The race to develop effective therapies for central nervous system (CNS) diseases has never been more intense. The past year has seen a flurry of major deals, collaborations, and landmark research breakthroughs, signaling a clear market focus on one of the biggest hurdles in medicine: successfully delivering therapeutics across the blood-brain barrier (BBB).
Strategic moves by major players highlight this critical pain point. For example, AbbVie acquired Aliada Therapeutics for $1.4 billion, a company with a delivery platform based on TfR1 and CD98hc, focusing on brain diseases like Alzheimer's [1]. GSK partnered with ABL Bio to use its IGF1R-targeting BBB platform Grabody-B to develop therapies for Alzheimer's and Parkinson's disease [2]. AstraZeneca’s Alexion secured a non-exclusive license for JCR Pharmaceuticals’ JUST-AAV platform, known for its high-efficiency BBB delivery capability, with an investment of $825 million[3]. These developments, along with others in the field, show that the industry is betting big on BBB-crossing platforms to get large molecules to their CNS targets.
| Date | Company | Delivery Platform | Target | Therapeutic Modality | Key Information (Deal & Research) |
|---|---|---|---|---|---|
| 2024/10/28 | AbbVie | MODEL® | TFR1&CD98HC | Antibody | AbbVie acquires Aliada Therapeutics for $1.4B to focus on brain diseases like Alzheimer's. The platform also includes a BBB-penetrating anti-Aβ antibody, Alida-1758. |
| 2025/1/7 | Sanofi | AntiClastic | / | ASO | Sanofi partners with Alloy Therapeutics on a CNS drug project. Sanofi acquires non-exclusive rights to the AntiClastic platform and a $400M investment. The platform is used to develop treatments for neurological and neurodegenerative diseases. |
| 2025/4/7 | GSK | Grabody-B | IGF1R | Antibody, ASO, siRNA | GSK collaborates with ABL Bio, utilizing the IGF1R-targeting Grabody-B BBB platform to develop treatments for Alzheimer's and Parkinson's disease. |
| 2025/7/8 | AstraZeneca | JUST-AAV | TFR1 | AAV | Alexion, a subsidiary of AstraZeneca, obtains non-exclusive development rights for JCR Pharmaceuticals' JUST-AAV platform for $825M. The platform has high-efficiency BBB delivery capability to advance gene therapy. |
| 2025/7/9 | Novartis | BDM | / | Antibody, Gene Therapy | Novartis acquires Vesalius Therapeutics for $120M, focusing on neurological, neurodegenerative, and rare diseases. Its BDM platform has high-efficiency BBB delivery capability. |
| 2025/7/16 | Acumen | J-Brain Cargo® | TFR1 | Antibody | JCR Pharma and Acumen expand their CNS drug discovery and development collaboration by co-developing novel neurodegenerative disease treatments using JCR's J-Brain Cargo® platform. |
| 2025/7/22 | Denali Therapeutics | Dual ATV | TFR1&CD98HC | Antibody, ASO, siRNA | Denali Therapeutics announces a collaboration for its Dual ATV platform, worth up to $2.25B, to advance CNS and neuromuscular disease treatments. |
| 2025/7/28 | Roche | BrainshuttleTM | TFR1 | Antibody | Roche announces impressive clinical data for Trontinemab (Brainshuttle™), a BBB-penetrating Aβ antibody. The highest dose group showed 91% of patients became Aβ-PET negative within 28 weeks, with an ARIA-E incidence of <5%, validating the platform's potential. |
| 2025/8/5 | Dyne Therapeutics | FORCE™ AOC | TFR1 | ASO | Dyne Therapeutics' DYNE-251 receives FDA Fast Track designation for DMD. Its platform uses a TfR1-targeting Fab to achieve precise distribution in muscle tissue. |
| 2025/8/6 | Novartis | AOC | TFR1 | ASO, siRNA | Reportedly, Novartis is considering acquiring Avidity Biosciences, a company leveraging a TfR1-targeting antibody platform (AOC) to deliver RNA therapeutics to muscle and nervous tissues. |
| 2025/8/7 | Biogen | ATV:cisLALA | TFR1 | Antibody, ASO, siRNA | In a *Science* article, a study shows that the ATV:cisLALA platform effectively eliminates ARIA side effects while enhancing the safety and stability of CNS drug delivery. |
| 2025/8/11 | University of South Carolina | T-CeNP | RAGE | Antibody | A research team at USC built a T-CEnP BBB-crossing platform that can improve the delivery of anti-oxidative and neuroprotective factors to treat Alzheimer's disease by reducing oxidative stress and inflammation. |
| 2025/8/13 | Galibra&Emugen | TFR1 CapX | TFR1 | AAV | Apertura Gene Therapy licenses its TfR1 CapX platform to partners like Galibra and Emugen to enhance gene therapy delivery efficiency in the brain, aiming to conquer complex neurological diseases. |
The BBB is a highly selective "fortress" composed of tightly packed brain endothelial cells, astrocytes, pericytes, and a basement membrane, which acts as a defense system to protect the brain from pathogens and toxins[7].
To overcome this bottleneck, scientists have developed various BBB-crossing strategies, with the non-invasive receptor-mediated transcytosis (RMT) mechanism being one of the most promising[10]. Ideal RMT targets are highly expressed on brain endothelial cells but have low expression in the periphery to minimize side effects. While no single perfect target exists, TfR1 and CD98hc have become mainstream focuses. Platforms from companies like Roche, Aliada, and Denali conjugate therapeutic molecules to antibodies targeting TfR1 or CD98hc, using the receptors' transport to "shuttle" drugs from the blood into the CNS, thereby improving brain exposure and therapeutic effect.
A major challenge with these platforms is that many human-specific therapeutics cannot bind to or cross the mouse BBB due to species differences. For instance, many human-targeting TfR1 platforms cannot bind to rodent TfR1 or cross the mouse BBB[11-12]. To address this, Cyagen has developed a suite of novel humanized mouse models for BBB research. Our models are engineered to express key human BBB targets, including TfR1, CD98hc, IGF1R, and RAGE, allowing you to accurately test your human-specific therapeutics in vivo.
Our B6-hTFRC(CDS) mouse is a prime example. This model specifically expresses the human TfR1 protein, not the mouse version. It's an ideal tool for evaluating antibody-based platforms that use TfR1 as a molecular "trojan horse". We also offer disease-specific humanized models for conditions like Alzheimer's, Parkinson's, and ALS.
| Product NO. | Strain Name | Target | Type | Condition |
|---|---|---|---|---|
| C001584 | B6-hTFRC(CDS) | TFRC (TFR1) | BBB Delivery Targets | Available |
| C001840 | B6-hFcRn/hTFRC | TFRC (TFR1) & FcRn | Available | |
| C001730 | B6-hALB/hTFRC | TFRC (TFR1) & ALB | Available | |
| C001608 | B6-hC3/hTFRC(CDS) | TFRC (TFR1) & C3 | Available | |
| TBD | B6-hTFRC(Genomic) | TFRC (TFR1) | R&D | |
| C001623 | B6-hIGF1R | IGF1R | Available | |
| C001624 | BALB/c-hIGF1R | IGF1R | Available | |
| TBD | B6-hCD98HC | CD98HC | R&D | |
| TBD | B6-hRAGE | RAGE | R&D |
The BBB-crossing field is an active "battleground" for neurodegenerative diseases. For example, Roche’s new-generation Aβ antibody, Trontinemab, has shown impressive clinical data [5]: the highest dose group showed 91% amyloid clearance at 28 weeks. This highlights the huge potential of TfR1-targeting platforms in neurodegeneration [13].
| Aβ Monoclonal Antibody Drug | Company | Anti-TFR1 | Complete Amyloid-β Clearance | Time to Efficacy | ARIA-E Risk |
|---|---|---|---|---|---|
| Trontinemab | Roche | √ | 91% (28 weeks) | ~8 weeks | <5%< /td> |
| Leqembi | Eisai/Biogen | × | 68% (18 months) | ~6 months | ~13% |
| Donanemab | Eli Lilly | × | 71% (12 months) | ~3 months | ~24% |
Beyond CNS, TfR1’s high expression in muscle cells also allows for efficient delivery to muscle tissue. Companies like Dyne Therapeutics and Avidity Biosciences are using TfR1-based platforms to target rare muscular diseases like muscular dystrophy and Pompe disease. The potential of BBB-crossing technology extends to other fields as well, including B-cell-related autoimmune diseases like multiple sclerosis.
The BBB-crossing revolution demands a robust "model toolkit" for accurate validation and optimization. At Cyagen, we have proactively built a comprehensive suite of humanized models to support this research, including:
- Humanized Models for BBB Targets: TfR1, CD98hc, IGF1R, and RAGE.
- Disease-Specific Humanized and KO Models: For AD, PD, ALS, MS, DMD, and SMA.
We are committed to providing systematic in vivo efficacy evaluation solutions, helping you remove interspecies translational barriers and accelerate your innovative drug discovery process.
At Cyagen, we understand that providing the right model is just the first step. Our comprehensive Neuro-CRO platform is designed to support your research from start to finish, providing a one-stop solution for preclinical studies. Our services include:
- CNS Disease Model Creation and Breeding: From genetically engineered to induced disease models, tailored to your specific research needs.
- In Vivo Pharmacological Efficacy Evaluation: We help you validate your drugs against a wide range of CNS and neuromuscular disease models.
- Behavioral & Cognitive Assessment: Utilize our state-of-the-art facilities for behavioral testing to measure the therapeutic effects of your compounds.
- Histopathology & Biomarker Analysis: Gain deeper insights through our expertise in tissue staining, imaging, and biomarker analysis.
By combining our advanced models with a full suite of research services, we help you remove common obstacles and accelerate your path to clinic.
[1] AbbVie. (2024, October 28). AbbVie to acquire Aliada Therapeutics, strengthening focus in Alzheimer’s disease and neuroscience pipeline. Retrieved from https://news.abbvie.com/2024-10-28-AbbVie-to-Acquire-Aliada-Therapeutics,-Strengthening-Focus-in-Alzheimers-Disease-and-Neuroscience-Pipeline
[2] ABL Bio. (2025, April 7). ABL Bio announces Grabody-B brain delivery platform license agreement with GSK to develop novel medicines for neurodegenerative diseases.
[3] Pharmaceutical Technology. (2025, July 9). JCR Pharmaceuticals and Alexion partner on JUST-AAV gene therapy platform. Retrieved from https://www.pharmaceutical-technology.com/news/jcr-pharmaceuticals-alexion-just-aav-gene-therapy-platform/
[4] Reuters. (2025, August 6). Novartis weighs deal with biotech Avidity Biosciences – FT reports. Retrieved from https://www.reuters.com/business/healthcare-pharmaceuticals/novartis-weighs-deal-biotech-avidity-biosciences-ft-reports-2025-08-06/
[5] Genentech. (2025, July 27). Interim biomarker results for trontinemab, a novel Brainshuttle™ antibody in development for the treatment of Alzheimer’s disease.
[6] Apertura Gene Therapy. (2025, August 13). Apertura licenses blood-brain barrier-penetrant AAV capsid to multiple partners advancing CNS treatments.
[7] Terstappen GC, Meyer AH, Bell RD, Zhang W. Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021 May;20(5):362-383.
[8] Wu D, Chen Q, Chen X, Han F, Chen Z, Wang Y. The blood-brain barrier: structure, regulation, and drug delivery. Signal Transduct Target Ther. 2023 May 25;8(1):217.
[9] Jankovic J, Goodman I, Safirstein B, Marmon TK, Schenk DB, et al. (2018). Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2018 Oct 1;75(10):1206-1214.
[10] Haqqani AS, Bélanger K and Stanimirovic DB (2024) Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria. Front. Drug Deliv. 4:1360302.
[11] Metin Yesiltepe, et al. (2025). Humanized TfR1 and transferrin gene-replacement rats for in vivo evaluation of BBB transport. bioRxiv. doi: 10.1101/2025.07.25.666792.
[12] David M, Cohen R, Beuzelin D, et al. (2025). Identification and optimization of trans-species reactive TfR1-binding VHH as tools for drug delivery across the blood-brain barrier. bioRxiv. https://doi.org/10.1101/2025.05.23.649291v1
[13] Alzheimer’s Weekly. (2025). Trontinemab: A new hope for Alzheimer’s. Alzheimer’s Weekly.
[12] David M, Cohen R, Beuzelin D, et al. (2025). Identification and optimization of trans-species reactive TfR1-binding VHH as tools for drug delivery across the blood-brain barrier. bioRxiv. https://doi.org/10.1101/2025.05.23.649291v1
[15] Denali Therapeutics. (2025). Crossing Barriers and Defeating Degeneration: Corporate Overview – March 2025. Investor Relations, Denali Therapeutics.
[16] Dyne Therapeutics. (2025). Our FORCE™ Platform. Dyne Therapeutics.
[17] Avidity Biosciences. (2025). Pipeline Overview. Avidity Biosciences.
[18] Genentech. (2025). RG6035 BrainShuttle™ CD20. Genentech Pipeline for Medical Professionals.
