Vaxcyte (5VA) Risk Analysis

We are developing a pipeline of vaccine candidates utilizing our cell-free protein synthesis platform, which is comprised of the XpressCF platform exclusively licensed from Sutro Biopharma, Inc. ("Sutro Biopharma") and our proprietary know-how for vaccine applications against infectious disease. Our future success depends on the successful application of this approach to vaccine development. We are in the clinical or preclinical stages of developing our vaccine candidates and there can be no assurance that any development problems we may experience in the future will not cause significant delays or unanticipated costs, or that such development problems can be overcome. For example, although we have achieved proof-of-concept for our carrier-sparing approach with VAX-31 and VAX-24, our approach may not be validated for our other vaccine candidates or subsequent trials of VAX-31 or VAX-24. We may also experience delays in developing a sustainable, reproducible and scalable manufacturing process or transferring that process to manufacturing partners, which may prevent us from completing our clinical trials or commercializing our products on a timely or profitable basis, if at all. In addition, since we have not yet completed clinical development on any of our product candidates, we do not know the specific doses that may be effective in the clinic or, if approved, commercially. Finding a suitable dose may delay our anticipated clinical development timelines. We may also encounter difficulty recruiting sufficient participants for our clinical studies, or the FDA may impose additional requirements on us regarding trial size or a long-term safety study that will significantly slow or forestall our development program. Furthermore, our expectations with regard to our scalability and costs of manufacturing may vary significantly as we develop our vaccine candidates and learn more about these critical factors. Conjugate vaccine development is highly complex, and development of broad-valency pneumococcal conjugate vaccines ("PCVs") is further complicated by the number of components, analytical assays and potential for adjustments, including, but not limited to, changes in raw materials, composition, formulation, manufacturing methods and dosing, which could result in drug substances and/or drug product that may vary between preclinical and clinical studies over time. Over the course of the development and manufacturing of VAX-24, we previously encountered process-related matters that required us to make adjustments to our processes. For example, in 2020 we encountered such process-related matters during our drug substance manufacturing campaign for VAX-24 at Lonza, Ltd. ("Lonza"). The cumulative impact of the time required to make adjustments to our processes led to a delay of our drug substance manufacturing campaign due to scheduling conflicts and capacity constraints at Lonza. There can be no assurance that we or Lonza will be able to successfully manufacture drug substances in a timely manner in the future, or at all. Such process changes and manufacturing delays have caused a change in our Investigational New Drug ("IND") application timelines in the past and future changes or delays could impact future timelines for VAX-31, VAX-24 or for our other product candidates. In addition, if we encounter similar manufacturing issues after product approval, it will require inspection and approval of the new manufacturing site and submission of a Biologics License Application ("BLA") supplement, which may further impede or delay commercialization. In addition, the preclinical and clinical trial requirements of the FDA, European Medicines Agency ("EMA") and other regulatory agencies and the criteria these regulators use to determine the safety and immunogenicity or efficacy of a vaccine candidate are determined according to the type, complexity, novelty and intended use and market of the potential products, taking into consideration the benefits and risks for the intended population who will receive the vaccine, as well as the disease(s) to be prevented. Regulatory agencies also evaluate a sponsor's data to determine whether the manufacturing and facility information assure product quality and consistency. Approvals by the FDA and EMA for existing pneumococcal vaccines, such as Pfizer Inc.'s ("Pfizer") Prevnar 13 ("PCV13") and Prevnar 20 ("PCV20"), and Merck & Co., Inc.'s ("Merck") VAXNEUVANCETM ("PCV15"), Capvaxive ("PCV21") and Pneumovax 23 ("PPSV23"), may not be indicative of what these regulators may require for approval of our vaccine candidates. For example, in the adult population, these existing pneumococcal vaccines were previously approved based on the establishment of non-inferiority of OPA responses relative to the then current standard of care vaccine(s), on a strain-by-strain basis, where non-inferiority was defined as greater than or equal to 0.50 of the lower limit of the two-sided 95% confidence interval of the OPA geometric mean titer ratio. Following discussions with the FDA, the non-inferiority standard in our VAX-31 adult OPUS-1 Phase 3 pivotal, noninferiority trial is set at 0.667. The FDA may challenge our VAX-31 Phase 3 Chemistry, Manufacturing and Controls ("CMC") strategy, which could cause significant delays or unanticipated costs. Additionally, novel aspects of our vaccine candidates and manufacturing processes may create further challenges in obtaining regulatory approval. The regulatory approval process for our novel vaccine candidates can be more complex and consequently more expensive and take longer than for other, better known or extensively studied pharmaceutical or other vaccine candidates. More generally, approvals by any regulatory agency may not be indicative of what any other regulatory agency may require for approval or what such regulatory agencies may require for approval in connection with new vaccine candidates. Moreover, our vaccine candidates may not perform successfully in clinical trials. Evolving regulatory approaches to vaccine approval decisions may present additional hurdles to development that would necessitate a change to our approach to meet regulatory expectations.

Our ability to achieve and sustain profitability depends on obtaining regulatory approvals for and successfully commercializing our vaccine candidates, either alone or with third parties, and we cannot guarantee that we will ever obtain regulatory approval for any of our vaccine candidates. We have limited experience in conducting and managing the clinical trials necessary to obtain regulatory approvals, including approval by the FDA, and we may never be able to obtain marketing approval for any of our product candidates. Before obtaining regulatory approval for the commercial distribution of our vaccine candidates, we must conduct extensive preclinical studies and clinical trials to demonstrate the safety and immunogenicity or efficacy of our vaccine candidates. We may not have the financial resources to continue development of, or to enter into new collaborations for, a vaccine candidate if we experience any issues that delay or prevent regulatory approval of, or our ability to commercialize, vaccine candidates, including: - negative or inconclusive results from our preclinical or clinical trials, leading to a decision or requirement to conduct additional preclinical studies or clinical trials or abandon a program;- product-related adverse effects experienced by volunteers in our clinical trials;- difficulty achieving successful development of our manufacturing processes, including process development and scale-up activities to supply products for preclinical studies, clinical trials and commercial sale, if approved;- timely completion of our preclinical studies and clinical trials, including any field efficacy studies that may be required, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors;- inability of us or any third-party contract manufacturer to scale up manufacturing of our vaccine candidates to supply the needs of preclinical studies, clinical trials and commercial sales, and to manufacture such products in conformity with regulatory requirements;- delays in submitting IND applications or comparable foreign applications or delays or failures in obtaining necessary authorizations from regulators to commence a clinical trial, or suspension or termination of a clinical trial once commenced;- conditions imposed by the FDA or similar foreign authorities regarding the scope or design of our clinical trials, including any requirements to perform field efficacy studies;- challenges by the FDA to our clinical or regulatory strategies;- changes in FDA personnel that alter the FDA's advice with respect to our development strategy;- delays in enrolling subjects in our clinical trials;- inadequate supply or quality of vaccine candidate components or materials or other supplies necessary for conducting clinical trials;- inability to obtain alternative sources of supply for which we have a single source for vaccine candidate components;- the availability of coverage and adequate reimbursement and pricing from third-party payors, including government authorities, pertaining to the vaccine candidate, once approved, and patients' willingness to pay out-of-pocket if third-party payor reimbursement is limited or not available;- greater than anticipated costs of our clinical trials, including CMC activities related to our clinical trials;- harmful side effects or inability of our vaccine candidates to meet immunogenicity or efficacy endpoints;- unfavorable FDA or other regulatory agency inspection and review of one or more of our clinical trial sites or our contract manufacturers' facilities;- failure of our third-party contractors or investigators to comply with regulatory requirements or otherwise meet their obligations in a timely manner, or at all;- delays and changes in regulatory requirements, policy and guidelines, including the imposition of additional regulatory oversight around clinical testing generally or with respect to our technology or vaccine candidates in particular; or - varying interpretations of our data by the FDA and comparable foreign regulatory authorities. In addition, changes to the standard-of-care or the approval standards for new vaccines have, and could again in the future, change the threshold for achievement of non-inferiority using the established surrogate immune endpoints that our PCVs will need to meet in our clinical trials. Our inability to complete development of or commercialize our vaccine candidates, or significant delays in doing so due to one or more of these factors, could have a material and adverse effect on our business, financial condition, results of operations and prospects. Moreover, principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and receive compensation in connection with such services. Under certain circumstances, we may be required to report some of these relationships to the FDA or comparable foreign regulatory authorities. The FDA or comparable foreign regulatory authorities may conclude that a financial relationship between us and a principal investigator has created a conflict of interest or otherwise affected interpretation of the study. The FDA or comparable foreign regulatory authorities may therefore question the integrity of the data generated at the applicable clinical trial site and the utility of the clinical trial itself may be jeopardized. This could result in a delay in approval, or rejection, of our marketing applications by the FDA or comparable foreign regulatory authorities, as the case may be, and may ultimately lead to the denial of marketing approval of one or more of our vaccine candidates.

Our business and future success depends on our ability to successfully develop, obtain regulatory approval of, and then commercialize our PCV candidates, which include VAX-31, our 31-valent clinical PCV candidate in development for both the adult and pediatric populations, VAX-24, our 24-valent clinical PCV candidate in development for the pediatric population, and VAX-XL, our third-generation PCV candidate designed to provide the broadest coverage of any PCV currently in development. Although VAX-31 has produced positive topline results in a Phase 1/2 clinical study in adults, it may not demonstrate the same results in the adult pivotal Phase 3 studies needed to obtain marketing approval from the FDA or comparable foreign regulatory authorities or in infant clinical studies. VAX-31 and VAX-24 will require additional clinical and non-clinical development, regulatory review and approval in multiple jurisdictions, substantial investment, access to sufficient clinical and commercial manufacturing capacity and significant marketing efforts before we can generate any revenue from product sales. We cannot provide any assurance that we will be able to successfully advance our PCV candidates through the development process. The clinical and commercial success of VAX-31, VAX-24, and future vaccine candidates will depend on a number of factors, including the following: - our ability to raise any additional required capital on acceptable terms, or at all;- our ability to complete IND-enabling studies and successfully submit IND or comparable applications;- the ability of third parties with whom we contract to manufacture adequate clinical study and commercial supplies of our lead vaccine candidates or any future vaccine candidates, remain in good standing with regulatory agencies and develop, validate and maintain commercially viable manufacturing processes that are compliant with current good manufacturing practices ("cGMP") and do so in a timely manner;- timely completion of our preclinical studies and clinical trials, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors;- whether we are required by the FDA or similar foreign regulatory agencies to conduct additional clinical trials, including field efficacy studies, long-term safety studies, or other studies beyond those planned to support the approval and commercialization of our vaccine candidates or any future vaccine candidates;- acceptance of our proposed indications and primary surrogate endpoint assessments for our PCV candidates by the FDA and similar foreign regulatory authorities;- any changes to the required threshold for the achievement of non-inferiority using established surrogate immune endpoints that our PCVs will need to meet in our clinical trials;- our ability to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities the safety and immunogenicity or efficacy and acceptable risk to benefit profile of our PCV candidates and any future vaccine candidates;- the pace and prevalence of serotype replacement following the introduction of our PCV candidates or other vaccines targeting pneumococcal disease;- any vaccine-vaccine interference studies that may be required, particularly with the standard-of-care pediatric vaccine regimen;- the prevalence, duration and severity of potential side effects or other safety issues experienced with our vaccine candidates or future approved products, if any;- the timely receipt of necessary marketing approvals from the FDA or comparable foreign regulatory authorities;- achieving, maintaining and, where applicable, ensuring that our third-party contractors achieve and maintain compliance with our contractual obligations and with all regulatory requirements applicable to our lead vaccine candidates or any future vaccine candidates or approved products, if any;- obtaining and maintaining Advisory Committee on Immunization Practices ("ACIP"), comparable foreign regulatory authority, professional society, or other clinical recommendation of our vaccine candidates and the willingness of physicians, operators of clinics and patients to utilize or adopt any of our future vaccine candidates to prevent or treat age-associated diseases;- our ability to successfully develop a commercial strategy and thereafter commercialize our vaccine candidates or any future vaccine candidates in the United States and internationally, if approved for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others;- the convenience of our treatment or dosing regimen;- acceptance by physicians, payors and patients of the benefits, safety and immunogenicity or efficacy of our vaccine candidates or any future vaccine candidates, if approved, including relative to alternative and competing treatments;- patient demand for our vaccine candidates, if approved;- our ability to establish and enforce intellectual property rights in and to our vaccine candidates or any future vaccine candidates;- our ability to avoid third-party patent interference, intellectual property challenges or intellectual property infringement claims;- our ability to set an acceptable price for our product candidates and obtain coverage and adequate reimbursement from third-party payors; and - macroeconomic factors that may exacerbate the magnitude of the factors discussed above. These factors, many of which are beyond our control, could cause us to experience significant delays or an inability to obtain regulatory approvals or commercialize our vaccine candidates. Even if regulatory approvals are obtained, we may never be able to successfully commercialize any of our vaccine candidates. Accordingly, we cannot provide assurances that we will be able to generate sufficient revenue through the sale of our vaccine candidates or any future vaccine candidates to continue our business or achieve profitability.

To date, we have devoted substantially all of our resources to performing research and development, undertaking preclinical studies, advancing our vaccine candidates through clinical trials, enabling manufacturing activities in support of our product development efforts, acquiring and developing our technology and vaccine candidates, organizing and staffing our company, performing business planning, establishing our intellectual property portfolio and raising capital to support and expand such activities. As an organization, we have not yet demonstrated an ability to successfully complete clinical development, obtain regulatory approvals, manufacture a commercial-scale product or conduct sales and marketing activities necessary for successful commercialization or arrange for a third party to conduct certain of these activities on our behalf. Consequently, any predictions about our future success or viability may not be as accurate as they could be if we had a longer operating history. We may encounter unforeseen expenses, difficulties, complications, delays, changes in the regulatory environment, and other known or unknown factors in achieving our business objectives, including with respect to our vaccine candidates. We will need to transition at some point from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful in such a transition.

The success of our business depends in large part upon our ability to identify, develop and commercialize products based on our cell-free protein synthesis platform. In addition to our PCV franchise, our pipeline includes preclinical vaccine candidates VAX-A1 for Group A Streptococcus ("Group A Strep") and VAX-GI for dysentery and shigellosis. Our research programs may fail to identify potential vaccine candidates for clinical development for a number of reasons or we may focus our efforts and resources on potential programs or vaccine candidates that ultimately prove to be successful in a smaller subset of patients than expected or completely unsuccessful. In addition, we cannot provide any assurance that we will be able to successfully advance any of our existing or future vaccine candidates through the development process. For example, we announced in August 2025 that preclinical data for VAX-PG demonstrated an acceptable safety profile but not sufficient efficacy signals to support further investment, and we therefore discontinued further development of that candidate. Our potential vaccine candidates may be shown to have harmful side effects, cause allergic reactions, or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval. If any of these events occur, we may be forced to abandon our development efforts for a program or for multiple programs, which would materially harm our business and could potentially cause us to cease operations. Even if we receive FDA approval to market additional vaccine candidates, we cannot provide assurance that any such vaccine candidates will be successfully commercialized, widely accepted in the marketplace or more effective than other commercially available alternatives. In addition, we believe current PCVs do not provide adequate coverage of the strains currently causing pneumococcal disease or those that previously caused pneumococcal disease. There has been a decrease in the incidence of disease attributable to the strains covered by existing vaccines but an increase in incidence attributable to non-covered strains that now cause most residual disease. Such change is driven by the void created when strains are taken out of circulation after widespread vaccination, which is a phenomenon known as serotype replacement. As a result of such change, broader spectrum PCVs are required to maintain protection against historically pathogenic strains while expanding coverage to current circulating and emerging strains. There can be no assurance that we will be able to develop higher-valent vaccines to address serotype replacement. In addition, because VAX-31 and VAX-24 are our most advanced vaccine candidates, and because our other vaccine candidates are also based on our cell-free protein synthesis platform, if VAX-31 or VAX-24 encounter safety or immunogenicity problems, manufacturing problems, developmental delays, regulatory issues or other problems, our development plans and business would be significantly harmed.

Adverse effects or other undesirable or unacceptable side effects caused by our vaccine candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other comparable foreign regulatory authorities. Results of our clinical trials could reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics. In such an event,our clinical trials could be suspended or terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our vaccine candidates. Such side effects could also affect trial recruitment or the ability of enrolled subjects to complete the clinical trial or result in potential product liability claims. An independent data safety monitoring board ("DSMB") may also suspend or terminate a clinical trial at any time on various grounds, including a finding that the research volunteers are being exposed to an unacceptable health risk. Vaccine-related side effects could also affect recruitment or the ability of enrolled subjects to complete the trial or result in potential product liability claims. In addition, any vaccine to be approved in pediatric populations may need to undergo extensive vaccine-vaccine interference studies with the standard-of-care pediatric vaccine regimen. Further, to the extent field efficacy studies are required, prophylactic vaccines typically require clinical testing in thousands to tens of thousands of healthy volunteers to define an approvable benefit-risk profile. The need to show a high degree of safety and tolerability when dosing healthy individuals could result in rare and even spurious safety findings, negatively impacting a program prior to or after commercial launch. Any of these occurrences may harm our business, financial condition and prospects significantly.

Our timing of submitting the IND applications for our product candidates is dependent on preclinical and manufacturing success, and if we experience additional delays, we may fail to meet our anticipated timelines. In addition, we cannot be sure that submission of an IND application or IND application amendment will result in the FDA allowing testing and clinical trials to begin, or that, once begun, issues will not arise that suspend or terminate such clinical trials. Additionally, even if regulatory authorities agree with the design and implementation of the clinical trials set forth in an IND or clinical trial application, we cannot guarantee that such regulatory authorities will not change their requirements in the future.

Clinical testing is expensive, time consuming and subject to uncertainty. We cannot guarantee that any clinical studies will be conducted as planned or completed on schedule, if at all. Even if these trials begin as planned, issues may arise that could suspend or terminate such clinical trials. A failure of one or more clinical studies can occur at any stage of testing, and our future clinical studies may not be successful. Events that may prevent successful or timely completion of clinical development include, but are not limited to: - inability to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the initiation of clinical trials;- delays in sufficiently developing, characterizing or controlling a manufacturing process suitable for advanced clinical trials;- delays in reaching a consensus with regulatory agencies on study design or clinical or regulatory strategies;- delays in reaching agreement on acceptable terms with prospective CROs and clinical study sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical study sites;- delays in obtaining required institutional review board ("IRB") approval at each clinical study site;- imposition of a temporary or permanent clinical hold by regulatory agencies for a number of reasons, including after review of an IND application or amendment, or equivalent application or amendment; as a result of a new safety finding that presents unreasonable risk to clinical trial participants; a negative finding from an inspection of our clinical study operations or study sites; developments on trials conducted by competitors for related technology that raise FDA concerns about risk to patients of the technology broadly; or if the FDA finds that the investigational protocol or plan is clearly deficient to meet its stated objectives;- delays in adding a sufficient number of trial sites and recruiting volunteers to participate in our clinical trials;- failure by our CROs, other third parties or us, to adhere to clinical study requirements;- failure to perform in accordance with the FDA's good clinical practice ("GCP") requirements or applicable regulatory guidelines in other jurisdictions;- transfer of manufacturing processes to any new CMO or our own manufacturing facilities or any other development or commercialization partner for the manufacture of vaccine candidates;- delays in having subjects complete participation in a study or return for post-injection follow-up;- subjects dropping out of a study;- occurrence of side effects associated with our vaccine candidates that are viewed to outweigh their potential benefits;- changes in regulatory requirements and guidance that require amending or submitting new clinical protocols;- changes in the standard-of-care on which a clinical development plan was based, which may require new or additional trials;- the cost of clinical trials of our vaccine candidates being greater than we anticipate;- clinical studies of our vaccine candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical studies or abandon product development programs;- delays or failure to secure supply agreements with suitable raw material suppliers, or any failures by suppliers to meet our quantity or quality requirements for necessary raw materials; and - delays in manufacturing, testing, releasing, validating or importing/exporting sufficient stable quantities of our vaccine candidates for use in clinical studies or the inability to do any of the foregoing. Any inability to successfully complete preclinical and clinical development could result in additional costs to us or impair our ability to generate revenue. In addition, if we make manufacturing or formulation changes to our vaccine candidates, we may be required to or we may elect to conduct additional studies to bridge our modified vaccine candidates to earlier versions. Clinical trial delays could also shorten any periods during which our products have patent protection and may allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our vaccine candidates and may harm our business and results of operations.

We may experience difficulties in enrolling subjects in any clinical trials we may conduct for a variety of reasons. The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of subjects who remain in the study until its conclusion. The enrollment of subjects depends on many factors, including, but not limited to: - the eligibility and exclusion criteria defined in the protocol;- the size of the population required for analysis of the trial's primary endpoints;- the proximity of volunteers to study sites;- the design of the trial;- our ability to recruit clinical trial investigators with the appropriate competencies and experience;- our ability to obtain and maintain subject consents;- the ability to monitor volunteers adequately during and after injection;- the risk that volunteers enrolled in clinical trials will drop out of the trials before the injection of our vaccine candidates or trial completion; and - the risks and disruptions related to patient and physician investigator recruitment and retention and study site initiation and clinical trial activities. Based on our VAX-31 End-of-Phase 2 meeting with the FDA, we believe there is confirmation that the planned immunogenicity analyses are sufficient to support licensure, and an efficacy study is therefore not required. In the event that we are required to conduct any field efficacy studies for VAX-31 or any of our other product candidates, enrollment of a sufficient number of subjects may require additional time and resources given widespread vaccination rates in the United States, particularly in the pediatric population. As a result, we may be required to conduct any such trials outside the United States, which could cause additional complexity and delay. Delays in enrollment may result in increased costs or may affect the timing or outcome of any clinical trials we may conduct, which could prevent completion of these trials and adversely affect our ability to advance the development of our vaccine candidates.

From time to time, we may publish interim topline or preliminary data from our preclinical or clinical trials. Interim topline 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 more patient data become available. 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 when we publish such data. As a result, the topline results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results once additional data have been received and fully evaluated. Preliminary or 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 may publish. As a result, interim and preliminary data should be viewed with caution until the final data are available. Adverse differences between preliminary or interim data and final data could significantly harm our business prospects. Additionally, disclosure of interim topline or preliminary data by us or by our competitors has and may continue to result in volatility in the price of our common stock. Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular vaccine candidate and our company in general. In addition, the information we choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is the material or otherwise appropriate information to include in our disclosure. Any information we determine not to disclose may ultimately be deemed significant by you or others with respect to future decisions, conclusions, views, activities or otherwise regarding a particular vaccine candidate or our business. If the topline data that we report differ from final results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, vaccine candidates may be harmed, which could significantly harm our business prospects.

We have in the past and may in the future seek BTD or Fast Track designation for some of our vaccine candidates. For instance, in August 2022 we announced that the FDA granted Fast Track designation to VAX-24 in adults ages 18 and older, in January 2023 we announced that the FDA granted a BTD for VAX-24 for the prevention of IPD in adults, in November 2024 we announced that the FDA granted a BTD for VAX-31 for the prevention of IPD in adults, and in August 2025 we announced that the FDA extended the BTD for VAX-31 to include the prevention of pneumonia caused by Streptococcus pneumoniae in adults. A sponsor may seek FDA designation of its vaccine candidate as a breakthrough therapy if the vaccine candidate is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the therapy may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For vaccines that have been designated as Breakthrough Therapies, the FDA may take actions to expedite the development and review of the application, and interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. A vaccine designated as a breakthrough therapy by the FDA may also be eligible for expedited review and approval. If a vaccine candidate is intended for the treatment of a serious or life-threatening condition and clinical or preclinical data demonstrate the potential to address unmet medical needs for this condition, the sponsor may apply for Fast Track designation. The FDA has broad discretion whether or not to grant this designation, so even if we believe a particular vaccine candidate is eligible for this designation, we cannot assure you that the FDA would decide to grant it. Even if we obtain Fast Track designation for one or more of our vaccine candidates, we may not experience a faster development process, review or approval compared to non-expedited FDA review procedures. In addition, the FDA may withdraw Fast Track designation from any of our vaccine candidates that may receive the designation in the future, if it believes that the designation is no longer supported. Fast Track designation alone does not guarantee qualification for the FDA's Priority Review procedures. Whether to grant a BTD or Fast Track designation is within the discretion of the FDA. Accordingly, even if we believe one of our vaccine candidates meets the criteria for these designations, the FDA may disagree and instead determine not to make such designation. In any event, the receipt of either of these designations for a vaccine candidate may not result in a faster development process, review or approval compared to vaccine candidates considered for approval under non-expedited FDA review procedures and does not assure ultimate approval by the FDA. In addition, even when one or more of our vaccine candidates qualify for either of these designations, the FDA may later decide that the vaccine candidate no longer meets the conditions for qualification and rescind the designations.