Tango Therapeutics Presents Preclinical Data on Precision Oncology Programs at the American Association of Cancer Research 2023 Annual Meeting

Rhea-AI Summary

Tango Therapeutics (NASDAQ: TNGX) showcased key findings from its precision oncology portfolio at the AACR 2023 Annual Meeting in Orlando, Florida. Presentations included promising preclinical data for TNG908, a PRMT5 inhibitor targeting glioblastoma, which is currently in a phase 1/2 clinical trial. Additionally, TNG260 showed potential in reversing immune evasion in STK11-mutant cancers and will enter clinical trials later in 2023. The company also highlighted TNG462, another promising PRMT5 inhibitor, and TNG348, a selective USP1 inhibitor for BRCA1/2 mutant cancers, with IND submissions planned. These developments underscore Tango's commitment to targeting critical cancer pathways.

Positive

• TNG908 shows efficacy in glioblastoma in preclinical models and is selective for MTAP-null cancer cells with 15X potency.
• Phase 1/2 clinical trial for TNG908 is ongoing, targeting MTAP-deleted cancers including glioblastoma.
• TNG260 demonstrated effectiveness in reversing immune evasion caused by STK11 mutations, with clinical trials expected in H2 2023.
• TNG462 has shown deep tumor regressions in preclinical models and is set for phase 1/2 trials in mid-2023.
• TNG348 targets BRCA1 and BRCA2 mutant cancers and has shown promising results in preclinical studies.

Negative

• None.

BOSTON, April 18, 2023 (GLOBE NEWSWIRE) -- Tango Therapeutics, Inc. (NASDAQ: TNGX) today announced highlights from presentations at the American Association for Cancer Research (AACR) 2023 Annual Meeting, taking place from April 14-19, 2023 in Orlando, Florida. Tango scientists presented two oral and two poster presentations.

“At this year’s AACR Annual Meeting, we presented preclinical data from four programs across our precision oncology portfolio, including two oral presentations. The efficacy of TNG908 in glioblastoma in multiple preclinical models is highlighted in one presentation. TNG908, an MTA-cooperative PRMT5 inhibitor, is our lead program and is currently being studied in a phase 1/2 clinical trial,” said Adam Crystal, M.D., Ph.D., President of Research and Development of Tango Therapeutics. “In addition, we presented preclinical data on TNG260, a CoREST complex inhibitor demonstrating that TNG260 reverses the immune evasion caused by loss-of-function mutations in STK11 and restores sensitivity to PD-1 targeted therapy in this genetic context. It’s a tremendously exciting time for the field of precision oncology as we and others move into evaluating novel and previously not addressable targets. We are proud to be part of the scientific exchange that happens each year at AACR.”

Oral presentations

Title: TNG908, a brain-penetrant MTA-cooperative PRMT5 inhibitor, is efficacious in preclinical glioblastoma models
Abstract #: 3452
Session title: Novel Antitumor Agents and Targets
Presenter: Kimberly Briggs, Ph.D., Associate Director, Tango Therapeutics
Session Date and Time: April 17, 2023, 2:30-4:30 p.m. ET
Highlights:

• MTAP deletion occurs in 10-15% of all human cancers, including more than 40% of glioblastoma (GBM).
• TNG908 is 15X selective for MTAP-null cancer cells with the potential for broad clinical activity and a large therapeutic index.
• TNG908 is brain penetrant and is efficacious in both subcutaneous and orthotopic MTAP-null glioblastoma xenograft models.
• TNG908 is being studied in an ongoing phase 1/2 trial for patients with MTAP-deleted cancers, including GBM.

Title: TNG260: A novel, orally active, CoREST-selective deacetylase inhibitor for the treatment of STK11-mutant cancers 
Session Title: New Drugs on the Horizon Session: Part 3 
Presenter: Leanne Ahronian, Ph.D., Senior Scientist, Tango Therapeutics 
Session Date and Time: April 17, 2023, 10:15-11:45 a.m. ET 
Highlights:

• CoREST complex inhibition reverses immune evasion driven by loss of STK11 in preclinical models.
• STK11 loss-of-function mutations occur in approximately 15% of non-small cell lung, 15% of cervical, 10% of carcinoma of unknown primary, 5% of breast and 3% of pancreatic cancers.
• By inhibiting the CoREST complex, TNG260 selectively alters the expression of immunomodulatory genes in STK11 mutant cells and markedly reduces immune suppressive Treg tumor infiltration caused by anti-PD1-antibodies.
• TNG260 in combination with an anti-PD1 antibody drives strong anti-tumor efficacy in STK11-null checkpoint inhibitor resistant mouse models.
• A phase 1/2 clinical trial of TNG260 and pembrolizumab in patients with STK11 mutant cancers is expected to start in the second half of 2023.
  

Poster presentations

Title: TNG462 is a potential best-in-class MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted solid tumors
Abstract #: 4970
Session Title: Novel Targets and Pathways
Session Date and Time: April 18, 2023, 1:30-5:00 p.m. ET
Highlights:

• MTAP deletions occur in 10-15% of all human cancers, representing one of the largest opportunities for precision oncology.
• TNG462 is a potent MTA-cooperative PRMT5 inhibitor with 45X selectivity for MTAP-deleted cancer cells.
• TNG462 causes deep tumor regressions across multiple histologies in preclinical patient and cell line derived xenograft models.
• TNG462 is synergistic with multiple targeted therapeutics including KRAS, EGFR, and MAT2A inhibitors, in MTAP-deleted xenograft models.
• A phase 1/2 clinical trial evaluating TNG462 in patients with MTAP-deleted cancers, including non-small cell lung cancer, mesothelioma and cholangiocarcinoma, will be initiated in mid-2023.
  

Title: Characterization of the clinical development candidate TNG348 as a potent and selective inhibitor of USP1 for the treatment of BRCA1/2mut cancers
Abstract #: 4968
Session Title: Novel Targets and Pathways
Session Date and Time: April 18, 2023, 1:30-5:00 p.m. ET
Highlights:

• USP1 and BRCA1 are a synthetic lethal pair.
• TNG348 is a highly selective USP1 inhibitor for the treatment of BRCA1 and BRCA2 mutant and other HRD+ (homologous recombination deficient) cancers.
• USP1 inhibitors have a different mechanism of action than PARP inhibitors and are synergistic with PARP inhibitors in HRD+ preclinical models.
• HRD+ cancers, including those with BRCA1/2 mutations, include up to 50% of ovarian, 25% of breast, 10% of prostate and 5% of pancreatic cancers.
• TNG348 has single agent activity and strong PARPi synergy in multiple BRCA1/2 mutant breast and ovarian cancer mouse models as well as other BRCA1/2 wild type HRD+ models.
• USP1 and PARPi synergy is observed in both PARPi-sensitive and -resistant models suggesting the potential to improve upon the patient benefit seen with PARP inhibitors.
• An IND submission for TNG348 is planned for mid-2023.
  

Visit the “Publications and Posters” section of the Tango website to view the posters and presentations.

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. This includes expanding the universe of precision oncology targets into novel areas such as tumor suppressor gene loss and their contribution to the ability of cancer cells to evade immune cell killing. 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), 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, statements concerning the following include or constitute forward-looking statements: the Company is moving into evaluating novel and previously not addressable targets; TNG908 is 15X selective for MTAP-null cancer cells with the potential for broad clinical activity and a large therapeutic index; a phase 1/2 clinical trial of TNG260 and pembrolizumab in patients with STK11 mutant cancers, is expected to start in the second half of 2023; TNG462 is a potential best-in-class MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted solid tumors; A phase 1/2 clinical trial evaluating TNG462 in patients with MTAP-deleted cancers, including non-small cell lung cancer, mesothelioma and cholangiocarcinoma, will be initiated in mid-2023; MTAP deletions represents one of the largest opportunities for precision oncology; USP1 and PARPi synergy is observed in both PARPi-sensitive and -resistant models suggesting the potential to improve upon the patient benefit seen with PARP inhibitors; an IND submission for TNG348 is planned for mid-2023; the expected benefits of the Company's development candidates and other product candidates; and the expected timing of: (i) development candidate declaration for certain targets; (ii) initiating IND-enabling studies; (iii) filing INDs; (iv) clinical trial initiation and (v) disclosing initial and final clinical trial results. 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: Tango has limited experience conducting clinical trials (and will rely on a third party to operate its clinical trials) and may not be able to commence the clinical trial (including opening clinical trial sites and enrolling and dosing an adequate number of clinical trial participants) when expected and may not generate results (including final or initial safety, efficacy data and proof-of-mechanism) in the anticipated timeframe (or at all); the benefits of Tango pipeline products, development candidates and 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; 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; other companies may be able to develop products that are more safe and/or more effective than Tango’s product candidates; expected patient populations may not be as large as anticipated; the Company’s proprietary discovery platform is novel and may not identify any synthetic lethal targets for future development; 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; we 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 fast track designation (and such designation may not advance any anticipated approval timelines); 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 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; our products 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 third parties for conducting clinical trials and producing drug product; 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 COVID-19 pandemic. 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 fiscal year ended December 31, 2022. 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.   

Investor Contact:

Sam Martin/Andrew Vulis
Argot Partners
tango@argotpartners.com

Media Contact:

Amanda Galgay
SVP, Corporate Communications, Tango Therapeutics
media@tangotx.com

FAQ

What were the key presentations from Tango Therapeutics at AACR 2023?

Tango Therapeutics presented four programs, including preclinical data for TNG908, TNG260, TNG462, and TNG348, focusing on their efficacy in cancer treatment.

What is the status of TNG908 and its clinical trials?

TNG908 is currently in a phase 1/2 clinical trial targeting glioblastoma and other MTAP-deleted cancers.

When will the TNG260 clinical trial begin?

The clinical trial for TNG260, which targets STK11-mutant cancers, is expected to start in the second half of 2023.

What is TNG462's significance in cancer treatment?

TNG462 is highlighted as a potential best-in-class PRMT5 inhibitor for treating MTAP-deleted solid tumors and will enter clinical trials in mid-2023.

What types of cancers does TNG348 target?

TNG348 is designed to treat cancers associated with BRCA1 and BRCA2 mutations, and IND submission is planned for mid-2023.