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Else Marit Inderberg and Sébastien Wälchli often work in one of the cell labs in Oslo Cancer Cluster Incubator. Photo: Christopher Olssøn

How Cancer Research Becomes a Company

The Department of Cellular Therapy is great at transforming cancer research into new companies. The latest spin-out is Zelluna.

 

The Department of Cellular Therapy at the Radium Hospital, Oslo University Hospital, features one of Europe’s largest and most modern good manufacturing practice (GMP) facilities for cellular products. Head of the department is Prof. Gunnar Kvalheim. They are also conducting translational research, and their research has been spun out as several companies, such as the newly established company Zelluna.

The immunomonitoring unit is a major part of the department, and is led by Else Marit Inderberg. This unit is situated in the Oslo Cancer Cluster Incubator, which is an integrated part of the Oslo Cancer Cluster Innovation Park. A translational research lab has been created and is associated to the immunomonitoring unit.

The cancer killer
“Our major strength is that we have all aspects within the department to take cellular research from the bed to bench and back again. We have the equipment and the specialists to do everything here”, says Inderberg.

Together with Sébastien Wälchli, she is also the project leader for the translational research lab. Here, they develop cancer vaccines and work with adoptive T cell therapy. A T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated immunity. T cells have the capacity to kill cancer cells.

In the lab, they look for a T cell receptor (TCR), which is a molecule found on the surface of T cells. They use Chimeric antigen receptors (CARs), which are engineered receptors that graft an arbitrary speci city onto a T cell. Ultimately, the researchers work with a universal cell line for cellular therapy – a universal cancer killer.

This is a T cell, or more precisely, an actin cytoskeleton of a T lymphocyte. The picture is obtained by a special micro- scope. The cell’s size: 38*38 μm. Photo: Pierre Dillard

Innovation from the biobank
“In the translational research lab, we think innovation all the time. In our research, we actively search for solutions to unmet medical needs within cancer”, says Inderberg.

The translational research lab was built upon the work done by the section for immunotherapy established by professor emeritus Gustav Gaudernack, and most of its activity relies on the use of a database of patient samples called the biobank. This specific biobank represents an inestimable source of information about the patients’ response to immunological treatments over the years. Furthermore, the patient material can be reanalysed and therapeutic molecules isolated. This is the basis of the company Zelluna.

Industrial collaborations
The Department of Cellular Therapy is heavily involved in both academic and industrial collaborations. The latter include collaborations with several biotech companies as well as pharma companies situated in the Oslo Cancer Cluster Innovation Park, developing novel immunotherapy cancer treatments. Examples of industrial collaborations are the German company Medigene, the Norwegian biotechs Targovax, Ultimovacs, Lytix and PCI Biotech, and the bigger biopharmaceutical companies BMS, Novartis and ThermoFisher.

In addition to their industrial collaborations, the Department of Cellular Therapy also wants to commercialise their own projects.

The Zelluna Spin-out
“Our latest spin-out is Zelluna, which has recently been set up as a start-up. Staff has just been hired to drive the development of TCR-based therapies to clinical trials”, says Sébastien Wälchli.

The TCR-approach is based on identication of T cell receptors from patients clinically benefitting from treatment with vaccines from back in the nineties and early 2000s. The approach is to modify the patient T cells to express the same receptors before giving the cells back to the patients, ready to combat the cancer cells.

The company has been established through the efforts of the Radium Hospital Research Foundation as well as Inven2.

“This is a very interesting and unique approach. We are eagerly anticipating the development of the company”, says Inderberg.

Targovax in phase IIa with cancer vaccine

Immunotherapy specialist Targovax reaches Phase IIa in operable pancreatic cancer with its TG01 immunotherapy. RAS specific immune responses were induced in all 6 patients in Phase I, and no substantial side effects were observed in the patients. The clinical trial has now expanded from Norway to two sites in the UK.

 

Oslo Cancer Cluster member Targovax started in 2010 to develop targeted immunotherapy in the form of therapeutic cancer vaccines. The TG01 vaccine has been given as treatment to cancer patients, in combination with chemotherapy after surgery, to prevent relapse. TG01 is granted Orphan Drug Status for pancreatic cancer in both EU and USA. The promising Phase I results has triggered a $2M (12.5 MNOK) milestone from current owners.

 

Clinical trial in phase II
Gustav Gaudernack, professor emeritus at Oslo University Hospital, and one of the inventors of the technology, states: “I have great expectations for the principle of treating patients with peptide based immunotherapy, which educates the patients’ immune system to fight cancer. It is exciting that the TG01 project now reaches this important milestone in combination with chemotherapy”.

The clinical trial has now formally entered Phase IIa, and the trial is expanding from Norway to two sites in UK, namely The Christie NHS Foundation Trust in Manchester, and The Clatterbridge Cancer Centre NHS Foundation Trust in Liverpool.

UK Principal Investigator Professor Daniel Palmer says: “Vaccination targeting RAS mutations is an extremely promising area of research and with our considerable experience in conducting multicentre immunotherapy trials, we are looking forward to help expand Targovax’s TG01 trial into Phase IIa.”

Important milestone
CEO Hanne Mette Kristensen commented: “Through this important milestone, we have significantly reduced risk in TG01 development by confirming observations of specific immune response and safety for the patients. This is very encouraging. We will continue to work towards confirming the link between TG01 treatment and effect on survival for these patients. We are proud that the two UK sites now participate in the clinical trial – we see this as a quality mark. ”

Targovax’ RAS specific immunotherapy triggers both cytotoxic- and helper T-cell- immune responses, educating the patients’ immune system to recognize and kill the cancer cells.

New IPR is established as a basis for expanding pipeline to broader indications.

“Based on these results, Targovax is now focused on completing the ongoing Phase IIa study with TG01 in surgically resected cancer. In addition, the company is initiating preparations for a randomized Phase II, and completing a Phase I trial with TG02 in larger indications such as colorectal cancer and non-small cell lung cancer (NSCLC),” concludes Kristensen.

Read more in the press release on Targovax’ website.

 

About Targovax
Targovax develops immunotherapy in the form of therapeutic cancer vaccines. TG01 is being developed for pancreatic cancer as its first indication. The drug has been investigated in exploratory trials in patients with promising results. The company is located in Lysaker, close to Oslo, Norway.

TG01 and RAS
TG01 is a therapeutic cancer vaccine which means that it educates the body’s immune system to recognize and kill the cancer cells. TG01 is based on pioneering research into RAS mutations in the Norwegian Radium Hospital (now Oslo University Hospital) and Norsk Hydro. Mutation of RAS disrupts normal cell division signaling and contributes to development of cancer cells and tumors. RAS mutations are found in approximately 25% of all cancers and in particular in pancreatic cancer (80-90%), colorectal cancer (40%) and non-small cell lung cancers (30%). Lead candidateTG01 has Orphan Drug status for pancreatic cancer in the EU and US and is currently in Phase IIa trials in surgically resected pancreatic cancer, patients start treatment 1-8 weeks after surgery.

Pancreas cancer and other RAS-mutated cancer forms
Pancreatic cancer is a disease affecting 116 000 patients each year in EU and USA, and approximately 690 persons each year in Norway. Approx 15-20% of these are discovered at an early stage and are operable. The mortality is high, and the prognosis for these patients has been more or less unchanged the last 30 years. Approximately 80-90% of patients with pancreatic cancer have RAS mutations in the cancer cells.
RAS mutations are also frequent in colorectal cancer, non-small cell lung cancer and other cancers. Patients with RAS mutations within these indications have proved to be difficult to treat with current treatments, and there is a significant unmet medical need.

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5 Oslo Cancer Cluster SMEs granted BIA-funding

The Norwegian Research Council recently granted BerGenBio, PCI Biotech, Lytix Biopharma, Oncoinvent and Ultimovacs –  all Oslo Cancer Cluster member companies – funding  through the Programme for User-Driven Research Based Innovation (BIA).

In total, the Research Council will grant a record amount of 444 million to 58 Norwegian companies over four years, of which 10 are biotech companies – which is also a new record.

BerGenBio, Lytix Biopharma, PCI Biotech, Oncoinvent and Ultimovacs will receive around 10 million NOK each over 4 years, depending on the outcome of the contract negotiations between the council and the company. Funding from the  BIA programme is a quality stamp since the companies compete in “open class” where all sectors are represented. The funding may also in turn trigger interest  from private investors.

On the Research Council`s website you may find the total list of all the 58 companies (in Norwegian) and read more about the funding from the BIA-programme.