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Item 1. Business

2021-03-31 compared with 2020-05-08 · 602 added, 336 removed, 30 unchanged (97% of the section changed)

Actinium Pharmaceuticals Inc.

is a clinical-stage, biopharmaceutical

company applying its proprietary platform technology and deep understanding of radiobiology to the development of novel targeted

therapies known as ARCs or Antibody Radiation-Conjugates.

Radiation is an effective therapeutic modality that is used in the treatment

of over fifty percent of all cancer patients and often combined with chemotherapy and immunotherapy for greater therapeutic effect.

Radiation is typically administered from outside the body, which constrains the amount that can be administered to patients due

to dose-limiting toxicities.

In addition, due to the diffuse nature of the external radiation beam, its usage is limited to solid

tumors and cannot be used in blood cancers, which are diffuse.

ARCs combine the cell-killing ability of a radioisotope payload

with a targeting agent, such as a monoclonal antibody, or mAb, to deliver radiation inside the body to specific cells, to potentially

generate greater efficacy and less toxicity.

ARCs usage is broader than external delivered radiation as they can be used for both

solid tumors and blood cancers.

Blood or hematologic cancers are highly sensitive to radiation and our clinical pipeline is focused

on ARCs targeting the antigens CD45 and CD33, both of which are expressed in multiple hematologic cancers.

Our clinical programs

are focused on two primary areas:

targeted conditioning prior to a cell or gene therapy procedure and therapeutics, either in combination

with other agents or as a monotherapy.

Our product development strategy is actively informed by clinical data with our ARCs in

over 500 patients, including the ongoing SIERRA trial.

Our clinical pipeline has emanated from our AWE, or Antibody Warhead Enabling

technology platform, which is protected by over 110 issued and pending patents, trade secrets and know-how.

Business Overview

Actinium Pharmaceuticals,

is a clinical-stage, biopharmaceutical company applying its proprietary platform technology and deep understanding of radiobiology

to the development of novel targeted therapies known as Antibody Radiation-Conjugates (“ARCs”).

Radiation is an effective

therapeutic modality that is used in the treatment of over fifty percent of all cancer patients and is often combined with chemotherapy,

immunotherapy and other treatments for greater therapeutic effect.

Radiation is typically administered via an external beam source

from outside the body, leading to off-target exposure to normal healthy tissue and organs, which can constrain the amount of radiation

that can be administered to patients due to associated dose-limiting toxicities.

In addition, use of external beam radiation is

largely limited to solid tumors and cannot be used in blood cancers, which are diffuse throughout the body of a patient.

the cell-killing ability of radiation via a radioisotope payload with a targeting agent, such as a monoclonal antibody to deliver

radiation in a precise manner inside the body to specific, targeted cells, to potentially achieve greater efficacy with lower toxicity

than with external beam radiation.

ARCs enable a broader usage of radiation than external beam radiation as they can be used in

the treatment of both solid tumors and blood cancers.

Blood or hematologic cancers are known to be highly sensitive to radiation.

Our clinical pipeline is focused on ARCs targeting the antigens CD45 and CD33, both of which are expressed in multiple hematologic

Our clinical programs are focused on two primary areas:

(1) targeted conditioning prior to a bone marrow transplant (“BMT”),

adoptive cell therapy (“ACT”) such as CAR-T or gene therapy and (2) ARC therapeutic combinations with other agents.

Our product development strategy is actively informed by clinical data with our ARCs in over 500 patients, including our ongoing

Pivotal Phase 3 SIERRA trial.

Our clinical pipeline has emanated from our Antibody Warhead Enabling (“AWE”) technology

platform, which is protected by over 140 issued and pending patents, trade secrets and know-how and is being utilized in a collaborative

research partnership with Astellas Pharma, Inc.

(“Astellas”).

Targeted Conditioning

We are advancing the only multi-target, multi-indication clinical-stage

pipeline for targeted conditioning and the only ARC-based targeted conditioning regimens in development.

Our ARCs for targeted

conditioning are intended to potentially enable improved access to cell-based therapies with curative potential, including BMT,

or bone marrow transplant, ACT, or adoptive cell therapy such as CAR-T, and Gene Therapy, as well as improved outcomes.

To the best of our

knowledge, we are advancing the only multi-target, multi-indication, clinical-stage pipeline for targeted conditioning and the

only ARC-based targeted conditioning regimens in development.

Our ARCs for targeted conditioning are intended to potentially enable

improved access and outcomes to cell-based therapies with curative potential, including BMT, ACT, and Gene Therapy.

in the context of BMT, ACT or Gene Therapy is the act of depleting certain blood and immune-forming cells, including bone marrow

stem cells and, in some cases, diseased cells prior to transplanting new cells into a patient.

stem cells and, in some cases, cancer cells prior to transplanting new cells into a patient.

Currently, conditioning is accomplished

using a combination of chemotherapeutic agents and external radiation.

These non-targeted conditioning regimens may prevent a patient

from receiving a potentially curative therapy and hinder outcomes due to their toxicities.

using a combination of cytotoxic chemotherapeutic agents and external radiation.

These non-targeted conditioning regimens are highly

toxic and may prevent a patient from receiving a potentially curative therapy and hinder outcomes.

ARCs have the potential to increase

patient access and outcomes by way of their ability to selectively deplete targeted cells while sparing normal healthy cells.

use our ARCs at high isotope dose levels to achieve myeloablation, which fully depletes bone marrow stem cells and at lower isotope

dose levels to achieve lymphodepletion, which spares bone marrow stem cells from depletion.

In addition, dosing may be titrated

downward from myeloablative doses to achieve partial myeloablation, which may be appropriate for certain gene therapy programs.

patient access and outcomes by way of their ability to selectively deplete targeted cells while sparing normal healthy cells, resulting

in potentially lower systemic and off-target toxicities.

We use our ARCs both at high isotope dose levels to achieve myeloablation,

which fully depletes bone marrow stem cells and at lower isotope dose levels to achieve lymphodepletion, which spares bone marrow

stem cells from depletion.

In addition, dosing may be titrated downward from myeloablative doses to achieve partial myeloablation,

which may be appropriate for certain gene therapy programs.

CD45 Targeted Conditioning Program

Our CD45 ARC is comprised of the anti-CD45 monoclonal antibody

known as apamistamab (formerly BC8) and the radioisotope I-131 or Iodine-131.

CD45 is an antigen expressed on leukemia, lymphoma

and myeloma cancer cells, as well as nucleated immune cells, but is not expressed outside of the hematopoietic, or blood, system.

This unique expression on blood cancer and immune cells enables simultaneous depletion of both cell types, making CD45 an optimal

antigen for targeted conditioning applications.

CD45 is a cell surface antigen with an average expression of 200,000 copies per

cell, however, it only internalizes at a rate of 10-15%.

We believe our ARC approach is the most effective method to target CD45

positive cells, as the radioisotope payload linear energy transfer can readily ablate a targeted cell without requiring payload

internalization like an antibody drug conjugate or rely on biological effector function processes like a naked antibody.

since CD45 expression level varies from low to high antigen density as the immune cells become more terminally differentiated,

we can selectively condition depending on the therapeutic application, from full myeloablation to transient lymphodepletion, by

adjusting the dose or intensity of the I-131 isotope payload.

Full myeloablation can be achieved with high doses of I-131, as its

energy pathlength and crossfire effect can penetrate into bone marrow niches to target and deplete blood and immune system forming

bone marrow stem cells.

Myeloablation is applicable to autologous or allogeneic BMT and to autologous gene-edited or modified therapies

that can reconstitute a patient’s blood and immune systems.

Alternatively, low doses of I-131 can be transiently lymphodepleting

and spare a patient’s bone marrow stem cells, which we believe is ideal for ACT applications such as CAR-T.

develop our CD45 targeted conditioning program for BMT, ACT and Gene Therapy applications for malignant and non-malignant diseases.

Our CD45 ARC is comprised

of the anti-CD45 monoclonal antibody known as apamistamab (formerly BC8) and the radioisotope Iodine-131 (“I-131”).

CD45 is an antigen expressed on leukemia, lymphoma and myeloma cancer cells, as well as nucleated immune cells including bone marrow

stem cells, but is not expressed outside of the hematopoietic, or blood forming, system.

This unique expression on blood cancer

and immune cells enables simultaneous depletion of both cell types, making CD45 an optimal antigen for targeted conditioning applications.

CD45 is a cell surface antigen with an average expression of 200,000 copies per cell, however, it only internalizes at a rate of

We believe our ARC approach is the most effective method to target CD45 positive cells, as the radioisotope payload linear

energy transfer can readily ablate a targeted cell without requiring payload internalization like an antibody drug conjugate or

without relying on biological effector function processes like a naked antibody.

Furthermore, since CD45 expression level varies

from low to high antigen density as the immune cells become more terminally differentiated, we can selectively condition depending

on the therapeutic application, from full myeloablation to transient lymphodepletion, by adjusting the dose or intensity of the

I-131 isotope payload.

Full myeloablation can be achieved with high doses of I-131, as its energy pathlength and crossfire effect

can penetrate into bone marrow niches to target and deplete blood and immune system forming bone marrow stem cells.

Myeloablation

is applicable to autologous or allogeneic BMT and to autologous gene-edited or modified therapies that can reconstitute a patient’s

blood and immune systems.

Alternatively, low doses of I-131 can be transiently lymphodepleting and spare a patient’s bone

marrow stem cells, which we believe is ideal for ACT applications such as CAR-T.

We intend to develop our CD45 targeted conditioning

program for BMT, ACT and Gene Therapy applications for malignant and non-malignant diseases and believe that multiple radioisotopes

beyond I-131 may be utilized including alpha and beta emitters.

Our lead CD45 targeted

conditioning product candidate is Iomab-B, which uses high doses of I-131 to achieve myeloablative conditioning prior to a BMT.

Iomab-B is currently being studied in the pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory AML, or SIERRA, clinical

trial for targeted conditioning prior to an allogeneic BMT for patients with active, relapsed or refractory (r/r) Acute Myeloid

Leukemia, or AML, who are age 55 or older.

Patients with active, r/r AML are not normally considered eligible for BMT and the SIERRA

trial is the only randomized Phase 3 trial to offer BMT as a treatment option for this patient population.

The SIERRA trial compares

outcomes of patients randomized to receive Iomab-B and a BMT (the study arm) to those patients randomized to receive physician’s

choice of salvage chemotherapy (the control arm).

Salvage chemotherapy is also defined as conventional care, as no standard of

care exists for this patient population.

Patients who fail to achieve a CR or Complete Response on the control arm are ineligible

to proceed to a BMT, but the trial design permits these patients to “cross over”

to receive the study arm treatment

if they meet the eligibility criteria.

The primary endpoint of the SIERRA trial is durable Complete Remission, or dCR, of six months

and the secondary endpoint is one-year Overall Survival, or OS.

When the crossover patients receive Iomab-B and BMT, they have

not achieved remission with their salvage therapy and are considered to be failures for the primary endpoint of the study.

SIERRA trial is currently active at 20 sites in the United States and Canada, which includes many of the leading BMT sites based

We expect to complete enrollment of the SIERRA trial and have topline data that we believe will support the submission

of a Biologics License Application, or BLA, with the U.S.

Food and Drug Administration, or FDA, in 2021.

If approved, our initial

commercial launch would target the leading 50-100 BMT and medical centers that perform the vast majority of BMT’s in the

United States.

In the European Union or EU, we received favorable feedback from the European Medicines Agency or EMA via their

scientific advice program that the trial design, primary endpoint and planned statistical analysis from the SIERRA trial are acceptable

as the basis for a Marketing Authorization Application or MAA.

Additionally, the EMA commented that it does not anticipate the

need for further standalone preclinical toxicology or safety studies.

Overall, transplant procedures in the EU are approximately

fifty percent higher than in the United States with a similar market dynamic with a majority of BMT volume being conducted in a

concentrated number of leading medical centers.

We intend to secure a partner for Iomab-B in the EU.

Safety and feasibility

data from the first 75 patients enrolled on the SIERRA trial, which represents 50% of the total of 150 patients to be enrolled

in the trial, was presented in an oral presentation at the Transplantation & Cellular Therapy Meetings of the American Society

for Transplantation and Cellular Therapy (ASTCT) and Center for International Bone & Marrow Transplant Research (CIBMTER)

in February 2020.

It was reported that 100% of patients (31/31) on the study arm that received a therapeutic dose of Iomab-B received

a BMT, with a median time to BMT of 30 days, and all patients achieved neutrophil and platelet engraftment in a median time of

20 days despite a high median blast count of 30%.

On the control arm, only 18% of patients (7/38) achieved remission after salvage

therapy, and then received a BMT with a median time to BMT of 67 days and median blast count of 26%.

Of the 82% of patients failing

to achieve a CR with conventional care (31/38), 20 patients were eligible to cross over to the study arm.

Iomab-B is currently being studied in the pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory AML (“SIERRA”),

clinical trial for targeted conditioning prior to an allogeneic BMT for patients with active, relapsed or refractory (“r/r”)

Acute Myeloid Leukemia, (“AML”), who are age 55 or older.

Patients with active, r/r AML are not normally considered

eligible for BMT and the SIERRA trial is the only randomized Phase 3 trial to offer BMT as a treatment option for this patient

The SIERRA trial compares outcomes of patients randomized to receive Iomab-B and a BMT (the “study arm”)

to those patients randomized to receive physician’s choice of salvage therapy (the “control arm”).

arm is also defined as conventional care, as no standard of care exists for this patient population and includes over 20 agents

that may be used as single agents or in combination including venetoclax, a targeted Bcl-2 inhibitor, Midostaurin and Sorafenib,

targeted FLT3 inhibitors, hypomethylating agents and cytotoxic chemotherapies.

Patients who fail to achieve a Complete Response

(“CR”) on the control arm are ineligible to proceed to a BMT, but the trial design permits these patients to “cross

to receive the study arm treatment if they meet the eligibility criteria.

The primary endpoint of the SIERRA trial

is durable Complete Remission (“dCR”) of 180 days and the secondary endpoint is Overall Survival (“OS”).

When the crossover patients receive Iomab-B and BMT, they have not achieved remission with their salvage therapy and are considered

to be failures for the primary endpoint of the study.

The SIERRA trial is currently active at 5 sites in the United States and

Canada, which includes many of the leading BMT sites based on volume.

We expect to complete enrollment of the SIERRA trial and

have topline data that we believe will support the submission of a Biologics License Application (“BLA”) with the U.S.

Food and Drug Administration (“FDA”).

If approved, we expect our initial commercial launch would target the leading

50-100 BMT and medical centers that perform the vast majority of BMT’s in the United States.

In the European Union (“EU”),

we received favorable feedback from the European Medicines Agency (“EMA”) via their scientific advice program that

the trial design, primary endpoint and planned statistical analysis from the SIERRA trial are acceptable as the basis for a Marketing

Authorization Application, or MAA.

Additionally, the EMA commented that it does not anticipate the need for further standalone

preclinical toxicology or safety studies.

Overall, transplant procedures in the EU are approximately fifty percent higher than

in the United States with a similar market dynamic, with a majority of BMT volume being conducted in a concentrated number of leading

medical centers.

Currently we intend to secure a partner for Iomab-B in the EU.

The SIERRA trial is powered

to show a two-times difference in the primary endpoint of dCR of at least 180 days at complete enrollment of the planned 150 patients.

The SIERRA trial design allowed for up to two interim analyses of the primary endpoint, exercisable at our discretion and triggered

by an enrollment range of 70 to 110 patients.

In April 2020, we exercised a single ad hoc analysis on a number of patients representing

less than two thirds of full trial enrollment of 150 patients, which required a higher success threshold compared to the two-time

difference in dCR rate at full trial enrollment.

In December 2020, we announced that the independent Data Monitoring Committee

(“DMC”) completed the single ad hoc interim analysis.

Based on the DMC’s review of unblinded data, including the study’s

primary endpoint of dCR of at least 180 days, it was recommended that the study continue as planned to full enrollment of 150 patients.

We did not receive the unblinded primary and secondary endpoint efficacy data from SIERRA.

By exercising only a single interim

analysis, there was a minimal alpha spend resulting in a p-value threshold of 0.046 for the primary endpoint evaluation at full

enrollment of 150 patients.

The SIERRA trial reached 75% enrollment, representing 113 patients, in the third quarter of 2020.

Data from the first

113 patients enrolled in the SIERRA trial, which represents 75% of the total of 150 patients to be enrolled in the trial, was presented

in oral presentations at the American Society of Hematology (“ASH”) Annual Meeting in December 2020 and at the Transplantation &

Cellular Therapy (“TCT”) Meetings of the American Society for Transplantation and Cellular Therapy (“ASTCT”)

and Center for International Bone & Marrow Transplant Research (“CIBMTR”) in February 2021.

It was reported

that 100% of patients (49/49) on the study arm that received a therapeutic dose of Iomab-B received a BMT, with a median time to

BMT of 30 days, and all patients achieved neutrophil and platelet engraftment in a median time of 18 days despite a high median

blast count of 29%.

On the control arm, only 18% of patients (10/57) achieved remission after salvage therapy, and then received

a BMT with a median time to BMT of 67 days and median blast count of 20%.

Of the 82% of patients failing to achieve a CR with conventional

care (47/57), 30 patients were eligible to cross over to receive Iomab-B followed by transplant.

These patients are considered

1 unchanged sentence

All crossover patients who received the therapeutic dose of Iomab-B (30/30)

received a BMT, with a median time to BMT of 64 days and all patients achieved engraftment in a median time of 19 days despite

high median blast count of 35% at time of crossover.

It was also reported that 100-day non-relapse transplant-related mortality

(100-day TRM) of the study or Iomab-B arm was 6% (2/31) of patients that received a BMT compared to 29% of patients (2/7) who

received a BMT after salvage therapy on the control arm.

The universal engraftment rate and low 100-day TRM rate of the Iomab-B

arm resulted in 29 patients potentially evaluable for the primary endpoint compared to 5 patients in the control arm, a nearly

six times difference.

The SIERRA trial is

powered for up to two interim analyses of the primary endpoint exercisable at our discretion and triggered by an enrollment range

of 70 to 110 patients to evaluate, the primary endpoint of dCR of 180 days.

We intend to exercise an ad-hoc analysis, basing our

decision to do so on the data reported from SIERRA thus far and comfort with the pace and current status of enrollment as of April

2020, which could generate topline data for the primary endpoint in late 2020 and early termination of the trial if positive.

Based on the statistical plan of the study, a single ad-hoc analysis would result in a minimal alpha spend of no more than 0.00925,

depending on the number of patients included in the ad-hoc analysis.

Our Iomab-ACT program is

intended for targeted conditioning prior to ACT or Gene Therapy and uses the same 131 I-apamistamab ARC construct as

Iomab-B at varying doses.

At lower doses of one-eighth to one-sixth of the myeloablative dose, it is applicable for lymphodepletion

prior to CAR-T or certain Gene Therapy applications where stem cell myeloablation is not necessary.

received a BMT, with a median time to BMT of 24 days and they achieved engraftment in a median time of 19 days despite high median

blast count of 22% at time of crossover.

It was also reported that 100-day non-relapse transplant-related mortality (100-day TRM)

of the study or Iomab-B arm was only 4% (2/45) of patients that received a BMT compared to 20% of patients (2/10) who received

a BMT after salvage therapy on the control arm.

The universal engraftment rate and low 100-day TRM rate of the Iomab-B arm resulted

in 43 patients potentially evaluable for the primary endpoint compared to 8 patients in the control arm, a greater than five times

Our Iomab-ACT program

is intended for targeted conditioning prior to ACT or Gene Therapy and uses the same I-131-apamistamab ARC construct as Iomab-B

at varying doses.

At lower doses of one-eighth to one-sixth of the myeloablative dose, it is applicable for lymphodepletion prior

to CAR-T or certain Gene Therapy applications where stem cell myeloablation is not necessary.

At higher doses it is applicable

for Gene Therapy applications where stem cell myeloablation is necessary.

We announced a collaboration

with University of California Davis to utilize Iomab-ACT conditioning in an ongoing Phase 1/2 trial with a novel anti-HIV autologous

stem cell gene therapy for patients with HIV-related lymphoma.

This is the first Gene Therapy trial to use an ARC-based conditioning

131 I-Apamistamab has clinical proof of concept as a targeted conditioning regimen for patients with high-risk,

relapsed or refractory lymphoma prior to an autologous stem cell transplant from a previous study, where a favorable safety profile

with no dose-limiting toxicities and minimal non-hematologic toxicities were observed and promising efficacy with median overall

survival not reached (range:

29 months to not reached) and 31% of patients in prolonged remission at a median of 36 months follow

In this study, Iomab-ACT is intended to replace the chemotherapy-based condition regimen known

as BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) to simultaneously kill the patient’s lymphoma cells and deplete

the patient’s stem cells to make room for the transplant.

Upon engraftment, the transplanted gene-modified autologous stem

cells containing three anti-HIV genes are intended to equip the patient with a new immune system that is resistant to the HIV virus.

Iomab-ACT will be substituted for BEAM in the ongoing Phase 1/2 trial and we expect to have clinical proof of concept data in 2021.

We believe our Iomab-ACT

program is highly differentiated when compared to Fludarabine and Cyclophosphamide or Flu/Cy or other chemotherapy-based regimens

that are used as the standard of practice today for lymphodepletion prior to CAR-T.

CD45 is an antigen expressed on certain immune

cell types that are relevant to the mechanism of CAR-T therapies including lymphocytes, regulatory T cells and macrophages that

have been associated with clinical responses that may limit the safety, efficacy and durability of response of these CAR-T therapies

including Cytokine Release Syndrome, or CRS, and neurotoxicity.

Some of these limitations may be attributable to the chemotherapy-based

conditioning agents that are being used prior to CAR-T therapies.

Preclinical data supporting the rational for our Iomab-ACT program

was presented at multiple medical conferences in 2019.

Unlike chemotherapy, preclinical data suggests Iomab-ACT is targeted in

nature and, due to this targeted effect, we expect we can improve CAR-T cell expansion more efficiently, potentially resulting

in responses that are more durable, but also resulting in reduced CAR-T related toxicities.

Importantly, we expect the Iomab-ACT

program construct to enable lymphodepletion through a single-dose, outpatient administration versus Flu/Cy or other chemotherapy-based

lymphodepletion regimens that can require multiple infusion cycles over several days.

Because of this potentially superior profile,

the Iomab-ACT construct could result in improved access to CAR-T therapy and better outcomes.

We intend to begin a clinical trial

with 131 I-apamistamab as a targeted conditioning agent prior to CAR-T, subject to identifying a suitable partner and

we expect to have Phase 1 clinical proof of concept data in 2021.

program is highly differentiated when compared to Fludarabine and Cyclophosphamide (“Flu/Cy”) or other chemotherapy-based

regimens that are used as the standard of practice today for lymphodepletion prior to CAR-T.

CD45 is an antigen expressed on certain

immune cell types that are relevant to the mechanism of CAR-T therapies including lymphocytes, regulatory T-cells and macrophages

that have been associated with clinical responses that may limit the safety, efficacy and durability of response of these CAR-T

therapies including cytokine release syndrome (“CRS”) and neurotoxicity.

Some of these limitations may be attributable

to the chemotherapy-based conditioning agents that are being used prior to CAR-T therapies.

Preclinical data supporting the rational

for our Iomab-ACT program was presented at multiple medical conferences in 2019.

Unlike chemotherapy, Iomab-ACT is targeted in

nature and, due to this CD45-directed targeting, we expect we can improve CAR-T cell expansion, potentially resulting in responses

that are more durable, but also resulting in reduced CAR-T related toxicities.

Importantly, we expect the Iomab-ACT program construct

to enable lymphodepletion through a single-dose, outpatient administration versus Flu/Cy or other chemotherapy-based lymphodepletion

regimens that can require multiple infusion cycles over several days.

Because of this potentially superior profile, the Iomab-ACT

construct could result in improved access to CAR-T therapy and better outcomes.

In October 2020, we

announced a clinical collaboration with Memorial Sloan Kettering Cancer Center (“MSKCC”) to use our Iomab-ACT for targeted

conditioning prior to administration of MSKCC’s 19-28z CD19 targeting CAR-T in patients with relapsed or refractory B-cell

acute lymphoblastic leukemia (“ALL”) or diffuse large B-cell lymphoma (“DLBCL”).

We received grant funding

from the National Institute of Health (“NIH”) to fund this trial with MSKCC being a co-recipient on this grant.

is a first of its kind study to use an ARC-based conditioning regimen with CAR-T therapy.

MSKCC received clearance from the FDA

to initiate this trial and patient enrollment in this study has commenced.

The hypothesized rationale for this study is that Iomab-ACT

will exert an anti-tumor effect on the chemotherapy-refractory B-ALL cells that are sensitive to radiation resulting in reduced

disease burden and simultaneously deplete CD45 expressing immune cells implicated in CAR-T related toxicities, resulting in an

optimal homeostatic environment for the CAR-T cells.

Results with MSKCC’s 19-28z CD-19 CAR-T in 53 patients with r/r B-ALL

published in the New England Journal of Medicine reported complete remissions in 83% (44/53) of patients, which compares favorably

to standard chemotherapy regimens that have complete remission rates of 18% - 45% in this patient population.

Median event-free

survival (EFS) was 6.1 months and median overall survival (OS) was 12.9 months at a median follow up period of 29 months (range

There was a 26% (14/53) rate of Grade 3 or greater CRS and a 42% rate of Grade 3 or 4 neurotoxicity reported.

The study will evaluate the feasibility of using an ARC-based conditioning regimen with CAR-T therapy and will evaluate safety

measures including incidence of CRS and neurotoxicity and efficacy measures including responses and survival outcomes.

concept data from this study is expected in 2021.

In January 2020, we announced

a collaboration with University of California Davis to utilize Iomab-ACT conditioning in an ongoing Phase 1/2 trial with a novel

anti-HIV autologous stem cell gene therapy for patients with HIV-related lymphoma.

We believe this would be the first Gene Therapy

trial to use an ARC-based conditioning regimen.

I-131-Apamistamab has clinical proof of concept as a targeted conditioning regimen

for patients with high-risk, relapsed or refractory lymphoma prior to an autologous stem cell transplant from a previous study,

where a favorable safety profile with no dose-limiting toxicities and minimal non-hematologic toxicities were observed and promising

efficacy with median overall survival not reached (range:

29 months to not reached) and 31% of patients in prolonged remission

at a median of 36 months follow up (range:

In this study, Iomab-ACT is intended to replace the chemotherapy-based

condition regimen known as BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) to simultaneously kill the patient’s

lymphoma cells and deplete the patient’s stem cells to make room for the transplant.

Upon engraftment, the transplanted gene-modified

autologous stem cells containing three anti-HIV genes are intended to equip the patient with a new immune system that is resistant

to the HIV virus.

We continue to identify additional gene therapies for which Iomab-ACT can be used for targeted conditioning with

the goal of collaborating with multiple academic or industry developers to establish Iomab-ACT as a non-chemotherapy universal

targeted conditioning solution.

In March 2021, we announced

an Ac-225-based CD45 ARC, a next-generation targeted conditioning agent.

Dosimetry results with this Ac-225-based alpha emitting

ARC showed selective accumulation in immune cell target organs such as bone marrow, spleen, and liver with the potential for lower

exposure to non-target tissues from longer path length beta emitter radioisotopes like Iodine-131 and Lutetium-177.

data demonstrated that conditioning with this Ac-225-based CD45-targeting agent result in depletion of peripheral immune cells

and hematopoietic progenitor cells, thereby enabling engraftment of donor cells.

A dose dependent response was observed with low

doses depleting white blood without effecting hematopoietic progenitor cells, representing a lymphodepletive dose that is relevant

for adoptive cell therapies such as CAR-T, while higher doses eliminated peripheral immune cells and hematopoietic progenitor cells,

which is applicable to ex vivo gene therapies and BMT.

CD33 Program:

Targeted Conditioning, Combinations

and Therapeutics

Combinations Trials and Targeted

Our CD33 program is evaluating

the clinical utility of an ARC comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225

CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as approximately

one third of patients with multiple myeloma.

Our CD33 development program is driven by data obtained from over one hundred treated

patients, including results from a Phase 1/2 trial that was conducted in 58 patients with newly diagnosed AML, which was completed

This clinical data, as well as our experience with Iomab-B, is shaping a two-pronged approach with our CD33 program,

where at high doses we are exploring its use for targeted conditioning and at low doses we are exploring its use for therapeutic

purposes as a single agent, or in combination with other modalities.

Actimab-MDS is our

second clinical trial focused on targeted conditioning, in this case for patients with high-risk MDS and is our second pivotal

Actimab-MDS is informed by prior experience with our CD33 ARC in multiple trials for patients with AML, MDS and for patients

that have progressed from MDS to AML, which is also known as secondary AML.

Data from these trials showed that our CD33 ARC had

single-agent activity capable of producing complete remissions (CRs) in certain patients at varying dose levels with minimal non-hematologic

the clinical utility of Actimab-A, an ARC comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope

Actinium-225 (“Ac-225”).

CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome (“MDS”)

as well as approximately one-third of patients with multiple myeloma.

Our CD33 development program is driven by data obtained from

nearly one hundred fifty treated patients, including results from a Phase 1/2 trial that was conducted in 58 patients with newly

diagnosed AML, which was completed in 2018.

This clinical data, as well as our experience with Iomab-B, is shaping a two-pronged

approach with our CD33 program, where at high doses we are exploring its use for targeted conditioning and at low doses we are

exploring its use for therapeutic combinations with other treatment modalities.

We believe that radiation

via an ARC can be synergistic when used in combination with chemotherapy, targeted agents and immunotherapy based on mechanistic

rationales supported by our own clinical data, preclinical research and scientific and clinical evidence in the literature.

have prioritized our efforts and resources in favor of combination trials for our CD33 program development strategy rather than

single agent trials at this time.

Our CD33 ARC development program encompasses the following ongoing trials:

Combination Trials :

Phase 1 investigator initiated Actimab-A + CLAG-M combination trial with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for fit patients age 18 and above with relapsed or refractory AML at the Medical College of Wisconsin (“MCW”).

The combination of Actimab-A + CLAG-M is supported by mechanistic rationale for combining inhibitors of DNA replication and/or repair processes such as mitoxantrone, a topoisomerase-II inhibitor, and radiation, as imparted by tumor-targeting of Ac-225 with Actimab-A.

In September 2020, we announced that we completed the third and planned final dose cohort of 0.75 µCi/kg of Actimab-A.

At the 2020 American Society of Hematology Annual Meeting, it was reported that 100% of patients (3/3) receiving 0.75 µCi/kg of Actimab-A, and CLAG-M achieved a complete remission, which is nearly 85% greater than the 55% remission rate observed in a study of CLAG-M alone conducted at MCW in the same r/r AML patient population.

Complete Remission (“CR”) or Complete Remission with Incomplete blood count recovery (“CRi”) were observed in all dose cohorts (0.25, 0.50 and 0.75 µCi/kg) with 67% of patients (10/15) achieving CR or CRi.

The 0.25 and 0.50 µCi/kg doses of Actimab-A have been shown to be subtherapeutic as a single agent.

Of the 10 patients achieving CR or Cri, 70% achieved negative minimal residual disease (“MRD) status with no detectable disease via flow cytometry, indicating that these are deep remissions.

No dose-limiting toxicities (“DLTs”) were reported in the third dose cohort of 0.75 µCi/kg and therefore maximum tolerable dose (MTD) was not reached.

As a result, MCW amended the study protocol to allow for continued dose escalation and the trial is now enrolling patients at a dose of 1.0 µCi/kg.

Upon completion of this Phase 1 trial, we will work to develop a regulatory and development pathway that can potentially support a registration for the Actimab-A + CLAG-M combination.

In addition, the Actimab-A + CLAG-M combination study has provided proof of principle that the addition of subtherapeutic doses of Actimab-A to other AML therapies can lead to well-tolerated regimens with improved responses.

Phase 1/2 Actimab-A + Ven combination trial with the BCL-2 inhibitor Venetoclax (“ven”) for fit and unfit patients age 18 and above with relapsed or refractory AML.

This multi-center trial is being led by UCLA Medical Center.

In September 2020, we announced that we successfully completed enrollment of the first dose cohort and are continuing to advance to the next cohort of this dose-escalation trial.

This combination is supported by mechanistic evidence in preclinical studies using ven-resistant AML tumor cell lines.

In these models, we have demonstrated that Actimab-A can deplete Mcl-1 and Bcl-XL, two proteins implicated in mediating resistance to venetoclax, in addition to causing potentially lethal double-stranded DNA breaks in these CD33 expressing cells.

Furthermore, in vivo studies in animal models of ven-resistant AML demonstrated robust tumor regression and improved survival in cohorts receiving the Actimab-A ven combination compared to ven alone.

The rationale for this clinical study is that the addition of Actimab-A will;

1) have a direct anti-tumor effect via double-stranded DNA breaks and 2) deplete Mcl-1 and BCL-XL making the AML cells more susceptible to ven.

At the 2020 ASH annual meeting, data from the first dose cohort of 0.50 µCi/kg Actimab-A in combination with ven were presented.

There was a 67% overall response rate (2/3 patients), including one CR and one partial response (“PR”) with blast count reduction of 50%.

All 3 patients were poor risk with adverse cytogenetics and each patient had an additional high-risk marker (FLT3-ITD+, antecedent JAK2+ myelofibrosis, or TP53 mutation).

The patient achieving a CR was in second relapse and a TP53 mutation as well as multiple other high-risk markers.

The trial is now active and recruiting at 4 trial sites in dose escalation cohorts.

We expect to have Phase 1 safety and preliminary proof of concept clinical data from this combination study in 2021.

In addition to these active

trials, we are working to identify additional modalities and agents that can be the basis for Actimab-A therapeutic combinations.

Targeted Conditioning :

Actimab-MDS is our second

clinical trial focused on targeted conditioning, in this case for patients with high-risk MDS and is our second pivotal program.

Actimab-MDS is informed by prior experience with our CD33 ARC in multiple trials for patients with AML, and for patients that have

progressed from MDS to AML, which is also known as secondary AML.

Data from these trials showed that our CD33 ARC had single-agent

activity capable of producing complete remissions (CRs) in certain patients at varying dose levels with minimal non-hematologic

extramedullary toxicities.

9 unchanged sentences

Based on our interactions with FDA to date,

we will conduct a Phase 1 dose-finding clinical trial that will be followed by a randomized trial that, depending on the results

observed, may potentially serve as a pivotal trial to support the submission of a Biologics License Application, or BLA.

currently finalizing discussions with the FDA.

Our CD33 development program

is also studying the construct at various dose levels and dosing regimens either in combination or alone in multiple hematologic

disease indications.

We currently have multiple clinical trials ongoing, in startup phase and in planning, to study our CD33 ARC

in combination with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy.

We believe that radiation

can be synergistic when used in combination with these modalities based on mechanistic rationale supported by our own clinical

data, preclinical research and scientific evidence in the literature.

We are also studying our CD33 ARC as a monotherapy in the

case of multiple myeloma, or MM.

Our CD33 ARC development program encompasses the following ongoing and planned trials:

Combination Trials :

Phase 1 investigator initiated Actimab-A + CLAG-M combination trial with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for patients with relapsed or refractory AML at the Medical College of Wisconsin.

At the 2019 American Society of Hematology Annual Meeting, it was reported that 86% of patients (6/7) receiving 0.50 µCi/kg of Actimab-A, and CLAG-M achieved a complete remission after receiving Actimab-A + CLAG-M, which is nearly 60% greater than the 55% remission rate observed in a study of CLAG-M alone conducted at MCW in the same r/r AML patient population.

In addition, 71% of these patients (5/7) achieved negative minimal residual disease status, indicating that these are deep remissions.

The 0.50 µCi/kg dose of Actimab-A was shown to be subtherapeutic as a single agent., Since the combination to date has been well tolerated, the study progressed to the third and final cohort that will study Actimab-A at a dose of 0.75 µCi/kg in March 2020 and we expect to complete this trial by the end of 2020.

Upon completion, we intend to explore a regulatory pathway for a pivotal trial that could potentially support a registration.

The Actimab-A + CLAG-M combination study has provided proof of principle that the addition of subtherapeutic doses of Actimab-A to other AML therapies can lead to well tolerated regimens with improved responses.

Phase 1 Actimab-A + Ven combination trial with the BCL-2 inhibitor Venetoclax (Ven) for patients with relapsed or refractory AML.

This trial will be led by UCLA Medical Center and will be conducted at three additional trial sites.

This combination is supported by mechanistic evidence in preclinical studies using Ven-resistant AML tumor cell lines.

Furthermore, in vivo studies in animal models of Ven-resistant AML demonstrated robust tumor regression and improved survival in cohorts receiving the Actimab-A Ven combination compared to Ven alone.

The rationale for this clinical study is that the addition of Actimab-A will;

1) have a direct anti-tumor effect via double-stranded DNA breaks and 2) deplete Mcl-1 and BCL-XL making the AML cells more susceptible to Ven.

We expect to initiate the trial and have preliminary proof of concept clinical data from this combination study by the end of 2020.

Phase 1 Actimab-A + 7+3 combination trial in patients with newly diagnosed AML with intermediate or high-risk cytogenetics or molecular markers.

In February 2020, we announced plans to initiate this combination trial to add Actimab-A to 7+3, which is the standard of care chemotherapy regimen comprised of cytarabine and daunorubicin for patients with newly diagnosed AML who are fit for intensive therapy.

As we have seen with the combination of Actimab-A + CLAG-M chemotherapy, we believe that Actimab-A will have synergistic and potentiating properties when added to 7+3, which causes DNA damage and has radiation sensitizing properties since daunorubicin is an anthracycline antibiotic that cytotoxically inhibits DNA replication and repair and RNA synthesis through inhibition of topoisomerase II.

The rationale for studying Actimab-A in combination with 7+3 is the potential for both additive and synergistic effects due to the interplay of various mechanisms including DNA damage from alpha radiation and the chemotherapy combination, radiation sensitization, and prevention of DNA damage repair.

We expect to initiate this Phase 1 trial by the end of 2020 and have proof of concept data in 2021.

Monotherapy Trial :

Multi-center Phase 1 Actimab-M trial for patients with penta refractory MM.

Approximately one third of patients with MM have CD33 expression, which is associated with poorer outcomes.

MM is exquisitely sensitive to radiation, but patients do not receive radiation currently because external delivery could result in significant toxicities given that the disease is spread throughout the body.

The rationale for this trial is to use a new therapeutic modality of alpha radiation, which MM cells have no known resistance mechanism against, for this high-risk patient population.

We have recently initiated Memorial Sloan Kettering Cancer Center as a clinical trial site in the Actimab-M trial, which is currently active at three other trial sites in the United States.

We expect to have initial proof of concept data from this trial in 2021.

we intend to conduct a Phase 1 dose-finding clinical trial that can be followed by a randomized trial that, depending on the results

observed, may potentially serve as a pivotal trial to support the submission of a BLA.

Antibody Warhead Enabling Technology Platform

Our proprietary Antibody

Warhead Enabling, or AWE, Technology Platform is supported by intellectual property, know-how and trade secrets that cover the

generation, development, methods of use and manufacture of ARCs and certain of their components.

Our AWE technology patent portfolio

includes 28 patent families comprised of over 110 issued and pending patent applications, of which 9 are issued and 23 pending

in the United States, and 81 are issued and pending internationally.

The effective life of the patents in our portfolio range

from expirations between 2020 to 2039.

Our technology enables the direct labeling, or conjugation and labeling, of a biomolecular

targeting agent to a radionuclide warhead and its development and use as a therapeutic regimen for the treatment of diseases such

Our AWE intellectual property covers various methods of use for ARCs in multiple diseases, including indication, dose

and scheduling, radionuclide warhead, and therapeutic combinations.

Property Portfolio and Regulatory Protections

We have developed or

in-licensed numerous patents and patent applications and possess substantial know-how and trade secrets related to the development

and manufacture of our products.

As of May 2020, our patent portfolio includes:

28 patent families comprised of 122 issued and

pending patent applications, of which 9 are issued and 22 are pending in the United States, and 91 are issued and pending internationally.

Several non-provisional patent applications are expected to be filed in 2020 based on provisional patent applications filed in

More than 90% of our patents are Actinium-owned and the remainder are in-licensed from third parties.

These patents cover

key areas of our business, including use of actinium-225 and other alpha- or beta-emitting isotopes attached to cancer specific

carriers like monoclonal antibodies, methods for manufacturing key components of our product candidates including actinium-225,

an alpha particle emitting radioisotope and carrier antibodies, or Iodine-131, a beta particle emitting radioisotope, and methods

for manufacturing finished product candidates for use in cancer treatment.

Our proprietary AWE Technology

Platform is supported by intellectual property, know-how and trade secrets that cover the generation, development, methods of use

and manufacture of ARCs and certain of their components.

Our AWE technology patent portfolio includes 34 patent families comprised

of over 140 issued and pending patent applications, of which 10 are issued and 29 are pending in the United States, and 104 are

issued or pending internationally.

The effective life of the patents in our portfolio range from expirations between 2021 and 2040.

Our technology enables the direct labeling, or conjugation and labeling, of a biomolecular targeting agent to a radionuclide warhead

and its development and use as a therapeutic regimen for the treatment of diseases such as cancer.

Our AWE intellectual property

covers various methods of use for ARCs in multiple diseases, including indication, dose and scheduling, radionuclide warhead, and

therapeutic combinations.

We have particular expertise in the area of ARCs utilizing the alpha emitting isotope Ac-225 including

clinical experience in treating approximately 150 patients with our alpha-emitter ARCs, “gold standard”

linker technology

and 5 issued patents in the United States and 49 patents internationally related to the manufacturing or Ac-225 in a cyclotron,

which we believe has the potential to produce higher quantities of Ac-225 then currently utilized methods.

In the third quarter of

2020 we enhanced our research and development capabilities around AWE by securing research facilities that were staffed and became

operational in the fourth quarter.

Our research laboratories are focused on applying our AWE technology platform to the development

of radiation conjugates and to execute on research collaborations.

Our R&D efforts employ a multidisciplinary approach leveraging

our team’s knowledge and experience in cancer cell biology, radiochemistry, radiation sciences, immunology and oncology drug

We intend to focus on generating ARCs using our existing intellectual property, evaluating assets for in-licensing

to complement our existing clinical pipeline and securing collaborations and partnerships with biopharmaceutical companies.

adding research and development capabilities to our clinical development and clinical supply chain capabilities, we seek to enable

the rapid translation of radiotherapies.

We have formed a wholly owned research subsidiary for the purposes of advancing certain

of our R&D objectives.

In January 2021, we announced

a collaborative research agreement with Astellas that will utilize our AWE technology platform will be utilized with select targeting

agents owned by Astellas in the development of theranostics for solid tumor indications, which combine the ability of radioisotopes

to be used for both diagnostic and therapeutic purposes.

Intellectual Property Portfolio and Regulatory Protections

Intellectual Property

We have developed or in-licensed

numerous patents and patent applications and possess substantial know-how and trade secrets related to the development and manufacture

of our products.

As of March 2021, our patent portfolio includes 34 patent families comprised of 143 issued and pending patent

applications, of which 10 are issued and 29 are pending in the United States, and 104 are issued and pending internationally.

non-provisional patent applications are expected to be filed in 2021 based on provisional patent applications filed in 2020.

than 90% of our patents are Actinium-owned and the remainder are in-licensed from third parties.

These patents cover key areas

of our business, including use of actinium-225 and other alpha- or beta-emitting isotopes attached to cancer specific carriers

like monoclonal antibodies, methods for manufacturing key components of our product candidates including actinium-225, an alpha

particle emitting radioisotope and carrier antibodies, or Iodine-131, a beta particle emitting radioisotope, and methods for manufacturing

finished product candidates for use in cancer treatment.

We own five issued patents

including one divisional patent in the United States and 49 patents outside of the United States, including one divisional patent

related to the manufacturing of actinium-225 in a cyclotron, that will expire between 2024 through 2030.

Three related global patents

We own or have licensed the rights to four issued patents in the United States and 8 issued patents outside of the

United States related to the generation of radioimmunoconjugates that will expire between 2021 and 2037.

Twelve related United

States or global patents are pending, Further, we own the rights to 32 additional pending patents in the United States and abroad

related to radioimmunoconjugate composition, formulation administration, and methods of use in solid or liquid cancers.

includes composition, administration, and methods of treatment for our products Actimab-A and Iomab-B.

In addition, for Iomab-ACT,

we own 9 patents pending covering methods of use and composition in cancer and non-malignant disease

indications for which we are developing our product candidates for are orphan drug designations, which are disease indications

that affect fewer than 200,000 patients in the United States and less than 5 in 10,000 patients in the European Union (“EU”).

We have received orphan drug designation for Iomab-B and our lintuzumab-CD33 ARC for patients with AML in both the United States

As a result, if our products are to be approved, they may receive 7 years and 10 years of market exclusivity in the

US and EU, respectively.

In addition, our product candidates are biologics combined with radioisotopes.

The Hatch-Waxman Act requires

that a manufacturer of generic drugs, for which a biologic drug is called a biosimilar, requires that the manufacturer demonstrate

bioequivalence.

We believe that due to the nature of radioisotopes having half-lives combined with the complexities of biologic

drugs would make it difficult for a manufacturer to demonstrate bioequivalence of our product candidates.

In the field of

targeted conditioning, pharmaceuticals currently used for myeloablation prior to a bone marrow transplant or lymphodepletion

prior to CAR-T are largely generic chemotherapeutic agents and/or radiation.

In targeted conditioning, we face competition

from Magenta Therapeutics, Inc., who is developing anti-CD45 and anti-CD117 (cKIT) Antibody Drug Conjugates (ADCs) that are

in the preclinical stage of development and Jasper Therapeutics, Inc, who is developing an anti-CD117 monoclonal antibody

that is being studied in a Phase 1 clinical trial.

Forty Seven, Inc.(acquired by Gilead), who is developing a conditioning

regimen comprised of the anti-CD47 monoclonal antibody Magrloimab that is being studied in a Phase 2 clinical trial as a

therapeutic with an anti-CD117 monoclonal antibody, which is in preclinical development, in collaboration with bluebird bio,

Inc., Molecular Templates, who is developing conditioning regimens using its Engineered Toxin Bodies (ETBs) with two targets

that have not been disclosed in collaboration with Vertex.

Allogene Therapeutics, who is developing an anti-CD52 monoclonal

antibody for use as a lymphodepletion agent in conjunction with CAR-T therapies.

To our knowledge, we are the only company

with a pivotal Phase 3 trial for a targeting conditioning agent and the only anti-CD45 ARC in clinical development.

For our CD33 ARC, there are several companies developing drugs

for AML, MDS and Multiple Myeloma based on numerous approaches/modalities, including chemotherapy, targeted agents, antibody drug

conjugates, naked monoclonal antibodies, bispecific antibodies, immunotherapies and cellular therapies.

Specific to CD33, Mylotarg™,

an ADC developed and marketed by Pfizer is the only FDA approved CD33 targeted therapy for adult patients and children two years

and older with relapsed or refractory CD33-positive AML.

Seattle Genetics was developing SGN-CD33A, a CD33 targeting ADC, but discontinued

the development of its clinical trials associated with this product candidate in June 2017.

Immunogen is also developing a CD33

targeting ADC, IMGN779, that is currently in a Phase 1 clinical trial for r/r AML patients age 18 and above.

Amgen is developing

a CD3/CD33 bispecific BiTE (AMG330) as is Amphivena (AMV-564), both of which are in Phase 1 clinical trials for r/r AML patients

age 18 and above.

Boehringer Ingelheim is developing a CD33 targeting naked antibody (BI836858) for patients with r/r AML or MDS

age 18 and above.

These drugs have different safety profiles and mechanisms of action compared to our drug candidates.

patients remains an area of high medical need that could accommodate many new products with favorable safety and efficiency profiles.

We have begun studying our CD33 ARC in combination with the salvage chemotherapy regimen CLAG-M for patients with relapsed or refractory

Combination therapies are commonly used in hematologic indications, but we believe we are the only Ac-225 based product candidate

that is being explored in combination studies in hematologic indications.

To our knowledge, we are the only company with a CD33

targeting drug and the only AC-225 based ARC product candidate for patients with multiple myeloma.

authorities in the United States and other countries extensively regulate, among other things, the research, development, testing,

manufacture, labeling, promotion, advertising, distribution and marketing of radioimmunotherapy pharmaceutical products such as

those being developed by us.

In the United States, the FDA regulates such products under the Federal Food, Drug and Cosmetic Act

(FDCA) and implements regulations.

Failure to comply with applicable FDA requirements, both before and after approval, may subject

us to administrative and judicial sanctions, such as a delay in approving or refusal by the FDA to approve pending applications,

warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions and/or

criminal prosecution.

in the United States and 49 patents outside of the United States , related to the manufacturing of actinium-225

in a cyclotron, that will expire between 2024 through 2027.

Three related global patents are pending.

We own or have licensed the

rights to five issued patents in the United States and 11 issued patents outside of the United States related to the generation,

formulation, or use of radioimmunoconjugates, including patents related to our Iomab-B and Actimab-A programs, that will expire

between 2021 and 2037.

Thirteen related United States or global patents are pending.

Further, we own the rights to 57 additional

pending patents in the United States and abroad related to radioimmunoconjugate composition, formulation administration, and methods

of use in solid or liquid cancers.

This matter includes composition, administration, and methods of treatment for our products

Actimab-A and Iomab-B.

In addition, for Iomab-ACT, we own 11 patents pending covering methods of use and composition in cancer

and non-malignant disease.

Regulatory Protections

The indications for which

we are developing our product candidates for are orphan drug designations, which are disease indications that affect fewer than

200,000 patients in the United States and less than 5 in 10,000 patients in the EU.

We have received orphan drug designation for

Iomab-B and our lintuzumab-CD33 ARC for patients with AML in both the United States and the EU.

As a result, if our products are

to be approved, they may receive 7 years and 10 years of market exclusivity in the United States and EU, respectively.

our product candidates are biologics combined with radioisotopes.

The Hatch-Waxman Act requires that a manufacturer of generic

drugs, for which a biologic drug is called a biosimilar, demonstrate bioequivalence to the innovator.

We believe that the nature

of radioisotopes having half-lives combined with the complexities of biologic drugs would make it difficult for a manufacturer

to demonstrate bioequivalence to our product candidates.

Competition Overview

In the field of targeted

conditioning, pharmaceuticals currently used for myeloablation prior to a bone marrow transplant or lymphodepletion prior to CAR-T

are largely generic chemotherapeutic agents and/or radiation.

In targeted conditioning, we face competition from Magenta Therapeutics,

Inc., who is developing anti-CD45 and anti-CD117 (cKIT) Antibody Drug Conjugates (ADCs) that are in the preclinical stage of development

and Jasper Therapeutics, Inc, who is developing an anti-CD117 monoclonal antibody that is being studied in a Phase 1 clinical trial.

Forty Seven, Inc.(acquired by Gilead), who is developing a conditioning regimen comprised of the anti-CD47 monoclonal antibody

Magrloimab that is being studied in a Phase 2 clinical trial as a therapeutic with an anti-CD117 monoclonal antibody, which is

in preclinical development, in collaboration with bluebird bio, Inc., Molecular Templates, who is developing conditioning regimens

using its Engineered Toxin Bodies (ETBs) with two targets that have not been disclosed in collaboration with Vertex.

Allogene Therapeutics,

who is developing an anti-CD52 monoclonal antibody for use as a lymphodepletion agent in conjunction with CAR-T therapies.

knowledge, we are the only company with a pivotal Phase 3 trial for a targeting conditioning agent and the only anti-CD45 ARC in

clinical development.

For our CD33 ARC, there

are several companies developing drugs for AML, MDS and Multiple Myeloma based on numerous approaches/modalities, including chemotherapy,

targeted agents, antibody drug conjugates, naked monoclonal antibodies, bispecific antibodies, immunotherapies and cellular therapies.

Specific to CD33, Mylotarg™, an ADC developed and marketed by Pfizer is the only FDA approved CD33 targeted therapy for adult

patients and children two years and older with relapsed or refractory CD33-positive AML.

Seattle Genetics was developing SGN-CD33A,

a CD33 targeting ADC, but discontinued the development of its clinical trials associated with this product candidate in June 2017.

Amgen is developing a CD3/CD33 bispecific BiTE (AMG330) as is Amphivena (AMV-564), both of which are in Phase 1 clinical trials

for r/r AML patients age 18 and above.

Boehringer Ingelheim developed a CD33 targeting naked antibody (BI836858) that was studied

in patients with r/r AML and MDS with the trial in patients with MDS being terminated and development has been discontinued.

drugs have different safety profiles and mechanisms of action compared to our drug candidates.

AML in older patients remains an

area of high medical need that could accommodate many new products with favorable safety and efficiency profiles.

We have begun

studying our CD33 ARC in combination with the salvage chemotherapy regimen CLAG-M in fit patients with relapsed or refractory AML

as well as in combination with the Bcl-2 inhibitor venetoclax in fit and unfit patients with relapsed or refractory AML.

therapies are commonly used in hematologic indications, but we believe we are the only Ac-225 based product candidate that is being

explored in combination studies in hematologic indications.

To our knowledge, we are the only company with a CD33 targeting drug

and the only AC-225 based ARC product candidate for patients with multiple myeloma.

Government Regulation

Governmental authorities

in the United States and other countries extensively regulate, among other things, the research, development, testing, manufacture,

labeling, promotion, advertising, distribution and marketing of radioimmunotherapy pharmaceutical products such as those being

developed by us.

In the United States, the FDA regulates such products under the Federal Food, Drug and Cosmetic Act (“FDCA”)

and implements regulations.

Failure to comply with applicable FDA requirements, both before and after approval, may subject us

to administrative and judicial sanctions, such as a delay in approving or refusal by the FDA to approve pending applications, warning

letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions and/or criminal

Food and Drug Administration Regulation

research, development and clinical programs, as well as our manufacturing and marketing operations, are subject to extensive regulation

in the United States and other countries.

Most notably, products that may in the future be sold in the United States are subject

to regulation by the FDA.

Certain of our product candidates in the United States require FDA pre-marketing approval of a BLA pursuant

Foreign countries may require similar or more onerous approvals to manufacture or market these products.

by us or by our suppliers to comply with applicable regulatory requirements can result in enforcement action by the FDA, the Nuclear

Regulatory Commission or other regulatory authorities, which may result in sanctions, including but not limited to, untitled letters,

warning letters, fines, injunctions, consent decrees and civil penalties;

customer notifications or repair, replacement, refunds,

recall, detention or seizure of our products;

Our research, development

and clinical programs, as well as our manufacturing and marketing operations, are subject to extensive regulation in the United

States and other countries.

Most notably, products that may in the future be sold in the United States are subject to regulation

Certain of our product candidates in the United States will require FDA approval of a BLA prior to marketing.

countries may require similar or more onerous approvals to manufacture or market these products.

FDA Approval Process for Biologics License

Prior to testing a biological

product on humans, the product must clear the preclinical testing stage.

The goal of preclinical testing is to perform laboratory

evaluations of the product’s chemistry and formulation as well as evaluate the product’s potential for adverse events

by performing in vitro and animal studies.

This information is packaged together and submitted to the FDA as part of an investigational

new drug (“IND”) application, which must be approved by the FDA before administering the product to human subjects

in clinical trials.

From there, the product

moves to the clinical stage, where it is administered to healthy volunteers or patients.

The data gathered from the preclinical

testing and clinical trials is used to support the BLA submission.

The FDA must approve the BLA prior to commercial marketing of

a biological product.

The BLA must include information about product development, laboratory and animal studies, human trials,

manufacturing information, the composition of the product, and proposed labeling.

The approval process requires significant time

and financial resources and does not guarantee that FDA will accept the BLA filing or ultimately approve the BLA.

The Prescription Drug User

Fee Act, as amended (“PDUFA”), requires each BLA to be accompanied by a substantial user fee.

The amount of the user

fee changes on an annual basis.

In addition to the BLA user fee, PDUFA also imposes an annual program fee for biological products.

The FDA will waive or reduce the fee under limited circumstances, such as for first applications filed by small businesses.

Within 60 days following

submission of the BLA, the FDA reviews the BLA submission for completion to determine if it will accept it for filing.

may refuse to file the BLA if it deems the submission incomplete or not properly reviewable at the time of submission.

BLA review process to proceed, the BLA must be resubmitted with the necessary additional information.

After the BLA is accepted

for filing, the FDA commences its substantive review of the BLA.

The FDA reviews the BLA to determine, among other things, whether

the proposed product is safe, potent, and/or effective for its intended use, has an acceptable purity profile, and whether the

product’s manufacturing is consistent with current Good Manufacturing Processes (“cGMPs”) to ensure that the

product meets the appropriate standards for identity, safety, strength, quality, potency and purity.

The FDA may involve an

advisory committee for novel biological products that present complex questions of safety or efficacy.

The advisory committee typically

consists of a panel that includes clinicians and other subject matter experts that assist with the reviewing and evaluating the

While the advisory committee provides a recommendation for whether the product should be approved and under what conditions,

the FDA is not bound to follow the recommendations.

However, the advisory committee’s recommendations are usually given significant

consideration.

The FDA may also consider

requiring a risk evaluation and mitigation strategy (“REMS”) if it determines that one is necessary to ensure that

the biological product is used safely.

If the FDA requires a REMS, the BLA sponsor must develop and submit a proposed REMS for

the BLA review process to move forward.

The manufacturer of the

biological product is also subject to FDA inspection prior to the approval of the BLA.

The purpose of the inspection is to determine

whether the manufacturer adequately complies with the applicable cGMP requirements to ensure that the biological product is manufactured

safely and within the required specifications.

Additionally, the FDA may choose to inspect one or more clinical sites to assess

compliance with IND trial requirements and good clinical practices (“GCPs”).

Compliance with cGMP and GCP requirements

involves significant expenditures of time, money, and effort for BLA sponsors due to associated training, recordkeeping, production,

and quality control needs.

If the FDA decides not

to approve the BLA in the form submitted, it will issue what is called a complete response letter that outlines the specific deficiencies

it would like to see addressed.

The deficiencies identified can be minor (e.g., labeling changes) or major (e.g., the need for

additional clinical trials).

The complete response letter may also include recommended actions the applicant may take to move closer

towards securing an approval.

At this point, applicants may choose to resubmit the BLA to address FDA’s concerns or withdraw

the application.

In addition, under the

Pediatric Research Equity Act, a BLA or supplement to a BLA must contain data to assess the safety and effectiveness of the product

for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric

subpopulation for which the product is safe and effective.

The FDA may grant deferrals for submission of data or full or partial

Post-Approval Requirements

If the BLA is approved,

the FDA may include additional conditions as part of its approval, such as limiting the approval by designating specific diseases

for which the product may be used.

Additionally, conditions may include requiring the labeling to include specific contraindications,

warnings, or precautions, requiring post marketing clinical trials (sometimes referred to as Phase 4 clinical trials), and implementation

of surveillance program to monitor the approved product once commercialized.

Products approved by the

FDA under a BLA are subject to ongoing regulatory requirements, including, among other things, record-keeping requirements, adverse

event reporting requirements, responsibility for reporting updated safety and efficacy information to FDA, sampling and distribution

requirements, complying with advertising and promotion requirements, and complying with cGMPs.

Quality control and manufacturing

procedures must continue to comply with cGMP requirements even after the BLA is approved.

The cGMP regulations include, but are

not limited to, requirements to ensure quality control, maintain appropriate manufacturing records and documentation, and the obligation

to investigate and address deviations from cGMPs, when identified.

Manufacturers are also required to register their establishments

with the FDA and certain state agencies.

The establishments are also subject to unannounced inspections by regulators.

The advertising and promotion

of drug and biologic products are also subject to specific laws and regulations.

These authorities provide standards for direct-to-consumer

advertising, restrictions on promoting products for uses or to patient populations that are not described in the product’s

approved uses, known as “off-label”

use, limitations on industry-sponsored scientific and educational activities, and

requirements for promotional activities involving the internet.

Regulatory Enforcement

Failure to comply with

applicable regulatory requirements can result in enforcement action by the FDA, the Nuclear Regulatory Commission or other regulatory

authorities, which may result in sanctions, including but not limited to, untitled letters, warning letters, fines, injunctions,

consent decrees and civil penalties;

customer notifications or repair, replacement, refunds, recall, detention or seizure of our

operating restrictions or partial suspension or total shutdown of production;

or delaying our requests for BLA premarket approval of new products or modified products;

withdrawing BLA approvals that have

already been granted;

and refusal to grant export.

of May 7, 2020, we have 25 full-time employees.

None of these employees are covered by a collective bargaining agreement, and

we believe our relationship with our employees is good.

We also engage consultants on an as-needed basis to supplement existing

refusing or delaying our requests for BLA

premarket approval of new products or modified products;

withdrawing BLA approvals that have already been granted;

to grant export.

Additional Healthcare Laws

In addition to FDA regulations,

several other types of state and federal laws may restrict our business activities, including certain healthcare laws.

include, without limitation, anti-kickback laws, false claims laws, data privacy and security laws, as well as transparency laws

regarding payments or other items of value provided to healthcare providers.

The federal Anti-Kickback

Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce

or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any healthcare item, good, facility

or service reimbursable under Medicare, Medicaid or other federal healthcare programs.

The term “remuneration”

been broadly interpreted to include anything of value.

This statute has been interpreted to apply to arrangements between pharmaceutical

manufacturers on the one hand and prescribers, purchasers and formulary managers on the other hand.

Although there are a number

of statutory exceptions and regulatory safe harbors protecting certain common activities from prosecution or other regulatory sanctions,

the exceptions and safe harbors are drawn narrowly and arrangements must meet every element to qualify for an exception or safe

Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not

make the conduct per se illegal under the federal Anti-Kickback Statute.

Instead, the arrangement will be evaluated on a

case-by-case basis based on the facts and circumstances involved.

Courts have interpreted the statute’s intent requirement

to mean that if any one purpose of an arrangement involving remuneration is to induce referrals of federal healthcare program business,

the federal Anti-Kickback Statute has been violated.

Additionally, the intent standard under the federal Anti-Kickback Statute

was amended by the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation

Act of 2010, collectively the “Affordable Care Act,”

to a stricter standard such that a person or entity no longer

needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

the Affordable Care Act codified case law that a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent

claim for purposes of the federal False Claims Act.

Federal false claims laws,

including the federal False Claims Act, and civil monetary penalties laws, prohibit any person or entity from, among other things,

knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or

causing to be made, a false statement to have a false claim paid.

Whistleblower or qui tam provisions under the False Claims Act

permit whistleblowers to sue in the name of the federal government for False Claims Act violations, and to share in the recovery

from any award.

Pharmaceutical and other healthcare companies have been prosecuted under these laws for, among other things, allegedly

inflating drug prices they report to pricing services, which in turn were used by the government to set Medicare and Medicaid reimbursement

rates, and for allegedly providing free product to customers with the expectation that the customers would bill federal programs

for the product.

In addition, certain marketing practices, including off-label promotion, may also violate false claims laws.

The federal Health Insurance

Portability and Accountability Act of 1996, or HIPAA, created additional federal civil and criminal statutes that prohibit among

other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program,

including private 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 statement in connection with the delivery of or payment

for healthcare benefits, items or services.

Like the federal Anti-Kickback Statute, the Affordable Care Act amended the intent

standard for certain healthcare fraud under HIPAA such that a person or entity no longer needs to have actual knowledge of the

statute or specific intent to violate it in order to have committed a violation.

In addition, if we engage

in certain activities, we may be subject to data privacy and security regulation under HIPAA, as amended by the Health Information

Technology for Economic and Clinical Health Act, or HITECH.

HIPAA imposes certain requirements on covered entities, which include

certain healthcare providers, health plans and healthcare clearinghouses, and their business associates and covered subcontractors

that receive or obtain protected health information in connection with providing a service on behalf of a covered entity that involves

the use or disclosure of individually identifiable health information.

Additionally, the federal

Physician Payments Sunshine Act, created under the Affordable Care Act, and its implementing regulations, require certain manufacturers

of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s

Health Insurance Program (with certain exceptions) to report annually information related to certain payments or other transfers

of value provided to physicians and any ownership and investment interests held by physicians or their immediate family members.

Beginning in 2022, applicable manufacturers also will be required to report such information regarding payments and other transfers

of value to physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified registered

nurse anesthetists and certified nurse midwives during the previous year.

The majority of states

also have statutes or regulations similar to the aforementioned federal healthcare laws, including fraud and abuse laws, some of

which are broader in scope and apply to items and services reimbursed under Medicaid and other state programs, or, in some states,

apply regardless of the payor.

Many states also have some form of health information privacy or data security laws that could apply.

Further, some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance

guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers

to report information related to payments or other transfers of value provided to physicians and other healthcare providers and

entities, marketing expenditures, or drug pricing.

Certain state and local laws also require the registration of pharmaceutical

sales representatives.

If our operations are found

to be in violation of any of the healthcare regulatory laws described above or any other laws that apply to us, we may be subject

to potentially significant criminal, civil and administrative penalties, damages, fines, disgorgement, imprisonment, additional

reporting obligations and oversight (if we become subject to a corporate integrity agreement or other agreement to resolve allegations

of non-compliance with these laws), exclusion from participation in government healthcare programs, as well as contractual damages,

reputational harm, administrative burdens, diminished profits and future earnings, and the curtailment or restructuring of our

operations, any of which could adversely affect our ability to operate our business and our results of operations.

As of March 31, 2021, we have 32 full-time employees

including 13 with M.D., Ph.D.

or other advanced degrees.

We believe that our future

success largely depends upon our continued ability to attract and retain highly skilled employees.

We provide our employees with

competitive salaries and bonuses, opportunity for equity ownership, development programs that enable continued learning and growth,

and a robust employment package that promotes wellness across all aspects of their lives, including healthcare, retirement planning,

and paid time off.

None of these employees are covered by a collective bargaining agreement, and we believe our relationship with

our employees is good.

We also engage consultants on an as-needed basis to supplement existing staff.

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