Bodhecom Therapeutics: Leveraging Physics to Crack Immunology's Toughest Challenge

Hundreds of millions of people worldwide suffer from autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and lupus. They all face a common dilemma: existing drugs either suppress the immune system insufficiently or over-suppress it, leading to a sharp increase in infection risks. What is truly lacking is "precise braking," rather than a complete shutdown. In 2025, the Nobel Prize has brought this field into the spotlight. Meanwhile, in China, Professor Yan Shi from Tsinghua University and Benerhera, the company he founded, have been quietly advancing on this path for nearly five years. They have just received FDA approval to begin clinical trials, with BT-101 becoming one of the world's first orally administered small-molecule drugs designed to induce Tregs in the human body.

On April 18, after a light rain, Boston was tranquil and serene.

The 2026 American Association of Immunologists Annual Meeting (IMMUNOLOGY 2026) is being held in this city, lasting for five days. Cue Biopharma announced in advance on the opening day that it would present the latest in vivo data of its candidate drug CUE-401 today during the poster session of the conference. At this moment, this presentation is underway.

Immunologists from around the world gathered around poster boards, discussing cellular data from animal experiments. Cue Biopharma's CUE-401, a bifunctional fusion protein that combines TGF-β and IL-2 mutein, aims to induce FOXP3+ regulatory T cells (Treg) and shut off the inflammation switch at its source.

To be honest, there aren't many people stopping in front of his poster. But if you know about the Nobel Prize and are familiar with the autoimmune direction, you will understand what this technical route means.

More importantly, across the ocean, there is a Chinese company called Benerhera, which is doing something even more groundbreaking in the same field.

The Night the Nobel Prize Was Announced

Let's go back to October 6, 2025.

Stockholm's Karolinska Institute Announces: The 2025 Nobel Prize in Physiology or Medicine Awarded to American Scientists Mary E. Brunkow, Fred Ramsdell, and Japanese Scientist Shimon Sakaguchi for Their Discovery of Regulatory T Cells and Their Central Role in Peripheral Immune Tolerance.

These three names are not unfamiliar in the immunology circle, but for most people, they are still three unfamiliar faces.

In 1995, Shimon Sakaguchi discovered a situation that was inconsistent with the mainstream understanding at the time: while the entire academic community believed that immune tolerance only occurred in the thymus (central tolerance), he discovered another group of cells that specifically played the role of police in peripheral tissues, monitoring other immune cells and preventing them from attacking their own tissues. He later named this group of cells regulatory T cells (Treg).

In 2001, Brunkow and Ramsdell discovered the FOXP3 gene: mutations in this gene cause severe systemic autoimmune disease in mice. The corresponding mutation in humans leads to IPEX syndrome, a fatal multi-organ autoimmune disease. Two years later, Shimon Sakaguchi demonstrated that FOXP3 is the master gene controlling Treg development and function.

Thirty years of efforts have won a Nobel Prize, and also brought about a re-pricing of the entire industry.

On the day the Nobel Prize was announced, Dr. Liu Feng, Chief Operating Officer (COO) of Benerhera, was attending a friend's gathering. That night, his mobile phone was almost constantly in his hand. After the news was confirmed, he described his feelings this way: surprised and also excited. Surprised because the Nobel Prize came sooner than they had anticipated; excited because this field, once considered by many as an unconventional and niche track, has finally received attention at the highest level of the global academic community.

An "Accidental" Discovery Under the Atomic Force Microscope

To talk about Benerhera, we must first get to know Shi Yan.

Shi Yan is a doctoral supervisor at the Institute of Immunology of Tsinghua University, with a background in immunology, but he has done something extremely rare among immunologists:Using tools from physics to examine the behavior of immune cells across disciplines.

In 2007, Shi Yan started with atomic force microscopy technology and developed a single-cell force spectrometer. The core capability of this instrument is to precisely measure the physical interactions between cells, with precision down to the piconewton level.

The purpose of the experiment, at first, was not Treg.

But during one measurement process, they captured an anomalous signal:The binding force between Treg cells and dendritic cells (DCs) far exceeds the interaction between ordinary T cells and DCs."We used a machine that studies crystals to observe regulatory T cells (Treg) and accidentally found that Tregs exhibited significant strong adhesion properties when in contact with dendritic cells," Shi Yan once said.

It was an accident. But Shi Yan didn't let it go.

In the nearly twenty years of research that followed, his team systematically dissected the core molecular mechanisms by which Tregs exert their immunosuppressive effects, building on this discovery:Treg cells directly block DCs from presenting antigens to effector T cells by enhancing specific adhesion with DCs, cutting off the initiation of inflammatory signals at the source.They also precisely identified the key signaling pathways and regulatory targets in this process. In 2023, they published a paper in JCI Insight, using the RyR2-Ca²⁺ oscillation pathway to explain the molecular key to this "brake."

This is not following the Nobel Prize. It is a parallel and deeper path.

Shimon Sakaguchi discovered Tregs. Yan Shi's team, from the perspective of cellular mechanics, answered the question of what mechanism Tregs use to "apply the brakes"—a question Sakaguchi had not addressed.

In December 2021, encouraged by Tsinghua University, Shi Yan founded Benerhera with these achievements.

Three Drugs, Three Bets

After years of development, Benerhera currently has three pipelines, each of which is transforming the Treg mechanism into products in different ways.

BT-101: Oral small molecule that recruits Treg from the gut

This is the company's fastest progressing pipeline, and also the world's first oral small molecule drug targeting the in vivo induction of Treg generation.

Its mechanism of action is quite ingenious: by activating specific G protein-coupled receptors (GPCRx) in the intestinal immune system, it promotes dendritic cell function, thereby inducing naïve T cells to differentiate into FOXP3+ regulatory T cells in vivo, effectively applying the "brakes" of the immune system from within.

The first indication is Inflammatory Bowel Disease (IBD). This is not a response to trends but a mechanism-driven choice. Dr. Liu Feng once said that since it takes effect in the gut, the selection of indications must strictly align with the mechanism and not blindly follow trends. This is not just rhetoric; IBD is precisely the most classic site for the occurrence of oral immune tolerance, and BT-101’s induction logic is highly compatible with the gut microenvironment.

On January 14, Benerhera announced: BT-101 has received FDA Investigational New Drug (IND) approval, officially launching the first-in-human trial (FIH) to evaluate safety, tolerability, and pharmacokinetics (SAD/MAD design) in healthy subjects.

This is the world's first orally administered small-molecule drug for in vivo Treg induction to enter human trials. Period.

BT-201: Topical Small Molecule, Letting the Skin Grow Its Own Brakes

If BT-101 is the oral version, then BT-201 is the topical version—the world’s first small-molecule topical formulation targeting the core immunosuppressive pathway of Tregs, used for autoimmune skin inflammatory diseases.

On October 27, 2025, Benerhera and Ruipu Bio-Tech (300119), a leading company in the animal health sector, officially announced a strategic partnership. The two parties will jointly carry out global research, registration, and commercialization of BT-201 in the animal health field. The total value of the collaboration is expected to set a new record for technology licensing transactions in China's animal health industry.

Some people may think: Working on pet skin diseases? Is this a step down?

On the contrary. This is an extremely smart move. The regulatory pathway for animal health is shorter, with faster commercialization speed. It allows verification of core mechanisms and accumulation of clinical data under lower risk, while building brand recognition in global channels: reducing the cost of validating the platform from the hundreds of millions of dollars typical for human clinical trials to a more controllable range. If successful validation occurs first in animals, it can significantly reduce mechanism uncertainty and provide the first batch of translational leads and development experience for human applications.

BT-202: Cell Therapy, Transforming Bad Cells into Brake Cells

This is the most aggressive mechanism among the three pipelines.

Traditional Treg cell therapy involves extracting Tregs from the patient, expanding them in vitro, and then reinfusing them. The problem is that Tregs are difficult to expand in large quantities, have poor stability, high costs, and their effects are not long-lasting.

Benerhera's BT-202 took a different path:By knocking down specific genes in conventional T cells (Tconv), attack-type T cells can be directly converted into Enforce-T cells with Treg functionality.These cells have a stronger binding affinity to DCs and can effectively suppress the ability of DCs to activate effector T cells, fundamentally interrupting the inflammatory circuit.

More importantly, the company claims to reduce manufacturing costs to 1/10 of similar products and strives for a breakthrough in achieving dosing once every 6 months to 1 year.

If this number is true, it will definitely be a disruption in the field of cell therapy.

What does the poster in Boston illustrate?

Back to today, CUE-401 at IMMUNOLOGY2026.

The idea is to inject a bifunctional protein that combines TGF-β and IL-2 mutein, delivering two signals simultaneously in vivo to synergistically induce FOXP3+ antigen-specific iTreg, which are converted on-site from conventional CD4+ T cells.

This is the underlying logic of BT-101,Point to the same end: enabling the body to produce more and stronger Tregs on its own, rather than uniformly suppressing the entire immune system from the outside.

The difference lies in the route of administration: CUE-401 is an injectable biologic with a more direct mechanism, potentially leading to faster onset; BT-101 is an orally administered small molecule with the natural advantage of compliance—patients do not need injections. Additionally, through the amplification effect of the gut microenvironment, it may have potential for expansion across multiple autoimmune indications.

These two paths are not mutually exclusive, but rather two different bets on the same track.

More importantly, this track was not officially endorsed by the Nobel Prize until 2025, but someone in China had already entered the field in 2021. Currently, BT-101 is the first of its kind globally to receive FDA IND approval.

Facing such a "cake," what does VC need to think clearly about?

First, this is not a story chasing the Nobel Prize hotspot.

Benerhera was founded in 2021, a time when Treg was truly an overlooked field. They didn’t enter because of the Nobel Prize; rather, they were rediscovered because of it. The core mechanism discovered by Professor Yan Shi stemmed from the efforts made in front of an atomic force microscope in 2007 — a long-term accumulation of fundamental research, not a result rushed by capital.

Second, the pipeline design reflects a platform-based mindset.

Three pipelines, covering oral small molecules (BT-101, IBD), topical small molecules (BT-201, skin inflammation), and cell therapy (BT-202, severe autoimmune diseases). Three technological forms, three different commercialization pathways, mutually validating and serving as safeguards for one another. Success in any one pipeline provides scientific endorsement for the other two. In SteadyState's view, it seems more like first validating BT-201 in animals, then using BT-101’s human safety data to build confidence, before advancing BT-202 along this subtle timeline.

Third, how big is the market?

There are approximately 300 to 500 million patients with autoimmune diseases globally, covering dozens of indications such as rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, psoriasis, and type 1 diabetes. The biggest pain point of existing treatment options is precisely the excessive immune suppression that leads to increased infection risks and long-term efficacy instability. The core value of Treg modulation, however, isPrecision Braking, Not Comprehensive Suppression。

If the Phase I data of BT-101 reads out safety signals in the second half of 2026 and enters Phase II in 2027, the valuation of this company will enter a new stage of leapfrog growth.

Scientists who start businesses often encounter two failure modes: one is that the founder-scientist needs to do everything themselves, turning the company into an expanded version of a lab; the other is compromising on the pipeline direction early on for financing purposes, shifting from mechanism-driven to market-driven.

Benerhera's current organizational structure appears to have avoided these two pitfalls: Professor Yan Shi focuses on overall direction and technical oversight, while Dr. Feng Liu (with experience in bringing 13 products to market and conducting over 80 clinical studies) leads company operations and product development. The division of responsibilities is clear, with each person fulfilling their role. Such a combination has given rise to several respectable companies in the history of China's innovative drug industry.

The Treg track has been developed for thirty years outside of China, but no significant generational gap has been established. Most of the fastest overseas projects have stalled at Phase IIa, due not only to the ongoing deepening understanding of Treg’s stability, persistence, and functional regulation within the human body, but also because manufacturing, quality control, homing, and clinical translation themselves are highly challenging.

Today, at the Boston Convention and Exhibition Center, data from CUE-401 is being discussed. Meanwhile, in China, BT-101 has entered human trials. History sometimes unfolds like this: when a field is challenging enough, entry is early enough, and the mechanisms are solid enough, what remains is to wait for the judge—clinical data—to deliver the final verdict.

This article comes from the WeChat Official Account"Molecular Homeostasis", Author: Sanlitun Information Flow Aunt Ning, 36Kr authorized release.