LPOXY Therapeutics is redefining infection prevention with a novel oral oxygen therapy targeting deadly C. difficile.
Antibiotics are rightly heralded as a cornerstone of modern medicine. They have enabled transformative advances – from organ transplants and chemotherapy to neonatal intensive care and complex surgeries. Yet, antibiotics also carry a hidden cost: the disruption of the human microbiome. This disruption can open the door to opportunistic pathogens, leading to so-called ‘superinfections’ such as yeast vaginitis and Clostridioides difficile colitis, also known as CDI or C. diff.
C. difficile is a spore-forming, anaerobic bacterium that thrives in the absence of a healthy microbiome. It is intrinsically resistant to many antibiotics, making it both difficult to treat and to eradicate. Alarmingly, even successful treatment often doesn’t prevent recurrence; 20% to 60% of patients experience relapses, sometimes multiple. Although new faecal microbiota transplant (FMT) therapies offer some relief, they are only approved for patients who have already survived a first infection.
Preventing CDI remains a major challenge. C. difficile spores persist in hospital environments, resisting antibiotics, disinfectants, heat, and even ultraviolet light. These durable spores are inhaled or ingested, reactivating in vulnerable hosts.
Vaccine development efforts have failed, despite significant investment from major pharmaceutical firms. To date, no vaccine candidate has successfully prevented CDI.
Globally, over 40 billion doses of antibiotics are administered each year, leading to tens of millions of CDI cases. These infections result in tens of thousands of deaths and cost healthcare systems billions. While you may not be aware of it, chances are you know someone who has suffered from this infection.
Colon oxygen: A safe and underexplored solution
C. difficile is killed by the presence of oxygen. This fundamental vulnerability suggests a novel prevention strategy: raising intestinal oxygen levels. Normally, small amounts of oxygen reach the colon via swallowed air and oxygen within food. While average colon oxygen concentration ranges from 0 to 2%, studies have shown colon oxygen levels can transiently reach as high as 20% under natural conditions.
During the early US space programme, experiments demonstrated that human volunteers breathing 100% oxygen at normobaric pressure achieved a colon oxygen concentration of 13%. Today, millions undergo hyperbaric oxygen therapy (HBOT, where patients breathe 100% oxygen) globally for both infectious and non-infectious conditions. These clinical observations affirm that elevated colon oxygen is both common and well tolerated.
Efficacy of colon oxygenation against CDI
Clinical evidence further supports the role of oxygen in suppressing C. difficile. A Russian case report described the successful treatment of pediatric CDI using rectal oxygen insufflation. A larger retrospective study in Japan observed 92 patients being treated for CDI, 16 of whom also received HBOT. Those treated with HBOT recovered faster and had no recurrences, while 22% of the control group experienced relapses. These findings suggest colon oxygen is not only safe but clinically effective.
However, rectal insufflation and HBOT are impractical solutions for large-scale, preventive use.
SIDIPREV™: A scalable, oral oxygen delivery platform
LPOXY Therapeutics, Inc. is developing SIDIPREV™, an orally-administered, enteric-coated capsule designed for co-administration with antibiotics in at-risk patients. Once in the intestine, SIDIPREV™ releases molecular oxygen to prevent CDI before it starts. This oxygen release leverages three scientifically validated mechanisms:
- Direct bacteriostatic toxicity against C. difficile
- Inhibition of toxin production
- Reduction of local inflammation
SIDIPREV™ is a precision medicine – administered only to those patients at times of highest risk: those undergoing antibiotic treatment for infections likely to precipitate CDI.
Clinical trials and regulatory pathway
The safety and tolerability of SIDIPREV™’s active pharmaceutical ingredient (API) have been validated in Phase 1 and Phase 1b clinical trials. LPOXY is now preparing for a pivotal trial in hospitalised, high-risk patients – those receiving high-risk antibiotics for high-risk infections.
LPOXY intends to pursue approval under the FDA’s Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD), a streamlined route established by Congress under the 21st Century Cures Act to accelerate therapies for life-threatening infections in limited populations. The company also plans to apply for Qualified Infectious Disease Product (QIDP) status. This designation provides priority review and extends FDA market exclusivity by five years, potentially protecting SIDIPREV™ in the US through 2045.
A scalable, ESG-friendly business model
SIDIPREV™ is a value-driven product with high margins and a large addressable market. Its low cost of goods enables pricing that will save hospitals money while maintaining healthy margins. Because it is not an antibiotic, SIDIPREV™ avoids the stewardship-driven sales barriers that often hinder anti-infective products. Likewise, it is not a vaccine and is unaffected by vaccine hesitancy. LPOXY anticipates rapid hospital adoption.
Environmentally, SIDIPREV™ is an ESG-friendly solution. It contains no unnatural chemicals that may accumulate in the environment, making it a responsible choice for long-term public health.
Strong intellectual property
LPOXY Therapeutics has built a robust global intellectual property portfolio around the SIDIPREV™ technology, with over 30 issued patents protecting its formulation, mechanism of action, and clinical applications.
Conclusion
C. difficile infection continues to pose a deadly and costly threat to global healthcare. LPOXY Therapeutics’ SIDIPREV™ offers a novel, scalable, and scientifically grounded solution to prevent this stubborn infection. With strong clinical data, a clear regulatory path, and a high-margin, hospital-friendly business model, SIDIPREV™ is positioned to transform the prevention of antibiotic-associated infections worldwide.
Please note, this article will also appear in the 22nd edition of our quarterly publication.
