A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections

The purpose of this study is to demonstrate the efficacy and evaluate the safety, and tolerability of mavorixafor in participants with congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorders who are experiencing recurrent and/or serious infections as assessed by demonstrating its clinical benefit and increasing levels of circulating neutrophils.

Start Date01 Mar 2024

Sponsor / Collaborator

X4 Pharmaceuticals, Inc.

NCT05103917 / Unknown statusPhase 1/2

An Open Label, Phase Ib/II Trial to Study the Safety, Tolerability and Antitumor Activity of X4P-001 in Combination With Toripalimab in Patients With Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)

Objectives Phase 1b
Primary Objectives:
To evaluate the safety and tolerability of X4P-001 combined with toriplimab in patients with locally advanced or metastatic TNBC
Secondary Objectives:
To characterize the pharmacokinetics (PK) profile of X4P-001 alone or combined with toriplimab
To characterize the antitumor activity of X4P-001 in combination with toriplimab in patients with locally advanced or metastatic TNBC(according to RECIST 1.1)
To characterize the overall survival of X4P-001 in combination with toriplimab in patients with locally advanced or metastatic TNBC
To characterize the immunogenicity of toriplimab when administrated in combination with X4P-001

Start Date21 Jul 2021

Sponsor / Collaborator

Abbisko Therapeutics Co., Ltd.

NCT04154488 / Active, not recruitingPhase 1/2

A Phase 1b/2, Open-Label, Multicenter Study of Mavorixafor in Patients With Congenital Neutropenia and Chronic Neutropenia Disorders

This is a 2-part study of mavorixafor in participants diagnosed with chronic neutropenia. The main goal of Part 1 (Phase 1b) is to help researchers learn more about how the investigational medicine, mavorixafor, impacts people living with chronic neutropenia (including congenital, idiopathic, and cyclic). In Part 2 (Phase 2), the safety and tolerability of chronic dosing of mavorixafor will be evaluated in a larger participant population and the impact of 6-month chronic dosing of mavorixafor on participant neutropenia.

Start Date16 Oct 2020

Sponsor / Collaborator

X4 Pharmaceuticals, Inc.

100 Clinical Results associated with Mavorixafor

100 Translational Medicine associated with Mavorixafor

100 Patents (Medical) associated with Mavorixafor

Literatures (Medical) associated with Mavorixafor

22 Dec 2023·Bioscience reports

Biological and mutational analyses of CXCR4–antagonist interactions and design of new antagonistic analogs

Article

Author: Wu, Yi ; Ciechanover, Aaron ; Huang, Lina S M ; Xu, Yan ; Zhu, Ruohan ; Mao, Yujia ; Huang, Ziwei ; An, Jing ; Meng, Qian ; Zhu, Siyu

Abstract:

The chemokine receptor CXCR4 has become an attractive therapeutic target for HIV-1 infection, hematopoietic stem cell mobilization, and cancer metastasis. A wide variety of synthetic antagonists of CXCR4 have been developed and studied for a growing list of clinical applications. To compare the biological effects of different antagonists on CXCR4 functions and their common and/or distinctive molecular interactions with the receptor, we conducted head-to-head comparative cell-based biological and mutational analyses of the interactions with CXCR4 of eleven reported antagonists, including HC4319, DV3, DV1, DV1 dimer, V1, vMIP-II, CVX15, LY2510924, IT1t, AMD3100, and AMD11070 that were representative of different structural classes of D-peptides, L-peptide, natural chemokine, cyclic peptides, and small molecules. The results were rationalized by molecular modeling of CXCR4–antagonist interactions from which the common as well as different receptor binding sites of these antagonists were derived, revealing a number of important residues such as W94, D97, H113, D171, D262, and E288, mostly of negative charge. To further examine this finding, we designed and synthesized new antagonistic analogs by adding positively charged residues Arg to a D-peptide template to enhance the postulated charge–charge interactions. The newly designed analogs displayed significantly increased binding to CXCR4, which supports the notion that negatively charged residues of CXCR4 can engage in interactions with moieties of positive charge of the antagonistic ligands. The results from these mutational, modeling and new analog design studies shed new insight into the molecular mechanisms of different types of antagonists in recognizing CXCR4 and guide the development of new therapeutic agents.

02 Dec 2023·Expert review of hematology

The promise of novel treatments for severe chronic neutropenia

Review

Author: Dale, David C ; Bolyard, Audrey Anna ; Makaryan, Vahagn

INTRODUCTION:

Severe chronic neutropenia, i.e. absolute neutrophil count (ANC) less than 0.5 × 10⁹/L, is a serious health problem because it predisposes patients to recurrent bacterial infections. Management radically changed with the discovery that granulocyte colony-stimulating factor (G-CSF) could be used to effectively treat most patients; therapy required regular subcutaneous injections. In the early days of G-CSF therapy, there were concerns that it might somehow overstimulate the bone marrow and cause myelodysplasia (MDS) or acute myeloid leukemia (AML). Detailed research records from the Severe Chronic Neutropenia International Registry (SCNIR) indicate that this is a relatively low-risk event. The research records suggest that certain patient groups are primarily at risk. Presently, allogeneic hematopoietic stem cell therapy serves as an alternate form of therapy.

AREAS COVERED:

Due to these concerns and the desire for an easy-to-take oral alternative, several new treatments are under investigation. These treatments include neutrophil elastase inhibitors, SGLT-2 inhibitors, mavorixafor - an oral CXCR4 inhibitor, gene therapy, and gene editing.

EXPERT OPINION:

All of these alternatives to G-CSF are promising. The risks, relative benefits, and costs are yet to be determined.

01 Jul 2023·Combinatorial chemistry & high throughput screening

Bioinformatics Analysis to Identify Intersection Genes, Associated Pathways and Therapeutic Drugs between COVID-19 and Oral Candidiasis

Article

Author: Yang, Liuqing ; Tao, Lu ; Gao, Ying ; Huang, Handan ; Yang, Nan ; Sui, Xin ; Yu, Jinling ; Liu, Zhihui

Background::

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a serious threat to human health. Oral candidiasis (OC) may be one of the causes of morbidity in severe COVID-19 patients. However, there is currently no treatment for oral candidiasis and COVID-19 (OC/COVID-19). The purpose of this study was to use text mining and data analysis to investigate the target genes for treatment and explore potential therapeutic drugs for OC/COVID-19.

Methods::

We used the text mining tool pubmed2ensembl to detect genes associated with OC, and the dataset GSE164805 was used for the data analysis. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on two intersection genes using the Database of Annotation, Visualization and Integrated Discovery (DAVID) platform. The protein-protein interaction (PPI) networks were constructed by STRING software, and gene module analysis was performed using Molecular Complex Detection (MCODE), a plug-in in Cytoscape. The most significant genes were selected as hub genes and their functions and pathways were analyzed using Metascape. We revealed the upstream pathway activity of the hub genes. The drug-gene interaction database (DGIdb) and the traditional Chinese medicines integrated database (TCMID) were used to discover potential drugs for the treatment of OC/COVID-19.

Results::

The analysis indicated that there were 2869 differentially expressed genes (DEGs) in GSE164805. We identified 161 unique genes associated with oral candidiasis through text mining. A total of 20 intersection genes were identified as the therapeutic targets for OC/COVID-19. Based on the bioinformatics analysis, nine genes (TNF, IL1B, IFNG, CSF2, ELANE, CCL2, MMP9, CXCR4, and IL1A) were identified as hub genes that were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications and NOD-like receptor signaling pathway. We identified four of the nine genes that target five existing drugs, including BKT140, mavorixafor, sivelestat, canakinumab, and rilonacept. Furthermore, twenty herb ingredients were also screened as potential drugs.

Conclusion::

In this study, TNF, IL1B, IFNG, CSF2, ELANE, CCL2, MMP9, CXCR4, and IL1A were potentially key genes involved in the treatment of OC/COVID-19. Taken together five drugs and twenty herb ingredients were identified as potential therapeutic agents for OC/COVID-19 treatment and management.

News (Medical) associated with Mavorixafor

03 Jun 2024

·www.globenewswire.com

X4 Pharmaceuticals Announces Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

BOSTON, June 03, 2024 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced that, effective on May 31, 2024, the company issued inducement awards to new employees under the X4 Pharmaceuticals, Inc. 2019 Inducement Equity Incentive Plan (the “2019 Inducement Plan”). The 2019 Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously an employee of X4. The inducement awards consist of options to purchase an aggregate of 166,353 shares of X4’s common stock. These stock awards were granted as an inducement material to the new employees entering into employment with X4 in accordance with Nasdaq Listing Rule 5635(c)(4) and were approved by X4’s Compensation Committee of the Board of Directors. The options have a ten-year term and an exercise price of $1.01 per share, which is equal to the closing price of X4’s common stock on May 31, 2024. Each option will vest over a four-year period, with 25% of the shares vesting after 12 months and the remaining shares vesting monthly over the following 36 months, subject to the employee’s continued employment with X4 on such vesting dates. The options are subject to the terms and conditions of the 2019 Inducement Plan and the terms and conditions of an award agreement covering the grant. About X4 Pharmaceuticals X4 is delivering progress for patients by developing and commercializing innovative therapies for those with rare diseases of the immune system and significant unmet needs. Leveraging our expertise in CXCR4 and immune system biology, we have successfully developed mavorixafor, which has received U.S. approval as XOLREMDI™ (mavorixafor) capsules in its first indication. We are also evaluating the use of mavorixafor in additional potential indications. X4 corporate headquarters are in Boston, Massachusetts and our research center of excellence is in Vienna, Austria. For more information, please visit our website at www.x4pharma.com. Company Contact:José Juves Head of Corporate & Patient Affairsjose.juves@x4pharma.com Investor Contact:Daniel FerryManaging Director, LifeSci Advisorsdaniel@lifesciadvisors.com (617) 430-7576

29 May 2024

·www.globenewswire.com

X4 Pharmaceuticals to Host Virtual Investor Event on June 27, 2024 to Review New Mavorixafor Clinical Data from Ongoing Phase 2 Trial in Chronic Neutropenia

Webcast to include interim hematological results from at least 15 trial participants and feature experts in the treatment of chronic neutropeniaBOSTON, May 29, 2024 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced that it will host a virtual investor event on Thursday, June 27, 2024 at 8:00 am ET. To register for the event, click here. The event will focus on new interim results from an ongoing Phase 2 clinical trial exploring the use of mavorixafor as a once-daily oral treatment in patients with chronic neutropenia (CN). The data to be presented will include hematological results from at least 15 study participants treated with either mavorixafor monotherapy or mavorixafor in combination with stable doses of injectable granulocyte colony-stimulating factor (G-CSF). Physician expert commentary on the clinical results and the high unmet need in CN will also be included as part of the event. As previously communicated, the company plans to initiate a global, pivotal Phase 3 clinical trial in the current quarter that aims to evaluate the efficacy, safety, and tolerability of oral once-daily mavorixafor (with or without G-CSF) in people with congenital or acquired primary autoimmune and idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections. A live question and answer session will follow the formal presentation. About Chronic Neutropenia and MavorixaforChronic neutropenic disorders are rare blood conditions lasting more than three months, persistently or intermittently, and characterized by increased risk of infections and reduced quality of life due to persistent, abnormally low levels of neutrophils circulating in the blood. Neutrophils are retained in the bone marrow by the CXCR4/CXCL12 axis, creating a reserve of cells; downregulation of the CXCR4 receptor by G-CSF or inhibition of the receptor by mavorixafor, an orally active CXCR4 antagonist, has been shown to mobilize neutrophils from the bone marrow into the peripheral blood. About X4 PharmaceuticalsX4 is delivering progress for patients by developing and commercializing innovative therapies for those with rare diseases of the immune system and significant unmet needs. Leveraging our expertise in CXCR4 and immune system biology, we have successfully developed mavorixafor, which has received U.S. approval as XOLREMDI™ (mavorixafor) capsules in its first indication. We are also evaluating the use of mavorixafor in additional potential indications. X4 corporate headquarters are in Boston, Massachusetts and our research center of excellence is in Vienna, Austria. For more information, please visit our website at www.x4pharma.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by the words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target,” or other similar terms or expressions that concern X4's expectations, strategy, plans, or intentions. Forward-looking statements include, without limitation, implied or express statements regarding the clinical progress of X4’s pipeline development programs including its interim clinical results from its ongoing Phase 2 clinical trial; uncertainties inherent in the initiation and completion of clinical trials and clinical development; the risk that trials and studies may not have satisfactory outcomes; the risk that the outcomes of preclinical studies or earlier clinical trials will not be predictive of later clinical trial results; the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials; and the potential adverse effects arising from the testing or use of mavorixafor or other product candidates. Any forward-looking statements in this press release are based on management's current expectations and beliefs. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond X4’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements, including the risks that: X4 may not be able to obtain regulatory approval for, or successfully commercialize, mavorixafor or any other product candidate for other chronic neutropenic disorders or any other potential indication; the expected availability, content, and timing of clinical data from X4’s ongoing clinical trials of mavorixafor may be delayed or unavailable; the clinical trial design and rate of enrollment for clinical trials as well as potential therapeutic benefits, including the current design for of a potential Phase 3 clinical trial evaluating mavorixafor in certain chronic neutropenic disorders and its expected initiation in the first half of 2024 may not enable successful completion of the trial(s); uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development; trials and studies may not have satisfactory outcomes; the outcomes of preclinical studies or earlier clinical trials will not be predictive of later clinical trial results; initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials; and the potential adverse safety effects arising from the testing or use of mavorixafor or other product candidates and other risks and uncertainties, including those described in the section entitled “Risk Factors” in X4’s Annual Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 7, 2024, and in other filings X4 makes with the SEC from time to time. X4 undertakes no obligation to update the information contained in this press release to reflect new events or circumstances, except as required by law. Company Contact:José Juves Head of Corporate & Patient Affairsjose.juves@x4pharma.com Investor Contact:Daniel Ferry Managing Director, LifeSci Advisorsdaniel@lifesciadvisors.com (617) 430-7576

Phase 2

13 May 2024

·www.globenewswire.com

X4 Pharmaceuticals to Participate in the H.C. Wainwright 2nd Annual BioConnect Investor Conference

BOSTON, May 13, 2024 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced that management will be participating in the upcoming H.C. Wainwright 2nd Annual BioConnect Investor Conference, taking place on May 20th, 2024, at the Nasdaq Stock Exchange in New York City. H.C. Wainwright 2nd Annual BioConnect Investor ConferenceDate: Monday, May 20, 2024Time: 2:00 PM ETFormat: Fireside ChatWebcast Link About X4 PharmaceuticalsX4 is delivering progress for patients by developing and commercializing innovative therapies for those with rare diseases of the immune system and significant unmet needs. Leveraging our expertise in CXCR4 and immune system biology, we have successfully developed mavorixafor, which has received U.S. approval as XOLREMDI™ (mavorixafor) capsules in its first indication. We are also evaluating the use of mavorixafor in additional potential indications. X4 corporate headquarters are in Boston, Massachusetts and our research center of excellence is in Vienna, Austria. For more information, please visit our website at www.x4pharma.com. Company Contact:José JuvesHead of Corporate & Patient Affairsjose.juves@x4pharma.com Investor Contact:Daniel FerryManaging Director, LifeSci Advisorsdaniel@lifesciadvisors.com(617) 430-7576

Drug Approval

100 Deals associated with Mavorixafor

External Link

KEGG	Wiki	ATC	Drug Bank
D11510	-	-	DB05501

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
WHIM Syndrome	US	X4 Pharmaceuticals, Inc.	26 Apr 2024

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neutropenia	Phase 3	-	X4 Pharmaceuticals, Inc.	01 Mar 2024
Triple Negative Breast Cancer	Phase 2	CN	Abbisko Therapeutics Co., Ltd.	07 Apr 2021
Triple Negative Breast Cancer	Phase 2	CN	Mayne Pharma, Inc.	07 Apr 2021
Triple Negative Breast Cancer	Phase 2	CN	X4 Pharmaceuticals, Inc.	07 Apr 2021
Neutropenia, Nonimmune Chronic Idiopathic, Adult	Phase 2	US	X4 Pharmaceuticals, Inc.	16 Oct 2020
Neutropenia, Severe Chronic	Phase 2	US	X4 Pharmaceuticals, Inc.	16 Oct 2020
Neutropenia, Severe Congenital, Autosomal Recessive 3	Phase 2	US	X4 Pharmaceuticals, Inc.	16 Oct 2020
Advanced Renal Cell Carcinoma	Phase 2	US	X4 Pharmaceuticals, Inc.	01 Jan 2016
Advanced Renal Cell Carcinoma	Phase 2	KR	X4 Pharmaceuticals, Inc.	01 Jan 2016
Waldenstrom Macroglobulinemia	Phase 1	US	X4 Pharmaceuticals, Inc.	30 Apr 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03995108 (FDA_CDER) Manual	Phase 3	WHIM Syndrome	31	XOLREMDI	okbawlogob(ousnalydfu) = xoqioeppxc dtqylrmwxe (uywcqxfwji, 1.89) View more	Positive	26 Apr 2024
NCT03995108 (EHA2023)	Phase 3	WHIM Syndrome	31	Mavorixafor	cjcfxbesvi(jkfquousjh) = increased from baseline into normal range and sustained at each timepoint assessed over 52 weeks with mavorixafor versus placebo fdxxompttt (tyttulixbx ) View more	Positive	08 Jun 2023
NCT03995108 (EHA2023)	Phase 3	WHIM Syndrome	31	Placebo		Positive	08 Jun 2023
NCT02923531 (CTgov)	Phase 1/2	Renal Cell Carcinoma	9	nivolumab+X4P-001	qsasfsdtzb(bffiutjmdv) = gdisbnyhrc ftbkwcczlm (ndgkesecuw, awpgenxpgh - isnebgdbtt) View more	-	29 Dec 2022
NCT03995108 (4WHIM, EHA2022) Manual	Phase 3	WHIM Syndrome	31	MAVORIXAFOR	xpxobqojxr(eyfuxbnhec) = dklxkmflvz vjkjkutacg (nmtpblejsj ) View more	Positive	10 Jun 2022
NCT03995108 (4WHIM, EHA2022) Manual	Phase 3	WHIM Syndrome	31	Placebo	xpxobqojxr(eyfuxbnhec) = vqtuswfgho vjkjkutacg (nmtpblejsj ) View more	Positive	10 Jun 2022
NCT04274738 (ASH2021) Manual	Phase 1	Waldenstrom Macroglobulinemia MYD88 Mutation \| CXCR4 Mutation	10	Mavorixafor+ibrutinib	zfqbaffiix(hxuxecvsye) = 1 event (grade 3 hypertension) oyjucqlsgp (ncjpztdycc )	Positive	05 Nov 2021
NCT03005327 (ASH2021) Manual	Phase 2	WHIM Syndrome	8	mavorixafor (long-term extension)	nngjvaelth(vmvdtiiwzc) = 12 grade 1 events sltksunxvc (iekqfjkcpn ) View more	Positive	05 Nov 2021
NCT02923531 (Pubmed \| Invest New Drugs) Manual	Phase 1	Advanced Renal Cell Carcinoma	9	nivolumab+Mavorixafor	dfxoxvcxoo(ycqrkebzem) = qrpwbrrinr edxmycmqlp (rmraxmxniz ) View more	Positive	01 Aug 2021
NCT04274738 (EHA2021) Manual	Phase 1	Lymphoplasmacytic Lymphoma CXCR4 Mutation \| MYD88 Mutation	7	ibrutinib+Mavorixafor	vgprlszula(hnirjqbgcg) = usedxkduuq xdozjqyegx (kygcjalfrv ) View more	Positive	09 Jun 2021
NCT03005327 (Pubmed \| Circulation) Manual	Phase 2	WHIM Syndrome	8	mavorixafor	bbzlaeirer(aqmihebffp) = nuuumxqgke vzaclglfcg (tqwvkyeies ) View more	Positive	24 Dec 2020
X4P-001-RCCA (ESMO2019)	Phase 1/2	Advanced Renal Cell Carcinoma	65	X4P-001 + Axitinib	agqwdwqwmh(cbuplybcnl) = 29 Pts, 45% pibdkjywdo (xyycrwftvr ) View more	-	30 Sep 2019

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