43 slides from Actinium Pharmaceuticals, Inc. (delaware)'s technical presentation, Mar 25, 2025
Slide 1: Actimab-A KOL Call and Company Update
Actimab-A KOL Call and Company Update KOL Webinar March 25, 2025 ATNM: NYSE AMERICAN
Slide 2: Disclaimer and Safe Harbor
Disclaimer and Safe Harbor The information presented herein contains express and implied forward-looking statements regarding the current intentions, expectations, estimates, opinions and beliefs of Actinium Pharmaceuticals, Inc. (“Actinium”) that are not historical facts. These forward-looking stat
Slide 3: Actinium Company Update
Actinium Company Update February 18, 2022 Revitalized Clinical Programs and Expanded Market Opportunities for Actimab-A and Iomab-ACT Set Stage for Milestone Rich 2025 ATNM: NYSE AMERICAN
Slide 4: Today’s Speakers and Agenda Highlights
Today’s Speakers and Agenda Highlights Data Driving Broad Program Expansion Company Update & Development of Leveraging Mutation Outlook Actimab-A in Myeloid Agnostic Mechanism Malignancies and Targeting MDSCs Sandesh Seth - in Solid Tumors Actinium Dr. Ehab Atallah – Medical College of Dr. Madhuri W
Slide 5: 2025: Revamped Strategy, Revitalized Programs To Drive Value Creation
2025: Revamped Strategy, Revitalized Programs To Drive Value Creation Actimab-A Iomab-ACT Capabilities ✓ Market expansion with initiation of ✓ Commercial CAR-T initiated at ✓ In-house R&D continues to support frontline AML trial under NCI UTSW, data expected in 2H:2025 expansion of Actimab-A via CRA
Slide 6: Three Blockbuster Opportunities with Our First-in-Class Radiotherapies
Three Blockbuster Opportunities with Our First-in-Class Radiotherapies 400,000 375,730 350,000 Number of Patients 300,000 268,100 250,000 200,000 150,000 124,970 100,000 Actimab-A 100,000 88,000 50,000 Iomab-ACT 23,000 - Active Trial AML MDS CAR-T Sickle Cell HNSCC & NSCLC Other Solid Disease Tumors
Slide 7: Significant Milestones Expected in 2025 Across Pipeline
Significant Milestones Expected in 2025 Across Pipeline Initiative Program 2025 Objective & Expected Accomplishments by Year-End Timing Hematology Actimab-A Established as Backbone Therapy in AML & Myeloid Malignancies • Phase 2/3 trial initiated in R/R AML, Seek Partner/Collaborator 2H • Generate i
Slide 8: Today’s KOL: Dr. Ehab Atallah
Today’s KOL: Dr. Ehab Atallah ▪ Professor of Medicine, Hematology – Oncology at Medical College of Wisconsin ▪ Co-chair of the Eastern Cooperative Oncology Group (ECOG) leukemia committee ▪ Research efforts focused on treatment of patients with AML, ALL, CLL, CML, MDS and MPNs ▪ Fellowship in Leukem
Slide 9: Actimab-A (lintuzumab-Ac225): Addressing Unmet Needs of Patients with Acute Myeloid Leukemia
Actimab-A (lintuzumab-Ac225): Addressing Unmet Needs of Patients with Acute Myeloid Leukemia
Slide 10: Acute Myeloid Leukemia and CD33
Acute Myeloid Leukemia and CD33 • Most common adult leukemia • Lowest 5-year survival of any blood cancer • Median age of diagnosis is 68 • Occurs when blood cells fail to differentiate, known as AML blasts • Blasts overpopulate the blood and prohibit normal blood and immune function • Complex, diff
Slide 11: Actimab-A: CD33 Targeted Radiotherapy
Actimab-A: CD33 Targeted Radiotherapy Actimab-A is the only targeted alpha-emitting radiotherapy in development for AML • Actimab-A is comprised of Lintuzumab, a humanized anti- CD33 antibody linked to Actinium-225, delivering high-energy alpha particles to leukemic blasts resulting in double strand
Slide 12: Actimab-A: Compelling Single Agent Activity
Actimab-A: Compelling Single Agent Activity Actimab-A Monotherapy in Newly Diagnosed AML Actimab-A Phase 2: Potent Anti-Leukemic age 60+ Activity Bone Marrow Blast % Change Fractionated Response Rate (%) # Patients Dose Level 0.5 µCi/kg/1 0% 3 1.0 µCi/kg1 17% (1 CR) 6 1.5 µCi/kg2 22% (3 CRp, 3 CRi)
Slide 13: CLAG-M is MCW’s Preferred Salvage Therapy
CLAG-M is MCW’s Preferred Salvage Therapy Responses to Salvage Chemotherapy1 CLAG-M is our salvage chemotherapy 60% regimen of choice for r/r AML and is 50% used increasingly at leading centers 40% 30% • Cladribine (approved for hairy cell leukemia) 20% • Cytarabine (approved for combination use in
Slide 14: Study Design and Treatment
Clinicaltrials.gov identifier: NCT03441048 Study Design and Treatment Primary Objective • Determination of MTD and RP2D Secondary Objectives • PK Profile of Lintuzumab Ac225 • Response (CR, CRi, MLFS) • MRD(-) Response by MFC • Transplant eligible who proceed to HCT • Two-year OS Key Eligibility Cri
Slide 15: Baseline Characteristics
Baseline Characteristics AML type at screen, n (%) Relapsed 5 (19) 5 (21.7) Total Enrolled Efficacy Cohort Refractory 21 (81) 18 (78.3) N=26 N=23 2017 ELN cytogenetic risk, n (%) Age (years) Favorable 2 (8) 2 (8.7) Median (range) 58 (20,73) 62 (20,73) Intermediate 3 (11.5) 3 (13) Gender, n (%) Femal
Slide 16: Treatment Emergent Adverse Events
Treatment Emergent Adverse Events No Dose Limiting Toxicity observed at the Recommended Phase 2 Dose RP2D All Patients (n=23) 0.75uCi/kg (n=8) No. % No. % Any Adverse Event 23 100 8 100 Grade 3-4 Adverse Event 23 100 8 100 Dose Limiting Toxicity* 4 17 0 0 Adverse Event All Patients (n=23) 0.75uCi/kg
Slide 17: Pharmacokinetics and Safety
Pharmacokinetics and Safety • Actimab-A clears rapidly, detectable total radioactivity no longer quantifiable at a median of 24.5 hours • No significant kidney or liver toxicity reported to date • No incidences of VOD Ac-225 Radioactivity after 0.75uCi/kg AUC0-last (h*ngEq/g) 87.8 (39.4) Cmax (ngEq/
Slide 18: Remissions, Responses and MRD-
Remissions, Responses and MRD- CRc ORR High Rates of MRD Negativity in High-Risk CR (CR/CRi) (CR/CRi/MLFS) R/R Patients All (n=23) n (%) 4 (17.4) 13 (56.5) 15 (65.2) Prior Lines of Therapy 1 or 2 (n=14) n (%) 3 (21.4) 11 (78.5) 11 (78.5) >3 1 (11.1) 2 (22.2) 4 (44.4) High-risk AML (n=20) All High-ri
Slide 19: Overall Survival in High-Risk Patients
Overall Survival in High-Risk Patients Overall Survival Compares Favorably to Reported Outcomes in High-Risk Patients Median Overall Patient segment Survival 1st/2nd Salvage (n=14) 18.4 mo. Underwent allo HCT (n=5) 24 mo. TP53mut (n=13) 9.6 mo. Prior Venetoclax (n=13) 7.3 mo. 1) Maiti et al. Outcome
Slide 20: Conclusions
Conclusions CLAG-M salvage chemotherapy and Actimab-A can safely be administered - The recommended phase II dose for Actimab-A identified in this study is 0.75uCi/kg - Hematologic toxicities observed on study were expected, we did not observe significant kidney, liver toxicities or VOD - Responders
Slide 21: Actimab-A + CLAG-M Phase 2/3 Trial
Actimab-A + CLAG-M Phase 2/3 Trial Phase 2 – Expected to Initiate in 2025 Phase 3 Actimab-A RP2D-1 +CLAG-M Treatment arm Randomization Actimab-A + CLAG-M (1:1:1) Dose Optimization Actimab-A RP2D +CLAG-M Dose Optimization FDA Meeting 1:1 randomization FDA Meeting Control arm CLAG-M CLAG-M • Highly no
Slide 22: NCI Advancing Actimab-A in Frontline AML
NCI Advancing Actimab-A in Frontline AML • The combination of Venetoclax + hypomethylating agents (HMAs) has become standard of care in the treatment of AML, however, the need for improved outcomes remains • This collaboration in front line AML is supported by the demonstrated synergy between radiot
Slide 23: Actimab-A’s Broad Development Potential
Actimab-A’s Broad Development Potential Pivotal, Operationally Seamless, Phase 1b, Multicenter Dose Additional Trial Concepts Phase 2/3 Study: Actimab-A Escalation Study : Actimab-A with being Evaluated Under +CLAG-M in R/R AML VEN + HMA in Frontline AML NCI CRADA MUTATION-AGNOSTIC MECHANISM OF ACTI
Slide 24: Dr. Madhuri Vusirikala, VP, Clinical Development BMT & Cell Therapy
Dr. Madhuri Vusirikala, VP, Clinical Development BMT & Cell Therapy • Joined Actinium in October 2022 as Vice President, Clinical Development, Transplant & Cellular Therapy • Over 20 years of clinical experience specializing in adult allogeneic bone marrow transplant • Most recently, Director of the
Slide 25: Actimab-A Reimaged, Revitalized
Actimab-A Reimaged, Revitalized February 18, 2022 Leveraging its mutation agnostic backbone therapy potential in myeloid malignancies via multiple clinical initiatives with NCI Potential to synergize with PD-1 and other immune checkpoint inhibitors in solid tumors ATNM: NYSE AMERICAN
Slide 26: Mutation Agnostic Backbone Therapy Potential
Mutation Agnostic Backbone Therapy Potential CD33 Backbone target Ac-225 Mutation Agnostic • Double strand DNA breaks are lethal 1 • No known resistance or repair mechanism • Cell killing regardless of genetic mutations Mourtada et al. Actinium-225 Targeted Agents: Where Are We Now? Brachytherapy. 2
Slide 27: AML: Heterogenous and Mutation Rich Disease
AML: Heterogenous and Mutation Rich Disease Actimab-A’s Backbone Therapy Profile Across Major AML <50% of patients Mutations and Synergy in Combinations Have High-Risk disease Target Expression in Actimab-A Data AML ~97% of patients NMP1 & KMT2A 30% Yes have at least 1 driver mutation FLT3 25-30% Ye
Slide 28: Demonstrated Synergy with Successful Commercial AML Therapies
Demonstrated Synergy with Successful Commercial AML Therapies Anti-leukemic effect in FLT3 cell lines and Potent cell killing in IHD 1&2 Mutated Cell Lines synergy with FLT3 inhibitors • FLT3 is expressed in ~30% of AML patients • IDH1&2 is expressed in 10-20% of AML patients • 3 approved FLT3 thera
Slide 29: Demonstrated Synergy with Newly Approved/Emerging Menin Inhibitors
Demonstrated Synergy with Newly Approved/Emerging Menin Inhibitors Significant tumor inhibition via combination of Actimab-A displays synergy with both Revumenib Actimab-A and Revumenib and Ziftomenib, leading menin inhibitors • Menin inhibitors address ~40% of AML patients with AML who have NPM-1 (
Slide 30: Actimab-A for MDSC Depletion in Solid Tumors with PD-1 Inhibitors
Actimab-A for MDSC Depletion in Solid Tumors with PD-1 Inhibitors • Myeloid-derived suppressor cells (MDSC) function • MDSCs suppress the immune system by various mechanisms and inhibit anti-tumor immunity • Impact on PD-1s and immune checkpoint inhibitors (ICI’s) • High levels of MDSCs in a tumor m
Slide 31: Increased MDSCs – Worse Response Outcomes (NSCLC Case Study)
Increased MDSCs – Worse Response Outcomes (NSCLC Case Study) High MDSCs result in poor tumor Low MDSCs associated with statistically response significant improvement in PFS and OS Low High MDSCs MDSCs PFS 8.39 1.94 OS 15.15 3.03 • MDSCs were the only immune cell subtype to show a statistically signi
Slide 32: MDSC Depletion by Targeting CD33 Demonstrated in Solid Tumors
MDSC Depletion by Targeting CD33 Demonstrated in Solid Tumors Anti-CD33 ADC Mylotarg (Gemtuzumab ozogamicin) depletes MDSC Rich Solid Tumors with High CD33 Expression CD33+ MDSCs and restores T-cell proliferation tumor normal Data supports use of CD33 targeted radiotherapy to deplete MDSCs to restor
Slide 33: In Vivo: CD33 ARC Depletes MDSCs in Tumor Bearing Humanized Mice
In Vivo: CD33 ARC Depletes MDSCs in Tumor Bearing Humanized Mice Lintuzumab-Ac225 Lint-Ac225 Targets causes human Human MDSC MDSC Depletion depletion in vivo In Vivo 25 ns ✱✱✱ ✱✱ Lintuzumab % of viable PBMCs 20 Lintuzumab-Ac225 Tested in huNOG-EXL humanized 15 mouse model for MDSCs 10 5 0 Day 10: CD
Slide 34: Actimab-A Solid Tumor Program: Clinical Trials Overview
Actimab-A Solid Tumor Program: Clinical Trials Overview Program comprised of several randomized, head-to-head controlled clinical trials in HNSCC and NSCLC; Trials will compare Actimab-A + KEYTRUDA® vs KEYTRUDA® alone and Actimab-A + OPDIVO® vs OPDIVO® alone Patient Population Endpoints: • Evaluate
Slide 35: Iomab-ACT
Iomab-ACT February 18, 2022 Universal targeted conditioning regimen for cell & gene therapies to improve patient access and outcomes ATNM: NYSE AMERICAN
Slide 36: Iomab-ACT: Targeted Conditioning for Cell & Gene Therapies
Iomab-ACT: Targeted Conditioning for Cell & Gene Therapies Novel Mechanism of Action with Compelling PoC Clinical Data from Novel CAR-T Targeted CD45+ Immune Cell Ablation Conditioning Clinical Trial Phase 1/2 clinical collaboration with MSKCC funded by (Low Dose I-131-Apamistamab) NIH Grant Prior P
Slide 37: Investigator Initiated Trials Expected to Inform Pivotal Studies
Investigator Initiated Trials Expected to Inform Pivotal Studies BMT & Gene Therapy Conditioning – Commercial CAR-T Phase 1B/2 Trial Sickle Cell Disease BMT Phase 1 Trial Farrukh Awan, MD Markus Mapara, MD Professor of Internal Medicine Professor of Medicine Enrollment Enrollment N = 30 patients N =
Slide 38: Revitalized and Expanded Actimab-A Program, Iomab-ACT Advancing
Revitalized and Expanded Actimab-A Program, Iomab-ACT Advancing • Transformational opportunity with revitalized Actimab-A program with multiple clinical data readouts starting in 2025 to support late-stage development for patients with unmet medical need in myeloid malignancies and solid tumor indic
Slide 39: Closing Remarks
Closing Remarks February 18, 2022 Revitalized Clinical Programs and Expanded Market Opportunities for Actimab-A and Iomab-ACT Set Stage for Milestone Rich 2025 ATNM: NYSE AMERICAN
Slide 40: Actinium in 2026 Coming into Focus
Actinium in 2026 Coming into Focus Cutting-Edge R&D Advanced Clinical Development Robust Infrastructure ▪ Continued focus on leading ▪ Clinical data in myeloid ▪ Manufacturing facility operational radiotherapy innovation malignancies, cell & gene therapy and supplying Actinium’s clinical conditionin
Slide 41: 2025: Revamped Strategy, Revitalized Programs To Drive Value Creation
2025: Revamped Strategy, Revitalized Programs To Drive Value Creation Hematology Conditioning Solid Tumors Actimab-A Iomab-ACT Actimab-A MDSCs • 2H: Generate initial clinical data in • 1H: Commence patient enrollment • 1H: Commence patient enrollment frontline AML trial under CRADA in both the comme
Slide 42: Q&A
Q&A Actinium Pharmaceuticals, Inc.
Slide 43: Thank you
Thank you February 18, 2022 Actinium Pharmaceuticals, Inc. ATNM: NYSE AMERICAN