In 2009, three researchers from IDIBELL and ICO, Gabriel Capellà, Ramon Alemany and Manel Cascalló, launched a business initiative to develop a cancer therapy based on adenovirus. Thus, VCN Biosciences, which is currently located in Biopol'H and it was the first spin-off from the Bellvitge Campus. A few weeks ago, the multinational Grifols announced the acquisition of 40% stake in VCN. Manel Cascalló, CEO of this spin-off, is satisfied with the operation which will ensure the viability of the company.
What means the entry of Grifols into VCN?
Basically, the entry of Grifols is allowing the viability of the business and scientific project of VCN Biosciences. The entrance of Grifols, which is not a purchase but a capital entry, is a long-term agreement that allows us to release the work of seeking new capital for the company's viability. And also, we can focus on current projects.
Was it a surprise?
No. An agreement of this magnitude is never a surprise. VCN has been in contact with Grifols for over a year and half, and the contract, we have been talking for six months, with complex negotiations. It was not a surprise, but a joy.
How will this inclusion affect on the VCN projects?
Grifols participates in VCN because they believe in the projects we are currently developing. Therefore, the plan is technically and scientifically the same. The entry of Grifols will not change it. There is a very advanced candidate, the VCN-01, which is in clinical development and they are just investing in the company because they believe in the approach we have proposed. And they go for the second candidate, VCN-02, which is in an earlier stage. As in the first phase Grifols has a forty percent of the company, the corporate control is still in the entrepreneurial team. There are changes at the organizational level like the creation of a director board and, in not too distant future, possibly around six months, we will move on Grifols headquarters in Sant Cugat del Vallès, to integrate us to the dynamics of the group.
What is the main benefit for Grifols in this operation?
They are buying a ticket for the future. Grifols is a company with a visionary perspective. The future of the company is in the introduction of new technologies, innovation and new applications of biotechnology. And they clearly bet, in a determined way, with a clear future. They see their participation in VCN as a long-term project.
When you think about Grifols, you think about plasma...
Exactly, but if you analyze the structure of the company you can see that they are very cutting-edge. They were the first and one of the few local Spanish pharmaceutical companies quoted in the stock market and invested in internationalization. Today is more an American company than Spanish: a very important percentage of its workers are from USA and more than seventy-five percent of its turnovers are Americans. In Spain, they only have the ten percent of its turnover. It is a pioneer in many things, including its commitment to the future. Currently its market is the blood, but maybe their future may be different.
Grifols announced that if the required results are achieved they will expand their participation in VCN in the future...
Yes. In fact, the agreement we have signed is not short-term agreement. It depends on the results. Grifols has an obligation to continue investing in our society. So what is expected is that Grifols goes making a gradual entry into VCN.
What do you expect with the relocation of VCN into the Grifols headquarters? More space?
We will have more space, but this is not the point. VCN works outsourcing their services, both in manufacturing their products as well as in the clinical and preclinical research that we commissioned to the IDIBELL, for example. We only need an office space, but we don’t move to their facilities in order to win more laboratory space, in the first instance. At this moment, there is not an idea to produce the virus there, which is currently been done in Portugal. Perhaps it would be feasible in the future, but is an issue that the company must decide according to the results. Now it is not clear.
You said that you outsource many activities...
Yes, the production of the virus, our product, is done in Portugal, the regulatory counselling takes place in Barcelona, the intellectual advice is done in Canada, the regulatory toxicology is done in the Netherlands... The world of biotechnology is necessarily global.
The most advanced project is the VCN-01 virus against pancreatic cancer. How works this virus?
VCN-01 is a genetically modified virus developed to selectively recognize tumour cells and differentiate them from normal. It is an oncolytic virus. When it infects a normal cell, the virus is completely inactive but when the cell is a tumour, the virus recognized as such and it behaves like virus itself: it replicates in the cell. And it acts in two ways. On the one hand, it kills the cell and in the other hand it generates many copies of itself to infect other cells. This process will be repeated if the rest of the cells are tumours. So, you have a small bomb. Although the virus initially does not have a great power of penetration, it finished auto amplifying itself. Furthermore, the VCN-01 expresses an enzyme (hyaluronidase) which is a degrader of tumour extracellular matrix, which has many effects. The extracellular matrix prevents the diffusion of chemicals inside, provoking chemo resistance. Due to the enzyme tumour matrix is weakened, the spread of virus is increased and chemotherapy treatment may act more efficiently. The virus acts as a sensitizer of chemotherapy.
Did you have many problems working with viruses?
Our research clearly presents many challenges, like any medicine for advanced therapies. But it is basically an opportunity. VCN's team is very experienced with this technology, with more than fifteen years. We have experts who have advised the European Medicines Agency in such therapies. It is not more difficult to work with this technology than with other drugs. The regulatory agencies are more opened to talk about advanced therapies. In this area things are not so rigid, which gives you a certain capacity for dialogue. The oncolytic viruses may sound like science fiction, but they are being used long ago. Its effects have been analyzed for over a century, and they have been clinically shown to be safe. The selectivity of the virus is the problem better solved. It is not a danger to public safety. We are working to increase its effectiveness.
Why you have selected the pancreatic cancer?
It is a first choice, but it will be tested with patients with other kind of tumours. We have an orphan drug designation by the European Medicines Agency for pancreatic cancer, but that does not mean we can’t use the same virus for the treatment of other cancers. Why pancreatic cancer? Because it is a highly chemo resistant tumour, it expresses a lot of extracellular matrix, and it has no current therapy. It is easier to introduce therapies within this therapeutic niche because there is nothing to treat it. Our preclinical drug has been highly effective proved in this cancer.
It is being tested in the preclinical phase. How goes this study?
We are at the end of the preclinical phase of our product in animals. Now we are reproducing the studies under good laboratory practice (GLP) that will join the dossier to be submitted to regulatory agencies in order to get the permission to develop the clinical phases. The idea is to ask for the permission next January to begin the clinical trials at the beginning of the second quarter of 2013. The tests will be made with patients resistant to conventional treatment.
Where will take place these tests?
They will take place in Barcelona and Madrid, in the Catalan Institute of Oncology and in the Centro Integral Oncológico Clara Campal, respectively. They are two independent assays, one by intratumour administration and the other one by intravenous administration.
Apart from the VCN-01. Do you have other projects?
Indeed. A company like VCN must have different products. It is very risky to have only one. The strategy is to have a portfolio. We are working on a second candidate to have cancer indications, but not only. Conceptually, it is different from VCN-01.
What could VCN-01 be apart from pancreatic cancer cancers?
We believe that VCN-01 can run against cancer with a lot of extracellular matrix, but we have to validate it experimentally. Nowadays we do not know it. In the assays that will be indicated very soon it will be patients with different cancers. That will give us a first approximation of where the VCN-01 can run.
How many patients will participate in clinical trials?
Initially, there will be between 20 and 25 patients per trial, so between 40 and 50 patients in total. But we are thinking of doing some adaptive designs include more patients. This phase will last about two years, since a trial is longer than the other.
What evidence have you got in the preclinical stages?
In the two ways of administration we have therapeutic evidences. The type of patients in the two assays is different because it is not the same a locally advanced pancreatic cancer from a patient with metastases. In first case you have a local disease, and if you can control it locally, by intratumour therapy. Then it is been able to have an impact on patient survival. In case of metastases, we have to go through an intravenous because we need to get to the different tumours that are scattered.
What would be the next phase?
If it works, we move to a phase two. In phase one, we determine the toxicological profile, and it is not specifically designed to check how the product works, although we hope to obtain evidences. In phase two we will check the biological evidences, with a larger sample of patients from several hospitals.
If all works, when it could be applied in clinical practice?
It would not be before 2020. It is necessary the phase three, which is compared with the standard treatment. In a phase one or two your product is combined with conventional therapy, and therefore can’t have evidence. But in a phase three, after having demonstrated the biological evidence in phase two, you can see the power of your product or your medical approach.
What about the second candidate?
It is more risky to say. When we finish phase one of the VCN-01, we could begin to define the second candidate. But the phase one of the candidate VCN-02 would not arrive before 2015. It could overlap with phase two of the VCN-01, but is not sure.
As a product is surpassing the stages, the budget is growing. Does the entry of Grifols will bear all the costs?
Grifols ensures reaching the stage until 2017, ie, phases one and two of VCN-01, and probably phase one of the VCN-02, if it takes place. The contract guarantees at these points. But probably if the VCN-01 gives good results in phase two, I think in one way or another the product will come forward. However, the agreement signed today does not cover it. But we'll talk.
From a business standpoint, what is the horizon that you plan?
It is hard to say, because life takes many turns. We're talking about the future. You may end up with many candidates, or end up serving our leading candidate to treat many types of cancer or without results and we have to reinvent our product. Our company aspires to generate a portfolio of candidates, not huge, but enough apart to give us chance. This is our idea a priori. Our intention is to continue as a company for many years and help create a business network in the country, create jobs ... Starting a business has a strong social component; it is not only to create a candidate who can heal and save lives. | 
