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 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.

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, vopimetostat, 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, 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.

Current wording

We have incurred significant net losses since our inception. As of December 31, 2025, we had an accumulated deficit of $603.2 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

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);

Current wording

timely complete patient enrollment and patient dosing in our current and future clinical trials (including our current trials of vopimetostat (as a monotherapy and in combination), TNG456 (as a monotherapy and in combination), and TNG260;

Previous wording

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

Current wording

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

Previous wording

 successfully enroll the patients with specific cancers that are the focus of our clinical trials, such as patients with limited prior treatment lines in pancreatic and lung cancer for our ongoing monotherapy trial for TNG462;

Current wording

successfully enroll the patients with specific cancers and prior treatment that are the focus of our clinical trials, such as patients with limited prior treatment lines in pancreatic and lung cancer for our ongoing monotherapy and combination trials for vopimetostat;

Previous 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.

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 enrolling patients in multiple 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 (including multiple combination clinical trials and our pivotal trial), 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 have successfully raised capital in the past, including most recently by raising $225.0 million in aggregate gross proceeds from the underwritten offering and concurrent private placement of common shares and pre-funded warrants to purchase common shares in October 2025 and proceeds of $62.1 million from our "at the market" stock offering program during the first quarter of 2026, and through March 2, 2026, 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, 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:

Current wording

We believe that our existing cash, cash equivalents and marketable securities on hand as of December 31, 2025 will enable us to fund our operating expenses and capital expenditure requirements at least into 2028. However, our future capital requirements will depend on and could increase significantly as a result of many factors, including:

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);

Current wording

the cost of acquiring or supplying therapies to be used in combination clinical trials;

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 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.

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 underwritten offering and concurrent private placement of common shares and pre-funded warrants in October 2025 and sales of common stock under an "at-the-market" stock offering program in in the first quarter of 2026), 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. 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.

Current wording

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, vopimetostat, 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 vopimetostat and TNG456 development.

Previous wording

The discovery and development of oncology therapeutics for patients with genetically defined or biomarker-driven cancers is a rapidly evolving area, and the scientific discoveries that form the basis for our efforts to discover and develop product candidates are relatively new. Our proprietary functional genomics discovery approach is based on the genetic concept of synthetic lethality. The scientific evidence to support the feasibility of developing product candidates based on these discoveries is both preliminary and limited. Although we believe, based on our preclinical work, that the genetic markers targeted by our programs drive the formation and spread of certain cancers, clinical results may not confirm this hypothesis or may only confirm it for certain alterations or certain tumor types. The patient populations for our product candidates are limited to those with specific target alterations and may not be completely defined but are substantially smaller than the general treated cancer population, and we will need to screen and identify these patients with targeted alterations. Successful identification of patients is dependent on several factors, including achieving certainty as to how specific alterations respond to our product candidates and the ability to identify such alterations. Furthermore, even if we are successful in identifying patients with specific targets, we cannot be certain that the resulting patient populations with each mutation will be as large as we anticipate, large enough to allow us to successfully obtain approval for each such mutation and commercialize our product candidates and achieve profitability.

Current wording

The discovery and development of oncology therapeutics for patients with genetically defined or biomarker-driven cancers is a rapidly evolving area, and the scientific discoveries that form the basis for our efforts to discover and develop product candidates are relatively new. Our proprietary functional genomics discovery approach is based on the genetic concept of synthetic lethality. The scientific evidence to support the feasibility of developing product candidates based on these discoveries is both preliminary and limited. Although we believe, based on our preclinical work, that the genetic markers targeted by our programs drive the formation and spread of certain cancers, clinical results may not confirm this hypothesis or may only confirm it for certain alterations or certain tumor types. The patient populations for our product candidates (and our combination clinical trials) are limited to those with specific target alterations and may not be completely defined but are substantially smaller than the general treated cancer population, and we will need to screen and identify these patients with targeted alterations. Successful identification of patients is dependent on several factors, including achieving certainty as to how specific alterations respond to our product candidates and the ability to identify such alterations. Furthermore, even if we are successful in identifying patients with specific targets, we cannot be certain that the resulting patient populations with each mutation will be as large as we anticipate, large enough to allow us to successfully obtain approval for each such mutation and commercialize our product candidates and achieve profitability.

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 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.

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 in 2026 we will provide a clinical update on the lung cohort of the vopimetostat monotherapy clinical trial and initial data from the Phase 1/2 combination clinical trial with RAS(ON) inhibitors from RevMed. 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

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;

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 vopimetostat (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

our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or IRBs or ethics committees to suspend or terminate the trials, or reports may arise from preclinical or clinical testing of other cancer therapies that raise safety or efficacy concerns about our product candidates;

Current wording

our product candidates (or our product candidates in combination with other products or product candidates) may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or IRBs or ethics committees to suspend or terminate the trials, or reports may arise from preclinical or clinical testing of other cancer therapies that raise safety or efficacy concerns about our product candidates;

Previous wording

regulatory developments with respect to our competitors’ products, including any developments, litigation or public concern about the safety of such products.

Current wording

regulatory developments may occur with respect to our competitors’ products, including any developments, litigation or public concern about the safety of such products.

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, 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.

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, including our planned pivotal trial, 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 vopimetostat 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

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.

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 vopimetostat 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 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.

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, including our planned pivotal trial, 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

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.

Current wording

Certain of our current and future product candidates are being used in combination or we anticipate 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) 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.

Current wording

Certain of our current product candidates are being administered or 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 are evaluating vopimetostat 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, Lilly, and Erasca, under which we plan to conduct combination clinical trials with RevMed's RAS(ON) multi- and G12D-selective inhibitors, Lilly's abemaciclib and Erasca’s pan-RAS molecular glue, respectively. Additionally, we have purchased pembrolizumab for use in combination with vopimetostat. 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 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 commercial prospects may be materially harmed.

Previous 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.

Current wording

We have several ongoing and planned clinical trials testing the safety and efficacy of combination therapies, including: evaluating (i) vopimetostat 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. We plan to evaluate vopimetostat with Erasca’s pan-RAS molecular glue. 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 seeking regulatory approval of the combination or in commercializing a combination therapy. 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 (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.

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 may 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

Certain of our product candidates will be used, and future product candidates may be used, in combination with one or more cancer therapies. The uncertainty resulting from the use of our product candidates in combination with other cancer therapies may make it difficult to accurately predict side effects in future clinical trials or the combination product may cause negative effects resulting from drug-drug interactions in clinical trials. As is the case with many treatments for cancer and rare diseases, it is likely that there may be side effects associated with the use of our product candidates. If significant adverse events or other side effects are observed in the clinical trials of our product candidates or when used in combination with another therapy, we may have difficulty recruiting patients to our clinical trials, patients may drop out of our clinical trials, or we may be required to abandon the trials or our development efforts of one or more product candidates altogether. We, the FDA or other applicable regulatory authorities, or an IRB, may suspend or terminate clinical trials of a product candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to unacceptable health risks or adverse side effects. 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. Even if the side effects do not preclude the monotherapy or the combination products from obtaining or maintaining regulatory approval, undesirable side effects may inhibit market acceptance of the approved combination products due to their tolerability versus other therapies. Any of these developments could materially harm our business, operating results, financial condition and prospects.

Current wording

Certain of our product candidates are being tested, and future product candidates may be used, in combination with one or more cancer therapies. The uncertainty resulting from the use of our product candidates in combination with other cancer therapies may make it difficult to accurately predict side effects in future clinical trials or the combination product may cause negative effects resulting from drug-drug interactions in clinical trials. As is the case with many treatments for cancer and rare diseases, it is likely that there may be side effects associated with the use of our product candidates. If significant adverse events or other side effects are observed in the clinical trials of our product candidates or when used in combination with another therapy, we may have difficulty recruiting patients to our clinical trials, patients may drop out of our clinical trials, or we may be required to abandon the trials or our development efforts of one or more product candidates altogether. We, the FDA or other applicable regulatory authorities, or an IRB, may suspend or terminate clinical trials of a product candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to unacceptable health risks or adverse side effects. 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. Even if the side effects do not preclude the monotherapy or the combination products from obtaining or maintaining regulatory approval, undesirable side effects may inhibit market acceptance of the approved combination products due to their tolerability versus other therapies. Any of these developments could materially harm our business, operating results, financial condition and prospects.

Previous wording

We currently conduct certain clinical trials outside the United States, and expect we will continue to do so in the future, and these jurisdictions may include countries in Europe, Asia, Australia or other foreign jurisdictions. For example, we are conducting clinical trials for TNG462 in France and Spain. The acceptance of trial data from clinical trials conducted outside the United States by the FDA, or comparable foreign regulatory authorities, may be subject to certain conditions. In cases where data from clinical trials conducted outside the United States are intended to serve as the sole basis for regulatory approval in the United States, the FDA will generally not approve the application on the basis of foreign data alone unless: (i) the data are applicable to the United States population and United States medical practices, (ii) the trials were performed by clinical investigators of recognized competence and pursuant to Good Clinical Practices, or GCP, regulations; and (iii) the data may be considered valid without the need for an on-site inspection by the FDA, or if the FDA considers such inspection to be necessary, the FDA is able to validate the data through on-site inspection or other appropriate means. Additionally, the FDA’s clinical trial requirements, including sufficient size of patient populations and statistical powering, must be met. Many foreign regulatory authorities have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the United States or the applicable jurisdiction. If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of our business plan, and which may result in our product candidates approval being significantly delayed, or not receiving regulatory approval or clearance for commercialization in the applicable jurisdiction.

Current wording

We currently conduct certain clinical trials outside the United States, and expect we will continue to do so in the future, and these jurisdictions may include countries in Europe, Asia, Australia or other foreign jurisdictions. For example, we are conducting clinical trials for vopimetostat in France and Spain and anticipate expanding to additional geographies for our upcoming pivotal trial. The acceptance of trial data from clinical trials conducted outside the United States by the FDA, or comparable foreign regulatory authorities, may be subject to certain conditions. In cases where data from clinical trials conducted outside the United States are intended to serve as the sole basis for regulatory approval in the United States, the FDA will generally not approve the application on the basis of foreign data alone unless: (i) the data are applicable to the United States population and United States medical practices, (ii) the trials were performed by clinical investigators of recognized competence and pursuant to Good Clinical Practices, or GCP, regulations; and (iii) the data may be considered valid without the need for an on-site inspection by the FDA, or if the FDA considers such inspection to be necessary, the FDA is able to validate the data through on-site inspection or other appropriate means. Additionally, the FDA’s clinical trial requirements, including sufficient size of patient populations and statistical powering, must be met. Many foreign regulatory authorities have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the United States or the applicable jurisdiction. If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of our business plan, and which may result in our product candidates approval being significantly delayed, or not receiving regulatory approval or clearance for commercialization in the applicable jurisdiction.

Previous wording

Our product candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, import and export are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by comparable foreign regulatory authorities. Before we can commercialize any of our product candidates, we must obtain regulatory approval. Although we received FDA clearance of five of our IND applications for each of TNG908, TNG462, TNG260, TNG348, and TNG456, we have since discontinued development in TNG348 and TNG908. We have not received approval to market any of our product candidates from regulatory authorities in any jurisdiction. It is possible that our product candidates, including any product candidates we may seek to develop in the future, will never obtain regulatory approval. We have limited experience in filing and supporting the applications necessary to gain regulatory approvals and expect to rely on third-party CROs and/or regulatory consultants to assist us in this process. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority. Our product candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended pharmacokinetics, side effects, toxicities or other characteristics that may preclude our obtaining regulatory approval or prevent or limit commercial use. In addition, regulatory authorities may find fault with our manufacturing process or facilities or that of third-party contract manufacturers. We and our third-party manufacturers that we expect to rely on for commercial production of our therapies, if approved, may also face greater than expected difficulty in manufacturing our product candidates.

Current wording

Our product candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, import and export are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by comparable foreign regulatory authorities. Before we can commercialize any of our product candidates, we must obtain regulatory approval. Although we received FDA clearance of five of our IND applications for each of TNG908, vopimetostat, TNG260, TNG348, and TNG456, we have since discontinued development in TNG348 and TNG908. We have not received approval to market any of our product candidates from regulatory authorities in any jurisdiction. It is possible that our product candidates, including any product candidates we may seek to develop in the future, will never obtain regulatory approval. We have limited experience in filing and supporting the applications necessary to gain regulatory approvals and expect to rely on third-party CROs and/or regulatory consultants to assist us in this process. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority. Our product candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended pharmacokinetics, side effects, toxicities or other characteristics that may preclude our obtaining regulatory approval or prevent or limit commercial use. In addition, regulatory authorities may find fault with our manufacturing process or facilities or that of third-party contract manufacturers. We and our third-party manufacturers that we expect to rely on for commercial production of our therapies, if approved, may also face greater than expected difficulty in manufacturing our product candidates.

Previous wording

The development and commercialization of new products in the biopharmaceutical and related industries is highly competitive. We compete in the segments of the pharmaceutical, biotechnology, and other related markets that address structural biology-guided chemistry-based drug design to develop therapies in the fields of cancer and genetic diseases. There are many other companies focusing on precision oncology to develop therapies in the fields of cancer and other diseases. Specifically, with respect to TNG462 and TNG456, we are aware that Bristol Myers Squibb (which acquired Mirati), Amgen, AstraZeneca, Beigene and Abbisko each have a clinical MTA-cooperative PRMT5 inhibitor program that have commenced clinical trials, using the same mechanism of action as TNG462 and TNG456. Other companies have announced PRMT5 inhibitor programs, including Gilead Sciences and IDEAYA Biosciences, and they may initiate clinical trials in the near future. Additionally, there are other indirect competitors running clinical trials in the PRMT5 inhibition space, including IDEAYA Biosciences, Beigene, Insilico Medicine and Servier Pharmaceuticals, which each have clinical MAT2A inhibitor programs.

Current wording

The development and commercialization of new products in the biopharmaceutical and related industries is highly competitive. We compete in the segments of the pharmaceutical, biotechnology, and other related markets that address structural biology-guided chemistry-based drug design to develop therapies in the fields of cancer and genetic diseases. There are many other companies focusing on precision oncology to develop therapies in the fields of cancer and other diseases. Specifically, with respect to vopimetostat and TNG456, we are aware that Bristol Myers Squibb (which acquired Mirati), Amgen, AstraZeneca, BeOne and Abbisko each have a clinical MTA-cooperative PRMT5 inhibitor program that have commenced clinical trials, using the same mechanism of action as vopimetostat and TNG456. Other companies have announced PRMT5 inhibitor programs, including Gilead Sciences and IDEAYA Biosciences, and they may initiate clinical trials in the near future. Additionally, there are other indirect competitors running clinical trials in the PRMT5 inhibition space, including IDEAYA Biosciences, BeOne, Insilico Medicine and Servier Pharmaceuticals, which each have clinical MAT2A inhibitor programs.

Previous wording

The incidence and prevalence for the target patient populations of our programs and product candidates have not been established with precision. TNG462 and TNG456 are both oral small molecule inhibitors of PRMT5. We are developing TNG462 for the treatment of patients with solid tumors with MTAP deletion, a genetic alteration that occurs in 10% to 15% of all human tumors, with a particular focus on pancreatic and lung cancer. Our next generation, brain-penetrant PRMT5 product candidate is TNG456. Since TNG456 crosses the blood-brain barrier in preclinical non-human primate models, we intend our development program to have a particular focus on patients with GBM. Additionally, 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 a genetic alteration in approximately 20% of lung, 15% of cervical, 10% carcinoma of unknown primary, 5% of breast and 3% of pancreatic cancers. Our projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are based on our and third parties' estimates.

Current wording

The incidence and prevalence for the target patient populations of our programs and product candidates have not been established with precision. Vopimetostat and TNG456 are both oral small molecule inhibitors of PRMT5. We are developing vopimetostat for the treatment of patients with solid tumors with MTAP deletion, a genetic alteration that occurs in 10% to 15% of all human tumors, with a particular focus on pancreatic and lung cancer. Our next generation, brain-penetrant PRMT5 product candidate is TNG456. Since TNG456 crosses the blood-brain barrier in preclinical non-human primate models, our development program has a particular focus on patients with GBM. Additionally, 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 a genetic alteration in approximately 20% of lung, 15% of cervical, 10% carcinoma of unknown primary, 5% of breast and 3% of pancreatic cancers. We are also currently or planning to run clinical trials of vopimetostat in combination with multiple different compounds, including RevMed’s RAS(ON) inhibitors and Erasca's pan-RAS molecular glue. Our projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are based on our and third parties' estimates.

Previous wording

We do not have the ability to independently conduct clinical trials. We currently rely, and expect to continue to rely, on medical institutions, clinical investigators, contract laboratories and other third parties, such as CROs, to conduct or otherwise support clinical trials for our product candidates, including our current and future Phase 1/2 clinical trials of TNG462, TNG260 and TNG456, and for any other product candidates that emerge from our precision oncology programs. We may also rely on academic and private non-academic institutions to conduct and sponsor clinical trials relating to our product candidates.

Current wording

We do not have the ability to independently conduct clinical trials. We currently rely, and expect to continue to rely, on medical institutions, clinical investigators, contract laboratories and other third parties, such as CROs, to conduct or otherwise support clinical trials for our product candidates, including our current and future Phase 1/2 clinical trials of vopimetostat (as a monotherapy and in combination), TNG260 and TNG456, and for any other product candidates that emerge from our precision oncology programs. We may also rely on academic and private non-academic institutions to conduct and sponsor clinical trials relating to our product candidates.

Previous wording

Since we rely on third parties for the execution of clinical trials for our product candidates, we control only certain aspects of their activities that will be important for the conduct of the trial (and such control that we do exercise may be based on contractual provisions that may be breached by the third-party). For example, for the Phase 1/2 clinical trials of TNG462, TNG456 and TNG260, we are and will rely on the same CRO for the conduct of each of these trials and, depending on the trial, one or a very limited number of manufacturers to manufacture the study drug to be used during the course of the trials. We are responsible for ensuring that each of our clinical trials is conducted and the applicable study drug is manufactured in accordance with the applicable protocol, legal and regulatory requirements and scientific standards, and our reliance on a CRO or CDMO will not relieve us of our regulatory responsibilities. For any violations of laws and regulations during the conduct of our clinical trials, we could be subject to warning letters or enforcement action that may include civil penalties, suspension/hold or termination of trials and other penalties up to and including criminal prosecution.

Current wording

Since we rely on third parties for the execution of clinical trials for our product candidates, we control only certain aspects of their activities that will be important for the conduct of the trial (and such control that we do exercise may be based on contractual provisions that may be breached by the third-party). For example, for the Phase 1/2 clinical trials of vopimetostat, TNG456 and TNG260, we are and will rely on the same CRO for the conduct of each of these trials and, depending on the trial, one or a very limited number of manufacturers to manufacture the study drug to be used during the course of the trials. We are responsible for ensuring that each of our clinical trials is conducted and the applicable study drug is manufactured in accordance with the applicable protocol, legal and regulatory requirements and scientific standards, and our reliance on a CRO or CDMO will not relieve us of our regulatory responsibilities. For any violations of laws and regulations during the conduct of our clinical trials, we could be subject to warning letters or enforcement action that may include civil penalties, suspension/hold or termination of trials and other penalties up to and including criminal prosecution.

Previous wording

Although we have designed all of our current Phase 1/2 clinical trials, the operational details of these trials will be executed by CROs, and we expect CROs will conduct all of our future clinical trials. As a result, many important aspects of our development programs, including their conduct and timing, are outside of our direct control. Our reliance on third parties to conduct future clinical trials also results in less direct control over the management of data developed through clinical trials than would be the case if we were relying entirely upon our own staff. Communicating with outside parties can also be challenging, potentially leading to mistakes as well as difficulties in coordinating activities. Outside parties may have staffing difficulties, fail to comply with contractual obligations, experience regulatory compliance issues, undergo changes in priorities or become financially distressed or form relationships with other entities, some of which may be our competitors.

Current wording

Although we have designed all of our current Phase 1/2 clinical trials and anticipate that we will design our pivotal trial, the operational details of these trials will be executed by CROs, and we expect CROs will conduct all of our future clinical trials. As a result, many important aspects of our development programs, including their conduct and timing, are outside of our direct control. Our reliance on third parties to conduct future clinical trials also results in less direct control over the management of data developed through clinical trials than would be the case if we were relying entirely upon our own staff. Communicating with outside parties can also be challenging, potentially leading to mistakes as well as difficulties in coordinating activities. Outside parties may have staffing difficulties, fail to comply with contractual obligations, experience regulatory compliance issues, undergo changes in priorities or become financially distressed or form relationships with other entities, some of which may be our competitors.

Previous wording

In addition, funding provided by a collaborator might not be sufficient to advance product candidates under the collaboration. For example, although Gilead provided us with $175.0 million upfront payments and a $20.0 million equity investment in connection with our collaboration, we might need additional funding to advance product candidates prior to the completion of the applicable milestones of the collaboration agreement with Gilead.

Current wording

In addition, funding provided by a collaborator might not be sufficient to advance product candidates under the collaboration. For example, although Gilead provided us with $175.0 million upfront payments and a $20.0 million equity investment in connection with our collaboration, we have since truncated the research term of this collaboration and anticipate that we will need additional funding to advance product candidates prior to receiving any milestones from the collaboration agreement with Gilead.

Previous wording

The API we use and that we may continue to use in all of our product candidates is supplied to us from one supplier. The drug product used in our product candidates is supplied by two manufacturers (and the manufacturer that produces the API is also one of the two suppliers of our the drug product used in our current clinical trials). Our ability to successfully develop our product candidates, and to ultimately supply our commercial products in quantities (if approved by regulatory authorities) sufficient to meet the market demand (and to meet requirements in connection with our ongoing and planned clinical trials), depends in part on our ability to obtain the API and drug product for these products in accordance with regulatory requirements and in sufficient quantities for clinical testing and commercialization, when applicable. We are also unable to predict how changing global economic conditions or global health concerns, as well as potential supply chain disruptions or cost increases related thereto, will affect our third-party suppliers and manufacturers. The risks related to global economic and political changes and supply chain disruption could have a material impact since one of our two CDMOs is located in China. Further, this CDMO, which is our sole supplier of API for the drugs used in our clinical trials, is affiliated with WuXi AppTec, and WuXi AppTec has been the subject of proposed Congressional legislation that, if enacted or if the subject of similar executive or administrative action, could restrict WuXi's business in the United States or the ability of businesses in the United States to conduct business with WuXi on national security grounds. We have started the process to locate an alternate producer of API, but there is no guarantee that we can identify and engage an alternate producer or manufacturer in time so as not to disrupt our clinical trials, on terms that are acceptable to us (including financial terms), or at all. Any negative impact of the ability of our CDMOs to deliver API and/or drug product due to political actions, supply chain disruptions or otherwise, may have a material adverse impact on our results of operations or financial condition.

Current wording

The API we use and that we may continue to use in all of our product candidates is supplied to us from one supplier. The drug product used in our product candidates is supplied by two manufacturers (and the manufacturer that produces the API is also one of the two suppliers of the drug product used in our current clinical trials). Our ability to successfully develop our product candidates, and to ultimately supply our commercial products in quantities (if approved by regulatory authorities) sufficient to meet the market demand (and to meet requirements in connection with our ongoing and planned clinical trials), depends in part on our ability to obtain the API and drug product for these products in accordance with regulatory requirements and in sufficient quantities for clinical testing and commercialization, when applicable. We are also unable to predict how changing global economic conditions or global health concerns, as well as potential supply chain disruptions or cost increases related thereto, will affect our third-party suppliers and manufacturers. The risks related to global economic and political changes and supply chain disruption could have a material impact since one of our two CDMOs is located in China.

Previous wording

Even if a patent is issued, that is not conclusive as to its inventorship, scope, validity or enforceability and therefore that patent may not afford adequate (or any) protection for our product candidates or future approved products or technology. On the basis of such inconclusiveness, third parties may challenge our patents. Furthermore, patents have a limited lifespan. In the United States and most other jurisdictions in which we have undertaken patent filings, the natural expiration of a patent is generally twenty years after it is filed, assuming all maintenance fees are paid. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, patents we may own or in-license may not provide us with adequate and continuing patent protection sufficient to exclude others from commercializing drugs similar or identical to our current or future product candidates, including generic versions of our drugs. Nor can we be certain that we will obtain any patent term extension as permitted under the “Hatch-Waxman Amendments” which permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.

Current wording

Even if a patent is issued, that is not conclusive as to its inventorship, scope, validity or enforceability and therefore that patent may not afford adequate (or any) protection for our product candidates or future approved products or technology. On the basis of such inconclusiveness, third parties may challenge our patents. Furthermore, patents have a limited lifespan. In the United States and most other jurisdictions in which we have undertaken patent filings, the natural expiration of a patent is generally twenty years after it is filed, assuming all maintenance fees are paid. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. Delays in our clinical trials or regulatory approval process may further reduce the effective patent protection period for our products, as patents generally expire 20 years from their earliest filing date regardless of when regulatory approval is obtained. As a result, patents we may own or in-license may not provide us with adequate and continuing patent protection sufficient to exclude others from commercializing drugs similar or identical to our current or future product candidates, including generic versions of our drugs. Nor can we be certain that we will obtain any patent term extension as permitted under the “Hatch-Waxman Amendments” which permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.

Previous wording

Other parties have developed technologies that may be related or competitive to our own, and such parties may have filed or may file patent applications, or may have received or may receive patents, claiming inventions that may overlap or conflict with those claimed in our own patent applications or issued patents, with respect to either the same compounds, methods, formulations or other subject matter, in either case that we may rely upon to dominate our patent position in the market. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until at least 18 months after the earliest priority date of patent filing, or, in some cases, not at all. Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in patents we may own or in-license patents or pending patent applications, or that we were the first to file for patent protection of such inventions. As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights cannot be predicted with any certainty.

Current wording

Other parties have developed technologies that may be related or competitive to our own, and such parties may have filed or may file patent applications, or may have received or may receive patents, claiming inventions that may overlap or conflict with those claimed in our own patent applications or issued patents, with respect to either the same compounds, methods, formulations or other subject matter, in either case that we may rely upon to dominate our patent position in the market. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until at least 18 months after the earliest priority date of patent filing, or, in some cases, not at all. Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in patents we may own or in-license patents or pending patent applications, or that we were the first to file for patent protection of such inventions. As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights cannot be predicted with any certainty. Additionally, obtaining broad patent protection for certain method-of-use claims and combination therapies may be challenging due to the existing body of scientific knowledge in these areas, and any patents that do issue may be subject to challenge or may be designed around by competitors.

Previous wording

In some instances, we believe we may prevail in a patent infringement action. There can, however, be no assurance that the court will agree with our position or that it will decide any infringement case in our favor. Nor can we be certain that, if we do not prevail in litigation, that we may be able to obtain a license to any third-party patent on commercially reasonable terms (or at all); successfully develop non-infringing alternatives on a timely basis (or at all); or license alternative non-infringing technology, if any exists, on commercially reasonable terms (or at all). Any impediment to our ability to manufacture, use or sell approved forms of our future products (if approved by regulatory authorities) or our product candidates could have a material adverse effect on our business and prospects.

Current wording

In some instances, we believe we may prevail in a patent infringement action. There can, however, be no assurance that the court will agree with our position or that it will decide any infringement case in our favor. Nor can we be certain that, if we do not prevail in litigation, we may be able to obtain a license to any third-party patent on commercially reasonable terms (or at all); successfully develop non-infringing alternatives on a timely basis (or at all); or license alternative non-infringing technology, if any exists, on commercially reasonable terms (or at all). Any impediment to our ability to manufacture, use or sell approved forms of our future products (if approved by regulatory authorities) or our product candidates could have a material adverse effect on our business and prospects.

Previous wording

a court prohibiting us from developing, manufacturing, marketing or selling our current product candidates, including TNG462, TNG456 or TNG260 or future product candidates, or from using our proprietary technologies, unless the third party licenses its product, process or other rights to us, which it is not required to do, on commercially reasonable terms or at all;

Current wording

a court prohibiting us from developing, manufacturing, marketing or selling our current product candidates, including vopimetostat, TNG456 or TNG260 or future product candidates, or from using our proprietary technologies, unless the third party licenses its product, process or other rights to us, which it is not required to do, on commercially reasonable terms or at all;

Previous wording

If the FDA determines that a product candidate offers a treatment for a serious condition and, if approved, the product would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A priority review designation means that the goal for the FDA to review an application is six months from the date of filing, rather than the standard review period of ten months from the date of filing. We may request priority review for our product candidates. The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a priority review designation does not necessarily result in an expedited regulatory review or approval process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures. Receiving priority review from the FDA does not guarantee approval within the six-month review cycle or at all.

Current wording

If the FDA determines that a product candidate offers a treatment for a serious or life-threatening condition and, if approved, the product would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A priority review designation means that the goal for the FDA to review an application is six months from the date of filing, rather than the standard review period of ten months from the date of filing. We may request priority review for our product candidates. The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a priority review designation does not necessarily result in an expedited regulatory review or approval process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures. Receiving priority review from the FDA does not guarantee approval within the six-month review cycle or at all.

Previous wording

As part of our business strategy, we may seek orphan drug designation for certain of our product candidates, and we may be unsuccessful in obtaining such designation. Regulatory authorities in some jurisdictions, including the United States and Europe, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a drug as an orphan drug if it is a product intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States, or a patient population of 200,000 or more in the United States where there is no reasonable expectation that the cost of developing the product will be recovered from sales in the United States. In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. The FDA granted Orphan Drug Designation to TNG462 for the treatment of soft tissue sarcoma and of pancreatic cancer.

Current wording

As part of our business strategy, we may seek orphan drug designation for certain of our product candidates, and we may be unsuccessful in obtaining such designation. Regulatory authorities in some jurisdictions, including the United States and Europe, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a drug as an orphan drug if it is a product intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States, or a patient population of

Previous wording

We may seek a breakthrough therapy designation for some of our product candidates. A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug or biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For product candidates that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Product candidates designated as breakthrough therapies by the FDA may also be eligible for priority review and accelerated approval. Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. In any event, the receipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to therapies considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that such product candidates no longer meet the conditions for qualification and rescind the designation or decide that the time period for FDA review or approval will not be shortened.

Current wording

We may seek a breakthrough therapy designation for some of our product candidates. A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For product candidates that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Product candidates designated as breakthrough therapies by the FDA may also be eligible for rolling review, priority review and accelerated approval. Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. In any event, the receipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to therapies considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that such product candidates no longer meet the conditions for qualification and rescind the designation or decide that the time period for FDA review or approval will not be shortened.