Zealand Pharma A/S

CSE:ZEAL

Earnings Call Transcript 2022-Q2

[Operator]

Good day, and thank you for standing by. Welcome to the Zealand Pharma Second Quarter 2022 Financial Results Conference Call and Webcast. [Operator Instructions]. Please note that today's conference is being recorded.

I would now like to hand over to your speaker, Anna Krassowska. Please go ahead.

[Anna Krassowska, executive]

Thank you, operator.

Welcome, and thank you for joining us today to discuss Zealand's second quarter results for 2022. I'm Anna Krassowska, Vice President of Investor Relations and Corporate Communications at Zealand. With me today are the following members of Zealand's management team. Adam Steensberg, President and Chief Executive Officer; Matt Dallas, Senior Vice President and Chief Financial Officer; and David Kendall, Chief Medical Officer. You can find the related company announcement and supporting information on our website at zealandpharma.com.

I would like to point out that we will be making forward-looking statements that are subject to risks and uncertainties. These statements are valid only as of today, and the company assumes no obligation to update them, except as required by law. Please refer to recent filings for a more complete picture of risks and other factors.

With that, I will turn the call over to President and CEO, Adam Steensberg. Adam?

[Adam Steensberg, executive]

Thank you, Anna, and thanks to everyone for joining today. Please turn to Slide 3.

This has been a busy quarter for the company, and I'm really happy with the progress we have made on multiple fronts following the announcement of our strategy to prioritize investments into R&D.

In light of these changes, I'm pleased that we completed the sales of V-Go to MannKind in May. For the Zegalogue rescue pen, we are in advanced partner discussions, and I hope to provide an update on this front soon.

In the second quarter, we strengthened our balance sheet. First, by amending the existing note purchase agreement with Oberland Capital, and secondly, by executing a private placement with certain institutional investors. This has extended our cash runway beyond important clinical milestones.

As part of the restructuring activities, we continue to focus on improving our operational effectiveness and implementing corporate cost reductions. Earlier this week, we announced the decision to end the non-liquid ADS program which has been in place since August '17. Today, the American Depositary Shares accounts for less than 1.5% of the total share capital. And by consolidating our listing to NASDAQ Copenhagen, we believe we can maintain trading flexibility for global investors while achieving certain operating efficiencies for the company and reducing costs.

Following those corporate updates, I would like to touch on the clinical pipeline to briefly review some of the progress and upcoming milestones before I turn the call over to David Kendall for additional details and color.

Key priorities are shown on Slide 4. As we give you the pipeline, I want to draw your attention to the revised timelines related to dasiglucagon for Bihormonal Artificial Pancreas system. This is a consequence of focusing our resources as we execute our new strategy and not a reflection of our [ attention ] for the program.

In May, we announced positive results from the Phase III trial of dasiglucagon in infants with congenital hyperinsulinism, or CHI. We are preparing a new drug application or NDA for dasiglucagon, and following our pre-NDA meeting with the FDA, we now anticipate submission in the first quarter of '23.

At the scientific sessions of the American Diabetes Association in June, we presented Phase I data for dapiglutide, our long-acting GLP-1/GLP-2 dual agonist, showing encouraging weight loss in healthy volunteers. This data has given us the confidence to move this molecule forward in obesity, as also announced in June.

In July, we achieved last patient, last visit in EASE SBS 1, our Phase III trial with glepaglutide in short bowel syndrome, and now look forward to seeing the results late in the quarter.

At the upcoming European Association for the Study of Diabetes Annual Meeting in September, our partner, Boehringer Ingelheim, will present Phase II data for glucagon GLP-1 receptor dual agonist in patients with Type 2 diabetes. And finally, we anticipate initial Phase I clinical data from our amylin analog later in the year.

And with that, I will now turn over the call to David Kendall. David was appointed Zealand's Chief Medical Officer in June, and for the past 2 years, he has been serving as a senior global medical adviser to the company. And before joining us, he has held senior leadership positions in clinical and academic medicine and in the biopharmaceutical industry. We're extremely excited to harness his broad experience in diabetes and metabolic diseases that spans more than 35 years. David?

[David Kendall, executive]

Thank you for the kind introduction, Adam.

I would like to begin by discussing the progress with our dasiglucagon program in patients with congenital hyperinsulinism, or CHI, an ultra-rare pediatric disease in which patients suffer from recurrent and persistent hypoglycemia due to excessive insulin production.

On Slide 5, we have summarized key data. As you may recall, we previously reported data showing a clinically meaningful reduction in rates of hypoglycemia measured by continuous glucose monitoring in the Phase III trial in older children when treated with dasiglucagon added to standard of care, shown in the left-hand panel.

In May, we announced positive top line results from the Phase III trial in 12 infants up to 12 months of age with CHI who required continuous intravenous glucose support to prevent or manage hypoglycemia. The focus of this trial was to evaluate the ability of dasiglucagon treatment to reduce and eventually remove the need for continuous IV glucose infusion. The trial met its primary endpoint, demonstrating that dasiglucagon, delivered as a continuous subcutaneous infusion via pump, resulted in a statistically significant and clinically meaningful reduction in the requirement for IV glucose when compared to placebo.

Numerically, dasiglucagon treatment reduced the mean glucose infusion rate to 4.3 milligrams per kilogram per minute compared with 9.5 milligrams per kilogram per minute with placebo, a treatment difference of 5.2 milligrams per kilogram per minute, which is a 55% reduction in the requirement for glucose by IV infusion. It is also worth noting that 11 out of the 12 patients participating in the trial subsequently enrolled into the ongoing long-term safety extension study.

We look forward to presenting the full trial results of Study 103 at the European Society for Paediatric Endocrinology or ESPE Annual Meeting in mid-September.

We anticipate the data from this Phase III trial, along with data from the previous Phase III trial in older children as well as the information derived from the safety extension trial, will form the basis of an NDA for dasiglucagon in CHI, and we expect to submit in the first quarter of 2023. We had previously projected the submission in late 2022. However, as the NDA preparation is now underway, the revised timeline reflects the comprehensive analysis for individual patient outcomes that we believe are essential for our submission, which we further believe will ensure as complete a data set as possible for our NDA targeting this ultra-rare disease.

Turning to Slide 6. Our full pipeline is shown here, and I will highlight a few of our programs.

First, I would like to share an update on another of our dasiglucagon projects, namely, the bihormonal artificial pancreas program, which as many of you know, is being performed in collaboration with Beta Bionics. We have recently aligned with our partners on a sequential approach for the Phase III pivotal program. The Phase III program now consists of 3 sub trials designed to support the marketing application for the Bihormonal iLet Bionic Pancreas, known as the iLet Duo, and an NDA for the use of dasiglucagon in bihormonal artificial pancreas systems for the treatment of Type 1 diabetes.

Our 2 companies have agreed that the smaller crossover study of 60 patients to assess safety and efficacy of the Bihormonal iLet Duo and insulin-only configuration, known as the iLet, will now be completed prior to initiating the 2 larger randomized controlled Phase III trials, which will include 350 adults and 350 pediatric participants. Importantly, the sequential approach allows for an initial assessment of clinical outcomes from the shorter-term comparative trial prior to initiation of the main pivotal trials. The clinical protocols are being updated accordingly, and we expect Beta Bionics to initiate the small crossover trial in early 2023. We believe this sequential approach will allow us to optimize Phase III execution and use our resources most effectively.

Moving on to glepaglutide, our long-acting GLP-2 analog being investigated for the potential treatment of short bowel syndrome. The pivotal Phase III EASE-1 study is designed to allow us to demonstrate a significant reduction in the need for parenteral support for people living with SBS. A once or twice weekly fixed dose injection of glepaglutide, delivered by a ready-to-use auto injector, can provide clear and very important features of differentiation from the currently-approved product.

We are excited to report that we have recently achieved last patient, last visit in the Phase III EASE-1 trial, and our expectation is to have top line results available by the end of September or early October of this year. Pending review of these data, we anticipate that this randomized controlled trial will serve as the basis for our planned NDA for glepaglutide.

Moving to a discussion of our work in obesity, we believe we have a number of novel and exciting assets in our current portfolio, and we are pleased to be advancing this clinical portfolio, including our GLP-1/GLP-2 dual agonist, our novel long-acting amylin analog, and the dual glucagon GLP-1 receptor agonist, all assets generated from our peptide platform.

Initial data from the clinical studies of our GLP-1/GLP-2 dual agonist, dapiglutide, reported at this year's American Diabetes Association Scientific Sessions, demonstrated a weight loss of up to 4.3% from baseline after only 4 weeks of treatment in a Phase I trial of healthy volunteers. Our novel long-acting amylin analog is currently under study in Phase I clinical trials, and we expect data from the Phase I single ascending dose trial by the end of 2022.

This amylin asset is differentiated by virtue of design characteristics that both allows for once-weekly dosing and for formulation and co-formulation with other peptides in the physiologic pH range, a feature that should facilitate the potential for development of combination therapies.

Additionally, initial data readouts from the Phase II program for the long-acting dual glucagon receptor GLP-1 receptor agonist, also known as BI 456906, being developed with Boehringer Ingelheim, will be disclosed later this year. Initial data from the Phase II trial in Type 2 diabetes is scheduled for presentation at the European Association for the Study of Diabetes in September highlighting the primary endpoint of the trial, the dose relationship of treatment on hemoglobin A1c from baseline to 16 weeks relative to placebo. Along with our BI colleagues, we also anticipate presentation of the secondary endpoints of the Type 2 diabetes trial, assessing the effect of change on body weight at a scientific congress later in 2022.

In summary, it has been an incredibly active, exciting and data-rich time for our clinical development programs, and the second half of the year looks to maintain the strong momentum across our entire research and development platform.

Now, I will turn the call over to our CFO, Matt Dallas, to walk us through our half year financial results. Matt?

[Matthew Dallas, executive]

Thanks, David.

In the first half of 2022, we initiated our organizational restructuring, taking steps to strengthen our financial future and ensuring that Zealand can continue to discover and develop innovative new peptide therapeutics.

In addition to the 90% workforce reduction implemented in the United States, in the second quarter, we amended our loan agreement with Oberland Capital and raised DKK 274.8 million in a direct private placement. With these events and the consolidation of the exchange listings as mentioned at the beginning of the call by Adam, the company is well positioned to execute on its strategy.

On Slide 7, you will see Zealand's income statement for the first 6 months of 2022 and how it compares to 2021. Total revenue for the first 6 months was DKK 43.5 million or USD 6.1 million. This was driven by net Zegalogue product revenue and partnership revenue from our collaboration with Alexion. The operating result for the period was a loss of DKK 539.2 million or USD 75.3 million.

Sales and marketing costs were mainly related to the commercial infrastructure in the U.S. to support Zegalogue while R&D costs mainly -- primarily related to our late-stage clinical programs.

As a result of our announced restructuring, all gross margin and operating expenses related to V-Go are accounted for as discontinued operations. Total discontinued operations for the first half of 2022 were a loss of DKK 97.9 million or USD 13.7 million.

Slide 8 illustrates our financial position and ability to support our growing business through continued investments. Total operating expense for the period was DKK 577.4 million or USD 80.6 million. Included in the operating expenses for the period are DKK 75.8 million related to our announced restructuring. And cash on hand at the end of June 2022 was DKK 864.4 million or USD 120.7 million.

Turning to our financial guidance on Slide 9. The company anticipates that net product revenue from the sales of the Zegalogue is expected to be DKK 11.5 million, plus or minus 10%. This is a reduction of DKK 7.5 million from our updated guidance issued on May 12. With the completion of the asset purchase agreement for V-Go with MannKind Corporation, the company will no longer provide guidance on net product revenue associated with sales from that program.

Zealand Pharma expects revenue from existing license agreements. However, since such revenue is uncertain in terms of size and timing, we do not intend to provide guidance on such revenue.

Net operating expenses in 2022 are expected to be DKK 1 billion, plus or minus 10%. This is unchanged from our prior guidance, and is a decrease of DKK 200 million from the original guidance issued on March 10.

With that, I will now turn the call back to Adam.

[Adam Steensberg, executive]

Thank you, Matt.

As previously announced, Matt, he will be leaving Zealand by the end of August, and this will be his last quarterly call. I would therefore like to thank Matt for his leadership and many contributions over the last few years, and I wish him all the best with his next challenges.

In light of Matt's departure, we have been conducting a search for a new CFO for the company, and we expect to be able to make an announcement soon.

Turning to Slide 10. The second quarter has delivered on several fronts, and we believe Zealand is now well positioned to leverage the value of our pipeline. We have some exciting months ahead of us with significant number of important milestones, which should further clarify the potential of our many new product opportunities.

Thank you all. I will now turn it over to the operator for questions.

[Operator]

[Operator Instructions] We are going to proceed with the first question. The first question comes from the line of Joseph Stringer from Needham & Company.

[Joseph Stringer, analyst]

Heading into the SBS readout here, can you provide your thoughts just based on feedback from physicians, which efficacy endpoint is most important for potential widespread adoption or uptake in the SBS market? For example, from a registrational perspective, obviously, your primary endpoint is absolute changing PS. Gattex was approved on a -- in part on a different endpoint, the responder analysis greater than 20% PS reduction. But are there other key end points such as number of patients completely weaned off PS or change in other PS metrics that you would consider important from a potential commercial perspective?

[David Kendall, executive]

Yes. This is David Kendall. Thanks for the question.

And you very nicely summarized both what was part of the previous regulatory approval for teduglutide. And given the construct of our trials, obviously, the statistical power for registration is tied to a reduction in volume of parenteral support.

And secondarily, looking at a similar proportion reduction in that parenteral support, but I think you also make a very important distinction, which is the potential to reduce the number of days on parenteral support, discontinuing parenteral support, either on a given day or a series of days, will be critically important.

Obviously, powering the study for regulatory review based on the latter has its challenges, given that this is a rare disease, and having adequate numbers of subjects to demonstrate that with clarity or certainty could be challenging. However, we will be collecting just that in our clinical program to assess whether there are meaningful reductions in the days off of parenteral support.

So I think all 3 go well beyond just achieving a regulatory endpoint and are critically important, both to the burden of SBS, and ultimately, to the significant burden of days on parenteral support.

[Operator]

We are going to proceed with the next question. The next question comes from the line of Lucy Codrington from Jefferies.

[Lucy-Emma Codrington-Bartlett, analyst]

I've got a few.

Just still on the glepaglutide Phase III and the expectations going into the data. So just in terms of setting our expectations, should we be looking at the kind of 1.6 to 2-liter reductions in parenteral nutrition volumes seen with Gattex in their Phase III and the 30% to 40% placebo-adjusted response rates are sensible bars for efficacy?

And then related to that, can you remind us of any stratification by remnant bowel anatomy in your trial? Does that differ to that used in the Gattex Phase III, and could that have any influence when we're looking at the data sets together with the caveats of cross-trial comparisons, of course? And are there any other differences between the Phase IIIs that we should be aware of?

And I'll stop at this and jump back in the queue.

[David Kendall, executive]

Very good. If I can test my short-term memory and recall those.

I think your first question to the proportional response, if you will, in reduction of parenteral support. We know that glepaglutide, glepa, is a GLP-2 agonist just like teduglutide. So while these are not comparative studies, obviously, this is placebo-controlled, we would estimate that at least qualitatively, reductions that have been seen with the other GLP-2 receptor agonist would be those that we would expect. But obviously, to go further and try to predict at this point what those data may show would be both premature and speculative only. I think that is a reasonable starting point, certainly.

And I think I wrote it down, but I've already lost the second half of that question.

[Lucy-Emma Codrington-Bartlett, analyst]

Just whether there was any stratification by anatomy?

[David Kendall, executive]

Yes. So we do have so-called CIC or colon-in-continuity subjects as well as stoma patients within the trial. But there is no a priori at least primary endpoint for assessing differences. But obviously, this will be a part of the secondary analyses that we will undertake. Obviously, understanding that those 2 populations can behave differently, particularly when it comes to completely withdrawing parenteral support.

So yes, that will be part of our analysis. It is not obviously part of the primary endpoint.

[Lucy-Emma Codrington-Bartlett, analyst]

And so just to be clear on the differences between those, you would expect those with continuity to respond less. Is that right?

[David Kendall, executive]

Yes, correct.

[Lucy-Emma Codrington-Bartlett, analyst]

Okay. Great.

And then just my last question just relates to the dapiglutide obesity trial. I believe, from reading the press release, that it's going to be an investigator-sponsored study. Does that just reflect resource prioritization rather than you conducting the trials yourself?

[David Kendall, executive]

I think it is not solely a resource utilization question. Obviously, there will be more than just efficacy endpoints and opportunity to explore mechanistic components of how the compound acts, which are obviously done most effectively in a well-established academic center, which does a trial looking at complex mechanistic responses to the incretin hormones.

So I think beyond some efficiencies of being able to initiate this earlier for a relatively more efficient cost in the setting of an investigator-led trial, it will also allow for that detailed look at potential mechanisms which may be at play for this very novel agent.

[Lucy-Emma Codrington-Bartlett, analyst]

Okay. Very helpful.

[Operator]

[Operator Instructions] We have the next question coming from the line of Mike Novod from Nordea.

[Michael Novod, analyst]

It's Michael Novod from Nordea. So 3 questions.

First of all, to the BI 45 compound, the GLP-1 glucagon coagonist. So I could see that the abstract is already titled in the abstract book, so maybe just to sort of gauge your confidence in the safety, because we have had a lot of discussions around glucagon safety. We've seen a publication by Novo with their glucagon compound [ GLP-1 ] glucagon, which didn't sort of look too promising in terms of safety. So just gauging your confidence on the safety side, going into the EASD? I know you can't comment on the specific data.

Then secondly, on Zegalogue, maybe, Adam, you can give a bit of extra color on the potential timing of a license deal for this asset?

And then lastly, also in respect to glepaglutide, how should we think about timing with regards to also a license deal on this, given that you are sort of progressing, if that is positive, towards submitting an NDA? I guess, a potential partner would like to be active on that side as well? Or how do you think about timing for glepa should data be positive?

[David Kendall, executive]

This is David. I'll start with the BI 456906 question and the safety profile.

Obviously, Phase II is really the first more comprehensive look at efficacy and safety. And I think as you suggested, having the posted abstract for the BI compound is both exciting for us, and we look forward to seeing the full details of the glycemic outcomes at EASD. And I think it would be premature to further speculate on behalf of our BI partners on the comprehensive safety, but obviously, we fully expect that tolerability and safety will be detailed in that presentation.

But given that we've now completed that Phase II in the Type 2 population suggests that at least completion of the trial supports its utility. To go beyond that, I think I'd be getting ahead of the formal presentation and speculating on the safety outcomes.

[Adam Steensberg, executive]

Yes.

And Michael, maybe also just to follow up on David's note here, which I completely agree with. I think at the American Diabetes Association meeting in June, BI did show some more details on the molecule, including the ratio of glucagon and GLP-1 and so on. I think you should be careful to compare across these molecules even though they are named glucagon or glucagon GLP-1 there could be different ratios and they're quite individual observations for each molecule. So I would also ask you to draw the attention to the presentation that BI made at the American Diabetes Association Meeting.

Then for Zegalogue, as I said, we are in advanced discussions. And I've said all the time that it's our ambition to complete a deal before we leave this quarter, and this is still the ambition for the company. And I think it's premature to comment more on this until we can announce something hopefully.

On the last one, for glepaglutide, we now -- really, the key focus for us is to get to the key results and then engage with FDA. And on the partnering front, our key focus right now is to complete our discussions on Zegalogue. And then we also have CHI, as you know, coming up. So it's not that we are in a hurry. We think we have our plans in a good place. And -- but -- as I've also shared in prior calls, we have had quite a significant inbound interest in the program. So we will kind of take it from there, but we will not advance these discussions until we have seen results for sure.

[Operator]

We are going to proceed with the next question. The next question has come from the line of Thomas Bowers from Danske Bank.

[Thomas Bowers, analyst]

Yes. A couple of questions from my side here.

So can you maybe just give us a little bit of color on the US delisting. So in terms of annual cost savings, so including fees and insurance and legal stuff? So that was the first question.

So just -- then just a follow-up on Zegalogue, can you maybe just remind us on the commercial commitments you have here now going into August? So is there anything that makes things a little bit more difficult for you? And also in addition to that, the recent [indiscernible] infusion. So I'm just wondering whether you are maybe looking more into sort of an out-license with royalties compared to sort of a one-time upfront payment from just selling the asset?

And then my last question, just on BI 45. Just wondering in regards to -- of course, we are all awaiting the Phase II, but I mean Boehringer, private company, they could also make a decision prior to those Phase II data and then go into -- or announce Phase III. So I'm just wondering if whether you have any information, or maybe even could potentially see Boehringer take that decision prior to the Phase II data, if that's possible?

[Adam Steensberg, executive]

So maybe I will address the Zegalogue and BI, and then turn over the ADR question to Matt on the potential cost savings.

But if we take BI, of course, you can say we would expect BI to inform us when they take that decision, and we will probably also inform the market if the decision will be taken on the initiation of Phase III. And we cannot comment further on when they will take this decision right now, if they will do it before or after, they have also seen the Phase II data from the obesity study. I remind you that it's a Type 2 diabetes study that is being presented at the EASD and also later this year. So -- but we do expect them to see the full data from the obesity study as well.

So this is really up for BI to decide, and then we will, of course, inform accordingly.

For Zegalogue, I really can only -- you can say confirm that we are in advanced discussions. We are keeping the product on the market. We are supporting the product from all the regulatory, medical and supply aspects. We have very little sales support, as you can also see from the numbers now. So that has been -- that -- so it's completely in line with restructuring that we announced. And that's, of course, also why we have a key focus on completing a potential agreement before we leave the quarter. So -- and I can honestly not -- I will not comment more on the deals, potential deal structures [indiscernible] at this time.

Matt, maybe over to you on the ADR, potential cost savings and...

[Matthew Dallas, executive]

Right. Yes. We have not publicly stated what our exact expectations are on a per dollar basis, but I can tell you that the cost of maintaining the U.S. listing requires significant external legal and audit requirements due to the regulatory reasons. As well as significant internal time, cost and efforts in finance, legal, risk management.

As this delisting takes place and occurs, we will see significant costs reduced from those areas as well as, again, from internal kind of focus as well.

[Operator]

We are going to proceed with the next question. The next question comes from the line of Lucy Codrington from Jefferies.

[Lucy-Emma Codrington-Bartlett, analyst]

Apologies.

Just, if I may, is it possible to get an updated cash runway guidance now following the delisting and the debt restructure and the capital raise? And then in terms of potential near-term milestones that are not included in guidance, is there anything that we should be aware of that could be a possible near-term milestone?

[Adam Steensberg, executive]

Matt, will you start on this one?

[Matthew Dallas, executive]

Yes.

So right now, the current cash runway, and this is based on just as the company stands at this very moment, takes us into Q2 of 2023. This does not include potential Zegalogue partnerships. It does not include any future milestones such as from our partnerships with BI or Alexion, or any additional partnership cost savings from any of the other additional programs with obesity and SBS. It also includes the full burden of maintaining the delisting. The delisting has not been yet completed.

So as we move into the next period and the updated guidance on that side, all of those costs will be filtered through and will be reflected in future announcements.

[Operator]

We have no further questions at this time. I will now hand back the call to Mr. Adam Steensberg, CEO for closing remarks. Please go ahead.

[Adam Steensberg, executive]

Okay.

With that, we would like to thank you all for attending and for your questions. We look very much forward to connecting on future announcement and updates. Have a good day.

[Operator]

This concludes today's conference call. Thank you for participating. You may now disconnect your lines.