CLAROMER® Development Programs
Lead Drug Candidate MXB-22,510: This is an extremely broad spectrum anti-infective, effective against all tested pathogens associated with chronic rhinosinusitis. It also has the potential to disrupt the biofilms associated with Long COVID, infectious dementia, and other chronic, unmet medical needs associated with post viral syndromes and brain fungal infections.
Chronic Sinusitis: According to the CDC, chronic sinusitis is suffered by around 12% of the population, causes upwards of $15B in economic costs each year, and 28,000 deaths per year in the US alone. Chronic sinusitis is often caused by combinations of fungal and bacterial infections; and there are currently no approved drugs to effectively cure this kind of infection. It is almost 100% antibiotic resistant. Current treatments for chronic sinusitis are only anti-inflammatory.
Maxwell’s CLAROMER technology produces drug candidates that display extremely broad spectrum efficacy against polymicrobial infections - infections characterized by more than one bacterial and/or fungal pathogens living together in a microbial colony, generally ensconced in a antibiotic-resistant biofilm. Our lead compound has shown high potency against antibiotic-resistant bacteria and fungi, as well as biofilms. Preclinical studies have established the in vitro efficacy of Maxwell’s lead drug candidate against all sinusitis-related pathogens tested to date. And since sinusitis is potentially lethal for immunocompromised patients, the development pathway can take advantage of prioritized FDA human trials which serve to escalate solutions for lethal and completely unmet medical needs.
Universal antimicrobial / Universal antiviral: Several of our platform compounds have activity against 70+ resistant bacteria and all tested fungi. Others are extremely broad spectrum antivirals against all tested strains of Ebola, influenza, and coronaviruses (including MERS, SARS-1, SARS-CoV-2), and some other viruses of future pandemic concern.
Successful Safety Testing
Independent investigators have confirmed that Maxwell’s CLAROMERS® can been tested in animals at over 50x times the therapeutic dose and still cause no toxicity.
These results are important to validate the safety of our compounds at dosage levels way above what would ever be administered for therapeutic purposes.
Subcutaneous
Safety data in mice (confirmed in collaboration with universities and independent labs) show that CLAROMER® brand anti-infectives are were well tolerated in vivo at 1,000 µg/mL concentration when injected under the skin; whereas, preclinical studies indicate activity against airborne viruses starting at 0.220 µg/mL concentration. This data shows a preclinical safety window 4,500 times higher than the effective therapeutic dose tested in skin.
Upper Airway
Safety data in mice (confirmed in collaboration with universities and independent labs) show that CLAROMER® brand anti-infectives are were well tolerated in vivo at the highest levels tested (256 µg/mL concentration) when injected intratracheal; whereas, preclinical studies indicate activity against airborne viruses starting at 0.220 µg/mL concentration. This data shows a preclinical safety window 1,000 times higher than the effective therapeutic dose tested in the upper respiratory system.
Antiviral Mechanism of Action Revealed via Electron Microscope
Figure: Membrane disruption mechanism of action against Herpes Simplex Virus 1 (HSV-1) and SARS-CoV-2 imaged by cryo-electron microscopy at University of Texas Galveston.
Unlike current antiviral drugs, CLAROMER® drug candidates completely destroy a virus as shown here. These stable compounds accurately mimic cathelicidin binding of viral lipids while avoiding human cells. Similarly, they disrupt the viral membrane in a highly specific mechanism, followed by rapid binding of viral DNA and RNA.
You can see efficacy via viral membrane disruption, illustrated here using electron microscopy imaging accomplished at the University of Texas.
Untreated virus on the left. Neutralized virus in the next two columns, with both partially and fully disrupted membranes. Partially disrupted membranes do not exist in nature, illustrating a true mechanism of action study result.
Antibacterial Mechanism of Action Revealed via Electron Microscope
The Claromer technology mimics the mechanism of action of LL-37 very closely. An excellent study on our compounds’ activity compared to LL-37 is published in Nature Scientific Reports. Independent researchers have also performed several animal studies showing that the compounds are able to safely and selectively treat antibiotic resistant bacterial infections in animals.
1) Disruption of Bacterial Cell Wall (Confirmed)
This allows access to the membrane.
2) Disruption of Bacterial Membrane (Confirmed)
The next step is binding and disruption of the bacterial membrane. The compounds target anionic phospholipids like phosphatidylserine in the membrane, and rapidly rip open the membrane, opening a port for more Claromer compounds and immune peptides like LL-37 to enter the bacteria causing internal bacteria fluids to leak out. This is confirmed via electron microscope imaging, soft X-Ray tomography as well as a fractional cell permeabilization study.
3) Binding Bacterial Proteins (Proposed)
Once inside the bacteria, the Claromers bind anionic proteins which halts the bacterial metabolism, effectively killing the bacteria. Electron microscope imaging shows Claromers binding everything inside the bacteria, and all internal motion coming to a stop (bacterial death). However, this requires more study to show detailed imaging of proteins included in the aggregation.
4) Inhibits Bacterial Enzyme Activity (Proposed)
We know that LL-37 is limited in its function by protease enzymes. We also do not see that limitation in Claromer compounds activity. Much lower doses of Claromers are required to rapidly kill bacteria. Enzymes appear to have no effect. However, we have not fully studied how our compounds avoid and inhibit bacterial enzyme activity.
5) Binds Bacterial RNA & DNA (Confirmed)
We know that our compounds rapidly bind bacterial DNA and RNA, which is very important and demonstrates why Claromers do not allow bacteria to develop resistance. This is likely why bacteria have not developed a resistance to the human immune system, because LL-37 also binds bacterial DNA and RNA.
6) Reduces Inflammation (Partially Confirmed)
Like LL-37, Claromers help control inflammation. Unlike LL-37, our lead compounds are only anti-inflammatory. This is confirmed in rat PK/PD studies and in vitro cytokine studies. We believe the Claromers also bind bacterial toxins and acids which are major drivers of inflammation in bacterial infections. Confirmation of toxin binding awaits further study results.
Chongsiriwatana, N.P., Lin, J.S., Kapoor, R., Wetzler, M., Rea, J.A., Didwania, M.K., Contag, C.H. and Barron, A.E., 2017. Intracellular biomass flocculation as a key mechanism of rapid bacterial killing by cationic, amphipathic antimicrobial peptides and peptoids. Scientific Reports, 7(1), pp.1-15.
X-Ray tomography studies were accomplished by the National Center for X-ray Tomography at the Advanced Light Source of Lawrence Berkeley National Laboratory (LBNL).
Figure: PET scan of radioisotope-labeled CLAROMER® compound injected via (A) intraperitoneal, (B) oral, (C) intravenous injections (n=4 for each group).
Pharmacokinetics
Positron emission tomography (PET) images of mice after administration of radio isotope labeled CLAROMER® study compound. A PET scan is an imaging technique using radioactive tracers which appear like a dye on the PET scan images.
Results: The study showed that drug product candidates are excreted in the urine in dose-dependent manner, and are likely processed via the kidney. CLAROMER® brand anti-infective low molecular weight molecules showed general in vivo pharmacological advantages over biologic peptides, including:
High tissue availability (good)
Slower elimination (good)
High in vivo stability (good)
Advanced pharmacokinetics and dynamics, as well as structure activity relationships studies have been accomplished, showing promising results. Results of those studies are available upon execution of a confidentiality agreement.