30 slides from Actinium Pharmaceuticals, Inc. (delaware)'s technical presentation, Feb 28, 2023
Slide 1: KOL Call with Dr. Sergio Giralt
KOL Call with Dr. Sergio Giralt Iomab-B Pivotal Phase 3 SIERRA Results February 28, 2023 ATNM: NYSE AMERICAN
Slide 2: Today’s Agenda
Today’s Agenda 1) Iomab-B Pivotal Phase 3 SIERRA Trial Results – Dr. Sergio Giralt 2) Moderator Led KOL Q&A – Dr. Sergio Giralt 3) Live Q&A – Dr. Sergio Giralt and Actinium 2
Slide 3: Dr. Sergio Giralt
Dr. Sergio Giralt Deputy Division Head, Division of Hematologic Malignancies Melvin Berlin Family Chair in Multiple Myeloma Chief Medical Officer, MSK Direct Attending Physician, Adult Bone Marrow Transplant Service Professor of Medicine, Weill Cornell Medical College § Clinical and research activit
Slide 4: Efficacy and Safety Results of the SIERRA Trial: A Multicenter, Pivotal Phase 3 Study
Efficacy and Safety Results of the SIERRA Trial: A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Older Patients with Active, Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) Boglarka Gyurkocza, MD, Stuart Serop
Slide 5: Acknowledgement of SIERRA Trial Sites
Acknowledgement of SIERRA Trial Sites 5
Slide 6: Iomab-B and SIERRA Trial Overview
Iomab-B and SIERRA Trial Overview § Patients with active, R/R AML have a dismal prognosis, particularly with increasing age, and typically are not offered allogeneic HCT due to failure to achieve remission, poor tolerance of conditioning, and substantial transplant-related mortality § SIERRA was des
Slide 7: Dismal Prognosis for Older R/R AML Patients
Dismal Prognosis for Older R/R AML Patients Transplant remains the only curative option for R/R AML despite multiple drug approvals 21,000 patients diagnosed with AML annually1; biggest indication for Allo-HCT 68 years Median age at diagnosis, >70% age 55 or above1; outcomes for older patients remai
Slide 8: Factors Preventing Patients From the Benefits of a BMT
Factors Preventing Patients From the Benefits of a BMT Hurdles to a successful BMT R/R AML Patient Risks, Limitations Not in CR, Need to get Into CR Unable to tolerate intensive chemotherapy to induce CR Receive Effective Conditioning Unable to tolerate myeloablative conditioning, RIC conditioning t
Slide 9: Current Conditioning Regimens for BMT
Current Conditioning Regimens for BMT Chemotherapy and Radiation are used at varying intensities for conditioning to enable a BMT § Conditioning uses chemotherapies that have been used for decades and non-targeted total body irradiation § Various combinations and intensities based on patient’s “fitn
Slide 10: Iomab-B: Targeted Treatment for Disease Control and Conditioning
Iomab-B: Targeted Treatment for Disease Control and Conditioning Iomab-B § Iomab-B targets CD45, which has high expression Leukemia only in AML immune and stem cells, thereby sparing Cells organs and increases tolerability § Supported by data in 400 patients, in 6 disease Immune Cells indications wi
Slide 11: SIERRA: Study of Iomab-B in Elderly R/R AML
SIERRA: Study of Iomab-B in Elderly R/R AML Accrual Target: N=150 No CR Endpoints: Iomab-B HCT Pre-Specified Primary: dCR = CR/CRp lasting CR dCR ≥180 days post-CR Crossover* Active, Relapsed Secondary: OS and EFS *Control arm subjects with RANDOMIZED 1:1 no CR offered crossover or Refractory AML No
Slide 12: Personalized Single Dose Combined Induction/Conditioning
Personalized Single Dose Combined Induction/Conditioning RIC Dosimetric Dose Therapeutic Dose FLU TBI ≤20 mCi • Upper limit of 24 Gy to liver 30 mg/m2/d 200 cGy • Median 16 Gy to marrow HCT Day: -19 -18 -15 -12 -4 -3 -2 -1 0 Imaging Tac/CSA + MMF RIC: reduced intensity conditioning; FLU: fludarabine
Slide 13: SIERRA Trial CONSORT Chart
SIERRA Trial CONSORT Chart 153 Pts Randomized Iomab-B Conventional Care N=76 N=77 1 pt did not • 4 pts did not receive receive chemo dosimetric dose • 6 pts did not proceed to therapeutic dose with HCT No CR Achieved CR N=62 N=14 66 patients received Crossover to Iomab-B therapeutic dose N=44 4 pts
Slide 14: Patient Characteristics
Patient Characteristics Complete Enrollment, N = 153 Randomized to Conventional Iomab-B Arm (N=76) Conventional Care Arm (N=77) Care and Crossed Over to Iomab-B (N=44) Age, years Median 64 (55-77) 66 (55-76) 64 (55-76) (Range) Pts ≥70 yrs: 14 (18.4%) Pts ≥70 yrs: 16 (20.8%) Pts ≥70 yrs: 12 (27.3%) C
Slide 15: Conditioning and Transplant Characteristics
Conditioning and Transplant Characteristics Iomab-B (N=66)1 Standard HCT (N=14) Crossover (N=40)2 Infused Activity 664.4 mCi (354-1027) N/A 613.3 mCi (313-1008) Median (Range) Dose to the Marrow 16 Gy (4.6-44.6) N/A 16 Gy (6.3-39.8) Median (Range) Time to HCT From Randomization 29 Days (23-60) 66.5
Slide 16: Superior dCR Rate for Iomab-B versus CC
Superior dCR Rate for Iomab-B versus CC dCR assessed by Independent Endpoint Adjudication Committee Iomab-B CC N (%) N (%) Evaluable Per-Protocol* 59 64 Achieved CR/CRp 44 (74.6) 4 (6.3) Maintained dCR 13 (22.0) 0 (0.0) of ≥180 days p<0.0001; 95% CI [12.29, 34.73] ‒ In the crossover arm (N=44), 91%
Slide 17: Iomab-B Doubles Overall Survival Compared to CC
Iomab-B Doubles Overall Survival Compared to CC Iomab-B (N=76) CC Only (without Crossover) (N=33) Overall Survival (mos) Median (95% CI) 6.4 (5.1, 7.9) 3.2 (1.6, 7.0) One-Year Survival % (95% CI) 26.0 (16.7, 36.4) 13.1 (4.2, 27.4) Duration of Follow-up (mos) Median (Range) 6.3 (0.5-49.5) 3 (0.6-28.8
Slide 18: Maintenance Therapy May Further Improve Outcomes
Maintenance Therapy May Further Improve Outcomes § For patients randomized to Iomab-B, there was highly restrictive options for maintenance therapy limited to FLT3 inhibitors and TKIs § In practice, we would start maintenance therapy for these patients who have a high-risk of relapse § Iomab-B outco
Slide 19: Iomab-B Superior to CC Across a Majority of Subgroups
Iomab-B Superior to CC Across a Majority of Subgroups § Forest Plot of Hazard Ratios for Overall Survival – Iomab-B, N=76; CC (without Crossover), N=33 1 2 3 1. PIF: Primary induction failure; FER: First early relapse; RR: Relapse refractory; SSR: Second or subsequent relapse. 2. Median 3 prior regi
Slide 20: Significantly Improved Event-Free Survival with Iomab-B Versus CC
Significantly Improved Event-Free Survival with Iomab-B Versus CC EFS in Intent-to-Treat Groups Iomab-B (N=76) CC (N=77) HR 0.22 (95% CI [0.15, 0.34]) EFS at 180 days 28% 0.2% p<0.0001 Events defined as: § Induction treatment Event-Free Survival Probability (%) failure (ITF), defined as day of rando
Slide 21: Long-Term Survival in Patients with dCR on Study Arm
Long-Term Survival in Patients with dCR on Study Arm Rate of OS at: Iomab-B (N=13) CC (N=0) 6 months 100% 12 months 92.3% NA 18 months 71.9% 24 months 59.9% Overall Survival Probability (%) Time (Months) 21
Slide 22: Favorable Safety Profile for Iomab-B Compared to CC
Favorable Safety Profile for Iomab-B Compared to CC Grade ≥3 Treatment-Emergent Adverse Events in Transplanted Patients Through Day 100 Post-HCT Adverse Event Iomab-B (N=66) CC (N=14) Sepsis1 4 (6.1) 4 (28.6) N (%) Febrile Neutropenia 29 (43.9) 7 (50.0) N (%) Mucositis2 10 (15.2) 3 (21.4) N (%) Acut
Slide 23: Iomab-B Patient Care is Easily Managed
Iomab-B Patient Care is Easily Managed § SIERRA trial conducted at 22 leading U.S. BMT centers treating over 100 patients with Iomab-B − Established procedures and protocols in place for patient care will facilitate commercial efforts § MSKCC utilized Actinium shielding solutions for the majority of
Slide 24: Iomab-B Next Steps
Iomab-B Next Steps § Positive efficacy and safety results demonstrate benefit of Iomab-B in older R/R AML patients with active disease § SIERRA met primary endpoint of dCR >180 days with high statistical significance<0.0001 § dCR is the appropriate endpoint in this setting and trial designed with FD
Slide 25: Distinguishing SIERRA from the ASAP Trial
Distinguishing SIERRA from the ASAP Trial Objective of SIERRA & ASAP: Key Difference: Take patients with R/R AML to transplant R/R AML Palliative care patients otherwise ineligible for HCT successfully transplanted in SIERRA while these unfit patients were excluded from ASAP trial SIERRA ASAP § ASAP
Slide 26: Potential to Increase Transplants in R/R AML
Potential to Increase Transplants in R/R AML Current Status ASAP Trial Iomab-B Impact Not Not Iomab-B Transplantable Transplantable HCT No HCT ASAP HCT HCT § Only fit patients who achieve § Fit patients able to tolerate § Vast majority of R/R AML remission are taken to HCT intensive therapy with act
Slide 27: Conclusion
Conclusion § SIERRA trial results demonstrate the viability of successfully transplanting R/R AML patients, who are currently offered palliative care, and improving their outcomes thereby paving the way for Iomab-B to become a new standard of care § Iomab-B achieved the SIERRA trial primary endpoint
Slide 28: Moderator Q&A with KOL
Moderator Q&A with KOL Actinium Pharmaceuticals, Inc.
Slide 29: Audience Q&A with KOL and Company
Audience Q&A with KOL and Company Actinium Pharmaceuticals, Inc.
Slide 30: Thank you
Thank you February 18, 2022 Actinium Pharmaceuticals, Inc. ATNM: NYSE AMERICAN