Lysovant is a clinical-stage anti-infectives biotech company seeking to develop novel therapies for hardest-to-treat drug-resistant bacterial pathogens.

There is an urgent medical need for new strategies to control and treat multidrug-resistant bacterial infections. Lysovant is dedicated to developing novel and non-traditional antibacterial concepts such as phage-derived lysins across both Gram-positive and Gram-negative bacteria.
ABOUT US
Management Team Board Members Scientific Advisors
markus rohrwild headshot

Markus Rohrwild

Interim Chief Executive Officer
kamal hamed headshot

Kamal Hamed

Chief Medical Officer
eric gaukel headshot

Eric Gaukel

Nonclinical Development
kimberly prabhu headshot

Kimberly Prabhu

Clinical Operations
wendy luo headshot

Wendy Luo

Toxicology
shingai majuru headshot

Shingai Majuru

CMC Drug Product
xiao-dong chen hedshot

Xiao-Dong Chen

CMC Operations
george zapf headshot

George Zapf

CMC Regulatory Affairs
marie parrish headshot

Marie Parrish

Regulatory Strategy
brenton smith headshot

Brenton Smith

Program Management
nanxiang ge headshot

Nanxiang Ge

Biometrics & Data Management
gang jia headshot

Gang Jia

Biometrics & Data Management
anja bagutti headshot

Anja Bagutti

Team Coordinator

Markus Rohrwild

Interim Chief Executive Officer

Frank Torti, MD

Vant Chair, Roivant Sciences

Eric Venker, MD

President & Chief Operating Officer, Roivant Sciences
thomas holland headshot

Thomas L. Holland

Associate Professor of Medicine
Division of Infectious Diseases
Duke University School of Medicine
Durham, North Carolina
USA
jose miro headshot

Jose M. Miró

Professor of Medicine
Senior Consultant of Infectious Diseases
University of Barcelona
Barcelona
Spain
david peterson headshot

David Peterson

Professor of Medicine
Consultant Infectious Diseases Physician
University of Queensland
St. Lucia
Australia
steven tong headshot

Steven Tong

Associate Professor of Medicine
Consultant Infectious Diseases Physician
University of Melbourne
Melbourne
Australia
OUR SCIENCE

Tonabacase (LSVT-1701)

Lysovant’s investigational product candidate, Tonabacase (LSVT-1701; previously known as SAL200), is a novel, recombinantly-produced, bacteriophage-encoded lysin. Where other antibiotics and treatments inhibit the synthesis or function of the bacterial cell wall, nucleic acid, membrane, or protein, Tonabacase directly cleaves the bacterial cell wall leading to rapid bacterial lysis.
Learn More
INVESTORS & PARTNERS
intron logo

Tonabacase (LSVT-1701)

Lysovant’s investigational product candidate, Tonabacase (LSVT-1701; previously known as SAL200), is a novel, recombinantly-produced, bacteriophage-encoded lysin. Where other antibiotics and treatments inhibit the synthesis or function of the bacterial cell wall, nucleic acid, membrane, or protein, Tonabacase directly cleaves the bacterial cell wall leading to rapid bacterial lysis.
We believe LSVT-1701 may be the most effective lysin due to its use of two catalytic domains, called amidase and endopeptidase. These domains provide peptidoglycan (cell wall) hydrolysis. While the amidase cuts between the sugar strands and stem peptides, the endopeptidase cleaves the bonds between the stem peptide and the pentaglycine bridge. This novel endolysin mechanism potentially allows for more rapid bactericidal effect. Additionally, endolysin target binding sites are highly conserved and essential to S. aureus bacteria viability. We believe this may contribute to lower propensity for resistance.
bacteriophage encoded lysin image

Image source: Roach et al. (2015); Bacteriophage

Tonabacase is being developed as an adjunctive agent to be combined with standard-of-care antibiotics for the potential treatment of Staphylococcus aureus bacteremia, including infective endocarditis, caused by either methicillin-resistant S. aureus (MRSA) or methicillin-sensitive S. aureus (MSSA). We believe that Tonabacase, if approved for use, could provide the following potential benefits:
  • Rapid antibacterial activity. Where current antibiotic treatments take a long time to suppress the bacteria, Tonabacase has the potential to provide rapid and highly effective lytic action.
  • Genus specificity. Anti-staphylococcal endolysins provide pathogen-targeted bacteriolysis and preserve normal flora.
  • Low propensity for resistance. Target binding sites are highly conserved and essential to bacterial viability.
  • Synergy with standard-of-care antibiotics. Tonabacase has the potential to be used to treat antibiotic-resistant bacteria and administered concurrently with antibiotics.
  • Effective against biofilms. In animal models, Tonabacase eradicated and cleared biofilm where standard of care is ineffective.
  • Effective against all strains. In vitro susceptibility data demonstrate activity against MRSA, MSSA, and multidrug-resistant clinical isolates.
  • Multiple-dose administration. Tonabacase may be administered as multiple doses without dose-limiting toxicity or hypersensitivity in rodents or non-human primates, following single- and repeated-dose toxicology studies.

References:

Jun SY, et al. Antibacterial properties of a pre-formulated recombinant phage endolysin, SAL-1. Int J Antimicrob Agents 2013; 42:156-61.

Jun SY, et al. Preclinical safety evaluation of intravenously administered SAL200 Containing the recombinant phage endolysin SAL-1 as a pharmaceutical ingredient. Antimicrob Agents Chemother 2014; 58:2084-8.

Jun SY, et al. Pharmacokinetics of the phage endolysin-based candidate drug SAL200 in monkeys and its appropriate intravenous dosing period. Clin Exp Pharmacol Physiol 43; 1013-6.

Kim NH, et al. Effects of phage endolysin SAL200 combined with antibiotics on Staphylococcus aureus infection. Antimicrob Agents Chemother 2018; 62:e00731-18.

Huang DB, et al. Efficacy of antistaphylococcal lysin LSVT-1701 in combination with daptomycin in experimental left-sided infective endocarditis due to methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2021; 65:e0050821.

Huang DB, et al. Anti-staphylococcal lysin, LSVT-1701, activity: In vitro susceptibility of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) clinical isolates from around the world collected from 2002 to 2019. Diagn Microbiol Infec Dis 2021; 101:115471.

Tonabacase is a bactericidal bacteriophage-derived biologic candidate with rapid, potent, and selective antistaphylococcal activity via cell wall hydrolysis. Subject to further analysis and confirmation through clinical trials, we believe Tonabacase could provide the following benefits:

  • Rapid Antibacterial ActivityMinutes vs. hours for antibiotics via dual lytic action
  • Synergy with Standard-of-Care AntibioticsDual activity to treat antibiotic-resistant bacteria
  • Effective Against BiofilmsEradicates / clears biofilm unlike standard-of-care antibiotics
  • Genus SpecificityPreservation of normal flora
  • Effective Against All StrainsAntibacterial activity profile against both MRSA & MSSA, and multi-resistant strains
  • Low Propensity for ResistenceTarget binding sites are highly conserved and essential to bacterial viability

Staphylococcus aureus bacteremia and infective endocarditis: burden and significance

Despite the availability of the current antibiotic armamentarium, S. aureus infections, especially those involving the endovascular system (e.g., bacteremia and infective endocarditis, cardiac and hemodialysis device infections, and others), are associated with severe morbidity and high mortality rates. Thus, there is an urgent need for new therapeutic alternatives or adjuncts that utilize novel mechanisms of action for treating S. aureus bloodstream infections, especially left-sided infective endocarditis.
3D render of protein image
Bacteremia is the presence of bacteria in the bloodstream and is a prerequisite for the development of infective endocarditis, which is an infection of the heart’s inner lining or heart valves. Infective endocarditis has an annual incidence of up to 10 per 100,000 of the general population and carries a mortality rate of up to 30% at 30 days. Incidence of S. aureus bacteremia is increasing and is driven by a rise in the numbers of invasive procedures, implanted medical devices, and immunocompromised patients. Complicated cases of infective endocarditis, especially left-sided infective endocarditis, may be accompanied by valvular incompetence, structural destruction (abscess, perforation, fistula formation), heart failure, and are associated with high mortality. S. aureus is the most prevalent cause of infective endocarditis in most studies.

References:

Rajani R and Klein JL. Infective endocarditis: a contemporary update. Clin Med 2020; 20:31-35.

Ahtela E, et al. Occurrence of fatal infective endocarditis: a population-based study in Finland. BMC Infect Dis 2019; 19:987.

Lysovant’s investigational product candidate, Tonabacase, is a novel bacteriophage-derived endolysin. We believe that this product has the potential to be a best-in-class treatment for S. aureus bacteremia, including those with right- and left-sided endocarditis, caused by methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) in patients receiving standard-of-care antibiotics.

lysovant pipeline image
Tonabacase (LSVT-1701) is an endolytic protein with the potential to provide specific activity against Staphylococcus species that was isolated from the SAP-1 bacteriophage. Tonabacase is intended for intravenous administration in a hospital setting.
The Tonabacase clinical development program to date consists of two completed Phase 1 studies in healthy volunteers, a single-ascending-dose study, and a single- and multiple-ascending-dose study in healthy volunteers. In these Phase 1 studies, Tonabacase was found to be generally well-tolerated following a 1-hour intravenous infusion of single doses up to 10 mg/kg and as multiple doses up to 4.5 mg/kg twice daily (i.e., 9 mg/kg daily). All adverse events reported were mild or moderate and included chills or rigors, infusion site reaction, pyrexia, headache, myalgia and fatigue. There were no severe adverse events reported.
A Phase 2, open-label, multiple-ascending-dose study will evaluate the safety, pharmacokinetics, and efficacy of Tonabacase as an add-on to standard-of-care antibiotic therapy for the treatment of complicated MSSA and MRSA bacteremia, including left- and right-sided infective endocarditis.

References:

Wire MB, et al. A Phase 1 study to evaluate the safety and pharmacokinetics following administration of single and multiple doses of the anti-staphylococcal lysin, Tonabacase, in healthy adult subjects. Antimicrob Agents Chemother 2022; 10.1128/AAC.01842-21. Epub ahead of print.

A Phase 1 study to evaluate the safety and pharmacokinetics following administration of single and multiple doses of the anti-staphylococcal lysin, LSVT-1701, in healthy adult subjects

Thirty-two healthy male subjects (8 per cohort) were randomized 6:2 to active:placebo. LSVT-1701, an anti-staphylococcal lysin, was administered intravenously as a 6 mg/kg single dose and as 1.5, 3, and 4.5 mg/kg twice daily for 4 days. LSVT-1701 exposure increased in a greater than dose proportional manner and did not accumulate. Treatment-emergent adverse events (TEAEs) were predominantly of mild intensity. The most common TEAEs were chills, pyrexia, headache, infusion site events, cough, rhinorrhea, and increases in C-reactive protein.
Download article PDF

Efficacy of antistaphylococcal lysin LSVT-1701 in combination with daptomycin in experimental left-dided infective endocarditis due to methicillin-resistant Staphylococcus aureus

We utilized the rabbit model of aortic valve infective endocarditis to examine the combined efficacy of the lysin LSVT-1701 plus daptomycin. The combination of LSVT-1701 plus daptomycin was highly effective at reducing methicillin-resistant Staphylococcus aureus (MRSA) counts in target tissue. When given for four daily doses, both lysin dose regimens in combination with daptomycin sterilized all target tissues. These findings suggest that LSVT-1701 warrants further clinical evaluation as an adjunctive therapy for the treatment of invasive MRSA infections.
Download article PDF

Anti-staphylococcal lysin, LSVT-1701, activity: In vitro susceptibility of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) clinical isolates from around the world collected from 2002 to 2019

LSVT-1701 (previously known as SAL200), is a novel, recombinantly-produced, bacteriophage-encoded lysin that specifically targets staphylococci via cell wall enzymatic hydrolysis. In vitro activities of LSVT-1701 and comparators were tested against 415 Staphylococcus aureus and coagulase-negative staphylococci (CoNS) clinical isolates expressing various resistance phenotypes. The isolates were collected worldwide from 2002 to 2019 and tested for in vitro susceptibility using broth microdilution methodology performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI and EUCAST criteria. MIC90 for all S. aureus, methicillin-susceptible S. aureus, methicillin-resistant S. aureus, and CoNS, were 2 µg/mL. LSVT-1701’s activity was not adversely affected by resistance to antimicrobial comparators against this worldwide collection of S. aureus and CoNS clinical isolates. The results of this study support further clinical development of LSVT-1701 to treat staphylococcal infections, including those caused by multidrug resistant isolates.
Download article PDF

Image source: Farid Ghanbari; Bacteriophage 3D Render

Lysovant empowers a global team of innovators in the biopharmaceutical industry to expand the world of treatable conditions.

With offices in New York City and Basel as well as remote working options, collaborating on a better future together has never been easier.

New York

Lysovant Sciences, Inc.

151 W 42nd Street, 15th Floor

New York, NY 10036

United States

Basel

Lysovant Sciences GmbH

Viaduktstrasse 8

4051 Basel

Switzerland