DEVELOPMENT PROGRAM IBP-9414

IBP-9414 contains the active ingredient Lactobacillus reuteri, which is a human bacterial strain found naturally in breast milk. Lactobacillus reuteri is a live bacterium known to be anti-inflammatory, anti-pathogenic, and beneficial for intestinal motility and maturity of intestinal mucosa. All of these factors contribute to the prevention of NEC, which is characterized by severe inflammation and pathogenic activity, as well as inhibition of intestinal motility and maturation (see images below). IBP-9414 is formulated with the vulnerable target group of premature infants in mind.

IBT received orphan drug designation from the FDA for L. reuteri for the prevention of NEC in premature infants in 2013 and from the European Commission in 2015. IBT received Rare Pediatric Disease designation for IBP-9414 from the FDA in 2016.

In June 2016, IBT initiated a safety and tolerance study. At the end of 2017, the results from the study showed a similar safety and tolerance profile in both the active group and the placebo group.

In November 2018, following discussions with the FDA, IBT decided to modify the protocol for the Phase III study for IBP-9414, which aimed to prevent necrotizing enterocolitis (NEC) in premature infants. In accordance with FDA guidance, IBT amended the protocol to allow for additional treatment areas, such as shortening the time it takes for infants to be able to thrive on the food they eat. In our clinical study, we measured this ability as “sustained feeding tolerance” (SFT).

The pivotal Phase III study, “The Connection Study,” was initiated in 2019, and the first patient was recruited in July 2019. In December 2021, a blinded evaluation was presented showing that even a reduction in the time to SFT correlates with fewer complications such as sepsis and bronchopulmonary dysplasia, a chronic lung disease that affects premature infants.

In April 2024, the last patient was recruited into The Connection Study, and in July 2024, the last patient in the study completed treatment. In August 2024, IBT received the results of the study, which showed that the group treated with IBP-9414 had a significant reduction in total mortality of 27% compared to the placebo group, meaning that widespread use of IBP-9414 could save more than 1,000 patients annually in the US alone.

The treatment has been designated both a “Breakthrough Therapy” (March 2025) for gastrointestinal mortality and a “Rare Pediatric Disease,” reflecting its potential to meet a significant unmet medical need.

IBT’s plan is to apply for marketing approval in the US in 2026 through an accelerated application. As the development program for IBP-9414 is Breakthrough Designated, IBT has the option of submitting the marketing authorization application in several parts instead of all at once, which we intend to do.

The clinical documentation was submitted to the FDA in 2025. IBT will continue the documentation of the clinical effects of IBP-9414, with a focus on its ability to reduce mortality in premature babies. IBT has agreed with the FDA that IBT will develop a proposal for a study that the company intends to conduct after the launch of IBP-9414. IBT intends to submit this proposal, together with validation of the production process for manufacturing commercial volumes of IBP-9414 and other relevant documents, in 2026.

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Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a leading cause of death among premature infants in neonatal intensive care units (NICU). NEC annually kills approximately 3,700 and 1,500 infants annually in Europe and the US, respectively. NEC has an unpredictable, spontaneous, and acute onset and major surgery is today the only specific treatment available. NEC is a serious inflammatory disease of the newborn bowel in which portions of the bowel undergo tissue death (necrosis).

The long-term clinical consequences for infants who survive NEC are variable and include short bowel syndrome, parenteral nutrition-associated cholestasis, abnormal growth, and adverse neurodevelopmental outcomes, including cerebral palsy, cognitive impairment, visual impairment, and hearing impairment.

Clinical Experience

IBT has contributed to the clinical relevance of the Lactobacillus reuteri research field by completing its own Phase II safety and tolerability study. It found that IBP-9414 was safe and well tolerated by premature infants with birth weights between 500 and 2000 grams.

The doses studied in the completed Phase 2 study were 1 × 108 colony-forming units (CFU) and 1 × 109 CFU of L. reuteri. IBP-9414 was administered to subjects in doses once daily for 14 days in the completed Phase 2 study.

It was a randomized, double-blind, parallel-group, dose-escalation, placebo-controlled, multicenter study that investigated the safety and tolerability of IBP-9414 administered to premature infants weighing between 500 and 2000 g.

IBT has also completed a Phase III study in 2158 premature infants – The Connection Study.

This was a randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of IBP-9414 in premature infants with a birth weight of 500 to 1500 g. In this study, only 1 dose of L. reuteri (1 × 109 CFU) was studied for up to 11 weeks and 6 days.

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