Irinotecan Hydrochloride

First patient dosed in Phase 2 clinical trial with NGC-Cap for metastatic breast cancer Positive data from preclinical studies support NGC-Iri’s ability to deliver more SN-38 to tumors compared with either irinotecan or Onivyde® HANOVER, Md., Oct. 30, 2024 (GLOBE NEWSWIRE) -- Processa Pharmaceuticals, Inc. (Nasdaq: PCSA) (Processa or the Company), a clinical-stage pharmaceutical company focused on developing the next generation of chemotherapeutic drugs with improved efficacy and safety, provides updates on its product pipeline, upcoming milestones and business activities, and reports financial results for the three and nine months ended September 30, 2024. “We continued to make progress with our programs as we further demonstrate the potential benefits of our oncology therapeutics,” said George Ng, Chief Executive Officer of Processa Pharmaceuticals. “Our NGC-Cap Phase 2 clinical trial in metastatic breast cancer is underway with the first patient dosed. As this is an open-label trial, we anticipate sharing initial data in the second half of 2025. Additionally, we reported positive findings from preclinical studies that support NGC-Iri’s potential for improved efficacy and a superior side effect profile compared with the commonly used FDA-approved chemotherapy drugs irinotecan and Onivyde®. We are pleased with our progress and remain committed to improving the lives of people with cancer.” Key Program UpdatesProcessa is focused on developing next-generation chemotherapies (NGC) by improving widely used U.S. Food and Drug Administration (FDA)-approved drugs to extend cancer patients’ survival and/or improve their quality of life. This is achieved by altering how drugs are metabolized and/or distributed in the body, including how they reach cancer cells. In addition, Processa utilizes its Regulatory Science Approach, including the principles associated with FDA’s Project Optimus Oncology initiative, in the development of its NGC drug products to achieve a more favorable benefit-risk profile. PCS6422: Next-Generation Capecitabine (NGC-Cap) NGC-Cap is a combination of PCS6422 and capecitabine, which is the oral prodrug of the cancer drug 5-fluorouracil (5-FU). PCS6422 alters the metabolism of 5-FU, resulting in more 5-FU distributed to cancer cells.Earlier this month, the first patient was dosed in a Phase 2 clinical trial (NCT06568692) evaluating NGC-Cap for the treatment of advanced or metastatic breast cancer. The Phase 2 study is a global, multicenter, open-label, adaptive-design trial comparing two different doses of NGC-Cap to FDA-approved monotherapy capecitabine in approximately 60 to 90 patients. The trial is designed to evaluate the safety-efficacy profile of NGC-Cap versus monotherapy capecitabine, to determine the potential optimal dosage regimens of NGC-Cap as required by the FDA Project Optimus Initiative and to evaluate the possibility of personalizing NGC-Cap therapy. The Company expects to announce interim data from this trial in the second half of 2025. PCS3117: Next-Generation Gemcitabine (NGC-Gem) NGC-Gem is an oral analog of gemcitabine (Gemzar®) that is converted to its active metabolite by a different enzyme system, with potential for a positive response in gemcitabine patients including those inherently resistant to or who acquire resistance to gemcitabine.Processa is evaluating the potential of NGC-Gem in patients with pancreatic and other cancers, as well as ways to identify patients who are more likely to respond to NGC-Gem than gemcitabine alone. The Company is requesting a meeting with the FDA to discuss potential trial designs, including implementation of the Project Optimus initiative. PCS11T: Next-Generation Irinotecan (NGC-Iri) NGC-Iri is an analog of SN-38, the active metabolite of irinotecan, that is expected to have an improved safety-efficacy profile in every type of cancer where irinotecan is currently used.As announced in August, two studies in a human melanoma xenograft mouse model measured SN-38 in tumors, plasma and other tissues following administration of NGC-Iri, irinotecan and Onivyde®, the liposomal formulation of irinotecan. One study compared NGC-Iri with irinotecan, and the other compared irinotecan with Onivyde®. The results found that mice administered NGC-Iri had greater accumulation of SN-38 in the tumor compared with other tissues and that less SN-38 accumulated in non-cancer tissues, which could lead to improved efficacy with a more favorable adverse event profile compared with irinotecan and Onivyde®.The Company is currently evaluating the manufacturing process and potential sites for NGC-Iri. In addition, Processa is defining the potential paths to approval, which includes defining the target patient population and the type of cancer, and expects to conduct IND-enabling toxicology studies in 2025. Third Quarter Financial Results Research and development expenses for the third quarter of 2024 were $2.3 million, compared with $1.2 million for the third quarter of 2023. General and administrative expenses for the third quarter of 2024 were $1.1 million, compared with $1.0 million for the third quarter of 2023. The net loss for the third quarter of 2024 was $3.4 million, or $1.03 per share, compared with the net loss for the third quarter of 2023 of $2.1 million, or $1.54 per share. All per-share figures reflect a 1-for-20 reverse stock split that was effective as of January 22, 2024. Cash and cash equivalents were $2.9 million as of September 30, 2024. About Processa Pharmaceuticals, Inc. Processa is a clinical-stage pharmaceutical company focused on developing the Next Generation Chemotherapy (NGC) drugs with improved safety and efficacy. Processa’s NGC drugs are modifications of existing FDA-approved oncology therapies resulting in an alteration of the metabolism and/or distribution of these drugs while maintaining the existing mechanisms of killing the cancer cells. By combining its novel oncology pipeline with proven cancer-killing active molecules and its Regulatory Science Approach, Processa’s strategy is to develop more effective therapy options with improved tolerability for cancer patients through an efficient regulatory path. For more information, visit our website at www.processapharma.com. Forward-Looking Statements This release contains forward-looking statements. The statements in this press release that are not purely historical are forward-looking statements which involve risks and uncertainties. Actual future performance outcomes and results may differ materially from those expressed in forward-looking statements. Please refer to the documents filed by Processa Pharmaceuticals with the SEC, specifically the most recent reports on Forms 10-K and 10-Q, which identify important risk factors which could cause actual results to differ from those contained in the forward-looking statements. Company Contact:Patrick Lin(925) 683-3218plin@processapharma.com Investor Relations Contact:Yvonne BriggsAlliance Advisors Investor Relations(310) 691-7100ybriggs@allianceadvisorsir.com [Financial Tables to follow]PROCESSA PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands, except share information) (unaudited) September 30, 2024 December 31, 2023 ASSETS Current Assets Cash and cash equivalents $2,891 $4,706 Prepaid expenses and other 1,947 926 Total Current Assets 4,838 5,632 Property and Equipment, net 5 3 Other Assets Lease right-of-use assets, net of accumulated amortization 93 146 Security deposit 6 6 Total Other Assets 99 152 Total Assets $4,942 $5,787 LIABILITIES AND STOCKHOLDERS’ EQUITY Current Liabilities Current maturities of lease liabilities $94 $84 Accounts payable 712 312 Due to licensor - 189 Due to related parties - - Accrued expenses 413 146 Total Current Liabilities 1,219 731 Non-current Liabilities Non-current lease liabilities 2 67 Total Liabilities 1,221 798 Commitments and Contingencies - - Stockholders’ Equity Common stock, par value $0.0001, 100,000,000 shares authorized: 3,271,944 issued and 3,266,944 outstanding at September 30, 2024; and 1,291,000 issued and 1,286,000 outstanding at December 31, 2023 - - Additional paid-in capital 88,511 80,658 Treasury stock at cost — 5,000 shares at September 30, 2024 and December 31, 2023 (300) (300)Accumulated deficit (84,490) (75,369)Total Stockholders’ Equity 3,721 4,989 Total Liabilities and Stockholders’ Equity $4,942 $5,787 PROCESSA PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except per share data)(unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Operating Expenses Research and development $2,288 $1,152 $5,557 $4,479 General and administrative 1,137 1,016 3,760 4,509 Operating Loss (3,425) (2,168) (9,317) (8,988) Other Income (Expense) Interest income, net 40 86 195 271 Net Loss $(3,385) $(2,082) $(9,122) $(8,717) Net Loss per Common Share - Basic and Diluted $(1.03) $(1.54) $(3.13) $(6.81) Weighted Average Common Shares Used to Compute Net Loss Applicable to Common Shares - Basic and Diluted 3,275,998 1,350,188 2,909,941 1,279,298 # # #

编者按：神经内分泌癌(NEC)罕见的发病率、高度侵袭性及其复杂的临床表现为其治疗带来了巨大挑战，肺是NEC最常见的原发部位。晚期肺NEC治疗选择局限，本期“例例生辉”，天津市肿瘤医院医院的姜战胜教授将为我们分享一例初诊的ⅢA期肺高级别NEC常规序贯放化疗后出现进展的患者。该患者在后续使用恩沃利单抗联合靶向及化疗4周期治疗后即出现了胸水吸收，多发淋巴结缩小，达到了部分缓解（PR）的临床疗效评价。目前患者仍在这一治疗方案中持续获益。让我们一睹为快！ 研究背景 近年来，肺癌诊疗领域进展突飞猛进，但肺NEC的整体生存状况仍待改善。肺NEC包括小细胞肺癌（SCLC）及肺大细胞神经内分泌癌（LCNEC），由于其高侵袭性和治疗应答的异质性，患者在治疗选择和预后方面仍面临重大挑战，因此亟需进一步的研究和创新疗法来改善临床结局。 III期无法切除的LCNEC，推荐化疗＋放疗联合治疗。一项纳入5797例局部晚期LCNEC患者的回顾性研究显示，根治性同步放化疗较单纯化疗疗效更佳（mOS：16.1 vs 11.9月）[1]。这一结论在其他大型回顾性研究中也得到验证。基于有限的数据，可认为含4周期EP方案（依托泊苷+顺铂）的同步放化疗，是不可切除III期LCNEC合理的选择[2]。 程序性死亡受体1(PD-1)/程序性死亡受体配体1(PD-L1)抑制剂已被美国食品药品监督管理局和国家药品监督管理局批准用于多个瘤种的广泛治疗，为治疗难治性和复发性肺癌带来了新的希望。恩沃利单抗是全球首个通过皮下注射给药途径的特异性阻断PD-L1的药物，其他已获批的PD-1/PD-L1抗体均为静脉输注给药。2021年，恩沃利单抗在中国获批用于治疗不可切除或转移性微卫星高度不稳定(MSI-H)或错配修复缺陷(dMMR)的晚期实体瘤[3]。2022年CSCO大会报告了一项探索恩沃利单抗联合卡铂/顺铂和依托泊苷一线治疗广泛期小细胞肺癌(ES-SCLC)的II期临床研究[4] ,该研究中有14例(87.5% )达到部分缓解(PR) ，2例(12. 5%)疾病稳定(SD) ,客观缓解率（ORR）为87.5%,疾病控制率(DCR)高达100%，表明免疫联合化疗可为ES-SCLC患者带来临床获益。但免疫治疗在LCNEC的应用价值仍需要探索。本期通过详细描述恩沃利单抗联合治疗方案在一例(右肺)高级别神经内分泌癌患者中的应用，为免疫治疗在LCNEC&SCLC患者中的治疗价值进行了一次积极探索。具体内容如下： 病例报告 患者信息 基本信息：患者男性，71岁。 主诉：确诊右肺癌5天。 既往史、家族史：无特殊。 个人史：吸烟史40年，25支/天。无饮酒不良嗜好。 辅助检查 强化CT：提示右肺上叶肿物，考虑肺癌可能性大；纵隔淋巴结肿大；支气管炎，双肺肺气肿。 PET-CT：右肺上叶肿物向右主支气管延伸，大小约1.8x6.9x5.9cm，符合中心型肺癌伴阻塞性炎症；右肺门及双颈等多处结节，考虑淋巴结转移或增生反应，最大结节约1.6x1.1cm。 头部强化MRI：左侧小脑半球异常信号，不除外微小转移。 病理检查：右肺上叶活检结果为癌，形态及免疫组化倾向于高级别神经内分泌癌，小部分倾向小细胞，神经内分泌指标表达欠佳。 基因检测：RB1基因p.P6Rfs*2122.44%；TP53基因p.R249S 45.97%；PIK3CA基因拷贝扩增3.4；MSS。 诊断结果 T3N1M0 IIIA期（局限期）右肺癌，右肺门淋巴结转移。分子分型：RB1、TP53突变及PIK3CA扩增；MSS；PDL1（TPS<1%）。ECOG评分：1分。 治疗经过 图1 治疗流程图 2023年7月：患者接受3周期EP化疗（依托泊苷180mg d1-3，顺铂60mg d1-2）3周期后，复查CT显示右肺上叶支气管开口周围肿物较前缩小（6.9×5.9cm至6.8×4.1cm），疾病稳定（图2）。 图2 化疗3周期后影像学评估疗效 2023年10月：患者接受放疗，放疗计划为PTV54Gy/3Gy/18f。放疗1月后复查CT显示：与2023-9-15相比，右肺上叶及右主支气管内肿物增大（6.8x4.1cm到7.2x4.2cm），周围结节增多，支气管狭窄加重；左肺下叶透亮影壁厚减轻，粟粒增多；纵隔及右肺淋巴结无显著变化（较大者短径约1.1cm），提示病情稳定（图3）。  图3 放疗1月后影像学疗效评估 2023年12月22日CT表现考虑为放射性肺炎，不排除合并细菌感染。患者未再入院行抗肿瘤治疗，于当地医院口服激素治疗，具体剂不详（图4）。 图4 放疗2月后影像学考虑放射性肺炎 2023年12月22日患者于当地医院复查CT提示病灶较前缩小，疗效评价PR（图5）。 图5 放疗2月后影像学疗效评估 2024年2月3日患者于当地医院复查CT提示疗效维持PR（肿物大小4.0x4.3cm）（图6）。 图6放疗4月后影像学疗效评估 患者2024年4月活动后喘憋，2024年4月11日，患者于我院检查CT结果显示：与2023年11月14日相比，右肺上叶及右主支气管肿物缩小，但右肺上叶支气管闭塞，出现肺不张和中下叶实变；双肺胸膜下多发结节及浸润影，考虑炎性改变；纵隔淋巴结增大（最大短径约1.4cm），右侧胸腔有少量积液。与当地医院2024年2月3日CT相比肿物较前明显增大，以上提示疾病进展（图7）。  图7 放疗6月后影像学疗效评估 由于患者疾病进展，因此改变患者治疗方案，2024年4月11日开始接受免疫联合靶向联合化疗2周期，方案为恩沃利单抗300mg d1，安罗替尼10mg d1-14，依托泊苷胶囊50mg d1-10（周期1）/100mg d1-7（周期2）。治疗2周期后，CT显示右肺上叶肿物缩小（约5.3x4.5cm），右肺上叶复张，中下叶实变部分吸收；左肺上叶胸膜下结节缩小，新见斜裂旁及舌段结节，建议抗炎后复查；纵隔及右肺门淋巴结缩小（最大短径约0.9cm），右侧胸腔积液吸收，其余无显著变化（图8）。 图8 免疫联合靶向治疗及化疗2周期后影像学疗效评估 2024年7月患者继续免疫联合靶向联合化疗2周期，方案为恩沃利单抗300mg d1，安罗替尼10mg d1-14，依托泊苷胶囊100mg d1-7。2024年8月6日患者复查CT示：右肺上叶肿物较前缩小（范围4.2x3.9cm），提示病情稳定，疗效评价PR（图9）。 图9 免疫联合靶向治疗及化疗2周期后影像学疗效评估 研究结论 本病例报告了一例(右肺)高级别神经内分泌癌IIIA期患者在接受了3周期化疗，18次放疗，病情进展之后接受了4周期的恩沃利单抗联合靶向和化疗。在4周期治疗之后，患者右肺肿物缩小，胸水吸收，右肺复张，疗效评估达到部分缓解（PR）。提示恩沃利单抗是肺NEC患者的有效治疗选择。当然，我们需要更多的临床试验数据，来进一步支持恩沃利单抗的治疗潜力，为局部晚期的肺NEC患者提供更多的治疗策略。 专家点评 相较于非小细胞肺癌（NSCLC），肺NEC发病率低，但基于肺癌庞大的发病率，这部分患者人数不容忽视。同时，随着病理诊断手段及水平的不断上升，肺NENs的发病率也逐渐上升[5]。近年来，精准医疗改变了癌症的诊疗方案，尤其在NSCLC领域得到了突飞猛进的发展。肺NEC这种相对罕见的肿瘤，也在免疫治疗中迎来曙光。 恩沃利单抗是全球首个可以皮下给药的PD-L1单抗药物，通过抑制肿瘤免疫逃逸机制，激活免疫系统，已经在晚期实体瘤中展现出初步的抗肿瘤疗效[6-7]。WCLC大会公布了一项前瞻性、单臂、I期研究，纳入32例既往未经治疗的广泛期小细胞肺癌（ES-SCLC）患者，接受四个周期的卡铂(AUC=5/6，D1)和依托泊苷(80-100 mg/m2，D1-3)联合恩沃利单抗(300mg，D6)的诱导治疗，随后进行恩沃利单抗300 mg维持治疗，直至出现进展或无法耐受的毒性。中位随访时间为10.6个月(95%C1,8.8-12.8)，中位PFS为6.2个月，中位OS未达到。6个月和12个月PFS率分别为52.3%和14.0%，6个月、9个月和12个月OS率分别为87.3%，79.6%和71.9%，疗效显著[8]。 恩沃利单抗在晚期实体瘤二线治疗中也展示出了潜力，在CSCO指南中被推荐用于MSI-H/dMMR的胃癌、子宫内膜癌患者的二线治疗[9-10]。CN-006研究是恩沃利单抗单药治疗二线及以上MSI-H/ dMMR实体瘤的单臂、国内多中心II期研究，结果显示，恩沃利单抗单药治疗既往接受至少一线标准治疗失败的 MSI-H/ dMMR 晚期CRC患者中疗效显著[11-12]。本例患者经过一线方案治疗，无进展生存期（PFS）达到了8.5个月，之后出现疾病进展，二线使用恩沃利单抗+安罗替尼+依托泊苷治疗，最终达到部分缓解。体现出恩沃利单抗在晚期肺神经内分泌癌二线治疗中的优势。未来期待恩沃利单抗能为更多患者带来新的选择和希望。 专家简介 姜战胜 天津市肿瘤医院 中西医结合科 副主任医师 医学博士、硕士生导师 天津市抗癌协会中西医结合肿瘤治疗专业委员会 候任主委 承担多项国家级、省部级课题 发表中英学术论文数十篇，拥有发明专利两项、实用专利两项 医生简介 张曼 天津市肿瘤医院空港医院  中西医结合科 主治医师 医学博士 中国抗癌协会乳腺癌专业委员会会员 主要从事肿瘤内科临床工作 发表多篇论文 主持天津市滨海新区卫健委科技项目课题1项 仅供医疗卫生专业人士阅读 转载自：SIMMED 恩维达学术进展：1、2024 WCLC｜创新免疫治疗方案：恩沃利单抗联合化疗在II-IIIB期NSCLC中的潜力 2、IF 40.8 | 梁廷波教授团队恩沃利单抗联合仑伐替尼和TACE治疗中晚期肝癌研究结果见刊！ 3、2024 WCLC｜恩维达®治疗鳞状非小细胞肺癌II期临床试验于WCLC大会展示最新临床数据4、2024 ESMO｜恩维达®治疗胆道癌II期临床试验将于ESMO大会展示最新临床数据 5、戴胜教授：新辅助短程放疗序贯恩沃利单抗联合CAPEOX能够给MSS局部晚期直肠癌带来革命性的pCR结果6、2024 ASCO｜恩维达®联合仑伐替尼治疗晚期子宫内膜癌数据以壁报形式首次披露，临床潜力令人期待！7、2024 ASCO｜再创新高！恩沃利单抗9项研究获大会展示8、最新学术进展|恩维达®首次进入胃癌外科领域共识，晚期胆道癌数据将亮相APASL口头报告     关于恩维达®（恩沃利单抗注射液） 恩维达®（恩沃利单抗注射液）由康宁杰瑞自主研发，2016年起与思路迪医药共同开发，2020年3月30日，康宁杰瑞、思路迪医药、先声药业三方达成战略合作，康宁杰瑞作为原研方负责生产和质量，思路迪医药负责肿瘤领域的临床开发，先声药业负责产品在中国大陆的独家商业推广。 基于其独特设计，恩维达®在有效性、安全性、便利性、依从性方面具有优势，患者无需进行静脉滴注，同时有望降低医疗成本。目前在中国、美国和日本针对多个肿瘤适应症同步开展临床试验，多个适应症已进入注册/Ⅲ期临床。恩维达®已被美国FDA授予晚期胆道癌孤儿药资格、软组织肉瘤孤儿药资格。2021年11月，恩维达®正式在中国率先获批上市，适用于不可切除或转移性微卫星高度不稳定(MSI-H)或错配修复基因缺陷型(dMMR)的成人晚期实体瘤患者的治疗，包括既往经过氟尿嘧啶类、奥沙利铂和伊立替康治疗后出现疾病进展的晚期结直肠癌患者以及既往治疗后出现疾病进展且无满意替代治疗方案的其他晚期实体瘤患者。       关于思路迪医药（3D Medicines Inc.） 思路迪医药股份有限公司（1244.HK）是一家进入商业化阶段专注肿瘤慢病化治疗领域的创新药公司，秉承“帮助肿瘤患者活得更久更好”的愿景，研发新一代抗肿瘤药物。公司产品线包括12款具有差异化临床价值或全球领先的创新药，其中8款已进入临床开发或商业化阶段，包括全球首个皮下注射PD-L1单域抗体新药恩维达®已获国家药品监督管理局批准上市销售；依托公司自有mRNA研发平台和肿瘤基因组大数据AI分析平台，研发系列mRNA产品；公司自主研发的多靶点激酶抑制剂3D011也进入了临床开发阶段，临床前品种包括国际领先的CD3xPD-L1双特异性抗体。公司建立了从药物发现、临床前研究、临床开发、申报上市及商业化能力。思路迪医药坚持以患者为中心，开发具有差异化临床价值的创新药。 更多信息请访问： http://www.3d-medicines.com       思路迪医药前瞻性声明 本文所作出的前瞻性陈述仅与本文作出该陈述当日的事件或资料有关。除法律规定外，于作出前瞻性陈述当日之后，无论是否出现新资料、未来事件或其他情况，我们并无责任更新或公开修改任何前瞻性陈述及预料之外的事件。请细阅本文，并理解我们的实际未来业绩或表现可能与预期有重大差异。本文内所有关于或引用的本公司及董事的陈述、观点或意愿乃本文章刊发日期作出，可能因未来发展而出现变动。