The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid tumors. An investigational drug is one that has not been approved by the U.S. Food & Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat.
The goals of this part of the study are:
* Establish a recommended dose of silmitasertib in combination with chemotherapy
* Test the safety and tolerability of silmitasertib in combination with chemotherapy in subjects with cancer
* To determine the activity of study treatments chosen based on:
* How each subject responds to the study treatment
* How long a subject lives without their disease returning/progressing

Start Date30 Oct 2024

Sponsor / Collaborator

Hershey Medical Center

NCT06202521

/ RecruitingPhase 2

Evaluation of the Safety and Efficacy of Silmitasertib (CX-4945) in Combination With Standard of Care (SOC) for Treating Patients With Community-Acquired Pneumonia (CAP) Associated With SARS-CoV-2 and Influenza Viral Infections

This is a Phase II, multi-center, double-blind, randomized, interventional study in approximately 120 subjects to evaluate clinical benefit of CX-4945 in adult outpatients with SARS-CoV-2 and influenza viral infection-associated pneumonia. The subjects will be recruited into two domains, including SARS-CoV-2 and influenza virus domains. The study will compare the efficacy of Standard of Care (SOC) combined with CX-4945 against SOC paired with a placebo, utilizing a 1:1 allocation ratio in each domain.

Start Date27 Feb 2024

Sponsor / Collaborator

Senhwa Biosciences, Inc.

NCT05817708

/ CompletedPhase 1

A Dose Selection Phase 1 Study Evaluating the Safety and Tolerability of Silmitasertib

This is a Phase I single center, open-label, parallel design in 30 subjects to evaluate safety and tolerability of CX-4945 200mg QD, 200 mg BID and 400mg BID doses (10 subjects in each regimen) for continuously 5 days in healthy subjects for dose selection.

Start Date28 Nov 2022

Sponsor / Collaborator

Senhwa Biosciences, Inc.

100 Clinical Results associated with Silmitasertib

100 Translational Medicine associated with Silmitasertib

100 Patents (Medical) associated with Silmitasertib

362

Literatures (Medical) associated with Silmitasertib

31 Dec 2025·CANCER BIOLOGY & THERAPY

Targeting the IKZF1/BCL-2 axis as a novel therapeutic strategy for treating acute T-cell lymphoblastic leukemia

Article

Author: Li, Jun ; Ye, Chunmei ; Li, Hui ; Li, Juan

OBJECTIVES:

Acute T-cell lymphoblastic leukemia (T-ALL) is a severe hematologic malignancy with limited treatment options and poor long-term survival. This study explores the role of IKZF1 in regulating BCL-2 expression in T-ALL.

METHODS:

CUT&Tag and CUT&Run assays were employed to assess IKZF1 binding to the BCL-2 promoter. IKZF1 overexpression and knockdown experiments were performed in T-ALL cell lines. The effects of CX-4945 and venetoclax, alone and in combination, were evaluated in vitro and in vivo T-ALL models.

RESULTS:

CUT&Tag sequencing identified IKZF1 binding to the BCL-2 promoter, establishing it as a transcriptional repressor. Functional assays demonstrated that IKZF1 overexpression reduced BCL-2 mRNA levels and increased repressive histone marks at the BCL-2 promoter, while IKZF1 knockdown led to elevated BCL-2 expression. CX-4945, a CK2 inhibitor, could reduced BCL-2 levels in T-ALL cells. Notably, knockdown of IKZF1 partially rescued the CX-4945-induced repression of BCL-2. These results underscore the CK2-IKZF1 signaling axis as a key regulator of BCL-2 expression. In vitro, CX-4945 enhanced the cytotoxicity of venetoclax, with the combination showing significant synergistic effects and increased apoptosis in T-ALL cell lines. In vivo studies with cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models demonstrated that CX-4945 and venetoclax combined therapy provided superior therapeutic efficacy, reducing tumor burden and prolonging survival compared to single-agent treatments.

CONCLUSIONS:

IKZF1 represses BCL-2 in T-ALL, and targeting the CK2-IKZF1 axis with CX-4945 and venetoclax offers a promising therapeutic strategy, showing enhanced efficacy and potential as a novel treatment approach for T-ALL.

01 May 2025·ANTIVIRAL RESEARCH

Assessment of repurposed compounds against coronaviruses highlights the antiviral broad-spectrum activity of host-targeting iminosugars and confirms the activity of potent directly acting antivirals

Article

Author: Hill, Michelle L ; Gileadi, Carina ; Brun, Juliane ; Kiappes, J L ; Witt, Karolina D ; Dwek, Raymond A ; von Delft, Annette ; Rangel, Victor ; Arman, Benediktus Yohan ; Makower, Laetitia L ; Zitzmann, Nicole ; Alonzi, Dominic S

The COVID-19 pandemic highlights the need for novel antiviral drug discovery approaches that could dramatically shorten timelines from compound discovery to clinical development. At the beginning of the pandemic, repurposing approaches were at the forefront of early research efforts to screen for antiviral activity against SARS-CoV-2 in over 2500 compounds. Here, we report cellular screening results of 100 FDA-approved and experimental compounds against SARS-CoV-2 in the human Calu-3 cell line. We observed 13 compounds showing antiviral activity against SARS-CoV-2, including seven FDA-approved compounds (remdesivir, boceprevir, amiloride, nafamostat, cisplatin, silmitasertib, and miglustat), and six compounds in pre-clinical and clinical development (tarloxotinib, lucerastat (NB-DGJ), MON-DNJ, NAP-DNJ, NN-DGJ and NN-DNJ). Further, we observed that our screening hits include several host-targeting antivirals, namely iminosugars, that are largely non-toxic and offer a large therapeutic window. The most-developed iminosugar MON-DNJ (UV-4B), which has been evaluated in a Phase 1 clinical trial, shows antiviral activity against SARS-CoV-2 wild type as well as alpha, beta, gamma, delta, and Omicron variants. Its activity also extended to another betacoronavirus HCoV OC43, but not alphacoronavirus HCoV 229E. Our cellular screening results add to the body of knowledge on antivirals against coronaviruses and confirm the antiviral efficacy of iminosugars in cellular assays using the human lung-cell line Calu-3.

01 Feb 2025·iScience

Single-cell and spatial transcriptomics reveal pre-metastatic subsets and therapeutic targets in penile carcinoma

Article

Author: Xu, Da-Ming ; Mo, Miao ; Han, Hui ; Chen, Ling-Xiao

Tumor heterogeneity, driven by branching evolution and genomic mutations, complicates cancer treatment. Understanding malignant cell evolution across various tumors aids in identifying pre-metastatic subpopulations for optimized therapies. Using bulk RNA sequencing (6 primary penile carcinomas, 6 metastatic lymph nodes, GSE196978), single-cell RNA sequencing (4 advanced penile carcinomas), spatial transcriptomics (Squamous cell carcinoma [SCC]: GSE144239-GSM4565823 and SCC: GSE144239-GSM4565826), and cell assays with Silmitasertib, we mapped heterogeneity and pinpointed therapeutic targets. In penile carcinoma, we discovered an MMP3+SPP1+ pre-metastatic subset and casein kinase 2 alpha 1 (CK2α) overexpression. The nuclear factor κB (NF-κB) pathway may drive metastasis. Pan-cancer analysis showed that MMP3 and SPP1 link to epithelial mesenchymal transition (EMT) and drug resistance, while CK2α activates oncogenes. Silmitasertib, a CK2α inhibitor, exhibited anti-tumor effects in penile carcinoma cells. Validated across 98 single-cell and 6 spatial datasets, our study advances the understanding of tumorigenesis and metastasis, highlighting Silmitasertib as a potential therapeutic agent.

News (Medical) associated with Silmitasertib

07 Nov 2024

·www.outsourcing-pharma.com

Senhwa Biosciences starts trial of silmitasertib in children with difficult to treat cancers

Silmitasertib, also known as CX-4945, was originally developed by Cylene Pharmaceuticals, a San Diego-based biotech that ceased operations in 2013. Since then, Senhwa Biosciences, which is headquartered in Taiwan but also has a San Diego base gained the rights to the small molecule, first in class, casein kinase 2 (CK2) inhibitor. CK2 is overexpressed in a number of tumors. Various studies have shown silmitasertib appears to have good anticancer activity. For example , it triggers autophagy and promote apoptosis of cancer cells in pancreatic and lung cancer and also promotes colorectal cancer cell death. Senhwa is currently testing silmitasertib in early human trials for treatment of cholangiocarcinoma, basal cell carcinoma, medulloblastoma and neuroblastoma. In preclinical studies , the small molecule showed good oral bioavailability and was able to effectively inhibit tumor growth in animal studies while being well tolerated. When combined with DNA-damaging chemotherapy drugs such as gemcitabine and cisplatin, the anticancer activity of silmitasertib seems to be enhanced so it is being tested as an add-on therapy in the new trial. The phase 1/2 study will include 114 children and young adults with relapsed or refractory neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma in the US. "We are thrilled to be able to move this important research forward on a larger scale," said Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium, which is supporting the study. googletag.cmd.push(function () { googletag.display('text-ad1'); }); “The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally.” Additional indication for Covid-19 patients As well as being a promising anti-cancer therapy, silmitasertib is being tested to treat people infected with SARS-CoV-2 who develop serious symptoms that require hospitalization in a phase 2 study. CK2 is involved in regulating signaling pathways important for innate immune responses. Inhibiting this protein kinase can help reduce the excessive cytokine storm immune response often seen in people with severe Covid-19. Studies have shown that silmitasertib and other kinase inhibitors seem to reduce levels of inflammatory biomarkers such as interleukin 6 and tumor necrosis factor-alpha, both of which are high in hospitalized Covid-19 patients. So far results phase 2 results announced by Senhwa have been good with significantly better recovery times observed for Covid-19 patients given silmitasertib versus standard care, with a good safety profile.

Phase 2Clinical ResultPhase 1

06 Nov 2024

·www.prnewswire.com

Senhwa Biosciences announces first patient dosed in the Phase I/II study of Silmitasertib in children and young adults with relapsed refractory solid tumors.

TAIPEI and SAN DIEGO, Nov. 6, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that the enrollment of the first patient at Penn State Health Children's Hospital in its Phase I/II clinical study evaluating the efficacy of Silmitasertib (CX-4945) in combination with chemotherapy for children and young adults with relapsed or refractory solid tumors. This innovative trial seeks to establish a recommended dose of Silmitasertib in combination with chemotherapy and assess the safety, tolerability and efficacy in patients with cancer, with a focus on neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma. "This clinical trial is a critical piece in understanding the mechanism of how the medicine works and develop more precise treatments for our patients," said Dr. Chandrika Behura, study chair and principal investigator, Four Diamonds researcher and associate professor of pediatrics at the College of Medicine. "It's very important to develop the right combination that can be the most toxic to cancer cells, but the least harmful to the normal cells around them." The study is projected to enroll up to 114 participants nationwide through the Beat Childhood Cancer Research Consortium member hospitals. By evaluating the activity of the study treatments based on individual responses and duration of disease control, the trial aims to develop novel therapeutic approaches. "We are thrilled to be able to move this important research forward on a larger scale," said Dr. Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium. "The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally." With the College of Medicine serving as its home, the Beat Childhood Cancer Research Consortium is a worldwide network of more than 50 universities and children's hospitals focused on saving lives and helping the Children's Hospital make a lasting difference around the world. Funding for this clinical trial is provided by the Beat Childhood Cancer Foundation and the Little Warrior Foundation. Funding for Behura's research which led to the clinical trial was provided by Four Diamonds. "This is the culmination of the work of many people over the years," said Suzanne Graney, executive director of Four Diamonds. "Without the dedication of our physician-scientists and the generosity of our donors and community, this kind of essential work to improve treatments with an ultimate goal of curing cancer would not be possible." The pediatric cancer care specialists at Beat Childhood Cancer Research Consortium hospitals and researchers at the College of Medicine are dedicated to turning groundbreaking discoveries into lifesaving treatments for childhood cancer. "By expanding our research and increasing clinical trials, we are exploring immunotherapy, cellular therapy and precision medicine to deliver the most optimized care to each unique patient," said Dr. Dr. Yatin Vyas, pediatrician-in-chief and chair of the Department of Pediatrics at the Children's Hospital. "We are greatly honored to collaborate with the Penn State College of Medicine and Beat Childhood Cancer Research Consortium, which have been diligently fighting childhood cancers by infusing invaluable resources from over 50 universities and children's hospitals across the United States for the clinical study," said Jin-Ding Huang, PhD, CEO of Senhwa Biosciences, Inc. "We appreciate for having the opportunity of providing Silmitasertib as a potential effective treatment and look forward to realizing its therapeutic value in this urgently needed field for childhood cancers though this study". SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical StudyImmunotherapy

13 Sep 2024

·www.prnewswire.com

US FDA Grants RPD Designation to Senhwa Biosciences Silmitasertib for Pediatric Neuroblastoma

TAIPEI and SAN DIEGO, Sept. 13, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that its new drug Silmitasertib (CX-4945) was granted a rare pediatric disease designation (RPDD) by US FDA for the treatment of neuroblastoma. This is the recognition obtained again after Silmitasertib (CX-4945) received RPDD in medulloblastoma from the FDA in July 2020, demonstrating the great potential of Silmitasertib (CX-4945) in the development of treatments for rare pediatric cancers. Silmitasertib is a first-in-class small molecule drug that targets the CK2 protein and acts as a CK2 inhibitor that exhibited antitumor activity in pre-clinical study of neuroblastoma. The RPD designation will qualify the drug for the priority review voucher (PRV) program meant to encourage development of novel therapies for rare pediatric diseases. Silmitasetib has previously granted 1 RPD and 3 orphan drug designations (ODD) by the FDA. "The RPD designation offers sponsors the additional incentive by requesting priority review vouchers (PRVs) for their future marketing applications, and this approach encourages the drug development for the treatment of rare pediatric diseases," said Jin-Ding Huang, PhD, CEO of Senhwa Biosciences, Inc. Neuroblastoma, an embryonic tumor of the peripheral sympathetic nervous system, is the third most common pediatric cancer and the most common cancer in infants. It is mostly diagnosed in infancy at an average of 1 to 2 years old. There are an estimated 700 to 800 new cases of neuroblastoma each year in the United States. While low and intermediate-risk neuroblastoma have a very high rate of survival, high-risk neuroblastoma has a 5-year survival rate of about 50%, and it has a high likelihood of recurrence even with intense multimodal treatments. There is currently no standard treatment for patients with relapsed/refractory neuroblastoma. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Orphan DrugPriority ReviewBreakthrough Therapy

100 Deals associated with Silmitasertib

External Link

KEGG	Wiki	ATC	Drug Bank
-	Silmitasertib	-	DB15408

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ewing Sarcoma	Phase 2	US	Senhwa Biosciences, Inc.	06 Nov 2024
Liposarcoma	Phase 2	US	Senhwa Biosciences, Inc.	06 Nov 2024
Rhabdomyosarcoma	Phase 2	US	Senhwa Biosciences, Inc.	06 Nov 2024
Influenza, Human	Phase 2	TW	Senhwa Biosciences, Inc.	27 Feb 2024
Community Acquired Pneumonia	Phase 2	TW	Senhwa Biosciences, Inc.	27 Feb 2024
COVID-19	Phase 2	US	Senhwa Biosciences, Inc.	30 Nov 2020
Bile Duct Neoplasms	Phase 2	US	Senhwa Biosciences, Inc.	-
Bile Duct Neoplasms	Phase 2	KR	Senhwa Biosciences, Inc.	-
Bile Duct Neoplasms	Phase 2	TW	Senhwa Biosciences, Inc.	-
Neuroblastoma	Phase 2	US	Senhwa Biosciences, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05817708 (CTgov)	Phase 1	COVID-19	30	CX-4945 (CX-4945 200mg QD)	qkrlwezazz(jedlrztbzj) = kuurdpfygr kztgwvnynv (xzfpuwzhmf, sujghmcrvd - udrhppljjg) View more	-	27 Jan 2025
				CX-4945 (CX-4945 200mg BID)	qkrlwezazz(jedlrztbzj) = qnxtvcwzxt kztgwvnynv (xzfpuwzhmf, jklugyotdy - oobgbqvjzt) View more
NCT04663737 (CTgov)	Phase 2	COVID-19	20	Silmitasertib (Group A)	dspvigeevl(hihaxhyctc) = camphdvhxc qqichmqmqa (hemodemuco, hgusfrzhet - ypirqvxaaa) View more	-	16 Dec 2024
				SOC (Group B)	dspvigeevl(hihaxhyctc) = bmavzqywty qqichmqmqa (hemodemuco, lehqtfxyqs - yqofdhbxhj) View more
NCT02128282 (S4-13-001, Pubmed) Manual	Phase 1/2	Bile Duct Neoplasms First line	84	Gemcitabine+Cisplatin+Silmitasertib	jriembnosc(ebumojjuuu) = ikktdrymop psqmpzkxkm (kvzwbmqdek, 7.6 - 14.7) View more	Positive	24 Sep 2022
				Gemcitabine+Cisplatin	jriembnosc(ebumojjuuu) = dzogaozbpl psqmpzkxkm (kvzwbmqdek, 3.1 - NE) View more
NCT04663737 (Biospace) Manual	Phase 2	COVID-19	20	CX-4945	dolduqhpoq(nrmaxouqxg) = vahaltcxax fjsrrbhdqy (pvwwddzqki ) View more	Positive	20 Oct 2021
				Standard of Care	gytstlpfva(htfyggqvko) = kivridmsnn mbhatyxhfo (ppmswhtyol ) View more
NCT02128282 (S4-13-001, ASCO_GI 12021 \| ASCO_GI 22021) Manual	Phase 1/2	Metastatic Cholangiocarcinoma First line	87	gemcitabine+cisplatin+Silmitasertib	thrplwfwka(rsxkodydpp) = nrjtwfldwh swedobgvek (flfadypcgu, 7.6 - 14.7) View more	Positive	22 Jan 2021
OR02-2 (ENDO2019)	Not Applicable	Adrenocortical Carcinoma NR5A1	-	CX-4945	ushmxyzqzd(xsgiezceoz) = lswwimgbjk ugdezcckjn (izefrgjdue )	Positive	30 Apr 2019
NCT02128282 (ASCO_GI2017)	Phase 1/2	Advanced biliary tract cancer	127	CX-4945	zeebvrwaaz(fxrsswvjqt) = ncycdvrriz pjkgqkqjqp (pljrjuqczc ) View more	-	21 Mar 2017

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