Top 5 Target	Count

FGFR2 x FGFR3 x FGFR4	1
KRAS(GTPase KRas)	1
RET(Tyrosine-protein kinase receptor RET)	1
FGFR2(Fibroblast growth factor receptor 2)	1
CDK7(Cyclin-dependent kinase 7)	1

Drugs associated with Applied Pharmaceutical Science, Inc.

APS03118

Target

RET

Mechanism

RET inhibitors

Active Org.

Applied Pharmaceutical Science, Inc.

Originator Org.

Applied Pharmaceutical Science, Inc.

Active Indication

Advanced Malignant Solid Neoplasm [+5]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date-

APS-RNA-001

Target-

Mechanism-

Active Org.

Applied Pharmaceutical Science, Inc.

Originator Org.

Applied Pharmaceutical Science, Inc.

Active Indication

Solid tumor

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date-

APS009

Target-

Mechanism-

Active Org.

Applied Pharmaceutical Science, Inc.

Originator Org.

Applied Pharmaceutical Science, Inc.

Active Indication

Solid tumor

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date-

Clinical Trials associated with Applied Pharmaceutical Science, Inc.

NCT05653869 / RecruitingPhase 1

A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of APS03118 in Adult Patients With Unresectable Locally Advanced or Metastatic Solid Tumors Harboring RET Mutations or Fusions

This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antineoplastic activity of APS03118 administered orally in participants with RET-altered solid tumors.

Start Date06 Feb 2023

Sponsor / Collaborator

Applied Pharmaceutical Science, Inc.

CTR20222441 / RecruitingPhase 1

一项在携带RET突变或融合的不可切除、局部晚期或转移性实体瘤成人患者中研究APS03118的安全性、耐受性、药代动力学和初步疗效的I期研究

[Translation] A Phase I study investigating the safety, tolerability, pharmacokinetics, and preliminary efficacy of APS03118 in adult patients with unresectable, locally advanced, or metastatic solid tumors harboring RET mutations or fusions

主要目的：确定APS03118的最大耐受剂量（MTD）和/或II期推荐剂量（RP2D）评价APS03118的安全性和耐受性次要目的：评价APS03118的药代动力学（PK）特征根据第1.1版实体瘤疗效评价标准（RECIST）评估APS03118的初步抗肿瘤疗效

[Translation]

Primary objectives: Determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of APS03118 Evaluate the safety and tolerability of APS03118 Secondary objectives: Evaluate the pharmacokinetic (PK) characteristics of APS03118 Assess the preliminary anti-tumor efficacy of APS03118 according to RECIST version 1.1

Start Date17 Nov 2022

Sponsor / Collaborator

Applied Pharmaceutical Science, Inc.

100 Clinical Results associated with Applied Pharmaceutical Science, Inc.

0 Patents (Medical) associated with Applied Pharmaceutical Science, Inc.

Literatures (Medical) associated with Applied Pharmaceutical Science, Inc.

05 Apr 2024·Cancer Research

Abstract CT056: Development of a novel next-generation RET inhibitor

Author: Wang, Xiupeng ; Yang, Jing ; Chen, Minchun ; Wang, Yuxun ; Wang, Zongbao ; Liu, Yongbo ; Gao, Qin ; Chen, Qian ; Zhong, Jun ; Chen, Xiaohu ; Xie, Wenya ; Wang, Hao ; Ji, Yizhe ; Xiao, Ruxue

AbstractOncogenic RET alterations confer constitutive activation in multiple types of human cancers. Two first-generation selective RET inhibitors selpercatinib and pralsetinib have been approved for patients with RET-driven solid tumors including non-small cell lung cancer (NSCLC) and thyroid cancer. However, critical unmet medical needs remain due to drug resistance caused by RET mutations in patients treated with the first-generation RET inhibitors. To address this emerging clinical issue, we discovered a highly potent and selective RET inhibitor with novel chemical scaffold through structure-based drug design, APS03118. Preclinical studies showed APS03118 had stronger in vitro and in vivo biological activity than the first-generation RET inhibitors targeting a broad range of RET fusions and mutations. Importantly, APS03118 was highly potent against a series of resistant RET mutations including the solvent front mutations RET G810C/R/S (IC50 0.04-5.72 nM) and gatekeeper mutations RET V804E/L/M (IC50 0.04-1.36 nM). Off-target screen analysis using the 468-kinase panel demonstrated APS03118 was highly selective for RET. APS03118 was orally bioavailable with good ADME and PK properties and markedly suppressed tumor growth in various RET-driven mouse xenograft tumor models (tumor growth inhibition 87-108% at 10-30 mg/kg BID). In addition, APS03118 exhibited excellent brain penetrating properties with strong efficacy in the in vivo orthotopic brain tumor model. GLP toxicity studies showed acceptable safety profiles. APS03118 received IND approval from both US FDA and China NMPA, and was granted the fast-track designation by FDA. We recently achieved First-in-Human milestone for APS03118 and the Ph 1 clinical trial is ongoing. As of January 5, 2024, three dose levels have been tested. Plasma exposure of APS03118 increased proportionally following single and repeated administration of APS03118 at different doses. APS03118 was well tolerated in NSCLC and thyroid cancer patients harboring RET fusions or mutations relapsed on the chemotherapy, multi-kinase inhibitor and first-generation RET inhibitor therapy. In addition to the favorable safety profiles, we observed sign of efficacy in the RET altered cancer patients in response to APS03118 treatment even in the early clinical trial testing. Partial response and stable disease were observed in patients 2-4 months after administration of APS03118 and dose limiting toxicity (DLT) dose has not been reached. Dose escalation for APS03118 is continuing. Taken together, APS03118 is a novel highly potent and selective next-generation RET inhibitor overcoming resistance following treatment with the first-generation RET inhibitors. APS03118 warrants further clinical development.Citation Format: Jun Zhong, Ruxue Xiao, Wenya Xie, Minchun Chen, Xiaohu Chen, Hao Wang, Yongbo Liu, Qin Gao, Xiupeng Wang, Zongbao Wang, Qian Chen, Jing Yang, Yizhe Ji, Yuxun Wang. Development of a novel next-generation RET inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT056.

15 Jun 2022·Cancer Research

Abstract 5363: The preclinical selectivity and activity of APS03118, a highly selective and potent next-generation RET inhibitor

Author: Wang, Hao ; Liu, Yongbo ; Chen, Minchun ; Drilon, Alexander ; Subbiah, Vivek ; Lu, Shun ; Chen, Xiaohu ; Zhu, John ; Zhong, Jun ; Lu, Ying

AbstractBackgroud: Oncogenic RET is an actionable target across a variety of cancers. Selective RET inhibitors selpercatinib and pralsetinib were recently approved by the FDA and EMA for patients with RET-dependent NSCLC and thyroid cancers. The solvent front mutations (SFMs) RET G810C/S/R have been identified as mechanisms of acquired resistance to both drugs. The gatekeeper RET V804 mutation cannot be inhibited by selected next-generation RET inhibitors in development. APS03118 is a novel next-generation RET inhibitor which is potent against a range of RET fusions and mutations including both SFMs and gatekeeper mutations.Methods: The selectivity, anti-RET activity, and intracranial efficacy of APS03118 were confirmed in vitro and in vivo in a variety of RET-dependent tumor models.Results: APS03118 was highly selective against a panel of 468 kinases and demonstrated 130-fold selectivity over VEGFR-2. In enzymatic assays, APS03118 showed low nanomolar potency against wild type RET and 25 RET mutations/fusions, including the inhibition of RET G810R/C/S (IC50 0.04-5 nM) and RET V804M/L/E (IC50 0.04-1 nM). APS03118 inhibited RET phosphorylation (IC50 <15 nM) in Ba/F3 engineered RET cells (WT, G810R, V804M, M918T). In cell proliferation assays, APS03118 potently inhibited KIF5B-RET Ba/F3 (WT, V804M, V804L, M918T), CCDC6-RET Ba/F3 (WT, V804M, S904F), LC2/ad (CCDC6-RET), TT (RET C634W) (IC50 < 10nM); Ba/F3 RET G810R and G810S IC50 (8-65 nM). APS03118 demonstrated marked anti-tumor efficacy in vivo in RET-driven cell-derived (Ba/F3 KIF5B-RET, V804M, TT (C634W)) and patient-derived (KIF5B-RET, CCDC6-RET, CCDC6-RET V804M) xenograft tumor models. At 10 mg/kg BID, tumor regression was observed in these xenograft models (TGI 87-108%). Tumors completely subsided in CCDC6-RET orthotopic brain model with a 100% survival rate. In the Ba/F3 KIF5B-RET G810R xenograft model, APS03118 30 mg/kg BID showed 90% TGI and was well tolerated, and RET G810 mutations often drive clinical progression on current RET inhibitors.Conclusions: APS03118 is a novel highly selective next-generation RET inhibitor that possesses potent in vitro and in vivo activity against a diverse range of RET alterations, including SFMs-mediated resistance. A first-in-human phase 1 trial for patients with RET-driven solid tumors with activating RET alterations is planned for 2022.Citation Format: Alexander Drilon, Jun Zhong, Ying Lu, Yongbo Liu, Hao Wang, Minchun Chen, Xiaohu Chen, John Zhu, Shun Lu, Vivek Subbiah. The preclinical selectivity and activity of APS03118, a highly selective and potent next-generation RET inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5363.

01 Jun 2022·Journal of Clinical Oncology

The development of APS03118, a potent next-generation RET inhibitor for treating RET-inhibitor-resistant patients.

Author: Lu, Ying ; Zhu, John ; Wang, Hao ; Drilon, Alexander E. ; Lu, Shun ; Liu, Yongbo ; Subbiah, Vivek ; Chen, Xiaohu ; Zhong, Jun ; Chen, Minchun

e15107 Background: Oncogenic RET is an actionable target across a variety of cancers. Selective RET inhibitors selpercatinib and pralsetinib were recently approved by the FDA and EMA for patients with RET-dependent NSCLC and thyroid cancers. The solvent front mutations (SFMs) RET G810C/S/R have been identified as mechanisms of acquired resistance to both drugs. APS03118 is a novel next-generation RET inhibitor which is potent against a range of RET fusions and mutations including both SFMs and gatekeeper mutations. Methods: The selectivity, anti-RET activity, and intracranial efficacy of APS03118 were confirmed in vitro and in vivo in a variety of RET-dependent tumor models. Results: APS03118 was highly selective against a panel of 468 kinases and demonstrated 130-fold selectivity over VEGFR-2. In enzymatic assays, APS03118 showed low nanomolar potency against wild type RET and 25 RET mutations/fusions, including the inhibition of RET G810R/C/S (IC50 0.04-5 nM) and RET V804M/L/E (IC50 0.04-1 nM). APS03118 inhibited RET phosphorylation (IC50 < 15 nM) in Ba/F3 engineered RET cells (WT, G810R, V804M, M918T). In cell proliferation assays, APS03118 potently inhibited the proliferation of KIF5B-RET Ba/F3 (WT, V804M, V804L, M918T), CCDC6-RET Ba/F3 (WT, V804M, S904F), LC2/ad (CCDC6-RET), TT (RET C634W) (IC50 < 10nM); Ba/F3 RET G810R and G810S IC50 (8-65 nM). APS03118 demonstrated marked anti-tumor efficacy in vivo in RET-driven cell-derived (Ba/F3 KIF5B-RET, V804M, TT (C634W)) and patient-derived (KIF5B-RET, CCDC6-RET, CCDC6-RET V804M) xenograft tumor models at 10 mg/kg (TGI 87-108%). Tumors completely subsided in CCDC6-RET orthotopic brain model with a 100% survival rate. In the Ba/F3 KIF5B-RET G810R xenograft model, APS03118 30 mg/kg showed 90% TGI and was well tolerated, and RET G810 mutations often drive clinical progression on current RET inhibitors. The pharmacokinetic/pharmacodynamic relationship of APS03118 in Ba/F3 KIF5B-RET G810R and WT xenograft tumor model was investigated, and the sustained decrease of the phosphorylated RET were observed at 30 mg/kg with the plasma exposure exceed cell IC90. Conclusions: APS03118 is a novel highly selective next-generation RET inhibitor that possesses potent in vitro and in vivo activity against a diverse range of RET alterations, including SFMs-mediated resistance. APS03118 has received IND approval and Fast Track Designation from FDA, and a first-in-human phase 1 trial for patients with RET-driven solid tumors with activating RET alterations is planned for 2022.

100 Deals associated with Applied Pharmaceutical Science, Inc.

100 Translational Medicine associated with Applied Pharmaceutical Science, Inc.

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Pipeline Snapshot as of 29 Nov 2024

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

Discovery

Preclinical

Phase 1 Clinical

Current Projects

Drug(Targets)	Indications	Global Highest Phase

APS03118 ( RET )	Breast Cancer More	Phase 1
APS-RNA-001	Solid tumor More	Preclinical
APS009	Solid tumor More	Preclinical
Selective FGFR2 inhibitor(Applied Pharmaceutical Science) ( FGFR2 )	Solid tumor More	Discovery
FGFR2/3/4 inhibitor(Applied Pharmaceutical Science) ( FGFR2 x FGFR3 x FGFR4 )	Solid tumor More	Discovery

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