The properties of the blood-brain barrier serve a vital protective role, but they also keep drugs from reaching the organ. Big pharmaceutical companies have been making deals for technologies that could help them get their molecules through this protective membrane and now GSK is joining in, striking up an alliance that gives it a new way to shuttle drugs into the brain to treat neurodegeneration.
The agreement announced Monday gives GSK access to a platform technology developed by ABL Bio. Specific diseases covered by the pact were not disclosed. The deal kicks off with GSK paying South Korea-based ABL £38.5 million (about $49.1 million) up front.
The drug delivery approach of ABL is based on Grabody, a platform technology that develops bispecific antibodies, proteins engineered to bind to two targets. For treating brain diseases, the bispecific antibodies from Grabody contain a domain designed to bind to insulin-like growth factor 1 receptor (IGF1R), a receptor that transports proteins across the blood-brain barrier. The other binding domain is designed to go after the desired target for treating a brain disorder.
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GSK and ABL aren’t disclosing the brain targets they’re pursuing. But the agreement covers multiple programs for novel targets that could be treated with various therapeutic modalities. For example, they say an ABL brain drug could be used to deliver genetic medicines to the brain, such as small-interfering RNA drugs or antisense oligonucleotides.
ABL’s most advanced brain program is a Parkinson’s disease drug candidate in development under a partnership with Sanofi. The brain target of this preclinical drug, ABL301, is alpha-synuclein. While that protein is also the target of other Parkinson’s drug candidates, ABL contends the bispecific approach of its drug could more efficiently target alpha-synuclein compared to traditional monoclonal antibodies.
Under GSK’s deal, ABL will transfer to the pharma giant technology and know-how related to the Grabody-B platform. GSK will take on responsibility for preclinical and clinical development of drug candidates, along with manufacturing and potential commercialization. Depending on the progress of the research, ABL could receive up to £2.075 billion (about $2.6 billion) in milestone payments, plus royalties if any drugs resulting from the collaboration reach the market.
“Many of the most promising new therapies are antibodies, which cannot efficiently reach the brain without a shuttle to get them across the BBB (blood-brain barrier),” Christopher Austin, senior vice president of research technologies, GSK, said in a prepared statement. “This agreement reflects our commitment to innovative platform technologies to overcome the BBB and thus open entirely new opportunities for treating these devastating diseases, an important component of our emerging pipeline.”
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GSK already has clinical-stage Alzheimer’s disease programs from a partnership with Alector that began 2021. Latozinemab (formerly AL001) is in Phase 3 testing; Alector has said it expects preliminary data by the end of 2025. AL101 (also known as GSK4527226) is in Phase 2. Both drugs are monoclonal antibodies intended to reduce degradation of progranulin, a protein that regulates immune activity in the brain.
The targeting of a receptor to deliver a therapy across the blood-brain barrier gives GSK another way to potentially treat neurodegeneration, but it’s not alone in this approach, called receptor-mediated transcytosis. The platform technology of Aliada Therapeutics engineers antibodies to target the transferrin and CD98 receptors to transport molecules across the blood-brain barrier. Similar to ABL, Aliada said its technology can be applied to multiple types of therapeutic cargos, such as enzymes, proteins, and oligonucleotides. With the biotech’s lead program in early clinical development for Alzheimer’s, AbbVie last year agreed to pay $1.4 billion to acquire Aliada.
ABL’s research also spans Grabody drugs in development for cancer. A partnership with I-Mab is developing PD-L1- and claudin 18.2-targeting drugs; both programs are in Phase 1 for solid tumors. The most advanced ABL program is ABL001 (also known as tovecimig), a VEGF-targeting drug in late-stage clinical development for biliary tract cancer among other cancer indications under a partnership with Compass Therapeutics.
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