We are seeking to change that with a pipeline designed to address brain health disorders and improve public health. Brain health is fundamental to well-being and function at each stage of life. Through pioneering science, we aim to advance programs and have the potential to improve the lives of individuals living with brain health disorders and their families. We're focused on modulating brain network function and disruptive circuits, an underlying factor in many brain health disorders, starting with compounds that selectively modulate GABA and NMDA receptor activity. Our expertise in neuroactive steroids includes hydroxycholesterol, allowing us to choose compounds for development based on a number of factors, including the potential to modulate these circuits.

ZURZUVAE is an important example of how we leverage our deep expertise and understanding of these receptor systems to discover a novel therapy. ZURZUVAE was made commercially available in mid-December 2023, giving us about 10 days in 2023 where women with PPD in need of treatment could access healthcare providers. We're excited that we're getting this new treatment option to women who desperately need it. Of course, our work has continued in 2024, and inspired by the stories from our teams in the field in just the first few weeks of launch. Women with PPD and their families now have a treatment option with the potential to make a profound difference in their lives. And the providers with whom we've spoken see ZURZUVAE as a potential catalyst to increase much needed screening, diagnosis, and treatment of PPD across the healthcare system.

It's early, but I do believe that ZURZUVAE is the key to unlock the blockbuster potential of PPD, enabling us to help many women suffering from postpartum depression. Importantly, there have been encouraging developments across the treatment landscape. We're starting to see PPD recognized as an urgent medical condition. There's more conversation and dialogue about addressing stigma and the treatment system is mobilized to better support patients. I want to thank advocates and providers who have prioritized addressing maternal mental health treatment disparities. Turning to the launch progress, ZURZUVAE generated $824,000 in collaboration revenue during the fourth quarter of 2023. As a reminder, our reported collaboration revenue is 50% of the net sales Biogen records for ZURZUVAE.

As we are very early in launch stages, we're not discussing specific revenue expectations or launch trajectory. However, what I can say today is that we're encouraged by the initial progress we're seeing. Our early initiatives aimed at establishing ZURZUVAE as the first line therapy for women with PPD, have begun to translate into strong tailwinds for the launch of ZURZUVAE. Just a few critical highlights. We're hearing that women with PPD are starting to step forward to advocate for ZURZUVAE as they discuss treatment options with their healthcare providers. Healthcare providers, including psychiatrists, OB-GYN, primary care, nurse practitioners, and physician assistants, are writing prescriptions for ZURZUVAE in the treatment of PPD. A specialty distribution network is in place designed to provide a positive experience for patients with convenient home delivery.

The ZURZUVAE For You Patient Assistance program is helping to support timely access for eligible patients. Of course, as I said, we're early in launch days, and there are aspects of launch we certainly need to optimize, but the initial response and uptake are highly encouraging. Chris, and Kimi will provide additional updates later in the call, and we look forward to sharing more detail on our progress in the coming quarters. While the launch remains our top priority, we're also excited by all that we have ahead of us in 2024, with multiple data readouts expected across our ongoing studies in Dalzanemdor, also known as SAGE-718, as well as SAGE-324. We believe in the potential of both molecules to help patients in need and to become significant drivers of long-term value creation as we aim to strengthen our leadership position in brain health.

Additionally, we're excited about the continued progress on our early-stage pipeline with SAGE 319 and SAGE 421. We remain confident in our ability to continue to execute across our pipeline as we head into a catalyst-rich 2024. With that, I'll turn the call over to Chris to provide additional context on the ongoing commercialization of ZURZUVAE. Chris?

Chris Benecchi: Thanks, Barry. As Barry mentioned, we've made tremendous progress in these early days of ZURZUVAE’s launch in PPD, and I'm excited to discuss our recent achievements and ongoing initiatives. At SAGE, we share in the urgency to treat PPD. In the US, an estimated one in eight women, or approximately 500,000 women, who have a live birth, experience. Symptoms of PPD each year. Data suggests about half of those receive a diagnosis of PPD and approximately half of those begin treatment. The increasing recognition of PPD as a serious medical condition is a major step forward. However, we still have a collective responsibility to ensure maternal mental health is supported and treated as a core aspect of women's overall health.

With the approval and launch of ZURZUVAE, we believe there is new hope for women with PPD. We also believe the focus on diagnosis, screening, and treating PPD, provides an opportunity to make a meaningful impact on mothers, children, and families. And now, I'm happy to share some color on what we believe is an encouraging start to the early launch. At the beginning of the year, Barry highlighted our objective in establishing ZURZUVAE as the first line therapy for women with PPD. We believe to do so will require delivering broad, equitable, and affordable access for women with PPD, enabling early positive HCP and patient experiences, partnering with communities to improve the focus on maternal mental health, and providing clear education on ZURZUVAE and PPD to all stakeholders.

With that in mind, we are encouraged by the demand we saw in the initial days of the launch. Let me share some metrics we believe are important and reflective of the progress we've seen. As a reminder, we announced commercial availability in mid-December, so the data I'm sharing reflects demand from around 10 days when women with PPD could access HCPs. As of the end of the fourth quarter, there were approximately 120 prescriptions written. With added launch capabilities and both SAGE and Biogen sales representatives active in the field, we continue to be encouraged by the increasing number of prescriptions in early 2024. I'd like to note that this is a metric we intend to show in the initial quarters. However, over time, we will likely move away from this metric and focus primarily on shipments and collaboration revenue.

In December, we were pleased to see prescriptions written by psychiatrists and importantly OB-GYNs, who prescribe in approximately equal numbers. We also saw a small number of prescriptions written from primary care physicians, and a number of HCPs wrote multiple prescriptions. All of these trends have continued into early 2024. Of the prescriptions written in December, over 70% were shipped in December and early January. Our goal over time is for most women who are prescribed ZURZUVAE to receive the medication as quickly as possible. We saw many scripts in December take longer to ship than we'd like, which can be anticipated in the initial days of launch and over a holiday period. We expect that as launch progresses, women with PPD will have access to ZURZUVAE more rapidly, particularly as factors such as payer formulary decisions are made, HCPs and patients become more experienced in using our FT network, and the specialty pharmacy process is further optimized.

Moving on, as Barry noted, our patient support program, ZURZUVAE For You, is activated and working well. In December, the commercial-insured patients using the ZURZUVAE savings card paid no copay expenses. We maintain our commitment to the goal of having ZURZUVAE be both broadly accessible and affordable for women with PPD. And importantly, on the coverage front, conversations are advancing across national, regional, and government payers, and in the early weeks of the launch, the vast majority of ship prescriptions are being covered by payers, even as coverage policies are being developed. We are so far not encountering significant payer headwinds, and to the contrary, we are seeing positive payer engagement. As we've said, we expect commercial coverage formulary decisions to continue to come on board in the first half of 2024, with Medicaid stretching into the second half for certain States, as that process typically takes more time.

The early demand for ZURZUVAE is reflective of the strong enthusiasm we're hearing from HCPs and women with PPD for this medication. Further, as we look at who is driving the prescribing, we believe that the strong engagement across specialties and providers, represent HCP appreciation for the need to treat PPD as an urgent medical condition, regardless of the practice setting. And notably, these prescriptions are coming from HCPs, many of whom have been reached either through personal promotion, or who have engaged with our website digital content, reinforcing the initial impact of our omnichannel efforts. We are still in the early weeks of launch, and we know we have more work to do to help women with PPD access treatment. With that said, we're encouraged by what we're seeing so far.

The launch has reaffirmed the unmet need and urgency for a new medication for women living with PPD, and we know we need to continue to execute to maintain this momentum. I look forward to sharing additional details on our, and Biogen's commercialization efforts, in the coming quarters. With that, I will turn it over to Laura for a more detailed discussion of our recent pipeline progress and current clinical expectations. Laura?

Laura Gault: Thanks Chris, and good morning, everyone. Over 2023, we have made important progress on our pipeline programs, and I'm pleased to share our recent progress and plans for continued development over the coming quarters. I want to share my excitement to be part of such a significant moment for maternal health, with the launch of ZURZUVAE in the treatment of women with PPD. Not only are we seeing growing interest from HCPs to learn more about ZURZUVAE, but we believe the launch of ZURZUVAE is a catalyst for positive change in the screening, diagnosis, and treatment of PPD. We are seeing increased awareness and attention to PPD in the media and by professional organizations. This has increased knowledge about the cause of PPD and potential treatments and reduced stigma, making it easier for women to seek care.

Further, I'm excited to see ZURZUVAE being recognized amongst clinicians and OB-GYNs in particular as a distinct new treatment option for women with PPD. It has a novel MOA and is a rapidly-acting short course treatment with a flexible approach that gives HCPs the option to use ZURZUVAE alone or in combination with other therapies. In a short period of time, we believe we are starting to see PPD move from a disease where some HCPs would suspect the diagnosis and refer for evaluation and treatment, to a disease that HCPs are confident to diagnose and treat. Supporting mothers has always been a core focus for us, and we are excited we finally have an oral option for HCPs who want to offer more to women with PPD. In addition to the work that we do in PPD, we have many interesting programs in our pipeline.

Dalzanemdor, also referred to as SAGE-718, is a program that we are really excited about. We are advancing Dalzanemdor, our wholly owned first-in-class NMDA receptor positive allosteric modulator or PAM, as a potential oral therapy for cognitive disorders associated with neurodegenerative diseases, including cognitive impairment in Huntington's disease or HD, Parkinson's disease, PD, and Alzheimer's disease, AD. disorders with cognitive impairment represent some of the greatest areas of unmet need in medicine, and we know that globally they continue to increase in prevalence and pose significant challenges to patients in their everyday lives. The mechanism of action of Dalzanemdor is differentiated and leverages our deep understanding of how neuroactive steroids interact with the NMDA receptor.

A growing body of evidence suggests that NMDA receptor hypofunction may occur in a wide range of neurodegenerative disorders associated with cognitive impairment, including Huntington's, Parkinson's, and Alzheimer’s. Dalzanemdor is a novel molecule derived from our understanding of the pharmacology of a neuroactive steroid, 24s hydroxycholesterol, an endogenous NMDA receptor PAM. Dalzanemdor is believed to bind to the NMDA receptor, with the potential of modulating NMDA receptor activity to improve cognitive function. We are encouraged by the consistent effects on important domains of cognition, such as executive function and learning and memory that we've seen in our earlier studies in HC, PD, and AD, and we are excited to be progressing a clinical development program for Dalzanemdor, with five ongoing clinical trials.

Starting with HD, the lead indication for Dalzanemdor, we are currently enrolling in three studies in people with cognitive impairment due to Huntington's. The DIMENSION Study is a double-blind placebo-controlled Phase 2 study designed to evaluate the efficacy of one daily Dalzanemdor dosed over three months. The SURVEYOR study is a double-blind placebo-controlled Phase 2 study designed to generate evidence linking efficacy signals of cognitive performance to real-world functioning. And the PURVIEW study is an open-label Phase 3 safety study of Dalzanemdor designed to evaluate the long-term safety profile and long-term functioning compared to HD natural history studies. As a reminder, the primary objective of the SURVEYOR study is to understand the magnitude of the cognitive impairment in Huntington's relative to healthy individuals.

A key secondary objective is to advance our understanding of the effects of Dalzanemdor on cognition and function in participants with Huntington's. It's important to note that the SURVEYOR study is not designed or powered to show statistically significant differences between Dalzanemdor and placebo. Overall, these data are meant to complement the DIMENSION study by generating evidence to better define clinically meaningful change and the relationship between changes in cognition and function. Moving now to our PD and AD studies for Dalzanemdor. The PRECEDENT study is a double-blind placebo-controlled Phase 2 study in people with mild cognitive impairment due to Parkinson's disease designed to evaluate the safety and efficacy of Dalzanemdor.

The LIGHTWAVE study is a similarly designed Phase 2 study to evaluate safety and efficacy of Dalzanemdor in people with mild cognitive impairment and mild dementia due to AD. We expect to announce top line data from PRECEDENT for PD in early 2024, SURVEYOR for HD in mid-2024, and DIMENSION for HD, and LIGHTWAVE for AD, both in late 2024. We're very excited for these readouts, and if positive, they will help demonstrate a path forward for Dalzanemdor, and importantly, bring us one step closer to helping patients. Turning to SAGE-324, which is an investigational positive allosteric modulator of GABAA receptors with significant potential in the treatment of movement disorders like essential tremor. Essential tremor has suffered from a lack of innovation, with no new approved treatments in more than 50 years, and it has a significant impact on an individual's ability to perform everyday tasks.

In the US, the total annual estimated economic impact of essential tremor is over $100 billion, including medical, loss of employment, and disability costs. We are excited about the potential of SAGE 324 in essential tremor, a program that we are developing in collaboration with Biogen. As a reminder, the KINETIC study demonstrated statistically significant reductions in baseline in upper limb tremor amplitude. KINETIC 2 is a three-month study designed to identify a dose with a safety tolerability profile that is suitable for use of SAGE-324 as a chronic treatment in essential tremor. While the primary endpoint for KINETIC 2 is a change from baseline in upper limb tremor amplitude, we will also evaluate a modified version of the TETRAS ADL to give us directional insight into the effects of SAGE-324 on quality of life and activities of daily living.

We have completed enrollment of KINETIC 2 and expect to report topline data mid this year. Lastly, I'd like to share our excitement around the earlier stage pipeline. In particular, I'd like to highlight two novel molecules, SAGE-319, our extra-synaptic GABAA receptor PAM, and SAGE-421, our NMDA receptor PAM. We look forward to sharing more about these programs as they progress. In closing, I am proud of our pipeline efforts this year, and I look forward to our future progress and clinical execution throughout a catalyst-rich 2024. Now, I'll turn the call over for a review of our financials. Kimi?

Kimi Iguchi: Thanks, Laura. Our financial results for the fourth quarter and full year 2023 are detailed in our press release issued this morning. Before discussing specifics, I want to share my excitement on the recent launch of ZURZUVAE and the opportunity to help so many women suffering with PPD. I also want to thank the entire SAGE team for their continued execution and dedication to our mission to support brain health patients. We and Biogen have mobilized with the goal of continued commercial momentum, and are jointly supporting the planned launch of ZURZUVAE, with 50-50 cost sharing in the United States. While we're thinking big about the opportunity, we're executing with a focused approach and plan to scale with success.

In addition, we are prepared to execute on a catalyst-rich year ahead, with multiple expected top line data readouts for Dalzanemdor and SAGE-324. We're investing strategically in our broader pipeline to have the potential for value creation opportunities for the near, mid and long-term. I'll now turn to the financials. Today, we announced collaboration revenue from the initial sales of ZURZUVAE of $824,000. As a reminder, our reporting collaboration revenue is 50% of the net revenue Biogen reports for ZURZUVAE. Net revenues are recorded when Biogen ships ZURZUVAE to the distributors, and are not based on the number of prescriptions delivered from a specialty pharmacy to patients. ZURZUVAE net revenues in December 2023 principally represent initial efforts of preparing the channel for the full launch in the first quarter of 2024.

Additionally, today we announced milestone revenue of $75 million from Biogen related to the first commercial sale of ZURZUVAE for the treatment of PPD. We earned the milestone in Q4 and received payment in January 2024. We're not guiding on gross to net today, other than to say, given the fact that ZURZUVAE is a novel medication and the only approved oral treatment for women with PPD, we do not anticipate the type of discounting we see for other branded CNS agents. Turning to operating expenses, R&D expenses were $64.3 million in the fourth quarter of 2023. SG&A expenses were $55.1 million in the fourth quarter of 2023. The decrease in both R&D and SG&A expenses compared to the fourth quarter of last year was primarily related to reorganization cost-saving measures such as reduced headcount, budgeted expenditures, and prioritization of early pipeline programs.

We expect that operating expenses will decrease in 2024 relative to 2023. Cost of revenues for ZURZUVAE for the fourth quarter of 2023 included one-time charges in preparation for commercial availability. These one-time charges included distribution setup fees and charges for the manufacturing network. We do not expect this gross margin trend to continue. Our net loss for the fourth quarter of 2023 was $32.7 million, and we ended the fourth quarter of 2023 with cash, cash equivalents, and marketable securities of approximately $753 million. We are reaffirming that based on our current operating plan, we anticipate cash, cash equivalents, and marketable securities, along with a milestone payment received in January, anticipated funding from ongoing collaborations, and estimated revenues, will support operations into 2026.

I'd like to note that we have maintained a strong financial foundation as we enter a catalyst-rich year for the company. Before I turn the call over, I want to highlight the scope of our potential as a growing leader in brain health. The launch of ZURZUVAE demonstrates the culmination of our capabilities, starting from molecule discovery to FDA approval and now commercial launch. We look forward to the year ahead with many exciting catalysts across our pipeline and the continued commercialization of ZURZUVAE in the treatment of women with PPD. I'll now turn it over to Ashley to handle Q&A with the operator. Ashley?

Ashley Kaplowitz: Thanks, Kimi. I'll ask that you limit yourself to one question. If you have an additional question, additional question, feel free to return to the queue. Now I'll turn it over to the operator to handle Q&A. Operator?

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