Spruce Biosciences Q4 2023 Earnings Call Transcript

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March 13, 2024

There are 11 speakers on the call.

Operator

Greetings. Welcome to the Spruce Biosciences Conference Call. All participants will be in listen only mode. After today's presentation, there will be an opportunity to ask questions. Please note, this conference is being recorded.

Operator

At this time, I'll now turn the floor over to Sameer Garib, President and CFO of Spruce Biosciences. Sameer, you may begin now.

Speaker 1

Thank you, operator, and thank you all for

Speaker 2

joining us this afternoon.

Speaker 1

With me on today's call are Doctor. Javier Schwarcberg, SPRUCE's Chief Executive Officer Doctor. Will Charlton, SPRUCE's Chief Medical Officer Doctor. Irina Bankos, Principal Investigator in the CAMELIA-two zero three study and Associate Professor of Medicine and Endocrinologist at the Mayo Clinic and Doctor. Paul Thornton, Principal Investigator in the CAPTAIN-two zero five study and Medical Director of the Endocrine and Diabetes Program at ACH Center of Excellence.

Speaker 1

This afternoon, SPRUCE issued a news release announcing top line results from a Phase 2b CAMELIA-two zero three clinical trial, of tildesrefonds in adult classic congenital adrenal hyperplasia also known as CAH and its Phase 2 CAPTAIN 205 clinical trial of tildesrefonds in pediatric classic CAH. SPRUZ also announced its financial results for the year ended December 31, 2023. Please note that certain information discussed on the call today is covered under the Safe Harbor provisions of the Private Securities Litigation Reform Act. We caution listeners that during this call, Spruce Management will be making forward looking statements. Actual results could differ materially from those stated or implied by these forward looking statements due to the risks and uncertainties associated with the company's business.

Speaker 1

These forward looking statements are qualified by the cautionary statements contained in First's press release as issued today and the company's SEC filings, including its most recent Annual Report on Form 10 ks and subsequent SEC filings that it has made. This conference call also contains time sensitive information that is accurate only as of the date of this live broadcast, March 13, 2024. Sprouts undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances after the date of this conference call. Now finally, during today's Q and A session, we ask that you please direct all questions to Javier and he will request that either Spruce Management and Doctors Banco and Thornton elaborate as appropriate. Now, I'd like to turn the call over to Javier.

Speaker 1

Please go ahead, Javier.

Speaker 3

Thank you, Sameer, and thank you, and good afternoon to you all. As a physician and drug developer, I have dedicated my career to advancing new and innovative solutions for underserved patients, families and communities suffering from rare orphan diseases. At Struz, we focus on transforming the care of patients with rare endocrine disorders, including CH. For nearly a decade, our team of innovators and drug developers has sought to advance new therapeutic options. Today, our focus is on tildazifone, a once daily tablet in development that we believe has the potential to transform the treatment paradigm in CAH and positively impact the lives of patients and their families.

Speaker 3

CH is a rare genetic disorder that impacts patients throughout their entire lives from birth. It's estimated that the total classic CH population is approximately 20000 to 30000 people in the U. S. And 50,000 in the EU. CAH affects the adrenal glands and due to an enzymatic deficiency leads to an inability to make cortisol and an overproduction of adrenal androgens.

Speaker 3

Due to the severity of the disease, every state across the U. S. In most developed nations have established newborn diagnosis screening programs. From birth, newborns are placed on glucocorticoid replacement therapy, also known as steroids or GCs to correct for the missing cortisol. If left untreated, patients become susceptible to adrenal crisis, which can be life threatening.

Speaker 3

This risk continues over the person's lifetime and never goes away. The overproduction of adrenal androgens is also an important issue as it can lead to life compromising effects such as early puberty, obesity, short stature, acne, facial hair in females, psychiatric problems and impaired fertility in both sexes. Elevated adrenal androgens levels are generally managed with above physiologic doses of GCs, which over a lifetime carries several well known debilitating effects, including obesity, cardiac problems, hypertension, insulin resistance, high lipids, cushion going appearance, bone loss which may result in excess bone fractures, sleep issues and anxiety. Unfortunately for patients, there has not been a steroid sparing treatment option and frankly minimal innovation since GCs became available in the 1950s. So why for the past 70 years has science been unable to make meaningful advances in the CH therapeutic landscape?

Speaker 3

Well, key to the problem is the perception that chronic GCs on a biophysiologic doses along with chronically elevated and renal hormones will not result in significant chronic consequences to one's life. That's simply untrue. And this perception must change. It is a cumulative lifetime over treatment that creates problems and matters. Better options are desperately needed that allow for physiologic, meaning more balance to reduce while controlling the elevated androgens.

Speaker 3

At SPRUCE, we are focused on changing the treatment paradigm by developing tildasafone as an oral once daily non steroidal treatment option. It is a corticotropin releasing Factor Type 1 or CRF1 receptor antagonist designed for androgenic control while on physiologic doses of GCs, which was not possible until now with the current steroid therapies. We are committed to unlocking the full therapeutic potential of tlodasalone and developing a quantifiable and meaningful improvement over today's standard of care in CAH, which is why we were disappointed by the results from the CAMELIA-two zero 3 program in adult CAH patients with severe hyperandrogenemia. Though this study did not achieve the primary endpoint, we garnered important data about the challenges of treating severe hyperandrogenemia within this patient population. CAMELIA-two zero three is the 1st study of its kind to focus on a very difficult to treat patient population with poorly controlled disease, as evidenced by the mean understeinedione or A four levels of patients who enrolled in this study, which was over 5 times above the upper limit of normal.

Speaker 3

This was an important study to learn how best to address this refractory and difficult to treat group of CH patients with severe chronic hyperangiabenia, often attributed to challenging realized compliance with daily glucocorticoids. Despite our efforts and strong study conduct standards, overall compliance with study medication and GCs was low in CAMELIA-two zero three resulting in lower than expected we remain confident in the therapeutic activity and potential of tildasifan. We will explain why today. We are hopeful and look forward to reviewing the results of CAMELIA-two zero four, which is expected to read out in the Q3 of 2024. The CAMELIA-two zero four study is focused on assessing GC reduction, a potentially registrational endpoint in a less severe patient population of adult CH patients with relatively controlled A four levels and historically better adherence to daily GC therapy, which gives us further confidence.

Speaker 3

A recent Phase 3 study investigating another CR1 receptor antagonist in a patient population similar to that of CAMELI-two zero four demonstrated statistically significant responses to treatment based on recently released data. Additionally, we are encouraged by the initial positive top line results from our CAPTAIN-two zero five study in children and adolescents. The therapeutic activity we observed in this study suggests that pildasafone even at lower doses may enable clinically meaningful reductions in A four and allow for GC reduction in children and adolescents at CAH. I will now turn the call over to Doctor. Will Charlton, our CMO, to review our top line study results.

Speaker 3

Will?

Speaker 4

Thank you, Javier, and good afternoon all. As a pediatric endocrinologist, I've cared for people living with CAH and have a very personal connection to this community. I've dedicated my career to making scientific progress and improving the lives of patients suffering from rare endocrine disorders. The global Camellia program in adult classic CAH is comprised of 2 Phase 2b studies designed to address the unmet medical needs of 2 subpopulations of adults. CAMELION-two zero three assesses A form reduction in adult CH patients with severe hyperandrogenemia, while CAMELIA-two zero four assesses GC reduction in adult CAH patients that are on super physiologic GC doses and have normal or near normal A four levels.

Speaker 4

Our program underscores our initial strategy to address the entirety of the adult classic CAH patient population by targeting 2 distinct groups with different challenges. Those with excessive adrenal androgen levels, the 203 study and those with excessive GC usage, the two zero four study. CAMELIA-two zero three enrolled 96 participants 0.84 level of 11 51 nanograms per deciliter, which is over 5 times the upper limit of normal. The study did not achieve the primary efficacy endpoint of assessment of dose response for the change in A-four from baseline to week 12. 200 milligram once daily of tildasifant demonstrated a placebo adjusted reduction from baseline in A four of minus 2.6 percent with a non significant P value at week 12.

Speaker 4

Seldazepamc was generally safe and well tolerated at all dose ranges with no treatment related serious adverse events. Most adverse events were reported as mild to moderate. The results from CAMELIA-two zero three highlight the challenges of treating severe hyperaneridinemia within this patient population, many of whom were ineligible for other CAH clinical trials and underscores a potentially different treatment paradigm that may be necessary to affect to effectively address the unmet need in these patients. In fact, the effective treatment of CAH in the context of severe hyperaneranginemia may be different from the approach needed to manage GCXS in patients with normal or near normal levels of androgens. The differences between these two patient populations are quite evident when you review the baseline characteristics for CAMELIA-two zero three and CAMELIA-two zero four.

Speaker 4

The mean adrenocorticotropic hormone or ACTH level was nearly 7 times the upper limit of normal, while the mean A four level within Camellia-two zero three was above 5 times the upper limit of normal. Compare that to the levels in CAMELITY-two zero four which were at or near the upper limit of normal. 17 hydroxyprogesterone or 17 OHP in cumulative 203 was more than 80 times the upper limit of normal compared to the level in 204 which was approximately 28 times the upper limit of normal. Further, patients enrolled in CAMELI-two zero three have severe and refractory disease as a result of patient specific physiology such as degree of 21 hydroxylase deficiency or inability or unwillingness to tolerate high doses of steroids, which makes them more susceptible to being in a hyperandrogenic state in the first place. We know from clinical practice that patients with hyperanergenemia generally require increases in their background steroid therapy and in some cases changing changes to their dosing schedule or their type of GC to reduce adrenal androgens.

Speaker 4

When adrenal glands are highly overstimulated, especially for a long time, they become increasingly hyperplastic and more difficult to control. In these cases, short term treatment with higher steroid doses is sometimes required to involute adrenal tissue and to reduce adrenal androgen production. This combined with results from our study offers us insights into a potentially different treatment paradigm needed for this population and considerations for optimizing the combination of tildesophant and steroid dosing to address the ACTH overdrive in CAH patients suffering from severe hyperanerginemia. Now this is in very stark comparison to patients in our CAMELIO-two zero four study, who are more controlled by virtue of their higher GC doses and likely suffer from less hyperplasia of the adrenal glands. Patients with higher GC doses and normal or near normal androgen levels are also generally more consistent with GC therapy and easier to manage, but they carry a higher risk of steroid associated comorbidities.

Speaker 4

We believe that for this group of relatively well controlled patients in CAMELI-two zero four, the goal should be to sustain ACTH suppression, which would allow for a gradual decrease in steroid dosage, ideally to physiologic replacement levels. For this reason, we do not believe that results from CAMELIA-two zero three are necessarily suggestive of potential results from CAMELIA-two zero four. This along with feedback from many experts as well as our internal analysis reinforces our confidence in the therapeutic potential and activity of tildesrefonds And we look forward to the 204 results in the Q3 of 2024, which will provide a critically important and more complete picture of its efficacy. Moving forward, we plan to continue our analysis of CAMELIA-two zero three and plan to use our study learnings to potentially inform a future Phase 3 program. Now let's discuss the positive initial top line results from our pediatric CAH program.

Speaker 4

The Phase 2 CAPTAIN-two zero five study is focused on addressing the unmet medical need in pediatric classic CAH patients, which represents approximately 25% of the total patient population. CAPTAIN-two zero five enrolled 30 children between 217 years of age. They had a mean baseline GC dose of 14 milligrams per meter squared per day and a mean baseline A four level of 372 nanograms per deciliter. The study characterized both the safety and pharmacokinetic profiles of tildesafone in children as well as changes in androgen levels over 12 weeks of treatment and the ability to reduce daily GC doses in patients achieving normal

Speaker 5

A four levels.

Speaker 4

During the initial 4 weeks of the trial glucocorticoid treatment was not modified. 73% of all patients or 22 of 30 met the efficacy endpoint of A four or GC reduction at baseline or rather from baseline at 12 weeks of treatment with tilvastropod. 70% of patients with elevated baseline A four values or 16 of 23 demonstrated an A four reduction at week 4. Chlazantinibol was generally safe and well tolerated at all dose ranges and no treatment related serious adverse events were reported. Although the CAPTAIN study met the efficacy endpoints, the results were less consistent than anticipated and without clear dose response.

Speaker 4

Pharmacokinetic results suggest that children clear chilgastrofant more rapidly than adults do, which is common with many drugs due to differences in drug metabolism across age and developmental stages. It is not uncommon for children to require relatively higher doses than adults in order to achieve optimal exposures of drugs. So we are encouraged by the activity observed thus far at suboptimal doses in this Phase 2 dose ranging study. And we plan to continue to evaluate the optimal dose with top line results anticipated in the Q4 of 2024. Overall, as a pediatric endocrinologist, I witnessed firsthand the unmet medical needs and challenges of people with CAH who lack steroids bearing treatment options.

Speaker 4

I remain encouraged by our results today and the potential of Tildasirfant to deliver transformative care for patients and families living with CAH.

Speaker 3

Thank you, Will. I will now ask Sameer Gharib, our President and CFO to briefly review our 2023 financial results. Sameer?

Speaker 1

Thank you, Javier. Our cash and cash equivalents as of December 31, 2023 were 96,300,000 dollars The company currently has over $81,000,000 in cash and cash equivalents. We have made the difficult but necessary decision to streamline our operations and have implemented cost reduction measures including termination of the CAMMILLA-two zero three study and a reduction in force of approximately 21%, which has extended our cash runway through the end of 2025 beyond top line data readouts for CAMELIA-two zero four and additional dose ranging data from CAPTAIN-two zero five. Collaboration revenue for the year ended December 31, 2023 was $10,100,000 compared to nothing in 2022, reflecting the partial recognition of the $15,000,000 upfront payment received from cauchten Pharmaceutical in connection with the company's strategic collaboration with Kaken to develop and commercialize tildasirfant for the treatment of CAH in Japan. R and D expenses for the year ended December 31, 2023 were 49 point $4,000,000 compared to $35,200,000 in 2022.

Speaker 1

The overall increase in R and D expenses was primarily related

Speaker 4

to the advancement of our CAMELIA and CAPTAIN studies. G and A

Speaker 1

expenses for the year ended December 31, 2023 were $12,700,000 compared to $12,100,000 in 2022. Total operating expenses for the year ended December 31, 2023 were $62,100,000 compared to $47,300,000 in 2022. These include non cash stock based compensation expense for the year ended December 31, 2023 of $4,600,000 which compared to 3,600,000 dollars in 2022. Net loss for the year ended December 31, 2023 was $47,900,000 compared to $46,200,000 in 2022. Now finally, common shares outstanding as of December 31, 2023 were 41,000,000 shares and 61,300,000 common shares on a fully diluted basis.

Speaker 3

Thank you, Sameer. We consider it an honor of being able to partner with the CH community and through innovation open a new chapter in the management of CH with a possible life changing medicine. I recognize the potential transformative impact of trovacipan and we have a strong sense of urgency to deliver on our commitment to the CH community. Across the landscape, this is an incredibly important and exciting time for CH patients and families and making progress in a therapeutic area that is underserved requires doing things differently and in partnership with them. We at Cruise have a clear purpose and that is to improve the standard of care for the communities we serve.

Speaker 3

That is our true north. Looking ahead to the Q3, we're eager to report top line results from Camellia-two zero four, which is focused on assessing GC reduction in potentially registrational endpoint in adult CH patients with relatively control A four levels and better GSE compliance. Assuming positive results from the CAMELIA-two zero four and CAPTAIN-two zero five, we plan to meet with the U. S. FDA and comparable foreign regulatory authorities to outline the design of a registrational clinical program in adult and pediatric classic CH.

Speaker 3

In conclusion, I would like to extend our deep appreciation to all the patients, families, study team and investigators who participated in the CAMELI-two zero three and CAPTAIN-two zero five clinical trials. Your support advances our understanding of the disease and our mission to deliver a meaningful improvement over today's standard of care in CAH. I also want to express my gratitude to all of our employees, including those departing Spruce for their contributions and tireless dedication to advancing our mission and bringing forward new and innovative therapies for CH and other rare endocrine disorders. Operator, we may now open the line for questions.

Operator

We will now begin the question and answer Our first question today is from Joseph Schwartz with Leerink Partners. Please go ahead.

Speaker 6

Hi, my condolences on these results. I was wondering, it sounds like you're not just attributing the miss to poor compliance, but also the patient population which was enrolled in 203 with their severe and refractory disease. So I was wondering how much did pildasirfon reduce A-four in patients who were compliant to the regimen and or who had less extreme A four levels in Study 2 zero three. Have you done any analyses looking into the data to see such things in order to explore whether there's any data supporting your hypotheses to explain the miss in Study 203? And then I have a follow-up.

Speaker 3

Hi, Joe. This is Javier. Yes, we're in the process, Joe, of really understanding the relationship between exposure and response in the trial. Clearly, we see that upon increased levels of different doses of TILDA in the 203 study of 50, 100, 200, we see increased levels of exposure. But overall, the overall exposures were multiple folds below the exposures that we had seen in the 202 study, which was a proof of concept trial that informed the design for the 203 program.

Speaker 3

And it is because of that that we attribute the kind of you can actually assess the sequence, right, lesser compliance, less exposure, lesser overall benefit. I would like to pass on some of this response to Doctor. Vankos. Irina, perhaps it would be great if you can provide your point of view on the type of patients that we treated in the 2 or 3 study and how that translates into your clinical practice?

Speaker 7

Yes. Thank you for this question. So clearly patients enrolled in 203 were not quite representative of majority of patients with CH at least seen in adrenal centers. And what I mean by that, these are the patients who were less likely to be controlled as you have shown based on the endocrine dying levels. So it's a bit difficult to apply the results of the study to the whole population of WTH, but to bring that these are very unique patients on low glucocorticoids and with more uncontrolled olebastinib.

Speaker 6

Okay. And why do you think you're seeing an inverse baseline effect when Neurocrine saw strong positive baseline effect in Catalyst where patients with higher A four baseline benefited more with a larger reduction in A four on a related molecule?

Speaker 3

Well, I wouldn't say that thanks, Joe, for the question. I wouldn't say that the baselines between the Neurocrine program and the 203 study are similar rather consider them quite different. The baseline A four value was 620. Our baseline A four value is 11 51 nanograms per deciliter and overall GCUs in the 2 or 3 study was 27 milligrams relative to 232 in the Neurocrine program. I think that the explanation that we have given or at least the current hypothesis is that it's related to the overall compliance and the overall exposure of drugs.

Speaker 3

So we didn't really achieve the exposures in the 202 study that we were hoping to achieve and enhance the lesser overall impact on the biomarkers that we have tested. I think that part of the reason why we didn't achieve the exposures is because of the compliance rates, which were remarkably low. And I think that reflect frankly what typically happens in practice, right? And you just heard what Doctor. Banco said to say, the compliance rates in the 203 study were approximately 50% of patients were about 80% compliance and we know that 80% compliance isn't terrific.

Speaker 3

I mean, patients are missing 2 out of 10 doses and we know how sensitive it is for patients to how sensitive A four is in the context of missed doses. So yes.

Operator

Right. I guess

Speaker 6

assuming A four didn't change much in the placebo arm and knowing that around half of patients were generally compliant, this would still imply that a 4 only decreased by around 5% amongst compliant patients. So I'm just trying to understand, are you attributing the miss to both the poor compliance and just the drug not working in really high A four levels at baseline. And I'm just a little bit confused by that because catalyst, I thought showed us that cremessefant worked better in people with A 4 that was higher in baseline in that trial recognizing that the A 4s overall were lower in catalyst. So why would that relationship breakdown at a much higher A-four levels?

Speaker 3

The way we understand this, Joe, is that the exposures need to be adequate to control patients with CEH, right. And this patient population tends to be generally more difficult to control. The 2 or 3 patient population is more severe, is more advanced, tends to be more refractory to treatment, therefore requiring adequate levels of CR1 receptor antagonism to induce a response. I mean, the comment that we made earlier that patient maybe the patient population requires more intense management with corticosteroids to first control the disease and later to put the disease to be maintained and more on the CR-four and receptor antagonists alone may frankly hold true. It is definitely a fact that we did not achieve the exposures that were necessary to control this patient population in the 2 0 3 study.

Speaker 3

And it is also a fact that the exposure seen in the 2 0 3 study are folds lower than the exposures that we saw in 2 0 2 in the same population of elevated androgens and characterizes as poor control. Now the patient population in 204 is very different, right. These are this is a group that generally has adrenal that are more under control that have lesser extent of hyperandrogenemia, they tend to be more compliant with therapy and we have strong reasons to believe that the full study will the full study will behave differently.

Speaker 8

Okay. Good luck. Thanks for taking my questions.

Speaker 3

Thank you, John.

Operator

The next question is from Gregory Renza with RBC Capital. Please go ahead.

Speaker 5

Hey, good afternoon, Javier. Thanks for holding the call, taking the question. And also apologies on the sorry about the ultimate results here. Javier, just as you think about the design that you had for 203, certainly with respect to the screening and the run-in, I'm just curious if you could talk a little bit about how that's fair to your expectations? What could have been done to maybe mitigate for this or not as you think about the compliant or non compliant population?

Speaker 5

And maybe just as you talk about you and the docs talk about the 204, if you could just walk us through a little bit about the rationale about why the compliance expectation would be better? Certainly, you've touched on that, but just expand a little bit about anything quantitative that you see that gives you confidence in those areas. Thanks so much.

Speaker 3

Thank you for the question, Greg. So with relates to 203, frankly, we've designed, I think that's a very thoughtful study. The early part of the trial had a running on the front end of the trial, there was a running period of about 6 weeks. During those 6 weeks, we assessed compliance with study drug in compliance with corticosteroids and didn't allow patients in the trial that were less than 80% compliant. Frankly, that was done to ameliorate and reduce the possible placebo effect and with the hopes that we were going to dismiss from entry patients that weren't going to be compliant during the trial.

Speaker 3

Certainly, that wasn't enough. And we despite doing that, we were not able to attain the levels of compliance that we were hoping. The study was conducted to a high standard with quick robustness and very significant oversight with I mean, I'll let Will talk a little bit about the efforts that we put in place to ensure that people stay compliant during the course of a trial. Before I pass it on to actually Will, why don't you cover that and then we can address the question that Greg had on to offer? Sure.

Speaker 4

So it became evident early that we were people were having trouble understanding how to take tildesafone with food and the right time. So we launched some campaigns, some educational campaigns around how to take it correctly, how to take it with food. And also around compliance with steroids. In spite of those efforts, we do see a meaningfully lower compliance rate in this study than in other studies. And I think that's reflected in our exposure levels that we've seen.

Speaker 3

Yes. Thanks for that, Will. So let's talk about the 2 or 4 question that you had on compliance and why do we have confidence that things are going to be different for Q4. I'll ask Karina in a moment, Doctor. Vancos in a moment to comment on her experience in patients in her practice that are more similar to the 204 patient population.

Speaker 3

But we've looked at compliance in 204, Greg, and all along, compliance in the 204 study has been much, much better than the compliance that we've seen in 203. As of now, the ongoing compliance rate based on recent data appears to be north of 80%. And that frankly gives us reassurance that we'll achieve the total exposure that are required to demonstrate efficacy. And as I said before, I truly believe that the that probably what will be needed to control to maintain a patient in control in 2 0 4 is likely very different than the CRF exposure necessary to induce control in refractory 2 or 3 patient like. But I'd like to ask Doctor.

Speaker 3

Vankos about her point of view here and how this relates to her practice.

Speaker 7

So I guess in relation to 2 zero three population and high endocrine dying levels and compliance. So first, why would we see elevated androstenedione in CAH? It's really 1 or more than three things. Number 1, taking lower glucocorticoid dose than is needed. Number 2, being non compliant with your glucocorticoid dose.

Speaker 7

And number 3, severe CAH, meaning high glucocorticoid dose. So considering that the average dose of glucocorticoids in 203 study was not particularly low. Clearly, it's one of the 2, right? So it's either CVSAH or non compliance. Earlier when I said it's a bit of a sort of unique population of patients this age in one of the 3 categories.

Speaker 7

So I hope that answers your question.

Speaker 3

Thank you, Irina. Perhaps Irina, if you can comment on 2 or 4 patients, the type of 2 or 4 patients that you see in your practice and whether they tend to be different than the patients that we enrolled in 2 or 3 with a focus on compliance, but they tend to be more compliant with therapy?

Speaker 7

Yes. Well, so by describing the population that went into 203, we just can contrast the one that went into 204. Those were the people on slightly higher glucocorticoid dose, clearly more compliant with low understinibine levels reflecting the compliance. So you have sort of like a natural division here between 2 types of population. And definitely the 204 population is what probably is more representative of most patients followed by adrenal centers.

Speaker 3

Thank you, Doctor. Landers. Rick, I hope our response addresses your question. Perhaps we can pass it back to the operator to see if there are any more questions.

Operator

And the next question comes from John Wallabyun with JMP Securities. Please go ahead.

Speaker 2

Hey, thanks for taking the question. Couple on 205 and then one circle back to 204. Can you tell us what the actual A four and GC reductions were in 205?

Speaker 3

We'll be disclosing those results probably in upcoming meeting later in the year, Tom. Do you tell me what specifics?

Speaker 2

Yes. Yes. Okay. So we'll stay tuned there. And it sounds like you don't think that 204 is going to be sufficient to submit to regulatory authorities on its own.

Speaker 2

Is that correct?

Speaker 3

Well, it will depend on the strength of the evidence following 2 zero four, but I think it is quite likely that we will require will be required to conduct a confirmatory Phase 3 trial to support the results from Fluor.

Speaker 2

And last one for me. Can you talk a little bit about the titration regimen in 204? If patients are coming in near the upper limit of normal at baseline, will they be able to start titrating down their GC dose immediately? Can you just speak a little bit about that algorithm in Q4?

Speaker 3

Yes, they would. So patients that come in, so we titrate we have a titrating algorithm that's based on A four values. When the A four values fall within the upper limit of normal or when patients come in into the file with A four values that are within the upper limit of normal, they are readily eligible for a JC down titration. So we have patients come in and there's a visit schedule that dictates when our A-four is to be drawn in on assessment of the A-four value, then the GC gets titrated down and changed or increased algorithm.

Speaker 2

Okay. All right. That's helpful. Thanks again for taking the questions.

Speaker 3

Thank you, John.

Operator

The next question is from Hartaj Singh with Oppenheimer. Please go ahead.

Speaker 9

Great. Thanks for the questions and really tough results to see today. Just a couple of questions. One was just going to, I guess, 3,205 study. What were the A 4 and GC reductions seen in the pediatric study?

Speaker 9

And then, were there any discontinuations in the 203 study? And then what were the reasons for that? And I got a quick follow-up.

Speaker 3

Hi, Hartaj. Thanks for your questions. We will be reporting the actual GC and A four reductions, I don't know, probably an upcoming medical conference later in the year for 205. So stay tuned on that. Regarding 203 discontinuations, the actual retention rate was actually quite high.

Speaker 3

We were able to achieve over 90% of patients completing the trial. Frankly, there was nothing related to safety matters that explain the discontinuations, personal reasons in a couple of adverse events that were deemed non related to study drug. I'll pass it on to Will if there's anything else to add.

Speaker 4

There were a handful of discontinuations, but there was really no pattern. There were as Javier said, there was no safety concern. There were personal issues like changing jobs or moving.

Speaker 9

Great. Thank you. And then just a couple of just questions on, if you did see reductions in A-four in 2 or 3, about how long did it take? And was that correlated with adequate drug levels in 203?

Speaker 3

Yes, that's a good question, Hartaj. So we didn't really see a correlation with time. We looked at week 4, week 8 and week 12. And frankly, the exposures were low throughout. We haven't yet we're in the process of examining an exposure response correlation.

Speaker 3

If there is one, they will be very weak because even the max exposure was meaningfully lower than the exposures that we achieved in 202 study where we saw a fairly strong signal on biomarker reduction both in ACTH, 17 hydroxyprogesterone-eighty four. So it's disappointing and I know that we hear as first trying to find explanations and find reasons as to why this happened. The current hypothesis of lesser compliance leading to lesser exposure of drug in my mind explains what's going on. And I want to make it very clear that we see a very different reality in 24 patients and that's why we believe that 24 study hopefully will read out different results.

Speaker 9

Yes, great, Javier. And my last question is just again going to 204, you said you might need a confirmatory Phase 3. That would be basically just like a 204. I mean, I guess these poorly controlled patients is not an area that you would look at further, right?

Speaker 3

Well, I think that upon unveiling the 204 study and upon looking at the totality of the 203 data, we'll develop a firmer point of view. But currently, our approach is to frankly pursue a broad indication for filgotastafone just like we have pursued so far, which includes adults and children. And frankly, there is a possibility that that study that we've been alluding to will include will be a study that includes both adults and children. We currently have a dose response study in 205 that's ongoing. It has because of safety, we wanted to expose 1st adults to 200 milligrams BID and then adults at 400 milligrams BID before we expose children to those doses, again to just make sure that the things were okay from that regard before we eventually the children.

Speaker 3

And I think that those 2 doses will be incredibly important as we design and think about that follow on study. So I think that there's still the possibility of us being able to address the more severe, the more difficult to treat patient population enrolled in 2 or 3.

Speaker 9

Yes. Javier, that makes a lot of sense. Thanks for the comprehensive answer and tough day today, but looking forward to more update.

Operator

The next question is from Evan Wong with Guggenheim Securities. Please go ahead.

Speaker 10

Hey guys, thanks for taking the question. I had

Speaker 5

a couple.

Speaker 10

I guess trying to understand some of the 203 dynamics a little bit more. Were you able to take a look at those maybe that were more compliant and better controlled if you were seeing a 4 that was more like the 2 zero two studies and whether the exposure there was more similar? And then in terms of the retroactive path forward and a potential Phase 3, can you expand a little bit more in terms of what the design could look like? It sounds like there could be a possibility of a different dosing regimen. Just wanted to confirm.

Speaker 2

I'll start there. I have a follow-up.

Speaker 3

Yes. Thanks, Evan, for the questions. I think we're in the process of really understanding our 2 or 3 day in-depth. The data that we released or the data that informs this release is frankly top line data. So we're in the process of conducting more analysis on the data.

Speaker 3

So stay tuned on that. In terms of Phase III design, frankly, will be dictated by the outcomes of the dose response arms that I mentioned in adults and in children. Those arms are currently ongoing. And also the results of the 204 study, I don't discard at this stage that we might need a higher dose and possibly a BID dose of telesophan to address this more severe, more difficult to treat patient populations. But that will depend on the data that we see.

Speaker 3

Like I said earlier, our intent is to bring forward the 205 and 204 study results to the FDA, hold an end of Phase 2 meeting and that time propose a development program that makes sense for both development piece. You said you had a follow on question, Evan?

Speaker 10

Yes. Just wondering with the cost savings initiatives and cash runway, I guess, does that looking at both for the development of adult and pediatrics? Or is there kind of prioritization of maybe one first?

Speaker 3

Yes. I'll let Sunil take on my question.

Speaker 1

Yes. Hey, Evan. Thanks for taking the time to join us today. So our current operating plan contemplates sort of the scenario of events that Javier has outlined, which is reading out the 204 study, garnering additional dose ranging data from the 205 study, taking that to an end of Phase 2 and commencing assuming positive results from both studies, a single Phase 3 study in both populations. So when you look at our new extended current cash runway, those assumptions and plans are contemplated in those estimates.

Speaker 2

Thanks guys.

Operator

The next question is from Aidan Husainoff with Ladenburg. Please go ahead.

Speaker 8

Good afternoon, everyone. Thank you for taking the questions. So a couple. So neurocurrent will likely launch the drug in 2025 in both pediatric and adult population. So if you are on Phase 3, how do you plan to enroll these patients given the prior challenges in the Phase 2 enrollment?

Speaker 3

Hi, Aidan. This is Javier. Thanks for the question. I think that frankly, we've I know that our competition is intending to launch or at least express a desire to launch in 2025. The 'twenty five, I think that we still need to learn about more about their data, more about the regulatory pathway and details about the launch.

Speaker 3

I feel that launches are typically not especially early on in for rare diseases are not global launches. So there might be regions and areas of the world where the studies can be conducted. Adoption of therapy probably won't be will be 12. There will be an element of patients that will qualify for the Neurocrine drug and those might be eligible patients to come into a trial. So I think it's going to have we're going to have to wait and see.

Speaker 3

I think that our studies, all of them 203, 204, 205 ended up being oversubscribed with very strong patient interest. And frankly, the results of 204 and 205 will frankly dictate the appetite of patients to be part of our program. We'll definitely make it I think part of competitive landscapes and have had to enroll clinical trials in the past where a competitor has been approved and that often creates the right momentum for patient participation into research.

Speaker 8

And Javier, do you think the FDA will be selective in terms of the potential specific label indicating the baseline GC levels?

Speaker 3

Are you referring to GC levels in the context of 204 potentially?

Speaker 8

I'm referring to the potential conisopant approval. Do you think they will be specific in terms of the GC levels or they will be broad?

Speaker 3

Yes. I don't really have frankly maturation into what Neurocrine will do or what frankly what the FDA will do. My response will be speculative, so rather not do that.

Speaker 8

Okay, understood. And the last one, could you share any changes in the characteristics additional characteristic in total 3 studies such as 17 OHP or OCTH levels in total 3 study?

Speaker 3

Sure. I will pass on that question to Doctor. Woodruff. So andersen Dion or

Speaker 4

A four is the most reliable of the biomarkers that we have in JH. So that's our primary. But both ACTH and 17 OHP were dramatically elevated relative to in 203 relative to 204. So the 17 OHP, for example, in 203 was more than 80 times the upper limit of normal compared to 204 which was 28 times upper limit of normal. Important to keep in mind that 28 times sounds high, but actually if you the treatment goal is never to normalize 17 OHP.

Speaker 4

In fact, you want to be several fold above normal to be in what's considered the appropriate range. So just for a little context. And similarly with ACTH, in 203 it was close to 7 times ever limit of normal. And in 204 it was pretty close to normal. So that's a it's a meaningful difference that carries it over across all the biomarkers in a consistent way.

Speaker 8

Understood. Thanks so much. Thank you for taking questions.

Operator

The next question is a follow-up from John Wollobin with JMP Securities. Please go ahead.

Speaker 2

Hey, Sameer. Thanks for taking the follow-up. You mentioned the 202 data a few times and there you had pretty high baseline levels of A four as well and you mentioned that the exposures was greater, but that was a 400 milligram dose. So can you talk a little bit about what you know about the 400 milligram versus the 200 milligram exposure levels if patients do take the drug as intended?

Speaker 3

Yes. Hi, John. It's Javier. So the exposures in 202 were clearly greater between 2 and 3 fold exposures we've seen in the 203 study. And it is our current hypothesis that delta in exposures explain away the current effect sizes that we saw in 203, which are very different than the effect sizes we saw in 202.

Speaker 3

I completely agree with you that the exposures in 202 are greater because one possibility is not just because the drug is greater, but also because compliance rates in 202 or greater. I mean over 95% of patients took 100% of their study drug in 202. Again, a smaller study, more manageable, lesser sites, less complexity probably. So at this stage is really difficult to attribute whether the effect is solely compliance or solely exposures. What I can tell you is that there was a meaningful delta between 203 and 204 sorry, 202 and 203 exposures.

Speaker 3

And there was a real separation between effect sizes in the two studies. And so that's frankly all we know. I mean, I can tell you that if we would have achieved the speculation is that if we would have achieved exposures seen in 202 with in the 203 study, we think that we would have seen the same effect sizes given that the patient population was very similar. As you said, A four values were comparable between the two studies and GCUs was comparable. The major difference between the 202 and 203 was the age group of the study participants in the control group in 202, which was around 42 and the 2 or 3 study, which is on average 32 years of age.

Speaker 2

Okay. That's very helpful context. Thanks again, Javier.

Operator

Ladies and gentlemen, thank you for your participation. This concludes today's teleconference. You may disconnect your lines at this time and have a nice day.

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Earnings Conference Call
Spruce Biosciences Q4 2023
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