Medicenna Presents Updated Results of Single Agent MDNA11 Anti-tumor Activity From Dose Escalation and Ongoing Dose Expansion of the Phase 1/2 ABILITY-1 Study at the 2024 Annual Meeting of the American Association for Cancer Research (AACR)
Medicenna Presents Updated Results of Single Agent MDNA11 Anti-tumor Activity From Dose Escalation and Ongoing Dose Expansion of the Phase 1/2 ABILITY-1 Study at the 2024 Annual Meeting of the American Association for Cancer Research (AACR)
100% reduction of target lesions in one melanoma and one pancreatic cancer patient observed among 4 Partial Responses (PR) to date which include 2 of 4 evaluable dose expansion patients and 2 of 2 MSI-H patients
迄今为止，在4种局部反应（PR）中观察到一例黑色素瘤和一名胰腺癌患者的目标病变减少了100％，其中包括4名可评估剂量扩展患者中的2名和2名MSI-H患者中的2例
Durable stable disease (SD) in 3 melanoma patients for 6 to 18 months with concomitant tumor shrinkage
3 名黑色素瘤患者持续6至18个月的持久稳定疾病（SD），伴随肿瘤萎缩
With response rate and clinical benefit rate increasing to 29% and 50% (4 PR, 3 SD), respectively, MDNA11 continues to demonstrate compelling single-agent activity in the ABILITY-1 study amongst high-dose phase-2 eligible patients (N=14) who have failed checkpoint inhibitor therapies
随着缓解率和临床获益率分别提高到 29% 和 50%（4 PR，3 SD），MDNA11 在 ABILITY-1 研究中继续在检查点抑制剂疗法失败的高剂量 2 期合格患者（N=14）中表现出令人信服的单药活性
MDNA11 is generally well tolerated with no dose-limiting toxicities or vascular leak syndrome reported in any of the dose escalation cohorts
MDNA11 的耐受性通常良好，在任何剂量递增队列中均未报告剂量限制毒性或血管泄漏综合征
Medicenna believes that these data reaffirm the differentiated and promising therapeutic activity, safety, PD and PK profile of MDNA11 in patients with advanced solid tumors who have failed multiple prior lines of therapies
Medicenna 认为，这些数据证实了 MDNA11 在先前多个疗法均失败的晚期实体瘤患者中具有差异化且前景光明的治疗活性、安全性、PD 和 PK 特征
TORONTO and HOUSTON, April 09, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. ("Medicenna" or the "Company") (TSX: MDNA), a clinical-stage immunotherapy company focused on the development of Superkines, presented updated clinical results from the monotherapy dose escalation and ongoing expansion portions of the Phase 1/2 ABILITY-1 (A Beta-only IL-2 ImmunoTherapY) study evaluating MDNA11, a long-acting 'beta-enhanced not-alpha' interleukin-2 (IL-2) super-agonist, in patients with advanced solid tumors, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR) held in San Diego, CA, on April 9th, 2024.
多伦多和休斯顿，2024年4月9日（GLOBE NEWSWIRE）——专注于开发Superkines的临床阶段免疫疗法公司Medicenna Therapeutics Corp.（“MDNA” 或 “公司”）（多伦多证券交易所股票代码：MDNA）公布了评估长效 MDNA11 的1/2期 ABILITY-1（纯β免疫疗法）研究中单一疗法剂量增加和持续扩展部分的最新临床结果在美国协会2024年年会上，用于晚期实体瘤患者的 “β-增强型非α型” 白介素-2（IL-2）超级激动剂for Cancer Research (AACR) 于 2024 年 4 月 9 日在加利福尼亚州圣地亚哥举行。
"Although early, we have been impressed with MDNA11's single agent activity demonstrating a response rate of 29% and clinical benefit rate of 50% in patients with advanced solid tumors who have all failed prior immunotherapies," said Fahar Merchant, Ph.D., President and Chief Executive Officer of Medicenna. "We are very encouraged by a new partial response in a 85 year-old MSI-High patient with small bowel cancer and are particularly pleased with 100% reduction of all baseline target lesions in two of the four partial responders which includes a pancreatic cancer and a melanoma patient. MDNA11 continues to demonstrate its best-in-class potential. To further expedite the study, new sites in the US and Korea have started enrolment in the ongoing monotherapy expansion and combination escalation arms of the ABILITY-1 study as we look forward to reporting additional data at a medical conference in the first half of 2024."
Medicenna总裁兼首席执行官Fahar Merchant博士表示：“尽管很早，但MDNA11 的单一药物活性给我们留下了深刻的印象，该活性表明，先前免疫疗法均失败的晚期实体瘤患者的反应率为29％，临床获益率为50％。”“我们对一名85岁的MSI-High小肠癌患者出现新的部分反应感到非常鼓舞，特别高兴的是，包括一名胰腺癌和一名黑色素瘤患者在内的四名部分反应者中有两位的基线目标病变减少了100％。MDNA11 继续展现出其一流的潜力。为了进一步加快这项研究，美国和韩国的新研究中心已开始报名正在进行的 ABILITY-1 研究的单一疗法扩展和组合升级分组，因为我们期待在 2024 年上半年的医学会议上报告更多数据。”
Key findings from the monotherapy dose escalation and ongoing expansion portions of the ABILITY-1 study at the time of data cut-off (i.e. March 22, 2024) include:
在数据截止时（即 2024 年 3 月 22 日），ABILITY-1 研究的单一疗法剂量增加和持续扩展部分的主要发现包括：
Acceptable safety profile: No dose limiting toxicity (DLT) reported and no evidence of vascular leak syndrome (VLS). The vast majority (95%) of treatment-related adverse events (TRAEs) were of grade 1-2 and resolved within 48 hours; grade 3 TRAEs mainly constituted asymptomatic transient LFT elevations; no grade 4 or 5 events were reported.
可接受的安全概况：未报告剂量限制毒性（DLT），也没有血管渗漏综合征（VLS）的证据。绝大多数（95%）与治疗相关的不良事件（TRAE）为1-2级，并在48小时内消退；3级TRAE主要构成无症状的短暂性LFT升高；未报告4级或5级事件。
Encouraging single-agent anti-tumor activity at doses of ≥ 60 μg/kg in phase 2 eligible patients (N=14) who were all resistant to immune checkpoint inhibitors:
鼓励对免疫检查点抑制剂均具有耐药性的2期合格患者（N=14）在剂量≥60 μg/kg时具有单药抗肿瘤活性：
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Partial response reported for four patients with aggressive tumor types who had progressed on prior checkpoint inhibitors:
A pancreatic ductal adenocarcinoma (MSI-H) patient with primary resistance to pembrolizumab who was treated with MDNA11 (60 μg/kg) showed 100% resolution of all baseline lesions at week 66. A new lymph node lesion developed during a 8-week MDNA11 treatment break (vacation) was treated with a single course of radiotherapy prior to resumption of MDNA11. All baseline lesions remained completely resolved and the new lymph node lesion was <10 mm (considered physiological per RECIST v1.1), and MDNA11 treatment ended at week 90 while follow-up continues.
A patient with cutaneous melanoma progressed on dual checkpoint inhibitors, was treated with MDNA11 (90 μg/kg), and showed 100% resolution of the target lesion at weeks 28 and 36 with continuing reduction of the non-target lesions. Patient remains on MDNA11 treatment.
A second checkpoint-resistant cutaneous melanoma patient (nivolumab & rechallenge) showed partial response on MDNA11 (90 μg/kg) with a 31.25% reduction of target lesion at week 12 following pseudo-progression at week 8. A new lymph node lesion developed at week 16 while baseline target and non-target lesions remained stable or decreased. Patient remains on MDNA11 treatment.
An 85-year-old small bowel cancer (MSI-H) patient with secondary resistance to pembrolizumab showed partial response on MDNA11 (90 μg/kg) at week 20 with 37% reduction in target lesions. Patient remains on MDNA11 treatment.
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Durable stable disease (SD) for ≥ 24 weeks with shrinkage of target lesions observed in three metastatic melanoma patients:
Two patients (acral and cutaneous) with SD for >24 weeks on MDNA11 (120 μg/kg).
A third patient (cutaneous) with SD for > 1.5 years started on MDNA11 at 10 μg/kg dose and was subsequently dose escalated to 30, 60 and 90 μg/kg.
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四名先前使用检查点抑制剂后进展的侵袭性肿瘤类型患者报告了部分反应：
一名接受了 MDNA11（60 μg/kg）治疗的对派姆珠单抗有初级耐药性的胰腺导管腺癌（MSI-H）患者在第 66 周显示所有基线病变的缓解率为 100%。在为期 8 周的 MDNA11 治疗中断（休假）期间出现的新淋巴结病变在恢复 MDNA11 之前通过单个疗程的放射疗法进行治疗。所有基线病变仍完全消退，新的淋巴结病变
一名皮肤黑色素瘤患者在使用双检查点抑制剂时取得进展，接受了 MDNA11（90 μg/kg）的治疗，在第 28 周和第 36 周表现出目标病变的 100% 清晰度，非靶损持续减少。患者仍在接受 MDNA11 治疗。
第二名耐检查点皮肤黑色素瘤患者（nivolumab & rechallenge）在 MDNA11（90 μg/kg）上表现出部分反应，在第 8 周假性进展后，第 12 周目标病变减少了 31.25%。在第 16 周出现新的淋巴结病变，而基线靶和非靶损保持稳定或减少。患者仍在接受 MDNA11 治疗。
一名对pembrolizumab具有继发耐药性的85岁小肠癌（MSI-H）患者在第20周对 MDNA11（90 μg/kg）表现出部分反应，目标病变减少了37％。患者仍在接受 MDNA11 治疗。
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在三名转移性黑色素瘤患者中观察到的持续稳定疾病（SD）持续时间≥ 24 周，目标病变萎缩：
两名患者（肢端和皮肤）服用 MDNA11（120 微克/千克）的 SD 持续时间超过 24 周。
第三名患有 SD 超过 1.5 年的患者（皮肤）开始服用 MDNA11，剂量为 10 μg/kg，随后剂量增加到 30、60 和 90 μg/kg。
MDNA11 continues to exhibit potent effector immune profile with sustained peripheral expansion of cytotoxic CD4+ T, CD8+ T and NK cells with minimal impact on immunosuppressive Tregs. CD8/Treg ratio and activation markers (CD25+ and OX40+) showed peak increase in CD8+ T cells at the Recommended Dose for Expansion (RDE, 90 μg/kg Q2W IV). OX40 on Tregs also peaked at the RDE but in contrast to CD8+ T cells, it leads to impairment of their immune suppressive function.
MDNA11 继续表现出强大的效应免疫特征，细胞毒性 CD4+ T、CD8+ T 和 NK 细胞的外周持续扩张，对免疫抑制性 Treg 的影响微乎其微。CD8/Treg 比率和活化标志物（CD25+ 和 OX40+）显示，在推荐扩张剂量（RDE，90 μg/kg Q2W IV）下，CD8+ T 细胞的峰值升高。Tregs上的OX40在RDE时也达到了峰值，但与CD8+ T细胞形成鲜明对比的是，它会导致其免疫抑制功能受损。
Monotherapy expansion is continuing to enroll patients with metastatic melanoma, non-melanoma skin cancers (cSCC, MCC, and BCC) and MSI-H/dMMR tumors. Combination dose escalation has also commenced.
单一疗法的扩张正在继续招收转移性黑色素瘤、非黑色素瘤皮肤癌（cSCC、MCC和BCC）和MSI-H/DMMR肿瘤的患者。联合剂量增加也已开始。
A copy of the poster and a related slide deck have been posted to the "Scientific Presentations" page of Medicenna's website.
海报的副本和相关的幻灯片已发布到Medicenna网站的 “科学演讲” 页面上。
About MDNA11
关于 MDNA11
MDNA11 is a long-acting 'beta-enhanced not-alpha' interleukin-2 (IL-2) Superkine specifically engineered to overcome the shortcomings of aldesleukin and other next generation IL-2 variants by preferentially activating immune effector cells (CD4+ T, CD8+ T and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. These unique proprietary features of the IL-2 Superkine have been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic (PK) profile and pharmacological activity of MDNA11 due to albumin's natural propensity to accumulate in highly vascularized sites, in particular tumor and tumor draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both a monotherapy and in combination with pembrolizumab (Keytruda).
MDNA11 是一种长效 “β-增强型非 α” 白介素-2 (IL-2) Superkine，专门设计用于通过优先激活负责杀死癌细胞的免疫效应细胞（CD4+ T、CD8+ T 和 NK 细胞）来克服aldesleukin和其他下一代IL-2变体的缺点，同时尽量减少或不刺激免疫抑制性Tregs。IL-2 Superkine 的这些独特专有特性是通过整合七种特定突变并将其基因融合到重组人白蛋白支架中来改善 MDNA11 的药代动力学 (PK) 特征和药理活性来实现的，因为白蛋白自然倾向于在高度血管化的部位积聚，尤其是肿瘤和肿瘤排出的淋巴结。在 ABILITY-1 的1/2期研究中，目前正在对 MDNA11 进行评估，该研究既是单一疗法，又是与pembrolizumab（Keytruda）联合使用。