As innovative drug development advances into more challenging territories, antibody drugs have solidified their position as a core battleground in the global biopharmaceutical competition. However, the further the industry pushes the frontier, the more it must confront a stark reality: traditional antibody discovery is plagued by long cycles, high costs, and limited success rates, with highly homologous and difficult-to-drug targets posing persistent bottlenecks.

The key to securing a ticket for the next generation of antibody drugs lies in simultaneously enhancing efficiency, success rate, and predictability.

After years of dedicated platform development, ImmuNotion, a platform company focused on innovative antibody discovery, has delivered impressive results on both industrial and capital fronts.

On the industrial side, over the past three years, ImmuNotion has established collaborations with over 30 pharmaceutical companies, including several leading multinational corporations (MNCs), with its technology platform's value thoroughly validated by top-tier international partners. To date, the company has completed more than 200 early-stage antibody drug development projects spanning popular therapeutic areas such as oncology, autoimmune diseases, and CNS disorders.

On the capital side, ImmuNotion recently closed a Series A financing round of 250 million RMB, led by Vivo Capital with participation from Gaomai Yuanhang. Existing shareholders, including Xicheng Jinrui and Taiyu Investment, significantly increased their investments.

These achievements stem from ImmuNotion's core technology: the Massive-fragment Across Species *In situ* Replacement Technology (MASIRT®). This gene-editing technology, pioneered by a Chinese team, achieves three breakthroughs: it employs a linear artificial chromosome loading strategy to greatly enhance gene fragment capacity; enables single-operation, megabase-level DNA fragment replacement *in situ*, significantly reducing editing steps; and is species-agnostic, having already achieved large-fragment replacement across multiple species.

Leveraging this technology, ImmuNotion has built a suite of core platforms designed to improve the efficiency, success rate, and predictability of antibody drug R&D: a fully humanized mouse platform; the globally innovative ImmuAlpaca® alpaca mouse platform; and fully humanized rabbit and rabbit-derived single heavy-chain antibody rabbit platforms. It is reported that across the completed 200+ projects, these core platforms have demonstrated a stable immune response success rate significantly higher than traditional engineered mouse platforms. Even for complex targets with high homology and low immunogenicity, they reliably elicit potent immune responses and screen high-quality candidate antibodies—a rare feat in the industry that underscores the platform's stability and reliability.

Furthermore, supported by annual generation of massive, high-quality multi-species immune data, ImmuNotion has constructed an AI platform that can substantially improve antibody molecule screening efficiency and drugability. This AI platform, trained on vast, high-quality data, also unlocks new possibilities for global antibody drug development.

How did ImmuNotion build its original technology and platforms, both in China and globally? How did it create an innovation system driven by the dual engines of "fully humanized model animals + AI empowerment"? And why has it attracted numerous pharmaceutical companies, domestic and international, to collaborate? To explore these questions, we spoke with Dr. Zhang Jiwei, Founder and CEO of ImmuNotion.

The Industry Inflection Point: Precision as a Prerequisite for Next-Gen Antibody Drugs "Precision" is a term Dr. Zhang Jiwei emphasized repeatedly during the interview.

After years of rapid development, antibody drug R&D has transitioned from a focus on "availability" to a new phase demanding "accuracy, speed, and success." While novel molecules like bispecific/multispecific antibodies, bispecific ADCs, and nanobodies continue to emerge, traditional technical routes are showing limitations: humanization is time-consuming and risks losing high-quality molecules; difficult targets have low immune success rates; issues like bispecific chain mispairing and nanobody instability/aggregation directly increase R&D costs and failure risks. Simultaneously, clinical demands for high affinity, low immunogenicity, and high stability are rising.

"Through collaborations with multiple MNCs and leading domestic pharmaceutical companies, we clearly perceive a trend: only continuous precision development can meet the current demands of antibody drug R&D," Dr. Zhang stressed.

For MNCs and domestic innovative drug companies, precision is no longer optional but a core direction that must be breached—shorter cycles, higher success rates, and lower risks are essential to gain an edge in intense pipeline competition. This is precisely why ImmuNotion is favored by partners: with an innovative technology system from the ground up, ImmuNotion is turning "the impossible into the possible, and the possible into a high-frequency certainty."

The MASIRT® technology described earlier is the source of ImmuNotion's innovation and the foundation for meeting the pharmaceutical industry's need for "precision" in antibody drug R&D.

As a globally leading innovative technology capable of megabase-level precise *in situ* replacement, MASIRT® differs from traditional bacterial artificial chromosome (BAC) technology based on embryonic stem cells or CRISPR technology focused on gene therapy. It does not require multiple steps and waiting for embryonic stem cell culture, achieving precise *in situ* replacement of large fragments in a single operation. This translates to higher efficiency, higher success rates, and greater possibilities.

The drug development process is long and complex, with success hinging on two key stages: first, the ability to find drug-like, high-quality antibody molecules; second, the ability to accurately model disease and evaluate efficacy. Humanized mouse platforms, as a core technical pathway for fully human antibody development, have become a primary source of such molecules as fully human antibody drugs have gradually claimed a significant share of new antibody approvals.

Based on MASIRT® technology, ImmuNotion successfully built a fully humanized mouse platform in just 18 months—a process that typically takes 5-6 years in the market. By the end of 2023, ImmuNotion launched its first fully human antibody discovery mouse platform, ImmuMab®, effectively addressing common issues in traditional engineered mouse platforms like unstable immune responses, low serum titers, and insufficient antibody diversity. Experimental results show that in immunization projects with various antigen types, ImmuMab® mice consistently achieved potent immune responses, comparable to or even exceeding some wild-type strains, demonstrating advantages of high titer and high stability in fully human antibody discovery.

Building on the absolute advantage of ImmuMab®, ImmuNotion has further implemented its "precision" strategy over the following two years. To address different technical scenarios and target needs, it has successively launched new products in its fully human antibody platform series: ImmuMab®HK, ImmuMab®HKL, and ImmuMab®HL mice for conventional fully human antibody development; the fully human heavy-chain-only antibody discovery platform ImmuMab Heavy® mice and the globally innovative ImmuAlpaca® alpaca mouse platform for nanobody development; a rabbit-derived single heavy-chain antibody rabbit platform; the common light-chain antibody discovery platform ImmuMab Light® mice; and an upcoming fully human antibody rabbit platform for epitope bias and subtle difference target development.

Specifically, based on human immunoglobulin heavy chain (H), kappa light chain (K), and lambda light chain (L) genes, ImmuNotion systematically developed three fully human antibody models through differentiated gene combination strategies: ImmuMab®HK (H + K), ImmuMab®HL (H + L), and ImmuMab®HKL (H + K + L full coverage). This series, ranging from single light-chain combinations to dual light-chain full coverage, builds a hierarchical product matrix, providing the industry with antibody immune library sources of higher diversity and greater developability.

The fully human heavy-chain-only antibody discovery platform, ImmuMab Heavy® mice, perfectly inherits the advantages of human antibody diversity and high immune response capability from ImmuMab® mice. Compared to traditional monoclonal antibodies, it offers greater development freedom: it can directly develop therapeutics with unique properties, serve as targeted delivery tools for chemical drugs, or combine with other drug forms to create bifunctional or multifunctional biologic therapeutics. Beyond the fully human antibody discovery mouse platform, ImmuNotion's globally innovative ImmuAlpaca® alpaca mouse platform and fully humanized rabbit and rabbit-derived single heavy-chain antibody rabbit platforms have strategically positioned themselves, filling a market gap in multi-species, high-diversity model animals. Global patent coverage has been secured across major markets including mainland China, Europe, the US, and Japan.

The common light-chain antibody discovery platform, ImmuMab Light® mice, further enriches ImmuNotion's antibody discovery capabilities. The "common light-chain" technology effectively addresses heavy-light chain mispairing issues in antibody discovery by utilizing a universal light chain that can pair with various heavy chains to construct bispecific candidate molecules. Simultaneously, ImmuNotion has introduced other common light-chain mouse subtypes based on different light-chain V genes to meet the needs of different targets and candidate antibodies in various projects, further increasing the likelihood of successful bispecific construction.

"In the common light-chain domain, to meet the differentiated development needs of various targets, we have specifically built 10 dedicated adaptation platforms, achieving precise coverage of diverse target types. This multi-platform layout is a global first," Dr. Zhang added.

Through its differentiated platform portfolio, ImmuNotion achieves precise coverage for antibody drug R&D: for diagnostic antibodies and cell therapy products like CAR-NK and CAR-T, the fully humanized mouse platform provides efficient human antibody discovery support; for special targets requiring high affinity or low sensitivity, the fully humanized rabbit and rabbit-derived single heavy-chain antibody rabbit platforms offer unique advantages; in complex drug development like ADCs and bispecifics, the alpaca mouse platform and common light-chain platform better meet molecular design needs. Dr. Zhang stated that this "on-demand adaptation" platform matrix is a concentrated embodiment of ImmuNotion's "precision" R&D capability.

ImmuNotion's rapid entry into MNC supply chains and consistent securing of orders from renowned pharmaceutical companies worldwide validates Dr. Zhang's assertion that "antibody drug R&D has entered an era of precision."

Becoming a Chinese Partner for Global Antibody Innovation Goals determine strategy, and strategy influences development paths. In China and abroad, technology-focused Biotechs have evolved into different types of companies based on their objectives. The antibody discovery field is no exception.

ImmuNotion's positioning extends beyond being a technology service platform. From its inception, its core vision has been to leverage original Chinese technology to build internationally leading antibody discovery platforms, driving a leap in efficiency and success rates for global antibody drug R&D. It aims to become a Chinese partner for global antibody drug R&D innovation, bringing more breakthrough therapies to patients worldwide.

Around 2017, Dr. Zhang Jiwei was conducting postdoctoral research at the M.D. Anderson Cancer Center in the US, deeply studying antibody drug therapies for cancer. During this period, he not only saw the therapeutic potential of antibody drugs but also felt the gap in antibody drug R&D between China and the US.

At that time, China's innovative drug sector was just beginning to emerge, with novel antibody drugs still in their infancy. Many treatment needs of Chinese patients remained unmet. Seeking more potential treatment options, numerous cancer patients traveled great distances to the US each year.

The sight of Chinese patients struggling to seek new drugs abroad shocked Dr. Zhang, particularly the story of a farming couple who spent everything to treat their child's glioblastoma, which deeply moved him. "This farming couple didn't speak a word of English, but to treat their child, they resolutely sold everything and flew to the US."

This disparity and shock planted the seed of developing novel antibody drugs in Dr. Zhang's mind. However, he chose not to spend decades developing a single antibody drug. Instead, he opted to build a world-class platform based on original Chinese foundational technology, empowering pharmaceutical companies to develop more new drugs, better and faster, ultimately benefiting global patients.

"The improvement of innovative drug R&D efficiency and success rate doesn't rely on manpower accumulation but requires the support of innovative technology and correct strategy," Dr. Zhang analyzed.

Dr. Zhou Changyang shared a similar vision. Focused on gene editing tool development and gene editing therapy, Dr. Zhou was conducting research at the Institute of Neuroscience, Chinese Academy of Sciences. How to revolutionize global novel antibody development with foundational technology? After co-founding ImmuNotion in 2020, they answered this question with the birth of MASIRT® and the series of technology platforms.

"ImmuNotion's underlying logic is for the development of novel antibody drugs, which is completely different from a business-driven corporate strategy," Dr. Zhang emphasized. Centered on this positioning, ImmuNotion established three flexible collaboration models to better promote novel antibody drug R&D.

Today, these business models have received positive market feedback and achieved notable results. "For example, our Co-Development partner recently secured oversubscribed financing for a collaborative project, supported by multiple top-tier domestic funds and capital focused on biopharmaceutical investment."

In international collaboration expansion, ImmuNotion has also gained support from various parties, including MNCs. By the end of 2024, ImmuNotion successfully joined Bayer's Co.Lab co-creation platform, becoming the sole company within it providing a leading antibody discovery platform for global drug R&D partners.

AI Empowerment: Forging a New Paradigm for Antibody R&D At this critical juncture where global antibody drug R&D is evolving towards deeper source innovation, powerful AI tools, as a significant force, determine the efficiency and success rate of this transformation.

Leveraging the original Chinese MASIRT® technology, ImmuNotion has not only successfully built a new generation of fully humanized model animal platforms, gaining recognition from top domestic and international pharmaceutical companies including MNCs, but has also established the ImmuMabAI® antibody discovery platform, supported by rich data assets accumulated from diverse model animals and AI algorithms.

With the new generation of fully humanized model animal platforms and AI-powered R&D capabilities, ImmuNotion has created an innovation system driven by the dual engines of "fully humanized model animals + AI empowerment." While significantly improving screening efficiency and drugability, it is also attempting to provide a new paradigm for global antibody drug R&D.

The accuracy of an AI platform is inextricably linked to the quality and quantity of the data it learns from. Authentic, massive, and multi-dimensional native biological data determines the upper limit of intelligent R&D. Deeply understanding that "data is king," Dr. Zhang led the ImmuNotion team to successfully address the data challenges in novel antibody drug R&D.

The core challenge in antibody drug R&D begins with the biological foundation of B cells, the "antibody factories." B cells construct a primary antibody repertoire through V(D)J recombination, followed by affinity maturation driven by antigens, ultimately producing highly specific antibodies. Traditional genetically engineered mouse models often suffer from incomplete immunoglobulin gene replacement, leading to B cell developmental blockade, insufficient primary antibody repertoire diversity, and consequently low positive clone acquisition rates and poor screening efficiency post-antigen response.

Through its proprietary gene-editing technology, ImmuNotion achieved a key breakthrough in B cell immune repertoire construction: its B cell developmental pathway is highly consistent with wild-type strains, with normal V(D)J recombination efficiency, ensuring complete diversity of the primary antibody repertoire. Building on this, ImmuNotion monitors the entire lifecycle of B cells, from bone marrow development to peripheral differentiation and antigen response. Experimental data show that in an unimmunized state, the proportions of various B cell subsets in the platform are not significantly different from wild-type mice; after immune response, it effectively initiates germinal center reactions and affinity maturation, producing antigen-specific positive clones at orders of magnitude higher numbers.

"Because B cell development is unimpaired, its mechanisms for clearing self-reactive clones and promoting functional B cell survival are consistent with wild-type. This allows us to fully capture dynamic data of antibody generation—from initial B cell activation, somatic hypermutation, to terminal differentiation," Dr. Zhang explained. "Based on this, our B cell immune repertoire can rapidly provide thousands to tens of thousands of real sequences validated by *in vivo* natural selection, supplying high-quality biologically annotated data for AI model training, which is difficult for traditional engineered platforms to achieve."

Currently, ImmuNotion's platforms cover multiple species including human, mouse, alpaca, and rabbit, capable of annually generating massive, high-quality multi-species immune data, adaptable to diverse, multi-scenario antibody R&D needs. Differentiating itself from AI platforms reliant on single species or single technical routes, ImmuMabAI® advances towards the goal of being the "optimal AI antibody discovery platform" with core advantages of multi-species data synergy, full antibody type compatibility, and whole-process intelligent empowerment. Whether for bispecifics, ADCs, nanobodies, or multi-specifics against complex targets, ImmuMabAI® can provide efficient, precise source solutions, injecting "AI acceleration" into global antibody drug R&D.

From technology output to platform empowerment, from point collaborations to ecosystem co-creation, it is evident that ImmuNotion is integrating more pharmaceutical innovation resources, striving to provide a "Chinese solution" for global antibody drug R&D. Driven by original Chinese technology companies like ImmuNotion through "precision" layout, diversified collaboration, and AI empowerment, the global antibody industry has the potential to transition from "competition" to "collaboration," and from "efficiency improvement" to "paradigm innovation."