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

We have a limited operating history, have incurred significant net losses since our inception, and anticipate that we will continue to incur significant net losses for the foreseeable future, and such net losses are expected to increase as we continue our clinical development of, and seek regulatory approvals for, our product candidates,candidate, tralesinidase alfa, tildacerfont, SPR202, SPR204TA-ERT, and anyour other current and future product candidates.

Investment in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate effectiveness in the targeted indication or an acceptable safety profile, gain regulatory approval and become commercially viable. We have no products approved for commercial sale and have not generated any product revenue to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. As a result, we are not profitable and have incurred significant net losses since our inception. If our product candidates are not successfully developed and approved, we may never generate any product revenue. For the years ended December 31, 20242025 and 2023,2024, we reported net losses of $53.0$39.0 million and $47.9$53.0 million, respectively. As of December 31, 2024,2025, we had an accumulated deficit of $250.3$289.2 million.

We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase as we continue our clinical development of, seek regulatory approvals for, and commercially launchlaunch, tralesinidaseif alfa,approved, tildacerfontTA-ERT and our other current and future product candidates, if approved.candidates. We may encounter unforeseen expenses, difficulties, complications, delays, and other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenues. Our prior net losses and expected future net losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital. Because of the numerous risks and uncertainties associated with drug development, we are unable to accurately predict the timing or amount of increased expenses, or when, if at all, we will be able to achieve profitability.

The success of tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates will depend on severalvarious factors, including the following:

acceptance by the FDA and EMA of the clinical trial design of our planned and ongoing clinical trials of tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates;

establishing sales, marketing, and distribution capabilities and commercializing tildacerfont,TA-ERT and our other current product candidates, if approved, whether alone or in collaboration with others;

establishing and maintaining patent and trade secret protection and regulatory exclusivity for tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates;

maintaining an acceptable safety profile of tildacerfontTA-ERT and our other current product candidates following approval; and maintaining and growing an organization of people who can develop and, if approved, commercialize, market, and sell tildacerfontTA-ERT and our other current product candidates to physicians, patients, healthcare payors, and others in the medical community.

If we do not achieve one or more of these factors, many of which are beyond our control, in a timely manner or at all, we could experience significant delays or an inability to obtain regulatory approvals or commercialize our product candidates.candidates, if approved.

Even if regulatory approvals are obtained, we may never be able to successfully commercialize our product candidates. In addition, we will need to transition at some point from a company with a development focus to a company capable of supporting commercial activities. We may not be successful in such a transition. Accordingly, we may not be able to generate sufficient revenue through the sale of tildacerfontTA-ERT and our other current product candidates, if approved, to continue our business.

We intend to submit a BLA seeking accelerated approval of TA-ERT for MPS IIIB based on existing clinical data, however there can be no assurance that such submission or application will be accepted for filing by the FDA or that approval will be granted on a timely basis, or at all. For example, in March 2024, in a type C meeting with the FDA, the FDA confirmed that CSF HS-NRE is deemed to be a biomarker reasonably likely to predict clinical benefit and could serve as a basis for accelerated approval. The FDA also confirmed that the completed clinical and nonclinical studies of tralesinidase alfaTA-ERT were sufficient for a biologics license application BLA submission and provided guidance around key design elements of a confirmatory trial (placebo-controlled 5-year study with a 2-year interim analysis in 14 patients), which must be initiated prior to potential accelerated approval of tralesinidase alfa. Based, in part, on these discussions, we intend to submit the BLA for tralesinidase alfa for the treatment of MPSIIIB in the first half of 2026. Failure to obtain accelerated approval would result in a longer time period to commercialization, if any, and would increase the cost of development and harm our competitive position in the marketplace.TA-ERT.

Before obtaining regulatory approvals for the commercial sale of a product candidate, we must demonstrate through lengthy, complex, and expensive preclinical testing and clinical trials that a product candidate is both safe and effective for use in each target indication. Clinical trials often fail to demonstrate safety and efficacy of the product candidate studied for the target indication. Most product candidates that commence clinical trials are never approved by regulatory authorities for commercialization. We are seeking to develop treatments for MPS IIIB, MDD, and congenital adrenal hyperplasia (CAH), and post-bariatric hypoglycemia (PBH). We intend to seek accelerated approval of TA-ERT for MPS IIIB based on existing clinical data. As a condition of seeking such approval of a BLA from the FDA, we will initiate a confirmatory Phase 3 trial, which must be initiated prior to potential accelerated approval of TA-ERT. We intend to submit the BLA for TA-ERT for the treatment of MPS IIIB in the firstfourth halfquarter of 2026.2026, and if successful and FDA approval is received, potentially commercially launch in mid-2027. Additionally, any safety concerns observed in any one of our clinical trials in our targeted indications could limit the prospects for regulatory approval of tralesinidase alfaTA-ERT and tildacerfontour other current product candidates in other indications.

The biopharmaceutical industry is characterized by intense competition and rapid innovation and our competitors may be able to develop other compounds or drugs that are able to achieve similar or better results. Our potential competitors include major multinational pharmaceutical companies, established biotechnology companies, specialty pharmaceutical companies and universities and other research institutions. Many of our competitors have substantially greater financial, technical and other resources, such as larger research and development staff and experienced marketing and manufacturing organizations and well-established sales forces. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies. Mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated in our competitors. Competition may increase further as a result of advances in the commercial applicability of technologies and greater availability of capital for investment in these industries. Our competitors may succeed in developing, acquiring or licensing on an exclusive basis drug products that are more effective or less costly than tralesinidase alfa, tildacerfont, SPR202TA-ERT and SPR204.our other current product candidates. We believe the key competitive factors that will affect the development and commercial success of our product candidates are, among other things:

Preclinical and clinical drug development involves a lengthy and expensive process with uncertain outcomes, and results of earlier studies and trials may not be predictive of future trial results. We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates.

Before obtaining marketing approval from regulatory authorities for the sale of any of our product candidates, we or our collaborators must conduct extensive trials to demonstrate the safety and efficacy of the product candidates in humans. Preclinical and clinical testing is expensive and difficult to design and implement, can take many years to complete, and its outcome is inherently uncertain. A failure of one or more preclinical or clinical trials can occur at any stage of testing. The results of preclinical studies and early clinical trials of tralesinidase alfaTA-ERT and tildacerfont, and preclinical studies of SPR202 and SPR204 may not be predictive of the results of later-stage clinical trials, and interim results of a trial do not necessarily predict final results. Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials. For example, we plan to use doses in our clinical trials for tralesinidase alfaTA-ERT and tildacerfont that may not be safe or efficacious doses. As such, our hypotheses of efficacy may not show the desired clinical results. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or safety profiles, notwithstanding promising results in earlier trials. Moreover, preclinical and clinical data is often susceptible to varying interpretations and analyses. WeFor example, we have faced significant setbacks as we conducted our two Phase 2b clinical trials for tildacerfont in adult patients with classic CAH, and we may continue to face such setbacks in our other development programs, which may delay or prevent regulatory approval of tildacerfont. For example, due to not meeting its primary efficacy endpoint, we terminated our CAHmelia-203 trial in March 2024 and our CAHmelia-204 trial in December 2024. Additionally, the TAMARIND Phase 2 study of tildacerfont in MDD was discontinued in the first quarter of 2026 following a serious adverse event in which a patient experienced a significant elevation of liver enzymes. The prior sponsor of tralesinidase alfa,TA-ERT, Allievex, discontinued clinical development due to financial constraints.

We may not be able to initiate or continue our clinical trials for tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates if we are unable to identify and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA and comparable foreign regulatory authorities. Patient enrollment, a significant factor in the timing of clinical trials, is affected by many factors including the size and nature of the patient population especially in the case of an orphan indication, the proximity of patients to clinical sites, competition with other organizations or our own clinical trials for clinical trial sites or patients, the eligibility and exclusion criteria for the clinical trial, the design of the clinical trial, competing clinical trials, patient engagement, and clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new drugs that may be approved for the indications we are investigating.

In particular, one indication for which we are evaluating tralesinidase alfaTA-ERT is a rare neurodegenerative pediatric disorder with limited patient populations from which to draw participants in clinical trials. For example, we estimate the MPS-IIIB population in the United States is less than 200 patients. We are and will be required to identify and enroll a sufficient number of patients with the disorder under investigation for our clinical trials of tralesinidase alfa.TA-ERT. Potential patients may not be adequately diagnosed or identified with the disorders which we are targeting or may not meet the entry criteria for our clinical trials. Additionally, other pharmaceutical companies with more resources and greater experience in drug development and commercialization are targeting these same disorders and are recruiting clinical trial patients from these patient populations, which may delay or make it more difficult to fully enroll our clinical trials. Our inability to enroll a sufficient number of patients for any of our current or future clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether.

acceptance by the FDA and EMA of the clinical trial design of our planned and ongoing clinical trials of tralesinidase alfaTA-ERT and tildacerfontour other current product candidates;

manufacturing sufficient quantities of tralesinidase alfa, tildacerfontTA-ERT or our other current and future product candidates or obtaining sufficient quantities of combination therapies for use in clinical trials;

subjects choosing an alternative treatment for the indications for which we are developing tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates, or participating in competing clinical trials;

lack of adequate funding to continue the clinical trial, such as that experienced by Allievex in relation to the continued development of tralesinidase alfaTA-ERT;

Further, conducting clinical trials in foreign countries, which we have done for TA-ERT, are doing for tildacerfont and may do for any future product candidates, presents additional risks that may delay completion of our clinical trials. These risks include the failure of enrolled patients in foreign countries to adhere to clinical protocol as a result of differences in healthcare services or cultural customs, managing additional administrative burdens associated with foreign regulatory schemes, as well as political and economic risks relevant to such foreign countries.

Moreover, principal investigators for our clinical trials may serve and have served 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 authority may conclude that a financial relationship between us and a principal investigator has created a conflict of interest or otherwise affected interpretation of the trial. The FDA or comparable foreign regulatory authority 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 authority, as the case may be, and may ultimately lead to the denial of marketing approval of tildacerfont.TA-ERT or our other current and future product candidates.

If we experience delays in the completion of, or termination of, any clinical trial of tralesinidase alfa, tildacerfontTA-ERT or our other current and future product candidates, the commercial prospect of tralesinidase alfa, tildacerfontTA-ERT or our other current and future product candidates will be harmed, and our ability to generate product revenue will be delayed. Moreover, any delays in completing our clinical trials will increase our costs, slow down our product candidate development and approval process and jeopardize our ability to commence product sales and generate revenue. In addition, many of the factors that cause, or lead to, termination or suspension of, or a delay in the commencement or completion of, clinical trials may also ultimately lead to the denial of regulatory approval of tralesinidase alfa, tildacerfontTA-ERT or our other current and future product candidates. Further, delays to our clinical trials that occur as a result could shorten any period during which we may have the exclusive right to commercializecommercialize, tralesinidaseif alfaapproved, TA-ERT and tildacerfontour other current product candidates, and our competitors may be able to bring products to market before we do, and the commercial viability of tralesinidase alfaTA-ERT and tildacerfontour other current product candidates could be significantly reduced. Any of these occurrences may harm our business, financial condition, results of operations and prospects significantly.

Tralesinidase alfa and tildacerfont are,TA-ERT and our other current and future product candidates will be,be subject to extensive regulation and compliance obligations, which are costly and time-consuming, and such regulation may cause unanticipated delays or prevent the receipt of the required approvals to commercialize tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates.

The clinical development, manufacturing, labeling, storage, record-keeping, advertising, promotion, import, export, marketing, and distribution of our product candidates subject to extensive regulation by the FDA in the United States and by comparable foreign regulatory authorities in foreign markets. In the United States, we are not permitted to market tralesinidase alfa, tildacerfontTA-ERT or any other current or future product candidates until we receive regulatory approval from the FDA. The process of obtaining regulatory approval is expensive, often takes many years following the commencement of clinical trials and can vary substantially based upon the type, complexity, and novelty of the product candidates involved, as well as the target indications and patient population. Approval policies or regulations may change, and the FDA has substantial discretion in the drug approval process, including the ability to delay, limit, or deny approval of a product candidate for many reasons. Despite the time and expense invested in clinical development of product candidates, regulatory approval is never guaranteed. Neither we nor any future collaborator is permitted to market tralesinidase alfa, tildacerfontTA-ERT or any other current or future product candidates in the United States until we receive approval of an NDA or BLA from the FDA. Similar requirements and risks are applicable in foreign markets. We have not previously submitted an NDA or BLA to the FDA, or similar drug approval filings to comparable foreign authorities.

Prior to obtaining approval to commercialize a product candidate in the United States or in foreign markets, we must demonstrate with substantial evidence from adequate and well-controlled clinical trials, and to the satisfaction of the FDA or comparable foreign regulatory authorities, that such product candidates are safe and effective for their intended uses. Results from non-clinical studies and clinical trials can be interpreted in different ways. Even if we believe the non-clinical or clinical data for our product candidates are promising, such data may not be sufficient to support approval by the FDA and comparable foreign regulatory authorities. The FDA or comparable foreign regulatory authorities, as the case may be, may also require us to conduct additional preclinical studies or clinical trials for tralesinidase alfa, tildacerfontTA-ERT and any other current and future product candidates either prior to or post-approval, or may object to elements of our clinical development program.

Tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates could fail to receive regulatory approval for many reasons, including the following:

serious and unexpected drug-related side effects may be experienced by participants in our clinical trials or by people using drugs similar to tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates;

Any of the above events could prevent us from achieving market approval of tralesinidase alfa, tildacerfontTA-ERT or our other current and future product candidates and could substantially increase the costs of commercializing tralesinidase alfa, tildacerfontTA-ERT or our other current and future product candidates. The demand for tralesinidaseTA-ERT alfa,and tildacerfontour other current or any future product candidates could also be negatively impacted by any adverse effects of a competitor’s product or treatment.

Of the large number of drugs in development, only a small percentage successfully complete the FDA or foreign regulatory approval processes and are commercialized. The lengthy approval process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval to market tildacerfontTA-ERT and our other current and future product candidates, which would significantly harm our business, financial condition, results of operations, and prospects.

Even if we eventually complete clinical trials and receive approval of an NDA, BLA or foreign marketing application for tralesinidase alfa, tildacerfontTA-ERT and our other current and future product candidates, the FDA or comparable foreign regulatory authority may grant approval contingent on the performance of costly additional clinical trials, including Phase 4 clinical trials, and/or the implementation of a risk evaluation and mitigation strategy (“REMS”) or comparable foreign strategies which may be required to ensure safe use of the drug after approval. The FDA or the comparable foreign regulatory authority also may approve a product candidate for a more limited indication or patient population than we originally requested, and the FDA or comparable foreign regulatory authority may not approve the labeling that we believe is necessary or desirable for the successful commercialization of a product. Any delay in obtaining, or inability to obtain, applicable regulatory approval would delay or prevent commercialization of that product candidate and would materially adversely impact our business and prospects.

Further, others, including regulatory authorities, 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 product candidate or product 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, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product, product candidate, or our business. If the interim, topline, or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain regulatory approval for, and commercialize, our product candidates and any future product candidates may be harmed, which could harm our business, operating results, prospects, or financial condition.condition, results of operations and prospects.

Since our inception in November 2014, we have focused primarily on raising capital, establishing and protecting our intellectual property portfolio, organizing and staffing our company, business planning, and conducting preclinical and clinical development of, and manufacturing development for, our product candidate, tildacerfont. We have no products approved for commercial sale and have not generated any product revenue to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. Our ability to generate product revenue sufficient to achieve profitability, if ever, will depend on the successful development of tildacerfontTA-ERT and anyour other current and future product candidates.

Since inception through December 31, 2024,2025, we have raised aggregate gross proceeds of $293.1$343.1 million, including $103.5 million from our initial public offering (“IPO”) in October 2020, $116.0 million from the sale of our redeemable convertible preferred stock, $5.0 million from the issuance of debt, $53.6 million from a private placement financing in February 2023, and the $15.0 million upfront payment from Kaken Pharmaceutical Co. Ltd. received in April 2023.2023, and $50.0 million from a private placement financing in October 2025. As of December 31, 2024,2025, we had cash and cash equivalents of $38.8$48.9 million.

Without alternative financing or proceeds from other strategic alternatives, we believe, based on our current operating plan, that our cash and cash equivalents as of December 31, 20242025 and gross proceeds received in January 2026 under the Loan Agreement with Avenue Capital (each as defined below) will be insufficient to fund our operations and debt obligations for at least 12 months following the issuance date of our financial statements included elsewhere in this Annual Report.

pursue regulatory approval of TA-ERT in patients with MPSIIIBMPS IIIB;

advance TA-ERT through a planned confirmatory study in patients with MPSIIBMPS IIIB and expanded access programs;

expand manufacturing capacity to accommodate anticipated global demand of TA-ERT, if approved, for the treatment of MPSIIIBMPS IIIB;

advance pre-clinical and clinical development of SPR202 in congenital adrenal hyperplasia (“CAH”);

Global economic and business activities continue to face widespread macroeconomic uncertainties, including recentglobal andtrade potential future disruptions in access to bank deposits or lending commitments due to bank failures,disputes, labor shortages, declines in consumer confidence, inflation and monetary supply shifts, recession risks andrisks, potential disruptions from the ongoing wars in Ukraine and the Middle East and related sanctions.sanctions, declines in economic growth, tariffs and related legal challenges, and uncertainty about economic stability.

Loan Agreement with SiliconAvenue Valley BankCapital

To date, all of our revenue has been derived from a collaboration and license agreement (the “Kaken License Agreement,Agreement”) with Kaken Pharmaceutical Co. Ltd. (“Kaken”), pursuant to which we granted Kaken the exclusive right to develop and commercialize tildacerfont for CAH in Japan.

We will recognize royalty and milestone revenues under the Kaken License Agreement if and when appropriate under the relevant accounting rules (see Note 8 to our financial statements). We have not generated any revenues from the commercial sale of approved products and we do not expect to generate revenues from the commercial sale of our product candidates for at least the foreseeable future, if ever.

To date, these expenses have been incurred primarily to advance tildacerfont and acquire and develop TA-ERT. These expenses will primarily consist of personnel costs, expenses for the conduct of clinical trials, manufacturing costs for clinical drug supply, and in-process research and development. We expect that significant additional spending will be required to progress TA-ERT through clinical development and potential regulatory approval and advancing our other investigational product candidates through clinical and pre-clinical development.

We expect that our general and administrative expenses will continue to increase in the foreseeable future as additional administrative personnel and services are required to manage these functions of a public company, and as we advance tildacerfontTA-ERT through clinical development and potential regulatory approval.

Interest expense consists of interest incurred and non-cash amortization of debt discount and issuance costs in connection with the Termdebt Loan.previously outstanding with Silicon Valley Bank, which we voluntarily prepaid in full on November 3, 2025.

Interest and other income, net primarily consists of interest income earned on our cash,cash and cash equivalents and investments.equivalents.

During the yearsyear ended December 31, 2024 and 2023, we recognized $4.9 million and $10.1 million, respectively, as collaboration revenue under the Kaken License Agreement.

The increasedecrease in manufacturing expenses of $3.9$5.1 million was primarily driven by manufacturing costs related to one-time expenses incurred in connection with the AllievexTA-ERT assetdevelopment purchaseprogram of $5.9 million, partially offset by a decrease of $1.0$3.5 million related toand the terminationdiscontinuation of the CAHmelia-203tildacerfont study.CAH development program of $1.5 million.

TheThere was also a decrease in personnel relatedpersonnel-related expenses of $1.5$5.5 million wasdue primarily driven byto a decrease of $1.3 million in salaries due to reduced headcount, partiallyincluding offseta by an increase of $0.5 milliondecrease in stock-based compensation expense.expense of $2.1 million.

General and administrative expenses increased by $2.0$2.3 million during the year ended December 31, 20242025 compared to the year ended December 31, 2023,2024, primarily due to an increase in professional fees of $2.5$3.1 millionmillion, indriven by patent litigation and other legal professional services, partiallycosts, offset by a decrease in stock-based compensation expense of $0.3$0.7 million in insurance costs for directors and officers.million.

Interest expense decreased by $0.2 million during the year ended December 31, 20242025 compared to the year ended December 31, 20232024 due to the decrease in the interest rate and the decrease in the principal balance on the Termdebt Loanpreviously outstanding with Silicon Valley Bank year over year.

Interest and other income, net decreased by $1.1$2.3 million during the year ended December 31, 20242025 compared to the year ended December 31, 20232024, primarily due to a decrease in cashinterest andincome cashof equivalents$2.3 yearmillion overprimarily year.due to lower average daily balances earning yield in money market accounts.

Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from operations. We anticipate that we will continue to incur net losses for the foreseeable future. As of December 31, 2024,2025, we had an accumulated deficit of $250.3$289.2 million. As of December 31, 2024,2025, we had cash and cash equivalents of $38.8$48.9 million. Since inception through December 31, 2024,2025, we have raised aggregate gross proceeds of $293.1$343.1 million, including $103.5 million from our IPO in October 2020, $116.0 million from the sale of our redeemable convertible preferred stock, $5.0 million from the issuance of debt, $53.6 million from a private placement financing in February 2023, and $15.0 million from the Kaken upfront payment received in April 2023.2023, and $50.0 million from a private placement financing in October 2025.

Until we can generate sufficient revenue, if ever, to fund our operations, we will need to finance future cash needs through public or private equity offerings, license agreements, debt financings or restructurings, collaborations, strategic alliances and marketing or distribution arrangements, and there can be no assurance that such arrangements will be available to us on a timely basis, or, if available, will be available on terms acceptable to us. Without alternative financing or proceeds from other strategic alternatives, we believe, based on our current operating plan, that our cash and cash equivalents as of December 31, 20242025 and gross proceeds received in January 2026 under the Loan Agreement with Avenue Capital will be insufficient to fund our operations and debt obligations for at least 12 months following the issuance date of our financial statements included elsewhere in this Annual Report. These conditions raise substantial doubt about our ability to continue as a going concern.

To date, we have not generated any product revenue. We do not expect to generate any meaningful revenue unless and until we obtain regulatory approval and commercialize TA-ERT or any other current or future product candidates, and we do not know when, or if at all, that will occur. We will continue to require additional capital to develop tildacerfontTA-ERT and fund operations for the foreseeable future. Our primary uses of cash are to fund our operations, which consist primarily of research and development expenses related to our clinical development programs, and to a lesser extent, general and administrative expenses.

At this time, we cannot reasonably estimate or know the nature, timing, and estimated costs of the efforts that will be necessary to complete the development of, and obtain regulatory approval for, tildacerfontTA-ERT or any of our other current or future product candidates. We expect our research and development expenses to increase significantly in the foreseeable future as we continue to invest in activities related to the clinical development and commercialization of TA-ERT,TA-ERT and as we pursue regulatory approval of TA-ERT for the treatment of MPSIIIB.MPS IIIB. The process of conducting the necessary clinical research to obtain regulatory approval is costly and time-consuming, and we may never succeed in achieving regulatory approval for TA-ERT in patients with MPSIIIB.MPS IIIB.

the economic and other terms, timing of, and success of any collaboration, licensing, or other arrangements which we may enter in the future; and the effects of the disruptions to and volatility in the credit and financial markets in the United States and worldwide from geopolitical and macroeconomic events, including global trade disputes, labor shortages, declines in consumer confidence, inflation and monetary supply shifts, recession risks, tariffs and related legal challenges, and the ongoing wars in Ukraine and Israelthe Middle East and related sanctions, and recent and potential future disruptions in access to bank deposits or lending commitments due to bank failures.sanctions.

We may be unable to raise additional funds or to enter into such agreements or arrangements on favorable terms, or at all. Our ability to raise additional funds may be adversely impacted by potential worsening global economic conditions and the disruptions to, and volatility in, the credit and financial markets in the United States and worldwide resulting from macroeconomic events, global trade disputes, labor shortages, declines in consumer confidence, inflation and monetary supply shifts, recession risks, potential disruptions from the wars in Ukraine and Israelthe Middle East and related sanctions, and recent and potential future disruptions in access to bank deposits or lending commitments due to bank failures, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increasestariffs inand unemploymentrelated rates,legal challenges, and uncertainty about economic stability. If the equity and credit markets continue to deteriorate, it may make any necessary debt or equity financing more difficult, more costly and more dilutive. If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may have to significantly delay, scale back, or discontinue the development or commercialization of our product candidates or other research and development initiatives. We also could be required to seek collaborators for our product candidates and any future product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available or relinquish or license on unfavorable terms our rights to our product candidates and any future product candidates in markets where we otherwise would seek to pursue development or commercialization ourselves.

As of December 31, 2024,2025, the total undiscounted lease payments for our non-cancelable operating lease for office space, which terminates in February 2028 unless renewed, was $1.2$0.8 million. On January 7, 2026, we entered into the Loan Agreement with Avenue Capital, which makes available to us term loans in an aggregate principal amount of up to $50.0 million, subject to the company’s achievement of certain regulatory milestones. As of the date hereof, $15.0 million has been funded under the Loan Agreement.

We enter into contracts in the normal course of business with third-party contract manufacturing organizations and CROs for clinical trials, non-clinical studies, drug substance and product manufacturing and other services for operating purposes. These contracts are generally cancelable by us upon prior written notice after a certain period.period, except for certain contracts with contract manufacturing organizations containing minimum purchase obligations. Payments due upon cancellation consist only of payments for services provided or expenses incurred, including noncancelable obligations of our service providers, up to the date of cancellation.

Net cash used in operating activities increaseddecreased by $22.7$22.6 million during the year ended December 31, 20242025 compared to the year ended December 31, 2023. Net cash used in fiscal 2024 includesprimarily cashdue paidto of $10.6 million for the Allievex asset purchase which was offset by a decrease inlower payments driven by thedecreased terminationclinical ofdevelopment the CAHmelia-203 study and completion of the studies for CAHmelia-204, CAHmelia-205 and POWER. Additionally, cash used in fiscal 2023 wasactivities offset by thepayments receiptmade for asset acquisitions of the$7.4 $15.0 million upfront payment under the Kaken License Agreement in April 2023.million.

As of MarchJune 31,30, 2026, we had cash and cash equivalents of $54.1$96.3 million. In October 2020, we consummated our initial public offering and issued 92,000 shares of common stock for net proceeds of $93.4 million. In February 2023, we completed a private placement for net proceeds of $50.9 million. In April 2023, we received a $15.0 million upfront payment under a collaboration and license agreement with Kaken Pharmaceutical Co. Ltd. In October 2025, we entered into a Securities Purchase Agreement with certain institutional investors to sell and issue (i) 502,181 shares of common stock and (ii) pre-funded warrants to purchase up to 233,144 shares of common stock incompleted a private placement transaction, which were exercised in full by December 31, 2025. Ourfor total net proceeds wereof $46.6 million. On January 7, 2026, we entered into the Avenue Loan Agreement, which makes available to the company term loans in an aggregate principal amount of up to $50.0 million, subject to the company’s achievement of certain regulatory milestones, which we may not achieve. Additionally, onOn April 22, 2026, we closed our previously announced underwritten public offering of 1,150,000 shares of our common stock and pre-funded warrants to purchase up to 50,000 shares of our common stock, and we granted the underwriters a 30-day option to purchase up to 180,000 additional shares of common stock, which was exercised in full. The grossnet proceeds to us from the offering were approximately $69.0$64.4 million. Additionally, in August 2026 we completed a private placement for gross proceeds of $5.5 million.

We are a late-stage biopharmaceutical company foundedincorporated in 2014,2016, and our operations to date have focused primarily on raising capital, establishing and protecting our intellectual property portfolio, organizing and staffing our company, business planning, and conducting preclinical and clinical development of, and manufacturing development for, our product candidates. Additionally, 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. As we build our capabilities and expand our organization, we have not yet demonstrated an ability to overcome many of the risks and uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly in the biopharmaceutical area. Consequently, any predictions about our future performance may not be as accurate as they would be if we had a history of successfully developing and commercializing biopharmaceutical products.

Investment in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate effectiveness in the targeted indication or an acceptable safety profile, gain regulatory approval and become commercially viable. We have no products approved for commercial sale and have not generated any product revenue to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. As a result, we are not profitable and have incurred significant net losses since our inception. If our product candidates are not successfully developed and approved, we may never generate any revenue. For the threesix months ended MarchJune 31,30, 2026 and 2025, we reported net losses of $12.3$28.5 million and $14.0$16.1 million, respectively. As of MarchJune 31,30, 2026, we had an accumulated deficit of $301.5$317.7 million.

receipt of marketing approvals from applicable regulatory authorities, including one or more new drug applications (“NDAs”) from the FDA,authorities and maintaining such approvals;

We also held two Type B meetings with the FDA ahead of our anticipated BLA submission for TA-ERT; the first in December 2025 to discuss our clinical data and regulatory strategy, and the second in January 2026 to discuss CMC requirements. During the December 2025 meeting, the FDA confirmed that the integrated study data from interventional clinical studies of TA-ERT and the available natural history data could potentially serve as an adequate and well-controlled study for purposes of the FDA’s review of the effects of TA-ERT on CSF HS-NRE, which could serve as a RLSEsurrogate endpoint to support an accelerated approval. Following the January 2026 CMC meeting, the FDA considered the company’s plan to address DP PPQ batch requirements for the BLA submission, and in the official meeting minutes, the FDA shared its requirement for one DP PPQ batch at the time of BLA submission and data from a second DP PPQ batch prior to midcycle of BLA review.

Based, in part, on these discussions, we intend to submit the BLA for TA-ERT for the treatment of MPS IIIB in the fourth quarter of 2026, and if successful and FDA approval is received, potentially commercially launch in mid-2027. However, even if we submit the BLA as planned, we may be unsuccessful in providing sufficient evidence of CSF HS-NRE as a RLSE to predict clinical benefit in support of an accelerated approval, and after reviewing our BLA submission, the FDA may ultimately reject CSF HS-NRE asissue a RLSE.Complete Response Letter. For example, the FDA has in the past rejected accelerated approval following submission of a BLA under accelerated approval pathway by another company focusing on the treatment of an ultra-rare neurodegenerative disease, in part due to uncertainty regarding the appropriateness of the designatedproposed RLSE,surrogate endpoint, and the FDA may reject similar BLA applications in the future. If our BLA submission is viewed as having similarities to another BLA submission that was previously rejected by the FDA, this could impact the likelihood of success of our BLA application or could influence investor perception of our likelihood of success, which could cause the price of our common stock to decline, and could harm our business, financial condition, results of operations and prospects. If the FDA rejects CSF HS-NRE as a RLSE,surrogate endpoint, we may be required to conduct longer-term follow up, to enroll additional patients in our current study, or to perform a new clinical study, all of which could be challenging with an ultra-rare and fatal genetic disease like MPS IIIB and could make us experience significant delays in, or could prevent us from, obtaining accelerated regulatory approval. Failure to obtain accelerated approval would result in a longer time period to commercialization, if any, and would increase the cost of development and harm our competitive position in the marketplace.

The clinical development, manufacturing, labeling, storage, record-keeping, advertising, promotion, import, export, marketing, and distribution of our product candidates subject to extensive regulation by the FDA in the United States and by comparable foreign regulatory authorities in foreign markets. In the United States, we are not permitted to market TA-ERT or any other current or future product candidates until we receive regulatory approval from the FDA. The process of obtaining regulatory approval is expensive, often takes many years following the commencement of clinical trials and can vary substantially based upon the type, complexity, and novelty of the product candidates involved, as well as the target indications and patient population. Approval policies or regulations may change, and the FDA has substantial discretion in the drug approval process, including the ability to delay, limit, or deny approval of a product candidate for many reasons. Despite the time and expense invested in clinical development of product candidates, regulatory approval is never guaranteed. Neither we nor any future collaborator is permitted to market TA-ERT or any other current or future product candidates in the United States until we receive approval of ana new drug application (“NDA”) or BLA from the FDA. Similar requirements and risks are applicable in foreign markets. We have not previously submitted an NDA or BLA to the FDA, or similar drug approval filings to comparable foreign authorities.

the data collected from clinical trials may not be sufficient to satisfy the FDA or comparable foreign regulatory authorities to support the submission of an NDA, BLA or other comparable submissions in foreign jurisdictions or to obtain regulatory approval in the United States or elsewhere, requiring, in the case of adult patients with classic CAH, additional clinical trials beyond our ongoing Phase 2b clinical trial prior to any such approvalelsewhere;

We operate in a global economy, which includes utilizing third-party suppliers in several countries outside the United States. There is inherent risk, based on the complex relationships among the United States and the other countries in which we conduct our business, that political, diplomatic, and national security factors can lead to global trade restrictions and changes in trade policies and export regulations that may adversely affect our business and operations. The current international trade and regulatory environment is subject to significant ongoing uncertainty. The U.S. government has announced imposition of substantial tariffs affecting a wide range of products and jurisdictions and has indicated an intention to continue developing new trade policies, including with respect to the pharmaceutical industry. In response, certain foreign governments have announced or implemented retaliatory tariffs and other protectionist measures. These developments, including legal challenges to such tariffs, have created a dynamic and unpredictable trade landscape, which may adversely impact our business, results of operations, financial condition and prospects. The Bureau of Industry and Security, U.S. Department of Commerce, has initiated an investigation to determine whether pharmaceutical ingredients, including finished drug product, manufactured outside the United States, pose a national security risk and should be subject to additional tariffs. Based on this investigation, on April 2, 2026, the President issued a proclamation imposing up to a 100% tariff on certain patented pharmaceuticals and associated pharmaceutical ingredients. These tariffs will become effective September 29, 2026, unless they are “expressly reduced, modified, or terminated.”

The current administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, the Centers for Medicare & Medicaid Services (“CMS”) and related agencies. These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business. For example, the current administration has announced agreements with severalcertain pharmaceutical companies that require the drug manufacturers to offer, through a direct to consumer platform (“TrumpRx”), U.S. patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues. Other recent actions, for example, include (1) directives to reduce agency workforce and cut programs; (2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products; (3) imposing tariffs on certain imported pharmaceutical products; and (4) as part of the Make America Healthy Again (“MAHA”) Commission’s recent Strategy Report, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising. Additionally, the current administration recently called on Congress to enact “The Great Healthcare Plan,” to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager, or PBM, payment methodologies, among other things. These actions and policies may significantly reduce U.S. drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks. In June 2024, the U.S. Supreme Court’s Loper Bright Enterprises v. Raimondo decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations. Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our product candidates, if approved.

In addition, certain foreign activities related to drugs, biologics, and research, especially with regard to China, have come under increased scrutiny in the United States. Chinese contract manufacturing organizations may become subject to legislation, trade restrictions, sanctions, tariffs and other regulatory requirements by the U.S. government, which could restrict or even prohibit our ability to work with such entities. For example, on December 10,18, 2025, President Trump signed the National Defense Authorization Act for Fiscal Year 2026 (“NDAA”) passedinto overwhelminglylaw. inOn June 8, 2024, the U.S. HouseDepartment of RepresentativesDefense (the “House”) and includesreleased the BIOSECUREannual Act1260H which,List inwhich itsincluded currenta form,number wouldof prohibitcontract themanufactures, U.S.making governmentthem from procuring biotechnology equipment or services from “biotechnology companies of concern,”concern. andThe wouldBIOSECURE prohibitAct prohibits U.S. governmentfederal contracts,agencies loansfrom andentering grantsinto toor renewing any contract, loan, or grant with any entity that uses biotechnology equipment or services fromproduced or provided by a designated “biotechnology company of concern.concern” to perform that contract. The BIOSECURE Act also prohibits U.S. government loan and grant recipients from using federal loan or grant money to enter into contracts with entities that use equipment from “Biotechnologybiotechnology companies of concern” in the performance of any federal prime contract or subcontract. The Office of Management and Budget (“OMB”) of the U.S. Government will issue a list of “biotechnology companies of concern,” which will include certain companies that are identified on the U.S. Department of Defense’s “annual List of Chinese militaryMilitary companiesCompanies, operatingalso inknown theas United States” list (the 1260H List)List, andother alsoentities authorizeswhich the U.S. governmentGovernment has deemed as such pursuant to identifya additionalseparate designation process, and certain subsidiary, parent, and successor entities forof inclusionthe asforegoing. The BIOSECURE Act includes a safe harbor provision providing that the restrictions do not apply to equipment or services that were formerly but are no longer provided by a “biotechnology companiescompany of concern.” The U.S.BIOSECURE SenateAct hasalso sinceincludes passeda grandfathering provision providing that the prohibitions shall not apply for a five-year period to biotechnology equipment or services produced or provided under a contract or agreement entered into before the applicable effective date. Under the NDAA and on December 18, 2025, President Trump signed the NDAA into law. Under the BIOSECURE Act,Act related language we may be restricted in our ability to work with certain Chinese biotechnology manufacturing companies to the extent we would contract with, or otherwise receive funding from, the U.S. government. In addition, if we, our suppliers, or our customers were to be designated under the NDAA BIOSECURE Act,Act related language, this could potentially cause harm to our business, financial condition, results of operations and prospects.

As of MarchJune 31,30, 2026, we had 1422 employees, all of whom are full-time. As our development and commercialization plans and strategies develop, and as we transition into operating as a public company, we expect to need additional development, managerial, operational, financial, sales, marketing, and other personnel. Future growth would impose significant added responsibilities on members of management, including:

Under the Tax Cuts and Jobs Act of 2017 (“Tax Act”), as modified by the Coronavirus Aid, Relief, and Economic Security Act (“CARES Act”), federal NOL carryforwards generated in tax years beginning after December 31, 2017 may be carried forward indefinitely but may only be used to offset 80% of our taxable income annually. Similar rules may apply under state tax laws. Such limitations could result in the expiration of our carryforwards before they can be utilized and, if we are profitable, our future cash flows could be adversely affected due to our increased taxable income or tax liability. Our NOLs and tax credit carryforwards are subject to review and possible adjustment by the Internal Revenue Service and state tax authorities and may become subject to annual limitations under Section 382 and 383 of the Internal Revenue Code of 1986, as amended. Under Section 382, certain cumulative changes in the ownership interest of significant stockholders over a rolling three-year period in excess of 50 percentage points (by value), could result in an ownership change that may limit our ability to utilize our NOL carryforwards and other tax attributes to offset future taxable income or tax liabilities. An ownership change analysis covering periods through December 31, 2025 concluded that an ownership change occurred in May 2016, August 2020, and October 2025. As a result of the ownership changes, we derecognized NOL-related deferred tax assets down to the amount expected to be realized. Our ability to use our remaining NOL carryforwards may be further limited if we experience a Section 382 ownership change as a result of future changes in our stock ownership. As of MarchJune 31,30, 2026, we recorded a full valuation allowance on our net deferred tax assets.

the size and growth, if any, of the markets for MPS IIIB, major depressive disorder,IIIB and other disorders that we may target;

Sales of a substantial number of shares of our common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock. As of MarchJune 31,30, 2026, there were 1,372,2782,752,810 shares of our common stock outstanding.

In February 2023, we entered into a securities purchase agreement with several institutional and accredited investors, including holders of more than 5% of our total common stock outstanding on the date of the securities purchase agreement, pursuant to which we issued and sold 214,873 shares of common stock, pre-funded warrants to purchase 10,666 shares of common stock, and warrants to purchase 169,147 shares of common stock. All of the pre-funded warrants have been exercised. Additionally, in October 2025, we entered into a securities purchase agreement with certain institutional investors, pursuant to which we agreed to sell and issue 502,181 shares of common stock and pre-funded warrants to purchase up to 233,144 shares of common stock in a private placement transaction. Pursuant to the securities purchase agreements, we have registered for resale such securities. In December 2025, three holders of pre-funded warrants to purchase shares of common stock exercised those warrants to purchase 233,144 shares of common stock. On January 7, 2026, we also entered into the Avenue Loan Agreement, pursuant to which we issued a warrant to purchase $3.2 million in shares of common stock at a price of $50.00 per share. Lender may also elect to convert up to $4.0 million of the principal amount outstanding under the Avenue Loan Agreement into shares of our common stock at a price of $60.00 per share. In August 2026, we entered into a stock purchase agreement pursuant to which we agreed to sell and issue 121,203 shares of common stock in a private placement transaction. If these additional shares of common stock, and the shares of common stock issued or issuable pursuant to such pre-funded warrants and warrants, are resold, or if it is perceived that they will be resold, in the public market, the trading price of our common stock could decline.

We expect that we will need significant additional capital in the future to continue our planned operations, including conducting clinical trials, commercialization efforts, expanded research and development activities, and costs associated with operating a public company. To raise capital, we may sell common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner we determine from time to time, including through the registration statement on Form S-3, declared effective in November 2025, covering the sale of up to $300.0 million of our securities (the “Shelf Registration”). For example, in March 2026, we entered into an Open Market Sales AgreementSM (the “Sales Agreement”) with Jefferies LLC (“Jefferies”), pursuant to which we may elect to issue and sell, from time to time, shares of common stock having an aggregate offering price of up to $75.0 million under the Shelf Registration through Jefferies acting as the sales agent and/or principal. As of MarchJune 31,30, 2026, we have not issued any shares of common stock pursuant to the Sales Agreement. Additionally, on April 22, 2026, we closed our previously announced underwritten public offering of 1,150,000 shares of our common stock and pre-funded warrants to purchase up to 50,000 shares of our common stock. In addition, we granted the underwriters a 30-day option to purchase up to 180,000 additional shares of common stock, which was exercised in full. The grossnet proceeds to us from the offering, beforeafter deducting underwriting discounts and commissions and estimated offering expenses payable by us, were approximately $69.0$64.4 million. As described in the section titled “Risk Factors—Sales of a substantial number of shares of our common stock in the public market could cause our stock price to fall” above, we have in the past entered into transactions where we issued and sold common stock, pre-funded warrants and common warrants to purchase shares of our common stock, and we may enter into other or similar transactions in the future. If we sell additional shares of common stock, convertible securities or other equity securities, investors may be materially diluted by subsequent sales. Such sales may also result in material dilution to our existing stockholders, and new investors could gain rights, preferences and privileges senior to the holders of our common stock.

Presently we have intellectual property rights, through licenses from third parties including Lilly,parties, related to our product candidates. Because our program may require the use of additional proprietary rights held by third parties, the growth of our business will likely depend in part on our ability to acquire, in-license or use these proprietary rights. In addition, our product candidates may require specific formulations to work effectively and efficiently and these rights may be held by others. We may be unable to acquire or in-license, on reasonable terms, proprietary rights related to any compositions, formulations, methods of use, processes or other intellectual property rights from third parties that we identify as being necessary for our product candidates. Even if we are able to obtain a license to such proprietary rights, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. In that event, we may be required to expend significant time and resources to develop or license replacement technology.

Third parties may also raise similar claims before the USPTO, even outside the context of litigation or infringement. Such mechanisms could include re-examination, post-grant review, inter partes review, derivation proceedings, and equivalent proceedings in foreign jurisdictions (e.g., opposition proceedings). For example, we wereare a party to anthree oppositionpost-grant proceedingreview (PGR) proceedings with the EuropeanUnited States Patent Office with respect to EPU.S. Patent No.Nos. 3,784,233,12,576,084, 12,569,490, and 12,569,491. As another example, we were a Revocationparty Proceedingto potential revocation proceedings with respect to EPAustralian Patent No.Nos. 3,784,233 (the “’233 Patent”),2019260793 and a2021324839. UnifiedThese PatentAustralian Courtpatents (UPC)have Revocation Proceeding with respect to EP Patent No. 3,784,233. Oral proceedings took place on November 25, 2025, and on December 16, 2025, the Opposition Division issued a Decision of the Opposition Division stating the ’233 Patent isbeen revoked. The Decision of the Opposition Division may be appealed by filing a notice of appeal and grounds of appeal with the EPO’s Boards of Appeal, due within a non-extendable period of two months and four months respectively from the date of the written decision. We may be subject to new or additional third-party pre-issuance submission of prior art to the USPTO or become involved in other post-grant review procedures, derivations, reexaminations, or inter partes review proceedings, in the United States or oppositions or similar proceedings in foreign jurisdictions, challenging our patent rights. The legal threshold for initiating such proceedings may be low, so that even proceedings with a low probability of success might be initiated. An adverse determination in any such challenges may result in loss of exclusivity or in patent claims being narrowed, invalidated, or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products.

We are a biopharmaceutical company focused on developing and commercializing novel therapies for neurological disorders with significant unmet medical need. We have a diverse portfolio of product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are either no approved therapies treating the underlying disease or suboptimal treatment options. We were foundedincorporated in April 2016 and are led by a management team experienced in the development and commercialization of groundbreaking therapeutics.

Since inception, we have incurred significant losses and negative cash flows from operations. During the threesix months ended MarchJune 31,30, 2026 and 2025, we incurred net losses of $12.3$28.5 million and $14.0$16.1 million, respectively, and used $8.7$30.9 million and $12.7$21.6 million of cash in operations, respectively. As of MarchJune 31,30, 2026, we had an accumulated deficit of $301.5$317.7 million, and we do not expect positive cash flows from operations for the foreseeable future. We expect to continue to incur significant and increasing losses for the foreseeable future, and our net losses may fluctuate significantly from period to period, depending on the timing of expenditures on our planned research and development activities.

Since inception through the date of this filing, we have raised aggregate gross proceeds of $427.1$432.6 million, including $103.5 million from our initial public offering in October 2020, $116.0 million from the sale of our redeemable convertible preferred stock, $103.6$109.1 million from private placement financings,financings (including the August 2026 private placement), $69.0 million from the April 2026 underwritten public offering, $20.0 million from the issuance of debt, and $15.0 million upfront payment from Kaken Pharmaceutical Co., Ltd. received in April 2023. As of MarchJune 31,30, 2026, we had cash and cash equivalents of $54.1$96.3 million.

We believe that based on our current operating plan, our cash and cash equivalents of $54.1$96.3 million as of MarchJune 31,30, 2026 and the net proceeds from ourthe AprilAugust 2026 underwrittenprivate public offering of common stock and pre-funded warrantsplacement will be sufficient to fund our planned operations and debt obligations for at least 12 months following the issuance date of these financial statements included elsewhere in this Quarterly Report.

advance TA-ERT through aour planned TrAnsform confirmatory study in patients with MPS IIIB and expanded access programsprograms, both of which are expected to initiate in the fourth quarter of 2026 and are expected to enroll approximately 14 and 10 participants, respectively;

In November 2025, the U.S. Securities and Exchange Commission (“SEC”) declared effective a registration statement on Form S-3 (the “Shelf Registration”), covering the sale of up to $300.0 million of our securities. Also, in March 2026, we entered into an Open Market Sales AgreementSM (the “Sales Agreement”) with Jefferies LLC (“Jefferies”) pursuant to which we may elect to issue and sell, from time to time, shares of common stock having an aggregate offering price of up to $75.0 million under the Shelf Registration through Jefferies acting as the sales agent and/or principal. As of MarchJune 31,30, 2026, we have not issued any shares of common stock under the Sales Agreement.

Additionally, on April 22, 2026, we closed our previously announced underwritten public offering of 1,150,000 shares of our common stock at a public offering price of $50.00 per share and pre-funded warrants to purchase up to 50,000 shares of our common stock at a public offering price of $49.99 per pre-funded warrant (which equals the public offering price per share of common stock, less the $0.01 per share exercise price of each pre-funded warrant). In addition, we granted the underwriters a 30-day option to purchase up to 180,000 additional shares of common stock at the public offering price, less underwriting discounts and commissions, which was exercised in full. The grossnet proceeds to us from the offering, beforeafter deducting underwriting discounts and commissions and estimated offering expenses payable by us, were approximately $69.0$64.4 million.

The Avenue Loan Agreement makes available to us term loans in an aggregate principal amount of up to $50.0 million with (i) $15.0 million funded within 5 business days after the Avenue Closing Date (“Tranche 1”), (ii) up to $10.0 million to be made available to us between March 1, 2026 and September 30, 2026, subject to, among other things, our achievement of a key regulatory milestone related to our development of TA-ERT for the treatment of MPS IIIB (“Tranche 2”) and (iii) up to $15.0 million to be made available to us between September 1, 2026 and March 31, 2027, subject to, among other things, our achievement of an additional key regulatory milestone with respect to our development of TA-ERT for the treatment of MPS IIIB (“Tranche 3”). The Lender may make additional term loans of up to an additional $10.0 million (the “Discretionary Tranche 4” and collectively with Tranche 1, Tranche 2 and Tranche 3, the “Avenue Loans”), to be funded between October 1, 2027 and June 30, 2028, subject to, among other things, (i) our achievement of a certain commercial milestone and (ii) the mutual written agreement of us and the Lender (upon the Lender’s investment committee approval). The Avenue Loans bear interest at an annual rate equal to the greater of (x) the sum of 5.25% plus the prime rate as reported in The Wall Street Journal and (y) 12.25%. The Avenue Loans are secured by a lien on and security interest in all of our assets, including intellectual property, subject to agreed exceptions. The maturity date of the Avenue Loans is July 1, 2029 (the “Avenue Maturity Date”). The Avenue Loan Agreement does not contain any minimum cash requirement or other financial covenants. As of MarchJune 31,30, 2026, the outstanding principal was $15.0 million under Tranche 1.

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

Research and development expenses decreasedincreased by $3.3$12.6 million during the three months ended MarchJune 31,30, 2026 compared to the three months ended MarchJune 31,30, 2025. The decreaseincrease in clinical development expenses of $3.9$4.7 million was primarily related to lowerincreased acquisitionexpenses relatedfor costsTA-ERT of $5.7$5.8 million, offset by the discontinuation of the tildacerfont congenital adrenal hyperplasia (“CAH”) development program of $1.9 million, offset by increased expenses for TA-ERT of $3.7$1.1 million. The increase in manufacturing expenses of $1.1$7.4 million was primarily related to TA-ERT. There was also an increase in personnel related costs of $0.3 million.

General and administrative expenses increased by $0.8$1.2 million during the three months ended MarchJune 31,30, 2026 compared to the three months ended MarchJune 31,30, 2025 primarily due to an increase in professionalpersonnel feesrelated costs of $0.5$0.9 million and an increase in personnelprofessional related costsfees of $0.2 million.

Interest expense increased by $0.6$1.1 million during the three months ended MarchJune 31,30, 2026 compared to the three months ended MarchJune 31,30, 2025 and increased by $1.7 million during the six months ended June 30, 2026 compared to the six months ended June 30, 2025 due to an increase in our debt and its related interest rate and an increase in the related amortization of debt discount and issuance costs.

Interest and other income, net increased by $0.2$0.6 million during the three months ended MarchJune 31,30, 2026 compared to the three months ended MarchJune 31,30, 2025 and increased by $0.7 million during the six months ended June 30, 2026 compared to the six months ended June 30, 2025 primarily due to higher yield earned on money market fund balances.

Change in fair value of warrant and conversion option liabilities decreasedincreased by $0.2 million during the three months ended MarchJune 31,30, 2026 compared to the three months ended MarchJune 31,30, 2025 and decreased by $0.1 million during the six months ended June 30, 2026 compared to the six months ended June 30, 2025. In the prior period, the change in fair value was for pre-funded warrants issued to HBM Alpha Therapeutics, Inc. In the current period, the change in fair value relates to warrants and the conversion option under the Avenue Loan Agreement.

Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from operations. We anticipate that we will continue to incur net losses for the foreseeable future. As of MarchJune 31,30, 2026 and December 31, 2025, we had an accumulated deficit of $301.5$317.7 million and $289.2 million, respectively. As of MarchJune 31,30, 2026 and December 31, 2025, we had cash and cash equivalents of $54.1$96.3 million and $48.9 million, respectively.

Since inception through the date of this filing, we have raised aggregate gross proceeds of $427.1$432.6 million, including $103.5 million from our initial public offering in October 2020, $116.0 million from the sale of our redeemable convertible preferred stock, $103.6$109.1 million from private placement financings,financings (including the August 2026 private placement), $69.0 million from the April 2026 underwritten public offering, $20.0 million from the issuance of debt, and $15.0 million upfront payment from Kaken Pharmaceutical Co., Ltd. received in April 2023. As of MarchJune 31,30, 2026, we had cash and cash equivalents of $54.1$96.3 million. We believe that based on our current operating plan, our cash and cash equivalents of $54.1 million as of March 31, 2026 and the net proceeds from our April 2026 underwritten public offering of common stock and pre-funded warrants will be sufficient to fund our planned operations and debt obligations for at least 12 months following the issuance date of these financial statements included elsewhere in this Quarterly Report.

In November 2025, the SEC declared effective the Shelf Registration covering the sale of up to $300.0 million of our securities. Also, in March 2026, we entered into the Sales Agreement with Jefferies, pursuant to which we may elect to issue and sell, from time to time, shares of common stock having an aggregate offering price of up to $75.0 million under the Shelf Registration through Jefferies acting as the sales agent and/or principal (the “ATM Offering”). We have also filed a prospectus supplement with the SEC in connection with the ATM Offering under the Shelf Registration. Upon delivery of an issuance notice and subject to the terms and conditions of the Sales Agreement, Jefferies may sell the shares at market prices by any method deemed to be an “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act, including sales made directly on or through The Nasdaq GlobalCapital Select Market (“Nasdaq”),Market, the existing trading market for our common stock. As of MarchJune 31,30, 2026, we have not issued any shares of common stock pursuant to the Sales Agreement. We have agreed to pay Jefferies commissions for its services of acting as agent of 3.0% of the gross proceeds from the sale of the shares pursuant to the Sales Agreement. We have also agreed to provide Jefferies with customary indemnification and contribution rights.

As of MarchJune 31,30, 2026, future payments of principal and interest on the Avenue Loans, which matures in July 2029, were $20.4$19.9 million. For a description of the terms of the Avenue Loans, see the section titled “Material Agreements — Loan Agreement with Avenue” above.

As of MarchJune 31,30, 2026, the total undiscounted lease payments for our non-cancelable operating lease for office space, which terminates in February 2028 unless renewed, was $0.7$0.6 million.

We have also entered into license and collaboration agreements under which we are obligated to make aggregate milestone payments upon the achievement of specified milestones as well as royalty payments. As of MarchJune 31,30, 2026, we were unable to estimate the timing or likelihood of achieving these milestones or generating future product sales. For a description of the terms of our license and collaboration agreements, see Note 7 to our unaudited condensed financial statements “License Agreements” presented elsewhere in this Quarterly Report.

Net cash used in operating activities decreasedincreased by $4.0$9.3 million during the threesix months ended MarchJune 31,30, 2026 compared to the threesix months ended MarchJune 31,30, 2025 primarily due to lower payments driven by decreasedincreased clinical development activities andfor TA-ERT offset by the receipt of $2.6 million related to the Allievex Purchase Agreement due to the completed Allievex bankruptcy proceedings.

For the threesix months ended MarchJune 31,30, 2026, net cash used in investing activities was related to purchase of property and equipment.

For the threesix months ended MarchJune 31,30, 2026, net cash provided by financing activities was $13.9$78.4 million, consisting primarily of net proceeds from the issuance of common stock and warrants of $64.4 million and net proceeds from the Avenue Loans of $14.0 million.

For the threesix months ended MarchJune 31,30, 2025, net cash used in financing activities was $0.4$0.8 million, consisting primarily of principal payments on debt of $0.4$0.8 million.

Our critical accounting estimates are described in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Estimates” in the Annual Report. During the threesix months ended MarchJune 31,30, 2026, there were no changes to our critical accounting estimates from those discussed in the Annual Report.