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Item 1. Business

2026-03-11 compared with 2025-03-03 · 136 added, 186 removed, 410 unchanged (44% of the section changed)

We are a late-stage biopharmaceutical company focused on discovering and developing novel therapies for the treatment of fibrosis and related diseases.

Our initial focus is on treating fibrosis by inhibiting integrin-mediated activation of TGF-β.

We have applied our deep understanding of fibrosis biology, along with our medicinal chemistry and translational medicine expertise to develop a set of proprietary tools designed to discover and de-risk product candidates quickly and efficiently.

Our wholly owned lead product candidate, bexotegrast, is an oral, small molecule, dual selective inhibitor of αvβ6 and αvβ1 integrins.

We have recently discontinued BEACON-IPF trial, a global Phase 2b trial in patients with idiopathic pulmonary fibrosis (IPF).

While an imbalance in unadjudicated IPF-related adverse events between the treatment and placebo groups led to the discontinuation of the trial, early evidence of efficacy on the forced vital capacity (FVC) endpoint was also observed.

The Company plans to analyze the complete data from the BEACON-IPF trial and evaluate next steps for bexotegrast’s development.

Our second clinical program, PLN-101095, is a small molecule, dual selective inhibitor of integrins αvβ8 and αvβ1 for the treatment of solid tumors that are resistant to immune checkpoint inhibitors.

We are currently enrolling the fourth of five dose cohorts in a Phase 1 open-label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors.

Preliminary data from cohorts one through three is expected in the first quarter of 2025.

Our Phase 1-ready program PLN-101325, is in development for treatment of muscular dystrophies, including Duchenne muscular dystrophy.

PLN-101325 is a monoclonal antibody designed to act as an allosteric agonist of integrin α7β1.

PLN-101325 has received a clinical trial approval (CTA) in Australia.

Our Lead Candidate - Bexotegrast

Our lead wholly owned product candidate, bexotegrast, is an oral, small molecule, dual-selective inhibitor of αvß6 and αvß1.

While expressed at very low levels in normal tissues, αvß6 and αvß1 are upregulated in the pulmonary tissues of IPF patients.

They both serve as activators of TGF-β, leading to increased collagen production and fibrosis in these tissues.

By blocking TGF-β activation by both αvß6 and αvß1, we believe bexotegrast may slow and potentially halt the progression of fibrosis in these patient populations.

Bexotegrast has been granted orphan drug designation by the FDA, and the European Medicines Agency, or EMA, and Fast Track designation by the FDA for IPF.

Bexotegrast for Treatment of IPF

IPF is the most common and severe form of progressive pulmonary fibrosis, affecting approximately 150,000 patients in the United States and over 3 million patients around the world.

While the underlying cause of IPF is unknown, the course of the disease is well documented, with progressive scarring that destroys the structure and function of the lungs over time.

The average life expectancy for patients with confirmed IPF is between three and five years.

There are currently two FDA-approved therapies for IPF.

Both have shown modest slowing of disease progression.

However, both therapies have safety and tolerability challenges that lead to treatment interruption, dose adjustment, and permanent discontinuation.

Bexotegrast is an oral small molecule that selectively inhibits both αvß6 and αvß1 integrins that we are developing as a potential therapy for IPF and PSC.

It has been shown that expression of both αvß6 on epithelial cells and αvß1 on fibroblasts can lead to excessive activation of TGF-β in fibrosis.

Epithelial tissue includes any tissue that lines the surfaces of the body such as alveoli, bile ducts, urinary tract, skin, and gastrointestinal tract.

Each of these tissues contains multiple cell types including epithelial cells and fibroblasts.

An important secondary effect of the TGF-β cascade is that it promotes upregulation of αvß6 on epithelial cells and αvß1 on fibroblasts.

The increased expression of these integrins on the cell surface contributes in turn to further TGF-β activation in a TGF-β-driven positive feed-forward loop.

In May 2023, we announced final data from INTEGRIS-IPF, a multinational, randomized, double-blind, placebo-controlled Phase 2a clinical trial of bexotegrast in patients with IPF.

The trial compared bexotegrast doses of 40 mg, 80 mg, 160 mg and 320 mg versus placebo over 12 weeks of treatment, with the 320 mg dose group allowed to treat for at least 24 weeks.

The trial met its primary and secondary endpoints demonstrating that bexotegrast was well tolerated over a 12-week treatment period and displayed a favorable pharmacokinetic profile.

The trial’s exploratory efficacy endpoints assessing changes in forced vital capacity, or FVC, Quantitative Lung Fibrosis, or QLF, imaging, serum biomarkers and clinical symptoms.

Bexotegrast demonstrated a dose-dependent treatment effect on FVC, FVC percent predicted, or FVCpp, and QLF, as well as serum biomarkers and cough compared to placebo over 12 weeks in treated patients.

Bexotegrast was well tolerated over 12 weeks of treatment with no drug related serious adverse events, or SAEs.

Bexotegrast at 320 mg demonstrated a statistically significant mean increase in FVC from baseline at all timepoints up to 12 weeks, surpassing all lower dose groups, and showed a strong treatment effect on FVC, FVCpp, QLF, profibrotic biomarkers and cough versus placebo at 12 weeks.

The bexotegrast 320 mg group also met its primary and secondary endpoints at 24 weeks, demonstrating that bexotegrast was well tolerated over the 24-week treatment period and displayed a favorable pharmacokinetic profile.

At Week 24, bexotegrast at 320 mg, in combination with standard of care, reduced FVC decline by 80% relative to standard of care alone.

Eighty-nine percent of bexotegrast-treated patients who experienced an increase in FVC from baseline at Week 12 maintained an increase at Week 24.

Bexotegrast at 320 mg showed a strong treatment effect with stabilization of fibrosis as measured by QLF imaging at Week 24.

Bexotegrast was well tolerated up to 40 weeks of treatment at 320 mg with no drug-related serious adverse events.

In August 2023, we initiated BEACON-IPF, a 52-week, multinational, randomized, dose-ranging, double-blind, placebo-controlled Phase 2b trial evaluating bexotegrast at doses of 160 mg or 320 mg at sites in the United States.

In March 2024, we initiated the Phase 2b/3 adaptive portion of the BEACON-IPF trial at global sites outside of the U.S.

The BEACON-IPF Phase 2b portion of this multinational trial is enrolling approximately 360 patients with IPF.

The primary endpoint is an assessment of the change from baseline in absolute mL of forced vital capacity (FVC) at Week 52.

Key secondary endpoints include the measurement of time to disease progression (defined as either a ≥10% decline from baseline in FVC precent predicted (FVCpp), respiratory-related hospitalization, or all-cause mortality), change from baseline of absolute FVC (mL) with or without background therapies, change from baseline in patient reported measurements of symptoms, well-being at Week 52 and safety and tolerability.

On March 3, 2025, we announced that, following a prespecified data review and recommendation by the trial’s independent DSMB, as well as a secondary review and recommendation by an outside expert panel, Pliant has discontinued the BEACON-IPF Phase 2b trial.

We are a clinical-stage biopharmaceutical company focused on discovering and developing integrin-based therapeutics.

Our lead program is focused on the development of treatments for solid tumors by inhibiting integrin-mediated activation of transforming growth factor-β (TGF-β).

We have applied our deep understanding of integrin biology, along with our medicinal chemistry and translational medicine expertise to develop a proprietary drug discovery platform that we believe has broad applicability across multiple areas of disease.

Our wholly owned lead product candidate, PLN-101095, is an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins in development for the treatment of solid tumors.

In 2025, we announced positive data from a Phase 1 open-label dose-escalation trial of PLN-101095 as monotherapy and in combination with the immunotherapy pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors.

We also continue to explore the full potential of our drug discovery platform consisting of a proprietary library of over 15,000 integrin binding molecules, focusing on integrin-based target-mediated drug delivery.

Our Lead Candidate - PLN-101095 for Treatment of Solid Tumors That are Resistant to Immune Checkpoint Inhibitors

Our lead wholly owned product candidate, PLN-101095, is an oral, small molecule dual inhibitor of αvß8 and αvß1 integrins for the treatment of solid tumors that are resistant to immune checkpoint inhibitors, or ICIs.

As TGF-β biology has been elucidated, it has become increasingly understood in the scientific literature that TGF-β plays an important anti-inflammatory role in the tumor micro-environment, preventing T-cell infiltration and inhibiting release of various cytokines.

This mechanism is becoming increasingly recognized as a potential cause of the resistance to checkpoint inhibitors such as anti-PD-1 therapies seen in many tumors.

We are targeting the TGF-β activating integrins αvβ8 and αvβ1, which are upregulated in certain tumors, with the goal of sensitizing tumors to checkpoint inhibitors.

In March 2025 and December 2025, we announced positive data from a Phase 1 open label dose-escalation trial of PLN-101095.

In this trial PLN-101095 was administered as monotherapy for 14 days, followed by combination therapy with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors.

In this heavily pretreated patient population, PLN-101095 demonstrated anti-tumor activity in combination with pembrolizumab.

Across the three highest dose cohorts, there were four responders consisting of one confirmed complete response (CR) and three partial responses (PR) (two confirmed, one unconfirmed) out of the 10 secondary ICI refractory patients.

Clinical responses were observed in patients with cholangiocarcinoma, melanoma, head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC).

The median time on treatment in these patients was 15 months as of November 30 th , 2025.

Sixty percent of secondary refractory patients demonstrated stable disease or tumor reduction.

Sixteen patients with nine different tumor types were enrolled in five cohorts.

Patients were treated for 14 days with PLN-101095 monotherapy administered orally at doses of 250 mg twice a day (BID) (n=1), 500 mg BID (n=2), 1000 mg

BID (n=6), 1000 mg three times a day (TID) (n=4) or 2000 mg BID (n=3), followed by the addition of pembrolizumab at 200 mg administered intravenously every three weeks.

All responding patients showed large increases (4- to 13-fold vs.

baseline) in plasma interferon gamma (IFN-γ) after a 14-day run-in period of monotherapy with PLN-101095.

No non-responders showed meaningful increases in IFN- γ.

PLN-101095 was generally well tolerated across all doses tested with few discontinuations (n=2) due to adverse events.

PLN-101095 demonstrated a dose-dependent pharmacokinetic profile.

Based on the response data, coupled with the supportive IFN- γ biomarker data, Pliant plans to accelerate the development of PLN-101095 with the initiation of a Phase 1b indication expansion trial assessing NSCLC and other tumor types with strong mechanistic rationale for integrin inhibition in 2026.

Proprietary Platform Supports Early-Stage Programs

Since our founding, we have built a drug discovery platform that today consists of a proprietary library of over 15,000 integrin binding molecules, utilizing a comprehensive screening assay system (binding, integrin confirmation, ligand-induced internalization) and an advanced live human tissue program.

We believe our library holds tremendous potential to serve as the basis for integrin-based drug delivery by utilizing tissue-specific integrin receptors.

Pliant has utilized the library to develop a platform capable of delivering drug payloads including siRNAs to selective cell types.

Current programs are focused on delivering siRNAs to skeletal muscle cells, adipocytes, and renal cells.

We believe this platform potentially has broad applicability across multiple disease areas utilizing a variety of drug payloads.

Bexotegrast Discontinued in the Development of IPF and PSC

Bexotegrast is an oral, small molecule, dual-selective inhibitor of αvß6 and αvß1 that was in development for the potential treatment of idiopathic pulmonary fibrosis (IPF) as part of the 52 week Phase 2b BEACON-IPF trial and the treatment of primary sclerosing cholangitis (PSC) as part of the 12 week Phase 2a INTEGRIS-PSC trial.

On March 3, 2025, we announced that, following a prespecified data review and recommendation by the BEACON-IPF independent DSMB, as well as a secondary review and recommendation by an outside expert panel, Pliant has discontinued the Phase 2b trial.

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In comparison, the IPF-related adverse event rate in pooled placebo group of the INTEGRIS-IPF study was 10% with a comparable treatment duration to that of BEACON-IPF (mean exposure duration approximately 16 weeks).

The Company plans to analyze the complete data from the BEACON-IPF trial and evaluate next steps for bexotegrast’s development.

Once the full analysis is completed, which should provide a better understanding of the benefit risk profile and therapeutic window of bexotegrast, the Company will consider additional dose-ranging Phase 2b studies with lower doses in pulmonary fibrosis and potentially other, non-respiratory indications, including liver diseases.

Bexotegrast for Treatment of Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis, or PSC is a progressive liver disorder affecting approximately 30,000 to 45,000 patients in the United States.

The disease is characterized by fibrosis originating in the bile ducts that ultimately results in bile flow obstruction or cholestasis, causing liver inflammation and progressive fibrosis of the liver.

Patients have a median

survival of 10 to 12 years without intervention and carry high lifetime risk of developing gastrointestinal malignancies.

There are currently no FDA-approved therapies for PSC.

We conducted and have announced results from INTEGRIS-PSC, a Phase 2a trial of bexotegrast in PSC.

The trial compared bexotegrast doses of 40 mg, 80 mg, 160 mg and 320 mg versus placebo over 12-weeks of treatment, with the 320 mg dose cohort allowed to treat for at least 24 weeks.

Results from the INTEGRIS-PSC trial were positive with data disclosed in company press releases in 2023 and 2024.

We have discontinued the development of bexotegrast in IPF.

We conducted and have announced results from INTEGRIS-PSC with positive results disclosed in company press releases in 2023 and 2024.

Following discussions with regulatory authorities, it is clear that a cost effective and efficient development path for Pliant in PSC is not available at this time;

however, we continue to evaluate the best path forward for this program.

PLN-101095 for Treatment of Solid Tumors That are Resistant to Immune Checkpoint Inhibitors

Our third clinical program to date, PLN-101095, is an oral, dual inhibitor of αvß8 and αvß1 integrins for the treatment of solid tumors with a suboptimal response to immune checkpoint inhibitors, or ICIs.

This mechanism is becoming increasingly recognized as a potential cause of the resistance to checkpoint inhibitors such as anti-PD-1 therapies seen in many tumors.

We are targeting the TGF-β activating integrins αvβ8 and αvβ1, which are upregulated in certain tumors, with the goal of sensitizing tumors to checkpoint inhibitors.

We are currently dosing the fourth of five planned dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy for 14 days, followed by combination therapy with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors.

Preliminary data from first three cohorts of the Phase 1 trial are expected in the first quarter of 2025.

PLN-101325 for Treatment of Muscular Dystrophies

We are developing PLN-101325, a monoclonal antibody targeting α7β1 for treatment of muscular dystrophies, including Duchenne Muscular Dystrophy, or DMD.

The α7β1 integrin is upregulated on muscle cells in several muscular dystrophy indications.

It partially compensates for the lack of dystrophin by helping to anchor muscle cells to the extracellular matrix.

PLN-101325 binds and allosterically activates α7β1 in order to augment this naturally occurring compensatory mechanism.

Because the antibody is not mutation specific, it could potentially be effective as a single therapy or in combination with other treatment modalities across multiple muscular dystrophy indications.

A clinical trial approval (CTA) was granted in Australia and is active in authorizing the initiation of a Phase 1 clinical trial of PLN-101325 in healthy volunteers .

We have assembled an executive team with highly relevant experience in fibrosis, small molecule drug discovery and clinical development.

We have assembled an executive team with highly relevant experience in, small molecule drug discovery and clinical development.

Bernard Coulie, M.D., Ph.D., our President and Chief Executive Officer, has over 20 years of experience in drug development, previously serving as Chief Executive Officer and Chief Medical Officer of ActoGeniX, as well as holding senior roles at Johnson & Johnson.

Éric Lefebvre, M.D., our Chief Medical Officer, brings deep experience in clinical development in liver disease.

He previously served as head of clinical research and development for the MASH program at Allergan.

Prior to Allergan, Dr.

Lefebvre led HIV and HCV development at Janssen and later served as Chief Medical Officer at Tobira.

Our science builds on the research of world-renowned researchers Dean Sheppard, M.D., Rik Derynck, Ph.D., Bill DeGrado, Ph.D.

and Hal Chapman, M.D., all from the University of California, San Francisco, who bring broad experience in fibrosis biology and small molecule chemistry among other related disciplines.

Our goal is to become a world-leading fibrosis company, developing and commercializing disease- modifying therapies across a spectrum of fibrotic diseases.

Minnie Kuo, our Chief Operating Officer, has over 20 years of multinational clinical development experience across various therapeutic areas including oncology as operational officer at Vir Biotechnology and multiple therapeutic areas while holding senior clinical roles at Gilead Sciences and Nektar Therapeutics.

Our goal is to become a leading integrin-drug development company, developing and commercializing disease- modifying therapies across a spectrum of diseases.

To achieve this, we are focused on the following key strategies:

• Rapidly advance bexotegrast through clinical development and commercialization in IPF.

We are developing our lead oral, small molecule inhibitor of αvß6 and αvß1 as a novel therapy for IPF, an area of high unmet medical need.

IPF is an orphan indication that we believe we can commercialize on our own in key geographies using a targeted sales force.

• Selectively evaluate additional partnerships in indications and geographies where we believe partners can add significant commercial and/or development capabilities.

Fibrotic diseases represent a broad set of disease indications to pursue.

Our focus is to commercialize our assets in orphan fibrosis indications and to selectively work with partners in larger indications and in geographies outside of North America.

Furthermore, we will evaluate and potentially choose to partner our unpartnered product candidates in indications outside of fibrosis.

• Explore opportunities for our pipeline assets in additional fibrotic indications.

We are evaluating the potential benefit of our product candidates outside of their lead indications.

Our product candidates have shown anti-fibrotic activity in multiple animal models as well as human tissue in indications outside of IPF, PSC and MASH.

We will continue to evaluate additional indications to maximize the potential of our pipeline.

• Leverage our industry leading tools and capabilities to advance our mission of becoming a leading fibrosis company.

• Efficiently advance PLN-101095 through early clinical development and determine potential future indications.

We are developing our lead oral, small molecule inhibitor of αvß8 and αvß1 as a novel therapy for patients with solid tumors resistant to ICIs, an area of high unmet medical need.

• Selectively evaluate additional partnerships where we believe partners can add significant commercial and/or development capabilities.

Oncology drug development has the potential to represent a broad set of specific tumor type disease indications to pursue.

Our focus is to advance the program, assess the activity and determine what indication could best suited for commercialization by us and to selectively work with partners in larger indications and in geographies outside of North America.

Furthermore, we will evaluate and potentially choose to partner our product candidates.

• Explore opportunities to expand our pipeline in the areas of immunology and inflammation and oncology.

We evaluate external opportunities that leverage our expertise and enhance our portfolio with the goal of creating value for patients and shareholders.

• Leverage our proprietary library, screening tools and capabilities to advance our mission of becoming a leading integrin drug development company.

Since our founding, we have endeavored to advance the understanding of fibrosis biology, uncover new targets and advance novel product candidates.

Currently, our proprietary capabilities include a target expression atlas, an expansive library of over 10,000 integrin binding molecules, an integrin screening assay platform, a live fibrotic human tissue program, a PET-ligand imaging program and biomarker assays.

We continue to expand our integrin inhibitor library and develop tools such as additional PET-ligands as well as novel disease biomarkers.

In addition, we have a library of over 70,000 compounds for non-integrin targets.

We intend to leverage these tools and capabilities in a target- and modality-agnostic manner to expand our pipeline with a mission to become a world-leading fibrosis company.

Currently, our proprietary capabilities include an expansive library of over 15,000 integrin binding molecules, a comprehensive screening assay system (binding, integrin confirmation, ligand-induced internalization) and an advanced live human tissue program.

We continue to expand our integrin inhibitor library expand our pipeline with a mission to become a world- leading integrin drug development company.

The biotechnology and biopharmaceutical industries are characterized by rapidly advancing technologies, strong competition and an emphasis on proprietary products.

While we believe that our technology, knowledge, experience and scientific personnel provide us with competitive advantages, we face substantial competition from many different sources, including larger pharmaceutical companies with greater resources.

Smaller specialty biotechnology and biopharmaceutical companies, academic research institutions, governmental agencies, as well as public and private institutions are also potential sources of competitive products and technologies, including through collaborative arrangements with large and established biopharmaceutical companies.

While we believe that our technology, knowledge, experience and scientific personnel provide us with competitive advantages, we face substantial competition from multiple sources, including large and specialty pharmaceutical and biotechnology companies, academic research institutions and governmental agencies and public and private research institutions.

Our competitors compete with us on the level of technologies employed, or on the level of development of product candidates.

In addition, many small biotechnology companies have formed collaborations with large, established companies to (i) obtain support for their research, development and commercialization of products or (ii) combine several treatment approaches to develop longer lasting or more efficacious treatments that may potentially directly compete with our current or future product candidates.

We anticipate that we will continue to face increasing competition as new therapies and combinations thereof, technologies and data emerge within the field of oncology and, furthermore, within the treatment of solid tumors that have progressed on checkpoint inhibitors.

We also face competition in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and enrolling patients for clinical trials, and acquiring technologies complementary to, or necessary for, our programs.

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

There are a number of biopharmaceutical and biotechnology companies that are currently pursuing the development of products for the treatment of fibrosis.

Companies that we are aware of that are targeting the treatment of various fibrosis indications through inhibiting various parts of the TGF-β pathway include companies with significant financial resources such as AbbVie Inc., AstraZeneca plc, Bristol Myers Squibb Co., Corbus Pharmaceutical, Merck & Co., Inc., Novartis AG, Scholar Rock, Inc.

and Takeda Pharmaceutical Company.

Boehringer Ingelheim's PDE4B inhibitor (BI 1015550), Bristol Myers Squibb Co.’s LPAR1 inhibitor (BMS-986278) and United Therapeutics Corporation prostacyclin vasodilator (treprostinil) are the most advanced development candidates for the treatment of IPF.

Although our novel approach is unique from most other existing or investigational therapies across the disease areas where we are focusing our development, we will need to compete with currently approved therapies, and potentially those currently in development if they are approved.

We are aware of several marketed and investigational products in our leading disease areas, including but not limited to:

There are currently two approved products for the treatment of IPF;

pirfenidone – brand name Esbriet ® , marketed by Roche Holding AG, with generics marketed by Sandoz Group AG, Teva Pharmaceutical Industries Ltd., and others, and nintedanib – brand name Ofev ® , marketed by Boehringer Ingelheim GmbH.

Companies currently developing product candidates in IPF include Boehringer Ingelheim Pharmaceuticals, Inc., Bristol Myers Squibb Co., United Therapeutics Corporation, Amgen, Roche Holding AG, Vicore Pharma Holding, CSL Behring, PureTech Health PLC, GlaxoSmithKline, InSilico Medicines, Tvardi Therapeutics, BridgeBio Therapeutics Inc., Syndax Pharmaceuticals Inc., Endeavor BioMedicines, Inc., Contineum Therapeutics, Inc.and Avalyn Pharma Inc.

There are currently no approved therapies for the treatment of PSC.

Companies currently developing product candidates in PSC include Dr.

Falk Pharma GmbH, Mirum Pharmaceuticals, Inc., Chemomab Therapeutics Ltd., Ipsen Biopharmaceuticals Inc., Curome Biosciences and NGM Biopharmaceuticals, Inc.

The availability of reimbursement from government and other third-party payors will also significantly affect the pricing and competitiveness of our product candidates, if approved for marketing.

Our competitors also may obtain FDA or

other regulatory approval for their products more rapidly than we do, which could result in our competitors establishing a strong market position before we are able to enter the market.

In addition to the current standard of care treatments for patients with solid tumors who have progressed on checkpoint inhibitors, numerous commercial and academic preclinical studies and clinical trials are being undertaken by a large number of parties to assess novel technologies, product candidates, and combinations.

Companies that compete with us directly on the level of commercialization or development of product candidates targeting various parts of the TGF-β pathway include companies with significant financial resources such as AbbVie Inc., Bicara Therapeutics, CatalyM, Corbus Pharmaceuticals, Incyte Corporation, IO Biotech, Keros Therapeutics, Oncotelic Therapeutics, Pfizer, Roche/Genetech, Scholar Rock, and Sirnaomics.

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

If our product candidates do not offer sustainable advantages over other available products, we may not be able to successfully compete against current and future competitors.

Our competitors also may obtain FDA or other regulatory approval for their products more rapidly, resulting in a stronger or dominant market position before we are able to enter the market.

The key competitive factors affecting the success of all of our programs, if approved, are likely to be product safety, efficacy, convenience and treatment cost.

Intellectual Property

We strive to protect and enhance the proprietary technology, inventions, and improvements that are commercially important to the development of our business, including seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties.

We also rely on trade secrets relating to our proprietary technology platform and on know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen, and maintain our proprietary position in the field of fibrosis that may be important for the development of our business.

We also rely on trade secrets relating to our proprietary technology platform and on know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen, and maintain our proprietary position in the field of integrin-based therapeutics that may be important for the development of our business.

We additionally may rely on regulatory protection afforded through data exclusivity, market exclusivity, and patent term extensions, where available.

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With respect to both licensed and company-owned intellectual property, we cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our commercial products and methods of manufacturing the same.

As of February 26, 2025, we own or co-own over 300 pending patent applications worldwide in over 30 patent families, including United States and corresponding foreign patent applications.

As of February 26, 2025, thirteen U.S.

patents and thirty-nine foreign patents have been issued, granted or allowed.

Our patents and any patents that may issue from our pending patent applications are generally expected to expire between the years 2037 to 2046, subject to possible patent term adjustment and/or extension.

Company Owned IP

As of March 1, 2026, we own or co-own over 300 pending patent applications worldwide in over 30 patent families, including United States and corresponding foreign patent applications.

As of March 1, 2026, fourteen U.S.

patents and forty-four foreign patents have been issued, granted or allowed.

Our patents and any patents that may issue from our

pending patent applications are generally expected to expire between the years 2037 to 2047, subject to possible patent term adjustment and/or extension.

Our policy is to file patent applications to protect technology, inventions and improvements to inventions that are commercially important to the development of our business.

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We are a party to various other license agreements that give us rights to use specific technologies in our research and development.

Company Owned IP

We own multiple families of patent applications that are directed to small molecule compositions capable of modulating integrins and methods for treating or preventing diseases associated with integrins.

Certain applications in these families relate to our bexotegrast and PLN-1474 small molecule product candidates, backup compounds and structural analogs, various unit dosages, dosing regimens, and routes of administration.

We are also pursuing innovative ways to modulate integrin function using antibodies, and as of February 26, 2025 we have 35 pending patent applications to that technology in the United States and foreign jurisdictions.

As of February 26, 2025, we have one U.S.

Certain applications in these families relate to small molecule product candidates, backup compounds and structural analogs, various unit dosages, dosing regimens, and routes of administration.

We are also pursuing innovative ways to modulate integrin function using antibodies.

As of March 1, 2026, this antibody subset of our patent portfolio includes thirty-four pending patent applications in the United States and foreign jurisdictions.

As of March 1, 2026, this antibody subset of our patent portfolio includes one U.S.

patent and two foreign patents that have been issued, granted, or allowed.

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Trademark Protection

We have two registered U.S.

trademarks for use in connection with our products.

We have one registered U.S.

trademark for use in connection with our products.

We may pursue additional registrations for future products in markets of interest.

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Manufacturing

Our lead product candidate, bexotegrast, is a small molecule inhibitor amenable to standard formulation technologies.

Our lead product candidate, PLN-101095, is an oral small molecule inhibitor amenable to standard formulation technologies.

We have confirmed the utility of the synthetic process and manufactured multi-kilogram quantities sufficient to provide drug product for our clinical trials.

The manufacturing process of the drug substance for such product candidate is robust and accessed from readily available starting materials.

The synthetic route is amenable to large-scale production and does not require unusual equipment or handling during the manufacturing process.

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We also rely on internal personnel with extensive cGMP manufacturing experience in order to ensure effective technology transfer and to manage the manufacturing and development processes conducted by third-party manufacturers.

We have established an adequate supply of the drug substance for bexotegrast from our Asian contract manufacturing organizations, or CMOs, to satisfy both our clinical and preclinical requirements.

We are establishing an adequate supply of the drug substance for PLN-101095 from our Asian contract manufacturing organizations, or CMOs, to satisfy both our clinical and preclinical requirements.

As our development programs expand and we build new process efficiencies, we expect to continually evaluate this strategy with the objective of satisfying demand for our clinical trials and, if approved, the manufacture, sale, and distribution of commercial products.

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Department of Health and Human Services Office of the Inspector General, or HHS-OIG and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing, sale and distribution of drugs, such as those we are developing.

These agencies and other federal, state, and local entities regulate, among other things, the research and development, testing, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, approval, advertising and promotion, distribution, post-approval monitoring and reporting, sampling, coverage, reimbursement, pricing, and export and import of our product candidates.

These agencies and other federal,

state, and local entities regulate, among other things, the research and development, testing, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, approval, advertising and promotion, distribution, post-approval monitoring and reporting, sampling, coverage, reimbursement, pricing, and export and import of our product candidates.

government regulation of drug products

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Furthermore, the FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk.

an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.

Marketing approval

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Once the submission is accepted for filing, the FDA begins an in-depth substantive review.

The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.

The FDA reviews an NDA to determine,

among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.

The FDA may refer an application for a novel drug to an advisory committee.

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The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.

After approval, some types of changes to the approved product, such as adding

new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.

After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Fast Track designation

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Among these programs is Fast Track designation.

In May 2014, the FDA published a final Guidance for Industry titled “Expedited Programs for Serious Conditions Drugs and Biologics,” which provides guidance on the FDA programs that are intended to facilitate and expedite development and review of new drug or biological product candidates as well as threshold criteria generally applicable to concluding that a product candidate is a candidate for these expedited development and review programs.

The FDA published guidance on the FDA programs that are intended to facilitate and expedite development and review of new drug or biological product candidates as well as threshold criteria generally applicable to concluding that a product candidate is a candidate for these expedited development and review programs.

The FDA may designate a product for Fast Track review if it is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life-threatening disease or condition, and nonclinical or clinical data demonstrate the potential to address unmet medical needs for such a disease or condition.

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Moreover, 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, Congress is considering updates to the orphan drug provisions of the FDCA in response to a recent decision by the U.S.

Court of Appeals for the Eleventh Circuit.

Any changes to the orphan drug provisions could change our opportunities for, or likelihood of success in obtaining, orphan drug exclusivity and would materially adversely affect our business, results of operations, financial condition and prospects.

marketing exclusivity

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However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement.

The FDCA also provides

three years of marketing exclusivity for a NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug.

The FDCA also provides three years of marketing exclusivity for a NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug.

This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for the original non-modified version of the drug.

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Once an approval of a drug is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.

Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in mandatory revisions to the approved labeling to add new safety information;

Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with

manufacturing processes, or failure to comply with regulatory requirements, may result in mandatory revisions to the approved labeling to add new safety information;

imposition of post-market studies or clinical trials to assess new safety risks;

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The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

Other healthcare laws

Other healthcare and privacy laws

Healthcare providers, physicians, and third party payors play a primary role in the recommendation and prescription of drug products for which we obtain marketing approval.

Arrangements with third party payors, healthcare providers and

physicians, in connection with the clinical research, sales, marketing and promotion of products, once approved, and related activities, may expose a pharmaceutical manufacturer to broadly applicable fraud and abuse and other healthcare laws and regulations.

Arrangements with third party payors, healthcare providers and physicians, in connection with the clinical research, sales, marketing and promotion of products, once approved, and related activities, may expose a pharmaceutical manufacturer to broadly applicable fraud and abuse and other healthcare laws and regulations.

In the United States, these laws include, without limitation, state and federal anti-kickback, false claims, physician payment transparency, price transparency, and patient data privacy and security laws and regulations, including but not limited to those described below:

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or knowingly concealing or knowingly and improperly avoiding or decreasing such an obligation.

A person or entity does not need to have actual knowledge of these statutes or specific intent to violate them in order to have committed a violation.

or entity does not need to have actual knowledge of these statutes or specific intent to violate them in order to have committed a violation.

Violations of the False Claims Act can result in civil penalties of up to more than $25,000 per false claim or statement (an amount adjusted annually for inflation) plus three times the amount of damages sustained by the government;

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• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, which impose requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates that perform services for them that involve the creation, use, receipt, maintenance or disclosure of individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information;

Insurance Program to report annually to the CMS, under the Open Payments Program, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) , nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants, certified nurse-midwives, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;

• the federal Physician Payments Sunshine Act, created under Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively, the ACA, and its implementing regulations, which require certain manufacturers of drugs, devices, biological products and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to CMS, under the Open Payments Program, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) , nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants, certified nurse-midwives, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;

• analogous state and foreign laws and regulations, such as state and foreign anti-kickback, false claims, consumer protection, transparency and disclosure laws, and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial insurers;

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If any such actions are instituted against a pharmaceutical manufacturer, and it is not successful in defending itself or asserting its rights, those actions could have a significant impact on its business, including the imposition of significant civil, criminal and administrative penalties, damages, disgorgement, imprisonment, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, reporting obligations and oversight if a pharmaceutical manufacturer becomes subject to integrity and oversight agreements to resolve allegations of non-compliance, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of operations, any of which could adversely affect a pharmaceutical manufacturer’s ability to operate its business and the results of operations.

In addition, commercialization of any drug product outside the United States will also likely be subject to foreign equivalents of the healthcare laws mentioned above, among other foreign laws.

commercialization of any drug product outside the United States will also likely be subject to foreign equivalents of the healthcare laws mentioned above, among other foreign laws.

In the U.S., numerous federal and state laws, and regulations, including state data breach notification laws, state health information privacy laws, and federal and state consumer protection laws, govern the collection, use, disclosure, and protection of health-related and other personal information.

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GDPR (together with the EU GDPR, the GDPR) which sits alongside the U.K.

Data Protection Act 2018.

Data Protection Act 2018 (as amended by the U.K.

Data (Use and Access) Act 2025).

The GDPR is wide-ranging in scope and imposes numerous requirements on controllers (and in more limited cases, processors) that process personal data (i.e., data relating to identified or identifiable individuals), including requirements around (among others):

(i) accountability and transparency, (ii) processing personal data lawfully, including specific

requirements for obtaining valid consent where consent is the legal basis for processing, (iii) responding to individuals’ requests to exercise their rights in respect of their personal data, (iv) implementing safeguards to protect the security and confidentiality of personal data and to provide notification of personal data breaches to data protection authorities and affected individuals in certain circumstances, (v) having data processing agreements with third parties who process personal data on our behalf, and undertaking due diligence in relation to such third-party processors, and (vi) considering data protection when any new products or services are developed and designed, as well as obligations for data protection impact assessments.

(i) accountability and transparency, (ii) processing personal data lawfully, including, for example, specific requirements for obtaining valid consent where consent is the legal basis for processing, (iii) responding to individuals’ requests to exercise their rights in respect of their personal data, (iv) implementing safeguards to protect the security and confidentiality of personal data and to provide notification of personal data breaches to data protection authorities and affected individuals in certain circumstances, (v) having data processing agreements with third parties who process personal data on our behalf, and undertaking due diligence in relation to such third-party processors, and (vi) considering data protection when any new products or services are developed and designed, as well as obligations for data protection impact assessments.

The EU GDPR also prohibits the international transfer of personal data from the EEA to the United States and other countries that are not recognized as having “adequate” data protection laws by the European Commission unless the parties to the transfer have implemented specific safeguards to protect the transferred personal data or a derogation under the EU GDPR can be relied upon.

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A TIA, among other things, assesses laws governing access to personal data in the recipient country and considers whether supplementary measures that provide privacy protections additional to those provided under the EU SCCs will need to be implemented to ensure an “essentially equivalent” level of data protection to that afforded in the EEA.

A further potential safeguard is the EU-US Data Privacy Framework which facilitates transfers of personal data from the EU to entities in the US which are self-certified to the DPF.

A further potential safeguard is the EU-US Data Privacy Framework (DPF) which facilitates transfers of personal data from the EU to entities in the US which are self-certified to the DPF.

Underpinning the DPF is an “adequacy decision” from the European Commission which can be relied on also by entities making transfers under the EU SCCs to the U.S.

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GDPR) or 4% of annual global revenues, whichever is greater.

The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the EU GDPR.

The GDPR may increase our responsibility and liability in relation to personal data that we process where such processing is subject to the GDPR, and we may be required to put in place additional mechanisms to ensure compliance with the GDPR, including as implemented by individual countries in the EEA or required in connection with our clinical trials.

Compliance with the GDPR is a rigorous and time-intensive process that increases our cost of doing business and increases risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities.

Current and future healthcare reform legislation

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Among other reforms, the IRA imposes inflation rebates on drug manufacturers for products reimbursed under Medicare Parts B and D if the prices of those products increase faster than inflation;

implements changes to the Medicare Part D benefit that, beginning in 2025, will cap benefit annual out-of-pocket spending at $2,000, while imposing new discount obligations for pharmaceutical manufacturers (requiring manufacturers to pay 10% of the negotiated price of brands, biologics and biosimilar products when Medicare Part D beneficiaries are in the initial coverage phase, and 20% of the negotiated price during the catastrophic phase of Medicare Part D coverage);

and, beginning in 2026, establishes a “maximum fair price” for a fixed number of high spend pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with the Centers for Medicare and Medicaid Services.

The IRA explicitly excludes from price negotiation orphan drugs designated for only one rare disease or condition and for which the only approved indication is for such disease or condition.

However, those drugs with multiple orphan designations are not explicitly excluded from drug price negotiation.

Since its enactment, CMS has taken a number of steps to implement various drug pricing provisions of the IRA.

This includes, without limitation, issuing new and updated guidance detailing the requirements and parameters of the price negotiation process for products subject to the “maximum fair price” program under the IRA;

releasing the initial list of 10 drugs covered under Medicare Part D that were subject to the first round of price negotiations under the program and subsequently announcing the “maximum fair prices” that will apply for such products in price applicability year 2026;

and releasing a list of Medicare Part B products with an adjusted coinsurance rate based on the inflationary rebate provisions of the IRA.

implements changes to the Medicare Part D benefit that, beginning in 2025, capped benefit annual out-of-pocket spending at $2,000, while imposing new discount obligations for pharmaceutical manufacturers (requiring manufacturers to pay 10% of the negotiated price of brands, biologics and biosimilar products when Medicare Part D beneficiaries are in the initial coverage phase, and 20% of the negotiated price during the catastrophic phase of Medicare Part D coverage);

and establishes a “maximum fair price” for a fixed number of high spend pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with the CMS.

Under the current statute, for a drug product to be considered a qualifying single source drug that may be selected by CMS for price negotiation under the "maximum fair price" program, at least seven years must have elapsed since the biological product was licensed by the FDA.

However, the current administration has expressed interest in working with Congress to align the treatment of small molecule prescription drugs with that of biological products.

When originally enacted, the IRA explicitly excluded from price negotiations orphan drugs designed for only one rare disease or condition and for which the only active approved indication is for such disease or condition.

However, the One Big Beautiful Bill Act, signed into law on July 4, 2025, amended the applicable statute to broaden the orphan drug exclusion such that products with more than one orphan designation and more than one approved indication will remain exempt from price negotiations, so long as each approved indication is for a rare disease or condition.

Since its enactment, CMS has taken a number of steps to implement various drug pricing provisions of the IRA, including negotiating and publishing "maximum fair prices" for drugs selected under the IRA's price negotiation framework.

It remains to be seen how the maximum fair prices or other drug pricing provisions imposed by the IRA will affect orphan drug and small molecule development or the broader pharmaceutical industry.

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Some states have also established prescription drug affordability boards tasked with identifying certain high-cost prescription products that may pose affordability challenges for consumers and payors, conducting cost reviews on such products, and, in some circumstances, imposing upper payment limits on such products.

reduction in coverage or payment from private payors, and may otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

These laws, regulations, and actions, and any state or federal healthcare reform measures that may be adopted in the future, could reduce coverage or reimbursement from Medicare and other government programs, may result in a similar reduction in coverage or payment from private payors, and may otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

Additionally, we expect to experience pricing pressures in connection with the sale of any future approved product candidates due to the trend toward managed healthcare, the increasing influence of health maintenance organizations, cost containment initiatives and additional legislative and regulatory changes.

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Once the CTA is approved in accordance with a country’s requirements, the corresponding clinical trial may proceed.

Under the current regime (the EU Clinical Trials Regulation 536/2014, which has been in effect since January 31, 2022 replacing the EU Clinical Trials Directive 2001/20/EC) all suspected unexpected serious adverse reactions to the investigated drug that occur during the clinical trial have to be reported to the NCA and ECs of the Member State where they occurred.

investigated drug that occur during the clinical trial have to be reported to the NCA and ECs of the Member State where they occurred.

In addition to data privacy requirements, many jurisdictions have mandatory clinical trial information obligations on sponsors.

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It is possible for competitors to access and use this data in their own research and development programs anywhere in the world, once this data is in the public domain.

On May 3, 2022, the European Commission published a proposal for a regulation on the European Health Data Space, or EHDS, which aims to further enable exchange of electronic health data both for primary use (among national EU healthcare systems for patient care) and secondary use (among private companies and regulators to enable scientific research).

The regulation was adopted by the European Parliament in April 2024 and by the European Council in 2025 and will enter into force twenty days after its publication in the Official Journal of the European Union.

This will impose new obligations, but also create opportunities, for entities engaged in health-related research to share and access health data on a scale much larger than what is foreseen under current applicable transparency provisions.

The European Health Data Space Regulations (the "EHDS Regulations") came into force on March 26, 2025.

The aims of the EHDS Regulations are to provide individuals with more control over their electronic health data, enable cross-border sharing of European Health Data ("EHD") between national EU healthcare systems and facilitate the sharing of EHD for secondary research purposes.

The EHDS Regulations impose new obligations, but also create opportunities for companies engaged in health-related research to share and access health data on a large scale.

Although the EHDS Regulations have come into force, key obligations will not apply until March 2029.

European drug review and approval

To obtain a marketing authorization in the EEA (comprising the EU Member States, plus Norway, Iceland, and Liechtenstein), a company may submit marketing authorization applications either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EEA Member States (decentralized procedure, national procedure, or mutual recognition procedure).

new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, autoimmune and other immune dysfunctions, viral diseases, or diabetes.

The centralized procedure is compulsory for certain medicines, including those produced by biotechnology, products designated as orphan medicinal products, advanced therapy medicinal products (gene therapy, somatic cell therapy and tissue-engineered products) and those with a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, autoimmune and other immune dysfunctions, viral diseases, or diabetes.

The centralized procedure is optional for those medicines which contain a new active substance, or which are a significant therapeutic, scientific, or technical innovation or whose authorization would be in the interest of public health.

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On April 26, 2023, the European Commission adopted a proposal for a new Regulation set to replace Regulation (EC) No 726/2004 and a new Directive replacing Directive 2001/83 on the Community Code relating to medicinal products for human use.

On December 11, 2025, the European Council and Parliament reached a provisional agreement on the proposal.

The provisional agreement is now subject to formal approval by the European Parliament and the Council before being formally adopted and entering into force upon publication in the EU's Official Journal.

If made into law, the proposals will revise and replace the existing general pharmaceutical legislation and make it more difficult to obtain orphan designation in the EEA.

If made into law, this proposal will revise the existing general pharmaceutical legislation.

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There are no international agreements on mutual recognition of authorizations in relation to medicinal products.

However, marketing authorization dossiers can be submitted to Swissmedic with clinical data, irrespective of the location where a clinical trial was conducted, that were collected in accordance with globally applicable international standards such as the Good Clinical Practice, or GCP, of the International Conference on Harmonization, or ICH, which are based on the Declaration of Helsinki.

Furthermore, if a medicinal product or procedure is already authorized in a country having equivalent medicinal product control, the results of tests carried out for this purpose shall be taken into account.

However, marketing authorization dossiers can be submitted to Swissmedic with clinical data, irrespective of the location where a clinical trial was conducted, that were collected in accordance with globally applicable international standards such as the Good Clinical Practice (GCP) guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) which are based on the Declaration of Helsinki.

Furthermore, where a medicinal product or procedure is already authorized in a country having equivalent medicinal product control, the results of tests carried out for this purpose shall be taken into account.

According to Swissmedic's practice, this includes the authorization procedures of the following countries:

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market faster.

applications, recognize the approval of medicines by Australia, Canada, Switzerland, Singapore, Japan, United States and the EU following its own abbreviated assessment.

On January 1, 2024, the MHRA launched a new International Recognition Procedure for Great Britain (England, Scotland and Wales) marketing authorization applications whereby the MHRA will, when considering such applications, recognize the approval of medicines by Australia, Canada, Switzerland, Singapore, Japan, United States and the EU following its own abbreviated assessment.

European orphan drug designation and exclusivity

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In the EEA, a “similar medicinal product” is a medicinal product containing a similar active substance or substances as contained in a currently authorized orphan medicinal product, and which is intended for the same therapeutic indication.

The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify the maintenance of market exclusivity.

The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that

the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify the maintenance of market exclusivity.

The general pharmaceutical legislative framework, as well as the framework applicable to orphan and pediatric medicinal products in the EU, is under review.

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However, some changes to the U.K.

legislation have been necessary, including the implementation of the Northern Ireland Protocol (NIP), pursuant to which the EU pharmaceutical legal framework continues to apply in Northern Ireland (subject to periodic consent of the Northern Ireland Legislative Assembly), and only products compliant with EU law can be placed in the Northern Ireland market.

This dynamic adds an extra layer of regulatory complexity for companies withing to commercialize medicinal products in Great Britain (namely, England, Wales and Scotland, as EU law continues to apply in Northern Ireland), as such companies now need to comply with separate U.K.

legislation have been necessary, including the implementation of the Northern Ireland Protocol (NIP), pursuant to which the EU pharmaceutical legal framework continued to apply in Northern Ireland (subject to periodic consent of the Northern Ireland Legislative Assembly), and only products compliant with EU law could be placed in the Northern Ireland market.

This dynamic added an extra layer of regulatory complexity for companies wanting to commercialize medicinal products in Great Britain (namely, England, Wales and Scotland, as EU law continues to apply in Northern Ireland), as such companies now need to comply with separate U.K.

regulatory legal framework.

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According to the Windsor Framework, medicinal products intended for the U.K.

market, including Northern Ireland, will be authorized by the MHRA and will bear a “U.K.

market, including Northern Ireland, are now authorized by the MHRA and must bear a “U.K.

These new measures became effective January 1, 2025.

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healthcare industry and elsewhere is cost containment.

Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular drug products.

Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular drug

In many countries, the prices of drug products are subject to varying price control mechanisms as part of national health systems.

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Any negotiated prices for any of our products covered by a Part D prescription drug plan will likely be lower than the prices we might otherwise obtain.

Additionally, beginning in 2025, manufacturers must pay additional discounts for products covered under Medicare Part D.

Additionally, since 2025, manufacturers have been obligated to pay additional discounts for products covered under Medicare Part D as a result of the IRA.

Moreover, while the MMA Part D plan policies applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policies and payment limitations in setting their own payment rates and coverage guidelines.

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The required 340B discount on a given product is calculated based on the average manufacturer price, or AMP, and Medicaid rebate amounts reported by the manufacturer.

As of 2010, the ACA expanded the types of entities eligible to receive discounted 340B pricing, although

under the current state of the law these newly eligible entities (with the exception of children’s hospitals) will not be eligible to receive discounted 340B pricing on orphan drugs.

As of 2010, the ACA expanded the types of entities eligible to receive discounted 340B pricing, although under the current state of the law these newly eligible entities (with the exception of children’s hospitals) will not be eligible to receive discounted 340B pricing on orphan drugs.

As 340B drug pricing is determined based on AMP and Medicaid rebate data, any revisions to the Medicaid rebate formula or AMP definition could cause the required 340B discount to increase.

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Efforts to control prices and utilization of pharmaceutical products and medical devices will likely continue as countries attempt to manage healthcare expenditures.

Moreover, in May 2025, the Trump Administration issued an executive order titled "Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients" Executive Order, which may have unpredictable consequences on the pricing of medicinal products in European countries.

The Executive Order required federal agencies to seek parity between U.S.

drug prices and the lowest prices in peer nations and empowers the Secretary of HHS to establish and communicate most-favored-nation price targets to manufacturers, including through rulemaking if voluntary efforts by manufacturers prove inadequate.

In accordance with this Executive Order, CMS has taken action to implement "most-favored-nation" pricing, including by announcing a new voluntary payment model where drug manufacturers may offer supplemental rebates to participating state Medicaid programs to provide such Medicaid programs with a "most favored nation" price for participating manufacturers' products, as well proposing mandatory payment models where, if finalized, manufacturers of certain Medicare Part B and Medicare Part D drugs would be assessed rebates if the prices for such product exceed those paid in economically comparable countries.

It remains to be seen how these drug pricing initiatives will affect the broader pharmaceutical industry.

Additionally, the Executive Order instructs the Department of Commerce and the U.S.

Trade Representative to take action against foreign countries that engage in practices suppressing drug prices below fair market value, which could lead to additional pricing pressure or prompt regulatory changes in foreign markets.

These measures may have unpredictable consequences on pricing of medicinal products in European countries.

Human Capital Resources

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We provide our employees with competitive salaries and bonuses, opportunities for equity ownership, development opportunities that enable continued learning and growth and a robust recognition program that recognizes and celebrates their accomplishments.

In addition, we regularly conduct an employee survey to gauge employee engagement and identify areas of focus.

Corporate and Available Information

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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