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Item 1. Business

2026-02-23 compared with 2025-02-24 · 406 added, 271 removed, 481 unchanged (58% of the section changed)

Company Overview

Summit Therapeutics Inc.

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The Company’s pipeline of product candidates is designed with the goal to become the patient-friendly, new-era standard-of-care medicines, in the therapeutic area of oncology.

The Company’s current lead development candidate is ivonescimab, a novel, potential first-in-class bispecific antibody intending to combine the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects of an anti-VEGF compound into a single molecule.

On December 5, 2022, the Company entered into a Collaboration and License Agreement (the “License Agreement”) with Akeso, Inc.

and its affiliates (collectively, “Akeso”) pursuant to which the Company has in-licensed intellectual property related to ivonescimab.

On December 5, 2022, the Company entered into the License Agreement with Akeso, Inc.

and its affiliates (collectively, “Akeso”) pursuant to which the Company has in-licensed intellectual property rights related to ivonescimab (as amended, the “License Agreement”).

Through the License Agreement, the Company obtained the rights to develop and commercialize ivonescimab in the United States, Canada, Europe, and Japan.

The License Agreement and transaction closed in January 2023 following customary waiting periods.

On June 3, 2024, the Company entered into an amendment to the License Agreement with Akeso to expand its territories covered under the License Agreement to also include the Latin America, Middle East and Africa regions (collectively, and as expanded, the "Licensed Territory").

On June 3, 2024, the Company entered into the Second Amendment with Akeso to expand its territories covered under the License Agreement to also include Latin America, including Mexico and all countries in Central America and South America, the Middle East and Africa.

The Company’s operations are focused on the development of ivonescimab and other future activities, as the Company determines.

The Company has begun its development for ivonescimab in non-small cell lung cancer (“NSCLC”), specifically launching Phase III clinical trials in the following proposed indications:

(a) ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor (“EGFR”)-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (“TKI”) (“HARMONi”);

(b) ivonescimab combined with chemotherapy in first-line metastatic NSCLC patients (“HARMONi-3”).

In addition, the Company has begun to activate clinical trial sites in the United States for a Phase III clinical study in the following proposed indication:

The Company is developing ivonescimab in non-small cell lung cancer (“NSCLC”) and colorectal cancer (“CRC”), specifically conducting Phase III clinical trials in the following proposed indications:

(a) ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor (“EGFR”)-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR tyrosine kinase inhibitor (“TKI”) (“HARMONi”);

(b) ivonescimab combined with chemotherapy in patients with first-line metastatic NSCLC (including separate statistical analyses planned for patients with squamous NSCLC and non-squamous NSCLC) (“HARMONi-3”);

(c) ivonescimab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression (“HARMONi-7”);

(d) ivonescimab combined with chemotherapy in patients with first-line unresectable metastatic CRC (“HARMONi-GI3”).

In October 2024, the Company completed enrollment in its HARMONi clinical trial.

The Company expects to disclose topline results from HARMONi in mid-2025, depending upon maturation of the data per the protocol.

In May 2025, we announced topline results from our multiregional, double-blinded, placebo-controlled, Phase III study HARMONi.

At the prespecified primary data analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement in progression free survival (“PFS”), the magnitude of which we believe to be clinically meaningful, with a hazard ratio of 0.52 (95% CI:

p<0.00001) compared to placebo in combination with chemotherapy;

median PFS was 6.8 months for those patients receiving ivonescimab plus chemotherapy compared to 4.4 months for those receiving chemotherapy.

PFS was assessed by blinded independent central radiology committee (“BICR”).

We believe the PFS hazard ratio that was observed in both Asian and Western sub-populations to be clinically meaningful.

The primary analysis demonstrated the consistency of the magnitude of the PFS benefit between patients randomized in Asian and Western territories, as well as the consistency in a single-region study (HARMONi-A) with this multiregional study.

In a longer-term follow-up of PFS, which included all Western patients and at least six months of follow-up time for all patients, ivonescimab plus chemotherapy demonstrated a consistent improvement in PFS with an observed HR of 0.57 (95% CI:

0.46 – 0.71).

With the longer-term follow-up analysis, consistency of the magnitude of PFS benefit was demonstrated between patients randomized in Asia and Western patients when measured by hazard ratio.

This longer-term follow-up analysis of PFS was performed at the time of the primary overall survival (“OS”) analysis.

Ivonescimab in combination with chemotherapy showed a positive trend in OS in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI:

This trend provides further support for its use in 2L+ EGFRm NSCLC, a setting where high unmet need continues to exist with limited approved options in the United States and other western territories.

Currently, there are no FDA-approved regimens that have demonstrated a statistically significant OS benefit in this patient setting.

Both Asian and North American patients demonstrated a positive trend in OS.

The results of the primary analysis in this multiregional study were consistent with that of the single-region randomized Phase III HARMONi-A study, which demonstrated a statistically significant OS benefit with a hazard ratio of 0.74 in the primary OS analysis in a similar patient population.

In September 2025, an additional ad hoc OS analysis was performed for the HARMONi study whereby the Western patients were followed for a longer period of time (Asian patients were locked at the time of the primary analysis).

In this analysis that included longer-term follow-up of Western patients (median follow-up time of Western patients of 13.7 months), a hazard ratio consistent with the primary analysis was observed with an improved nominal p-value (HR=0.78;

nominal p=0.0332).

Median OS for this analysis remained the same in both arms as was observed in the primary analysis.

Median OS in Western patients receiving ivonescimab was 17.0 months compared to 14.0 months for those receiving placebo (HR=0.84);

median OS in North American patients, specifically, had not yet been reached in the ivonescimab arm compared to 14.0 months in the placebo arm (HR=0.70).

The hazard ratios for Western patients in totality, as well as patients from the North American and European regions individually, improved from the primary OS analysis to the analysis with longer-term follow-up of Western patients.

Consistent benefit was observed across pre-defined subgroups.

The dual primary endpoints were allocated separate alpha levels and tested individually.

The alpha was recycled from the PFS to the OS analysis upon the successful achievement of the PFS endpoint.

Based on the results of the HARMONi clinical trial, we submitted a BLA in the fourth quarter of 2025 to seek approval for ivonescimab plus chemotherapy for this proposed indication.

The positive results of the multiregional Phase III study are detailed further under “Product Pipeline” below.

As previously disclosed, the FDA noted that a statistically significant overall survival benefit is necessary to support marketing authorization in this setting.

After careful consideration of the safety and efficacy profile of the current FDA-approved options for patients in this setting, the positive results of the Phase III multiregional study, including regional consistency, as well as discussions with key opinion leaders and those physicians who have administered ivonescimab to patients in a clinical study setting, we believe that the safety and efficacy data generated in the HARMONi study demonstrates that the ivonescimab regimen offers a potential treatment option for patients impacted by EGFR-mutant NSCLC in this setting with a favorable benefit-risk profile despite the lack of a statistically significant overall survival benefit.

Summit announced in January 2026 that the FDA accepted for filing the BLA, seeking approval for ivonescimab in combination with chemotherapy for this proposed indication.

The FDA noted it intends to perform a complete review of the accepted and filed BLA, including planned mid-cycle and wrap-up meetings, and, subject to major deficiencies not being identified during the FDA’s review, proposed labeling, prior to the Prescription Drug User Fee Act goal action date of November 14, 2026.

Akeso Collaboration and License Agreement

Pursuant to the License Agreement with Akeso, the Company received the rights to develop and commercialize ivonescimab in the Licensed Territory.

Akeso will retain development and commercialization rights for the rest of the world excluding the Licensed Territory.

Pursuant to the License Agreement with Akeso, the Company received the rights to develop and commercialize ivonescimab in the United States, Canada, Europe, Japan, Latin America, Middle East and Africa regions (collectively, the “Licensed Territory”).

Akeso retained development and commercialization rights for the rest of the world excluding the Licensed Territory.

In exchange for these rights, Summit made an upfront payment during the first quarter of 2023 comprised of $474.9 million cash and the issuance of 10 million shares of Company common stock in lieu of $25.1 million cash pursuant to a share transfer agreement.

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In connection with the License Agreement, the Company agreed to purchase a certain portion of drug substance and/or drug product for clinical and commercial supply and to enter into a supply agreement with Akeso.

Pursuant to the terms of the License Agreement, Summit has final decision-making authority with respect to commercial strategy, pricing and reimbursement and other commercialization matters in the Licensed Territory.

Pursuant to the terms of the License Agreement, Summit has final decision-making authority with respect to all of its commercialization activities including, but not limited to, commercial strategy, pricing and reimbursement in the Licensed Territory.

Summit has not assumed any liabilities (including contingent liabilities), nor acquired any physical assets or trade names, or hired or acquired any employees from Akeso in connection with the License Agreement.

Ivonescimab is a novel potential first-in-class PD-1 / VEGF bispecific antibody, believed to be the most advanced in clinical development in the Licensed Territory.

Engineered with Akeso’s unique Tetrabody technology, ivonescimab, as a single molecule, blocks programmed cell death protein 1 (“PD-1”) from binding to PD-L1 and PD-L2, and blocks vascular endothelial growth factor (“VEGF”) from binding to VEGF receptors.

Ivonescimab is designed to potentially allow cooperative binding of the intended targets, such that the binding of PD-1 increases the binding affinity of VEGF.

Ivonescimab is a novel potential first-in-class PD-1 / VEGF-A bispecific antibody, believed to be the most advanced in clinical development in the Licensed Territory.

Engineered with Akeso’s unique Tetrabody technology, ivonescimab, as a single molecule, blocks programmed cell death protein 1 (“PD-1”) from binding to PD-L1 and PD-L2, and blocks the protein vascular endothelial growth factor-A (“VEGF”) from binding to VEGF receptors.

Ivonescimab is designed to potentially allow cooperative binding of the intended targets, such that the binding of VEGF increases the binding affinity of PD-1.

In view of the co-expression of VEGF and PD-1 in the tumor micro-environment (“TME”), ivonescimab may block these two pathways more effectively and enhance the antitumor activity, as compared to combination therapy through what is believed to be a unique cooperative binding mechanism.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the TME as compared to normal tissue in the body.

As shown in Akeso’s in-vitro studies, ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME with over 10 fold increased binding affinity to PD-1 in the presence of VEGF in vitro .

As shown in Akeso’s in-vitro studies, ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME with over 10-fold increased binding affinity to PD-1 in the presence of VEGF.

This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities has the potential to direct ivonescimab to the tumor tissue versus healthy tissue.

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Ivonescimab is currently being developed by both Akeso and the Company in multiple Phase III clinical trials.

There are also multiple early-phase trials being conducted in multiple solid tumors.

Ivonescimab has been dosed in more than 2,300 patients globally.

Akeso-Sponsored Ivonescimab Trials

Akeso is currently developing ivonescimab in non-small cell lung cancer and other solid tumor settings.

Ivonescimab is currently approved in China in combination with chemotherapy for patients with EGFR-mutated non-small cell lung cancer whose tumors have progressed following an EGFR-TKI based on the results of the HARMONi-A clinical trial that was first announced and presented in 2024.

In addition, a supplemental application has been submitted in China by Akeso for ivonescimab as monotherapy based on the results of the HARMONi-2 study in first-line, PD-L1 positive non-small cell lung cancer.

Further details related to these two trials, in addition to other Phase II clinical data presented during 2024, are described further below.

In addition, Akeso is currently conducting Phase III clinical trials in combination with chemotherapy in first-line advanced squamous NSCLC (HARMONi-6) and first-line biliary tract cancer (HARMONi-GI1), as well as in combination with ligufalimab, a proprietary Akeso-owned investigational CD-47 monoclonal antibody, in first-line recurrent / metastatic PD-L1

positive head-and-neck cancer (HARMONi-HN1).

Further, Akeso has announced its intention to conduct Phase III clinical trials in combination with chemotherapy in first-line advanced PD-L1 low or negative triple-negative breast cancer (HARMONi-BC1) and first-line advanced pancreatic cancer (HARMONi-GI2).

Based on data published by Akeso at the American Society of Clinical Oncology (ASCO 2024) and in a recent publication in the Journal of the American Medical Association (JAMA) in the HARMONi-A study, in a single-region (China), randomized, double-blinded Phase III study in patients with NSCLC who have progressed following an EGFR-TKI, ivonescimab achieved its primary endpoint of PFS when combined with doublet chemotherapy (pemetrexed and carboplatin).

Patients experienced a 54% reduction in disease progression or death as compared to placebo plus doublet-chemotherapy (HR:

0.46, 95% CI:

In a pre-specified subgroup analysis of patients who received a previous third-generation TKI, a hazard ratio of 0.48 was observed.

A median Overall Survival (mOS) in this study of 17.1 months was observed, reflecting a 20% reduction in death as compared to placebo plus chemotherapy in the study (HR:

0.80, 95% CI:

0.59 - 1.08).

The Phase III study was considered to have demonstrated a tolerable safety profile and a low discontinuation rate for adverse events.

After announcing positive qualitative results for the HARMONi-2 trial, also referred to as AK112-303, a randomized, single-region (China) Phase III study sponsored by Akeso, on May 30, 2024, the Company announced, on September 8, 2024, quantitative data from the primary analysis of the Phase III HARMONi-2 trial featuring ivonescimab that was presented as part of the Presidential Symposium at the International Association for the Study of Lung Cancer’s (IASLC) 2024 World Conference on Lung Cancer (WCLC 2024).

The HARMONi-2 presentation evaluated monotherapy ivonescimab compared to monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-2 is a single region, multi-center, double-blinded Phase III study conducted in China sponsored by Akeso, with data generated and analyzed by Akeso.

In the HARMONi-2 primary analysis, ivonescimab monotherapy demonstrated a statistically significant improvement in the trial’s primary endpoint, PFS by Independent Radiologic Review Committee (IRRC), when compared to monotherapy pembrolizumab, achieving a hazard ratio of 0.51 (95% CI:

A clinically meaningful benefit was demonstrated across clinical subgroups, including patients with tumors with high PD-L1 expression.

Overall survival data was not yet mature at the time of the data cutoff and will be evaluated in the future.

Ivonescimab demonstrated an acceptable and manageable safety profile, which was consistent with previous studies.

There were three patients (1.5%) who discontinued ivonescimab due to treatment-related adverse events ("TRAEs") compared to six patients (3.0%) who discontinued pembrolizumab due to TRAEs.

There was one patient in the ivonescimab arm and two patients in the pembrolizumab arm who died as a result of TRAEs in this Phase III study.

Additional Phase II Data Sets

In addition to the HARMONi-2 data announced at WCLC 2024, Akeso also announced Phase II trial results from AK112-205, for patients with Stage II or III resectable NSCLC.

Further, the Company announced data for ivonescimab was presented as a part of the 2024 European Society for Medical Oncology Annual Meeting (ESMO 2024) featuring updated Phase II ivonescimab data in advanced triple-negative breast cancer (TNBC), recurrent / metastatic head and neck squamous cell carcinoma (HNSCC), and metastatic microsatellite-stable (MSS) colorectal cancer (CRC).

At ASCO 2024, Akeso presented ivonescimab Phase II data in biliary-tract cancer (BTC).

Earlier, at the 2024 European Lung Cancer Conference (ELCC 2024), Akeso announced updated data from AK112-201 (Cohort 1), a Phase II study for patients with first-line advanced NSCLC.

Each trial from which the data was generated was a multi-center Phase II study conducted in China sponsored by Akeso, with data generated and analyzed by Akeso.

Over 4,000 patients have been treated with ivonescimab in clinical studies globally, and over 60,000 patients when considering those treated in a commercial setting in China as noted by Akeso.

Product Pipeline

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We completed enrollment of patients in North America and Europe in October 2024.

The two primary endpoints for this study are progression-free survival ("PFS") and overall survival ("OS"), and the study compares ivonescimab plus platinum-based doublet chemotherapy versus placebo plus platinum-based doublet chemotherapy in patients with advanced or metastatic EGFR-mutated NSCLC whose tumors have progressed following treatment with a third generation EGFR-TKI.

We expect to disclose top-line results from HARMONi in mid-2025, depending upon maturation of the data per the protocol.

Food and Drug Administration ("FDA") has granted Fast Track designation for the proposed use of ivonescimab in combination with platinum-based chemotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR mutation, who have experienced disease progression following EGFR-TKI therapy.

HARMONi-3 study (NCT05899608) is a Phase III, multi-regional, potentially registration-enabling clinical trial for which we initiated activating sites in North America and China during the fourth quarter of 2023 and later in Europe in 2024.

The two primary endpoints for this study are PFS and OS, and the study compares ivonescimab plus platinum-based doublet chemotherapy versus pembrolizumab plus platinum-based doublet chemotherapy in first-line patients with metastatic squamous NSCLC and, based on changes made to the protocol in the fourth quarter of 2024, non-squamous NSCLC.

Enrollment is ongoing in all regions for patients with squamous tumors;

the protocol amendment is effective and enrollment has begun in United States in the fourth quarter of 2024 for patients with non-squamous tumors.

The Company plans to enroll an estimated 1,080 patients.

Based on the results of HARMONi-2, the Company has begun to activate clinical trial sites in the United States for HARMONi-7.

HARMONi-7 is a multi-regional Phase III clinical trial that will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic squamous and non-squamous NSCLC whose tumors have high PD-L1 expression.

The two primary endpoints for this study are PFS and OS, and the study compares ivonescimab plus platinum-based doublet chemotherapy versus placebo plus platinum-based doublet chemotherapy in patients with advanced or metastatic EGFR-mutated NSCLC whose tumors have progressed following treatment with a third generation EGFR-TKI.

In May 2025, we announced topline results from our multiregional, double-blinded, placebo-controlled, Phase III study HARMONi.

At the prespecified primary data analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement in PFS, the magnitude of which we believe to be clinically meaningful, with a hazard ratio of 0.52 (95% CI:

p<0.00001) compared to placebo in combination with chemotherapy;

median PFS was 6.8 months for those patients receiving ivonescimab plus chemotherapy compared to 4.4 months for those receiving chemotherapy.

PFS was assessed by BICR.

We believe the PFS hazard ratio that was observed in both Asian and Western sub-populations to be clinically meaningful.

The primary analysis demonstrated the consistency of the magnitude of the PFS benefit between patients randomized in Asia and Western territories, as well as the consistency in a single-region study (HARMONi-A) with this multiregional study.

0.46 – 0.71).

With the longer-term follow-up analysis, consistency of the magnitude of PFS benefit was demonstrated between patients randomized in Asia and Western patients when measured by hazard ratio.

This longer-term follow-up analysis of PFS was performed at the time of the primary OS analysis.

Ivonescimab in combination with chemotherapy showed a positive trend in OS in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI:

Currently, there are no FDA-approved regimens that have demonstrated a statistically significant overall survival benefit in this patient setting.

Both Asian and North American patients demonstrated a positive trend in overall survival.

The results of the primary analysis in this multiregional study were consistent with that of the single-region randomized Phase III HARMONi-A study, which demonstrated a statistically significant OS benefit hazard ratio of 0.74 in the primary OS analysis in a similar patient population.

nominal p=0.0332).

Median OS for this analysis remained the same in both arms as was observed in the primary analysis.

Median OS in Western patients receiving ivonescimab was 17.0 months compared to 14.0 months for those receiving placebo (HR=0.84);

median OS in North American patients, specifically, had not yet been reached in the ivonescimab arm compared to 14.0 months

in the placebo arm (HR=0.70).

Consistent benefit was observed across pre-defined subgroups.

The dual primary endpoints were allocated separate alpha levels and tested individually.

The alpha was recycled from the PFS to the OS analysis upon the successful achievement of the PFS endpoint.

The safety profile of ivonescimab in combination with chemotherapy was acceptable and manageable in the context of the observed clinical benefit with comparable rates of discontinuation and death between both arms.

There were 16 patients (7.3%) who discontinued ivonescimab due to treatment-related adverse events (“TRAEs”) compared to 11 patients (5.0%) who discontinued placebo due to TRAEs.

There were four patients (1.8%) in the ivonescimab plus chemotherapy arm and five patients (2.3%) in the chemotherapy alone arm who died as a result of TRAEs.

In the ivonescimab plus chemotherapy arm, 50.0% of patients experienced Grade 3 or higher TRAEs compared to 42.2% in the chemotherapy arm.

Of note, 0.9% of patients in the ivonescimab plus chemotherapy arm experienced Grade 3 or higher treatment-related hemorrhagic (bleeding) events.

Based on the results of the HARMONi clinical trial, Summit submitted a BLA in the fourth quarter of 2025 in order to seek approval for ivonescimab plus chemotherapy in this setting.

Summit announced in January 2026 that the FDA accepted for filing the BLA, seeking approval for ivonescimab in combination with chemotherapy for this proposed indication.

HARMONi-3 study (NCT05899608) is a Phase III, multi-regional, potentially registration-enabling clinical trial for which we initiated sites in North America, China and Europe.

Enrollment is ongoing in all regions for patients with squamous and non-squamous tumors.

In October 2025, the Company announced a protocol amendment to separate the statistical analysis of the primary endpoints by histology.

Therefore, there will be separate analyses conducted to evaluate ivonescimab plus chemotherapy compared to pembrolizumab plus chemotherapy in patients with squamous NSCLC and in patients with non-squamous NSCLC.

In order to sufficiently power for both primary endpoints (PFS and OS) in both cohorts of this study, Summit plans to enroll approximately 600 patients with squamous NSCLC and 1,000 patients with non-squamous NSCLC.

As a result of having two separate intention-to-treat analyses within the HARMONi-3 study, the analyses for squamous tumors and non-squamous tumors may be conducted at separate times, as each analysis will be conducted upon the prespecified numbers of events being reached in the separate cohorts.

Screening for patient enrollment has been completed for the planned patient count for the squamous cohort of HARMONi-3 in the first quarter of 2026.

For the squamous cohort, we amended the study’s statistical analysis plan and expect to conduct an interim analysis for PFS in the second quarter of 2026.

We anticipate that OS will be immature at the time of the interim PFS analysis.

The Company expects to reach the prespecified number of events for the final PFS analysis for this cohort, if required, in the second half of 2026.

An interim analysis for OS may be conducted at a similar time.

Enrollment in the non-squamous cohort of HARMONi-3 is expected to complete in the second half of 2026.

The Company expects to perform the final PFS analysis for this cohort in the first half of 2027.

The Company will determine if an interim PFS analysis will be conducted for the study in the second half of 2026.

Interim analyses for OS are planned to be conducted, based upon reaching prespecified numbers of events.

Based on the results of HARMONi-2, the Company is enrolling in the HARMONi-7 study (NCT06767514).

HARMONi-7 is a multi-regional, potentially registration-enabling Phase III clinical trial that will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic squamous and non-squamous NSCLC whose tumors have high PD-L1 expression.

The sample size for this study is currently planned to have an estimated 780 patients with two primary endpoints, PFS and OS.

In the fourth quarter of 2025, the Company activated trial sites and began enrolling patients in HARMONi-GI3, a Phase III, multi-regional, clinical trial evaluating ivonescimab plus chemotherapy compared to bevacizumab plus chemotherapy as first line therapy in patients with unresectable metastatic CRC.

The primary endpoint for this study is PFS and Summit plans to enroll approximately 600 patients.

Non-Sponsored Phase III Clinical Studies (Summit’s License Territories)

In the first quarter of 2026, the Company announced that GORTEC, a cooperative group dedicated to Head and Neck Oncology, will begin to activate clinical trial sites in the Phase III clinical study, ILLUMINE (NCT07264075), which will evaluate ivonescimab monotherapy and ivonescimab in combination with ligufalimab, Akeso’s proprietary anti-CD47 monoclonal antibody, against monotherapy pembrolizumab in a three-arm study.

The study is intended to be conducted in multiple countries in Europe and in China;

Summit will consider the expansion of this study into the United States.

The primary endpoint for the study is OS.

The study, currently planned to enroll 780 patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma (HNSCC), is expected to begin enrollment in the second quarter of 2026.

Data supporting this study was previously presented at ESMO 2024, whereby ivonescimab in combination with ligufalimab demonstrated an objective response rate of 60% in 20 patients with a median PFS of 7.1 months after a median follow-up time of 4.1 months;

OS was not mature at the time of this analysis.

At the time of data cut-off for this presentation, no patients receiving ivonescimab plus ligufalimab permanently discontinued drug treatment due to treatment-related adverse events.

Potential Future Clinical Development and Additional Current Activities

Summit is conducting its current clinical trials and plans to design and conduct additional clinical trial activities for ivonescimab within its Licensed Territory to support and submit relevant regulatory filings.

We intend to explore further clinical development of ivonescimab in solid tumor settings outside of metastatic non-small cell lung cancer, our current area of focus in its Phase III clinical trials.

We intend to explore further clinical development of ivonescimab in solid tumor settings outside of metastatic NSCLC and metastatic CRC, our current areas of focus in our Phase III clinical trials.

In the fourth quarter of 2023, we began collaborating with multiple institutions globally and opened our investigator- sponsored trials program across several disease areas.

We continued to expand this program in 2024 in order to discover additional opportunities for ivonescimab, including in several tumors outside of our current development plan.

We plan to review the data generated from these clinical trials as a part of our consideration for advancing our clinical development pipeline for ivonescimab in the Licensed Territory.

We continued to expand this program in 2024 and 2025 in order to discover additional opportunities for ivonescimab, including in several tumors outside of our current development plan.

We plan to review the data generated from these clinical trials as well as Akeso-sponsored clinical trials as a part of our consideration for advancing our clinical development pipeline for ivonescimab in the Licensed Territory.

Additional Ivonescimab Development:

Akeso-Sponsored Trials

Akeso is currently developing ivonescimab in NSCLC and other solid tumor settings.

Ivonescimab was approved by the National Medical Products Administration (“NMPA”) in May 2024 in China in combination with chemotherapy for patients with EGFR-mutated NSCLC whose tumors have progressed following an EGFR-TKI based on the results of the HARMONi-A clinical trial.

Subsequently, ivonescimab was approved by the NMPA in April 2025 as monotherapy based on the results of the HARMONi-2 study in first-line, PD-L1 positive NSCLC.

Also in October 2025, Akeso announced the positive data for the HARMONi-6 study in first-line squamous NSCLC for ivonescimab in combination with chemotherapy.

Further details related to these three trials, in addition to other Phase II clinical data, are described further below.

Akeso is currently conducting Phase III clinical trials in combination with chemotherapy in first-line biliary tract cancer (“HARMONi-GI1”), in first-line advanced PD-L1 low or negative triple-negative breast cancer (“TNBC”) (“HARMONi-BC1”), in first-line advanced microsatellite stable CRC (“HARMONi-GI6”) and in NSCLC for patients whose tumors have progressed following PD-(L)1 inhibitor based therapy (“HARMONi-8A”), as well as in combination with ligufalimab, a proprietary Akeso-owned investigational CD-47 monoclonal antibody, in first-line recurrent / metastatic PD-L1 positive head-and-neck cancer (“HARMONi-HN1”) and in combination with ligufalimab plus chemotherapy in first-line advanced pancreatic cancer (“HARMONi-GI2”).

In addition, Akeso is conducting a Phase 3 study with ivonescimab after consolidation chemotherapy and radiotherapy in the limited stage small cell lung cancer (“SCLC”) setting (HARMONi-9).

Based on data published by Akeso at the American Society of Clinical Oncology (“ASCO 2024”) and in a publication in the Journal of the American Medical Association (JAMA) in the HARMONi-A study, in a single-region (China), randomized, double-blinded Phase III study in patients with NSCLC who have progressed following an EGFR-TKI, ivonescimab achieved its primary endpoint of PFS when combined with doublet chemotherapy (pemetrexed and carboplatin).

Patients experienced a 54% reduction in disease progression or death as compared to placebo plus doublet-chemotherapy (HR:

0.46, 95% CI:

In a pre-specified subgroup analysis of patients who received a previous third-generation TKI, a hazard ratio of 0.48 was observed.

At the primary OS analysis of HARMONi-A, ivonescimab achieved a hazard ratio of 0.74 (95% CI:

0.95, p=0.019), demonstrating a statistically significant and clinically meaningful OS benefit, which was presented in November 2025 at the 2025 Annual Meeting for the Society for Immunotherapy for Cancer (SITC 2025).

Ivonescimab demonstrated an acceptable and manageable safety profile, which was consistent with previous studies.

There were nine patients (5.6%) who discontinued ivonescimab plus chemotherapy due to TRAEs compared to four patients (2.5%) who discontinued chemotherapy plus placebo due to TRAEs.

No TRAEs resulted in the death of a patient in either arm in this Phase III study.

Full results were published in JAMA (Fang et al.

After announcing positive qualitative results on May 30, 2024 for the HARMONi-2 trial, also referred to as AK112-303, a randomized, single-region (China) Phase III study sponsored by Akeso, quantitative data was presented on September 8, 2024 from the primary analysis as part of the Presidential Symposium at the International Association for the Study of Lung Cancer’s (“IASLC”) 2024 World Conference on Lung Cancer (“WCLC 2024”).

The HARMONi-2 presentation evaluated monotherapy ivonescimab compared to monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-2 is a single region, multi-center, double-blinded Phase III study conducted in China sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso.

In the HARMONi-2 primary analysis, ivonescimab monotherapy demonstrated a statistically significant improvement in the trial’s primary endpoint, PFS by Independent Radiologic Review Committee (“IRRC”), when compared to monotherapy pembrolizumab, achieving a hazard ratio of 0.51 (95% CI:

A clinically meaningful benefit was demonstrated across clinical subgroups, including patients with tumors with high PD-L1 expression.

OS data was not yet mature at the time of the data cutoff of the primary PFS analysis.

Ivonescimab demonstrated an acceptable and manageable safety profile, which was consistent with previous studies.

There were three patients (1.5%) who discontinued ivonescimab due to TRAEs compared to six patients (3.0%) who discontinued pembrolizumab due to TRAEs.

There was one patient in the ivonescimab arm and two patients in the pembrolizumab arm who died as a result of TRAEs in this Phase III study.

Full results were published in Lancet (Xiong et al.

On April 25, 2025, Akeso announced that ivonescimab was approved in China by the NMPA for a second indication based on the results of the HARMONi-2 trial.

As a part of the review of the supplemental marketing application submitted by Akeso seeking a label expansion of ivonescimab in China, the NMPA requested that Akeso perform an interim analysis of OS.

Akeso announced that the results of this interim OS analysis included a clinically meaningful hazard ratio of 0.777.

The analysis was conducted at 39% data maturity, with a nominal alpha level of 0.0001 that had not reached statistical significance.

After announcing positive qualitative results for the HARMONi-6 trial, on April 23, 2025, detailed clinical trial results of the study were presented as part of the Presidential Symposium at the European Society for Medical Oncology’s 2025 Congress (“ESMO 2025”).

The HARMONi-6 study evaluated ivonescimab in combination with platinum-based chemotherapy compared to tislelizumab (a PD-1 inhibitor) in combination with platinum-based chemotherapy in patients with previously untreated advanced NSCLC irrespective of PD-L1 expression.

HARMONi-6, also referred to as AK112-306, is a single region, multi-center, double-blinded Phase III study conducted in China sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso.

In the HARMONi-6 planned PFS interim analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint, PFS, by IRRC, when compared to tislelizumab in combination with chemotherapy, achieving a hazard ratio of 0.60 (95% CI:

A clinically meaningful benefit was demonstrated across clinical subgroups, including those with either PD-L1 negative or positive expression, as well as high-risk patients.

OS data was not yet mature at the time of the data cutoff and is planned to be evaluated in the future.

Ivonescimab demonstrated an acceptable and manageable safety profile in the HARMONi-6 study, which was consistent with previous Phase III studies conducted studying ivonescimab.

Nine patients (3.4%) discontinued ivonescimab plus chemotherapy due to TRAEs compared to 11 patients (4.2%) receiving tislelizumab plus chemotherapy due to TRAEs.

There were eight patients in the ivonescimab plus chemotherapy arm and 10 patients in the tislelizumab plus chemotherapy arm who died as a result of TRAEs in this Phase III study.

Results were published in Lancet (Chen et al.

Additional Phase II Data Sets

In addition to the HARMONi-2 data announced at WCLC 2024, Akeso also announced Phase II trial results from AK112-205, for patients with Stage II or III resectable NSCLC.

Further, the Company announced data for ivonescimab was presented as a part of the 2024 European Society for Medical Oncology Annual Congress (“ESMO 2024”) featuring updated Phase II ivonescimab data in advanced TNBC, for which subsequent updates to the data have been presented thereafter, recurrent /

metastatic head and neck squamous cell carcinoma, and metastatic microsatellite-stable CRC.

At ASCO 2024, Akeso presented ivonescimab Phase II data in biliary-tract cancer.

Earlier, at the 2024 European Lung Cancer Conference, Akeso announced updated data from AK112-201 (Cohort 1), a Phase II study for patients with first-line advanced NSCLC.

Each trial from which the data was generated was a multi-center Phase II study conducted in China sponsored by Akeso, with data generated and analyzed by Akeso.

The markets for oncology pharmaceuticals, in which we compete, are characterized by significant scientific innovation, regulatory oversight and intense competition.

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Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient, or are less expensive than any products that we may develop.

Our competitors also may obtain marketing approvals for their products more rapidly than we obtain approval for ours.

This may have the effect of making branded products less attractive from a cost perspective to buyers.

Our competitors also may obtain marketing approvals for their products more rapidly than we obtain approval for ours giving them significant first movers advantage.

Our commercial opportunity could also be reduced or eliminated if the results of our clinical trials, both safety and efficacy, combined with other factors, do not lead to significant adoption of our product.

Competition for ivonescimab

Ivonescimab is currently being investigated in global Phase III clinical trials in Summit’s Licensed Territory in two metastatic NSCLC indications:

(b) ivonescimab combined with chemotherapy in first-line metastatic squamous NSCLC patients (“HARMONi-3”)

In addition, the Company has begun to activate clinical trial sites in the United States for a Phase III clinical study in the following proposed indication:

The Company is developing ivonescimab in NSCLC and CRC, specifically conducting Phase III clinical trials in the following proposed indications:

(a) ivonescimab combined with chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR-TKI (“HARMONi”);

(c) ivonescimab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression (“HARMONi-7”);

(d) ivonescimab combined with chemotherapy in patients with first-line unresectable metastatic CRC (“HARMONi-GI3”).

Ivonescimab is also being investigated in multiple Phase II and Phase III clinical trials in China.

We plan to review the data generated from these clinical trials as a part of our consideration for advancing our clinical development pipeline for ivonescimab in the Licensed Territory.

We plan to review the data generated from these clinical trials as well as other data generated in studies with ivonescimab as a part of our consideration for advancing our clinical development pipeline for ivonescimab in the Licensed Territory.

There are no known PD-1-based bispecific antibodies currently approved by the FDA, the European Medicines Agency (“EMA”), or Japan’s Pharmaceuticals and Medical Devices Agency (“PMDA”).

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However, there are several PD-(L)1/VEGF(R2) bispecific antibodies in development around the world, including multiple that are currently in development or with planned development globally.

These include, but are not limited to BNT327, which is owned by BioNTech SE, which has begun conducting Phase III clinical studies globally, and LM-299, which was licensed globally by Merck & Co., Inc.

in November 2024.

Our current clinical development plan in the Licensed Territory is focused on NSCLC.

These include, but are not limited to pumitamig (BNT327), which is owned by BioNTech SE and being developed in a collaboration with Bristol Myers Squibb Co.

since June 2025, which has begun conducting Phase III clinical studies globally, PF’4404 (SSGJ-707 / PF-08634404), which was licensed globally, ex-China by Pfizer Inc.

in July 2025, LM-299, which was licensed globally by Merck & Co., Inc.

in November 2024, and RC148, which was licensed outside of Greater China by AbbVie Inc.

in January 2026.

Our current clinical development plan in the Licensed Territory has focused primarily on NSCLC.

Several pharmaceutical and biotechnology companies have established themselves in the market for the treatment of NSCLC, and several additional companies are developing products for the treatment of NSCLC.

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There are anti-angiogenic therapies which are approved for the treatment of certain lung cancers, including bevacizumab in front-line non-squamous NSCLC, as well as ramucirumab for patients who have progressed after platinum-based chemotherapy.

The proposed indications for ivonescimab in the HARMONi-3 and HARMONi-7 clinical trial settings in first-line NSCLC may face competition from clinical candidates

such as novel immunotherapy targets including various clinical candidates targeting T-cell immunoreceptors with Ig and ITIM domains (TIGIT) and lymphocyte activation gene 3 (LAG-3) each of which have various developers for different candidates as either monoclonal antibodies or multispecific antibodies, a bispecific antibody, volrustomig (AstraZeneca), and antibody drug conjugates (ADCs) with novel targets such as datopotamab deruxetecan (AstraZeneca and Daiichi Sankyo), sacituzumab tirumotecan (Merck), and sigvotatug vedotin (Pfizer), each having announced, are currently enrolling in, or having completed enrollment in Phase III clinical trials.

For those patients EGFR mutations, there are several targeted therapies that have also been approved in the front-line setting, including, but not limited to, osimertinib (AstraZeneca) with or without chemotherapy and amivantamab and lazertinib (both from Johnson & Johnson).

The proposed indication for ivonescimab in the HARMONi clinical trial setting, post third-generation EGFR-TKIs such as osimertinib or lazertinib, may face competition from amivantamab plus chemotherapy, as well as clinical candidates such as as datopotamab deruxetecan (AstraZeneca and Daiichi Sankyo) and patritumab deruxtecan (Merck and Daiichi Sankyo).

The proposed indications for ivonescimab in the HARMONi-3 and HARMONi-7 clinical trial settings in first-line NSCLC may face competition from clinical candidates such as novel immunotherapy targets including various clinical candidates targeting T-cell immunoreceptors with Ig and ITIM domains (TIGIT) and lymphocyte activation gene 3 (LAG-3) each of which have various developers for different candidates as either monoclonal antibodies or multispecific antibodies, a bispecific antibody, volrustomig (AstraZeneca), rilvegostomig (AstraZeneca) and antibody drug conjugates (ADCs) with novel targets such as datopotamab deruxetecan (AstraZeneca and Daiichi Sankyo), sacituzumab tirumotecan (Merck), and sigvotatug vedotin (Pfizer), each having announced, are currently enrolling in, or having completed enrollment in Phase III clinical trials.

Phase III clinical trials with pumitamig and PF’4404 are being conducted or intentions to conduct have been announced by their respective sponsors in first-line NSCLC in combination with chemotherapy, similar to the setting in which HARMONi-3 is currently being conducted.

For those patients with advanced NSCLC with EGFR mutations, there are several targeted therapies that have also been approved in the front-line setting, including, but not limited to, osimertinib (AstraZeneca) with or without chemotherapy and amivantamab and lazertinib (both from Johnson & Johnson).

The proposed indication for ivonescimab in the HARMONi clinical trial setting, post third-generation EGFR-TKIs such as osimertinib or lazertinib, may face competition from amivantamab plus chemotherapy and datopotamab deruxetecan (AstraZeneca and Daiichi Sankyo), which are fully approved post TKI and have an accelerated approval post TKI and post chemotherapy, respectively.

In addition, investigational agents such as sacituzumab tirumotecan (Merck), izalontamab brengitecan (BMS), telisotuzumab adizutecan (AbbVie) and savolitinib (AstraZeneca) are currently being investigated in the post-TKI setting in those patients with advanced EGFR mutation positive NSCLC.

Beyond NSCLC, we are currently conducting the Phase III study for patients with first line metastatic unresectable CRC, HARMONi-GI3.

For those patients with metastatic unresectable CRC whose tumors are not designated as mismatch repair deficient or have a specific treatable driver mutation (e.g., BRAF) in the first-line setting, there are limited treatment options beyond the currently approved regimens of bevacizumab plus chemotherapy, as well as cetuximab plus chemotherapy for a subset of these patients.

Intentions to conduct Phase III clinical trials with pumitamig and PF’4404 have been announced by their respective sponsors in first-line metastatic unresectable CRC, similar to the setting in which HARMONi-GI3 is currently being conducted.

In addition, novel agents such as amivantamab plus chemotherapy are currently being investigated in a subset of this setting.

Should ivonescimab ultimately receive marketing authorization in certain jurisdictions within the Licensed Territory, the marketing authorization holder for some of the approved agents may lose exclusive rights to these agents, increasing competition from biosimilar agents or generic compounds.

As we intend to explore further clinical development of ivonescimab in solid tumor settings outside of metastatic non-small cell lung cancer, our current area of focus in our Phase III clinical trials, we will encounter significant competition in the development of ivonescimab in each of these potential settings.

As we intend to explore further clinical development of ivonescimab in solid tumor settings outside of metastatic NSCLC and metastatic CRC, our current area of focus in our Phase III clinical trials, we will encounter significant competition in the development of ivonescimab in each of these potential settings.

Manufacturing

We do not own or operate, and currently have no plans to establish, manufacturing facilities for the production of clinical or commercial quantities of ivonescimab.

We do not own or operate, and currently have no plans to own manufacturing facilities for the production of clinical or commercial quantities of ivonescimab.

We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates and any products that we may develop.

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Until such time that we are able to establish second source suppliers or are able to manufacture the drug substance independently, Akeso shall be solely responsible for the manufacture of the drug substance for use in the Licensed Territory.

We continue to make progress in transferring relevant know-how to third parties to establish additional supply sources.

We continue to make progress in transferring relevant

know-how to third parties to establish additional supply sources.

We are using a different third-party supplier for clinical packaging, labeling and distribution of the clinical drug product.

Intellectual Property

We have obtained and maintain proprietary protection for our antibiotic product candidates, technology and know-how.

We have obtained and maintain proprietary protection for our product candidates, technology and know-how.

We strive to protect the proprietary technology by, among other methods, seeking and maintaining patents, where available, that are intended to cover our product candidates, compositions and formulations, their methods of use and processes for their manufacture and any other inventions that are commercially important to the development of our business.

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We continue to develop, identify, and strive to protect other technologies that are commercially relevant to our ivonescimab position.

Patent Number Country/Region* Patent Type Not Due to Expire Before**

12195527 United States Compositions of Matter August 30, 2039

3882275 Europe Compositions of Matter & Methods of Manufacture/Use August 30, 2039

7374995 Japan Compositions of Matter & Methods of Manufacture/Use August 30, 2039

7589314 Japan Methods of Use August 30, 2039

*Additional granted patents and/or pending patent applications in the U.S., Europe, Japan, and other countries/regions, not due to expire before 2039 to 2042, may be available.

**Dates do not account for any available patent term adjustment/extensions/supplemental protection certificates and assume that all maintenance/annuity fees are timely paid.

Our current ivonescimab patents cover regions including the United States, Europe and Japan and include compositions of matter and methods of preparation / use.

Our current ivonescimab patents expire from 2039 – 2040.

The protection afforded by any particular patent depends upon many factors, including the type of patent, scope of coverage encompassed by the granted claims, availability of extensions of patent term, availability of legal remedies in the particular territory in which the patent is granted, and success of any challenges to the patent, if asserted.

Changes in either patent laws or in the interpretation of patent laws in the United States and other countries could diminish our ability to protect our inventions and to enforce our intellectual property rights.

Accordingly, we cannot predict with certainty the enforceability of any granted patent claims or of any claims that may be granted from our patent applications.

Trade Secrets .

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Trade secrets and know-how can be difficult to protect;

We seek to protect our proprietary technology and processes, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors, manufacturers, and commercial partners.

however, we take reasonable steps to protect our proprietary technology and processes, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors, manufacturers, and commercial partners.

These agreements are designed to protect our proprietary information and, in the case of the invention assignment agreements, to grant us ownership of technologies that are developed through a relationship with a third party.

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In connection with the development of our product pipeline, we will seek protection for marks we currently use and future marks when appropriate.

We may not be able to obtain, maintain or protect the intellectual property rights necessary to conduct our business, and we may be subject to claims, whether or not meritorious, that we infringe or otherwise violate the intellectual property rights of third parties.

For more information, please see the section on “Risk Factors – Risks Related to Intellectual Property”.

Government Regulation

As a biopharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for serious diseases, we are subject to extensive and ongoing regulation by government authorities, including regulation by the United States Food and Drug Administration ( “ FDA ” ) under the Federal Food, Drug, and Cosmetic Act (“FDCA”) and its implementing regulations, as well as by other regulatory bodies in the United States, Europe and other countries in which we operate.

Government authorities in the United States, at the federal, state and local level, and in other countries and jurisdictions, including the European Union, extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, packaging, storage, record keeping, labeling, pricing, reimbursement, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of pharmaceutical products.

As a biopharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for serious diseases, we are subject to extensive and ongoing regulation by government authorities, including regulation by the FDA under the Federal Food, Drug, and Cosmetic Act (“FDCA”) and its implementing regulations, as well as by other regulatory bodies in the United States, Europe and other countries in which we operate.

The processes for obtaining regulatory approvals in the United States and in foreign countries and jurisdictions, along with compliance with applicable statutes and regulations and other regulatory authorities, require the expenditure of substantial time and financial resources.

Review and Approval of Drugs in the United States

Review and Approval of Drugs and Biological Products in the United States

In the United States, the FDA regulates drugs under the FDCA and implementing regulations.

An entity that takes responsibility for the initiation and management of a clinical development program for such products, and for their regulatory approval, is typically referred to as a “ sponsor ” or “ applicant.

An entity that takes responsibility for the initiation and management of a clinical development program for such products, and for their regulatory approval, is

typically referred to as a “sponsor” or “applicant.” Biological products used for the prevention, treatment or cure of a disease or condition of a human being are subject to regulation under the FDCA, except that the section of the FDCA that governs the approval of new drug applications (“NDAs”) does not apply to the approval of biological products.

Biological products are approved for marketing under provisions of the Public Health Service Act (the “PHSA”), via a BLA.

However, the application process and requirements for approval of BLAs are very similar to those for NDAs, and biologics are associated with similar approval risks and costs as drugs.

The failure of a sponsor to comply with the FDCA and applicable U.S.

requirements at any time during the product development process, approval process or after approval may subject an applicant or sponsor to a variety of administrative or judicial sanctions, including imposition of a clinical hold or other delays in the conduct of a study, refusal by the FDA to approve pending applications, withdrawal of an approval, issuance of warning letters and other types of letters, product recalls, product seizures, total or partial suspension of production, importation or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by the FDA and the Department of Justice (“DOJ”), or other federal and state governmental entities.

An applicant seeking approval to market and distribute a new drug product in the United States must typically undertake the following:

• completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice (“GLP”) regulations;

An applicant seeking approval to market and distribute a new drug or biological product in the United States must typically undertake the following:

• completion of nonclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice (“GLP”) regulations;

• submission to the FDA of an Investigational New Drug (“IND”) Application, which must take effect before human clinical trials may begin;

• approval by an independent institutional review board, or IRB, approving each clinical study at each research site before a clinical trial may be initiated at the site;

• approval by an independent institutional review board (“IRB”) of each clinical study at each research site before a clinical trial may be initiated at the site;

• performance of adequate and well-controlled human clinical trials in accordance with current good clinical practice (“GCP”) standards, to establish the safety and efficacy of the proposed drug product for each indication;

• preparation and submission to the FDA of a new drug application (“NDA”) or Biologic Licensing Application (“BLA”);

• preparation and submission to the FDA of an NDA or BLA;

• a determination by the FDA within 60 days of its receipt of an NDA or BLA to file the submission for review;

• review of the product candidate by an FDA advisory committee, where appropriate or if applicable;

• satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with current Good Manufacturing Practices (“cGMP”), requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;

• satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data submitted in support of the NDA/BLA;

• satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with current Good Manufacturing Practices (“cGMP”), requirements and to ensure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;

• satisfactory completion of FDA audits of clinical trial sites to ensure compliance with GCPs and the integrity of the clinical data submitted in support of the NDA/BLA;

• payment of user fees and securing FDA approval of the NDA/BLA for the marketing of the drug product;

• compliance with any post-approval requirements, including Risk Evaluation and Mitigation Strategies (“REMS”), where applicable, and any post-approval studies required by the FDA.

Preclinical Studies

Nonclinical Studies

Before an applicant begins testing a compound with potential therapeutic value in humans, the product candidate must undergo rigorous preclinical testing.

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The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations and the United States Department of Agriculture's Animal Welfare Act, if applicable.

The results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and plans for clinical trials, among other things, are submitted to the FDA as part of an IND.

Some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue after the IND is submitted.

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Stability studies must be conducted to demonstrate that the candidate product does not undergo unacceptable deterioration over its shelf-life.

The IND and Institutional Review Board ( “ IRB ” ) Processes

An IND is an exemption from the FDCA that allows an unapproved drug to be shipped in interstate commerce for use in a clinical investigational clinical trial and serves as a request for FDA authorization to administer an investigational drug to humans.

The IND and IRB Processes

An IND is an exemption from the FDCA that allows an unapproved drug to be shipped in interstate commerce for use in a clinical investigation and serves as a request for FDA authorization to administer an investigational drug to humans.

Such authorization must be secured prior to interstate shipment and administration of any new drug that is not the subject of an approved NDA/BLA.

In support of a request for an IND, applicants must submit a protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND.

In support of a request for an IND, a sponsor must submit a protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND.

In addition, the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and plans for clinical trials, among other things, are submitted to the FDA as part of an IND.

The FDA requires a 30-day waiting period after the filing of each new IND before clinical trials may begin.

The FDA requires a 30-day waiting period after the submission of each new IND before clinical trials may begin.

This waiting period is designed to allow the FDA to review the IND to determine whether human research subjects will be exposed to unreasonable health risks.

At any time during this 30-day

period, the FDA may raise concerns or questions about the conduct of the trials as outlined in the IND and impose a clinical hold.

At any time during this 30-day period, the FDA may raise concerns or questions about the conduct of the trials as outlined in the IND and impose a clinical hold.

In this case, the IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can begin.

Following commencement of a clinical trial under an IND, the FDA may also place a clinical hold or partial clinical hold on that trial.

Clinical holds are imposed by the FDA when there is concern for patient safety and may be a result of new data, findings, or developments in clinical, nonclinical, and/or chemistry, manufacturing, and controls, or CMC.

A clinical hold is an order issued by the FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation, and FDA must provide a basis for its imposition within 30 days after imposition of a clinical hold.

A partial clinical hold is a delay or suspension of fewer than all of the clinical investigations subject to the IND.

Following issuance of a clinical hold or partial clinical hold, an investigation may only resume after the FDA has notified the sponsor that the investigation may proceed.

A partial clinical hold is a delay or suspension of fewer than all of the clinical investigations, or certain parts of a clinical investigation, subject to the IND.

Following issuance of a clinical hold or partial clinical hold, an investigation, or the parts of the investigation subject to the partial clinical hold, may only resume after the FDA has notified the sponsor that the investigation may proceed.

The FDA will base that determination on information provided by the sponsor correcting the deficiencies previously cited or otherwise satisfying the FDA that the investigation can proceed.

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When the foreign clinical study is not conducted under an IND, the sponsor must ensure that the study complies with certain regulatory requirements of the FDA in order to use the study as support for an IND or application for marketing approval.

Specifically, on April 28, 2008, the FDA amended its regulations governing the acceptance of foreign clinical studies not conducted under an IND as support for an IND or an NDA or BLA.

The final rule provides that such studies must be conducted in accordance with GCP, including review, approval, and continuing review by an independent ethics committee, or IEC, and freely given informed consent from subjects.

The GCP requirements in the final rule encompass both ethical and data integrity standards for clinical studies.

The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality and integrity of the resulting data.

Specifically, such studies must be conducted in accordance with GCP, including review, approval, and continuing review by an independent ethics committee, or IEC, and freely given informed consent from subjects.

The GCP requirements encompass both ethical and data integrity standards for clinical studies.

The FDA’s requirements are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality and integrity of the resulting data.

They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies.

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

Additionally, some trials are overseen by an independent group of qualified experts with relevant expertise that organized by the trial sponsor, but should be independent of the sponsor, and is known as a data safety monitoring board or data safety monitoring committee (“DSMB ” ).

A DSMB recommends to the sponsor whether to continue, modify, or stop a trial or trials based on its periodic review of accumulating data from one or more clinical trials.

Suspension or termination of a clinical trial or a clinical development program during any phase of clinical trials can occur if it is determined that the participants or patients are being exposed to an unacceptable health risk.

Additionally, some trials are overseen by an independent group of qualified experts with relevant expertise known as a data safety monitoring board or data safety monitoring committee (“DSMB ” ).

A DSMB is organized by the trial sponsor but should be independent of the sponsor.

The DSMB recommends to the sponsor whether to continue, modify, or stop a trial or trials based on its periodic review of accumulating data from one or more clinical trials.

Suspension or termination of a clinical trial or a clinical development program during any phase of clinical trials can occur if it is determined by the FDA, an IRB/EC, the sponsor, or the clinical investigator that the participants or patients are being exposed to an unacceptable health risk.

Other reasons for suspension or termination may be made by us based on evolving business objectives and/or competitive climate.

Information about clinical trials must be submitted within specific timeframes to the National Library of Medicine (“NLM”), for public dissemination on its ClinicalTrials.gov website.

The failure to submit clinical trial information to clinicaltrials.gov, as required, is a prohibited act under the FDCA with violations subject to potential civil monetary penalties.

Similar requirements for posting clinical trial information are present in the European Union (EudraCT) website:

https://eudract.ema.europa.eu/ and other countries, as well.

Information about certain clinical trials must be submitted within specific timeframes for public dissemination on its ClinicalTrials.gov website.

The failure to submit such clinical trial information to clinicaltrials.gov, as required, is a prohibited act under the FDCA with violations subject to potential civil monetary penalties.

Expanded Access to an Investigational Drug for Treatment Use

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The rules and regulations related to expanded access are intended to improve access to investigational drugs for patients who may benefit from investigational therapies.

FDA regulations allow access to investigational drugs under an IND by the company upon request by the treating physician for treatment purposes on a case-by-case basis for:

individual patients (single-patient IND applications for treatment in emergency settings and non-emergency

FDA regulations allow access to investigational drugs under a protocol submitted to an IND for:

individual patients (single-patient IND applications for treatment in emergency settings and non-emergency settings);

intermediate-size patient populations;

and larger populations for use of the drug under a treatment protocol or Treatment IND Application.

and larger populations for use of the drug.

When considering an IND application for expanded access to an investigational product with the purpose of treating a patient or a group of patients, the sponsor and treating physicians or investigators will determine suitability when all of the following criteria apply:

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and the expanded use of the investigational drug for the requested treatment will not interfere with initiation, conduct, or completion of clinical investigations that could support marketing approval of the product or otherwise compromise the potential development of the product.

On December 13, 2016, the 21st Century Cures Act established (and the 2017 Food and Drug Administration Reauthorization Act later amended) a requirement that sponsors of one or more investigational drugs for the treatment of a serious disease(s) or condition(s) make publicly available their policy for evaluating and responding to requests for expanded access for individual patients.

Although these requirements were rolled out over time, they have now come into full effect.

This provision requires drug and biologic companies to make publicly available their policies for expanded access for individual patient access to products intended for serious diseases.

Sponsors are required to make such policies publicly available upon the earlier of initiation of a Phase II or Phase III study;

Sponsors of one or more investigational drugs for the treatment of a serious disease(s) or condition(s) must make publicly available their policy for evaluating and responding to requests for expanded access for individual patients.

Sponsors are required to make expanded access policy publicly available upon the earlier of the first initiation of a Phase II or Phase III study with respect to such investigational drug;

or 15 days after the drug or biologic receives designation as a breakthrough therapy, fast track product, or regenerative medicine advanced therapy.

Sponsors are not required to provide access to investigational products via expanded access, but the manufacturer must develop an internal policy and respond to patient requests according to that policy.

In addition, on May 30, 2018, the Right to Try Act was signed into law.

The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase I clinical trial and that are undergoing investigation for FDA approval.

In addition, the Right to Try Act, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval.

Under certain circumstances, eligible patients can seek access to an investigational drug product without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program.

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Progress reports of the clinical trials must be submitted at least annually to the FDA, and more frequently in some circumstances, such as if serious adverse events occur.

In addition, IND safety reports must be submitted to the FDA for any of

the following:

In addition, IND safety reports must be submitted to the FDA for any of the following:

serious and unexpected suspected adverse reactions;

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and any clinically important increase in the case of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

Phase I, Phase II and Phase III clinical trials may not be completed successfully within any specified period, or at all.

Furthermore, the FDA or other regulatory authority 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, a reviewing IRB/EC can suspend or terminate approval of a clinical trial at a clinical trial site if the clinical trial is not being conducted in accordance with the IRB’s/EC’s requirements or if the drug has been associated with unexpected serious harm to patients.

The FDA or other regulatory authority will typically inspect one or more clinical trial sites prior to approval of an NDA or BLA to assure compliance with GCP and assess the integrity of the clinical data submitted in support of the NDA or BLA.

Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, or at all.

Under the Pediatric Research Equity Act (“PREA”) of 2003, an application or supplement to an NDA or BLA for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration must contain a pediatric assessment unless the applicant has obtained a waiver or deferral.

The pediatric assessment includes data to assess the safety and effectiveness of the drug product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective or reasons why dosing in pediatric patients is not recommended.

The FDA also may require holders of approved NDAs and BLAs for marketed drugs and biological products to conduct pediatric studies under certain circumstances.

With enactment of the Food and Drug Administration Safety and Innovation Act (“FDASIA”), in 2012, sponsors of drug product applications subject to PREA must also submit pediatric study plans prior to the assessment data during the development program.

Sponsors of drug product applications subject to PREA must also submit pediatric study plans during the development program.

Those plans must contain an outline of the proposed pediatric study or studies the applicant plans to conduct, any deferral or waiver requests and other information required or applicable by regulation.

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The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements.

Additional requirements and procedures relating to deferral requests and requests for extension of deferrals are contained in FDASIA.

The FDA Reauthorization Act of 2017 established new requirements to govern certain molecularly targeted cancer indications.

Any company that submits an NDA/BLA three years after the date of enactment of that statute must submit pediatric assessments with the NDA/BLA if the drug is intended for the treatment of an adult cancer and is directed at a molecular target that the FDA determines to be substantially relevant to the growth or progression of a pediatric cancer.

Any company that submits an NDA/BLA for certain cancer indications must submit pediatric assessments with the NDA/BLA if the drug is intended for the treatment of an adult cancer and is directed at a molecular target that the FDA determines to be substantially relevant to the growth or progression of a pediatric cancer.

The investigation must be designed to yield clinically meaningful pediatric study data regarding the dosing, safety and preliminary efficacy to inform pediatric labeling for the product.

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Under federal law, the submission of most NDAs and BLAs is subject, under the Prescription Drug User Fee Reauthorization Act of 2022 (“PDUFA VII”), to an application user fee, which for federal fiscal year 2026 is $4,682,000 for an application requiring clinical data.

The sponsor of the approved NDA/BLA is also subject to an annual program fee, which for the fiscal year 2025 is $403,889.

Certain exceptions and waivers are available for some of these fees, such as an exception from the application fee for products with orphan designation and a waiver for certain small businesses.

The applicant for an approved NDA/BLA is also subject to an annual program fee, which for the fiscal year 2026 is $442,213.

Certain exceptions and waivers are available for some of these fees, such as an exception from the application fee for products with orphan designation and a waiver for the first application for certain small businesses.

Following submission of an application, the FDA conducts a filing review of an NDA or BLA within 60 calendar days of its receipt and strives to inform the sponsor by the 74th day after the FDA’s receipt of the submission whether the application is sufficiently complete to permit substantive review.

The FDA may request additional information rather than accept an NDA or BLA for filing.

The FDA may refuse to file any NDA or BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information rather than file an NDA or BLA.

In this event, the application must be resubmitted with the additional information.

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

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

The resubmitted application is also subject to review before the FDA files it.

Once the submission is filed, the FDA begins an in-depth substantive review.

The FDA has agreed to certain performance goals in the review process of NDAs and BLAs.

Under the agency's PDUFA VII commitments, 90% of applications seeking approval of new molecular entities (“NMEs”), are meant to be reviewed within ten months from the date on which FDA accepts the NDA for filing, and 90% of applications for NMEs that have been designated for “priority review” are meant to be reviewed within six months of the acceptance date.

Under the agency's PDUFA VII commitments, 90% of applications seeking approval of new molecular entities (“NMEs”) are meant to be reviewed within ten months from the date on which FDA files the NDA or BLA, and 90% of applications for NMEs that have been designated for “priority review” are meant to be reviewed within six months of the filing date.

The review process may be extended by the FDA for three additional months to consider new information or clarification provided by the applicant to address an outstanding deficiency identified by the FDA following the original submission.

The FDA does not always meet its PDUFA goal dates for standard and priority applications.

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

These pre-approval inspections cover all or selected facilities associated with an NDA/BLA submission, including drug component manufacturing (such as API), finished drug product manufacturing, and control testing laboratories.

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 or BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP.

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 ensure consistent production of the product within required specifications.

Additionally, before approving an NDA or BLA, the FDA will typically inspect one or more clinical sites to ensure compliance with GCP.

In addition, as a condition of approval, the FDA may require an applicant to develop a REMS.

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To determine whether a REMS is needed, the FDA will consider the size of the population likely to use the product, seriousness of the disease, expected benefit of the product, expected duration of treatment, seriousness of known or potential adverse events, and whether the product is a new molecular entity.

REMS can include medication guides, physician communication plans for healthcare professionals, and elements to assure safe use (“ETASU”).

REMS can include medication guides, physician communication plans for healthcare professionals, and elements to ensure safe use (“ETASU”).

ETASU may include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries.

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The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in the treatment of a serious or life-threatening disease or condition.

These programs are referred to as fast-track designation, breakthrough therapy designation, priority review designation and regenerative medicine advanced therapy designation.

Specifically, the FDA may designate a product for fast-track review if it is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition.

These programs are referred to as fast-track designation, breakthrough therapy designation and priority review designation.

Specifically, the FDA may grant fast track designation to a product if it is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition.

For fast track products, sponsors may have greater interactions with the FDA, and the FDA may initiate review of sections of a fast track product’s application before the NDA or BLA is complete.

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The sponsor must also provide, and the FDA must approve, a schedule for the submission of the remaining information and the sponsor must pay applicable user fees.

However, the FDA’s time period goal for reviewing a fast-track application does not begin until the last section of the NDA or BLA is submitted.

However, the FDA’s goal for reviewing a fast track application does not begin until the last section of the NDA or BLA is submitted.

In addition, the fast track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging from the clinical development program.

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Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation.

A priority designation is intended to direct overall attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on a marketing application from ten months to six months.

A priority review designation is intended to direct overall attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on a marketing application from ten months to six months following the FDA’s filing of the application.

Accelerated Approval Pathway

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All promotional materials for product candidates approved under accelerated regulations are subject to prior review by the FDA.

The Food and Drug Omnibus Reform Act of 2022 (“FDORA”) modified certain statutory provisions governing accelerated approval of drug and biologic products.

The Food and Drug Omnibus Reform Act of 2022 modified certain statutory provisions governing accelerated approval of drug and biologic products.

Specifically, the new legislation authorized the FDA to:

require a sponsor to have its confirmatory clinical trial well underway before accelerated approval is awarded, require a sponsor of a product granted accelerated approval to submit progress reports on its post-approval studies to FDA every six months;

and use expedited procedures to withdraw accelerated approval of an NDA or BLA if a confirmatory trial fails to verify the product’s clinical benefit.

In March 2023, the FDA issued draft guidance outlining its current thinking and approach to accelerated approval.

and use expedited procedures to withdraw accelerated approval of an NDA or BLA if a confirmatory trial fails to verify the product’s clinical benefit or the sponsor fails to conduct the required confirmatory trial with due diligence.

In March 2023, the FDA issued draft guidance outlining its current thinking and approach to accelerated approval for oncology therapeutics.

Noting that the accelerated approval pathway is commonly used for approval of oncology drugs due to the serious and life-threatening nature of cancer, FDA’s guidance outlined considerations for designing, conducting, and analyzing data for trials intended to support accelerated approvals of oncology products.

FDA recommended a randomized controlled trial as the preferred approach to assessing the safety and efficacy as it provides a more robust efficacy and safety assessment and allows for direct comparisons to an available therapy.

This is a departure from the previously common use of single-arm trials to support accelerated approval of oncology products.

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The FDA’s Decision on an NDA or BLA

On the basis of the FDA’s evaluation of the NDA or BLA and accompanying information, including the results of the inspection of the manufacturing facilities, the FDA may issue an approval letter or a complete response letter.

On the basis of the FDA’s evaluation of the NDA or BLA and accompanying information, including the results of the inspection of the manufacturing facilities, the FDA will issue an approval letter or a complete response letter.

An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications.

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If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA or BLA, the FDA will issue an approval letter.

The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included.

The FDA has committed to

reviewing such resubmissions in two or six months depending on the type of information included.

Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

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

After approval, many 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.

Post-Approval Requirements

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After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval.

There also are continuing, annual program fee requirements for any marketed product, as well as new application fees for supplemental applications that include clinical data.

There also are continuing, annual program fee requirements for any marketed product.

The FDA may impose a number of post-approval requirements as a condition of approval of an NDA.

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Accordingly, manufacturers must continue to expend time, money and effort in the area of production, quality control and pharmacovigilance to maintain cGMP compliance.

Once an approval is granted, the FDA may withdraw marketing approval for marketing of a drug product if compliance with regulatory requirements and standards is not maintained or if unanticipated adverse events or other safety concerns occur after the product reaches the market.

Once an approval is granted, the FDA may withdraw marketing approval for a drug product if compliance with regulatory requirements and standards is not maintained or if unanticipated adverse events or other safety concerns occur after the product reaches the market.

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

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Promotional claims about a drug’s safety or effectiveness are prohibited before the drug is approved.

After approval, a drug product generally may not be promoted for uses that are not approved by the FDA, as reflected in the product’s approved prescribing information.

After approval, a drug product may not be promoted for uses that are not approved by the FDA, as reflected in the product’s approved prescribing information.

In the United States, health care professionals are generally permitted to prescribe drugs for such uses not described in the drug’s labeling, known as off-label uses, because the FDA does not regulate the practice of medicine.

However, FDA regulations impose rigorous restrictions on manufacturers’ communications, prohibiting manufacturers and their representatives from promoting a drug product for off-label uses or uses that are otherwise inconsistent with the product’s labeling.

with the product’s labeling.

It may be permissible, under very specific, narrow conditions, for a manufacturer to engage in non-promotional, non-misleading communication regarding uses of a product that are inconsistent with a product’s labeling, such as distributing certain scientific information or publications such as medical journal articles.

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The PDMA, its implementing regulations and state laws limit the distribution of prescription pharmaceutical product samples, and the DSCSA imposes requirements to ensure accountability in distribution and to identify and remove counterfeit and other illegitimate products from the market.

Marketing Exclusivity and Biosimilars

The Biologics Price Competition and Innovation Act of 2009 created an abbreviated approval pathway for biological products shown to be biosimilar to an FDA-licensed reference biological product.

Biosimilarity, which requires that the biological product be highly similar to the reference product notwithstanding minor differences in clinically inactive components and that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency, can be shown through analytical studies, toxicity studies, and a clinical trial or trials.

A biosimilar may be approved as interchangeable with its reference biological product.

Interchangeability requires that a biological product both be biosimilar to the reference product and that the product can be expected to produce the same clinical results as the reference product in any given patient and, for products administered multiple times to an individual, that the product and the reference product may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biological product without such alternation or switch.

Under most state laws, interchangeable products may be used in place of the reference biological product.

A reference biological product is granted 12 years of data exclusivity from the time of first licensure of the product during which the FDA will not approve a biosimilar referencing the reference biological product, and the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product.

“First licensure” typically means the initial date the particular product at issue was licensed in the United States.

Date of first licensure does not include the date of licensure of (and a new period of exclusivity is not available for) a biological product if the licensure is for a supplement for the biological product or for a subsequent application by the same sponsor or manufacturer of the biological product (or licensor, predecessor in interest, or other related entity) for a change that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or strength, or for a modification to the structure of the biological product that does not result in a change in safety, purity or potency.

Pediatric Exclusivity

Pediatric exclusivity is one type of non-patent marketing exclusivity available to drug manufacturers in the United States who have met criteria qualifying their products for pediatric exclusivity and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity for each of the manufacturers products with the same active moiety, including the non-patent and orphan exclusivity.

This six-month exclusivity may be granted if an NDA/BLA sponsor submits pediatric data or fairly respond to a written request from the FDA for such data.

Pediatric exclusivity is an extension of existing non-patent marketing exclusivity available to biological product manufacturers in the United States who have met criteria qualifying their products for pediatric exclusivity and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity for each of the manufacturers products with the same active moiety, including the non-patent and orphan exclusivity.

This six-month exclusivity may be granted if an NDA/BLA sponsor submits pediatric data or fairly responds to a written request from the FDA for such data.

The data do not need to show the product to be effective in the pediatric population studied;

rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the studies were completed using appropriate formulations and within the requested time frame, and the studies were conducted in accordance with commonly accepted scientific principles, the additional protection may be granted.

Upon any exclusivity determination by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection cover the product are extended by six months.

This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot approve another generic or biosimilar application.

additional protection may be granted.

Upon any exclusivity determination by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity cover the product are extended by six months.

Patent Term Restoration and Extension

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patent that covers a drug, biological product or medical device approved pursuant to a premarket approval may also be eligible for patent term extension when FDA approval is granted, provided that certain statutory and regulatory requirements are met.

The length of the patent term extension is related to the length of time the drug is under regulatory review while the patent is in force.

The length of the patent term extension is related to the length of time the drug is under development and regulatory review while the patent is in force, reduced by any time during which the applicant failed to exercise due diligence.

The Hatch-Waxman Act permits a patent term extension of up to five years beyond the expiration date set for the patent.

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A manufacturer may request an orphan drug designation for either a previously unapproved product or a new use of an FDA-approved product.

Orphan drug designation must be requested before approval of an NDA or BLA.

Orphan drug designation must be requested before submission of an NDA or BLA.

Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process, though companies developing orphan products may be eligible for certain financial incentives such as tax credits for qualified clinical testing or waiver of certain application fees.

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This is a seven-year period of marketing exclusivity during which FDA may not approve any other applications to market the same active ingredient or active moiety for the same indication, except in limited circumstances.

Such limited circumstances may include a subsequent product’s showing of clinical superiority over the product with orphan drug exclusivity.

Such limited circumstances may include a subsequent product’s showing of clinical superiority over the product with orphan drug exclusivity or drug shortage.

Competitors, however, may receive approval of different active ingredients or active moieties for the same indication or obtain approval for the same therapeutic agent or active moiety for a different indication.

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Clinical Trial Approval

The Clinical Trials Regulation 536/2014, the Directive 2005/28/EC on Good Clinical Practice (“GCP”), and the related national implementing provisions of the individual E.U.

Member States govern the system for the approval of clinical trials in the E.U.

Under this system, an applicant must obtain prior approval from a national competent authority in one of the E.U.

Member States in which the clinical trial is to be conducted.

Furthermore, the applicant may only start a clinical trial at a specific study site after the competent ethics committee has issued a favorable opinion.

The clinical trial application must be accompanied by, among other documents, an investigational medicinal product dossier (the Common Technical Document) with supporting information prescribed by legal frameworks regarding medicinal products (as set out in Directive 2001/20/EC and Regulation 726/2004), the GCP Directive 2005/28/EC, and, where relevant, the implementing national provisions of the individual E.U.

Member States and further detailed in applicable guidance documents.

On January 31, 2022, the Clinical Trials Regulation, (E.U.) No 536/2014 (the “Clinical Trials Regulation”) fully replaced the previous Clinical Trials Directive 2001/20/EC (and any national legislation implementing the Directive).

The Clinical Trials Regulation is directly applicable in all the E.U.

The Clinical Trials (EU) No Regulation 536/2014 (“CTR”), Commission Implementing Regulation (EU) 2017/556 on the detailed arrangements for the GCP, Commission Delegated Regulation (EU) 2017/1569 and Commission Directive (EU) 2017/1572 on Good Manufacturing Practice (“GMP”) and Commission Guidelines such as Volume 10 of “The rules governing medicinal products in the European Union” govern the system for the approval of clinical trials in the E.U.

Under this system,

an applicant planning to conduct a clinical trial on an investigational medicinal product in the EU or European Economic Area (EEA”) must apply for authorization of this trial through the EU central single entry point:

the Clinical Trials Information System (“CTIS”).

The applicant submits its application dossier via CTIS, consisting of (among other documents) the cover letter, the EU application form, the study protocol and the Investigational Medicinal Product Dossier.

The applicant shall submit this dossier to the intended Member States concerned through CTIS and shall propose one of the Member States concerned as the Reporting Member State (“RMS”).

The RMS validates the application and reviews whether the application dossier is complete.

After this, the RMS will draw up an assessment report (Part I of the approval process).

For Part II of the approval process, all Concerned Member States shall assess, for their own territory, the application dossier of the applicant.

Each Concerned Member State shall notify the applicant through the EU CTIS portal as to whether the clinical trial is authorized, whether it is authorized subject to conditions, or whether authorization is refused.

On January 31, 2022, the CTR became applicable.

From this date, a three-year transition period started, to ensure that ongoing clinical trials could align with the rules as laid down in the CTR.

From 31 January 2025 onwards, all clinical trials in the EU/EEA must be conducted in accordance with the CTR.

This means that the Clinical Trials Directive 2001/20/EC (and any national legislation implementing the Directive) is now fully replaced by the CTR.

The CTR is directly applicable in all the E.U.

Member States.

The Clinical Trials Regulation simplifies and streamlines the approval of clinical trials in the E.U.

The CTR simplifies and streamlines the approval of clinical trials in the E.U.

The main characteristics of the Regulation include:

a streamlined application procedure via a single entry point, the “E.U.

Portal and Database;” a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors;

and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts.

Part I is assessed by the appointed reporting Member State, whose assessment report is submitted for review by the sponsor and all other competent authorities of all E.U.

Member States in which an application for authorization of a clinical trial has been

submitted (“Concerned Member States”).

a streamlined application procedure via a single entry point, the CTIS;

a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors;

and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts as described above.

Part I is assessed by the appointed RMS, whose assessment report is submitted for review by the sponsor and all other competent authorities of all E.U.

Member States in which an application for authorization of a clinical trial has been submitted.

Part II is assessed separately by each Concerned Member State.

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We anticipate that the centralized procedure will be mandatory for the product candidates we are developing.

Under the centralized procedure, the Committee for Medicinal Products for Human Use (“CHMP”) is also responsible for several post-authorization and maintenance activities, such as the assessment of modifications or extensions to an existing marketing authorization.

Under the centralized procedure in the E.U., the maximum timeframe for the evaluation of an MAA is 210 days, excluding clock stops, when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP.

Under the centralized procedure, the Committee for Medicinal Products for Human Use (“CHMP”) – EMA’s committee responsible for human medicines – is also responsible for several post-authorization and maintenance activities, such as the assessment of modifications or extensions to an existing marketing authorization.

Under the centralized procedure in the E.U., the maximum timeframe for the evaluation of an MAA is 210 days after submission of a valid application, excluding clock stops, when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP.

Overall, the assessment of a new medicine usually lasts around a year.

Accelerated evaluation might be granted by the CHMP in exceptional cases when a medicinal product is of major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation.

If the CHMP accepts such request, the time limit of 210 days will be reduced to 150 days, but the CHMP can revert to the standard time limit for the centralized procedure if it determines that it is no longer appropriate to conduct an accelerated assessment.

If the CHMP accepts such request, the time limit of 210 days will be

reduced to 150 days, but the CHMP can revert to the standard time limit for the centralized procedure if it determines that it is no longer appropriate to conduct an accelerated assessment.

At the end of this period, the CHMP provides a scientific opinion on whether or not a marketing authorization should be granted in relation to a medicinal product.

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The European Parliament also has a related “droit de regard.” The European Parliament’s role is to ensure that the European Commission has not exceeded its powers in deciding to grant or refuse to grant a marketing authorization.

The European Commission may grant a so-called “marketing authorization under exceptional circumstances.” Such authorization is intended for products for which the applicant can demonstrate that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use, because the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence, or in the present state of scientific knowledge, comprehensive information cannot be provided, or it would be contrary to generally accepted principles of medical ethics to collect such information.

The European Commission may grant a so-called “marketing authorization under exceptional circumstances” on the basis of article 14(8) of Regulation (EC) No 726/2004.

Such authorization is intended for products for which the applicant can demonstrate that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use, for objective, verifiable reasons, for instance because the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence, or in the present state of scientific knowledge, comprehensive information cannot be provided, or it would be contrary to generally accepted principles of medical ethics to collect such information.

The Rapporteur, Co-Rapporteur and the other CHMP members will assess the justification/data submitted for exceptional circumstances as part of the overall assessment of the benefit/risk of the application.

Consequently, marketing authorization under exceptional circumstances may be granted subject to certain specific obligations, which may include the following:

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Thus, a marketing authorization under exceptional circumstances is granted for an initial five years, after which the authorization will become valid indefinitely, unless the EMA decides that safety grounds merit one additional five-year renewal.

The European Commission may also grant a so-called “conditional marketing authorization” prior to the applicant obtaining the comprehensive clinical data required for an application for a full marketing authorization.

The European Commission may also grant a so-called “conditional marketing authorization” on the basis of article 14a of Regulation (EC) No 726/2004, prior to the applicant obtaining the comprehensive clinical data required for an application for a full marketing authorization, in order to meet unmet medical needs of patients and in the interest of public health.

Such conditional marketing authorizations may be granted for product candidates (including medicines designated as orphan medicinal products) if:

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The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional marketing authorization.

medicines framework expressly permits the E.U.

Member States to adopt national legislation prohibiting or restricting the sale, supply or use of any medicinal product containing, consisting of or derived from a specific type of human or animal cell, such as embryonic stem cells.

Applicants for a potential conditional marketing authorization are strongly encouraged to engage in early dialogue with EMA and other stakeholders (e.g.

health technology assessment bodies) and discuss their development plan.

EMA also encourages applicants to request accelerated assessment for products deemed suitable for a conditional marketing authorization.

medicines framework preserves the competence of the E.U.

Member States to adopt national legislation prohibiting or restricting the sale, supply or use of any medicinal product containing, consisting of or derived from a specific type of human or

animal cell, such as embryonic stem cells.

While the products we have in development do not make use of embryonic stem cells, it is possible that the national laws in certain E.U.

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Member State.

For certain applications, such as applications for products designated as orphan medicinal products or products falling under the compulsory scope of the centralized procedure, the mutual recognition procedure and the decentralized procedure cannot be used.

Regulatory Data Protection in the E.U.

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During an additional two-year period of market exclusivity, a generic MAA can be submitted and authorized, and the innovator’s data may be referenced, but no generic medicinal product can be placed on the E.U.

market until the expiration of the market

market until the expiration of the market exclusivity.

The overall ten-year period will be extended to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

Even if a compound is considered to be a new chemical entity so that the innovator gains the prescribed period of data exclusivity, another company nevertheless could also market another version of the product if such company obtained marketing authorization based on an MAA with a complete independent data package of pharmaceutical tests, preclinical tests and clinical trials.

In April 2023, the European Commission published a proposal to reform the current pharmaceutical framework, including revision of the regulatory data protection system.

In the latest version of the proposal, published on 11 December 2025, the regulatory data protection will consist of 8 years of data exclusivity, same as under the current legal framework, and one additional year of market exclusivity.

This means a total of 8+1 years of protection, instead of the current 8+2 years.

Under the reformed legislation, there will be a possibility to obtain one additional year of exclusivity (8+1+1) under certain circumstances and another year (8+1+1 or 8+1+1+1) for a new indication of significant clinical benefit, with a capped overall regulatory protection of 11 years.

The final text of the reform proposal is expected to be endorsed and published in the first half of 2026 and, after a transition period, the new legislation is expected to start to apply from mid-2028.

Orphan Drug Designation and Exclusivity

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and that without incentives it is unlikely that the marketing of the drug in the EU would generate sufficient return to justify the necessary investment.

For either of these conditions, the sponsor must demonstrate that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the E.U.

For either of these conditions, the sponsor must demonstrate that there

exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the E.U.

or, if such method exists, the medicinal product will be of significant benefit to those affected by that condition.

Once authorized, orphan medicinal products are entitled to 10 years of market exclusivity in all E.U.

Member States and in addition a range of other benefits during the development and regulatory review process including scientific assistance for study protocols, authorization through the centralized marketing authorization procedure covering all member countries and a reduction or elimination of registration and marketing authorization fees.

Member States and in addition a range of other benefits during the development and regulatory review process including scientific assistance for study protocols, authorization through the centralized marketing authorization procedure covering all Member States and a reduction or elimination of registration and marketing authorization fees.

However, marketing authorization may be granted to a similar medicinal product with the same orphan indication during the 10-year period with the consent of the marketing authorization holder for the original orphan medicinal product, or if the manufacturer of the original orphan medicinal product is unable to supply the medicine in sufficient quantities.

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or (b) is sufficiently profitable not to justify maintenance of market exclusivity.

The proposal to reform the current pharmaceutical framework as mentioned above also intends to revise the orphan drug designation and exclusivity regime.

In the latest version of the proposal, orphan market exclusivity will be reduced from the current 10 years to 9 years.

Extension by another 2 years will be possible for so-called “breakthrough orphan medicinal products”.

Although the final text has not yet been published, previous drafts also included the concept of “global orphan marketing authorization”, which would no longer grant additional separate orphan market exclusivity for second or further orphan therapeutic indications.

Also, previous drafts allowed generics, biosimilars or other second applicants to apply for marketing authorization two years before expiry of orphan market exclusivity thus effectively reducing the innovator’s market exclusivity compared to the current legal framework.

Again, final text of the reform proposal is expected to be endorsed and published in Q1 or Q2 of 2026 and, after a transition period, the new legislation is expected to start to apply from mid-2028.

Periods of Authorization and Renewals

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• The manufacturing of authorized medicinal products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the applicable E.U.

laws, regulations and guidance, including Directive 2001/83/EC, Directive 2017/1572/EC, Regulation (EC) No 726/2004 and the European Commission Guidelines for Good Manufacturing Practice.

laws, regulations and guidance, including Directive 2001/83/EC, Directive 2017/1572/EC, Regulation (EC) No 726/2004 and the European Commission Guidelines for GMP.

These requirements include compliance with E.U.

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Direct-to- consumer advertising of prescription medicines is prohibited across the E.U.

Pricing Decisions for Approved Products

In the E.U., pricing and reimbursement schemes vary widely from country to country.

Some countries provide that products may be marketed only after a reimbursement price has been agreed.

Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies or so- called health technology assessments in order to obtain reimbursement or pricing approval.

For example, the E.U.

provides options for its Member States to restrict the range of products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

Member States may approve a specific price for a product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.

Other Member States allow companies to fix their own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.

Recently, many countries in the E.U.

have increased the amount of discounts (or rebates) required on pharmaceuticals and these efforts could continue as countries attempt to manage health care expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the E.U.

The downward pressure on health care costs in general, particularly prescription products, has become intense.

As a result, increasingly high barriers are being erected to the entry of new products.

Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained.

Reference pricing used by various Member States, and parallel trade, i.e., arbitrage between low-priced and high-priced Member States, can further reduce prices.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any products, if approved in those countries.

Patent Term Extension

In order to compensate the patentee for delays in obtaining a marketing authorization for a patented product, a supplementary protection certificate (“SPC”) may be granted extending the exclusivity period for that specific product by up to five years.

In order to compensate the patentee for delays in obtaining a marketing authorization for a patented product, a supplementary protection certificate (“SPC”) in E.U.

Member State or Patent Term Extension (“PTE”) in U.S.

may be granted extending the exclusivity period for that specific product by up to five years.

PTE applications must be filed with the USPTO within 60 days of regulatory approval.

Applications for SPCs must be made to the relevant patent office in each E.U.

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Member States.

Brexit and the Regulatory Framework in the United Kingdom (“UK”)

Regulatory Framework in the United Kingdom (“UK”)

The United Kingdom’s withdrawal from the E.U.

took place on January 31, 2020.

The EU and the UK reached an agreement on their new partnership in the Trade and Cooperation Agreement, or the Agreement, and which entered into force on May 1, 2021.

The Agreement focuses primarily on free trade by ensuring no tariffs or quotas on trade in goods, including healthcare products such as medicinal products.

Thereafter, the E.U.

and the UK will form two separate markets governed by two distinct regulatory and legal regimes.

As such, the Agreement seeks to minimize barriers to trade in goods while accepting that border checks will become inevitable as a consequence that the UK is no longer part of the single E.U.

As of January 1, 2021, the Medicines and Healthcare products Regulatory Agency (the “MHRA”), became responsible for supervising medicines in Great Britain under domestic law.

The MHRA also supervises medicines in Northern Ireland, albeit largely on the basis of E.U.

rules as a result of the Northern Ireland Protocol.

On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”.

This new framework fundamentally changes the existing system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK.

In particular, the MHRA is responsible for approving all medicinal products destined for the UK market (i.e., Great Britian and Northern Ireland), and the EMA will no longer have any role in approving medicinal products destined for Northern Ireland.

A single UK-wide marketing authorization will be granted by the MHRA for all medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.

took place on January 31, 2020 (“Brexit”).

The EU and the UK have two separate markets governed by two distinct regulatory and legal regimes, although the UK’s GMP and GCP frameworks remain largely based on the EU frameworks.

On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the “Northern Ireland Protocol” which was put in place shortly after Brexit with a new set of arrangements, known as the “Windsor Framework”.

The Windsor Framework was approved by the EU-UK Joint Committee on March 24, 2023, and each of the UK government and the E.U.

have enacted legislative measures to bring it into law.

On June 9, 2023, the MHRA announced that the medicines aspects of the Windsor Framework will apply from January 1, 2025.

The Windsor Framework fundamentally changed the post-Brexit system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK.

From January 1, 2025, the UK’s Medicines and Healthcare products Regulatory Agency (the “MHRA”) became responsible for approving all medicinal products destined for the UK market (i.e., Great Britian and Northern Ireland) via a single UK-wide marketing authorization, enabling products to be sold in a single pack and under a single authorization throughout the UK.

New medicinal products assessed by the MHRA are designated as one of two categories.

“Category 1” medicinal products are those which fall within the mandatory or optional scope of the EU’s centralized procedure and are assessed on the basis of UK legislation.

“Category 2” medicinal products are those which do not fall within Category 1 and are authorized in accordance with UK and EU law.

Under the MHRA’s international recognition framework (in place since January 1, 2024), the MHRA will have regard to decisions on the approval of MAs made by the EMA and certain other regulators when determining an application for a new UK MA.

The Human Medicines Regulations 2012 (SI 2012/1916) (as amended) (“HMR”) is the primary legal instrument for the regulation of medicines in the UK.

The HMR has incorporated into the domestic law the body of EU law instruments governing medicinal products that pre-existed prior to the UK’s withdrawal from the EU.

EU laws which have been transposed into UK law through secondary legislation continue to be applicable as “retained EU law.” However, new legislation such as the (EU) Clinical Trials Regulation will not be applicable in GB.

Since a significant proportion of the regulatory framework for pharmaceutical products in the UK covering the quality, safety and efficacy of pharmaceutical products, clinical trials, MAs, commercial sales, and distribution of pharmaceutical products is derived from EU Directives and Regulations, Brexit may have a material impact upon the regulatory regime with respect to the development, manufacture, importation, approval, and commercialization of our product candidates in the UK.

For example, the UK is no longer covered by the centralized procedures for obtaining EU-wide MAs from the EMA, and a separate MA will be required to market our product candidates in the UK.

A new international recognition framework has been in place since January 1, 2024, whereby the MHRA will have regard to decisions on the approval of MAs made by the EMA and certain other regulators when determining an application for a new Great Britain MA.

EU laws which have been transposed into UK law through secondary legislation continue to be applicable as “retained EU law.” New EU legislation, such as the (EU) Clinical Trials Regulation, is not applicable in Great Britain but does apply in Northern Ireland as a result of the Windsor Framework.

The UK’s Medicines for Human Use (Clinical Trials) Regulations 2004 implement the requirements of the previous EU clinical trials regime under Directive 2001/20/EC, but will be modernized by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024, which were passed into law on April 10, 2025 and come into effect of April 28, 2026.

Healthcare Law and Regulation

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• the federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalties laws, which prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false, fictitious or fraudulent or knowingly making, using or causing to be made or used a false record or statement to avoid, decrease or conceal an obligation to pay money to the federal government;

execute, a scheme to defraud any healthcare benefit program or making false statements relating to health care matters;

• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, which impose obligations on certain of our customers and business partners who are covered entities and their business associates, as defined by HIPAA, that may impact the way we do business with them, including mandatory contractual terms, and requirements for safeguarding the privacy, security and transmission of individually identifiable protected health information;

• the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created additional federal criminal laws that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false statements relating to health care matters;

• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, impose obligations on covered entities and their business associates, as defined by HIPAA, including mandatory contractual terms, and requirements for safeguarding the privacy, security and transmission of individually identifiable protected health information;

• Foreign Corrupt Practices Act (“FCPA”), which prohibits companies and their intermediaries from making, or offering or promising to make improper payments to non-U.S.

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• the federal false statements statute, which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services;

• the federal transparency requirements known as the federal Physician Payments Sunshine Act, under the Patient Protection and Affordable Care Act, as amended by the Health Care Education Reconciliation Act, or the Affordable Care Act (“ACA”), which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the United States Department of Health and Human Services, information related to payments and other transfers of value made by that entity to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;

• the federal transparency requirements known as the federal Physician Payments Sunshine Act, under the Patient Protection and Affordable Care Act, as amended by the Health Care Education Reconciliation Act, or the Affordable Care Act (“ACA”), which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services (“CMS”), within the United States Department of Health and Human Services, information related to payments and other transfers of value made by that entity to physicians 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 anti-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by non-government third-party payors, including private insurers.

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Manufacturers are required by the laws of some states to make certain disclosures or certifications related to their compliance activities to state agencies or on the manufacturer’s website.

Others may impose restrictions on, or registration requirements for, a manufacturers sales representatives.

Others may impose restrictions on, or registration requirements for, a manufacturer’s sales representatives.

Some state laws require manufacturers to report information related to payments to physicians and other healthcare providers, marketing expenditures, or price information for certain drug products.

State and foreign laws also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are broader than and/or not preempted by HIPAA, thus complicating compliance efforts.

State and foreign laws also govern the privacy and security of health information in some circumstances, many of which differ from each

other in significant ways and often are broader than and/or not preempted by HIPAA, thus complicating compliance efforts.

Manufacturers are expected to expend substantial resources to implement compliance controls to prevent and detect noncompliance with these requirements.

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A decision by a third-party payor not to cover a product could reduce physician utilization once the product is approved and have a material adverse effect on sales, results of operations and financial condition.

Additionally, a payor’s

decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved.

Further, one payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage and reimbursement for the product, and the level of coverage and reimbursement can differ significantly from payor to payor.

Additionally, a payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved.

Further, one payor’s determination to provide coverage for a product does not ensure that other payors will also provide coverage and reimbursement for the product, and the level of coverage and reimbursement can differ significantly from payor to payor.

Pricing Decisions for Approved Products

In the E.U., pricing and reimbursement schemes vary widely from country to country.

Some countries provide that products may be marketed only after a reimbursement price has been agreed.

For example, the E.U.

Member States may approve a specific price for a product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.

Other Member States allow companies to fix their own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.

Recently, many countries in the E.U.

The downward pressure on health care costs in general, particularly prescription products, has become intense.

As a result, increasingly high barriers are being erected to the entry of new products.

Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained.

Reference pricing used by various Member States, and parallel trade, i.e., arbitrage between low-priced and high-priced Member States, can further reduce prices.

Pharmaceutical Price Reforms

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Most significantly, on the federal level, the Inflation Reduction Act (the “IRA”) was signed into law on August 16, 2022.

The IRA contained substantial pharmaceutical pricing updates to the Medicare program.

The extent and scope of impacts the IRA may have on our product candidates, once approved, will continue to evolve as the new administration advances implementation of the IRA’s pharmaceutical pricing provisions.

The IRA contained substantial pharmaceutical pricing updates to the Medicare programs.

The extent and scope of impacts the IRA may have will continue to evolve as the current administration advances implementation of the IRA’s pharmaceutical pricing provisions.

Several changes included in the IRA may impact pricing, disrupt current pharmaceutical supply chain operations, and alter stakeholder behavior in a manner that ultimately reshapes the industry and impacts areas beyond the Medicare program.

For example, each year, CMS will engage with selected high-spend Medicare Part D and Part B single-source drug and biologic products as part of the “Medicare Drug Price Negotiations Program,”.

These negotiations compel manufacturers of these products to negotiate substantial discounts to the Medicare program or face substantial penalties.

For example, each year, CMS will engage with selected high-spend Medicare Part D and Part B single-source drug and biologic products as part of the “Medicare Drug Price Negotiations Program.” These negotiations compel manufacturers of these products to negotiate substantial discounts to the Medicare program or face substantial penalties.

The pricing reached during these negotiations will likely have significant impacts on selected and related products, such as on pricing, prescribing, and formulary management, within Medicare and secondarily in other coverage markets.

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Additionally, on October 20, 2020, HHS and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program to import certain prescription drugs from Canada into the U.S.

That regulation was challenged in a lawsuit by the Pharmaceutical Research and Manufacturers of America, or PhRMA, but the case was dismissed by a federal district court in February 2023 after the court found that PhRMA did not have standing to sue HHS.

That regulation was challenged in a lawsuit by the Pharmaceutical Research and Manufacturers of America (“PhRMA”), but the case was dismissed by a federal district court in February 2023 after the court found that PhRMA did not have standing to sue HHS.

Nine states (Colorado, Florida, Maine, New Hampshire, New Mexico, North Dakota, Texas, Vermont and Wisconsin) have passed laws allowing for the importation of drugs from Canada.

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On January 5, 2024, the FDA approved Florida’s plan for Canadian drug importation.

Changes within the landscape of the 340B Drug Pricing Program (the “340B Program”) stemming from recent litigation, enforcement activity, and state and federal legislative interest and efforts may also have implications for revenues generated from our potential product candidates, as approved.

Established by Section 340B of the Public Health Service Act and overseen by the Health Resources and Services Administration (“HRSA”), the 340B Program requires manufacturers to sell outpatient prescription drugs to certain statutorily-defined safety net "covered entities" at significantly discounted prices.

This plan was granted extensions until May 6, 2026.

It is unclear how this program will be implemented, if at all, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada.

Recent litigation, enforcement activity, and state and federal legislative interest and efforts have resulted in changes within the landscape of the 340B Drug Pricing Program (the “340B Program”).

Established by Section 340B of the PHSA and overseen by the Health Resources and Services Administration (“HRSA”), the 340B Program requires manufacturers to sell outpatient prescription drugs to certain statutorily-defined safety net “covered entities” at significantly discounted prices.

In recent years, there has been increased third-party utilization of the 340B Program as a result of expanded interpretations of the statute by covered entities, which has had implications for manufacturers of covered outpatient drugs.

Potential statutory or regulatory updates at the federal level, in addition to 340B-related litigation, could significantly reshape the 340B Program and its resulting impact on future sales of our potential product candidates, as approved.

Notably, the landscape of contract pharmacy involvement in the dispensing of 340B drugs sold to covered entities particularly on the state-level—has continued to evolve through enforcement activity, litigation, and state-level legislation.

The changes stemming from

continued litigation and state activity, as well as the growing number of contract pharmacies, or any related federal legislative activity may continue to impact the volume of drugs purchased at 340B prices and the 340B Program’s impact on our product candidates, if approved.

The changes stemming from continued litigation and state activity, as well as the growing number of contract pharmacies, or any related federal legislative activity may continue to impact the volume of drugs purchased at 340B prices and the 340B Program’s impact on our product candidates, if approved.

In May 2025, the current administration published an executive order regarding most favored nation (“MFN”) drug pricing, which is sometimes referred to as international reference pricing.

This executive order directs the Secretary of Health and Human Services to communicate MFN price targets to pharmaceutical manufacturers, and if significant progress towards MFN pricing is not delivered, to propose a rule making plan to impose MFN pricing.

HHS is currently developing a proposed rule to establish a demonstration model under the auspices of CMS’s Center for Medicare and Medicaid Innovation that will require MFN pricing, but the proposed rule has not yet been published, so it is not yet known which drugs will be covered, how long the model will be in effect, or how pricing will be determined.

If that rule or other MFN pricing rules are finalized, they are likely to establish reference price controls on U.S.

drug prices, using prices in comparator countries as the benchmark for allowable U.S.

reimbursement.

More broadly, individual states are increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, provisions designed to encourage importation from other countries and bulk purchasing of drug products by state agencies.

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

The evolving nature of these federal and state measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing.

We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could also impact third party payor behavior and result in reduced demand for our product candidates or additional pricing pressures.

The evolving nature of these federal and state measures could reduce ultimate demand for products, once approved, or put pressure on our product pricing.

Additional state and federal healthcare reform measures may be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could also impact third party payor behavior and result in reduced demand or additional pricing pressures.

General Data Protection Regulation and other Privacy Laws

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We are committed to fostering an inclusive work environment where employees are empowered to contribute to Summit’s mission while simultaneously enhancing their professional development.

for the betterment of overall human health and making a significant difference in the quality and potential duration of life for oncology patients.

We are committed to employing the best talent regardless of the employee’s gender, age, ethnicity or sexual orientation.

Our workforce consists of world-class leaders and experienced professionals to include, scientists, researchers, regulatory experts, clinical development specialists and business administrators working together to resolve serious, unmet medical needs for the betterment of overall human health and making a significant difference in the quality and potential duration of life for oncology patients.

We are committed to employing the best talent regardless of the employee’s gender, age, ethnicity, sexual orientation, or any other characteristic protected by applicable law.

As of December 31, 2025, we had 265 total employees.

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Summit’s culture continues to be at the center of its success.

A huge part of Summit’s cultures is its core values, which are:

Summit’s core values are a huge part of Summit’s culture, and include:

Integrity – to uphold the highest standards;

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As Summit continues to grow, maintaining and emphasizing Summit’s core values will be essential in maintaining its culture.

In addition to core values, employee engagement is a priority.

Summit’s employee engagement committee hosts employee events year-round celebrating achievements, honoring holidays as well as work anniversaries.

This year in conjunction with HR, the engagement committee rolled out an award recognition program designed to recognize excellence and outstanding employee contributions to Summit’s mission.

Belief in Summit’s mission and commitment to help patients is not only a core value but continues to be at the forefront of employee engagement.

Summit utilizes employee surveys to receive employee feedback as well as to measure the level of employee engagement.

In a June 2024 survey with an 85% participation rate, 100% of employees indicated they believed in ivonescimab’s ability to help patients.

In November 2024, Summit employees participated in the Great Place to Work Survey and received the Great Place To Work® certification, with 91% of employees believing in the statement that Summit is a great place to work.

In November 2025, Summit employees participated in the Great Place to Work Survey and has been able to maintain its Great Place To Work® certification for a second year in a row, with 81% of employees believing in the statement that Summit is a great place to work.

We believe these results continue to show employees to be engaged, enthusiastic and strongly aligned with the Company’s mission.

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We are committed to the health and safety of all of our employees.

We accomplish this through the goals of compliance with applicable workplace safety laws and regulations, continuous risk assessment and expeditious action.

We accomplish this through goals of compliance with applicable workplace safety laws and regulations, continuous risk assessment and expeditious action.

We had no reportable health and safety issues in 2025.

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Other trademarks, service marks, and trade names appearing in this Annual Report on Form 10-K are the property of their respective owners.

Solely for convenience, some of the trademarks, service marks, and trade names referred to in this Annual Report on Form 10-K are listed without the ® and ™ symbols.

Solely for convenience, some of the

trademarks, service marks, and trade names referred to in this Annual Report on Form 10-K are listed without the ® and ™ symbols.

Available Information

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We are not including the information contained on our website as part of, or incorporating it by reference into, this Annual Report on Form 10-K.

Through our website, we make available free of charge our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and amendments to these reports in a timely manner after we provide them to the SEC.

Through our website, we make available free of charge our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, amendments to these reports in a timely manner after we provide them to the SEC, and other material information from time to time in our press releases, annual meetings of stockholders, publicly accessible conferences and investor presentations.

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