On July 12, 2022 Byondis B.V., an independent, Dutch clinical stage biopharmaceutical company creating precision medicines, reported that the U.S. Food & Drug Administration (FDA) accepted the company’s submission of a Biologics License Application (BLA) for [Vic-] Trastuzumab Duocarmazine (SYD985) in patients with HER2-positive unresectable locally advanced or metastatic breast cancer (MBC) (Press release, Byondis, JUL 12, 2022, View Source;trastuzumab-duocarmazine-syd985-in-her2-positive-metastatic-breast-cancer-301584658.html [SID1234616634]). The company has been given a Prescription Drug User Fee Act (PDUFA) action date of May 12, 2023.

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SYD985 is an investigational next generation anti-HER2 antibody-drug conjugate (ADC) that was granted fast track designation by the FDA in January 2018 based on promising Phase I data involving heavily pretreated last-line HER2-positive MBC patients (SYD985.001/NCT02277717).

"Women with HER2-positive breast cancer generally have a more aggressive disease, greater likelihood of recurrence and poorer prognosis," said Byondis Chief Medical Officer Jan Schellens, M.D., Ph.D. "Today’s SYD985 BLA acceptance by the FDA is an important step forward toward our goal of providing a much-needed alternative for these patients."

In HER2-positive breast cancer, overexpression of the human epidermal growth factor receptor 2 (HER2) protein causes out-of-control reproduction of breast cells. Less than 20 percent of all breast cancers are HER2-positive, with younger women being the most affected.1

"With our proprietary technologies, we aim to offer antibody-drug conjugates with a novel mechanism-of-action, which are still efficacious when other ADC therapies have been exhausted," said Byondis CEO Marco Timmers, Ph.D. "SYD985 combines a HER2-targeting antibody with a novel and potent cytotoxic drug in a way that limits damage to healthy tissue."

This is Byondis’ first regulatory submission for its lead program SYD985. The BLA is supported by data from the pivotal Phase III TULIP multi-center, open-label, randomized clinical trial comparing SYD985 to physician’s choice (PC) treatment in patients with pre-treated HER2-positive unresectable locally advanced or metastatic breast cancer (SYD985.002/NCT03262935). The study, of which the results were presented at the 2021 ESMO (Free ESMO Whitepaper) Congress, met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement of 2.1 months over PC. TULIP also demonstrated supportive overall survival (OS) results.

[Vic-]Trastuzumab Duocarmazine (SYD985), a Next Generation Antibody-Drug Conjugate

[Vic]-trastuzumab duocarmazine (SYD985) incorporates Byondis’ distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine. The ADC is comprised of the anti-HER2 monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA).

The antibody part of trastuzumab duocarmazine binds to HER2 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD985 is considered a form of targeted therapy.

ByonZine, Byondis’ Distinctive, Proprietary Linker-Drug Technology

While earlier generation ADCs improved targeting and cell killing, they were unstable in the bloodstream, leading to premature release of the cytotoxic payload, impacting healthy tissue and narrowing the therapeutic window. Byondis’ next generation ADCs are highly stable in circulation and carry an intricate, inactivated and potent cytotoxic drug that rapidly self-destructs if it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window.

Byondis’ differentiated linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.

The distinctive design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower HER2 expression may improve the efficacy potential, the so-called bystander effect.

On July 12, 2022 Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a late-stage biopharmaceutical company developing and commercializing first-in-class critical care products, reported that the Company held a Type B pre-BLA meeting with the U.S. Food and Drug Administration (FDA) to discuss I/ONTAK (denileukin diftitox), an engineered IL-2-diphtheria toxin fusion protein for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) (Press release, Citius Pharmaceuticals, JUL 12, 2022, View Source [SID1234616633]). I/ONTAK is a purified and more bioactive formulation of previously FDA-approved ONTAK. The pre-BLA meeting was held with representatives from the FDA’s Center for Drug Evaluation and Research (CDER).

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The purpose of the pre-BLA meeting with the FDA was to discuss the content and acceptability of the Company’s anticipated BLA for I/ONTAK. The briefing document provided to the FDA included a review of clinical and non-clinical studies and previous meeting minutes with the FDA.

"We appreciate the FDA’s continued guidance on the development path of a more purified formulation of ONTAK. Based on the FDA’s pre-BLA meeting comments, we intend to move forward with our planned BLA submission for I/ONTAK in the second half of 2022. We look forward to continued engagement with the FDA as we advance this program to provide CTCL patients with a potential new treatment option," stated Leonard Mazur, Chairman and CEO of Citius.

About I/ONTAK
I/ONTAK is a recombinant fusion protein that combines the interleukin-2 (IL-2) receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. I/ONTAK, a purified version of denileukin diftitox, is a reformulation of previously FDA-approved oncology treatment ONTAK. ONTAK was marketed in the U.S. from 1999 to 2014, when it was voluntarily withdrawn from the market. Manufacturing improvements resulted in a new formulation, which maintains the same amino acid sequence but features improved purity and bioactivity. The new formulation received regulatory approval in Japan for the treatment of CTCL and PTCL. In 2011 and 2013, the FDA granted orphan drug designation (ODD) to I/ONTAK for the treatment of PTCL and CTCL, respectively, making it potentially eligible for seven years of market exclusivity post-approval for each indication.

About Cutaneous T-cell Lymphoma
Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and Sézary Syndrome (SS) comprise the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle through multiple systemic agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients qualify, there is currently no curative therapy for advanced CTCL. Approximately 3,000 new cases are reported in the United States every year, with an estimated 30,000 – 40,000 individuals living with the disease.

On July 12, 2022 Mission Bio, Inc., the pioneer in high-throughput single-cell DNA and multi-omics analysis, reported the launch of solid tumor assays through its Pharma Assay Development (PAD) services (Press release, Mission Bio, JUL 12, 2022, View Source [SID1234616632]). The availability of this new service offering will help to accelerate the development of cancer therapeutics by reducing the time and cost associated with the characterization of solid tumor cells.

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Precision therapeutics for solid tumors have been historically bottlenecked due to technical challenges associated with the ability to deeply profile thousands of individual cells for a rich characterization of tumor evolution and heterogeneity. This must be done at a much higher resolution compared to bulk next-generation sequencing to enable detection of rare events, at a much earlier stage before progression.

Utilizing Mission Bio’s Tapestri platform, the company’s PAD services for solid tumors partner with researchers to provide high-resolution data to unmask the underlying genetic diversity across cell populations. Insights into the clonal landscape and co-occurrence of mutations enable improved patient stratification for clinical trials and the identification of druggable targets for precision therapeutics. Researchers can also monitor treatment resistance by analyzing the acquisition of rare mutations driving tumor progression over the course of treatment.

The expansion of Mission Bio’s PAD services to solid tumor research comes just three months after the launch of the Solid Tumor Solution on the Tapestri Platform, demonstrating Mission Bio’s commitment to continuously developing innovative single-cell technologies for its pharma customers.

"We have seen tremendous uptake and interest from top-tier pharma companies for our blood cancer Pharma Assay Development program, and we expect the same momentum for our solid tumor services," said Todd Druley, MD, PhD, Chief Medical Officer of Mission Bio. "With our solid tumor services, Mission Bio partners with pharma customers to elucidate the mechanisms of drug resistance through mutation acquisition, determine how cells transform from benign to malignant states, and reveal the genomic changes enabling cancer cells to metastasize – without having to bring single-cell technology or resources in-house. From a customer’s perspective, it is as easy as shipping out samples and getting a fully analyzed report back."

Mission Bio’s PAD services deliver comprehensive support across the therapeutic development process. The company has a dedicated team that works with researchers to develop assays, identify high-impact samples, and analyze the data. As part of the service, pharma partners have access to Mission Bio’s innovative technology, assay development team, R&D organization, and bioinformatics support.

For more on Mission Bio and the Tapestri platform, please visit missionbio.com.

On July 12, 2022 Bridge Biotherapeutics (KQ288330), a South Korean clinical-stage biotechnology company focused on developing novel drugs for cancer, fibrosis and inflammation, reported that interim clinical data from an ongoing Phase I study of BBT-176 has been selected for a mini oral presentation at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (IASLC WCLC 2022), Aug. 6-9 in Vienna (Press release, Bridge Biotherapeutics, JUL 12, 2022, View Source [SID1234616631]).

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The oral presentation, to be delivered by Sun Min Lim, M.D., Ph.D., assistant professor at Yonsei University College of Medicine, will discuss interim clinical data from the Phase I study of BBT-176 in advanced non-small cell lung cancer (NSCLC) patients harboring an EGFR mutation who were previously treated with at least one epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). According to the published abstract, the presentation will cover potent anti-tumor efficacy of BBT-176 explored with radiological improvements in both target and non-target lesions from two patients harboring EGFR triple mutations of exon 19 del/T790M/C797S.

One patient from the 320mg dosing cohort exhibited 30.3 percent shrinkage of the target lesion, according to the abstract. Another patient from the 480mg dosing cohort exhibited 26.3 percent shrinkage of the target lesion. Investigators will explore the recommended Phase 2 dose (RP2D) based on the overall safety, efficacy and tolerability information collected in the Phase 1 clinical study.

The abstract for the presentation (MA07.09) is now available at https://bit.ly/3uv2StQ.

Session and Presentation Information
Title: BBT-176, a 4th-generation EGFR TKI, for Progressed NSCLC after EGFR TKI Therapy: PK, Safety and Efficacy from Phase 1 Study
Session Title: Overcoming Resistance to EGFR Inhibitors
Session Number: MA07.09
Presentation Session: August 8, 2022, 12:52 pm CET
Presenting Author: Sun Min Lim, M.D., Ph.D., Yonsei University College of Medicine
Session Discussant: Pasi A. Jänne, M.D., Ph.D., Dana-Farber Cancer Institute

On July 12, 2022 GenScript ProBio (Brian Ho-sung Min, CEO), a global CDMO, and ACT Therapeutics (Seogkyoung-Kong, CEO), developing next-generation chimeric antigen receptor (CAR)-T cell therapy platform targeting solid cancer, reported that they had entered into a strategic partnership MOU concerning the development of a new CAR-T cell therapies (Press release, GenScript, JUL 12, 2022, View Source [SID1234616630]). GenScript ProBio and ACT Therapeutics have agreed to strengthen their cooperation in the cell therapy field through this MOU.

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GenScript ProBio and ACT Therapeutics are in the process of signing a contract for plasmid and virus vector development and production for the first pipeline of ACT Therapeutics’ Advanced CAR-T Platform (ACT platform), which will also be commissioned to produce raw materials for ACT Therapeutics’ subsequent pipeline.

With this agreement, GenScript ProBio has become a global partner that can support ACT platforms for ACT therapeutics.

The ACT platform is an immune cell-based next-generation cell and gene therapy technology that uses virus vectors to insert genes designed to target cancer antigens into immune cells. GenScript ProBio has a high-quality virus vector process development and one-stop service platform for GMP production required for cell and gene therapy development.

ACT Therapeutics’ ACT platform, is an advanced CAR-T technology that has a next-generation structure beyond the second-generation CAR-T cell therapy targeting existing blood cancer by overcoming the immune suppression microenvironment of solid cancer and activating surrounding immune cells. And various studies have secured animal experimental data on the efficacy and safety of the ACT platform, and confirmed the therapeutic characteristics while remaining in the immunosuppressive microenvironment of solid cancer and it complements the shortcomings of the existing second-generation CAR-T, which makes it competitive technology for solid cancer.

ACT therapeutics is a Korean bio venture company that has received initial investment through DAYLI Partners, Korea’s leading bio and healthcare venture capital since its establishment in 2020, and has been recognized for its technology such as receiving pre-series A investment in Samho Green Investment. Currently, investment consultations are underway with securities firms and venture capital to attract Series A investment

Brian H. Min, CEO of GenScript ProBio, said, "We are very happy to cooperate with ACT therapeutics in strategic partnership, and we are looking forward to support ACT Therapeutics’ ACT platform as a global partner through our accumulated technology."

Seogkyoung-Kong, CEO of ACT Therapeutics, said, "We have completed preparations for the ACT platform to emerge globally through a strategic partnership with GenScript ProBio. We will accelerate the development of treatments targeting refractory and intractable solid cancers."