What changed in this filing

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Item 1A. Risk Factors

2022-02-24 compared with 2021-02-25 · 321 added, 311 removed, 544 unchanged (54% of the section changed)

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• Our ability to continue to grow the appropriate use of DEFINITY in suboptimal echocardiograms in the face of segment competition from other echocardiography ultrasound enhancing agents and potential generic competition as a result of patent and regulatory exclusivity expirations.

• The instability of the global Mo-99 supply, including periodic supply outages and limitations at the NTP Radioisotopes (“NTP”) processing facility in South Africa and the Australian Nuclear Science and Technology Organisation’s (“ANSTO”) processing facility in Australia, in each case resulting in our inability to fill some or all of the demand for our TechneLite generators on certain manufacturing days during the outage or limitation periods.

• Our dependence upon third parties for the manufacture and supply of a substantial portion of our products, raw materials and components, including DEFINITY at JHS and DEFINITY RT at SBL.

• Our ability to successfully launch PYLARIFY as a commercial product, including (A) our ability to obtain FDA approval for additional PMFs that could manufacture PYLARIFY, (B) the ability of those PMFs to supply PYLARIFY to customers, (C) our ability to sell PYLARIFY to customers, and (D) our ability to obtain and maintain adequate coding, coverage and payment for PYLARIFY.

• Our ability to successfully launch PYLARIFY AI as a commercial product.

• Risks related to RELISTOR, commercialized by Bausch, and that the revenues generated for us thereby may not meet expectations.

• Risks related to the commercialization of AZEDRA, including in connection with market acceptance and reimbursement, that may cause the product not to meet revenue or operating income expectations.

• Risks associated with our DEFINITY RT formulation, approved by the FDA in November 2020, including our ability gain post-approval market acceptance and adequate reimbursement.

Risks Related to Our Portfolio of Clinical Development Candidates

• Risks associated with our lead agent in development, PyL, for which an New Drug Application (“NDA”) was accepted by the FDA and granted priority review with an assigned Prescription Drug User Fee Act (“PDUFA”) action date of May 28, 2021, including:

• Our ability to obtain FDA approval of PyL in 2021;

• Our ability to successfully gain post-approval market acceptance and adequate reimbursement for PyL;

• Our dependence upon third parties for the manufacture and supply of PyL and the timing of that manufacturing capacity becoming available;

• Our ability to compete successfully with other prostate cancer imaging agents, including those that target prostate specific membrane antigen (“PSMA”).

• Risks associated with flurpiridaz F 18, which in 2017 we out-licensed to GE Healthcare, including:

• GE Healthcare’s ability to successfully complete the Phase 3 development program, including delays in enrollment that have resulted from the COVID-19 pandemic;

• GE Healthcare’s ability to obtain FDA approval;

• GE Healthcare’s ability to gain post-approval market acceptance and adequate reimbursement.

• Risks related to the development and commercialization of our AI product offerings, including relating to assessment of disease burden targeting PSMA;

• Risks associated with 1095, including delays in enrollment that have resulted from the COVID-19 pandemic and our ability to successfully complete the Phase 2 study in mCRPC.

Risks related to the Integration of the Progenics Acquisition

• The continued integration of the Progenics Acquisition may involve unexpected costs, liabilities or delays, including the ability of our combined business to continue to retain and hire key personnel and maintain relationships with customers, suppliers and others with whom we or Progenics do business.

• The anticipated benefits of the Progenics Acquisition may not be fully realized or may take longer to realize than we expect.

• The contractual contingent value rights (“CVRs”) we issued as part of the Progenics Acquisition may result in substantial future payments and could divert the attention of our management.

• Risks associated with our DEFINITY RT formulation, approved by the FDA in November 2020, including our ability to gain post-approval market acceptance and adequate coding, coverage and payment.

Risks Related to Reimbursement and Regulation

• The dependence of certain of our customers upon third-party healthcare payors and the uncertainty of third-party coverage and reimbursement rates.

• The dependence of many of our customers upon third party healthcare payors and the uncertainty of third party coverage and reimbursement rates.

• Uncertainties regarding the impact of U.S.

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Risks Related to our Business Operations and Financial Results

• The impact of the on-going global COVID-19 pandemic on our business, financial condition or prospects, including:

a decline in the volume of procedures and treatments using our products, in particular Xenon because of institutional concerns and professional society guidelines relating to the possible spread of COVID-19 to technicians and other patients given that Xenon is both inhaled and exhaled by the patient;

potential delays and disruptions to global supply chains, manufacturing activities, logistics, operations, clinical development programs, employees and contractors, the business activities of our suppliers, distributors, customers and other business partners;

• The impact of the ongoing global COVID-19 pandemic on our business, financial condition or prospects, including:

a decline in the volume of procedures and treatments using our products;

potential delays and disruptions to global supply chains, manufacturing activities, logistics, operations, and clinical development programs;

the business activities of our suppliers, distributors, customers and other business partners;

the difficulty in recruiting and retaining employees and contractors;

and the effects on worldwide economies, financial markets, social institutions, labor markets and healthcare systems.

• Our ability to hire or retain the number of qualified personnel, particularly scientific, medical and sales personnel, required for our business.

• Our ability to introduce new products and adapt to an evolving technology and medical practice landscape.

• Risks associated with our investment in, and construction of, additional specialized manufacturing capabilities at our North Billerica, Massachusetts facility, including our ability to bring the new capabilities online in 2021.

• Risks associated with our investment in and operation of our specialized manufacturing facility at our North Billerica, Massachusetts campus.

Risks Related to Our Portfolio of Clinical Development Candidates

• Risks associated with flurpiridaz F 18, which we out-licensed to GE Healthcare in 2017, including GE Healthcare’s ability to (A) successfully complete the Phase 3 development program, including delays in enrollment that have resulted from the COVID-19 pandemic, (B) obtain FDA approval, and (C) gain post-approval market acceptance and adequate coding, coverage and payment.

• Risks associated with 1095, including delays in enrollment that have resulted from the COVID-19 pandemic and our ability to successfully complete the Phase 2 study in mCRPC.

• Risks associated with our clinical development candidate LMI 1195

Risks Related to our Capital Structure

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• Risks related to the ownership of our common stock.

• The contractual contingent value rights (“CVRs”) we issued as part of the Progenics Acquisition may result in substantial future payments to holders of the CVRs.

Risks Related to Our Portfolio of Commercial Products

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The growth of our business is substantially dependent on our ability to continue to grow the appropriate use of DEFINITY in suboptimal echocardiograms.

There were approximately 31.5 million echocardiograms in 2020 according to a third-party source.

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

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

market for ultrasound enhancing agents in echocardiography procedures as of December 31, 2020.

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

DEFINITY currently competes with Optison, a GE Healthcare product, Lumason, a Bracco product, as well as echocardiography without ultrasound enhancing agents and other non-echocardiography agents.

We launched DEFINITY in 2001, and we continue to actively pursue additional patents in connection with DEFINITY and DEFINITY RT, both in the U.S.

and internationally.

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

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

Outside of the U.S., while our original DEFINITY

patent protection and regulatory exclusivity have generally expired, we are currently prosecuting additional DEFINITY and DEFINITY RT patents to obtain similar patent protection as in the U.S.

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 2021, 2023 and 2037.

for DEFINITY RT, which became commercially available in the fourth quarter of 2021, we have five Orange Book-listed patents, including a composition of matter patent which expires in 2035.

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

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

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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 ANDAs for generic versions of drugs before the expiration of an Orange Book-listed patent covering the innovator product if the ANDA applicant demonstrates, among other things, that (i) its generic candidate is the same as the innovator product by establishing bioequivalence and providing relevant chemistry, manufacturing and product data, and (ii) the marketing of that generic candidate does not infringe an Orange Book-listed patent or that an Orange Book-listed patent is invalid.

The ANDA applicant must also give Notice to the innovator, which would then enable the innovator to challenge the ANDA applicant in court within 45 days of receiving such Notice.

If the innovator challenges the ANDA applicant in court in a timely manner, then FDA approval to commercialize the generic candidate will be stayed (that is, delayed) for up to 30 months while the dispute between the innovator and the ANDA applicant is resolved in court.

The 30 month stay can be shortened if the patent infringement suit is resolved in the ANDA applicant’s favor before the 30 month stay expires, and this may involve a successful challenge of the patent’s validity in U.S.

Patent and Trademark Office, or USPTO, proceedings and appeals process.

As of the date of filing of this Annual Report on Form 10-K, we have not received any such Notice from any ANDA applicant but can give no assurance that we will not receive a Notice in the future.

If we were to receive any such Notice in the future, we would review the Notice, evaluate the strength of any potential patent infringement claims, and be prepared to challenge the ANDA applicant in a timely fashion, which would thereby trigger the stay of up to 30 months.

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 a generic candidate infringes our Orange Book-listed patent, or that we would be successful defending the validity of our Orange Book-listed patent in court or in a USPTO adversarial proceeding.

As part of our microbubble franchise strategy, (i) we have developed and received FDA approval for DEFINITY RT, a modified formulation of DEFINITY, (ii) we look for other opportunities to expand our microbubble franchise, including new applications beyond echocardiography and ultrasound enhancing agent imaging generally such as our strategic arrangements with Cerevast, CarThera and Insightec, and (iii) we have completed construction of our specialized in-house manufacturing capabilities at our North Billerica facility for DEFINITY and, potentially, other sterile vial products.

However, we can give no assurance that our microbubble franchise strategy will be successful or that a modified formulation, new applications or new manufacturing capabilities will grow our microbubble franchise.

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

among other things, that (i) its generic candidate is the same as the innovator product by establishing bioequivalence and providing relevant chemistry, manufacturing and product data, and (ii) either the marketing of that generic candidate does not infringe the Orange Book-listed patent(s) or the Orange Book-listed patent(s) is invalid.

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

The ANDA applicant or the Section 505(b)(2) applicant (if relying on studies related to the innovator product) (together, the “Applicant”) must also give Notice to the innovator, which would then enable the innovator to file suit against the Applicant within 45 days of receiving the Notice.

If the innovator challenges the Applicant in court in a timely manner, then FDA approval to commercialize the generic candidate will be stayed (that is, delayed) for up to 30 months while the dispute between the innovator and the Applicant is resolved in court.

The 30 month stay can be shortened if the patent infringement suit is resolved in the Applicant’s favor before the 30 month stay expires, and this may involve a successful challenge of the patent’s validity in U.S.

Patent and Trademark Office (“USPTO”) proceedings and appeals process.

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.

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 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 such Notice from any Applicant, but we can give no assurance that we will not receive a Notice in the future.

If we were to receive any such Notice in the future, we would review the Notice, evaluate the strength of any potential patent infringement claims, and be prepared to challenge the Applicant in a timely fashion, which would thereby trigger the stay of up to 30 months.

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 of our Orange Book-listed patent in court or in a USPTO adversarial proceeding.

In addition, as discussed in our risk factor “Our business and industry are subject to complex and costly regulations.

If government regulations are interpreted or enforced in a manner adverse to us or our business, we may be subject to enforcement actions, penalties, exclusion and other material limitations on our operations.” set forth below, if the FDA reclassified one or more of our imaging agents, such as DEFINITY, as a “device” rather than a “drug”, we do not know when such reclassification would become effective, how any transition rules would be formulated or applied, and whether or not the legal framework provided by the Hatch-Waxman Act would be preserved for some time after such reclassification.

As part of our microbubble franchise strategy, (i) we have developed and received FDA approval for DEFINITY RT, a modified formulation of DEFINITY, (ii) we look for other opportunities to expand our microbubble franchise, including new applications beyond echocardiography and ultrasound enhancing agent imaging generally such as our strategic arrangements with Cerevast, CarThera, Insightec and AHN, and (iii) 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 sNDA, authorizing commerical manufacturing of DEFINITY at our new facility.

However, we can give no assurance that our microbubble franchise strategy will be successful or that the modified formulation, new applications or new manufacturing capabilities will grow our microbubble franchise.

If we are not able to continue to (i) grow DEFINITY and DEFINITY RT sales, which depend on one or more of the growth of echocardiograms, the growth in the appropriate use of ultrasound enhancing agents in suboptimal echocardiograms, and our ability to sustain and grow our leading position in the U.S.

echocardiography ultrasound enhancing agent market, or (ii) be successful with our microbubble franchise strategy, we may not be able to continue to grow the revenue and cash flow of our business, which could have a negative effect on our business, results of operations and financial condition.

Our dependence upon third parties for the manufacture and supply of a substantial portion of our products and certain key components and raw materials could prevent us from delivering our products to our customers in the required quantities, within the required timeframes, or at all, which could result in order cancellations and decreased revenues.

We obtain a substantial portion of our products from third party manufacturers and suppliers.

We rely on JHS as a substantial supplier of DEFINITY, as well as our sole source manufacturer of NEUROLITE, Cardiolite and evacuation vials.

We rely on SBL as our sole source manufacturer of DEFINITY RT.

We rely on various other sole source suppliers for some of our key components and raw materials.

Based on our current estimates, we believe that we will have sufficient supply of DEFINITY, NEUROLITE, Cardiolite and evacuation vials from JHS (together with DEFINITY from our in-house manufacturing facility), and sufficient supply of saline from our sole manufacturer, to meet expected demand.

However, we can give no assurances that JHS or our other manufacturing partner will be able to manufacture and distribute our products in a high quality and timely manner and in sufficient quantities to allow us to avoid product stock-outs and shortfalls.

PYLARIFY is manufactured by a nationwide network of PMFs with radioisotope-producing cyclotrons.

The radioisotope in PYLARIFY is fluorine-18, which has a 110-minute half-life, so PYLARIFY is manufactured and distributed rapidly to end-users.

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

Although we have qualified and 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 or that the PMFs will not experience issues with their ability to manufacture and deliver PYLARIFY to our customers.

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

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

We receive bulk unprocessed Xenon from IRE resulting from highly-enriched uranium (“HEU”) Mo-99 production, which we process and finish for our customers.

We do not yet receive Xenon resulting from low-enriched uranium (“LEU”) Mo-99 production at IRE and can give no assurances as to the timing of the availability of LEU Xenon.

We believe we will have a sufficient supply of Xenon to meet our customers’ needs.

However, until IRE converts to LEU Xenon production or we can qualify an additional source of bulk unprocessed Xenon, we will rely on IRE as a sole source provider of HEU Xenon.

1095 is currently manufactured only at the CPDC in Ontario, Canada.

Until December 2019, the CPDC was subject to an Import Alert by the FDA, which restricted the CPDC’s ability to ship products to the U.S.

Although the CPDC has since been cleared by the FDA to ship products to the U.S., there can be no guarantee that the CPDC, or any other ex-U.S.

third party manufacturer that we may partner with in the future, will not be subject to similar restrictions in the future.

In addition to the products described above, for reasons of quality assurance or cost-effectiveness, we purchase certain components and raw materials from sole suppliers (including, for example, the lipid blend material and perflutren gas used in the manufacturing of DEFINITY, the specially designed chemistry synthesis boxes and consumables used in the manufacturing of PYLARIFY and the lead casing for our TechneLite generators).

Because we do not control the actual production of many of the products we sell and many of the raw materials and components that make up the products we sell, we may be subject to delays caused by interruption in production based on events and conditions outside of our control.

If we or one of our manufacturing partners or suppliers experiences an event, including a supply chain disruption, shortage or delay, logistics issue, labor dispute, natural disaster, fire, power outage, machinery breakdown, security problem, failure to meet regulatory requirements, product quality issue, technology transfer issue, cybersecurity breach or other issue, we or one of our manufacturing partners or suppliers may be unable to manufacture the relevant products at previous levels or on the forecasted schedule, if at all.

Due to the stringent regulations and requirements of the governing regulatory authorities regarding the manufacture of our products, we may not be able to quickly restart manufacturing at a third party or our own facility or establish additional or replacement sources for certain products, components or materials.

In addition to our existing manufacturing relationships, we are also pursuing new manufacturing relationships to establish and secure additional or alternative suppliers for our commercial products.

We have also constructed a specialized in-house manufacturing facility at our North Billerica, Massachusetts 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.

This project should deliver supply chain redundancy for our current portfolio and the opportunity for margin expansion.

However, we cannot assure you that these activities or any of our additional supply activities will be successful or that we will be able to avoid or mitigate interim supply shortages before new sources of product are fully functional and qualified.

In addition, we cannot assure you that our existing manufacturers or suppliers or any new manufacturers or suppliers can adequately maintain either their financial health, technical capabilities or regulatory compliance to allow continued production and supply.

A reduction or interruption in manufacturing, or an inability to secure alternative sources of raw materials or components, could eventually have a material adverse effect on our business, results of operations, financial condition and cash flows.

The global supply of Mo-99 is fragile and not stable.

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These processing sites provide us Mo-99 from five of the six main Mo-99-producing reactors in the world, namely BR2 in Belgium, LVR-15 in the Czech Republic, HFR in The Netherlands, SAFARI in South Africa and OPAL in Australia.

Our agreement with NTP, acting for itself and on behalf of its subcontractor ANSTO, expires on March 31, 2022.

We are actively negotiating a new supply agreement with NTP, although we can give no assurance that we will be able to reach an agreement on mutually acceptable terms or at all.

In the event we are not able to enter into an agreement on mutually acceptable terms or at all,

we would expect to attempt to increase our purchases of Mo-99 from IRE and enter into a direct arrangement with ANSTO, but we can give no assurance that we would be able to increase our purchases from IRE or directly purchase from ANSTO or that there would be no disruption in our ability to fill some or all of the demand for our TechneLite generators on certain manufacturing days.

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

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

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

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

Under the terms of the supply agreement, 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 2022.

However, we cannot assure you that SHINE or any other possible additional sources of Mo-99 will result in commercial quantities of Mo-99 for our business, or that these new suppliers together with our current suppliers will be able to deliver a sufficient quantity of Mo-99 to meet our needs.

To augment our current supply of Mo-99, we entered into a strategic arrangement with 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 2023.

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.

U.S., Canadian and international governments have encouraged the development of a number of alternative Mo-99 production projects with existing reactors and technologies as well as new technologies.

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Absent a new supplier, a supply disruption relating to uranium targets or fuel could have a substantial negative effect on our business, results of operations, financial condition and cash flows.

The instability of the global supply of Mo-99, including supply shortages, has resulted in increases in the cost of Mo-99, which has negatively affected our margins, and more restrictive agreements with suppliers, which could further increase our costs.

With the general instability in the global supply of Mo-99, we have faced substantial increases in the cost of Mo-99 in comparison to historical costs.

We expect these cost increases to continue in the future as the Mo-99 suppliers move closer to a full cost recovery business model.

The Organization of Economic Cooperation and Development (“OECD”) defines full cost recovery as the identification of all of the costs of production and recovering these costs from the market.

While we are generally able to pass Mo-99 cost increases on to our customers in our customer contracts, if we are not able to do so in the future, our margins may decline further with respect to our TechneLite generators, which could have a material adverse effect on our business, results of operations, financial condition and cash flows.

Our dependence upon third parties for the manufacture and supply of a substantial portion of our products could prevent us from delivering our products to our customers in the required quantities, within the required timeframes, or at all, which could result in order cancellations and decreased revenues.

We obtain a substantial portion of our products from third party manufacturers and suppliers.

We rely on JHS as our sole source manufacturer of DEFINITY, NEUROLITE, Cardiolite and evacuation vials.

We rely on SBL as our sole source manufacturer of DEFINITY RT.

Based on our current estimates, we believe that we will have sufficient supply of DEFINITY, NEUROLITE, Cardiolite and evacuation vials from JHS, and sufficient supply of saline from our sole manufacturer, to meet expected demand.

Currently, regulatory authorities in certain countries have not yet approved JHS as a manufacturer of certain of our products.

Accordingly, until those regulatory approvals have been obtained, our business, results of operations, financial condition and cash flows will continue to be adversely affected.

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

We receive bulk unprocessed Xenon from IRE resulting from HEU Mo-99 production, which we process and finish for our customers.

We do not yet receive Xenon resulting from LEU Mo-99 production at IRE and can give no assurances as to the timing of the availability of LEU Xenon.

We believe we will have a sufficient supply of Xenon to meet our customers’ needs.

However, until IRE converts to LEU Xenon production or we can qualify an additional source of bulk unprocessed Xenon, we will rely on IRE as a sole source provider of HEU Xenon.

1095 is currently manufactured only at the CPDC.

Until December 2019, the CPDC was subject to an Import Alert by the FDA, which restricted the CPDC’s ability to ship products to the U.S.

Although the CPDC has since been cleared by the FDA to ship products to the U.S., there can be no guarantee that the CPDC, or any other third-party manufacturer that we may partner with in the future, will not be subject to similar restrictions in the future.

In addition to the products described above, for reasons of quality assurance or cost-effectiveness, we purchase certain components and raw materials from sole suppliers (including, for example, the lead casing for our TechneLite generators and the lipid blend material used in the processing of DEFINITY).

At our North Billerica, Massachusetts facility, we manufacture TechneLite on a highly automated production line, as well as Thallium and Gallium using our older cyclotron technology and Xenon and QUADRAMET using our hot cell infrastructure.

As with all manufacturing facilities, equipment and infrastructure age and become subject to increasing maintenance and repair.

If we or one of our manufacturing partners experiences an event, including a labor dispute, natural disaster, fire, power outage, machinery breakdown, security problem, failure to meet regulatory requirements, product quality issue, technology transfer issue or other issue, we may be unable to manufacture the relevant products at previous levels or on the forecasted schedule, if at all.

In addition to our existing manufacturing relationships, we are also pursuing new manufacturing relationships to establish and secure additional or alternative suppliers for our commercial products.

We have also completed construction of our specialized in-house manufacturing capabilities at our North Billerica, Massachusetts facility.

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

Our ability to successfully launch PYLARIFY as a commercial product is dependent on (A) our ability to obtain FDA approval for additional PMFs that could manufacture PYLARIFY, (B) the ability of those PMFs to supply PYLARIFY to customers, (C) our ability to sell PYLARIFY to customers, and (D) our ability to obtain and maintain adequate coding, coverage and payment for PYLARIFY.

The commercial launch of PYLARIFY is complex and expensive.

To manufacture PYLARIFY, we assembled and qualified 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.

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

Although we successfully qualified 21 PMFs in 2021 and continue to qualify additional PMFs in 2022, such that PYLARIFY is broadly available across the U.S.

(including through our efforts to fly doses to certain markets ahead of PMF activation), 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.

PYLARIFY is sold in the U.S.

to hospitals, independent imaging centers and government facilities and are generated through a PYLARIFY direct sales team and a sales team at some of our PMF partners.

We generally do not use group purchasing arrangements to sell PYLARIFY and require contracts to be entered into directly with each customer.

During 2021, we hired additional employees to assist us with this commercialization of PYLARIFY.

Our ability to continue to successfully launch PYLARIFY depends, in part, on our ability to continue to enter into arrangements directly with the hospitals, independent imaging centers and government facilities that we serve.

Any delay or inability to enter into these arrangements could have an adverse impact on our future business, results of operations, financial condition and cash flows.

In addition, obtaining adequate coding, coverage and payment for PYLARIFY is critical, 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 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 for PYLARIFY, enabling traditional Medicare to provide an incremental payment for PET/CT scans performed with PYLARIFY in the hospital outpatient setting.

If other government payors or private payors do not provide adequate

reimbursement for the use of PYLARIFY, our future business, results of operations, financial condition and cash flows could be adversely affected.

The successful launch of PYLARIFY is also dependent on our ability to establish PYLARIFY as a leading PET diagnostic for men with prostate cancer in the approved indications.

PYLARIFY currently competes with Telix Pharmaceuticals Limited’s recently-approved Illuccix (gallium-68 PSMA-11 injection) and Bracco’s Axumin (fluciclovine F 18).

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.

To the extent we are unsuccessful in establishing the use of PYLARIFY for approved indications or we lose market share to existing or future competitors, such lack of success or loss of market share could have an adverse impact on our future business, results of operations, financial condition and cash flows.

In addition, 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.

We may not be able to successfully launch PYLARIFY AI as a commercial product.

We announced in November 2021 that PYLARIFY AI, our FDA-cleared medical device software, was commercially available in the United States.

Our ability to successfully launch PYLARIFY AI as a commercial product depends in part on, among other things:

• the market receptivity to PYLARIFY AI as a new digital application for quantitative assessment of PSMA PET/CT images in prostate cancer;

• our ability, and our distributors’ abilities, to secure customers’ internal approvals and sell and deploy PYLARIFY AI at customer locations;

• interruptions or performance problems associated with our digital application, including a service outage;

• a network or data security incident that allows unauthorized access to our network or data or our customers’ data.

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

We rely on Bausch to develop and commercialize RELISTOR, exposing us to significant risks.

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Bausch’s ability to optimally commercialize either oral or subcutaneous RELISTOR in a given jurisdiction may be impacted by applicable labeling and other regulatory requirements.

If clinical trials indicate, or regulatory bodies are concerned about, actual or

possible serious problems with the safety or efficacy of RELISTOR, Bausch may stop or significantly slow further development or commercialization of RELISTOR.

If clinical trials indicate, or regulatory bodies are concerned about, actual or possible serious problems with the safety or efficacy of RELISTOR, Bausch may stop or significantly slow further development or commercialization of RELISTOR.

In such an event, we could be faced with either further developing and commercializing the drug on our own or with one or more substitute collaborators, either of which paths would subject us to the development, commercialization, collaboration and/or financing risks.

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Since then, the AZEDRA commercial program has faced numerous challenges, including, among other things:

• limited success in manufacturing patient-ready doses of AZEDRA;

• decisions by treating physicians and patients to defer treatment and by hospital facilities to limit access for our representatives until COVID-19 infection rates subside;

• challenges in securing I-131 supply and manufacturing patient-ready doses of AZEDRA;

• a small Orphan Drug patient population;

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Under the fiscal year 2022 IPPS Final Rule, published in September 2021, CMS finalized continuation of AZEDRA’s NTAP for fiscal year 2022—i.e., from October 1, 2021 through September 30, 2022.

Although there is potential for AZEDRA to receive an additional year of NTAP coverage, CMS may not decide to renew NTAP coverage for the period of October 1, 2021 through September 30, 2022.

AZEDRA’s NTAP will most likely expire September 30, 2022.

If post-pass-through payment levels impact market acceptance for AZEDRA, the drug may not generate enough revenue to make it economically viable.

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

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

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.

We may not be able to maintain Orphan Drug exclusivity for AZEDRA.

In addition, exclusive marketing rights in the United States may be limited if we seek approval for an indication broader than the orphan-designated indication or may be lost if the FDA later determines that the request for designation was materially defective or if we are unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Even after an Orphan Drug is approved, the FDA can

subsequently approve the same drug with the same active moiety for the same condition if the FDA concludes that the later drug is safer, more effective or makes a major contribution to patient care.

Even after an Orphan Drug is approved, the FDA can subsequently approve the same drug with the same active moiety for the same condition if the FDA concludes that the later drug is safer, more effective or makes a major contribution to patient care.

A loss of the Orphan Drug exclusivity for AZEDRA may have an adverse impact on our ability to adequately commercialize AZEDRA.

Our just-in-time manufacturing of radiopharmaceutical products relies on the timely receipt of radioactive raw materials and the timely shipment of finished goods, and any disruption of our supply or distribution networks could have a negative effect on our business.

Because a number of our radiopharmaceutical products, including our TechneLite generators and AZEDRA, rely on radioisotopes with limited half-lives, we must manufacture, finish and distribute these products on a just-in-time basis, because the underlying radioisotope is in a constant state of radio decay.

Our just-in-time manufacturing of radiopharmaceutical products relies on the reliability of our equipment and processes and the timely receipt of radioactive raw materials and the timely shipment of finished goods, and any disruption of our supply or distribution networks could have a negative effect on our business.

At our Somerset, New Jersey facility, we manufacture AZEDRA on a hot cell line.

As with all manufacturing facilities, equipment and infrastructure age and become subject to increasing maintenance and repair.

If we experience an event, including a labor dispute, natural disaster, fire, power outage, machinery breakdown, security problem, failure to meet regulatory requirements, product quality issue, technology transfer issue or other issue, we may be unable to manufacture the relevant products at previous levels or on the forecasted schedule, if at all.

Due to the stringent regulations and requirements of the governing regulatory authorities regarding the manufacture of our products, we may not be able to quickly restart manufacturing at our facilities or establish additional or replacement sources for certain products, components or materials.

In addition, because a number of our radiopharmaceutical products, including our TechneLite generators, PYLARIFY and AZEDRA, rely on radioisotopes with limited half-lives, we or our partners must manufacture, finish and distribute these products on a just-in-time basis, because the underlying radioisotope is in a constant state of decay.

For example, if we receive Mo-99 in the morning of a manufacturing day for TechneLite generators, then we will generally ship finished generators to customers by the end of that same business day.

Shipment of generators may be by next day delivery services or by either ground or air custom logistics.

Similarly, the radioisotope used in PYLARIFY is F 18, which has a 110 minute half-life, requiring that this product be manufactured and distributed within the same day 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.

Any delay in us receiving radioisotopes from suppliers or being able to have finished products delivered to customers because of weather or other unforeseen transportation issues could have a negative effect on our business, results of operations, financial condition and cash flows.

In the U.S., we are heavily dependent on a few large customers to generate a majority of our revenues for our nuclear medical imaging products.

In the U.S., we are heavily dependent on a few large customers to generate a majority of our revenues for our nuclear medical imaging products in our precision diagnostic product category.

Outside of the U.S., we rely primarily on distributors to generate a substantial portion of our revenue.

In the U.S., we have historically relied on a limited number of radiopharmacy customers, primarily Cardinal, RLS, UPPI, Jubilant Radiopharma and PharmaLogic, to distribute our current largest volume nuclear imaging products.

In the U.S., we have historically relied on a limited number of radiopharmacy customers, primarily Cardinal, Jubilant Radiopharma, PharmaLogic, RLS and UPPI, to purchase our current largest volume nuclear imaging products.

Among the existing radiopharmacies in the U.S., continued consolidations, divestitures and reorganizations may have a negative effect on our business, results of operations, financial condition and cash flows.

We generally have distribution arrangements with our major radiopharmacy customers pursuant to multi-year contracts, each of which is subject to renewal.

If these contracts are terminated prior to expiration of their term, or are not renewed, or are renewed on terms that are less favorable to us, then such an event could have a material adverse effect on our business, results of operations, financial condition and cash flows.

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 generally are 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.

If these contracts are terminated prior to the expiration of their term, or are not renewed, or are renewed on terms that are less favorable to us, then such an event could have a material adverse effect on our business, results of operations, financial condition and cash flows.

For all of our medical imaging products, we continue to experience significant pricing pressures from our competitors, large customers and group purchasing organizations, and any significant, additional pricing pressures could lead to a reduction in revenue which could have a material adverse effect on our business, results of operations, financial condition and cash flows.

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and Canada, we have no sales force and, consequently, rely on third party distributors, either on a country-by-country basis or on a multi-country, regional basis, to market, sell and distribute our products.

In Canada, we maintain our own direct sales force to sell DEFINITY.

In Canada, we maintain our own direct sales force to generate sales of DEFINITY.

In certain circumstances, distributors may also sell competing products to our own or products for competing diagnostic modalities and may have incentives to shift sales towards those competing products.

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

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

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

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

• For PYLARIFY, our competitors currently include Telix Pharmaceuticals Limited and Bracco, and may in the future include 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.

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.

• For RELISTOR, our principal competitors include Nektar Therapeutics, in collaboration with AstraZeneca PLC;

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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.

• 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 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.

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most of the serious but non-fatal reactions also occurred in this time frame.

As a result, in October 2007, the FDA requested that we and GE Healthcare, which distributes Optison, a competitor to DEFINITY, add a boxed warning to these products emphasizing the risk for serious cardiopulmonary reactions and that the use of these products was contraindicated in certain patients.

contraindicated in certain patients.

In a strong reaction by the cardiology community to the FDA’s new position, a letter was sent to the FDA, signed by 161 doctors, stating that the benefit of these ultrasound enhancing agents outweighed the risks and urging that the boxed warning be removed.

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Bracco’s ultrasound enhancing agent, Lumason, has substantially similar safety labeling as DEFINITY and Optison.

In April 2021, after reviewing certain adverse events that occurred in patients with a prior history of allergic reactions to polyethylene glycol (“PEG”), an inactive excipient in both DEFINITY and Lumason, the FDA and the marketing authorization holders of these products agreed to an additional contraindication for use of these products, including advising clinicians to assess patients for prior PEG hypersensitivity before administering these products.

If additional safety issues arise (not only with DEFINITY but also potentially with Optison and Lumason), this may result in unfavorable changes in labeling or result in restrictions on the approval of our product, including removal of the product from the market.

Lingering safety concerns about DEFINITY among some healthcare providers or future unanticipated side effects or safety concerns associated with DEFINITY could limit expanded use of DEFINITY and have a material adverse effect on the unit sales of this product and our financial condition and results of operations.

Risks Related to our Portfolio of Clinical Development Candidates

The process of developing new drugs and obtaining regulatory approval is complex, time-consuming and costly, and the outcome is not certain.

We currently have two active clinical development programs in the U.S.

– PyL and 1095.

We also have a number of strategic partnerships relating to obtaining additional indications for existing commercial products or regulatory approval for clinical development candidates.

To obtain regulatory approval for these agents in the indications being pursued, we must conduct extensive human tests, which are referred to as clinical trials, as well as meet other rigorous regulatory requirements, as further described in Part I, Item 1.

“Business—Regulatory Matters.” Satisfaction of all regulatory requirements typically takes many years and requires the expenditure of substantial resources.

A number of other factors may cause significant delays in the completion of our clinical trials, including unexpected delays in the initiation of clinical sites, slower than projected enrollment, competition with ongoing clinical trials and scheduling conflicts with participating clinicians, regulatory requirements, limits on manufacturing capacity and failure of an agent to meet required standards for administration to humans.

In addition, it may take longer than we project to achieve study endpoints and complete data analysis for a clinical trial or we may decide to slow down the enrollment in a trial in order to conserve financial resources.

Our agents in development are also subject to the risks of failure inherent in drug development and testing.

The results of preliminary studies do not necessarily predict clinical success, and larger and later stage clinical trials may not produce the same results as earlier stage trials.

Sometimes, agents that have shown promising results in early clinical trials have subsequently suffered significant setbacks in later clinical trials.

Agents in later stage clinical trials may fail to show desired safety and efficacy traits, despite having progressed through initial clinical testing.

In addition, the data collected from clinical trials of our agents in development may not be sufficient to support regulatory approval, or regulators could interpret the data differently and less favorably than we do.

Further, the design of a clinical trial can determine whether its results will support approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced.

Clinical trials of potential products often reveal that it is not practical or feasible to continue development efforts.

Regulatory authorities may require us or our partners to conduct additional clinical testing, in which case we would have to expend additional time and resources.

The approval process may also be delayed by changes in government regulation, future legislation or administrative action or changes in regulatory policy that occur prior to or during regulatory review.

The failure to provide clinical and preclinical data that are adequate to demonstrate to the satisfaction of the regulatory authorities that our agents in development are safe and effective for their proposed use will delay or preclude approval and will prevent us from marketing those products.

We are not permitted to market our agents in development in the U.S.

or other countries until we have received requisite regulatory approvals.

For example, securing FDA approval for a new drug requires the submission of an NDA to the FDA for our agents in development.

The NDA must include extensive nonclinical and clinical data and supporting information to establish the agent’s safety and effectiveness for each indication.

The NDA must also include significant information regarding the chemistry, manufacturing and controls for the product.

The FDA review process can take many years to complete, and approval is never guaranteed.

If a product is approved, the FDA may limit the indications for which the product may be marketed, require extensive warnings on the product labeling, impose restricted distribution programs, require expedited reporting of certain adverse events, or require costly ongoing requirements for post-marketing clinical studies and surveillance or other risk management measures to monitor the safety or efficacy of the agent.

Markets outside of the U.S.

also have requirements for approval of agents with which we must comply prior to marketing.

Obtaining regulatory approval for marketing of an agent in one country does not ensure we will be able to obtain regulatory approval in other countries, but a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory process in other countries.

Also, any regulatory approval of any of our products or agents in development, once obtained, may be withdrawn.

Approvals might not be granted on a timely basis, if at all.

Our lead agent in development, PyL, faces risks relating to regulatory approval.

Our lead agent in development is PyL TM (18F-DCFPyL), our PSMA-targeted PET imaging agent for prostate cancer.

We filed an NDA for PyL in September 2020.

The NDA was accepted by the FDA in December 2020, granted priority review, and assigned a PDUFA action date of May 28, 2021.

The PyL NDA is supported by data from two pivotal studies (OSPREY and CONDOR), designed to establish the safety and diagnostic performance of PyL imaging across the disease continuum of prostate cancer.

Results from OSPREY Cohort A demonstrated improvement in specificity and positive predictive value of PyL PET imaging over conventional imaging in men with high risk prostate cancer but did not meet one of the study’s primary endpoints for sensitivity.

OSPREY Cohort B and CONDOR studied men with prostate cancer in various disease states, including biochemical recurrent prostate cancer, hormone sensitive prostate cancer, non-metastatic castrate resistant prostate cancer, and metastatic castrate resistant prostate cancer.

OSPREY Cohort B demonstrated sensitivity in detecting metastatic lesions, while CONDOR, in patients with biochemical recurrent prostate cancer and non-informative baseline findings, demonstrated a high correct localization rate and high detection rate, including patients with low PSA values.

In the CONDOR study, 63.9% of patients had a change in intended disease management plans due to the PyL imaging results.

While we believe the results from these two studies, taken as a whole, demonstrate the ability of PyL to reliably detect and localize disease and could enable more appropriate patient management, if the FDA determines that these study results are not sufficient or convincing, we may not be able to obtain FDA approval to commercialize PyL in the U.S.

in 2021 and may have to perform additional clinical studies with PyL.

If that were to result, our business, results of operations, financial condition and cash flows could be adversely affected.

We can give no assurance that GE Healthcare will be successful with the further clinical development of flurpiridaz F 18.

In May 2015, we announced complete results from the first of two planned Phase 3 clinical trials for flurpiridaz F 18.

Although the development candidate appeared to be well-tolerated from a safety perspective and outperformed SPECT in a highly statistically significant manner in the co-primary endpoint of sensitivity and in the secondary endpoints of image quality and diagnostic certainty, flurpiridaz F 18 did not meet its other co-primary endpoint of non-inferiority for identifying subjects without disease.

In April 2017, we entered into the License Agreement with GE Healthcare for the continued Phase 3 development and worldwide commercialization of flurpiridaz F 18.

Under the License Agreement, GE Healthcare will, among other things, complete the worldwide development of flurpiridaz F 18 by conducting a second Phase 3 trial and pursue worldwide regulatory approvals.

We cannot assure any particular outcome from GE Healthcare’s continued Phase 3 development of the agent or from regulatory review of either our or their Phase 3 study of the agent, that any of the data generated in either our or their sponsored Phase 3 study will be sufficient to support an NDA approval, that GE Healthcare will only have to conduct the one additional Phase 3 clinical study prior to filing an NDA, or that flurpiridaz F 18 will ever be approved as a PET MPI imaging agent by the FDA.

Any failure or significant delay in completing clinical

trials for our product candidates or in receiving regulatory approval for the sale of our product candidates may harm our business and delay or prevent us from being able to generate additional future revenue from product sales.

Even if clinical development candidates receive regulatory approval, we can give no assurance that they can be successfully commercialized.

Even if our clinical development candidates proceed through their clinical trials and ultimately receive regulatory approval, there is no guarantee that an approved product can be manufactured in commercial quantities at a reasonable cost or that such a product will be successfully marketed or distributed.

The manufacturing, marketing and distribution of radiopharmaceuticals is complex.

Rather than being manufactured at our own facilities, both PyL and flurpiridaz F 18 will require the creation of a field-based network of specialized PET manufacturing facilities, or PMFs, with radioisotope-producing cyclotrons.

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

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

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

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

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

population within six months of product approval.

If we are delayed in our PyL commercial launch by FDA approval of our manufacturing sites or other challenges, our business, results of operations, financial condition and cash flows could be adversely affected.

In addition, in the case of both PyL and flurpiridaz F 18, obtaining adequate reimbursement will be critical, including not only coverage from Medicare, Medicaid, other government payors as well as private payors but also appropriate payment levels which adequately cover the substantially higher manufacturing and distribution costs associated with an F 18-based agent in comparison to a Tc-99m-based agent.

We can give no assurance, even if PyL and flurpiridaz F 18 obtain regulatory approval, that adequate reimbursement can be secured to allow the approved agents to become successfully commercialized.

We have been and expect to continue to be dependent on partners for the development of certain product candidates, which expose us to the risk of reliance on these partners.

In connection with our on-going development activities, we currently depend, and expect to continue to depend, on numerous collaborators.

For example, in addition to our collaboration with GE Healthcare on flurpiridaz F 18, we have collaborations with Bayer to develop and commercialize products using our PSMA antibody technology, with Curium for the development and commercialization of PyL in Europe, and with ROTOP for the development and commercialization of 1404 in Europe.

In addition, certain clinical trials for our product candidates may be conducted by government-sponsored agencies, and consequently will be dependent on governmental participation and funding.

These arrangements expose us to the same considerations we face when contracting with third parties for our own trials.

If any of our collaborators breach or terminate its agreement with us or otherwise fail to conduct successfully and in a timely manner the collaborative activities for which they are responsible, the preclinical or clinical development or commercialization of the affected product candidate or research program could be delayed or terminated.

We generally do not control the amount and timing of resources that our collaborators devote to our programs or product candidates.

We also do not know whether current or future collaboration partners, if any, might pursue alternative technologies or develop alternative products either on their own or in collaboration with others, including our competitors, as a means for developing treatments for the diseases or conditions targeted by our collaborative arrangements.

Our collaborators are also subject to similar development, regulatory, manufacturing, cyber-security and competitive risks as us, which may further impede their ability to successfully perform the collaborative activities for which they are responsible.

Setbacks of these types to our collaborators could have a material adverse effect on our business, results of operations and financial condition.

We depend on licenses from third parties for our rights to develop and commercialize certain product candidates.

If we fail to achieve milestone requirements or to satisfy other conditions, we may lose those rights under those license agreements, and our business, results of operations and financial condition could be adversely affected.

Many of our products or product candidates incorporate rights licensed by third parties -- for example, we license patent rights on RELISTOR from Wyeth LLC and on PyL from JHU.

We could lose the rights to develop or commercialize these products and product candidates if the related license agreement is terminated due to a breach by us or otherwise.

In addition, we are required to make substantial cash payments, achieve milestones and satisfy other conditions, including filing for and obtaining marketing approvals and introducing products, to maintain rights under our license agreements.

Due to the nature of these agreements and the uncertainties of development, we may not be able to achieve milestones or satisfy conditions to which we have contractually

committed, and as a result may be unable to maintain our rights under these licenses.

If we do not comply with our license agreements, the licensors may terminate them, which could result in our losing our rights to, and therefore being unable to commercialize, related products.

Risks Related to the Integration of the Progenics Acquisition

We may not be able to successfully integrate the Progenics business into our business and realize the anticipated benefits of the Progenics Acquisition.

The ultimate success of the Progenics Acquisition will depend on our ability to successfully combine the business of Progenics with our own and realize the anticipated benefits, including synergies, cost savings, innovation and operational efficiencies and revenue growth from the combination.

If we are unable to achieve these objectives within the anticipated time frame, or at all, the anticipated benefits may not be realized fully or at all, or may take longer to realize than expected, and the value of our common stock may suffer.

The Progenics Acquisition involves the continued integration of Progenics’ business into our existing business, which has been a complex, costly and time-consuming process.

The on-going integration may result in material challenges, including, without limitation:

• The diversion of management’s attention from ongoing business concerns and performance shortfalls at one or both of the companies;

• Managing a larger combined company;

• Maintaining employee morale and attracting, motivating and retaining management personnel and other key employees;

• Unanticipated risks to our integration plan including in connection with timing, talent, and the potential need for additional resources;

• New or previously unidentified manufacturing, regulatory, or research and development issues in the Progenics business;

• Retaining existing business and operational relationships and attracting new business and operational relationships;

• Unanticipated changes in federal or state laws or regulations;

• Unforeseen expenses or delays associated with the Progenics Acquisition.

Many of these factors are outside of our control and any one of them could result in delays, increased costs, decreases in the amount of expected revenues and diversion of management’s time and energy, which could materially affect our financial position, results of operations and cash flows.

Our future results may be adversely impacted if we do not effectively manage our expanded operations following the completion of the Progenics Acquisition.

Our combined business is now significantly larger and more complex than our business was immediately prior to the consummation of the Progenics Acquisition.

Our ability to successfully manage this combined business will depend upon our ability to continue to integrate the two separate businesses and manage the combined business with its increased scale and scope, and increased costs and complexity.

We may not be successful or may not realize the expected operating efficiencies, cost savings and other benefits previously disclosed.

The CVRs we issued as part of the Progenics Acquisition may result in substantial future payments and could divert the attention of our management.

As part of the consideration for the Progenics Acquisition, we issued CVRs to the stockholders of Progenics and holders of in-the-money Progenics equity awards entitling them to future cash payments of 40% of PyL net sales over $100.0 million in 2022 and over $150.0 million in 2023.

These payments could be substantial and could adversely impact our liquidity.

In addition, we are obligated to exercise a level of effort, expertise and resources consistent with those normally used in a medical diagnostics business similar to our size and resources with respect to developing, seeking regulatory approval for and commercializing a product of similar market potential at a similar stage in its development or product life to PyL.

We are also required to produce net sales statements for PyL that may be reviewed and challenged by CVR holders, with any disagreement to be resolved by an independent accountant.

These requirements could divert management time and resources and result in additional costs.

The financial analyses and forecasts considered by us and Progenics and their respective financial advisors in connection with the Progenics Acquisition may not be realized, which may adversely affect the market price of our common stock in the future.

In performing their financial analyses and rendering their opinions related to the Progenics Acquisition, each of the respective financial advisors to us and Progenics relied on, among other things, internal stand-alone financial analyses and forecasts as separately provided by us and Progenics.

These analyses and forecasts were prepared by, or as directed by, our management or the management of Progenics, as applicable.

None of these analyses or forecasts were prepared with a view towards public disclosure or compliance with the published guidelines of the SEC or U.S.

Generally Accepted Accounting Principles.

These projections are inherently based on various estimates and assumptions that are subject to the judgment of those preparing them.

These projections are also subject to significant economic, competitive, industry and other uncertainties and contingencies, all of which are difficult or impossible to predict and many of which are beyond our control and the control of Progenics.

We can give no assurance that our current or future financial condition or results of operations will be consistent with what was set forth in such analyses and forecasts, which could have an adverse impact on the market price of our common stock or our current or future financial position.

We expect to continue to incur substantial expenses related to the integration of the Progenics business with our business.

We have incurred, and expect to continue to incur, substantial expenses in connection with the integration of the Progenics business with our own.

There are a large number of processes, policies, procedures, operations, technologies and systems that have been, or must be, integrated, including purchasing, accounting and finance, sales, payroll, pricing, revenue management, marketing and benefits.

The substantial majority of these costs have been, and will continue to be, non-recurring expenses related to the Progenics Acquisition, facilities and systems consolidation costs.

We may also incur additional costs to maintain employee morale and to attract, motivate or retain management personnel or key employees.

Risks Related to Reimbursement and Regulation

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These third party payors exercise significant control over patient access and increasingly use their enhanced bargaining power to secure discounted rates and impose other requirements that may reduce demand for our products.

Our potential customers’ ability to obtain adequate reimbursement for products and services from these third party payors affects the selection of products they purchase and the prices they are willing to pay.

For example, certain radiopharmaceuticals, when used for non-invasive imaging of the perfusion of the heart for the diagnosis and management of patients with known or suspected coronary artery disease, are currently subject to a Medicare National Coverage Determination (“NCD”).

The NCD permits the coverage of such radiopharmaceuticals only when certain criteria are met.

Our partnered PET pipeline product flurpiridaz F 18, if approved, may become subject to this NCD, and may not be covered at all.

Our customers’ ability to obtain adequate reimbursement for products and services from these third party payors affects the selection of products they purchase and the prices they are willing to pay.

If Medicare and other third party payors do not provide adequate reimbursement for the costs of our products (or services provided using our products), deny the coverage of the products (or those services), or reduce current levels of reimbursement, healthcare professionals may not prescribe our products and providers and suppliers may not purchase our products.

In addition, demand for new products may be limited unless we obtain favorable reimbursement (including coverage, coding and payment) from governmental and private third party payors at the time of the product’s introduction, which will depend, in part, on our ability to demonstrate that a new agent has a positive impact on clinical outcomes.

In addition, demand for new products may be limited unless we obtain favorable reimbursement (including coding, coverage and payment) from governmental and private third party payors at the time of the product’s introduction, which will depend, in part, on our ability to demonstrate that a new agent has a positive impact on clinical outcomes.

Third party payors continually review their coverage policies for existing and new products and procedures and can deny coverage for procedures that include the use of our products or revise payment policies such that payments do not adequately cover the cost of our products.

Even if third party payors make coverage and reimbursement available, that reimbursement may not be adequate or these payors’ reimbursement policies may have an adverse effect on our business, results of operations, financial condition and cash flows.

For example, effective January 1, 2022, the CMS granted TPT Status in the hospital outpatient setting for PYLARIFY, enabling traditional Medicare to provide an incremental payment for PET/CT scans performed with PYLARIFY in that setting.

TPT Status for PYLARIFY is expected to expire 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.

The Company 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.

Over the past several years, Medicare has implemented numerous changes to payment policies for imaging procedures in both the hospital setting and non-hospital settings (which include physician offices and freestanding imaging facilities).

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The ongoing and future impact of these changes cannot be determined at this time.

Medicare physician schedule payment rates may also be impacted by other Congressional policy priorities (e.g., annual updates ranging from 0% to 0.75% under the Medicare Access and CHIP Reauthorization Act of 2015, and a 3.75% increase in CY 2021 (intended to offset a portion of the widespread reductions in the Relative Value Units (RVUs) underlying rate calculations)

We believe that Medicare changes to payment policies for imaging procedures applicable to non-hospital settings will continue to result in certain physician practices ceasing to provide these services and a further shifting of where certain medical imaging procedures are performed, from the physician office and free-standing imaging facility settings to the hospital outpatient setting.

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Within the hospital outpatient setting, CMS payment policy is such that the use of many of our products are not separately payable by Medicare, although certain new drug products are eligible for separate (incremental) payment for the first three years after approval.

Since 2013, although Medicare generally does not provide separate payment to hospitals for the use of diagnostic radiopharmaceuticals administered in an outpatient setting, CMS has had a policy to make a nominal additional payment ($10) to hospitals that utilize products with non-HEU, meaning the product is 95% derived from non-HEU sources.

Although Medicare generally does not provide separate payment to hospitals for the use of diagnostic radiopharmaceuticals administered in an outpatient setting, since 2013, CMS has had a policy to make a nominal additional payment ($10) to hospitals that utilize products with non-HEU, meaning the product is 95% derived from non-HEU sources.

This payment policy continues in 2022.

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We also expect increased regulation and oversight of advanced diagnostic testing in which our products are used.

Beginning January 1, 2020, a professional who is ordering advanced diagnostic imaging services (which include MRI, CT, nuclear medicine (including PET) and other advanced diagnostic imaging services that the Secretary of HHS may specify, but not currently including echocardiography) must consult a qualified clinical decision support mechanism, as identified by HHS, to determine whether the ordered service adheres to specified appropriate use criteria (“AUC”).

Reimbursement penalties will apply in 2022 if this requirement is not met (and documented on the claim).

Under section 218(b) of the Protecting Access to Medicare Act, beginning January 1, 2020, a professional who is ordering advanced diagnostic imaging services (which include MRI, CT, nuclear medicine (including PET) and other advanced diagnostic imaging services that the Secretary of HHS may specify, but not currently including echocardiography) must consult a qualified clinical decision support mechanism, as identified by HHS, to determine whether the ordered service adheres to specified appropriate use criteria (“AUC”) developed or endorsed by CMS-qualified “provider led entities”.

Medicare claims for such services must include information indicating whether services ordered would adhere to specified applicable AUC.

Denial of claims for failure to include AUC consultation information on the claim form was set to begin on January 1, 2022.

In the CY 2022 Physician Fee Schedule Final Rule, CMS delayed the start of these claims denials until the later of January 1, 2023, or the January 1st that follows the declared end of the Public Health Emergency for COVID–19.

To the extent that these types of changes have the effect of reducing the aggregate number of diagnostic medical imaging procedures performed in the U.S., our business, results of operations, financial condition and cash flows would be adversely affected.

Medicare coverage of PET radiopharmaceuticals has been the subject of a large number of National Coverage Determinations (“NCDs”) by CMS since 2000.

Specific indications for PET imaging were covered, some through Coverage with Evidence Development.

CMS’s longtime policy, however, was that a particular use of PET scans is not covered unless an NCD specifically provided that such use was covered.

Effective March 7, 2013, CMS revised its policy through an NCD to allow local Medicare Administrative Contractors (“MACs”) to determine coverage within their respective jurisdictions for PET using radiopharmaceuticals for their FDA-approved labeled indications for oncologic imaging.

Effective January 1, 2022, non-coverage in the absence of an NCD has also been removed for non-oncologic indications of PET radiopharmaceuticals, allowing MACs to determine coverage for these indications within their respective jurisdictions.

To the extent that CMS or the MACs impose more restrictive coverage, our business, results of operations, financial condition and cash flows would be adversely affected.

Reforms to the U.S.

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Subsequently, the Medicare Access and CHIP Reauthorization Act of 2015 significantly revised the methodology for updating the Medicare physician fee schedule.

And more recently, Congress enacted legislation in 2017 that effectively eliminated the Healthcare Reform Act’s “individual mandate” beginning in 2019 Congress continues to consider other healthcare reform legislation.

And more recently, Congress enacted legislation in 2017 that effectively eliminated the Healthcare Reform Act’s “individual mandate” beginning in 2019.

Congress continues to consider other healthcare reform legislation.

There is no assurance that the Healthcare Reform Act, as currently enacted or as amended in the future, will not adversely affect our business and financial results, and we cannot predict how future federal or state legislative, judicial or administrative changes relating to healthcare reform will affect our business.

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These provisions have resulted in the imposition of 2% reductions in Medicare payments to providers, which went into effect on April 1, 2013 and will remain in effect through fiscal year 2030.

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

The CARES Act temporarily 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.

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, as part of any broader deficit reduction effort or legislative replacement to the Budget Control Act, could have an adverse impact on our business, results of operations, financial condition and cash flows.

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as well as non-U.S.

and transnational laws and regulations, with regulations differing from country to country, including, among other things, anti-trust and competition laws and regulations and the recently enacted General Data Protection Regulation (GDPR) in the European Union (the “EU”).

and transnational laws and regulations, with regulations differing from country to country, including, among other things, anti-trust and competition laws and regulations, and the General Data Protection Regulation in the European Union.

In the U.S., the FDA regulates, among other things, the pre-clinical testing, clinical trials, manufacturing, safety, efficacy, potency, labeling, storage, record keeping, quality systems, advertising, promotion, sale, distribution, and import and export of drug products.

We are required to register our business for permits and/or licenses with, and comply with the stringent requirements of the FDA, the NRC, the HHS, Health Canada, the EMA, the MHRA, the NMPA, state and provincial boards of pharmacy, state and provincial health departments and other federal, state and provincial agencies.

Violation of any of these regulatory schemes, individually or collectively, could disrupt our business and have a material adverse effect on our business, results of operations, financial condition and cash flows.

law, for example, we are required to report certain adverse events and production problems, if any, to the FDA.

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We must also report specific prices to government agencies under healthcare programs, such as the Medicaid drug rebate program and Medicare Part B.

As a specific example, in 2010, we entered into a Medicaid Drug Rebate Agreement with the federal government for some but not all of our products, and in 2016 entered into a separate Medicaid Drug Rebate Agreement for the balance of our products.

These agreements require us to report certain price information to the federal government.

Our Medicaid Drug Rebate agreements require us to report certain price information to the federal government.

Determination of the rebate amount that we pay to state Medicaid programs for our products, of prices charged to government and certain private payors for our products, or of amounts paid for our products under government healthcare programs, depends upon information reported by us to the government.

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• Withdrawals or suspensions of our current products from the market.

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

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

For example, on April 16, 2021 in the case Genus Medical Technologies LLC v.

Food and Drug Administration, the U.S.

Court of Appeals for the D.C.

Circuit held that a product (other than a combination product) that meets the definitions of both “drug” and “device” in the FDCA must be regulated as a device.

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 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.

Our marketing and sales practices may contain risks that could result in significant liability, require us to change our business practices, and restrict our operations in the future.

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If our operations are found to be in violation of these laws or any other government regulations that apply to us, we may be subject to penalties, including, without limitation, civil and criminal penalties, damages, fines, imprisonment, the curtailment or restructuring of our operations, or exclusion from state and federal healthcare programs including Medicare and Medicaid, any of which could have a material adverse effect on our business, results of operations, financial condition and cash flows.

Starting as of the end of fiscal 2019, we are required to maintain additional procedures and practices related to internal control over financial reporting, and we may identify deficiencies that we may not be able to remediate in time to meet the necessary deadline.

Pursuant to Section 404 of the Sarbanes-Oxley Act, our management is required to report upon the effectiveness of our internal control over financial reporting.

Since we are no longer an “emerging growth company” and are now a “large accelerated filer”, our independent registered public accounting firm is required to attest to the effectiveness of our internal controls on an annual basis, starting with our Annual Report on Form 10-K for the year ended December 31, 2019.

The rules governing the standards that must be met for our management and independent registered public accounting firm to assess our internal controls are complex and require significant documentation, testing and possible remediation of our existing controls and the incurrence of significant additional expenditures.

Any failure to implement required new or improved controls, or difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations.

In addition, any testing by us or our independent registered public accounting firm conducted in connection with Section 404 of the Sarbanes-Oxley Act may reveal deficiencies in our internal controls that are deemed to be material weaknesses or that may require prospective or retroactive changes to our financial statements or identify other areas for further attention or improvement.

Internal control deficiencies could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock.

Internal control deficiencies could also result in a restatement of our financial results in the future.

We could become subject to stockholder or other third party litigation, as well as investigations by the SEC or other regulatory authorities, which could require additional financial and management resources and could result in fines, trading suspensions, payment of damages or other remedies.

Further, any delay in compliance with the auditor attestation provisions of Section 404 could subject us to a variety of administrative sanctions, including ineligibility for short-form resale registration, action by the SEC and the suspension or delisting of our common stock, which could reduce the trading price of our common stock and could harm our business.

Risks Related to Our Business Operations and Financial Results

The COVID-19 pandemic has had, and could continue to have, a material impact on our business, results of operation and financial condition, operating results, cash flows and prospects.

In December 2019, a novel strain of coronavirus (COVID-19) emerged in Wuhan China.

Less than four months later, in March 2020, the World Health Organization declared COVID-19 a pandemic.

While the outbreak initially was largely concentrated in China and caused significant disruptions in its economy, the virus has now spread throughout much of the world, including in Massachusetts, New York, New Jersey, Canada and Sweden, where our offices and manufacturing facilities are located.

Towards the end of the first quarter of 2020 we began to experience, and through the date of this filing we are continuing to experience, impacts to our business and operations related to the COVID-19 pandemic, including the impact of stay-at-home mandates and advisories, and a decline in the volume of procedures using our products.

In response to the pandemic, healthcare providers have, and may need to further, reallocate resources, such as physicians, staff and facilities, as they prioritize limited resources and personnel

capacity to focus on the treatment of patients with COVID-19 and implement limitations on access to hospitals and other medical institutions due to concerns about the potential spread of COVID-19 in such settings.

In particular, there has been a reduction in the number of echocardiograms performed in 2020 (approximately 31.5 million) as compared to the number performed in 2019 (approximately 35.1 million), in each case, according to a third party source.

Towards the end of the first quarter of 2020 we began to experience, and through the date of this filing we are continuing to experience, impacts to our business and operations related to the COVID-19 pandemic, including the impact of hospital staffing challenges, vaccination mandates, employee absences due to illness, and a decline in the volume of procedures and treatments using our products.

In response to the pandemic, healthcare providers have, and may need to further, reallocate resources, such as physicians, staff and facilities, as they prioritize limited resources and personnel capacity to focus on the treatment of patients with COVID-19 and implement limitations on access to hospitals and other medical institutions due to concerns about the potential spread of COVID-19 in such settings.

Vaccination mandates may also create additional personnel and capacity constraints.

For example, we believe that during the fourth quarter of 2021 sales of DEFINITY were impacted by hospital nursing and sonographer shortages, and sales of AZEDRA were impacted by treatment capacity constraints in hospitals, treatment deferrals and cancellations by patients, and access restrictions by hospitals.

There has also been a reduction in pulmonary ventilation studies in which our Xenon is used because of institutional concerns and professional society guidelines relating to the possible spread of COVID-19 to technicians and other patients, given that Xenon is both inhaled and exhaled by the patient.

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We expect Xenon sales to continue to be at reduced levels so long as COVID-19 precautions remain in place.

Similarly, with respect to AZEDRA, the resurgence of COVID-19 infection rates impacted sales by creating treatment capacity constraints in hospitals, treatment deferrals and cancellations by patients and access restrictions by hospitals.

These actions have significantly delayed the provision of other medical care including procedures involving our products, having an adverse effect on our revenue.

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• A portion of our raw materials or finished product inventory may expire due to reduced demand for our drugs;

• Delays in our ability, and the ability of our contract research organizations and development partners to conduct, enroll and complete clinical development programs such as our ARROW Phase 2 study in mCRPC, the flurpiridaz F 18 Phase 3 clinical

development program currently being conducted by GE Healthcare, or the Phase 1 trial of PSMA TTC being conducted by Bayer AG;

• Delays of regulatory reviews and approvals, including with respect to our product candidates and manufacturing facilities, by the FDA or other health or regulatory authorities;

• Decreased sales of those of our products that are promotionally sensitive, like DEFINITY, due to the reduction of in-person sales and marketing activities and training caused by travel restrictions, quarantines, other similar social distancing measures and more restrictive hospital access policies;

• Decreased sales of those of our products that are promotionally sensitive, like DEFINITY and AZEDRA, due to the reduction of in-person sales and marketing activities and training caused by travel restrictions, quarantines, other similar social distancing measures and more restrictive hospital access policies;

• Our ability to maintain employee morale and motivate and retain management personnel and other key employees as a result of our previous work week and salary reductions;

• A disruption or delay in regulatory approval for, and operation of, our new, on-campus manufacturing facility, which would delay implementation of our supply diversification strategy for certain of our key products and impact our ability to benefit from a lower cost of goods for those products;

• A reduction in revenue with continued incurrence of high fixed costs relating to our already-existing, complex and expensive radiopharmaceutical manufacturing facility could adversely affect our cash flows, liquidity and ability to comply with the financial covenants in our 2019 Facility, and there can be no assurance that any required waiver or consent related to any such failure to comply would be granted by our current lenders similar to the waiver of total net leverage ratio in exchange for a consolidated liquidity covenant agreed to in June 2020;

• The increased reliance on our personnel working from home, which may negatively impact productivity, or disrupt, delay or otherwise adversely impact our business;

• A delay in achieving, or inability to achieve, successful integration of Lantheus and Progenics, or the synergies, cost savings, innovation and other anticipated benefits of the acquisition due to impact of the COVID-19 pandemic on the operations, financial condition and prospects of our Company;

• The instability to worldwide economies, financial markets, social institutions, labor markets and the healthcare systems as a result of the COVID-19 pandemic, which could result in an economic downturn that could adversely impact our business, results of operations and financial condition, as well as that of our suppliers, distributors, customers or other business partners;

• A recurrence of the COVID-19 pandemic after social distancing and other similar measures have been relaxed.

• A disruption in the operation of our new on-site manufacturing facility, which would delay implementation of our supply diversification strategy for DEFINITY and impact our ability to benefit from a lower cost of goods for that product;

• The increased reliance on our personnel working from home, which may negatively impact employee engagement, loyalty and productivity, or disrupt, delay or otherwise adversely impact our business, including through the increased employee resignations and retirements;

• The instability in worldwide economies, financial markets, social institutions, labor markets and the healthcare systems as a result of the COVID-19 pandemic, which could result in an economic downturn that could adversely impact our business, results of operations and financial condition, as well as that of our suppliers, distributors, customers or other business partners;

• A recurrence of the COVID-19 pandemic, or the development and spread of new strains of COVID-19 after social distancing and other similar measures have been relaxed.

The extent to which the COVID-19 pandemic impacts our business and our results of operations and financial condition will depend on future developments that are highly uncertain and cannot be predicted, including new information that may emerge in connection with the severity of the virus, the ability to treat and ultimately prevent it with vaccines, its potential recurrence or transformation into new or more contagious or virulent strains, and further actions that federal, state, local, or foreign governments may take to contain its impact.

We may not be able to hire or retain the number of qualified personnel, particularly scientific, medical and sales personnel, required for our business, which would harm the development and sales of our products and limit our ability to grow.

Competition in our industry for highly skilled scientific, healthcare and sales personnel is intense.

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

Although we were successful in hiring and onboarding those employees and we have not had any material difficulty in the past in hiring or retaining qualified personnel, if we are unable to retain our existing personnel, or attract and train additional qualified personnel, either because of competition in our industry for these personnel, prolonged remote working conditions due to the COVID-19 pandemic, or insufficient financial resources, then our growth may be limited and it could have a material adverse effect on our business.

If we lose the services of our key personnel, our business could be adversely affected.

Our success is substantially dependent upon the performance, contributions and expertise of our chief executive officer, executive leadership and senior management team.

Mary Anne Heino, our Chief Executive Officer and President, and other members of our executive leadership and senior management team play a significant role in formulating and executing on our long-term strategy, generating business and overseeing operations.

We have an employment agreement with Ms.

Heino and a limited number of other individuals on our executive leadership team, although we cannot prevent them from terminating their employment with us.

We do not maintain key person life insurance policies on any of our executive officers.

While we have experienced some turnover on our executive leadership team, we have generally been able to fill positions by either promoting existing employees or attracting new, qualified individuals to lead key functional areas.

Our inability to retain our existing executive leadership and senior management team, maintain an appropriate internal succession program or attract and retain additional qualified personnel could have a material adverse effect on our business.

Our business depends on our ability to successfully introduce new products and adapt to a changing technology and medical practice landscape.

The healthcare industry is characterized by continuous technological development resulting in changing customer preferences and requirements.

The success of new product development depends on many factors, including our ability to fund development of new agents or new indications for existing agents, anticipate and satisfy customer needs, obtain regulatory approval on a timely basis based on performance of our agents in development versus their clinical study comparators, develop and manufacture products in a cost-effective and timely manner, maintain advantageous positions with respect to intellectual property and differentiate our products from our competitors.

The success of new product development depends on many factors, including our ability to fund development of new agents or new indications for existing agents, anticipate and satisfy customer needs, obtain timely regulatory approval based on performance of our agents in development versus their clinical study comparators, develop and manufacture products in a cost-effective and timely manner, maintain advantageous positions with respect to intellectual property and differentiate our products from our competitors.

To compete successfully in the marketplace, we must make substantial investments in new product development, whether internally or externally through licensing or acquisitions.

Our failure to introduce new and innovative products in a timely manner would have an adverse effect on our business, results of operations, financial condition and cash flows.

Even if we are able to develop, manufacture and obtain regulatory approvals for our new products, the success of these products would depend upon market acceptance and adequate reimbursement.

Even if we are able to develop, manufacture and obtain regulatory approvals for our new products, the success of these products would depend upon market acceptance and adequate coding, coverage and payment.

Levels of market acceptance for our new products could be affected by a number of factors, including:

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• The timing of our market entry;

• Our ability to enter into commercial contracts to sell our products;

• Our ability to market and distribute our products effectively;

• Market acceptance of our products;

• Our ability to obtain adequate reimbursement.

The field of diagnostic medical imaging is dynamic, with new products, including hardware, software and agents, continually being developed and existing products continually being refined.

• Our ability to obtain adequate coding, coverage and payment.

The field of diagnostic medical imaging is dynamic, with new products, including equipment, software and products, continually being developed and existing products continually being refined.

Our own diagnostic imaging agents compete not only with other similarly administered imaging agents but also with imaging agents employed in different and often competing diagnostic modalities, and in the case of DEFINITY, echocardiography procedures without ultrasound enhancing agents.

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In addition, in the event of accidental contamination or injury from these materials, we could be held liable for any damages that result and any such liability could exceed our resources.

We currently lease a small portion of our North Billerica, Massachusetts facility to PerkinElmer for the manufacturing, finishing and packaging of certain radioisotopes, including Strontium-90, which has physical characteristics that make it more challenging to work with and dispose of than our own commercial radioisotopes, including a much longer half-life.

We previously leased a small portion of our North Billerica, Massachusetts facility to PerkinElmer for the manufacturing, finishing and packaging of certain radioisotopes, including Strontium-90, which has physical characteristics that make it more challenging to work with and dispose of than our own commercial radioisotopes, including a much longer half-life.

PerkinElmer decommissioned its space and vacated the premises as of December 30, 2021.

We are fully indemnified by PerkinElmer under our lease for any property damage or personal injury resulting from their activities in our facility.

If any release or excursion of radioactive materials took place from their leased space that resulted in property damage or personal injury, the indemnification obligations were not honored, and we were forced to cover any related remediation, clean-up or other expenses,

depending on the magnitude, the cost of such remediation, clean-up or other expenses could have a material adverse effect on our business, results of operations, financial condition and cash flows.

If any release or excursion of radioactive materials took place from their leased space that resulted in property damage or personal injury, the indemnification obligations were

not honored, and we were forced to cover any related remediation, clean-up or other expenses, depending on the magnitude, the cost of such remediation, clean-up or other expenses could have a material adverse effect on our business, results of operations, financial condition and cash flows.

While we have budgeted for current and future capital and operating expenditures to maintain compliance with these laws and regulations, we cannot assure you that our costs of complying with current or future environmental, health and safety laws and regulations will not exceed our estimates or adversely affect our results of operations and financial condition.

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• Our issued patents may not provide a basis for commercially viable drugs, may not provide us with any protection from unauthorized use of our intellectual property by third parties, and may not provide us with any competitive advantages;

• Our patent applications or patents may be subject to interferences, oppositions, post-grant review, ex-parte re-examinations, inter partes review or similar administrative proceedings;

• The validity or enforceability of our patent applications or patents may be subject to challenge through interferences, oppositions, post-grant review, ex-parte re-examinations, inter partes review or similar administrative proceedings;

• While we generally apply for patents in those countries where we intend to make, have made, use or sell patented products, we may not be able to accurately predict all of the countries where patent protection will ultimately be desirable and may be precluded from doing so at a later date;

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If we are not able to enforce and defend the patents of our technologies and products, then we will not be able to exclude competitors from marketing products that directly compete with our products, which could have a material and adverse effect on our business, results of operations, financial condition and cash flows.

For DEFINITY, our highest revenue and highest margin commercial product in 2020, we continue to actively pursue patents in both the U.S.

For DEFINITY, we continue to actively pursue patents in both the U.S.

and internationally.

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

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

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

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

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

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

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It is possible that a competitor will make use of that information, and that our competitive position will be compromised, in spite of any legal action we might take against persons making those unauthorized disclosures, which could have a material and adverse effect on our business, results of operations, financial condition and cash flows.

We rely on our trademarks, trade names and brand names to distinguish our products from the products of our competitors, and have registered or applied to register many of these trademarks, including, among others, DEFINITY ® , TechneLite ® , Cardiolite ® , NEUROLITE ® , VIALMIX ® , QUADRAMET ® , Luminity ® , PyL TM , AZEDRA ® , AZEDRA Service Connection ® , RELISTOR ® , Progenics ® , Progenics Pharmaceuticals ® , EXINI ® , Molecular Insight ® , Find, Fight and Follow ® , PyL Research Access Program ® , and Lantheus Medical Imaging ® .

We rely on our trademarks, trade names and brand names to distinguish our products from the products of our competitors, and have registered or applied to register many of these trademarks, including, among others, AZEDRA ® , AZEDRA Service Connection ® , Cardiolite ® , DEFINITY ® , DEFINITY RT TM , EXINI ® , Find, Fight and Follow ® , Find > Fight > Follow TM , Lantheus ® , Lantheus Medical Imaging ® , LUMINITY ® , Molecular Insight ® , NEUROLITE ® , Progenics ® , Progenics Pharmaceuticals ® , PYLARIFY ® , TechneLite ® , VIALMIX ® , and VIALMIX RFID ® .

We cannot assure you that any pending trademark applications will be approved.

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Our patents may be challenged, invalidated, held to be unenforceable, or circumvented, which could negatively impact their commercial value.

For example, Progenics (along with Bausch and Wyeth LLC) received notifications of a Paragraph IV certification for RELISTOR subcutaneous injection and for RELISTOR Tablets, for certain patents that are listed in the FDA Orange Book.

The certifications resulted from filings by entities such as Mylan Pharmaceuticals Inc., Actavis LLC and Par Sterile Products, LLC of ANDAs with the FDA, challenging such patents for RELISTOR subcutaneous injection and seeking to obtain approval to market a generic version of RELISTOR subcutaneous injection and filings by Actavis Laboratories FL, Inc.

seeking to obtain approval to market a generic version of RELISTOR Tablets before some or all of these patents expire.

Furthermore, patent applications filed outside the United States may be challenged by other parties, for example, by filing third party observations that argue against patentability or an opposition.

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Pursuant to the RELISTOR license agreement between us and Bausch, Bausch has the first right to enforce the intellectual property rights at issue and is responsible for the costs of such enforcement.

At the same time, we may incur substantial further costs

in supporting the effort to uphold the validity of patents or to prevent infringement.

At the same time, we may incur substantial further costs in supporting the effort to uphold the validity of patents or to prevent infringement.

Patent disputes are frequent, costly and can preclude, delay or increase the cost of commercialization of products.

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Our business is subject to international economic, political and other risks that could negatively affect our results of operations or financial position.

For the year ended December 31, 2020, we derived approximately 13.1% of our revenues from outside the fifty United States.

For the year ended December 31, 2021, we derived approximately 10% of our revenues and expended approximately 25% of our costs of goods sold outside of the fifty United States.

Accordingly, our business is subject to risks associated with doing business internationally, including:

• Less stable political and economic environments and changes in a specific country’s or region’s political or economic conditions;

• Less stable political and economic environment and changes in a specific country’s or region’s political or economic conditions;

• Changes in trade policies, regulatory requirements and other barriers, including, for example, U.S.

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• Greater difficulties in managing and staffing non-U.S.

operations, including our EXINI operations in Sweden;

• The need to ensure compliance with the numerous in-country and international regulatory and legal requirements applicable to our business in each of these jurisdictions and to maintain an effective compliance program to ensure compliance with these requirements, including in connection with the GDPR in the EU;

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These factors are beyond our control.

The realization of any of these or other risks associated with operating outside the fifty United States could have a material adverse effect on our business, results of operations, financial condition and cash flows.

As our international exposure increases and as we execute our strategy of international expansion, these risks may intensify.

The realization of any of these or other risks associated with operating outside the United States could have a material adverse effect on our business, results of operations, financial condition and cash flows.

We face currency and other risks associated with international sales.

We generate revenue from export sales, as well as from operations conducted outside the fifty United States.

We generate revenue from export sales, as well as from operations conducted outside the United States.

Operations outside the U.S.

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A disruption in our computer networks, including those related to cybersecurity, could adversely affect our operations or financial position.

We rely on our computer networks and systems, some of which are managed by third parties, to manage and store electronic information (including sensitive data such as confidential business information and personally identifiable data relating to employees), and to manage or support a variety of critical business processes and activities.

We rely on our computer networks and systems, some of which are managed by third parties, to manage and store electronic information (including sensitive data such as confidential business information, personally identifiable data and personal health information), and to manage or support a variety of critical business processes and activities.

We may face threats to our networks from unauthorized access, security breaches and other system disruptions.

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As of December 31, 2021, we had U.S.

federal income tax loss carryforwards of $492.5 million, $354.5 million of which will begin to expire in 2021 and will completely expire in 2037, $138.0 million of which can be carried forward indefinitely, and state income tax loss carryforwards of $18.0, tax-effected.

federal income tax loss carryforwards of $476.2 million, $338.1 million of which will expire between 2022 and 2037, $138.0 million of which can be carried forward indefinitely, and state income tax loss carryforwards of $17.4 million, tax-effected.

We may be limited in our ability to use these tax loss carryforwards to reduce our future U.S.

federal and state income tax liabilities if our future income is not sufficient to absorb the losses, or if we were to experience another “ownership change” as specified in Section 382 of the Internal Revenue Code including if we were to issue a certain amount of equity securities, certain of our stockholders were to sell shares of our common stock, or we were to enter into certain strategic transactions.

Competition in our industry for highly skilled scientific, healthcare and sales personnel is intense.

Although we have not had any material difficulty in the past in hiring or retaining qualified personnel, if we are unable to retain our existing personnel, or attract and train additional qualified personnel, either because of competition in our industry for these personnel or because of insufficient financial resources, then our growth may be limited and it could have a material adverse effect on our business.

If we lose the services of our key personnel, our business could be adversely affected.

Our success is substantially dependent upon the performance, contributions and expertise of our chief executive officer, executive leadership and senior management team.

Mary Anne Heino, our Chief Executive Officer and President, and other members of our executive leadership and senior management team play a significant role in generating new business and retaining existing customers.

We have an employment agreement with Ms.

Heino and a limited number of other individuals on our executive leadership team, although we cannot prevent them from terminating their employment with us.

We do not maintain key person life insurance policies on any of our executive officers.

While we have experienced both voluntary and involuntary turnover on our executive leadership team, to date we have been able to attract new, qualified individuals to lead our company and key functional areas.

We are involved in various legal proceedings that are uncertain, costly and time-consuming and could have a material adverse impact on our business, financial condition and results of operations.

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In addition, in the U.S., it has become increasingly common for patent infringement actions to prompt claims that antitrust laws have been violated during the prosecution of the patent or during litigation involving the defense of that patent.

Such claims by direct and indirect purchasers and other payers are typically filed as class actions.

Such claims by direct

and indirect purchasers and other payors are typically filed as class actions.

The relief sought may include treble damages and restitution claims.

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A successful antitrust claim by a private party or government entity against us could have a material adverse effect on our business, financial condition and results of operations and could cause the market value of our common stock to decline.

Risks Related to our Portfolio of Clinical Development Candidates

The process of developing new drugs and obtaining regulatory approval is complex, time-consuming and costly, and the outcome is not certain.

We currently have two clinical development programs in the U.S.

– 1095 and LMI 1195, and are exploring additional lifecycle management opportunities for some of our current products, including AZEDRA.

We also have a number of strategic partnerships relating to obtaining additional indications for existing commercial products or regulatory approval for clinical development candidates.

“Business—Regulatory Matters.” Satisfaction of all regulatory requirements typically takes many years and requires the expenditure of substantial resources.

Our products in development are also subject to the risks of failure inherent in drug development and testing.

The results of preliminary studies do not necessarily predict clinical success, and larger and later stage clinical trials may not produce the same results as earlier stage trials.

Sometimes, products that have shown promising results in early clinical trials have subsequently suffered significant setbacks in later clinical trials.

Agents in later stage clinical trials may fail to show desired safety and efficacy traits, despite having progressed through initial clinical testing.

In addition, the data collected from clinical trials of our products in development may not be sufficient to support regulatory approval, or regulators could interpret the data differently and less favorably than we do.

Clinical trials of potential products often reveal that it is not practical or feasible to continue development efforts.

Regulatory authorities may require us or our partners to conduct additional clinical testing, in which case we would have to expend additional time and resources.

The failure to provide clinical and preclinical data that are adequate to demonstrate to the satisfaction of the regulatory authorities that our products in development are safe and effective for their proposed use will delay or preclude approval and will prevent us from marketing those products.

We are not permitted to market our products in development in the U.S.

or other countries until we have received requisite regulatory approvals.

For example, securing FDA approval for a new drug requires the submission of an NDA to the FDA for our products in development.

The NDA must include extensive nonclinical and clinical data and supporting information to establish the product’s safety and effectiveness for each indication.

The NDA must also include significant information regarding the chemistry, manufacturing and controls for the product.

The FDA review process can take many years to complete, and approval is never guaranteed.

Markets outside of the U.S.

also have requirements for approval of products with which we must comply prior to marketing.

Obtaining regulatory approval for marketing of a product in one country does not ensure we will be able to obtain regulatory approval in other countries, but a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory process in other countries.

Also, any regulatory approval of any of our products in development, once obtained, may be withdrawn.

Approvals might not be granted on a timely basis, if at all.

We can give no assurance that GE Healthcare will be successful with the further clinical development of flurpiridaz F 18.

In May 2015, we announced complete results from the first of two planned Phase 3 clinical trials for flurpiridaz F 18.

In April 2017,

we entered into the License Agreement with GE Healthcare for the continued Phase 3 development and worldwide commercialization of flurpiridaz F 18.

Any failure or significant delay in completing clinical trials for our product candidates or in receiving regulatory approval for the sale of our product candidates may harm our business and delay or prevent us from being able to generate additional future revenue from product sales.

Even if clinical development candidates receive regulatory approval, we can give no assurance that they can be successfully commercialized.

For example, the manufacturing, marketing and distribution of a radiopharmaceutical like flurpiridaz F 18 will require the creation of a field-based network of specialized PET manufacturing facilities, or PMFs, with radioisotope-producing cyclotrons, similar to what we created for PYLARIFY, and will need to be manufactured and distributed rapidly to end-users.

In addition, obtaining adequate coding, coverage and payment at appropriate payment levels for any clinical development candidate will be critical, including not only coverage from Medicare, Medicaid, and other government payors, but also from private payors.

We can give no assurance, even if a clinical development candidate were to obtain regulatory approval, that adequate coding, coverage and payment could be secured to allow the approved products to become successfully commercialized.

We have been and expect to continue to be dependent on partners for the development of certain product candidates, which expose us to the risk of reliance on these partners.

In connection with our ongoing development activities, we currently depend, and expect to continue to depend, on numerous collaborators.

For example, in addition to our collaboration with GE Healthcare on flurpiridaz F 18, we have collaborations with Bayer to develop and commercialize products using our PSMA antibody technology, with Curium for the development and commercialization of PYLARIFY in Europe, and with ROTOP for the development and commercialization of 1404 in Europe.

In addition, certain clinical trials for our product candidates may be conducted by government-sponsored agencies, and consequently will be dependent on governmental participation and funding.

These arrangements expose us to the same considerations we face when contracting with third parties for our own trials.

We generally do not control the amount and timing of resources that our collaborators devote to our programs or product candidates.

Setbacks of these types to our collaborators could have a material adverse effect on our business, results of operations and financial condition.

We depend on licenses from third parties for our rights to develop and commercialize certain product candidates.

Many of our products or product candidates incorporate rights licensed by third parties -- for example, we license patent rights on PYLARIFY from JHU and on RELISTOR from Wyeth LLC.

We could lose the rights to develop or commercialize these products and product candidates if the related license agreement is terminated due to a breach by us or otherwise.

Due to the nature of these agreements and the uncertainties of development, we may not be able to achieve milestones or satisfy conditions to which we have contractually committed, and as a result may be unable to maintain our rights under these licenses.

If we do not comply with our license agreements, the licensors may terminate them, which could result in our losing our rights to, and therefore being unable to commercialize, related products.

This loss could have a material adverse effect on our business, results of operations and financial condition.

Risks Related to Our Capital Structure

We have a substantial amount of indebtedness which may limit our financial and operating activities and may adversely affect our ability to incur additional debt to fund future needs.

We have indebtedness which may limit our financial and operating activities and may adversely affect our ability to incur additional debt to fund future needs.

As of December 31, 2021, we had approximately $175.0 million of total principal indebtedness remaining under our five‑year secured term loan facility, which matures on June 30, 2024 (the “2019 Term Facility” and the loans thereunder, the “2019 Term Loans”) and availability of $200.0 million under our five-year revolving credit facility (the “2019 Revolving Facility” and, together with the 2019 Term Facility, the “2019 Facility”).

As of December 31, 2020, we had approximately $32.6 million of total principal indebtedness remaining on our royalty-backed loan, which matures on June 30, 2025.

Our substantial indebtedness and any future indebtedness we incur could:

• Require us to dedicate a substantial portion of cash flow from operations to the payment of interest on and principal of our indebtedness, thereby reducing the funds available for other purposes;

Our indebtedness and any future indebtedness we incur could:

• Require us to dedicate a substantial portion of cash flow from operations to the payment of interest on and principal of our indebtedness, thereby reducing the funds available for other purposes, including for working capital, capital expenditures and acquisitions;

• Make it more difficult for us to satisfy and comply with our obligations with respect to our outstanding indebtedness, namely the payment of interest and principal;

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In addition, our substantial level of indebtedness could limit our ability to obtain additional financing on acceptable terms, or at all, for working capital, capital expenditures and general corporate purposes.

Our liquidity needs could vary significantly and may be affected by general economic conditions, industry trends, performance and many other factors not within our control.

Our liquidity needs could vary significantly and may be affected by general economic conditions, industry trends, performance and many other factors outside our control.

We may not be able to generate sufficient cash flow to meet our debt service obligations.

Our ability to generate sufficient cash flow from operations to make scheduled payments on our debt obligations will depend on our future financial performance, which will be affected by a range of economic, competitive and business factors, many of which are outside of our control.

If we do not generate sufficient cash flow from operations to satisfy our debt obligations, including interest and principal payments, our credit ratings could be downgraded, and we may have to undertake alternative financing plans, such as refinancing or restructuring our debt, selling assets, entering into additional corporate collaborations or licensing arrangements for one or more of our products or agents in development, reducing or delaying capital investments or seeking to raise additional capital.

If we do not generate sufficient cash flow from operations to satisfy our debt obligations, including interest and principal payments, our credit ratings could be downgraded, and we may have to undertake alternative financing plans, such as refinancing or restructuring our debt, selling assets, entering into additional corporate collaborations or licensing arrangements for one or more of our products in development, reducing or delaying capital investments or seeking to raise additional capital.

We cannot assure you that any refinancing would be possible, that any assets could be sold, licensed or partnered, or, if sold, licensed or partnered, of the timing of the transactions and the amount of proceeds realized from those transactions, that additional financing could be obtained on acceptable terms, if at all, or that additional financing would be permitted under the terms of our various debt instruments then in effect.

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Our inability to generate sufficient cash flow to satisfy our debt obligations, or to refinance our obligations on commercially reasonable terms or on a timely basis, would have an adverse effect on our business, results of operations and financial condition.

Despite our substantial indebtedness, we may incur more debt, which could exacerbate the risks described above.

Despite our indebtedness, we may incur more debt, which could exacerbate the risks described above.

We and our subsidiaries may be able to incur substantial additional indebtedness in the future subject to the limitations contained in the agreements governing our debt, including the 2019 Facility.

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If we or our subsidiaries incur additional debt, the risks that we and they now face as a result of our leverage could intensify.

In addition, 2019 Facility will not prevent us from incurring obligations that do not constitute indebtedness under the agreements.

In addition, the 2019 Facility will not prevent us from incurring obligations that do not constitute indebtedness under the agreements.

Our 2019 Facility contains restrictions that will limit our flexibility in operating our business.

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We may also be unable to take advantage of business opportunities that arise because of the limitations imposed on us by the restrictive covenants under our indebtedness.

If LIBOR is phased out, as anticipated, starting at the beginning of 2022, we will need to agree to a replacement index rate to be used under our 2019 Facility, which may have an adverse effect on our financial condition.

At present LIBOR is expected to be published only on a limited basis after 2021.

As LIBOR is phased out, as anticipated, we will need to agree to a replacement index rate to be used under our 2019 Facility, which may have an adverse effect on our financial condition.

The use of LIBOR, as it relates to the Company’s 2019 Term Facility, is expected to be phased out by the end of June 2023.

The 2019 Facility does not specify a particular “hard-wired” replacement index rate (or related margin) when LIBOR becomes unavailable, but relies on the administrative agent and the Company reaching agreement on such a replacement rate (and related margin) that gives due consideration to the then prevailing market convention for determining rates of interest for syndicated loans denominated in U.S.

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If interest rates increase, our interest expense could increase, affecting earnings and reducing cash flows available for working capital, capital expenditures and acquisitions.

The CVRs we issued as part of the Progenics Acquisition may result in substantial future payments to the holders of the CVRs;

in addition, the actual payments made in connection with the CVRs, if any, may not be consistent with the estimated fair value of the CVRs that we are required to prepare for accounting purposes.

As part of the consideration for the Progenics Acquisition, we issued CVRs to the stockholders of Progenics and holders of in-the-money Progenics equity awards entitling them to future cash payments of 40% of PYLARIFY net sales over $100.0 million in 2022 and over $150.0 million in 2023, subject to an aggregate cap.

These payments could be substantial.

In addition, we are obligated to exercise a level of effort, expertise and resources consistent with those normally used in a medical diagnostics business similar to our size and resources with respect to commercializing a product of similar market potential at a similar stage in its product life to PYLARIFY.

We are also required to produce net sales statements for PYLARIFY that may be reviewed and challenged by CVR holders, with any disagreement to be resolved by an independent accountant.

Because the CVRs are considered contingent consideration liabilities, for accounting purposes we are required by accounting principles generally accepted in the U.S.

to estimate their fair value on a recurring basis.

Adjustments in the estimated fair value of the CVRs can impact our consolidated financial statements on a quarterly or annual basis.

The estimated fair value of the CVRs is determined based on a Monte Carlo simulation model that includes significant estimates and assumptions pertaining to commercialization events, sales targets, market conditions and discount rates.

These estimates and assumptions are subject to the judgment of our management team and are not prepared with a view towards public disclosure of projected sales.

Our sales targets are also subject to significant economic, competitive, industry and other uncertainties and contingencies, which are difficult to predict and in many cases are beyond our control.

We can give no assurance that the actual amounts paid, if any, in connection with the CVRs will be consistent with any recurring fair value estimate for such CVRs.

Our stock price could fluctuate significantly, which could cause the value of your investment to decline, and you may not be able to resell your shares at or above your purchase price.

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• Issuance of new or changed securities analysts’ reports or recommendations;

• Investor perceptions of us and the medical technology and pharmaceutical industries;

• Investor perceptions of us and the pharmaceutical and medical device industries;

• Sales, or anticipated sales, of large blocks of our stock;

• Acquisitions or introductions of new products or services by us or our competitors;

• Acquisitions or introductions of new products or services by us or our competitors, including our ongoing commercial launch of PYLARIFY;

• Positive or negative results from our clinical development programs;

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• Litigation and governmental investigations;

• Geopolitical events;

• Changing economic conditions.

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The trading market for our common stock will be influenced by the research and reports that industry or securities analysts publish about us or our business.

If one or more of these analysts cease coverage of our company or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.

Moreover, if one or more of the analysts who cover us downgrade our stock, or if our results of operations do not meet their expectations, our stock price could also decline.

If one or more of these analysts ceases coverage of our company or fails to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.

Moreover, if one or more of the analysts who cover us downgrades our stock, or if our results of operations do not meet their expectations, our stock price could also decline.

We do not anticipate paying any cash dividends for the foreseeable future.

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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 1A. Risk Factors