Vyrologix (leronlimab)

P2, N=60, Not yet recruiting, CytoDyn, Inc.

Apart from that, the MD simulation study also disclosed stable binding interactions of DH-18 and MMP-2 along with crucial interactions with active site amino acid residues namely His120, Glu121, His124, His130, Pro140, and Tyr142. In a nutshell, this study highlighted the importance of biphenylsulfonamide-based novel and promising MMP-2 inhibitors to open up a new avenue for potential therapy against CML.

Inhibitors of CCR5 (CCR5i), either small molecules (maraviroc, vicriviroc) or humanized monoclonal antibodies (leronlimab) have shown anti-tumor and anti-metastatic properties in preclinical studies. In early clinical studies, reviewed herein, CCR5i have shown promising results and evidence for effects on both the tumor and the anti-tumor immune response. Current clinical studies have therefore included combination therapy approaches with checkpoint inhibitors.

P2, N=0, Withdrawn, CytoDyn, Inc.

P1/2, N=48, Active, not recruiting, CytoDyn, Inc. | Trial completion date: Jun 2022 --> Sep 2022 | Trial primary completion date: Mar 2022 --> Jul 2022

P2, N=12, Terminated, CytoDyn, Inc. | N=60 --> 12 | Trial completion date: Dec 2019 --> Sep 2021 | Recruiting --> Terminated | Trial primary completion date: Dec 2019 --> Apr 2021; Lack of enrolment

P1/2, N=48, Active, not recruiting, CytoDyn, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2022 --> Jun 2022 | Trial primary completion date: Nov 2021 --> Mar 2022

P1/2, N=48, Recruiting, CytoDyn, Inc. | Trial primary completion date: Mar 2020 --> Nov 2021

Leronlimab (PRO 140), a CCR5 antagonist mAb, in combination with carboplatin is currently enrolling newly diagnosed mTNBC. The preliminary analysis shows safety and tolerability of the combination and continue to enroll patients with initial promising clinical activity, potentially suggesting the future availability of a new effective agent in the management of this serious condition.

P, Available, CytoDyn, Inc.

This study will provide an overview of approved chemokine receptor antagonists and promising candidates in advanced clinical trials.Areas covered: We will describe clinical aspects of chemokine receptor antagonists regarding their clinical efficacy, mechanisms of action, and re-purposed applications.Expert opinion: Three chemokine antagonists have been approved: (i) plerixafor is a small-molecule CXCR4 antagonist that mobilizes hematopoietic stem cells; (ii) maraviroc is a small-molecule CCR5 antagonist for anti-HIV treatment; and (iii) mogamulizumab is a monoclonal-antibody CCR4 antagonist for the treatment of mycosis fungoides or Sézary syndrome. Moreover, phase 3 trials are ongoing to evaluate many potent candidates, including CCR5 antagonists (e.g. leronlimab), dual CCR2/CCR5 antagonists (e.g. cenicriviroc), and CXCR4 antagonists (e.g. balixafortide, mavorixafor, motixafortide). The success of chemokine receptor antagonists depends on the selective blockage of disease-relevant chemokine receptors which are indispensable for disease progression. Although clinical translation has been slow, antagonists targeting chemokine receptors with multifaced functions offer the potential to treat a broad spectrum of human diseases.

A CCR5 targeted cancer clinical trials (phase 1) using a small molecule inhibitor with the check point inhibitor Pembrolizumab opened to accrual in late 2018 NCT03274804...Based on these studies a phase 1b/2 clinical trial was approved for Leronlimab and carboplatin treatment of metastatic TNBC (NCT03838367) and granted fast track designation in May 2019...Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular metastasis with a clinical trial currently accruing. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy.