and clinical trials; the timing of IND-enabling or registrational studies; the timing of clinical trial initiation, dose escalation, and dose expansion (including for combination
studies); the timing of disclosure for initial, interim, additional and final clinical trial results or safety and efficacy data; the expected benefits of the Company's development candidates and other product candidates (including for combination
studies); the potential for a large patient population to be treated with Tango's PRMT5 inhibitors; potential combination strategies and uses for PRMT5 inhibitors, including TNG462 and TNG456; the development plans for the PRMT5 franchise
(including future clinical trials); future clinical trial designs; TNG260 future clinical trials strategy and implementation; the significant patient opportunities for the Company's pipeline therapies; the Company's key future
milestones; the anticipated benefits of synthetic lethal drugs; expectations regarding the benefits and success of collaborations and combination clinical trials; and the anticipated benefits of its current and future product candidates including
those identified in the future through the Tango discovery platform; the potential of TNG462 to have broader and deeper clinical activity in MTAP-deleted solid tumors; expectations around TNG 456's clinical efficacy, including its potential to
treat glioblastoma and central nervous system metastases; the development and regulatory pathway for TNG462, TNG456, or TNG260. 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 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 the 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 clinical trial results; Tango's approach to the discovery and development of product candidates is novel and
unproven, 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 (including the potential impact of the BIOSECURE Act on our supplier of drug substance); 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, 2023, 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. | 2
COMPANY OVERVIEW | 3
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 GBM is MTAP-del - 15% of lung cancer is MTAP-del (7K pts/yr) - 20% of lung cancer is STK11 (22K pts/yr US) mut (25K pts/yr US) CNS penetrant in preclinical - ~35% of pancreatic cancer is studies
Proof-of-mechanism demonstrated MTAP-del* (15K pts/yr US) in lung cancer patients Highly potent and selective Durable responses in multiple Dose expansion cohort ongoing First patient dose planned cancer types
demonstrated in 1H2025 Phase 1/2 clinical update in 2025 phase I Potential best-in-class tolerability Actively enrolling 250 mg QD dose expansion cohort Phase 1/2 clinical update in 2025 O'Kane GM et al. Cancer
~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/yr
(US) Esophageal 21% Recent data from DFCI and others Gastric 9% demonstrate MTAP-deletion Renal 3% incidence in pancreatic cancer to Sarcoma 9% ~35% increasing the treatable Mesothelioma 32% patients to 15K/year (US)* Ovarian 3% Uterine 2%
Liver 3% Cholangio 11% Prostate 1% Head and Neck 15% O'Kane, G.M et al. Cancer Res., 2024 | 5
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
inactive state (MTA cooperative) Inactive MTA-PRMT5 complexes Active SAM-PRMT5 complexes predominate in MTAP-del cancer predominate in normal cells cells Non-MTA cooperative PRMT5 MTA-cooperative PRMT5 inhibitors
inhibitors are equally cytotoxic in preferentially kill MTAP-del cells normal and MTAP-del cells | 6
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 cancer cells
PRMT5 when MTA is bound TNG456 Essential methyl transferase regulates ~90 client proteins | 7
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 | 8
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 +pembrolizumab Lung
cancer Enrollment 1H2025 PRMT5 +SOC Pancreatic and Enrollment 2H2025 chemotherapy lung cancer MTAP-del Glioblastoma Enrollment 1H2025 TNG456 cancers STK11-mut Lung cancer Dose expansion ongoing CoREST TNG260 cancers All programs wholly owned by
TNG462 PRMT5 inhibition in MTAP-deleted cancers | 10
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 and
tolerability profile Phase 1/2 study ongoing, focused enrollment in 250 mg expansion cohort Key indication for development - MTAP-deleted lung and pancreatic cancer (~35K patients/yr US) mPFS Potency MTAP selectivity CNS exposure
(dose escalation) TNG462 4 nM 45X 24 weeks No TNG908 110 nM 15X 16 weeks Yes Data cutoff 20 October 2024 | 11
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
First monotherapy registration trials planned in 2L pancreatic Histology-agnostic solid tumors and lung cancer Enriched for cholangiocarcinoma, First patient dosed July mesothelioma, and bladder cancers 2023 59 patients enrolled (13
histologies) First patient dosed 39 evaluable patients at July 2024 active doses MTD 300 mg Data cutoff 20 October 2024 | 12
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
escalation cohort (AMG193 16 weeks, BMS not disclosed) Data continue to mature, with longest follow up in cholangiocarcinoma subset 43% TNG462 ORR in cholangiocarcinoma (n=7) compares favorably to competitor molecules 18%
BMS-504 (n=11) 15% AMG193 (n=13) Excellent tolerability profile with less fatigue and GI toxicity than competitors Ongoing enrollment focused on lung and pancreatic cancer TNG462 combinations with RAS inhibitors and
multiple standard of care regimens this year *59 patients enrolled, 13 histologies Data cutoff 20 October 2024 39 evaluable patients at active doses (160-300 mg QD) | 13
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 0 0 5 10 15 20 25
Time hours Error bars represent SEM | 14 Fold Over Free Cave Mouse Efficacy
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 Compares favorably to previously 0% Evaluable patients treated cholangiocarcinoma patients -16% receiving 2L chemotherapy* - ORR ~7% (standard of care) - PFS 14 weeks cPR uPR Data cutoff 20 October 2024 *Amonkar et al,
Future Oncology, 2024 | 15
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 appetite, fatigue,
Minimal nausea and fatigue 10% dysgeusia dysgeusia and CNS effects No dysgeusia ENA 2024 ESMO 2024 Currently evaluating 250 mg QD in lung and pancreatic cancer *Includes dose escalation patients at 160 mg QD Data cutoff 20 October 2024 |
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)
Carboplatin/paclitaxel in lung cancer (squamous) Targeting RAS-mut/MTAP-del cancers in collaboration with Revolution Medicines TNG462 + RMC-6236 in RAS-mut and MTAP-del lung and pancreatic cancer TNG462 + RMC-9805 in RAS
G12D-mut and MTAP-del lung and pancreatic cancer | 17
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 driver mutation
Clinical collaboration with Revolution Medicines to evaluate TNG462 + RMC-9805 (RAS G12D-selective) and TNG462 + RMC-6236 (RAS multi-selective) | 18
TNG908 Clinically active CNS-penetrant PRMT5 inhibitor replaced by
next-gen molecule TNG456 | 19
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
exposure below efficacy threshold Phase 1/2 study stopped enrollment November 2024 mPFS Potency MTAP selectivity (dose escalation) TNG908 110 nM 15X 16 weeks TNG462 4 nM 45X 24 weeks TNG456 20 nm 55X NA | 20
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