Williams Companies Q1 2024 Earnings Call Transcript

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Provided by Quartr
May 9, 2024

There are 16 speakers on the call.

Operator

Welcome to the Kinetics Pharmaceuticals First Quarter 2024 Earnings Conference Call. At this time, all participants are in listen only mode. Following management's prepared remarks, we will hold a question and answer session. I will now turn the call over to Corey Davis of LifeSci Advisors. Please go ahead.

Speaker 1

Thank you, Alan. Hello, everyone, and welcome to Krenetic's earnings call. Joining me today are Doctor. Scott Struthers, Founder and Chief Executive Officer Doctor. Alan Krasner, Chief Endocrinologist and Mark Wilson, Chief Financial Officer.

Speaker 1

Also joining us for the Q and A portion of the call are Doctor. Dana Pizzuti, Chief Medical and Development Officer and Jim Hassard, Chief Commercial Officer. The press release announcing the Q1 2024 financial results was issued today and is also available on the Cornedyx corporate website. As a reminder, we'll be making forward looking statements and I invite you to learn about the risks and uncertainties associated with these statements as disclosed in our SEC filings. Such forward looking statements are not a guarantee of performance and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's businesses.

Speaker 1

These forward looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases and Coronetic's SEC filings, including its Annual Report on Form 10 ks. I'd also like to specify that the content of this conference call contains time sensitive information that is accurate only as of the date of this live broadcast, May 9, 2024. CorMedix takes no obligation to revise or update any forward looking statements to reflect events or circumstances after the date of this conference call. With that, I'll hand it over to Scott. Go ahead.

Speaker 2

Thank you, Corey. Good afternoon, everyone, and thank you for joining us on our Q1 2024 results call. I'll begin by spending a few moments summarizing our recent accomplishments before turning the call over to Doctor. Alan Krasner, our Chief Endocrinologist. He will discuss our clinical programs and recently reported data in more detail.

Speaker 2

Kinetics had an extremely strong start to 2024. Recently, we reported positive results from 2 late stage clinical studies for paltucitin in patients with acromegaly and carcinoid syndrome. Behind paltucitin, we've built a remarkably deep pipeline. This includes our 2nd internally discovered clinical stage compound CRM-four thousand eight hundred and ninety four, which will now be known as atumelanab. At the ENDO conference this June in Boston, we will present 5 abstracts from our clinical development programs, including 4 late breaking abstracts.

Speaker 2

2 poster presentations will highlight initial data in each of the ongoing open label Phase 2 studies evaluating the safety and efficacy of etumelnat in patients with CAH and Cushing's disease. We are also hosting an in person reception to review data from clinical studies of etomelnet in CAH and ACTH dependent Cushing's syndrome at 6 p. M. On Monday, June 3rd for those attending in person. Data from the entire PATHFINDER Phase 3 acromegaly program will be featured in a science and innovation theater led by Doctor.

Speaker 2

Kevin Yuan of the Barrow Neurological Institute on Saturday, June 1st. Three posters from the paltucitine acromegaly clinical program will also be presented highlighting results from PATHFINDER 2, the use of acromegaly symptom diary in PATHFINDER 1 and updates on the long term safety and efficacy data from the ongoing open label extension study. We've also made excellent progress towards new development candidates this quarter in all of our early stage programs. These include a PTH receptor antagonist for the treatment of hyperparathyroidism, a TSH antagonist for the treatment of Graves' disease, including thyroid eye disease and our programs for diabetes and obesity. Now let me take a few minutes to dive a little deeper into the progress made with the 2 paltucitin indications.

Speaker 2

We're extremely pleased to have completed our Phase 3 program in acromegaly with a successful readout of PATHFINDER 2 in April. This study evaluated paltucitin in people with acromegaly who are not pharmacologically treated and was the second of 2 pivotal trials. PATHFINDER 2 achieved its primary endpoint of IGF control and met all secondary endpoints with high levels of statistical significance. Together with the Pathfinder 1 results we reported last year, we now have data from 2 Phase 3 studies to support an NDA filing for the treatment of acromegaly in the second half of this year. In anticipation of a potential 2025 launch of paltucitin, we're continuing to work on important aspects of commercial readiness.

Speaker 2

We've already held multiple advisory boards and conducted market research with physicians to gather their input on how to optimize the communication of the paltucitin program. We will continue to educate the medical community with data presentations at multiple medical conferences in the coming months. We'll launch a campaign later this year directed towards healthcare providers to increase awareness of the unmet needs with the current standard of care, including injection site pain, breakthrough symptoms and the months long regimens required to identify the appropriate dosage for their patients receiving injectable depots. An accompanying campaign directed at patients will be launched early next year. Our market access team has also been active dialogue with leading payers to understand the current marketplace and the dynamics for paltucitin to become a valuable treatment option for patients if approved.

Speaker 2

PATHFINDER 1 data has already been well received and we are seeing a similarly enthusiastic response to our early conversations regarding Pathfinder 2. We're also very pleased with the results from the open label Phase 2 study in carcinoid syndrome patients that's demonstrated meaningful reductions of both frequency and severity of flushing episodes and bowel movements caused by this disease. These effects were rapid, sustained and consistent with the preliminary data we reported last December. Overall, we believe the safety and efficacy profile of paltucitin in this study supports progressing into a Phase 3 study as soon as we can. We plan to discuss these results with the FDA and align on a Phase 3 study design, which enable us to begin a Phase 3 study by the end of the year.

Speaker 2

Finally, we strengthened our balance sheet with a $350,000,000 private placement in February from new and existing equity investors. This additional capital has provided us with sufficient runway to fund operations into 2028 based on current projections for our pipeline of product candidates. In summary, looking to the rest of 2024 2025, we anticipate multiple upcoming milestones from our clinical candidates and continued advancement of our deep pipeline of emerging candidates that address increasingly higher prevalence indications. As has been our practice since inception, we continue to invest in our world class discovery capabilities that provide the roots for our long term success. With that, I'll hand it over to Doctor.

Speaker 2

Alan Krasner, our Chief Endocrinologist to talk about our clinical programs.

Speaker 3

Thank you, Scott. Today, I will provide updates on recently reported clinical programs starting with paltucitin. As a reminder, the Phase 3 PATHFINDER program was designed to evaluate the safety and efficacy of paltucitin for the treatment of a broad spectrum of patients with acromegaly. Both PATHFINDER studies met all pre specified primary and secondary efficacy endpoints and paltucitine was shown to be generally well tolerated. We therefore intend to seek approval for patients who might switch from injected SRLs to paltucitine as studied in PATHFINDER 1 and also in those who are not currently treated with medications and might start paltucitin as a first line treatment as studied in PATHFINDER II.

Speaker 3

We reported most recently the top line results from the untreated patients in PATHFINDER 2. Besides meeting all key endpoints, it was notable that IGF-one was reduced from elevated baselines in 93% of patients treated with caltusitine. These IGF-one declines occurred rapidly with most of the effect occurring in just 2 to 4 weeks. These reductions were durably sustained throughout the treatment period. Significant improvements in acromegaly symptom control associated with paltucitin compared to placebo have now been documented in 2 major independent controlled trials.

Speaker 3

As previously discussed, we are very excited to further explore our rich database into which patients reported their symptoms on a daily basis during the trials. With the database from PATHFINDER 1, we have already been able to perform additional interesting analyses, which we will be reporting at the Endocrine Society meeting in June. We have wondered for a long time whether daily oral paltucitin might result in a difference in the frequency of day to day symptom exacerbations that plague many patients with acromegaly treated with long acting injections, and we look forward to reporting on this soon at the meeting. We will also be presenting late breaking updated data from our long term open label extension cohort from the Phase 2 ACROBAT ADVANCE study. A number of the participants in this study have now been treated with paltucitine for over 4 years.

Speaker 3

The overall data set suggests that paltucitin represents a lot more than just a user friendly convenient oral substitute for an injection. Unlike the current first line agents, caltusitine has been rigorously demonstrated to control symptoms of acromegaly as well as biochemical markers of disease activity. The notably rapid IGF-one response observed in PATHFINDER 2 could allow patients and physicians to reach the fully effective dose of paltucitin much faster than is the case for the current standard of care. A simple once daily oral agent could prevent the pitfalls, pain and unneeded expense associated with the current standard of care. People already dealing with the burdens of acromegaly might not need to schedule their lives around the next injection and dealing with the side effects that often occur after these injections.

Speaker 3

With caltucitin, one would not need to worry if the last injection was administered correctly and whether or not it will last until the next one is due nor would one need special equipment or to take a course on how to self administer acromegaly medication at home. In short, paltucitine may represent a completely new paradigm for somatostatin receptor based therapy. Paltucitin's 2nd target indication, carcinoid syndrome, has also shown promising results. In March, we reported top line results from the open label Phase 2 trial. This study enrolled participants with carcinoid syndrome who experienced 1 or both of the key symptoms of the disease, diarrhea and flushing.

Speaker 3

Participants were either naive to standard of care treatment or untreated and actively symptomatic or were controlled on SRL therapy and willing to wash out prior to entry. Caltucitine was generally well tolerated at the doses evaluated in this trial with no severe or serious treatment related adverse events. In addition, pharmacokinetics in this patient population was consistent with what we expected to see from prior experience. We observed significant and meaningful reductions in both and severity of bowel movements and flushing episodes, consistent with the initial results we reported last December. Importantly, the intensity of these symptoms was also reduced by paltucitin.

Speaker 3

These reductions occurred quite rapidly and were sustained throughout the 8 week treatment period. We intend to discuss the Phase 2 carcinoid syndrome data with the FDA to align on a Phase 3 study design. We look forward to updating you on the Phase 3 details, including dose, registrational endpoint and timing once we've had these discussions. As Scott discussed, our second investigational compound in clinical development is aptumelnet, which is a once daily oral ACTH receptor antagonist in development for the treatment of both congenital adrenal hyperplasia or CAH and Cushing's disease. The adrenal glands are the sole source of excessive steroid that cause the clinical complications in both disease states and this steroid production is driven by excessive exposure to ACTH.

Speaker 3

It is natural therefore to target the ACTH or MC2 receptor in order to fundamentally interrupt the pathologic progression of these diseases. That is because the receptor is the sole mediator of ACTH signaling and it is found only in the adrenals. The lead indication for attumelnet is classic CAH, a genetic disorder that affects approximately 27,000 patients in the U. S. These patients lack a critical enzyme in the adrenals responsible for cortisol production.

Speaker 3

The hypothalamus and pituitary responds to these low cortisol levels by producing high levels of ACTH. This excess ACTH in turn causes over stimulation of the adrenal cortex, resulting in overproduction of cortisol precursors like 17 hydroxyprogesterone and adrenal androgens like androstenedione also known as A 4. The adrenal hyperandrogenemia causes many serious medical complications beginning in utero progressing through childhood and into adulthood. Because CAH patients cannot produce cortisol, exogenous glucocorticoid replacement is required for life, but replacement doses should be very low and these low doses should not cause adverse effects. As a result, many physicians find it necessary to use high supraphysiologic doses of glucocorticoids in an attempt to suppress elevated ACTH levels and thereby lower adrenal androgen production.

Speaker 3

These elevated glucocorticoid doses are frequently associated with adverse effects such as weight gain, elevated glucose, edema, bone loss and a host of other serious medical problems. It is very difficult to find a dose of glucocorticoid, which effectively controls adrenal androgen production without causing these side effects. This highlights the fundamental challenge in treating this disease to strike the right balance between reducing adrenal androgens yet minimizing the effects of excess glucocorticoids. We believe etumelimant is the right approach to achieve this balance and look forward to showing initial data from our Phase 2 studies in the coming weeks. Aptumelant was designed to reduce or eliminate ACTH stimulation at the level of the adrenal, thereby lowering adrenal androgen output.

Speaker 3

Once adrenal hyperandrogenemia is controlled, patients who are taking excessive doses of glucocorticoid should be able to lower their dose and reduce or even avoid steroid therapy related adverse effects. Remember, the ACTH receptor in the adrenals is the only means by which ACTH drives the pathologic adrenal androgen output seen in CAH and the ACTH receptor is a single choke point at which this overdriven system might be turned off. Our ongoing Phase 2 open label sequential dose cohort study in CAH is evaluating safety and pharmacokinetics of aptumelint dosed for 3 months. In addition, we are evaluating pharmacodynamics and in CAH this is measured primarily using the androgenic biomarker androstenedione or A four as well as the cortisol precursor 17 hydroxyprogesterone. The goal of treatment is to reliably and reproducibly eliminate excess of exposure to adrenal steroids as reflected by these biomarkers.

Speaker 3

The patients in our study continued their pretrial glucocorticoids at unchanged doses, so we can observe the time course and durability of any response to aptumelnet itself. In future studies, we expect to evaluate glucocorticoid dose reduction once we know that the compound can reduce adrenal androgen output. As Scott mentioned, we will be presenting late breaking atumelint data at the upcoming Endocrine Society meeting in June. This will not include the full cohort of patients in the CAH study, but will comprise initial data from a subset of the first two dose cohorts. We expect these early results will give us directional information that will help guide developmental plans for etumelanin in CAH.

Speaker 3

Initial data from the Phase 2 single center trial in Cushing's disease will also be presented at the same meeting. With that, I will now hand it over to Mark to review the financials. Thank

Speaker 4

you, Alan. CorMedix continues to be in a strong financial position, having ended the Q1 with approximately $900,000,000 in cash and investments. This includes proceeds from the $350,000,000 private placement equity financing we completed in February. Our solid financial foundation is projected to fund our current operating plan into 2028. And this includes plans to commercialize paltucitine for acromegaly, the initiation of multiple later stage clinical trials in additional indications with paltuzutine and atumelanab, as well as continued investment in our pipeline.

Speaker 4

With respect to the financial results, research and development expenses were $53,300,000 for the quarter ended March 31, 2024 compared to $38,500,000 for the same period in 2023. The increase was primarily attributable to higher personnel costs and manufacturing and development activities, both of which were driven by the advancement of our clinical programs and the expansion of our preclinical portfolio. For the quarter ended March 31, 2024, general and administrative expenses were $20,800,000 compared to $12,200,000 for the same period in 2023. These increases were primarily attributable to higher personnel costs to support the growth of the organization. Net loss for the quarter ended March 31, 2024 was $66,900,000 compared to a net loss of $46,000,000 for the same period in 2023.

Speaker 4

Revenues were $600,000 for the quarter ended March 31, 2024 compared to $2,700,000 for the same period in 2023. Revenues during the current year's quarter were primarily derived from our paltucitine licensing arrangement with our Japanese partner SKK. And revenues for the prior year were associated with licensing arrangements for paltuzutine and CRM-nineteen forty one, another somatostatin targeted development candidate. Net cash used for operating activities for the quarter ended March 31, 2024 was 52,900,000 dollars We continue to expect our cash burn to be approximately $50,000,000 to $60,000,000 per quarter for the remainder of 2024. I will now hand it back to Scott for closing remarks before we begin Q and A.

Speaker 2

Thank you, Mark. We will continue to build on the strong progress this quarter throughout the rest of the year and beyond. We look forward to sharing that Tumelnet data in the coming weeks as well as providing continued updates as we progress paltucitin to regulatory submissions and as we make continued advancements in the exciting new programs beginning to emerge from our discovery efforts. Thank you all for your attention. Operator, we are ready to take questions.

Operator

Thank you. Ladies and gentlemen, we will now begin the question and answer session. Your first question comes from Yasmeen Rahimi of Piper Sandler. Your line is already open.

Speaker 5

Yes. Good afternoon, team and thank you for all your thoughts or remarks. Just I know we're going to quite a bit talk in the Q and A about CAH upcoming readout, but would love to actually dig into the Cushing's data set. I guess it's an interim look. It's been it's run by an NIH investigator that's going to share the data.

Speaker 5

I guess, I think we all understand cortisol reduction is key. Would love to get your thoughts on what we hope to learn from that study and what potential next steps be in development for Cushing's? And I'll jump back into the queue.

Speaker 2

Thank you, Yazz. Alan, can you take that question?

Speaker 3

Sure. Hi, Yaz. We are collaborating with a leading KOL at the NIH in our Cushing's disease study. This is a study in which the compound is dosed for 10 days while patients are in the clinical research center and there is frequent monitoring of many parameters, but especially pharmacodynamic speaking of most interest would be cortisol. These are patients with Cushing's disease who start with high levels of cortisol excretion.

Speaker 3

And of course, we'll be interested to see if cortisol is reduced during this 10 day dosing period. That is the information we would get from this study that I think will be of interest. We expect that the data we would present at the Endocrine Society meeting would give us directional kind of information to help guide our future development in Cushing's, Sort of like when we reported carcinoid syndrome data in December, it was directionally of interest. I would expect we would learn a great deal from what we've seen so far. Of course, it will be a subset of the patients as we discussed in our remarks.

Speaker 3

But still, again, I hope we'll have qualitative directional information.

Speaker 5

Thank you.

Operator

Your next question comes from Jessica Fye of JPMorgan. Your line is already open.

Speaker 6

Hey guys, good afternoon. Thanks for taking my question. What elements of etmelman's profile do you think will best differentiate it from CRF antagonist in CAH?

Speaker 2

Thank you, Jess. As we've said over the course of discovery and development in this program, that if you look at the mechanisms by which the adrenals controlled, they all converge on ACTH acting at its receptor on the adrenal, which is formed by the MC2 protein, But we'll just call it the ACTH receptor. It's the only way ACTH can act, and it's the only thing that the ACTH receptor does. And so by blocking that, we're blocking the single choke point of action of the whole hypothalamic pituitary adrenal axis on the adrenal. And we've always said we expect to achieve good blockade of adrenal activity, whether it's measured by adrenal androgens in CAH or by glucocorticoids in Cushing's patients.

Speaker 5

Thank you.

Operator

Your next question comes from Cory Ubonville of LifeSci Capital. Your line is already open.

Speaker 7

Thanks for taking our questions and love the new name for 4,89 4 atumelnet. I'm very intrigued by your endo abstract title in regard to CAH data. The title is atumelnet induces rapid and profound reductions of A40017 OHP in participants with CAH. The keyword for me there being profound. To the extent you can, can you help us frame expectations on data that we'll see at ENDO?

Speaker 7

And I guess, if you can't go into granular detail, at a high level, how satisfied are you with the pharmacodynamics you're seeing with atumelnet in comparison to the CRF1 antagonist? And we've also seen some mixed results lately across competitor CAH readouts. Can you help us better understand the types of patients that you've been enrolling in this Phase 2 study? Thank you.

Speaker 2

Yes. Sorry, Corey. I think you'll have to wait until Monday, June 3 at 12 pm Eastern Time when the embargo lifts before we can really get too deep into this. But we look forward to seeing you at our poster presentations and welcome everyone to our Investor Relations event, which is at the Omni Hotel on the third, the same day at 6 p. M.

Speaker 2

In terms of phrasing, sorry, can you repeat the second half of your question

Speaker 3

if you're still on the line?

Speaker 7

Yes, I guess at a high level, how satisfied are you with the pharmacodynamics you're seeing in comparison to some of the CRF 1 antagonist and we've also seen mixed results in competitor CAH readouts. And can you help us understand the types of patients that you've been enrolling into this Phase 2 study in terms of whether it be compliance or whether it be severity of disease or degree of control?

Speaker 2

Yes. I realize there's been a lot of people wanting to set the bar and I've always encouraged people to think about treating the whole disease, not defining a bar of 1 compound or another. In terms of how satisfied we are, again, you'll need to see the data at ENDO. And generally, maybe I'll just leave it at that. I'll just leave it at come and see us.

Speaker 2

We look forward to presenting it and talking to everybody about it.

Speaker 3

Maybe Scott, I could address the question on what sort of patients are enrolled in this study, if that would be helpful. Yes, please. Thanks, Adam. Okay. So these are patients these are adult patients with classic CAH, which means they have the most severe form of enzyme deficiency.

Speaker 3

So they're born with this condition and generally throughout life need to take glucocorticoid replacement. So these are all now adults with this condition who are all on glucocorticoid therapy. In general, they will start the study with elevated adrenal androgen levels. There will be a variety of disease severity that we look at. We're trying to be as inclusive as possible in this study.

Speaker 3

And it's a 3 month dosing period. During the 3 months, we administer a fixed dose of etumelant. The background pretrial glucocorticoid therapy has not changed during this study. As I mentioned during my remarks, our first goal is to assess how well 4,894 reduces adrenal androgen output in and of itself without the additional variable of adjusting glucocorticoid doses ultimately in future studies assuming 4,894 is successful at controlling adrenal hyperandrogenemia. Subsequent studies we would look at glucocorticoid dose reduction as well because a lot of these patients are on supraphysiologic doses of glucocorticoid and they would benefit from being brought down to the floor replacement dose levels.

Operator

Your next question comes from Joseph Schwartz of Leerink Partners. Your line is already open.

Speaker 8

Thank you. Congrats on the progress. Given the Phase II CAH altumelnet study continues to enroll patients, I was wondering if you can talk about what more you hope to learn or demonstrate beyond the interim data, which you'll be reporting at ENDO? Are there additional questions you need to answer before you can advance to Phase 3? And when will the next look at the CH trial be?

Speaker 8

Thank you.

Speaker 2

Thanks, Joe. Alan, why don't you take that question?

Speaker 3

Yes. So, we will be presenting a subset of the study. The goal of a Phase 2 study is to fully evaluate the relationship between the dose of an experimental agent and the safety of course, but also pharmacodynamic response at various doses. So this will be a subset. I think we will get good directional information from the doses tested.

Speaker 3

But we do want to complete the study to make sure we have that complete range of dose response evaluated to help us best design subsequent development for the compound.

Operator

Your next question comes from John Woleben of Citizens JMP. Your line is already open.

Speaker 9

Thanks for taking the questions. One more for me on 894 and then Carcinoid syndrome. When we're thinking about the data at ENDO, how do you balance the relative importance of a percent reduction in AAV4 versus achieving normalization as far as clinical development and then also management of patients in the real world? And then, wondering if you could give us some high level thoughts on the Phase 3 preliminary design in carcinoid syndrome?

Speaker 2

I will let 2 questions slip by on that one. But I'll take the first part and Alan maybe you take carcinoid syndrome. But generally percent is always just a shorthand and it depends on where you start for the magnitude of the effect that you might see expressed as a percentage. So I do think the goal of therapy is to get people as low as you can on their androgens so that you can adjust or get rid of the androgen effects and adjust the glucocorticoids to a physiologic level. So percent is a good shorthand and perhaps an easy way to make some comparisons, but in the end it's patients that is the focus.

Speaker 2

And by the way, it's not just biomarkers, it's the effect of those changes in hormones that may have on the symptoms and expression of the disease in these patients. And Alan, you want to comment on carcinoid syndrome?

Speaker 3

Sure. Yes. As we've reported Phase 2 data, we are actively designing the Phase 3 program for carcinoid syndrome. The plan of course is to review with the FDA the full data set from the Phase 2 study as well as our proposals for Phase 3 and to align with them on the design of Phase III. I can give you some sort of high level thoughts about Phase III.

Speaker 3

Again, we have to remember that we haven't had those regulatory discussions yet, so it's not set in stone. But in general, based on regulatory history in this disease state, I would anticipate we're looking at a placebo controlled trial. The most recent approval carcinoid syndrome involved a 3 month placebo controlled trial and I think that's kind of what we're anticipating here too. Of course, the key endpoints would have to do with the cardinal symptoms of carcinoid syndrome, diarrhea and flushing. And as we already reported in Phase 2, we see reductions in both the frequency of these episodes, but also the severity of diarrhea and flushing too with paltucitin therapy.

Speaker 3

And I think we will very likely very carefully measure those things in Phase 3 as well. And in terms of sample size, historically carcinoid syndrome pivotal trials, first of all, they're generally single pivotal trials for carcinoid syndrome. And the sample sizes in the past have ranged between roughly 80 150 patients. And based on our power calculations to date, I think that's right about the range I would expect for our Phase III trial as well. Hope that's helpful.

Speaker 9

Thanks for letting me sneak in too. Very helpful.

Operator

Your next question comes from Leland Kershull of Oppenheimer. Your line is already open.

Speaker 10

Hey, good afternoon. Congratulations on the progress and thanks for taking my questions. Also a couple for me on carcinoid, maybe for Alan. With the benefit now of a few months since the reveal from the Phase 2, want to hear of any feedback you've received from physicians with respect to their interest in using paltucitin in patients who are untreated on SRLs given the large population segment who is not currently on therapy? And I have a follow-up.

Speaker 2

Go ahead, Al.

Speaker 3

Thanks for the question. We, of course, work closely with a number of specialist physicians, oftentimes oncologists, who specialize in neuroendocrine to consumer patient care and also themselves usually treat those patients with carcinoid syndrome. A lot of them are our investigators and then our study steering committee and the feedback has been generally very positive from them. They're very excited about the data we have. And I would say pleased to be helping us think about what's coming up in Phase 3 and probably many of them would participate in Phase 3 as well.

Speaker 3

I think it's recognized by many of the physicians who treat this that there are some shortcomings with these injections that are the standard of care for the control of carcinoid syndrome. And we went through many of those limitations in my prepared remarks, but these are just very burdensome from patients in many ways. They're also technically difficult to deliver in a reproducible way and this has actually been shown in the literature in this patient population in particular. So, I think both the patients and the physicians have expressed to me at least positive thoughts that this would be a real contribution to the field.

Speaker 10

Thanks. And then further to the point of the data you've shown, so the 5 HIAA levels and serotonin were pretty well reduced by palticicine. It seems like that was much better than we've seen with the SRLs. Wondering, if that particular finding has resonated with respect to maybe longer term efficacy beyond, I think, the 8 weeks that you'd shown with the Phase 2 for longer term control of the cardinal symptoms? Thank you.

Speaker 3

Yes, it's an interesting question. I'm afraid I don't know the answer. I'm not sure the answer is even in the literature. The ability of the biomarker responses to predict longer term responses with respect to these tumors or the symptoms, not really established. These biomarkers are generally used in clinic primarily to diagnose carcinoid syndrome, But their ability to monitor therapy is not well established.

Speaker 3

But I would thank you for pointing out that we did see some actually pretty nice responses and it is hard to find those in the older literature and I suspect that might in part have to do with improvements in the methodology for measuring these things. We're using the latest assays for these biomarkers and I have a feeling that that may have contributed to our pretty clear symptom and biomarker responses that we saw. And we, of course want to leverage this for our Phase 3 program as well.

Speaker 2

And just

Speaker 9

to follow-up a little

Speaker 2

sorry, this is Scott. Just to follow-up a little bit, I did want to note your comment about potentially getting to those patients who currently aren't treated. And I think that is a unique opportunity. It's very surprising to me that there is a significant population of patients with carcinoid syndrome that are not being treated at this point, when they clearly should be. And I can only explain it by, somebody they must be making some judgment on the burden of treatment versus the burden of disease and or access to medicines.

Speaker 2

And it's causing far too many to not have access to medicines that would help them. So we look forward to try and find ways to bring this to more patients than are currently on the injectable depot therapies.

Speaker 10

Thanks so much for the color. Looking forward to hearing more, Endo.

Operator

Your next question comes from Douglas Tsao of H. C. Wainwright. Your line is already open.

Speaker 11

Hi, thanks for good afternoon and thanks

Speaker 3

for taking the questions.

Speaker 11

I was just curious, maybe Scott, on the earlier stage pipeline, you have a number of sort of therapeutic areas that you're targeting, many of which you're sort of talking about candidate selection for this year. I think you've talked about sort of diabetes and obesity for something for next year. I guess, what's the or is there any kind of prioritization within those? And how do you think about sort of the pace that those would go into the clinic and start to read out with you guys have a track record for doing sort of innovative early stage studies that give us pretty good PD data early on in development. And I'm just curious if that's how you anticipate seeing those for those candidates as well?

Speaker 11

Thank you.

Speaker 2

Yes, the emerging pipeline is really super exciting and we are really committed to what I call the craft of drug discovery. So we want to make sure that these are really the best possible molecules we can make before we invest in development. And so those programs are now really starting to get close to molecules that might be good enough. PTH is probably first. We've been doing some non GLP tox studies on multiple candidates and it looks like the team is getting close to selecting the best one out of several good ones.

Speaker 2

And then the other programs are successively behind that. Fortunately, we've been in a financial position where we don't need to make difficult prioritization And I And I do think there's a little bit of just internal prioritization we have to do as we balance workloads between some of the different projects. But largely all projects are moving forward as fast as we can And I'm optimistic that that's going to leave a whole sequence of upcoming clinical information on these programs over the next 12, 18, 24 months.

Speaker 11

Okay, great. That's really helpful and congrats on the progress.

Speaker 2

Thanks.

Operator

Your next question comes from Catherine Novak of Jones Research. Your line is already open.

Speaker 12

Hi. Thanks for taking my questions. I'm just wondering, when it comes to commercialization, what's the overlap in terms of treatment centers and prescriber base for CAH and acromegaly? And then would there any overlap extended carcinoid syndrome? Is that a completely different

Speaker 5

institutions that you're looking at?

Speaker 2

Thanks, Catherine. It's a high degree of overlap and maybe Jim you could get into some more detail there.

Speaker 13

Yes. Thanks, Katherine. In terms of acromegaly and especially carcinoid syndrome, when we look at the 35 to 40 pituitary treatment centers, typically they are academic centers that also overlap with the National Comprehensive Cancer Center Network. So when we're doing some sales force sizing, we see a lot of overlap between acromegaly and carcinoid syndrome. Even in terms of endocrinologists, there's a high degree of overlap with acromegaly and Cushing's disease, of course, because it's pituitary, but we're also seeing the same for congenital adrenal hyperplasia.

Speaker 13

So a lot of the specialist endocrinologists are seeing all 3 pituitary or adrenal diseases.

Speaker 2

And I'll just add that that was really part of our long term strategy when we started getting into these indications. So that not only from a commercial point of view do we start building into the same centers and same prescribers, but also from a development point of view, so that we start using the same investigators and centers again and again and again and trying to find synergies and ways of working well together as those relationships go for the long term.

Operator

Your next question comes from Jeffrey Huang of Morgan Stanley. Your line is already open.

Speaker 4

Hi, this is Michael Riad on for Jeff Hung. Thank you for taking our question. Circling back to the Phase 3 designs for carcinoid syndrome, is there any ability for the study design to accommodate or potentially show the ability to prevent like breakthrough symptoms and the typical waxing and waning versus SRLs, maybe during the initial screen or washout. Just wondering if there's any potential for that analysis? Thanks so much.

Speaker 2

Thanks. I think that's an important question and we are asking ourselves that. Alan, you might want to comment a bit on it.

Speaker 3

Yes, it's a very important concept because that's as I was talking earlier about the limitations of the current injection therapy for carcinoid syndrome. That is a major issue is you take these long acting injections sometimes more frequently than once a month and yet you still have these days where you have active breakthrough of either diarrhea or flushing or both, sometimes more than just a day. And these patients often end up having to take additional medication, sometimes anti diuretals or sometimes even short acting sub q boluses of octreotide itself on top of the long acting octreotide they're already taking. Why that kind of breakthrough occurs is not fully understood, but I suspect that it might be related to some variability in exposure to the drug from month to month. We do know that there is variability in technique of actually accurately delivering, for example, octreotide to the intramuscular space.

Speaker 3

So I suspect that contributes to this breakthrough phenomenon. And yes, in our trials, we will be very interested in asking patients every day how they're feeling using an electronic diary as we did in Phase II and as we did in Phase III for acromegaly. And I am hoping we will learn interesting things about whether that problem we see with these long acting injections could potentially be solved with a daily oral dose of a simple oral agent.

Speaker 4

Thank you so much. That's very helpful. I appreciate it.

Operator

Your next question comes from Brian Skorney of Baird. Your line is already open.

Speaker 14

Hey guys, this is Charlie on for Brian. Thanks for taking our question. So just want to switch gears a little bit towards the PTH asset or assets. Just kind of wanted to ask what from the presentation earlier this year at the Bone and T SCOREN Research Conference really gave you confidence in the profile of the molecules you're developing. And if, maybe you could kind of walk us through what excites you about it as well as if this is kind of the profile that you're looking for from the other assets that you're selecting from?

Speaker 14

Thank you.

Speaker 2

Got it. How about, Alan, I'll talk about the preclinical and you can talk about why we're excited about it clinically. But very much this is like many of our programs where the endocrinology in animal model species is almost identical to the endocrinology in humans. And we know that it's very robust way in rats, for example, to induce hyperparathyroidism by infusing excess of parathyroid hormone and we can watch calcium go up. And then we can introduce 1 of our antagonists and watch calcium normalize.

Speaker 2

We can also take normal rats and give them PTH antagonists and see their PTH levels rise. So this type of pharmacodynamic response in a model system is very much the same type of thing we would do in a healthy volunteer. And it goes up and down our pipeline. And it's a reason why from a business perspective, endocrinology is just such a great field because you do so much derisking so early on, whether it's in animal models, which closely mimic humans or it's early healthy volunteers or early patient studies where you're measuring biomarkers that are completely objective and well defined. But maybe Alan, you can comment on the clinical need and why we're excited about PTH antagonist for these different patient populations.

Speaker 3

Yes, sure. This is a novel mechanism of action for that could potentially help a great number of patients who have parathyroid hormone excess for any number of reasons. And by the way, also parathyroid hormone related protein excess. So beginning with hyperparathyroidism, this is a fairly common endocrine disease, primary hyperparathyroidism in which the one of the parathyroid glands in the neck typically overgrows and causes unregulated excess secretion of parathyroid hormone. That results, as Scott mentioned, in hypercalcemia, high calcium levels in the blood, but it's really a multi organ systemic disease that also damages the bone and the kidneys in particular.

Speaker 3

And the hypercalcemia itself can cause sometimes very serious symptoms. Now fortunately for patients with primary hyperparathyroidism, there are very, very effective surgical options available and many of these patients are cured surgically. However, there is a very important subset of patients who don't get cured by surgery, sometimes because more than one gland actually enlarges in some patients. And there is really a great number of patients who could benefit from having a medical option to control hyperparathyroidism when surgery has not worked. And the other thing I would point out is even with patients who potentially could have surgery, it turns out a lot of them don't have surgery for any number of reasons, including the fact that they may not be surgical candidates.

Speaker 3

And so therefore, I see a lot of potential for a medical option in this area. That's just one potential that's probably the most straightforward indication, but there's also something called hypercalcemia malignancy, which is caused by a parathyroid hormone related protein, which also binds to the PTH receptor. Those patients could also use a new option. There are treatments available, but they all have limitations and these patients can be quite ill. And I think it's an exciting prospect also potentially for the future for a PTH antagonist.

Speaker 3

And then there's more, but we don't have time to talk about more.

Speaker 14

Great. Thank you very much.

Operator

Your next question comes from David Lebowitz from Citi. Your line is already open.

Speaker 3

Thank you for taking my question. With respect to the data being presented for CAH, how should we benchmark it versus what we've seen from other therapies? And what should we expect? And conversely what should we not expect?

Speaker 2

Alan, maybe you want to reiterate that.

Speaker 3

Yes. I mean, I think, again, we're expecting directional information in the biomarker responses. Again, as we discussed, it's more than just what's the percentage reduction in the biomarkers. It's also about how many patients actually get into get normal levels of biomarkers. And then there's all the clinical features of the disease we want to carefully assess when we look at our data.

Speaker 3

So again, it's this our Phase 2 interim data will not be a statistical exercise, but I'm hoping we'll get good directional guidance in terms of what doses may or may not be effective and what doses and designs we may want to contemplate for future development beyond Phase 2? Thanks for taking my question.

Operator

Your next question comes from Dennis Ding of Jefferies. Your line is already open.

Speaker 15

Hi, thanks for taking our questions and congratulations on all the progress. If I can ask on CAH, maybe just talk about how you're thinking about having to go to the high 160 milligram dose as it was an optional cohort. And just wondering if that cohort has started enrolling or not or do you even plan to? Thank you very much.

Speaker 2

Alan, do you want to talk about how we think about cohorts and dose selection?

Speaker 3

Yes. So, this is a sequential dose cohort study. And in the 1st cohort of patients with CAH receive an 80 milligram once per day dose of eptumelimin. This is based on the Phase 1 healthy volunteer data showing that that dose looked like it should be effective. After we complete the 1st cohort of dosing, all the data from that cohort is reviewed by a safety review committee and that committee then recommends the dose for the next cohort.

Speaker 3

That dose that next cohort could be higher or a lower dose. We'll certainly share that information at the Endocrine Society meeting as part of the scientific presentation. And I think it's fair to assume we'd have patients from the 1st cohort as well as some of the 2nd cohort as well.

Operator

There are no further questions at this time. I would hand over the call to Doctor. Scott Struthers, Founder and Chief Executive Officer for closing comments. Please go ahead.

Speaker 2

Thank you everybody for being with us today and we look forward to seeing many of you in Boston in the beginning of June and throughout the year as more and more interesting things start coming out from the pipeline. Thanks again for your time. Good night.

Operator

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation and you may now disconnect.

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Earnings Conference Call
Williams Companies Q1 2024
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