valziflocept (OHB-101) / Takeda, Oak Hill Bio - LARVOL DELTA

Serine affects engulfment during the sporulation process in Clostridium perfringens strain SM101. (PubMed, Anaerobe) - "These results suggest that Ser accelerated the early stage of sporulation of C. perfringens strain SM101, but disturbed the engulfment process, resulting in reduction of sporulation. To the best of our knowledge, this is the first study reporting that an amino acid affects engulfment during the C. perfringens sporulation process."

Journal

Inhibitory effects of sucrose palmitic acid ester on the germination-to-outgrowth process of Clostridium perfringens SM101 spores. (PubMed, Int J Food Microbiol) - "In contrast, the presence of SEPA completely blocked the "outgrowth stage," in which the newly synthesized vegetative cell body emerges from the cracked spore shell. The results demonstrate that SEPA inhibits the revival process of the spores of a pathogenic strain of C. perfringens and that the site of its action is the "outgrowth stage" and not the "germination stage," as evidenced by single- cell analysis."

Journal

Overexpressing the cpr1953 Orphan Histidine Kinase Gene in the Absence of cpr1954 Orphan Histidine Kinase Gene Expression, or Vice Versa, Is Sufficient to Obtain Significant Sporulation and Strong Production of Clostridium perfringens Enterotoxin or Spo0A by Clostridium perfringens Type F Strain SM101. (PubMed, Toxins (Basel)) - "These findings suggest that CPR1953 and CPR1954 do not function together in a step-wise manner, e.g., as a novel phosphorelay. Instead, it appears that, at natural expression levels, the independent kinase activities of both CPR1953 and CPR1954 are necessary for obtaining sufficient Spo0A production and phosphorylation to initiate sporulation and CPE production."

Journal

Identification of Germinants and Expression of Germination Genes in Clostridium perfringens Strains Isolated from Diarrheic Animals. (PubMed, Pathogens) - "Our study found the following (i) animal strains spores germinated at a slower rate with AK (mixture of L-asparagine and KCl), L-cysteine, or L-lysine, but the extent of germination varied based on strains and germinants used; (ii) none of the amino acids (excluding L-cysteine and L-lysine) were identified as a universal germinant for spores of animal strains; (iii) animal strain spores germinated better at a pH range of 6.0-7.0; (iv) all tested germination-specific genes were expressed in animal strains; the levels of expression of major germinant receptor gene (gerKC) were higher and the cortex hydrolysis machinery genes (cspB and sleC) were lower in animal strains, compared to the food poisoning strain SM101; and (v) the levels of CspB and SleC were significantly lower in spores of animal strains compared to strain SM101, suggesting that these animal strains lack an efficient spore cortex hydrolysis machinery. In summary, our findings suggest that the poor or slow..."

Journal

Identification of orphan histidine kinases that impact sporulation and enterotoxin production by Clostridium perfringens type F strain SM101 in a pathophysiologically-relevant ex vivo mouse intestinal contents model. (PubMed, PLoS Pathog) - "In addition, the CPR1954 mutant exhibited little or no Spo0A phosphorylation in MDS cultures. These studies, i) highlight the importance of using pathophysiologically-relevant models to investigate C. perfringens sporulation and CPE production in a disease context and ii) link the CPR1953 and CPR1954 kinases to C. perfringens sporulation and CPE production in disease-relevant conditions."

Journal • Preclinical

Characterization of NanR Regulation of Sialidase Production, Sporulation and Enterotoxin Production by Clostridium perfringens Type F Strains Carrying a Chromosomal Enterotoxin Gene. (PubMed, Toxins (Basel)) - "In vegetative medium, the nanR null mutants of both strains produced more spores than their parents while NanR repressed sialidase activity in SM101 but positively regulated sialidase activity in 01E809. These results demonstrate that NanR regulates important virulence functions of c-cpe strains, with this control varying depending on strain and culture conditions."

Journal • CPE

Identification of the common differentially expressed genes and pathogenesis between neuropathic pain and aging. (PubMed, Front Neurosci) - "Aldesleukin, Valziflocept, MGD-010, Cinryze, and Rhucin were the potential effective drugs in neuropathic pain and aging. This study identified co-DEGs, revealed molecular mechanisms, demonstrated the immune microenvironment, and predicted the possible TFs, miRNAs regulation networks and new drug targets for neuropathic pain and aging, providing novel insights into further research."

Journal • Neuralgia • Pain • CD4 • CD8 • MIR363 • NCAM1

Characterization of Putative Sporulation and Germination Genes in Clostridium perfringens Food-Poisoning Strain SM101. (PubMed, Microorganisms) - "The germination, outgrowth, and colony formation defects of ΔytxC or ΔyyaC2 spores were restored when ΔytxC or ΔyyaC2 mutant was complemented with wild-type ytxC or yyaC2, respectively. Collectively, our current study identified new sporulation and germination genes in C. perfringens."

Journal

Reasons to be cheerful: One, two, three? (BSR 2017) - "Three different monoclonal antibodies (Rontalizumab, Silfalimumab and Anifrolumab) have been used in major clinical trials in SLE. For example, the importance of an increased interferon-alpha signature in the development of SLE is widely recognised. However other ongoing phase II trials utilising a novel recombinant FcɣIIB receptor [SM101] and RNP peptide (Lupuzor previously known as PI140) are now underway after encouraging animal-model and/or phase I studies. Benlysta which blocks the B-cell activating factor BAFF remains the only biologic to be formally approved in the UK and the USA for the treatment of lupus albeit under significant restrictions. Frustratingly, other approaches, for example, the use of Abatacept which blocks the antigen-presenting cell-T-cell interaction have not met their endpoints in clinical trials. In retrospect the significantly heterogeneous nature of lupus was always likely to make it more challenging to respond to individual biologic approaches. ...

Biosimilar • Immunology • Lupus • Psoriasis • Rheumatoid Arthritis

Baxter buys SuppreMol in €200m deal (Pharmaceutical Business Review (PBR)) - "The bioscience division of Baxter International Inc. has acquired German privately held biopharmaceutical company SuppreMol GmbH for €200m...Baxter will also own SuppreMol's complete early-stage development portfolio of novel biologic immunoregulatory therapeutics for the treatment of autoimmune diseases..."

M&A • Immunology • Lupus

RelA/DTD-mediated regulation of spore formation and toxin production by Clostridium perfringens type A strain SM101. (PubMed, Microbiology) - "Collectively, our results demonstrate that RelA modulates cellular physiology such as growth, spore formation and toxin production by C. perfringens type A strain SM101, although DTD also plays a role in these pleiotropic functions in coordination with RelA during sporulation. These findings have implications for the understanding of the mechanisms involved in the infectious cycle of C. perfringens."

Journal • Biosimilar

Analysis of the spore membrane proteome in Clostridium perfringens implicates cyanophycin in spore assembly. (PubMed) - J Bacteriol - "A cyanophycin synthetase mutant was constructed and found to make spores with altered morphology but normal heat resistance, suggesting cyanophycin plays a different role inC. perfringensthan it does in cyanobacteria."

Journal • Biosimilar

Baxter: Investor Conference (Baxter) - “Positive POC For SM101 In Systemic Lupus Erythematosus (SLE)”; “Overall Response At 24 Weeks (All Patients)”; “SLE responder index is composite endpoint based on: Overall Responder included SLEDAI, BILAG and PGA scores, The SLE responder index was primary endpoint in the Belimumab (Benlysta) pivotal studies”

P2a data • Lupus

Next-generation Fc receptor-targeting biologics for autoimmune diseases. (PubMed, Autoimmun Rev) - "These include PF-06755347 (GL-2045), CSL730 (M230), CSL777 and Pan Fc Receptor Interacting Molecule (PRIM). Neonatal Fc receptor (FcRn)-targeting therapeutics block the FcRn receptor and are represented by candidate drugs such as the Fc fragment efgartigimod and the monoclonal antibodies rozanolixizumab (UCB7665), M281 and SYNT001. Finally, Fc and FcγR-targeting therapeutics, comprise molecules that target the Fc of IgG, such as the recombinant soluble FcγIIb receptor valziflocept (SM101/SHP652) and various monoclonal antibodies directed against the receptors...Although initial results are promising, further long-term data and a better understanding of the unique mechanisms of action of the different molecules are needed. The efficacy, safety, convenience of administration, duration of effects, and cost will all contribute to determining which of the molecules will be successful in the clinic."

Journal • Review