Extrarenal Lupus

→ Kristen Mulholland will take over for the retiring Peter Fasolo as chief human resources officer at J&J on Oct. 1. “Peter has led J&J’s talent strategy for the past 16 years including remarkable leadership through the global pandemic and the separation of our consumer health business,” CEO Joaquin Duato said in a statement . “He leaves a legacy of strong leaders, deep bench strength and an inclusive, caring and patient-focused culture.” Fasolo is a Bristol Myers Squibb HR vet who left J&J to become chief talent officer for KKR , only to return in 2010. Mulholland started at J&J in 2005 and has spent nearly five years as head of human resources, global total rewards & enterprise HR functions. → Just do it: Amgen technology chief David Reese said in a LinkedIn post that the pharma giant has appointed Sean Bruich as SVP of artificial intelligence and data. Bruich moves into the pharma world after an 11-year run with Nike , where he vaulted to global VP, insights, data science & analytics. This is the second high-level AI hire by a major pharma in as many weeks — Pfizer just welcomed Berta Rodriguez-Hervas as its new chief AI and analytics officer. → In its biggest personnel news since Doug Williams ’ resignation , Sana Biotechnology has poached Dhaval Patel from UCB as the Seattle biotech awaits data readouts for its CD19-targeted allogeneic CAR-T therapy in a host of indications. Patel had a 10-year career with Novartis before he held the CSO post at UCB for nearly seven years, and he’ll have the same responsibilities at Sana under CEO Steve Harr . Sana said in its second-quarter update that the goal is to reveal data for SC291 in B cell malignancies — and such autoimmune diseases as lupus nephritis, extrarenal lupus and ANCA-associated vasculitis — sometime this year. “His expertise in immunology and autoimmune diseases make[s] him ideally suited to help advance our clinical pipeline,” Harr said in a statement . → Brian Di Donato , the CFO and head of strategy at Immunocore since May 2020 , is stepping down “at the end of the year” to take the CEO job at an unnamed San Diego biotech. Di Donato was the finance leader for Achillion when Alexion scooped it up for $930 million, and he’s also a board member at Jim Wilson joint iECURE , where ex-Achillion chief Joseph Truitt is CEO. → Telix Pharmaceuticals has separated its business into four separate entities: Telix Therapeutics , Telix Precision Medicine (diagnostics), Telix Lightpoint (medtech, from its acquisition of Lightpoint Medical ) and Telix Manufacturing Solutions . With these changes in place, Telix has tapped Richard Valeix as CEO of Telix Therapeutics, Kevin Richardson as Telix Precision Medicine’s chief executive, and Raphael Ortiz as CEO of Telix International . Christian Behrenbruch ’s title has been slightly modified to group CEO. Telix had hoped to join the Nasdaq in June with an IPO around the $200 million mark, but the Melbourne biotech made a gametime decision to pull those plans . → Cambridge, MA-based neuro player Cognito Therapeutics has promoted Christian Howell to CEO. Brent Vaughan had been running Cognito since 2020 after co-founding and leading the autism diagnostic specialist Cognoa , and he hired Howell as his chief commercial officer last October. Howell had a long career with Medtronic and then joined Aetion , where he was elevated to SVP and general manager of the emerging channels group (medical device, diagnostics, digital health, and government) in April 2023. → Elsewhere, Endo is also losing its president and CEO Blaise Coleman . Board member Scott Hirsch will serve in the interim as the company searches for a permanent successor. Hirsch joined Endo’s board in April, around the same time that the company sued the FDA over its approval of a generic version of Endo’s drug Adrenalin . Hirsch is the former CEO of Solta Medical and also held the roles of president of Ortho Dermatologics and CBO of Bausch Health / Bausch + Lomb . → Thomas Bock has handed in his resignation as CEO of Notable Labs , and CSO Joseph Wagner will take over the top spot on an interim basis. This isn’t uncharted territory for Wagner: He’s the former CEO of Oncocyte (2011-15) and Canadian I/O biotech BriaCell Therapeutics (2015-16). Notable Labs merged with VBL Therapeutics in February 2023 and will start enrolling patients in its Phase 2 study of the ex- Boehringer Ingelheim drug volasertib for acute myeloid leukemia “in the coming months,” the company said in July. → Delfi Diagnostics marked the beginning of the year with a new CEO it hired away from Illumina . Now, the competitor to Grail has brought on Thomas Russo as finance chief. Russo served in the same role at Icosavax and Assembly Biosciences . During his time at Icosavax, Russo helped with the company’s growth until its $838 million upfront acquisition by AstraZeneca . → Marea Therapeutics , the Third Rock upstart led by ex- Graphite Bio CEO Josh Lehrer , has selected Ian Clements as CFO. Clements resigned from the same post at Livmarli maker Mirum Pharmaceuticals in May 2023 after four years overall with the company, and he’s the ex-VP of investor relations for Dermira . Marea launched in June with $190 million in “combined Series A and B” funding, testing an ex-Novartis monoclonal antibody that targets ANGPTL4 in adults with metabolic dysfunction. → With ex- Synlogic CEO Aoife Brennan at the controls, a seemingly rejuvenated Eliem Therapeutics has named Brett Kaplan as COO and Nishi Rampal as SVP, clinical development. Kaplan had been president and chief financial & corporate development officer for epigenetic editing upstart Chroma Medicine , and he was also the finance chief at Prevail until Eli Lilly bought the gene therapy biotech for $1 billion. An Alexion vet, Rampal also handled the role of global development and strategy lead for the neuromyelitis optica spectrum disorder (NMOSD) treatment Uplizna as an executive director with Horizon /Amgen. Eliem’s hunt for strategic alternatives ended with the acquisition of Tenet Medicines and its anti-CD19 antibody budoprutug , once known as TNT119 . → Backed by RA Capital and Forbion , Navigator Medicines disclosed its $100 million Series A this week and the recruitment of Dana McClintock as CMO. McClintock spent six years in the same position at Alladapt Immunotherapeutics and was global head of the Office of I2O Innovation for Genentech . Navigator also said that Forbion general partner Wouter Joustra and RA Capital managing director Andrew Levin have made their way to the board of directors. → Alex Bastian has been named VP, commercial strategy at Swiss-based Memo Therapeutics , reuniting with CEO Erik van den Berg . Toward the end of van den Berg’s tenure as CEO of AM-Pharma , Bastian was the Dutch biotech’s VP, commercial & patient access. He also worked for Galapagos as VP, head of value & market access. → Structure Therapeutics , one of many biotechs developing a GLP-1 drug for obesity, has elected ex- Shire CEO Angus Russell to the board of directors. The 68-year-old Russell has chaired the board at Daxxify maker Revance Therapeutics since 2014 and has a board seat at Lineage Cell Therapeutics . → Ex- Vividion CEO Jeff Hatfield has joined the board of directors at Gate Bioscience , a California drug developer that launched last November with a $60 million Series A from several blue-chip investors. Hatfield chairs the board at Vividion and Rome Therapeutics . → Opna Bio has made room for Inozyme co-founder and former CEO Axel Bolte on the board of directors. The South San Francisco biotech also announced that it had dosed the first patient in a Phase 1 trial of its multiple myeloma candidate OPN-6602 and appointed Myeloma Investment Fund managing director Stephanie Oestreich as a board observer.

TIS2024第四届自免疾病细胞疗法与干细胞疗法论坛重磅来袭，点击图片查看重磅嘉宾，合作详询：王晨 180 1628 8769 （扫码立即报名获取TIS2024免费票） 丨猎药人俱乐部研究团队整理 5月27日，iCell Gene Therapeutics宣布其BCMA与CD19靶向复合嵌合抗原受体-T（BCMA-CD19 cCAR-T）细胞免疫疗法的研究者发起临床试验（IIT）的积极结果，所有接受足量初始剂量cCAR-T治疗的系统性红斑狼疮/狼疮性肾炎患者，在治疗3个月后体内自身抗体呈现阴性，并在随访46个月时，均达到无症状和无药物缓解。 系统性红斑狼疮（SLE）是一种潜在致死的系统性自身免疫性疾病，往往累及全身多系统、多脏器，且治疗后容易复发。据美国红斑狼疮基金会的数据，美国有超过 150 万人受到此病的影响，全球患者数至少为 500 万。弗若斯特沙利文预计在中国在2025年前SLE患者将达到 106.95万人，于 2030 年达到 109.47 万人。 全球SLE市场规模预期由2020年的16亿美元增加至2025年的65亿美元，并预计以21.0%的复合年增长率增长至2030年的169亿美元。其中生物制剂市场规模增长迅速，预计将由2020年的58%增长到80%以上，预计2023年市场规模达142亿美元。 图片来源：宋艳的能量站 CAR-T细胞疗法已经成为治疗B细胞血液癌症的重要手段，它们通过靶向B细胞表面的特定抗原，清除导致血液癌症的B细胞，让不少患者看到了治愈的希望。近年，学术与产业界正逐步探索CAR-T疗法在自身免疫疾病治疗领域的应用潜力。目前，全球有哪些免疫细胞疗法正在开展SLE的治疗研究？哪些企业得到了资本助力？ 01 “新解药”CAR-T疗法有望一次性治愈SLE 3月27日，浙江大学医学院附属儿童医院传来重磅消息：这是国内首个开展CAR-T临床试验的红斑狼疮患儿顺利出院，有望得到彻底治愈！ “此次突破具有重要临床意义，意味着更多难治性红斑狼疮患儿将受惠于医疗科技的进步，得到完全康复的可能。”该临床试验项目负责人，浙大儿院副院长、肾脏泌尿中心主任毛建华教授表示。 这并不是CAR-T疗法应用于SLE治疗领域的第一则好消息。早在2021年，一篇发表在《新英格兰医学》杂志上的临床研究显示，研究团队对1名患有严重系统性红斑狼疮的20岁女性患者进行了 CAR-T细胞治疗，该疗法使得这名难治性患者的病情迅速缓解，且没有明显副作用。该患者也成为了世界上首个接受 CAR-T 细胞治疗的系统性红斑狼疮患者。虽然这为个案，但是这项临床研究结果显示，CAR-T疗法反应迅速，患者症状消退也很迅速。 随后，2022年9月发表在nature medicine 杂志上的一篇研究表明，通过CAR-T细胞疗法治疗5名SLE患者，3个月后所有患者都实现了SLE的缓解，且在长达17个月的随访中没有复发，均实现了无药物缓解。 2024年3月，一篇发表在《新英格兰医学》杂志上的文章，深入分析CAR -T细胞治疗严重自身免疫性疾病的效果。该研究纳入了15名患有严重自身免疫性疾病的患者，包括8名系统性红斑狼疮患者，以CD19  CAR-T细胞作为治疗手段。结果显示，SLE患者的DORIS缓解率显著提高，这意味着CAR-T细胞治疗在严重自身免疫性疾病患者中取得了显著疗效。 除了国外临床研究取得的良好成果，国内多家医院也在CAR-T治疗SLE方面获得好成绩： 2024年4月，武汉协和医院风湿免疫科利用通用型CD19 CAR-γδT治疗严重性SLE患者，三次回输CAR-γδT细胞28天后，患者的SLE疾病活动指数评分降为5分，较回输前明显下降，且期间没有服用任何其他SLE药物。 2024年4月，浙江大学医学院附属第一医院风湿免疫科使用靶向CD19通用型CAR-T细胞治疗难治性SLE患者，经治后患者的SLEDAI评分从治疗前的18分降为0分，并逐渐停用了所有激素和免疫抑制剂。 2024年5月8日，华中首个CAR-T细胞免疫治疗门诊在武汉协和医院正式启用，整合多学科专家资源，为多发性骨髓瘤、淋巴瘤、白血病、SLE等患者提供个体化、精准化的诊疗方案。 系统性红斑狼疮是一种自身免疫性疾病，其特征是 B 细胞功能和自身抗体出现异常，导致免疫系统攻击自身组织引发广泛的炎症和组织损伤。近年来，SLE患者的长期生存虽有所改善，但不可避免的疾病复发及其导致的不可逆的器官损伤仍是SLE患者死亡的重要原因。如何实现减少疾病复发，降低脏器受累，减少并发症，使用最低维持疾病稳定的激素剂量、甚至停用激素，改善难治患者的长期预后仍是当前SLE诊疗中面临的挑战。 细胞治疗的发展为SLE患者带来了一种全新的、安全有效的治疗选择，为SLE患者带来“治愈”的希望，实现长期无药物缓解。  02 全球SLE-免疫细胞疗法研究进展： 监管机构批准多项IND申请，临床管线储备雄厚 目前已有多家公司“嗅到”这一新兴技术的应用潜力，且已经展开布局。经查询医药魔方，目前全球针对SLE治疗的免疫细胞疗法有39款，其中处于临床阶段的有33款，最高研究状态在临床2期。BMS、诺华、阿斯利康等MNC均积极布局，更有细胞疗法明星企业Sana Biotechnology、Nkarta等企业涉足该领域。 将自体 CAR-T 细胞疗法等先进细胞治疗方法应用于自身免疫性疾病领域，已然引起了产业界和学术界极大的兴趣。虽说该研究领域目前尚无产品获批上市，还在探索阶段，但是目前处于临床1期阶段的产品数量高达24款，表明行业雄厚的储备力量，以及极大的研发兴趣。 2023年至2024年间，许多研究机构针对将系统性红斑狼疮和狼疮性肾炎启动新药研究，FDA也批准了多项针对这些适应症的细胞疗法候选药物的IND申请： 2024 年 4 月 8 日，Caribou Biosciences公司的CD19靶向CAR-T疗法CB-010的IND获得美国FDA批准，用于治疗狼疮性肾炎和肾外狼疮。预计该1期临床试验GALLOP将于2024年底前启动。 2024年3月，FDA批准了Synthekine公司SYNCAR-001 联合STK-009的IL-2和CD19 CAR-T的联合疗法的IND申请，用于治疗非肾系统性红斑狼疮和狼疮肾炎患者，该疗法可免于淋巴细胞清除术。 2024年3月，FDA批准了T细胞免疫治疗领域领导者Atara Biotherapeutics同种异体CAR-T疗法ATA3219治疗狼疮性肾炎的IND申请，成为全球首个自免适应症获批临床的通用型CAR-T疗法。这标志着在自身免疫性疾病领域，细胞疗法再次打开了提高产品可及性的大门。 2023年10月，FDA批准了NK细胞疗法明星公司Nkarta的产品CAR-NK细胞疗法NKX019治疗狼疮性肾炎的IND申请。Nkarta的这项多中心、开放标签、剂量递增的临床试验将评估NKX019在难治性LN患者中的安全性和临床活性。Nkarta预计，NKX019 一旦成功上市，这种“现货型”细胞疗法的可用性将减轻患者负担，并消除目前与自体细胞疗法相关的基础设施昂贵和制备周期较长的痛点。 2023年8月，FDA批准了Impact Bio用于治疗活动性难治性系统性红斑狼疮的IND申请。 中国国家药品监督管理局（NMPA）也批准了数款CAR-T细胞疗法用于SLE治疗的IND申请： 2023年4月，药明巨诺宣布瑞基奥仑赛注射液（relma-cel）用于治疗中重度难治性系统性红斑狼疮的IND申请获得中国国家药品监督管理局（NMPA）的默示许可，目前正在进行1期临床试验。 2024年2月，先博生物自主研发的靶向CD19的嵌合抗原受体基因修饰的NK细胞注射液正式获得中国国家药品监督管理局（NMPA）的临床默示许可，适应症为中重度难治性系统性红斑狼疮。这是国内首个通用型NK产品获批SLE适应症IND。 2024年5月，西比曼生物的CD20/BCMA双靶点CAR-T细胞疗法在中国获得了临床试验默示许可，用于治疗中重度难治性系统性红斑狼疮。 全球处于临床1/2期及以上治疗SLE的免疫细胞疗法，不完全统计 药物名称：BCMA-CD19 cCAR-T 靶点：BCMA/CD19 公司：iCell Gene Therapeutics iCell Gene Therapeutics于2024年5月宣布了其BCMA与CD19靶向复合嵌合抗原受体-T（BCMA-CD19 cCAR-T）细胞免疫疗法的研究者发起临床试验（IIT）的积极结果，这项1期临床试验评估了BCMA-CD19 cCAR疗法在13名系统性红斑狼疮患者中的安全性和有效性，其中包括11名患有狼疮性肾炎的患者。 结果显示：所有接受初始剂量3x106 cCAR-T细胞/kg的患者在接受cCAR-T治疗3个月后，所有自身抗体（包括来自长寿浆细胞的抗体）均呈阴性，补体恢复正常水平。这些患者在随访46个月时，均达到无症状和无药物缓解。 该cCAR-T细胞免疫疗法在单一结构中表达两种不同且功能齐全的CAR分子，一种靶向B细胞上的CD19分子，另一种靶向浆细胞上的BCMA分子。其通过消除所有升高的自身抗体，完全重置体液免疫并解决系统性红斑狼疮/狼疮性肾炎的根本原因。 药物名称：Descartes-08 靶点：BCMA 公司：Cartesian Therapeutics Descartes-08是一种处于临床开发阶段的mRNA 细胞疗法候选药物，它通过靶向B细胞成熟抗原（BCMA），清除分泌自身抗体的浆细胞。与传统基于DNA的CAR-T细胞疗法相比，rCAR-T不需要清除已有淋巴细胞的化疗，具有可预测和可控的药代动力学，并避免了基因组整合的风险，因此，相比基于DNA的细胞疗法Descartes-08具有更高的安全性。目前该产品正在进行针对系统性红斑狼疮 、多发性骨髓瘤 、重症肌无力等适应症的临床研究。其中针对系统性红斑狼疮的临床2期研究（NCT06038474），目前已经完成首例入组。 药物名称：IMPT-514 靶点：CD19/CD20 公司：ImmPACT Bio 2023年8月15日，Impact Bio开发的IMPT-514疗法的IND申请获得美国FDA批准，拟用于治疗活动性狼疮肾炎患者的系统性红斑狼疮。IMPT-514采用了强效双特异性CAR和4-1BB共刺激结构域，是首个用于治疗系统性红斑狼疮的双特异性CD19/CD20 CAR- T疗法。在临床前研究中，它能够高效地从狼疮肾炎和系统性红斑狼疮患者体内制造出来，并显示出强效的自体B细胞清除能力和适度的细胞因子特征。 IMPT-514的分化双特异性方法是为了能更广泛地靶向自身反应性B细胞而设计的，增强了CAR-T细胞穿透组织和淋巴器官的特性，能重塑免疫反应来达到持久缓解的效果，因此具有一次性治疗的潜力。 药物名称：BMS-986353 靶点：CD19 公司：BMS BMS-986353是百时美施贵宝公司开发的一款靶向CD19的CAR-T细胞疗法，该疗法目前正在一项多中心、开放标签的1期临床试验中进行测试，以评估其在重症难治性系统性红斑狼疮患者中的耐受性、初步疗效和药代动力学。 03 SLE-免疫细胞疗法：近两年融资/交易总额超过45亿美元 近两年时间内，免疫细胞疗法-SLE相关的交易/融资金额超过45亿美元，多家企业获得资本助力。 Kyverna Therapeutics登陆纳斯达克2024年2月8日，细胞治疗公司Kyverna Therapeutics宣布完成3.19亿美元的超额IPO。该公司专注于开发创新的细胞治疗方法，用于治疗自身免疫性疾病，如类风湿性关节炎等。该公司的研发管线中包括两款下一代靶向CD19的CAR-T细胞疗法，用于治疗B淋巴细胞驱动的自身免疫疾病。此次融资的大部分资金（约 1.5 亿美元）将投入其主要候选产品--CAR-T疗法KYV-101。KYV-101是一款自体CD19靶向CAR-T疗法，用于治疗B细胞驱动的自身免疫疾病，如系统性硬化症、系统性红斑狼疮。其中，系统性红斑狼疮处于临床1期阶段。 阿斯利康收购亘喜生物 2023年12月，阿斯利康已就对亘喜生物收购提案签署最终协议，进一步深化阿斯利康在细胞疗法领域布局。此次拟议收购将为阿斯利康的细胞疗法管线增添GC012F CAR-T细胞疗法。 GC012F是一款处于临床阶段的创新型BCMA/CD19双靶点自体嵌合抗原受体T细胞疗法，目前正在进行针对多发性骨髓瘤、其他多类恶性血液肿瘤以及自身免疫性疾病包括系统性红斑狼疮的临床研究。2023年12月21日，GC012F治疗难治性系统性红斑狼疮的1/2期新药临床试验（IND）申请获中国NMPA正式批准，该研究是一项在中国启动的1/2期临床试验，以进一步评估GC012F针对rSLE患者的安全性和耐受性。此前，该品种已于11月27日获得美国FDA批准开展针对同适应症的1/2期临床试验。此外，一项针对rSLE患者的由研究者发起的临床试验（IIT）正在中国开展。 驯鹿生物和Cabaletta Bio就CD19序列达成全球独家许可协议 2022年10月，驯鹿生物宣布授予Cabaletta其经临床验证的全人源CD19序列的全球独家开发、生产及商业化权利，应用于Cabaletta在自身免疫性疾病领域开发修饰T细胞的产品中。驯鹿生物将有资格获得最多两款产品，累计约为1.62亿美元的首付款以及潜在开发和商业化里程碑付款和销售分成，同时拥有在大中华区使用该许可序列开发Cabaletta产品并将其商品化的优先权。 该授权的CD19序列产品CABA-201目前正在进行系统性红斑狼疮、重症肌无力等适应症的临床研究。2023年4月，Cabaletta Bio CABA-201的IND申请已获得FDA批准，以启动1/2期临床试验，用于治疗活动性狼疮肾炎或无肾脏受累的活动性系统性红斑狼疮。 Cabaletta专注于发现和开发工程T细胞疗法，公司专有的Cabaletta B细胞消融（CABA™）平台旨在通过一次性给药，提供深度、持久和潜在的治愈反应，并有可能消除对慢性免疫抑制疗法的需求。CABA™平台适用于多种自身免疫性疾病，如系统性红斑狼疮、寻常型天疱疮和重症肌无力。 近两年SLE-免疫细胞疗法融资/交易汇总 参考资料： 中国继续医学教育网订阅号，CAR-T细胞疗法治疗系统性红斑狼疮，疗效可期！ 生物世界，CAR-T细胞疗法新突破：成功治疗多个红斑狼疮患者，并实现长期无药物缓解 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 TIS2024第四届免疫细胞疗法与干细胞疗法论坛重磅来袭，合作详询：王晨 180 1628 8769 戳“阅读原文”立即领取限量免费门票！

Continue to advance hypoimmune technology in four trials across seven indications in oncology, B-cell mediated autoimmune diseases, and type 1 diabetes Enrolling patients in the GLEAM trial for SC291 in B-cell mediated autoimmune diseases; expect to report initial clinical data in 2024 Enrolling patients in two oncology trials – ARDENT for SC291 in B-cell malignancies and VIVID for SC262 in relapsed/refractory B-cell malignancies; expect to report additional clinical data in 2024 Enrolling patients in the investigator-sponsored trial with hypoimmune-modified primary islet cells; expect to report initial clinical data in 2024 Publication in Nature Biotechnology shows that healthy transplanted human glial cells replaced diseased glial cell population in a preclinical model Cash position of $251.6 million and expected 2024 operating cash burn below $200 million SEATTLE, Aug. 08, 2024 (GLOBE NEWSWIRE) -- Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on creating and delivering engineered cells as medicines, today reported financial results and business highlights for the second quarter 2024. “The hypoimmune platform addresses one of the fundamental challenges with allogeneic cell transplantation and has the opportunity to impact a broad range of diseases,” said Steve Harr, Sana’s President and Chief Executive Officer. “We have four ongoing trials and are pleased with the progress and encouraged by our learnings in the clinic to-date. We are accelerating investments to build our pivotal-ready supply chain, decrease our reliance on external manufacturing given ongoing geopolitical uncertainty, and increase our clinical trial site footprint globally. We continue the dose escalation phases of our studies, which makes predicting the numbers of patients and release date for data an inexact science, but we look forward to reporting clinical data in each therapeutic area later this year with the goal of an initial understanding of the safety and efficacy profiles.” Recent Corporate Highlights Advancing four clinical programs across seven indications, including an allogeneic CAR T program targeting CD19+ cancers, an allogeneic CAR T program for B-cell mediated autoimmune diseases, an allogeneic CAR T program for cancer patients that have failed a CD19-targeted therapy, and a gene-modified primary islet cell therapy in type 1 diabetes: Oncology – The ARDENT trial evaluates SC291, a hypoimmune (HIP)-modified CD19-directed allogeneic CAR T therapy, in patients with B-cell malignancies. Early SC291 data from the ongoing ARDENT trial suggest the ability to dose safely, the desired immune evasion profile, and early clinical efficacy. The VIVID trial evaluates SC262, a HIP-modified CD22-directed allogeneic CAR T therapy, in patients with relapsed or refractory B-cell malignancies who have received prior CD19-directed CAR T therapy. Sana is enrolling patients in both studies and expects to share data in 2024.B-cell Mediated Autoimmune Diseases – The GLEAM trial evaluates SC291 in patients with B-cell mediated autoimmune diseases including lupus nephritis, extrarenal lupus, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Sana is enrolling patients in this study and expects to share initial data in 2024.Type 1 Diabetes – UP421 is a primary human HIP-modified pancreatic islet cell therapy for patients with type 1 diabetes. The goal of this investigator-sponsored trial (IST) is to understand immune evasion, islet cell survival, and beta cell function, as measured by C-peptide production, of HIP-modified pancreatic islet cells in type 1 diabetics without any immunosuppression. Initial screening took longer than anticipated, and after a protocol amendment to expand the eligible patient pool, multiple patients are now enrolled and awaiting donor availability. Sana awaits initial patient dosing at Uppsala University Hospital and expects to share initial data in 2024. Published preclinical data in Nature Biotechnology showing that healthy transplanted human glial progenitor cells replaced diseased glial cell population in a preclinical model: In the study, human glial chimeric mice were used to model the impact of competition between healthy and diseased human glia in vivo. When wild-type (WT) healthy human glial progenitor cells (hGPCs) were transplanted into adult mice that had been neonatally chimerized with mutant Huntingtin (mHTT)-expressing hGPCs, the healthy cells outcompeted and ultimately eliminated diseased glia, repopulating the brain with the healthy cells.These data establish additional proof-of-concept for the development of SC379, Sana’s pluripotent stem cell (PSC)-derived glial progenitor cell (GPC) product candidate, as a potential therapy to deliver healthy allogeneic GPCs to patients with certain central nervous system disorders. Second Quarter 2024 Financial Results GAAP Results Cash Position: Cash, cash equivalents, and marketable securities as of June 30, 2024 were $251.6 million compared to $205.2 million as of December 31, 2023. The increase of $46.4 million was primarily driven by net proceeds from equity financings of $181.0 million, proceeds from stock option exercises and the employee stock purchase plan of $8.4 million, and proceeds of $7.6 million from a loan to fund tenant improvements for our manufacturing facility in Bothell, Washington during the six months ended June 30, 2024, partially offset by cash used in operations of $124.2 million and cash used for the purchase of property and equipment of $28.9 million.Research and Development Expenses: For the three and six months ended June 30, 2024, research and development expenses, inclusive of non-cash expenses, were $60.9 million and $117.3 million, respectively, compared to $73.0 million and $140.2 million for the same periods in 2023. The decreases of $12.1 million and $22.9 million for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023 were primarily due to lower personnel-related and laboratory costs due to a decrease in headcount and decreased research costs related to the strategic repositioning in the fourth quarter of 2023, lower costs for third-party manufacturing at contract development and manufacturing organizations, and a decline in facility and other allocated costs. These decreases were partially offset by increased clinical development costs and an increase in costs for the acceleration of internal manufacturing capabilities, further de-risking of the supply chain. Research and development expenses include non-cash stock-based compensation of $7.1 million and $13.0 million, respectively, for the three and six months ended June 30, 2024 and $6.7 million and $12.7 million, for the same periods in 2023.Research and Development Related Success Payments and Contingent Consideration: For the three and six months ended June 30, 2024, Sana recognized a non-cash gain of $27.9 million and a non-cash expense of $10.1 million, respectively, in connection with the change in the estimated fair value of the success payment liabilities and contingent consideration in aggregate, compared to non-cash expenses of $26.7 million and $26.8 million for the same periods in 2023. The value of these potential liabilities fluctuate significantly with changes in Sana’s market capitalization and stock price.General and Administrative Expenses: General and administrative expenses for the three and six months ended June 30, 2024, inclusive of non-cash expenses, were $16.4 million and $32.7 million, respectively, compared to $16.6 million and $33.3 million for the same periods in 2023. The decrease of $0.2 million for the three months ended June 30, 2024 compared to the same period in 2023 was primarily due to a decrease in costs related to Sana’s previously planned manufacturing facility in Fremont, California, lower personnel-related costs due to a decrease in headcount related to the strategic repositioning in the fourth quarter of 2023, and a decrease in legal fees. These decreases were partially offset by an increase in non-cash stock-based compensation and consulting fees. The decrease of $0.6 million for the six months ended June 30, 2024 compared to the same period in 2023 was primarily due to a decrease in costs related to Sana’s previously planned manufacturing facility in Fremont, California and lower personnel-related costs due to a decrease in headcount related to the strategic repositioning in the fourth quarter of 2023. These decreases were partially offset by an increase in non-cash stock-based compensation, legal fees, and consulting costs.Net Loss: Net loss for the three and six months ended June 30, 2024 was $50.3 million, or $0.21 per share, and $157.8 million, or $0.70 per share, respectively, compared to $114.0 million, or $0.59 per share, and $196.1 million, or $1.02 per share for the same periods in 2023. Non-GAAP Measures Non-GAAP Operating Cash Burn: Non-GAAP operating cash burn for the six months ended June 30, 2024 was $104.6 million compared to $136.5 million for the same period in 2023. Non-GAAP operating cash burn is the decrease in cash, cash equivalents, and marketable securities, excluding cash inflows from financing activities, cash outflows from business development, non-recurring items, and the purchase of property and equipment.Non-GAAP Net Loss: Non-GAAP net loss for the three and six months ended June 30, 2024 was $74.2 million, or $0.32 per share, and $143.6 million or $0.64 per share, respectively, compared to $87.3 million, or $0.45 per share, and $169.3 million, or $0.88 per share for the same periods in 2023. Non-GAAP net loss excludes non-cash expenses and gains related to the change in the estimated fair value of contingent consideration and success payment liabilities, and the impairment of an other asset. A discussion of non-GAAP measures, including a reconciliation of GAAP and non-GAAP measures, is presented below under “Non-GAAP Financial Measures.” About Sana Sana Biotechnology, Inc. is focused on creating and delivering engineered cells as medicines for patients. We share a vision of repairing and controlling genes, replacing missing or damaged cells, and making our therapies broadly available to patients. We are a passionate group of people working together to create an enduring company that changes how the world treats disease. Sana has operations in Seattle, Cambridge, South San Francisco, and Rochester. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements about Sana Biotechnology, Inc. (the “Company,” “we,” “us,” or “our”) within the meaning of the federal securities laws, including those related to the company’s vision, progress, and business plans; expectations for its development programs, product candidates and technology platforms, including its preclinical, clinical and regulatory development plans and timing expectations; expectations regarding the timing, substance, significance, and impact of data from clinical trials of the Company’s product candidates and an IST utilizing HIP-modified primary islet cells in patients with type 1 diabetes; the potential impact of accelerating our investments on our ability to decrease our reliance on external manufacturing, build out our pivotal-ready supply chain, and increase our clinical site footprint globally for our trials; expectations regarding the Company’s 2024 operating cash burn; the potential ability to dose safely, achieve the desired immune evasion profile, and achieve clinical efficacy with SC291 in patients with B-cell malignancies; and the potential of SC379 as a potential therapy to deliver healthy allogeneic GPCs to patients with certain central nervous system disorders. All statements other than statements of historical facts contained in this press release, including, among others, statements regarding the Company’s strategy, expectations, cash runway and future financial condition, future operations, and prospects, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results to vary materially, including, among others, the risks inherent in drug development such as those associated with the initiation, cost, timing, progress and results of the Company’s current and future research and development programs, preclinical and clinical trials, as well as economic, market, and social disruptions. For a detailed discussion of the risk factors that could affect the Company’s actual results, please refer to the risk factors identified in the Company’s Securities and Exchange Commission (SEC) reports, including but not limited to its Quarterly Report on Form 10-Q dated August 8, 2024. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason. Investor Relations & Media:Nicole Keithinvestor.relations@sana.commedia@sana.com Sana Biotechnology, Inc.Unaudited Selected Consolidated Balance Sheet Data June 30, 2024 December 31, 2023 (in thousands) Cash, cash equivalents, and marketable securities$251,643 $205,195 Total assets 618,667 565,299 Contingent consideration 111,621 109,606 Success payment liabilities 20,847 12,799 Total liabilities 279,018 277,793 Total stockholders' equity 339,649 287,506 Sana Biotechnology, Inc.Unaudited Consolidated Statements of Operations Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 (in thousands, except per share data) Operating expenses: Research and development$60,874 $73,044 $117,322 $140,210 Research and development related success payments and contingent consideration (27,944) 26,679 10,063 26,799 General and administrative 16,442 16,566 32,711 33,332 Total operating expenses 49,372 116,289 160,096 200,341 Loss from operations (49,372) (116,289) (160,096) (200,341)Interest income, net 3,202 2,374 6,236 4,350 Other expense, net (4,121) (84) (3,906) (131)Net loss$(50,291) $(113,999) $(157,766) $(196,122)Net loss per common share – basic and diluted$(0.21) $(0.59) $(0.70) $(1.02)Weighted-average number of common shares – basic and diluted 234,440 192,540 225,872 191,888 Sana Biotechnology, Inc.Changes in the Estimated Fair Value of Success Payments and Contingent Consideration Success PaymentLiability(1) ContingentConsideration(2) Total Success Payment Liability and Contingent Consideration (in thousands) Liability balance as of December 31, 2023$12,799 $109,606 $122,405 Changes in fair value – expense 32,623 5,384 38,007 Liability balance as of March 31, 2024 45,422 114,990 160,412 Changes in fair value – gain (24,575) (3,369) (27,944)Liability balance as of June 30, 2024$20,847 $111,621 $132,468 Total change in fair value for the six months ended June 30, 2024$8,048 $2,015 $10,063 (1) Cobalt Biomedicine, Inc. (Cobalt) and the Presidents of Harvard College (Harvard) are entitled to success payments pursuant to the terms and conditions of their respective agreements. The success payments are recorded at fair value and remeasured at each reporting period with changes in the estimated fair value recorded in research and development related success payments and contingent consideration on the statement of operations. (2) Cobalt is entitled to contingent consideration upon the achievement of certain milestones pursuant to the terms and conditions of the agreement. Contingent consideration is recorded at fair value and remeasured at each reporting period with changes in the estimated fair value recorded in research and development related success payments and contingent consideration on the statement of operations. Non-GAAP Financial Measures To supplement the financial results presented in accordance with generally accepted accounting principles in the United States (GAAP), Sana uses certain non-GAAP financial measures to evaluate its business. Sana’s management believes that these non-GAAP financial measures are helpful in understanding Sana’s financial performance and potential future results, as well as providing comparability to peer companies and period over period. In particular, Sana’s management utilizes non-GAAP operating cash burn, non-GAAP research and development expense and non-GAAP net loss and net loss per share. Sana believes the presentation of these non-GAAP measures provides management and investors greater visibility into the company’s actual ongoing costs to operate its business, including actual research and development costs unaffected by non-cash valuation changes and certain one-time expenses for acquiring technology, as well as facilitating a more meaningful comparison of period-to-period activity. Sana excludes these items because they are highly variable from period to period and, in respect of the non-cash expenses, provides investors with insight into the actual cash investment in the development of its therapeutic programs and platform technologies. These are not meant to be considered in isolation or as a substitute for comparable GAAP measures and should be read in conjunction with Sana’s financial statements prepared in accordance with GAAP. These non-GAAP measures differ from GAAP measures with the same captions, may be different from non-GAAP financial measures with the same or similar captions that are used by other companies, and do not reflect a comprehensive system of accounting. Sana’s management uses these supplemental non-GAAP financial measures internally to understand, manage, and evaluate Sana’s business and make operating decisions. In addition, Sana’s management believes that the presentation of these non-GAAP financial measures is useful to investors because they enhance the ability of investors to compare Sana’s results from period to period and allows for greater transparency with respect to key financial metrics Sana uses in making operating decisions. The following are reconciliations of GAAP to non-GAAP financial measures: Sana Biotechnology, Inc.Unaudited Reconciliation of Change in Cash, Cash Equivalents, and Marketable Securities toNon-GAAP Operating Cash Burn Six Months Ended June 30, 2024 2023 (in thousands) Beginning cash, cash equivalents, and marketable securities$205,195 $434,014 Ending cash, cash equivalents, and marketable securities 251,643 325,915 Change in cash, cash equivalents, and marketable securities 46,448 (108,099)Cash paid to purchase property and equipment 28,901 3,753 Change in cash, cash equivalents, and marketable securities, excluding capital expenditures 75,349 (104,346)Adjustments: Net proceeds from issuance of common stock (181,029) (27,014)Cash paid for personnel-related costs related to portfolio prioritizations 1,110 1,881 Cash received in connection with the Coronavirus Aid, Relief, and Economic Security Act - (7,063)Operating cash burn – Non-GAAP$(104,570) $(136,542) Sana Biotechnology, Inc.Unaudited Reconciliation of GAAP to Non-GAAP Net Loss and Net Loss Per Share Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 (in thousands, except per share data) Net loss – GAAP$(50,291) $(113,999) $(157,766) $(196,122)Adjustments: Change in the estimated fair value of the success payment liabilities(1) (24,575) 20,784 8,048 15,444 Change in the estimated fair value of contingent consideration(2) (3,369) 5,895 2,015 11,355 Impairment of other asset 4,069 - 4,069 - Net loss – Non-GAAP$(74,166) $(87,320) $(143,634) $(169,323)Net loss per share – GAAP$(0.21) $(0.59) $(0.70) $(1.02)Adjustments: Change in the estimated fair value of the success payment liabilities(1) (0.11) 0.11 0.03 0.08 Change in the estimated fair value of contingent consideration(2) (0.02) 0.03 0.01 0.06 Impairment of other asset 0.02 - 0.02 - Net loss per share – Non-GAAP$(0.32) $(0.45) $(0.64) $(0.88)Weighted-average shares outstanding – basic and diluted 234,440 192,540 225,872 191,888 (1) For the three months ended June 30, 2024, the gain related to the Cobalt success payment liability was $20.7 million compared to an expense of $18.5 million for the same period in 2023. For the six months ended June 30, 2024, the expense related to the Cobalt success payment liability was $7.2 million compared to an expense of $13.7 million for the same period in 2023. For the three months ended June 30, 2024, the gain related to the Harvard success payment liabilities was $3.9 million compared to an expense of $2.3 million for the same period in 2023. For the six months ended June 30, 2024, the expense related to the Harvard success payment liabilities was $0.8 million compared to an expense of $1.7 million for the same period in 2023.(2) The contingent consideration is in connection with the acquisition of Cobalt.