Name: Boro Dropulic
Position: Founder, CEO, Lentigen
Background: Founder, CSO, Virxsys 1999 2004
Education: MBA, Johns Hopkins University 2004
PhD, pathology, University of Western Australia 1988
BS, microbiology/pathology, University of Western Australia 1983
As founder and former CSO of Virxsys, which is using lentiviral vectors to develop therapeutics, Boro Dropulic's founding last year of Lentigen was a natural next step. His new company, which is headquartered in Baltimore, is focused on commercializing lentiviral vectors for research and therapeutic applications, while also building up an internal drug-development program.
This week, Dropulic spoke to RNAi News about Lentigen and how the nine-person company hopes to penetrate the RNAi market.
Could you start with some background on the founding of the company?
This company was started in late 2004, and we were capitalized in April 2005. Basically, it's leveraging lentiviral vector technology for all of its applications, both therapeutic and for research. Our core competency as a company is really lentiviral vector manufacturing. … We can produce vectors at the small scale, at the research scale. Also, we are developing a GMP capability for the production of these vectors at the clinical scale.
For research, the researcher can come to our website and, using a web-design tool that is called LentiDesign, they can custom create their own lentiviral vector that can either contain a gene or an RNAi [molecule] of interest. We will manufacture that vector for them within about 60 days and ship it to them. The advantage of lentiviral vectors is that you can transduce your target cells at high copy numbers, so you can get multiple copies of, say, your lentiviral vector that expresses an RNAi [molecule]. That gives you a much better chance to express your RNAi to higher levels within the cell, giving you a better chance to knock down your target gene. … A researcher can basically come into our website and basically type in their specific RNAi sequence into the promoter regions of our vectors. Those promoter regions, which are the typical ones that are out there, will express the RNAi within a cell. …
On the therapeutic arm, we are developing the company as a contract lentiviral vector manufacturer that can produce clinical-grade vectors that either want to express a gene or an antisense or whatever they want to express to be used in clinical trials. We also have our own internal program that we are developing; we're collaborating with both government and academic groups to develop some products for clinical trials.
In terms of clinical manufacturing, what's the timeframe for when you'll be scaled up?
Q2 of 2006.
Your lentiviral vector technology, could you describe it? Are there aspects that differentiate it?
From other vectors? Yeah. Vectors that are used out there for research are plasmids. A researcher will clone their RNAi [molecule] into a plasmid, and then use a lipid reagent or a calcium phosphate to transfect their cells. Generally, they can get 60, 70, 80, 90 percent transduction efficiency with these lipid reagents. But that's only temporary it only lasts for a few days, and then because the gene is not integrated into the chromosome, when those cells divide, the gene is lost. So you only have a very narrow window in which to analyze for the effects of your RNAi [molecule]. On the other hand, our lentiviral vector … allows you to insert an RNAi [molecule], for instance, or a gene or antisense [agent], into the vector. Then, when you add the lentiviral vector to the cell, the vector integrates into the chromosome and you get stable, long-term gene inhibition.
In regards to using these vectors therapeutically … have you done any proof-of-concept work?
We haven't specifically, but there is in the literature out there use of lentiviral vectors incorporating RNAi to inhibit transgenes.
There's been a lot of press regarding the use of lentiviral vectors in humans and safety [issues]. What are your thoughts on where that stands now?
I was the sponsor-investigator on the first lentiviral vector trial that was just recently completed at the University of Pennsylvania, so I'm very familiar with all that. I think you'll find that lentiviral vectors will prove to be safer than any other integrating vector system that's out there.
There are a couple of reasons I believe that. One, this lentiviral vector is derived from HIV. If you look at the 40 million or so people infected with HIV worldwide, with many integration events and many defective viruses that are produced during the lifecycle of the virus, there's not a single documented case linking HIV to a T-cell leukemia. So I think you'll find these lentiviral vectors prove to be a very safe vector system to gene delivery in humans. They have to be constructed the right way, but when they are … with the appropriate safety features, they will be a very safe system to use for therapeutic purposes.
How's the company approaching the therapeutic side of things? Are you looking for a partner that you'll work exclusively with in an indication or application, or will you broadly out-license the technology to whoever is looking to use it?
A bit of both I think is the correct answer. At the moment, we're collaborating with many academic institutions to move certain therapeutic indications into the clinic. We're also willing to collaborate with companies with their own therapeutic payload, and work with them to help them develop their products. So we're willing to both license our product out to companies for their own specific uses, and we'll also have our own indications that we will develop.
Are any of the ongoing collaborations RNAi-specific?
Not at this point. But there are some coming down the pike that will be. We are in the middle of discussing this with one or two groups. But nothing has been consolidated as of yet.
Are those both academic [groups] you are talking with?
What about the internal programs?
We're willing to develop therapies to a certain stage then license them out. It's probably better that I don't talk about what these indications are at this time because they're early in development. It probably would be premature.
Is RNAi something that you're looking at for internal work?
Absolutely. RNAi is a very broad platform technology, and lentiviral vectors can really enable RNAi to be used in many disease settings. There are several targets that we're already thinking about.
And those are undisclosed at this point?
We can disclose hepatitis C.
Just a couple of housekeeping items. You said you were capitalized in 2005.
Greenwich Biotech Ventures is the lead investor.
Can you comment on pricing [for your vectors for research]?
Let's say a researcher wants to express an antisense or an RNAi [molecule]. For the first vial of material, we will do all the cloning, the manufacturing, the quality-control testing, and ship it out for $1,995. Then, because the cloning has been done, additional vials will cost $500.
Is pricing the same for academic and commercial researchers?
At the moment, it is.