A Phase I/II, Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib as a Single Agent in Adolescents and Adults With Recurrent, Refractory or Progressive Osteosarcoma

MP-VAC-209 is a Phase I/II, open label, single arm, multi-center study to assess safety, tolerability, and antitumor activity of vactosertib as a single agent in adolescents and adults with recurrent, refractory, or progressive osteosarcoma. Vactosertib is given orally, twice a day, to people 14 years of age and older who meet the criteria for study enrollment.

Start Date31 Mar 2023

Sponsor / Collaborator

MedPacto, Inc.

NCT06219733 / RecruitingPhase 2

A Phase II, Open-Label, Randomized, Controlled Study to Evaluate Efficacy and Safety of Vactosertib and Imatinib Combination in Patients With Advanced Desmoid Tumor (Aggressive Fibromatosis) Compared With Imatinib Monotherapy

Vactosertib and imatinib combination in patients with advanced desmoid tumor/aggressive fibromatosis (DT/AF) compared with imatinib monotherapy

Start Date23 Nov 2021

Sponsor / Collaborator

MedPacto, Inc.

NCT04064190 / Not yet recruitingPhase 2

A Phase 2 Study of TGF-β Inhibition (Vactosertib) With Anti-PD-L1 (Durvalumab) in Patients With Advanced or Recurrent Urothelial Carcinoma Failing to Achieve Response With Checkpoint Inhibition

This is Phase 2, open label, non randomized single arm study to determine whether the administration of vactosertib with durvalumab will provide meaningful increases in the Overall Response Rate (ORR) in patients with urothelial cancers that fail to achieve a response with anti-PD-1/PD-L1 based regimens

Start Date15 Oct 2021

Sponsor / Collaborator

MedPacto, Inc.

[+1]

100 Clinical Results associated with MedPacto, Inc.

0 Patents (Medical) associated with MedPacto, Inc.

Literatures (Medical) associated with MedPacto, Inc.

22 Mar 2024·Cancer Research

Abstract 728: Oral TGF-beta receptor1 inhibitor vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity

Author: Kim, Byung-Gyu ; Tomchuck, Suzanne ; Choi, Sung Hee ; Eid, Saada ; Huang, Alex Y. ; Bonner, Melissa ; Myers, Jay ; VanHeyst, Kristen ; Kingsley, Daniel ; Kim, Seong-Jin

AbstractOsteosarcoma (OS) is an aggressive malignant bone cancer, with the lung as the most frequent site of metastasis. Unresectable pulmonary metastasis remains a significant challenge with a survival rate of less than 20%. Identification of novel therapeutic strategies are desperately needed. Transforming growth factor-β1 (TGF-β) is a potent immune suppressive cytokine in OS tumor microenvironment (TME). TGF-β1 expression is increased in the sera and tumor tissues of OS patients and this increase is associated with high-grade OS and lung metastases. Therefore, blocking TGF-β1 signaling may be a novel therapy for OS treatment. In this study, we show that blocking TGF-β1 signaling using the orally bioavailable small molecule TGF-βR1 inhibitor, Vactosertib, significantly inhibited OS proliferation in vitro and in vivo. Notably, Vactosertib inhibits c-Myc expression in the OS cells and oral administration of Vactosertib significantly reduces OS growth in vivo. Vactosertib increased immune effectors (e.g., IFNγ+CD8+ cells and NK cells) and inhibited immune suppressors (e.g., M2-like TAM, MDSC) in the OS TME. Our results suggest that inhibition of TGF-β1 signaling is an effective therapeutic strategy against OS through a multi-pronged approach that targets tumor intrinsic and extrinsic factors to achieve optimal immune-effector functions and maximal clinical response.Citation Format: Sung Hee Choi, Jay Myers, Suzanne Tomchuck, Melissa Bonner, Saada Eid, Daniel Kingsley, Kristen VanHeyst, Seong-Jin Kim, Byung-Gyu Kim, Alex Y. Huang. Oral TGF-beta receptor1 inhibitor vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 728.

01 Feb 2024·Metabolism

Tm4sf19 deficiency inhibits osteoclast multinucleation and prevents bone loss

Article

Author: Park, Je Yeon ; Ooshima, Akira ; Kim, Junil ; Yoon, Kwiyeom ; Park, Seok Hee ; Yun, Rebecca ; Bae, Hyun ; Myung, Seung-Jae ; Pang, Kyoungwha ; Mizuno, Seiya ; Lee, Min Jung ; Kim, Tae-Jin ; Kang, Min Gi ; Park, Jinah ; An, Haein ; Noh, Eun Hye ; Kim, Seong-Jin ; Lee, Jihee ; Yang, Kyung-Min ; Lee, Kyung-Mi ; Letterio, John ; Park, Hyeyeon ; Kim, Minwoo ; Heo, Jin Sun ; Kim, Pyunggang ; Hong, Eunji ; Takahashi, Satoru ; Park, Sujin ; Son, Minjung

BACKGROUNDMultinucleation is a hallmark of osteoclast formation and has a unique ability to resorb bone matrix. During osteoclast differentiation, the cytoskeleton reorganization results in the generation of actin belts and eventual bone resorption. Tetraspanins are involved in adhesion, migration and fusion in various cells. However, its function in osteoclast is still unclear. In this study, we identified Tm4sf19, a member of the tetraspanin family, as a regulator of osteoclast function.MATERIALS AND METHODSWe investigate the effect of Tm4sf19 deficiency on osteoclast differentiation using bone marrow-derived macrophages obtained from wild type (WT), Tm4sf19 knockout (KO) and Tm4sf19 LELΔ mice lacking the large extracellular loop (LEL). We analyzed bone mass of young and aged WT, KO and LELΔ mice by μCT analysis. The effects of Tm4sf19 LEL-Fc fusion protein were accessed in osteoclast differentiation and osteoporosis animal model.RESULTSWe found that deficiency of Tm4sf19 inhibited osteoclast function and LEL of Tm4sf19 was responsible for its function in osteoclasts in vitro. KO and LELΔ mice exhibited higher trabecular bone mass compared to WT mice. We found that Tm4sf19 interacts with integrin αvβ3 through LEL, and that this binding is important for cytoskeletal rearrangements in osteoclast by regulating signaling downstream of integrin αvβ3. Treatment with LEL-Fc fusion protein inhibited osteoclast function in vitro and administration of LEL-Fc prevented bone loss in an osteoporosis mouse model in vivo.CONCLUSIONWe suggest that Tm4sf19 regulates osteoclast function and that LEL-Fc may be a promising drug to target bone destructive diseases caused by osteoclast hyper-differentiation.

01 Nov 2023·Molecular Oncology

Pellino 3 promotes the colitis‐associated colorectal cancer through suppression of IRF4‐mediated negative regulation of TLR4 signalling

Article

Author: Kim, Seong-Jin ; Kim, Hye-Youn ; Hong, Suntaek ; Kim, Young-Mi ; Ha Thi, Huyen Trang ; Lee, Young Jae ; Kim, Jooyoung

The incidence of colitis‐associated colorectal cancer (CAC) has increased due to a high‐nutrient diet, increased environmental stimuli and inherited gene mutations. To adequately treat CAC, drugs should be developed by identifying novel therapeutic targets. E3 ubiquitin‐protein ligase pellino homolog 3 (pellino 3; Peli3) is a RING‐type E3 ubiquitin ligase involved in inflammatory signalling; however, its role in the development and progression of CAC has not been elucidated. In this study, we studied Peli3‐deficient mice in an azoxymethane/dextran sulphate sodium‐induced CAC model. We observed that Peli3 promotes colorectal carcinogenesis with increased tumour burden and oncogenic signalling pathways. Ablation of Peli3 reduced inflammatory signalling activation at the early stage of carcinogenesis. Mechanistic studies indicate that Peli3 enhances toll‐like receptor 4 (TLR4)‐mediated inflammation through ubiquitination‐dependent degradation of interferon regulatory factor 4, a negative regulator of TLR4 in macrophages. Our study suggests an important molecular link between Peli3 and colonic inflammation‐mediated carcinogenesis. Furthermore, Peli3 can be a therapeutic target in the prevention and treatment of CAC.

News (Medical) associated with MedPacto, Inc.

28 Oct 2024

·www.prnewswire.com

Chime Biologics and Korean Listed Company MedPacto Form Strategic Partnership to Accelerate Global Biologics Development and Manufacturing

SHANGHAI, Oct. 28, 2024 /PRNewswire/ -- Chime Biologics, a leading global CDMO that enables its partners' success in biologics, today announced a strategic collaboration with MedPacto, a South Korean clinically staged company listed on KOSDAQ (235980). MedPacto, known for its focus on cancer therapeutics, will leverage Chime Biologics' expertise in biologics development to streamline the process from tech transfer to cGMP clinical manufacturing for Investigational New Drug (IND) submissions. Under the agreement, Chime Biologics will advance the Chemistry, Manufacturing, and Controls (CMC) process development for the multiple preclinical drug candidates. Dr. Jungwon Woo, President of MedPacto, stated," We are highly impressed by Chime Biologics' development and manufacture expertise, which is crucial helping us expand into major global markets. Their ability to meet international standards will greatly support our efforts to advance our assets into a new stage. This collaboration is a key step forward, and we look forward to a successful and long-term partnership." Dr. Jimmy Wei, President of Chime Biologics, added, "We are pleased to announce our strategic collaboration with MedPacto, a respected KOSDAQ-listed company with a strong portfolio of first-in-class assets. This partnership marks the beginning of a long-term relationship aimed at advancing pharmaceutical innovation. It aligns with our growth strategy in South Korea and aligns with our commitment to the region's biopharmaceutical landscape. We look forward to working closely with MedPacto and contributing to the success of their innovative pipeline." Chime Biologics is expanding its manufacturing capacity to 100,000 liters to solidify its position as a leading global CDMO. As part of this strategy, the company is actively entering the South Korean market and has signed agreements with several South Korean biotech companies to provide development and manufacturing services for antibody drugs and biosimilars. About MedPacto MedPacto (KOSDAQ: 235980) is a South Korean biomarker-driven drug discovery and development company specializing in innovative therapies for cancer. Through comprehensive pre-clinical studies and global clinical trials, MedPacto ensures the effectiveness of these treatments. By aligning its pipeline with emerging industry trends, MedPacto addresses the growing need for more effective therapies. For more information, please visit: . About Chime Biologics Chime Biologics is a global leading CDMO that has introduced the first modular biopharmaceutical plant KUBio in the world to empower its partners' success in biologics in the whole process from cell line development to commercial manufacturing. Relying on cell line development and advanced technology development from our Shanghai Innovation Center and proven success in IND-enabling through BLA filing at its Wuhan plant, Chime Biologics is providing a one-stop CMC solution for biopharmaceutical customers around the world. We share a common goal to make cutting-edge biomedicines affordable and accessible to all patients globally, fulfilling its commitment to human health. For more information, please visit: . SOURCE Chime Biologics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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Pipeline Snapshot as of 17 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Drug(Targets)	Indications	Global Highest Phase

Vactosertib ( ALK5 )	PD-L1 positive Non-Small Cell Lung Cancer More	Phase 2
MP-2021	Rheumatoid Arthritis More	Preclinical
MS-1601A	Autoimmune Diseases More	Preclinical
MPD-001	Solid tumor More	Preclinical
MA-B2	Solid tumor More	Preclinical

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