DSTA4637S / Roche, Servier, Pfizer - LARVOL DELTA

Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates. (PubMed, Front Chem) - "The multi-targeted TD-1792, for instance, retained potent antibacterial activities against multiple strains that are resistant to its constituent, vancomycin...DSTA4637S is a pioneer antibacterial agent under clinical development and represents a novel class of bacterial therapy, that is, antibody-antibiotic conjugates. DSTA4637S is effective against the notorious persistent S. aureus bacteremia, a revelation of the abracadabra potential of antibiotic hybrid approaches."

Clinical • Journal • Review • Infectious Disease

[VIRTUAL] A Phase 1b, Randomized, Double-blind, Placebo-controlled, Multiple-ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Patients with staphylococcus Aureus Bacteremia Receiving Standard-of-care Antibiotics (IDWeek 2020) - "DSTA4637S in patients with complicated SAB demonstrated increased IRRs and decreased exposure compared to healthy volunteers, highlighting the importance of Phase I studies of novel treatments in infected SAB patients and not simply healthy controls."

Clinical • P1 data • PK/PD data • Infectious Disease

[VIRTUAL] Comparison of Pharmacokinetics of DSTA4637S, a novel THIOMABTM Antibody-Antibiotic Conjugate, in Patients with Staphylococcus aureus Bacteremia Receiving Standard-of-Care Antibiotics with Pharmacokinetics in Healthy Volunteers (IDWeek 2020) - "DSTA4637S PK analysis demonstrated lower exposures in patients with S. aureus bacteremia compared to HVs. Potential explanations for reduced exposures include factors related to disease status, non-specific organ uptake, and target-mediated clearance."

Clinical • PK/PD data • Infectious Disease

"Discontinuations: RG7861 (anti S aureus ADC?) partnered with $SGEN. RG6000 = dual leucine zipper kinase inhibitor for ALS. $RHHBY" (@JacobPlieth)

A phase 1, randomized, single ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti-Staphylococcus aureus THIOMAB™ antibody-antibiotic conjugate, in healthy volunteers. (PubMed, Antimicrob Agents Chemother) - P1 | "No DSTA4637S-induced anti-drug antibody responses were observed. DSTA4637S was generally safe and well tolerated as a single i.v. dose in healthy volunteers. DSTA4637S has a favorable safety and pharmacokinetic profile that supports future development as a novel therapeutic for S. aureus infections."

Clinical • Journal • P1 data • PK/PD data

Preclinical and translational pharmacokinetics of a novel THIOMAB™ antibody-antibiotic conjugate against Staphylococcus aureus. (PubMed, MAbs) - "DSTA4637S, a novel THIOMAB™ antibody-antibiotic conjugate (TAC) against Staphylococcus aureus (S...This work provides insights into PK behaviors of DSTA4637A in preclinical species and informs clinical translatability of these observed results and further clinical development. Abbreviations: ADC: Antibody-drug conjugate; AUC: time curve extrapolated to infinity; ac-dmDNA31: antibody-conjugated dmDNA31; C: maximum concentration observed; DAR: drug-to-antibody ratio; CL: clearance; CL: distribution clearance; CL: systemic clearance of all DAR species; k: deconjugation rate constant; PK: Pharmacokinetics; IV: Intravenous; IgG: Immunoglobulin G; mAb: monoclonal antibody; S. aureus: Staphylococcus aureus; TAC: THIOMAB antibody-antibiotic conjugate; TDC: THIOMAB antibody-drug conjugate; TAb: total antibody; t: terminal half-life; vc linker: valine-citrulline linker; V: volume of distribution at steady state; V: volume of distribution for the central compartment; V: the volume..."

Journal • PK/PD data • Preclinical

Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Participants With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care (SOC) Antibiotics (clinicaltrials.gov) - P1; N=27; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion

Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Participants With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care (SOC) Antibiotics (clinicaltrials.gov) - P1; N=27; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Participants With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care (SOC) Antibiotics (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Feb 2019 ➔ Nov 2019; Trial primary completion date: Feb 2019 ➔ Nov 2019

Clinical • Trial completion date • Trial primary completion date