What changed in this filing

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Item 1. Business

2026-03-17 compared with 2025-03-13 · 199 added, 139 removed, 647 unchanged (34% of the section changed)

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Bryan Giraudo, our Chief Financial Officer and Chief Operating Officer, has extensive biotechnology and medical technology finance experience, having previously served as Senior Managing Director at Leerink Partners and Managing Director at Merrill Lynch, Pierce, Fenner & Smith Incorporated.

Richard Aranda, M.D., our Chief Medical Officer, is an experienced clinician and drug developer with previous experience at Bristol Myers Squibb Company, Novo-Nordisk, Inc., Receptos and Celegene Corporation.

Bob Smith, our Chief Commercial Officer, has over 30 years of experience in pharmaceuticals, with a strong focus on PAH and rare disease.

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Caryn Peterson, our Executive Vice President, Regulatory Affairs, has considerable experience and regulatory expertise as a Managing Director of Development & Strategic Consulting Associates, as well as management positions leading regulatory affairs at Syndax Pharmaceuticals and FeRx Incorporated.

We are a clinical-stage biopharmaceutical company focused on the development and commercialization of seralutinib for the treatment of PH.

Our goal is to be an industry leader in, and to enhance the lives of patients living with, PH.

Critical components of our business strategy include:

• Complete the ongoing Phase 3 PROSERA Study of seralutinib in PAH and pursue regulatory approval.

We commenced the registrational Phase 3 PROSERA Study in PAH in the fourth quarter of 2023.

We expect to report topline data from the PROSERA study in the fourth quarter of 2025.

If the clinical trial is successful, we will seek marketing approval for seralutinib in the United States.

• Increase the impact of seralutinib by expanding development into PH indications of high unmet need.

We believe that not only does seralutinib offer potential as a therapeutic option for the treatment of PAH but also for the treatment of other rare PH indications of high unmet need, including PH-ILD.

To that end, we expect to activate clinical sites for a global registrational Phase 3 for the treatment of PH-ILD in the second half of 2025.

Additionally, we will continue to evaluate other potential related indications of high unmet need for further development of seralutinib.

• Leverage the clinical development and commercialization expertise of our world-class team.

Our executive management team and key scientific leaders have successfully discovered, developed and commercialized pharmaceuticals at both large and small biopharmaceutical companies.

Additionally, we have built experienced PH development and commercialization teams, with key team members selected from the leadership of companies such as Actelion, Johnson & Johnson, Merck and United Therapeutics.

• Build our operational capabilities to successfully commercialize seralutinib for PH, if approved.

If we obtain regulatory approvals for seralutinib, we intend to build in-house sales and marketing capabilities to commercialize seralutinib in the United States, as part of our global collaboration and license agreement, or collaboration agreement, with Chiesi Farmaceutici S.p.A and Chiesi USA, Inc., or collectively, Chiesi.

Both PAH and PH-ILD patients are often treated by cardiologists and pulmonologists at national or regional centers of excellence.

These concentrations of patients could allow us to commercialize seralutinib with a relatively small commercial footprint, if approved.

Seralutinib (PDGFR, CSF1R and c-KIT Inhibitor)

Our near-term strategy is to focus our resources on advancing seralutinib for the treatment of PAH and to pursue regulatory alignment and potential approval as efficiently as possible.

Based on the totality of data from the Phase 3 PROSERA Study and the Phase 2 TORREY Study, including general consistency across endpoints and within higher risk subgroups, we believe seralutinib demonstrates a risk benefit profile that supports continued regulatory dialogue.

Following our February 2026 announcement of topline results from PROSERA, we are prioritizing (i) completing in-depth analyses of the PROSERA dataset, (ii) engaging with the U.S.

Food and Drug Administration, or FDA, to obtain feedback regarding potential regulatory paths forward, and (iii) evaluating our strategic options and resource allocation as a company, in addition to strengthening our capital structure.

The key elements of our near-term strategy include:

• Obtain FDA feedback and seek to define a regulatory path forward in PAH.

We are completing analyses of the PROSERA dataset and plan to engage with the FDA, including through requesting a Type C meeting, to understand their perspective on the totality of the PROSERA and TORREY datasets and potential regulatory paths forward.

• Advance preparations toward a potential NDA submission.

We are advancing NDA‑readiness activities and plan to engage with the FDA to clarify the appropriate regulatory path forward.

Our decision to submit an NDA, and the timing of any submission, will be informed by ongoing analyses of the PROSERA dataset, the totality of clinical data to date, and FDA feedback.

• Advance toward potential approval while maintaining disciplined resource allocation.

If an NDA is submitted and accepted for substantive review, the timing of any FDA action would depend on the applicable review timeline and other factors.

While timing remains subject to FDA feedback and other variables, we currently anticipate a potential approval action date by year end 2027.

• Continue ongoing open-label extension studies:

The open-label extension studies remain active, and continued follow‑up is intended to further characterize longer‑term exposure and potential durability of effect.

• Pause SERANATA enrollment while evaluating implications of PROSERA and next steps.

While we have paused SERANATA enrollment to support disciplined resource allocation and to evaluate the implications of PROSERA as we engage with regulators, we continue to believe seralutinib may have meaningful potential in fibrotic lung disease, including PH‑ILD, informed in part by the connective tissue disease-associated PAH, or CTD‑APAH, findings in PROSERA.

• Enhance our capital structure through proactive engagement with stakeholders.

This includes evaluating a range of potential alternatives related to our outstanding convertible notes to support our strategic priorities.

We may also seek to raise additional capital through equity offerings, debt financings or other capital sources to support our strategic priorities.

• Advance RT234 under our option agreement with Respira in a capital‑efficient manner.

We intend to continue advancing RT234 pursuant to our option agreement with Respira Therapeutics, which is structured to support limited foundational manufacturing and device readiness activities while preserving our focus and operational resources for seralutinib.

We believe RT234 represents a complementary, on‑demand therapeutic opportunity in PAH and PH‑ILD and could be ready to re‑enter clinical development as early as 2027.

Seralutinib (Inhaled PDGFR, CSF1R and c-KIT Inhibitor)

Seralutinib, also known as GB002, is an investigational inhaled, small molecule, platelet-derived growth factor receptor, or PDGFR, colony-stimulating factor 1 receptor, or CSF1R, and c-KIT inhibitor, currently being evaluated in a Phase 3 clinical trial for the treatment of PAH.

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Inhaled seralutinib, which is designed to act on both isoforms of the PDGFR, α and β, as well as the CSF1R and c-KIT pathways, inhibited and reversed cellular overgrowth in lung blood vessels in multiple animal PAH models.

In February 2026, we announced topline results from the 48-week Phase 3 PROSERA Trial in 390 PAH patients.

Seralutinib demonstrated a placebo-adjusted improvement in the primary endpoint, six-minute walk distance (6MWD) at Week 24, of 13.3 meters (p = 0.0320), missing the prespecified alpha threshold of 0.025.

At Week 24, in this well treated patient population, patients receiving seralutinib had a median change of 28.2 meters from baseline, while patients receiving placebo had a median change from baseline of 13.5 meters.

Consistent with the completed Phase 2 TORREY Study, seralutinib delivered a compelling signal in the prespecified intermediate‑ and high‑risk subgroup (n = 234), as defined by the REVEAL 2 Lite Risk Score ≥ 6 at screening, with a 20.0m placebo‑adjusted improvement in 6MWD (nominal p = 0.0207).

Three of four key secondary endpoints also demonstrated a nominal p-value below 0.0125 in this subpopulation, underscoring seralutinib’s activity in patients with higher risk.

Additional analyses are ongoing.

Additionally, we believe seralutinib may have meaningful potential in fibrotic lung disease, including PH‑ILD.

In PROSERA, the subgroup of patients with CTD-APAH (n = 87) demonstrated a placebo‑adjusted improvement in 6MWD at Week 24 of 37.0 meters (nominal p = 0.0104).

We believe the biology of connective tissue disease‑associated PAH may be relevant to broader fibrotic lung disease populations, including PH-ILD.

CTD APAH has historically been associated with poorer outcomes and less clinical response to PAH therapies compared with idiopathic PAH, and patients may experience higher rates of treatment related adverse events that can limit therapy options.

We activated clinical sites and began screening patients for the SERANATA Phase 3 study in PH‑ILD, but following our February 2026 announcement of topline results from PROSERA, we paused enrollment in SERANATA to allow for further evaluation of the PROSERA dataset, including regional variability, and to support disciplined resource allocation as we engage with regulators regarding potential paths forward.

In December 2022, we announced positive topline results from the 24-week Phase 2 TORREY trial in 86 PAH patients.

In this well-treated patient population, the seralutinib arm demonstrated a statistically significant, placebo-adjusted improvement of 14.3% in its primary efficacy endpoint, pulmonary vascular resistance, or PVR.

Seralutinib has been generally well tolerated in all completed clinical trials.

We dosed the first patient in our registrational Phase 3 PROSERA Study in PAH in the fourth quarter of 2023.

We expect to report topline data from the PROSERA study in the fourth quarter of 2025.

In addition to PAH, we believe that seralutinib holds potential as a therapeutic option for the treatment of PH-ILD, and to that end, we expect to activate clinical sites for a global registrational Phase 3 for the treatment of PH-ILD in the second half of 2025.

In the pre-specified elevated-risk subgroup (REVEAL 2.0 Risk Score ≥ 6), seralutinib showed notable improvements at Week 24 compared to placebo, including a 21.9-meter increase in 6-minute walk distance (6MWD;

nominal p = 0.2482), a 23% reduction in

pulmonary vascular resistance (PVR;

nominal p = 0.0134), and a 732 ng/L decrease in NT-proBNP levels (nominal p = 0.0002).

We are completing analyses of the PROSERA dataset and plan to engage with the FDA, including through requesting a Type C meeting, to understand their perspective on the PROSERA and TORREY datasets and potential regulatory paths forward.

Across the Phase 2 TORREY and Phase 3 PROSERA studies, we believe that the totality of evidence supports that seralutinib has been generally well tolerated in PAH in heavily treated populations.

In May 2024, we entered into a collaboration agreement with Chiesi.

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We in-licensed seralutinib from Pulmokine, Inc.

The United States Food and Drug Administration, or FDA, the European Commission, or EC, and the Pharmaceuticals and Medical Devices Agency, or PMDA, of Japan have granted seralutinib orphan drug designation for the treatment of patients with PAH.

The following table summarizes the current development plan for seralutinib in PH:

The FDA, the European Commission, or EC, and the Pharmaceuticals and Medical Devices Agency, or PMDA, of Japan have granted seralutinib orphan drug designation for the treatment of patients with PAH.

Chiesi is currently evaluating the totality of the PROSERA dataset.

Mechanism of Action in PAH

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Macrophages, which express the CSF1 receptor, are now recognized to play an important role in PAH pathology.

Activated CSF1R positive macrophages accumulate around pulmonary arterioles in PAH, which have been shown in vivo in PAH patients with positron emission tomography.

Activated CSF1R positive macrophages accumulate around pulmonary arterioles in PAH, which have been

shown in vivo in PAH patients with positron emission tomography.

Additionally, macrophage activity in PAH is associated with bone morphogenetic protein receptor type II, or BMPR2, levels.

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The true incidence and prevalence of PAH are unknown.

The estimated PAH patient population in the US is about 50,000 patients, and the estimated patient population in the EU is over 70,000 patients.

The estimated PAH patient population in the US is about 50,000 patients, and the estimated patient population in the European Union, or EU, is over 70,000 patients.

The number of diagnosed PAH patients continues to increase, and we believe this increase is likely due to enhanced awareness and diagnosis of the disease.

Worldwide branded drug sales for PAH and PH-ILD therapies totaled over $7 billion in 2023.

Worldwide branded drug sales for therapies used in PAH and PH ILD represent a multi-billion dollar global market.

Treatment Paradigm in PAH

Currently approved PAH therapies consist of three classes of vasodilators and one activin ligand trap therapy.

The three classes of vasodilatory therapy are PDE5 inhibitors (and guanylate cyclase stimulators), ERAs, and prostanoids (and prostacyclin receptor agonists).

The three classes of vasodilatory therapy are phosphodiesterase type 5, or PDE5, inhibitors (and guanylate cyclase stimulators), ERAs, and prostanoids (and prostacyclin receptor agonists).

PDE5 inhibitors are often used in combination with ERAs as an early treatment strategy.

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We believe that seralutinib has potential as a therapeutic treatment for PH-ILD, a subtype of WHO Group 3 Pulmonary Hypertension.

PH-ILD is a collection of progressive and often fatal forms of PH that affect the small airways of the

PH-ILD is a collection of progressive and often fatal forms of PH that affect the small airways of the lungs.

PH-ILD includes PH related to idiopathic pulmonary fibrosis and PH related connective tissue disease-associated interstitial lung disease, amongst other diseases.

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Patients living with PH-ILD generally have a poor disease prognosis and have an increased mortality rate, as compared to PAH patients.

We believe seralutinib may have potential in fibrotic lung disease, including PH‑ILD.

In PROSERA, the subgroup of patients with CTD‑APAH demonstrated a placebo‑adjusted improvement in 6MWD at Week 24 of 37.0 meters (nominal p=0.0104).

We believe the biology of connective tissue disease‑associated disease may be relevant to broader fibrotic lung disease populations, including PH‑ILD.

There is only one FDA-approved treatment for PH-ILD, and there are no approved therapies in the EU.

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Summary of Preclinical Program

Seralutinib inhibits both PGDFR α and β, and it inhibited and reversed cell overgrowth in lung blood vessels in a PAH rat model, which replicates many features of human PAH, including the abnormal cell proliferation that can block the small vessels of the lung.

Seralutinib inhibits both PDGFR α and β, and it inhibited and reversed cell overgrowth in lung blood vessels in a PAH rat model, which replicates many features of human PAH, including the abnormal cell proliferation that can block the small vessels of the lung.

Seralutinib substantially reduced the occlusive lesions in the small lung blood vessels in this model.

Additionally, seralutinib demonstrated a statistically significant reduction in right ventricular systolic pressure as compared to placebo.

In a separate rat model of PAH, the SU5416 hypoxia model, seralutinib demonstrated a statistically significant reduction in circulating plasma NT-proBNP as compared to placebo, while the difference between imatinib and placebo was not significant for this PAH biomarker.

Seralutinib also restored rat lung BMPR2 expression to healthy levels, which was a statistically significant improvement as compared to placebo and imatinib.

Irregularities in BMPR2 expression have been linked to PAH.

significant for this PAH biomarker.

Seralutinib also restored rat lung BMPR2 expression to healthy levels, which was a statistically significant improvement as compared to placebo and imatinib.

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There were no SAEs, and the most frequently reported AEs were mild-to-moderate cough and mild headache.

Systemic PK was characterized by low systemic exposure and rapid drug clearance in PAH patients, which was consistent with PK data from the Phase 1a studies in healthy

Systemic PK was characterized by low systemic exposure and rapid drug clearance in PAH patients, which was consistent with PK data from the Phase 1a studies in healthy volunteers.

Target engagement in PAH patients was demonstrated via whole blood CSF1R stabilization assay across all tested dose levels.

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No cases of subdural hematoma were reported in the study.

Summary of Ongoing TORREY Open-Label Extension Clinical Trial in PAH

Upon completion of the 24-week blinded portion of the Phase 2 TORREY Study, 73 of the 80 (91%) completing patients elected to rollover into an ongoing open-label extension trial.

In the TORREY open-label continued-seralutinib group treated for 72 weeks continued improvement was noted in PVR and 6MWD, as compared to TORREY baseline.

Consistent with completed clinical trials, seralutinib has been generally well tolerated as of December 31, 2024, in the ongoing open-label extension study.

Summary of Ongoing PROSERA Phase 3 PAH Clinical Trial

In the fourth quarter of 2023, we commenced the registrational Phase 3 PROSERA Study, a randomized, double-blind, placebo-controlled, global clinical trial in PAH patients, after receiving input from global regulatory authorities, including the FDA and European Medicines Agency, or EMA.

We are enrolling approximately 350 Functional Class II and III PAH patients on stable background therapy.

Patients will be randomized in a 1:1 fashion to 90 mg twice daily seralutinib or placebo, and patients will receive blinded therapy for up to 48 weeks.

Patients will remain on their background PAH therapies throughout the trial.

The primary endpoint of the PROSERA trial is change from baseline in 6MWD at Week 24.

A key secondary endpoint is time to first clinical worsening while on blinded therapy, up to 48 weeks.

In addition to secondary and exploratory endpoints, safety and tolerability will also be evaluated in the Phase 3 PROSERA Study.

We expect to report topline data from the PROSERA study in the fourth quarter of 2025.

If the clinical trial is successful, we will seek marketing approval for seralutinib in the United States.

Summary of Planned Phase 3 Clinical Trial in PH-ILD

We expect to activate clinical sites for a global registrational Phase 3 for the treatment of PH-ILD in the second half of 2025.

The planned Phase 3 clinical trial will be a registrational, randomized, double-blind, placebo-controlled, global clinical trial in PH-ILD patients.

We have discussed the protocol design with global regulatory authorities and this will inform the final design of the Phase 3 clinical trial.

The primary endpoint of the trial will be change in 6MWD from baseline.

In the TORREY open‑label extension (OLE), participants who continued on seralutinib demonstrated continued improvement in PVR through later follow‑up, with median PVR decreasing from 620 dyne·s/cm⁵ at baseline to 505 at Week 24 and 475 at Week 72.

These OLE findings are descriptive and provide additional longer‑term context beyond the 24‑week blinded period.

Summary of Completed Phase 3 PAH Clinical Trial (PROSERA Study)

PROSERA was a randomized, double‑blind, placebo‑controlled, global Phase 3 study in patients with WHO Functional Class II and III PAH on background therapy, randomized 1:1 to seralutinib or placebo and treated for up to 48 weeks.

The primary endpoint was change from baseline in 6MWD at Week 24 in the intent‑to‑treat population, with key secondary endpoints including time to clinical worsening, clinical improvement, change in NT‑proBNP, and reduction in REVEAL Lite 2 risk score.

In February 2026, we announced topline results from PROSERA.

At Week 24, seralutinib demonstrated a placebo adjusted improvement in 6MWD of 13.3 meters versus placebo (p = 0.0320), which did not meet the prespecified statistical alpha threshold of 0.025.

At Week 24, patients receiving seralutinib had a median change in 6MWD from baseline of 28.2 meters, compared with 13.5 meters for patients receiving placebo.

A key secondary endpoint, change in NT‑proBNP at Week 24, demonstrated an estimated location shift of ‑120.4 ng/L compared with placebo (nominal p = 0.0002) in the overall population, with separation between the arms favoring seralutinib observed starting at Week 4 (-96.0 ng/L;

nominal p = 0.0002).

Key secondary endpoints time-to-clinical worsening (TTCW), clinical improvement and proportion of patients with a one point or greater reduction in REVEAL Lite 2 Risk Score all favored seralutinib as compared to placebo in the overall population.

In a prespecified subgroup analysis of patients with REVEAL Lite 2 score ≥6 at screening, corresponding to intermediate- and high-risk patients, seralutinib demonstrated a potentially clinically meaningful response profile across the primary and key secondary endpoints.

All key secondary endpoints favored seralutinib, with placebo‑adjusted effects including NT‑proBNP at Week 24 (location shift = -265.8 ng/L;

nominal p = 0.0002), ≥1‑point improvement in REVEAL Lite 2 risk score at Week 24 (odds ratio = 2.033;

nominal p = 0.0083), clinical improvement at Week 24 (odds ratio = 3.318;

nominal p = 0.0101), and TTCW through Week 48 (hazard ratio = 0.744;

nominal p = 0.4360).

Notably, in patients with CTD‑APAH, seralutinib demonstrated an improvement in six‑minute walk distance, achieving a placebo‑adjusted gain of 37.0 meters at Week 24 (n = 87;

nominal p = 0.0104), indicating a potentially strong clinically meaningful treatment effect in this clinically challenging subgroup.

We continue to interrogate our computed tomography (CT) functional respiratory imaging (FRI) exploratory substudy data.

Given the exploratory nature of the technology, we are taking the appropriate steps to understand the totality of the data and the utility of the technology.

Overall, seralutinib was generally well tolerated in the PROSERA Study.

TEAEs were reported in 86.5% of patients receiving seralutinib and 80.5% of patients receiving placebo.

Treatment-emergent SAEs occurred in 16.0% of patients receiving seralutinib and 18.9% of patients receiving placebo.

Transaminase elevations of three times or greater of the upper limit of normal were observed in 13% of patients receiving seralutinib and 1% of patients receiving placebo.

In seralutinib treated patients, liver enzyme elevations tended to occur early in treatment, and generally resolved with drug interruption or discontinuation, with rapid recovery reported in observed cases.

The most frequently reported adverse event in patients treated with seralutinib was cough, reported in 37.0% of patients.

Summary of Ongoing Open-Label Extensions (Phase 1b, Phase 2 & Phase 3)

Patients from the Phase 1b study, the Phase 2 TORREY Study, and the Phase 3 PROSERA Study continue in ongoing open‑label extension studies of seralutinib, where we are monitoring longer‑term safety and tolerability and where we are further characterizing the durability of clinical response.

Summary of Paused SERANATA Phase 3 Clinical Trial in PH-ILD

Starting in the fourth quarter of 2025, we activated clinical sites and began screening patients for the SERANATA Phase 3 study in PH‑ILD.

Following our February 2026 announcement of topline results from PROSERA, we paused enrollment in SERANATA to allow for further evaluation of the PROSERA dataset, including regional variability, and to support disciplined resource allocation as we engage with regulators regarding potential paths forward.

RT234 (Inhaled, On‑Demand PDE5 Inhibitor)

RT234 is an investigational inhaled, as‑needed, or PRN, dry‑powder formulation of vardenafil, a PDE5 inhibitor, being developed for PAH and PH‑ILD.

PDE5 inhibitors are an established class with multiple approved oral therapies for chronic use in PAH;

however, there are no approved inhaled PDE5 therapies and no approved PRN treatments designed for on‑demand symptom relief in PAH or PH‑ILD.

Oral vardenafil is approved for erectile dysfunction.

PRN use refers to administration at the time of need, rather than on a scheduled, chronic dosing regimen, with the objective of providing rapid symptom relief.

In September 2025, we entered into an option agreement with Respira Therapeutics to acquire RT234.

RT234 has completed open‑label Phase 2 clinical trials and is intended to address an unmet need for on‑demand symptom management that may complement existing chronic PH therapies.

Current activities by Respira Therapeutics are focused on foundational manufacturing and device readiness, and subject to those ongoing activities, RT234 could reenter clinical development as early as 2027.

See Note 14 to our consolidated financial statements included elsewhere in this annual report for additional details regarding the Respira option agreement.

The biotechnology and pharmaceutical industries are characterized by rapid technological advancement, significant competition and an emphasis on intellectual property.

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We believe that the key competitive factors affecting the success of any of our product candidates will include efficacy, safety profile, convenience, cost, level of promotional activity devoted to them and intellectual property protection.

We expect to face competition for seralutinib from existing products and products in development.

We expect to face competition for seralutinib and RT234 from existing products and products in development.

Seralutinib is a PDGFR, CSF1R and c-KIT inhibitor initially targeted for PAH and PH-ILD patients.

We expect competition within the PAH indication will include prostanoids / prostacyclin receptor agonists, including Orenitram (United Therapeutics), Uptravi (Janssen), Tyvaso (United Therapeutics), and Remodulin (United Therapeutics), and activin ligand traps, including Winrevair (Merck).

We also may face some competition from products used in Functional Class I and II patients, such as the oral PDE5 inhibitors, including Revatio (Pfizer Inc.) and Adcirca (United Therapeutics);

We expect competition within the PAH indication will include prostanoids / prostacyclin receptor agonists, including Orenitram (United Therapeutics), Uptravi (Janssen), Tyvaso (United Therapeutics), Yutrepia (Liquidia) and Remodulin (United Therapeutics), and activin ligand traps, including Winrevair (Merck).

We also may face some competition from products used as frontline therapy for PAH, such as the oral PDE5 inhibitors, including Revatio (Pfizer Inc.) and Adcirca (United Therapeutics);

the sGC stimulator Adempas (Bayer AG);

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We believe that, if approved, seralutinib could be used alongside all classes of approved therapies.

PAH is also an active indication for investigational drugs, and we may face competition in the future from CS1 (Cereno Scientific), L606 (Liquidia / Pharmosa Biopharm Inc.), treprostinil palmitil (Insmed), ralinepag (United Therapeutics), and REGN13335 (Regeneron Pharmaceuticals, Inc.).

Additionally, although not approved for the treatment of PAH, we may face competition from formulations of imatinib, including the one in development from Tenax Therapeutics and Inhibikase Therapeutics.

We expect to face competition from Tyvaso (United Therapeutics) within the PH-ILD indication, as it is the only approved therapy for PH-ILD in the United States.

PAH is also an active indication for investigational drugs, and we may face competition in the future from L606 (Liquidia / Pharmosa Biopharma Inc.), CS1 (Cereno Scientific), treprostinil palmitil inhalation powder (Insmed, Inc.), ralinepag (United Therapeutics), REGN13335 (Regeneron), HS235 (35Pharma, Inc.), LTP001 (Novartis), APL‑9796 (Apollo Therapeutics Ltd), and ROC‑101 (AllRock Bio, Inc.).

Additionally, although not approved for the treatment of PAH, we may face competition from formulations of imatinib, including the one in

development from Inhibikase Therapeutics.

While there are multiple classes of therapies with marketing approval for PAH, there are currently no therapies approved for PRN use to provide rapid, on‑demand symptom relief.

We expect to face competition from Tyvaso (United Therapeutics) and Yutrepia (Liquidia) within the PH-ILD indication, as they are the only approved therapies for PH-ILD in the United States.

There are no approved therapies for PH-ILD in the EU.

PH-ILD is also an active indication for investigational drugs, and we may face competition in the future from L606 (Liquidia / Pharmosa Biopharm Inc.), sirolimus (OrphAI Therapeutics), treprostinil palmitil (Insmed, Inc.), MK-5475 (Merck), and mosliciguat (Pulmovant, Inc.).

PH-ILD is also an active indication for investigational drugs, and we may face competition in the future from L606 (Liquidia / Pharmosa Biopharma Inc.), sirolimus (OrphAI Therapeutics), treprostinil palmitil inhalation powder (Insmed, Inc.), mosliciguat (Pulmovant, Inc.), mirivadelgat (ForeSee Pharmaceuticals Co., Ltd.), APL‑9796 (Apollo Therapeutics Ltd), and ROC‑101 (AllRock Bio, Inc.).

While there is one class of therapy with marketing approval for PH-ILD, there are currently no therapies approved for PRN use to provide rapid, on‑demand symptom relief.

There may be other earlier stage clinical programs that, if approved, would compete with seralutinib.

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In the ROW Territory, Chiesi will pay us an escalating mid-to-high teens percentage royalty, subject to standard deductions, on net sales of Licensed Product for PAH and additional indications on a Licensed Product-by-Licensed Product and country-by-country basis with such payment obligations beginning on the first commercial sale of Licensed Product in such country and expiring on a country-by-country basis on the latest of (a) the expiration of a valid claim to our patent right in such country, (b) the expiration of regulatory exclusivity, and (c) the date that is 10 years after the first commercial sale of such Licensed Product in such country.

In addition, we granted to Chiesi an option to purchase directly from us, on one or more occasions, up to an aggregate number of shares of our common stock such that immediately following such issuance, Chiesi’s beneficial ownership of our common stock shall not exceed 9.9% of the total number of issued and outstanding shares of our common stock, or the Equity Option.

The Equity Option shall be exercisable by Chiesi, in whole or in part, at any time prior to the earliest to occur of the date on which (a) the last patient is last dosed in either (i) the PROSERA Phase 3 study for PAH or (ii) a Phase 3 clinical trial for the PH-ILD Indication, (b) any third party commences a tender offer or exchange offer for more than 50% of the outstanding shares of our common stock, and (c) we publicly announces our intent to consummate a GB002 change of control.

The purchase price of each share of our common stock subject to the Equity Option shall be equal to 107.5% of the daily volume-weighted average per share price of our common stock on The Nasdaq Stock Market over the 30-trading day period ending on and including the last trading day prior to the date on which Chiesi delivers an exercise notice to us;

provided that such purchase price shall be no less than $1.63 per share.

The shares of our common stock to be issued will be issued in a private placement in reliance on Section 4(a)(2) of the Securities Act of 1933, as amended, for transactions by an issuer not involving any public offering, pursuant to the terms of a stock issuance agreement to be entered into between us and Chiesi in connection with each such exercise of the Equity Option.

Unless earlier terminated, the collaboration agreement will remain in force until no Licensed Products are being developed or commercialized in the United States and in the ROW Territory, on a country-by-country basis, until no royalty terms are in effect for all countries.

royalty terms are in effect for all countries.

Either party may terminate the collaboration agreement for the other party’s material breach, subject to a specified notice and cure periods, or due to an insolvency event of the other party.

In lieu of termination upon a party’s material breach due to non-payment of development costs within a specified time the non-breaching party may elect an alternative remedy which may involve modifications to their performance and payment obligations.

We have the right to terminate by providing written notice in the event Chiesi or its affiliates or sublicensee brings a patent challenge and Chiesi

does not take certain steps to withdraw from or cease supporting such challenge.

We have the right to terminate by providing written notice in the event Chiesi or its affiliates or sublicensee brings a patent challenge and Chiesi does not take certain steps to withdraw from or cease supporting such challenge.

Chiesi may terminate the collaboration agreement for any reason upon prior written notice to us, subject to a notice period.

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If marketed individually, each component would be subject to different regulatory pathways and reviewed by different centers within the FDA.

A combination product, however, is assigned to a Center that will have primary jurisdiction over its regulation based on a determination of the combination product’s primary mode of action, which is the single mode of action that provides the most important therapeutic action.

single mode of action that provides the most important therapeutic action.

In the case of seralutinib, the primary mode of action is attributable to the drug component of the product, which means that the FDA’s Center for Drug Evaluation and Research has primary jurisdiction over the premarket development, review and approval.

Accordingly, we plan to investigate seralutinib through the Investigational New Drug, or IND, framework and seek approval through the NDA pathway.

We do not anticipate

that the FDA will require a separate medical device authorization for the device, but this could change during the course of its review of any marketing application that we may submit.

We do not anticipate that the FDA will require a separate medical device authorization for the device, but this could change during the course of its review of any marketing application that we may submit.

Drug Development Process

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All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCP regulations, which among other things, include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial.

Clinical Trials must be conducted under protocols

detailing, among other things, the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated.

Clinical Trials must be conducted under protocols detailing, among other things, the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated.

Each protocol must be submitted to the FDA as part of the IND as well as any subsequent protocol amendments.

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Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug.

In addition, appropriate packaging must be

selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

The manufacturing process must be capable of

consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug.

In addition, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Regulation of Combination Products in the United States

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The resubmitted application also is subject to review before the FDA accepts it for filing.

Once filed, the FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity,

strength, quality and purity.

Under the Prescription Drug User Fee Act, or PDUFA, guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA for a new molecular entity to review and act on the submission.

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Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or inability to manufacture the product in sufficient quantities.

The designation of such drug also entitles a party to financial incentives such

as opportunities for grant funding toward clinical trial costs, tax advantages and user-fee waivers.

disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or inability to manufacture the product in sufficient quantities.

The designation of such drug also entitles a party to financial incentives such as opportunities for grant funding toward clinical trial costs, tax advantages and user-fee waivers.

However, competitors, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.

In addition, if an orphan designated product receives marketing approval for a disease or condition broader than what is designated, it may not be entitled to orphan exclusivity.

In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if the second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if the second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity within the relevant approved use or indication or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs relating to the approved use or indication of patients with the rare disease or condition.

Expedited Development and Review Programs

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Pediatric exclusivity provides for an additional six months of marketing exclusivity attached to an existing period of regulatory exclusivity or patent term if a sponsor conducts clinical trials in children in response to a written request from the FDA.

issuance of a written request does not require the sponsor to undertake the described clinical trials.

The issuance of a written request does not require the sponsor to undertake the described clinical trials.

In addition, orphan drug exclusivity, as described above, may offer a seven-year period of marketing exclusivity, except in certain circumstances.

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In order to obtain coverage and reimbursement for any product that might be approved for marketing, we may need to conduct expensive studies in order to demonstrate the medical necessity and cost-effectiveness of any products, which would be in addition to the costs expended to obtain regulatory approvals.

Third-party payors may not consider seralutinib to be medically necessary or cost-effective compared to other available therapies, or the rebate percentages required to secure favorable coverage may not yield an adequate margin over cost or may not enable us to maintain price levels sufficient to realize an appropriate return on our investment in drug development.

Healthcare Reform

In the United States, there has been, and continues to be, several legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of product candidates, restrict or regulate post-approval activities, and affect the profitable sale of product candidates.

Among policy makers and payors in the United States, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access.

In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.

In March 2010, the Patient Protection and Affordable Care Act, or ACA, was passed, which substantially changed the way healthcare is financed by both the government and private insurers, and significantly impacts the U.S.

pharmaceutical industry.

The ACA, among other things:

(1) increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations;

(2) created a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for certain drugs and biologics that are inhaled, infused, instilled, implanted or injected;

(3) established an annual, nondeductible fee on any entity that manufactures or imports certain specified branded prescription drugs and biologic agents apportioned among these entities according to their market share in certain government healthcare programs;

(4) expanded the availability of lower pricing under the 340B drug pricing program by adding new entities to the program;

(5) expanded the eligibility criteria for Medicaid programs;

(6) created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research;

(7) established a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research;

and (8) established a Center for Medicare and Medicaid Innovation at the Centers for Medicare & Medicaid Services, or CMS, to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drugs.

In the United States and some foreign jurisdictions, there has been, and we expect there will continue to be, several legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of product candidates, restrict or regulate post-approval activities, and affect the profitable sale of product candidates.

Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access.

In the United States and elsewhere, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative and regulatory initiatives.

We expect that current laws and regulations, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and additional downward pressure on the price that we may receive for seralutinib.

In particular, there have been and continue to be a number of initiatives at the U.S.

federal and state levels that seek to reduce healthcare costs and improve the quality of healthcare.

For example, in 2010, the ACA was enacted in the United States.

Among the provisions of the ACA of importance to seralutinib, the ACA:

established an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents;

extended manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;

established a new Patient-Centered Outcomes Research Institute to oversee, and established a Center for Medicare and Medicaid Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.

Since its enactment, there have been judicial and political challenges to certain aspects of the ACA.

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Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

Other legislative changes have been proposed and adopted since the ACA was enacted.

On August 2, 2011, the Budget Control Act of 2011 was signed into law, which, among other things, resulted in aggregate reductions of Medicare payments to providers, which went into effect on April 1, 2013 and, due to subsequent legislative amendments to the statute,

will remain in effect through 2032, with the exception of a temporary suspension from May 1, 2020 through March 31, 2022, unless additional Congressional action is taken.

On January 2, 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, reduced Medicare payments to several providers, including hospitals, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

On March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap, beginning January 1, 2024.

The rebate was previously capped at 100% of a drug’s average manufacturer price.

Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products.

Most recently, on August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap;

Further, there has been heightened governmental scrutiny in the United States of pharmaceutical pricing practices in light of the rising cost of prescription drugs.

Such scrutiny has resulted in several recent congressional inquiries and

proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.

The Inflation Reduction Act, or IRA, was enacted in 2022.

This statute marks the most significant action by Congress with respect to the pharmaceutical industry since adoption of the ACA in 2010.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023);

and replaces the Part D coverage gap discount program with a new manufacturer discounting program (which began in 2025).

The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

CMS has published the negotiated prices for the initial ten drugs, which will first be effective in 2026, and has published the list of the subsequent 15 drugs that will be subject to negotiation, although the Medicare drug price negotiation program is currently subject to legal challenges.

For that and other reasons, it is currently unclear how the IRA will be effectuated.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure, drug price reporting and other transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Some states have enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states.

redesigns the Medicare Part D benefit (beginning in 2024);

and replaces the Part D coverage gap discount program with a new manufacturer discount program (beginning in 2025).

CMS has published the negotiated prices for the initial ten drugs, which became effective in 2026, and the subsequent 15 drugs, which will first be effective in 2027.

CMS has also published the next set of 15 drugs that will be subject to negotiation.

The IRA permits the Secretary of the Department of Health and Human Services (HHS) to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

HHS has and will continue to issue and update guidance as these programs are implemented, although the Medicare drug price negotiation program is currently subject to legal challenges.

The impact of the IRA on us and the pharmaceutical industry cannot yet be fully determined, but is likely to be significant.

In addition, the One Big Beautiful Bill Act, which was enacted in July 2025, imposes significant reductions in the funding of the Medicaid program.

Such reductions are expected to decrease the number of persons enrolled in Medicaid and reduce the services covered by Medicaid, which could adversely affect our ability to generate revenue, attain profitability or commercialize seralutinib.

Furthermore, the Trump administration is pursuing a two-fold strategy to reduce drug costs in the U.S.

While it is unclear whether and how the Trump proposals will be implemented, the Trump policies are likely to have a negative impact on the pharmaceutical industry and on our ability to receive adequate revenues for seralutinib.

On the one hand, President Trump has threatened to impose significant tariffs on pharmaceutical manufacturers that do not adopt pricing policies such as most favored nation pricing, which would tie the price for drugs in the U.S.

to the lowest price in a group of other countries.

In response, multiple manufacturers have reportedly entered into confidential pricing agreements with the federal government.

On the other hand, the Trump administration is pursuing traditional regulatory pathways to impose drug pricing policies, and published two proposed regulations in December 2025, referred to as Globe and Guard.

If finalized, these regulations would implement mandatory payment models under which manufacturers of eligible drugs would be required to pay rebates to the federal government on a portion of the units of their drugs that are reimbursed by Medicare, with the rebate amount based on most favored nation pricing.

Imposing a rebate in the U.S.

that is based on drug prices outside the U.S.

would mark a drastic and unprecedented shift in the U.S.

pharmaceutical market, and while the impact of the Globe and Guard proposed regulations, if finalized, cannot yet be determined, it is likely to be significant.

Even regulatory proposals or executive actions that are ultimately deemed unlawful could negatively impact the U.S.

pharmaceutical sector and our business.

In addition, pharmaceutical pricing and marketing has long been the subject of considerable discussion in Congress and among policymakers, and it is possible that Congress could enact additional laws that negatively affect the pharmaceutical industry.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure, drug price reporting and other transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Some states have enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states, and at least one state board is imposing an upper payment limit.

States are also seeking to implement general, across the board price caps for pharmaceuticals, or are seeking to regulate drug distribution.

Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations, financial condition and prospects.

In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

This could reduce the ultimate demand for seralutinib, if approved, or put pressure on our product pricing, which could negatively affect our business, results of operations, financial condition and prospects.

In the EU, similar political, economic and regulatory developments may affect our or Chiesi's ability to profitably commercialize, or co-commercialize, seralutinib, if approved.

For instance, on December 13, 2021, Regulation No 2021/2282 on Health Technology Assessment, or HTA, amending Directive 2011/24/EU, was adopted.

The Regulation entered into force in January 2022 and has been applicable since January 2025, with phased implementation based on the type of product, i.e.

oncology and advanced therapy medicinal products as of 2025, orphan medicinal products as of 2028, and all other medicinal products by 2030.

The Regulation intends to boost cooperation among EU member states in assessing health

technologies, including new medicinal products, and provide the basis for cooperation at the EU level for joint clinical assessments in these areas.

It will permit EU member states to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the highest potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.

Individual EU member states will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement.

We expect that healthcare reform measures that may be adopted in the future may result in more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for any approved product.

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Similar to the federal Anti-Kickback Statute, A person or entity does not need to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician providers including physician assistants and nurse practitioners, and teaching hospitals, and applicable manufacturers and applicable group

purchasing organizations to report annually to CMS ownership and investment interests held by physicians (as defined by statute) and their immediate family members.

Similar state, local and foreign laws and regulations may also restrict business practices in the biopharmaceutical industry, such as state anti-kickback and false claims laws, which may apply to business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, or by patients themselves;

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For instance, in the EU, many EU member states have adopted specific anti-gift statutes that further limit commercial practices for medicinal products, in particular vis-à-vis healthcare professionals and organizations.

Additionally, there has been a recent trend of increased regulation of payments and transfers of value provided to healthcare professionals or entities and many EU member states have adopted national “Sunshine Acts” which impose reporting and transparency requirements (often on an annual basis), similar to the requirements in the United States, on pharmaceutical companies.

Additionally, there has been a recent trend of increased regulation of payments and transfers of value provided to healthcare professionals or

entities and many EU member states have adopted national “Sunshine Acts” which impose reporting and transparency requirements (often on an annual basis), similar to the requirements in the United States, on pharmaceutical companies.

Certain countries also mandate implementation of commercial compliance programs, or require disclosure of marketing expenditures and pricing information.

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Whether or not we obtain FDA approval for a product, we would need to obtain the necessary approvals by the comparable foreign regulatory authorities before we can commence clinical trials or marketing of the product in foreign countries and jurisdictions.

Although many of the issues discussed above with respect to the United States apply similarly in the context of the European Union, or EU, the approval process varies between countries and jurisdictions and can involve additional product testing and additional administrative review periods.

Although many of the issues discussed above with respect to the United States apply similarly in the context of EU, the approval process varies between countries and jurisdictions and can involve additional product testing and additional administrative review periods.

The time required to obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval.

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Certain countries outside of the United States have a similar process that requires the submission of a clinical trial application, or CTA, much like the IND prior to the commencement of human clinical trials.

Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use, or ICH, guidelines on GCP as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If the sponsor of the clinical trial is not established within the EU, it must appoint an EU entity to act as its legal representative.

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The centralized procedure is mandatory for certain types of products, such as:

(i) medicinal products derived from biotechnology medicinal

products, (ii) designated orphan medicinal products, (iii) advanced therapy medicinal products, or ATMPs, and (iv) medicinal products containing a new active substance indicated for the treatment certain diseases, such as HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto-immune and other dysfunctions and viral diseases.

(i) medicinal products derived from biotechnology medicinal products, (ii) designated orphan medicinal products, (iii) advanced therapy medicinal products, or ATMPs, and (iv) medicinal products containing a new active substance indicated for the treatment certain diseases, such as HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto-immune and other dysfunctions and viral diseases.

The centralized procedure is optional for products containing a new active substance not yet authorized in the EU, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU.

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In the EU, new products authorized for marketing, or reference products, generally receive eight years of data exclusivity and an additional two years of market exclusivity upon MA.

If granted, the data exclusivity period prevents generic or biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar MA in the EU during a period of eight years from the date on which the reference

product was first authorized in the EU.

During the additional two‑year period of market exclusivity, a generic or biosimilar MAA can be submitted, and the innovator’s data may be referenced, but no generic or biosimilar product can be marketed until 10 years have elapsed from the initial MA of the reference product in the EU.

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Pediatric development

In the EU, MAAs for new medicinal products have to include the results of trials conducted in the pediatric population, in compliance with a pediatric investigation plan, or PIP, agreed with the EMA’s Pediatric Committee, or PDCO.

In the EU, MAAs for new medicinal product candidates have to include the results of trials conducted in the pediatric population, in compliance with a pediatric investigation plan, or PIP, agreed with the EMA’s Pediatric Committee, or PDCO.

The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the product candidate for which MA is being sought.

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Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when these data is not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients.

Once the MA is obtained in all EU member states and study results are included in the product information, even when negative, the product is eligible for six months’ supplementary protection certificate extension (if any is in effect at the time of approval) or, in the case of orphan medicinal products, a two year extension of the orphan market exclusivity is granted.

Once the MA is obtained in all EU member states and study results are included in the product

information, even when negative, the product is eligible for six months’ supplementary protection certificate extension (if any is in effect at the time of approval) or, in the case of orphan medicinal products, a two year extension of the orphan market exclusivity is granted.

Orphan designation

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Similar to the United States, both MA holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the EC and/or the competent regulatory authorities of the member states.

The holder of a MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance, or QPPV, who is responsible for establishment and maintenance of that system, and oversees the safety

profiles of medicinal products and any emerging safety concerns.

Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.

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The aforementioned EU rules are generally applicable in the European Economic Area, or EEA, which consists of the 27 EU member states plus Norway, Liechtenstein and Iceland.

Failure to comply with EU and member state laws that apply to the conduct of clinical trials, manufacturing approval, MA of medicinal products and marketing of such products, both before and after grant of the MA, manufacturing of pharmaceutical products, statutory health insurance, bribery and anti-corruption or with other applicable regulatory requirements may result in administrative, civil or criminal penalties.

requirements may result in administrative, civil or criminal penalties.

These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

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Since the end of the Brexit transition period on January 1, 2021, and the implementation of the Windsor Framework on January 1, 2025, the United Kingdom, or UK, has not generally been directly subject to EU laws with respect to medicinal products.

It is currently unclear to what extent the government of the UK will seek to align its regulations with the EU.

The EU laws that have been transposed into UK law through secondary legislation remain applicable in Great Britain (England, Scotland and Wales), or GB, however, new legislation such as the (EU) CTR is not applicable in GB.

Whilst the EU-UK Trade and Cooperation Agreement, or TCA, includes the mutual recognition of GMP inspections of manufacturing facilities for medicinal products and GMP documents issued, it does not contain wholesale mutual recognition of UK and EU pharmaceutical regulations and product standards.

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broadly, Northern Ireland continued to follow the EU regulatory regime.

However, on January 1, 2025, a new arrangement called the “Windsor Framework” came into effect and reintegrated Northern Ireland under the regulatory authority of the MHRA with respect to medicinal products.

The Windsor Framework removes EU licensing processes, and EU labelling and serialization requirements in relation to Northern Ireland, and introduces a UK-wide licensing process for medicinal products.

However, on January 1, 2025, an arrangement called the “Windsor Framework” came into effect and reintegrated Northern Ireland under the regulatory authority of the MHRA with respect to medicinal products.

The Windsor Framework removes EU licensing

processes, and EU labelling and serialization requirements in relation to Northern Ireland, and introduces a UK-wide licensing process for medicinal products.

MAs in the UK are governed by the Human Medicines Regulations (SI 2012/1916), as amended.

All existing EU MAs for centrally authorized products were automatically converted or grandfathered into UK MAs, effective in GB (only), free of charge on January 1, 2021, unless the MA holder opted-out.

Under the terms of the Windsor Framework, these MAs became valid for the whole of the UK from January 1, 2025.

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The UK regulatory framework in relation to clinical trials is derived from the now-repealed EU Clinical Trials Directive (as implemented into UK law, through the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended).

The extent to which the regulation of clinical trials in the UK will mirror the (EU) CTR in the long term is not yet certain, however, on December 12, 2024, the UK government introduced a legislative proposal - the Medicines for Human Use (Clinical Trials) Amendment Regulations 2024 - that, if implemented, will replace the current regulatory framework for clinical trials in the UK.

The legislative proposal aims to provide a more flexible regime to make it easier to conduct clinical trials in the UK, increase the transparency of clinical trials conducted in the UK and make clinical trials more patient centered.

The UK government has provided the legislative proposal to the UK Parliament for its review and approval.

Once the legislative proposal is approved (with or without amendment), it will be adopted into UK law which is expected in early 2026.

In April 2025, the UK government introduced the Medicines for Human Use (Clinical Trials) Amendment Regulations 2024.

The amendment, which will take effect from April 2026, aims to provide a more flexible regime to make it easier to conduct clinical trials in the UK, increase the transparency of clinical trials conducted in the UK and make clinical trials more patient centered.

Foreign Data Privacy and Security Laws

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business