itLysin®

A Game Changer in
Antibacterial Drugs

itLysin® vs. Endolysin

Endolysin is recognized as a solution to the uprising superbugs problem due to its unique ability to specifically lyse the peptidoglycan layer of bacterial cell walls, resulting in cell death. Natural endolysin possess a wide range of applications.

However, through long-time research, iNtRON has found that the application of various technologies such as bioinformatics, protein chemistry, protein engineering, molecular modeling, and bioengineering can enhance functions and existing properties to endolysin.

Combining endolysin properties and these technologies can lead to the development of candidates with higher activity, stability, and performance in the human body.

We can develop new drugs with superior function, efficacy, and safety compared to natural endolysin by engineering endolysin according to various needs. iNtRON named the engineered endolysin, which is the engineered form of natural endolysin, “itLysin®”. Currently we are developing a number of itLysin® pipelines.

Gram(-) Pipelines

Highly Serious Gram Negative Bacterial Infections

Gram-negative bacteria cause infections including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis in healthcare settings. Gram-negative bacteria are resistant to multiple drugs and are increasingly resistant to most available antibiotics. These bacteria have built-in abilities to find new ways to be resistant and can pass along genetic materials that allow other bacteria to become drug-resistant as well.

Most of the antibiotics developed after 1945 were targeting gram positive bacterial infections. Since the 1970s, development for gram negative bacterial infections has been continuing. Nevertheless, a targeted, safe, and effective treatment for gram negative bacteria has yet to be developed. Carbapenem is the current drug of choice for the treatment of gram-negative bacterial infections. While it is a broad-spectrum antibiotic effective against both gram positive and gram-negative bacteria, it is intended to be a drug of last resort and not to be used indiscriminately. Despite this warning, Carbapenem-resistant strains have been reported.

Approximately 965,000 cases of infections are caused by gram-negative bacteria in the United States every year.
Even though innovative drug development is urgently needed, there is no appropriate treatment alternative against gram negative superbugs. Resistance to antimicrobials is a growing crisis in clinical medicine. In 2017, the WHO published a list of bacteria where new antibiotics to tackle them are needed urgently and grouped them according to their priority as critical, high, and medium

Multiple Drug Resistant Acinetobacter Baumannii
Pseudomonas Aeruginosa
Multiple Drug Resistant
Enterobacteriaceae
Carbapenem Resistant
Klebsiella Pneumoniae

GN200 Series Targeting Gram Negative Bacteria - GNA200 · GNK200 · GNP200

iNtRON developed itLysin® GN200 series, next generation novel drugs that are effective against Acinetobacter baumannii,
Peudomonas aeruginosa and Klebsiella pneumonia, by using accumulating bacteriophage endolysin technology and itLysin® technology.

GN200 series show rapid killing of bacteria while preserving normal microflora of the host, and there is unlikely probability of developing resistance.It can also be applied as an effective tool to treat bacterial colony growth called biofilm.

GN200 series is a high-performance, gram-negative, bacteria-targeted, endolysin drug overcoming the existing orthodoxy that endolysin is not effective for bacterial treatment. GN200 has a mechanism of action in which iNtRON's patented material attached to the endolysin penetrates the cell membrane and LPS layer of bacteria, where then the endolysin hydrolyzes the peptidoglycan layer of the gram-negative bacteria (under Horse and Wagon Theory).

GN200 series is divided into GNA200, GNP200 and GNK200 according to the gram-negative bacterial target, and it is expected to have great value as an innovative new drug.

gram cell wall

Gram(+) Pipelines

SAL200 “The World’s First Clinical Trial & Successful First Global Out Licensing Deal”

As the first endolysin bio-drug of iNtRON, SAL200 was developed by utilizing genetic information of bacteriophage, which specifically infects Staphylococcus aureus, and applying genetic engineering and biotechnology. SAL200 has excellent therapeutic effects against antibiotic resistant S. aureus (MRSA, VRSA, VISA) which is the most problematic infectious disease, and it has strong and rapid bactericidal activity.

The SAL200 clinical trial has great significance in that it was the world's first clinical trial of an endolysin-based drug. Solving various difficulties, iNtRON finally made a license deal for SAL200. We will support global clinical trials of SAL200 and actively promote additional license deals for various endolysin pipelines. We will do our best until the endolysin drugs are successfully launched in the market and grow as a blockbuster that can treat many patients suffering from life-threatening infections.

TM_SAL200

TM_SAL200 is an endolysin developed to be administered topically, unlike the systemic administration of SAL200.

iNtRON focuses on chronic topical infection mainly caused by Staphylococcus strains such as impetigo, atopic dermatitis, diabetic ulcer infections and post-operative infection. These types of infections are chronic due to antibiotic resistances. SAL200 does not disrupt the balance of the skin microflora due to SAL200’s specificity targeting solely Staphylococcus strains.

iNtRON has secured the application formulation as topical administration for skin infections through joint development with a U.S. based CDMO company specialized in formulation development.

Other itLysin® Pipelines for Gram(+) Bacteria

We have many other itLysin® Pipelines for Gram (+) bacteria including BAL200, CDL200, and EFL200 as follows.

iNtRON will find and continuously develop various itLysin® pipelines in addition to upper drugs for solving antibiotic resistant problems.
Antibiotic resistance is a crucial problem that humanity must solve. iNtRON will play a pivotal role in solving this antibiotics problem.

BAL200 CDL200 EFL200 SPL200
Target Pathogen Bacillus Clostridioides difficile Enterococci (incl. VRE) Streptococci (incl. S. pneumonia)
Clinical Usage &
Indication
Bacillus infection
(incl. Anthrax)
  • C. difficile
    infection (CDI; AAD)
  • Inflammatory bowel
    disease (IBD)
Enterococci infection
(VRE decolonization; Endocarditis; bacteremia)
Streptococci infection
(incl. Pneumonia)
Administration Route Injection Oral Oral/Injection Injection
Key Characteristics
  • Active against most of B. anthracis strains
  • Broad antibacterial spectrum in Bacillus genus
  • Rapid bacteriolytic activity
  • Active against 100% clinical isolates tested
  • No disturbance of the normal flora
  • Active against 100% VRE clinical isolates tested
  • Rapid bacteriolytic activity
  • Active against 100% vaccine-type and non-vaccine type S. pneumonia strains tested
  • Active against 100% S. pneumonia clinical isolates tested

itLysin® Specific Drug Formulation

We are developing Drug Formulation suitable for each bacterial infection site.

For example, Clostridioides is a bacterium that causes infection of the large intestine (colon). Symptoms can range from diarrhea to life-threatening damage to the colon. For these reasons, we need itLysin® specific formulation for colon including capsules.

Like this, we are developing itLysin® Specific formulations with several companies.

itLysin® Specific Drug Formulation