Beijing NeoMatrix Biosciences Files IPO Prospectus: Pioneering Neoantigen-Based Cancer Immunotherapy Powered by Big Data and AI

Neoantigen-based tumor immunotherapy is the treatment modality with the greatest potential to conquer cancer, hailed as the ultimate solution among various tumor immunotherapies. As is well known, all tumors arise from mutations in normal host cells; however, the tumor mutation spectrum varies from patient to patient. Consequently, since 2015, multiple countries, including China and the United States, have launched precision medicine initiatives, aiming to overcome cancer through personalized therapeutic regimens. To date, however, the vast majority of cancer treatment approaches fail to achieve truly precise therapy.

The theoretical foundation of neoantigens is well-established. First, tumor cells all carry DNA mutations. Second, according to the central dogma, the most fundamental principle of molecular biology, DNA mutations lead to protein alterations. The primary function of the human immune system is to monitor for mutated proteins and eliminate cells harboring them, namely tumor cells. For various reasons, tumor cells “cleverly” evade immune surveillance, thereby enabling their initiation and progression into malignant disease.

Immune checkpoint inhibitor therapies (anti-PD-1/PD-L1 and anti-CTLA), which were awarded the 2018 Nobel Prize, have demonstrated significant clinical efficacy, confirming the potential of immune cells (primarily cytotoxic T cells) to efficiently kill tumor cells. However, since most patients lack tumor-specific cytotoxic T cells, immune checkpoint inhibitor therapies (such as Keytruda or Opdivo) are effective only in a small subset of patients.

Neoantigen therapies offer new hope for cancer patients by precisely stimulating the patient’s immune system to spontaneously generate a substantial number of tumor-specific cytotoxic T cells. Although neoantigens have not yet been approved for clinical use by regulatory authorities as a novel therapeutic agent, numerous top-tier global medical research centers and pharmaceutical companies have demonstrated their clinical safety and highly promising efficacy through extensive clinical trials.

Practice has demonstrated that neoantigens represent the first class of oncology therapeutics in history that are fundamentally dependent on big data and artificial intelligence algorithms. On one hand, the human genome consists of 3 billion base pairs, and tumor patients harbor hundreds to tens of thousands of mutations. Accurately identifying patient-specific mutations from these 3 billion DNA bases, and subsequently using AI algorithms to calculate mutation targets capable of triggering immune cell attacks, relies heavily on omics big data analytics and AI-based precise target identification technologies. On the other hand, there are no fewer than 10⁹ Different types of immune cytotoxic cells (cytotoxic T cells) require the support of massive tumor immunology big data and the latest tumor immunology data analysis algorithms to accurately screen out, from billions of T cells, those capable of specifically killing tumors. Therefore, although the concept of using neoantigens for tumor treatment was proposed as early as twenty years ago, it lacked the support of corresponding screening and identification technologies. It is only with the current development of omics big data and artificial intelligence algorithms that this concept has become feasible.

Beijing NeoAntigen Biotechnology Co., Ltd. (hereinafter referred to as “NeoAntigen Bio”) was established in November 2017. Its founding team brings together world-leading experts in bioinformatics, artificial intelligence, big data, and tumor immunology. Leveraging years of technological accumulation and reserves, the company has innovatively developed a comprehensive pipeline spanning from neoantigen design (NeoOne™) to neoantigen-specific T cell screening (Neo-T™). Based on extensive animal studies validating the safety and efficacy of NeoOne™-designed neoantigens, NeoAntigen Bio has jointly initiated clinical trials for neoantigen-based tumor immunotherapy with multiple Grade A tertiary cancer hospitals in China.

Neoantigen-based therapy is a novel therapeutic approach that integrates multi-omics big data, tumor immunology, bioinformatics, and artificial intelligence. The drug development pipeline is lengthy and involves numerous stages, thereby demanding exceptionally comprehensive capabilities from the development team. Dr. Zhou Yiming, founder of Beijing NeoAntigen Biotechnology Co., Ltd., along with his technical team, possesses extensive interdisciplinary R&D experience and industry expertise. Their in-depth understanding and mastery of oncology, immunology, and biological big data technologies make them the team best positioned and most capable of addressing these challenges.

Dr. Zhou Yiming, Founder of New Antigen Biotech

Dr. Zhou Yiming has engaged in research and development for many years across multiple fields, including bioinformatics, genomics, oncology, and immunology. During his doctoral studies, he specialized in bioinformatics under the supervision of Professor Cheng Jing, a senior academician of the Chinese Academy of Engineering. After going abroad in 2005, he worked and studied at Harvard Medical School and other renowned medical centers for ten years. In 2014, he returned to China to serve as the Dean of the Institute of Translational Bioinformatics and Chief Biomedical Information Officer at CapitalBio Corporation. From 2015 to 2017, he served as the Chief Scientist and successfully led the completion of China’s first “863” Program project on biomedical big data.

During his time in the United States, Dr. Zhou Yiming worked at a world-leading center for research and treatment of multiple myeloma (an immune system cancer), where he conducted in-depth studies on the interplay between immunity and tumors. Dr. Zhou openly acknowledges that this experience played a decisive role in founding NeoAntigen Biologics. Leveraging his dual background in academia and industry, Dr. Zhou—who integrates expertise in big data, immunology, oncology, and bioinformatics—decided to launch his venture to accelerate the development of neoantigen technologies and strive for early regulatory approval of his drug candidates.

Driven by a sacred mission and shared goal to conquer cancer, as well as by their recognition of the promising prospects of neoantigen technology and the NeoAntigen Bio team, numerous heavyweight figures from academia and the pharmaceutical industry have joined Beijing NeoAntigen Bio as partners or advisors. These include top professors from Harvard University and Tsinghua University School of Medicine, as well as leading experts in the field of biopharmaceutical research and development.

Two Nature articles published in 2017 reported the Phase I clinical trial results of neoantigen studies from the United States and Germany, sparking a surge in the development of neoantigen-based immunotherapies. In just over two years, neoantigen cancer immunotherapy has become a primary focus and R&D hotspot for the scientific community, pharmaceutical industry, investment institutions, and emerging biotech companies. While neoantigen clinical trials are rapidly expanding worldwide, the greatest challenges in neoantigen drug development have gradually come into clear view.

The upstream segment of the neoantigen technology chain involves genomic sequencing to acquire multi-omics big data; the midstream focuses on neoantigen prediction, analyzing multi-omics big data to screen for optimal neoantigens; and the downstream encompasses neoantigen synthesis and drug delivery—via direct subcutaneous injection or loading onto dendritic cells (DCs), among other methods. Technologies such as genomic sequencing, peptide synthesis, and DC loading are already highly mature and have been applied clinically for many years, thus they do not constitute bottlenecks in neoantigen technology.

The greatest challenge in the development of neoantigen technology lies in the intermediate, yet core, segment of the pipeline:Neoantigen Prediction. As previously mentioned, accurate neoantigen prediction requires massive amounts of data and computational power:

Multiple algorithms for neoantigen prediction have been published in the academic community; however, most of these algorithms focus only on one or a few steps within the overall neoantigen prediction process, failing to establish a complete workflow. Leveraging its profound expertise in bioinformatics and AI technology, NeoAntigen Biotech has successfully developed NeoOne™, the world’s most comprehensive neoantigen design platform. NeoOne™ has achieved breakthroughs in core algorithms for critical stages, including tumor gene mutation identification, HLA affinity calculation, and neoantigen peptide optimization, thereby securing NeoAntigen Biotech’s leading position in international neoantigen design competition. Notably, all core algorithms of NeoOne™ are independently developed and have secured more than 10 software copyrights and related patents, thereby mitigating potential risks of international intellectual property disputes.

Animal experimentation is a critical component of all drug development processes and is particularly vital for the practical application of neoantigens. “I find it quite puzzling that most companies engaged in neoantigen R&D, including top-tier international innovative pharmaceutical firms, have not placed sufficient emphasis on animal studies,” remarked Dr. Zhou Yiming. NeoAntigen Therapeutics places great importance on animal experiments, not only because they provide evidence of drug safety and efficacy, but also because they serve as the optimal platform for validating neoantigen prediction algorithms. Currently, the industry predominantly relies on the ELISpot technique to validate neoantigen design outcomes.

“However, we recognized early on that ELISpot can only validate one aspect of neoantigen prediction: whether the peptide can be presented by HLA. Critical issues such as whether the peptide accurately covers the mutation site, whether the peptide sequence is correct, whether it is expressed in tumor cells, and whether it can elicit an effective T-cell attack cannot be verified through ELISpot. Even for validating peptide presentation alone, ELISpot has inherent limitations that result in low sensitivity.” Therefore, NeoAntigen Biotech has consistently relied on animal experiments as the most important platform for verifying the safety and efficacy of neoantigens, as well as for validating and iterating its neoantigen design algorithms. To date, NeoAntigen Biotech has completed more than 30 batches (over 1,000 mice) of mouse experiments, thoroughly demonstrating the safety and efficacy of neoantigens and contributing multiple times to the improvement and upgrading of the NeoOne™ neoantigen design platform.

Leveraging the mature NeoOne™ platform, NeoAntigen Therapeutics has initiated clinical trials targeting various solid tumors after obtaining safety and efficacy data from animal studies, in collaboration with multiple Grade A tertiary hospitals across China. Among these, the clinical study titled “Clinical Study of Individualized Neoantigen Tumor Peptide Therapy for Genomically Unstable Solid Tumors,” conducted at Chongqing University Cancer Hospital, is currently recruiting patients, with indications including ovarian cancer, breast cancer, and gastrointestinal cancers. In partnership with Xuanwu Hospital of Capital Medical University, NeoAntigen Therapeutics has received funding from the Beijing Municipal Science & Technology Commission’s Major New Drug Development Special Project and is poised to launch clinical trials for patients with advanced glioma.

Benefiting from years of R&D accumulation in multiple fields, including tumor immunology, genomics, and bioinformatics, Dr. Zhou Yiming possesses interdisciplinary insights that integrate diverse domains. It is this insightful perspective that guided NeoAntigen Biologics to prioritize neoantigen drug development as its initial strategic focus during its inception, thereby establishing its core competitiveness.

“All roads lead to Rome,” and NeoAntigen Bio has chosen neoantigens. “The theoretical foundation for neoantigens is robust; in theory, they can be applied across all cancer types, representing the only current approach with the potential to conquer tumors. That is why we have chosen this path.” Coincidentally, Genentech, a top global pharmaceutical company, explicitly stated earlier this year: “After evaluating 3,300 different tumor immunotherapy drugs in clinical or preclinical stages, we selected neoantigens.” Indeed, great minds think alike.

“The essence of tumor immunity is simple: it is a battle of offense and defense between cytotoxic T cells and tumor cells,” introduced Dr. Zhou Yiming. “In the human body, T cells specifically recognize neoantigens on tumor cells through T-cell receptors (TCRs), thereby precisely eliminating them. Therefore, identifying targets for T cells is the cornerstone of all tumor immunotherapies. Without accurate prediction of neoantigens, peptide vaccines, mRNA vaccines, dendritic cell (DC) vaccines, and T-cell therapies would lack targeting specificity, making clinical efficacy unattainable. This has been the primary reason for the slow clinical progress in cellular cancer therapies over the past decade.”

Even with a clear understanding and acceptance of the concept that neoantigens are the cornerstone of all tumor immunotherapies, the formidable challenges inherent in neoantigen design have deterred the vast majority of companies. “We have confronted these difficulties head-on. Over the past two years, our team has overcome one obstacle after another in the process of neoantigen design and drug development, forging ahead despite every hardship. The journey has been both arduous and exhilarating. In particular, as our team members observed increasingly promising efficacy of our designed neoantigens in animal studies, they became firmly convinced that our efforts will help humanity gradually conquer cancer within the next decade.”

Recent studies have reported that mass spectrometry can be used to directly detect neoantigens presented by HLA on tumor cells. Does this mean that algorithms are no longer important? “The technology for detecting HLA-presented peptides via mass spectrometry is still under continuous development and has not yet matured enough for direct application in the clinical practice of neoantigen analysis. Professor Wu’s team at Harvard Medical School reported the use of mass spectrometry for neoantigen detection in the journal Immunity in 2014; however, the clinical trial initiated by her team in 2018 still employed algorithms to predict HLA–neoantigen affinity.”

A 2018 article published in Nature Biotechnology reported that they detected neoantigens via mass spectrometry and then refined their algorithms using the resulting data. The primary objective remained algorithmic improvement. “Why not directly apply the mass spectrometry results?” Dr. Zhou Yiming explained, “The main reason mass spectrometry has not yet been adopted in clinical practice is that this assay requires large tumor tissue specimens (greater than 1 cm³), suffers from low technical sensitivity, and yields a high rate of false-negative results.”

So, after the neoantigen design is completed, there are still many delivery routes to choose from. Why did NeoAntigen Bio choose direct subcutaneous injection of peptides? “Because it is the simplest, safest, and most effective approach.” Leveraging years of R&D experience in the field of tumor immunology, Dr. Zhou Yiming made this choice at the very beginning of the development process. “We do not rule out other technical approaches; we simply believe that peptides are the most suitable option at present. mRNA is a very powerful drug platform, but similar to the mRNA drugs in Moderna’s pipeline, each new mRNA sequence requires prolonged optimization to ensure stable and efficient protein expression in cells. However, due to the highly personalized nature of neoantigens, it is impossible to optimize each mRNA sequence for every patient, making the clinical implementation of this technology extremely challenging.

A drawback of neoantigen-loaded dendritic cell (DC) vaccines is that DCs generated in vitro from monocytes exhibit significantly lower efficiency in peptide presentation and T-cell stimulation compared to naturally occurring DCs in vivo. This may explain the particularly limited number of international clinical trials involving neoantigen-loaded DCs. T-cell therapy is likely the most promising direction among these approaches, as it not only enables the generation of tumor-specific T cells through neoantigen stimulation but also allows for genetic modification of T cells using genome-editing technologies. Such modifications can enhance the in vivo expansion of tumor-specific T cells, promote efficient infiltration into tumor tissues, and help overcome immune suppression. Nevertheless, T-cell therapy still faces numerous challenges. Dr. Zhou Yiming added, “These represent our current perspectives; we do not exclude any technology. NeoAntigen Bio has already partnered with leading domestic cell therapy companies to develop novel neoantigen-stimulated T-cell therapies. In the future, we hope to engage in deeper collaborations with more research institutions and pharmaceutical enterprises, both in China and abroad, that are dedicated to neoantigen-based treatments, so as to accelerate the clinical development of neoantigen drugs and benefit patients at an earlier stage.”

When it comes to cell therapy, it is well known that CAR-T technology has achieved remarkable success in the treatment of B-cell leukemia. Efforts have also been made to apply CAR-T technology to solid tumors. So, what are the advantages and disadvantages of neoantigen-based or neoantigen-stimulated T-cell therapy compared with CAR-T? “The most significant advantage of neoantigen-stimulated T-cell therapy lies in target selection. CAR-T therapy requires cell targets to be membrane proteins specifically expressed on tumor cells. Using big data technologies, we screened expression profiles of more than 20,000 genes across over 10,000 cancer patients but failed to identify targets as excellent as CD19, CD20, or BCMA. This may represent the primary challenge for the future application of CAR-T in solid tumors. In contrast, the targets of neoantigen-stimulated T cells arise from mutations in tumor cells, naturally possessing tumor-cell specificity. Furthermore, tumor-specific T-cell populations can be generated by stimulating T cells with multiple neoantigens targeting different mutation sites, enabling synergistic attack and elimination of tumor cells.”

Through advances both domestically and internationally, along with preclinical and clinical data from NeoAntigen Biologics, we have seen the dawn of neoantigen-based therapies overcoming tumors. However, there is still a considerable distance to go before achieving complete tumor control. For instance, how should we treat tumor patients with low expression of HLA (antigen-presenting proteins)? How should we manage patients with complex tumor immune microenvironments? And how should we treat patients with advanced-stage tumors who have compromised immune function?

In response to these challenges, NeoAntigen Biotech has developed its own strategic solutions and layout. With single-cell technology paving the way, the company is pursuing a multi-pronged approach involving neoantigens, TCR-T cell therapy, and combination drug regimens. Since its inception, NeoAntigen Biotech has leveraged big data from single-cell omics to study the tumor microenvironment. To date, it has completed single-cell omics data analysis for hundreds of tumor samples across various cancer types, pioneering the virtual reconstruction of immune microenvironments for different tumors at the single-cell level. This achievement provides a robust technical platform for biomarker screening and the design of combination therapy protocols. Furthermore, NeoAntigen Biotech has established a cell laboratory fully compliant with Good Manufacturing Practice (GMP) standards. In collaboration with industry partners and powered by its proprietary NeoTCR™ platform, the company is developing next-generation Neo-T™ T-cell therapies and NK cell therapies.

“There will definitely be no problem; we can conquer cancer,” said Dr. Zhou Yiming with full confidence.