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Silmitasertib - Senhwa Biosciences

Drug Profile

Silmitasertib - Senhwa Biosciences

Alternative Names: CX 4945

Latest Information Update: 25 Mar 2024

At a glance

  • Originator Cylene Pharmaceuticals
  • Developer Cylene Pharmaceuticals; Penn State College of Medicine; Senhwa Biosciences; Stanford University School of Medicine
  • Class 3-ring heterocyclic compounds; Antineoplastics; Antivirals; Carboxylic acids; Naphthyridines; Small molecules
  • Mechanism of Action Casein kinase II inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    Yes - Cholangiocarcinoma; Biliary cancer; Medulloblastoma
  • New Molecular Entity Yes

Highest Development Phases

  • Phase II Community-acquired pneumonia; COVID 2019 infections
  • Phase I/II Cholangiocarcinoma; Medulloblastoma
  • Phase I Basal cell cancer
  • Preclinical Acute myeloid leukaemia; Precursor B-cell lymphoblastic leukaemia-lymphoma; Precursor T-cell lymphoblastic leukaemia-lymphoma
  • No development reported Giant lymph node hyperplasia; Multiple myeloma; Solid tumours

Most Recent Events

  • 20 Mar 2024 Phase-II clinical trials in Community-acquired pneumonia (Combination therapy) in Taiwan (PO) (NCT06202521)
  • 08 Mar 2024 Pediatric Brain Tumor Consortium suspends phase I/II clinical trial in Medulloblastoma (Second-line therapy or greater, Recurrent, In adolescents, In adults, In children, In the elderly) in USA (PO) due to drug supply issues(NCT03904862)
  • 26 Dec 2023 Taiwan FDA approves IND application for Silmitasertib in Community-acquired pneumonia

Development Overview

Introduction

Silmitasertib (CX 4945) is an orally-administered, small molecule, inhibitor of casein kinase II (CK2), being developed by Senhwa Biosciences, for the treatment of COVID-2019 infections, community-acquired pneumonia, cholangiocarcinoma, acute myeloid leukemia and solid tumours, including Castleman's disease (giant lymph node hyperplasia), multiple myeloma. The compound was originally developed by Cylene Pharmaceuticals. CK2 plays a direct role in DNA damage repair and has elevated activity in cancer cells which enables tumour to survive damage induced by chemotherapeutic agents. Silmitasertib inhibits CK2 resulting in inhibition of DNA repair by modulating expected pathways without affecting normal cells. Inhibition of CK2 by Silmitasertib diminishes the secretion of IL-6 and MCP-1. Silmitasertib treatment also reduces the expression of TNF-a and CCL4 in NiSO4-stimulated MoDCs. Clinical development is underway in various countries. Preclinical development for precursor B-cell lymphoblastic leukaemia lymphoma is underway in Taiwan and for acute myeloid leukemia is underway in the US. Preclinical development for T-cell acute lymphoblastic leukemia is underway in China.

Silmitasertib is being developed as a therapeutic for COVID-2019 infections. Research revealed that inhibition of casein kinase II could potentially shift COVID-2019's cellular environment into a more antiviral state. Casein kinase II disruption promotes the formation of stress granules, resulting in the inhibition of COVID-2019 proliferation. Silmitasertib could also potentially quell virus-provoked aberrant hyperactivation of the innate immune system by inhibition of upregulated CK2 protein kinase, preferentially restoring normal host cell cytokine regulation, and attenuating viral replication in moderate to severe COVID-19, thereby preventing disease progression and improving clinical outcomes.

In December 2013, Senhwa Biosciences acquired silmitasertib from Cylene Pharmaceuticals. The latter ceased operations in 2013 [1] .

In December 2020, Horizon Discovery was acquired by PerkinElmer [2] .

As at October 2021, no recent reports of development had been identified for phase-I development in Giant-lymph-node-hyperplasia (Late-stage disease) in USA (PO, Capsule), phase-I development in Multiple-myeloma (Late-stage disease) in USA (PO, Capsule), phase-I development in Solid-tumours (Late-stage disease) in USA (PO, Capsule).

Company Agreements

In June 2018, Senhwa Biosciences entered into a clinical trial agreement with the Paediatric Brain Tumor Consortium (PBTC), for the treatment of recurrent medulloblastoma. As per the agreement terms, PBTC will conduct a phase I/II and surgical study in children and adults with recurrent medulloblastoma. The trial will be sponsored by the PBTC and funded through the Consortium grant awarded by the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI). The trial will also be funded externally. [3]

Cylene Pharmaceuticals Inc. and Horizon Discovery Ltd. entered into a collaboration to maximise potential patient benefit from silmitasertib, in October 2010. The collaboration will use Horizon's X-MAN™ proprietary human isogenic cancer cell-lines to detect patients who will best respond to silmitasertib. This approach may decrease development times and provide increased success in clinical trials of the drug [4] . However it is unclear if Horizon are collaborating with Senhwa Biosciences.

Key Development Milestones

Community-acquired pneumonia

In March 2024, Senhwa Biosciences initiated a phase II trial to evaluate the safety and efficacy of silmitasertib in combination with standard of care (SOC) for treating patients with community-acquired pneumonia (CAP) associated with SARS-CoV-2 and influenza viral infections (NCT06202521; CX-4945-011). The multi-center, double-blind, randomised, interventional trial intends to enroll approximately 136 participants in Taiwan [5] . In the same month, first patient was dosed in the trial [6] . Earlier, in December 2023, Senhwa Biosciences announced that the Taiwan Food and Drug Administration had approved its phase II IND application of silmitasertib to treat patients with community-acquired pneumonia (CAP) caused by viral infection [7] .

In November 2023, US FDA approved an IND application for phase II trial of silmitasertib for treating patients with community-acquired pneumonia (CAP) caused by viral infection. Senhwa Biosciences plans a phase II trial in community-acquired pneumonia to investigate whether early intervention of Silmitasertib restrains the progression of CAP by inhibiting the elevated cytokine release associated with SARS-CoV-2 and Influenza viruses [8] . Earlier in October 2023, Senhwa Biosciences submitted the IND [9] .

COVID-2019 infections

In September 2021, Senhwa Biosciences completed a phase II investigator-initiated trial (IIT) that assessed the safety and tolerability, possible clinical benefits of silmitasertib and recovery time of the patients with COVID-2019 infections (CX4945 AV01-IIT; NCT04663737). The single-center, open-label, randomised-controlled interventional prospective trial was initiated in December 2020 and enrolled 20 patients in the US [10] . In August 2021, Senhwa Biosciences completed patient enrolment in phase II investigator-initiation trial (IIT) [11] . In September 2021, Senhwa Biosciences announced that no serious adverse events (SAEs) were reported in the trial [12] .

In November 2023, Senhwa Biosciences initiated a phase II trial to evaluate the safety and human efficacy of Silmitasertib in treating COVID-19. The prospective, proof of concept study trial intends to enroll patients in Taiwan. In the same month, the company announced that the first patient was dosed in the trial [13] . In April 2023, Taiwan FDA approved IND application for its phase II trial of silmitasertib(CX 4945) for the treatment of hospitalised patients with moderate to severe COVID-2019 infections [14] [15] .

In October 2022, University of Arizona and enhwa Biosciences terminated a phase II trial due to lack of qualifying hospitalized COVID-19 patients. The trial was designed to evaluate safety and efficacy and to explore the benefits of silmitasertib in patients with severe COVID-2019 infections (NCT04668209; CX4945-AV02-IIT). The randomised, open-label trial initiated in January 2021 enrolled 31 patients in the US [16] . In August 2021, Senhwa Biosciences announced that it had received a positive feedback from an Independent Data Monitoring Committee (DMC) for their interim review of phase II Investigator Initiated Trial in patients with severe COVID-2019 infections. The committee's initial evaluation occurred on March 2021 when they reviewed data from the first batch of randomised patients and stated that there was no need for trial modifications. An additional interim data evaluation on August 2021 of 20 patients, continues to bolster the decision to proceed with the recruitment of patients with severe COVID-19, as per the overall study design, again without any protocol modifications needed [17] . In October 2021, efficacy and safety data from phase II trial was released by the company [18] .

In June 2021, Senhwa Biosciences submitted an Investigational New Drug (IND) application to Central Drugs Standard Control Organization (CDSCO) for a planned phase II, randomized-controlled study to assess the safety, clinical benefit, and anti-viral activity of silmitasertib in up to 50 patients hospitalized with COVID-2019 infections in India [19] .

As of June 2023, Senhwa Biosciences initiated a phase II trial to evaluate safety and efficacy of silmitasertib in hospitalized adult patients. The randomised, double blinded, placebo controlled trial intends to enrol 40 patients in Taiwan (Senhwa Biosciences pipeline, June 2023).

In August 2021, Senhwa and Taiwan's CDE entered an agreement to facilitate the development of silmitasertib for treating COVID-19 in Taiwan. Under the guidance of Taiwan's CDE, Senhwa plans to launch a COVID-19 clinical trial in Taiwan to further examine the safety and human efficacy of silmitasertib in treating COVID-19. Earlier, in June 2021, Senhwa Biosciences initiated providing silmitasertib under compassionate use for patients with severe COVID-2019 infections in Taiwan [20] [19] .

In November 2020, the US FDA granted study may proceed letter to Banner – University Medical Center Phoenix. The Banner phase II investigator-initiated trial (IIT) intends to enrol 40 hospitalized patients with severe COVID-2019 infections [10] .

In November 2020, Senhwa Biosciences and its partner, Center for Advanced Research and Education (CARE), received a Study May Proceed letter from the US FDA to begin a planned phase II investigator-initiated trial evaluating silmitasertib in patients with moderate COVID-2019 infections. The open-label, randomised-controlled, investigator-initiated, phase II trial will enroll 20 patients with moderate COVID-2019 infections [21] .

In November 2020, Senhwa Biosciences submitted an investigational new drug (IND) application with the US FDA to evaluate silmitasertib in the treatment of patients with severe COVID-19 infection. The phase II multi-center, randomised, two-armed controlled interventional prospective trial will assess the safety, clinical benefit, and anti-viral activity of silmitasertib in approximately 40 patients with severe COVID-19 infection [22] . As at September 2020, Senhwa Biosciences is conducting a clinical trial of silmitasertib in patient with COVID-2019 infection. In August 2020, the US FDA approved the first emergency IND and authorised use of silmitasertib in a patient with severe COVID-19 pneumonia, not responsive to remdesivir, dexamethasone and antibiotics and requiring supplemental oxygen. Following treatment with silmitasertib, significant clinical improvement was observed and the oxygen requirement was weaned to room air the patient was discharged from the hospital within five days of treatment. The eIND application was filed by Senhwa Biosciences before August 2020 [23] [24] .

In November 2020, Senhwa Biosciences announced intention to initiate a investigator-initiated separate phase II trial to be conducted at the Center for Advanced Research and Education (CARE) in Georgia. The CARE trial will enroll approximately 20 patients once authorized by the US FDA [22] .

In June 2023, Senhwa Biosciences completed the phase I trial that evaluated the safety and tolerability of silmitasertib in healthy adult volunteers (NCT05817708; CX4945-AV04-phase I). The open-label, parallel trial was initiated in November 2022 and enrolled 30 participants in Taiwan [25] .

As of March 2020, Senhwa Biosciences is evaluating the potential Silmitasertib for the treatment COVID-2019 infections. The company also announced that upon meeting specific criteria, it intends to provide the drug free of charge to any hospitals, physicians or research units that elect to treat COVID-19 patients [26] . In June 2020, data from in-vitro analysis demonstrated anti viral activity of silmitasertib against COVID-19 infections [27]

Cancer indications

In January 2022, the US FDA granted Orphan Drug Designation (ODD) for silmitasertib for the treatment of patients with biliary tract cancer [28] .

In August 2021, the US FDA granted fast track designation to Senhwa Bioscience's silmitasertib for the treatment of patients with recurrent sonic hedgehog (SHH) driven medulloblastoma [29] .

In December 2021, the US FDA granted orphan drug designation to Senhwa Bioscience's silmitasertib for the treatment of medulloblastoma [30] .

In July 2020, the US FDA granted Rare Pediatric Disease (RPD) designation to silmitasertib for treatment for recurrent sonic hedgehog (SHH) medulloblastoma. With the RPD designation, Senhwa Biosciences is eligible for a Priority Review Voucher (PRV) which can be used for a subsequent marketing application, and may be sold or transferred [31] .

In April 2019, Senhwa Biosciences initiated and enrolled first patient in a phase I trial to determine the recommended phase II dose (RP2D) and schedule of silmitasertib when administered orally twice daily for 28 consecutive days, in a 4 week (28 days) cycle, in patients with locally advanced or metastatic basal cell carcinoma (BCC) (NCT03897036; CX-4945-07). The trial will also evaluate the preliminary efficacy, safety and tolerability of silmitasertib. The non-randomised, open-label trial will enrol approximately 26 patients in the US. In March 2022, efficacy data obtained from a phase I trial was released by Senhwa Biosciences [32] [33] [34] .

In March 2024, Pediatric Brain Tumor Consortium suspended the phase I/II trial due to drug supply issues. Earlier, in March 2019, Pediatric Brain Tumor Consortium (PBTC), in collaboration with St. Jude Children's Research Hospital and National Cancer Institute (NCI), had initiated the trial to assess the safety, efficacy, pharmacokinetics and maximum tolerated dosage of silmitasertib in patients with recurrent sonic hedgehog (SHH) medulloblastoma (PBTC-053; NCT03904862). The non-randomised trial had intended to enrol approximately 60 participants in the US [35] . The trial is sponsored by PBTC and is funded through the Consortium grant awarded by the NIH Cancer Therapy Evaluation Program (CTEP) [30] .

In June 2018, Senhwa Biosciences reported that subject to positive results from a planned phase I/II trial, the company may apply for fast track designation for silmitasertib, for the treatment of recurrent medulloblastoma [3] .

In December 2016, the US FDA granted orphan drug designation to silmitasertib (CX 4945) for the treatment of cholangiocarcinoma [3] [36] .

In June 2014, Senhwa Biosciences initiated a phase Ib/II trial to evaluate the safety and tolerability of silmitasertib, in combination with gemcitabine and cisplatin, compared to gemcitabine and cisplatin alone, in the front-line treatment of patients with cholangiocarcinoma (S4-13-001; NCT02128282). The randomised, open-label trial will enrol approximately 216 patients in the US, South Korea, and Taiwan. The study met its primary endpoint during an interim analysis by demonstrating a statistically significant difference in the silmitasertib plus gemcitabine and cisplatin arm. Earlier, Senhwa obtained authorisation from the South Korean Ministry of Food and Drug Safety to conduct the trial in South Korea, in January 2015. Approval to start the trial in Taiwan was granted by the Taiwan Food and Drug Administration, in October 2015. The combination regimen was safe, well tolerated and acted synergistically to display a favourable clinical activity, according to the phase I data released in December 2016. In January 2021, interim efficacy and adverse events data from the phase Ib/II trial were released by the Company [37] [38] [39] [40] [41] [42] .

In November 2018, the US FDA approved IND application for silmitasertib, for the treatment of basal cell carcinoma [43] .

Following positive data from preclinical and phase I trials, Cylene planned to advance silmitasertib into randomised phase II combination therapy trials. One of these will be with gemcitabine/carboplatin in ovarian cancer, and another will be with erlotinib in non-small cell lung cancer (NSCLC) [44] [45] [46] .

As of July 2020, a third phase I trial for cancer has been completed in the US [31] .

In September 2011, Cylene Pharmaceuticals completed a dose-escalating, phase I trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral silmitasertib in patients with relapsed or refractory multiple myeloma(C4-09-001; NCT01199718). The open-label trial, initiated in September 2010, enrolled 22 patients in the US [31] [47] [48] .

In December 2011, Cylene Pharmaceuticals completed a phase I trial designed to determine the safety, tolerability, and pharmacokinetics of silmitasertib in patients with advanced solid tumours, Castleman's disease, or multiple myeloma was initiated in the US (C4-08-001; NCT00891280). The open-label trial, initiated in January 2009, enrolled 55 patients in the US [49] [50] . Interim results for 17 patients have been reported [31] [51] [52] .

In April 2021, Ohio State University College of Medicine and Penn State University College of Medicine presented data at the 112th Annual Meeting of the American Association for Cancer Research (AACR-2021) demonstrating treatment with silmitasertib, enhanced ikaros activity as a repressor of MTOR, resulting in reduced expression of MTOR in high-risk B-cell acute lymphoblastic leukemia (HR B-ALL). Combination treatment with rapamycin and silmitasertib showed synergistic therapeutic effects in vitro and in patient-derived xenografts from HR B-ALL [53] .

In December 2023, pharmacodynamic data from preclinical study in precursor T-cell acute lymphoblastic lymphoma were presented at the 65th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2023) [54] .

In June 2020, the company presented pharmacodynamics data from a preclinical study in precursor B-cell lymphoblastic leukaemia lymphoma at the 111th Annual Meeting of the American Association for Cancer Research - II (AACR-2020) [55] .

As of April 2023, preclinical development for the treatment of acute myeloid leukemia is underway in the US. In April 2023, Penn State College of Medicine presented data from the in vivo study at the 114th Annual Meeting of the American Association for Cancer Research (AACR-2023) [56] .
In April 2023, Penn State College of Medicine presented data from preclinical studies in precursor cell lymphoblastic leukaemia lymphoma at the 114th Annual Meeting of the American Association for Cancer Research (AACR-2023) [57]

As at June 2018, Stanford University School of Medicine was conducting preclinical development in the treatment of recurrent medulloblastoma [3] .

Cylene Pharmaceuticals presented data on silmitasertib, at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Berlin, Germany in November 2010. The company presented clinical data as well as investigations into the role that silmitasertib plays in the DNA damage response and epidermal growth factor receptor (EGFR) pathways [58] [59] [60] [61] .

Results from preclinical studies have been reported [62] [63] [64] [65] .

Financing information

In December 2013, Senhwa Biosciences completed a $US17 million Series B round of financing. Part of the proceeds will be used to advance silmitasertib through clinical proof-of-concept studies [66] .

Cylene closed $US12 million in financing from existing investors in September 2010. These funds will be used to finance existing phase I trials and to conduct a series of randomised phase II trials [48] .

Drug Properties & Chemical Synopsis

  • Route of administration PO
  • Formulation Capsule, unspecified
  • Class 3-ring heterocyclic compounds, Antineoplastics, Antivirals, Carboxylic acids, Naphthyridines, Small molecules
  • Target Casein kinase II
  • Mechanism of Action Casein kinase II inhibitors
  • WHO ATC code

    L01X-E (Protein kinase inhibitors)

  • EPhMRA code

    L1H (Protein Kinase Inhibitor Antineoplastics)

  • Chemical name 5-(3-Chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid
  • Molecular formula C19 H12 Cl N3 O2
  • SMILES C1=NC=CC2=C1C1=C(N=C2NC2=CC(=CC=C2)Cl)C=C(C=C1)C(O)=O
  • Chemical Structure
  • CAS Registry Number 1009820-21-6

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

basal cell cancer

Outcome Measure

GLI1

1

carcinoma

Outcome Measure

GLI1

1

COVID 2019 infections

Outcome Measure

phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha

Interleukin-6 (IL-6)

Ferritin

D-dimer

Creatine

C-reactive protein (CRP)

2

2

2

2

1

2

medulloblastoma

Arm Group Description

sonic hedgehog

1

medulloblastoma

Detailed Description

sonic hedgehog

1

medulloblastoma

Eligibility Criteria

sonic hedgehog

1

medulloblastoma

Official Title

sonic hedgehog

1

medulloblastoma

Brief Summary

sonic hedgehog

1

Biomarker

Drug Name Biomarker Name Biomarker Function
Silmitasertib - Senhwa Biosciences C-reactive protein (CRP) Outcome Measure
Creatine Outcome Measure
D-dimer Outcome Measure
Ferritin Outcome Measure
GLI1 Outcome Measure
Interleukin-6 (IL-6) Outcome Measure
L-Serine Arm Group Description
L-Threonine Arm Group Description
phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha Outcome Measure
sonic hedgehog Arm Group Description, Brief Summary, Detailed Description, Eligibility Criteria, Official Title
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Acute myeloid leukaemia - - Preclinical USA PO / unspecified Penn State College of Medicine 14 Apr 2023
Basal cell cancer - Metastatic disease, Second-line therapy or greater Phase I USA PO / Capsule Senhwa Biosciences 01 Apr 2019
COVID 2019 infections - - Phase II Taiwan, USA PO / Capsule Senhwa Biosciences 15 Jun 2023
COVID 2019 infections - In volunteers Phase I Taiwan PO / unspecified Senhwa Biosciences 07 Nov 2022
Cholangiocarcinoma - Combination therapy, First-line therapy Phase I/II South Korea, Taiwan, USA PO / Capsule Senhwa Biosciences 28 Jan 2015
Community-acquired pneumonia Associated With SARS-CoV-2 and Influenza Viral Infections Combination therapy Phase II Taiwan PO / unspecified Senhwa Biosciences 20 Mar 2024
Giant lymph node hyperplasia Castleman's disease Late-stage disease No development reported (I) USA PO / Capsule Senhwa Biosciences 28 Oct 2021
Medulloblastoma 3 years and older; recurrent SHH (Sonic Hedgehog) medulloblastoma In adolescents, In adults, In children, In the elderly, Recurrent, Second-line therapy or greater Phase I/II USA (fast track) PO / Capsule Stanford University School of Medicine 18 Mar 2019
Multiple myeloma - Late-stage disease No development reported (I) USA PO / Capsule Cylene Pharmaceuticals 28 Oct 2021
Precursor B-cell lymphoblastic leukaemia-lymphoma - - Preclinical Taiwan unspecified / unspecified Senhwa Biosciences 01 Jun 2020
Precursor T-cell lymphoblastic leukaemia-lymphoma - - Preclinical China unspecified / unspecified Cylene Pharmaceuticals 09 Dec 2023
Solid tumours - Late-stage disease No development reported (I) USA PO / Capsule Senhwa Biosciences 28 Oct 2021

Priority Development Status

Type Region Indication
Fast Track USA Medulloblastoma

Orphan Status

Indication Patient Segment Country Organisation Event Date
Biliary cancer - USA Senhwa Biosciences 20 Jan 2022
Cholangiocarcinoma - USA Senhwa Biosciences 31 Dec 2016
Medulloblastoma - USA Senhwa Biosciences 17 Dec 2021

Commercial Information

Involved Organisations

Organisation Involvement Countries
Cylene Pharmaceuticals Originator USA
Senhwa Biosciences Owner Taiwan
National Cancer Institute (USA) Funder USA
Ohio State University Medical Center Collaborator USA
Horizon Discovery Collaborator England
University of Arizona Collaborator USA
Center for Advanced Research and Education Collaborator USA
Pediatric Brain Tumor Consortium Collaborator USA
Stanford University School of Medicine Collaborator USA
Penn State College of Medicine Collaborator USA

Scientific Summary

Pharmacokinetic Measures

Characterstic Measure
Linear Kinetics yes
T½beta (h) 25 (Adult)

Pharmacokinetics

Clinical

Interim results of a phase I trial showed linear pharmacokinetics of silmitasertib in patients with advanced solid tumours. Thirteen such patients (3-4 patients per cohort, from four separate dose cohorts) received oral, twice-daily or four-times daily doses of silmitasertib for 21 consecutive days of a 4-week cycle. Further interim results demonstrate that plasma exposure at steady state of silmitasertib is significantly increased in patients dosed four-times daily compared with those dosed twice-daily. The trial design provided for administration of silmitasertib in successive dose cohorts at 90mg, 160mg, 300mg, 460mg, 700mg and 1000mg per dose. General linearity in pharmacokinetic parameters was observed between the dose cohorts. At steady state, the terminal half-life was approximately 25 hours [59] [51] [52] .

Preclinical

In preclinical studies, silmitasertib showed favourable pharmacokinetics and oral bioavailability in multiple species [65] .

Adverse Events

In a phase Ib/II trial, the combination of silmitasertib plus gemcitabine and cisplatin compared to gemcitabine and cisplatin alone in the frontline treatment of patients (n = 88) with cholangiocarcinoma (CCA) was found to be safe. Almost all patients receiving silmitasertib (99%) experienced at least 1 TEAE (Treatment-Emergent Adverse Events), although most were mild or moderate in severity. The most common silmitasertib treatment-related TEAEs were diarrhea (66%), nausea (51%), vomiting (33%), and fatigue (31%). The TEAE profile of silmitasertib compares favorably with that of gemcitabine and cisplatin in the BT22 study (which included 6-weekly tumor scans; the BT22 study looked at gemcitabine alone verses gemcitabine and cisplatin in combination), with a lower incidence of hematological AEs (Adverse Events) of 21–39% versus 58.5–87.8%. 66% of patients had a reduction in their CA 19-9 levels [37] [42] .

Interim results of a phase I trial showed that silmitasertib was well-tolerated in patients with solid tumours. Thirteen such patients (3-4 patients per cohort, from four separate dose cohorts) received oral, twice-daily doses of silmitasertib for 21 consecutive days of a 4-week cycle. The trial design provided for administration of silmitasertib in successive dose cohorts at 90mg, 160mg, 300mg, 460mg, 700mg and 1000mg per dose. No adverse events of grade ≥3 were reported. No dose-limiting toxicities had been observed and the maximum tolerated dose was yet to be defined. Further enrolment to planned dose escalation cohorts was continuing at the time of reporting the interim results [52] . In further results for 17 patients in 5 dose cohorts (90, 160, 300, 460 and 700mg), no dose-limiting toxicities had been observed [51] . After expansion of this study, which included a patient cohort dosed four-times daily, no dose-limiting toxicities were reported at either the twice-daily or four-times daily dosing schedules. Silmitasertib is well tolerated at both dosing schedules and the maximum tolerated dose (MTD) is yet to be reached [59] .

COVID-2019 infections

Results from a phase II trial in 20 patients with moderate COVID-19 symptoms showed that silmitasertib was well tolerated with a good safety profile. No severe adverse events related to silmitasertib treatment group were observed [18] [69] .

Pharmacodynamics

Summary

Clinical studies

Interim results from a phase I trial demonstrated that silmitasertib inhibited the CK2 and Akt pathways (downstream pathway biomarker) in an exposure-related manner in patients with advanced solid tumours. Inhibition associated with silmitasertib treatment was shown to be mediated via reduced phosphorylation of Akt and p21 proteins in peripheral blood mononuclear cells (PBMCs). This effect on the Akt and p21 biomarkers was shown in previously reported interim results. Patients were randomised into cohorts, and received successive silmitasertib doses of 90, 160, 300, 460 and 700mg twice- or four-times daily over 21 consecutive days in a four-week cycle [59] [51] [44] .

Preclinical studies

Silmitasertib in combination with erlotinib, an EGFR-targeted drug, inhibited phosphorylation of AKT and ribosomal protein S6 greater than either agent given alone in a breast cancer cell model. The combined treatment resulted in the synergistic killing of cancer cells and tumour growth inhibition in xenograft breast cancer models [60] .

Silmitasertib was shown to enhance the anti-tumour activity of EGFR-targeted agents in vitro and in vivo, by attenuating signaling in the PI3K/AKT/mTOR pathway. Silmitasertib plus erlotinib resulted in enhanced reduction in phosphorylation of AKT (T308 and S473), PRAS40 (S246), mTOR (S2481 and S2448), p70S6K1 (T389), S6 (S235/6 and 240/4) and 4E-BP1 (T37/46), and decreased Mcl-1 levels. These effects were accompanied by decreased cell proliferation and synergistic induction of apoptosis. Silmitasertib plus erlotinib showed enhanced anti-tumour activity in A431 squamous cell carcinoma and NCI-H2170 non-small cell lung carcinoma (NSCLC) xenograft models. In the erlotinib-resistant NCI-H1975 NSCLC xenograft model, silmitasertib plus cetuximab resulted in enhanced efficacy [68] .

The addition of silmitasertib to gemcitabine treatment resulted in enhanced antitumour activity of the latter in A2780 cells (an ovarian cancer cell line). Silmitasertib enhanced activity via the disruption of the DNA damage repair pathway and down-regulation of anti-apoptotic mediators [61] .

In vitro,

in breast cancer cell lines, cells carrying mutations that caused Akt activation were significantly more sensitive on exposure to silmitasertib than cells that lacked such mutations. Reduced phosphorylation of Akt at Ser129 and reduced phosphorylation of p21 (a downstream target of Akt) were noted in the presence of silmitasertib. Synergistic antiproliferative activity was noted in breast cancer cells on exposure to a combination of silmitasertib and inhibitors targeting the phosphatidylinositol-3-kinase/Akt pathway [62] .

Silmitasertib showed anti-proliferative activity against various tumour cell lines including inflammatory breast cancer cells, and was selective for CK2 when compared with over 100 protein kinases. Silmitasertib inhibited CK2 activity in Jurkat cells with an IC50 of 100 nmol/L, and induced cell line-dependent G1 or G2 cell cycle arrest. Silmitasertib showed dose- and time-dependent dephosphorylation of p21 in multiple cell lines and induced apoptosis by activation of caspase 3/7. In BxPC3 xenografts, 70% tumour-free survival was observed after treatment with silmitasertib [65] .

Silmitasertib has shown broad anti-proliferative activity against multiple cancer cell-lines and has demonstrated anti-tumour activity in xenograft models. Suppression of PI3K/AKT signalling was observed in BxPC3 pancreatic cells and cultured HUVEC cells. Silmitasertib also demonstrated consistent concentration dependent inhibition of phosphorylation of p21 at the T145 site in multiple cancer cell-lines and in PBMCs isolated from nu/nu mice receiving oral silmitasertib [64] .

Silmitasertib inhibited pro-angiogenic CK2 signalling in vitro which indicated its antitumour activity in vivo. In BxPC-3 cells, treatment with silmitasertib under hypoxic conditions prevented downregulation of p53 and pVHL and blocked Hif-1α transcription activation. The compound inhibited human umbilical vein endothelial cell (HUVEC) proliferation at IC50 of 5.5µmol/L, migration at IC50 of 4.0µmol/L and tube formation at IC50 of 2.0µmol/L. Moreover, silmitasertib inhibited AKT signalling in HUVECs and had a marked effect on cellular morphology [63] .

Silmitasertib demonstrated a synergistic effect with venetoclax (p < 0.05) in 8 of 9 cell lines tested, across a dose range of (0.01 - 10 µM venetoclax) and independently of the timepoints (6-48 hour) analysed. Drug sensitivity profiling of vanateoclax and silmitasertib single and combined treatments in BCP- and T-ALL cell lines indicated an up to 80% increased anti-proliferative and pro-apoptotic efficacy after combination treatment. Synergism was more pronounced in cells with the lowest basal sensitivity to venetoclax. Primary patient material using ex vivo treated BCP-ALL patient derived xenograft cells (n=17) and stroma co-cultures of patient samples (n = 14) confirmed the findings. The combination significantly decreased viability in all patient samples, compared to the single agent, irrespective of the heterogeneity of sensitivity towards single treatments [67] .

Results from an AML xenograft mice treated with a combination of silmitasertib and cytarabine have decreased leukemia burden and prolonged survival compared to either drug alone. Silmitasertib showed in vivo therapeutic efficacy in AML patient-derived xenografts.Cytarabine-resistant cells have high expression of CK2. Gene expression analysis showed that the cytarabine metabolism gene is significantly altered in cytarabine-resistant cells and silmitasertib -treated AML cells. In cytarabine resistant cells, NT5C2 has been found to be high while hENT1 is low, preventing ideal cytarabine metabolism. Silmitasertib treatment decreased the expression of NT5C2 and increases expression of hENT1. Cytarabine sensitivity is restored following genetic inhibition (shRNA) or treatment with a CK2 inhibitor [56] .

In preclinical studies, CX 4945 induced apoptotic cell death in B and T acute lymphoblastic leukemia (ALL) cell lines with IC50 concentrations ranging between 4-10 µM. CX 4945 treatment significantly affected the glucose consumption in NALM6 cells. Similarly, substantial decrease in intracellular ATP and lactate levels compared to vehicle was recorded. CK2α inhibition significantly decreased the glycolytic activity in B- and T-ALL cell lines. It was observed that glycolytic reserves were significantly decreased in 697 (3-fold), MOLT4 (4-fold), CEM (3-fold) cells incubated with CX 4945 in comparison to vehicle. The principal component analysis from metabolomics study showed a clear separation between CX 4945 and vehicle-treated NAML6 cells. Sixty-four statistically significant, differentially expressed metabolites were recorded in the study. Analyte classes included TCA cycle intermediates, nucleic acids and their precursors as well as glycolysis intermediates that were significantly affected by CK2α inhibition [57] .

Pharmacodynamic data from preclinical studies in precursor T-cell acute lymphoblastic leukemia (T-ALL) showed that the combination of CX-4945 with WDR5 inhibition as a potential option for the therapy of T-ALL patients. WDR5 knockdown in T-ALL cells significantly suppressed cell proliferation and induced cell cycle arrest in vitro (P<0.01) and in vivo leukemia development. Also, WDR5 inhibitor OICR-9429 induced cell proliferation and cell cycle arrest in the cells. ATAD2 was downregulated upon OICR-9429 treatment and indicated that ATAD2 is the downstream target of WDR5. WDR5 knockdown suppressed ATAD2 expression (P<0.01). In addition, ATAD2 was highly expressed in T-ALL patients versus normal controls (P<0.05), and ATAD2 silencing significantly suppressed cell proliferation and induced cell cycle arrest of T-ALL cells (P<0.01). CX-4945 strongly suppressed WDR5 expression in an IKAROS-dependent manner. The synergistic effect of CX-4945 with WDR5 disruption on cell proliferation suppression and cell cycle arrest was observed in T-ALL both in in vitro and in vivo xenograft mouse model. The combination of CX-4945 with WDR5 disruption significantly prolonged the survival of mice compared with single CX-4945 [55(52-58) days vs. 38.5(36-41) daysP<0.001] and single WDR5 disruption control [55(52-58) days vs. 41.5(39-44) days, P<0.001]. Consistently, the combination significantly reduced the size and weight of the spleen, % human CD45+ T-ALL cells in the spleen and bone marrow, and the expression of WDR5 and ATAD2 in the spleen versus single treatment controls (P<0.01). A synergistic effect of CX-4945 with OICR-9429 on cell proliferation suppression and down-regulation of WDR5 and ATAD2 was observed in the primary leukemic cells from T-ALL patients [54] .

In preclinical studies silmitasertib was shown to inhibit viral replication in infected cells and also reduced the body's over active inflammatory response to the SARS-CoV-2 infection [11] .

Therapeutic Trials

In a phase Ib/II trial, the combination of silmitasertib plus gemcitabine and cisplatin compared to gemcitabine and cisplatin alone in the frontline treatment of patients (n = 88) with cholangiocarcinoma (CCA), met its primary endpoint during an interim analysis by demonstrating a statistically significant difference in the silmitasertib plus gemcitabine and cisplatin arm. The efficacy findings for silmitasertib compare favorably with those reported in the literature for gemcitabine and cisplatin in the BT22 study (which included 6-weekly tumor scans; the BT22 study looked at gemcitabine alone verses gemcitabine and cisplatin in combination). Median PFS in the modified intent-to-treat (mITT) population (11.2 months) is a clinically meaningful improvement when compared to the study's phase II control group (5.8 months). PFS was approximately 5 months longer than in the BT22 study (5.8 months). Median OS (Overall Survival) in the mITT population (17.4 months) was approximately 6 months longer than in the BT22 study (11.2 months). The ORR (Overall Response Rate) in the mITT population (32.1%) was higher than in the BT22 study (19.5%). The DCR (Disease Control Rate in the mITT population (79.3%) was also higher than that in the BT22 study (68.3%). These findings indicate a clinically meaningful improvement in progression-free survival (PFS) (P<0.05) [37] [42] .

Interim data from a phase I trial of silmitasertib in patients with solid tumours have shown that 20% of evaluable patients had disease stabilisation for ≥16 weeks (4 months), with 67% of these patients remaining on study for ≥6 months [44] . These results were similar to earlier reported results from 23 evaluable patients with advanced solid tumours with progressive disease (or having no available approved therapies) enrolled so far in a phase I trial. Six of 23 patients showed stable disease at first evaluation and 4/23 patients maintained stable disease at ≥6 months, including 2 patients on treatment for >9 months. Patients were randomised into cohorts and received successive silmitasertib doses of 90, 160, 300, 460 and 700mg twice- or four-times daily over 21 consecutive days in a 4-week cycle [59] .

Efficacy data obtained from a phase I trial indicated that at week 24, two patients out of ten, experienced a partial response (30% decrease in tumour size). At week eight, more than 90% decrease of GLI-1 expression was reported after the first biopsy analysis [32] [34] .

COVID-2019 infections

Results from phase II trial of silmitasertib in USA in intent to treat population demonstrated statistically significant and clinically meaningful 133% faster time in recovery of COVID-19-related clinical symptoms (Median: 6 days vs 14 days, p=0.0167, one-sided Type-1 error 0.20), 114% faster in time to reach EQ-5D-5L Q6 = 90% versus SOC/best supportive care (Median: 14 days vs 30 days, p=0.1835, one-sided Type-1 error 0.20) and 57% faster in time to normalization of COVID-19-related clinical signs versus SOC/best supportive care (Median: 7 days vs 11 days, p=0.0557, one-sided Type-1 error 0.20) [18] . Earlier in a clinical trial, treatment with silmitasertib in first patient with COVID-2019 demonstrated significant clinical improvement and the oxygen requirement was weaned to room air. The patient was discharged from the hospital following five days of treatment [23] [24] [69]

Future Events

Expected Date Event Type Description Updated
30 Apr 2019 Trial Update Senhwa Biosciences and Pediatric Brain Tumor Consortium plans a phase I/II trial for Medulloblastoma in April 2019 in USA (PO, Capsule) (NCT03904862) (700296664) 08 May 2023

Development History

Event Date Update Type Comment
20 Mar 2024 Phase Change - II Phase-II clinical trials in Community-acquired pneumonia (Combination therapy) in Taiwan (PO) [6] (NCT06202521) Updated 25 Mar 2024
08 Mar 2024 Trial Update Pediatric Brain Tumor Consortium suspends phase I/II clinical trial in Medulloblastoma (Second-line therapy or greater, Recurrent, In adolescents, In adults, In children, In the elderly) in USA (PO) due to drug supply issues(NCT03904862) Updated 18 Mar 2024
26 Dec 2023 Regulatory Status Taiwan FDA approves IND application for Silmitasertib in Community-acquired pneumonia [7] Updated 28 Dec 2023
26 Dec 2023 Trial Update Senhwa Biosciences plans a phase-II trial for Community-acquired pneumonia in Taiwan [7] Updated 28 Dec 2023
09 Dec 2023 Phase Change - Preclinical Preclinical trials in Precursor T-cell lymphoblastic leukaemia-lymphoma in China (unspecified route) [54] (Prior to December 2023) Updated 30 Jan 2024
09 Dec 2023 Scientific Update Pharmacodynamic data from preclinical studies in Precursor T-cell acute lymphoblastic leukemia presented at the 65th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2023) [54] Updated 30 Jan 2024
21 Nov 2023 Regulatory Status US FDA approves IND application for Silmitasertib in Community-acquired pneumonia [8] Updated 24 Nov 2023
09 Nov 2023 Trial Update Senhwa Biosciences initiates enrolment in a phase II trial for COVID-2019 infections in Taiwan (PO) Updated 20 Nov 2023
19 Oct 2023 Trial Update Senhwa Biosciences plans a phase II trial for Community-acquired pneumonia (PO) in USA [9] Updated 31 Oct 2023
19 Oct 2023 Regulatory Status Senhwa Biosciences files an Investigational New Drug (IND) application for phase II trial in Community-acquired pneumonia in USA [9] Updated 23 Oct 2023
25 Aug 2023 Active Status Review 700327753- Trial termination info added in KDM and HE; Trial completion date has been considered as trial termination date; Trial completion HE has kept unpublished Updated 25 Aug 2023
20 Jun 2023 Trial Update Senhwa Biosciences completes the phase trial in COVID-2019 infections (In volunteers) in Taiwan (PO) (NCT05817708) Updated 08 Jan 2024
15 Jun 2023 Active Status Review Silmitasertib is still in phase-I development in Basal-cell-cancer in USA (Senhwa Biosciences pipeline, June 2023) Updated 15 Jun 2023
15 Jun 2023 Phase Change - II Phase-II clinical trials in COVID-2019 infections in Taiwan, prior to June 2023 (PO) (Senhwa Biosciences pipeline, June 2023) Updated 15 Jun 2023
28 Apr 2023 Regulatory Status Taiwan FDA approves IND application for silmitasertib in COVID-2019 infections [15] Updated 03 May 2023
14 Apr 2023 Scientific Update Pharmacodynamics data from a preclinical study in Precursor cell lymphoblastic leukaemia lymphoma presented at the 114th Annual Meeting of the American Association for Cancer Research (AACR-2023) [57] Updated 02 Jun 2023
14 Apr 2023 Phase Change - Preclinical Preclinical trials in Acute myeloid leukaemia in USA (PO), prior to April 2023 [56] Updated 29 May 2023
14 Apr 2023 Scientific Update Pharmacodynamics data from a preclinical study in acute myeloid leukemia presented at the 114th Annual Meeting of the American Association for Cancer Research (AACR-2023) [56] Updated 29 May 2023
07 Nov 2022 Phase Change - I Phase-I clinical trials in COVID-2019 infections (In volunteers) in Taiwan (PO) (NCT05817708) Updated 21 Apr 2023
19 Oct 2022 Trial Update University of Arizona terminates a phase II trial for COVID-2019 infections in USA due to lack of qualifying hospitalized COVID-19 patients (NCT04668209) Updated 25 Aug 2023
19 Oct 2022 Trial Update University of Arizona completes a phase II trial for COVID-2019 infections in USA (NCT04668209) Updated 18 Nov 2022
28 May 2022 Phase Change - No development reported No recent reports of development identified for phase-I development in Basal-cell-cancer(Metastatic disease, Second-line therapy or greater) in USA (PO, Capsule) Updated 28 May 2022
28 Mar 2022 Scientific Update Efficacy data obtained from a phase I trial in Basal cell carcinoma released by Senhwa Biosciences [32] Updated 01 Apr 2022
20 Jan 2022 Regulatory Status Silmitasertib - Senhwa Biosciences receives Orphan Drug status for Biliary cancer in USA [28] Updated 07 Feb 2022
17 Dec 2021 Regulatory Status Silmitasertib - Senhwa Biosciences receives Orphan Drug status for Medulloblastoma in USA [30] Updated 21 Dec 2021
28 Oct 2021 Phase Change - No development reported No recent reports of development identified for phase-I development in Giant-lymph-node-hyperplasia(Late-stage disease) in USA (PO, Capsule) Updated 28 Oct 2021
28 Oct 2021 Phase Change - No development reported No recent reports of development identified for phase-I development in Multiple-myeloma(Late-stage disease) in USA (PO, Capsule) Updated 28 Oct 2021
28 Oct 2021 Phase Change - No development reported No recent reports of development identified for phase-I development in Solid-tumours(Late-stage disease) in USA (PO, Capsule) Updated 28 Oct 2021
22 Oct 2021 Scientific Update Efficacy and safety data from a phase II trial in COVID-2019 infections released by Senhwa Biosciences [18] Updated 22 Oct 2021
30 Sep 2021 Trial Update Senhwa Biosciences completes a phase-II CARE clinical trial in COVID-2019 infections in USA (PO) (NCT04663737) Updated 25 May 2022
22 Sep 2021 Biomarker Update Biomarkers information updated Updated 02 Oct 2021
18 Aug 2021 Regulatory Status Silmitasertib - Senhwa Biosciences receives Fast Track designation for Medulloblastoma [PO,Capsule] (In adolescents, In children, In the elderly, Recurrent, Second-line therapy or greater, In adults) in USA [29] Updated 23 Aug 2021
16 Aug 2021 Scientific Update Pharmacodynamics data from a preclinical trial in COVID-2019 infections released by Senhwa Biosciences [11] Updated 19 Aug 2021
16 Aug 2021 Trial Update Senhwa Biosciences completes enrolment in its phase II investigator initiated trial (IIT) for COVID-2019 infections in USA [11] Updated 19 Aug 2021
13 Aug 2021 Regulatory Status Senhwa Biosciences plans to obtain Emergency authorisation in COVID-2019 infections in Taiwan [20] Updated 06 Sep 2021
13 Aug 2021 Trial Update Senhwa Biosciences plans a phase II in COVID-2019 infections Taiwan [20] [15] Updated 06 Sep 2021
23 Jun 2021 Regulatory Status Senhwa Biosciences files an IND application with the Central Drugs Standard Control Organization in India for COVID-2019 infections [19] Updated 25 Jun 2021
23 Jun 2021 Trial Update Senhwa Biosciences plans a phase II for COVID-2019 infections in India [19] Updated 25 Jun 2021
01 Jun 2021 Trial Update Clinical trials (compassionate use) in COVID-2019 infections in Taiwan (PO) [19] Updated 25 Jun 2021
15 Jan 2021 Scientific Update Interim efficacy and adverse events data from a phase Ib/II trial in Cholangiocarcinoma released by Senhwa Biosciences [37] Updated 19 Jan 2021
15 Jan 2021 Trial Update Senhwa Biosciences plans a phase III trial for Cholangiocarcinoma [37] Updated 19 Jan 2021
01 Jan 2021 Trial Update University of Arizona initiates enrolment in a phase II trial for COVID-2019 infections in USA (NCT04668209) Updated 04 Feb 2021
23 Dec 2020 Company Involvement Horizon Discovery has been acquired by PerkinElmer Updated 18 Jun 2021
03 Dec 2020 Phase Change - II Phase-II clinical trials in COVID-2019 infections in USA (PO) [10] (NCT04663737) Updated 08 Dec 2020
03 Dec 2020 Trial Update Senhwa Biosciences and Banner – University Medical Center Phoenix plans an additional investigator initiated phase II trial for COVID-2019 infections in USA [10] Updated 08 Dec 2020
26 Nov 2020 Regulatory Status The Banner - University Medical Center received study may proceed letter from the US FDA for Silmitasertib for COVID-2019 infections [10] Updated 08 Dec 2020
06 Nov 2020 Regulatory Status Senhwa Biosciences received Study May Proceed letter from the US FDA for Silmitasertib in moderate COVID-2019 infections [21] Updated 10 Nov 2020
06 Nov 2020 Trial Update Senhwa Biosciences plans an investigator initiated phase II trial for moderate COVID-2019 infections in USA (PO) [21] Updated 10 Nov 2020
02 Nov 2020 Regulatory Status Senhwa Biosciences files an IND application with the US FDA for COVID-2019 infections in USA [22] Updated 04 Nov 2020
11 Sep 2020 Trial Update Senhwa Biosciences plans an investigator initiated phase II trial for severe COVID-2019 infections in USA (PO) [23] [22] Updated 23 Sep 2020
11 Sep 2020 Scientific Update Efficacy data from a clinical trial in COVID-2019 infections released by Senhwa Biosciences [23] Updated 17 Sep 2020
11 Sep 2020 Trial Update Senhwa Biosciences plans a phase II investigator initiated CARE trial in USA [23] [22] Updated 17 Sep 2020
01 Sep 2020 Phase Change - Clinical Clinical trials in COVID-2019 infections in USA (PO), before September 2020 [23] Updated 17 Sep 2020
27 Aug 2020 Regulatory Status US FDA approves the emergency IND application for COVID-2019 infections in USA [23] Updated 17 Sep 2020
04 Aug 2020 Phase Change - Preclinical Preclinical trials in COVID-2019 infections in USA (PO), prior to August 2020 (Senhwa Biosciences pipeline, August 2020) Updated 04 Aug 2020
04 Aug 2020 Regulatory Status Senhwa Biosciences intends to submit an IND application for COVID-2019 infections in USA (Senhwa Biosciences pipeline, April 2020) Updated 04 Aug 2020
01 Aug 2020 Regulatory Status Senhwa Biosciences files an emergency IND application with the US FDA in USA for COVID-2019 infections, before August 2020 [23] Updated 17 Sep 2020
07 Jul 2020 Regulatory Status Silmitasertib receives Rare Paediatric Disease Designation for Medulloblastoma in USA [31] Updated 09 Jul 2020
07 Jul 2020 Trial Update Cylene Pharmaceuticals completes a phase I trial for Cancer in USA (PO) [31] Updated 09 Jul 2020
22 Jun 2020 Scientific Update Pharmacodynamics data from a preclinical study in Precursor B-cell lymphoblastic leukaemia lymphoma presented at the 111th Annual Meeting of the American Association for Cancer Research - II (AACR-2020) [55] Updated 18 Jul 2020
11 Jun 2020 Scientific Update Pharmacodynamics data from preclinical studies in Precursor cell lymphoblastic leukaemia lymphoma presented at the 25th Congress of the European Haematology Association [67] Updated 02 Aug 2020
01 Jun 2020 Phase Change - Preclinical Preclinical trials in Precursor B-cell lymphoblastic leukaemia-lymphoma in Taiwan (unspecified route) [55] Updated 18 Jul 2020
31 Mar 2020 Phase Change Investigation in COVID-2019 infections in USA (PO) (Senhwa Biosciences pipeline, July 2020) [26] Updated 03 Apr 2020
17 Apr 2019 Trial Update Senhwa Biosciences and Pediatric Brain Tumor Consortium plans a phase I/II trial for Medulloblastoma in April 2019 in USA (PO, Capsule) (NCT03904862) Updated 08 May 2023
01 Apr 2019 Phase Change - I Phase-I clinical trials in Basal cell cancer (Metastatic disease, Second-line therapy or greater) in USA (PO) (NCT03897036) Updated 08 Apr 2019
18 Mar 2019 Phase Change - I/II Phase-I/II clinical trials in Medulloblastoma (Second-line therapy or greater, Recurrent, In adolescents, In adults, In children, In the elderly) in USA (PO) (NCT03904862) Updated 09 Aug 2019
01 Nov 2018 Regulatory Status US FDA approves IND application for silmitasertib in Basal cell carcinoma [43] Updated 09 Nov 2018
12 Sep 2018 Active Status Review Phase I development is ongoing in USA (Senhwa Biosciences pipeline, September 2018) Updated 12 Sep 2018
12 Sep 2018 Trial Update Senhwa Biosciences plans a clinical trial for Basal cell cancer (Second-line therapy or greater) (Senhwa Biosciences pipeline, September 2018) Updated 12 Sep 2018
12 Jun 2018 Licensing Status Senhwa Biosciences and Pediatric Brain Tumor Consortium enter into a clinical trial agreement for the conduction of a phase I/II trial in Medulloblastoma (Recurrent, In adults, In children, In adolescents) in USA [3] Updated 15 Jun 2018
12 Jun 2018 Phase Change - Preclinical Preclinical trials in Medulloblastoma (Recurrent) in USA (PO) [3] Updated 15 Jun 2018
12 Jun 2018 Trial Update Senhwa Biosciences and Pediatric Brain Tumor Consortium plan a phase I/II trial for Medulloblastoma (Recurrent, In adults, In children, In adolescents) in USA [3] Updated 15 Jun 2018
31 Dec 2016 Regulatory Status Silmitasertib receives Orphan Drug status for Cholangiocarcinoma in USA [3] [36] Updated 06 Jan 2017
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Giant-lymph-node-hyperplasia in USA (PO, Capsule) Updated 16 Jul 2016
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Multiple-myeloma in USA (PO, Capsule) Updated 16 Jul 2016
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Solid-tumours(Late-stage disease) in USA (PO, Capsule) Updated 16 Jul 2016
23 Oct 2015 Phase Change - I/II Phase-I/II clinical trials in Cholangiocarcinoma (Combination therapy, First-line therapy) in Taiwan (PO) after October 2015 (NCT02128282) Updated 12 Sep 2018
22 Oct 2015 Regulatory Status The Taiwan Food and Drug Administration approves clinical trial application for silmitasertib in Cholangiocarcinoma [39] Updated 13 Feb 2016
28 Jan 2015 Regulatory Status The South Korean Ministry of Food and Drugs Safety approves clinical trial application for silmitasertib in Cholangiocarcinoma [40] Updated 12 Feb 2016
17 Jun 2014 Phase Change - I/II Phase-I/II clinical trials in Cholangiocarcinoma (Combination therapy, First-line therapy) in South Korea (PO) after January 2015 Updated 11 Feb 2016
17 Jun 2014 Phase Change - I/II Phase-I/II clinical trials in Cholangiocarcinoma (first-line combination therapy) in USA (PO) Updated 19 Jun 2014
28 Apr 2014 Trial Update Senhwa Biosciences plans a phase I/II trial for Cholangiocarcinoma (first-line therapy, combination therapy) in the US (NCT02128282) Updated 12 May 2014
13 Dec 2013 Licensing Status Senhwa Biosciences acquires CX 4945 from Cylene Pharmaceuticals [1] Updated 24 Dec 2013
31 Dec 2011 Trial Update Cylene Pharmaceuticals completes a phase I trial for Solid tumours, Giant lymph node hyperplasia and Multiple Myeloma (Late-stage disease) in USA (PO) (NCT00891280) [31] Updated 09 Jul 2020
30 Sep 2011 Trial Update Cylene Pharmaceuticals completes a phase I trial for Multiple Myeloma (Late-stage disease) in USA (PO) (NCT01199718) [31] Updated 09 Jul 2020
06 Jun 2011 Scientific Update Interim efficacy & pharmacodynamics data from a phase I trial in Solid tumours presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO-2011) [44] Updated 09 Jun 2011
06 Apr 2011 Scientific Update Pharmacodynamics data from preclinical trials in Solid tumours presented at the 102nd Annual Meeting of the American Association for Cancer Research (AACR-2011) [68] Updated 12 Apr 2011
16 Nov 2010 Scientific Update Pharmacodynamics data from preclinical trials in Solid tumours presented at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR-2010) [60] , [61] Updated 01 Dec 2010
16 Nov 2010 Scientific Update Interim efficacy, pharmacodynamics and pharmacokinetics data from a phase I trial in Solid tumours presented at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR-2010) [59] Updated 19 Nov 2010
20 Oct 2010 Company Involvement Cylene Pharmaceuticals and Horizon Discovery enter into a collaboration for the targeted development of CX 4945 [4] Updated 20 Oct 2010
09 Sep 2010 Trial Update Cylene Pharmaceuticals initiates enrolment in a phase I trial (NCT01199718) for Multiple myeloma in the US Updated 24 Sep 2010
21 Apr 2010 Scientific Update Pharmacodynamics & adverse events data from a phase I trial in Solid tumours presented at the 101st Annual Meeting of the American Association for Cancer Research (AACR-2010) [51] Updated 10 May 2010
19 Nov 2009 Scientific Update Pharmacodynamics data from a Preclinical trial in Breast cancer presented at the 21st AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (AACR-NCI-EORTC-2009) [62] Updated 21 Dec 2009
19 Nov 2009 Scientific Update Interim pharmacokinetics and adverse events data from a Phase-I trial in Solid tumours presented at the 21st AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (AACR-NCI-EORTC-2009) [52] Updated 19 Dec 2009
22 Apr 2009 Scientific Update Pharmacodynamics and pharmacokinetics data from preclinical trials in Cancer presented at the 100th Annual Meeting of the American Association for Cancer Research (AACR-2009) [64] , [63] , [65] Updated 04 May 2009
06 Jan 2009 Phase Change - I Phase-I clinical trials in Giant lymph node hyperplasia in USA (PO) Updated 06 Jan 2009
06 Jan 2009 Phase Change - I Phase-I clinical trials in late-stage Solid tumours in USA (PO) Updated 06 Jan 2009
06 Jan 2009 Phase Change - I Phase-I clinical trials in Multiple myeloma in USA (PO) Updated 06 Jan 2009

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  69. A Phase II, Randomized and Controlled Investigator Initiated Trial Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Outpatient Adult Subjects With Moderate Coronavirus Disease 2019 (COVID-19)

    ctiprofile
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