Gemcitabine Hydrochloride

自发肿瘤模型区别于诱导模型和移植瘤模型，凭借其独特的生物学特性，成为肿瘤研究中不可替代的工具。其核心优势集中体现在四点： 完整肿瘤微环境（TME）：保留肿瘤与周围基质、免疫细胞的天然相互作用，更贴近临床肿瘤发生发展的真实场景，为肿瘤微环境相关研究（如CAF、TAM调控）提供精准载体。 精准模拟转移与复发：可自然发生肿瘤转移与复发过程，是研究肿瘤侵袭转移机制、评估长期治疗响应的理想模型。 特异性靶基因突变：模型携带明确的原癌基因（KRAS、MYC等）或抑癌基因（p53、APC等）突变，精准匹配人类肿瘤基因特征。 原代细胞可提取：为后续体外机制研究、细胞系构建提供充足的优质样本。 药康生物作为专注于实验动物模型研发与技术服务的国家高新技术企业，长期致力于自发肿瘤模型的系统构建与应用研究。公司已建立覆盖常见肿瘤类型的自发模型资源库，为肿瘤发生机制解析、药物筛选及临床前药效评价提供关键技术支撑。 自发肿瘤模型及应用 胰腺癌 1. B6-KPC小鼠：先构建B6-KP小鼠模型，然后B6-KP和Pdx1-Cre配繁获得B6-KPC，KPC小鼠在10周龄时可发展为胰腺导管癌。 图1. B6-KPC构建策略图 图2. B6-KPC病理检测图 如图2所示，B6-KPC 8-10周龄表现为腺泡-导管化生及胰腺上皮内瘤变( PanIN )，12-16周龄发生浸润性胰腺导管腺癌。 2. mPA-KPC模型：为破解传统KPC模型成瘤慢、监测难的痛点，建立mPA-KPC及其荧光标记细胞系，可实现肿瘤生长动力学精准追溯，为体内药效评估提供可靠工具。 图3. C57BL/6接种PA-KPC细胞系后抗肿瘤药物药效数据 图3结果显示，联合用药方案可实现最高77.74%的肿瘤生长抑制（TGI），助力提升药效验证准确性。 图4. C57BL/6接种mPA-KPC-Luciferase细胞系后药物治疗的肿瘤负荷影像图 图4结果显示，Gemcitabine+anti-CD40 药物联用具有更好的抗肿瘤效果。 乳腺癌 1. FVB-MMTV-PyMT模型：通过MMTV驱动多瘤病毒中间T抗原（PyMT）癌基因在乳腺中高表达，诱发乳腺上皮细胞中PyMT基因的表达失控，进而诱发细胞的恶性增殖，导致乳腺癌发生。 图5. MMTV-PyMT病理检测图 图5A显示，雌鼠6周龄发展为乳腺癌，并出现肺、卵巢及唾液腺转移；图5B显示，雄鼠6周龄部分发展为乳腺癌，并出现唾液腺转移。 2. FVB-MMTV-PyMT应用于药物药效筛选 图6. MMTV-PyMT药效数据（合作验证数据） 第三方合作数据显示，PD-L1抑制剂、CTLA-4抑制剂、小分子酪氨酸激酶抑制剂Lapatinib及小分子酪氨酸激酶抑制剂Palbociclib均展现显著抗肿瘤效果，为药物筛选提供有力支撑。 肠癌 APC-min小鼠：基于APC抑癌基因突变构建，对自发性肠道腺瘤高度易感，可通过高脂饮食调控加速肿瘤发生，清晰模拟结直肠癌发病机制，为肠道肿瘤预防与治疗研究提供优质载体，助力缩短研究周期。 图7. APC-min病理检测图 正常饮食下APC-min 16周龄可见明显腺瘤，高脂饮食下8周龄可见明显腺瘤，如图7所示，APC-min小鼠癌细胞呈菜花样腺管排列，黏膜层及肌层可见大量炎性细胞浸润，结肠中可以发现炎性细胞浸润，肌层纤维组织增生。 图8. APC-min肠道腺瘤情况 如图8所示，正常饮食腺瘤总数0-30不等，高脂饮食的腺瘤总数10-50个。 药康生物自发肿瘤模型资源 除以上常用模型，药康生物同时拥有肝脏、肺部等多类自发肿瘤模型，并不断完善模型矩阵，全方位覆盖更多研究场景。 作者：汪丹丹 审核：Gemma 编辑：Zoe 扫描左侧二维码 有任何技术交流可咨询小吉哟~ 关于药康生物 江苏集萃药康生物科技股份有限公司（科创板代码：688046）是一家专注于实验动物小鼠模型研发、生产及非临床研究服务的国家级高新技术企业，同时是科技部认定的国家遗传工程小鼠资源库共建单位。 依托CRISPR/Cas9、ES打靶等在内的基因编辑技术，公司建立了国际一流的基因修饰动物模型研发平台，拥有近3万种自主知识产权的基因工程小鼠模型品系，其中包括基因敲除/条件性敲除小鼠品系（"斑点鼠计划"）、药靶基因人源化模型、复杂疾病模型、系列免疫缺陷小鼠品系、无菌小鼠品系以及用于抗体药物发现的NeoMab®全人源抗体转基因小鼠，为全球科研机构、CRO公司及医药企业提供全面的模型资源支持。公司提供从基因编辑定制（包括转基因TG、基因敲除KO、基因敲入KI及点突变PM等）、模型繁育到功能药效分析的全流程一站式服务，服务范围涵盖肿瘤、自身免疫性疾病、代谢心血管疾病、神经退行性疾病、感染性疾病及罕见病等重点疾病领域，具体包括靶点验证、药效学评价和非GLP安全性评价等临床前研究。 药康生物致力于成为全球实验动物模型领域的领导者，通过持续深化基因编辑技术的创新应用和资源整合，为生命科学研究和生物医药产业提供高质量的动物模型和技术服务，推动人类健康事业发展。 点赞 收藏 分享

Positive 12-month Phase 2 data for NDV-01 in non-muscle invasive bladder cancer (NMIBC) demonstrated a 95% complete response (CR) rate at any time and a durable 76% CR rate at 12 months, with favorable safety profile Completed an oversubscribed $160 million PIPE financing led by leading healthcare investors in March 2026, strengthens balance sheet to support NDV-01 Phase 3 development On track to initiate Phase 3 RESCUE registrational program in second line (2L) BCG-unresponsive and adjuvant intermediate-risk NMIBC in mid-2026 Cash balance of $93.0 million as of December 31, 2025, plus gross proceeds of $160 million from March 2026 PIPE expected to fund operations through 2029, including completion of the NDV-01 RESCUE program Management to host a conference call and webcast today at 4:30 PM ET CORAL GABLES, Fla., March 19, 2026 (GLOBE NEWSWIRE) -- Relmada Therapeutics, Inc. (Nasdaq: RLMD, “Relmada” or the “Company”), a clinical-stage biotechnology company advancing innovative therapies for oncology and central nervous system disorders, today reported audited financial results for the fourth quarter and full year ended December 31, 2025 and provided a corporate update highlighting significant progress across its pipeline. “This has truly been a transformational year for Relmada, marked by significant progress with our lead program NDV-01,” said Sergio Traversa, Chief Executive Officer of Relmada Therapeutics. “Our recently reported 12-month data for NDV-01 demonstrated durable complete responses with a favorable safety profile, reinforcing the program’s potential to become a best-in-class therapy for patients with non-muscle invasive bladder cancer. With a successful $160 million PIPE financing and regulatory alignment with the FDA on two registrational pathways, we believe that we are well positioned to advance NDV-01 into the Phase 3 RESCUE program in mid-2026. Our team is now focused on executing this plan and initiating the RESCUE registrational program as we work to bring NDV-01 to patients as efficiently as possible.” “NDV-01’s compelling efficacy, durability, and favorable safety profile, combined with operational ease-of-use are the cornerstone of its differentiated product pro best-in-class potential,” said Raj S. Pruthi, MD, Chief Medical Officer-Oncology of Relmada Therapeutics . “We continue to be encouraged by the high response rates and durable clinical benefit observed through 12 months, including in the BCG-unresponsive population, alongside a favorable safety pro no ≥ Grade 3 treatment-related adverse events and no treatment-related discontinuations. Our clinical program builds on the urologic oncology community’s comfort with conventional Gem/Doce’s efficacy and safety pro a sustained release product that could provide physicians and patients with a streamlined, less than 5-minute in-office procedure. These results reinforce our confidence as we advance NDV-01 into the Phase 3 RESCUE registrational program in mid-2026.” Highlights of the 12-month follow-up data from the ongoing Phase 2 study of NDV-01: In the 12-month follow-up of the Phase 2a study (March 9, 2026 Company press release) treatment with NDV-01 produced: Durable 76% complete response (CR) rate at 12 months with 95% CR rate at any time in high-risk NMIBC BCG-unresponsive patients achieved an 80% CR rate at 12 months and 94% CR rate at any time No patient had progression to muscle-invasive disease, and no patient underwent a radical cystectomy Favorable overall tolerability – no ≥ Grade 3 treatment-related adverse events and no treatment-related discontinuations or dose interruptions. Phase 3 RESCUE Registrational Pathways: As previously disclosed in the Company’s January 12, 2026 regulatory update, Relmada has received written feedback from the U.S. Food and Drug Administration (FDA) confirming alignment on two registrational development pathways for NDV-01, including study design, patient populations and primary endpoints. Registrational Pathway 1 – An open label randomized controlled trial in intermediate-risk NMIBC of adjuvant therapy following TURBT (NDV-01 vs. observation). There are no approved treatments for adjuvant intermediate risk NMIBC, which we estimate affect ~75,000 patients/year in the U.S. The primary endpoint of the study is disease free survival (DFS). Registration Pathway 2 – A single-arm trial in second line (2L) BCG-unresponsive NMIBC with carcinoma in situ (CIS) patients who are currently refractory to approved or developmental therapies. Patients with BCG-unresponsive NMIBC with CIS who fail first line (1L) therapies, which we estimate to affect ~5,000 patients/year in the U.S., have few, if any, effective treatment alternatives to radical cystectomy. The primary endpoint of the study is complete response (CR) rate at any time. Expected Upcoming Relmada Milestones: NDV-01 United States IND clearance – Mid-2026 NDV-01 Phase 3 RESCUE Program initiation – Mid-2026 Sepranolone Phase 2 initiation in Prader-Willi syndrome – Mid-2026 Initial 3-month NDV-01 data from Phase 3 2L BCG-unresponsive study expected by YE 2026 Financial Results Fourth Quarter 2025 Financial Results Research and development expense for the three months ended December 31, 2025, totaled $8.1 million, compared to $11.0 million for the three months ended December 31, 2024, a decrease of $2.9 million. The decrease was primarily driven by a decrease in study costs associated with the completion of two Phase 3 trials for REL-1017, partially offset by increased costs related to the start-up the Phase 3 NDV-01 trials and Phase 2b sepranolone study and additional R&D personnel. General and administrative expense for the three months ended December 31, 2025, totaled $12.3 million compared to $8.1 million for the three months ended December 31, 2024, an increase of approximately $4.2 million. The increase was primarily driven by an increase in compensation costs partially offset by a decrease in stock based compensation costs. Net cash used in operating activities for the three months ended December 31, 2025, totaled $14.6 million compared to $8.8 million for the three months ended December 31, 2024. The net loss for the three months ended December 31, 2025, was $19.9 million, or $0.27 per basic and diluted share, compared with a net loss of $18.6 million, or $0.62 per basic and diluted share, for the three months ended December 31, 2024. Twelve Month Ended December 31, 2025 Financial Results Research and development (R&D) expense for the 12 months ended December 31, 2025, totaled $26.9 million, compared to $46.2 million for the 12 months ended December 31, 2024, a decrease of $19.3 million. The decrease was primarily driven by a decrease in study costs associated with completion and conclusion of two Phase 3 trials for REL-1017, partially offset by increased costs related to the acquisition of NDV-01 and sepranolone, as well as the start-up of the Phase 3 NDV-01 trials and Phase 2b sepranolone study. General and administrative (G&A) expense for the 12 months ended December 31, 2025, totaled $32.2 million compared to $37.7 million for the 12 months ended December 31, 2024, a decrease of approximately $5.5 million. The decrease was primarily driven by a decrease in stock-based compensation expense and lower professional fees, partially offset by an increase in personnel-related costs. Net cash used in operating activities for the 12 months ended December 31, 2025, totaled $45.8 million compared to $51.8 million for the 12 months ended December 31, 2024. The net loss for the 12 months ended December 31, 2025, was $57.4 million, or $1.45 per basic and diluted share, compared with a net loss of $80.0 million, or $2.65 per basic and diluted share, for the 12 months ended December 31, 2024. The Company’s cash balance of $93.0 million in cash, cash equivalents, and short-term investments, includes net proceeds of approximately $94 million from an underwritten stock offering announced November 5, 2025. This compares to cash, cash equivalents, and short-term investments of approximately $44.9 million at December 31, 2024. On March 9, 2026, the Company announced a private financing with gross proceeds of $160 million. This financing, along with the cash, cash equivalents, and short-term investments as of December 31, 2025, is expected to provide sufficient resources to fund Company operations through 2029, including completion of the Phase 3 NDV-01 RESCUE program. The Company had 104,890,223 shares outstanding, as of March 16, 2026 Conference Call and Webcast Information: Relmada will host a conference call and webcast today at 4:30 PM ET to discuss recent business progress and financial results. Conference Call and Webcast Information: Date: Thursday, March 19, 2026 at 4:30 PM ET Participant Dial-in (US): 1-877-407-0792 Participant Dial-in (International): 1-201-689-8263 Webcast Access: Click Here A replay of the webcast will be available in the Investors section of the Relmada website at . About NDV-01 NDV-01 is a sustained-release, intravesical formulation of gemcitabine and docetaxel (Gem/Doce), in development for the treatment of non-muscle invasive bladder cancer. It is designed to enable Gem/Doce bladder retention and gradual drug release over 10 days. The formulation creates a soft matrix that enhances local exposure while minimizing systemic toxicity. The NDV-01 formulation is ready to use, convenient to administer in-office in less than 5 minutes and does not require anesthesia or specialized equipment. It is protected by patents through 2038. About the Phase 2 Study The Phase 2 study (NCT06663137) is an open-label, single-arm, single-center study evaluating the safety and efficacy of NDV-01 in patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC). Patients are treated with NDV-01 in a biweekly induction phase, followed by monthly maintenance for up to one year, with regular assessments via cystoscopy, cytology, and biopsy, as indicated. The primary efficacy endpoints are safety and complete response rate (CRR) at 12 months, and secondary efficacy endpoints are duration of response (DOR) and event free survival (EFS). About NMIBC NMIBC represents 75-80% of all bladder cancer cases and is associated with high recurrence (50 – 80% over 5 years). With over 744,000 prevalent cases in the U.S. and limited treatment options, the market opportunity is significant. High-grade BCG-unresponsive disease represents one of the most difficult-to-treat NMIBC subtypes, with limited bladder-sparing options. Intermediate-risk NMIBC in the adjuvant setting has no currently approved therapies. NDV-01 has the potential to serve as a frontline or salvage therapy and could be applicable across multiple NMIBC subtypes. About Sepranolone and GABA Modulation Sepranolone, a synthetic isoallopregnanolone, selectively modulates GABA A receptors by antagonizing allopregnanolone (ALLO), without disrupting GABA signaling. It targets disorders linked to excess GABAergic activity such as Prader-Willi syndrome, Tourette syndrome, and Obsessive-Compulsive Disorder (OCD). More than 335 patients have been treated with sepranolone in clinical trials to date, with an excellent safety profile. About Prader-Willi Syndrome (PWS) PWS is a rare genetic disorder caused by chromosomal deletions on chromosome 15, leading to neurodevelopmental and behavioral complications. Global prevalence is estimated to be 350,000-400,000 patients. Current treatments address symptoms but do not modify the underlying neurobehavioral pathology. About Relmada Therapeutics, Inc. Relmada Therapeutics is a clinical-stage biotechnology company focused on developing transformative therapies for oncology and central nervous system conditions. Its lead candidates, NDV-01 and sepranolone, are advancing through mid-stage clinical development with the potential to address significant unmet needs. For more information, visit Forward-Looking Statements: The Private Securities Litigation Reform Act of 1995 provides a safe harbor for forward-looking statements made by us or on our behalf. This press release contains statements which constitute “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Any statement that is not historical in nature is a forward-looking statement and may be identified by the use of words and phrases such as “if”, “may”, “expects”, “anticipates”, “believes”, “will”, “will likely result”, “will continue”, “plans to”, “potential”, “promising”, and similar expressions. These statements are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including potential for Relmada’s product candidates to progress, including the potential for Phase 2 NDV-01 data to continue to deliver positive results supporting further development, potential for clinical trials to deliver statistically and/or clinically significant evidence of efficacy and/or safety, failure of interim or top-line results to accurately reflect the complete results of the trial, failure of planned or ongoing preclinical and clinical studies to demonstrate expected results, potential failure to continue to secure FDA agreement on the regulatory path for NDV-01 and/or sepranolone, or that future NDV-01 and/or sepranolone clinical results will be acceptable to the FDA, failure to secure adequate NDV-01 and/or sepranolone drug supply, the Company’s cash runway and sufficiency of the Company’s cash resources and uncertainties inherent in estimating the Company’s cash runway, future expenses and other financial results, including its ability to fund future operations, including clinical trials, and the other risk factors described under the heading “Risk Factors” set forth in the Company’s reports filed with the SEC from time to time. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Relmada undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Readers are cautioned that it is not possible to predict or identify all the risks, uncertainties and other factors that may affect future results and that the risks described herein are not a complete list. Investor Contact: Brian Ritchie LifeSci Advisors britchie@lifesciadvisors.com Media Inquiries: Corporate Communications media@relmada.com Relmada Therapeutics, Inc. Condensed Consolidated Balance Sheets (Audited) As of As of December 31, December 31, 2025 2024 Assets Current assets: Cash and cash equivalents $ 3,496,540 $ 3,857,026 Short-term investments 89,509,710 41,052,356 Prepaid expenses 977,721 886,461 Total current assets 93,983,971 45,795,843 Other assets 19,500 21,975 Total assets $ 94,003,471 $ 45,817,818 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 1,568,944 $ 4,130,563 Accrued expenses 4,861,583 6,160,827 Total current liabilities 6,430,527 10,291,390 Stock appreciation rights 1,060,931 4,467 Total liabilities 7,491,458 10,295,857 Commitments and Contingencies (Note 10) Stockholders’ Equity: Preferred stock, $0.001 par value, 200,000,000 shares authorized, none issued and outstanding - - Class A convertible preferred stock, $0.001 par value, 3,500,000 shares authorized, none issued and outstanding - - Common stock, $0.001 par value, 150,000,000 shares authorized, 73,333,622 and 30,174,202 shares issued and outstanding, respectively 73,333 30,174 Additional paid-in capital 784,705,878 676,373,822 Accumulated deficit (698,267,198 ) (640,882,035 ) Total stockholders’ equity 86,512,013 35,521,961 Total liabilities and stockholders’ equity $ 94,003,471 $ 45,817,818 Relmada Therapeutics, Inc. Condensed Consolidated Statements of Operations (Audited) 2025 2024 Operating expenses: Research and development $ 26,879,146 $ 46,175,512 General and administrative 32,221,054 37,715,524 Total operating expenses 59,100,200 83,891,036 Loss from operations (59,100,200 ) (83,891,036 ) Other income (expenses): Interest/investment income, net 1,395,989 3,530,021 Realized (loss) gain on short-term investments (79,207 ) 374,926 Unrealized gain on short-term investments 398,255 6,735 Total other income (expenses), net 1,715,037 3,911,682 Net loss $ (57,385,163 ) $ (79,979,354 ) Net loss per common share – basic and diluted $ (1.45 ) $ (2.65 ) Weighted average number of common shares outstanding – basic and diluted 39,479,694 30,163,751 Relmada Therapeutics, Inc. Condensed Consolidated Statements of Stockholders’ Equity (Audited) Common Stock Additional Paid-in Accumulated Balance – December 31, 2023 30,099,203 $ 30,099 $ 646,229,824 $ (560,902,681 ) $ 85,357,242 Stock-based compensation expense - - 30,184,414 - 30,184,414 Net proceeds from cash exercise option 74,999 75 246,672 - 246,747 ATM fees - - (287,088 ) - (287,088 ) Net loss - - - (79,979,354 ) (79,979,354 ) Balance – December 31, 2024 30,174,202 30,174 676,373,822 (640,882,035 ) 35,521,961 Stock-based compensation expense - - 13,905,181 - 13,905,181 Issuance of restricted common stock 3,017,420 3,017 902,209 - 905,226 Net proceeds from cash exercise options 40,142,000 40,142 93,597,687 - 93,637,829 ATM fees - - (73,021 ) - (73,021 ) Net loss - - - (57,385,163 ) (57,385,163 ) Balance – December 31, 2025 73,333,622 $ 73,333 $ 784,705,878 $ (698,267,198 ) $ 86,512,013 Relmada Therapeutics, Inc. Condensed Consolidated Statements of Cash Flows (Audited) 2025 2024 Cash flows from operating activities Net loss $ (57,385,163 ) $ (79,979,354 ) Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 13,905,181 30,184,414 Stock appreciation rights compensation 1,056,464 4,467 Issuance of restricted common stock 905,226 - Realized (gain) loss on short-term investments 79,207 (374,926 ) Unrealized gain on short-term investments (398,255 ) (6,735 ) Change in operating assets and liabilities: Prepaid expenses and other assets (88,785 ) 319,746 Accounts payable (2,561,619 ) 624,554 Accrued expenses (1,299,244 ) (2,527,964 ) Net cash used in operating activities (45,786,988 ) (51,755,798 ) Cash flows from investing activities Purchase of short-term investments (83,828,576 ) (12,079,628 ) Sale of short-term investments 35,690,270 63,641,225 Net cash (used in)/provided by investing activities (48,138,306 ) 51,561,597 Cash flows from financing activities Proceeds from issuance of common stock, net 93,637,829 - Payment of ATM fees (73,021 ) (287,088 ) Proceeds from options exercised for common stock - 246,747 Net cash provided by/(used in) financing activities 93,564,808 (40,341 ) Net decrease in cash and cash equivalents (360,486 ) (234,542 ) Cash and cash equivalents at beginning of the year 3,857,026 4,091,568 Cash and cash equivalents at end of the year $ 3,496,540 $ 3,857,026