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Phase 2a Trial Uses Human Milk-Based Therapy for Blood Cancer

MEEFRO November 15, 2023

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The randomized, open-label, multicenter Phase 2a trial will look at the feasibility, efficacy, and safety of combining PBCLN-010 (human milk oligosaccharides [HMOs]) with PBCLN-014 (

]) in adult patients with blood cancers undergoing stem cell transplantation. The experiment will assess how well

integrates into the gut microbiome and other changes in the microbiome over six months to the current standard of treatment. Changes in biomarkers that may predict better patient outcomes will also be monitored by researchers.

“Patients undergoing stem cell transplant often have disruptions in their gut microbiome, including an increase in potentially disease-causing pathogens and an overall loss of diversity. This leaves patients prone to opportunistic infections and graft-versus-host disease, which can result in multi-organ attack and death. This Phase 2a study will measure how well the human milk-based therapy helps establish a healthy microbiome in patients with blood cancers as it does naturally in the newborn gut,” said Karamjeet Sandhu, M.D., assistant professor, Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, one of the largest cancer research and treatment organizations in the United States.

This Phase 2a experiment is part of a larger study on the therapeutic advantages of human milk-based microbiome treatment. The results of two prior clinical trials utilizing this strategy were published in the journal Cell Host & Microbe (May 2022 and September 2023), revealing that PBCLN-010 + PBCLN-014 can manage the gut microbiota in healthy adults safely and predictably (1, 2). This is the first time that such a large change has been induced into a subject’s microbiome, maintained in that subject, and subsequently reversed in healthy adult subjects, demonstrating a high level of control.

The experiment will include prominent stem cell transplant centers from across the country, in addition to the City of Hope in Los Angeles. The company will apply for and expect to receive orphan medication classification based on the severity of the condition and the magnitude of the patient group.

Human Milk Oligosaccharides (HMOs) and Bacillus Infantis

Human breast milk includes significant levels of a group of over 200 structurally different sugars known as human milk oligosaccharides (HMOs) (3). Unlike the nutritious components of breast milk, HMOs are not digested by the newborn as an energy source. Instead, HMOs direct the growth of suitable bacteria in the gut, which aids in the development of the infant’s immune system (4). In this approach, HMOs help guard against infections by suppressing inflammation and improving gut barrier integrity (5).

B. infantis, a kind of “good” bacteria in the infant’s gut known to impact these protective responses, is unusual in its capacity to utilize the HMOs in human breast milk. B. infantis levels in adults decrease once infants are weaned from human milk (6).

Prolacta Bioscience, a privately held worldwide life sciences firm dedicated to Advancing the Science of Human Milk, provided research, development, and early clinical trial support for PBCLN-010 and PBCLN-014. The company is currently looking for strategic partners to help it continue development and pursue therapeutic market prospects.

References:

Button et al. Precision modulation of dysbiotic adult microbiomes with a human-milk-derived synbiotic reshapes gut microbial composition and metabolites. Cell Host Microbe. 2023;31:1-16. doi: https://doi.org/10.1016/j.chom.2023.08.004

Button JE, et al. Dosing a synbiotic of human milk oligosaccharide and B. infantis leads to reversible engraftment in healthy adult microbiomes without antibiotics. Cell Host Microbe. 2022;30(5):712-725. doi:10.1016/j.chom.2022.04.001

Moukarzel S, Bode L. Human milk oligosaccharides and the preterm infant: a journey in sickness and in health. Clin Perinatol. 2017;44(1):193-207. doi:10.1016/j.clp.2016.11.014

Wicinski M, Sawicka E, Gebalski J, et al. Human milk oligosaccharides: health benefits, potential applications in infant formulas and pharmacology. Nutrients. 2020 Jan;12(1):266. doi: 10.3390/nu12010266 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019891/

Chichlowski M, Shah N, Wampler JL, et al. Bifidobacterium longum subspecies infantis (B. infantis) in pediatric nutrition: current state of knowledge. Nutrients. 2020 Jun;12(6):1581. Published online 2020 May 28. doi: 10.3390/nu12061581 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352178/

Arboleya S, Watkins C, Stanton C, et al. Gut bifidobacteria populations in human health and aging. Front Microbiol. 2016;7:1204. Published online 2016 Aug 19. doi: 10.3389/fmicb.2016.01204 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990546/