Delving into the Latest Updates on Ulocuplumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

CXCR4

Mechanism

CXCR4 antagonists(C-X-C motif chemokine receptor 4 antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Pancreatic CancerSmall Cell Lung Cancer

Inactive Indication

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaB-Cell Malignant Neoplasm+ [10]

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol Myers Squibb Co.

Inactive Organization

Medarex, Inc.

University of Bari

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Gene Sequence

Sequence Code 9976464H

Source: *****

Sequence Code 12985782L

Source: *****

Extensive research on the CXCL12-CXCR4 axis in acute myeloid leukemia (AML) has resulted in the incorporation of novel anti-leukemia drugs targeting this axis into therapeutic strategies. However, despite this progress, a comprehensive and up-to-date review addressing the role of the CXCL12-CXCR4 axis in AML's oncogenic processes is lacking. In this review, we examine its molecular aspects influencing cancer progression, such as its impact on autonomous proliferation, apoptotic regulation, chemoresistance mechanisms, and interactions with non-leukemic cells such as MSCs and T_reg cells. Additionally, we explore clinical implications, including prognosis, correlation with WBC count, blast count in the bone marrow and peripheral blood, as well as its association with FLT3-ITD, NPM1 mutations, and FAB classification. Finally, this paper extensively discusses drugs that specifically target the CXCL12-CXCR4 axis, including plerixafor/AMD3100, ulocuplumab, peptide E5, and motixafortide, shedding light on their potential therapeutic value in the treatment of AML.

01 Sep 2024·Expert Opinion on Investigational Drugs

Investigational CXCR4 inhibitors in early phase development for the treatment of hematological malignancies

Review

Author: Zimbo, Annamaria ; Martino, Enrica Antonia ; Labanca, Caterina ; Mendicino, Francesco ; Lucia, Eugenio ; Vigna, Ernesto ; Olivito, Virginia ; Neri, Antonino ; Bruzzese, Antonella ; Stanzione, Gaia ; Pozzi, Stefano ; Gentile, Massimo ; Morabito, Fortunato

INTRODUCTIONCXCR4/CXCL12 axis regulates cell proliferation, survival, and differentiation, as well as the homing and mobilization of hematopoietic stem cells (HSCs) from bone marrow niches to the peripheral blood. Furthermore, CXCR4 and CXCL12 are key mediators of cross-talk between hematological malignancies and their microenvironments. CXCR4 overexpression drives disease progression, boosts tumor cell survival, and promotes chemoresistance, leading to poor prognosis.AREAS COVEREDIn light of these discoveries, scientific investigations, and clinical trials have underscored the therapeutic promise found in small-molecule antagonists like plerixafor, peptides/peptidomimetics, such as BKT140, monoclonal antibodies like PF-06747143 and ulocuplumab, as well as microRNAs. Their efficacy is evident in reducing tumor burden, inducing apoptosis and sensitizing malignant cells to conventional chemotherapies. This overview delves into the pathogenic role of the CXC4/CXCL12 axis in hematological neoplasms and examines the clinical application of key CXCR4 antagonists.EXPERT OPINIONThe information collectively emphasizes the potential of CXCR4 antagonists as a therapeutic strategy for hematologic malignancies, showcasing advancements in preclinical and clinical studies. As these therapeutic strategies progress through clinical trials, their potential to reshape the prognosis of hematologic malignancies will become increasingly apparent.

01 Aug 2022·Clinical Lymphoma Myeloma and Leukemia

SOHO State of the Art Updates and Next Questions: Targeted therapies and emerging novel treatment approaches for Waldenström Macroglobulinemia

Review

Author: Castillo, Jorge J ; Sarosiek, Shayna ; Branagan, Andrew R ; Treon, Steven P ; Sermer, David

Waldenström Macroglobulinemia (WM) is a rare hematologic malignancy characterized by the presence of lymphoplasmacytic lymphoma cells involving the bone marrow and production of a monoclonal IgM paraprotein. Recurrent somatic mutations in MYD88^L265P and CXCR4 have been reported in 90% to 95% and 30% to 40% of patients with WM, respectively. Standard treatment regimens combine the anti-CD20 antibody rituximab with alkylating agents (eg, bendamustine, cyclophosphamide), nucleoside analogs (eg, fludarabine, cladribine), or proteasome inhibitors (eg, bortezomib, carfilzomib, and ixazomib). Covalent BTK inhibitors (eg, ibrutinib, acalabrutinib, zanubrutinib) have shown to be safe and highly effective in patients with WM. Novel and promising agents in this disease include next-generation covalent BTK inhibitors (eg, tirabrutinib, orelabrutinib), non-covalent BTK inhibitors (eg, pirtobrutinib, ARQ531), BCL-2 antagonists (eg, venetoclax), and CXCR4-targeted agents (eg, mavorixafor, ulocuplumab), among others. Future studies will focus on developing fixed-duration combinations regimens with these novel agents aimed at increasing durable responses while minimizing toxicity and cost.

1

News (Medical) associated with Ulocuplumab

07 Jun 2023

·www.biospace.com

AbTherx Launches a Next-Generation Antibody Discovery Platform

The company brings together a proven team and novel technologies to increase efficiencies in antibody discovery MOUNTAIN VIEW and SAN DIEGO, CA / ACCESSWIRE / June 7, 2023 / AbTherx, Inc., a privately held biotech company with novel technologies that accelerate antibody discovery, announced the launch of its next-generation human antibody discovery platform. AbTherx's novel transgenic mouse technologies, Atlas™ Mice, include a clinically validated bispecific antibody format most similar to a native antibody configuration and a long CDR3 antibody technology using native human sequences that improves results against challenging targets such as GPCRs and ion channels. AbTherx is also increasing access to transgenic mice expressing full human antibody diversity. Through technology licensing and research collaborations, AbTherx partners with drug developers of all sizes to overcome the most demanding challenges for advancing innovative medicines. The AbTherx leadership team has over 100 years of combined experience in antibody discovery and transgenic mouse technologies, including the development of the HuMAb Mouse® technology at Medarex and Bristol Myers Squib (BMS). The HuMAb Mouse technology is the world's most successful human antibody discovery platform, responsible for 13 marketed therapeutics. Justin Mika, CEO, has served in executive and advisory roles in successful biotechnology, drug discovery platform, and healthcare investment organizations for over 15 years. His most recent position was CEO of AlivaMab Discovery Services, where he led the organization through a period of rapid growth. Peter Brams, PhD, CSO, has spent his career focused on the discovery of clinical-grade human antibodies, e.g., Opdivo®, Arzerra®, and Kesimpta®, and notable GPCR-targeting clinical candidates, e.g., Ulocuplumab (anti-CXCR4) and anti-CCR8 antibodies. Peter grew the antibody-discovery unit at Medarex to meet the needs of the worldwide BMS organization. Dan Rohrer, PhD, CTO, has over 25 years of broad experience in antibody discovery. Over the last 20 years, Dan has specialized in creating human antibody discovery platforms, including developing the HuMAb Mouse platform - the preeminent platform based on FDA approvals. Additionally, Dan has an established background and publication record in GPCR biology and transgenic modeling. In addition to Mr. Mika, Dr. Brams, and Dr. Rohrer, AbTherx has attracted industry veterans Brian Conn as CFO, Catherine Kara as Head of IP, David Passmore as Head of Business Development, and Stacey Borders as Marketing and Communications Strategist. "It is exciting to launch this company and begin actualizing the positive impact we will have on the future of medicine," said Justin Mika, Chief Executive Officer of AbTherx. "Transgenic mouse technologies remain the most proven option for discovering and developing antibody therapeutics; however, there was room for improvement. Atlas Mice were thoughtfully designed to address legacy technology limitations and barriers." "Our prior experience developing, managing, and implementing transgenic technologies has allowed us to build a proprietary and scalable core technology with novel features that are particularly focused on enabling the needs of the modern drug generation market," said Dan Rohrer, Chief Technology Officer of AbTherx. "Atlas Mice can be rapidly adapted to meet the most pressing challenges in therapeutic antibody discovery and development; these tools are focused around native antibody structures, and the design principles are integrated with immunization and screening know-how to maximize discovery potential." About AbTherx, Inc. AbTherx, Inc. was founded in 2023 and is advancing medicine with novel technologies that accelerate and enable therapeutic antibody discovery. The company was founded by a leadership team with over 100 years of combined experience in antibody discovery and platform development, including development of the HuMAb Mouse® technology, the most successful human antibody discovery platform with 13 marketed therapeutics. AbTherx's Atlas™ Mouse platform enables the development of a clinically validated bispecific antibody format most similar to native antibodies and uses natural mechanisms to generate long CDR3 antibodies to improve the chance of success against challenging drug targets such as GPCRs and ion channels. AbTherx is also increasing access to transgenic mice expressing full human antibody diversity. Through technology licensing and research collaborations, AbTherx partners with drug developers of all sizes to overcome the most demanding challenges in delivering innovative medicines. For more information, please visit . Media Contact Stacey Borders stacey@abtherx.com SOURCE: AbTherx, Inc. View source version on accesswire.com:

Executive Change

100 Deals associated with Ulocuplumab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Ulocuplumab	-	DB12018

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Cancer	Phase 2	-	Bristol Myers Squibb Co.	-
Small Cell Lung Cancer	Phase 2	-	Bristol Myers Squibb Co.	-
Metastatic Solid Tumor	Preclinical	US	Bristol Myers Squibb Co.	13 Jul 2015
Solid tumor	Preclinical	FI	Bristol Myers Squibb Co.	13 Jul 2015
Solid tumor	Preclinical	US	Bristol Myers Squibb Co.	13 Jul 2015
Leukemia	Preclinical	CA	Bristol Myers Squibb Co.	27 Jan 2015
Leukemia	Preclinical	IT	Bristol Myers Squibb Co.	27 Jan 2015
Leukemia	Preclinical	IL	Bristol Myers Squibb Co.	27 Jan 2015
Leukemia	Preclinical	BR	Bristol Myers Squibb Co.	27 Jan 2015
Acute Myeloid Leukemia	Discovery	US	Bristol Myers Squibb Co.	25 Dec 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03225716 (CTgov)	Phase 1	Waldenstrom Macroglobulinemia	13	Ulocuplumab+Ibrutinib (Phase 1 Dose Level 1: Ibrutinib + Ulocuplumab 400mg Cycle 1 and 800mg Cycles 2-6)	kgbjmerqxs(qjcwwgfcmg) = hmmiwayvdm lvdyfzheid (xapttdpqsb, zpnhxdeems - sjrjqbxrqz) View more	-	03 May 2024
				Ulocuplumab+Ibrutinib (Phase 1 Dose Level 3: Ibrutinib + Ulocuplumab 800mg Cycle 1 and 1600mg Cycles 2-6)	kgbjmerqxs(qjcwwgfcmg) = gyklxpyiqz lvdyfzheid (xapttdpqsb, isgqngmzky - shfxzoekro) View more
NCT03225716 (Pubmed \| Circulation) Manual	Phase 1	Waldenstrom Macroglobulinemia CXCR4 Mutation	13	Ibrutinib+ulocuplumab	(uihlntyzrf) = udmvjeyvie vijskjglfo (vhrfzssxnp ) View more	Positive	28 Oct 2021
NCT02305563 (CTgov)	Phase 1/2	Acute Myeloid Leukemia	70	LDAC - Ph1+ULO (ULO 600mg + LDAC - Ph1)	tpmlvqhyad(itazqyjgyn) = erjpeqtdzf mhjuxykuhd (sxcwuyugvu, kdciwpijns - izqharsnow) View more	-	16 Sep 2021
				LDAC - Ph1+ULO (ULO 800mg + LDAC - Ph1)	tpmlvqhyad(itazqyjgyn) = ujobtssapd mhjuxykuhd (sxcwuyugvu, wgfwsscmiq - anvdoofqht) View more
NCT01359657 (Pubmed \| Clin Cancer Res) Manual	Phase 1/2	Multiple Myeloma	46	Ulocuplumab+Lenalidomide+Dexamethasone	(nyowfpabsg) = boeaemzamc hfooiwmmbz (cftbqdizoa ) View more	Positive	15 Jan 2020
				Ulocuplumab+Bortezomib+Dexamethasone	-
NCT02472977 (CXCessoR4, CTgov)	Phase 1/2	Metastatic Solid Tumor	61	ulocuplumab+nivolumab (PAC DL1 (DLT))	(gqaguqlnoq) = axygqgrsdt rrvlinutbx (jtmklnelgx, iyzbevqosg - mriqkpcopn) View more	-	29 Mar 2018
				ulocuplumab+nivolumab (PAC DL-1 (Tot))	(gqaguqlnoq) = fmlsctbpkb rrvlinutbx (jtmklnelgx, etopikgabv - uxdzxkduuf) View more