Cytarabine/Daunorubicin

01月23日的《热心肠日报》，我们解读了 15 篇文献，关注：沙门氏菌，白血病，益生菌，IBD，乳源外泌体，lncRNA，肠屏障，氧化应激，肠道免疫，粪菌移植，诺华Lutathera，惠升生物加格列净片，声索生物，糖吉医疗，蔚蓝生物。 该篇日报由R·AI辅助创作生成，人工审核校对。 Cell子刊：细菌基因突变导致沙门氏菌长期感染 Cell Host and Microbe——[30.3] ① 对来自256名长期沙门菌病患者的纵向收集的沙门氏菌分离株基因组进行比较分析，探索沙门氏菌持续感染的机制；② 在多个患者和沙门氏菌血清型中，编码全局性转录调控因子的基因经常突变，其中sirA/barA调控系统的遗传变化特别频繁；③ 在多个患者的感染后期分离株中独立出现不同的sirA/barA突变，导致编码毒力相关的基因SPI1/4表达显著降低，而这些基因对于入侵宿主细胞和肠炎的产生至关重要；④ 使用沙门氏菌病小鼠模型，发现sirA/barA基因突变会导致病菌在体内毒力减弱，引发较弱的免疫反应，且可长期定植和脱落；⑤ 因此，沙门氏菌全局毒力调控因子的突变选择，可通过减弱毒力和宿主炎症反应，促使持久感染。 【原文信息】 Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway 2024-01-10 , doi: 10.1016/j.chom.2023.12.001 CPX-351通过肠道菌群，改善白血病治疗 Blood——[20.3] ① 该研究发现CPX-351相对于“7+3”组合在治疗急性髓系白血病（AML）时能够通过保护肠道菌群和黏膜屏障功能，增加抗真菌耐受力，从而提高治疗的安全性和效果；② CPX-351能够保护机体肠道免受肠道微生物紊乱、黏膜损伤和肠道疾病的影响，从而降低感染率和死亡率，是其良好安全性的主要因素；③ CPX-351的保护作用是通过同时影响宿主和肠道微生物群的途径实现的，一方面激活宿主芳香烃受体-IL-22-IL-10通路，另一方面促进厌氧菌免疫调节代谢产物的合成；④ 这项研究为AML的精准医疗提供了新的理解和可能的治疗策略。 【原文信息】 CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance and immune homeostasis 2024-01-16 , doi: 10.1182/blood.2023021380 国内团队：“武装”益生菌，增强肠道定植，精准抗炎靶向递送 Advanced Materials——[29.4] ① 国科温州研究院昝兴杰、李娜团队成功开发了一种响应性可降解纳米装甲，辅助益生菌的超抗性和稳定定植，并增强炎症靶向递送；② 该纳米装甲适用于多种益生菌，且对细菌活力无影响；③ 装甲益生菌对肠道极端环境具有超强的抵抗能力和稳定的粘膜粘附能力；④ 透明质酸功能化的纳米装甲通过多重相互作用赋予益生菌对炎症部位的靶向性，从而增强其IBD治疗功效；⑤ 炎症部位通过响应性转铁蛋白引导的纳米装甲降解，及时“唤醒”摄入的益生菌，有助于细菌治疗充分发挥功能；⑥ 该纳米装甲易于制备且具有良好的生物相容性，为益生菌递送提供了有效的策略。 【原文信息】 Responsively Degradable Nanoarmor-Assisted Super Resistance And Stable Colonization of Probiotics for Enhanced Inflammation-Targeted Delivery 2024-01-19 , doi: 10.1002/adma.202308728 乳源外泌体口服递送TNF-α siRNA或可治疗IBD Bioactive Materials——[18.9] ① 开发一种新型口服递送系统，利用牛奶中的外泌体装载TNF-α siRNA以治疗炎症性肠病；② 相比HEK293T细胞来源的外泌体，乳源外泌体（M-Exos）结构稳定性更显著，更有效装载siRNA；③ M-Exo/siR可抑制TNF-α相关炎症细胞因子的表达；④ M-Exos由高生物利用度的独特脂质组成，在胃肠道中具有卓越稳定性；⑤ 口服M-Exo/siR可有效到达结肠组织，降低TNF-α表达并缓解DSS诱导的小鼠结肠炎；⑥ M-Exo/siR可有效治疗炎症性肠病，为口服基因递送提供新思路。 【原文信息】 Oral TNF-α siRNA delivery via milk-derived exosomes for effective treatment of inflammatory bowel disease 2023-12-22 , doi: 10.1016/j.bioactmat.2023.12.010 长非编码RNA：肠道稳态与炎症的新角色（综述） Trends in Immunology——[16.8] ① 长链非编码RNA（lncRNA）在许多生物学过程中发挥关键作用，其中包括免疫系统从而影响多种炎症性疾病，该综述总结了IncRNA在肠道中的关键作用，阐述了其如何在调节肠道稳态和炎症反应中发挥功能；② lncRNA影响免疫细胞发育、炎症信号通路、上皮屏障功能和细胞代谢从而调控炎症性肠病的发生发展；③ 肠道微生物-寄主互作对于肠道稳态至关重要，一些IncRNA如Snhg9响应免疫和代谢过程从而影响微生物组成；④ lncRNA可能成为潜在的炎症疾病的生物标志物，并为治疗炎症性肠病开辟新的治疗途径，该研究对深入理解肠道疾病的发病机制和寻找新的治疗靶点具有重要意义。 【原文信息】 Lnc-ing RNA to intestinal homeostasis and inflammation 2024-01-13 , doi: 10.1016/j.it.2023.12.005 东北师范：TSP50调节肠屏障完整性，预防结肠炎 Advanced Science——[15.1] ① TSP50蛋白调控细胞增殖、分化和凋亡，与胃癌、结肠癌的不良预后相关，但与结肠炎的关系尚未揭示，东北师范大学的鲍永利和宋振波团队对TSP50与结直肠炎的关系进行了探究；② 基于GTEx数据库发现溃疡结肠炎患者相较健康人肠道TSP50蛋白表达降低，TSP50缺失小鼠更易诱发结肠炎；③ 肠道干细胞中TSP50缺乏引发了TGF-β信号通路的异常激活，阻碍了杯状细胞分化，导致肠黏膜屏障受损，细菌与肠上皮直接接触加重炎症；④ TSP50与TGFβRII相互作用以调节TGF-β下游信号转导；⑤ TGF-β抑制剂成功恢复肠黏膜屏障功能，并减轻TSP50缺失小鼠的结肠炎症状。 【原文信息】 TSP50 Attenuates DSS-Induced Colitis by Regulating TGF-β Signaling Mediated Maintenance of Intestinal Mucosal Barrier Integrity 2024-01-08 , doi: 10.1002/advs.202305893 吕聪+于政权+刘小伟：氧化应激中TDP-43的错位，诱导上皮细胞坏死和肠道炎症 PNAS——[11.1] ① 氧化应激是炎症性肠病（IBD）的重要特征之一，但其分子调节机制却尚不清楚，中国农业大学吕聪、郑州大学和中国农业大学于政权、中南大学湘雅医院刘小伟与团队在PNAS发表研究对此进行了探索；② 研究发现氧化应激引发TDP-43蛋白表达降低、错位，导致R-loop积累、DNA损伤和线粒体依赖的坏死途径激活；③ 而NAD+或其前体NMN的添加可以恢复细胞NAD+水平，抑制线粒体中的α-酮戊二酸双氧酶ALKBH7，进而缓解上皮细胞坏死和肠道炎症；④ 临床样本分析验证了TDP-43缺陷引起的线粒体依赖性坏死与IBD的相关性；⑤ 该研究为IBD的发病机制和治疗提供了重要的理论和实践指导。 【原文信息】 Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation 2023-12-29 , doi: 10.1073/pnas.2307395120 D-丙氨酸或参与免疫调节抑制肠炎 Journal of Crohn's and Colitis——[8] ① D-氨基酸与肠道炎症的关系暂未可知，通过对溃疡性结肠炎（UC）患者和健康人血清调查发现，UC患者血清中D-丙氨酸（D-Ala）低于健康对照；② DSS处理的小鼠血清中D-Ala水平也低于对照，同时补充D-Ala可降低DSS诱导结肠炎小鼠的疾病活动评分，而L-Ala无此效果；③ D-Ala处理小鼠的结肠粘膜中细胞因子IFN-γ、IL-12p35、IL-17A和IL-23p19表达下调；④ 体外实验发现，D-Ala抑制巨噬细胞分化为M1巨噬细胞，促进其向M2巨噬细胞分化，并抑制Naive T细胞分化为Th1 T细胞。 【原文信息】 D-alanine inhibits murine intestinal inflammation by suppressing IL-12 and IL-23 production in macrophages 2024-01-02 , doi: 10.1093/ecco-jcc/jjad217 Nature子刊：PGE2如何调控CD8+T细胞在肠道环境中的代谢适应？ Nature Communications——[16.6] ① 免疫细胞必须适应不同的环境，该研究探究了CD8+ T细胞进入肠道微环境后的适应过程以及在该过程中如何重建CD8+ T细胞群；② 当CD8+ T细胞进入肠壁后，肠道微环境中的前列腺素E2（PGE2）驱动CD8+ T细胞线粒体去极化，下调线粒体基因的表达，促使细胞通过自噬和谷胱甘肽的合成来维持功能；③ CD8+ T细胞逐渐重塑其转录组和表面表型，并逐渐重建CD8+ T细胞群，CD8+ T细胞的线粒体质量减少，但能够维持能量平衡以维持功能；④ 抑制PGE2信号可促进CD8+ T细胞在肠道中的积累，而干扰自噬和谷胱甘肽会抑制T细胞库的形成；⑤ 这一PGE2-自噬-谷胱甘肽轴揭示了CD8+ T细胞对肠道微环境的代谢适应，促进了对肠道免疫细胞功能的新的理解。 【原文信息】 Prostaglandin E2 controls the metabolic adaptation of T cells to the intestinal microenvironment 2024-01-11 , doi: 10.1038/s41467-024-44689-2 粪菌移植对慢性储袋炎患者菌群和肠黏膜基因表达的影响 Gut Microbes——[12.2] ① 先前进行的通过粪菌移植（FMT）治疗慢性储袋炎的临床试验终点效果不佳，但试验及随访期间收集了大量样本可供调查临床结果与FMT导致的菌群变化间的相关性，以及宿主肠粘膜基因的表达情况；② 基线期患者菌群与健康供体差异显著，经FMT后患者菌群表现出个体异质性和不稳定性，向供体菌群方向改变，但整体相似度不高；③ 基线期抗生素的类型和使用模式显著影响了患者肠腔的菌群组成，导致个体异质性；④ 转录组发现袋内的基因表达从回肠模式向结肠模式转变，其中炎症和免疫系统相关途径上调；⑤ FMT组和安慰剂组的非复发患者预后与基线相比，趋化因子受体CXCR4表达都在第52周下调。 【原文信息】 Microbiota and mucosal gene expression of fecal microbiota transplantation or placebo treated patients with chronic pouchitis 2024-01-12 , doi: 10.1080/19490976.2023.2295445 诺华公布Lutathera一线治疗GEP-NETs 3期临床最新临床数据 ① 1月19日，诺华在2024年ASCO GI年会上，公布了核药Lutathera一线治疗胃肠胰腺神经内分泌肿瘤（GEP-NETs）3期临床NETTER-2研究的最新数据；② 研究结果显示，Lutathera组主要终点mPFS（中位无进展生存期）从8.5个月延长至22.8个月，延长时间近3倍，疾病进展或死亡风险降低72%，ORR（总响应率）高达43%；③ 对于GEP-NETs一线治疗来说，这是首个获得3期临床积极数据的核药疗法，也是该适应证中疗效和安全性最优的治疗方案；④ 诺华预计在今年向欧盟递交Lutathera一线治疗GEP-NETs的上市申请。 【原文信息】 核药新突破：诺华Lutathera一线治疗GEP-NET，PFS延长至3倍 2024-01-21 , 医药笔记 惠升生物治疗糖尿病药物加格列净片获批上市 ① 1月19日，惠升生物宣布其用于治疗2型糖尿病的候选药物加格列净片获批上市；② 加格列净为SGLT-2抑制剂，已获得多国专利权；③ 与传统的降糖药物相比，SGLT-2抑制剂具有药效持久、不易发生低血糖风险、降低糖尿病患者体重等特征优势；④ 临床试验结果显示，加格列净可有效改善血糖控制、降低体重和血压、改善高密度脂蛋白胆固醇和胰岛素敏感性；⑤ 加格列净作为二甲双胍附加疗法治疗单用二甲双胍不能充分控制的中国2型糖尿病患者的3期临床试验结果显示出相似的疗效和安全性。 【原文信息】 惠升生物SGLT-2抑制剂「加格列净片」获批上市 2024-01-19 , 医药魔方Info 声索生物超声内镜类产品获首个FDA 510（k）批准 ① 近日，声索生物科技（上海）有限公司的产品获得FDA的510（k）批准，成为首家将一次性内窥镜用超声探头用于内窥镜用超声诊断设备配套使用的生产厂家；② 该产品是一套完全自主研发，拥有完整核心技术且完全独立工作的产品系统，用于上呼吸道和支气管、消化道与肝胆胰腔内进行超声诊断检查，具有重要的临床价值；③ 该产品解决了临床上超声探头重复使用的问题，提高了产品的便利性和可靠性，减少了交叉感染风险；④ 该产品可兼容更宽频率的超声信号和多种超声探头，公司也即将推出在此临床应用领域外径只有1.1mm最小的超声探头，并正在申请国内的生产许可证。 【原文信息】 突破！声索生物成功获取首个FDA 510(k)批准的内窥镜用超声诊断设备及一次性无菌内窥镜用超声探头认证 2024-01-17 , 动脉网 糖吉医疗宣布“胃转流支架系统”创新产品获批上市 ① 1月17日，糖吉医疗宣布其“胃转流支架系统”创新产品注册申请获中国国家药监局批准；② 胃转流支架系统是一种肠道介入治疗肥胖症的三类创新医疗器械；③ 该产品主要用于隔离食糜与肠道的接触，是一种辅助生活方式管理体重的产品，适用于生活方式调整无效、无创治疗及药物治疗效果不佳的相关肥胖症患者；④ 该产品在不改动胃肠道生理结构的基础上达到类似胃旁路手术的效果，为肥胖症治疗提供新的选择；⑤ 研究历时超过十年，大量的动物实验和人体临床试验为其安全性、有效性提供了更多循证医学证据。 【原文信息】 用于减重！创新三类医疗器械获批上市 2024-01-18 , 医药观澜 蔚蓝生物救必应提取散获得新兽药注册证书 ① 1月20日，青岛蔚蓝生物发布公告称，与其他单位联合申报的“救必应提取散” 获得了农业农村部颁发的《新兽药注册证书》；② 救必应提取散为三类新兽药，具有清热利湿、抗菌消炎的作用，用于治疗鸡大肠杆菌病；③ 鸡大肠杆菌病是由特定血清型致病性大肠杆菌及其毒素引起的一种肠道传染病，大量科学实验表明，救必应水提物及含药血清对致病性大肠杆菌具有较好的抑制杀灭效果。 【原文信息】 蔚蓝生物: 青岛蔚蓝生物股份有限公司关于获得新兽药注册证书的公告 2024-01-20 , 证券之星 感谢本期日报的审核者：章台柳，Zhonghua，圆圈儿，MD，Johnson，好雨，Richard，lxx，Alex Zhang 点击阅读过去10天的日报： 0122 | 国内团队多点开花，十文一览消化道癌症研究新进展 0121 | 补充剂能改善儿童呼吸道感染吗？大型荟萃分析探究竟 0120 | Cell重磅：论菌群的"社会性"及其对健康的影响 0119 | 今日Cell：母乳如何守护宝宝肠道？新机制揭晓 0118 | 刘双江/刘宏伟/姜长涛Nature子刊：小克里斯滕森氏菌生成新型胆汁酸，改善代谢 0117 | 肠炎或促脂肪肝？国内团队揭示肠肝轴机制 0116 | Science子刊揭秘：肠道免疫细胞的全身"旅行"图谱 0115 | 胃肠癌风险有多高？国内团队Lancet子刊重磅发布全球性研究 0114 | 限时进食改善肥胖和代谢，效果如何？29分综述一览最全证据 0113 | 多文聚焦：新方法新技术，助菌群研究更上一层楼

Relapsed or refractory AML patients with TP53 mutation known to have dismal outcomes due to limited effective treatment options 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) Eighth oral presentation of Iomab-B data since announcement of positive Phase 3 SIERRA Results 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). The oral presentation highlighted significantly improved survival in patients with a TP53 mutation receiving Iomab-B. 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. 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. 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. 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. Data highlighted in the ASH oral presentation, which can be accessed on the investor relations page of Actinium's website, included: Overall Survival in Patients with a TP53 Mutation: 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. Response rates by TP53 Mutation Status: 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. 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." 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. Only 1 patient with a TP53 mutation was able to access a BMT on the control arm via conventional care. 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. 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." About Iomab-B and the Pivotal Phase 3 SIERRA Trial 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. 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. 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. 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. 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). 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. 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. 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. 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. 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. 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. 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. About 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. 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 holds more than 220 patents and patent applications. 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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. Investors: investorrelations@actiniumpharma.com 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. Company Codes: AMEX:ATNM