- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Preclinical, Journal: In vitro Antimicrobial Activity and Dose Optimization of Eravacycline and Other Tetracycline Derivatives Against Levofloxacin-Non-Susceptible and/or Trimethoprim-Sulfamethoxazole-Resistant Stenotrophomonas maltophilia. (Pubmed Central) - Sep 14, 2023
In contrast, the CFR of tigecycline was less than 40%, even at a dose of 100 mg q12 h. For pneumonia, minocycline is better for S. maltophilia that is non-susceptible to LVFX; for TMP-SMZ-resistant strains and strains that are not susceptible to either LVFX or TMP-SMZ, the efficiency of eravacycline requires further evaluation. Eravacycline may be a better choice for extremely resistant S. maltophilia strains that are non-susceptible to LVFX, TMP-SMZ, and minocycline.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, samotolisib (LY3023414) / Eli Lilly
Trial completion, Trial completion date, Metastases: ExIST: LY3023414 and Prexasertib in Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - Sep 11, 2023
P2, N=10, Completed,
Eravacycline may be a better choice for extremely resistant S. maltophilia strains that are non-susceptible to LVFX, TMP-SMZ, and minocycline. Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Nov 2022
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
An Unusual Case of Clostridium Peritonitis From Small Intestinal Source (Exhibit Hall) - Jul 29, 2023 - Abstract #ACG2023ACG_1618;
Previously reported cases of Clostridium in the small bowel postulate that ileal hypomotility and histologic changes in small intestine epithelium with alteration in fecal flow as seen in the setting of ileorectal anastomosis may predispose patients to this bacteria. Unfortunately, there is no clear antibiotic regimen for these patients and overall with small bowel Clostridium involvement this renders a poor prognosis as seen with our patient.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Or eravacycline (Twitter) - Jul 29, 2023
- |||||||||| cefepime/zidebactam IV (WCK 5222) / Wockhardt, Fetroja (cefiderocol) / Shionogi, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Preclinical, Journal: Determination of potential combination of non-?-lactam, ?-lactam, and ?-lactamase inhibitors/?-lactam enhancer against class D oxacillinases producing Acinetobacter baumannii: Evidence from in-vitro, molecular docking and dynamics simulation. (Pubmed Central) - Jul 21, 2023
The binding energies obtained from MM-PBSA shed light on the binding efficiencies of each non-BL, BL, and BLI/BLE, thereby helping us to propose the drug combinations. Based on the MD trajectories scoring acquired, we propose using eravacycline, cefepime/zidebactam, cefiderocol/zidebactam, and eravacycline in combination with durlobactam or zidebactam would be promising for treating OXA-23, OXA-24, and OXA-58 like expressing A. baumannii infections.
- |||||||||| Zerbaxa (ceftolozane /tazobactam) / Merck (MSD), Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva, Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
Retrospective data, Review, Journal: Comparing novel antibiotics and carbapenems for complicated intra-abdominal infections: A systematic review and meta-analysis of randomized controlled trials. (Pubmed Central) - Jul 18, 2023
Clinical efficacy, microbiological response and safety of the novel antibiotics, including ceftazidime-avibactam, ceftolozane-tazobactam and eravacycline, are comparable to carbapenems for the treatment of patients with cIAIs. These agents can be potential therapeutic options as carbapenem-sparing antibiotics for cIAIs.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Trial completion date, Trial initiation date, Trial primary completion date: Prospective Evaluation of Xerava Prophylaxis in Hematological Malignancy Patients With Prolonged Neutropenia (clinicaltrials.gov) - Jun 26, 2023
P2, N=55, Not yet recruiting,
This brings the translation between mouse and human brain PK one step further. Trial completion date: Dec 2024 --> Dec 2025 | Initiation date: Jun 2023 --> Dec 2023 | Trial primary completion date: Dec 2024 --> Dec 2025
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Biomarker, Journal, BRCA Biomarker, PARP Biomarker: BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor-resistant BRCA-mutant ovarian cancer. (Pubmed Central) - Jun 25, 2023
P2
Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant BRCA-mutant HGSC cells and xenograft mouse models...BRCA reversion mutation in previously PARPi-treated BRCA-mutant patients was not associated with resistance to CHK1i. Our findings suggest that replication fork-related genes should be further evaluated as biomarkers for CHK1i sensitivity in patients with BRCA-mutant HGSC.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Preclinical, Journal, Gram positive, Gram negative: In vitro activity of eravacycline and comparators against Gram-negative and Gram-positive bacterial isolates collected from patients globally between 2017 and 2020. (Pubmed Central) - Jun 20, 2023
This study reaffirms ERV's consistent broad-spectrum activity, which has been evaluated since 2003. ERV remains a key agent for the treatment of bacterial infections, including resistant isolates, but urgent reassessment of clinical breakpoints is required for staphylococci and enterococci.
- |||||||||| aztreonam/avibactam (PF-06947387) / Pfizer, AbbVie, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Clinical, Preclinical, Journal: In Vitro Activities of Aztreonam-Avibactam, Eravacycline, Cefoselis, and Other Comparators against Clinical Enterobacterales Isolates: a Multicenter Study in China, 2019. (Pubmed Central) - Jun 19, 2023
The potent activity of eravacycline against Enterobacterales was higher than that of tigecycline. Cefoselis and cefepime showed a highly consistent activity against Enterobacterales.
- |||||||||| Nuzyra (omadacycline) / Paratek, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Preclinical, Journal: Omadacycline, Eravacycline, and Tigecycline Express Anti-Mycobacterium abscessus Activity In Vitro. (Pubmed Central) - Jun 19, 2023
We found that in vitro MICs of OMC against Chinese and American isolates were distinct. Evaluations in in vivo models of M. abscessus disease or in the clinical setting will provide more accurate insight into potency of OMC against distinct isolates.
- |||||||||| Zerbaxa (ceftolozane /tazobactam) / Merck (MSD), Fetroja (cefiderocol) / Shionogi, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Clinical, Retrospective data, Journal: Comparative efficacy and safety of non-polymyxin antibiotics against nosocomial pneumonia, complicated intra-abdominal infection or complicated urinary tract infection: a network meta-analysis of randomized clinical trials. (Pubmed Central) - Jun 17, 2023
Carbapenems may be preferable options in terms of safety and efficacy for the treatment of gram-negative bacterial complicated infections. However, to preserve the effectiveness of carbapenems, it is important to consider carbapenem-sparing regimens.
- |||||||||| Clinical, Preclinical, Journal: In vitro activities of omadacycline, eravacycline, cefiderocol, apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020-2021: a multicenter study. (Pubmed Central) - Jun 16, 2023
OXA-23-ArmA producing A. baumannii of international clone II appears to be the prevailing epidemiological type of this organism in Greece. Cefiderocol could provide a useful alternative for difficult to treat Gram-negative infections, while apramycin (EBL-1003), the structurally unique aminoglycoside currently in clinical development, may represent a highly promising agent against multi-drug resistant A. baumanni infections, due to its high susceptibility rates and low toxicity.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Preclinical, Journal, Combination therapy: Comparative in (Pubmed Central) - May 22, 2023
strains, including colistin-resistant ones, at 4xMIC of colistin. Although we did not observe synergistic interactions with eravacycline-meropenem or eravacycline-ceftazidime combinations, we did not observe antagonism with any combination tested.This study's findings could have important implications for antimicrobial therapy with tested antibiotics.
- |||||||||| Review, Journal: Steno-sphere: Navigating the Enigmatic World of Emerging Multidrug-Resistant Stenotrophomonas maltophilia. (Pubmed Central) - May 18, 2023
The potential clinical utility of bacteriophage for compassionate use in treating S. maltophilia infections remains to be determined since data is limited to in-vitro and sparse in-vivo work. This article provides a review of available literature for S. maltophilia infection management focused on related epidemiology, resistance mechanisms, identification, susceptibility testing, antimicrobial PK/PD, and emerging therapeutic strategies.
- |||||||||| Review, Journal, Gram negative: Novel Antimicrobial Agents for Gram-Negative Pathogens. (Pubmed Central) - Apr 28, 2023
Furthermore, other agents are in advanced development, having reached phase 3 clinical trials, namely, aztreonam-avibactam, cefepime-enmetazobactam, cefepime-taniborbactam, cefepime-zidebactam, sulopenem, tebipenem, and benapenem. In this present review, we critically discuss the characteristics of the above-mentioned antimicrobials, their pharmacokinetic/pharmacodynamic properties and the current clinical data.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Trial initiation date: Prospective Evaluation of Xerava Prophylaxis in Hematological Malignancy Patients With Prolonged Neutropenia (clinicaltrials.gov) - Apr 26, 2023
P2, N=55, Not yet recruiting,
However, it should be noted that data currently available on the effectiveness, safety, and tolerability of antimicrobial agents pertain mostly to lower-risk patients with cIAIs. Initiation date: Oct 2022 --> Jun 2023
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Preclinical, Journal, Gram negative: Antibacterial Activity of Eravacycline Against Carbapenem-Resistant Gram-Negative Isolates in China: An in vitro Study. (Pubmed Central) - Apr 24, 2023
In addition, the time-kill curves showed that the bactericidal effect of eravacycline was stronger than that of tigecycline against four different types of isolates. Our research indicated that eravacycline had a good antibacterial effect on CRGNB, which could provide a theoretical basis for the clinical treatment of drug-resistant bacterial infections in the future.
- |||||||||| bevantolol (SOM3355) / SOM Biotech
Trial primary completion date: Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - Apr 18, 2023
P2b, N=129, Recruiting,
Our research indicated that eravacycline had a good antibacterial effect on CRGNB, which could provide a theoretical basis for the clinical treatment of drug-resistant bacterial infections in the future. Trial primary completion date: Apr 2023 --> Aug 2023
- |||||||||| Fetroja (cefiderocol) / Shionogi, Mycamine (micafungin) / Astellas, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Acinetobacter Baumanii, the Cloud on the Horizon: A Case of Resistant Infection and Rapidly Progressive Hemodynamic Compromise (Walter E. Washington Convention Center, Area A, Hall C (Lower Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_7925;
We present a case of florid septic shock causing rapid hemodynamic compromise from spontaneous bacterial peritonitis (SBP) secondary to carbapenem-resistant Acinetobacter baumanii (CRAB) in an immunocompromised patient.Case: A 28 year-old female with a history of end-stage renal disease (ESRD) secondary to lupus nephritis on mycophenylate and calciphylaxis on sodium thiosulphate (STS) presented from facility with lethargy after prolonged hospitalization for sepsis secondary to Pseudomonas infection treated with ceftazidime...Peritoneal fluid cell counts suggested SBP, prompting treatment with meropenem...Gentamycin and micafungin were added however the patient further decompensated and expired within 24 hours...Options include cefiderocol, polymyxin B and colistin, minocycline, eravacycline, high dose ampicillin-sulbactam and combinations of these agents in severe infection, guided by sensitivities and organ function. Limited therapeutics and the ubiquity of multi-drug resistant organisms require ICU providers be vigilant in promptly identifying risk factors for infection to avoid sudden and rapid decline in affected patients.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, samotolisib (LY3023414) / Eli Lilly
Trial completion date, Metastases: ExIST: LY3023414 and Prexasertib in Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - Mar 23, 2023
P2, N=10, Active, not recruiting,
Limited therapeutics and the ubiquity of multi-drug resistant organisms require ICU providers be vigilant in promptly identifying risk factors for infection to avoid sudden and rapid decline in affected patients. Trial completion date: Dec 2022 --> Dec 2023
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Preclinical, Journal: In (Pubmed Central) - Mar 20, 2023
This study provides the MIC and susceptibility rate of eravacycline for common Enterobacterales. Eravacycline could be a therapeutic choice for cefotaxime non-susceptible or meropenem non-susceptible Enterobacterales, especially K. oxytoca, C. freundii, and E. coli.
- |||||||||| telaglenastat (CB-839) / Calithera, prexasertib (ACR-368) / Acrivon Therap
Glutaminase inhibition induces replication stress in ovarian cancer cells and inhibition of replication checkpoint causes synthetic lethality (Section 38; Poster Board #14) - Mar 14, 2023 - Abstract #AACR2023AACR_7078;
Furthermore, CB839 and Prexasertib combination was more synergistic in cells that expressed high GLS compared to low GLS-expressing OC cells indicating the specificity of the combination of these drugs. Together, our studies identified a novel connection between metabolic and DNA damage checkpoint pathways in OC and propose a novel synergistic lethality-based combination therapy to treat chemo-resistant and aggressive OC.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
PARG inhibition augments CHK1 inhibitor-induced replication stress and synergistically kills ovarian cancer cells (Section 14; Poster Board #3) - Mar 14, 2023 - Abstract #AACR2023AACR_4889;
Together, these results indicate that this combination treatment cause persistence of heavy PARylation at DNA damage sites abrogates cell cycle checkpoint mechanisms, exhausts cellular NAD+ levels, and inhibits DNA repair leading to the metabolic and mitotic collapse of cancer cells and synergistic lethality in OC cells. Currently, prexasertib is under clinical trials and our studies will provide novel mechanistic insight into the therapeutic potential of this combination and provides preclinical evidence to develop further this combination therapy in treating OC.
- |||||||||| XS-02 / XSXH Therap
Discovery of a novel and oral CHK1 inhibitor for the treatment of solid tumors (Section 17; Poster Board #13) - Mar 14, 2023 - Abstract #AACR2023AACR_2543;
Prexasertib (LY2606368), one of the few agents to undergo clinical trials, specifically inhibits both CHK1 and CHK2, displaying obvious therapeutic effects but also raising inevitable target-associated drug toxicities and a potential compliance issue due to intravenous administration...Moreover, the combination of XS-02 and olaparib, a PARP inhibitor, accelerated tumor regression, which synergy was confirmed in a patient-derived tumor xenograft animal model of acquired resistance to olaparib, without significant body weight changes...These results support the agent as a clinical candidate for the treatment of solid tumors. An Investigational New Drug application is planned for 2023.
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