On December 9, 2019 Advaite Inc., a Chicago, IL based oncology-focused biotech company developing novel therapeutics and diagnostics to help patients suffering from debilitating diseases, has reported that it has entered into an exclusive license option agreement with the George Washington University with respect to the intellectual property of a novel AMES Negative HDAC6 inhibitor (Press release, Advaite, DEC 9, 2019, View Source [SID1234552171]). Histone Deacetylases modulate a multitude of cellular processes and are part of the regulation of cellular pathways involved in anti-tumor immunologic responses. Selective inhibition of HDAC6 slows tumor growth in various cancer models. Under terms of this agreement, Advaite has the option to exclusively license intellectual property covering methods of use and pharmaceutical compositions.

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"We look forward to future success by advancing the development of this novel HDAC6 inhibitor to treat a multitude of cancers, to ease suffering and extend life. This epigenetic regulator can have a potentially enormous therapeutic effect on patients who continue to suffer from debilitating cancer, as there is a great need for therapies that deliver an effective response, and specifically ones which are not limited by their toxicity profile. George Washington University’s expertise with HDACs provide a perfect relationship for Advaite to advance truly viable, state of the art, impactful technology," said Karthik Musunuri, CEO & Co-Founder of Advaite.

"The quest for newer and more effective ways of treating cancer has now led to an extensive focus on the involvement of the immune system and its capacity to recognize and engage tumor cells. Recent findings from several research groups have demonstrated that ultra-selective HDAC6 inhibitors have the unique capacity of remodeling of the cellular composition of tumors, favoring the recognition and killing of cancer cells by the immune system. Our novel HDAC6 inhibitor has shown to have reduced toxic effects, thus clearly differentiating from previous HDAC inhibitors used in the clinic," said Alejandro Villagra, Ph.D., Member of the Immunology and Microbial Oncology Research Program at the GW Cancer Center and Assistant Professor of Biochemistry and Molecular Medicine at the GW School of Medicine and Health Sciences.

On December 9, 2019 Australian life sciences company, QBiotics Group Limited (QBiotics) is reported the publication[1] of positive results from a first in-human Phase I clinical trial of its anticancer pharmaceutical, tigilanol tiglate (EBC-46) in EBioMedicine, a peer-reviewed translational biomedical research journal by The Lancet (Press release, QBiotics, DEC 9, 2019, View Source;efficacy-of-tigilanol-tiglate-in-solid-tumours-300971159.html [SID1234552170]).

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The key objectives of this Phase I, open-label, single-arm, non-randomised, dose-escalation study were to determine the safety profile, tolerability, pharmacokinetics (PK), and preliminary antitumour efficacy of tigilanol tiglate when administered once by intratumoural injection. Tigilanol tiglate was generally well tolerated and doses escalated from 0.06 to 3.60 mg/m[2], without reaching a maximum tolerated dose.

The study was conducted in 22 patients at four hospital sites in Australia[1]. Patients were recruited with a range of tumour types including squamous cell carcinoma, basal cell carcinoma, melanoma, breast adenocarcinoma, atypical fibroxanthoma, atypical myxoid fibrosarcoma, metastatic colorectal adenocarcinoma, adenoid cystic carcinoma and angiosarcoma. Signs of clinical activity were observed in all nine tumour types, even at the lowest doses.

"As this was a first-in-human, single dose safety study, the expectation of a strong anticancer response was low. However, the results revealed a 27% treatment response (in 6 patients), including an 18% complete response (in 4 patients) with full tumour destruction across a wide variety of solid tumour types.

"Solid tumours account for up to 80% of all tumour types,[3] so the results from this Phase I study indicate potentially broad applications for tigilanol tiglate in a range of tumours, and an important advancement for our pharmaceutical," said QBiotics Group CEO and Managing Director, Dr Victoria Gordon.

"Additionally, two patients with melanoma demonstrated an anenestic (or abscopal) response, where non-injected tumours at different locations in the body also reduced in size. These results were achieved despite many patients not receiving an optimal dose,[1]" added Dr Gordon.

The vast majority (96%) of adverse events (AEs) were mild to moderate, with the most commonly reported AE being injection site reaction related to the mode of action of tigilanol tiglate. AEs were generally managed with symptomatic therapy.[1]

"Given the very good safety profile, and positive antitumour responses observed, this study supports further development of tigilanol tiglate as a potential treatment of solid tumours," said Dr Gordon

"Results from this study also underpins selection of our initial lead indication and our recently announced Phase I/II trial of tigilanol tiglate in patients with Head and Neck Squamous Cell Carcinoma (HNSCC), in which the first patient was successfully dosed last week," Dr Gordon said.

The Phase I/II open label "QBC46-H03" study, is a dose escalation study in patients with HNSCC aimed at determining the maximum tolerated dose (MTD) and recommended dose level for further studies. The study will also investigate safety, tolerability and tumour response following single or multiple (two to three) doses of tigilanol tiglate. It will enrol up to 40 patients from the Tata Medical Centre in Kolkata, the Tata Memorial Hospital in Mumbai, and other clinical sites in Australia.

ISSUED BY

QBIOTICS GROUP LIMITED – www.QBiotics.com

FOR FURTHER
INFORMATION

DR VICTORIA GORDON, CEO & MANAGING DIRECTOR, QBIOTICS GROUP
[email protected] or + 61 418 453 737

On December 9, 2019 Nouscom, an immuno-oncology company developing off-the-shelf and personalized cancer neoantigen vaccines, reported that the first patient has been dosed in a Phase 1 clinical trial evaluating its lead candidate, NOUS-209 (Press release, NousCom, DEC 9, 2019, View Source;first-patient-dosed-in-a-phase-1-trial-with-nous-209-an-off-the-shelf-neoantigen-cancer-vaccine-in-msi-high-solid-tumors-300971098.html [SID1234552169]). In this first-in-human trial NOUS-209, an off-the-shelf therapeutic vaccine based on shared tumor neoantigens, is being administered to patients with Microsatellite Instable High (MSI-H) gastric, colorectal and gastro-esophageal junction cancers (tumors characterized by a defective DNA mismatch repair system) in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab.

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NOUS-209-01 (NCT04041310) is a US multicenter Phase 1 open-label, dose-escalation study, assessing the safety and tolerability of the NOUS-209 vaccine in combination with pembrolizumab to determine the recommended Phase 2 dose. The study will evaluate vaccine-induced immune responses, as well as preliminary signs of anti-tumor activity in enrolled patients. Based on preclinical data, NOUS-209 is expected to induce potent and broad CD8+ and CD4+ responses in humans. Initial clinical data are expected in 2020.

Dr. Michael J. Overman, Principal Investigator of the trial and Professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, explained: "We have seen tremendous change in our approach to MSI-high metastatic solid tumors over the last few years, but the majority of patients do not respond to single agent immunotherapy. Hence, further optimization of our approach for MSI-high cancers is needed. Agents like NOUS-209 that stimulate the patient’s immune response and direct it specifically against the cancer cells reflect a tremendous scientific evolution in our understanding of these cancers and represents an extremely promising approach for these cancers."

Dr. Elisa Scarselli, Chief Scientific Officer and Co-Founder of Nouscom, said "This first-in-human trial evaluating NOUS-209 in combination with pembrolizumab is a significant milestone for Nouscom. NOUS-209 leverages a core strength of the company’s platform, namely the capacity of its proprietary viral vectors to encode a large number of neoantigens. NOUS-209 was named because it comprises 209 shared Frame Shift Peptides (FSPs) selected using a proprietary algorithm. This feature of NOUS-209 enables it to be developed as an off-the-shelf neoantigen vaccine that does not require patient screening prior to treatment. Furthermore, it is designed to have broad coverage across the MSI patient population by targeting multiple neoantigens in each patient, and as such is expected to address tumor heterogeneity. We look forward to the initial clinical data in 2020."

On December 9, 2019 CARsgen Therapeutics, a clinical-stage biopharmaceutical company committed to discovering and developing a combined platform of Chimeric Antigen Receptor T (CAR-T) cell therapies and monoclonal antibodies for cancer, reported that one of its leading drug candidates, AB011 humanized claudin18.2 monoclonal antibody for the treatment of patients suffering from advanced gastric and pancreatic adenocarcinoma, has received Investigational New Drug (IND) clearance from the National Medical Products Administration (NMPA) in China (Press release, Carsgen Therapeutics, DEC 9, 2019, View Source [SID1234552168]).

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"We are excited to be moving AB011 into clinical development as a potentially best-in-class monoclonal antibody against claudin18.2, a rational target with outstanding properties for development of a monoclonal antibody product," said Dr. Zonghai Li, founder, CEO and CSO of CARsgen. "Currently, patients with advanced gastric and pancreatic cancer have a poor prognosis, and there’s a clear unmet medical need for better treatment options. We look forward to beginning the clinical investigation of AB011, which has shown promising results in preclinical models. We intend to submit an IND application for AB011 to the U.S. FDA in 2020."

AB011 is the first humanized monoclonal antibody targeting claudin18.2 entering clinical trials. Claudin18.2 is a stomach-specific isoform of claudin-18 (1-3). Histologically, it is only expressed in short-lived differentiated cells and not expressed in the stem cell zone of the stomach mucosa. Pathologically, it is highly expressed in a variety of cancer types, including gastric and pancreatic cancer. These characteristics suggest that claudin18.2 is a rational target for cancer.

References:

1. Jiang H, Shi Z, Wang P, Wang C, Yang L, Du G, et al. Claudin18.2 – specific chimeric antigen receptor engineered T cells for the treatment of gastric cancer. J Natl Cancer Inst 2019;111:409-18.

2. Osanai M, Takasawa A, Murata M, Sawada N. Claudins in cancer: bench to bedside. Pflugers Arch 2017;469:55–67.

3. Soini Y. Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology 2005; 46:551–60.

On December 9, 2019 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics to treat cancer, reported further progress on key elements of its ongoing Phase 1/2 clinical trial entitled "A Phase 1/2 Study in Patients with Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions" (ClinicalTrials.gov Identifier: NCT03947385) (Press release, Ideaya Biosciences, DEC 9, 2019, View Source [SID1234552167]). This clinical trial is evaluating the tolerability and preliminary clinical activity of IDE196 for the treatment of Metastatic Uveal Melanoma (MUM) and other solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations activating the PKC signaling pathway.

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"The pharmacokinetic clinical sub-study for the tablet formulation is on-track to start in January 2020. This may enable the initiation of the Phase 2 expansion to coincide with potential introduction of the tablet in Q1 2020. We also continue to evaluate the Phase 1 dose escalation data, including pharmacokinetic and tolerability data, as we target to advance IDE196 into the potentially registration-enabling study for MUM," said Julie Hambleton, M.D., Chief Medical Officer and Senior Vice President at IDEAYA Biosciences.

Key updates include:

Initiated 13-week GLP-compliant toxicology studies in 2 species in November 2019, in support of registration-enabling FDA requirement to submit study results prior to enrollment of more than approximately 50 patients in the investigational arm of the clinical trial that will support a marketing application
Pharmacokinetic Phase 1 clinical sub-study with immediate release tablet formulation of IDE196 scheduled to initiate in January 2020, in support of potential introduction of the tablet in the Phase 2 clinical trial in Q1 2020
Targeting initiation of Phase 2 single-arm potentially registration-enabling clinical trial in MUM in Q1 2020, which we anticipate may coincide with introduction of tablet formulation
Targeting initiation of combination clinical trial of IDE196 plus a MEK inhibitor in H1 2020, accelerated from earlier guidance. Preclinical evaluation of potential additional combinations ongoing
Total of 40 patients enrolled in the Phase 1 portion of the Phase 1/2 GNAQ/11 basket trial as of as of December 6, 2019, including 38 MUM patients, for which dose escalation is complete, and 2 non-MUM patients, for which enrollment is ongoing
Launching the IDEAYA Genomics Profiling Initiative (IDEAYA GPI). IDEAYA GPI is a company initiative leveraging various Next Generation Sequencing (NGS) platforms, including in partnership, to identify patients having tumors with specific mutations, such as tumors with activating GNAQ/11 mutations for potential enrollment in our IDE196 basket trial
On track to present interim clinical data from the GNAQ/11 Phase 1/2 monotherapy basket trial in Q2/Q3 2020
"We are excited for the opportunity to initiate the single-arm Phase 2 monotherapy expansion, which is potentially registration-enabling for MUM. We also look forward to advancing the clinical combination of IDE196 with MEK, as well as the GNAQ/11 basket trial to evaluate the clinical activity of IDE196 in non-MUM patients, including in skin melanoma," said Yujiro S. Hata, Chief Executive Officer and President at IDEAYA Biosciences.