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Item 1. Business

2022-03-25 compared with 2021-03-31 · 767 added, 580 removed, 52 unchanged (96% of the section changed)

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

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 radiotherapies for patients with unmet needs.

Our targeted radiotherapies combine 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.

They also 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, which generally cannot be treated with external radiation given their diffuse nature.

Our clinical pipeline is focused

on targeting the antigens CD45 and CD33, both of which are expressed in multiple hematologic cancers, which are known to be highly sensitive

to radiation.

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”).

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

adoptive cell therapy (“ACT”) such as CAR-T or gene therapy with Iomab-B and (2) targeted radiotherapy combinations with Actimab-A

and other therapeutic agents.

Our product development strategy is actively informed by clinical data with Iomab-B and Actimab-A in approximately

600 patients, including our ongoing Pivotal Phase 3 SIERRA trial, which completed its targeted enrollment of 150 patients in the third

quarter of 2021, with the last patient receiving their BMT in the fourth quarter of 2021.

Our clinical pipeline has emanated from our

Antibody Warhead Enabling (“AWE”) technology platform, which is protected by over 170 issued and pending patents, trade secrets

and know-how that we are applying to the development of targeted radiotherapies for blood and solid tumor indications, independently and

with collaborators.

Ongoing collaborations include a research partnership with Astellas Pharma, Inc.

(“Astellas”) focused

on the development of theranostics, which enable the diagnosis and treatment, for solid tumor indications, a collaboration with EpicentRx,

Inc, focused on a novel CD47 immunotherapy targeted radiotherapy combination, leveraging EpicentRx’s RRx-01, that is being studied

in a Phase 3 trial in non-small cell lung cancer, with our clinical stage Actimab-A in AML models, and a collaboration with AVEO Oncology,

focused on developing a HER3 targeting ARC or Antibody Radiation Conjugate for solid tumors leveraging with their clinical stage antibody.

We are also utilizing our AWE technology platform to advance our research objectives focused on developing next-generation targeted radiotherapies

with our expanded research and development organization and research laboratories leveraging our drug development experience.

Targeted Conditioning

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, cancer cells prior to transplanting new cells into a patient.

Currently, conditioning is accomplished

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, 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.

To the best of our knowledge, we are advancing the only multi-target, multi-indication, clinical-stage pipeline for targeted conditioning.

Our targeted conditioning agents are intended to potentially enable improved access and outcomes to cell-based therapies with curative

potential, including BMT, ACT, and gene therapy Conditioning 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, cancer cells prior to transplanting new cells into

Currently, conditioning is accomplished using a combination of cytotoxic chemotherapeutic agents and external radiation.

non-targeted conditioning regimens are highly toxic and may prevent a patient from receiving a potentially curative therapy and hinder

We believe our targeted conditioning agents have the potential to increase 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 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.

Iomab-B (I-131 apamistamab),

our lead candidate and targeted conditioning agent 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,

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 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 (“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”).

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.

Iomab-B uses high doses of

I-131 to achieve myeloablative conditioning prior to a BMT, 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.

Enrollment of

the planned 150 patients in the SIERRA trial was completed in the third quarter of 2021 with the last patient receiving their BMT in the

fourth quarter of 2021.

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

therapy (the “control arm”).

The control 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 Remission (“CR”) 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 (“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 recruited patients at 24 sites in the United States and Canada, which

includes many of the leading BMT sites based on volume.

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

as having failed the primary endpoint of the study.

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

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 believe our Iomab-ACT

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.

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.

Data from full patient enrollment in the SIERRA trial (151 patients), was presented at the American Society of Hematology (“ASH”)

Annual Meeting in December 2021.

The data presented includes rates of BMT access and engraftment, 100-day non-relapse transplant-related

mortality (100-day TRM) and adverse events, which has been reported from interim analyses conducted at 25%, 50% 75% and 100% of patient

enrollment pursuant to the study protocol.

The data presented at ASH highlighted that 100% of patients (59/59) 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 17% of patients (13/76) 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 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 as having failed the primary endpoint of the study.

All crossover patients who received the

therapeutic dose of Iomab-B (30/30) 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 TRM of the study or Iomab-B

arm was 10% (6/59) of patients that received a BMT compared to 15% of patients (2/13) who received a BMT after salvage therapy on the

The universal engraftment rate and low 100-day TRM rate of the Iomab-B arm resulted in 53 patients potentially evaluable

for the primary endpoint compared to 11 patients in the control arm, an approximate five times difference.

At each of the interim analyses

throughout the SIERRA trial, this approximate five times difference has been consistent in favor of the Iomab-B arm as a result of higher

rates of BMT engraftment and lower rates of 100-day TRM.

Data from the SIERRA trial has

also been accepted for presentation at the upcoming Transplantation & Cellular Therapy (“TCT”) Tandem Meetings of the

American Society for Transplantation and Cellular Therapy (“ASTCT”) and Center for International Bone & Marrow Transplant

Research (“CIBMTR”), which has been postponed from February to April 2022.

At TCT, we expect to present additional data from

the SIERRA trial to include patients who have matured for BMT engraftment and 100-day TRM analysis, for which data was not available at

time of the submission cutoff for ASH in December of 2021.

Top-line data for the primary endpoint of durable Complete Remission is expected

to be presented in the third quarter of 2022.

We believe topline data from SIERRA will support the submission of a Biologics License Application

(“BLA”) with the U.S.

Food and Drug Administration (“FDA”), which we expect to file in the first half of 2023.

Our Iomab-ACT program is intended

for targeted conditioning prior to ACT or gene therapy and uses the same I-131-apamistamab construct as Iomab-B at varying doses.

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 believe our Iomab-ACT 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

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.

of this potentially superior profile, the Iomab-ACT construct could result in improved access to CAR-T therapy and better outcomes.

We are studying Iomab-ACT in a

clinical collaboration with Memorial Sloan Kettering Cancer Center (“MSKCC”) 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.

This is a first of its kind study to use an ARC-based conditioning regimen

with CAR-T therapy.

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 1 – 65 months).

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.

In March 2021, we announced that patient enrollment was initiated, and the first patient was administered Iomab-ACT followed by their

19-28z CAR-T therapy.

We expect proof of concept data from this study in the second half of 2022.

In addition, we are working

in collaboration with the University of California Davis to utilize Iomab-ACT conditioning with a novel anti-HIV autologous gene therapy.

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.

CD33 Program:

Combinations Trials and Targeted

Combinations and Therapeutics

Our CD33 program is evaluating

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.

the clinical utility of Actimab-A, 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 (“MDS”) as well

as approximately one-third of patients with multiple myeloma.

Ac-225 emits four alpha particles and can kill a cell with one alpha-particle

hit, making it one of the most powerful cell-killing agents with no know resistance mechanism to the double strand DNA breaks it can cause.

We source Ac-225 from the Department of Energy’s Oak Ridge National Laboratory.

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 studied Actimab-A

as a single agent at multiple dose levels in 58 patients with newly diagnosed AML, which was completed in 2018, as well as trials studying

Actimab-A in combination with other agents.

We believe that radiation delivered

internally via a targeting moiety 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.

We 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 as we believe Actimab-A can be a backbone therapy in AML when combined with other therapeutic modalities.

CD33 development program encompasses the following ongoing trials:

Actimab -A Combination Trials :

Actimab-A + CLAG-M

The combination of Actimab-A with CLAG-M has been

studied in a Phase 1 combination trial that was conducted in collaboration with the Medical College of Wisconsin (“MCW”) in

patients age 18 and above with r/r AML who are fit for intensive therapy.

Patient enrollment was completed in November 2021.

CLAG-M (cladribine,

cytarabine, filgrastim and mitoxantrone) is a salvage chemotherapy regimen that produced a 55% remission rate in patients with r/r AML

in a previous study conducted by MCW that compared outcomes of patients receiving either CLAG-M, MEC or CLAG salvage therapy regimens.

Data from the Phase 1 combination trial of Actimab-A + CLAG-M were presented at ASH in December 2021.

After completion of dose-escalation

in the Phase 1 trial, the recommended Phase 2 dose was determined to be 0.75 µCi/kg of Actimab-A.

3 patients were enrolled in the

0.75 µCi/kg dose cohort, which had a 100% remission rate comprised of 1 complete remission (“CR”) and 2 complete remissions

with incomplete platelet recovery (“CRp”), there were no dose limiting toxicities (“DLTs”) or 30-day mortality

Overall, a 67% (12/18) overall response rate (“ORR”) was reported across all dose cohorts (0.25 – 1.0 µCi/kg)

and remissions were achieved in every dose cohort including the 0.25 and 0.50 µCi/kg doses of Actimab-A, which have been shown to

be subtherapeutic as a single agent.

In addition, there was a 72% minimal residual disease (“MRD”) negativity rate, which

compares favorably to the 39% MRD negativity rate reported by MCW with CLAG-M alone.

This study enrolled patients who previously failed

Venetoclax, a targeted Bcl-2 inhibitor, and efficacy was similar in patients Venetoclax naïve and those that previously failed Venetoclax,

with a 60% response rate in previous Venetoclax failures.

We are working to develop a regulatory and development pathway for the Actimab-A

CLAG-M combination and will be evaluating potential registration enabling strategies.

In addition, we believe this Actimab-A + CLAG-M

combination study has provided proof of principle that the addition of Actimab-A to other AML therapies can lead to well-tolerated regimens

with improved responses, which supports our Actimab-A backbone therapy in AML strategy.

Actimab-A + Venetoclax

We are also conducting a Phase

1/2 Actimab-A combination trial with the Bcl-2 inhibitor Venetoclax in fit and unfit patients age 18 and above with relapsed or refractory

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.

However, dose-dependent myelosuppression, a class effect of CD33 directed therapies, was seen in many

of these patients.

Given that myelosuppression is necessary prior to a BMT and that a BMT can rescue patients with myelosuppression,

we decided to pursue a trial in targeted conditioning in high-risk MDS patients with this ARC in combination with Reduced Intensity

Conditioning, or RIC, regimens.

RIC regimens are comprised of low doses of chemotherapies such as fludarabine, cytarabine, busulfan

or melphalan.

A BMT is the only curative treatment option for these patients with high-risk MDS who have poor, or very poor cytogenetics.

However, these patients have poor outcomes due to high relapse rates following a BMT.

Based on our interactions with FDA to date,

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.

This combination is supported by mechanistic evidence in preclinical

studies using Venetoclax -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 Venetoclax-resistant AML demonstrated robust tumor regression

and improved survival in cohorts receiving the Actimab-A Venetoclax combination compared to Venetoclax 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 Venetoclax.

Updated data from the Phase 1 dose escalation portion of this study was presented

at ASH in December 2021 from three dose cohorts of 0.50, 0.75 and 1.0 µCi/kg of Actimab-A in a total of 12 patients.

50% of patients

received Venetoclax therapy prior to enrollment on the Actimab-A combination trial.

And 67% of patients had poor risk cytogenetics, of

which, 3 had a TP53 mutation, which is associate with poorer response rates and survival outcomes.

Of the patients with a TP53 mutation,

67% achieved a remission including a patient that achieved a CR and at the time of data cutoff for ASH, the patient was in follow-up 230

days (~7.5 months).

The combination of Actimab-A with Venetoclax was reported to be well-tolerated with no 30-day mortality.

to date support advancing to the Phase 2 portion of the trial and we expect to provide an update on the development strategy, including

consideration of patients with a TP53 mutation, after the Phase 1 dose finding portion of the trial is complete and the recommended Phase

2 dose is determined.

In addition to these ongoing

trials, we actively seek and evaluate additional modalities and agents that can be the basis for Actimab-A therapeutic combinations such

as the CD47 immunotherapy magrolimab combinations we announced at the Society for Immunotherapy of Cancer in November 2021 to leverage

our clinical experience, supply chain and AWE technology platform.

CD47 Based ARC Combinations in Solid Tumors

and Blood Cancers

CD47 is a macrophage checkpoint

that is upregulated in multiple cancers including blood cancers such as AML and MDS as well as solid tumors.

CD47 acts as a “don’t

eat me” signal on cancer cells to suppress phagocytosis and evade detection and destruction by the immune system.

It has become

an immunotherapy target of significant interest with multiple biopharmaceutical companies actively developing CD47 targeting agents across

a wide range of oncology and hematology indications.

CD47 targeting agents have shown limited efficacy as single agent monotherapies in

AML/MDS or solid tumors, which has led to combinations such as with hypomethylating agents in AML/MDS.

We hypothesized that targeted radiotherapy

via ARCs could synergize with CD47 targeting agents via the direct cytotoxic and immunogenic effect of ARCs without overlapping toxicities.

To explore this synergy and the potential to improve patient outcomes and we have initiated a program in AML with our Actimab-A ARC, consistent

with our strategy to establish Actimab-A a backbone AML therapy, and in solid tumors with a HER-2 targeting ARC, which emanated from our

AWE technology platform.

To our knowledge, these are the first and only ARC-based targeted radiotherapy combinations with CD47 immunotherapy.

Data from these novel combinations were presented at the 36 th Annual Meeting of the Society for Immunotherapy for Cancer.

The most advanced CD47 development

programs are being studied in patients with AML and MDS.

Leveraging our clinical experience with Actimab-A in these indications we have

begun studying Actimab-A with the anti-CD47 antibody immunotherapy magrolimab, which is owned by Gilead Sciences, Inc., in preclinical

models of AML.

In preclinical models, it was shown that in multiple AML cell lines, the combination of Actimab-A with magrolimab led to

increased phagocytosis of AML cells compared to magrolimab alone.

Our studies also demonstrated that AML cell lines exposed to Actimab-A

had an upregulation of calreticulin, which is a pro-phagocytic or “eat me” signal, which we hypothesize makes Actimab-A potentially

synergistic with magrolimab and other anti-CD47 antibodies.

The Actimab-A and magrolimab combination showed a significant increase in

survival compared to Actimab-A alone in a disseminated AML animal tumor model.

We intend to continue to study preclinically this combination

with the goal of advancing to human clinical trials.

In January 2022, we announced

a research collaboration with EpicentRx that will evaluate Actimab-A in combination with EpicentRx’s RRx-001in AML.

RRx-001, currently under investigation in a Phase 3 trial for Small Cell Lung Cancer and in other oncology and non-oncology indications,

is a versatile next generation small molecule immunotherapeutic that targets the CD47-SIRPα axis and the NLRP3 inflammasome to

alter the tumor microenvironment and optimize immune response.

This collaboration will explore the mechanistic synergy of RRx-001’s

CD47–SIRPα downregulation with Actinium’s targeted radiotherapy calreticulin upregulation to increase the immune detection

and destruction of cancer cells.

Preclinical experiments have begun exploring this combination in AML models.

We intend to leverage our

experience with CD47 targeting agents such as magrolimab in this collaboration.

Based on Actimab-A and RRx-001 both being clinical-stage

assets, we believe there is a potentially faster pathway to clinical trials with this novel combination, particularly if the preclinical

safety and efficacy profile are in line with what was observed with Actimab-A and magrolimab.

Antibody Warhead Enabling Technology Platform

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.

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

manufacture of targeted radiotherapies and certain of their components.

Our AWE technology patent portfolio presently includes 39 patent

families comprised of 173 issued patents and pending patent applications, of which 8 are issued and 30 are pending in the United States,

and 135 are issued or pending internationally.

The effective lives of the issued patents in our portfolio, or patents that may issue from

the pending applications in our portfolio, ranges from expirations between 2024 and 2042.

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 in multiple diseases,

including indication, dose and scheduling, radionuclide warhead, and therapeutic combinations.

We have particular expertise in utilizing

the alpha emitting isotope Ac-225 including clinical experience in treating approximately 150 patients with our alpha-emitter-based therapies,

“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 than currently utilized

In 2021 we have enhanced our

research and development capabilities around AWE by securing and staffing research facilities.

Our research laboratories are focused on

applying our AWE technology platform to the development of radiation conjugates and to execute on research collaborations.

efforts employ a multidisciplinary approach leveraging our team’s knowledge and experience in cancer cell biology, radiochemistry,

radiation sciences, immunology and oncology drug development.

We intend to focus on generating targeted radiotherapies using our existing

intellectual property, evaluating assets for in-licensing to complement our existing clinical pipeline and securing collaborations and

partnerships with biopharmaceutical companies.

By adding research and development capabilities to our clinical development and clinical

supply chain capabilities, we seek to enable the rapid translation of radiotherapies.

Our AWE technology platform

is being utilized in our ongoing research collaboration with Astellas to arm select targeting agents owned by Astellas with the alpha-emitting

radioisotope Ac-225 for the development of theranostics for solid tumor indications, which combine the ability of radioisotopes to be

used for both diagnostic and therapeutic purposes.

We also utilized AWE to create aHER2-targeting radiotherapy using

the antibody Trastuzumab with either Ac-225 or Lu-177 radioisotopes to study in combination with magrolimab for solid tumors.

monotherapies, such as magrolimab, have not shown meaningful responses in clinical studies in solid tumors.

We hypothesized that radiation

directed at HER2 expressing cells would upregulate cell surface calreticulin, a pro-phagocytic “eat me” signal, that when

combined with an anti-CD47 blockade therapy would enhance antitumor activity.

Data from this combination was presented at the Annual Meeting

of the Society for Immunotherapy for Cancer in November 2021.

In vitro studies showed that immunogenicity, determined by binding to HER2

expressing cells, remained intact after radiolabeling Trastuzumab with Ac-225 or Lu-177.

In multiple cells lines radiolabeled Trastuzumab

increased cell surface calreticulin and the combination with magrolimab increased phagocytosis.

The combination of the Ac-225 or Lu-117

Trastuzumab with magrolimab slowed tumor growth in animal models of solid tumors compared to either the radiolabeled Trastuzumab or magrolimab

as single agents.

We are continuing to evaluate this combination in additional tumor models, and we intend to continue to study this combination

with the goal of advancing to human clinical trials.

We are also collaborating

with AVEO Oncology (“AVEO”) to develop a targeted radiotherapy against ErbB3, also known as HER3, with the Ac-225 isotope

for solid tumor indications.

HER3 is overexpressed in several solid tumor indications with high unmet needs, including colorectal, gastric,

head and neck, breast, ovarian, melanoma, prostate and bladder cancers with HER3 agents under development demonstrating activity in preclinical

and clinical studies.

To our knowledge, this is the first HER3 targeting radiotherapy in development.

AVEO is developing high affinity

antibodies including HER3 targeting AV-203, which has demonstrated preclinical activity across a number of solid tumor indications and

was studied in a Phase 1 open-label trial in patients with advanced solid tumors where it was found to be safe and generally well tolerated.

In March 2022, we announced that data from studies of Ac-225 radiolabeled HER3 antibody have been accepted for presentation at the American

Association for Cancer Research (“AACR”) Annual Meeting.

Preliminary results contained in the AACR abstract showed potent

tumor cell cytotoxicity, complete anti-tumor response in a HER3 tumor xenograft models and significantly prolonged survival compared to

control groups (p<0.0001).

Additional data from these studies will be presented at AACR in April 2022.

We believe these preliminary

results support our collaboration with AVEO and given that AV-203 has clinical safety data, a potentially accelerated regulatory pathway

to clinical studies with an Ac-225 HER3 targeted radiotherapy.

Intellectual Property Portfolio and Regulatory Protections

3 unchanged sentences

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

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.

As of March 2022, our patent portfolio includes 39 patent families comprised of 174 issued patents and pending patent

applications, of which 8 are issued and 30 are pending in the United States, and 135 are issued or pending internationally.

Several non-provisional

patent applications are expected to be filed in 2022 based on provisional patent applications filed in 2021.

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 the

use of actinium-225 and other alpha- or beta-emitting isotopes attached to cancer targeting carriers like monoclonal antibodies in the

treatment of cancers and non-malignant medical disorders, 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 two issued patents

in the United States and issued patents in Europe and Japan that relate to the composition of our Iomab-B product candidate.

patent terms of these patents expire in 2036 and 2037.

Four related patent applications are also currently pending in the U.S.

and internationally.

In addition, we own both U.S.

and international pending patent applications that relate to the use of Iomab-B or Iomab-ACT in the treatment

of cancers and non-malignant conditions.

We also own five issued patents in the United States and 49 patents outside the United States

that relate to the manufacturing of actinium-225, the radionuclide used in our Actimab-A product candidate, in a cyclotron.

patents will expire in the years 2024 through 2027.

In addition, we also own U.S.

and international patents and pending patent applications

that relate to the manufacturing of Actimab-A and its use in the treatment of cancers.

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.

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 Actimab-A

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.

In addition, our product candidates are biologics combined

with radioisotopes.

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.

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.

However, we are not aware

of any existing or pending regulations or legislation that pertains to generic radiopharmaceutical products such as our antibody radiation-conjugate

product candidates

The biopharmaceutical industry

in which we operate, specifically, the field of oncology drug development is rapidly evolving and highly competitive.

Radiopharmaceuticals

for the treatment of cancer has received considerable interest from major and specialty pharmaceutical companies, biotechnology companies,

academic research institutions and other public and private entities, particularly in recent years.

For the targeted radiotherapies

we are developing, we face competition from biopharmaceuticals companies who are developing alpha particle-based therapies utilizing Actinium-225,

Radium-223 and Thorium-227.

Companies developing targeted alpha therapies include Bayer AG, who owns Xofigo, the only approved alpha therapy,

that is used in the treatment of metastatic prostate cancer, Novartis AG, Telix Pharmaceuticals Limited, Point Biopharma, Inc., Fusion

Pharmaceuticals, Inc., RayzeBio, Inc., Aktis Oncology, Curie Therapeutics, RadioMedix, Inc.

and Orano Med.

Significant attention and resources

is being applied to Ac-225 based therapies given its high linear energy and short path length.

Fusion Pharmaceuticals is studying FPI-1434,

targeting IFG-1R with Ac-225 in a Phase 1 trial in solid tumors and has recently initiated a Phase 1 study to test FGFR3 targeting agent

in development.

Point Biopharma is studying PNT2002, a PSMA targeting agent for metastatic prostate cancer in a Phase 1 trial, PNT2004,

a preclinical agent targeting solid tumors expressing FAP, and PNT2001, a preclinical agent also targeting PSMA in prostate cancer, which

all utilize Ac-225.

Novartis is also developing a PSMA targeting agent utilizing Ac-225 for prostate cancer.

RayzeBio, Aktis Oncology

and Curie Therapeutics are all pursuing Ac-225 based therapies but have not yet disclosed cancer targets or indications.

To our knowledge, our Actimab-A

product candidate is the only clinical stage Ac-225 based therapy in active development for hematologic indications.

There are also several companies

developing beta particle-based therapies such as Bayer, Novartis, Lantheus Holdings, Inc.

and Q BioMed, Inc., who all own approved products.

Beta particles used for oncology therapeutics includes Iodine-131, Lutetium-177, Strontium-89 and Yttrium-90.

Companies developing beta

particle-based therapies includes Cellectar Biosciences, Inc., Clovis Oncology, Inc., Y-mAbs Therapeutics, Inc., Ipsen S.A., and Novartis.

In the field of conditioning,

pharmaceuticals currently used for myeloablation prior to a bone marrow transplant, lymphodepletion prior to CAR-T and other adoptive

cell therapies and conditioning for gene therapy are largely generic, non-targeted chemotherapeutic agents like fludarabine or busulfan

and/or total body irradiation.

In targeted conditioning,

we face competition from companies developing agents targeting CD117 (Jasper Therapeutics and Magenta Therapeutics), CD45 (Magenta Therapeutics)

and CD66 (Telix Pharmaceuticals).

CD117 is expressed in normal CNS, GI, reproductive, kidney and skin tissue, which could result in on-target

toxicity to these organs.

CD117 is not expressed on mature circulating immune cells and thus cannot be targeted for lymphodepletion for

adoptive cell therapy.

Jasper Therapeutics, Inc, is developing JSP191, an anti-CD117 unconjugated monoclonal antibody that is being studied

in a Phase 1b trial in combination with fludarabine and total body irradiation in patients with MDS and AML.

Magenta has initiated a Phase

1/2 trial for its MGTA-117 CD117 ADC and will conduct this first in human dose finding study in patients with r/r AML MDS with excess

blasts and is exploring MGTA-117 for gene therapy conditioning in preclinical studies.

Magenta is also developing its CD45 ADC, which

is has not yet been studied in humans and is being evaluated in IND enabling studies.

Forty Seven, Inc.(acquired

by Gilead) announced a conditioning regimen comprised of its anti-CD47 monoclonal antibody Magrolimab with its preclinical stage FSI-174

anti-CD117 monoclonal antibody in a preclinical collaboration with bluebird bio, Inc.

for conditioning prior to gene therapy.

Molecular Templates announced

a collaboration with Vertex focused on targeted conditioning using its Engineered Toxin Bodies (ETBs) with two targets that were not disclosed.

In October 2021, Vertex terminated the research collaboration with Molecular Templates.

Molecular Templates has a preclinical stage CD45

ETB in development.

Telix Pharmaceuticals is developing

TLX66, a CD66 targeting antibody radio conjugated with Yttrium-90, for BMT conditioning in patients with Systemic Amyloid Light-Chain

Amyloidosis (SALA).

TLX66 is also being studied in a Phase 2 investigator sponsored trial in the U.K in patients with childhood leukemia.

Allogene Therapeutics is developing

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

CD52 is not expressed on stem

cells and therefore cannot be used for myeloablation for a bone marrow transplant.

To our knowledge, we are the

only company with an anti-CD45 radio conjugate in clinical development and the only company with a targeted conditioning agent that has

completed enrollment of a pivotal Phase 3 trial.

Our Actimab-A product candidate

faces competition from several major pharmaceutical companies and biotechnology companies who are also developing multiple types of therapies

including chemotherapy, targeted agents, ADCs, monoclonal antibodies, bispecific antibodies, immunotherapies and cellular therapies for

patients with AML.

The standard of care for patients with AML has long been “7+3”, which is 7 days of treatment with cytarabine

with an anthracycline on the first 3 days for patients who can tolerate intensive therapy and hypomethylating agents, azacitidine or decitabine,

for patients who are “unfit” and cannot tolerate intensive therapy.

Since 2017, 9 agents have been approved for patients with

These approved agents include Vyxeos (liposomal cytarabine and daunorubicin) owned by Jazz Pharmaceuticals, venetoclax, a Bcl-2 inhibitor

owned by Abbvie, FLT3 inhibitors midostaurin (owned by Novartis) and gilteritinib (owned by Astellas), Daurismo, a hedgehog pathway inhibitor

owned by Pfizer, IDH inhibitors Tibsovo (IDH1) and Idhifa (IDH2) owned by Servier, Onureg (oral azacitidine) owned by Bristol Myers Squibb

and Mylotarg, a CD33 targeting ADC owned by Pfizer.

These agents are approved in

various AML patient segments including secondary or treatment related AML (Vyxeos), patients over the age of 75 or patients unfit for

intensive therapy (venetoclax and Daurismo) and patients with a specific cytogenetic mutation such as FLT3 or IDH1/2.

Despite these 9

approved agents, outcomes for patients with r/r AML remain dismal and it remains an area of high medical need that could accommodate many

new products with favorable safety and efficiency profiles.

We are pursuing CD33 because

it is expressed in virtually all patients with AML.

AML is known to be highly sensitive to radiation, which lends itself to our targeted

radiotherapy approach.

Also, AML has high cytogenetic and mutational heterogeneity, which targeted radiotherapy is agnostic to.

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

is being explored in hematologic indications in combination with other modalities, including 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.

In addition to developing

targeted radiotherapies, we also own patents related to the manufacturing of Ac-225 in a cyclotron.

Medical grade Ac-225 is largely supplied

Department of Energy (“DOE”) derived from the natural decay of thorium-229 from so-called “thorium-cows”.

Additional routes of Ac-225 production are being pursued by the DOE including the generation of new thorium cows and production via a

cyclotron to increase supply.

The DOE’s cyclotron production method for Ac-225 production leverages Actinium’s proprietary

technology and know-how and presents an additional path towards production of high-quality Ac-225.

Previously, we utilized our cyclotron

production IP to create highly pure Ac-225.

We are aware of at least six other government and non-government entities globally that have

or expect to have ability to supply Ac-225 using various methods including ITM, Niowave, Terrapower, NorthStar Medical Radioisotopes,

IONETIX Corporation, TRIUMF and Canadian Nuclear Laboratories that could be competitors should we elect to manufacture Ac-225 in the future.

We believe our cyclotron method has the potential to produce robust amounts of highly pure Ac-225, which could address potential future

Ac-225 supply constraints should multiple Ac-225 products gain regulatory approval.

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

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

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.

Food and Drug Administration Regulation

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

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 will require FDA approval of a BLA prior to marketing.

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

Foreign countries may require

similar or more onerous approvals to manufacture or market these products.

FDA Approval Process for Biologics License

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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 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.

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 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.

The FDA may refuse to file

the BLA if it deems the submission incomplete or not properly reviewable at the time of submission.

For the 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 product.

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

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

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

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 waivers.

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.

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 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.

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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.

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;

refusing or delaying our requests for BLA

premarket approval of new products or modified products;

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 products;

operating restrictions

or partial suspension or total shutdown of production;

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.

and refusal to grant export.

Additional Healthcare Laws

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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.

These 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.

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” has 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 harbor.

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.

In addition, 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.

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.

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

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.

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.

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.

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

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.

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 25, 2022, we have

32 full-time employees including 20 with M.D., Ph.D.

or other advanced degrees.

1 unchanged sentence

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.

We provide our employees with competitive

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

package that promotes wellness across all aspects of their lives, including healthcare, retirement planning, and paid time off.

these employees are covered by a collective bargaining agreement, and we believe our relationship with our employees is good.

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

Recent Developments

Impact of COVID–19 Pandemic

The global health crisis

caused by the novel coronavirus COVID-19 pandemic and its resurgences has and may continue to negatively impact global economic activity,

which, despite progress in vaccination efforts, remains uncertain and cannot be predicted with confidence.

In addition, the Omicron variant

of COVID-19, which appears to be the most transmissible variant to date, has spread globally.

The full impact of the Omicron variant,

or any subsequent variant, cannot be predicted at this time, and could depend on numerous factors, including vaccination rates among

the population, the effectiveness of COVID-19 vaccines against the Omicron variant and the response by governmental bodies and regulators.

Given the ongoing and dynamic nature of the circumstances, it is difficult to predict the impact of the COVID-19 pandemic on our business.

Many countries around the

world have continued to impose quarantines and restrictions on travel and mass gatherings to slow the spread of the virus.

our ability to continue to operate our business may also be limited.

Such events may result in a period of business, supply and drug

product manufacturing disruption, and in reduced operations, any of which could materially affect our business, financial condition and

results of operations.

In response to COVID-19, we implemented remote working and thus far have not experienced a significant disruption

or delay in our operations as it relates to the clinical development of our drug candidates.

Such government-imposed precautionary measures

may have been relaxed in certain countries or states, but there is no assurance that more strict measures will be put in place again

due to a resurgence in COVID-19 cases, including those involving new variants of the coronavirus, which may be more contagious and deadly

than prior strains.

Therefore, the COVID-19 pandemic may continue to affect our operation, may further divert the attention and efforts

of the medical community to coping with COVID-19 and disrupt the marketplace in which we operate and may have a material adverse effect

on our operations.

A continuation or worsening

of the levels of market disruption and volatility seen in the recent past could have an adverse effect on our ability to access capital,

which could in the future negatively affect our liquidity.

In addition, a recession or market correction resulting from the spread of

COVID-19 could materially affect our business and the value of our common stock.

We believe our earlier stage

CD33 clinical trials will continue to recruit and enroll patients given the acute nature of relapsed or refractory AML.

The continuation

of the pandemic could adversely affect our planned clinical trial operations, including our ability to conduct the trials on the expected

timelines and recruit and retain patients and principal investigators and site staff who, as healthcare providers, may have heightened

exposure to COVID-19 if their geography is impacted by the pandemic.

Further, the continuation and/or resurgence of the COVID-19 pandemic

could result in delays in our clinical trials due to prioritization of hospital resources toward the pandemic, restrictions in travel,

potential unwillingness of patients to enroll in trials at this time, or the inability of patients to comply with clinical trial protocols

if quarantines or travel restrictions impede patient movement or interrupt healthcare services.

In addition, we rely on independent clinical

investigators, contract research organizations and other third-party service providers to assist us in managing, monitoring and otherwise

carrying out our preclinical studies and clinical trials, and the pandemic may affect their ability to devote sufficient time and resources

to our programs or to travel to sites to perform work for us, which may result in delays or hinder our ability to collect data from our

clinical trials.

Additionally, COVID-19 may

result in delays in receiving approvals from local and foreign regulatory authorities, delays in necessary interactions with IRB’s

or Institutional Review Boards, local and foreign regulators, ethics committees and other important agencies and contractors due to limitations

in employee resources or forced furlough of government employees.

To date, COVID-19 has not

had a financial impact on our company.

We continue to monitor the impacts of COVID-19 on the global economy and on our business operations.

Although we expect that vaccinations for COVID-19 will continue to improve conditions, the ultimate impact from COVID-19 on our business

operations and financial results during 2022 will depend on, among other things, the ultimate severity and scope of the pandemic, including

the new variants of the virus, the pace at which governmental and private travel restrictions and public concerns about public gatherings

will ease, the rate at which historically large increases in unemployment rates will decrease, if at all, and whether, and the speed with

which the economy recovers.

We are not able to fully quantify the impact that these factors will have on our financial results during

2022 and beyond.

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