Earnings call transcript: Silence Therapeutics sees stock rise post-earnings

Silence Therapeutics PLC (SLN) experienced a notable premarket stock price increase of 5.24%, following its earnings call for the fiscal year 2024. The company’s strategic collaborations and promising pipeline developments were highlighted as key drivers of its financial performance. The stock closed at $4.77, with a premarket price of $5.02, reflecting investor optimism. According to InvestingPro data, this comes after a challenging period where the stock has fallen over 81% in the past year, with analysts setting price targets ranging from $6 to $75.

Key Takeaways

• Silence Therapeutics’ premarket stock rose by 5.24%.
• Revenue increased to $43.3 million in 2024 from $31.6 million in 2023.
• Strategic collaborations with AstraZeneca (NASDAQ:AZN) and Hanseo Pharma boosted revenue.
• Promising developments in siRNA therapies for rare diseases.
• Cash reserves extended runway into 2027.

Company Performance

Silence Therapeutics reported a robust increase in revenue for 2024, attributed primarily to strategic partnerships and advancements in its therapeutic pipeline. The company has focused on rare diseases and cardiovascular conditions, setting itself apart with its proprietary siRNA platforms. While the firm managed to reduce its net operating loss, InvestingPro analysis indicates the company maintains strong liquidity with a current ratio of 9.31, though it’s currently burning through cash reserves. The platform offers 10 additional key insights about SLN’s financial health, available with a subscription.

Financial Highlights

• Revenue: $43.3 million in 2024, up from $31.6 million in 2023.
• Net Operating Loss: $63.3 million in 2024, compared to $64.4 million in 2023.
• Net Loss: $45.3 million in 2024, down from $54.2 million in 2023.
• Cash and Equivalents: $147.3 million as of December 2024.

Market Reaction

The company’s stock saw a 5.24% increase in premarket trading, reflecting investor confidence in its strategic direction and potential for future growth. The stock’s movement is significant, considering its 52-week low of $4.06. Based on InvestingPro’s Fair Value analysis, the stock appears undervalued at current levels, though investors should note the company’s Financial Health Score of 2.19, rated as ’FAIR’ by InvestingPro’s comprehensive evaluation system.

Outlook & Guidance

Silence Therapeutics has outlined a promising outlook, with plans to secure a partner for its Phase 3 study of Zolaciran and ongoing discussions for Divisiran applications in other conditions. The company anticipates completing enrollment for Divisiran Phase 2 by year-end and is preparing for a Phase 1 study of SLN-548 in the second half of 2024.

Executive Commentary

Craig Toomin, CEO, emphasized the company’s commitment to advancing its siRNA therapies, stating, "The Cylance team remains very, very focused on executing to deliver life-changing sRNA therapies to patients in need." Steven Romano, Chief R&D Officer, highlighted potential new applications for Divisiran, saying, "We’re looking at that. And HH is one of those courses."

Risks and Challenges

• Securing partnerships for Phase 3 studies remains a critical challenge.
• The competitive landscape in cardiovascular and rare disease therapeutics.
• Regulatory hurdles in advancing clinical trials to later stages.
• Dependence on strategic collaborations for revenue growth.
• Market volatility affecting stock performance.

Q&A

During the earnings call, analysts inquired about the timeline for securing a partner for Zolaciran and potential new indications for Divisiran. The management expressed optimism about ongoing discussions and highlighted positive regulatory feedback for upcoming trials.

Full transcript - Silence Therapeutics PLC (SLN) Q4 2024:

Conference Operator: Good day and thank you for standing by. Welcome to the Cylance Therapeutics Fourth Quarter and Full Year twenty twenty four Conference Call. At this time, all participants are in listen only mode.

After the speakers’ presentation, there will be a question and answer Please be advised that today’s conference is being recorded. I would like to hand the conference over to your first speaker today, Jem Hawkins (NASDAQ:HWKN), Head of Investor Relations and Corporate Communications. Please go ahead.

Jen Hopkins, Vice President of Investor Relations and Corporate Communications, Cylance Therapeutics: Good morning and good afternoon, everyone. Thank you for joining us today. My name is Jen Hopkins, Vice President of Investor Relations and Corporate Communications at Cylance. Joining me on today’s call are Craig Toomin, our President and CEO, who will provide an update on the business Rhonda Helms, our Chief Financial Officer, who will review our financial performance and Steven Romano, our Chief R and D Officer, who will provide a clinical update. For those of you participating via conference call, the accompanying slides can be accessed by going to the Investors section of our corporate website at www.silencetherapeutics.com.

I’d like to remind you that during today’s call, management will make projections or other forward looking statements regarding anticipated future events or the future financial performance of the company, including clinical development, timing and objectives, the therapeutic potential of our product candidates, our operational plans and strategies, anticipated milestone payments, anticipated operating and capital expenditures, business prospects and projected cash runway. Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in our most recent annual report on file with the SEC and any future filings. In addition, any forward looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views at any subsequent date. We specifically disclaim any obligation to update such statements. With that, I’d like to turn the call over to Craig.

Craig?

Craig Toomin, President and CEO, Cylance Therapeutics: Thank you, Jim, and thanks everyone for joining today’s webcast. I’m pleased to be with you today to discuss our 2024 full year performance and share some color on what’s ahead for the company. I’ll start by quickly touching on a few key highlights about our full year performance. Starting with zerlacerone, our SRNA for high LP delay. The ALPHAQR three sixty Phase two study of zerlacerone and ASCVD patients with high LP delay delivered positive results that were featured in a late breaker at and published in JAMA.

The study showed Lp Li reductions exceeded 90%, effects were durable and zolazarone was observed to be well tolerated. These data support a competitive profile that we believe can be further defined in Phase three. The silos team supported by top cardiologists have done an outstanding job designing what we are confident is a highly differentiated Phase three program for zolazarone. We recently met with global regulatory agencies on the design and received very positive feedback across the board. The SILENCE team has also been successfully executing on core readiness activities for Phase III development, including manufacturing readiness.

Turning to divestiran, our first in class sRNA for polycythemia vera. The Sanricos Phase one study of divestiran delivered positive results that exceeded our expectations. Data were highlighted at ASH and showed divvesterone completely eliminated the need for phlebotomy in all well controlled patients. The safety and tolerability profile continues to look very favorable. In addition, we started dosing patients in the Sanrico Phase two study and the European Commission granted diveseron orphan drug designation for PV.

As a reminder, diveseron also has FDA Fast Track and orphan drug designations for PV. In terms of other pipeline advancements, we are pleased to have our third SRNA from our gold platform enter the clinic in 2024 under our AstraZeneca collaboration. We value this partnership very much and are proud of the program we were able to advance together. We look forward to its further progress and the potential to earn additional milestones. We also progressed several preclinical sRNA candidates for hepatic targets.

Turning to Slide five and what’s next for our company. This morning, we announced that in 2025, we are prioritizing investment in programs targeting rare conditions where we believe we can deliver on clear unmet needs with first in class and or best in class sRNAs. Divesiran is a great example of that. We remain confident in our zolazarone program for high LP delay and believe we have very differentiated design for our Phase three program. However, today, we are making clear that we will only initiate the Phase three outcome study once a partner is secured.

This strengthens our cash position into 2027 and gives us flexibility to invest in our innovative pipeline, while we continue partnering discussions for Xelaciran. We have listened very carefully to our shareholders and made this decision with their collective feedback in mind. I want to reiterate that we continue to believe strongly in Xelaciran’s potential. There are very few cardiovascular assets in development that aim to treat an unmet medical condition as large as the LP LILA opportunity. We are hopeful we will secure the right partner to bring this very promising program forward.

Until a partner is secured, we do not plan to provide any further updates. Turning now to divestiram. We announced this morning that we completed follow-up in the Phase one portion of Sanrico this month and look forward to presenting more data from that study at medical meetings this year. The outstanding data from the Sanrico Phase one study have generated a lot of excitement from the medical community and patients who want to be involved with the program. In fact, we also announced this morning that we anticipate full enrollment in the Sanrico Phase two study by the end of this year.

While we are currently focused on the PV indication for divisiran, we continue to believe it has broader therapeutic potential. Given the outstanding PV results we have seen in Phase one, we are planning an investor event later this year and look forward to discussing the program in more detail then. In addition to divestiran, we were pleased to announce today that we plan to start a Phase one study of SLN-five 48, our wholly owned sRNA targeting complement factor B in the second half of this year. Steve will go into a bit more detail on this in a few minutes. In terms of what’s next for our gold platform, we have multiple undisclosed programs that have generated encouraging preclinical data.

This includes the three targets that we’ve retained global rights to following the conclusion of the Hanseo Pharma collaboration we announced this morning. We are evaluating these programs as part of our broader portfolio and will determine which ones we want to bring forward ourselves or potentially partner. As I mentioned, we will be prioritizing targets in rare conditions where we believe we can deliver valuable competitive profiles to address patient needs. In addition, we plan to invest selectively in our extra hepatic work where we are seeing promising early data from programs targeting multiple cell types. We look forward to sharing more as we move ahead in these data mature.

With that, I will now turn the call over to Rhonda to review our 2024 financial performance and guidance for 2025. Rhonda?

Rhonda Helms, Chief Financial Officer, Cylance Therapeutics: Thank you, Craig. First, I would like to point out that effective 01/01/2025, Cylance has transitioned from a foreign private issuer to a U. S. Domestic issuer, which requires us to comply with The U. S.

Domestic reporting requirements under the Exchange Act. We are now required to file periodic reports and registration statements on U. S. Domestic issuer forms with the SEC in accordance with U. S.

GAAP as opposed to IFRS and in U. S. Dollars versus British pound. Now let me turn to the financials. For the year ended 12/31/2024, the company recorded $43,300,000 in revenues versus $31,600,000 in 2023.

The increase of $11,700,000 is largely due to the collaboration arrangements we have entered for development of candidates utilizing our siRNA platform. As Craig mentioned, our AstraZeneca collaboration continues to advance nicely, and we are hopeful that this program will continue to move forward and allow us to receive additional milestones. Turning to the Honto Pharma collaboration, we announced this morning that Honto opted not to pursue further development under our collaboration. As a reminder, this was a collaboration to develop siRNAs using our gold platform for three undisclosed preclinical liver targets. Hanse formerly had options to license China region rights on two of the targets and global rights on the third target.

As a reminder, we record revenue from our collaborations based on percentage of contract completion. Therefore, in 2024, we recognized $24,600,000 resulting from a cumulative catch up following the completion of all required obligations to Hanseo under the collaboration. Finally, during 2024, we recorded the remaining royalty revenue from an ILM of approximately $144,000 The expenses related to our partner program, including the portion of our employees’ time dedicated to these programs, are recorded as cost of sales as they are attributable to the revenues. These expenses were $11,800,000 in 2024 compared to $12,900,000 in 2023. As expected, R and D costs rose in 2024 to $67,900,000 versus $56,900,000 in 2023.

This increase was primarily due to advancing our proprietary zolasterin and diviscerin programs, which Craig previously mentioned. We also strategically invested in further development of our platform and identifying new targets to further expand our proprietary pipeline. General and administrative costs were $26,900,000 in 2024 versus $26,200,000 in 2023. The increase was primarily as a result of additional legal and accounting expenses required to transition to filing as a U. S.

Domestic issuer, including our transition to U. S. GAAP. The company’s net operating loss for the full year of 2024 was approximately $63,300,000 versus $64,400,000 in 2023. The decrease in our net loss is due to the increase in revenue, partially offset by the increase in R and D costs as a result of advancing our programs in clinical development.

We reported other income of approximately $4,500,000 which largely represents the accretion of our U. S. Treasury bill compared to $1,800,000 in 2023. We also reported approximately $13,700,000 from the benefit of our R and D tax credit in The UK compared to $11,900,000 in 2023. The company’s net loss for the full year of 2024 was approximately $45,300,000 versus $54,200,000 in 2023.

The company’s cash, cash equivalents and short term investments were $147,300,000 at the December. This includes cash and cash equivalents of $121,300,000 and short term investments of $26,000,000 Turning to Slide eight and the 2025 cash guidance. As Craig mentioned, we have made the decision only to initiate the zolaziran Phase III outcome study once we have secured a partner. This allows us to extend our projected runway into 2027. I’ll echo Craig’s comments that we are prioritizing programs targeting rare conditions where we see the opportunity to deliver on clear unmet needs with innovative siRNA therapies.

This includes sevistran for TB, which remains a top priority. In addition, we look forward to advancing additional programs in our pipeline, including our extrahepatic work. With that, I’ll turn the call over to Steve for a clinical update. Steve?

Steven Romano, Chief R&D Officer, Cylance Therapeutics: Thanks, Rhonda. As Craig mentioned, we made great progress advancing Doviscerin, a first in class sRNA for PV in 2024. The Senrico Phase one results were impressive and have garnered enthusiasm for the program. The Phase two study is enrolling very nicely and as Craig mentioned, we anticipate full enrollment by the end of this year. As a reminder, TB is a rare myeloproliferative neoplasm, a type of blood cancer that is associated with erythrocytosis or an increase in the production of red blood cells.

Other blood cell types, including WBCs and platelets may also be increased. The increase in RBC mass corresponding to a substantial elevation of somaticrete leads to a higher incidence of thrombotic or clotting events and an increase in adverse CV outcomes. TB is associated with a range of burdensome symptoms, including fatigue, cognitive disturbance and pruritus and additionally, longer term can transform to myelofibrosis and acute myeloid leukemia. PV impacts around one hundred and fifty thousand individuals in The U. S.

And three point five million worldwide. The aim of the treatment is to maintain Imadocrit less than forty five percent, a level that is associated with a reduced incidence of thrombosis and CV associated death. Treatment usually requires routine phlebotomy along with a low dose aspirin. Many patients regardless of risk level require the addition of cytoreductive agents to ensure achievement of treatment goals. Phlebotomy, while helpful, is time consuming, may not maintain patients at safer hematocrit levels consistently and can contribute to iron deficiency and overall symptom burden.

At the bottom of this slide, we have a quote from Nona, who is living with PV. She says, the PV aspect means that you have to have phlebotomies regularly, and I think the most crippling thing about that is the fatigue. We are hopeful based on the San Diego Phase one data that deViscerin has the potential to greatly reduce and even eliminate the need for phlebotomy. Turning to Slide 12 of diviscerin, a first in class sRNA for PV, I’ll quickly review how diviscerin works for those less familiar. TMPRSS6 is a negative regulator of hepcidin, the body’s master regulator of iron metabolism, including its absorption, distribution and storage.

The therapeutic hypothesis for the use of divisiran in PV patients is the following: By silencing TMPRSS6, hepcidin production and released by liver hepatocytes will increase, leading to the restriction of iron to the bone marrow and thus reducing the excessive production of red blood cells, a process dependent on availability of iron. Turning to the Sanrico Phase one study, the design was open label with three cohorts and enrolled 21 PV patients. We tested doses of three, six and nine milligrams per kilogram consisting of six, eight and seven patients respectively. All patients were scheduled to receive four doses at six week intervals and then were followed for sixteen additional weeks for a combined total of thirty four weeks of treatment and follow-up. Key inclusion criteria for the trial subjects included a diagnosis of PV based on WHO criteria and a history of requiring a minimum of three phlebotomies in the previous six months or five phlebotomies in the previous twelve months.

Patients on stable doses of cytoreductive agents were allowed and given the exploratory nature of the Phase one study, both well controlled patients that is those with hematocrits forty five percent or less and those less well controlled with hematocrits greater than forty five percent were included. As Greg mentioned, all patients completed the follow-up period this month and the Phase one study is now complete. The data slides I’m about to show you are from the ASH presentation in December and include 19 PB patients with a combined history of seventy nine phlebotomies in the six months prior to enrollment. You can see historic phlebotomy details are in orange shades to the left of center and capture all events up to day one, the time of the first dose administration. To the right of center in blue shades are any phlebotomies recorded during the trial, both the treatment period as well as the follow-up period.

No patients entering the trial with well controlled hematocrit levels required a phlebotomy. In other words, one hundred percent of this group maintained adequate control of hematocrit as per treatment guidelines. Only five phlebotomies occurred during the treatment period, all were in patients who entered the study with high baseline hematocrit levels, those over forty five percent. Two phlebotomies occurred in the sixteen week follow-up period following the last administered dose. In fact, no patient with hematocrit less than 50 at baseline required a phlebotomy during the treatment period.

These data are very promising. Given the fact that we included a range of patients in this trial regardless of baseline hematocrit, it’s important to evaluate the effect of diviscerin on both well controlled patients, again, those with hematocrit levels less than or equal to 45% as well as those with high baseline hematocrit levels. You can see here that diviscerin reduced hematocrit levels in all patients regardless of baseline levels. The eviscerin also demonstrated robust target engagement. You can see here we observed early and sustained hepcidin elevation.

Importantly, these elevations are within the physiologic range of hepcidin levels. Importantly, deviserin was safe, well tolerated, all doses tested. Majority of treatment emergent adverse events were mild, none over grade two. There were no treatment related serious adverse events or TAEAEs leading to discontinuation. So in summary, the Phase one data showed that Favissorin eliminated the need for phlebotomy in all well controlled patients, lower hematocrit levels in all patients regardless of baseline levels and the safety tolerability profile continues to look very favorable.

We look forward to presenting additional Phase one data at medical congresses this year. Here’s a high level look at the design for the ongoing Phase two portion of Sanrico. This is a randomized double blind study evaluating diviscerin in up to 40 PV patients. Unlike the Phase one, where we allow patients to enter with a range of baseline hematocrit levels, all patients entering the Phase two will have a hematocrit level below 45%. The study is thirty six weeks and we are assessing two different dose levels and regimens.

The primary endpoint is the percent of patients with hematocrit at or below forty five percent without the need for phlebotomies. We will also be assessing the effect of Devisiran in improving PD related symptoms. As we mentioned, the study is enrolling nicely and we anticipate full enrollment by the end of this year. Turning now to SLN-five forty eight, our wholly owned siRNA targeting complement factor B. The complement system is a critical component of the innate immune system and is made up of several dozen liver derived proteins and protein fragments.

It complements the ability of antibodies and phagocytic cells to rid the body of foreign microbes as well as help clear cellular debris, including damaged cells. It plays an important role in inflammation. There are three distinct biochemical pathways that can lead to activation of the complement cascade and include the classical, alternative and lectin pathways. Importantly, both deficiencies and over activation of the complement system play a role in a broad range of conditions with immune components. Given the complexity of the complement system pathways and large number of proteins involved, there are a plethora of potential targets for therapeutic intervention.

SLN-five 48 is an siRNA targeting complement factor B and could potentially play a therapeutic role in conditions associated with over activation of this pathway, including complement mediated renal diseases among others. The long acting profile of our gold platform compounds could allow for the development of an infrequently dosed therapeutic option. We’re excited to advance this compound into first in human study in healthy volunteers later this year. This slide is a brief summary of the Phase one study design. It is a randomized double blind placebo controlled single ascending dose study that plans to enroll up to 32 healthy volunteers across four dose cohorts.

The primary objective is to evaluate the safety and tolerability of SLN-five forty eight in healthy subjects as well as the pharmacokinetic and pharmacodynamic profile, It incorporates sentinel dosing and all patients will be vaccinated and receive prophylactic antibiotics as appropriate. We look forward to sharing more details about this program, including our development strategy at a future time. As Craig mentioned, we anticipate starting the study in the second half of this year. With that, I’ll turn the call back over to Craig.

Craig Toomin, President and CEO, Cylance Therapeutics: Thanks, Steve. In summary, our decision to only initiate the Phase three outcome study of zolazarone once we’ve secured a partner extends our projected cash runway into 2027. This gives us flexibility to invest in our innovative pipeline while we continue partnering discussions. We remain confident in zerlaceron and will provide an update when there is one. On this slide, you can see our anticipated clinical milestones for 2025.

For divisoron, we completed follow-up in the Phase one Sanrico study this month and will present additional data at the medical meetings this year. We anticipate full enrollment in the Phase two Sanrico PD study by year end. We are also planning to host a diveseron focused event later this year. So stay tuned for more information on that. For FLN-five forty eight, we are planning to start the Phase one study in healthy volunteers in the second half of this year.

We’re also looking forward to progressing our extra hepatic work and sharing these data at the appropriate time. The Cylance team remains very, very focused on executing to deliver life changing sRNA therapies to patients in need. With that, I’ll pass back over to the operator for your questions.

Conference Operator: Thank you. Our first question comes from the line of Mike Ulz of Morgan Stanley (NYSE:MS). Your line is now open.

Mike Ulz, Analyst, Morgan Stanley: Good morning and thanks for taking the question. Maybe just one focused on zerlaciran. I guess to the extent you can, if you could provide some color on partnership discussions? And then just how important is the horizon data to those discussions, which we’re expecting, I guess, in first half of next year now? And then maybe secondly, just talk about some of the types of partnership structures you’re considering?

Thanks.

Craig Toomin, President and CEO, Cylance Therapeutics: Thanks, Mike. We’re not going to comment specifically on ongoing partnership discussions today, but it is interesting to note that since the recent shift in the timing of the horizon readout, companies including Novartis (SIX:NOVN) have pledged more funding for LPD L A studies. So interesting phenomenon. Look, we’re not a one product company. We’ve got a portfolio of assets with great potential.

And as you know, divestron is a great example of that. And it is a fine balance to kind of manage the resources amongst the products. And we want to make sure we get the best returns. So that’s our announcements today. Cylance has really done an excellent job.

I give us all the team all full credit for getting zerolaciran to this point, which is designing this highly differentiated Phase III program. We continue to believe in its high value potential, very competitive profile, substantial market potential that we’ve talked about in multiple occasions. And we are actively engaged. So I will say that we remain actively engaged in partnering discussions and hopeful we’ll be able to secure the right partner to bring this very promising program forward, both in development and commercially. So I won’t say more on that, but we will update you if there’s something to update you on regarding a partner.

Mike Ulz, Analyst, Morgan Stanley: Great. Thank you.

Conference Operator: Thank you. One moment for our next question. Our next question comes from the line of Kostas Pilaris of BMO Capital Markets. Your line is now open.

Kostas Pilaris, Analyst, BMO Capital Markets: Hello, everyone. Good morning. Thanks for taking our questions. Maybe one question on Zevlaziran and one on DIVEZEDARAN from us. How ready are you for the Phase three trial?

And specifically, from the time you secure a partner, how fast do you think we can start the Phase three? And will the partner be able to potentially make changes to the Phase three design? Or do you think the Phase three design is set and the partner needs to kind of agree to that? And the second question on divestiran is, would you consider evaluating divestiramine hereditary hemochromatosis given the relevance of the target there? Thank you.

Craig Toomin, President and CEO, Cylance Therapeutics: So we are in a logistical phase. We’re wrapping up Phase III readiness activities, which are on track to complete by mid year. So we’re in a little bit of a period where we can make some fine tuning if we needed to do that with a partner. But we’ve advanced very, very nicely across the team in order to be prepared, including, as I mentioned, manufacturing preparedness, which is very important. So there is some time, a bit of time before the track that we had outlined before really gets more fixed, if you will.

In terms of HH, Steve, do you want to comment on HH?

Steven Romano, Chief R&D Officer, Cylance Therapeutics: Yes, sure, Costa. So yes, we’re certainly obviously focused on the PV program and executing that. But we do know because of our mechanism that implies actually across a fairly broad range of conditions where hepcidin may play a role or manipulating that cytin pathway may play a role therapeutically. So we’re looking at that. And HH is one of those course.

So we haven’t declared any additional work specifically with regards to trial work, but we’re examining the opportunity to expand our program.

Kostas Pilaris, Analyst, BMO Capital Markets: Thanks very much.

Conference Operator: Thank you. One moment for our next question. Our next question comes from the line of Richard Law of Goldman Sachs. Your line is now open. Thanks.

Good morning, everyone. So a couple of questions for me. What is the goal for deviseran regarding differentiation? Can you differentiate clinically from buspiratide besides dosing frequency? And also, what are the biggest hurdles that you see for partnering selglyceran?

Thanks.

Craig Toomin, President and CEO, Cylance Therapeutics: Steve, do you want to take differentiation, Eviscerin?

Steven Romano, Chief R&D Officer, Cylance Therapeutics: Yes. So first of all, we want to be the first siRNA to the market for PV. So we’re very excited about that opportunity. And clearly, and I wouldn’t minimize it, one of the major differentiations, of course is going to be the infrequency of dosing. And in fact, as I mentioned, as we move forward into completion of the Phase II, we may have an idea of even less frequently dose regimen versus what we evaluate in Phase The other things we’ll look for obviously are symptomatic improvement, etcetera.

So we’ll look across the range of important dimensions to measure outcome in this disease. But until those that work is done, it’s hard to say what point of differentiation or points of differentiation will be available. But the bottom line is the convenience factor is going to be a very important one. And we hope that that long term effect could have an impact on the likelihood that patients maintain hematocrit at levels that are safe and below 45 consistently. So more to come on that as the profile of the drug is known.

Craig Toomin, President and CEO, Cylance Therapeutics: In terms of partnering and hurdles, really no single item for the parties is different for every one that we’ve had dialogue with. The dialogues do tend to be a little bit around the notion of business strategy and recognition and intrigue in that very large market opportunity. So we remain very confident in the programs we discussed. The dialogues continue and we will pursue that. As you know, partnerships often don’t really happen on a clock.

It involves coincidence and needs and timing amongst the parties. But we are very active, I can tell you that. And thank you for the question.

Myles Mentor, Analyst, William Blair: Yes, thank you.

Conference Operator: Thank you. One moment for our next question. Our next question comes from the line of Key Naki of Tardan. Your line is now open. Yes, thanks.

A question about the candidates being developed for HANTSO. Is there anything there worth continuing to pursue on your own? Or how do we view the status of that?

Craig Toomin, President and CEO, Cylance Therapeutics: Yes. Thank you. We’re very interested in the programs that we have been developing in that productive partnership. We have seen and continue to see encouraging preclinical data in each of the programs. Now we will actually retrieve those programs and have the opportunity either to develop them ourselves or potentially partner or license.

So it actually gives us the control to determine what we want to do with those, but obviously in the context of having good data. I don’t know, Rhonda, if you want to reiterate a little bit of the financials on that because it’s not abundantly clear perhaps.

Rhonda Helms, Chief Financial Officer, Cylance Therapeutics: Yes, sure. So as I mentioned, the revenue did show the cumulative catch up. So because we have no further obligation in our collaboration, all the original upfront milestones are basically recognized at the end of the year. So we don’t anticipate further from HONTHO. However, we will continue to have revenue from AstraZeneca as that program continues.

And then all the other additional new targets from the AstraZeneca collaboration could potentially add some revenue to that as well.

Kostas Pilaris, Analyst, BMO Capital Markets: Okay. Thank you.

Conference Operator: Thank you. One moment for our next question. Our next question comes from the line of Myles Mentor of William Blair. Your line is now open.

Myles Mentor, Analyst, William Blair: Hi, everyone. Thanks for taking the questions. First one on zelaciran. Just In your regulatory discussions, did you actually propose a dose to take forward into that Phase three? I know you said three hundred milligrams previously, but you have not associated a frequency with that.

That’s the first one. Second is, I take a lot of questions about how a five to ten nanomole per liter increase in hepcidin that you get with divisiran actually confers the efficacy you’re seeing when Russetite theoretically gets much higher than that. So maybe you can talk about the difference between the endogenous trigger that you’re getting with TMPRSS6 inhibition and maybe the safety ramifications between that and giving a hepcidomimetic in PV, that would be helpful. Thanks very much.

Craig Toomin, President and CEO, Cylance Therapeutics: Steve, both of those for you.

Steven Romano, Chief R&D Officer, Cylance Therapeutics: Yes. Well, yes. So the question is with regards to the differences in a way of intervening on the pathway, the epsilon pathway. So yes, obviously, Russetrotide is an exogenously administered hormone. So naturally, it’s not a surprise that you typically get larger exposures based on that.

Ours is manipulating the pathophysiology, the underlying physiology and increasing the internal production of hepcidin. It’s less important the level as we’ve already learned in Phase one than the correlation with that increase on clinical benefit. And what we see very clearly as we’ve shown you is with that increase in hepcidin within the physiological range, which by the way is 20 to 40 fold higher than the baseline of these patients who come in, in our Phase one study with very low levels of peptidin is corresponding, it appears, correlating with robust outcome, which is a reduction in the need for phlebotomy and the maintenance of Hematocrit. So that is very, very clear that we’re getting the intended effect clinically, which is in fact the registrable endpoints for this program and other programs. And we’re doing that by increasing hepcidin within levels of the physiological range, but much above the baselines.

So I think that’s very important.

Craig Toomin, President and CEO, Cylance Therapeutics: In terms of those frequency in the agency deliberations.

Steven Romano, Chief R&D Officer, Cylance Therapeutics: Yes. But I should also add that the safety because you asked about safety and we cannot really comment comparatively on safety until you actually conduct your program. And even then it’s going to be cross program comparisons. We want to be very careful about that. But clearly, our compound is very safe, what we’re seeing in Phase one and what we are beginning to see in Phase two is a very safe profile.

Okay. And with regards to the interactions with the agency around the I think the question was around zerolaciran and we have talked to the agency naturally about what we believe is a the reasonable dose, I should say the optimal dose and frequency. This is a very competitive space, so we’re not sharing that information at this point. But obviously when you talk to regulators about a Phase three program, you need to be pretty confident about the decisions you’re making. I’ll leave it at that.

Craig Toomin, President and CEO, Cylance Therapeutics: And as also further advised obviously our Phase three planning and design. Thank you.

Myles Mentor, Analyst, William Blair: Makes sense. Thanks for the questions.

Conference Operator: Thank you. Thank you. I’m showing no further questions at this time. I would now like to turn it back to Craig Thumann for closing remarks.

Craig Toomin, President and CEO, Cylance Therapeutics: Just want to thank you all for joining us on today’s call. We really look forward to keeping you updated on our progress, very excited about the opportunities in front of us and have a great day.

Conference Operator: Thank you for your participation in today’s conference. This does conclude the program. You may now disconnect.

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