HP518 / Hinova Pharma - LARVOL DELTA

Phase 1 study of HP518, a PROTAC AR degrader in patients with mCRPC: results on safety, pharmacokinetics, and anti-tumor activity. (PubMed, Invest New Drugs) - P1 | "In this initial Phase 1 study, HP518 demonstrated an acceptable safety profile and responses in a limited subset of mCRPC patients with progression after ARPI warranting further investigation. ClinicalTrials.gov Identifier: NCT05252364."

Journal • P1 data • PK/PD data • Castration-Resistant Prostate Cancer • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation

A Phase I/II Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients (clinicaltrials.gov) - P1/2 | N=84 | Recruiting | Sponsor: Hinova Pharmaceuticals Inc. | Phase classification: P1 ➔ P1/2 | N=62 ➔ 84 | Trial primary completion date: Jul 2026 ➔ Oct 2025

Enrollment change • Phase classification • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

The first patient was enrolled in the Phase II clinical trial of HP518 tablets, an oral PROTAC drug developed by Hi-Tech Pharmaceuticals, for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in China [Google translation] (Sina Corp) - "Recently, Haichuang Pharmaceuticals...completed the first enrollment of subjects in the Phase II clinical trial of HP518 tablets, an oral PROTAC drug developed by the company for the treatment of metastatic castration-resistant prostate cancer (mCRPC). As of the date of publication, no oral PROTAC drugs with the same target have been approved for marketing at home and abroad."

Enrollment open • Castration-Resistant Prostate Cancer

Haichuang Pharmaceuticals: HP518 tablets intended for the treatment of androgen receptor (AR)-positive triple-negative breast cancer have been granted fast track designation by the U.S. FDA [Google translation] (Sina Corp) - "Haichuang Pharmaceutical...announced on the evening of June 30 that the company's research product HP518 tablets recently received 'Fast Track Designation' from the U.S. Food and Drug Administration ('FDA') for the treatment of androgen receptor (AR) positive triple-negative breast cancer. Currently, no similar target products have been approved for marketing at home and abroad."

Fast track • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Biomarker assessment and pharmacology of HP518, an AR PROTAC degrader from the phase 1 dose-escalation study in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2024) - P1 | "HP518, a novel AR PROTAC degrader, demonstrated encouraging efficacy in mCRPC pts, with responses seen in patients with full-length AR, AR LBD mutations, and AR amplification. These data support further investigation of HP518 in mCRPC pts."

Biomarker • Clinical • Metastases • P1 data • Tumor mutational burden • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • AR • CTCs • TMB

Haichuang Pharmaceuticals' new drug HP518 will release clinical data at the American Society of Clinical Oncology Annual Meeting [Google translation] (Sohu.com) - "Haichuang Pharmaceutical (688302) issued an announcement stating that the clinical research data of the company's independently developed PROTAC innovative drug HP518 will be released at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting...This study is the first human, non-randomized, open, multicenter Phase I dose-escalation study of HP518 in mCRPC patients, aiming to evaluate its safety, tolerability, pharmacokinetics and preliminary drug efficacy."

P1 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

HP518, an oral AR-targeting PROTAC for the treatment of AR positive triple negative breast cancer with a novel mechanism of action (AACR 2024) - "Nevertheless, AR inhibitors including enzalutamide and bicalutamide or the androgen biosynthesis inhibitor abiraterone have failed to demonstrate satisfying anti-tumor activity in clinical trials...HP518 in combination with alpelisib, a PI3Kα inhibitor shows a synergistic anti-tumor activity...Selected pre-clinical data will be presented. HP518 structure will not be disclosed."

Late-breaking abstract • Breast Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • AR • PIK3CA

A Phase I Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients (clinicaltrials.gov) - P1 | N=62 | Recruiting | Sponsor: Hinova Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Hinova Pharmaceuticals Aus Pty Ltd | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Preliminary data from a dose-escalation phase 1 study with HP518, an AR PROTAC degrader: Safety, tolerability, pharmacokinetics (PK), and first assessment of anti-tumor activity in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2024) - P1 | "HP518, a novel AR PROTAC degrader, demonstrates in this Phase 1a dose-escalation study, an acceptable safety/tolerability profile and a signal of efficacy in an unselected mCRPC patient population. The presence of AR LBD mutations may predict benefit from HP518, and merits further investigation in pts with mCRPC. Clinical trial information: NCT05252364."

Clinical • Metastases • P1 data • PK/PD data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A Phase I Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients (clinicaltrials.gov) - P1 | N=62 | Not yet recruiting | Sponsor: Hinova Pharmaceuticals Inc.

Metastases • New P1 trial • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Haichuang Pharmaceutical: Oral PROTAC drug HP518 tablets approved for clinical trials [Google translation] (Eastmoney.com) - "Haichuang Pharmaceutical...announced on the evening of November 1 that recently, the company received a drug clinical trial approval issued by the Drug Evaluation Center of the State Food and Drug Administration. Notification, agreeing to carry out clinical trials of HP518 tablets for the treatment of 'metastatic castration-resistant prostate cancer (mCRPC)'."

New trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Hinova Pharmaceuticals Aus Pty Ltd | Trial completion date: Mar 2025 ➔ Mar 2024

Metastases • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Hinova Pharmaceuticals Aus Pty Ltd | Recruiting ➔ Active, not recruiting | N=70 ➔ 22 | Trial primary completion date: Dec 2024 ➔ Mar 2024

Enrollment change • Enrollment closed • Metastases • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Haichuang Pharmaceutical: Application for Clinical Trial of PROTAC Drug HP518 Tablets Accepted [Google translation] (Daily Economic News - NBD) - "...On August 23, Haichuang Pharmaceuticals announced that the PROTAC drug HP518 tablets received a notice of acceptance for drug clinical trial applications."

New trial • Oncology

A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Hinova Pharmaceuticals Aus Pty Ltd | Trial completion date: Apr 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: Hinova Pharmaceuticals Aus Pty Ltd | Trial completion date: Apr 2025 ➔ Apr 2024 | Trial primary completion date: Dec 2024 ➔ Dec 2023

Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Hinova Receives FDA Proceed Authorization for its IND Application for HP518, an Orally Bioavailable Chimeric Degrader Targeting Androgen Receptor for Prostate Cancer Treatment (PRNewswire) - "Hinova Pharmaceuticals...recently announced that the U.S. Food and Drug Administration (FDA) has cleared the company's investigational new drug application (IND) for its innovative drug HP518, an oral chimeric degrader targeting androgen receptor (AR) for the treatment of metastatic castration-resistant prostate cancer (mCRPC). HP518 is currently in Phase I clinical trials in Australia. The open-label study approved by FDA will assess the safety, pharmacokinetics, and anti-tumor activity of HP518."

IND • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

After Australia, Haichuang Pharmaceutical’s PROTAC drug HP518 clinical application has been accepted by the US FDA [Google translation] (Stockstar) - "...Haichuang Pharmaceuticals announced that its investigational new drug application (IND) for its oral PROTAC drug HP518 targeting the androgen receptor (AR) has been accepted by the US FDA....This new drug clinical study accepted by the FDA is an open-label study designed to evaluate the safety, pharmacokinetics and anti-tumor activity of HP518 in patients with metastatic castration-resistant prostate cancer (mCRPC)."

IND • Genito-urinary Cancer • Oncology • Prostate Cancer

A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: Hinova Pharmaceuticals Aus Pty Ltd | N=45 ➔ 65 | Trial completion date: Apr 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Hinova Disclosed the Preclinical Results of HP518 (Oral AR PROTAC) at the 5th Annual TPD Summit (PRNewswire) - "Hinova Pharmaceuticals Inc...presented their preclinical results of HP518, an orally bioavailable chimeric degrader targeting androgen receptor (AR) for prostate cancer treatment, at the 5th Annual TPD Summit....Discovered and developed by Hinova, HP518 showed high degradation activity against fl-AR and most enzalutamide resistant AR point mutants, and demonstrated excellent antiproliferation activities against prostate cancer cell lines. Meanwhile, HP518 exhibited good metabolic stability and is stable in human plasma. HP518 showed excellent antitumor efficacy in xenograft model by oral dosing. HP518 was also well tolerated in preclinical tox studies."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=45 | Recruiting | Sponsor: Hinova Pharmaceuticals Aus Pty Ltd | N=30 ➔ 45

Enrollment change • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Hinova Pharmaceuticals Aus Pty Ltd

New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Hinova Announces First Patient Dosed in a Phase I Clinical Trial of HP518, an Orally Bioavailable Chimeric Degrader Targeting Androgen Receptor for Prostate Cancer Treatment (PRNewswire) - "Hinova Pharmaceuticals...announced that the first patient with metastatic castration-resistant prostate cancer (mCRPC) has been successfully dosed in a Phase I clinical trial of HP518, a highly selective and orally bioavailable chimeric degrader targeting androgen receptor (AR). The ongoing open-label Phase I study in Australia will evaluate the safety, pharmacokinetics, and anti-tumor activity of HP518 in patients with mCRPC."

Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer