What changed in this filing

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Item 1. Business

2025-02-24 compared with 2024-02-20 · 421 added, 340 removed, 331 unchanged (70% of the section changed)

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

and its affiliates (“Akeso”) pursuant to which the Company has in-licensed ivonescimab.

Through the License Agreement, the Company obtained the rights to develop and commercialize ivonescimab in the United States, Canada, Europe, and Japan (the “Licensed Territory”).

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

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.

The Company’s operations will be 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 indications:

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").

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 squamous NSCLC patients (“HARMONi-3”)

As of the date of these financial statements, both studies are enrolling patients.

The entry into the License Agreement with Akeso represents a significant change in the Company’s strategy and its future operations will be focused on the development of ivonescimab and other future activities as the Company determines.

The Company’s portfolio includes ridinilazole, a product candidate for treating patients suffering from Clostridioides difficile infection, also known as C.

difficile infection, or CDI.

All prior development and marketing activities related to ridinilazole have been terminated.

The Company’s anti-infectives portfolio includes SMT-738, the first of a novel class of precision antibiotics for combating multidrug resistant infections, specifically carbapenem-resistant Enterobacteriaceae (“CRE”) infections.

The Company will continue to pursue partnerships for further development of SMT-738.

(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:

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.

Akeso Collaboration and License Agreement

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Akeso will retain 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 comprising 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.

In addition, the Company will potentially owe Akeso (a) milestone payments tied to achievement of regulatory approval of ivonescimab with various regulatory authorities in Licensed Territory (b) milestone payments tied to achievement of annual revenue from ivonescimab in Licensed Territory and (c ) Royalty payments equal to low-double-digit percentage of annual revenues from ivonescimab in Licensed Territory.

In connection with the License Agreement, the Company has also agreed to enter into a Supply Agreement with Akeso;

pursuant to the License Agreement, Summit agreed to purchase a certain portion of drug substance for clinical and commercial supply (the “Supply Agreement”).

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

Furthermore, 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 for which Summit paid an upfront payment of $15.0 million cash in the third quarter of 2024.

In addition, the Company may also pay Akeso (a) milestone payments tied to achievement of regulatory approval of ivonescimab with various regulatory authorities in the Licensed Territory, (b) milestone payments tied to achievement of annual revenue from ivonescimab in the Licensed Territory and (c) royalty payments equal to low-double-digit percentage of annual revenues from ivonescimab in the Licensed Territory.

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.

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 Territories.

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 finding of PD-1 increases the binding affinity of VEGF and the binding of VEGF increases the affinity towards PD-1.

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.

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 tumor microenvironment with over 18 fold increased binding affinity to PD-1 in the presence of VEGF in vitro , and over 4 times increased binding affinity to VEGF in the presence of PD-1 in vitro .

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

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 .

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.

The intent of this design is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

In addition, the two Phase III clinical trials sponsored by the Company, ivonescimab is also being developed in China and Australia by Akeso in multiple solid tumors and has been dosed in more than 1,600 patients globally.

Based on data published by Akeso with a cut-off date of October 2023, ivonescimab treatment after a median follow-up time of approximately 25.8 months, was associated with an overall response rate (ORR) in a Phase II study in patients with NSCLC who have failed EGFR-TKI’s of 68.4%, a median Progression-Free Survival (“mPFS”) time period of 8.5 months, and a median Overall Survival (“mOS”) of 22.5 months when combined with combination chemotherapy (pemetrexed and carboplatin).

The Phase II study, AK112-201, Cohort 2, was considered to have demonstrated a tolerable safety profile and a low discontinuation rate for adverse events.

In a separate group in the same Phase II study, AK112-301 (Cohort 1) for NSCLC patients with squamous histology, ivonescimab, combined with carboplatin and paclitaxel, in first-line advanced or metastatic patients demonstrated a mPFS of 11.1 months.

Median overall survival was not reached after a median follow-up period of 21.0 months.

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

Summit plans to conduct its current clinical trials, as well as design and conduct additional clinical trial activities for ivonescimab in its Licensed Territory, to support and submit relevant regulatory filings.

Summit also plans to support additional study activities through its Investigator Initiated Study program.

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.

Product Pipeline

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Ivonescimab is currently being investigated in global Phase III clinical trials.

Phase I and II trials were completed by our partner Akeso.

This pipeline reflects clinical trials that have been initiated by Summit in its Licensed Territory.

HARMONi study (NCT05184712) is a multi-regional, registration-enabling clinical trial that we joined with Akeso, and for which we started initiating and activating sites in North America and Europe during 2023.

The first patient in our Licensed Territory was enrolled during the second quarter of 2023.

We plan to initiate additional sites in North America and Europe over the next few quarters.

We expect to complete enrollment during second half of 2024.

The co-primary endpoints for this study are Progression free survival (PFS) and Overall survival (OS).

We expect to combine data across all regions, including China, for assessing the results.

HARMONi-3 study (NCT05899608) is a phase III, is multi-regional, registration-enabling clinical trial for which we initiated activating sites in North Americas and China during fourth quarter of 2023.

We plan to initiate additional sites in North America, China, European countries, Japan and several other countries through early 2025.

Our plan to initiate in new countries and sites is dependent upon the timing and requirements for getting the regulatory approval of the clinical trial applications with the respective regulatory authorities and approvals from central or local independent review boards.

We may decide to modify our plans to go in certain regions or countries based on the timelines and requirements from the respective regulatory regions.

We commenced patient enrollment in the HARMONi-3 study during fourth quarter of 2023.

The primary endpoint for this study is Overall survival (OS).

In Q4 2023 we began collaborating with multiple institutions globally and opened our investigator initiated study program across several disease areas.

In addition, our partners at Akeso are sponsoring multiple, ongoing Phase II and III clinical trials in NSCLC and other cancers outside of our Licensed Territory.

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 our Licensed Territory.

Status of Anti-Infectives Pipeline

Discuva Platform

In December 2017, we acquired Discuva Limited, a privately held United Kingdom-based company.

Through this acquisition, we obtained a bacterial genetics platform and a suite of software-based technologies (collectively termed our “Discuva Platform”), which facilitate the discovery and development of new mechanism antibiotics.

Our Discuva Platform can be used to identify new bacterial targets for drug discovery, understand the mechanism of action of small molecules targeting varying types of bacteria and select the most optimal preclinical candidates, including those with the least propensity to develop bacterial resistance.

On January 20, 2023, we announced that, given the License Agreement that we entered into in December 2022 and the shift in Company’s focus to oncology, we will cease further investment in the Discuva platform and evaluate further options for the use of the Discuva Platform.

See Note 13 to our consolidated financial statements contained in this Annual Report on Form 10-K for further details.

Phase I and II trials were completed by or are ongoing with our partner Akeso.

This pipeline reflects Phase III clinical trials that have been or are planned to be initiated by Summit in its Licensed Territory.

HARMONi study (NCT05184712) is a Phase III, multi-regional, potentially registration-enabling clinical trial, which enrolled patients in North America, Europe, and China.

Patients enrolled in China were also enrolled as a part of the HARMONi-A study.

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

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.

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.

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

The key competitive factors affecting the success of our product candidates are

likely to be their efficacy, safety, convenience, price and availability of coverage and reimbursement from government and other third-party payors.

The key competitive factors affecting the success of our product candidates are likely to be their efficacy, safety, convenience, price and availability of coverage and reimbursement from government and other third-party payors.

Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do.

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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 (SMT112)

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

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:

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 our Licensed Territory.

There are no known approved PD-1/VEGF bispecific antibodies that are further advanced in clinical trial development or approved in the territories in which we have licensed ivonescimab.

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

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.

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”).

There are currently no known approved PD-1/VEGF bispecific antibodies that are further advanced in clinical trial development or approved in the territories in which we have licensed ivonescimab.

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.

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.

Currently, the most commonly used treatments for NSCLC are several immuno-oncology drugs and chemotherapies, administered either individually as monotherapy, in combination with each other, or in combination with other approved therapeutics.

NSCLC treatment regimens vary due to several factors, including genetic mutations and progression of disease.

In addition to various chemotherapies, several immunotherapies have been approved by the FDA for these treatments, including, but not limited to pembrolizumab, atezolizumab, nivolumab, durvalumab, and ipilimumab.

There are anti-angiogenic therapies which are approved for the treatment of certain lung cancers, including bevacizumab and ramucirumab.

In addition, there are several targeted therapies that have also been approved, including, but not limited to, osimertinib, adagrasib, and alectinib.

Beyond currently approved therapies, several potential therapeutics are in various stages of development and clinical trials for the treatment of NSCLC, including late-stage candidates which have recently released Phase III clinical trial data in NSCLC in 2023, such as Daiichi Sankyo and AstraZeneca’s datopotamab deruxetecan and Johnson & Johnson’s amivantamab and lazertinib.

Finally, there are candidates in various stages of ongoing clinical trials for NSCLC, including Daiichi Sankyo and Merck with patritumab deruxtecan and AstraZeneca’s volrustomig, each currently enrolling in Phase III clinical trials.

Currently, the most commonly used treatments for first-line NSCLC without genomic alterations are several immuno-oncology drugs and chemotherapies, administered either individually as monotherapy, in combination with each other, or in combination with other approved therapeutics.

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).

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.

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, ridinilazole or SMT-738.

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 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.

In connection with the License Agreement, we have also agreed to enter into the Supply Agreement with Akeso, pursuant to which we agree to purchase a certain portion of drug substance for clinical and commercial.

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

We have engaged with third-parties to initiate transfer of relevant know-how and potentially establish them as second source supplier of ivonescimab.

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

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 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, to operate without infringing the proprietary rights of others and to prevent others from infringing our proprietary rights.

We have obtained and maintain proprietary protection for our antibiotic 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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Ivonescimab Program .

Following the completion of the License and Collaboration Agreement with Akeso, Summit has in-licensed the rights to various Akeso patent applications directed to ivonescimab in specific countries and has rights to control prosecution of such in-licensed intellectual property in these specific countries in collaboration with Akeso.

The collaboration has 1 patent issued with 14 pending and we expect that these patent applications (assuming the applications proceed to grant) will provide patent coverage for the program until 2042.

Discuva Platform Technology.

Our Discuva Platform technology is currently protected by 14 granted U.S.

and foreign patents.

We expect patent protection for this portfolio to expire in 2032.

Ridinilazole Program .

Our ridinilazole program is currently protected by 96 granted U.S.

and foreign patents, with 34 pending patent applications.

Our patent portfolio for ridinilazole includes patents and patent applications directed to composition of matter, polymorphic forms, methods of manufacture and use and formulation subject matter.

We expect that our existing patents and patent applications (assuming the applications proceed to grant) will provide patent coverage for our ridinilazole program until 2043.

SMT-738 Program .

Our SMT-738 program currently has 14 granted patents and 29 patent applications pending worldwide, directed to the composition of matter.

We anticipate that our existing portfolio (assuming the applications proceed to grant) will provide patent coverage for our SMT-738 program until 2042.

Following the completion of the License Agreement with Akeso, we have in-licensed the rights to various Akeso patents and patent applications covering ivonescimab and related compositions of matter and methods of manufacture/use in the Licensed Territory and have rights to control prosecution of such in-licensed intellectual property in the Licensed Territory in collaboration with Akeso.

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.

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 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.

We also seek to preserve the integrity and confidentiality of our data, trade secrets and know-how by maintaining physical security of our premises and physical and electronic security of our information technology systems.

Summit, in working with Akeso, is in the process of selecting a name for ivonescimab, which we will pursue protection for as a trademark in licensed Summit countries.

We are in the process of selecting a name for ivonescimab, which we will pursue protection for as a trademark in the Licensed Territory.

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 that we infringe or otherwise violate the intellectual property rights of third parties.

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”.

Other Material Agreements

The following material agreements relate to our commitments and obligations with respect to ridinilazole and SMT-738 only.

The entry into the License Agreement represents a significant change in the Company’s strategy.

All prior development and marketing activities relating to ridinilazole have been terminated and all business activities related to anti-infectives are being reviewed for partnership opportunities for potential further development.

In September 2017, we were awarded a contract from the Biomedical Advanced Research and Development Authority (“BARDA”), part of the Office of the Assistant Secretary for Preparedness and Response at the United States Department of Health and Human Services, to fund, in part, the clinical and regulatory development of ridinilazole for the treatment of infections caused by C.

The contract provides for a cost-sharing arrangement under which BARDA funded a specified portion of estimated costs for the continued clinical and regulatory development of ridinilazole for CDI.

Under this cost sharing arrangement, we were responsible for a portion of the costs associated with each segment of work, including any costs in excess of the estimated amounts.

The awarded contract, as amended in 2019 and 2020, provided for total award up to $72.5M, and total amount of committed funding to $62.4 million.

As of December 31, 2023, based on translation of historical foreign currency amounts in the period, the Company has recognized $59.2 million of cumulative income since contract inception.

As a result of the Company’s decision to not pursue further internal clinical development of ridinilazole and seek partners or a divestiture related to ridinilazole as a path forward for the clinical development of the asset, the Company recorded expenses for the remaining clinical trial costs associated with the close out activities of ridinilazole and recognized the remainder of the deferred income that had been received from BARDA prior to the expenses being recognized during the third quarter of 2022.

Wellcome Trust

In October 2012, we entered into a translation award funding agreement with the Wellcome Trust Limited, as trustee of the Wellcome Trust, in order to support a Phase I and a Phase II clinical trial of ridinilazole for the treatment of CDI, for which we received $6.3 million.

The translation award funding agreement followed an initial funding agreement we and the Wellcome Trust entered into in October 2009, under which we received $3.7 million for preclinical development of CDI antibiotics.

In October 2017, we entered into a revenue sharing agreement with the Wellcome Trust.

Under the terms of the revenue sharing agreement upon commercialization of ridinilazole the Wellcome Trust is eligible to receive a share of the net revenues that we, our affiliates, licensees or third-party collaborators receive from commercial sales, and a one-time milestone payment of a specified amount if cumulative net revenues that we our affiliates, licensees or third-party collaborators receive exceed a specified amount.

In addition, if a third party commercializes ridinilazole following the first commercial sale by such third party, the Wellcome Trust is eligible to receive a one-time milestone payment of a share of the aggregate amount of any pre-commercial payments we receive from third-party licensees prior to such commercial sale and in the event of an assignment or sale of the assets or intellectual property pertaining to ridinilazole, the net proceeds we receive from such assignment or sale would be treated as net revenue under the revenue sharing agreement.

Eurofarma Laboratórios S.A.

In December 2017, we entered into an exclusive license and commercialization agreement with Eurofarma, pursuant to which we granted Eurofarma the exclusive right to commercialize ridinilazole in specified countries in South America, Central America and the Caribbean (the licensed territory).

We have retained commercialization rights in the rest of the world.

Under the terms of the license agreement, we received an upfront payment of $2.5 million.

In 2020 and 2021, we achieved the first and second enrollment targets and earned $2.25 million We are also entitled to receive additional development, commercial and sales milestones and have a provision to enter into commercial supply agreement.

With the closeout of ridinilazole clinical trials, at this time, we are not anticipating any future payments from Eurofarma under this agreement.

Under the license agreement, Eurofarma is responsible for all costs related to obtaining regulatory approval of ridinilazole in the licensed territory and is obligated to use commercially reasonable efforts to file applications for regulatory approval in specified countries in the licensed territory within a specified time period after we have filed an application for regulatory approval, or obtained regulatory approval, for ridinilazole in a jurisdiction where we retain commercial rights.

We retain sole responsibility for the clinical development of ridinilazole in all countries and are responsible for all costs related to obtaining regulatory approval for ridinilazole outside of the licensed territory.

University College London

On March 23, 2010, we entered into a collaborative research agreement with the School of Pharmacy, University of London which was later novated on November 28, 2011, by the School of Pharmacy to University College London.

As part of this agreement, and in consideration of their role in the development of the initial compound series from which ridinilazole was later identified, we agreed to pay the School of Pharmacy (now University College London) a low single-digit share of all revenue received by us with respect to ridinilazole, including any pre-commercial licensing revenue, up to a maximum of $1.2 million.

To date, we have paid $0.1 million under this agreement.

In May 2021, we announced the selection of a new preclinical candidate, SMT-738, which originated from the DDS-04 series.

SMT-738 has been under development to combat multi-drug resistant infections, specifically Carbapenem-resistant Enterobacteriaceae (“CRE”) infections.

Simultaneously, Summit has received a sub-award from CARB-X to progress SMT-738 through preclinical development and an option to continue into Phase Ia clinical studies.

The award commits initial non-dilutive funding of up to $4.1 million for the preclinical phase, with the potential for a further $3.7 million available for the Phase Ia clinical phase upon successfully achieving key preclinical development milestones.

During the quarter ended September 30, 2022, CARB-X announced changes to its funding arrangements and terms and conditions.

As a result, the current arrangement concluded as of June 30, 2022 however, we have the ability to recognize revenue for any milestone payments related to work incurred subsequent to this date in accordance with this agreement.

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 the FDA under the Federal Food, Drug, and Cosmetic Act (“FDCA”) and its implementing regulations, as well as other regulatory bodies in the United States, Europe and other countries.

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.

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

The failure 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 refusal by the FDA to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of letters, product recalls, product seizures, total or partial suspension of production 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 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.

” 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;

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

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

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

• 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;

• 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”);

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• 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;

• payment of user fees and securing FDA approval of the NDA/BLA;

• 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;

• 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

Before an applicant begins testing a compound with potential therapeutic value in humans, the product candidate enters the preclinical testing stage.

Preclinical studies include laboratory evaluation of the purity and stability of the API, and the formulated drug or drug product, as well as in vitro and animal studies to assess the safety and activity of the drug for initial testing in humans and to establish a rationale for therapeutic use.

The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations.

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

Preclinical studies include laboratory evaluation of the purity and stability of the API and the formulated drug product, as well as in vitro and animal studies to assess the safety and activity of the drug for initial testing in humans and to establish a rationale for therapeutic use.

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.

Companies usually must complete some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, and must also develop additional information about the synthesis and physical characteristics of the investigational product and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

Prior to submission of an NDA or BLA, a manufacturer must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

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

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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 an investigational clinical trial and a request for FDA authorization to administer an investigational drug to humans.

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.

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.

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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 whenever 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.

A partial clinical hold is a delay or suspension of only part of the clinical work requested under the IND.

For example, a specific protocol or part of a protocol or new patient enrollment is not allowed to proceed, while other protocols or already enrolled patients may continue.

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.

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When a foreign clinical study is conducted under an IND, all FDA IND requirements must be met unless waived.

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 investigational new drug application as support for an IND or a new drug application.

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

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.

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

In addition to the foregoing IND requirements, an IRB/Ethics Committee (“EC”) representing each institution participating in the clinical trial must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the study at least annually.

In addition to the foregoing IND requirements, an IRB/Ethics Committee (“EC”) representing each institution participating in any clinical trial for which data is intended to be submitted to FDA must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the study at least annually.

The IRB/EC must review and approve, among other things, the study protocol and informed consent information to be provided to study subjects.

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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 organized by the trial sponsor, known as a data safety monitoring board or committee.

This group provides authorization for whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the study.

Suspension or termination of development 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 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.

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 Institutes of Health (“NIH”), for public dissemination on its ClinicalTrials.gov website.

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:

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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 or 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 settings);

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

intermediate-size patient populations;

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

Running clinical trials that can support regulatory approvals is

the best way to ultimately ensure wide access for patients to our product candidates.

At this point in the development, we cannot support any use of our product candidates outside of clinical trials.

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.

Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program.

There is no obligation for a drug manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act, but the manufacturer must develop an internal policy and respond to patient requests according to that policy.

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.

There is no obligation for a drug manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act.

Human Clinical Trials in Support of an NDA/BLA

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all research subjects provide their informed consent in writing before their participation in any clinical trial.

Clinical trials are conducted under written study protocols detailing, among other things, the inclusion and exclusion criteria, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all research subjects provide their freely given informed consent in accordance with FDA regulations and applicable local laws before their participation in any clinical trial.

Clinical trials are conducted under written study protocols detailing, among other things, the inclusion and exclusion criteria, the objectives of the study, the parameters to be used in monitoring the study and the safety and effectiveness criteria to be evaluated.

Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined:

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The investigational drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

The investigational drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product.

These clinical trials are commonly referred to as “pivotal” studies, which denotes a study that presents the data that the FDA or other relevant regulatory agency will use to determine the primary basis of whether or not to approve a product candidate.

Progress reports of the clinical trials must be submitted at least annually to the FDA and more frequently if serious adverse events occur.

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

The investigational drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate sufficient data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product.

These clinical trials are commonly referred to as “pivotal” studies, which denotes a study that is intended to generate data that will be relied upon by the FDA or another relevant regulatory agency as the primary basis for approval of a product candidate.

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:

serious and unexpected suspected adverse reactions;

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

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

Similarly, an IRB/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 drug has been associated with unexpected serious harm to patients.

The FDA/HA will typically inspect one or more clinical sites to assure compliance with GCP and the integrity of the clinical data submitted.

Under the Pediatric Research Equity Act (“PREA”) of 2003, an NDA or supplement thereto must contain data that are adequate 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.

With enactment of the Food and Drug Administration Safety and Innovation Act (“FDASIA”), in 2012, sponsors must also submit pediatric study plans prior to the assessment data.

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

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.

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.

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.

The applicant, the FDA, and the FDA’s internal review committee must then review the information submitted, consult with each other, and agree upon a final plan.

The FDA or the applicant may request an amendment to the plan at any time.

The FDA or the applicant may request an amendment to the pediatric plan at any time.

A sponsor must submit an initial pediatric study plan, if required under PREA, no later than either 60 calendar days after the date of the end-of-phase II meeting or such other time as agreed upon between FDA and the sponsor.

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Submission of an NDA/BLA to the FDA

Assuming successful completion of required clinical testing and other requirements, the results of the preclinical studies and clinical trials, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA/BLA requesting approval to market the drug product for one or more indications.

Under federal law, the submission of most NDAs/BLAs is subject to an application user fee, which for federal fiscal year 2023 is $3,242,026 for an application requiring clinical data.

Assuming successful completion of required clinical investigations and other requirements, the results of the preclinical studies and clinical trials, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA or BLA requesting approval to market the drug product for one or more indications.

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 2025 is $4,310,002 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.

Following submission of an application, the FDA conducts a filing review of an NDA/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/BLA for filing.

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.

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

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

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

Under that agreement, 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.

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.

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.

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

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

Under the FDA Reauthorization Act of 2017, the FDA must implement a protocol to expedite review of responses to inspection reports pertaining to certain applications, including applications for products in shortage or those for which approval is dependent on remediation of conditions identified in the inspection report.

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

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

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The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Fast Track, Breakthrough Therapy, Priority Review and Regenerative Advanced Therapy Designations

Fast Track, Breakthrough Therapy and Priority Review

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 advanced therapy designation.

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.

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/BLA is complete.

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.

This rolling review may be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a fast-track product may be effective.

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/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.

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.

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.

Second, a product may be designated as a breakthrough therapy if it is intended, either alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

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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.

Finally, with passage of the 21st Century Cures Act, or Cures Act, in December 2016, Congress authorized the FDA to accelerate review and approval of antibacterial products via the limited-population antibacterial drug (“LPAD”) pathway.

The LPAD pathway provides a unique mechanism for the Food and Drug Administration to review and approve new antibacterial drugs that address unmet medical needs for specific, limited populations of patients - those with serious and life-threatening bacterial infections that are resistant to current treatments.

This targeted approach would make antibiotic development more feasible by allowing for smaller clinical development programs that are focused on the limited, high-risk populations that would use these new antibiotics, instead of on more general populations that can be treated with existing medicines.

LPAD would also make antibiotic development more feasible by enabling FDA to assess these drugs based on the unique balance of benefits they offer versus risks they present to the limited number of patients they are intended to treat - specifically, patients who have few or no other treatment options.

Product candidates that qualify for LPAD review may simultaneously qualify for one or more of FDA’s expedited review programs.

Accelerated Approval Pathway

The FDA may grant accelerated approval to a drug for a serious or life-threatening condition that provides meaningful therapeutic advantage to patients over existing treatments based upon a determination that the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.

The FDA may also grant accelerated approval for such a drug when

the product has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality (“IMM”), and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

The FDA may also grant accelerated approval for such a drug when the product has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality (“IMM”), and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

Drugs granted accelerated approval must meet the same statutory standards for safety and effectiveness as those granted traditional approval.

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

The FDA’s Decision on an NDA/BLA

On the basis of the FDA’s evaluation of the NDA/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.

The Food and Drug Omnibus Reform Act of 2022 (“FDORA”) 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.

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.

While this draft guidance is not legally binding, sponsors seeking consideration of a product for accelerated approval typically adhere to the FDA’s guidance to enhance the likelihood of their products qualifying for accelerated approval.

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.

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

A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application.

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

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.

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Post-Approval Requirements

Drugs manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record keeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse experiences with the product.

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 products, as well as new application fees for supplemental applications with clinical data.

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.

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

For example, the FDA may require post-marketing testing, including clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies.

The drug manufacturers are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements.

Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented.

For example, the FDA may require post-marketing testing, including post-marketing clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and some state agencies and submit to FDA an annual listing of products manufactured for commercial distribution at each facility.

Drug manufacturers are subject to periodic announced or unannounced inspections by the FDA and these state agencies for compliance with cGMP and other regulatory requirements.

Changes to the manufacturing process for a drug product are strictly regulated and often require prior FDA approval before being implemented.

FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use.

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

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

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.

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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• restrictions on the marketing or manufacturing of the product, suspension of the approval, complete withdrawal of the product from the market or product recalls;

• fines, warning letters or holds on post-approval clinical trials;

• fines, warning letters or imposition of clinical holds on post-approval clinical trials;

• refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals;

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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 prescribing information.

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.

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 the promotion of off-label uses.

It may be permissible, under very specific, narrow conditions, for a manufacturer to engage in non-promotional, non-misleading communication regarding off-label information, such as distributing scientific or medical journal information.

If a company is found to have promoted off-label uses, it may become subject to adverse public relations and administrative and judicial enforcement by the FDA, the DOJ, or the Office of the Inspector General of the Department of Health and Human Services, as well as state authorities.

This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products.

The federal government has levied large civil and criminal fines against companies for alleged improper promotion, and has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.

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.

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.

If a company is alleged to have promoted a product for off-label uses, it may become subject to investigations, adverse public relations and administrative and judicial enforcement by the FDA, the DOJ, or the Office of the Inspector General of the Department of Health and Human Services, as well as state authorities.

In addition, an action may be brought on behalf of the government by a qui tam relator under the Federal False Claims Act asserting that a manufacturer’s communications regarding an off-label use of its product caused submission of false claims for payment by a government health care program.

These actions could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products.

These actions have resulted in the imposition of large civil and criminal fines and penalties against, and substantial settlements by, companies for alleged improper promotion.

As a result of these actions, companies have entered into consent decrees, non-prosecution agreements, deferred prosecution agreements or corporate integrity agreements under which specified promotional conduct is changed or curtailed, and substantial compliance obligations are imposed on manufacturers.

In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act (“PDMA”), and its implementing regulations, as well as the Drug Supply Chain Security Act (“DSCSA”), which regulate the distribution and tracing of prescription drug samples at the federal level, and set minimum standards for the regulation of distributors by the states.

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Pediatric Exclusivity

Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, including the non-patent and orphan exclusivity.

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

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.

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 additional protection is granted.

If reports of requested pediatric studies are submitted to and accepted 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 application.

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.

Patent Term Restoration and Extension

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Patent and Trademark Office (“USPTO”) reviews and approves the application for any patent term extension or restoration in consultation with the FDA.

Orphan-Drug Designation and Exclusivity

Under the Orphan Drug Act, FDA may grant orphan drug designation to a drug or biologic product intended to treat a rare disease or condition.

A rare disease or condition is defined as one that either affects fewer than 200,000 individuals in the United States or for which a manufacturer has no reasonable expectation that the cost of developing and making the product available in the United States for the disease or condition will be recovered from sales of the product.

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 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.

If a product that has orphan drug designation subsequently receives the first FDA approval for the rare disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity.

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.

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.

Regulation Outside the United States

In order to market any product outside of the United States, a company must also comply with numerous and varying regulatory requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing, among other things, clinical trials, marketing authorization, commercial sales and distribution of drug products.

In order to market any product outside of the United States, a company must also comply with numerous and varying regulatory requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing, among other things, clinical trials, marketing authorization, promotion, commercial sales and distribution of drug products.

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

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Clinical Trial Approval

The Clinical Trials Directive 2001/20/EC, 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 European Union.

Under this system, an applicant must obtain prior approval from the competent national authority of the

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 Directive 2001/20/EC, Directive 2005/28/EC, where relevant the implementing national provisions of the individual E.U.

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.

In April 2014, the new Clinical Trials Regulation, (E.U.) No 536/2014 (Clinical Trials Regulation) was adopted.

The Regulation was published on June 16, 2014, but has not yet become effective.

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

Member States, repealing the current Clinical Trials Directive 2001/20/EC and replacing any national legislation that was put in place to implement the Directive.

Conduct of all clinical trials performed in the European Union will continue to be bound by currently applicable provisions until the new Clinical Trials Regulation becomes applicable.

The extent to which ongoing clinical trials will be governed by the Clinical Trials Regulation will depend on when the Clinical Trials Regulation becomes applicable and on the duration of the individual clinical trial.

If a clinical trial continues for more than three

years from the day on which the Clinical Trials Regulation becomes applicable, the Clinical Trials Regulation will at that time begin to apply to the clinical trial.

The new Clinical Trials Regulation aims to simplify and streamline the approval of clinical trials in the European Union.

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.

Member States.

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

The main characteristics of the Regulation include:

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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).

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

submitted (“Concerned Member States”).

Part II is assessed separately by each Concerned Member State.

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However, overall related timelines will be defined by the Clinical Trials Regulation.

As in the United States, similar requirements for posting clinical trial information are present in the European Union (EudraCT) website:

https://eudract.ema.europa.eu/ and in other countries.

As in the United States, similar requirements for posting clinical trial information are present in the E.U.

and in other countries.

Marketing Authorization

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A marketing authorization may be granted only to an applicant established in the E.U.

Regulation (EC) No 1901/2006 provides that prior to obtaining a marketing authorization in the European Union, applicants have to demonstrate compliance with all measures included in an EMA-approved Paediatric Investigation Plan (“PIP”), covering all subsets of the pediatric population, unless the EMA has granted (1) a product-specific waiver, (2) a class waiver or (3) a deferral for one or more of the measures included in the PIP.

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid across the European Economic Area (i.e., the European Union as well as Iceland, Liechtenstein and Norway).

prior to obtaining a marketing authorization in the E.U., applicants have to demonstrate compliance with all measures included in an EMA-approved Paediatric Investigation Plan (“PIP”), covering all subsets of the pediatric population, unless the EMA has granted (1) a product-specific waiver, (2) a class waiver or (3) a deferral for one or more of the measures included in the PIP.

These requirements are discussed in more detail below.

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid across the European Economic Area (i.e., the E.U.

as well as Iceland, Liechtenstein and Norway).

Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products and products with a new active substance indicated for the treatment of certain diseases, including products for the treatment of cancer.

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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 European Union, 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 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.

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 it is possible that the CHMP can revert to the standard time limit for the centralized procedure if it considers 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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Member States and chaired by a non- voting European Commission representative.

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 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.

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 obtaining the comprehensive clinical data required for an application for a full marketing authorization.

Such conditional marketing authorizations may be granted for product candidates (including medicines designated as orphan medicinal products), if (i) the risk-benefit balance of the product candidate is positive, (ii) it is likely that the applicant will be in a position to provide the required comprehensive clinical trial data, (iii) the product fulfills an unmet medical need and (iv) the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required.

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.

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

(i) the risk-benefit balance of the product candidate is positive, (ii) it is likely that the applicant will be in a position to provide the required comprehensive clinical trial data, (iii) the product fulfills an unmet medical need and (iv) the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required.

A conditional marketing authorization may contain specific obligations to be fulfilled by the marketing authorization holder, including obligations with respect to the completion of ongoing or new studies, and with respect to the collection of pharmacovigilance data.

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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 rules expressly permit the E.U.

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.

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Unlike the centralized authorization procedure, the decentralized marketing authorization procedure requires a separate application to, and leads to separate approval by, the competent authorities of each E.U.

Member State in which the product is to be marketed.

Member State in which the product is to be marketed (these are known as the “concerned” Member States).

This application is identical to the application that would be submitted to the EMA for authorization through the centralized procedure.

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Member State.

Regulatory Data Protection in the European Union

In the European Union, innovative medicinal products approved on the basis of a complete independent data package qualify for eight years of data exclusivity upon marketing authorization and an additional two years of market exclusivity pursuant to Directive 2001/83/EC.

Regulatory Data Protection in the E.U.

In the E.U., innovative medicinal products approved on the basis of a complete independent data package qualify for eight years of data exclusivity after grant of the marketing authorization and an additional two years of market exclusivity pursuant to Directive 2001/83/EC.

Regulation (EC) No 726/2004 repeats this entitlement for medicinal products authorized in accordance to the centralized authorization procedure.

Data exclusivity prevents applicants for authorization of generics of these innovative products from referencing the innovator’s data to assess a generic (abridged) application for a period of eight years.

During an additional two-year period of market exclusivity, a generic marketing authorization application 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 exclusivity.

Data exclusivity prevents applicants for authorization of generics of these innovative products, from referencing the innovator’s data to assess a generic (or abridged) application for a period of eight years.

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

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.

Orphan Drug Designation and Exclusivity

Regulation (EC) No.

141/2000, as implemented by Regulation (EC) No.

847/2000 provides that a medicine can be designated as an orphan medicinal product by the European Commission if its sponsor can establish:

that the product is intended for the diagnosis, prevention or treatment of (1) a life-threatening or chronically debilitating condition affecting not more than five in ten thousand persons in the E.U.

when the application is made, or (2) a life-threatening, seriously debilitating or serious and chronic condition in the E.U.

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.

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.

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.

Marketing authorization may also be granted to a similar medicinal product with the same orphan indication if this product is shown to be safer, more effective or otherwise clinically superior to the original orphan medicinal product.

The period of market exclusivity may, in addition, be reduced to six years if it can be demonstrated on the basis of available evidence that the original orphan medicinal product (a) no longer satisfies the original designation criteria;

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

Periods of Authorization and Renewals

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The European Commission or the competent authorities of the E.U.

Member States decide on justified grounds relating to pharmacovigilance, to proceed with one further five-year period of marketing authorization.

Member States decide on justified grounds relating to pharmacovigilance, whether to proceed with one further five-year period of marketing authorization.

Once subsequently definitively renewed, the marketing authorization shall be valid for an unlimited period.

Any authorization which is not followed by the actual placing of the medicinal product on the E.U.

market (in case of centralized procedure) or on the market of the authorizing E.U.

market (in the case of the centralized procedure) or on the market of the authorizing E.U.

Member State within three years after authorization ceases to be valid (the so-called sunset clause).

Pediatric Studies

Prior to obtaining a marketing authorization in the European Union, applicants have to demonstrate compliance with all measures included in an EMA-approved Paediatric Investigation Plan, covering all subsets of the pediatric population, unless the EMA has granted a product-specific waiver, a class waiver, or a deferral for one or more of the measures included in the PIP.

Prior to obtaining a marketing authorization in the E.U., applicants have to demonstrate compliance with all measures included in an EMA-approved Paediatric Investigation Plan, covering all subsets of the pediatric population, unless the EMA has granted a product-specific waiver, a class waiver, or a deferral for one or more of the measures included in the PIP.

The respective requirements for all marketing authorization procedures are set forth in Regulation (EC) No 1901/2006, which is referred to as the Paediatric Regulation.

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The PDCO may also grant waivers when development of a medicine in children is not needed or is not appropriate, such as for diseases that only affect the elderly population.

Before a marketing authorization application can be filed, or an existing marketing authorization can be amended, the EMA determines that companies actually comply with the agreed studies and measures listed in each relevant PIP.

Before an MAA can be filed, or an existing marketing authorization can be amended, the EMA determines that companies actually comply with the agreed studies and measures listed in each relevant PIP.

Regulatory Requirements after a Marketing Authorization has been Obtained

In case an authorization for a medicinal product in the European Union is obtained, the holder of the marketing authorization is required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products.

In case an authorization for a medicinal product in the E.U.

is obtained, the holder of the marketing authorization is required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products.

These include:

• Compliance with the European Union’s stringent pharmacovigilance or safety reporting rules must be ensured.

• Compliance with the E.U.’s stringent pharmacovigilance or safety reporting rules.

These rules can impose post-authorization studies and additional monitoring obligations;

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These requirements include compliance with E.U.

cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients,

including the manufacture of active pharmaceutical ingredients outside of the European Union with the intention to import the active pharmaceutical ingredients into the European Union;

• The marketing and promotion of authorized drugs, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the European Union notably under Directive 2001/83EC, as amended, and E.U.

cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the E.U.

with the intention to import the active pharmaceutical ingredients into the E.U.;

• The marketing and promotion of authorized medicines, including industry-sponsored continuing medical education and advertising directed toward the prescribers of medicines and/or the general public, are strictly regulated in the E.U.

notably under Directive 2001/83EC, Regulation (EC) 726/2004 and E.U.

Member State laws.

Direct-to- consumer advertising of prescription medicines is prohibited across the European Union.

General Data Protection Regulation

The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the European Union, including personal health data, is subject to the E.U.

General Data Protection Regulation (“GDPR”), which became effective on May 25, 2018.

The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors.

The GDPR also imposes strict rules on the transfer of personal data to countries outside the European Union, including the U.S., and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater.

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

Compliance with the GDPR will be a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance.

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

Pricing Decisions for Approved Products

In the European Union, pricing and reimbursement schemes vary widely from country to country.

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 European Union 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.

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 European Union have increased the amount of discounts 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 European Union.

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.

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Patent Term Extension

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

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

Member State and the granted certificates are valid only in the Member State of grant.

An application has to be made by the patent owner within six months of the first marketing authorization being granted in the European Union (assuming the patent in question has not expired, lapsed or been revoked) or within six months of the grant of the patent (if the marketing authorization is granted first).

An application has to be made by the patent owner within six months of the first marketing authorization being granted in the E.U.

(assuming the patent in question has not expired, lapsed or been revoked) or within six months of the grant of the patent (if the marketing authorization is granted first).

In the context of SPCs, the term “product” means the active ingredient or combination of active ingredients for a medicinal product and the term “patent” means a patent protecting such a product or a new manufacturing process or application for it.

The duration of an SPC is calculated as the difference between the patent’s filing date and the date of the first marketing authorization, minus five years, subject to a maximum term of five years.

A six month pediatric extension of an SPC may be obtained where the patentee has carried out an agreed pediatric investigation plan, the authorized product information includes information on the results of the studies and the product is authorized in all member states of the European Union.

A six month pediatric extension of an SPC may be obtained where the patentee has carried out an agreed Pediatric Investigation Plan, the authorized product information includes information on the results of the studies and the product is authorized in all E.U.

Member States.

Brexit and the 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.

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 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.

Healthcare Law and Regulation

Health Care Providers and third-party payors play a primary role in the recommendation and prescription of drug products that are granted marketing approval.

Arrangements with providers, consultants, third-party payors and customers are subject to broadly applicable fraud and abuse, anti-kickback, false claims laws, patient privacy laws and regulations and other healthcare laws and regulations that may constrain business and/or financial arrangements.

Arrangements between drug product manufacturers and providers, consultants, third-party payors and customers are subject to broadly applicable fraud and abuse, anti-kickback, false claims laws, patient privacy laws and regulations, and other healthcare laws and regulations that may constrain business and/or financial arrangements.

Restrictions under applicable federal and state healthcare laws and regulations, include the following:

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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;

• the federal Health Insurance Portability and Accountability Act of 1996, or 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, and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, which impose obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;

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

• 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, 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;

• 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.

officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment;

• 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, 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, 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;

• 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.

Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.

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 not preempted by HIPAA, thus complicating compliance efforts.

Some state and local laws impose regulations restricting the activities of pharmaceutical manufacturers that sell products in the state.

Some of these laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and/or the relevant compliance guidance promulgated by the local, state or federal government.

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.

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.

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

Pharmaceutical Coverage and Reimbursement

In the United States and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs.

Significant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and other

government authorities.

In the United States and markets in many other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs.

Significant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and other government authorities.

Thus, even if a product candidate is approved, sales of the product will depend, in part, on the extent to which third-party payors, including government health programs in the United States such as Medicare and Medicaid, commercial health insurers and managed care organizations, provide coverage and establish adequate reimbursement levels for, the product.

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Third-party payors may limit coverage to specific products on an approved list, also known as a formulary, which might not include all of the approved products for a particular indication.

Other times, they will attempt to dictate the utilization of products to treat a disease via clinical guidelines or pathways.

In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, in addition to the costs required to obtain FDA or other comparable marketing approvals.

Nonetheless, product candidates may not be considered medically necessary or cost effective.

Nonetheless, product candidates may not be considered medically necessary or cost effective resulting in payers deciding to limit reimbursement of a product.

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.

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.

The containment of health care costs also has become a priority of federal, state and foreign governments and the prices of products have been a focus in this effort.

Governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products.

Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit a company’s revenue generated from the sale of any approved products.

Coverage policies and third-party reimbursement rates may change at any time.

Even if favorable coverage and reimbursement status is attained for one or more products for which a company or its collaborators receive marketing approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

There have been a number of federal and state proposals during the last few years regarding the pricing of pharmaceutical and biopharmaceutical products, limiting coverage and reimbursement for drugs and other medical products, government control and other changes to the healthcare system in the United States.

In March 2010, the United States Congress enacted the Affordable Care Act, or ACA, which, among other things, includes changes to the coverage and payment for drug products under government health care programs.

Among the provisions of the ACA of importance to our potential product candidates are:

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

• expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability;

• expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum rebate for both branded and generic drugs and revising the definition of “average manufacturer price,” or AMP, for calculating and reporting Medicaid drug rebates on outpatient prescription drug prices;

• addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;

• expanded the types of entities eligible for the 340B drug discount program;

• established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 70% as of January 1, 2019 point-of-sale-discount off the negotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;

• a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

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

In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress.

A Joint Select

Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs.

This includes aggregate reductions of Medicare payments to providers up to 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments, will remain in effect through 2027 unless additional Congressional action is taken.

In January 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

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

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

These 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 result in additional pricing pressures.

The demand for our products is predicated on our clinical trial strategy of attempting to achieve superiority against the standard-of-care.

If there are not adequate reimbursement levels, our business and results of operations could be adversely affected.

Pharmaceutical Price Reforms

The prices of pharmaceutical and biopharmaceutical products have been a focal point of federal, state, and foreign governments’ efforts to contain health care costs.

Most significantly, interest in the adoption and implementation of cost-containment programs, including price controls, mandated price negotiations, tenders based on perceived therapeutic equivalence, restrictions on reimbursement, and requirements for substitution of generic products, have increased.

Adoption of such price controls and cost-containment measures—including adoption of more restrictive policies in jurisdictions with existing controls and measures—could further limit the revenue a company might generate from the sale of an approved product, particularly if such measures result in more restrictive coverage or lower reimbursement from third party payors.

Prescription pharmaceutical pricing has been the subject of considerable discussion and activity in the United States on both the federal and state levels and from both political parties.

A number of foreign, federal, and state laws impose limitations on the pricing of pharmaceutical and biopharmaceutical products.

These laws may also impose controls that limit coverage and reimbursement for drugs and other medical products.

Recent approaches to contain pharmaceutical costs have varied and include—among other strategies—increasing transparency in pharmaceutical pricing, reviewing the relationship between pricing and manufacturer patient programs, and directly addressing the costs of pharmaceuticals in the Medicare and Medicaid programs.

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.

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.

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.

The “Medicare Drug Inflation Rebate Program,” which penalizes manufacturers for increasing prices of Medicare Part B and Medicare Part D drugs faster than the rate of inflation may also further impact industry pricing considerations for future products.

Changes stemming from the Part D benefit redesign may similarly impact downstream stakeholder behavior and formulary management practices that may influence pricing and the demand for certain drugs.

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.

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.

Certain of these states have submitted Section 804 Importation Program proposals and are awaiting FDA approval.

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.

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.

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.

A number of states, for example, require drug manufacturers and other entities in the drug supply chain, including health carriers, pharmacy benefit managers, wholesale distributors, to disclose information about pricing of pharmaceuticals.

Several states have also authorized the use of prescription drug affordability boards to impose price constraints on certain high-cost prescription drugs.

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.

General Data Protection Regulation and other Privacy Laws

We are subject to or affected by numerous data privacy and security obligations, that apply in Europe and other countries, including the European Economic Area’s (EEA’s) General Data Protection Regulation (“GDPR”).

Following the withdrawal of the United Kingdom from the EU, the U.K.

Data Protection Act 2018 was enacted and includes parallel obligations to those set forth by GDPR.

The GDPR is wide-ranging in scope and imposes numerous strict requirements on companies that process personal data, including heightened requirements on companies that process health and other sensitive data, such as requiring in many situations that a company obtain consent of individuals before processing their personal data.

Other examples of obligations imposed by the GDPR include providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, appointing a data protection officer, taking certain measures when engaging third-party processors, and providing notification of data breaches.

The GDPR also permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater.

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

The GDPR also imposes strict rules on the transfer of personal data to countries outside the EEA, including the U.S.

The transfer of personal data from the EEA to the U.S.

is generally restricted unless a company participates in the EU-U.S.

Data Privacy Framework or have otherwise implemented specific safeguards to protect the data.

Some privacy advocacy groups are interested in challenging these mechanisms, so the uncertainty surrounding what will constitute a legal cross-border transfer of data in the future may impact our business.

Compliance with the GDPR is a rigorous and time-intensive process that may increase the cost of doing business.

Moreover, failure to comply may lead to significant penalties or reputational harm.

Beyond the GDPR, there are privacy and data security laws in a growing number of countries around the world.

While many loosely follow the GDPR as a model, other laws contain different or conflicting provisions.

Human Capital

In order to be a competitive, innovative and successful Company, we believe it is critical to attract, engage, motivate and retain a dedicated, talented and innovative team of employees.

As part of these efforts, we strive to foster a diverse, equitable and inclusive community, invest in continuous learning and development, offer a competitive compensation and benefits program and provide a safe and healthy workplace.

Our success starts and ends with having the best talent and, as a result, we are focused on attracting, developing, and engaging our employees.

In 2022, we continued to strengthen the team by attracting a number of world class leaders with successful track records into the Company, all of our executive positions are now filled with proven leaders.

Summit employees are the cornerstone of our strategy.

We believe our ability to hire, retain and develop top talent is key in achieving our long-term strategic goals.

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.

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 or sexual orientation.

As of December 31, 2024, we had 159 total employees.

Of our total workforce, approximately 68% work in research and development, and 32% work in finance, legal, information technology, general management and other administrative functions.

Approximately 90% and 10% of our workforce is located in the U.S.

and the U.K., respectively.

In 2023, we once again made challenging demands of our employees and they have responded with dedication and enthusiasm.

In August 2023, Summit launched an engagement survey, in which 91% of employees responded.

The results of this survey showed our employees to be well engaged, with a strong team spirit and strongly aligned to the Company’s mission.

Approximately 92.5% of our workforce is in the United States and approximately 7.5% is outside of the United States.

Compensation and Benefits

We provide competitive compensation and benefits programs to attract, motivate and retain our employees.

We regularly review our compensation practices and analyze the equity of compensation decisions for individual employees and our workforce as a whole.

In addition to competitive compensation, we provide generous benefits including employer contributions to pension/401k plans, an employee stock purchase plan, health and welfare programs and benefits, and paid vacation.

We are committed to ensuring that our total compensation packages are competitive while supporting our business plans and strategies.

Diversity, Equity and Inclusion

We are committed to embedding a culture of diversity, equity and inclusion across our Company.

We believe that diversity of gender, age, ethnicity, sexual orientation, culture, education, background and experience fuels innovation and enables our employees to succeed.

This includes ensuring opportunity for all and embraces the positive effect that our diverse workforce brings.

We do not tolerate any form of discrimination and our employment policies and practices focus on ensuring that all our employment processes are free from discrimination or harassment on any grounds.

Approximately 57% of our employees are female and 47% of our executive team is female.

To address a competitive and dynamic labor market and attract and retain talent, Summit provides a comprehensive total rewards package which includes market competitive salaries, stock options, an annual performance discretionary bonus, employer contributions to pension/401(k) plans, an employee stock purchase plan, paid vacations, holidays and a hybrid work schedule.

Summit visits its compensation practices and reviews its benefit programs annually, adjusting as needed to ensure that its total reward offerings continue to address the needs of its employees and compensation packages assist Summit in hiring and retaining top-talent to meet business goals and objectives.

Culture and Engagement

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:

Integrity – to uphold the highest standards;

Passion for Excellence – a learning mindset embracing change to drive success;

Purposeful Urgency -unwavering commitment to fulfill our mission to patients pursuing audacious goals;

Accountability – assuming responsibility for our actions and outcomes;

Collaboration – the power of teamwork;

and Our Commitment to People – prioritizing patients and the health and safety of every Summit colleague actively providing impactful growth opportunities.

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.

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

Learning and Development

We are committed to investing in learning and development for our employees.

Our employees have access to online training courses which cover a wide range of technical and business topics to help them develop their professional skills and explore other areas as they plan for their career and personal growth.

Our performance management process includes timely performance feedback and career development discussions which are critical to each employee’s continued growth and development within the organization.

We are committed to investing in learning and development for our employees and provide ongoing education through the employee’s life-cycle led by Summit University.

The employee education process begins during orientation where all new employees receive a comprehensive overview of the Company, partnership, and the molecule’s mechanism of action.

This educational program also includes oncology training, anatomy, physiology, disease state awareness, testing, and symptoms along with the patient journey as it pertains to the Summit clinical trials.

This strategy helps to ensure scientists as well as administrators start their employment with a strong foundation of shared knowledge to power the Company and its culture.

Workplace Health and Safety

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

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

We have again had no reportable health and safety issues in 2023.

We accomplish this through the 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 2024.

Our Corporate Information

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Our website is https://www.smmttx.com.

The information contained on, or that can be accessed through, our website is not incorporated by reference into this Report or in any other report or document we file with the SEC, and any reference to our website address is intended to be an inactive textual reference only.

The information contained on, or that can be accessed through, our website is not incorporated by reference into this Annual Report on Form 10-K or in any other report or document we file with the SEC, and any reference to our website address is intended to be an inactive textual reference only.

We own or have rights to trademarks, service marks, and trade names that we use in connection with the operation of our business, including our corporate name, logos and website names.

Other trademarks, service marks, and trade names appearing in this Report are the property of their respective owners.

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

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.

Available Information

We maintain a website with the address https://www.smmttx.com/.

We are not including the information contained on our website as part of, or incorporating it by reference into, this 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 Securities and Exchange Commission (“SEC”).

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.

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