Delving into the Latest Updates on BMS-813160 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BMS 813160

Target

CCR2 x CCR5

Action

antagonists

Mechanism

CCR2 antagonists(C-C chemokine receptor type 2 antagonists), CCR5 antagonists(C-C chemokine receptor type 5 antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Hepatocellular CarcinomaNon-Small Cell Lung CancerAdvanced Pancreatic Ductal Adenocarcinoma+ [1]

Inactive Indication

Advanced cancerAdvanced Malignant Solid NeoplasmAdvanced Renal Cell Carcinoma+ [5]

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol Myers Squibb Co.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H40N8O2

InChIKeyCMVHFGNTABZQJU-HCXYKTFWSA-N

CAS Registry1286279-29-5

The purpose of this research study is to study the effect of giving nivolumab with CCR2/5-inhibitor or anti-IL-8 before surgery, and after surgery, with the goal of determining if this medicine results in:
1. A significant immune response against their tumor (which the study team will see in the tumor that is taken out at the time of surgery)
2. Improvement in long term survival rates

Start Date05 Mar 2020

Sponsor / Collaborator

Icahn School of Medicine at Mount Sinai

[+1]

NCT03767582

/ CompletedPhase 1/2IIT

A Phase I/II Trial of Combination Immunotherapy With Nivolumab and a CCR2/CCR5 Dual Antagonist (BMS-813160) With or Without GVAX Following Chemotherapy and Radiotherapy for Locally Advanced Pancreatic Ductal Adenocarcinomas (PDACs).

The purpose of this study is to evaluate if the combination of nivolumab and a CCR2/CCR5 dual antagonist (BMS-813160) with GVAX is safe in patients with locally advanced pancreatic cancer (LAPC) who have received chemotherapy and radiotherapy, and to see if this combination therapy enhances the infiltration of CD8+CD137+ cells in PDACs .

Start Date12 Dec 2019

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

[+1]

NCT03496662

/ CompletedPhase 1/2IIT

A Phase I/II Study to Evaluate the Tolerability and Efficacy of BMS-813160 (CCR2/5 Inhibitor) With Nivolumab and Gemcitabine and Nab-paclitaxel in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC)

The purpose of this research study is to learn more about a new combination of drugs being given to treat pancreatic cancer. The drugs being tested are BMS-813160, nivolumab, gemcitabine, and nab-paclitaxel. The investigators will be looking at both the side effects and the way the disease responds to treatment.

Start Date31 Aug 2018

Sponsor / Collaborator

Washington University School of Medicine

[+4]

100 Clinical Results associated with BMS-813160

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100 Translational Medicine associated with BMS-813160

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100 Patents (Medical) associated with BMS-813160

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9

Literatures (Medical) associated with BMS-813160

01 Jan 2026·Journal for ImmunoTherapy of Cancer

Phase 1b/2 study of BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy or nivolumab in patients with advanced pancreatic or colorectal cancer

Article

Author: BasuMallick, Atrayee ; Ma, Wen Wee ; Twyman Saint Victor, Christina ; Garrido-Laguna, Ignacio ; Davis, S Lindsey ; Gutierrez, Martin ; O’Brien, Shaun ; Folprecht, Gunnar ; Osawa, Mayu ; Dutta, Santanu ; Xu, Ke ; Chen, Eric ; Lenz, Heinz-Josef ; Le, Dung T ; Novosiadly, Ruslan D ; Varghese, Anna M ; Greenawalt, Danielle M ; Noel, Marcus ; Dayyani, Farshid ; Trikalinos, Nikolaos A

Background:

Cysteine–cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.

Methods:

Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once daily, or 150 mg once daily) and then BMS-813160+chemotherapy (gemcitabine+nab-paclitaxel (gem/nabP; 1L PDAC), 5-fluorouracil+leucovorin+irinotecan (FOLFIRI; 1L CRC)), or nivolumab (2/3L MSS CRC).Part 2 included patients with metastatic 1L PDAC or 2L CRC. Patients received BMS-813160 300 mg two times a day+gem/nabP±nivolumab (1L PDAC), BMS-813160 300 mg two times a day or 150 mg once daily+FOLFIRI (2L CRC), or chemotherapy alone. Primary endpoints were safety and pharmacodynamics (Part 1) and efficacy (Part 2).

Results:

In Part 1, 22 of 75 (29%) and 54 of 72 (72%) patients experienced a treatment-related adverse event during monotherapy lead-in and overall, respectively. Two dose-limiting toxicities (rash and pericardial effusion with pericarditis, both grade 3) occurred. In Part 2, patients with 1L PDAC who received BMS-813160 300 mg two times a day+gem/nabP+nivolumab achieved an overall response rate (ORR) of 37% (13/35); the median duration of response (DOR) was 45 weeks (95% CI 26.1 to not evaluable). ORRs with BMS-813160 300 mg two times a day+gem/nabP and gem/nabP alone were 26% (9/35) and 28% (9/32), respectively; median DORs were 121 and 31 weeks, respectively. Progression-free survival rates at 24 weeks were 56% (BMS-813160 300 mg two times a day+gem/nabP+nivolumab), 56% (BMS-813160 300 mg two times a day+gem/nabP), and 50% (gem/nabP). ORRs in 2L CRC were 19% (6/32; BMS-813160 300 mg two times a day+FOLFIRI), 13% (4/32; BMS-813160 150 mg once daily+FOLFIRI), and 27% (7/26; FOLFIRI).

Conclusions:

In 1L PDAC, BMS-813160 300 two times a day+gem/nabP±nivolumab demonstrated durable antitumor response and was well tolerated. BMS-813160 combination regimens were tolerable in other cohorts, but clinical efficacy was not demonstrated.

Trial registration number:

NCT03184870 .

01 Nov 2022·TETRAHEDRON LETTERS

An azirine solid-state photodegradant of the CCR2/CCR5 dual antagonist BMS-813160

Author: Zang, Jia ; Fenster, Michael D. B. ; Hritzko, Benjamin ; Yuill, Elizabeth M. ; La Cruz, Thomas ; Sarjeant, Amy ; Ayers, Sloan ; Lin, Ziqing ; Park, Hyunsoo ; Huang, Yande ; Zaretsky, Serge ; Ramirez, Antonio

The synthesis of the CCR2/5 dual chemokine antagonist BMS-813160 (1) presented a number of interesting impurity and degradant structure elucidation challenges.This publication will focus on the structure elucidation of the solid-state photodegradant of 1 which produced an unexpected stable azirine species.The structure was elucidated by mass spectrometry and NMR, with confirmation by single-crystal X-ray crystallog.

18 Feb 2022·The Journal of organic chemistryQ2 · CHEMISTRY

Scalable Asymmetric Synthesis of the All Cis Triamino Cyclohexane Core of BMS-813160

Q2 · CHEMISTRY

Article

Author: Kay A. Galindo ; Charles Pathirana ; Yi Xiao ; Nathaniel Kopp ; Michael A. Galella ; Joerg Deerberg ; Bin Zheng ; Francisco González-Bobes ; Martin D. Eastgate ; Yu Fan ; Thomas E. La Cruz ; Chris Sfouggatakis

BMS-813160 is a pharmaceutical entity currently in development at Bristol Myers Squibb. Its defining structural feature is a unique chiral all cis triamino cyclohexane core. Medicinal and process chemistry groups at BMS have previously published synthesis strategies for chemotypes similar to the target molecule, but a streamlined approach amenable for longer-term supply was necessary. A new synthetic route was conceptualized, experimentally investigated, and determined to meet the criteria for efficiency that addressed key limitations of previous approaches. Adopting/optimizing the Trost asymmetric allylic amination desymmetrization methodology was a key tool used to produce a synthesis intermediate with high optical purity. In addition, developing a tandem Mannich-aza-Michael reaction to obviate the need for a Curtis/acylation sequence and a novel reductive amination/thermal lactamization to circumvent Freidinger-type pyrrolidone preparation are some of the synthesis improvements that enabled access to the target molecule to fulfill long-term supply requirements.

1

News (Medical) associated with BMS-813160

08 May 2023

·www.prnewswire.com

Global Pancreatic Cancer Competitive Landscape Report 2023: Comprehensive Insights about 250+ Companies and 300+ Drugs

DUBLIN, May 8, 2023 /PRNewswire/ -- The "Pancreatic Cancer - Competitive landscape, 2023" report has been added to ResearchAndMarkets.com's offering. This "Pancreatic Cancer- Competitive landscape, 2023" report provides comprehensive insights about 250+ companies and 300+ drugs in Pancreatic Cancer Competitive landscape. It covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. In March 2023, Adaptimmune Therapeutics plc. and TCR Therapeutics Inc. (NASDAQ: TCRR), announced entry into a definitive agreement under which Adaptimmune will combine with TCR in an all-stock transaction to create a preeminent cell therapy company focused on treating solid tumors. The combination provides extensive benefits for clinical development and product delivery supported by complementary technology platforms. As a result, and following the closing of the transaction, it is anticipated that the combined company's cash runway will extend into 2026. In February 2023, Akamis Bio, announced an expansion of its ongoing partnership with the Parker Institute for Cancer Immunotherapy (PICI) to include a clinical collaboration with the Cancer Research Institute (CRI) that will focus on advancing novel treatments for pancreatic cancer. As part of the Akamis Bio, PICI, and CRI partnership, NG-350A, an immuno-stimulatory tumor gene therapy driving intratumoral expression of a CD40 agonist monoclonal antibody, will be evaluated in combination with standard-of-care chemotherapy and the CTLA-4 inhibitor ipilimumab (YERVOY). In February 2023, Gritstone bio, Inc. announced that it has entered into a clinical trial agreement with the National Cancer Institute (NCI), an institute of the National Institutes of Health, to evaluate an autologous T cell therapy expressing a T cell receptor targeting mutated KRAS in combination with Gritstone's KRAS-directed vaccine candidate, SLATE-KRAS, in a Phase 1 study. Under the terms of the agreement, NCI will identify patients with metastatic cancer that are eligible for adoptive cell transfer based on the presence of a G12V or G12D KRAS mutation (KRASmut). In February 2023, Keymed Biosciences Inc., jointly announced a global exclusive license agreement with AstraZeneca for CMG901, a potential first-in-class Claudin 18.2 antibody drug conjugate (ADC). Under the license agreement, AstraZeneca will be responsible for the research, development, manufacture and commercialization of CMG901 globally. CMG901 is currently in a Phase I clinical trial for the treatment of Claudin 18.2-positive solid tumors. In January 2023, AIM ImmunoTech Inc. announced it has entered into an external sponsored collaborative clinical research agreement with Erasmus MC and AstraZeneca. Under the agreement, Erasmus MC is planning to perform an investigator-initiated clinical study, entitled "Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy effect. DURIPANC Study," in which it will use both Study Drugs provided by AstraZeneca and AIM ImmunoTech. Pancreatic Cancer Analytical Perspective In-depth Commercial Assessment: Pancreatic Cancer Collaboration Analysis by Companies The Report provides in-depth commercial assessment of drugs that have been included, which comprises collaboration, agreement, licensing and acquisition - deals values trends. The sub-segmentation is described in the report which provide company-company collaboration (licensing/partnering), company academic collaboration and acquisition analysis in tabulated form. Key Questions Answered Current Treatment Scenario and Emerging Therapies: How many companies are developing Pancreatic Cancer drugs? How many Pancreatic Cancer drugs are developed by each company? How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Pancreatic Cancer? What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Pancreatic Cancer therapeutics? What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies? What are the clinical studies going on for Pancreatic Cancer and their status? What are the key designations that have been granted to the emerging and approved drugs? Key Players Panbela Therapeutics ERYtech Pharma Jiangsu HengRui Medicine Co., Ltd. FibroGen Novartis AG AB Science TME Pharma AG Intensity Therapeutics Silenseed LTD SynerGene Therapeutics Elevation oncology Salspera LLC Redx Pharma Plc AIM ImmunoTech Inc. Rain Oncology Jazz Pharmaceuticals Invyte Corporation Immodulon Therapeutics Ltd GSK plc Merck Sharp & Dohme LLC Roche Helsinn Healthcare SA Argenus Inc. Actuate Therapeutics OSE Immunotherapeutics Incyte Corporation Galera Therapeutics CSPC ZhongQi Pharmaceutical Technology Astellas Pharma Global Development, Inc. NanOlogy Theriva Biologics AstraZeneca Berg, LLC Agenus ABVC BioPharma, Inc. Boehringer Ingelheim Alligator Bioscience CARsgenTherapeutics Co.,Ltd Purple Biotech Ltd. Lisata Therapeutics Chongqing Precision Biotech Co., Ltd Cybrexa Therapeutics Bold Therapeutics BioNTech SE Bristol-Myers Squibb DEKA Biosciences Senhwa Biosciences Cue Biopharma Carisma Therapeutics Inc Key Products Olaptesed pegol INT230-6 SBP-101 Masitinib NIS793 siG12D LODER SGT-53 Seribantumab Salmonella-IL2 RXC004 Rintatolimod RAIN-32 Lurbinectedin Retifanlimab IMM-101 GSK2256098 Belzutifan Atezolizumab Anamorelin AGEN1423 Elraglusib OSE2101 Epacadostat GC4711 Docetaxel Zolbetuximab NanoPac VCN-01 Danvatirsen BPM31510 Botensilimab ABV-1703 BI 907828 Mitazalimab CT041 CM24 CEND-1 CEA-targeted CAR-T cells CBX-12 BOLD-100 BNT141 BMS-813160 DK210 CX-5461 CUE-102 CT-0508 For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

ImmunotherapyLicense out/inVaccinePhase 1ADC

100 Deals associated with BMS-813160

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16240

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Phase 2	United States	Bristol Myers Squibb Co.	05 Mar 2020
Non-Small Cell Lung Cancer	Phase 2	United States	Bristol Myers Squibb Co.	05 Mar 2020
Advanced Pancreatic Ductal Adenocarcinoma	Phase 2	United States	Bristol Myers Squibb Co.	12 Dec 2019
Locally Advanced Pancreatic Adenocarcinoma	Phase 2	United States	Bristol Myers Squibb Co.	12 Dec 2019
Advanced Malignant Solid Neoplasm	Phase 2	United States	Bristol Myers Squibb Co.	08 Aug 2017
Advanced Malignant Solid Neoplasm	Phase 2	Australia	Bristol Myers Squibb Co.	08 Aug 2017
Advanced Malignant Solid Neoplasm	Phase 2	Belgium	Bristol Myers Squibb Co.	08 Aug 2017
Advanced Malignant Solid Neoplasm	Phase 2	Canada	Bristol Myers Squibb Co.	08 Aug 2017
Advanced Malignant Solid Neoplasm	Phase 2	Germany	Bristol Myers Squibb Co.	08 Aug 2017
Advanced Malignant Solid Neoplasm	Phase 2	Spain	Bristol Myers Squibb Co.	08 Aug 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03184870 (Pubmed \| J Immunother Cancer)	Phase 1/2	Advanced Colorectal Adenocarcinoma \| Pancreatic Cancer First line \| Second line	222	BMS-813160 300 mg two times a day+gem/nabP+nivolumab	oinaokmsuh(qtckyiyhoc) = Two dose-limiting toxicities (rash and pericardial effusion with pericarditis, both grade 3) occurred ibnvcftrds (ufgbotedrz ) View more	Positive	01 Jan 2026
				BMS-813160 300 mg two times a day+gem/nabP
ESMO_IO2023	Phase 2	Hepatocellular Carcinoma \| Non-Small Cell Lung Cancer	36	Nivolumab + BMS-813160 (CCR2/5i)	soeantlsif(zrzupvxvmg) = euuviupnwm ystullaeaz (ysznjksmyq )	-	07 Dec 2023
NCT03767582 (ASCO_GI2023) Manual	Phase 1	Pancreatic Ductal Adenocarcinoma	13	Nivolumab 480mg+BMS-813160 150mg/300mg+GVAX 5x108 cells	zephthqwhr(gkqzkgakpg) = xfhkyuwfvv uwavyoylnq (gcnrdvsuoz ) View more	Positive	24 Jan 2023
NCT03496662 (CTgov)	Phase 1/2	Pancreatic Ductal Adenocarcinoma	40	Peripheral blood+Nivolumab+Nab-paclitaxel+Gemcitabine+BMS-813160 (Part A - Experimental Dose Level 0)	zzptlvialc = xadsvkxfgh fyzhnqjeol (satmelrfgy, rycoisoznx - paxntfnjai) View more	-	30 Nov 2022
				Peripheral blood+Nab-paclitaxel+Gemcitabine (Part A - Control (Chemotherapy Only))	hnensrvpxe(mjdvhxneto) = xpzrjzjwfz ehkmbletcs (qgmtaucjlg, bcskbdqbjk - lrbrydmqjr) View more
NCT01752985 (CTgov)	Phase 2	Diabetes Mellitus, Type 2 \| Diabetic Nephropathies	319	BMS-813160 (BMS-813160 150 mg QD)	dtvfcyxtme(guntbvdetb) = owodpbcscg jqubegmlqk (vaeixzxykw, 48.994) View more	-	25 Jun 2019
				BMS-813160 (BMS-813160 300 mg BID)	dtvfcyxtme(guntbvdetb) = eyiuuxbrfe jqubegmlqk (vaeixzxykw, 62.795) View more