Dextroamphetamine

Phase 3 Data Collected to Date Sufficient for Submission of New Drug Application CTx-1301 Could Benefit >60% of ADHD Patients Currently Using Immediate-Release Booster Doses Advancing Discussions with Commercialization Partners Ready to Engage with Payers for Reimbursement and Market Access KANSAS CITY, Kan., May 21, 2024 (GLOBE NEWSWIRE) -- Cingulate Inc. (NASDAQ: CING), a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, announced that it has received confirmation from and is aligned with the U.S. Food and Drug Administration (FDA) on the requirements necessary for filing a New Drug Application (NDA) for its lead Phase 3 candidate CTx-1301 (dexmethylphenidate), for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients six years of age or older. Details from the FDA communication to Cingulate include the following: Per the 505(b)(2) pathway, submission of CTx-1301’s NDA does not require continuation of the fixed dose study and the onset and duration study; Data collected to date from these two Phase 3 studies will be included in the filing; and Contemporaneously with the preparation of the NDA filing, Cingulate will conduct a Phase 1 fed/fast study, the study is expected to last approximately two to three weeks, with the results being included in the NDA filing. “We are pleased with the FDA’s guidance and perspective regarding our pathway to a timely NDA filing, and we will proceed to complete all remaining requirements accordingly,” said Cingulate Chairman and CEO Shane J. Schaffer. “We also believe this communication provides additional go-to-market momentum as we continue to meet with potential partners for the outlicensing of CTx-1301 in the United States and abroad. Now that we have a clear path to submission, we look forward to engaging with key payer stakeholders to achieve maximum access and market penetration to benefit ADHD patients and their families.” Cingulate has begun NDA preparation and expects to submit its filing in the first half of 2025. Ann Childress, M.D., President, Center for Psychiatry and Behavior Medicine, Inc., and lead investigator of Cingulate’s CTx-1301 onset and duration study, stated, “The treatment effect size of CTx-1301 was remarkable given the current effect sizes observed in the marketplace. Many patients require longer duration of efficacy and must add a second, or booster, dose to ensure treatment effect over their entire active day. The patients I observed, once notified they were taking CTx-1301, have expressed a desire to remain on the medication after the trial concluded.” “If approved,” Childress continued, “I believe CTx-1301 could potentially benefit the more than 60 percent of patients currently using immediate-release booster doses to extend the efficacy of their medications.” Earlier this year, Cingulate presented results from the Phase 3 adult efficacy and safety study of CTx-1301 at the 2024 American Professional Society of ADHD and Related Disorders (APSARD) conference in Orlando, FL. The results were previously presented at the 2023 Psych Congress, where a poster describing the data was selected as a finalist for the Psych Congress’s First Annual Poster Awards. The Cingulate poster presented at APSARD provided additional insight regarding CTx-1301’s ADHD leading effect size. Effect size conveys clinical significance rather than statistical significance, is not reliant on sample size, and allows for comparison across trials. The poster presented may be viewed here. About Attention Deficit/Hyperactivity Disorder (ADHD) ADHD is a chronic neurobiological and developmental disorder that affects millions of children and often continues into adulthood. The condition is marked by an ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development. In the U.S., approximately 6.4 million children and adolescents (11 percent) aged under the age of 18 have been diagnosed with ADHD. Among this group, approximately 80 percent receive treatment, with 65-90 percent demonstrating clinical ADHD symptoms that persist into adulthood. Adult ADHD prevalence is estimated at approximately 11 million patients (4.4 percent), almost double the size of the child and adolescent segment combined. However, only an estimated 20 percent receive treatment. About CTx-1301 Cingulate’s lead candidate, CTx-1301, utilizes Cingulate’s proprietary PTR drug delivery platform to create a breakthrough, multi-core formulation of the active pharmaceutical ingredient dexmethylphenidate, a compound approved by the FDA for the treatment of ADHD. Dexmethylphenidate is part of the stimulant class of medicines and increases norepinephrine and dopamine activity in the brain to affect attention and behavior. While stimulants are the gold standard of ADHD treatment due to their efficacy and safety, the long-standing challenge continues to be providing patients with an entire active-day duration of action. CTx-1301 is designed to precisely deliver three releases of medication at the predefined time, ratio, and style of release to optimize patient care in one tablet. The result is a rapid onset and entire active-day efficacy, with the third dose being released around the time when other extended-release stimulant products begin to wear off. About Precision Timed Release™ (PTR™) Platform Technology Cingulate is developing ADHD and anxiety disorder product candidates capable of achieving true once-daily dosing using Cingulate’s innovative PTR drug delivery platform technology. It incorporates a proprietary Erosion Barrier Layer (EBL) providing control of drug release at precise, pre-defined times with no release of drug prior to the intended release. The EBL technology is enrobed around a drug-containing core to give a tablet-in-tablet dose form. It is designed to erode at a controlled rate until eventually the drug is released from the core tablet. The EBL formulation, Oralogik™, is licensed from BDD Pharma. Cingulate intends to utilize its PTR technology to expand and augment its clinical-stage pipeline by identifying and developing additional product candidates in other therapeutic areas in addition to Anxiety and ADHD where one or more active pharmaceutical ingredients need to be delivered several times a day at specific, predefined time intervals and released in a manner that would offer significant improvement over existing therapies. To see Cingulate’s PTR Platform, click here. About Cingulate® Cingulate Inc. (NASDAQ: CING), is a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, designed to improve the lives of patients suffering from frequently diagnosed conditions characterized by burdensome daily dosing regimens and suboptimal treatment outcomes. With an initial focus on the treatment of attention deficit/hyperactivity disorder (ADHD), Cingulate is identifying and evaluating additional therapeutic areas where PTR technology may be employed to develop future product candidates, including to treat anxiety disorders. Cingulate is headquartered in Kansas City. For more information visit Cingulate.com. Forward-Looking Statements 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. These forward-looking statements include all statements, other than statements of historical fact, regarding our current views and assumptions with respect to future events regarding our business, including statements with respect to our plans, assumptions, expectations, beliefs and objectives with respect to product development, clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. These statements are generally identified by the use of such words as “may,” “could,” “should,” “would,” “believe,” “anticipate,” “forecast,” “estimate,” “expect,” “intend,” “plan,” “continue,” “outlook,” “will,” “potential” and similar statements of a future or forward-looking nature. Readers are cautioned that any forward-looking information provided by us or on our behalf is not a guarantee of future performance. Actual results may differ materially from those contained in these forward-looking statements as a result of various factors disclosed in our filings with the Securities and Exchange Commission (SEC), including the “Risk Factors” section of our Annual Report on Form 10-K filed with the SEC on April 1, 2024. All forward-looking statements speak only as of the date on which they are made, and we undertake no duty to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law. Investor Relations Thomas Dalton Vice President, Investor & Public Relations, Cingulate TDalton@cingulate.com 913-942-2301 Matt Kreps Darrow Associates mkreps@darrowir.com 214-597-8200 A photo accompanying this announcement is available at Cingulate's Precision Timed Release Technology™ (PTR™) Platform Technology Cingulate® is developing ADHD product candidates capable of achieving true once-daily dosing using the Company’s innovative Precision Timed Release™ (PTR™) drug delivery platform technology incorporating a proprietary Erosion Barrier Layer (EBL) that provides control of drug release at precise, pre-defined times with no release of drug prior to the intended release.The technology is an erodible barrier layer that is wrapped around a drug containing core to give a tablet-in-tablet dose form. The barrier layer is designed to erode at a controlled rate until eventually the drug is released from the core tablet.CTx-1301 (dexmethylphenidate) and CTx-1302 (dextroamphetamine) have pioneering compression technology with specialized release characteristics that may enable patients to take one tablet per day and avoid the use of additional immediate release “boosters.”We believe our most advanced drug product candidate, CTx-1301, will be the first true once-daily dexmethylphenidate tablet

这项研究表明，ADHD药物治疗与卒中、心力衰竭和复合结局的10年标准化风险升高有关，并且，每日服用＞1 DDD的患者10年标准化风险可能具有剂量反应关系。 丹麦哥本哈根大学医院的研究团队利用丹麦国家健康登记处的数据，开展了一项观察性研究，分析了ADHD药物与急性冠脉综合征、卒中和心力衰竭的长期风险的关联。他们发现，与既往服药者相比，当前每日接受≥1规定每日剂量ADHD药物者的卒中、心力衰竭和复合心血管结局风险分别增加20%、70%和30%。 研究结果发表在《美国心脏病学会杂志》上[1]。 研究使用了丹麦国家健康登记处的数据，具有良好的代表性。研究纳入了1998-2020年间所有接受首次接受ADHD药物治疗的成年人，使用的药物包括哌甲酯、托莫西汀、利右苯丙胺、右苯丙胺和莫达非尼，并且排除了患多发性硬化症、发作性睡病患者和超适应证的姑息治疗（因癌症接受阿片类药物治疗）患者。 研究人员共确认了73264名成年ADHD患者，基线时，26357人（36%）停止治疗，被划分为既往服药组，平均年龄30岁，其余正在接受治疗的患者按照服药剂量分为低剂量组（＜1规定每日剂量[DDD]）和高剂量组（≥1 DDD），分别有31211人（43%）和15696人（21%），平均年龄分别为31岁和33岁。他们还创建了一个包含145456名未患ADHD和未接受ADHD药物治疗的匹配对照组。 参与者最长接受10年的随访，中位为6.5年。随访期间，低剂量组和高剂量组分别发生了187例和159例急性冠脉综合征，345例和159例卒中，167例和87例心力衰竭，相应的，匹配对照组和既往服药组的三种心血管疾病的发生数量分别为646例和169例，1031例和326例，579例和140例。 研究人员据此计算了10年内，每一组参与者每年每种疾病的标准化绝对风险。 10年内的匹配对照（蓝）、既往使用（橙）、低剂量（黑）和高剂量组（紫）的急性冠脉综合征、卒中、心力衰竭和复合结局在10年内每年的标准化疾病风险 基于10年标准化绝对风险，研究人员以既往服药组为对照计算了其他组的相对风险，他们发现，高剂量组与卒中风险增加20%、心力衰竭风险增加70%和包含急性冠脉综合征、卒中和心力衰竭的复合结局风险增加30%有关，但与急性冠脉综合征风险无关。 匹配对照（蓝）、既往使用（橙）、低剂量（黑）和高剂量组（紫）的急性冠脉综合征、卒中、心力衰竭和复合结局的10年标准化绝对风险和相对风险 与匹配对照组相比，低剂量组和高剂量组均与心血管疾病的10年标准化绝对风险增加有关，复合结局风险分别增加40%和70%。 补充分析显示，根据性别、年龄和伴随治疗分组的亚组分析显示出了相似的风险关联。40岁以上和伴随精神疾病药物或非甾体抗炎药物治疗的参与者有最高的卒中、心力衰竭和复合结局10年标准化风险。 综上，这项研究表明，ADHD药物治疗与卒中、心力衰竭和复合结局的10年标准化风险升高有关，并且，每日服用＞1 DDD的患者10年标准化风险可能具有剂量反应关系。 在同期发表的评论文章中[2]，评论人员肯定了研究的价值，同时也指出，研究的几点局限性需要注意，例如，ADHD本身也与心血管疾病风险增加有关，因此与其他非随机的流行病学研究一样，存在疾病本身的混淆风险，高剂量的治疗可能意味着更严重的ADHD或其他与心血管风险增加独立相关的疾病。 另外，参与者中有较高比例同时服用其他精神疾病药物，如18.6%同时服用抗精神疾病药物，34.9%同时服药抗抑郁药物，这些患者的主要疾病是否有可能是抑郁症、焦虑症或其他精神疾病，而非ADHD？同样，非甾体抗炎药物也与心血管疾病风险增加有关，同时服用的参与者在高剂量组更为普遍。 研究人员指出，在年轻的ADHD患者中，长期服用ADHD药物与心血管疾病的潜在联系应该受到精神科医生的重视，他们希望这项研究和其他观察性研究的发现能够启发未来的临床研究。 参考文献： [1] Holt A, Strange J E, Rasmussen P V, et al. Long-term cardiovascular risk associated with treatment of attention-deficit/hyperactivity disorder in adults[J]. Journal of the American College of Cardiology, 2024, 83(19): 1870-1882. [2] Alexander G C, Moore T J, Brass E P. Long-Term Cardiovascular Risks of Psychostimulant Drugs for Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD)[J]. Journal of the American College of Cardiology, 2024, 83(19): 1883-1885.