On May 24, 2022 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported positive topline results from the DeFi trial, a double-blind, placebo-controlled Phase 3 trial evaluating the efficacy, safety and tolerability of nirogacestat, an investigational oral gamma secretase inhibitor, in adult patients with progressing desmoid tumors (Press release, SpringWorks Therapeutics, MAY 24, 2022, View Source [SID1234614978]).

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The DeFi trial met its primary endpoint of improving progression-free survival (PFS), demonstrating a statistically significant improvement for nirogacestat over placebo, with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p < 0.001). In addition, the trial met all key secondary endpoints, with nirogacestat demonstrating statistically significant improvements as compared to placebo in objective response rate (ORR) and patient-reported outcomes (PROs). Nirogacestat was generally well tolerated with a manageable safety profile. The majority of women of childbearing potential had adverse events consistent with ovarian dysfunction. Other adverse events were generally consistent with previously reported data.

Additional data are expected to be presented at an upcoming medical conference in the second half of 2022 and SpringWorks plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second half of 2022.

"Desmoid tumors are aggressive soft-tissue tumors that can lead to severe negative outcomes for patients, including long-lasting pain, disfigurement, and amputation. In rare cases, when vital organs are impacted, desmoid tumors can also be life-threatening," said Saqib Islam, Chief Executive Officer of SpringWorks. "Today’s announcement represents a significant milestone towards our goal of bringing the first approved therapy to the desmoid tumor community. We look forward to sharing the DeFi trial data with the FDA and to presenting detailed study results at a medical meeting later this year."

Nirogacestat has received Orphan Drug Designation from the FDA for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy Designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.

About the DeFi Trial

DeFi (NCT03785964) is an ongoing, global, randomized (1:1), double-blind, placebo-controlled Phase 3 trial evaluating the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The study randomized 142 patients to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by >20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to the first dose of study treatment. The primary endpoint is progression-free survival, as assessed by blinded independent central review. Secondary and exploratory endpoints include safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes (PROs).

About Desmoid Tumors

Desmoid tumors are rare, aggressive, locally invasive, and potentially morbid tumors of the soft tissues.1,2 While they do not metastasize, desmoid tumors are associated with a high rate of recurrence.2,3,4 Sometimes referred to as aggressive fibromatosis, or desmoid fibromatosis, these soft tissue tumors can be serious, debilitating, and, in rare cases when vital organs are impacted, they can be life-threatening.2,5

Desmoid tumors are most commonly diagnosed in patients between the ages of 20 to 44 years, with a two-to-three times higher prevalence in females.4,6,7 It is estimated that there are 1,000-1,650 new cases diagnosed per year in the United States.7,8

Historically, desmoid tumors were treated with surgical resection, but this approach has become less favored due to a high recurrence rate after surgery.1,4,9 There are currently no FDA-approved therapies for the treatment of desmoid tumors.

About Nirogacestat

Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.

In addition, gamma secretase has been shown to directly cleave membrane-bound B cell maturation antigen (BCMA), resulting in the release of the BCMA extracellular domain, or ECD, from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma. SpringWorks is evaluating nirogacestat as a BCMA potentiator and has eight collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, two CAR T cell therapies, three bispecific antibodies and a monoclonal antibody. SpringWorks has also formed research collaborations with Fred Hutchinson Cancer Research Center and Dana-Farber Cancer Institute to further characterize the ability of nirogacestat to modulate BCMA and potentiate BCMA-directed therapies using a variety of preclinical multiple myeloma models.

Conference Call Details

SpringWorks will host a conference call and webcast today, Tuesday, May 24, 2022, at 8:30 a.m. Eastern Time to discuss the DeFi trial data. Participants can listen to the call by dialing +1 (844) 946-0285 (domestic) or +1 (602) 585-9676 (international) and providing the conference ID 2268304. A live webcast presentation can be accessed through the Investors & Media section of the Company’s website at View Source A replay of the webcast will be available on the SpringWorks website for a limited time following the event.

On May 24, 2022 Enveric Biosciences, Inc. (NASDAQ: ENVB) ("Enveric" or the "Company"), a neuroscience-focused biotechnology company developing next-generation, psychedelic-inspired mental health medicines, reported that Avani Kanubaddi, President and Chief Operating Officer of Enveric, will participate virtually in Microdose’s Psychedelic Capital: May 2022 Conference to be held virtually on May 26, 2022 (Press release, Enveric Biosciences, MAY 24, 2022, View Source [SID1234614977]).

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Mr. Kanubaddi will participate on a panel "The Spinoffs – Divide and Conquer" on Thursday, May 26th at 4:05 p.m. ET. The panel will discuss the latest spinoffs among publicly traded companies to stay competitive, honor the shareholders and combat the markets. Register to attend here.

For more information about the conference, or to schedule a one-on-one meeting with Enveric’s management team, please send an email to KCSA Strategic Communications at [email protected].

On May 24, 2022 Calidi Biotherapeutics, Inc., a clinical-stage biotechnology company pioneering the development of stem cell-based delivery of oncolytic viruses, reported that it has been granted a new patent (No. US 11,285,194, Combination immunotherapy approach for treatment of cancer) by the U.S. Patent and Trademark Office (USPTO) related to its proprietary SuperNova (SNV) technology platform (Press release, Calidi Biotherapeutics, MAY 24, 2022, View Source [SID1234614974]). The enhanced oncolytic virotherapy delivery platform was designed to provide and improve therapeutic treatments for multiple cancer indications. Calidi’s product candidates are in the early stages of development and have not yet been approved by the U.S. Food and Drug Administration (FDA).

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The SNV platform is composed of allogeneic, adipose-derived mesenchymal stem cells (AD-MSC) loaded with an oncolytic agent, such as the vaccinia virus, and is anticipated to be used in combination with various immunotherapy agents, including blocking antibodies. The SNV platform is designed to shield oncolytic viral payloads from the immune system, thereby efficiently delivering immuno-oncology therapy directly to tumor sites.

"Calidi’s Supernova platform has been developed through years of research in stem cell delivery and potentiation of oncolytic viruses and has the potential to revolutionize the treatment of solid tumors," said Allan J. Camaisa, CEO and Chairman of Calidi. "The addition of this patent further strengthens our intellectual property position and solidifies the opportunity to use our platform technology in advancing therapeutic discovery and development through the FDA approval process."

The Calidi approach aims to induce a durable anti-tumor immune response. In pre-clinical studies, Calidi’s SNV platform-based product candidates have been shown to shield the oncolytic viruses from destruction by the patient’s immune system, supporting efficient viral replication within the stem cells prior to delivery to tumor sites. Once there, the viral payload selectively destroys tumor cells and stimulates the patient’s immune system to attack the tumor.

"Our outstanding team of doctors and scientists have invested years of intensive research and groundbreaking work to develop Calidi’s SNV platform technology," said Boris Minev, M.D., President, Medical and Scientific Affairs at Calidi, and a patent inventor. "This patent represents the culmination of their impressive expertise, dedication, and passion, and will help the company continue to advance its novel discovery programs."

On May 24, 2022 Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune and inflammatory diseases, reported that the U.S. Food and Drug Administration (FDA) has removed the partial clinical hold placed on its NEON-2 trial evaluating davoceticept (ALPN-202), a first-in-class conditional CD28 costimulator and dual checkpoint inhibitor, in combination with pembrolizumab in adults with advanced malignancies (Press release, Alpine Immune Sciences, MAY 24, 2022, View Source [SID1234614973]).

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The FDA removed the hold after review of the Company’s Complete Response, which included a comprehensive review of the davoceticept safety database, as well as a revised investigator brochure and study protocol. As previously disclosed, under the terms of the hold, previously enrolled participants continued to receive study drug, but no new participants could be enrolled until the partial clinical hold was removed. The ongoing NEON-1 study was not subject to the hold.

About Davoceticept (ALPN-202)

Davoceticept (ALPN-202) is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor intended for the treatment of cancer. Preclinical studies of davoceticept have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. NEON-1 (NCT04186637), a Phase 1 monotherapy dose escalation and expansion trial in patients with advanced malignancies, has completed dose escalation and is currently enrolling its expansion cohorts. NEON-2 (NCT04920383), a combination study of davoceticept (ALPN-202) and pembrolizumab, was initiated in June 2021.

On May 24, 2022 LUMICKS, a leading life science tools company that develops instruments for dynamic single-molecule and cell avidity analysis, reported the publication in Cancer Cell of preclinical research identifying "Avidity Enhancement" as a new strategy to improve therapeutic outcome of Chimeric Antigen Receptor (CAR) T cell immunotherapy in Acute Myeloid Leukemia (AML) (Press release, LUMICKS, MAY 24, 2022, View Source;utm_medium=rss&utm_campaign=avidity-enhancement-new-strategy-for-improving-car-t-therapy [SID1234614972]).

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AML poses significant clinical challenges due to its resistance to therapies and its bleak prognosis. Approximately 20,000 people in the US and 300,000 worldwide die from AML every year, making it the most common form of acute leukemia in adults and a major public health issue.

The Cancer Cell paper (May 9, 2022), entitled "Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia," was authored by a team of CAR T cell researchers led by Dr. Marcela V. Maus, Associate Professor of Medicine at Harvard Medical School and Director of the Cellular Immunotherapy program at Massachusetts General Hospital.

The study details a novel strategy for better cancer treatment with CAR T cells for AML. "Avidity Enhancement", increasing cell-cell binding from both the tumor and CAR T cell side, led to a more effective eradication of tumors in mouse models of AML. In this paper, data generated using the LUMICKS z-Movi Cell Avidity Analyzer provided superior correlation with CAR T cell activity in vivo compared to the standard in vitro assays in assessing the potency of CAR variants.

Building upon previous research from the Maus Lab indicating ‘avidity escape’ as an evasion mechanism when CAR T cell therapies are deployed against solid tumors, "avidity enhancement" is a promising strategy for improving clinical success of CAR T therapies.

"We continue to be excited about the pivotal research emerging from The Maus Lab and other leading laboratories that demonstrates how researchers can leverage the technological and scientific power of measuring cell avidity with the z-Movi Cell Avidity Analyzer," said Andrea Candelli, PhD, Chief Scientific Officer of LUMICKS. "This work further solidifies the idea that cell avidity can be a unique biomarker to improve the selection of CAR T therapies for superior therapeutic outcomes in hematological malignancies as well as in solid tumors. We are delighted to collaborate with researchers worldwide in uncovering meaningful new insights, such as the new treatment approaches suggested for AML contained in this new paper in Cancer Cell."

The z-Movi Cell Avidity Analyzer measures cell avidity, or level of binding, between immune cells and their targets, enabling researchers to identify the most potent immunotherapeutic effector cells. This unique technology provides predictive, reproducible, and fast results at single-cell resolution. LUMICKS’ cell avidity solutions use acoustics to measure forces and interactions between cells, with the goal of shortening the drug development cycle of immunotherapies and reducing failure rates in clinical trials. First introduced in 2020, the z-Movi is being rapidly adopted by academic and biopharma laboratories around the world.

About the Study Findings

Unlike other forms of leukemia, AML has been notoriously difficult to successfully target using CAR T cells. Researchers believe this is due to both low expression of the antigenic targeted protein on the cancer cells and unstable expression of activating receptors on the T cells.

In this publication, the researchers have shown that increasing avidity of the CAR T cells to their target cells leads to enhanced tumor killing in vitro as in mouse models. Target protein expression on the cancer cells was chemically enhanced using available therapeutics and/or changing the design of the CAR to stabilize its expression on the T cells. Through this method, the researchers show that enhancing cell avidity for therapeutic efficacy can be achieved by modulating the tumor cell or modulating the surface of the T cell. Either strategy increased the sensitivity of the tumor to CAR T mediated clearance, confirming cell avidity as a crucial biomarker in immune oncology.