Perampanel

点击上方的 行舟Drug ▲ 添加关注 2020年12月31日 国家药监局药审中心关于发布《化学药品改良型新药临床试验技术指导原则》的通告（2020年第54号） 上述指导原则中明确：临床优势即患者未被满足的临床需求。在目标适应症中，对比已有的标准治疗，新药或新的治疗手段可显著提高疗效;或在不降低疗效的同时，显著降低当前用药患者的不良反应或用药的相关风险，或显著提高患者用药依从性。化药改良新药的临床优势也遵循上述原则。 而改变依从性，是目前不少改良新新药（国内和国外）的主要开发策略之一。其中，就是有不少改剂型的品种。对于改变剂型，但是未改变给药途径的改良品种，其临床的桥接研究策略该如何制定呢？ 法规依据：若改良后新药与原药品相比，PK行为发生了变化，需首先通过PK研究，探索合理的剂量与给药间隔，满足预设的临床用药要求，之后再开展随机对照临床试验验证化药改良新药至少在保持不劣于被改药品的有效性和安全性前提下，提高患者用药依从性。 笔者通过吡仑帕奈口服混悬剂以及利鲁唑口服混悬液剂两个案例，进行深入的分析，PopPK如何替代确证性临床，为同仁提供相应的研究策略和思路，打开注册思路！ PopPK在改良新药临床桥接研究专题文章: 505b2大探究：与对照制剂PK不等效，为何被FDA认为可以互换？ CDE：群体药代动力学PopPK是否可以替代确证性临床？ 在505b2大探究：与对照制剂PK不等效，为何被FDA认为可以互换？这一文章中提到：吡仑帕奈片剂（12mg）与吡仑帕奈口服混悬剂（12mg）在进食状态下的药代动力学中，AUC参数的BE标准（AUC（0-t），AUC（0-inf）和AUC（0-72h）都达到了，这表明与口服悬浮液相比，高脂肪膳食对片剂中perampanel的吸收没有影响。然而，与片剂制剂相比，单次口服12 mg悬浮液制剂的Cmax降低了约23%，Tmax中位延迟2小时。通过PopPK研究发现，单剂量评价中观察到的Cmax差异不被认为是临床差异有意义的。最终，FDA认为口服悬浮液制剂与片剂制剂相关比，具有可比性生物利用度，可互换使用。 本文将以利鲁唑口服混悬液为例，继续分析PopPK在改良型新药的临床桥接研究策略。 01 利鲁唑口服混悬液与对照片剂PK不等效 利鲁唑片（Rilutek®）是法国赛诺菲-安万特集团（Sanofi Aventis）开发的一种具有神经保护特性的谷氨酸拮抗剂，用于治疗肌萎缩侧索硬化症（ALS），延长患者生存期和气管切开的时间。利鲁唑口服混悬液（50mg/10mL）是片剂的改良剂型，本品剂型已于2018年9月在FDA以505b（2）获批。由于许多患者吞咽困难和/或需要肠内喂养，口服混悬液治疗ALS具有优势。ALS患者无法吞咽Rilutek®薄膜包衣片，目前唯一的选择是将药片压碎成粉末并溶解成液体。 利鲁唑口服混悬液/利鲁唑片的AUC0-t和AUC0-∞的几何均值比的90%CI都在80.00%-125.00%的规定范围内，表明单次给药50mg利鲁唑口服混悬液（受试制剂）和薄膜包衣片（参比制剂）后的利鲁唑吸收程度相似。受试制剂/参比制剂的Cmax的GMR的90%CI（103.28-144.88%）超出80.00-125.00%的上限，表明口服混悬液Cmax略高于片剂。 与对照片剂PK不等效，也可与原研互换使用？且看下文分解。 02 PK不等效，且看中国法规如何规定 法规要求：若改良后新药与原药品相比，PK行为发生了变化，需首先通过PK研究，探索合理的剂量与给药间隔，满足预设的临床用药要求，之后再开展随机对照临床试验验证化药改良新药至少在保持不劣于被改药品的有效性和安全性前提下，提高患者用药依从性。 解读：如果PK行为发生了变化，需要开展随机对照临床试验验证有效性和安全性。然而，这似乎与利鲁唑口服混悬液FDA上市路径以及国内获批上市路径不太相符？ 505b2大探究：利鲁唑口服混悬液临床试验设计思路。 03 PK不等效，PopPK桥接有效性 申请人共提交了三项生物等效临床研究报告和一个基于这三项研究数据的群体药代模型化分析报告。 研究1：在健康志愿者中单次给药利鲁唑50mg/10mL口服混悬液与Rilutek®50mg片剂的药代动力学比较研究（研究编号：研究CRO-PK-11-251） 研究设计：单中心、单次给药、公开标签、随机、双向交叉研究。受试者在空腹状态下，单次经口给药50mg利鲁唑受试制剂（口服混悬液）或参比制剂（薄膜包衣片），两次给药的清洗期至少5天。 试验结果：主要利鲁唑PK参数和生物等效性试验结果如下表： 研究结论：受试制剂和参比制剂在利鲁唑吸收程度方面生物等效。然而，口服混悬液的Cmax值高于片剂（GMR：122.32%），Cmax的90%CI超过现行指导原则规定的生物等效性可接受范围上限。受试制剂和参比制剂的Tmax值有显著性差异。 研究2：在健康志愿者中单次给药利鲁唑50mg/10mL口服混悬液新剂型与Rilutek®50mg片剂的生物等效性研究预试验（研究编号: 研究CRO-PK-08-213） 研究设计：单中心、单次给药、开放、随机、双向、交叉生物等效性研究预试验。根据随机分配序列，受试者在空腹状态下，单次经口给药50mg利鲁唑受试制剂（口服混悬液）或参比制剂（薄膜包衣片），两次给药间有7天的清洗期。 试验结果：主要血浆利鲁唑PK参数和统计分析结果总结在下表中： 研究结论：单次给药两种50mg利鲁唑制剂后的相对生物利用度相似，几何均值比的90%CI在现行指导原则规定的80-125%范围内。相较于片剂，混悬液的平均吸收速率更快，Tmax更早、Cmax更高。 研究3：在健康志愿者中单次给药利鲁唑50mg/10mL口服混悬液新剂型与Rilutek®50mg片剂的生物等效性研究（研究编号：研究CRO-PK-09-229） 研究设计：单中心、单剂量、开放、随机、2序列、4周期、重复两阶段、交叉设计、生物等效性研究。受试者在4个周期内，在空腹状态下，按随机分配的序列经口给药单剂量50 mg利鲁唑受试制剂（口服混悬液）或参比制剂（薄膜包衣片），每两次连续给药间的清洗期为7天。 试验结果：主要血浆利鲁唑PK参数和统计分析结果总结在下表中： 试验结论：本研究证实，受试制剂和参比制剂在利鲁唑吸收程度方面生物等效。AUC0-t和AUC0-∞几何均值比的95%CI落在80.00-125.00%的规定范围内。口服混悬液的Cmax高于片剂(GMR：116.34%)，该参数的95%CI（98.54-137.35%）超出现行指导原则规定的可接受标准上限，无法得出这两种制剂在利鲁唑吸收速率方面具有生物等效性。 研究4：利鲁唑50 mg/10 mL口服混悬液和Rilutek® 50 mg薄膜包衣片在健康志愿者中的群体药代动力学分析（研究编号：0487-2011） 研究方法：根据来自上述三项健康志愿者生物等效性研究的药代数据，建立利鲁唑混悬液和利鲁唑片剂的群体药代动力学模型，考察协变量（年龄、体重、身高、BMI、性别和种族）对药代动力学变异的影响。使用最终群体PK模型，假定每日给药两次后达到稳态，以50mg/10mL利鲁唑口服混悬液、50mg和100mg Rilutek®薄膜包衣片进行模拟。使用最终模型，对相同群体的各模拟场景生成1000条浓度曲线。此外，通过每12小时给药一次，共给药4次，来模拟各血药浓度-时间曲线，因此，计算最终模型中的CL/F和ka试验间变异性。然后，采用非房室模型计算各模拟场景下的个体PK参数。鉴于每名虚拟患者治疗4次，采用描述性统计（即，中位数、第一和第三四分位数、第5、第95和第99百分位数）计算并总结4000次Cmax和AUC0-12。 模拟情况： 所有患者给药50 mg/10 mL利鲁唑口服混悬液0、144、288和432小时的血浆浓度观测值（空心圆）。根据模型导出模拟得出的中值（实线）和90%预测区间（虚线）。起效：各给药期的个体峰浓度。 所有患者给药50mg Rilutek®薄膜包衣片0、144、288和432小时的血浆浓度观测值（空心圆）。根据模型导出模拟得出的中值（实线）和90%预测区间（虚线）。起效：各给药期的个体峰浓度。 研究结论： 使用二房室模型与顺序零级/一级吸收同时拟合受试制剂和参比制剂（不同利鲁唑制剂）。协变量分析表明，体重是CL/F和中央室和周边室容积最重要的人口统计协变量。本研究结果与文献报告的既往数据一致。 模拟稳态下，在1000名虚拟患者中连续4次给药利鲁唑（50mg口服混悬液以及50和100mg Rilutek®薄膜包衣片），结果表明50mg口服混悬液以及50mg Rilutek®薄膜包衣片的Cmax和AUC分布重叠，尽管口服混悬液的Cmax中值略高。 04 安全性无法桥接，需上市后继续完善 利鲁唑混悬液给药后的Cmax高于利鲁唑片，因此混悬液无法完全桥接来自利鲁唑片的安全性信息，而根据利鲁唑的说明书，额外增加的浓度也不会带来额外的临床获益。另外，根据申请人所做的群体PK分析，体重是模型中表观清除率和两个周围室容积的重要协变量，这说明平均体重偏小的中国患者有可能会有更高的血浆暴露。鉴于利鲁唑对肝酶的不良作用，中国患者有可能面临相对较大的肝功能损害升高风险。另外，该剂型缺少我国人群的临床安全性数据。建议收集上市后中国人群使用本品的有效性和安全性信息，并于再注册时递交。同时制定并完善上市后风险控制计划。 05 总结 （1）本品的拟用适应症为肌萎缩侧索硬化，属于临床罕见病，目前此病在我国获批的治疗仅有利鲁唑片/胶囊和依达拉奉静脉注射液，在使用上均有一定的不便性，对需要长期肠内给药且吞咽困难的患者尤其如此。因此，开发易于服用的口服混悬液剂型可满足一部分患者的临床需求。 （2）按照《境外已上市境内未上市药品临床技术要求》，本品适应症属于罕见病，本品为利鲁唑片的新剂型，对部分患者可改善服用的方便性。利鲁唑片国内外的安全性和有效性已经证实，本品如能桥接利鲁唑片临床数据，则可以豁免其境内临床试验； （3）本品递交欧盟的三项生物等效性研究（含两项预试验）结果均提示两种制剂吸收程度等效，但混悬液给药后的Cmax高于片剂的Cmax，第二个预试验和正式试验中Cmax的GMR点估计值均介于（80.00%，125.00%）之间，说明在样本量足够大的情况下，Cmax几何均值比的90%CI有可能落入预定的（80.00%，125.00%）范围内。另根据申请人提供的群体药代分析报告，预测片剂给药稳态下的Cmax范围完全包括混悬液给药的Cmax范围。 综合这些结果，基本可判断混悬液和片剂给药的药代等效，因此混悬液对ALS患者的疗效和安全性可以通过片剂的相关研究数据桥接。本品也是通过以上数据支持其在境外获得上市。 个人思考与解读 1、通过“改良型新药”吡仑帕奈口服混悬液和利鲁唑口服混液两个品种，发现口服混悬液在体内与片的PK行为有一定的差异，AUC可与对照制剂片剂等效，但是Cmax很难等效。 2、虽然国内法规要求：若改良后新药与原药品相比，PK行为发生了变化，需首先通过PK研究，探索合理的剂量与给药间隔，满足预设的临床用药要求，之后再开展随机对照临床试验验证化药改良新药至少在保持不劣于被改药品的有效性和安全性前提下，提高患者用药依从性。但是从上述案例也可以获得一些启示，PK不等效，PopPK也可桥接有效性，希望国内有越来越多的成功应用案例，提供更加多样化的临床研究策略和思路，通过PopPK豁免确证性临床。 3、当PK不等时，在使用PopPK桥接有效性和安全性时，需关注：Cmax相较于对照制剂是降低，可考虑桥接有效性和安全性，而当Cmax相较于对照制剂是偏高的，则很可能无法桥接安全性，需补充安全性相关研究。 文章信息源于公众号Susan法研社，登载该文章目的为更广泛的传递行业信息，不代表赞同其观点或对其真实性负责。文章版权归原作者及原出处所有，文章内容仅供参考。本网拥有对此声明的最终解释权，若无意侵犯版权，请联系小编删除。 学如逆水行舟，不进则退； 心似平原走马，易放难收。 行舟Drug 每日更新 欢迎订阅+ 医药大数据|行业动态|政策解读

Reports Q3 2024 Total Revenues of $128.7 Million, Representing a 25.3% YoY Increase Record Revenues Driven by Continued Organic Growth in its Rare Disease Franchise Robust Financial Performance Highlights Operational Excellence and Strong Commercial Execution FIRDAPSE® Q3 2024 Net Product Revenues of $79.3 Million, Representing a 19.7% YoY Increase AGAMREE® Q3 2024 Net Product Revenues of $15.0 Million, Demonstrating Early U.S. Launch Success FYCOMPA® Q3 2024 Net Product Revenues of $32.1 Million Q3 2024 GAAP Net Income of $43.9 Million, $0.35 Per Share Diluted Q3 2024 Non-GAAP Net Income of $71.1 Million, $0.57 Per Share Diluted Updating 2024 Full Year Total Revenue Guidance to Between $475 Million and $485 Million Conference Call and Webcast to be Held on November 7, 2024, at 8:30 AM ET CORAL GABLES, Fla., Nov. 06, 2024 (GLOBE NEWSWIRE) -- Catalyst Pharmaceuticals, Inc. (“Catalyst” or “Company”) (Nasdaq: CPRX) today reported financial results for the third quarter of 2024 and provided a corporate update. "Our strong financial performance reflects our unwavering commitment to operational and commercial excellence, driving sustained momentum and long-term growth. The early success of our newest product, AGAMREE®, along with the continued robust organic growth of our flagship product, FIRDAPSE®, highlights the strength of our U.S. commercial strategy, with revenues exceeding expectations and significantly contributing to our overall success," stated Richard J. Daly, President and CEO of Catalyst. "Through our strategic partnerships, we are advancing initiatives to expand the geographic footprint of our rare disease portfolio in key territories outside the U.S. As we pursue opportunities aligned with our long-term growth objectives and forge new partnerships to broaden our global presence, our achievements to date underscore the strength of our strategic vision to address critical unmet medical needs, driven by the outstanding execution of our teams. With a resolute focus on sustained growth and value creation, we are optimistic about the path ahead and remain confident in meeting our full-year 2024 revenue guidance, laying a strong foundation for continued success." Financial Highlights For the Three Months Ended September 30, 2024 2023 % Change(In thousands, except per share data) Product Revenue, Net$126,424$102,617 23.2% FIRDAPSE Product Revenue, Net$79,303$66,224 19.7% FYCOMPA Product Revenue, Net$32,075$36,393 (11.9%) AGAMREE Product Revenue, Net$15,046 N/A N/A GAAP Net Income (Loss)$43,884($30,764) 242.6% Non-GAAP Net Income (Loss)**$71,080($25,643) 377.2% GAAP Net Income (Loss) Per Share – Basic$0.37($0.29) 227.6% Non-GAAP Net Income (Loss) Per Share – Basic**$0.60($0.24) 350.0% GAAP Net Income (Loss) Per Share – Diluted$0.35($0.29) 220.7% Non-GAAP Net Income (Loss) Per Share – Diluted**$0.57($0.24) 337.5% As of September 30, 2024, and December 31, 2023(In thousands)Cash and Cash Equivalents$442,331$137,636 221.4% **Statements made in this press release include non-GAAP financial measures. Such information is provided as additional information and not as an alternative to Catalyst's financial statements presented in accordance with U.S. generally accepted accounting principles (“GAAP”). These non-GAAP financial measures are intended to enhance an overall understanding of Catalyst's current financial performance. Catalyst believes that the non-GAAP financial measures presented in this press release provide investors and prospective investors with an alternative method for assessing Catalyst's operating results in a manner that Catalyst believes is focused on the performance of ongoing operations and provides a more consistent basis for comparison between periods. Non-GAAP financial measures should not be considered in isolation or as a substitute for comparable GAAP accounting. Further, non-GAAP measures of net income used by Catalyst may be different from and not directly comparable to similarly titled measures used by other companies. Beginning with the third quarter of 2024, Catalyst will no longer include acquisition in-process research and development ("IPR&D") in its non-GAAP financial measures. Previously reported non-GAAP net income for the third quarter of 2023 included $81.5 million in acquisition IPR&D relating to Catalyst's acquisition, during that period, of the North American license for AGAMREE, which had not yet been approved by the U.S. Food and Drug Administration (“FDA”) at the time of the acquisition. The commercialization was subsequently approved by the FDA during the fourth quarter of 2023. Prior period amounts have been revised to conform to the current period presentation. Catalyst is making this change to its presentation following discussions with the Staff of the Division of Corporation Finance of the U.S. Securities and Exchange Commission. Recent Business Highlights Achieved total revenues of $128.7 million, including net product revenues of $126.4 million for the third quarter (“Q3”) of 2024, reflecting a 23.2% increase over net product revenues for Q3 of 2023. Reported record quarterly FIRDAPSE net product revenues of $79.3 million for Q3 2024, reflecting a 19.7% increase over Q3 2023, driven by sustained organic growth. Achieved robust AGAMREE net product revenues of $15.0 million for Q3 2024, demonstrating continued momentum in its second full quarter of U.S. commercial availability. Reported FYCOMPA® net product revenues of $32.1 million for Q3 2024, an 11.9% decrease compared to Q3 2023 revenues of $36.4 million. Announced that DyDo Pharma, Inc. (Catalyst’s sub-licensee in Japan), received regulatory approval in Japan to commercialize FIRDAPSE 10 mg tablets for the treatment of Lambert-Eaton myasthenic syndrome in Japan, marking a key milestone in expanding the product’s commercial footprint. DyDo has advised Catalyst that it expects to launch in Japan by the end of Q4 2024. Announced an exclusive agreement with KYE Pharmaceuticals, Inc. for the Canadian commercial rights to AGAMREE for Duchenne muscular dystrophy and other potential indications, further expanding Catalyst’s North American footprint. This marks the licensing of Catalyst’s second rare disease product in Canada, and KYE has advised us that it expects to file a Health Canada application for AGAMREE by early 2025. Expect total revenues for the full year 2024 to be between $475 million and $485 million, which includes the $2.1 million milestone payment received from DyDo that is included in License and other revenue. Revising full-year 2024 net product revenue guidance for FIRDAPSE to be between $300 million and $310 million; reaffirming FYCOMPA net product revenue guidance to be between $130 million and $135 million; and increasing AGAMREE net product revenue guidance to be between $40 million and $45 million, respectively. Revising full year research and development (“R&D”) expense guidance to less than $15 million due to delays in the timing of certain R&D related initiatives. Third Quarter 2024 Financial Results Total revenues: Total revenues during the third quarter of 2024 were $128.7 million, compared to $102.7 million for the third quarter of 2023, representing an increase of approximately 25.3%. Product revenue, net: Product revenue, net for the third quarter of 2024 was $126.4 million, compared to $102.6 million for the third quarter of 2023, representing an increase of approximately 23.2%. License and other revenue: License and other revenue includes $2.1 million from the arrangement with DyDo for both the three and nine months ended September 30, 2024, which consisted of a milestone payment earned upon DyDo receiving regulatory approval to commercialize FIRDAPSE for the treatment of patients with LEMS in Japan. Research and development expenses: Research and development expenses for the third quarter of 2024 were $3.3 million, compared to $83.7 million for the third quarter of 2023, representing a decrease of approximately 96.1%. Research and development expenses for the third quarter of 2023 included acquisition IPR&D of $81.5 million. Selling, general and administrative expenses: Selling, general and administrative expenses for the third quarter of 2024 were $45.9 million, compared to $33.6 million for the third quarter of 2023, representing an increase of approximately 36.7%. Amortization of intangible assets: Amortization of intangible assets was $9.3 million in the third quarter of 2024, compared to $8.5 million in the third quarter of 2023, representing an increase of approximately 10.1%. Operating income (loss): Operating income (loss) for the third quarter of 2024 was $50.9 million, compared to ($37.2) million for the third quarter of 2023, representing an increase of approximately 236.9%. GAAP net income (loss): GAAP net income (loss) for the third quarter of 2024 was $43.9 million ($0.37 per basic and $0.35 per diluted share), compared to GAAP net income (loss) of ($30.8) million (($0.29) per basic and diluted share) for the third quarter of 2023. Non-GAAP net income (loss): Non-GAAP net income (loss) for the third quarter of 2024 was $71.1 million ($0.60 per basic and $0.57 per diluted share), compared to non-GAAP net income (loss) of ($25.6) million (($0.24) per basic and diluted share) for the third quarter of 2023. Cash and cash equivalents: Cash and cash equivalents were $442.3 million as of September 30, 2024. Catalyst’s Form 10-Q for the third quarter of 2024, filed with the U.S. Securities and Exchange Commission on November 6, 2024, provides more detailed financial information and analysis of Catalyst’s financial condition and results of operations. Conference Call & Webcast DetailsThe Company will host a conference call and webcast on Thursday, November 7, 2024, at 8:30 AM ET to discuss the financial results and provide a business update. US/Canada Dial-in Number:800-715-9871International Dial-in Number:646-307-1963 A webcast will be accessible under the investor section on the Company's website at www.catalystpharma.com. A webcast replay will be available on the Catalyst website for 30 days after the event. About Catalyst Pharmaceuticals Catalyst Pharmaceuticals, Inc. (Nasdaq: CPRX) is a biopharmaceutical company committed to improving the lives of patients with rare diseases. With a proven track record of bringing life-changing treatments to the market, Catalyst’s focus is on in-licensing, commercializing, and developing innovative therapies. Guided by its deep commitment to patient care, Catalyst prioritizes accessibility, ensuring patients receive the care they need through a comprehensive suite of support services designed to provide seamless access and ongoing assistance. Catalyst maintains a well-established U.S. presence while actively seeking to expand its global commercial footprint through strategic partnerships. Catalyst is headquartered in Coral Gables, FL., and was recognized on the Forbes 2024 list as one of America's most successful small-cap companies. For more information, please visit Catalyst's website at www.catalystpharma.com. Forward-Looking StatementsThis press release contains forward-looking statements. Forward-looking statements involve known and unknown risks and uncertainties, which may cause Catalyst's actual results in future periods to differ materially from forecasted results. A number of factors, including (i) whether the launch of AGAMREE® will continue to surpass initial expectations and exceed 2024 full-year revenue forecasts for sales of the product that have been published by the Company, (ii) whether AGAMREE's commercialization will ultimately be profitable, cash flow positive, and accretive to Catalyst, (iii) Catalyst's ability to continue to successfully sell its current products and continue to be profitable and cash flow positive, (iv) whether Catalyst's total revenue forecast for 2024 that is included in this press release will prove to be accurate, (v) whether Catalyst will complete additional acquisitions of products, and the timing of any such acquisitions, (vi) the impact of pending Paragraph IV litigation relating to FIRDAPSE® if the results of these litigation matters are adverse, (vii) whether AGAMREE will be approved for commercialization in Canada, (viii) whether DyDo can successfully commercialize FIRDAPSE in Japan, and (ix) those factors described in Catalyst's Annual Report on Form 10-K for the 2023 fiscal year, Catalyst's Quarterly Report on Form 10-Q for the third quarter of 2024, and Catalyst's other filings with the SEC, could adversely affect Catalyst. Copies of Catalyst's filings with the SEC are available from the SEC and may be found on Catalyst's website or obtained upon request from Catalyst. Catalyst does not undertake any obligation to update the information contained herein, which speaks only as of this date. CATALYST PHARMACEUTICALS, INC.CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited)(in thousands, except share and per share data) For the Three MonthsEnded September 30, For the Nine MonthsEnded September 30, 2024 2023 2024 2023Product revenue, net$126,424 $102,617 $347,518 $287,398License and other revenue 2,271 71 2,396 238Total revenues 128,695 102,688 349,914 287,636 Operating costs and expenses: Cost of sales (a) 19,277 14,167 47,202 36,158Research and development 3,284 83,662 8,850 91,178Selling, general and administrative (a) 45,880 33,560 133,548 91,674Amortization of intangible assets 9,345 8,487 28,033 23,506Total operating costs and expenses 77,786 139,876 217,633 242,516Operating income (loss) 50,909 (37,188) 132,281 45,120Other income (expense), net 6,296 (833) 9,801 2,684Net income (loss) before income taxes 57,205 (38,021) 142,082 47,804Income tax provision (benefit) 13,321 (7,257) 34,129 11,238Net income (loss)$43,884 $(30,764) $107,953 $36,566 Net income (loss) per share: Basic$0.37 $(0.29) $0.92 $0.34Diluted$0.35 $(0.29) $0.87 $0.32 Weighted average shares outstanding: Basic 118,931,153 106,568,137 117,976,056 106,133,077Diluted 125,407,279 106,568,137 124,519,838 113,751,370 (a) exclusive of amortization of intangible assets CATALYST PHARMACEUTICALS, INC.RECONCILIATION OF NON-GAAP METRICS (unaudited)(in thousands, except share and per share data) For the Three MonthsEnded September 30, For the Nine MonthsEnded September 30, 2024 2023 2024 2023GAAP net income (loss)$43,884 $(30,764) $107,953 $36,566Non-GAAP adjustments: Stock-based compensation expense 4,424 3,810 17,080 10,000Depreciation 106 81 283 232Amortization of intangible assets 9,345 8,487 28,033 23,506Income tax provision (benefit) 13,321 (7,257) 34,129 11,238Non-GAAP net income (loss)$71,080 $(25,643) $187,478 $81,542 Non-GAAP net income (loss) per share: Basic$0.60 $(0.24) $1.59 $0.77 Diluted$0.57 $(0.24) $1.51 $0.72 Weighted average shares outstanding: Basic 118,931,153 106,568,137 117,976,056 106,133,077 Diluted 125,407,279 106,568,137 124,519,838 113,751,370 CATALYST PHARMACEUTICALS, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands) September 30,2024(unaudited) December 31,2023Assets Current Assets: Cash and cash equivalents$442,331 $137,636Accounts receivable, net 58,266 53,514Inventory 20,017 15,644Prepaid expenses and other current assets 18,384 12,535Total current assets 538,998 219,329Operating lease right-of-use asset, net 2,301 2,508Property and equipment, net 1,380 1,195License and acquired intangibles, net 166,016 194,049Deferred tax assets, net 48,473 36,544Investment in equity securities 14,842 16,489Total assets$772,010 $470,114 Liabilities and Stockholders’ Equity Current Liabilities: Accounts payable$11,563 $14,795Accrued expenses and other liabilities 93,832 61,268Total current liabilities 105,395 76,063Operating lease liability, net of current portion 2,889 3,188Other non-current liabilities 2,785 2,982Total liabilities 111,069 82,233Total stockholders’ equity 660,941 387,881Total liabilities and stockholders’ equity$772,010 $470,114 Source: Catalyst Pharmaceuticals, Inc. Contact information: Investor ContactMary ColemanCatalyst Pharmaceuticals, Inc.(305) 420-3200mcoleman@catalystpharma.com Media ContactDavid SchullRusso Partners(858) 717-2310david.schull@russopartnersllc.com