Tango Therapeutics : Corporate Presentation

Targeting tumor suppressor loss

to unmask vulnerabilities in cancer

for the next generation of precision medicines

Corporate Overview

May 2024

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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: Company has a cash runway into late 2026 (including for POC readouts for all four clinical programs); dose escalation is on-going in the TNG462 clinical trial and the TNG260 trial which is being evaluated in combination with pembrolizumab; dose escalation is on-going in TNG348 clinical trial; the Company expects to provide TNG908 and TNG462 clinical trial data in the second half of 2024; dose expansion on-going for TNG908; does expansion planned for 2Q 2024 for TNG462; TNG348 combination with Olaparib planned for 2Q 2024; early clinical data for TNG348 supports switch to once-a-day dosing; MAT2A inhibitors are indirect PRMT5 inhibitors and may add benefit in MTAP-del cancers in combination with TNG908 and TNG462; the dosing in cohorts 1 and 2 of the TNG908 clinical trial not yet within the predicted efficacious range; Company has a state-of-the- art discovery platform supporting a sustainable pipeline of novel precision oncology targets; Company has four on-going oncology clinical trials; TNG260 clinical exposures within the predicted efficacious dose range are well-tolerated; the anticipated milestones for the Company's drug programs, including the timing for patient dosing and dose escalation data and clinical updates, 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 clinical trials, the timing of IND-enabling studies, the timing of clinical trial initiation; the potential for a large patient population to be treated with Tango's PRMT5 inhibitors; Tango has a sustainable pipeline of novel precision oncology targets; the Company's lead program is a potentially first-in-class PRMT5 inhibitor that is synthetic lethal with MTAP deletion; TNG462 PK profile optimized for maximal target coverage; predictions regarding bone marrow suppression with use of PRMT5 inhibitors; there is a clear path to clinical POC for PRMT5 inhibitor in MTAP-null solid tumors with potential for histology-agnostic registration; potential combination strategies for PRMT5i; potential for histology- agnostic registration for PRMT5 inhibitor with broad based activity across tumor types; the Company will be pursuing novel combination therapies with inhibitors that have a complementary mechanism of action; TNG908 expansion cohorts provide optionality for multiple registration strategies; TNG908 expected to be brain penetrant in clinical study; TNG462 is potential best-in-class PRMT5 inhibitor (and has potential for broader and deeper clinical activity and is expected to have an increased therapeutic index and efficacy and extended target coverage); the development plans for the PRMT5 franchise (including future clinical trials); future clinical trial designs (including for TNG348); TNG260 and TNG348 future clinical trials strategy and implementation; the significant patient opportunities for the Company's pipeline therapies; the strong anti-tumor activity in HRD+ BRCA wt xenograft broadens the addressable patient population for TNG348; Tango has sufficient cash balance to fund operations into late-2026 (and is sufficient to achieve multiple projected key milestones); the Company's key future milestones; the anticipated benefits of synthetic lethal drugs; planned expansion cohort of the TNG908 phase 1/2 clinical trial for glioblastomas; and the anticipated benefits of future product candidates including those identified in the future through the Tango discovery platform. 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, 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 (and may utilize cash resources more quickly than anticipated and may exhaust cash resources prior to late-2026 or prior to POC readouts); Tango has limited experience with conducting clinical trials (and will rely on a third party 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 the 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 pre-clinical 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, scale back 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; 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 the 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.

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COMPANY OVERVIEW

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Tango Therapeutics

State-of-the-art discovery platform supporting a sustainable pipeline of novel precision oncology targets Gilead partnership to discover and develop up to 15 targeted immune evasion targets

Four ongoing precision oncology clinical trials

• Two PRMT5 inhibitors addressing large patient populations in multiple MTAP-del tumor types
• • TNG908 clinical data on GBM and solid tumors in 2H 2024
  • TNG462 clinical data in 2H 2024
• TNG260 (CoRESTi) to restore α-PD-L1 sensitivity in STK11-mut lung and other cancers
• TNG348 (USP1i) single agent and combo with olaparib in BRCA-mut and other DNA damage repair-deficient
• ovarian, breast, prostate and pancreatic cancers

Cash runway into late 2026 includes POC readouts for all four clinical programs

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A sustainable pipeline of novel precision oncology targets

PROGRAM	PATIENT	DISCOVERY	IND-	CLINICAL TRIALS	STATUS
SELECTION	ENABLING
				Phase 1/2	Phase 3
PRMT5						Dose expansion ongoing,
TNG908	MTAP-del					clinical data 2H 2024
PRMT5	cancers					Dose expansion planned 2Q 2024
TNG462						clinical data 2H 2024
CoREST	STK11-mut					Dose escalation ongoing
TNG260	cancers
USP1	BRCA1/2-mut
and other					Dose escalation ongoing
TNG348
HRD+ cancers
Multiple	Tumor
synthetic lethal	suppressor
targets	gene loss

Gilead optioned and licensed targets not listed

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A strong strategic partnership with Gilead

SCOPE

RESEARCH AND

DEVLOPMENT

RIGHTS

SHARED

ECONOMICS

TERMS

• 15 validated immune evasion targets
• Three targets licensed, two optioned to date
• Target discovery and validation at Tango with option to extend to clinical POC
• Gilead to lead post-POC development and commercialization
• Full rights to TNG260 and all cell autonomous targets not associated with immune evasion retained by Tango
• Option to co-develop/co-promote up to five programs
• 50/50 US profit/loss sharing on co-developed programs
• Low double-digit royalties on all other programs
• $175 million upfront
• $20 million equity
• Up to $110M to clinical POC, $410M per program and up to $6 billion in milestones

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SYNTHETIC LETHALITY FOR CANCER THERAPEUTICS

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Most cancer targets are not drugged yet

TUMOR

SUPPRESSOR

GENES

• Important drivers of cancer inactivated or deleted in almost all human cancers
• Not directly druggable

DNA DAMAGE

REPAIR

(USP1)

IMMUNE

EVASION

(CoREST)

CELL CYCLE

REGULATION

TRANSCRIPTIONAL

REGULATION

OTHER

(PRMT5)

SYNTHETIC

LETHALITY

Primary approach to targeting tumor suppressor gene loss

CRISPR

TECHNOLOGY

Essential for large scale synthetic lethal discovery efforts

UNDRUGGABLE

OR UNKNOWN

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PARP is the first clinically validated synthetic lethal drug target

BRCA1/2 mutation and PARP inhibition are a synthetic lethal pair

BRCA-mut	Normal
cancer cell
cell
	Niraparib

Placebo

+ PARPi		+ PARPi

CELLNO

DEATHEFFECT

• PARP inhibitors are approved in BRCA- mutant breast, ovarian, pancreatic and prostate cancer
• Synthetic lethal drugs inherently have a wide therapeutic index
• Multiple analyses suggest hundreds of synthetic lethal pairs exist in human cancer

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A robust synthetic lethal target discovery platform drives our precision medicine approach

Cell-autonomous	Immune evasion
target discovery	target discovery
CELL-BASED	IN VIVO
CRISPR	CRISPR
SCREENS	SCREENS

TANDEM

Computational target discovery

• Powerful CRISPR vector systems yield precision oncology targets with inherent patient selection strategies
• Custom libraries drive efficient discovery of novel targets
• TANDEM integrates large internal genetic perturbation data sets with massive public data sets

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