Precision BioSciences, Inc.

-01-引言目前，使用嵌合抗原受体（CAR）T细胞进行治疗已成为治疗某些血液系统肿瘤患者的有力工具。然而，所有FDA批准的CAR-T细胞疗法均基于从患者身上分离的自体T细胞，尽管有显著的临床效果，该策略仍有几个重要的局限性，即治疗成本非常高，个别生产过程可能存在问题。与使用自体CAR-T细胞的治疗相比，由同种异体供体材料产生的CAR-T细胞具有三个主要优势。首先，根据个体患者的既定治疗方案，可以提前生产同种异体CAR-T细胞，并毫不延迟地交付。其次，异基因供体来源的T细胞不会暴露于多轮抗白血病治疗中，因此它们更容易接受体外操作。第三，一小部分患者最终可能永远无法获得质量良好、数量有治疗意义的自体CAR-T细胞产品。目前，已有多项异基因CAR-T细胞疗法进入临床阶段，其中一些临床试验展现出良好的应用前景，可能为更多更广泛的患者带来福音。-02-一、异基因CAR-T细胞的制造同种异体CAR-T细胞可以并且应该代替自体CAR-T细胞或与自体CAR-T细胞结合使用时，有几种情况：i）有阻碍自体产品制造的物流问题；ii）制造失败，其中同种异体产品可以替代自体产品，而不会延迟计划的输注；iii）当自体产品在患者体内无法扩增时，输注同种异体CAR-T细胞产品；iv）由于患者的T细胞数量较低和/或疾病进展迅速，无法预先制造自体CAR-T细胞产品；v） 异基因CAR-T细胞产品通过设计成为造血干细胞移植的桥梁。尽管使用同种异体CAR-T细胞进行治疗有许多优点，但这种技术有两个主要缺点。首先，受者的细胞对所给予CAR-T细胞的天然T细胞受体（TCR）可能诱导其激活并导致急性移植物抗宿主病（GvHD）。其次，CAR-T细胞对宿主免疫系统是外来的，这可能会导致它们迅速从循环中清除。因此，异基因CAR-T细胞的制造主要是通过各种手段破坏CAR-T细胞的TCR和MHC-1分子。破坏TCR可以通过三种不同的方式进行：抑制蛋白的表达；通过使用TALENS或CRISPR/Cas9敲除编码TCR链的基因；通过shRNA介导mRNA的沉默。上面的方法均不能从细胞群中100%的去除TCR。因此，剩余TCR+细胞的额外消耗是制造同种异体CAR-T细胞的一个重要部分，这在很大程度上决定了GvHD的发生和治疗效果。最先进的消除TCR +细胞的方法是基于CliniMACS™的装置。简言之，在引入CAR和TCR消除后，首先用生物素化的抗TCR抗体孵育T细胞，然后用与磁性微球结合的抗生物素抗体孵育T细胞。随后，残留的TCR+细胞被CliniMACS清除。此外，为了增加异基因CAR-T细胞的持久性，可以考虑通过基因敲除免疫排斥的关键介质MHC-I分子，这可以通过破坏编码β-微球蛋白的基因来实现。-03- 二、异基因CAR细胞的来源根据临床经验，同种异体CAR-T细胞清除肿瘤细胞的能力取决于初始扩增、持续时间、GvHD的发生以及宿主免疫系统排斥这些细胞的能力。在制定管理异基因CAR-T细胞的策略时，可以选择不同来源的细胞及细胞亚群。αβT细胞用于制造同种异体CAR-T细胞的T细胞主要来源于外周血单个核细胞，尤其是具有由α和β链组成的TCR的细胞，其构成健康供体循环T细胞的约90%。由于αβT细胞在外周血中的相对丰度和快速增殖的能力，它是制造同种异体CAR-T细胞的一个有吸引力的靶点。然而，该细胞亚群在急性和慢性GvHD的发病机制中起主要作用。因此，需要通过基因编辑手段破坏TCR，以减少发生GvHD的风险。病毒特异性T细胞除了基因编辑方法外，减轻GvHD的策略之一是使用基于病毒特异性T细胞的CAR-T细胞，这些细胞结合了CAR的抗肿瘤活性和降低GvHD风险。GvHD风险与TCR多样性相对应，因此，输注病毒特异性记忆T细胞后GvHD减少可能是由于病毒特异性记忆T细胞中TCR的功能受到限制。此外，这种策略的一个可能的不足是初始病毒特异性记忆T细胞的数量较低。γδT细胞供体来源的γδT细胞通过利用其固有受体以不依赖于MHC分子的方式识别多种肿瘤抗原，并且可以在没有TCR清除的同种异体环境中应用。此外，一旦激活，它们可以通过促进其他免疫细胞的功能，进而产生进一步的适应性免疫反应。诱导多能干细胞（iPSC）诱导多能干细胞应用于CAR-T具有显著的优势：iPSC具有自我更新能力，能够在体外长期培养，可以在体外进行各种复杂和精确的基因改造；iPSC具有分化为人体所有细胞类型的能力，可产生大量的功能性T细胞。尽管存在一些限制，但IPSC仍具有均匀和大规模生产的CAR-T细胞的潜力。NK细胞异基因NK细胞对于过继性细胞治疗（ACT）是相当安全的，因为它们通常不介导发生GVHD。此外，NK细胞仅分泌少量IFN-γ和GM-CSF，不产生启动CRS的IL-1和IL-6。其次，除了通过单链抗体识别肿瘤表面抗原来抑制癌细胞外，NK细胞还可以通过多种受体识别各种配体来抑制癌细胞，例如自然细胞毒性受体（NKp46、NKp44和NKp30）、NKG2D和DNAM-1（CD226）。最后，NK细胞在临床样本中非常丰富，可以从外周血（PB）、脐带血（UCB）、人类胚胎干细胞（HESC）、iPSC甚至NK-92细胞系中产生。-04-三、异基因CAR细胞治疗的临床试验ALLO-715抗BCMACAR-T细胞（NCT04093596）这是一项1期临床试验，招募患有r/r多发性骨髓瘤患者。截至2020年10月，共有31名患者纳入安全人群。疗效人群包括26名患者，分为四个剂量水平的细胞（40、160、320和480×106），平均随访时间为3.2个月。ALLO-715的CAR-T细胞受体包括具有4-1BB共刺激结构域的单链可变抗BCMA片段。为了防止移植物排斥反应，并在不影响ALLO-715 CAR-T细胞的情况下允许选择性淋巴细胞耗竭，引入了CD52和TRAC的KOs。26名患者的所有剂量组和淋巴清除方案的总有效率（ORR）为42%（11/26）。在接受320×106细胞ALLO-715治疗的10名患者中观察到了优越的抗癌活性。对于该队列，ORR为60%（6/10），其中4名患者（40%）观察到非常好的部分响应。在45%（14/31）患者中报告了CRS。一名患者在ALLO-715输注后一天出现非中性粒细胞减少性发热和多灶性肺炎，一次5级发作导致呼吸衰竭和死亡。研究认为这一事件与进行性骨髓瘤以及环磷酰胺和ALLO-647预处理方案有关。研究报告，42%（13/31）患者在治疗期间出现了感染性疾病，其中13%的患者出现了3级感染。未观察到GvHD或ICAN病例。ALLO-501抗CD19CAR-T细胞（NCT03939026）ALLO-501是一项针对复发/难治性非霍奇金淋巴瘤（r/r NHL）患者的I期临床试验，ALLO-501CAR-T基于小鼠CD19特异性单链抗体（4G7）。截至2021年4月19日，41例患者接受了ALLO-501治疗，有效人群包括32例患者，共三个剂量组（40, 120和360×106）。治疗包括先前的淋巴清除，包括使用氟达拉滨加环磷酰胺和ALLO-647。结果显示，整体ORR为75%（24/32），50%（16/32）完全缓解（CR）。研究报告11例（27%）患者出现轻度至中度CRS，1例（2%）出现3级神经毒性，登记患者中无GvHD。感染率为61%（25/41），与使用自体CAR-T细胞的试验中观察到的感染率相似。UCART19抗CD19CAR-T细胞UCART19是一种基于慢病毒转导CAR19并使用TRAC/CD52特异性TALENs的CAR-T细胞产品。TALENs用于在编码TCR和CD52α恒定链的基因中引入KOs，以最小化GvHD风险。用磁珠去除残留的TCR+细胞后，只有0.7%的细胞具有可检测的细胞表面TCR。在7名儿童的PALL试验和14名成人的CALM试验中，评估了UCART19的安全性和有效性。患者必须有CD19+B细胞急性淋巴细胞白血病的证据，在UCART19输注前，所有患者均进行了淋巴清除：17名患者（81%）给予了氟达拉滨、环磷酰胺和alemtuzumab，4名患者（19%）给予了氟达拉滨和环磷酰胺。PALL试验中的儿童接受UCART19（1.1–2.3×106/kg），CALM试验包括剂量递增阶段（6×106细胞、6–8×107细胞或1.8–2.4×108细胞）。全体患者和接受含alemtuzumab的淋巴清除患者的ORR分别为67%（14/21）和82%（14/17）。14名患者中有10名（71%）获得完全缓解，并继续进行异基因造血干细胞移植（HSCT）。研究报告，在2019年8月的数据截止日期，14名获得响应的患者中有10名（71%）随后复发或死亡。6个月时无进展生存率为27%。UCART19观察到的副作用似乎与报道的自体抗D19 CAR-T细胞的副作用相似。CRS是UCART19治疗最常见的不良事件（91%的患者），等级≥3的CRS出现在三名患者中。只有两名患者（10%）在UCART19输注后出现1级GvHD。CTX110抗CD19CAR-T细胞（NCT04035434）UCART19和其他CAR-T细胞使用随机整合的病毒将编码CAR结构的基因传递给T细胞DNA。CRISPR Therapeutics使用CRISPR/Cas9将CAR结构精确插入TRAC位点。CTX110是使用该技术靶向CD19+B细胞恶性肿瘤的CAR-T细胞。目前，正在进行的1期CARBON临床试验评估了CTX110在11例患有r/r NHL患者中的安全性和有效性。11名患者在使用氟达拉滨和环磷酰胺进行淋巴细胞清除后，以四种剂量水平（30、100、300或600×106）输注CTX110细胞。结果显示，在30–300×106 剂量组中，没报告有GvHD病例。其它不良反应包括3例等级≤2的CRS（30%）和1例2级ICAN（10%）。36%（4/11）的患者获得CR。PBCAR0191抗CD19CAR-T细胞（NCT03666000）Precision BioSciences公司的同种异体产品PBCAR0191使用了基于I-CreI归巢内切酶的通用基因组编辑平台ARCUS，将CD19特异性CAR插入TRAC位点。I期临床研究的初步数据显示， 27例患者（16例为r/r NHL，11例为r/r B-ALL）中，所有剂量组的ORR和CR分别为55%（15/27）和37%（10/27）。最近，另一项研究报告了PBCAR0191高剂量（3×106个细胞）并伴有增强淋巴清除（氟达拉滨加环磷酰胺）的患者队列的临床结果。试验共纳入21例患者，包括16例非霍奇金淋巴瘤患者和5例B-ALL患者，对其中13例NHL患者和5例ALL患者的治疗效果进行了评估。结果显示，ORR为83%（15/18），CR为66%（12/18）。大多数不良事件是轻微的，在1例NHL患者中观察到ICANS 3级，在31%（5/16）NHL患者中观察到3级感染，在80%（4/5）B-ALL患者中观察到3级感染，未观察到GvHD的证据。CYAD-101（NCT03692429）CYAD-101是由Celyad Oncology开发的一款基于NKG2D受体和TCR抑制分子（TIM）的非基因编辑同种异体CAR-T细胞。NKG2D受体可以识别表达在大多数实体瘤和血癌细胞表面的8种不同的配体，使其可以同时靶向多种不同的癌症；TIM旨在消除负责GvHD的免疫反应，从而避免GvHD。CYAD-101在不可切除转移性结直肠癌患者的alloSHRINK I期研究中进行了评估。在标准预处理化疗（FOLFOX）后，15名患者接受三种剂量水平中的一种（每次输注1×108、3×108或1×109细胞）。研究没有报告剂量限制性毒性或GvHD。在15名患者中，2名（13%）患者获得部分缓解（PR），9名（60%）患者病情稳定（SD）。CIK抗CD19细胞（NCT03389035）有研究提出了一种基于“睡美人”转座子系统的异基因CAR-T细胞，用CARs产生CIK细胞。根据CIK细胞方案，刺激细胞分化为记忆T细胞亚群。在多中心临床研究中（NCT03389035），对13例HSCT后复发的B-ALL患者使用CARCIK-CD19细胞。研究没有报告ICANS或GvHD病例，唯一的严重不良事件是接受最高剂量治疗患者出现的两例1级和2级CRS。61.5%的患者出现完全缓解，而在接受两种最高剂量的6名患者中，85.7%的患者出现完全缓解。ATA188（NCT03283826）ATA188是一款由Atara公司开发的异基因EBV特异性T细胞免疫疗法。在针对多发性硬化症的的I期试验中评估了ATA188这种EBV特异性T细胞亚群的初步疗效和安全性。结果显示，在输注ATA188细胞后无GvHD或CRS的记录，进行性多发性硬化症患者对ATA188耐受性良好，未见剂量限制性毒性。Vγ9Vδ2 T细胞异基因Vγ9Vδ2 T细胞治疗在晚期恶性肝癌（NCT03183232）、肺癌（NCT03183219）、胰腺癌（NCT03183206）或乳腺癌（NCT03180437）中进行了临床评估。输注异基因Vγ9Vδ2 T细胞后未报告重大不良事件（CRS、GvHD）。NK细胞关于工程化异基因CAR-NK细胞，有研究报告了一期和二期试验的结果，其中11名r/r NHL或CLL患者接受了来自脐血的HLA不匹配的抗CD19 CAR-NK细胞治疗。研究没有报告CRS、ICAN和GvHD，所有患者都有可逆的血液毒性事件，主要与淋巴细胞清除有关。在平均13.8个月的随访中，7名患者（64%）完全缓解。在唯一完成的针对AML患者靶向CD33的CAR-NK-92试验中，在输注CD33-CAR NK-92细胞后仅有两例I级CRS，无GvHD病例。然而，不幸的是，两名患者复发，一名患者对治疗无反应。-05-结语显然，使用来自健康捐赠者的CAR-T细胞产品是有利的，因为它对患者的免疫状态依赖性较小，更标准化，并且由于生产成本较低，大大扩大了患者获得治疗的机会。此外，还必须考虑到，在疾病迅速发展时，自体CAR-T细胞制造所需的时间是一个关键因素；另外，一小部分患者可能永远无法获得数量、质量良好的自体CAR-T细胞。然而，异基因CAR-T细胞可能导致GvHD，并且自身可能被受体的免疫系统排斥。此外，与自体CAR-T细胞相比，同种异体CAR-T细胞的疗效和应答率较低，这在很大程度上归因于其较低的持久性。但从长远来看，这也可能是一种安全优势。目前，多项研究正在临床中检验不同靶点和不同技术平台开发的异基因CAR-T细胞疗法，随着现有技术的进一步成熟和新技术的开发，相信异基因CAR-T细胞疗法终将会使更多的肿瘤患者受益。参考资料：1.Strategies to Circumvent the Side-Effects of Immunotherapy Using Allogeneic CAR-T Cells and Boost Its Efficacy: Resultsof Recent Clinical Trials. Front Immunol. 2021; 12: 780145.公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

DUBLIN--(BUSINESS WIRE)--The "CAR-T Funding Report - Venture Capital, IPOs, Licensing Deals, Collaborations, and M&A Transactions, 2025" has been added to ResearchAndMarkets.com's offering. In recent years, the CAR-T industry has experienced a remarkable surge in funding. CAR-T therapies have catalyzed a funding boom, with start-ups being richly supported by investors and large pharmaceutical companies eager to penetrate this burgeoning area of regenerative medicine. Globally, over 170 companies are actively developing CAR-T products, with 1,944 therapies in various development stages. Companies have engaged in approximately 110 collaboration agreements to advance their CAR-T candidates, with only 38 of these deals publicly disclosing a collective value of $23.58 billion. The estimated value for all collaborations could ascend to $67.9 billion. This industry garners significant interest from venture capitalists worldwide. Since 2014, 89 CAR-T companies have raised $7.7 billion in venture capital, paving the way for technological advancement and diversification into therapies for hematological and other cancers. Despite a slow IPO market in 2024, exemplified by Kyverna Therapeutics' $319 million raise, 42 companies have gone public since 2014, amassing $6.4 billion to enhance their platforms and strategies. Currently, the industry boasts 72,418 patent records, with 452 patents granted, highlighting that major pharmaceutical companies are eager to license these innovations. Over ten years, 91 CAR-T licensing deals have reached a valuation of $6.3 billion, a figure expected to rise dramatically over the next decade. The year 2023 witnessed a resurgence in dealmaking, although 2024 saw a dip in mergers and acquisitions (M&A) with merely two consummated deals. Significant M&A activity may not return in 2025. However, further deals are anticipated as pharmaceutical companies seek to invest their reserves. M&A deals have played a pivotal role in industry financing, generating a total of $97.4 billion. Across varying deal types-including IPOs, licensing, collaborations, and M&A transactions-the CAR-T sector has amassed over $141.2 billion. With many deals undisclosed, estimates suggest the industry financing might soar to $281.7 billion. Globally Approved CAR-T Therapies Since 2017, 13 CAR-T cell therapies have been commercialized across global healthcare markets. Seven therapies received U.S. FDA approval, with subsequent global endorsements. China's National Medical Products Administration has validated four therapies, while India's Central Drugs Standard Control Organisation approved two. The existing 13 therapies are exclusively for blood cancer treatment, serving less than 5% of global cancer patients. There are currently around 1,944 clinical trials aimed at blood and solid tumors, driven by an impressive 90% remission rate in approved therapies. CAR-T Market Overview The comprehensive 220-page CAR-T market funding report reviews global investment trends within the sector, detailing financing rounds, IPOs, M&A, strategic alliances, and profiling 78 leading competitors. Benefits of this Report: To summarize, CAR-T entities, from innovative start-ups to extensive enterprises, have engaged in numerous financial endeavors worth hundreds of billions. This report reveals critical insights into the financial dynamics shaping the industry, showcasing capital allocations and strategic opportunities for growth. Key Topics Covered: Companies Featured A2 Biotherapeutics Adicet Bio AffyImmune Therapeutics Allogene Therapeutics Arcellx Arsenal Biosciences Artiva Biotherapeutics Atara Biotherapeutics Autolus Therapeutics AvenCell Therapeutics Bellicum Pharmaceuticals BioNTech Biosceptre Cabaletta Bio Capstan Therapeutics Cargo Therapeutics Caribou Biosciences Carina Biotech CARsgen Therapeutics Cellares Cellular Biomedicine Group Celularity Celyad Oncology Clade Therapeutics Coeptis Therapeutics CRISPR Therapeutics Currus Biologics Dynamic Cell Therapies EXUMA Biotech Gracell Biotechnologies IASO Biotherapeutics ImmPACT Bio Immuneel Therapeutics Inceptor Bio Interius BioTherapeutics Juno Therapeutics Juventas Cell Therapy JW Therapeutics Kyverna Therapeutics Legend Biotech Leman Biotech Leucid Bio Limula March Biosciences Mnemo Therapeutics MPC Therapeutics Mustang Bio Noile-Immune Biotech OneChain Immunotherapeutics OriCell Therapeutics PeproMene Bio Poseida Therapeutics Precigen Precision BioSciences SOTIO Biotech Synthekine TC BioPharm Tessa Therapeutics Ucello Therapeutics Umoja Biopharma Verismo Therapeutics Vor Biopharma Wugen Xenetic Biosciences For more information about this report visit https://www.researchandmarkets.com/r/kmq25o About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

– PBGENE-DMD is a first-in-class in vivo gene editing approach for the majority of Duchenne Muscular Dystrophy patients impacted by dystrophin mutations in the most common ‘hot spot’ region between exons 45-55 – – Final clinical candidate PBGENE-DMD demonstrates compelling preclinical data for durably improving functional benefit over time – – Precision targeting to submit an Investigational New Drug (IND) and/or Clinical Trial Application (CTA) for PBGENE-DMD in 2025 with clinical data expected in 2026 – DURHAM, NC, USA I May 14, 2025 I Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company utilizing its novel proprietary ARCUS® platform to develop in vivo gene editing therapies for diseases with high unmet need, today announced the strategic prioritization and acceleration of PBGENE-DMD, the Company’s first-in-class in vivo gene editing approach for Duchenne Muscular Dystrophy (DMD) and highlighted a PBGENE-DMD poster presentation at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting being held May 13-17, 2025, in New Orleans, Louisiana. “Nomination and acceleration of PBGENE-DMD as our second wholly owned program is a result of the compelling preclinical evidence we have generated to date,” said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences. “Currently, there are no approved treatments or treatments in development that significantly improve muscle function over time to beneficially alter the long-term prognosis of this devastating disease. PBGENE-DMD is the first in vivo gene editing program that has the potential to transform the treatment paradigm and deliver durable functional improvement for most patients, as up to 60% of those afflicted carry mutations in the ‘hot spot’ region between exons 45-55. Based on these data, the significant unmet need in DMD and the clear regulatory guidance established for new therapeutics in DMD, we are committed to advancing PBGENE-DMD to the next stage of development. We look forward to rapidly advancing this program toward the clinic as our second wholly owned program after PBGENE-HBV and further establishing the therapeutic potential of ARCUS in vivo gene editing.” DMD is a genetic disease caused by mutations in the dystrophin gene that prevent production of the dystrophin protein and affects approximately 15,000 patients in the U.S. alone. There are currently no approved therapies that can drive significant and durable functional muscle improvements. PBGENE-DMD employs two complementary ARCUS nucleases delivered in a single AAV to excise exons 45-55 of the dystrophin gene with the aim of restoring the body’s natural production of a functional dystrophin protein. “PBGENE-DMD has the potential to provide a one-time, durable intervention that could allow for lifelong benefits in muscle regeneration and function. Preclinical models have shown that PBGENE-DMD results in significant and sustained improvement of maximum force output by restoring the human body’s production of a functional, near full-length dystrophin protein,” added Cassie Gorsuch, Ph.D., Chief Scientific Officer at Precision BioSciences. “Approximately one in every 3,500–5,000 males in the United States is afflicted with DMD, and these patients have limited treatment options. Our prioritization of PBGENE-DMD in conjunction with long term, preclinical functional improvement reinforces our belief in the program and its potential to address significant unmet need for patients living with DMD.” In preclinical data being presented at ASGCT, PBGENE-DMD demonstrated significant and durable functional improvement in a humanized DMD mouse model. Following AAV delivery,PBGENE-DMD restored the body’s ability to produce a functional dystrophin protein broadly across multiple muscles, including cardiac and skeletal muscles. Over the course of 9 months, mice treated with PBGENE-DMD showed increased dystrophin protein expression resulting in substantial and sustained functional muscle improvement. In addition, PBGENE-DMD-edited dystrophin mRNA transcript in muscle satellite stem cells, which are progenitor cells for new muscle cells, supports the potential for long-term durability. “Precision’s ARCUS gene excision approach targeting exons 45-55 represents a novel approach to addressing the underlying disease for the majority of patients with Duchenne muscular dystrophy,” said Debra Miller, founder and CEO of CureDuchenne. “We are excited by the potential of this approach and look forward to Precision educating the DMD community about it at our upcoming FUTURES National Conference on May 24.” CureDuchenne is a nonprofit organization recognized as the global leader in research, patient care and innovation for improving and extending the lives of those with Duchenne muscular dystrophy. Precision is working diligently and targeting to file an IND and/or CTA in 2025 with clinical data anticipated in 2026. The Company believes that its current cash runway will be sufficient to progress both PBGENE-HBV, its current Phase 1 clinical program, and PBGENE-DMD through Phase 1 clinical readouts. In order to accelerate development of PBGENE-DMD and maintain operational capability to pursue PBGENE-HBV and PBGENE-DMD through Phase 1 clinical results, Precision plans to pause development of PBGENE-3243, its potential treatment for m.3243-associated mitochondrial disease, and will stage future development alone or with partners following completion of the Phase 1 ELIMINATE-B trial and after the PBGENE-DMD program enters the clinic. Precision has completed pre-IND discussions with regulators for PBGENE-3243 and the final clinical candidate is ready to commence toxicology studies. “We remain excited about the potential for PBGENE-3243 to help people living with m.3243 mitochondrial diseases and remain committed to those afflicted with m.3243 associated mitochondrial disease in the future, alone or through partnerships,” added Mr. Amoroso. Conference Call Information Precision BioSciences will host a conference call on Thursday, May 15 at 8:00 am ET. To access the live conference call, participants may register here . The live audio webcast of the call will be available in the Investors section under Events & Presentations at investor.precisionbiosciences.com. An archived replay of the webcast will be available for approximately 30 days following the event. PBGENE-DMD Presentation Details: Title: ARCUS-Mediated Gene Editing Excision of Exons 45-55 of the Human Dystrophin Gene using PBGENE-DMD Leads to Functional Dystrophin Protein and Durable Restoration of Skeletal Muscle-Function In Vivo for the Treatment of Duchenne Muscular Dystrophy Session: Poster Reception Date and Time: Wednesday, May 14, 2025, 5:30 PM – 7:00 PM CT Location: Poster Hall I2 About Precision BioSciences, Inc. Precision BioSciences, Inc. is a clinical stage gene editing company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform that differs from other technologies in the way it cuts, its smaller size, and its simpler structure. Precision’s two lead programs, PBGENE-HBV, for chronic Hepatitis B, and PBGENE-DMD, for Duchenne Muscular Dystrophy are focused on areas with large patient populations with high unmet need. Using ARCUS, the Company’s pipeline prioritizes in vivo gene editing candidates designed to deliver lasting cures for the broadest range of genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit www.precisionbiosciences.com . SOURCE: Precision Biosciences