A Single Arm Phase II Study Combining CRLX101, a Nanoparticle Camptothecin, With Enzalutamide in Patients With Progressive Metastatic Castration Resistant Prostate Cancer Following Prior Enzalutamide Treatment

Background:
Some prostate cancer keeps growing even when testosterone in the body drops to very low levels. This is called castrate-resistant prostate cancer. One treatment is enzalutamide. This is a modern hormonal therapy. But it only works for a certain amount of time and then the cancer becomes resistant to it. Researchers want to see if adding the treatment CRLX101 (formerly IT-101) could make enzalutamide work again for people who have already had it.
Objective:
To test a new way of treating prostate cancer using CRLX101 plus enzalutamide in people with certain prostate cancer who already had enzalutamide treatment.
Eligibility:
Adults ages 18 years and older with metastatic, castration-resistant prostate cancer who have had enzalutamide treatment
Design:
Participants will be screened with a medical history and physical exam. They will have blood and urine tests. They will have a scan of the chest/abdomen/pelvis. They will have a bone scan.
Participants will get treatment in cycles. A cycle lasts 28 days. They will take enzalutamide by mouth once a day. They will get CRLX101 through an intravenous (IV) every 1 or 2 weeks.
Participants will repeat screening tests throughout the study.
Participants will have a follow-up visit 3-4 weeks after they stop taking the study drug. They will repeat most screening tests and have an electrocardiogram.

开始日期2019-03-26

申办/合作机构

National Cancer Institute

NCT02648711

/ Terminated临床1期

Evaluation of an Alternative Schedule for CRLX101 Alone in Combination With Bevacizumab and in Combination With mFOLFOX6 in Subjects With Advanced Solid Tumor Malignancies

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of weekly dosing of CRLX101 (both as monotherapy; (Schedule 1) and in combination with bevacizumab every 2 weeks (Schedule 2) and weekly with a 3 week on / 1 week off schedule in combination with mFOLFOX6 (Schedule 3) to affirm the dose for future clinical studies.

开始日期2015-10-01

申办/合作机构

NewLink Genetics Corp.

NCT02389985

/ Terminated临床1/2期

A Phase Ib/II Study of CRLX101 in Combination With Weekly Paclitaxel in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

The purpose of this study is to estimate the maximum tolerated doses (MTD) of CRLX101 when administered in combination with weekly paclitaxel in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.
Determine through pharmacokinetic evaluation(sometimes described as what the body does to a drug, refers to the movement of drug into, through and out of the body-the time and course of its absorption, bioavailability, distribution, metabolism, and excretion) whether or not the disposition of paclitaxel is affected by the concurrent administration of CRLX101.

开始日期2015-07-01

申办/合作机构

NewLink Genetics Corp.

100 项与 Camptothecin(Calando Pharmaceuticals, Inc.) 相关的临床结果

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100 项与 Camptothecin(Calando Pharmaceuticals, Inc.) 相关的转化医学

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100 项与 Camptothecin(Calando Pharmaceuticals, Inc.) 相关的专利（医药）

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项与 Camptothecin(Calando Pharmaceuticals, Inc.) 相关的文献（医药）

2025-06-01·Current medicinal chemistry

Clinical Outcomes and Effectiveness of CRLX101 for Solid Tumors: A Systematic Review and Meta-analysis

Article

作者: Shamaeizadeh, Nahal ; Sadeghi, Erfan ; Varshosaz, Jaleh

Background::

While it has been demonstrated that delivery of cytotoxic chemotherapy using nanoparticles greatly improves patient drug tolerance and reduces toxicity when compared to the standard formulation, the crucial question of whether they also increase anticancer efficacy remains. The CRLX101 is a nanoparticle composed of cyclodextrin and 20(S)-camptothecin cytotoxic chemotherapy.

Objective::

In order to compare the efficacy of the CRLX101 to its corresponding traditional formulation, we carried out this systematic literature search for randomized clinical and non-randomized trials.

Methods::

Multiple electronic databases, including PubMed, Scopus, Embase, Web of Science, the Cochrane Library, and clinicaltrials.gov, were used to conduct a thorough literature search. By employing a technique akin to a random-effects model, the median of the study-specific was taken into account as the pooled median estimate with a 95% confidence interval.

Results::

Finally, nine clinical studies were chosen for the meta-analysis. The treatment and control groups' overall survival were examined in five and three trials, respectively. Additionally, six out of nine trials and two out of nine trials, respectively, examined the treatment and control groups for progression-free survival (PFS). Meta-analysis revealed that the treatment group had a lower median overall survival (OS) but a greater median progression-free survival than the control group.

Conclusion::

Our meta-analysis shows that CRLX101 outperforms camptothecin in PFS despite its inferior OS. Unresolved pharmacology limits carrier-mediated drug therapeutic application. Carrier-mediated dosages may differ from normal formulations because they are rarely studied.

2025-02-01·ANTICANCER RESEARCH

Camptothecin Triggers Apoptosis in Human and Mouse Drug-resistant Glioblastoma CellsviaROS-mediated Activation of the p53-p21-CD1/CDK2-E2F1-Bcl-xL Signaling Axis

Article

作者: Lin, Chien-Ju ; Cherng, Yih-Giun ; Chen, Jui-Tai ; Chen, Ruei-Ming ; Wu, Gong-Jhe ; Liu, Shing-Hwa

BACKGROUND/AIM:

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Temozolomide (TMZ) is the first-line treatment for GBM. However, most patients with GBM develop drug resistance. Our previous study showed the effects of camptothecin (CPT) and CRLX101, a nanoparticle of CPT, in suppressing GBM growth by targeting drug-sensitive glioblastoma cells. This study evaluated the effects of CPT on drug-resistant glioblastoma cells and explored the underlying molecular mechanisms.

MATERIALS AND METHODS:

Expression of type I topoisomerase (Topo-1) gene in GBM was analyzed using the UALCAN database. Human U87MG-R and mouse GL261-R TMZ-resistant glioblastoma cells were developed. After CPT treatment, apoptotic events were successively determined. The role of the p53-p21-cyclin D1 (CD1)/cyclin-dependent kinase 6 (CDK6)-E2F1-Bcl-xL signaling axis was subsequently investigated.

RESULTS:

The expression of Topo-1 gene was up-regulated in human GBM compared to normal human brains. Treatment of human U87MG-R cells with CPT decreased cell viability. Sequentially, exposure to CPT led to activation of caspase-3, fragmentation of chromosomal DNA, and cell apoptosis. Furthermore, intracellular reactive oxygen species (iROS) were augmented following CPT treatment. Suppression of iROS production concurrently alleviated CPT-triggered apoptotic insults. CPT enhanced the levels of p53, phosphorylated p53, and p21. In contrast, levels of CDK6, CD1, E2F1, and Bcl-xL were decreased by CPT. Attenuating p53 transactivation activity using pifithrin-α also mitigated the CPT-induced apoptosis. The effects of CPT on killing drug-resistant glioblastoma cells were further confirmed in mouse GL261-R cells.

CONCLUSION:

CPT could effectively induce apoptosis in drug-resistant glioblastoma cells via iROS-mediated activation of the p53-p21-CD1/CDK6-E2F1-Bcl-xL axis.

2024-04-01·International journal of pharmaceutics

Multifunctionality of cyclodextrin-based polymeric nanoparticulate delivery systems for chemotherapeutics, combination therapy, and theranostics

Review

作者: Di Martino, Piera ; Gigliobianco, Maria Rosa ; Censi, Roberta ; Casadidio, Cristina ; Devi, Lakshmi Sathi

As cancer being the most difficult disease to treat, different kinds of medications and therapeutic approaches have been prominently developed by scientists. For certain families of drugs, such as immuno-therapeutics or antibody-drug conjugates, efficient delivery systems are required during administration to protect the drugs from chemical degradation or biological inactivation. Delivery systems with the ability to carry different therapeutics or diagnostic agents or both, hold promising potential to tackle the abnormalities behind cancer. In this context, this review provides updated insights on how cyclodextrin-based polymeric nanosystems have become an effective treatment approach against cancer. Cyclodextrins (CDs) are natural oligosaccharides that are famously exploited in pharmaceutical research due to their exceptional quality of entrapping water-insoluble molecules inside their hydrophobic core and providing enhanced solubility with the help of their hydrophilic exterior. Combining the properties of CDs with polymeric nanoparticles (PNPs) brings out excellent versatile and tunable profiles, thanks to the submicron-sized PNPs. By introducing the significance of CD as a delivery system, a collective discussion on different binding approaches and release mechanisms of CD-drug complexation, followed by their characterization studies has been done in this review. Further, in light of recent studies, the article majorly focuses on conveying how promoting CD to a polymeric and nanoscale elevates the multifunctional advantages against cancer that can be successfully applied in combination therapy and theranostics. Moreover, CD-based delivery systems including CALAA-01, CRLX101, and CRLX301, have demonstrated improved tumor targeting, reduced side effects, and prolonged drug release in preclinical studies and clinical trials.

项与 Camptothecin(Calando Pharmaceuticals, Inc.) 相关的新闻（医药）

2024-11-12

·GlobeNewswire-Health Care

Vincerx Pharma Reports Third Quarter 2024 Financial Results

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

临床1期临床结果财报抗体药物偶联物

2024-08-09

·药融圈

纳米药物的治疗应用：最新进展和未来展望（上）

▲8月15-16日苏州2024生物医药创新者峰会扫码报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。摘要：近几十年来，纳米医学的概念有了显著的发展，利用了被称为增强渗透性和滞留（EPR）效应的独特现象。通过将纳米技术原理整合到医学中，这促进了靶向药物递送、成像和个体化治疗的重大进步。许多纳米药物已经被开发并应用于疾病治疗，特别是癌症治疗。最近，纳米医学已经应用于各种先进领域，包括诊断、疫苗、免疫治疗、基因递送和组织工程。多功能纳米药物促进同时给药、治疗监测和成像，允许即时反应和个性化治疗计划。本文综述了纳米材料的主要进展及其在生物和医学领域的潜在应用。与此同时，我们还提到了纳米医学的各种临床转化，以及纳米医学目前在克服临床转化障碍方面所面临的主要挑战。关键词：纳米医学应用；免疫疗法；治疗的；疫苗开发；基因治疗；组织工程 1. 介绍 1959年，物理学家理查德·费曼在一次关于在原子和分子水平上创造物体的演讲中首次提出了纳米技术的概念。如今，科学家们相信纳米技术是21世纪最有前途的技术进步。他们将其作为一种潜在的研究医疗条件的新方法进行研究。在过去十年中，用于纳米技术研究和开发的公共资金有所增加，这表明纳米技术将迎来一个生产力和繁荣的新时代[1]。此外，纳米医学的应用开辟了以前未开发的潜力，特别是在癌症治疗方面。它提供了精确的靶向，提高了疗效，减少了不良反应。许多纳米颗粒（NPs），包括脂质体、聚合物NPs和无机NPs，现在在治疗领域提供了益处，包括改善的体外和体内药物稳定性、治疗效果和表面修饰的简易性[2]。最近，生物特异性分子现在可以通过化学或物理技术与NP结合，并且NP可以用于某些生物事件的利用，例如抗体-抗原相互作用、受体-配体相互作用和DNA-DNA杂交[3]。为了将药物输送集中在目标区域并防止酶降解，可以制造工程纳米颗粒（NPs）来控制药物释放并靶向或避免与不同细胞的特定相互作用[2]。尽管纳米颗粒介导的递送方法解决了上述许多问题，但在使用它们时，特别是在纳米颗粒设计方面，有几件事要记住。粒子尺寸、形状、疏水性和表面电荷都对纳米颗粒如何到达目标有敏感的影响。大的纳米颗粒（>100nm）可滞留在细胞外基质（ECM）中，而小的纳米颗粒（<5nm）可在循环过程中从血管中漏出。另一方面，从大约5到100nm的中等大小的纳米颗粒滞留在血流中，并被有效地运输到靶位点。颗粒形状（以及大小）是影响纳米颗粒从淋巴结排出的重要因素。以前的大多数纳米颗粒配方都是球形的，但由于纳米颗粒工程的进步，最近已经生产出了各种不同的形式，包括棒状、棱柱状、立方体、星形和圆盘状。除了颗粒大小和形状，载体的表面电荷对于细胞内化和免疫反应激活也很重要。表面电荷可能对细胞吸收纳米颗粒的能力产生影响。与中性或带负电的纳米颗粒相比，带正电的纳米颗粒通常会引发更强的免疫反应。然而，因为它们经常被捕获在带负电荷的ECM中，所以带正电荷的纳米颗粒显示出降低的组织渗透性[4]。因此，与常规疗法相比，特定工程纳米颗粒可以提供各种益处，包括保护治疗有效载荷免于生物降解，通过主动靶向来靶向肿瘤细胞，这将使脱靶正常细胞毒性最小化，并增强体内稳定性和生物利用度，并且这种纳米颗粒已经被巧妙地编程以在感兴趣的位点释放其有效载荷[5]。此外，纳米材料的具体应用取决于其表面化学（组成）、表面物理（形貌和粗糙度）、表面热力学（润湿性和自由能）和毒理学效应[3]。在纳米医学应用领域，主要焦点是癌症治疗，利用增强的渗透性和滞留效应（EPR）[6]。EPR效应的历史、机制和未来影响在各种文章和书籍章节中都有详尽的记载[6-12]。这种效应在纳米药物在肿瘤组织内的选择性积聚中起着至关重要的作用，增强了其有效性，同时最大限度地减少了全身暴露和副作用。从本质上讲，EPR效应是指在肿瘤血管独特的解剖和病理生理特征的促进下，大分子药物在肿瘤组织中选择性积聚的现象。这允许大分子药物在全身给药后优先渗透和滞留在实体瘤内。EPR效应的有效性不仅在实验动物模型中得到了证实，而且在人类中也得到了证实，包括肝癌、肾癌和转移性乳腺癌[13-15]。最近对人类肾肿瘤和转移性乳腺癌的研究表明，在超过87%的样本中存在显著的EPR效应，突出了这种效应在抗癌纳米药物进展中的关键作用[13,14]。基于EPR效应，纳米药物表现出许多对靶向癌症治疗有益的特性，而常规小分子抗癌药物则倾向于在正常组织和器官中不加选择地扩散，从而导致全身性不良反应[7,8,10]。因此，纳米药物在改善治疗选择方面提供了希望。20世纪90年代，第一个聚合物共轭纳米药物SMANCS（苯乙烯马来酸聚合物共轭新制癌素）在日本获得批准，标志着抗癌纳米药物发展的一个重要里程碑[15]。在过去的二十年里，抗癌纳米药物领域经历了巨大的发展和进步[16-18]。许多纳米药物目前正在临床环境中使用，许多其他药物正在进行临床试验（见表1)。近年来，许多纳米药物被设计和开发用于先进的、侵入性较小的癌症治疗。实例包括基于纳米探针的光动力疗法[12, 19]和硼中子俘获疗法（BNCT）[20, 21]，以及使用磁铁矿的磁热疗[12, 19]，所有这些都显示出有希望的治疗潜力。此外，纳米医学在免疫治疗、基因治疗、预防医学等前沿生物医学领域的应用也取得了重要进展。表1. 抗癌纳米药物的实例重要的关注。一个显著的例子是Covid-19的mRNA疫苗的成功，其利用脂质纳米颗粒作为递送系统[22]。在此背景下，本综述探讨了纳米药物在先进癌症治疗和其他生物医学领域的应用前景，如图1所示。图1. 纳米药物在各种生物医学和治疗领域的新应用通过对基本思想、当前发展和潜在未来方向的解释，我们强调了纳米医学通过其先进特性的影响，引导我们进入精准医疗和更好的患者结果的新模式。 1.1.纳米药物在光动力疗法中的应用 1.1.1. 纳米设计的光敏剂，一种有前途的癌症治疗方法尽管肿瘤治疗方法不断扩展，但仍存在重大挑战，包括非特异性、耐药性、低应答率和严重的毒性相关副作用[23]。光动力疗法（PDT）提供了一种非侵入性和靶向性的替代方法，其中光活化的光敏剂（PS）产生活性氧（ROS），导致肿瘤细胞死亡。PDT有望成为解决传统肿瘤治疗策略缺点的有效方法[24]。然而，由于缺乏肿瘤选择性，传统光敏剂的局限性阻碍了PDT的临床转化，导致其在当前临床实践中的应用相对有限[25]。在这方面，纳米光敏剂（NanoPs）的出现是一种克服这些挑战的手段，它利用增强的渗透和滞留（EPR）效应来靶向肿瘤，为增强PDT的功效和特异性提供了巨大的潜力[19]。此外，因为大多数PSS表现出荧光性质，所以可以通过荧光成像，即光动力学诊断（PDD）来区分肿瘤和正常组织。 1.1.2. 用于肿瘤靶向的纳米粒子与传统的PS相比，纳米SS由于其纳米级尺寸和表面修饰而表现出优越的肿瘤靶向能力[26]。纳米粒子表面可进一步被特异性靶向配体或抗体功能化，使其能够特异性识别和结合肿瘤细胞，从而增强治疗效果并最大限度地减少对正常组织的损伤[26]。通过EPR效应介导的被动积累和使用配体或抗体的主动靶向等策略，纳米粒子可以在肿瘤内精确定位，最大限度地减少脱靶效应并增强治疗效果[27]。此外，纳米材料的光学性质可以通过控制其形态、尺寸和结构来调节，使光敏剂在特定波长下的吸收最大化，从而提高PDT效率并实现更精确的肿瘤治疗[28]。 1.1.3. 光动力疗法的临床应用及纳米材料的应用前景在过去的二十年里，与PDT相关的临床研究发展迅速，目前已有多个PS被批准用于临床治疗。例如，氨基酮戊酸甲酯（MAL）[29]和5-ALA[30]已被美国食品和药物管理局（FDA）批准分别用于治疗光化性角化病、基底细胞癌（BCC）、浅表性和结节性基底细胞癌以及鳞状细胞癌（SCC）。Radachlorin®还获得了俄罗斯联邦卫生部（MHRF）的批准，用于治疗皮肤癌[31]。欧洲药品管理局（EMA）已批准替莫泊芬用于晚期头颈部鳞状细胞癌的姑息治疗[32]。PDT在皮肤恶性肿瘤，特别是非黑色素瘤皮肤癌如基底细胞癌和鳞状细胞癌的治疗中具有相对成熟的应用基础[33]。其局部治疗方法不仅产生了良好的美容效果，减少了对患者外观的影响，而且还表现出良好的抗肿瘤效果和较低的复发率[34]。在胸部恶性肿瘤领域，PDT作为一种重要的治疗方式，已被批准并广泛应用，尤其是早期非小细胞肺癌[35]。在各种其他领域，如头颈部恶性肿瘤、泌尿生殖系统恶性肿瘤、乳腺恶性肿瘤[36]、颅内恶性肿瘤[37]和胃肠道恶性肿瘤，PDT已显示出广泛的潜力。随着新型纳米光敏剂的合理设计，例如使用超小纳米材料克服血脑挑战，PDT在脑肿瘤治疗中的前景越来越广阔[38]。此外，PDT治疗包括卵巢癌、子宫内膜癌、宫颈癌、骨肉瘤和恶性血液病在内的各种恶性肿瘤的临床研究也在积极进行中。随着研究的不断深入，光动力疗法在临床应用前景广阔。扩大癌症治疗的范围。总之，PDT作为一种局部治疗模式，结合新型光敏剂和纳米技术的发展，有可能为治疗各种恶性肿瘤带来更加个性化和精确的选择，进一步改善治疗结果，提高患者生存率和生活质量。 1.1.4. 利用纳米材料的多功能治疗策略纳米材料的不断发展赋予了某些类型的纳米材料不仅具有光敏性，还具有声敏性和光热特性[39, 40]。这些特点使PDT能够与声动力疗法（SDT）或光热疗法（PTT）相结合，提供足够的灵活性，与其他治疗模式相结合，以实现协同效应[41, 42]。例如，Liao等人的研究。已经发现二氢卟酚E6表现出有效的光敏性和声敏性，在声动力疗法联合PDT中起着至关重要的作用[43]。此外，利用纳米粒子共同递送化疗药物、免疫调节剂或基因治疗剂能够实现多模式癌症治疗策略[44]。此外，将成像探针集成到纳米系统中可以实时监测治疗反应，促进个性化治疗方法[45]。表2 总结使用纳米粒子的治疗策略和挑战。表2. 纳米粒的应用及治疗策略 Abbreviations: polymer-modified nanophotosensitizers (PNPSs); metal nanoclusters-based photosensitizers (MNPSs); carbon nanophotosensitizers (CNPSs); quantum dot photosensitizer (QDPSs); upconversion nanoparticles (UCNPs); metal-organic frameworks (MOFs); covalent organic frameworks (COFs); photothermal therapy (PTT); photodynamic diagnosis (PDD). 1.1.5. 挑战与未来展望纳米材料在癌症治疗中的广泛应用已经取得了长足的进步，不仅在基础研究中，而且在临床研究中都显示出显著的疗效。癌症治疗的疗效与多种因素密切相关，例如纳米粒子本身的特性、其在生物体中的转运过程以及细胞靶标损伤。这些因素包括药物小分子的负载和功能修饰、纳米药物的体内转运和肿瘤积聚、肿瘤内渗透和微环境控制释放以及对肿瘤细胞的特异性损伤和正常组织的生物安全性[68]。然而，尽管取得了重大进展，纳米介导的PDT的广泛临床应用仍然面临着一些挑战。这些挑战包括对生物相容性、长期安全性、合成方法的标准化和监管审批程序的关注。未来的研究方向可能集中于开发多功能纳米粒子平台，完善靶向策略和优化治疗方案，研究药物在体内不同治疗阶段的转运和作用机制，以最大限度地提高治疗效果，同时最大限度地减少不良反应。总的来说，目前批准用于临床的纳米材料相对较少，大多数仍处于基础研究或临床试验阶段。随着研究的进展，越来越多的临床实验已经开始。可以预见，随着纳米粒子在PDT抗肿瘤治疗基础研究的快速发展，未来将会有更多的相关临床试验，力争将更多的纳米粒子应用于临床。 1.2.纳米药物在免疫治疗中的应用免疫疗法始于19世纪，当时观察到一些肉瘤患者在化脓性链球菌感染后出现肿瘤消退。这导致使用科利毒素治疗一些肉瘤患者，在一些患者中偶尔出现完全反应[69]。免疫治疗的目的是利用宿主的免疫反应来达到持久的治疗效果。然而，免疫治疗的严重副作用可能诱发自身免疫性和非特异性炎症[70]，目前仍难以控制。近几十年来，无论是合成的还是天然产生的NPs，由于其独特的物理和化学特性，已成为免疫治疗领域大量研究的主题[71]。通过使用纳米药物和生物材料，有可能将免疫调节剂以靶向方式递送到所需位置，具有许多优点，如改善药代动力学、提高治疗效果和最小化剂量依赖性全身毒性[5,70]。为了最大限度地发挥免疫治疗药物的效力，应对NP进行适当改造，使其优先从给药部位靶向感兴趣的区域（胃肠外或粘膜疫苗接种途径是常见的给药途径）。下面提到的各种策略正被用于增强纳米药物的免疫原性效果。 1.2.1. 靶向肿瘤免疫微环境使用改变肿瘤免疫微环境（TIME）的纳米药物是提高抗癌免疫疗法有效性的关键策略[72]。缺氧是由于肿瘤细胞在时间内迅速膨胀，血管扭曲变形所致。这导致免疫抑制细胞的积聚，如调节性T细胞（Tregs）和髓源性抑制细胞（MDSCs），以及免疫抑制因子如转化生长因子β（TGF-β）和血管内皮生长因子（VEGF）的分泌，最近显示其抑制树突状细胞成熟和T细胞浸润。通过关注当时的主要元素，纳米颗粒可能会改变癌细胞周围的免疫抑制环境。此外，增强细胞毒性 T 细胞等效应免疫细胞的浸润、增殖、成熟、存活和/或活化，可通过阻断 TIME 中的免疫抑制，提高免疫疗法的效果[72，73]。Chen等人[74]使用白蛋白包被的MnO2制备pH/H2O2双重响应性纳米颗粒。氧是由MnO2穿透肿瘤时与H2O2和H+反应产生的。通过减少缺氧状态，他们提高了光动力治疗和化疗的有效性。此外，肿瘤相关巨噬细胞（TAMs）是 TIME 的主要参与者，它们在肿瘤萌发阶段启动抗肿瘤免疫；然而，一旦肿瘤形成，它们就会在肿瘤血管生成、免疫抑制、侵袭和转移中发挥作用。这种差异可能源于巨噬细胞的延展性，导致TAMs从M1极化状态转变为M2极化状态[73, 75]。伦纳德等人使用载有CRISPR复合物的脂质体来沉默哺乳动物雷帕霉素靶蛋白（mTOR）通路，这是一种参与许多重要生理功能（如细胞生长、增殖和自噬）的重要细胞信号通路。这导致巨噬细胞从M2表型极化到M1表型，从而提高化疗的治疗效果[70]。 1.2.2. 靶向和重编程T细胞 T细胞是适应性免疫应答所必需的，并且是淋巴细胞的一部分。免疫介导的细胞死亡是T细胞的作用之一。T细胞可分为两种主要亚型：CD8+和CD4+ T细胞。细胞毒性T细胞，通常称为CD8+ T细胞，特异性破坏癌细胞和病毒感染细胞。相反，CD4+ T细胞通过细胞因子影响其他免疫细胞；或者，通过决定免疫系统是否以及如何对感知到的威胁做出反应，它们间接导致了受感染细胞的死亡。由于T细胞表面含有多种细胞标记，并参与包括癌症在内的多种疾病的免疫应答，因此有多种靶向方法可用于治疗不同的疾病[76]。使用RNA干扰（RNAi）下调特定基因并修饰T细胞活性，对于开发针对多种免疫相关疾病（如癌症、炎症、自身免疫和病毒感染）的定制疗法具有很大的前景。Ramishetti等人描述了一种独特的方法，该方法使用靶向脂质NPs（TLNPs）将siRNA精确递送至小鼠CD4+ T细胞。使用抗CD4单克隆抗体使TLNP表面功能化，允许siRNA仅递送至CD4+ T细胞。TLNPs在体内表现出选择性，只关注原代CD4+T细胞而忽略其他细胞类型。这些TLNP已与几种脂质合成，以增强siRNA递送的稳定性和功效，从而提高其功效[77]。此外，活化的T细胞（ATCs）表达更多的转铁蛋白受体，表明ATCs可以用该技术靶向。所以，谢等人。创建了一种包含转铁蛋白-聚乙烯亚胺（Pei）和siRNA的多聚体作为靶向递送系统，以抑制与炎症ATCs相关的基因。他们还证实了Polyplex治疗哮喘的潜力[76]。免疫细胞重新编程的劳动密集型过程使Yescarta的CAR-T治疗成本增加到373，000美元，Kymriah的CAR-T治疗成本增加到475，000美元。然而，纳米技术提供了负担得起的纳米载体，可以精确和快速地将肿瘤识别能力编程到宿主T细胞中，从而解决这些问题。它们与靶向淋巴细胞的配体联合使用，将肿瘤特异性CAR货物递送到T细胞中。摄入后，这些NP指导足够量的效应细胞诱导肿瘤消退，其抗癌免疫特性类似于现有的CAR-T技术，通常在体外转导培养的T细胞[78]。 1.2.3. 活化增强NK细胞先天免疫系统的第一道防线由自然杀伤（NK）细胞组成，NK细胞对于识别癌细胞和抵御病毒感染至关重要。NK细胞占人类外周血中所有淋巴细胞的5%至20%[79]。尽管基于NK细胞的免疫疗法非常有前景，但它仍然遇到了一些重大障碍，如NK细胞增殖有限和体内寿命短，以及昂贵的治疗费用和复杂的输送系统[80]。然而，基于NP的疗法试图通过选择性激活NK细胞来克服这些障碍。根据Chandrasekaran等人[81]，通过与肿瘤引流淋巴结（TDLN）内的NK细胞偶联的TRAIL修饰的脂质体抑制小鼠的皮下肿瘤转移。此外，他们发现用TRAIL功能化的NK细胞延长了其在TDLN中的滞留时间，从而导致肿瘤细胞发生凋亡。后来，Gao等人[82]创建了具有二硒醚修饰的RGD肽的聚合NP，其靶向肿瘤，允许用于肿瘤积聚的全身注射和用于NK细胞介导的癌症免疫疗法的辐射暴露。基于给药方式，碳纳米管（CNT）也可能具有免疫抑制作用。在C57BL/6成年小鼠中，吸入CNT导致T细胞增殖减少，NK细胞活性降低，脾脏中IL-10（一种抗炎细胞因子）的基因产生增加。这导致了小鼠的系统性免疫抑制。此外，与感染呼吸道合胞病毒的小鼠相比，鼻内给予金纳米棒可减少TNF-α、GM-CSF、IL-17和IL-12p70，并增加IL-9[83]。在另一项研究中，使用双特异性抗体（SS-FC、抗CD16和抗CEA）包被钌NPs，刺激NK细胞引起坏死和凋亡，进而进一步激活免疫反应[84]。 1.2.4. 激活NKG2D受体 NKG2D是一种类似于C型凝集素的活化受体，广泛表达于CD8+ T、γδT、NK和NKT细胞。小鼠UL-16结合蛋白（ULBP）样转录物1、H60和维甲酸早期诱导转录物-1（Rae-1）是NKG2D配体。由于大多数正常组织缺乏被病毒感染或肿瘤细胞强迫表达的NKG2D配体，这些配体在免疫治疗中作为肿瘤靶向抗原发挥作用[85]。TGF-β抑制剂和硒代半胱氨酸纳米乳通过增敏NKG2D配体增强NK细胞的裂解能力。TGF-β抑制剂成功阻断TGF-β/TGF-βRI/Smad2/3信号通路，导致肿瘤细胞表面NKG2D配体数量增加。在γδT淋巴细胞中，硒半胱氨酸抑制PD-1表达，同时促进NKG2D受体的产生[84]。另一项研究表明，包被有小鼠和人片段可结晶（FC）-融合NKG2D（FC-NKG2D）的NKG2D/NPs可以通过剂量依赖性磁细胞分选，在体外靶向多种NKG2D配体阳性肿瘤类型。NKG2D/NPs可以靶向多种肿瘤类型，并且肿瘤靶向氧化铁NPs（IONP）研究的概念验证阶段可以通过磁分离平台进行辅助[86]。 1.2.5. 靶向抗原呈递细胞巨噬细胞、树突状细胞（DC）和B淋巴细胞是抗原呈递细胞（APC）的例子，它们是先天免疫系统的组成部分，并且对于启动和控制适应性应答是至关重要的。其主要职责是识别、捕获和消化抗原。在过去的20年里，抗原靶向策略作为传染病、自身免疫和癌症的预防和治疗措施得到了广泛的研究。这些策略旨在通过抗原捕获机制提高疫苗效率[87]。NPS表面的抗原呈递类似于病毒呈递抗原的自然方式，通过控制和延迟抗原的释放，NPS可以调节免疫系统对其的暴露。此外，同时加载抗原和佐剂可以通过NPs提高大多数蛋白质的限制性免疫原性。在这方面，聚合物NP在已引入用于负载和抗原递送的各种纳米载体中引起了关注。已经检测了各种类型的聚合物，例如聚酯、聚（α-羟基酸）、蛋白质和多糖。明胶具有最小的免疫原性，也是一种很好的疫苗纳米载体。在这方面，卵清蛋白（OVA）和破伤风类毒素等抗原被固定在明胶 NPs（GNPs）表面，通过改变抗原的负载方法和 NPs 的表面特性，可以操纵对抗原的免疫反应[88]。此外，通常将PEG添加到NPs中以减少其与网状内皮系统的相互作用[89]。 1.2.6. 作为免疫检查点抑制剂的载体免疫细胞的表面蛋白被称为免疫检查点，其功能是通过多种抗原对免疫系统的激活进行负调节。免疫检查点分子在肿瘤细胞和免疫细胞上广泛表达[5,90]。然而，缺乏理想的免疫治疗方法（IMT）、免疫相关不良事件（IRAEs）和低应答率限制了使用创新免疫检查点抑制剂（ICIs）进行联合治疗的研究。核动力源已成为促进跨学科合作的有效工具。通过NPS有针对性地提供ICIS既可行又有效；它消除了主要障碍，提高了治疗效果，并证明了进一步临床研究的合理性[90]。基于脂质的NPs（脂质体和LNPs）在临床试验中越来越多地用于递送RNA和免疫治疗药物，但其在ICIS中的应用并没有跟上需求[90]。 1.2.7. 纳米免疫治疗的临床进展基于迄今为止取得的进展，纳米免疫疗法在治疗各种疾病方面显示出了良好的前景。这些结果中的大多数仍处于临床前阶段，其中一些已获得FDA批准，目前正在进行临床试验，如表3所示。脂质体、聚合物NPs和PEG-药物结合物目前被批准用于治疗各种免疫疾病[91]。表3. 目前正在进行免疫治疗临床试验的纳米粒的详细信息 1/2/3期临床试验已经评估了ALT-803（靶向NK和T细胞的重组IL-15超激动剂复合物纳米凝胶）用于治疗白血病或晚期实体瘤（例如NSCLC、黑色素瘤、肾癌、结肠癌和乳腺癌）患者的安全性和有效性。LNP-mRNA技术是目前正在进行临床研究的首选纳米制剂[92]，其脂质体复合物允许将治疗性mRNA癌症疫苗靶向递送至淋巴器官中的APC。Nanobiotix创造了Hensify®，以增强局部免疫系统并从物理上杀死恶性肿瘤。Nanobiotix正在进行多项临床试验，并已获得美国FDA批准，开始使用PD-1和NBTXR3抗体治疗肺癌的联合试验[5]。截至2023年，抗PD-1/PD-L1和放射治疗以及NBTXR3正在进行1期和2期临床试验，以帮助治疗晚期实体恶性肿瘤患者（NCT05039632））。此外，正在进行一项新型RNA-纳米颗粒疫苗的临床试验，用于治疗辅助抗PD-1抗体治疗后的早期黑色素瘤复发，以评估肿瘤特异性RNA-NP疫苗接种在接受辅助抗PD1（A-PD1）治疗的IIB-IV期黑色素瘤患者中的安全性和生存能力（NCT05264974）。 III期临床试验正在评估Tecemotide，一种MUC1特异性癌症免疫疗法，用于治疗IIIA/IIIB期NSCLC。一种名为Lipovaxin-MM的树突状细胞靶向脂质体疫苗也开始了恶性黑色素瘤的1期临床试验。基于环糊精聚合物纳米颗粒（CDP）技术，CRLX101是一流的纳米药物，具有将治疗转化为积极临床结果的潜力[93]。 1.2.8. 挑战和前景尽管人们对基于NP的免疫疗法越来越感兴趣，但这些免疫刺激性NP的临床转化仍然存在重大问题。在评估NPs的毒性时，重要的是要考虑这样一个事实，即它们中的一些可能会改变细胞内的信号通路。当NP与血清蛋白相互作用时，免疫系统可以将它们识别为外来物质，并产生针对它们的自身免疫反应。因此，为了在临床环境中成功使用NP，必须将其设计为能够防止ROS、超敏反应或过敏性致敏的产生，并易于从体内清除[101]。采用的主要障碍是对纳米颗粒与生物分子的作用模式的理解不足。这导致一些纳米制剂退出市场，甚至在获得FDA批准后也是如此。其中的一些例子包括Feridex I.V.（Endorem，Ferumoxides）、Lumirem（Gastromark）、Resovist（Cliavist）、Sinerem（Combidex）和Clariscan（PEG-Fero，Feruglose NC100150）[93]。参考文献 1. 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Front. Oncol. 2018, 8, 404. 版权声明：本文转自百奥信康，如不希望被转载的媒体或个人可与我们联系，我们将立即删除扫码报名参会【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

基因疗法疫苗免疫疗法核酸药物

2024-08-08

·GlobeNewswire-Health Care

Vincerx Pharma Reports Second Quarter 2024 Financial Results

Vincerx continues to enroll its Phase 1 studies of antibody-drug conjugate (ADC) VIP943, with data expected by the end of Q4 2024, and small molecule drug-conjugate (SMDC) VIP236, with data expected at the end of Q3 2024 Expected cash runway through 2024 PALO ALTO, Calif., Aug. 08, 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 second quarter of 2024 and provided an overview of its clinical programs and anticipated milestones. “During the second quarter, our team focused on execution and the continued enrollment of patients in our ongoing Phase 1 studies for our potentially best-in-class ADC, VIP943, and first-in-class SMDC, VIP236,” said Ahmed Hamdy, M.D., Chief Executive Officer. “We look forward to evaluating the results from additional cohorts and sharing data by end of Q3 for VIP236 and by end of year for VIP943.” SECOND QUARTER 2024 CLINICAL PROGRAM HIGHLIGHTS AND ANTICIPATED MILESTONES VIP943 VIP943, a novel CD123-targeted ADC created from Vincerx’s VersAptx™ platform, consists of an anti-CD123 antibody, a unique linker cleaved intracellularly by legumain, and a novel kinesin spindle protein inhibitor (KSPi) payload enhanced with Vincerx’s CellTrapper® technology. Its next-generation effector chemistry was designed to address challenges associated with many ADCs by improving efficacy and reducing severe toxicities.Vincerx expects to share additional Phase 1 study data for VIP943 for patients with relapsed/refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and B-cell acute lymphoblastic leukemia (B-ALL) (NCT06034275) by the end of Q4 2024. VIP236 VIP236 is an αVβ3 SMDC conjugated to an optimized camptothecin (CPT) payload created from Vincerx’s VersAptx platform. VIP236 is a first-in-class drug designed to deliver its optimized CPT payload directly to tumor tissues to overcome chemotherapy-related side effects. Preclinical studies have shown 11 times more optimized CPT is delivered to the cancerous tissues than found circulating in the blood. In addition, the optimized CPT is designed to limit drug transporter liabilities, a common mechanism for cancer resistance to chemotherapy.Vincerx looks forward to sharing additional data from this Phase 1 study (NTC05371054) by the end of Q3 2024. Enitociclib Enitociclib is a highly selective CDK9 inhibitor designed to block the activation of RNA polymerase II, leading to the reduction 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). At the AACR Advances in Malignant Lymphoma meeting in June 2024, the NIH presented the interim study results previously shared by Vincerx in January 2024 and May 2024. VIP924 VIP924 is a first-in-class CXCR5-targeted ADC created from Vincerx’s VersAptx platform.VIP924 can be evaluated in B-cell malignancies, including mantle cell lymphoma, follicular lymphoma, DLBCL, and chronic lymphocytic leukemia , as a monotherapy and in combination.IND application is anticipated in early 2026, pending funding. VersAptx™ Platform VersAptx is Vincerx’s versatile and adaptable, next-generation bioconjugation platform. The modular nature of this platform enables the combination of different targeting, linker, and payload technologies to develop bespoke bioconjugates to address different cancer biologies. SECOND QUARTER 2024 FINANCIAL RESULTS Vincerx had approximately $16.3 million in cash, cash equivalents and marketable securities as of June 30, 2024, as compared to approximately $5.1 million as of March 31, 2024. Based on its current business plans and assumptions, Vincerx believes its available capital, including the proceeds of its April financing of approximately $16.9 million, will be sufficient to meet its operating requirements through the end of 2024.Research and development expenses for the second quarter ended June 30, 2024 were approximately $3.8 million, as compared to approximately $8.2 million for the same period in 2023. This decrease is primarily the result of decreases in research services of approximately $1.8 million, manufacturing services associated with our ADC program of approximately $1.6 million, and personnel related expenses of approximately $0.8 million.General and administrative expenses for the second quarter ended June 30, 2024 were approximately $3.6 million, as compared to approximately $3.8 million for the same period in 2023. This decrease is primarily driven by decreases in personnel-related expenses of approximately $0.3 million.For the second quarter ended June 30, 2024, Vincerx reported a net loss of approximately $1.8 million, or $0.05 per share. For the second quarter ended June 30, 2023, Vincerx reported a net loss of approximately $11.6 million, or $0.54 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 antibody-drug conjugate, VIP943, in Phase 1; small molecule-drug conjugate, VIP236, in Phase 1; preclinical antibody-drug conjugate, VIP924; CDK9 inhibitor, enitociclib, in an NIH-sponsored Phase 1; and VersAptx, its versatile and adaptable, next-generation bioconjugation platform. Vincerx is based in Palo Alto, California, and has a research facility 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, general economic, financial, legal, political, and business conditions; risks associated with preclinical or clinical development and studies, including those conducted prior to Vincerx’s in-licensing; 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; Vincerx’s capital requirements, availability and uses of capital, and cash runway; and the risks and uncertainties set forth in the Form 10-Q for the quarter ended March 31, 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, CellTrapper, and VersAptx are our trademarks. ContactsGabriela JairalaVincerx Pharma, Inc.gabriela.jairala@vincerx.com Cassidy McClainInizio Evoke CommsCassidy.McClain@inizioevoke.com Vincerx Pharma, Inc.Condensed Consolidated Balance Sheets(in thousands) June 30, 2024 December 31, 2023 (unaudited) ASSETS Current assets: Cash and cash equivalents$7,923 $12,782 Short-term marketable securities 8,396 - Prepaid expenses 530 51 Grant receivable 1,018 1,044 Other current assets 416 856 Total current assets 18,283 14,733 Right-of-use assets 1,693 2,201 Property, plant and equipment, net 98 125 Other assets 1,453 1,158 Total assets$ 21,527 $ 18,217 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities Accounts payable$1,536 $2,497 Accrued expenses 2,428 1,755 Lease liability 1,236 1,162 Common stock warrant liabilities 132 191 Total current liabilities 5,332 5,605 Lease liability, net of current portion 697 1,340 Other noncurrent liabilities 50 50 Total liabilities 6,079 6,995 Total stockholders' equity 15,448 11,222 Total liabilities and stockholders' equity$ 21,527 $ 18,217 Vincerx Pharma, Inc.Condensed Consolidated Statements of Operations(unaudited)(in thousands, except per share amounts) For the three months ended For the six months ended June 30, June 30, 2024 2023 2024 2023 Operating expenses: General and administrative$3,612 $3,811 $6,534 $8,308 Research and development 3,754 8,248 8,310 19,159 Total operating expenses 7,366 12,059 14,844 27,467 Loss from operations (7,366) (12,059) (14,844) (27,467)Other income (expense) Change in fair value of warrant liabilities 5,263 (118) 59 (100)Interest income 157 327 256 793 Other income (expense) 138 300 292 574 Total other income (expense) 5,558 509 607 1,267 Net loss $ (1,808) $ (11,550) $ (14,237) $ (26,200) Net loss per common share, basic and diluted$(0.05) $(0.54) $(0.48) $(1.23)Weighted average common shares outstanding, basic and diluted 38,339 21,274 29,869 21,231

临床1期财报AACR会议抗体药物偶联物

100 项与 Camptothecin(Calando Pharmaceuticals, Inc.) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05899

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性去势抵抗性前列腺癌	临床2期	美国	National Cancer Institute	2019-03-26
复发性卵巢癌	临床2期	美国	NewLink Genetics Corp.	2015-07-01
复发性原发性腹膜癌	临床2期	美国	NewLink Genetics Corp.	2015-07-01
转移性肾细胞癌	临床2期	美国	NewLink Genetics Corp.	2014-07-01
广泛期小细胞肺癌	临床2期	美国	The University of Chicago	2013-01-16
复发性小细胞肺癌	临床2期	美国	The University of Chicago	2013-01-16
食管腺癌	临床2期	美国	City of Hope National Medical Center	2012-11-01
进展期胃腺癌	临床2期	美国	City of Hope National Medical Center	2012-11-01
晚期胃食管交界处腺癌	临床2期	美国	City of Hope National Medical Center	2012-11-01
食管鳞状细胞癌	临床2期	美国	City of Hope National Medical Center	2012-11-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03531827 (CTgov)	临床2期	转移性去势抵抗性前列腺癌	4	enzalutamide+CRLX101	淵憲繭齋鬱廠廠簾醖鏇 = 醖憲齋衊築艱積範選夢獵廠觸艱繭窪蓋選鹽遞 (願艱衊網襯獵製醖選製, 觸憲衊獵構鬱獵網廠鑰 ~ 壓顧艱蓋夢壓餘膚觸鑰) 更多	-	2022-07-12
NCT01652079 (Pubmed) 人工标引	临床2期	复发性卵巢癌	63	CRLX101	築繭壓憲壓鑰選願積願(憲築糧糧築餘築憲積蓋) = 築壓餘選範醖網願廠糧範築醖襯鏇糧鬱範淵淵 (網糧積醖簾衊夢願糧鹽 ) 更多	积极	2021-09-01
				bevacizumab+CRLX101	築繭壓憲壓鑰選願積願(憲築糧糧築餘築憲積蓋) = 糧願艱膚獵壓鹽膚蓋壓範築醖襯鏇糧鬱範淵淵 (網糧積醖簾衊夢願糧鹽 ) 更多
NCT02010567 (Pubmed \| Nanomedicine)	临床1/2期	局部晚期直肠癌新辅助	32	CRLX101	簾艱構範鹽鬱窪醖鹽願(簾醖衊選窪膚餘襯觸窪) = 夢夢艱網衊憲觸夢廠觸選觸夢顧繭糧願醖積築 (淵鏇衊蓋蓋鑰鏇壓範積 ) 更多	-	2019-06-01
NCT01612546 (CTgov)	临床2期	复发性胃癌 \| 进展期胃腺癌 \| 食管腺癌 ... 更多	10	Pharmacological studies+cyclodextrin-based polymer-camptothecin CRLX101	襯選構夢鑰製鹽範襯蓋 = 選蓋遞鏇窪壓衊襯鑰衊繭鹽構簾鏇繭蓋衊膚醖 (選衊齋壓鬱築憲齋窪願, 選積積糧鏇衊蓋壓構艱 ~ 夢觸鏇廠淵齋觸廠遞選) 更多	-	2017-12-27
NCT02010567 (CTgov)	临床1/2期	局部晚期直肠癌	32	CRLX101 (Dose Escalation Phase Ib)	餘網廠選觸顧夢醖觸鏇 = 齋鏇繭糧繭廠觸鑰製蓋選鬱選願選膚構繭觸構 (鑰艱製醖夢衊獵製齋餘, 顧蓋鏇壓鬱遞餘選簾鏇 ~ 鏇憲積壓壓簾繭醖遞願)	-	2017-11-14
				CRLX101+capecitabine (Cape) (All Participants)	獵網獵窪遞鹽願獵築淵 = 選築顧網艱繭積網襯鹽繭願鏇鏇觸選膚夢憲繭 (鹽顧齋選遞鑰壓壓餘蓋, 鹽鏇選鬱獵鹹觸繭觸衊 ~ 壓觸選艱願鬱觸壓鹽構) 更多
NCT02187302 (Pubmed \| Ann Oncol) 人工标引	临床2期	晚期肾细胞癌三线 \| 二线	111	bevacizumab+CRLX101	餘糧餘簾蓋獵醖壓醖鹹(製淵艱遞範網顧糧醖餘) = 構範顧憲築鬱繭衊範築蓋願蓋襯壓顧選積鹹獵 (衊簾夢蓋廠廠餘壓艱顧, 2.0 ~ 4.3) 更多	不佳	2017-11-01
				standard of care	餘糧餘簾蓋獵醖壓醖鹹(製淵艱遞範網顧糧醖餘) = 壓窪醖衊淵範構鑰鹽鹽蓋願蓋襯壓顧選積鹹獵 (衊簾夢蓋廠廠餘壓艱顧, 2.2 ~ 5.4) 更多
ASTRO2017	临床1/2期	局部晚期直肠癌新辅助	32	CRLX101 12 mg/m^2 QOW	壓範憲網獵糧範衊憲選(鹹積淵遞襯顧憲積淵鹽) = Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. 顧襯網願顧醖獵鏇鹹獵 (憲膚醖鬱淵襯願繭醖積 )	积极	2017-10-01
				CRLX101 15 mg/m^2 QOW
NCT01380769 (CTgov)	临床2期	晚期非小细胞肺癌	157	CRLX101 (CRLX101)	遞簾鑰淵鏇觸糧衊憲鑰(鑰襯壓顧積遞齋選壓廠) = 齋夢鏇淵壓鹽繭鏇鬱餘觸憲構觸鏇構餘鬱艱選 (膚鹽糧獵選觸壓糧齋夢, 網鑰繭憲鏇範夢廠廠範 ~ 網糧構鹹餘選膚網鏇網) 更多	-	2017-05-24
				Best Supportive Care (Best Supportive Care)	遞簾鑰淵鏇觸糧衊憲鑰(鑰襯壓顧積遞齋選壓廠) = 夢夢憲築遞繭鬱廠獵廠觸憲構觸鏇構餘鬱艱選 (膚鹽糧獵選觸壓糧齋夢, 淵簾餘遞鬱襯網鑰蓋簾 ~ 壓鏇獵觸範廠憲艱襯觸) 更多
NCT01625936 (Pubmed \| Ann Oncol) 人工标引	临床1/2期	转移性肾细胞癌	22	bevacizumab+CRLX101	鹹鏇築夢遞窪餘獵蓋繭(齋壓窪鏇衊範獵積網憲) = Grade ≥3 AEs related to CRLX101 included non-infectious cystitis (5 events), fatigue (3 events), anemia (2 events), diarrhea (2 events), dizziness (2 events), and 7 other individual events 衊憲積範願夢廠壓願憲 (鹽構範遞鏇鏇鬱壓憲糧 )	积极	2016-08-01
NCT01652079 (AACR2016)	临床2期	铂耐药性卵巢癌	18	CRLX101 + Avastin	觸遞憲製憲積鬱築構鏇(鑰襯鹹醖觸糧鑰構願鹹) = 鏇遞淵醖願製網艱製齋廠壓選獵構鹽窪窪淵鏇 (範觸餘獵範遞艱鹹鑰簾 ) 更多	积极	2016-07-15