First in Human, Phase Ia/Ib Study for Safety, Tolerability, Pharmacokinetics, and Clinical Activity Evaluation of ADEL-Y01 in Healthy Participants and in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease

This is a Phase Ia/Ib, two-part, randomized, placebo-controlled, double-blinded, first in human(FIH) study to evaluate the safety, tolerability, PK, and PD of ADEL-Y01 in healthy participants in Part 1 and participants with MCI due to AD and mild AD in Part 2. The study includes 2 parts: Part 1 (single ascending dose [SAD] and Part 2 (multiple ascending dose [MAD]).

Start Date06 Feb 2024

Sponsor / Collaborator

ADEL, Inc.

[+1]

100 Clinical Results associated with ADEL, Inc.

0 Patents (Medical) associated with ADEL, Inc.

Literatures (Medical) associated with ADEL, Inc.

01 Nov 2023·Molecular Psychiatry

Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse

Article

Author: Kim, Min-Seok ; Song, Youngsup ; Yoon, Seung-Yong ; Sung, Young Hoon ; Kang, Young-Ho ; Park, Sukyoung ; Heo, Hwon ; Park, Ji-Seon ; Kim, Je Seong ; Kim, Ki-Hyun ; Shim, Woo Hyun ; Kim, Dong-Hou ; Lee, Seung-Eun

AbstractSocial hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.

17 Apr 2023·The Journal of clinical investigation

Monoclonal antibody Y01 prevents tauopathy progression induced by lysine 280-acetylated tau in cell and mouse models.

Article

Author: Na, Duk L ; Lee, Kyoung-Hye ; Jang, Hyemin ; Kim, Dong-Hou ; Kim, Na-Young ; Lee, Se-Jong ; Park, Jaewan ; Yoon, Seung-Yong ; Mun, Yeon-Seon ; Song, Ha-Lim ; Cho, Kwangmin ; Shim, Young-Lim ; Kim, Meong Il ; Pack, Chan-Gi ; Hong, Minsun ; Song, Jung-A ; Jung, Minkyo ; Kim, Min-Seok ; Jeon, Yu-Na

The spatiotemporal pattern of the spread of pathologically modified tau through brain regions in Alzheimer's disease (AD) can be explained by prion-like cell-to-cell seeding and propagation of misfolded tau aggregates. Hence, to develop targeted therapeutic antibodies, it is important to identify the seeding- and propagation-competent tau species. The hexapeptide 275VQIINK280 of tau is a critical region for tau aggregation, and K280 is acetylated in various tauopathies, including AD. However, the mechanism that links tau acetylated on lysine 280 (tau-acK280) to subsequent progression to neurodegenerative disease remains unclear. Here, we demonstrate that tau-acK280 is critical for tau propagation processes including secretion, aggregation, and seeding. We developed an antibody, Y01, that specifically targets tau-acK280 and solved the crystal structure of Y01 in complex with an acK280 peptide. The structure confirmed that Y01 directly recognizes acK280 and the surrounding residues. Strikingly, upon interaction with acetylated tau aggregates, Y01 prevented tauopathy progression and increased neuronal viability in neuron cultures and in tau-Tg mice through antibody-mediated neutralization and phagocytosis, respectively. Based on our observations that tau-acK280 is a core species involved in seeding and propagation activities, the Y01 antibody that specifically recognizes acK280 represents a promising therapeutic candidate for AD and other neurodegenerative diseases associated with tauopathy.

Cell & Bioscience

Neuronal MHC-I complex is destabilized by amyloid-β and its implications in Alzheimer's disease

Author: Cho, Kwangmin ; Cho, Mi-Hyang ; Kim, Kyunggon ; Yoon, Seung-Yong ; Kim, Na-Young ; Kim, Min-Seok ; Kim, Dong-Hou

The expression of major histocompatibility complex I (MHC-I) in neurons has recently been shown to regulate neurite outgrowth and synaptic plasticity.However, its contribution to neurodegenerative diseases such as Alzheimer's disease (AD) remains largely unknown.In this study, we investigated the relationship between impaired MHC-I-β2M complex and AD in vitro and human AD samples.Interaction between protein was identified by liquid chromatog.-tandem mass spectrometry and confirmed by immunoprecipitationSingle-chain trimer of MHC-I-β2M was generated to study the effect of stabilization of MHC-I-β2M complex on NCAM1 signaling.MHC-I is destabilized in the brains of AD patients and neuronal cells treated with oligomeric β-amyloid (Aβ).Specifically, Aβ oligomers disassemble the MHC-I-β2-microglobulin (β2M) complex, leading to reduced interactions with neural cell adhesion mol. 1 (NCAM1), a novel interactor of neuronal MHC-I, and decreased signaling.Inhibition of MHC-I-β2M complex destabilization by non-dissociable MHC-I-β2M-peptide complex restored MHC-I-NCAM1 signaling in neuronal cells.The current study demonstrated that disruption of MHC-1-NCAM1 signaling by Aβ induced disassembly of MHC-I-β2M complex is involved in the pathophysiol. of AD.Moreover, our findings suggest modulation of MHC-I stability may be a potential therapeutic target for restoring synaptic function in AD.

News (Medical) associated with ADEL, Inc.

23 Feb 2024

·www.prnewswire.com

Oscotec/ADEL Initiates First-in-Human Dosing in Ph1 of Anti-MTBR Tau Antibody ADEL-Y01 In Alzheimer's Disease

PANGYO, South Korea, Feb. 23, 2024 /PRNewswire/ -- Oscotec Inc. and ADEL Inc. announced the dosing of the first healthy participant in its first-in-human study of ADEL-Y01 for the treatment of Alzheimer's disease (AD). Oscotec and ADEL are jointly developing a novel disease-modifying immunotherapy agent (ADEL-Y01) targeting tau protein accumulation in the AD brain. ADEL-Y01 is uniquely designed to target tau protein acetylated at lysine-280 (acK280), inhibiting aggregation and propagation of toxic tau and thus may slow the course of the disease. This phase 1a/1b study in the U.S. is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of ADEL-Y01 in 40 healthy volunteers as well as in 33 participants with Mild Cognitive Impairment due to Alzheimer's disease or mild Alzheimer's disease. "Given that tau is strongly correlated with AD progression and clinical severity, targeting of tau is anticipated to effectively slow the disease progress. As our understanding of the pivotal role of the tau mid-region MTBR increases, selecting the right epitope becomes crucial in developing tau-targeting therapeutics to attain clinical benefits", explained SeungYong Yoon, MD/PhD, CEO of ADEL. "Oscotec is pleased to reach a significant milestone leading the clinical study as a co-developer with ADEL, and we will continue to bring innovative medicines in neurogenerative diseases", said Taeyoung Yoon, CEO of Oscotec. The preclinical results of ADEL-Y01 in animal models were published last year, demonstrating improvement in memory impairment, behavioral deficits through the inhibition of Tau seeding and propagation.("Monoclonal antibody Y01 prevents tauopathy progression induced by lysine 280–acetylated tau in cell and mouse models" in The Journal of Clinical Investigation 2023) About Oscotec Inc. Oscotec is a clinical stage drug discovery and development company pursuing translation of rigorous science into innovative medicine for clinically unmet needs.. The Company's clinical pipeline consists of targeted therapeutics in immunology and oncology. Oscotec is developing cevidoplenib (SYK inhibitor) for ITP (Phase 2, completed) and FLT3/AXL inhibitor for AML (Phase 1) as well as solid tumors (Phase 1). The company is also the originator of Lazertinib (LECLAZA®), a 3rd generation EGFR inhibitor being developed by Janssen Pharma and Yuhan Corp. for lung cancers. About ADEL Inc. ADEL is a leading company of cutting-edge technologies for the treatment and diagnosis of neurological diseases including Alzheimer's disease. Founded by scientists who have investigated Alzheimer's disease at Asan Medical Center, University of Ulsan College of Medicine, Korea, ADEL is developing smart, innovative drug candidates for the patients worldwide. Contacts Jihyun Park, IR/PR [email protected] Kyung Hoon Hwang, Research Director/COO [email protected] SOURCE Oscotec Inc.

Phase 2ImmunotherapyPhase 1

100 Deals associated with ADEL, Inc.

100 Translational Medicine associated with ADEL, Inc.

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The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Drug(Targets)	Indications	Global Highest Phase

ADEL-Y01 ( TAU )	Alzheimer Disease More	Phase 1
ADEL-Y04 ( apolipoprotein E4 )	Alzheimer Disease More	Preclinical
ADEL-Y03 ( B2M )	Fibrosis, Liver More	Preclinical
ADEL-Y07 ( AR x TAU )	Prostatic Cancer More	Discovery
ADEL-D01 ( TAU )	Alzheimer Disease More	Unknown

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