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ESSA Pharma Presents New Data on EPI-7386 at the European Society of Medical Oncology (ESMO) 2019 Congress

On September 28, 2019 ESSA Pharma Inc. (Nasdaq: EPIX) (TSXV: EPI), a pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported new preclinical data on ESSA’s lead Investigational New Drug ("IND") candidate at the 2019 American Urological Association ("AUA") Annual Meeting (Press release, ESSA, SEP 28, 2019, View Source [SID1234539899]).

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In an oral poster presentation titled, "EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer", a deeper preclinical characterization of EPI-7386 was presented. The poster shows that, in preclinical studies, EPI-7386 demonstrates:

Activity in multiple in vitro full length androgen receptor (AR) and AR-V7 splice variant driven cellular models.
Robust antitumor activity as a single agent and in combination with enzalutamide in the VCaP xenograft prostate cancer model.
Antitumor activity in enzalutamide-resistant prostate cancer xenograft models, 22Rv1 and LNCaP95, with no antitumor activity, as expected, in a non-functional androgen receptor PC-3 prostate cancer xenograft model.
Wide therapeutic index as demonstrated by a broad dose response in the VCaP model.
High plasma exposures in animal studies using a new suspension formulation.
Abstract ID:

503P

Abstract Title:

EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for
the treatment of prostate cancer

Presenter:

Ronan Le Moigne, PhD

Date:

Saturday September 28, 2019

Time:

12:00pm CEST

Location:

Hall 4, Fira Gran Via, Barcelona, Spain

Zymeworks Announces Updated Single Agent Data for HER2-Targeted Bispecific Antibody ZW25 at European Society for Medical Oncology (ESMO) Congress

On September 28, 2019 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported updated data from the ongoing multi-center Phase 1 clinical trial evaluating ZW25 in patients with HER2‑expressing solid tumors, including biliary tract cancer (BTC), colorectal cancer (CRC), gynecological cancers, and gastroesophageal adenocarcinoma (GEA), in a poster discussion presentation at the ESMO (Free ESMO Whitepaper) 2019 Congress, taking place September 27 – October 1 in Barcelona, Spain (Press release, Zymeworks, SEP 28, 2019, View Source [SID1234539892]).

"The data presented today at ESMO (Free ESMO Whitepaper) confirm previous findings that ZW25 monotherapy can provide durable disease control in patients with a variety of HER2-expressing solid tumors that have progressed following standard of care therapies, including HER2-targeted agents," said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. "Notably, the single agent objective response rate in biliary tract cancer is highly encouraging given the poor prognosis and limited treatment options for these patients. We are working closely with regulatory agencies to initiate a registration-enabling Phase 2 trial in second-line HER2‑expressing biliary tract cancer with the goal of bringing ZW25 to patients as quickly as possible."

Based on the data from the ongoing Phase 1 study, Zymeworks has initiated a broad clinical development program for ZW25 in multiple HER2-expressing cancers. In addition to the Phase 2 BTC trial announced today, Zymeworks is continuing to evaluate ZW25 as a potential treatment for patients with other HER2-expressing cancers, including CRC and gynecological cancers (Phase 1; NCT02892123). For patients with HER2-expressing GEA, ZW25 is being developed as a first-line treatment in combination with standard of care chemotherapy (Phase 2; NCT03929666). Zymeworks also plans to initiate a Phase 2 study of ZW25 in combination with a CDK4/6 inhibitor and hormone therapy in third-line HER2-expressing, HR-positive breast cancer.

ZW25 Clinical Results Presented Today
The Safety, Efficacy and Biomarker Results of the HER2-Targeted Bispecific Antibody ZW25 in HER2-Expressing Solid Tumors (Abstract# 3575, Poster Discussion on Saturday, September 28 at 4:30 pm CEST)

Findings from this ongoing Phase 1 study of ZW25 in patients with HER2-expressing solid tumors were last presented at the 2018 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium. The updated results were presented today by Dr. Funda Meric-Bernstram, M.D., Clinical Investigator and Chair of the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.

Data were reported from 58 patients diagnosed with HER2-expressing solid tumors other than breast cancer who received ZW25 at the recommended dose of either 10 mg/kg weekly or 20 mg/kg every other week. Patients had a median age of 61 years and received a median of four prior therapies. Thirty-two (55%) patients received prior HER2‑targeted therapies including 87% of GEA patients. Of all patients, 23 were diagnosed with GEA, 13 with CRC, nine with BTC, and 13 with other HER2‑expressing cancers, including endometrial, ovarian, pancreatic, and salivary gland.

At the time of data cut-off, 46 of 58 patients were response evaluable. Overall, the majority of patients experienced a decrease in their target lesions with a disease control rate of 72%, comprising 16 (35%) patients with partial responses and 17 (37%) with stable disease. The objective response rate in the six evaluable biliary tract cancer patients was 67%, with the majority of patients experiencing disease control greater than six months. In the 11 CRC and 19 GEA patients, the objective response rates were 36% and 32%, respectively. The overall median progression-free survival was 5.2 months, with 27 (47%) of the 58 total patients still on study at the time of data cut-off.

Among all patients, ZW25 was well tolerated as an outpatient therapy. The most common adverse events were diarrhea, infusion-related reaction, and nausea. All treatment-related adverse events occurring in 10% or more of patients were Grade 1 or 2.

About the Phase 1 Clinical Trial

Zymeworks’ Phase 1 study has three parts. From part one of the study (the dose-escalation phase), the recommended single-agent dose was determined to be 20 mg/kg once every two weeks or 10 mg/kg weekly. In the second part of the study (the cohort expansion phase), additional patients are being enrolled to further assess ZW25’s single-agent tolerability and anti-tumor activity against a variety of cancer types in different settings. The third part of the study (the combination phase) is underway and evaluating ZW25 in combination with selected chemotherapy agents in gastroesophageal and breast cancer patients with HER2 high or lower HER2 expression levels.

About ZW25

ZW25 is being evaluated in Phase 1 and Phase 2 clinical trials across North America and South Korea. It is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging anti-tumor activity in patients. Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with any solid tumor that expresses HER2. The FDA has granted Fast Track designation to ZW25 for first-line gastroesophageal adenocarcinoma in combination with standard of care chemotherapy and Orphan Drug designation to ZW25 for the treatment of both gastric and ovarian cancers.

ESMO 2019: Forbius Demonstrates Target Engagement in Phase 1 Immuno-Oncology Clinical Trial with AVID200, First-in-Class TGF-beta 1 & 3 Inhibitor

On September 28, 2019 Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer, reported results from its non-clinical GLP toxicology program with first-in-class selective TGF-beta inhibitor AVID200 and evidence of TGF-beta target engagement in patients treated with this novel immuno-oncology agent at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Annual Congress in Barcelona (Press release, Forbius, SEP 28, 2019, View Source [SID1234539891]).

The presentation detailed for the first time that AVID200 administered at doses of ≥1 mg/kg sequestered its target TGF-beta in patient blood over the entire dosing period.

Key highlights of today’s presentation at ESMO (Free ESMO Whitepaper) (#504P):

AVID200 selectively neutralizes TGF-beta 1 & 3 with pM potency in vitro, and increases T-cell-mediated cytotoxicity as well as immune checkpoint inhibitor efficacy in syngeneic mouse tumor models
AVID200 was well tolerated in 1- and 6-month GLP toxicology studies in non-human primates
AVID200 in patient blood sequestered peripheral TGF-beta over the entire dosing period
A Phase 1a AVID200 monotherapy dose-escalation clinical trial is currently enrolling solid tumor patients (AVID200-03; NCT03834662)
About TGF-beta 1 & 3

TGF-beta 1 & 3 are the main oncogenic TGF-beta isoforms expressed by many solid tumors. They are believed to play a major role in T-cell suppression, fibrosis, and resistance to anti-PD-(L)1 therapies such as nivolumab (Opdivo) and pembrolizumab (Keytruda) (Chakravarthy et al., Nature Comm., 2018; Tauriello et al., Nature, 2018; Mariathasan et al., Nature, 2018).

About AVID200 and the AVID200-03 Trial (NCT03834662)

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 & 3 undergoing Phase 1 clinical testing in solid tumors and fibrotic diseases. TGF-beta 1 & 3 are the principal disease-driving isoforms, while TGF-beta 2 is responsible for normal cardiac function and hematopoiesis.

AVID200’s selectivity for TGF-beta 1 & 3 was designed to achieve optimal efficacy while circumventing cardiac and other safety issues that have limited the applicability of older-generation, non-selective TGF-beta inhibitors. Therefore, AVID200 is positioned to be an effective and well-tolerated therapeutic in a variety of clinical settings, including in combination with anti-PD-(L)1 therapy.

AVID200-03 (NCT03834662) is an open label, multicenter, dose-escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor effects of AVID200 in patients with advanced or metastatic solid tumor malignancies.

Bicycle Therapeutics Announces Presentation of Updated Data from Phase I/IIa Trial Evaluating BT1718 in Patients with Advanced Solid Tumors at ESMO 2019 Annual Congress

On September 28, 2019 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new class of therapeutics based on its proprietary bicyclic peptide (Bicycles) product platform, reported the presentation of updated data from a Phase I/IIa trial conducted in collaboration with Cancer Research UK and evaluating BT1718 in an unselected group of patients with advanced solid tumors (Press release, Bicycle Therapeutics, SEP 28, 2019, View Source [SID1234539890]). The results are being presented by Natalie Cook, Ph.D., a study investigator and Senior Clinical Lecturer at the University of Manchester, today from 12:00-13:00 CET in a poster session at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Annual Congress in Barcelona, Spain. The poster is available on the Publications section of bicycletherapeutics.com.

"The data being presented at ESMO (Free ESMO Whitepaper) demonstrate encouraging progress of the dose escalation portion of the Phase I/IIa trial evaluating BT1718," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "We believe these early data underscore the potential of Bicycles as a novel therapeutic modality and plan to provide additional updates from across our pipeline at medical meetings through the rest of this year."

Patients in the Phase I dose escalation were assessed for anti-tumor activity, safety and pharmacokinetics up to the data cutoff of August 7, 2019. Based on data from patients in cohorts across dose levels tested, many of which are below the predicted therapeutic range, 13 of 24 evaluable patients (54%) had stable disease at the eight-week timepoint, including a patient who experienced a 45% reduction in a target lesion. With once-weekly dosing, which is the expected schedule for the Phase IIa portion of the study, BT1718 has appeared tolerable, with manageable adverse events. The Phase I once-weekly dose escalation portion of the trial is ongoing, with dosing at levels equivalent to those associated with preclinical responses.

Across all dose levels and schedules tested, the most common treatment-related adverse events (>15%, n=28) were anemia, diarrhea, nausea, vomiting, fatigue, alanine aminotransferase increase, aspartate aminotransferase increase, blood alkaline phosphatase increase, gamma-glutamyltransferase increase, decreased appetite, lethargy and peripheral neuropathy.

Evaluation of pharmacokinetics demonstrated that BT1718 area under the curve (AUC) was approximately dose proportional over the range 0.6-25 mg/m2, and cycle 2 values were consistent with cycle 1. Mean (±SD) plasma clearance (CLp) was 33.6 (±24.5) L/h, with mean (±SD) volume of distribution (Vss) of 12.5 (±7.3) L, resulting in a terminal half-life (t1/2) of 0.2 to 0.5 hours. Two tumor biopsies were obtained from patients dosed at levels above 15 mg/m2 and analysis showed delivery of DM1 to the tumor consistent with preclinical models. These findings suggest rapid tumor penetration by BT1718. Further plasma and tumor DM1 analysis is ongoing to assess the extent of DM1 retention.

"We are on track to achieve the primary objectives of the Phase I portion of the study," said Udai Banerji, M.D., Ph.D, chief investigator of the study and Deputy Director of the Drug Development Unit at The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust. "BT1718 represents an exciting potential first-in-class drug, which appears tolerable in Phase I evaluation. Importantly, in two patient biopsies, we observed presence of cytotoxic payload to tumors consistent with targeted delivery and in a manner predicted by our preclinical models."

Nigel Blackburn, Ph.D., Cancer Research UK’s Director of Drug Development, said: "Based on our experience, these early clinical data are very promising and a testament to our strong partnership with Bicycle Therapeutics. We are pleased to help accelerate potentially groundbreaking new therapeutics such as BT1718 into clinical trials. This is an excellent example of the innovative work our Centre of Drug Development can support and is an important step toward helping more people survive cancer."

The Phase I/IIa study of BT1718 is being sponsored by Cancer Research UK. The primary objectives of the Phase I dose escalation portion of the trial are to select the recommended Phase II dose (RP2D) by establishing the maximum tolerated dose and maximum administered dose, and to assess the safety and toxicity profile of BT1718 in patients with advanced solid tumors. Following selection of the once-weekly RP2D, the Phase IIa portion of the study, consisting of up to four cohorts in selected indications in which MT1-MMP is expressed, will be initiated.

About BT1718

BT1718 is a Bicycle Toxin Conjugate being developed by Bicycle Therapeutics that targets Membrane Type 1 Matrix Metalloproteinase (MT1-MMP), also known as MMP-14, which has an established role in cell invasion and metastasis, is linked to poor outcomes and is over-expressed in many solid tumors. BT1718 has demonstrated promising target-dependent efficacy in preclinical models, including both cell- and patient-derived xenografts that are resistant to treatment with standards of care. In addition, it shows only a subset of the toxicities typically associated with other highly potent cancer treatments.

GRAIL to Present New Data in Late-Breaking Oral Presentation at the European Society for Medical Oncology (ESMO) 2019 Congress

On September 28, 2019 GRAIL, Inc., a healthcare company focused on the early detection of cancer, reported that new data supporting its technology to detect cancer at early stages with a single blood test will be presented as a late-breaking oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona, Spain (Press release, Grail, SEP 28 https, 2019, ://www.businesswire.com/news/home/20190927005539/en/GRAIL-Present-New-Data-Late-Breaking-Oral-Presentation [SID1234539889]).

"Most cancers go undetected until too late, and cancer remains the second leading cause of death worldwide. To address this challenge, we embarked on one of the most ambitious clinical study programs in genomic medicine in support of a novel multi-cancer approach to early cancer detection," said Anne-Renee Hartman, MD, Vice President of Clinical Development at GRAIL. "We are pleased to be presenting new data from our large-scale, rigorous clinical study program that demonstrate the ability of our test to detect more than 20 cancer types across all stages from a single blood draw, and identify where the cancer is located in the body, while minimizing the rate of false positives."

The data are being presented by Geoffrey R. Oxnard, MD, Dana-Farber Cancer Institute. The presentation slides will be available online at View Source at time of presentation.

GRAIL will also present additional new data from its ongoing studies evaluating its multi-cancer early detection test at ASCO (Free ASCO Whitepaper) Breakthrough taking place October 11-13, 2019 in Bangkok, Thailand.

ESMO Oral Presentation Details
Abstract LBA77
Geoffrey R. Oxnard, et al. Simultaneous multi-cancer detection and tissue of origin (TOO) localization using targeted bisulfite sequencing of plasma cell-free DNA (cfDNA)
Proffered Paper Session – Translational Research: September 28, 2019: 8:30-10:00 AM CEST, Pamplona Auditorium (Hall 2)

About GRAIL’s Investigational Multi-Cancer Early Detection Test

GRAIL is developing a next-generation sequencing (NGS) blood test for the early detection of multiple deadly cancer types. GRAIL’s high efficiency methylation technology preferentially targets the most informative regions of the genome and is designed to use its proprietary database and machine-learning algorithms to both detect the presence of cancer and identify the tumor’s tissue of origin. GRAIL’s sequencing database of cancer and non-cancer methylation signatures is believed to be the largest of its kind and covers approximately 30 million methylation sites across the genome. More than 20 cancer types across stages are represented within the database.

DNA methylation is a natural process used by cells to regulate gene expression. It is a chemical modification to DNA and a well-studied epigenomic feature of the genome. In cancer, abnormal methylation patterns and the resulting changes in gene expression can contribute to tumor growth. For example, hypermethylation can cause tumor-suppressor genes to be inactivated.