On December 9, 2020 TVAX Biomedical (TVAX), is a cancer immunotherapy company reported that is moving into its pivotal glioblastoma study for FDA regulatory approval (Press release, TVAX Biomedical, DEC 9, 2020, View Source [SID1234572552]). TVAX Immunotherapy could fundamentally change the way cancer is treated as T cells can kill all cancer cells, including cancer stem cells, without the toxicity of current treatments. With early promising outcomes, TVAX received Fast Track Designation and Orphan Product Designation from the FDA.

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Glioblastoma is an incurable brain cancer affecting >12,000 people annually in the US. This form of brain cancer killed Beau Biden, the son of President-elect Biden, and Senators John McCain and Ted Kennedy and countless others. TVAX is working to change that.

TVAX Immunotherapy is a cutting-edge approach to cellular therapy. The individualized therapy first helps the patient develop immunity against their cancer and the unique "neoantigens" that cancer cells produce. Next, T cells are removed from patient’s blood and activated in TVAX’s specialized manufacturing facility. Patients are then treated with billions of their own "killer" T cells that attack their cancer. Dr. Wayne Carter, TVAX Biomedical’s CEO, explains it like this, "TVAX’s technology uses ‘killer’ T cells that function like billions of smart bombs hunting and destroying cancer cells throughout the body. TVAX Immunotherapy has very few side effects because ‘killer’ T cells kill cancer cells, not normal cells."

This therapy has shown promising results for four-legged friends too. The ability to treat multiple types of cancer prompted TVAX to spin-off its animal health division into Elias Animal Health, an affiliate pursuing similar treatments in dogs. Elias is using the technology to treat osteosarcoma, an incurable bone cancer and is currently enrolling dogs for their registration study with the USDA.

TVAX Immunotherapy has been administered to more than 120 patients and has demonstrated efficacy against several cancers, producing numerous long-lasting complete and partial responses with none of the "off-target" short and long-term toxicity seen with CAR-T cell therapy, checkpoint inhibitors, and chemotherapies.

TVAX worked closely with the FDA to plan its critical glioblastoma registration study. Fast Track Designation affords many advantages, including a pathway to accelerated marketing approval. TVAX Immunotherapy has dramatically lower manufacturing costs compared to other cellular immunotherapies such as CAR-T therapies and manufacturing can be easily automated to facilitate large-scale commercialization.

On December 9, 2020 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported to share top-line final data from its phase I study of Cantrixil (TRX-E-002-1) in patients with persistent or recurrent ovarian cancer (NCT02903771) (Press release, Kazia Therapeutics, DEC 9, 2020, View Source [SID1234572551]).

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Key Points

25 patients with advanced metastatic ovarian cancer received at least one dose of Cantrixil at six sites in the United States and Australia, comprising 11 patients in Part A (dose escalation) and 14 patients in Part B (dose expansion)
Trial achieved its primary objective, determining the maximum tolerated dose (MTD) of Cantrixil to be 5 mg/kg
Overall, 16 patients were evaluable for efficacy. One patient demonstrated a complete response (CR) and two patients experienced a partial response (PR), according to industry-standard RECIST criteria, making an overall response rate (ORR) of 19%
The patient who experienced a complete response remains in remission some three years after her last dose of Cantrixil
The drug was generally well-tolerated, with primarily gastrointestinal toxicities observed (abdominal pain, vomiting, and nausea)
Australian lead investigator, Associate Professor Jim Coward, commented, "this was a heavily pre-treated population, comprising patients with very advanced disease. Existing treatment options for such patients are limited, and there remains an urgent need for new therapies. My colleagues and I are excited by the potential for Cantrixil to provide benefit here, and we look forward to seeing the drug move forward in its development."

Kazia expects the full data to be presented at a suitable academic conference and published in a peer-reviewed journal in 1H CY2021. In accordance with common practice, the full data will remain embargoed until they are formally published, in order not to prejudice the appropriate dissemination of the data, and only top-line data are discussed here.

Kazia CEO, Dr James Garner, commented, "we are very pleased to see the Cantrixil phase I study completed. The data unambiguously demonstrates the potential for Cantrixil to provide benefit in this very challenging patient population. With this positive data in hand, our focus now shifts to partnering activity, and we hope to transition Cantrixil to a company which both shares our belief in its potential and is able to apply the necessary resources and expertise to realise that potential over the next chapter of its development."

Background

The phase I study of Cantrixil in ovarian cancer (NCT02903771) commenced recruitment in December 2016. It was designed in two parts. Part A (dose escalation component) was intended to determine the maximum tolerated dose (MTD) of Cantrixil in women with ovarian cancer. Part B (dose expansion cohort) was intended to seek preliminary evidence of clinical efficacy, as well as providing a deeper understanding of pharmacokinetics and safety of Cantrixil. All patients received two cycles of treatment with Cantrixil monotherapy, followed by up to six cycles in combination with other chemotherapy agents.

Kazia announced completion of Part A in October 2018. At that stage, the study declared 5 mg/kg to be the MTD, and this dose was used for all patients in Part B. The main dose-limiting toxicity (DLT) was abdominal pain. 11 patients received at least one dose of Cantrixil in Part A.

Part B recruited an additional 14 patients, all of whom were treated at the MTD, with the goal of seeking exploratory signals of potential clinical efficacy. All 14 patients received at least one dose of Cantrixil in Part B. In total, 17 patients across Part A and Part B received Cantrixil at the MTD of 5 mg/kg.

The study completed recruitment in August 2019, and last patient last visit occurred in March 2020. Preliminary efficacy data was presented in September 2019 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting in Barcelona, Spain, and at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting in June 2020.

On December 9, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported updates on the clinical development of the company’s novel Bcl-2 inhibitor APG-2575, further demonstrating the drug candidate’s therapeutic potential (Press release, Ascentage Pharma, DEC 9, 2020, View Source [SID1234572550]).

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APG-2575 is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. As a bona fide Bcl-2 inhibitor, APG-2575 demonstrated desired target engagement. APG-2575 selectively binds to Bcl-2, disrupts Bcl-2:BIM complexes, and releases the proapoptotic protein BIM. Freed BIM subsequently activates BAX/BAK for pore formation on the mitochondria membrane, leading to mitochondrial outer-membrane permeabilization (MOMP), cytochrome c release, caspase activation, and apoptosis of cancer cells. APG-2575 is the first China-developed Bcl-2 inhibitor having entered clinical development in China. As a single agent, APG-2575 has potent antitumor activity in Bcl-2-dependent tumor cells, and has shown a broad range of antitumor activities when combined with other oncologic drugs. Previously, APG-2575 had received clearances and approvals for multiple Phase Ib/II clinical studies in China, Australia, and the US, and is currently being developed in a range of hematologic malignancies globally.

Highlights of the update

In total, 9 clinical studies are ongoing globally, with over 100 patients who have been administered APG-2575 at doses ranging from 20 mg to 1200 mg for the treatment of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), acute myeloid leukemia (AML), and high leukocyte acute leukemia (HCL), etc.
Studies of APG-2575 in the treatment of relapsed/refractory CLL (r/r CLL) have enrolled over 30 patients. Preliminary results show that an objective response rate (ORR) of 70% has been reached in evaluable patients.
On safety:
Maximum tolerated dose (MTD) has not been reached, and no dose-limiting toxicity (DLT) was observed.
No clinical or laboratory tumor lysis syndrome (TLS) was observed.
Most treatment-related adverse events (TRAEs) were of Grade 1 or 2.
Limited cases of neutropenia and thrombocytopenia.
APG-2575 has been granted three Orphan Drug Designations (ODDs) by the US FDA, for the treatment of CLL, MM, and Waldenström macroglobulinemia (WM).
"APG-2575 is a key drug candidate of Ascentage Pharma’s apoptosis-targeted pipeline," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the first China-developed Bcl-2 inhibitor having entered clinical development in China, APG-2575 as a single agent or in combinations has demonstrated great therapeutic potential and clinical advantages. We are accelerating the global clinical development of this drug candidate, which we hope will soon translate into a new therapeutic option for patients in China and around the world."

On December 9, 2020 Kintor Pharmaceutical Limited (HKEx: 9939) reported that the Group has collected positive data in phase II clinical trials of combination therapy of ALK-1 (GT90001) antibody and PD-1 (Nivolumab or Opdivo) antibody for the second line therapy of advanced hepatocellular carcinoma ("HCC") in Taiwan (the "Phase II Clinical Trial") (Press release, Suzhou Kintor Pharmaceuticals, DEC 9, 2020, View Source [SID1234572549]). The preliminary data of the ongoing Phase II Clinical Trial showed positive efficacy and safety results. The data collected in the Phase II Clinical Trial will be released at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) to be held between January 15-17, 2021.

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Poster presentation
Abstract Title:
Safety and efficacy of combination of GT90001, an anti-activin receptor-like kinase-1 (ALK-1) antibody, and nivolumab in patients with metastatic hepatocellular carcinoma (HCC)
Abstract Number: 326
First Author: Chiun Hsu, MD

GT90001 is a fully humanised monoclonal antibody that inhibits ALK-1/TGF-β signal transduction and tumor angiogenesis and a potential first-in-class antibody for which we obtained an exclusive global license from Pfizer, Inc. in February 2018. The Phase II Clinical Trial was commenced on May 7, 2019 in Taiwan to evaluate the safety and efficacy of GT90001 in combination therapy with Nivolumab in patients with advanced HCC who were progressed on or intolerant to first line therapy with Sorafenib or Lenvatinib.

The Phase II Clinical Trial (NCT03893695) was a single-arm, open-ended and two-stage clinical trial. The Phase II Clinical Trial mainly observed the safety, tolerability and anti-tumor activity of the combination therapy of GT90001 and Nivolumab. In the first stage (safety evaluation cohort), six patients were enrolled in the dose group of 7mg/kg of GT90001 biweekly and 3mg/kg of Nivolumab biweekly. In the second stage (expanded cohort), 14 patients were enrolled at the same dose for combination therapy. According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, patients received treatment until experiencing disease progression or intolerable toxicity was developed. The primary efficacy endpoint was the objective response rate (ORR) assessed by the investigators.

From July 9, 2019 to September 30, 2020, among the 20 evaluable patients, eight patients (40.0%) were observed partial remission (PR). The side effects were well tolerated and manageable. The pharmacokinetic parameters of GT90001 and Nivolumab are similar to those of monotherapy.

Dr. Tong Youzhi, the founder, Chairman and CEO of Kintor Pharmaceutical, said, "Upon obtaining the exclusive global rights of GT90001, Kintor has implemented the development strategy to combine GT90001 with immunotherapy. GT90001, in combination with Nivolumab, has showed positive efficacy and safety results. We are actively initiating MRCT phase II/III clinical trials in China and US for the treatment of advanced HCC. Meanwhile, we are exploring innovative therapies for the treatment of other solid tumors."

About GT90001

GT90001 is a fully human monoclonal antibody against ALK-1 (Activin Receptor-Like Kinase-1, Activin Receptor-Like Kinase-1). Kintor Pharmaceutical obtained the global exclusive development, production and commercialization rights from Pfizer in 2018. ALK-1 antibody can inhibit tumor blood vessel growth, reduce blood flow and angiogenesis by blocking the ALK-1 receptor pathway, thereby slowing tumor growth and changing the tumor microenvironment. As a potential first-in-class innovative drug in the world, it is expected to be used in the treatment of various solid tumors.Pfizer has conducted two phase I clinical trials on GT90001 in the United States, Italy, South Korea and Japan, which showed good safety and preliminary effectiveness in more than 100 patients with advanced solid tumors. Currently, Kintor Pharmaceutical is conducting phase II clinical trial of GT90001 combined with Nivolumab (PD-1 antibody) for the treatment of advanced liver cancer in Taiwan.

On December 9, 2020 Oblato, Inc. (the Company), a wholly owned U.S. subsidiary of the Korean biotech company GtreeBNT Co., Ltd., reported it had official discussions with the FDA on a detailed plan for a phase 1/2 clinical trial to start developing a new treatment for Diffuse Intrinsic Pontine Glioma (DIPG), a rare pediatric disease, using its proprietary drug, OKN-007 (Press release, Oblato, DEC 9, 2020, View Source [SID1234572548]).

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Through this FDA meeting, the Company obtained consent from the FDA on important matters, such as patient population, starting dose, approach for dose escalation, and criteria for evaluating disease response. Importantly, there was in depth discussion on how to actively utilize existing historical patient data instead of requiring a comparative group in consideration of the nature of DIPG, a severe rare pediatric glioma and the need for all patients to receive anti-cancer treatment. The FDA also gave detailed advice on pharmacokinetic assessment and standard of care radiation therapy during the clinical study. The detailed response from the FDA indicates their support and expectations for Oblato which is developing a new drug for the treatment of DIPG.

In particular, the FDA has been supportive of biopharmaceutical companies developing treatments for rare pediatric diseases. Furthermore, new drugs for rare pediatric diseases have been approved by the FDA if the efficacy was fully demonstrated even with a small clinical trial. In 2019, Vyondys 53 (golodirsen), a treatment for DMD (Duchenne muscular dystrophy) developed by Sarepta Therapeutics, was approved after just a single phase 1/2 clinical trial. Another example is Brineura (ceriponase alpha) that was developed by Biomarin and approved in 2017 for the treatment of CLN2/Batten disease after a single phase 1/2 clinical study.

"DIPG’s nonclinical studies using OKN-007 have been recognized as supportive to the proposed phase 1/2 trial plan for DIPG and were also fully accepted by the FDA during the meeting. If our treatment shows efficacy in the clinical study for DIPG, we will be able to apply for an NDA after the trial is completed," stated an official from the Company.

The FDA has already granted Oblato the Rare Pediatric Disease Designation for DIPG, and the FDA has officially indicated that Oblato would be eligible for a Rare Pediatric Disease Priority Review Voucher.