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Item 1. Business

2024-03-27 compared with 2023-03-09 · 183 added, 146 removed, 663 unchanged (33% of the section changed)

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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.

The COVID-19 pandemic, including variants thereof, has created uncertainties in the expected timelines for clinical stage biopharmaceutical companies such as us, and because of such uncertainties, it is difficult for us to accurately predict expected outcomes.

While we have commenced dosing in our CLOVER-WaM pivotal clinical study of iopofosine in Waldenstrom’s macroglobulinemia (WM), we have experienced material delays in patient recruitment and enrollment as a result of continued resourcing issues related to COVID-19 at study sites and potentially resulting from concerns among patients about participating in clinical studies during a public health emergency.

The COVID-19 pandemic is also affecting the operations of third parties upon whom we rely.

We are unable to predict how the COVID-19 pandemic may affect our ability to successfully progress our CLOVER-WaM pivotal clinical study or any other clinical programs in the future.

Moreover, there remains uncertainty relating to the trajectory of the pandemic and whether it may cause further delays in patient study recruitment.

The impact of related responses and disruptions caused by the COVID-19 pandemic may result in difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing studies and the incurrence of unforeseen costs as a result of disruptions in clinical supply of iopofosine or preclinical study or clinical study delays and our ability to obtain additional financing.

The continued impact of COVID-19 on results will largely depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the ultimate geographic spread of the disease or variants thereof, the duration of the pandemic, vaccination rates, travel restrictions and social distancing in the U.S., Canada and other countries, business closures or business disruptions, the ultimate impact on financial markets and the global economy, and the effectiveness of actions taken in the U.S., Canada and other countries to contain and treat the disease.

In October 2021, we announced that we are collaborating with BBK Worldwide to provide new concierge services for patients participating in our clinical studies.

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 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 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 WM patients that were r/r to two prior lines of therapy including Bruton tyrosine kinase inhibitor (BTKi) failed or suboptimal response WM patients.

Our lead PDC therapeutic, iopofosine I 131 (iopofosine) 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 and radiotherapeutics.

Our CLOVER-WaM Phase 2 pivotal study of iopofosine in patients with relapsed/refractory (r/r) Waldenstrom’s macroglobulinemia (WM) has completed, and our Phase 2b studies in r/r multiple myeloma (MM) patients and r/r central nervous system lymphoma (CNSL) are ongoing.

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 enrolling.

Additionally, a Phase 1 Investigator-initiated study conducted by the University of Wisconsin Madison of iopofosine I 131 in combination with external beam radiation in patients with recurrent head and neck cancer has also completed.

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

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

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 CLOVER-WaM study was a pivotal registration study evaluating iopofosine in WM patients that were r/r to at least two prior lines of therapy including having failed or had a suboptimal response to a Bruton tyrosine kinase inhibitor (BTKi).

The study completed enrollment in the fourth quarter of 2023, and initial top line data from the study was reported in January 2024.

CLOVER-WaM was a single-arm study with a target enrollment of 50 patients.

Topline safety data was reported on 45 patients meeting criteria for the modified Intent to Treat (mITT) population with a data cut-off date of January 3, 2024.

Topline efficacy evaluable population (41) is defined as patients who are in the mITT and had follow up of at least 60 days post last dose.

The CLOVER-WaM study met its primary endpoint with a major response rate (MRR) of 61% (95% confidence interval [44.50%, 75.80%, two-sided p value < 0.0001]) exceeding the FDA agreed-upon statistical hurdle of 20%.

The overall response rate (ORR) in evaluable patients was 75.6%, and 100% of patients experienced disease control.

Responses were durable, with median duration of response not reached and 76% of patients remaining progression free at a median follow-up of eight months.

These outcomes exceed real world data, which demonstrate a 4-12% MRR and a duration of response of approximately six months or less despite continuous treatment in a patient population that is less pretreated and not refractory to multiple classes of drugs.

Notably, iopofosine I 131 monotherapy achieved an 7.3% complete remission (CR) rate in this highly refractory WM population.

Iopofosine I 131 was well tolerated and its toxicity profile was consistent with the Company's previously reported safety data.

There were no treatment-related adverse events (TRAEs) leading to discontinuation.

The rates of Grade 3 or greater TRAEs observed in more than 10% of patients included thrombocytopenia (55%), neutropenia (37%), and anemia (26%).

All patients recovered from cytopenias with no reported aplastic sequalae.

Importantly, there were no clinically significant bleeding events, and the rate of febrile neutropenia was 2%.

There were no treatment-related deaths in the study.

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, and rhabdomyosarcoma) and lymphoma or recurrent or refractory malignant brain tumors (high grade glioma, 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).

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

This study is partially funded (~$2M) by a National Institutes of Health SBIR grant from the National Cancer Institute.

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).

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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.

The European Commission granted ODD to iopofosine for treatment of r/r MM and WM, as well as PRIME designation for WM.

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.

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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.

Our product pipeline also includes a PDC-based alpha-emitter radiotherapeutic series (CLR12120) in IND enabling studies, preclinical PDC small molecule chemotherapeutic programs, an oligo-conjugate program, a peptide-conjugate program, and several partnered PDC assets.

We are evaluating the CLR 12120 series with multiple alpha emitting isotopes, such as actinium and astatine in both solid and hematologic malignancies.

The other programs are being developed for solid tumors.

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

Through research and development collaborations, our strategy is to generate near-term capital, supplement internal resources, gain access to novel molecules or payloads, accelerate product candidate development, and broaden our proprietary and partnered product pipelines.

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 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 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 a specific cell surface epitope or antigen as are required by other targeted delivery platforms but rather a unique change in the tumor cell membrane.

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

Tumor cells modify the cell membrane to create specific, highly organized microdomains by which to transport lipids and long chain fatty acids into the cytoplasm, 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.

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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.

In addition to the benefits provided by the mechanism of entry, PDCs offer the ability to conjugate payload molecules in numerous ways, thereby increasing the types of molecules selectively delivered via the PDC.

The PDC platform features include the capacity to link with almost any molecule, provide a significant increase in targeted oncologic payload delivery and the ability to target all types of tumor cells.

As a result, we believe that we can generate PDCs to treat a broad range of cancers with the potential to improve the therapeutic index of oncologic drug payloads, enhance or maintain efficacy while also reducing adverse events by minimizing drug delivery to healthy cells, and increasing delivery to cancerous cells and cancer stem cells.

Additionally, molecules targeting specific cell surface epitopes face challenges in completely eliminating a tumor because the targeted antigens are limited in the total number presented on the cell surface, limiting total potential uptake and resulting in heterogenous uptake across the tumor, have longer cycling time from internalization to relocation 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, further increasing the unequal distribution of the drug across the tumor.

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

Additionally, the epitope utilized is also present on other normal tissue, resulting in off-target toxicities.

Beyond the benefits provided by the mechanism of entry, the PDC platform features include the capacity to link with almost any molecule, provide a significant increase in targeted oncologic payload delivery, a more uniform delivery, and the ability to target all types of tumor cells.

As a result, we believe that we can create PDCs to treat a broad range of cancers with the potential to improve the therapeutic index of oncologic drug payloads, enhance or maintain efficacy while also reducing adverse events by minimizing drug delivery to healthy cells, and increasing delivery to cancerous cells and cancer stem cells.

We employ a drug discovery and development approach that allows us to efficiently design, research and advance drug candidates.

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

Our iterative process allows us to rapidly and systematically produce multiple generations of incrementally improved targeted drug candidates without the expense of having to generate significant compound libraries.

A description of our PDC product candidates follows:

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

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

Adverse events across all studies have been largely restricted to fatigue (39)% and cytopenias, specifically, thrombocytopenia (75)%, anemia (61), neutropenia (54)%, leukopenia (56)%, and lymphopenia (34)%.

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

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.

Iopofosine was recently evaluated in the completed CLOVER-WaM Phase 2 pivotal study in patients with r/r WM, while evaluation is ongoing in a Phase 2b study in r/r MM and CNS lymphoma patients and the CLOVER-2 Phase 1b study for pediatric patients with high grade gliomas.

Adverse events across all studies have been largely restricted to fatigue (39%), and cytopenias;

specifically, thrombocytopenia (75%), anemia (61%), neutropenia (54%), leukopenia (56%), and lymphopenia (34%).

Fatalities resulting from infection have occurred in patients treated with iopofosine.

The CLOVER-WaM pivotal Phase 2b study completed enrollment of WM patients that have received at least two previous lines of therapy including those that failed or had a suboptimal response to a BTKi therapy in 4Q 2023.

Topline safety data was reported on 45 patients meeting the criteria for the mITT population with a data cut-off date of January 3, 2024.

Topline efficacy evaluable population (n=41) was defined as patients who were in the mITT and had follow up of at least 60 days post last dose.

The CLOVER-WaM study met its primary endpoint with a MRR of 61% (95% confidence interval [44.50%, 75.80%, two-sided p value < 0.0001]) exceeding the agreed-upon statistical hurdle of 20%.

The ORR in evaluable patients was 75.6%, and 100% of patients experienced disease control.

Responses were durable, with median duration of response not reached and 76% of patients remaining progression free at a median follow-up of eight months.

Notably, iopofosine monotherapy achieved a 7.3% complete remission (CR) rate in this highly refractory WM population.

Iopofosine I 131 was well tolerated and its toxicity profile was consistent with the Company's previously reported safety data.

There were no treatment-related adverse events (TRAEs) leading to discontinuation.

The rates of Grade 3 or greater TRAEs observed in more than 10% of patients included thrombocytopenia (55%), neutropenia (37%), and anemia (26%).

All patients recovered from cytopenias with no reported aplastic sequalae.

Importantly, there were no clinically significant bleeding events, and the rate of febrile neutropenia was 2%.

There were no treatment-related deaths in the study.

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 Phase 2b study will evaluate highly refractory MM patients in triple class, quad- and penta-drug 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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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.

CLOVER-2 Phase 1b study is an open-label, international dose-finding study evaluating two different doses and dosing regiments of 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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In December 2019, the FDA and the European Union each granted ODD for iopofosine for the treatment of WM.

In September 2023, the European Union granted PRIME designation for iopofosine for the treatment of r/r WM.

The FDA granted Fast Track designation for iopofosine for the treatment of r/r LPL and WM in May 2020.

As the result of iopofosine’s RPDD designation, we may be eligible to receive a priority review voucher (PRV) if the product receives approval for any of the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma or osteosarcoma.

The FDA may award PRV to sponsors of a product application for a RPDD that meet its specified criteria.

award PRV to sponsors of a product application for a RPDD that meet its specified criteria.

The key criteria to receiving PRV is that the drug be approved for a rare pediatric disease and treat a serious or life-threatening manifestation of the disease or condition that primarily affects individuals under the age of 18.

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Patients with r/r Waldenstrom’s Macroglobulinemia

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 and relapsed or were refractory to two prior lines of therapy including failed or had a suboptimal response to BTKi therapy.

We participated in a Type C guidance meeting with the FDA in September 2020.

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

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

The study is expected to enroll 50 WM patients who have received at least two prior lines of therapy, failed both lines of therapy including having failed or had a suboptimal response to a BTKi (i.e.

Patients in the trial will receive up to 4-doses of iopofosine over two cycles (cycle one days 1, 15, and cycle two days 57, 71) with each dose administered as a 15mCi/m 2 infusion.

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.

The study enrolled 65 WM patients who have received at least two prior lines of therapy, failed both lines of therapy including having failed or had a suboptimal response to a BTKi (i.e.

Patients in the trial received 4-doses of iopofosine over two cycles (cycle one:

days 1, 15, and cycle two:

days 57, 71) with each dose administered as a 15mCi/m 2 infusion.

The primary endpoint of the trial is major response rate (MRR) 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) 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.

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

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

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.

The interim futility and safety assessment occurred in 2022 and the 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.

The study achieved full enrollment in the fourth quarter 2023 and topline safety data was reported on 45 patients meeting the criteria for the mITT population with a data cut-off date of January 3, 2024.

Among mITT patients, median age was 71 years, median IgM level prior to treatment with iopofosine was 2,185, 90% were refractory to either a BTKi (18/36 50%) or anti-CD20 therapy (18/41 40%), with 26.7% multiclass refractory, and 80% of patients were previously treated with a BTKi therapy.

Topline efficacy evaluable population (n=41) was defined as patients who were in the mITT and had follow up of at least 60 days post last dose.

The CLOVER WaM study met its primary endpoint with a major response rate (MRR) of 61% (95% confidence interval [44.50%, 75.80%, two-sided p value < 0.0001]) exceeding the agreed upon statistical hurdle of 20%.

The overall response rate (ORR) in evaluable patients was 75.6%, and 100% of patients experienced disease control.

Responses were durable, with median duration of response not reached and 76% of patients remaining progression free at a median follow-up of eight months.

Notably, iopofosine monotherapy achieved an 7.3% complete remission (CR) rate in this highly refractory WM population.

Iopofosine I 131 was well tolerated and its toxicity profile was consistent with the Company's previously reported safety data.

There were no treatment-related adverse events (TRAEs) leading to discontinuation.

The rates of Grade 3 or greater TRAEs observed in more than 10% of patients included thrombocytopenia (55%), neutropenia (37%), and anemia (26%).

All patients recovered from cytopenias with no reported aplastic sequalae.

Importantly, there were no clinically significant bleeding events, and the rate of febrile neutropenia was 2%.

There were no treatment-related deaths in the study.

Phase 2 Study in Select B-Cell Malignancies

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The planned study enrollment was up to 80 patients.

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.

The study’s primary endpoint was clinical benefit response (CBR), with secondary endpoints of ORR, PFS, time to next treatment (TtNT), median Overall Survival (mOS), 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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Patients in the r/r WM cohort all received TBD of ≥ 60 mCi (25 mCi/m 2 single bolus, 31.25 mCi/m 2 fractionated, 37.5 mCi/m 2 fractionated, or two cycles of mCi/m 2 fractionated) either as a bolus dose or fractionated.

Current data from our Phase 2a CLOVER-1 clinical study show a 100% ORR in 6 WM patients and an 83.3% major response rate with one patient achieving a complete response (CR), which continues at nearly 27 months post- last treatment.

Current data from our Phase 2a CLOVER-1 clinical study show a 100% ORR in six WM patients and an 83.3% major response rate with one patient achieving a complete response (CR), which reached 39 months post-last treatment.

While median treatment free survival (TFS), also known as treatment free remission (TFR), and DOR have not been reached, the average treatment TFS/TFR is currently at 330 days.

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Patients with r/r Multiple Myeloma Cohort

In September 2020, we announced that a 40% ORR was observed in the subset of refractory multiple myeloma patients deemed triple class refractory who received 60 mCi or greater TBD.

In September 2020, we announced that a 40% ORR was observed in the subset of refractory MM patients deemed triple class refractory who received 60 mCi or greater TBD.

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

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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.

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 May 2021.

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

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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.

In a subset of five 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.

No patients experienced treatment emergent adverse events 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).

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The most frequently reported adverse events in all patients were cytopenias, which followed a predictable course and timeline.

The frequency of adverse events did not increase as doses were increased and the profile of cytopenias remains consistent.

The frequency of adverse events did not increase as doses were increased and the profile of cytopenias remained consistent.

Importantly, our assessment is that these cytopenias have had a predictable pattern to initiation, nadir and recovery and are treatable.

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Based upon iopofosine being well tolerated across all dose groups, the observed response rate, and especially in difficult to treat patients such as high risk and triple class refractory or penta-refractory, and corroborating data showing the potential to further improve upon current ORRs and durability of those responses, the study has been expanded to test a two-cycle dosing optimization regimen with a target TBD > 60 mCi/m 2 of iopofosine.

In May 2020, we announced that the FDA granted Fast Track Designation for iopofosine in WM in patients having received two prior treatment regimens or more.

In May 2020, we announced that the FDA granted Fast Track Designation for iopofosine in WM in patients having received two or more prior treatment regimens.

Phase 1 Study in Patients with r/r Multiple Myeloma

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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).

For the trial, which used a modified three-plus-three 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.

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 free light chain (FLC) was also observed.

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

MM is an incurable cancer of the plasma cells and is the second most common form of hematologic cancer.

Patients had to be refractory to or relapsed from at least one proteasome inhibitor and at least one immunomodulatory agent.

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We use the International Myeloma Working Group (IMWG) definitions of response, which involve monitoring the surrogate markers of efficacy, M protein and FLC.

The IMWG defines a PR as a greater than or equal to 50% decrease in FLC levels (for patients in whom M protein is unmeasurable) or 50% or greater decrease in M protein.

Multiple myeloma is an incurable cancer of the plasma cells and is the second most common form of hematologic cancer.

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

The IMWG defines a PR as a 50% or greater decrease in M protein or to 50% or greater decrease in FLC levels (for patients in whom M protein is unmeasurable).

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

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

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In late 2018, we modified this study to evaluate a fractionated dosing strategy to potentially increase efficacy and decrease adverse events.

Cohort 5 and cohort 6 received fractionated dosing of 31.25 mCi/m 2 (~62.5mCi TBD) and 37.5 mCi/m 2 (~75mCi TBD), each administered on day 1 and on day 8.

Following the determination that all prior dosing cohorts were tolerated, we initiated a cohort 7 utilizing a 40mCi/m2 (~95mCi TBD) fractionated dose administered 20mCi/m2 (~40mCi TBD) on days 1 and day 8.

Cohort 7 was the highest pre-planned dose cohort and subjects have completed the evaluation period.

Cohorts five and six received fractionated dosing of 31.25 mCi/m 2 (~62.5mCi TBD) and 37.5 mCi/m 2 (~75mCi TBD), each administered on day 1 and day 8.

Following the determination that all prior dosing cohorts were tolerated, we initiated a cohort seven utilizing a 40mCi/m2 (~95mCi TBD) fractionated dose administered 20mCi/m2 (~40mCi TBD) on days 1 and day 8.

Cohort seven was the highest pre-planned dose cohort and subjects have completed the evaluation period.

The study completed enrollment and the final clinical study report is expected in the first half of 2022.

Adverse events occurring in at least 25% of subjects were fatigue (26%) and cytopenias, specifically, thrombocytopenia (90%), anemia (65%), neutropenia (55%), leukopenia (61%), and lymphopenia (58%).

Serious adverse events occurring in greater than 2 subjects were restricted to febrile neutropenia n=3 (9.7)%.

Serious adverse events occurring in greater than two subjects were restricted to febrile neutropenia n=3 (9.7%).

In May 2019, we announced that the FDA granted Fast Track Designation for iopofosine in fourth line or later r/r MM.

Iopofosine is currently being evaluated in our ongoing CLOVER-1 Phase 2 clinical study in patients with r/r MM and other select B-cell lymphomas.

Patients in the study received up to 4, approximately 20-minute IV infusions of iopofosine over 3 months, with doses given 14 days apart in each cycle and a maximum of 2 cycles.

Patients in the study received up to four, approximately 20-minute, IV infusions of iopofosine over 3 months, with doses given 14 days apart in each cycle and a maximum of two cycles.

Low dose dexamethasone 40 mg weekly (20mg in patients ≥ 75), was provided for up to 12 weeks.

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Changes in various tumor parameters appeared to demonstrate initial response and tumor uptake.

This includes patients with relapsed HGGs with over 5 months of PFS.

This includes patients with relapsed HGGs with over five months of PFS.

In November 2020, we announced clinical data providing that iopofosine had been measured in pediatric brain tumors, confirming that systemic administration of iopofosine crosses the blood brain barrier and is delivered into tumors and that the data show disease control in heavily pretreated patients with ependymomas.

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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.

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

In 2022, the NCI awarded Cellectar a $1,900,000 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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The reduction in the amount or fractions (doses) of EBRT has the potential to diminish the (number and severity of) adverse events associated with EBRT.

Patients with HNC typically receive approximately 60-70 Grays (Gy) of EBRT given as 2 – 3 Gy daily doses over a 6-week timeframe.

Patients with HNC typically receive approximately 60-70 Grays (Gy) of EBRT given as 2 – 3 Gy daily doses over a six-week timeframe.

Patients can experience long-term tumor control following re-irradiation in this setting;

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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%).

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

This portion of the study has fully enrolled, and data were reported at the ASTRO 2024 conference on March 2, 2024.

Complete remission was achieved in 64% of patients, with an ORR of 73% (n=11).

Prior to treatment with iopofosine I 131, six patients had multiple recurrence and one had metastatic disease, both of which are indicative of poor outcomes.

Additionally, the study demonstrated durability of tumor control with an overall survival of 67% and progression free survival of 42% at 12 months.

Eleven patients (92%) experienced a treatment-related adverse event.

Treatment-related adverse events of grade 3 or higher occurring in 20% or more patients were thrombocytopenia (75%), lymphopenia (75%), leukopenia (75%), neutropenia (67%), and anemia (42%).

Observed adverse events were consistent with the known toxicity profile of iopofosine I 131, with cytopenias being the most common.

All patients recovered.

We believe that these data support the notion of enhanced patient outcomes when combining the use of iopofosine I 131 in combination with external beam radiation for a treatment of solid tumors.

Preclinical Pipeline

We believe our PDC platform has potential to provide targeted delivery of a diverse range of oncologic payloads, as exemplified by the product candidates listed below, that may result in improvements upon current standard of care (SOC) for the treatment of a broad range of human cancers:

● CLR 1900 Series is an internally developed proprietary PDC program leveraging a novel small molecule cytotoxic compound as the payload.

The payload inhibits mitosis (cell division) and targets a key pathway required to inhibit rapidly dividing cells that results in apoptosis.

We believe that this program could produce a product candidate targeted to select solid tumors.

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

● 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 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.

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

The company has validated the in vivo potential of alpha emitting phospholipid radioconjugates and their potential to treat highly refractory and difficult to treat solid tumors.

Cellectar is currently progressing with a lead molecule using actinium-225 as the alpha emitting payload.

● The company has developed a series of proprietary small molecule phospholipid drug conjugates.

These programs employ either novel payload or novel linkers.

Many of these molecules have demonstrated efficacy and tolerability in preclinical mouse models.

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.

● In collaboration with other parties, Cellectar has also validated that the PLE is capable of delivering peptide payloads and oligonucleotide (siRNA, mRNA, etc.) payloads to the tumors when delivered systemically.

These molecules have also been shown to demonstrate activity and safety in multiple preclinical mouse models.

Based upon these collaborations and the data, the company has initiated internal proprietary programs with each of these treatment modalities.

Technology Overview

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For example, the cytotoxic radioisotope, iodine-131, can be attached via a stable covalent bond to the PLE resulting in our lead PDC, iopofosine.

Non-radioactive molecules, including many classes of small molecule chemotherapeutic compounds, peptides and other molecules can also be attached to the delivery vehicle.

In parallel to advancing the clinical development of our lead PDC, iopofosine in both adult and pediatric orphan indications;

we remain focused on exploring the creation of additional PDCs ranging from newly discovered to well-characterized anti-cancer agent payloads.

The objective is to develop PDC chemotherapeutics through conjugation of our delivery vehicle and non-targeted anti-cancer agents to improve therapeutic indices and expand potential indications through the targeted delivery of chemotherapeutic payloads.

Initial PDC product candidates include our CLR 1900, 2000 and 12120 series of conjugated compounds currently being researched independently and through partnerships.

Other than CLR 12120, all are small-molecule, cancer-targeting chemotherapeutics in pre-clinical research.

Non-radioactive molecules, including many classes of small molecule chemotherapeutic compounds, oligos, peptides and other molecules can also be attached to the delivery vehicle.

In parallel to advancing the clinical development of our lead PDC, iopofosine, in both adult and pediatric orphan indications, we remain focused on exploring the creation of additional PDCs ranging from newly discovered to well-characterized anti-cancer agent payloads.

small-molecule, peptide, or oligonucleotide cancer-targeting chemotherapeutics in pre-clinical research.

To date, multiple cancer-targeting product profiles have been generated from a single chemical core structure that is the foundation of our technology platform.

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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.

To date, the Company has focused on rare cancers with significant unmet need including WM, MM, sarcomas, and HGG, among others.

Market Overview

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

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

annual incidence is 1,500 – 1,900 with prevalence of approximately 26,000 and 110,000 patients globally.

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

The disease occurs in a type of white blood cell called a B-lymphocyte or B-cell, which normally matures into a plasma cell whose job is to manufacture immunoglobulins (antibodies) to help the body fight infection.

The disease occurs in a type of white blood cell called a B-lymphocyte or B-cell, which normally matures into a plasma cell that plays an important part in the body’s immune system by manufacturing immunoglobulins (antibodies) to help the body fight infection.

In WM, there is a malignant change to the B-cell in the late stages of maturing, and it continues to proliferate into a clone of identical cells, primarily in the bone marrow but also in the lymph nodes and other tissues and organs of the lymphatic system.

These clonal cells over-produce an antibody of a specific class called IgM.

WM cells have characteristics of both cancerous B-lymphocytes (NHL) and plasma cells (multiple myeloma), and they are called lymphoplasmacytic cells.

WM cells have characteristics of both cancerous B-lymphocytes (NHL) and plasma cells (MM), and they are called lymphoplasmacytic cells.

For that reason, WM is classified as a type of non-Hodgkin’s lymphoma called LPL.

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Front-line treatments for WM include rituximab alone or in combination with other agents, including ibrutinib.

In the salvage therapy (second line or later) setting, BTKi’s, and other combinations are considered (bendamustine, proteosome inhibitors, etc.).

In the salvage therapy (second line or later) setting, BTKi’s, and other combinations are considered (bendamustine,

proteosome inhibitors, etc.).

Ibrutinib and zanubrutinib are the only drugs to receive regulatory approval (in 2015 and 2020, respectively) as a salvage therapy;

in late 2019, ibrutinib was approved for front-line treatment in combination with rituximab.

Factors such as long-term cytopenias, age, hyper-viscosity, the need for quick disease control, lymphadenopathy, co-morbidities, and IgM-related end-organ damage are key consideration in the choice of treatment.

Multiple Myeloma

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market remaining the largest potential market.

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.

It is believed the largest growth will occur in patients receiving at least three lines of treatment because of 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 because of 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.

Additionally, the mOS for these patients also decreases by line of therapy and is less than 9 months post third-line treatment.

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.

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

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.

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

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

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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.

Based on the iopofosine Phase 2 product profile demonstrated in DLBCL patients to date treated with a single dose, we believe iopofosine may meet the unmet medical need in the patient population described above as well.

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

Based on the iopofosine Phase 2 product profile demonstrated in DLBCL patients to date treated with a single dose, we believe iopofosine may address the unmet medical need in the patient population described above as well.

Neuroblastoma

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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%.

Survival for those with relapsed or refractory neuroblastoma currently reports as a four-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.

The WHO classifies these as Grade 3 or 4 based on the growth rate, and these tumors are often incurable.

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%.

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

Sarcomas represent a heterogeneous disease group.

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Sarcomas represent 15% of all pediatric tumors and 21% of pediatric solid tumors.

The National Cancer Institute SEER data base estimates that there were 2,060 incidences in 2019.

The National Cancer Institute SEER database estimates that there were 2,060 incidences in 2019.

The median age at diagnosis was 3, the median age of death was 5.

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Sales and Marketing

We plan to pursue and evaluate all available options to develop, launch and commercialize our compounds.

These options presently include but are not limited to either entering into an agreement for a contract sales organization (CSO), or a partnering arrangement with one or more biotechnology or pharmaceutical companies with strong product development and commercialization expertise and distribution infrastructure in the U.S., Europe and/or Japan.

While we currently do not plan to build our own commercial organization for the launch and commercialization of our compounds, we may reconsider our approach in the future.

The US WM market represents approximately $2.1 billion and is a very concentrated market, with 10 states harboring 60% of the WM cases.

Based upon the concentrated nature of the US WM market, we plan to pursue building a scalable and efficient commercial team to commercialize iopofosine.

We are currently exploring options for the WM opportunity outside of the US market, which will seek to establish an arrangement with one or more biotechnology or pharmaceutical companies with strong product development and commercialization expertise and distribution infrastructure in Europe and parts of global markets.

Potential Commercial Competition to Our Current and Future Clinical-Stage Compounds

Currently, many classes of approved products with various mechanisms of action exist, including immune-modulating agents, proteasome inhibitors, histone deacetylase inhibitors, monoclonal antibodies, corticosteroids, and traditional chemotherapeutics for the treatment of liquid and solid tumors.

There also remain a significant number of compounds being researched and developed for the treatment of cancer.

There also remain a significant number of compounds being researched and developed for the

treatment of cancer.

We are focused on the product development and commercialization of adult and pediatric orphan designated indications with unmet clinical need.

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The in vivo animal data demonstrated that the PDC combined with an alpha emitting radioisotope resulted in significant reduction in tumor volumes in all animal models tested.

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.

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

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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Starting in 2018, we no longer used the facility in Madison, Wisconsin for these activities.

The clinical development has been completed primarily through contract research organizations at hospitals and academic centers.

Clinical development has been completed primarily through contract research organizations at hospitals and academic centers.

We have established a collaboration outsourcing model to leverage third-party expertise, accelerate project timelines, improve productivity and limit spend and fixed costs.

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The typical process required by the FDA before a therapeutic drug may be marketed in the U.S.

● pre-clinical laboratory and animal tests, and formulation studies, performed under the FDA’s Good Laboratory Practices regulations, referred to herein as GLP;

● pre-clinical laboratory and animal tests, and formulation studies, performed under the FDA’s Good Laboratory Practices (GLP) regulations;

● submission to the FDA of an IND, which must become effective before human clinical studies may commence;

● approval by an independent institutional review board (IRB) for each clinical site before each clinical trial may be initiated;

● performance of adequate and well-controlled human clinical studies performed under the FDA’s Good Clinical Practices regulations, to evaluate the drug’s safety and effectiveness for its intended uses;

● performance of adequate and well-controlled human clinical studies performed under the FDA’s Good Clinical Practices (GCP) regulations, to evaluate the drug’s safety and effectiveness for its intended uses;

● submission of a marketing application to the FDA for one or more proposed indications;

● review by an FDA advisory committee, if requested by the FDA;

● Satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities in which the drug is manufactured, processed, packed, or held complies with current Good Manufacturing Practices (cGMP), requirements and standards designed to that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality ad purity;

● satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data;

● satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCP and the integrity of the clinical data;

● payment of user fees and securing FDA approval of the NDA;

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During Phase 1, sufficient information about the drug's safety and tolerability, pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies.

In Phase 2, controlled clinical studies are generally conducted in larger groups of patients having the target disease or condition in order to determine the common short-term side effects and risks associated with the drug, and to obtain preliminary data on the safety and effectiveness of the product candidate and optimal dosing.

on the safety and effectiveness of the product candidate and optimal dosing.

This phase also helps determine further the safety profile of the product candidate.

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In addition, as a condition of approval, the FDA may require an applicant to develop a REMS.

REMS use risk minimization strategies beyond the professional labeling to ensure that the benefits of the product outweigh the potential risks.

REMS use risk minimization strategies beyond professional labeling to ensure that the benefits of the product outweigh the potential risks.

To determine whether a REMS is needed, the FDA will consider the size of the population likely to use the product, seriousness of the disease or condition to be treated by the drug, expected benefit of the product, expected duration of treatment, seriousness of known or potential adverse events, and whether the product is a new molecular entity.

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The FDA may request additional information rather than accept an NDA for filing.

In this event, the application must be resubmitted with the additional information.

In this event, the application

must be resubmitted with the additional information.

The resubmitted application is also subject to review before the FDA accepts it for filing.

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In addition, the Fast Track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.

A product may be designated as a Breakthrough Therapy if it is intended, either alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing available therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

substantial treatment effects observed early in clinical development.

The FDA may take certain actions with respect to Breakthrough Therapies, including holding meetings with the sponsor throughout the development process;

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Significant and pervasive continuing legal and regulatory requirements also apply after FDA approval to market under an NDA.

These include, among other things, requirements related to adverse event and other reporting, product advertising and promotion, and ongoing adherence to cGMP requirements, as well as the need to submit appropriate new or supplemental applications and obtain FDA approval for certain changes to the approved product labeling, or manufacturing process.

FDA approval for certain changes to the approved product labeling, or manufacturing process.

The FDA also enforces the requirements of the Prescription Drug Marketing Act and its implementing regulations which, among other things, impose various requirements in connection with the distribution of product samples to physicians.

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If a drug designated as an orphan drug ultimately receives marketing approval for an indication broader than what was designated in its orphan drug application, it may not be entitled to exclusivity.

Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same drug for the same indication is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market demand.

Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the

same drug for the same indication is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market demand.

Pediatric Studies and Exclusivity

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Instead, in support of such applications, a generic manufacturer may rely on the preclinical and clinical testing previously conducted for a drug product previously approved under an NDA, known as the reference listed drug (RLD).

Specifically, in order for an ANDA to be approved, the FDA must find that the generic version is identical to the RLD with respect to the active ingredients, the route of administration, the dosage form and the strength of the drug.

Specifically, for an ANDA to be approved, the FDA must find that the generic version is identical to the RLD with respect to the active ingredients, the route of administration, the dosage form and the strength of the drug.

An applicant may submit an ANDA suitability petition to request the FDA’s prior permission to submit an abbreviated application for a drug that differs from the RLD in route of administration, dosage form, or strength, or for a drug that has one different active ingredient in a fixed combination drug product (i.e., a drug product with multiple active ingredients).

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Pursuant to the Medicaid Drug Rebate Statute (42 U.S.C.

§ 1396r-8(a)(1)), we will be required to participate in the Medicaid Drug Rebate Program (MDRP) in order for federal payment to be available for our products under Medicaid and Medicare Part B.

§ 1396r-8(a)(1)), we will be required to participate in the Medicaid Drug Rebate Program (MDRP) for federal payment to be available for our products under Medicaid and Medicare Part B.

Medicaid is a government health insurance program for eligible low-income adults, children, families, pregnant women, and people with certain disabilities.

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These data include the average manufacturer price and, in the case of single source and innovator multiple source products, the best price for each drug.

In addition to participating in the MDRP, federal law requires manufacturers to participate in the Public Health Service’s 340B drug pricing program in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B.

In addition to participating in the MDRP, federal law requires manufacturers to participate in the Public Health Service’s 340B drug pricing program for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B.

The 340B drug pricing program requires participating manufacturers to agree to charge statutorily defined covered entities no more than the 340B “ceiling price” for the manufacturer’s covered outpatient drugs.

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instead, such pricing is negotiated based on a mandatory disclosure of the contractor’s commercial “most favored customer” pricing.

In addition, pursuant to regulations issued by the DoD to implement Section 703 of the National Defense Authorization Act for Fiscal Year 2008, each of our covered drugs will listed on an agreement with the Defense Health Agency (DHA) under which we will agree to honor the “Big Four” pricing for our products when they are dispensed to TRICARE beneficiaries by TRICARE retail network pharmacies.

In addition, pursuant to regulations issued by the DoD to implement Section 703 of the National Defense Authorization Act for Fiscal Year 2008, each of our covered drugs will be listed on an agreement with the Defense Health Agency (DHA) under which we will agree to honor the “Big Four” pricing for our products when they are dispensed to TRICARE beneficiaries by TRICARE retail network pharmacies.

More specifically, we will agree to provide rebates (or refunds) on such utilization.

Companies are required to enter into a DHA Agreement for “covered drug” products in order for the covered drug to be eligible for DoD formulary inclusion and available to TRICARE beneficiaries without preauthorization.

Companies are required to enter into a DHA Agreement for “covered drug” products for the covered drug to be eligible for DoD formulary inclusion and available to TRICARE beneficiaries without preauthorization.

The formula for determining the rebate is established in the regulations and our DHA agreement and is based on the difference between the annual Non-FAMP and the FCP (as described above, these price points are required to be calculated by us under the VHCA).

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Employees and Human Capital

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.

As of December 31, 2023, we had twenty employees, all of whom were full-time employees.

Of these twenty employees, ten 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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Legal Proceedings

On October 15, 2021, the Company filed a lawsuit against Dr.

Jamey Weichert, a former director and executive officer of the Company (“Dr.

Weichert”) and Dr.

Anatoly Pinchuk, a former employee and consultant of the Company (“Dr.

Pinchuk”) in the U.S.

District Court for the Western District of Wisconsin.

The Company alleged, among other claims, that Dr.

Weichert and Dr.

Pinchuk breached their contractual and fiduciary duties to the Company by diverting intellectual property that rightfully belonged to the Company to a company controlled by Dr.

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 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.

We may be a party to proceedings in the ordinary course of business, however, we do not anticipate that the outcome of such matters and disputes will materially affect our financial statements.

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