NASDAQ: MAZE

Our second program, MZE782, is an oral, small molecule inhibitor for the treatment of patients with phenylketonuria, or PKU, an inherited metabolic disorder, and CKD. In September 2025, we reported results from our Phase 1 clinical trial of MZE782, in which we enrolled 112 healthy adult volunteers. MZE782 was well tolerated across all doses in all cohorts and demonstrated a favorable PK profile after single and multiple oral doses. MZE782 produced dose-dependent increases in 24-hour urinary excretion of the neutral amino acids phenylalanine, or Phe, and glutamine, or Gln, across both single ascending dose, or SAD, and multiple ascending dose, or MAD, cohorts, confirming target engagement and SLC6A19 inhibition. We also observed dose-dependent changes in estimated glomerular filtration rate, or eGFR, in healthy individuals with MZE782, similar to those seen with SGLT2 inhibitors, suggesting a potential beneficial effect on kidney physiology. We plan to initiate two Phase 2 proof-of-concept trials of MZE782 in 2026 in patients with PKU and patients with CKD.

Our Compass platform supports end-to-end variant identification and functionalization capabilities as well as advanced research tools and methodologies for drug discovery and development. In addition to our clinical programs, we are advancing multiple programs in preclinical development. We also have partnered other programs discovered through our Compass platform with leading pharmaceutical and biotechnology companies who are now developing those programs.

Pipeline

Our pipeline consists of small molecule product candidates focused on kidney and metabolic diseases. Our most advanced program, MZE829, is in Phase 2 clinical development for AMKD. MZE782 is Phase 2 ready for PKU and CKD. In addition, we have research and discovery programs targeting kidney and metabolic diseases. We also have a partnered program, MZE001 (S606001), for Pompe disease, which we licensed to Shionogi & Co., Ltd and is in Phase 2 development.

4

Figure 1: Pipeline

Strategy

We leverage our Compass platform to discover and develop precision medicines in subsets of diseases to achieve improved treatment outcomes for patients. Our focus on kidney and metabolic diseases is driven in part by the emerging understanding of the interconnectivity of these diseases. We actively explore expanding development to other patient populations based on emerging genetic data and unmet medical need.

•
Advance MZE829 program in AMKD: We intend to advance the clinical development of MZE829 for the treatment of AMKD, a disease with significant unmet medical need.

•
Advance MZE782 program in PKU and CKD: We intend to advance the clinical development of MZE782 for the treatment of PKU and CKD, each representing patient populations with significant unmet medical need.

•
Commercialization: We intend to maximize the commercial potential of our pipeline by advancing MZE829 and MZE782 through commercialization in geographies where we believe we can effectively commercialize independently, including through the development of targeted capabilities to support adoption.

•
Compass Platform: We intend to leverage our proprietary Compass platform to expand our precision medicine pipeline by identifying and prioritizing novel drug targets in subsets of kidney and metabolic diseases with significant unmet need. The Compass platform is designed to integrate genetic insights to identify well-validated targets and discover therapeutic agents intended to (i) mimic protective genetic variants, (ii) correct the effects of toxic genetic variants, or (iii) target genetic modifiers.

Clinical programs

MZE829 – APOL1-Mediated Kidney Disease (AMKD)

Indication and Unmet Need

Our most advanced program, MZE829, is an oral, small molecule inhibitor of APOL1 in development for the treatment of AMKD. AMKD is a serious, life-threatening, genetically driven form of CKD associated with high-risk coding variants in both alleles of the APOL1 gene.

These variants are most prevalent in individuals of West African ancestry, including many who identify as Black, African American, Afro-Caribbean, and Latina/Latino. The high-risk APOL1 variants are believed to have evolved due to their protective effect against Human African trypanosomiasis, or HAT, also known as sleeping sickness, a parasitic infection endemic to parts of sub-Saharan Africa that is typically fatal if untreated.

5

Individuals who inherit two high-risk APOL1 variants have a substantially increased risk of developing CKD, frequently experience earlier onset of kidney dysfunction, often before age 50, and are at increased risk of accelerated disease progression. They may initiate dialysis approximately ten years earlier than other CKD populations. Despite treatment with currently available standard of care, including renin-angiotensin-aldosterone system inhibitors and other supportive therapies, clinical outcomes in AMKD remain suboptimal. Many patients continue to experience rapid decline in renal function and progress to end-stage kidney disease, or ESKD. Once patients reach ESKD, they require chronic dialysis or kidney transplantation, both of which are associated with significant morbidity, mortality, reduced quality of life, and substantial healthcare costs.

AMKD affects a broad population across multiple underlying CKD diagnoses. In the United States, approximately six million, or 13%, of African Americans are estimated to carry two high-risk APOL1 variants and are therefore at elevated risk of developing AMKD. It is further estimated that approximately 20% of these individuals, representing over one million people, have CKD attributable, at least in part, to AMKD. We estimate that at least 250,000 patients in the United States represent an initial, addressable broad AMKD population that may be responsive to targeted APOL1 inhibition based on disease stage and clinical characteristics.

AMKD spans diverse CKD subpopulations, including hypertensive non-diabetic CKD, diabetic kidney disease, focal segmental glomerulosclerosis, or FSGS, and other etiologies such as systemic lupus erythematosus, or SLE, HIV-associated nephropathy, or HIVAN, and sickle cell nephropathy. Hypertensive non-diabetic and diabetic patients with APOL1 high-risk variants together represent the majority of the AMKD population. Across these conditions, the presence of APOL1 high-risk genotypes is associated with increased susceptibility to kidney injury and more rapid progression of disease.

Despite the prevalence, severity, and genetic basis of AMKD, there are currently no approved therapies specifically indicated to treat AMKD. Existing treatments focus on management of blood pressure, glycemic control, and other downstream contributors to CKD progression, but they do not directly target APOL1-driven pathogenic mechanisms. As a result, a significant unmet medical need remains for therapies that address the underlying biology of AMKD and have the potential to meaningfully delay disease progression and reduce the risk of ESKD.

Mechanism of Action

APOL1 is a channel-forming innate immunity protein found in circulating high-density lipoproteins in humans and certain primates. In addition to circulating forms, APOL1 is also found locally in kidney endothelial cells and podocytes. Circulating APOL1 mediates resistance to infection from the parasite Trypanosoma brucei through a lytic pore formation mechanism, whereas the function of the cellular forms of APOL1 are less well understood.

The G1 and G2 variants of APOL1 evolved in response to parasites that became resistant to normal APOL1. However, individuals with two copies of the G1 and/or G2 variants have been found to be at higher risk for developing CKD and progressing to ESKD. Rare individuals lacking APOL1 altogether appear to have no higher risk of developing CKD than the general population, suggesting that AMKD is the result of toxicity associated with the risk variants rather than simple loss of APOL1 function. This observation supports the therapeutic hypothesis that selective inhibition of APOL1 activity may reduce the risk and progression of AMKD. It also provides genetic support for the safety of maximally inhibiting APOL1.

APOL1 risk variants are believed to contribute to kidney injury through increased pore formation and ion conductance in podocytes, specialized epithelial cells in the glomerulus that are essential to maintaining the kidney’s filtration barrier. Increased numbers of APOL1 pores disrupt podocyte function and are associated with dysregulated ion flux, including sodium, potassium, calcium, and hydrogen ions. Disruption of cellular ion homeostasis may lead to podocyte dysfunction and cell death, contributing to progressive kidney damage.

APOL1 protein is dynamically regulated within cells and undergoes ongoing synthesis and turnover. As a result, new APOL1 monomers may continually assemble into pores. In addition, inflammatory stimuli are thought to increase its expression. As a result, new APOL1 monomers may continually assemble into additional pores over time, and this may occur to a greater extent with acute or chronic inflammation. We believe that inhibition of pore function alone may not fully address this ongoing biology.

Although the link between APOL1 variants and renal dysfunction has been known for over a decade, we identified a protective variant, N264K, that underpins our therapeutic approach for MZE829. When present, this variant has been shown to reduce the conductance of ions through the APOL1 pore, thereby suppressing the toxicity of APOL1 in kidney cells. In a cross-sectional analysis of approximately 121,000 participants of African ancestry from the Million Veteran Program, the presence of N264K was associated with a statistically significant reduction (p < 0.001) in risk of CKD and ESKD among carriers of two APOL1 risk variants. These findings were replicated in independent cohorts, including Vanderbilt University Medical Center’s BioVU and the National Institutes of Health All of Us research program. A meta-analysis across cohorts demonstrated a 57% reduced risk of CKD and an 81% reduced risk of ESKD in APOL1 high-risk individuals carrying the N264K protective variant.

6

In human kidney cell models, introduction of the N264K mutation blocked APOL1 ion conductance and reduced toxicity associated with the G2 risk variant. These data informed our therapeutic hypothesis that therapeutic inhibition of APOL1 pore function may mitigate APOL1-mediated kidney injury.

Based on these observations that the kidney pathology in AMKD results from both abnormal pore function and increased pore expression, we believe that targeting both pore formation and pore function may provide more comprehensive modulation of APOL1-mediated toxicity by reducing the creation of new pores while simultaneously limiting ion conductance through existing pores.

MZE829 is our development candidate designed to phenocopy the protective effects observed with the N264K variant. Preclinical studies suggest that MZE829 may disrupt APOL1 pore assembly in addition to inhibiting pore function, a so-called dual mechanism. By interfering with pore formation, MZE829 is designed to reduce the formation of new APOL1 pores. By inhibiting ion conductance through formed pores, MZE829 is designed to limit dysregulated ion flux associated with the high-risk APOL1 variants.

Clinical summary

We completed a Phase 1 randomized, placebo-controlled, single and multiple ascending dose clinical trial evaluating MZE829 in 111 healthy adult volunteers. The primary objective of the Phase 1 trial was to assess the safety and tolerability of single and multiple doses of MZE829 in healthy adult volunteers. The secondary objectives were to evaluate the food effect of a single dose of MZE829 and the pharmacokinetics of single and multiple doses of MZE829. As a part of the Phase 1 trial, we also investigated potential drug-drug interactions, or DDIs, to guide the use of concomitant, standard-of-care medicines in Phase 2.

In October 2024, we reported results from our Phase 1 trial in healthy volunteers. MZE829 was well tolerated at single doses up to 480 mg and multiple doses up to 350 mg daily for seven days. At likely therapeutic dosing levels, all treatment-related adverse events were reported as mild and self-limited without intervention. The most commonly reported treatment-related adverse event was headache. No serious or severe adverse events were reported at any dose. At the supratherapeutic dose of 480 mg, we observed mild and moderate treatment-related adverse events consisting of headache, nausea, vomiting and diarrhea. Due to the tolerability issues reported for multiple patients, we stopped dosing at the 480 mg QD level after two doses.

Dose-proportional PK was observed with low variability (10-40%) across doses and minimal urinary excretion (<1%). The observed half-life of MZE829 was approximately 15 hours, which supports the potential for MZE829 to be dosed once daily. Additionally, no clinically significant DDIs were identified, which we believe supports the ability for MZE829 to be administered together with standard-of-care medicines frequently used in patients with AMKD, including cyclosporine, tacrolimus and mycophenolate mofetil.

The results from our Phase 1 trial demonstrated that MZE829 was well tolerated and established the dosing regimen that we are taking into our Phase 2 trial in patients with AMKD. Patients with the high risk APOL1 genotype and proteinuric kidney disease are currently being enrolled into our Phase 2 trial to reflect a broad spectrum of AMKD patients. A dose of 250 mg orally administered once daily was chosen based on 13-week Good Laboratory Practice (GLP) toxicology studies performed in two species, and clinical safety, tolerability, and PK observed in Phase 1 that predicted that the associated exposure would exceed EC90 based on translational PK/PD (pharmacokinetic/pharmacodynamic) models of proteinuria in bacterial artificial chromosome, or BAC, transgenic mice expressing the human, high risk APOL1 genotype (see Figure 2 below).

7

Figure 2: MZE829 dose selection for Phase 2 based on BAC-transgenic human APOL1 G2/G2 mouse model of proteinuria. The exposure (steady state free plasma AUC0-24hr) – response (urinary albumin-to-creatinine ratio; uACR) curve from one of several mouse models is shown, overlayed with the exposures achieved in Phase 1 in healthy volunteers at 60, 120 and 240 mg once daily at steady state. Effective concentrations (EC) to achieve 30% (EC30), 60% (EC60) and 90% (EC90) reduction in proteinuria are shown. Similar models of chronic proteinuria on G1/G2 or G2/G2 backgrounds showed similar results.

Our Phase 2 clinical trial is an ongoing 12-week, open-label basket trial designed to evaluate the safety, efficacy and tolerability of MZE829 in adults with proteinuric CKD who have the APOL1 high-risk genotype. The initial two cohorts are enrolling participants aged 18 to 68 with CKD and urine albumin-to-creatinine ratio, or uACR, ≥300 mg, who carry the APOL1 high-risk genotype (G1/G1, G2/G2, G1/G2), meet eGFR criteria of at least 25 mL/min/1.73m2, and have received stable doses of current standard of care treatment for CKD for approximately eight weeks prior to screening. One cohort is comprised of participants with CKD and concurrent type 2 diabetes. The second cohort is comprised of participants with CKD diagnoses attributed to 1) hypertension or 2) FSGS and without a known cause for CKD other than APOL1. These first two cohorts are intended to include patients with a wide array of characteristics of CKD, including patients with more severe disease who have nephrotic range proteinuria and patients with more moderate disease who have lower levels of proteinuria. We further expect to expand into a third cohort of patients with FSGS.

A once daily oral dose of 250 mg MZE829 is being administered to participants in both cohorts over a 12-week treatment period, which we expect to be in an efficacious dose range based on translational in vivo pharmacology models such as the one shown above. The dose of 250 mg orally administered once daily is supported by the safety, tolerability, and PK profile observed in the Phase 1 trial and completed 13-week nonclinical toxicology studies.

The primary endpoint is safety and tolerability, with secondary endpoints including percent participants with at least 30% reduction from baseline in uACR at week 12 and plasma PK. Exploratory endpoints include change from baseline in urinary protein-to-creatinine ratio, or uPCR, at week 12. uACR is a sensitive measure of proteinuria in earlier stages of glomerular kidney disease, particularly in hypertension and diabetes, and has been used to assess risk of cardiovascular, or CV, disease.

In March 2026, we announced positive topline results from our Phase 2 trial of MZE829 in patients with AMKD. The open-label study enrolled 15 patients, all of whom were included in a safety and tolerability analysis, and 12 of whom were evaluable for efficacy based on meeting the per protocol compliance threshold. Patients were largely sub-nephrotic at baseline, with 10 patients having a baseline uACR of 300 to 1,000 mg/g. Across all enrolled patients, eight were diagnosed with AMKD without diabetes, of whom five patients had biopsy-confirmed FSGS, and seven were diagnosed with AMKD with diabetes.

MZE829 was generally well tolerated, with no serious adverse events or severe treatment-related adverse events reported. The most common treatment-related adverse events were headache and diarrhea (each reported in two patients), and one patient discontinued treatment due to mild nausea.

8

Treatment with MZE829 resulted in a mean reduction in uACR of 35.6% at week 12 in evaluable patients with broad AMKD, with 50% of such patients achieving at least a 30% reduction in uACR. In a subset of patients with FSGS, mean uACR reduction was 61.8%. Treatment of non-diabetic AMKD patients with MZE829 led to a clinically meaningful mean reduction from baseline uACR of 48.6%. Data were also observed in patients with AMKD with diabetes, with two of five evaluable patients achieving at least a 30% reduction in uACR (see Figure 3 below).

Figure 3: Change in proteinuria at week 12 in AMKD patients with and without diabetes.

We plan to continue enrollment in the Phase 2 trial and to advance MZE829 into a pivotal development program.

MZE782 – Phenylketonuria (PKU)

Indication and Unmet Need

Our second program consists of MZE782 as an investigational oral therapy in development for the treatment of PKU. PKU is an inherited metabolic disorder caused by mutations in the phenylalanine hydroxylase gene, resulting in deficiency of the enzyme responsible for metabolizing Phe. As a result, Phe is insufficiently metabolized and toxic levels accumulate in the body.

PKU is a lifelong genetic disease diagnosed at birth through routine neonatal screening. The disease exists across a spectrum ranging from mild to severe forms. Accumulation of Phe in blood and tissues can cause neurological symptoms including intellectual disability, behavioral abnormalities, seizures, and neuropsychological complications. If left untreated, elevated Phe levels may result in progressive and severe neurological impairment. Even in treated patients, fluctuating Phe levels may impair cognitive function and contribute to ongoing neuropsychiatric burden.

It is estimated that at least 60,000 individuals are living with PKU across key geographies. Current management of PKU includes adherence to a strict, lifelong low-phenylalanine diet, dietary supplementation with other essential amino acids, and frequent monitoring of plasma Phe levels. Maintaining dietary control is challenging and is associated with significant burden on patients and caregivers and major impact on quality-of-life.

Approved pharmacologic therapies include phenylalanine hydroxylase activators and enzyme substitution therapy; however, these treatments have major limitations. Phenylalanine hydroxylase activators enhance residual enzyme activity but are effective only in a subset of patients. Response rates vary depending on disease severity and genotype, and only an estimated 10% to 20% of patients with classic PKU respond to such treatment. Enzyme substitution therapy can reduce plasma Phe levels in a majority of treated adult patients; however, its use is associated with risks including anaphylaxis and injection site reactions and requires chronic subcutaneous administration.

Despite these therapies, many patients remain inadequately controlled, are intolerant to available treatments, or rely on medical diet alone. As a result, a substantial portion of the PKU population continues to experience persistent disease burden.

9

MZE782 is being developed as an oral therapy intended to address persistent gaps in PKU management. Based on its mechanism of action, MZE782 may address a broad PKU population, including patients with classic, moderate, and mild forms of disease.

An oral therapeutic approach may provide an alternative to injectable enzyme substitution therapy and may offer an additional treatment option for patients who are not adequately controlled on currently available therapies. In addition, improved control of plasma Phe levels, if demonstrated in clinical studies, may reduce reliance on strict dietary restriction. The clinical impact of MZE782 on Phe control and dietary management will be evaluated in future studies.

Mechanism of Action

MZE782 encodes the sodium-dependent neutral amino acid transporter BoAT1, which mediates absorption of neutral amino acids across the small intestine and reabsorption in the renal proximal tubule. As described above, we identified SLC6A19 as a therapeutic target through human genetic analyses demonstrating that reduced transporter activity is associated with favorable clinical phenotypes.

Phe is a neutral amino acid transported by SLC6A19. Accordingly, SLC6A19 plays a role in both intestinal uptake of dietary Phe and renal reabsorption of filtered Phe back into the bloodstream.

PKU is characterized by reduced activity of phenylalanine hydroxylase, resulting in impaired metabolism of Phe and accumulation of toxic levels in the blood and tissues. MZE782 is designed as an oral small molecule inhibitor of SLC6A19 and represents a substrate reduction approach intended to lower systemic Phe exposure.

By inhibiting SLC6A19 in the small intestine, MZE782 is intended to reduce absorption of dietary Phe. Inhibition of SLC6A19 in the kidney is intended to reduce reabsorption of filtered Phe and increase urinary excretion. Through these complementary mechanisms, SLC6A19 inhibition may reduce circulating Phe levels independent of phenylalanine hydroxylase activity. Because this mechanism does not rely on enhancing residual phenylalanine hydroxylase function, SLC6A19 inhibition may be applicable across the PKU spectrum, including patients with classic, moderate, and mild forms of disease, and may provide an option for patients who do not respond adequately to phenylalanine hydroxylase activators.

Clinical development status

In September 2025, we reported results from our Phase 1 clinical trial of MZE782 in which we enrolled 112 healthy adult volunteers who received a single dose of MZE782 ranging from 30 mg to 960 mg or multiple doses of MZE782 ranging from 120 mg to 240 administered once or twice daily. Treatment was well tolerated, with no serious adverse events, no severe adverse events and no treatment-related adverse events leading to discontinuation.

Dose-proportional PK was observed across doses with minimal urinary excretion (<1%). The observed half-life of MZE829 was approximately 11 hours. Exposure increased proportionally with dose, and steady-state was achieved by Day 3. This is supportive of a once- or twice-daily dosing regimen to be evaluated in Phase 2.

Pharmacodynamic assessments demonstrated dose-dependent increases in 24-hour urinary excretion of Phe, consistent with SLC6A19 inhibition and target engagement. In the SAD portion of the study, a single 960 mg dose resulted in an approximately 39-fold increase in urinary Phe excretion relative to baseline. In the MAD cohorts, administration of 240 mg twice daily for seven days resulted in an approximately 42-fold increase in urinary Phe excretion on Day 7. At lower dose levels, including 120 mg once daily, MZE782 produced an approximately 12-fold increase in urinary Phe excretion.

Prior to study initiation, we defined a 10-fold increase in urinary Phe excretion as a pharmacodynamic benchmark for meaningful SLC6A19 inhibition. This benchmark was exceeded across multiple well-tolerated dose levels in both single and multiple ascending dose cohorts. These findings support further evaluation of MZE782 as a potential substrate reduction therapy in patients with PKU.

Based on these results, we plan to initiate a Phase 2 proof-of-concept trial of MZE782 evaluating plasma Phe reduction in patients with PKU in mid-2026. Subchronic GLP toxicology studies (13-week) were performed in two species to support dose selection. Limited infiltration of inflammatory cells surrounding small and medium blood vessels, at doses well above the clinical dose range, were observed. However, these do not impact dose selection for Phase 2.

10

MZE782 – Chronic Kidney Disease (CKD)

Indication and Unmet Need

Our third program consists of MZE782 as an investigational therapy targeting SLC6A19 for the treatment of CKD. SLC6A19 encodes the protein BoAT1, a sodium-dependent neutral amino acid transporter expressed primarily in the proximal tubule of the kidney and on the brush border of the small intestine. In the kidney, SLC6A19 plays a role in minimizing the excretion of amino acids in urine by transporting these key nutrients from the urine back into the bloodstream. We identified SLC6A19 as a potential therapeutic target based on human genetic findings demonstrating that loss-of-function variants in SLC6A19 are associated with improved renal function and protection from CKD.

CKD affects approximately 37 million patients in the United States and an estimated 700 million patients worldwide. It is expected to become the fifth most prevalent chronic disease in the United States by 2040. CKD manifests through various stages, culminating in ESKD, which necessitates dialysis or kidney transplantation for survival. As of 2018, the five-year survival rate for patients in the United States who initiated dialysis was under 50%. As kidney function diminishes, patients may develop hypertension, anemia, muscle weakness, nerve damage, kidney failure, and cardiovascular disease. Depending on the stage of disease and the age of the patient, up to 50% of patients diagnosed with CKD may also experience heart failure. These complications contribute to premature mortality and increased healthcare utilization.

In addition to its impact on patients and their families, CKD places a substantial burden on the healthcare system. More than 550,000 patients in the United States require dialysis, and approximately 230,000 patients are living with a kidney transplant. Medicare spends more than 24% of its total annual expenditures, or approximately $130 billion, on patients with CKD.

Current treatments for CKD focus on slowing disease progression, but do not target underlying genetic drivers of disease. In addition to lifestyle modifications, the standard of care includes renin-angiotensin-aldosterone system inhibitors, or RAASi, sodium-glucose cotransporter-2 inhibitors, or SGLT2i, and glucagon-like peptide-1 receptor agonists, as well as medications to control blood pressure, blood glucose, anemia, bone and mineral disorders, and fluid overload. While these therapies have improved outcomes, response remains inadequate in a substantial subset of patients. Many patients continue to experience progressive loss of kidney function and remain at risk of ESKD.

Of the approximately 14 million patients in the United States with clinical symptoms requiring treatment, only approximately seven million are currently receiving therapy. Among treated patients, we estimate that up to five million may have an inadequate response to existing therapies. Approximately 25% of patients respond inadequately to SGLT2i therapies. In addition, SGLT2i treatment has been associated with increased risk of diabetic ketoacidosis and urinary tract infections, which may limit uptake or lead to discontinuation in certain patients.

Given the escalating prevalence of CKD, persistent gaps in treatment response, and the substantial clinical and economic burden of disease, there remains a critical need for innovative therapies capable of improving renal outcomes and addressing patients who are inadequately controlled on current standard of care. MZE782 is being developed to reduce proteinuria and slow progression to ESKD in patients inadequately controlled on standard of care. MZE782 may also have potential for use as an add-on therapy in combination with existing treatments. By targeting SLC6A19 through a mechanism distinct from currently available therapies, this approach is intended to address persistent gaps in chronic kidney disease treatment.

Mechanism of Action

Using our Compass platform, we identified SLC6A19 as a therapeutic target through genetic association analyses demonstrating a bidirectional allelic series that included variants associated with either improved or worsened renal function. SLC6A19 encodes the sodium-dependent neutral amino acid transporter BoAT1, which is expressed primarily in the proximal tubule of the kidney and on the brush border of the small intestine.

SLC6A19 emerged as a novel therapeutic target based on analyses of independent sets of human genetic data matched with longitudinal clinical data for kidney health. In the UK Biobank dataset, SLC6A19 variants plotted by allele frequency were statistically significantly associated (p < 5 × 10⁻8) with changes in kidney function as measured by serum creatinine. One loss-of-function missense variant, D173N, demonstrated the largest beneficial effect on kidney function as determined by serum creatinine and cystatin C and increased estimated glomerular filtration rate, consistent with improved kidney function. In contrast, genetic variants associated with higher SLC6A19 expression were associated with worsened biomarker profiles. These directionally opposite effects across multiple biomarkers support a model in which reduced SLC6A19 activity is protective in chronic kidney disease.

We used the Compass platform to identify an additional set of loss-of-function variants in SLC6A19, which increased our power to perform genetic association tests in cohorts of patients with CKD. In a combined analysis of patients with CKD in the UK Biobank and GCKD cohorts, carrying a single loss-of-function allele in SCL6A19 resulted in an almost 50% decrease risk of progression to the composite renal endpoint used in registrational CKD trials. This analysis demonstrated that loss of a single copy of SLC6A19 activity (representing a 50% reduction in activity) is associated with slower disease progression and increases our confidence that inhibition will be therapeutically relevant.

11

SLC6A19 functions in the proximal tubule to reabsorb neutral amino acids from the filtrate back into the bloodstream in a sodium-dependent manner. MZE782 is designed as a small molecule inhibitor intended to phenocopy the protective effects observed in individuals carrying reduced-function SLC6A19 variants.

Inhibition of SLC6A19 reduces reabsorption of neutral amino acids and modulates sodium handling within the proximal tubule. Similar to SGLT2i therapy, reduced proximal tubular sodium reabsorption may enhance tubulo-glomerular feedback and decrease intraglomerular pressure, a mechanism that has become foundational in current chronic kidney disease therapies. Because SLC6A19 operates through a distinct transporter pathway, this mechanism may be complementary to, and potentially independent of, SGLT2i therapy.

In addition to its potential renal hemodynamic effects, inhibition of SLC6A19 may alter the reabsorption of additional solutes and metabolites in the proximal tubule. By reducing reuptake of certain metabolites, SLC6A19 inhibition may decrease intracellular accumulation of potentially harmful compounds within kidney cells, thereby reducing cellular stress and injury. This proposed detoxification pathway represents a mechanism distinct from glucose transport inhibition.

Clinical development status

In September 2025, we reported results from our Phase 1 clinical trial of MZE782, as described above in MZE782 – Phenylketonuria (PKU) - Clinical development status.

As previously described, MZE782 produced dose-dependent increases in 24-hour urinary excretion of the neutral amino acids Phe and Gln, across both SAD and MAD cohorts, confirming target engagement and SLC6A19 inhibition. In addition, we conducted exploratory analyses of renal function parameters, including estimated eGFR. With established reno-protective therapies, including RAASi and SGLT2i therapies and mineralocorticoid antagonists, treatment is typically associated with a small, initial decline in eGFR. This acute change is generally understood to reflect a transient renal hemodynamic effect consistent with reduced intraglomerular pressure. Over time, this initial change has been associated with a slower rate of eGFR decline compared to placebo across multiple therapeutic classes and patient populations. In the Phase 1 study, MZE782 demonstrated a dose-dependent acute change in eGFR consistent with modulation of proximal tubular sodium handling and tubulo-glomerular feedback. Exploratory analyses of eGFR showed a sustained decrease in eGFR over the treatment period that reversed upon discontinuation of MZE782, further supporting an MZE782-related acute effect. These renal function analyses were exploratory in nature, and the study was not designed to evaluate long-term effects on kidney function. Further evaluation of these findings is planned in future clinical studies in patients with CKD.

We plan to initiate a Phase 2 proof-of-concept trial of MZE782 in CKD in the second half of 2026

Additional kidney and metabolic research programs

In addition to our clinical programs, we are exploring additional targets using our Compass approach.

Our partnered programs

Using our Compass platform, we have validated targets and new therapeutic approaches targeting diseases outside of our core focus areas, including neurology, ophthalmology and rare diseases. We have entered into partnership arrangements with third parties with respect to several of these targets. These programs are not only sources of revenue, but also demonstrate the power of our Compass platform.

Rare Disease: GYS1 (MZE001) for Pompe disease

MZE001 was our first clinical program and is an investigational oral small molecule inhibitor of muscle-specific glycogen synthase (glycogen synthase 1, or GYS1), designed to reduce glycogen accumulation in muscle tissue as a potential substrate reduction therapy for Pompe disease.

Pompe disease is a rare, inherited lysosomal storage disorder caused by mutations in the gene encoding acid alpha-glucosidase, resulting in accumulation of glycogen in skeletal, respiratory and cardiac muscle and leading to progressive muscle weakness and respiratory compromise. Approximately 50,000 patients are estimated to be living with Pompe disease worldwide.

In December 2022, we completed a randomized, double-blind, placebo-controlled single and multiple ascending dose Phase 1 clinical trial of MZE001 in 129 healthy volunteers. The study evaluated safety, tolerability and pharmacokinetics, with exploratory assessments of biomarkers of glycogen metabolism. MZE001 was well tolerated at all dose levels tested, with no serious adverse events reported. Exploratory analyses demonstrated inhibition of muscle glycogen synthesis and reduction of total muscle glycogen compared to placebo.

12

In March 2024, we exclusively licensed MZE001 to Shionogi. Under the terms of the agreement, Shionogi received an exclusive, worldwide, sublicensable license to research, develop, manufacture and commercialize MZE001 and related compounds. We received an upfront payment of $150 million and are eligible to receive additional development, regulatory and commercial milestone payments, as well as tiered royalties on future net sales.

Neurology: ATXN2 and UNC13A

ATXN2.

In preclinical studies, we identified ATXN2 as a genetic modifier of amyotrophic lateral sclerosis. Inhibition of ATXN2 was shown in model systems to limit toxicity associated with TDP-43, a protein found to be pathologically aggregated in the majority of amyotrophic lateral sclerosis patients. Using our functional genomics and human genetics capabilities, we developed a microRNA gene therapy designed to reduce ATXN2 expression.

In May 2024, we exclusively licensed our ATXN2 program to Neurocrine Biosciences, Inc. As consideration for such license, we received upfront payment, and we will be eligible to receive milestone payments upon the completion of certain regulatory, development and commercial achievements, as well as royalties based upon future annual net sales.

UNC13A.

Genome-wide association studies have identified variants in the UNC13A gene as risk factors for amyotrophic lateral sclerosis and frontotemporal dementia. We and our collaborators identified a link between UNC13A genetic variation and TDP-43–associated pathology. These findings were published in Nature and were further supported by in vitro studies demonstrating that loss of nuclear TDP-43 leads to cryptic exon formation in UNC13A and reduced UNC13A protein levels.

In April 2024, we exclusively licensed the UNC13A program to Trace Neuroscience, Inc. In connection with the license, we received an upfront payment and are eligible to receive development, regulatory and commercial milestone payments, as well as royalties on future net sales.

Ophthalmology: ANGPTL7 for glaucoma

Through application of our Compass platform, we identified ANGPTL7 as a genetically validated target associated with intraocular pressure and glaucoma risk. Human genetic analyses identified rare protein-altering variants in ANGPTL7 that were associated with lower intraocular pressure and reduced risk of glaucoma.

In November 2020, together with Alloy Therapeutics, Inc., or Alloy, we formed Broadwing, a spin-out company to develop antibody therapies targeting ANGPTL7 and an additional genetically validated ophthalmic target. We contributed cash and in-kind services in exchange for an initial 50% equity interest, and Alloy contributed cash and antibody discovery services for the remaining 50% equity interest.

As of December 31, 2025, we owned approximately 48% of the outstanding equity of Broadwing. We expect our ownership percentage to be diluted upon conversion of outstanding convertible notes issued by Broadwing.

Competition

The pharmaceutical and biotechnology industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on intellectual property. While we believe that our Compass platform and our knowledge, experience and scientific resources provide us with competitive advantages, we face potential competition from major pharmaceutical and biotechnology companies, academic institutions, government agencies and private and public research institutions, among others.

Any therapeutic candidates that we or our partners successfully develop and commercialize may compete with existing therapies and new therapies that may become available in the future that are approved to treat the same indications for which we or our partners may obtain approval for our or their therapeutic candidates. It is also possible that we or our partners may face competition from other pharmaceutical approaches as well as other types of therapies. The key competitive factors affecting the success of all our programs, if approved, include, but are not limited to be their efficacy, safety, convenience, adoption by prescribers, price, level of generic competition, and availability of reimbursement.

We may face competition from companies developing therapies for CKD and related nephropathies, including but not limited to:

•
Established therapies: including RAAS inhibitors, SGLT2 inhibitors and GLP-1 receptor agonists.

13

•
Novel mechanisms: various companies developing therapies targeting different pathways implicated in CKD progression.

While there are currently no approved therapies for AMKD, we are aware of companies advancing therapeutic candidates in clinical trials that target APOL1.

Our second most advanced program, MZE782, is a small molecule targeting SLC6A19, a novel target in CKD and PKU. While there are no currently approved therapies directly modulating SLC6A19, we may face competition from other companies pursuing programs targeting SLC6A19 or alternative approaches for renal indications.

Many of our current or potential competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Mergers and acquisitions in the biopharmaceutical industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through partnership arrangements with large and established companies.

Further, precision medicine is a rapidly developing field, with increasing usage within the pharmaceutical and biotechnology industry of machine learning and artificial intelligence, or AI, technologies to analyze genetic data. While we believe our Compass platform has advantages over potential competitors based on our experience in variant functionalization, our access to genetic databases, and the length of time that we have been engaged in developing precision medicine, other companies may have greater resources or the ability to acquire more advanced technology to identify targets and may acquire access to the same genetic data that we utilize. We may not be able to keep up with the pace of innovation that is occurring in our field, and we may face increasing competition in developing precision medicines.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain United States Food and Drug Administration, or FDA, or other applicable regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

Intellectual property

Intellectual property is of vital importance in our field and in biotechnology generally. We seek to protect and enhance proprietary technologies, inventions, and improvements that are commercially important to the development of our business by seeking, maintaining, and defending intellectual property rights, including patent rights. We may also seek to rely on regulatory protection afforded through inclusion in expedited development and review, data exclusivity, market exclusivity and/or patent term extensions where available.

Our commercial success will depend in part on obtaining and maintaining patent protection of our current and future therapeutic candidates and the methods used to develop and manufacture them, as well as successfully defending our patents against third-party challenges, and operating without infringing on, misappropriating or otherwise violating the intellectual property and proprietary rights of others. The development of our therapeutic candidates is at a relatively early stage and as a consequence, our patent portfolio is also at an early stage. We cannot be sure that patents will be granted based on our currently pending patent applications or patent applications we may file in the future. Nor can we be sure that any of our granted patents or patents that may be granted to us in the future will be commercially useful in protecting our therapeutic candidates, technologies and processes. In addition, any patents that we may hold, whether owned or licensed, may be challenged, circumvented or invalidated by third parties.

The term of individual patents depends upon the law in the countries in which they are obtained. In most countries, including the United States, the term of a patent is 20 years from the earliest date of filing a non-provisional patent application, unless otherwise extended or adjusted. U.S. non-provisional applications and/or Patent Cooperation Treaty, or PCT, applications may be filed that claim priority to an earlier-filed patent application, provided that the earlier-filed patent application was filed within 12 months of the U.S. non-provisional or PCT filing date. The PCT system allows for the designation of PCT member states in which national or regional patent applications may later be pursued. A PCT application cannot mature into a patent until, among other things, one or more national or regional stage patent applications are filed within the applicable time limit, which is generally 30 or 31 months from the PCT application’s earliest priority date, depending on the jurisdiction.

14

The ability to obtain patent protection and the degree of such protection depends on several factors, including whether an invention is directed to patentable subject matter, the novelty and non-obviousness of the claimed invention, and the ability to satisfy the requirements of applicable patent laws, such as enablement and written description, in addition to other administrative requirements for obtaining a patent. In addition, the claim scope in a patent application may be significantly narrowed before a patent is issued, and the scope of issued claims can be reinterpreted or further altered even after patent issuance. Consequently, we may not obtain or maintain adequate patent protection for any of our proprietary technologies or current or future therapeutic candidates.

In addition to patent protection, we also rely on trade secrets, know-how, other proprietary information and continuing technological innovation to develop and maintain our competitive position. We seek to protect and maintain the confidentiality of trade secrets and other proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. For example, we seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. However, such security measures may be breached and we may not have adequate remedies for such breaches. We also seek to protect our proprietary information and trade secrets by entering into confidentiality and invention assignment agreements with our employees, consultants and other parties who have access to such information. These agreements generally provide that all confidential information concerning our business or financial affairs developed or made known to the individual during the course of the individual’s relationship with us is to be kept confidential and not disclosed to third parties except in specific circumstances. Our agreements with employees also generally provide that all inventions conceived by the employee in the course of employment with us or from the employee’s use of our confidential information are our exclusive property. However, we cannot guarantee that we have entered into such agreements with each party that has or may have had access to our trade secrets or other proprietary information or has been involved in the development of intellectual property. Additionally, these agreements can be breached and we may not have adequate remedies for any such breach. Moreover, our trade secrets may otherwise become known or be independently discovered by competitors, and to the extent that our employees, consultants, contractors or partners use intellectual property or proprietary information owned by others in their work for us, disputes may arise as to our intellectual property rights. For all of these reasons, we may not be able to adequately protect proprietary information, trade secrets, know-how and inventions important to the development of our business.

The intellectual property positions of biotechnology companies like ours are generally uncertain and involve complex legal, scientific and factual questions. Our commercial success will also depend in part on avoiding infringing upon, misappropriating or otherwise violating the intellectual property and proprietary rights of third parties. Third-party patents could require us to alter our development or commercial strategies, or our products or processes, obtain licenses or cease certain activities. Our breach of any license agreements or our failure to obtain a license to proprietary rights required to develop or commercialize our future products may have a material adverse impact on us. For more information regarding the risks related to intellectual property, see “Risk Factors—Risks related to intellectual property.”

Our policy is to seek patent protection for the technologies, inventions and improvements that we develop and that we consider important to the advancement of our business.

For our small molecule APOL1 program, as of March 15, 2026, we own patent families that cover composition of matter of our APOL1 compounds, including MZE829, methods of use, and processes. These patent families include two issued U.S. patents, three pending U.S. provisional patent applications, three pending PCT patent applications, eight pending U.S. non-provisional patent applications, and over forty-five pending foreign patent applications in various jurisdictions including but not limited to Australia, Brazil, Canada, China, the European Patent Office, Hong Kong, Israel, India, Japan, Republic of Korea, Mexico, Saudi Arabia, Singapore, and Taiwan. Any currently issued patents or patents that may issue in the future from these applications in our APOL1 program are projected to expire between 2042 and 2046 unless extended or otherwise adjusted.

For our small molecule SLC6A19 program, as of March 15, 2026, we own patent families that cover composition of matter of our SLC6A19 compounds, including MZE782, methods of use, and processes. These patent families include four pending U.S. provisional patent applications, six pending PCT patent applications, four pending U.S non-provisional patent applications, and over thirty-five pending foreign patent applications in various jurisdictions including but not limited to Australia, Brazil, Canada, China, the European Patent Office, Israel, India, Japan, Republic of Korea, Mexico, Saudi Arabia, Singapore, and Taiwan. Any currently issued patents or patents that may issue in the future from these applications in our SLC6A19 program are projected to expire between 2043 and 2047 unless extended or otherwise adjusted.

We have entered into three agreements to exclusively license or assign our patent portfolios associated with programs that are outside our areas of core focus. Pursuant to these agreements, we no longer have control of the prosecution of the issued patents and pending patent applications in each of these portfolios. We cannot guarantee that our licensees will successfully develop, obtain marketing authorization for, or commercialize products that would result in our receiving royalties pursuant to such license agreements.

15

We have exclusively licensed our GYS1 patent portfolio, which includes an issued U.S. patent covering MZE001, to Shionogi. At the time we entered into the License Agreement, our GYS1 patent portfolio included a pending U.S. non-provisional patent application, three pending PCT applications, and over twenty-five pending foreign patent applications in various jurisdictions including but not limited to Australia, Brazil, Canada, China, the European Patent Office, Hong Kong, Israel, India, Japan, Republic of Korea, Mexico, Russia, Saudi Arabia, Singapore, and Taiwan. The patent portfolio we licensed to Shionogi is directed to compositions of matter, uses and processes, and any currently issued patents or patents that may issue in the future in this portfolio are projected to expire between 2042 and 2043 unless extended or otherwise adjusted. Shionogi controls the prosecution of this patent portfolio.

We have exclusively licensed our patent portfolio relating to our program for ATXN2 gene therapy to another biotechnology company who controls the prosecution of this portfolio. At the time we entered into this agreement, no patents had been issued. Our ATXN2 gene therapy patent portfolio included two pending non-provisional patent applications and over fifteen pending foreign patent applications in various jurisdictions. The ATXN2 gene therapy patent portfolio is directed to compositions of matter and uses, and any patents that may issue in the future in this portfolio are projected to expire between 2041 and 2042 unless extended or otherwise adjusted.

In addition to our owned and out-licensed patent portfolios described above, we assigned our UNC13A ASO patent portfolio in April 2024 to another biotechnology company.

Manufacturing

We do not have any clinical manufacturing facilities. We currently rely, and expect to continue to rely, on third party contract manufacturing organizations, or CMOs, including foreign CMOs, for clinical manufacturing of MZE829, MZE782 and our future therapeutic candidates, as well as for commercial manufacturing if our therapeutic candidates receive marketing approval.

We use multiple CMOs, including foreign CMOs, to manufacture our clinical-stage therapeutic candidates to conduct our clinical trials. As part of our strategy, we seek to develop or advance therapeutic candidates that can be produced cost-effectively at contract manufacturing facilities without the need for unusual manufacturing equipment. All of our current therapeutic candidates are small molecule drug products that we believe will require between 12 and 14 months to manufacture from initiation of drug substance manufacturing to completion of drug product, assuming we are able to obtain manufacturing slots with the appropriate CMOs.

We expect to enter into commercial supply agreements with commercial manufacturers prior to any potential approval of any of our therapeutic candidates. We believe our current CMOs are able to adequately support manufacturing for our current and planned clinical trials and additional CMOs may be onboarded at later stages of clinical development and commercialization.

To the extent any of our therapeutic candidates require companion diagnostics, which are assays or tests to identify an appropriate patient population, we generally rely, and expect to continue to rely, on third parties to manufacture such assays or tests.

Governmental regulation and product approval

Government authorities in the United States, at the federal, state and local level, and in other countries and jurisdictions, extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of pharmaceutical products. The processes for obtaining regulatory approvals in the United States and in foreign countries and jurisdictions, along with subsequent compliance with applicable statutes and regulations and other regulatory authorities, require the expenditure of substantial time and financial resources.

FDA approval process

In the United States, pharmaceutical products are subject to extensive regulation by the FDA. The Federal Food, Drug, and Cosmetic Act, or FDCA, and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling, and import and export of pharmaceutical products. Pharmaceutical products—such as small molecule drugs and biological products, or biologics—used for the prevention, treatment, or cure of a disease or condition of a human being are subject to regulation under the FDCA. Failure to comply with applicable United States requirements may subject a company to a variety of administrative or judicial sanctions, such as clinical hold, FDA refusal to approve pending new drug applications, or NDAs, warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, and criminal prosecution.

16

Pharmaceutical product development for a new product or certain changes to an approved product in the United States typically involves preclinical laboratory and animal tests, the submission to the FDA of an Investigational New Drug Application, or IND, which must become effective before clinical testing may commence, and adequate and well-controlled clinical trials to establish the safety and effectiveness of the drug for each indication for which FDA approval is sought. Satisfaction of FDA pre-market approval requirements typically takes many years and the actual time required may vary substantially based upon the type, complexity, and novelty of the product or disease.

Preclinical tests include laboratory evaluation of product chemistry, formulation, and toxicity, as well as animal trials to assess the characteristics and potential safety and efficacy of the product. The conduct of the preclinical tests must comply with federal regulations and requirements, including Good Laboratory Practices.

The results of preclinical testing are submitted to the FDA as part of an IND along with other information, including information about product chemistry, manufacturing and controls, and a proposed clinical trial protocol. Long-term nonclinical tests, such as tests of reproductive toxicity and carcinogenicity in animals, may continue after the IND is submitted. A 30-day waiting period after the submission of each IND is required prior to the commencement of clinical testing in humans. If the FDA has neither commented on nor questioned the IND within this 30-day period, the clinical trial proposed in the IND may begin. Clinical trials involve the administration of the investigational drug to healthy volunteers or patients under the supervision of a qualified investigator. Clinical trials must be conducted: (i) in compliance with federal regulations; (ii) in compliance with GCP, an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators, and monitors; as well as (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. Each protocol involving testing on U.S. patients and subsequent protocol amendments must be submitted to the FDA as part of the IND.

The FDA may order the temporary or permanent discontinuation of a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial either is not being conducted in accordance with FDA regulations or presents an unacceptable risk to the clinical trial patients. Imposition of a clinical hold may be full or partial. The study protocol and informed consent information for patients in clinical trials must also be submitted to an Institutional Review Board, or IRB, for approval. The IRB will also monitor the clinical trial until completed. The IRB may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements, or may impose other conditions. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether a trial may move forward at designated checkpoints based on access to certain data from the trial.

Clinical trials to support NDAs for marketing approval are typically conducted in three sequential phases, but the phases may overlap. In Phase 1, the initial introduction of the drug into healthy human subjects or patients, the product is tested to assess safety, dosage tolerance, metabolism, PK, pharmacological actions, side effects associated with drug exposure, and to obtain early evidence of a treatment effect if possible. Phase 2 usually involves trials in a limited patient population to determine the effectiveness of the drug for a particular indication, determine optimal dose and regimen, and to identify common adverse effects and safety risks. If a compound demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain additional information about clinical effects and confirm efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the product. In many cases, particularly for prevalent diseases, the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the safety and efficacy of the drug. In many other conditions, particularly for rare diseases, a single Phase 3 trial may also be sufficient in conjunction with confirmatory evidence. A single adequate and well-controlled trial may also be sufficient, though it is less common, when the trial is a large, multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically. Approval on the basis of a single trial may be subject to a requirement for additional post-approval studies.

In addition, the manufacturer of an investigational drug in a Phase 2 or Phase 3 clinical trial for a serious or life-threatening disease is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for expanded access to such investigational drug.

17

After completion of the required clinical testing, an NDA is prepared and submitted to the FDA. FDA approval of the NDA is required before marketing and distribution of the product may begin in the United States. The NDA must include the results of all preclinical, clinical, and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture, and controls. The cost of preparing and submitting an NDA is substantial. The submission of most NDAs is additionally subject to a substantial application user fee. Under an approved NDA, the applicant is also subject to an annual program fee. These fees typically increase annually. The FDA has 60 days from its receipt of an NDA to determine whether the application will be filed based on the FDA’s determination that it is adequately organized and sufficiently complete to permit substantive review. Once the submission is filed, the FDA begins an in-depth review. The FDA has agreed to certain performance goals to complete the review of NDAs. Most applications are classified as Standard Review products that are reviewed within ten months of the date the FDA files the NDA; applications classified as Priority Review are reviewed within six months of the date the FDA files the NDA. An NDA can be classified for Priority Review when the FDA determines the drug has the potential to treat a serious or life-threatening condition and, if approved, would be a significant improvement in safety or effectiveness compared to available therapies. The review process for both standard and priority reviews may be extended by the FDA for three months to consider information the FDA considers to be a major amendment to the NDA.

The FDA may also refer applications for novel drugs, as well as drug products that present difficult questions of safety or efficacy, to be reviewed by an advisory committee—typically a panel that includes clinicians, statisticians and other experts—for review, evaluation, and a recommendation as to whether the NDA should be approved. The FDA is not bound by the recommendation of an advisory committee, but generally follows such recommendations. Before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will inspect the facility or the facilities at which the drug product is manufactured. The FDA will not approve the product unless compliance with current good manufacturing practices, or cGMPs, is satisfactory and the NDA contains data that provide substantial evidence that the drug is safe and effective in the claimed indication.

After the FDA evaluates the NDA and completes any clinical and manufacturing site inspections, it issues either an approval letter or a complete response letter. A complete response letter generally outlines the deficiencies in the NDA submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application for approval. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included. An approval letter authorizes commercial marketing and distribution of the drug with specific prescribing information for specific indications. As a condition of NDA approval, the FDA may require a Risk Evaluation and Mitigation Strategy, or REMS, to help ensure that the benefits of the drug outweigh the potential risks to patients. A REMS can include medication guides, communication plans for healthcare professionals, and elements to assure a product’s safe use, or ETASU. An ETASU can include, but is not limited to, special training or certification for prescribing or dispensing the product, dispensing the product only under certain circumstances, special monitoring, and the use of patient-specific registries. The requirement for a REMS can materially affect the potential market and profitability of the product. Moreover, the FDA may require substantial post-approval testing and surveillance to monitor the product’s safety or efficacy.

Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing. Changes to some of the conditions established in an approved NDA, including changes in indications, product labeling, manufacturing processes or facilities, require submission and FDA approval of a new NDA, or supplement to an approved NDA, before the change can be implemented. An NDA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDA supplements as it does in reviewing original NDAs.

Fast track designation and priority review

FDA is required to facilitate the development, and expedite the review, of drugs that are intended for the treatment of a serious or life-threatening disease or condition for which there is no effective treatment and which demonstrate the potential to address unmet medical needs for the condition. Fast track designation may be granted for products that are intended to treat a serious or life-threatening disease or condition for which there is no effective treatment and preclinical or clinical data demonstrate the potential to address unmet medical needs for the condition. Fast track designation applies to both the product and the specific indication for which it is being studied. Any product submitted to FDA for marketing, including under a fast track program, may be eligible for other types of FDA programs intended to expedite development and review, such as priority review.

Priority review may be granted for products that are intended to treat a serious or life-threatening condition and, if approved, would provide a significant improvement in safety and effectiveness compared to available therapies. FDA will attempt to direct additional resources to the evaluation of an application designated for priority review in an effort to facilitate the review.

18

Accelerated approval

Accelerated approval may be granted for a product that is intended to treat a serious or life-threatening condition and that generally provides a meaningful therapeutic advantage to patients over existing treatments. A product eligible for accelerated approval may be approved on the basis of either a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. In clinical trials, a surrogate endpoint is a measurement of laboratory or clinical signs of a disease or condition that substitutes for a direct measurement of how a patient feels, functions, or survives. The accelerated approval pathway is most often used in settings in which the course of a disease is long and an extended period of time is required to measure the intended clinical benefit of a product, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly. Thus, accelerated approval has been used extensively in the development and approval of products for treatment of a variety of cancers in which the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large studies to demonstrate a clinical or survival benefit. The accelerated approval pathway is contingent on a sponsor’s agreement to conduct additional post-approval confirmatory studies to verify and describe the product’s clinical benefit. The FDA must specify conditions for the post-approval study which may include details regarding enrollment targets, the study protocol and study milestones. These confirmatory trials must be completed with due diligence and the FDA may require that the trial be designed, initiated, and/or fully enrolled prior to submission of the application or approval. Sponsors are also required to submit regular reports regarding the progress of conducting these post-approval studies. Failure to conduct required post-approval studies in accordance with FDA’s conditions and with due diligence, or submit the progress reports as well as failure to confirm a clinical benefit during post-marketing studies, would allow the FDA to undertake enforcement action or withdraw the product from the market on an expedited basis. All promotional materials for product candidates approved under accelerated approval regulations are subject to prior review by the FDA.

Disclosure of clinical trial information

Sponsors of clinical trials of FDA-regulated products, including drugs, are required to register and disclose certain clinical trial information on the website www.clinicaltrials.gov. Information related to the product, patient population, phase of investigation, trial sites and investigators, and other aspects of a clinical trial are then made public as part of the registration. Sponsors are also obligated to disclose the results of their clinical trials after completion. Disclosure of the results of clinical trials can be delayed in certain circumstances for up to two years after the date of completion of the trial. Competitors may use this publicly available information to gain knowledge regarding the progress of clinical development programs as well as clinical trial design.

Pediatric information

Under the Pediatric Research Equity Act, or PREA, NDAs or supplements to NDAs must contain data to assess the safety and effectiveness of the drug for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the drug is safe and effective. The FDA may grant full or partial waivers, or deferrals, for submission of data. Unless otherwise required by regulation, PREA does not apply to any drug with orphan product designation except a product with a new active ingredient that is a molecularly targeted cancer product intended for the treatment of an adult cancer and directed at a molecular target determined by FDA to be substantially relevant to the growth or progression of a pediatric cancer that is subject to an NDA submitted on or after August 18, 2020.

The Best Pharmaceuticals for Children Act, or BPCA, provides a six-month extension of any exclusivity-patent or non-patent-for a drug if certain conditions are met. Conditions for exclusivity include the FDA’s determination that information relating to the use of a new drug in the pediatric population may produce health benefits in that population, FDA making a written request for pediatric studies, and the applicant agreeing to perform, and reporting on, the requested studies within the statutory timeframe. Applications under the BPCA are treated as priority applications, with all of the benefits that designation confers.

Post-approval requirements

Once an NDA is approved, a product will be subject to certain post-approval requirements. For instance, the FDA closely regulates the post-approval marketing and promotion of drugs, including standards and regulations for direct-to-consumer advertising, off-label promotion, industry-sponsored scientific and educational activities and promotional activities involving the Internet. Drugs may be marketed only for the approved indications and in accordance with the provisions of the approved labeling.

Adverse event reporting and submission of periodic safety summary reports are required following FDA approval of an NDA. The FDA also may require post-marketing testing, known as Phase 4 testing, REMS, and surveillance to monitor the effects of an approved product, or the FDA may place conditions on an approval that could restrict the distribution or use of the product. In addition, quality control, drug manufacture, packaging, and labeling procedures must continue to conform to cGMPs after approval.

19

Drugs manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies. Registration with the FDA subjects entities to periodic unannounced inspections by the FDA, during which the agency inspects a drug’s manufacturing facilities to assess compliance with cGMPs. Accordingly, manufacturers must continue to expend time, money, and effort in the areas of production and quality-control to maintain compliance with cGMPs. Regulatory authorities may withdraw product approvals or request product recalls if a company fails to comply with required regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized problems are subsequently discovered.

The Hatch-Waxman amendments

Orange book listing

Under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch Waxman Amendments, NDA applicants are required to identify to FDA each patent whose claims cover the applicant’s drug or approved method of using the drug. Upon approval of a drug, the applicant must update its listing of patents to the FDA in timely fashion and each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book.

Drugs listed in the Orange Book can, in turn, be cited by potential generic competitors in support of approval of an abbreviated NDA, or ANDA. An ANDA provides for marketing of a drug product that has the same active ingredient(s), strength, route of administration, and dosage form as the listed drug and has been shown through bioequivalence testing to be therapeutically equivalent to the listed drug. An approved ANDA product is considered to be therapeutically equivalent to the listed drug. Other than the requirement for bioequivalence testing, ANDA applicants are not required to conduct, or submit results of, preclinical or clinical tests to prove the safety or effectiveness of their drug product. Drugs approved under the ANDA pathway are commonly referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions written for the original listed drug pursuant to each state’s laws on drug substitution.

The ANDA applicant is required to certify to the FDA concerning any patents identified for the reference listed drug in the Orange Book. Specifically, the applicant must certify to each patent in one of the following ways: (i) the required patent information has not been filed; (ii) the listed patent has expired; (iii) the listed patent has not expired but will expire on a particular date and approval is sought after patent expiration; or (iv) the listed patent is invalid, unenforceable or will not be infringed by the new product. A certification that the new product will not infringe the already approved product’s listed patents, or that such patents are invalid or unenforceable, is called a Paragraph IV certification. For patents listed that claim an approved method of use, under certain circumstances the ANDA applicant may also elect to submit a statement certifying that its proposed ANDA label does not contain (or carves out) any language regarding the patented method-of-use rather than certify to a listed method-of-use patent, which is called a Section VIII statement. If the applicant does not challenge the listed patents through a Paragraph IV certification, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired. If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA-holder and patentee(s) once the ANDA has been accepted for filing by the FDA (referred to as the “notice letter”). The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice letter. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months from the date the notice letter is received, expiration of the patent, the date of a settlement order or consent decree signed and entered by the court stating that the patent that is the subject of the certification is invalid or not infringed, or a decision in the patent case that is favorable to the ANDA applicant.

The ANDA application also will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired. In some instances, an ANDA applicant may receive approval prior to expiration of certain non-patent exclusivity if the applicant seeks, and FDA permits, the omission of such exclusivity-protected information from the ANDA prescribing information.

Exclusivity

Upon NDA approval of a new chemical entity, or NCE, which is a drug that contains no active moiety that has been approved by FDA in any other NDA, that drug receives five years of marketing exclusivity during which FDA cannot receive any ANDA seeking approval of a generic version of that drug unless the application contains a Paragraph IV certification, in which case the application may be submitted one year prior to expiration of the NCE exclusivity. If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no ANDA for a generic version of the drug may be filed before the expiration of the exclusivity period.

20

Certain changes to an approved drug, such as the approval of a new indication, the approval of a new strength, and the approval of a new condition of use, are associated with a three-year period of exclusivity from the date of approval during which FDA cannot approve an ANDA for a generic drug that includes the change. In some instances, an ANDA applicant may receive approval prior to expiration of the three-year exclusivity if the applicant seeks, and FDA permits, the omission of such exclusivity-protected information from the ANDA package insert.

Patent term extension

The Hatch Waxman Amendments permit a patent term extension as compensation for patent term lost during the FDA regulatory review process. Patent term extension, however, cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date. After NDA approval, owners of relevant drug patents may apply for the extension. The allowable patent term extension depends on a number of factors and is on a case by case basis, generally calculated as half of the drug’s testing phase (the time between IND application and NDA submission) and all of the review phase (the time between NDA submission and approval) that occurs after patent issuance up to a maximum of five years and subject to the 14 year cap. The time can be reduced for any time FDA determines that the applicant did not pursue approval with due diligence.

The United States Patent and Trademark Office, or USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. However, the USPTO may not grant an extension because of, for example, an applicant failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be less than requested.

The total patent term after the extension may not extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be enforced during the extension period. The application for the extension must be submitted prior to the expiration of the patent, and for patents that might expire during the application phase, the patent owner may request an interim patent extension. An interim patent extension increases the patent term by up to one year and may be renewed up to four times. For each interim patent extension granted, the post-approval patent extension is reduced by one year. The director of the USPTO must determine that approval of the drug covered by the patent for which a patent extension is being sought is likely. Interim patent extensions are not available for a drug for which an NDA has not been submitted.

FDA approval and regulation of companion diagnostics

If safe and effective use of a therapeutic product depends on an in vitro diagnostic, then the FDA generally will require approval or clearance of that diagnostic, known as a companion diagnostic, before or at the same time that the FDA approves the product. In August 2014, the FDA issued final guidance clarifying the requirements that will apply to approval of therapeutic products and in vitro companion diagnostics. According to the guidance, if FDA determines that a companion diagnostic device is essential to the safe and effective use of a new therapeutic product or indication, FDA generally will not approve the therapeutic product or new therapeutic product indication if the companion diagnostic device is not approved or cleared for that indication.

Approval or clearance of the companion diagnostic device will ensure that the device has been adequately evaluated and has adequate performance characteristics in the intended population. The review of in vitro companion diagnostics in conjunction with the review of a therapeutic product will, therefore, likely involve coordination of review by CDER and the FDA’s Office of In Vitro Diagnostics and Radiological Health.

Under the FDCA, in vitro diagnostics, including companion diagnostics, are regulated as medical devices. In the United States, the FDCA and its implementing regulations, and other federal and state statutes and regulations govern, among other things, medical device design and development, preclinical and clinical testing, premarket clearance or approval, registration and listing, manufacturing, labeling, storage, advertising and promotion, sales and distribution, export and import, and post-market surveillance. Unless an exemption applies, diagnostic tests require marketing clearance or approval from the FDA prior to commercial distribution. The two primary types of FDA marketing authorization applicable to a medical device are premarket notification, also called 510(k) clearance, and premarket approval, or PMA. The vast majority of companion diagnostics require PMA approval.

The PMA process, including the gathering of clinical and preclinical data and the submission to and review by the FDA, can take several years or longer. It involves a rigorous premarket review during which the applicant must prepare and provide the FDA with reasonable assurance of the device’s safety and effectiveness and information about the device and its components regarding, among other things, device design, manufacturing and labeling. PMA applications are subject to an application fee. In addition, PMAs for certain devices must generally include the results from extensive preclinical and adequate and well-controlled clinical trials to establish the safety and effectiveness of the device for each indication for which FDA approval is sought. In particular, for a

21

diagnostic, a PMA application typically requires data regarding analytical and clinical validation studies. As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality System Regulation, or QSR, which imposes elaborate testing, control, documentation and other quality assurance requirements.

PMA approval is not guaranteed, and the FDA may ultimately issue a not approvable letter to a PMA submission based on deficiencies in the application and require additional clinical trial or other data that may be expensive and time-consuming to generate and that can substantially delay approval. If the FDA’s evaluation of the PMA application is favorable, the FDA typically issues an approvable letter requiring the applicant’s agreement to specific conditions, such as changes in labeling, or specific additional information, such as submission of final labeling, in order to secure final approval of the PMA. If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not approvable letter. A not approvable letter will outline the deficiencies in the application and, where practical, will identify what is necessary to make the PMA approvable. The FDA may also determine that additional clinical trials are necessary, in which case the PMA approval may be delayed for several months or years while the trials are conducted and then the data submitted in an amendment to the PMA. If the FDA concludes that the applicable criteria have been met, the FDA will issue a PMA for the approved indications, which can be more limited than those originally sought by the applicant. The PMA can include post-approval conditions that the FDA believes necessary to ensure the safety and effectiveness of the device, including, among other things, restrictions on labeling, promotion, sale and distribution. Once granted, PMA approval may be withdrawn by the FDA if compliance with post approval requirements, conditions of approval or other regulatory standards are not maintained, or problems are identified following initial marketing.

After a device is placed on the market, it remains subject to significant regulatory requirements. Medical devices may be marketed only for the uses and indications for which they are cleared or approved. Device manufacturers must also register their establishments and list their devices with the FDA. A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QSR, which cover the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices. Domestic and foreign facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA.

Other U.S. healthcare laws and compliance requirements

In the United States, pharmaceutical and biotechnology company activities are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare & Medicaid Services, or CMS, other divisions of the U.S. Department of Health and Human Services, or HHS, (e.g., the Office of Inspector General and the Office for Civil Rights), the U.S. Department of Justice, or DOJ, and individual U.S. Attorney offices within the DOJ, and state and local governments. For example, sales, marketing and scientific/educational grant programs, may have to comply with the anti-fraud and abuse provisions of the Social Security Act, the federal false claims laws, the privacy and security provisions of the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, and similar state laws, each as amended, as applicable.

The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering, recommending or arranging for the purchase, lease or order of any item or service reimbursable under Medicare, Medicaid or other federal healthcare programs. The term remuneration has been interpreted broadly to include anything of value. The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, and/or formulary managers on the other. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution. The exceptions and safe harbors are drawn narrowly and practices that involve remuneration that may be alleged to be intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor. Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. Practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor. In addition, the statutory exceptions and regulatory safe harbors are subject to change.

Additionally, the intent standard under the Anti-Kickback Statute was amended by the ACA, to a stricter standard such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. In addition, the ACA codified case law that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act (discussed below).

The civil monetary penalties statute imposes penalties against any person or entity who, among other things, is determined to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.

22

Federal false claims laws, including the federal civil False Claims Act, prohibit, among other things, any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to, or approval by, the federal government or knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government. As a result of a modification made by the Fraud Enforcement and Recovery Act of 2009, a claim includes “any request or demand” for money or property presented to the U.S. government. In addition, manufacturers can be held liable under the civil False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. Pharmaceutical and other healthcare companies have been prosecuted under these laws for, among other things, allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. Other companies have been prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus generally non-reimbursable, uses and purportedly concealing price concessions in the pricing information submitted to the government for government price reporting purposes.

HIPAA created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services. Similar to the Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

Also, many states have similar fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

Data privacy and security regulations by both the federal government and the states in which business is conducted may also be applicable. HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, imposes among other things, certain requirements relating to the privacy, security, transmission and breach of individually identifiable health information. HIPAA requires covered entities to limit the use and disclosure of protected health information to specifically authorized situations, and requires covered entities to implement security measures to protect health information that they maintain in electronic form. Among other things, HITECH made HIPAA’s security standards directly applicable to business associates, independent contractors or agents of covered entities that receive or obtain protected health information in connection with providing a service on behalf of a covered entity. HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

In addition, certain states have also adopted data privacy and security laws and regulations, which govern the processing of health-related and other personal information. Such laws and regulations will be subject to interpretation by various courts and other governmental authorities, thus creating potentially complex compliance issues. For example, CCPA, imposes obligations on businesses that meet certain thresholds that process the personal information of California residents (including employees based in California). These obligations include, but are not limited to, providing specific disclosures in privacy notices and affording California residents certain rights related to their personal information, including the ability to opt-out of certain sales of personal information. The CCPA provides for a private right of action for certain data breaches, which may increase the likelihood of, and risks associated with, data breach litigation. Although the CCPA exempts some data processed in the context of clinical trials, the CCPA could increase compliance costs and potential liability. The 2020 amendments to the CCPA also created the California Privacy Protection Agency, a new enforcement agency whose sole responsibility is to enforce the CCPA and is empowered to create new CCPA regulations. Other states have also passed comprehensive privacy laws, and similar laws are being considered in several other states, as well as at the local and federal levels, including discussion in the U.S. of a new comprehensive federal data privacy law. In addition to government activity and private rights of actions provided by some of the state privacy laws, privacy advocacy groups and technology and other industries are considering various new, additional or different self-regulatory standards that may place additional burdens on companies.

Internationally, many countries have privacy and data protection laws that create potentially complex compliance issues . For example, the EU GDPR and UK GDPR impose strict requirements for processing the personal data of individuals, including, for example, requirements to establish a legal basis for processing, higher standards for obtaining consent from individuals to process their personal data, more robust disclosures to individuals and a strengthened individual data rights regime, requirements to implement safeguards to protect the security and confidentiality of personal data that requires the adoption of administrative, physical and technical safeguards, shortened timelines for data breach notifications to appropriate data protection authorities or data subjects, limitations on retention and secondary use of information, increased requirements pertaining to health data, regulation of the transferring of personal data across jurisdiction and additional obligations when third-party processors are contracted in connection

23

with the processing of the personal data. EU member states are tasked under the EU GDPR to enact, and have enacted, certain implementing legislation that adds to and/or further interprets the EU GDPR requirements and potentially extends the obligations and potential liability for failing to meet such obligations. Under the EU GDPR, government regulators may impose temporary or definitive bans on data processing, as well as fines of up to €20 million or 4% of annual global revenue, whichever is greater. Such fines would be in addition to (i) the rights of individuals to sue for damages in respect of any data privacy breach which causes them to suffer harm, (ii) the right of individual member states to impose additional sanctions over and above the administrative fines specified in the GDPR and (iii) the ability of supervisory authorities to impose orders requiring companies to modify their practices.

Additionally, the federal Physician Payments Sunshine Act within the ACA, and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) report annually to CMS information related to certain payments or other transfers of value made or distributed to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals and to report annually certain ownership and investment interests held by physicians and their immediate family members. Manufacturers are also required to report such information regarding its relationships with physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants and certified nurse midwives during the previous year.

Commercial distribution of products requires compliance with state laws that require the registration of manufacturers and wholesale distributors of drug in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state. Some states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution, including some states that require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain. In addition, several states have enacted legislation requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities, and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to pharmaceutical and biotechnology companies for use in sales and marketing, and to prohibit certain other sales and marketing practices. Certain local jurisdictions also require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures. Sales and marketing activities are also potentially subject to federal and state consumer protection and unfair competition laws.

Violation of any of the federal and state healthcare laws described above or any other governmental regulations may result in penalties, including without limitation, significant civil, criminal and/or administrative penalties, damages, fines, disgorgement, exclusion from participation in government programs, such as Medicare and Medicaid, imprisonment, injunctions, private “qui tam” actions brought by individual whistleblowers in the name of the government, refusal to enter into government contracts, oversight monitoring, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings.

Coverage, pricing and reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which regulatory approval is obtained. In the United States and markets in other countries, sales of any products for which regulatory approval is received for commercial sale will depend, in part, on the extent to which third-party payors provide coverage, and establish adequate reimbursement levels for such products. In the United States, third-party payors include federal and state healthcare programs, private managed care providers, health insurers and other organizations. The process for determining whether a third-party payor will provide coverage for a product may be separate from the process for setting the price of a product or for establishing the reimbursement rate that such a payor will pay for the product. Third-party payors may limit coverage to specific products on an approved list, also known as a formulary, which might not include all of the FDA-approved products for a particular indication. Third-party payors are increasingly challenging the price, examining the medical necessity and reviewing the cost-effectiveness of medical products, therapies and services, in addition to questioning their safety and efficacy. Expensive pharmaco-economic studies may need to be conducted in order to demonstrate the medical necessity and cost-effectiveness of product candidates, in addition to the costs required to obtain the FDA approvals. Product candidates may not be considered medically necessary or cost-effective. A payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. Further, one payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage for the product. Adequate third-party reimbursement may not be available to enable the maintenance of price levels sufficient to realize an appropriate return on investment in product development.

Different pricing and reimbursement schemes exist in other countries. In the EU, governments influence the price of pharmaceutical products through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of those products to consumers. Some jurisdictions operate positive and negative list systems under which products

24

may only be marketed once a reimbursement price has been agreed. To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that compare the cost-effectiveness of a particular product candidate to currently available therapies. Other member states allow companies to fix their own prices for medicines, but monitor and control company profits. The downward pressure on health care costs has become very intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country.

The marketability of any product candidates for which regulatory approval is received for commercial sale may suffer if the government and other third-party payors fail to provide coverage and adequate reimbursement. In addition, emphasis on managed care in the United States has increased and is expected to continue to increase the pressure on healthcare pricing. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which regulatory approval is received, less favorable coverage policies and reimbursement rates may be implemented in the future.

Healthcare reform

Healthcare reforms that have been adopted, and that may be adopted in the future, could result in further reductions in coverage and levels of reimbursement for pharmaceutical products, increases in rebates payable under U.S. government rebate programs and additional downward pressure on pharmaceutical product prices. Healthcare reform proposals recently culminated in the enactment of the Inflation Reduction Act, which eliminated, beginning in 2025, the coverage gap under Medicare Part D by significantly lowering the enrollee maximum out-of-pocket cost and requiring manufacturers to subsidize, through a newly established manufacturer discount program, 10% of Part D enrollees’ prescription costs for brand drugs below the out-of-pocket limit, and 20% once the out-of-pocket limit has been reached. The Inflation Reduction Act also allows HHS to directly negotiate the selling price of a statutorily specified number of drugs each year that CMS reimburses under Medicare Part B and Part D. The negotiated price may not exceed a statutory ceiling price. Only high-expenditure single-source drugs that have been approved for at least 7 years (11 years for biologics) can qualify for negotiation, with the negotiated price taking effect two years after the selection year. For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D drugs in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced. CMS has selected 15 additional Medicare Part D drugs for negotiated maximum fair pricing in 2027. For 2028, an additional 15 drugs, which may be covered under either Medicare Part B or Part D, will be selected, and for 2029 and subsequent years, 20 Part B or Part D drugs will be selected. A drug or biological product that has an orphan drug designation for only one rare disease or condition will be excluded from the Inflation Reduction Act’s price negotiation requirements, but loses that exclusion if it has designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation. The Inflation Reduction Act also imposes rebates on Medicare Part B and Part D drugs whose prices have increased at a rate greater than the rate of inflation. The Inflation Reduction Act permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years. Manufacturers that fail to comply with the Inflation Reduction Act may be subject to various penalties, some significant, including civil monetary penalties. The Inflation Reduction Act also extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025. These provisions have begun taking effect progressively starting in 2023, although they may be subject to legal challenges. For example, the provisions related to the negotiation of selling prices of high-expenditure single-source drugs and biologics have been challenged in multiple lawsuits. Thus, while it is unclear how the Inflation Reduction Act will be implemented, it will likely have a significant impact on the pharmaceutical industry and the pricing of pharmaceutical products, particularly pharmaceutical products indicated for prevalent conditions. The One Big Beautiful Bill Act, or OBBBA, which was recently signed into law, reduces funding to federal healthcare programs and imposes additional requirements to be eligible for healthcare, which may result in decreased access to healthcare, particularly for Medicaid programs. It is unclear to what extent other statutory, regulatory, and administrative initiatives will be enacted and implemented in the future.

Employees and human capital resources

As of December 31, 2025, we had 141 employees, all of whom were full-time and 108 of whom were engaged in research and development activities. Approximately 55 of our employees hold Ph.D. or M.D. degrees. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be an asset.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. It is important that we not only attract and retain the best and brightest diverse talent, but also ensure they remain engaged and can thrive in an environment that is committed to helping them grow, succeed and contribute directly to achieving our purpose. The principal purposes of our equity and cash incentive plans are to attract, retain and motivate personnel through the granting of stock-based and cash-based compensation awards in order to increase the success of our Company by motivating such individuals to perform to the best of their abilities in the furtherance of our objectives. We also strive to foster career growth and internal mobility by providing a broad range of training, mentoring and other development opportunities.

25

Corporate information

We were incorporated under the laws of the State of Delaware on August 29, 2017, originally under the name Genetic Modifiers NewCo, Inc. We changed our name on July 5, 2018 to Modulus Therapeutics, Inc. and on September 25, 2018, to Maze Therapeutics, Inc.

Our principal executive offices are located at 171 Oyster Point Blvd., Suite 300, South San Francisco, California 94080, and our telephone number is (650) 850-5070. Our website address is www.mazetx.com.

We file annual, quarterly and current reports, proxy statements and other documents with the Securities and Exchange Commission, or SEC, under the Securities Exchange Act. The SEC maintains an Internet website that contains reports, proxy and information statements, and other information regarding issuers, including us, that we file electronically with the SEC. The public can obtain any documents that we file with the SEC at www.sec.gov. Copies of each of our filings with the SEC can also be viewed and downloaded free of charge at our website, www.mazetx.com, after the reports and amendments are electronically filed with or furnished to the SEC.

Also available on our website is information relating to our corporate governance and our Board, including our Corporate Governance Guidelines; our Code of Business Conduct; and our Board Committee Charters. We will provide any of the foregoing information without charge upon written request to our Corporate Secretary.

We use our Investor Relations website (http://ir.mazetx.com) as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD promulgated by the SEC. These disclosures are included in the “news and events” section of our website. Accordingly, investors should monitor this portion of our website, in addition to following our press releases, SEC filings and public conference calls and webcasts.

The information contained on our website does not constitute, and shall not be deemed to constitute, a part of this Annual Report on Form 10-K, or any other report we file with, or furnish to, the SEC. Our references to the URLs for websites are intended to be inactive textual references only.

The mark “Maze Therapeutics,” the Maze logo, “Maze Compass” and all product names are our registered or common law trademarks. All other service marks, trademarks and trade names appearing in this Annual Report on Form 10-K are the property of their respective owners. Solely for convenience, the trademarks and tradenames referred to in this Annual Report on Form 10-K appear without the ® and ™ symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights, or the right of the applicable licensor to these trademarks and tradenames.