Last update 01 Nov 2024

Apc-001

Last update 01 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Aptamer drug conjugates

Synonyms

Apc001PE, DNA, (Cm-Gm-Gm-Gm-G-T-G-T-G-G-G-T-T-C-G-T-C-G-T-T-A-G-C-T-T-G-A-T-T-T-G-G-C-A-G-C-Um-Gm-Cm-Cm-(3'¿3')-dT), 5'-ester with [[5-(phosphoonoxy) pentyl] amino] carbonyl-oxy-1, 2-ethanediyl, sodium salt, PEG40k conjugated Apc001

+ [2]

Target

SOST

Mechanism

SOST inhibitors(Sclerostin inhibitors)

Therapeutic Areas

NeoplasmsCongenital DisordersEndocrinology and Metabolic Disease+ [3]

Active Indication

Diabetes Mellitus, Type 2Familial Hypophosphatemic RicketsOsteogenesis Imperfecta+ [2]

Inactive Indication-

Originator Organization

Aptacure Therapeutics Ltd.

Hong Kong Baptist University

Active Organization

Aptacure Therapeutics Ltd.

Hong Kong Baptist University

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

RegulationOrphan Drug (US)

Structure

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100 Clinical Results associated with Apc-001

100 Translational Medicine associated with Apc-001

100 Patents (Medical) associated with Apc-001

Literatures (Medical) associated with Apc-001

01 Dec 2023·Molecular Therapy - Nucleic Acids

A bimolecular modification strategy for developing long-lasting bone anabolic aptamer

Article

Author: Ma, Yuan ; Ni, Shuaijian ; Gubu, Amu ; Wang, Luyao ; Li, Haitian ; Zhang, Huarui ; Lyu, Aiping ; Zhang, Yihao ; Zhang, Ge ; Yu, Yuanyuan ; Zhang, Baoting ; Zhang, Zongkang ; Wang, Yuzhe ; Yu, Sifan

The molecular weight of nucleic acid aptamers (20 kDa) is lower than the cutoff threshold of the renal filtration (30-50 kDa), resulting in a very short half-life, which dramatically limits their druggability. To address this, we utilized 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-(4-hydroxy-2-oxo-2H-chromen-6-yl)propenamide (HC) and 12-((2,5-dioxopyrrolidin-1-yl)oxy)-12-oxododecanoic acid (DA), two newly designed coupling agents, for synergistic binding to human serum albumin (HSA). Both HC and DA are conjugated to a bone anabolic aptamer (Apc001) against sclerostin to form an Apc001OC conjugate with high binding affinity to HSA. Notably, HC and DA could synergistically facilitate prolonging the half-life of the conjugated Apc001 and promoting its bone anabolic potential. Using the designed blocking peptides, the mechanism studies indicate that the synergistic effect of HC-DA on pharmacokinetics and bone anabolic potential of the conjugated Apc001 is achieved via their synergistic binding to HSA. Moreover, biweekly Apc001OC at 50 mg/kg shows comparable bone anabolic potential to the marketed sclerostin antibody given weekly at 25 mg/kg. This proposed bimolecular modification strategy could help address the druggability challenge for aptamers with a short half-life.

01 Jan 2022·Theranostics

Therapeutic aptamer targeting sclerostin loop3 for promoting bone formation without increasing cardiovascular risk in osteogenesis imperfecta mice

Article

Author: Zhuo, Zhenjian ; Zhang, Shu ; Zhang, Ning ; Zhang, Zhenlin ; Chu, Hang Yin ; Zhang, Zong-Kang ; Li, Mei ; Li, Dijie ; Yu, Yuanyuan ; Xie, Duoli ; Pan, Xiaohua ; Zhong, Chuanxin ; Ren, Qing ; Xia, Weibo ; Ni, Shuaijian ; Wang, Luyao ; Shang, Peng ; Lu, Aiping ; Zhang, Ge ; Zhang, Bao-Ting ; Chen, Lin ; Sun, Meiheng ; Liu, Jin ; Li, Nanxi ; Zhang, Huarui

Rationale: Sclerostin inhibition demonstrated bone anabolic potential in osteogenesis imperfecta (OI) mice, whereas humanized therapeutic sclerostin antibody romosozumab for postmenopausal osteoporosis imposed clinically severe cardiac ischemic events. Therefore, it is desirable to develop the next generation sclerostin inhibitors to promote bone formation without increasing cardiovascular risk for OI. Methods and Results: Our data showed that sclerostin suppressed inflammatory responses, prevented aortic aneurysm (AA) and atherosclerosis progression in hSOST^ki.Col1a2^+/G610C.ApoE^-/- mice. Either loop2&3 deficiency or inhibition attenuated sclerostin's suppressive effects on expression of inflammatory cytokines and chemokines in vitro, whilst loop3 deficiency maintained the protective effect of sclerostin on cardiovascular system both in vitro and in vivo. Moreover, loop3 was critical for sclerostin's antagonistic effect on bone formation in Col1a2^+/G610C mice. Accordingly, a sclerostin loop3-specific aptamer aptscl56 was identified by our lab. It could recognize both recombinant sclerostin and sclerostin in the serum of OI patients via targeting loop3. PEG40k conjugated aptscl56 (Apc001PE) demonstrated to promote bone formation, increase bone mass and improve bone microarchitecture integrity in Col1a2^+/G610C mice via targeting loop3, while did not show influence in inflammatory response, AA and atherosclerosis progression in Col1a2^+/G610C.ApoE^-/- mice with Angiotensin II infusion. Further, Apc001PE had no influence in the protective effect of sclerostin on cardiovascular system in hSOST^ki.Col1a2^+/G610C.ApoE^-/- mice, while it inhibited the antagonistic effect of sclerostin on bone formation in hSOST^ki.Col1a2^+/G610C mice via targeting loop3. Apc001PE was non-toxic to healthy rodents, even at ultrahigh dose. Apc001PE for OI was granted orphan drug designation by US-FDA in 2019 (DRU-2019-6966). Conclusion: Sclerostin loop3-specific aptamer Apc001PE promoted bone formation without increasing cardiovascular risk in OI mice.

Nature CommunicationsQ1 · CROSS-FIELD

Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation

Q1 · CROSS-FIELD

ArticleOA

Author: Zhong, Chuanxin ; Li, Mei ; Ren, Qing ; Zhang, Shu ; Zhang, Huarui ; Xia, Weibo ; Zhang, Bao-Ting ; Wang, Luyao ; Zhang, Ning ; Li, Dijie ; Chu, Hang Yin ; Yu, Yuanyuan ; Zhang, Zhenlin ; Li, Yongshu ; Chen, Lin ; Zhang, Zong-Kang ; Liu, Jin ; Lu, Aiping ; Xie, Duoli ; Ni, Shuaijian ; Pan, Xiaohua ; Zhuo, Zhenjian ; Li, Nanxi ; Zhang, Ge ; Sun, Meiheng

AbstractSclerostin negatively regulates bone formation by antagonizing Wnt signalling. An antibody targeting sclerostin for the treatment of postmenopausal osteoporosis was approved by the U.S. Food and Drug Administration, with a boxed warning for cardiovascular risk. Here we demonstrate that sclerostin participates in protecting cardiovascular system and inhibiting bone formation via different loops. Loop3 deficiency by genetic truncation could maintain sclerostin’s protective effect on the cardiovascular system while attenuating its inhibitory effect on bone formation. We identify an aptamer, named aptscl56, which specifically targets sclerostin loop3 and use a modified aptscl56 version, called Apc001PE, as specific in vivo pharmacologic tool to validate the above effect of loop3. Apc001PE has no effect on aortic aneurysm and atherosclerotic development in ApoE−/− mice and hSOSTki.ApoE−/− mice with angiotensin II infusion. Apc001PE can promote bone formation in hSOSTki mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation.

100 Deals associated with Apc-001

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Preclinical	HK	Aptacure Therapeutics Ltd.	30 Jan 2022
Familial Hypophosphatemic Rickets	Preclinical	HK	Aptacure Therapeutics Ltd.	30 Jan 2022
Familial Hypophosphatemic Rickets	Preclinical	US	Aptacure Therapeutics Ltd.	30 Jan 2022
Osteogenesis Imperfecta	Preclinical	HK	Aptacure Therapeutics Ltd.	30 Jan 2022
Osteoporosis	Preclinical	HK	Aptacure Therapeutics Ltd.	30 Jan 2022
Triple Negative Breast Cancer	Preclinical	HK	Aptacure Therapeutics Ltd.	30 Jan 2022

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Apc-001

Overview

Basic Info

Structure

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R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation