Tackling Antimicrobial Resistance With Precision Targeting
A conversation with Gregory G. Mario and Ajit K. Parhi, Ph.D., TAXIS Pharmaceuticals
TAXIS Pharmaceuticals is developing therapies to combat antimicrobial resistance addressing the root cause of the issue, targeting the foundation of bacterial survival and disrupting the mechanisms that fuel antimicrobial resistance. Life Science Connect’s Michelle Raley caught up with Gregory G. Mario, MBA, president and CEO; and Ajit K. Parhi, Ph.D., chief scientific officer, both of TAXIS Pharmaceuticals, to discuss the company’s approach.
TAXIS recently received a second multimillion-dollar grant from the NIH for your antimicrobial resistance platform. Why is TAXIS focused so intently on antimicrobial resistance (AMR)?
Rather than developing "me-too" drugs, TAXIS targets bacterial mechanisms that enable resistance itself, such as efflux pumps or essential enzymes like DHFR. Our work aims to discover entirely new antibiotic classes and preserve the effectiveness of existing antibiotics to provide durable next-generation treatments. These grant awards reflect more than project-specific merit — they validate our broader strategy: building a diversified portfolio that targets resistance across different mechanisms and pathogens. We now have four clinical-stage or near-clinical candidates, including three with Qualified Infectious Disease Product (QIDP) designation. This momentum allows us to remain agile, scientifically driven, and impact focused.
Do you have any tips for companies hoping to secure NIH funding for AMR research?
Engaging with NIH early — whether through webinars, program officers, or direct queries — can be invaluable for aligning your proposal with evolving agency priorities.
How do WHO’s global AMR priorities influence your strategy?
The WHO’s priority pathogen list is a guiding framework for TAXIS. Our current portfolio targets seven of the top 10 listed threats, including Pseudomonas aeruginosa, Acinetobacter baumannii, and drug-resistant Neisseria gonorrhoeae. These designations help focus our efforts on where they can deliver maximum global impact.
While geopolitical developments — like the U.S. potentially withdrawing from WHO — may alter public health dynamics, the antimicrobial resistance threat is borderless. Our work is informed by a commitment to global health equity, particularly through the development of orally available therapies that can reach underserved populations.
Industrywide in drug development, what needs to happen in terms of early R&D to tackle AMR?
Tackling AMR effectively requires the pharmaceutical industry to shift its R&D approach from incremental antibiotic development toward novel mechanisms of action. Early-stage research must prioritize identifying new druggable targets and employing modern tools like AI-driven screening, structure-based drug design, and high-throughput validation. Crucially, new therapeutics should aim to overcome resistance at the mechanistic level by addressing, for example, efflux pump function or target site modification, rather than relying on variations of existing antibiotic classes.
There also needs to be more robust collaboration between academic institutions, biotech firms, and government agencies to share early data and de-risk development. In a landscape where large pharmaceutical companies have largely retreated from antibiotics, it’s the responsibility of smaller biotech innovators to lead with both scientific rigor and creative discovery models.
TAXIS Pharmaceuticals is developing dihydrofolate reductase inhibitors (DHRIs) and efflux pump inhibitors (EPIs). How is TAXIS addressing the biggest challenge(s) in developing DHRIs and EPIs? Can you tell us more about efforts to minimize toxicity from off-target effects?
For all the drug targets we pursue, ensuring the safety of our molecules is a central focus from the earliest stages of discovery. Our medicinal chemistry strategies are guided by a proactive approach to minimizing off-target effects, beginning with rigorous target validation to confirm that the biological target is directly involved in the disease process and that modulating it will provide therapeutic benefit. We then employ structure-based drug design, using the 3D structure of the target protein to design compounds that bind precisely to the intended site, reducing the likelihood of unintended interactions with other proteins.
These strategies are foundational to both our DHFR and EPI programs. Given the historical challenges around toxicity in EPI development, we apply heightened vigilance in this area. Additionally, our compounds undergo a comprehensive battery of early toxicity screenings, including cytotoxicity, cardiotoxicity, and genotoxicity, to eliminate high-risk candidates before they advance further in the pipeline.
How is TAXIS addressing any challenges associated with oral bioavailability?
Therapeutic delivery at TAXIS is guided by clinical context.
For our EPI candidates — targeted at hospital-acquired and ventilator-associated pneumonia (HAP/VAP) — intravenous administration is essential. In these life-threatening infections, speed and bioavailability are critical; IV delivery ensures rapid and complete systemic exposure, so oral bioavailability is not an issue.
For our DHFRI program targeting super gonorrhea, oral administration is key. It’s about testing and validation. Our lead compound demonstrates 85 percent oral bioavailability, which exactly complements our target product profile for oral use in gonorrhea patients. Oral formulations not only enhance patient adherence and accessibility — especially in low-resource settings — but also support more scalable public health interventions, which is essential in the world of AMR.
What are the next milestones that TAXIS’ preclinical candidates need to hit before IND submission?
EPI Project Milestones/March 2026: We have already demonstrated strong animal efficacy for our EPI-levofloxacin combinations against Pseudomonas aeruginosa infections. Only candidates that passed early toxicity screens without safety concerns have progressed, and these compounds showed no acute toxicity in mice at doses up to 240 mg/kg. The next milestone is to evaluate nephrotoxicity through a multi-day, multi-dose in vivo study in rats, followed by necropsy and histopathological analysis. For longer-term assessments, only two EPI candidates will advance to additional studies in higher-order species. By March 2026, we also aim to complete cardiotoxicity evaluations of our lead candidates in either pigs or dogs.
EPI Project Milestones/March 2027: The top two EPIs will undergo a 14-day repeat-dose toxicity study in Sprague Dawley rats. Data from this study will inform dose selection for a subsequent 28-day GLP-compliant toxicity study, which will assess both the individual EPIs and their combinations with levofloxacin. These evaluations — conducted by CROs under standard GLP protocols — will generate essential data to support clinical administration. Additional preclinical studies, including pharmacokinetics in two species and genotoxicity screening, also will be completed prior to pre-IND discussions. Collectively, these studies will enable both a thorough risk-benefit assessment and the selection of a dosing regimen for entry into human trials.
For the DHFRI program, we aim to complete lead optimization and finalize preclinical candidate selection by April 2026. Subsequent IND-enabling studies will follow, targeting an IND-ready profile in 2028.
As you continue your work to fight antimicrobial resistance, what are your key takeaways for the scientific and global health communities?
Antimicrobial resistance is not just a scientific challenge; it’s a global reckoning. Fighting it demands a radical shift away from incremental antibiotic tweaks and toward disrupting the very biology that enables resistance. Our experience underscores that solving AMR means thinking globally, designing accessibly, and acting urgently — with science grounded in both innovation and equity.