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Silmitasertib - Senhwa Biosciences

Drug Profile

Silmitasertib - Senhwa Biosciences

Alternative Names: CX 4945

Latest Information Update: 03 Apr 2020

At a glance

  • Originator Cylene Pharmaceuticals
  • Developer Cylene Pharmaceuticals; Senhwa Biosciences; Stanford University School of Medicine
  • Class 3-ring heterocyclic compounds; Antineoplastics; 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
  • New Molecular Entity Yes

Highest Development Phases

  • Phase I/II Cholangiocarcinoma; Medulloblastoma
  • Phase I Basal cell cancer; Giant lymph node hyperplasia; Multiple myeloma; Solid tumours
  • Phase Unknown COVID 2019 infections

Most Recent Events

  • 31 Mar 2020 Investigation in COVID-2019 infections in Taiwan (PO)
  • 17 Apr 2019 Senhwa Biosciences and Pediatric Brain Tumor Consortium plans a phase I/II trial for Medulloblastoma in April 2019 in USA (PO, Capsule) (NCT03904862)
  • 01 Apr 2019 Phase-I clinical trials in Basal cell cancer (Metastatic disease, Second-line therapy or greater) in USA (PO) (NCT03897036)

Development Overview

Introduction

Silmitasertib, a first-in-class, orally-administered, small molecule inhibitor of casein kinase II (CK2), is being developed by Senhwa Biosciences for the treatment of cholangiocarcinoma, other solid tumours, including Castleman's disease (giant lymph node hyperplasia) and 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. Early stage clinical development in basal cell carcinoma, cholangiocarcinoma, giant lymph node hyperplasia, multiple myeloma and other solid tumours is underway in the US, South Korea and Taiwan. Clinical development for recurrent medulloblastoma is also underway in the US.

Senhwa Biosciences intends to explore the potential of silmitasertib as a therapeutic for COVID-2019 infections. Research revealed that inhibition of casein kinase II could potentially shift COVID-19's cellular environment into a more antiviral state. Casein kinase II disruption promotes the formation of stress granules, resulting in the inhibition of COVID-19 proliferation. Investigation is underway in Taiwan.

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

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. [2]

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 [3] . However it is unclear if Horizon are collaborating with Senhwa Biosciences.

Key Development Milestones

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 [4] .

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 [5] [6] .

In March 2019, Pediatric Brain Tumor Consortium in collaboration with St. Jude Children's Research Hospital and National Cancer Institute (NCI) inititated a phase I/II 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 will enrol approximately 60 participants in the US. The trial is also funded by NIH grant (No. 5UM1CA081457) [7] .

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 [2] .

In December 2016, the US FDA granted orphan drug designation to CX 4945 for the treatment of cholangiocarcinoma [2] [8] .

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. 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 [9] [10] [11] [12] [13] .

In November 2018, the US FDA approved IND application for silmitasertib, for the treatment of basal cell carcinoma [14] .

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) [15] [16] [17] .

As at September 2018, silmitasertib is still in phase I development in the US (Senhwa Biosciences pipeline, September 2018).

A dose-escalating, phase I trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral silmitasertib in patients with relapsed or refractory multiple myeloma was initiated in September 2010 (C4-09-001; NCT01199718). Approximately 22 patients from the US were enrolled [18] [19] .

In January 2009, a phase I trial in patients with advanced solid tumours, Castleman's disease, or multiple myeloma was initiated in the US (C4-08-001; NCT00891280). It aimed to determine the safety, tolerability, and pharmacokinetics of silmitasertib and to determine dosages for phase II trials. Patients received silmitasertib orally, twice daily [20] [21] . Interim results for 17 patients have been reported [22] [23] .

As at June 2018, Stanford University School of Medicine was conducting preclinical development in the treatment of recurrent medulloblastoma [2] .

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 [24] [25] [26] [27] .

Results from preclinical studies have been reported [28] [29] [30] [31] .

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 [32] .

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 [19] .

Drug Properties & Chemical Synopsis

  • Route of administration PO
  • Formulation Capsule, unspecified
  • Class 3-ring heterocyclic compounds, Antineoplastics, 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

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Basal cell cancer - Metastatic disease, Second-line therapy or greater Phase I USA PO / Capsule Senhwa Biosciences 01 Apr 2019
COVID 2019 infections - - Phase Unknown Taiwan PO / unspecified Senhwa Biosciences 31 Mar 2020
Cholangiocarcinoma - Combination therapy, First-line therapy Phase I/II South Korea, Taiwan, USA PO / Capsule Senhwa Biosciences 28 Jan 2015
Giant lymph node hyperplasia Castleman's disease Late-stage disease Phase I USA PO / Capsule Senhwa Biosciences 12 Sep 2018
Medulloblastoma - Recurrent, Second-line therapy or greater Phase I/II USA PO / Capsule Stanford University School of Medicine 18 Mar 2019
Multiple myeloma - Late-stage disease Phase I USA PO / Capsule Cylene Pharmaceuticals 12 Sep 2018
Solid tumours - Late-stage disease Phase I USA PO / Capsule Senhwa Biosciences 12 Sep 2018

Orphan Status

Indication Patient Segment Country Organisation Event Date
Cholangiocarcinoma - USA Senhwa Biosciences 04 Jan 2017

Commercial Information

Involved Organisations

Organisation Involvement Countries
Cylene Pharmaceuticals Originator USA
Senhwa Biosciences Owner Taiwan
Unknown Funder USA
National Cancer Institute (USA) Funder USA
Horizon Discovery Collaborator England
Pediatric Brain Tumor Consortium Collaborator USA
Stanford University School 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 [25] [22] [23] .

Preclinical

In preclinical studies, silmitasertib showed favourable pharmacokinetics and oral bioavailability in multiple species [31] .

Adverse Events

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 [23] . In further results for 17 patients in 5 dose cohorts (90, 160, 300, 460 and 700mg), no dose-limiting toxicities had been observed [22] . 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 [25] .

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 [25] [22] [15] .

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 [26] .

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 [33] .

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 [27] .

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 [28] .

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 [31] .

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 [30] .

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 [29] .

Therapeutic Trials

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 [15] . 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 [25] .

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) 09 Aug 2019

Development History

Event Date Update Type Comment
31 Mar 2020 Phase Change Investigation in COVID-2019 infections in Taiwan (PO) [4] 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 09 Aug 2019
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 USA (PO) (NCT03904862) Updated 09 Aug 2019
01 Nov 2018 Regulatory Status US FDA approves IND application for silmitasertib in Basal cell carcinoma [14] 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 [2] Updated 15 Jun 2018
12 Jun 2018 Phase Change - Preclinical Preclinical trials in Medulloblastoma (Recurrent) in USA (PO) [2] 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 [2] Updated 15 Jun 2018
01 Dec 2016 Regulatory Status Silmitasertib receives Orphan Drug status for Cholangiocarcinoma in USA [2] [8] 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 [10] 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 [11] 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
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) [15] 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) [33] 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) [26] , [27] 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) [25] 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 [3] 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) [22] 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) [28] 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) [23] 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) [30] , [29] , [31] 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

References

  1. Senhwa raises $17 million in series B.

    Media Release
  2. PBTC and Senhwa sign cooperation agreement to develop CX-4945 for pediatric brain tumor treatment.

    Media Release
  3. Horizon Discovery and Cylene Pharmaceuticals Collaborate in Rational Selection of Patients for Clinical Trials.

    Media Release
  4. Senhwa Biosciences Silmitasertib Named as Potential COVID-19 Therapy.

    Media Release
  5. Senhwa Biosciences Silmitasertib / Basal Cell Carcinoma Trial Completed 1st Patient Enrollment.

    Media Release
  6. A Phase I, Multi-Center, Open-Label, Treatment Duration Increment, Expansion, Safety, and Pharmacodynamic Study of CX-4945 Administered Orally Twice Daily to Patients With Advanced Basal Cell Carcinoma

    ctiprofile
  7. PBTC-053: A Pediatric Brain Tumor Consortium Phase I/ II and Surgical Study of CX-4945 in Patients With Recurrent SHH Medulloblastoma

    ctiprofile
  8. Senhwa Biosciences CX-4945 Granted Orphan Drug Designation by the US FDA in Cholangiocarcinoma.

    Media Release
  9. Senhwa CX-4945 Phase I Clinical Trial Results Accepted for Presentation at the 2017 ASCO Gastrointestinal Cancers Symposium.

    Media Release
  10. Senhwa Biosciences Receives TFDA's Permission to start Taiwan Phase 1/2 Trial of CX-4945 in Combination with Gemcitabine and Cisplatin.

    Media Release
  11. Senhwa Biosciences Receives Permission for Korean Phase 1/2 Trial of CX-4945 in Combination with Gemcitabine and Cisplatin.

    Media Release
  12. Senhwa Biosciences Initiates Phase 1/2 Trial of CX-4945 in Combination with Gemcitabine and Cisplatin.

    Media Release
  13. A Phase I/II Study of CX-4945 in Combination With Gemcitabine and Cisplatin in the Frontline Treatment of Patients With Cholangiocarcinoma

    ctiprofile
  14. Senhwa Biosciences Silmitasertib filed IND of Basal Cell Carcinoma approved by FDA.

    Media Release
  15. Cylene Presents Encouraging Clinical Data for Oral CK2 Inhibitor at ASCO.

    Media Release
  16. Phase II trial of CX 4945 in combination with erlotinib in patients with non-small cell lung cancer.

    ctiprofile
  17. Phase II trial of CX 4945 in combination with gemcitabine and carboplatin in patients with ovarian cancer.

    ctiprofile
  18. A Phase 1, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of CX-4945 Administered Orally to Patients With Relapsed or Refractory Multiple Myeloma.

    ctiprofile
  19. Cylene Initiates Phase I Trial in Multiple Myeloma With CX-4945 Inhibitor of CK2 and Closes Accompanying Financing.

    Media Release
  20. A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of CX-4945 Administered Orally to Patients With Advanced Solid Tumors, Castleman's Disease or Multiple Myeloma.

    ctiprofile
  21. Cylene Pharmaceuticals Initiates Phase I Trial With CX-4945 -Breakthrough First-in Class Inhibitor of CK2.

    Media Release
  22. Lim JKC, Padgett CS, Marschke RF, Northfelt DW, Andreopoulou E, Von Hoff DD, et al. Utility of clinical biomarkers for detecting protein kinase CK2 inhibition: A report from the phase I trial of CX-4945. 101st-AACR-2010 2010; abstr. 2763.

    Available from: URL: http://www.abstractsonline.com
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    Available from: URL: http://www.aacr.org/home/scientists/meetings--workshops/molecular-targets-and-cancer-therapeutics.aspx
  24. Cylene to Present Advances with Industry's Only Clinical CK2 Inhibitor, CX-4945, at EORTC-NCI-AACR.

    Media Release
  25. Padgett CS, Lim JKC, Marschke RF, Northfelt DW, Andreopoulou E, Von Hoff DD, et al. Clinical pharmacokinetics and pharmacodynamics of CX-4945, a novel inhibitor of protein kinase CK2: Interim report from the phase 1 clinical trial. 22nd-EORTC-NCI-AACR-2010 2010; abstr. 414.

    Available from: URL: http://www.ecco-org.eu
  26. Drygin D, Bliesath J, Siddiqui-Jain A, Huser N, Omori M, Streiner N, et al. Combined inhibition of EGFR and protein kinase CK2 synergistically blocks phosphorylation of ribosomal protein S6, induces apoptosis in cancer cells and displays enhanced antitumor activity in xenograft models. 22nd-EORTC-NCI-AACR-2010 2010; abstr. 99.

    Available from: URL: http://www.ecco-org.eu
  27. Anderes K, Bliesath J, Ho C, Omori M, Huser N, Siddiqui-Jain A, et al. CX-4945, an inhibitor of protein kinase CK2, disrupts DNA damage repair, potentiates apoptosis and enhances antitumor activity of gemcitabine in a model of ovarian cancer. 22nd-EORTC-NCI-AACR-2010 2010; abstr. 518.

    Available from: URL: http://www.ecco-org.eu
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    Available from: URL: http://www.aacr.org/home/scientists/meetings--workshops/molecular-targets-and-cancer-therapeutics.aspx
  29. Drygin D, Bliesath J, Ho C, Siddiqui-Jain A, Streiner N, Chua P, et al. CX-4945, a small molecule inhibitor of CK2, inhibits angiogenesis by affecting the vascular endothelium and suppressing hypoxia-activated Hif-1-alpha transcription. 100th-AACR-2009 2009; abstr. 145.

    Available from: URL: http://www.aacr.org
  30. Siddiqui-Jain A, Streiner N, Chua P, Pierre F, Omori M, O'Brien S, et al. CX-4945, a potent and selective inhibitor CK2, modulates Pl3K/AKT signaling and phosphorylation of p21 in vitro and in vivo: implications for biomarker development. 100th-AACR-2009 2009; abstr. 4768.

    Available from: URL: http://www.aacr.org
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    Available from: URL: http://www.aacr.org
  32. Senhwa Biosciences Raises $17M Series B.

    Media Release
  33. Bliesath J, Drygin D, Streiner N, Ho C, Siddiqui-Jain A, Proffitt C, et al. The CK2 inhibitor CX-4945 enhances the antitumor activity of EGFR-targeted agents by attenuating signaling in the PI3K/AKT/mTOR pathway. 102nd-AACR-2011 2011; abstr. 2560.

    Available from: URL: http://www.aacr.org
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