David Bautz, PhD: Welcome to our next episode in our CEO Chat series. My name is David Bautz. I’m a senior biotechnology analyst here at Zacks Small Cap Research. Joining me today is Dr. Kelvin Cooper, CEO of Lakewood-Amedex Biotherapeutics (NASDAQ: LABT). Lakewood-Amedex is developing the Bisphosphocin® class of antimicrobials to address unmet needs in the treatment of acute and chronic infectious diseases. We recently initiated coverage of Lakewood-Amedex with a $12 valuation. Hey Kelvin, thanks for joining me today.
Dr. Kelvin Cooper: Thank you. Thanks, David. Thanks for the opportunity to talk to you.
DB: All right, so let’s dive right in. You’ve previously described this Bisphosphocin® class of molecules as potentially representing a new antimicrobial class. From your perspective, why don’t you tell us a little bit about the key characteristics that truly differentiate this platform from, say, conventional antibiotics or topical anti-infectives that are already on the market?
KC: Yeah, sure. There are probably about four or five things that I’d like to position the class around. First of all, it is a novel mechanism; it’s not the classic antimetabolite or blocking metabolism of microbial cells. What we look for is an agent that actually destroys the membranes around bacteria. These compounds disrupt the membrane, and then the cell contents of the bacteria — or the fungi, where we do have some activity as well — spill out, and the bacteria or microbes die. That happens very rapidly, so that’s the second piece of this: rapid bacterial killing. We’ve run experiments showing that within minutes, at concentrations below what we expect to take into the clinic, we see disruption of the membranes and complete kill of up to a million bacteria within 10 to 15 minutes. We also have activity against biofilm, which is quite unusual; usually, antibacterials and antimicrobials work against reproducing microbes. In the biofilm state, microbes have gone quiescent; they’re quiet, waiting for an opportunity to regrow. Our agents work against those biofilm bacteria as well.
Because of that combination of mechanism of action and speed, we believe there’s a much lower potential for resistance development. We’ve done experiments to try to induce resistance in both MRSA and E. coli and have been unsuccessful with our agent. In comparison, we tried ciprofloxacin, and there was a 2,000-fold reduction in activity. Interestingly, the bacteria that are now resistant to ciprofloxacin are still susceptible to our class of agents. The final piece that’s unusual is local delivery; we deliver our drugs directly to the site of the infection. It limits a bit where we can administer, but at least 50% of infectious diseases start with a local infection, so we can go after skin infections, lung infections, bladder infections, as examples of some of the areas we can go after.
DB: Okay, so to feed off that, the company has indicated that infected diabetic foot ulcers will be your first indication, and of course there are many different indications you could go after. What was it about that indication that made you want to make it your lead?
KC: We’re interested in skin and soft tissue infections, but as you probably know, when you go to a regulatory agency for approval of a drug, you have to pick a specific indication. So, we picked diabetic foot ulcer, and there are several reasons for that. It’s a growing epidemic disease, diabetes, that is. I think there are over 830 million people around the world with diabetes in some form or other.
About 30% of those diabetics will get a foot ulcer at some point in their lifetime, and at least half of those will get infected at least once. It’s quite a large population of people with infections in their diabetic foot ulcers. Unfortunately, there aren’t many good treatments for the initial infection stages. Usually, what happens is a wound or ulcer appears on the foot, sometimes on the bottom of the foot, and because of restricted blood flow and some of the peripheral nerve damage that occurs with diabetes, diabetics often don’t even feel it. So, the foot ulcer is there, it gets infected, and if it’s not treated properly, it could give rise to serious infections and, eventually, amputations. Because there’s no really good treatment for those initial infections — even though oral antibiotics are prescribed, there’s no good clinical evidence that they actually work — going directly to the site of the infection could help. We believe it’s a high unmet medical need, and that’s what led us into this specific indication.
DB: Okay. Can you give us a few details about what the trial will involve, and what you would consider a successful outcome for this study?
KC: Yeah, there are a couple of things we would want to count as success. One is a good safety profile: no adverse skin reactions to our drug, and no systemic issues from giving our drug, although it’s topically given. For efficacy, we want to see a clear reduction in pathogen counts. We are taking biopsies of the foot ulcer at the beginning, middle, and end of the study, where we will count the pathogens, and we’re looking for at least a two-log reduction in pathogen count as a success. We’d also like to see a dose-response curve if at all possible. We’re going in with three doses — a 2% gel, a 5% gel, and a 10% gel — given twice a day for two weeks.
We’d like to see a clear dose-response curve, which would help us select the dose for additional studies. And then finally, although it’s really a secondary endpoint, it would be nice to see a positive impact on wound size. That’s a stretch, because we’re really looking at treating the infection. But it’s known that if you don’t treat the infection, the wound has no opportunity to heal. So, if we can treat the infection, there is an opportunity for the wound to start healing.
DB: As you know, many of these infected diabetic foot ulcers involve polymicrobial infections along with significant biofilm formation. How important do you think the anti-biofilm activity of your compound could ultimately be, clinically?
KC: I think that’s a key element of what we have with this class of agents. I think at least 80% of infections are polymicrobial, so we’re taking account of that. And 15-20% involve MRSA, so those are the resistant organisms. But about half have some element of biofilm, and biofilm, unfortunately, gives rise to persistent or recurrent infections. So the infection may appear to go away, but the bacteria are there, quiescent in the biofilm, and once you take away any treatments, they will start up again and reinfect. So, I think it has the potential to be key in treating infections in the initial stages.
DB: Do you ultimately envision Bisphosphocins® being used as monotherapy or alongside systemic antibiotics?
KC: It’s theoretically possible that they could be used alongside existing antibiotics. We haven’t yet done the studies that would be needed to run those clinical trials, but theoretically, there is a possibility of using them side by side, or together, to prevent the infection from progressing to deep infections — to bone, deep tissue infections, and eventually amputations. The potential’s there, but we need to do those experiments to prove it in the clinic.
DB: From a regulatory standpoint, since Bisphosphocins® are a novel class of molecules, are there any additional regulatory considerations compared to traditional anti-infective development programs?
KC: I think it depends on what we would like to be able to claim. If we are trying to claim that these agents have a much lower potential for resistance development, from a regulatory perspective, they will want to see us prove that, or at least give a very good indication that we’re not seeing resistance develop in patients. As a new class of agents, they’ll also be very interested in long-term safety studies. So I would imagine during Phase 3, where you go to many more patients, safety signals are going to be a key element that the FDA or any other regulatory agency will want to see. I can also imagine that, assuming we get all the way through to commercialization, there will be post-approval studies needed, both for efficacy and safety, and also following up on resistance emergence. Resistance is sort of the number-one topic people want to think about when they’re using antibiotics.
DB: Right. So, to follow up on that, have you seen any additional interest, say, from larger pharmaceutical companies, many of whom have moved away from the anti-infective space, given the continued threat of antimicrobial resistance?
KC: There are a few companies that still maintain an interest in the area, but it has unfortunately really faded away. I started my career at Pfizer working on the antifungal program, where fluconazole and voriconazole were discovered as part of that team. It’s changed dramatically since those days because of the resistance issue, and many of the larger pharma companies have pulled out, primarily because the commercial value isn’t there from their perspective. The issue is that if you discover, develop, and then commercially launch an antibiotic of a known class, you’ll likely see resistance emerge if it’s widely used. So, typically, these compounds are put on the shelf and held in reserve for serious infections, because commercially, that’s not very viable. That’s where we hope to show that our compounds don’t have that resistance issue.
They’re broad-spectrum; you could use them immediately in any infection because they act rapidly and, we don’t believe, are not likely to have an effect on resistance — and that’s why we think interest could come back again. There’s also the PASTEUR Act, which was reintroduced earlier this year in Congress, which looks at how the government can promote research into antimicrobial resistance, recognizing that it’s a very serious problem. If that bill were passed, I think it would spur a lot more development and interest in looking for novel antimicrobials.
DB: Yeah, absolutely. We’ll keep an eye on that. So, as you mentioned, you’ve had a long and storied career. What gives you confidence that this Bisphosphocin® platform could ultimately become clinically meaningful?
KC: Yeah, I think the best indicator here is that infectious disease programs have the lowest attrition, or the highest survival rate, from discovery through to commercialization. The key reason for that is that animal models of infection, if done correctly, and the drug that’s being administered, whatever the route, can get to the site of infection and actually kill it, and that translates to the human situation in a highly reproducible way. Again, if you can get the drug to the site of the infection in humans at an appropriate concentration, it should work as an antimicrobial. So again, success rates are much higher with antimicrobials, from discovery through development. You have to clear issues of safety, and we’ve already done an initial topical safety study. Topical drugs tend to have lower side-effect potential anyway, which again gives us some confidence that Nu-3 will survive from a safety perspective. We just need to prove that it’s got the efficacy.
DB: All right. So, to close, what milestones do you think investors and potential partners should be watching for most closely over, say, the next year to eighteen months?
KC: I would say the first milestone to look for is the start of our clinical trial. We’re expecting to start that very shortly, and we’ll be announcing it when we do. It’s a fairly short, smallish study with very clearly defined quantitative endpoints that will show whether the compound is actually working. We expect proof-of-concept, top-line results to come out at the end of this year or the beginning of next year.
Those are the near-term milestones. Longer term, assuming success there, we’ll be looking to put into clinical trials a Phase 2b trial of the same drug, looking at once-a-day versus twice-a-day dosing, with the appropriate dose helped by selection from this Phase 2a, versus placebo — which is clearly what regulatory agencies want to see: that your drug is better than placebo, and at least equivalent to other antibacterials. So those are the key milestones. That Phase 2b study would start sometime toward the end of next year.
DB: Right. Sounds good. Well, Kelvin, thank you for joining me today. We appreciate this overview.
KC: Thanks very much, David.
SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR.
DISCLOSURE: Zacks Investment Awareness (ZIA) is a Zacks SCR product. The Zacks SCR analyst conducting this Chat hereby certifies that the views expressed accurately reflect the personal views of the analyst about the subject securities and issuer. Zacks SCR certifies that no part of any analyst’s compensation was, is, or will be, directly or indirectly, related to the recommendations or views expressed in this Chat. Zacks SCR believes the information used for the creation of this Chat has been obtained from sources considered to be reliable, but we can neither guarantee nor represent the completeness or accuracy of the information herewith. Such information and the opinions expressed are subject to change without notice.
This text is not a verbatim transcript. This transcript has been edited and does not reflect the video-recording exactly. You may find the video recording in its entirety here. Full Disclaimer HERE.
