Tango Therapeutics Inc

Previous wording

Our lead program, TNG908, is an MTA-cooperative inhibitor of PRMT5 designed to work selectively in cancer cells with an MTAP deletion. MTAP-deletion occurs in approximately 10% to 15% of all human tumors including glioblastoma, non-small cell lung cancer and pancreatic cancer. In preclinical studies, TNG908 demonstrated 15-fold greater potency in MTAP-deleted cancer cells versus normal cells and robust efficacy in vitro and in vivo. Initial pharmacodynamic (PD) data from the ongoing TNG908 Phase 1/2 study, released in May 2023, provided proof-of-mechanism of MTA-cooperative PRMT5 inhibition, demonstrated by marked reduction of SDMA staining in MTAP-deleted cancer cells versus normal tissue. Pre-treatment and on-treatment biopsies demonstrated dose-dependent decreases in tumor SDMA staining with minimal or no decrease in normal tissue. The selective inhibition of PRMT5 in MTAP-deleted cancer cells is essential to enable the therapeutic index needed for efficacy. In the second quarter of 2024, we initiated the dose expansion portion of the phase 1/2 clinical trial, opening cohorts in glioblastoma, non-small cell lung and pancreatic cancers at 600 mg twice-daily (BID). Clinical data from the ongoing trial are expected in the second half of 2024.

Current wording

Our lead program, TNG908, is an MTA-cooperative inhibitor of PRMT5 designed to work selectively in cancer cells with an MTAP deletion. MTAP-deletion occurs in approximately 10% to 15% of all human tumors including GBM, NSCLC and pancreatic cancer. In preclinical studies, TNG908 demonstrated 15-fold greater potency in MTAP-deleted cancer cells versus normal cells and robust efficacy in vitro and in vivo. Initial pharmacodynamic (PD) data from the ongoing TNG908 Phase 1/2 study, released in May 2023, provided proof-of-mechanism of MTA-cooperative PRMT5 inhibition, demonstrated by marked reduction of SDMA staining in MTAP-deleted cancer cells versus normal tissue. Pre-treatment and on-treatment biopsies demonstrated dose-dependent decreases in tumor SDMA staining with minimal or no decrease in normal tissue. The selective inhibition of PRMT5 in MTAP-deleted cancer cells is essential to enable the therapeutic index needed for efficacy. In the second quarter of 2024, we initiated the dose expansion portion of the Phase 1/2 clinical trial, opening cohorts in GBM, NSCLC and pancreatic cancer at 600 mg twice-daily (BID). Clinical data from the ongoing trial are expected in the second half of 2024.

Previous wording

Given the large number of patients with MTAP-deleted cancers who may benefit from a PRMT5 inhibitor, and the resulting potential business opportunity, we also developed a next-generation PRMT5 inhibitor, TNG462, with increased potency, MTAP deletion selectivity, as well as longer target coverage. TNG462 is 45 times more potent in cells with an MTAP deletion than those without and induces deep tumor regressions in preclinical models of multiple cancer types which is expected to significantly increase the therapeutic index. The clinical development path for TNG462 is similar to TNG908, evaluating safety and efficacy in multiple tumor types in a Phase 1/2 clinical trial. GBM is excluded from the clinical trial as TNG462 is not expected to cross the blood-brain barrier. The TNG462 IND was cleared by the FDA in the first quarter of 2023 and we announced the first patient in the Phase 1/2 clinical trial was dosed in July 2023. Patients are actively being enrolled in the dose escalation portion of the trial and to date, the safety, tolerability and pharmacokinetics profiles of TNG462 remain favorable with increasing doses. We expect to initiate the dose expansion portion of the phase 1/2 clinical trial in the second quarter of 2024. Clinical data from the ongoing trial are expected in the second half of 2024.

Current wording

Given the large number of patients with MTAP-deleted cancers who may benefit from a PRMT5 inhibitor, and the resulting potential business opportunity, we also developed a next-generation PRMT5 inhibitor, TNG462, with increased potency, MTAP deletion selectivity, as well as longer target coverage. TNG462 is 45 times more potent in cells with an MTAP deletion than those without and induces deep tumor regressions in preclinical models of multiple cancer types which is expected to significantly increase the therapeutic index. The clinical development path for TNG462 is similar to TNG908, evaluating safety and efficacy in multiple tumor types in a Phase 1/2 clinical trial. GBM is excluded from the clinical trial as TNG462 is not expected to cross the blood-brain barrier. The TNG462 investigational new drug (IND) application was cleared by the U.S. Food and Drug Administration (FDA) in the first quarter of 2023 and we announced the first patient in the Phase 1/2 clinical trial was dosed in July 2023. The dose expansion portion of the TNG462 Phase 1/2 clinical trial is ongoing. Two doses are being evaluated (200 mg QD and 300 mg QD) in non-small cell lung and pancreatic cancer, as well as a histology-agnostic cohort enriched for cholangiocarcinoma, mesothelioma, sarcoma and bladder cancers. Clinical data from the ongoing trial are expected in the second half of 2024.

Previous wording

Discovered as part of our immune evasion target discovery platform, TNG260 is a first-in-class CoREST inhibitor, which reverses the immune evasion effect of STK11 loss-of-function mutations. STK11 loss-of-function mutations are present in approximately 15% of NSCLC, 15% of cervical cancers, 10% of carcinoma of unknown primary, 5% of breast cancers and 3% of pancreatic cancers. In syngeneic models with an STK11 mutation and an intact immune system, the combination of TNG260 with an anti-PD-1 antibody resulted in sustained complete tumor regressions and the induction of immune memory against re-implantation of tumors. These preclinical data demonstrate that TNG260 in combination with an anti-PD-1 antibody is active in cancers with STK11 mutation, a setting where an anti-PD-1 antibody alone is inactive. In the first quarter of 2023, the FDA cleared the TNG260 IND and we announced the first patient in the Phase 1/2 clinical trial was dosed in July 2023. Patients are actively being enrolled in the dose escalation portion of the trial and to date, the safety, tolerability and pharmacokinetics profiles of TNG260 remain favorable. The trial is evaluating the safety, pharmacokinetics, PD and efficacy of TNG260 in combination with pembrolizumab, with a one cycle single agent run-in phase to evaluate the safety and PK of TNG260, in patients with locally advanced or metastatic solid tumors with an

Current wording

Discovered as part of our immune evasion target discovery platform, TNG260 is a first-in-class CoREST inhibitor, which reverses the immune evasion effect of STK11 loss-of-function mutations. STK11 loss-of-function mutations are present in approximately 15% of NSCLC, 15% of cervical cancers, 10% of carcinoma of unknown primary, 5% of breast cancers and 3% of pancreatic cancers. In syngeneic models with an STK11 mutation and an intact immune system, the combination of TNG260 with an anti-PD-1 antibody resulted in sustained complete tumor regressions and the induction of immune memory against re-implantation of tumors. These preclinical data demonstrate that TNG260 in combination with an anti-PD-1 antibody is active in cancers with STK11 mutation, a setting where an anti-PD-1 antibody alone is inactive. In the first quarter of 2023, the FDA cleared the TNG260 IND and we announced the first patient in the Phase 1/2 clinical trial was dosed in July 2023. The TNG260 Phase 1/2 clinical trial is ongoing, evaluating the safety, pharmacokinetics, PD and efficacy of TNG260 in combination with pembrolizumab, with a one cycle single agent run-in phase to evaluate the safety and PK of TNG260, in patients with locally advanced or metastatic solid tumors with an STK11 loss-of-function mutation. To date, the safety, tolerability and pharmacokinetics profiles are favorable. We believe that

Previous wording

STK11 loss-of-function mutation. We believe that TNG260 could be among the first oncology molecules to leverage the benefits of genetically-based patient selection (STK11-mutation) with checkpoint inhibitor therapy.

Current wording

TNG260 could be among the first oncology molecules to leverage the benefits of genetically-based patient selection (STK11-mutation) with checkpoint inhibitor therapy.

Previous wording

Since the Company's inception, we have focused primarily on organizing and staffing our company, business planning, raising capital, discovering product candidates, securing related intellectual property, and conducting research and development activities for our programs. To date, we have funded our operations primarily through equity financings and from the proceeds received from our collaboration agreement with Gilead. Since inception, we have raised an aggregate of $166.9 million of gross proceeds from the sale of our preferred shares, $342.1 million in gross proceeds through the closing of the Business Combination and simultaneous financing transactions, $225.1 million through our collaboration with Gilead and $123.0 million of gross proceeds through (i) $80.0 million from the private placement of common shares and pre-funded warrants to purchase common shares in August 2023 and (ii) $43.0 million from our "at-the-market" stock offering program in January 2024.

Current wording

Since the Company's inception, we have focused primarily on organizing and staffing our company, business planning, raising capital, discovering product candidates, securing related intellectual property, and conducting research and development activities for our programs. To date, we have funded our operations primarily through equity financings and from the proceeds received from our collaboration agreement with Gilead. Since inception, we have raised an aggregate of $166.9 million of gross proceeds from the sale of our preferred shares, $342.1 million in gross proceeds through the closing of the Business Combination and simultaneous financing transactions, $237.1 million through our collaboration with Gilead and $123.0 million of gross proceeds through (i) $80.0 million from the private placement of common shares and pre-funded warrants to purchase common shares in August 2023 and (ii) $43.0 million from our "at-the-market" stock offering program.

Previous wording

We expect that our existing cash, cash equivalents and marketable securities on hand as of March 31, 2024 of $343.6 million will enable us to fund our operating expenses and capital expenditure requirements at least into late 2026. Since inception, we have incurred significant operating losses. For the three months ended March 31, 2024 and 2023, our net losses were $37.9 million and $28.0 million, respectively. We had an accumulated deficit of $409.2 million as of March 31, 2024. We expect to continue to incur significant and increasing expenses and operating losses for the foreseeable future, as we advance our product candidates through preclinical and clinical development and seek regulatory approvals, manufacture drug product and drug supply, and maintain and expand our intellectual property portfolio. We also expect to hire additional personnel, pay for accounting, audit, legal, regulatory and consulting services, and pay costs associated with maintaining compliance with Nasdaq listing rules and the requirements of the U.S. Securities and Exchange Commission, director and officer liability insurance, investor and public relations activities and other expenses associated with operating as a public company. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our preclinical studies, our clinical trials, and our expenditures on other research and development activities.

Current wording

We expect that our existing cash, cash equivalents and marketable securities on hand as of June 30, 2024 of $322.1 million will enable us to fund our operating expenses and capital expenditure requirements at least into 2027. Since inception, we have incurred significant operating losses. For the six months ended June 30, 2024 and 2023, our net losses were $63.5 million and $48.7 million, respectively. We had an accumulated deficit of $434.7 million as of June 30, 2024. We expect to continue to incur significant and increasing expenses and operating losses for the foreseeable future, as we advance our product candidates through preclinical and clinical development and seek regulatory approvals, manufacture drug product and drug supply, and maintain and expand our intellectual property portfolio. We also expect to hire additional personnel, pay for accounting, audit, legal, regulatory and consulting services, and pay costs associated with maintaining compliance with Nasdaq listing rules and the requirements of the U.S. Securities and Exchange Commission, director and officer liability insurance, investor and public relations activities and other expenses associated with operating as a public company. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our preclinical studies, our clinical trials, and our expenditures on other research and development activities.

Previous wording

In September 2022, we entered into a sales agreement (the Sales Agreement) with Jefferies LLC (Jefferies) which permitted the Company to sell from time to time, at its option, up to an aggregate of $100.0 million of shares of its common stock through Jefferies, as sales agent. Sales of the common stock, if any, will be made by methods deemed to be "at-the-market" stock offerings. The Sales Agreement will terminate upon the earliest of: (a) the sale of $100.0 million of shares of the Company's common stock or (b) the termination of the Sales Agreement by the Company or Jefferies.

Current wording

In September 2022, we entered into a sales agreement (the Sales Agreement) with Jefferies LLC (Jefferies), which permits us to sell from time to time, at our option, up to an aggregate of $100.0 million of shares of common stock through Jefferies, as sales agent. Sales of the common stock, if any, will be made by methods deemed to be "at-the-market" stock offerings. The Sales Agreement will terminate upon the earliest of: (a) the sale of $100.0 million of shares of our common stock or (b) the termination of the Sales Agreement by us or Jefferies.

Previous wording

In October 2018, we entered into a collaboration agreement with Gilead (2018 Gilead Agreement). Pursuant to the terms of the 2018 Gilead Agreement, we received an initial upfront payment of $50.0 million. The upfront payment was initially recorded as deferred revenue on our balance sheet and is recognized as revenue as or when the performance obligation under the contract is satisfied. In August 2020, the 2018 Gilead Agreement was expanded into a broader collaboration via an amended and restated research collaboration and license agreement (Gilead Agreement). Pursuant to the terms of the Gilead Agreement, we received an upfront payment of $125.0 million. Consistent with the treatment of the previously received upfront payment, this upfront payment was recorded as deferred revenue on our balance sheet and is recognized as revenue as or when the performance obligation under the contract is satisfied. In 2020 and 2021, Gilead elected to extend two programs for research extension fees totaling $24.0 million, which was added to our estimate of the transaction price to total $199.0 million.

Current wording

In October 2018, we entered into a collaboration agreement (the 2018 Gilead Agreement) with Gilead Sciences, Inc. (Gilead). Pursuant to the terms of the 2018 Gilead Agreement, we received an initial upfront payment of $50.0 million. The upfront payment was initially recorded as deferred revenue on our balance sheet and is recognized as revenue as or when the performance obligation under the contract is satisfied. In August 2020, the 2018 Gilead Agreement was expanded into a broader collaboration via an amended and restated research collaboration and license agreement (the Gilead Agreement). Pursuant to the terms of the Gilead Agreement, we received an upfront payment of $125.0 million. Consistent with the treatment of the previously received upfront payment, this upfront payment was recorded as deferred revenue on our balance sheet and is recognized as revenue as or when the performance obligation under the contract is satisfied. In 2020 and 2021, Gilead elected to extend two programs for research extension fees totaling $24.0 million, which was added to our estimate of the transaction price to total $199.0 million. In June 2024, Gilead licensed a program for a $12.0 million fee, which was recognized as license revenue in the second quarter of 2024.

Previous wording

As of March 31, 2024, $113.1 million has been recognized as collaboration revenue related to the upfront and research option-extension payments from the Gilead agreements.

Current wording

As of June 30, 2024, $120.9 million has been recognized as collaboration revenue related to the upfront and research option-extension payments from the Gilead Agreement and the 2018 Gilead Agreement (the Gilead Agreements).

Previous wording

During the three months ended March 31, 2024 and 2023, we recognized $6.5 million and $5.8 million, respectively, of collaboration revenue associated with the Gilead agreements based on performance completed during each period.

Current wording

During the three months ended June 30, 2024 and 2023, we recognized $7.8 million and $9.6 million, respectively, and during the six months ended June 30, 2024 and 2023, we recognized $14.2 million and $15.4 million, respectively, of collaboration revenue associated with the Gilead Agreements based on performance completed during each period.

Previous wording

Our provision for income tax consists of an estimate for U.S. federal and state income taxes based on enacted rates, as adjusted for allowable credits, deductions, uncertain tax positions, changes in deferred tax assets and liabilities and changes in tax law. We recorded an insignificant provision for income taxes for each of the three month periods ended March 31, 2024 and 2023.

Current wording

Our provision for income tax consists of an estimate for U.S. federal and state income taxes based on enacted rates, as adjusted for allowable credits, deductions, uncertain tax positions, changes in deferred tax assets and liabilities and changes in tax law. We recorded an insignificant provision for income taxes for each of the three and six months ended June 30, 2024 and 2023.

Previous wording

Collaboration revenue of $6.5 million and $5.8 million for the three months ended March 31, 2024 and 2023, respectively, was derived from the Gilead collaboration. Research costs incurred under the collaboration were similar during each of the three month periods presented which resulted in similar collaboration revenue amounts recognized.

Current wording

Collaboration revenue of $7.8 million and $9.6 million for the three months ended June 30, 2024 and 2023, respectively, was derived from the Gilead collaboration. Research costs incurred under the collaboration were lower during the three months ended June 30, 2024, which resulted in lower collaboration revenue amounts recognized.

Previous wording

Research and development expense was $38.1 million for the three months ended March 31, 2024 compared to $28.0 million for the three months ended March 31, 2023. The increase was primarily due to a $6.4 million increase relating to the advancement of our clinical programs. Additionally, the increase was also due to $3.8 million in personnel-related costs, including share-based compensation expense and additional headcount to support our research and development activities.

Current wording

Research and development expense was $38.7 million for the three months ended June 30, 2024 compared to $28.7 million for the three months ended June 30, 2023. The increase of $10.0 million was primarily due to a $5.6 million increase relating to the advancement of our clinical and preclinical programs. Additionally, the increase was also due to $3.3 million in personnel-related costs, including share-based compensation expense and additional headcount to support our research and development activities.

Previous wording

Interest income was $2.2 million for the three months ended March 31, 2024 compared to $1.0 million for the three months ended March 31, 2023, with the increase attributed to an increase in interest rates in 2024 as compared to 2023.

Current wording

Interest income was $2.1 million for the three months ended June 30, 2024 compared to $1.5 million for the three months ended June 30, 2023, with the increase attributed to an increase in interest rates in 2024 as compared to 2023.

Previous wording

Other income, net was $2.2 million for the three months ended March 31, 2024 compared to other income, net of $1.2 million for the three months ended March 31, 2023, with the increase attributed to accretion on investments purchased at a discount.

Current wording

Other income, net was $2.0 million for the three months ended June 30, 2024 compared to other income, net of $1.2 million for the three months ended June 30, 2023, with the increase attributed to accretion on investments purchased at a discount.

Previous wording

Provision for income taxes was less than $0.1 million for the three months ended March 31, 2024 and $0 for the three months ended March 31, 2023. The income tax provision amount for the period ended March 31, 2024 is primarily attributable to state taxes on interest income earned on marketable securities.

Current wording

Provision for income taxes was $0.1 million for the three months ended June 30, 2024 and $0.1 million for the three months ended June 30, 2023. The income tax provision amount for the period ended June 30, 2024 is primarily attributable to state taxes on interest income earned on marketable securities.

Previous wording

Since our inception, we have generated recurring net losses. We have not yet commercialized any product and we do not expect to generate revenue from sales of any products for several years, if at all. To date, we have funded our operations primarily through equity financings and from the proceeds received from our collaboration agreement with Gilead. Since inception, we have raised an aggregate of $166.9 million of gross proceeds from the sale of our preferred shares, $342.1 million in gross proceeds from the Business Combination and simultaneous financing transactions, $123.0 million of gross proceeds through the $80.0 million private placement of common shares and pre-funded warrants to purchase common shares in August 2023, as well as $43.0 million of gross proceeds from our "at-the-market" stock offering program in January 2024, and another $225.1 million through our collaboration with Gilead. As of March 31, 2024, we had cash and cash equivalents and marketable securities of $343.6 million.

Current wording

Since our inception, we have generated recurring net losses. We have not yet commercialized any product and we do not expect to generate revenue from sales of any products for several years, if at all. To date, we have funded our operations primarily through equity financings and from the proceeds received from our collaboration agreement with Gilead. Since inception, we have raised an aggregate of $166.9 million of gross proceeds from the sale of our preferred shares, $342.1 million in gross proceeds from the Business Combination and simultaneous financing transactions, $123.0 million of gross proceeds through (i) the $80.0 million private placement of common shares and pre-funded warrants to purchase common shares in August 2023 and (ii) the $43.0 million from our "at-the-market" stock offering program, and another $237.1 million through our collaboration with Gilead. As of June 30, 2024, we had cash and cash equivalents and marketable securities of $322.1 million.

Previous wording

We expect that our existing cash, cash equivalents and marketable securities on hand as of March 31, 2024 of $343.6 million will enable us to fund our operating expenses and capital expenditure requirements at least into late 2026. We have based this estimate on assumptions that may prove to be wrong, and we could expend our capital resources sooner than we expect.

Current wording

We expect that our existing cash, cash equivalents and marketable securities on hand as of June 30, 2024 of $322.1 million will enable us to fund our operating expenses and capital expenditure requirements at least into 2027. We have based this estimate on assumptions that may prove to be wrong, and we could expend our capital resources sooner than we expect.

Previous wording

The following table summarizes our cash flows for each of the three month periods presented:

Current wording

The following table summarizes our cash flows for each of the six month periods presented:

Previous wording

Net cash used in operating activities was $37.9 million for the three months ended March 31, 2024 compared to net cash used in operating activities of $34.9 million for the three months ended March 31, 2023. The increase in net cash used in operating activities for the three months ended March 31, 2024 was primarily due to an increase to the net loss as a direct result of higher operating expenses related to the advancement of our programs and personnel-related costs. The increase was partially offset by changes in operating assets and liabilities and higher non-cash expenses, including stock compensation.

Current wording

Net cash used in operating activities was $61.5 million for the six months ended June 30, 2024 compared to net cash used in operating activities of $59.4 million for the six months ended June 30, 2023. The increase in net cash used in operating activities for the six months ended June 30, 2024 was primarily due to an increase to the net loss as a result of higher operating expenses related to the advancement of our programs and personnel-related costs. The increase was partially offset by changes in operating assets and liabilities and higher non-cash expenses, including stock compensation.

Previous wording

Net cash used in investing activities was $11.2 million for the three months ended March 31, 2024 compared to net cash provided by investing activities of $31.5 million for the three months ended March 31, 2023. The change was primarily due to an increase in purchases of marketable securities as compared to the three months ended March 31, 2023, which was partially offset by an increase in sales and maturities of marketable securities as compared to the three months ended March 31, 2023.

Current wording

Net cash provided by investing activities was $1.5 million for the six months ended June 30, 2024 compared to net cash provided by investing activities of $64.2 million for the six months ended June 30, 2023. The change was primarily due to an increase in purchases of marketable securities as compared to the three months ended June 30, 2023, which was partially offset by an increase in sales and maturities of marketable securities as compared to the three months ended June 30, 2023.

Previous wording

Net cash provided by financing activities was $43.0 million for the three months ended March 31, 2024 compared to net cash provided by financing activities of $0.1 million for the three months ended March 31, 2023. The cash provided by financing activities for three months ended March 31, 2024 consisted of the $41.7 million in net proceeds received from our "at-the-market" stock offering program in January 2024, as well as the cash provided from the exercises of stock options. The cash provided by financing activities for the three months ended March 31, 2023 was the result of cash provided from the exercises of stock options.

Current wording

Net cash provided by financing activities was $44.3 million for the six months ended June 30, 2024 compared to net cash provided by financing activities of $0.7 million for the six months ended June 30, 2023. The cash provided by financing activities for six months ended June 30, 2024 consisted of the $41.7 million in net proceeds received from our "at-the-market" stock offering program in January 2024, as well as the cash provided from the exercises of stock options and ESPP purchases. The cash provided by financing activities for the three months ended June 30, 2023 was the result of cash provided from the exercises of stock options and ESPP purchases.

Previous wording

Under ASC 606, we will recognize revenue when we fulfill our performance obligations under the agreement with Gilead. As the required performance obligation is satisfied, we will recognize revenue for the portion satisfied and record a receivable for any fees that have not been received. Amounts are recorded as short-term collaboration receivables when our right to consideration is unconditional. A contract liability is recognized when a customer prepays consideration or owes payment to an entity in advance of our performance according to a contract. We do not assess whether a contract has a significant financing component if the expectation at contract inception is that the period between payment by the customer and the transfer of the promised goods or services to the customer will be one year or less. We expense incremental costs of obtaining a contract as and when incurred if the expected amortization period of the asset that we would have recognized is one year or less or the amount is immaterial.

Current wording

Under ASC 606, we will recognize revenue when we fulfill our performance obligations under the agreements with customers. As the required performance obligation is satisfied, we will recognize revenue for the portion satisfied and record a receivable for any fees that have not been received. Amounts are recorded as short-term collaboration receivables when our right to consideration is unconditional. A contract liability is recognized when a customer prepays consideration or owes payment to an entity in advance of our performance according to a contract. We do not assess whether a contract has a significant financing component if the expectation at contract inception is that the period between payment by the customer and the transfer of the promised goods or services to the customer will be one year or less. We expense incremental costs of obtaining a contract as and when incurred if the expected amortization period of the asset that we would have recognized is one year or less or the amount is immaterial.