IL-7

WALTHAM, Mass., April 3, 2024 /PRNewswire/ -- Q32 Bio Inc. (NASDAQ: QTTB) ("Q32 Bio"), a clinical stage biotechnology company focused on developing biologic therapeutics to restore immune homeostasis, today announced the appointment of Lee Kalowski as President and Chief Financial Officer. Mr. Kalowski brings over 20 years of biopharmaceutical experience with a focus on strategy, raising capital, and financial operations. "Lee has been part of the Q32 Bio team over the past five months as our interim Chief Financial Officer and an invaluable member of the team driving the execution and closing of our recent transactions. I am pleased to welcome Lee as a permanent member of the team, as we transition into a publicly traded company," said Jodie Morrison, Chief Executive Officer of Q32 Bio. "Lee is a deeply experienced biopharmaceutical executive with a proven track record of taking companies public, raising capital, and overseeing finance and operations at multiple publicly traded companies." "I am excited to be joining full-time in my new role during this transformative time for the Company," said Mr. Kalowski. "Q32 Bio has the potential to make meaningful strides in the treatment of autoimmune and inflammatory diseases and I look forward to continuing to work with the Q32 Bio leadership team as we advance bempikibart to Phase 2 clinical data in the second half of this year and ADX-097 to Phase 2 clinical data in the second half of 2025." Prior to joining Q32 Bio, Mr. Kalowski served as President and Chief Financial Officer of Bicycle Therapeutics where he led strategic finance and operations and oversaw the company's transition to a public clinical-stage biotech company. While at Bicycle, Mr. Kalowski led the IPO in 2019 and helped raise $1 Billion in total, including over $700 Million in private, public and non-dilutive financings. Prior to Bicycle, Mr. Kalowski was Chief Financial Officer of Tokai Pharmaceuticals where he helped lead the company's IPO in 2014. Earlier, Mr. Kalowski served in global biotechnology equity research as a Senior Analyst at Credit Suisse covering companies in the biopharmaceutical industry. Mr. Kalowski received a B.A. in Biology and Economics from Union College and an MBA from The Wharton School of the University of Pennsylvania. Mr. Kalowski is currently a board member of Aro Biotherapeutics. About Q32 Bio Q32 Bio is a clinical stage biotechnology company developing biologic therapeutics targeting potent regulators of the innate and adaptive immune systems to re-balance immunity in autoimmune and inflammatory diseases. Q32 Bio's lead programs, focused on the IL-7 / TSLP receptor pathways and complement system, address immune dysregulation to help patients take back control of their lives. Q32 Bio's program for adaptive immunity, bempikibart (ADX-914), is a fully human anti-IL-7Rα antibody that re-regulates adaptive immune function for the treatment of autoimmune diseases. It is being evaluated in two Phase 2 trials for the treatment of atopic dermatitis and alopecia areata. The IL-7 and TSLP pathways have been genetically and biologically implicated in driving several T cell-mediated pathological processes in numerous autoimmune diseases. Q32 Bio's program for innate immunity, ADX-097, is based on a novel platform enabling tissue-targeted regulation of the complement system without long-term systemic blockade – a key differentiator versus current complement therapeutics. Q32 Bio has completed a first-in-human, Phase 1 ascending dose clinical study of ADX-097 in healthy volunteers. For more information, visit . Forward-Looking Statements This communication contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including statements regarding expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of Q32 Bio's product candidates, including bempikibart and ADX-097, and anticipated milestones and timing, among others. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "anticipate," "plan," "likely," "believe," "estimate," "project," "intend," and other similar expressions among others. Statements that are not historical facts are forward-looking statements. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the ability to integrate our business with our merger partner successfully and to achieve anticipated synergies; the possibility that other anticipated benefits of the merger will not be realized, including without limitation, anticipated revenues, expenses, earnings and other financial results, and growth and expansion of our operations, and the anticipated tax treatment of the merger; our ability to retain, attract and hire key personnel; potential adverse reactions or changes to relationships with employees, suppliers or other parties resulting from the completion of the merger; potential business uncertainty, including changes to existing business relationships that could affect our financial performance; the need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; the inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties, including for the manufacture of materials for our research programs, preclinical and clinical studies; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; securities class action litigation; the impact of global pandemics and general economic conditions on our business and operations, including the our preclinical studies and clinical trials; the possibility of system failures or security breaches; risks relating to intellectual property; significant costs incurred as a result of operating as a public company; and such other factors as are set forth in Q32 Bio's periodic public filings with the SEC, including but not limited to those described under the heading "Risk Factors" in our Form 8-filed on March 27, 2024. Except as required by applicable law, we undertake no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. Contacts: Investors: Brendan Burns Media: Sarah Sutton Argot Partners 212.600.1902 [email protected] SOURCE Q32 Bio

ROCKVILLE, Md., April 2, 2024 /PRNewswire/ -- NeoImmuneTech, Inc. (KOSDAQ: 950220), announced that Luke Oh, Ph.D. has been appointed as President and Chief Executive Officer (CEO) of NeoImmuneTech, Inc. (NIT or "NeoImmuneTech"), effective from March 29, 2024 (EDT). Having joined the company as President in January 2024, Dr. Oh now succeeds Dr. Se Hwan Yang, Ph.D., as Chief Executive Officer of NeoImmuneTech, Inc. In his new role, Dr. Oh will lead NeoImmuneTech from its Rockville headquarters and overview all the operations in Korea. Dr. Oh is an expert in regulatory policies and drug development, encompassing both biologics and small molecules. He brings over six years of regulatory experience at the U.S. FDA. His recent tenure at Samsung Bioepis as Vice-President in charge of Regulatory Development was marked by a number of successful preparation and submission of biosimilar applications to regulatory agencies in the US, EU, UK, and Canada. Prior to this position, he has worked as Senior Staff Fellow at the U.S. FDA Division of Clinical Pharmacology III and Division of Inflammation and Immune Pharmacology, and he has held various roles in research and development for leading organizations such as Mallinckrodt Pharmaceuticals, Human Genome Sciences, and Vertex Pharmaceuticals. Dr. Oh has a Ph.D. in Neuroimmunology from the McGill University (Montreal, Canada). Dr. Luke Oh, Ph.D. President and Chief Executive Officer of NeoImmuneTech, Inc. said: "It is an honor to lead NeoImmuneTech into the future, particularly as our main asset, NT-I7, a unique long-acting human IL-7, moves closer to potentially being the first approved treatment for Acute Radiation Syndrome (ARS). I am committed to advancing the work that Dr. Se Hwan Yang initiated, aligning the company on our business priorities, and stepping up this new phase of NeoImmuneTech." About NT-I7 (efineptakin alfa) (rhIL-7-hyFc) NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7 and is being developed in oncologic and immunologic indications, where T cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety pro making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications. About NeoImmuneTech, Inc. NeoImmuneTech, Inc. (NIT) is a clinical-stage T cell-focused biopharmaceutical company dedicated to expanding the horizon of immuno-oncology and enhancing immunity to infectious diseases. NIT is led by the scientific founder and inventor of NT-I7 (efineptakin alfa) and has a strong executive team with rich industry experience. NIT is expanding rapidly in personnel and operations, as well as partnering with industry and academic leaders to investigate NT-I7 as monotherapy and in combination with various immunotherapeutics. For more information, please visit . Forward-looking Statements The statements contained herein may contain certain forward-looking statements relating to NeoImmuneTech, Inc. (the "Company") that are based on its beliefs and expectations about the future. These forward-looking statements are based on a number of assumptions about the future, some of which are beyond the Company's control and are not a guarantee of future performance or developments. Such forward-looking statements are subject to certain risks and uncertainties that could cause actual results to differ materially from those contemplated by the relevant forward-looking statements. The Company does not undertake any obligation to update any forward-looking statements to reflect events that occur or circumstances that arise after the date of these documents. Accordingly, you should not place reliance on any forward-looking information or statements contained herein. Some of the data contained in these documents were obtained from various external sources, and the Company has not independently verified such data. Accordingly, the Company makes no representations as to the accuracy or completeness of the data, and such data involves risks and uncertainties and is subject to change based on various factors. Photo - View original content to download multimedia: SOURCE The NeoImmuneTech, Inc

外源性细胞因子工程化被认为是增强抗肿瘤T细胞免疫的解决方案之一。常见细胞因子对CAR-T细胞的作用包括：细胞因子对CAR-T细胞特性的影响IL-2增强增殖和效应能力IL-7延长潜在寿命，提高效应功能的持久性IL-9维持T细胞干性，增强效应功能IL-15延长细胞寿命IL-8增强T细胞向肿瘤迁移的能力IL-10通过代谢重编程恢复耗竭T细胞功能IL-12直接上调细胞毒性，调节免疫抑制TMEIL-18增强效应功能，重塑TMEIL-23提高效应功能，减少耗竭表型IL-33调节TMEIL-36γ增强细胞毒性，调节TMEIL-37恢复耗竭T细胞功能在实际开发应用中，把握共表达细胞因子的安全性和有效性依然是一个挑战。近期还是有一些相关研究团队继续关注着细胞因子CAR结构的开发。IL-4IL-4是肿瘤细胞在TME中释放的细胞因子，可以通过与T细胞表面的IL-4受体结合来对抗T细胞效应功能。通过转化细胞因子受体CAR(ICR)是抑制这种免疫抑制作用的常见方法，IL-7和IL-21通常是对应转化细胞因子的选择。华师大的研究团队近期则设计了一款4/15NKG2D-CAR，由基于NKG2D的嵌合抗原受体组成，IL-4R作为细胞外结构域共表达，IL-15R作为跨膜和细胞内结构域共表达，从而将IL-4R抑制信号转化为下游的IL-15R激活信号。(doi:10.1016/j.biopha.2023.115740.)4/15NKG2D-CAR-T在小鼠模型中表现出提高细胞毒性、增殖水平、存活率、未分化表型比例等抗肿瘤作用。IL-7(doi:10.1007/s10565-023-09821-w)研究人员设计了一款GPC3-7-19-CAR-T细胞用于治疗HCCs。杀伤效率是单纯GPC3-CAR-T细胞的1.5-2倍。在小鼠实验中表现出提高浸润CD4+ T细胞亚群比例、募集更成熟的DCs、减少PMN-MDSC和Treg细胞浸润，从而诱导TME重塑。该CAR-T在1例GPC3+ 晚期HCC患者身上展开了临床试验。结果显示，CAR-T治疗后，淋巴结节明显缩小，CT扫描显示CAR-T注射后56天患者纵隔淋巴囊萎缩，CD8+ T细胞的比例(67.9%)远高于基线(16.6%)。采用的患者来源CAR-T细胞阳性率为69%。IL-10IL-10在肿瘤发展和发病机制中的作用似乎是自相矛盾的。IL-10本身具有强大的抗肿瘤作用，通过免疫依赖性机制抑制转移，包括抑制浸润性巨噬细胞和血管生成因子以及激活CD8 + T细胞CTL。但同时，研究也报道了TAM产生的IL-10可以通过抑制APC的功能并随后阻断T细胞效应功能，来减弱抗肿瘤反应。矛盾的IL-10(doi:10.1038/s41587-023-02060-8)2024年1月浙江大学/唐力教授团队合作研究开发了一款表达IL-10的CAR-T，在小鼠实验中表现出能够维持线粒体健康、促进OXPHOS代谢等代谢重编程功能，实现肿瘤的消除。据称该CAR-T已经展开IIT临床试验，至少已有11名复发难治性淋巴瘤或复发难治性急性白血病患者达到完全缓解，CR接近100%。重新认识IL-10：提升CAR-T的CR至100%IL-13Rα2IL-13Rα2则和其他细胞因子的使用不同，其主要是因为在肿瘤上特异性表达而被当做靶点。1.(doi:10.1038/s41591-024-02893-z)近期野马生物/希望之城公布了其IL13Rα2靶向CAR-T MB-101的1期临床数据。所有患者的中位总生存期（中位OS）为8个月，高于复发胶质母细胞瘤的6个月预期生存期，而五项细分亚组中，最大剂量第五组OS达10.2个月。(只剩6个月时，他敲响了CAR-T的门)2.(doi:10.1038/s41591-024-02893-z)同期，吉利德/宾法大学也公布了其靶向EGFR和IL13Rα2的鞘内二价CAR T细胞同样治疗复发性胶质母细胞瘤的1期试验中期结果。该CAR-T会在过表达(EGFR扩增)和/或EGFR胞外结构域突变而发生EGFR 激活失调时激活。接受治疗的6名患者的中位随访时间为2.5个月，所有 6 名患者都观察到增强肿瘤大小的减小，部分肿瘤消退维持在第 +28 天及以后。然而，没有一个达到RANO标准的客观反应标准。IL-15(doi:10.3389/fimmu.2023.1165404)2023年信达生物与苏州大学合作设计的一款H9 CAR-IL15 T细胞，旨在解决其Claudin18.2 CAR-T疗法的长期持久性问题。小鼠 IL-15 修饰赋予肿瘤脉管系统靶向 CAR-T 细胞增强的效应器功能、植入和重编程TME能力，从而在免疫功能正常的小鼠中更好地控制肿瘤。其结果显示，在体外实验中，mIL-15对CAR-T细胞杀伤活性的明显影响仅保持较短时间，在超过三轮刺激后消失，可能和IL-15浓度不足相关。尽管IL-15在体外试验中对CAR-T细胞的总体影响通常不显著，但其在体内的作用是显著的。即使没有淋巴细胞清除预处理，H9 CAR-IL15 T细胞仍然产生明显的肿瘤抑制作用，而未修饰的CAR-T细胞几乎没有效果，从而有机会降低淋巴细胞清除方案造成的毒性作用。IL-24(doi:10.1038/s41416-024-02601-1)IL-24主要是通过靶向肿瘤细胞的干性来影响免疫细胞的疗效，可以通过多种途径特异性诱导肿瘤细胞凋亡，包括DNA损伤、SARI诱导、AIF、ATM和beclin-1轴。同时IL-24还可促进T细胞活化、中枢记忆分化和增殖，但不影响其凋亡。郑州大学研究人员通过构建IL-24 CAR-T细胞，旨在通过IL-24影响抗原丢失的肿瘤细胞对CAR-T的耐药性。体内模型显示，分泌IL-24的CAR-T细胞能更好地控制晚期肿瘤和复发。小结目前很多细胞因子CAR-T都能在安全性方面有较好表现，但实际有效性还是参差不齐的。其他参考文献：Shi H,et al.(2023) IL-15 armoring enhances the antitumor efficacy of claudin 18.2-targeting CAR-T cells in syngeneic mouse tumor models. Front. Immunol. 14:1165404. doi: 10.3389/fimmu.2023.1165404