Tango Therapeutics Announces First Patient Dosed in Phase 1/2 Trial of TNG462 plus Revolution Medicines’ Daraxonrasib or Zoldonrasib in Patients with RAS-Mutant MTAP-deleted Pancreatic or Lung Cancer

Rhea-AI Summary

Tango Therapeutics (NASDAQ: TNGX) has initiated dosing in a Phase 1/2 trial combining its TNG462 with Revolution Medicines' daraxonrasib or zoldonrasib in patients with MTAP-deleted and RAS mutant metastatic pancreatic or lung cancer.

The study aims to evaluate safety, pharmacokinetics, pharmacodynamics, and antitumor activity. TNG462, a MTA-cooperative PRMT5 inhibitor, is also being studied as monotherapy with data expected in H2 2025. The monotherapy results will inform a registrational trial in pancreatic cancer and advance the lung cancer development plan.

Positive

• First patient dosed in combination trial targeting both MTAP-deleted and RAS mutant cancers
• Strong preclinical combination activity demonstrated
• Single agent clinical data shows good tolerability and activity in target cancers
• Monotherapy data expected in H2 2025 to inform registrational trial

Negative

• None.

Insights

Oncology Clinical Trials Expert

Tango's first patient dosed in combination therapy trial represents significant advancement for MTAP-deleted cancer treatment strategy with potential registrational pathway.

Tango Therapeutics has reached a significant clinical milestone with the first patient dosed in their combination therapy trial investigating TNG462 with Revolution Medicines' RAS inhibitors (daraxonrasib or zoldonrasib) for patients with MTAP-deleted and RAS-mutant pancreatic or lung cancers. This development follows strong preclinical evidence showing synergistic activity between these compounds.

The biological rationale is compelling. MTAP deletions create a vulnerability that TNG462 exploits as a MTA-cooperative PRMT5 inhibitor, while Revolution's compounds target the RAS mutations that drive tumor growth. The combination addresses two cancer-driving mechanisms simultaneously, potentially enhancing efficacy beyond single-agent approaches.

Importantly, the company disclosed a clear development timeline, with monotherapy data expected in H2 2025 that will inform a potential registrational trial in pancreatic cancer and advance their lung cancer program. The emphasis on pancreatic cancer is particularly noteworthy given its poor prognosis and limited treatment options.

This trial represents Tango's strategic expansion from monotherapy to rational combinations that could address specific genetic subpopulations with high unmet need. The target population is well-defined: almost all MTAP-deleted pancreatic cancers and approximately 30% of lung cancers have co-occurring RAS mutations, creating a clear patient selection strategy for these precision therapies.

BOSTON, June 27, 2025 (GLOBE NEWSWIRE) -- Tango Therapeutics, Inc. (NASDAQ: TNGX), a clinical-stage biotechnology company committed to discovering the next generation of precision cancer medicines, today announced that the first patient has been dosed in the Phase 1/2 trial of TNG462 and Revolution Medicines’ daraxonrasib (RAS(ON) multi-selective inhibitor) or zoldonrasib (RAS(ON) G12D-selective inhibitor) in patients with MTAP-deleted and RAS mutant metastatic pancreatic or lung cancer.

“Almost all MTAP-del pancreatic and approximately 30% of lung cancers have a co-occurring RAS mutation, and preclinical data show strong combination activity of TNG462 with either daraxonrasib or zoldonrasib. Single agent clinical data to date have demonstrated these molecules to be well-tolerated and active in pancreatic cancer and lung cancer, supporting the potential for these combinations to become transformative therapies.” said Adam Crystal, M.D., Ph.D., President, Research and Development of Tango Therapeutics. “The potential of these combinations further strengthens our conviction that TNG462 may play a major role in changing the treatment paradigm for patients with MTAP-deleted cancers.”

The Phase 1/2 combination trial (NCT06922591) is evaluating safety, pharmacokinetics, pharmacodynamics and antitumor activity in TNG462 in combination with daraxonrasib and TNG462 in combination with zoldonrasib in pancreatic and lung cancer patients with an MTAP deletion and a co-occurring RAS mutation.

TNG462, a potentially best-in-class MTA-cooperative PRMT5 inhibitor, is currently being evaluated as monotherapy in a Phase 1/2 trial, with data expected in the second half of 2025. This upcoming monotherapy data update is anticipated to provide sufficient information to inform a registrational trial in pancreatic cancer next year and advance the development plan for lung cancer.

About Tango Therapeutics

Tango Therapeutics is a clinical-stage biotechnology company dedicated to discovering novel drug targets and delivering the next generation of precision medicine for the treatment of cancer. Using an approach that starts and ends with patients, Tango leverages the genetic principle of synthetic lethality to discover and develop therapies that take aim at critical targets in cancer. For more information, please visit www.tangotx.com.

Forward-Looking Statements

Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events, Tango’s future operating performance and goals, the anticipated benefits of therapies and combination therapies (that include a Tango pipeline product), as well as the expectations, beliefs and development objectives for Tango’s product pipeline and clinical trials. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “goal”, “estimate”, “anticipate”, “believe”, “predict”, “designed,” “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology. For example, implicit or explicit statements concerning the following include or constitute forward-looking statements: the potential benefits of TNG462 as a monotherapy and in combination with and daraxonrasib or zoldonrasib; monotherapy clinical data to date support the potential for these combinations (TNG462 and daraxonrasib or zoldonrasib) to become transformative therapies; the potential of these combinations (TNG 462 and daraxonrasib or zoldonrasib) to strengthen our conviction that TNG462 may play a major role in changing the treatment paradigm for patients with MTAP-deleted cancers; data from the phase 1/2 trial for TNG462 monotherapy is expected in the second half of 2025 and is anticipated to provide sufficient information to inform a registrational trial in pancreatic cancer in 2026 and advance the development plan for lung cancer; the potential for TNG462 to be a best-in-class MTA-cooperative PRMT5 inhibitor; and the expected timing of: (i) development candidate declaration for certain targets; (ii) initiating IND-enabling studies; (iii) filing INDs; (iv) clinical trial initiation, dose escalation and dose expansion (including for combination studies); and (v) disclosing initial, interim, updated, additional and final clinical trial results (including for combination studies. 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. 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 (including TNG462 as a monotherapy and in combination with other therapies) seen in preclinical tests and analyses 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); Tango has limited experience conducting clinical trials (and does and will continue to rely on a third party to operate its clinical trials) and may not be able to commence its clinical trials (including opening clinical trial sites, dosing the first patient, and continued enrollment and dosing of an adequate number of clinical trial participants) when expected, may not be able to continue dosing, initiate dose escalation and/or dose expansion on anticipated timelines, 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); future clinical trial data releases may differ materially from initial or interim data from our current and future clinical trials; Tango’s pipeline products may not be safe and/or effective in humans; Tango has a limited operating history and has not generated any revenue to date from product sales, and may never become profitable; other companies may be able to identify and develop product candidates more quickly than the Company and commercially introduce the product prior to the Company; the Company may not be able to identify development candidates on the schedule it anticipates due to technical, financial or other reasons; the Company may not be able to file INDs for development candidates on time, or at all, due to technical or financial reasons or otherwise; the Company may utilize cash resources more quickly than anticipated; Tango will need to raise capital in the future and if we are unable to raise capital when needed or on attractive terms, we would be forced to delay, scale back or discontinue some of our development programs or future commercialization efforts (which may delay filing of INDs, dosing patients, initiation of dose expansion, reporting clinical trial results and filing new drug applications); the Company may be unable to advance our preclinical development programs into and through the clinic for safety or efficacy reasons or commercialize our product candidates or we may experience significant delays in doing so as a result of factors beyond Tango’s control; the Company may not be able to realize the benefits of orphan drug or Fast Track designation (and such designations may not advance any anticipated approval timelines); 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 may not identify or discover additional product candidates or may expend limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success; the Company’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; our dependence on one or a limited number third parties for conducting clinical trials and producing drug substance and drug product (including drug substance, which is currently sole sourced) increases the risk that we will not have sufficient quantities of our product candidates or products or at an acceptable cost; government regulation may negatively impact the Company’s business, including the potential approval of the BIOSECURE Act; our business, financial condition and results of operations may be negatively impacted by global economic conditions, including trade restrictions and tariffs, legal actions or enforcement and inflation rates; 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); 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; and 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. Additional information concerning risks, uncertainties and assumptions can be found in Tango’s filings with the Securities and Exchange Commission (SEC), including the risk factors referenced in Tango’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, as 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 press release, 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.

Investors and Media:

Elizabeth Hickin

IR@tangotx.com

media@tangotx.com

FAQ

What is the purpose of Tango Therapeutics' (TNGX) Phase 1/2 trial with TNG462?

The trial evaluates TNG462 in combination with daraxonrasib or zoldonrasib for treating patients with MTAP-deleted and RAS mutant metastatic pancreatic or lung cancer.

When will Tango Therapeutics (TNGX) release TNG462 monotherapy data?

Tango expects to release TNG462 monotherapy data in the second half of 2025.

What percentage of lung cancers have MTAP deletion and RAS mutation?

Approximately 30% of lung cancers have a co-occurring RAS mutation with MTAP deletion.

What are the endpoints of TNGX's Phase 1/2 combination trial?

The trial evaluates safety, pharmacokinetics, pharmacodynamics, and antitumor activity of TNG462 combinations.

What is TNG462's mechanism of action?

TNG462 is a MTA-cooperative PRMT5 inhibitor designed as a potentially best-in-class treatment for MTAP-deleted cancers.