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 Date07 Nov 2022

Sponsor / Collaborator

Senhwa Biosciences, Inc.

NCT04890613 / RecruitingPhase 1

Phase Ib Expansion Study of CX-5461 in Patients With Solid Tumours and BRCA2 and/or PALB2 Mutation

This is an open-label, multi-center, phase 1b study designed to determine a tolerable dose of CX-5461 administered by IV infusion on Day 1 and Day 8 of a 28-day cycle in patients with selected solid tumours and associated mutations for future Phase II trials. The safety and tolerability of CX-5461, preliminary evidence of antitumor effect and the effect of CX-5461 on the Health-Related Quality of Life (HRQoL) will also be evaluated. The study will also evaluate the predictive value of mutational signatures and explore the significance of dynamic changes in ctDNA levels and plasma DNA methylome profiling in this study's exploratory cohort.

Start Date08 Sep 2021

Sponsor / Collaborator

Senhwa Biosciences, Inc.

100 Clinical Results associated with Senhwa Biosciences, Inc.

0 Patents (Medical) associated with Senhwa Biosciences, Inc.

Literatures (Medical) associated with Senhwa Biosciences, Inc.

01 Jan 2023·Neoplasia

A G-quadruplex stabilizer, CX-5461 combined with two immune checkpoint inhibitors enhances in vivo therapeutic efficacy by increasing PD-L1 expression in colorectal cancer

Article

Author: Su, Yeu ; Yeh, Chun-Nan ; Chang, Yu-Chan ; Hsu, Dennis Shin-Shian ; Soong, John ; Hung, Yi-Ping ; Hung, Ya-Chi ; Hsiao, Michael ; Chiang, Nai-Jung ; Lu, Meng-Lun ; Chen, Ming-Huang ; Chung, Shin-Yi

PURPOSEImmune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy can improve the limited efficacy of colorectal cancer (CRC) immunotherapy. CX-5461 causes substantial DNA damage and genomic instability and can increase ICIs' therapeutic efficacies through tumor microenvironment alteration.RESULTSWe analyzed whether CX-5461 enhances ICIs' effects in CRC and discovered that CX-5461 causes severe DNA damage, including cytosolic dsDNA appearance, in various human and mouse CRC cells. Our bioinformatics analysis predicted CX-5461-based interferon (IFN) signaling pathway activation in these cells, which was verified by the finding that CX-5461 induces IFN-α and IFN-β secretion in these cells. Next, cGAMP, phospho-IRF3, CCL5, and CXCL10 levels exhibited significant posttreatment increases in CRC cells, indicating that CX-5461 activates the cGAS-STING-IFN pathway. CX-5461 also enhanced PD-L1 expression through STAT1 activation. CX-5461 alone inhibited tumor growth and prolonged survival in mice. CX-5461+anti-PD-1 or anti-PD-L1 alone exhibited synergistic growth-suppressive effects against CRC and breast cancer. CX-5461 alone or CX-5461+anti-PD-1 increased cytotoxic T-cell numbers and reduced myeloid-derived suppressor cell numbers in mouse spleens.CONCLUSIONSTherefore, clinically, CX-5461 combined with ICIs for CRC therapy warrants consideration because CX-5461 can turn cold tumors into hot ones.

01 Jun 2022·Journal of Clinical Oncology

OZM-114: Phase Ib expansion study of CX-5461in patients with solid tumors and BRCA2 and/or PALB2 mutation.

Author: Bowering, Valerie ; Koziol, Kasia ; McMullen, Michelle ; Provencher, Diane M. ; McCormick, Daniel ; Chinta, Rishi ; Rosen, Lee S. ; Knox, Jennifer J. ; Huang, Chi-En ; Lheureux, Stephanie ; Alqaisi, Husam ; Oza, Amit M. ; Lee, Crystal ; Chang, Ariel ; Aguilar, Leslie ; Soong, John

TPS5621 Background: Pre-clinical and clinical data demonstrate that CX-5461 selectively kills HR deficient cancer cells through stabilizing G4 structures and inducing replication-dependent DNA damage. Phase 1 studies suggest CX-5461 has clinical activity and warrants further investigation in HR-deficient tumors, including those with pathogenic BRCA2 and PALB2 mutation. The recommended phase 2 dose (RP2D) requires further refinement to establish the chronic tolerable dose for further phase 2 trials, particularly regarding the incidence of ocular toxicity. The doses of 325mg/m2 and 250mg/m2 were selected for this study expansion cohorts because it is well within the efficacy range and below the first occurrence of ocular toxicity in a previous study. Methods: This is an open-label, multi-center, phase 1b study designed to determine a tolerable dose of CX-5461 in patients with ovarian, pancreatic, prostate, and breast cancers for Phase II trials. Eligible patients will be enrolled into two cohorts: A) Main cohort (target accrual: 32 patients) and B) Exploratory cohorts (target accrual: 20 patients), see table-1 below. The primary outcomes include assessment of: 1) Safety and tolerability of CX-5461, in particular to determine late onset ocular toxicity 2) Anti-tumor activity of CX-5461 in patients with solid tumors and germline BRCA2 and/or PALB2 mutation, and 3) Effect of CX-5461 on Quality of Life measures. Secondary outcomes include evaluation of :1) Safety: CTCAE v 5.0, SAEs, dose modifications due to AEs, 2) Activity: best overall response from tumor evaluations performed every 2 cycles, according to RECIST v1.1, and duration of response., and 3) patient-reported outcomes: PRO (PRO-CTCAE v1.0 questionnaires to evaluate cutaneous, gastrointestinal, visual/perceptual, cardio/circulatory, sleep/wake and miscellaneous symptoms. Exploratory Objectives include assessment of: 1) anti-tumor activity of CX-5461 in patients with ovarian cancer and pathogenic/likely-pathogenic BRCA1 mutation and/or other HRD-associated somatic mutation, and 2) molecular profile of tumors and predictive value of mutational signatures in predicting response or resistance to CX-5461. Clinical trial information: NCT04890613. [Table: see text]

01 Feb 2022·Journal of Clinical Oncology

Phase 1b expansion study of CX-5461 in patients with solid tumors and BRCA2 and/or PALB2 mutation.

Author: Oza, Amit M. ; Knox, Jennifer J. ; Chen, Jimmy ; Chen, Jenny ; Provencher, Diane M. ; Chang, Ariel ; Soong, John ; McCormick, Daniel

TPS622 Background: BRCA and PALB2 proteins play important roles in the maintenance of genomic stability as they are essential for error-free repair of double-stranded DNA breaks, while deficiency of these proteins promotes error-prone DNA repair, chromosomal instability and carcinogenesis. Inherited mutations in BRCA genes predispose to various early onset cancers. Poly(ADP-ribose) polymerase inhibitors (PARPi) inducing synthetic lethality in tumors with homologous recombination (HR)-mediated DNA repair deficiencies have been approved for treatment in patients with germline BRCA-mutated metastatic pancreatic adenocarcinoma. Unfortunately, resistance to PARPi associated with multiple mechanisms can be observed over time, suggesting a prominent unmet need for the development of new treatment options. CX-5461, a G-quadruplex stabilizer, employs an alternative mechanism in destabilizing the DNA replication fork to promote DNA damage resulting in cancer cell lethality in HR-deficient (HRD) tumors, thus represent a promising therapeutic strategy for patients with defects in HR-repair. Methods: A prior phase I dose escalation study has been completed for CX-5461 (CCTG IND.231, NCT02719977) but additional safety data are required to define the chronic tolerable dose for phase 2 trials. Therefore, a phase Ib expansion trial was designed for two doses preselected from our previous phase I trial to determine the final recommended phase II dose (RP2D) by evaluating safety, tolerability and objective response rate in a more selected population. This trial will enroll patients in two cohorts; the main cohort recruiting patients with pancreatic, breast, ovarian or prostate cancer with germline BRCA2 and/or PALB2 mutation, and an exploratory cohort recruiting ovarian cancer patients with BRCA1 and/or other HRD-associated mutations. Major eligibility criteria include documented evidence of pathogenic or likely pathogenic germline mutation in BRCA2 and/or PALB2 for main cohort patients, documented evidence of pathogenic or likely pathogenic germline mutation or a clinically actionable somatic mutation in BRCA1 and/or other HRD-associated mutation for exploratory cohort. Patients with non-adenocarcinoma histology of pancreatic cancer, known photosensitivity disorders of the skin, or patients with ophthalmological conditions will not be enrolled. An initial 16 eligible patients for the main cohort and 10 eligible patients for the exploratory cohort will be enrolled in parallel to receive CX-5461 at 250mg/m2, delivered via IV infusion on Day 1 and Day 8 of a 28-day cycle. Upon completion of the initial arms with no safety concerns, another two arms will open to enroll an additional 16 patients for the main cohort and 10 patients for the exploratory cohort to receive CX-5461 at 325mg/m2 of the same dosing schedule. Clinical trial information: NCT04890613.

News (Medical) associated with Senhwa Biosciences, Inc.

14 Oct 2024

·www.prnewswire.com

US FDA issues Study May Proceed letter for the Pilot Study of Pidnarulex Pharmacodynamics in Patients with Advanced Solid Tumors, Sponsored by the US National Cancer Institute

TAIPEI and SAN DIEGO, Oct. 14, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that FDA issues Study May Proceed letter for its developing drug Pidnarulex (CX-5461) in trial entitled "Pilot Study of Pidnarulex Pharmacodynamics in Patients with Advanced Solid Tumors" sponsored by the US National Cancer Institute (NCI). The study will assess whether Pidnarulex (CX-5461) induces a Rad51 response, in patients with and without homologous repair deficiency (HRD) genetic mutations. This pilot study also aims to explore potential biomarkers beyond BRCA1/2 and PALB2 that may demonstrate synthetic lethality with Pidnarulex (CX-5461). The findings from this study may identify patients who are more responsive to Pidnarulex (CX-5461) treatment, potentially expanding its therapeutic applications, and may accelerate its path to market approval. In addition to this monotherapy trial, the NCI is considering future clinical trials involving Pidnarulex (CX-5461) in combination with other therapies, such as immunotherapies and antibody-drug conjugates (ADCs). Should these trials proceed as planned, they will be led by the NCI, utilizing its vast medical expertise, scientific resources, and regulatory experience—support that could significantly accelerate the development of Pidnarulex. Pidnarulex (CX-5461), developed by Senhwa, is a first-in-class small-molecule designed to stabilize G-quadruplex (G4) structures, which are frequently observed in promoters of oncogenes. By stalling replication fork progression, Pidnarulex induces DNA damage and promotes cancer cell death. Through this mechanism, Pidnarulex holds great potential as a therapeutic agent for various cancers. In recent years, immunotherapy has been the fastest-growing category in the cancer drug market. According to the 2023 global best-selling drug market analysis, the first PD-1 inhibitor Keytruda(Pembrolizumab), developed by Merck, topped the sales charts with $25.11 billion. Immunotherapy and cancer drugs account for nearly half of the market sales. International clinical research indicates that combined immunotherapy can enhance tumor response rates, reduce mortality, and prolong patient survival. Given that only 20% to 25% of patients benefit from effective immunotherapy, Senhwa expects that in future immuno-combination therapy trials, CX-5461 will change the tumor microenvironment with its innovative mechanism, thereby enhancing the efficacy of immunotherapy, realizing the corporate mission of bringing hope to life. 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

ImmunotherapyClinical Study

18 Sep 2024

·www.prnewswire.com

Senhwa Biosciences Announces IND Submission to US FDA for Pilot Study of Pidnarulex Pharmacodynamics in Patients with Advanced Solid Tumors sponsored by NCI

TAIPEI and SAN DIEGO, Sept. 17, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), , a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that an Investigational New Drug (IND) application for Pidnarulex has been submitted to the U.S. FDA by the NCI. Senhwa' investigational drug, Pidnarulex (CX-5461), has been selected as an experimental drug in the NExT (NCI Experimental Therapeutics) cancer program, sponsored by the Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), for a five-year period. This drug will be used in a pharmacodynamic (PD) pilot study involving patients with advanced solid tumors. In addition to this monotherapy trial, NCI is considering to plan future clinical trials for Pidnarulex (CX-5461) in combination with other therapies, including immunotherapy, antibody-drug conjugates (ADC), and PARP inhibitors (Poly ADP-ribose Polymerase inhibitors, PARPi). Should these trials be realized, they will be led by the NCI, leveraging its medical team, scientific talent network, and regulatory resources—capabilities that most biotech companies would struggle to accomplish independently. This support from the NCI is hoped to significantly accelerate the development and expansion of indications for Pidnarulex (CX-5461), ultimately benefiting patients with an earlier market launch. This clinical trial, for which the IND application has been submitted by NCI's Division of Cancer Treatment and Diagnosis (DCTD), aims to explore the response of various biomarkers to Pidnarulex (CX-5461) in patients with or without homologous recombination deficiency (HRD). Pidnarulex (CX-5461), developed by Senhwa, is a first-in-class small-molecule designed to stabilize G-quadruplex (G4) structures, which are frequently observed in promoters of oncogenes. By stalling replication fork progression, Pidnarulex induces DNA damage and promotes cancer cell death. Through this mechanism, Pidnarulex holds great potential as a therapeutic agent for various cancers. In recent years, immunotherapy has become the fastest-growing category in the cancer drug market, while the development of antibody-drug conjugates (ADC) is undoubtedly an important trend in biopharmaceuticals. Major pharmaceutical companies, including Pfizer, AbbVie, AstraZeneca, and Merck, have invested billions of dollars in acquiring or licensing related technologies. According to a recent report from market research firm Evaluate, the ADC market is expected to reach $30 billion by 2028, while the global cancer immunotherapy market will surpass a staggering $224 billion by 2030. Given that only about 20% to 25% of patients are effectively treated with immunotherapy, combining immunotherapy with targeted drugs is becoming increasingly important in cancer treatment. Combination therapies can address multiple treatment pathways within the complex tumor microenvironment and may enhance the efficacy of immunotherapy, making it a hot research area for major pharmaceutical companies. Therefore, Senhwa is confident and optimistic about the NCI's plans to advance clinical trials of Pidnarulex (CX-5461) in combination with immunotherapy and ADCs. 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

ImmunotherapyINDADC

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 Senhwa Biosciences, Inc.

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Pipeline Snapshot as of 23 Dec 2024

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

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Drug(Targets)	Indications	Global Highest Phase

Silmitasertib ( CK2 )	Community Acquired Pneumonia More	Phase 2
Pidnarulex ( G4 )	Prostatic Cancer More	Phase 1
CX-8184 ( CK2 )	Infectious Lung Disorder More	Preclinical

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