Lantheus Holdings, Inc. (‘Lantheus’) operates as a radiopharmaceutical-focused company.
The company is delivering life-changing science to enable clinicians to Find, Fight, and Follow disease to deliver better patient outcomes. The company classifies its products into three categories: Radiopharmaceutical Oncology, Precision Diagnostics, and Strategic Partnerships and Other Revenue. The company’s leading Radiopharmaceutical Oncology products help healthcare professionals (‘HCPs’) Find, Fight, a...
Lantheus Holdings, Inc. (‘Lantheus’) operates as a radiopharmaceutical-focused company.
The company is delivering life-changing science to enable clinicians to Find, Fight, and Follow disease to deliver better patient outcomes. The company classifies its products into three categories: Radiopharmaceutical Oncology, Precision Diagnostics, and Strategic Partnerships and Other Revenue. The company’s leading Radiopharmaceutical Oncology products help healthcare professionals (‘HCPs’) Find, Fight, and Follow cancer. The company’s leading Precision Diagnostic products assist HCPs to Find and Follow diseases, with a focus on cardiology. The company’s Strategic Partnerships include biomarkers and digital solutions in the support of its partners’ therapeutic development, out-licensing agreements for non-core assets, and optimization of its assets geographically.
The company’s 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. The company’s diagnostic products provide 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.
The company produces and markets its products throughout the United States (the ‘United States’ or the ‘U.S.’), selling primarily to hospitals, independent diagnostic testing facilities, and radiopharmacies. The company sells its products outside the U.S. through a combination of direct distribution in Canada and third-party distribution relationships in Europe, Canada, Australia, the Asia-Pacific, Central America, and South America.
Acquisition of NAV-4694
On June 18, 2024, the company acquired Meilleur Technologies, Inc. (‘Meilleur’), including its asset NAV-4694, an investigational F-18-PET imaging agent that targets beta amyloids in Alzheimer’s disease. Research revenue is derived from partnerships with pharmaceutical companies and academic institutions that use NAV-4694 in clinical trials.
Exclusive License for Radiopharm Theranostics Limited
On June 15, 2024, the company entered into an agreement with Radiopharm to acquire all of Radiopharm’s global, exclusive rights to two licensed preclinical assets (the ‘Radiopharm Asset Purchase’). The company acquired global, exclusive rights to both a monoclonal antibody that targets LRRC15, a preclinical therapeutic candidate targeting osteosarcoma, and a Trophoblast cell surface antigen 2 (‘TROP2’)-targeted nanobody, a preclinical stage therapy. In connection with this acquisition, the company is assuming the underlying license agreements related to the two preclinical assets, together with their respective milestone and royalty payment obligations.
Strategic Agreements with Perspective Therapeutics, Inc.
On January 8, 2024, the company entered into multiple strategic agreements with Perspective, a radiopharmaceutical company that is pursuing advanced treatment applications for cancers throughout the body. Under the agreements, the company obtained an option to exclusively license Perspective’s Pb212-VMT-Alpha-NET, a clinical stage alpha therapy in development for the treatment of neuroendocrine tumors, and an option to co-develop certain early-stage therapeutic candidates targeting prostate cancer using Perspective’s innovative platform technology.
On March 1, 2024, the company transferred the fixed assets and associated lease of its Somerset, New Jersey facility to Perspective, and the parties entered into a transition services arrangement pursuant to which the company provided certain services relating to the final disposal of radioactive waste and certain other related services.
Exclusive License for PNT2002 & PNT 2003
On December 20, 2022, the company announced the closing of a set of strategic collaborations with POINT Biopharma Global Inc. (‘POINT’), in which the company was granted a license to exclusive worldwide rights (excluding Japan, South Korea, China (including Hong Kong, Macau, and Taiwan), Singapore, and Indonesia) to co-develop and commercialize POINT’s PNT2002 and PNT2003 product candidates. PNT2002 is a PSMA-targeted radiopharmaceutical therapy in development for the treatment of metastatic castration-resistant prostate cancer (‘mCRPC’). PNT2003 is a somatostatin receptor (‘SSTR’) therapy with non-carrier added lutetium-177, which is in registration to treat patients with SSTR-positive neuroendocrine tumors.
On December 27, 2023, Lilly announced the completion of its acquisition of POINT. The acquisition has not impacted the status of the license agreements related to these product candidates or the work being performed in connection with those license agreements and the company’s collaboration with POINT.
PNT2002
POINT is generally responsible for funding and development activities required for FDA approval of PNT2002, including generating all clinical and nonclinical data, analysis, and other information, and the company is responsible for preparing for and seeking regulatory approval, as well as performing and funding all future development and commercialization following such approval. POINT will be responsible for all manufacturing of PNT2002, subject to certain exceptions described in the license and collaboration agreement between the company and POINT, dated November 11, 2022 (the ‘PNT2002 License Agreement’).
The Phase 3 registrational clinical trial for PNT2002 (‘SPLASH’) was designed to evaluate the efficacy and safety of PNT2002 in patients with mCRPC who have progressed following treatment with an androgen receptor pathway inhibitor (‘ARPI’). On December 18, 2023, the company announced that the SPLASH trial met its primary endpoint, demonstrating a median radiographic progression-free survival (‘rPFS’) per blinded independent central review of 9.5 months for patients treated with PNT2002, compared to 6 months for patients treated with ARPI in the control arm, a statistically significant 29% reduction in the risk of radiographic progression or death (hazard ratio (‘HR’) 0.71; p=0.0088). At the time of the analysis, interim overall survival (‘OS’) results were immature (46% of protocol pre-specified target OS events reached), and the HR was 1.11. On September 15, 2024, the company presented additional clinical data from initial topline results of SPLASH during the European Society of Medical Oncology Congress 2024. On November 6, 2024, the company announced that the second interim analysis performed at 75% of protocol pre-specified overall survival events demonstrated results for both rPFS and OS that did not materially change from the interim analysis that was performed at 46% of pre-specified events. The OS results and HR in the intent-to-treat population remain confounded by the overwhelming number of patients who crossed over to receive PNT2002. Crossover adjusted analyses were post-hoc, and the company is continuing to review the data and perform additional subset analyses in collaboration with its partner in preparation for further interactions on its path forward.
PNT2002 demonstrated a favorable safety profile compared to patients treated with ARPI in the control arm. Only 3.0% of patients treated with PNT2002 halted or reduced therapy as a result of treatment-emergent adverse events (‘TEAEs’), compared to 11.5% of patients treated with ARPI, and 17.1% of PNT2002 patients experienced serious TEAEs compared to 23.1% of ARPI patients.
The open-label study randomized 412 patients with PSMA-expressing mCRPC who had progressed on ARPI therapy and either refused or were not eligible for chemotherapy, in a 2:1 randomization ratio. At the time of the first interim analysis, 84.6% of patients who experienced progressive disease in the control arm subsequently crossed over to receive PNT2002. SPLASH was conducted across the United States, Canada, Europe, and the United Kingdom. Eighty percent of SPLASH patients resided in North America, and approximately ten percent of all participants were Black or African American.
In June 2024, Endocyte, Novartis, and Purdue Research Foundation sued POINT and Lilly alleging that POINT’s manufacturing and sale of PNT2002 infringes an Endocyte patent.
PNT2003
POINT is responsible for curating all data, analysis, and other information necessary for regulatory approval and supporting the company in the preparation of regulatory filings for PNT2003. The company is responsible for preparing for and seeking regulatory approval of all such applications, as well as performing and funding all future development and commercialization following such approval. POINT will be responsible for all manufacturing of PNT2003, subject to certain exceptions described in the license and collaboration agreement between the company’s subsidiary, Lantheus Three, and POINT, dated November 11, 2022 (the ‘PNT2003 License Agreement’).
On January 11, 2024, the company announced that its Abbreviated New Drug Application (‘ANDA’) for PNT2003 had been accepted for filing by the FDA. On January 26, 2024, the company was sued in the District Court for the District of Delaware by Advanced Accelerator Applications USA, Inc. and Advanced Accelerator Applications SA, each a Novartis entity, for patent infringement in response to its ANDA filing and Paragraph IV certification, consistent with the process established by the Hatch-Waxman Act. Under the terms of the Hatch-Waxman Act, full FDA approval of its ANDA filing could be subject to a stay of up to 30 months. If the company’s filing is stayed for the full 30-month period, and the company is successful in obtaining FDA approval, the company would expect to launch PNT2003 in 2026, although there can be no assurance of that approval or timing. Based on the most recent update to the FDA’s online Paragraph IV database listings, the company is the first applicant to have filed a substantially complete ANDA for lutetium Lu 177 dotatate containing a Paragraph IV certification under the provisions of the Hatch-Waxman Act. The company defines radioequivalent as a radiopharmaceutical whose mechanism of action is determined to be equivalent to that of the reference product by the FDA, or a similar regulator outside the United States.
Portfolio of Commercial Products and Other Sources of Revenue
Radiopharmaceutical Oncology
The company’s commercial product in its Radiopharmaceutical Oncology category includes the following:
PYLARIFY (also known as piflufolastat F-18, 18F-DCFPyL, or PyL) is an F-18-labelled PSMA-targeted PET imaging agent used with PET/computed tomography (‘CT’). PYLARIFY is indicated in the U.S. for PET imaging of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy and in men with suspected recurrence based on elevated serum prostate-specific antigen (‘PSA’) levels. Piflufolastat F-18 is approved under the name PYLCLARI in Europe and licensed by the company to Curium.
Precision Diagnostics
The company’s commercial products in its Precision Diagnostics category include the following:
DEFINITY is an injectable ultrasound enhancing agent with perflutren-containing lipid microspheres, or microbubbles, that is used in echocardiography exams. The indication for DEFINITY in the U.S. is for use in adult and pediatric patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. DEFINITY is approved under the name LUMINITY in Europe and sold through third-party distribution relationships.
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. TechneLite uses Molybdenum-99 (‘Mo-99’) as its active ingredient.
NEUROLITE is an injectable, Tc-99m-labeled imaging agent used with single-photon emission computed tomography (‘SPECT’) technology to identify the area within the brain where blood flow has been blocked or reduced due to stroke.
Xenon-133 (‘Xenon’) is a radiopharmaceutical gas that is inhaled and used to assess pulmonary function and also to image cerebral blood flow. Xenon is manufactured by a third party as a by-product of Mo-99 production and is processed and finished by the company.
CARDIOLITE, also known by its generic name sestamibi, is an injectable, Tc-99m-labeled imaging agent used in myocardial perfusion imaging (‘MPI’) procedures to assess blood flow to the muscle of the heart using SPECT. Included in CARDIOLITE revenues are branded CARDIOLITE and generic sestamibi revenues.
Strategic Partnerships and Other Revenue
The company’s commercial products in its Strategic Partnerships and Other Revenue product category include the following:
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 received a European Conformity Marking (‘CE mark’).
aPROMISE, or PYLARIFY AI, is artificial intelligence medical device software that is designed to allow HCPs and researchers to perform standardized quantitative assessment of PSMA PET/CT images in prostate cancer, including those images obtained by using PYLARIFY.
The company’s Strategic Partnerships and Other Revenue also include revenue derived from partnerships with pharmaceutical companies and academic institutions that use its investigational products, such as MK-6240 and NAV-4694, in clinical trials as research tools, as well as royalties and other milestone payments received from its strategic partners that have commercialized products pursuant to license arrangements with the company. For example, flurpiridaz is an F-18-based PET MPI agent that the company previously licensed to GE Healthcare Limited (‘GE Healthcare’). Flurpiridaz was approved by the FDA in 2024 under the name Flyrcado for PET MPI under rest or stress (pharmacologic or exercise) in adult patients with known or suspected coronary artery disease (‘CAD’) to evaluate for myocardial ischemia and infarction. Similarly, RELISTOR (methylnaltrexone bromide) is a treatment for opioid-induced constipation that decreases the constipating side effects induced by opioid pain medications such as morphine and codeine without diminishing their ability to relieve pain. RELISTOR is approved in two forms: a subcutaneous injection and an oral tablet. In 2011, Progenics licensed methylnaltrexone (‘MNTX’) along with products containing MNTX, including both approved forms of RELISTOR, to Salix Pharmaceuticals, Inc., a Bausch Health Companies, Inc. (‘Bausch’), and on August 2, 2023, the company sold the right to the RELISTOR net sales royalties under that license agreement and retained the rights to future sales-based milestone payments.
Radiopharmaceutical Oncology
PYLARIFY is the most utilized radiopharmaceutical diagnostic agent indicated for PET imaging of PSMA-positive lesions in patients with prostate cancer with suspected metastasis who are candidates for initial definitive therapy and in patients with suspected recurrence based on elevated PSA levels. PYLARIFY works by binding to PSMA, a protein that is overexpressed on the surface of more than 90% of primary and metastatic prostate cancer cells. PYLARIFY works with PET/CT technology to produce a combined scan that enables the scan reader to detect and locate the disease.
PYLARIFY is manufactured on a diverse, F-18 distributor supply network of PMFs, ensuring convenient and reliable supply. After being made on a cyclotron at a PMF, the F-18 is then combined with certain chemical ingredients in specially designed chemistry synthesis boxes to manufacture PYLARIFY. The finished PYLARIFY is then quality control tested and transferred to a radiopharmacist who prepares and dispenses patient-specific doses of the final product. Because each PMF manufacturing PYLARIFY is deemed by the FDA to be a separate manufacturing site, each is separately approved by the FDA. As of December 31, 2024, the company had activated a total of 62 PMF manufacturing sites in its PMF network. These additional sites provide geographic breadth, out-the-door time flexibility, and added optionality. Overall, the company has achieved broad national distribution of PYLARIFY with customers in 48 of 50 states, the District of Columbia, and Puerto Rico.
In addition to the company’s network of commercial PMFs, the company also works with academic medical centers in the U.S. that have radioisotope-producing cyclotrons and that have expressed an interest in manufacturing PYLARIFY. For this initiative, the company enters 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.
The company’s Healthcare Procedure Coding System code, which enables streamlined billing, went into effect as of January 1, 2022. In addition, effective January 1, 2022, the Centers for Medicare and Medicaid Services (‘CMS’) granted transitional pass-through payment status (‘TPT Status’) in the hospital outpatient setting for PYLARIFY, enabling traditional Medicare fee-for-service (‘FFS’) to provide separate payment for PYLARIFY in addition to the payment for the PET/CT procedure in that setting. TPT Status for PYLARIFY expired on December 31, 2024.
In November 2024, CMS released the final rule for its calendar year 2025 Medicare Hospital Outpatient Prospective Payment System (the ‘CMS 2025 OPPS Rule’), which recognizes the value and need for broad access in diagnostic radiopharmaceuticals. The rule provides separate payment for those diagnostic radiopharmaceuticals with per day costs greater than $630. Effective January 1, 2025, CMS is maintaining separate payment for PYLARIFY after the expiration of TPT Status for the approximately 20% of patients with traditional Medicare FFS insurance coverage who are treated in the hospital outpatient setting. The calendar year 2025 payment rate for PYLARIFY is listed in Addendum B of the final rule. The company plans to continue working with CMS on the potential adoption of payment based on Average Sales Price (‘ASP’) in the future. The company has been reporting ASP since its first dose sold, helping to provide a clear path forward for CMS to potentially make payments based on ASP instead of mean unit cost (‘MUC’).
The company’s continued growth of PYLARIFY will depend on its ability to clinically and commercially differentiate PYLARIFY from other products on the market and to maintain PYLARIFY as the most utilized PSMA PET imaging agent in a competitive space. PYLARIFY’s current competition is primarily two Gallium-68 (‘Ga-68’)-based PSMA imaging agents, an F-18-based PSMA imaging agent, and other non-PSMA-based imaging agents commonly referred to as conventional imaging. The potential for future generic entrants to the market as a result of the expiry of PYLARIFY’s five-year new chemical entity (‘NCE’) exclusivity period in 2026, on the fifth anniversary of the FDA’s approval, could generate increased competition for PYLARIFY. Continued growth and revenue contribution from PYLARIFY will also depend on the company’s ability to differentiate PYLARIFY, including through flexible and dependable access to PYLARIFY nationally, a best-in-class customer experience, and through long-term strategic contracts.
The company actively pursues patents in connection with PYLARIFY, both in the U.S. and internationally. In the U.S. for PYLARIFY, the company has patents listed in the FDA’s publication, ‘Approved Drug Products with Therapeutic Equivalence Evaluations’ (the ‘Orange Book’), including composition of matter patents, the last of which expires in 2037. Outside of the U.S., the company has, and is pursuing, additional patents related to piflufolastat F-18 to obtain similar patent protection as in the U.S.
Precision Diagnostics
DEFINITY is the most utilized ultrasound enhancing agent in the U.S. and is indicated for use in adult and pediatric patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. The term DEFINITY refers to both its activated and non-activated forms.
DEFINITY is a clear, colorless, sterile liquid that, upon activation in a VIALMIX or VIALMIX RFID, medical devices specifically designed for DEFINITY, becomes a homogenous, opaque, milky white injectable suspension of perflutren-containing lipid microspheres. After activation and intravenous injection, DEFINITY opacifies the left ventricular chamber and improves the delineation of the left ventricular endocardial border, or innermost layer of tissue that lines the chamber of the left ventricle. Better visualization of the left ventricle allows clinicians to make more informed decisions about disease status.
Since its launch in 2001, DEFINITY has been used in imaging procedures in more than 28 million echocardiograms throughout the world. In March 2024, the company received FDA approval for its supplemental new drug application for the use of DEFINITY in pediatric patients with suboptimal echocardiograms. The FDA decision was based on usage data from three pediatric clinical trials conducted with DEFINITY. The company estimates that, as of December 31, 2024, DEFINITY had over 80% share of the U.S. segment for ultrasound enhancing agents in echocardiography procedures. DEFINITY competes with two other FDA-approved ultrasound enhancing agents, as well as echocardiography without the use of ultrasound enhancing agents and non-echocardiography imaging modalities. DEFINITY and the other FDA-approved ultrasound enhancing agents all carry an FDA-required boxed warning, which has been modified over time, to notify physicians and patients about potentially serious safety concerns or risks posed by the products.
The company continues to actively pursue additional patents in connection with DEFINITY, both in the U.S. and internationally. In the U.S. for DEFINITY, the company has Orange Book-listed method-of-use patents, the last of which expires in 2037, as well as additional manufacturing patents that are not Orange Book-listed expiring in 2037. The Orange Book-listed patents include a patent on the use of VIALMIX RFID, which expires in 2037; the company has submitted additional VIALMIX RFID patent applications in major markets throughout the world.
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. The company relies on Jubilant HollisterStier (‘JHS’) as a significant supplier of DEFINITY. The company also produces DEFINITY in its in-house manufacturing facility at its North Billerica campus.
TechneLite
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 sourced in its supply chain in nuclear research reactors located in Belgium, South Africa, and Australia from enriched uranium. The TechneLite generator houses a vertical glass column at its core that contains Mo-99, which degrades to Tc-99m. During the company’s manufacturing process, Mo-99 is added to the column within the generator where it is adsorbed onto alumina powder. The column is sterilized, enclosed in a lead shield, and further sealed in a cylindrical plastic container, which is then immediately shipped to the company’s radiopharmacy customers. Because of the half-lives of Mo-99 and Tc-99m, radiopharmacies typically purchase TechneLite generators on a weekly basis pursuant to standing orders.
TechneLite is 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.
Strategic Partnerships and Other Revenue
The company continues to seek ways to further increase the overall value of its products and product candidates. In addition to the company’s recently announced plans to acquire Life Molecular and Evergreen, the company is evaluating a number of different opportunities to collaborate, in-license, or acquire additional products, product candidates, businesses, and technologies to drive its future growth. In particular, the company is focused on radiopharmaceutical diagnostic and therapeutic product opportunities in oncology, neurology, and other strategic areas that complement its existing portfolio. The company’s Biomarker Solutions business focuses on advancing innovative imaging biomarker solutions, such as its investigational late-stage Alzheimer’s disease radiodiagnostic candidates, MK-6240 and NAV-4694, through collaborations with pharmaceutical companies and academic centers.
The company’s Biomarker Solutions business also includes its Microbubble Platform, in which the company generally enters into collaborations with partners seeking to include its microbubble as part of a kit used with its partner’s medical device for therapeutic applications. In these collaborations, its microbubble is generally intended to be used as a vehicle to deliver a therapeutic drug. The company’s Digital Solutions business focuses on developing and commercializing 510(k) cleared and CE marked digital applications to enhance the performance of imaging agents; its Digital Solutions portfolio includes aBSI, aPROMISE, and PYLARIFY AI.
Oncology
As the company continues to pursue expanding strategic partnerships, its Biomarker Solutions activities in oncology include:
Prostate Cancer – The company collaborates with pharmaceutical companies developing therapies and diagnostics in prostate cancer.
Curium (the company’s licensee for piflufolastat F-18 in Europe) is commercializing piflufolastat F-18 under the name PYLCLARI in Europe. In addition, the company previously entered into an agreement with Curium to add PYLARIFY to its U.S. ECLIPSE trial, a multi-center, open-label, randomized Phase 3 trial comparing the safety and efficacy of Curium’s PSMA-targeted therapeutic versus hormone therapy in patients with mCRPC. PYLARIFY is being used to determine PSMA-avidity as part of patient selection.
The company has also entered into several other separate agreements, including with POINT and Regeneron Pharmaceuticals, Inc., under which the company supplies PYLARIFY in connection with their clinical trials. Under a strategic collaboration with the Prostate Cancer Clinical Trial Consortium (‘PCCTC’), a premier multicenter clinical research organization that specializes in prostate cancer research, the company’s artificial intelligence (‘AI’) platform is being integrated into PCCTC studies to advance the development and validation of novel AI-enabled biomarkers.
Pan-Oncology - In collaboration with Ratio Therapeutics LLC (previously Noria Therapeutics, Inc.), the company is developing LNTH-1363S, a novel copper-64 labeled PET imaging agent, targeting fibroblast activation protein alpha. In 2024, the company completed a Phase 1 study for LNTH-1363S to evaluate the pharmacokinetics, biodistribution, and radiation dosimetry in adult healthy volunteers and initiated a Phase 1/2a study.
Microbubble Platform
The company previously entered into microbubble collaborations with strategic partners that are using its microbubbles in connection with the development of their medical devices. For example, CarThera SAS is developing SonoCloud, a proprietary implantable device in development for the treatment of recurrent glioblastoma that will be used in combination with its microbubbles. Similarly, Insightec Ltd. is developing a transcranial guided focused ultrasound device for the treatment of glioblastoma, as well as other neurodegenerative conditions, and such device will also be used in combination with its microbubbles.
MK-6240
MK-6240 is an investigational late-stage F-18-labeled PET imaging agent designed to detect tau protein in the form of neurofibrillary tangles in the brains of patients with known or suspected Alzheimer’s disease. MK-6240 is in Phase 3 development and is also being used as a biomarker in more than 100 ongoing academic and industry-sponsored clinical trials, many for late-stage therapeutic candidates. Research revenue is derived from the use of MK-6240 in those clinical trials and includes milestone and dose-related payments.
NAV-4694
NAV-4694 is an investigational late-stage F-18-labeled PET imaging agent that targets beta amyloid in Alzheimer’s disease. NAV-4694 is in Phase 3 development and is also being used in academic and industry-sponsored clinical trials. Research revenue is derived from the use of NAV-4694 in those clinical trials and includes milestone and dose-related payments.
RELISTOR
On August 2, 2023, the company sold its right to its RELISTOR net sales royalty asset under its license agreement with Bausch; the company retained the rights to future sales-based milestone payments.
aBSI
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. on August 5, 2019. In February 2020, Progenics received a CE mark for the standalone workstation model of aBSI, meeting the quality standards set by the European Economic Area. In September 2020, the FDA granted 510(k) clearance for the use of aBSI as software-as-a-medical device on a GE Healthcare imaging system.
PYLARIFY AI
PYLARIFY AI is an FDA-cleared AI 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. The company’s subsidiary, EXINI, was granted 510(k) clearance by the FDA in the U.S. and received a CE mark in Europe for aPROMISE. The company commercially launched aPROMISE under the name PYLARIFY AI in the U.S. in November 2021, and the FDA granted the company an additional 510(k) clearance during the second quarter of 2022.
Flurpiridaz
In 2017, the company entered into a definitive, exclusive global Collaboration and License Agreement with GE Healthcare for development and worldwide commercialization of flurpiridaz, an F-18-based PET MPI agent designed to assess blood flow to the heart in patients suspected of CAD. Under the agreement, the company received an upfront cash payment of $5.0 million and is eligible to receive up to $60.0 million in regulatory and sales milestone payments, tiered double-digit royalties on the U.S. sales, and mid-single digit royalties on sales outside of the U.S. In September 2024, GE Healthcare announced that it had received FDA approval of flurpiridaz under the name Flyrcado for coronary artery disease diagnosis and anticipated commercialization to begin in the first half of 2025.
Clinical Development Candidates
In addition to the company’s commercial products and strategic partnerships with third parties, the company also has ongoing clinical development programs, including the following:
MK-6240 is an investigational late-stage F-18-labeled PET imaging agent that targets tau tangles in Alzheimer’s disease. MK-6240 is in Phase 3 development and is also being used in over 100 ongoing academic and industry trials, many for late-stage therapeutic candidates.
NAV-4694 is an investigational late-stage F-18-labeled PET imaging agent that targets beta amyloid in Alzheimer’s disease, NAV-4694 is in Phase 3 development and is also being used in academic and industry-sponsored clinical trials.
PNT2002 is an investigational PSMA-targeted radiopharmaceutical therapy for the treatment of mCRPC. On December 18, 2023, the company announced positive topline results from SPLASH, the Phase 3 registrational trial for PNT2002 designed to evaluate superiority to the standard of care in mCRPC pre-chemotherapy patients who have failed one androgen receptor pathway inhibitor. At the time of the analysis, interim OS results were immature (46% of protocol pre-specified target OS events reached), and the HR was 1.11. On September 15, 2024, the company presented additional clinical data from initial topline results of SPLASH during the European Society of Medical Oncology Congress 2024. On November 6, 2024, the company announced that the second interim analysis performed at 75% of protocol pre-specified OS demonstrated results for both rPFS and OS that did not materially change from the interim analysis that was performed at 46% of pre-specified OS events. Crossover adjusted analyses were post hoc, and the company is continuing to review the data and perform additional subset analyses in collaboration with its partner in preparation for further interactions on its path forward.
PNT2003 is an investigational SSTR therapy with non-carrier added lutetium-177, which is in registration to treat patients with SSTR-positive neuroendocrine tumors. On January 11, 2024, the company announced that its ANDA for PNT2003, which included Paragraph IV certification, was accepted for filing by the FDA. Pursuant to the procedure set forth in the Hatch Waxman Act, the company was sued for patent infringement by Advanced Accelerator Applications USA, Inc. and Advanced Accelerator Applications SA, each a Novartis entity.
LNTH-1363S is an investigational fibroblast activation protein, alpha targeted, copper-64 labeled PET imaging agent candidate that could have broad potential imaging applicability and use in oncology. The company completed a Phase 1 study for LNTH-1363S to evaluate the pharmacokinetics, biodistribution, and radiation dosimetry in adult healthy volunteers and initiated a Phase 1/2a study.
LNTH-2401, also known as 68Ga-DOTA-RM2, is a novel radiodiagnostic targeting the gastrin-releasing peptide receptor.
LNTH-2402, also known as 177Lu-DOTA-RM2, is a novel gastrin-releasing peptide receptor targeted radiotherapeutic for solid tumors, including prostate, breast, lung, and other cancers. The company intends to begin a Phase 1/2a study with LNTH-2402 in prostate cancer patients in 2025.
LNTH-2403, also known as LRRC15, is a leucine-Rich Repeat-Containing Protein 15 targeted radiotherapeutic. It received Orphan Drug and Rare Pediatric Disease designation from the FDA for the treatment of osteosarcoma.
LNTH-2404 is a Trophoblast cell surface antigen-2 targeted radiotherapeutic designed to target TROP2, an intracellular calcium signal transducer that is overexpressed in various types of adenocarcinomas with minimal expression in normal tissues and is associated with tumor aggressiveness, poor prognosis, and drug resistance.
Research and Development
For the year ended December 31, 2024, the company invested $168.1 million in research and development (‘R&D’) primarily related to its clinical development candidates.
Distribution, Marketing and Sales
With respect to the company’s medical devices:
Progenics received a CE mark for the standalone workstation model of aBSI, meeting the quality standards set by the European Economic Area. In September 2020, the FDA granted 510(k) clearance for the use of aBSI as software-as-a-medical device on a GE Healthcare imaging system.
EXINI was granted 510(k) clearance by the FDA in the U.S. and received a CE mark in Europe for aPROMISE. The company launched aPROMISE under the name PYLARIFY AI in the U.S.
PYLARIFY sales are generated in the U.S. through an internal PYLARIFY sales team, as well as a sales team at some of the company’s PMF partners. Sales of DEFINITY are generated in the U.S. through an internal DEFINITY sales team. While a small portion of the company’s SPECT product sales in the U.S. are generated through its internal sales force to hospitals and clinics that maintain their own in-house radiopharmaceutical preparation capabilities, the company primarily sells its SPECT products, including TechneLite, NEUROLITE, Xenon, and CARDIOLITE, to large radiopharmacy chains. The company has licensed RELISTOR to Bausch, and while the company has sold the right to its RELISTOR net sales royalties under its license agreement, it has retained the rights to future sales-based milestone payments generated by Bausch.
Flurpiridaz F-18 is licensed to GE Healthcare, which is commercializing it as Flyrcado in the United States. The company is entitled to milestone and royalty-based payments for Flyrcado.
Competition
For PYLARIFY, the company’s principal competitors are Telix Pharmaceuticals Limited, Novartis AG, and Blue Earth Diagnostics Ltd., a subsidiary of Bracco Diagnostics Inc. (‘Bracco’).
For DEFINITY, the company’s competitors include GE Healthcare and Bracco.
For a number of the company’s SPECT products, its competitors include Curium, GE Healthcare, Bracco, and Jubilant Life Sciences, an affiliate of JHS and Jubilant Radiopharma, and potentially BWXT Medical.
Supply Relationships
For the year ended December 31, 2024, the company’s largest suppliers of raw materials and supplies were Institute for Radioelements (‘IRE’), the Australian Nuclear Science and Technology Organisation (‘ANSTO’), and NTP Radioisotopes (‘NTP’), which, in the aggregate, accounted for approximately 7.8% of its total purchases and relate specifically to TechneLite.
Manufacturing and Supply Arrangements
The company has the following technology transfer and manufacturing and supply agreements in place for some of its major products:
PYLARIFY—The company has entered into commercial supply agreements with different PMF networks. The company’s agreements with its PMF networks allow for termination upon the occurrence of specified events, including material breach or bankruptcy by either party, and have various termination dates generally terminating between 2027 and 2030 and subject to renewal provisions.
DEFINITY, CARDIOLITE, and NEUROLITE—In February 2022, the company entered into a Manufacturing and Supply Agreement with JHS, for the manufacture of DEFINITY, CARDIOLITE, NEUROLITE, and evacuation vials, the latter being an ancillary component for its TechneLite generators. The agreement expires on December 31, 2027, and can be renewed upon mutual consent.
Intellectual Property
Trademarks, Service Marks, and Trade Names
The company owns various trademarks, service marks, and trade names, including among others, PYLARIFY, DEFINITY, and Find Fight and Follow. The company has generally registered these trademarks, as well as others, in the U.S. and/or numerous foreign jurisdictions.
Intellectual Property Protection on Selected Assets
PYLARIFY — A portfolio of patents protects PYLARIFY, both in the U.S. and internationally, and the company continues to pursue additional patent protection. There are six Orange Book-listed patents for PYLARIFY. The company’s longest duration Orange Book-listed PYLARIFY patent extends until June 2037. The NCE-1 date for PYLARIFY is May 26, 2025. This is the date after which the FDA is allowed to accept an ANDA or 505(b)(2) applications from generic challengers.
DEFINITY — A portfolio of patents protects the use and manufacturing of DEFINITY and also the VIALMIX RFID device, both in the U.S. and internationally. There are nine Orange Book-listed patents for DEFINITY. The company’s longest duration Orange Book-listed DEFINITY patent extends until May 2037.
TechneLite — The company owns patents in the U.S. and various foreign countries on certain component technology expiring in 2029, and the company is pursuing additional patent protection in the U.S. and worldwide on other component technology that, if granted, would expire in 2040. In addition, given the significant know-how and trade secrets associated with the methods of manufacturing and assembling the TechneLite generator, the company has a substantial amount of valuable and defensible proprietary intellectual property associated with the product.
aPROMISE — The U.S. patents and pending patent applications worldwide relating to automated medical image analysis have expiration dates ranging from 2037 to 2041.
Other Nuclear Products — Neither CARDIOLITE nor NEUROLITE is covered any longer by patent protection. The company has patent protection for an improved container for Xenon in the U.S., Canada, and Australia that expires in October 2035.
aBSI — The company owns patents relating to automated detection of bone cancer metastases. The patents on this technology expire in the U.S. in 2032 and outside of the U.S. in 2028. Further, the company owns a U.S. patent and has patent applications that are pending in the U.S. and worldwide relating to aBSI improvements, which have expiration ranging from 2040 to 2041.
flurpiridaz (Flyrcado) — The company owns 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.
PNT2002 — The company exclusively licenses 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 PNT2002. The granted U.S. patents expire in 2041.
PNT2003 — The company exclusively licenses 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 PNT2003 which, if granted, would expire in 2043.
MK-6240 — The company exclusively licenses patents directed to composition of matter and methods of use of MK-6240 which expire in 2035.
NAV-4694 — The company exclusively licenses patents directed to composition of matter and methods of use of NAV-4694 which expire in 2029.
LNTH-1363S — The company exclusively licenses patent applications directed to compositions of matter and methods of use of LNTH-1363S. If granted, the last patent will expire in 2043.
Regulatory Matters
The company is required to register for permits and/or licenses with, seek approvals from, and comply with operating and security standards of, the FDA, the U.S. Nuclear Regulatory Commission (‘NRC’), the U.S. Department of Health and Human Services, Health Canada, the European Medicines Agency, the U.K. Medicines and Healthcare Products Regulatory Agency, the NMPA, and various state and provincial boards of pharmacy, state and provincial controlled substance agencies, state and provincial health departments and/or comparable state and provincial agencies, as well as foreign agencies, and certain accrediting bodies depending upon the type of operations and location of product distribution, manufacturing, and sale.
Any drug products for which the company receives 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.
The FDA also regulates the preclinical and clinical testing, design, manufacture, safety, efficacy, labeling, storage, record keeping, sales and distribution, post-market adverse event reporting, import/export, and advertising and promotion of any medical devices that the company distributes pursuant to the FDCA and FDA’s implementing regulations.
Because the company’s operations include the manufacture and distribution of medical radioisotopes and other medical products, it is subject to regulation by the NRC and the departments of health of each state in which it operates and the applicable state boards of pharmacy.
The company is neither a ‘covered entity’ nor a ‘business associate’ subject directly to regulation under HIPAA; HIPAA’s criminal provisions can apply to entities other than ‘covered entities’ or ‘business associates’ in certain circumstances.
The company is subject to various federal and foreign laws that govern its international business practices with respect to payments to government officials. Those laws include the Foreign Corrupt Practices Act (‘FCPA’), which prohibits U.S. companies and their representatives from paying, offering to pay, promising, or authorizing the payment of anything of value to any foreign government official, government staff member, political party, or political candidate for the purpose of obtaining or retaining business or to otherwise obtain favorable treatment or influence a person working in an official capacity.
Those laws also include the U.K. Bribery Act (‘Bribery Act’), which proscribes giving and receiving bribes in the public and private sectors, bribing a foreign public official, and failing to have adequate procedures to prevent employees and other agents from giving bribes.
History
Lantheus Holdings, Inc. was founded in 1956. The company was incorporated in 1999.
