DURECT Corporation

Ladies and gentlemen, welcome to the Direct Corporation Second Quarter 2024 Earnings Conference Call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star and zero on your telephone keypad. As a reminder, this conference has been recorded. I will now turn the call over to Tim Papp. Thank you. You may begin.

Good afternoon, and welcome to Direct Corporation's second quarter 2024 earnings conference call. This is Tim Papp, Chief Financial Officer of Direct. Before we begin, I would like to remind you of our safe harbor statement. During the course of this call, we may make forward-looking statements regarding Direct's products and development, expected product benefits, our development plans, future clinical trials, or projected financial results. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Further information regarding these and other risks can be found in our SEC filings, including our 10-K and 10-Qs under the heading Risk Factors. To begin, I would like to review our second quarter 2024 financial results. Total revenues in the second quarter of 2024 were $2.2 million compared to $2.1 million in 2023. 2024 revenues were slightly higher due to a small increase in revenue from collaborations. R&D expense was $2.2 million in the second quarter of 2024 compared to $7.9 million for the prior year. The decrease was primarily due to lower clinical trial related expenses, facility and lower employee related costs. SG&A expenses were $3 million in the first quarter of 2024 compared to $3.8 million for the prior year. The decrease was primarily due to lower employee facility market research and professional services expenses. As of June 30th, we had cash in investments of $15.8 million, and our cash burn for the second quarter was $5.8 million. We believe our cash on hand is sufficient to fund operations through the end of 2024. Now, I would like to turn the call over to Jim for a business update.

Thank you, Tim. Hello, everyone. Thank you for joining us today. I'm excited to share an update on our progress towards initiating our confirmatory phase three clinical trial for larsucosterol and alcohol-associated hepatitis. As I mentioned on previous calls, we have been in discussions with the FDA about our proposed clinical trial design, and I'm happy to say that the dialogue with the agency has been positive. The FDA has confirmed that a single pivotal trial would be sufficient to support an NDA filing in AH. They also clearly recognize the unmet need in AH and the strong results of Lercicosterol in our Phase IIb trial affirmed. Both doses of Lercicosterol in affirmed reduced mortality by nearly 60% in the U.S. patients, who represented 76% of the total number of patients in the trial. As a result of the affirmed data, we were granted breakthrough therapy designation for Lercicosterol in May. Breakthrough therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically meaningful endpoint. Breakthrough status allows us to have more intensive interaction with the FDA, including senior managers, throughout the development process. Under this distinctive designation, in July, we had a very productive and positive Type B meeting with the FDA to discuss our trial design. In fact, this meeting was the most productive interaction I've had with the FDA in my 30-plus year career in drug development. We are awaiting the written minutes from this meeting and look forward to sharing more details about our proposed protocol in the near future once we receive those minutes. In the meantime, I can share a bit more about the expected timeline for conducting our Phase III trial. We've already undertaken significant action to prepare to initiate the trial. And subject to obtaining adequate funding, we are preparing to start the trial before the end of the year. We expect this would enable us to report top-line data from our Phase III trial in the second half of 2026. Our ultimate design for the trial will be based on the strong clinical data we generated in Affirm and feedback from our discussions with the FDA. We have submitted a number of abstracts for posters and a presentation for the AASLD meeting this fall. We look forward to sharing additional data analyses and the details of the protocol in an update after we've received the written minutes from our in-person Type B meeting. We're also excited that the affirmed data was presented for the first time at an oral late-breaker presentation at the EASL conference in June. We remain encouraged by the positive reception from hepatology thought leaders and key opinion leaders for the affirmed results and their continuing support for Leucicosterol's potential to provide a clinically meaningful survival benefit and AH patients. As a brief reminder, Affirmed was a placebo-controlled, double-blind, multinational study with two active dosing arms of 30 mg and 90 mg of garcicosterol and a placebo arm of approximately 100 patients each. In total, we randomized 307 patients with severe AH from a global network of clinical sites. Our sites included renowned liver centers in the United States, Australia, the EU, and the UK. and we had the honor of working with some of the world's preeminent thought leaders in AH. The top-line results in the key secondary endpoint of mortality at 90 days showed a 41% reduction with a 30 mg dose of leucocosterol and a 35% reduction with a 90 mg dose of leucocosterol as compared with placebo. Even more impressive results were observed in the U.S. population, which comprised three-quarters of the total enrollment in the firm. That was 232 out of the 307 patients. In the U.S. patients, we saw reductions in the 99 mortality of 57% and 58% for the 30 and 90 milligram ARBs, respectively, as compared with placebo. Although not part of the original trial statistical analysis plan, the p-values for these results were both approximately 0.01. Very importantly, our suco-sterile exhibited an excellent safety profile with no serious adverse events in either arm and greater than 20% reductions in the number of treatment emergent adverse events for both active arms when compared with a placebo group in these severely ill patients. Ultimately, these clinically meaningful reductions in mortality, coupled with the reduction in adverse events in these severely ill patients, reinforce the compelling risk-reward proposition of leucicosterol. We continue to believe that the affirmed data provide compelling evidence that leucicosterol could represent a safe and effective therapy with life-saving potential for AH patients. There are no approved therapies for AH today. Therefore, if farcicosterol meets our expectations in Phase III and we gain approval, it would likely be the first FDA-approved treatment for this disease and establish a new standard of care. AH is the cause of more than 160,000 hospitalizations each year in the U.S., and with a 90-day mortality rate of approximately 30%, is responsible for tens of thousands of deaths each year. In addition to this high mortality rate, AH represents a significant cost to the U.S. healthcare system. Hospitalizations attributed to AH incur charges of $67,000 to $180,000 per patient, a total charge to hospitals of approximately $10 billion annually. As a result, Larcico-Stero represents a potential blockbuster opportunity in the U.S. alone that could simultaneously provide overall cost savings to the healthcare system. With that, we'd now like to take any questions you might have.

Thank you. Ladies and gentlemen, we will now be conducting a question and answer session. If you would like to ask a question, please press star and 1 on a telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star and 2 if you would 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. Ladies and gentlemen, we will wait for a moment while we poll for questions. The first question comes from Francois Brissebois with Oppenheimer. Please go ahead.

Hi. Thanks for taking the questions. I was just wondering, you gave us a little bit of guidance in terms of timelines to start the trial. Is it fair to assume that the next kind of update to the investing community would be around the meeting minutes? And in general, if the meeting was in July, how long does it usually take to get the minutes back and then potentially disclose, you know, whatever you can disclose from that? Thank you.

Yeah, sure. Hi, Frank. Yeah, we're still waiting to hear back. The meeting was held January. fairly recently, actually, near the end of July. And typically it's four plus weeks before you get those back, and we'll be able to give an update at that point in time. We feel pretty comfortable about the timeline because we've got a good handle on the powering of the trial and the like, but we just want to get confirmation from the agency before we discuss that further.

Understood. And then have you seen or have you disclosed any of the maybe differences that you saw between the EU and US sites in the trial? There's such a difference probably in terms of the data. What have you disclosed publicly there? And maybe just remind us of how this works. How does the patient come in when he's severe and how much time do you have to treat him? Just any color there that might explain the difference between the EU and the US would be helpful. Thank you.

Yeah, we'll definitely provide more color on that as the year unfolds. We have some potential posters and presentations coming up on that. And Weiqi is here with me, so maybe, Weiqi, you can briefly describe the patient's experience when they come in.

Well, we actually pre-screened thousands of patients and then screened basically over 300 or something. patients and then finally enrolled 307 patients.

And there definitely were differences around the world regionally. We know just, for example, in the Franco-Belgian region, they would only dose on Mondays because they didn't want to have their employees, their study coordinators and like coming in over the weekend and drawing blood. And they also required biopsies first, which took four to seven days. So if that patient didn't get the results back on a Monday, they had to wait until the next Monday. So certainly the patient journeys and experiences were different. And even at times, not just the presentation, but anyway, there certainly are some regional differences that we will share going forward. And those absolutely, in my mind, explain why we're seeing the differences that we do. But nonetheless, the drug looks very good.

Yes.

more data will be okay yeah yeah yeah yeah but look for AASLD okay perfect and um sorry can you remind us where AASLD is this year and maybe on that note has has there so we talked about the sites but has there been an analysis or if you can't share you can't share yet but has there been any more color on that impact of the endpoint of being, you know, mortality or transplant, liver transplant?

Yeah, there certainly is. I mean, transplant is not going to be a major factor for this disease simply because there aren't enough livers to go around. I mean, that's kind of the end result of it. And also, transplant is administered based on many different factors, a number of which are actually socioeconomic. it's, you know, if you're at a regional hospital with a certain insurance level, your odds of getting a transplant are zero, basically. And if you're at one of these tertiary centers in, say, your area in Boston or out here at UCSF or Stanford, you're in a very different circumstance if you've got the insurance and the potential for transplant goes way up. That being said, there are 160,000 hospitalizations per year for this disease, and there are only about 8,500 liver transplants conducted in the U.S. A quarter or so of those go to these patients. So only about 2,000 or so livers are available to, you know, well north of 130 or so thousand patients. And so, you know, 98% of these patients will never see an opportunity at a liver transplant. So at the end of the day, it really comes down to mortality, and that's been our focus. And the agency understands that as well. So, you know, we're feeling pretty good about the opportunity going forward for the phase three.

Okay, great. I can quickly Google this, but where is ASOD this year?

Oh, sorry. It's in San Diego. So, yeah. 15th to the 19th of November. And so this one's going to be easier for us than for you, Frank.

Thank you. All right. Thank you very much, guys. Look forward to the update.

All right. Thanks. Thank you. The next question is from Ed Arcee with HC Wainwright. Please go ahead.

Hey, Jim. Thanks for taking my questions. Sure. Congrats on the progress and especially the breakthrough therapy designation. Yeah. Yeah, just had a couple questions around your upcoming meeting minutes. I know that's important to get it straight documented. What further details that you're withholding now could we expect to be announced once you've had a chance to review those meeting minutes? In particular, I'm wondering about the confirmation around the primary endpoint, the powering of the trial, and perhaps the number of patients.

Yeah, I think it'll be those kind of things. You know, obviously, you have to wait until the minutes come back to get to be able to finalize it. But that's the type of thing one's looking for. And I do think we are very fortunate to have the breakthrough designation. And it's also, I think, very impressive. You know, we all know that this drug missed its primary endpoint, but showed a dramatic reduction in mortality. not only globally, but also in particular in the U.S. And the agency recognized that and granted us breakthrough, which, as I said in my talk, I mean, it's wonderful to be able to have, you know, face-to-face meetings again, to be able to sit down with them and have open conversations. They've got highly experienced hepatologists on their team who are very aware of of the impact and the fact there's really nothing to help their patients out there, and they see this as an opportunity. So they're very excited about that. They're not excited, I guess. They're very encouraged and working with us on the potential for this drug. Okay.

I know we've had discussions around the endpoint before, especially the differences between the U.S. and ex-U.S., Is it your intention for the phase three to be only 90-day mortality at the primary?

I want to wait for the minutes to finalize that conversation. But certainly, as I was suggesting with the prior, you know, questions, we have learned a lot about this disease. And I think ours was, I would say, the most comprehensive controlled study done on this disease in many, many years. And so we really did understand a lot more now about how to construct this trial and how to conduct it and the type of patients to enroll, when to enroll patients and the like. And so I'm extremely confident personally that this trial has a very good chance of success.

Okay, maybe just a couple final questions then from me. First, is it your intention, again, given the results and the bifurcation from a firm, is it your intention to conduct a phase three only in U.S. sites? And then what is the overall cost that you expect for the phase three trial?

Yeah, I think right now we are comfortable to say that we're looking at the U.S. right now. It's not that we don't believe it's a great opportunity outside the U.S., but it is. I think it's just simpler. We know that there's continuity in the U.S. healthcare system and the diagnosis of these patients and the presentation of these patients, all of those things. And we're treating the U.S. patients first. I mean, our average age in the United States for these patients was 44 years old. And we had about almost a 28% mortality in these patients. And we're talking You know, 28% out of 160,000 hospitalizations die at average age of 44. That's more people that die in automobile accidents. That's in the same range as die from breast cancer, only 20 years younger. It's a horrible circumstance for us, and it is different outside the U.S., so that's absolutely the case. As far as the cost, I'll let Tim speak to that. Go ahead, Tim.

Yeah, Ed. The expected outside costs for the trial are around $25 million. And then we'll also have to fund the G&A to operate the company alongside that. If you look at our most recent quarter, we reported a burn of about 5.8 million. 2.1 of that was debt service. So that leaves between three, about three and a half, four million of G&A. We think that can come down or be roughly consistent from where it is. So that kind of gives you a sense of how much we're expecting the total spend to be over the life of the trial, which we expect to report data in second half of 26.

Great. Thanks so much.

Thank you. The next question is from Carl Burns with Northland Capital Markets. Please go ahead.

Thanks for the question and congratulations on your progress. Most of my questions have been answered, but I'm wondering what guidance, if any, you might be able to give us on the third and fourth quarter, second half of the year in terms of OPEX. Thanks.

Yeah, Tim. Yeah, Carl, it's Tim.

So second half of the year, again, they think we would expect our operating expenses to be roughly the same in that kind of three and a half, four million a quarter range. and that's before we pay down the Oxford term loan. No reason to expect that goes up significantly. The majority of the incremental expense in the phase three will be external costs. We feel like we have the appropriate staffing to conduct the phase three.

Got it. Great. Thank you.

Thank you. We have a follow-up question from Francois Chris Boyce with OpenIMA, please go ahead.

Hi, Tim, can you just quickly remind us of the terms on that Oxford loan?

Yeah, it's a straightforward term loan. We make monthly amortization payment of about $720,000. It's interest bearing at low team's interest rate. The final payment date is September of 2025. And there is a $2 million final payment as well.

Thank you. Thank you.

As there are no further questions, I would now like to hand the conference over to Jim Brown for closing remarks.

With that, we'd like to thank you for your time today. And as always, if you have any follow-up questions, please feel free to reach out to us here and we look forward to talking to you. Thank you and take care.

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.