BiomX Inc. (PHGE) Earnings Call Transcript & Summary

Good morning, and welcome to the BiomX conference call discussing top line results from Part 2 of the company's 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 top line results from Part 2 of our Phase Ib/IIa trial, evaluating BX004 for the treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis, or CF. Earlier today, BiomX issued a press release announcing top line results from Part 2 of our study, just after 6:30 a.m. Eastern Time, which can also 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, we're using forward-looking statements when we discuss on the conference call, potential market opportunities, the design, aim, expected timing and interim and final results of our preclinical and clinical trials, including the potential to initiate a pivotal Phase IIb/III trial, regulatory feedback and availability of sufficient funding for such trials; the potential benefits of our product candidates and the potential safety or efficacy of BX004 and specifically our belief that extended treatment with BX004 may lead to a significant improvement in clinical outcomes for the patient population. In addition, past and current preclinical and clinical results as well as compassionate use are not indicative and do not guarantee future success of our clinical trials. Further, we continue to analyze the results of the BX004 Phase Ib/IIa Part 2 clinical trial. And upon further analysis, when we come to conclusions that are different than the ones that are described in this conference call. Except as required by law, we do not undertake to update forward-looking statements. The full safe harbor provisions, 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. Earlier this morning, we announced positive top line results from Part 2 of our Phase Ib/IIa clinical trial evaluating our novel phage product candidate, BX004, for the treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Back in 2023, we announced positive results from the Part 1 of the trial, which showed that treatment with BX004 was safe, well tolerated and resulted in notable reductions in Pseudomonas aeruginosa bacterial burden. Today, we are pleased to report on the positive top line results from Part 2 of the trial, which are comprised of data from a larger number of CF patients dosed for a longer period compared to Part 1. Without question, we are most excited by the positive efficacy signals observed in Part 2, which demonstrate that treatment with BX004 for only a 10-day period in patients with reduced pulmonary function led to clinically meaningful improvement in lung function as demonstrated by both FEV1 and the Cystic Fibrosis Questionnaire-Revised, CFQ-R respirator domain, a patient-reported outcome. In addition, treatment with BX004 achieved a dramatic effect on Pseudomonas aeruginosa culture conversion to negative at the end of treatment in several patients with a long history of Pseudomonas aeruginosa infections. Considering this short treatment period, we are obviously encouraged by these findings and believe that extended treatment with BX004 may lead to a significant improvement in clinical outcomes for this patient population. We are obviously excited by the Part 2 results. For the first time ever in the double-blind, placebo-controlled randomized clinical trial, we demonstrated that treatment with stage therapy, BX004 led to clinical improvement in CF patients chronically infected with Pseudomonas aeruginosa. Considering these results, we plan to advance the BX004 program to a larger pivotal Phase IIb/III trial with the longer duration treatment subject to regulatory feedback and availability of sufficient funding. In the side against antibiotic-resistant infection, we believe that the Part 2 results represent a major milestone for the CF community, phage research and BiomX. Before discussing the Part 2 data in greater detail, I'd like to first provide a brief overview of the significant unmet medical need in CF and the BX004 product profile. Next slide. Chronic Pseudomonas aeruginosa infections are widely recognized as persistent problem due to growing antibiotic resistance, which drives a higher morbidity and mortality in CF. As this chart shows, during infancy and through childhood, these infections can largely be controlled with the use of intermittent antibiotic therapy. Unfortunately, as adolescent patients move into adulthood, the effectiveness of the antibiotic therapy start to decline due to resistance from prolonged and repeated exposure to antibiotics. In addition, patients also developed 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 antibacterial agents. As a result, there is significant unmet need for CF patients suffering from chronic Pseudomonas aeruginosa infections, which is estimated to be approximately 17,000 patients in U.S. and Western Europe alone. Next slide. To address this unmet need, BiomX developed BX004, our proprietary phage cocktail that was designed utilizing our BOLT platform to specifically target chronic Pseudomonas aeruginosa lung infections in CF patients. By taking a cocktail approach in our phage design, BX004 has shown in vitro effectiveness against resistant strains of Pseudomonas aeruginosa bacteria. As a reminder, resistant remains an important issue in this patient population. And due to the cocktail approach in designing BX004 we believe our phage product provides orthogonal coverage across potentially resistant strains of bacteria. In addition, preclinical data has shown that BX004 enables breakdown of the biofilm, which could prove to be a major benefit in helping reduce bacterial burden. BX004 is administered using a nebulizer, 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. Next slide. I'd now like to discuss the Part 2 design of our Phase Ib/IIa trial. The objective of Part 2 of the Phase Ib/IIa were to evaluate the safety and tolerability of BX004 in a large number of CF patients dosed for a longer treatment duration than the Part 1 of the study with the anticipation that the longer treatment might result in greater effects. The primary endpoint was safety and tolerability and exploratory endpoints included decrease in Pseudomonas aeruginosa burden CFU, sputum pharmacokinetics, FEV1 or forced expiratory volume, a Cystic Fibrosis Questionnaire-Revised, CFQ-R, and Cystic Fibrosis Symptom Diary - Chronic Respiratory Infection Symptom Score, or CFRSD-CRISS. The study population was defined as CF patients with a high burden of chronic Pseudomonas aeruginosa infections. Treatment was on top of standard of care antibiotics according to physician's choice. Antibiotic regimen included a continuous regimen defined as taking the same inhaled antibiotic before, during and after study drug, which accounted for approximately 45% of the study participants. And alternating regimen defined is alternating between 2 types of antibiotics every month, which accounted for approximately 25% of study participants or a cycling regimen, which was defined as taking the same antibiotic therapy for 1 month and then discontinuing the treatment for the following months, which accounted for approximately 30% of study participants. Patients received either tobramycin, aztreonam, or colistin, as their inhaled antibiotic during study drug. And there was no restrictions placed on the use of CFTR modulators. While Part 2 of the study was originally designed to include 24 patients, due to better-than-expected recruitment, we ended up recruiting 34 patients. Patients were randomized in a 2:1 ratio, 23 patients receive nebulized BX004 phage therapy and 11 received nebulized placebo, each over a 10-day treatment period, study incorporate subjects on sites in the U.S., Europe and Israel. With that as background, I'd now like to review the highlights from our Part 2 results. Next slide. Beginning with safety, BX004 therapy was well tolerated and no study drug-related serious adverse events or related acute pulmonary exacerbations were observed. Throughout both parts of the Phase Ib/IIa study, BX004 has maintained a clean safety and tolerability profile, leading us to believe that the therapy could be administered over a longer course of treatment to optimize therapeutic effect. With respect to efficacy, patients with reduced lung functions defined as patients with percent predicted FEV1 below 70% showed clinically meaningful improvements in both FEV1 and CFQ-R respiratory domain. As a reminder, FEV1 is an endpoint that measures the volume of air that an individual can exhale doing a forced breath in 1 second in an established marker of cystic fibrosis disease progression. The CFQ-R or Cystic Fibrosis Questionnaire-Revised, is cystic fibrosis specific patient-reported outcome designed to measure the impact on overall patient health, daily live placebo wellbeing and symptoms. The respiratory domain of the questionnaire assesses symptoms of congestion, cough, sputum, wheezing and trouble breathing. BX004 treated patients with reduced lung function had a relative improvement of 5.67% in relative FEV1 and 8.87 points in CFQ-R respiratory domain over the placebo group at day 17, 1 week following end of treatment. The microbiological effect or level of the cure reduction was assessed by two quantitative measurements. First is conversion from a positive to negative sputum culture for Pseudomonas aeruginosa. Here, we observed an impressive effect after only 10 days of treatment in the BX004 arm, 3 out of 21 patients, which is 14.3% converted to sputum culture negative compared to none of the patients in the placebo arm. The second measurement is mean reduction in Pseudomonas aeruginosa, PFU or colony-forming units per gram across the study populations. Here, we observed variable levels in sputum for BX004 versus placebo in the full study population. However, in a prespecified subgroup of patients with standard of care inhaled antibiotics that are in continuous regimen BX004 versus placebo showed a mean bacterial reduction of 2.8 log, which is 99.85% at the end of treatment, exceeding the bacterial reduction showed in Part 1 of the trial. Patients receiving alternating/cycling background antibiotic regimen has showed fluctuation in Pseudomonas aeruginosa level that potentially confound the ability to observe Pseudomonas aeruginosa reduction in this subgroup. During the study period, we also saw no evidence of treatment-related phage-resistant in patients treated with BX004 compared to placebo, which supports the phage cocktail approach used when we design our products. Based on the highly encouraging results on the Part 2 study, we believe this better-than-expected clinical effect over a short 10-day treatment duration derisk our next Phase IIb/III pivotal study if and when we will initiate it. We believe that seeing clinical signals of efficacy after such a short treatment duration increases the chances that treating a larger number of patients for a substantially longer treatment duration could potentially demonstrate a more pronounced clinical effect. We plan on advancing BX004 program into such a trial, subject to regulatory feedback and availability of sufficient funding, and expect to provide more information on timing and study design in the future. Next slide. As mentioned earlier, we are excited to see the positive impact of BX004 on FEV1 and CFQ-R respiratory domain measurements. And this slide highlights these data with BX004 treated patients in blue and placebo in orange. Although the study was not powered to show statistically significant clinical improvement we're pleasantly surprised by the encouraging trends they bring to BX004 treated patients observed in this slide, noting the relatively short treatment duration of 10 days and small sample size. The data shown on this slide are from a subgroup patients with reduced lung function defined as patients with baseline FEV1 levels under 70%. This is prespecified in our statistical analysis and is a common practice in the development of anti-infective and other therapeutics for CF patients in order to avoid a ceiling effect. The graph show differences, which based on literature and discussions with KOLs are clinically meaningful in both FEV1, which is an objective spirometric measurement and CFQ-R, which is a subjective patient-reported outcome. Next slide. On the next slide, we show that treatment with BX004 led to patients converting from a positive to negative bacterial culture. In the BX004 arm, 3 out of 21 patients or 14.3 converted to sputum culture negative to Pseudomonas aeruginosa bacteria after only 10 days of treatment, whereas none of the 10 patients in the placebo arm experienced a conversion. This is a truly remarkable result when one considers the fact that all 3 patients had Pseudomonas aeruginosa lung infections for at least 13 years with 1 patient having Pseudomonas aeruginosa infections for 35 years. In fact, the same patient remained culture negative approximately 2 months after the end of treatment. Interestingly, in Part 1 of the study, 1 subject out of 7 in the BX004 arm, who was precisely positive for Pseudomonas aeruginosa for at least 13 years experienced a 3.3 log reduction at day 15, and later converted to sputum culture negative, which translates to the same 14.3 conversion rate as seen in Part 2 results. Next slide. In this slide, we show the quantified Pseudomonas aeruginosa bacteria levels in sputum. As shown on the chart on the left, for the full study population, the BX004 arm shows a reduction of Pseudomonas aeruginosa bacterial load during treatment of up to 1.6 logs CFU from baseline, which seems to follow the phage treatment rationale. However, we also observed a reduction in the placebo arm, which was not expected. To better understand the effect in the placebo arm, we analyze a prespecified subgroup of patients on continuous antibiotics as standard of care, meaning those using the same inhaled antibiotic prior, during and after treatment period. In this subgroup, there is a much more pronounced effect when comparing the treatment of the placebo arm. The chart on the right shows that this subgroup, those receiving the BX004 therapy experienced a 2.8 log CFU per gram reduction in sputum Pseudomonas aeruginosa levels relative to those patients on placebo. During the treatment period, exceeding results in Part 1 of the trial, which showed an effect size of 1.1 log. Next slide. To further explore this, the next slide shows the difference between patients on continuous antibiotic therapy, the chart on the left and patients taking alternating or cycling antibody therapy as shown in the middle chart. In contrast to the subgroups on continuous antibiotics, the placebo group on alternating recycling antibodies displays a close to 2 log reduction in Pseudomonas aeruginosa levels, likely transient effect due to initiation of a new antibiotic cycle. To better visualize this dynamic, the chart on the right compares the 2 placebo arms, take from the left and middle graphs which shows that the 2 placebo subgroups are distinctly different from each other to the extent that the difference is almost statistically significant during the 10 days of treatment. Hence, we believe that the timing of alternating/cycling antibody regimen maybe confounding the ability to observe CFU reduction in Pseudomonas aeruginosa caused by BX004 in the entire study population. Therefore, a clear phage effect is more clearly observed when background inhaled antibiotics is not changing. Next slide. That concludes our presentation. Considering these promising results, we plan to advance the BX004 program to a larger pivotal Phase IIb/III trial subject to regulatory feedback and availability of sufficient funding. Under this study, we anticipate treating CF patients with BX004 for longer duration, which could potentially demonstrate a more meaningful clinical effect, higher percentage of patients converting from positive to negative Pseudomonas aeruginosa bacterial culture and the more pronounced and sustained overall CFU reduction compared to placebo. With that, we'd be happy to take any questions. Operator?

[Operator Instructions] Our first questions come from the line of Joe Pantginis with H.C. Wainwright.

So first, Jonathan, wanted to ask a very specific question before I get a little bit more macro. With regard to the FEV1, obviously, that's an endpoint that many are looking at, especially in this indication here. Can you just describe the relative difference that you talked about, the 5-point-something different, how this is actually clinically meaningful from a patient perspective.

Sure, Joe. So it is right, this is a relatively objective measurement, FEV1, unlike the CFQ-R, which is patient reported and the patients are basically breathing into device that measures lung capacity. I'm generally perceived as you talk to KOLs and additional -- previous work is that, a 5% relative improvement is considered a clinically meaningful effect. So I think that's where we're aiming. We saw that at day 17. We're seeing that also in day 38. Again, bear in mind, this is, of course, a small cohort. And you remember all our conversations and guidance, we were not expecting any clinical signal whatsoever. We sort of thought this is way too short to see an effect. And of course, the study was not powered. But I think what we're seeing here is signals that look pretty substantial, right? I think that's encouraging. And sort of, hence, to in larger studies, right, we could potentially see the effect earlier than we originally thought.

No, that's great. And I appreciate the reminder there because you certainly did message that in the past multiple times about the short duration. So I think this is definitely promising. So I guess, towards my more macro comments, there is obviously a lot to look at here from the study design. The first part is what are the additional data that you're looking at now when you might be able to share that. And of course, you're being flooded with all these data, do you have any initial thoughts on some of the lessons learned. You touched upon some of them today for the next steps and design with regard to the, say, the cycling timing. Do you have any thoughts right now about the size of the study. Again, this could change tomorrow, and especially what kind of potential duration you might be looking at, or anything else you might want to share for initial thoughts.

Sure. So great question. I think if we take a step back, right, and we just look at the general population, we're seeing these signals and clinical improvement. And I think we're really impressed, and I think we've talked in multiple KOLs, right? I think the bacterial conversion data is dramatic. And that's sort of in the general population. So one can take a step back and say, "Hey, we're seeing a general microbiology effect. We're seeing signals of clinical effect. Let's go for a larger study." It's definitely going to be a longer duration, right? So that's a big difference. We're thinking about order of magnitude of a few months compared to 10 days here for the bigger studies. And I think from previous work that was done by the CF Foundation and others, something like around 110-plus patients is sufficient to pick up a statistical significant difference in a readout such as FEV1, right? So that, I think, some of the guidance that we're taking, as you mentioned, we're still waiting for more data. There's going to be [ 16S ]. We're looking at more information about phage levels that we look forward to sharing with everyone in the future in a conference. So we'll have to take all of that into consideration. But we do think that potentially a longer duration of treatment might address some of the observations that we had on the different antibiotic regimens.

Got it. And then not to nitpick here. It's like with some of the additional data you're looking at, do you feel that any data such as type of background antibiotic type of CFTR modulator might impact the design? Or is that just too much in the weeds at this point?

I would say the majority of patients on this study were on CFTR modulators. So the effect we're seeing is on top of CFTR modulators, which, in our view, makes it even more impressive because remember, some of our conversations, that was also something we're looking into. So far from what we're seeing, we feel fairly confident that the effect is broad and covers patients on different antibiotics and different CFTR. So I think that, of course, we'll need to digest and analyze all the data, but I think that's where we stand right now. And to kind of reiterate, I think as we look at it, right, and say, in 10 days of dosing, we have patients that were infected for many, many years, some of them on very high bacterial load. And after 10 days, we just convert it to 0, right? So that's something when you talk to the microbiology experts, that's not something that happens spontaneously, right? So we're seeing a very strong effect and think that if you dose longer, you probably will increase that effect and get more patients to respond and convert to bacterial count 0.

Our next questions come from the line of Michael Higgins with Ladenburg Thalmann.

Congrats from us as well. Our thoughts and prayers are with you guys considering what's going on over there. Before I get into questions, just to point of comment and [ groove ] your views on dramatic efficacy that we're seeing here. Really impressive stuff. We're looking at that alternating/cycling middle chart, specifically BX004, noticing it doesn't seem to have any effect, which is a bit surprising. Can you help us understand what we might be seeing there?

Michael, thank you for the words of support. We totally agree, right? We don't think that when we're looking at the CFU levels, we're not seeing much of an effect on those patients that are alternating or cycling. I think one of the hypothesis is that when you introduce a new antibiotic. Because one of the things that's happening in the study as we start dosing patients, these guys just went on a new antibiotic. And appears that when you introduce a new antibiotic, it drops the bacterial count dramatically by 2 logs, just on the placebo. So basically, when the phage want to go about their business, there's so much less bacteria and phage sort of praise on other bacteria needs or other bacteria to kind of propagate. So we don't think the phage is finding much with what to interact with, and that's probably limiting dramatically the effect of the phage. So I think one takeaway is that although these patients on average were in many years of antibiotics, there's still sort of changes or these temporal changes in their CFU counts when you introduce a new antibiotic, which is something we need to take into account. Again, we think at this point, we'll get all the data. But as you dose longer, because if you look on the same slide on the chart on the right, we see that there is a big difference on the placebo groups between continuous versus alternating or cycling. But that difference is on the first 10 days, which is exactly when we gave the phage. But later, it kind of stabilized over time. And if you get for a longer time, you should see the effect. Another sort of interesting point, if you go back to our Part 1 study, what we asked for in Part 1 is that the patients will be on a week at a minimum of antibiotics. So we kind of, I think, avoided that dramatic reduction. And then we saw a reduction across all the groups, albeit it was a much smaller number. I think that can address that as well.

That's helpful. Just a follow-up there, and we take a look at the alternating/cycling versus the continuous in your study, it was around 19 and 12, I think have those backwards, but 19 for continuous. From your market research, how does your understanding of the market relate to the enrollment shares that we saw here in this trial, what are you finding for most patients? Are the majority on alternating/cycling versus continuous.

So a lot of that data is not available. There isn't that much. On our study, 45% of patients were on continuous, right? So we are seeing a majority of patients in the study on -- compared to the other group. But again, we think that a longer dosing will probably even out the effect. And bear in mind that when we look at the bacterial conversion data, which we find is one of the most impressive, that's actually on all patient groups, right, on all antibodies. So we think the effect is there across all the patients -- all the different antibiotic regimens. And definitely, as you dose longer, you should see that and see in CFU as well.

And just to clarify, your thoughts going into the Phase III? Do you believe that will be continuous antibiotic patients or will you include the alternating/cycling patients?

We -- early and we need to think and, of course, talk to the agency and consult on all the KOLs and the advisers. But we think there's basis for all comers, and sort of evaluate because there's going to be a major difference when you dose for 3 months compared to just 10 days. So we think it's all comers.

And then lastly, when do you think we'll see the FEV1 data by the background antibiotic regimens?

So this is where the -- we're planning to kind of get all the data as well as some of the questions Joe asked, phage count, et cetera. So I think there's a lot more interesting stuff that we're still kind of going over. And we expect to publish it at a conference in the near term and a publication as well.

I'm showing no further questions in the queue. I'd like to hand the call back over to Jonathan Solomon for any closing remarks.

So thank you again for joining us this morning. We're clearly very pleased with the results of Part 2 of the Phase Ib/IIa study, which we believe provide compelling and confirmatory clinical evidence that BX004 is a highly differentiated and promising therapy with significant potential to address chronic-persistent Pseudomonas aeruginosa infection in patients with cystic fibrosis. I'd like to, first and foremost, thanks to patients and physicians who participate in both parts of this trial. We'd like to thank the Cystic Fibrosis Foundation for their support of our work and valuable advice. I'd also like to thank the entire clinical and R&D team at BiomX who have worked entirely to advance this program and our CRO role, we've been practically part of our team. We're obviously quite excited about these results, and we are now working internally in close consultation with outside regulatory agencies to determine the next steps for the BX004 program. Also, we hope you'll have the opportunity to attend our upcoming virtual KOL event further review the Part 2 data, which is scheduled for December 4 at 12 noon Eastern Time. We'll be joined by 2 highly accomplished KOLs, Professor Eitan Kerem, MD, Professor of Pediatrics and former Chairman of the Department of Pediatrics and Pediatric Pulmonology Unit of the Hadassah University Medical Center in Jerusalem, and former Board member of the European Cystic Fibrosis Society. And Dr. Robert T. Chip Schooley, MD, Distinguish Professor of Medicine, Division of Infectious Disease and Global Public Health and Co-Director center for innovative phage applications and therapeutics at the University of California, San Diego. Thank you again, and have a wonderful day.

This does conclude today's teleconference. We appreciate your participation. You may disconnect at this time. Enjoy the rest of your day.