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Item 1. Business

2026-02-26 compared with 2025-02-27 · 159 added, 128 removed, 1002 unchanged (22% of the section changed)

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We are a biopharmaceutical company that develops and commercializes innovative products to enhance cancer care and improve treatment outcomes for patients.

We are currently commercializing NERLYNX, an oral version of neratinib, for the treatment of HER2-positive breast cancer.

We are currently commercializing NERLYNX, an oral version of neratinib, for the treatment of certain HER2-positive breast cancers.

Additionally, we have in-licensed, and are responsible for global development and commercialization of, alisertib.

Alisertib is a selective, small-molecule inhibitor of Aurora Kinase A that is designed to disrupt mitosis leading to apoptosis of rapidly proliferating tumor cells that are dependent on Aurora Kinase A.

Prior to our licensing alisertib from Takeda, alisertib was tested in over 1,300 patients who were treated across 22 company-sponsored trials resulting in a large, well-characterized clinical safety database.

Based on information in this database, we believe alisertib has potential application in the treatment of range of different cancer types, including hormone receptor positive breast cancer, triple negative breast cancer, small cell lung cancer and head and neck cancer.

Prior to our licensing alisertib from a subsidiary of Takeda Pharmaceutical Company Limited (“Takeda”), alisertib was tested in over 1,300 patients who were treated across 22 company-sponsored trials resulting in a large, well-characterized clinical safety database.

Based on information in this database, we believe alisertib has potential application in the treatment of a range of different cancer types, including hormone receptor-positive breast cancer, triple negative breast cancer and small cell lung cancer.

We intend to pursue development of alisertib initially in small cell lung cancer and hormone receptor-positive breast cancer.

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Non-small cell lung cancer

Breast cancer is the leading cause of cancer death among women worldwide, with approximately one million new cases reported each year and more than 400,000 deaths per year.

Breast cancer is the leading cause of cancer death among women worldwide, with approximately 2.3 million new cases reported each year and more than 670,000 deaths globally per year.

Up to 20% of breast cancer tumors show over-expression of the HER2 protein.

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As of December 31, 2025, NERLYNX has received approval for the treatment of certain patients with extended adjuvant and/or metastatic HER2-positive breast cancer in more than 40 countries outside the United States, including the European Union (“EU”), China, Latin America, Australia, Canada, and Hong Kong.

We are currently a party to several sub-licenses in various regions outside the United States, including Europe (excluding Russia and Ukraine), Australia, Canada, China, Southeast Asia, Israel, South Korea, and various countries and territories in Central America, South America, Africa and the Middle East.

In September 2022, we entered into an exclusive license agreement with a subsidiary of Takeda Pharmaceutical Company Limited (“Takeda”) to license the worldwide research and development and commercial rights to alisertib.

We are currently party to several sub-licenses in various regions outside the United States, including Europe (excluding Ukraine), Australia, Canada, China, Southeast Asia, Israel, South Korea, Russia and various countries and territories in Central America, South America, Africa and the Middle East.

In September 2022, we entered into an exclusive license agreement with Takeda to license the worldwide research and development and commercial rights to alisertib.

Alisertib is an investigational, reversible, ATP-competitive inhibitor that is designed to be highly selective for Aurora Kinase A.

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HER2-Positive Breast Cancer Overview

Breast cancer is the leading cause of cancer death among women worldwide, with approximately 1 million new cases reported each year and more than 400,000 deaths per year.

Up to 20% of breast cancer tumors show over-expression of the HER2 protein.

Women with breast cancer that over-expresses HER2 are at greater risk for disease recurrence, progression and death than women whose tumors do not over-express HER2.

Breast cancer is the leading cause of cancer death among women worldwide.

In 2022, an estimated 2.3 million new cases and 670,000 breast cancer-related deaths occurred.

Up to 20% of breast cancer tumors show over-expression of the HER2 protein and HER2 status is an important prognostic and predictive factor of breast cancer.

Therapeutic strategies have been developed to block HER2 in order to improve the treatment of this type of breast cancer.

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In addition, we are aware of numerous additional ongoing clinical trials involving other drug candidates used alone or in combination with existing drugs to treat patients with breast cancer.

In addition, we are also aware of a Phase III trial in patients with high risk HER2-positive early stage breast cancer with residual disease after neoadjuvant treatment that is testing the combination of KADCYLA plus tucatinib versus KADCYLA alone (the CompassHER2 RD Trial), as well as a Phase III trial in patients with high risk HER2-positive early stage breast cancer with residual disease after neoadjuvant treatment that is testing fam-trastuzumab deruxtecan versus KADCYLA alone (the DESTINY-Breast05 Trial).

We believe that there are approximately 30,000 patients in the United States and 37,000 patients in the EU with early stage HER2-positive breast cancer that get treated with adjuvant treatment.

We also believe that there are approximately 6,400 patients in the United States with third-line and 4,700 patients in the United States with fourth-line HER2-positive metastatic breast cancer.

In addition, we are also aware of a Phase III trial in patients with high risk HER2-positive early stage breast cancer with residual disease after neoadjuvant treatment that is testing the combination of KADCYLA plus tucatinib versus KADCYLA alone (the “CompassHER2 RD Trial”), and the data from the completed Phase III trial in patients with high risk HER2-positive early stage breast cancer with residual disease after neoadjuvant treatment that evaluated fam-trastuzumab deruxtecan versus KADCYLA alone (the “DESTINY-Breast05 Trial”).

We believe that there are approximately 30,000 patients in the United States and 37,000 patients in the EU with early stage HER2-positive breast cancer who are treated with adjuvant therapy.

We also believe that there are approximately 6,400 patients in the United States with third-line HER2-positive metastatic breast cancer.

The number of patients with third-line or later HER2-positive metastatic breast cancer may decrease in future years as the introduction of new neoadjuvant, adjuvant and extended adjuvant treatments may reduce the number of patients with recurrence of HER2-positive breast cancer and therefore reduce the number of patients with HER2-positive metastatic breast cancer.

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For the pre-defined subgroup of patients with hormone receptor-negative disease, the results of the trial demonstrated that treatment with neratinib resulted in a hazard ratio of 0.95 (p = 0.762).

The results of the ExteNET trial showed that after two years of follow-up, for patients with hormone receptor positive, HER2-positive early stage breast cancer patients who were treated within one year after the completion of trastuzumab based adjuvant therapy, iDFS was 95.3% in the patients treated with neratinib compared with 90.8% in those receiving placebo (hazard ratio = 0.49;

The results of the ExteNET trial showed that after two years of follow-up, for patients with hormone receptor-positive, HER2-positive early stage breast cancer who were treated within one year after the completion of trastuzumab based adjuvant therapy, iDFS was 95.3% in the patients treated with neratinib compared with 90.8% in those receiving placebo (hazard ratio = 0.49;

(0.30, 0.78);

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Patients who received neratinib in this trial did not receive any prophylaxis with antidiarrheal agents to prevent the neratinib-related diarrhea.

In October 2020, we announced that efficacy results of neratinib in HER2-positive, hormone receptor positive, or HR+, early stage breast cancer, (“eBC”) from the Phase III ExteNET trial were published in Clinical Breast Cancer .

The manuscript presented data focusing on HR+ patients who initiated treatment within a year of completing an adjuvant trastuzumab containing treatment (HR+ /< 1 yr) and subgroups of clinical interest including patients who did not achieve a pathological complete response (no pCR) after neoadjuvant treatment and therefore were at a high risk of disease recurrence (HR+/ <1 yr, no pCR).

In October 2020, we announced that efficacy results of neratinib in HER2-positive, hormone receptor-positive (“HR+”), early stage breast cancer from the Phase III ExteNET trial were published in Clinical Breast Cancer .

The manuscript presented data focusing on hormone receptor-positive patients who initiated treatment within a year of completing an adjuvant trastuzumab containing treatment (HR+ /< 1 yr) and subgroups of clinical interest including patients who did not achieve a pathological complete response (no pCR) after neoadjuvant treatment and therefore were at a high risk of disease recurrence (HR+/ <1 yr, no pCR).

In the HR+ /< 1 yr patient population, the absolute 5-year invasive disease-free survival benefit versus placebo was 5.1% (HR=0.58, 95% CI 0.41–0.82) and absolute 8-year overall survival benefit was 2.1%.

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The median cumulative duration of grade 3 diarrhea ranged from 2 – 2.5 days across the CONTROL DE study cohorts for the entire 12-month treatment period (compared with 5.0 days for ExteNET).

The proportion of patients discontinuing neratinib because of diarrhea was decreased in both DE cohorts (DE1 3%;

The proportion of patients discontinuing neratinib because of diarrhea was lower in both DE cohorts (DE1 3%;

DE2 6%) compared with ExteNET (17%).

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This approval was based on the results from our NALA trial.

Trials of Neratinib as a Single Agent .

In 2009, Pfizer Inc.

(“Pfizer”) presented data at the CTRC-AACR San Antonio Breast Cancer Symposium from a Phase II trial of neratinib administered as a single agent to patients with HER2-positive metastatic breast cancer.

Final results from this trial were published in the Journal of Clinical Oncology in March 2010.

The trial involved a total of 136 patients, 66 of whom had received prior treatment with trastuzumab and 70 of whom had not received prior treatment with trastuzumab.

The results of the study showed that neratinib was reasonably well-tolerated among both the pretreated patients and the patients who had not received prior treatment with trastuzumab.

Diarrhea was the most common side effect but was manageable with antidiarrheal agents and dose modification.

Efficacy results from the trial showed that the objective response rate was 24% for patients who had received prior trastuzumab treatment and 56% for patients with no prior trastuzumab treatment.

Furthermore, the median progression free survival (“PFS”) was 22.3 weeks for the patients who had received prior trastuzumab and 39.6 weeks for the patients who had not received prior trastuzumab.

Data from a second Phase II study, in which patients with confirmed HER2-positive metastatic breast cancer who had failed treatment with trastuzumab and taxane chemotherapy were given neratinib in combination with capecitabine, was presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.

The results of the study showed that the combination of neratinib and capecitabine had acceptable tolerability.

The efficacy results from the trial showed that for the 61 patients in the trial who had not been previously treated with the HER2 targeted anti-cancer drug lapatinib, there was an overall response rate of 64% and a clinical benefit rate of 72%.

In addition, for the seven patients in the trial who had previously been treated with lapatinib, there was an overall response rate of 57% and a clinical benefit rate of 71%.

The median PFS for patients who had not received prior treatment with lapatinib was 40.3 weeks and the median PFS for the patients who had received prior lapatinib treatment was 35.9 weeks.

In February 2013, we reached agreement with the FDA under a Special Protocol Assessment (“SPA”) for our Phase III clinical trial (PUMA-NER-1301 or the NALA trial) of neratinib in patients with HER2-positive metastatic breast cancer who have failed two or more prior treatments (third-line disease).

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The trial initially enrolled three cohorts of patients.

Patients in the second cohort (n=5) represent patients who had brain metastases which were amenable to surgery and who were administered neratinib monotherapy prior to and after surgical resection.

Patients in the second cohort (n=5) represent patients who had brain metastases that were amenable to surgery and who were administered neratinib monotherapy prior to and after surgical resection.

The third cohort (target enrollment=60) enrolled two sub-groups of patients (prior lapatinib-treated and no prior lapatinib) with progressive brain metastases who were administered neratinib in combination with the chemotherapy drug capecitabine.

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Overall, the most frequently observed adverse event was diarrhea, grade 2 (32%) and grade 3 (23%).

In April 2018, we announced that NERLYNX has been included as a recommended treatment option in the latest NCCN Clinical Practice Guidelines in Oncology Central Nervous System Cancers for patients with breast cancer and brain metastases.

In April 2018, we announced that NERLYNX has been included as a recommended treatment option in the latest NCCN Clinical Practice Guidelines in Oncology Central Nervous System Cancers (“CNS Guidelines”) for patients with breast cancer and brain metastases.

The NCCN designated NERLYNX in combination with capecitabine as a category 2A treatment option and NERLYNX in combination with paclitaxel as a category 2B treatment option.

Use of NERLYNX for breast cancer patients with brain metastases is outside the FDA-approved indication for NERLYNX and considered investigational, and we do not market or promote NERLYNX for these uses.

Based upon data from the TBCRC 022 study, NERLYNX plus KADCYLA (T-DM1) was added in June 2025 to the NCCN CNS Guidelines for patients with HER2-positive breast cancer with brain metastases as a category 2A recommendation.

Neratinib — Other Potential Applications

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During 2023, we met with the FDA to discuss our alisertib clinical development plan in both proposed indications and discussed potential dosing schedules for alisertib.

Following comments from the FDA on the proposed clinical development plans, we initiated clinical trials for both small cell lung cancer and breast cancer in 2024 and are currently enrolling.

Following comments from the FDA on the proposed clin ical development plans, we initiated clinical trials for both small cell lung cancer and breast cancer in 2024 and completed enrollment in the breast cancer clinical trial in February 2026.

Alisertib in Small Cell Lung Cancer

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These included small cell lung cancer as well as breast cancer.

In small cell lung cancer, the study design involved the administration of alisertib to patients with small cell lung cancer who had previously received up to two prior cytotoxic regimens in the metastatic setting.

In small cell lung cancer, the study design involved the administration of alisertib to patients who had previously received up to two prior cytotoxic regimens in the metastatic setting.

Patients were administered alisertib monotherapy at a dose of 50 mg twice a day (“BID”) for seven days followed by a 14-day break.

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The protocol was corrected approximately midway through the trial to correct the stratification definition of relapse type after primary treatment so that relapses were recorded “from last administration of platinum-based chemotherapy,” which is in line with the NCCN treatment guidelines and clinical treatment practice rather than “from initial response.” To maintain balance, the primary end point of PFS was analyzed by using the original stratification definition of relapse type.

However, a sensitivity analysis which used the corrected stratification definition was also performed.

However, a sensitivity analysis that used the corrected stratification definition was also performed.

The trial also incorporated an extensive biomarker analysis with a prespecified analysis of c-Myc expression an d an exploratory, retrospectiv e analysis of genetic alterations in circulating tumor DNA (“ctDNA”) with clinical outcome.

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Development plan.

In the United States the incidence of small cell lung cancer is approximately 31,000 to 33,000 patients per year with approximately 17,000 to 18,000 deaths per year.

There are two biomarkers of interest, c-Myc amplifications and RB1 mutations/deletions, that we intend to study with alisertib based on the previous clinical trial results which may provide differentiation from the other drugs in development.

According to the published biomarker data from the alisertib clinical trial, approximately 72% of small cell lung cancer patient samples had c-Myc amplifications and approximately 60-80% of small cell lung cancer patient samples had RB1 mutations.

In the United States, approximately 31,000 to 33,000 individuals are newly diagnosed with small cell lung cancer each year and approximately 16,000 to 17,000 patients die from the disease annually.

There are two biomarkers of interest, c-Myc expression and RB1 mutations, that we intend to study with alisertib based on prior clinical trial results which may provide differentiation from other drugs in development.

According to published biomarker data from an alisertib clinical trial, approximately 72% of samples from patients with small cell lung cancer had c-Myc expression and approximately 60-80% had RB1 mutations.

In August 2023, we announced that we had been notified by the FDA that we can proceed under our Investigational New Drug application (“IND”) with the clinical development of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer.

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In February 2024 we announced that we initiated the Phase II ALISCA TM -Lung1 trial.

This study is ongoing and actively recruiting.

This trial was amended in August 2025 to evaluate a higher dose of 60mg BID.

This study is ongoing and actively recruiting patients.

The primary endpoint of the trial is objective response rate with secondary endpoints of duration of response, disease control rate, PFS and overall survival.

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The primary efficacy end points include objective response rate, duration of response, disease control rate and PFS.

As a secondary objective, we will evaluate each of these efficacy endpoints within biomarker subgroups in order to determine whether any biomarker subgroup correlates with more favorable efficacy results, such as through observed in preclinical and clinical studies in other cancers including breast cancer and small cell lung cancer.

As a secondary objective, we will evaluate each of these efficacy endpoints within biomarker subgroups in order to determine whether any biomarker subgroup correlates with more favorable efficacy results, such as those observed in preclinical and clinical studies in other cancers including breast cancer and small cell lung cancer.

Pending the outcome of this study, we may then look to focus the future clinical development of alisertib in combination with endocrine therapy for patients with HER2-negative, hormone receptor-positive breast cancer in patients with any potential biomarkers.

Based on our interactions with the FDA, we believe that this trial design could find the optimal dose of alisertib in combination with endocrine therapy in patients with HER2-negative, hormone receptor-positive metastatic breast cancer, and pending sufficiently positive results, allow us to move into a pivotal Phase III trial.

Once the optimal alisertib dose is identified, we plan to engage with global regulatory agencies regarding the design of a pivotal Phase III trial, which we anticipate will be a randomized trial of alisertib plus investigator’s choice endocrine therapy versus placebo plus investigator’s choice endocrine therapy in patients with chemotherapy naïve HER2-negative, hormone receptor-positive metastatic breast cancer.

The trial was designed to enroll a to tal of 150 patients, which was achieved in February 2026.

Due to the larger number of patients in screening, we anticipate that the trial will enroll more than 150 patients.

Clinical Testing of Our Drug Candidates

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We have faced and will likely continue to face considerable competition from major pharmaceutical, biotechnology and specialty cancer companies.

Our competitors include, but are not limited to, Genentech, Novartis, Roche, Boehringer Ingelheim, Lilly, Amgen, Daiichi Sankyo, Jazz and Seagen.

Amgen, Daiichi Sankyo and Jazz are developing their drugs for the treatment of small cell lung cancer.

All of the other competitors are developing their drugs for the treatment of early stage and/or metastatic HER2-positive breast cancer and/or for cancers that have a HER2 mutation.

We are aware of the DESTINY-Breast11 neoadjuvant trial and DESTINY-Breast05 adjuvant trial of trastuzumab deruxtecan in early stage HER2-positive breast cancer, as well as the CompassHER2 RD trial of tucatinib in early stage HER2-positive breast cancer.

Our competitors include, but are not limited to, Genentech, Novartis, Roche, Boehringer Ingelheim, Lilly, Merck, AbbVie, Pfizer, Amgen, Daiichi Sankyo, Jazz and Seagen.

Merck, AbbVie, Amgen, Daiichi Sankyo and Jazz are developing their drugs for the treatment of small cell lung cancer.

All of the other competitors are developing their drugs for the treatment of early stage and/or metastatic HER2-positive breast cancer and/or for cancers that have a HER2 mutation or HER2-negative, hormone receptor-positive metastatic breast cancer.

We are aware of the results of the DESTINY-Breast11 neoadjuvant trial, which showed that trastuzumab deruxtecan significantly increased pathologic complete response rates over standard therapy.

We are also aware of the results of the DESTINY-Breast05 adjuvant trial of trastuzumab deruxtecan in early stage HER2-positive breast cancer, which showed that trastuzumab deruxtecan reduced the risk of disease recurrence or death in patients with high-risk HER2-positive early breast cancer following neoadjuvant therapy.

Lastly, we are aware of the CompassHER2 RD trial of tucatinib in early stage HER2-positive breast cancer.

In addition, we are also competing with academic institutions, governmental agencies and private organizations that are conducting research in the field of cancer.

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United States

We currently have an oncology sales force in the United States comprised of approximately 35 sales specialists, three clinical nurse educators, two strategic account managers and one national account director who are focused on promoting NERLYNX to oncologists and the oncology care team.

This sales force is supported by an experienced leadership team consisting of six regional business leaders and a VP of sales.

We currently have an oncology sales force in the United States comprised of approximately 35 sales specialists, four clinical nurse educators, five strategic account managers and one national strategic account director who are focused on promoting NERLYNX to oncologists and the oncology care team.

This sales force is supported by an experienced leadership team consisting of five regional business leaders, a Senior Vice President of Sales and a Senior Vice President of Marketing.

In addition, the broader commercial team is comprised of experienced professionals in marketing, training, sales operations, global product strategy as well as access and reimbursement.

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We launched NERLYNX in the United States in July 2017 with the goal of establishing NERLYNX as the standard of care for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer to follow adjuvant trastuzumab-based therapy.

In Feb 2020, NERLYNX was also approved in the United States in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.

In February 2020, NERLYNX was also approved in the United States in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.

We believe that the key commercial priorities for NERLYNX include:

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In the United States, we sell our products through a specialty pharmacy network and special distributor network.

The specialty pharmacy network sells directly to patients and consists of Acaria Health, Accredo, CVS, ONCO 360, Optum and Biologics.

Our specialty distributor network sells to hospitals, physician practices and other sites of care and consists of McKesson, ASD/Oncology Supply, Cardinal Health and DMS Pharmaceutical Group.

The specialty pharmacy network sells directly to patients and consists of Accredo, CVS, ONCO 360, Optum and Biologics.

Our specialty distributor network sells to hospitals, physician practices and other sites of care and consists of McKesson, ASD/Oncology Supply, Cardinal Health, DMS Pharmaceutical Group and Bio Care.

International

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In 2018, the EC granted a marketing authorization for NERLYNX in the EU for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who completed adjuvant trastuzumab-based therapy less than one year ago.

In December 2021, NERLYNX (neratinib) was included in the updated National Reimbursement Drug List (“NRDL”) by the China National Healthcare Security Administration for patients with early stage hormone receptor positive HER2-overexpressed/amplified breast cancer after adjuvant trastuzumab based therapy.

In December 2021, NERLYNX was included in the updated National Reimbursement Drug List (“NRDL”) by the China National Healthcare Security Administration for patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer after adjuvant trastuzumab based therapy.

The addition of NERLYNX to the China NRDL now enables broad access to neratinib to more women throughout China.

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We hold a worldwide exclusive license under our license agreement with Pfizer, as amended (the “Pfizer Agreement”) to 21 granted U.S.

patents and three pending U.S.

patents and one pending U.S.

patent applications, as well as foreign counterparts thereof, and other patent applications and patents claiming priority therefrom to develop and commercialize certain compounds, including neratinib.

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We also have a license to an issued U.S.

patent for the use of neratinib in the treatment of breast cancer, which is currently set to expire on October 8, 2025, an issued patent for the use of neratinib in the extended adjuvant treatment of early stage HER2-positive breast cancer that has previously been treated with a trastuzumab containing regimen that expires in 2030, two issued patents for the use of neratinib in combination with capecitabine, the latter of which is set to expire in 2031, and two issued patents for the formulation of NERLYNX® that are set to expire in 2030, two issued patents for the polymorphic forms of neratinib which are set to expire in 2028, one issued patent for the preparation of the polymorphic forms of neratinib which is set to expire in 2028, and three issued patents for the use of the polymorphic forms of neratinib in the treatment of breast cancer which are set to expire in 2028.

patent for the use of neratinib in the extended adjuvant treatment of early stage HER2-positive breast cancer that has previously been treated with a trastuzumab containing regimen that expires in 2030, two issued patents for the use of neratinib in combination with capecitabine, the latter of which is set to expire in 2031, and two issued patents for the formulation of NERLYNX® that are set to expire in 2030;

two issued patents for the polymorphic forms of neratinib which are set to expire in 2028;

one issued patent for the preparation of the polymorphic forms of neratinib which is set to expire in 2028;

and three issued patents for the use of the polymorphic forms of neratinib in the treatment of breast cancer which are set to expire in 2028.

In jurisdictions which permit such, we will seek patent term extensions where possible for certain of our patents (discussed further below, including in “Government Regulation”).

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The opposition was rejected as inadmissible by the Board of Appeal of the European Patent Office on December 1, 2020, and the EP1848414 patent was upheld as originally granted.

We have filed Supplemental Protection Certificate applications in the countries the EP1848414 patent was validated.

Of these Supplemental Protection Certificate applications, seven have been granted, one is undergoing appeal proceedings, six have been abandoned, five proceedings have been stayed, and the remaining six are in active prosecution.

We have filed Supplemental Protection Certificate applications in the countries where the EP1848414 patent was validated.

Of these Supplemental Protection Certificate applications, seven have been granted, two are undergoing appeal proceedings, ten have been abandoned, two proceedings have been stayed, and the remaining four are in active prosecution.

An opposition was filed by Hexal AG (“Hexal”) on August 3, 2016 against European Patent No.

EP2416774, which was licensed from Pfizer in 2011, and which claims neratinib for use in a method for treating HER-2/neu overexpressed/amplified cancer and improving IDFS, wherein the method comprises delivering neratinib therapy to HER-2/neu overexpressed/amplified cancer patients following the completion of at least one year of trastuzumab adjuvant therapy, and wherein the neratinib therapy comprises treating the cancer patients with neratinib for at least twelve months.

An oral hearing was held December 8, 2017, wherein the patent was maintained as granted.

An oral hearing was held on December 8, 2017, wherein the patent was maintained as granted.

Following an appeal filed by Hexal, the Board of Appeal of the European Patent Office rejected the claims as granted and all pending auxiliary requests during the oral hearing of September 2, 2021.

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One European divisional application, namely EP15188350.1, was granted with the European patent number EP3000467 on March 1, 2023.

Oppositions against EP3000467 were filed by Hexal AG (“Hexal”) on November 3, 2023, by Alfred E.

Oppositions against EP3000467 were filed by Hexal on November 3, 2023, by Alfred E.

Tiefenbacher (GmbH & Co.

KG) on November 28, 2023 and by Generics (UK) Limited (“Generics”) on December 1, 2023.

EP3000467 is used as the basic patent for Supplementary Protection Certificate applications for the EMA-approved NERLYNX® product, 17 of which have been granted, three proceedings have been stayed, and eleven are in active prosecution.

EP3000467 is used as the basic patent for Supplementary Protection Certificate applications for the EMA-approved NERLYNX® product, of which 18 have been granted, three proceedings have been stayed, and 10 are in active prosecution.

The patentee response to the notice of opposition was filed on April 15, 2024, following which, all three opponents filed additional arguments in reply to the patentee’s submission.

On February 6, 2025, we filed our response to the summons to attend oral proceedings.

Oral proceedings are currently scheduled for April 9, 2025.

On February 6, 2025, we filed our response to the summons to attend oral proceedings, including six auxiliary requests.

Tiefenbacher and Hexal AG filed their responses to the summons to oral proceedings on February 6 and 7, 2025, respectively.

Hexal filed a further brief on March 19, 2025.

Oral proceedings took place on April 9 and 10, 2025.

EP3000467 was upheld as amended after the first instance hearing based on Auxiliary Request 1, which covers the EMA approved indication for NERLYNX® as an extended adjuvant therapy for treating early-stage hormone receptor-positive HER-2-overexpressed/amplified breast cancer.

The first instance decision may be appealed.

Hexal filed an appeal on June 6, 2025, Generics filed an appeal on June 20, 2025 and Wyeth filed an appeal on June 30, 2025.

On September 5, 2025, Wyeth filed its grounds of appeal, including nine auxiliary requests.

One the same day, Hexal filed its grounds of appeal.

Generics filed its grounds of appeal on September 4, 2025, and Alfred E.

Tiefenbacher filed its grounds of appeal on September 1, 2025.

On December 16, 2025, Alfred E.

Tiefenbacher withdrew its appeal.

Wyeth responded to the opponents’ grounds of appeal on January 12, 2026.

One European divisional application is pending in the same family, namely EP 23157078.8.

A response to the European Search Opinion (“ESO”) for this application was filed February 14, 2024.

The first office action was issued on January 28, 2025 with a response to the first office action filed on July 22, 2025.

On October 6, 2017, Hexal also filed an opposition against European Patent No.

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On December 19, 2024, Sandoz AG requested the opposition division to delay issuance of their preliminary opinion by two months since they intend to respond to the patentee’s submission.

Oral proceedings are scheduled for April 16, 2026.

The patentee filed its written submission on February 16, 2026.

A divisional application, EP23206402.2, remains pending in this family.

Substantive examination has commenced and a response to the European Search Opinion (ESO) is due by May 20, 2025.

Substantive examination has commenced and a response to the European Search Opinion (ESO) was filed on May 20, 2025.

On May 21, 2020, Dr.

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In July 2021, we entered into a confirmatory agreement with Pfizer and Wyeth LLC (“Wyeth”), confirming that the rights granted to us by Pfizer under the Pfizer Agreement included Wyeth's rights in neratinib (oral), neratinib (intravenous), PB357, and certain related compounds.

As consideration for the license, we are required to make payments totaling $187.5 million upon the achievements of certain milestones if all such milestones are achieved.

FDA approval of NERLYNX in July 2017 triggered a one-time milestone payment.

In June 2020, we entered into a letter agreement (the “Letter Agreement”) with Pfizer relating to the method of payment associated with a one-time milestone payment under the Pfizer Agreement.

The Letter Agreement permits us to make the milestone payment in installments with portions of the amount payable to Pfizer (including interest) made in June and November 2020 for approximately $20.6 million in the aggregate and the remaining portion to be made in September 2021 for approximately $21.9 million.

Unpaid portions of the milestone payment accrued interest at 6.25% per annum until paid.

The installment payments and accrued interest are included in accrued in-licensed rights on the accompanying consolidated balance sheets.

As consideration for the license, we are required to make payments upon the achievement of certain milestones totaling approximately $187.5 million if all such milestones are achieved.

In connection with the FDA approval of NERLYNX in July 2017, we triggered a one-time milestone payment pursuant to the agreement.

In June 2020, we entered into a letter agreement (the “Letter Agreement”) with Pfizer relating to the method of payment associated with a one-time milestone payment under the license agreement with Pfizer.

The Letter Agreement permitted us to make the milestone payment in installments with the remaining amount payable to Pfizer (including interest).

The milestone payment accrued interest at 6.25% per annum.

The milestone payment including accrued interest of $1.8 million was paid in full in September 2021.

In addition, we reached a commercial milestone by achieving aggregate worldwide net sales of $250.0 million in calendar year 2022 , resulting in a payment to Pfizer of $12.5 million during the three months ended March 31, 2023.

We capitalized the milestones as intangible assets and are amortizing the assets to cost of sales on a straight-line basis over the estimated useful life of the licensed patent through 2030.

Should we commercialize additional compounds licensed from Pfizer or any products containing any of these compounds, we will be obligated to pay Pfizer annual royalties at a fixed rate in the low-to-mid teens of net sales of all such products, subject to certain reductions and offsets in some circumstances.

Our royalty obligation continues on a product-by-product and country-by-country basis, until the later of (1) the last to expire licensed patent covering the applicable licensed product in such country, or (2) the earlier of generic competition for such licensed product reaching a certain level in such country or expiration of a certain time period after first commercial sale of such licensed product in such country.

In the event that we sub-license the rights granted to us under the license agreement with Pfizer to a third party, the same milestone and royalty payments are required.

We can terminate the license agreement at will, or for safety concerns, in each case upon specified advance notice.

The Pfizer Agreement originally stipulated that should we commercialize any of the compounds licensed from Pfizer or any products containing any of these compounds, we will be obligated to pay to Pfizer incremental annual royalties between approximately 10% and 20% of net sales of all such products, subject, in some circumstances, to certain reductions.

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Because the following is only a summary, it does not contain all of the information that may be important to you.

For a complete description, you should refer to each of these agreements, copies of which have been filed as exhibits to this Annual Report on Form 10-K.

For a complete description, you should refer to each of these agreements, copies of which have been filed as exhibits to this Annual Report.

Specialised Therapeutics Agreement

On November 20, 2017, we entered into a sub-license agreement (the “Specialised Therapeutics Agreement”) with Specialised Therapeutics Asia Pte Ltd.

Pursuant to the Specialised Therapeutics Agreement, we granted to STA, under certain of our intellectual property rights relating to neratinib, an exclusive, sublicensable (under certain circumstances) license to commercialize any pharmaceutical product containing neratinib in finished form for the extended adjuvant treatment of patients with early stage HER2-positive breast cancer and HER2-positive metastatic breast cancer in Australia, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, New Zealand, Papua New Guinea, Philippines, Singapore, Thailand, Timor-Leste and Vietnam, or the STA Territory.

The Specialised Therapeutics Agreement sets forth the parties’ respective obligations with respect to the development, commercialization, and supply of the licensed product.

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On March 29, 2019, we entered into a sub-license agreement (the “Pierre Fabre Agreement”), with Pierre Fabre Medicament SAS (“Pierre Fabre”).

Pursuant to the Pierre Fabre Agreement, we granted to Pierre Fabre under certain of our intellectual property rights relating to neratinib an exclusive, sub-licensable (under certain circumstances) license to develop, manufacture and commercialize any pharmaceutical product containing neratinib for therapeutic and prophylactic indications for human or veterinary use in European countries excluding Russia and Ukraine, along with countries in North Africa and francophone countries of West Africa (the “Pierre Fabre Territory”).

Pursuant to the Pierre Fabre Agreement, we granted to Pierre Fabre under certain of our intellectual property rights relating to neratinib an exclusive, sub-licensable (under certain circumstances) license to develop, manufacture and commercialize any pharmaceutical product containing neratinib for therapeutic and prophylactic indications for human or veterinary use in European countries (excluding Ukraine), along with countries in North Africa and francophone countries of West Africa (the “Pierre Fabre Territory”).

On November 25, 2019, we entered into a license amendment (the “First Pierre Fabre Amendment”), with Pierre Fabre to extend the Pierre Fabre Territory to the Middle East, South Africa, Sudan and Turkey (as extended, the “First Pierre Fabre Territory”).

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Pursuant to the Pierre Fabre Agreement, we received an upfront payment and will potentially receive additional regulatory and sales-based milestone payments based on regulatory and sales activities in the Licensee Territory (as such term is defined in the Third Pierre Fabre Amendment).

Pursuant to the Third Pierre Fabre Amendment, we received an upfront payme nt of $50.0 million an d will potentially receive additional regulatory and sales-based milestone payments u p to $240.0 million based sole ly on regulatory and sales activities in the Third Pierre Fabre Territory.

In addition, we will receive double-digit royalties based on net sales of the licensed products in the Licensee Territory, on the one hand, and double-digit royalties based on net sales of the licensed products in the Third Pierre Fabre Territory, on the other hand.

Pursuant to the Third Pierre Fabre Amendment, we received an upfront payment of $50.0 million and will potentially receive additional regulatory and sales-based milestone payments up to $240.0 million based solely on regulatory and sales activities in the Third Pierre Fabre Territory.

In addition, we will receive double-digit royalties based on net sales of the licensed products in the Licensee Territory, and double-digit royalties based on net sales of the licensed products in the Third Pierre Fabre Territory.

For the purposes of calculating royalties, sales of the licensed products in the Third Pierre Fabre Territory will be excluded from the sales of licensed products made in the Licensee Territory.

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

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

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

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

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

Orphan exclusivity also could block the approval of a competing product for seven years if a competitor obtains approval of the “same drug,” as defined by the FDA, or if a drug candidate is determined to be contained within the competitor’s product for the same disease or condition.

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

Orphan exclusivity also could block the approval of a competing product for seven years if a competitor obtains approval of the “same drug,” as defined by the FDA with respect to the relevant indication or use, or if a drug candidate is determined to be contained within a competitor’s product approved for the same indication or use.

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

Expedited Review and Approval Programs .

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In order to market our drug candidates in the EU and many other foreign jurisdictions, we must obtain separate regulatory approvals.

More concretely, in the EU, medicinal drug candidates can only be placed on the market after obtaining a MA.

More concretely, in the EU, medicinal drug candidates can only be placed on the market after obtaining an MA.

To obtain regulatory approval of a product candidate under EU regulatory systems, we must submit an MAA.

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The centralized procedure is mandatory for certain types of products, such as (i) medicinal products, derived from biotechnology processes, such as genetic engineering, (ii) designated orphan medicinal products, (iii) advanced therapy medicinal products (“ATMPs”) such as gene therapy, somatic cell therapy or tissue-engineered medicines, and (iv) medicinal products containing a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto-immune and other immune dysfunctions and viral diseases.

The centralized procedure is optional for products containing a new active substance not yet authorized in the EU or for drug candidates which constitute a significant therapeutic, scientific or technical innovation, or for which the granting of an MA would be in the interest of public health in the EU.

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

“National MAs” – are issued by the competent authorities of the EU member states, and only cover their respective territory and are available for drug candidates not falling within the mandatory scope of the centralized procedure.

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A medicinal product can be designated as an orphan if its sponsor can establish that:

(1) the product is intended for the diagnosis, prevention or treatment of a life threatening or chronically debilitating condition (2) either (a) such condition affects not more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from the orphan status, would not generate sufficient return in the EU to justify the necessary investment;

and (3) there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized for marketing in the EU or, if such method exists, the product will be of significant benefit to those affected by that condition.

(i) the product is intended for the diagnosis, prevention or treatment of a life threatening or chronically debilitating condition (ii) either (a) such condition affects not more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from the orphan status, would not generate sufficient return in the EU to justify the necessary investment;

and (iii) there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized for marketing in the EU or, if such method exists, the product will be of significant benefit to those affected by that condition.

Orphan designation must be requested before submitting an MAA.

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Following the end of the Brexit transition period on January 1, 2021, and the implementation of the Windsor Framework on January 1, 2025, the United Kingdom (“UK”) is not generally subject to EU laws in respect of medicines.

The EU laws that have been transposed into United Kingdom law through secondary legislation remain applicable in the UK;

however, new legislation such as the (EU) CTR is not applicable in Great Britain.

The EU laws that have been transposed into UK law through secondary legislation remain applicable in the UK;

however, new legislation such as the (EU) CTR is not applicable in the UK.

Under the Medicines and Medical Devices Act 2021, the Secretary of State or an ‘appropriate authority’ has delegated powers to amend or supplement existing regulations in the area of medicinal products and medical devices.

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The UK regulatory framework in relation to clinical trials is governed by the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended, which is derived from existing EU legislation (as implemented into UK law, through secondary legislation).

On January 17, 2022, the MHRA launched an eight-week consultation on reframing the UK legislation for clinical trials which aimed to streamline clinical trials approvals, enable innovation, enhance clinical trials transparency, enable greater risk proportionality, and promote patient and public involvement in clinical trials.

The MHRA published its consultation outcome on March 21, 2023, confirming that it would bring forward changes to the legislation.

The resulting legislative amendments, which are yet to be published, will ultimately determine the extent to which the UK clinical trials framework aligns with or diverges from the (EU) CTR.

In October 2023, the MHRA announced a new Notification Scheme for clinical trials which enables a more streamlined and risk-proportionate approach to initial clinical trial applications for Phase 4 and low-risk Phase 3 CTAs.

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

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

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

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The MHRA has introduced changes to national licensing procedures, including procedures to prioritize access to new medicines that will benefit patients, a 150-day assessment (subject to clock-stops) and a rolling review procedure.

In addition, since January 1, 2024, the MHRA may rely on the International Recognition Procedure, or IRP, when reviewing certain types of MAAs.

In addition, since January 1, 2024, the MHRA may rely on the International Recognition Procedure (“IRP”), when reviewing certain types of MAAs.

Pursuant to the IRP, the MHRA will take into account the expertise and decision-making of trusted regulatory partners (e.g., the regulatory authorities in Australia, Canada, Switzerland, Singapore, Japan, the United States.

The MHRA will conduct a targeted assessment of IRP applications but retain the authority to reject applications if the evidence provided is considered insufficiently robust.

The IRP allows medicinal products approved by such trusted regulatory partners that meet certain criteria to undergo a fast-tracked MHRA review to obtain and/or update an MA in the UK or Great Britain.

The IRP allows medicinal products approved by such trusted regulatory partners that meet certain criteria to undergo a fast-tracked MHRA review to obtain and/or update an MA in the UK.

Applications should be decided within a maximum of 60 days if there are no major objections identified that cannot be resolved within such 60-day period and the approval from the trusted regulatory partner selected has been granted within the previous two years or if there are such major objections identified or such approval hasn’t been granted within the previous two years within 110 days.

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In the UK, the initial duration of an MA is five years and following renewal will be valid for an unlimited period unless the MHRA decides on justified grounds relating to pharmacovigilance to proceed with only one additional five-year renewal.

Any authorization which is not followed by the actual placing of the drug on the market in the UK within three years shall ease to be in force.

Any authorization which is not followed by the actual placing of the drug on the market in the UK within three years shall cease to be in force.

There is no pre-MA orphan designation in the UK.

Instead, the MHRA reviews applications for orphan designation in parallel to the corresponding MA application.

The criteria are essentially the same, but have been tailored for the market, i.e., the prevalence of the condition in GB, rather than the EU, must not be more than five in 10,000.

Should an orphan designation be granted, the period or market exclusivity will be set from the date of first approval of the product in GB.

The criteria are essentially the same, but have been tailored for the market, i.e., the prevalence of the condition in the UK, rather than the EU, must not be more than five in 10,000.

Should an orphan designation be granted, the period or market exclusivity will be set from the date of first approval of the product in the UK.

If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Coverage and Reimbursement

In the United States and internationally, sales of NERLYNX and any other product(s) that we market in the future, and our ability to generate revenues on such sales, are dependent, in significant part, on the availability of adequate coverage and reimbursement from third-party payors, such as state and federal governments, managed care providers and private insurance plans.

In the United States and internationally, sales of NERLYNX and any other products that we market in the future, and our ability to generate revenues on such sales, are dependent, in significant part, on the availability of adequate coverage and reimbursement from third-party payors, such as state and federal governments, managed care providers and private insurance plans.

Private insurers, such as health maintenance organizations and managed care providers, have implemented cost-cutting and reimbursement initiatives and likely will continue to do so in the future.

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In addition, in some countries, cross border imports from low‑priced markets exert a commercial pressure on pricing within a country.

Historically, products launched in the European Union do not follow price structures of the United States and generally prices tend to be significantly lower.

In addition, particularly in the United States and increasingly in other countries, we are required to provide discounts and pay rebates to state and federal governments and agencies in connection with purchases of our products that are reimbursed by such entities.

Historically, products launched in the EU do not follow price structures of the United States and generally prices tend to be significantly lower.

In addition, particularly in the United States and increasingly in other countries, we are required to provide discounts and pay rebates under federal programs we participate in.

For example, we pay rebates under the Medicaid Drug Rebate Program (“MDRP”) and offer discounts under the 340B drug pricing program in order for reimbursement to be available for our products.

It is possible that future legislation in the United States and other jurisdictions could be enacted to potentially impact reimbursement rates for the products we are developing and may develop in the future.

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There have been, and we expect there will continue to be, legislative and regulatory proposals to change the healthcare system in ways that could significantly affect our future business.

For example, the Patient Protection and Affordable Care Act (the “ACA”), enacted in March 2010, substantially changed the way healthcare is financed by both governmental and private insurers.

Among other provisions, the ACA included an annual, nondeductible fee on any entity that manufactures or imports certain branded prescription drugs and biologic agents and a new formula that increases the rebates a manufacturer must pay under the Medicaid Drug Rebate Program.

For example, the Affordable Care Act (the “ACA”) was enacted in 2010 and substantially changed the way healthcare is financed by both governmental and private insurers.

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

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

Most significantly, in August 2022, President Biden signed the Inflation Reduction Act of 2022 (“IRA”) into law.

Most significantly, the Inflation Reduction Act (“IRA”) was enacted in 2022.

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

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

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

CMS has published the negotiated prices for the initial 10 drugs, which will first be effective in 2026, and has published the list of the subsequent 15 drugs that will be subject to negotiation.

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

Centers for Medicare & Medicaid Services (“CMS”) has published the negotiated prices for the initial 10 drugs, which went into effect in January 2026, and the subsequent 15 drugs, which will first be effective in 2027.

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

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

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

Under the IRA manufacturer discount program that replaced the coverage gap discount program as of January 1, 2025, manufacturers must give a 10 percent discount on Part D drugs in the initial coverage phase, and a 20 percent discount on Part D drugs in the so-called “catastrophic phase” (the phase after the patient incurs costs above the initial phase out-of-pocket threshold, which will be $2,000 beginning in 2025).

The IRA allows the 10 and 20 percent discounts to be phased in over time for certain drugs for “specified manufacturers.” In April 2024, CMS informed us that we are deemed a specified small manufacturer and the discount will be phased in over several years and will increase over time.

We are continuing to evaluate the potential impact of this status on our future revenues.

NERLYNX is reimbursed under Medicare Part D, and the reimbursement amount will be impacted by the 10 and 20 percent discounts under the IRA’s new discounting program (as noted above).

NERLYNX is reimbursed under Medicare Part D, and we have incurred IRA inflation rebates.

We may incur additional Part D inflation rebates in subsequent periods.

Such rebate liability could be significant.

The reimbursement amount for NERLYNX under Medicare Part D will be impacted by the 10 and 20 percent discounts under the IRA’s new discounting program (as noted above).

We anticipate that these increased discounts will impact NERLYNX revenues over time, while also having an industry-wide impact on the patient out of pocket costs of Part D drugs.

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This may incentivize Part D prescription drug plans to seek greater price concessions from us in order to include NERLYNX on their formularies.

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

Such reductions are expected to decrease the number of persons enrolled in Medicaid and reduce the services covered by Medicaid, which could adversely affect our sales of NERLYNX and any other product candidate that we commercialize.

The Trump administration is pursuing a two-fold strategy to reduce drug costs in the United States.

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

On the one hand, President Trump has threatened to impose significant tariffs on pharmaceutical manufacturers that do not adopt pricing policies such as most favored nation pricing, which would tie the price for drugs in the United States to the lowest price in a group of other countries.

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

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

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

Imposing a rebate in the United States that is based on drug prices outside the United States would mark a drastic and unprecedented shift in the United States pharmaceutical market, and while the impact of the Globe and Guard proposed regulations, if finalized, cannot yet be determined, it is likely to be significant.

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

pharmaceutical sector and our business.

The cost of prescription pharmaceuticals in the United States continues to be the subject of considerable discussion.

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In some cases, these actions have been designed to encourage importation from other countries and bulk purchasing.

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

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

Similar political, economic and regulatory developments are occurring in the EU and may affect the ability of pharmaceutical companies to profitably commercialize their products.

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Medicare is a federal program covering individuals aged 65 and over as well as those with certain disabilities.

As a condition of having federal funds being made available for covered outpatient drugs under Medicaid and Medicare Part B, we have enrolled in the Medicaid Drug Rebate Program (“MDRP”), which requires us to pay a rebate to state Medicaid programs for each unit of our covered outpatient drugs dispensed to a Medicaid beneficiary and paid for by a state Medicaid program.

Medicaid rebates are based on pricing data that we must report on a monthly and quarterly basis to the U.S.

Centers for Medicare & Medicaid Services (“CMS”), the federal agency that administers the MDRP and Medicare programs.

As a condition of having federal funds being made available for covered outpatient drugs under Medicaid and Medicare Part B, we have enrolled in the MDRP, which requires us to pay a rebate to state Medicaid programs for each unit of our covered outpatient drugs dispensed to a Medicaid beneficiary and paid for by a state Medicaid program.

Medicaid rebates are based on pricing data that we must report on a monthly and quarterly basis to the CMS, the federal agency that administers the MDRP and Medicare programs.

For the MDRP, these data include the average manufacturer price (“AMP”) for each drug and, in the case of our innovator products, the best price (“BP”).

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As of December 31, 2025, our workforce consisted of 179 full-time employees.

Throughout 2024, the size of our employee population was fairly consistent, but ending with lower headcount at the end of the year due to reorganization/efficiency efforts and employee attrition.

Our employee population consists of a field-based commercial team, working from home offices and visiting customers across the country, employees aligned with our two offices in the United States - Los Angeles, California and South San Francisco, California – and the majority of non-field sales employees working remotely from home on a consistent basis.

For our office-based employees, during the latter part of 2022, we adopted a virtual work environment, allowing functional management and employees to determine when working virtually is more efficient and productive, and when in-office collaboration is beneficial.

Throughout 2025, the size of our employee population was fairly consistent, ending with headcount slightly higher at the end of the year due to additional positions being added in multiple functions and replacement positions which were open at the beginning of 2025 being filled.

Our largest employee population is the field-based commercial team, working from home offices and visiting customers in their territories.

Our second largest employee population is located in the greater Los Angeles area, aligned with our corporate headquarters in Los Angeles, California.

The majority of our non-field sales employees work remotely from home on a consistent basis.

We operate in a virtual work environment, allowing functional management and employees to determine when working virtually is more efficient and productive, and when in-office collaboration is beneficial.

This work model allows us to attract and hire employees from across the country, which contributes to increased employee engagement, satisfaction and retention.

We are an equal opportunity employer and believe strongly in hiring and maintaining a diverse, equitable and inclusive workforce.

This is reflected in our numbers with our total workforce being approxima tely 49% women and 37% eth nically diverse.

This is reflected in our numbers with our total workforce being approximately 46% women and 39% ethnically diverse.

The following table summarizes our workforce by location for the years ended December 31, 2025 and December 31, 2024:

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We believe that the safety and health of our employees and their families are essential to our business.

Our culture is driven by a desire to do what is right, and we strive to support the well-being of our employees.

Our goal is to support the well-being of our employees.

We believe that our employees and their families need to be healthy to be the most productive and engaged at work.

Our financial, health and wellness benefits are designed to assist employees with financial planning, preventative health care and support when unexpected circumstances arise.

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a Lifestyle Spending Account to support employee wellness and fitness activities;

programming, including hosting a company-wide “Wellness Week” and “Walking Challenges” to motivate employees to engage with each other for increased physical fitness opportunities;

programming, including on-demand and live “Wellness Breaks” facilitated by expert instructors online, and “Walking Challenges” to motivate employees to engage with each other for increased physical fitness opportunities;

ergonomic support in the form of training opportunities, 1:1 evaluations and providing ergonomically compatible equipment when necessary.

subsidies for mobile devices and internet access

Compensation & Benefits

We know that developing and keeping great people is a vital part of our competitive edge and essential to providing the best patient care.

For this reason, we offer a robust total compensation package in an effort to attract and engage high caliber employees.

Since 2019, we have offered personalized total compensation statements to all full-time employees.

These statements provide a transparent view of each employee’s monetary and non-monetary benefits.

Employee’s total compensation represents a broad spectrum of plans and programs designed to reward and motivate employees throughout their careers.

Our total rewards package consists of competitive market-based salaries and cash target bonuses.

Bonus opportunity and equity compensation increase as a percentage of total compensation based on level of responsibility with actual bonus payout based on performance.

In addition to competitive salaries and performance incentives, we offer employees 100% employer-paid benefits that include medical, dental, vision, mental health services, life insurance, paid time off and family leave, 401(k) match, fertility benefits, fitness/wellness benefits, volunteer days and more.

Our benefit programs are constantly evolving to meet our employees’ needs and renew our commitment to them as a vital resource to our continued success.

We know that attracting, developing and retaining the best employees is a critical part of our competitive edge, future success, and a key component to delivering the best care for patients.

We offer a competitive and robust total compensation package to maintain the most qualified employee population.

Our total rewards package consists of competitive salaries benchmarked to market data, cash bonuses and equity grants.

Bonus opportunities and equity compensation increase as a percentage of total compensation based on level of responsibility, with actual bonus payout based on performance.

In addition to competitive salaries and performance incentives, we offer employees 100% employer-paid premiums for medical, dental, vision, mental health services, and life insurance.

In addition, we offer a 401(k) plan with employer match, paid time off, various leave of absence options, fertility benefits, fitness/wellness benefits, volunteer days and more.

Our benefit programs are constantly evolving to meet our employees’ needs and are reviewed and modified each year as part of our commitment to employee wellness and success.

Total compensation represents a broad spectrum of plans and programs designed to reward and motivate employees throughout their careers at Puma.

Culture and Communication

How we conduct our business is just as important as what we do and achieve.

Our core values are the principles that guide our company strategy and our individual actions.

Our positive and supportive culture is continuously referenced by employees as a reason they enjoy working at Puma.

We maintain a work environment that is collaborative, friendly, supportive and encourages our employees to focus on patient outcomes as a key motivator.

We host employee events with medical and scientific presentations given by experts in the field, patient ambassadors, thought leaders and functional leaders to foster employee education.

At all times we strive to distinguish ourselves as a respected biopharmaceutical company that is differentiated by top talent and innovative products to enhance cancer care.

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The majority of our employees have obtained advanced degrees in their professions, and we support their continued development with individualized development plans and objectives, mentoring, coaching, training and conference attendance.

In addition, we offer an Educational Reimbursement Program to assist employees who want to further their educations.

In addition, we offer an Educational Reimbursement Program to assist employees who want to further their education.

Communication is critical in our ability to continuously enhance our company culture and create a more inclusive environment.

We conduct virtual town hall meetings to share information about our business activities, company performance, and other topics of interest to our employees.

We continue to publish a quarterly newsletter to share interesting and useful information through our involvement in cancer-related conferences and causes, such as Breast Cancer Awareness Month.

We also introduce new employees to the organization in our Welcome to Puma section, and profile existing employees in our Get Connected section, where we share information about their roles, motivations to be with Puma, backgrounds, and interests.

In addition, we include information about upcoming employee events and benefit opportunities, as well as previous events like employee team building and Wellness Week participation.

We conduct town hall meetings to share information with employees about what is happening across the business, and often include guest speakers, such as Patient Ambassadors, to motivate and inform our employees.

Lastly, the Human Resources function recently created an employee self-service portal to allow employees to find useful information quickly and easily without assistance.

Corporate Information and History

Our principal executive offices are located at 10880 Wilshire Boulevard, Suite 1700, Los Angeles, California 90024 and our telephone number is (424) 248-6500.

Our internet address is www.pumabiotechnology.com.

Our annual, quarterly and current reports, and any amendments to those reports, filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934 may be accessed free of charge through our website after we have electronically filed or furnished such material with the SEC.

Our internet address is https://www.pumabiotechnology.com.

Our annual, quarterly and current reports, and any amendments to those reports, filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act may be accessed free of charge through our website after we have electronically filed or furnished such material with the SEC.

We also make available free of charge on or through our website our Code of Business Conduct and Ethics, Corporate Governance Guidelines, Audit Committee Charter, Compensation Committee Charter, Nominating and Corporate Governance Committee Charter and Research and Development Committee Charter.

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Any amendment or waiver disclosed on our website will remain available on our website for at least 12 months after the initial disclosure.

The reference to www.pumabiotechnology.com (including any other reference to such address in this Annual Report) is an inactive textual reference only, meaning that the information contained on or accessible from the website is not part of this Annual Report on Form 10-K and is not incorporated in this report by reference.

The reference to https://www.pumabiotechnology.com (including any other reference to such address in this Annual Report) is an inactive textual reference only, meaning that the information contained on or accessible from the website is not part of this Annual Report and is not incorporated in this report by reference.

We were originally incorporated in the State of Delaware in April 2007 under the name Innovative Acquisitions Corp.

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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