Good morning, everyone, and thank you for joining the HC Wainwright 26th Annual Global Investment Conference on September 9th-11th , 2024. My name is Brooke Katsaf, and I'm an HC Wainwright analyst on the corporate access team.
We're confident we are going to be able to provide value to you with over 600 companies presenting at this conference in multiple sector tracks devoted to life sciences, cryptocurrency, blockchain, and fintech, technology, media and telecommunications, clean tech, metals and mining, and growth.
HC Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts and over 636 companies covered across all sectors. Please visit hcwco.com for more information.
Please join us for one-on-one meetings, corporate presentations, and panels that will be available live and streaming on September 9th-11th . With that said, have a productive and enjoyable day, and I'd like to introduce our first presenter. I'd like to welcome Jonathan Solomon, who is the CEO of BiomX.
Thank you, Brooke, and thank you for the folks at H.C. Wainwright for having us here. Let me jump through the presentation. Of course, the safe harbor statement. But basically, the big event that took place in the last few months has been the acquisition and merger with Adaptive Phage Therapeutics and concurrent $50 million financing.
This position, the joint company, is actually a leader in phage space. We have two Phase II programs, which are expected to read out in 2025. There's quite a lot of extensive clinical experience with almost 80 compassionate use cases, numerous clinical studies and INDs. Some of the top-tier investors in the field, Deerfield, the AMR Fund, OrbiMed, and the CF Foundation. Significant non-dilutive funding, so over the years, almost $40 million have been received from the Defense Health Agency.
A very large phage bank, which is the basis for these compassionate use cases, advanced CMC, and even APT last year made it to Fierce 15. If you look at the company, the combined pipeline provides two significant inflection points, so the first program is cystic fibrosis.
We are looking into bacterial infections driven by a bacteria called Pseudomonas aeruginosa, which is the leading cause of morbidity and mortality in these patients. These patients have been chronically treated on antibiotics and now have a lot of antibiotic resistance, and there are estimated 17,000 patients in the U.S. and Western Europe alone that harbor these chronic infections, a nd that brings commercial opportunity north of $1.5 billion.
The company had some significant readouts. In November 2023 w e've actually shown, in a Phase II-A Study, that 14% of patients treated only for 10 days with our approach actually got rid completely of the bacteria, and that did not occur at all in placebo. So that was a significant outcome in the study, and I'll spend some time on it.
We've also seen some initial signals of improvement in pulmonary functions versus placebo, as well as in patient-reported outcome. We're gearing up for the Phase II-B, that is expected to read in the third quarter of 2025. The second program, diabetic foot osteomyelitis. Here we're talking about a humongous unmet need, with 160,000 lower limb amputations in diabetic patients every year in the U.S. alone.
The most common pathogen is a bacteria called Staph aureus, and that represents commercial opportunity north of $2 billion. BX211 is now in a Phase II, which is ongoing, expected to read out first quarter of 2025, and that study actually is based on numerous experience that the company has gained from these compassionate use cases. We are publicly traded on NYSE, with cash runway until the end of 2025.
If you're looking at the pipeline, so basically, I've mentioned the CF program, with a readout in third quarter of 2025, and BX211, diabetic foot osteomyelitis, with an initial readout already in the first quarter of 2025, another readout a year later, at the beginning of 2026, and a potential for some additional programs.
A little bit about phage. So phage is experiencing a renaissance. There's been our data, some of our competitors, Armata, another public company, is gonna report data soon, and some reported some initial data early this year. Furthermore, another private company, Phage, has reported data positive in Locus, so the modality is picking up. Interestingly, phage is basically nature's precision tool to go after bacteria.
So it's a virus that kills bacteria. It's exquisitely specific, so a phage for one type of bacteria is not gonna infect another bacteria. It's got to be a perfect match. It's sort of a lock-and-key mechanism. The mechanism of killing bacteria is orthogonal to antibiotics, so the phage don't care whether a bacteria is extremely resistant to antibiotics. It's completely different mechanisms.
One of the big reasons that antibiotics are not working is the formation of biofilm, which is a sticky mixture of proteins and carbohydrates that some phage have actually evolved to break down. Phage amplify, so you think about it, when a single phage infects a single bacteria, if you wait 30 minutes, in the case of some of the common bacteria, you're now gonna get one dead bacteria and 100 phage.
If you wait yet another 30 minutes, you're now gonna get 100 of bacteria and 10,000 phage. So when the motion starts and this propagation starts, it's an extremely effective tool to go after bacteria, and very specific. Also, there is quite a lot of safety, track record.
So the FDA has acknowledged in three public workshops that phage is a safe modality that does not require animal studies or healthy volunteers, and of course, a lot of experience by now in the clinic. So I'll zoom in on the two programs. BX004 is going after cystic fibrosis. So CF is an inherited disease caused by a mutation in the CFTR gene that basically damage all the mucosal organs of the body.
The leading cause of death is respiratory failure, and that's associated with these nasty infections that stop responding to therapy. So there are 33,000 patients in the U.S. alone with CF, and as we said, roughly 1/3 of them harbor these bacterial infections driven by Pseudomonas.
There's quite a lot of data that ties the presence of Pseudomonas colonization with a worse clinical outcome, lower, worse. You see here lung function, lung volumes, and volumes measured by FEV1. Literally, when you look in these lungs of these patients, you see these bacteria, a lot of inflammation around them.
They form these biofilms that once they form, they stick to the lungs and bacteria, antibiotics cannot penetrate and damage the bacteria. In the '90s, before there was so much antibiotic resistance, antibiotics performed very well. You can see here from studies of tobramycin, the gold standard, in the mid-'90s, that a reduction in a very nice reduction of the bacterial load around two logs.
So that's like sometimes a 99% reduction of the bacterial load, and that translated to a clinical improvement in lung function, which is an order of magnitude same as the CFTR modulators, the Vertex drug. Quite a big effect when there wasn't that much antibiotic resistance. Obviously, today, the situation is very different. When you look at the patient journey, what you see is that in the initial stage of the disease, infancy, sometimes a kid would have an infection, gets treated with antibiotics, it goes away.
In childhood, there's more and more infections and more of these common episodes of infections. They're treated with antibiotics, but the rate of occurrence increases. The bacteria become antibiotic resistant. There are now biofilms, which are forming in the lungs, and then the patient enters the chronic stage.
Chronic could be a 20-year-old patient and even, you know, a teenager. At that time, at that point in time, they're basically taking antibiotics all the time, and the antibiotics are not really improving their condition. They're just kind of keeping it as stable as they can. Again, the antibiotics are not really having the effect they used to have because of antibiotic resistance and because of the formation of biofilm.
We've actually executed two clinical studies. Part one was nine patients, two on placebo, seven on treatment. They were treated with first day of placebo, second day, a low dose, third day, a high dose, and then four consecutive days of high dose of phage. We've enabled patients that were taking antibiotics, whatever they were. We wanted to make sure they had high levels of bacteria, that the bacteria were sensitive to our phage cocktail, and we had no restrictions on CFTR modulators.
So majority of patients were actually on CFTR modulators. The results were quite surprising. Already in the part one, which was published a year ago, and here we saw no safety issues. But what's interesting, if you look on the right, on the graph in red, you see the placebo response, something like a zero point three log reduction.
Anything up to, like, half a log reduction is considered, you know, noise and a well-behaving placebo group. In the treatment, we did see an overall effect of one point four log, so a 95% reduction in the bacterial count after effectively treating for four days.
I nterestingly, one patient had a 3.3 log reduction, that's a 99.6% reduction in bacterial load. Two patients had, you know, 99%. So really interesting data on a very short duration period, so far. That gave us confidence to move forward to the next study, the part two, which was published in November. Here again, we've intended to enroll 24 patients. There was quite a lot of excitement on the clinical sites, so we recruited 34, 23 got phage treatment, 11 got placebo.
Now, we gave them 10 days of treatment, twice a day. Again, allowed patients on whatever antibiotic they were taking. We made sure patients had high level of the bacteria, and they were sensitive to our phage cocktail, and again, no restrictions on CFTR modulators, and the majority of patients were on CFTR modulators.
When looking into the antibiotic regimen, majority of patients were on continuous treatment, meaning the same antibiotic all through the treatment period. T hen we add some that were alternating and others that were cycling. Alternating means they were taking one month of one type of antibiotic, the other month, another type.
Cycling, they have a drug holiday, and then they take antibiotic and then a drug holiday again. We made sure that it's synchronized, so we start the phage treatment when the patient started a new antibiotic. Of course, it doesn't really mean much when it's continuous treatment. They're just took whenever they had the treatment. High-level data, so we did not see any adverse events. Again, encouraging, not surprisingly, no phage is safe.
As I mentioned before, the most exciting part of the data was that three out of 21 patients basically converted to culture negative, meaning they had no bacterial bacteria detected in their sputum after only 10 days of treatment. That was exciting, did not occur at all in placebo, and that's the reason the KOLs were excited.
We did see some early evidence, albeit these are a small number of patients, of improvement in clinical parameters, FEV1, so lung volume, as well as in patient-reported outcome. When we tried to quantify the levels of bacteria, we saw a lot of variability. In a pre-specified group, which was those who are taking inhaled continuous antibiotics, we saw a dramatic reduction, so a three-log reduction of bacterial count, exceeding the one and a half log that we saw in part one.
When we look at those patients that were alternating or cycling, we saw a lot of variability that was driven already in the placebo by the fact that we're kind of fluctuating the antibiotic. We didn't see any evidence of phage resistance, and basically, that gave us confidence to move forward to the Phase II- B. Just zooming into the bacterial conversion, as I mentioned, that's a very dramatic outcome.
So you can see the three patients that converted were patients that were infected for many, many years. Two of them had extremely high bacterial counts, so this is not something that spontaneously happens. Suddenly we saw a reduction in the bacteria, which is extremely, extremely dramatic. As a benchmark, you do not see that often in, like, eight studies that tobramycin did in the 90s'.
There was only one study that reported 10% of patients having bacterial conversion, and that's after three months of dosing. A nother example, Insmed, again, in another lung infection, showed that 20% of patients converted to bacterial culture negative after four months of treatment, and that justify a very hefty price tag for a drug that can have that effect.
Interestingly, this is not the first time we saw this effect, because if you go back to the data that we've seen in part one, that single patient that had the 3.3 log reduction, also, the physicians reported a few months later that this patient had also got rid of his bacterial infection. So again, same ratio, one out of seven, 14%.
So really encouraging data that shows that even though we're dosing for a relatively short period of time, we are seeing initial evidence that some of the patients are completely getting rid of the bacteria, and that can have the potential to dramatically change the course of disease. Also, just looking at the clinical improvement, so again, these are small number of patients for such a readout, but we are seeing some preliminary signals.
FEV1 measured on bacteria on lung volume. We're looking at those patients that have an FEV1 below 70%, which is standard in the industry, to try to find those patients that actually have the potential to improve their treatment. You do see improvement around 5% and above, which is, you know, deemed potentially clinical meaningful. Again, big error bars, so this is just an initial study.
In the patient-reported outcome, we are seeing even a more dramatic effect. So the effect size is almost nine points improvement in patient-reported outcome. Anything above four points is deemed clinically meaningful, and this actually reaches, almost reaches statistical significance, albeit the small number of patients.
So again, encouraging, preliminary, and we're excited, getting ready for the next study. The big difference from the Phase II-B is that we're dosing for two months compared to the 10 days. We are aiming for 60 patients, randomized 2-1 , and again, we will allow short courses of inhaled antibiotics, patients with high bacterial counts, and no restrictions on CFTR modulators.
Moving to BX211, so basically, a very high unmet need. What happens in these diabetic patients that have neuropathy and poor blood supply is that easily a superficial ulcer can develop into a big infection that gets to the bone.
Currently, standard of care is antibiotics, offloading, debridement, anything they do, and that results still in a relatively poor outcome, with 30%-40% of DFO cases result in amputation. So a serious unmet need, usually driven by a bacterial Staph aureus.
Now, historically, antibiotics have not worked very well because of the lot of biofilm, which I mentioned before. So the presence of biofilm limits the ability of antibiotics to penetrate into the bacterial colony. There's poor blood supply, so IV antibiotics, oral antibiotics also don't get in high concentration to the site of action.
On top of it, there is quite a lot of antibiotic resistance, and that actually provides the opportunity for phage therapy that could potentially overcome all these issues. Phage can be selected to have antibiotic capabilities. The fact that phage amplifies, as we mentioned, might make it more efficacious in low concentration, because once the phage found their prey, the bacteria, they can start amplifying, and on top of it, phage overcomes antibiotic resistance.
That could be the basis that there's actually quite a lot of experience treating patients with diabetic foot osteomyelitis successfully with phage therapy. One publication of 12 cases that were treated with DFO, 11 showed significant improvement and prevention of amputation. So again, this is a compassionate use case without the proper controls, but encouraging data.
I n general, osteomyelitis sticks out as one of these indications that there's quite a lot of data that phage therapy seems to be working with a great effect, with the disclaimer that I said. But that gave the basis for the ongoing study, the Phase II in DFO. So this is a study in which patients are treated for 12 weeks.
The first week, they get an IV and a topical administration, followed by topical administration for every week up until week 12. We're aiming for 45 patients. The majority of patients have been enrolled, and we are expecting to see the first data of week 13 in first quarter of 2025. What we're looking for is a reduction of the study of the ulcer size.
So the assumption is that based on metadata, ulcer shrinks around 40% in the placebo group, because these guys are on top of standard care antibiotics, and we're hoping to get an effect of around 70% with the treatment. So that would be the primary endpoint that we're looking into.
We will look into ulcer healing, which is an indication that the infection is being resolved at the bone and inflammatory markers, and of course, we will follow patients for a longer time. Again, this is more descriptive, because for amputation and free survival times at week 26 and 52, we need more patients.
But a clear signal on reduction of the size of the ulcer will give us the green light to hopefully move forward. So that's it. Thank you very much, and again, thank you for the folks at HCW for hosting us.