With preclinical studies and a new licensing deal under its belt, immunotherapy drug developer PDS Biotechnology is getting its manufacturing plans in place and preparing to file an IND in next month or two so it can begin clinical trials of a therapeutic vaccine for HPV-related cancers.
In an interview with MedCity News, President and CEO Frank Bedu-Addo, who’s worked in drug development for companies including Cardinal Health, The Liposome Company and Schering-Plough, reflected on PDS’s move across state lines to secure early funding and explained some of the complexities of developing therapeutic vaccines for cancer.
The first time we reported on you was back in 2009 when you moved across the state line – from Ohio to Indiana – for $2 million in Indiana state grant funds. Can you talk about what went into making that decision?
FB: At the time we were very early stage and actively looking for funding. We had a couple of VC offers, but our board wasn’t too interested in those deals because of the dilution of equity. I think they wanted us to create more value before going for that funding, both for shareholders and employees, so we decided to look for alternative means. We’ve had significant support from NIH and were also looking to the state of Ohio and the state of Indiana. A VC firm that we were interested in introduced us to the Indiana Economic Development Corp., and compared to other states, Indiana’s funding program was very favorable to early-stage companies. The grant was significantly more than other states would offer – for example, it was a matter of $500,000 versus $2 million. Being in Ohio, we were very close to the border, so it wasn’t a very difficult decision to make – we would be able to relocate without losing any employees. Ivy Tech college was going to give us space with well-designed wet labs, and they were happy to work with us to get key things that weren’t already available. Putting all of those things together, it just made absolute sense to take that offer. It’s worked out very well. Operational costs in Indiana are quite favorable, and I would say we’ve had no regrets.
More recently, you signed a deal to license your technology to Merck KGaA for use in two of their experimental cancer treatments. What’s the significance of that deal to the company at this point?
FB: For an early-stage company with a novel technology, most people want to see clinical data before collaborating or licensing the technology. From our view, with this company that’s very well established in cancer vaccines and actually has products in phase 3, it was quite important in the validation of our technology. It tells the industry that this is something serious that you should pay attention to. Financial stability is very important, and being able to selectively license to a few companies while retaining value becomes a good way to validate the technology and raise some non-dilutive funds to continue our own internal drugs. We are in discussions with some other companies, both U.S.-based and foreign.
Can you tell me about the clinical trials you are preparing for?
Our first product, PDS 101, is to treat HPV-induced cancers. The first stage is CIN (cervical intraepithelial neoplasia) – that is the stage where lesions have begun to occur on the cervix but are not yet cancerous. In about 10 percent of women this will progress into full blown cancer. CIN-1 is typically not treated. Two and three are typically treated with surgery, but it’s not 100 percent effective, and usually when it comes back, it comes back with a vengeance.
The first human trial is going to evaluate safety of the vaccine in humans, first in the the CIN patient population. Safety trials are typically done with healthy patients, but the FDA was OK with us using this population. Because of this, we might be able to get some very early indications of what doses of the drug are working, which would help us going to phase 2, which is efficacy.
We already have two preventive HPV vaccines. How different is the approach to developing a therapeutic vaccine?
They are very different mechanisms of action. Think of the influenza vaccine – it contains an inactivated form of the virus. The immune system is tricked into thinking it’s seen the virus, so antibodies are produced and build up in the system. When the real virus appears, the antibody can rapidly neutralize it. Therapeutic vaccines involve a new set of immune cells known as T-cells. Many cancers display unique proteins not displayed by normal cells, and the immune system recognizes and responds to these abnormal proteins. People are trying to find out how we can advance response against these proteins. But cancers are smart – they have their mechanisms of invading with the way they grown and proliferate, so for these vaccines, it has to be able to effectively deliver that unique protein to the T-cells of the immune system and correct the protein, but it also has to be able to weaken the mechanisms by which the immune system is suppressed, allowing cancer to evade suppression. It’s a tricky thing.
What’s unique about PDS’s approach?
In pre-clinical studies, a single injection completely eradicated cancer, whereas typically with vaccines you have to give booster doses. We’ve done similar studies in human blood models, and one of our competitors in Europe has demonstrated very good human efficacy with a similar approach, so there is some indication that it’s likely to be effective in full-blown cancer patients.
The Versamune particles are taken up very effectively by immune cells. And one very important thing that we found is that Versamune particles are also very effective in reducing immune system suppression. When the mechanism by which cancer evades immune surveillance is weakened, T-cells are more able to seek out and kill cancer cells.
Another thing is that adjuvants are typically contained in vaccines as immune system activators. A huge problem is that the mechanism by which they influence the immune system has a toxic effect. This is one of the huge issues for regulatory agencies – only 2 adjuvants have been approved. Our vaccine has a completely different mechanism that does not induce any toxic inflammation.
What about all of the strains of HPV?
There are multiple strains of the virus; however it’s very well established that there are two key virulent strains: HPV-16, which is responsible for over 50 percent of cervical cancers, and HPV-18, which is responsible for another 20 percent. Our first vaccine is focused on HPV-16. When we go to head and neck cancer, there are some reports that HPV-16 may be responsible for up to 70 percent of those cases. It’s been more prevalent, so that’s what we are starting with HPV-16. Once we demonstrate efficacy, it’s very easy for us to add HPV-18, and there are some other strains as well.
Editor’s note: This interview has been shortened and edited for clarity.
[Photo from video at OneMedPlace]