On December 9, 2022 Prelude Corporation (PreludeDx), a leader in molecular diagnostics and precision medicine for early-stage breast cancer, reported study results demonstrating that DCISionRT provides patients with ductal carcinoma in situ (DCIS) superior recurrence risk stratification and radiation therapy (RT) benefit prediction compared to commonly used clinicopathologic (CP) features (Press release, PreludeDx, DEC 9, 2022, View Source [SID1234625000]). The data was presented in a spotlight presentation at the 2022 San Antonio Breast Cancer Symposium (SABCS).

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Until now, clinicians have relied upon clinicopathologic features alone, such as nuclear grade (NG), tumor size and age to determine which patients may not need radiation therapy.

This study, titled ‘7-gene Predictive Biosignature Improves Risk Stratification for Breast Ductal Carcinoma in Situ Patients Compared to Clinicopathologic Criteria, Identifying a Low-Risk Group Not Clinically Benefiting from Adjuvant Radiotherapy’, revealed in 926 women from four cohorts, that DCISionRT was a superior predictor of 10-year IBR rates and RT benefit compared to clinicopathologic criteria. DCISionRT identified that approximately half of CP-Low Risk patients were classified as elevated risk by the test and significantly benefited from RT with an absolute 17.7% reduction in 10-year ipsilateral breast recurrence. Whereas DCISionRT Low Risk patients, which included about one-third of CP High-Risk patients, had no significant RT benefit, representing a true low risk group.

"In the DCISionRT Low Risk group, I would have to treat approximately 100 patients to benefit just one patient. In contrast, in the DCISionRT High Risk group, I would have to treat approximately 6 patients to benefit one. This study further validates that the biosignature is far more accurate than using grade or other factors for determining DCIS outcomes," said Rachel Rabinovitch, MD, FASTRO, Professor of Radiation Oncology at University of Colorado. "Traditional methods result in the over-and-under treatment of DCIS. It is a very significant advancement to have a patient specific biosignature tool which predicts RT benefit."

"We are grateful for our prestigious physician-researchers around the world who are working tirelessly to further integrate and share the immense data and clinical value of DCISionRT in shared treatment decision making with DCIS patients," said Dan Forche, President and CEO of PreludeDx. "We are inspired by their enthusiasm and dedicated to continued innovation in the fight against early-stage breast cancer."

About DCISionRT for Breast DCIS
DCISionRT is the only risk assessment test for patients with ductal carcinoma in situ (DCIS) that predicts radiation therapy benefit. Patients with DCIS have cancerous cells lining the milk ducts of the breast, but they have not spread into surrounding breast tissue. In the US, over 60,000 women are newly diagnosed with DCIS each year. DCISionRT, developed by PreludeDx on technology licensed from the University of California San Francisco, and built on research that began with funding from the National Cancer Institute, enables physicians to better understand the biology of DCIS. DCISionRT combines the latest innovations in molecular biology with risk-based assessment scores to assess a woman’s individual tumor biology along with other pathologic risk factors and provide a personalized recurrence risk. The test provides a Decision Score that identifies a woman’s risk as low or elevated. Unlike other risk assessment tools, the DCISionRT test combines protein expression from seven biomarkers and four clinicopathologic factors, using a non-linear algorithm to account for multiple interactions between individual factors in order to better interpret complex biological information. DCISionRT’s intelligent reporting provides a woman’s recurrence risk after breast conserving surgery alone and with the addition of radiation therapy. In turn, this new information may help patients and their physicians to make more informed treatment decisions.

On December 9, 2022 Cytovia Inc.(DBA Cytovia Therapeutics, Inc.), a biopharmaceutical company focused on unlocking the power of natural killer (NK) cell therapeutics through bispecific antibodies and TALEN gene-edited, iPSC-derived NK (iNK) cells, reported new preclinical data for its CD38-targeted Flex-NK bispecific antibody at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s 64th Annual Meeting (ASH 2022) taking place in New Orleans, LA, and virtually December 10-13th, 2022 (Press release, Cytovia Therapeutics, DEC 9, 2022, View Source [SID1234624999]).

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"We’re delighted to see further progress on our CD38-targeted Flex-NK bispecific antibody program, with a pre-clinical package that supports clinical evaluation in 2023," commented Cytovia CEO Dr. Daniel Teper. "The data presented at ASH (Free ASH Whitepaper) suggests that CYT-338, our CD38-targeted Flex-NK Bispecific Antibody, has a differentiated profile compared to daratumumab, the leading CD38-targeted monoclonal antibody and that CYT-338 may have the ability to overcome NK cell exhaustion and dysfunction.

We believe that by redirecting and activating NK cells to kill myeloma cells, bispecific antibodies have the potential to offer new options for patients not responding to first lines of treatment."

Details about the ASH (Free ASH Whitepaper) poster presentation are as follows:

Title: Biological Characterization and Differential Gene Expression Analysis of CYT-338 NK Cell Engager (NKE) Against Multiple Myeloma (MM) Tumors
Abstract Number: 3142
Session Name: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster II
Date and Time: Sunday, December 11th, 2022 (6-8PM CST)
Location: Ernest N. Morial Convention Center, Hall D, New Orleans, LA

The poster is available online on both the Cytovia Therapeutics and American Society of Hematology (ASH) (Free ASH Whitepaper) websites.

The presentations show that Cytovia’s bispecific antibody CYT-338 demonstrated it could increase the ability of both its iPSC-derived (iNK) and Peripheral Blood (PBNK) Natural Killer cells to kill Multiple Myeloma (MM) tumor spheroids in a dose dependent manner that peaked 2-3 days following of initiation of killing. Serial killing activity of iNKs and PBNKs against MM tumors declined over additional rounds of killing but the combination with CYT-338 maintained serial killing at high levels suggesting the ability of CYT-338 to overcome NK cell exhaustion.

CYT-338 showed potent dose dependent ADCP against MM tumors indicating an additional effector cell pathway targeted by CYT-338 and dose dependent CDC against MM tumors demonstrating an additional cytotoxicity pathway targeted by CYT-338. Gene expression analysis of autologous patient NK cell and MM co-cultures treated with CYT-338 or daratumumab showed similar and distinct gene expression profiles. The distinct lymphocyte activation gene expression pathways activated by CYT-338 may contribute to the increased NK cell redirected cytotoxicity of MM tumors compared to daratumumab. The above results support further development of CYT-338 as a potent NK cell engager that could also activate macrophages and complement to mediate its anti MM tumor effects.

The data has been developed in collaboration with Lynx Bio, a clinical-stage biotechnology company combining physiologically relevant suspension cell co-culture assays, automated microfluidics, and deep learning analytics with the goal of rapidly advancing drug candidates in oncology and bringing personalized cancer treatments to patients.

About Multiple Myeloma
Multiple Myeloma is a currently incurable cancer, affecting a type of white blood cell known as plasma cells. It leads to an accumulation of tumor cells in the bone marrow, rapidly outnumbering healthy blood cells. Instead of producing beneficial antibodies, cancerous cells release abnormal proteins causing several complications. According to the World Cancer Research Fund, Multiple Myeloma is the 3rd most common blood cancer, with 176,404 new cases worldwide in 2020 including more than 50,000 cases in Europe, 35,318 in the US, and 31,890 in Eastern Asia. There have been more than 117,000 deaths worldwide in 2020 with a median overall survival of less than 12 month in patients refractory to standard of care.

Initial treatment comprises of a combination of different biological and targeted chemotherapies, and bone marrow transplants for eligible patients. Immunotherapy with monoclonal antibodies against CD38 such as daratumumab and isatuximab are the most rapidly growing treatment option. Antibody-drug conjugates and Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA and T-Cell Engager Bispecific Antibodies have recently been approved for Multiple Myeloma but high cost, limited product supply and the need for strict safety monitoring may limit their use.

On December 9, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for talquetamab for the treatment of patients with relapsed or refractory multiple myeloma (Press release, Johnson & Johnson, DEC 9, 2022, View Source [SID1234624998]). Talquetamab is an investigational, off-the-shelf (ready to use), bispecific T-cell engager antibody targeting both GPRC5D, a novel drug target that is on some normal cells but overexpressed on myeloma cells, and separately targets CD3 on T cells.1

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"Despite the therapies that have been developed for the treatment of multiple myeloma, there remains persistent unmet needs for patients who relapse or become refractory," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "Through our discovery and development of talquetamab, a novel GPRC5DxCD3 bispecific antibody, we remain relentlessly committed to the investigation of innovative therapies for patients and oncologists. We look forward to working closely with the FDA in their review of the talquetamab submission."

This BLA is supported by data from the Phase 1/2, first-in-human MonumenTAL-1 study of talquetamab (Phase 1: NCT03399799; Phase 2: NCT04634552) in patients with relapsed or refractory multiple myeloma who have received more than three prior lines of therapy.1 The first presentation of Phase 2 results from the MonumenTAL-1 study will be highlighted at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 10, 2022 in an oral scientific session (Abstract #157)2 and featured as part of the ASH (Free ASH Whitepaper) Press Briefing.

About Talquetamab
Talquetamab is a first-in-class, off-the-shelf (ready to use), investigational bispecific T-cell engager antibody targeting both GPRC5D, a novel multiple myeloma target, and CD3, a primary component of the T-cell receptor.1 CD3 is involved in activating T cells, and GPRC5D is highly expressed on multiple myeloma cells.3,4

Talquetamab, which is given by subcutaneous injection, is currently being evaluated in the Phase 1/2 MonumenTAL-1 clinical study for the treatment of relapsed or refractory multiple myeloma (NCT03399799), and in combination studies RedirecTT-1 (NCT04586426), TRIMM-2 (NCT04108195), TRIMM-3 (NCT05338775), MonumenTAL-2 (NCT05050097) and MonumenTAL-3 (NCT05455320).

Talquetamab received Breakthrough Therapy designation from the U.S. FDA in June 2022 for the treatment of adult patients with relapsed or refractory multiple myeloma, who have previously received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. In May 2021 and August 2021, talquetamab received an Orphan Drug designation for the treatment of multiple myeloma by the U.S. FDA and the European Commission, respectively. In January 2021, talquetamab received a PRIME designation by the European Commission.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.5 In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.6 In 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.7 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.

On December 9, 2022 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported that the publication of a new study in JCO Precision Oncology highlighting the clinical utility of its personalized and tumor-informed molecular residual disease test, Signatera, for postoperative risk stratification and prediction of recurrence in patients with stage I-III esophageal and gastric cancers (EGCs) (Press release, Natera, DEC 9, 2022, View Source [SID1234624997]). The full study can be found here.

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EGCs are the sixth most common cancers worldwide,1 affecting approximately 47,000 new patients per year in the U.S.2 In patients with localized disease, despite treatment with curative-intent therapy, over 50% recur within three years.3-5 Today, clinical practice guidelines support either adjuvant therapy or observation post surgery, so there is a strong unmet need for better risk stratification tools to help inform these risk-based management decisions. In addition, due to the high rate of recurrence, guidelines recommend frequent monitoring for recurrence with imaging, endoscopic evaluation or tumor markers.6

This real-world study, one of the largest reported EGC studies to date, included 943 plasma samples collected from 295 patients across more than 70 institutions. The primary analysis focused on the 212 patients with stage I-III disease. Signatera ctDNA status was evaluated at diagnosis (prior to neoadjuvant treatment), post surgery and then serially during routine surveillance, with median clinical followup of 417 days.

Key takeaways from the study include:

Pre-treatment: ctDNA was detectable in 96% (23/24) of patients with preoperative samples.
Post surgery (within 16 weeks): ctDNA was detected post-surgically in 23.5% (16/68) of patients. ctDNA-positive patients experienced a higher rate of recurrence (81.2%) in comparison to ctDNA-negative patients (13.5%). ctDNA-positive patients experienced inferior RFS (HR: 10.7, 95% CI: 4.3-29.3, p<0.0001).
Surveillance setting (at least 2 weeks after completion of adjuvant treatment): the recurrence rate in patients with a ctDNA-positive result was 95.2% (20/21) compared to 7.9% (5/63) in patients who remained ctDNA-negative. ctDNA-positive patients experienced inferior RFS (HR: 17.7, 95% CI: 7.3-50.7, p<0.0001).
Multivariate analysis: ctDNA was the strongest prognostic factor compared to all other clinicopathological risk factors including disease stage, location, and MSI status (HR: 11.82, 95% CI: 6.18-22.6, p<0.001).
"This study shows how longitudinal assessment using Signatera allows for accurate post operative risk stratification and adjuvant therapy or surveillance monitoring in patients with esophagogastric cancers in a real-world setting," said Samuel Klempner, M.D., associate professor at Massachusetts General Hospital and corresponding author of the study. "Unfortunately, many gastroesophageal cancers recur after definitive treatment, and patients with advanced disease have a poor prognosis. This study highlights the potential for Signatera to better identify patients at highest risk of recurrence and help develop novel treatment approaches."

About Signatera

Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use, and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. Signatera is intended to detect and quantify cancer left in the body, at levels down to a single tumor molecule in a tube of blood, to identify recurrence earlier and to help optimize treatment decisions.

On December 9, 2022 UroGen Pharma Ltd. (Nasdaq: URGN) a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported the grants of inducement restricted stock units ("RSUs") to 12 new employees in connection with their employment with UroGen (Press release, UroGen Pharma, DEC 9, 2022, View Source [SID1234624996]). These new team members will support the ongoing commercial launch of Jelmyto (mitomycin) for pyelocalyceal solution, UroGen’s first approved product, and the continued development of the Company’s pipeline.

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Up to 20,800 shares of UroGen’s common stock are issuable upon the vesting and settlement of the RSUs. The RSUs will vest equally over three years, with one third of the underlying shares vesting each year on the anniversary of the vesting date, subject in each case to the employee’s continued service relationship with UroGen.

The RSUs are subject to the terms and conditions of UroGen’s 2019 Inducement Plan and RSU grant notice and agreement thereunder. The RSU grants were granted as an inducement material to each employee entering into employment with UroGen in accordance with Nasdaq listing Rule 5635(c)(4).