Dyne Therapeutics, Inc. (DYN)

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations.

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our condensed consolidated financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q, or this Quarterly Report, and our audited consolidated financial statements and related notes for the year ended December 31, 2025, included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC, on March 2, 2026. Some of the information contained in this discussion and analysis or set forth elsewhere in this Quarterly Report, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this Quarterly Report, our actual results could differ materially from the results described in, or implied by, the forward-looking statements contained in the following discussion and analysis.

Overview

We are a clinical-stage company focused on delivering functional improvement for people living with genetically driven neuromuscular diseases. Our proprietary FORCE platform is designed to leverage the transferrin receptor 1, or TfR1, to deliver targeted therapeutics to muscle tissue and the central nervous system, or CNS. The FORCE platform utilizes an antigen-binding fragment antibody, or Fab, targeting TfR1 linked to a payload that we rationally design to target the genetic basis of the disease we are seeking to treat. With our FORCE platform, we have the flexibility to deploy different classes of payloads (such as oligonucleotides and enzymes) with specific mechanisms of action that modify target functions. We currently leverage this modularity to focus on neuromuscular diseases with high unmet need, with etiologic targets and with clear translational potential from preclinical disease models to well-defined clinical development and regulatory pathways.

Using our FORCE platform, we are assembling a broad portfolio of product candidates, including product candidates being developed for Duchenne muscular dystrophy, or DMD, myotonic dystrophy type 1, or DM1, facioscapulohumeral dystrophy, or FSHD, and Pompe disease. In addition, we plan to expand our portfolio through development efforts focused on diseases involving the CNS, rare skeletal muscle diseases, and cardiac and metabolic muscle diseases, including some with larger patient populations. We have identified product candidates for each of our DMD, DM1, FSHD and Pompe programs that are in varying stages of preclinical and clinical development.

DMD

We are developing zeleciment rostudirsen, or z-rostudirsen (also known as DYNE-251), for the treatment of DMD amenable to exon 51 skipping. Z-rostudirsen is designed to enable the production of near full-length dystrophin in muscle and the CNS to provide functional improvement. Z-rostudirsen has received Breakthrough Therapy, Fast Track and Rare Pediatric Disease designations from the U.S. Food and Drug Administration, or FDA, as well as Orphan Drug designation

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from the FDA, the European Medicines Agency and the Japanese Ministry of Health, Labour and Welfare for the treatment of individuals with DMD, amenable to exon 51 skipping. Additionally, we are advancing four development candidates (DYNE-253, DYNE-245, DYNE-244 and DYNE-255) for the treatment of DMD amenable to skipping of exons 53, 45, 44, 55, respectively, into IND-enabling studies.

Z-rostudirsen is being evaluated in the long-term extension portion of the DELIVER trial, a global Phase 1/2 clinical trial designed to be registrational, and the FORZETTO trial, a global Phase 3 clinical trial designed to be confirmatory. We have aligned with the FDA on the FORZETTO trial design and protocol. The registrational expansion cohort of the global Phase 1/2 DELIVER clinical trial of z-rostudirsen met its primary endpoint. Data from the DELIVER trial served as the basis for a biologics license application, or BLA, for potential U.S. Accelerated Approval.

In May 2026, we initiated our Phase 3 FORZETTO clinical trial, a global, randomized, placebo-controlled, double-blind, confirmatory Phase 3 trial designed to assess the efficacy, safety, and tolerability of z-rostudirsen administered intravenously to ambulatory male participants with DMD amenable to exon 51 skipping. The trial will enroll approximately 90 participants 4 to 18 years of age who will be randomized 1:1 to receive 20 mg/kg of z-rostudirsen or placebo every four weeks (Q4W). The primary endpoint is the change from baseline in rise from floor (RFF) velocity at Week 73. Secondary endpoints include changes from baseline in stride velocity 95th centile (SV95C), North Star Ambulatory Assessment (NSAA) total score, 10-meter walk/run (10MWR) velocity, four-stair climb (4SC) velocity and forced vital capacity percent predicted (FVC%p), as well as additional functional and patient-reported outcome measures. Following the 72-week double-blind placebo-controlled treatment period, participants will be eligible to enroll in a 96-week open-label long-term extension. We have aligned with the FDA on the FORZETTO Phase 3 trial design and protocol. FORZETTO is intended to serve as a confirmatory trial to support the potential conversion of Accelerated Approval to traditional approval in the United States and to support ex-U.S. marketing applications.

In July 2026, we announced that the FDA accepted for review our BLA for z-rostudirsen for the treatment of individuals with DMD amenable to exon 51 skipping. The FDA has granted the BLA priority review and assigned a Prescription Drug User Fee Act, or PDUFA, target action date of January 21, 2027. We continue to expect a potential U.S. launch of z-rostudirsen in the first quarter of 2027, assuming FDA approval is received on the anticipated timeline. We continue to pursue approval pathways outside of the United States for z-rostudirsen.

DM1

We are developing zeleciment basivarsen, or z-basivarsen (also known as DYNE-101), for the treatment of DM1. Z-basivarsen is designed to deliver functional improvement in individuals living with DM1 by reducing toxic nuclear DMPK RNA to release splicing proteins and allow normal mRNA processing. Z-basivarsen has been granted Breakthrough Therapy, Orphan Drug and Fast Track designations by the FDA and Orphan Drug designation by the European Medicines Agency and the Japanese Ministry of Health, Labour and Welfare for the treatment of DM1.

Z-basivarsen is being evaluated in the ACHIEVE trial, a global Phase 1/2 clinical trial designed to be registrational, and the HARMONIA trial, a global Phase 3 clinical trial designed to be confirmatory. We have aligned with the FDA on the HARMONIA trial design and protocol.

In March 2026, we initiated our Phase 3 HARMONIA clinical trial, a global, randomized, placebo controlled, double-blind, confirmatory Phase 3 trial designed to assess the multi-system efficacy, safety, and tolerability of z-basivarsen administered intravenously to individuals with DM1. We began dosing patients in July 2026. The trial will enroll approximately 150 participants age 16 and older who will be randomized 1:1 to receive 6.8 mg/kg of z-basivarsen or placebo every eight weeks (Q8W). The primary endpoint is the change from baseline in the five times sit to stand (5xSTS) test at week 49. Secondary endpoints include video hand opening time, quantitative muscle testing, the 10-Meter Walk/Run test, the Myotonic Dystrophy Health Index, and additional patient- and clinician-reported outcomes. The trial also includes a broad set of exploratory endpoints designed to assess multiple domains of DM1 CNS impact. Following the 48-week double-blind placebo-controlled treatment period, patients will be eligible to enroll in a 24-week long-term extension.

In June 2026, we completed enrollment of 71 participants in the registrational expansion cohort, or REC, of the ACHIEVE trial. We plan to announce data from the REC in the first quarter of 2027 to support a potential BLA submission to the FDA for U.S. Accelerated Approval in the third quarter of 2027. We anticipate a potential U.S. launch of z-basivarsen in the first half of 2028, assuming we receive favorable data from the REC, priority review is granted, and FDA approval is received on the anticipated timeline. We continue to pursue approval pathways outside of the United States for z-basivarsen.

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FSHD

We are developing DYNE-302 for the treatment of FSHD. DYNE-302 is designed to deliver functional improvement in individuals living with FSHD by reducing aberrant DUX4 expression. We are progressing DYNE-302 toward clinical development.

In June 2024 and June 2025, we announced preclinical data for DYNE-302, our product candidate for FSHD, that demonstrated robust and durable DUX4 suppression and functional benefit in a mouse model. We generated these data using an innovative hTfR1/iFLExD mouse model we developed that expresses TfR1 and enables tunable DUX4 induction in skeletal muscle. In hTfR1/iFLExD mice, a single intravenous dose of DYNE-302 resulted in dose-dependent and robust reduction of the DUX4 transcriptome that lasted up to three months, with benefit on muscle structure. DYNE-302 also demonstrated prevention and reversal of muscle weakness.

In July 2026, we announced that we received clearance from the FDA for our investigational new drug, or IND, application to initiate a Phase 1 clinical trial for DYNE-302 in FSHD. DYNE-302 leverages the same FORCE platform as our first two clinical programs, z-rostudirsen in DMD amenable to exon 51 skipping and z-basivarsen in DM1. We plan to evaluate DYNE-302 in a Phase 1 randomized, placebo-controlled, double-blind, multiple ascending dose clinical trial in ambulatory adult individuals with FSHD with a primary endpoint of safety and tolerability. The trial will also assess pharmacokinetics and pharmacodynamics, including change from baseline in muscle DUX4 transcriptome and plasma KHDC1L levels.

In the first cohort, nine participants will receive three intravenous doses administered every four weeks (Q4W), randomized 2:1 to DYNE-302 1.5 mg/kg (approximate siRNA dose) or placebo. Following the completion of this cohort, we intend to evaluate higher dosing and less frequent administration. Participants who complete the placebo-controlled period may enter an open-label long-term extension and receive DYNE-302 for up to an additional 96 weeks. We intend to pursue a traditional approval pathway in the U.S. for DYNE-302.

Pompe

We are developing DYNE-401 for the treatment of Pompe disease. DYNE-401 is designed to deliver an enzyme replacement therapy to address the deficiency of the lysosomal enzyme, GAA, that causes Pompe disease. We engineered DYNE-401 by leveraging the FORCE platform to deliver GAA. We evaluated GAA delivery with our FORCE platform in vivo using hTfR1/6Neo mice, that were developed by crossing the well-established 6Neo mouse model of Pompe with mice expressing human transferrin receptor 1. Using this approach, intravenous administration cleared glycogen in muscle and the CNS and normalized lysosomal size in hTfR1/6Neo mice. This approach reduced serum neurofilament light chain, a biomarker of axonal injury, providing evidence of benefit in the CNS and displayed superior dose potency compared to GAA alone. Additional data with this approach supported the potential for monthly dosing, which is less frequent than approved enzyme replacement therapies for Pompe.

Pipeline expansion

We continue to explore additional applications for our proprietary FORCE platform, along with further iterations. To that end, we have identified two compounds, which we refer to as Conjugate 1 and Conjugate 2, utilizing a Fab conjugated to micr

[Excerpt truncated for page length; source filing is linked above.]

Overview

We are a clinical-stage company focused on delivering functional improvement for people living with genetically driven neuromuscular diseases. Our proprietary FORCE platform is designed to leverage the transferrin receptor 1, or TfR1, to deliver targeted therapeutics to muscle tissue and the central nervous system, or CNS. The FORCE platform utilizes an antigen-binding fragment antibody, or Fab, targeting TfR1 conjugated to a payload that we rationally design to target the genetic basis of the disease we are seeking to treat. With our FORCE platform, we have the flexibility to deploy different classes of payloads (such as oligonucleotides and enzymes) with specific mechanisms of action that modify target functions. We currently leverage this modularity to focus on neuromuscular diseases with high unmet need, with etiologic targets and with clear translational potential from preclinical disease models to well-defined clinical development and regulatory pathways.

Using our FORCE platform, we are assembling a broad portfolio of product candidates, including product candidates being developed for Duchenne muscular dystrophy, or DMD, myotonic dystrophy type 1, or DM1, facioscapulohumeral dystrophy, or FSHD, and Pompe disease. In addition, we plan to expand our portfolio through development efforts focused on diseases involving the CNS, rare skeletal muscle diseases, and cardiac and metabolic muscle diseases, including some with larger patient populations. We have identified product candidates for each of our DMD, DM1, FSHD and Pompe programs that are in varying stages of preclinical and clinical development.

DMD

We are developing zeleciment rostudirsen, or z-rostudirsen (also known as DYNE-251), for the treatment of exon 51 skip amenable DMD. Z-rostudirsen is designed to enable the production of near full-length dystrophin in muscle and the CNS to provide functional improvement. Z-rostudirsen has received Breakthrough Therapy, Fast Track and Rare Pediatric Disease designations from the U.S. Food and Drug Administration, or FDA, as well as Orphan Drug designation from the FDA, the European Medicines Agency and the Japanese Ministry of Health, Labour and Welfare for the treatment of individuals with DMD, amenable to exon 51 skipping. Additionally, we are advancing four development candidates (DYNE-253, DYNE-245, DYNE-244 and DYNE-255) for the treatment of DMD amenable to skipping of exons 53, 45, 44, 55, respectively, into IND-enabling studies.

Z-rostudirsen is currently being evaluated in the DELIVER trial, a global Phase 1/2 clinical trial which is designed to be registrational. We plan to submit a biologics license application, or BLA, to the FDA for U.S. Accelerated Approval in the second quarter of 2026 based on dystrophin as a surrogate endpoint. We continue to expect a potential U.S. launch of z-rostudirsen in the first quarter of 2027, assuming FDA grants priority review and FDA approval is received on the anticipated timeline. Further, we plan to initiate a global confirmatory Phase 3 clinical trial of z-rostudirsen in the second quarter of 2026, and we have aligned with the FDA on the Phase 3 trial design and protocol. We continue to pursue approval pathways outside of the United States for z-rostudirsen.

DM1

We are developing zeleciment basivarsen, or z-basivarsen (also known as DYNE-101), for the treatment of DM1. Z-basivarsen is designed to deliver functional improvement in individuals living with DM1 by

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reducing toxic nuclear DMPK RNA to release splicing proteins and allow normal mRNA processing. Z-basivarsen has been granted Breakthrough Therapy, Orphan Drug and Fast Track designations by the FDA and Orphan Drug designation by the European Medicines Agency and the Japanese Ministry of Health, Labour and Welfare for the treatment of DM1.

Z-basivarsen is being evaluated in the ACHIEVE trial, a global Phase 1/2 clinical trial which is designed to be registrational. We anticipate a potential U.S. launch of z-basivarsen in the first quarter of 2028, assuming we receive favorable data, priority review is granted, and FDA approval is received on the anticipated timeline. We plan to initiate a Phase 3 clinical trial of z-basivarsen in March 2026, and we have aligned with the FDA on the Phase 3 trial design and protocol. We continue to pursue approval pathways outside of the United States for z-basivarsen.

FSHD

We are developing DYNE-302 for the treatment of FSHD. DYNE-302 is designed to deliver functional improvement in individuals living with FSHD by reducing aberrant DUX4 expression. We are progressing DYNE-302 toward clinical development.

In June 2024 and June 2025, we announced preclinical data for DYNE-302, our product candidate for FSHD, that demonstrated robust and durable DUX4 suppression and functional benefit in a mouse model. We generated these data using an innovative hTfR1/iFLExD mouse model we developed that expresses TfR1 and enables tunable DUX4 induction in skeletal muscle. In hTfR1/iFLExD mice, a single intravenous dose of DYNE-302 resulted in dose-dependent and robust reduction of the DUX4 transcriptome that lasted up to three months, with benefit on muscle structure. DYNE-302 also demonstrated prevention as well as reversal of muscle weakness.

Pompe

We are developing a product candidate, DYNE-401, to deliver an enzyme replacement therapy to address the deficiency of the lysosomal enzyme, GAA, that causes Pompe disease. We engineered FORCE-GAA by leveraging the FORCE platform and evaluated efficacy in vivo using hTfR1/6Neo mice, that were developed by crossing the well-established 6Neo mouse model of Pompe with mice expressing human transferrin receptor 1. Using this approach, intravenous administration cleared glycogen in muscle and the CNS and normalized lysosomal size in hTfR1/6Neo mice. This approach reduced serum neurofilament light chain, a biomarker of axonal injury, providing evidence of benefit in the CNS and displayed superior dose potency compared to GAA alone. Additional data with this approach supported the potential for monthly dosing which is less frequent than approved enzyme replacement therapies for Pompe.

We were incorporated and commenced operations in 2017. Since our incorporation, we have devoted substantially all of our financial resources and efforts to organizing and staffing our company, business planning, raising capital, conducting research and development activities and filing and prosecuting patent applications. We do not have any products for sale and have not generated any revenue from product sales or otherwise. To date, we have principally raised capital through sales of equity securities and our borrowing under our Loan and Security Agreement, or the Loan Agreement, with Hercules Capital, Inc., or Hercules.

Since our inception, we have incurred significant operating losses. Our ability to generate any product revenue or product revenue sufficient to achieve profitability will depend on the successful development and eventual commercialization of one or more product candidates. For the years ended December 31, 2025, 2024 and 2023, we reported net losses of $446.2 million, $317.4 million and $235.9 million, respectively. As of December 31, 2025, we had an accumulated deficit of $1.4 billion.

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We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future. We expect that our expenses and capital expenditure requirements will increase substantially in connection with our ongoing activities, particularly if and as we:

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advance our product candidates for DMD, DM1, FSHD and Pompe and conduct research programs in additional indications;

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expand the capabilities of our proprietary FORCE platform;

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seek marketing approvals for any product candidates that successfully complete clinical trials;

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obtain, expand, maintain, defend and enforce our intellectual property portfolio;

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hire additional clinical, regulatory and scientific personnel;

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establish manufacturing sources for any product candidate we may develop, including the Fab antibody, linkers and therapeutic payload that will comprise the product candidate, and secure supply chain capacity to provide sufficient quantities for preclinical and clinical development and commercial supply;

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ultimately establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval; and

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add operational, legal, compliance, financial and management information systems and personnel to support our research, product development and future commercialization efforts, as well as to support our operations as a public company.

We will not generate revenue from product sales unless and until we successfully complete clinical development and obtain regulatory approval for any product candidates we may develop. If we obtain regulatory approval for or otherwise commercialize any product candidates we may develop, we expect to incur significant expenses related to developing our commercialization capabilities to support product sales, marketing and distribution. Further, we expect to continue to incur additional costs associated with operating as a public company.

As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and licensing arrangements, and terms loans under our Loan Agreement with Hercules. We may be unable to raise additional funds or enter into such other agreements or arrangements when needed, on favorable terms, or at all. If we fail to raise capital or enter into such agreements or arrangements as and when needed, we may have to significantly delay, reduce or eliminate the development or future commercialization of one or more product candidates we may develop.

Because of the numerous risks and uncertainties associated with product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to raise capital, maintain our research and development efforts, expand our business or continue our operations at planned levels, and as a result we may be forced to substantially reduce or terminate our operations.

We believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses, debt service obligations and capital expenditure requirements into the first quarter of 2028.

We have based our estimate as to how long we expect we will be able to fund our operations, debt service obligations and capital expenditure requirements on assumptions that may prove to be wrong. We could use our available capital resources sooner than we currently expect, in which case we would be

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required to obtain additional financing, which may not be available to us on acceptable terms, or at all. Our failure to raise capital as and when needed would have a negative impact on our financial condition and our ability to pursue our business strategy. See “—Liquidity and capital resources” below. These estimates do not give effect to any additional funding tranches we may obtain access to under our Loan Agreement with Hercules, subject to the achievement of specified clinical, regulatory and commercial milestones, and do not give effect to any revenue we may generate on commercial sales of any products for which we obtain regulatory approval.

Impact of Tariffs

The U.S. administration has announ

[Excerpt truncated for page length; the complete text is on the linked full-MD&A page.]