Meton Pharmaceuticals, Co-Founded by Academician Zhao Guoping, Files IPO Prospectus with Focus on First-in-Class Small Molecule Oncology Drugs

Small-molecule innovative drugs have witnessed rapid technological advancement in recent years, accompanied by a surge in startups, owing to their differentiated advantages, irreplaceable convenience, broad indications, strong market penetration, low cost, controllable quality, negligible immunogenicity, and minimal storage requirements.

Mitong Biois one such company, focusing on the development of novel small-molecule targeted anticancer drugs by targeting metabolic enzymes involved in tumorigenesis. Currently, Maitong Biopharma has four drug candidates in its pipeline, which are at various stages including IND-enabling studies, lead compound optimization, and molecular design, and it has secured multiple PCT patents.

How to Differentiate in the Crowded Small-Molecule Drug Arena? How to Achieve Source Innovation? These Are Questions That Maitong Biopharma Has Been Continuously Pondering. To This End, VCBeat Chengguo Bureau andDr. Zhang Shiyun, Co-founder of Maitong BiologyEngaged in an in-depth dialogue.

The founding team of Maitong Biology is a standard “Scientist + CEO” model, the lead scientist and founder is a renowned expert in cancer genomics and biomedical big data—Academician Zhao Guoping, the founding team members includeProfessor Xiong Yue, Professor Guan Kunliang, Professor Ding Sheng, General Manager Yang Jibin, and Dr. Zhang Shiyun.

In fact, as early as 2006, Professor Xiong Yue and Professor Kun-Liang Guan had already led the Fudan University team in researching the oncogenic effects of abnormally metabolizing enzymes in tumors. In 2011, they were the first globally to elucidate the mechanism by which IDH (isocitrate dehydrogenase) mutations cause cancer, with their specific research findings published inCellandSciencein the journal. Academician Zhao, who had previously provided coordination and assistance to two professors in their IDH R&D efforts, recognized the substantial unmet clinical need for IDH-targeted therapies and proposed a research direction focused on the development of innovative anti-tumor drugs targeting IDH.

Meanwhile, leveraging scientists’ extensive expertise in metabolic enzymes and tumor genomics, Maitong Bio has developed capabilities starting from tumor targets.“One-Stop” R&D System。

Following the discovery of new targets, identifying chemical molecules that can effectively inhibit these targets and conducting druggability assessments have become increasingly critical tasks. “The design and development of chemical molecules is the work of chemists; druggability assessment is the work of druggability experts,” revealed Zhang Shiyun. Academician Zhao and the two professors also invited the founding dean of the School of Pharmaceutical Sciences at Tsinghua University, who then held an endowed professorship at the University of California, San Francisco.Professor Sheng Dingand Senior Expert in New Drug R&DGeneral Manager Yang Jibin, to strengthen Maitong Biology’s capabilities in both chemical molecule design and the research and development of drug-like properties for compound molecules.

It is reported that Professor Ding Sheng has extensive experience in the design of small-molecule targeted drugs, while General Manager Yang Jibin boasts over 20 years of work experience in drug research and development (R&D) and production. He has also led the R&D and regulatory submission of 30 new chemical drugs and generic drugs, obtaining production approvals issued by the National Medical Products Administration (NMPA).

Certainly, in addition to the technical aspects, Academician Zhao has not overlooked the team's financing and business needs.

At that time, as an alumnus of Academician Zhao Guoping and Professor Xiong YueDr. Zhang ShiyunHe was also highly interested in the innovative drug development plans of these scientists. Holding a Ph.D. in Biology from an overseas institution and possessing extensive management and operational experience with companies both abroad and in China, he decided to join the Maitong team, where he would oversee investment, financing, and business operations for Maitong Biopharma.

Thus, Maitong Bio’s founding team, structured around a “scientist + CEO” model, has been fully assembled. The scientific founder’s background in biology positions Maitong Bio to pursue novel targets and develop first-in-class innovative drugs, while the CEO’s extensive industrial and commercial experience facilitates the translation of scientific discoveries into therapeutic products. Overall,The complementary and well-aligned backgrounds of the founding team at Maitong Bio enable effective integration across its innovative drug R&D platforms, ensuring smooth progress in research and development.“Dr. Zhang Shiyun stated.”

Guided by clinical value and centered on patient needs, developing first-in-class targeted anti-tumor drugs with genuine source innovation has always been the steadfast commitment of Maitong Biopharma. Underpinned by this original aspiration for source innovation, Maitong Biopharma has established four product pipelines, namelyIDH1, IDH2, ME3, and IRG1, and systematically conduct preclinical studies and advance toward clinical trials.

IDH1As the first target developed by Maitong Biology, IDH1 mutations occur at high frequencies in various tumors. Its indications include glioma, acute myeloid leukemia (AML), cholangiocarcinoma, melanoma, chondrosarcoma, and peripheral T-cell lymphoma, among other oncological diseases. Taking glioma as an example, its annual incidence rate reaches 5–8 per 100,000 population and is increasing at a rate of 1–2% per year. Current treatment primarily relies on chemotherapy and surgery, with a lack of targeted therapeutic agents, indicating a substantial market opportunity.

The second target isIDH2 Target“It shares functional similarities with IDH1, and its primary indication is also AML. ‘The gene sequences of IDH1 and IDH2 exhibit high homology, and they share identical metabolic catalytic functions; however, their subcellular localizations differ—one is located in the cytoplasm, while the other resides in the mitochondria,’ explained Zhang Shiyun.”

The third target isME3, This is because the co-deletion of the tumor suppressor gene SMAD4 and the Me2 gene renders cancerous tumor cells dependent on Me3 gene function, thereby enabling inhibition of Me3 through synthetic lethality; its indication is pancreatic ductal adenocarcinoma, which accounts for 90% of pancreatic cancers.

Article 4 PipelineIRG1It is a novel target for cancer immunotherapy and is applicable to a variety of tumors, including breast cancer, colorectal cancer, head and neck squamous cell carcinoma, lung cancer, liver cancer, prostate adenocarcinoma, and endometrial cancer. Therefore, inhibition of this target can achieve broad-spectrum antitumor effects. In animal models, knockout of the IRG1 target in combination with PD-1 antibodies increased the antitumor efficacy of PD-1 antibodies by nearly fourfold, indicating that small-molecule inhibitors targeting IRG1 hold great promise for highly effective antitumor therapy.

Zhang Shiyun told VCBeat that Mitong Biopharma has signed a cooperation agreement with the Institute of Biomedical Sciences at Fudan University for the development of IRG1 inhibitors, based on drugability requirements and guidelines. In addition, Mitong Biopharma has several other inhibitor development programs targeting different pathways currently underway.

Among the four core pipelines mentioned above,The IDH1/2 targets and IRG1 were independently developed by the team’s founding scientists.ME3 was identified by the team through analysis and screening of The Cancer Genome Atlas (TCGA) and big data.

How does Maitong Biologics independently develop innovative drugs? In fact, Maitong Biologics has established a comprehensive R&D framework for targeted anti-tumor innovative drugs in China and built four platforms, includingBiological Discovery Platform, Computer-Aided Drug Design (CADD) Platform, Druggability Evaluation and Pharmacology & Toxicology Platform, and Pharmaceutical Research Platform。

First, throughBiological Discovery Platform: Independently Developed Novel Expression System and Completed Molecular, Biochemical, and Cellular Screening, Zhang Shiyun revealed that during the development phase of the ME3 target, the team needed to obtain the ME3 protein for subsequent research and testing. However, due to the uniqueness of the target, expression of the ME3 protein was not straightforward, and it was not commercially available. Consequently, the team had to independently express, extract, isolate, and purify the ME3 protein. At this stage, the team leveraged its biological discovery platform to adjust and optimize the expression system and integrate resources, ultimately succeeding in obtaining the target protein.

Secondly,Utilize an AI-assisted drug design platform to complete drug molecule design and subsequent testing., the team's medicinal chemists leveraged an AI-driven computer-aided drug design platform to conduct precise molecular design, guided by structure-activity relationship (SAR) principles of small-molecule inhibitors against the target and druggability requirements, thereby significantly reducing the number of hit compounds and effectively minimizing workload.

Specifically, the team designs dozens of hit compounds in each round, followed by activity assays and data analysis for the targeted enzymes. This approach facilitates the structural optimization, modification, and further screening of subsequent hit and lead compounds, thereby saving significant time and costs.

Next isConduct a variety of in vivo and in vitro experiments through druggability evaluation and pharmacology and toxicology platforms.to evaluate the safety and efficacy of screened compounds, and collaborate with leading domestic CROs to conduct pharmacokinetic (PK), pharmacodynamic, and toxicological assessments of candidate compounds. The pharmaceutical development platform focuses on process development and quality research for clinical candidate compounds, determining dosage forms and crystal forms in accordance with principles of patented route industrialization, and producing active pharmaceutical ingredients (APIs) required for clinical trials, thereby advancing preclinical development of small-molecule compounds.

The increased investment from the four major platforms has enabled Maitong Biopharma to integrate the upstream and downstream loops of drug development. This signifies that Maitong Biopharma can independently manage the entire process, ranging from the discovery of oncogenic mechanisms and target validation, through the autonomous design of small-molecule inhibitors, to efficacy studies, pharmaceutical development, pharmacokinetics, and toxicology, culminating in IND filing and registration.

On December 1, 2022, the FDA approved olutasidenib (Rezlidhia) capsules, an IDH1 (isocitrate dehydrogenase 1) inhibitor, for the treatment of adult patients with IDH1-mutated acute myeloid leukemia (AML). This brings the total number of FDA-approved IDH1 inhibitors globally to two, the other being ivosidenib (AG-120), which was approved in 2018.

In fact, the approval of Olutasidenib presents both a challenge and an opportunity for Maitong Biopharma.

This meansIDH1 Target and the Efficacy of Its Inhibitors, Zhang Shiyun told Chengguo Ju that among the IDH1 pipeline, Ivosidenib (AG-120) was the first to be launched, and the approval of Olutasidenib for AML further validates the efficacy of IDH1-targeted small-molecule inhibitors in anti-tumor therapy.

Although the IDH target has been identified for only about a decade, and it has been roughly ten years since the scientific founders of Mitong first elucidated its oncogenic mechanism and proposed 2-hydroxyglutarate (2HG) as a tumor metabolite and biomarker derived from mutant IDH, IDH has now become one of the major oncology targets. The successive market launches of two drugs have significantly enhanced the visibility and recognition of IDH1-targeted innovative therapies within the medical community and the market, thereby helping to expand the market size and capacity for IDH1-targeted drugs.

Where do the challenges lie? What are the advantages of Maitong Bio’s products?

Benchmarking against the targeted drug Ag120, Zhang Shiyun introduced that comparative trials conducted by the team using small molecules with the same molecular structure as Ag120 revealed that Maitong Bio’s IDH1 mutant inhibitor—MT001 demonstrates differential advantages in cardiac safety and blood-brain barrier penetration.

In terms of cardiac safety, it is generally considered that a drug exhibits favorable cardiac safety when its IC50 for the hERG potassium channel is equivalent to or higher than 10 μM. The relevant data for Maitong Bio’s IDH1 mutant inhibitor exceeds 30 μM, well above the acceptable threshold, whereas the benchmark compound AG-120 is close to and slightly below 10 μM. Additionally, regarding blood-brain barrier penetration, MT001 has an average blood-brain permeability rate of nearly 40%, resulting in brain drug exposure levels 20 times higher than those of AG-120; therefore, it can be used for the treatment of glioma.

Moreover, successful projects also require robust management. Maitong Biopharma places significant emphasis on drug development timelines and, through resource integration, aims to accelerate the pace and enhance the quality of its preclinical research. Currently,The Pre-IND application for the IDH1 pipeline has been approved, advancing to the IND stage, with Phase I clinical trials expected to commence in early 2023., In addition, the IDH2 target has entered the lead compound optimization stage, while ME3 and IRG1 are in the preclinical research stage.

In addition to prioritizing efficiency, Maitong Biology has also demonstrated precise acumen in financing and capital management. Amid the current “capital winter,” when fundraising is particularly challenging for innovative enterprises, making prudent use of every “bullet” is not only a demonstration of responsibility toward investors and a foundation for earning their trust, but also an opportunity to test the team’s creativity and managerial capabilities. Zhang Shiyun stated, “We have completed our Series A financing and currently have a team of more than 20 members, over 60% of whom hold master’s or doctoral degrees. We are now launching our Series A+ round, with the funds from this round primarily intended forTo be used for the Phase I clinical trials of IDH1 and preclinical development of other pipeline candidates, with a portion allocated to team expansion., recruiting more scientists to accelerate the R&D process, and our team has also established in-depth collaborations with the Eastern Hepatobiliary Surgery Hospital and leading domestic CROs. We are confident in the advancement of the project and the company’s development.”