TAXIS Pharmaceuticals is researching new classes of anti-resistance agents that employ novel mechanisms of action.

We are focusing our science on the disruption of the foundation of bacterial cell wall architecture — including construction, maintenance, and growth — to address elemental drug resistance mechanisms. Here are some of the most promising treatments in our current pipeline.

TAXIS Pharmaceuticals currently has three investigational therapies in our pipeline:

  1. FtsZ inhibitors are a class of compounds that target the bacterial protein FtsZ, which plays a crucial role in cell division. By disrupting FtsZ function, these inhibitors prevent the formation of the bacterial cell’s division machinery, ultimately inhibiting bacterial growth and reproduction.
    More about FtsZ inhibitors.
  2. Efflux Pump Inhibitors (EPIs) which represent a new drug class against Gram-negative multidrug-resistant (MDR) pathogens.
    More about Efflux Pump Inhibitors.
  3. Dihydrofolate Reductase Inhibitors (DHRIs) which  block the activity of the enzyme dihydrofolate reductase, essential for bacterial and human cell growth.
    More about Dihydrofolate Reductase Inhibitors.

FtsZ Inhibitors

FtsZ inhibitors are a class of compounds that target the bacterial protein FtsZ, which plays a crucial role in cell division. By disrupting FtsZ function, these inhibitors prevent the formation of the bacterial cell’s division machinery, ultimately inhibiting bacterial growth and reproduction. This approach represents a promising strategy for developing new antibiotics to combat.

TXA709 – Our First Ftsz Inhibitor Candidate

  • TXA709, TAXIS’ lead product candidate, is a novel target – first-ever product to target FtsZ proteins.
  • Oral anti-MRSA agent that completed a Phase I clinical trial with no serious adverse events.
  • Ongoing research focuses on disrupting bacterial cell wall architecture to address drug resistance mechanisms.
  • TXA709 is developed as an anti-resistance drug for combination therapy with obsolete antibiotics.
  • Targets the FtsZ bacterial cell division protein, offering potential for future development against Gram-negative bacteria.
  • Designated a Qualified Infectious Disease Product (QIDP) by the FDA in September 2016.
  • Regulatory incentives include eligibility for Fast Track designation, priority review, and extended marketing exclusivity under the GAIN Act.
How TXA709 – Our First Ftsz Inhibitor Candidate - works

Efflux Pump Inhibitors

Bacterial efflux pumps, which function like bilge pumps, play a central role in making bacteria resistant to antimicrobials due to their unique ability to expel a variety of structurally diverse compounds from the internal cellular environment to the exterior. In addition to expelling antimicrobials, efflux pumps are crucial for bacterial stress responses and virulence. These pumps are recognized as critical antimicrobial resistance determinants in many Gram-negative bacteria. Targeting bacterial efflux pumps with efflux pump inhibitors (EPIs) has the potential to rejuvenate the antibacterial drug discovery pipeline by preventing antibiotics from being eliminated from bacterial cells.

The first-in-class use of EPIs as adjuvants could help address the antibiotic resistance problem in multiple ways, including restoring the efficacy of older antimicrobials and minimizing the emergence of bacterial resistance. Additionally, utilizing EPIs reduces the need to discover new antibiotics, saving significant time, effort, and capital associated with antibiotic discovery and development.

Although the adjunctive application of EPIs in antimicrobial chemotherapy is not a new approach, the observed toxicity of earlier developed EPI classes has been a major impediment to their clinical use. Currently, their applications are mainly restricted to epidemiological studies.

Our novel EPIs distinguish themselves by their significant potential as first-in-class combination therapies against Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP) due to the following salient features:

  • Adjunctive application of our EPIs can revive the effectiveness of multiple classes of antibiotics (28 currently approved and marketed) that are either ineffective or require high doses to overcome diminished activity.
  • They exhibit strong potentiation of levofloxacin and other antibiotics against more than 600 multidrug-resistant (MDR) clinical isolates of P. aeruginosa, with 16 of the current treatment options showing no effect against these isolates except for the toxic drug colistin.
  • They demonstrate no indications of inherent or combination toxicity, circumventing the major limitation of previously developed EPIs.
  • They are efficacious in vivo, potentiating levofloxacin in murine models of lung and thigh infections caused by P. aeruginosa, thereby achieving a critical milestone in translating these combination therapies from the lab to clinical settings.
Efflux Pump Inhibitors - how they work schematically

Dihydrofolate Reductase Inhibitors (DHFRIs)

The clinical success of trimethoprim (TMP) demonstrates the potential of targeting the bacterial Dihydrofolate Reductase (baDHFR) enzyme. However, bacterial DHFR inhibitors have not been effective against Neisseria gonorrhoeae (Ng) because of its natural resistance to TMP, which is caused by a reduced affinity of the enzyme for the drug.

With existing antibiotics proving ineffective and the rise of ceftriaxone-resistant strains threatening the last line of defense, Ng has been designated as a priority pathogen by the World Health Organization (WHO).

TAXIS DHFR inhibitors (TDHFRIs) represent a promising new class of drugs that can address multi-drug-resistant gonorrhea infections. They offer several key advantages:

  • High selectivity for baDHFR, which reduces the risk of toxicity from off-target effects, and a narrow-spectrum antibacterial activity, minimizing the impact on the microbiome.
  • Excellent oral bioavailability, providing a more convenient and cost-effective alternative to the current standard treatment, injectable ceftriaxone.
  • Strong efficacy against drug-resistant strains at nanomolar concentrations, with no pre-existing resistance.
  • Complete eradication of Ng infections in a mouse model of vaginal tract infection following oral administration.
TAXIS DHFR inhibitors (TDHFRIs) represent a promising new class of drugs that can address multi-drug-resistant gonorrhea infections. This image shows how they act.