SYHA1813 / CSPC Pharma, Shanghai Inst. of Materia Medica - LARVOL DELTA

SYHA1813, A VEGFR and CSF1R Inhibitor, in Patients With Recurrent High-Grade Gliomas: A Multicenter, Open-Label Phase I Study. (PubMed, Ann Clin Transl Neurol) - P1 | "SYHA1813 exhibits encouraging anti-tumor activity with a manageable safety profile for the treatment of recurrent high-grade gliomas, especially glioblastoma."

Journal • P1 data • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • CSF1R

Dual targeting of VEGFR2 and CSF1R with SYHA1813 confers novel strategy for treating both BRAF wild-type and mutant melanoma. (PubMed, Cancer Cell Int) - "Dual targeting of VEGFR2 and CSF1R with SYHA1813 confers a novel microenvironmentcentric strategy for treating both BRAF wildtype and mutant melanoma. By concurrently disrupting angiogenesis and macrophagemediated immunosuppression, SYHA1813 demonstrates strong therapeutic and antimetastatic activity to melanoma, warranting further clinical development as monotherapy or in combination with BRAF V600E inhibitors."

Journal • Melanoma • Oncology • Solid Tumor • BRAF • CD31 • CSF1R • ENG • KDR • MRC1 • PECAM1

A novel compound, SYHA1813, inhibits malignant meningioma growth directly by boosting p53 pathway activation and impairing DNA repair. (PubMed, Front Oncol) - "This study unveiled a novel antitumor mechanism of SYHA1813, showing its ability to directly target and kill meningioma cells in vitro and in vivo. Our findings highlighted the promising potential of SYHA1813 as a therapeutic agent for treating malignant meningiomas."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Meningioma • Oncology • Solid Tumor

A Novel Compound, SYHA1813, Inhibits Malignant Meningioma Growth Directly by Boosting p53 Pathway Activation and Impairing DNA Repair (Front Oncol) - "Mechanistically, RNA-seq revealed that SYHA1813 activated P53 pathway and impaired DNA repair. In vivo, SYHA1813 effectively inhibited the growth of meningioma xenografts in a mouse model."

Preclinical • Meningioma

A Phase II Study of SYHA1813 for Recurrent or Progressive High-Grade Meningioma (clinicaltrials.gov) - P2 | N=56 | Not yet recruiting | Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd

New P2 trial • Brain Cancer • CNS Tumor • Meningioma • Oncology • Solid Tumor

Safety and Efficacy of SYHA1813 Single Agent or in Combination With Different Regimens in Unresectable Locally Advanced or Metastatic Solid Tumors. (clinicaltrials.gov) - P1/2 | N=380 | Not yet recruiting | Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd

New P1/2 trial • Oncology • Solid Tumor

Relative Bioavailability and Food Effect of SYHA1813 Oral Solution in Healthy Participants (clinicaltrials.gov) - P1 | N=19 | Completed | Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd | Not yet recruiting ➔ Completed

Trial completion

New hope for neuro-oncology: SYHA1813 drug research results are leading to treatment changes! [Google translation] (Sohu.com) - P1 | N=38 | ChiCTR2100045380 | "At the 2024 European Congress of Medical Oncology (ESMO) held in Barcelona, ​​Spain recently, Professor Li Wenbin, an expert in the field of neuro-oncology, brought exciting research results, focusing on the emerging innovative drug SYHA1813....The data in this study came from 38 patients with recurrent glioblastoma, of which 18.4% achieved objective remission and 52.6% achieved disease control. This result reveals the potential of SYHA1813 in blocking tumor angiogenesis and regulating the tumor microenvironment, and has a high prospect for clinical application."

P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

SYHA1813, a vascular endothelial growth factor receptor (VEGFR) 1-3/colony-stimulating factor 1 receptor (CSF1R) inhibitor, in patients with recurrent glioblastoma (ESMO 2024) - "SYHA1813 showed encouraging antitumor activity with a manageable safety profile for the treatment of recurrent glioblastoma."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CSF1R • FLT1

Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas. (PubMed, Acta Pharmacol Sin) - "Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CSF1R

Relative Bioavailability and Food Effect of SYHA1813 Oral Solution in Healthy Participants (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd

New P1 trial

Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma. (PubMed, Acta Pharm Sin B) - "SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380)."

Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CSF1R

A phase I dose-expansion cohort of SYHA1813, a vascular endothelial growth factor receptor (VEGFR) 1-3 /colony-stimulating factor 1 receptor (CSF1R) inhibitor, in patients (pts) with recurrent meningioma (ESMO 2023) - "No grade-5 TEAEs were reported. Conclusions SYHA1813 showed encouraging objective responses with a well-tolerated safety profile in pts with recurrent meningioma."

P1 data • Brain Cancer • CNS Tumor • Meningioma • Oncology • Solid Tumor • CSF1R • FLT1

A phase I dose-escalation study of SYHA1813, a VEGFR and CSF1R inhibitor, in patients with recurrent High-Grade Gliomas or Advanced Solid Tumors. (PubMed, Invest New Drugs) - "The toxicities of SYHA1813 were manageable, and encouraging antitumor efficacy was observed in patients with recurrent malignant glioma. This study is registered with the Chinese Clinical Trial Registry ( www.chictr.org.cn/index.aspx ; identifier ChiCTR2100045380)."

Journal • Metastases • P1 data • Brain Cancer • Cardiovascular • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioma • Hypertension • Mucositis • Oncology • Solid Tumor • Stomatitis • CSF1R • KDR

A multicenter, open-label, dose-escalation (DE), first-in-human study of VEGFRs and CSF1R inhibitor SYHA1813 in patients (pts) with recurrent high-grade gliomas (HGG) or advanced solid tumors (ESMO 2022) - "By multiple-dose administration, placental growth factor (PlGF), and VEGFA were significantly increased (P = .0484 and .0092, respectively), whereas soluble VEGFR2 was significantly reduced (P = .0023). Conclusions SYHA1813 showed manageable safety and encouraging antitumor activities at selected dose levels, which warranted further development in pts with recurrent HGG."

Clinical • P1 data • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Glioma • Oncology • Solid Tumor • KDR