BIO 2011 biotech profile: Patrys

One of the costs of being a complex organism like us is that occasionally the odd cell misfires for some reason and either divides in abnormal ways or refuses to expire according to the protocols of programmed cell death. The result can be a precancerous cell, and at any one time we may have millions dwelling in our bodies.

But there’s no cause for alarm. Our bodies are equipped with a sophisticated tiered defence system that actively hunts down abnormal and precancerous cells, singling them out for elimination. As a result, the vast majority of these wayward cells never have the opportunity to develop to become a tumour.

In fact, it’s only in those rare occurrences when one does slip through the defences that we must resort to more extreme measures, such as chemotherapy. Yet often the treatment for cancer is a mixed blessing.

Lacking the nuance of our immune system, these treatments often catch a swathe of healthy cells in the crossfire, leading to the all-too familiar side effects of many anti-cancer drugs.

But what if we could co-opt our immune system and amplify it in a targeted way to give it a boost when it comes to tackling cancer cells? What if we could isolate the antibodies that zero in on the proteins that uniquely appear on the surface of cancer cells and have the body’s natural defences take the task of eliminating the cells from there?

That was the seed of an idea that inspired Dan Devine to establish Patrys using research that originated from Columbia University in the United States and coupling it with the technology of the German biotech OncoMab.

It was a radical approach at the time with some substantial hurdles to overcome before the principle could be applied in practice, but the potential of antibody therapies attracted quite a bit of attention.

One of those who watched with interest for some time, ultimately joining Patrys in August last year, is Marie Roskrow, who was first the Chief Medical Officer and President, and is now CEO of the aspiring biotech.

Roskrow is trained as a haematologist and oncologist, and has worked in Europe and the US in leukaemia research, transplantation, and spent time at the University of Munich as professor of T cell immunology.

---PB---

Following her academic stint, she moved to the investment bank Lazard, advising biotechs on business development. It was during this time she started consulting for Patrys and became increasingly intrigued by the technology.

“My attraction grew over time, and that’s ultimately why I ended up joining Patrys full time,” she says. “Patrys is an oncology company, which is my interest, and it was early stage with novel technology, which I’ve always been attracted to rather than me-too technologies. Antibodies, T cells and dendritic cells were also historically what I’ve worked with. I understood the technology.”

Yet there’s always a risk involved with pursuing novel technology, and the risk with Patrys was whether it could move its antibody technology from the lab to the clinic, which would require overcoming some considerable manufacturing issues.

The kinds of antibodies Patrys is interested in – immunoglobin Ms (IgM) – don’t lend themselves to bulk manufacture. But after a lot of hard work, Devine was able to bound those hurdles and developed technology to manufacture the antibodies in quantities required for clinical or commercial use.

According to Roskrow, this was the turning point that made Patrys such an attractive proposition. Not only could Patrys manufacture the antibodies, but it had a cadre of lead candidates that targeted a wide range of cancers, plus a slew of other contenders in its pipeline.

Lifting Roskrow’s confidence even further was that in recent years more and more companies have jumped on the natural antibody bandwagon, effectively lending endorsement to the technology and raising the credibility of Patrys in the process.

Power from within

According to Roskrow, one of the strengths of Patrys’ technology is that the antibodies are entirely naturally occurring. “They’re not manufactured, they’re not changed in any way,”she says.“They are the natural antibody that we’ve found in cancer patients.”

However, where the body produces thousands of antibodies in varying degrees of abundance and effectiveness, Patrys can lend a hand to the natural process and isolate only those antibodies that singularly target proteins only found on cancer cells and not on any healthy tissue.

“We’re only interested in antibodies that are highly specific for cancer. One of the key advantages of these antibodies is thatthey don’t bind any normal tissue whatsoever. Theyonly target the tumour cells.”

---PB---

This is in contrast with many existing antibody therapies, where the antibodies are either manufactured artificially or derived from animals, so they’re not as precisely targeted as those developed by Patrys.

“Many of the current antibodies are specific to a certain degree, but they also target normal tissue, so they cause side effects accordingly. Because we’ve shown in many types of cancer that our antibodies only bind to the tumour, we don’t expect to see any side effects as a result of treating patients with our technology.”

The process starts by identifying just the right antibodies that have these precise binding characteristics. This is where the immunohistochemistry expertise of the Patrys research team comes in, enabling Patrys to screen out antibodies that bind to any normal tissue.

They then use flow cytometry to identify the antibodies that bind to the surface of the tumour cell, drawing on their library of thousands of tumour samples. A secondary screen is then run using functional assays to see what the antibodies are binding to and how they kill the cancer cells.

The end result is a rigorous process designed to filter out any antibodies that target anything other than cancer cells, and leave only the most effective antibodies, each of which has a completely different target, and which can potentially be taken on to the clinic.

The next step is manufacturing, and many people had doubts that Patrys would be able to produce the quantities of antibodies required for clinical use. “A lot of people had theoretical issues with large-scale manufacturing of IgMs,” says Roskrow.

“They’re big, polymeric, heavily glycosylated antibodies, and producing these things will be a problem. And sure, we had that problem. For years on end we had that problem.

“But as time progressed we overcame the manufacturing difficulties, and now we can produce these in sufficiently high quantities for use in clinical trials. We can produce them as well as Roche and Genentech can produce IgGs [immunoglobulin Gs].”

Read part II of BIO 2011 biotech profile: Patrys, from theory to practice.