On July 12, 2022 -mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported initiation of its first clinical trial with a SADA construct (Press release, Y-mAbs Therapeutics, JUL 12, 2022, View Source [SID1234616613]). This Phase 1 multicenter basket trial targets malignant melanoma, sarcoma and small cell lung cancer. The trial will have three parts: Part A with dose-finding for the SADA molecule and testing of dosing intervals between the protein and the 177Lu-DOTA payload, Part B will determine the optimal dose of 177Lu-DOTA, and Part C will be evaluating safety and initial signals of efficacy using repeated dosing. The Company expects a total of approximately 59 patients at 6-10 U.S. sites to be included in the trial.

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The GD2-SADA construct was created using our SADA technology, which was licensed by the Company from Memorial Sloan Kettering Cancer Center ("MSK") and Massachusetts Institute of Technology ("MIT") in April 2020. The SADA technology utilizes a pre-targeted payload delivery method where antibody constructs assemble in tetramers and bind to the tumor target. Unbound constructs predictably disassemble into smaller antibody fragments and are excreted through the kidneys within hours after administration. In a second infusion, a radioactive payload binds to the antibody constructs attached to the tumor target in order to radiate the tumor. This provides the possibility of targeting tumors with precision while minimizing radiation of normal tissues. We believe that the SADA technology platform can deliver a variety of payloads and could potentially be developed against multiple tumor targets, as well as for theragnostic purposes.

"The FDA acceptance of the IND for GD2-SADA marks an important milestone towards our mission of developing novel SADA treatments as we continue to execute our clinical development strategy for our pipeline of SADA constructs for the treatment of cancers with unmet medical need," said Thomas Gad, founder, President and Interim CEO. "We are seeing significant partnership interest for the SADA technology and we believe we are well-positioned to leverage the SADA platform as we move forward. We are truly excited about the potential of the SADA technology, which has already shown great promise, and we believe that it can further unlock the potential of radiolabeled therapeutics in tumors that have not historically demonstrated meaningful responses to radiolabeled agents."

Researchers at MSK, including Dr. Cheung, developed the SADA technology for radioimmunotherapy, which is exclusively licensed by MSK to Y-mAbs. Dr. Cheung has intellectual property rights and interests in the technology, and as a result of this licensing arrangement, MSK has institutional financial interests in the technology and in Y-mAbs.

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 Leap Therapeutics, Inc. (NASDAQ: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, and BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and acc688235ess for patients worldwide, reported the initiation of Part C of the ongoing DisTinGuish study to evaluate DKN-01, Leap’s anti-SSEDickkopf 1 (DKK1) antibody, in combination with tislelizumab, BeiGene’s anti-PD-1 antibody, and chemotherapy compared to a tislelizumab and chemotherapy control arm, in patients with gastric or gastroesophageal junction cancer (G/GEJ) (Press release, Leap Therapeutics, JUL 12, 2022, View Sourcenews-releases/news-release-details/leap-therapeutics-announces-initiation-new-dkn-01-clinical" target="_blank" title="View Sourcenews-releases/news-release-details/leap-therapeutics-announces-initiation-new-dkn-01-clinical" rel="nofollow">View Source [SID1234616615]).

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Additionally, Leap is initiating a new company-sponsored trial of DKN-01 in combination with standard of care bevacizumab and chemotherapy in second-line patients with colorectal cancer that is designed to expand into a randomized study. Leap is also supporting an investigator-initiated trial of DKN-01 plus pembrolizumab in patients with endometrial cancer to be conducted at The University of Texas M.D. Anderson Cancer Center and at the University of Alabama at Birmingham.

Leap’s management team, together with key opinion leaders, will host an R&D Day today to provide updates on the Company’s DKN-01 program including G/GEJ, colorectal cancer, endometrial cancer, and prostate cancer.

"Since the presentation of the data for DKN-01 plus tislelizumab and chemotherapy in first-line G/GEJ patients demonstrating compelling overall response rates and progression-free survival, Leap and BeiGene have been working together to create an optimal global strategy for this unique combination therapy. We are excited to enhance the development program and our collaboration with BeiGene through a randomized controlled trial in first-line patients, with a focus on those patients whose tumors express high levels of DKK1," said Douglas E. Onsi, President and Chief Executive Officer of Leap.

"Based on our clinical and preclinical data, Leap is committed to developing DKN-01 aggressively in multiple indications," said Cynthia Sirard, MD, Chief Medical Officer of Leap. "Through a strategic review and prioritization process, we have decided to initiate a company-sponsored study in second-line colorectal cancer patients of DKN-01 in combination with standard of care bevacizumab and chemotherapy. We will also support an investigator-initiated study in endometrial cancer patients of DKN-01 in combination with pembrolizumab, building on previous data showing single-agent activity of DKN-01."

R&D DAY:
Leap’s management team will host an R&D Day today at 12:00 p.m. Eastern Time and will be joined by key opinion leaders:

Samuel Klempner, MD, Associate Professor at Harvard and Massachusetts General Hospital;
Zev Wainberg, MD, Co-Director of the GI Oncology Program at University of California Los Angeles;
Rebecca Arend, MD, Assistant Professor at University of Alabama at Birmingham Comprehensive Cancer Center; and
David Wise, MD, PhD, Assistant Professor at NYU Langone Health.

The live webcast presentation of the R&D Day can be accessed by registering at View Source A replay of the event will be available for a limited time and may be accessed on the Investors page of the Company’s website at View Source

GASTRIC CANCER
The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. Part C of the DisTinGuish study will enroll approximately 160 first-line, HER2-negative patients who have had no prior therapy for unresectable locally advanced or metastatic G/GEJ adenocarcinoma. Patients will be randomized 1:1 to study DKN-01 in combination with tislelizumab and SOC chemotherapy, compared to tislelizumab and SOC chemotherapy. The primary objective of Part C is progression-free survival (PFS) in patients whose tumors express high levels of DKK1 (DKK1-high). Secondary objectives of Part C include PFS in all patients regardless of DKK1 expression, as well as overall survival (OS) and objective response rate (ORR) as measured by RECIST v1.1 in DKK1-high and all patients.

Part A and Part B of the DisTinGuish study are currently being conducted in the United States and the Republic of Korea. Part A enrolled 25 first-line HER2- G/GEJ cancer patients. As of December 10, 2021, the median PFS for all patients in Part A was 10.7 months, with 11.9 months PFS for DKK1-high patients, and the ORR for all patients who had completed a full cycle of therapy was 68%, with 90% ORR for DKK1-high patients. Part B of the study has enrolled 51 patients with second-line DKK1-high G/GEJ cancer. Additional follow-up data from Part A is expected to be presented in the third quarter 2022 and from Part B in the fourth quarter 2022.

COLORECTAL CANCER
The DeFianCe study is a Phase 2 study of DKN-01 in combination with bevacizumab and SOC chemotherapy in patients with advanced colorectal cancer who have received one prior systemic therapy. The study is designed with an initial 20 patient cohort and to then expand into a 130 patient randomized controlled trial against bevacizumab and SOC chemotherapy. The primary objective is PFS. Secondary objectives include ORR, duration of response (DOR), and OS. The study is expected to enroll its first patient in the third quarter 2022.

ENDOMETRIAL CANCER
The investigator-initiated trial of DKN-01 in combination with pembrolizumab is an open-label, Bayesian design, Phase 2 trial and will initially enroll 15 patients each into DKK1-high and DKK1-low cohorts. If the efficacy criteria is met in either or both of the 15 patient cohort(s), then the cohort(s) will be expanded by an additional 15 patients. The primary objective of the study is ORR. Secondary objectives include clinical benefit rate (CBR), PFS, OS, and DOR. The study is expected to enroll its first patient in the fourth quarter 2022.

Leap has previously studied DKN-01 as a monotherapy and in combination with paclitaxel in patients with endometrial cancer. In the group of 23 patients treated with DKN-01 monotherapy for whom DKK1 expression data was available, patients with DKK1-high tumors achieved 1 complete response and 1 partial response, along with greater ORR (25% vs. 0%), CBR (63% vs. 7%), and median PFS (4.3 months vs. 1.8 months [HR 0.26; 95 CI: 0.09, 0.75]) compared to patients with DKK1-low tumors. In the group of 24 patients treated with DKN-01 plus paclitaxel, 72% of whom had received three or more prior systemic therapies, DKK1-high patients had improved median PFS (5.4 months vs. 1.8 months [HR 0.34; 95% CI: 0.12, 0.97]) compared to DKK1-low patients.

ABOUT DKN-01
DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways and has an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immune suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells. The U.S. Food and Drug Administration has granted DKN-01 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.

ABOUT THE LEAP/BEIGENE COLLABORATION
Leap is conducting the DisTinGuish study as part of an exclusive option and license agreement with BeiGene for the development of DKN-01 in Asia (excluding Japan), Australia, and New Zealand. Leap retains exclusive rights for the development, manufacturing, and commercialization of DKN-01 for the rest of the world.

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 June 12, 2022 LegoChem Biosciences Inc. (LCB) and Glycotope GmbH (Glycotope) reported that they have signed a Research Collaboration and License Agreement to develop an antibody drug conjugate (ADC) by combining LCB’s proprietary ADC technology with one of Glycotope’s investigational tumor targeting antibodies (Press release, Glycotope, JUL 12, 2022, View Source [SID1234616599]).

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Under the terms of the agreement LCB has the right to exercise its option for worldwide exclusive rights to develop and commercialize the selected antibody as ADC, upon successful completion of a feasibility study. If LCB exercises these rights, Glycotope will receive an upfront payment as well as development and sales milestone payments plus royalties. Specific financial terms have not been disclosed.

"Through this collaboration, once the candidate ADC is discovered and nominated, Glycotope and LCB plan to advance this very innovative program to clinical stage as a competitive cancer therapy," said Dr. Yong-Zu Kim, CEO & President of LCB. "We are very pleased that companies with innovative antibody platforms, such as Glycotope have recognized the advantages of LCB’s linker-payload technology, which has been proven to be plasma stable as well as cancer-selectively activated."

"This exciting collaboration with LegoChem further underlines the value of Glycotope’s unique technology platform and strengthens our leading position in the development of highly specific glyco-epitope targeting antibodies," added Henner Kollenberg, CEO, Glycotope.

"Our antibodies are designed to deliver increased tumor selectivity. Combining these with LCB’s ADC technology platform offers the opportunity to develop ADCs with potential to perform beyond today’s best standard of care," said Patrik Kehler, CSO, Glycotope.

ADCs are a type of targeted cancer medicine that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. LCB’s ADC platform technologies overcome the existing limitations of ADCs by imparting a trinity of improved properties, (1) site-specific stable bioconjugation (2) cancer selective linker activation and (3) cancer-selective activation of potent payload, all of which in a significantly broader Therapeutic Window.

Glycotope’s antibodies target specific tumor-associated carbohydrate structures or protein/carbohydrate combined glyco-epitopes (GlycoTargets). Targeting these specific antigens enables broad indication range, long-term treatment potential and reduced on-target/off tumor toxicity, key elements of highly potent therapies. Based on this unrivalled tumor-specificity, Glycotope’s antibodies are highly suitable for a multi-function platform approach with independent modes of action to provide a tailored therapy format for as many patients as possible.