美通社

2024-12-13 08:00

Transcenta Debuts Promising Anti-Tumor Activity of Novel LIV-1 Targeting ADCs with Site-Specific Conjugated Topo I Inhibitor Payload in TNBC Tumor Models at 2024 SABCS

PRINCETON, N.J. and SUZHOU, China, Dec. 13, 2024 /PRNewswire/ -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a global clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, announced late-breaking presentation of preclinical study results of novel humanized LIV-1 antibody based ADCs at 2024 San Antonio Breast Cancer Symposium (SABCS). The ADCs (ADC-1 and ADC-2) were engineered using Transcenta's proprietary antibody with site-specifical conjugation of Topoisomerase I Inhibitor payloads and these ADCs demonstrated significantly higher tumor regression activities than MMAE based ADCs in triple-negative breast cancer (TNBC) tumor models.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, the responses are typically short lived. Thus, there is an urgent need to develop more effective treatments [1].

LIV-1, a member of the zinc transporter family and an estrogen-regulated gene in metastatic breast cancer, is overexpressed in a high prevalence in breast cancer (93%), including both TNBC and hormone receptor positive breast cancer, as well as in melanoma (82%), prostate (72%), ovarian (48%) and uterine (30%) cancer. This makes LIV-1 an attractive cell surface target for developing ADC therapeutics.

To develop next generation LIV-1 targeting ADC, Transcenta generated a proprietary novel humanized anti-LIV-1 mAb, 48D6, which displayed unique epitope form benchmark antibody, high binding affinity, specificity, excellent internalization ability. The conjugation method also eliminated FcR binding which resulted in significantly reduced non-specific FcR mediated binding and clearance, and improved pharmacokinetics profile in mice.

In vitro studies indicated that breast tumor cells, such as MDA-MB-468 and MCF-7, are more sensitive to Topo I inhibitor than MMAE. Consequently, Transcenta developed two Topo I inhibitor-based ADCs (ADC-1 and ADC-2) using glycotransferase mediated site-specific conjugation. Both ADC-1 and ADC-2 have a drug-to-antibody ratio (DAR) of 4 but with two different Topo I inhibitor payloads. A MMAE based ADC (ADC-3) with the same site-specific conjugation and DAR4 was also synthesized as the control.

Although ADC-1 and ADC-2 displayed similar and specific cytotoxic activities against human LIV-1-expressing tumor cells in vitro, as compared to SGN-LIV1A analog (DAR4) or ADC-3, they exhibited much higher maximal tumor cell killing than SGN-LIV1A analog in vivo. In addition, both ADC-1 and ADC-2 demonstrated a strong bystander effect which is important to overcome tumor heterogeneity.

In vivo pharmacology study revealed that ADC-1 or ADC-2 exhibited dose-dependent and more potent anti-tumor activities than the SGN-LIV1A analog or ADC-3 in the human LIV-1 transfected MDA-MB-468, a TNBC tumor model.

At 3 mg/kg the tumor growth inhibition (TGI)% were: ADC-1 92.4%, ADC-2 94.7%, ADC-3 68.5% and SGN-LIV1A analog 57.0% on Day 30. However, the overall response rate (ORR, 50% reduction of tumor volume from baseline) at 3mg/kg for SGN-LIV1A analog or ADC-3 was 0%, while ORRs of ADC-1 and ADC-2 were 40% and 70%, respectively. At 6 mg/kg, on Day 42, ORRs of ADC-1 and ADC-2 were 90% and 100%, respectively, and complete response (CR) rates were 90% and 100% respectively. The body weight of mice didn't change significantly at either 3 or 6 mg/kg for ADC-1 or ADC-2.

"The significantly enhanced anti-tumor activities of ADC-1 and ADC-2 are likely due to the high affinity binding of 48D6 to LIV-1 and the high cytotoxicity of Topo I inhibitor for breast tumor cells." said Dr. Xueming Qian, Chairman of the Board and CEO at Transcenta, "These data warrant further investigation of the lead LIV-1 targeting ADCs (ADC-1 and ADC-2) as potential next-generation therapeutic agent in LIV-1 positive breast cancer and other solid tumors."

The 47th San Antonio Breast Cancer Symposium (SABCS) held from December 10 to 13, 2024, in San Antonio, Texas, USA. This Symposium is designed to provide state-of-the-art information on the experimental biology, etiology, prevention, diagnosis, and therapy of breast cancer and premalignant breast disease to an international audience of academic and private physicians and researchers.

About Transcenta

Transcenta (HKEX: 06628) is a clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing.

Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Princeton, US and in Beijing, Shanghai and Guangzhou of China, and External Partnering Center in Boston and Los Angeles, US. Transcenta is developing 14 therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders.

Media contact: Bryan Cheng, bryan.cheng@transcenta.com

source: Transcenta Holding Limited

《說說心理話》親友自殺離世遺屬如何自處?身邊親友應該怎樣陪他們走出人生最低谷?► 即睇

人氣文章
最近7天
1
港股 | 蕭猷華:內地AI發展迅速,阿里巴巴股價看俏
2
高息定存 | 一周高息合集,銀行高息搶存,富邦1個月4.88厘,華僑1年期3.6厘
3
PapaHome淘寶家具實體店22日開幕,選址尖沙咀中港城,料創100個就業機會
4
高息定存 | 華僑銀行推新春港元定存優惠,88天或188天享3.68厘
5
英偉達 | DeepSeek衝擊AI晶片行業結構 英偉達暴跌仍未急抄底
6
高息定存 | 一周高息合集,蛇年定存金蛇起舞,1個月定存高達8厘
7
啟德體育園明天足球賽測試,4.4萬公僕參與涉逾400萬車馬費
8
電騙 | 黃俊碩:多管齊下,防治內地留學生受騙
9
環球央行 | 歐洲央行宣布再次減息0.25厘,符合市場預期
10
一本萬利 | 2025年的五個「勿」(有片)
11
易經看世界 | 乙巳蛇年趨吉五招:言行注意甚麼?應遠離甚麼人?(有片)
12
專訪 | 關稅戰 | 香港物流協會副會長梁庭彰:美物流商停收包裹對跨境電商打擊重大
13
高息定存 | 一周高息合集,減息預期降溫,銀行3個月最高5.68厘,6個月3.55厘
14
港股 | 午市前瞻 | iPhone SE難救中國市場 專家提醒比電已超買
15
【FOCUS】螺絲殼裏做道場,DeepSeek致勝啟示
16
大S | 台灣藝人徐熙媛因流感併發肺炎逝世,享年48歲
17
DeepSeek推出即上蘋果中國區榜首,能力直追OpenAI
18
【FOCUS】悟空、哪吒、DeepSeek,如何啟示香港
19
日入而息 | 習近平據報下周見科企領袖,證監會審視8券商孖展風控,大酒店轉蝕9億
20
收市短打 | 楊韻銳:港股升勢有成交配合 惟留意關鍵阻力位!
21
新世界 | 摩通:新世界若債務違約或打開行業「潘朵拉盒子」
22
港股 | 午市前瞻 | AI應用概念炒作有錢途 下階段部署邊隻好?
23
【FOCUS】侵侵呼籲全球「降息」,日銀祭18年最激進加息
24
彭博亞洲20大富裕家族,香港5大家族上榜,新地郭氏排名最高,無李嘉誠李兆基?
25
港股 | 蕭猷華:春節假後,恒指逐步上望21000點
26
高息定存 | 信銀國際12個月港元定存高達3.5厘
27
神州經脈 | 特朗普或與華討論關稅,人民幣大漲,滬指連升兩周
28
David Webb:因病情惡化,將有序結束個人財經網站
29
民營企業座談會 | 習近平在京出席民營企業座談會
30
AI | 蔡崇信確認阿里與蘋果合作,撰文談DeepSeek崛起帶來兩大啟示
專業版
HV2
精裝版
SV2
串流版
IQ 登入
強化版
TQ
強化版
MQ

etnet榮膺「第九屆傳媒轉型大獎」四大獎項

【限時優惠$68/月】申請etnet強化版MQ手機串流報價服務 捕捉板塊輪動,提高獲利勝算

etnet榮獲HKEX Awards 2023 「最佳證券數據供應商」大獎

大國博弈

2025-26年度財政預算案

貨幣攻略

說說心理話

Watch Trends 2024

北上食買玩

Art Month 2024

理財秘笈

流感高峰期

山今養生智慧

輕鬆護老