About InCephalo
Developing Compartment Locked
(C-Locked) therapeutics
InCephalo develops exclusively local treatments for neurological diseases, with a focus on cancers in the brain (primary brain cancers as well as secondary brain cancers). The proprietary Compartment Lock technology, also called C-Lock, retains biologics, that are applied locally behind the blood brain barrier, in the central nervous system (CNS) and once they leave the CNS, degrades them rapidly in the systemic compartment. Thereby it significantly improves local CNS therapy, a challenging task with regards to achieving high local concentration (for efficacy) and low systemic footprint (to reduce potential side effects). Especially the peripheral side effects still limit various promising candidates for the treatment of brain cancer or other neurological diseases.
These often arise from high systemic exposure after intravenous administration of the drug as only 0.1% – 2% enter the brain. Locally applied C-Locked biologics stay in the brain and, even if they should leak, are rapidly degraded, thus offering a much-improved therapeutic window.
Medical Challenge
One of the biggest challenges for CNS (brain) therapies is getting the drug into the brain and for the drug to remain at high concentration at the disease site.
Our Approach
First tailor-made biological drugs for application behind the blood brain barrier
InCephalo‘s Compartment Lock technology, also called C-Lock, allows tailor-made molecules for local administration. These have two (2) properties: (i) they stay in the desired compartment for an extended period of time, and (ii) if they leak, they are rapidly degraded. The combination of both properties will significantly reduce the drug’s overall exposure to the body and allow for a higher local dosing window with considerably reduced chances for adverse events in other parts of the body.
The technology can be applied to antibodies, Fc-fusion proteins and similar biological drug formats.
C-Locked pipeline
InCephalo has an IP portfolio revolving around its Compartment Lock technology. This toolbox allows to create tailor-made molecules for local application of drugs behind the blood brain barrier.
InCephalo’s drug discovery team is currently applying the C-Lock technology on a variety of established and promising new targets for novel therapies of cancers in the brain.
First drug candidate - InC01
InC01 (IL-12)
InCephalo’s Compartment Locked IL-12 cytokine (InC01) is a locally applied biological drug candidate designed for the treatment of cancers in the brain. It was awarded Orphan Drug Designation by EMA.
IL-12 is a potent proinflammatory cytokine and a master regulator of a robust anti-tumor immune response. It can transform the “cold” immunsuppressive brain tumor microenvironment into an inflammatory “hotspot”. It has shown treatment efficacy in countless preclinical models alone or in various combination regimens and encouraging signs of efficacy in first-in-human trials.
Generously provided by Prof. Hutter, University Hospital Basel
Nevertheless, one of the biggest challenges for IL-12 treatments is that it is poorly tolerated in the blood of patients. Both intravenous application (approach (i)) and local application (approach (ii)) are leading to substantial systemic exposure. Resulting peripheral dose limiting toxicity precludes reaching sufficient local concentration in the tumor to trigger a similar efficacy as seen in preclinical studies. In contrast to current approaches, InC01, InCephalo’s C-Locked IL-12 cytokine is better retained at the tumor and if it leaks into the bloodstream, is rapidly degraded. This expanded dosing window now allows physicians to use the optimal dose without the constraints of systemic toxicity.
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