Relapsed or refractory AML patients with TP53 mutation known to have dismal outcomes due to limited effective treatment options

已知TP53突变的复发或难治性AML患者由于有效治疗选择有限而预后不佳

Median Overall Survival of 5.49 months observed in patients with a TP53 mutation receiving an Iomab-B led allogeneic bone marrow transplant compared to 1.66 months in patients that did not receive Iomab-B (hazard ratio=0.23, p=0.0002)

接受Iomab-B引导的异基因骨髓移植的TP53突变患者的中位总生存期为5.49个月，而未接受Iomab-B的患者的中位总生存期为1.66个月（危险比=0.23，p=0.0002）

Eighth oral presentation of Iomab-B data since announcement of positive Phase 3 SIERRA Results

自宣布第三阶段SIERRA阳性结果以来，第八次口头介绍Iomab-B数据

NEW YORK, Dec. 11, 2023 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, today announced that results from the Phase 3 SIERRA trial of Iomab-B were presented in an oral presentation at the 65th Annual American Society of Hematology Meeting & Exposition (ASH).

2023年12月11日，纽约/PRNewswire/--Actinium Pharmaceuticals，Inc.（纽约证券交易所美国证券交易所：ATNM）（Actinium或该公司），靶向放射疗法开发的领导者，今天宣布，Iomab-B的3期SIERRA试验结果在第65届美国血液学会年会和博览会（ASH）上进行了口头介绍。

The oral presentation highlighted significantly improved survival in patients with a TP53 mutation receiving Iomab-B..

口头介绍强调了接受Iomab-B的TP53突变患者的生存率显着提高。。

Iomab-B is a targeted radiotherapeutic comprised of an anti-CD45 monoclonal antibody with the Iodine-131 radioisotope payload. The Phase 3 SIERRA trial enrolled 153 patients with active relapsed or refractory acute myeloid leukemia (AML) and compared outcomes of patients receiving Iomab-B and a bone marrow transplant (BMT) to those of patients receiving physician's choice of care in the control arm, which was intended to reflect current best practices.

Iomab-B是一种靶向放射治疗剂，由抗CD45单克隆抗体和碘-131放射性同位素有效载荷组成。SIERRA 3期临床试验招募了153名活动性复发或难治性急性髓细胞白血病（AML）患者，并将接受Iomab-B和骨髓移植（BMT）的患者与接受医生选择的对照组患者的结果进行了比较，旨在反映当前的最佳做法。

Patients not achieving a Complete Remission (CR) in the control arm who were unable to proceed to a BMT were offered to crossover to receive an Iomab-B led BMT..

无法进行BMT的对照组未达到完全缓解（CR）的患者被提供交叉接受Iomab-B领导的BMT。。

Iomab-B achieved the primary endpoint in the SIERRA trial of durable Complete Remission (dCR) of at least 6 months with high statistical significance (p<0.0001), with 22% of patients randomized to the Iomab-B arm achieving dCR and 0% of patients in the control arm achieving dCR, irrespective of TP53 mutational status.

Iomab-B在SIERRA持续完全缓解（dCR）试验中达到了至少6个月的主要终点，具有很高的统计学意义（p<0.0001），22%的患者随机分配到Iomab-B组达到dCR，0%的患者在对照组中达到dCR，无论TP53突变状态如何。

In addition, Iomab-B significantly improved event-free survival, a secondary endpoint, with a hazard ratio of 0.22 and median overall survival (mOS) was doubled..

此外，Iomab-B显着提高了无事件生存率（次要终点），风险比为0.22，中位总生存期（mOS）增加了一倍。。

Data highlighted in the ASH oral presentation, which can be accessed on the investor relations page of Actinium's website, included:

ASH口头报告中强调的数据可在Actinium网站的投资者关系页面上访问，包括：

Overall Survival in Patients with a TP53 Mutation:

TP53突变患者的总生存率：

Iomab-B & Crossover

Iomab-B和交叉

Control Arm

控制臂

Median OS

中位操作系统

5.49 months

5.49个月

1.66 months

1.66个月

Number of Patients

患者人数

27

27

10

10

Hazard Ratio

危险比

0.23

0.23

p-value

p值

0.0002

0.0002

Median OS was 6.37 months in TP53 negative patients receiving Iomab-B and 5.72 months for TP53 positive patients demonstrating Iomab-B's ability to overcome TP53 gene mutations.

接受Iomab-B的TP53阴性患者的中位OS为6.37个月，TP53阳性患者的中位OS为5.72个月，证明了Iomab-B克服TP53基因突变的能力。

Response rates by TP53 Mutation Status:

TP53突变状态的反应率：

Iomab-B & Crossover

Iomab-B和交叉

Control Arm

控制臂

TP53 Positive

TP53阳性

N=27

N=27

N=10

N=10

CR

CR公司

55.56% (15/27)

55.56% (15/27)

0 %

0 %

dCR

dCR

14.81% (4/27)

14.81% (4/27)

0 %

0 %

TP53 Wildtype

TP53野生型

N=93

N=93

N=23

N=23

CR

CR公司

58.06% (54/93)

58.06% (54/93)

17.39% (4/23)

17.39% (4/23)

dCR

dCR

16.13% (15/93)

16.13% (15/93)

0 %

0 %

Dr. Hannah Choe, Assistant Professor of Medicine at Ohio State University and SIERRA trial investigator, commented, 'Patients with a TP53 mutation have notoriously poor outcomes due to resistance to anti-leukemic therapies and are rarely offered access to potentially curative transplantation. Iomab-B can grant patients increased access to transplant and induces high complete remission rates despite active, relapsed/refractory disease and even in those with a TP53 mutation.

俄亥俄州立大学医学助理教授兼SIERRA试验研究者Hannah Choe博士评论道：“TP53突变患者由于对抗白血病疗法的耐药性而预后不佳，很少获得潜在的治愈性移植。尽管存在活动性，复发性/难治性疾病，甚至在TP53突变的患者中，Iomab-B可以使患者获得更多的移植机会，并诱导较高的完全缓解率。

This speaks to the novelty and safety of a CD45-directed radiotherapy. More importantly, we see that these response rates translated into improved overall survival, overcoming the increased risk associated with TP53 mutation while no other viable treatment options exist. We are excited to present these results that further support the use and safety of Iomab for disease control.'.

这说明了CD45定向放射治疗的新颖性和安全性。更重要的是，我们看到这些反应率转化为总体生存率的提高，克服了与TP53突变相关的风险增加，而没有其他可行的治疗选择。我们很高兴提出这些结果，进一步支持Iomab在疾病控制中的使用和安全性。”。

Overall, twenty-four percent (37/153) of patients enrolled on SIERRA had a TP53 mutation. In total, 27 patients with a TP53 mutation received Iomab-B and accessed BMT on the SIERRA trial either after initial randomization or following crossover after not being able to access a BMT on the control arm.

总体而言，在SIERRA登记的患者中，有24%（37/153）患有TP53突变。总共有27名TP53突变患者接受了Iomab-B治疗，并在SIERRA试验中获得了BMT，无论是在初始随机化后还是在无法在对照组上获得BMT后进行交叉。

Only 1 patient with a TP53 mutation was able to access a BMT on the control arm via conventional care..

只有1名TP53突变患者能够通过常规护理在对照组上获得BMT。。

Dr. Avinash Desai, Actinium's Chief Medical Officer, added, 'The SIERRA trial data support that regardless of advanced age, prior therapy, or high-risk cytogenetics including a TP53 mutation, Iomab-B provides unprecedented access to a potentially curative BMT. The results also show that on a population basis and across subgroups, an Iomab-B led BMT may result in improved survival.

Actinium首席医疗官Avinash Desai博士补充说，“SIRRA试验数据支持，无论年龄大，既往治疗或包括TP53突变在内的高风险细胞遗传学，Iomab-B都可以前所未有地获得潜在的治愈性BMT。结果还表明，在人群基础上和亚组之间，以Iomab-B为主导的BMT可能会提高生存率。

We are incredibly excited for the potential of Iomab-B and what it represents for patients with relapsed or refractory AML. The international enthusiasm for the SIERRA data amongst key medical and scientific communities is evidenced by the eight oral presentations at some of the most prestigious medical conferences held this year including TCT, EBMT, ONS, EHA, SNMMI, EANM, SOHO and now ASH is highly motivating, and we are committed to bringing Iomab-B to transplant physicians and their patients globally.'.

我们对Iomab-B的潜力以及它对复发或难治性AML患者的代表性感到无比兴奋。在今年举行的一些最负盛名的医学会议上，包括TCT，EBMT，ONS，EHA，SNMMI，EANM，SOHO和now ASH的八次口头演讲证明了关键医学和科学界对SIERRA数据的国际热情，我们致力于将Iomab-B带到全球移植医生及其患者中。”。

About Iomab-B and the Pivotal Phase 3 SIERRA Trial

关于Iomab-B和关键的3期SIERRA试验

Iomab-B is a first-in-class targeted radiotherapy intended to improve patient access to potentially curative BMT by simultaneously and rapidly depleting blood cancer, immune and bone marrow stem cells that uniquely express CD45. Multiple studies have demonstrated increased survival in patients receiving BMT, however, an overwhelming majority of patients with blood cancers do not receive BMT as current approaches do not produce a remission, which is needed to advance to BMT, or are too toxic.

Iomab-B是一流的靶向放疗，旨在通过同时快速消耗独特表达CD45的血癌，免疫和骨髓干细胞来改善患者获得潜在治愈性BMT的机会。多项研究表明，接受BMT的患者生存率提高，然而，绝大多数血癌患者没有接受BMT，因为目前的方法不能产生缓解，这是进入BMT所必需的，或者毒性太大。

Studied in over 400 patients, prior studies with Iomab-B have demonstrated nearly universal access to BMT, increased survival and tolerability in multiple clinical trials including the recently completed pivotal Phase 3 SIERRA trial in patients with active (leukemic blasts >5%), relapsed or refractory acute myeloid leukemia (r/r AML) age 55 and above..

在400多名患者中进行的研究表明，先前使用Iomab-B进行的研究表明，BMT几乎可以普遍获得，在多项临床试验中提高了生存率和耐受性，包括最近完成的针对活动期（白血病母细胞>5%），复发或难治性55岁及以上急性髓细胞白血病（r/r AML）患者的关键性3期SIERRA试验。。

Iomab-B met the primary endpoint of durable Complete Remission (dCR) of 6 months after initial remission post-BMT in the pivotal Phase 3 SIERRA trial with high statistical significance (p<0.0001). Iomab-B produced a 75% post-BMT CR rate (44/59 patients), which is 12-times greater than the post-BMT rate of 6.3% (4/64 patients) in the control arm.

Iomab-B在关键的3期SIERRA试验中达到了BMT初始缓解后6个月持续完全缓解（dCR）的主要终点，具有很高的统计学意义（p<0.0001）。Iomab-B产生了75%的BMT后CR率（44/59例患者），是对照组BMT后6.3%（4/64例患者）的12倍。

Patients receiving Iomab-B had a 78% lower probability of an event, defined as not achieving a CR/CRp, crossover, not receiving a BMT, relapse or death, with a Hazard Ratio of 0.22 (p<0.0001). Iomab-B doubled 1-year overall survival with 26.1% compared to 13.1% in the control arm for patients who did not crossover as well as median overall survival with 6.4 months vs 3.2 months.

接受Iomab-B治疗的患者发生事件的概率降低了78%，定义为未达到CR/CRp，交叉，未接受BMT，复发或死亡，风险比为0.22（p<0.0001）。Iomab-B使未交叉患者的1年总生存率翻了一番，为26.1%，而对照组为13.1%，中位总生存期为6.4个月vs 3.2个月。

Overall survival statistics are confounded by the crossover arm. Crossover patients had a 35.8% 1-year overall survival rate. Due to its targeted nature, Iomab-B was well tolerated with four times lower rates of sepsis compared to the control arm (6.1% vs. 28.6%) and lower rates of BMT associated adverse events including febrile neutropenia, mucositis and graft versus host disease (GVHD).

总体生存统计数据被交叉臂混淆了。交叉患者的1年总生存率为35.8%。由于其靶向性，与对照组相比，Iomab-B耐受性良好，败血症发生率低四倍（6.1%比28.6%），BMT相关不良事件发生率较低，包括发热性中性粒细胞减少症，粘膜炎和移植物抗宿主病（GVHD）。

Actinium intends to submit a Biologics License Application (BLA) seeking approval for Iomab-B in 2024 to address patients age 55+ with r/r AML who cannot access BMT with currently available therapies. Iomab-B has been granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and has patent protection into 2037..

Actinium打算在2024年提交生物制剂许可证申请（BLA），寻求Iomab-B的批准，以解决55岁以上患有r/r AML的患者，这些患者无法使用目前可用的疗法获得BMT。Iomab-B已被美国食品和药物管理局（FDA）授予孤儿药称号，并在2037年获得专利保护。。

The pivotal Phase 3 SIERRA (Study of Iomab-B in Elderly relapsed or refractory AML) is a 153-patient, randomized, multi-center clinical trial, studying Iomab-B compared to the control arm of physician's choice of salvage therapy. Control arm options included chemotherapies like cytarabine and daunorubicin and targeted agents such as a Bcl-2 inhibitor (Venetoclax), FLT3 inhibitors and IDH 1/2 inhibitors.

关键的3期SIERA（Iomab-B在老年复发或难治性AML中的研究）是一项153名患者的随机多中心临床试验，研究Iomab-B与医生选择的挽救疗法的对照组相比。对照组的选择包括阿糖胞苷和柔红霉素等化学疗法以及Bcl-2抑制剂（Venetoclax），FLT3抑制剂和IDH 1/2抑制剂等靶向药物。

The SIERRA control arm reflects real-world treatment of r/r AML patients with over 20 agents used alone or in combination as no standard of care exists for this patient population. The SIERRA trial enrolled patients at 24 leading transplant centers in the United States and Canada that perform over 30% of AML BMTs..

SIERRA control arm反映了r/r AML患者的现实治疗，其中有20多种药物单独或联合使用，因为该患者人群没有标准的护理。SIERRA试验在美国和加拿大的24个主要移植中心招募了患者，这些移植中心执行了超过30%的AML BMT。。

Developed at the Fred Hutchinson Cancer Research Center, a pioneer in the field of BMT, Iomab-B is supported by data in six disease indications including leukemias, lymphomas and multiple myeloma, which afflict over 100,000 patients annually. Actinium intends to pursue additional indications for Iomab-B beyond AML.

Iomab-B由BMT领域的先驱弗雷德·哈钦森癌症研究中心开发，由六种疾病适应症的数据支持，包括白血病，淋巴瘤和多发性骨髓瘤，每年折磨超过100000名患者。Actinium打算在AML之外寻求Iomab-B的其他适应症。

Actinium also intends to pursue international regulatory approvals independently and through partnerships. In April 2022, Actinium licensed the European, Middle East and North African commercial rights for Iomab-B to Immedica Pharma AB, a fully-fledged independent pharmaceutical company headquartered in Sweden.

Actinium还打算独立并通过合作关系寻求国际监管部门的批准。2022年4月，Actinium将Iomab-B在欧洲、中东和北非的商业权利授予总部位于瑞典的成熟独立制药公司Immedica Pharma AB。

In exchange, Actinium received an upfront payment of $35 million USD with the potential for an additional $417 million USD in regulatory and sales milestones and mid-twenty percent royalties. Europe represents a commercial opportunity approximately double the size of the United States by number of patients with AML receiving BMT.

作为交换，Actinium收到了3500万美元的预付款，另外还有4.17亿美元的监管和销售里程碑以及20%的中期版税。欧洲代表着一个商业机会，接受BMT的AML患者数量大约是美国的两倍。

Iomab-B has been granted Orphan Drug Designation by the European Medicines Agency (EMA) and has received positive Scientific Advice from the Committee for Medicinal Products for Human Use (CHMP) of the EMA indicating that the Phase 3 SIERRA trial design, primary endpoint and planned statistical analysis are acceptable as the basis for a Marketing Authorization Application. .

Iomab-B已被欧洲药品管理局（EMA）授予孤儿药称号，并收到了欧洲药品管理局人类使用药品委员会（CHMP）的积极科学建议，表明第三阶段SIRRA试验设计，主要终点和计划统计分析可作为上市授权申请的基础。。

About Actinium Pharmaceuticals, Inc.

关于Actinium Pharmaceuticals，Inc。

Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia.

锕开发有针对性的放射疗法，以有意义地提高现有肿瘤治疗失败的人的生存率。骨髓移植前的诱导和调理剂Iomab-B（pre-BLA）和治疗药物Actimab-A（National Cancer Institute CRADA pivotal development path）已证明有潜力延长复发和难治性急性髓细胞白血病患者的生存结果。

Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium's technology platform is the basis for collaborations with Astellas Pharma for solid tumors, AVEO Oncology/LG Chem Life Sciences for HER3 solid tumors, and several internal programs in solid tumors.

Actinium计划推进Iomab-B治疗其他血癌，下一代调理候选Iomab ACT改善细胞和基因治疗结果。Actinium的技术平台是与Astellas Pharma合作实体瘤，AVEO Oncology/LG Chem Life Sciences合作HER3实体瘤以及实体瘤内部几个项目的基础。

Actinium holds more than 220 patents and patent applications..

锕拥有220多项专利和专利申请。。

For more information, please visit: https://www.actiniumpharma.com/

有关更多信息，请访问：https://www.actiniumpharma.com/

Forward-Looking Statements

前瞻性声明

This press release may contain projections or other 'forward-looking statements' within the meaning of the 'safe-harbor' provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update.

本新闻稿可能包含1995年《私人证券诉讼改革法案》中“安全港”条款所指的关于公司未来事件或未来财务表现的预测或其他“前瞻性声明”，公司没有义务更新这些预测或声明。

These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the 'SEC'), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time..

这些声明基于管理层当前的预期，并受到可能导致实际结果与预期或估计的未来结果产生重大差异的风险和不确定性的影响，包括与初步研究结果相关的风险和不确定性，这些风险和不确定性与最终结果不同，对正在开发的药物的潜在市场的估计，临床试验，FDA和其他政府机构的行动、监管许可、对监管事项的回应、市场对锕产品和服务的需求和接受程度、临床研究组织的表现以及锕提交给证券交易委员会（“SEC”）的文件中不时详述的其他风险，包括但不限于表10-K中的最新年度报告、表10-Q和表8-K中的后续季度报告，每一份报告都会不时修订和补充。。

Investors:[email protected]

投资者：[受电子邮件保护]

Sources: Granowicz EM, Jonas BA. Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments. Onco Targets Ther. 2022 Apr 21;15:423-436. doi: 10.2147/OTT.S265637. PMID: 35479302; PMCID: PMC9037178.

来源：Granowicz EM，Jonas BA。靶向TP53突变的急性髓细胞白血病：研究和临床发展。Onco以Ther为目标。2022年4月21日；15： doi:10.2147/OTT.S265637。PMID:35479302；PMCID:PMC9037178。

SOURCE Actinium Pharmaceuticals, Inc.

来源Actinium Pharmaceuticals，Inc。