Picibanil

TARA-002 demonstrates 72% six-month landmark complete response rate and 70% complete response rate at any time across BCG exposures 100% six-month landmark complete response rate and 80% complete response rate at any time observed in BCG-Unresponsive patients 64% six-month landmark complete response rate and 67% complete response rate at any time observed in BCG-Naïve patients 80% reinduction salvage rate and compelling durability observed with 100% of patients maintaining a complete response from three months to six months across BCG exposures Favorable safety and tolerability profile with no Grade 2 or greater treatment-related adverse events Company to host conference call and webcast today at 8:30 a.m. ET Dec. 05, 2024 -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced results from its ongoing Phase 2 open-label ADVANCED-2 trial. The trial is assessing intravesical TARA-002, the Company’s investigational cell-based therapy, in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive or BCG-Naïve. The complete response (CR) rate across BCG exposures was 72% (13/18) at six months and 70% (14/20) at any time with 100% (9/9) of patients maintaining a CR from three months to six months. In addition, two of three patients maintained a CR at nine months. These results will be featured today during a poster session at the 25th Annual Meeting of the Society of Urologic Oncology (SUO) in Dallas, Texas. The dataset includes 20 patients who were evaluable at three months, 18 patients who were evaluable at six months and three patients who were evaluable at nine months with a data cutoff of November 19, 2024. In the pivotal cohort of the ADVANCED-2 trial in BCG-Unresponsive patients, the CR rate was 100% (4/4) at six-months and 80% (4/5) at any time. In the proof-of-concept cohort of BCG-Naïve patients, the CR rate was 64% (9/14) at six months and 67% (10/15) at any time. TARA-002 demonstrated a favorable safety and tolerability profile with no Grade 2 or greater treatment-related adverse events (TRAEs), and no patients discontinued due to adverse events. “These impressive TARA-002 results demonstrate meaningful activity in a difficult to treat patient population,” said Brian Mazzarella, MD, Vice President of Research for Urology America, and ADVANCED-2 study investigator. “The activity of TARA-002 across BCG exposures, coupled with its ease of use and low procedural burden for physicians, make it an exciting potential treatment option for NMIBC patients.” “We are thrilled with these positive six-month data, which reinforce TARA-002’s potential in NMIBC, while offering a compelling product profile for physicians and patients,” said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. “We believe these encouraging data together with our international site expansion will accelerate patient enrollment, and we look forward to reporting initial data from 12-month evaluable patients in mid-2025.” The majority of adverse events were Grade 1 and transient with no Grade 2 or greater TRAEs as assessed by study investigators. No patients discontinued treatment due to adverse events. The most common adverse events were in line with typical responses to bacterial immunopotentiation, such as flu-like symptoms. The most common urinary symptoms reflect urinary tract instrumentation effects, such as bladder spasm, burning sensation, and urinary tract infection. Most bladder irritations resolved shortly after administration or within a few hours to a few days. The Phase 2 open-label ADVANCED-2 trial is assessing intravesical TARA-002 in NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive (n≈100) and BCG-Naïve (n=27). The BCG-Unresponsive cohort has been designed to be registrational in alignment with the FDA’s 2024 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment Draft Guidance for Industry. TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil® in Japan and approved in Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432. When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-1b, IL-6, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and natural killer cells. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response. Bladder cancer is the sixth most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle. Protara is a clinical-stage biotechnology company committed to advancing transformative therapies for people with cancer and rare diseases. Protara’s portfolio includes its lead candidate, TARA-002, an investigational cell-based therapy in development for the treatment of non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs). The Company is evaluating TARA-002 in an ongoing Phase 2 trial in NMIBC patients with carcinoma in situ (CIS) who are unresponsive or naïve to treatment with Bacillus Calmette-Guérin (BCG), as well as a Phase 2 trial in pediatric patients with LMs. Additionally, Protara is developing IV Choline Chloride, an investigational phospholipid substrate replacement for patients on parenteral nutrition who are otherwise unable to meet their choline needs via oral or enteral routes. For more information, visit www.protaratx.com. The content above comes from the network. if any infringement, please contact us to modify.

▎药明康德内容团队编辑 Protara Therapeutics公司日前公布了正在进行中的开放标签2期临床试验ADVANCED-2的最新结果。该试验评估了其在研细胞疗法TARA-002对携带高风险原位癌的非肌层浸润性膀胱癌（NMIBC）患者的疗效，包括对卡介苗（BCG）无应答或为BCG初治患者。 主要研究结果显示： 在所有患者中，接受治疗后6个月时的完全缓解（CR）率为72%（13/18），任意时间点的CR率为70%（14/20）。 在接受治疗后3个月时获得完全缓解的9名患者中，所有患者在6个月时均维持完全缓解。 在3位随访时间达到9个月的可评估患者中，有2位在9个月时仍保持完全缓解。 值得一提的是，在对BCG无应答的患者队列中，接受治疗6个月时的CR率为100%（4/4），任意时间点的CR率为80%（4/5）。 ▲TARA-002的2期临床试验疗效结果（图片来源：Protara Therapeutics公司官网） TARA-002展现出良好的安全性和耐受性，没有观察到2级或更高的治疗相关不良事件（TRAEs）。大多数不良事件为1级，且为短暂性，没有患者因不良事件而停止治疗。最常见的不良事件包括与细菌免疫增强反应相关的流感样症状，以及尿路操作引起的膀胱痉挛、灼热感和尿路感染等尿路症状，且大多在给药后数小时至几天内缓解。 TARA-002是一款在研细胞疗法，基于一种失活的化脓性链球菌（Streptococcus pyogenes）菌株。该菌株与已在日本获批上市的Picibanil源于同一主细胞库。Picibanil已经在日本获批用于治疗某些癌症和淋巴管瘤。TARA-002给药后，预计会激活囊肿或肿瘤内的先天性和适应性免疫细胞，产生促炎性反应，释放多种细胞因子（如TNF-α、IFN-γ、IL-1b、IL-6、IL-12、GM-CSF）。此外，TARA-002可直接杀死肿瘤细胞，并通过诱导免疫原性细胞死亡（ICD）触发宿主免疫反应，从而进一步增强抗肿瘤免疫反应。 图片来源：123RF 膀胱癌是常见癌症之一，其中约80%为非肌层浸润性膀胱癌。仅在美国，每年约有六万五千例NMIBC新确诊病例，NMIBC是指局限于膀胱内壁表层组织、未扩散至膀胱肌肉的癌症类型。BCG是治疗这些患者的标准疗法。近年来，多家公司在开发BCG之外的NMIBC疗法方面获得显著进展。今年4月，美国FDA批准ImmunityBio旗下Altor BioScience所开发的白细胞介素-15（IL-15）超级激动剂Anktiva（nogapendekin alfa inbakicept）与BCG联合使用，用于治疗对BCG无应答且伴有原位癌（CIS）的NMIBC成年患者。在2/3期临床试验中，患者达到62%的CR率。 此外，CG Oncology公司的在研溶瘤病毒疗法cretostimogene，在治疗对卡介苗无应答的高风险NMIBC患者的3期临床试验中获得积极结果。74.5%（82/110）的患者达到完全缓解。而且，中位缓解持续时间超过27个月。这款疗法已经被美国FDA授予突破性疗法认定和快速通道资格。 enGene公司的主打非病毒基因疗法detalimogene voraplasmid（也称为detalimogene）在高风险、对BCG无应答、伴有原位癌的NMIBC患者中进行的LEGEND关键性试验中也获得积极结果。日前发布的数据显示，高达71%的患者达成完全缓解。 强生公司的在研膀胱内靶向释放疗法TAR-210在治疗携带特定FGFR基因变异的NMIBC患者的1期临床试验中也获得积极结果。在C3队列中，完全缓解率达到90%。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Protara Announces Positive Results from the Ongoing Phase 2 ADVANCED-2 Trial of TARA-002 in Patients with NMIBC. Retrieved December 5, 2024, from https://www.globenewswire.com/news-release/2024/12/05/2992222/0/en/Protara-Announces-Positive-Results-from-the-Ongoing-Phase-2-ADVANCED-2-Trial-of-TARA-002-in-Patients-with-NMIBC.html [2] ADVANCED-2 TRIAL INTERIM RESULTS. Retrieved December 5, 2024, from https://ir.protaratx.com/static-files/e1220a6b-ce19-4fce-9b14-27407f102068 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新