Entasis Therapeutics Holdings Inc.
Q2 2021 Earnings Call Transcript

Published: 12 Aug 2021

[Operator:]

Good morning, ladies and gentlemen, and welcome to the Entasis Therapeutics' 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.

[Bruce Mackle:]

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 the 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 Investors page at the Entasis Web site. Joining me on today's call from Entasis are Manos Perros, President and Chief Executive Officer; Mike Gutch, Chief Financial Office and Chief Business Officer; and David Altarac, 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.

[Manoussos Perros:]

Thank you, Bruce, and good morning, everyone. Thank you for joining us. On behalf of the management team and all of us Entasis employees, welcome to the inaugural Entasis 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 the 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 ATTACK Phase 3 registrational trial that is evaluating our novel combination Sulbactam-Durlobactam, or SUL-DUR, for the treatment of Acinetobacter infections including multidrug-resistant or MDR strains. As we announced recently, together with our partner, Zai Lab, we completed patient enrollment in July, and expect to release top line data early in the fourth quarter. As a reminder, ATTACK is a Phase 3 registrational trial evaluating the safety and efficacy of SUL-DUR 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 SUL-DUR compared to Colistin in patients with pneumonia and/or bloodstream infections, we have enrolled over 120 evaluable patients, of which approximately one-quarter were enrolled in China. Part B of the trial, which enrolled over 25 patients is a nonrandomized cohort of patients with confirmed Acinetobacter infections that are treated with SUL-DUR, but are not eligible for Part A due to factors that could include colistin resistance, Colistin intolerance or Acinetobacter infection in another body site unresponsive to Colistin therapy. Completion of ATTACK enrollment is a significant milestone for both Entasis and Zai Lab, and we thank the patients, their families, and healthcare professionals for their collective effort that enabled us to complete enrollment during such challenging times. To our knowledge, ATTACK 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 ATTACK trial, we made SUL-DUR available via an expanded access protocol for compassionate use cases in the U.S. One case originating from our program was the subject of a study published recently in Antimicrobial Agents and Chemotherapy, a publication of the American Society of Microbiology. The case study by doctors 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 SUL-DUR plus . 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 SUL-DUR to address a critical unmet medical need. As we would, beyond top line data release and begin our commercialization planning of SUL-DUR and or other programs, we are pleased to welcome Anna Diaz Triola 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're 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 SUL-DUR, later this month, we will be hosting an expert perspectives webinar on Acinetobacter infections. This program will feature presentations by infectious diseases experts, Dr. David van Duin of UNC, Chapel Hill and Dr. Michael Rybak of Wayne State University, who will discuss the burden and current treatment landscape of Acinetobacter infections. We believe to be informative and timely discussion ahead of top line data readout from the ATTACK trial, and are delighted to have such a distinguished experts speaking about the medical needs associated with this multi-drug resistant infection. The program is open to all interested parties and registration details are available on our Web site. 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 3 registrational trial of Zoliflodacin for the treatment of uncomplicated gonorrhea. The trial designed to assess the safety and efficacy of a single oral dose of Zoliflodacin versus the global standard of care, which is a combination of intramuscular Ceftriaxone plus oral Zoliflodacin 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 enrolment 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 Microbe Forum where we presented 11 processes across the portfolio and we're very pleased to be selected for an oral presentation highlighting ETX0462, a novel first-in-class diazabicyclooctane molecule, ETX0462 is our initial product candidate from a non-β-lactam inhibitor of penicillin binding proteins or NBP platform, which we're developing with support from . 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 overcomes the main source of β-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're 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.

[Mike Gutch:]

Thanks, Manoussos. 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. We're finalizing the ATTACK trial, NDA filing preparation, SUL-DUR 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 30, 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 30 2021, compared to $10.2 million for the same period of the prior-year, largely attributable to advancing of SUL-DUR and the ATTACK Phase III trial. Our general and administrative expenses were $3.3 million for the three months ended June 30 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 Manoussos for concluding remarks.

[Manoussos Perros:]

Thank you, Mike. To conclude, we have made exciting progress over the quarter, completing the enrollment in the ATTACK 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 SUL-DUR. And, Alex, we are now ready to take questions.

[Operator:]

Thank you. At this time, we will be conducting a question-and-answer session. Our first question comes from Matthew Luchini with BMO Capital. Please proceed with your question.

[Matthew Luchini:]

Hi, good morning, guys. Thanks for taking the questions, and congrats on fully enrolling ATTACK. So, first on data, obviously we'll be getting the 28-day mortality endpoint and safety, but can you just remind us what other key secondary measures you'll be sharing 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.

[Manoussos Perros:]

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

[David Altarac:]

Yes, 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 showing efficacy. We will have additional 14-day all-cause mortality as well. And we'll have patient demographics, we'll have type of infection, we'll have some sub analysis. 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'll 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 were ineligible for Part A because of colistin resistance. And we will 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 dataset 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.

[Matthew Luchini:]

Okay, great, thank you. And, 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 ELA, what -- or least what key steps remain between top data submission? And then for Anna, I guess the question would be where -- 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 a new launch? Thank you.

[David Altarac:]

Sorry, go ahead, Manos.

[Manoussos Perros:]

Sorry. So, I will ask David to answer your first follow-up question. And just for your information, Anna is unfortunately not participating on 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?

[David Altarac:]

Yes, 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 dataset, 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.

[Manoussos Perros:]

Thanks, David. And Matthew, for your second follow-up question, as we just mentioned, Anna Diaz Triola joined us just a few weeks ago -- a couple of 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.

[Matthew Luchini:]

Okay. Thank you for taking the questions.

[Manoussos Perros:]

Thank you.

[Operator:]

Thank you. Our next question comes from Ed Arce with H.C. Wainwright & Co. Please proceed with your question.

[Ed Arce:]

Great, thanks for taking my questions. And let me add my congrats on the full enrollment of ATTACK. Exciting to see the completion there, and look forward to the top line readouts. A few questions for me, on ATTACK, 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 SUL-DUR. If you could just remind us which of those are in areas where it would be appropriate? And then I have a couple follow-ups.

[Manoussos Perros:]

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

[David Altarac:]

Yes, hi, Ed. Thanks for the question. So, the 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. So, the intent of Part B as I said was to enable the enrollment of patients who have Colistin either resistant or Colistin unresponsive. And so, as a play, evaluating those patients, we design the study with a Part B which was open label, Sulbactam-Durlobactam 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, and clinical outcomes will be included in the overall benefit risk in 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 Sulbactam-Durlobactam. So, to your question, there 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 site, 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 Manoussos 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 I 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 over 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 represent 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.

[Ed Arce:]

Great, that's very helpful. And then a couple of quick follow-ups as well in other areas of your pipeline, firstly, with the GARDP program that you have with your collaborator. I -- if you acknowledged 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 has been any sort of further changes or amendments or any sort of efforts to accelerate that? And then, lastly on your NBP program 462, I recognize that Pseudomonas is the primary target here, but you did also mentioning 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.

[Manoussos Perros:]

Thank you, Ed. And let me take a stab at the second question on ETX0462 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, micro -- Both in the process and the Europe presentation, we did disclose a number of other gram-negative pathogens against, which ETX0462 has good activity, and as well as the number of biothreat pathogens, I can't list them out of the top of my head right now, but there is a number of them, and we have been working with the government agencies to produce the data that have support that statement. We'd be more than happy to follow up with the published information and more detail on the biothreat pathogens. We do believe that, that the data is obviously early days, it's in vitro data and some in vivo work, so far it does support further for the development of ETX0462 both on the gram-negative and on the biothreat side, but it's still a preclinical program, and there is a lot more work to be done before we can talk about the state of work that and other government agencies, who support clinical work would get involved in, but we'd be happy to follow up on the specifics or sustain such as the program moves towards the clinic. And as far as the liquidation, before I turn it over to David, absolutely both GARDP and Entasis we have been working hard to mitigate the delays, which are due to COVID-19. As you recall, the trial had been actually put on hold for about a quarter, but has not resumed enrollment shortly after and multiple new sites have been occupied over the last few months. So, David, if you can provide a little bit more of an update on this, I would appreciate it.

[David Altarac:]

Sure. Thanks, Manoussos. So as Manoussos mentioned, we continue to actively recruit and enroll in our key countries including the U.S., Thailand, South Africa and Netherlands. Some of the stats that we're looking at to mitigate some of the enrollment challenges include opportunities to enhance enrollment within site, and looking at things that we could do to encourage more enrollment again with any 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 opportunities there are based on clear guidances from regulatory agencies. So, from our perspective, as Manoussos mentioned, we're working very closely with GARDP, 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.

[David Altarac:]

[.:]

[Ed Arce:]

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

[Operator:]

Thank you, ladies and gentlemen, we have reached the end of the question-and-answer session. I will now turn the call over to Manoussos Perros for closing remarks.

[Manoussos Perros:]

Thank you, Alex, and thank you all for participating. 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 ATTACK trial enrollment and top line data coming early next quarter, early fourth quarter. We'll look forward to continuing the conversation and to see you on our next quarterly call. Thank you very much.

[Operator:]

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