Vector Approaches To Reaching CNS Targets With Vect-Horus' Jean-Manuel Péan
A long-standing challenge in delivering therapeutic treatments for CNS (central nervous system) disorders is how to overcome drug permeability constraints imposed by the blood-brain barrier (BBB). In this episode of Supplier Horizons, host Tom von Gunden talks with Chief Scientific Officer Jean-Manuel Péan from Vect-Horus, a developer of vector-based, platform delivery technologies, about addressing that challenge in targeting disorders such as autism, dementia, Alzheimer’s, epilepsy, Parkinson’s, Huntington’s, sclerosis, and CNS tumors.
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Episode Transcript
Tom von Gunden, Chief Editor, Drug Delivery Leader:
Welcome to another episode of Supplier Horizons, where we hear about innovations being worked on by suppliers to the drug delivery industry. My name is Tom von Gunden, Chief Editor of Drug Delivery Leader and your host for the series. Today I am joined by Jean-Manuel Péan, who is Chief Scientific Officer at Vect-Horus, which is a company working on platform technologies specifically targeting central nervous system, or CNS, conditions or diseases, and specifically working on the challenges of crossing the blood-brain barrier [BBB].
So, for that conversation, I want to welcome you, Jean-Manuel.
Jean-Manuel Péan, Chief Scientific Officer, Vect-Horus:
Thank you.
Well, thanks for joining me. Let's just go ahead and dive right in. So, I know that, as I mentioned in the intro, the company is working on platform technologies to address CNS [central nervous system] and get over the blood-brain barrier to do that. So, can you talk a little bit about, generally speaking, what opportunities are out there to do that work?
Okay. I would say that CNS disorders — I don't know if you know — but they are the leading cause of illness and disability in the world: autism, dementia (mainly Alzheimer's disease), epilepsy, sclerosis, neurodegenerative conditions like Huntington's or Parkinson's disease, and, of course, CNS tumors. [These] often cannot be cured with current therapeutic options, which also have a dramatic impact on quality of life for patients but also for their families.
I would like to provide some figures on these conditions to illustrate the scale. Regarding the number of new cases of CNS tumors in 2045, a 47% increase is projected from the number of cases in 2022, assuming [an] unchanged incidence rate. And this was published recently, in 2025, in the Journal of Neuro-Oncology. In 2021, 57 million people worldwide suffer from dementia, and this is expected to grow three times by 2050. This was also published this year in BMC Public Health. And in the same article, it was also pointed out that the economic cost of dementia is likely unsustainable for healthcare systems if the numbers of people living with dementia rise as projected. Finally, I would add that family caregivers of dementia patients are significantly more likely to experience anxiety and depression.
Okay, so fortunately, modern drug modalities bring, of course, new therapeutic options in the hope that these have significantly higher molecular mass, higher hydrophilicity, and higher degrees of complexity compared to the classical small, organic molecules. And then they have dramatically lower cell permeability and membrane permeability.
For instance, if we focus on monoclonal antibodies, it is generally recognized that the brain concentration of most therapeutic antibodies, like [those] recently approved for Alzheimer's disease, is only 0.1% of a concentration in the blood. So, a recent study from the consulting firm BCG explained that, between 2019 and 2023, half of all new modalities failed at the preclinical and clinical stage.
Okay, of course, some of these drugs failed because they are not effective or safe enough. But all too often, the reason is that they do not reach the disease targeted organ, especially in the case of a CNS, which is isolated by the so-called blood-brain barrier.
It is exactly why drug delivery scientists are working on targeted drug delivery technologies. These technologies, such as the one developed by Vect-Horus, called VECTrans®, aim to increase permeability and drug exposure in disease target tissues. And they have potential to significantly improve the biopharmaceutical performance and clinical development of life-saving drugs for CNS disorders and CNS cancers.
Gotcha. Well, thank you for talking about the market out there and how you're targeting it. So, let's get into the technology more specifically. So, I know that what you've described is a platform. And so, it's delivering something to those folks with CNS conditions.
Can you tell us a little bit about the route of administration? How does what you're delivering get there? And then, what's the mechanism of action in the patient's body once the drug or biologic is received?
Of course. So first, you should know that the wall of blood microvessels in the brain and spinal cord has very poor permeability compared to other organs. It is made of endothelial cells connected by junctions and covered by other cells, like glial cells. And this multilayer membrane is the interface between the blood and the blood-brain barrier, the so-called BBB.
And the BBB has a dual function: first, to protect the brain, probably more than other organs against toxic compounds and pathogen. And second, to provide nutrients for the brain through a highly selective transport system using transporters and receptors. And, as a consequence, the BBB prevents therapeutics, including drugs, from entering the brain unless very high doses are administered, but with subsequent toxicity issues.
So, to overcome the BBB and efficiently deliver therapeutic agents to the brain, drug delivery experts have very few options: local administration, like intraparenchymal, has some advantages, but it is also highly invasive. In addition, drug diffusion from the injection site is poor, without possibility to distribute widely within the parenchyma.
The second option: nose-to-brain delivery, where an intranasally administered drug is believed to reach some areas of the brain by following olfactory and trigeminal nerves, but with high variability.
The third option: transient permeabilization of the BBB, for instance, by ultrasound and microbubbles. However, such strategies that fully open the BBB also [allow] toxins and pathogens to enter the brain.
And finally, the last possibility: It's to design a ligand-based system, like the vectors developed by Vect-Horus.
So, let me explain ligand-based system. Ligand-based systems involve conjugating the drug substance of interest to a targeting ligand, which can bind to receptors or transporters naturally, highly expressed at the surface of the BBB, such as, for instance, the transferrin receptor. So, after IV or SubQ [subcutaneous] administration, the drug conjugate circulates within the blood, binds to the targeted receptor, and then is transported across the BBB in the same way as an endogenous ligand.
So, the latest advances in receptor-mediated transport like that focus on the relationships between binding affinity to the receptors, intracellular trafficking, and then transit efficiency. And also on the discovery of highly specific ligands with small size and that do not compete with endogenous compounds.
Vect-Horus is targeting ligands. Vect-Horus is focusing on small antibody fragments known as VHH. And these small antibody fragments are derived from heavy chain-only camelid antibodies.
They exhibit numerous advantages: They are small proteins, highly stable, highly soluble, with low immunogenicity. They are easy to manufacture. They have a species cross-reactivity, and that is very important to ensure efficient translation from research into clinics.
That is the VECTrans® technology.
Well-done on describing how things are moving into the body and what happens once they're there. Thanks for the background and the detail.
So, to move those advancements forward — the platform approaches — and get that science that you just described happening, I'm sure there's work that's being done internally at Vect-Horus on innovation. But I'm also sure there's some [external] partnering that's happening as well. So, can you talk about how things actually move forward internally, as well as with partners?
Exactly. So, Vect-Horus focuses definitively on research and innovation. And we bring together, within the company, experts in pharmacology, biotechnology, and conjugation chemistry. So, we establish, classically, proof-of-concept in animals, showing that all targeting ligands can deliver in particular radionuclides, peptides, oligonucleotides, and antibodies across the BBB.
And our business model is based on co-development and partnership agreements with pharma and biotech companies, which run the preclinical and clinical development for their products with our vectors. For instance, RadioMedix, Novo Nordisk, and Ionis Pharmaceuticals all have exclusive global licenses to use our technology to deliver their products directed against specified therapeutic targets. In total, Vect-Horus currently has more than ten active partnerships.
Great. And as that work proceeds — as you look toward the near horizon and the far horizon, whichever is more relevant in terms of this question — what are some of the key problems that still need to be addressed, challenges to address, questions to answer? What's ahead that needs to be focused on to continue these advancements?
Like I said at the beginning, there are a few different options to achieve targeting brain delivery of drug compounds. And, actually, the ideal situation would be to combine all of the advantages of the different approaches and to reach the following, target product profile [TPP]: First, the possibility to achieve high drug concentration within the CNS to improve drug efficiency, yet with administration of low doses by a noninvasive route. [Second], a perfect site-specific distribution to avoid any off-target toxicity. And last point: a prolonged duration of action to reduce the number of administrations.
And so, with this goal in the field of ligand-mediated technologies like that of Vect-Horus, the next step is mainly to identify new receptors or transporters with even higher organ-specificity. And this will improve the selectivity and the efficiency of the targeting.
And also, I would say that current research on drug-targeting focuses not only on targeting an organ, but also on achieving functional targeting delivery in a specific subpopulation of cells to be treated within the organ. For instance, within the brain, how to treat the astrocytes or the glial cells or the neurons.
Great, great. So, I just have one last question for you today, Jean-Manuel, and that is: If these advancements that you're working on there — the folks are working on, in partnership and in the company itself — if they move forward, as anticipated, how do you envision the lives and health of patients to be different once those advancements have landed? What benefits do you think folks will derive from them?
Once again, Vect-Horus technology is enabling our partners, who are discovering and developing modern therapeutic agents, to bypass the BBB and overcome a major obstacle to the development of life-saving drugs for CNS disorders, including degenerative diseases and cancer.
So, under our partnership with RadioMedix, one theranostic agent that uses our technology is already in early clinical stage for the treatment of brain tumors. And further clinical trials with other partners are expected to start in 2026, paving the way to new treatment alternatives for how to treat diseases. Ultimately, I would say that the aim and hope of all researchers within Vect-Horus is to enable the really significant improvement in treatment of patient conditions.
I want to thank you, Jean-Manuel, for joining me for this episode of Supplier Horizons. And to our audience, I want to thank you for joining us as well. And we'll see you next time.