[Executive Summary & Business Highlights](index=1&type=section&id=Executive%20Summary%20%26%20Business%20Highlights) This section provides an overview of the company's strategic direction, pipeline advancements, corporate developments, and upcoming key milestones [CEO Commentary](index=1&type=section&id=CEO%20Commentary) CEO Barbara Weber emphasized TNG462's potential as a best-in-class PRMT5 inhibitor for MTAP-del cancers, with efficacy data expected this year to inform a registrational study and ongoing combination trials - **TNG462** is considered a potentially **best-in-class PRMT5 inhibitor** for MTAP-del pancreatic and lung cancers[2](index=2&type=chunk) - Efficacy and tolerability data from the **TNG462 monotherapy Phase 1/2 study** are expected **later this year**, which will guide the initiation of a registrational study in pancreatic cancer next year and development strategy for lung cancer[2](index=2&type=chunk) - Enrollment is ongoing for the **TNG462 combination clinical trial** with Revolution Medicines' RAS(ON) inhibitors, with promising preclinical data supporting its potential for RAS-mut, MTAP-del cancers[2](index=2&type=chunk) [Pipeline Update](index=1&type=section&id=Pipeline%20Update) Tango Therapeutics updated on key pipeline candidates TNG462, TNG456, and TNG260, detailing trial progress, data expectations, and proof-of-mechanism [TNG462](index=1&type=section&id=TNG462) This section details the clinical progress of TNG462, including its combination trial initiation, expected monotherapy data, and favorable tolerability profile - **First patient treated in June** in a combination trial (NCT06922591) with Revolution Medicines' RAS(ON) inhibitors (daraxonrasib and zoldonrasib)[3](index=3&type=chunk) - Clinical data update on the **TNG462 Phase 1/2 monotherapy trial** is expected in the **second half of 2025**[3](index=3&type=chunk) - TNG462 continues to be very well-tolerated at **250mg once-daily (QD)** and below, consistent with a **best-in-class profile**[3](index=3&type=chunk) [TNG456](index=2&type=section&id=TNG456) This section outlines the initiation of the Phase 1/2 clinical trial for TNG456, focusing on its evaluation in glioblastoma - **First patient treated in May** with TNG456 in the dose escalation portion of the Phase 1/2 clinical trial (NCT06810544)[4](index=4&type=chunk) - The trial focuses on glioblastoma and is evaluating safety, pharmacokinetics, pharmacodynamics, and antitumor activity as a monotherapy[4](index=4&type=chunk) [TNG260](index=2&type=section&id=TNG260) This section highlights the establishment of TNG260's proof-of-mechanism and its ongoing dose expansion cohort in STK11-mut/RAS WT lung cancer - Proof-of-mechanism established based on pharmacodynamic data from on-treatment patient biopsies, showing favorable safety, tolerability, and pharmacokinetic profiles at the **80 mg QD expansion dose**[7](index=7&type=chunk) - The dose expansion cohort of the TNG260 Phase 1/2 trial is ongoing in STK11-mut/RAS WT lung cancer, evaluating TNG260 in combination with pembrolizumab[7](index=7&type=chunk) - The Company plans to present **TNG260 clinical data** in the **second half of 2025**[7](index=7&type=chunk) [Corporate Development](index=2&type=section&id=Corporate%20Development) Tango and Gilead mutually shortened their research collaboration term to five years, ending August 4, 2025, with no financial penalty, preserving all licensed programs, milestones, and royalties - Research term of collaboration and license agreement with Gilead truncated from **seven to five years**, concluding on **August 4, 2025**[6](index=6&type=chunk) - No financial penalty to Tango, no licensed programs returned, ongoing work at Gilead continues, and future milestones/royalties agreements remain in effect[6](index=6&type=chunk) - Remaining unrecognized deferred revenue of **$53.8 million** as of June 30, 2025, will be recognized in the **third quarter of 2025**[6](index=6&type=chunk) [Upcoming Milestones](index=2&type=section&id=Upcoming%20Milestones) Tango Therapeutics anticipates two key clinical data updates in the second half of 2025: one for TNG462 monotherapy Phase 1/2 clinical data and another for TNG260 clinical data - **TNG462 monotherapy Phase 1/2 clinical data update** expected in **2H 2025**[8](index=8&type=chunk) - **TNG260 clinical data** expected in **2H 2025**[8](index=8&type=chunk) [Financial Results (Q2 2025)](index=2&type=section&id=Financial%20Results%20(Q2%202025)) This section presents Tango Therapeutics' financial performance for the second quarter of 2025, covering cash position, revenue, operating expenses, and net loss [Cash Position](index=2&type=section&id=Cash%20Position) As of June 30, 2025, Tango Therapeutics held $180.8 million in cash, cash equivalents, and marketable securities, which is projected to fund operations into the first quarter of 2027 Cash, Cash Equivalents and Marketable Securities | As of Date | Amount (in millions USD) | | :------------ | :----------------------- | | June 30, 2025 | **$180.8** | - Expected to fund operations into the **first quarter of 2027**[7](index=7&type=chunk) [Revenue Analysis](index=2&type=section&id=Revenue%20Analysis) Tango Therapeutics experienced a significant decrease in total revenue for Q2 2025 and the six months ended June 30, 2025, primarily due to lower collaboration revenue and the absence of a one-time license revenue event that occurred in Q2 2024 Revenue Comparison (Q2 2025 vs. Q2 2024) | Revenue Type | Q2 2025 (in thousands USD) | Q2 2024 (in thousands USD) | Change (YoY) | | :-------------- | :------------------------- | :------------------------- | :----------- | | Collaboration | **$3,181** | **$7,775** | **-$4,594** | | License | **$0** | **$12,100** | **-$12,100** | | **Total Revenue** | **$3,181** | **$19,875** | **-$16,694** | Revenue Comparison (Six Months Ended June 30, 2025 vs. 2024) | Revenue Type | 6M 2025 (in thousands USD) | 6M 2024 (in thousands USD) | Change (YoY) | | :-------------- | :------------------------- | :------------------------- | :----------- | | Collaboration | **$8,573** | **$14,246** | **-$5,673** | | License | **$0** | **$12,100** | **-$12,100** | | **Total Revenue** | **$8,573** | **$26,346** | **-$17,773** | - Decrease in license revenue is primarily due to licensing a drug discovery program to Gilead for **$12.0 million** during the second quarter of 2024, which did not recur in 2025[10](index=10&type=chunk) [Operating Expenses](index=3&type=section&id=Operating%20Expenses) Research and development expenses decreased due to reduced spending on discontinued clinical programs and lower TNG260 and discovery program expenses, partially offset by increased investment in TNG462, TNG456, and TNG961. General and administrative expenses saw a slight increase, mainly due to higher personnel, facilities, and IT-related costs Operating Expenses Comparison (Q2 2025 vs. Q2 2024) | Expense Type | Q2 2025 (in thousands USD) | Q2 2024 (in thousands USD) | Change (YoY) | | :--------------------------- | :------------------------- | :------------------------- | :----------- | | Research and development | **$32,807** | **$38,654** | **-$5,847** | | General and administrative | **$11,341** | **$10,773** | **+$568** | | **Total Operating Expenses** | **$44,148** | **$49,427** | **-$5,279** | Operating Expenses Comparison (Six Months Ended June 30, 2025 vs. 2024) | Expense Type | 6M 2025 (in thousands USD) | 6M 2024 (in thousands USD) | Change (YoY) | | :--------------------------- | :------------------------- | :------------------------- | :----------- | | Research and development | **$69,249** | **$76,719** | **-$7,470** | | General and administrative | **$22,821** | **$21,434** | **+$1,387** | | **Total Operating Expenses** | **$92,070** | **$98,153** | **-$6,083** | - R&D decrease due to lower spend on discontinued clinical programs (TNG908 and TNG348) and reduced TNG260 and discovery program expenses, partially offset by increased spend for TNG462, TNG456, and TNG961[11](index=11&type=chunk) [Net Loss and EPS](index=3&type=section&id=Net%20Loss%20and%20EPS) Tango Therapeutics reported an increased net loss for

Core Insights - Tango Therapeutics has initiated clinical trials for TNG462 and TNG456, focusing on precision cancer therapies for pancreatic and lung cancers, as well as glioblastoma [1][2][4] Pipeline Update - TNG462 is positioned as a best-in-class PRMT5 inhibitor targeting MTAP-deleted pancreatic and lung cancers, with data expected to support its efficacy later this year [2][3] - TNG456 is currently in a Phase 1/2 trial for glioblastoma, with the first patient treated in May 2025 [4] - TNG260, a CoREST complex inhibitor, is also in development, with clinical data expected in the second half of 2025 [8] Corporate Development Update - The collaboration with Gilead has been shortened from seven to five years, with no financial penalties for Tango, and a deferred revenue balance of $53.8 million will be recognized in Q3 2025 [9] - Tango Therapeutics held $180.8 million in cash and equivalents as of June 30, 2025, expected to fund operations into Q1 2027 [10] Financial Results - Collaboration revenue decreased to $3.2 million for Q2 2025 from $7.8 million in Q2 2024, and for the six months ended June 30, 2025, it was $8.6 million compared to $14.2 million in the same period in 2024 [11] - License revenue was absent in Q2 2025, down from $12.1 million in Q2 2024, primarily due to a prior licensing agreement with Gilead [12] - Research and development expenses were $32.8 million for Q2 2025, down from $38.7 million in Q2 2024, attributed to reduced spending on discontinued programs [13] - General and administrative expenses increased to $11.3 million for Q2 2025 from $10.8 million in Q2 2024, mainly due to higher personnel and IT costs [14] - The net loss for Q2 2025 was $38.9 million, or $0.35 per share, compared to a net loss of $25.6 million, or $0.24 per share, in Q2 2024 [15] Upcoming Milestones - Clinical data updates for TNG462 and TNG260 are anticipated in the second half of 2025 [18]

Group 1 - Tango Therapeutics, Inc. (TNGX) shares have increased by 18.7% over the past four weeks, closing at $6.46, with a mean price target of $10.43 indicating a potential upside of 61.5% [1] - The mean estimate consists of seven short-term price targets with a standard deviation of $2.23, where the lowest estimate is $8.00 (23.8% increase) and the highest is $13.00 (101.2% increase) [2] - Analysts show strong agreement on TNGX's ability to report better earnings than previously predicted, which supports the view of potential upside [4][11] Group 2 - The Zacks Consensus Estimate for TNGX has increased by 1% due to one upward revision in earnings estimates over the last 30 days, with no negative revisions [12] - TNGX holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] - While the consensus price target may not be a reliable indicator of the extent of potential gains, it does provide a directional guide for price movement [14]

Core Viewpoint - Wall Street anticipates a year-over-year decline in earnings for Tango Therapeutics, Inc. due to lower revenues, with a focus on how actual results compare to estimates impacting stock price [1][2]. Earnings Expectations - Tango Therapeutics is expected to report a quarterly loss of $0.35 per share, reflecting a year-over-year change of -45.8% [3]. - Revenues are projected to be $6.19 million, down 68.9% from the same quarter last year [3]. Estimate Revisions - The consensus EPS estimate has been revised 1.62% higher in the last 30 days, indicating a reassessment by analysts [4]. - The Most Accurate Estimate for Tango Therapeutics is higher than the Zacks Consensus Estimate, resulting in an Earnings ESP of +0.57% [12]. Earnings Surprise Prediction - A positive Earnings ESP is a strong predictor of an earnings beat, especially when combined with a Zacks Rank of 1 (Strong Buy), 2 (Buy), or 3 (Hold) [10]. - Tango Therapeutics currently holds a Zacks Rank of 2, suggesting a likelihood of beating the consensus EPS estimate [12]. Historical Performance - In the last reported quarter, Tango Therapeutics was expected to post a loss of $0.34 per share but actually reported a loss of -$0.36, resulting in a surprise of -5.88% [13]. - Over the past four quarters, the company has beaten consensus EPS estimates two times [14]. Industry Context - Krystal Biotech, another player in the Zacks Medical - Biomedical and Genetics industry, is expected to report earnings per share of $1.08 for the same quarter, indicating a year-over-year change of +25.6% [18]. - Revenues for Krystal Biotech are expected to be $90.5 million, up 28.8% from the previous year [18].

Company Overview - Tango Therapeutics, Inc. is a clinical-stage biotechnology company focused on discovering novel drug targets and advancing precision medicine for cancer treatment [2] - The company employs the genetic principle of synthetic lethality to develop therapies targeting critical cancer-related targets [2] Financial Announcement - Tango Therapeutics will report its second quarter 2025 financial results on August 5, 2025, before the U.S. financial markets open [1] - The company has stated that it will not hold a conference call following the financial results announcement [1]

Group 1 - Tango Therapeutics, Inc. (TNGX) closed at $5.93, with a 26.4% gain over the past four weeks, and a mean price target of $10.43 indicating a 75.9% upside potential [1] - The average of seven short-term price targets ranges from $8.00 to $13.00, with a standard deviation of $2.23, suggesting a potential increase of 34.9% to 119.2% from the current price [2] - Analysts show strong agreement on TNGX's ability to report better earnings than previously predicted, which supports the view of potential upside [4][11] Group 2 - The Zacks Consensus Estimate for TNGX's current year has increased by 1% over the past month, with one estimate going higher and no negative revisions [12] - TNGX holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] - While consensus price targets may not be reliable for predicting exact gains, they can indicate the direction of price movement, which appears to be a good guide [14]

Core Insights - Tango Therapeutics has initiated the first patient dosing in a Phase 1/2 trial for TNG462 in combination with Revolution Medicines' daraxonrasib or zoldonrasib targeting MTAP-deleted and RAS mutant metastatic pancreatic or lung cancer [1][2] - The trial aims to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of TNG462 in combination with the mentioned inhibitors [2] - TNG462 is a promising MTA-cooperative PRMT5 inhibitor, with monotherapy data expected in the second half of 2025, which may inform a registrational trial for pancreatic cancer in 2026 [3] Company Overview - Tango Therapeutics is a clinical-stage biotechnology company focused on discovering novel drug targets and developing precision cancer medicines [4] - The company employs the genetic principle of synthetic lethality to create therapies targeting critical cancer-related pathways [4]

Company Overview - Tango Therapeutics, Inc. (TNGX) shares increased by 7.5% to close at $5.16, with notable trading volume compared to typical sessions, and a total gain of 157.4% over the past four weeks [1][2] Pipeline Developments - The company recently dosed the first patient in the TNG456 phase I/II study targeting MTAP-deleted solid tumors, particularly glioblastoma, which has contributed to positive market sentiment regarding its pipeline of precision cancer medicines [2] Financial Expectations - Tango Therapeutics is projected to report a quarterly loss of $0.36 per share, reflecting a year-over-year decline of 50%, with expected revenues of $5.79 million, down 70.9% from the previous year [3] - The consensus EPS estimate for the quarter has been revised slightly higher in the last 30 days, indicating a potential for price appreciation if the trend continues [4] Industry Context - Tango Therapeutics operates within the Zacks Medical - Biomedical and Genetics industry, where it holds a Zacks Rank of 3 (Hold) [5] - Another company in the same industry, Protagonist Therapeutics (PTGX), experienced a 1.1% decline in its stock price, with a monthly return of 17.5% [5][6]

Group 1 - U.S. stock futures are higher, with Dow futures gaining over 150 points [1] - Sarepta Therapeutics, Inc. shares fell 31.4% to $24.86 after suspending ELEVIDYS shipments and pausing ENVISION trial due to a second fatal liver failure in non-ambulatory Duchenne patients [1] Group 2 - KULR Technology Group, Inc. shares fell 21.9% to $0.8980 following a 1-for-8 reverse stock split [4] - Gold Royalty Corp. shares dipped 14.7% to $1.95, despite Canaccord Genuity initiating a Buy rating with a $3 price target [4] - Solid Biosciences Inc. shares fell 8% to $4.15, with JMP Securities reiterating a Market Outperform rating and maintaining a $15 price target [4] - Omada Health, Inc. shares declined 5.4% to $16.18 [4] - Repligen Corporation shares decreased 4% to $122.50 [4] - IonQ, Inc. shares slipped 3.2% to $36.65 [4] - Tango Therapeutics, Inc. shares declined 3.2% to $4.54 [4]

Summary of Tango Therapeutics Conference Call Company Overview - **Company**: Tango Therapeutics - **Industry**: Biotechnology, specifically focused on oncology and synthetic lethality Core Insights and Arguments - **Synthetic Lethality Platform**: Tango's discovery platform is based on synthetic lethality, which targets tumor suppressor gene loss that cannot be directly targeted due to their inactivation. This approach supplements existing therapies that focus on activated oncogenes [2][3] - **Pipeline Development**: Tango is advancing its lead asset, TNG-462, a PRMT5 inhibitor, which is synthetic lethal with MTAP deletions, common in lung and pancreatic cancers. The company is nearing the end of a Phase III study for this asset [8][9] - **Durability of Treatment**: The efficacy of TNG-462 is highlighted by its durability in patients, with some remaining on treatment for over a year, which is notable compared to standard chemotherapy options [10][11] - **Tolerability Profile**: TNG-462 is reported to have a best-in-class tolerability profile, making it suitable for patients with difficult-to-treat cancers [12] Pipeline Details - **TNG-462**: Focused on pancreatic and lung cancers, with plans to present data from over 20 patients in each category later this year [10] - **TNG-456**: A next-generation brain-penetrant asset aimed at glioblastoma, which has a high prevalence of MTAP deletions. This asset is expected to deliver more drug into the brain due to increased selectivity [13][15] - **TNG-260**: A coREST inhibitor targeting STK11 mutation patients, which represents a significant opportunity in non-small cell lung cancer. The program is currently in dose expansion [30][31] Competitive Landscape - **Key Competitors**: The primary competitors identified are Bristol Myers Squibb (BMS) and Amgen, with Tango believing it has a competitive edge in terms of pharmacokinetics (PK) and tolerability [21][22] - **Market Positioning**: Tango positions itself as a leader in the PRMT5 space, with a significant lead over other companies like AstraZeneca and BeiGene [22] Combination Strategies - **Combination with RAS Mutations**: Tango is initiating a study combining TNG-462 with RAS mutation-targeted therapies, which is expected to be transformative for pancreatic and lung cancer patients [27] - **Focus on Tolerability**: The company is monitoring overlapping toxicities in combination therapies but expects good tolerability based on existing safety profiles [29] Financial and Strategic Focus - **Capital Allocation**: Tango's capital allocation strategy is heavily focused on advancing the development of TNG-462 for pancreatic cancer, with plans to start a pivotal study next year [38] - **Investor Perception**: There is a belief that investors have underestimated the importance of PRMT5 as a target and Tango's position in the market. The company asserts it is well-resourced to compete effectively [36][37] Additional Insights - **Innovative Approach**: Tango's approach to synthetic lethality and its focus on specific genetic mutations (like STK11 and MTAP) are seen as innovative and potentially game-changing in oncology [30][31] - **Clinical Proof of Concept**: The company has demonstrated that its findings in animal models translate to human patients, reinforcing the validity of its therapeutic strategies [32][34]