A MedImmune SVP dishes on nanomed, antibiotic resistance, & his advice for biopharma
At the BIO 2015 conference last week, industry leaders from around the world converged in Philadelphia to discuss the newest developments in biotech and what lay ahead for the industry in the coming years. The excitement was palpable—not too surprising considering the vertiable boom that's been driving the sector in recent times.
One of the BIO panels, featuring Dr. Steve Projan, SVP of R&D and Infectious Diseases and the Vaccines Innovative Medicines Unit Head for MedImmune, an AstraZeneca subsidiary, focused on next-generation monoclonal antibody (mAb) technologies and antimicrobial resistance.
The crux of Projan's panel centered on identifying and engaging novel targets and antigens, considering that a staggering 60% of currently marketed mAbs target just seven out of thousands of antigens. Projan spoke to BioPharma Dive right after BIO to discuss his panel, the nuances of combating antibiotic resistance, his take on the future of targeted therapies—and even what biopharma execs get wrong these days.
Note: This interview has been edited for clarity and brevity.
The panel: Antigens and next-gen monoclonal antibodies
BIOPHARMA DIVE: Tell me a little bit about your panel discussion.
STEVE PROJAN: One of the top-line observations is that, in the biologic space, the large majority of drugs really only target 7 things out of the 5,000 potential targets that are probably out there. And I think one of the major foci of the discussion was not so much the antigenic targets that we're going after, but the evolution of the platforms for discovering the novel biologic drugs.
I think that there was a lot of engagement across the panel in new technology, such as making antibodies that can recognize multiple targets, multi-specific antibodies. We have one example at MedImmune that we can discuss. But in addition, using novel technologies that are not just producing classic monoclonal antibodies, but perhaps the single-chain antibodies that would be able to better penetrate the blood-brain barrier. I think it was probably even more focused on discovery platforms than on going after novel antigenic targets of which, I think we all agreed, there were certainly a wealth of potential antigens to target. The question is, how do we do it? I thought it was a very engaging discussion. This was kind of a "revenge of the nerds" group, without a doubt.
BD: So, the conversation was more about the platforms themselves. We'll get into that. But first, why don't we talk a little about what those specific targets might look like?
PROJAN: The intent of this particular panel was to focus somewhat on infectious disease. The sponsor for the infectious disease symposia was a competitor of ours, Novavax. We discussed, not in lot a of depth, but some depth, infectious disease targets.
As I always like to point out, the technology for using antibodies as anti-infectives doesn't date back to 20th century—it dates back to the 19th century, and was actually developed by Emil Adolf von Behring, the first Nobel laureate in physiology or medicine. He would raise immune antisera in horses against specific pathogens and then use the horse antisera as a therapeutic.
That was pretty much state of the art until the discovery of broad-spectrum antibiotics. That type of immune therapy is never really used much anymore. However, what was discussed was the fact that, since now we can make very potent monoclonal antibodies, and even engineer them to have very long half-lives, this technology is once again something that could be used without the downsides of getting serum sickness, since you're using horse protein instead of a fully human monocolonal antibody.
One of the great discussions in the session was about understanding the underlying biology. And what I like to point out in my particular presentation is, sometimes it's better not to understand the biology, but have a method in place whereby you can find somehting that has the right phenotypic properties and then figure out what it's targeting. I think one of the advantages in infectious diseases is that you have the luxury of being able to do that, whereas for human host targets, the purely empirical observation approach is going to be much more challenging, and you really do have to know what you're going after before you go after it.
The lesson there is, the biology's important. But on the other side of the coin, it's also important to have a really excellent assay that can inform you as to what the biology is. And that was a big part of our discussion on the panel.
Nanomedicine: The wave of the future?
BD: Let's take a step back and get out of the granular here for a bit—de-nerdify, if you will. Did you hear about one of these other panels at BIO, which featured folks including Neil Desai, a VP over at Celgene, about the promise of what they referred to as "nanomedicine" as sort of the next frontier of drug development? Desai used the example of Celgene's albumin-bound Abraxane, a prostate cancer drug, and said that applying that same sort of technology to monoclonal antibodies was the next big thing. He was talking about cancers, but what do you think about that?
PROJAN: Certainly many of us have been thinking in those terms, where the ultimate future for both oncology and infectious diseases—it's all a matter of finding the cells you want to get rid of. Be they infected with a virus, be they a bacterial cell, or be it a tumor cell, it all gets down to the same principle, which is removing those cells. Killing them, clearing them from the body. And how do we literally build machines that can do that? And I think a lot of the antibody discovery we're doing now specifically recognizing tumor-surface antigens for example, will put us in a position in the future of actually building those nanomachines that can purge the body of infectious organisms or tumors. It's the same general principle.
Right now, it sounds more science fiction than science. But we are actually now putting together the tools that will allow us to build those machines into the future. And I absolutely believe that's going to be the way to go.
Clearly, the more biomarkers we can detect, especially in a non-invasive way, will lead to earlier diagnosis, which we always know is key to dealing with disease. Understanding the biology, understanding what our antigenic targets are, the essence of our panel, will allow us to build those nanomachines into the future, which absolutely will be the way to go. It will eliminate the need for broad-spectrum drugs in the antibacterial space, because we'll be able to generate very specific machines that just get rid of what we want to get rid of. Basically, instead of the damage we see of the microbiome with broad spectrum antibiotics, we'll have much more targeted techniques.
The short answer is: Yes, that's the future. The future isn't quite now, but it's probably sooner than a lot of people realize.
Heading for a 'pre-antibiotic era?' Not so much
BD: Another part of this panel focused on antimicrobial and antibiotic resistance. What do you think is imperative for the industry—both from the R&D side, and also from the collaborative and regulatory side—for addressing this problem that many scientists have basically said could become the healthcare crisis of the coming decades?
PROJAN: I'm going to say some apparently contradictory things. Keep in mind that today, the large maority of bacterial infections are treatable. Yes, there are resistant infections—some that are pan-resistant, there are some bacteria that will become resistant to everything if you keep treating them. Pseudomonas, which affects cystic fibrosis patients, is exactly a case-in-point. It is a serious health threat.
But to state flat out to that we may return to a pre-antibiotic era is incorrect. And the reason why it's incorrect is not all bacteria actually have the capacity to become resistant, much less multi-drug resistant. And there's a reason for that—some are so well-evolved for their particualr niche (such as Treponema pallidum, the bacterium that causes syphillis), that it really cannot adapt to become a resistant organism. It is exquisitely susceptible to virtually all drugs that we have discovered that work against it.
On the other hand, organisms like pseudomonas, which is an environmental organism, it's ubiquitous, has a very large bacterial genome. And it has multiple pathways for evading challenges in its environment. Be they antibiotics, temperature, toxins, high salt concentrations—pseudomonas is very adaptable. It is the bacterial cockroach. So, some bacteria present us with huge problems in terms of multi-drug resistance. Others do not at all. Pre-antibiotic era? Not so much.
But how do we handle those pathogens that have developed multi-drug, and maybe even pan-resistance? And I think there are two different approaches to those that the biologics approach will allows us to answer. One is earlier diagnosis, and maybe even preventing infections before they occur (and that's one of the major reasons I went to MedImmune). The second is to generate a very highly pathogen-specific approach so you don't do collateral damage to the microbiome. You basically create a smart bomb that just takes out the pathogenic orgnism. And again, that's something that we can do with exquisitie specificity with biologics. We just have to spend the time to generate those agents.
Some advice for biopharma: Think even bigger
BD: Do you have any advice for folks in the industry when it omes to this area, or insight about what we should be looking forward to in the coming year?
PROJAN: I'd personally like to see people be much more imaginative than, in general, they are. It's like—generals always fight the last war, and pharma execs always want to discover drugs from 10 years ago. Well, that ain't gonna work.
And that's the beauty of our intellectual property system—you get rewarded for a finite period of time, and then you gotta move on. That, in and of itself, the IP patent expirations really means that if you don't innovate, if you don't evolve as an organization, then you will die. And that's why I love this business, because I know the work I'm going to do tomorrow is going to be completely different from what I did yesterday. It's always about taking the next step.
The technologies we have available are much more powerful than the imaginations we have about how to use them. You quoted Neil Desai in terms of making nanomachines that are going to be the wave of the future in therapeutics—we need more people who think like that, and not say, Oh, that's not possible, we don't have the technology. How can I build that machine that's going to remove a tumor or an infected cell? And that work is ongoing, which is great.
And frankly, maybe old guys like me, we're not going discover drugs as well as we did in the past. But we have to do a job of continuing to stimulate the researchers who are just coming into the chain now, who are just starting their careers, and let them really be imaginative in how they're thinking, and reward them for innovating.
And that's why the BIO meeting is always so inspiring for me, beause you always see these new technologies coming along. There's something called Clarke's law, named after the 2001: A Space Odyssey author Arthur C. Clarke, which is that 90% of everything is crap. And of course, I'm so cynical that I think he's an optimist! The trick is figuring out those 1 or 2% of really great things and how to leverage them.
And that's why I think you go to meetings like BIO, because you get exposed to a lot of ideas, and every once in a while, one of them just clicks, and the light bulb gets turned on, and it's like—Oh my gosh, this is gonna work! Look at what's happening in immuno-oncology right now. Everyone's on that bandwagon, and we're just scratching the surface of what we can do with those technologies.
Stay tuned for more interviews with experts across the biopharma industry this week.