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Carlos Buesa

CEO and co-founder of Oryzon Genomics

Carlos Buesa is the CEO of Oryzon Genomics, a clinical biotechnology company he founded in 2000 along with Tamara Maes. Oryzon Genomics, leader in Europe in epigenetics, has signed the largest agreement between a Catalan biotech firm and a multinational pharmaceutical corporation, Swiss-based Roche. 

The agreement between Oryzon Genomics and Roche, a company specializing in developing oncology drugs, encompasses researching, developing and marketing inhibitors of LSD1 for oncology, hematology and other diseases. When these inhibitors (such as ORY-1001) reach the market they may be able to cure Acute Myeloid Leukemia (AML).

Tell us about the agreement between Oryzon and Roche.

It was a top-notch international agreement, not only financially but also in terms of its implications for research. It is the result of many years of work and a lot of effort, and recognition of the capabilities of the whole team, which has taken risks and persevered despite economic difficulties. Biotechnology isn’t a field for the faint of heart: you have to persevere and take risks and this is what we’ve done, we’ve been daring and we’ve done frontier science. Innovative science is key if we want to move forward.

And in the end, you’ve been rewarded.

Oryzon Genomics began working on LSD1 in 2008, when it was still relatively unknown and no one had any idea what it could be used for. And thanks to this risk, now we’ve reached a top-notch agreement. In addition to the upfront payment of $21 millions, there will be nearly $600 millions more in development and sales milestones, as well as royalties that, once Roche begins marketing the drug, could mean several hundreds of millions of dollars each year for the company. And the agreement also includes Roche providing at least one million dollars per year for internal Oryzon research.

What makes ORY-1001 so special that it has attracted the attention of a multinational corporation like Roche?

The real possibility of killing leukemia stem cells that would prevent relapses and, thus, make it a definitive cure for those suffering from acute myeloid leukemia (AML). The ORY-1001 molecule, which has received orphan drug designation, inhibits LSD1, an enzyme that eliminates signals in histone and leads to changes in the chromosome reading context while deactivating the gene. This small chemical variation is enough for histones, which are the scaffolding around which DNA coils, go from an active to a passive shape. We know that leukemia stem cells need LSD1 activity to maintain the cancerous oncology program. By blocking this activity, which is what leads to relapses, we can eliminate this cancer.

Moreover, our molecule is a covalent inhibitor that attaches permanently to the protein. And as it is hugely active, only a very small quantity is needed. This means that it has very few side effects. It’s a very, very clean drug, pharmacologically speaking. This is one of the characteristics of our molecule that most interested the pharmaceutical industry.

Does the drug only work for AML?

We know that our mechanism of action works really well on a subtype of acute myeloid leukemia and apparently on a subtype of acute lymphoblastic leukemia as well. It may work on more than one type of leukemia, but we don’t know yet. We also know, because there are reports in scientific literature, that there are some types of lung, breast and brain cancer on which this mechanism of action could be effective. This is one of the issues we will develop over the coming two or three years in our research in collaboration with the Roche Transnational Clinical Research Center.

Is epigenetics the future?

It’s not that it’s the future… In science, like in life, there are trends. But epigenetics has opened our eyes to something truly spectacular: the information that makes our bodies work has different levels of regulation. Until recently we believed it was the information in chromosomes, but now we know that there is an additional regulatory element, and that there can be different functionings of the genome without any mutation. How living beings are regulated and the difference between health and disease is highly complex and epigenetics is giving us a new view of it, allowing us to get a much more detailed look at diseases and fine-tune personalized therapies.

In fact, your drug also falls under the category of personalized medicine.

That is part of our current strategy, to do personalized medicine. It’s very difficult to find a molecule that works for all cancers. It’s easier to find one that could work for specific subtypes of cancers where the spectacular therapeutic effect overwhelmingly compensates for the risks and side effects patients suffer.

Have you seen any return on this agreement yet? Have any other international companies contacted you?

There has been some movement. There are several stakeholders interested in Oryzon, both from the financial and industrial arenas, in Europe and the United States. Oryzon was already considered a world leader in epigenetics in the United States, and this agreement has only multiplied our recognition on the cutting edge of this field around the world. And that, obviously, attracts the interest of investors, venture capitalists, international stock exchanges… Now we have a great showcase.

Any offers you would seriously consider?

No, for now the company is drawing up a strategic growth and internationalization plan for the coming four years. We’re beginning a new era and we can’t just sit here enjoying the sweet moment. We have to ride this wave and let it take us even further. The coming months will be really exciting. We’ll be at the most important international events in Europe and the United States, and we already have numerous interviews set up.

But have any of these offers been to develop other drugs from your patents?

We’d have to think about that. The agreement with Roche is very interesting in that it is restricted to two Oryzon patents. So we’re totally free to develop or reach any agreements we wish for the other 16 patents. Right now we’re working on a neurodegeneration program on another inhibitor we’ve obtained spectacular results with in Alzheimer mice. We’ve shown that chronic oral treatment with our compound radically slows cognitive degradation, memory loss. This, in some way, consolidates our hypothesis: our drug would be able to stop Alzheimer.

Isn’t that a bit optimistic? Risky?

Of course it is. But if we can confirm this finding in humans, it would be a turning point. However, it has to be said that animal models always have a certain percentage of uncertainty when transferring to humans, and even more when dealing with neurodegenerative diseases. We’re forced, therefore, to be as prudent as possible. But despite this caution, the results we’ve seen so far in animals have been spectacular.

So your top goal is to reach an agreement with a pharmaceutical company to develop the drug?

Possibly. Or we could also opt to raise funds to do proof of concept ourselves.

You already had in mind that you wanted to open a subsidiary in the United States. Has this accelerated that idea?

It’s true, for a couple of years now we’ve been considering opening a subsidiary but we hadn’t done so because of the difficult economic situation. We wanted to focus on advancing the anti-leukemia molecule as much as possible. But now it is one of the company’s top priorities, and we’re pretty sure we’ll have an office in the United States before the year is out.

A subsidiary, research at the Roche laboratories... will that pull the company towards the United States?

No, no way. We are committed to continuing to do our research in Cornellà. Here in Catalonia we have well-trained human capital, not just good scientists but people who know how to manage science, manage companies, who know the biotechnology and business sectors. We’ve improved enormously. What we need now is the infrastructure to grow companies and stable policies that foster innovation and high-technology companies, not just biotechnology.

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