For decades, infections like gonorrhea and chlamydia were treated as routine; a quick course of antibiotics and life went on. Now, that comfort is collapsing. Neisseria gonorrhoeae has steadily outmaneuvered drug after drug, such as macrolides, fluoroquinolones and more;1 and today we rely on a single injectable, ceftriaxone, in many settings.1 That dependence on one shot exposes how precarious treatment has become.

At the same time, co‑infections with Chlamydia trachomatis are common, and ceftriaxone does not touch chlamydia, so clinicians are forced into combination regimens2 that complicate outpatient care. The result is a dangerous gap. We urgently need effective, preferably oral therapies that can treat both pathogens, or patients will increasingly face hospital‑level care, treatment failures, and preventable long‑term harm.

In addition, recent surveillance also shows concerning shifts in epidemiology and clinical risk. Case counts are rising among younger adults and vulnerable populations,3 while gaps in testing leave many infections undiagnosed until complications arise. Resistant strains are emerging within connected sexual networks,3 where a single treatment failure can seed broader transmission. Compounding the problem, rapid point‑of‑care diagnostics that detect resistance are limited, so clinicians frequently treat empirically rather than based on susceptibility data.3 The result is a convergence of factors: increased incidence, delayed detection, narrowing therapeutic options, and accelerated spread of resistance that elevates routine STIs into complex, costly, and potentially deadly public health challenges.

Beyond Incremental Antibiotic Development

Traditional antibiotic development has frequently involved iterative modifications of existing drug classes. While this approach can yield short-term gains, resistant pathogens such as N. gonorrhoeae rapidly adapt through target mutations, efflux pump overexpression, and other mechanisms.4

Recognizing these limitations, TAXIS Pharmaceuticals has focused on mechanism-driven innovation targeting bacterial processes distinct from commonly used antibiotic classes.

One such approach involves next-generation dihydrofolate reductase inhibitors (DHFRIs).

Why DHFR Matters

Dihydrofolate reductase (DHFR) is essential for bacterial folate metabolism and DNA synthesis. By selectively inhibiting DHFR, it is possible to disrupt bacterial replication through a pathway that differs from fluoroquinolones or beta-lactams.5

Importantly, next-generation DHFR inhibitors are designed with structural modifications intended to retain activity against strains that harbor resistance mutations and to demonstrate activity against intracellular pathogens.5

Advancing TXA16126

TAXIS’ investigational DHFR inhibitor, TXA16126, has demonstrated potent activity in preclinical studies against drug-resistant Neisseria gonorrhoeae. Given the high rate of gonorrhea–chlamydia co-infection, further evaluation assessed its activity against intracellular Chlamydia trachomatis.6

In cell-based studies, TXA16126 inhibited Chlamydia growth at low micromolar concentrations. In contrast, ceftriaxone — the current standard of care for gonorrhea — showed no activity against chlamydia under similar conditions.6

Notably, other investigational agents in development for Neisseria gonorrhoeae have also demonstrated limited or no measurable activity against Chlamydia, highlighting the complexity of developing single-agent solutions for dual-pathogen infections.6

While TXA16126 remains investigational, these findings support continued evaluation of DHFR inhibition as a strategy to address co-infection scenarios and resistant STI pathogens.

A Broader Strategy Against Antimicrobial Resistance

The rise of resistant STIs reflects a broader AMR challenge. Sustainable antimicrobial innovation requires targeting bacterial survival pathways in ways that reduce the likelihood of rapid resistance emergence – not just more “me too” drugs.

TAXIS’ pipeline includes multiple anti-resistance platforms — including DHFR inhibitors, efflux pump inhibitors, and FtsZ inhibitors — each designed to address critical resistance mechanisms in priority pathogens.

By focusing on novel mechanisms and rational drug design, TAXIS aims to expand future treatment options for multidrug-resistant infections, including those affecting men’s reproductive and sexual health.

 

References:

  1. National Library of Medicine. Risk of drug eruption associated with the use of tetracyclines, macrolides, and fluoroquinolones: real-world evidence from a pharmacovigilance study utilizing the FDA adverse event reporting system, January, 2026. National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC12799828/
  2. Mayo Clinic. Ceftriaxone (injection route), January, 2026. Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/ceftriaxone-injection-route/description/drg-20073123
  3. National Library of Medicine. The rising tides of cancers among young adults, September, 2025. National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC12446525/
  4. National Library of Medicine. Neisseria gonorrhoeae Antimicrobial Resistance: The Future of Antibiotic Therapy, 2023. National Library of Medicine https://pmc.ncbi.nlm.nih.gov/articles/PMC10744250/#:~:text=The%20growing%20threat%20of%20antibiotic,and%20Development%20of%20New%20Antibiotics%E2%80%9D.
  5. National Library of Medicine. Chemical Space of Escherichia coli Dihydrofolate Reductase Inhibitors: New Approaches for Discovering Novel Drugs for Old Bugs. September, 2018. National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC6370515/
  6. National Library of Medicine. The frequency of co-infection with Neisseria gonorrhoeae and Chlamydia trachomatis in men and women in eastern Sydney. June, 2010. National Library of Medicine. https://pubmed.ncbi.nlm.nih.gov/8714280/