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00:05 Good morning. My name is April, and I will be your conference operator today. At this time, I would like to welcome everyone to the Lexicon Pharmaceuticals Inc. Fourth Quarter 2021 Earnings Call. Thank you. 0:36 I will now turn the call over to Chas Schultz. Please go ahead, sir..

00:42 Thank you, April. Good morning, and welcome to the Lexicon Pharmaceuticals’ fourth quarter 2021 financial results conference call. Joining me today are Lonnel Coats, Lexicon's Chief Executive Officer; Jeff Wade, Lexicon's President and Chief Financial Officer; and Dr. Craig Granowitz, Lexicon's Senior Vice President and Chief Medical Officer.

01:03 Earlier this morning, Lexicon issued a press release announcing our financial results for the fourth quarter of 2021, which is available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call, along with a slide presentation is available on our website.

01:21 During this call, we will review the information provided in the release, provide a corporate update and then use the remainder of our time to answer your questions.

01:30 Before we begin, let me remind you that we will be making forward-looking statements, including statements relating to the safety, efficacy, and the therapeutic and commercial potential of sotagliflozin, LX9211, and other drug candidates.

01:43 These statements may include characterizations of the expected timing and results of clinical trials of sotagliflozin, LX9211, and other drug candidates; and the regulatory status and market opportunity for those programs.

01:57 This call may also contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, launch and commercialization plans for any approved products, strategic alliances, and intellectual property, as well as other matters that are not historical facts or information.

Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements.

02:22 These risks include uncertainties related to the timing and outcome of our planned NDA submission and resubmission for sotagliflozin in heart failure and our discussions with the FDA regarding sotagliflozin relating to heart failure and type 1 diabetes, the success of our commercialization efforts with respect to any approved products, the timing and results of clinical trials and preclinical studies of sotagliflozin, LX9211, and other drug candidates; our dependence upon strategic alliances and other third-party relationships; our ability to obtain patent protections for our discoveries, limitations imposed by patents owned or controlled by third parties, and the requirements of substantial funding to conduct our research, development, and commercialization activities.

03:09 For a list and a description of the risks and uncertainties that we face, please see the reports we have filed with the Securities and Exchange Commission. I would now like to turn the call over to Lonnel Coats..

03:20 Thank you, Chas. Good morning everyone, and thank you for joining us on the call. I would first like to discuss what is likely on the top of all of your minds and that is our decision to voluntarily withdraw and resubmit our NDA for sotagliflozin. This decision was necessary to ensure the completeness of our NDA submission.

03:39 We recently identified a technical issue with our NDA submission, which was not related to the clinical results or the interpretation of the underlying clinical data. The company identifies supportive documents related to site monitoring visits that were inadvertently not included in the submission.

03:57 We promptly notified the FDA about the issue and have been in discussions with the agency to correct the submission. Unfortunately, the issue was discovered near the end of our 60-day filing review period, which did not allow a sufficient amount of time for us to correct the submission and put the FDA to complete its filing review.

04:17 After consultation with the FDA, we determined that the withdrawal of the NDA in a subsequent resubmission would be the most appropriate action to provide a complete submission for review.

I would like to reiterate that this technical issue does not involve the substance or the analysis of the clinical results and it does not impact the conclusion from our SOLOIST nor SCORED Phase III outcome studies. We plan to correct this issue and promptly resubmit the NDA by early second quarter.

04:47 Now, let me turn our attention to LX9211, which is a selective inhibitor of AAK1. Despite neuropathic pain effecting millions of people, there remains a high level of unmet need for those suffering from the condition.

The current therapies are limited by lack of efficacy, compounded by debilitating side effects and in the case of opioids, risk of potential abuse and addiction.

05:12 We believe LX9211 has the potential to overcome many of the shortcomings of current therapies and become and could become a walk of new innovation for those suffering from Neuropathic pain on a daily basis.

We have made significant progress over the last few months in our two ongoing Phase 2 proof-of-concept studies and expect top-line results in the very near-term. 05:36 For RELIEF-DPN-1, our study and diabetic peripheral neuropathic pain, I’m very pleased to report that we are completing recruitment this week.

We expect to report top-line results by the end of Q2 2022. For RELIEF-PHN-1, our study in post-herpetic neuralgia, which is a global study, we continue to enroll patients and expect to report top-line results in the third quarter of 2022. 06:03 I would now like to invite Jeff, to take us through the financial results for the fourth quarter of 2021..

06:10 Thank you, Lonnel. I will provide some key aspects of our fourth quarter 2021 financials. More financial details can be found in the press release that we issued earlier today and then our upcoming 10-K SEC filing. We ended the year with $86.7 million in cash and investments and no debt.

06:30 While we will require additional capital as we approach the launch of sotagliflozin, we can manage our operations over the next 12-months within our existing capital resources. As indicated in our press release this morning, we had minimal revenues for the fourth quarters of both 2021 and 2020.

06:49 Research and development expenses for the fourth quarter of 2021 increased to $16.5 million from $1 million for the corresponding period in 2020. The R&D expense in the fourth quarter of 2020 reflected a reduction in estimates for external clinical development costs primarily related to sotagliflozin R&D expenses.

07:12 Selling, general, and administrative expenses for the fourth quarter of 2021 increased to $8.8 million from $6.4 million for the same period in 2020, primarily due to higher legal fees.

In total, net loss for the fourth quarter of 2021 was $25.6 million or $0.17 as compared to a net loss of $5.5 million or $0.04 per share in the corresponding period of 2020. 07:40 Our net loss for the fourth quarter of 2021 and 2020 included non-cash stock based compensation expense of $2.2 million and $2.7 million, respectively.

07:51 I would now like to turn the call back to Lonnel..

07:54 Thanks, Jeff Before taking in any questions, let me close out by summarizing our key anticipated milestones and events.

First, let me say the team has been working diligently since discovering the technical issue with our NDA submission and we are working very closely with the FDA to correct issue and promptly resubmit the NDA early in the second quarter.

The resubmission of the NFA will likely result in our planned launch of sotagliflozin and heart failure, if approved occurring in the first half of 2023. 08:24 We are expecting top-line results from our RELIEF-DPN-1 study by the end of Q2 2022. And shortly thereafter, we anticipate the top-line results for RELIEF-DPN-1 in Q3 of 2022.

The news today is certainly disappointing to us, but I want to be clear, this delay does not change the value proposition of sotagliflozin.

08:47 We believe sotagliflozin’s unique dual mechanism of SGLT1 and SGLT2 inhibition provides important and differentiating benefits for patients with heart failure, living with type 2 diabetes, especially those patients with recent and worsening heart failure.

09:02 With that, I'll stop and open the floor for questions and turn it over to the operator..

09:08 And your first question is from Yigal Nochomovitz with Citi..

09:20 Great. Good morning. This is on for Yigal. Thank you for taking our questions. We had one clarification question on the heart failure NDA.

Can you just walk through what needs to be done in order to correct this technical issue and resubmit the NDA?.

09:38 Great question. We've been working with the FDA since notifying them of this matter, and we've already started the process of going back, and putting all of the information that's required to make the application complete.

09:51 So, we know exactly what the issue are, what the issue is, and now we’re starting the work to repair those issues and get this back to the FDA as soon as we can..

10:04 Okay, great. And then where do can you stand with ex-U.S.

Partnership discussions for heart failure? Could you broadly characterize the level of interest you're receiving there?.

10:17 Jeff, you want to talk about that?.

10:19 Yes. We're continuing to have discussions regarding ex-U.S. It is something that I would say is not imminent, but we will continue to have dialogue. We do intend for outside of the U.S. to rely on partnership and collaboration that don't have any ambition of commercializing on our own outside of the U.S..

10:42 Okay. Got it. That's helpful.

And then if I could just ask one more on the pain trials, we're curious if there's any reason mechanistically to believe that LX9211 would be more likely to show a therapeutic effect in PHN or DPNP?.

11:02 Great question.

Craig, you want to take that?.

11:05 Certainly. Thank you, Carly.

As we've shown in a number of publications and discussions, we believe that based on both the knockout mice, the biochemical data that's been done in the animal models that some of the liabilities that are seen in these prior studies of animal models and preclinical development, differentiate potentially LX9211 from a risk benefit standpoint.

Certainly, the liability of addiction potential compared to and some of the other liabilities that are related to gabapentin oxalic acid and tricyclics, we don’t seem to see those in similar animal models.

11:51 Again, I'll hold on the human experience other than what's been published in the rising single and multiple doses, which showed good tolerability in those clinical studies that have been presented publicly..

12:08 And then also, we have very good results in preclinical models for both diabetic peripheral neuropathic pain and post-herpetic neuralgia.

There's more heterogeneity and the population has diabetic peripheral neuropathic pain, which is part of the reason why we did a larger study in that indication, but we have good reason to believe that both of these indications offer a potential for LX9211..

12:36 And I'll speak broadly on the strategy here, is that, the most important trial that we're working on with LX9211 is the diabetic peripheral neuropathic pain study.

The rationale for certainly doing the PHN study given that we did see activity there is important because ultimately you want to get a broad label in the area of peripheral neuropathic pain. 12:57 In order to do that, you're going to have to study then multiple areas where there is neuropathic pain with some level of specificity.

And so, DPN is going to be critical in terms of initial success. Then certainly PHN success will determine just how big the opportunity may be for us in terms of the market size..

13:20 Perfect. Thank you so much..

13:22 You bet..

13:25 Your next question is from Jessica Fye with JPMorgan..

13:30 Good morning, everyone. This is for Jessica Fye. Thanks for taking our question.

A couple of clarifying questions on the technical issue found in the NDA submission, where the site monitoring visits that were not included related to manufacturing, quality analysis, or some other sites?.

13:48 No, these were clinical sites..

13:51 Okay.

And was the visit completed by the FDA, but not recorded in the NDA or was the visit not completed by the agency to begin with?.

14:00 No, these are visits that need to be completed by the sponsor..

14:05 Okay..

14:05 And they exist. We have the source documents; they just didn't make it into the NDA..

14:11 Got it. Okay.

And was there a potential to correct the issue while the NDA was still in submission? Meaning would the FDA have considered correction of the technical issue as a major amendment? Was that the reason why it was pulled?.

14:28 No. You don't amend a filing. I mean, a submission. You can certainly do that on the other side of it, but you don't amend the submission. I think it was a timing issue. We were very, very close to the 60-day date that we had on record and that just was not enough time for the FDA to complete this review nor for us to go back and do the inputs.

So, the best answer was to pull it and get it done and get it back in..

14:57 Okay. Got it..

14:58 One of things I will say, the conversations with the agency was very encouraging because they felt very confident about, I've just characterized the conversations that more of confidence in that the company came forward, and disclosed it and working directly with them on it given that the file was on a review for, excuse me, the submission was on a review for filing.

So, I think my hope is that certainly gained us some goodwill so we can keep moving with the speed that we intend to move with..

15:33 Great. One last question on this issue.

How did you deduct this issue before the FDA?.

15:40 Great question. Prior to any – whenever you make a submission, you pull your team together and you go through all of what you've submitted so you can get ready for FDA inspection, and you make sure there's no gaps in what you've done and you go through that again, and that's how we discovered it..

15:58 Okay, got it.

And a bigger picture, when we think about the shift in timeline for potential NDA resubmission to early 2Q and launch – potential launch in first half 2023, what are some of the considerations to keep in mind regarding cash runway?.

16:17 Jeff, I'll turn that one to you..

16:19 Well, in either of the scenarios we are going to need to be able to bring in additional cash as we get closer to launch. We have the ability to get to manage our operations to get through a year, but we will need additional capital from a cash runway perspective. Other than that, this is really a matter of a delay of a few months.

And that doesn't really change any of the – and as Lonnel said, didn't change the value proposition, didn't change any of the opportunity for the product, it's just a delay..

17:01 Yeah. I think when you do have a delay unfortunately, delay your spending, all of the work that we were doing that start to bring teams on board to get ready for the launch that August delay, which delays out us having to make the spend and therefore allows us to extend our cash runway..

17:21 Got it. Thank you very much for taking our questions..

17:25 You bet..

17:27 Your next question is from Joseph Stringer with Needham..

17:38 Hi, good morning. Thanks for taking our questions. Two quick ones from us.

Just given the slight delay here in the sotagliflozin program, can you just put that into context just given the competitor programs that are out there and, sort of , what does that mean for overall strategy for Lexicon and heart failure, does anything change there? And secondly, on the pain program, would you need to see data from the Phase 2 PHN trial before deciding on next steps for that pain program or would the DPN trial give you, you know if that were positive, could you, sort of proceed into next steps there? Thank you..

18:28 It's a great question. Let me start with the second one first. The DPN study is the most critical study I think for us to make a decision as a go forward. The PHN study is more of a complementary study in terms of our ability to show the drug can be broaden into other areas in neuropathic pain, but we have to have a win on DPN.

18:50 As for your first question, I'm going to turn it over to Jeff..

18:55 This doesn't really change the strategy for us. We anticipated that empagliflozin would get a broader label. We have data that is – and surpassed in the same category in terms of benefit that we saw in the study in heart failure with preserved ejection fraction really across the entire spectrum of left ventricular ejection fraction.

19:20 One of the things that's unique in our program is that we have the SOLOIST study. And it's in recent and worsening heart failure, and it's hard outcomes in that recent and worsening heart failure study.

And that has been one of the areas of focus for our commercialization strategy and that's not going to change and there's really not anything out there that is comparable to that study. 19:46 So, we anticipated that empagliflozin would get a broader label.

It actually is probably a benefit to us because this is going to be the first time that a couple of different drugs including sotagliflozin are going to have the opportunity to be available for patients with – that have been underserved and not well served or maybe not at all served by existing therapies and that's going to be a growing market and we're going to get to leverage that growing market..

20:24 Yes, the other thing that I would just add… Go ahead, Craig. Sorry..

20:29 Yes. One other comment I'd just like to add. I'm sure this is, might be Lonnel’s comment as well as even in the FDA's own press release on empagliflozin, the head of the review division noted that this was not a solution for all heart failure.

And I think that leaves certainly the door open for additional innovation, particularly as Jeff mentioned, what we believe is the incremental value of sotagliflozin across even a broader range of left ventricular ejection fraction, as well as particularly the group of highest risk, which was not specifically covered in the empa, even revised label of recent and worsening heart failure..

21:12 Yes. I think, we'll take this opportunity as we start to rework our resubmission and even strengthen – even more strengthen the focus on what we believe should be a prior review for our application, particularly in a recent and worsening heart failure now that we see the empa data.

21:29 We were more convinced that we have a differentiated compound. So, this could be an opportunity for us to make an even stronger argument. And hopefully, it leads to the outcome that we intend to have once approved, if it should be approved..

21:45 Great. Thanks for taking our questions..

21:50 Your next question is from Julian Harrison with BTIG..

21:55 Hi, good morning. Thank you for taking my questions. You kind of just answered it there. I just wanted to confirm that this need to resubmit the sotagliflozin NDA does not affect potential eligibility for priority review upon acceptance? Thanks..

22:09 Yeah. We have to make the argument. Anytime you submit, you got to make the argument, and I’m sure you will be making the argument in an even stronger way once we resubmit..

22:27 And there are no further questions at this time..

22:34 Well, I want to thank everyone for joining us on the call. There's no greater priority for the organization than to the issue that we identified. We're working very quickly to resolve it. I think we've had very collaborative conversations as I would characterize them with the FDA.

And I think if we are able to move with the speed and the quality that we intend to move with, our objective is to keep moving as fast as we can. And doing that, we’ve outlined that the potential to resubmit will be in the early part of the second quarter.

23:10 And then from there, I think to the point that was just made recently, it really is an opportunity as well for us to make a, given that we've seen what's now been approved for us even make a strong argument for why we think we should have a prior review, particularly for patients with recent and worsening heart failure.

23:29 So, we're going to take this as a slight side back and a delay, but it also could be an opportunity for us to strengthen our application. So, with that being said, I want to thank again for joining us and we look forward to updating you on our next call..

23:45 This concludes today's conference call. Thank you for participating. You may now disconnect..