Delving into the Latest Updates on KANAPH Therapeutics, Inc. with Synapse

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疾病领域	数量

肿瘤	10
内分泌与代谢疾病	2
神经系统疾病	2

排名前五的药物类型	数量

小分子化药	4
融合蛋白	2
双特异性抗体	2
化学药	2
ADC	1

排名前五的靶点	数量

SHP2(蛋白酪氨酸磷酸酶-2)	3
FAP(成纤维细胞激活蛋白α)	2
SOS1(SOS1蛋白质)	1
IL-12(白细胞介素-12)	1
EGFR C797S(表皮生长因子受体erbB1 C797S)	1

关联

16

项与 KANAPH Therapeutics, Inc. 相关的药物

KNP-101

靶点

IL-12

作用机制

IL-12替代物

在研机构

KANAPH Therapeutics, Inc.初创企业

原研机构

KANAPH Therapeutics, Inc.初创企业

在研适应症

实体瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

KNP-503

靶点

SHP2

作用机制

SHP2抑制剂

在研机构

KANAPH Therapeutics, Inc.初创企业

原研机构

KANAPH Therapeutics, Inc.初创企业

在研适应症

结直肠癌 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

CYRS-1645

SOS1抑制剂(kanaph Therapeutics)

靶点

SOS1

作用机制

SOS1抑制剂

在研机构

KANAPH Therapeutics, Inc.初创企业 [+1]

原研机构

Cyrus Therapeutics, Inc.初创企业

在研适应症

结直肠癌 [+3]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 KANAPH Therapeutics, Inc. 相关的临床结果

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0 项与 KANAPH Therapeutics, Inc. 相关的专利（医药）

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3

项与 KANAPH Therapeutics, Inc. 相关的文献（医药）

2024-08-01·Ophthalmology and Therapy

Pre-Clinical Studies of a Novel Bispecific Fusion Protein Targeting C3b and VEGF in Neovascular and Nonexudative AMD Models

Article

作者: Kim, Donggeon ; Chang, Jihoon ; Lee, Byoung Chul ; Kim, Nahmju ; Chung, Philip E D ; Lee, Minkyeong ; Lee, Yeri

INTRODUCTIONKNP-301 is a bi-specific fragment crystallizable region (Fc) fusion protein, which inhibits both C3b and vascular endothelial growth factor (VEGF) simultaneously for patients with late-stage age-related macular degeneration (AMD). The present study evaluated in vitro potency, in vivo efficacy, intravitreal pharmacokinetics (IVT PK), and injectability of KNP-301.METHODSC3b and VEGF binding of KNP-301 were assessed by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA), and cellular bioassays. A laser-induced choroidal neovascularization (CNV) model and a sodium iodate-induced nonexudative AMD model were used to test the in vivo efficacy of mouse surrogate of KNP-301. Utilizing fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) scans, the reduction in disease lesions were analyzed in a CNV mouse model. In the nonexudative AMD mouse model, outer nuclear layer (ONL) was assessed by immunofluorescence staining. Lastly, intravitreal pharmacokinetic study was conducted with New Zealand white rabbits via IVT administration of KNP-301 and injectability of KNP-301 was examined by a viscosity test at high concentrations.RESULTSKNP-301 bound C3b selectively, which resulted in a blockade of the alternative pathway, not the classical pathway. KNP-301 also acted as a VEGF trap, impeding VEGF-mediate signaling. Our dual-blockade strategy was effective in both neovascular and nonexudative AMD models. Moreover, KNP-301 had an advantage of potentially less frequent dosing due to the long half-life in the intravitreal chamber. Our viscosity assessment confirmed that KNP-301 meets the criteria of the IVT injection.CONCLUSIONSUnlike current therapies, KNP-301 is expected to cover patients with late-stage AMD of both neovascular and nonexudative AMD, and its long-term PK profile at the intravitreal chamber would allow convenience in the dosing interval of patients.

2023-04-04·Cancer Research

Abstract 3234: OCT-598, a novel EP2/EP4 dual antagonist, promotes anti-tumor immune responses in syngeneic mouse tumor models in combination with standard-of-care chemo- and immunotherapies

作者: Kim, Chang Gon ; Kim, Young Seob ; Kim, Dong Kwon ; Han, Yu Jin ; Lee, Sungwoo ; Baek, Sujeong ; Lee, Youngrae ; Han, Heekyung ; Yun, Mi Ran ; Kim, Young Taek ; Yoon, Taeyoung ; Jo, Seongin ; Kim, Mi Hyun ; Byeon, Youngseon ; Lee, Ji Yun ; Hong, Min Hee ; Kwon, Soonsang ; Lim, Sang Kyun ; Kang, Seong-San ; Lee, Yeri ; Pyo, Kyoung-Ho ; Shin, Young Sook ; Na, Kwangmin ; Cho, Byoung Chul ; Kim, Jae Hwan ; Lim, Sun Min ; Synn, Chun-Bong ; Kim, Donggeon ; Lee, Jii Bum ; Yang, Seung Min

AbstractProstaglandin E2 (PGE2) is widely recognized as one of the major bioactive lipids that, with the striking regenerative potential, promote drug-resistance in cancer cells as well as immune evasion in the tumor microenvironment (TME). Primarily driven by apoptotic cell death, PGE2 is thought to elicit wound-healing responses to help provide an immunosuppressive and proliferative niche that supports cancer stem cell repopulation and thereby therapy-resistance. While COX1/2 inhibitors that attenuate PGE2 production have shown promising anti-cancer effects in various (pre-)clinical settings, the gastrointestinal- and cardiotoxicities precluded their development as anti-cancer agents. It is anticipated that specific targeting of PGE2 signaling via its cognate receptors constitutes a safer and potentially more effective approach. Of the receptor subtypes EP1-4, Gα,s-coupled EP2 and EP4 are believed to be directly involved in immunosuppressive effects of PGE2.OCT-598 is a novel, highly potent and selective EP2/EP4 dual antagonist with Ki values of 23 nM and 0.2 nM vs EP2 and EP4, respectively. PGE2 inhibited normal differentiation of human monocytes into CD1a+CD16- dendritic cells under the presence of GM-CSF and IL-4 and promoted differentiation towards CD1a-CD16+ macrophages in vitro. However, EP2/EP4 dual inhibition by OCT-598 reversed this phenomenon to a greater extent than either EP2- or EP4-specific inhibitor alone. In vivo, OCT-598 effected tumor growth inhibition in multiple syngeneic mouse models as a single agent as well as in combination with an immune checkpoint blocker (ICB). Furthermore, the addition of OCT-598 to the lung cancer standard-of-care regimen (anti-PD-1 plus chemotherapy) in TC-1 mouse lung adenocarcinoma model gave rise to complete tumor regression. In conclusion, dual blockade of EP2 and EP4 by OCT-598 is shown to be a compelling strategy to reinforce antitumor effects by thwarting PGE2-mediated therapy resistance and immune evasion.Findings from this study provide a rationale for clinical development of OCT-598 as a therapeutic option for human malignant cancers.Citation Format: Youngrae Lee, Sujeong Baek, Dong Kwon Kim, Yeri Lee, Donggeon Kim, Seongin Jo, Sang Kyun Lim, Young Sook Shin, Soonsang Kwon, Seung Min Yang, Young Taek Kim, Seong-San Kang, Chun-Bong Synn, Kwangmin Na, Mi Hyun Kim, Heekyung Han, Yu Jin Han, Sungwoo Lee, Jae Hwan Kim, Mi Ran Yun, Youngseon Byeon, Young Seob Kim, Ji Yun Lee, Jii Bum Lee, Chang Gon Kim, Min Hee Hong, Sun Min Lim, Kyoung-Ho Pyo, Byoung Chul Cho, Taeyoung Yoon. OCT-598, a novel EP2/EP4 dual antagonist, promotes anti-tumor immune responses in syngeneic mouse tumor models in combination with standard-of-care chemo- and immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3234.

2023-04-04·Cancer Research

Abstract 4016: Discovery of a small-molecule EGFR inhibitor that can potently target various EGFR mutants, including C797S mutant, in vitro and in vivo

作者: Jang, Anna ; Lee, Kiram ; Kim, Dongsu ; Kim, Miyeon ; Park, Dohyun ; Kim, Donggeon ; Yoon, Kyeong Jin ; Lee, Yeri ; Lim, Sang Kyun ; Jeon, Yeejin ; Choi, Sung Pil

AbstractEGFR is one of receptor tyrosine kinases (RTKs) and, upon ligand binding, turns on the downstream signals that include oncogenic RAS/MEK/ERK, PI3K/AKT/mTOR, and JAK/STAT pathways. EGFR gene mutations, such as Exon 19 deletion (Del19) and L858R mutations, induce abnormal activation of the EGFR protein even in the absence of the ligand leading to various cancers. EGFR mutations are found in non-small cell lung cancer (NSCLC) patients with 10-15% frequency (approximately 50% in Asian patients).Starting from Del19 and L8585R mutations, additional mutations in the EGFR gene occur during the treatment with 1st/2nd/3rd generation EGFR inhibitors, resulting in Del19/T790M, L858R/T790M, Del19/T790M/C797S, L858R/T790M/C797S, Del19/C797S, and L858R/C797S mutations. While double mutations that include the T790M mutation have been efficaciously treated with Osimertinib, there are currently no approved therapies that can effectively target the C797S-containing mutants.Here we present preclinical data showing a small-molecule inhibitor that effectively disables EGFR mutants, including Del19/T790M/C797S, L858R/T790M/C797S, Del19/C797S, and L858R/C797S mutants. High potency and selectivity were confirmed by in vitro kinase assays and cellular assays. Outstanding anti-cancer activity was observed in mouse xenograft models with various EGFR mutations and, importantly, it was inactive in the EGFR wild-type model. With confirmed brain penetrance through in vivo studies, our potent EGFR inhibitor may provide a great therapeutic potential for patients with EGFR mutation-driven NSCLC.Citation Format: Yeejin Jeon, Kiram Lee, Anna Jang, Miyeon Kim, Kyeong Jin Yoon, Yeri Lee, Dongsu Kim, Donggeon Kim, Dohyun Park, Sang Kyun Lim, Sung Pil Choi. Discovery of a small-molecule EGFR inhibitor that can potently target various EGFR mutants, including C797S mutant, in vitro and in vivo. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4016.

100 项与 KANAPH Therapeutics, Inc. 相关的药物交易

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100 项与 KANAPH Therapeutics, Inc. 相关的转化医学

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2024年11月22日管线快照

管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

药物发现

2

9

临床前

其他

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当前项目

药物(靶点)	适应症	全球最高研发状态

KNP 502 ( EP2 x EP4 )	实体瘤更多	临床前
KNP-101 ( IL-12 )	实体瘤更多	临床前
KNP-301 ( C3 x VEGF )	糖尿病性神经病变更多	临床前
SHP2抑制剂(kanaph Therapeutics) ( SHP2 )	肿瘤更多	临床前
KNP-701 ( EGFR x c-Met )	非小细胞肺癌更多	临床前