edratide (hCDR1) / XTL Biopharma - LARVOL DELTA

Characterization of anti-CD3 antibodies in clinically available bispecific T cell engagers. (PubMed, Semin Hematol) - "Specifically, antibodies were assigned to the same family if their six CDRs-HCDR1-3 and LCDR1-3-exhibited ≥80% pairwise sequence identity upon multiple sequence alignment...Interestingly, mosunetuzumab (Family 4) showed remarkably lower incidence of adverse events such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infection compared to other bispecific TCEs even though its affinity for CD3ε was not significantly different. The epitopes of 4 antibodies in Family 2, teclistamab, talquetamab, glofitamab, and tarlatamab were previously defined to be located at the N-terminal region of CD3ε via hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis...Blinatumomab (Family 1) and tebentafusp (Family 6) did not bind to the CD3ε homolog of the cynomolgus monkey, whereas the other 8 bispecific TCEs did. This lack of cross-reactivity poses clear disadvantages in their preclinical development, particularly for..."

Journal • Infectious Disease • Inflammation • Oncology

Developing drug-like single-domain antibodies (VHH) from in vitro libraries. (PubMed, MAbs) - "The HCDR1 and HCDR2 sequences were derived from human VH3 family next-generation sequencing datasets informatically purged of sequence liabilities, synthesized as array-based oligonucleotides, cloned as single CDR libraries into each of the parental scaffolds and filtered for protein A binding by yeast display to ensure correct folding and display...A broad diversity of high affinity (100 pM-10 nM), developable binders was directly isolated, with developability evaluated for most assays using the isolated VHHs, rather than fused to Fc, which is customary. This represents the first systematic developability assessment of isolated VHH molecules."

Journal • Preclinical • CDR2

XTL Biopharmaceuticals Ltd. Enters into Definitive Exclusive Sublicense Agreement with Biossil Inc. [Google translation] (Zonebourse) - "On March 4, 2025, XTL Biopharmaceuticals Ltd. announced that it had entered into a definitive exclusive sublicense agreement (the 'Agreement') with Biossil Inc...Under the Agreement, the Company will grant to Biossil, for the term of the Agreement, an exclusive, royalty-free, worldwide, perpetual sublicense, with the right to sublicense through multiple tiers, to its novel synthetic peptide, hCDR1, including the patent applications and provisional applications and resulting patents listed in the Agreement, as well as all know-how, including all clinical and preclinical data relating to the product called Edratide (the 'Product'), trademarks, trade names, logos and labeling owned or controlled by the Company or its affiliates that are necessary or useful for the research, development, manufacturing and/or commercialization of the Product...the Company will be entitled to cumulative payments in an amount not exceeding approximately USD 11,500,000."

Licensing / partnership • Lupus

Adaptive immune receptor germline gene variation. (PubMed, Curr Opin Immunol) - "Experimental and genetic evidence has demonstrated that the complementarity determining regions 1 and 2 (HCDR1 and HCDR2), encoded by the variable (V) region of TCRs and BCRs, also often make critical contacts with the targeted antigen. Thus, knowledge about allelic variation in the genes encoding TCRs and BCRs is critically important for understanding adaptive immune responses in outbred populations and to define responder and non-responder phenotypes."

IO biomarker • Journal • Review • Immunology • Infectious Disease

A key F27I substitution within HCDR1 facilitates the rapid maturation of P2C-1F11-like neutralizing antibodies in a SARS-CoV-2-infected donor. (PubMed, Cell Rep) - "Using deep sequencing, we explore the dynamics of antibody repertoire in a SARS-CoV-2-infected donor, from whom the potent and broad nAb P2C-1F11 (the parent version of Brii-196) was previously isolated. Using sequence alignment, structure modeling, and bioactivity analysis based on site-mutated assay, we demonstrate that a key substitution F27I in heavy chain contributes significantly to the maturation of P2C-1F11-like antibodies. Overall, our findings elucidate the developmental process and maturation pathway of P2C-1F11, providing some important information for the design of novel immunogens to elicit more potent nAbs against SARS-CoV-2 infection."

Journal • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies. (PubMed, Clin Rev Allergy Immunol) - "Recently, synthetic mimic peptides (hCDR1, pCONs, DWEYS, FISLE-412, and ALW) that directly block anti-dsDNA autoantibodies have attracted attention, which could ameliorate lupus, decrease the serological autoantibody titer, reduce the deposition of renal autoantibodies, and improve pathological performance. These potent small peptide molecules are well tolerated, non-toxic, and non-immunogenic, which have demonstrated a benign safety profile and are expected to be hopeful candidates for SLE management. In this review, we clarify the role of anti-dsDNA antibodies in SLE, mainly focus on the current strategies targeting anti-dsDNA antibodies, and discuss their potential clinical value."

Journal • Review • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • BTK

Is this a bubble or reality: XTL Biopharmaceuticals Ltd (XTLB) stock sky-rocketed in the pre-market session? (Stocks Telegraph) - "The XTLbio pipeline mainly emphasizes systematically identifying, validating, and in-licensing therapeutic candidates...Today 3 compounds are actively being developed, all in clinical stages. hCDR1 is currently undergoing Phase 3 testing at XTL Biopharmaceuticals, and is on the top of their drug development program....acting through an entirely novel mechanism of action, for the management of Systemic Lupus Erythematosus has been generated."

Trial status • Immunology • Lupus • Systemic Lupus Erythematosus

DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously. (PubMed, Nat Commun) - "We report the development of a platform of dual targeting Fab (DutaFab) molecules, which comprise two spatially separated and independent binding sites within the human antibody CDR loops: the so-called H-side paratope encompassing HCDR1, HCDR3 and LCDR2, and the L-side paratope encompassing LCDR1, LCDR3 and HCDR2...In the present study, this platform is applied to generate DutaFabs specific for VEGFA and PDGF-BB, which show high affinities, physico-chemical stability and solubility, as well as superior efficacy over anti-VEGF monotherapy in vivo. These molecules exemplify the usefulness of DutaFabs as a distinct class of antibody therapeutics, which is currently being evaluated in patients."

Journal

XTL Biopharmaceuticals reports financial and operational results for the full year ended 2013 (PRNewswire) - Anticipated new P2 trial for lupus in Q4 2014 or Q1 2015

Anticipated new P2 trial • Lupus

XTL Biopharmaceuticals announces new patent filing in U.S.for lupus drug hCDR1 (XTL Biopharmaceuticals Press Release) - "XTL Biopharmaceuticals...today announced that it has filed a new patent application with the U.S. Patent and Trademark Office to protect doses of hCDR1 lower than 0.5 mg weekly, in the treatment of Systemic Lupus Erythematosus (SLE)."

Patent • Lupus

Indoleamine-2,3-dioxygenase in murine and human systemic lupus erythematosus: Down-regulation by the tolerogeneic peptide hCDR1. (PubMed, Clin Immunol) - "Diminished IDO gene expression was associated with hCDR1 beneficial effects. Our results suggest that the hCDR1-induced FOXP3 expressing regulatory T cells in lupus are not driven by IDO but rather by other hCDR1 regulated pathways."

Journal • Preclinical

The tolerogenic peptide hCDR1 immunomodulates cytokine and regulatory molecule gene expression in blood mononuclear cells of primary Sjogren's syndrome patients. (PubMed, Clin Immunol) - "IDO inhibition led to a significant decrease in the expression of FOXP3 which is crucial for the induction of T regulatory cells. Thus, hCDR1 is potential candidate for the specific treatment of pSS patients."

Clinical • IO Biomarker • Journal