What changed in this filing

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Item 1. Business

2025-03-03 compared with 2024-02-27 · 128 added, 163 removed, 468 unchanged (38% of the section changed)

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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 (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvß6 and αvß1 integrins that we are developing for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC.

We are currently conducting a Phase 2b trial in IPF and a Phase 2a trial in PSC.

We announced positive data from our Phase 2a INTEGRIS-IPF trial in May 2023.

We are currently conducting BEACON-IPF, a 52-week, randomized, double-blind, placebo-controlled Phase 2b trial, in patients with IPF.

We announced positive interim data from our Phase 2a INTEGRIS-PSC trial in September 2023 and February 2024.

We expect to release final data from the INTEGRIS-PSC trial in mid-2024.

In January 2023, we received FDA clearance of investigational new drug application, or IND, for our third clinical program to date, PLN-101095, a dual inhibitor of integrins αvß8 and αvß1 for the treatment of solid tumors that are resistant to immune checkpoint inhibitors.

We are currently dosing the third of five planned 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.

We expect to release preliminary data from the trial in late 2024.

Our fourth program to date, PLN-101325, in development for treatment of muscular dystrophies, including Duchenne muscular dystrophy.

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.

We expect to file with regulators for first-in-human studies in the first quarter of 2024.

We have developed PLN-1474, an oral, small molecule selective inhibitor of αvß1 for the treatment of liver fibrosis associated with nonalcoholic steatohepatitis, or NASH.

PLN-1474 is Phase 2-ready, having shown an excellent safety and pharmacokinetic profile in Phase 1 trials.

PLN-1474 was licensed to Novartis in 2019.

As part of a broad strategic realignment, Novartis has discontinued clinical development in NASH and, as a result, discontinued development of PLN-1474.

In February 2023, Novartis returned global rights to PLN-1474 to Pliant.

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 that we are advancing in IPF and PSC.

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

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 United States Food and Drug Administration, or FDA and the European Medicines Agency, or EMA, for both IPF and PSC.

In addition, bexotegrast has been granted Fast Track designation by the FDA for IPF and PSC.

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

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Both have shown modest slowing of disease progression.

However, both therapies have raised significant safety and tolerability concerns.

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.

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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.

Change in FVC from Baseline of Bexotegrast 320 mg Over 12 Weeks in INTEGRIS-IPF;

Mixed Model Repeat Measures Analysis – Modified Intent to Treat Population

Proportion of Participants with FVCpp Decline ≥10% - Intent to Treat Population

Circulating PRO-C3 and Integrin beta-6 Biomarker Levels–

Change from Baseline at 4- and 12-Weeks vs Placebo

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

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.

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

Change in FVC from Baseline of Bexotegrast 320 mg Over 24 Weeks

Proportion of Patients with FVC Change from Baseline of Bexotegrast 320 mg

Over 12 and 24 Weeks versus Placebo - Intent to Treat Population

QLF Mean Percent Change from Baseline at Weeks 12 and 24 versus Placebo – Per CT Protocol Population

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.

BEACON-IPF is a multinational trial enrolling approximately 270 patients with IPF.

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.

The mean exposure duration in BEACON-IPF was approximately 17 weeks.

Overall, the percentage of IPF-related adverse events in both dose groups was comparable (approximately 10%).

The imbalance between active and placebo appears to have been driven by a low number (below 3%) of IPF-related adverse events in the placebo group.

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

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

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.

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 are currently conducting INTEGRIS-PSC, a Phase 2a trial of bexotegrast in PSC.

The trial is a 12-week multinational, randomized, double-blind, placebo-controlled trial enrolling approximately 112 PSC patients across bexotegrast doses of 40 mg, 80 mg, 160 mg and 320 mg versus placebo that will evaluate safety, tolerability and PK.

We also plan to evaluate exploratory efficacy endpoints including fibrosis biomarkers such as Pro-C3 and enhanced liver fibrosis (ELF) score, as well as alkaline phosphatase ( ALP) and liver imaging.

While the lower doses end the treatment period at 12 weeks, the 320 mg dose cohort will be allowed to continue treatment to at least 24 weeks.

In January 2024, we released 12-week data from all four dose cohorts of the INTEGRIS-PSC data.

The trial met its primary and secondary endpoints demonstrating that bexotegrast was well tolerated over a 12-week treatment period with no drug-related severe or serious adverse events (SAEs).

Notably, PSC related AEs of cholangitis and pruritis occurred at lower rates in the treated groups compared to placebo.

Bexotegrast displayed a favorable pharmacokinetic profile with exposures increasing with dose.

All bexotegrast doses reduced the fibrotic biomarkers ELF (Enhanced Liver Fibrosis score) and PRO-C3 relative to placebo at week 12 with PRO-C3 achieving statistical significance at the 40 mg and 160 mg doses.

All doses also showed improvement in liver function and bile flow as measured by MRI imaging at week 12.

In patients with elevated baseline alkaline phosphatase (ALP) levels, all bexotegrast doses showed improvement of ALP relative to placebo at week 12.

Lastly, all bexotegrast doses displayed improvement in itch relative to placebo as measured by the itch numerical rating scale, with statistical significance achieved at the 160 mg and 320 mg doses.

Change in ELF Score at 12 Weeks in INTEGRIS-PSC - Single Doses, Pooled Doses and Pooled Placebo

We are planning to share data from the INTEGRIS-PSC trial with regulatory authorities to discuss the path to registration.

Twenty-four week data from the 320 mg dose group of the INTEGRIS-PSC trial is expected in mid-2024.

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.

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

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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 third 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.

We expect to release preliminary data from the trial in late 2024.

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

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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.

We expect to file with regulators for first-in-human studies in the first quarter of 2024 .

PLN-1474 for Treatment of Liver Fibrosis Associated with NASH

We have developed a clinical stage product candidate, PLN-1474, which is an oral, small molecule, selective inhibitor of TGF-β activation by the integrin αvß1 in development for treatment of advanced liver fibrosis associated with NASH.

αvß1 serves as an activator of TGF-β and its expression has been shown to be upregulated in hepatic stellate cells in late-stage NASH-associated liver fibrosis.

PLN-1474 has completed a first-in-human, randomized, double-blind, placebo-controlled Phase 1 dose escalation trial that enrolled 84 healthy volunteers across single ascending dose and multiple ascending dose groups.

Results showed that PLN-1474 was rapidly absorbed and well tolerated with no dose- or treatment-limiting toxicities observed with adverse events that were mostly mild with no severe or serious adverse events observed.

In October 2019, we entered into a collaboration and license agreement with Novartis in which Novartis licensed global rights to PLN-1474.

Pursuant to the terms of the agreement, we received an upfront $50.0 million license fee and a $25.0 million contingent payment upon first-patient first-dose in the Phase 1 clinical trial of PLN-1474.

As part of a broad strategic realignment, Novartis has discontinued clinical development in NASH and, as a result, discontinued development of PLN-1474.

In February 2023, Novartis returned global rights to PLN-1474 to Pliant.

Please refer to Note 8 to our financial statements appearing elsewhere in this Annual Report for further information about the license and collaboration.

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.

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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 NASH program at Allergan.

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

Prior to Allergan, Dr.

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

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

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

Both IPF and PSC are orphan indications that we believe we can commercialize on our own in key geographies using targeted sales forces.

• 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.

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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 NASH.

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.

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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., Morphic Therapeutics, Inc., Novartis AG, Scholar Rock, Inc.

and Takeda Pharmaceutical Company.

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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, BridgeBio Pharma Inc, Syndax Pharmaceuticals Inc., Endeavor BioMedicines, Inc., and Avalyn Pharma Inc..

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, NGM Biopharmaceuticals, Inc.

and Escient Pharmaceuticals, Inc.

There are currently no FDA-approved therapies for the treatment of NASH.

There are a number of companies developing product candidates for the treatment of NASH including 89bio, Inc., AbbVie Inc., Akero Therapeutics, Inc., Amgen Inc., AstraZeneca plc, Boehringer Ingelheim, Bristol Myers Squibb Co., Cascade Pharmaceuticals, Inc., Cirius Therapeutics, Inc., Dr.

Falk Pharma GmbH, Eli Lilly & Company, Enanta Pharmaceuticals, Inc., Gannex Pharma Co., Ltd., Galectin Therapeutics Inc., Gilead Sciences, Inc., Genfit SA, GlaxoSmithKline plc, Inventiva Pharma, Ionis Pharmaceuticals, Inc., Johnson & Johnson, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., NGM Biopharmaceuticals, Inc., NorthSea Therapeutics B.V., Novo Nordisk, Pfizer Inc.,Roche Holding AG, Regeneron Pharmaceuticals, Inc., Sanofi S.A., Takeda Pharmaceutical Company, Terns Pharmaceuticals, Inc., Viking Therapeutics, Inc.

and Zydus Therapeutics Inc.

Most of the drugs currently in development for NASH are focused on decreasing liver fat or improving liver inflammation as opposed to direct liver anti-fibrotic approaches.

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.

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.

Intellectual Property

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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 13, 2024, twelve U.S.

patents and seventeen foreign patents have been issued, granted or allowed.

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.

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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 have 36 pending patent applications to that technology in the United States and foreign jurisdictions, and one issued foreign patent.

Patents that may issue from these company owned applications are generally expected to expire between the years 2040 to 2044, subject to possible patent term adjustment and/or extension.

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.

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

These antibody patents and patents that may issue from company owned antibody applications are generally expected to expire between the years 2040 to 2045, subject to possible patent term adjustment and/or extension.

Trademark Protection

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We believe that our focus and expertise will help us develop products based on our proprietary intellectual property.

License Agreements

Novartis Collaboration and License Agreement

In October 2019, we entered into a collaboration and license agreement, or the Novartis Agreement, with Novartis Institutes for Biomedical Research, Inc., or Novartis, for the research, development, and commercialization of PLN-1474.

Pursuant to the terms of the Novartis Agreement, t he PLN-1474 IND was transferred to Novartis in the first quarter of 2021 following completion of our first-in-human Phase 1 clinical trial.

Upon transfer of the IND, Novartis assumed responsibility for all future development, manufacturing, and commercialization and we earned research and development services revenues in performing certain activities outlined in the Novartis Agreement.

All such services were substantially complete as of December 31, 2022.

In addition, the Novartis Agreement provided for an early research program for up to three additional integrin targets, or the Research Targets.

The research term, as amended in 2022, concludes in the first quarter of 2023.

During the research term, we collaborate with Novartis to biologically validate certain potential Research Targets and identify and synthesize potential research compounds for each Research Target in accordance with the applicable research plan.

In the second quarter of 2022 we validated one of the Research Targets and began synthesizing potential research compounds.

As part of a broad strategic realignment, Novartis has discontinued clinical development in NASH and, as a result, discontinued development of PLN-1474.

In February 2023, Novartis issued a termination notice for the collaboration and license agreement, and returned global rights to Pliant for PLN-1474 as well as the early research targets and associated compounds.

Please refer to Note 8 to our financial statements appearing elsewhere in this Annual Report for further information about the license and collaboration.

Manufacturing

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Government Regulation

The FDA, CMS,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, and distribution of drugs, such as those we are developing.

The FDA, Centers for Medicare and Medicaid Services, or CMS,U.S.

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.

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Failure to comply with the applicable U.S.

requirements at any

time during the product development process, approval process or after approval, may subject an applicant to a variety of administrative or judicial sanctions, such as the FDA’s refusal to approve pending New Drug Applications, or NDAs, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.

requirements at any time during the product development process, approval process or after approval, may subject an applicant to a variety of administrative or judicial sanctions, such as the FDA’s refusal to approve pending New Drug Applications, or NDAs, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.

The process required by the FDA before a drug may be marketed in the United States generally involves the following:

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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.

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.

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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Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required

specifications.

Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP requirements.

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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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Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same active ingredient for the same indication is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market demand.

Further, the FDA may approve more than one

product for the same orphan indication or disease as long as the products contain different active ingredients.

Further, the FDA may approve more than one product for the same orphan indication or disease as long as the products contain different active ingredients.

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.

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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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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

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

or imposition of distribution or other restrictions under a REMS program.

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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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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.

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;

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;

• the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters;

• 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;

• 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 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 the Centers for Medicare and Medicaid Services, or 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;

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;

• 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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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.

For example, in June 2018, the State of California enacted the California Consumer Privacy Act of 2018, or the CCPA, which came into effect on January 1, 2020 and provides new data privacy rights for consumers and new operational requirements for companies, which may increase our compliance costs and potential liability.

For example, in June 2018, the State of California enacted the California Consumer Privacy Act of 2018, or the CCPA, which came into effect on January 1, 2020 and provides data privacy rights for consumers and operational requirements for companies, which may increase our compliance costs and potential liability.

The CCPA gives California residents expanded rights to access and delete their personal information, opt out of certain personal information sharing, and receive detailed information about how their personal information is used.

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While there is currently an exception for protected health information that is subject to HIPAA and clinical trial regulations, as currently written, the CCPA impacts certain of our business activities.

The CCPA could mark the beginning of a trend toward more stringent state privacy legislation in the U.S., which could increase our potential liability and adversely affect our business.

Many states have followed California in implementing comprehensive state privacy laws, and the various compliance requirements affiliated with these laws could increase our potential liability and adversely affect our business.

In the event we decide to conduct clinical trials or continue to enroll subjects in our ongoing or future clinical trials, we may be subject to additional privacy restrictions.

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has implemented the EU GDPR as the U.K.

GDPR which sits alongside the U.K.

Data Protection Act 2018, or the U.K.

GDPR, and together with the EU GDPR, the GDPR.

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

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

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

Data Protection Act 2018.

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.

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.

One of the primary safeguards allowing U.S.

companies to import personal data from the EEA had historically been certification to the EU-U.S.

Privacy Shield framework administered by the U.S.

Department of Commerce.

However, the European Court of Justice, or the CJEU, issued a decision in July 2020 which invalidated the EU-U.S.

Privacy Shield framework for purposes of international transfers (Schrems II) and imposed further restrictions on using the specific safeguard standard contractual clauses (EU SCCs) including, a requirement for companies to carry out a transfer privacy impact assessment, or a TIA.

companies to import personal data from the EEA are standard contractual clauses (EU SCCs) including, a requirement for companies to carry out a transfer privacy impact assessment, or a TIA.

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.

Following that decision, the Swiss Federal Data Protection and Information Commissioner took a similar view and considered that data transfers based on the Swiss-U.S.

Privacy Shield framework are no longer lawful (despite the fact that Schrems II is not directly applicable in Switzerland (unless the Swiss based company is subject to the EU GDPR) although the Swiss-U.S.

Privacy Shield has not been officially invalidated).

On October 7, 2022, U.S.

President Biden introduced an Executive Order to facilitate a new Trans-Atlantic Data Privacy Framework, or the DPF, and on July10, 2023, the European Commission adopted its Final Implementing Decision granting the U.S.

adequacy, or the Adequacy Decision, for EU-U.S.

transfers of personal data for entities self-certified to the DPF.

Entities relying on EU SCCs for transfers to the U.S.

are also able to rely on the analysis in the Adequacy Decision as support for their TIA regarding the equivalence of U.S.

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.

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.

as support for their TIA regarding the equivalence of U.S.

national security safeguards and redress.

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Government has published its own form of EU SCCs, known as the International Data Transfer Agreement and an International Data Transfer Addendum to the new EU SCCs.

Information Commissioner’s Office, or the ICO, has also published its own version of the TIA and revised guidance on international transfers, although companies may choose to either use the EU-style or U.K.-style TIA.

Information Commissioner’s Office, or the ICO, has also published its own version of the TIA although companies may choose to either use the EU-style or U.K.-style TIA.

Further, on September 21, 2023, the U.K.

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regulations to implement the U.K.-U.S.

Personal data may now be transferred

from the U.K.

Personal data may now be transferred from the U.K.

under the U.K.-U.S.

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For example, in the United States, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, collectively known as the ACA, was enacted, which substantially changed the way healthcare is financed by both governmental and private payors, and significantly affected the pharmaceutical industry.

The ACA, among other things, addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, 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, established annual fees and taxes on manufacturers of certain branded prescription drugs, and created a new Medicare Part D coverage gap discount program (which has been subsequently eliminated by the Inflation Reduction Act of 2022, or the IRA), in which manufacturers were required to provide certain point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D.

There have been numerous historic judicial, administrative, executive, and legislative challenges and amendments (including recent amendments that aimed at expanding access to care and reforming prescription drug pricing) to certain aspects of the ACA and other healthcare laws.

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

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

This includes, without limitation, issuing new guidance on June 30, 2023 detailing the requirements and parameters of the first round of price negotiations, to take place during 2023 and 2024, for products subject to the “maximum fair price” provision that would become effective in 2026 and, on August 29, 2023, releasing the initial list of 10 drugs subject to price negotiations.

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.

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.

Several pharmaceutical manufacturers and other industry stakeholders have challenged the law, including through lawsuits brought against the HHS, the Secretary of HHS, CMS, and the CMS Administrator challenging the constitutionality and

administrative implementation of the IRA’s drug price negotiation provisions.

We cannot predict whether the IRA, or any of its component parts, will be overturned, repealed, replaced, or amended nor can we predict the likelihood, nature, or extent of other health reform initiatives that may arise from future legislation, administrative, or other action.

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Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs.

On June 28, 2024, the U.S.

Supreme Court issued an opinion holding that courts reviewing agency action pursuant to the Administrative Procedure Act, or the APA, “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision will have a significant impact on how lower courts evaluate challenges to agency interpretations of law, including those by the FDA, CMS and other agencies with significant oversight of the biopharmaceutical industry.

The new framework is likely to increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases.

As a result, significant regulatory policies may be subject to increased litigation and judicial scrutiny.

Any resulting changes in regulation may result in unexpected delays, increased costs, or other negative impacts on our business that are difficult to predict.

At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control biopharmaceutical and biologic product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, marketing cost disclosure and other transparency measures, and, in some cases, legislation, regulation or other guidance designed to encourage or facilitate importation from other countries and bulk purchasing.

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 payers, conducting cost reviews on such products, and, in some circumstances, imposing upper payment limits on such products.

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 payers, 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.

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.

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

available certain information stemming from clinical studies, either proactively or in response to third party requests.

In the EU this is under the Transparency Regulation No 1049/ 2001, EMA Policy 0043, EMA Policy 0070, as well as the Clinical Trials Regulation No 536/2014, all of which impose on sponsors the obligation to make publicly available certain information stemming from clinical studies, either proactively or in response to third party requests.

In the EU, the transparency framework provides for a wide right for (EU-based at the moment) interested parties to submit an access to documents request to the EMA for information included in the marketing authorization application dossier for approved medicinal products.

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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).

Whilst the regulation is currently under discussions among the EU legislators, the text is expected to be finalized by the end of 2023 and for the EHDS to become reality in 2025.

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.

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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).

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.

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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Australia, the member states of the EU, the EFTA states in the EEA (Liechtenstein, Norway and Iceland), Japan, Canada, New Zealand, Singapore, the United Kingdom and the United States.

Now that the U.K.

(which comprises Great Britain and Northern Ireland) has left the EU, Great Britain will no longer be covered by centralized marketing authorizations (under the Northern Irish Protocol, centralized marketing authorizations will continue to be recognized in Northern Ireland).

Since the U.K.

(which comprises Great Britain and Northern Ireland) left the EU, Great Britain is no longer covered by centralized marketing authorizations, but they continued to be recognized in Northern Ireland under the Northern Irish Protocol.

However, this has changed since January 1, 2025, when new measures implemented by the Windsor Framework came into effect in the U.K.

The new measures include, among others, the removal of EU licensing processes in relation to Northern Ireland for novel medicines (i.e.

those that were authorized under the EU centralized procedure).

This means that marketing authorizations granted by the European Commission are no longer valid in Northern Ireland.

Companies therefore no longer need to apply for separate licenses for Great Britain and Northern Ireland to market the same novel medicines across the whole U.K.

All medicinal products with an existing centralized marketing authorization were automatically converted to Great Britain marketing authorizations on January 1, 2021.

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market faster.

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.

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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However, as U.K.

legislation now has the potential to

diverge from EU legislation, the future regulatory regime which applies to products and the approval of product candidates in the U.K.

legislation now has the potential to diverge from EU legislation, the future regulatory regime which applies to products and the approval of product candidates in the U.K.

It remains to be seen how Brexit will impact regulatory requirements for product candidates and products in the U.K.

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The MHRA published detailed guidance for industry and organizations to follow which will be updated as the U.K.’s regulatory position on medicinal products evolves over time.

‘Retained EU law,’ which has prevented substantial divergence to the regulation of medicines.

‘Retained EU Law,’ generally has prevented substantial divergence to the regulation of medicines.

However, some changes to the U.K.

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regulatory legal framework.

Government and the European Union recently adopted a new agreement, the “Windsor Framework,” which will replace the Northern Ireland Protocol.

In 2023, the U.K.

enacted the Retained EU Law (Revocation and Reform) Act 2023 which allows for the revocation of Retained EU Law.

In particular, this Act:

• revokes a long list of specific EU-derived subordinate legislation and retained direct EU legislation,

• renames any continuing Retained EU Law as ‘assimilated law’,

• changes the way in which assimilated law is interpreted by removing the general principles of EU law as an aid to interpretation and ceasing the application of the supremacy of EU law from 1 January 2024, and

• provides ministers with wide-ranging powers to restate, revoke or replace assimilated law.

Government and the European Union recently adopted a new agreement, the “Windsor Framework,” which modifies the Northern Ireland Protocol.

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.

These new measures will be implemented from January 1, 2025.

These new measures became effective January 1, 2025.

The Trade and Cooperation Agreement signed between the U.K.

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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.

Any reduction in payment restrictions in Part D

coverage that results from the MMA may result in a similar reduction in payment restrictions from non-governmental payors.

Any reduction in payment restrictions in Part D coverage that results from the MMA may result in a similar reduction in payment restrictions from non-governmental payors.

For a drug product to receive federal reimbursement under the Medicaid or Medicare Part B programs or to be sold directly to U.S.

government agencies, the manufacturer must extend discounts to entities eligible to participate in the 340B drug pricing program.

government agencies, the manufacturer must participate in certain other Federal health care programs and also extend discounts to entities eligible to participate in the 340B drug pricing program.

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

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.

The 340B drug pricing program may be subject to future changes in light of ongoing litigation and attempts to reform the program, including legislative proposals to reform the 340B program.

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In December 2021, the EU adopted a new Regulation on Health Technology Assessment.

The Regulation creates collaborative structures and procedures that allow Member States to carry out joint clinical assessments, effect joint clinical consultations and identify jointly emerging health technologies and will come into effect in 2025.

Other countries may allow companies to fix their own prices for products but monitor and control product volumes and issue guidance to physicians to limit prescriptions.

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We believe that each employee brings unique perspectives and strengths, and by embracing these strengths, we can do our best work for patients.

We focus on recruiting, retaining, and developing employees from a diverse range of backgrounds to conduct our research, development, and clinical activities.

We focus on recruiting, retaining, and developing employees from a wide range of backgrounds to conduct our research, development, and clinical activities.

As part of our measures to attract and retain a highly skilled workforce, we offer a competitive suite of benefits to our full-time employees to help support their health and financial well-being, including medical, dental and vision insurance, life insurance, 401k retirement program with a company match, flexible spending accounts, paid holiday and vacation time, and flexible work arrangements.

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We were incorporated under the laws of the State of Delaware in June 2015.

Our principal executive office is located at 260 Littlefield Avenue, South San Francisco, California 94080, and our telephone number is (650) 481-6770.

Our principal executive office is located at 331 Oyster Point Boulevard, South San Francisco, California 94080, and our telephone number is (650) 481-6770.

Our website address is https://pliantrx.com.

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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