LPOXY Therapeutics Acquires Assets to Advance C difficile Protection for Antibiotic Patients
CEO Larry D Sutton, MD, PhD, elaborates on the company's strategy and the science behind SIDIPREV to prevent C difficile infections in hospitalized patients.
Larry D Sutton, MD, PhD, CEO of LPOXY Therapeutics
Image credits: LinkedIn
LPOXY Therapeutics, Inc has acquired significant assets from Xeno Biosciences Inc to advance its novel therapy for preventing Clostridioides difficile (C difficile) infections in hospitalized patients. The acquisition includes regulatory filings, FDA correspondence, comprehensive CMC data, and intellectual property from Xeno, as well as data from its Phase I and Ib clinical trials that demonstrate the safety of the shared Active Pharmaceutical Ingredient.
The deal positions LPOXY to progress SIDIPREV, a therapy targeting C difficile, by initiating a pivotal Phase II study under the FDA’s Limited Population Pathway for Antibacterial and Antifungal Development (LPAD). This pathway aims to expedite therapies for serious infections in populations with unmet medical needs. C difficile is a critical public health threat, causing over 80 deaths per day in the US, according to the CDC.
In an exclusive email interview, Larry D Sutton, MD, PhD, CEO of LPOXY Therapeutics, discussed the science behind SIDIPREV and its potential to prevent C difficile infections. Sutton addressed the mechanism of oxygen delivery to the gastrointestinal tract, why SIDIPREV may surpass existing therapies, how LPOXY plans to leverage the FDA’s Limited Population Pathway (LPAD), and strategies to ensure the therapy's widespread use in hospitals.
What is the specific mechanism by which oxygen delivery to the gastrointestinal tract helps prevent C difficile infections?
Image credits: Larry D Sutton, MD, PhD
“In short, C difficile is an anaerobic organism, meaning that oxygen is toxic to it. This toxicity will prevent C difficile infections from taking root. More thoroughly, the effect is multimechanistic as shown in the following figure, where there is the direct toxic effect of oxygen on C difficile and suppression of toxin production (1 & 2). Intestinal oxygen also increases aerotolerant Firmicutes which increases secondary bile acid production which suppresses the germination of C diff spores, has a direct antimicrobial effect on C diff vegetative cells and also suppresses toxins (3, 4 & 5). Oxygen also enhances white blood cell killing of C diff (6) and has a direct anti-inflammatory effect on the intestine (7). Finally, oxygen also increases the population of Clostridium cluster IV, increasing the production of short chain fatty acid which results in an anti-inflammatory effect (8). There is of course literature precident for all of these effects which work together to prevent C difficile infections."
Why does LPOXY believe it will be more effective than existing therapies?
Image credits: Larry D Sutton, MD, PhD
“There are no existing therapies to prevent (primary/first) C difficile infections. Sanofi and Pfizer tried to make vaccines, but failed to meet their primary endpoints in Phase 3. There are approved therapies to treat these infections after they occur and to reduce the rate of recurrences. But SIDIPREV™ is being developed to be administered with antibiotics (the #1 cause of C diff infections) so that people won't get these infections in the first place. The current treatment paradigm and how SIDIPREV™ will change it is shown in the following diagram.”
How will LPOXY navigate the challenges of using the Limited Population Pathway (LPAD) for SIDIPREV in a disease as complex and variable as C difficile infection?
“First let me point out that as you can see in the above figure that if we prevent these infections in the first place, then the disease is no longer complex and variable by definition. Secondly, for LPAD we propose to target elderly patients (≥65 yo) hospitalized for community-acquired pneumonia (CAP) that are being treated with standard antibiotics (fluoroquinolones or ceftriaxone) for CAP. So the patient is high risk for C diff, their infection (CAP) is high risk for C diff, and their antibiotics are high risk for C diff. This fits the FDA definition for LPAD in that we will target a distinct high risk group for which there is no other therapy (to prevent these infections). Another strength of this approach is that we'll run a superiority trial (SIDIPREV vs placebo) unlike antibiotic trials that are usually non-inferiority trials.”
What strategies does LPOXY have in place to ensure that SIDIPREV will be accessible and widely used in hospitals, given the urgent public health threat posed by C difficile ?
“We are currently exploring partnering with pharmaceutical companies that have distriubition channels in place and we have already partnered with a CDMO for manufacturing.”
In conclusion, LPOXY Therapeutics' acquisition of assets from Xeno Biosciences advances the development of SIDIPREV, a therapy for preventing C difficile infections in hospitalized patients. With a clear scientific basis and a focused clinical strategy, LPOXY aims to address this public health issue. As the company progresses through key studies and regulatory pathways, SIDIPREV™ has the potential to change C difficile prevention and improve outcomes for high-risk patients.
Stay tuned for our face-to-face interview with Sutton within the coming days.
