Exherin (ADH-1) / Fennec Pharma - LARVOL DELTA

A phase I study of ADH-1 with cisplatin (Cisp) and gemcitabine (Gem) in patients (Pts) with unresectable or metastatic pancreatic and biliary tract cancers. (ASCO-GI 2017) - P1; "The phase II dose of ADH1 given with Cisp/Gem is 2,000 mg IV twice weekly. ADH-1 was relatively well tolerated. Most pts ultimately required dose delays or reductions due to cumulative toxicity with Cisp/Gem."

P1 data • Biliary Cancer • Biosimilar • Gastrointestinal Cancer • Immunology • Oncology • Pancreatic Cancer

Safety, Tolerability, Pharmacodynamics and Pharmacokinetics, and Efficacy of CLTX-305 in Autosomal Dominant Hypocalcemia Type 1 (ADH1) (clinicaltrials.gov) - P2b; N=20; Not yet recruiting; Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)

Clinical • New P2b trial • Endocrine Disorders • Hypoparathyroidism • Renal Disease

Zinc starvation induces autophagy in yeast. (PubMed) - J Biol Chem - "...Abundant zinc proteins, such as Adh1, Fba1, and ribosomal protein Rpl37, were degraded in an autophagy-dependent manner. But the targets of autophagy were not restricted to zinc-binding proteins. When cellular zinc is severely depleted, this non-selective autophagy plays a role in releasing zinc from the degraded proteins and recycling zinc for other essential purposes."

Journal • Biosimilar

Mucosal Antibodies to the C-terminus of Toxin A Prevent Colonization of Clostridium difficile. (PubMed) - Infect Immun - "As well as neutralizing toxins, antibodies to TcdA26-39 (but not to toxoids), whether raised to the recombinant protein, or to TcdA26-39 expressed on the B. subtilis spore surface, cross-react with a number of seemingly unrelated proteins expressed on the vegetative cell surface or spore coat of C. difficile This includes, two dehydrogenases, AdhE1 and LdhA, as well as the CdeC protein that is present on the spore. Anti-TcdA26-39 mucosal antibodies obtained following immunization with recombinant B. subtilis spores were able to reduce adhesion of C. difficile to mucus-producing intestinal cells. This cross-reaction is intriguing yet important since it illustrates the importance of mucosal immunity for complete protection to CDI."

Journal • Biosimilar • Immunology

Long term clinical follow-up of atypical ductal hyperplasia and lobular carcinoma in situ in breast core needle biopsies. (PubMed) - Pathology - "Significantly more women with LCIS developed invasive carcinoma or DCIS than women with ADH on long term follow-up. The relative risk for ADH and LCIS on core biopsy with a negative excision compared with FCC was similar to that reported in the literature (ADH 1-7×, LCIS 3-19×)."

Journal • Biosimilar • Oncology

Tumor endothelial cell-derived cadherin-2 promotes angiogenesis and has prognostic significance for lung adenocarcinoma. (PubMed, Mol Cancer) - "...Loss- or gain-of-function analysis showed that CDH2 significantly promoted in vitro and in vivo angiogenesis and sensitivity to the antagonist exherin...Moreover, high CDH2 expression in TECs was significantly associated with tumor stage, visceral pleural metastasis, and decreased overall survival in patients with ADC but not SCC. Together, these data indicate the importance of CDH2 in angiogenesis and highlight its potential both for antiangiogenic therapy and as a candidate prognostic marker for ADC."

Journal