CXCR1

IRVINE, CA / ACCESSWIRE / November 15, 2023 / GeneTex, a multinational antibody manufacturer, announces a new addition to its growing product line of validated recombinant monoclonal antibodies against G protein-coupled receptors (GPCRs). CXC motif chemokine receptor 2 (CXCR2) belongs to the family of 20 human chemokine receptors responsible for signal transduction triggered by the binding of one or more of 46 chemokines. Chemokines and their respective receptors, which normally are involved in the immune response, are also active in a plethora of diseases, including inflammatory and autoimmune disorders, neurological disease, and solid and hematologic cancers, among others. Though there is a significant body of literature on chemokines, there are fewer studies on the receptors. Novel reagents that are specific for particular CXC (and other chemokine) receptors are essential to promote additional research. CXCR2 Antibody [HL2604] Validation CXCR2 Antibody [HL2604] testing on GPCR array, IHC analysis, and Western blot analysis. Human GPCRs are expressed by over 820 genes that code for highly dynamic, seven-transmembrane domain proteins that respond to ligands of various types. GPCRs elicit profound physiological and pathophysiological effects that are relevant to many chronic diseases, including type 2 diabetes mellitus, malignancies, mood disorders, obesity, and neurodegenerative disease. Approximately 350 of the non-olfactory GPCRs are considered amenable to pharmaceutical intervention, though the vast majority remain without available drugs. Research into GPCR biology is of great importance, and GeneTex is committed to producing a comprehensive GPCR antibody portfolio to promote this work. Due to well-known technical challenges associated with antibody development for specific GPCR targets, GeneTex employs enhanced and/or novel validation modalities to establish specificity among GPCR family members, particularly those that share sequence identity. These strategies include knockout/knockdown testing, immunohistochemistry (IHC) or immunocytochemistry (ICC/IF) staining of tissues/cells with differential target expression, and comparison of signals between antibodies against the same target, among other approaches. In addition, GeneTex is incorporating the innovative VirDTM-GPCR arrays (CDI Labs, Baltimore, MD) to determine specificity. In the case of the new recombinant monoclonal CXCR2 antibody (GTX639056), this array demonstrates absolute specificity for CXCR2, with no cross-reactivity detected for CXCR1, CXCR3, CXCR4, CXCR5, and CXCR6. This is particularly significant as CXCR1 and CXCR2 share the highest similarity with ~77% sequence identity. This array data is complemented by both western blot (WB) and IHC validation. As expected, the WB shows a significantly more robust signal in a "membrane extract" fraction compared to the matching "whole cell extract" sample. For IHC, human pancreatic cancer tissue staining reveals the anticipated signal enrichment in the cytoplasm and at the cell membrane. GeneTex is committed to providing the most extensive and thoroughly validated recombinant monoclonal antibody repertoire for GPCR proteins. For the chemokine receptors specifically, efforts are currently underway to broaden the catalog of reagents against the remaining CXC, CC, CX3C, and XC receptors. This same large-scale approach will be applied to all six families of proteins within the GPCR superfamily. Contact Information Allen Lee Vice President - Business Development allensl@genetex.com (949)553-1900 SOURCE: GeneTex, Inc. View source version on accesswire.com:

-- Phase 1 Findings Presented in Oral Session at 2022 American Society of Hematology (ASH) Meeting Support CXCR1/2 as Promising Target in MDS – -- 50 Percent of Patients Treated with the Recommended Phase 2 Dose Achieved an Objective Response (mCR, Hematologic Improvement) -- AUBURN, Wash., Dec. 9, 2022 /PRNewswire/ -- Syntrix Pharmaceuticals today announced results from a single-arm, open-label Phase 1 trial of single-agent SX-682, an investigational CXCR1/2 inhibitor, in patients with any-risk myelodysplastic syndromes (MDS) in whom front-line hypomethylating-agent (HMA) had failed, a high unmet need population. Results support the clinical activity of SX-682. The data will be presented by David Sallman, MD of the H. Lee Moffitt Cancer Center and Research Institute, an investigator for the clinical trial, during an afternoon oral session on December 12, 2022 at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract #855). At this planned interim analysis after dose-escalation, 17 patients had been treated with twice-daily (BID) oral doses of 25 (n=3), 50 (n=3), 100 (n=3), 200 (n=6) and 400 (n=2) mg SX-682 in six continuous 28-day cycles with responding patients continuing treatment. All patients were transfusion-dependent and all had failed prior HMA and 24% lenalidomide (range 1-4 failed prior therapies). The median age was 76, and patients were low (n=1), intermediate-1 (n=10), intermediate-2 (n=5) and high (n=1) risk by the International Prognostic Scoring System (IPSS). There was a dose-dependent increase in overall response rate (ORR) from 0% at 25 mg BID to 50% at 200 mg BID (response assessments per 2006 IWG MDS criteria). Across all doses, 8 of 17 (47%) patients had a reduction in marrow blasts after initiating SX-682 with 2 of 6 pts (33%) achieving a marrow complete remission (mCR) at the 200 mg BID dose. There was hematologic improvement (HI) in 3 patients with one having a durable near-CR response (on SX-682 >500 days) consisting of trilineage HI (hemoglobin > 10 g/dL) and transfusion independence for over 4 months (patient required 16 transfusions in the 7 weeks before starting SX-682 therapy). SX-682 was well tolerated with no maximally tolerated dose and no patient discontinued treatment for adverse events. Treatment-emergent adverse events > grade 3 were most common in the 200 and 400 mg dose cohorts, and those related to neutrophils were consistent with being related to SX-682. Effects on neutrophils reversed on cessation of drug dosing. Based on pharmacodynamic response, ORR, marrow blast responses and safety, the 200 mg BID dose was selected for the expansion phase of the trial. "Results presented at ASH reinforce the clinical potential of CXCR1/2 inhibition with SX-682 in patients with MDS failing frontline HMA therapy," said John Zebala, MD, PhD, President and CEO, Syntrix Pharmaceuticals. "We look forward to initiating additional trials in MDS and AML, which will be a significant step forward for this exciting next-generation therapy targeting both leukemic cell growth and the disease-promoting bone marrow immune microenvironment." SX-682 is investigational and not approved anywhere globally. Its efficacy and safety have not been established. More information about clinical trials with SX-682 is available at . About Myelodysplastic Syndromes (MDS) Myelodysplastic syndromes (MDS) are a type of cancer caused by poorly formed or dysfunctional blood cells in the bone marrow. Approximately 15,000 people are diagnosed with MDS in the U.S. each year, and no treatments with new mechanisms have been approved in 14 years. MDS can also develop into AML. Approximately 20,000 Americans will be diagnosed with AML each year. About the Phase 1 Trial This Phase 1 dose-escalation with expansion study, which is being funded by the National Heart and Lung and Blood Institute (NHLBI) of the NIH (HL142389, NCT04245397), is designed to evaluate the safety, tolerability and efficacy of single-agent SX-682 in HMA failure MDS. Patients are treated with BID doses of SX-682 in six continuous 28-day cycles with responding patients continuing treatment. Response assessment is at the end of cycles 1, 3 and 6 and every third cycle thereafter using IWG criteria. This trial, which is ongoing, aims to enroll a total of 40 patients in the expansion phase of the trial. About SX-682 SX-682 is an oral allosteric small-molecule inhibitor of CXCR1 and CXCR2 (CXCR1/2) being investigated in several Phase 1/2 clinical trials. CXCR1/2 is a signaling pathway that acts as a "master switch" in the tumor microenvironment. It is involved in the recruitment of immunosuppressive MDSCs and autocrine growth of disease-initiating leukemic stem cells in AML and myelodysplastic syndromes (MDS). CXCR2 overexpression is predictive of transfusion dependence in MDS. CXCR2 inhibition reduces proliferation of leukemic cell lines and primary MDS/AML patient samples in vitro. SX-682 has been validated in major solid tumor models, where it exhibits mono-agent activity, blocks metastasis, depletes MDSCs, activates infiltration and killing by immune effector cells, reverses chemo-resistance, and enhances immune-checkpoint blockade. About Syntrix Syntrix is a pharmaceutical company committed to discovering and delivering innovative therapies to solve the most difficult clinical problems. Convergent Science & Strategy. Breakthrough Medicines. Disclosure Notice This release contains forward-looking information that is based on company management's current beliefs and expectations and are subject to currently unknown information, risks and circumstances. Actual results may vary from what is projected. Syntrix does not undertake any obligation to publicly update these forward-looking statements, whether as a result of new information, future events or otherwise. Media Contact: Aaron Schuler, PhD, 253-833-8009, x21 SOURCE Syntrix Pharmaceuticals