What changed in this filing

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Item 1. Business

2023-02-23 compared with 2022-02-24 · 256 added, 316 removed, 590 unchanged (49% of the section changed)

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

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

We classify our products in three categories:

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

Our leading precision diagnostic products assist healthcare professionals (“HCPs”) Find and Follow diseases in non-oncologic conditions.

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

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

Our strategic partnerships focus on facilitating precision medicine through the use of biomarkers, digital solutions and radiotherapeutic platforms, and also includes our license of RELISTOR to Bausch Health Companies, Inc.

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

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

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

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

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

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

We sell our products outside the U.S.

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

Our headquarters are located in North Billerica, MA, with additional offices in Somerset, NJ;

Montreal, Canada and Lund, Sweden.

In the first quarter of 2021, we completed the evaluation of our operating and reporting structure, including the impact on our business of the acquisition of Progenics and the sale of our Puerto Rico subsidiary, which resulted in a change in our operating segments to one reportable business segment.

On May 27, 2021, we announced that the FDA had approved PYLARIFY, an F 18-labeled PET imaging agent targeting prostate-specific membrane antigen (“PSMA”).

PYLARIFY is a product in our radiopharmaceutical oncology product category.

We commercially launched PYLARIFY in the U.S.

in June 2021.

During 2021, we announced that our subsidiary, EXINI, was granted 510(k) clearance by the FDA in the U.S.

and a CE marking in Europe for aPROMISE.

We commercially launched aPROMISE under the name PYLARIFY AI in the U.S.

in November 2021.

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

Exclusive License for PNT2002 & PNT2003

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

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

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

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

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

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

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

Our Portfolio of Commercial Products

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Our commercial products in our Precision Diagnostics category include the following:

• DEFINITY is an injectable microbubble ultrasound enhancing agent with perflutren-containing lipid microspheres that is used in ultrasound exams of the heart, also known as echocardiography exams.

DEFINITY requires refrigerated storage 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.

DEFINITY RT is a modified formulation of DEFINITY that allows both storage and shipment at room temperature and provides clinicians an additional choice for greater utility of this formulation in broader clinical settings.

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

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

One formulation of DEFINITY requires refrigerated storage.

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

The indication for both formulations in the U.S.

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

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

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

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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.

Radiopharmaceutical Oncology

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

• PYLARIFY (also known as piflufolastat F 18, 18F-DCFPyL or PyL) is an F 18-labelled PSMA-targeted PET imaging agent used with PET/computed tomography (“CT”) technology that enables visualization of lymph nodes, bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer.

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

PYLARIFY is indicated in the U.S.

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

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

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

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

• 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.

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

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

aBSI is FDA cleared and CE marked.

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

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

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

(“FUJIFILM”) under the name BONENAVI®.

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

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

Additional Information about our Product Categories

Precision Diagnostics

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.

Continued Growth of DEFINITY

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

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

The term DEFINITY includes its activated and non-activated forms.

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

The term DEFINITY includes its activated and non-activated forms and the two formulations it is commercially available in;

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

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

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

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Based on estimates from third party sources, we believe there were approximately 28 to 34 million echocardiograms performed in the U.S.

in 2020 (the latest time period for which full year data is available and which also included the estimated impacts of COVID-19 on procedure volumes).

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

Assuming that between 20% and 30% of echocardiograms produce suboptimal images, as stated in the clinical literature, we estimate that approximately 6 to 10 million echocardiograms in 2021 produced suboptimal images.

Since its launch in 2001, DEFINITY has been used in imaging procedures in more than 21 million studies throughout the world.

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

segment for ultrasound enhancing agents in echocardiography procedures as of December 2021.

DEFINITY currently competes with Optison, a GE Healthcare product, Lumason, a Bracco Diagnostics Inc.

(“Bracco”) product, 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.

We estimate that, as of December 31, 2022, DEFINITY had over 80% share of the U.S.

segment for ultrasound enhancing agents in echocardiography procedures.

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

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

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

See Part I, Item 1A.

“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.

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

and internationally.

for DEFINITY, we have 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 2023 and 2037.

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

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

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

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

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we have submitted additional VIALMIX RFID patent applications 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) either the marketing of that generic candidate does not infringe the Orange Book-listed patent(s) or the Orange Book-listed patent(s) is invalid.

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

With respect to the Orange Book-listed patent(s) covering an innovator product, the ANDA or Section 505(b)(2) applicant (if relying on studies related to the innovator product) (each, the “Applicant”) must give a notice (a “Notice”) to the innovator of its certification that its generic candidate will not infringe the innovator’s Orange Book-listed patent(s) or that the Orange Book-listed patent(s) is invalid.

The innovator can then file suit against the Applicant within 45 days of receiving the Notice, and FDA approval to commercialize the generic candidate will be stayed (that is, delayed) for up to 30 months (measured from the date on which a Notice is received) while the patent dispute between the innovator and the Applicant is resolved in court.

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

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

If we were to (i) receive any such Notice in the future, (ii) bring a patent infringement suit against the Applicant within 45 days of receiving that Notice, and (iii) successfully obtain the full 30-month stay, then the 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.

Solely by way of example and not based on any knowledge we currently have, if we received a Notice from an Applicant in March 2022 and the full 30-month stay were obtained, then the Applicant would be precluded from commercialization until at least September 2024.

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

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

• DEFINITY RT - DEFINITY RT became commercially available in the fourth quarter of 2021.

A modified formulation of DEFINITY that allows both storage and shipment at room temperature, DEFINITY RT provides clinicians an additional choice and allows for greater utility of this formulation in broader clinical settings.

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 Microbubble Franchise below).

• VIALMIX RFID - VIALMIX RFID, our next-generation activation device designed specifically for both DEFINITY and DEFINITY RT, became commercially available in the fourth quarter of 2021.

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 with the VIALMIX RFID activation device.

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

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

As of February 23, 2022, DEFINITY manufactured at this facility is commercially available.

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

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 challenges in the near to intermediate term.

See “Intellectual Property – Patents” below.

As noted above, DEFINITY is activated through the use of medical devices branded as VIALMIX and VIALMIX RFID.

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.

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

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

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

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

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

See Part I, Item 1A.

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

“Management’s Discussion and Analysis of Financial Condition and Results of Operations - Comparison of the Periods Ended December 31, 2021 and 2020 and Comparison of the Periods Ended December 31, 2020 and 2019 - Revenues” for further information on total revenue contributed by DEFINITY in each of our last three fiscal years.

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

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

TechneLite is a self-contained system or generator of Tc-99m, a radioactive isotope with a six hour half-life, used by radiopharmacies to prepare various nuclear imaging agents.

Tc-99m results from the radioactive decay of Mo-99, itself a radioisotope with a 66-hour half-life produced in nuclear research reactors around the world from enriched uranium.

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

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

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

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

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The sterile saline is pulled through the generator where it attracts Tc-99m resulting from the radioactive decay of Mo-99 within the generator column.

The Tc-99m-containing radioactive saline is then pulled into the vacuum vial and subsequently combined by a radiopharmacist with the applicable imaging agent, and individual patient-specific radiolabeled imaging agent doses are then prepared.

The Tc-99m-containing radioactive saline is then pulled into a vacuum vial and subsequently combined by a radiopharmacist with the applicable imaging agent, which allows the preparation of individual patient-specific radiolabeled imaging agent doses.

When administered, the imaging agent binds to specific tissues or organs for a period of time, enabling the Tc-99m to illuminate the functional health of the imaged tissues or organs in a diagnostic image.

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

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

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

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

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

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

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

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

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

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

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

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

In addition, TechneLite has patent protection in the U.S.

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

and various foreign countries on certain component technology currently until 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.

See Part II, Item 7.

Radiopharmaceutical Oncology

PYLARIFY Approval and Commercial Launch

Continued Growth of PYLARIFY

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

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

Based on estimates from third party sources regarding the incidence of prostate cancer in men in the U.S., we believe the potential market size for PSMA PET imaging agents could be up to 220,000 annual scans, comprised of 90,000 scans for patients with intermediate, unfavorable or high/very high risk of suspected metastases of prostate cancer and 130,000 scans for patients with suspected recurrence of prostate cancer.

Because we are in the process of launching this imaging agent, we can give no assurance as to how clinical practice may evolve or what our ultimate market penetration may be.

The approval of PYLARIFY was based on data from two Company-sponsored pivotal studies (“OSPREY” and “CONDOR”) designed to establish the safety and diagnostic performance of PYLARIFY across the prostate cancer disease continuum.

Results from OSPREY (Cohort A) demonstrated improvement in specificity and positive predictive value of PYLARIFY PET imaging over conventional imaging in men at risk for metastatic prostate cancer prior to initial definitive therapy.

CONDOR studied men with biochemical recurrent prostate cancer.

In patients with biochemical recurrent prostate cancer and non-informative baseline imaging, PYLARIFY demonstrated high correct localization and detection rates, including in patients with early recurrent disease with low but rising PSA blood levels (median PSA 0.8 ng/mL).

Upon commercial launch in June 2021, PYLARIFY was immediately available in select parts of the U.S.

Over the course of the remainder of 2021, PYLARIFY availability expanded into additional regions and is now broadly available nationwide.

We continue to expand our geographic coverage, customer contracting and market access coverage to serve our customers and the U.S.

prostate cancer community.

The commercial launch of PYLARIFY is complex and expensive.

During 2021, we hired additional employees to assist us with the commercialization of PYLARIFY, including in sales, marketing, reimbursement, quality and medical affairs.

To manufacture PYLARIFY, we assembled and are qualifying a nationwide network of PMFs with radioisotope-producing cyclotrons that make F 18, which has a 110-minute half-life, so PYLARIFY is manufactured and distributed rapidly to end-users.

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

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

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

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

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

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

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

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

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

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

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

Although PYLARIFY is now broadly available nationwide and we continue to qualify additional PMFs, we can give no assurance that the FDA will continue to approve PMFs in accordance with our planned roll-out schedule.

If FDA approval of manufacturing sites is delayed or withdrawn, our future business, results of operations, financial condition and cash flows could be adversely affected.

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

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

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

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

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

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

Under this initiative, we would enter into a fee-for-service arrangement under which the academic medical center’s PMF would manufacture and supply batches of PYLARIFY, and its radiopharmacy would prepare patient-ready unit doses, in each case for and on behalf of us.

We would then sell

those unit doses to the academic medical center’s hospitals and clinics, and in some instances, to additional customers in the academic medical center’s geographic area, in each case, under separate purchase agreements.

The academic medical center’s PMF’s ability to manufacture and supply batches of PYLARIFY will be subject to FDA approval, and we can give no assurance that the FDA will approve such PMFs in accordance with our planned roll-out schedule.

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

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

In addition, effective January 1, 2022, CMS granted Transitional Pass-Through Payment Status in the hospital outpatient setting (“TPT Status”) for PYLARIFY, enabling traditional Medicare to provide an incremental payment to our customers for PET/CT scans performed with PYLARIFY in that setting.

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

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

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

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

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

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

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

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

After TPT Status expires, under current Medicare rules, PYLARIFY, similar to other diagnostic radiopharmaceuticals, would not be separately reimbursed in the hospital outpatient setting but rather would be included as part of the facility fee a hospital otherwise receives for a PET/CT imaging procedure, and the facility fee does not always cover the cost of a drug used in the procedure.

We can give no assurance that any CMS reimbursement in the hospital outpatient setting that follows the expiration of TPT Status will be adequate to cover the cost of PYLARIFY used in a PET/CT imaging procedure.

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

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

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

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

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

and internationally.

for PYLARIFY, we have four Orange Book-listed patents, including composition of matter patents, which expire in 2030 and 2037.

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

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

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

See Part I, Item 1A.

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

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

Strategic Partnerships and Other Revenue

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 acquire or in-license additional products, product candidates, businesses and technologies to drive our future growth.

To the extent a strategic partnership relates to an approved product or potential new indication of an approved product, we report our revenue generated by that strategic partnership under the applicable product category.

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

We continue to seek ways to further increase the overall value of our portfolio of products and product candidates.

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

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

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

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

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

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

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

▪ Bayer Agreements – Under Progenics’ April 2016 agreement with a subsidiary of Bayer HealthCare Pharmaceuticals Inc.

(“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 under this agreement.

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 clinical supply agreement with Bayer to include piflufolastat F 18 in Bayer’s clinical trial for prostate cancer.

Bayer will use piflufolastat F 18 to assess PSMA expression levels at baseline and during treatment.

▪ Curium Agreement – We have licensed exclusive rights to Curium to develop and commercialize piflufolastat F 18 in Europe.

Under the terms of the collaboration, Curium is responsible for the development, regulatory approvals and commercialization of piflufolastat F 18 in Europe, and we are entitled to double-digit royalties on net sales of piflufolastat F 18.

Curium is currently conducting a Phase 3 registration trial in Europe for piflufolastat F 18.

▪ FUJIFILM Agreements – In June 2019, EXINI entered into a transfer agreement with FUJIFILM for the rights to aBSI 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 aBSI 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 aBSI and other AI products over the next three years in Japan.

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

In addition, in

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

▪ POINT Biopharma Agreement – In December 2020, we entered into a clinical supply agreement with POINT Biopharma US Inc.

(“POINT Biopharma”) under which we will supply piflufolastat F 18 to POINT Biopharma as an imaging agent to evaluate and follow subjects for a Phase 3 clinical study of POINT Biopharma’s PSMA-targeted metastatic castrate-resistant prostate cancer (“mCRPC”) therapeutic candidate.

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

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

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

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

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

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

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

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

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

▪ RefleXion Agreement – In September 2021, we entered into a development and commercialization collaboration with RefleXion Medical, Inc.

to evaluate the use of piflufolastat F 18 to enable real-time therapeutic guidance of biology-guided radiotherapy in prostate cancer using the RefleXion X1 TM platform.

Under the terms of the agreement, we will contribute to the cost of RefleXion’s registrational program and will share in any upside created by this collaboration.

▪ Regeneron Agreement – In June 2020, we entered into a clinical supply agreement with Regeneron Pharmaceuticals, Inc.

(“Regeneron”) under which we will supply piflufolastat F 18 to Regeneron as an imaging agent to evaluate and follow subjects for a Phase 1/2 clinical study of Regeneron’s anti-PSMAxCD28-targeted mCRPC therapeutic candidate.

In July 2021, we entered into a second agreement with Regeneron under which we will supply piflufolastat F 18 to Regeneron as an imaging agent to evaluate and follow subjects for a Phase 1/2 clinical study of Regeneron’s anti-PSMAxCD3 Bispecific Antibody in mCRPC patients.

▪ ROTOP Agreement – In May 2019, Progenics entered into an exclusive license agreement with ROTOP Pharmaka GmbH (“ROTOP”), a Germany-based developer of radiopharmaceuticals for nuclear medicine diagnostics, to develop, manufacture and commercialize 1404 in Europe.

Under the terms of the license, 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.

◦ Immuno-Oncology - In May 2019, we commenced an initiative to build out our Pharma Services capabilities, which reside in our strategic partnerships and other revenue product category, by entering into a strategic collaboration and license agreement with NanoMab Technology Limited (“NanoMab”), a privately-held biopharmaceutical company focused on the development of next generation radiopharmaceuticals for cancer precision medicine.

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

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

We have undertaken the following efforts to execute that initiative.

◦ Immuno-Oncology - We entered into a strategic collaboration and license agreement with NanoMab Technology Limited (“NanoMab”), a privately-held biopharmaceutical company focused on the development of next generation radiopharmaceuticals for cancer precision medicine.

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

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

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

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

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

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

Under the terms of this agreement, Ratio will drive the early clinical development of NTI-1309.

We are integrating NTI-1309 into our portfolio of imaging biomarkers as part of our Pharma Services offering.

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

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

In April 2021, we announced a strategic collaboration with Allegheny Health Network (“AHN”) which will use our microbubbles in combination with AHN’s ultrasound-assisted non-viral gene transfer technology for the development of a proposed treatment of xerostomia.

Xerostomia is a lack of saliva production leading to dry mouth and has a variety of causes, including radiotherapy and chemotherapy, the chronic use of drugs and rheumatic and dysmetabolic diseases.

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

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

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

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(ii) CarThera SAS (“CarThera”), for the use of our microbubbles in combination with SonoCloud, a proprietary implantable device in development for the treatment of recurrent glioblastoma;

and (iii) Insightec Ltd.

(iii) Insightec Ltd.

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

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

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

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.

In March 2020, we filed an Import Drug License application with the National Medical Products Administration (“NMPA”) for the use of DEFINITY for the echocardiography indication.

In November 2022, we announced the approval of our Import Drug License application with the National Medical Products Administration (“NMPA”) for the use of DEFINITY in patients with suboptimal conventional echocardiography and to better identify the left ventricular endocardial border.

Double-Crane is responsible for obtaining adequate coding, coverage and payment and commercializing DEFINITY in China under a local brand name.

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

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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.

• 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.

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

(“FUJIFILM”) under the name BONENAVI ® .

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

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

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

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

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

(“FUJIFILM”) under the name BONENAVI ® .

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

PYLARIFY AI has demonstrated improved consistency, accuracy and efficiency in quantitative assessment of PSMA PET/CT.

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

The technology analyzes the PET/CT image to segment anatomical regions, including 51 bones and 12 soft tissue organs.

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

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We commercially launched aPROMISE under the name PYLARIFY AI in the U.S.

in November 2021.

FLURPIRIDAZ F 18

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

Under our agreement, GE Healthcare will complete the 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.

in November 2021 and the FDA granted us an additional 510(k) clearance during the second quarter of 2022.

[ 18 F] flurpiridaz

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

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

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

We also have retained 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.

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

GE Healthcare is conducting a second Phase 3 trial and expects to complete enrollment in 2022 and, assuming completion of the Phase 3 trial and regulatory approval, begin commercialization in 2024, although completion, approval and that timing cannot be assured.

• CytoDyn Agreement – Progenics entered into an agreement with CytoDyn Inc.

(“CytoDyn”) in 2012 to sell Progenics’ rights in leronlimab (PRO 140), an investigational humanized monoclonal antibody targeting the CCR5 receptor.

CCR5 appears to act as a human immunodeficiency virus (“HIV”) entry inhibitor and may play a broader role in tumor metastasis and immune-mediated illnesses.

The sale included milestone and royalty payment obligations to Progenics.

Under the 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 has 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.

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

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

Assuming regulatory approval, we anticipate commercialization beginning in 2024.

See Part I, Item 1A.

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Our Clinical Development Candidates

In addition to our commercial products and strategic partnerships with third parties, we also have ongoing clinical development programs that we are currently funding and managing ourselves:

• 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 our multicenter, randomized, controlled, ARROW Phase 2 study in mCRPC.

During 2020, the study was paused to minimize risk to subjects and healthcare providers during the COVID-19 pandemic, and new enrollment in that study restarted in October 2020.

In the fourth quarter of 2021, we completed an interim analysis of the ARROW Phase 2 study.

The Independent Data Monitoring Committee recommended the study continue without modifications.

We currently expect to complete enrollment in the ARROW Phase 2 study later in 2022.

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

We have commenced a Phase 3 clinical trial for the use of LMI 1195 for the diagnosis and management of neuroblastoma tumors in pediatric and adult populations.

We expect to initiate approximately 20 clinical sites in the U.S.

to enroll approximately 100 patients with known or suspected neuroblastoma.

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.

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

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

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

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

PNT2003 is currently in a Phase 3 trial.

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

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

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

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

The primary endpoint in this study is PSA response rate.

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

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

For the years ended December 31, 2022, 2021 and 2020, we invested $311.7 million, $45.0 million and $32.8 million in research and development (“R&D”), respectively, primarily related to our clinical development candidates.

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

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

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Precision Diagnostics

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

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

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

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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

Radiopharmaceutical Oncology

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RELISTOR (methylnaltrexone bromide) Oral Tablet 140 mg United States

With respect to our other products:

With respect to our medical devices:

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

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We launched aPROMISE under the name PYLARIFY AI in the U.S.

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

through a DEFINITY direct sales team.

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

are generated through our direct sales force to hospitals and clinics that maintain their own in-house radiopharmaceutical preparation capabilities, we primarily sell our nuclear imaging products, including TechneLite, NEUROLITE, Xenon, and Cardiolite, to commercial radiopharmacies as described below.

PYLARIFY sales are generated in the U.S.

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

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

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

Sales of DEFINITY are generated in the U.S.

through a DEFINITY direct sales team.

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

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

AZEDRA sales are generated in the U.S.

through an AZEDRA direct sales team.

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

As noted above, in the U.S., we have supply contracts with large radiopharmacy groups, and we sell a majority of our radiopharmaceutical products in our precision diagnostics category to five of these groups—namely Cardinal, Jubilant Radiopharma, formerly known as Triad Isotopes, Inc.

(“Jubilant Radiopharma”), PharmaLogic, RLS and UPPI.

Our contractual arrangements with these radiopharmacy customers generally specify pricing levels and requirements to purchase minimum percentages of certain products during certain periods.

The agreements are generally multi-year arrangements that may be terminated upon the occurrence of specified events, including a material breach by the other party and certain force majeure events.

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

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

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

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

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

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

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

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

• For PYLARIFY, our competitors currently include Telix Pharmaceuticals Limited’s Illuccix (gallium-68 PSMA-11 injection), a PSMA PET imaging agent approved by the FDA for commercialization in December 2021, and Bracco’s Axumin (fluciclovine F 18), a PET imaging agent.

In addition, the University of California, San Francisco and the University of California, Los Angeles have approved NDAs for a gallium-68 PSMA-11 injection for PSMA PET imaging, which we believe will primarily be used within their hospital systems.

We also face potential competition from Novartis AG, which has a gallium-68 PSMA-11 kit for PET imaging currently under review with the FDA, and Bracco, which has an F 18 PSMA PET imaging agent in late stage clinical development;

we believe that one or both of the Novartis and Bracco PSMA agents could be approved by the FDA for commercialization later in 2022 or in 2023.

• For RELISTOR, our principal competitors include RedHill Biopharma Inc.;

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

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

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

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

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

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

POINT Biopharma;

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

Telix Pharmaceuticals Limited;

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

• For LMI 1195, our principal competitors may include GE Healthcare’s iobenguane 123 injection.

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

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

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

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

In addition, distributors of our products could attempt to shift end-users to competing diagnostic

modalities and products, or bundle the sale of a portfolio of products, to the detriment of our specific products.

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.

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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 March 31, 2022, and we are actively negotiating an extension.

Despite our globally diverse Mo-99 suppliers, we still face supplier and logistical 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 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.

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.

The NTP Agreement expires on December 31, 2024.

Although we have a globally diverse Mo-99 supply with IRE in Belgium, NTP in South Africa, and ANSTO in Australia, we still face supplier and logistical challenges in our Mo-99 supply chain.

When one supplier experiences outages, we generally rely on Mo-99 supply from the other suppliers to limit the impact of the outages.

We believe we effectively 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.

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

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

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

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

However, we cannot assure you that our arrangement with SHINE will

result in commercial quantities of Mo-99 for our business, or that SHINE together with our current suppliers will be able to deliver a sufficient quantity of Mo-99 to meet our needs.

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

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

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

We receive Iodine 131 from IRE in Belgium and we are in the process of securing a secondary source.

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

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

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Manufacturing

We maintain manufacturing operations at our North Billerica, Massachusetts facility.

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 on a hot cell line.

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

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

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

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

The commercial manufacture of PYLARIFY required us to create a field-based network of specialized PMFs with radioisotope-producing cyclotrons.

The radioisotope used in PYLARIFY is F 18, which has a 110 minute half-life, requiring that this agent 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 PYLARIFY.

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

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

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

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

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

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

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

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

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

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

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.

To ensure the quality of the products that are manufactured by third parties, the key raw materials used in those products are first sent to our North Billerica, Massachusetts facility, where we test them prior to the third party manufacturing of the final product.

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

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

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

The commercial manufacture of PYLARIFY required us to create a field-based network of specialized PMFs with radioisotope-producing cyclotrons.

The radioisotope used in PYLARIFY is F 18, which has a 110 minute half-life, requiring that this agent 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 PYLARIFY.

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

Because each of the PMFs manufacturing PYLARIFY is deemed by the FDA to be a separate manufacturing site, each requires separate FDA approval, and we can give no assurance that the FDA will continue to approve PMFs in accordance with our planned roll-out schedule for PYLARIFY, particularly given ongoing challenges of the COVID-19 pandemic.

Flurpiridaz F 18, if approved by the FDA, will have a manufacturing and PMF approval process similar to PYLARIFY.

Manufacturing and Supply Arrangements

We currently have the following technology transfer and manufacturing and supply agreements in place for some of our major products:

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

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

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

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

• PYLARIFY —The commercial manufacture of PYLARIFY required us to create a field-based network of specialized PMFs with radioisotope-producing cyclotrons.

In preparation for our commercial launch, we entered into commercial supply agreements with different radiopharmacy networks.

Under our supply agreements, the PMF manufactures the radioisotope F 18 on a cyclotron, and then combines the F 18 with certain chemical ingredients in specially designed chemistry synthesis boxes to manufacture PYLARIFY.

The finished PYLARIFY is then quality control tested and transferred to the PMF’s radiopharmacist who prepares and dispenses patient-specific doses from the final product.

See Part I, Item 1A.

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Competitors also may harm our sales by designing products that mirror the capabilities of our products or technology without infringing our intellectual property rights.

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

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

Trademarks, Service Marks and Trade Names

We own various trademarks, service marks and trade names, including, among others, AZEDRA, AZEDRA Service Connection, Cardiolite, DEFINITY, DEFINITY RT, EXINI, Find, Fight and Follow, Find > Fight > Follow, Lantheus, Lantheus Medical Imaging, LUMINITY, Molecular Insight, NEUROLITE, Progenics, Progenics Pharmaceuticals, PYLARIFY, PYLARIFY AI, TechneLite, VIALMIX and VIALMIX RFID.

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

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

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

and/or numerous foreign jurisdictions.

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We also rely upon trade secrets and contracts to protect our proprietary information.

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

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

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

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

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

and internationally.

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

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

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

and internationally.

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

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

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

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We can give no assurance that we would have grounds to file a patent infringement suit, that we would obtain the full 30 month stay, that we would be successful on the merits asserting that an Applicant infringes our Orange Book-listed patent, or that we would be successful defending the validity or enforceability of our Orange Book-listed patent in court or in a USPTO adversarial proceeding.

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

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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.

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

and internationally.

for PYLARIFY, we have four Orange Book-listed patents, including composition of matter patents which expire in 2030 and 2037.

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

PYLARIFY AI - U.S.

Patents and pending patent applications worldwide relating to automated medical image analysis, have expiration ranges from 2037 to 2041.

Patents and pending patent applications worldwide relating to automated medical image analysis, have expiration ranging from 2037 to 2041.

Other Nuclear Products - Neither CARDIOLITE nor NEUROLITE is covered any longer by patent protection in either the U.S.

or the rest of the world.

Xenon, Thallium and Gallium have no patent protection;

however, we have patent protection in the U.S.

We have patent protection in the U.S.

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

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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.

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

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

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

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

While certain of those patents, and associated license, have already expired, a patent relating to alternative approaches for preparing AZEDRA (not currently implemented) expires worldwide in 2022 and 2024.

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

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

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

a manufacturing method expiring in 2035.

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

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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.

Further, we own a U.S.

patent and have patent applications that are pending in the U.S.

and worldwide relating to aBSI improvements, which have expiration ranging from 2040 to 2041.

flurpiridaz - 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.

PNT-2002 - We exclusively license granted U.S.

patents and pending U.S.

patent applications as well as pending patent applications in jurisdictions outside of the U.S.

directed to formulations, use and manufacturing of PNT-2002.

The granted U.S.

patents expire in 2041.

PNT-2003 - We exclusively license pending U.S.

patent applications as well as pending patent applications in jurisdictions outside of the U.S.

directed to formulations, use and manufacturing of PNT-2003 which, if granted, would expire in 2041.

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

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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.

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

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.

PSMA 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.

We seek to protect our proprietary information, in part, using confidentiality agreements with our collaborators, employees, consultants and other third parties and invention assignment agreements with our employees.

These confidentiality agreements may not prevent unauthorized disclosure of trade secrets and other proprietary information, and we cannot provide assurances that an employee or an outside party will not make an unauthorized disclosure of our trade secrets, other technical know-how or proprietary information.

We may not have adequate monitoring abilities to discover, or adequate remedies for, any unauthorized disclosure.

This might happen intentionally or inadvertently.

It is possible that a competitor will make use of such information, and that our competitive position will be compromised, in spite of any legal action we might take against persons making such unauthorized disclosures.

In addition, our trade secrets may otherwise become known or be independently discovered by competitors.

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 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 on the PYLARIFY patent family from Johns Hopkins University (“JHU”) and on the patent rights on RELISTOR from Wyeth LLC.

Some of these licenses are material to our business – for example, the licenses on the PYLARIFY patent family from Johns Hopkins University (“JHU”).

See Part I, Item 1A.

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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.

Under Section 529 of the FDCA, companies that develop new drugs for the prevention and treatment of certain rare pediatric diseases may be eligible for a rare pediatric disease priority review voucher for a subsequent human drug application.

The voucher is only granted if the drug is approved for the rare pediatric disease, but once granted, the voucher can either be used by the recipient or sold to a third party, typically a large pharmaceutical or related company that seeks priority review for an unrelated drug it expects will generate substantial revenue.

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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On August 9, 2021, the FDA announced that, as part of its implementation of this court decision, the FDA intended to regulate products that meet both the device and drug definition as devices, except where Congress intended a different classification.

The FDA further indicated that it intended to bring previously classified products into line with the court decision and would reexamine whether individual imaging agents meet the device definition.

In connection with its announcement, the FDA requested comments from the industry on five topics:

categories of products implicated by the court decision;

the transition process;

the transition timing;

user fee transitions;

and determining drug or device status.

We submitted comments to the FDA in response to its request for comments.

While we question whether the FDA has authority to make this change, we believe that pre-existing law already establishes that a broad spectrum of imaging agents have already been established by Congress to be “drugs”, and do not believe that any of our imaging agents meets the definition of a “device” under the FDCA.

We can give no assurance that the FDA will agree with our position.

In addition, if the FDA determines that one or more of our imaging agents meet the definition of a “device”, we do not know when such reclassification would be effective, how any transition rules would be formulated or applied, and whether or not the legal framework provided by the Hatch-Waxman Act described below would be preserved for some time after such reclassification.

A reclassification of one or more of our imaging agents as a “device” could have a material adverse effect on our business, results of operations, financial condition and cash flows.

The FDA further indicated that it intended to bring previously classified products into line with the court decision and would reexamine whether individual imaging agents meet the device definition, which raised uncertainty as to how our some of our products would be regulated.

Congress subsequently resolved this issue when it passed the Consolidated Appropriations Act of 2023, which amended the FDCA by adding a provision that deemed any contrast agent or radioactive drug to be a drug.

Because our operations include the manufacture and distribution of medical radioisotopes and other medical products, we are subject to regulation by the NRC and the departments of health of each state in which we operate and the applicable state boards of pharmacy.

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Third-party payors in the U.S.

include commercial payors, including managed care providers, and State and Federal healthcare programs, such as Medicare and Medicaid.

include private payors, including managed care providers, and State and Federal healthcare programs, such as Medicare and Medicaid.

The process for determining whether a payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product.

Coverage of a product does not ensure there will be an appropriate reimbursement amount for such product and the process to ensure appropriate reimbursement is outside our control.

For commercial payors, coverage and reimbursement of our products vary from commercial payor to commercial payor.

Many commercial payors, such as managed care providers, manage access to products, and may use medical policies (which may include specific coverage requirements such as prior authorization, re-authorization and achieving performance metrics under value-based contracts) to control utilization.

For private payors, coverage and reimbursement of our products vary from private payor to private payor.

Many private payors, such as managed care providers, manage access to products, and may use medical policies (which may include specific coverage requirements such as prior authorization, re-authorization and achieving performance metrics under value-based contracts) to control utilization.

Exclusion from or restriction in coverage can reduce product use.

For government payors, we participate, as required, in the Federal Supply Schedule (FSS) and the PHS 340b program, which each require discounts for participation and may be subject to change.

For government payors, we participate, as required, in the Medicaid drug rebate program, the Federal Supply Schedule (FSS) and the Public Health Service Act 340B program, which each require discounts for participation and may be subject to change.

For Medicare, reimbursement to customers for our products is generally established through the rulemaking process or in discussion with Medicare Administrative Contractors (MACs).

We have ongoing conversations with third-party payors to advocate for appropriate coding, coverage and payment for our portfolio of products, but we can give no assurance that adequate coding, coverage and payment can be obtained from such commercial or government payors.

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

Medicare Outpatient Pass-Through Payment Status

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

The reimbursement rate for PYLARIFY is based on the wholesale acquisition cost (WAC) plus three percent until CMS can establish an ASP for the product, which could take six months.

Once CMS establishes an ASP, the add-on percentage applicable to PYLARIFY will likely vary.

PYLARIFY has been assigned Healthcare Common Procedure Coding System code A9595 (piflufolastat F 18, diagnostic, 1 millicurie) for identification in claims and can be used by both public and commercial payors.

Under existing Medicare Part B payment policy, non-pass-through diagnostic radiopharmaceuticals are not separately paid and are instead packaged into payment for the underlying procedure.

Therapeutic radiopharmaceuticals, however, continue to be eligible for separate payment even after expiration of pass-through status.

We plan to continue our advocacy efforts with CMS and private insurers so that PYLARIFY customers will have appropriate and adequate reimbursement following the expiration of pass-through status, although we can give no assurances that we will be successful in those efforts.

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

In 2022, CMS established an ASP for PYLARIFY and reimbursed at a rate equal to ASP plus an add-on percentage that varied throughout the year.

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

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

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

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

Healthcare Reform and Other Laws Affecting Payment

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The Healthcare Reform Act has been subject to political and judicial challenges, but it has generally withstood such challenges, and the main provisions of the Healthcare Reform Act remain in effect.

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

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.

For instance, Congress is currently considering the Build Back Better Act, which contains many drug pricing provisions that could adversely affect our business, including but not limited to authorization for Medicare to directly negotiate pricing for high-cost drugs, and inflation penalties for Part B and D drugs with price increases greater than the rate of inflation.

To be clear, changes could occur at the federal level or state level and may be adopted by statute, rule, or sub-regulatory policies.

More recently, Congress enacted the Inflation Reduction Act of 2022 (the “IRA”) which significantly impacts the pharmaceutical industry.

Among other provisions, the IRA authorizes Medicare to negotiate pricing for the highest Medicare-spend drugs, as determined by their Medicare Part B and D spend, that have been on the market for an extended period of time without market competition.

Although the IRA provides for a limited number of categorical exclusions from Medicare negotiation, radiopharmaceuticals are not among those categorical exclusions.

CMS plans to begin implementing the first year of Medicare negotiation, which will be restricted to Part D drugs, starting in calendar years 2026 and 2027.

We are currently focused on drugs that are covered under Part B, therefore we do not expect the Part D benefit redesign to have an impact on our portfolio.

Part B drugs will be considered for Medicare negotiation beginning in calendar year 2028, and CMS will begin the process of identifying Part B drugs for negotiation as early as calendar year 2026.

We are monitoring the implementation of the IRA to determine what impact, if any, this would have on our current products and product candidates in development.

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

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

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

Recent state legislative efforts seek to address drug costs and generally have focused on increasing transparency around drug costs or limiting drug prices.

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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, the Consolidated Appropriations Act 2021 subsequently extended this suspension until March 31, 2021, and Congress further extended the suspension through March 31, 2022.

The imposition of the 2% payment adjustment had been suspended through March 31, 2022 and went into effect as of April 1, 2022.

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

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

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

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

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

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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

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

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.

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

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

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

In particular, we must maintain a nuclear byproducts materials license issued by the Commonwealth of Massachusetts.

3 unchanged sentences

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

As of December 31, 2021 and 2020, we have a liability recorded associated with the fair value of the asset retirement obligations of $20.8 million and $14.0 million, respectively.

As of December 31, 2022 and 2021, we have a liability of approximately $22.5 million and $20.8 million, respectively associated with our asset retirement obligations.

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

4 unchanged sentences

(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;

(iii) updating our snow removal plan at our North Billerica campus 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.

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

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

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

8 unchanged sentences

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

During 2021, we hired additional employees to assist us with the commercialization of PYLARIFY, including in sales, marketing, reimbursement, quality and medical affairs.

In addition, we hired a Chief Human Resources Officer to help us attract, develop and retain leading and diverse talent in business-critical roles.

Diversity, Inclusion, Ethics and Compliance

2 unchanged sentences

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

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

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

17 unchanged sentences

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

With respect to the COVID-19 pandemic, we operated 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.

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

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

Corporate History

16 unchanged sentences

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