The lipodystrophy project CGT2

The initial goal of CombiGene’s CGT2 project is to develop a gene therapy treatment for partial lipodystrophy, a very rare disease that today completely lacks adequate treatment. The project was licensed from Lipigon Pharmaceuticals AB in autumn 2019 and has expanded CombiGene’s operations to include metabolic diseases.

About lipodystrophy

The goal of the CGT2 project is to develop an effective gene therapy treatment for partial lipodystrophy, a rare disease characterized by altered fat distribution on the body. In the absence of normal body fat, various organs, primarily the liver, begin to accumulate fat, leading on to serious metabolic complications, including extreme insulin resistance, hypertriglyceridemia (elevated values of blood fat triglyceride) and liver steatosis (fatty liver). 

Selection of drug candidate

CombiGene is currently evaluating different drug candidates in several different efficacy studies with the goal of being able to choose a final candidate before the important concept verification study can start. A first selection of the drug candidates has been done in in vitro trials with liver cells and in an in vivo study where evaluation of which protein expression can be achieved in different organs has been carried out.

Several efficacy studies are now underway in vivo in different experimental animal models to measure the effect of the remaining candidates on the storage of fat in the liver.

PCT application

In August 2021, CombiGene submitted a so-called PCT application to protect the vectors developed within the CGT2 project. The Patent Cooperation Treaty (PCT) is an international agreement that allows companies to seek patent protection internationally for their innovations in about 150 countries. Within the framework of the PCT, a preliminary assessment of patentability is made before the application can proceed to the national phase where national patent applications are submitted. PCT applications are handled by the World Intellectual Property Organization (WIPO), a self-funding body within the United Nations. The in August submitted PCT application builds on the UK patent application filed last year and is a natural next step in ensuring adequate patent protection for the lipodystrophy project CGT2.

EUR 882,500 in project grants from Eurostars

In February 2021, the Lipodystrophy project was awarded EUR 882,500 in project grants by the EU’s Eurostars international funding program. Thanks to this funding CombiGene has been able to initiate a collaboration with the University Medical Center Hamburg-Eppendorf, which has a research group with experts in lipid research. The researchers at Hamburg-Eppendorf are involved in evaluating the different drug candidates CombiGene has in the pipeline and conducts several different preclinical efficacy studies. Through the Eurostars grant, CombiGene has also been able to strengthen its collaboration with Accelero, a German CRO company that will work on developing analytical methods to measure the efficacy of the CGT2 therapy.

CombiGene's project CGT2 is supported by the Eurostars Programme. Project ID: 114714

Collaboration partners

University of Michigan Medical School

CombiGene collaborates with Professor Ormond MacDougald at the University of Michigan Medical School. The collaboration comprises one pilot study and one main study in which CombiGene’s most promising gene therapy candidate within the lipodystrophy project CGT2 will be evaluated.

Stockholm University

In collaboration with professors Barbara Cannon and Jan Nedergaard at the Wenner-Gren Institute at Stockholm University, CombiGene has since spring 2020 been carrying out a project that aims to understand the mitochondrial functions and conditions of the liver, the organ at the center of the CGT2 project. The practical work is mainly carried out by Brazilian researcher Ruda Feitoza, who has a PhD on how the function of mitochondria can be affected by pharmaceuticals and nutrient uptake.

Lipigon

Lipigon is developing new treatments for patients with lipid-related diseases. The company’s foundation is based on 50 years of lipid research at Umeå University. The company’s primary focus is on orphan drugs and niche indications. At the end of October, the laboratory work at the Lipigon site in Umeå came to an end, just as planned in the agreement which was signed in 2019. CombiGene will continue the development of CGT2 with scientific support from Lipigon.

University Medical Center Hamburg-Eppendorf (UKE)

UKE is an important research facility and hospital in Hamburg. UKE researches in five main areas; neuroscience, oncology, cardiovascular research, health sciences research and immunology. Professor Jörg Heeren and his team have significant expertise in the target protein of CGT2, its function in the adipose tissue and its influence on lipid metabolism.

Accelero

Accelero Bioanalytics is a GLP certified laboratory specializing in delivering bioanalytical services for the drug development industry since 2011 and located in Berlin, Germany.

Milestones

2019

In-licensing of the project from Lipigon.

2020

Design of expression plasmids, which are a starting material for gene-therapeutic vectors CombiGene intends to develop for treatment of partial lipodystrophy.

In vitro studies (tests on liver cells) show proper protein expression.

Priority-based patent application filed with the UK Patent Office.

In vivo studies initiated for evaluation of the different gene therapy vectors.

2021

The lipodystrophy projects receive EUR 882,500 in development grants from the EU Eurostars program.

In August 2021, CombiGene submitted a so-called PCT application to protect the vectors developed within CGT2. 

The first in vivo study, a so-called expression study, shows that several drug candidates result in correct protein expression specifically in the liver, the organ that CombiGene intends to treat.

For the remaining drug candidates, efficacy studies are initiated in several experimental animal models.

2022

CombiGene signs agreement with Professor Ormond MacDougald at the University of Michigan Medical School to evaluate the leading gene therapy candidate within the lipodystrophy project CGT2.