Cav2.1

Orum’s new program in immuno-oncology achieves simultaneous blockade of PD-1/PD-L1 pathway and delivery of a Cbl-b inhibitor using anti-PD-1-Cbl-bi conjugates and demonstrates enhanced T cell activation in vitro compared to anti-PD-1 alone, even in the presence of immunosuppressive factors ORM-6151 shows superior tolerability and robust single-dose efficacy, both in vitro and in vivo compared to CC-90009 or Mylotarg™, suggesting the potential for an improved therapeutic option in AML that appropriately balances efficacy with safety and tolerability of a clinically validated GSPT1 degradation mechanism Orum has identified pharmacodynamic biomarkers as predictors of efficacy to support clinical development of ORM-5029 in HER2-expressing solid tumors BOSTON & DAEJEON, South Korea--(BUSINESS WIRE)-- Orum Therapeutics, a clinical-stage private biotechnology company pioneering cell-specific targeted protein degradation (TPD² ™) and targeted protein stabilization (TPS² ™), today announced new preclinical data for three of Orum’s therapeutic programs: ORM-5029, which is a proprietary GSPT1 degrader conjugated to HER2-targeting antibody pertuzumab; ORM-6151, which delivers GSPT1 degrader to CD33+ tumors; and its new immuno-oncology program for a Cbl-b inhibitor (Cbl-bi) conjugated to anti-PD-1 antibody pembrolizumab. The data were presented in three posters at the 2023 American Association for Cancer Research (AACR) Annual Meeting. “We are pleased to present new data supporting clinical development of two programs from our TPD² GSPT1 Degrader Platform, which was developed to improve the therapeutic window and realize the full potential of GSPT1 degraders through precision delivery to cancer cells via antibody drug conjugates,” said Peter Park, Ph.D., Chief Scientific Officer of Orum Therapeutics. “We are also excited to unveil at AACR our new TPS² platform, which has the potential to achieve the full promise of Cbl-b inhibitors through T cell-specific delivery. With this novel approach, we show that we can limit unwanted systemic exposure, including the risk of toxicity associated with c-Cbl inhibition, prolong the activation of exhausted PD-1+ T cells, and provide resistance to negative environmental cues such as TGF-β or regulatory T cells. We believe our approach of harnessing the power of protein degraders and stabilizers with the precision of antibody targeting will improve the treatment of cancer for more patients.” Details of the data presented are as follows: Title: A novel antibody-enabled Dual-precision Targeted Protein Stabilization (TPS²) that augments anti-tumor immune response by targeting Cbl-b inhibitor to exhausted T cells while blocking checkpoint molecule, PD-1 Presenter: Joanne Lim, Ph.D. Abstract Number: 4436 Summary: Cbl-b inhibition results in stabilization of intracellular proteins downstream of the T cell activation pathways. Using a murine model well-established to be refractory to anti-PD-1 antibody treatment, we demonstrated that anti-PD-1-Cbl-b inhibitor approach increased effector T cell markers in the tumor and delayed tumor growth. Presented Data: The delivery of Cbl-b inhibitor (Cbl-bi) conjugated to anti-PD-1 antibody enhances the saturating, maximum activation of anti-PD-1 antibody by 300% in PD-1/PD-L1 blockade assay. Anti-PD-1-Cbl-bi conjugates enhance T cell responses of mixed lymphocyte reaction in a dose-dependent manner and overcome suppressive effects of TGF-β and Treg cells compared to antibody alone in vitro. Anti-PD-1-Cbl-bi conjugates enhance ex vivo activation of tumor-associated T cells from human cancer patients compared to antibody alone or when treated with antibody and unconjugated Cbl-bi. Anti-PD-1-Cbl-bi conjugates delay the growth of melanoma tumors in hPD-1 transgenic mice, with corresponding increase in intratumoral transcript levels of CD3e, granzyme B, and perforin in the tumor. Title: ORM-6151: A first-in-class CD33-antibody enabled GSPT1 degrader for AML Presenter: James Palacino, Ph.D. Abstract Number: 2700 Summary: ORM-6151 shows robust single-dose efficacy, both in vitro and in vivo with superiority or comparability to standard of care (SOC) agents. In addition, in vitro testing demonstrated superior tolerability to healthy bone marrow progenitor cells, suggesting better tolerability. Responses in representative TP53 wild-type and mutant AML models demonstrated comparable activity, indicating the potential for responses in a large percentage of AML patients with poor treatment options. Presented Data: ORM-6151 shows robust in vitro activity in p53 wild-type and mutant cell models. In ex-vivo AML blasts, ORM-6151 demonstrates efficacy superior to CC-90009, a small-molecule GSPT1 degrader, or Mylotarg, an FDA-approved treatment for AML. Compared to CC-90009 or Mylotarg, ORM-6151 exhibits minimal cytotoxic activity to healthy hematopoietic progenitor cells in vitro. A single treatment of ORM-6151 at 3 mg/kg regresses MV4-11 tumors in vivo mouse model with 9/9 complete response (CR), and a single dose of 1 mg/kg produced equivalent antitumor effect as SOC doublet given at optimal repeated dose. Title: Development of RNAscope multiplex-based assay for exploratory pharmacodynamic biomarkers assessment in breast cancer patients from Phase I clinical trial of ORM-5029, a potent GSPT1 degrader Presenter: Shikha Saini, Ph.D. Abstract Number: 2118 Summary: To fulfill the need to develop pharmacodynamic biomarkers as predictors of efficacy to support clinical development of ORM-5029, Orum identified a novel GSPT1 antibody for detection of depletion following treatment with ORM-5029. GSPT1 depletion and subsequent activation of the integrated stress response are both seen following in vitro or in vivo treatment with ORM-5029. Degree of pharmacodynamic (PD) change correlates with depth and duration of in vivo response. Orum is currently developing a multiplexed (IF/ISH/ISH) assay to track PD responses in patients, with an aim to better predict responses and efficacious doses. Presented Data: Orum identified the depletion of GSPT1 as a target-proximal pharmacodynamic biomarker in ORM-5029 treated in vitro and in vivo samples. Loss of GSPT1 drives activation of integrated stress response and upregulation of ATF3 and DDIT3 mRNA and these responses are also seen following treatment with ORM-5029, in both in vitro BT-474 cells and in vivo HCC1568 mouse model. PD responses correlate with degree and duration of response in an in vivo model treated with ORM-5029. The posters are available to download through the links below: PD-1-Cbl-bi TPS² preclinical poster: ORM-6151 preclinical poster: ORM-5029 predictive biomarker poster: About Orum’s TPS² Approach Orum’s Dual-precision Targeted Protein Stabilization (TPS²) approach combines novel payloads with the precise cell delivery mechanism of antibodies to increase the levels of intracellular target proteins in a cell-type-specific manner for oncology and immuno-oncology. The first program applying the TPS² approach is a Cbl-b inhibitor (Cbl-bi) conjugated to anti-PD-1 antibody. By delivering Cbl-bi specifically to exhausted T cells, the conjugate is designed to restore effector T cell function, where PD-1 checkpoint blockade alone is insufficient, while also enabling T cells to overcome the immunosuppressive mechanisms in a tumor microenvironment. About Orum’s GSPT1 Platform Using the TPD² Approach Orum’s GSPT1 platform uses the company’s unique Dual-precision Targeted Protein Degradation (TPD²) approach to build novel targeted protein degraders combined with the precise tumor cell delivery mechanisms of antibodies to generate innovative, first-in-class, cell-specific TPDs for the treatment of cancer. Orum has developed new molecular glue degrader payloads to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, the payloads are designed to be delivered specifically to cancer cells and degrade the intracellular target protein GSPT1 and cause tumor cell death. About Orum Therapeutics Orum Therapeutics is a private, clinical-stage biotech pioneering the development of tumor-directed targeted protein degraders (TPD²) and stabilizers (TPS²) with the precision of antibody targeting to improve cancer treatment for more patients. The first therapeutic candidates from the TPD² GSPT1 platform, ORM-5029 and ORM-6151, are in clinical development for the treatment of solid tumors and hematologic cancers, respectively. The first program applying the TPS² approach is a Cbl-b inhibitor conjugated to anti-PD-1 antibody. Orum is located in Boston, US, and Daejeon, South Korea. For more info, visit . Forward-Looking Statements This press release contains forward-looking statements that are based on the current expectations and beliefs of Orum Therapeutics, Inc. (“Orum”). Statements in this release regarding matters that are not historical facts, including, but not limited to, statements relating to the potential for clinical efficacy, potency, and tolerability of Orum’s products; the potential for conducting and successfully completing clinical trials, translation of preclinical and non-human data to the clinical and human contexts, obtaining favorable trial results, conducting later-phase trials, obtaining regulatory approval of product candidates for sale, successfully commercializing product candidates, and improving the cancer treatment for more patients; the types of cancer that might be treated by Orum products; the successful prediction of patient responses and efficacious doses; and the preferability of Orum products to others available are forward-looking statements. These forward-looking statements are based on management’s expectations and assumptions as of the date of this release and are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, without limitation, the uncertain and continually changing impacts and expected duration of the COVID-19 pandemic; the uncertainty of success in research and development activities; risks related to clinical trials, including potential delays, safety issues, or negative results; competition from alternative therapies; the risk that Orum may not be able to maintain and enforce its intellectual property; the risk that product candidates may not be successfully commercialized or adopted; the availability of financing; and risks related to the recruitment and retention of key employees, fluctuating markets and economic conditions, health care reform, prices, and reimbursement rates. The forward-looking statements in this presentation speak only as of the date of this release, and Orum undertakes no obligation to update or revise any of the statements. Orum cautions investors not to place considerable reliance on the forward-looking statements contained in this release.

COMBINEDBrain takes steps to break down language barriers perpetuating health inequity in research by translating patient registry informed consent and health surveys into three languagesNASHVILLE, Tenn., Sept. 29, 2022 (GLOBE NEWSWIRE) -- COMBINEDBrain (Consortium for Outcome Measures and Biomarkers for Neurodevelopmental Disorders), a non-profit organization of patient advocacy groups representing rare genetic neurodevelopmental disorders, is pleased to announce they have been awarded a Global Genes Health Equity RARE Patient Impact Grant which will be used to translate the ClinGen Health Surveys into French, German, and Italian, in addition to Spanish and English which are currently available. These additional languages will allow more rare disease patients from around the world to participate in research. This spring, as members of COMBINEDBrain met to plan the launch of natural history studies, it became apparent that language was a major barrier to recruiting patients from all parts of the world. Without exception, these groups found that offering English-only study documents delayed community engagement and enrollment. Many families of people with rare diseases express strong interest in sharing their experiences. Patients and caregivers understand the importance of natural history research in improving understanding of rare and ultra-rare diseases. Many organizations in COMBINEDBrain are working with Across Healthcare’s Matrix to collect patient-centered data. Matrix has platform menus and navigation tools available in Spanish, French, German, and Italian. However, the consent forms and surveys were not available in multiple languages. Many families for whom English is not their first language expressed difficulty understanding the informed consent and the health survey questions. “For individuals and families facing a rare disease, the journey is already incredibly difficult,” said Craig Martin, CEO of Global Genes. “For those in historically underserved or marginalized communities, the struggle is often even more challenging. Through our Impact grants, we are pleased to support leaders on a global scale with resources to more effectively collect, create and share information and to help lessen burdens and improve experiences and outcomes for underrepresented members of the rare disease community.” The Global Genes health equity grant will help to break down this language barrier and improve health equity in research and treatment of rare neurodevelopmental disorders. The ClinGen surveys are a National Institutes of Health (NIH) funded resource designed to collect consistent health histories for use in precision medicine and research. The grant will fund medical-grade translation of these respected surveys by LanguageLink into languages other than English. COMBINEDBrain plans to share the translations back to the ClinGen Project for dissemination around the world. Breaking down language barriers is necessary in order to include the experience of diverse populations in health research. Increasing diversity leads to improved research, diagnosis, standards of care, and a more comprehensive and inclusive understanding of disease and the patient journey. “COMBINEDBrain represents neurodevelopmental disorders, but the impact of these translations will go far beyond our scope, to help increase diversity in research on genetic disorders around the world. I am so proud of the leaders of our member groups, who had the vision to be inclusive and collaborative, and so grateful to Global Genes for incentivizing this work.” “Within rare disease populations, there is a dire need to be as inclusive as possible by breaking down any barriers. In the past, a huge barrier has been providing data collection platforms only in English. Our Matrix rare disease platform was architected to have multilingual support at its core,” states Jason Colquitt, CEO of Across Healthcare. "This grant is exciting and promising since it will allow us to unlock the ClinGen surveys for French, German, and Italian speaking patients and caregivers who would have previously never been able to participate without these translations. This is a huge win for everyone!” COMBINEDBrain non-profit 501c3 organization with a mission to speed the path to clinical treatments for people with severe rare genetic neurodevelopmental disorders: https://combinedbrain.org ASXL Rare Research Foundation CACNA1A Foundation Coalition to Cure CHD2CureSHANK DYRK1A Syndrome International Foundation FamiliesSCN2A Foundation Foundation for Hao-Fountain Syndrome FOXG1 Research Foundation Glut1 Deficiency FoundationGRIN2B FoundationiDefine Foundation (Kleefstra) KIF1A.ORGNR2F1 FoundationSATB2 Gene FoundationSETBP1 SocietySLC6A1 ConnectShwachman-Diamond Syndrome Alliance IncThe Yellow Brick Road Project (HNRNPH2) Kristin Hatcherkristinhatcher@combinedbrain.org

XEN1101 Phase 2b “X-TOLE” Clinical Trial in Adult Focal Epilepsy on Track for Topline Data in Third Quarter of 2021 Conference Call at 4:30 pm ET Today BURNABY, British Columbia, March 01, 2021 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a neurology-focused biopharmaceutical company, today reported financial results for the year ended December 31, 2020 and provided a corporate update. Dr. Simon Pimstone, Xenon’s Chief Executive Officer, said, “With two of our most advanced proprietary product candidates – XEN1101 and XEN496 – currently in Phase 2 and Phase 3 clinical trials, as well as a number of earlier stage clinical and non-clinical epilepsy assets in development, we believe Xenon is advancing one of the most robust epilepsy pipelines in the biopharmaceutical industry. Our focus remains on driving towards the topline data readout expected in the third quarter of this year from our Phase 2b ‘X-TOLE’ clinical trial examining the use of XEN1101 in adult focal epilepsy.” Mr. Ian Mortimer, Xenon’s President and Chief Financial Officer added, “We were excited to present new pre-clinical data and provide a clinical overview of our XEN1101 program at the ASENT 2021 meeting last week. These presentations highlighted our belief that XEN1101 has key “ease-of-use” attributes that could meaningfully differentiate XEN1101 from other anti-seizure medications currently used to treat adult focal epilepsy. Additionally, we announced that we intend to support the initiation of a Phase 2 proof-of-concept clinical trial in 2021 with academic collaborators at the Icahn School of Medicine at Mount Sinai examining XEN1101 in major depressive disorder and anhedonia.” Highlights and Anticipated Milestones Proprietary Programs XEN1101 is a differentiated Kv7 potassium channel modulator being developed for the treatment of epilepsy and potentially other neurological disorders. Designed as a randomized, double-blind, placebo-controlled, multicenter study, Xenon’s “X-TOLE” study is an ongoing Phase 2b clinical trial to evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in approximately 300 adult patients with focal epilepsy. The primary endpoint is the median percent change in monthly focal seizure frequency from baseline compared to treatment period of active versus placebo. Xenon anticipates that patient randomization will be completed in the first half of 2021, with topline data anticipated in the third quarter of 2021, dependent upon ongoing patient enrollment rates. At ASENT 2021, the virtual annual meeting of the American Society for Experimental Neurotherapeutics, Xenon presented new pre-clinical data combining XEN1101 with commercially approved anti-seizure medications (ASMs) – including lacosamide, levetiracetam, cenobamate, phenytoin, and valproic acid – showing that combining sub-efficacious doses of XEN1101 and other ASMs provided robust efficacy in animal models. This pre-clinical work suggests that XEN1101 may be well suited for use as a monotherapy or applied in a rational polypharmacy setting to treat seizures. Additional pre-clinical data were presented that support the potential benefit of XEN1101 to treat depression and anhedonia. Xenon expects to support the initiation of a Phase 2 proof-of-concept clinical trial in 2021 with academic collaborators at the Icahn School of Medicine at Mount Sinai examining XEN1101 in major depressive disorder and anhedonia. XEN496, a Kv7 potassium channel modulator, is a proprietary pediatric formulation of the active ingredient ezogabine being developed for the treatment of KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE). Xenon has received Fast Track designation and Orphan Drug Designation for XEN496 for the treatment of seizures associated with KCNQ2-DEE from the U.S. Food and Drug Administration (FDA), as well as orphan medicinal product designation from the European Commission. Xenon has initiated a Phase 3 randomized, double-blind, placebo-controlled, parallel group, multicenter clinical trial, called the “EPIK” study, evaluating the efficacy, safety, and tolerability of XEN496 administered as adjunctive treatment in approximately 40 pediatric patients aged one month to less than 6 years with KCNQ2-DEE. XEN007 (active ingredient flunarizine) is a CNS-acting Cav2.1 and T-type calcium channel modulator that is being studied in treatment-resistant childhood absence epilepsy (CAE) and potentially other neurological disorders. A physician-led, Phase 2 proof-of-concept study is ongoing to examine the potential clinical efficacy, safety, and tolerability of XEN007 as an adjunctive treatment in pediatric patients diagnosed with treatment-resistant CAE. A presentation of promising interim data collected from a small number of patients was presented at the virtual annual meeting of the American Epilepsy Society in December 2020. Given the impact of COVID-19 on recruitment, Xenon continues to work with its collaborator to expand the study to include additional sites and expects that topline results from a larger data set will now be available in the second half of 2021. Xenon expects to make a decision in 2021 regarding the future development of XEN007 in CAE. Partnered Programs Xenon has an ongoing collaboration with Neurocrine Biosciences to develop treatments for epilepsy. Neurocrine Biosciences has an exclusive license to XEN901, now known as NBI-921352, a clinical stage selective Nav1.6 sodium channel inhibitor with potential in SCN8A developmental and epileptic encephalopathy (SCN8A-DEE) and other forms of epilepsy. The FDA has provided feedback on an Investigational New Drug (IND) application submitted by Neurocrine Biosciences in support of a Phase 2 clinical trial in SCN8A-DEE patients. Based on this feedback, Neurocrine Biosciences anticipates initiating a Phase 2 clinical trial in adolescent patients (aged 12 years and older) with SCN8A-DEE in the third quarter of 2021, and the trial protocol will be amended to include younger pediatric patients (aged 2-11 years) with SCN8A-DEE as soon as the FDA has reviewed and approved additional non-clinical information. In parallel, Neurocrine Biosciences is advancing clinical plans to develop NBI-921352 for the treatment of adult focal epilepsy and expects to initiate a Phase 2 clinical trial in 2021. Upon IND or equivalent regulatory acceptance for NBI-921352 in adult focal epilepsy, Xenon is eligible to receive a $10.0 million milestone payment; upon FDA acceptance of a protocol amendment for NBI-921352 in pediatric patients (aged 2-11 years) with SCN8A-DEE, Xenon is eligible to receive a $25.0 million milestone payment, or a $15.0 million milestone payment if the IND acceptance for adult focal epilepsy occurs first. Both milestone payments are in the form of 45% cash and a 55% equity investment in Xenon at a 15% premium to Xenon’s 30-day trailing volume weighted average price at that time. Flexion Therapeutics acquired the global rights to develop and commercialize XEN402, a Nav1.7 inhibitor also known as funapide. Flexion’s FX301 consists of XEN402 formulated for extended release from a thermosensitive hydrogel. The initial development of FX301 is intended to support administration as a peripheral nerve block for control of post-operative pain. In February 2021, the FDA cleared an IND for FX301, resulting in a $1.0 million milestone payment due to Xenon, and Flexion anticipates initiating a Phase 1b proof-of-concept clinical trial of popliteal fossa block with FX301 in patients undergoing bunionectomy in the first half of 2021. Topline results from that trial could potentially be available in late 2021. Pursuant to the terms of the agreement, Xenon is eligible to receive up to an additional $7.0 million in milestone payments through initiation of a Phase 2 clinical trial. Corporate Highlights On February 23, 2021, Dr. Ernesto Aycardi resigned as the Company’s Chief Medical Officer, effective April 23, 2021, to pursue another opportunity leading global development for a pharmaceutical company. Xenon is pleased to announce that it has engaged Dr. Kenneth Sommerville to serve as Interim Chief Medical Officer. Dr. Sommerville is a board-certified neurologist, who has over 20 years of experience in the pharmaceutical industry, including positions at Abbott Pharmaceuticals, GW Pharmaceuticals, Pfizer, Inc., King Pharmaceuticals, UCB, and Schwarz Pharma. He has led Phase 2 and Phase 3 epilepsy trials in the U.S. and made major contributions to multiple successful NDA submissions. He is recognized as a leader in neurology drug development, with a particular focus on anti-epileptic drugs, pain, Parkinson’s disease, and abuse-deterrent opioids. He was Adjunct Assistant Professor of Medicine of the Duke University Medical School until June 2019 and was in the private practice of neurology for 11 years (1980-1991) prior to entering the pharmaceutical industry. Dr. Pimstone commented, “On behalf of the Xenon team, we wish our Chief Medical Officer Dr. Ernesto Aycardi well in his future endeavors as he pursues an opportunity to lead global development for a pharmaceutical company, and we are grateful for his many contributions to our clinical programs. We expect a smooth transition as Ernesto will be staying on with Xenon until late April, by which time we will have concluded patient screening in our XEN1101 X-TOLE study. We are delighted to announce that we have engaged Dr. Kenneth Sommerville to serve as Xenon’s interim Chief Medical Officer. We believe Ken is one of the most experienced epilepsy drug developers in the pharmaceutical industry, with more than 20 years of experience in both orphan and larger market indications. In addition to leading the development of Epidiolex to a successful NDA submission for GW Pharmaceuticals, Ken was highly involved in the clinical development of sodium valproate, tiagabine, and lacosamide.” Dr. Ken Sommerville said, “Xenon’s broad pipeline of epilepsy drugs with novel, differentiated mechanisms has the potential to improve patient outcomes. Based on the encouraging data generated to date, I am looking forward to the important clinical read-out from the X-TOLE study, as well as supporting the advancement of other clinical programs within Xenon’s portfolio.” 2020 Financial Results Cash and cash equivalents and marketable securities as of December 31, 2020 were $177.0 million, compared to $141.4 million as of December 31, 2019. There were 35,012,125 common shares and 1,016,000 Series 1 Preferred Shares, which are convertible into common shares on a one-for-one basis at the option of the holder, subject to certain limitations, outstanding as of December 31, 2020. Based on current assumptions, which include fully supporting the planned clinical development of XEN1101, XEN496 and XEN007, Xenon anticipates having sufficient cash to fund operations into 2023, excluding any revenue generated from existing partnerships or potential new partnering arrangements. For the year ended December 31, 2020, Xenon reported total revenue of $32.2 million, compared to $6.8 million for the same period in 2019. The increase was attributable to the recognition of $26.8 million of deferred revenue as well as $5.4 million for research and development services from the license and collaboration agreement with Neurocrine Biosciences, compared to $2.9 and $0.4 million, respectively, in the comparable period. Revenue for the year ended December 31, 2019 also included $3.5 million in connection with the agreement with Flexion. Research and development expenses for the year ended December 31, 2020 were $50.5 million, compared to $38.8 million for the same period in 2019. The increase of $11.7 million was primarily attributable to increased spending on Xenon’s clinical development product candidates XEN1101 and XEN496, and, to a lesser extent, increased spending on pre-clinical, discovery and other internal programs. This was partially offset by decreased spending on XEN901, now known as NBI-921352, as clinical development costs are borne by Neurocrine Biosciences. General and administrative expenses for the year ended December 31, 2020 were $12.9 million compared to $10.8 million for the same period in 2019. The increase of $2.1 million was primarily attributable to increased stock-based compensation expense, insurance premiums and salaries and benefits, partially offset by a decrease in legal fees for intellectual property protection. Other income for the year ended December 31, 2020 was $2.2 million compared to $1.2 million for the same period in 2019. The increase was primarily attributable to an increase in foreign exchange gains largely from the translation of cash and cash equivalents and marketable securities denominated in Canadian dollars to U.S. dollars. Net loss for the year ended December 31, 2020 was $28.8 million, compared to $41.6 million for the same period in 2019. The change was primarily attributable to revenue recognized in the year pursuant to the license and collaboration agreement with Neurocrine Biosciences, partially offset by higher research and development expenses as compared to the same period in 2019. Conference Call Information Xenon will host a conference call and live audio webcast today at 4:30 pm Eastern Time (1:30 pm Pacific Time) to discuss the year-end results and to provide a corporate update. The webcast will be broadcast live on the Investors section of the Xenon website. To participate in the call, please dial (855) 779-9075, or (631) 485-4866 for international callers, and provide conference ID number 6061326. About Xenon Pharmaceuticals Inc. We are a clinical stage biopharmaceutical company committed to developing innovative therapeutics to improve the lives of patients with neurological disorders. We are advancing a novel product pipeline of neurology therapies to address areas of high unmet medical need, with a focus on epilepsy. For more information, please visit . 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 anticipated impact and timing of the COVID-19 pandemic on our business, research and clinical development plans and timelines and results of operations; the timing of and results from clinical trials and pre-clinical development activities, including those related to XEN496, XEN1101, XEN007, and other proprietary products, and those related to NBI-921352, FX301, and other partnered product candidates; the potential efficacy, safety profile, future development plans, addressable market, regulatory success and commercial potential of XEN496, XEN1101, XEN007 and other proprietary and partnered product candidates; the anticipated timing of IND, or IND-equivalent, submissions and the initiation of future clinical trials for XEN496, XEN1101, XEN007, and other proprietary products, and those related to NBI-921352, FX301, and other partnered candidates; the efficacy of our clinical trial designs; our ability to successfully develop and achieve milestones in the XEN496, XEN1101, XEN007 and other proprietary development programs; the timing and results of our interactions with regulators; the potential to advance certain of our product candidates directly into Phase 2 or later stage clinical trials; anticipated enrollment in our clinical trials and the timing thereof; the expansion of the X-TOLE clinical trial and the anticipated timing of the topline data therefrom; the progress and potential of our other ongoing development programs; the potential receipt of milestone payments and royalties from our collaborators; our expectation of having sufficient cash to fund operations into 2023; and the timing of potential publication or presentation of future clinical data. 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: the impact of the COVID-19 pandemic on our business, research and clinical development plans and timelines and results of operations, including impact on our clinical trial sites, collaborators, and contractors who act for or on our behalf, may be more severe and more prolonged than currently anticipated; clinical trials may not demonstrate safety and efficacy of any of our or our collaborators’ product candidates; 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 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 of clinical trials; regulatory agencies may be delayed in reviewing, commenting on or approving any of our or our collaborators’ clinical development plans as a result of the COVID-19 pandemic, which could further delay development timelines; the impact of competition; the impact of expanded product development and clinical activities on operating expenses; impact of new or changing laws and regulations; adverse conditions in the general domestic and global economic markets; as well as the other risks identified in our filings with the 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. Investor/Media Contact: Jodi Regts Xenon Pharmaceuticals Inc. Phone: 604.484.3353 Email: investors@xenon-pharma.com