Nav1.1

In February 2025, the global biopharmaceutical industry remains active in clinical-stage drug financing and collaboration activities. For instance, XtalPi Holdings successfully raised over HKD 3.2 billion via two equity placements, which will be used to further develop its AI+CRO business model. Additionally, in the realm of innovative drug partnership deals, CSPC Group’s subsidiary signed an exclusive licensing agreement with Radiance Biopharma for the antibody-drug conjugate (ADC) SYS6005, which includes up to $150 million in potential development and regulatory milestone payments as well as up to $1.075 billion in potential sales milestone payments. Innovent Biologics outlined a global exclusive collaboration and licensing agreement with Roche for the next-generation ADC candidate IBI3009, with potential milestone payments reaching up to $1 billion. 1. Nxera Pharma and Viatris Collaborate to Advance the Development and Commercialization of an S1P1 Receptor Modulator in the Asia-Pacific Region On February 28, 2025, Nxera Pharma reached a significant agreement with Viatris Inc. and Idorsia Pharmaceuticals Ltd regarding the rights to develop and commercialize Cenerimod in Japan, South Korea, and other Asia-Pacific regions (excluding China). Cenerimod, a novel oral S1P1 receptor modulator, holds significant potential as a first-line or best-in-class therapy for various autoimmune diseases. Under the terms of the agreement, Nxera Pharma will receive an upfront payment of $10 million from Viatris and will be eligible for regulatory milestone payments upon Cenerimod's approval in Japan. Additionally, Nxera Pharma will collect royalties based on net sales within the designated territories. Cenerimod is a highly selective S1P1 receptor modulator that primarily works by controlling lymphocyte migration to reduce inflammation. Prior to this, Viatris had already secured exclusive global rights to develop and commercialize Cenerimod outside of Japan and the Asia-Pacific region (excluding China) through a 2024 research and development agreement with Idorsia. This new partnership with Nxera Pharma further reinforces Viatris's global positioning in drug development and provides robust support for Cenerimod's ongoing research and development. The mechanism of Cenerimod lies in its selective targeting of the S1P1 receptor. By inhibiting lymphocyte egress from peripheral lymphoid organs into systemic circulation, Cenerimod effectively suppresses inflammatory responses. This allows it to address the abnormally elevated levels of type I interferons (IFN-1) and other pro-inflammatory cytokines observed in autoimmune diseases such as systemic lupus erythematosus (SLE). This collaboration underscores the critical role of cross-company partnerships in accelerating the development of innovative medicines. It not only expedites market entry for novel drugs to meet unmet medical needs but also effectively distributes research and development risks, fostering sustainable growth within the pharmaceutical industry. For Cenerimod, this collaboration promises broader market access and technical support, paving the way for potential breakthroughs in the treatment of autoimmune diseases. 2. Shuangqi Pharmaceutical and Anaerobic Biotechnology Collaborate to Advance the Development and Commercialization of a Quadrivalent Lactobacillus Vaginal Live Biotherapeutic Capsule Inner Mongolia Shuangqi Pharmaceutical has entered into a significant agreement with Anaerobic Biotechnology concerning an innovative live biotherapeutic product, KAL-001, for vaginal use. This microecological therapy aims to restore a healthy vaginal environment by regulating its microbiota, specifically targeting vaginal inflammatory conditions in women of reproductive age. KAL-001 is composed of four specific strains of Lactobacillus, identified after a complex process of screening, isolation, preservation, and evaluation by Anaerobic Biotechnology. KAL-001 works by replenishing beneficial bacterial flora, i.e., Lactobacillus, in the vagina to restore and maintain a healthy microbial balance. This therapeutic approach differs from traditional antibiotic treatments. Instead of directly killing pathogens, it inhibits the growth of harmful microorganisms by increasing the population of beneficial microbes. Lactobacilli produce metabolic byproducts such as lactic acid, which lower vaginal pH and create an inhospitable environment for pathogenic organisms. Additionally, Lactobacillus may competitively exclude other potential pathogens and enhance the host’s local immune response through immunomodulatory mechanisms. The collaboration extends beyond product development and includes the transfer of commercialization rights. According to the licensing agreement, Shuangqi Pharmaceutical will pay Anaerobic Biotechnology an upfront fee of RMB 25 million and commit to milestone payments of up to RMB 170 million based on development progress and sales performance, along with royalties derived from net sales. This arrangement reflects the confidence both parties have in the market potential of KAL-001 and highlights their commitment to supporting R&D investments. 3. Sino Biopharmaceutical Collaborates with Sciwind Biosciences to Advance the IL-29 Project; CPX102 Expected to Become a Breakthrough Treatment for RSV Sino Biopharmaceutical has announced the signing of an exclusive strategic collaboration agreement with Sciwind Biosciences for the development and commercialization of the human interleukin-29 (IL-29, also known as interferon-λ1) project. The deal grants exclusive licensing and cooperation rights in 19 countries, including China (including Hong Kong, Macau, and Taiwan), Brazil, Saudi Arabia, Thailand, and Singapore. The partnership aims to expedite the development of CPX102 and expand its applications in the global market. CPX102 is an inhalable aerosol solution developed through protein engineering based on IL-29. As a type III interferon, it does not directly kill or inhibit viruses but induces antiviral protein production by activating cell surface receptors, thereby preventing viral replication. Additionally, it can activate immune cells, such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, thus enhancing the body's innate immune response against viral infections. This treatment is particularly effective for respiratory syncytial virus (RSV) infections in children, as it directly targets the epithelial cells in the lungs via inhalation, allowing for rapid onset of action and significantly improving the clearance of the virus. As the world's first aerosolized inhalation medication for RSV treatment, CPX102 offers high patient acceptability, particularly for children. Its local administration results in systemic exposure that is only about 1/100 of the injection dosage, drastically reducing the occurrence of systemic side effects. This not only helps avoid the discomfort associated with injections but also makes the treatment process safer and more comfortable, an especially critical factor for pediatric patients with pulmonary viral infections. As a broad-spectrum antiviral drug, CPX102 activates the host immune system to clear various respiratory viruses, including RSV, SARS-CoV-2, and influenza viruses, and is not affected by viral mutations. Given the current lack of effective treatments for RSV, particularly in high-incidence countries like China, CPX102 has vast market potential. It is estimated that RSV causes approximately 330 million respiratory infections globally each year, with China being one of the countries with the highest incidence rate. Currently, CPX102 is undergoing Phase IIb clinical trials in China and is expected to become the first Class 1 innovative drug in the country approved for the nebulized treatment of RSV infections in children. Considering the unmet demand for RSV therapies both in China and globally, along with the promising clinical results of CPX102, this drug has the potential to become a blockbuster product in the respiratory and anti-infective therapeutic area, bringing tremendous market value and social benefits. 4. Ligand Pharmaceuticals Invests $75 Million to Support Castle Creek Biosciences’ D-Fi Gene Therapy On February 25, Ligand Pharmaceuticals announced the completion of a $75 million royalty financing agreement with Castle Creek Biosciences to fund the Phase III clinical development of D-Fi (FCX-007), a gene therapy for dystrophic epidermolysis bullosa (DEB), through its initial data readouts. Of the $75 million investment, Ligand provided $50 million, while leading a consortium—including Paragon Biosciences, Valor Equity Partners, and new investor XOMA Royalty Corporation—that contributed the remaining $25 million. In return, the investors will receive single-digit percentage royalties on global sales of D-Fi. D-Fi is an autologous gene-modified cell therapy designed to treat DEB, a rare genetic skin disorder caused by mutations in the COL7A1 gene. This condition results in insufficient production of type VII collagen (COL7), which is critical for anchoring the dermis to the epidermis. To address this, D-Fi uses dermal fibroblasts harvested from the patient, modifies them ex vivo with a self-inactivating (SIN) lentiviral vector encoding the COL7A1 gene to produce COL7 protein, and locally injects the treated cells into chronic wounds. This promotes the formation of anchoring fibrils within the skin. Clinical studies have shown that D-Fi is well-tolerated, with the primary adverse reactions being localized injection site responses. This collaboration underscores Ligand's commitment to investing in breakthrough treatments that have the potential to transform patients’ lives while also diversifying its income-generating asset portfolio. Matthew Gantz, President and CEO of Castle Creek Biosciences, expressed support for the partnership, emphasizing its significance as a critical step towards addressing the unmet needs of patients with DEB. 5. Eli Lilly Acquires Organovo's FXR Program, Including Key Therapy FXR314 On February 25, 2025, Organovo Holdings announced that Eli Lilly and Company would acquire its FXR program, including its core asset FXR314. This transaction marks a significant milestone for Organovo in advancing drug development for inflammatory bowel disease (IBD) using their proprietary 3D human tissue models. FXR314 is a potentially "best-in-class" oral farnesoid X receptor (FXR) agonist, initially developed to target metabolic dysfunction-associated steatohepatitis (MASH). However, recognizing the immense market potential of inflammatory bowel disease and the limitations of existing therapeutic options, Organovo deemed FXR314 equally compelling for the IBD space. Preclinical studies have demonstrated that FXR314 improves key indicators of ulcerative colitis in a dose-dependent manner using an adoptive T-cell transfer model. Under the agreement terms, Organovo will receive an upfront payment from Eli Lilly, in addition to milestone payments as FXR314 progresses through critical regulatory and commercial achievements. Moreover, Eli Lilly will obtain worldwide rights to develop and commercialize Organovo’s FXR program, including all associated intellectual property. Organovo anticipates reporting results from the Phase IIa clinical trial of FXR314 for ulcerative colitis in the first half of 2026. Through this acquisition, Eli Lilly not only strengthens its portfolio in the inflammatory bowel disease field but also underscores its commitment to innovative therapies. Previously, Eli Lilly successfully launched the IL-23 monoclonal antibody Mirikizumab for treating ulcerative colitis and Crohn’s disease, achieving significant results. With the addition of FXR314 from Organovo, Eli Lilly is well-positioned to further expand its impact in IBD treatment, offering new hope to patients. 6. CARsgen Therapeutics Partners with SoftBank Xinchuang to Accelerate the Development of Off-the-Shelf CAR-T Cell Therapies in China On February 25, 2025, CARsgen Therapeutics announced a strategic partnership with SoftBank Xinchuang, jointly investing in Ukaize Biopharmaceuticals. This collaboration aims to accelerate the development and commercialization of CARsgen’s two off-the-shelf CAR-T cell therapy products in mainland China. These products include a BCMA CAR-T therapy targeting multiple myeloma and plasma cell leukemia, as well as a CD19/CD20 CAR-T therapy for B-cell malignancies. Through this partnership, CARsgen seeks to leverage external capital to expedite innovation in the CAR-T therapy field. As part of the agreement, a SoftBank Xinchuang-managed fund will subscribe to RMB 80,000,000 of newly issued registered capital in Ukaize Biopharmaceuticals, acquiring an 8% equity stake upon transaction completion. This financing not only provides essential funds for Ukaize but also reduces CARsgen’s ownership in Ukaize from 100% to 92%. The capital investment will be allocated to support Ukaize’s research, production, and commercialization efforts. For a rapidly evolving biotech company, such funding is vital to advancing clinical trials and shortening the time required to bring new products to market. CARsgen’s two CAR-T cell therapy products target key molecular markers: BCMA (B-cell maturation antigen) and CD19/CD20. The BCMA CAR-T therapy is primarily designed to treat multiple myeloma and plasma cell leukemia—both of which are challenging, refractory hematologic malignancies. Meanwhile, the CD19/CD20 CAR-T therapy is developed to combat B-cell-derived malignancies. These therapies work by genetically engineering patients' T cells to recognize and destroy cancer cells, offering a new form of personalized treatment. This approach represents a significant advancement in the field of cancer treatment by enabling precision-targeted therapy against cancer cells while minimizing damage to normal tissues. 7. CSPC Licenses ROR1-Targeting ADC to Radiance Biopharma On February 19, 2025, CSPC Pharmaceutical Group announced that it has granted Radiance Biopharma exclusive rights for the development and commercialization of its proprietary ROR1-targeting antibody-drug conjugate (ADC), SYS6005, in the United States and other major markets. Under the terms of the agreement, Radiance Biopharma will pay an upfront fee of $15 million, with additional development and regulatory milestone payments of up to $150 million, and sales milestone payments totaling up to $1.075 billion. Furthermore, Radiance Biopharma will pay tiered royalties based on the annual net sales of the product in the licensed territories. This collaboration marks another major milestone for CSPC in its global market expansion. SYS6005 is a monoclonal antibody-drug conjugate specifically designed to bind to the ROR1 receptor on the surface of tumor cells. Through endocytosis, the ADC delivers the potent mitotic inhibitor MMAE into cancer cells, where it releases its cytotoxic payload to effectively kill the cancer cells. This targeted design enhances therapeutic efficacy while minimizing damage to healthy tissues. SYS6005 received approval from the Chinese National Medical Products Administration (NMPA) to enter clinical trial stages by the end of 2024, with indications including hematological malignancies, ovarian cancer, non-small cell lung cancer, and other advanced malignancies. These developments highlight the broad potential application of SYS6005 in oncology. 8. Brexogen and BMI Korea Enter Technology Transfer Agreement for Exosome-Based Therapy On February 19, 2025, Brexogen, a biotechnology company specializing in exosome-based therapies, announced a technology transfer and licensing agreement with BMI Korea for its innovative injectable therapeutic, BxC-I17e. BxC-I17e, an exosome-based therapy currently undergoing clinical trials for the treatment of atopic dermatitis in the United States, is at the forefront of Brexogen’s pipeline. Under the terms of the agreement, BMI Korea gains rights to develop additional potential indications, excluding immune-related diseases, for domestic and major export markets. Financially, Brexogen will receive a non-refundable upfront payment of 30 billion KRW (approximately $23 million) and will be eligible for milestone payments tied to clinical, regulatory, and commercial achievements, alongside double-digit percentage royalties on net annual sales. Additionally, if BMI Korea enters sublicensing agreements with third parties, Brexogen will share in the resultant licensing revenues. BMI Korea, a company generating over 100 billion KRW in annual revenue, brings robust pharmaceutical manufacturing capabilities, ensuring high-quality and scalable production for BxC-I17e. BxC-I17e is a key asset in Brexogen's pipeline, leveraging the company’s proprietary exosome technology, which allows precise control over the therapeutic cargo carried by exosomes to enable targeted disease treatment. Currently undergoing Phase I clinical trials for atopic dermatitis, BxC-I17e demonstrates broad therapeutic potential. BMI Korea plans to explore its application in indications outside the immunology field, offering promising new therapeutic possibilities. At present, no exosome-based therapies have received commercial approval globally, making this collaboration a significant step forward in advancing innovation in exosome therapeutic development and setting new benchmarks within the industry. Brexogen is not only exploring dermatological treatments with BxC-I17e but has already successfully commercialized products like BREXTEM-S for skin regeneration and BREXTEM-H for hair restoration. Looking ahead, Brexogen is preparing for its anticipated 2026 IPO on KOSDAQ, which is expected to accelerate the clinical and commercial adoption of exosome-based therapies. 9. Biogen and Stoke Therapeutics Collaborate on Developing a Treatment for Dravet Syndrome On February 18, 2025, Biogen and Stoke Therapeutics announced a collaboration to develop and commercialize zorevunersen, a potentially first-in-class therapeutic for the treatment of Dravet syndrome. Dravet syndrome is a rare genetic epilepsy disorder characterized by treatment-resistant seizures and neurodevelopmental delays. Under the agreement, Stoke will continue to lead global development and retain exclusive development and commercialization rights in the U.S., Canada, and Mexico, while Biogen will have exclusive commercialization rights in other territories worldwide. The partnership leverages Biogen’s extensive expertise in neurological disorders and its global commercialization capabilities, aiming to bring new therapeutic hope to patients with Dravet syndrome. As part of this collaboration, Stoke will receive an upfront payment of $165 million, and both companies will share external clinical development costs, with Biogen contributing 30% and Stoke covering 70%. Additionally, Stoke is eligible for up to $385 million in development and commercial milestone payments. If zorevunersen achieves commercial success globally, Stoke will receive tiered royalties on net sales, ranging from low double digits to high teens. This financial structure not only provides Stoke with the necessary funding support but also lays the groundwork for subsequent research and development activities. Zorevunersen is an investigational antisense oligonucleotide (ASO) targeting the SCN1A gene, which is the root cause of most Dravet syndrome cases. The drug has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) based on preliminary clinical evidence suggesting it can provide significant improvements unmet by existing therapies. In Phase I/IIa and open-label extension (OLE) studies, patients treated with zorevunersen experienced a sustained reduction in the frequency of convulsive tonic-clonic seizures, as well as improvements across multiple cognitive and behavioral metrics. These findings support the potential for zorevunersen to progress to pivotal global Phase III trials, potentially becoming the first treatment to alter the course of Dravet syndrome. Currently, there are no approved disease-modifying therapies for Dravet syndrome, making the development of zorevunersen highly significant. The pivotal Phase III EMPEROR trial is expected to commence in the second quarter of 2025, with primary data readouts anticipated in the second half of 2027 to support global regulatory submissions. This progress is crucial for addressing the significant unmet medical needs of patients with Dravet syndrome and may herald a new era in the treatment of severe genetic disorders. 10. Foundation Medicine Partners with Sumitomo Pharma America to Advance Innovative Treatments for Acute Leukemia On February 18, 2025, Foundation Medicine, a genomics company dedicated to transforming cancer care, announced a collaboration with Sumitomo Pharma America (SMPA) to develop FoundationOne® Heme as a companion diagnostic tool to identify acute leukemia patients with KMT2A rearrangements or NPM1 mutations. These patients may be eligible for treatment with SMPA’s investigational menin inhibitor, enzomenib (DSP-5336). The collaboration aims to leverage advanced comprehensive genomic analysis to develop novel targeted therapies for hematologic malignancies. Acute leukemia is a condition requiring urgent intervention due to its rapid proliferation of blood cells, leading to the swift onset of symptoms. Approximately 30% of acute myeloid leukemia (AML) patients carry NPM1 mutations, while 5–10% of AML patients present with KMT2A (MLL) rearrangements. Menin inhibitors are gaining focus as a targeted therapeutic option for these specific genetic alterations. Menin plays a critical role in regulating hematopoiesis through its interaction with the KMT2A gene. The mechanism of action of menin inhibitors involves disrupting this protein-protein interaction, thereby inhibiting the proliferation of leukemia cells. Enzomenib (DSP-5336), developed by Sumitomo Pharma, is a menin inhibitor designed to treat patients with KMT2A rearrangements or NPM1 mutations in acute leukemia. The drug works by interrupting the interaction between menin and KMT2A, aiming to inhibit the growth of leukemia cells. Preclinical studies have shown promising results for this therapeutic approach in patients with the aforementioned genetic variants. This partnership is expected to drive the development of enzomenib and accelerate its clinical application. The FoundationOne® Heme platform combines DNA sequencing with RNA sequencing technologies, enabling the detection of all types of genomic alterations, including base substitutions, insertions and deletions, copy number variations, and gene fusions. This platform provides physicians with testing options for both blood and tissue samples, helping tailor personalized treatment plans based on a patient's specific genomic alterations. Read the Rest of the Series Highlights of February 2025: Biopharmaceutical Clinical-Stage Drug Investment, Financing, and Collaboration Deals (2) How to get the latest progress on drug deals? If you would like to access the latest transaction event information, you can click on the 'Deal' module from the homepage of the Synapse database. Within the Deal module, you can search for global pharmaceutical transaction information using labels such as Drugs, Organization, Target, Drug Type, Deal Date.  Furthermore, you can obtain the original link to the transaction coverage by clicking on the "Deal Name." In the analysis view, you can see the most active assignors, assignees, popular targets, and other dimensions of analysis, as well as the distribution of research and development statuses at the time of the transaction, to help you better understand the search results. The Synapse database also supports the ability to view current transactions from the dimension of "drugs" (by selecting "drugs" from the "Adjust Dimension" dropdown menu above). Targeting transactions involving renowned pharmaceutical companies that are of interest to the industry, such as Merck, Roche, etc., Synapse has identified a group of "leading companies" through drugs that have achieved global sales exceeding 1 billion US dollars in 2022. Transactions involving drugs from these leading companies can be filtered by clicking on the "Leading Company" tag on the left-hand side. In addition to the drug transaction module, you can also view related transaction history on the drug detail page and the institution detail page. Click on the image below to explore new pharmaceutical funding transactions! 

– Phase 3 topline data from azetukalner FOS epilepsy program planned for H2 2025 in support of NDA filing and potential commercial launch – First of three planned Phase 3 azetukalner MDD studies underway, with second study on track to initiate mid-year – Phase 3 azetukalner bipolar depression program planned for clinical trial initiation mid-year – Early-stage portfolio advancing with Kv7 and Nav1.7 IND filings anticipated in 2025 – Neurocrine collaboration achieves milestone with initiation of Phase 1 study of Nav1.2/Nav1.6 inhibitor – Conference call at 4:30 pm ET today VANCOUVER, British Columbia and BOSTON, Feb. 27, 2025 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq: XENE), a neuroscience-focused biopharmaceutical company dedicated to discovering, developing, and delivering life-changing therapeutics for patients in need, today provided a business update and reported financial results for the fourth quarter and full year ended December 31, 2024. “We expect the next 12 to 24 months will represent a catalyst-rich period for Xenon as we continue to advance our deep pipeline of promising late- and early-stage programs across multiple neurological and neuropsychiatric indications. The anticipated readout from our Phase 3 study in focal onset seizures signifies an important inflection point and could set the stage for our first potential commercial product launch in epilepsy. In addition to building upon our growing leadership in the epilepsy community, we firmly believe that azetukalner has broad potential in neuropsychiatric indications based upon strong mechanistic and scientific rationale, and we are pleased to be enrolling patients in our Phase 3 MDD program, with plans to now initiate a registrational program studying the use of azetukalner in bipolar depression,” said Ian Mortimer, President and Chief Executive Officer of Xenon. “We also expect multiple regulatory filings in 2025 coming out of our early-stage portfolio – which includes Kv7 and Nav1.7 candidates that are progressing through IND-enabling studies – to support the initiation of first-in-human trials across multiple targets. In addition, we are pleased to confirm a promising Nav1.2/Nav1.6 sodium channel inhibitor discovered in Xenon labs has progressed into a Phase 1 study as part of our collaboration with Neurocrine Biosciences, triggering a milestone payment to us,” stated Mr. Mortimer. Business Highlights and Anticipated Milestones Azetukalner Clinical Development Azetukalner, a novel, highly potent, selective Kv7 potassium channel opener, represents the most advanced, clinically validated potassium channel modulator in late-stage clinical development for the treatment of multiple indications that include epilepsy, including focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS), as well as neuropsychiatric disorders including major depressive disorder (MDD) and bipolar depression (BPD). Epilepsy Programs Phase 3 X-TOLE2/3 azetukalner clinical studies in FOS continue to advance, with the first topline data readout anticipated in the second half of 2025. Phase 3 X-ACKT clinical study continues to enroll patients and is intended to support potential regulatory submissions in an additional epilepsy indication of PGTCS. Building upon more than 700+ patient-years of data to date from the ongoing X-TOLE open-label extension (OLE) study, Xenon continues to generate long-term scientific evidence supporting azetukalner’s compelling efficacy and safety profile, with approximately one in three patients on drug for at least 36 months achieving seizure freedom for a period of one year or longer. Xenon continues to present data at leading medical conferences, including the upcoming medical congresses of the American Society for Experimental Neurotherapeutics (ASENT) and the American Academy of Neurology (AAN) taking place in the first half of this year. Neuropsychiatric Programs X-NOVA2, the first of three planned Phase 3 clinical trials evaluating azetukalner in patients with MDD is currently enrolling patients, and X-NOVA3 is expected to initiate mid-year. Xenon announces plans for a Phase 3 BPD program with initiation of the first of two azetukalner clinical studies in bipolar I and bipolar II depression expected by mid-year. Initiation of this program is based on a strong scientific rationale – supported by promising clinical data with azetukalner and the Kv7 mechanism in MDD and preclinical research examining the genetic links between BPD and Kv7 and evidence of Kv7 downregulation in BPD – as well as a large unmet medical need. Patient enrollment in the investigator-sponsored Phase 2 proof-of-concept study of azetukalner in MDD led by Icahn School of Medicine at Mount Sinai is complete, and topline results are anticipated in the first half of 2025. Early-Stage Pipeline: Next Generation Ion Channel Modulators Xenon continues to expand its portfolio by leveraging its extensive expertise to discover and develop potassium and sodium channel therapeutics, with the goal of filing multiple INDs, or equivalent, in 2025. IND-enabling work is underway with multiple Kv7 development candidates. Kv7 may have utility in a broad range of therapeutic indications including seizures, pain, and neuropsychiatric disorders, such as MDD and BPD. IND-enabling work is underway with a lead Nav1.7 development candidate. Nav1.7 is an important pain-related target, based on strong human genetic validation, that may represent a new class of medicines without the limitations of opioids. The Company expects a lead candidate within its Nav1.1 program will enter IND-enabling studies in 2025. Pre-clinical data suggests that targeting Nav1.1 could potentially address the underlying cause and symptoms of Dravet Syndrome. Partnered Program As part of Xenon’s ongoing collaboration with Neurocrine Biosciences to develop treatments for epilepsy, NBI-921355, a Nav1.2 and Nav1.6 sodium channel inhibitor in development for the potential treatment for certain types of epilepsy, has progressed into a Phase 1 clinical study in healthy adult participants, triggering an anticipated $7.5 million milestone payment to Xenon. Corporate Xenon announced that Sherry Aulin plans to step down as Chief Financial Officer due to personal reasons. Ms. Aulin is expected to continue to serve as CFO until June 30, 2025, and then act as an advisor through the end of August to ensure a smooth transition. “Sherry has made invaluable contributions to the organization over the last decade and was instrumental in helping build Xenon as we evolved from a discovery organization to what is now a late-stage clinical organization readying for our first potential drug approval and commercial launch,” said Mr. Mortimer. “On behalf of the Board and our entire Xenon team, I want to thank Sherry for her successful leadership as CFO and commitment to ensure a smooth transition at this important time for the company.” “While I am stepping down for personal reasons, I remain excited about Xenon’s future, as it enters this transformational period driving towards commercialization, as well as the significant impact Xenon’s therapeutics could potentially have on the lives of patients around the world. It has been a privilege to serve as CFO of Xenon, and I am truly honored to have worked alongside such a talented team, and very confident that Xenon is positioned for success,” said Ms. Aulin. Fourth Quarter & Full Year Financial Results Cash and cash equivalents and marketable securities were $754.4 million as of December 31, 2024, compared to $930.9 million as of December 31, 2023. Based on current operating plans, including the completion of the azetukalner Phase 3 epilepsy studies and supporting late-stage clinical development of azetukalner in MDD and BPD, Xenon anticipates having sufficient cash to fund operations into 2027. As of December 31, 2024, there were 76,416,086 common shares and 2,173,081 pre-funded warrants outstanding. Research and development expenses were $59.5 million for the fourth quarter of 2024, and $210.4 million for the year ended 2024, compared to $41.1 million and $167.5 million for the same periods in 2023, respectively. The increase in research and development expenses for the year was primarily attributable to the azetukalner program and increased expenses related to the ongoing Phase 3 epilepsy clinical trials, the initiation of the first Phase 3 MDD clinical trial, as well as manufacturing activities to support current and future clinical trials and a potential NDA submission, and increased personnel-related costs due to an increase in employee headcount and higher stock-based compensation expense. General and administrative expenses were $18.0 million for the fourth quarter of 2024, and $68.9 million for the year ended 2024, compared to $12.6 million and $46.5 million for the same periods in 2023, respectively. The increase in general and administrative expenses for the year was primarily attributable to personnel-related costs due to an increase in employee headcount and higher stock-based compensation expense, and an increase in professional and consulting fees. Other income was $7.9 million for the fourth quarter of 2024, and $40.9 million for the year ended 2024, compared to $8.7 million and $31.4 million for the same periods in 2023. The increase in other income for the year was primarily attributable to higher interest income. Net loss was $65.7 million for the fourth quarter of 2024, and $234.3 million for the year ended 2024, compared to $44.7 million and $182.4 million for the same periods in 2023, respectively. The increase in net loss for the year was primarily attributable to higher research and development expenses driven by the azetukalner program, as well as increased personnel-related costs and stock-based compensation expense across the organization, partially offset by an increase in interest income. Conference Call Information Xenon will host a conference call and webcast today at 4:30 pm Eastern Time (1:30 pm Pacific Time) to discuss its fourth quarter and full year 2024 results. A listen-only webcast can be accessed on the Investors section of the Xenon website, with a replay available following the event. Participants can access the conference call by dialing (800) 715-9871 or (646) 307-1963 for international callers and referencing conference ID 8120798. About Azetukalner Phase 3 Epilepsy Program Xenon’s Phase 3 epilepsy program includes three Phase 3 clinical trials in focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS). Designed closely after the Phase 2b X-TOLE clinical trial, the Phase 3 X-TOLE clinical trials are multicenter, randomized, double-blind, placebo-controlled studies evaluating the clinical efficacy, safety, and tolerability of 15 mg or 25 mg of azetukalner administered orally with food as adjunctive treatment in approximately 360 patients with FOS per study. The primary efficacy endpoint is the median percent change (MPC) in monthly seizure frequency from baseline through the 12-week double-blind period (DBP) of azetukalner compared to placebo. X-ACKT is a multicenter, randomized, double-blind, placebo-controlled study evaluating the clinical efficacy, safety, and tolerability of 25 mg of azetukalner administered with food as adjunctive treatment in approximately 160 patients with PGTCS. The primary efficacy endpoint is the MPC in monthly PGTCS frequency from baseline through the 12-week DBP of azetukalner compared to placebo. Upon completion of the DBP in the Phase 3 epilepsy studies, eligible patients may enter an OLE study for up to three years. About Azetukalner Phase 3 MDD Program Xenon’s Phase 3 MDD program includes three multicenter, randomized, double-blind, placebo-controlled clinical trials to evaluate the clinical efficacy, safety, and tolerability of 20 mg of azetukalner administered orally with food over the 6-week double-blind period (DBP) as monotherapy treatment in approximately 450 patients with moderate-to-severe major depressive disorder (MDD) per study. The primary efficacy endpoint is the change from baseline in the HAM-D17 score at week 6 in patients who received azetukalner compared to placebo. Upon completion of the DBP, eligible patients may enter an OLE study for up to 12 months. About Xenon Pharmaceuticals Inc. Xenon Pharmaceuticals (Nasdaq: XENE) is a neuroscience-focused biopharmaceutical company dedicated to discovering, developing, and delivering life-changing therapeutics. We are advancing an ion channel product portfolio to address areas of high unmet medical need, including epilepsy and depression. Azetukalner, a novel, highly potent, selective Kv7 potassium channel opener, represents the most advanced, clinically validated potassium channel modulator in late-stage clinical development for multiple indications. For more information, please visit www.xenon-pharma.com. Safe Harbor Statement This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995 and Canadian securities laws. These forward-looking statements are not based on historical fact, and include statements regarding the timing of and potential results from clinical trials; the potential efficacy, safety profile, future development plans in current and anticipated indications, addressable market, regulatory success and commercial potential of our and our partners’ product candidates; the efficacy of our clinical trial designs; our ability to successfully develop and achieve milestones in our azetukalner and other pipeline and development programs, including the anticipated filing of INDs and NDAs; the timing and results of our interactions with regulators; our ability to successfully develop and obtain regulatory approval of azetukalner and our other product candidates; and anticipated timing of topline data readout from our clinical trials of azetukalner. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause the actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical trials may not demonstrate safety and efficacy of any of our or our collaborators’ product candidates; promising results from pre-clinical development activities or early clinical trial results may not be replicated in later clinical trials; our assumptions regarding our planned expenditures and sufficiency of our cash to fund operations may be incorrect; our ongoing discovery and pre-clinical efforts may not yield additional product candidates; any of our or our collaborators’ product candidates, including azetukalner, may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; regulatory agencies may impose additional requirements or delay the initiation or completion of clinical trials; the impact of market, industry, and regulatory conditions on clinical trial enrollment; the impact of competition; the impact of expanded product development and clinical activities on operating expenses; the impact of new or changing laws and regulations; the impact of unstable economic conditions in the general domestic and global economic markets; adverse conditions from geopolitical events; as well as the other risks identified in our filings with the U.S. Securities and Exchange Commission and the securities commissions in British Columbia, Alberta, and Ontario. These forward-looking statements speak only as of the date hereof and we assume no obligation to update these forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. “Xenon” and the Xenon logo are registered trademarks or trademarks of Xenon Pharmaceuticals Inc. in various jurisdictions. All other trademarks belong to their respective owner. Contacts: For Investors: Chad Fugere Vice President, Investor Relations (857) 675-7275 investors@xenon-pharma.com For Media: Colleen Alabiso Senior Vice President, Corporate Affairs (617) 671-9238 media@xenon-pharma.com Source: Xenon Pharmaceuticals Inc.

WAKIX® (pitolisant) Net Revenue of $201.3 Million for Fourth Quarter and $714.7 Million for Full Year 2024; Representing Growth of 23% in Year-Five on the Market 2025 WAKIX Net Revenue Guidance Between $820 - $860 Million ; On Track toward a Potential $1 Billion+ Opportunity Committed to Leadership in Sleep/Wake with Next Generation Pitolisant Formulations and Orexin 2 Receptor Agonist; Phase 3 Registrational Trials with Pitolisant HD in Narcolepsy and IH to Initiate in Q4 2025 Topline Data Readout from Phase 3 Registrational Trial with ZYN002 in Fragile X Syndrome On Track for Q3 2025 Pitolisant Patent Position Strengthened with Favorable Settlement of First Generic Litigation Conference Call and Webcast to be Held Today at 8:30 a.m. ET PLYMOUTH MEETING, Pa. --(BUSINESS WIRE)--Feb. 25, 2025-- Harmony Biosciences Holdings, Inc. (Nasdaq: HRMY) today announced a record $201.3 million in net product revenues for the fourth quarter 2024, and full year 2024 net revenues of $714.7 million , ending the year with $576 million in cash, cash equivalents and investments on the balance sheet. The company has guided 2025 WAKIX® net revenues to $820 - $860 million , targeting a $1B+ opportunity with WAKIX in narcolepsy alone. “2025 is set up to be a transformational year for Harmony, as our robust, late-stage pipeline comes into focus and we advance our long-term growth strategy,” said Jeffrey M. Dayno , M.D., President and Chief Executive Officer of Harmony Biosciences . “This year will bring major milestones for Harmony, with the topline data readout from our Phase 3 registrational trial with ZYN002 in Fragile X syndrome expected in Q3 and the potential, if successful, to bring the first approved treatment to the Fragile X patient community. In Q4, we will be initiating two Phase 3 registrational trials with our next gen Pitolisant HD formulation in both narcolepsy and idiopathic hypersomnia, potentially extending the pitolisant franchise out to the 2040s and further solidifying our leadership in sleep/wake. Taken together, these catalysts underscore the importance of 2025 as a pivotal year in Harmony’s long-term growth strategy. With at least one new product candidate or indication launch each year over the coming years, our pipeline has the potential to deliver over $3 billion in net revenue as the leading CNS company focused on developing and delivering innovative treatments for patients with unmet needs.” Franchise Highlights Sleep/Wake Franchise WAKIX in Narcolepsy Net Sales were $201.3M for Q4 2024 and $714.7M for FY 2024 2025 Net Revenue projected between $820 to $860 million Settlement reached in first Abbreviated New Drug Application (ANDA) litigation, giving Novugen Pharma a license to sell its generic product beginning in January 2030 or earlier under certain circumstances This settlement reinforces the strength and durability of Harmony’s intellectual property portfolio and its vigorous defense of its patent estate On track to obtain pediatric exclusivity which, if granted, would add an additional 6 months of regulatory exclusivity This settlement reinforces the strength and durability of Harmony’s intellectual property portfolio and its vigorous defense of its patent estate Pitolisant HD (high-dose) Higher dose and optimized pharmacokinetic profile designed to address the need for greater efficacy in excessive daytime sleepiness (EDS) and other symptoms in patients with central disorders of hypersomnolence Phase 3 registrational trial in narcolepsy to include endpoint on narcolepsy-related fatigue in pursuit of differentiated label Trial to initiate in Q4 2025; topline data readout anticipated in 2027 with potential PDUFA date in 2028 Phase 3 registrational trial in IH to include endpoint on sleep inertia in pursuit of differentiated label Trial to initiate in Q4 2025; topline data readout anticipated in 2027 with potential PDUFA date in 2028 Provisional IP filed out to 2044 for narcolepsy and IH Trial to initiate in Q4 2025; topline data readout anticipated in 2027 with potential PDUFA date in 2028 Trial to initiate in Q4 2025; topline data readout anticipated in 2027 with potential PDUFA date in 2028 Pitolisant GR (gastro-resistant) Pivotal bioequivalence study on track to initiate Q1 2025 Topline data readout anticipated in Q3 2025 with potential PDUFA in 2026 Provisional IP filed out to 2044 Topline data readout anticipated in Q3 2025 with potential PDUFA in 2026 Orexin-2 receptor agonist (BP1.15205) Potential to be best-in-class orexin-2 receptor agonist based on a novel chemical scaffold, preclinical potency, selectivity and safety data, as well as its potential for once-a-day dosing Preclinical safety and efficacy data to be presented at SLEEP 2025 (June) IMPD submission on track for mid-2025; first-in-human study expected to initiate 2H 2025 Neurobehavioral Franchise ZYN002 Innovative product profile: pharmaceutically manufactured synthetic cannabidiol devoid of THC The RECONNECT study is designed to confirm the positive findings from the prespecified analysis of the primary outcome in the subgroup of patients with complete methylation from the Phase 2/3 CONNECT study Potential to be the first and only approved treatment for patients with Fragile X syndrome (FXS) (80,000 patients in the U.S. ), and also possess global rights Topline data readout from Phase 3 registrational trial of ZYN002 in FXS (RECONNECT study) in Q3 2025 with potential PDUFA date in 2026 Phase 3 registrational trial in 22q11.2 deletion syndrome (22q) to initiate in 2025 Rare Epilepsy Franchise EPX-100 (clemizole hydrochloride} Most advanced development program in the 5HT2 (serotonin) agonist class Topline data readout from Phase 3 registrational trial in Dravet syndrome (ARGUS Study) anticipated in 2026 Topline data for Phase 3 registrational trial in patients with Lennox-Gastaut syndrome (LIGHTHOUSE study) anticipated in 2026 EPX-200 (lorcaserin hydrochloride) Proven mechanism of action in developmental and epileptic encephalopathies (DEEs) confirmed via non-clinical and clinical data Currently in IND enabling stage Fourth Quarter 2024 Financial Results Net product revenues for the quarter ended December 31, 2024 , were $201.3 million , compared to $168.4 million for the same period in 2023. The 20% growth versus the same period in 2023 is primarily attributed to strong commercial sales of WAKIX driven by continued organic demand tapping into a large market opportunity (approximately 80,000 patients diagnosed with narcolepsy in the U.S. ) and the broad clinical utility of WAKIX across the approximately 9,000 HCPs that we call on (about 5,000 of whom do not participate in an oxybate REMS program). The average number of patients on WAKIX increased by approximately 300 sequentially to approximately 7,100 for the quarter ended December 31, 2024 . GAAP net income for the quarter ended December 31, 2024 , was $49.5 million , or $0.85 earnings per diluted share, compared to GAAP net income of $26.6 million , or $0.45 earnings per diluted share, for the same period in 2023. Non-GAAP adjusted net income was $63.0 million , or $1.08 earnings per diluted share, for the quarter ended December 31, 2024 , compared to Non-GAAP adjusted net income of $42.8 million , or $0.73 per diluted share, for the same period in 2023. Reconciliations of applicable GAAP financial measures to Non-GAAP financial measures are included at the end of this press release. Harmony’s operating expenses included the following: Research and Development expenses were $34.7 million in the fourth quarter of 2024, as compared to $30.3 million for the same quarter in 2023, representing a 14% increase; Sales and Marketing expenses were $27.6 million in the fourth quarter of 2024, as compared to $26.9 million for the same quarter in 2023, representing a 3% increase; General and Administrative expenses were $28.9 million in the fourth quarter of 2024, as compared to $27.9 million for the same quarter in 2023, representing a 4% increase; and Total Operating Expenses were $91.1 million in the fourth quarter of 2024, as compared to $85.1 million for the same quarter in 2023, representing a 7% increase. Full Year 2024 Financial Results Net product revenues for the year ended December 31, 2024 , were $714.7 million , compared to $582.0 million for the same period in 2023. The 23% growth versus the same period in 2023 is primarily attributed to strong commercial sales of WAKIX driven by continued organic demand tapping into a large market opportunity (approximately 80,000 patients diagnosed with narcolepsy in the U.S. ) and the broad clinical utility of WAKIX across the approximately 9,000 HCPs that we call on (about 5,000 of whom do not participate in an oxybate REMS program). GAAP net income for the year ended December 31, 2024 , was $145.5 million , or $2.51 earnings per diluted share, compared to GAAP net income of $128.9 million , or $2.13 earnings per diluted share, for the same period in 2023. Non-GAAP adjusted net income was $233.9 million , or $4.04 earnings per diluted share, for the year ended December 31, 2024 , compared to Non-GAAP adjusted net income of $188.4 million , or $3.12 per diluted share, for the same period in 2023. Reconciliations of applicable GAAP financial measures to Non-GAAP financial measures are included at the end of this press release. Harmony’s operating expenses included the following: Research and Development expenses were $145.8 million for the year ended December 31, 2024 , as compared to $76.1 million for the prior year, representing an 92% increase, primarily driven by a $25.5 million upfront licensing fee as part of the 2024 Bioprojet Sublicense Agreement for BP1.15205, an orexin-2 receptor agonist, and a $17.1 million IPR&D charge related to the acquisition of Epygenix Sales and Marketing expenses were $110.9 million for the year ended December 31, 2024 , as compared to $97.4 million for the prior year, representing a 14% increase; General and Administrative expenses were $110.4 million for the year ended December 31, 2024 , as compared to $95.3 million for the prior year, representing a 16% increase; and Total Operating Expenses were $367.1 million for the year ended December 31, 2024 , as compared to $268.8 million for the prior year, representing a 37% increase. As of December 31, 2024 , Harmony had cash, cash equivalents and investments of $576.1 million , compared to $425.6 million as of December 31, 2023 . 2025 Net Product Revenue Guidance Expect full year 2025 net product revenue of $820 million to $860 million . Share Repurchase Program The remaining amount of common stock authorized for repurchases as of December 31, 2024 , was $150 million . Conference Call Today at 8:30 a.m. ET We are hosting our fourth quarter and full year 2024 financial results conference call and webcast today, beginning at 8:30 a.m. Eastern Time . The live and replay webcast of the call will be available on the investor relations page of our website at https://ir.harmonybiosciences.com/. To participate in the live call by phone, dial 800-445-7795 (domestic) or 785-424-1699 (international), and reference passcode HRMYQ424. Non-GAAP Financial Measures In addition to our GAAP results, we present certain Non-GAAP metrics including Non-GAAP adjusted net income and Non-GAAP adjusted net income per share, which we believe provides important supplemental information to management and investors regarding our performance. These measurements are not a substitute for GAAP measurements, and the manner in which we calculate Non-GAAP adjusted net income and Non-GAAP adjusted net income per share may not be identical to the manner in which other companies calculate adjusted net income and adjusted net income per share. We use these Non-GAAP measurements as an aid in monitoring our financial performance from quarter-to-quarter and year-to-year and for benchmarking against comparable companies. Non-GAAP financial measures should not be considered in isolation or as a substitute for comparable GAAP measures; should be read in conjunction with our consolidated financial statements prepared in accordance with GAAP; have no standardized meaning prescribed by GAAP; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future there may be other items that we may exclude for purposes of our Non-GAAP financial measures; and we may in the future cease to exclude items that we have historically excluded for purposes of our Non-GAAP financial measures. About WAKIX® (pitolisant) Tablets WAKIX, a first-in-class medication, is approved by the U.S. Food and Drug Administration for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of EDS in pediatric patients 6 years of age and older with narcolepsy. It was granted orphan drug designation for the treatment of narcolepsy in 2010, and breakthrough therapy designation for the treatment of cataplexy in 2018. WAKIX is a selective histamine 3 (H₃) receptor antagonist/inverse agonist. The mechanism of action of WAKIX is unclear; however, its efficacy could be mediated through its activity at H₃ receptors, thereby increasing the synthesis and release of histamine, a wake promoting neurotransmitter. WAKIX was designed and developed by Bioprojet ( France ). Harmony has an exclusive license from Bioprojet to develop, manufacture and commercialize pitolisant in the United States . Indications and Usage WAKIX is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of excessive daytime sleepiness (EDS) in pediatric patients 6 years of age and older with narcolepsy. Important Safety Information Contraindications WAKIX is contraindicated in patients with known hypersensitivity to pitolisant or any component of the formulation. Anaphylaxis has been reported. WAKIX is also contraindicated in patients with severe hepatic impairment. Warnings and Precautions WAKIX prolongs the QT interval; avoid use of WAKIX in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval. Avoid use in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval. The risk of QT prolongation may be greater in patients with hepatic or renal impairment due to higher concentrations of pitolisant; monitor these patients for increased QTc. Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment. WAKIX is contraindicated in patients with severe hepatic impairment and not recommended in patients with end-stage renal disease (ESRD). Adverse Reactions In the placebo-controlled clinical trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and at least twice placebo) for WAKIX were insomnia (6%), nausea (6%), and anxiety (5%). Other adverse reactions that occurred at ≥2% and more frequently than in patients treated with placebo included headache, upper respiratory tract infection, musculoskeletal pain, heart rate increased, hallucinations, irritability, abdominal pain, sleep disturbance, decreased appetite, cataplexy, dry mouth, and rash. In the placebo-controlled phase of the clinical trial conducted in pediatric patients 6 years and older with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and greater than placebo) for WAKIX were headache (19%) and insomnia (7%). The overall adverse reaction profile of WAKIX in the pediatric clinical trial was similar to that seen in the adult clinical trial program. Drug Interactions Concomitant administration of WAKIX with strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold. Reduce the dose of WAKIX by half. Concomitant use of WAKIX with strong CYP3A4 inducers decreases exposure of pitolisant by 50%. Dosage adjustments may be required. H1 receptor antagonists that cross the blood-brain barrier may reduce the effectiveness of WAKIX. Patients should avoid centrally acting H1 receptor antagonists. WAKIX is a borderline/weak inducer of CYP3A4. WAKIX may reduce the effectiveness of sensitive CYP3A4 substrates, including hormonal contraceptives. Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with WAKIX and for at least 21 days after discontinuing treatment. Use in Specific Populations There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to WAKIX during pregnancy. Patients should be encouraged to enroll in the WAKIX pregnancy registry if they become pregnant. To enroll or obtain information from the registry, patients can call 1-800-833-7460. The safety and effectiveness of WAKIX have not been established for treatment of excessive daytime sleepiness in pediatric patients less than 6 years of age with narcolepsy. The safety and effectiveness of WAKIX have not been established for treatment of cataplexy in pediatric patients with narcolepsy. WAKIX is extensively metabolized by the liver. WAKIX is contraindicated in patients with severe hepatic impairment. Dosage adjustment is required in patients with moderate hepatic impairment. WAKIX is not recommended in patients with end-stage renal disease. Dosage adjustment of WAKIX is recommended in patients with eGFR <60 mL/minute/1.73 m2. Dosage reduction is recommended in patients known to be poor CYP2D6 metabolizers; these patients have higher concentrations of WAKIX than normal CYP2D6 metabolizers. Please see the Full Prescribing Information for WAKIX for more information. To report suspected adverse reactions, contact Harmony Biosciences at 1-800-833-7460 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. About Narcolepsy Narcolepsy is a rare, chronic, debilitating neurological disease of sleep-wake state instability that impacts approximately 170,000 Americans and is primarily characterized by excessive daytime sleepiness (EDS) and cataplexy – its two cardinal symptoms – along with other manifestations of REM sleep dysregulation (hallucinations and sleep paralysis), which intrude into wakefulness. EDS is the inability to stay awake and alert during the day and is the symptom that is present in all people living with narcolepsy. In most patients, narcolepsy is caused by the loss of hypocretin/orexin, a neuropeptide in the brain that supports sleep-wake state stability. This disease affects men and women equally, with typical symptom onset in adolescence or young adulthood; however, it can take up to a decade to be properly diagnosed. About Idiopathic Hypersomnia Idiopathic Hypersomnia (IH) is a rare and chronic neurological disease that is characterized by excessive daytime sleepiness (EDS) despite sufficient or even long sleep time. EDS in IH cannot be alleviated by naps, longer sleep or more efficient sleep. People living with IH experience significant EDS along with the symptoms of sleep inertia (prolonged difficulty waking up from sleep) and 'brain fog' (impaired cognition, attention, and alertness). The cause of IH is unknown, but it is likely due to alterations in areas of the brain that stabilize states of sleep and wakefulness. IH is one of the central disorders of hypersomnolence and, like narcolepsy, is a debilitating sleep disorder that can result in significant disruption in daily functioning. About ZYN002 ZYN002 is the first-and-only pharmaceutically manufactured synthetic cannabidiol devoid of THC and formulated as a patent-protected permeation-enhanced gel for transdermal delivery through the skin and into the circulatory system. The product is manufactured through a synthetic process in a cGMP facility and is not extracted from the cannabis plant. ZYN002 does not contain THC, the compound that causes the euphoric effect of cannabis, and has the potential to be a nonscheduled product if approved. Cannabidiol, the active ingredient in ZYN002, has been granted orphan drug designation by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of FXS and for the treatment of 22q. Additionally, ZYN002 has received FDA Fast Track designation for the treatment of behavioral symptoms in patients with FXS. About Fragile X Syndrome Fragile X syndrome (FXS) is a rare genetic disorder that is the leading known cause of both inherited intellectual disability and autism spectrum disorder. The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. While the exact prevalence is unknown, upwards of 80,000 patients in the U.S. and 121,000 patients in the European Union and the UK are believed to have FXS, based on FXS prevalence estimates of approximately 1 in 4,000 to 7,000 in males and approximately 1 in 8,000 to 11,000 in females. There is a significant unmet medical need in patients living with FXS as there are currently no FDA-approved treatments for this disorder. FXS is caused by a mutation in FMR1, a gene which modulates a number of systems, including the endocannabinoid system, and most critically, codes for a protein called FMRP. The FMR1 mutation manifests as multiple repeats of a DNA segment, known as the CGG triplet repeat, resulting in deficiency or lack of FMRP. FMRP helps regulate the production of other proteins and plays a role in the development of synapses, which are critical for relaying nerve impulses, and in regulating synaptic plasticity. In people with full mutation of the FMR1 gene, the CGG segment is repeated more than 200 times, and in most cases causes the gene to not function. Methylation of the FMR1 gene also plays a role in determining functionality of the gene. In approximately 60% of patients with FXS, who have complete methylation of the FMR1 gene, no FMRP is produced, resulting in dysregulation of the systems modulated by FMRP. About Clemizole Hydrochloride (EPX-100) EPX-100, clemizole hydrochloride, is under development for the treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). EPX-100 acts by targeting central 5-hydroxytryptamine receptors to modulate serotonin signaling. The drug candidate is administered orally twice a day in a liquid formulation and has been developed based on a proprietary phenotype-based zebrafish drug screening platform. DS is caused by a loss of function mutation in the SCN1A gene, and scn1 mutant zebrafish replicate the genetic etiology and phenotype observed in the majority of DS patients. The scn1Lab mutant zebrafish model that expresses voltage gated sodium channels has been used for high-throughput screening of compounds that modulate Nav1.1 in the central nervous system. About Dravet Syndrome Dravet syndrome (DS) is a severe and progressive epileptic encephalopathy that begins in infancy and causes significant impact on patient functioning. DS begins in the first year of life and is characterized by high seizure frequency and severity, intellectual disability, and a risk of sudden unexpected death in epilepsy. Approximately 85% of Dravet syndrome cases are caused by de novo loss-of-function (LOF) mutations in a voltage-gated sodium channel gene, SCN1A1. DS has an estimated incidence rate of 1:15,700. About Lennox-Gastaut Syndrome Lennox-Gastaut syndrome (LGS) is a rare and drug-resistant epileptic encephalopathy characterized by onset in children between 3-5 years of age. The underlying cause of LGS is unknown and can be related to a wide range of factors including genetic differences and structural differences in the brain. As a result, patients experience multiple seizure types, including atonic seizures, and developmental, cognitive, and behavioral issues. LGS affects approximately 48,000 patients in the U.S. About Harmony Biosciences Harmony Biosciences is a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases who have unmet medical needs. Driven by novel science, visionary thinking, and a commitment to those who feel overlooked, Harmony Biosciences is nurturing a future full of therapeutic possibilities that may enable patients with rare neurological diseases to truly thrive. Established by Paragon Biosciences, LLC , in 2017 and headquartered in Plymouth Meeting, Pa. , we believe that when empathy and innovation meet, a better future can begin; a vision evident in the therapeutic innovations we advance, the culture we cultivate, and the community programs we foster. For more information, please visit www.harmonybiosciences.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding our full year 2024 net product revenue, expectations for the growth and value of WAKIX, plans to submit an sNDA for pitolisant in idiopathic hypersomnia; our future results of operations and financial position, business strategy, products, prospective products, product approvals, the plans and objectives of management for future operations and future results of anticipated products. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our commercialization efforts and strategy for WAKIX; the rate and degree of market acceptance and clinical utility of pitolisant in additional indications, if approved, and any other product candidates we may develop or acquire, if approved; our research and development plans, including our plans to explore the therapeutic potential of pitolisant in additional indications; our ongoing and planned clinical trials; our ability to expand the scope of our license agreements with Bioprojet Société Civile de Recherche (“Bioprojet”); the availability of favorable insurance coverage and reimbursement for WAKIX; the timing of, and our ability to obtain, regulatory approvals for pitolisant for other indications as well as any other product candidates; our estimates regarding expenses, future revenue, capital requirements and additional financing needs; our ability to identify, acquire and integrate additional products or product candidates with significant commercial potential that are consistent with our commercial objectives; our commercialization, marketing and manufacturing capabilities and strategy; significant competition in our industry; our intellectual property position; loss or retirement of key members of management; failure to successfully execute our growth strategy, including any delays in our planned future growth; our failure to maintain effective internal controls; the impact of government laws and regulations; volatility and fluctuations in the price of our common stock; the significant costs and required management time as a result of operating as a public company; the fact that the price of Harmony's common stock may be volatile and fluctuate substantially; statements related to our intended share repurchases and repurchase timeframe and the significant costs and required management time as a result of operating as a public company. These and other important factors discussed under the caption "Risk Factors" in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (the " SEC ") on February 25, 2025 , and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARY CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (LOSS) (In thousands, except share and per share data) Three Months Ended Year Ended December 31 , December 31 , December 31 , December 31 , 2024 2023 2024 2023 Net product revenue $ 201,267 $ 168,412 $ 714,734 $ 582,022 Cost of product sold 54,409 43,152 156,815 121,236 Gross profit 146,858 125,260 557,919 460,786 Operating expenses: Research and development 34,666 30,306 145,825 76,063 Sales and marketing 27,600 26,886 110,916 97,404 General and administrative 28,865 27,872 110,352 95,289 Total operating expenses 91,131 85,064 367,093 268,756 Operating income 55,727 40,196 190,826 192,030 Loss on debt extinguishment — — — (9,766) Other expense (income), net 160 193 (68) 159 Interest expense (4,209) (4,796) (17,496) (23,757) Interest income 4,477 4,096 18,542 14,730 Income before income taxes 56,155 39,689 191,804 173,396 Income tax benefit (expense) (6,680) (13,082) (46,311) (44,543) Net income $ 49,475 $ 26,607 $ 145,493 $ 128,853 EARNINGS PER SHARE: Basic $ 0.87 $ 0.46 $ 2.56 $ 2.17 Diluted $ 0.85 $ 0.45 $ 2.51 $ 2.13 Weighted average number of shares of common stock - basic 57,097,092 58,320,400 56,885,455 59,469,648 Weighted average number of shares of common stock - diluted 58,218,052 58,853,292 57,869,915 60,372,397 HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARIES CONSOLIDATED BALANCE SHEETS (In thousands, except share and per share data) December 31 , December 31 , 2024 2023 ASSETS CURRENT ASSETS: Cash and cash equivalents $ 453,001 $ 311,660 Investments, short-term 14,185 41,800 Trade receivables, net 83,033 74,140 Inventory, net 7,198 5,363 Prepaid expenses 13,714 12,570 Other current assets 8,121 5,537 Total current assets 579,252 451,070 NONCURRENT ASSETS: Property and equipment, net 1,257 371 Restricted cash 270 270 Investments, long-term 108,874 72,169 Intangible assets, net 113,263 137,108 Deferred tax asset 190,398 144,162 Other noncurrent assets 5,886 6,298 Total noncurrent assets 419,948 360,378 TOTAL ASSETS $ 999,200 $ 811,448 LIABILITIES AND STOCKHOLDERS’ EQUITY CURRENT LIABILITIES: Trade payables $ 13,744 $ 17,730 Accrued compensation 18,776 23,747 Accrued expenses 120,640 99,494 Current portion of long-term debt 16,250 15,000 Other current liabilities 5,672 7,810 Total current liabilities 175,082 163,781 NONCURRENT LIABILITIES: Long-term debt, net 163,016 178,566 Other noncurrent liabilities 1,947 2,109 Total noncurrent liabilities 164,963 180,675 TOTAL LIABILITIES 340,045 344,456 COMMITMENTS AND CONTINGENCIES (Note 13) STOCKHOLDERS’ EQUITY: Common stock—$0.00001 par value; 500,000,000 shares authorized at December 31, 2024 and December 31, 2023 , respectively; 57,144,887 and 56,769,081 shares issued and outstanding at December 31, 2024 and December 31, 2023 , respectively 1 1 Additional paid in capital 656,872 610,266 Accumulated other comprehensive (loss) income 66 2 Retained earnings (accumulated deficit) 2,216 (143,277) TOTAL STOCKHOLDERS’ EQUITY 659,155 466,992 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $ 999,200 $ 811,448 HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARIES RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL RESULTS (In thousands except share and per share data) Three Months Ended Year Ended December 31 , December 31 , December 31 , December 31 , 2024 2023 2024 2023 GAAP net income $ 49,475 $ 26,607 $ 145,493 $ 128,853 Non-GAAP Adjustments: Non-cash interest expense (1) 169 185 700 3,246 Depreciation 6 164 267 514 Amortization (2) 5,962 5,961 23,845 23,845 Stock-based compensation expense 9,856 8,894 42,701 31,205 Licensing fee and milestone payments (3) - - 26,500 750 Loss on debt extinguishment (4) - - - 9,766 Transaction related costs (5) - 9,804 17,095 9,804 Income tax effect related to non-GAAP adjustments (6) (2,442) (8,789) (22,657) (19,624) Non-GAAP adjusted net income $ 63,026 $ 42,826 $ 233,944 $ 188,359 GAAP reported net income per diluted share $ 0.85 $ 0.45 $ 2.51 $ 2.13 Non-GAAP adjusted net income per diluted share $ 1.08 $ 0.73 $ 4.04 $ 3.12 Weighted average number of shares of common stock used in non-GAAP diluted per share 58,218,052 58,853,292 57,869,915 60,372,397 (1) Includes amortization of deferred finance charges. (2) Includes amortization of intangible asset related to WAKIX. (3) Amount represents upfront licensing fee incurred upon closing the 2024 Bioprojet Sublicense Agreement, milestone payment related to HBS-102 in September 2024 and milestone payment related to HBS-102 in March 2023 . (4) Includes loss on extinguishment of the Blackstone Credit Agreement. (5) Includes IPR&D charge related to the acquisitions of Epygenix in April 2024 and Zynerba in October 2023 . (6) Calculated using the reported effective tax rate for the periods presented less impact of discrete items. View source version on businesswire.com: https://www.businesswire.com/news/home/20250225347698/en/ Harmony Biosciences Investor: Brennan Doyle 484-539-9700 bdoyle@harmonybiosciences.com Harmony Biosciences Media: Cate McCanless 202-641-6086 cmccanless@harmonybiosciences.com Source: Harmony Biosciences Holdings, Inc.