Nanofitin / Affilogic - LARVOL DELTA

A Multispecific Checkpoint Inhibitor Nanofitin with a Fast Tumor Accumulation Property and Anti-Tumor Activity in Immune Competent Mice. (PubMed, Biomolecules) - "This activity was further correlated with Nanofitin's tumor accumulation at 7 h post-injection, which was highest for the B10-B11-ABNF. This study highlights the potential of bispecific Nanofitins, particularly with albumin binding to enable rapid and uniform tumor accumulation of effective PD-L1 immunotherapy."

Checkpoint inhibition • Journal • Preclinical • Oncology • EGFR

Complete preclinical evaluation of the novel antibody mimetic Nanofitin-IRDye800CW for diverse non-invasive diagnostic applications in the management of HER-2 positive tumors. (PubMed, Sci Rep) - "There are well-known limitations associated to the use of antibodies in the non-invasive detection of HER-2 expression. In the latter, NF-800 was compared to the anti-HER-2 antibody Trastuzumab, displaying a large diagnostic advantage. Interestingly, NF-800 did not seem to share the same binding site with Trastuzumab and Pertuzumab, opening specific theragnostic opportunities for NF-800 in combination with standard-of-care antibodies."

Journal • Preclinical • Oncology • HER-2

Enhancing Oral Delivery of Biologics: A Non-Competitive and Cross-Reactive Anti-Leptin Receptor Nanofitin Demonstrates a Gut-Crossing Capacity in an Ex Vivo Porcine Intestinal Model. (PubMed, Pharmaceutics) - "This particular Nanofitin was selected for its absence of competition with leptin, its cross-reactivity with LepR from human, mouse, and pig hosts, and its shuttle capability associated with its ability to induce a receptor-mediated transport. This study paves the way for future in vivo demonstration of a safe and efficient oral-to-systemic delivery of targeted therapies."

Journal • Preclinical • Gastrointestinal Disorder • LEP • LEPR

Targeted Nanofitin-drug conjugates achieve efficient tumor delivery and therapeutic effect in an EGFR-positive mouse xenograft model. (PubMed, Mol Cancer Ther) - "Internalization was found critical for efficient release of the toxin. Hence, the intravenous administration of the D8-based construct showed significant anti-tumor effect in vivo as determined by monitoring tumor volumes and bioluminescence levels over 2 months."

Journal • Preclinical • Oncology • EGFR

Inhalable Nanofitin demonstrates high neutralization of SARS-CoV-2 virus via direct application in respiratory tract. (PubMed, Mol Ther) - "In addition, we reported the stability and the conserved activity of the tetrameric construction after nebulization. This advantageous developability feature for pulmonary administration associated with the ease of assembly, as well as the fast generation process position the Nanofitin technology as a potential therapeutic solution for emerging infectious diseases."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Engineering of a Bispecific Nanofitin with Immune Checkpoint Inhibitory Activity Conditioned by the Cross-Arm Binding to EGFR and PDL1. (PubMed, Biomolecules) - "We demonstrated that affinity-attenuated bispecific Nanofitin could elicit PDL1 blockade exclusively in an EGFR-directed manner. Overall, the data collected highlight the potential of this approach to enhance the selectivity and safety of PDL1 checkpoint inhibition."

Checkpoint inhibition • Journal • Immune Modulation • Oncology • EGFR • PD-L1

Development of versatile affinity-based system for one step purification process: case of Group A Streptococcus vaccine. (PubMed, Biotechnol Bioeng) - "The system consists of the association of custom ligands based on the Nanofitin protein scaffold, with Eshmuno® industry-grade chromatography medium...The single-step affinity purification consistently delivered high purity product (above >90%) and improved performances compared to the current three-step process: reduced process time and footprint (3 to 1 step) and increased product yields (0.31 g vs 0.04g of SLO per kg of harvest broth). The custom affinity system herein described can potentially be applied to any biologic for which a specific Nanofitin is identified, thus establishing a platform with a strong impact on the manufacturing of vaccines and other biological targets."

Journal • Infectious Disease

Discovery of APL-1030, a Novel, High-Affinity Nanofitin Inhibitor of C3-Mediated Complement Activation. (PubMed, Biomolecules) - "APL-1030 is a novel, high-affinity inhibitor of primate C3-mediated complement activation developed from natural amino acids on the hyperthermophilic Nanofitin platform. Its properties may support novel drug candidates, enabling bifunctional moieties, gene therapy, and tissue-targeted C3 pharmacologics for diseases with high unmet need."

Journal • Gene Therapies

Albumin Binding Nanofitins, a new scaffold to extend half-life of Biologics - a case study with exenatide peptide. (PubMed, Peptides) - "A new strategy of peptide half-life extension has been evaluated. This study constitutes a proof-of-concept of in vivo half-life extension of a biologic using an ABNF. Besides, the absence of cysteine in the Nanofitin scaffold, which is therefore devoid of structuring disulfide bonds, allows manufacturing in microbial cost effective systems."

Journal

Gastrobodies are engineered antibody mimetics resilient to pepsin and hydrochloric acid. (PubMed, Commun Biol) - "Two stable scaffold proteins (nanobody and nanofitin), previously developed to be protease-resistant, were completely digested in less than 10 min at 100-fold lower concentration of pepsin than found in the stomach...Anti-GTD binders retained high stability to acid, digestive proteases and heat. Gastrobodies show resilience to exceptionally harsh conditions, which should provide a foundation for targeting and modulating function within the GI tract."

Journal • Gastrointestinal Disorder

Nanofitins targeting heat shock protein 110: an innovative immunotherapeutic modality in cancer. (PubMed, Int J Cancer) - "In this work, as an alternative to neutralizing antibodies, Nanofitins (scaffold ~7 kDa-proteins) targeting HSP110 were isolated from the screening of a synthetic Nanofitin library, and their capacity to bind (immunoprecipitation, biolayer interferometry) and to inhibit HSP110 was analyzed in vitro and in vivo...Finally, we showed the complementarity between A-C2 and an anti-PD-L1 strategy in the in vivo and in ovo tumor models. Altogether, Nanofitins appear to be promising new immunotherapeutic lead compounds."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HSPH1