DD-01

罗氏推进潜在“first-in-class”帕金森疗法进入3期试验罗氏（Roche）宣布，将推进其在研潜在“first-in-class”单克隆抗体prasinezumab的3期临床开发，用于早期帕金森病的治疗。该决定基于2b期PADOVA研究及其开放标签扩展（OLE）研究，以及早期PASADENA研究的持续随访数据。Prasinezumab旨在靶向结合聚集的α-突触核蛋白，从而减少神经毒性，减缓其在脑内的积聚及细胞间传播，有望延缓疾病进展。在PADOVA研究中，586名处于早期阶段的帕金森病患者在稳定的对症治疗基础上接受prasinezumab治疗至少18个月。尽管主要终点“确诊运动功能恶化的时间”未达到统计学显著性（HR=0.84，p=0.0657），但数据显示其可能带来临床获益，尤其是在接受左旋多巴治疗的75%受试者中观察到更显著疗效（HR=0.79，p=0.0431）。多项次要及探索性终点也呈现出一致的积极趋势。Prasinezumab在安全性方面耐受性良好，未发现新的安全信号，目前已有逾900名患者接受治疗，其中超750人持续参与OLE研究，超过500人治疗时间已达1.5至5年。超80%肿瘤患者达完全缓解！潜在“first-in-class”单抗积极数据公布Incyte近日公布其创新疗法INCA033989的首个临床研究数据，该药物为一款潜在“first-in-class”、突变型钙网蛋白（mutCALR）靶向单克隆抗体，用于治疗携带此突变的骨髓增殖性肿瘤（MPN）患者。数据显示，在接受INCA033989治疗的高危原发性血小板增多症（ET）的患者中，各剂量组均实现了快速且持久的血小板计数正常化，高剂量组（>400 mg）患者应答更为显著。其中，86%的患者达到完全或部分血液学缓解，82%达完全缓解；89%（34/38）的可评估患者mutCALR等位基因频率（VAF）降低，且21%（8/38）患者在仅接受3个治疗周期后即实现超过50%的VAF下降。单细胞DNA测序探索性研究进一步显示，INCA033989能够选择性靶向并减少携带mutCALR的造血干祖细胞（CD34阳性）及髓红系细胞，同时促进正常（野生型CALR）细胞的恢复，支持健康造血功能的重建。骨髓活检结果亦验证了这一机制，mutCALR阳性巨核细胞减少、阴性巨核细胞增加。安全性方面，INCA033989在24至2500 mg的全部剂量范围内耐受性良好，无剂量限制性毒性（DLT），仅1例患者因治疗伴发不良事件（TEAEs）停药，另有1例发生剂量调整。最常见的TEAEs为疲劳（26.5%）和上呼吸道感染（20.4%），均为1-2级。超75%患者肝脂肪下降！MASH疗法最新结果公布D&D Pharmatech今日公布其在研药物DD01的积极临床进展。该公司正在开展一项为期48周的2期临床试验DD01-DN-02，旨在评估DD01在超重/肥胖的代谢功能障碍相关脂肪性肝炎（MASH）患者中的疗效与安全性。试验采用每周一次给药方案，以20 mg为起始剂量持续两周，随后进入40 mg维持剂量阶段。在第12周的预计疗效与安全性评估中，研究达成主要终点，DD01显示良好耐受性，并显著降低肝脂含量：75.8%的受试者肝脂下降≥30%，72.7%下降≥50%，57.6%下降≥70%（均p<0.0001）；平均肝脂含量下降62.3%，而安慰剂组仅为8.3%。此外，48.5%的DD01组患者实现肝脂含量正常化（经磁共振成像-质子密度脂肪分数[MRI-PDFF]测定≤5%），而安慰剂组无患者实现此标准。除肝脂下降外，DD01还在多个无创MASH进展指标上展现出积极疗效，包括肝脏硬度（MRE）等评分的显著改善。DD01是一款每周一次给药的GLP-1/胰高血糖素受体双重激动剂，在2型糖尿病与MASLD患者中半衰期约为7-8天。根据该疗法1期结果显示能快速改善肝脂沉积、糖耐量及体重，FDA授予其治疗MASH的快速通道资格。此次2期结果进一步验证了其药理作用的一致性与临床潜力。▲DD01药物试验结果摘要（图片来源：参考资料[3]）参考资料：[1] Roche to advance prasinezumab into Phase III development for early-stage Parkinson's disease. Retrieved June 16, 2025 from https://www.roche.com/media/releases/med-cor-2025-06-16[2] Positive Late-Breaking Data for Incyte’s First-in-Class mutCALR-targeted therapy INCA033989 in Essential Thrombocythemia Presented at EHA2025. Retrieved June 16, 2025 from https://investor.incyte.com/news-releases/news-release-details/positive-late-breaking-data-incytes-first-class-mutcalr-targeted[3] D&D Pharmatech Announces Positive Phase 2 Results for DD01 in MASH with Robust Reductions in Liver Fat Accompanied by Improvements in Liver and Metabolic Health. Retrieved June 16, 2025 from https://www.businesswire.com/news/home/20250616477730/en/DD-Pharmatech-Announces-Positive-Phase-2-Results-for-DD01-in-MASH-with-Robust-Reductions-in-Liver-Fat-Accompanied-by-Improvements-in-Liver-and-Metabolic-Health免责声明：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：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

GYEONGGI-DO, South Korea & GAITHERSBURG, MD, USA I June 16, 2025 I D&D Pharmatech, Inc. (D&D) (KOSDAQ: 347850), a clinical-stage biotechnology company developing breakthrough treatments for liver and metabolic diseases, today announced positive results from DD01-DN-02 study, an ongoing 48-week Phase 2 trial designed to evaluate the efficacy and safety of DD01 (a once-weekly dual GLP1/glucagon receptor agonist) in 67 overweight/obese subjects with MASH. DD01 treatment was initiated with two weeks of dosing at 20 mg, followed by the 40mg once-weekly maintenance dose. Results of a planned 12-week assessment of safety and efficacy revealed DD01 was well tolerated, and the study’s primary endpoint was met. Following a 1:1 randomization of 40mg DD01 and placebo, 75.8% of subjects treated with DD01 achieved at least a 30% reduction in liver fat, 72.7% of subjects achieved greater than 50% reduction in liver fat, and 57.6% of subjects achieved greater than 70% liver fat reduction (in each case, with p < 0.0001). DD01 achieved a mean reduction of liver fat content of 62.3% vs 8.3% for placebo at 12 weeks of treatment, and 48.5% of DD01 subjects achieved normalization of liver fat fraction (defined as liver fat fraction of 5% or less by MRI-PDFF). No placebo subject achieved normalization. Treatment related reductions in Non-invasive markers of MASH progression were used to evaluate subjects at baseline and after 12 weeks of treatment. DD01 treatment was associated with statistically significant improvements in liver stiffness (MRE), pro-C3 levels, and ELF score. Additional Endpoints Twelve-week weight loss data were encouraging. While placebo-treated subjects had no significant weight loss, 42.4% of DD01-treated subjects achieving a greater than 5% reduction in weight. Also encouraging were the results of HbA1c testing. While the study population was not selected to be diabetic, following 12 weeks of DD01 treatment, HbA1c reduction was statistically significant compared to placebo. Safety Results DD01 was well tolerated. Gastrointestinal (GI) side effects were most common, generally mild to moderate, but transient and manageable. To date, only 3 subjects have discontinued treatment due to GI-related adverse events. Implications Seulki Lee, Ph.D., President and Chief Executive Officer of D&D Pharmatech , stated,“We have remarkably positive results for DD01 after only 12 weeks of treatment in MASH. The magnitude of improvements is equivalent to what has been achieved only after longer-term treatment with FGF and GLP-1 based drugs already validated with histology data in MASH.” “Considering the combination of liver and metabolic benefits and the favorable tolerability profile, DD01 has the potential to provide patients and physicians with a MASH treatment that is easy to manage, encourages weight loss and is diabetes friendly.” Mazen Noureddin, MD, MHSc, Professor of Medicine at Houston Methodist Hospital; Co-Chairman of the Board, Summit & Pinnacle Clinical Research; Director, Houston Research Institutes , commented,“The degree of liver fat reduction with DD01 is striking, with nearly three-quarters of patients achieving at least a 30% reduction and almost half reaching normalization within just 12 weeks. The observed improvement in liver stiffness by MRE, though early, adds further support to the biological activity of this dual GLP-1/glucagon approach, which is designed to act directly on the liver.” “These consistent MRI-PDFF results provide strong confidence that DD01 has the potential to meet both key regulatory endpoints – MASH resolution and fibrosis improvement – as the program advances. Coupled with favorable metabolic effects and a very low treatment discontinuation rate, DD01 is emerging as a well-differentiated and promising therapy, both within its class and compared to other potent agents in development.” Additional data will be presented at upcoming medical meetings. About DD01 DD01 is a once-weekly dual GLP1/glucagon receptor agonist with a half-life of 7-8 days in obese/overweight patients with T2D and MASLD. Following a Phase 1 study that showed DD01 rapidly reduced liver steatosis, improved glucose tolerance, and encouraged weight loss in obese subjects with MASLD and type 2 diabetes, FDA granted DD01 Fast Track Designation for the treatment of MASH. Current Phase 2 results confirm and extend these findings revealing additional benefits in patients with MASH. The effect of DD01 is consistent with its dual-agonist pharmacology. Clinical results show the effects of DD01 are remarkably rapid. DD01 achieves robust results rapidly and with tolerability comparable to other validated MASH treatments. The GLP1:glucagon potency ratio for DD01 is 11:1. GLP-1R potency is likely an important driver in glucose management for diabetic patients and in weight loss. Importantly, with this ratio, DD01 is clearly also a potent glucagon receptor agonist. Substantial liver fat reduction was observed after only 4 weeks in obese subjects with MASLD (Phase 1). Liver fat reduction by DD01 is clearly not secondary to weight loss at these early timepoints, differentiating it mechanistically from the pure incretin approach. In terms of the balance between efficacy and tolerability, the pharmacokinetics of DD01 are also unique. Good tolerability at clinically active doses is likely aided by very slow absorption (tmax = 6 days) and a long half-life (7-8 days), features which make the onset and rise in DD01 exposure gradual. Peaks associated with poor tolerability and troughs associated with diminished efficacy are avoided. As a result, the need for a lengthy titration period is eliminated and therapeutic levels are reached rapidly. A key differentiator for DD01 is the balanced constellation of clinical benefits afforded by a unique pharmacologic and pharmacodynamic signature. Current data suggest DD01 has the necessary attributes to offer patients and physicians a treatment that is easy to use, supports both liver and metabolic health. About the DD01-DN-02 Trial With the support of staff at Summit Clinical Research, the study investigators, and the study participants, the DD01-DN-02 study is fully enrolled and currently ongoing at 12 centers in the U.S. Baseline characteristics were well balanced between both treatment groups with nearly identical mean liver fat fractions (overall mean of 20.7%) and similar body weight (overall mean 99.4 kg) at baseline. Treatment is ongoing and the study includes non-invasive and histologic assessments of MASH resolution and change in fibrosis at 48 weeks. More information about the study is available at www.clinicaltrials.gov under the identifier NCT06410924. About D&D Pharmatech D&D Pharmatech is a clinical-stage biopharmaceutical company focused on developing revolutionary medicines for patients with a number of metabolic, fibrotic, and neurodegenerative diseases. DD01 and TLY012 are in development for fibrotic liver disease (MASH and cirrhosis). TLY012 has completed IND-enabling studies and has been shown to slow and even reverse established fibrosis in models of liver cirrhosis, chronic pancreatitis, and systemic scleroderma. Two products are in development for neurodegenerative diseases. NLY02 is a small molecule BBB penetrating kinase inhibitor targeting glial activation. It is a potent inhibitor of neurodegeneration. NLY01 is also a potent inhibitor of glial activation. It acts through the incretin pathway to reduce neuronal loss and slow functional decline in models of Parkinson’s, Alzheimer’s, and multiple sclerosis. In a recently completed Phase 2 study conducted in >250 Parkinson’s patients, 36-week of treatment with NLY01 resulted in a significant reduction in motor function decline (UPDRS III) in ~1/3 of trial subjects. NLY01 appeared to slow the progressive decline in motor function in newly diagnosed patients who were young (<60) and treatment naïve. D&D Pharmatech’s ORALINK technology allows efficient oral uptake of therapeutic peptides. In partnership with Metsera, the company is developing orally active incretin-based peptide drugs for obesity. SOURCE: D&D Pharmatech