What changed in this filing

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Item 1. Business

2024-02-22 compared with 2023-02-23 · 284 added, 270 removed, 576 unchanged (49% of the section changed)

With more than 65 years of experience in delivering life-changing science, Lantheus is committed to improving patient outcomes through diagnostics, radiotherapeutics and artificial intelligence solutions that enable clinicians to Find, Fight and Follow disease.

We are the leading radiopharmaceutical-focused company, delivering life-changing science to enable clinicians to Find, Fight and Follow disease to deliver better patient outcomes.

We classify our products in three categories:

Precision Diagnostics, Radiopharmaceutical Oncology, and Strategic Partnerships and Other Revenue.

Our leading Precision Diagnostic products assist healthcare professionals (“HCPs”) Find and Follow diseases, with a focus in cardiology.

Our Radiopharmaceutical Oncology diagnostics and therapeutics help HCPs Find, Fight and Follow cancer.

Our Strategic Partnerships focus on enabling precision medicine through the use of biomarkers, digital solutions and pharma services platforms, and also includes our license of RELISTOR to Bausch Health Companies, Inc.

Our commercial products are used by oncologists, urologists, nuclear medicine physicians, cardiologists, sonographers, technologists, radiologists, and internal medicine physicians working in a variety of clinical settings.

Radiopharmaceutical Oncology, Precision Diagnostics, and Strategic Partnerships and Other Revenue.

Our Radiopharmaceutical Oncology diagnostics and therapeutic candidates help healthcare professionals (“HCPs”) Find, Fight and Follow cancer, with a focus in prostate cancer.

Our leading Precision Diagnostic products assist HCPs to Find and Follow diseases, with a focus in cardiology.

Our Strategic Partnerships focus on enabling precision medicine through the use of biomarkers, digital solutions and pharma solutions platforms.

Our commercial products are used by cardiologists, internal medicine physicians, nuclear medicine physicians, oncologists, radiologists, sonographers, technologists, and urologists working in a variety of clinical settings.

We believe that our diagnostic products provide improved diagnostic information that enables HCPs to better detect and characterize, or rule out, disease, with the potential to achieve better patient outcomes, reduce patient risk and limit overall costs throughout the healthcare system.

We produce and market our products throughout the United States (the “United States” or the “U.S.”), selling primarily to hospitals, independent diagnostic testing facilities, government facilities, integrated delivery networks, radiopharmacies, clinics, and group practices.

We sell our products outside the U.S.

through a combination of direct distribution in Canada and third party distribution relationships in Europe, Canada, Australia, Asia-Pacific, Central America and South America.

Our executive offices are located in Bedford, MA, with additional offices in North Billerica, MA, Somerset, NJ, Montreal, Canada and Lund, Sweden.

Our executive offices are located in Bedford, Massachusetts, with additional offices in North Billerica, Massachusetts;

Somerset, New Jersey (subject to the satisfaction of closing conditions for the sale of the Somerset facility and related assets to Perspective anticipated in the first half of 2024);

Montreal, Canada and Lund, Sweden.

CEO Succession Plan

On January 23, 2024, we announced that, effective March 1, 2024, Brian Markison, our current Chair of the Board of Directors (“Board”), will become our Chief Executive Officer, and Mary Anne Heino, our current Chief Executive Officer, will retire and become the Chair of the Board.

As part of this leadership transition, Mr.

Markison assumed the role of Executive Chair of the Board as of January 23, 2024 until the effectiveness of his Chief Executive Officer appointment in March, and Board Member Julie McHugh became Lead Independent Director.

Strategic Agreements with Perspective Therapeutics

On January 9, 2024, we announced that we entered into multiple strategic agreements with Perspective, a radiopharmaceutical company that is pursuing advanced treatment applications for cancers throughout the body.

Under the agreements, we obtained an option to exclusively license Perspective’s Pb212-VMT- ⍺-NET, a clinical stage alpha therapy in development for the treatment of neuroendocrine tumors, and an option to co-develop certain early-stage therapeutic candidates targeting prostate cancer using Perspective’s innovative platform technology for an aggregate upfront payment of $28 million in cash.

We also agreed to purchase up to 19.9% of Perspective’s outstanding shares of common stock for up to approximately $33 million, subject to Perspective’s completion of a qualified third-party financing transaction and certain other closing conditions.

In addition, Perspective agreed to acquire the assets and associated lease of our radiopharmaceutical manufacturing facility in Somerset, New Jersey.

Following satisfaction of the closing conditions, on January 22, 2024, our subsidiary, Lantheus Alpha purchased 56,342,355 shares of Perspective’s common stock at a purchase price of $0.37 per share in a private placement transaction.

The total consideration for the purchase was approximately $20.8 million in cash, which resulted in Lantheus Alpha holding approximately 10.74% of Perspective’s common stock as of the purchase date and retaining the right to purchase additional shares to bring its ownership up to an aggregate of 19.9%.

Exclusive License for PNT2002 & PNT2003

On December 20, 2022, we announced the closing of a set of strategic collaborations with an affiliate of POINT, in which we were granted a license to exclusive worldwide rights (excluding Japan, South Korea, China (including Hong Kong, Macau and Taiwan), Singapore and Indonesia) to co-develop and commercialize POINT’s PNT2002 and PNT2003 product candidates.

PNT2002 is a prostate-specific membrane antigen-targeted radiopharmaceutical therapy for the treatment of metastatic castrate-resistant prostate cancer.

PNT2003 is a somatostatin receptor targeted radioligand (“SSTR”) therapy with non-carrier added lutetium-177, and is in development to treat patients with SSTR-positive neuroendocrine tumors.

In exchange for these rights, we paid $260.0 million in upfront payments between the two agreements with POINT, with the potential for additional milestone payments of approximately $1.8 billion between the two products based on FDA approval, net sales and commercial milestones.

Additionally, we will pay POINT royalties on net sales, beyond certain financial thresholds and subject to conditions, of 20% for PNT2002 and 15% for PNT2003.

The license agreements expand our radiopharmaceutical portfolio with two late-stage therapeutic candidates and, with PNT2002, broadens our prostate cancer franchise.

For more information, see Note 22, “Acquisition of Assets”, in our consolidated financial statements included herein.

On December 20, 2022, we announced the closing of a set of strategic collaborations with POINT, in which we were granted a license to exclusive worldwide rights (excluding Japan, South Korea, China (including Hong Kong, Macau and Taiwan), Singapore and Indonesia) to co-develop and commercialize POINT’s PNT2002 and PNT2003 product candidates.

PNT2002 is a PSMA-targeted radiopharmaceutical therapy in development for the treatment of metastatic castration-resistant prostate cancer (“mCRPC”).

PNT2003 is a somatostatin receptor (“SSTR”) therapy with non-carrier added lutetium-177, which is in registration to treat patients with SSTR-positive neuroendocrine tumors.

On December 27, 2023, Eli Lilly and Company announced the completion of its acquisition of POINT.

The acquisition is not expected to impact the status of the license agreements related to these product candidates or the work being performed in connection with those license agreements and our collaboration with POINT.

With respect to PNT2002, POINT is generally responsible for funding and development activities required for FDA approval, including generating all clinical and nonclinical data, analysis and other information, and we are responsible for preparing for and seeking regulatory approval, as well as performing and funding all future development and commercialization following such approval.

POINT will be responsible for all manufacturing of PNT2002, subject to certain exceptions described in the license and collaboration agreement between Lantheus Two and POINT, dated November 11, 2022 (the “PNT2002 License Agreement”).

In April 2023, we announced with POINT that the FDA had granted Fast Track designation for PNT2002.

Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and address unmet needs.

On December 18, 2023, we announced positive topline results from SPLASH.

SPLASH is designed to evaluate the efficacy and safety of PNT2002 in patients with mCRPC who have progressed following treatment with an androgen receptor pathway inhibitor (“ARPI”).

The SPLASH trial met its primary endpoint, demonstrating a median radiographic progression-free survival (rPFS) per blinded independent central review of 9.5 months for patients treated with PNT2002, compared to 6.0 months for patients treated with ARPI in the control arm, a statistically significant 29% reduction in the risk of radiographic progression or death (hazard ratio (“HR”) 0.71;

At the time of the analysis, interim overall survival (“OS”) results were immature (46% of protocol-specified target OS events reached), and the HR was 1.11.

We expect more mature overall survival data in 2024 prior to the potential submission of a New Drug Application (“NDA”).

PNT2002 demonstrated a favorable safety profile with grade ≥3 treatment-emergent adverse events (“TEAEs”) per Common Terminology Criteria for Adverse Events, serious TEAEs, and TEAEs leading to discontinuation occurring at lower rates in the PNT2002 arm than in the ARPI arm (30.1%, 17.1%, and 1.9% versus 36.9%, 23.1%, and 6.2%, respectively).

The open-label study randomized 412 patients with PSMA-expressing mCRPC who had progressed on ARPI therapy and either refused or were not eligible for chemotherapy, in a 2:1 randomization ratio.

At the time of the analysis, 84.6% of patients who experienced progressive disease in the control arm subsequently crossed over to receive PNT2002.

SPLASH was conducted across the United States, Canada, Europe, and the United Kingdom.

Eighty percent of SPLASH patients resided in North America and approximately ten percent of all participants were Black or African American.

During 2023, we worked on establishing an Expanded Access Program, (“EAP”), for PNT2002.

EAPs, which are also referred to as compassionate use programs, provide a potential pathway for patients with serious or life-threatening conditions to gain access to an investigational drug for treatment outside of a clinical trial.

We expect to enroll the first patient in the EAP for PNT2002 during the first quarter of 2024.

With respect to PNT2003, POINT is responsible for curating all data, analysis and other information necessary for regulatory approval, and supporting us in the preparation of regulatory filings.

We are responsible for preparing for and seeking regulatory approval of all such applications, as well as performing and funding all future development and commercialization of PNT2003 following such approval.

POINT will be responsible for all manufacturing of PNT2003, subject to certain exceptions described in the license and collaboration agreement between Lantheus Three and POINT, dated November 11, 2022 (the “PNT2003 License Agreement”).

On January 11, 2024, we announced that our ANDA for Lutetium Lu 177 Dotatate (177Lu-PNT2003) had been accepted for filing by the FDA.

On January 26, 2024, we were sued in the District Court for the District of Delaware by Advanced Accelerator Applications USA, Inc.

and Advanced Accelerator Applications SA, each a Novartis entity, for patent infringement in response to the Company’s ANDA filing.

Based on the most recent update to the FDA’s online paragraph IV database listings, we believe we are the first applicant to have filed a substantially complete ANDA for Lutetium Lu 177 Dotatate containing a Paragraph IV certification under the provisions of the Hatch-Waxman Act.

As the first applicant, we believe we will be eligible for 180 days of generic marketing exclusivity in the U.S.

Under the Hatch-Waxman Act, any company submitting an ANDA must make certain certifications with respect to the patent status of the drug for which it is seeking approval.

In the event that such applicant plans to challenge the validity or enforceability of an existing listed patent or asserts that the proposed product does not infringe an existing listed patent, it files a “Paragraph IV” certification.

We filed a Paragraph IV certification in connection with PNT2003.

In the case of ANDAs, the Hatch-Waxman Act provides for a potential 180-day period of generic exclusivity for the first company to submit an ANDA with a Paragraph IV certification.

This filing triggers a regulatory process in which the FDA is required to delay the final approval of subsequently filed ANDAs containing Paragraph IV certifications until 180 days after the first commercial marketing.

When litigation is brought by the

patent holder in response to a Paragraph IV certification (like the Novartis entities did for our ANDA for PNT2003), the FDA generally may not approve the ANDA until the earlier of 30 months or a court decision finding the patent invalid, not infringed or unenforceable.

The submission of our ANDA for PNT2003 could result in protracted and expensive patent litigation and the outcome of such litigation is uncertain.

Acquisition of Cerveau

On February 6, 2023, we announced that we acquired Cerveau.

Cerveau holds the rights under a license agreement to develop and commercialize MK-6240, an investigational second-generation F 18-labeled PET imaging agent that targets Tau tangles in Alzheimer’s disease.

Under the terms of our purchase agreement, we paid the stockholders of Cerveau (the “Selling Stockholders”) an upfront payment of $35.0 million in February 2023 and an additional $10.0 million in May 2023 upon the successful completion of a technology transfer.

The Selling Stockholders are also eligible to receive additional development and commercial milestone payments.

Additionally, we will pay double-digit royalty payments for research revenue and commercial sales.

Research revenue is derived from existing partnerships with pharmaceutical companies that use MK-6240 in clinical trials and includes milestone and dose-related payments.

Pursuant to the terms of the stock purchase agreement for Cerveau, certain members of the Selling Stockholders will also provide transition and clinical development services for a prescribed time following the closing of the transaction.

Our Portfolio of Commercial Products

Radiopharmaceutical Oncology

Our commercial product in our Radiopharmaceutical Oncology category includes the following:

• PYLARIFY (also known as piflufolastat F 18, 18F-DCFPyL or PyL) is an F 18-labelled PSMA-targeted PET imaging agent used with PET/computed tomography (“CT”).

PYLARIFY is indicated in the U.S.

for PET imaging of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy and in men with suspected recurrence based on elevated serum prostate-specific antigen (“PSA”) levels.

Piflufolastat F 18 is approved under the name PYLCLARI in Europe and licensed by us to Curium.

Precision Diagnostics

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• DEFINITY is an injectable ultrasound enhancing agent with perflutren-containing lipid microspheres, or microbubbles, that is used in echocardiography exams.

One formulation of DEFINITY requires refrigerated storage.

Another formulation, which we have branded as DEFINITY RT, allows both storage and shipment at room temperature and provides clinicians an additional choice for greater utility of this formulation in broader clinical settings.

We offer two formulations of DEFINITY, one of which requires refrigerated storage (branded DEFINITY) and one which allows both storage and shipment at room temperature and provides clinicians an additional choice for greater utility of this formulation in broader clinical settings (branded DEFINITY RT).

The indication for both formulations in the U.S.

is for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border.

We believe we are currently the leading worldwide provider of ultrasound enhancing agents.

We believe we are currently the leading worldwide provider of ultrasound enhancing agents for use in echocardiography.

• TechneLite is a Technetium (“Tc-99m”) generator that provides the essential nuclear material used by radiopharmacies to radiolabel NEUROLITE, CARDIOLITE and other Tc-99m-based radiopharmaceuticals used in nuclear medicine procedures.

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• NEUROLITE is an injectable, Tc-99m-labeled imaging agent used with single-photon emission computed tomography (“SPECT”) technology to identify the area within the brain where blood flow has been blocked or reduced due to stroke.

Although NEUROLITE’s patents and market exclusivity have expired, we are not currently aware of any generic competitors.

• Xenon-133 (“Xenon”) is a radiopharmaceutical gas that is inhaled and used to assess pulmonary function and also to image cerebral blood flow.

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• CARDIOLITE, also known by its generic name sestamibi, is an injectable, Tc-99m-labeled imaging agent used in myocardial perfusion imaging (“MPI”) procedures to assess blood flow to the muscle of the heart using SPECT.

CARDIOLITE was approved by the FDA in 1990 and its market exclusivity expired in July 2008.

Included in CARDIOLITE revenues are branded CARDIOLITE and generic sestamibi revenues.

Radiopharmaceutical Oncology

Our commercial products in our Radiopharmaceutical Oncology category include the following:

• PYLARIFY (also known as piflufolastat F 18, 18F-DCFPyL or PyL) is an F 18-labelled PSMA-targeted PET imaging agent used with PET/computed tomography (“CT”).

PYLARIFY is indicated in the U.S.

• AZEDRA (iobenguane I 131) is a radiotherapeutic, approved for the treatment of patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.

AZEDRA is the first and only FDA-approved therapy for this indication.

Strategic Partnerships and Other Revenue

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a subcutaneous injection and an oral tablet.

We have licensed RELISTOR to Bausch, and we collect quarterly royalties based on RELISTOR sales.

In 2011 Progenics licensed methylnaltrexone (MNTX) along with products containing MNTX, including both approved forms of RELISTOR, to Salix Pharmaceuticals, Inc., a Bausch Health company (“Bausch”) and on August 2, 2023, we sold the right to the RELISTOR net sales royalties under that license agreement and retained the rights to future sales-based milestone payments.

• Automated Bone Scan Index (“aBSI”) automatically calculates the disease burden of prostate cancer by detecting and classifying bone scan tracer uptakes as metastatic or benign lesions using an artificial neural network.

aBSI is FDA cleared and CE marked.

The software is currently used as one of the correlative objectives of the DORA trial, an open-labeled, randomized, phase III study of docetaxel versus docetaxel in combination with radium-223 (Ra-223) in subjects with mCRPC.

The software is currently used as one of the correlative objectives of the DORA trial, an open-labeled, randomized, Phase 3 study of docetaxel versus docetaxel in combination with radium-223 (Ra-223) in subjects with mCRPC.

aBSI is also approved in Japan and part of the JSMO guidelines (Japanese Society of Medical Oncology) in support of clinicians with patient treatment selection.

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(“FUJIFILM”) under the name BONENAVI®.

• aPROMISE, which is currently sold as PYLARIFY AI in the U.S., is artificial intelligence medical device software that is designed to allow healthcare professionals and researchers to perform standardized quantitative assessment of PSMA PET/CT images in prostate cancer, including those images obtained by using PYLARIFY.

• aPROMISE, which is currently commercialized as PYLARIFY AI in the U.S., is artificial intelligence medical device software that is designed to allow HCPs and researchers to perform standardized quantitative assessment of PSMA PET/CT images in prostate cancer, including those images obtained by using PYLARIFY.

Additional Information about our Product Categories

Radiopharmaceutical Oncology

Continued Growth of PYLARIFY

PYLARIFY is the leading radiopharmaceutical diagnostic agent indicated for PET imaging of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy and in men with suspected recurrence based on elevated PSA levels.

PYLARIFY works by binding to PSMA, a protein that is overexpressed on the surface of more than 90% of primary and metastatic prostate cancer cells.

PYLARIFY works with PET/CT technology to produce a combined scan that enables the scan reader to detect and locate the disease.

According to the American Cancer Society, prostate cancer is the second most common cancer in American men - one in eight American men will be diagnosed with prostate cancer in their lifetimes and over 3.3 million American men are living with prostate cancer today.

Based on estimates from third-party sources regarding the incidence of prostate cancer in men in the U.S., we believe the current market potential for PSMA PET imaging agents in the U.S.

for 2024 could be about 445,000 scans, and the total addressable market by 2029 could be over 700,000 annual scans.

PYLARIFY is manufactured on a diverse, F 18 distributor supply network of PMFs, ensuring convenient and reliable supply.

After being made on a cyclotron at a PMF, the F 18 is then combined with certain chemical ingredients in specially designed chemistry synthesis boxes to manufacture PYLARIFY.

The finished PYLARIFY is then quality control tested and transferred to a radiopharmacist who prepares and dispenses patient-specific doses of the final product.

Because each PMF manufacturing PYLARIFY is deemed by the FDA to be a separate manufacturing site, each is separately approved by the FDA.

As of December 31, 2023, we had activated 54 PMF manufacturing sites in our PMF network, up from 37 activated sites as of December 31, 2022.

These additional sites provide geographic breadth, out-the-door time flexibility and added optionality within our existing PMF network.

Overall, we have achieved broad national distribution of PYLARIFY with customers in 47 of 50 states, the District of Columbia and Puerto Rico.

In addition to our network of commercial PMFs, we also work with academic medical centers in the U.S.

that have radioisotope-producing cyclotrons and that have expressed an interest in manufacturing PYLARIFY.

For this initiative, we enter into a fee-for-service arrangement under which the academic medical center manufactures F 18 on its cyclotron and completes the manufacturing process for PYLARIFY.

PYLARIFY can then be used by the academic medical center itself, and in some cases distributed to other customers under separate purchase agreements.

Our Healthcare Procedure Coding System (“HCPCS”) code, which enables streamlined billing, went into effect as of January 1, 2022.

In addition, effective January 1, 2022, the Centers for Medicare and Medicaid Services (“CMS”) granted TPT Status in the hospital outpatient setting for PYLARIFY, enabling traditional Medicare to provide an incremental payment for PET/CT scans performed with PYLARIFY in that setting.

TPT Status for PYLARIFY is expected to expire on December 31, 2024.

In July 2023, CMS proposed possible changes to its regulations covering payment for diagnostic radiopharmaceuticals.

This included, for the first time since 2008, options for separate payment for diagnostics instead of the current packaged payment following expiration of TPT Status.

We, along with numerous industry organizations, submitted comments to CMS.

In completing its 2023 rulemaking for the 2024 payment calendar year, CMS recognized the challenges of patient access to diagnostic radiopharmaceuticals and requested feedback on various payment alternatives that could provide separate reimbursement for these items, but the agency did not adopt any of these proposals in the final rule, while stating that it would continue to evaluate this issue in subsequent rulemaking.

We plan to submit additional comments to CMS in connection with its 2024 rulemaking for the 2025 payment calendar year.

Our continued growth of PYLARIFY will depend on our ability to clinically and commercially differentiate PYLARIFY from other products on the market and to maintain PYLARIFY as the leading PSMA PET imaging agent in a competitive marketplace.

PYLARIFY’s current competition is primarily two Gallium-68 (“Ga-68”)-based PSMA imaging agents, a fluorine-18-based PSMA

imaging agent, and other non-PSMA-based imaging agents commonly referred to as conventional imaging.

Continued growth and revenue contribution from PYLARIFY will also depend on our ability to differentiate PYLARIFY in light of the potential loss of TPT Status, including through flexible and dependable access to PYLARIFY nationally, a best in class customer experience and through long-term strategic contracts.

We actively pursue patents in connection with PYLARIFY, both in the U.S.

and internationally.

for PYLARIFY, we have five Orange Book-listed patents, including composition of matter patents, the last of which expires in 2037.

Outside of the U.S., we have, and are currently pursuing, additional PYLARIFY patents to obtain similar patent protection as in the U.S.

See Part I, Item 1A.

“Risk Factors” for information regarding certain risks associated with PYLARIFY and Part II, Item 7.

“Management’s Discussion and Analysis of Financial Condition and Results of Operations - Comparison of the Periods Ended December 31, 2023 and 2022 - Revenues” for further information on total revenue contributed by PYLARIFY since its approval.

Precision Diagnostics

Continued Growth of DEFINITY

DEFINITY is the leading ultrasound enhancing agent based on revenue in the U.S., and is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border.

DEFINITY is the leading ultrasound enhancing agent in the U.S.

and is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border.

Numerous patient conditions can decrease the quality of images of the left ventricle, the primary pumping chamber of the heart.

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one that requires refrigerated storage and one that we have branded as DEFINITY RT that may be stored at room temperature.

DEFINITY is a clear, colorless, sterile liquid that, upon activation in a VIALMIX apparatus, a medical device specifically designed for DEFINITY, becomes a homogenous, opaque, milky white injectable suspension of perflutren-containing lipid microspheres.

DEFINITY is a clear, colorless, sterile liquid that, upon activation in a VIALMIX or VIALMIX RFID, medical devices specifically designed for DEFINITY, becomes a homogenous, opaque, milky white injectable suspension of perflutren-containing lipid microspheres.

After activation and intravenous injection, DEFINITY opacifies the left ventricular chamber and improves the delineation of the left ventricular endocardial border, or innermost layer of tissue that lines the chamber of the left ventricle.

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Based on estimates from third party sources, we believe there were approximately 29 to 30 million echocardiograms performed in the U.S.

in 2021 (the latest time period for which full year data is available and which also included the estimated impacts of COVID-19 and staffing challenges on procedure volumes).

in 2022 (the latest time period for which full year data is available).

Assuming that between 20% and 30% of echocardiograms produce suboptimal images, as stated in the clinical literature, we estimate that approximately 6 to 9 million echocardiograms in 2022 produced suboptimal images.

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segment for ultrasound enhancing agents in echocardiography procedures.

DEFINITY currently competes with ultrasound enhancing agents produced by GE Healthcare and Bracco Diagnostics Inc.

(“Bracco”), as well as echocardiography without the use of ultrasound enhancing agents and non-echocardiography imaging modalities.

DEFINITY and the agents produced by GE Healthcare and Bracco all carry an FDA-required boxed warning, which has been modified over time, to notify physicians and patients about potentially serious safety concerns or risks posed by the products.

DEFINITY currently competes with two other FDA-approved ultrasound enhancing agents, as well as echocardiography without the use of ultrasound enhancing agents and non-echocardiography imaging modalities.

DEFINITY and the other FDA-approved ultrasound enhancing agents all carry an FDA-required boxed warning, which has been modified over time, to notify physicians and patients about potentially serious safety concerns or risks posed by the products.

See Part I, Item 1A.

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and internationally.

for DEFINITY, we have six Orange Book-listed method of use patents, one of which expires in 2035 and five of which expire in 2037, as well as additional manufacturing patents that are not Orange Book-listed expiring in 2023 and 2037.

for DEFINITY, we have six Orange Book-listed method-of-use patents, one of which expires in 2035 and five of which expire in 2037, as well as additional manufacturing patents that are not Orange Book-listed expiring in 2037.

for DEFINITY RT, we have eight Orange Book-listed patents, including two composition of matter patents which expire in 2035.

Outside of the U.S., we are currently pursuing additional DEFINITY and DEFINITY RT patents to obtain similar patent protection as in the U.S.

The Orange Book-listed patents include a patent on the use of VIALMIX RFID (see below), which expires in 2037;

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The RFID tag, which is affixed to the vial label, enables the DEFINITY vial to be appropriately activated with the VIALMIX RFID activation device.

With respect to manufacturing the formulation of DEFINITY that requires refrigeration, historically, we have relied on Jubilant HollisterStier (“JHS”) as a significant supplier of this formulation of DEFINITY.

We constructed a specialized in-house manufacturing facility at our North Billerica campus for purposes of producing this formulation of DEFINITY and, potentially, other sterile vial products.

To manufacture DEFINITY that requires refrigeration, historically, we have relied on Jubilant HollisterStier (“JHS”) as a significant supplier.

We constructed a specialized in-house manufacturing facility at our North Billerica campus for purposes of

producing this formulation of DEFINITY and, potentially, other sterile vial products.

On February 22, 2022, we received FDA approval of our supplemental new drug application (“sNDA”), authorizing commercial manufacturing of this formulation of DEFINITY at our new facility.

We believe this investment allows us to better manage DEFINITY manufacturing for this formulation and inventory, reduce our costs in a potentially more price competitive environment, and provide us with supply chain redundancy.

We believe this investment provides supply chain redundancy, improved flexibility and reduced costs in a potentially more price competitive environment.

See Part I, Item 1A.

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Tc-99m results from the radioactive decay of Mo-99, itself a radioisotope with a 66-hour half-life sourced in our supply chain in nuclear research reactors located in Belgium, South Africa and Australia from enriched uranium.

The TechneLite generator is slightly larger than a coffee can in size, and the self-contained system houses a vertical glass column at its core that contains Mo-99, which degrades to Tc-99m.

The TechneLite generator is a self-contained system that houses a vertical glass column at its core that contains Mo-99, which degrades to Tc-99m.

During our manufacturing process, Mo-99 is added to the column within the generator where it is adsorbed onto alumina powder.

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TechneLite is currently marketed primarily in the U.S., Canada, Central America and South America, largely to radiopharmacies that prepare unit doses of radiopharmaceutical imaging agents and ship these preparations directly to hospitals for administration to patients.

In the U.S., we have supply contracts with large radiopharmacy groups, including Cardinal Health (“Cardinal”), RLS (USA) Inc.

(previously GE Healthcare) (“RLS”), United Pharmacy Partners (“UPPI”) and PharmaLogic Holdings Corp (“PharmaLogic”).

In the U.S., we have supply contracts with large radiopharmacy groups, including PharmaLogic Holdings Corp (“PharmaLogic”), Cardinal Health (“Cardinal”), RLS (USA) Inc.

(previously GE Healthcare) (“RLS”) and United Pharmacy Partners (“UPPI”).

We also supply generators on a purchase order basis to other customers.

We estimate that TechneLite had approximately one third of the U.S.

generator market as of December 31, 2022, competing primarily with Tc-99m-based generators produced by Curium and NorthStar Medical Radioisotopes, LLC (“Northstar”).

Outside of the U.S., we sell generators through supply agreements with radiopharmacy chains, through distributors or to separate customers.

The Mo-99 used in our TechneLite generators can be produced using targets made of either highly-enriched uranium (“HEU”) or low-enriched uranium (“LEU”).

LEU consists of uranium that contains less than 20% of the uranium-235 isotope.

HEU is considered weapons grade material, with 20% or more of uranium-235.

The American Medical Isotopes Production Act of 2012 encourages the domestic production of LEU Mo-99 and provides for the eventual prohibition of the export of HEU from the U.S.

Although Medicare generally does not provide separate payment to hospitals for the use of diagnostic radiopharmaceuticals administered in an outpatient setting, since 2013, the Centers for Medicare and Medicaid Services (“CMS”), the federal agency responsible for administering the Medicare program, has provided an add-on payment of $10 under the hospital outpatient prospective payment system for every Tc-99m diagnostic dose produced from non-HEU sourced Mo-99, to cover the marginal cost for radioisotopes produced from non-HEU sources.

Our LEU TechneLite generator satisfies the reimbursement requirements under the applicable CMS rules.

We believe that our substantial capital investments in our highly automated TechneLite production line and our extensive experience in complying with the stringent regulatory requirements for the handling of nuclear materials, create significant and sustainable competitive advantages for us in generator manufacturing and distribution.

generator market as of December 31, 2023, competing primarily with Tc-99m-based generators produced by Curium.

We believe that our substantial capital investments in our TechneLite production line and our extensive experience in complying with the stringent regulatory requirements for the handling of nuclear materials, create significant and sustainable competitive advantages for us in generator manufacturing and distribution.

Given our significant know-how and trade secrets associated with the methods of manufacturing and assembling the TechneLite generator, we believe we have a substantial amount of valuable and defensible proprietary intellectual property associated with the product.

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Radiopharmaceutical Oncology

Continued Growth of PYLARIFY

PYLARIFY is a radioactive diagnostic agent indicated for PET imaging of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy and in men with suspected recurrence based on elevated PSA levels.

PYLARIFY works by binding to PSMA, a protein that is overexpressed on the surface of more than 90% of primary and metastatic prostate cancer cells.

PYLARIFY works with PET/CT technology to produce a combined PET/CT scan that enables the reader of the PET/CT scan to detect and locate the disease.

According to the American Cancer Society, prostate cancer is the second most common cancer in American men - one in eight American men will be diagnosed with prostate cancer in their lifetimes and over 3.2 million American men are living with prostate cancer today.

Based on estimates from third party sources regarding the incidence of prostate cancer in men in the U.S., we believe the market potential for PSMA PET imaging agents in the U.S.

could be up to 350,000 annual scans, comprised of 125,000 scans for patients with intermediate, unfavorable or high/very high risk of suspected metastases of prostate cancer, 195,000 scans for patients with suspected recurrence of prostate cancer, and 30,000 scans for patients with metastatic castration-resistant prostate cancer (“mCRPC”) who may be under consideration for PSMA-targeted therapy for the treatment of adult patients with PSMA-positive mCRPC who have already been treated with other anticancer treatments (androgen receptor pathway inhibition and taxane-based chemotherapy).

In March 2022, we announced a strategic collaboration with Novartis to include PYLARIFY in prostate cancer trials with PLUVICTO, Novartis’ PSMA-targeted therapeutic.

In addition, in 2022, we entered into an agreement with Curium to add PYLARIFY to its PSMA-targeted therapeutic clinical trial referred to by Curium as ECLIPSE.

Both of these collaborations, as well as other collaborations using PYLARIFY, are described further under Strategic Partnerships and Other Revenue – Oncology below.

Also, during 2022, the National Comprehensive Cancer Center updated its guidelines and the Society for Nuclear Medicine and Molecular Imaging updated its appropriate use criteria, both noting that PSMA PET imaging agents, including PYLARIFY, can be used for patient selection for PSMA-targeted radioligand therapy.

The commercial launch of PYLARIFY was complex and, we believe, highly successful.

To manufacture PYLARIFY, we assembled and qualified a nationwide network of PMFs with cyclotrons that produce F 18.

After being made on a cyclotron at a PMF, the F 18 is then combined with certain chemical ingredients in specially designed chemistry synthesis boxes to manufacture PYLARIFY.

The finished PYLARIFY is then quality control tested and transferred to a radiopharmacist who prepares and dispenses patient-specific doses of the final product.

Because each of the PMFs manufacturing these products is deemed by the FDA to be a separate manufacturing site, each had to be separately approved by the FDA.

As of December 31, 2022, we had activated 37 PMF manufacturing sites in our PMF network, up from 21 activated sites as of December 31, 2021.

These additional sites provide geographic breadth, out-the-door time flexibility and added optionality within our existing PMF network.

Overall, we have achieved broad national distribution of PYLARIFY with customers in 46 of 50 states, including the District of Columbia.

In addition to our network of PMFs, we have also been working with academic medical centers in the U.S.

that have radioisotope-producing cyclotrons who have expressed an interest in manufacturing PYLARIFY.

For this initiative, we enter into a fee-for-service arrangement under which the academic medical center manufactures F 18 on its cyclotron and completes the manufacturing process for PYLARIFY.

PYLARIFY can then be used by the academic medical center itself, and in some cases distributed to other customers under separate purchase agreements.

Our commercial launch also required obtaining adequate coding, coverage and payment for PYLARIFY, including not only coverage from Medicare, Medicaid and other government payors, as well as private payors, but also appropriate payment levels to adequately cover our customers’ costs of using PYLARIFY in PSMA PET/CT imaging procedures.

The Healthcare Procedure Coding System (“HCPCS”) code, which enables streamlined billing went into effect as of January 1, 2022.

In addition, effective January 1, 2022, CMS granted Transitional Pass-Through Payment Status (“TPT Status”) under the Hospital Outpatient Prospect Payment System (“OPPS”) for PYLARIFY, enabling CMS to provide separate payment for PET/CT scans performed with PYLARIFY.

Note that TPT only applies to traditional fee-for-service Medicare in the hospital outpatient setting.

TPT Status for PYLARIFY is expected to expire December 31, 2024.

After TPT Status expires, under current Medicare rules, PYLARIFY, similar to other diagnostic radiopharmaceuticals, would not be separately reimbursed in the hospital outpatient setting, but rather would be bundled into the facility payment a hospital receives for a PET/CT imaging procedure, and the facility payment may not always adequately cover the total cost of the procedure.

Our successful growth of PYLARIFY will depend on our ability to maintain PYLARIFY as the leading PSMA PET imaging agent in a competitive environment in which other PSMA PET imaging agents have been approved and additional ones are in development.

PYLARIFY’s current competition is primarily two commercially available Gallium-68 (“Ga-68”)-based PSMA imaging agents, as well as other non-PSMA-based imaging agents.

We may also face competition from an F 18 PSMA PET imaging agent currently under review by the FDA.

We actively pursue patents in connection with PYLARIFY, both in the U.S.

and internationally.

for PYLARIFY, we have four Orange Book-listed patents, including composition of matter patents, the last of which expires in 2037.

Outside of the U.S., we have, and are currently pursuing, additional PYLARIFY patents to obtain similar patent protection as in the U.S.

See Part I, Item 1A.

“Risk Factors” for information regarding certain risks associated with PYLARIFY and Part II, Item 7.

“Management’s Discussion and Analysis of Financial Condition and Results of Operations - Comparison of the Periods Ended December 31, 2022 and 2021 - Revenues” for further information on total revenue contributed by PYLARIFY since its approval.

Strategic Partnerships and Other Revenue

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We are evaluating a number of different opportunities to collaborate, in-license or acquire additional products, product candidates, businesses and technologies to drive our future growth.

In particular, we are focused on late-stage diagnostic and therapeutic product opportunities in oncology and other strategic areas that complement our existing portfolio.

Our Pharma Services business focuses on advancing innovative imaging biomarker solutions through collaborations with pharmaceutical companies and academic centers.

In particular, we are focused on radiopharmaceutical therapeutic and diagnostic product opportunities in oncology and other strategic areas that complement our existing portfolio.

Our Pharma Solutions business focuses on advancing innovative imaging biomarker solutions, such as MK-6240, through collaborations with pharmaceutical companies and academic centers.

Our Digital Solutions business focuses on developing and commercializing 510(k) cleared and CE marked digital applications to enhance the performance of imaging agents;

our Digital Solutions portfolio currently includes aBSI, aPROMISE and PYLARIFY AI.

As we continue to pursue expanding strategic partnerships, our Pharma Services activities in oncology include:

As we continue to pursue expanding strategic partnerships, our Pharma Solutions activities in oncology include:

• Prostate Cancer – We collaborate with pharmaceutical companies developing therapies and diagnostics in prostate cancer.

▪ In June 2022, Curium (our licensee that is developing and commercializing piflufolastat F 18 in Europe) announced that it had submitted its marketing authorization application to the European Medicines Agency seeking approval for piflufolastat F 18.

In addition, in 2022, we entered into an agreement with Curium to add PYLARIFY to its U.S.

ECLIPSE trial, a multi-center, open-label, randomized Phase 3 trial comparing the safety and efficacy of Curium’s PSMA-targeted therapeutic versus hormone therapy in patients with metastatic castration-resistant prostate cancer.

▪ In July 2023, Curium (our licensee that is developing and commercializing piflufolastat F 18 in Europe) announced that it received marketing authorization for piflufolastat F 18, under the name PYLCLARI, from the European Commission.

In addition, we previously entered into an agreement with Curium to add PYLARIFY to its U.S.

ECLIPSE trial, a multi-center, open-label, randomized Phase 3 trial comparing the safety and efficacy of Curium’s PSMA-targeted therapeutic versus hormone therapy in patients mCRPC.

PYLARIFY will be used to determine PSMA-avidity as part of patient selection.

▪ In March 2022, we announced a collaboration with Novartis to include PYLARIFY in prostate cancer trials with PLUVICTO.

As part of the agreement with Novartis, we will provide PYLARIFY for the selection of patients with prostate cancer for the trials, and Novartis will provide all PYLARIFY-related clinical imaging data to us.

▪ In January 2022, we announced a collaboration with the Prostate Cancer Clinical Trial Consortium (“PCCTC”), a premier multicenter clinical research organization that specializes in prostate cancer research.

The intent of the strategic collaboration is to integrate our AI platform into PCCTC studies to advance the development and validation of novel AI-enabled biomarkers.

• Prior to 2022, we also entered into several other separate agreements, including with RefleXion Medical, Inc., POINT and Regeneron Pharmaceuticals, Inc., under which we supply PYLARIFY in connection with their clinical studies.

◦ In May 2019, we commenced an initiative to build out our Pharma Services capabilities, which reside in our Strategic Partnerships and Other Revenue product category.

We have undertaken the following efforts to execute that initiative.

In May 2022, we announced that the first patient had been dosed in a Phase 2 clinical trial of NM-01, a novel technetium-99m SPECT imaging agent under development to assess PD-L1 expression in cancer cells.

The Phase 2 clinical trial is an open-label, single-arm trial in non-small cell lung cancer patients.

The primary endpoint is the assessment of PD-L1 expression in primary tumor and metastatic lesions by NM-01 compared to immunohistochemistry.

Other objectives are aimed at quantifying intra- and inter-tumoral heterogeneity of PD-L1 expression by NM-01, as well as establishing correlations with other diagnostic procedures.

The trial is being conducted by NanoMab at King’s College London and is expected to complete enrollment in 2023.

◦ Pan-Oncology - In March 2021, we acquired from Ratio Therapeutics LLC (“Ratio”) (previously Noria Therapeutics, Inc.) exclusive, worldwide rights to NTI-1309, an innovative imaging biomarker that targets fibroblast activation protein, an emerging target with broad potential imaging applicability and use in oncology.

Upon further clinical development, we will assess options to bring NTI-1309 to market as a diagnostic or potentially a therapeutic agent.

• We have also entered into several other separate agreements, including with RefleXion Medical, Inc., POINT and Regeneron Pharmaceuticals, Inc., under which we supply PYLARIFY in connection with their clinical trials and with the Prostate Cancer Clinical Trial Consortium (“PCCTC”), a premier multicenter clinical research organization that specializes in prostate cancer research.

The intent of the strategic collaboration with PCCTC is to integrate our artificial intelligence (“AI”) platform into PCCTC studies to advance the development and validation of novel AI-enabled biomarkers.

◦ Immuno-Oncology - We entered into a strategic collaboration and license agreement with NanoMab Technology Limited (“NanoMab”), a privately-held biopharmaceutical company focused on the development of next generation radiopharmaceuticals for cancer precision medicine, to develop NM-01, a novel technetium-99m SPECT imaging agent under development to assess PD-L1 expression in cancer cells.

In connection with the collaboration, NanoMab recently completed a Phase 2 clinical trial at King’s College London.

The Phase 2 clinical trial was an open-label, single-arm trial in non-small cell lung cancer patients.

The primary endpoint was the assessment of PD-L1 expression in primary tumor and metastatic lesions by NM-01 compared to immunohistochemistry.

Other objectives were aimed at quantifying intra- and inter-tumoral heterogeneity of PD-L1 expression by NM-01, as well as establishing correlations with other diagnostic procedures.

We expect results from the clinical trial to be presented at an upcoming medical congress.

◦ Pan-Oncology - In collaboration with Ratio Therapeutics LLC (“Ratio”) (previously Noria Therapeutics, Inc.), we are developing LNTH-1363S, a novel copper-64 labeled PET imaging agent, targeting fibroblast activation protein alpha.

We believe this diagnostic agent candidate could have broad potential applicability and use in oncology and also in inflammatory diseases.

Recently, in collaboration with Ratio, we completed a Phase 1 study for LNTH-1363S to evaluate the pharmacokinetics, biodistribution and radiation dosimetry in adult healthy volunteers.

We plan to initiate a Phase 1/2a study in patients in 2024.

Microbubble Franchise

In addition, we continue to seek to optimize our microbubble platform through new collaborations.

In December 2022, we announced a strategic collaboration with SonoThera, Inc.

(“SonoThera”), who will use our microbubbles in combination with their ultrasound-guided, non-viral, gene therapy platform and treatments.

Prior to 2022, we entered into microbubble collaborations with the following parties:

Some of our microbubble collaborations are with the following parties:

(i) Cerevast Medical, Inc.

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(“Insightec”), which will use our microbubbles in connection with the development of Insightec’s transcranial guided focused ultrasound device for the treatment of glioblastoma as well as other neurodegenerative conditions;

and (iv) Allegheny Health Network (“AHN”) which will use our microbubbles in combination with AHN’s ultrasound-assisted non-viral gene transfer technology for the development of a proposed treatment of xerostomia.

(iv) Allegheny Health Network (“AHN”) which will use our microbubbles in combination with AHN’s ultrasound-assisted non-viral gene transfer technology for the development of a proposed treatment of xerostomia;

and (v) SonoThera, Inc.

(“SonoThera”), who will use our microbubbles in combination with their ultrasound-guided, non-viral, gene therapy platform and treatments.

In March 2012, we entered into a development and distribution arrangement with China Resources Double-Crane (“Double-Crane”) for DEFINITY in China, Hong Kong and Macau.

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Double-Crane is also in the process of analyzing the clinical results relating to liver and kidney indications and will also work with us to prepare an Import Drug License application for those indications, as appropriate.

• Bausch Agreement -- Under its agreement with Salix Pharmaceuticals, Inc., a wholly-owned subsidiary of Bausch, Progenics received a $40.0 million development milestone upon U.S.

marketing approval for subcutaneous RELISTOR in non-cancer pain patients in 2014, a $50.0 million development milestone for the U.S.

marketing approval of an oral formulation of RELISTOR in July 2016, and a $10.0 million sales milestone for RELISTOR achieving U.S.

net sales in excess of $100.0 million in 2019.

We are also eligible to receive additional one-time sales milestone payments upon achievement of specified U.S.

MK-6240 is an investigational clinical stage F 18-labeled PET imaging development candidate designed to detect Tau protein in the form of neurofibrillary tangles in the brains of patients with known or suspected Alzheimer’s disease.

MK-6240 is being used as a

biomarker in more than 90 active clinical trials for Alzheimer’s disease therapeutic candidates.

Research revenue related to MK-6240 is derived from the use of MK-6240 in those clinical trials and includes milestone and dose-related payments.

• On August 2, 2023, we sold our right to our RELISTOR net sales royalties under our license agreement with Bausch;

we retained the rights to future sales-based milestone payments.

Pursuant to our license agreement with Bausch, we are eligible to receive one-time sales milestone payments upon achievement of specified U.S.

net sales targets, including:

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Each sales milestone payment is payable one time only, regardless of the number of times the condition is satisfied, and all five remaining payments could be made within the same calendar year.

We are also eligible to receive royalties from Bausch and its affiliates based on the following royalty scale:

15% on worldwide net sales up to $100.0 million, 17% on the next $400.0 million in worldwide net sales, and 19% on worldwide net sales over $500.0 million each calendar year, and 60% of any upfront, milestone, reimbursement or other revenue (net of costs of goods sold, as defined, and territory-specific research and development expense reimbursement) Bausch receives from sublicensees outside the U.S.

During the fourth quarter of 2023, the Company earned the $15.0 million sales-based milestone payment listed above.

• aBSI automatically calculates the disease burden of prostate cancer by detecting and classifying bone scan tracer uptakes as metastatic or benign lesions using an artificial neural network.

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on August 5, 2019.

In February 2020, Progenics received CE marking for the standalone workstation model of aBSI, meeting the quality standards set by the European Economic Area.

In February 2020, Progenics received European Conformity Marking (“CE marking”) for the standalone workstation model of aBSI, meeting the quality standards set by the European Economic Area.

In September 2020, the FDA granted 510(k) clearance for the use of aBSI as software-as-a-medical device on a GE Healthcare imaging system.

aBSI is also approved in Japan and part of the JSMO guidelines (Japanese Society of Medical Oncology) in support of clinicians with patient treatment selection.

The Japanese non-exclusive rights to aBSI have been transferred and sold to FUJIFILM Toyama Chemical Co.

(“FUJIFILM”) under the name BONENAVI ® .

• PYLARIFY AI is artificial intelligence medical device software that is designed to allow healthcare professionals and researchers to perform standardized quantitative assessment of PSMA PET/CT images in prostate cancer, including those images obtained by using PYLARIFY.

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Once deployed, the adaptive application can be integrated into an institution’s existing clinical workflow, delivering a unique combination of clinical utility and technical flexibility.

We believe that PYLARIFY AI when used with PYLARIFY will provide us an important competitive advantage in what we expect will be a highly competitive PET PSMA diagnostic imaging agent market, although we can give no assurances to that effect.

Our subsidiary, EXINI, was granted 510(k) clearance by the FDA in the U.S.

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[ 18 F] flurpiridaz

• GE Healthcare Agreement – In April 2017, we announced entering into a definitive, exclusive Collaboration and License Agreement with GE Healthcare for the continued Phase 3 development and worldwide commercialization of flurpiridaz, a fluorine 18-based PET MPI agent designed to assess blood flow to the heart in patients suspected of coronary artery disease (“CAD”).

Under our agreement, GE Healthcare will complete the development of flurpiridaz, pursue worldwide regulatory

approvals, and, if successful, lead a worldwide launch and commercialization of the agent, with us collaborating on both development and commercialization through a joint steering committee.

• GE Healthcare Agreement – In 2017, we entered into a definitive, exclusive Collaboration and License Agreement with GE Healthcare for the continued Phase 3 development and worldwide commercialization of flurpiridaz, a fluorine 18-based PET MPI agent designed to assess blood flow to the heart in patients suspected of coronary artery disease (“CAD”).

Under our agreement, GE Healthcare will complete the development of flurpiridaz, pursue worldwide regulatory approvals, and, if successful, lead a worldwide launch and commercialization of the agent, with us collaborating on both development and commercialization through a joint steering committee.

We also have retained the right to co-promote the agent in the U.S.

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In September 2022, we announced with GE Healthcare that the second Phase 3 clinical trial had met its co-primary endpoints of exceeding a 60% threshold for both sensitivity and specificity for detecting CAD.

The findings, shared at an American Society of Nuclear Cardiology conference, also indicated that cardiac PET imaging with flurpiridaz demonstrated higher diagnostic efficacy and image quality in patients with suspected CAD, compared with SPECT MPI, the predominant procedure currently used in nuclear cardiology.

Assuming regulatory approval, we anticipate commercialization beginning in 2024.

The findings,

shared at an American Society of Nuclear Cardiology conference, also indicated that cardiac PET imaging with flurpiridaz demonstrated higher diagnostic efficacy and image quality in patients with suspected CAD, compared with SPECT MPI, the predominant procedure currently used in nuclear cardiology.

GE Healthcare recently announced that it had filed an NDA with the FDA for flurpiridaz.

Assuming regulatory approval, we anticipate commercialization by GE Healthcare beginning in the second half of 2024.

See Part I, Item 1A.

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In addition to our commercial products and strategic partnerships with third parties, we also have ongoing clinical development programs, including, among others, the following:

• PNT2002 is a prostate-specific membrane antigen-targeted radiopharmaceutical therapy for the treatment of mCRPC.

PNT2002 is currently in its Phase 3 study, designed to evaluate superiority to the standard of care in mCRPC pre-chemotherapy patients who have failed one androgen receptor pathway inhibitor.

• PNT2003 is an SSTR therapy with non-carrier added lutetium-177, which is in development to treat patients with SSTR-positive neuroendocrine tumors.

PNT2003 is currently in a Phase 3 trial.

• 1095 (also known as 131 I-MIP-1095) is a PSMA-targeted iodine-131-labeled small molecule that is designed to deliver a dose of beta radiation directly to prostate cancer cells with minimal impact on the surrounding healthy tissues.

• PNT2002 is an investigational PSMA-targeted radiopharmaceutical therapy for the treatment of mCRPC.

On December 18, 2023, we announced positive topline results from SPLASH, the Phase 3 registrational trial for PNT2002 designed to evaluate superiority to the standard of care in mCRPC pre-chemotherapy patients who have failed one androgen receptor pathway inhibitor.

• PNT2003 is an investigational SSTR therapy with non-carrier added lutetium-177, which is in registration to treat patients with SSTR-positive neuroendocrine tumors.

On January 11, 2024, we announced that our ANDA for PNT2003 was accepted for filing by the FDA.

On January 26, 2024, we were sued in the United States District Court for the District of Delaware by Advanced Accelerator Applications USA, Inc.

and Advanced Accelerator Applications SA, each a Novartis entity, for patent infringement in response to the filing of our ANDA and Paragraph IV certification, consistent with the process established by the Hatch-Waxman Act.

• MK-6240 is an investigational second-generation F 18-labeled PET imaging agent that targets Tau tangles in Alzheimer’s disease.

MK-6240 is currently being used in more than 90 active clinical trials for several Alzheimer’s disease therapeutic candidates being developed.

• LNTH-1363S is an investigational fibroblast activation protein, alpha targeted, copper-64 labeled PET imaging agent candidate that we believe could have broad potential imaging applicability and use in oncology.

Recently, we completed a Phase 1 study for LNTH-1363S to evaluate the pharmacokinetics, biodistribution and radiation dosimetry in adult healthy volunteers.

• 1095 (also known as 131 I-MIP-1095) is an investigational PSMA-targeted iodine-131-labeled small molecule that is designed to deliver a dose of beta radiation directly to prostate cancer cells with minimal impact on the surrounding healthy tissues.

We enrolled the last patient in our ARROW Phase 2 study during the second quarter of 2022.

In total, 120 patients have been randomized -- 80 in the 1095 plus enzalutamide combination group and 40 in the enzalutamide alone group.

This study is a multicenter, randomized, open-label, controlled Phase 2 clinical study evaluating the efficacy and safety of 1095, our PSMA-targeted I-131 therapeutic, in combination with enzalutamide compared to enzalutamide alone in patients with metastatic castration resistant prostate cancer who are PSMA-avid, chemotherapy naïve, and have progressed on abiraterone.

The primary endpoint in this study is PSA response rate.

Key secondary endpoints include time to radiographic free progression, progression free survival, and overall survival.

Patients in this study will be followed for one year after their first treatment for all efficacy endpoints and survival and safety data will be collected for an additional year.

For the years ended December 31, 2023, 2022 and 2021, we invested $77.7 million, $311.7 million and $45.0 million in research and development (“R&D”), respectively, primarily related to our clinical development candidates.

For the year ended December 31, 2022, we recognized $260.0 million of R&D expense related to the upfront payments to POINT.

In addition to our clinical development group, our R&D team also includes our Medical Affairs and Medical Information functions, which educate physicians on the scientific aspects of our commercial products and the approved indications.

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Product Approved Markets

Precision Diagnostics

DEFINITY (or LUMINITY) Australia, Canada, China, European Union, European Economic Area, India, Israel, Mexico, New Zealand, Singapore, South Korea, Taiwan, United Kingdom, United States

TechneLite Australia, Brazil, Canada, Colombia, Costa Rica, New Zealand, Panama, South Korea, Taiwan, United States

NEUROLITE Australia, Austria, Belgium, Canada, Costa Rica, Denmark, France, Germany, Hong Kong, Italy, Japan, Luxembourg, New Zealand, Philippines, Slovenia, South Korea, Spain, Taiwan, Thailand, United States

Xenon Canada, United States

CARDIOLITE Australia, Canada, Costa Rica, Hong Kong, Israel, Japan, New Zealand, Panama, Philippines, South Korea, Taiwan, Thailand, United States

Radiopharmaceutical Oncology

PYLARIFY United States

AZEDRA United States

PYLARIFY European Union*, United States

Precision Diagnostics

DEFINITY (or LUMINITY) Australia, Canada, China, European Union, European Economic Area, Israel, New Zealand, United Kingdom, United States

DEFINITY RT United States

TechneLite Australia, Canada, Colombia, Costa Rica, South Korea, Taiwan, United States

NEUROLITE Australia, Belgium, Canada, Costa Rica, Denmark, France, Hong Kong, Italy, Japan, Luxembourg, South Korea, Spain, Taiwan, United States

Xenon United States

CARDIOLITE Australia, Canada, Israel, Japan, New Zealand, South Korea, Taiwan, United States

Strategic Partnerships and Other Revenue

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RELISTOR (methylnaltrexone bromide) Oral Tablet 140 mg United States

*Approved under the name PYLCLARI and licensed to Curium.

With respect to our medical devices:

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PYLARIFY sales are generated in the U.S.

through a PYLARIFY direct sales team and a sales team at some of our PMF partners.

through an internal PYLARIFY sales team, as well as a sales team at some of our PMF partners.

Sales of DEFINITY are generated in the U.S.

through a DEFINITY direct sales team.

through an internal DEFINITY sales team.

While a small portion of our nuclear imaging product sales in the U.S.

are generated through our direct sales force to hospitals and clinics that maintain their own in-house radiopharmaceutical preparation capabilities, we primarily sell our nuclear imaging products, including TechneLite, NEUROLITE, Xenon, and CARDIOLITE, to large radiopharmacy groups.

We have licensed RELISTOR to Bausch, and we collect quarterly royalties based on sales generated by Bausch.

AZEDRA sales are generated in the U.S.

through an AZEDRA direct sales team.

PYLARIFY AI sales leads are generated in the U.S.

through a direct sales team with sales generated through distributors and other strategic partners.

are generated through our internal sales force to hospitals and clinics that maintain their own in-house radiopharmaceutical preparation capabilities, we primarily sell our nuclear imaging products, including TechneLite, NEUROLITE, Xenon, and CARDIOLITE, to large radiopharmacy chains.

We have licensed RELISTOR to Bausch, and while we have sold the right to our RELISTOR net sales royalties under our license agreement, we have retained the rights to future sales-based milestone payments generated by Bausch.

We have some modest seasonality for our products as patients may seek to schedule diagnostic imaging and other procedures less frequently during the summer vacation months and over the year-end holidays.

No customer accounted for greater than 10% of revenues for the year ended December 31, 2022.

No customer accounted for greater than 10% of revenues for the years ended December 31, 2023, 2022, and 2021.

Our backlog consists of orders for which a delivery schedule within the next twelve months has been specified.

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Our principal competitors for our current commercial products and leading clinical development candidates include large, global companies that are more diversified than we are and that have substantial financial, manufacturing, sales and marketing, distribution and other resources.

• For PYLARIFY, our principal competitors are currently Telix Pharmaceuticals Limited and Novartis AG.

We also face potential competition from an F 18 PSMA PET imaging agent for which Bracco is currently seeking FDA approval, which we believe could be granted by the FDA in 2023.

• For PYLARIFY, our principal competitors are currently Telix Pharmaceuticals Limited, Novartis AG, and Blue Earth Diagonstics Ltd.

(“Blue Earth”), a subsidiary of Bracco Diagnostics Inc.

• For DEFINITY, our competitors currently include GE Healthcare and Bracco.

• For a number of our SPECT radiopharmaceutical commercial products, our competitors currently include Curium, GE Healthcare, Bracco and Jubilant Life Sciences, an affiliate of JHS and Jubilant Radiopharma, as well as other competitors, including NorthStar and potentially BWXT Medical.

• For RELISTOR, our principal competitors include RedHill Biopharma Inc., in collaboration with AstraZeneca PLC;

Cubist Pharmaceuticals, a subsidiary of Merck & Co., Inc.;

Mallinckrodt plc, in collaboration with Takeda Pharmaceutical Company Limited;

and BioDelivery Sciences International, Inc.;

together with other prescription, as well as over-the-counter, laxatives used as first line therapy for OIC.

• For AZEDRA, while there are currently no other FDA approved anticancer treatments in the U.S.

for malignant, recurrent, and/or unresectable pheochromocytoma and paraganglioma, our competitors include developers of anticancer treatments currently used, but not specifically FDA approved for treatment of malignant, recurrent, and/or unresectable pheochromocytoma and paraganglioma.

The markets into which any of our product candidates would be launched, if approved, are also highly competitive and continually evolving.

• For PNT2002 and 1095, our principal competitors in the field of mCRPC for radiopharmaceutical therapeutics may include Novartis AG;

• For PNT2002 and 1095, our principal competitors may include Novartis AG;

Telix Pharmaceuticals Limited;

Curium and Bayer HealthCare Pharmaceuticals Inc., each of which have product candidates in development.

and Curium, each of which has commercialized products or product candidates in advanced clinical stage of development.

• For PNT2003, our principal competitor may include Novartis AG;

• For flurpiridaz, our principal competitors may include rubidium generators from Bracco and Jubilant Radiopharma.

We cannot anticipate the actions of our current or future competitors in the same or competing diagnostic modalities, such as significant price reductions on products that are comparable to our own, development of new products or other technologies that are more cost-effective or have superior performance than our current products or the introduction of generic versions after our proprietary products lose their patent protection.

In addition, distributors of our products could attempt to shift end-users to competing diagnostic modalities and products, or bundle the sale of a portfolio of products, to the detriment of our specific products.

ITM Radiopharma;

and RayzeBio (under agreement to be acquired by Bristoll Meyers Squibb), each of which has commercialized products or product candidates in advanced clinical stage development.

• For MK-6240, our principal competitors may include Eli Lilly and Company and Life Molecular Imaging, each of which has commercialized products or product candidates in advanced clinical stage of development.

• For LNTH-1363S, our principal competitors may include Sofie Bioscience;

GE Healthcare;

and Novartis AG, each of which has product candidates in clinical stage of development.

We cannot anticipate the actions of our current or future competitors in the same or competing therapeutic and diagnostic modalities, such as significant price reductions on products that are comparable to our own, development of new products or other technologies that are more cost-effective or have superior performance than our current products or the introduction of generic versions after our proprietary products lose their patent protection.

In addition, distributors of our products could attempt to shift end-users to competing modalities and products, or bundle the sale of a portfolio of products, to the detriment of our specific products.

Our current or future products could be rendered obsolete or uneconomical as a result of these activities.

Further, the radiopharmaceutical and biopharmaceutical industry continues to evolve strategically, with several market participants either recently sold or for sale.

In addition, the supply-demand dynamics of the industry are complex because of large market positions of some participants, legacy businesses, government subsidies (in particular, relating to the manufacture of radioisotopes), and group purchasing arrangements.

Further, the radiopharmaceutical and biopharmaceutical industry continues to evolve strategically, with several market participants recently sold.

We cannot predict what impact new owners and new operators may have on the strategic decision-making of our competitors, customers and suppliers.

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The IRE Agreement also requires IRE to provide certain favorable allocations of Mo-99 during periods of supply shortage or failure.

The IRE Agreement also provides for an increased supply of Mo-99 derived from LEU targets upon IRE’s completion of its ongoing conversion program to modify its facilities and processes in accordance with Belgian nuclear security commitments.

The IRE Agreement allows for termination upon the occurrence of certain events, including failure by IRE to provide our required amount of Mo-99, material breach of any provision by either party, bankruptcy by either party or force majeure events.

The IRE Agreement expires on December 31, 2024, and automatically renews on an annual basis thereafter, subject to prior notice of non-renewal by either party.

Our agreement with NTP (the “NTP Agreement”), with NTP acting for itself and on behalf of its subcontractor ANSTO, specifies our percentage purchase requirements and unit pricing, and provides for the supply of Mo-99 derived from LEU targets from NTP and ANSTO.

The NTP Agreement allows for termination upon the occurrence of certain events, including failure by NTP to provide our required amount of Mo-99, material breach of any provision by either party, bankruptcy by either party or force majeure events.

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A prolonged disruption of service from one of our three Mo-99 processing sites or one of their main Mo-99-producing reactors could have a substantial negative effect on our business, results of operations, financial condition and cash flows.

To augment our current supply of Mo-99, we have a strategic arrangement with SHINE Technologies LLC (“SHINE”) for the future supply of Mo-99.

Under the terms of the supply agreement, entered into in November 2014, SHINE will provide Mo-99 produced using its proprietary LEU-solution technology for use in our TechneLite generators once SHINE’s facility becomes operational and receives all necessary regulatory approvals, which SHINE now estimates will occur in 2024.

The term of this arrangement provides for three years of supply of Mo-99.

However, we cannot assure you that SHINE will be able to produce commercial quantities of Mo-99 for our business, or that SHINE, together with our current suppliers, will be able to deliver a sufficient quantity of Mo-99 to meet our needs.

Xenon is a by-product of the Mo-99 production process.

Under a strategic agreement entered into in 2021, we receive from IRE bulk unprocessed Xenon, which we process and finish for our customers at our North Billerica, Massachusetts manufacturing facility.

That contract runs through December 31, 2023, with auto-renewal provisions and terminable upon notice of non-renewal.

That contract runs through December 31, 2025, with auto-renewal provisions and is terminable upon notice of non-renewal.

Until we can qualify an additional source of bulk unprocessed Xenon, we will rely on IRE as a sole source provider.

Iodine 131 is also a by-product of the Mo-99 production process, and it is the active radioisotope ingredient in both AZEDRA and 1095.

We receive Iodine 131 from IRE in Belgium and NTP in South Africa.

We use Iodine 131 at our Somerset facility to manufacture and produce AZEDRA.

We also rely on Center for Probe Development and Commercialization (“CPDC”) in Canada for our clinical supply requirements for 1095.

CPDC sources Iodine 131 from IRE in Belgium and NTP in South Africa.

Other Materials

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Because each of the PMFs manufacturing PYLARIFY is deemed by the FDA to be a separate manufacturing site, each requires separate FDA approval.

Flurpiridaz, if approved by the FDA, will have a manufacturing and PMF approval process similar to PYLARIFY.

We have a specialized in-house manufacturing facility at our North Billerica campus for purposes of producing DEFINITY and, potentially, other sterile vial products.

On February 22, 2022, we received FDA approval of our sNDA, authorizing commercial manufacturing of DEFINITY at our new facility.

We have a specialized in-house manufacturing facility at our North Billerica campus for purposes of producing the formulation of DEFINITY that requires refrigerated storage and, potentially, other sterile vial products.

On February 22, 2022, we received FDA

approval of our sNDA, authorizing commercial manufacturing of DEFINITY at our new facility.

DEFINITY manufactured at this facility became commercially available on February 23, 2022.

We believe this investment will allow us to better manage DEFINITY manufacturing and inventory, reduce our costs in a potentially more price competitive environment, and provide us with supply chain redundancy.

We also manufacture TechneLite on a highly automated production line and we process and finish Xenon on a hot cell line at our North Billerica, Massachusetts facility.

We also operate a manufacturing facility at Somerset, NJ, using a hot cell line for AZEDRA.

During 2021, we increased the manufacturing staff at our Somerset facility to help maintain an adequate supply of AZEDRA.

We also began constructing an additional manufacturing suite at Somerset which, if approved by the FDA, could provide redundancy for AZEDRA manufacturing as well as increased overall future capacity for 1095, if approved by the FDA or other iodine-based products.

We believe this investment provides supply chain redundancy, improved flexibility and reduced costs in a potentially more price competitive environment.

We also manufacture TechneLite on an automated production line and we process and finish Xenon on a hot cell line at our North Billerica, Massachusetts facility.

We manufacture, finish and distribute our radiopharmaceutical products on a just-in-time basis, and supply our customers with these products either by next day delivery services or by either ground or air custom logistics.

We believe that our substantial capital investments in our highly automated generator production line and our other manufacturing assets, which we have made over the years, and our extensive experience in complying with the stringent regulatory requirements for the handling of nuclear materials and operations in a highly regulated environment, create significant and sustainable competitive advantages for us.

We believe that our substantial capital investments in our automated generator production line and our other manufacturing assets, which we have made over the years, and our extensive experience in complying with the stringent regulatory requirements for the handling of nuclear materials and operations in a highly regulated environment, create significant and sustainable competitive advantages for us.

In addition to our in-house manufacturing capabilities, a substantial portion of our products are manufactured by third party contract manufacturing organizations, and in certain instances, we rely on them for sole source manufacturing.

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For many of our products, after the final products are manufactured, they are sent back to us for final quality control testing, and then we ship them to our customers.

We have expertise in the design, development and validation of complex manufacturing systems and processes, and our strong execution and quality control culture supports the just-in-time manufacturing model at our manufacturing facilities.

Manufacturing and Supply Arrangements

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• PYLARIFY —We have entered into commercial supply agreements with different PMF networks.

Our agreements with our PMF networks allow for the termination upon the occurrence of specified events, including material breach or bankruptcy by either party, and have various termination dates generally terminating between 2025 to 2027 and subject to renewal provisions.

• DEFINITY, CARDIOLITE and NEUROLITE —In February 2022, we entered into a new Manufacturing and Supply Agreement with JHS, for the manufacture of DEFINITY, CARDIOLITE, NEUROLITE and evacuation vials.

The new agreement, which superseded all of our prior agreements with JHS for those products, expires on December 31, 2027, and can be renewed upon mutual consent.

• DEFINITY, CARDIOLITE and NEUROLITE —In February 2022, we entered into a Manufacturing and Supply Agreement with JHS, for the manufacture of DEFINITY, CARDIOLITE, NEUROLITE and evacuation vials, the latter being an ancillary component for our TechneLite generators.

The agreement expires on December 31, 2027, and can be renewed upon mutual consent.

The agreement allows for termination upon the occurrence of certain events such as a material breach or default by either party, or bankruptcy by either party.

The agreement also requires us to order from JHS a specified minimum percentage of our requirements for DEFINITY and fixed quantities of CARDIOLITE and NEUROLITE each year during the contract term.

Based on our current projections, we believe that we will have sufficient supply of DEFINITY from JHS and our in-house manufacturing facility and sufficient supply of CARDIOLITE and NEUROLITE products from JHS to meet expected demand.

See Part I, Item 1A.

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If we do not obtain sufficient protection for our intellectual property, or if we are unable to effectively enforce or defend our intellectual property rights or our freedom to operate, our competitiveness could be impaired, which would limit our growth and future revenue.

If we elect to enforce our intellectual property rights, or are required to defend our rights, we could incur significant litigation expense.

Trademarks, Service Marks and Trade Names

We own various trademarks, service marks and trade names, including, among others, PYLARIFY, DEFINITY, AZEDRA and Find.Fight.Follow.

We own various trademarks, service marks and trade names, including, among others, PYLARIFY, DEFINITY and Find Fight and Follow.

We have generally registered these trademarks, as well as others, in the U.S.

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and internationally.

for PYLARIFY, we have four Orange Book-listed patents, including composition of matter patents, the last of which expire in 2037.

for PYLARIFY, we have five Orange Book-listed patents, including composition of matter patents, the last of which expire in 2037.

Outside of the U.S., we have, and are currently pursuing, additional PYLARIFY patents to obtain similar patent protection as in the U.S.

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and internationally.

for DEFINITY RT, we have eight Orange Book-listed patents, including two composition of matter patents which expire in 2035.

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Even though our longest duration Orange Book-listed DEFINITY patent extends until March 2037, because our Orange Book-listed composition of matter patent expired in June 2019, we may face generic DEFINITY challengers in the near to intermediate term.

Under the Hatch-Waxman Act, the FDA can approve Abbreviated New Drug Applications (“ANDAs”) for generic versions of drugs if the ANDA applicant demonstrates, among other things, that (i) its generic candidate is the same as the innovator product by establishing bioequivalence and providing relevant chemistry, manufacturing and product data, and (ii) either the marketing of that generic candidate does not infringe the Orange Book-listed patent(s) or the Orange Book-listed patent(s) is invalid.

Under the Hatch-Waxman Act, the FDA can approve ANDAs for generic versions of drugs if the ANDA applicant demonstrates, among other things, that (i) its generic candidate is the same as the innovator product by establishing bioequivalence and providing relevant chemistry, manufacturing and product data, and (ii) either the marketing of that generic candidate does not infringe the Orange Book-listed patent(s) or the Orange Book-listed patent(s) is invalid.

Similarly, the FDA can approve a Section 505(b)(2) NDA from an applicant that relies on some of the information required for marketing approval to come from studies which the applicant does not own or have a legal right of reference.

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The 30-month stay could potentially expire sooner if the courts determine that no infringement had occurred or that the challenged Orange Book-listed patent is invalid or if the parties otherwise settle their dispute.

Submission of an ANDA with a Paragraph IV certification can result in protracted and expensive patent litigation.

As of the date of filing of this Annual Report on Form 10-K, we have not received any Notice from an Applicant.

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If we received a Notice some number of months in the future and the full 30-month stay were obtained, the commercialization date would roll forward in the future by the same number of months.

In the event a 505(b)(2) applicant does not rely on studies related to the innovator product, the 30-month stay would not apply, but additional clinical studies may be required.

In the event a 505(b)(2) applicant does not rely on studies related to the innovator product, the 30-month stay would not apply, but additional clinical trials may be required.

TechneLite - We currently own patents in the U.S.

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that expires in October 2035 for an improved container for Xenon, and are pursuing similar patent protection outside the U.S.

RELISTOR - Although the composition of matter patent for the active ingredient, methylnaltrexone, has expired, there are additional patents and pending patent applications covering various inventions relating to the product.

There are eight Orange Book listed patents that cover the subcutaneous RELISTOR product, which have expiration dates ranging from 2024 to 2030, and there are nine Orange Book listed patents that cover the RELISTOR tablet product, which have expiration dates ranging from 2029 to 2031.

Progenics has entered into four separate settlement agreements that have granted non-exclusive limited licenses with respect to certain RELISTOR subcutaneous injection applications.

The non-exclusive limited licenses with three parties are currently effective on January 1, 2028 and the fourth non-exclusive limited license is currently effective on July 1, 2028, in each case, subject to potential acceleration clauses in those agreements.

Four Canadian patents (two expiring in 2024, one in 2027 and one in 2029) have been listed with Health Canada relating to subcutaneous RELISTOR.

AZEDRA - The AZEDRA technology patent family was licensed from the University of Western Ontario (“UWO”).

While certain of those patents, and associated license, have already expired, a patent relating to alternative approaches for preparing AZEDRA (not currently implemented) expires worldwide in 2024.

In addition, we own patents and pending applications worldwide for precursors, pharmaceutical compositions, kits, and manufacturing improvements, including in the U.S.

a manufacturing method expiring in 2035.

aBSI - We own patents relating to automated detection of bone cancer metastases.

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directed to formulations, use and manufacturing of PNT2003 which, if granted, would expire in 2041.

1095 - We own patents relating to 1095 that expire from 2027 to 2031, with the composition of matter as well as radiolabeled forms in the U.S.

MK-6240 - We exclusively license patents directed to composition of matter and methods of use of MK-6240 which expire in 2035.

1095 - We own patents relating to 1095, with the composition of matter patent as well as radiolabeled forms patent in the U.S.

and Europe expiring in 2027.

Additional U.S.

patents for stable compositions and radiolabeling processes expire, respectively, in 2030 and 2031.

patents that we own for stable compositions and radiolabeling processes expire, respectively, in 2030 and 2031.

LNTH-1363S - We exclusively license patent applications directed to compositions of matter and methods of use of LNTH-1363S.

If granted, the last patent will expire in 2043.

NM-01 - We exclusively license in the field of imaging, patents and applications directed to compositions of matter of NM-01.

The granted U.S.

patents expire in 2037.

1404 - We own patents relating to composition of matter, as well as technetium-99 labeled forms of 1404 expiring in the U.S.

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A number of factors substantially increase the time, difficulty and costs incurred in obtaining and maintaining the approval to market newly developed and existing products.

These factors include governmental regulation, such as detailed inspection of and controls over research and laboratory procedures, clinical investigations, manufacturing, marketing, sampling, distribution, import and export, record keeping and storage and disposal practices, together with various post-marketing requirements.

These factors include governmental regulation, such as detailed inspection of and controls over research and laboratory procedures, clinical trials, manufacturing, marketing, advertising and promotion, sampling, distribution, import and export, record keeping and storage and disposal practices, together with various post-marketing requirements.

Governmental regulatory actions can result in the seizure or recall of products, suspension or revocation of the authority necessary for their production and sale as well as other civil or criminal sanctions.

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• Completion of preclinical laboratory tests, animal studies and formulation studies according to current Good Laboratory Practices regulations;

• Submission to the FDA of an investigational new drug application (“IND”) which must become effective before human clinical studies may begin, including review and approval by any institutional review board (“IRB”), serving any of the institutions participating in the clinical studies;

• Performance of adequate and well-controlled human clinical studies according to current Good Clinical Practices and other requirements, to establish the safety and efficacy of the proposed drug product for its intended use;

• Submission to the FDA of a new drug application (“NDA”) for a new drug;

• Submission to the FDA of an investigational new drug application (“IND”) which must become effective before human clinical trials may begin, including review and approval by any institutional review board (“IRB”), serving any of the institutions participating in the clinical trials;

• Performance of adequate and well-controlled human clinical trials according to current Good Clinical Practices and other requirements, to establish the safety and efficacy of the proposed drug product for its intended use;

• Submission to the FDA of an NDA for a new drug;

• Satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug product is produced to assess compliance with current Good Manufacturing Practices (“cGMPs”) regulations;

• FDA review and approval of the NDA.

The testing and approval process requires substantial time, effort, and financial resources, and we cannot be certain that any approvals for our agents in development will be granted on a timely basis, if at all.

Once a pharmaceutical agent is identified for development, it enters the preclinical testing stage.

The testing and approval process requires substantial time, effort, and financial resources, and we cannot be certain that any approvals for our products in development will be granted on a timely basis, if at all.

Once a pharmaceutical product is identified for development, it enters the preclinical testing stage.

Preclinical tests include laboratory evaluations of product chemistry, toxicity, formulation, and stability, as well as animal studies to assess its potential safety and efficacy.

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Once the IND becomes effective, including review and approval by any IRB serving any of the institutions participating in the clinical trial, the clinical trial program may begin.

Each new clinical trial protocol must be submitted to the FDA before the study may begin.

Human clinical studies are typically conducted in three sequential phases that may overlap or be combined:

The agent is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion.

In the case of some products for severe or life-threatening diseases, especially when the agent may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients with those diseases.

Involves studies in a limited patient population to identify possible adverse effects and safety risks, to evaluate preliminarily the efficacy of the agent for specific targeted diseases and to determine dosage tolerance and optimal dosage and schedule.

Clinical studies are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical study sites.

These studies are intended to collect sufficient safety and efficacy data to support the NDA for FDA approval.

Progress reports detailing the results of the clinical studies must be submitted at least annually to the FDA and safety reports must be submitted to the FDA and the investigators for serious and unexpected adverse events.

Each new clinical trial protocol must be submitted to the FDA before the trial may begin.

The person, entity or organization taking responsibility for the trial is referred to as the clinical trial sponsor.

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

The product is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion.

In the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients with those diseases.

Involves trials in a limited patient population to identify possible adverse effects and safety risks, to evaluate preliminarily the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage and schedule.

Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical trial sites.

These trials are intended to collect sufficient safety and efficacy data to support the NDA for FDA approval.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and safety reports must be submitted to the FDA and the investigators for serious and unexpected adverse events.

Submissions must also be made to inform the FDA of certain changes to the clinical trial protocol.

Federal law also requires the sponsor to register the trials on public databases when they are initiated, and to disclose the results of the trials on public databases upon completion.

Phase 1, Phase 2 and Phase 3 testing may not be completed successfully within any specified period, if at all.

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

Similarly, any IRB serving any of the institutions participating in the clinical trial can suspend or terminate approval of a clinical study at a relevant institution if the clinical study is not being conducted in accordance with the IRB’s requirements or if the agent has been associated with unexpected serious harm to patients.

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

The FDA or the clinical trial sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being

exposed to an unacceptable health risk.

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

Failure to register a clinical trial or disclose study results within the required time periods could result in penalties, including civil monetary penalties.

Concurrent with clinical studies, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the product and 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 agent and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final product.

Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the agent does not undergo unacceptable deterioration over its shelf life.

The results of product development, preclinical studies and clinical studies, along with descriptions of the manufacturing process, analytical tests conducted on the drug product, proposed labeling, and other relevant information, are submitted to the FDA as part of an NDA for a new drug, requesting approval to market the agent.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the product and 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 product and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final product.

Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product does not undergo unacceptable deterioration over its shelf life.

The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the drug product, proposed labeling, and other relevant information, are submitted to the FDA as part of an NDA for a new drug, requesting approval to market the product.

The submission of an NDA is subject to the payment of a substantial user fee.

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The FDA has substantial discretion in the product approval process, and it is impossible to predict whether and when the FDA will grant marketing approval.

The FDA may on occasion require the sponsor of an NDA to conduct additional clinical studies or to provide other scientific or technical information about the product, and these additional requirements may lead to unanticipated delay or expense.

The FDA may on occasion require the sponsor of an NDA to conduct additional clinical trials or to provide other scientific or technical information about the product, and these additional requirements may lead to unanticipated delay or expense.

Even if such data and information are submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval.

Data obtained from clinical studies are not always conclusive, and the FDA may interpret data differently than we interpret the same data.

Data obtained from clinical trials are not always conclusive, and the FDA may interpret data differently than we interpret the same data.

If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.

Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling.

In addition, the FDA may require Phase 4 testing which involves clinical studies designed to further assess a drug product’s safety and effectiveness after NDA approval.

In addition, the FDA may require Phase 4 testing which involves clinical trials designed to further assess a drug product’s safety and effectiveness after NDA approval.

The FDA also may impose one or more Risk Evaluation and Mitigation Strategies (“REMS”) to ensure that the benefits of a product outweigh its risks.

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Under the Orphan Drug Act, the FDA may designate a product as an Orphan Drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.

AZEDRA currently has the Orphan Drug designation in the United States.

In the United States, Orphan Drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.

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Later discovery of previously-unknown problems with a product may result in restrictions on the product or even complete withdrawal of the product from the market.

Further, the failure to maintain compliance with regulatory requirements may result in administrative or judicial actions, such as fines, civil monetary penalties, warning letters, holds on clinical studies, product recalls or seizures, product detention or refusal to permit the import or export of products, refusal to approve pending applications or supplements, restrictions on marketing or manufacturing, injunctions, or civil or criminal penalties.

Further, the failure to maintain compliance with regulatory requirements may result in administrative or judicial actions, such as fines, civil monetary penalties, warning letters, holds on clinical trials, product recalls or seizures, product detention or refusal to permit the import or export of products, refusal to approve pending applications or supplements, restrictions on marketing or manufacturing, injunctions, or civil or criminal penalties.

Regulations are subject to change as a result of legislative, administrative or judicial action, which may also increase our costs or reduce sales or otherwise adversely impact our products.

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We have ongoing conversations with third-party payors to advocate for appropriate coding, coverage and payment for our portfolio of products.

Medicare Outpatient Pass-Through Payment Status

Medicare Outpatient TPT Status

Part B of the Medicare program generally reimburses medical services and supplies, including drugs, provided to beneficiaries by physicians and other qualified healthcare professionals.

Generally, drugs furnished “incident to” a physician’s service in the hospital outpatient setting of care are reimbursed at Average Sales Price (“ASP”) plus a certain additional percent, unless the product is treated as a “supply” in the performance of the procedure and “packaged” and paid as part of bundled payment for the procedure.

Novel drugs, however, may apply for “pass-through status” in which case they are provided a separate payment at ASP plus a certain additional percent for two to three years, regardless of whether they would ordinarily be packaged.

PYLARIFY has received pass-through status effective January 1, 2022 through December 31, 2024, thereby providing separate reimbursement to customers using PYLARIFY in the hospital outpatient setting during this specified period.

Novel drugs, however, may apply for TPT Status in which case they are provided a separate payment at ASP plus a certain additional percent for two to three years, regardless of whether they would ordinarily be packaged.

PYLARIFY has received TPT Status effective January 1, 2022 through December 31, 2024, thereby providing separate reimbursement to customers using PYLARIFY in the hospital outpatient setting during this specified period.

The reimbursement rate for PYLARIFY was initially based on the wholesale acquisition cost (WAC) plus three percent until ASP could be established.

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Under existing Medicare policy for the hospital outpatient setting of care, non-pass-through diagnostic radiopharmaceuticals are not separately paid and are instead packaged into payment for the underlying procedure.

Therapeutic radiopharmaceuticals are paid separately by Medicare OPPS regardless of pass-through status.

We plan to continue our advocacy efforts with CMS and private insurers so that PYLARIFY customers will have appropriate and adequate reimbursement following the expiration of pass-through status.

Therapeutic radiopharmaceuticals are paid separately by Medicare OPPS regardless of TPT Status.

We plan to continue our advocacy efforts with CMS and private insurers so that PYLARIFY customers will have appropriate and adequate reimbursement following the expiration of TPT Status.

We are also supporting trade associations in their efforts to have Congress pass the Facilitating Innovative Nuclear Diagnostics (FIND) Act, which would allow for separate payment for certain diagnostic radiopharmaceuticals, including PYLARIFY, similar to the way Medicare OPPS currently pays for other drugs, biologics, and therapeutic radiopharmaceuticals instead of under the current TPT structure of a separate payment that is limited to three years.

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The IRA also introduces rebate obligations for manufacturers of Part B and D drugs that take price increases which exceed the rate of inflation, similar to the longstanding Medicaid inflation rebates.

Under these new Medicare inflation rebates, each Part B and D single-source drug/biological and biosimilar will have an “inflation adjusted” payment amount calculated by CMS.

Under these new Medicare inflation rebates, each Part B and D

single-source drug/biological and biosimilar will have an “inflation adjusted” payment amount calculated by CMS.

If the manufacturer’s price increases for the relevant product exceeds the inflation adjusted payment amount, as trended forward by the rate of inflation, the manufacturer will be required to reimburse Medicare the difference between what Medicare paid for the product and what it would have paid based on the inflation adjusted payment amount.

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We are subject to various federal, state and local laws targeting fraud and abuse in the healthcare industry, including anti-kickback and false claims laws.

Patient assistance programs, if not properly implemented, can implicate these laws.

Violations of fraud and abuse laws may be punishable by criminal or civil sanctions, including fines and civil monetary penalties, and/or exclusion from federal health care programs (including Medicare and Medicaid).

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In addition, every state in the United States now has a data breach notification law that requires regulated entities to report certain security breaches to affected data subjects, regulators, or other entities.

Failure to comply with data protection laws and regulations could result in government enforcement actions (which could include civil or criminal penalties and requirements to take corrective

actions), private litigation (which may result in the award of damages against us), and/or adverse publicity, and could negatively affect our operating results, business, and reputation.

Failure to comply with data protection laws and regulations could result in government enforcement actions (which could include civil or criminal penalties and requirements to take corrective actions), private litigation (which may result in the award of damages against us), and/or adverse publicity, and could negatively affect our operating results, business, and reputation.

In addition, we may obtain health information from third parties (e.g., healthcare providers who prescribe our products) that are themselves subject to privacy, security, and breach notification requirements under the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act (collectively, “HIPAA”).

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It also provides California residents a private right of action, including the ability to seek statutory damages, in the event of a breach involving their personal information resulting from a business’s failure to implement and maintain reasonable security procedures and practices.

Compliance with the CCPA is 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.

Compliance with the CCPA, and similar laws implemented in other states, is 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.

On November 3, 2020, California passed the California Privacy Rights Act (“CPRA”) through a ballot initiative.

The CPRA amends the CCPA and expands its protections for personal information, including by establishing a new California Privacy Protection Agency to enforce the CPRA and by providing California consumers various rights such as the right to restrict the processing of their “sensitive personal information.” The CPRA’s amendments to the CCPA take effect on January 1, 2023, and generally will apply to personal information collected by regulated businesses on or after January 1, 2022.

The CPRA amends the CCPA and expands its protections for personal information, including by establishing a new California Privacy Protection Agency to enforce the CPRA and by providing California consumers various rights such as the right to restrict the processing of their “sensitive personal information.” The CPRA’s amendments to the CCPA took effect on January 1, 2023, and generally apply to personal information collected by regulated businesses on or after January 1, 2022.

Antitrust and Competition Laws

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In addition to cleanup actions brought by governmental authorities, private parties could bring personal injury, property damage or other claims due to the presence of, or exposure to, hazardous materials or wastes.

We currently are not party to any claims or any obligations to investigate or remediate any material contamination at any of our facilities.

We currently are not party to any claims or any obligations to investigate or remediate any material contamination at any of our facilities, however, if we were found to be liable under one or more of these laws or regulations, it could create a substantial liability.

We are required to maintain a number of environmental permits and nuclear licenses for our North Billerica, Massachusetts campus, which includes our primary manufacturing, packaging and distribution facility.

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We store low level radioactive waste at our facilities until the materials are below regulatory limits, as allowed by our licenses and permits.

As of December 31, 2022, we currently estimate the D&D cost of all of our manufacturing sites (excluding our Puerto Rico radiopharmacy, which we sold on January 29, 2021) to be approximately $25.1 million.

As of December 31, 2023, we currently estimate the D&D cost of all of our manufacturing sites to be approximately $25.1 million.

As of December 31, 2023 and 2022, we have a liability of approximately $22.9 million and $22.5 million, respectively associated with our asset retirement obligations.

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and (iv) using salt brine as a pretreatment for winter storms to reduce the amount of salt use and run off.

With respect to sustainability, in 2020, we developed a mechanism to track and monitor our energy use, water use and waste generation.

We use an Energy Star Portfolio Manager to track energy and water use that we believe will help us calculate associated greenhouse gas emissions and compare the performance of buildings on our North Billerica campus against a yearly baseline, national medians, and other similar buildings.

We have expanded our tracking and monitoring of energy use, water use and waste generation to include our Somerset, NJ facility.

With respect to sustainability, we track and monitor our energy use, water use, a limited scope of greenhouse gas emissions, and waste generation.

We use an Energy Star Portfolio Manager to track energy and water use and have calculated scope 1 and 2 greenhouse gas emissions for our North Billerica Campus, with plans to expand these activities to other Lantheus properties.

We will continue to compare our usage data against annual baselines, national medians, and similar buildings.

Environmental laws and regulations are complex, change frequently and have become more stringent over time.

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We believe that supporting our local community and instilling a diverse, inclusive, ethical and compliant culture makes us an employer of choice, allows us to maintain good standing with the regulatory authorities and our customers, and benefits our stockholders in the long run.

We have a female Chief Executive Officer, over half of our Vice Presidents and above are women, and approximately 50% of our employees are women.

We continue to strive to improve our diversity and inclusion with a strategic emphasis beyond gender, and we require recruiters working with us to present diversity candidates.

We also sponsor two Employee Resource Groups (“ERGs”), the Lantheus Diversity Connection ERG and the Women Leaders of Lantheus ERG.

We have a female Chief Executive Officer who, effective March 1, 2024, will transition to Chair of the Board, over half of our Vice Presidents and above (including our senior management team, which we refer to as our “Expanded Executive Team”) are women, and approximately 50% of our employees are women.

We continue to strive to improve our diversity and inclusion with a strategic emphasis beyond gender, and we require recruiters working with us to present diverse candidates.

We also sponsor three Employee Resource Groups (“ERGs”), the Lantheus Diversity Connection ERG, the Women Leaders of Lantheus ERG, and the Professional Networking at Lantheus ERG.

We are committed to promoting a culture of ethics and compliance.

11 unchanged sentences

(i) quarterly town hall meetings for our entire company;

(ii) regular ongoing update communications;

(ii) regular ongoing update communications, including through monthly newsletters and our recently launched intranet site;

and (iii) an externally administered whistleblower hotline and website that is prominently advertised to our employees, and a whistleblower’s anonymity is protected, if so requested.

3 unchanged sentences

We work to promote an environment of awareness and shared responsibility for safety and regulatory compliance throughout the Company, in order to minimize risks of injury, exposure, or business impact.

During 2022, we developed “Workplace of the Future” guidelines that were designed to address how workplaces have changed coming out of the COVID-19 pandemic.

The goal of the guidelines was to create a connected and engaged employee environment that balances the need for in-person interaction with the need to be flexible and collaborative across different locations and ways of working.

Corporate History

6 unchanged sentences

We completed our acquisition of Progenics on June 19, 2020 (the “Progenics Acquisition”).

We completed our acquisition of Cerveau Technologies, Inc.

on February 6, 2023 (the “Cerveau Acquisition”).

Our common stock is traded on the NASDAQ Global Market under the symbol “LNTH”.

6 unchanged sentences

iXBRL is an electronic coding language used to create interactive financial statement data over the Internet.

The information on our website is neither part of nor incorporated by reference in this Annual Report on Form 10-K.

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