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Item 1. Business

2023-03-09 compared with 2022-03-21 · 137 added, 164 removed, 672 unchanged (31% of the section changed)

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We are a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer.

Our core objective is to leverage our proprietary phospholipid drug conjugate ™ (PDC™) delivery platform to develop PDCs that are designed to specifically target cancer cells and deliver improved efficacy and better safety as a result of fewer off-target effects.

Our core objective is to leverage our proprietary phospholipid ether drug conjugate ™ (PDC™) delivery platform to develop PDCs that are designed to specifically target cancer cells and deliver improved efficacy and better safety as a result of fewer off-target effects.

We believe that our PDC platform possesses the potential for the discovery and development of the next generation of cancer-targeting treatments, and we plan to develop PDCs both independently and through research and development collaborations.

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These services are designed to improve patients’ and their caregivers’ access to high quality care and innovative treatments for their cancer.

Our lead PDC therapeutic, iopofosine is a small-molecule PDC designed to provide targeted delivery of iodine-131 directly to cancer cells, while limiting exposure to healthy cells.

Our lead PDC therapeutic, iopofosine I 131 is a small-molecule PDC designed to provide targeted delivery of iodine-131 directly to cancer cells, while limiting exposure to healthy cells.

We believe this profile differentiates iopofosine from many traditional on-market treatments.

Iopofosine is currently being evaluated in the CLOVER-WaM Phase 2 pivotal study in patients with relapsed/refractory (r/r) WM, a Phase 2B study in r/r multiple myeloma (MM) patients and the CLOVER-2 Phase 1 study for a variety of pediatric cancers.

Iopofosine is currently being evaluated in the CLOVER-WaM Phase 2 pivotal study in patients with relapsed/refractory (r/r) WM, a Phase 2b study in r/r multiple myeloma (MM) patients and r/r central nervous system lymphoma (CNSL) and the CLOVER-2 Phase 1a study for a variety of pediatric cancers has concluded and a Phase 1b study in pediatric patients with high grade glioma is initiating.

As with all clinical trials, adverse events, serious adverse events or fatalities may arise during a clinical trial due to medical problems that may not be related to clinical trial treatments

The CLOVER-1 Phase 2 study met the primary efficacy endpoints from the Part A dose-finding portion, conducted in r/r B-cell malignancies.

The CLOVER-WaM Study is a pivotal registration study currently evaluating iopofosine in Bruton tyrosine kinase inhibitor (BTKi) failed or suboptimal response WM patients.

The CLOVER-1 Phase 2B study, where iopofosine remains under further evaluation in highly refractory MM patients, is ongoing.

The CLOVER-2 Phase 1 pediatric study is an open-label, sequential-group, dose-escalation study to evaluate the safety and tolerability of iopofosine in children and adolescents with relapsed or refractory malignant solid tumors (neuroblastoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma) and lymphoma or recurrent or refractory malignant brain tumors (high grade glioma, and glioblastoma, etc.) for which there are no standard treatments.

The study is being conducted internationally at seven leading pediatric cancer centers.

The CLOVER-WaM Study is a pivotal registration study currently evaluating iopofosine in WM patients that were r/r to two prior lines of therapy including Bruton tyrosine kinase inhibitor (BTKi) failed or suboptimal response WM patients.

The CLOVER-1 Phase 2b study, where iopofosine remains under further evaluation in highly refractory MM and CNSL patients, is ongoing.

The CLOVER-2 Phase 1a pediatric study was an open-label, sequential-group, dose-escalation study to evaluate the safety and tolerability of iopofosine in children and adolescents with relapsed or refractory malignant solid tumors (neuroblastoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma) and lymphoma or recurrent or refractory malignant brain tumors (high grade glioma, and glioblastoma, etc.) for which there are no standard treatments.

The study was conducted internationally at seven leading pediatric cancer centers.

The CLOVER-2 Phase 1b pediatric study will be an open-label, dose finding study evaluating the activity of iopofosine in children and adolescents with r/r malignant brain tumors (high grade gliomas).

Food and Drug Administration (FDA) granted iopofosine Fast Track Designation for lymphoplasmacytic lymphoma (LPL) and WM patients having received two or more prior treatment regimens, as well as r/r MM and r/r diffuse large B-cell lymphoma (DLBCL).

Orphan Drug Designations (ODDs) have been granted for LPL/WM, MM, neuroblastoma, soft tissue sarcomas including rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma.

Iopofosine was also granted Rare Pediatric Disease Designation

(RPDD) for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma.

Iopofosine was also granted Rare Pediatric Disease Designation (RPDD) for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma.

The European Commission granted ODD for r/r MM and WM.

Our product pipeline also includes one preclinical PDC chemotherapeutic program (CLR 1900) and several partnered PDC assets.

Additionally, in June 2020, the European Medicines Agency (EMA) granted us Small and Medium-Sized Enterprise (SME) status by the EMA’s Micro, Small and Medium-sized Enterprise office.

SME status allows us to participate in significant financial incentives that include a 90% to 100% EMA fee reduction for scientific advice, clinical study protocol design, endpoints and statistical considerations, quality inspections of facilities and fee waivers for selective EMA pre-and post-authorization regulatory filings, including orphan drug and PRIME designations.

We are also eligible to obtain EMA certification of quality and manufacturing data prior to review of clinical data.

Other financial incentives include EMA-provided translational services of all regulatory documents required for market authorization, further reducing the financial burden of the market authorization process.

Our product pipeline also includes one preclinical PDC chemotherapeutic program (CLR 1900), a PDC-based alpha-emitter radiotherapeutic series (CLR12120) and several partnered PDC assets.

The CLR 1900 Series is being developed for solid tumors with a payload that inhibit mitosis (cell division), a validated pathway for treating cancers.

We are evaluating the CLR 12120 series with both actinium and astatine as future targeted alpha therapies.

We have leveraged our PDC platform to establish three ongoing collaborations featuring four unique payloads and mechanisms of action.

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Our PDC platform is designed to provide selective delivery of a diverse range of oncologic payloads to cancerous cells, whether a hematologic cancer or solid tumor, a primary tumor, or a metastatic tumor and cancer stem cells.

The PDC platform’s mechanism of entry is designed not to rely upon specific cell surface epitopes or antigens as are required by other targeted delivery platforms.

Our PDC platform takes advantage of a metabolic pathway utilized by all tumor cell types in all stages of the tumor cycle.

Tumor cells modify specific regions on the cell surface as a result of the utilization of this metabolic pathway.

The PDC platform’s mechanism of entry is designed not to rely upon a specific cell surface epitope or antigen as are required by other targeted delivery platforms.

Our PDC platform takes advantage of a metabolic pathway utilized by nearly all tumor cell types in all stages of the tumor cycle.

Tumor cells modify the cell surface to create specific, highly organized microdomains as a result of the utilization of this metabolic pathway.

Our PDCs are designed to bind to these regions and directly enter the intracellular compartment.

This mechanism allows the PDC molecules to accumulate in tumor cells over time, which we believe can enhance drug efficacy, and to avoid the specialized highly acidic cellular compartment known as lysosomes, which allows a PDC to deliver molecules that previously could not be delivered.

Additionally, molecules targeting specific cell surface epitopes face challenges in completely eliminating a tumor because the targeted antigens are limited in the total number on the cell surface, have longer cycling time from internalization to being present on the cell surface again and available for binding and are not present on all of the tumor cells in any cancer.

This mechanism allows the PDC molecules to accumulate in tumor cells over time, which we believe can enhance drug efficacy.

The direct intracellular delivery allows our molecules to avoid the specialized highly acidic cellular compartment known as lysosomes, which allows a PDC to deliver payloads that previously could not be delivered in this targeted manner.

Additionally, molecules targeting specific cell surface epitopes face challenges in completely eliminating a tumor because the targeted antigens are limited in the total number on the cell surface, have longer cycling time from internalization to being present on the cell surface again diminishing their availability for binding and are not present on all of the tumor cells because of the heterogenous nature of cancer cells.

This means a subpopulation of tumor cells always exist that cannot be targeted by therapies targeting specific surface epitopes.

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Our iterative process allows us to rapidly and systematically produce multiple generations of incrementally improved targeted drug candidates.

In June 2020, the European Medicines Agency (EMA) granted us Small and Medium-Sized Enterprise (SME) status by the EMA’s Micro, Small and Medium-sized Enterprise office.

We are also eligible to obtain EMA certification of quality and manufacturing data prior to review of clinical data.

A description of our PDC product candidates follows:

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Fatalities due to infection have occurred in patient treated with iopofosine.

The CLOVER-WaM pivotal Phase 2B study is enrolling WM patients that have failed or had a suboptimal response to a BTKi therapy after receiving first line standard of care.

The CLOVER-1 Phase 2 study met the primary efficacy endpoints from the Part A dose-finding portion, conducted in r/r B-cell malignancies, and is now enrolling an MM expansion cohort (Phase 2B).

The Phase 2B study will evaluate highly refractory MM patients including triple, quad and penta class refractory patients.

The CLOVER-WaM pivotal Phase 2b study is enrolling WM patients that have received two previous lines of therapy including those that failed or had a suboptimal response to a BTKi therapy.

The CLOVER-1 Phase 2 study met the primary efficacy endpoints from the Part A dose-finding portion, conducted in r/r B-cell malignancies, and is now enrolling an MM and CNSL expansion cohort (Phase 2b).

The Phase 2b study will evaluate highly refractory MM patients including triple, quad and penta class refractory patients including post-BCMA immunotherapy patients and r/r CNSL patients.

The initial Investigational New Drug (IND) application was accepted by the FDA in March 2014 with multiple INDs submitted since that time.

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Initiated in March 2017, the primary goal of the Phase 2a study was to assess the compound’s efficacy in a broad range of hematologic cancers.

The CLOVER-2 Phase 1 pediatric study is being conducted internationally at seven leading pediatric cancer centers.

The study is an open-label, sequential-group, dose-escalation study to evaluate the safety and tolerability of iopofosine in children and adolescents with relapsed or refractory cancers, including malignant brain tumors, neuroblastoma, sarcomas, and lymphomas (including Hodgkin’s lymphoma).

The FDA previously accepted our IND application for a Phase 1 open-label, dose escalating study to evaluate the safety and tolerability of a single intravenous administration of iopofosine in up to 30 children and adolescents with cancers including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors.

This study was initiated during the first quarter of 2019.

The CLOVER-2 Phase 1a pediatric study was conducted internationally at seven leading pediatric cancer centers.

The study was an open-label, sequential-group, dose-escalation study to evaluate the safety and tolerability of iopofosine in children and adolescents with relapsed or refractory cancers, including malignant brain tumors, neuroblastoma, sarcomas, and lymphomas (including Hodgkin’s lymphoma).

The maximum tolerated dose was determined to be greater than 60mCi/m 2 administered as a fractionated dose.

CLOVER-2 Phase 1b study is an open-label, international dose finding study evaluating iopofosine in r/r pediatric patients with high grade gliomas.

These cancer types were selected for clinical, regulatory and commercial rationales, including the radiosensitive nature and continued unmet medical need in the r/r setting, and the rare disease determinations made by the FDA based upon the current definition within the Orphan Drug Act.

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Patients with r/r Waldenstrom’s Macroglobulinemia

In January 2021, we announced that a Type C guidance meeting with the FDA was conducted in September 2020.

In January 2021, we announced that we participated in a Type C guidance meeting with the FDA in September 2020.

The results of that guidance meeting provided Cellectar with an agreed upon path for conducting the CLOVER-WaM study;

a single arm, pivotal study in WM patients that have received standard of care first line therapy and either failed or had a suboptimal response to BTKi therapy.

We believe this design is in alignment with the feedback received from the FDA during the guidance meeting held in September 2020.

The FDA accepted with the dose to be tested, our proposal for a safety and futility assessment to be conducted on the first 10 patients, the endpoint to be assessed, the statistical analysis plan and study size of 50 patients.

Based upon this agreement the pivotal study was initiated.

a single arm, pivotal study in WM patients that have received and relapsed or were refractory to two prior lines of therapy including failed or had a suboptimal response to BTKi therapy.

WM is a rare, indolent and incurable form of non-Hodgkin’s lymphoma (NHL) that is composed of a patient population in need of new and better treatment options.

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The primary endpoint of the trial is major response rate (MRR) as defined as a partial response (a minimum of a 50% reduction in IgM) or better in patients that receive a minimum total body dose (TBD) of 60 mCi with secondary endpoints of treatment free survival (treatment free remission), duration of response and progression free survival.

An independent data monitoring committee (IDMC) will perform an interim safety and futility evaluation on the first 10 patients enrolled.

If three of the 10 patients experience a Clinically Significant Toxicity (CST) then the dose will be reduced to 12.5 mCi/m 2 .

The assessment will occur patient by patient and will conclude after the tenth patient is evaluated;

there is no planned study stoppage.

The trial has been initiated at select US and international cancer centers and sites.

An independent data monitoring committee (IDMC) performed an interim safety and futility evaluation on the first 10 patients enrolled.

If three of the 10 patients experience a Clinically Significant Toxicity (CST) then the dose would have been reduced to 12.5 mCi/m 2 .

We believe this design is aligned with the feedback received from the FDA during the guidance meeting held in September 2020.

The FDA accepted the dose to be tested, our proposal for a safety and futility assessment to be conducted on the first 10 patients, the endpoint to be assessed, the statistical analysis plan and study size of 50 patients.

Based upon this agreement the pivotal study was initiated.

The interim futility and safety assessment occurred in 2022 and iDMC determined the study exceeded the futility threshold and that the CST threshold was not met therefore the study should continue to enroll with no change to the dosing regimen.

Phase 2 Study in Select B-Cell Malignancies

The Phase 2 CLOVER-1 study is an open-label study designed to determine the efficacy and safety of CLR 131 in select B-cell malignancies (multiple myeloma (MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom’s macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), DLBCL, and central nervous system lymphoma (CNSL) who have been previously treated with standard therapy for their underlying malignancy.

As of March 2022, the study arms for CLL/SLL, LPL/WM, MZL, MCL, and DLBCL are closed.

The Phase 2 CLOVER-1 study was an open-label study designed to determine the efficacy and safety of CLR 131 in select B-cell malignancies (multiple myeloma (MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom’s macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), DLBCL, and central nervous system lymphoma (CNSL) who have been previously treated with standard therapy for their underlying malignancy.

As of March 2022, the study arms for CLL/SLL, LPL/WM, MZL, MCL, and DLBCL were closed.

Dosing of patients varied by disease state cohort and was measured in terms of TBD.

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These niche hematologic malignancies include CLL, SLL, MZL, LPL/WM and DLBCL.

The study is being conducted in approximately 10 U.S.

The study was conducted in approximately 10 U.S.

cancer centers in patients with orphan-designated relapse or refractory hematologic cancers.

The planned study enrollment was up to 80 patients.

The study’s primary endpoint is clinical benefit response (CBR), with secondary endpoints of overall response rate (ORR), progression free survival (PFS,), time to next treatment (TtNT), median Overall Survival (mOS), duration of response (DOR) and other markers of efficacy following patients receiving one of three TBDs of iopofosine (<50mCi, ~50mCi and >60mCi), with the option for a second cycle approximately 75-180 days later.

The study’s primary endpoint was clinical benefit response (CBR), with secondary endpoints of overall response rate (ORR), progression free survival (PFS,), time to next treatment (TtNT), median Overall Survival (mOS), duration of response (DOR) and other markers of efficacy following patients receiving one of three TBDs of iopofosine (<50mCi, ~50mCi and >60mCi), with the option for a second cycle approximately 75-180 days later.

Dosages were provided either as a single bolus or fractionated (the assigned dose level split into two doses) given day 1 and day 15.

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Triple class refractory is defined as patients that are refractory to immunomodulatory, proteasome inhibitors and anti-CD38 antibody drug classes.

The 40% ORR (6/15 patients) represents triple class refractory patients enrolled in Part A of Cellectar’s CLOVER-1 study and additional patients enrolled in Part B from March through May 2020 and received > 60mCi TBD (25 mCi/m2 single bolus, 31.25 mCi/m2 fractionated, 37.5 mCi/m2 fractionated, or two cycles

of mCi/m2 fractionated) either as a bolus dose or fractionated.

Patients with MM received 40 mg of dexamethasone concurrently beginning within 24 hours of the first CLR 131 infusion.

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Based on study results to date, patients continue to tolerate iopofosine well, with the most common and almost exclusive treatment-emergent adverse events are cytopenias, such as thrombocytopenia, neutropenia, and anemia.

In December 2021, we presented data from 11 MM patients from our ongoing Phase 2 CLOVER-1 study in a poster at the American Society of Hematology (ASH) Annual Meeting and Exposition.

The MM patients were at least triple class refractory (defined as refractory to an immunomodulatory agent, proteasome inhibitor and monoclonal antibody) with data current as of the end of May 2021.

Patients had a median of greater than 7 prior therapies with 50% classified as high risk.

Initial results in these patients showed an ORR of 45.5%, a CBR of 72.7% and a disease control rate (DCR) of 100%.

Median PFS was 3.4 months.

In a subset of 5 quad/penta drug refractory patients, efficacy increased, demonstrating an ORR of 80% and CBR of 100% in this highly treatment refractory group.

The most commonly observed treatment emergent adverse events were cytopenias that included Grade 3 or 4 thrombocytopenia (62.5%), anemia (62.5%), neutropenia (62.5%) and decreased white blood cell count (50%).

Treatment emergent adverse events were mostly limited to bone marrow suppression in line with prior observations.

No patients experienced a treatment emergent adverse event of neuropathy, arrhythmia, cardiovascular event, bleeding, ocular toxicities, renal function, alterations in liver enzymes, or infusion-site reactions or adverse events.

We continue to enrich the r/r MM patient cohort with patients that are even more refractory.

Specifically enrolling patients that are quad-class refractory (triple class plus refractory to any of the recent approved product classes) and have relapsed post-BCMA immunotherapy.

We reported in the Blood Cancer Journal in August 2022, that iopofosine demonstrated a 50% ORR in patients receiving > 60mCi total administered dose (3/6 patients).

Patients with r/r non-Hodgkin’s lymphoma Cohort

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Phase 1 Study in Patients with r/r Multiple Myeloma

In February 2020, we announced the successful completion of our Phase 1 dose escalation study.

Data from the study indicate that iopofosine was tolerated up to a TBD of approximately 95mCi in r/r MM.

The Phase 1 multicenter, open-label, dose-escalation study was designed to evaluate the safety and tolerability of iopofosine administered in an up to 30-minute I.V.

infusion, either as a single bolus dose or as fractionated doses.

The r/r MM patients in this study received single cycle doses ranging from approximately 20mCi to 95mCi TBD.

An IDMC assessed the safety of all doses used with patients and deemed them to be safe and tolerated.

In February 2020, final results from a multicenter, Phase 1 dose escalation clinical trial of iopofosine in r/r MM were presented.

The trial was designed to evaluate the safety and potential initial efficacy of iopofosine administered in an up to 30-minute I.V.

infusion either as a single bolus dose or as a fractionated dose in heavily pretreated MM patients.

The study enrolled a total of 26 evaluable patients at three trial sites.

For the trial, which used a modified 3 + 3 dose escalation design, 15 evaluable patients were dosed in single bolus doses from 12.5mCi/m2 up to 31.25mCi/m2 (TBD 20.35-59.17 mCi) and 11 evaluable patients were dosed in fractionated dosing cohorts of 31.25mCi/m2 to 40mCi/m2 (TBD 54.915-89.107 mCi).

An iDMC did not identify dose-limiting toxicities in any cohort.

Of the 26 evaluable patients in the trial, a partial response was observed in 4 of 26 patients (15.4)% and stable disease or minimal response in 22 of 26 patients (84.6)%, for a disease control rate of 100%.

A significant decrease in M-protein and FLC was also observed.

Iopofosine in combination with dexamethasone was under investigation in adult patients with r/r MM.

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Secondary objectives included the evaluation of therapeutic activity by assessing surrogate efficacy markers, which include M protein, free light chain (FLC), PFS and OS.

All patients were heavily pretreated with an average of five

prior lines of therapy.

All patients were heavily pretreated with an average of five prior lines of therapy.

An IDMC assessed the safety of iopofosine up to its planned maximum single, bolus dose of 31.25 mCi/m 2 or a TBD of ~63 mCi.

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Following treatment with iopofosine, approximately 91% of patients experience a reduction in tumor marker with approximately 73% experiencing greater than 37% reduction.

In December 2021, we presented data from 11 MM patients from our ongoing Phase 2 CLOVER-1 study in a poster at the American Society of Hematology (ASH) Annual Meeting and Exposition.

The MM patients were at least triple class refractory (defined as refractory to an immunomodulatory agent, proteasome inhibitor and monoclonal antibody) with data current as of the end of May 2021.

Patients had a median of greater than 7 prior therapies with 50% classified as high risk.

Initial results in these patients showed an ORR of 45.5%, a CBR of 72.7% and a disease control rate (DCR) of 100%.

Median PFS was 3.4 months.

In a subset of 5 quad/penta drug refractory patients, efficacy increased, demonstrating an ORR of 80% and CBR of 100% in this highly treatment refractory group.

The most commonly observed treatment emergent adverse events were cytopenias that included Grade 3 or 4 thrombocytopenia (62.5)%, anemia (62.5)%, neutropenia (62.5)% and decreased white blood cell count (50)%.

Treatment emergent adverse events were mostly limited to bone marrow suppression in line with prior observations.

No patients experienced a treatment emergent adverse event of neuropathy, arrythmia, cardiovascular event, bleeding, ocular toxicities, renal function, alterations in liver enzymes, or infusion-site reactions or adverse events.

Phase 1 Study in r/r Pediatric Patients with select Solid tumors, Lymphomas and Malignant Brain Tumors

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Secondary objectives of the study are to identify the recommended efficacious dose of iopofosine and to determine preliminary antitumor activity (treatment response) of iopofosine in children and adolescents.

In August 2020, based on data on four dose levels from 15mCi/m 2 up to 60mCi/m2, an DMC permitted the beginning of the evaluation of the next higher dose cohort, at 75mCi/m2.

In August 2020, based on data on four dose levels from 15mCi/m 2 up to 60mCi/m2, the iDMC permitted the beginning of the evaluation of the next higher dose cohort, at 75mCi/m2.

The iDMC advised, based upon the initial data, to enrich the 60 mCi/m2 dose level for patients over the age of 10 with HGG and Ewing sarcoma.

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There were no serious adverse events occurring in more than 2 subjects.

The Part A portion of this Phase 1 study has concluded and part B is initiating to determine the appropriate dosing regimen in pediatric patients with r/r HGG.

In 2022, the NCI award Cellectar a $1.9M SBIR Phase 2 grant to explore iopofosine in pediatric HGG.

In 2018, the FDA granted ODD and RPDD for iopofosine for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma.

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however, this approach can cause severe injury to normal tissue structures, significant adverse events and diminished quality of life.

Part B of the study will further assess the safety and potential benefits of iopofosine in combination with EBRT in a cohort of up to 24 patients.

Part B of the study was to assess the safety and potential benefits of iopofosine in combination with EBRT in a cohort of up to 24 patients.

This portion of the study has fully enrolled.

Adverse events occurring in at least 25% of subjects were fatigue (46%) and cytopenias, specifically, thrombocytopenia (69%), anemia (77%), neutropenia (54%), leukopenia (69%), and lymphopenia (62%).

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Currently, the program is in early preclinical development and if we elect to progress any molecules further, we will select preferred candidates.

● CLR 2000 Series is a collaborative PDC program with Avicenna Oncology, or Avicenna, that we entered into in July 2017.

Avicenna is a developer of antibody drug conjugates (ADCs).

The objective of the research collaboration is to design and develop a series of PDCs utilizing Avicenna’s proprietary cytotoxic payload.

Although Avicenna is a developer of ADCs,

this collaboration was sought as a means to overcome many of the challenges associated with ADCs, including those associated with the targeting of specific cell surface epitopes.

The CLR 2000 Series has demonstrated improved safety, efficacy and tissue distribution with the cytotoxic payload in animal models.

A candidate molecule and a back-up have been selected for further advancement at a future time.

● CLR 12120 Series is an alpha emitting radio-conjugate program.

A collaboration with Orano Med was initiated to validate the potential of this class of PDC radio-conjugates and for the potential development of novel PDCs utilizing Orano Med’s unique alpha emitter, lead 212 conjugated to our phospholipid ether.The companies evaluated the new PDCs in three oncology indications.

The companies evaluated the new PDCs in three oncology indications.

The collaboration successfully met its endpoints with the in vivo animal data demonstrating that the PDC combined with an alpha emitting radioisotope resulted in significant reduction in tumor volumes in all animal models tested.

● Expanded ongoing collaboration with biotechnology company IntoCell Inc., combining their novel linker chemistry with our validated targeting platform to create novel next generation phospholipid drug conjugate therapeutics.

This series is now focused on utilizing the PDC in combination with actinium and astatine.

● The collaboration with IntoCell Inc., successfully met its agreed upon endpoint.

The collaboration provided significant data which has led Cellectar to select a series of highly potent cytotoxic small molecule payloads for further development.

● Co-development and commercialization collaboration with LegoChemBio, a clinical stage biotechnology company to utilize their proprietary drug conjugate linker-toxin platform to further enhance our portfolio of next generation PDC therapeutics.

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Data suggests that lipid rafts serve as portals of entry for PDCs such as iopofosine and our multiple series of drug conjugates.

The marked selectivity of our compounds for cancer cells versus non-cancer cells likely results

from cancer cells maintenance of an overabundance of lipid rafts and the stabilization of these microdomains within the plasma membrane as compared to normal cells.

The marked selectivity of our compounds for cancer cells versus non-cancer cells likely results from cancer cells maintenance of an overabundance of lipid rafts and the stabilization of these microdomains within the plasma membrane as compared to normal cells.

Following cell entry via lipid rafts, iopofosine is transported into the cytoplasm, where it traffics along the Golgi apparatus and is distributed to various peri-nuclear organelles (including mitochondria and the endoplasmic reticulum).

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Products in Development

Iopofosine is a small-molecule PDC designed to provide targeted delivery of iodine-131 (radioisotope) directly to cancer cells, while limiting exposure to healthy cells unlike many traditional on-market treatment options.

Iopofosine is comprised of our proprietary PLE, 18-(p-[I-131]iodophenyl) octadacyl phosphocholine, acting as a cancer-targeting delivery and retention vehicle, covalently labeled with iodine-131, a cytotoxic (cell-killing) radioisotope with a half-life of eight days that is already in common use to treat thyroid, pediatric tumors and other cancer types including NHL.

Iopofosine is a small molecule, radioconjugate, composed of our proprietary PLE, 18-(p-[I-131]iodophenyl) octadacyl phosphocholine, acting as a cancer-targeting delivery and retention vehicle, covalently labeled with iodine-131, a cytotoxic (cell-killing) radioisotope with a half-life of eight days that is already in common use to treat thyroid, pediatric tumors and other cancer types including NHL.

Iopofosine binds to the cell surface of cancer cells and is delivered into the cytoplasm of the cancer cell.

It is this “intracellular radiation” mechanism of cancer cell killing, coupled with delivery to a wide range of malignant tumor types that we believe provides iopofosine with anti-cancer activity and a unique product profile.

Selective uptake and retention have been demonstrated in cancer stem cells compared with normal cells, offering the prospect of longer lasting anti-cancer activity.

Cellectar conducted early dosimetry studies to determine whole body uptake and distribution.

The primary objective of the multicenter Phase 1b dose-escalation study in patients with a range of advanced solid tumors was to define the MTD of iopofosine.

In addition to determining the MTD, the Phase 1b study was intended to evaluate overall tumor response (using standard RESIST 1.1 criteria) and safety.

In September 2012, we announced that we had successfully completed the second cohort in this Phase 1b dose-escalation study.

Dose escalation in four cohorts subsequently occurred with refractory cancer patients receiving single doses of 25 mCi/m 2 , 31.25 mCi/m 2 or 37.5 mCi/m 2 .

Tumor treatment with radioactive isotopes has been used as a fundamental cancer therapeutic for decades.

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We believe our targeted delivery technology has the potential to achieve these goals.

Iopofosine has been shown in animal models to reliably and near-universally accumulate in cancer cells, including cancer stem cells.

In view of preclinical data suggesting selective uptake and retention of iopofosine in a wide range of solid tumors and in cancer stem cells, its single-agent activity in animal models and its non-specific mechanism of cancer-killing (radiation), along with an understanding of classical oncology drug development our initial plan was to develop iopofosine as a monotherapy for cancer indications with significant unmet medical need.

Iopofosine’s unique benefits such as a novel mechanism of action, ease of administration, and positive benefit/risk profile offered potential treatment benefits for a variety of high unmet cancer populations.

While a number of cancer indications were evaluated as the initial target treatment, MM was selected principally because, like many hematologic malignancies, is known to be highly radiosensitive and remains an incurable hematologic disease with significant unmet medical need in the relapse or refractory clinical setting.

Additionally, MM is designated as an orphan disease and drugs granted an ODD are provided regulatory and marketing exclusivity benefits.

The IND application for MM was accepted by the FDA in September 2014.

In December 2014, the FDA granted ODD for iopofosine for the treatment of MM.

We initiated our Phase 1 Study of iopofosine for the treatment of r/r MM in April 2015.

The Phase 1 study was a multicenter, open-label, dose-escalation study designed to evaluate the safety and tolerability of iopofosine administered as a 15-20-minute IV infusion, either as a single bolus dose or as two fractionated doses, in patients with R/R MM.

The safety of doses used for all cohorts dosed was as assessed by an IDMC.

The study was successfully completed in February 2020 .

In February 2020, final results from a multicenter, Phase 1 clinical trial of iopofosine in r/r MM were presented.

The trial was designed to evaluate the safety and potential initial efficacy of iopofosine in heavily pretreated MM patients and enrolled a total of 26 evaluable patients at three trial sites.

An IDMC did not identify dose-limiting toxicities in any cohort.

A significant decrease in M-protein and FLC was also observed, which may suggest targeting of the tumor.

The Phase 2a study (CLOVER-1) of iopofosine was initiated in July 2017 and conducted in approximately 10 leading cancer centers in the U.S.

for patients with relapsed or refractory B-cell hematologic cancers.

The hematologic cancers studied in the trial included MM, LPL/WM, CLL/SLL, MZL, MCL, and DLBCL.

In July 2018, we announced that data collected after a single 25mCi/m 2 IV administration of iopofosine, in patients with r/r aggressive DLBCL.

These interim data show a 33% ORR and a 50% CBR.

In addition, the observed responses to date show overall tumor reduction ranged from 60% to greater than 90%.

As a result of these favorable outcomes, we have expanded this cohort to include up to 30 additional patients.

We also announced that a patient in the LPL arm with advanced WM showed a 94% reduction in tumor burden and complete resolution in four of five targeted masses after two doses of iopofosine separated by 123 days.

The FDA has granted ODD’s and RPDDs for iopofosine for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma.

Should any of these indications reach approval, the RPDD may enable us to receive a priority review voucher.

Priority review vouchers can be used by the sponsor to receive Priority Review for a future NDA or BLA submission, which would reduce the statutory FDA’s review target from 10 months from filing to six months.

Currently, these vouchers can also be transferred or sold to another entity.

Iopofosine has been shown in animal models and various clinical studies to reliably and near-universally accumulate in cancer cells, including cancer stem cells.

This strategy has allowed us to take a multi-indication approach in the development and potential commercialization of iopofosine.

To date, the Company has focused on rare cancers with significant unmet need including Waldenstrom’s macroglobulinemia, multiple myeloma, sarcomas, high grade glioma, etc.

Market Overview

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in 2022 and approximately 609,360 cancer deaths in the U.S.

The global market for cancer drugs reached $135 billion in annual sales (2020), and with a compound annual growth rate (CAGR) of 7.5% could reach $275 billion by 2030, according to a report dated November 2021 by Allied Market Research.

The global market for cancer drugs reached $148 billion in annual sales (2020), and with a compound annual growth rate (CAGR) of 7.7% could reach $288 billion by 2030, according to a report dated August 2022 by Straits Research.

This growth will be driven by emerging targeted therapies, which are expected to change the cancer treatment landscape (Cowen Report 2020), and an increased use of cancer drug combination regimens.

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WM is a rare and incurable disease defined by specific genotypic subtypes that defines patient responses and long-term outcomes.

The annual incidence is 11,000 with prevalence of approximately 110,000 patients globally.

annual incidence is 3,000 with prevalence of approximately 110,000 patients globally.

WM is a lymphoma, or cancer of the lymphatic system.

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According to the National Cancer Institute SEER database, multiple myeloma is the second most common hematologic cancer with a U.S.

incidence rate and a relapse or refractory patient population of 10,000 to 15,000.

In 2020, Global Data Research Group estimated the MM dollar market size to be over $20B in 2021 and is forecasted to increase to nearly $28B in 2027.

incidence rate of 32,270 and a relapse or refractory patient population of 43,727.

In 2022, Datamonitor Healthcare estimated the MM dollar market size to be over $23B in 2023 and is forecasted to increase to nearly $47B in 2031.

The increase in drug sales over this period will be mainly driven by the increasing incidence of MM with the U.S.

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It is believed the largest growth will occur in patients receiving at least three lines of treatment due to the expanding elderly population, increases in treatment population and increasing rates of survival from earlier lines of treatment.

According to data

obtained from Decision Resource Group, over 40% of patients in later lines of therapy, while eligible, refuse treatment due to higher treatment failure, severity of adverse events and difficulty of treatment dosing regimen.

According to data obtained from Decision Resource Group, over 40% of patients in later lines of therapy, while eligible, refuse treatment due to higher treatment failure, severity of adverse events and difficulty of treatment dosing regimen.

The average response rates for patients receiving their fourth and fifth-line treatment are 15% and 8% response rates, respectively.

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Based on the iopofosine Phase 1 and Phase 2 product profile demonstrated in fifth-line patients to date, we believe iopofosine may meet the unmet medical need in the heavily pre-treated patient population described above.

B-Cell Lymphoma

B-cell lymphoma represents cancers of the lymphatic system.

B-Cell Non-Hodgkin’s Lymphoma

B-cell Non-Hodgkin’s Lymphoma (BCNHL) represents cancers of the lymphatic system.

The lymphoma may be indolent or aggressive and circulate in the blood or form tumors in lymph nodes.

According to the WHO Global Cancer Observatory database, the estimated 2020 US incidence of B-cell lymphoma was 66,289 cases.

According to the American Cancer Society, the estimated 2023 US incidence of BCNHL was 68,468 cases.

Nine types of B-cell lymphomas include CLL, SLL, MCL, MZL, and the most common lymphoma, DLBCL.

According to a report dated June 2019 by Global Data Research Group, the B-cell lymphoma market was valued at $7.6 billion for 2022, with a forecasted increase to $11.7 billion in 2032 at a CAGR of 4.9%.

According to a report dated June 2019 by Global Data Research Group, the BCNHL market was valued at $7.2 billion for 2022, with a forecasted increase to $11.7 billion in 2032 at a CAGR of 4.9%.

We believe there is a significant unmet medical need in B-cell lymphoma due to continued high mortality and poor response rates remain in second and third- line treatments compounded by the limited durability of responses.

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Neuroblastoma

Neuroblastoma, a neoplasm of the sympathetic nervous system, is the most common extracranial solid tumor of childhood, accounting for approximately 7.8% of childhood cancers in the U.S.

Neuroblastoma, a neoplasm of the sympathetic nervous system, is the most common extracranial solid tumor of childhood, accounting for approximately 7-10% of childhood cancers and 50% of infant cancers, in the U.S.

The NCI states the incidence is about 10.54 cases per 1 million per year in children younger than 15 years and 90% are younger than 5 years at diagnosis.

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Clinical consequences include abdominal distension, proptosis, bone pain, pancytopenia, fever and paralysis.

Although the prognosis is favorable in children under one year of age with an 86 to 95% 5-year survival, in children aged one to 14 years the 5-year survival ranges from 34 to 68%.

Although treatment rates have improved within the clinical paradigm, half of children with neuroblastoma still relapse or fail to respond to upfront therapy.

Survival for those with relapsed or refractory neuroblastoma currently reports as a 4-year overall survival rate of 20%.

High Grade Glioma

High Grade Glioma (HGG) is a fast-growing tumor of glial cells in the brain or spinal cord.

The WHO classifies these as Grade 3 or 4 based on the growth rate, and these tumors are often not curable.

Approximately 10-20% of pediatric tumors are HGG, amounting to a global incidence of approximately 33,000 cases.

Available treatment options are limited to surgery, radiation therapy, and aggressive chemotherapeutic combinations.

Prognosis continues to improve with development of targeted therapies, but the 5-year overall survival rate is still less than 20%.

Sarcomas represent a heterogeneous disease group.

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We have also demonstrated 60-month stability for the drug substance in desiccated and refrigerated forms at small scale and are replicating this at large scale.

The Centre for Probe Development and Commercialization (CPDC), a validated Current Good Manufacturing Practices (cGMPs) manufacturing organization specializing in radiopharmaceuticals, is our exclusive source to supply drug product for our ongoing research and clinical studies, including our Phase 1 and Phase 2 studies of iopofosine.

We believe that CPDC and our other third-party manufacturers have the ability to supply large scale clinical and commercial scale material.

AtomVie (formerly known as The Centre for Probe Development and Commercialization (CPDC)), a validated Current Good Manufacturing Practices (cGMPs) manufacturing organization specializing in radiopharmaceuticals, is our primary source to supply drug product for our ongoing research and clinical studies, including our Phase 1 and Phase 2 studies of iopofosine.

We believe that AtomVie and our other third-party manufacturers have the ability to supply large scale clinical and commercial scale material.

Sales and Marketing

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These patent applications further protect composition of matter and method of use for PDCs developed with our proprietary phospholipid-ether delivery vehicle conjugated with any existing or future cytotoxic agents, including chemotherapeutics for targeted delivery to cancer cells and cancer stem cells.

Additional cytotoxic PDC compounds are covered by pending patent applications directed to the composition of matter and method of use for cancer therapy provide intellectual property protection in the U.S.

and up to 157 additional countries.

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This approach includes numerous patents, patent applications and regulatory filings to provide maximum market exclusivity.

Our patent portfolio for iopofosine includes all the typical filings as well as unique methods of use, methods of manufacturing, use in combinations, use to treat cancer stem cells, novel formulations, etc.

Our patent portfolio for iopofosine includes all the typical filings as well as unique methods of use, methods of synthesis, use in combinations, use to treat cancer stem cells, novel formulations, etc.

In addition to our patents, we were granted ODD for iopofosine by the FDA for the treatment of MM in December 2014 and for WM in January 2020.

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We initiated a Phase 1 study in 2019.

We expect to continue to file patent applications and acquire licenses to other patents covering methods of use, composition of matter, formulation, method of manufacture and other patentable claims related to iopofosine and new PDCs.

We expect to continue to file patent applications and acquire licenses to other patents covering methods of use, composition of matter, formulation, method of synthesis and other patentable claims related to iopofosine and new PDCs.

These patent applications will be filed in key commercial markets worldwide.

The issued patents will generally expire between 2025 and 2035, unless extended, most likely under clinical development extensions.

In addition to the above noted patents/applications directed to iopofosine and our PDC pipeline portfolio, we own other patents/applications directed to different forms of phospholipid ethers, methods of use and methods of manufacturing of phospholipid ethers.

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In August 2018, we entered into a collaboration with Orano Med for the development of novel PDCs utilizing Orano Med’s alpha emitter lead-212 conjugated to our phospholipid ether;

the companies intend to evaluate the new PDCs in up to three oncology indications.

the companies evaluated the new PDCs in up to three oncology indications.

The collaboration successfully met its endpoints.

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However due to the limited half-life and associated logistical challenges associated with lead-212, Cellectar has elected to advance with an alternative alpha emitting radioisotope.

In July 2017, we entered into an arrangement with Avicenna Oncology GmbH (Avicenna).

Under this arrangement, Avicenna will provide us a selection of its proprietary toxins.

We will use our proprietary conjugation capabilities to proceed with the conjugation in order to obtain PDCs.

We will process various in vitro and in cellulo screening against such PDCs to develop new conjugates.

We granted Avicenna an exclusive option to acquire an exclusive license to our intellectual property with respect to each conjugate developed.

In the event the parties cannot reach agreement on the terms of a definitive agreement despite good faith negotiations, Avicenna’s exclusive option terminates as to such conjugate.

Avicenna also granted to us an exclusive option to acquire an exclusive license to its intellectual property with respect to the material provided.

In the event the parties do not reach agreement on the terms of a definitive agreement, our exclusive option terminates as to the material of Avicenna.

In July 2021, we expanded our ongoing collaboration with biotechnology company IntoCell Inc., combining their novel linker chemistry with our validated targeting platform to create novel next generation phospholipid drug conjugate therapeutics.

In July 2021, we entered into a co-development and commercialization collaboration with LegoChemBio, a clinical stage biotechnology company to utilize their proprietary drug conjugate linker-toxin platform to further enhance our portfolio of next generation PDC therapeutics.

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Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions.

not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

On the basis of the FDA’s evaluation of the NDA and accompanying information, including the results of the inspection of the manufacturing facilities, the FDA may issue an approval letter or a complete response letter.

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The FDA determines, on a case-by-case basis, whether the proposed product represents a significant improvement when compared with other available therapies.

Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or

substantial reduction of a treatment limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation.

Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation.

RPDD by the FDA enables priority review voucher (PRV) eligibility upon U.S.

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The FDA also enforces the Drug Supply Chain Security Act, or DSCSA, which regulates the distribution and tracing of prescription drugs and prescription drug samples at the federal level, sets minimum standards for the regulation of drug distributors by the states, and imposes requirements to track and trace drug products, ensure accountability in distribution and to identify and remove counterfeit and other illegitimate products from the market.

In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies and are subject to periodic unannounced inspections by the FDA and

these state agencies for compliance with cGMP requirements.

Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented.

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Unlike five-year NCE exclusivity, an award of three-year exclusivity does not block the FDA from accepting ANDAs or 505(b)(2) NDAs seeking approval for generic versions of the drug as of the date of approval of the original drug product;

it does, however, block the

FDA from approving ANDAs or 505(b)(2) NDAs during the period of exclusivity.

it does, however, block the FDA from approving ANDAs or 505(b)(2) NDAs during the period of exclusivity.

The FDA typically makes decisions about awards of data exclusivity shortly before a product is approved.

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FCA liability is potentially significant in the healthcare industry because the statute provides for treble damages and significant mandatory penalties per false or fraudulent claim or statement for violations.

Such per-claim penalties are currently set at $11,803 to $23,607 per false claim or statement for penalties assessed after December 13, 2021, with respect to violations occurring after November 2, 2015.

Such per-claim penalties are currently set at $13,508 to $27,018 per false claim or statement for penalties assessed after January 30, 2023, with respect to violations occurring after November 2, 2015.

Criminal penalties, including imprisonment and criminal fines, are also possible for making or presenting a false, fictitious or fraudulent claim to the federal government;

the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program,

including any third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statements or representations, or making false statements relating to healthcare benefits, items or services.

● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program, including any third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statements or representations, or making false statements relating to healthcare benefits, items or services.

Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation;

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HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions;

the federal Physician Payments Sunshine Act, implemented as the Open Payments Program, which requires certain manufacturers of drugs, devices, biologics and medical supplies, among others, to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the U.S.

Department of Health and Human Services (HHS), information related to payments and other transfers of value made by that entity to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), teaching hospitals, physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants and certified nurse midwives, as well as ownership and investment interests held by physicians and their immediate family members;

● the federal Physician Payments Sunshine Act, implemented as the Open Payments Program, which requires certain manufacturers of drugs, devices, biologics and medical supplies, among others, to report annually to the CMS, information related to payments and other transfers of value made by that entity to U.S.

licensed physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), teaching hospitals, physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants, certified nurse midwives, and U.S.

teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;

● analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers.

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In addition, under current U.S.

law, there are

restrictions on the export of products not approved by the FDA, depending on the country involved and the status of the product in that country.

law, there are restrictions on the export of products not approved by the FDA, depending on the country involved and the status of the product in that country.

Reimbursement and Pricing Controls

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However, “orphan drugs” i.e., those designated under section 526 of the federal Food, Drug, and Cosmetic Act (FDCA) are exempted from the ceiling price requirements for these eligible entities added by the Affordable Care Act (except for certain children’s hospitals).

The 340B ceiling price is calculated using a statutory formula, which is based on the average manufacturer price and rebate amount for the covered outpatient drug as calculated under the MDRP, and in general, products subject to the MDR P are also subject to the 340B ceiling price calculation and discount requirement.

The 340B ceiling price is calculated using a statutory formula, which is based on the average manufacturer price and rebate amount for the covered outpatient drug as calculated under the MDRP, and in general, products subject to the MDRP are also subject to the 340B ceiling price calculation and discount requirement.

In addition, after multiple delays, the final rule implementing civil monetary penalties against manufacturers for instances of overcharging 340B covered entities became effective on January 1, 2019.

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Federal law requires that for a company to be eligible to have its products paid for with federal funds under the Medicaid and Medicare Part B programs as well as to be purchased by certain federal agencies and grantees, it also must participate in the Department of Veterans Affairs (VA) Federal Supply Schedule (FSS) pricing program.

To participate, we will be required to enter into an FSS contract and other agreements with the VA for our products, which may qualify as “covered drugs.” Under these agreements, we would need to make our products available to the “Big Four” federal agencies—the VA, the Department of Defense (DoD), the Public Health Service (including the Indian Health Service), and the Coast Guard—at pricing that is capped pursuant to a

statutory federal ceiling price, or FCP, formula set forth in Section 603 of the Veterans Health Care Act of 1992 (VHCA).

The FCP is based on a weighted average non-federal average manufacturer price (Non-FAMP), which manufacturers are required to report on a quarterly and annual basis to the VA.

Pursuant to the VHCA, knowing provision of false information in connection with a Non-FAMP filing can subject a manufacturer to a penalty for each item of false information and could result in other potential liability as well, including liability under the False Claims Act.

Pursuant to the VHCA, the knowing provision of false information in connection with a Non-FAMP filing can subject a manufacturer to a penalty for each item of false information and could result in other potential liability as well, including liability under the False Claims Act.

FSS contracts are federal procurement contracts that include standard government terms and conditions, separate pricing for each product, and extensive disclosure and certification requirements.

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Significant uncertainty exists as to the pricing and reimbursement of products approved by the FDA and other government authorities.

For example, there have been several recent US Congressional inquiries and proposed federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs.

In the US, some of these proposals at the federal level have included directing Medicare to negotiate directly with manufacturers for the costliest drugs;

various Medicare Part D and Medicaid reforms;

price reporting transparency;

importation rulemaking;

an international pricing index proposal to require additional discounts to Medicare, as well as a proposal requiring manufacturers to pay a rebate to the federal government if the price of a Medicare Part B or Part D drug increases more than the rate of inflation.

There have been several recent US Congressional inquiries and proposed federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs.

For example, included in the Consolidated Appropriations Act of 2021 were several drug price reporting and transparency measures, such as a new requirement for certain Medicare plans to develop tools to display Medicare Part D prescription drug benefit information in real time and for group and health insurance issuers to report information on pharmacy benefit and drug costs to the Secretaries of the Departments of Health and Human Services, Labor and the Treasury.

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Effective January 1, 2024, manufacturers’ MDRP rebate liability will no longer be capped, potentially resulting in a manufacturer paying more in MDRP rebates than it receives on the sale of certain covered outpatient drugs.

On February 2, 2022, the Biden Administration signaled its continued commitment to the Cancer Moonshot initiative, which was initially launched in 2016.

In its announcement, the administration noted that its new goals under the initiative include addressing inequities in order to ensure broader access to cutting-edge cancer therapeutics and investing in a robust pipeline for new treatments.

Additionally, in August 2022, President Biden signed into law the Inflation Reduction Act of 2022, which implements substantial changes to the Medicare program, including drug pricing reforms and creation of new Medicare inflation rebates.

Namely, the IRA imposes inflation rebates on drug manufacturers for products reimbursed under Medicare Parts B and D if the prices of those products increase faster than inflation;

implements changes to the Medicare Part D benefit that, beginning in 2025, will cap beneficiary annual out-of-pocket spending at $2,000, while imposing new discount obligations for pharmaceutical manufacturers;

and beginning in 2026, establishes a “maximum fair price” for a fixed number of high expenditure pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with CMS.

On October 14, 2022 President Biden issued an Executive Order on Lowering Prescription Drug Costs for Americans, which instructed the Secretary of the Department of Health and Human Services to consider whether to select for testing by the CMS Innovation Center new health care payment and delivery models that would lower drug costs and promote access to innovative drug therapies for beneficiaries enrolled in the Medicare and Medicaid programs.

Most recently, on February 14, 2023, the Department of Health and Human Services issued a report in response to the October 14, 2022 Executive Order, which, among other things, selects three potential drug affordability and accessibility models to be tested by the CMS Innovation Center.

Specifically, the report addresses:

(1) a model that would allow Part D Sponsors to establish a “high-value drug list” setting the maximum co-payment amount for certain common generic drugs at $2;

(2) a Medicaid-focused model that would establish a partnership between CMS, manufacturers, and state Medicaid agencies that would result in multi-state outcomes-based agreements or certain cell and gene therapy drugs;

and (3) a model that would adjust Medicare Part B payment amounts for Accelerated Approval Program drugs to advance the developments of novel treatments.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing, cost disclosure and transparency measures, and, in some cases, to encourage importation from other countries and bulk purchasing.

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Employees and Human Capital

As of December 31, 2021, we had twelve employees, all of whom are full-time employees.

Of these twelve employees, six employees were engaged in research and development.

As of December 31, 2022, we had fifteen employees, all of whom are full-time employees.

Of these fifteen employees, nine employees were engaged in research and development.

None of our employees is subject to a collective bargaining agreement or represented by a trade or labor union.

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District Court for the Western District of Wisconsin.

The Company is alleging, among other claims, that Dr.

The Company alleged, among other claims, that Dr.

Weichert and Dr.

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Although the disputed intellectual property does not directly affect the clinical studies of iopofosine or other compounds in the Company’s clinical pipeline, the disputed intellectual property may potentially enhance future areas of research, development, and commercialization.

The Company is seeking monetary damages, injunctive relief, and reasonable attorneys’ fees and expenses in conjunction with this lawsuit.

The Company was seeking monetary damages, injunctive relief, and reasonable attorneys’ fees and expenses in conjunction with the lawsuit.

In November 2022, the Company announced that the Company, the Wisconsin Alumni Research Foundation (WARF), and Dr.

Weichert and Dr.

Pinchuk have resolved the lawsuit.

All claims against Drs.

Weichert and Pinchuk have been voluntarily dismissed, and the Company has secured an irrevocable, non-exclusive license to the patents at issue in the lawsuit.

Corporate Information

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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 1. Business