On March 22, 2021 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company targeting diseased macrophages in patients with sepsis, COVID-19 and solid tumors, together with Yale Cancer Center, a National Cancer Institute-designated comprehensive cancer center, reported a research collaboration for the assessment of the potential of Allocetra to enhance the activity of checkpoint inhibitors in solid tumors (Press release, Enlivex Therapeutics, MAR 22, 2021, View Source [SID1234576961]). Allocetra is a macrophage-reprogramming immunotherapy product candidate currently in clinical development by Enlivex, as, among other things, a potential therapy in combination with approved immune checkpoint inhibitors for hard-to-treat solid tumors.

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Under the strategic collaboration, the parties intend to develop and execute pre-clinical programs to investigate the potential synergies between Allocetra and commercially-approved checkpoint inhibitor therapies for select solid cancers.

The Principal Investigator for this collaboration is Dr. Vish Muthusamy, PhD, Director of the Yale Center for Precision Cancer Modeling. Dr. Muthusamy is a cancer biologist with expertise in preclinical investigation of candidate cancer therapies. His center has developed in vivo tumor models to investigate pharmacological evaluation of drugs. Recently, Dr. Muthusamy worked in close collaboration several academic investigators and pharmaceutical companies to develop cancer therapeutics that are in various stages of clinical development. The collaboration’s scientific advisor is Dr. Marcus W. Bosenberg, MD, PhD, Co-Leader of the Genomics, Genetics and Epigenetics Program at Yale Cancer Center. On behalf of the Yale team, Dr. Bosenberg said "At Yale we have been interested in trying to understand the process of macrophage reprogramming for some time, and we are excited about studying the effects of Allocetra in potentially recruiting anti-tumor macrophages in the tumor environment and characterize the effects."

Dror Mevorach, M.D., Chief Medical Officer of Enlivex, commented, "We are excited to collaborate with the distinguished research and clinical teams at Yale. Allocetra may have a rebalancing effect on the typically immunosuppressive tumor microenvironment, potentially by facilitating the conversion of pro-tumor macrophage populations to anti-tumor populations. Together, we plan to investigate the potential of AllocetraTM to synergistically combine with commercially available checkpoint inhibitors for the treatment of solid tumors."

Oren Hershkovitz, Ph.D., CEO of Enlivex, stated, "We believe the researchers and clinicians at Yale are world-class and ideal partners as we work to realize Allocetra’s potential. We are pleased to formulate a strategic collaboration with Yale for the development of Allocetra as a potentially key component of combination therapies for solid tumors."

Allocetra is currently in clinical development for acute life-threatening immune-mediated diseases, such as sepsis and COVID-19. Enlivex recently reported positive top-line results in 21 patients from Phase Ib and Phase II investigator-initiated trials in COVID-19 patients in severe/critical condition. The Company has also previously reported positive results from a Phase Ib investigator-initiated trial in 10 sepsis patients and plans to initiate a controlled, randomized, Phase IIb study in sepsis during the first quarter of 2021.

On March 22, 2021 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical-stage immunotherapy company focused on the discovery and development of next generation therapeutics for cancer, reported that it will be added to the Russell 2000 Index effective March 22, 2021, as part of its quarterly initial public offering (IPO) additions (Press release, Sensei Biotherapeutics, MAR 22, 2021, View Source [SID1234576960]). The Russell 2000 Index measures the performance of the small cap segment of the U.S. equity market. Membership in the Russell 2000 provides automatic inclusion in the appropriate growth and value style indexes.

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The Russell U.S. Indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $9 trillion in assets are benchmarked against Russell U.S. Indexes. Russell U.S. Indexes are part of FTSE Russell, a leading global index provider. For more information about the Russell U.S. Indexes and the Russell Indexes reconstitution, visit the FTSE Russell website.

On March 22, 2021 Abeona Therapeutics Inc. (Nasdaq: ABEO), a fully-integrated leader in gene and cell therapy, reported that Michael Amoroso, Executive Vice President, Chief Operating Officer (COO) and principal executive officer at Abeona, has been promoted to President, Chief Executive Officer (CEO) and a member of the company’s Board of Directors, effective immediately (Press release, Abeona Therapeutics, MAR 22, 2021, View Source [SID1234576959]).

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"Michael’s promotion to CEO reflects his unwavering commitment and outstanding operational leadership during a period of important transition for the company, and the Board fully supports him and the Abeona senior management team," said Steven H. Rouhandeh, Chairman of Abeona’s Board of Directors. "Under Michael’s stewardship, Abeona has remained focused on the strategy of providing our novel gene and cell therapies to patients who currently have no approved treatment options, delivering on meaningful milestones across our three clinical development programs during the last six months."

Most recently, Mr. Amoroso has been responsible for overseeing the operational management of Abeona, including research and clinical development, regulatory, medical, commercial, corporate affairs and business development as COO and principal executive officer. Mr. Amoroso joined Abeona in 2020, bringing extensive experience in leading teams across clinical development, regulatory and medical affairs, corporate affairs, and commercial, both in the U.S and globally, with direct operational experience in major world markets. For 20 years, he has led and been part of teams responsible for launches and delivering profit and loss results for major biopharmaceutical products across most therapeutic areas. Mr. Amoroso has worked with companies in the small molecule, biologic, and cell and gene therapy spaces, with his deepest areas of expertise in rare oncological diseases.

Prior to joining Abeona, Mr. Amoroso held various senior level executive positions at leading biopharmaceutical companies, including Kite, Eisai Inc., Celgene Corporation (now a subsidiary of Bristol-Myers Squibb Company), and began his biopharmaceutical career at Aventis (now Sanofi). Mr. Amoroso earned his Executive M.B.A. in Management from the Stern School of Business, New York University, and his B.A. in Biological Sciences, summa cum laude, from Rider University.

On March 22, 2021 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported the presentation of clinical data from its Phase 2 clinical trial of DKN-01 as a monotherapy and in combination with paclitaxel in patients with advanced gynecological malignancies at the Society of Gynecologic Oncology 2021 Annual Meeting on Women’s Cancer, being held as a virtual meeting from March 19-25, 2021 (Press release, Leap Therapeutics, MAR 22, 2021, View Source [SID1234576958]). DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein, leading to the activation of the innate immune system in the tumor microenvironment and anti-tumor activity.

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"DKN-01 demonstrated objective responses, including a monotherapy complete response continuing now for over 2 and a half years, and durable tumor reductions as a single agent and in combination with paclitaxel in the advanced gynecologic cancer patients treated in the study," said Rebecca Arend, M.D., MSPH, Associate Professor, University of Alabama at Birmingham O’Neal Comprehensive Cancer Center. "The disease control rate and progression-free survival were strongest in patients whose tumors express high levels of DKK1 (DKK1-high), which is a group that real world evidence has shown to have poorer outcomes on other therapies."

"The activity of DKN-01 in this study was comparable to the monotherapy data from other widely-used immuno-oncology or targeted therapies." Dr. Arend continued. "As DKN-01 was extremely well tolerated, additional studies of DKN-01 as a monotherapy and in combination with anti-PD-1 antibody therapy are warranted in endometrial cancer patients with DKK1-high tumors."

The P204 Study in Advanced Gynecologic Cancers

The P204 study was a Phase 2 basket study evaluating DKN-01 as a monotherapy or in combination with paclitaxel in groups composed of epithelial endometrial cancer (EEC), epithelial ovarian cancer (EOC), or carcinosarcoma (MMMT) patients. The primary endpoint of the P204 study was overall response rate (ORR), and secondary endpoints include disease control rate (DCR) and progression-free survival (PFS). In each group, at least fifty percent (50%) of patients were required to have specified Wnt signaling pathway alterations, a subgroup of which (Wnt activating mutations) are known to drive high tumoral DKK1 expression. Tumoral DKK1 expression was determined retrospectively by RNAscope chromogenic in situ hybridization and correlated with clinical outcomes.

Key Findings from the P204 Study

One hundred-eleven patients were enrolled in the study, including 29 EEC patients in a DKN-01 monotherapy group, 24 EEC patients in a DKN-01 plus paclitaxel group, 14 EOC patients in a DKN-01 monotherapy group, 19 EOC patients in a DKN-01 plus paclitaxel group, 9 MMMT patients in a DKN-01 monotherapy group, and 16 MMMT patients in a DKN-01 plus paclitaxel group. The key findings from the study were:

·EEC patients and patients with Wnt activating mutations express higher levels of DKK1: EEC patients expressed higher levels of DKK1 and had a higher frequency of Wnt activating mutations than patients with EOC. Within EEC, patients with endometrioid histology had higher DKK1 expression than those with non-endometrioid histology. Patients whose tumors had Wnt activating mutations expressed 14.4 times higher levels of DKK1.

·DKN-01 has enhanced activity in patients whose tumors express high levels of DKK1: In the group of 22 EEC patients treated with DKN-01 monotherapy for whom DKK1 expression data was available, patients with DKK1-high tumors (n=7) had greater ORR (14% vs. 0%), DCR (57% vs. 7%), and median PFS (3.0 months vs. 1.8 months [HR 0.39; 95% CI: 0.14, 1.1]) compared to patients with DKK1-low tumors (n=15). Additionally, seven patients did not have DKK1 expression results available, of whom one had a complete response (14%) and five (72%) had a best response of stable disease, including three patients with Wnt activating mutations.

In the group of 24 EEC patients treated with DKN-01 plus paclitaxel, 72% of whom had received three or more prior systemic therapies, DKK1-high patients (n=11) 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 (n=9). Four patients did not have DKK1 expression data available.

·Within EEC, DKN-01 activity strongest in endometrioid histology: In the pooled group of 27 patients with endometrioid histology for whom DKK1 expression data was available, patients with DKK1-high tumors (n=14) had greater DCR (57% vs. 15%) and median PFS (4.1 months vs. 1.8 months [HR 0.34; 95% CI: 0.14, 0.81]) than patients with DKK1-low tumors (n=13). Additionally, seven patients with endometrioid histology did not have DKK1 expression results available, of whom one (14%) had a complete response and five (72%) had a best response of stable disease, including two patients with Wnt activating mutations.

Conference Call Details

Leap will be hosting a conference call today at 8:30 a.m. Eastern Time with Dr. Arend and members of Leap’s management team to discuss the data. The call can be accessed by dialing (866) 589-0108 (U.S. and Canada) or (409) 231-2048 (international). The passcode for the conference call is 2077923. The presentation will be webcast live and may be accessed on the Investors page of the company’s website at View Source, where a replay of the event will also be available for a limited time.

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, which have an important role in tumor cell signaling and in mediating an immuno-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.

On March 17, 2021 T-Cure Bioscience, Inc., a privately held company focused on developing T cell receptor (TCR) therapy products for the treatment of solid tumors, reported that the Company has entered into a clinical research agreement with Rutgers, The State University of New Jersey, to fund a Phase I clinical study testing a TCR-based product candidate for the treatment of tumors expressing Kita-Kyushu lung cancer antigen 1 (KK-LC-1), such as gastric, cervical, lung, and triple negative breast cancers (Press release, T-Cure Bioscience, MAR 22, 2021, View Source [SID1234576957]). T-Cure acquired the KK-LC-1 TCR therapy under an exclusive, worldwide license with the National Cancer Institute (NCI) in 2020. The Principal Investigator who will conduct the clinical research is Christian S. Hinrichs, M.D., Chief of the Section of Cancer Immunotherapy and Co-Director of the Cancer Immunology and Metabolism Center of Excellence at Rutgers Cancer Institute of New Jersey. Dr. Hinrichs is an expert in cancer immunology and immunotherapy and was recruited from the NCI where he served as Senior Investigator at the Genitourinary Malignancies Branch. T-Cure anticipates the KK-LC-1 TCR therapy will enter a multi-site Phase 1 clinical study in the second quarter of 2021 at the NCI, with the clinical study responsibilities to be transferred to Rutgers in the second half of 2021.

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"I joined the Cancer Immunology and Metabolism Center of Excellence because I believe that Rutgers Cancer Institute can be a global leader in cancer and tumor immunology research and development. In support of that mission, I am excited to partner with T-Cure to launch the first cell therapy clinical trial targeting the KK-LC-1 antigen," stated Dr. Hinrichs. "I began collaborating with the T-Cure team on this T cell receptor therapy while at the NCI, and I am pleased to continue working with them to advance this therapy at Rutgers."

"We look forward to our partnership with Dr. Hinrichs at Rutgers as a continuation of the work we undertook with him and his team at the NCI to advance this novel TCR product candidate through preclinical and clinical development," stated Gang Zeng, Ph.D., Chief Executive Officer of T-Cure. "The TCR was isolated from the tumor-infiltrating lymphocytes of a patient who had a complete response to a safely administered immunotherapy. Accordingly, we believe it holds great promise for engineering patients’ immune cells to effectively target and destroy cancer cells without being harmful to healthy tissue."