From MNC Billion-Dollar Bets to First Breakthrough: BBB Delivery Technologies Reshaping CNS Therapeutics

Recently,AstraZenecaIts rare disease division Alexion and JapanJCR PharmaceuticalsReach a licensing agreement for the non-exclusive development rights of the latter's patented technology, JUST-AAV capsid platform. The agreement includes an upfront payment and totals up to $825 million. This marks the third collaboration between the two parties, following previous partnerships that utilized JCR Pharma's blood-brain barrier penetration technology, J-Brain Cargo.^®Development of innovative therapies for neurodegenerative diseases and application of this technology in the development of oligonucleotide therapies.

The key to achieving multiple collaborations lies in JCR Pharma's J-Brain Cargo.^®Technology Platform, this technology isFusing drug proteins to antibodies targeting the transferrin receptor, binds to the transferrin receptor on the endothelial cells of the blood-brain barrier, and then crosses the blood-brain barrier through receptor-mediated endocytosis, thereby achieving intracerebral delivery. The JUST-AAV capsid platform involved in this collaboration represents an innovative breakthrough based on the existing technology platform, capable of embedding within the AAV capsid.Small Anti-Transferrin Receptor（TfR）Antibody, achieving targeted TfR on the BBB to penetrate the blood-brain barrier.

And this technology platform has been validated in preclinical studies, showing an improvement in brain delivery efficiency in mice compared to traditional AAV9.Approximately 77 times, and safety has been significantly improved.

And this is not an isolated case, in the same month,NovartisAndSironax（Sironax）A collaboration was reached, granting Novartis an exclusive option to acquire its proprietary "Brain Delivery Module (BDM)" platform. Sironax (Beijing) Co., Ltd. is eligible to receive up to a total of$175 millionThe upfront and near-term payments. The platform is a differentiated blood-brain barrier penetrating technology designed to enhance the brain delivery efficiency of various forms of drugs.

Three months ago, a collaboration that could be deemed the largest in the CNS field since 2025 was just born.GSKandABL BioGSK Reaches Global Licensing Agreement to Leverage ABL Bio's Blood-Brain Barrier Delivery Technology Grabody-B for Developing New Drugs for Neurodegenerative Diseases(Including antibodies, polynucleotides, or oligonucleotides)`, the total amount of this transaction can reach up to`£2.075 billion(Approximately 19.6 billion RMB)。

The core of ABL Bio's core technology platform, Grabody-B, is the design of "bispecific antibody fragments" with dual functionality—one end targets highly expressed endothelial cells within the blood-brain barrier.Insulin-like Growth Factor 1 Receptor（IGF1R）, with the other end connected to the therapeutic molecule to be delivered(such as antibodies, protein drugs, or nucleic acid molecules). After binding to IGF1R, it will triggerEndocytosis of Blood-Brain Barrier Endothelial Cells, enabling larger therapeutic molecules to cross the blood-brain barrier and enter the brain.

These large transactions clearly indicate that industry giants are rapidly entering this field by partnering with biotechnology companies possessing cutting-edge technologies or through direct acquisitions. Meanwhile, it is evident that the giants are focused on..."Receptor-Mediated Endocytosis"The collective betting on mechanisms accelerates the clinical translation and validation of this technology. "The collaborative efforts and competition led by giants" can form multi-dimensional transformative momentum for the industry.

In addition to the strategic layout of large pharmaceutical companies, innovative drug companies focusing on blood-brain barrier delivery technology have also gained capital favor. These companies possess exclusive technical platforms, jointly completing the big puzzle of brain-penetrating delivery technologies.

In March this year, the up-and-coming TRIMTECH TherapeuticsCompleted a $31 million seed financing roundThe company is committed to leveraging the unique properties of the E3 ubiquitin ligase TRIM21 to develop TRIMTAC degrader molecules, which are potent, blood-brain barrier-penetrating molecules capable of selectively degrading protein aggregates associated with various diseases, for the treatment of severe neurodegenerative and inflammatory conditions.

Last June, in ChinaGajin BioCompleted a new round of financing, exclusively invested by Phase I of the Zhangjiang Life Health Industry Incubation Angel Fund. Charon Biologics focuses on drug conjugation and delivery technology, and is the first in China to develop antibody-small nucleic acid conjugate drugs. It has also developed the Brainferry peptide platform, which has the potential to assist macromolecular drugs, including small nucleic acids, in crossing the blood-brain barrier, bringing transformative treatment options for a broader range of neurodegenerative diseases.

Earlier, focusing on the third-generation in vivo self-assembled exosome delivery RNA nucleic acid drug technologyImaBioCompleted tens of millions of angel+ round financing. In September 2024, Professor Pei Zhong from the First Affiliated Hospital of Sun Yat-sen University presented the preliminary results of the IIT study on Aimabio's ER2001 injection at the joint EHDN and Enroll-HD conference.

ER2001 Injection isThe World's FirstAn investigational siRNA drug that achieves central nervous system targeted delivery by crossing the blood-brain barrier through intravenous administration and in vivo self-assembly of exosome-coated siRNA, and this study（NCT06024265）Also the first in a country outside Europe and America(China)Exploratory clinical trial for Huntington's disease.

Data obtained from IIT studies show that among 10 treated patients, there was a clear improvement in overall clinical scale scores, particularly in comprehensive improvements in total motor score, mental state, and cognitive function. The disease progression of all patients was either controlled or improved during the clinical study period, and the safety and tolerability of the ER2001 product were good.

Various drug forms, such as small molecules and large molecules, cross the blood-brain barrier through different innovative mechanisms, sparking technical exchanges and competition that accelerate technological iteration. The influx of capital into this field speeds up the formation of a positive cycle of "technological breakthrough - increased financing - pipeline expansion," laying a critical cornerstone for the leap from "limited drug options" to "precise delivery" in the treatment of central nervous system diseases.

In February this year, an article titled "Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system" reported a series of lipid nanoparticles capable of crossing the blood-brain barrier.（BLNPs）, used forDelivery of mRNA Molecules to the Central Nervous System。

Researchers systematically designed and synthesized six categories of 72 lipids capable of crossing the blood-brain barrier. Through optimization and screening, they obtained an MK16 BLNP lipid nanoparticle system, which is able toNestin（Caveolae）And γ-secretase（γ-Secretase）Mediated Transcellular ActionAchieving crossing the blood-brain barrier, thereby delivering mRNA to neurons and astrocytes throughout the brain, and demonstrating good results in mouse models.

On February 19, 2025, an article titled "Bioengineered protein nanocarrier facilitating siRNA escape from lysosomes for targeted RNAi therapy in glioblastoma" reported aNovel Ferritin Nanocarrier tHFn（+）, which can cross the blood-brain barrier and precisely target gliomas, providing a novel strategy for the efficient delivery of siRNA.

The research team is based on human heavy-chain ferritin（HFn）Naturally equipped with tumor recognition and blood-brain barrier penetration capabilities, tHFn obtained through design and modification.（+）Mutant vector. This vector can depolymerize and release siRNA under weakly acidic conditions within cells, while exposing positive charges to help siRNA escape from lysosomes, significantly enhancing intracellular delivery efficiency. In a mouse glioblastoma model, it successfully reduced the expression of tumor-related genes such as siTERT and siEGFR, effectively inhibited tumor growth, and demonstrated highly efficient delivery capability for various target siRNAs.

Researchers are tackling challenges from multiple dimensions, such as vector design, mechanisms of action, and delivery precision. Breakthroughs in these cutting-edge studies are opening up broader possibilities for blood-brain barrier delivery technologies. Frontier research serves as an inexhaustible source of动力 for subsequent technological platform innovation.

The blood-brain barrier was once an insurmountable "natural moat" in the treatment of central nervous system diseases. However, today, a complete chain of "technological breakthroughs – capital empowerment – clinical translation" is taking shape: from giants' multi-billion-dollar technological bets, to innovative pharmaceutical companies gaining capital favor through exclusive platforms, to laboratory breakthroughs in precise delivery using lipid nanoparticles and ferritin carriers. In the future, a variety of technologies will be able to achieve blood-brain barrier penetration, and pipeline development and drug commercialization will reach new heights.

Editor-in-Chief: Xun

Proofread by Xun

References:

1. Corporate official website and public information

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