TYRA 10-K & 10-Q changes, risk factors and insider trading

We intend to rely on third parties for the manufacture of our product candidates for preclinical and clinical development. This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.

We have incurred significant operating losses since our inception. Our net losses were $86.5$119.9 million and $69.1$86.5 million for the years ended December 31, 20242025 and 2023,2024, respectively. As of December 31, 2024,2025, we had an accumulated deficit of $251.3$371.3 million. Substantially all of our losses have resulted from expenses incurred in connection with our research and development programs and from general and administrative costs associated with our operations. TYRA-300,Dabogratinib TYRA-200,(formerly TYRA-430TYRA-300), TYRA-430, TYRA-200 and any of our other product candidates will require substantial additional development time and resources before we are able to apply for, or receive, marketing approval and begin generating revenue from product sales. We expect to continue to incur losses for the foreseeable future, and we anticipate these losses will increase substantially as we continue our development of, and seek marketing approval for, and potentially commercialize any of our product candidates and as we seek to discover, develop and market additional potential product candidates.

Based upon our current operating plan, we believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operations through at least 2027. We have based these estimates on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect. Our operating plans and other demands on our cash resources may change as a result of many factors currently unknown to us, and we may need to seek additional funds sooner than planned, through public or private equity or debt financings or other capital sources, including potentially additional collaborations, licenses and other similar arrangements. In addition, we may seek additional capital due to favorable market conditions or liquidity or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. For example, in OctoberMay 2022,2025, we entered into an ATMa Sales Agreement (the Sales Agreement) with VirtuTD AmericasSecurities (USA) LLC (the Agent), pursuant to which we may, from time to time, sell shares of our common stock having an aggregate offering price of up to $150 million in “at the market” offerings through or to the Agent, as sales agent or principal. However, there can be no assurance that the Agent will be successful in consummating any future sales based on prevailing market conditions or in the quantities or at the prices that we deem appropriate. In addition, the Sales Agreement may be terminated by us or the Agent at any time upon specified notice to the other party, or by the Agent at any time in certain circumstances, including the occurrence of a material adverse change. Attempting to secure additional financing may divert our management from our day-to-day activities, which may adversely affect our ability to develop our product candidates.

The value of our investments may decline due to increases in interest rates, downgrades of the bonds and other securities included in our commercial money market account portfolio and instability in the global financial markets that reduces the liquidity of securities included in our portfolio. In addition, in the past, the closure of financial institutions and their placement into receivership with the Federal Deposit Insurance Corporation (FDIC) created bank-specific and broader financial institution liquidity risk and concerns. Future adverse developments with respect to specific financial institutions or the broader financial services industry may impair our ability to access capital needed to support near-term working capital needs, whether from our existing investment and deposit accounts and credit facilities or otherwise, and may lead to market-wide liquidity shortages and create additional market and economic uncertainty. Furthermore, possiblefrom time to time recession and rising inflation concerns have adversely affected and may continuein tothe future adversely affect the financial markets in some or all countries worldwide. Each of these events may cause us to record charges to reduce the carrying value of our investment portfolio or sell investments for less than our acquisition cost. Although we attempt to mitigate these risks through diversification of our investments, the value of our investments may nevertheless decline, and our ability to fund our near-term and long-term working capital needs to support our business and clinical development plans may be adversely affected. In addition, any decline in available funding or access to our cash and liquidity resources could also result in breaches of our financial and/or contractual obligations or result in violations of federal or state wage and hour laws.

We are in the early stages of our research andclinical development effortsefforts. and allAll of our development programs are either in early clinical development or the preclinical or drug discovery stage. We have invested substantially all of our efforts to date in developing our proprietary SNÅP platform, developing TYRA-300,dabogratinib, TYRA-200TYRA-430 and TYRA-430,TYRA-200, identifying other potential product candidates and conducting preclinical studies.studies and clinical trials. We are relatively early in our clinical trials of our product candidates and will need to progress our other development programs through additional preclinical studies to enable us to submit INDs with the FDA and receive allowance from the FDA to proceed with initiating their clinical development. Our ability to generate product revenues, which we do not expect will occur for many years, if ever, will depend on the successful development and eventual commercialization of our product candidates. The success of our product candidates will depend on several factors, including the following:

The FDA or comparable foreign regulatory authorities can refuse to accept INDs or similar regulatory submissions for many reasons, including negative or ambiguous results from our preclinical studies or disagreement with our interpretation of data from preclinical studies. If we are unable to develop, obtain marketing approval for, or, if approved, successfully commercialize our product candidates, we may not be able to generate sufficient revenue to continue our business.

We are relatively early in our development efforts for our product candidates and we will need to successfully complete our ongoing and planned clinical trials and later-stage and pivotal clinical trials, in order to obtain marketing authorization from the FDA or comparable foreign regulatory authorities to market TYRA-300,our TYRA-200,product TYRA-430,candidates, as well as complete IND-enabling studies for our development programs in the preclinical or discovery stage. Carrying out clinical trials and the submission of a successful NDA is a complicated process. As an organization, while we have commenced clinical trials for certain of our product candidates, we have not previously completed any clinical trials, have limited experience as a company in preparing and submitting marketing applications and have not previously submitted an NDA or other comparable foreign regulatory submission for any product candidate. In addition, we have had limited interactions with the FDA and cannot be certain how many clinical trials of TYRA-300,dabogratinib, TYRA-200,TYRA-430, TYRA-430TYRA-200 or any other product candidates will be required or how such trials should be designed. Consequently, we may be unable to successfully and efficiently execute and complete necessary clinical trials in a way that leads to regulatory submission and approval of any of our product candidates. We may require more time and incur greater costs than our competitors and may not succeed in obtaining marketing approvals of product candidates that we develop. Failure to commence or complete, or delays in, our ongoing or planned clinical trials, could prevent us from, or delay us in submitting NDAs for, and commercializing our product candidates.

PreclinicalClinical and clinicalpreclinical development involves a lengthy and expensive process with an uncertain outcome, and the results of preclinical studies and early clinical trials are not necessarily predictive of future results. Our product candidates may not have favorable results in clinical trials, if any, or receive marketing approval on a timely basis, if at all.

PreclinicalClinical and clinicalpreclinical development is expensive and can take many years to complete, and its outcome is inherently uncertain. We cannot guarantee that any clinical trials or preclinical studies or clinical trials will be conducted as planned or completed on schedule, if at all, and delay or failure can occur at any time during the preclinical study or clinical trial process, including due to factors that are beyond our control. Further, we may not be able to meet expected timeframes for data readouts. Despite promising preclinical or clinical results, any biopharmaceutical company’s product candidate can unexpectedly fail at any stage of preclinical or clinical development, and regulators, such as the FDA or comparable foreign regulatory authorities, may not accept the results as demonstrating the product candidate’s safety and efficacy. The historical failure rate for product candidates in our industry is high.

The results from preclinical studies or clinical trials of a product candidate may not predict the results of later clinical trials of the product candidate, and interim, topline, or preliminary results of a clinical trial are not necessarily indicative of final results. Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy characteristics despite having progressed through preclinical studies and initial clinical trials. In particular, while we have conducted certain preclinical studies of our product candidates , we do not know whether our current product candidates or other potential product candidates will perform in current or future clinical trials as they have performed in these prior studies. The positive results we have observed for our product candidates in preclinical animal models may not be predictive of our current or future clinical trials in humans. In addition, while we have previously reported interim results from our ongoing SURF301clinical trial,trials theyand may do so in the future, such results are not necessarily indicative of final results or results from future trials,trials. It is not uncommon to observe results in clinical trials that are unexpected based on preclinical studies and early clinical trials, and many product candidates fail in clinical trials despite very promising early results. If unexpected observations or toxicities are observed in our ongoing or planned trials, or in IND-enabling studies for any of our otherfuture product candidates, such results could delay and possibly prevent or limit clinical trials for our product candidates. Moreover, preclinical and clinical data may be susceptible to varying interpretations and analyses. A number of companies in the biopharmaceutical and biotechnology industries have suffered significant setbacks in clinical development even after achieving promising results in earlier studies. Such setbacks have occurred and may occur for many reasons, including, but not limited to: clinical sites and investigators may deviate from clinical trial protocols, whether due to lack of training or otherwise, and we may fail to detect any such deviations in a timely manner; patients may fail to adhere to any required clinical trial procedures, including any requirements for post-treatment follow-up; our product candidates may fail to demonstrate effectiveness or safety in certain patient subpopulations, which has not been observed in earlier trials due to limited sample size, lack of analysis or otherwise; or our clinical trials may not adequately represent the patient populations we intend to treat, whether due to limitations in our trial designs or otherwise, such as where one patient subgroup is overrepresented in the clinical trial. There can be no assurance that we will not suffer similar setbacks despite the data we observed in earlier or ongoing studies. Based upon negative or inconclusive results, we or any future collaborator may decide, or regulators may require us, to conduct additional preclinical studies or clinical trials, which would cause us to incur additional operating expenses and delays and may not be sufficient to support regulatory approval on a timely basis or at all.

For the foregoing reasons, we cannot be certain that our ongoing and planned clinical trials and preclinical studies and clinical trials will be successful. In addition, any safety concerns observed in any one of our clinical trials in our targeted indications could impair the development, marketing approval or commercial prospects of our product candidates in those and other targeted indications, such as TYRA-300dabogratinib for oncology and achondroplasia,ACH, which could have a material adverse effect on our business, financial condition and results of operations.

The discovery and development of targeted therapeutics for patients with genomically defined cancers is an emerging field, and the scientific discoveries that form the basis for our efforts to discover and develop product candidates are relatively new. Although we believe, based on our preclinical work in oncology, that the genomic alterations targeted by our programs are oncogenic drivers, clinical results may not confirm this hypothesis or may only confirm it for certain alterations or certain tumor types. In addition, even if our approach is successful in showing clinical benefit for acquired resistance mutation-driven cancers for our TYRA-300,dabogratinib, TYRA-200,TYRA-430 or TYRA-430TYRA-200 product candidates, we may never successfully identify additional oncogenic alterations for other receptor tyrosine kinases using our SNÅP platform, or succeed in identifying additional product candidates to address such alterations. Any product candidates we do discover and advance based on scientific approach may be later shown to have harmful side effects or may have other characteristics that may necessitate additional clinical testing, or make the product candidates unmarketable or unlikely to receive marketing approval. Therefore, we do not know if our approach of discovering and developing product candidates to treat patients with genomically defined cancers will be successful, and if our approach is unsuccessful, we may be forced to abandon our development efforts for a program or programs, which would have a material adverse effect on our business and could potentially cause us to cease operation.

Before we can initiate clinical trials for our product candidates, we must submit the results of preclinical studies to the FDA or comparable foreign regulatory authorities along with other information, including information about product candidate chemistry, manufacturing and controls and our proposed clinical trial protocol, as part of an IND or similar regulatory filing required for regulatory allowance before proceeding with clinical development. The FDA or comparable foreign regulatory authorities may require us to conduct additional preclinical studies for any product candidate before it allows us to initiate clinical trials under any IND or similar regulatory filing, which may lead to delays and increase the costs of our preclinical development programs. Moreover, even if these trials begin, issues may arise that could cause regulatory authorities to suspend or terminate such clinical trials. Any such delays in the commencement or completion of our ongoing or planned clinical trials for TYRA-300,dabogratinib, TYRA-200,TYRA-430, TYRA-430TYRA-200 or any other product candidate, could significantly affect our product development timelines and development costs.

The success of our business depends primarily upon our ability to identify, develop and commercialize products based on our proprietary SNÅP platform, which is designed to efficiently identify and selectively target vulnerabilities in the mutant proteins that commonly eliminate or reduce the effectiveness of standard-of-care therapies. We have not yet succeeded and may not succeed in demonstrating efficacy and safety for any product candidates in clinical trials or in obtaining marketing approval thereafter. Our product candidates are in the early stages of development and weWe have not yet completed any clinical trials for any product candidate. Our SNÅP platform utilizes the rapid generation of precise molecular SNÅPshots to continually gain deeper insights into the structure of inhibitor binding sites and how commonly occurring resistance mutations lead to acquired drug resistance to existing therapies, which we believe aids in the prediction of amino acid residues most likely to cause resistance to specific existing therapies. This innovative process may never be successful in identifying additional product candidates with innovative structures that are able to inhibit the target while avoiding those specific residues. Further, because all of our product candidates and discovery programs are based on our SNÅP platform, adverse developments with respect to one of our programs may have a significant adverse impact on the actual or perceived likelihood of success and value of our other development programs.

The timing of our clinical trials depends, in part, on the speed at which we can recruit patients to participate in our trials, as well as completion of required follow-up periods. The eligibility criteria of our clinical trials, once established, will further limit the pool of available trial participants. If patients are unwilling to participate in our trials for any reason, including the existence of concurrent clinical trials for similar patient populations or the availability of other therapies, or we otherwise have difficulty enrolling a sufficient number of patients, the timeline for recruiting patients, conducting clinical trials and obtaining marketing approval of our product candidates may be delayed. Additionally, because some of our initial clinical trials in oncology will be in patients with relapsed/refractory cancer, these patients are typically in the late stages of their disease and may experience disease progression independent from our product candidates, making them unevaluable for purposes of the clinical trial and requiring additional patient enrollment. Our inability to enroll a sufficient number of patients for any of our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether. In addition, we expect to rely on CROs and clinical trial sites to ensure proper and timely conduct of our clinical trials and, while we intend to enter into agreements governing their services, we will have limited influence over their actual performance.

Indeed, approval, certification or clearance of companion diagnostics may be subject to further legislative or regulatory reforms notably in the EU.EU, where it continues to undergo legislative changes. On May 25, 2017, the new In Vitro Medical Devices Regulation (IVDR) entered into force. The IVDR repeals and replaces the EU In Vitro Diagnostic Medical Devices Directive. Unlike directives, which must be implemented into the national laws of the EU member states, regulations are directly applicable, i.e., without the need for adoption of EU member states laws implementing them, in all EU member states and are intended to eliminate current differences in the regulation of medical devices among EU member states. The IVDR, among other things, is intended to establish a uniform, transparent, predictable and sustainable regulatory framework across the EU for medical devices and ensure a high level of safety and health while supporting innovation. The IVDR became applicable on May 26, 2022. Following subsequent legislative changes, European institutions adopted a “progressive” roll-out of the IVDR to prevent disruption in the supply of in vitro diagnostic medical devices. Therefore, the IVDR applies since May 26, 2022, but there is a tiered system extending the grace period for many devices (depending on their risk classification) before they have to be fully compliant with the regulation.

We have received orphan drug designation from the FDA for TYRA-300dabogratinib for the treatment of ACH, and we may seek additional orphan drug designations in the United States and/or the EU for TYRA-300dabogratinib and our other product candidates in qualified patient populations. There can be no assurance that the FDA or European Commission will grant orphan designation for any indication for which we apply, or that we will be able to maintain such designation.

In the United States, orphan designation entitles a party to financial incentives such as opportunities for grant funding toward clinical trial costs, tax advantages and user-fee waivers. In addition, if a product candidate that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including an NDA, to market the same product for the same approved indication or use within such disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity in the relevant indication or use, or where the manufacturer is unable to assure sufficient product quantity. In the EU, orphan designation entitles a party to financial incentives such as reduction of fees, fee waivers, protocol assistance, and access to the centralized marketing authorization procedure. Moreover, upon grant of a marketing authorization and assuming the requirement for orphan designation are also met at the time the marketing authorization is granted, orphan medicinal products are entitled to a ten-year period of market exclusivity for the approved therapeutic indication. The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed Pediatric Investigation Plan. The European exclusivity period can be reduced to six years, if, at the end of the fifth year a drug no longer meets the criteria for orphan designation (i.e. the prevalence of the condition has increased above the orphan designation threshold or it is judged that the product is sufficiently profitable so as not to justify maintenance of market exclusivity).

Even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs can be approved for the same indications or uses within the same disease or condition. Even after an orphan drug is approved, the FDA or comparable foreign regulatory authorities can subsequently approve the same drug for the same disease or condition if such regulatory authority concludes that the later drug is clinically superior within the relevant indication because it is shown to be safer, more effective or makes a major contribution to patient care. Orphan drug exclusivity may also be lost if the FDA later determines that the initial request for designation was materially defective. In addition, orphan drug exclusivity does not prevent the FDA from approving competing drugs containing a different active ingredient for the same or similar indication or use within the relevant disease or condition containing a different active ingredient.condition. In addition, if a subsequent drug is approved for marketing for the same or a similar diseaseindication or conditionuse as any of our product candidates that receive marketing approval, we may face increased competition and lose market share regardless of orphan drug exclusivity. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process.

We have obtained a rare pediatric disease designation for TYRA-300dabogratinib for the treatment of ACH, however, there is no guarantee that any FDA approval of TYRA-300dabogratinib will result in issuance of a priority review voucher.

We have obtained a RPD designation for TYRA-300dabogratinib for the treatment of ACH, however, there is no guarantee that we will be able to obtain a priority review voucher, even if TYRA-300dabogratinib is approved by the FDA for use in ACH patients. For example, the FDA may determine that an NDA, even if ultimately approved, does not meet the eligibility criteria for a priority review voucher, including for the following reasons:

the application does not rely on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population; or the application is approved for a different adult indication than the RPD for which the product is designated Moreover, Congress included a sunset provision in the statute authorizing the RPD priority review voucher program. Under the current statutory sunset provisions, afterprovided Septemberthe 30,eligibility 2024,criteria are otherwise met, the FDA may only award a voucher for an approved RPD product application if the sponsor has RPD designation for the product candidate,candidate and thatthe designationproduct wascandidate grantedis approved by DecemberSeptember 20,30, 2024.2029. After September 30, 2026,2029, the FDA may not award anya RPDvoucher, priorityregardless reviewof vouchers.an existing designation.

From time to time, we may publicly disclose preliminary, interim or topline data from our preclinical studies and clinical trials, such as the interim data we reported regarding the SURF301 trial in October 2024.trials. These interim updates are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial. For example, we may report responses in certain patients that are unconfirmed at the time and which do not ultimately result in confirmed responses to treatment after follow-up evaluations. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data. As a result, the topline results that we report may differ from future results of the same studies or trials, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, topline data should be viewed with caution until the final data are available. In addition, we may report interim analyses of only certain endpoints rather than all endpoints. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Adverse changes between interim data and final data could significantly harm our business and prospects. Further, additional disclosure of interim data by us or by our competitors in the future could result in volatility in the price of our common stock.

The accelerated approval pathway may be used in cases in which the advantage of a new drug over available therapy may not be a direct therapeutic advantage, but is a clinically important improvement from a patient and public health perspective. If granted, accelerated approval is usually contingent on the sponsor’s agreement to conduct, in a diligent manner, additional confirmatory studies to verify and describe the drug’s clinical benefit. If such post-approval studies fail to confirm the drug’s clinical benefit or are not completed in a timely manner, the FDA may withdraw its approval of the drug on an expedited basis. In addition, in December 2022, President Biden signed an omnibus appropriations bill to fund the U.S. government through fiscal year 2023. Included in the omnibus bill is the Food and Drug Omnibus Reform Act of 2022, which among other things,2022 provided the FDA newfurther statutory authority to mitigate potential risks to patients from continued marketing of ineffective drugs previously granted accelerated approval. Under these provisions, the FDA may require a sponsor of a product seeking accelerated approval to have a confirmatory trial underway prior to such approval being granted. In December 2024, the FDA further issued draft guidance for industry regarding the accelerated approval of drugs and biologics, which among other things, set forth the FDA’s current expectations for accelerated approval endpoints and confirmatory trials as well as the process for withdrawing accelerated approval.approval and in January 2025, the FDA issued draft guidance intended to clarify when a confirmatory trial may be considered underway. The FDA may continue to develop guidance or otherwise change its policies with respect to the accelerated approval pathway that may make it more difficult to seek accelerated approval of any of our product candidates.

Disruptions at the FDA and other government agencies caused by funding shortagesshortages, staffing limitations or globalpolicy health concernschanges could hinder their ability to hire, retain or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.

The ability of the FDA and comparable foreign regulatory activities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory and policy changes, the FDA’s and comparable foreign regulatory activities’ ability to hire and retain key personnel and accept the payment of user fees, and other events that may otherwise affect the FDA’s and comparable foreign regulatory activities’ ability to perform routine functions. Average review times at the FDA and comparable foreign regulatory activities have fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and comparable foreign regulatory activities may also slow the time necessary for new drugs and biologics or modifications to approved drugs and biologics to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, in recent years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA employees and stop critical activities. In addition, the current U.S. Presidential administration has issued certain policies and Executive Orders directed towards reducing the employee headcount and costs associated with U.S. administrative agencies, including the FDA, and it remains unclear the degree to which these efforts may limit or otherwise adversely affect the FDA’s ability to conduct routine activities.

If a prolonged government shutdown occurs, or if globalfunding healthshortages, concernsstaffing limitations or similar factors hinder or prevent the FDA or other regulatory authorities from conducting their regular inspections, reviewsreviews, or other regulatory activities, itsuch events could significantly impact the ability of the FDA or comparableother foreignsuch regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

We intend to rely on third parties for the manufacture of our product candidates for preclinical and clinical development. This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.

We do not own or operate manufacturing facilities and have no plans to develop our own clinical or commercial-scale manufacturing capabilities. We plan to rely, and expect to continue to rely, on third parties for the manufacture of our product candidates and related raw materials for preclinical and clinical development, as well as for commercial manufacture if any of our product candidates receive marketing approval. The facilities used by third-party manufacturers to manufacture our product candidates must be approved by the FDA or comparable foreign regulatory authorities for the manufacture of our product candidates pursuant to inspections that will be conducted after we submit an NDA to the FDA or any comparable filing to a foreign regulatory authority. We do not control the manufacturing process of, and are completely dependent on, third-party manufacturers for compliance with cGMP or similar foreign requirements for manufacture of products. If these third-party manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or any comparable foreign regulatory authority, they will not be able to secure and/or maintain marketing approval for their manufacturing facilities. In addition, we have no control over the ability of third-party manufacturers to maintain adequate quality control, quality assurance, qualified personnel, and accurate and complete recordkeeping. If the FDA or comparable foreign regulatory authorities does not approve these facilities for the manufacture of our product candidates or if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain marketing approval for or market our product candidates, if approved. Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us or the third-party manufacturers, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products.

In addition, we currently and may in the future rely on contract manufacturers in China. Such foreign contract manufacturers may be subject to U.S. legislation, sanctions, tariffs, trade restrictions and other foreign regulatory requirements which could increase the cost or reduce the supply of material available to us, delay the procurement or supply of such material or have an adverse effect on our ability to secure significant commitments from governments to purchase our potential therapies. For example, inthe JanuaryU.S. 2024,BIOSECURE thereAct, which was Congressionalenacted activity,in includingDecember 2025, prohibits federal agencies from procuring or using any biotechnology equipment or services from “biotechnology companies of concern”, or entering into, extending, or renewing any contracts with entities that use such biotechnology equipment or services from “biotechnology companies of concern”. Congress has interpreted a “biotechnology company of concern” as an entity that is under the introductioncontrol of a foreign adversary and that poses a risk to national security based on its research or multiomic data collection (e.g., collection of genomic information). While the U.S. BIOSECURE Act has a grandfathering period of five years for existing contracts, and has carveouts for manufacture of drugs for supply under Medicaid and Medicare Part B, subject to the Secretary of Veteran Affairs’ discretion, the impact of the BIOSECURE Act (H.R. 7085) in the House of Representatives and a substantially similar Senate bill (S.3558). TheU.S. BIOSECURE Act was passed byon the Housebiotechnology ofindustry Representativesis inuncertain. SeptemberThis 2024. If these bills orand similar laws become law, they could have the potential to materially restrict the ability of U.S. biopharmaceutical companies like us to purchase services or products fromfrom, or otherwise collaborate with, certain Chinese biotechnology companies “of concern” without losing the ability to contract with, or otherwise receive funding from, the U.S. government.

The availability ofAdequate coverage and the adequacy of reimbursement by governmental healthcare programs such as Medicare and Medicaid, private health insurers and other third-party payors are essential for most patients to be able to afford prescription medications such as our product candidates, if approved. Our ability to achieve coverage and acceptable levels of reimbursement for our products by third-party payors will have an effect on our ability to successfully commercialize those products. Moreover, we are initially developing TYRA-300dabogratinib for the treatment of mUC, pediatric ACHACH, NMIBC and NMIBC, TYRA-200 for FGFR2-driven ICC resistant to previous FGFR inhibitors andLG-UTUC, TYRA-430 for advanced HCC and other solid tumors with activating FGF/FGFR pathway aberrations.aberrations, and TYRA-200 for FGFR2-driven ICC resistant to previous FGFR inhibitors. Some of these indications target a small patient population. In order for products that are designed to treat smaller patient populations to be commercially viable, the reimbursement for such products must be higher, on a relative basis, to account for the lack of volume. Accordingly, we will need to implement a coverage and reimbursement strategy for any approved product candidate with a smaller patient population that accounts for the smaller potential market size. Even if we obtain coverage for a given product by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high. For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization. We cannot be sure that coverage and reimbursement in the United States, the EU or elsewhere will be available for any product that we may develop, and any reimbursement that may become available may be decreased or eliminated in the future.

We expect to face competition from existing products and products in development for each of our product candidates. There are three currently marketed pan-FGFR inhibitors: Incyte Corporation’s Pemazyre (pemigatinib), Taiho’s Lytgobi (futibatinib) approved in FGFR2 gene rearrangements in cholangiocarcinoma, and Janssen Biotech, Inc.’s Balversa (erdafitinib), approved in specific FGFR3 gene alterations. There are a number of other isoform-specific FGFR inhibitors such as Elevar Therapeutics’ and Relay Therapeutics, Inc.’s lirafugratinib (RLY-4008), Cogent Biosciences’ CGT4859, TransThera’s tinengotinib and Lilly’s Loxo Oncology’s isoform-selective FGFR3 inhibitor compound, LOXO-435 (LOX-24350). There are currently no approved FGFR4 inhibitors, but there remain a number of FGFR4 programs in clinical development in China, including Abbisko’s ABSK011. BioMarin Pharmaceutical’s Voxzogo, a once daily injectable C-natriuretic peptide (CNP) analog isand Ascendis’ CNP pro-drug (TransCon CNP) are approved in the United States for children with ACH. There are a number of other experimental therapies in development for ACH, including Ascendis’ CNP pro-drug (TransCon CNP) and QED Therapeutics’ low dose pan-FGFR inhibitor (infigratinib).

The precise incidence and prevalence for all the diseases or conditions we aim to address with our product candidates are unknown. Our projections of both the number of people who have these diseases,diseases or conditions, as well as the subset of people with these diseases or conditions who have the potential to benefit from treatment with our product candidates, are based on our beliefs and estimates. These estimates have been derived from a variety of sources, including the scientific literature, surveys of clinics, patient foundations or market research, and may prove to be incorrect. Further, new trials may change the estimated incidence or prevalence of these indications. The total addressable market across all of our product candidates will ultimately depend upon, among other things, the diagnosis criteria included in the final label for each of our product candidates which receives marketing approval for these indications, the availability of alternative treatments and the safety, convenience, cost and efficacy of our product candidates relative to such alternative treatments, acceptance by the medical community and patient access, drug pricing and reimbursement. The number of patients in the United States and other major markets and elsewhere may turn out to be lower than expected, patients may not be otherwise amenable to treatment with our product candidates or new patients may become increasingly difficult to identify or gain access to, all of which would adversely affect our results of operations and our business. Further, even if we obtain significant market share for our product candidates, because some of our potential target populations are very small, we may never achieve profitability despite obtaining such significant market share.

As of MarchFebruary 25, 2025,2026, we had 6087 full-time employees , including 4467 employees engaged in research and development. In order to successfully implement our development and commercialization plans and strategies, we expect to need to continue to add significant additional managerial, operational, sales, marketing, financial and other personnel. Future growth will impose significant added responsibilities on members of management, including:

In addition, certain state laws and regulations govern the privacy, processing and security of health-related and other personal information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts. By way of example, the California Consumer Privacy Act, as amended by the California Privacy Rights Act (collectively, the CCPA) requires covered businesses that process the personal information of California residents to, among other things: (i) provide certain disclosures to California residents regarding the business’s collection, use, and disclosure of their personal information; (ii) receive and respond to requests from California residents to access, delete, and correct their personal information, or to opt out of certain disclosures of their personal information; and (iii) enter into specific contractual provisions with service providers that process California resident personal information on the business’s behalf. Additional compliance investment and potential business process changes may be required. Similar laws have passed in other states and are continuing to be proposed at the state and federal level,states, reflecting a trend toward more stringent privacy legislation in the United States. The enactment of such laws could have potentially conflicting requirements that would make compliance challenging. In the event that we are subject to or affected by HIPAA, the CCPA or other domestic privacy and data protection laws, any liability from failure to comply with the requirements of these laws could adversely affect our financial condition.

Our operations abroad may also be subject to increased scrutiny or attention from data protection authorities. For example, in Europe, we are subject to the European Union General Data Protection Regulation, (EU GDPR) wentand intoto effectthe inUnited MayKingdom General Data Protection Regulation and Data Protection Act 2018 and imposes strict requirements for processing(collectively, the personalUK dataGDPR) of(the individualsEU withinGDPR and UK GDPR together referred to as the European Economic Area (EEAGDPR). Companies that must comply with the GDPR face increased compliance obligations and risk, including more robust regulatory enforcement of data protection requirements and potential fines for noncompliance of up to €20 million / £17.5 million or 4% of the annual global revenues of the noncompliant company, whichever is greater. Among other requirements, the GDPR regulates transfers of personal data subject to the GDPR to third countries that have not been found to provide adequate protection to such personal data, including the United States, and the efficacy and longevity of current transfer mechanisms between the EEA, and the United States remains uncertain. Case law from the Court of Justice of the European Union (CJEU) states that reliance on the standard contractual clauses - a standard form of contract approved by the European Commission as an adequate personal data transfer mechanism alone may not necessarily be sufficient in all circumstances and that transfers must be assessed on a case-by-case basis. On July 10, 2023, the European Commission adopted its Adequacy Decision in relation to the new EU-US Data Privacy Framework (DPF), rendering the DPF effective as a GDPR transfer mechanism to U.S. entities self-certified under the DPF. We expect the existing legal complexity and uncertainty regarding international personal data transfers to continue. In particular, we expect the DPF Adequacy Decision to be challengedcontinue, and international transfers to the United States and to other jurisdictions more generally to continue to be subject to enhanced scrutiny by regulators. As athe result,regulatory we may have to make certain operational changesguidance and weenforcement willlandscape havein relation to implement revised standard contractual clauses and other relevant documentation for existing data transfers withincontinue requiredto time frames. As supervisory authorities issue further guidance on personal data export mechanisms, including circumstances where the SCCs cannot be used, and/or start taking enforcement action,develop, we could suffer additional costs, complaints and/or regulatory investigations or fines, and/or if we are otherwise unable to transfer personal data between and among countries and regions in which we operate, it could affect the manner in which we provide our services, the geographical location or segregation of our relevant systems and operations, and could adversely affect our financial results.

For example, in March 2010, the Patient Protection and Affordable Care Act,Act as amended by the Health Care and Education Reconciliation Act, collectively, the ACA,(ACA) was enacted in the United States.States in 2010. Among the provisions of the ACA of importance to our potential product candidates, the ACA: established an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents; extended manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations; expanded eligibility criteria for Medicaid programs; expanded the entities eligible for discounts under the 340B drug pricing program; increased the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program; created a new Medicare Part D coverage gap discount program, which was replaced by a new manufacturer discount program on January 1, 2025 (as discussed below); established a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in and conduct comparative clinical effectiveness research, along with funding for such research; and established a Center for Medicare and Medicaid Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending. Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

In addition, other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. On August 2, 2011, theThe Budget Control Act of 2011 was signed into law, which,2011, among other things, resulted in reductions toreduced Medicare payments to providers, which went into effect on April 1, 2013 and, due to subsequent legislative amendments to the statute,and will remain in effect intountil 2032, with the exception of a temporary suspension from May 1, 2020 through March 31, 2022, unless additional Congressional action is taken. On January 2, 2013, theThe American Taxpayer Relief Act of 2012 was signed into law, which,2012, among other things, reduced Medicare payments to several providers, including hospitals, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. In March 2021, Congress enacted the American Rescue Plan Act of 2021, which, among other things, eliminated the statutory cap on drug manufacturers’ Medicaid Drug Rebate Program rebate liability, effective January 1, 2024. Drug manufacturers’ Medicaid Drug Rebate Program rebate liability was previously capped at 100% of the average manufacturer price for a covered outpatient drug.

In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations, which have tended tomay become more stringent over time. These current or future laws and regulations may impair our research, development or production efforts. Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions or liabilities, which could materially adversely affect our business, financial condition, results of operations and prospects.

In the ordinary course of business, we collect, store, transmit and otherwise process large amounts of confidential information including, without limitation, intellectual property, proprietary business information, preclinical and clinical trial data, health-related information and personal information (collectively, Confidential Information). We face evolving cybersecurity risks that threaten the confidentiality, integrity and availability of our information technology systems and Confidential Information. Despite the implementation of security measures, our information technology systems (including infrastructure) and those of our current and any future CROs and other contractors, consultants and collaborators are vulnerable to attack, damage or interruption from diverse threat actors, such as state-sponsored organizations, opportunistic hackers and hacktivists, as well as through diverse attack vectors, including computer viruses and malware (e.g. ransomware), malicious code, cybersecurity threats (such as denial-of-service attacks, cyberattacks or cyber-intrusions over the Internet, hacking, phishing and other social engineering attacks),attacks, misconfigurations, “bugs” or other vulnerabilities, fraud, sophisticated nation-state and nation-state-supported actors, unauthorized access or use, natural disasters, terrorism, war, and telecommunication and electrical failures. Our systems are also subject to compromise from internal threats, such as theft, misuse, unauthorized access or other improper or accidental actions by employees, vendors and other third parties with otherwise legitimate access to our systems. Third parties may also attempt to fraudulently induce our employees and contractors into disclosing sensitive information such as usernames, passwords or other information, or otherwise compromise the security of our electronic systems, networks, and/ or physical facilities in order to gain access to our data.

Cyberattacks are expected to accelerate on a global basis in frequency and magnitude as threat actors are becoming increasingly sophisticated in using techniques and tools – including artificial intelligence – that circumvent security controls, evade detection and remove forensic evidence. As a result, we may be unable to detect, investigate, remediate or recover from future attacks or incidents, or to avoid a material adverse impact to our information technology systems, Confidential Information or business. Given the unpredictability of the timing, nature and scope of information technology disruptions, there can be no assurance that any security procedures and controls that weour or our third-party partnerspartners’ and service providersproviders’ havecybersecurity implementedrisk management programs and processes, including any related policies, controls or procedures, will be sufficientfully toimplemented, preventcomplied cyberattackswith fromor occurring.effective in protecting our information technology systems and Confidential Information. The latency of a compromisecyberattack is often measured in months, but could be years, and we may not be able to detect such a compromise in a timely manner. New techniques may not be identified until they are launched against a target, and we may be unable to anticipate these techniques or detect an incident, assess its severity or impact, react or appropriately respond in a timely manner or implement adequate preventative measures, resulting in potential data loss or other damage to our information technology systems.

We and certain of our service providers are from time to time subject to cyberattacks and security incidents. While we do not believe that we have experienced any significant system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our or our third party service provider’s operations or result in the unauthorized disclosure of or access to Confidential Information (violating certain privacy laws such as the GDPR), it could result in a material disruption of our development programs and our business operations, whether due to a loss of our trade secrets or other similar disruptions. Some of the federal, state and foreign government requirements include obligations of companies to notify individuals, governmental authorities, supervisory bodies, the media and other parties of security breaches involving particular personally identifiable information, which could result from breaches experienced by us or by our vendors, contractors, or organizations with which we have formed strategic relationships. Also, due to the continued hybrid working environment, many of our employees are working remotely. As a result, we may have increased cyber security and data security risks, due to increased use of home wi-fi networks and virtual private networks, as well as increased disbursement of physical machines. While we implement information technology controls to reduce the risk of a cyber security or data security breach, there is no guarantee that these measures will be adequate to safeguard all systems, especially with an increased number of employees working remotely. Furthermore, any integration of artificial intelligence in our or any third party’s operations, products or services is expected to pose new or unknown cybersecurity risks and challenges.

Any security breach or other incident, whether real or perceived, could impact our reputation, impact the availability, integrity or confidentiality of our data, causeresult us to incur significant costs, includingin legal expenses,claims or proceedings (such as class actions), harm customer confidence, hurt our expansion into new markets, cause us to incur remediation costs,costs or cause us to lose existing customers. For example, the loss of clinical trial data from clinical trials could result in delays in our marketing approval efforts and significantly increase our costs to recover or reproduce the data. We also rely on third parties to manufacture our product candidates, and similar events relating to their computer systems could also have a material adverse effect on our business. To the extent that any real or perceived disruption or security breach affects our systems (or those of our third-party collaborators, service providers, contractors or consultants) or were to result in a loss of or accidental, unlawful or unauthorized access to, use of, release of, or other processing of Confidential Information, or damage to, our data or applications, or inappropriate disclosure of Confidential Information, we could incur liability, the further development and commercialization of our product candidates could be delayed, and we could be subject to significant incident response, system restoration or remediation and future compliance costs, as well as significant fines, penalties or liabilities for any noncompliance to certain privacy and security laws. We maintain cyber liability insurance; however, this insurance may not be sufficient to cover the financial, legal, business or reputational losses that may result from an interruption or breach of our systems.

Moreover, the claim coverage in a patent application can be significantly reduced before the patent is granted. Even if they issue, our pending patent applications may not issue in a form that will provide us with any meaningful protection, prevent competitors or other third parties from competing with us or otherwise provide us with any competitive advantage, and patents issuing from our patent applications may be challenged, narrowed, circumvented or invalidated by third parties. Consequently, we do not know whether our product candidates and other proprietary technology will be protectable or remain protected by valid and enforceable patents. Our competitors or other third parties may be able to circumvent our existing patent or patents issuing from our patent applications by developing similar or alternative technologies or products in a non-infringing manner which could materially adversely affect our business, financial condition, results of operations and prospects. In addition, given the amount of time required for the development, testing and regulatory review of our product candidates, patents protecting the product candidates might expire before or shortly after such product candidates are commercialized. As a result, our intellectual property may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

Filing, prosecuting and defending patents on our product candidates and other proprietary technologies we may develop in all countries throughout the world would be prohibitively expensive, and the laws of foreign countries may not protect our rights to the same extent as the laws of the United States. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and, further, may export otherwise infringing products to territories where we have patent protection but enforcement is not as strong as that in the United States. These products may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

Finally,In addition, a Unitary Patent and Unified Patent Court (UPC) system was implemented in Europe on June 1, 2023.2023, which has become a common forum for challenging patents in the pharmaceutical space. This new regime may present uncertainties for our ability to protect and enforce our patent rights against competitors in Europe. Under the UPC, all European patents, including those issued prior to ratification of the European Patent Package, will automatically fall under the jurisdiction of the UPC. The UPC provides our competitors with a new forum to centrally revoke our European patents, and allows for the possibility of a competitor to obtain pan-European injunctions. It will be several years before we will understand the scope of patent rights that will be recognized and the strength of patent remedies that will be provided by the UPC. Under the EU Patent Package, we will have the right to opt our patents out of the UPC over the first seven years of the court’s existence, but doing so may preclude us from realizing the benefits of the new unified court.

Periodic maintenance fees, renewal fees, annuity fees, and various other government fees on patents and applications will be due to be paid to the USPTO and various government patent agencies outside of the United States over the lifetime of our patents and applications. The USPTO and various non-U.S. government agencies require compliance with several procedural, documentary, fee payment and other similar provisions during the patent application process. In some cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with the applicable rules. There are situations, however, in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in a partial or complete loss of patent rights in the relevant jurisdiction. In such an event, potential competitors might be able to enter the market with similar or identical products or technology, which could have a material adverse effect on our business, financial condition, results of operations, and prospects. In addition, there could be delays at the USPTO caused by staffing cuts and other U.S. government actions as a result of the U.S. Department of Government Efficiency or other executive actions to reduce the size of the U.S. government.

Changes in either the patent laws or interpretation of the patent laws in the United States could increase the uncertainties and costs surrounding the prosecution of patent applications and the enforcement or defense of issued patents. Since March 2013, under the Leahy-Smith America Invents Act (the America Invents Act) enacted in September 2011, the United States transitioned to a first inventor to file system in which, assuming that other requirements for patentability are met, the first inventor to file a patent application will be entitled to the patent on an invention regardless of whether a third party was the first to invent the claimed invention. A third party that files a patent application in the USPTO after March 2013, but before us could therefore be awarded a patent covering an invention of ours even if we had made the invention before it was made by such third party. This will require us to be cognizant going forward of the time from invention to filing of a patent application. Since patent applications in the United States and most other countries are confidential for a period of time after filing or until issuance, we cannot be certain that we were the first to either (i) file any patent application related to our product candidates and other proprietary technologies we may develop or (ii) invent any of the inventions claimed in our patent applications. There remains many subsisting issued patents and some pending patent applications in the U.S. that were filed prior to enactment of the America Invents Act, and are therefore subject to the pre-America Invents Act U.S. patent laws, which may have relevance to our freedom-to-operate or ability to obtain patent issuances.

Numerous U.S. and foreign issued patents and pending patent applications owned by third parties exist in the fields in which we are commercializing or plan to commercialize our product candidates and in which we are developing other proprietary technologies. As the biopharmaceutical and biotechnology industries expand and more patents are issued, the risk increases that our product candidates and commercializing activities may give rise to claims of infringement of the patent rights of others. We cannot assure you that our product candidates and other proprietary technologies we may develop will not infringe existing or future patents owned by third parties. We may not be aware of patents that have already been issued and that a third party, for example, a competitor in the fields in which we are developing our product candidates, might assert as infringed by us. It is also possible that patents owned by third parties of which we are aware, but which we do not believe we infringe or that we believe we have valid defenses to any claims of patent infringement, could be found to be infringed by us. It is not unusual that corresponding patents issued in different countries have different scopes of coverage, such that in one country a third-party patent does not pose a material risk, but in another country, the corresponding third-party patent may pose a material risk to our planned products. As such, patents owned by third parties of which we monitorare third-partyaware patentsare monitored in the relevant pharmaceutical markets. In addition, because patent applications can take many years to issue and may be confidential for 18 months or more after filing, there may be currently pending patent applications that may later result in issued patents that we may infringe.

We are a clinical-stage biotechnology company focused on developing next-generation precision medicines for large opportunities in targeted oncology and genetically defined conditions, withharnessing anthe initialpower focus onof Fibroblast Growth Factor Receptor (FGFR) biology.

Our in-house precision medicine platform, SNÅP, enables rapid and precise drug design through iterative molecular SNÅPshots that help us design and predict which product candidates may demonstrate the highest potency, selectivity and tolerability in the clinic. WeThrough this approach, we have initiallybuilt leverageda ourwholly-owned SNÅPpipeline approachof to develop TYRA-300, TYRA-200 and TYRA-430: three clinical-stage, noveloral small moleculesmolecule designedproduct tocandidates overcomefocused theon toxicitytargets andthat resistancehave liabilitiespreviously ofbeen firstconsidered generation pan-FGFR inhibitors.difficult-to-drug.

Our FGFR3 Programs—oral -dabogratinib (formerly TYRA-300) for BladderUrothelial CancerCancers and Skeletal ConditionsDysplasia

MutationsAlterations in the protein receptor FGFR3 are a keyvalidated driver in twomultiple indications with large market opportunities: bladderurothelial cancercancers and skeletal dysplasia conditions. In bladderurothelial cancer, uncontrolled activation of FGFR3 on the cell surface stimulates cellular proliferation. In skeletal dysplasia conditions, increased activity of FGFR3 expressed in growth plate chondrocytes (cartilage cells) results in excessive limitation of long bone growth.

Our lead program, TYRA-300,oral dabogratinib, was designed to be more selective for FGFR3 over FGFR1, FGFR2, and FGFR4 to minimize off-target side effects, providing potential clinical advantages over less selective first-generation compounds and potentially addressing key unmet needs across both bladderurothelial cancercancers and skeletal dysplasia conditions. To date, oral dabogratinib has been administered to over 100 participants across multiple clinical studies.

TYRA-300We isare tocurrently beadvancing evaluatedoral dabogratinib in three Phase 2 studiestrials for three outsized market indications: SURF301,SURF303, forevaluating the treatment of metastaticlow-grade upper tract urothelial carcinoma (mUCLG-UTUC); SURF302, forevaluating the treatment of intermediate risk non-muscle invasive bladder cancer (IR NMIBC); and BEACH301, forevaluating the treatment of pediatric achondroplasia (ACH). in children. If we are successful with these Phase 2 studies, we expect to advance oral dabogratinib toward three potential registrational trials in LG-UTUC, IR NMIBC and ACH. We are calling this approach our “dabogratinib 3x3” strategy.

SURF302SURF303 for NMIBCLG-UTUC: This study is an open-label Phase 22a/b clinical trial evaluatingwas designed as a potential registrational trial to evaluate the efficacy and safety of TYRA-300oral dabogratinib at lower doses (50of 60 mg and 60mg80 mg once daily (QD) in participants with FGFR3-altered low-grade,low-grade intermediateupper risktract (IR)urothelial NMIBC.carcinoma, Wewhere expectapproximately to85% doseof tumors are driven by FGFR3. Study startup is ongoing and the first patient in this study is anticipated to be dosed in the second quarter of 2025.2026.

BEACH301 for ACH: This study is an open-label, Phase 2 dose-escalation/dose-expansion trial evaluating TYRA-300oral dabogratinib at lower doses (0.125, 0.25, 0.375, 0.50 mg/kg), as compared to the oncology studies, in children ages 3 to 10 with ACH with open growth plates.plates, Priorwhere toapproximately initiation99% of thecases firstare twodriven cohorts,by theFGFR3. The study willis enrollenrolling a safety sentinel cohort of up to 3 treatment-naïveor more participants per dose level in children ages 5 to 10.10, Weand expecta natural history run-in for cohorts 1 and 2 with children ages 3 to dose10. Initial results from the firstsafety childsentinel incohort, thisincluding study6-month average height velocity (AHV) results and interim safety, are on-track and expected to be reported in the second quarterhalf of 2025.2026.

TYRA-430 was designed to be biased for FGFR4 and FGFR3 over the FGFR1 and FGFR2 isoforms specifically to address the FGF19 signaling pathway, while also potentially limiting side effects due to inhibition of FGFR1 and FGFR2, as well as to address acquired resistance mutations that have limited the efficacy of previous FGFR4-specific inhibitors. TYRA-430 willis becurrently initiallybeing studiedevaluated in SURF431, a globalglobal, Phase 11, multicenter, open-label,open-label studytrial, with a focus on achieving clinical proof-of-concept in advanceda HCCcohort andof other solid tumorspatients with activatingFGF19+ FGF/FGFRhepatocellular pathway aberrationscarcinoma (SURF431HCC). We expect to dose the first patient in this study in the second quarter of 2025.

Since the commencement of our operations in 2018, we have devoted substantially all of our resources to organizing and staffing the company, business planning, raising capital, developing our proprietary SNÅP platform, undertaking research and development activities for our development programs, establishing our intellectual property portfolio, and providing general and administrative support for our operations. We have not generated any revenue to date and have funded our operations primarily from our initial public offering (IPO), private placements of our convertible preferred stock, the issuance of Simple Agreements for Future Equitystock and the issuance of common stock and pre-funded common stock warrants through a private placement. Our net losses for the years ended December 31, 20242025 and 20232024 were $86.5$119.9 million and $69.1$86.5 million, respectively. As of December 31, 2024,2025, we had an accumulated deficit of $251.3$371.3 million. As of December 31, 2024,2025, we had cash, cash equivalents, and marketable securities of $341.4$256.0 million.

We have incurred significant operating losses since inception. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our clinical development activities, other research and development activities and capital expenditures. We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future particularly if and as we conductcontinue preclinicalto studiesdevelop and conduct clinical trials,trials for our product candidates, continue our research and development activities,activities utilizefor thirdfuture partiesproduct tocandidates, manufactureexpand our product candidatesclinical and relatedregulatory rawcapabilities, materials,add operational and management information systems and hire additional personnel, expand and protect our intellectual property, establish marketing, sales, distribution and other commercialization capabilities if we obtain approval for any of our product candidates and incur additional costs associated with beingoperating as a public company.

employee-related expenses, including salaries, related benefits, recruiting costs, travel and share-based compensation expenses for employees engaged in research and development functions;

We expense research and development expenses in the periods in which they are incurred. External expenses are recognized based on an evaluation of the progress to completion of specific tasks using information provided to us by our service providers or our estimate of the level of service that has been performed at each reporting date. We track external expenses on a development program and other program-specific basis. However, we do not track internal costs, such as personnel-related expenses, stock-based compensation expense, facility-related costs and supplies and certain external consultant costs on a program-specific basis because these costs primarily relate to compensation, early research and consumable costs, which are deployed across multiple programs under development.

Research and development activities are central to our business model. There are numerous factors associated with the successful development of any of our product candidates, including future trial design and various regulatory requirements, many of which cannot be determined with accuracy at this time based on our stage of development. In addition, future regulatory factors beyond our control may impact our clinical development programs. Product candidates in later stages of development generally have higher development costs than those in earlier stages of development. As a result, we expect that our research and development expenses will increase substantially over the next several years as we advance our product candidates into later phases of clinical trials or through preclinical studies into and through clinical trials, continue to discover and develop additional product candidates and expand our pipeline, maintain, expand, protect and enforce our intellectual property portfolio,portfolio and hire additional personnel.

geopolitical instability, such as theincluding war and other conflicts in Ukraine and the Middle Eastterrorism;

adverse effects on the financial markets, the global economy, the supply chain and our expenses due to tariffs and trade policies, pandemic or epidemic diseases, geopolitical instability, inflation, interest rates and other factors; and the extent to which we establish additional strategic collaborations or other arrangements.

Other income consistconsists primarily of interest income from cash, cash equivalents and marketable securities and accretion income from marketable securities.

Research and development expenses were $80.1$102.9 million and $62.5$80.1 million for the years ended December 31, 20242025 and 2023,2024, respectively. The overall increase of $17.6$22.8 million was primarily driven by:

General and administrative expenses were $24.1$29.8 million and $17.4$24.1 million for the years ended December 31, 20242025 and 2023,2024, respectively. The increase of $6.7$5.7 million was primarily related to higher compensation and other personnel expenses, including an increase in non-cash stock-based compensation costs of $3.7 million, driven by: headcount growth.

Other income was $17.7$12.8 million and $10.8$17.7 million for the years ended December 31, 20242025 and 2023,2024, respectively. The increasedecrease of $6.9$4.9 million was primarily relateddue to anlower increaseinterest rates and reduced balances in our cash, cash equivalents and marketable securities balances due to proceeds received from our private placement completed in February 2024.securities.

On October 3, 2022, we entered into an ATM Sales Agreement (the 2022 Sales Agreement) with Virtu Americas LLC (the 2022 Sales Agent), under which we may,could have, from time to time, sellsold shares of our common stock having an aggregate offering price of up to $150.0 million in “at the market” offerings through the Agent.2022 Sales of the shares of common stock, if any, will be made at prevailing market prices at the time of sale or as otherwise agreed with the Agent. TheWe Agent will receive a commission from us of up to 3.0% of the gross proceeds of any shares of common stock sold under the Sales Agreement. As of December 31, 2024, we havedid not soldsell any shares under the 2022 Sales Agreement. In connection with the 2025 Sales Agreement (as defined below), effective May 8, 2025, we terminated the 2022 Sales Agreement.

NetThe increase of $170.9 million in net cash usedprovided inby investing activities for the year ended December 31, 20242025, compared to the same period in 2024, was $98.4driven million,by consistinga ofreduction $263.6 million forin purchases of marketable securities available-for-saleof and$162.4 $0.7million, a $8.0 million forincrease purchases of property and equipment, offset by $165.9 forin maturities of marketable securitiessecurities, available-for-sale.and a $0.5 million decrease in capital expenditures for property and equipment.

NetThe decrease of $194.0 million in net cash provided by financing activities for the year ended December 31, 20242025, compared to the same period in 2024, was $202.1 million, consisting primarily ofdue proceeds fromto the issuance$199.6 ofmillion commonin stocknet and pre-funded warrantsproceeds from the 2024 Private Placement ofreceived $200during million,the year ended December 31, 2024. This decrease was partially offset by issuancean costsincrease of $0.4$5.6 million,million andin proceeds from the issuanceissuances of common stock under benefit plans of $2.5 million.plans.

Our material cash requirements consist of expected operating expenses to conduct our clinical trials and other research and development activities, facilitypersonnel-related expenses and operating lease obligations.

Our primary uses of cash to date have been to fund our research and development activities, including with respect to TYRA-300,dabogratinib, TYRA-300 ACH, TYRA-430 andTYRA-430, TYRA-200 and other research programs, business planning, establishing and maintaining our intellectual property portfolio, hiring personnel, raising capital, and providing general and administrative support for these operations.

costs associated with any products or technologies that we may in-license or acquire; and delays or issues with any of the above, including that the risk of each may be exacerbated by tariffs or trade policies, any future pandemics or epidemic diseases, potential geopolitical instability andinstability, war, terrorism, inflation or rising interest rates.

The Company has entered into various research and development contracts with clinical research organizations, clinical manufacturing organizations, clinical sites and other vendors and consultants. Payments for these activities are based on the terms of the individual agreements, which may differ from the pattern of costs incurred, and payments made in advance of or after the performance are reflected in the accompanying balance sheets as prepaid expenses or accrued liabilities, respectively. The Company records accruals for estimated costs incurred for ongoing research and development activities. When evaluating the adequacy of the accrued liabilities, the Company analyzes the progress of the services, including the phase or completion of events, invoices received and contracted costs. The Company holds discussions with applicable personnel and outside service providers as to the progress of clinical trials, or the services completed. Significant judgments and estimates may be made in determining the prepaidstatus orand accrued balances at the endtiming of anyservices reportingperformed, period.and Actualactual results could differ from the Company’s estimates. Nonrefundable advance payments for goods and services, including fees for process development, are deferred and recognized as expenses in the period that the related goods are consumed or services are performed.

Our lead program, oral dabogratinib, was designed to be more selective for FGFR3 over FGFR1, FGFR2, and FGFR4 to minimize off-target side effects, providing potential clinical advantages over less selective first-generation compounds and potentially addressing key unmet needs across both urothelial cancers and skeletal dysplasia conditions. To date, oral dabogratinib has been administered to over 100200 participantsindividuals across multiple clinical and healthy volunteer studies.

SURF303 for LG-UTUC: This open-label Phase 2a/b clinical trial was designed as a potential registrational trial to evaluate the efficacy and safety of oral dabogratinib at doses of 60 mg and 80 mg once daily (QD) in participants with FGFR3-altered low-grade upper tract urothelial carcinoma,LG-UTUC, where approximately 85% of tumors are driven by FGFR3. The Company hasis dosedcurrently thedosing firstand patientenrolling patients in SURF303, with initial results expected in 2027.

SURF302 for IR NMIBC: This open-label Phase 2 clinical trial is evaluating the efficacy and safety of oral dabogratinib at 50 mg and 60 mg QD in participants with FGFR3-altered low-grade IR NMIBC, where approximately 70% of tumors are driven by FGFR3. To date, there are more than 20 patients enrolled at US and international trial sites, and theThe Company expects to report initial three-month complete response dataresults from both dose cohorts during a conference call and webcast in AugustSeptember 2026.2026, including safety results from more than 40 patients and efficacy from more than 20 patients in the aggregate at both QD dose levels.

BEACH301 for ACH: This study is an open-label, Phase 2 dose-escalation/dose-expansion trial evaluating oral dabogratinib at lowermultiple doses (0.125, 0.25, 0.375, 0.500.50, and 0.625 mg/kg), as compared to the oncology studies, in children ages 3 to 10 with ACH with open growth plates, where approximately 99% of cases are driven by FGFR3. The study has enrolled the safety sentinel cohort, consisting of at least 3 participants per dose level in children ages 5 to 10, and is enrolling a natural history run-in for cohorts 1 and 2 with children ages 3 to 10. No notable safety events have been reported to date. Initial results from the safety sentinel cohort, including 6-month averageannualized height velocity and safety data,data from all five dose levels, are on-track and expected to be reported inat the fourthend of the first quarter of 2026.2027, which will include an aggregate of approximately 25 children.

Since the commencement of our operations in 2018, we have devoted substantially all of our resources to organizing and staffing the company, business planning, raising capital, developing our proprietary SNÅP platform, undertaking research and development activities for our development programs, establishing our intellectual property portfolio, and providing general and administrative support for our operations. We have not generated any revenue to date and have funded our operations primarily from our initial public offering (IPO), private placements of our convertible preferred stock, the issuance of common stock and pre-funded common stock warrants through a private placement and the issuance of common stock through an at-the-market offering program. Our net losses for the threesix months ended MarchJune 31,30, 2026 and 2025 were $39.3$84.9 million and $28.1$56.2 million, respectively. As of MarchJune 31,30, 2026, we had an accumulated deficit of $410.6$456.1 million. As of MarchJune 31,30, 2026, we had cash, cash equivalents and marketable securities of $383.5$353.9 million.

Based on our current operating plan, we believe that our cash, cash equivalents and marketable securities as of MarchJune 31,30, 2026 will be sufficient to fund our operating expenses and capital expenditures into the second half of 2028. We have never generated any revenue and do not expect to generate any revenue from product sales unless and until we successfully complete the development of and obtain regulatory approval for our product candidates, which will not be for several years, if ever. In addition, if we obtain regulatory approval for any of our product candidates, we expect to incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution. Accordingly, until we can generate significant revenue from sales of our product candidates, if ever, we expect to finance our cash needs through equity offerings, debt financings or other capital sources, including potential collaborations, licenses and other similar arrangements. However, we may not be able to raise additional funds or enter into such other arrangements when needed or on favorable terms, or at all. If we are unable to raise additional capital or enter into such arrangements when needed, we could be forced to delay, limit, reduce or terminate our research and development programs or future commercialization efforts, or grant rights to develop and market our product candidates even if we would otherwise prefer to develop and market such product candidates ourselves.

Comparison of the Three Months Ended MarchJune 31,30, 2026 and 2025

Research and development expenses were $33.5$39.2 million and $25.0$24.3 million for the three months ended MarchJune 31,30, 2026 and 2025, respectively. The $8.5$14.9 million increase was primarily driven by a $4.5$7.8 million increase in external costs, including aan $5.5$8.7 million increase related to dabogratinib development activities supporting the ongoing BEACH301SURF303, SURF302 and SURF302BEACH301 clinical trials and start-up activities for SURF303,trials, partially offset by a $1.0$0.9 million decrease in development activities for other programs. Personnel-relatedThe expensesremaining alsoincrease increased by $3.8 million,was driven by a $6.5 million increase in personnel-related expenses primarily due to headcount growth to support expanding clinical and development activities.activities and a $0.5 million increase in facilities and other costs.

General and administrative expenses were $8.5$9.8 million and $6.9$7.1 million for the three months ended MarchJune 31,30, 2026 and 2025, respectively. The increase of $1.6$2.7 million was primarily related to higher compensation and other personnel expenses, including an increase in non-cash stock-based compensation costs of $0.6$1.8 million, driven by headcount growth.

Other income was $2.7$3.5 million and $3.7$3.4 million for the three months ended MarchJune 31,30, 2026 and 2025, respectively. The decreaseincrease of $1.0$0.1 million was driven by lower interest rates and reducedhigher average balances inof cash, cash equivalents and marketable securities prior tofollowing the receipt of proceeds underfrom the at-the-market offering program.

On May 8, 2025, we entered into a sales agreement (the 2025 Sales Agreement) with TD Securities (USA) LLC (Sales Agent), under which we may,could, from time to time, sell shares of our common stock having an aggregate offering price of up to $150.0 million in at-the-market offerings through the Sales Agent. Sales ofDuring the sharesthree ofmonths common stock, if any, will be made at prevailing market prices at the time of sale or as otherwise agreed with the Sales Agent, in accordance with the terms of the 2025 Sales Agreement. As ofended March 31, 2026, 4,690,532 shares of common stock have beenwere issued and sold pursuant to the 2025 Sales Agreement for net proceeds of approximately $147.9 million, after deducting offering expenses.expenses, fully utilizing the capacity under the 2025 Sales Agreement.

The increase of $7.1$14.5 million in net cash used in operating activities for the threesix months ended MarchJune 31,30, 2026, compared to the same period in 2025, was primarily due to an increase of $11.2$28.6 million in net loss, offset by changes in operating assets and liabilities of $1.9$7.5 million, increases of $1.4$5.3 million in non-cash stock-based compensation expense and $0.8$1.3 million in non-cash net accretion on marketable securities.

The changeincrease of $152.3$155.3 million in net cash used in investing activities for the threesix months ended MarchJune 31,30, 2026, compared to net cash provided by investing activities for the same period in 2025, was primarily drivendue byto an increase of $157.3 million in purchases of marketable securities of $155.3 million and a $0.1 million increase in purchases of property and equipment, partially offset by a $3.1$2.1 million increase in maturities of marketable securities.

The increase of $158.2$159.7 million in net cash provided by financing activities for the threesix months ended MarchJune 31,30, 2026, compared to the same period in 2025, was primarily due to the $147.9 million in net proceeds from the sale of common stock under the 2025 Sales Agreement and an increase of $10.3$11.8 million in proceeds from issuances of common stock under benefit plans.

Based on our current operating plan, we believe that our existing cash, cash equivalents and marketable securities as of MarchJune 31,30, 2026 will be sufficient to meet our anticipated operating expenses and capital expenditures into the second half of 2028. However, our forecast of the period of time through which our financial resources will be adequate to support our operations is a forward-looking statement that involves risks and uncertainties, and actual results could vary materially. We have based this estimate on assumptions that may prove to be wrong, and we could deplete our capital resources sooner than we expect. Additionally, the process of conducting preclinical studies and testing product candidates in clinical trials is costly, and the timing of progress and expenses in these studies and trials is uncertain.

Other than disclosed below, there were no material changes outside the ordinary course of our business during the threesix months ended MarchJune 31,30, 2026 to the information regarding our contractual obligations that was disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in the 2025 Annual Report.

As of MarchJune 31,30, 2026, total future aggregate operating lease commitments were $7.6$7.4 million, with approximately $0.7$0.5 million due during 2026, and the remaining due in periods from 2027 through 2033.

There have been no material changes to our critical accounting policies and estimates during the threesix months ended MarchJune 31,30, 2026, as compared to the critical accounting policies and estimates disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in the 2025 Annual Report.