[Photo and Text by E-Daily Reporter KIM JI-WAN ] “Telling patients with fishy odor syndrome not to eat eggs or meat is not a realistic treatment. People have to eat to survive.”

These were the first words heard during an exclusive interview conducted on the 22nd by Pharm eDaily—eDaily’s premium pharmaceutical and biotech content platform—with Yoon Sang-sun, CEO of BioMi and Professor (M.D.) in the Department of Microbiology at Yonsei University College of Medicine.

A Paradigm Shift: Eliminating Trimethylamine

While explaining “BM109,” a candidate drug for treating the rare disease trimethylaminuria (TMAU), CEO Yoon emphasized, “There are limitations to the approach of avoiding the cause of the disease,” adding, “The key is to directly eliminate the causative substance produced in the gut.”

Biomi’s trimethylaminuria treatment candidate, BM109, has received approval for an Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) and is set to begin clinical trials in earnest. This clinical trial will be conducted at Yale University Hospital and the Mayo Clinic in the United States, involving 16 patients with trimethylaminuria. Given the nature of this rare disease, there will be no placebo group; the primary endpoints are a reduction in trimethylamine (TMA) in urine and an improvement in quality of life.

He stated, “Since BM109 is derived from human-origin microorganisms, it significantly reduces the burden of toxicity testing, and we have received FDA approval to administer the drug directly to patients,” adding, “After confirming its efficacy in patients with fish-odor syndrome, we plan to expand its indications to include chronic kidney disease (CKD) and cardiovascular disease (CVD).”

Fish-odor syndrome is a rare condition in which TMA—produced when gut microbes break down choline, carnitine, betaine, and lecithin found in food—is excreted through sweat, urine, and breath, causing a smell reminiscent of rotting fish. The problem is that the components that serve as raw materials for TMA are widely present in everyday diets.

Although patients strive to maintain a low-choline diet, its effectiveness is known to be limited. This is because various foods—such as eggs, meat, fish, and legumes—can serve as precursors for TMA production.

CEO Yoon stated, “If alcohol were the problem, abstaining or cutting back would suffice, but fish-odor syndrome isn’t that simple,” adding, “Restricting food intake itself can further lower patients’ quality of life.”

The suffering of patients with fishy odor syndrome goes beyond a simple body odor issue. Since the odor does not go away, many patients avoid social interactions and face difficulties at work or school.

He explained, “I receive emails directly from patients overseas,” noting, “Many told me they had seen countless doctors but couldn’t find one who understood their condition.” He added, “This isn’t a problem that can be solved with perfume or a shower, because TMA is continuously produced and excreted from within the body.”

The solution chosen by Biomi is not dietary restriction but “removal of TMA from the gut.” When food enters the gut, existing gut microbiota produce TMA, and the administered BM109 then breaks down this TMA within the same gut environment. In other words, it creates a cycle: “food → gut microbiota → TMA production → TMA removal by BM109.”

CEO Yoon explained, “The idea is that if we cannot completely prevent TMA from being produced, we should simply remove it right where it is produced,” adding, “BM109 is a therapeutic agent that directly breaks down the causative substance in the gut.”

Complete Breakdown of Trimethylamine Using 11 Enzymes

BM109 is different from what are commonly referred to as probiotic products. Since it does not consist of bacteria that produce lactic acid, it cannot be developed as a dietary supplement; rather, it is a live microbial therapeutic agent that must be developed as a pharmaceutical product.

He explained, “BM109 is cultured at high concentrations, then freeze-dried to produce the active pharmaceutical ingredient (API), and finally formulated into oral capsules,” adding, “According to the clinical protocol, it is designed to be taken twice daily, 30 minutes before breakfast and dinner.” Chong Kun Dang Bio is responsible for the production of the clinical-grade therapeutic agent. The process involves establishing a master cell bank and a working cell bank based on the bacterial strain, followed by cultivation, freeze-drying, and formulation.

The metabolic pathway that breaks down TMA is considered the core of BM109. According to CEO Yoon, BM109 possesses 11 enzymatic pathways that metabolize TMA into carbon dioxide and other compounds. Among the countless microorganisms present in feces, strains with such a highly developed TMA degradation pathway are extremely rare.

CEO Yoon stated, “It was a great stroke of luck that we were able to isolate BM109,” adding, “While most people’s intestines contain microorganisms that produce TMA, there aren’t many that can sufficiently break it down. By mass-cultivating BM109 and administering it as a medication, we can achieve the goal of reducing TMA levels in the gut.”

Its differentiation from competing technologies is also clear. Some companies are developing strategies to inhibit TMA-producing enzymes using small-molecule drugs. However, small-molecule drugs have the potential to be absorbed systemically. In contrast, BM109 remains in the gut, directly removing TMA that has already been produced and subsequently excreting it in feces.

CEO Yoon emphasized, “While blocking the TMA-producing enzyme is one approach, BM109 breaks down the TMA produced in the gut itself,” adding, “It is a much more mechanism-oriented approach in that the target and site of action are clearly defined.”

Beyond Rare Diseases to Kidney Diseases

Biomi’s expectations for BM109 extend beyond the treatment of fish-odor syndrome. CEO Yoon Sang-seon has set his sights on chronic kidney disease as the next target.

Trimethylamine N-oxide (TMAO) is identified as the key link. TMAO is a substance produced when TMA, generated by gut microbiota, undergoes a further conversion within the body. In healthy individuals, this process converts malodorous TMA into virtually odorless TMAO, preventing the characteristic rotten fish odor. In contrast, patients with fish-odor syndrome have a malfunction in this process; TMA is not fully processed and is excreted through sweat, urine, and breath, causing a distinctive foul odor.

Recently, TMAO has been gaining attention not merely as a substance associated with odor, but as a factor that can exacerbate chronic kidney disease and cardiovascular disease. In particular, a series of studies has shown that when kidney function declines, TMAO is not properly excreted in the urine and accumulates in the bloodstream; this accumulated TMAO promotes fibrosis—a process that causes kidney tissue to harden—leading to a vicious cycle that further worsens kidney function.

He explained, “TMAO is known to be associated with atherosclerosis in blood vessels and to induce fibrosis in the kidneys,” adding, “The goal of BM109 is to remove TMA from the intestines, thereby reducing TMAO production itself.”

However, BM109 is intended to be developed as an adjunct therapy rather than a replacement for existing chronic kidney disease treatments. Currently, patients with chronic kidney disease primarily use medications to control blood pressure or reduce the burden on the kidneys; the plan is for BM109 to complement these treatments by lowering TMAO, a harmful metabolic byproduct in the blood.

CEO Yoon stated, “While existing treatments physically protect the kidneys, BM109 works on the principle of chemically protecting the kidneys by reducing the burden of toxic metabolites,” adding, “Another advantage is that it can be used in conjunction with existing medications because it acts within the gut and is then excreted from the body.”

“Global Interest Continues to Grow” Interest

from global pharmaceutical companies is also growing. He said, “We have been in discussions with overseas pharmaceutical companies since last year and have signed confidentiality agreements (CDAs) with some of them,” adding, “In particular, some companies view BM109 as a new technology that can be utilized in the treatment of chronic kidney disease.”

Biomi’s strategy is to begin with clinical trials for fish-odor syndrome and subsequently expand its indications to chronic kidney disease and cardiovascular disease. This amounts to a platform strategy of tackling multiple diseases with a single microbial therapeutic.

Preparations for commercialization are also gaining momentum. Starting this fall, the company plans to launch a Named Patient Program (NPP) in collaboration with the UK-based BAP Pharma. This program allows for the limited supply of new drugs—even those that have not yet received formal approval—to patients for whom no suitable treatment is currently available.

CEO Yoon explained, “Patients with rare diseases often have very few treatment options,” adding, “Through the NPP, we plan to provide treatment opportunities to actual patients while simultaneously accumulating clinical experience and data.” Based on this, the company intends to pursue a technology evaluation and an initial public offering (IPO) in the future.

He emphasized, “Until now, many microbiome companies have stuck to a somewhat abstract approach—that ‘increasing beneficial bacteria is good for health.’ What sets Biome apart is that it presents a clear mechanism that directly targets and eliminates TMA, the key causative agent of disease.”

He went on to express his aspirations, stating, “BM109 will not be limited to simply being a treatment for fish-odor syndrome,” and added, “Ultimately, we will develop it into a new treatment option that improves the health of patients with chronic kidney disease and cardiovascular disease, thereby proving our competitiveness in the global market.”