BiomX Inc. (PHGE) Earnings Call Transcript & Summary

Good morning, and welcome to the BiomX conference call to discuss results from the company's ongoing Phase Ib/IIa trial in cystic fibrosis. [Operator Instructions] I would now like to turn the call over to Marina Wolfson, Chief Financial Officer of BiomX. Please proceed.

Thank you for joining us today to discuss the results from Part 1 of our ongoing Phase Ib/IIa trial, evaluating BX004 for the treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis or CF. Earlier today, BiomX issued a press release detailing results from Part 1 of our study that became available just after 6:30 a.m. Eastern Time, and can be found on our website at biomx.com. A replay of this call will be available on the Investors section of our website. Before we begin, I'd like to review the safe harbor provision. All statements on this call that are not factual historic statements may be deemed forward-looking statements. For instance, for using forward-looking statements when we discussed on the conference call, potential market opportunities, the design, a, expected timing and interim and final results of our preclinical and clinical trials; the potential benefits of our product candidates and the potential safety or efficacy of BX004. In addition, past incurrence of clinical and clinical results as well as compassionate views are not indicative and do not guarantee future success of our clinical trial. Except as required by law, we do not undertake to update forward-looking statements. The full safe harbor provision, including risks that could cause actual results to differ from these forward-looking statements are outlined in today's press release, which, as noted earlier, is on our website. Joining me on the call this morning is Jonathan Solomon, Chief Executive Officer of BiomX. With that, I will turn the call over to Jonathan.

Thank you, Marina, and good morning, everyone. We are very pleased to have the opportunity to discuss the positive results from Part 1 of our ongoing Phase Ib/IIa trial, evaluating our novel phage product, BX004 for the treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. As announced in our press release issued earlier this morning, several patients receiving BX004 therapy experienced a notable reduction in bacteria compared to patients who received placebo. Since the primary aim of Part 1 of the trial is to demonstrate safety and tolerability in relatively few patients, we're positively surprised and excited about these results, which we should share in greater detail later on the call. As a reminder, BiomX is developing BX004 as a treatment for CF patients who suffer from chronic pulmonary infections caused by Pseudomonas aeruginosa or PsA, the main contributor to morbidity and mortality in patients with CF. Our ongoing Phase Ib/IIa trial is composed of 2 parts: Part 1 evaluate the safety, pharmacokinetics and microbiologic activity of BX004 in 9 CF patients in a single ascending dose and multiple dose design. We will discuss these results momentarily. In part 2 of the trial, which we've already started dosing patients, is designed to evaluate the safety and efficacy of BX004 in 24 CF patients, randomized to a treatment or placebo in a ratio of 2:1, and we anticipate reporting data from Part 2 of the trial in the third quarter of this year. Before discussing the details on Part 1 of the trial, I'd like first to take just a few minutes to review the significant unmet medical need in CF that we hope to address with BX004. Chronic PsA infections are widely recognized as a persistent problem due to growing antibiotic resistance, which drives higher mobility and mortality in CF. As this chart shows, during infancy and through childhood, these inflection can be largely controlled with use of intermittent antibiotic therapy. Unfortunately, as adolescent patients move into adulthood, the effectiveness of antibiotic therapy starts to decline due to resistance from prolonged and repeated exposure to antibiotic therapies. In addition, patients also develop biofilm in their lungs, making the infection much more difficult to treat. Biofilm is a polysaccharide mesh that the bacteria secrete and embed themselves in and serves as a defense mechanism against anti-bacterial agents. As a result, there is a significant unmet need for CF patients suffering from chronic PSA infections, which is estimated to be approximately 17,000 patients in the U.S. and Western Europe alone. To address this unmet need, BiomX has developed BX004, our proprietary phage cocktail that is designed utilizing our BOLT platform to specifically target chronic PsA lung infections in CF patients. By taking a cocktail approach in our phage design, BX004 has shown in vitro to be effective against resistant strengths of PSA bacteria. In addition, preclinical data has also shown that BX004 enables breakdown of the biofilm, which could prove to be a major benefit in helping reduce picture burden. BX004 is administered using a nebulizer device, which converts the phage product into an aerosol for efficient delivery directly to the lungs. This type of device is commonly used by CF patients to administer antibiotics. The potential benefits of BX004 could be a reduction of bacterial burden driving improved lung functions that can in turn also reduce patient exacerbation and hospitalization. We believe the commercial opportunity for BX004 is significant with approximately 17,000 CF patients in the U.S. and Western Europe alone and commanding a market potential of over $1 billion, based on the target patient population as provided in the CFF 2019 Registry and our assessment of pricing based on existing comparable therapy as further detailed in our corporate presentation. I'd now like to discuss the trial design of our ongoing Phase Ib/IIa study. Part 1 of the study included 9 CF patients with chronic PsA infections. The primary purpose was to determine BX004's safety and tolerability and exploratory objectives such as the pharmacokinetic profile and microbiologic and clinical activity. Lung function was tested for safety and efficacy. It is important to note that due to the short treatment cycle, we do not expect to see an improvement in lung functions. Endpoints for Part 1 included the assessment of safety, tolerability, impact on PsA burden, CFU, sputum pharmacokinetics, FEV1, a cystic fibrosis questionnaire revised or CFQ-R and a chronic respiratory infection symptom score or CRISS. With respect to dosing, 7 patients received nebulized BX004 phage therapy, and 2 CF patients received nebulized placebo. As previously mentioned, all 9 patients received all doses of study drug or placebo and were assessed on at several time points, including their last clinic visit at day 15 or 7-day post treatment. Single ascending dose was followed by multiple doses so that impacted the treatment arm we've seen the full dose only for 4 days. Safety was assessed and confirmed before each dose escalated to the next level. Part 2 of the Phase Ib/IIa trial will also assess safety and efficacy measurement similar to Part 1, but we'll do so in 24 patients. 16 patients will receive nebulized BX004 therapy and 8 will receive placebo in the 2:1 randomization. In addition, treatment duration will be extended over a 10-day period with twice-daily administration of the high dose versus the 7 day period of escalating doses in Part 1. I am pleased to report that we've already enrolled patients in Part 2 on the trial. Without question, the most exciting results in Part 1 study was a notable bacterial reduction observed with patients who received BX004 compared to placebo. And these 2 charts visually demonstrate this difference. As the chart on the left clearly shows 5 to 7 CF patients who received BX004 showed notable reduction in bacterial load. By contrast, the chart on the right indicates the 2 CF patients that received placebo showed very modest reductions in bacterial load. More specifically, at day 15, patients treated with BX004 had a mean reduction in PsA colony forming units, or CFUs, compared to baseline of 1.42 logs. For the placebo-treated patients, the mean reduction of PsA CFUs was only 0.28 log. Needless to say, we were very pleased by the magnitude of reduction in bacterial load. Considering the shorter course of treatment in Part 1, these results exceeded our internal expectations and give us a degree of optimism that longer course treatment of BX004 can lead to clinical improvements in lung function, and we hope to demonstrate this in Part 2 of the study. The next slide highlights additional results from Part 1 of the study. Not surprisingly, the safety for BX004 therapy was very clean. No significant or treatment-related adverse events were observed. I just discussed, the reduction of bacterial load seen with BX004 therapy were impressive. It should also be noted that the reductions in bacteria for both the BX004-treated patients and the placebo-treated patients were on top of standard of care inhaled antibiotics. Phage detected in all patients treated with BX004 during the dosing period, including several patients with detectable phage up to day 15, one week after the end of therapy. Importantly, among BX004-treated patients, there was no emerging resistance to BX004 during or after treatment. Resistance will always remain an important issue in this patient population and due to the cocktail-based approach in designing BX004, we believe our phage product provides orthogonal coverage across potential resistant strains of bacteria. Lung function, as measured by percent predicted FEV1 was tested for safety and efficacy. It's important to note that likely due to the short course of therapy, no effect on percent predicted FEV1 was observed in the first part of this study. To conclude, this represents the first published placebo-controlled study evaluating the cocktail based phage product to show notable reductions in bacterial burden and cystic fibrosis. With that, we'd be happy to take your questions. Operator?

Before I will allow any questions, I will turn it back over to you to make an additional announcement.

I'm also pleased to announce this morning that BiomX has entered into a securities purchase agreement of $7.5 million investment of several investors including BiomX shareholders, OrbiMed and Cystic Fibrosis Foundation. We greatly appreciate the financial support of our new and existing investors. With that, we'd be happy to take any questions.

[Operator Instructions] And our first question is from the line of Joe Pantginis with H.C. Wainwright.

First, let me add my congratulations for BiomX, but also my congratulations because this is a very important day for the phage space. So very nice all around even though it's early data. So a couple of questions, if you don't mind. I just wanted to get a sense. Now that these patients are done with Part 1, are you going to be compiling any additional data from these Part 1 patients?

I think an exciting day for serous patients and the face community and, of course, for us, and we're blessed with a great and dedicated team. So we're extremely excited, as you know. I think there's -- as we've shared the top line data, there's still additional data that we're compiling, I think we plan to present everything at a conference and do a lot of the due diligence because as you -- and analysis. Because as you're seeing, there's a lot of interesting insights on capabilities of the cocktail and resistance and the PK, which was extremely surprising to see phage one week after dosing. So there's a treasure of knowledge here that we will analyze and we'd love to share with the whole community.

No, that's helpful. And then, I guess, from what you have right now, obviously, it's too early to show impacts on FEV, but are there any physician observations or anecdotes on potential impacts or like I said, even anecdotal impacts on breathing capacity at this point, early point or quality of life or any other things to point to observationally?

Yes. So as you noted, this is a very short study, and we've analyzed and sort of followed FEV1 mostly for safety to make sure that nothing kind of going array. There weren't any expectations for effect on FEV1. So far, we haven't seen anything of note, but we're continuing to analyze the data.

And just to make sure, like anything beyond that quality of life or anything other than that a physician might have commented on their particular patient?

Still data that we're analyzing. I think the main focus was obviously safety and tolerability. And we kept on talking about the bacterial load. I think, as you know, the expectations were very modest here, and I think we're so surprised seeing this data, again, as we said, it's early, but the reduction of bacteria are very pronounced, and I think it's quite exciting, right? I think we're finding ourselves at the end of Part 1, we're hoping to be at the end of Part 2 with strong indication of activity of the phage cocktail.

Got it. And my last question, if you don't mind, is, obviously, I mean, just talk to a little bit more macrophage, but does talk to the specifics of 004 here. And that is, look, when you look at antibiotics, a lot of people would consider resistance over time. Can you talk about maybe some of the preclinical work that you've done on 004 with regard to the kinetics of resistance. Do you even see it and how people would look to compare and contrast when considering a future potential profile of resistance compared to antibiotics?

So we always have patience for a great question. So keep it coming. Don't worry about it. And I think it is a very good question. As we've noticed in this study, we've not seen resistant emerge, which is actually very reassuring because our cocktail is designed exactly by these concepts and sort of fundamentals of let's make sure that when we add a phage and we incubate target bacteria and we wait and we see these escapement, we actually add a phage to kind of go after the escapements and kind of iterate that multiple times until we feel that the cocktail is solid and the chance of resistance is very, very low. I think these were the guidelines that we followed and it's reassuring to see it translate to results that we see in the clinical study with the caveats that we all know. It's a small number of patients, and it's -- the duration was effectively only 4 days of twice a week dosing and a few days of single doses before, right? We do have some evidence from published evidence from the capacity use cases that usually in the single-phage administration, resistance did develop. So I think we're closely monitoring it. I think we're encouraged by the data. And we've seen so far translation from the work and the approach that we take in designing these phage cocktail in vitro to what we're seeing in the clinic. I think it's encouraging. That kind of stresses the fact that we need to analyze more and sort of look at longer duration to see how it continues to evolve. But I will say it is encouraging.

The next question is from the line of Michael Higgins with Ladenburg Thalmann.

Jonathan, congrats from me as well on the impressive data. This is really a leading data in phage heading a placebo arm here and roughly fivefold greater reduction in [indiscernible] efforts 15 days is only impressive, especially considering the dosing here. This was 3 SAD days, 4 MAD days. So we're curious what the potential might be if this were dosed 7 days. Obviously, the part 2 here is going to be 10 days. But if you could speak to that. I don't know if sputum was measured prior to the 15 days but just trying to get a sense for efficacy change throughout this study period.

Right, Michael, great question. So I think that's been a constant debate. And as you said, and we spent time kind of thinking and communicating and talking to everyone. This study was first and mostly designed as a safety study, right? So I think that's why you saw this relatively short treatment duration. And as you mentioned, I think we were very surprised and pleasantly surprised on the kind of effects that we see. If you take it to a longer period of time, I think then we need to look at benchmarks, right? And at times, we've spoken about the fact that the kind of data that we see with antibiotics, which can get something between 1.5 to 2 log reduction. Usually after like 2 weeks, and that's where we're starting to see effects after continuous dosing and when we look at a month later, we can see effects on FEV1, right? So I think that's where we're aiming. We want to be where antibiotics were in the 90s before all the resistance developed. I think there's another point that we need to look into because in some ways, if we look at the data from the compassionate use, we do feel that the data that we've just generated actually supports the data that was published in the capacity use, right, and vice versa. So I think we've seen in capacity use that longer dosing can lead to greater reductions in bacteria. Again, there weren't a placebo and you got to take it with all the disclaimer and caution. But to some extent, we feel strengthened actually by the compassionate use data that is being, to some extent, replicated here and vice versa, right? So I think it's exciting. There's kind of a -- I wouldn't call external validation, right, but some external support. And it means probably that a longer duration should lead to a greater reduction in the bacteria in the future.

The other side of the coin being safety out to 15 days and even out to 30 days and now the primary is up to 6 months. But did you see any impact on safety, tolerability as the patients progressed in their dosing?

No, we haven't seen anything related to the drug. Any -- it came pretty clean. I think we -- that's why we've also announced that the DSMB actually approved moving into Part 2, and we've already started dosing patients in Part 2. So it looks very good. I think that's one of the key advantages of the phage, right, being very, very safe, and I think we're seeing the same thing. So we don't see any issue with longer durations of dosing. And again, to some extent, if we rely back on public data, right, there are a lot of anecdotal data of compassionate use treatment with phage, there hasn't been really any safety issues or concern, and we're seeing pretty much the same thing.

Great. Yes, I expect that. That's great. One last one here. In looking at the trial design at this and others, wanted to ask if the patients were on background therapy, if you could give us some kind of sense as to what they were on? How long they're on it? Just trying to get a sense for what kind of background meds these patients were on prior to enrollment.

Yes. So I think for us, it's really important that the patient would be stable in their dosing. So all these patients were actually on a stable regime of antibiotics. We didn't want to see any change in their antibiotic schedule because that would sort of distort the data. So I think for us, it was crucial that they don't sort of change medication that they've been taking antibiotics for a relatively long time. And I think that's what we wanted to make sure that when we give these patients, there are no fluctuations which are driven by the antibiotics, and we can see an effect, which is truly driven by the phage. So that was key. We had -- we have allowed for CFTR modulators and some other medications so long as the patient was relatively stable patient.

The next question is from the line of Kristen Kluska with Cantor Fitzgerald.

My congratulations on these data sets. Could you talk a little bit more about the cadence of the bacterial reduction as well as the time to onset. Essentially trying to figure out how quickly it worked, if it was in line with expectations here? And what you suspect could happen with a little bit longer treatment duration like you are looking at in Part 2?

For sure, and Kristen, it's great to connect, especially in happy occasions like this one. So I think what we know and we're analyzing, and again, there's still this kind of early data, we'll obviously share more. But I think based on the information that we know in vitro and that was published for phage, phage has a slower onset than antibiotics. That's what we've seen. There's mechanism, which are at play here like breaking down biofilm, which is an advantage of the phage. To remind you, our phage cocktail is designed to have anti-biofilm capabilities, and we mandate that the cocktail is tested for that, has the capability in vitro. Those are kind of for us, one of the key criteria to move forward. So we do see a bit of slower onset with phage. It takes a few days to see an effect usually. That's usually what we see in vitro and that's what we're seeing even in, in vivo studies that we're doing. So things do take a bit longer than typically antibiotics. I do think that's where we've heard also from experience of compassionate use that they usually -- they need -- they wait like a week to 2 weeks until they're seeing maximum effects. So what we're seeing here, sort of, again, in line with what is reported from the compassionate use, but I think now we're trying to do it in an orderly fashion. We do think that, again, if we use a benchmark for some of the data out there that longer duration in the compassionate use might lead to even greater reductions, right? Again, these are compassionate use. I think it justifies for sure, moving into the 10 days dosing and potentially we could get greater reduction. So we'll closely monitor that. And that opens, I think, the question as we analyze that data: what is the kind of dosing regime that we want to see in a pivotal study, right? Because usually, you talk about months of dosing in some of the antibiotic studies in the '90s, think as we analyze all the data, and we're taking samples from the bacteria and we're analyzing the bacteria and every piece of information that we can get, I think we'll use that all to inform the decision on the dosing regime for the pivotal study.

Okay. Maybe just a big picture question. Obviously, important for this indication in general, but you've now collected data looking at phage delivered via a different administration here nebulized. So maybe talk about what these data show in terms of the ability for phage therapy to be successfully delivered this way and how that might open the door perhaps down the future?

You bet. I think it's a great question because I think we've learned and had -- in the past, when we look at our acne studies, we did see that topical delivery is much more challenging with a large molecule like a phage to go -- when we needed to go deep into the sebaceous gland. Here, again, choosing this indication, there was some preliminary evidence that delivery seems to be working, right? Again, these compassionate cases have been around for a few years. There was evidence of reduction in sputum. So we felt relatively that there is some ground to move forward. We did a lot of work into the nebulization and making sure that the formulation, the droplet side, everything is suitable to get deep into the lungs and try to optimize using the resources we had at hand. And I think what we're seeing here, and I think that is so exciting, right, is evidence that phage can reduce bacteria from the lungs. When we compare it to placebo, we're seeing -- it seems to be a very notable effect. So that actually gives us comfort that delivery -- nebulized delivery to the lungs should be working. And I think as we think about it, and as I said, we're sort of finding ourselves ahead of where we wanted to be. We thought this kind of data comes in only at the end of Part 2. It does open the question of like, okay, there's more we can do, right? We can think about using this phage console for Pseudomonas in other indications, which share the same target bacteria, which is colonized on lungs, right, as now that we know that we can get to where the bacteria are. And it also means that we know in CF patients that there are other bacteria that are infecting these patients. We can pursue other bacteria as well in this patient population and others. So I do think it's exciting because it opens the door to nebulized delivery of phage for this bacteria in other indication as well as other bacteria in CF and other indications as well.

[Operator Instructions] The next question is a follow-up from the line of Michael Higgins with Ladenburg Thalmann.

Just a follow-up on the last comment made on potential for other indications. Might you adjust the cocktail despite those being Pseudomonas infected patients? Just curious if you can give some thoughts.

Michael, just to make sure it's the question about using the same cocktail for other indications or modification in the cocktail?

Yes, both, basically. Would you adjust what phages are in the cocktail if you go out for other Pseudomonas-specific patients?

Right. Got it. So I think it kind of goes back to the questions of resistance and host range, right? When we develop a cocktail, the way we approach it is, first and foremost, get samples from across the world, analyze them and make sure that we're building a cocktail that provides broad coverage as well as overcome resistance, right? And these are all work that we do in-house. There's a lot of wet testing, analysis, sequencing and a competitional platform that in the end comes out with a cocktail, which is optimized to the data set that we've started and we received. I think now as we're thinking about some additional indications to potentially consider, then you kind of do the same process, right? If we're looking at another indication, you get patients samples from across the world. You make sure that the bacteria that we're seeing are not very different from the bacteria that we've optimized initially. If we do, we could consider to add another phage or make modification, which we -- given that we have all the platform in-house, we can do that rather quickly. And if it passes all the stages of the BOLT platform, we can then kind of move forward to a study. So that translates to if we're saying, hey, there's another indication with Pseudomonas. We'll get patient samples from across the world, run the existing cocktail and say, can we use the existing cocktail, yes, no. If no, we can modify it. If yes, we can move straight, right? As a reminder, again, with phage, you don't need to do safety studies, as noted, for healthy volunteers, we can kind of move very quickly, and I think this data kind of builds more on the safety that we're discussing. And if it's a new bacteria, then again, it's pretty much the same process. We get, again, samples from across the world. We analyze everything. We find phage, and we can do that actually rather quickly. We can actually -- given the platform that we have and sources, we can find phage, optimize the cocktail and then within 12 to 18 months, even in a new indication that we just start with samples, we're ready to go with GMP grade material ready for a clinical study.

That's super helpful. Obviously, there are other CFPA studies enrolling. Others are enrolling the patients with FEV greater or equal to 60% predicted normal, yours enrolling patients with FEV 40% or more predicted normal. So curious as to why there may be a difference there in the designs and the enrollments and then the containing question being if you can provide the baseline FEV percent of your patients.

Sure. So to answer, I think we took anything above -- patients with FEV above 40. I think -- again, the main objective of this study was just to show safety, right, which is important. So -- and that's how we thought about it. I think given -- going forward, given the data that we have now in hand, it does warrant thinking about how do we proceed? Are there any changes in the Part 2? Should we add another arm just because it's exciting, right? We're seeing the mechanism or at least some evidence of the mechanism translating from what we're seeing in vitro to the clinic. And I think that warrants thinking given the quality of the data to see what are possible next steps. As I said, we're sort of finding ourselves at the end of Part 1 where fortunately, we're hoping to be actually only at the end of Part 2.

I wasn't expecting that answer. That's very helpful. And I noticed you didn't mention the FEV baseline, may have just overlooked it. But when you suggest potential changes to Part 2, is that related to FEV percent or other measures as well?

Not necessarily. I think the Part 2 sort of gone on its way, but I do think this kind of data weren't thinking whether we should add another arm, whether, as we said, other indications. So I think that's -- it's a kind of data that, again, the team is executing on Part 2. We're expecting to be on time line, but I think we do need to think about whether there's any additions that we should do for sure.

Okay. That's helpful. Another question as it relates to other CFPA studies is systemically dosed antibiotics. I asked earlier background, I just wanted to zero in a bit on the systemically dosed antibiotics as background therapy. Any comments as to what those patients were on.

I think it's on the protocol. I'm not sure it was publicly disclosed, but they were on -- they were chronically being treated with antibiotics kind of standard, but I think all that information will be published at the conference.

Okay. We look forward to that. And then one last one here. I believe you were due $2 million in equity from CFF for completing Part 1. Has that been received? Is that to come in here in Q1?

Sure. We rolled everything into the pipe that we've just announced.

I see. So part of that $7.5 million was $2 million from CFF for the Part 1?

Yes.

Okay. Appreciate it.

At this time, I will turn the floor over to Jonathan Solomon for any final remarks.

So thank you again for joining us this morning. We're obviously very pleased with the results from the first part of our CF trial. Based on these encouraging data, we believe BX004 has the opportunity to address a significant unmet medical need for CF patients who're battling with these chronic and life-threatening infections. We look forward to providing program update in the third quarter of this year when we expect to report the results of Part 2 of the study. Have a wonderful day, and please reach out to us if you have any questions. Thank you.

This will conclude today's conference. You may disconnect your lines at this time, and have a wonderful day.