Tango Therapeutics Inc

Previous wording

We are a precision oncology company with a limited operating history. Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of risk. Since the Company's inception, we have devoted substantially all of our efforts to organizing and staffing our company, acquiring and developing intellectual property, business planning, raising capital, conducting discovery, research and development activities (including conducting clinical trials), and providing general and administrative support for these operations. We have no products approved for commercial sale and therefore have never generated any revenue from product sales, and we do not expect to in the foreseeable future. The revenue that we have generated from our collaboration agreement is also not sufficient to fund our operations. We have not obtained regulatory approvals for any of our product candidates, and there is no assurance that we will obtain approvals in the future. We have four investigational new drug, or IND, applications that have been cleared by the FDA for the following compounds: TNG908, TNG462, TNG260 and TNG348. Our other product candidates are still in preclinical development. We expect to continue to incur significant expenses and operating losses over the next several years and for the foreseeable future. Our prior losses, combined with expected future losses, have had and will continue to have an adverse effect on cash and cash equivalent holdings, our stockholders’ equity and working capital. If we were to expend our cash resources more quickly than we anticipate as we advance into and through the regulatory approval process, our cash runway may be shorter than the target we may disclose from time to time.

Current wording

We are a precision oncology company with a limited operating history. Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of risk. Since the Company's inception, we have devoted substantially all of our efforts to organizing and staffing our company, acquiring and developing intellectual property, business planning, raising capital, conducting discovery, research and development activities (including conducting clinical trials), and providing general and administrative support for these operations. We have no products approved for commercial sale and therefore have never generated any revenue from product sales, and we do not expect to in the foreseeable future. The revenue that we have generated from our collaboration agreement is also not sufficient to fund our operations. We have not obtained regulatory approvals to market and sell any of our product candidates, and there is no assurance that we will obtain approvals in the future. The FDA has cleared five of our IND applications (TNG908, TNG462, TNG260, TNG348 and TNG456); however, we have since discontinued development of TNG908 and TNG348. Our other product candidates are still in preclinical development. We expect to continue to incur significant expenses and operating losses over the next several years and for the foreseeable future. Our prior losses, combined with expected future losses, have had and will continue to have an adverse effect on cash and cash equivalent holdings, accumulated deficit, stockholders’ equity and working capital. If we were to expend our cash resources more quickly than we anticipate as we advance into and through the regulatory approval process for our product candidates, our cash runway may be shorter than the target we may disclose from time to time.

Previous wording

We have incurred significant net losses since our inception. As of December 31, 2023, we had an accumulated deficit of $371.3 million. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect our research and development expenses to increase significantly in connection with the continuation of clinical trials of our product candidates. In addition, if we obtain regulatory approval for our product candidates, we will incur significant sales, marketing and manufacturing expenses. As a result, we expect to continue to incur significant and increasing operating losses for the foreseeable future. Because of the numerous risks and uncertainties associated with developing pharmaceutical products, we are unable to predict the extent of any future losses or when we will become profitable, if at all. Even if we do become profitable, we may not be able to sustain or increase our profitability on a quarterly or annual basis.

Current wording

We have incurred significant net losses since our inception. As of December 31, 2024, we had an accumulated deficit of $501.6 million. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect our research and development expenses to increase significantly in connection with the continuation of clinical trials of our product candidates. In addition, if we obtain regulatory approval for our product candidates, we will incur significant sales, marketing and manufacturing expenses. As a result, we expect to continue to incur significant and increasing operating losses for the foreseeable future. Because of the numerous risks and uncertainties associated with developing pharmaceutical products, we are unable to predict the extent of any future losses or when we will become profitable, if at all. Even if we do become profitable, we may not be able to sustain or increase our profitability on a quarterly or annual basis.

Previous wording

the timing and success or failure of on-going and future clinical trials for our product candidates or competing product candidates, or any other change in the competitive landscape of our industry, including consolidation among our competitors or partners (such as the acquisition of Mirati Therapeutics by Bristol Myers Squibb);

Current wording

the timing and success or failure of ongoing and future clinical trials for our product candidates or competing product candidates, or any other change in the competitive landscape of our industry, including consolidation among our competitors or partners (such as the acquisition of Mirati by Bristol Myers Squibb in January 2024);

Previous wording

our ability to obtain INDs for our pipeline product candidates, successfully open clinical trial sites and recruit and retain subjects for clinical trials, and any delays caused by difficulties in connection with such efforts;

Current wording

our ability to obtain INDs for our pipeline product candidates, successfully open clinical trial sites and recruit and retain subjects for clinical trials (including combination trials), and any delays caused by difficulties in connection with such efforts;

Previous wording

the level of demand for our product candidates should they receive regulatory approval, which demand may vary significantly;

Current wording

the level of demand for our product candidates (should they receive regulatory approval), which may vary significantly from our expectations;

Previous wording

the changing and volatile U.S. and global economic environments, including as a result of the efforts to reduce spending on healthcare; and

Current wording

the changing and volatile U.S. and global economic environments, including as a result of the efforts to reduce spending on healthcare generally and pharmaceuticals in particular; and

Previous wording

As a result, comparing our operating results on a period-to-period basis may not be meaningful. This variability and unpredictability could also result in our failing to meet the expectations of industry or financial analysts or investors for any period. If our revenue or operating results fall below the expectations of analysts or investors or below any forecasts we may provide to the market, or if the forecasts we provide to the market are below the expectations of analysts or investors, the price of our common stock could decline substantially. Such a stock price decline could occur even when we have met any previously publicly stated financial or operational guidance we may provide.

Current wording

As a result, comparing our operating results on a period-to-period basis may not be meaningful. This variability and unpredictability could also result in our failing to meet the expectations of industry or financial analysts or investors for any period. If our clinical data, revenue or operating results fail to meet the expectations of analysts or investors or below any forecasts we may provide to the market, or if the forecasts we provide to the market are below the expectations of analysts or investors, the price of our common stock could decline substantially. Such a stock price decline could occur even when we have met any previously publicly stated financial or operational guidance we may provide.

Previous wording

timely complete patient enrollment and patient dosing in our four clinical trials (TNG908, TNG462, TNG260 and TNG348);

Current wording

timely complete patient enrollment and patient dosing in our current and future clinical trials (including our current trials of TNG462 and TNG260 and planned clinical trials, including combination clinical trials, with TNG462 and TNG456);

Previous wording

successfully complete our ongoing clinical trials and any future clinical trials we may initiate;

Current wording

successfully complete our ongoing clinical trials and any future clinical trials we may initiate (including combination clinical trials);

Previous wording

initiate and successfully complete all safety and efficacy studies required to obtain U.S. and foreign regulatory approval for the sale our product candidates and obtain approval of our products by regulatory authorities;

Current wording

initiate and successfully complete all safety and efficacy studies required to obtain U.S. and foreign regulatory approval for the sale of our product candidates and obtain approval of our products by regulatory authorities;

Previous wording

obtain and maintain patent and trade secret protection or regulatory exclusivity for our product candidates;

Current wording

obtain and maintain patent and/or trade secret protection or regulatory exclusivity for our product candidates;

Previous wording

The development of pharmaceutical products is capital-intensive. We are currently advancing our precision oncology programs through clinical and preclinical development. We received FDA clearance of our four IND applications in 2022 and 2023. We are actively enrolling patients in each of these four Phase 1/2 clinical trials, each of which is evaluating safety and efficacy in multiple indications. We expect our expenses to significantly increase as we continue to advance and complete clinical trials, and seek regulatory approval for, our product candidates. Further, we continue our research efforts to identify and advance additional precision oncology compounds that may benefit patients. Even though we completed an $80 million private placement in August 2023 and received $41.7 million in net proceeds from our "at-the-market" stock offering program in January 2024, we will still be required to raise substantial additional funding in the future in order to continue to fund our operations and advance our clinical trial programs.

Current wording

The development of pharmaceutical products is capital-intensive. We are currently advancing our precision oncology programs through clinical and preclinical development. We are actively enrolling patients in two Phase 1/2 clinical trials, each of which is evaluating safety and efficacy in multiple indications (and we expect to begin enrollment in the TNG456 Phase 1/2 clinical trial in the first half of 2025). We expect our expenses to significantly increase as we continue to advance and complete clinical trials (including multiple combination clinical trials), and seek regulatory approval for, our product candidates, including in combination with other therapeutics. Further, we continue our research efforts to identify and advance additional precision oncology compounds that may benefit patients. Even though we completed an $80 million private placement in August 2023 and received $41.7 million in net proceeds from our "at-the-market" stock offering program in January 2024, we will still be required to raise substantial additional funding in the future in order to continue to fund our operations and advance our clinical trial programs.

Previous wording

We believe that our existing cash, cash equivalents and marketable securities on hand as of December 31, 2023, in addition to $41.7 million in net proceeds from our "at-the-market" stock offering program in January 2024, will enable us to fund our operating expenses and capital expenditure requirements at least into late 2026. However, our future capital requirements will depend on and could increase significantly as a result of many factors (which may result in exhausting such cash resources prior to late 2026), including:

Current wording

We believe that our existing cash, cash equivalents and marketable securities on hand as of December 31, 2024 will enable us to fund our operating expenses and capital expenditure requirements at least into the third quarter of 2026. However, our future capital requirements will depend on and could increase significantly as a result of many factors (which may result in exhausting such cash resources prior to the third quarter of 2026), including:

Previous wording

the scope, progress, results and costs of product discovery, preclinical and clinical development, and clinical trials for our product candidates;

Current wording

the scope, progress, results and costs of product discovery, preclinical and clinical development, and clinical trials for our product candidates, including recruiting patients for and conducting multiple planned clinical trials;

Previous wording

the cost of acquiring therapies to be used in combination clinical trials (such as pembrolizumab, an anti-PD-1 antibody that is used in combination with TNG260; and olaparib, a PARP inhibitor, that is used in combination with TNG348 in the Phase 1/2 clinical trials);

Current wording

the cost of acquiring therapies to be used in combination clinical trials (such as pembrolizumab, an anti-PD-1 antibody that is used in combination with TNG260);

Previous wording

As a result of disruptions in the financial markets in general, and the recent decrease in biopharmaceutical stock prices and market capitalizations in particular, equity and debt financing may be more difficult to obtain and may have a material adverse effect on our ability to meet our fundraising needs. We cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us, if at all.

Current wording

As a result of disruptions in the financial markets in general, and the challenges facing biopharmaceutical stock prices and market capitalizations in recent years in particular, equity and debt financing may be more difficult to obtain and may have a material adverse effect on our ability to meet our fundraising needs. We cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us, if at all.

Previous wording

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through one or a combination of private and public equity offerings (such as the private placement of our common stock in August 2023 and sales of common stock under an "at-the-market" stock offering program), debt financings, collaborations, strategic alliances and licensing arrangements. We do not have any committed external source of funds. The terms of any financing may adversely affect the holdings or the rights of our stockholders and the issuance of additional securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our shares to decline. To the extent that we raise additional capital through the sale of common stock or securities convertible or exchangeable into common stock, the ownership interest of our existing common stockholders will be diluted, and the terms of those securities may include liquidation or other preferences that may materially adversely affect your rights as a common stockholder. Debt financing, if available, would increase our fixed payment obligations and may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, acquiring, selling or licensing intellectual property rights, and making capital expenditures, declaring dividends, repurchase shares of our common stock, or other operating restrictions that could adversely impact our ability to conduct our business. We could also be required to meet certain milestones in connection with debt financing and the failure to achieve such milestones by certain dates may force us to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us which could have a material adverse effect on our business, operating results and prospects.

Current wording

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through one or a combination of private and public equity offerings (such as the private placement of our common stock in August 2023 and sales of common stock under an "at-the-market" stock offering program in January 2024), debt financings, collaborations, strategic alliances and licensing arrangements. We do not have any committed external source of funds. The terms of any financing may adversely affect the holdings or the rights of our stockholders and the issuance of additional securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our shares to decline. To the extent that we raise additional capital through the sale of common stock or securities convertible or exchangeable into common stock, the ownership interest of our existing common stockholders will be diluted, and the terms of those securities may include liquidation or other preferences that may materially adversely affect your rights as a common stockholder. Debt financing, if available, would increase our fixed payment obligations and may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, acquiring, selling or licensing intellectual property rights, and making capital expenditures, declaring dividends, repurchase shares of our common stock, or other operating restrictions that could adversely impact our ability to conduct our business. We could also be required to meet certain milestones in connection with debt financing and the failure to achieve such milestones by certain dates may force us to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us which could have a material adverse effect on our business, operating results and prospects.

Previous wording

We have not yet demonstrated our ability to complete clinical trials, including large-scale, pivotal clinical trials, obtain regulatory approvals, manufacture a commercial scale product or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful commercialization. We received FDA clearance of four IND applications for each of TNG908, TNG462, TNG260 and TNG348. We may not be able to file any future INDs for any of our other product candidates on the timelines we expect, if at all. Further, timelines for developing and filing INDs are subject to significant uncertainties and projected timelines can be delayed. Moreover, we cannot be sure that submission of an IND will result in the FDA allowing clinical trials to begin, or that, once begun, issues will not arise that require us to suspend or terminate clinical trials. Any guidance we receive from the FDA or other regulatory authorities is subject to change. These regulatory authorities could change their position, including on the acceptability of our trial designs or the clinical endpoints selected, which may require us to complete additional clinical trials or result in the imposition of stricter approval conditions than we currently expect. Successful completion of our clinical trials is a prerequisite to submitting an NDA to the FDA, a Marketing Authorization Application, or MAA, to the European Medicines Agency, or EMA, or other marketing applications to regulatory authorities in other jurisdictions, for each product candidate and, consequently, the regulatory approval of each product candidate. While the INDs for TNG908, TNG462, TNG260 and TNG348 were cleared by the FDA, it is possible that an adequate number of patients may not be enrolled on a timely basis, or at all, and these studies may not be completed (and preliminary, initial or final trial results may not be available) on time, or at all. Similarly, future clinical trials may not begin on time or be completed on schedule, if at all.

Current wording

We have not yet demonstrated our ability to complete clinical trials, including large-scale, pivotal clinical trials, obtain regulatory approvals, manufacture a commercial scale product or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful commercialization. Although we have received FDA clearance of five IND applications (TNG908, TNG462, TNG260, TNG348, and TNG456), we have since discontinued development of TNG348 and TNG908. We may not be able to file any future INDs for any of our other product candidates on the timelines we expect, if at all. Further, timelines for developing and filing INDs are subject to significant uncertainties and projected timelines can be delayed. Moreover, we cannot be sure that submission of an IND will result in the FDA allowing clinical trials to begin, or that, once begun, issues will not arise that require us to suspend or terminate clinical trials. Any guidance we receive from the FDA or other regulatory authorities is subject to change. These regulatory authorities could change their position, including on the acceptability of our trial designs or the clinical endpoints selected, which may require us to complete additional clinical trials or result in the imposition of stricter approval conditions than we currently expect. Successful completion of our clinical trials is a prerequisite to submitting an NDA to the FDA, a Marketing Authorization Application, or MAA, to the European Medicines Agency, or EMA, or other marketing applications to regulatory authorities in other jurisdictions, for each product candidate and, consequently, the regulatory approval of each product candidate. While the INDs for TNG908, TNG462, TNG260, TNG348, and TNG456 were cleared by the FDA, such clearance does not ensure that an adequate number of patients will be enrolled on a timely basis, or at all or that the clinical trials will be completed on time, or at all. For example, in May 2024, we announced that we were discontinuing development of our TNG348 program due to liver toxicity observed in the dose escalation portion of our Phase 1/2 clinical trial, and in November 2024, we announced that we were discontinuing development of TNG908 to fully resource TNG462 and TNG456 development.

Previous wording

Our preclinical studies, our four ongoing clinical trials and future clinical trials may not be successful. It is impossible to predict when or if any of our product candidates will prove effective and safe in humans or will receive regulatory approval. Before obtaining regulatory approval from regulatory authorities for the sale of any product candidate, we must complete preclinical studies and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and outcomes are uncertain. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical development testing and early clinical trials may not be predictive of the success of later clinical trials, and interim or preliminary results of a clinical trial do not necessarily predict final results (or be indicative of safety and efficacy if commercialized and used in a broader population). Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain regulatory approval of their product candidates.

Current wording

Our preclinical studies, our ongoing clinical trials and future clinical trials may not be successful. It is impossible to predict when or if any of our product candidates will prove effective and safe in humans or will receive regulatory approval. Before obtaining regulatory approval from regulatory authorities for the sale of any product candidate, we must complete preclinical studies and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and outcomes are uncertain. A failure of one or more clinical trials can occur at any stage of testing. For example, in May 2024, we announced that we were discontinuing development of our TNG348 program due to liver toxicity observed in the dose escalation portion of our Phase 1/2 clinical trial. The outcome of preclinical development testing and early clinical trials may not be predictive of the success of later clinical trials, and interim or preliminary results of a clinical trial do not necessarily predict final results (or be indicative of safety and efficacy if commercialized and used in a broader population). Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain regulatory approval of their product candidates.

Previous wording

If we or third parties are unable to successfully develop screening technology for biomarkers that enable patient selection, or experience significant delays in doing so, we may be unable to commercialize our product candidates or we may not realize the full commercial potential of our product candidates.

Current wording

If we or third parties are unable to successfully develop screening technology for biomarkers that enable patient selection and/or target engagement, or experience significant delays in doing so, we may be unable to commercialize our product candidates or we may not realize the full commercial potential of our product candidates.

Previous wording

A key component of our strategy includes the use of next-generation sequencing to guide patient selection and/or to confirm target engagement of our product candidates. We rely on third-parties to provide this technology. It is not always the case, however, that the biomarker we have identified for patient selection is on the panel offered by certain next generation technology sequencing providers. If not already commercially available, we may collaborate with next-generation sequencing companies for the development of biomarkers associated with our product candidates. We may have difficulty in establishing or maintaining such development relationships, and we will face competition from other companies in establishing these collaborations.

Current wording

A key component of our strategy includes the use of biomarker testing to guide patient selection for our product candidates and/or target engagement for our product candidates. We rely on third-parties to provide this technology. It is not always the case, however, that the biomarker we have identified for patient selection and/or target engagement is included in a commercially available test offered by biomarker testing providers. If not already commercially available, we may collaborate with biomarker assay development companies for the development of biomarkers associated with our product candidates. We may have difficulty in establishing or maintaining such development relationships, and we will face competition from other companies in establishing these collaborations.

Previous wording

There are also several risks associated with biomarker identification and validation. We, in collaboration with any diagnostic partners, may not be able to identify predictive biomarkers or pharmacodynamic biomarkers for one or more of our programs. We may not be able to validate potential biomarkers (e.g., certain genetic mutations) or their functional relevance in relevant in vitro or in vivo models. Data analytics and information from databases that we rely on for identifying or validating some of our biomarker-target relationships may not accurately reflect potential patient populations. Potential biomarkers, even if validated preclinically, may not be functionally effective or validated in human clinical trials.

Current wording

There are also several risks associated with biomarker identification and validation. We, in collaboration with any diagnostic partners, may not be able to identify predictive pharmacodynamic biomarkers for one or more of our programs. We may not be able to validate potential biomarkers (e.g., certain genetic mutations) or their functional relevance in relevant in vitro or in vivo models. Data analytics and information from databases that we rely on for identifying or validating some of our biomarker-target relationships may not accurately reflect potential patient populations. Potential biomarkers, even if validated preclinically, may not be functionally effective or validated in human clinical trials.

Previous wording

If next generation sequencing companies experience any delays including the biomarkers we have identified for patient selection on their panels or tests, or if they do not include those biomarkers on their panels or tests, our clinical trials may be delayed or may not identify sufficient patients to complete the trial and our clinical trials may be unsuccessful and our therapies will not advance to approval.

Current wording

If biomarker assay development companies experience any delays developing and launching the biomarkers we have identified for patient selection and/or target engagement, our clinical trials may be delayed or may not identify sufficient patients to complete the trial and our clinical trials may be unsuccessful and our therapies will not advance to approval.

Previous wording

We intend to rely on third parties for the design, development and manufacture of companion diagnostic tests for our therapeutic product candidates that may require such tests. If we enter into such collaborative agreements, we will be dependent on the sustained cooperation and effort of our future collaborators in developing and obtaining approval for these companion diagnostics. It may be necessary to resolve issues such as selectivity/specificity, analytical validation, reproducibility, or clinical validation of companion diagnostics during the development and regulatory approval processes. Moreover, even if data from preclinical studies and early clinical trials appear to support development of a companion diagnostic for a product candidate, data generated in later clinical trials may fail to support the analytical and clinical validation of the companion diagnostic. We and our future collaborators may encounter difficulties in developing, obtaining regulatory clearance or approval for, manufacturing and commercializing companion diagnostics similar to those we face with respect to our therapeutic product candidates themselves, including issues with achieving regulatory clearance or approval, production of sufficient quantities at commercial scale and with appropriate quality standards, and in gaining market acceptance. If we (or any third party we may engage) are unable to successfully develop companion diagnostics for these therapeutic product candidates, or experience delays in doing so, the development and commercialization of these therapeutic product candidates may be adversely affected, these therapeutic product candidates may not obtain regulatory approval, and we may not realize the full commercial potential of any of these therapeutic products that obtain regulatory approval.

Current wording

We intend to rely on third parties for the design, development and manufacture of companion diagnostic tests for our therapeutic product candidates that may require such tests. If we enter into such collaborative agreements, we will be dependent on the sustained cooperation and effort of our future collaborators in developing and obtaining approval for these companion diagnostics. We must characterize the selectivity, specificity, sensitivity, reproducibility, analytical validation, and clinical validation of companion diagnostics during the development and regulatory approval processes. Moreover, even if data from preclinical studies and early clinical trials appear to support development of a companion diagnostic for a product candidate, data generated in later clinical trials may fail to support the analytical and clinical validation of the companion diagnostic. We and our future collaborators may encounter difficulties in developing, obtaining regulatory clearance or approval for, manufacturing and commercializing companion diagnostics similar to those we face with respect to our therapeutic product candidates themselves, including issues with achieving regulatory clearance or approval, production of sufficient quantities at commercial scale and with appropriate quality standards, and in gaining market acceptance. If we (or any third party we may engage) are unable to successfully develop companion diagnostics for these therapeutic product candidates, or experience delays in doing so, the development and commercialization of these therapeutic product candidates may be adversely affected, these therapeutic product candidates may not obtain regulatory approval, and we may not realize the full commercial potential of any of these therapeutic products that obtain regulatory approval.

Previous wording

We may from time to time indicate the intent to publicly disclose certain clinical trial data at a future date. We have, for example, noted that we will provide an update on the TNG908 clinical trial in 2024. Due to the factors described above, and elsewhere in these Risk Factors, we may be unable to report data on or before the time indicated to investors, we may not have the data to provide the information indicative of safety or efficacy, and even if we do provide such clinical trial data, the final results from that phase of the clinical trial may be different from what we disclose initially.

Current wording

We may from time to time indicate the intent to publicly disclose certain clinical trial data at a future date. We have, for example, noted that we will provide a clinical update on the TNG462 clinical trial and clinical data on the TNG260 clinical trial in 2025. Due to the factors described above, and elsewhere in these Risk Factors, we may be unable to report data on or before the time indicated to investors, we may not have the data to provide the information indicative of safety or efficacy, the data may not be sufficiently mature or the number of patients with a specific histology may be inadequate to draw conclusions about the effectiveness of the therapy, and even if we do provide such clinical trial data, the final results from that phase of the clinical trial may be different from what we disclose initially.

Previous wording

we may experience delays in reaching, or fail to reach, agreement on acceptable terms with prospective trial sites and prospective CROs, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;

Current wording

we may experience delays in reaching, or fail to reach, agreement on acceptable terms with prospective trial sites and prospective CROs to conduct our trials, the terms of which can be subject to extensive negotiation and may vary significantly among different trial sites and CROs;

Previous wording

the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trials or fail to return for post-treatment follow-up at a higher rate than we anticipate;

Current wording

the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or we may fail to enroll patients with certain cancer indications, such as pancreatic and lung cancer, that we are focusing on in connection with TNG462 (and GBM, which is our focus for TNG456), or participants may drop out of these clinical trials or fail to return for post-treatment follow-up at a higher rate than we anticipate;

Previous wording

we may elect to, or regulators or IRBs or ethics committees may require us or our investigators to, suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants in our clinical trials are being exposed to unacceptable health risks;

Current wording

we may elect to, or regulators, IRBs or ethics committees may require us or our investigators to, suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants in our clinical trials are being exposed to unacceptable health risks;

Previous wording

We may not be able to initiate, continue or complete clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or comparable foreign regulatory authorities, or as needed to provide appropriate statistical power for a given trial. In particular, because we are focused on patients with specific genetic mutations for the development of our precision oncology programs and because some of the indications we are pursuing are orphan indications that have small populations, our ability to enroll eligible patients may be limited or may result in slower enrollment than we anticipate. We also may experience slower enrollment as a result of limited trial populations due to competitor trials or other factors beyond our control. Delays in enrollment may affect the timing of any results from our trials (as well as the timing for dose escalation and dose expansion) and therefore the regulatory approval (if any) for any of our product candidates may extend beyond the period we have targeted or beyond the timeline expected by investors.

Current wording

We may not be able to initiate, continue or complete clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or comparable foreign regulatory authorities, or as needed to provide appropriate statistical power for a given trial. In particular, because we are focused on patients with specific genetic mutations for the development of our precision oncology programs and because some of the indications we are pursuing, including pancreatic cancer in connection with TNG462 and GBM in connection with TNG456, are orphan indications that have small populations, our ability to enroll eligible patients may be limited or may result in slower enrollment than we anticipate. We also may experience slower enrollment as a result of limited trial populations due to clinical trials run by us or our competitors or other factors beyond our control. Delays in enrollment may affect the timing of any results or data announcements from our trials (as well as the timing for dose escalation and dose expansion) and therefore the regulatory approval (if any) for any of our product candidates may extend beyond the period we have targeted or beyond the timeline expected by investors.

Previous wording

The patient eligibility criteria defined in our trial protocols, including biomarker-driven identification, may limit the patient populations eligible for our clinical trials to a greater extent than competing clinical trials for the same indication that do not have biomarker-driven patient eligibility criteria. We also rely on the willingness and ability of clinicians to screen their patients for biomarkers to indicate which patients may be eligible for enrollment in our clinical trials.

Current wording

The patient eligibility criteria defined in our trial protocols, including biomarker-driven identification or the number of prior treatment lines, may limit the patient populations eligible for our clinical trials to a greater extent than competing clinical trials for the same indication that do not have biomarker-driven patient eligibility criteria. We also rely on the willingness and ability of clinicians to screen their patients for biomarkers to indicate which patients may be eligible for enrollment in our clinical trials.

Previous wording

In addition, some of our competitors have ongoing clinical trials for product candidates that treat the same indications as do our product candidates, and patients who would otherwise be eligible for our clinical trials may choose instead to enroll in clinical trials of our competitors’ product candidates (for example, three INDs for other companies have been cleared by the FDA for clinical trials of MTA-cooperative PRMT5 inhibitors for the treatment of cancer patients, and such trials have already enrolled patients and those trials are using some of the same clinical trial sites that we use). Further, the target patient population eligible for the TNG462 clinical trial is largely the same as for the TNG908 clinical trial. As a result, our own trials may compete to enroll patients among a limited population and thus each of our own trials may experience delays or limited enrollment.

Current wording

In addition, some of our competitors have ongoing clinical trials for product candidates that aim to treat the same indications as our product candidates, and patients who would otherwise be eligible for our clinical trials may choose instead to enroll in clinical trials of our competitors’ product candidates (for example, multiple INDs for other companies have been cleared by the FDA for clinical trials of MTA-cooperative PRMT5 inhibitors for the treatment of cancer patients, and such trials have already enrolled patients and those trials are using some of the same clinical trial sites that we use). Further, the target patient population eligible for the TNG462 and TNG456 clinical trials overlap. In particular, each of these clinical trials has arms that are expected to aim to enroll patients with lung cancer. As a result, our own trials may compete to enroll patients among a limited population and thus each of our own trials may experience delays or limited enrollment or we may be compelled to explore enrollment in new countries to gain access to an expanded patient population.

Previous wording

In addition to the competitive trial environment, the eligibility criteria of our clinical trials will further limit the pool of available study participants as we will require that patients have specific characteristics that we can measure to assure their cancer is either severe enough or not too advanced to include them in a study. The process of finding patients may prove costly. We also may not be able to identify, recruit or enroll a sufficient number of patients to complete our clinical studies because of the perceived risks and benefits of the product candidates under study, the availability and efficacy of competing therapies and clinical trials, the proximity and availability of clinical trial sites for prospective patients, and the patient referral practices of physicians. If patients are unwilling to participate in our studies for any reason, the timeline for recruiting patients, conducting studies, reporting initial and final trial results and obtaining regulatory approval of potential products may be delayed.

Current wording

In addition to the competitive clinical trial environment, the eligibility criteria of our clinical trials will further limit the pool of available study participants as we will require that patients have specific characteristics that we can measure to assure their cancer is either severe enough or not too advanced to include them in a study. The process of finding patients may prove costly. We also may not be able to identify, recruit or enroll a sufficient number of patients (or sufficient patients who have limited lines of prior therapy) to complete our clinical studies because of the perceived risks and benefits of the product candidates under study, the availability and efficacy of competing therapies and clinical trials, the proximity and availability of clinical trial sites for prospective patients, and the patient referral practices of physicians. If patients are unavailable or unwilling to participate in our studies for any reason, the timeline for recruiting patients, conducting studies, reporting initial and final trial results and obtaining regulatory approval of potential products may be delayed.

Previous wording

Further, if we are unable to identify patients with the targeted genetic mutations for our clinical trials, this could compromise our ability to seek designations under applicable FDA expedited review and development programs, including Breakthrough Therapy Designation and Fast Track Designation (to the extent these are available to us), or otherwise seek to accelerate clinical development and regulatory timelines. Patient enrollment may be affected by other factors, including:

Current wording

Further, if we are unable to identify patients with the targeted genetic mutations for our clinical trials, it could compromise our ability to seek designations under applicable FDA expedited review and development programs, including Breakthrough Therapy Designation and Fast Track Designation (to the extent these are available to us), or otherwise seek to accelerate clinical development and regulatory timelines. Patient enrollment may be affected by other factors, including:

Previous wording

factors we may not be able to control, including the impacts of any epidemics or pandemics, that may limit patients, principal investigators or staff or clinical site availability.

Current wording

factors we may not be able to control, including the impacts of any epidemics or pandemics, which may limit patients, principal investigators or staff or clinical site availability.

Previous wording

We anticipate that certain of our current product candidates and future product candidates could be used in combination with third-party drugs or biologics, some of which are still in development, and we have limited or no control over the supply, regulatory status, or regulatory approval of such other drugs or biologics.

Current wording

We anticipate that certain of our current and future product candidates could be used in combination with third-party drugs or biologics, some of which are still in development, and we have limited or no control over the supply, regulatory status, or regulatory approval of such other drugs or biologics.

Previous wording

Certain of our current product candidates and any future product candidates may have the potential to be administered in combination with existing standards of care such as checkpoint inhibitor immunotherapies, chemotherapies, targeted therapies or radiotherapy. Our ability to develop and ultimately commercialize our current programs and product candidates and any future programs or product candidates for use in combination with other therapies will depend on our ability to access such drugs or biologics on commercially reasonable terms for the clinical trials and their availability for use with our commercialized product, if approved. We cannot be certain that current or potential future commercial relationships will provide us with a steady supply of such drugs or biologics on commercially reasonable terms, or at all.

Current wording

Certain of our current product candidates and any future product candidates may have the potential to be administered in combination with existing standards of care (such as checkpoint inhibitor immunotherapies, chemotherapies, targeted therapies or radiotherapy) or with other classes of therapeutics agents (such as the RAS(ON) multi- and G12D- inhibitors from RevMed with which we plan to evaluate TNG462 in combination clinical trials and abemaciclib, with which we plan to evaluate TNG456 in a combination clinical trial). Our ability to develop and ultimately commercialize our current programs and product candidates and any future programs or product candidates for use in combination with other therapies will depend on our ability to access such drugs or biologics on commercially reasonable terms for the clinical trials and their availability for use with our commercialized product, if approved. We have entered into separate clinical collaboration and supply agreements with RevMed and Lilly, under which we plan to conduct combination clinical trials with RevMed's RAS(ON) multi- and G12D-selective inhibitors and Lilly's abemaciclib, respectively. Additionally, we plan to purchase pembrolizumab for use in combination with TNG462. Nevertheless, we cannot be certain that current or potential future commercial relationships will continue to provide us with a steady supply of such drugs or biologics on commercially reasonable terms, or at all.

Previous wording

Any failure to maintain or enter into new successful commercial relationships, or the expense of purchasing checkpoint inhibitor immunotherapies or other potential combination or comparator therapies in the market, may delay our development timelines, increase our costs and jeopardize our ability to develop our current product candidates and any future product candidates as commercially viable therapies. If any of these circumstances occur, our business, financial condition, operating results, stock price and prospects may be materially harmed.

Current wording

Any failure to maintain or enter into new commercial relationships, or the expense of purchasing checkpoint inhibitor immunotherapies or other potential combination or comparator therapies in the market, may delay our development timelines, increase our costs and jeopardize our ability to develop our current product candidates and any future product candidates as commercially viable therapies. If any of these circumstances occur, our business, financial condition, operating results, stock price and prospects may be materially harmed.

Previous wording

We have two clinical trials that are testing the safety and efficacy of combination therapies: (i) TNG260 is being tested in combination with an anti-PD-1 antibody, pembrolizumab; and (ii) TNG348 is being tested as a single agent and in combination with a PARP inhibitor, olaparib. The clinical development of combination therapies may be more complex than the development of single agent therapies and generally requires that we are able to describe and demonstrate the contribution of each product to the safety and efficacy of the combination as a whole. This requirement may make the design and conduct of clinical trials more complex (which may cause delays in the trial or require additional data to be collected and analyzed, which, in turn, may limit any patent protection or regulatory exclusivity periods we have to market the product candidate). In addition, we expect this would increase the anticipated costs that we incur in connection with the seeking regulatory approval of the combination. Further, the FDA's "combination rule" prohibits the FDA approving a fixed-dose combination product unless each component of a proposed drug product contributes to the claimed effects and the dosage of each component (amount, frequency, duration) is safe and effective for the intended population. This typically requires a clinical factorial study, designed to assess the effects attributable to each drug in the combination product, particularly when the ingredients are directed at the same sign or symptom of the disease or condition. Moreover, the applicable requirements for approval of a combination therapy may differ from country to country.

Current wording

We have one clinical trial currently testing the safety and efficacy of a combination therapy (TNG260 is being tested in combination with an anti-PD-1 antibody, pembrolizumab), and have additional clinical trials planned to evaluate (i) TNG462 in multiple different combinations, including with each of RevMed's RAS(ON) multi- and G12D- selective inhibitors and with pembrolizumab and (ii) TNG456 with abemaciclib. The clinical development of combination therapies may be more complex than the development of single agent therapies and generally requires that we are able to describe and demonstrate the contribution of each product to the safety and efficacy of the combination as a whole. This requirement may make the design and conduct of clinical trials more complex (which may cause delays in the trial or require additional data to be collected and analyzed, which, in turn, may limit any patent protection or regulatory exclusivity periods we have to market the product candidate). In addition, we expect this would increase the anticipated costs that we incur in connection with the seeking regulatory approval of the combination. Further, the FDA's "combination rule" prohibits the FDA approving a fixed-dose combination product unless each component of a proposed drug product contributes to the claimed effects and the dosage of each component (amount, frequency, duration) is safe and effective for the intended population. This typically requires a clinical factorial study, designed to assess the effects attributable to each drug in the combination product, particularly when the ingredients are directed at the same sign or symptom of the disease or condition. Moreover, the applicable requirements for approval of a combination therapy may differ from country to country.

Previous wording

Moreover, following product approval of a combination therapy, the FDA or comparable foreign regulatory authorities may require that products used in conjunction with each other be cross labeled for combined use. To the extent that we do not have rights to the other product, this may require us to work with a third party to satisfy such a requirement. Moreover, developments related to the other product may impact our clinical trials for the combination as well as our commercial prospects should we receive regulatory approval. Such developments may include changes to the other product’s safety or efficacy profile, changes to the availability of the other product, quality, manufacturing and supply issues with respect to the other product, and changes to the standard of care.

Current wording

Moreover, following product approval of a combination therapy, the FDA or comparable foreign regulatory authorities may require that products used in conjunction with each other be cross labeled for combined use. To the extent that we do not have rights to the other product, this may require us to work with a third party to satisfy such a requirement (which we ay be unable to do on reasonable terms, or at all). Moreover, developments related to the other product may impact our clinical trials for the combination as well as our commercial prospects should we receive regulatory approval. Such developments may include changes to the other product’s safety or efficacy profile, changes to the availability of the other product, quality, manufacturing and supply issues with respect to the other product, and changes to the standard of care.

Previous wording

Before obtaining regulatory approvals for the commercial sale of any products, we must demonstrate through lengthy, complex and expensive preclinical studies and clinical trials that our product candidates are both safe and effective for use in each target indication. Clinical testing is expensive and can take many years to complete, and outcomes are inherently uncertain. Failure can occur at any time during the clinical trial process. Because our precision oncology programs and our product candidates are in early stages of development, there is a high risk of failure, and we may never succeed in developing marketable products. There is typically an extremely high rate of attrition from the failure of product candidates proceeding through clinical trials. Product candidates in later stages of clinical trials also may fail to show the desired safety and efficacy profile despite having progressed through nonclinical studies and initial clinical trials. If the results of our current and future preclinical studies and clinical trials are inconclusive with respect to the safety, pharmacokinetics or efficacy of our product candidates, if we do not meet the clinical endpoints with statistical and clinically meaningful significance, or if there are safety concerns associated with our product candidates, we may be prevented from, or delayed in, obtaining regulatory approval for such product candidates. In some instances, there can be significant variability in safety or efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants. There may be side effects experienced during clinical trials in connection with the use of oncology therapies. Results of our trials could reveal a high and unacceptable severity and prevalence of side effects as a result of the use of our therapy (or due to other factors). In such an event, our trials could be suspended or terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our product candidates for any or all targeted indications. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Product liability claims can be expensive to defend and result in significant damages and harm to our reputation. While we do have insurance to cover certain product liability claims, including in connection with certain injury during clinical trials, the coverage may not may not cover all injuries, be sufficient to cover all expenses related to any injury and we may be required to pay damages from our own resources and the amount of such damages may be significant.

Current wording

Before obtaining regulatory approvals for the commercial sale of any products, we must demonstrate through lengthy, complex and expensive preclinical studies and clinical trials that our product candidates are both safe and effective for use in each target indication. Clinical trials are expensive and can take many years to complete, and outcomes are inherently uncertain. Failure can occur at any time during the clinical trial process. Because our precision oncology programs and our product candidates are in early stages of development, there is a high risk of failure, and we may never succeed in developing marketable products. There is typically an extremely high rate of attrition from the failure of product candidates proceeding through clinical trials. Product candidates in later stages of clinical trials also may fail to show the desired safety and efficacy profile despite having progressed through nonclinical studies and initial clinical trials. If the results of our current and future preclinical studies and clinical trials are inconclusive with respect to the safety, pharmacokinetics or efficacy of our product candidates, if we do not meet the clinical endpoints with statistical and clinically meaningful significance, or if there are safety concerns associated with our product candidates, we may be prevented from, or delayed in, obtaining regulatory approval for such product candidates. In some instances, there can be significant variability in safety or efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants. There may be side effects experienced during clinical trials in connection with the use of oncology therapies. Results of our trials could reveal a high and unacceptable severity and prevalence of side effects as a result of the use of our therapy (or due to other factors). In such an event, we could decide to suspend or terminate a trial or program, or the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our product candidates for any or all targeted indications. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Product liability claims can be expensive to defend and result in significant damages and harm to our reputation. While we do have insurance to cover certain product liability claims, including in connection with certain injury during clinical trials, the coverage may not cover all injuries, be sufficient to cover all expenses related to any injury and we may be required to pay damages from our own resources and the amount of such damages may be signifi…

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