Actinium Pharmaceuticals : Mid-Point Analysis of Pivotal Phase 3 SIERRA Trial Including Material Presented at 2020 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR (TCT)

Actinium

Pharmaceuticals,Inc.

Mid-Point Analysis of Pivotal Phase 3 SIERRA Trial Including Materials Presented at 2020 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR (TCT)

Targeted Conditioning with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] leads to High Rates of Allogeneic Transplantation and Successful Engraftment in Older Patients with Active, Relapsed or Refractory AML after Failure of Chemotherapy and Targeted Agents: Preliminary Midpoint Results from the Prospective, Randomized Phase 3 SIERRA Trial

SIERRA: Study of Iomab-B in Elderly Relapsed/Refractory AML

Boglarka Gyurkocza, MD, Rajneesh Nath, MD, Patrick J. Stiff, MD, Edward Agura, MD, Mark Litzow, MD, Ben Tomlinson, MD, Hannah K. Choe, MD, Sunil Abhyankar, MD, Stuart Seropian, MD, George L.

Chen, MD, Parameswaran Hari, MBBS, MD, Zaid S. Al-Kadhimi, MD, James M. Foran, MD, Johnnie Orozco, MD, Koen Van Besien, MD, PhD, Mitchell Sabloff, MD, Partow Kebriaei, MD, Camille Abboud, MD, Moshe Yair Levy, MD, Hillard M Lazarus, MD, Sergio A Giralt, MD, Mark S. Berger, MD, Vijay Reddy, MD, PhD and John M. Pagel, MD, PhD

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Slides adapted from TCT 2020 oral presentation and include additional data from mid-point analysis of 50% of patients from SIERRA trial

Iodine (131I) apamistamab [Iomab-B] CD45 Targeted Conditioning

• Iodine (131I) apamistamab [Iomab-B] is a murine anti-CD45 targeted therapy that was developed at the Fred Hutchinson Cancer Research Center
• CD45 is expressed on hematopoietic cells, including leukemia, lymphoma and immune cells
• High doses, such as in the SIERRA trial, deplete hematopoietic stem cells
• Targets radiation directly to leukemia cells and elicits a direct anti-tumor effect

Leukemic Bone Marrow

Post-Iomab-B Myeloablated Bone Marrow

Iomab-B

• Compelling prior Phase II clinical data in active, refractory and relapsed AML
• Robust safety and long term efficacy outcomes in multiple populations: 271 patients in 9 Phase I and II clinical trials (AML, ALL, MDS, NHL, MM)

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SIERRA Phase 3 Trial Design

Study Design (N=150)

Primary End-point:	Durable Complete Response Rate (dCR): CR/CRp lasting ≥180 days
Secondary End-point:	1-year Overall Survival

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SIERRA Key Eligibility Criteria

• Bone marrow blast count ≥ 5% or the presence of peripheral blasts
• ≥ 55 years of age
• Karnofsky score ≥ 70
• Medically cleared donor related/unrelated, 8/8 allele-level, matching at HLA-A,HLA-B,HLA-C, and DRB-1
• Secondary AML or treatment-related AML are eligible
• Active, relapsed or refractory AML is defined as either:

1. Primary Induction Failure (PIF) after 2 or more cycles of therapy that includes either chemotherapy OR

Two or more cycles of Venetoclax in combination with Azacitidine or Decitabine (newly added)

1. First early relapse after a remission duration of fewer than 6 months, OR
2. Relapse refractory to salvage combination chemotherapy containing high-dose Cytarabine, OR
3. Second or subsequent relapse

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Analyzing the Inclusion of Targeted Agents in SIERRA

Therapies Prior to Enrollment into the Trial:

85% patients enrolled had failed ≥ 2 regimens (induction/re-induction)

33% had failed targeted therapies Therapies After Enrollment: Control Arm

• 12/38 patients (32%) in the control arm received targeted therapies
• 11/12 patients (92%) received venetoclax + HMA or LDAC
• 3/11 patients (27%) of venetoclax patients went to std of care
  HCT
• 1. Patients receiving a therapeutic dose of Iomab-B

HCT Rate After Iomab-B vs Std of Care Control

100%

(31/31)

Patients of Percentage

18% (7/38) (7/38)

Iomab-B1

Control Arm

Standard of Care BMT

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SIERRA Iomab-B Treatment Schedule

Internal Use Only

Iomab-B Specific

Standard Transplant Procedure

~7 days

~12 days

Therapy Dose

RIC

HCT

Dosimetry

Iomab-B

Iomab-B

FLU

TBI

(~10-20 mCi)

(24 Gy to liver, mean~600mCi)

30 mg/m2/d

200 cGy

	-12 to HCT	-4	-3		-2	-1		0
						Immunosuppression
Imaging

RIC: Reduced Intensity Conditioning FLU: Fludarabine

TBI: Total Body Irradiation

HCT: Hematopoietic Cell Transplant

Therapy dose individualized and calculated based on upper limit of 24 Gy liver exposure

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SIERRA trial: Demographics highlights of first 75 patients (50% Enrollment)

Phase 3 SIERRA Trial Patient Characteristics (N=75)

	Randomized to Iomab-B	Randomized to Conventional Care
	(N=37)	(N=38)
Age	65 (55-77)	64 (55-76)
median, (range)
	Favorable: 0%	Favorable: 5%
Molecular & Cytogenetic Risk1,3	Intermediate: 34%	Intermediate: 29%
	Adverse: 66%	Adverse: 66%
% Bone Marrow Blasts at
Randomization	29% (5-88)2	26% (5-97)
median, (range)
Disease Status at Randomization	Primary Induction Failure: 21 (57)	Primary Induction Failure: 18 (47)
First Early Relapse: 6 (16)	First Early Relapse: 6 (16)
N, (%)	Relapse/Refractory: 6 (16)	Relapse/Refractory: 9 (24)
	2nd + Relapse: 3 (8)	2nd + Relapse: 5 (13)
# Prior Regimens at
Randomization	3 (1-5)	3 (1-5)
median, (range)

1. Data unavailable for two patients in the Iomab-B group
2. 1 patient with 4% blasts in the marrow had circulating AML blasts
3. Per NCCN guidelines version 3. 2020

Randomized to Conventional Care and

Crossed Over to Iomab with HCT

(N=20)

63 (56-72)

Favorable: 5%

Intermediate: 30%

Adverse: 65%

At randomization: 31% (6-87)

At crossover: 35% (5-75)

Primary Induction Failure: 8 (40)

First Early Relapse: 4 (20)

Relapse/Refractory: 7 (35)

2nd + Relapse: 1 (5)

3 (1-5)

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Novel Re-induction and Targeted Conditioning Therapy Yields Encouraging Results in Active, Relapsed or Refractory AML

	Randomized to Study Arm (N=37)	Randomized to Conventional Care (N=38)
	Received Therapeutic Dose of	Achieved CR	Did not Achieve CR (N=31/38)2
	and received standard of	Crossed over, Iomab-B therapy
	Iomab-B, transplanted
	care transplant	and transplanted
	100% (N=31/31)1
		18% (N=7/38)	100% (N=20/20) 2
Days to Absolute
Neutrophil Count	15 (9-22)3	18 (13-82)4	14 (10-37)5
(ANC) Engraftment
Days to Platelet	20 (4-39)3	22 (9-35)4	19 (13-38)5
Engraftment
Days to HCT	30 (23-50)	67 (51-86)	64 (44-161)6
(Post Randomization)

Key Data Highlights:

• Despite high blast counts,100% evaluable patients receiving therapeutic Iomab-B successfully engrafted 3,5
• 7/38 (18%) of patients achieved a CR on the control arm and received a standard of care (SOC) HCT
• 31/38 (82%) of patients did not achieve a CR and 20/31 (65%) of patients crossed over to receive Iomab-B + HCT
• If randomized to conventional care arm, time to HCT after cross over to Iomab-B is consistent with SOC transplant

1. No therapy dose (6) due to: declining KPS (3), Infusion reaction (1), unfavorable biodistribution (1), post-randomization eligibility (1). 2/6 did not receive DI, 4/6 received DI without proceeding to TI.
2. 9 Ineligible for crossover due to: hospice care/progression (4), declined/ineligible for HCT (2), died pre-crossover (3),

2 eligible for crossover and did not receive Iomab-B due to declining status, received DI without proceeding to TI

1. ANC engraftment data not available (1), platelet engraftment data not available (4)
2. ANC and platelet engraftment data not available (1), engraftment failure (1)
3. ANC engraftment data not available (1) out of 20, platelet engraftment data not available (3)
4. 1 patient at 161 days had delayed transplant due to infection and respiratory failure, received Iomab-B and BMT when stable

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100 Days Post-TransplantNon-Relapse Mortality

Favorable safety profile for Iomab-B observed with low 100-daynon-relapse transplant related mortality

	Randomized to Iomab-B (N=37)	Randomized to Conventional Care (N=38)
	Received Iomab-B therapeutic	Achieved CR and received	Did not Achieve CR
	Crossed over to Iomab-B
	dose, transplanted	standard of care transplant
	arm and transplanted
	(N=31)	(N=7)
	(N=20)
100-DayNon-Relapse	2/31	2/7	2/20
Transplant Related
Mortality	(6%)	(29%)	(10%)
Dose Delivered to	15.5 (4.6-32) Gy	n/a	14.4 (6.3-30) Gy
Bone Marrow	616 (366-1027) mCi		560 (313-1008) mCi

Key Data Highlights:

• Lower 100-daynon-relapse transplant related mortality rates observed in Iomab-B arm and cross over than control patients
• Iomab-Bdelivers high amounts of radiation to the site of disease but is well tolerated with minimal extramedullary toxicities due to its targeted mechanism of action

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Non-Heme Grade 3 or 4 AEs (>10% of all patients)

Up to a 100-days post transplant or till crossover assessment*

	Randomized to Iomab-B	Randomized to Conventional
Adverse Event	Study Arm (N=35)	Care Arm (N=37)
	(%)	(%)
Febrile Neutropenia	8 (22.9)	17 (45.9)
Sepsis/Septic Shock	1 (2.9)	8 (21.6)
Pneumonia/Lung Infection	6 (17.1)	7 (18.9)
Device related infection	3 (8.6)	5 (13.5)
Stomatitis (mucositis)	4 (11.4)	4 (10.8)
Hypertension	6 (17.1)	3 (8.1)

Key Data Highlights from Iomab-B study group

• Reduced incidence of febrile neutropenia, low rate of sepsis
• Within expected range of transplant related AEs

Acute GVHD: Grades 2-4 9/31 (29%), Grade 2 (n=6) Grade 3 (n=2) Grade 4 (n=1)

Chronic GVHD: Mild (n=1) Moderate (n=1)

VOD: Grade 1 (N=1). Day 13 to 103 post transplant, Grade 2 (N=1). Day 9 to 17 post transplant. Both Resolved

• Nine subjects on conventional care arm did not achieve CR and did not proceed to crossover. AE profile not collected post cross-over assessment as per protocol ^ Data reported on 72 of 75 Patients in the Intent-to-Treat Analysis Group - 3 subjects with data unavailable at the time of data cut

All AEs reported irrespective of attribution to protocol-directed procedures

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Iomab-B vs Standard of Care HCT group

Non-Heme Grade 3 or 4 AEs in Transplanted Patients (Up to 100-days post transplant)

	Randomized to Iomab-BArm	Randomized to Conventional Care
Adverse Event	and transplanted	with CR and transplanted
	N=31 (%)	N=7 (%)
Febrile neutropenia	8 (25.8)	3 (42.8)
Sepsis/Septic Shock	1 (3.2)	3 (42.8)
Stomatitis (mucositis)	3 (9.7)	2 (28.6)
Pneumonia/Lung Infection	4 (12.9)	1 (14.3)
Hypertension	6 (19.4)1	1 (14.3)
Decreased appetite	5 (16.1)	0 (0.0)
Device related infection	2 (6.5)	1 (14.3)
Hypophosphatemia	2 (6.5)	1 (14.3)

Key Data Highlights:

• Lower incidence of febrile neutropenia, and sepsis in the Iomab-B group
• Reduced incidence of mucositis/stomatitis with Iomab-B compared to standard of care transplant

1. Hypertension considered Unrelated to Iomab-B (5), Possibly related to Iomab-B (1) All AEs reported irrespective of attribution to protocol-directed procedures

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Conclusions from first 50% of Patients Enrolled in SIERRA

SIERRA is the only randomized Phase 3 trial to offer allogeneic HCT to patients with active rel/ref AML

77% of all enrolled patients were able to receive transplant

Only 18% in the control arm achieved remission and were transplanted conventionally

100% engraftment and low Transplant Related Mortality after Iomab-B/HCT Despite high pre-transplant median blast count of ~30%

Low rate of mucositis, febrile neutropenia, and sepsis with Iomab-B

In addition to patients not responding to chemotherapy, patients not responding to venetoclax/HMA are now eligible for SIERRA

1. Agura et al. Novel Re-Induction and Anti-CD45 Targeted Conditioning with Iodine (131I) Apamistamab [Iomab-B] Yields Encouraging Results in Older Patients with Active,

Relapsed or Refractory AML (R/R AML): Safety & Feasibility Data from the Prospective Randomized Phase III Sierra Trial. TCT 2019 Abstract # LBA3

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Acknowledgements and Currently Active Sites

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