What changed in this filing

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Item 1. Business

2021-02-25 compared with 2020-02-25 · 484 added, 297 removed, 423 unchanged (65% of the section changed)

We are a global leader in the development, manufacture and commercialization of innovative diagnostic medical imaging agents and products that assist clinicians in the diagnosis and treatment of cardiovascular and other diseases.

Clinicians use our imaging agents and products across a range of imaging modalities, including echocardiography and nuclear imaging.

We believe that the resulting improved diagnostic information enables healthcare providers to better detect and characterize, or rule out, disease, potentially achieving improved patient outcomes, reducing patient risk and limiting overall costs for payers and the entire healthcare system.

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

We sell our products to radiopharmacies, integrated delivery networks, hospitals, clinics and group practices.

We sell our products globally and currently operate our business in two reportable segments, which are further described below:

Segment produces and markets our medical imaging agents and products throughout the U.S.

In the U.S., we primarily sell our products to radiopharmacies, integrated delivery networks, hospitals, clinics and group practices.

International Segment operations consist of production and distribution activities in Puerto Rico and some direct distribution activities in Canada.

Additionally, within our International Segment, we have established and maintain third-party distribution relationships under which our products are marketed and sold in Europe, Canada, Australia, Asia-Pacific and Latin America.

Our Product Portfolio

Our current portfolio of ten commercial products is diversified across a range of imaging modalities.

Our current products include an ultrasound contrast agent and medical radiopharmaceuticals (including Technetium generators).

Ultrasound contrast agents are compounds that are used in diagnostic procedures, such as cardiac ultrasounds or echocardiograms, to improve the clarity of the diagnostic image.

Medical radiopharmaceuticals are radioactive pharmaceuticals used by clinicians to perform nuclear imaging procedures.

In certain circumstances, a radioactive element, or radioisotope, is attached to a chemical compound to form the radiopharmaceutical.

This act of attaching the radioisotope to the chemical compound is called radiolabeling, or labeling.

In other circumstances, a radioisotope can be used as a radiopharmaceutical without attaching any additional chemical compound.

Radioisotopes are most commonly manufactured in a nuclear research reactor, where a target is bombarded with subatomic particles, or in a cyclotron, which is a type of particle accelerator that also creates radioisotopes.

Two common forms of nuclear imaging procedures are single-photon emission computed tomography (“SPECT”) which measures gamma rays emitted by a SPECT radiopharmaceutical, and positron emission tomography (“PET”) which measures positrons emitted by a PET radiopharmaceutical.

As an example of the procedures in which our products may be used, in the diagnosis of cardiovascular disease, a typical diagnostic progression could include an electrocardiogram, followed by an echocardiogram (possibly using our agent DEFINITY) which delineates cardiac structure and function, and then a nuclear myocardial perfusion imaging (“MPI”) study using either SPECT or PET imaging (possibly using our Technetium generator and our Cardiolite SPECT-based MPI agent).

An MPI study assesses blood flow distribution to the heart.

MPI is also used for diagnosing the presence of coronary artery disease.

Progenics Transaction

On October 1, 2019, we entered into an Agreement and Plan of Merger (the “Initial Merger Agreement”) to acquire Progenics Pharmaceuticals, Inc.

PGNX) in an all-stock transaction.

Progenics is an oncology company developing innovative medicines and artificial intelligence to find, fight and follow cancer.

Under the terms of the Initial Merger Agreement, we agreed to acquire all of the issued and outstanding shares of Progenics common stock at a fixed exchange ratio.

Progenics stockholders would have received 0.2502 shares of our common stock for each share of Progenics common stock, representing an approximately 35% aggregate ownership stake in the combined company.

The transaction contemplated by the Initial Merger Agreement was

unanimously approved by the Boards of Directors of both companies and was subject to the terms and conditions set forth in the Initial Merger Agreement, including, among other things, the affirmative vote of a majority of the outstanding shares of common stock of Progenics and a majority of votes cast by the holders of the common stock of the Company.

On February 20, 2020, we entered into an Amended and Restated Agreement and Plan of Merger (the “Amended Merger Agreement”) with Progenics, which amends and restates the Initial Merger Agreement.

Under the terms of the Amended Merger Agreement, we will acquire all of the issued and outstanding shares of Progenics common stock at a fixed exchange ratio whereby Progenics stockholders will receive, for each share of Progenics stock held at the time of the closing of the merger, 0.31 of a share of our common stock, increased from 0.2502 under the Initial Merger Agreement, together with a non-tradeable CVR tied to the financial performance of PyL TM ( 18 F-DCFPyL), Progenics’ prostate-specific membrane antigen targeted imaging agent designed to visualize prostate cancer currently in late stage clinical development (“PyL”).

Each CVR will entitle its holder to receive a pro rata share of aggregate cash payments equal to 40% of U.S.

net sales generated by PyL in 2022 and 2023 in excess of $100 million and $150 million, respectively.

In no event will our aggregate payments under the CVRs exceed 19.9% of the total consideration we pay in the transaction.

As a result of the increase in the exchange ratio, following the completion of the merger, former Progenics stockholders’ aggregate ownership stake will increase to approximately 40% of the combined company from approximately 35% under the Initial Merger Agreement.

Progenics’ stockholders will also now be entitled to appraisal rights as provided under Delaware law.

The transaction contemplated by the Amended Merger Agreement was unanimously approved by the Boards of Directors of both companies and requires, among other things, the affirmative vote of a majority of the outstanding shares of common stock of Progenics and a majority of votes cast by the holders of the common stock of the Company.

In addition, pursuant to the Amended Merger Agreement, the holder of each in-the-money option to purchase shares of Progenics common stock under any equity based compensation plan of Progenics (“Progenics Stock Option”) will be entitled to receive in exchange for each such in-the-money option (i) an option to purchase Lantheus Common Stock (each, a “Lantheus Stock Option”) converted based on the 0.31 exchange ratio, and (ii) a vested or unvested CVR depending on whether the underlying option is vested.

Holders of out-of-the-money Progenics Stock Options will receive Lantheus Stock Options converted on an exchange ratio adjusted based on actual trading prices of common stock of Progenics and Lantheus Holdings prior to the effective time of the merger.

The Amended Merger Agreement also provides that on closing our board of directors will appoint Dr.

Gerard Ber and Mr.

Heinz Mausli, who are currently members of the board of directors of Progenics, to serve on our board of directors.

In addition, our board of directors, subject to complying with applicable fiduciary duties, will use commercially reasonable efforts to cause Dr.

Mausli to be nominated for reelection following the closing through 2023.

Our board of directors will be reduced in size from ten to nine members at our annual meeting of stockholders on April 23, 2020 (or sooner if the transaction closes before then) and will be further reduced in size from nine to eight members prior to the date of our 2021 annual meeting of stockholders.

Except as described above, the material terms of the Amended Merger Agreement are substantially the same as the terms of the Initial Merger Agreement.

The transaction is currently expected to close in the second quarter of 2020.

Upon completion of the acquisition, which the parties intend to report as tax-deferred to Progenics’ stockholders with respect to the stock component of the merger consideration for U.S.

federal income tax purposes, the combined company will continue to be headquartered in North Billerica, Massachusetts and will trade on the NASDAQ under the ticker symbol LNTH.

See our Current Reports on Form 8-K dated October 1, 2019 and February 20, 2020 for further information regarding the Initial Merger Agreement, the Amended Merger Agreement and the proposed Progenics acquisition.

We are an established leader and fully integrated provider of innovative imaging diagnostics, targeted therapeutics, and artificial intelligence solutions to Find, Fight and Follow serious medical conditions.

For our imaging diagnostics, we believe that the resulting improved diagnostic information enables healthcare providers to better detect and characterize, or rule out, disease, potentially achieving improved patient outcomes, reducing patient risk and limiting overall costs for payers and the entire healthcare system.

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

We sell our products to radiopharmacies, PET manufacturing facilities (“PMFs”), integrated delivery networks, hospitals, clinics and group practices.

We sell our products globally and operate our business in two reportable segments, which are further described below:

Segment produces and markets our agents and products throughout the U.S.

In the U.S., we primarily sell to radiopharmacies, PMFs, integrated delivery networks, hospitals, clinics and group practices.

• International Segment operations consist of direct distribution in Canada and Puerto Rico, as well as third-party distribution relationships in Europe, Canada, Australia, Asia-Pacific and Latin America and our EXINI business in Sweden.

We are in the process of evaluating our operating and reporting structure.

We anticipate this evaluation, which we expect to complete during 2021, may result in a change to our existing operating segment reporting structure.

Progenics Acquisition

On June 19, 2020, we completed the Progenics Acquisition.

Progenics is an oncology company focused on developing and commercializing innovative targeted medicines and artificial intelligence to Find, Fight and Follow cancer.

Progenics’ portfolio of products and product candidates includes, among other things, therapeutic agents designed to target cancer (AZEDRA, 1095 and PSMA TTC), diagnostic imaging agents designed to target PSMA for prostate cancer (PyL and 1404), RELISTOR for opioid-induced constipation (“OIC”), artificial intelligence (“AI”) imaging technologies and leronlimab being developed for HIV infection and COVID-19 applications.

Progenics’ current revenue is generated from two principal sources:

first, royalties, development and commercial milestones from strategic partnerships, including royalties from Bausch from sales of RELISTOR;

and second, AZEDRA sales.

Lantheus Holdings issued 26,844,877 shares of Lantheus Holdings common stock and 86,630,633 CVRs to former Progenics stockholders in connection with the Progenics Acquisition.

Lantheus Holdings also assumed 34,000 in-the-money Progenics stock options and 6,507,342 out-of-the-money Progenics stock options, each converted into Replacement Stock Options at an exchange ratio of 0.31.

As a result of the Progenics Acquisition, we added the following products and product candidates to our portfolio:

Product / Product Candidate

Ultra-Orphan Therapeutic

AZEDRA (iobenguane I 131) 555 MBq/mL injection

Unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma

Prostate Cancer Diagnostics and Therapeutics

PyL (18F-DCFPyL)

PSMA-targeted PET/CT imaging agent for prostate cancer

NDA accepted;

PDUFA date of May 28, 2021

Worldwide (ex.

PyL (18F-DCFPyL)

PSMA-targeted PET/CT imaging agent for prostate cancer

Late stage development

1095 (I 131 1095)

PSMA-targeted small molecule therapeutic for metastatic prostate cancer

PSMA TTC (BAY 2315497)

PSMA-targeted antibody conjugate therapeutic for metastatic prostate cancer

Technetium-99m PSMA-targeted SPECT/CT imaging agent for prostate cancer

Discussions with European Medicines Agency (EMA)

Digital Solutions

AI-based imaging analysis technology that assists readers in quantification and standardized reporting of PSMA-targeted PET/CT imaging, providing an objective understanding of disease status Investigational Use Only

Automated Bone Scan Index (aBSI)

Automated reading and quantification of bone scans of prostate cancer patients using AI and deep learning

Approved in the U.S.

(510(k) clearance) and in the E.U.

Automated Bone Scan Index (BONENAVI)

Automated reading and quantification of bone scans of prostate cancer patients using AI and deep learning

Approved in Japan

Other Partnerships

RELISTOR Subcutaneous Injection (methylnaltrexone bromide)

OIC in adults with chronic non-cancer pain or advanced-illness adult patients

RELISTOR Tablets (methylnaltrexone bromide)

OIC in adults with chronic non-cancer pain

leronlimab (PRO 140)

HIV Infection, COVID-19

CytoDyn is working to provide information required by the FDA in order to resubmit a BLA for HIV;

CytoDyn has started recruiting for a Phase 2b/3 trial for COVID-19

See Part I, Item 1A.

“Risk Factors” for information regarding certain risks associated with our proposed acquisition of Progenics.

DEFINITY and the Expansion of Our Ultrasound Microbubble Franchise

DEFINITY is the leading ultrasound contrast imaging agent based on revenue and usage in the U.S., and is indicated for use in patients with suboptimal echocardiograms.

“Risk Factors” in this Annual Report on form 10-K for the year ended December 31, 2020, for information regarding certain risks associated with our Progenics Acquisition.

Our Portfolio of Commercial Products

Our commercial products now include the following:

• DEFINITY is a microbubble ultrasound enhancing agent used in ultrasound exams of the heart, also known as echocardiography exams.

DEFINITY contains perflutren-containing lipid microspheres and is indicated in the U.S.

for use in patients with suboptimal echocardiograms to assist in imaging the left ventricular chamber and left endocardial border of the heart in ultrasound procedures.

In November 2020, the FDA approved our supplemental new drug application (“sNDA”) for DEFINITY RT.

DEFINITY RT is a modified formulation of DEFINITY that allows both storage and shipment at room temperature (DEFINITY’s previously approved formulation requires refrigerated storage).

We believe we are currently the leading provider of ultrasound microbubble enhancing agents in the world.

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

TechneLite uses Mo-99 as its active ingredient.

• NEUROLITE is an injectable, Tc-99m-labeled imaging agent used with SPECT technology to identify the area within the brain where blood flow has been blocked or reduced due to stroke.

• RELISTOR (methylnaltrexone bromide) is a treatment for OIC that decreases the constipating side effects induced by opioid pain medications such as morphine and codeine without diminishing their ability to relieve pain.

RELISTOR is approved in two forms:

a subcutaneous injection and an oral tablet.

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

Our Xenon is manufactured by a third party as a bi-product of Mo-99 production and is processed and finished by us.

We believe we are currently the leading provider of Xenon in the U.S.

• 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.

• Gallium-67 (“Gallium”) is an injectable radiopharmaceutical imaging agent used to detect certain infections and cancerous tumors, especially lymphoma.

We manufacture Gallium using cyclotron technology.

• Thallium-201 (“Thallium”) is an injectable radiopharmaceutical imaging agent used in MPI studies to detect cardiovascular disease.

We manufacture Thallium using cyclotron technology.

• AZEDRA (iobenguane I 131) is a radiotherapeutic, approved for the treatment of adult and pediatric 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.

• QUADRAMET is an injectable radiopharmaceutical used to treat severe bone pain associated with osteoblastic metastatic bone lesions.

We serve as the direct manufacturer and supplier of QUADRAMET in the U.S.

• Automated Bone Scan Index (“aBSI”) calculates the disease burden of prostate cancer by quantifying the hotspots on bone scans and automatically calculating the bone scan index value, representing the disease burden of prostate cancer shown on the bone scan.

This quantifiable and reproducible calculation of the bone scan index value is intended to aid in the diagnosis and treatment of men with prostate cancer and may have utility in monitoring the course of the disease.

The Japanese rights to the stand-alone aBSI have been transferred and sold to FUJIFILM Toyama Chemical Co.

(“FUJIFILM”) under the name BONENAVI ® .

The cloud based aBSI was made available for clinical use in the U.S.

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 September 2020, the FDA granted 510(k) clearance for the use of aBSI on a GE Healthcare system.

• Cobalt (Co 57) is a non-pharmaceutical radiochemical used in the manufacture of sources for the calibration and maintenance of SPECT imaging cameras.

Sales of our microbubble ultrasound enhancing agent, DEFINITY, are made in the U.S.

and Canada through a DEFINITY direct sales team.

In the U.S., our nuclear imaging products, including TechneLite, Xenon, NEUROLITE and Cardiolite, are primarily distributed through commercial radiopharmacies, the majority of which are controlled by or associated with Cardinal, RLS (previously GE Healthcare), UPPI, Jubilant Radiopharma and PharmaLogic.

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

are made through our direct sales force to hospitals and clinics that maintain their own in-house radiopharmaceutical preparation capabilities.

AZEDRA is also sold in the U.S.

through an AZEDRA direct sales team.

RELISTOR was licensed to Bausch, and we collect quarterly royalties based on those sales.

We also maintain our own direct sales force in Canada for certain of our products.

In Europe, Australia, Asia-Pacific and Latin America, we generally rely on third-party distributors to market, sell and distribute our nuclear imaging and ultrasound enhancing agent products, either on a country-by-country basis or on a multi-country regional basis.

Our headquarters are located in North Billerica, MA with offices in New York, NY;

Somerset, NJ;

Montreal, Canada and Lund, Sweden.

Anticipated continued growth of DEFINITY and Expansion of Our Ultrasound Microbubble Franchise

DEFINITY is the leading ultrasound enhancing agent based on revenue and usage in the U.S., and is indicated for use in patients with suboptimal echocardiograms.

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

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Better visualization of the left ventricle allows clinicians to make more informed decisions about disease status.

DEFINITY offers flexible dosing and administration through an IV bolus or diluted bolus injection or continuous IV infusion.

We believe DEFINITY’s synthetic lipid-cased coating gives the agent a distinct competitive advantage, because it provides a strong ultrasound signal and is the only perflutren-based echo contrast agent made without albumin.

There were approximately 31.5 million echocardiograms performed in the U.S.

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Assuming 20% of echocardiograms produce suboptimal images, as stated in the clinical literature, we estimate that approximately 6.3 million echocardiograms in 2020 produced suboptimal images.

The use of DEFINITY during echocardiography allows physicians to significantly improve their assessment of the function of the left ventricle.

In 2019, a year in which the volume of echocardiograms was not impacted by the COVID-19 pandemic, there were 35.1 million echocardiograms performed in the U.S.

according to a third party source.

Assuming the same 20% of suboptimal images, we estimate that approximately 7.0 million echocardiograms in 2019 produced suboptimal images.

Since its launch in 2001, DEFINITY has been used in imaging procedures in more than 16.1 million studies throughout the world.

We estimate that DEFINITY had over 80% share of the U.S.

segment for contrast agents in echocardiography procedures as of December 2019 .

DEFINITY currently competes with Optison, a GE Healthcare product, Lumason, a Bracco product (known as SonoVue outside the U.S.) as well as echocardiography without contrast and non-echocardiography imaging modalities.

segment for ultrasound enhancing agents in echocardiography procedures as of December 2020.

DEFINITY currently competes with Optison, a GE Healthcare product, Lumason, a Bracco product (known as SonoVue outside the U.S.) as well as echocardiography without ultrasound enhancing agents and non-echocardiography imaging modalities.

DEFINITY, Optison and Lumason 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.

“Risk Factors- Ultrasound contrast agents may cause side effects which could limit our ability to sell DEFINITY .”

As we continue to pursue expanding our micro bubble franchise, our activities include:

Patents - We continue to actively pursue additional patents in connection with DEFINITY, both in the U.S.

“Risk Factors-Ultrasound enhancing agents may cause side effects which could limit our ability to sell DEFINITY.”

As we continue to pursue expanding our microbubble franchise, our activities include:

• Patents - We continue to actively pursue additional patents in connection with DEFINITY and DEFINITY RT, both in the U.S.

and internationally.

In the U.S., we have an Orange Book-listed method of use patent expiring in March 2037 and additional manufacturing patents that are not Orange Book-listed expiring in 2021, 2023 and 2037.

Outside of the U.S., while our DEFINITY patent protection and regulatory exclusivity have generally expired, we are currently prosecuting additional patent applications to try to obtain similar method of use and manufacturing patent protection as granted in the U.S.

for DEFINITY we now own a total of four Orange Book-listed method of use patents, one of which expires in 2035 and three of which expire in 2037, as well as additional manufacturing patents that are not Orange Book-listed expiring in 2021, 2023 and 2037.

for DEFINITY RT, we own a total of five Orange Book-listed patents, including a composition of matter patent which expires in 2035.

Outside of the U.S., while our original DEFINITY patent protection and regulatory exclusivity have generally expired, we are currently prosecuting 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 which expires in 2037;

additional VIALMIX RFID patent applications have been submitted in major markets throughout the world.

• Hatch-Waxman Act - 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) the marketing of that generic candidate does not infringe an Orange Book-listed patent.

With respect to any Orange Book-listed patent covering the innovator product, the ANDA applicant must give a notice to the innovator (a “Notice”) that the ANDA applicant certifies that its generic candidate will not infringe the innovator’s Orange Book-listed patent or that the Orange Book-listed patent is invalid.

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

If we were to (i) receive any such Notice in the future, (ii) bring a patent infringement suit against the ANDA applicant within 45 days of receiving that Notice, and (iii) successfully obtain the full 30 month stay, then the ANDA applicant would be precluded from commercializing a generic version of DEFINITY prior to the expiration of that 30 month stay period and, potentially, thereafter, depending on how the patent dispute is resolved.

precluded from commercializing a generic version of DEFINITY prior to the expiration of that 30 month stay period and, potentially, thereafter, depending on how the patent dispute is resolved.

Solely by way of example and not based on any knowledge we currently have, if we received a Notice from an ANDA applicant in March 2021 and the full 30 month stay was obtained, then the ANDA applicant would be precluded from commercialization until at least September 2023.

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

Modified Formulation - We are developing at SBL a modified formulation of DEFINITY.

We believe this modified formulation will provide an enhanced product profile enabling storage as well as shipment at room temperature (DEFINITY’s current formulation requires refrigerated storage), will give clinicians additional choice, and will allow for greater utility of this formulation in broader clinical settings.

We have a composition of matter patent on the modified formulation which runs through December 2035.

If the modified formulation is approved by the FDA, then this patent would be eligible to be listed in the Orange Book.

We currently believe that, if approved by the FDA, the modified formulation could become commercially available in early 2021, although that timing cannot be assured.

Given its physical characteristics, the modified formulation may also be better suited for inclusion in kits requiring microbubbles for other indications and applications (including in kits developed by third parties of the type described in the next paragraph).

New Clinical Applications - As we continue to look for other opportunities to expand our microbubble franchise, we are evaluating new indications and clinical applications beyond echocardiography and contrast imaging generally.

For example, we recently announced a strategic development and commercial collaboration with Cerevast Medical, Inc.

(“Cerevast”) in which our microbubble will be used in connection with Cerevast’s ocular ultrasound device to target improving blood flow in occluded retinal veins in the eye.

• DEFINITY RT - In November 2020, the FDA approved our sNDA for DEFINITY RT.

DEFINITY RT is a modified formulation of DEFINITY that allows both storage and shipment at room temperature (DEFINITY’s previously approved formulation requires refrigerated storage).

The modified formulation provides clinicians an additional choice and allows for greater utility of this formulation in broader clinical settings.

We believe DEFINITY RT will become commercially available later in 2021, although that timing cannot be assured.

Given its physical characteristics, we believe DEFINITY RT is also well-suited for inclusion in kits requiring microbubbles for other indications and applications (including in kits developed by third parties of the type described in the paragraph entitled New Clinical Applications below).

• VIALMIX RFID – In August 2020, we announced the FDA approved our sNDA for our next-generation activation device designed specifically for both DEFINITY and DEFINITY RT.

The activation rate and time are controlled by VIALMIX RFID through the use of radio-frequency identification technology (“RFID”) to ensure reproducible activation of DEFINITY and DEFINITY RT.

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

• New Clinical Applications - As we continue to look for other opportunities to expand our microbubble franchise, we are evaluating new indications and clinical applications beyond echocardiography and ultrasound enhancing agent imaging generally.

• In April 2019, we announced a strategic development and commercial collaboration with Cerevast Medical, Inc.

(“Cerevast”) in which our microbubbles will be used in connection with Cerevast’s ocular ultrasound device to improve blood flow in occluded retinal veins in the eye.

Retinal vein occlusion is one of the most common causes of vision loss worldwide.

Glioblastoma is a lethal and devasting from of brain cancer with median survival of 15 months after diagnosis.

In-House Manufacturing - We are currently building specialized in-house manufacturing capabilities at our North Billerica, Massachusetts facility for DEFINITY and, potentially, other sterile vial products.

• In December 2019, we announced a strategic commercial supply agreement with CarThera for the use of our microbubbles in combination with SonoCloud, a proprietary implantable device in development for the treatment of recurrent glioblastoma.

Glioblastoma is a lethal and devastating form of brain cancer with median survival of 15 months after diagnosis.

• In October 2020, we announced a strategic collaboration with Insightec Ltd.

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

• In-House Manufacturing - We have completed construction of specialized, in-house manufacturing capabilities at our North Billerica, Massachusetts facility for DEFINITY and, potentially, other sterile vial products.

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

We currently expect to be in a position to use this in-house manufacturing capability by early 2021, although that timing cannot be assured.

As part of our microbubble franchise strategy, we also conducted two Phase 3, open-label, multicenter studies to evaluate left ventricular ejection fraction (“LVEF”) measurement accuracy and reproducibility of DEFINITY contrast-enhanced and unenhanced echocardiography as compared to non-contrast cardiac magnetic resonance imaging (“CMRI”) used as the truth standard.

The first of the two trials, BENEFIT 1, enrolled 145 subjects.

After reviewing the study results from BENEFIT 1, we concluded there was no statistically significant improvement in the accuracy of LVEF values for contrast-enhanced echocardiography versus unenhanced echocardiography as compared to CMRI.

In addition, analyses of the secondary endpoints revealed no improvement in inter-reader variability between the contrast-enhanced and unenhanced echocardiograms for LVEF assessments.

A post-hoc analysis, however, did show statistically significant improvements in left ventricular diastolic, systolic and stroke volume measurements with contrast-enhanced versus unenhanced echocardiography when compared to CMRI.

We will continue to analyze the BENEFIT 1 data, and when the data from BENEFIT 2 are available, we will compile the data sets to analyze the full results of the trials.

We currently expect to make use of this in-house manufacturing capability in late 2021, although that timing cannot be assured.

• DEFINITY in China - In March 2020 in connection with our Chinese development and distribution arrangement with Double-Crane Pharmaceutical Company (“Double-Crane”), we filed an Import Drug License application with the National Medical Products Administration, or the NMPA, for the use of DEFINITY for the echocardiography indication.

We believe this is an important milestone in our efforts to commercialize DEFINITY in China.

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

See Part I, Item 1A.

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See “Raw Materials and Supply Relationships—Molybdenum-99” below.

TechneLite is produced in 13 sizes (based on amount of radioactivity) and is currently marketed primarily in North America and Latin 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 the significant radiopharmacy groups, including GE Healthcare, Cardinal, UPPI, Jubilant Radiopharma and PharmaLogic.

TechneLite is currently marketed primarily in North America and Latin 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 the significant radiopharmacy groups, including Cardinal, RLS, UPPI, Jubilant Radiopharma and PharmaLogic.

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

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generator market as of December 31, 2020, competing primarily with Tc-99m-based generators produced by Curium.

In Puerto Rico, we also supply TechneLite to our wholly-owned radiopharmacy to prepare radiopharmaceutical imaging agent unit doses.

In Canada, we have a supply agreement (the “Isologic Supply Agreement”) with Isologic Innovative Radiopharmaceuticals Ltd.

(“Isologic”).

Under the Isologic Supply Agreement, we supply Isologic with certain of our products on commercial terms, including certain product purchase commitments by Isologic.

The agreement expires in January 2021 and may be terminated upon the occurrence of specified events, including a material breach by the other party, bankruptcy by either party or certain force majeure events.

In Australia, we have a supply agreement (the “GMS Supply Agreement”) with Global Medical Solutions (“GMS”).

Under the GMS Supply Agreement, we supply GMS with certain of our products on commercial terms, including certain minimum product purchase commitments by GMS.

The agreement expires in August 2020 and may be terminated in whole or in part on a product-by-product basis upon the occurrence of specified events, including a material breach by the other party, bankruptcy by either party or certain force majeure events.

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

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.

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TechneLite has patent protection in the U.S.

and various foreign countries on certain component technology currently expiring in 2029.

and various foreign countries on certain component technology currently expiring in 2029, and we are pursuing additional patent protection in the U.S.

and world-wide on other component technology that, if granted, would expire in 2040.

In addition, given the 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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“Management’s Discussion and Analysis of Financial Condition and Results of Operations-Comparison of the Periods Ended December 31, 2020 and 2019-Revenues” for further information on total revenue contributed by TechneLite in each of our last three fiscal years.

Other Commercial Products

In addition to the products listed above, our portfolio of commercial products also includes important imaging agents in specific segments, which provide a stable base of recurring revenue.

Most of these products have a favorable industry position as a result of our substantial infrastructure investment, specialized workforce, technical know-how and supplier and customer relationships.

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

Our Xenon is manufactured by a third party as a bi-product of Mo-99 production and is processed and finished by us.

We are currently the leading provider of Xenon in the U.S.

Neurolite is an injectable, Tc-99m-labeled imaging agent used with SPECT technology to identify the area within the brain where blood flow has been blocked or reduced due to stroke.

We launched Neurolite in 1995.

Cardiolite , also known by its generic name sestamibi, is an injectable, Tc-99m-labeled imaging agent used in 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.

Thallium TI 201 is an injectable radiopharmaceutical imaging agent used in MPI studies to detect cardiovascular disease.

We have marketed Thallium since 1977 and manufacture the agent using cyclotron technology.

FDG is an injectable, fluorine-18-radiolabeled imaging agent used with PET technology to identify and characterize tumors in patients undergoing oncologic diagnostic procedures.

We manufacture and distribute FDG from our Puerto Rico radiopharmacy.

Gallium (Ga 67) is an injectable radiopharmaceutical imaging agent used to detect certain infections and cancerous tumors, especially lymphoma.

We manufacture Gallium using cyclotron technology.

Quadramet , currently our only therapeutic product, is an injectable radiopharmaceutical used to treat severe bone pain associated with osteoblastic metastatic bone lesions.

We serve as the direct manufacturer and supplier of Quadramet in the U.S.

Cobalt (Co 57) is a non-pharmaceutical radiochemical used in the manufacture of sources for the calibration and maintenance of SPECT imaging cameras.

Our Portfolio of Clinical Development Candidates

In addition to our commercial products, we now have an extensive portfolio of product candidates in clinical development, including:

• PyL (also known as 18F-DCFPyL) is a fluorine 18-based PSMA-targeted PET imaging agent that enables visualization of primary tumors as well as bone and soft tissue metastases, with potential high clinical utility in the detection of recurrent and/or metastatic prostate cancer.

Progenics has completed a clinical development program that consisted of two pivotal clinical studies, which were designed to provide robust, prospective, well-controlled, and pathology- or composite truth standard-verified data to establish the safety and diagnostic performance of PyL across the disease continuum of prostate cancer.

results from these studies provide data in support of the potential of PyL to reliably detect and localize disease, including in patients with low PSA values, and may help enable appropriate disease management, thus supporting the potential use for detection of recurrent or metastatic prostate cancer.

We filed the PyL NDA with the FDA in September 2020 and received notice of priority review in December 2020 with a PDUFA date of May 28, 2021.

• flurpiridaz F 18 is a fluorine 18-based PET MPI agent designed to assess blood flow to the heart in patients suspected of coronary artery disease (CAD).

In April 2017, we announced entering into a definitive, exclusive Collaboration and License Agreement with GE Healthcare for the agent’s continued Phase 3 development and worldwide commercialization.

The second Phase 3 trial is now underway;

however, because of the COVID-19 pandemic, enrollment in the global clinical development program had been delayed and has now resumed at a slower recruiting pace.

GE Healthcare now expects to complete enrollment in the second half of 2021 and, assuming regulatory approval, begin commercialization in early 2023.

• 1095 (also known as I-131-1095) 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.

Progenics initiated eleven clinical sites in the U.S.

along with the six active sites in Canada to support enrollment in the Company’s multicenter, randomized, controlled, ARROW Phase 2 study in mCRPC.

Because of the COVID-19 pandemic, Progenics new enrollment in the Phase 2 trial was paused to minimize the risk to subjects and healthcare providers during the pandemic.

Subjects who were active and had been randomized for the study continued to receive treatment doses and were monitored for safety and efficacy in a manner that is permissible by each clinical site.

New enrollment in the ARROW Phase 2 study restarted in October 2020.

• LMI 1195 is a fluorine 18-based PET imaging agent for the norepinephrine pathway.

We have designed but not yet commenced two Phase 3 clinical trials for the use of LMI 1195 for the diagnosis and management of neuroendocrine tumors in pediatric and adult populations, respectively.

The FDA has granted an Orphan Drug designation for the use of LMI 1195 in the management indication.

We have also received notice of eligibility for a rare pediatric disease priority review voucher for a subsequent human drug application so long as LMI 1195 is approved by the FDA for its rare pediatric disease indication.

Pursuant to federal legislation passed and signed into law in late 2020, the expiration date of the rare pediatric disease priority review voucher program was extended from September 30, 2022 to September 30, 2026.

• PSMA TTC is a thorium-227 labeled PSMA-targeted antibody therapeutic.

PSMA TTC is designed to deliver a dose of alpha radiation directly to prostate cancer cells with minimal impact on the surrounding healthy tissues.

Bayer AG (“Bayer”) has exclusive worldwide rights to develop and commercialize products using our PSMA antibody platform in combination with Bayer’s alpha-emitting radionuclides.

Bayer is conducting a Phase 1 trial of PSMA TTC in subjects with metastatic castration-resistant prostate cancer (“mCRPC”).

• 1404 is a Tc-99m labeled small molecule which binds to PSMA and is used as a SPECT/CT imaging agent to diagnose and detect localized prostate cancer as well as soft tissue and bone metastases.

ROTOP has exclusive rights to develop, manufacture and commercialize 1404 in Europe.

• PSMA-AI is an AI-based imaging analysis technology that assists readers in quantification and standardized reporting of PSMA-targeted PET/CT imaging, providing an objective understanding of disease status.

The technology automatically analyzes the CT image to segment anatomical regions – 51 bones and 12 soft tissue organs.

This CT segmentation enables automated localization, detection and quantification of potential PSMA-avid lesions in the PET image, which is incorporated into a standardized report for physicians.

In a recent study, the technology demonstrated better consistency in quantitative assessment across multiple readers and high sensitivity (>90%) in detecting potential lesions in PSMA PET/CT.

The clinical utility of the device is being investigated in multiple outcome-based studies.

• leronlimab (PRO 140) is an investigational humanized monoclonal antibody targeting the CCR5 receptor.

CCR5 appears to act as an HIV entry inhibitor and may play a broader role in tumor metastasis and immune-mediated illnesses.

It is owned by CytoDyn Inc.

(“CytoDyn”) pursuant to our agreement with CytoDyn, as described below.

In May 2020, CytoDyn announced it submitted a Biologics License Application (“BLA”) to the FDA for approval of leronlimab in combination therapy for HIV infection.

On July 13, 2020, CytoDyn announced that it had received a refusal to file letter from the FDA for the BLA.

In August and September 2020, the FDA provided written responses to CytoDyn’s questions and met telephonically with CytoDyn key personnel and its clinical research organization concerning its recent BLA for this HIV combination therapy to expedite the resubmission of its BLA filing for this indication.

CytoDyn is working diligently to resubmit the BLA, which it expects to file in the first half of calendar year 2021.

Leronlimab is also being evaluated by CytoDyn for patients with mild/moderate COVID-19 indications in a Phase 2 randomized clinical trial that was recently completed.

Also, CytoDyn has started recruiting for a Phase 2b/3 trial for 390 severe or critical COVID-19 patients.

For the years ended December 31, 2020, 2019 and 2018, we invested $32.8 million, $20.0 million and $17.1 million in research and development (“R&D”), respectively.

Our R&D team includes our Medical Affairs and Medical Information functions, which educate physicians on the scientific aspects of our commercial products and the approved indications.

See Part I, Item 1A.

“Risk Factors” for information regarding certain risks associated with our clinical development programs.

Strategic Partnerships

In connection with our commercial products and product candidates, we now have a number of strategic partnerships, including:

• 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.

net sales targets, including:

Net Sales Levels in any Single Calendar Year

(In thousands)

In excess of $150 million

In excess of $200 million

In excess of $300 million

In excess of $750 million

In excess of $1 billion

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.

• GE Healthcare Agreement – Under our April 2017 Collaboration and License Agreement, GE Healthcare will complete the worldwide development of flurpiridaz F 18, 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 the right to co-promote the agent in the U.S.

GE Healthcare’s development plan initially focuses on obtaining regulatory approval in the U.S., Japan, Europe and Canada.

Under the agreement, we received an upfront cash payment of $5.0 million and are eligible to receive up to $60.0 million in regulatory and sales milestone payments, tiered double-digit royalties on U.S.

sales, and mid-single digit royalties on sales outside of the U.S.

• Curium Agreement – Curium has licensed exclusive rights to develop and commercialize PyL in Europe.

Under the terms of the collaboration, Curium is responsible for the development, regulatory approvals and commercialization of PyL in Europe, and we are entitled to double-digit royalties on net sales of PyL.

Curium is currently in late-stage development in Europe.

• Bayer Agreements – Under Progenics’ April 2016 agreement with a subsidiary of Bayer granting Bayer exclusive worldwide rights to develop and commercialize products using our PSMA antibody platform, in combination with Bayer’s alpha-emitting radionuclides, Progenics received an upfront payment of $4.0 million and milestone payments totaling $5.0 million.

We could receive up to an additional $44.0 million in potential clinical and development milestones.

We are also entitled to single-digit royalties on net sales, and potential net sales milestone payments up to an aggregate of $130.0 million.

In addition, in October 2020, we entered into a PyL Clinical Supply Agreement with Bayer to include PyL in their clinical trial for prostate cancer.

PyL will be used by Bayer to assess PSMA expression levels at baseline and during treatment.

• CytoDyn Agreement -- Progenics sold leronlimab to CytoDyn in 2012, which sale included milestone and royalty payment obligations to Progenics.

Under the 2012 agreement, CytoDyn is responsible for all development, manufacturing and commercialization efforts.

Pursuant to such agreement, Progenics received $5.0 million in upfront and milestone payments, and we have the right to receive an additional $5.0 million upon the first U.S.

approval for the sale of the drug, and a 5% royalty on the net sales of approved products.

• ROTOP Agreement -- In May 2019, Progenics entered into an exclusive license agreement with ROTOP, a Germany-based developer of radiopharmaceuticals for nuclear medicine diagnostics, to develop, manufacture and commercialize 1404 in Europe.

Under the terms of the collaboration, ROTOP is responsible for the development, regulatory approvals and

commercialization of 1404 in Europe while we are entitled to double-digit, tiered royalties on net sales of 1404 in Europe.

ROTOP is in discussions with EMA regarding the development path in Europe.

• FUJIFILM Agreement -- In June 2019, EXINI entered into a transfer agreement with FUJIFILM for the rights to the bone scan index product in Japan for use under the name BONENAVI.

Under the terms of the transfer agreement, FUJIFILM acquired, by a combination of purchase and license, the Japanese software, source code, supporting data and all Japanese patents associated with the bone scan index product from EXINI for use in Japan.

In exchange, EXINI received $4.0 million in an upfront payment and FUJIFILM agreed to pay EXINI support and service fees for bone scan index and other AI products over the next three years in Japan.

BONENAVI has been licensed to FUJIFILM for use in Japan since 2011.

In February 2021, EXINI entered into a new agreement with FUJIFILM for the heart myocardial perfusion analysis software, cREPO, in Japan.

• Regeneron Agreement – In June 2020, we entered into a PyL Clinical Supply Agreement with Regeneron Pharmaceuticals, Inc.

(“Regeneron”) under which we will supply PyL to Regeneron as an imaging agent to evaluate and follow subjects for a Phase 1/2 clinical study of Regeneron’s PSMA-targeted mCRPC therapeutic candidate.

• POINT Biopharma – In December 2020, we entered into a PyL Clinical Supply Agreement with POINT Biopharma US Inc.

(“POINT Biopharma”) under which we will supply PyL to POINT Biopharma as an imaging agent to evaluate and follow subjects for a Phase 3 clinical study of POINT Biopharma’s PSMA-targeted mCRPC therapeutic candidate.

Distribution, Marketing and Sales

The following table sets forth certain key market information for each of our commercial pharmaceutical products:

Approved Markets

Australia, Canada, European Union, European Economic Area, India, Israel, Mexico, New Zealand, Singapore, South Korea, Taiwan, United States

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

Canada, United States

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

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

Thallium Tl 201

Australia, Canada, Colombia, New Zealand, Pakistan, Panama, South Korea, Taiwan, United States

Gallium Ga 67

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

United States

and Canada, we have a sales team of approximately 80 employees that call on healthcare providers in the echocardiography space, as well as radiopharmacy chains, integrated delivery networks and group purchasing organizations.

Our radiopharmaceutical products are sold in the U.S.

through a subset of our sales team, primarily to radiopharmacies.

Product Approved Markets

DEFINITY Australia, Canada, European Union, European Economic Area, India, Israel, Mexico, New Zealand, Singapore, South Korea, Taiwan, 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

RELISTOR (Solution for Injection 12 mg/0.6 mL vial) Austria, Belgium, Bulgaria, Canada, Switzerland, Cypress, Czechia, Germany, Denmark, Estonia, Greece, Spain, Finland, France, Croatia, Hungary, Ireland, Iceland, Italy, Liechtenstein, Lithuania, Luxembourg, Latvia, Malta, Netherlands, Norway, Poland, Portugal, Romania, Sweden, Slovenia, Slovakia, United Kingdom, United States

RELISTOR (Solution for Injection in pre-filled syringe 8mg and pre-filled syringe 12 mg) Austria, Belgium, Bulgaria, Canada, Cypress, Czechia, Germany, Denmark, Estonia, Greece, Spain, Finland, France, Croatia, Hungary, Ireland, Iceland, Italy, Liechtenstein, Lithuania, Luxembourg, Latvia, Malta, Netherlands, Norway, Poland, Portugal, Romania, Sweden, Slovenia, Slovakia, United Kingdom, United States

RELISTOR (methylnaltrexone bromide) Oral Tablet 140 mg 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

Gallium Australia, Canada, Colombia, Costa Rica, New Zealand, Pakistan, Panama, South Korea, Taiwan, United States

Thallium Australia, Canada, Colombia, New Zealand, Pakistan, Panama, South Korea, Taiwan, United States

AZEDRA United States

QUADRAMET United States

and Canada, our sales team of approximately 80 employees is split into separate sales teams for each of DEFINITY, AZEDRA and our radiopharmaceutical products.

We are also beginning to assemble a sales and commercial team for PyL in anticipation of potential FDA approval and a commercial launch later in 2021.

We sell a majority of our radiopharmaceutical products in the U.S.

to five radiopharmacy groups—namely GE Healthcare, Cardinal, UPPI, Jubilant Radiopharma and PharmaLogic.

to five radiopharmacy groups—namely Cardinal, RLS, UPPI, Jubilant Radiopharma and PharmaLogic.

Our contractual distribution and other arrangements with these radiopharmacy groups are as follows:

GE Healthcare maintains approximately 31 radiopharmacies in the U.S.

that purchase our TechneLite generators.

We estimate that GE Healthcare distributed approximately 9% of the aggregate U.S.

SPECT doses sold in the first half of 2019 .

We currently have an agreement with GE Healthcare for the distribution of TechneLite, Xenon and other products.

The agreement provides that GE Healthcare will purchase a minimum percentage of TechneLite generators as well as certain other products from us.

Our agreement, which expires on December 31, 2020 , may be terminated by either party upon the occurrence of specified events including a material breach by either party, bankruptcy by either party, certain irresolvable regulatory changes or economic circumstances, or force majeure events.

• Cardinal maintains approximately 131 radiopharmacies that are typically located in large, densely populated urban areas in the U.S.

We estimate that Cardinal’s radiopharmacies distributed approximately 44% of the aggregate U.S.

SPECT doses sold in the first half of 2019 (the latest information currently available to us).

Our written supply agreement with Cardinal relating to TechneLite, Xenon, Neurolite and other products expires on December 31, 2020 .

SPECT doses sold in the first half of 2020.

Our supply agreement with Cardinal relating to TechneLite, Xenon, NEUROLITE and other products has been extended until December 31, 2022.

The agreement specifies pricing levels and requirements to purchase minimum percentages of certain products during certain periods.

The agreement may be terminated upon the occurrence of specified events, including a material breach by the other party and certain force majeure events.

• RLS maintains approximately 31 radiopharmacies in the U.S.

that purchase our TechneLite generators.

RLS purchased these radiopharmacies from GE Healthcare in the third quarter of 2020.

We estimate that RLS distributed approximately 8% of the aggregate U.S.

SPECT doses sold in the first half of 2020.

We currently have an agreement with RLS for the distribution of TechneLite, Xenon and Gallium.

The agreement provides that RLS will purchase a minimum percentage of TechneLite generators as well as certain other products from us.

Our agreement, which has been extended until December 31, 2021, may be terminated by either party upon the occurrence of specified events including a material breach by either party, bankruptcy by either party, certain irresolvable regulatory changes or economic circumstances, or force majeure events.

• UPPI is a cooperative purchasing group (roughly analogous to a group purchasing organization) of approximately 52 independently owned or smaller chain radiopharmacies located in the U.S.

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We are entitled to terminate the UPPI agreement upon 60 days written notice.

The UPPI agreement expires on December 31, 2020 .

The UPPI agreement has been extended until December 31, 2023.

• Jubilant Radiopharma maintains approximately 48 radiopharmacies in the U.S.

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The agreement specifies pricing levels and volume and percentage purchase requirements.

The agreement will expire on December 31, 2020 and may be terminated upon the occurrence of specified events, including a material breach by the other party.

The agreement has been extended until June 30, 2021 and may be terminated upon the occurrence of specified events, including a material breach by the other party.

• PharmaLogic maintains approximately 27 radiopharmacies in the U.S.

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SPECT doses sold in the first half of 2020.

Our written supply agreement with PharmaLogic relating to TechneLite, Xenon, Cardiolite and other products expires on December 31, 2020.

Our written supply agreement with PharmaLogic relating to TechneLite, Xenon, Cardiolite and other products has been extended until December 31, 2021.

The agreement specifies pricing levels and requirements to purchase minimum percentages of certain products during certain periods.

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In the latter case, this represents a small percentage of overall sales because the majority of hospitals and clinics do not maintain these in-house capabilities.

In Puerto Rico, we own and operate one of the two radiopharmacies on the island, where we sell our own products as well as products of third parties to end-users.

In Canada, we operate some direct distribution activities.

In Europe, Canada, Australia, Asia-Pacific and Latin America, we utilize third party distributor relationships to market, sell and distribute our products, either on a country-by-country basis or on a multi-country regional basis.

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

With Double-Crane’s support, we are currently pursuing the Chinese regulatory approval required to commercialize DEFINITY.

In July 2013, we submitted a clinical trial application to the Chinese Food and Drug Administration (“CFDA”) seeking an Import Drug License.

After a very extensive waiting period caused by a large number of drugs seeking CFDA regulatory approval, in February 2016, the CFDA approved our clinical trial application.

In Canada, we operate some direct distribution activities and also rely on third party distributors.

In Europe, Australia, Asia-Pacific and Latin America, we utilize third party distributor relationships to market, sell and distribute our products, either on a country-by-country basis or on a multi-country regional basis.

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

With Double-Crane’s support, we are currently pursuing Chinese regulatory approval required to commercialize DEFINITY.

In July 2013, we submitted a clinical trial application to the NMPA seeking an Import Drug License.

After a very extensive waiting period caused by a large number of drugs seeking NMPA regulatory approval, in February 2016, the NMPA approved our clinical trial application.

Double-Crane has conducted on our behalf three confirmatory clinical trials in pursuit of cardiac, liver and kidney imaging indications, as well as one small pharmacokinetic study.

Double Crane is preparing an application to the CFDA for an Import Drug License for the cardiac indication.

Double Crane is also analyzing the clinical results relating to the liver and kidney indications and will also prepare a CFDA application for those indications.

Our business has modest seasonality as patients may seek to schedule non-urgent diagnostic imaging procedures less frequently during the summer vacation months and over the year-end holidays.

In March 2020, we filed an Import Drug License application with the NMPA for the use of DEFINITY for the echocardiography indication.

We believe this is an important milestone in our efforts to commercialize DEFINITY in China.

For the diagnostic portion of our business, we have some modest seasonality as patients may seek to schedule diagnostic imaging 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, 2020.

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We believe that our key product characteristics, such as proven efficacy, reliability and safety, coupled with our core competencies, such as our efficient manufacturing processes, our established distribution network, our experienced field sales organization and our customer service focus, are important factors that distinguish us from our competitors.

The market for diagnostic medical imaging agents is highly competitive and continually evolving.

Our principal competitors in existing diagnostic modalities include large, global companies that are more diversified than we are and that have substantial financial, manufacturing, sales and marketing, distribution and other resources.

These 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 Medical Radioisotopes.

We cannot anticipate their competitive actions in the same or competing diagnostic modalities, such as significant price reductions on products that are comparable to our own, development of new products 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 current 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.

The markets for our products are highly competitive and continually evolving.

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 DEFINITY, our competitors currently include GE Healthcare and Bracco.

• For a number of our 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 Medical Radioisotopes.

• For PyL, if and when it is approved by the FDA, it will compete with Bracco’s Axumin (fluciclovine F 18).

We also may face competition from Telix Pharmaceuticals Limited, which also has a PSMA-targeted prostate cancer PET diagnostic imaging agent currently under review with the FDA.

• For RELISTOR, our principal competitors include Nektar Therapeutics, 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, there are currently no other FDA approved anticancer treatments in the U.S.

for malignant, recurrent, and/or unresectable pheochromocytoma and paraganglioma.

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

Point Biopharma;

Telix Pharmaceuticals Limited;

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

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 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.

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

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

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.

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

ANSTO’s new Mo-99 processing facility, could eventually increase ANSTO’s production capacity from approximately 2,000 curies per week to 3,500 curies per week with additional committed financial and operational resources.

At full ramp-up capacity, ANSTO’s new facility could provide incremental supply to our globally diversified Mo-99 supply chain and therefore mitigate some risk among our Mo-99 suppliers, although we can give no assurances to that effect and 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.

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.

The NTP Agreement expires on December 31, 2021.

Despite our globally diverse Mo-99 suppliers, we still face challenges in our Mo-99 supply chain.

The NTP processing facility had periodic outages in 2017, 2018 and 2019.

When NTP was not producing, we relied on Mo-99 supply from both IRE and ANSTO

to limit the impact of the NTP outages.

In the second quarter of 2019, ANSTO experienced facility issues in its existing Mo-99 processing facility which resulted in a decrease in Mo-99 available to us.

In addition, as ANSTO transitioned from its existing Mo-99 processing facility to its new Mo-99 processing facility in the second quarter of 2019, ANSTO experienced start-up and transition challenges, which also resulted in a decrease in Mo-99 available to us.

Further, starting in late June 2019 and through the date of this filing, ANSTO’s new Mo-99 processing facility has experienced unscheduled production outages, and we are now relying on IRE and NTP to limit the impact of those ANSTO outages.

Because of these various supply chain constraints, depending on reactor and processor schedules and operations, we have not been able to fill some or all of the demand for our TechneLite generators on certain manufacturing days.

We are also pursuing additional sources of Mo-99 from potential new producers around the world to further augment our current supply.

When NTP was not producing, we relied on Mo-99 supply from both IRE and ANSTO to limit the impact of the NTP outages.

In 2019 and 2020, ANSTO experienced multiple facility issues that resulted in ANSTO outages and volume limitations, during which time we relied on IRE and NTP to limit the impact of those outages and limitations.

Because of the COVID-19 pandemic, we experienced challenges receiving regularly scheduled orders of Mo-99 from our global suppliers, particularly in the second quarter of 2020.

We continue to manage these various supply chain challenges, but depending on reactor and processor schedules and operations, at times we have not been able to fill some or all of the demand for our TechneLite generators on certain manufacturing days.

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.

We are also pursuing additional sources of Mo-99 from potential new producers to further augment our current supply.

In November 2014, we entered into a strategic arrangement with SHINE for the future supply of Mo-99.

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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 IsoSolutions Marketing & Management Inc., which sources the isotope from IRE in Belgium.

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

We also rely on Center for Probe Development and Commercialization (CPDC) 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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We manufacture TechneLite on a highly automated production line, Thallium and Gallium and certain radiochemicals using our cyclotron technology, and we process and finish Xenon and QUADRAMET using our hot cell infrastructure.

We also maintain manufacturing operations at our San Juan, Puerto Rico radiopharmacy and PET manufacturing facility where we manufacture FDG using cyclotron technology.

We also operate a manufacturing facility at Somerset, NJ for AZEDRA that may also provide manufacturing support for 1095 in the future.

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, our cyclotrons 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 highly automated generator production line, our cyclotrons and our other manufacturing assets, 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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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 North Billerica, Massachusetts facility.

PyL and flurpiridaz F 18 will require the creation of a field-based network of specialized PMFs with radioisotope-producing cyclotrons.

The radioisotope used in both PyL and flurpiridaz F 18 is fluorine-18, or F 18, which has a 110 minute half-life, requiring that these products be manufactured and distributed rapidly to end-users.

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 either PyL or flurpiridaz F 18.

PyL or flurpiridaz F 18 is next transferred to a radiopharmacist who prepares and dispenses patient-specific doses from the final product.

Because each of the PMFs manufacturing these products will be deemed by the FDA to be a separate manufacturing site, each will have to be approved by the FDA, and we can give no assurance that the FDA will do this in accordance with the planned roll-out schedule for the products.

In our PyL NDA, we included a limited number of PMFs for approval, and we intend to add in a sequenced manner, using FDA site approval processes, additional PMFs to our manufacturing network in the months following FDA product approval with the goal of having broad availability for the U.S.

population within six months of product approval.

We are also in the final stages of an extensive, multi-year effort to add specialized manufacturing capabilities at our North Billerica, Massachusetts facility.

This project is part of a larger corporate growth strategy to create a competitive advantage in specialized manufacturing.

This project should not only deliver efficiencies and supply chain redundancy for our current portfolio but should also afford us increased flexibility as we consider external opportunities.

We currently expect to be in a position to use this in-house manufacturing capability by early 2021.

This project should not only deliver efficiencies and supply chain redundancy for our current portfolio but should also afford us increased flexibility as we consider additional external opportunities.

We currently expect to make use of this in-house manufacturing capability in late 2021.

However, we can give no assurance that we will be successful in these efforts or that we will be able to successfully manufacture any additional commercial products at our North Billerica, Massachusetts facility.

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Based on our current projections, we believe that we will have sufficient supply of DEFINITY from JHS to meet expected demand.

On May 3, 2016, we entered into a Manufacturing and Supply Agreement with SBL to perform technology transfer and process development services to manufacture and supply a modified formulation of DEFINITY.

On May 3, 2016, we entered into a Manufacturing and Supply Agreement with SBL to perform technology transfer and process development services to manufacture and supply DEFINITY RT.

There are no minimum purchase requirements under this agreement, which has an initial term of five years from the date of first commercial sale and is renewable at our option for an additional five years.

This agreement allows for termination upon the occurrence of certain events, including material breach or bankruptcy of either party.

We cannot give any assurances as to when those technology transfer activities will be completed and when we will begin to receive supply of a modified formulation of DEFINITY from SBL.

We believe DEFINITY RT will become commercially available later in 2021, although that timing cannot be assured.

• Cardiolite —In May 2012, we entered into a Manufacturing and Supply Agreement with JHS for the manufacture of Cardiolite products.

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Under the agreement, JHS has agreed to manufacture products for an initial term of five years from the effective date.

On November 9, 2017, we extended the term until December 31, 2020, and the agreement can be further extended for three additional one-year periods thereafter so long as the parties, using good faith, reasonable efforts, agree to new pricing for the upcoming additional term.

That agreement has now been extended until December 31, 2021, and can be further extended for two additional one-year periods thereafter so long as the parties, using good faith, reasonable efforts, agree to new pricing for the upcoming additional term.

The agreement allows for termination upon the occurrence of specified events, including material breach or bankruptcy by either party.

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Under the agreement, JHS agreed to manufacture NEUROLITE for an initial term of five years from the effective date.

On November 9, 2017, we extended the term of the agreement until December 31, 2020, and the agreement can be further extended for three additional one-year periods thereafter so long as the parties, using good faith, reasonable efforts, agree to new pricing for the upcoming additional term.

The agreement allows for termination upon the occurrence of specified events, including material breach or bankruptcy by either party.

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Based on our current projections, we believe that we will have sufficient supply of NEUROLITE from JHS to meet expected demand.

Although we are pursuing additional third party manufacturing relationships to establish and secure additional long-term or alternative suppliers as described above, we are uncertain of the timing as to when these arrangements could provide meaningful quantities of our products.

See Part I, Item 1A.

“Risk Factors” for information regarding certain risks associated with our manufacturing relationships.

Clinical Development

For the years ended December 31, 2019, 2018 and 2017, we invested $20.0 million , $17.1 million and $18.1 million in research and development (“R&D”), respectively.

Our R&D team includes our Medical Affairs and Medical Information functions, which educate physicians on the scientific aspects of our commercial products and the approved indications.

In addition to the DEFINITY clinical trials in China described above, we currently have three active clinical development programs.

Flurpiridaz F 18—PET Myocardial Perfusion

We have developed flurpiridaz F 18, an internally discovered small molecule radiolabeled with fluorine-18, as an imaging agent used in PET MPI to assess blood flow to the heart.

Today, most MPI procedures use SPECT technology.

Although SPECT imaging used in conjunction with a radiopharmaceutical imaging agent, such as Cardiolite, is most commonly used for MPI studies, PET imaging has gained considerable support in the field of cardiovascular imaging as it offers many advantages to SPECT imaging, including:

higher image quality, increased diagnostic certainty, more accurate risk stratification and reduced patient radiation exposure .

PET imaging has demonstrated broad utility for diagnosis, prognosis, disease staging and therapeutic response.

When used in combination with an appropriate radiopharmaceutical imaging agent, PET imaging can provide important insights into physiologic and metabolic processes in the body and be useful in evaluating a variety of conditions including heart disease, neurological disease and cancer.

In addition, PET MPI imaging could be particularly useful in difficult-to-image patients, including women and obese patients.

The use of PET technology in MPI tests represents a broad emerging application for a technology more commonly associated with oncology and neurology.

We anticipate that the adoption of PET technology in MPI tests will increase significantly in the future.

Flurpiridaz F 18 Clinical Overview and Phase 3 Program

We submitted an Investigational New Drug Application (“IND”) for flurpiridaz F 18 to the FDA in August 2006.

Our clinical program to date has consisted of three Phase 1 studies, a Phase 2 clinical trial, conducted from 2007 to 2010, involving 176 subjects who received PET MPI performed with flurpiridaz F 18 and completed the trial, and a Phase 3 clinical trial (“301 Trial”) conducted from 2011 to 2013.

The 301 Trial was an open-label, multicenter, international study with 755 subjects with known or suspected coronary artery disease (“CAD”) and scheduled for coronary angiography and SPECT imaging who completed the trial and were included in the efficacy analysis.

Subjects underwent flurpiridaz F 18 PET MPI and SPECT MPI studies with coronary angiography used as the truth standard for each.

The study then compared MPI imaging using flurpiridaz F 18 versus SPECT imaging with primary endpoints of superiority for sensitivity (identifying disease) and non-inferiority for specificity (ruling out disease).

In the fourth quarter of 2013, we announced preliminary results from the 301 Trial, and in May 2015, after a re-read of the 301 Trial results, we announced the complete results from the 301 Trial.

Flurpiridaz F 18 appeared to be well-tolerated from a safety perspective, and PET MPI with flurpiridaz F 18 consistently showed a balanced performance in sensitivity and specificity, when compared to coronary angiography, while SPECT imaging results were skewed with low sensitivity and high specificity when compared to coronary angiography.

When results were compared to one another, flurpiridaz F 18 imaging substantially outperformed SPECT imaging in sensitivity but did not meet the non-inferiority endpoint in specificity, implying a substantial and unexpected under-diagnosis of CAD with SPECT imaging in the trial.

In subgroup analyses, the risk-benefit profile of flurpiridaz F 18 appeared to be favorable in women, obese patients, patients with multi-vessel disease and diabetics.

A significantly higher percentage of images were rated as either excellent or good with flurpiridaz F 18 imaging as compared to SPECT imaging, leading to a greater diagnostic certainty of interpretation.

Importantly, radiation exposure associated with flurpiridaz F 18 imaging was reduced to approximately 50% of SPECT imaging.

In addition, no drug-related serious adverse events were observed.

GE Healthcare Collaboration

In April 2017, we announced that we entered into a definitive, exclusive Collaboration and License Agreement (the “License Agreement”) with GE Healthcare for the continued Phase 3 development and worldwide commercialization of flurpiridaz F 18.

Under the License Agreement, GE Healthcare will complete the worldwide development of flurpiridaz F 18, 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.

The second Phase 3 clinical trial is underway, as a prospective, open-label, international, multi-center trial of flurpiridaz F 18 for PET MPI in patients referred for invasive coronary angiography because of suspected CAD.

The trial will enroll up to 650 participants, with a target completion date in the second half of 2020, although that timing cannot be assured.

The primary outcome measure for the trial is the diagnostic efficacy of flurpiridaz F 18 PET MPI in the detection of significant CAD, with secondary outcome measures of diagnostic efficacy of flurpiridaz F 18 PET MPI compared with SPECT MPI in the detection of CAD in all patients.

Secondary analysis will be performed in patients of special clinical interest, such as female, obese and diabetic patients, where current SPECT MPI technologies have shown certain limitations in the diagnostic performance.

LMI 1195 (flubrobenguan F18)

We have developed LMI 1195, an internally discovered small molecule imaging agent for the norepinephrine pathway.

We originally pursued developing LMI 1195 for the diagnostic assessment of ischemic heart failure patients at risk of sudden cardiac death who may benefit from an implantable cardioverter defibrillator (ICD).

However, after multiple interactions with the FDA, we have concluded that the cardiac clinical development program for this indication would be longer and more expensive than we had

initially envisioned.

As a result, we have paused in pursuing this particular indication but may consider other possible cardiac indications in the future.

We are now designing two Phase 3 clinical trials for the use of LMI 1195 for the diagnosis and management of neuroendocrine tumors in pediatric and adult populations, respectively.

The FDA has granted an Orphan Drug designation for the use of LMI 1195 in the management indication.

DEFINITY - LVEF

As part of our microbubble franchise strategy, we conducted two Phase 3, open-label, multicenter studies to evaluate LVEF measurement accuracy and reproducibility of DEFINITY contrast-enhanced and unenhanced echocardiography as compared to non-contrast CMRI used as the truth standard.

The first of the two trials, BENEFIT 1, enrolled 145 subjects.

In addition, analyses of the secondary endpoints revealed no improvement in inter-reader variability between the contrast-enhanced and unenhanced echocardiograms for LVEF assessments.

We will continue to analyze the BENEFIT 1 data, and when the data from BENEFIT 2 are available, we will compile the data sets to analyze the full results of the trials.

See Part I, Item 1A.

“Risk Factors” for information regarding certain risks associated with our clinical development programs.

Strategic Activities

We continue to evaluate a number of different opportunities to acquire or in-license additional products, businesses and technologies to drive our future growth.

We are particularly interested in expanding our presence in oncology, in radiotherapeutics as well as diagnostics.

In addition to the Progenics Transaction described above, we recently entered into a strategic collaboration and license agreement with NanoMab Technology Limited, a privately-held biopharmaceutical company focusing on the development of next generation radiopharmaceuticals for cancer precision medicine.

We believe this collaboration will provide the first broadly-available imaging biomarker research tool to pharmaceutical companies and academic centers conducting research and development on PD-L1 immuno-oncology treatments, including combination therapies.

We can give no assurance as to when or if this collaboration will be successful or accretive to earnings.

In addition to integrating the new assets and programs resulting from the Progenics Acquisition, we continue to seek ways to further expand our portfolio of products and product candidates and how best to optimize the value of our current assets, evaluating a number of different opportunities to collaborate with others or to acquire or in-license additional products, product candidates, businesses and technologies to drive our future growth.

As the Progenics Acquisition indicates, we are particularly interested in expanding our presence in oncology, in both radiotherapeutics and diagnostics.

In May 2019, we commenced an initiative to build out our Pharma Services capabilities by entering into a strategic collaboration and license agreement with NanoMab Technology Limited (“NanoMab”), a privately-held biopharmaceutical company focusing on the development of next generation radiopharmaceuticals for cancer precision medicine.

We believe this collaboration will provide the first broadly-available PD-L1 imaging biomarker research tool to pharmaceutical companies and academic centers conducting clinical trials on immuno-oncology treatments, including combination therapies.

We have also expanded our Pharma Services offering to include PyL for pharmaceutical companies developing PSMA-targeted therapies and have entered into PyL clinical supply agreements with each of Regeneron, Bayer and POINT BioPharma for use of PyL in drug development programs.

We can give no assurance as to when or if any of these Pharma Services collaborations will be successful or accretive to earnings.

In addition, as described above, we continue to expand our microbubble franchise.

We recently announced a strategic development and commercial collaboration with Cerevast in which our microbubble will be used in connection with Cerevast’s ocular ultrasound device to target improving blood flow in occluded retinal veins in the eye.

In October 2020, we announced a strategic collaboration with Insightec which will use our microbubbles in connection with Insightec’s transcranial guided focused ultrasound device for the treatment of glioblastoma as well as other neurodegenerative conditions.

Glioblastoma is a lethal and devastating form of brain cancer with median survival of 15 months after diagnosis.

Previously, we announced a strategic commercial supply agreement with CarThera for the use of our microbubbles in combination with SonoCloud, a proprietary implantable device in development for the treatment of recurrent glioblastoma.

We also previously announced a strategic development and commercial collaboration with Cerevast in which our microbubbles will be used in connection with Cerevast’s ocular ultrasound device to improve blood flow in occluded retinal veins in the eye.

Retinal vein occlusion is one of the most common causes of vision loss worldwide.

We also recently announced a strategic commercial supply agreement with CarThera for the use of our microbubbles in combination with SonoCloud, a proprietary implantable device in development for the treatment of recurrent glioblastoma, Glioblastoma is a lethal and devasting from of brain cancer with median survival of 15 months after diagnosis.

See Part I, Item 1A.

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Trademarks, Service Marks and Trade Names

We own various trademarks, service marks and trade names, including, among others, DEFINITY, TechneLite, Cardiolite, Neurolite, Vialmix, Quadramet, Luminity and Lantheus Medical Imaging.

We own various trademarks, service marks and trade names, including, among others, DEFINITY, DEFINITY RT, TechneLite, Cardiolite, NEUROLITE, VIALMIX, VIALMIX RFID, QUADRAMET, Luminity, PyL, AZEDRA, AZEDRA Service Connection, RELISTOR, Lantheus, Lantheus Medical Imaging, Progenics, Progenics Pharmaceuticals, Molecular Insight, EXINI, PyL Research Access Program and Find, Fight and Follow.

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

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patents, 804 issued foreign patents, 49 pending U.S.

patent applications and 160 pending foreign applications.

These patents and patent applications include claims covering the composition of matter and methods of use for all of our preclinical and clinical stage agents.

patent applications and 239 pending foreign applications, owned or exclusively licensed.

We have patent protection on certain of our commercial products and on all of our clinical development candidates.

We typically seek patent protection in major markets around the world, including, among others, the U.S., Canada, Western Europe, Asia, and Latin America.

DEFINITY - We continue to actively pursue additional patents in connection with DEFINITY, both in the U.S.

All patent terms described below are presented without giving effect to any applicable patent term adjustments or regulatory extensions.

DEFINITY - We continue to actively pursue additional patents in connection with DEFINITY and DEFINITY RT, both in the U.S.

and internationally.

In the U.S., we have an Orange Book-listed method of use patent expiring in March 2037 and additional manufacturing patents that are not Orange Book-listed expiring in 2021, 2023 and 2037.

Outside of the U.S., while our DEFINITY patent protection and regulatory exclusivity have generally expired, we are currently prosecuting additional patents to try to obtain similar method of use patent protection as granted in the U.S.

for DEFINITY we own a total of four Orange Book-listed method of use patents, one of which expires in 2035 and three of which expire in 2037, as well as additional manufacturing patents that are not Orange Book-listed expiring in 2021, 2023 and 2037.

for DEFINITY RT, we own a total of five Orange Book-listed patents, including a composition of matter patent which expires in 2035.

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

additional VIALMIX RFID patent applications have been submitted in major markets throughout the world.

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.

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

If we were to (i) receive any such Notice in the future, (ii) bring a patent infringement suit against the ANDA applicant within 45 days of receiving such Notice, and (iii) successfully obtain the full 30 month stay, then the ANDA applicant would be precluded from commercializing a generic candidate prior to the expiration of such 30 month stay period and potentially thereafter depending on how a patent dispute is resolved.

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

TechneLite - We currently have patent protection in the U.S.

and various foreign countries on certain component technology expiring in 2029.

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

and various foreign countries on certain component technology expiring in 2029, and we are pursuing additional patent protection in the U.S.

and world-wide on other component technology that, if granted, would expire in 2040.

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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.

Clinical Development Candidates - We have patents and patent applications in numerous jurisdictions covering composition, use, formulation and manufacturing of flurpiridaz F 18, including in the U.S.

a composition patent expiring in 2026, a method of use patent expiring in 2028 and a method of manufacturing patent expiring in 2031, in the absence of any regulatory extension, and various patent applications, one of which, if granted, will expire in 2033 in the absence of any patent term adjustment or regulatory extensions.

We also have patents and patent applications in numerous jurisdictions covering composition, use, and manufacture of LMI 1195, including in the U.S.

a composition patent expiring in 2030, a method of use patent expiring in 2027, and manufacturing-related patents expiring in 2031 and 2032, in the absence of any regulatory extension, and patent applications which, if granted, will expire in 2027 and in 2031 in the absence of any patent term adjustment or regulatory extensions.

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 three separate settlement agreements that have granted non-exclusive limited licenses with respect to certain RELISTOR subcutaneous injection applications.

The non-exclusive limited licenses with two parties are currently effective on January 1, 2028 and the third 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 2022 and 2024.

In addition, we own pending applications worldwide for manufacturing improvements, and the resulting compositions which, if issued, would expire in 2035.

PyL - The PyL patent family was licensed from the Johns Hopkins University (“JHU”).

Patent protection for composition of matter patents, radiolabeled forms of the compound, and methods of use in the U.S.

expire in 2029 and 2030.

Corresponding patents issued or pending worldwide, all expire in 2029.

Process improvement patent applications are pending worldwide and, if issued, would expire in 2037.

flurpiridaz F 18 - We own patents and patent applications in numerous jurisdictions covering composition, use, formulation and manufacturing, including in the U.S.

a composition of matter patent expiring in 2026, a formulation patent expiring in 2032, a method of use patent expiring in 2028, and manufacturing-related patents expiring in 2031 and 2033, and various patent applications, some of which, if granted, will expire in 2033.

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.

and Europe expiring in 2027.

Additional U.S.

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

LMI 1195 - We own patents and patent applications in numerous jurisdictions covering composition, use, and manufacturing, including in the U.S.

a composition of matter patent expiring in 2030, a method of use patent expiring in 2027, and manufacturing-related patents expiring in 2031 and 2032, and patent applications which, if granted, will expire in 2027 and in 2031.

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

from 2029 to 2030, and expiring worldwide in 2029.

In-licensed patents relating to reagents for radiolabeling expire in the U.S.

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

The patents on this technology expire in the U.S.

in 2032 and outside of the U.S.

Patent applications are pending in the U.S.

and worldwide relating to aBSI improvements which, if issued will expire in 2040.

PSMA-AI – U.S.

Patents and pending patent applications worldwide relating to automated medical image analysis, have expiration ranges from 2037 to 2040.

PSMA Antibody TTC – We own and in-license composition of matter patents on PSMA antibodies expiring in the U.S.

in 2022 and 2023 and outside of the U.S.

In addition to patents, we rely, where necessary, upon unpatented trade secrets and know-how, proprietary information and continuing technological innovation to develop and maintain our competitive position.

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To the extent that our collaborators, employees and consultants use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.

In addition, we license a limited number of third party technologies and other intellectual property rights that are incorporated into some elements of our drug discovery and development efforts.

These licenses are not material to our business, and the technologies can be obtained from multiple sources.

We are currently party to separate royalty-free, non-exclusive, cross-licenses with each of Bracco, GE Healthcare and Imcor Pharmaceutical Company.

These cross-licenses give us freedom to operate in connection with contrast enhanced ultrasound imaging technology.

In addition, we license third party technologies and other intellectual property rights that are incorporated into some elements of our drug discovery and development efforts.

Some of these licenses are material to our business – for example, the licenses of the patent rights on RELISTOR from Wyeth LLC and on the PyL patent family from JHU.

See Part I, Item 1A.

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Department of Health and Human Services (“HHS”), Health Canada, the European Medicines Agency (“EMA”), the U.K.

Medicines and Healthcare Products Regulatory Agency (“MHRA”), the CFDA and various state and provincial boards of pharmacy, state and provincial controlled substance agencies, state and provincial health departments and/or comparable state and provincial agencies, as well as foreign agencies, and certain accrediting bodies depending upon the type of operations and location of product distribution, manufacturing and sale.

Medicines and Healthcare Products Regulatory Agency (“MHRA”), the NMPA and various state and provincial boards of pharmacy, state and provincial controlled substance agencies, state and provincial health departments and/or comparable state and provincial agencies, as well as foreign agencies, and certain accrediting bodies depending upon the type of operations and location of product distribution, manufacturing and sale.

The FDA and various state regulatory authorities regulate the research, testing, manufacture, safety, labeling, storage, recordkeeping, premarket approval, marketing, advertising and promotion, import and export, and sales and distribution of pharmaceutical products in the U.S.

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generally involves the following:

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

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

Performance of adequate and well-controlled human clinical studies according to 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, or NDA, for a new drug;

• 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;

• 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;

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

Clinical trial sponsors may request a Special Protocol Assessment (“SPA”) from the FDA.

The FDA’s SPA process creates a written agreement between the sponsoring company and the FDA regarding the clinical trial design and other clinical trial issues that can be used to support approval of an agent.

The SPA is intended to provide assurance that, if the agreed-upon clinical trial protocols are followed and the trial endpoints are achieved, then the data may serve as the primary basis for an efficacy claim in support of an NDA.

However, the SPA agreement is not a guarantee of an approval of an agent or any permissible claims about the agent.

In particular, the SPA is not binding on the FDA if public health concerns become evident that are unrecognized at the time that the SPA agreement is entered into, other new scientific concerns regarding product safety or efficacy arise, or if the clinical trial sponsor fails to comply with the agreed upon clinical trial protocols.

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.

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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.

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

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.

A REMS could add training requirements for healthcare professionals, safety communications efforts and limits on channels of distribution, among other things.

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Whether a REMS would be imposed on any of our products and any resulting financial impact is uncertain at this time.

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.

In addition, if a product that has Orphan Drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to Orphan Drug exclusivity, which means the FDA may not approve any other application to market the same drug for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where the manufacturer is unable to assure sufficient product quantity.

Any drug products for which we receive FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements, and complying with FDA promotion and advertising requirements.

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The Hatch-Waxman Act also provides for a period of statutory protection for new drugs that receive NDA approval from the FDA.

If the FDA approves a Section 505(b) (1) NDA for a new drug that is a new chemical entity, meaning that the FDA has not previously approved any other new drug containing the same active moiety, then the Hatch-Waxman Act prohibits the submission or approval of an ANDA or a Section 505(b) (2) NDA for a period of five years from the date of approval of the NDA, except that the FDA may accept an application for review after four years under certain circumstances, specifically a patent challenge for one or more patents listed by the NDA holder in FDA’s publication, Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”), submitted in a “Paragraph IV” Certification.

The Hatch-Waxman Act will not prevent the filing or approval of a full NDA, as opposed to an ANDA or Section 505(b) (2) NDA, for any drug, but the competitor would be required to conduct its own clinical trials, and any use of the drug for which marketing approval is sought could not violate another NDA holder’s patent claims.

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• imposing a non-deductible annual fee on pharmaceutical manufacturers or importers who sell brand name prescription drugs to specified federal government programs.

amending the federal self-referral laws to require referring physicians ordering certain diagnostic imaging services to inform patients under certain circumstances that the patients may obtain the services from other local and unaffiliated suppliers (which may affect the setting in which a patient obtains services).

The Healthcare Reform Act also amended the federal self-referral laws, requiring referring physicians to inform patients under certain circumstances that the patients may obtain services, including MRI, computed tomography (“CT”), PET and certain other diagnostic imaging services, from a provider other than that physician, another physician in his or her group practice, or another individual under direct supervision of the physician or another physician in the group practice.

The referring physician must provide each patient with a written list of other suppliers who furnish those services in the area in which the patient resides.

These new requirements could have the effect of shifting where certain diagnostic medical imaging procedures are performed.

These requirements could have the effect of shifting where certain diagnostic medical imaging procedures are performed.

The Healthcare Reform Act has been subject to political and judicial challenges.

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In December 2019, a federal appeals court agreed that the individual mandate provision was unconstitutional, but remanded the case back to the district court to assess more carefully whether any provisions of the Healthcare Reform Act were severable and could survive.

Pending action by the district court and resolution of any appeals, which could take some time, the Healthcare Reform Act is still operational in all respects.

In November 2020, the U.S.

Supreme Court heard an appeal of the federal appeals court decision, but has not opined on the constitutionality of the individual mandate or the severability of the remaining aspects of the Healthcare Reform Act.

Pending resolution of this case, the Healthcare Reform Act is still operational.

Recently, there has been considerable public and government scrutiny of pharmaceutical pricing and proposals to address the perceived high cost of pharmaceuticals.

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Certain proposals in the blueprint, and related drug pricing measures proposed since the blueprint, could cause significant operational and reimbursement changes for the pharmaceutical industry.

As another example, in October 2018, CMS solicited public comments on potential changes to payment for certain Medicare Part B drugs, including reducing the Medicare payment amount for selected Medicare Part B drugs to more closely align with international drug prices.

As another example, legislation passed in 2019 revised how certain prices reported by manufacturers under the Medicaid Drug Rebate Program are calculated, a revision that the Congressional Budget Office has estimated will save the federal government approximately $3 billion in the next ten years.

As an example, legislation passed in 2019 revised how certain prices reported by manufacturers under the Medicaid Drug Rebate Program are calculated, a revision that the Congressional Budget Office has estimated will save the federal government approximately $3.0 billion in the next ten years.

As another example, in November 2020, CMS issued an interim final rule that announced a new “most favored nation” payment model for certain Medicare Part B drugs, which would reduce the Medicare payment amount for such drugs to the lowest price that drug manufacturers receive in other similar countries.

(Multiple federal courts have issued temporary injunctions blocking implementation of this final rule).

Efforts by government officials or legislators to implement measures to regulate prices or payment for pharmaceutical products could limit our flexibility in establishing prices for our products or otherwise adversely affect our business if implemented.

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General legislative cost control measures may also affect reimbursement for our products or services provided with our products.

The Budget Control Act, as amended by the Bipartisan Budget Act of 2019, resulted in the imposition of 2% reductions in Medicare (but not Medicaid) payments to providers beginning in 2013 and will remain in effect through 2029 unless additional Congressional action is taken.

The Budget Control Act, as amended by the Bipartisan Budget Act of 2019, resulted in the imposition of 2% reductions in Medicare (but not Medicaid) payments to providers beginning in 2013 and will remain in effect through fiscal year 2030 unless additional Congressional action is taken.

The Coronavirus Aid, Relief, and Economic Security (CARES) Act suspended the 2% payment adjustment for dates of service from May 1 through December 31, 2020, and the Consolidated Appropriations Act 2021 subsequently extended this suspension until March 31, 2021.

Any significant spending reductions affecting Medicare, Medicaid or other publicly funded or subsidized health programs that may be implemented and/or any significant taxes or fees that may be imposed on us could have an adverse impact on our business results of operations, financial condition and cash flows.

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Our activities relating to the sale and marketing of our products may be subject to scrutiny under these laws.

Laws and regulations have also been enacted by the federal government and various states to regulate the sales and marketing practices of pharmaceutical manufacturers.

Laws and regulations have also been enacted by the U.S.

federal government and various states, as well as by countries outside of the U.S., to regulate the sales and marketing practices of certain entities including pharmaceutical and device manufacturers.

The laws and regulations generally limit financial interactions between manufacturers and health care providers;

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federal government;

and/or require disclosure to the government and/or public of financial interactions (so-called “sunshine laws”).

and/or require disclosure by pharmaceutical and device manufacturers to the government and/or public of financial interactions or other financial relationships with health care providers and other entities such as teaching hospitals (so-called “sunshine laws”).

The Healthcare Reform Act requires manufacturers to submit information to the FDA on the identity and quantity of drug samples requested and distributed by a manufacturer during each year.

Many of these laws and regulations contain ambiguous requirements or require administrative guidance for implementation.

Given the lack of clarity in laws and their implementation, our activities could be subject to the penalty provisions of the pertinent federal and state laws and regulations.

Data Privacy and Security

We are subject to data protection laws and regulations that address privacy and data security.

The legislative and regulatory landscape for data protection continues to evolve, and in recent years there has been an increasing focus on privacy and data security issues.

The laws and regulations include requirements that can be unclear in their scope, nature, and required implementation by regulated entities.

If we fail to comply with such laws and regulations, we could be subject to penalties and administrative actions under such laws and regulations.

Data Privacy, Security and Breach Notification

We are subject to data protection laws and regulations that set forth data privacy, security, and breach notification requirements.

The legislative and regulatory landscape for data protection continues to evolve, and in recent years there has been an increasing focus on data protection and other data privacy and security issues.

In the United States, numerous federal and state laws and regulations, including state data breach notification laws, state health information privacy laws and federal and state consumer protection laws govern the collection, use, disclosure and protection of health-related and other personal information.

Failure to comply with data protection laws and regulations could result in government enforcement actions, which could include civil or criminal penalties, private litigation and/or adverse publicity and could negatively affect our operating results and business.

In addition, we may obtain health information from third parties (e.g., healthcare providers who prescribe our products) that are subject to privacy and security 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”).

While we believe that we are neither a “covered entity” nor “business associate” subject directly to regulation under HIPAA, HIPAA’s criminal provisions can apply to entities other than “covered entities” or “business associates” in certain

circumstances.

In addition to establishing restrictions on how personal information may be collected, used, and disclosed, these laws and regulations provide various rights to data subjects with respect to their personal information and establish requirements for how personal information must be secured.

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.

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”).

Accordingly, we could be subject to criminal penalties if we knowingly obtain or disclose individually identifiable health information from a HIPAA-covered entity in a manner that is not authorized or permitted.

The collection and use of personal health data in the European Union is governed by the provisions of the General Data Protection Regulation, or GDPR, which came into effect in May 2018.

This regulation imposes several requirements relating to the consent of the individuals to whom the personal data relates, the information provided to the individuals, notification of data processing obligations to the competent national data protection authorities and the security and confidentiality of the personal data.

In addition, a growing number of jurisdictions outside of the United States have enacted robust data protection laws.

Certain of these laws have extraterritorial application.

For example, the processing of personal data in the European Union is governed by the provisions of the General Data Protection Regulation, or GDPR, which came into effect on May 25, 2018.

The GDPR applies to an entity established in the EU and extraterritorially to an entity outside of the EU that offers goods or services to, or monitors the behavior of, individuals located in the EU.

Certain “special categories” of personal data, including data concerning health, are subject to enhanced protections under the GDPR.

This regulation imposes several requirements on the controllers and processors of personal data, including the obligation to comply with various rights that individuals have with respect to their personal data and restrictions on the processing of personal data, and to provide notice of data processing obligations to the competent national data protection authorities.

The GDPR also imposes strict rules on the transfer of personal data out of the European Union to the United States.

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In the United States, several state legislatures are considering enacting new data privacy legislation.

One example of such legislation that has already been passed is the California Consumer Privacy Act (“CCPA”), which took effect on January 1, 2020 and imposed many requirements on businesses that process the personal information of California residents.

Many of the CCPA’s requirements are similar to those found in the GDPR, including requiring businesses to provide notice to data subjects regarding the information collected about them and how such information is used and shared, and providing data subjects the right to request access to such personal information and, in certain cases, request the erasure of such personal information.

The CCPA also affords California residents the right to opt-out of “sales” of their personal information.

One example of such legislation that has already been passed is the California Consumer Privacy Act (“CCPA”), which took effect on January 1, 2020 and

imposes many requirements on certain for-profit businesses that process the personal information of California residents.

Many of the CCPA’s requirements are similar to those found in the GDPR, including requiring businesses to provide notice to data subjects regarding the information collected about them and how such information is used and shared, and providing data subjects various rights, such as the right to request access to their personal information and, in certain cases, request the erasure of such personal information.

The CCPA also affords California residents the right to opt-out of the “sale” of their personal information.

In addition, the CCPA requires regulated businesses to implement reasonable security procedures and practices to protect personal information.

The CCPA contains significant penalties for companies that violate its requirements.

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.

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.

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 California Attorney General will have authority to begin enforcing the CPRA’s amendments to the CCPA beginning on July 1, 2022.

Antitrust and Competition Laws

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This license requires that we provide financial assurance demonstrating our ability to cover the cost of decommissioning and decontaminating (“D&D”) the Billerica site at the end of its use as a nuclear facility.

In addition, we have a radioactive production facility in San Juan, Puerto Rico, where we must also maintain a number of environmental permits and nuclear licenses.

As of December 31, 2019 , we currently estimate the D&D cost of both sites to be approximately $26.9 million .

In addition, we have a radioactive production facility in Somerset, NJ where we must also maintain a number of environmental permits and nuclear licenses.

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, 2020, we currently estimate the D&D cost of all of our manufacturing sites (including our Puerto Rico radiopharmacy which we sold on January 29, 2021) to be approximately $26.9 million.

As of December 31, 2020 and 2019, we have a liability recorded associated with the fair value of the asset retirement obligations of $14.0 million and $12.9 million, respectively.

We currently provide this financial assurance in the form of surety bonds.

We also actively monitor and seek to reduce our solid waste, energy and water usage, waste water discharge and greenhouse gas emissions.

We generally contract with third parties for the disposal of wastes generated by our operations.

Prior to disposal, we store any low level radioactive waste at our facilities until the materials are below regulatory limits, as allowed by our licenses and permits.

In 2020, we developed a stormwater management operations and maintenance plan to minimize stormwater pollution from high impact activities.

Improvements we made include (i) the regular inspection and cleaning of catch basins and piping to reduce sediment and debris wash out to adjacent wetlands;

(ii) increasing street and parking lot cleaning to reduce pollutant run off;

(iii) updating our snow removal plan at our North Billerica site to reduce the impact to adjacent wetlands;

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 our North Billerica buildings against a yearly baseline, national medians, and other similar buildings.

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

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“Risk Factors” for information regarding certain risks associated with environmental matters.

Human Capital Management

As of December 31, 2020, we had 595 employees, of which 569 were located in the U.S.

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None of our employees are represented by a collective bargaining agreement, and we believe that our relationship with our employees is good.

Diversity, Inclusion, Ethics and Compliance

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

We have a female CEO, 50% of our Vice Presidents and above are women, and approximately 44% 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 candidates in the spirit of diversity and inclusion.

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

Our Code of Conduct and Ethics reflects the Company’s commitment to corporate integrity and the underlying business practices and principles of behavior that support this commitment.

Each year our employees complete mandatory training that includes anti-bribery/anti-corruption rules, insider trading prohibitions, confidentiality obligations, as well as specialized training in healthcare industry marketing practices.

We also have a formal Ethics and Compliance Committee that develops, implements and overseas our ethics and compliance programs.

Compensation and Benefits

We seek to provide pay, benefits, and services that are competitive to market and create incentives to attract and retain employees.

Our compensation package includes market-competitive pay, cash bonuses and restricted stock and other equity grants to certain levels of employees, health care and retirement benefits, paid time off and family leave, among others.

We are focused on pay equity and regularly assess pay among similar roles and responsibilities throughout our organization and in comparison to our peer group.

Communication and Engagement

We believe that our success depends on employees understanding how their work contributes to the Company’s overall strategy.

To this end, we utilize a variety of channels to facilitate open and direct communication, including:

(i) quarterly town hall meetings with our executive team;

(ii) regular ongoing update communications;

(iii) employee engagement surveys;

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

We also established various employee recognition award programs to recognize and reward employees for specific outstanding accomplishments and to foster a positive employee relations climate.

Health, Wellness and Safety

We are committed to the health and safety of our employees, patients and other partners in the healthcare community.

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.

With respect to the COVID-19 pandemic, we operate a “Pandemic Response Team” to implement and oversee appropriate precautions to minimize the spread of COVID-19 in our teams and communities.

We continue to have all non-critical employees and contractors work-remotely and avoid non-essential work-related travel.

Further, we established a “Return to Office” team to develop plans for employees to safely return to all our facilities.

Corporate History

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On June 30, 2015, we completed an initial public offering (“IPO”) of our common stock.

We completed our acquisition of Progenics Pharmaceuticals, Inc.

on June 19, 2020.

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

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Information contained on our website shall not be deemed incorporated into, or to be part of this Annual Report on Form 10-K, and any website references are not intended to be made through active hyperlinks.

Our reports filed with, or furnished to, the SEC are also available on the SEC’s website at www.sec.gov, and for Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q, in an XBRL (Extensible Business Reporting Language) format.

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

Our reports filed with, or furnished to, the SEC are also available on the SEC’s website at www.sec.gov, and for Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q, in an Inline Extensible Business Reporting Language (“iXBRL”) format.

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