An Open Label, Intra-Subject Dose Escalation Study of CCX140-B in Subjects with Primary Focal Segmental Glomerulosclerosis (FSGS) and Nephrotic Syndrome

Start Date12 Oct 2019

Sponsor / Collaborator

ChemoCentryx, Inc.

NCT03703908 / TerminatedPhase 2

An Open Label, Intra-Subject Dose Escalation Study of CCX140-B in Subjects With Primary Focal Segmental Glomerulosclerosis (FSGS) and Nephrotic Syndrome

An Open Label, Intra-Subject Dose Escalation Study of CCX140 B in Subjects with Primary FSGS and Nephrotic Syndrome

Start Date01 Oct 2018

Sponsor / Collaborator

ChemoCentryx, Inc.

EUCTR2017-003021-15-PL / Not yet recruitingPhase 2

A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects with Focal Segmental Glomerulosclerosis (FSGS)

Start Date19 Jun 2018

Sponsor / Collaborator

ChemoCentryx, Inc.

100 Clinical Results associated with CCX-140

100 Translational Medicine associated with CCX-140

100 Patents (Medical) associated with CCX-140

Literatures (Medical) associated with CCX-140

01 Jun 2024·Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences

Computational Screening Using a Combination of Ligand-Based Machine Learning and Molecular Docking Methods for the Repurposing of Antivirals Targeting the SARS-CoV-2 Main Protease.

Article

Author: Hermawan, Adam ; Yuda, Gusti Putu Wahyunanda Crista ; Hanif, Naufa

BACKGROUND:

COVID-19 is an infectious disease caused by SARS-CoV-2, a close relative of SARS-CoV. Several studies have searched for COVID-19 therapies. The topics of these works ranged from vaccine discovery to natural products targeting the SARS-CoV-2 main protease (M^pro), a potential therapeutic target due to its essential role in replication and conserved sequences. However, published research on this target is limited, presenting an opportunity for drug discovery and development.

METHOD:

This study aims to repurpose 10692 drugs in DrugBank by using ligand-based virtual screening (LBVS) machine learning (ML) with Konstanz Information Miner (KNIME) to seek potential therapeutics based on M^pro inhibitors. The top candidate compounds, the native ligand (GC-376) of the M^pro inhibitor, and the positive control boceprevir were then subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) characterization, drug-likeness prediction, and molecular docking (MD). Protein-protein interaction (PPI) network analysis was added to provide accurate information about the M^pro regulatory network.

RESULTS:

This study identified 3,166 compound candidates inhibiting M^pro. The random forest (RF) molecular access system ML model provided the highest confidence score of 0.95 (bromo-7-nitroindazole) and identified the top 22 candidate compounds. Subjecting the 22 candidate compounds, the native ligand GC-376, and boceprevir to further ADMET property characterization and drug-likeness predictions revealed that one compound had two violations of Lipinski's rule. Additional MD results showed that only five compounds had more negative binding energies than the native ligand (- 12.25 kcal/mol). Among these compounds, CCX-140 exhibited the lowest score of - 13.64 kcal/mol. Through literature analysis, six compound classes with potential activity for M^pro were discovered. They included benzopyrazole, azole, pyrazolopyrimidine, carboxylic acids and derivatives, benzene and substituted derivatives, and diazine. Four pathologies were also discovered on the basis of the M^pro PPI network.

CONCLUSION:

Results demonstrated the efficiency of LBVS combined with MD. This combined strategy provided positive evidence showing that the top screened drugs, including CCX-140, which had the lowest MD score, can be reasonably advanced to the in vitro phase. This combined method may accelerate the discovery of therapies for novel or orphan diseases from existing drugs.

01 Jan 2022·The Journal of clinical endocrinology and metabolismQ2 · MEDICINE

Novel Therapies for Kidney Disease in People With Diabetes

Q2 · MEDICINE

Review

Author: Ekinci, Elif I ; MacIsaac, Richard J ; Coughlan, Melinda T ; Khurana, Nayana ; James, Steven

Abstract:

Context:

The increasing burden of diabetic kidney disease (DKD) has led to the discovery of novel therapies.

Objective:

This review aims to summarize the results of recent clinical trials that test the efficacy of potential therapies for DKD.

Methods:

A systematized narrative review was performed utilizing the PubMed, Embase (Ovid), CINAHL, and Cochrane databases (January 2010 to January 2021). The included trials assessed the efficacy of specific medications using renal endpoints in adult participants with type 1 or 2 diabetes.

Results:

Fifty-three trials were identified. Large, multinational, and high-powered trials investigating sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrated improved renal outcomes, even in patients with established DKD. Trials examining incretin-related therapies also showed some improvement in renal outcomes. Additionally, mineralocorticoid receptor antagonists exhibited potential with multiple improved renal outcomes in large trials, including those involving participants with established DKD. Atrasentan, baricitinib, ASP8232, PF-04634817, CCX140-B, atorvastatin, fenofibrate, probucol, doxycycline, vitamin D, omega-3 fatty acids, silymarin, turmeric, total glucosides of paeony, and tripterygium wilfordii Hook F extract were all associated with some improved renal endpoints but need further exploration. While bardoxolone methyl was associated with a decrease in albuminuria, high rates of cardiovascular adverse effects curtailed further exploration into this agent. Selonsertib, allopurinol, praliciguat, palosuran, benfotiamine, and diacerein were not associated with improved renal outcomes.

Conclusion:

Trials have yielded promising results in the search for new therapies to manage DKD. SGLT2 inhibitors and incretin-related therapies have demonstrated benefit and were associated with improved cardiovascular outcomes. Mineralocorticoid receptor antagonists are another class of agents with increasing evidence of benefits.

01 Sep 2015·The lancet. Diabetes & endocrinologyQ1 · MEDICINE

The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial

Q1 · MEDICINE

Article

Author: Bekker, Pirow ; Hasslacher, Christopher ; Henkel, Elena ; Gouni-Berthold, Ioanna ; Potarca, Antonia ; Mehling, Heidrun ; Schall, Thomas J ; de Zeeuw, Dick ; Tesar, Vladimir ; Heerspink, Hiddo J Lambers

BACKGROUND:

Patients with type 2 diabetes and nephropathy have high cardiorenal morbidity and mortality despite optimum treatment including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Residual risk is related to residual albuminuria. We assessed whether CCX140-B, a selective inhibitor of C-C chemokine receptor type 2 (CCR2), could further reduce albuminuria when given in addition to standard care, including ACE inhibitors or ARBs.

METHODS:

In this randomised, double-blind, placebo-controlled clinical trial, we recruited patients from 78 research centres in Belgium, Czech Republic, Germany, Hungary, Poland, and the UK. We enrolled patients with type 2 diabetes aged 18-75 years with proteinuria (first morning void urinary albumin to creatinine ratio [UACR] 100-3000 mg/g), estimated glomerular filtration rate of 25 mL/min per 1·73 m(2) or higher, and taking stable antidiabetic treatment and ACE inhibitors or ARBs, for at least 8 weeks before study entry. Patients were stratified based on baseline UACR and renal function (estimated glomerular filtration rate), and then randomly assigned (1:1:1) via an interactive web response system with a minimisation algorithm to oral placebo, 5 mg CCX140-B, or 10 mg CCX140-B once a day. The 12-week dosing period in the initial protocol was extended to 52 weeks by protocol amendment. The primary efficacy measure was change from baseline in UACR during 52 weeks in the modified intention-to-treat population (all patients with uninterrupted dosing, excluding patients who stopped dosing at week 12 either permanently under the original protocol, or temporarily because of delay in approval of the protocol amendment). We did safety analyses on all randomly assigned patients who received at least one dose of study drug. According to a prespecified analysis plan, we analysed the primary endpoint with one-sided statistical testing with calculation of upper 95% confidence limits of the differences between active and control. This trial is registered with ClinicalTrials.gov, number NCT01447147.

FINDINGS:

The study ran from Dec 7, 2011 (first patient enrolled), until Aug 4, 2014. We enrolled 332 patients: 111 were assigned to receive placebo, 110 to 5 mg CCX140-B, and 111 to 10 mg CCX140-B. Of these, 192 were included in the modified intention-to-treat population. UACR changes from baseline during 52 weeks were -2% for placebo (95% CI -11% to 9%), -18% for 5 mg CCX140-B (-26% to -8%), and -11% for 10 mg CCX140-B (-20% to -1%). We recorded a -16% difference between 5 mg CCX140-B and placebo (one-sided upper 95% confidence limit -5%; p=0·01) and a -10% difference between 10 mg CCX140-B and placebo (upper 95% confidence limit 2%; p=0·08). Adverse events occurred in 81 (73%) of 111 patients in the placebo group versus 71 (65%) of 110 patients in the CCX140-B 5 mg group and 68 (61%) of 111 patients in the CCX140-B 10 mg group; there were no renal events during the study.

INTERPRETATION:

Our data suggest that CCR2 inhibition with CCX140-B has renoprotective effects on top of current standard of care in patients with type 2 diabetes and nephropathy.

FUNDING:

ChemoCentryx.

News (Medical) associated with CCX-140

29 Apr 2021

·www.globenewswire.com

ChemoCentryx Reports First Quarter 2021 Financial Results

-- Applications for regulatory approval of avacopan in ANCA-associated vasculitis under review in the United States, Europe and Japan; PDUFA goal date of July 7, 2021, with Advisory Committee scheduled for May 6 -- -- Novel orally administered checkpoint inhibitor CCX559 featured at American Association for Cancer Research Annual Meeting, expected to enter clinical development as a next generation cancer treatment in Q2 2021 -- -- Other avacopan programs: severe Hidradenitis Suppurativa (HS) Phase III and Lupus Nephritis development initiation on track for 2H 2021 -- -- $424 million in cash and investments at March 31, 2021 -- -- Conference call today at 5:00 p.m. Eastern Time -- SAN CARLOS, Calif., April 29, 2021 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc., (Nasdaq: CCXI), today announced financial results for the first quarter ended March 31, 2021 and provided an overview of recent corporate highlights. "Momentum builds with each passing quarter, bringing us closer to our goal of bringing novel, precisely targeted medicine to those that need it most,” said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. “At our R&D Day earlier this month, two world-renowned clinicians outlined the unmet needs in ANCA-associated vasculitis and the data driving their conviction that avacopan could become a landscape-changing therapy. We are well prepared and look forward to providing our views at the FDA Advisory Committee meeting on this topic in just a few days. During our R&D Day we also took the opportunity to establish how our novel small molecule PD-1/PD-L1 inhibitor CCX559 could transcend current limitations in the treatment of cancer. Meanwhile we are progressing toward our next cycle of clinical trials: a Phase III trial of avacopan in patients with severe HS; the initiation of clinical development of avacopan in lupus nephritis, and our first in human studies of the novel orally administered checkpoint inhibitor CCX559 in cancer patients. We look forward to an historic year of 2021 at ChemoCentryx, and we will devote all our energies to making the dream of breakthrough new therapies a reality for patients.” Key First Quarter 2021 Highlights and Recent Developments First Quarter 2021 Financial Results Revenue was $10.4 million for the first quarter of 2021, compared to $6.0 million for the same period in 2020. The increase in revenue from 2020 to 2021 was principally attributable to the $10.0 million milestone from Vifor for the February 2021 acceptance of the Japanese NDA for avacopan in the treatment of ANCA vasculitis. Research and development expenses were $23.4 million for the first quarter of 2021, compared to $19.3 million for the same period in 2020. The increase from 2020 to 2021 was primarily attributable to the manufacture of commercial drug supply in anticipation of the launch of avacopan for the treatment of ANCA vasculitis and costs associated with the advancement of CCX559, the Company’s orally-available small molecule checkpoint (PD-1/PD-L1) inhibitor. These increases were partially offset by lower Phase II related expenses due to the completion of patient enrollment of the avacopan AURORA Phase IIb clinical trial in patients with HS and the discontinuation of further clinical development of CCX140 in FSGS in 2020. General and administrative expenses were $16.3 million for the first quarter of 2021, compared to $8.8 million for the same period in 2020. The increase from 2020 to 2021 was primarily due to higher employee-related expenses, including those associated with the Company’s commercialization planning efforts, and higher professional fees. Net loss for the first quarter of 2021 was $29.7 million, compared to net loss of $21.7 million for the same period in 2020. Total shares outstanding at March 31, 2021 were approximately 69.7 million shares. Cash, cash equivalents and investments totaled $424.2 million at March 31, 2021. The Company expects to utilize cash, cash equivalents and investments in the range of $145 million to $155 million in 2021. Conference Call and Webcast The Company will host a conference call and webcast today, April 29, 2021 at 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time. To participate by telephone, please dial (877) 303-8028 (Domestic) or (760) 536-5167 (International). The conference ID number is 3963565. A live and archived audio webcast can be accessed through the Investors section of the Company's website at . The archived webcast will remain available on the Company's website for fourteen (14) days following the call. About ChemoCentryx ChemoCentryx is a biopharmaceutical company developing new medications for inflammatory and autoimmune diseases and cancer. ChemoCentryx targets the chemokine and chemoattractant systems to discover, develop and commercialize orally administered therapies. ChemoCentryx’s lead drug candidate, avacopan (CCX168), successfully completed a pivotal Phase III trial in ANCA-associated vasculitis and a New Drug Application is under review by the U.S. Food and Drug Administration. Avacopan is also in late stage clinical development for the treatment of severe Hidradenitis Suppurativa and C3 glomerulopathy (C3G). ChemoCentryx also has early stage drug candidates that target chemoattractant receptors in other inflammatory and autoimmune diseases and in cancer. Forward-Looking StatementsChemoCentryx cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "may," "could," "will," "would," "should," "expect," "plan," "anticipate," "believe," "estimate," "intend," "predict," "seek," "contemplate," "potential," "continue" or "project" or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include the Company's statements regarding the achievement of anticipated goals and milestones, whether avacopan will be approved by the FDA, EMA or PMDA for the treatment of ANCA-associated vasculitis, the timing of the FDA’s, EMA’s and PMDA’s decision on the NDA, MAA, and JNDA, respectively, the timing of the potential commercial launch of avacopan in ANCA-associated vasculitis, whether avacopan will be an effective treatment in other indications such as severe HS, C3G and lupus nephritis, whether a Phase III trial of avacopan in patients with severe HS will commence in Q4 2021, whether avacopan for lupus nephritis and CCX559 will enter clinical trials in 2021 in Q4 2021 and Q2 2021, respectively, whether actual cash utilization will fall within projections and whether the Company's drug candidates will be shown to be effective in ongoing or future clinical trials. The inclusion of forward-looking statements should not be regarded as a representation by ChemoCentryx that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in the ChemoCentryx business and other risks described in the Company's filings with the Securities and Exchange Commission ("SEC"). Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and ChemoCentryx undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in ChemoCentryx's periodic reports filed with the SEC, including ChemoCentryx's Annual Report on Form 10-K filed with the SEC on March 1, 2021 and its other reports which are available from the SEC's website () and on ChemoCentryx's website () under the heading "Investors." All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995. Contacts:Susan M. KanayaExecutive Vice President,Chief Financial and Administrative Officerinvestor@chemocentryx.com Media:Stephanie Tomei408.234.1279media@chemocentryx.com Investors:Burns McClellanLee Roth212.213.0006 lroth@burnsmc.com

Small molecular drugFinancial StatementAACR

20 Mar 2018

·www.bioportfolio.com

ChemoCentryx Inc CCXI Pharmaceuticals Healthcare Deals and Alliances Profile [Report Updated: 27022018] Prices from USD $250

Summary ChemoCentryx Inc ChemoCentryx is a biopharmaceutical company that discovers, develops and commercializes orallyadministered therapeutics for the treatment of cancer, autoimmune diseases, and inflammatory disorders. The company's pipeline products include C5aR programs, CCR2 program, CCR9 program, and CCR1 program. ChemoCentryx's C5aR Program is for the treatment of antineutrophil cytoplasmic antibody associated renal vasculitis. The company's CCR2 Program provides CCX140 for the treatment of diabetic nephropathy, a form of kidney disease and CCX872 for the treatment of pancreatic cancer. Its CCR9 Program is for the treatment of patients with Crohn's disease and CCX507 is for the treatment of inflammatory bowel disease. ChemoCentryx is headquartered in Mountain View, California, the US. ChemoCentryx Inc CCXI Pharmaceuticals Healthcare Deals and Alliances Profile provides you comprehensive data and trend analysis of the company's Mergers and Acquisitions MAs, partnerships and financings. The report provides detailed information on Mergers and Acquisitions, Equity/Debt Offerings, Private Equity, Venture Financing and Partnership transactions recorded by the company over a five year period. The report offers detailed comparative data on the number of deals and their value categorized into deal types, subsector and regions. GlobalData derived the data presented in this report from proprietary inhouse Pharma eTrack deals database, and primary and secondary research. Scope Financial Deals Analysis of the company's financial deals including Mergers and Acquisitions, Equity/Debt Offerings, Private Equity, Venture Financing and Partnerships. Deals by Year Chart and table displaying information encompassing the number of deals and value reported by the company by year, for a five year period. Deals by Type Chart and table depicting information including the number of deals and value reported by the company by type such as Mergers and Acquisitions, Equity/Debt Offering etc. Deals by Region Chart and table presenting information on the number of deals and value reported by the company by region, which includes North America, Europe, Asia Pacific, the Middle East and Africa and South and Central America. Deals by Subsector Chart and table showing information on the number of deals and value reported by the company, by subsector. Major Deals Information on the company's major financial deals. Each such deal has a brief summary, deal type, deal rationale; and deal financials and target Company's major public companies key financial metrics and ratios. Business Description A brief description of the company's operations. Key Employees A list of the key executives of the company. Important Locations and Subsidiaries A list and contact details of key centers of operation and subsidiaries of the company. Key Competitors A list of the key competitors of the company. Key Recent Developments A brief on recent news about the company. Reasons to Buy Get detailed information on the company's financial deals that enable you to understand the company's expansion/divestiture and fund requirements The profile enables you to analyze the company's financial deals by region, by year, by business segments and by type, for a five year period. Understand the company's business segments' expansion / divestiture strategy The profile presents deals from the company's core business segments' perspective to help you understand its corporate strategy. Access elaborate information on the company's recent financial deals that enable you to understand the key deals which have shaped the company Detailed information on major recent deals includes a summary of each deal, deal type, deal rationale, deal financials and Target Company's key financial metrics and ratios. Equip yourself with detailed information about the company's operations to identify potential customers and suppliers. The profile analyzes the company's business structure, locations and subsidiaries, key executives and key competitors. Stay uptodate on the major developments affecting the company Recent developments concerning the company presented in the profile help you track important events. Gain key insights into the company for academic or business research Key elements such as break up of deals into categories and information on detailed major deals are incorporated into the profile to assist your academic or business research needs. Note*: Some sections may be missing if data is unavailable for the company.

AntibodyAcquisition

100 Deals associated with CCX-140

External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Nephrotic Syndrome	Phase 2	US	ChemoCentryx, Inc.	01 Oct 2018
Glomerulosclerosis, Focal Segmental	Phase 2	US	ChemoCentryx, Inc.	17 May 2018
Glomerulosclerosis, Focal Segmental	Phase 2	AU	ChemoCentryx, Inc.	17 May 2018
Glomerulosclerosis, Focal Segmental	Phase 2	CA	ChemoCentryx, Inc.	17 May 2018
Glomerulosclerosis, Focal Segmental	Phase 2	FR	ChemoCentryx, Inc.	17 May 2018
Glomerulosclerosis, Focal Segmental	Phase 2	IT	ChemoCentryx, Inc.	17 May 2018
Glomerulosclerosis, Focal Segmental	Phase 2	NZ	ChemoCentryx, Inc.	17 May 2018
Glomerulosclerosis, Focal Segmental	Phase 2	PL	ChemoCentryx, Inc.	17 May 2018
Glomerulosclerosis, Focal Segmental	Phase 2	GB	ChemoCentryx, Inc.	17 May 2018
Albuminuria	Phase 2	NL	ChemoCentryx, Inc.	01 Sep 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03703908 (CTgov)	Phase 2	Glomerulosclerosis, Focal Segmental \| Nephrotic Syndrome	5	CCX140-B	vbmzhzpyvx(hehfwoyydv) = kkfrrvskpb wlzduzvmnr (qzgxgczsxe, ktzgmnodnx - iiwzbmfhcu) View more	-	06 Feb 2024
NCT03536754 (LUMINA-1, BusinessWire) Manual	Phase 2	Glomerulosclerosis, Focal Segmental	46	CCX-140	lynaymmawp(ryfjbgcdhs) = none during the blinded trial behdwmhzlb (qdneydcsce ) View more	Negative	18 May 2020
NCT03536754 (LUMINA-1, BusinessWire) Manual	Phase 2	Glomerulosclerosis, Focal Segmental	46	Placebo		Negative	18 May 2020

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