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 在美國癌症研究協會 (AACR) 2024 年年會上公佈了 1/2 期 ABILITY-1 研究劑量遞增和持續劑量擴大所產生的單劑 MDNA11 抗腫瘤活性的最新結果

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

Durable stable disease (SD) in 3 melanoma patients for 6 to 18 months with concomitant tumor shrinkage

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

MDNA11 is generally well tolerated with no dose-limiting toxicities or vascular leak syndrome reported in any of the dose escalation cohorts

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

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.

"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."

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:

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.

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:

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.
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.

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.

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.

A copy of the poster and a related slide deck have been posted to the "Scientific Presentations" page of Medicenna's website.

About 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).

迄今爲止，在4種局部反應（PR）中觀察到一例黑色素瘤和一名胰腺癌患者的目標病變減少了100％，其中包括4名可評估劑量擴展患者中的2名和2名MSI-H患者中的2例

3 名黑色素瘤患者持續6至18個月的持久穩定疾病（SD），伴隨腫瘤萎縮

隨着緩解率和臨床獲益率分別提高到 29% 和 50%（4 PR，3 SD），MDNA11 在 ABILITY-1 研究中繼續在檢查點抑制劑療法失敗的高劑量 2 期合格患者（N=14）中表現出令人信服的單藥活性

MDNA11 的耐受性通常良好，在任何劑量遞增隊列中均未報告劑量限制毒性或血管泄漏綜合徵

Medicenna 認爲，這些數據證實了 MDNA11 在先前多個療法均失敗的晚期實體瘤患者中具有差異化且前景光明的治療活性、安全性、PD 和 PK 特徵

多倫多和休斯頓，2024年4月9日（GLOBE NEWSWIRE）——專注於開發Superkines的臨床階段免疫療法公司Medicenna Therapeutics Corp.（“MDNA” 或 “公司”）（多倫多證券交易所股票代碼：MDNA）公佈了評估長效 MDNA11 的1/2期 ABILITY-1（純β免疫療法）研究中單一療法劑量增加和持續擴展部分的最新臨床結果在美國協會2024年年會上，用於晚期實體瘤患者的 “β-增強型非α型” 白介素-2（IL-2）超級激動劑for Cancer Research (AACR) 於 2024 年 4 月 9 日在加利福尼亞州聖地亞哥舉行。

Medicenna總裁兼首席執行官Fahar Merchant博士表示：“儘管很早，但MDNA11 的單一藥物活性給我們留下了深刻的印象，該活性表明，先前免疫療法均失敗的晚期實體瘤患者的反應率爲29％，臨床獲益率爲50％。”“我們對一名85歲的MSI-High小腸癌患者出現新的部分反應感到非常鼓舞，特別高興的是，包括一名胰腺癌和一名黑色素瘤患者在內的四名部分反應者中有兩位的基線目標病變減少了100％。MDNA11 繼續展現出其一流的潛力。爲了進一步加快這項研究，美國和韓國的新研究中心已開始報名正在進行的 ABILITY-1 研究的單一療法擴展和組合升級分組，因爲我們期待在 2024 年上半年的醫學會議上報告更多數據。”

在數據截止時（即 2024 年 3 月 22 日），ABILITY-1 研究的單一療法劑量增加和持續擴展部分的主要發現包括：

可接受的安全概況：未報告劑量限制毒性（DLT），也沒有血管滲漏綜合徵（VLS）的證據。絕大多數（95%）與治療相關的不良事件（TRAE）爲1-2級，並在48小時內消退；3級TRAE主要構成無症狀的短暫性LFT升高；未報告4級或5級事件。

鼓勵對免疫檢查點抑制劑均具有耐藥性的2期合格患者（N=14）在劑量≥60 μg/kg時具有單藥抗腫瘤活性：

四名先前使用檢查點抑制劑後進展的侵襲性腫瘤類型患者報告了部分反應：
- 一名接受了 MDNA11（60 μg/kg）治療的對派姆珠單抗有初級耐藥性的胰腺導管腺癌（MSI-H）患者在第 66 周顯示所有基線病變的緩解率爲 100%。在爲期 8 周的 MDNA11 治療中斷（休假）期間出現的新淋巴結病變在恢復 MDNA11 之前通過單個療程的放射療法進行治療。所有基線病變仍完全消退，新的淋巴結病變<10 mm（根據 RECIST v1.1 視爲生理病變），MDNA11 治療於第 90 周結束，隨訪仍在繼續。
- 一名皮膚黑色素瘤患者在使用雙檢查點抑制劑時取得進展，接受了 MDNA11（90 μg/kg）的治療，在第 28 周和第 36 周表現出目標病變的 100% 清晰度，非靶損持續減少。患者仍在接受 MDNA11 治療。
- 第二名耐檢查點皮膚黑色素瘤患者（nivolumab & rechallenge）在 MDNA11（90 μg/kg）上表現出部分反應，在第 8 周假性進展後，第 12 周目標病變減少了 31.25%。在第 16 周出現新的淋巴結病變，而基線靶和非靶損保持穩定或減少。患者仍在接受 MDNA11 治療。
- 一名對pembrolizumab具有繼發耐藥性的85歲小腸癌（MSI-H）患者在第20周對 MDNA11（90 μg/kg）表現出部分反應，目標病變減少了37％。患者仍在接受 MDNA11 治療。
在三名轉移性黑色素瘤患者中觀察到的持續穩定疾病（SD）持續時間≥ 24 周，目標病變萎縮：
- 兩名患者（肢端和皮膚）服用 MDNA11（120 微克/千克）的 SD 持續時間超過 24 周。
- 第三名患有 SD 超過 1.5 年的患者（皮膚）開始服用 MDNA11，劑量爲 10 μg/kg，隨後劑量增加到 30、60 和 90 μg/kg。

MDNA11 繼續表現出強大的效應免疫特徵，細胞毒性 CD4+ T、CD8+ T 和 NK 細胞的外周持續擴張，對免疫抑制性 Treg 的影響微乎其微。CD8/Treg 比率和活化標誌物（CD25+ 和 OX40+）顯示，在推薦擴張劑量（RDE，90 μg/kg Q2W IV）下，CD8+ T 細胞的峯值升高。Tregs上的OX40在RDE時也達到了峯值，但與CD8+ T細胞形成鮮明對比的是，它會導致其免疫抑制功能受損。

單一療法的擴張正在繼續招收轉移性黑色素瘤、非黑色素瘤皮膚癌（cSCC、MCC和BCC）和MSI-H/DMMR腫瘤的患者。聯合劑量增加也已開始。

海報的副本和相關的幻燈片已發佈到Medicenna網站的 “科學演講” 頁面上。

關於 MDNA11

MDNA11 是一種長效 “β-增強型非 α” 白介素-2 (IL-2) Superkine，專門設計用於通過優先激活負責殺死癌細胞的免疫效應細胞（CD4+ T、CD8+ T 和 NK 細胞）來克服aldesleukin和其他下一代IL-2變體的缺點，同時儘量減少或不刺激免疫抑制性Tregs。IL-2 Superkine 的這些獨特專有特性是通過整合七種特定突變並將其基因融合到重組人白蛋白支架中來改善 MDNA11 的藥代動力學 (PK) 特徵和藥理活性來實現的，因爲白蛋白自然傾向於在高度血管化的部位積聚，尤其是腫瘤和腫瘤排出的淋巴結。在 ABILITY-1 的1/2期研究中，目前正在對 MDNA11 進行評估，該研究既是單一療法，又是與pembrolizumab（Keytruda）聯合使用。

譯文內容由第三人軟體翻譯。

以上內容僅用作資訊或教育之目的，不構成與富途相關的任何投資建議。富途竭力但無法保證上述全部內容的真實性、準確性和原創性。

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)

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