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Launch of OLPRUVA® underway Topline results from KP1077 phase 2 study demonstrate clinically meaningful benefits for key IH symptoms Q4 2023 net revenue of $13.2M, and FY 2023 net revenue of $27.5M Conference call scheduled for today, March 28, 2024, at 4:30 p.m. ET CELEBRATION, Fla., March 28, 2024 (GLOBE NEWSWIRE) -- Zevra Therapeutics Inc. (NasdaqGS: ZVRA) (Zevra, or the Company), a rare disease therapeutics company, today provided corporate updates and reported its financial results for the fourth quarter and year ended December 31, 2023. “We made solid progress on our key priorities in 2023,” said Neil F. McFarlane, President and Chief Executive Officer of Zevra. “As we look to 2024, our strategic priorities are clear; first, successfully launch OLPRUVA® and ensure access for patients; second, prepare for the launch of arimoclomol; and third, advance the KP1077 development program in sleep disorders. Mr. McFarlane continued, “We are encouraged by the positive data from our Phase 2 study of KP1077 in patients with idiopathic hypersomnia. KP1077 has been well tolerated while demonstrating early signs of differentiated clinical benefits. These data will help inform our registrational study, which we will discuss with FDA at an end of phase 2 meeting.” Recent Business and Corporate Highlights: Completion of the Acquisition of Acer Therapeutics, Inc. (Acer): On November 20, 2023, the Company announced the completion of its acquisition of Acer. The acquisition brought multiple complementary rare disease assets, increased Zevra’s revenue potential, and bolstered Zevra’s commercial and development capabilities. OLPRUVA, an FDA-approved treatment indicated for certain urea cycle disorders (UCDs): To support the commercial launch, the Company accelerated the build-out of a focused and effective customer-facing team with decades of experience in rare diseases. The team includes Rare Disease Sales Specialists, Marketers, Patient Services and Market Access professionals, as well as Medical Science Liaisons and Patient Advocates who are in the field engaging with key customers, with our efforts largely focused on approximately 40 centers of excellence across the United States. To raise awareness of the benefits of OLPRUVA, the Company has established Quick Start, which is a 30-day free trial to allow patients and physicians to gain experience with the treatment. Zevra continues to partner with the patient community and UCD treatment centers of excellence to drive brand recognition, while also working with payors to ensure access to OLPRUVA. The Company has seen a meaningful increase in reimbursement coverage since the acquisition, and currently there is more than 70% overall coverage for OLPRUVA with commercial and government payors. The Company expects that OLPRUVA’s commercial operations and capabilities will provide scale and cost synergies to support and accelerate the launch and commercialization of arimoclomol, if approved. Arimoclomol, an investigational therapeutic candidate for the treatment of Niemann-Pick disease type C (NPC), an ultra-rare, genetic, progressive and fatal neurological disease: During Q4 2023, the Company submitted a comprehensive data set to the U.S. Food and Drug Administration (FDA) supporting its resubmission of the New Drug Application (NDA) for arimoclomol. On March 4, 2024, the Company announced that the FDA had extended the review period for the NDA, resulting in a revised Prescription Drug User Fee Act (PDUFA) date of September 21, 2024. The FDA re-affirmed its intent to present the resubmission for discussion at an advisory committee meeting to be scheduled. If approved, arimoclomol will be a first-in-class, orally delivered treatment for NPC, and the Company will be eligible to receive a Priority Review Voucher. Zevra is preparing for the commercial launch of arimoclomol in the U.S., if approved, and will leverage the commercial infrastructure that is in place for OLPRUVA. The Company plans to publish real-world evidence data from its Expanded Access Program (EAP) and additional data from clinical studies regarding safety and efficacy, to inform physician treatment decision-making and support market access. The Company intends to complete the regulatory filing for arimoclomol in the U.S., and then continue its evaluation of optimal regulatory pathways to approval in the E.U. and other parts of the world. KP1077 (serdexmethylphenidate, or SDX), an investigational therapeutic candidate both for the treatment of idiopathic hypersomnia (IH), a rare sleep disorder characterized by excessive daytime sleepiness, and for the treatment of narcolepsy: On March 26, 2024, the Company reported positive topline data from its placebo-controlled, double-blind, proof-of-concept Phase 2 study of KP1077 in patients with IH. KP1077 was well-tolerated at all dose levels evaluated in the trial, including the highest dose of 320 mg daily, regardless of dosing regimen (once or twice daily), supporting the study’s primary endpoint of safety and tolerability. KP1077 produced clinically meaningful improvement in excessive daytime sleepiness, as assessed by change from baseline in the Epworth Sleepiness Scale. This improvement was maintained during both the five-week open-label titration period and throughout the 2-week double-blind withdrawal period for both dosing regimens. Patients administered KP1077 showed benefits in change from baseline for the IH Severity Scale, Sleep Inertia Visual Analog Scale and Brain Fog severity Scale at the end of the open-label dose titration, and at the end of the double-blind withdrawal period. The study successfully fulfilled the objectives of providing key information for the design of a potentially pivotal efficacy trial, and the results of the secondary efficacy endpoints are supportive of initiating a Phase 3 trial of KP1077. The Company plans to request an end-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration to seek guidance on the Phase 3 clinical trial design. The Company will present new data from a Phase 1 study completed under the narcolepsy IND, and the final results from its Phase 2 study of KP1077 in IH at the upcoming SLEEP 2024 conference. Overview of Q4 2023 and FY 2023 Financial Results: Net revenue for Q4 2023 was $13.2 million, compared to prior year Q4 net revenue of $2.2 million. The components of revenue during the current quarter include ongoing royalties from AZSTARYS®, reimbursements from the French EAP for arimoclomol, and some initial sales of OLPRUVA. Research and development (R&D) expenses were $11.4 million for Q4 2023, compared to $6.5 million in Q4 2022. The increase in R&D expenses was primarily driven by the ongoing Phase 2 clinical study in KP1077, and ongoing work supporting to support the arimoclomol NDA which was resubmitted to the FDA in December 2023. General and administrative (G&A) expenses were $14.7 million for Q4 2023, compared to $4.7 million in Q4 2022. The period-over-period increase was primarily related to an increase in personnel costs and professional fees associated with our commercial and business development activities. Net loss for Q4 2023 was ($19.6) million, or ($0.51) per basic and diluted share, compared to a net loss of ($3.0) million, or ($0.09) per basic and diluted share for the same period in 2022. Net revenue for FY 2023 was $27.5 million compared to prior year net revenue of $10.2 million. The period-over-period increase was primarily attributed to an increase of $18.5 in royalties and milestones received under the AZSTARYS License Agreement, which includes $15.0 million in one-time net sales milestone payments earned during FY 2023, an increase in sales of arimoclomol of $3.3 million, partially offset by a decrease in consulting revenue of $4.5 million. R&D expenses were $39.8 million for FY 2023, compared to $19.8 million for FY 2022. The increase in R&D expenses was primarily driven by the ongoing KP1077 Phase 2 clinical study in IH, along with work to prepare the arimoclomol NDA for resubmission. G&A expenses were $34.3 million for FY 2023, compared to $15.0 million in FY 2022. The period-over-period increase was primarily related to an increase in personnel costs and professional fees associated with our commercial and business development activities. Net loss for FY 2023 was ($46.0) million, or ($1.30) per basic and diluted share, which includes the non-cash impact of the change in fair value adjustment for the warrant liability of ($1.4) million, or ($0.04) per basic and diluted share. Net loss for FY 2022 was ($26.8) million, or ($0.78) per basic and diluted share. As of December 31, 2023, total cash, cash equivalents, and cash investments were $67.7 million, a decrease of $15.7 million compared to $83.4 million as of September 30, 2023. The decrease was driven, in part, by increased third-party R&D costs related to the KP1077 clinical development program, the arimoclomol program, and increased G&A expenses during the period as the Company invested in its commercial infrastructure. Based on our current operating forecast and available resources, our cash runway is expected to extend into 2026. Our cash runway forecast includes revenue from the expected sales of OLPRUVA, ongoing reimbursements from the French EAP for arimoclomol, and investments into the incremental commercial activities needed to support the launch of arimoclomol, if approved, and completion of the KP1077 development program for IH. Our cash runway forecast does not include any commercial revenue from arimoclomol which could follow a potential FDA approval, or the potential sale of the Priority Review Voucher which would be received upon approval. On November 17, 2023, Zevra completed the acquisition of Acer. Pursuant to the Merger Agreement, Acer continues as a wholly owned subsidiary of Zevra. The Merger included the acquisition of OLPRUVA® (sodium phenylbutyrate) for oral suspension, which was approved by the FDA on December 27, 2022, for the treatment of urea cycle disorders. Acer also has a pipeline of investigational product candidates, including celiprolol for the treatment of vascular Ehlers-Danlos syndrome, patients with a confirmed type III collagen (COL3A1) mutation. At the effective time of the Merger (the "Effective Time"), each share of common stock of Acer, par value $0.0001 per share, issued and outstanding immediately prior to the Effective Time (excluding cancelled shares and any shares held by holders who have exercised their appraisal rights) were converted into the right to receive (i) 0.1210 fully paid and non-assessable shares of common stock of Zevra, par value $0.0001 per share, and (ii) one non-transferable contingent value right (“CVR”) issued by Zevra, which represents the right to receive one or more contingent payments up to an additional $76.0 million upon the achievement, if any, of certain commercial and regulatory milestones for Acer’s OLPRUVA and celiprolol products within specified time periods. Certain additional cash payments are also possible pursuant to the CVRs with respect to milestones involving Acer’s early-stage program ACER-2820 (emetine). As of December 31, 2023, total shares of common stock outstanding were 41,534,668, and fully diluted common shares outstanding were 58,230,596, which included 5,603,729 shares issuable upon exercise of warrants. On March 25, 2024, the Audit Committee (the “Audit Committee”) of the Company’s Board of Directors, after discussion with senior management and the Company’s independent registered public accountants, concluded that the Company’s previously issued audited consolidated financial statements as of and for the fiscal years ended December 31, 2022 and December 31, 2021, included in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, (collectively, the “Prior Financial Statements”) should no longer be relied upon. In connection with the preparation of the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 (the “2023 Form 10-K”), the Audit Committee concluded that, in prior years it had not appropriately accounted for certain common stock warrants as liabilities. These errors led to understatements of derivative and warrant liability and additional paid-in capital and fluctuations in fair value adjustment related to derivative and warrant liability during the impacted periods. In addition, in connection with the restatements, the Company has concluded that the previously disclosed errors led to misstatements of fair value adjustment related to derivative and warrant liability, derivative and warrant liability, additional paid-in capital, and retained earnings/(accumulated deficit) that were previously disclosed in the unaudited condensed consolidated balance sheets and statements of operations included in the Company’s Quarterly Reports on Form 10-Q for the quarterly periods ended March 31, 2022, June 30, 2022, September 30, 2022, March 31, 2023, June 30, 2023 and September 30, 2023 (collectively, the “Prior Interim Financial Statements”). On March 25, 2024, the Audit Committee, after discussion with senior management and the Company’s independent registered public accountants, concluded that the Prior Interim Financial Statements should no longer be relied upon. The errors and corrective adjustments identified by the Company are non-cash in nature; and they do not impact results of operations or key metrics used by the Company in managing operations, such as revenue, operating expenses, and loss from operations. Conference Call Information Zevra will host a conference call and live audio webcast today at 4:30 p.m. ET, to discuss its corporate and financial results for Q4 and FY 2023. The audio webcast will be accessible via the Investor Relations section of the Company’s website, . An archive of the audio webcast will be available for 90 days beginning at approximately 5:30 p.m. ET, on March 28, 2024. Additionally, interested participants and investors may access the conference call by dialing either: (800) 245-3047 (U.S.) +1 (203) 518- 9765 (International) Conference ID: ZVRAQ423 About Urea Cycle Disorders UCDs are a group of rare, genetic disorders that can cause harmful ammonia to build up in the blood, potentially resulting in brain damage and neurocognitive impairments if ammonia levels are not controlled.i Any increase in ammonia over time is serious. Therefore, it is important to adhere to any dietary protein restrictions and have alternative medication options to help control ammonia levels. About OLPRUVA® OLPRUVA (sodium phenylbutyrate) was approved for the treatment of certain UCDs in December 2022 and has recently been marketed under the brand name, OLPRUVA®. OLPRUVA (sodium phenylbutyrate) for oral suspension is a prescription medicine used along with certain therapy, including changes in diet, for the long-term management of adults and children weighing 44 pounds (20 kg) or greater and with a body surface area (BSA) of 1.2 m2 or greater, with urea cycle disorders (UCDs), involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). Please see Important Safety Information and full Prescribing Information, including Patient Information. Important Safety Information Certain medicines may increase the level of ammonia in your blood or cause serious side effects when taken during treatment with OLPRUVA. Tell your doctor about all the medicines you or your child take, especially if you or your child take corticosteroids, valproic acid, haloperidol, and/or probenecid. OLPRUVA can cause serious side effects, including: 1) nervous system problems (neurotoxicity). Symptoms include sleepiness, tiredness, lightheadedness, vomiting, nausea, headache, confusion, 2) low potassium levels in your blood (hypokalemia) and 3) conditions related to swelling (edema). OLPRUVA contains salt (sodium), which can cause swelling from salt and water retention. Tell your doctor right away if you or your child get any of these symptoms. Your doctor may do certain blood tests to check for side effects during treatment with OLPRUVA. If you have certain medical conditions such as heart, liver or kidney problems, are pregnant/planning to get pregnant or breast-feeding, your doctor will decide if OLPRUVA is right for you. The most common side effects of OLPRUVA include absent or irregular menstrual periods, decreased appetite, body odor, bad taste or avoiding foods you ate prior to getting sick (taste aversion). These are not all of the possible side effects of OLPRUVA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. About Niemann-Pick Disease Type C (NPC) Niemann-Pick disease type C (NPC) is an ultra-rare, progressive, and neurodegenerative lysosomal storage disorder characterized by an inability of the body to transport cholesterol and other lipids within the cell, leading to an accumulation of these substances in various tissue areas, including brain tissue. The disease is caused by mutations in the NPC1 or NPC2 genes, which are responsible for making lysosomal proteins. Both children and adults can be affected by NPC with varying clinical presentations. Those living with NPC lose independence due to physical and cognitive limitations, with key neurological impairments presenting in speech, cognition, swallowing, ambulation, and fine motor skills. Disease progression is irreversible and can be fatal within months or take years to be diagnosed and advance in severity. About Arimoclomol Arimoclomol, Zevra’s orally delivered, first-in-class investigational product candidate for the treatment of NPC, has been granted Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, and Rare Pediatric Disease designation by the FDA, and Orphan Medicinal Product designation for the treatment of NPC by the European Medicines Agency (EMA). The FDA has accepted the resubmission of the NDA for arimoclomol and has set a user fee goal date (PDUFA date) of September 21, 2024. About Idiopathic Hypersomnia (IH) Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness (EDS). Patients with IH experience daytime lapses into sleep, or an irrepressible need to sleep that persists even with adequate or prolonged nighttime sleep. Additionally, those with IH have extreme difficulty waking, otherwise known as sleep inertia, severe brain fog, and often fall asleep unintentionally or at inappropriate times. These symptoms of IH often lead to further, even more debilitating problems such as memory lapses, difficulty maintaining focus, and depression. It is estimated, based on claims data, that approximately 37,000 patients in the United States are currently diagnosed with IH, although the total patient population may be much larger due to some patients who have not yet been diagnosed, have been misdiagnosed, or are not currently seeking treatment. About KP1077 KP1077 (serdexmethylphenidate or SDX) is Zevra’s proprietary prodrug of d-methylphenidate (d-MPH) and its sole active pharmaceutical ingredient (API). KP1077 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of IH, and the U.S. Drug Enforcement Agency (DEA) has classified SDX, the sole API in KP1077, as a Schedule IV controlled substance based on evidence suggesting SDX has a lower potential for abuse when compared to d-MPH, a Schedule II controlled substance. About Zevra Therapeutics Zevra Therapeutics is a rare disease company combining science, data, and patient needs to create transformational therapies for diseases with limited or no treatment options. Our mission is to bring life-changing therapeutics to people living with rare diseases. With unique, data-driven development and commercialization strategies, the Company is overcoming complex drug development challenges to make new therapies available to the rare disease community. Expanded access programs are made available by Zevra Therapeutics and its affiliates and are subject to the Company's Expanded Access Program (EAP) policy as published on its website at . Participation in these programs is subject to the laws and regulations of each jurisdiction under which each respective program is operated. Eligibility for participation in any such program is at the treating physician's discretion. For more information, please visit or follow us on X (formerly Twitter) and LinkedIn. Cautionary Note Concerning Forward-Looking Statements This press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that do not relate solely to historical or current facts, including without limitation statements regarding the promise and potential impact of our preclinical or clinical trial data, the initiation, timing and results of any clinical trials or readouts, the content, information used for, timing or results of any NDA submissions or resubmissions for arimoclomol or any other product candidates for any specific disease indication or at any dosage, the potential launch or commercialization of any of product candidates or products, the Company’s estimated extent of and impacts of the restatements and the timing of the filing of the 2023 Form 10-K, the sufficiency of our cash, cash equivalents and investments to fund our operating activities for any specific period of time, our plans to build out commercial teams for products or product candidates, and our strategic and product development objectives, including with respect to becoming a leading, commercially focused rare disease company. Forward-looking statements are based on information currently available to Zevra and its current plans or expectations. They are subject to several known and unknown uncertainties, risks, 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. These and other important factors are described in detail in the “Risk Factors” section of Zevra’s Annual Report on Form 10-K for the year ended December 31, 2022, as updated in Zevra’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, and Zevra’s other filings with the Securities and Exchange Commission. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. Although we believe the expectations reflected in such forward-looking statements are reasonable, we cannot assure that such expectations will prove correct. These forward-looking statements should not be relied upon as representing our views as of any date after the date of this press release. __________________________ i Ah Mew N, et al. Urea cycle disorders overview [updated June 22, 2017]. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews® [Internet]. University of Washington; 1993-2022. Accessed March 20, 2022. ZEVRA THERAPEUTICS, INC. STATEMENTS OF OPERATIONS (In thousands, except share and per share amounts) (Unaudited) Year Ended December 31, 2023 2022 (As Restated) Revenue, net $ 27,461 $ 10,161 Operating expenses: Cost of revenue 2,945 222 Research and development 39,806 19,803 Selling, general and administrative 34,314 15,038 Acquired in-process research and development - 17,663 Total operating expenses 77,065 52,726 Loss from operations (49,604 ) (42,565 ) Other (expense) income: Interest expense (1,501 ) (335 ) Fair value adjustment related to derivative and warrant liability (98 ) 15,159 Fair value adjustment related to investments 613 (577 ) Interest and other income, net 4,541 1,513 Total other income 3,555 15,760 Loss before income taxes (46,049 ) (26,805 ) Income tax (expense) benefit - 33 Net loss $ (46,049 ) $ (26,772 ) Basic and diluted net loss per share of common stock: Net loss $ (1.30 ) $ (0.78 ) Weighted average number of shares of common stock outstanding: Basic and diluted 35,452,460 34,488,800 ZEVRA THERAPEUTICS, INC. BALANCE SHEETS (In thousands, except share and par value amounts) (Unaudited) December 31, 2023 2022 (As Restated) Assets Current assets: Cash and cash equivalents $ 43,049 $ 65,466 Securities at fair value 24,688 16,900 Short-term investments - other - 481 Accounts and other receivables 17,377 8,299 Prepaid expenses and other current assets 1,824 1,688 Total current assets 86,938 92,834 Inventories 9,841 671 Property and equipment, net 736 794 Operating lease right-of-use assets 790 988 Goodwill 4,701 - Long-term investments - other - 20,000 Intangible assets, net 69,227 - Other long-term assets 94 53 Total assets $ 172,327 $ 115,340 Liabilities and stockholders’ equity Current liabilities: Accounts payable and accrued expenses $ 28,403 $ 6,169 Line of credit payable 37,700 12,800 Current portion of operating lease liabilities 543 480 Current portion of discount and rebate liabilities 4,550 4,655 Other current liabilities 2,524 719 Total current liabilities 73,720 24,823 Secured promissory note 5,066 - Derivative and warrant liability 16,100 10,202 Operating lease liabilities, less current portion 456 843 Discount and rebate liabilities, less current portion 7,663 4,327 Other long-term liabilities 7,458 25 Total liabilities 110,463 40,220 Commitments and contingencies Stockholders' equity: Preferred stock: Undesignated preferred stock, $0.0001 par value, 10,000,000 shares authorized, no shares issued or outstanding as of December 31, 2023 or December 31, 2022 - - Common stock, $0.0001 par value, 250,000,000 shares authorized, 43,110,360 shares issued and 41,534,668 shares outstanding as of December 31, 2023; 35,450,257 shares issued and 34,540,304 shares outstanding as of December 31, 2022 4 3 Additional paid-in capital 472,664 436,269 Treasury stock, at cost (10,983 ) (7,536 ) Accumulated deficit (399,778 ) (353,729 ) Accumulated other comprehensive income (43 ) 113 Total stockholders' equity 61,864 75,120 Total liabilities and stockholders' equity $ 172,327 $ 115,340 Zevra Contact Nichol Ochsner +1 (732) 754-2545 nochsner@zevra.com Russo Partners Contacts Adanna G. Alexander, Ph.D. +1 (646) 942-5603 adanna.alexander@russopartnersllc.com

5月30-31日 第八届广州生物医药创新者峰会 扫码立即报名 注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。近年来，罕见病是药企乃至整个社会都很关心的话题。罕见病通常指发病率极低的疾病，又称“孤儿病”。世界各国根据各自实际情况，在罕见病的定义上略有不同。美国将罕见病定义为患者少于20万人/年或其治疗药物销售额预期 难以收回研发成本的疾病；欧盟将患病率小于0.5‰、能导致衰弱或威胁生命的疾病定义为 罕见病；日本将患者少于 5万/年或患病率小于0.5‰作为罕见病定义标准。我国在2021年《中国罕见病定义研究 报告 2021》中将罕见病定义为“新生儿发病率小于1/万、患病率小于1/万且患病人数小于14万的疾病”。其中，80%的罕见病是由遗传缺陷或基因突变造成的，而细胞与基因疗法也正成为罕见病药物研发的热点：相对于常见疾病，罕见病通常由单个基因突变引起，是基因治疗的理想靶标；约有超过90%的罕见病目前缺乏有效治疗药物，基因和细胞治疗作为一种潜在的创新方法，有望为罕见病治疗带来突破性改善。细胞与基因疗法在治疗罕见病方面已展现出重大进展，有望为全球2.6-4.5亿受罕见病影响的人群（包括儿童）带来治愈希望。今天药融圈要介绍的这家公司叫Ultragenyx，它的产品和研发管线均是罕见病药物。Ultragenyx Pharmaceutical（纳斯达克股票代码：RARE）于2010年在硅谷成立，是一家专注于罕见病药物研发与商业化美国生物技术公司。经过2轮融资后，于2014年成功在纳斯达克上市。（截至2024年3月8日，该公司股价50.53美元/股，市值约41.6亿美元。3月26日，市值为37.43亿美元。）其创始人、总裁兼首席执行官Emil Kakkis曾在Harbour-UCLA医疗中心工作，并开发一种针对罕见疾病MPS I 的酶替代疗法。目前，Ultragenyx公司拥有一支在罕见病治疗开发和商业化方面经验丰富的管理团队，在团队的努力下，公司已有4款产品上市，且建立起了一个多元化的候选疗法管线，旨在解决未被满足的医疗需求。其中，Crysvita被批准用于治疗X连锁低磷血症（XLH），以及肿瘤性低磷骨软化症（TIO）。管线布局&产品Ultragenyx目前批准的疗法和临床阶段的产品线包括四个产品类别：生物制剂、小分子、AAV基因疗法和核酸候选药物，有四种已获商业上市批准的产品：用于治疗X-连锁低磷血症（XLH）和肿瘤诱导的骨软化症（TiO）的Crysvita®（burosumab）、用于儿童和成年人黏多糖贮积症VII型（MPSVII）或SLY综合征的Mepsevii®（vestronidase Alfa）、用于治疗长链脂肪酸氧化障碍（LC-FAOD）的Dojolvi®（triheptanoin）和用于治疗家族性高胆固醇血症（HoFH）的Evkeeza®（evinacumab）。上市产品1.Crysvita®（burosumab/布罗索尤单抗）CRYSVITA于2018年4月在美国获批上市。CRYSVITA是成纤维细胞生长因子23 (fibroblast growth factor23, FGF23)的阻断抗体。当时获批的适应症是6个月以上的儿童及成人X连锁低磷酸盐血症(X-linked hypophosphatemia, XLH, 又名：家族性低磷酸血症佝偻病)。XLH是一种罕见的、遗传性的、进行性的和终生的骨骼肌肉系统疾病。其病因是体内调磷因子FGF23产生过多或降解障碍，使循环中FGF23水平增加，导致肾脏排磷增多及低磷血症。估计所有的发达国家中有约48,000个病人，包含约36,000成人和12,000儿童。在2020年6月，FDA批准了CRYSVITA的第2个适应症：2岁及以上的儿童及成人肿瘤性骨软化症的低磷酸盐血症(FGF23相关)。肿瘤性骨软化症通常是由产生过量FGF23的良性肿瘤所引起的，该病将会导致严重的低磷酸盐血症、骨折以及肌无力。一般首选的治疗方案是手术切除肿瘤，但对于某些患者，肿瘤无法切除或肿瘤切除后复发。对于这些患者仍然存在着巨大的未满足临床需求。估计所有的发达国家肿瘤性骨软化症的患者数量约为2,000-4,000。除了在美国，目前CRYSVITA还在加拿大，欧洲地区(欧盟、英国、瑞士等)，南美， 土耳其等地获批。Ultragenyx正在与日本巨头协和麒麟/Kyowa Kirin Co.，Ltd.（简称KKC）以及KKC的全资子公司Kyowa Kirin合作，在全球范围内开发和商业化Crysvita。中国也已经获批上市。2.Mepsevii®（vestronidase Alfa）MEPSEVII于2017年11月在美国获批上市。该药是一种重组人溶酶体β葡萄糖醛酸酶(酶替代疗法)，用于儿童和成年人黏多糖贮积症VII型(MPS VII，斯莱综合征【Sly syndrome】)的治疗。黏多糖贮积症(mucopolysaccharidosis，MPS)是一组复杂的、进行性多系统受累的溶酶体病，是由于降解糖胺聚糖的酶缺乏所致。黏多糖贮积症共分为7型。黏多糖贮积症VII型是最罕见的溶酶体贮积症亚型之一，估计所有的发达国家中只有约200个病人，国内目前仍然缺乏大样本流行病学数据。VII型通常会导致多器官功能衰竭，广泛性骨骼功能障碍和死亡。除了在美国，目前MEPSEVII还在欧盟、英国，巴西和墨西哥获批。3.Dojolvi®（triheptanoin）Dojolvi于2020年6月在美国获批上市。该药是一种高纯度的、合成的7碳脂肪酸甘油三酯。它是一种中链、奇数碳脂肪酸，可作为能量来源及体内各反应的代谢产物的替代品，用来治疗儿童和成人长链脂肪酸氧化障碍(Long-chain fatty acid oxidation disorders, LC-FAOD) 。LC-FAOD是一组罕见的代谢性疾病，该病会抑制脂肪代谢，阻止脂肪转化为能量，并可能导致低血糖、肌肉撕裂、心脏以及肝脏疾病。估计所有的发达国家中有约8,000-14,000个病人。4.Evkeeza®（evinacumab）药融云数据（www.pharnexcloud.com）显示：Evkeeza是一种通过静脉注射给药的全人单克隆抗体，可结合并阻断血管生成素样蛋白3（ANGPTL3）的功能，ANGPTL3是一种在脂质代谢中起关键作用的蛋白质，用于治疗纯合子家族性高胆固醇血症（HoFH）。Evinacumab是Evkeeza中的活性成分，它能结合到体内的一种名为ANGPTL3的蛋白，并阻断其作用。ANGPTL3涉及控制胆固醇水平，阻断其作用可降低血液中的胆固醇水平。Evkeeza通过每月（4周）一次的输注给药。本品为与再生元联合开发。（关联阅读：再生元进击千亿美金俱乐部，减重领域或将续写传奇）药融云数据，www.pharnexcloud.comHoFH是一种极为罕见的遗传性疾病，是家族性高胆固醇血症（FH）中最严重的一种。Evkeeza是美国和欧盟批准的首个ANGPTI-3靶向疗法，用于辅助治疗12岁及以上HoFH患者。目前，Evkeeza正被评估用于5-11岁HoFH患者。在美国以外的发达国家，大约有3，000到5，000名HoFH患者。据估计，每100万人中约有4人患有HoFH，而且由于患者稀少，Evkeeza的治疗成本巨大，平均每年约45万美元。管线更新和临床里程碑1. UX143（Setrusumab）单克隆抗体治疗成骨不全症（OI）：ORBIT研究的3期部分预计将于2024年第一季度末全部纳入在后期临床试验Orbit和Cosmic中，患者正在接受给药，这些试验正在评估setrusumab在儿童和年轻成人OI患者中的应用。ORBIT研究的随机、安慰剂对照3期部分预计将招募约150名患者，并于2024年第一季度末全部招募。ORBIT研究的其他长期2期安全性和有效性数据预计将于2024年下半年公布。3期COSMIC研究是一项活性对照研究，旨在评估setrusumab与静脉注射双膦酸盐（IV-BP）治疗相比，对2至5岁以下患者的年度总骨折率的影响。Cosmic预计将在全球20多个地点招募约50名或更多患者，预计将于2024年上半年完成招募。2. GTX-102反义寡核苷酸治疗Angelman综合征:1/2期完全入组；预计2024年上半年的扩张数据 扩大队列的招募工作于2023年12月完成，共招募了53名新患者。共有74名患者参加了1/2期研究，包括剂量递增/扩展研究患者。扩展队列将评估许多与先前纳入的剂量递增/扩展队列相同的安全性、药代动力学和疗效指标，以及一些新的评估。下一次安全性和有效性更新预计将于2024年上半年进行，并计划纳入至少20名扩展队列患者的数据，其中至少有170天的数据。2024年1月，GTX-102被欧洲药品管理局（EMA）纳入优先药品（PRIME）计划。PRIME由欧洲药品管理局（EMA）授予那些根据早期临床数据显示有潜力使需求未得到满足的患者受益的药物。通过PRIME，EMA提供早期和主动支持，以优化开发计划，生成有关药物效益和风险的可靠数据，并加快对药物应用的评估。3. UX701 AAV基因治疗Wilson病：队列3中最后一名患者给药；预计中期第一阶段数据将于2024年中期发布 第1阶段的三个剂量递增队列中的所有患者均已给药。在第1阶段，将评估UX701的安全性和有效性，并在第2阶段（该研究的关键、随机、安慰剂对照阶段）选择剂量进行进一步评估。第一阶段的数据预计将在2024年中期公布，随后将在2024年下半年进行剂量选择并启动第二阶段。4. UX111 AAV基因治疗Sanfilippo综合征（MPS IIIA）：2024年2月初，该公司在第20届年度世界研讨会（WorldSymposium™）上公布了一项正在进行的关键转移（Pivotal Transfer）研究的新的积极数据，该研究评估了UX111在患有MPS IIIA的儿童中的安全性和有效性，显示单次输注UX111可以显著纠正潜在的代谢疾病，并维持几乎所有患者的认知功能。该报告还显示，观察到的脑脊液中硫酸乙酰肝素暴露的减少可以预测UX111治疗后MPS IIIA患者的长期认知功能的改善。有了这些数据和其他数据，正在与FDA进行讨论，以寻求UX111的加速审查路径。5. DTX401 AAV基因治疗Ia型糖原贮积病（GSDIA）:3期研究完成给药；第3阶段数据读出预计在2024年上半年。2023年5月，Ultragenyx宣布最后一名患者在3期研究中接受了给药。这项为期48周的研究纳入了8岁及以上的患者，按1:1的比例随机分配至DTX401或安慰剂组。3期安全性和有效性数据预计将于2024年上半年公布。DTX301 AAV基因治疗鸟氨酸氨甲酰转移酶（OTC）缺乏症:3期研究给药患者；预计招生工作将于2024年上半年完成 在正在进行的3期研究中，Ultragenyx正在对患者进行随机分组和给药。关键的64周研究将包括约50名患者，按1:1随机分配至DTX301或安慰剂组。主要终点是通过去除氨清除剂药物和蛋白质限制饮食以及24小时氨水平的变化来测量的反应。招募工作预计将于2024年上半年完成。财务状况2024年2月22日，Ultragenyx公布2023财年年报。2023年Ultragenyx总营收为4.34亿美元，其中Crysvita收入3.25 ~ 3.3 亿美元；预计公司2024年总营收达到5.3亿美元。截至2023年末，该公司现金、现金等价物和有价债务证券约7.76亿美元。与2022财年相比，2023财年Ultragenyx的产品销售额增加了6150万美元。这一增长主要是由于拉丁美洲对Crysvita的需求增加，原因是接受治疗的患者数量增加，对其他批准产品的需求持续增加，以及指定患者计划的收入增加；Crysvita合作收入和特许权收入净增加了1560万美元。Crysvita收入的增加主要是由于接受治疗的患者数量增加；从Daiichi Sankyo/第一三共中获得的收入减少了620万美元，减少原因是2023年完成了技术转让和技术转让期。下表是按主要项目类型和业务活动划分的研发费用明细（千美元）:与2022财年相比，2023财年Ultragenyx的研发费用总额减少了5730万美元，主要由于：• 对于基因治疗项目，增加1500万美元，主要与2022年5月从Abeona Therapeutics收购的UX111项目的开发成本增加以及内部制造的生产材料采购增加有关，部分被DTX401的外部临床制造费用的减少所抵消；• 对于生物和核酸项目，增加1160万美元，主要与UX143和GTX102项目的持续临床进展以及相关的临床开发和制造费用有关，部分被用于治疗III型糖原贮积病的UX053开发费用的减少所抵消；• 对于转化研究，减少了960万美元，主要与IND阶段项目的制造和员工人数费用减少有关；• 前期许可、收购和里程碑费用减少6600万美元，原因是截至2023年12月31日确认的UX143项目临床登记里程碑的费用为900万美元，而截至2022年12月31日收购Genetx的费用为7500万美元；• 对于批准的产品，减少2220万美元，主要是由于北美的Crysvita商业化责任转移到KKC，以及Dojolvi实现了成本效益，部分抵消了Regeneron协作费用的报销以及Evkeeza人员和产品发布成本的增加；截至2023年12月31日，Ultragenyx拥有7.771亿美元的可用现金、现金等价物和可出售的债务证券，该公司称其现有资产将足以满足至少未来12个月的运营需求。参考：NMPA/CDE；药融云数据，www.pharnexcloud.com；FDA/EMA/PMDA；相关公司公开披露；https://www.ultragenyx.com/；https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-reports-fourth-quarter-and-full-year-2023-financial；https://www.sec.gov/Archives/edgar/data/1515673/000095017024017879/rare-20231231.htm；https://mp.weixin.qq.com/s/-2XHmyVS_hIOqNfvFBzoGQ；https://www.sec.gov/Archives/edgar/data/1515673/000119312523259557/d542322d424b5.htm；https://mp.weixin.qq.com/s/V8pzc7DjO7oqn2mmm9PPdw；等等。本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐 活动推荐  8月 • NDC2024生物医药创新博览会  关键词：  抗体、多肽、核酸、核药，XDC、小分子、注册、临床、CMC（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

Initiated final IND/CTA enabling studies for lead in vivo gene editing program PBGENE-HBV; expect to submit IND and/or CTA in 2024 Completed licensing agreements to monetize divested CAR T assets with Imugene, TG Therapeutics and Caribou Biosciences including nearly $50 million in upfront and potential near-term payments Completed $40 million in public offering extending our anticipated cash runway into the second half of 2026 which is expected to enable achievement of first-in-human Phase 1 clinical data for two wholly owned programs - Hepatitis B & Primary Mitochondrial Myopathy DURHAM, N.C.--(BUSINESS WIRE)-- Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS® platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene elimination, insertion, and excision, today announced financial results for the fourth quarter and fiscal year ended December 31, 2023 and provided a business update. “2023 was a transformative year for Precision BioSciences as we fully transitioned to our core capability as an in vivo gene editing company rapidly advancing development of our wholly owned in vivo programs led by PBGENE-HBV and quickly followed by PBGENE-PMM. As a part of this transition, we successfully monetized our prior CAR T investments and completed a $40 million public offering, strengthening our balance sheet beyond Phase 1 readouts for both wholly owned programs,” said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences. “We are well positioned to continue to execute against our objectives, having received regulatory feedback from the U.S. Food and Drug Administration (FDA) and key regulatory agencies outside the U.S. which provided clarity and alignment to guide our planned investigational new drug (IND) and/or clinical trial application (CTA) filings for PBGENE-HBV in 2024. In addition, our partner iECURE has advanced the first ARCUS-mediated gene editing program into the clinic, bolstering our confidence and establishing regulatory precedent for ARCUS in vivo gene editing programs with the potential to deliver a curative treatment for patients.” “As we look ahead, we continue to advance our focused strategy to differentiate ARCUS within the gene editing field and progress both our wholly owned and partnered gene editing programs. In our wholly owned pipeline, we plan to continue to advance PBGENE-HBV and PBGENE-PMM towards IND and/or CTA filings in 2024 and 2025, respectively, as well as commence a new gene insertion program of our own. More broadly, we anticipate presenting and publishing new data this year that further differentiates ARCUS as a potential best-in-class tool for high efficiency gene insertion via homology directed repair. We believe that these complementary objectives will continue to build momentum and establish Precision BioSciences as a leading in vivo gene editing company,” added Mr. Amoroso. Wholly Owned Portfolio PBGENE-HBV (Viral Elimination Program): Precision is developing PBGENE-HBV for the treatment of patients with chronic hepatitis B. Currently, it is estimated that approximately 300 million people worldwide are afflicted with chronic Hepatitis B. In November 2023, Precision presented preclinical efficacy and safety data at the 2023 American Association for the Study of Liver Diseases Annual Meeting. The data demonstrated strong proof of concept efficacy and safety for the final clinical candidate including no detectable off-target editing at maximal on-target editing dose. In February 2024, Precision announced that the company had received pre-IND regulatory feedback from the U.S. FDA in addition to regulatory feedback from agencies outside the U.S. providing clarity and alignment on PBGENE-HBV IND/CTA-enabling preclinical plans and clinical strategy. Precision expects to submit an IND and/or CTA for this program in 2024. PBGENE-PMM (Mutant Mitochondrial DNA Elimination Program): PBGENE-PMM is a first of its kind potential treatment for m.3243-associated primary mitochondrial myopathy (PMM). Mitochondrial diseases are the most common hereditary metabolic disorder in the world, affecting 15,000 to 25,000 people in the U.S. alone. PMM currently lacks a curative treatment and impacts approximately 50% of patients with mitochondrial disease. In a 2023 publication in Nature Metabolism, Precision shared new pre-clinical data highlighting the high specificity of the mitoARCUS nucleases to edit and eliminate mutant mitochondrial DNA while allowing wild-type (normal) mitochondrial DNA to repopulate in the mitochondria, thus improving normal function. ARCUS nucleases are able to penetrate the mitochondrial membrane unlike CRISPR-Cas, base and prime editors because ARCUS is single component editor that does not require a guide RNA. Precision expects to submit an IND and/or CTA for this program in 2025. Partnered Programs iECURE-OTC (Gene Insertion Program): Led by iECURE, ECUR-506 is the first ARCUS-mediated gene editing program to advance into the clinic following approval from the Australian Therapeutic Goods Administration and the U.K. Medicines & Healthcare products Regulatory Agency (MHRA) for initiation of the OTC-HOPE study, in the first half of 2024. The OTC-HOPE study is a first-in-human Phase 1/2 trial evaluating ECUR-506 as a potential treatment for neonatal onset ornithine transcarbamylase (OTC) deficiency. Non-human primate (NHP) data presented by researchers from the University of Pennsylvania’s Gene Therapy Program demonstrated sustained gene insertion of a therapeutic OTC transgene one-year post-dosing in newborn and infant NHP’s with high efficiency. PBGENE-NVS (Gene Insertion Program): Precision continues to advance its gene editing program with Novartis to develop a custom ARCUS nuclease for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia. The collaborative intent is to insert, in vivo, a therapeutic transgene as a potential one-time transformative treatment administered directly to the patient to overcome disparities in patient access to treatment with other therapeutic technologies, including those that are targeting an ex vivo gene editing approach. PBGENE-DMD (Gene Excision Program): Precision continues its in vivo gene editing collaboration with Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly and Company (Lilly), in applying ARCUS nucleases to three initial targets, including Duchenne muscular dystrophy (DMD) in muscle, a central nervous system directed target, and a liver directed target. The goal of the PBGENE-DMD program is to utilize a pair of ARCUS nucleases, delivered by a single adeno-associated virus (AAV), that are designed to excise an approximately 500,000 base pair mutation “hot spot” region from the dystrophin gene to generate a variant of the dystrophin protein that is functionally competent. During the Company’s September 2023 R&D Day, Precision highlighted preclinical data demonstrating the potential of ARCUS in vivo gene editing for large gene excisions and that the edited dystrophin variant was observed in multiple tissue types frequently involved in progression of DMD, including skeletal muscle, heart, and diaphragm, enabling significantly improved muscle function. PBGENE-LLY2 (Gene Insertion Program): During the Precision 2023 Gene Editing R&D Day, Precision highlighted new data demonstrating that ARCUS is capable of high efficiency gene insertion in nondividing cells in adult nonhuman primates, the most challenging context for gene insertion. In the pre-clinical study involving coadministration of AAV and lipid nanoparticle, Precision scientists observed 40% to 45% overall gene insertion efficiency at 1- and 3-months. Precision scientists largely attribute this high efficiency to the unique ARCUS cut type which drives homology directed repair, even in nondividing cells. Business Updates – Monetization of CAR T Investments: Completed Licensing Deal with TG Therapeutics for Cell Therapy Azer-Cel in Autoimmune Diseases: In January 2024, Precision announced the completion of a transaction with TG Therapeutics (Nasdaq: TGTX) for certain exclusive and non-exclusive license rights to develop Azercabtagene Zapreleucel (azer-cel) for autoimmune diseases and other indications outside of cancer. In exchange for these rights, Precision received upfront and potential near-term economics valued at $17.5 million. The upfront payment of $7.5 million consisted of cash and the purchase of 97,360 shares of Precision common stock by TG Therapeutics at a price of $23.10 per share, a 100% premium to the 30-day volume-weighted average price. Shares and per share amounts have been adjusted for Precision’s reverse stock split effective February 14, 2024. In addition, Precision will receive $2.5 million in deferred consideration due within 12 months as an equity investment in Precision’s common stock at a 100% premium to the then 30-day VWAP prior to purchase. Upon the achievement of certain near-term clinical milestones, Precision will receive an additional $7.5 million payment in cash and the purchase of Precision common stock by TG Therapeutics at a 100% premium to the then current 30-day VWAP. Precision is eligible to receive up to $288 million in additional milestone payments based on the achievement of certain clinical, regulatory, and commercial milestones, in addition to high-single-digit to low-double-digit royalties on net sales. Completed Licensing Deal with Imugene Limited for Azer-Cel in Cancer: The agreement with TG Therapeutics followed an agreement with Imugene Limited (ASX: IMU) in August 2023 for an exclusive license for azer-cel in cancer. In exchange for global rights to azer-cel for cancer Precision received upfront economics valued at $21 million consisting of cash and convertible notes. In addition, Precision is eligible for a potential $8 million near-term payment in cash and equity upon successful completion of the phase 1b dosing in the CAR T relapsed LBCL patient population. Precision is eligible to receive up to $198 million in additional milestone payments and double-digit royalties on net sales of azer-cel. Completed Non-Exclusive Patent License Agreement with Caribou Biosciences: In February 2024, Precision announced that it had granted Caribou Biosciences (Nasdaq: CRBU) a non-exclusive, worldwide license, with the right to sublicense, to one of Precision’s foundational cell therapy patent families for use with CRISPR-based therapies in the field of human therapeutics. Under the terms of the agreement, Precision received an upfront payment and, upon commercialization by Caribou, will receive royalties on net sales of licensed products. In addition, for each occurrence of certain strategic transactions involving Caribou, Precision is entitled to receive a specific tiered milestone payment. In total, these three transactions provide Precision BioSciences with nearly $50 million in upfront payments and potential near-term cash payments which, if realized, will be invested in the in vivo gene editing programs. Business Updates – $40 Million Offering: On March 1, 2024, Precision completed a $40 million public underwritten offering consisting of 2,500,000 shares of its common stock and accompanying warrants to purchase up to 2,500,000 shares of common stock at a combined offering price of $16.00 price per share, for total gross proceeds of $40 million, before deducting underwriting discounts and commissions. The financing included participation from leading life sciences investors, including Perceptive Advisors, Janus Henderson Investors, Aquilo Capital Management, LLC and LYFE Capital. The capital raised in the public offering is expected to extend the company’s cash runway into the second half of 2026, fund development of our PBGENE-HBV and PBGENE-PMM in vivo gene editing programs through Phase 1 read out, and enable commencement of a new wholly owned gene insertion program. Quarter Ended December 31, 2023 Financial Results: Cash and Cash Equivalents: As of December 31, 2023, Precision had $116.7 million in cash and cash equivalents. The cash balance as of December 31, 2023 does not include the benefit of cash received from TG Therapeutics, Caribou or the $40 million capital raise since year-end. Upfront and potential near-term cash from CAR T transactions, cash received from the public offering, along with existing cash and cash equivalents, expected operational receipts, continued fiscal and operating discipline, availability of Precision’s at-the-market (ATM) facility, and available credit are expected to extend Precision’s cash runway into the second half of 2026. Revenues: Total revenues for the quarter ended December 31, 2023 were $7.0 million, as compared to $10.6 million for the quarter ended December 31, 2022. The decrease of $3.6 million in revenue during the quarter ended December 31, 2023 was primarily the result of a decrease in revenue recognized from collaborations. Research and Development Expenses: Research and development expenses were $13.4 million for the quarter ended December 31, 2023, as compared to $12.7 million for the quarter ended December 31, 2022. The increase of $0.7 million was primarily due to an increase in PBGENE-HBV and PBGENE-PMM program costs as the programs continue to advance toward the clinic. General and Administrative Expenses: General and administrative expenses were $8.5 million for the quarter ended December 31, 2023, as compared to $10.0 million for the quarter ended December 31, 2022. The decrease of $1.5 million was primarily due to operational discipline, a decrease in the number of employees and a decrease in share-based compensation expense. Other Income and Expense: Total other income was $1.5 million for the quarter ended December 31, 2023, as compared to total other expense of $7.3 million for the quarter ended December 31, 2022. The increase was primarily driven by an impairment related to the iECURE PCSK9 collaboration in the quarter ended December 31, 2022, and a gain in fair value of equity investment in iECURE in the quarter ended December 31, 2023, partially offset by a loss from equity method investments. Continuing Operations: Loss from continuing operations was $13.4 million for the quarter ended December 31, 2023, as compared to $19.4 million for the quarter ended December 31, 2022. Net Loss: Net loss was $16.3 million, or $(4.06) per share (basic and diluted), including a $2.9 million loss from discontinued operations for the quarter ended December 31, 2023. Net loss was $28.5 million, or $(7.70) per share (basic and diluted), including a $9.1 million loss from discontinued operations for the quarter ended December 31, 2022. Discontinued operations represent costs associated with the development of allogeneic CAR T immunotherapies. Fiscal Year 2023 Financial Results: Revenues: Total revenues for the year ended December 31, 2023 were $48.7 million, as compared to $25.1 million for the year ended December 31, 2022. The increase of $23.6 million in revenue during the year ended December 31, 2023 was primarily the result of an increase in revenue recognized under the Prevail and Novartis agreements. Research and Development Expenses: Research and development expenses were $53.4 million for the year ended December 31, 2023, as compared to $46.1 million for the year ended December 31, 2022. The increase of $7.3 million was primarily due to an increase in PBGENE-HBV and PBGENE-PMM program costs as the programs continue to advance toward the clinic in addition to increases in outsourced research and development costs primarily related to consulting fees, employee-related costs, and facility-related costs. General and Administrative Expenses: General and administrative expenses were $39.1 million for the year ended December 31, 2023, as compared to $41.3 million for the year ended December 31, 2022. The decrease of $2.2 million was a result of operational discipline, lower headcount, and decreases in share-based compensation expense. Other Income and Expense: Total other income was $1.2 million for the year ended December 31, 2023, as compared to total other expense of $10.6 million for the year ended December 31, 2022. The increase was primarily driven by an impairment related to the iECURE PCSK9 collaboration in the year ended December 31, 2022, an increase in interest income, and an increase in the loss from equity method investments. Continuing Operations: Loss from continuing operations was $42.5 million for the year ended December 31, 2023, as compared to $72.9 million for the year ended December 31, 2022. Net Loss: Net loss was $61.3 million, or $(15.96) per share (basic and diluted), including a $18.8 million loss from discontinued operations for the year ended December 31, 2023. Net loss was $111.6 million, or $(38.10) per share (basic and diluted), including a $38.7 million loss from discontinued operations for the year ended December 31, 2022. Discontinued operations represent costs associated with the development of allogeneic CAR T immunotherapies. About Precision BioSciences, Inc. Precision BioSciences, Inc. is an advanced gene editing company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform that differs from other technologies in the way it cuts, its smaller size, and its simpler structure. Key capabilities and differentiating characteristics may enable ARCUS nucleases to drive more intended, defined therapeutic outcomes. Using ARCUS, the Company’s pipeline is comprised of in vivo gene editing candidates designed to deliver lasting cures for the broadest range of genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit . The ARCUS® platform is being used to develop in vivo gene editing therapies for sophisticated gene edits, including gene insertion (inserting DNA into gene to cause expression/add function), excision (removing a large portion of a defective gene by delivering two ARCUS nucleases in a single AAV), and elimination (removing a genome e.g. viral DNA or mutant mitochondrial DNA). 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, without limitation, statements regarding the clinical development and expected safety, efficacy and benefit of our product candidates (including azer-cel) and gene editing approaches including editing efficiency and differentiating aspects; the suitability of azer-cel for oncology indications and non-oncology indications including immunological diseases; the suitability of ARCUS nucleases for gene insertion, gene elimination, large gene deletion, and other gene editing approaches; the expected timing of regulatory processes (including filings and studies for PBGENE-HBV and PBGENE-PMM); expectations about our operational initiatives and business strategy; expectations of further presentations and publications further differentiating ARCUS; expectations and updates around partnership and collaboration opportunities; our expected cash runway and available credit; the sufficiency of our cash runway and available credit extending through clinical phase 1 readouts for our HBV and PPM programs; expectations about achievement of key milestones and receipt of any milestone, royalty, or other payments; expectations regarding our liquidity and capital resources; and anticipated timing of initial clinical data. In some cases, you can identify forward-looking statements by terms such as “aim,” “anticipate,” “approach,” “believe,” “contemplate,” “could,”, “designed”, “estimate,” “expect,” “goal,” “intend,” “look,” “may,” “mission,” “plan,” “possible,” “potential,” “predict,” “project,” “pursue,” “seek,” “should,” “target,” “will,” “would,” or the negative thereof and similar words and expressions. Forward-looking statements are based on management’s current expectations, beliefs and assumptions and on information currently available to us. These statements are neither promises nor guarantees, and involve a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors, including, but not limited to, our ability to become profitable; our ability to procure sufficient funding to advance our programs; risks associated with our capital requirements, anticipated cash runway, requirements under our current debt instruments and effects of restrictions thereunder, including our ability to raise additional capital due to market conditions and/or our market capitalization; our operating expenses and our ability to predict what those expenses will be; our limited operating history; the progression and success of our programs and product candidates in which we expend our resources; our limited ability or inability to assess the safety and efficacy of our product candidates; the risk that other genome-editing technologies may provide significant advantages over our ARCUS technology; our dependence on our ARCUS technology; the initiation, cost, timing, progress, achievement of milestones and results of research and development activities and preclinical and clinical studies, including clinical trial and investigational new drug applications; public perception about genome editing technology and its applications; competition in the genome editing, biopharmaceutical, and biotechnology fields; our or our collaborators’ or other licensees’ ability to identify, develop and commercialize product candidates; pending and potential product liability lawsuits and penalties against us or our collaborators or other licensees related to our technology and our product candidates; the U.S. and foreign regulatory landscape applicable to our and our collaborators’ or other licensees’ development of product candidates; our or our collaborators’ or other licensees’ ability to advance product candidates into, and successfully design, implement and complete, clinical or field trials; potential manufacturing problems associated with the development or commercialization of any of our product candidates; our ability to obtain an adequate supply of T cells from qualified donors; delays or difficulties in our and our collaborators’ and other licensees’ ability to enroll patients; changes in interim “top-line” and initial data that we announce or publish; if our product candidates do not work as intended or cause undesirable side effects; risks associated with applicable healthcare, data protection, privacy and security regulations and our compliance therewith; our or our licensees’ ability to obtain orphan drug designation or fast track designation for our product candidates or to realize the expected benefits of these designations; our or our collaborators’ or other licensees’ ability to obtain and maintain regulatory approval of our product candidates, and any related restrictions, limitations and/or warnings in the label of an approved product candidate; the rate and degree of market acceptance of any of our product candidates; our ability to effectively manage the growth of our operations; our ability to attract, retain, and motivate executives and personnel; effects of system failures and security breaches; insurance expenses and exposure to uninsured liabilities; effects of tax rules; effects of the COVID-19 pandemic and variants thereof, or any pandemic, epidemic, or outbreak of an infectious disease; the success of our existing collaboration agreements, and our ability to enter into new collaboration arrangements; our current and future relationships with and reliance on third parties including suppliers and manufacturers; our ability to obtain and maintain intellectual property protection for our technology and any of our product candidates; potential litigation relating to infringement or misappropriation of intellectual property rights; effects of natural and manmade disasters, public health emergencies and other natural catastrophic events; effects of sustained inflation, supply chain disruptions and major central bank policy actions; market and economic conditions; risks related to ownership of our common stock, including fluctuations in our stock price; our ability to meet the requirements of and maintain listing of our common stock on Nasdaq or other public stock exchanges; and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the quarterly period ended December 31, 2023, as any such factors may be updated from time to time in our other filings with the SEC, which are accessible on the SEC’s website at and the Investors page of our website under SEC Filings at investor.precisionbiosciences.com. All forward-looking statements speak only as of the date of this press release and, except as required by applicable law, we have no obligation to update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Precision Biosciences, Inc. Statements of Operations (In thousands, except share and per share amounts) For the Three Months Ended December 31, 2023 2022 Revenue $ 7,038 $ 10,598 Operating expenses Research and development 13,389 12,683 General and administrative 8,539 10,024 Total operating expenses 21,928 22,707 Operating loss (14,890 ) (12,109 ) Other income (expense): Impairment charges — (10,844 ) Loss on disposal of assets (524 ) (19 ) Gain (loss) on changes in fair value 1,603 (510 ) (Loss) gain from equity method investment (871 ) 2,604 Interest expense (579 ) (486 ) Interest income 1,827 1,937 Total other income (expense) 1,456 (7,318 ) Loss from continuing operations $ (13,434 ) $ (19,427 ) Loss from discontinued operations (2,855 ) (9,061 ) Net Loss $ (16,289 ) $ (28,488 ) Net loss per share attributable to common stockholders-basic and diluted $ (4.06 ) $ (7.70 ) Weighted average shares of common stock outstanding-basic and diluted 4,010,467 3,698,456 Precision Biosciences, Inc. Statements of Operations (In thousands, except share and per share amounts) For the Years Ended December 31, 2023 2022 Revenue $ 48,727 $ 25,098 Operating expenses Research and development 53,375 46,122 General and administrative 39,088 41,284 Total operating expenses 92,463 87,406 Operating loss (43,736 ) (62,308 ) Other income (expense): Impairment charges — (10,844 ) Loss on disposal of assets (461 ) (30 ) Gain (loss) on changes in fair value 1,145 (510 ) Loss from equity method investment (4,931 ) (1,579 ) Interest expense (2,230 ) (1,111 ) Interest income 7,686 3,473 Total other income (expense) 1,209 (10,601 ) Loss from continuing operations $ (42,527 ) $ (72,909 ) Loss from discontinued operations (including gain on disposal of $8,446 during the year ended December 31, 2023) (18,792 ) (38,728 ) Net Loss $ (61,319 ) $ (111,637 ) Net loss per share attributable to common stockholders-basic and diluted $ (15.96 ) $ (38.10 ) Weighted average shares of common stock outstanding-basic and diluted 3,841,405 2,929,873 Precision Biosciences, Inc. Balance Sheets Data (In thousands, except share amounts) December 31, 2023 December 31, 2022 Cash and cash equivalents $ 116,678 $ 189,576 Working capital 86,372 139,441 Total assets 159,781 238,169 Total liabilities 140,920 177,736 Total stockholders' equity $ 18,861 $ 60,433 Common stock outstanding 4,164,038 3,698,674 View source version on businesswire.com: Contacts Investor and Media Contact: Naresh Tanna Vice President, Investor Relations Naresh.Tanna@precisionbiosciences.com Source: Precision BioSciences, Inc. View this news release online at: