Roche China R&D Center Chief Scientific Officer Li Chen On Being a Pioneer in China: An Interview With PharmAsia News (Part 2 of 2)

Swiss-headquartered Roche was the first multinational pharmaceutical outfit to establish a research and development center in China, and the company recently set up one of its P harma P artnering groups in Shanghai. Roche's China CSO Li Chen sat down with PharmAsia News to talk about how the company is approaching R&D in the region and evolving in tandem with the pharma landscape in China. Chen is also a member of the networking organization BayHelix, which links Chinese life sciences executives.

[Editor's note: This is part two of a two-part feature. (Also see "Roche China R&D Center Chief Scientific Officer Li Chen On Being a Pioneer in China: An Interview With PharmAsia News (Part 1 of 2)" - Scrip, 25 Aug, 2009.) discussed the beginnings of Roche's R&D Center in China and what influenced the MNC to move in that new direction. In part two, Chen discusses how Roche is approaching R&D differently in China and the role that China will play in the global pharmaceutical arena.]

PharmAsia News: How is Roche's R&D program in China different than Roche's R&D program in the rest of the world?

Li Chen: I think we take a project team-based approach and the focus is on the target expertise and the biology that we can establish and have an in-depth understanding on that. This understanding can come from our own experts in-house or from a partner from biotech or from local universities and institutes.

PharmAsia News: Are you looking for a Chinese biotech outfit to acquire?

Chen: I think Roche always brings in the innovation that can add value. For instance, we acquired a company called Arius in Toronto doing high-speed antibody screening and differentiation platforms. We also acquired a company from Alnylam doing siRNA technology, and we have a small biotech company called GlycArt working on second-generation antibodies, glycosal antibodies.

And then recently we partnered with another company that is doing RNAi delivery .

PharmAsia News: And, delivery is the holy grail in RNAi technology, right?

Chen: Right, because you are there doing the [conjugation], multiplication and delivery. So those are the things we are looking for. We are not looking for acquisitions for the heck of acquisitions. We'll bring in those companies that we feel have a common interest, an expertise that we don't have or couldn't match.

PharmAsia News: Roche's biotech acquisitions have been quite unique in that the acquired companies have remained intact, such as Genentech and Chugai. What types of challenges would such an acquisition in China bring, keeping those corporate cultures intact?

Chen: Well, if you think about that as difficult, actually it's not. We want to create a culture in Shanghai at RRDCC that's very different from the Roche culture. We will operate more like a biotech with focus and science-driven decision making, and we benefit from Roche global R&D knowledge and expertise. Just as with Genentech, where the Genentech Research and Early Development Center will stay intact so that they'll keep their drug discovery research and the culture of drug discovery intact, that center is going to report directly to the CEO of the company, not part of the Roche global R&D organization.

[Editor's note: Roche's Global Licensing Director Stella Xu, spoke with PharmAsia News' Shanghai bureau about Roche's partnerships in Asia ( (Also see "Roche Global Licensing Director Stella Xu and Business Development Director Frank Grams On Seeking More Innovation In China And Korea: An Interview With PharmAsia News (Part 2 of 2)" - Scrip, 12 Mar, 2009.) .)]

PharmAsia News: So you take a hands-off approach until the critical proof-of-concept point, is that it?

Chen: Right. And say, Shanghai finds something that is more of a niche market. Roche Global might tell us that the project is not quite [big enough] for this global, massive engine to run this particular project, and then the opportunity for Shanghai would be to work with the local CROs or biotech and still realize the value.

PharmAsia News: Will you be bringing some of your Genentech employees here to China?

Chen: No, I don't think it's the intent to mix the scientists. I think that the traditional concept is you take over, you integrate, and you put your so-called "thumbprint" on the new organization. We try not to do that here. But it's a tendency.

We try to find a different way of doing things. And it's often a challenge, but this is the challenge we sought.

PharmAsia News: It seems more companies are doing less research and more drug development. Do you see less "R" and more "D"? Is part of that a budget constraint, do you think, to stop feeding the pipeline machine and to try to get out first what is already in the pipeline?

Chen: It's two parts. One is how you define "R." In the past, I think the "R" was defined by running the process, where you basically set up the assay against a target. And then you run through millions of compounds, and come out with a hit, a chemical starting point. Then you put a bunch of chemists on there and make all the possible variations, test them and then figure out which one might work in the animal model, which you may or may not believe in, but that gives you a sign that makes you think it might work. And then you pick those things and run them through the toxic model and you see which comes out from there. If it is safe you put it into clinical trials. Right? You're making cars.

At each step, you find those things that disqualify something, and then you do an attrition, and hopefully at the end, the good one is left over, which is not always the case. This process-driven attrition model does not work and that is why our productivity is very low: 2-3 percent for the whole pharma and biotech industry.

PharmAsia News: And now you're not doing the same thing?

Chen: No, not at all. You know, there is a different way to do it, but the concept is not the same. In the attrition model, the concept is that the more dice you roll, the better chance I'm going to have. But I always say, "You're rolling the wrong dice! You don't get anywhere if you just roll the dice at the poker table!" That's where the disconnect is. There's the disease biology and understanding the fundamental process on a scientific level that will make a difference. And that discussion was not there when we made decisions on where to invest. With our scientists we're talking about the genes, the gene products, and then the disease, and how those three, the different layers, are interconnected. We need to know how drugs are going to impact them on all three levels, and what experiment we need to do to demonstrate that.

PharmAsia News: So, it's understanding the pathways first then, is that the biggest difference?

Chen: Right. We need to understand disease processes and pathways that lead to the disease, and the disease genesis. And you do not have a comment process of diseases since each disease could be different due to the genetics and epigenetics. If you follow the standard drug discovery process, you do not have a disease relevant assay in place for you to run through. You have to come up with the assay. You have to come up with the model, but first you have to understand the pathway and the mechanism, and then you make your assay disease relevant and pick the right molecule, rather than set up a high throughput-screening assay and focus on the numbers.

But all the new technology available allows us to do a better job and we just use it for different purposes. Remember how many genomic companies were formed during the genomic age? Not much came out of them, right? However, you can say that advances in molecular biology and genomic sciences have led to the boom of the biopharmaceutical industry and RNAi technology that may shape our future of drug discovery. With the development of the quantitative, real-time PCR technology and biochip technology we can use them to help select our patients with biomarkers. We can use those tools to do more relevant studies, rather than just running the pipe.

I always like to understand the link between the biology and chemistry, and how we use small molecules and big molecules to tackle, from a structure biology point of view, looking to the function of the cells and looking at the biostructure linked to the cell functions to cure diseases.

Ten years ago, when we talked about structural biology, it really wasn't structural biology. We were really talking about biostructure. We saw crystal structures of proteins and receptors for the purpose of drug design. You have your target protein there and then you can dock your small molecule in. You can do the modeling based on that. Now, we're working together with top-notch academic labs on structural biology at Tsinghua University, using the structure to understand the biology process and the mechanism, and at the same time, figure out a way to design drugs.

And that's very different. Conceptually, that's very different - this is the evolution of the concepts in drug discovery, and we in Shanghai are testing them.

- Tamra Sami ([email protected])

[Editor's note: Want to know more about growing your pipeline in Asia? Don't miss the PharmAsia Summit Oct. 26-28 in San Francisco where Li Chen will participate in a China R&D roundtable discussion with other pharma leaders in China. Click here for more information.]