Synedgen Announces Gut Microbes Publication of Preclinical Data Showing MIIST305 Mitigates Gastrointestinal Acute Radiation Syndrome Injury in a Murine Model

CLAREMONT, Calif., February 26, 2025 – Synedgen, Inc., a biotechnology company targeting
human glycobiology to treat gastrointestinal diseases, today announced the publication of
preclinical data that shows MIIST305 mitigating gastrointestinal acute radiation syndrome (GI-ARS)
injury and ameliorating radiation-induced gut microbiome dysbiosis in a murine model. The paper
has been published in Gut Microbes and is coauthored by Synedgen and its research
collaborators at Columbia University’s Center for Radiological Research. You can read the full
article here.

“In our study, MIIST305 greatly enhanced the survival of mice exposed to lethal radiation and
protected the GI tract from injury by restoring a balanced gut microbiota and effectively reducing
proinflammatory responses,” said Dr. Constantinos G. Broustas, Associate Professor of Radiation
Oncology (in the Center for Radiological Research) at Columbia University Vagelos College of
Physicians and Surgeons. “Based on this and other data, further development of this drug is
warranted, especially given the lack of FDA-approved countermeasures to treat GI-ARS.”

High-dose radiation exposure is known to result in gastrointestinal (GI) acute radiation syndrome
injury and currently there are no FDA-approved countermeasures that can treat this condition. To
meet this unmet need, Synedgen has developed a glycopolymer radiomitigator (MIIST305) that is
specifically targeted to the GI tract and acts by intercalating into the mucus layer and the glycocalyx
of intestinal epithelial cells that can potentially ameliorate the deleterious effects of radiation.

In this preclinical study, male C57BL/6J adult mice were exposed to 13 Gy partial body X-irradiation
with 5% bone marrow shielding. MIIST305 was then administered on days 1, 3, and 5 post-irradiation.
Approximately 85% of the animals survived the irradiation exposure and were apparently healthy
until the end of the 30-day study period. In contrast, no control, vehicle-treated animals survived
past day 10.

MIIST305 improved intestinal epithelial barrier function and suppressed systemic inflammatory
response mediated by radiation-induced pro-inflammatory cytokines. Furthermore, taxonomic
profiling and community structure of the fecal and colonic mucosa microbiota demonstrated that
MIIST305 treatment increased microbial diversity and restored an abundance of beneficial
commensal bacteria, including Lactobacillus and Bifidobacterium genera, while suppressing
potentially pathogenic bacteria compared with vehicle-treated animals.