Vanda Pharmaceuticals - Earnings Call - Q4 2024

Executive Summary

• Q4 2024 revenue rose 17% year over year to $53.2M and 12% sequentially; Fanapt drove growth (+18% YoY to $26.6M), while HETLIOZ declined 5% YoY; PONVORY grew 11% q/q.
• Reported diluted EPS was -$0.08 (vs -$0.04 YoY; -$0.09 in Q3), as operating expenses rose with Fanapt/PONVORY launches; net loss improved q/q to -$4.9M from -$5.3M.
• 2025 revenue guidance: $210–$250M; management highlighted potential headwinds from Medicare Part D benefit redesign on gross-to-net, Fanapt wholesaler inventory normalization, and Q1 plan transitions.
• Pipeline/regulatory catalysts: tradipitant NDA (motion sickness) filed; Bysanti (milsaperidone) NDA for bipolar I and schizophrenia expected in Q1 2025; imsidolimab BLA in 2025; DTC for Fanapt began January 2025; psychiatry portfolio target >$750M by 2030; total company >$1B.

What Went Well and What Went Wrong

• What Went Well

  • Fanapt momentum: NBRx grew >160% YoY in Q4; Fanapt sales +18% YoY and +11% q/q; TRx +~9% YoY; inventory at wholesalers just above 4 weeks, indicating healthy demand and stocking.
  • PONVORY execution: Net sales +11% q/q as channel destocking from Q3 normalized; specialty sales force ramping and prescriber programs expanded >4x q/q in Q4.
  • Strategic pipeline progress: Tradipitant NDA (motion sickness) submitted; Bysanti NDA imminent; Fanapt LAI Phase 3 initiated; imsidolimab licensed with BLA planned 2025; EMA submissions for Fanapt/HETLIOZ.
  • CEO tone: “Strong revenue growth for Fanapt is putting us on a significant growth trajectory for 2025 and beyond...”.

• What Went Wrong

  • HETLIOZ pressure: Q4 sales -5% YoY (12% q/q rebound), with ongoing generic competition, variable specialty pharmacy inventory dynamics, and potential future declines.
  • Expense intensity: Operating expenses rose to $63.5M (vs $52.4M YoY; $58.7M in Q3) on commercial buildout and legal/corporate items; net loss widened YoY.
  • Near-term gross-to-net headwinds: 2025 Medicare benefit redesign expected to negatively impact Fanapt/HETLIOZ (Medicare segment), plus possible Q1 wholesaler destocking and insurance transitions.

Transcript

Operator (participant)

Hello and thank you for standing by. At this time I would like to welcome you to the Q4 2024 Vanda Pharmaceuticals earnings conference call. All lines have been placed on mute to prevent any background noise. After the speaker remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. I would now like to turn the conference over to Mr. Kevin Moran, Vanda's Chief Financial Officer. Please go ahead, sir.

Kevin Moran (CFO)

Thank you, Jericho. Good afternoon, and thank you for joining us to discuss Vanda Pharmaceuticals' fourth quarter and full year 2024 performance. Our fourth quarter and full year 2024 results were released this afternoon and are available on the SEC's EDGAR system and on our website, www.vandapharma.com. In addition, we are providing live and archived versions of this conference call on our website. Joining me on today's call is Dr. Mihael Polymeropoulos, our President, Chief Executive Officer, and Chairman of the Board, and Tim Williams, our General Counsel. Following my introductory remarks, Mihael will update you on our ongoing activities. I will then comment on our financial results before we open the lines for your questions. Before we proceed, I would like to remind everyone that various statements that we make on this call will be forward-looking statements within the meaning of federal securities laws.

Our forward-looking statements are based upon current expectations and assumptions that involve risks, changes in circumstances, and uncertainties. These risks are described in the cautionary note regarding forward-looking statements, risk factors, and management's discussion and analysis of financial condition and results of operations sections of our most recent annual report on Form 10-K, as updated by our subsequent quarterly reports on Form 10-Q, current reports on Form 8-K, and other filings with the SEC, which are available on the SEC's EDGAR system and on our website. We encourage all investors to read these reports and our other filings. The information we provide on this call is provided only as of today, and we undertake no obligation to update or revise publicly any forward-looking statements we may make on this call on account of new information, future events, or otherwise, except as required by law.

With that said, I would now like to turn the call over to our CEO, Dr. Mihael Polymeropoulos.

Mihael Polymeropoulos (CEO)

Thank you very much, Kevin, and good afternoon, everyone. Thank you for joining us to discuss Vanda's fourth quarter and full year 2024 results. As we discussed in our press release earlier this afternoon, strong revenue growth for Fanapt is putting us on a significant growth trajectory for 2025 and beyond, supported also by the commercial performance of HETLIOZ and PONVORY. The Fanapt long-acting injectable program, the new drug application for Bysanti mid-cyperidone for bipolar disorder and schizophrenia, along with its development for major depressive disorder, have the potential to drive future growth in our psychiatry portfolio for many years to come. Tradipitant's new drug application for motion sickness was filed with a potential approval this year while we're pursuing approval in gastroparesis and the development of Tradipitant to improve tolerability of GLP-1 analog Wegovy.

Our anti-inflammatory portfolio anchored by PONVORY was strengthened with the addition of Imsidolimab from AnaptysBio, an IL-36 receptor antagonist for the treatment of generalized pustular psoriasis. We plan to file a BLA later this year while we're exploring registration in Europe and Japan, as well as the development of this novel drug for other inflammatory disorders with an unopposed action of the IL-36 system. In 2024, we returned to revenue growth driven by the commercial launches in bipolar disorder and multiple sclerosis and advanced our development pipeline with a number of products at or near marketing applications. All this was achieved by the hard work, ingenuity, and efficiency of our organization and its wonderful people. I will now turn to Fanapt. Fanapt was approved in the second quarter of 2024 for the acute treatment of bipolar I disorder.

Vanda initiated the commercial launch of Fanapt in this indication in the third quarter of 2024. In the fourth quarter, as compared to the fourth quarter of 2023, new patient starts as reflected by new-to-brand prescriptions, or NBRX, increased by over 160%, and Fanapt net product sales increased by 18%. A dedicated specialty sales force of approximately 200 persons has been promoting Fanapt, supported by a speaker program to improve peer-to-peer awareness. Given the successful trajectory and consistent with other peers, we're currently in the process of further expanding our sales force to 300 representatives, which will allow for increase in both reach and frequency. In January of 2025, we began our direct-to-consumer advertising to increase general consumer awareness of Fanapt. We expect product adoption to continue as more prescribers develop treatment experiences and identify candidate patients.

Vanda also initiated a phase three program for the long-acting injectable LAI formulation of Fanapt in the fourth quarter of 2024. The long-acting injectable, once-a-month Fanapt, is evaluated in relapse prevention for schizophrenia, where the oral formulation has already been shown to be successful and is already included in the Fanapt prescribing information. While all products so far have been developed in double-blind placebo-controlled studies, and while Vanda and FDA have agreed on this design, an IRB, Institutional Review Board, has objected to a placebo-controlled design for schizophrenia maintenance. We're evaluating with the FDA ways to proceed outside of a placebo-controlled study, which could include a bridging study with the oral formulation. This evaluation is not specific to Vanda, and the outcome of this design will likely be required of others.

Vanda plans to initiate a study for the Fanapt long-acting injectable as a once-a-month injectable for the treatment of hypertension to address both treatment resistance and treatment compliance. In the course of our extensive clinical program with Fanapt for over 20 years, we have now identified an unexpected but robust benefit in treating hypertension with Fanapt. Specifically, in a large meta-analysis of placebo-controlled studies, we have identified a rapid and sustainable effect in reducing systolic and diastolic blood pressure, especially among people with baseline hypertension. The effect size is comparable to effective Antihypertensives. While the exact mechanism is not known, we believe that this effect is likely due to the mixed alpha serotonin and dopamine receptor antagonism observed with Fanapt. We plan to initiate a study to evaluate this effect with the once-a-month injectable Fanapt LAI in people with treatment-resistant hypertension.

It has been reported that medication non-adherence in hypertension is a significant public health risk, and as such, if we are successful in our studies, Fanapt LAI could become the first medication to address this large public health need. Additionally, Vanda submitted a marketing authorization application in Europe in the fourth quarter of 2024 for Fanapt, and that is a European Medicines Agency for bipolar I disorder and schizophrenia. I will now turn to Bysanti, known as mid-cyperidone. Vanda expects to submit a new drug application for Bysanti for the treatments of acute bipolar I disorder and schizophrenia to the U.S. Food and Drug Administration in the first quarter of 2025. Exclusivity, including pending patent applications, could extend into the 2040s. Bysanti is an active metabolite of allopurinol and has been extensively studied.

In the last year, we have met with the FDA and agreed upon the clinical and manufacturing requirements, and we're now prepared to submit a new drug application in the coming weeks. Vanda initiated a phase lll clinical study for Bysanti as a once-a-day adjunctive treatment for major depressive disorder in the fourth quarter of 2024. Results are expected in 2 026. I will now move on to HETLIOZ, as MElkin. Vanda has initiated clinical programs in pediatric insomnia and delayed sleep phase disorder, and these programs are ongoing. Vanda's MAA for HETLIOZ and HETLIOZ LQ for Smith-Magenis syndrome is now pending with the European Medicines Agency. In addition, Vanda is continuing to pursue the approval of HETLIOZ in sleep-onset insomnia and the treatment of jet lag. Vanda has completed successfully multiple studies in these indications that have demonstrated substantial evidence of efficacy and a positive benefit-risk profile.

Vanda has requested an FDA hearing on the insomnia indication, and an appeals court is expected to rule in the coming months on the jet lag application. PONVORY, on acimode. Vanda initiated the commercial launch of PONVORY for the treatment of relapsing forms of multiple sclerosis in the third quarter of 2024. A new specialty sales force is now promoting PONVORY for this indication across the United States. We believe that PONVORY's profile, when appreciated, will drive the preferences of prescribers and patients. The sales force is supported by a new speakers program for peer-to-peer awareness. Investigational new drug applications for PONVORY in the treatments of psoriasis and ulcerative colitis were accepted by the FDA in the fourth quarter of 2024. PONVORY has been previously shown to be effective in treating acute episodes of psoriasis as well as preventing relapse.

This study was conducted by Actelion before Vanda's acquisition of the product, and the results have been published. Vanda is now finalizing the development program that could lead to a new drug application filing in this indication. Tradipitant. The new drug application for Tradipitant for the treatment of motion sickness was submitted to the FDA in the fourth quarter of 2024. This application is supported by three positive studies in prevention of motion-induced vomiting in actual sea travel conditions. We expect an FDA decision later this year. Vanda has recently initiated a clinical trial to study Tradipitant in the prevention of vomiting induced by a GLP-1 analog, Wegovy, that is semaglutide, in the fourth quarter of 2024. A frequent and at times severe treatment-emerging adverse event with GLP-1 analogs is nausea and vomiting, which requires slower titration and delayed onset of effect.

We're evaluating whether Tradipitant can prevent Wegovy-induced nausea and vomiting, and if it does, it could become a very useful product during GLP-1 analog treatment initiation. Vanda has now accepted the opportunity for a hearing with the FDA on the approval ability of the NDA for Tradipitant for the treatment of symptoms of gastroparesis. Vanda has identified a number of faults in the FDA review that led to a complete response letter, and we believe that if allowed to be reviewed by experts, they would also reach the conclusion that Tradipitant can be a useful product in treating symptoms of gastroparesis. In the meantime, more than 50 patients are currently treated with Tradipitant through the expanded access program, and many additional ones are being evaluated to initiate treatment. Imsidolimab.

In February 2025, Vanda announced it entered into an exclusive global license agreement with AnaptysBio, Anaptys, for the development and commercialization of Imsidolimab, that is an IL-36 receptor antagonist monoclonal antibody. Vanda expects to initiate and complete the technology transfer activities in 2025 and to immediately begin preparing the Biologic License Application BLA and MAA for generalized pustular psoriasis GPP for the U.S. and European Union. Generalized pustular psoriasis or GPP is a rare, severe skin disorder that is often caused by recessive mutations in the IL-36 RN gene, a regulator of the IL-36 activity. The role of such mutations in heterozygous state, which are far more common, is not yet appreciated, but it may play a significant role in the pathogenesis and progression of other inflammatory skin conditions.

We plan to file a BLA later this year while we're exploring registration in Europe and Japan, as well as the development of this novel drug in other inflammatory disorders with an unopposed action of the IL-36 cytokine system. Finally, on early-stage program highlights, VQW765, an alpha-7 nicotinic acetylcholine receptor partial agonist, is currently in clinical development for the treatment of acute performance anxiety in social situations. We have previously reported results from a phase ll study with encouraging outcomes in a model of acute performance anxiety. We plan to meet with the FDA in the coming months at the end of phase two meeting and plan to initiate phase lll program in social anxiety disorder in 2025.

The IND application for VCA894A, an antisense oligonucleotide in the treatment of sarcotubular myopathy axonal type 2S, and inherited peripheral neuropathy for which there is no available treatment, was accepted by the FDA in 2024. The phase I clinical study for VCA894A is expected to enroll this single patient by mid-2025. In December 2024, Vanda announced that the FDA has granted orphan drug designation for VGT1849A, a selective antisense oligonucleotide-based JAK2 inhibitor for the treatment of polycythemia vera, a form of a rare hematologic malignancy that is estimated to affect 1 in 2,000 Americans.

I will just review the key regulatory milestones: Tradipitant NDA for motion sickness submitted in Q4 2024, Fanapt MAA in Europe for bipolar I disorder and schizophrenia submitted in Q4 2024, HETLIOZ MAA in Europe for Smith-Magenis syndrome submitted in Q4 2024, Bysanti new drug application for bipolar I disorder and schizophrenia expected to be submitted in Q1 2025, and Imsidolimab BLA in generalized pustular psoriasis expected to be submitted in 2025. With that, I'll turn now to Kevin to discuss our financial results. Kevin.

Kevin Moran (CFO)

Thank you, Mihael. I'll first discuss the results for the full year 2024 before turning to the fourth quarter of 2024. Total revenues for the full year 2024 were $198.8 million, a 3% increase compared to $192.6 million for the full year of 2023.

As Miles mentioned, this increase was primarily due to increased Fanapt revenue as a result of the bipolar commercial launch and the introduction of PONVORY revenue following our acquisition of the product in December of 2023, partially offset by decreased HETLIOZ revenue as a result of generic competition. Let me now break this down by product. Fanapt net product sales were $94.3 million for the full year 2024, a 4% increase compared to $90.9 million for the full year 2023. The increase in net product sales relative to the full year 2023 was attributable to increased volume and increased price net of deductions. HETLIOZ net product sales were $76.7 million for the full year 2024, a 23% decrease compared to $100.2 million for the full year 2023. The decrease relative to the full year 2023 was the result of continued generic competition in the U.S.

HETLIOZ net product sales as reported for the first quarter of 2023 reflected higher unit sales as compared to recent prior periods. The higher unit sales during the first quarter of 2023 resulted in a significant increase of inventory stocking at specialty pharmacy customers at March 31, 2023. During the remainder of 2023, although there was continued destocking at specialty pharmacy customers, inventory levels remained elevated relative to inventory levels prior to the entrance of generic competition and continue to remain elevated throughout 2024. Going forward, HETLIOZ net product sales may reflect lower unit sales as a result of reduction of the elevated inventory levels at specialty pharmacy customers or may be variable depending on when specialty pharmacy customers need to purchase again. Further, HETLIOZ net product sales will likely decline in future periods, potentially significantly related to continued generic competition in the U.S.

Additionally, the company constrained HETLIOZ net product sales for the years ended December 31st, 2024 and 2023 to an amount not probable of significant revenue reversal. As a result, HETLIOZ net product sales could experience variability in future periods as the remaining uncertainties associated with variable consideration related to inventory stocking by specialty pharmacy customers are resolved. PONVORY net product sales were $27.8 million for the full year 2024 and include approximately $3 million of variable consideration that may be subject to dispute, but that the company believes is not probable of significant revenue reversal. As a reminder, we completed the acquisition of the U.S. and Canadian rights to PONVORY in December of 2023. As such, this represents the fourth full quarter of PONVORY revenue recognition at Vanda and significant progress in diversifying our product mix with innovative and value-generating products.

For the full year 2024, Vanda recorded a net loss of $18.9 million compared to net income of $2.5 million for the full year 2023. The net loss for the full year 2024 included an income tax benefit of $4 million as compared to an income tax provision of $3.8 million for the full year 2024. Of note, on the tax side, the company assesses the need for valuation allowance against its deferred tax asset each quarter through the review of all available positive and negative evidence. The company generated a pre-tax loss for the year ended December 31, 2024. If the company continues to generate pre-tax losses and/or if the company's projections indicate pre-tax losses in future periods, the conclusion about the appropriateness of the valuation allowance could change in a future period.

An increase in the valuation allowance would result in a non-cash income tax expense during the period of change. Operating expenses for the full year 2024 were $239.4 million compared to $206.6 million for the full year 2023. The $32.8 million increase was primarily driven by higher SG&A expenses related to spending on Vanda's commercial products as a result of the commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis and legal and other corporate activities, as well as higher intangible asset amortization expense due to the amortization recorded on the PONVORY intangible asset. During 2024, we commenced a host of activities as part of our commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis, including an expansion of our salesforce and the development of prescriber awareness and comprehensive marketing programs.

SG&A expenses may increase in future periods as a result of the continued ongoing commercial efforts around Fanapt in bipolar I disorder and PONVORY in multiple sclerosis. Vanda's cash, cash equivalents of marketable securities referred to as cash, as of December 31st, 2024, was $374.6 million, representing a decrease of $1.6 million compared to September 30, 2024, and a decrease of $13.6 million compared to December 31st, 2023. Turning now to our quarterly results. Total revenues for the fourth quarter of 2024 were $53.2 million, a 17% increase compared to $45.3 million for the fourth quarter of 2023, and a 12% increase compared to $47.7 million in the third quarter of 2024. The increase as compared to the fourth quarter of 2023 was primarily due to the introduction of PONVORY revenue following our acquisition of the product in December of 2023 and increased Fanapt revenue.

Fanapt net product sales were $26.6 million for the fourth quarter of 2024, an 18% increase compared to $22.6 million in the fourth quarter of 2023. The increase in Fanapt revenue between the fourth quarter of 2024 and the fourth quarter of 2023 was primarily attributable to an increase in volume, which was driven by increased prescription demand or TRXs, as reported by IQVIA Exponent, and inventory stocking at the wholesalers. Historically, Fanapt inventory at wholesalers has ranged between three and four weeks on hand as calculated based off trailing demand. As of the end of the fourth quarter of 2024, Fanapt inventory at wholesalers was just above four weeks on hand.

Fanapt prescriptions in the fourth quarter of 2024 increased by approximately 9% compared to the fourth quarter of 2023, and Fanapt new patient starts in the fourth quarter of 2024, as reflected by new-to-brand prescriptions or NBRX, increased by over 160% compared to the fourth quarter of 2023. Fanapt net product sales in the fourth quarter of 2024 increased by 11% as compared to $23.9 million in the third quarter of 2024. Fanapt prescriptions in the fourth quarter of 2024 increased by approximately 7% compared to the third quarter of 2024. Turning now to HETLIOZ. HETLIOZ net product sales were $20 million for the fourth quarter of 2024, a 5% decrease compared to $21.1 million in the fourth quarter of 2023.

The decrease in net product sales relative to the fourth quarter of 2023 was attributable to a decrease in price net of deductions, partially offset by an increase in volume. HETLIOZ net product sales in the fourth quarter increased by 12% as compared to $17.9 million in the third quarter of 2024. Finally, turning to PONVORY. PONVORY net product sales were $6.5 million in the fourth quarter of 2024, an increase of 11% compared to $5.9 million in the third quarter of 2024. The increase in net product sales was attributable to an increase in volume of units sold, partially offset by a decrease in price net of deductions. The increase in volume in the fourth quarter of 2024 was partially attributable to a temporary inventory destocking in the third quarter at the specialty distributors and pharmacies due to the transition of distribution from Janssen to Vanda.

As a reminder, we completed the acquisition of the U.S. and Canadian rights to PONVORY in December of 2023. For the fourth quarter of 2024, Vanda recorded a net loss of $4.9 million compared to a net loss of $2.4 million for the fourth quarter of 2023. The net loss for the fourth quarter of 2024 included an income tax benefit of $1.6 million as compared to an income tax provision of $0.7 million for the fourth quarter of 2023. Operating expenses in the fourth quarter of 2024 were $63.5 million compared to $52.4 million in the fourth quarter of 2023.

The $11.1 million increase was primarily driven by higher SG&A expenses related to spending on Vanda's commercial products as a result of the commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis and legal and other corporate activities, partially offset by a decrease in R&D expense primarily driven by lower spend on our Tradipitant development programs. Operating expenses in the fourth quarter of 2024 increased by $4.8 million as compared to $58.7 million in the third quarter of 2024. This increase was primarily driven by higher R&D spend due in large part to increased expenses on our psychiatry programs and increased spending on Vanda's commercial products as a result of the commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis.

During 2024, we commenced a host of activities as a result of the commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis, including an expansion of our salesforce and the development of prescriber awareness and comprehensive marketing programs. SG&A expenses may increase in future periods as a result of the continued ongoing commercial efforts around Fanapt in bipolar I disorder and PONVORY in multiple sclerosis. With regards to the launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis, as I mentioned, the launches were initiated in 2024, and we expect to continue to build out our full commercial infrastructure with the impact of these commercial efforts expected to contribute to revenue growth in 2025 and beyond. We have already seen significant progress in our commercial activities.

Several lead indicators suggest a strong initial market response to our commercial launch of Fanapt in bipolar I disorder, including new patient starts as reflected by NBRX increasing by over 160% in the fourth quarter of 2024 as compared to the fourth quarter of 2023. Our Fanapt salesforce continues to expand. Currently, our salesforce has grown to over 200 persons, and we have now initiated a further expansion, as Mihael has mentioned. In addition to our Fanapt salesforce, we have established a specialty salesforce to market PONVORY to neurology prescribers around the country.

The expansion has allowed us to significantly increase our reach and frequency with prescribers, and we've now had over 700 Fanapt prescriber awareness programs completed in 2024, and the PONVORY prescriber awareness program continues to expand with over four times as many programs completed in the fourth quarter of 2024 as compared to the third quarter of 2024. Before turning to our financial guidance, I would like to remind folks that with Fanapt , HETLIOZ, and PONVORY already commercially available, the Tradipitant NDA for motion sickness submitted to the FDA, the Bysanti NDA for bipolar I disorder and schizophrenia expected to be submitted in the coming weeks, and a BLA for Imsidolimab expected to be submitted later this year, Vanda could have six products commercially available in 2026.

Turning now to our financial guidance, Vanda expects to achieve the following financial objectives in 2025: total revenues from Fanapt, HETLIOZ, and PONVORY of between $210 million and $250 million. This revenue range would imply revenue growth in 2025 of between 6% and 26% as compared to full year 2024 revenue. It is worth commenting that the quarterization of revenue in 2025 will be impacted by several items, including the Medicare benefit redesign portion of the Inflation Reduction Act, which went into effect as of January 1st, 2025. The implementation of the benefit redesign is expected to negatively impact gross to net for the Medicare payer segment of our products, more significantly on Fanapt and HETLIOZ. Note that this change is not linked specifically to Vanda but is an industry-wide change, which will have varying impacts on pharmaceutical companies.

Insurance plan transitions: as patients adjust to new insurance plans to start the year, there may be some disruption in the first quarter. This is also a typical industry-wide occurrence. As I previously mentioned, Fanapt inventory levels as of December 31st, 2024, were higher than typical levels based on trailing demand. If wholesalers adjust their inventory to historical levels, this could have a short-term negative impact on revenue in the period in which the destocking occurs. Given the conditional investments that Vanda is currently making to facilitate future revenue growth, both in the form of R&D investments and potentially outsized commercial investments, which could increase depending on the success of these commercial strategies, Vanda is not providing 2025 cash guidance at this time. Vanda will continue to evaluate its ability to provide cash guidance in future periods.

It is worth noting that the quarterization of cash balances will be impacted by several items, including payments totaling $15 million, which were made to AnaptysBio in the first quarter of 2025 upon entering into the global license agreement for Imsidolimab. Fees and costs associated with the filing of our applications with regulatory agencies in the U.S. and Europe, including the Bysanti NDA for bipolar I disorder and schizophrenia, and the standard timing of certain items paid in the first quarter each year. Given the significant progress made during 2024 on establishing our commercial infrastructure and the commercial investments we expect to make in coming periods, Vanda is providing 2030 revenue targets.

For the psychiatry portfolio alone, Vanda is targeting annual revenue in excess of $750 million in 2030, assuming the potential approval of Bysanti for the treatments of acute bipolar I disorder and schizophrenia in early 2026, the potential approval of Bysanti for the treatment of MDD, and the potential approval of Fanapt LAI. Vanda is also targeting total annual revenue in excess of $1 billion in 2030. It is worth noting that the revenue economics for Bysanti are expected to be significantly favorable relative to the current revenue economics for Fanapt. The potential market opportunity for our growing psychiatry portfolio is significant and necessitates the increased investments we are currently making to enhance the commercial profile of Fanapt, bring Bysanti and Fanapt LAI to market, and expand the Bysanti label to include major depressive disorder. With that, I'll now turn the call back to Mihael.

Mihael Polymeropoulos (CEO)

Thank you, Kevin. At this time, we'd like to answer any questions you may have.

Operator (participant)

Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press Star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press Star 1 again. Our first question comes from the line of Charles Duncan from Cantor Fitzgerald. Please go ahead.

Charles Duncan (Managing Director)

Hey, good afternoon, Mihael and team. Congrats on a good year, seeing the commercial turn as well as a ton of things going on with the pipeline, so lots of productivity. I had a question first on commercial and then pipeline. With regard to Fanapt, I guess I'm wondering, as you see that Q-on-Q growth, where do you think you're picking up traction and what types of prescribers? I wanted to ask you about that 300 reps, the 50% growth in the salesforce. I'm wondering if you think that'll be sufficient to, I guess, compete with potentially larger pharma companies coming in in marketing, obviously COVENFY, but also perhaps J&J in the future with CAPLYTA.

Mihael Polymeropoulos (CEO)

Yeah, thank you very much, Charles. In terms of where the growth is coming from, the prescribers that are coming to Fanapt are prescribers that have patients with bipolar disorder, and this is a difference from the smaller group of psychiatrists and psychiatric nurses that serve schizophrenia patients. It seems that the growth is exclusively coming outside of schizophrenia. In terms of the size of the salesforce, as you know very well, this is a highly promotionally sensitive class of drugs, and we have very recent examples of successful commercialization from some of our peers. Whether this is the right-sized salesforce, I would venture to say likely it's going to be on the lower side, but certainly you want to build rapidly, but at the same time, do not jeopardize the quality and very important training of this salesforce.

Now, we do see the potential competition by more deep-pocketed big pharma, of course, BMS with COVENFY. At this time, they will be primarily focused on the only indication that they have, schizophrenia, and that is not our main focus now. In terms of J&J, if they complete the acquisition of Intra-Cellular, certainly there's going to be a lot of strength, but it seems that the people there will be in patients with major depression if they succeed in securing the approval in that indication, which seems quite possible given the very nice data they have.

Charles Duncan (Managing Director)

Very good, Mihael. That's helpful. It makes sense. With regard to the DTC that you started in January, I assume that's targeting then the bipolar patients. Do you think that those patients are amenable to picking up the messaging of the DTC and perhaps bringing that to their prescribers and talking about Fanapt?

Mihael Polymeropoulos (CEO)

Yeah, thank you. Yes, the target is specifically for people with bipolar I disorder, and certainly we don't have to guess on the effectiveness in that before us, there have been others, almost every other drug recently in the category, they have advertised the DTC, which increased not just awareness but also confidence of support of the drug among patients. We are also finding it is actually intriguing to prescribers themselves. We believe that is a very effective way to increase awareness. I would point out that Vanda has a significant track record in efficiently launching a DTC campaign and buying media. I think that's going to become very important in the coming months.

I would like to underscore, Kevin suggested that at this time, we do not give a cost guidance, and this is primarily driven by trying to gauge what is the right-sized direct-to-consumer, and you buy as you go. We, unlike some large companies, are not doing pre-buys at this time. We buy on demand, and we are very carefully evaluating the return on our investment. It is a measured approach, but we are prepared to make a significant investment provided a good ROI on the other side.

Charles Duncan (Managing Director)

Thank you for that information. On Bysanti, if I could ask a quick question. I'm intrigued with the one per day MDD study that you started towards the end of last year. I'm wondering if you have specific information on either Fanapt or Bysanti that suggests that it may have activity in MDD as well as perhaps depressed patients with bipolar. What is the kind of rationale behind that phase three?

Mihael Polymeropoulos (CEO)

Yeah. Of course, you know that we have a lot of experience on Fanapt, iloperidone, with twice a day, but we also have experience in the utilization across different doses. Our studies have been primarily done on the higher dose side, 12 milligrams a day divided dose or 24 milligrams a day as a divided dose. Our observations so far suggest that a large number of patients have been prescribed monthly doses, which reflect a total in the day of approximately 12 milligrams on average. We know that based on the pharmacokinetics and steady-state levels, that once a day, 12 milligrams does not present any significant issues of peak to trough and tolerability. The combination of all this suggested to us that a once-a-day administration of Bysanti will be a good approach in major depressive disorder.

As you can guess, it happens also to be likely more convenient than a twice-a-day dosing.

Charles Duncan (Managing Director)

For sure. Look forward to that. Final question. Imsidolimab, congrats on the recent in-licensing. I'm intrigued with that program. BLA later on this year. I think Enaptis, and I'm not going to ask you to defend Enaptis, but I think they spoke about a BLA as early as October 20 in 2023 as having already been filed. I'm wondering if you have a sense of what the delay in filing is and if a pre-BLA has been conducted, or is that all the kind of stuff that you'll do once you fully accept all the information from them?

Mihael Polymeropoulos (CEO)

Yeah. I cannot comment on the first part of the question, but a pre-BLA meeting with the FDA on the GPP indication has been conducted, and upon review of this information, we're confident that we have in hand what needs to be had for filing. Of course, we're only a few days away, but I would say AnaptysBio is a great partner on this. Transition is ongoing quickly of materials, so we're confident we'll be able to file this BLA within this year. I have to say, Charles, that maybe we get an opportunity at a future call. We're intrigued by the mechanism of action, and we believe that the IL-36 cytokine system is a perhaps not fully explored therapeutic in a number of autoimmune inflammatory conditions. Of course, we understand the role in keratinocytes and generalized pustular psoriasis.

As I pointed out in my discussion, GPP is caused by two beds in a recessive disorder. Of course, there is a much larger portion of the population that they're heterozygous carriers of an IL mutation, which under some circumstances, it may lead to a relatively unopposed action of IL-36. There are theories of what this population may be. There may be a class of people with atopic dermatitis or psoriasis or actually other inflammatory conditions where IL-36 is important in monitoring intruders at barrier tissues. More to be discussed in the future.

Charles Duncan (Managing Director)

Good pipeline. Lots going on. Thanks for taking the questions. Congrats on the progress.

Mihael Polymeropoulos (CEO)

Thanks, Charles.

Our next question comes from Raghuram Selvaraju from H.C. Wainwright. Please go ahead.

Raghuram Selvaraju (Managing Director)

Hi. Thanks very much for taking my questions and congrats on all the recent progress. First of all, I wanted to start with a question around your anticipated timing for the development of the IL-36 long-acting injectable. Specifically, I wanted to ask when you anticipate enrolling the first patient in that pivotal program and how long you expect enrollment to take, as well as if you can provide any kind of updated outlook on the competitive landscape given the fact that this appears to be changing quite rapidly, although it obviously is also reflective of a steadily expanding broader total addressable market. Thank you.

Mihael Polymeropoulos (CEO)

Yeah. Thank you very much for the question. At the bottom, I would say we agree with you that there appears to be a lot of need and large commercial opportunity around injectable antipsychotics, and especially new entrants of molecules that have not been translated from oral to a long-acting injectable like Fanapt. In terms of the program, we're ready to go. In fact, that program can be initiated imminently. The initial treatment period is about a 12-week period of stabilization before we lead to the re-randomization relapse prevention. What I mentioned, Ram, is that the question from the IRB was that they felt no one should be running placebo-controlled studies on a relapse prevention mode, and they offer that placebo people may be at some risk.

We disagree with that, but nonetheless, it is the IRB, and we are in total agreement with the FDA on what protocol is needed. In fact, we are in agreement that this study, if successful, which we expect it to be, is the pivotal study required for registration. We are actually waiting. We've launched this question to the FDA, and they're working, I guess, on their policy side to see what this shift in the IRB means and what type of study may be required. Be it as it may, the placebo is the most involved study, and we could end up with a more simple design where there is a bridging of sorts with the oral formulation. No matter what it is, we can start the study very quickly.

Now, in terms of timing to enrollment, as you know, that's hard to evaluate given the difficulty recruiting in general. This study is a long study. Recruitment in large could take up to one year. That means, I think we've discussed before, that we will not expect results, but in sometime in 2027.

Raghuram Selvaraju (Managing Director)

Okay. With respect to the guidance that you provided today on potential revenue in 2025, can you confirm that even the upper end of that guidance range does not actually include projected contribution from Tradipitant in any indication or Imsidolimab? Is that correct?

Mihael Polymeropoulos (CEO)

That is correct. The range guidance we're giving is solely based on the commercialized products today in the commercialized indications. Of course, we could be pleasantly surprised towards the upper end depending on the Fanapt trajectory and PONVORY gaining speed. On HETLIOZ, given the generic contribution, we have more tamed expectations.

Raghuram Selvaraju (Managing Director)

To what extent do you anticipate there to be a significantly larger number of generic purveyors of Tasimelteon by the end of 2025 versus the end of 2024?

Mihael Polymeropoulos (CEO)

At this time, we do not expect that field to change outside of the three approved ones.

Raghuram Selvaraju (Managing Director)

Okay. The last question is with respect to broader reimbursement changes. Any specific developments of note that you anticipate taking effect in 2025 that could significantly impact gross to nets?

Kevin Moran (CFO)

Yep. Hey, Ram. It's Kevin. The main one, which we talked about in the scripted portion a bit, is the introduction of the Medicare benefit redesign, which went into effect at the beginning of January. The reminder there is previously where there was the donut hole concept and the manufacturer had a portion of that contribution until the patient had moved through the donut hole for the year. The benefit redesign has a different structure where for the catastrophic portion of the coverage, the manufacturer has either 10% or 20% contribution to that, with some exceptions for different types of manufacturers and different types of patient populations. That went into effect at the beginning of January, as I mentioned, and was factored into our projections for 2025.

Raghuram Selvaraju (Managing Director)

Okay. Thank you.

Kevin Moran (CFO)

Thanks, Ram.

Mihael Polymeropoulos (CEO)

Our next question comes from the line of Andrew Tsai from Jefferies. Please go ahead.

Andrew Tsai (Senior VP)

Hey. Thanks. Good afternoon. Appreciate all the updates. First question is about the 2030 guidance. What exactly compelled you guys to provide that guidance today? Within that $1 billion guidance, of course, 750 is coming from psychiatry. How much of that 750 is based on products or indications that have yet to be approved as opposed to currently approved products? Thanks.

Kevin Moran (CFO)

Thanks, Andrew. Yeah. Maybe starting with the psychiatry portfolio first. Obviously, with Fanapt currently on the market, doing about $100 million this year. With the commercial investments we're making, hoping to see growth as we obviously head into next year and beyond. Even beyond that, we noted that included in that 2030 projection is the approval of Bysanti for bipolar I disorder and schizophrenia, hopefully next year, and then potentially a label expansion there in MDD beyond that, as well as the approval of Fanapt in LAI. The one thing I also made note of in the script that's an important piece to that is that Bysanti is expected to have very different economics than Fanapt currently has.

At a minimum, that's due to the price reset that we would experience under Medicaid with a new drug application being approved. All of those, obviously, we didn't provide kind of a breakout of the contributions of those individual factors, but hopefully that gives you a sense of what contributions would go into the $750 million from existing product indications, future product indications. On the balance, obviously, with HETLIOZ and PONVORY on the market, HETLIOZ, as Mihael has mentioned, where our expectations are a bit more tamed, at least on the short-term, and with PONVORY growing and hopefully even more so in the years to come. Also the possibility that we mentioned of an additional three products being on the market next year, including iloperidone, but also Tradipitant and imsidolimab. Those products also provide some of the bridge between the $750 million and the billion.

Andrew Tsai (Senior VP)

Thanks. When we think` about your overall business, where or when should we think the trough year is in terms of revenue and your total cash balance? Said another way, do you think the trough year already happened, or could it be somewhere in 2025 or a little bit later?

Kevin Moran (CFO)

Yeah. No, no. Thanks for the question there, Andrew. Obviously, with our reported revenue for this year being growth from the year before, we saw growth from about $193 million up to about $199 million in the most recent year, and our midpoint of our guidance being $230 million, which would imply about a 15% growth on 2024, I would say the trough year, as you kind of expressed it, is over the shoulder. Our expectation is that we're growing revenue from here, both with the existing products and indications, but obviously all the products and indications that we're planning on bringing to the market in the short-term and the long-term.

Andrew Tsai (Senior VP)

Okay. Thanks. Last question is for HETLIOZ. If we stripped out the indications where you're facing generics, how much sales are you generating from the other formulations or indications where HETLIOZ is not facing genericization? I guess the liquid formulation and the EU component, how much are those sales currently? Thank you.

Kevin Moran (CFO)

Yeah. Andrew, we haven't gotten into a breakout by geography or by indication, so I can't provide any further kind of color to that.

Andrew Tsai (Senior VP)

Very good. Thank you.

Kevin Moran (CFO)

Thanks, Andrew.

Mihael Polymeropoulos (CEO)

There are no further questions at this time. I'll turn the call back over to the team.

Oh, thank you very much for joining us on this call. We'll see you on a future earnings call. Thank you.

This concludes today's call. Thank you for joining. You may now disconnect.