On August 16, 2022 SHINE Technologies, LLC (SHINE), a next-generation fusion technology company, reported Tom D’Orazio has joined as the CEO of Phoenix LLC (Phoenix) (Press release, Shine Medical Technologies, AUG 16, 2022, View Source [SID1234618510]). SHINE and Phoenix are both wholly owned subsidiaries of Illuminated Holdings, and Phoenix operates the industrial imaging arm of the business. D’Orazio succeeds Jess Giffey, who served as interim CEO and will continue in her role as General Manager of SHINE’s Systems & Manufacturing division.

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D’Orazio brings more than two decades of experience in sales leadership roles for start-ups, emerging and established companies across health care, biotech and software industries. He most recently was the Chief Operating Officer for Tryp Therapeutics, a clinical-stage pharma company, where he was also a founding member. Prior to Tryp, he was CEO and President at ImmnoPrecise Antibodies, a scientific services and research organization.

D’Orazio’s leadership experience spans strategic planning, corporate partnerships, fundraising, and building sales and marketing teams.

"As a proven leader for science-driven companies, Tom will be a great addition to Phoenix," said Greg Piefer, Founder and CEO of SHINE. "Along with the announcement of a contract with the Department of Homeland Security earlier this year, Phoenix has signed several new imaging contracts this year. With his leadership and experience, Tom will continue to build on that momentum. I’d also like to thank Jess for serving as interim CEO for the past year."

"I’m delighted to be back in Wisconsin and working on growing an innovative service enterprise," D’Orazio said. "The advanced technology and opportunity to help create a safer world through neutron imaging is both inspiring and exciting. I’m anxious to meet the talented team and get to work."

D’Orazio holds a bachelor’s degree in chemistry from Loyola University of Chicago and an MBA from Vanderbilt University with concentrations in marketing and finance.

On August 16, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported that the Israeli Ministry of Health (MOH) authorized the initiation of a company-sponsored Phase I/II clinical trial designed to evaluate the safety, tolerability and preliminary efficacy of Allocetra alone, and in combination with a PD1 checkpoint inhibitor, in patients with advanced solid tumors (Press release, Enlivex Therapeutics, AUG 16, 2022, View Source [SID1234618454]).

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Einat Galamidi, M.D., Vice President, Medical of Enlivex, stated, "With Allocetra treatment, we aim to change the balance of macrophage populations surrounding the solid tumor environment in favor of anti-cancer activity in order to overcome the biological mechanisms underlying checkpoint inhibitor resistance. Collaborative studies with Yale Cancer Center have generated meaningful preclinical data, suggesting we may be successful in these efforts, with Allocetra and an anti-PD1 agent synergistically combining, which delivered a statistically significant survival benefit in a murine model of ovarian cancer. We aim to build on these results in our upcoming Phase I/II trial and are pleased that the Israeli Ministry of Health has cleared it for initiation."

The planned Phase I/II trial is a multicenter, open-label, dose escalation trial that is expected to enroll up to 48 patients with advanced solid tumors across two trial stages. Stage 1 of the trial will examine escalating doses of Allocetra monotherapy administered intravenously (IV) or intraperitoneally (IP) once a week for three consecutive weeks. Stage 2 will evaluate escalating doses of Allocetra administered IV or IP and combined with anti-PD1 therapy. Patients in Stage 2 will receive three injections of Allocetra concomitantly with the studied anti-PD1 agent. The primary objective of the study is to evaluate safety and tolerability throughout the treatment period and through one week after the last administration of Allocetra. Key secondary endpoints include efficacy assessments, such as best overall response rate, progression-free survival, and overall survival. Changes in immune cell/cytokine profiling in peritoneal fluid will also be assessed as an exploratory endpoint.

The planned study population will be adult patients with advanced, unresectable or metastatic solid tumors that have relapsed or have been refractory to available approved therapies, or patients who are not eligible for, or have declined additional standard-of-care systemic therapy.

Though commercially successful, checkpoint inhibitors have limited efficacy in many cancers, with a 2019 study estimating less than 13% of all U.S. cancer patients responded to these therapies1. This limited efficacy of checkpoint inhibitors in certain solid cancers is linked to tumor mechanisms that facilitate the recruitment of macrophages which become "pro-tumor" tumor associated macrophages (TAMs). The TAMs typically form a physical layer on top of the solid tumor and induce immunosuppression in the solid tumor microenvironment. This hampers the ability of immune cells, which are the effectors of checkpoint inhibitor therapy, to efficiently attack the tumor cells. Moreover, TAMs promote tumor growth and metastasis through various additional mechanisms that contribute to poor clinical outcomes and response to therapy. Previously reported preclinical data from solid tumor models suggest that Allocetra has the potential to reprogram pro-tumor macrophages back to their homeostatic state and may thereby promote disease resolution and enhance the efficacy of checkpoint inhibitors and other immunotherapeutic agents.

REFERENCE

1. Haslam A, Prasad V. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs. JAMA Netw Open. 2019 May 3;2(5):e192535. doi: 10.1001/jamanetworkopen.2019.2535. PMID: 31050774; PMCID: PMC6503493.

ABOUT ALLOCETRA

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On August 16, 2022 Beijing’s SinocellTech reported that its anti-CD20 McAb, ripertamab, proved non-inferiority to Genentech’s rituximab (Rituxan) in a China Phase III trial (Press release, Sinocelltech, AUG 16, 2022, View Source [SID1234618453]). The trial enrolled 364 patients with primary diffuse large B-cell lymphoma (DLBCL) . The Objective Response Rate was 94% in both cohorts with safety events also very similar. In 2018, SinocellTech out-licensed rights for ripertamab to CSPC Pharma in a deal worth up to $98 million plus sales milestones. SinocellTech’s pipeline consists of 23 products including 21 novel differentiated drugs and two biosimilars.

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On August 16, 2022 Prescient Therapeutics (ASX: PTX), a clinical stage oncology company developing personalised cancer therapies, reported that it has entered a manufacturing services agreement with specialist cell therapy manufacturer, Q-Gen Cell Therapeutics (Q-Gen), to produce its OmniCAR cell lines for upcoming clinical trials, with initial work now commenced (Press release, Prescient Therapeutics, AUG 16, 2022, View Source [SID1234618443]).

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As Prescient advances the development of its next-generation OmniCAR programs for acute myeloid leukemia (AML); Her2 positive solid cancers and glioblastoma multiforme, the encouraging progress of the OmniCAR AML program makes it likely be the first OmniCAR program to enter clinical studies.

Manufacturing will take place at Q-Gen’s dedicated Brisbane facility, which produces autologous and allogeneic cell therapies for local and international pharmaceutical companies and academic research groups. Q-Gen is the cell therapy manufacturing arm of the QIMR Berghofer Medical Research Institute and is one of Australia’s leading producers of cell-based medicines. Prescient has commenced the technology transfer process for OmniCAR-T cell manufacturing.

CAR-T therapies involve isolating T cells from a cancer patient and inserting new genetic material into them so that they express a new chimeric antigen receptor capable of recognising cancer cells, before being re-infused into the patient. By contrast, OmniCAR T cells will express a universal immune receptor (SpyCatcher), which can bind with any separate SpyTagged targeting ligand. Thus, OmniCAR cells can potentially address any cancer by incorporating binders to any cancer antigen. This modularity also enables other important and novel characteristics to overcome limitations faced by conventional CAR-T therapies, including post-infusion control of T cell activity and antigen re-direction.

This agreement with Q-Gen covers production and delivery of autologous OmniCAR-T cells for clinical trials. Material conditions of the contract include transduction of T cells with SpyCatcher lentivirus; arming of OmniCAR T cells with SpyTagged binders; and associated quality measures. This agreement will also incorporate CellPryme-M into the manufacturing process of OmniCAR T cells. The agreement lasts up to 5 years, with provision for earlier cessation or extension as per typical commercial terms.

Q-Gen’s General Manager, Andrew Masel, commented "We are excited to be working with Prescient Therapeutics on what we see as a unique cell therapy platform. The team at Q-Gen is looking forward to working closely with Prescient to produce the product for clinical trials here at the QIMR Berghofer Medical Research Institute."

Prescient’s CEO and Managing Director Steven Yatomi-Clarke said, "Prescient is working steadily towards our first in human studies of OmniCAR, which will be an important milestone for the Company. This important agreement secures Prescient’s crucial supply of OmniCAR cells for our clinical trials and ensures we are producing the best possible cell therapy products for doctors and patients living with hardto-treat cancers."

In January Prescient received accreditation by the Office of the Gene Regulator enabling the company to conduct clinical trials in Australia involving gene-edited cells such as OmniCAR.

On August 16, 2022 Nektar Therapeutics (Nasdaq: NKTR) reported the publication of preclinical data in Blood Advances, the open-access journal of the American Society of Hematology (ASH) (Free ASH Whitepaper), highlighting the effects of NKTR-255, a novel polymer-conjugated human IL-15, on natural killer (NK) cell function and proliferation in multiple myeloma (MM) (Press release, Nektar Therapeutics, AUG 16, 2022, View Source [SID1234618438]).

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"These findings published today in Blood Advances demonstrate the promising anti-tumor activity of IL-15 in engaging natural killer cell biology in indications with immunosuppressive tumor microenvironments as in multiple myeloma," said Nikhil C. Munshi, MD, Professor of Medicine at Harvard Medical School, Director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. "Among other immune cells, the NK cell expansion and improved function induced by NKTR-255 is contributing to more effective control of multiple myeloma tumor growth, raising a potential scope for synergism with other anti-MM therapies such as anti-CD38 antibodies."

The Dana-Farber team analyzed in vitro pharmacological properties of NKTR-255 in engaging the IL-15 pathway and stimulating NK cells against MM cells. The research also looked at the anti-tumor activity of combining NKTR-255 with the anti-CD38 antibody, daratumumab, in vitro and in vivo.

"The published data demonstrate that NKTR-255 not only enhances antitumor responses of human NK cells against MM target cells, but also increases ex vivo expression of NK activating receptors and adhesion molecules. Furthermore, studies in a humanized MM mouse model show that NKTR-255 enhances in vitro antibody-dependent cellular cytotoxicity (ADCC) of NK cells and synergizes with daratumumab to reduce MM cell growth," said Mariateresa Fulciniti, Ph.D., the senior author on this manuscript at Dana-Farber. These preclinical findings support Nektar’s robust clinical development program for NKTR-255 and further evaluation of the novel immunotherapeutic approach in MM, alone or in combination with monoclonal antibodies or potentially with other immunomodulatory drugs.

Key findings are summarized below:

NKTR-255 enhances antitumor responses of myeloma derived human NK cells against MM target cells.
NKTR-255 enhances in vitro ADCC of NK cells and synergizes with daratumumab to reduce MM growth in humanized mouse model.
NKTR-255 increases ex vivo expression of NK activating receptors and adhesion molecules.
Augmenting NK cell number and functions shows effectiveness against MM cells in the context of their bone marrow milieu.
The full citation of this article can be accessed here.

About NKTR-255

NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body’s innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response.

Preclinical findings suggest NKTR-255 has the potential to synergistically combine with antibody-dependent cellular cytotoxicity molecules as well as to enhance CAR-T therapies. Nektar has initiated a Phase 1 dose escalation and expansion clinical study of NKTR-255 in adults with relapsed or refractory non-Hodgkin lymphoma or multiple myeloma, as well as a Phase 1/2 clinical study of NKTR-255 in patients with relapsed or refractory head and neck squamous cell carcinoma or colorectal cancer. Nektar is also continuing its oncology clinical collaboration with Merck KGaA and Pfizer Inc. to evaluate the maintenance regimen of NKTR-255 in combination with avelumab, a PD-L1 inhibitor, in patients with locally advanced or metastatic urothelial carcinoma in the Phase II JAVELIN Bladder Medley study. Nektar is also currently designing a Nektar- sponsored Phase II study combining NKTR-255 with approved CAR-T cell therapies in diffuse large B-cell lymphoma, which it aims to initiate in the first quarter of 2023.