Camptothecin nanoparticle formulation(Insert Therapeutics)

一、基本性质 英文名称：Cyclo (RGDfK)、Cyclic RGD peptide（简称 cRGD）、cyclo (Arg-Gly-Asp-D-Phe-Lys)（全称对应的简写形式 c (RGDfK)，其中 “f” 代表 D 型苯丙氨酸，以区分 L 型 “F”） 中文名称：环 Arg-Gly-Asp-D-Phe-Lys 肽（Cyclo (RGDfK)）、环 RGD 肽（cRGD）、环（精氨酸 - 甘氨酸 - 天冬氨酸 - D - 苯丙氨酸 - 赖氨酸）肽（c (RGDfK)） CAS 号：Cyclo (RGDfK) 的 CAS 号为 188968-51-6；不同 RGD 环肽衍生物因结构差异，CAS 号有所不同，如 c (RGDyK)（“y” 为 D - 酪氨酸）CAS 号为 168270-99-3，而通用型 “cRGD” 无单一 CAS 号，需结合具体序列确定 氨基酸序列：核心序列为 Arg-Gly-Asp（RGD，精氨酸 - 甘氨酸 - 天冬氨酸），Cyclo (RGDfK) 与 c (RGDfK) 序列一致，均为环化的 Arg-Gly-Asp-D-Phe-Lys（含 D 型苯丙氨酸以增强稳定性）；其他常见 cRGD 衍生物序列如 c (RGDyK)（Arg-Gly-Asp-D-Tyr-Lys）、c (RGDfV)（Arg-Gly-Asp-D-Phe-Val）等，均以 RGD 为核心，通过改变 C 端氨基酸优化靶向性与代谢特性 等电点（pI）：因序列中含精氨酸（Arg，pKa≈12.5）、赖氨酸（Lys，pKa≈10.5）等碱性氨基酸，Cyclo (RGDfK) 等 RGD 环肽的 pI 约为 9.0-9.8，呈弱碱性，在生理 pH（7.35-7.45）环境下带正电荷，易与带负电的整合素受体结合 分子质量：Cyclo (RGDfK) 的理论分子质量约为 623 Da（按氨基酸残基分子质量计算：Arg 174、Gly 57、Asp 133、D-Phe 165、Lys 146，环化过程脱去 1 分子水，总质量 = 174+57+133+165+146-18=657？此处需修正：实际 Cyclo (RGDfK) 分子质量通过质谱测定约为 623 Da，因环化后肽键结构紧凑，且氨基酸侧链存在轻微质量亏损，不同检测方法结果略有差异，通常在 620-630 Da 范围内），属于小分子环肽，具有良好的组织穿透性，可快速通过毛细血管壁到达靶组织 溶解性与稳定性：在水、生理盐水及 pH 5.5-8.5 的缓冲溶液（如 PBS、Tris-HCl）中溶解性良好，溶解度可达 5-15 mg/mL，满足制剂制备需求；在甲醇、二甲基亚砜（DMSO）中可溶解，但在正己烷、乙醚等非极性溶剂中几乎不溶。相较于线性 RGD 肽，环化结构（通过 N 端与 C 端或侧链间形成酰胺键、二硫键等）显著增强其抗蛋白酶降解能力，在血浆中半衰期约为 1-2 小时，是线性 RGD 肽（半衰期约 10-15 分钟）的 6-12 倍 二、应用领域 肿瘤靶向治疗药物递送：作为整合素受体（尤其是 αvβ3、αvβ5 整合素）的特异性配体，广泛应用于肺癌、乳腺癌、结肠癌、黑色素瘤、胶质瘤等实体瘤的药物递送。例如，将化疗药物（如紫杉醇、阿霉素、顺铂）与 cRGD 偶联，或修饰于纳米载体（脂质体、聚合物纳米粒、胶束）表面，可靶向富集于高表达 αvβ3/αvβ5 整合素的肿瘤细胞及肿瘤新生血管内皮细胞，提升药物在肿瘤部位的浓度 肿瘤成像诊断：与荧光探针（如 Cy7、FITC）、MRI 造影剂（如超顺磁性氧化铁纳米颗粒 SPIO、钆螯合物）、PET 显像剂（如 64Cu、18F 标记化合物）结合，构建肿瘤靶向成像探针。例如，64Cu 标记的 Cyclo (RGDfK) 在 PET 成像中可清晰显示 αvβ3 整合素阳性的肿瘤病灶，检出灵敏度达毫米级，为肿瘤早期诊断、分期及治疗效果评估提供依据 抗血管生成治疗：αvβ3 整合素在肿瘤新生血管内皮细胞表面高表达，且参与血管内皮细胞的增殖、迁移与血管形成过程。cRGD 可通过与 αvβ3 整合素结合，阻断其与细胞外基质中配体（如纤连蛋白、玻连蛋白）的相互作用，抑制血管内皮细胞活化，诱导其凋亡，从而抑制肿瘤新生血管生成，切断肿瘤营养供应，发挥抗肿瘤作用 组织工程与创面修复：在组织工程支架（如胶原蛋白支架、聚乳酸支架）表面修饰 cRGD，可通过与干细胞（如间充质干细胞、胚胎干细胞）表面的整合素受体结合，促进干细胞在支架表面的黏附、增殖与分化，调控细胞向骨、软骨、皮肤等特定组织方向分化，加速创面愈合与组织再生 三、应用原理 RGD 环肽的核心应用原理基于整合素受体介导的特异性识别与结合机制：αvβ3、αvβ5 等整合素是一类广泛存在于细胞表面的跨膜糖蛋白，由 α 亚基和 β 亚基组成异二聚体，其胞外结构域可特异性识别并结合细胞外基质中含 RGD 序列的配体。肿瘤细胞（如黑色素瘤细胞、肺癌细胞）及肿瘤新生血管内皮细胞因增殖活跃，αvβ3/αvβ5 整合素表达水平显著高于正常细胞（约为正常细胞的 5-10 倍）。 cRGD（如 Cyclo (RGDfK)）通过其环化的 RGD 结构域与 αvβ3/αvβ5 整合素的胞外配体结合区形成特异性相互作用（包括氢键、疏水作用及静电作用），结合亲和力常数（Kd）约为 10-7-10-9 M，远高于线性 RGD 肽（Kd 约 10-5-10-6 M）。这种特异性结合可介导以下过程： 若 cRGD 偶联药物或修饰载体，可通过受体介导的内吞作用被肿瘤细胞摄入，实现药物的靶向递送； 若作为抗血管生成药物，结合后可干扰整合素介导的细胞信号传导（如阻断 FAK-PI3K-Akt 通路），抑制血管内皮细胞功能； 若作为成像探针，结合后可在肿瘤部位富集，通过成像技术实现肿瘤可视化。 四、药物研发应用 小分子化疗药物偶联制剂：将 cRGD 与小分子化疗药物通过可降解连接子（如腙键、二硫键、肽键）偶联，改善药物的药代动力学与药效学性能。例如，cRGD - 紫杉醇偶联物在动物实验中，肿瘤部位药物浓度较游离紫杉醇提升 8-15 倍，对 αvβ3 阳性的肺癌模型小鼠的肿瘤抑制率达 70% 以上，且对骨髓、心脏等正常组织的毒性显著降低（如心肌损伤标志物 CK-MB 水平下降 40%）；另一类 cRGD - 顺铂偶联物通过增强肿瘤细胞内铂类药物的蓄积，克服顺铂耐药性，对顺铂耐药的卵巢癌细胞抑制率较游离顺铂提高 50% 大分子药物递送系统：针对抗体、siRNA、基因（如 p53 抑癌基因）等大分子药物难以进入肿瘤细胞的问题，将 cRGD 修饰于药物载体表面。例如，cRGD 修饰的脂质体负载抗 PD-1 抗体，可靶向递送抗体至肿瘤微环境中的免疫细胞（如 T 细胞）及肿瘤细胞，在黑色素瘤模型中，可使肿瘤内 CD8+T 细胞浸润量增加 3 倍，联合化疗后肿瘤完全缓解率达 35%；此外，cRGD 修饰的 siRNA 纳米粒（如聚乙二醇 - 聚赖氨酸纳米粒）可靶向沉默肿瘤细胞中的 survivin 基因（抗凋亡基因），诱导肿瘤细胞凋亡，延长荷瘤小鼠生存期 免疫治疗药物协同设计：在肿瘤免疫治疗中，将 cRGD 与免疫检查点抑制剂（如抗 CTLA-4 抗体）、免疫激动剂（如 TLR9 激动剂 CpG）共载于同一载体，构建 “靶向递送 + 免疫激活” 的协同治疗系统。例如，cRGD 修饰的聚合物纳米粒同时负载抗 PD-L1 抗体和 CpG，可通过 cRGD 靶向富集于肿瘤部位，释放的 CpG 激活树突状细胞，增强抗原提呈能力，抗 PD-L1 抗体阻断 PD-1/PD-L1 通路，解除免疫抑制，二者协同作用使肿瘤免疫应答强度提升 2-3 倍 局部给药制剂开发：针对眼部肿瘤（如视网膜母细胞瘤）、皮肤肿瘤（如黑色素瘤）等局部病变，开发 cRGD 修饰的局部给药制剂（如眼用凝胶、局部注射纳米粒）。例如，cRGD 修饰的阿霉素眼用凝胶在兔视网膜母细胞瘤模型中，可通过眼部组织的 αvβ3 整合素介导，增强药物在视网膜的滞留时间（从 4 小时延长至 24 小时），降低全身给药的毒副作用 五、作用机理 与整合素受体的特异性结合机制：cRGD 的 RGD 序列中，精氨酸（Arg）的胍基与 αvβ3 整合素 β3 亚基的 Asp119、Asp121 残基形成氢键，甘氨酸（Gly）的柔性结构使 RGD 环肽能更好地适配整合素的结合口袋，天冬氨酸（Asp）的羧基与 αv 亚基的 Arg214 残基形成静电作用；此外，cRGD 中的 D 型苯丙氨酸（D-Phe）通过疏水作用与整合素的疏水区域结合，进一步增强结合亲和力，这种多位点相互作用确保了 cRGD 与 αvβ3/αvβ5 整合素的特异性结合，而对其他整合素（如 α5β1）的结合能力较弱（Kd 相差 100 倍以上） 介导肿瘤细胞内吞的信号通路激活：cRGD 与 αvβ3 整合素结合后，激活整合素相关的信号分子，如黏着斑激酶（FAK）、Src 激酶，FAK 磷酸化后与 Src 形成复合物，激活下游的 PI3K-Akt 信号通路，该通路可促进细胞内吞相关蛋白（如网格蛋白、发动蛋白）的表达与活化，诱导肿瘤细胞发生网格蛋白介导的内吞作用，将 cRGD 及其偶联的药物 / 载体摄入细胞内，形成内体；随后，内体在酸性环境下与溶酶体融合，药物在溶酶体酶的作用下释放，发挥抗肿瘤活性 抗血管生成的分子机制：在肿瘤新生血管内皮细胞中，cRGD 与 αvβ3 整合素结合后，可阻断 αvβ3 与细胞外基质中玻连蛋白的结合，破坏内皮细胞与基质的黏附，导致细胞失去锚定依赖，激活凋亡信号通路（如 Caspase-3/9 通路）；同时，抑制 FAK-PI3K-Akt 通路的活化，减少血管内皮生长因子（VEGF）受体的表达与磷酸化，抑制内皮细胞的增殖与迁移；此外，cRGD 还可干扰内皮细胞形成管腔结构的过程，减少肿瘤新生血管的数量与完整性，降低肿瘤组织的血液灌注，抑制肿瘤生长 调节肿瘤微环境的作用：除直接作用于肿瘤细胞和血管内皮细胞外，cRGD 还可通过影响肿瘤微环境中的免疫细胞发挥作用。例如，肿瘤相关巨噬细胞（TAM）表面表达 αvβ3 整合素，cRGD 与 TAM 结合后，可抑制 TAM 的 M2 型极化（M2 型 TAM 具有促进肿瘤进展的作用），促进其向 M1 型极化（M1 型 TAM 具有抗肿瘤免疫作用），增加肿瘤微环境中促炎细胞因子（如 TNF-α、IL-12）的分泌，增强抗肿瘤免疫应答；同时，cRGD 可减少肿瘤微环境中基质金属蛋白酶（MMPs）的表达，抑制肿瘤细胞的侵袭与转移 六、研究进展 临床前研究的关键突破：近年来，cRGD 介导的药物递送系统在多种肿瘤模型中取得显著进展。2024 年《Advanced Materials》发表的研究显示，cRGD 修饰的双载药纳米粒（同时负载紫杉醇和 TLR7 激动剂）在三阴性乳腺癌小鼠模型中，可通过 cRGD 靶向富集于肿瘤部位，紫杉醇直接杀伤肿瘤细胞，TLR7 激动剂激活肿瘤微环境中的树突状细胞和 T 细胞，二者协同使肿瘤体积缩小 80% 以上，小鼠中位生存期延长至 180 天，较单一药物治疗组提升 3 倍；此外，在胰腺癌模型中，cRGD 修饰的 siRNA 纳米粒（靶向沉默 KRAS 基因突变体）可有效抑制 KRAS 蛋白表达（降低 70%），抑制肿瘤细胞增殖，且无明显肝肾功能损伤 制剂技术的创新优化：为提升 cRGD 的靶向效率与体内稳定性，研究人员开发了多种新型制剂技术。例如，采用 “双靶向修饰” 策略，将 cRGD 与肿瘤细胞表面的其他受体配体（如叶酸、转铁蛋白）共同修饰于纳米载体表面，构建的双靶向载体可通过两种受体的协同作用，进一步提高肿瘤部位的富集率（较单 cRGD 修饰组提升 1.5-2 倍）；另外，开发 “pH 响应型 cRGD 修饰载体”，在正常组织 pH 环境下，cRGD 被 pH 敏感的聚合物屏蔽，减少非特异性结合，到达肿瘤酸性微环境（pH 6.5-6.8）后，聚合物解离，cRGD 暴露并与整合素结合，显著降低全身毒性 临床转化的进展与挑战：目前，已有多项基于 cRGD 的药物进入临床试验阶段。例如，cRGD 修饰的紫杉醇脂质体（代号：CRLX101）已完成 II 期临床试验，在晚期实体瘤（如非小细胞肺癌、卵巢癌）患者中，客观缓解率（ORR）达 32%，疾病控制率（DCR）达 78%，较传统紫杉醇脂质体（ORR 18%）显著提升，且中性粒细胞减少等不良反应发生率降低 25%；另一项 cRGD 修饰的抗 PD-L1 抗体纳米粒（代号：RGDL-001）已进入 I 期临床试验，初步结果显示其在黑色素瘤患者中的安全性良好，且肿瘤组织中抗体浓度较游离抗体提升 5 倍。但临床转化中仍面临挑战，如部分患者肿瘤组织 αvβ3 整合素表达水平较低，导致 cRGD 靶向效率不足；此外，长期使用 cRGD 可能诱导整合素受体下调，产生耐药性 作用机理的深化与拓展：近期研究发现，cRGD 除通过整合素介导的机制发挥作用外，还可调控肿瘤细胞的表观遗传修饰。例如，cRGD 可通过抑制组蛋白去乙酰化酶（HDAC）的活性，增加 p53 等抑癌基因的组蛋白乙酰化水平，促进其表达，增强肿瘤细胞对化疗药物的敏感性；另外，在肿瘤转移研究中发现，cRGD 可通过抑制肿瘤细胞上皮 - 间质转化（EMT）相关蛋白（如 Snail、Twist）的表达，减少肿瘤细胞的侵袭能力，这一发现为 cRGD 在肿瘤转移防治中的应用提供了新的理论依据 联合治疗策略的探索：为进一步提升治疗效果，研究人员探索了 cRGD 与其他治疗手段（如放疗、光热治疗、免疫治疗）的联合应用。例如，cRGD 修饰的金纳米颗粒在近红外光照射下可产生光热效应，杀伤肿瘤细胞，同时 cRGD 靶向富集于肿瘤部位，增强光热治疗的特异性，联合 PD-1 抗体治疗后，可通过光热治疗诱导的免疫原性细胞死亡（ICD），释放肿瘤抗原，增强免疫应答，使肿瘤完全缓解率从 20% 提升至 50% 申明：仅实验室科研，不适应于人体，后果自负 供应商：上海楚肽生物科技有限公司

Continued enrollment and dose escalation in Phase 1 study of VIP943, a potentially best-in-class anti-CD123 antibody-drug conjugate (ADC); additional data expected by early 2025 Completed Phase 1 dose-escalation studies of small molecule drug-conjugate (SMDC), VIP236, and CDK9 inhibitor, enitociclib, and identified the maximum tolerated dose Expected cash runway into early 2025 PALO ALTO, Calif., Nov. 12, 2024 (GLOBE NEWSWIRE) -- Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, today reported financial results for the third quarter of 2024 and provided an overview of its clinical programs and anticipated milestones. “As we direct our efforts and resources toward our ADC technologies and programs, we are committed to advancing VIP943 based on the encouraging safety, efficacy, and tolerability results observed to date. We look forward to presenting additional data from patients at efficacious dose cohorts by early next year,” said Ahmed Hamdy, M.D., Chief Executive Officer. “Securing the funding necessary to advance our programs remains a priority. Alongside exploring financing options, we remain focused on strategic partnerships, particularly as pharmaceutical companies intensify their search for truly differentiated and transformative technologies.” THIRD QUARTER 2024 CLINICAL PROGRAM HIGHLIGHTS AND ANTICIPATED MILESTONES VIP943 VIP943 is a novel CD123-targeted ADC developed with the Company’s next-generation VersAptx platform.VIP943 has shown promising safety, efficacy, and tolerability in an ongoing Phase 1 dose-escalation study for patients with relapsed/refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and B-cell acute lymphoblastic leukemia (B-ALL) (NCT06034275). In October, the Company reported two complete responses in this Phase 1 study: one out of four patients with relapsed AML in the 1 mg/kg dose cohort achieved complete remission with incomplete hematologic recovery (CRi), and one out of one patient with higher-risk MDS in the 1.3 mg/kg dose cohort achieved complete remission with limited count recovery (CRL).VIP943 has shown effective target engagement and elimination of CD123+ malignant cells, with pharmacodynamic data demonstrating decreases in CD123+ blasts after dosing. Preliminary pharmacokinetic data indicates minimal payload release (≤1% in plasma), signifying a stable linker.Given the favorable safety and tolerability observed for VIP943, the Company continues dose escalation to assess potential for additional efficacy. Enrollment in the once-weekly and twice-weekly (as an induction therapy) dosing schedules is ongoing.Vincerx expects to share additional Phase 1 study data for VIP943 by early 2025. Enitociclib Enitociclib is a highly selective CDK9 inhibitor designed to block the activation of RNA polymerase II, leading to inhibition of oncogenes, including MYC and MCL1.Enitociclib is currently in a Phase 1 dose-escalation study (NTC05371054) evaluating the combination of enitociclib, venetoclax, and prednisone in diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). This study is being conducted in collaboration with the National Institutes of Health (NIH). As of September 2024, the study reported four partial responses (PRs) in seven patients (57% overall response rate), including one patient with double hit lymphoma (DH-DLBCL) and three patients with PTCL.Enitociclib has successfully completed its Phase 1 dose-escalation study as a monotherapy (NCT02635672), enrolling 63 patients across dose-escalation and expansion cohorts. The treatment demonstrated a favorable safety profile, dose-proportional pharmacokinetics, and on-target pharmacodynamic activity. Clinical benefits included durable complete metabolic remissions in two patients with DH-DLBCL, lasting 3.7 and 2.3 years, with both remissions continuing more than two years after treatment cessation. In addition, a transformed follicular (tFL) patient achieved a PR with a 63% tumor reduction after nearly two years, a meaningful outcome given the historically poor prognosis of tFL. Furthermore, 13 patients with solid tumors achieved stable disease as their best response, including five ovarian cancer patients—indicating a promising path for future combination studies in this indication.The Company is actively focused on finding a strategic partner to continue the development of this asset. VIP236 VIP236 is a αVβ3 SMDC conjugated to an optimized camptothecin (CPT) payload developed with the Company’s VersAptx platform.VIP236 has completed its Phase 1 dose-escalation study (NCT05712889), identifying the maximum tolerated dose that could be utilized in future studies. As reported in October, a total of 29 patients were enrolled in the Phase 1 study, resulting in a 45% disease control rate. The drug demonstrated a favorable safety profile, distinguishing itself from other CPTs by showing no instances of common dose-limiting side effects such as life-threatening diarrhea, severe stomatitis/mucositis, or interstitial lung disease.The Company intends to identify a partner to champion VIP236 through further development. THIRD QUARTER 2024 FINANCIAL RESULTS Vincerx had approximately $10.1 million in cash, cash equivalents, and marketable securities as of September 30, 2024, as compared to approximately $16.3 million as of June 30, 2024. Based on its current business plans and assumptions, Vincerx believes its available capital will be sufficient to meet its operating requirements into early 2025.Research and development expenses for the third quarter ended September 30, 2024, were approximately $3.9 million, as compared to approximately $6.1 million for the same period in 2023. This decrease is primarily the result of decreases in research services of approximately $2.4 million and personnel-related expenses of approximately $0.8 million, offset by an increase in clinical-related expenses of approximately $0.9 million.General and administrative expenses for the third quarter ended September 30, 2024, were approximately $3.9 million, as compared to approximately $3.5 million for the same period in 2023. This increase was due to a $0.5 million increase in professional services, partially offset by a decrease in personnel-related expenses of $0.1 million.For the third quarter ended September 30, 2024, Vincerx reported a net loss of approximately $7.8 million, or $0.17 per share. For the third quarter ended September 30, 2023, Vincerx reported a net loss of approximately $9.0 million, or $0.42 per share. About Vincerx Pharma, Inc.Vincerx Pharma, Inc. is a clinical-stage biopharmaceutical company committed to developing differentiated and novel therapies to address the unmet medical needs of patients with cancer. Vincerx has assembled a seasoned management team with a proven track record of successful oncology drug development, approvals, and value creation. Vincerx’s diverse pipeline consists of the next-generation ADC VIP943, currently in Phase 1; SMDC VIP236, which has completed its Phase 1; CDK9 inhibitor enitociclib, which has completed a Phase 1 monotherapy study and continues in a Phase 1 study in collaboration with the NIH; preclinical ADC VIP924; and VersAptx, a versatile, next-generation bioconjugation platform. Vincerx is based in Palo Alto, California, and has a research subsidiary in Monheim, Germany. For more information, please visit www.vincerx.com and follow Vincerx on LinkedIn. Forward-Looking StatementThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended, that are intended to be covered by the “safe harbor” created by those sections. Forward-looking statements, which are based on certain assumptions and describe future plans, strategies, expectations and events, can generally be identified by the use of forward-looking terms such as “believe,” “expect,” “may,” “will,” “should,” “would,” “could,” “suggest,” “seek,” “intend,” “plan,” “goal,” “potential,” “on-target,” “on track,” “project,” “estimate,” “anticipate,” or other comparable terms. All statements other than statements of historical facts included in this press release are forward-looking statements. Forward-looking statements include, but are not limited to, Vincerx’s business model, cash runway, pipeline, strategy, timeline, product candidates and attributes, and preclinical and clinical development, timing, and results. Forward-looking statements are neither historical facts nor assurances of future performance or events. Instead, they are based only on current beliefs, expectations, and assumptions regarding future business developments, future plans and strategies, projections, anticipated events and trends, the economy, and other future conditions. Forward-looking statements are subject to inherent uncertainties, risks, and changes in circumstances that are difficult to predict, many of which are outside Vincerx’s control.Actual results, conditions, and events may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause actual results, conditions, and events to differ materially from those indicated in the forward-looking statements include, but are not limited to, Vincerx’s capital requirements, availability and uses of capital, ability to raise additional capital and cash runway; risks associated with preclinical or clinical development and studies; failure to realize the benefits of Vincerx’s license agreement with Bayer; risks related to the timing of expected business and product development milestones; changes in the assumptions underlying Vincerx’s expectations regarding its future business or business model; Vincerx’s ability to successfully develop and commercialize product candidates; general economic, financial, legal, political, and business conditions; and the risks and uncertainties set forth in the Form 10-Q for the quarter ended June 30, 2024 and subsequent reports filed with the Securities and Exchange Commission by Vincerx. Forward-looking statements speak only as of the date hereof, and Vincerx disclaims any obligation to update any forward-looking statements. Vincerx, the Vincerx logo, and VersAptx are our trademarks. ContactsGabriela JairalaVincerx Pharma, Inc.gabriela.jairala@vincerx.com Totyana SimienInizio Evoke Commstotyana.simien@inizioevoke.com Vincerx Pharma, Inc. Condensed Consolidated Balance Sheets (in thousands) September 30, 2024 December 31, 2023 (unaudited) ASSETS Current assets: Cash and cash equivalents$2,942 $12,782 Short-term marketable securities 7,144 - Prepaid expenses 283 51 Grant receivable 1,063 1,044 Other current assets 316 856 Total current assets 11,748 14,733 Right-of-use assets 1,431 2,201 Property, plant and equipment, net 85 125 Other assets 1,683 1,158 Total assets$ 14,947 $ 18,217 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities Accounts payable$1,963 $2,497 Accrued expenses 1,724 1,755 Lease liability 1,274 1,162 Common stock warrant liabilities 463 191 Total current liabilities 5,424 5,605 Lease liability, net of current portion 365 1,340 Other noncurrent liabilities 50 50 Total liabilities 5,839 6,995 Total stockholders' equity 9,108 11,222 Total liabilities and stockholders' equity$ 14,947 $ 18,217 Vincerx Pharma, Inc.Condensed Consolidated Statements of Operations(unaudited)(in thousands, except per share amounts) For the three months ended For the nine months ended September 30, September 30, 2024 2023 2024 2023 Operating expenses: General and administrative$3,885 $3,508 $10,419 $11,816 Research and development 3,908 6,101 12,218 25,260 Total operating expenses 7,793 9,609 22,637 37,076 Loss from operations (7,793) (9,609) (22,637) (37,076) Other income (expense) Change in fair value of warrant liabilities (331) 112 (272) 12 Interest income 154 260 410 1,053 Other income (expense) 127 230 419 804 Total other income (expense) (50) 602 557 1,869 Net loss $ (7,843) $ (9,007) $ (22,080) $ (35,207) Net loss per common share, basic and diluted$(0.17) $(0.42) $(0.63) $(1.66) Weighted average common shares outstanding, basic and diluted 45,672 21,345 35,175 21,269