On July 6, 2021 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported that the Company held a Type A meeting with the U.S. Food and Drug Administration (FDA) during the second quarter of 2021 to discuss the deficiencies raised in the Complete Response Letter (CRL) received in February (Press release, Athenex, JUL 6, 2021, View Source [SID1234584604]).

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At the meeting, Athenex provided additional analyses, including overall survival (OS) data on patient subgroups, to provide a more comprehensive summary of the risk/benefit assessment. Athenex also proposed to collect additional OS data that could inform the design of a new clinical study.

The FDA was supportive and encouraged the Company to continue development of oral paclitaxel and encequidar for the treatment of metastatic breast cancer. The FDA also agreed that a well-designed and well-conducted trial may adequately address the deficiencies raised in the CRL. Athenex is evaluating the optimal design for a new clinical study which it intends to present to the FDA in the fourth quarter of 2021.

"We appreciate the FDA’s support for the development of oral paclitaxel and encequidar in this meeting and expect to maintain a collaborative dialogue on this program," said Dr. Rudolf Kwan, Chief Medical Officer of Athenex. "We continue to believe that, if approved, oral paclitaxel and encequidar has the potential to address a major unmet need in metastatic breast cancer. We hope to agree on a program that is capital efficient and will result in value creation for our stakeholders."

Athenex is also developing oral paclitaxel and encequidar for the treatment of cutaneous angiosarcoma, for which it has received Orphan Drug Designation from the FDA. Athenex also received Orphan Designations from the European Commission for oral paclitaxel and encequidar for the treatment of soft tissue sarcoma.

On July 6, 2021 APEIRON Biologics AG reported the start of a Phase Ib clinical trial with its product candidate APN401 for the treatment of solid tumors (Press release, Apeiron Biologics, JUL 6, 2021, View Source [SID1234584602]). The principle of cell therapy with APN401 by inhibiting the immune checkpoint Cbl-b aims at the patient’s own immune cells. These are modified to recognize and destroy cancer cells without being permanently genetically altered.

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The open-label, multi-center Phase Ib clinical trial is expected to enroll approximately 60 patients at multiple sites in Austria. The study objective is to evaluate the safety, tolerability and immunological effects of the treatment on patients with various solid tumors. This will build on the experience of the two previous Phase I clinical studies, which already successfully demonstrated good tolerability and the first signs of clinical efficacy by activating the immune cells that are crucial to tumor defense.

The clinical study is divided into two parts. Part A of the study aims to determine the optimal dosing, i.e. the quantity of treated cells reinfused back to the patient. Patients will receive APN401 treatment every three weeks. In part B of the study, patients with specific tumor indications (three groups of 15 patients each) will be treated to generate further efficacy signals, which will be used to determine the tumor indication for a subsequent Phase II clinical study. The Phase I clinical study will start at the Medical University of Vienna (MUW) where the GMP-certified production of the cell therapy and treatment of the patients will take place.

For the treatment, the patient’s own peripheral blood mononuclear cells (PBMCs) are collected, specifically modified outside the body using RNAi technology and then reinfused into the patient. APEIRON uses a specially developed system for this purpose, which enables an automated process from cell processing to reinfusion within just one day. This GMP-certified system increases patient safety and the reproducibility of the manufacturing process. APEIRON’s technology thus enables personalized cell therapy in solid tumors.

Peter Llewellyn-Davies, CEO of APEIRON Biologics AG, says: "We are thrilled to be contributing a groundbreaking cancer treatment with this truly pioneering step in development of our APN401 cell therapy. The short outpatient administration process, which can also be used for solid tumors, plays a key advantage compared to other autologous cell therapies. APN401 could offer critically ill patients, with previously difficult-to-treat cancers, new individualized treatment options and thus new hope. The APEIRON team is highly motivated to develop much needed new treatment options with this major next step."

Dr. Romana Gugenberger, Chief Medical & Scientific Officer (CMSO) of APEIRON Biologics AG, explains: "The immune system is the most effective weapon against tumor disease and offers many advantages over conventional therapies such as chemotherapy. Cbl-b is a master checkpoint in the immune system that controls important processes of the immune response, especially in cancer. APN401, by blocking Cbl-b using RNA interference (RNAi), is designed to reactivate the patient’s immune system, allowing it to fight solid tumors. The flexibility of RNAi technology could expand the applicability of cell therapy to additional immune checkpoints and holds enormous potential for new therapeutic approaches."

Prof. Dr. Nina Worel, Head of Cell Therapy at the Department of Transfusion Medicine at AKH / Medical University of Vienna and lead investigator of the study, adds: "Patients with advanced solid tumors urgently need new, safe and effective therapeutic options. Using cell therapy to enable the patient’s immune system to directly attack the tumor is a very promising approach. APEIRON’s APN401 could become superior in safety and efficacy to standard oncology therapies as well as to currently available cell therapies, due to its rapid applicability and central immune activation. We are excited to initiate this study here in Vienna and other sites and gain new insights."

About APN401
Immune checkpoints are receptors with immunoregulatory activity. Tumor cells can make use of these immune checkpoints to escape recognition by the immune system. Cbl-b represents a new class of intra-cellular immune checkpoints in contrast to the immune checkpoint molecules PD-1/PD-L1 and CTLA-4, which are localized at cell surfaces.

APN401, an autologous cell therapy, was designed to transiently, i.e. temporarily, inactivate Cbl-b ex-vivo in autologous PBMCs. These altered autologous PBMCs are then returned to the patient, with the entire procedure performed on an outpatient basis over one day. APN401 is well tolerated, has a good safety profile, and has shown early evidence of clinical activity in patients with advanced solid tumors in two Phase I studies

On July 5, 2021 BioMed X, a leading independent research institute, reported the start of its eighth joint research program with Merck KGaA, Darmstadt, Germany (Press release, Biomed x, JUL 5, 2021, View Source [SID1234584774]). The new program will explore the role of extrachromosomal DNA in cancer and it will complement the research of two ongoing oncology programs at BioMed X in the fields of DNA damage response and RNA splicing.

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Extrachromosomal circular DNA (ecDNA) was recently found to be particularly abundant in multiple human cancer cells, although its frequency varies among different cancer types. Elevated levels of ecDNA have been considered to be correlated with poor clinical outcome in human cancers.

"We are pleased to extend our collaboration even further in the field of cancer research," Christian Tidona, Founder and Managing Director of the BioMed X Institute said. "This new program will strengthen our expertise at the forefront of deep cancer biology which can potentially lead to better treatment options for patients."

The key aim of the new project will be to generate a comprehensive atlas of extrachromosomal DNA in human cancer tissues, to investigate how (onco)genes in ecDNA could contribute to tumorigenesis, disease progression, tumor heterogeneity, metastasis, and treatment resistance and to develop novel therapeutic strategies based on oncogenic alterations in ecDNA.

Further details about this call for application can be found on the website of the BioMed X Institute at www.bio.mx. Interested candidates are invited to apply via the BioMed X crowdsourcing platform at www.bio.mx/apply before August 29, 2021.

On July 5, 2021 Jazz Pharmaceuticals reported that it is flying high after hitting two back-to-back regulatory milestones late last month (Press release, Jazz Pharmaceuticals, JUL 5, 2021, View Source [SID1234584747]). The first was obtaining a seven-year Orphan Drug Exclusivity for Xywav, the latest contender from its array of treatments for daytime sleepiness. Then, days later, the Dublin-based biopharma announced notching a speedy FDA approval for its blood cancer drug.

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On June 30th, Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) was greenlighted as a component of a chemotherapy regimen designed for treating acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) in both children and adults. The drug received accelerated approval from the agency under the Real-Time Oncology Review (RTOR) program.

"We are excited to bring this important new treatment to patients who are in critical need, and we are grateful to FDA for the approval of Rylaze based on its established safety and efficacy profile. We are pleased Rylaze was approved before the trial is complete and are diligently working to advance additional clinical trial data," said Bruce Cozadd, Chairman, and CEO of Jazz Pharmaceuticals, in a statement.

"We are committed to quickly engaging with FDA to evolve the Rylaze product profile with additional dosing options and an IV route of administration."

L-Asparignase as an ALL Treatment

ALL is a rare type of blood cancer but still accounts for 30% of all cancers in children. In 1953, a discovery by Dr. John Graydon Kidd led to the widespread use of L-asparaginase as a treatment for ALL. It was found that the deprivation of the amino acid, L-asparagine, sends the leukemic cells into starvation mode, eventually killing them owing to the blockage in DNA, RNA, and protein synthesis.

Over the years, asparaginase derived from Escherichia coli was typically used as first-line therapy, but around two-thirds of patients were found to develop an allergic reaction. Such patients continued treatment with Erwinia chrysanthemi asparaginase.

Encouraging Trial Data

Rylaze is a recombinant erwinia asparaginase produced from a novel Pseudomonas fluorescens expression platform. The FDA approval was based on encouraging data from an ongoing Phase 2/3 trial that assessed the drug’s safety, tolerability, and efficacy. The study evaluated Rylaze in pediatric and adult patients with ALL or LBL who have had an allergic reaction to E. coli-derived asparaginases and have not previously received asparaginase from erwinia chrysanthemi.

Results from the first of three cohorts showed that patients who received 25 mg/m2 of Rylaze through intramuscular injection achieved intended levels of serum asparaginase activity, and nearly 94% of them maintained ≥ 0.1 U/mL of enzyme levels at 48 hours after administration.

"The accelerated development and approval of Rylaze marks an important step in bringing a meaningful new treatment option for many ALL patients – most of whom are children – who cannot tolerate E. coli-derived asparaginase medicine," said Dr. Luke Maese, Assistant Professor at the University of Utah, Primary Children’s Hospital and Huntsman Cancer Institute.

"Before the approval of Rylaze, there was a significant need for an effective asparaginase medicine that would allow patients to start and complete their prescribed treatment program with confidence in supply," he added.

Jazz reported total revenue of $2.36 Billion in 2020, of which $1,757.0 million was brought in by its combined oxybate business. Meanwhile, its total oncology net product sales accounted for $554.5 million. With the approval of some new oncology drugs, the company would be expected to exceed that number this year.

On July 5, 2021 Imugene Limited (ASX:IMU), a clinical stage immuno-oncology company, reported the company presented on the HER-Vaxx cancer immunotherapy program at the ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer 2021 Annual Meeting (Press release, Imugene, JUL 5, 2021, View Source [SID1234584745]).

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The abstract presentation was entitled ‘HERIZON: A PHASE 1B/2 OPEN-LABEL STUDY OF IMU-131 HER2/NEU PEPTIDE VACCINE PLUS STANDARD OF CARE CHEMOTHERAPY WITH RANDOMIZATION IN PHASE 2 IN PATIENTS WITH HER2/NEU OVEREXPRESSING METASTATIC OR ADVANCED ADENOCARCINOMA OF THE STOMACH OR GASTROESOPHAGEAL JUNCTION’ Updated Interim Analysis Results.

The presentation expanded on previously presented interim analysis data presented at AACR (Free AACR Whitepaper)2021.

To recap previously released results:
• Interim analysis in the randomized Phase 2 study showed statistically significant overall survival Hazard Ratio (HR) of 0.418 (80% 2-sided CI: 0.186, 0.942); HER-Vaxx showed a reduced risk of death of 58.2% in the HER-Vaxx plus chemotherapy group as compared to chemotherapy alone.
• The median overall survival (OS) for patients receiving HER-Vaxx plus chemotherapy was 14.2 months, compared to 8.8 months in patients treated with chemotherapy alone.
• The Phase 2 data represent a clinical proof-of-concept signal for HER-Vaxx when added to chemotherapy and indicate that B-cell activating immunotherapy vaccines can induce clinically active antibody responses.
• Recruitment of the Phase 2 trial was completed in January 2021.

The ESMO (Free ESMO Whitepaper) presentation highlights and presents the following new data:
• HER-Vaxx treatment resulted in a 50% Overall Response Rate (ORR) compared to 29% in patients treated with chemotherapy alone. The ORR measures the percentage of patients who responded to treatment with a partial response (PR) or better. 2 IMUGENE LIMITED ACN 009 179 551
• Treatment with HER-Vaxx clearly demonstrates patients develop high levels of HER2-specific antibodies early in the treatment protocol and are maintained during treatment and maintenance phase with only a few booster injections.
• Tumour response is correlated with the amount of antibody levels. Patients with antibody levels higher than 1050ng/ml received greater than 50% tumour reduction and may serve as a potential biomarker.
• In contrast to patients on chemotherapy alone, the reduction of tumour size is substantially higher in patients that received HER-Vaxx + chemotherapy.

Overall, this data demonstrates HER-Vaxx may provide treatment benefits consistent with traditional monoclonal antibodies with a corresponding adaptive immune response without added toxicity.

Imugene’s HER-Vaxx is a B-cell activating cancer immunotherapy designed to treat tumours that overexpress the HER-2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. The immunotherapy is constructed from several B cell epitopes derived from the extracellular domain of HER2/neu. It has been shown in pre-clinical studies and in Phase 1 and 2 studies to stimulate a potent polyclonal antibody response to HER-2/neu, a well-known and validated cancer target.