Good morning, everyone. My name is Lucy Lai, a Research Associate at H.C. Wainwright. It's a great pleasure to welcome you all to H.C. Wainwright's 27th Annual Global Investment Conference. Thank you for taking the time to join us today. We hope you'll find these sessions insightful and engaging. Now, I'm delighted to introduce our next speaker, Mr. Kevin Moran, Senior Vice President and Chief Financial Officer of Vanda Pharmaceuticals Inc., a commercial-stage specialty pharmaceutical company focused on neurology, autoimmune diseases, and sleep disorders. Kevin, please.
Thank you very much, Lucy, and thanks to the entire H.C. Wainwright team for having us here. Excited to talk to you guys about our recent progress and future plans. Vanda Pharmaceuticals Inc. is a leading global biopharmaceutical company dedicated to innovating in the service of people's pursuit of happiness. We have three commercialized products. Our first product, Fanapt, was approved back in 2009 for schizophrenia. It was approved in 2024 for bipolar disorder, and we've been putting significant commercial efforts into the Fanapt franchise with that recent approval. Our second product is HETLIOZ. HETLIOZ was approved in 2014 in the U.S. for non-24-hour sleep-wake disorder, which we refer to as non-24. It was also approved in Europe for non-24-hour sleep-wake disorder in 2016 and is currently marketed in Germany.
Additionally, the capsule formulation and a new liquid LQ formulation were approved in 2020 for nighttime sleep disturbances in Smith-Magenis syndrome, or SMS. Our third commercial product, PONVORY, was acquired from Johnson & Johnson at the end of 2023 for $100 million, approved in multiple sclerosis, and we commercialize here in the U.S. with a separate organization commercializing in Europe. In addition to those three commercialized products, we have a very robust pipeline with a number of recent and upcoming regulatory submissions, as well as multiple products in development at various stages of development across a wide range of therapeutic areas. On the recent and upcoming regulatory milestone front, we have three upcoming PDUFA dates, the first of which is tradipitant for motion sickness, which has a PDUFA date of December 30th of this year.
The second one is Bysanti, which has a PDUFA date in February of 2026 for both schizophrenia and bipolar disorder. The final one is imsidolimab, which we in-licensed from AnaptysBio earlier this year, and we plan to submit a BLA by the end of this year, which will likely give us a PDUFA date sometime in the back half of next year. If successful on those three regulatory submissions, we could end 2026 with six commercial products relative to our current three commercial products. In addition to those commercialized products and our very robust pipeline, we currently have a very strong financial position with approximately $325 million in cash as of the end of the second quarter, with no debt. Now, in a bit more detail on our commercialized products. As I mentioned, Fanapt is approved in the U.S. for schizophrenia and bipolar disorder.
The 2024 approval of bipolar disorder resulted in us significantly expanding our commercial efforts here in the U.S. over the last year. That began with a significant increase in our commercial footprint, adding to about 150 sales representatives in the U.S. by the end of 2024, as well as the initiation of a number of marketing, direct-to-consumer, and other prescriber awareness efforts. As we tracked script growth through the end of last year, we saw nice script growth as we headed toward the exit of 2024, and then a relatively consistent Q1 compared to Q4, which is not unexpected given some of the seasonality you see around year-end insurance disruptions and the like. We saw very strong prescription growth in April, where we crossed 2,000 weekly TRXs for the first time in many years.
For some context, we had seen the second quarter of last year when we'd initiated some of our commercial efforts after the bipolar approval in the 1,300 to 1,400 weekly TRX number. Significant improvement as we headed towards the end of the first quarter, beginning of the second quarter, gave us additional conviction to further expand the commercial efforts. We've since increased our commercial sales force to approximately 300 sales representatives in the U.S., detailing to psychiatrists and other psychiatric targets. As we look to our more recent TRX activity, for the most recently reported weeks in August, we saw approximately 2,300 TRXs, again relative to that 1,300 to 1,400 that we saw in the second quarter of last year.
From an NBRX perspective, a new-to-brand perspective, at this time last year, we were seeing about 40 NBRXs per week, and for the most recently reported week, we saw approximately 240, so about 6x growth over the course of a year. We are very encouraged by all the commercial progress that we're seeing there in terms of sales force expansion, increased call activity, engagement with prescribers in a number of different mediums, and that now translating into meaningful script growth. In addition to our commercial efforts around Fanapt and bipolar disorder, we have the upcoming PDUFA date for Bysanti. As a reminder, Bysanti, or milsaperidone, is the active metabolite of iloperidone, where we disclosed late last year that we had very strong bioequivalence data and that we had had a pre-NDA meeting with the FDA, and we believed we had a data package sufficient for submission.
We submitted our NDA package in the early part of 2025 and press released that it had been accepted for filing with a PDUFA date in February of 2026. As part of that disclosure, we noted that there were no review issues identified at that time, which is of significance given that historically in our reviews with the FDA, both for applications that are ultimately approved or ultimately not approved, there's commonly review issues identified. The fact that there were no review issues identified at the time was obviously an encouraging sign for us. We then published our bioequivalence data at ASCP in May, and we continue to move towards our PDUFA date in February. As a reminder, Fanapt likely has an exclusivity end date around the end of 2027.
With the Bysanti approval early next year and an introduction sometime later in 2026, there'd be about, you know, somewhere between four and six quarters of commercial overlap while Fanapt is in the market and Bysanti is in the market at the same time, and then Fanapt will likely exit the market or, you know, enter its LOE phase at the end of 2027. In addition to the commercial efforts, therefore, around Fanapt and ultimately Bysanti, we also have Bysanti currently in a phase 3 trial for MDD, where results are expected at the end of 2026. Hopefully, with positive results there, we can move to an sNDA filing quickly thereafter and look to add to that to the label. In addition, we have a phase 3 program ongoing for the Fanapt, the long-acting injectable, currently in schizophrenia.
On the HETLIOZ side, as I mentioned, HETLIOZ was approved back in 2014 for non-24-hour sleep-wake disorder here in the U.S., and then in 2020 for a second orphan indication, sorry, non-24-hour sleep-wake disorder in 2014, and then a second orphan indication in 2020, which was nighttime sleep disturbances in Smith-Magenis syndrome. At the end of 2022, we had an unfavorable court ruling in the Delaware District Court that allowed generics to enter the market. Now, coming up as we head towards the end of 2025, the HETLIOZ market is approximately three years in with generic competition. We've seen an erosion in our revenue there, but we've seen an incredibly resilient patient population and persistency on the product, where HETLIOZ still maintains the majority of the market share in the space.
In order for us to maintain that market share beyond patient loyalty and other avenues, we've had to be more competitive from a pricing perspective, which has led to a more significant decrease in revenue than you otherwise would expect. As we head towards the end of 2025, through the first half of the year, we had approximately $37 million of revenue through the first two quarters of HETLIOZ, and that compares to about $77 million for the full year of last year, just to give you a sense of what we're seeing from a resiliency and maintenance perspective. In addition to the U.S., as I mentioned, HETLIOZ is approved in Europe for non-24-hour sleep-wake disorder, and we continue to pursue approval for Smith-Magenis syndrome in that market as well. In the U.S.
here, we have a number of different indications that we're pursuing, where we have had regulatory submissions for HETLIOZ in both insomnia and jet lag. Finally, on PONVORY, as I mentioned, we acquired PONVORY at the end of 2023 and completed the transition from Johnson & Johnson in the third quarter of 2024. We're very early here in the commercial launch of PONVORY in the U.S. Of note, during our second quarter earnings call, we commented that in the second quarter, we saw increased patient demand, albeit very small, relative to the first quarter, which is very encouraging, suggesting hopefully a stabilization of the market and then resumption of growth in future periods. In addition to PONVORY being commercialized in multiple sclerosis, we are pursuing PONVORY in other potential indications, including psoriasis and ulcerative colitis. A bit more detail on our strategic focus.
We remain focused on increasing our revenue organically through our existing products, that being both the current approved three products, Fanapt, which we're targeting significant commercial efforts and growth there, as well as HETLIOZ and PONVORY, and then expanding potentially to our up to six commercial products by the end of 2026 with our three upcoming PDUFA dates. In addition to growing revenue through those organic opportunities, we also remain focused on growing it through potential business development opportunities. As I've mentioned, at the end of 2023, we completed the acquisition of PONVORY from Johnson & Johnson, and early in 2024, we completed the in-licensing of imsidolimab from AnaptysBio.
While we remain interested in pursuing business development opportunities up and down the development pipeline, I think with our significantly increased commercial presence in both the psychiatry and neurology space, potentially leveraging a commercial product in that space in our existing infrastructure could make sense. In addition to increasing revenue, we remain focused on advancing our pipeline, as I mentioned, our three upcoming PDUFA dates, but in addition to that, we have a number of clinical programs at all stages of development that will have milestones in the upcoming years. Finally, a consumer focus. We remain very committed to increasing access and affordability for patients wherever possible and engaging directly with consumers wherever it makes sense.
In a bit more detail on our commercial priorities and milestones, although I've touched on some of this, again, on the Fanapt side, we're focused on the commercial launch of Fanapt in bipolar while continuing to maintain and promote in the schizophrenia market. We're pursuing our FDA approval for Bysanti, again with our PDUFA date in February, and that would hopefully be for both bipolar disorder and schizophrenia. We're pursuing our phase 3 program for Bysanti in major depressive disorder with results expected by the end of 2026. On HETLIOZ, we're focused on retaining market share in the face of generic competition, potentially growing the U.S. market in Smith-Magenis syndrome, where there is not generic competition in the U.S., seeking approval for HETLIOZ for Smith-Magenis syndrome in the European market, and continuing to bring HETLIOZ to the market in the U.S. and potentially in Europe for other indications.
On PONVORY, we're focused on our commercial launch of the product in multiple sclerosis while potentially pursuing other indications. With our tradipitant and PDUFA date right in front of us at the end of the year, we're focused on preparing the market for commercialization of tradipitant in motion sickness while continuing to pursue FDA approval for tradipitant in gastroparesis. On the R&D front, here's an overview of our late-stage clinical development pipeline. This doesn't capture some of our earlier stage programs, but just to give you a sense of how many late-stage programs we have. As I mentioned, Fanapt, we have the long-acting injectable in schizophrenia and potentially that program going into hypertension as well. We have Bysanti, where we have our upcoming PDUFA date on bipolar and schizophrenia, as well as our phase 3 for MDD.
On HETLIOZ, we have jet lag and insomnia both at the regulatory stage with a number of other indications in late stage as well. On PONVORY, in addition to the multiple sclerosis currently approved indication, we are pursuing psoriasis and ulcerative colitis and expect those to be phase 3 programs. On tradipitant and our gastroparesis and motion sickness programs are at the regulatory stage. Finally, on imsidolimab, as I mentioned, when we completed the in-licensing transaction with AnaptysBio, they'd already produced great clinical results with two phase 3 programs, the GEMINI 1 and GEMINI 2 programs. That is moving towards a BLA by the end of the year with our PDUFA date hopefully expected in the back half of next year. In a bit more detail on Fanapt lifecycle, as I mentioned, Fanapt was approved for bipolar disorder in April of 2024, where we've been making significant commercial investments.
We've also submitted an MAA to the EMA at the end of last year, and we'll be hopeful to bring Fanapt to that market as well. On the long-acting injectable, our phase 3 program is ongoing, and while we haven't communicated an expectation on timing of results, what we have said is that the LAI could reach the U.S. market sometime after 2026, and there are pending patent applications that, if issued, could extend exclusivity into the 2040s. As I also touched on very briefly, we've initiated a study of the LAI as a once-a-month injectable for the treatment of uncontrolled hypertension. On HETLIOZ, we continue to pursue our clinical programs across a whole host of indications, where both jet lag and insomnia are at the regulatory stage.
We had a recent announcement around a court decision for the jet lag NDA, where we expect to see some news flow in the coming months as both the courts and the FDA digest that court decision. On the tradipitant side, on gastroparesis, we continue to pursue FDA approval for tradipitant in patients with gastroparesis. As a reminder, in September of 2024, we received a CRL from the FDA on tradipitant for gastroparesis. Our phase 3 study reported results in February of 2022. This was a 12-week study of approximately 200 patients with idiopathic or diabetic gastroparesis. That followed our positive phase 2 study, where we reported results in December of 2018. On motion sickness, our NDA PDUFA date is at the end of this year, and supporting that filing were three clinical trial results, two positive phase 3 trials, and a positive phase 2 trial.
In just a bit more detail on tradipitant for gastroparesis, as I mentioned, we completed two clinical studies of tradipitant for gastroparesis. Gastroparesis represents a very significant unmet medical need, with the last approved treatment option approved more than 40 years ago. There's also a very large potential market opportunity for tradipitant in gastroparesis, with approximately 6 million people in the U.S. estimated to be impacted by gastroparesis. Of those 6 million, it's estimated that 600,000 have already been diagnosed, and supporting the robust size of the market and the patient awareness is 300,000 prescriptions on a monthly basis for metoclopramide, the only approved product in the disorder. A little more detail on the symptoms and clinical expression of gastroparesis.
Both diabetic or idiopathic gastroparesis are characterized by chronic nausea, where the patients suffer with debilitating severe nausea, vomiting, which can lead to weight loss and hospitalization, delayed gastric emptying, and other GI symptoms, including fullness and abdominal pain. As I mentioned, our clinical program is supported by two studies and an expanded access program. The phase 2 study that reported results in 2018 was a four-week study of approximately 150 adult patients stratified across both diabetic and idiopathic gastroparesis, where tradipitant was shown to be effective in improving nausea and the overall symptoms in patients with gastroparesis. The efficacy that was established in the four-week double-blind phase was persistent in the open-label phase. Our phase 3 study, the 3301 study, was a 12-week study of approximately 200 adult patients, again stratified between diabetic or idiopathic gastroparesis.
While the study did not meet its primary endpoint, when accounting for confounders, there was strong evidence of drug effect across a number of symptoms. The open-label phase remains open now with over 300 patients already enrolled. The expanded access program, where we initiated a program for patients who were requesting access outside of the clinical studies, continues to receive requests from patients reaching out to gain access to tradipitant, and we've now had multiple patients take tradipitant for more than a year. On the pooled study results, as part of our phase 3 readout, we looked at a pooled study of the phase 2 and the phase 3 study results. The population of this pooled study included 342 patients and measured relevant clinical endpoints. Of note, both the phase 2 and the phase 3 studies were large multi-site, randomized, double-blind, placebo-controlled studies.
In the pooled study analysis, tradipitant was shown to be effective on the primary endpoint parameter of daily diary nausea. The conclusion there is that both studies demonstrate the efficacy of tradipitant in relieving symptoms of gastroparesis. Finally, I'll turn to just a brief summary on our financial results. Our 2025 financial guidance is total revenues of $210 million to $250 million, a midpoint of $230 million. This compares to just below $200 million of revenue for 2024, approximately 15% year-over-year growth. Year-end cash guidance is to end the year with between $280 million and $320 million of cash, a midpoint of $300 million. As a reminder, we began the year with approximately $375 million of cash, so this would represent about a $75 million burn for the year.
In the second quarter of 2025, we had approximately $53 million of revenue, split across $29 million of Fanapt product revenue, $16 million of HETLIOZ product revenue, and $7 million of PONVORY product revenue. For our year-to-date results through the second quarter of 2025, we had revenues of approximately $103 million with operating expenses of approximately $182 million for a net loss of approximately $57 million. As I mentioned, we ended the quarter with approximately $325 million in cash and no debt. I thank everybody for their time and interest, and we look forward to providing updates as we move forward here through the exciting milestones ahead. Thanks, everybody.
Thank you so much. It's very impressive.