The Trojan llama

Targeted radiotherapy - HER2+ breast cancer with brain metastases

Project from 2015 Allocated sum 481 000,00 €

Precirix (formerly Camel-IDS) is a private biopharmaceutical company, born in 2014 within the VUB (Vrije Universiteit Brussel). This start-up develops and manufactures precision radiopharmaceuticals based on llama-derived antibodies that deliver radioactive isotopes to cancer cells in a highly targeted manner.

The Foundation Fournier-Majoie and three Belgian Business Angels have worked in close collaboration with the VUB and the project leader, Professor Tony Lahoutte, to successfully complete the development of the company and their lead product, CAM-H2.

The Foundation has been supporting this project since 2015 and has allocated EUR 481,000.

 

Targeted radiotherapy, how does it work?
Like every cell, cancer cells make proteins that generate certain actions (dividing to grow, creating new blood vessels, blocking programmed cell death). On the surface of cancer cells, these proteins form specific receptors which vary according to the type of cancer and are present in greater or lesser quantity.

In targeted radiotherapy, nano-antibodies carry a radioactive charge (iodine, radium, lutetium, etc.) and act as a homing head targeting a particular receptor. Once found, they attach themselves to it, irradiate the cell and destroy its DNA.

 

Small but super fast
10x smaller than conventional antibodies, the very small size of nano-antibodies (on 1 mm, 1 million nano-antibodies are placed!) presents a series of advantages:

  • They circulate very quickly in the body. A few minutes after the injection, they already reach their target and if they don’t find anything, they are eliminated within a few hours by the kidneys,
  • They can attach themselves to very small cancer cells that are difficult to detect,
  • The radioactive load they can carry is therefore also very small but large enough to destroy the cancer cells.

 

Small but strong
The nano-antibodies derived from llamas are very stable and robust, they do not lose their load on their way to the target cells. In addition, their special shape allows them to hold onto the cancer cell very firmly. By attaching themselves in this way, they allow the radioactive agent to do its job in a very localized way and destroy the target cell.

 

Great hope against brain metastases
Another substantial advantage linked to its size is its ability to reach cancer cells that have arrived in the brain to develop. It should be noted that the vast majority of therapeutic molecules do not pass the natural blood-brain barrier that protects the brain from undesirable substances circulating in the blood. The Precirix nano-antibodies do, however, and can target these cells.

 

Theranostics = combining diagnosis and therapy
The Precirix nanobodies also have a theranostic application: they can combine diagnosis in the first instance and therapy in the second.

For the diagnostic part, a small amount of nano-antibodies loaded with a small amount of radioactive elements are injected that will be monitored and detected by imaging. The presence of the cancer cells is thus mapped out.

It is immediately apparent whether the radioactive elements remain attached to one spot (the surface of the cancer cells) or circulate without stopping and are eliminated by the kidneys.

By confirming the presence of cancer cells with the targeted receptors in this way, more radioactive nano-antibodies can be injected, which then destroy the targeted cells.

 

A promising first product candidate: CAM-H2
CAM-H2 was designed to target cancer cells overexpressing HER2 receptors (certain breast and gastroesophageal cancers). Encouraging results from preclinical tests have led to its development in clinical phase I/II to test the tolerable dose and the quality of response.

 

A production platform
In addition to CAM-H2, Precirix has identified multiple targets (various receptors, several entry points), different isotopes (radioactive loads) and also a series of applications.

 

The next phases
To carry out the development phases on several products, Precirix managed in 2017 to complete one of the largest series A fundraisings in Belgium, raising EUR 30 million. A new round of funding is in preparation to continue Phase II clinical development as well as the development of promising new Trojan Llamas.