The $7.8B Bet on mRNA-TCE: Who Will Capture the Next Wave of Innovation?

By: Zhu Ping, Li Jiaying

The mRNA sector is seeing new variables emerge.

On October 2, Abogen officially announced a collaboration with Novartis. Novartis has secured the exclusive global license to Abogen's core asset, ABO2203, along with an option to develop additional new projects based on Abogen's RNA platform. Under this deal, Abogen will receive an upfront payment of $575 million, with potential milestone payments totaling up to approximately $7.2 billion if all options are exercised.

Ying Bo, CEO of Abogen Biosciences, stated that this collaboration demonstrates that Abogen's RNA platform is not limited to preventive vaccines and holds significant potential for expansion. The narrative around mRNA technology is evolving from vaccines into the therapeutic realm, with the core shift enabling human cells to directly produce therapeutic proteins, thereby activating the immune system through T-cell engagers (TCEs). Notably, Novartis has secured more than just a single candidate drug; the agreement also includes options for the development of future projects on the RNA platform.

Fiona Marshall, President of the Novartis Institutes for BioMedical Research, stated that mRNA-encoded T-cell engagers represent a novel approach capable of generating these molecules in vivo, thereby complementing existing therapies. Novartis aims to further unlock the potential of ABO2203 and expand the application scenarios of Abogen’s RNA platform. The focus of multinational pharmaceutical companies has shifted from whether a single mRNA drug can succeed to whether mRNA can serve as a next-generation drug development platform.

The question then arises: as mRNA technology expands into more complex therapeutic areas such as T-cell engagers (TCEs) and autoimmune diseases, what ultimately determines a company's ceiling—is it the molecule itself or the delivery technology?

Notably, a significant shift has also emerged in the capital markets. On October 2, while the Hang Seng Index closed 2.6% lower, METiS TechBio-P (07666.HK) closed at HK$18.52, representing a 3.75% gain. While single-day stock price movements cannot be simply attributed to the transaction between Novartis and Abogen, market attention toward the foundational capability of “delivery” is rising against the backdrop of sustained industry interest in mRNA-TCE and in vivo immune engineering.

This is also why METiS TechBio warrants a fresh look. Rather than simply following the mRNA-TCE hype, METiS is targeting more fundamental challenges in this field: how to precisely deliver mRNA to target tissues and cells, and ensure the successful expression of therapeutic proteins within the human body. The significant transaction between Novartis and Abogen is opening a new window of observation for this still-early-stage sector.

What Novartis values is not just the ABO2203 molecule, but also the new potential that mRNA technology combined with TCEs may unlock in the field of autoimmune diseases.

TCE is not a new concept. The logic of traditional TCE therapeutics involves binding to T cells at one end and target cells at the other, bringing the two cell types into close proximity to facilitate T cell-mediated clearance of the target cells. In the field of oncology, this mechanism can be employed to kill cancer cells. If applied to autoimmune diseases, it offers the opportunity to precisely eliminate aberrant B cells, thereby correcting dysregulated immune responses at their source.

This is also why B-cell depletion strategies have regained attention in recent years. Traditional immunosuppressive drugs often require long-term, continuous administration, whereas deep B-cell depletion holds the promise of inducing more prolonged disease remission. CAR-T therapy has already validated the potential of this approach in certain autoimmune diseases; however, the complex manufacturing and infusion processes associated with cell therapies impose higher demands on medical resources and safety management. In contrast, enabling patients' own cells to transiently produce T-cell engagers (TCEs) in vivo may offer a path toward greater standardization.

The innovation of ABO2203 lies precisely here. Instead of directly administering TCE proteins into the human body, it leverages an mRNA-LNP system to enable transient expression of CD19×CD3 TCE in human cells. Theoretically, this approach can alter the pharmacokinetic profile of traditional protein-based TCEs, eliminating the need for repeated infusions of exogenous proteins by utilizing mRNA to sustain endogenous TCE production over a period of time. This represents a promising avenue worth validating for addressing longstanding challenges in the TCE field, such as peak drug exposure and cytokine release syndrome. However, as the project remains in the early stages of clinical exploration, no definitive conclusions can yet be drawn regarding its safety advantages.

Data previously disclosed for ABO2203 has begun to attract industry attention. At the 2026 AACR Annual Meeting, Abogen presented the first-in-human data for this drug in relapsed/refractory B-cell non-Hodgkin lymphoma. The objective response rate (ORR) reached 100% in the nine patients enrolled in the highest dose cohort, with no observed cytokine release syndrome (CRS), dose-limiting toxicities, or neurological adverse events. However, the sample size remains small; these results should be regarded primarily as a signal of technical feasibility rather than a definitive conclusion on clinical efficacy.

On September 18, Abogen, in collaboration with the team from Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, published a study online in Cell, further advancing mRNA-encoded TCEs into the field of autoimmune diseases. In three patients with refractory immune thrombocytopenia (ITP), rapid clearance of B cells in peripheral blood and bone marrow was observed, with platelet counts recovering and maintained for six months; adverse events were predominantly grade 1–2. Although the sample size remains limited, these preliminary findings suggest that mRNA-encoded TCEs are not solely applicable to oncology, as the approach of "B-cell depletion and immune remodeling" has shown early signals of clinical feasibility.

Therefore, Novartis' deal should not be simply interpreted as "spending $7.2 billion to acquire one mRNA drug." ABO2203 is the most mature asset in the portfolio, while the options included in the transaction secure future opportunities from Abogen's RNA pipeline. The deal essentially comprises two layers: the first involves acquiring an mRNA-TCE that has already entered clinical validation, and the second secures the potential of subsequent RNA pipeline candidates through options.

This signal is even more evident when viewed in the context of Novartis's sustained efforts over the past year to seek out external innovative assets. When the internal pipelines of multinational pharmaceutical companies face pressure, the purpose of external business development (BD) is no longer merely to fill a specific product gap, but rather to identify technological platforms capable of continuously generating next-generation therapeutics. Consequently, Abogen's value is no longer tied solely to the ultimate success or failure of ABO2203, but is instead linked to the future sustained output capability of its entire RNA platform.

As the research focus shifts further from "what mRNA encodes" to "where mRNA is delivered," the long-underestimated core bottleneck in industrialization—delivery—has begun to come to the fore.

For mRNA-TCEs, the TCE determines the therapeutic target, while delivery systems such as LNPs determine whether the drug can truly reach the target cells and tissues, and whether this delivery capability can be extended to other mRNA therapeutics. Novartis' deal did not assign a separate valuation to the delivery platform; however, the inclusion of options for future projects on the RNA platform underscores the importance of foundational technological capabilities.

From AbbVie's previous acquisition of Capstan Therapeutics to the current collaboration between Novartis and Abogen, large pharmaceutical companies are continuously seeking new technologies capable of modulating immune cells in vivo. Capstan chose to enter the field through autoimmune diseases; AbbVie acquired Capstan in 2025 for up to $2.1 billion, with core assets including targeted LNPs capable of generating CD19 CAR-T cells in vivo and the tLNP RNA delivery platform. Novartis, meanwhile, has set its sights on mRNA-encoded TCEs.

The two technical approaches differ: one involves the direct in vivo generation of CAR-T cells, while the other enables human cells to produce TCEs. However, the underlying logic is highly consistent—can complex immune engineering procedures, previously performed ex vivo, be directly conducted within the patient's body?

If this direction is ultimately validated by clinical data, the positioning of mRNA may shift. Historically, the most well-known application of mRNA has been in vaccines; however, the industry is now attempting to transform mRNA into a more versatile "in vivo drug manufacturing platform," ranging from in vivo CAR-T to mRNA-based T-cell engagers (mRNA-TCE). Instead of directly infusing finished therapeutic proteins or cells, this approach delivers instructional sequences that enable the body's own cells to synthesize therapeutic molecules.

This is precisely why the Novartis deal must be understood within a broader industrial context. Abogen has secured not only the upfront payment and milestone payments for ABO2203, but Novartis has also obtained exclusive options on other projects within Abogen's RNA platform. The subject of the transaction has, in effect, extended beyond a single TCE molecule to encompass the ongoing capability to develop novel RNA therapeutics.

But new questions have emerged: If mRNA truly becomes a programmable drug platform, what will be the key determinant of its success or failure?

The answer increasingly points to delivery.

Professor Hamideh Parhiz, Co-Founder of Capstan Therapeutics, and Dr. Caida Lai, Co-Founder and CEO of METiS TechBio, both highlighted in their dialogue at the CSGCT conference that the ultimate translational success of platform technologies hinges critically on efficiency, with delivery being a key component.

mRNA itself offers substantial design flexibility, but the true challenge lies in precisely delivering it to target cells and tissues and achieving sufficient expression at the appropriate time. As applications expand from vaccines to the modulation of immune cells, delivery requirements become significantly more stringent. While lipid nanoparticles (LNPs) have sufficed for certain scenarios in the past, targeting B cells and T cells, with lymph nodes and the spleen as target organs, necessitates further solutions for cell- and tissue-specific targeting. For mRNA-based T-cell engagers (mRNA-TCEs), delivery efficacy may even directly determine whether the intended immunomodulatory effects are achieved.

Therefore, the next round of mRNA competition will not merely be about who designs superior mRNA sequences; delivery systems are likely to become the new primary battleground. If a delivery technology can only support a single drug, it is more akin to a tool for developing a specific product. However, if it can accommodate the continuous swapping of mRNA, T-cell engagers (TCEs), and other immunomodulatory molecules while maintaining stable delivery and expression capabilities, it has the potential to evolve into a true platform technology.

METiS's proposed "Rocket + Satellite" model is essentially a response to this question. The “Rocket” refers to the nano-delivery system responsible for delivering drugs to target tissues, while the “Satellite” represents different therapeutic payloads. Unlike traditional delivery companies, Jitai aims to use AI to enhance the R&D efficiency of this "Rocket."

METiS's core platform, NanoForge, is its AI-driven nanodelivery platform that encompasses molecular generation, property prediction, AI-guided iterative cycles of dry and wet lab experiments, as well as lipid formulation design and optimization, further yielding solutions such as AiLNP and AiRNA. In essence, AI is not merely an add-on feature but is embedded throughout the entire process of nanomaterial discovery, delivery system design, and experimental optimization.

This means that METiS aims to address not merely the question of "how to deliver a single mRNA drug," but rather whether AI can be leveraged to continuously identify more suitable delivery materials and strategies, and then replicate the validated delivery capabilities across different tissues, cell types, and therapeutic payloads. Following this logic, switching to mRNA, TCEs, or even other immunomodulatory molecules could enable entry into different disease therapeutic areas. Consequently, the key factor to monitor is no longer the success or failure of any single pipeline, but whether this "AI + delivery" technology platform can be consistently replicated.

Within this framework, MTS-109 represents a pipeline worth singular attention for METiS TechBio. The company positions it as an mRNA-encoded trispecific T-cell engager (TCE). Its core strategy leverages differentiated delivery to enable mRNA to enter lymphoid organs and express therapeutic molecules in vivo, thereby exploring more profound B-cell depletion capabilities. Compared with the direct administration of traditional TCEs, MTS-109 aims to address not only "what is produced," but also "where it is produced, for how long, and whether it can penetrate deep into immune tissues."

At a recent speech at the "Major Country's New Drugs" event hosted by Tongxieyi, Lai Caida further disclosed some of the R&D strategies behind MTS-109. Targeting the vast market for autoimmune diseases, Metis Therapeutics aims to address a key pain point: achieving both favorable safety profiles and effective depletion of deep-tissue B cells in outpatient settings. To this end, Metis has designed a delivery system capable of expressing proteins within lymphoid organs, benchmarking MTS-109 against technological approaches such as in vivo CAR-T therapy.

According to Lai Caida's disclosures in his presentation, in non-human primate studies, MTS-109 was administered at doses significantly lower than those of the benchmark regimen, yet profound B-cell depletion was observed in tissues such as lymph nodes, bone marrow, and spleen. He further revealed that the company observed a high degree of depletion following the first dose, suggesting that this result may open new avenues for research into "immune reset" strategies for autoimmune diseases. However, these findings and interpretations currently remain at the preclinical R&D stage; considerable validation is still required before clinical efficacy can be established and before the concept of "immune reset" can be confirmed to translate into tangible patient benefits.

If this technological approach is ultimately validated in clinical settings, its significance may extend beyond MTS-109 itself. Autoimmune diseases currently rely heavily on long-term medication and continuous immunosuppression. The ability to achieve deeper and more durable B-cell depletion suggests a potential shift in treatment paradigms from long-term disease control to prolonged remission or even immune reconstitution. This is why in vivo CAR-T, mRNA-TCE, and other technologies are increasingly targeting this market.

More importantly, MTS-109 serves as a validation of METiS TechBio's "rocket + satellite" model: if the delivery platform itself is reusable, the next "satellite" does not necessarily have to be a TCE.

METiS TechBio is currently expanding the application of mRNA-TCE to solid tumors through projects such as MTS-105. Although the two projects target different disease indications, from a platform perspective, the core challenge remains consistent: leveraging differentiated delivery strategies to deliver diverse mRNA payloads to the precise sites where therapeutic efficacy is required.

This is also the core distinction between platform-based biotech companies and single-pipeline firms. What platform enterprises ultimately need to demonstrate is not merely the efficacy of a single candidate drug, but the sustained stability of their underlying delivery and expression capabilities even when the payload, indications, and mechanism of action are changed. If this closed loop is truly validated, the value of the platform ceases to be a simple sum of its individual pipelines; instead, it becomes a foundational capability that can be leveraged repeatedly for subsequent new drug development.

Of course, neither Novartis's bet on ABO2203 nor METiS TechBio's MTS-109 and MTS-105 has yet proven that this platform logic is fully established. mRNA-TCEs remain in the early stages of clinical development, and it still requires more clinical data to verify whether delivery systems can achieve stable, precise, and reproducible targeted delivery in humans. Novartis's potential deal, worth up to $7.775 billion, appears more like a preemptive wager by capital and industry on this technological direction rather than a confirmation of its commercial success.

But the industrial changes have already occurred.

A head of business development at a multinational corporation told VCBeat that the industry is currently witnessing a clear trend: multinational pharmaceutical companies are shifting their approach to sourcing Chinese innovations from seeking individual original Chinese molecules to identifying foundational technological capabilities capable of continuously generating new molecular entities.

This may well be the more significant signal for Chinese innovative pharmaceutical companies to heed behind the $7.2 billion deal.

As mRNA enters the era of in vivo immune engineering, the core of competition may no longer be just "how many types of proteins mRNA can encode," but whether it can be precisely delivered to the locations in the human body where it is truly needed.

For METiS TechBio, the critical question has shifted from "Is there an MTS-109?" to a broader one: Can an AI-driven nanodelivery platform enable a single "rocket" to continuously carry different "satellites," and ultimately, can clinical data demonstrate that this platform is reproducible?

If this premise holds, what multinational pharmaceutical companies may revalue is no longer just isolated Chinese innovative molecules, but rather underlying technology platforms capable of continuously generating new drugs by integrating AI-driven design, mRNA sequences, precise delivery systems, and therapeutic payloads.