An Open-label Phase Ib Prospective Clinical Trial to Investigate Safety, Tolerability and Maximum Tolerated Dose for SCO-101 in Combination With Gemcitabine and Nab-paclitaxel in Inoperable Pancreatic Cancer Patients.

An open-label dose escalating phase Ib study of SCO-101 in combination with gemcitabine and nab-paclitaxel. The primary objectives are to establish the safety profile and the MTD of SCO-101 when combined with gemcitabine and nab-paclitaxel. The starting dose of SCO-101 is 150 mg and the dose may be increased to a maximum of 350 mg.

开始日期2020-10-27

申办/合作机构

Scandion Oncology A/S

[+1]

NCT04247256

/ Recruiting临床1/2期

An Open-label Phase II Prospective Clinical Trial to Investigate Safety, Tolerability, Maximum Tolerated Dose and Anti-tumor Effect for SCO-101 in Combination With FOLFIRI as a Safe and Efficient Treatment Modality in Metastatic or Advanced Colorectal Cancer (mCRC) Patients With Acquired FOLFIRI Resistant Cancer Disease.

This study evaluates the combination of SCO-101 to FOLFIRI for the treatment of metastatic colorectal cancer patients who have developed resistance to FOLFIRI treatment. The study is divided in two parts, where the first part evaluates the safety and toxicity of increasing doses of SCO-101 in combination with FOLFIRI at the same dose as the patient has previously developed resistance to. The second part of the study evaluates the safety and efficacy of the combination of FOLFIRI and SCO-101 at the dose level established in the first part.

开始日期2020-05-14

申办/合作机构

Scandion Oncology A/S

[+1]

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项与 Endovion 相关的文献（医药）

2025-04-01·INVESTIGATIONAL NEW DRUGS

PANTAX: a phase Ib clinical trial of the efflux pump inhibitor SCO-101 in combination with gemcitabine and nab-paclitaxel in non-resectable or metastatic pancreatic cancer

Article

作者: Kraeft, Anna-Lena ; Christensen, Signe ; Kestler, Angelika ; Reinacher-Schick, Anke ; Stenvang, Jan ; Tarpgaard, Line Schmidt ; Ladekarl, Morten ; Per Pfeiffer ; Roest, Nicklas Lindland ; Ettrich, Thomas Jens ; Nawabi, Mubeen ; Damstrup, Lars ; Vestlev, Peter Michael ; Jandu, Haatisha ; Brünner, Nils ; Shim, Susy

Summary:

De novo or acquired resistance to chemotherapy is ubiquitous in pancreatic ductal adenocarcinoma (PDAC). SCO-101 is an oral compound that may counteract chemo-resistance by interacting with SRPK1, ABCG2 drug transporter, and liver enzyme UGT1A1. We first conducted preclinical experiments in paclitaxel-resistant PDAC cells to access the tumoricidal effects of SCO-101 or SRPK1-inhibitor alone or in combination with paclitaxel. Second, we enrolled 22 patients with non-resectable PDAC in a phase Ib trial to investigate safety and pharmaco-kinetics, and to establish maximum tolerated dose (MTD) by evaluation of dose-limiting toxicities (DLTs) during the first cycle of 80% dose gemcitabine (Gem) and nab-paclitaxel (Nab) together with increasing doses of SCO-101. In paclitaxel-resistant PDAC cells in vitro, a synergistic effect between SCO-101 and paclitaxel was demonstrated. In patients, daily doses for 6 days of SCO-101 resulted in a two- to threefold drug accumulation, and drug exposure was dose proportional. Treatment was well tolerated. Transiently increased blood bilirubin attributable to SCO-101 was observed in 12 cases (55%) and associated with jaundice in three patients. One and two DLTs, respectively, were observed at 150 and 250mg dosing-levels of SCO-101, and the MTD was determined to be 200 mg of SCO-101 daily for 6 days on a bi-weekly schedule together with 80% dose of Gem and Nab. Median progression-free and overall survival was 3.3 and 9.5 months, respectively. In PDAC, SCO-101 can be added to Gem and Nab with little and manageable toxicity. However, no clear added efficacy signal was observed of the combination. Trial registration number: NCT04652205 (Nov 29, 2020).

2024-12-02·ChemMedChem

Developing Allosteric Inhibitors of SARS‐CoV‐2 RNA‐Dependent RNA Polymerase

Article

作者: Spiwok, Vojtěch ; Dostálková, Alžběta ; Danda, Matěj ; Klimešová, Anna ; Ruml, Tomáš ; Kapisheva, Marina ; Rumlová, Michaela ; Weber, Jan ; Chayka, Artem ; Janeba, Zlatko ; Zgarbová, Michala

Abstract:

The use of Fpocket and virtual screening techniques enabled us to identify potential allosteric druggable pockets within the SARS‐CoV‐2 RNA‐dependent RNA polymerase (RdRp). Of the compounds screened, compound 1 was identified as a promising inhibitor, lowering a SARS‐CoV‐2 RdRp activity to 57 % in an enzymatic assay at 10 μM concentration. The structure of compound 1 was subsequently optimized in order to preserve or enhance inhibitory activity. This involved the substitution of problematic ester and aromatic nitro groups with more inert functionalities. The N,N’‐diphenylurea scaffold with two NH groups was identified as essential for the compound's activity but also exhibited high toxicity in Calu‐3 cells. To address this issue, a scaffold hopping approach was employed to replace the urea core with potentially less toxic urea isosteres. This approach yielded several structural analogues with notable activity, specifically 2,2’‐bisimidazol (in compound 55 with residual activity RA=42 %) and (1H‐imidazol‐2‐yl)urea (in compounds 59 and 60, with RA=50 and 28 %, respectively). Despite these advances, toxicity remained a major concern. These compounds represent a promising starting point for further structure‐activity relationship studies of allosteric inhibitors of SARS‐CoV‐2 RdRp, with the goal of reducing their cytotoxicity and improving aqueous solubility.

2023-12-31·Virulence

LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells

Article

作者: Sun, Ju ; Wang, Huan ; Gu, Jiayun ; Xu, Xiaojuan ; Wang, Zhichao ; Lin, Yan ; Cao, Qi ; Xu, Yindi ; Wen, Siting ; Mao, Weiting ; Cai, Xuwang

Glaesserella parasuis is an early colonizer of the swine upper respiratory tract and can break through the respiratory barrier for further invasion. However, the mechanisms underlying G. parasuis increases epithelial barrier permeability remain unclear. This study demonstrates that G. parasuis cytolethal distending toxin (CDT) induces p53-dependent apoptosis in new-born piglet tracheal (NPTr) cells. Moreover, we report for the first time that leucine-rich repeat-containing protein 8A (LRRC8A), an essential subunit of the volume-regulated anion channel (VRAC), involves in apoptosis of NPTr cells mediated by G. parasuis CDT. Pharmacological inhibition of VRAC with either PPQ-102 or NS3728 largely attenuated CDT-induced apoptosis in NPTr cells. Additionally, experiments with cells knocked down for LRRC8A using small interfering ribonucleic acid (siRNA) or knocked out LRRC8A using CRISPR/Cas9 technology showed a significant reduction in CDT-induced apoptosis. Conversely, re-expression of Sus scrofa LRRC8A in LRRC8A^-/- NPTr cells efficiently complemented the CDT-induced apoptosis. In summary, these findings suggest that LRRC8A is pivotal for G. parasuis CDT-induced apoptosis, providing novel insights into the mechanism of apoptosis caused by CDT.

项与 Endovion 相关的新闻（医药）

2024-08-29

·scandiononcology.com

Scandion Oncology – Interim Report Q2 2024

Scandion Oncology (Scandion) today announces its Interim Report Q2 2024. The following is taken from the report. Francois Martelet, CEO: “With positive data and new financing, our top priority is now business development and partnering activities” Key Figures & Highlights Highlights during Q2 2024 On April 19, Scandion Oncology announced the intention, subject to authorizations by the annual general meeting of the Company on 6 May 2024, to carry out a Rights Issue with preferential rights for the Company’s existing shareholders. The Rights Issue of potentially SEK 60 million is secured up to SEK 30.6 million. On May 13, Scandion announced final data from the Phase Ib open-label PANTAX trial which confirms the good safety profile of SCO-101 and shows good signs of efficacy in hard-to-treat pancreatic cancer. On June 3, Scandion announced, that the company has entered into an agreement with Vator Securities AB regarding the service as a Certified Adviser. Vator Securities will be appointed Certified Adviser (CA) on September 1, 2024. On June 25, Scandion announced the outcome of the rights issue of units. The Rights Issue was subscribed to a total of approximately 50.3 percent. Through the Rights Issue, Scandion will initially receive approximately SEK 30.6 million before issue costs and in the event of exercise of warrants of series TO 2 and TO 3, in November 2024 and April 2025, respectively, the Company will receive additional proceeds. Highlights after the end of the period On July 1, Scandion board member Michel Ducreux stepped down due to ESMO scientific society’s guidelines prohibiting such board positions. He joined the advisory board. On August 16, Scandion Oncology achieved Maximum Tolerated Dose (MTD) for CORIST part 3. The established MTD for a 4-Days schedule of SCO-101 in combination with FOLFIRI was found to be 250 mg daily SCO-101, 50% irinotecan and 100% Leucovorin and 5-FU. On August 19, Scandion announced that the top priority following the very encouraging part 3 CORIST data is business development and partnering activities. As part of these efforts, Scandion is working together with Back Bay Life Science Advisors LLC, a prominent life sciences investment banking firm, to explore and evaluate actionable strategic and financial alternatives. The Interim Report Q2 2024 is available on the Company's website: www.scandiononcology.com. Audiocast today, August 29 at 11:00 am CET Today at 11:00, Scandion Oncology’s executive management will host a webcast and conference call presenting the results and a company update. At the end of the presentation there will be a Q&A session. Access to the event can be obtained as follows: LIVE access today Thursday, August 29, 2024, at 11:00 CET: https://financialhearings.com/event/48942 REPLAY access Webcast replay will be available at www.scandiononcology.com in the Investors section and at www.financialhearings.com For further information please contact: Johnny Stilou, CFO Phone: +45 2960 3532 E-mail: jos@scandiononcology.com The information was provided by the contact person above for publication on August 29, 2024, at 07.00 CET. About Scandion Oncology Scandion Oncology (Scandion) is a clinical-stage biotech company using an innovative drug efflux pump inhibition technique with biomodulation capabilities on ABCG2 and UGT1A1 targets to revert drug resistance. Drug resistance remains a massive problem in cancer treatment and in the development of new medicines. Scandion’s lead compound SCO-101 is currently studying metastatic colorectal cancer (mCRC) in its Phase 2 CORIST trial, while the PANTAX Phase 1 program is developing SCO-101 for pancreatic cancer. Scandion is based in Copenhagen and is listed on Nasdaq First North Growth Market Sweden (ticker: SCOL). Västra Hamnen Corporate Finance is the Company's certified advisor on Nasdaq First North Growth Market.

临床1期临床2期高管变更

2024-08-19

·scandiononcology.com

Scandion Oncology strengthens partnering outreach

Scandion Oncology (Scandion), an innovative drug efflux pump inhibition company using biomodulation capabilities to revert drug resistance, today announced that the top priority following the very encouraging part 3 CORIST data is business development and partnering activities. As part of these efforts, Scandion is working together with Back Bay Life Science Advisors LLC, a prominent life sciences investment banking firm, to explore and evaluate actionable strategic and financial alternatives. This decision reflects the company’s commitment to both the ongoing development of SCO-101 and maximizing shareholder value. Strategic alternatives include partnerships, divesting certain assets, and exploring a potential sale of the company. “The clinical data generated by Scandion’s SCO-101 throughout CORIST 1 to 3 certainly demonstrate the potential of the molecule to significantly reduce chemotherapy drug resistance due to its unique mechanism of action,” said Francois Martelet, CEO of Scandion Oncology. “While focusing on business development and partnering activities we will work with our clinical advisors on the best step forward to ensure SCO-101 reaches its potential in the light of current standard of care.” For further information please contact: Johnny Stilou, CFO Phone: +45 2960 3532 E-mail: jos@scandiononcology.com The information was provided by the contact person above for publication on August 19, 2024, at 07.00 CET. About Scandion Oncology Scandion Oncology (Scandion) is a clinical-stage biotech company using an innovative drug efflux pump inhibition technique with biomodulation capabilities on ABCG2 and UGT1A1 targets to revert drug resistance. Drug resistance remains a massive problem in cancer treatment and in the development of new medicines. Scandion’s lead compound SCO-101 is currently studying metastatic colorectal cancer (mCRC) in its Phase 2 CORIST trial, while the PANTAX Phase 1 program is developing SCO-101 for pancreatic cancer. Scandion is based in Copenhagen and is listed on Nasdaq First North Growth Market Sweden (ticker: SCOL). Västra Hamnen Corporate Finance is the Company's certified advisor on Nasdaq First North Growth Market.

临床2期临床1期

2024-08-16

·scandiononcology

Scandion Oncology achieves Maximum Tolerated Dose for CORIST part 3

Scandion Oncology (Scandion), an innovative drug efflux pump inhibition company using biomodulation capabilities to revert drug resistance, today announced topline data for the CORIST part 3 continuation trial and that the company established the maximum tolerated dose (MTD) of SCO-101 in combination with the chemotherapy FOLFIRI in colorectal cancer patients. The established MTD for a 4-Days schedule of SCO-101 in combination with FOLFIRI was found to be 250 mg daily SCO-101, 50% irinotecan and 100% Leucovorin and 5-FU. “We are pleased to have reached the primary endpoint of this continuation trial, establishing the MTD of SCO-101 in combination with FOLFIRI,” said Lars Damstrup, CMO of Scandion Oncology. “We now have the recommended dose that we may use in the next steps of the development of SCO-101.” The continuation study of CORIST part 3 included 3 patients. The dose of SCO-101 was the same as in the previous cohort, i.e., 250 mg per day for four days. Folinic acid and 5-FU were administered as per standard of care. The dose of irinotecan was increased from 50% to 65% of the normal standard dose. Of the 3 patients, 2 experienced a dose-limiting toxicity of neutropenia, which was expected based on previous data. No new safety signals were detected. Final data in the CORIST part 3 continuation trial is expected in the first half of 2025. For further information please contact: Johnny Stilou, CFO Phone: +45 2960 3532 E-mail: jos@scandiononcology.com This information is information that Scandion Oncology A/S is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above on August 16, 2024, at 07.00 CET. About Scandion Oncology Scandion Oncology (Scandion) is a clinical-stage biotech company using an innovative drug efflux pump inhibition technique with biomodulation capabilities on ABCG2 and UGT1A1 targets to revert drug resistance. Drug resistance remains a massive problem in cancer treatment and in the development of new medicines. Scandion’s lead compound SCO-101 is currently studying metastatic colorectal cancer (mCRC) in its Phase 2 CORIST trial, while the PANTAX Phase 1 program is developing SCO-101 for pancreatic cancer. Scandion is based in Copenhagen and is listed on Nasdaq First North Growth Market Sweden (ticker: SCOL). Västra Hamnen Corporate Finance is the Company's certified advisor on Nasdaq First North Growth Market. This information is information that Scandion Oncology is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact persons set out above, at 2024-08-16 07:00 CEST.

临床结果临床1期临床2期

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05835

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
局部晚期胰腺腺癌	临床2期	丹麦	Scandion Oncology A/S	2020-10-27
局部晚期胰腺腺癌	临床2期	德国	Scandion Oncology A/S	2020-10-27
转移性胰腺腺癌	临床2期	丹麦	Scandion Oncology A/S	2020-10-27
转移性胰腺腺癌	临床2期	德国	Scandion Oncology A/S	2020-10-27
胰腺癌	临床2期	丹麦	Scandion Oncology A/S	2020-10-27
不能切除性胰腺癌	临床2期	丹麦	Scandion Oncology A/S	2020-10-27
不能切除性胰腺癌	临床2期	德国	Scandion Oncology A/S	2020-10-27
转移性结直肠癌	临床2期	德国	Scandion Oncology A/S	2020-05-14
转移性结直肠癌	临床2期	西班牙	Scandion Oncology A/S	2020-05-14
乳腺癌	临床1期	丹麦	Scandion Oncology A/S	2019-06-27

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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


NCT04652206 (ESMO 12023 \| ESMO 22023) 人工标引	临床1期	胰腺癌	22	SCO-101+gemcitabine + nab-paclitaxel	衊襯淵鹹廠廠製淵鏇願(蓋憲繭範鏇鏇簾簾構蓋) = 齋膚顧獵鹹鬱鏇鹹繭製觸齋鏇網積鹽糧廠廠廠 (鬱遞齋艱襯顧選構繭選 )	积极	2023-10-23
				SCO-101+gemcitabine + nab-paclitaxel	襯襯網襯製襯窪夢餘憲(顧鏇蓋願鏇憲繭顧顧糧) = 糧壓鹹廠膚構餘窪淵鏇築築選選齋壓衊製選鏇 (淵襯簾夢獵鹹簾鹹襯鹽 )