Chiesi Group and Key2Brain announced a worldwide licensing agreement to advance the development of blood-brain barrier (BBB)-crossing recombinant enzyme replacement therapies for lysosomal storage disorders, including alpha-mannosidosis and Krabbe disease. The collaboration targets ultra-rare diseases that affect the central nervous system and represent areas of profound unmet medical need.
The agreement builds on an existing research collaboration initiated in 2022 that aimed to develop the production of a BBB-crossing recombinant alpha-mannosidase. The partnership has been supported by positive in vivo proof-of-concept data demonstrating the potential of Key2Brain's proprietary technology platform.
Strategic Partnership Framework
Under the terms of the agreement, Key2Brain will provide Chiesi Group with a worldwide, royalty-bearing license to develop and commercialize two BBB-crossing enzyme replacement therapies. Key2Brain will receive an upfront payment and is eligible to receive development and sales-based milestone payments and tiered royalties on potential sales. Chiesi Group will fund all research, development, and subsequent commercialization worldwide.
The agreement also includes a framework for the parties to include additional enzymes into the collaboration, enabling the expansion of Chiesi's BBB-crossing ERT portfolio. There is also a possibility, upon mutual agreement, for the parties to expand the license to Key2Brain's BBB-crossing technology platform for the development of additional BBB-crossing ERTs.
"At Chiesi Global Rare Diseases, we are deeply committed to building a sustainable pipeline in rare diseases by embracing emerging technologies that can enhance the treatment landscape," said Giacomo Chiesi, Executive Vice President, Chiesi Global Rare Diseases. "This agreement exemplifies that vision—working to address areas of profound unmet medical need, including neurodegenerative manifestations of ultra-rare diseases like alpha-mannosidosis and Krabbe disease. For too many families, there are still no therapeutic options. Our goal is to bring them hope where today there is none."
Technology Platform and Therapeutic Approach
Key2Brain's technology enables efficient brain uptake and broad distribution of therapeutics, utilizing small (<15kDa) engineered single domain VHH antibodies with monovalent specificity for the Transferrin Receptor (TfR). The technology provides opportunities for the development of next generation brain targeting across a diverse range of therapeutic areas.
The VHH technology can be efficiently integrated into or combined with therapeutic molecules without impacting either the disease target specificity, or the binding of transferrin to TfR. The modular and flexible platform is being applied to peptides, proteins, enzymes, and oligonucleotides.
"By combining our deep therapeutic expertise with Key2Brain's proprietary BBB-crossing platform technology, we aim to enhance the biodistribution, efficacy and tolerability of promising therapies that have historically faced challenges reaching the central nervous system," said Mitch Goldman, Senior Vice President R&D, Chiesi Global Rare Diseases. "Together, our goal is to unlock new therapeutic pathways for patients with lysosomal storage disorders, ultimately delivering meaningful and lasting innovation."
Development Programs and Clinical Applications
The collaboration leverages Key2Brain's proprietary BBB-crossing platform technology and Chiesi Global Rare Diseases' capabilities and expertise in the ultra-rare disease landscape, creating a path to advance the ongoing aMann-K2B program as well as initiate new preclinical programs that apply Key2Brain's technology to other lysosomal storage disorders.
Key2Brain's VHHs can be expressed in both prokaryotic and eukaryotic systems and purified using commercial large-scale affinity purification systems. The proprietary platform includes species cross-reactive (human/primate/mouse) as well as human/primate specific binders together with a humanized TfR mouse model for translational studies.
"Expanding our relationship with Chiesi Global Rare Disease allows us to build on a clinically validated foundation to address the neurological complications of lysosomal storage disorders, including alpha-mannosidosis and Krabbe disease," said Elisabet Sjöström, Ph.D., Founder and CEO, Key2Brain. "Through this agreement, we aim to accelerate the research of potential breakthrough therapies that address these neurodegenerative conditions. We believe this partnership serves as a testament to the versatility and competitiveness of our BBB-crossing technology, unique features that are being utilized in Key2Brain's development of our proprietary next-generation brain-targeting therapies."
The advancement of these programs will contribute to Key2Brain's goal of establishing its technology as a leading BBB-crossing platform. At Chiesi Group, these programs are spearheaded by Chiesi Global Rare Diseases, the Group's dedicated business unit focused on research, development, and commercialization of therapies for rare and ultra-rare conditions.
