Actinium Pharmaceuticals, Inc. (delaware)AMEX: ATNM

Actimab-A, a CD33-Targeted Actinium-225 Radioconjugate, Drives Mutation-Agnostic Anti-Leukemic Activity and Synergizes with Standard Therapies in AML Through Transcriptional Reprogramming

Apr 22, 2026 at 12:34 AM UTC · Issued by Actinium Pharmaceuticals, Inc. (delaware)

‌Actimab-A, a CD33-Targeted Actinium-225 Radioconjugate, Drives Mutation-Agnostic Anti-Leukemic Activity and Synergizes with Standard Therapies in AML Through Transcriptional Reprogramming‌ Amanda S. Chin1, Merve Sahin2, Jason Li1, Sumit Mukherjee1, Karina Peregrina1, Debbie Lewis1, Kaitlyn H. Ko2, Monideepa Roy1, Wenbin Xiao2, Shiva Kazerounian1, Adeela Kamal1, Sheng F. Cai2 1 Actinium Pharmaceuticals, Inc. New York, NY; 2 Memorial Sloan Kettering Cancer Center New York, NY, USA

Tumor Volume

MV-4-11

Tumor Volume

MV-4-11

2500

3000

Vehicle (PBS)

1500

2000

IgG-Ac225 (0.2 μCi)

Lint-Ac255 (0.2 μCi)

Vehicle (PBS)

IgG-Ac225 (0.2 μCi)

Lint-Ac225 (0.2 μCi)

Gilteritinib (3 mg/kg) Combination

Tumor Volume

OCI-AML3

Vehicle (PBS)

IgG-Ac225 (0.2 μCi)

2000

Lint-Ac225 (0.2 μCi)

Revumenib (25 mg/kg)

1500

Revumenib (25 mg/kg)

1000

Combination

✱✱

Combination

✱✱✱

1000

500

✱✱ ✱✱✱

Days Post Tumor Implant

Days Post Tumor Implantation

2000

Tumor Volume

HL-60

Survival

HL-60

1500

100

1000

✱

✱✱✱✱

***

500

5 10

15 20

Lint-Ac225 Dose

Days Post Treatment

Azacitidine Dose

Days Post Treatment

Lintuzumab-Ac225 potentiates cell death in tumor-bearing mouse models of AML when combined with revumenib, gilteritinib, and azacitidine.

Combination of Lintuzumab-Ac225 with SOC Inhibitors Potentiates In Vivo AML Cell Death Independent of Mutations

Combination vs Gilteritinib alone Combination vs Revumenib alone Combination vs Revumenib alone

Combination vs Azacitidine alone

MV-4-11 MV-4-11 OCI-AML3 HL60

P53 Pathway

Glycolysis MTORC1 Signaling G2M Checkpoint

setSize

≤ 150.00

171.03

P53 Pathway

setSize

147.00

169.31

195.00

Adjusted p-value

Apoptosis

195.00

Adjusted p-value

E2F Targets

MYC Targets V1

0.01

P53 Pathway

Apoptosis E2F Targets MYC Targets V1 G2M Checkpoint

miR-34

EGFR Signaling

setSize

≤ 150.00

249.50

MYC Targets V1

setSize

≤ 150.00

171.46

415.00

Adjusted p-value

Oxidative Phosphorylation

196.00

Adjusted p-value

MYC Targets V1

Hypoxia

0.015

0.01501

0.015

E2F Targets

0.01

0.01001

MTORC1 Signaling

0.01

0.005

G2M Checkpoint

0.005

0.00501

TNF-α signaling via NF-κB

0.005

0.00001

-2 0 2

NES

-4

-2

NES

-3 -2 -1 0 1 2 3

NES

-3 -2 -1 0

NES

1 2

Revumenib

Azacitidine

NES 2.280

FDR 0.00011

NES 2.044

FDR 1.11x10-6

NES 1.859

FDR 7.2x10-5

Combination

monotherapy.

treatment

produced consistent pathway-level changes compared with

Gene

set

enrichment

analyses

(GSEA)

showed

enhanced

myeloid

differentiation signatures with the addition of lintuzumab-Ac225 to revumenib, gilteritinib, and

azacitidine.

Across models, combinations were associated with downregulation of proliferative programs, including MYC target genes, E2F targets, and G2/M checkpoint signatures, together with enrichment of p53-associated stress response and apoptosis pathways.

Transcriptional Profiling Shows Combination Treatment caused p53 Pathway Activation, Apoptosis, and Myeloid Differentiation Signatures

MV-4-11

100

Gilteritinib

Lintuzumab-Ac225 Combination

Lint-Ac225 + Gilt

MV-4-11

100

Revumenib

Lintuzumab-Ac225 Combination

Lint-Ac225 + Revu

OCI-AML3

Revumenib

Lintuzumab-Ac225

HL60

100

Combination

Lint-Ac225 + Revu

**** ****

*** ****

****

100

5-Azacytidine

Lintuzumab-Ac225 Combination

Lint-Ac225 + 5-AZA

****

***

**** *

**** ****

****

**** ****

***

**** ****

***

**** ****

****

**** ****

****

Combining lintuzumab-Ac225 with targeted agents significantly increased cytotoxicity

compared with monotherapy, demonstrating broad, mutation-independent potentiation of anti-leukemic activity.

Lintuzumab-Ac225 Combination with SOC Enhances AML Cytotoxicity

Viability (%)

Mean Tumor Volume +/-SE (mm3)

Mean Tumor Volume +/- SE (mm3)

Probability of Survival

Mean Tumor Volume +/-SE (mm3)

Untreated

2.6 nM

4.4 nM

1.4 nCi/mL

4 nCi/mL

1.4 nCi/mL + 2.6 nM

1.4 nCi/mL + 4.4 nM

4 nCi/mL + 2.6 nM

4 nCi/mL + 4.4 nM

Untreated

7.1 nM

35.7 nM

1.4 nCi/mL

4 nCi/mL

1.4 nCi/mL + 7.1 nM

1.4 nCi/mL + 35.7 nM

4 nCi/mL + 7.1 nM

4 nCi/mL + 35.7 nM

Untreated

8.6 μM

21.1 μM

0.5 nCi/mL

3.5 nCi/mL

0.5 nCi/mL + 8.6 μM

0.5 nCi/mL + 21.1 μM

3.5 nCi/mL + 8.6 μM

3.5 nCi/mL + 21.1 μM

Untreated

1,000 nM

10,000 nM

3.8 nCi/mL

22.4 nCi/mL

3.8 nCi/mL + 1,000 nM

3.8 nCi/mL + 10,000 nM

22.4 nCi/mL + 1,000 nM

22.4 nCi/mL + 10,000 nM

Background

Acute myeloid leukemia (AML) is a genetically heterogeneous and aggressive malignancy with limited durable treatment options.
Actimab-A (Lintuzumab-Ac225, Lint-Ac225), a CD33-targeted antibody radioconjugate, delivers the alpha emitter actinium-225 (Ac-225) to AML cells, inducing potent, localized DNA damage.
Clinical studies have shown encouraging responses when combined with CLAG-M chemotherapy in relapsed/refractory AML, including in patients with TP53 mutations or venetoclax resistance.
Lintuzumab-Ac225 has shown potent anti-leukemic activity in AML cells regardless of mutations (FLT3, TP53, NPM1, and KMT2A) in both in vitro and in vivo AML models.
Here, we demonstrated in primary AML patient samples that lintuzumab-Ac225 has strong translational therapeutic potential both as monotherapy and in combination with standard of care (SOC) therapies.
We also defined the transcriptional profiles of AML cells treated with lintuzumab-Ac225 combination therapies to understand the underlying molecular mechanisms of anti-leukemic activity of these combination treatments.

Poster Number: 5827

Combination therapies with lintuzumab-Ac225 induce double-stranded DNA damage, which causes Myc to be downregulated and p53 to be upregulated in AML models.
Cyclin B-CDK1 complex degradation leads to G2-M arrest and prevents retinoblastoma protein phosphorylation and downregulates E2F target genes.

Mechanism of Action: Lintuzumab-Ac225 Combination with SOC

AML Cell Line	Menin Inhibitors		FLT3 Inhibitors		Targeting CD33		AML Cell Line	Chemo Agent		Targeting CD33
	Revumenib (nM)		Gilteritinib (nM)		Lintuzumab-Ac225 (nCi/mL)			5-Azacitidine (μM)		Lintuzumab-Ac225 (nCi/mL)
	IC25	IC50	IC25	IC50	IC25	IC50		IC25	IC50	IC25	IC50
MV-4-11	7.1	35.7	2.6	4.4	1.4	4	HL60	8.6	21.1	0.5	3.5
OCI-AML3	~1,000	~10,000			3.8	22.4

Conclusions

Actimab-A (lintuzumab-Ac225) shows broad mutation-
independent anti-leukemic activity in AML cell lines and Actinium Pharmaceuticals
primary AML patient samples. posters are available at the following QR code:
When combined with standard therapies, Actimab-A drives complementary transcriptional programs that enhance depth and durability of response.
These findings support the clinical evaluation of Actimab-A combinations as a strategy to overcome resistance and enhance therapeutic efficacy in AML.

Preparation of

Lintuzumab-Ac225

MV-4-11

OCI-AML3

HL60

NCI-H1975

Unstained

Lint Lint-DOTA Lint-Ac225

KMT2A / NPM1

FLT3

TP53

CD33 ARC

120

100

120

100

Concentration (nM)

MV-4-11 Revumenib

MV-4-11 Vehicle (DMSO)

Concentration (nM)

MV-4-11 Gilteritinib

MV-4-11 Vehicle (DMSO)

Concentration (μM)

HL60 5-Azacitidine HL60 Vehicle (DMSO)

OCI-AML3 Revumenib

OCI-AML3 Vehicle (DMSO)

Concentration (nCi/mL)

MV-4-11 Lintuzumab-Ac225 MV-4-11 Lintuzumab

OCI-AML3 Lintuzumab-Ac225 OCI-AML3 Lintuzumab

HL60 Lintuzumab-Ac225

HL60 Lintuzumab

Lintuzumab-Ac225 has Potent Binding and Robust Cytotoxicity in AML Cell Line Panel with Different Mutations

Patient 1

(FLT3 & IDH1)

Patient 2

(NPM1)

Patient 3

(KMT2A & FLT3)

Patient 4

(TP53 & IDH1)

✱✱✱✱

✱

✱✱

✱✱✱✱

✱

100

✱✱

100

Lintuzumab-Ac225 showed a robust cytotoxicity in primary AML patient samples,
irrespective of FLT3, KMT2A, NPM1, IDH1 or TP53 status.
Combining SOC therapies with lintuzumab-Ac225 enhanced efficacy.

Lintuzumab-Ac225 Combination with SOC Enhances Cytotoxicity in Primary AML Patient Samples

Cell Viability (% of control)

Viability (%)

0.001

0.01

0.1

100

1,000

10,000

100,000

Untreated

Lintuzumab

DMSO

Lint-Ac225 1,000 nCi/mL

Gilt 2,000 nM

Combination

Untreated

Lintuzumab

DMSO

Lint-Ac225 500 nCi/mL

Revu 50 nM

Combination

0.01

0.1

100

1,000

10,000

100,000

0.001

0.01

0.1

100

1000

10000

0.001

0.01

0.1

100

1,000

No Treatment

Lint

DMSO

2,000 nCi/mL 225Ac-Lint

100 nM Revu

Combination

Untreated

Lintuzumab

DMSO

Lint-Ac225 2,000 nCi/mL

5-AZA 5 μM

Combination

AML Cell Line Panel
Cell Line	KMT2A	FLT3	NPM1	TP53	CD33
MV-4-11	MLL-AFF1	ITD		WT	Positive
OCI-AML3			NPM1	WT	Positive
HL60				Deletion	Positive
NCI-H1975					Negative

American Association for Cancer Research (AACR). San Diego, CA April 17-22, 2026

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