Entasis Therapeutics Holdings Inc.

Good morning, ladies and gentlemen, and welcome to the Entisys Therapeutic Second Quarter Results Conference Call. Currently, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. As a reminder, this conference call is being recorded. I will now turn the call over to Bruce Mackle, Managing Director with LifeSci Advisors. Please go ahead, sir.

Thank you, Alex. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ from statements made on this call is contained in our periodic reports filed with the SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise the forward-looking statements. Information presented on this call is contained in the press release we issued yesterday and in our Form 10-Q, which may be accessed from the investor's page of the Entesys website. Joining me on today's call from Entesys are Manos Peros, President and Chief Executive Officer, Mike Gutsch, Chief Financial Officer and Chief Business Officer and David Alterac, Chief Medical Officer. Manos will provide a summary of the company's progress during the quarter and recent weeks before turning it over to Mike for a review of the company's financial results. Following their prepared remarks, the management team will be available for your questions. I will now turn the call over to Manos.

Thank you, Bruce, and good morning, everyone. Thank you for joining us. On behalf of the management team and all of us Entesys employees, welcome to the inaugural Entesys quarterly results call. As the company progresses toward commercial stage, it is our intention to formalize our investor outreach and provide regular opportunities for interactive dialogue. We appreciate your attendance today and look forward to our discussion on this and future quarterly calls. Yesterday, after market close, we issued a press release outlining our second quarter financial results, as well as the progress made advancing our pipeline. I'll spend just a few brief moments summarizing these developments before turning the call over to Mike for a review of our financials. Then we will be happy to take your questions. I'll begin with our ATT&CK Phase 3 Registrational Trial that is evaluating our novel combination, Solbactam-Durlobactam, or SOLDOR, for the treatment of Acinetobacter infections, including multidrug-resistant or MDR strains. As we announced recently, together with our partner, Zylab, we completed patient enrollment in July and expect to release top-line data early in the fourth quarter. As a reminder, ATT&CK is a Phase III registrational trial evaluating the safety and efficacy of Sodor in patients with confirmed carbapenem-resistant Acinetobacter infections. In total, we have enrolled over 200 patients in the trial. In part A, which evaluates the efficacy of Soldor compared to Colistin in patients with pneumonia and or bloodstream infections, we have enrolled over 120 valuable patients, of which approximately one quarter were enrolled in China. Part B of the trial, which enrolled over 25 patients, is a non-randomized cohort of patients with confirmed Acinetobacter infections that are treated with Soldor but are not eligible for Part A due to factors that could include colistin resistance, colistin intolerance, or a sematobacter infection in another body site unresponsive to colistin therapy. Completion of ATT&CK enrollment is a significant milestone for both Entesys and XyLab, and we thank the patients, their families, and healthcare professionals for the collective effort that enabled us to complete enrollment during such challenging times. To our knowledge, ATT&CK is the largest antibiotic-resistant pathogen-specific registrational trial to be conducted globally, and the first to focus specifically on carbapenem-resistant acinetobacter infections. We look forward to announcing top-line data in the coming months. Concurrent with the ATT&CK trial, we made SOLDOR available via an expanded access protocol from compassionate use cases in the U.S. One case originating from our AAP program was the subject of a study published recently in Antimicrobial Agents in Chemotherapy, a publication of the American Society of Microbiology. The case study by Dr. Zaidan, Hornak, and Reynoso of the University of Texas Medical Branch in Galveston, Texas, highlighted the problem of a critically ill patient due to COVID-19 respiratory failure who developed extremely drug-resistant Acinetobacter baumannii pneumonia and septic shock. the patient received a combination cocktail of antibiotics, culminating in 14 days of Soldor plus cefiderocol. Despite a very poor prognosis, the patient significantly improved on therapy, recovering well enough to eventually be discharged and return home. We believe this case highlights both the growing threat of antimicrobial drug resistance, as well as the potential of Soldor to address a critical unmet medical need. As we look beyond top-line data release and begin our commercialization planning for solar and our other programs, we are pleased to welcome Anna D'Astriola as our new Chief Commercial Officer. Anna comes to us from Summit Therapeutics, where she was instrumental in developing the commercial strategy for the company's first product against C. difficile infections. Prior to Summit, Anna held commercial leadership roles at Flexion Therapeutics, Chiasma, Cubist, and Biogen. With her track record of commercializing products across multiple therapeutic areas, including antibacterials, we are delighted to welcome her to our leadership team and look forward to working with her to build the commercialization capabilities which will complement our R&D platform. Completing our update on Soldor, Later this month, we will be hosting an expert perspectives webinar on Acimetobacter infections. This program will feature presentations by infectious diseases experts, Dr. David Van Duyn of UNC Chapel Hill and Dr. Michael Rybak of Wayne State University, who will discuss the burden and current treatment landscape of Acimetobacter infections. We believe this will be an informative and timely discussion ahead of a top-line data readout from the ATT&CK trial and are delighted to have such distinguished experts speaking about the medical need associated with this multidrug-resistant infection. The program is open to all interested parties, and registration details are available on our website. Turning now to the next candidate in our portfolio, we continue to support the Global Antibiotic Research and Development Partnership, or GARDP, and the Phase III Registrational Trial of Soliflodacin, for the treatment of uncomplicated gonorrhea. The trial, designed to assess the safety and efficacy of a single oral dose of zoliflodacin versus a global standard of care, which is a combination of intramuscular subtraction plus oral azithromycin, is actively enrolling patients with uncomplicated gonorrhea, including infections potentially caused by multidrug-resistant strains of Neisseria gonorrhea. Our partner of the program, GARDP, has now activated clinical trial sites in the U.S., the Netherlands, Thailand, and South Africa. Unfortunately, due to ongoing challenges with the pace of patient enrollment related to the ongoing COVID-19 pandemic, we remain unable to provide guidance for completion of the trial at this time. We will provide enrollment updates and guidance for completion of the trial when appropriate. Finally, we also continue to make progress with our early portfolio programs. Last month, we participated in the World Micro Forum, where we presented 11 posters across the portfolio, and we're very pleased to be selected for an oral presentation highlighting ETX0462, a novel, first-in-class diazobisaclo-octanone molecule. ETX0462 is our initial product candidate from a non-beta-lactam inhibitor of penicillin-binding proteins, or NBP platform, which we're developing with support from CARB-X. We believe NBPs constitute a potential new class of gram-negative antibacterial agents that are designed to target a broad spectrum of multidrug resistant bacterial pathogens that overcome the main source of beta-lactam resistance, which is driven by beta-lactamases. We selected ETX0462 as our initial candidate, given its antimicrobial activity against multiple gram-negative pathogens, including Pseudomonas aeruginosa, as well as a number of high priority biothreat pathogens. We are currently working to complete the required preclinical activities to advance ETX0462 into the clinic and look forward to updating you all on the progress of this exciting program. With that, I will now turn it over to Mike for a review of our financial results and other business developments.

Thanks, Manos. During our second quarter, And as previously announced in June, we strengthened our balance sheet by finalizing a private placement agreement with a subsidiary of Innoviva Inc., our largest shareholder, which provided net proceeds to the company of approximately $20 million. We intend to use the proceeds from this transaction for finalizing the ATT&CK trial, NDA filing preparation, sold or launch readiness, as well as working capital and other general corporate purposes. We reported a net loss of $12 million for the three months ended June 30th, 2021, compared to a net loss of $13.4 million for the same period in the prior year. The decrease in net loss was primarily related to an increase in grant income during the second quarter of 2021 versus the prior year. Research and development expenses were $10 million during the three months ended June 30th, 2021, compared to 10.2 million for the same period of the prior year, largely attributable to advancement of SOL-DOOR and the ATT&CK phase three trial. Our general and administrative expenses were 3.3 million for the three months ended June 30th, 2021, compared to 3.2 million for the same period of the prior year. As of June 30, 2021, cash and cash equivalents were $56.4 million compared to $53.2 million as of December 31, 2020. Based on our current operating plan, we believe that our existing cash and cash equivalents, including amounts received from the most recent private offering, will be sufficient to fund our operating expense requirements through the second quarter of 2022. With that, I'll turn it back over to Nanos for concluding remarks.

Thank you, Mike. To conclude, we have made exciting progress over the quarter, completing enrollment in the ATT&CK trial with top-line data expected early in the fourth quarter and significantly advancing our pipeline. With the additional financing now secured, we look forward to preparing for NDA submission and launch readiness of SOLDIER. And Alex, we are now ready to take questions.

Thank you. At this time, we'll be conducting a question and answer session. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from Matthew Lucchini with BMO Capital. Please proceed with your question.

Hi, good morning, guys. Thanks for taking the questions and congrats on fully enrolling ATT&CK. So first, on data, obviously we'll be getting the 28-day mortality on point and safety, but can you just remind us what other key secondary measures you'll be sharing and that you would want us to particularly be focused on when that initial data comes out? And then I have a follow-up from there.

Hey, good morning, Matthew, and thank you for the question. I will ask Dr. David Zaltrek to answer this.

Yeah, hi, Matthew. Thanks for the question. So, the top-line data will reflect, as you noted, the primary efficacy endpoint, which is the 28-day all-cause mortality, and also the data around the primary safety endpoint, which is nephrotoxicity per the RIFLE score. When we announce top-line data, we'll have some other endpoints. Some of them were key secondary endpoints, including clinical outcome, which is an important outcome for the purposes of, you know, showing efficacy. We will have additional 14-day all-cause mortality as well. And we'll have patient demographics, We'll have type of infections. We'll have some sub-analyses. And then on the safety side, we'll be looking, as I mentioned, on the rifle score for nephrotoxicity, but we'll also be looking at treatment emergent adverse events in a side-by-side comparison. And we will also be looking at drug-related safety endpoints in a side-by-side comparison. You're also aware that we have a Part B in the study. And Part B, as Manos mentioned, is the open label arm for patients who are ineligible for Part A because of colistin resistance. And we will be presenting both 28-day, 14-day all-cause mortality in Part B, as well as safety from that arm as well. And then top line data will obviously be followed up with a complete data set that is included in the study. And those endpoints are all documented in the clinical trials posting as well as other public statements that we've made. But it'll be a continuation of some sub-analyses that we've had from our top line data.

Okay, great. Thank you. And how, I guess, are you prepared to make any, two sort of related questions here. Are you prepared to provide any color on timing of regulatory filing post-BLA? Or at least what key steps remain between top-line data and submission? And then for Anna, I guess the question would be, Can you provide a little bit more color on where you stand from a pre-commercial perspective and what are the key next steps ahead of any launch? Thank you.

So I will ask David to answer your first follow-up question. And just for your information, Anna is unfortunately not participating in the call today, but after David has finished his answer, I will cover some of the initial thoughts that we have on pre-commercialization. David?

Yeah, so as you all know, after top line data is presented, there will be a series of additional steps that we'll need to take. As I mentioned a moment ago, we'll have to review the entire data set, which will follow. Upon the full assessment of the complete data, we plan to have a hopefully pre-NDA meeting. We will certainly have a meeting with the FDA. We hope that it's a pre-NDA meeting. And based on the outcome of that meeting, that would determine timing around any regulatory filing in the United States. But the major next step after top line data is full data analysis and then a discussion with the FDA on filing plans.

Thanks, David. And Matthew, for your second follow-up question, as you, as we just mentioned, Anna D'Astriola joined us just a few weeks ago, a couple weeks ago, and has started, obviously, engaging with us on preparing for commercialization readiness. We have done a lot of work ahead of data, but ultimately the launch and strategy will be determined by the data we get at the end of Phase 3. With just a few weeks now to go to the early part of fourth quarter, we'll be able to provide you a more fulsome picture of that side of what we're working on at the next call.

Okay. Thank you for taking the questions.

Thank you. As a reminder, if you'd like to ask a question, please press star 1 on your telephone keypad. Our next question comes from Ed Arce with HC Wayne Writing Company. Please proceed with your question.

Great. Thanks for taking my questions, and let me add my congrats on the full enrollment of ATT&CK. Exciting to see the completion there and look forward to the top-line readout. A few questions for me. On ATT&CK, a couple questions. First, on the open label Part B portion of the study, and you mentioned you enrolled over 25 patients in that. Just wondering, how will this fit in the overall NDA, and is there any potential here for inclusion of those types of patients in the label? And then a related question you mentioned in addition that there are certain criteria around appropriate body sites for solder. If you could just remind us which of those are and areas where it would be appropriate. And then I have a couple follow-ups.

Thank you, Ed, and good morning. Thank you for the questions. I think that's another one for Dr. David Altrecht, Part B and body size. David? Yeah.

Hi, Ed. Thanks for the question. So, Part B is a critical part of the study. It is part of the overall study, and the data from Part B will be included in the application. The intent of Part B, as I said, was to enable the enrollment of patients who had colistin either resistant or colistin unresponsive. And so as a way of evaluating those patients, we designed the study with a Part B, which was open-label sulbactam, drilobactam, plus imipenem. Patients from Part B, any efficacy data from Part B, as agreed to with regulatory agencies, will reflect descriptive efficacy. They will not be included in the primary efficacy analysis. But any data from that, including, as I mentioned, the 28-day or 14-day all-cause mortality data and clinical outcomes will be included in the overall benefit, risk, and totality of data from a descriptive standpoint. But Part B patients will be included in the overall safety database. So they are part of the overall safety database given that they have been exposed to and received subactam, duralobactam. So to your question, they will be a critical part of the NDA. representing supportive and descriptive efficacy and as part of the primary safety database. With respect to body sites, the patients enrolled in Part A were required to have either a hospital-acquired bacterial pneumonia, ventilator-associated pneumonia, or bloodstream infection However, in Part B, as Manos mentioned, those patients who had colistin-resistant Acinetobacter infections from any body site, if they met all of the other eligibility requirements, were able to be enrolled in Part B. And so data from that will be generated from the Part B of the trial. With respect to your question about labeling, Clearly, it's a little premature to comment on what kind of labeling we might get, but actually, my background is actually significantly in the regulatory space, and I've had a lot of experience in product labeling, and I would think that given the design of the trial, given that all of these were pre-specified and agreed to and clinically relevant endpoints, that we would push strongly to include that descriptive information in the product labeling. Whether regulatory agencies would agree remains to be seen. But clearly, the data represents the totality of the data, and from our perspective, would be meaningful for prescribers. So we would obviously plan to have that in product labeling. But ultimately, that will be based on the regulatory assessment by regulatory agencies.

Great, that's very helpful. And then a couple of quick follow-ups as well in other areas of your pipeline. Firstly, with the GARP program that you have with your collaborator, I acknowledge that you cannot really give an update just yet on the enrollment completion. But just wondering if you could share with us at least qualitatively any sort of sense for progress there and sort of thinking about ultimately getting the study completed if there's been any sort of further changes or amendments or any sort of efforts to accelerate that. And then lastly, on your NPV program 462, I recognize that Pseudomonas is the primary target here, but you did also mention a couple or a number of high-priority biothreat pathogens. And so I'm wondering if you might be able to disclose which of those in particular that you're focusing on and if there is any potential opportunity here, ultimately, to work with BARDA for those threats. Thanks so much.

Thank you, Ed. And let me take a stab at the second question on ETX-0462 first, and I will then turn it over to David to give you a qualitative update on the progress for Zoliflodacin and the course of the trial there. So, for ETX0462, as you rightly pointed out, the focus is on drug-resistant pseudomonas. In our presentations at MICROBE, both the posters and the oral presentation, we did disclose a number of other gram-negative pathogens against which ETX0462 has good activity. and as well as the number of biofeed pathogens. I can't list them off the top of my head right now, but there's a number of them. And we have been working with government agencies to produce the data that support that statement. We'd be more than happy to follow up with the published information and more detail on the biofuel pathogens. We do believe that the data is obviously early days. It's in vitro data and some in vivo work. So far, it does support further development of ETX0462, both on the gram-negative phosphatidylsidamona side and on the biofuel side. But it's still a preclinical program, and there is a lot more work to be done before we can talk about the stage of work that BARDA and other government agencies who support clinical work would get involved in. But we'd be happy to follow up on the specifics and also stay in touch as the program moves towards the clinic. And as for Zoliflodacin, Before I turn it over to David, absolutely, both GARDP and ETHESYS, we have been working hard to mitigate the delays, which are due to COVID-19. As you recall, that trial had been actually put on hold for about a quarter. but has resumed enrollment shortly after, and multiple new sites have been activated over the last few months. So, David, if you can provide a little bit more of an update on this, I would appreciate it.

Sure.

Sure.

Thanks, Manos. So, as Manos mentioned, we continue to actively recruit and enroll in our key countries, including the U.S., Thailand, South Africa, and Netherlands. Some of the steps that we're looking at are, to mitigate some of the enrollment challenges include opportunities to enhance enrollment within sites and looking at things that we could do to encourage more enrollment, again, within each site. We're looking within countries for opportunities to potentially open other sites. And then we're also looking at opportunities potentially to move into other geographies if there are opportunities there. So we're looking at it from a very clinical operations micro standpoint as well as a macro standpoint in terms of site related mitigations as well as overall study enrollment mitigations. With respect to your question on any sort of future plans, we continue to look at how COVID-19 has impacted enrollment in the study, focusing on much of what the FDA has published in their guidance on their perspective of how COVID has impacted clinical trials and working off of that and ensuring that we have a well-designed study. We will continue to look at opportunities, again, on what sort of what sort of opportunities there are based on clear guidances from regulatory agencies. So from our perspective, as Manos mentioned, we're working very closely with Guard P. We're looking at mitigations at all levels, and we'll continue to look at opportunities to enhance enrollment and do that within the regulatory guidances that we've received from regulatory agencies.

Ed, if I may follow up on your specific question for 0462, again, I have a number of biofeed pathogens that you asked. So it is a very broad spectrum of activity, as I mentioned, including Bacillus anthracis, Yersinia pestis, Francisella tolarensis, a number of brucal dairy species, including Pseudomalae. So very, very broad biofuel potential coverage. But once again, ETX0462, still preclinical, early days and doing all the work as fast as we can with support from CARB-X to move these toward the clinic.

Thank you both. That's very, very helpful.

Thank you. Ladies and gentlemen, we have reached the end of the question and answer session. I will now turn the call over to Manos Paros for closing remarks.

Thank you, Alex, and thank you all for participating. We have, as we mentioned earlier, as we summarized today, we've had an exciting quarter with new financing available, progress across the pipeline, and, of course, the completion of the ATT&CK trial enrollment and top-line data coming early next quarter, early fourth quarter. We look forward to continuing the conversation and to see you on our next quarterly call. Thank you very much.

This concludes today's conference, and you may disconnect your lines at this time. Thank you for your participation, and have a wonderful day.