Motixafortide

Synergy was demonstrated in a combination arm of GLIX1 and the PARP inhibitor olaparib at low doses, with substantially better efficacy compared to the control arm and compared to each drug individually at its optimal dose GLIX1 in combination with olaparib also showed comparable efficacy to that seen with the chemotherapy drug cisplatin Results reinforce synthetic lethality between GLIX1 and PARP inhibitors, indicating that GLIX1 can broaden the use of PARPi in ovarian cancer TEL AVIV, Israel and OSLO, Norway, July 8, 2026 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, and Hemispherian AS, a clinical-stage oncology company developing novel small molecule therapeutics, today announced highly encouraging new preclinical data demonstrating strong synergy between GLIX1 and PARP inhibitors in a patient-derived xenograft (PDX) model of ovarian cancer. Continue Reading Hemispherian Logo Ovarian cancer remains a major therapeutic challenge, particularly in homologous recombination (HR)-proficient disease where PARP inhibitors (PARPi) presently have limited efficacy, as well as for patients with platinum-resistance. GLIX1 in combination with PARPi is expected to result in synthetic lethality, a mechanism in which GLIX1-induced single-stranded DNA breaks overcome PARP inhibitors' requirement for HR-deficiency, enabling synergistic activity in HR-proficient cancers. This effect was first observed in vitro, where GLIX1 showed reproducible synergy across different PARP inhibitors and multiple HR-proficient ovarian cancer cell lines, with very high ZIP synergy scores. "We are very excited to observe, in a patient-derived ovarian cancer model, the synergistic effect as we anticipated based on the mechanistic rationale and as demonstrated by in vitro data," said Philip Serlin, Chief Executive Officer of BioLineRx. "GLIX1 has the potential to sensitize patients to PARP inhibitors as well as to potentially address the huge unmet need for patients with platinum-resistance. Based on these highly encouraging data, we plan to include an ovarian cancer arm in the expansion part of our ongoing Phase 1/2a study." Today's results represent a compelling in vivo confirmation of GLIX1 and PARPi synergy from an HR-proficient ovarian cancer PDX model. The study included six arms: cisplatin, GLIX1 monotherapy and olaparib monotherapy (all at doses expected to be optimal), low-dose GLIX1, a low-dose GLIX1/olaparib combination arm, and a control arm Results show substantially better efficacy in the combination arm versus the control arm and versus the monotherapy arms, despite using lower doses in the combination arm The low-dose GLIX1/olaparib combination tumor reduction was similar to cisplatin, the current chemotherapy benchmark BioLineRx and Hemispherian plan to present the data from this study at one or more future medical conferences. About Ovarian Cancer Ovarian cancer is the deadliest gynecologic malignancy in the United States, with an estimated approximately 21,000 new cases and 12,450 deaths projected in 2026. Standard first-line treatment consists of cytoreductive surgery and platinum-based chemotherapy, with PARP inhibitors used as maintenance therapy in selected patients, particularly those with BRCA-mutated or homologous recombination (HR)-deficient disease. However, PARP inhibitors are markedly less effective in patients with HR-proficient tumors, which account for approximately 50% of high-grade serous ovarian cancers and are associated with primary platinum resistance and shorter survival. This leaves a substantial and currently underserved patient population in need of new treatment strategies capable of extending the benefits of PARP inhibitors. About GLIX1 GLIX1 is a first-in-class, orally administered, brain penetrating, small molecule activator of the Ten-Eleven Translocation 2 (TET2) pathway that is commonly inhibited in cancer. Activating the novel TET2 pathway by GLIX1 overwhelms the DNA repair capacity of cancer cells, resulting in apoptotic cancer cell death. About the Phase 1/2a Trial with GLIX1 The Phase 1/2a trial is an open-label, multicenter trial. Part 1 of the trial is a dose escalation study where patients receive GLIX1 daily as monotherapy. This part is expected to recruit up to 30 patients with recurrent and progressive GBM and other high-grade gliomas. The primary objective is to establish a maximum tolerated dose (MTD) and/or a recommended dose based on safety, PK/PD and preliminary efficacy. Updates to the Phase 1/2a trial are anticipated during H2 2026, with full results on the dose escalation part expected in 2027. The Phase 2a expansion part of the trial is planned to include additional indications, including newly diagnosed GBM, as well as select cancers, with GLIX1 as monotherapy or in combination with standard of care (including in combination with PARP inhibitors). These cohorts are expected to identify preliminary efficacy, PD assessments and dose optimization data, serving as the basis for a rapid and effective advanced clinical development plan. For more information on the Phase 1/2a trial, please visit NCT07464925. About Hemispherian Hemispherian AS is a clinical-stage pharmaceutical company developing first-in-class small-molecule cancer therapies. Its lead program, GLIX1, is being advanced in partnership with BioLineRx for the treatment of glioblastoma and a broad range of solid tumors. The company is headquartered in Oslo, Norway, and collaborates with leading academic and clinical institutions worldwide. Learn more at or on LinkedIn. About BioLineRx BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX) is a biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases. The Company's lead development asset is GLIX1, a first-in-class, oral, small molecule targeting DNA damage response in glioblastoma and other solid tumors, for which a Phase 1/2a clinical trial has been initiated in the first quarter of 2026. GLIX1 is being developed under a collaboration with Hemispherian AS. The Company's first approved product, APHEXDA® (motixafortide), is indicated in the U.S. for stem cell mobilization for autologous transplantation in multiple myeloma, and is being commercialized by Ayrmid Ltd. (globally, except Asia) and Gloria Biosciences (in Asia). BioLineRx has retained the rights to develop motixafortide in solid tumors, including metastatic pancreatic cancer (PDAC), and has a Phase 2b PDAC trial currently ongoing under a collaboration with Columbia University. Learn more about who we are, what we do, and how we do it at , or on LinkedIn. Forward Looking Statement Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "anticipates," "believes," "could," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," and "would," and describe opinions about future events. These include statements regarding management's expectations, beliefs and intentions regarding, among other things, GLIX1's potential to sensitize patients to PARP inhibitors as well as the potential to address the need for patients with platinum-resistance. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the clinical development, commercialization and market acceptance of GLIX1 and motixafortide including the degree and pace of market uptake of APHEXDA for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients; the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials and other therapeutic candidate development efforts; BioLineRx's ability to advance GLIX1 and motixafortide into clinical trials or to successfully complete its preclinical studies or clinical trials; whether the clinical trial results for GLIX1 and motixafortide will be predictive of real-world results; BioLineRx's receipt of regulatory approvals for GLIX1 and motixafortide and the timing of other regulatory filings and approvals; whether access to GLIX1 and motixafortide is achieved in a commercially viable manner and whether GLIX1 and motixafortide receives adequate reimbursement from third-party payors; BioLineRx's ability to establish, manage, and maintain corporate collaborations, as well as the ability of BioLineRx's collaborators to execute on their development and commercialization plans; BioLineRx's ability to integrate new therapeutic candidates and new personnel, as well as new collaborations; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection that BioLineRx's is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its need for and ability to access sufficient additional financing; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; BioLineRx's ability to maintain the listing of its ADSs on Nasdaq; statements as to the impact of the political and security situation in Israel on BioLineRx's business which may exacerbate the magnitude of the factors discussed above. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 23, 2026. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law. Contacts: For BioLineRx: United States Chuck Padala LifeSci Advisors, LLC [email protected] Israel Moran Meir LifeSci Advisors, LLC [email protected] For Hemispherian AS: Zeno Albisser, CEO [email protected] Logo: Logo: SOURCE BioLineRx Ltd.; Hemispherian AS 21% more press release views with Request a Demo

C-X-C趋化因子受体4（CXCR4）因其在肿瘤进展和转移中通过维持干细胞样表型的关键作用，已成为癌症治疗的重要分子生物标志物。该受体在20余种癌症中过表达，包括实体瘤和血液系统恶性肿瘤，且常与肿瘤侵袭性强和预后不良相关。CXCR4最初被认为是HIV感染的共受体，过去数十年间已发现了大量靶向CXCR4的配体和拮抗剂，涵盖小分子、多肽和生物制剂。尽管目前仅少数应用于癌症治疗领域，但近期以CXCR4为分子靶点的生物技术进展显示出革新未来癌症治疗的巨大潜力。 CXCR4的靶点生物学基础  分子结构与信号转导机制  CXCR4属于G蛋白偶联受体超家族中的趋化因子受体亚类，由352个氨基酸组成，具有典型的七次跨膜螺旋结构。其唯一内源性配体CXCL12，又称基质细胞衍生因子1（SDF-1），是一种由68个氨基酸构成的趋化因子。当CXCL12与CXCR4结合后，受体构象发生改变，进而激活多种下游信号通路，包括磷脂酰肌醇3-激酶（PI3K）通路、磷脂酶C（PLC）通路、Janus激酶/信号转导与转录激活因子（JAK/STAT）通路以及丝裂原活化蛋白激酶（MAPK）通路。 图1. CXCR4在生理及病理过程中的信号转导[1]  生理与病理功能  CXCR4及其配体CXCL12构成的信号轴在机体正常生理过程中不可或缺。在胚胎发育阶段，该信号轴参与心血管系统形成、神经嵴细胞定向迁移及肾脏器官发生。在成体造血系统中，CXCR4是造血干细胞归巢至骨髓微环境的关键分子，维持造血稳态，同时参与B细胞发育成熟及淋巴细胞再循环。在组织损伤修复中，CXCR4介导间充质干细胞向损伤部位募集并促进血管新生。 然而，当CXCR4信号轴调控失衡时，其病理效应同样显著。在血液系统恶性肿瘤中，白血病细胞和多发性骨髓瘤细胞高表达CXCR4，沿CXCL12浓度梯度归巢至骨髓保护性微环境，逃避化疗杀伤，是耐药和复发的重要机制。在实体瘤转移中，肿瘤细胞上调CXCR4使其能够识别远处器官（如骨骼、肺、肝脏和淋巴结）中CXCL12富集区域，实现定向转移。此外，CXCL12梯度可招募调节性T细胞和髓源性抑制细胞至肿瘤微环境，参与免疫抑制。在罕见遗传病WHIM综合征中，CXCR4基因C端功能获得性突变导致受体脱敏障碍，引起白细胞骨髓滞留，临床表现为疣、低丙种球蛋白血症、感染和骨髓粒细胞缺乏。  肿瘤微环境中的核心角色  CXCR4在癌症进展中发挥多重关键作用。其过度表达通过激活MAPK、PI3K/Akt和PLC信号通路促进肿瘤细胞增殖，同时通过JAK/STAT通路诱导药物耐药性和复发，具体机制包括上调抗凋亡信号、下调细胞死亡受体表达，以及协同免疫检查点（CTLA-4、PD-L1等）帮助癌细胞逃避免疫监视。在转移方面，CXCR4+癌干细胞通过激活Rac1和MMP-2/MMP-14增强肿瘤侵袭与迁移能力，并通过促进癌细胞对内皮细胞的黏附及VEGF/VEGFR上调加速血管生成，使癌细胞具备进入循环系统、归巢至CXCL12/SDF-1分泌器官并定植转移的能力。此外，CXCR4+上皮癌细胞通过调控肿瘤微环境促进恶性进展。肿瘤相关间质细胞分泌的高水平CXCL12以旁分泌方式刺激细胞增殖、诱导上皮间充质转化（EMT），并增强肿瘤边缘的迁移与侵袭。同时，CXCL12招募调节性T细胞、肿瘤相关巨噬细胞和髓系来源抑制细胞等免疫抑制性群体浸润肿瘤，形成免疫豁免屏障，阻断抗肿瘤免疫应答。 图2. CXCR4在癌症中的作用[1] CXCR4靶向治疗的临床应用现状  已获批上市药物  全球已获批上市的CXCR4靶向药物目前共有3款：2008年，双环胺类小分子Plerixafor（普乐沙福）获FDA批准，联合G-CSF用于多发性骨髓瘤和非霍奇金淋巴瘤患者的造血干细胞动员，首次验证了CXCR4作为可成药靶点的可行性；2023年9月，环肽类拮抗剂Motixafortide（Aphexda/莫替福肽）获批同适应症，以更长的受体占位时间和更优的动员效率成为该领域十年来首个新药，目前还在探索联合PD-1抑制剂用于胰腺癌等实体瘤治疗；2024年4月，口服小分子Mavorixafor获批用于罕见遗传病WHIM综合征，通过抑制CXCR4的过度激活信号恢复白细胞正常分布，成为该病史上首个靶向治疗药物——三款药物从干细胞动员到罕见病，逐次拓宽了CXCR4靶点的临床边界。  诊断显像探针  在诊断领域，以环肽类分子 Pentixafor 为配体的放射性核素标记探针实现了重要突破。作为首个进入临床研究的 CXCR4 靶向 PET 探针，镓-68 标记的 Pentixafor（[⁶⁸Ga]Pentixafor）具有三大核心优势：对人CXCR4 的低纳摩尔级亲和力、快速的肾脏清除动力学，以及由此带来的低背景信号。目前，该探针已在德国等欧洲国家以医院豁免或临床试验形式开展应用。 在肿瘤诊断中，[⁶⁸Ga]Pentixafor PET 已成功用于多发性骨髓瘤、淋巴瘤等血液肿瘤及胶质母细胞瘤等部分实体瘤的 CXCR4 表达可视化。在心血管领域，该探针可无创评估动脉粥样硬化斑块的 CXCR4 阳性炎症细胞浸润，既能识别易损斑块，又能评价他汀类药物等抗炎干预的疗效。此外，心肌梗死后梗死区 CXCR4 在炎症修复期显著上调，PET成像可据此追踪炎症消退与组织修复的动态过程。在神经炎症方面，[⁶⁸Ga]Pentixafor 已用于多发性硬化等疾病的脑内炎症负荷定量评估。 在治疗端，与诊断探针配对的治疗型配体 [¹⁷⁷Lu]Pentixather 和 [⁹⁰Y]Pentixather 已进入临床研究。二者通过 CXCR4 靶向内照射杀伤高表达病灶，与 [⁶⁸Ga]Pentixafor PET 共同构成诊疗一体化闭环。 临床在研药物盘点 CXCR4在20余种癌症类型中过表达，多种拮抗剂（主要为小分子、多肽和抗体）已被开发用于靶向该受体，其中多项已进入临床试验阶段。 表1. 靶向CXCR4已上市或进入临床研究阶段药物研发管线（数据来源于智慧芽）  小分子拮抗剂  Plerixafor（普乐沙福）是最经典的CXCR4小分子拮抗剂，2008年获FDA批准联合G-CSF动员造血干细胞用于淋巴瘤和骨髓瘤患者自体移植，兼具化疗增敏作用，目前已注册超过150项临床试验。Mavorixafor为口服CXCR4拮抗剂，可增强CD8+ T细胞浸润、减少免疫抑制细胞，联合免疫检查点抑制剂在肾细胞癌和黑色素瘤中安全性良好，近期获FDA批准用于WHIM综合征。Burixafor联合G-CSF及普萘洛尔的三联方案较标准动员方案效果更优，II期试验正在进行。GMI-1359为CXCR4/E-selectin双靶点抑制剂，临床前显示促白血病细胞动员和骨转移抗肿瘤活性，联合多西他赛增敏效果优于单一CXCR4拮抗剂。Burixafor（GPC-100）可动员造血干细胞，联合G-CSF在NHL、霍奇金淋巴瘤和MM中成功实现干细胞动员。其与普萘洛尔及G-CSF的三联方案较标准普乐沙福联合G-CSF方案显示出更优动员效果，相关II期试验正在进行。GMI-1359为CXCR4和E-selectin双靶点抑制剂，临床前在AML和MM模型中促进白血病细胞动员并延长生存，且具有骨转移抗肿瘤活性，联合多西他赛增敏效果优于单靶点CXCR4拮抗剂。目前正在HR⁺转移性乳腺癌患者中评估其靶点结合效应。  多肽  多肽类CXCR4拮抗剂是肿瘤治疗中另一类重要方向。其中进展最快的是Motixafortide（BL-8040），已获FDA批准（商品名Aphexda），联合G-CSF用于多发性骨髓瘤患者的造血干细胞动员和自体移植，III期GENESIS试验安全性良好。目前其联合阿糖胞苷治疗复发/难治AML、联合PD-1抑制剂及化疗用于转移性胰腺癌等多项研究正在推进，并探索用于镰状细胞病的基因治疗干细胞动员。Balixafortide联合艾日布林未能在HER2阴性转移性乳腺癌中增效，但可单独动员造血干细胞。CTCE-9908（PTX-9908）在多种肿瘤模型中抑制生长和转移，目前已进入肝癌I/II期临床，评估其在肝动脉化疗栓塞后预防肝细胞癌复发的作用。  抗体类药物  Ulocuplumab（BMS-936564）是百时美施贵宝开发的全人源IgG4抗CXCR4单克隆抗体。临床前研究显示，其在AML、非霍奇金淋巴瘤和多发性骨髓瘤等血液肿瘤中通过非caspase依赖的活性氧产生途径诱导凋亡，发挥抗肿瘤效应。临床方面，Ulocuplumab联合来那度胺和硼替佐米在复发/难治多发性骨髓瘤患者中表现出高反应率，包括既往重度治疗人群，安全性可接受；联合伊布替尼治疗Waldenström巨球蛋白血症同样安全。然而，其联合阿糖胞苷治疗AML的I/II期试验因入组缓慢及商业目标变更而终止，胰腺癌和小细胞肺癌试验也因疗效不足终止。 LY2624587是礼来开发的全人源化单抗，通过受体内化下调细胞表面CXCR4，临床前模型中促进凋亡，但其造血干细胞动员能力明显弱于同类多肽拮抗剂LY2510924。PF-06747143为辉瑞的人源化IgG1抗体，区别于Ulocuplumab，其具备抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）双重效应机制，临床前在AML和多发性骨髓瘤模型中与化疗显著协同，但I期AML试验因战略优先调整终止。F50067同样依赖ADCC和CDC机制，但因血小板减少等血液学毒性在复发/难治骨髓瘤试验中终止。此外，双表位纳米抗体ALX-0651亦未能在临床试验中优于现有标准治疗。  寡核苷酸类药物  已发现多种调控CXCR4的miRNA具有肿瘤治疗潜力：miR-146、miR-193-5p可抑制结直肠癌增殖并增强化疗敏感性；miR-139可降低乳腺癌干细胞侵袭能力；miR-613能抑制骨肉瘤转移。然而，这些miRNA的临床应用受限于血液降解和脱靶毒性，目前研究正聚焦于开发纳米载体等递送系统以提高稳定性与靶向性。  放射性核素治疗  放射性核素治疗是CXCR4靶向药物最具前景的发展方向之一，其核心在于将高亲和力CXCR4配体与治疗性核素偶联，实现肿瘤精准内照射。钇-90和镥-177标记的Pentixather均已进入临床研究：90Y-Pentixather在多发性骨髓瘤的首次人体试验及CNS淋巴瘤的临床试验中展现出治疗潜力；177Lu-Pentixather因β粒子射程较短（约2 mm）、半衰期更长，对微小病灶更具剂量学优势，正在神经内分泌肿瘤等适应症中开展I/II期评估。两者与诊断探针[⁶⁸Ga]Pentixafor配对，构成显像筛选—精准治疗的诊疗一体化闭环。 在临床前研究中，锕-225等α粒子发射体标记的环肽配体正被积极探索。α粒子具有高传能线密度，短射程内释放巨大能量，对微转移灶和单个肿瘤细胞杀伤力极强，有望弥补常规β粒子治疗对微小病灶效果不佳的短板。 南模生物CXCR4相关小鼠模型 南模生物长期致力于各种小鼠模型的开发，可以提供多种CXCR4靶点相关小鼠，例如人源化CXCR4小鼠，为相关药物的临床前药理药效评估和安全性评价提供强有力的工具。 表2. 南模生物CXCR4靶点相关小鼠品系 hCXCR4(2), 目录号：NM-HU-251443 图3. 通过流式细胞术检测WT C57BL/6小鼠与HO hCXCR4(2)小鼠脾脏中T细胞、B细胞及CD11b+细胞表面的CXCR4表达。hCXCR4仅在HO hCXCR4(2)小鼠中检出，WT小鼠中未检测到。 图4. 通过流式细胞术检测WT C57BL/6小鼠与HO hCXCR4(2)小鼠骨髓中T细胞、B细胞及CD11b+细胞表面的CXCR4表达。hCXCR4仅在HO hCXCR4(2)小鼠中检出，WT小鼠中未检测到。 全人源抗hCXCR4抗体ulocuplumab的体内靶点结合验证 图5. 通过流式细胞术检测WT C57BL/6小鼠与HO hCXCR4(2)小鼠骨髓中T细胞、B细胞及CD11b+细胞表面ulocuplumab的结合。ulocuplumab仅和HO hCXCR4(2)小鼠的细胞结合，不与WT小鼠的细胞结合。 相关阅读 ASCO 2026炸场！94项口头报告+12项LBA，这些模型与服务成研发硬核助攻 从ASCO 2026爆款PD-1/VEGF双抗，看人源化小鼠模型如何支撑临床前研发 细说肝癌治疗潜力靶点--GPC3 做ADC项目，这些模型和服务可能正是你需要的！ 人源化小鼠模型：CAR-T疗法临床前验证的关键工具与转化桥梁 从ex vivo到in vivo：CAR-T细胞治疗的第二次革命 世界癌症日｜“以人为本，携手抗癌”，南模肿瘤平台驱动新药突破 >>> 点击进入药靶百科合集 Reference： [1] Rueda, A., Serna, N., Mangues, R. et al. Targeting the chemokine receptor CXCR4 for cancer therapies. Biomark Res 13, 68 (2025). [2] Yang, B., Hu, W., Zhang, X., Gai, Y., An, R., Qin, C., Li, M., Lan, X. (2026). The CXCR4-targeted theranostics era: a comprehensive review of a decade of progress (2015–2025). Theranostics, 16(12), 6576-6599. 关于我们 上海南方模式生物科技股份有限公司（Shanghai Model Organisms Center, Inc.，简称"南模生物"），成立于2000年9月，是一家上交所科创板上市高科技生物公司（股票代码：688265），始终以编辑基因、解码生命为己任，专注于模式生物领域，打造了以基因修饰动物模型研发为核心，涵盖多物种模型构建、饲养繁育、表型分析、药物临床前评价等多个技术平台，致力于为全球高校、科研院所、制药企业等客户提供全方位、一体化的基因修饰动物模型产品解决方案。 欢迎通过以下方式联系我们： 💬 微信公众号「南模生物SMOC」在线咨询 📞 拨打400-728-0660 📧 发送邮件至marketing@modelorg.com 🔗 点击文末「阅读原文」即可查看更多数据