Metagenomi to Present Preclinical In Vivo and Ex Vivo Gene-Editing Data at the 63rd American Society of Hematology (ASH) Annual Meeting

On December 8, 2021 Metagenomi, a genetic medicines company with a versatile portfolio of next-generation gene editing tools, reported that the company will share data related to their novel, compact, and hypo-immune gene editing systems at the 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), which is taking place in Atlanta, GA and virtually, December 11–14 (Press release, Metagenomi, DEC 8, 2021, View Source [SID1234596619]).

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"The development of CAR T therapies and other genetically engineered cell therapies in recent years has resulted in significant benefits for patients, yet there remains a large unmet need for gene editing systems that can be used to develop novel immunotherapy approaches to treat blood cancers," said Brian C. Thomas, PhD, CEO and Co-Founder of Metagenomi. "At ASH (Free ASH Whitepaper), we are presenting data on our novel nucleases that display highly efficient and specific gene editing both in vivo and ex vivo and hold significant potential to drive the development of new and efficacious therapies for patients."

In a poster titled "A Novel Type V CRISPR System with Potential for Genome Editing in the Liver," it is shown that Metagenomi’s novel Type V CRISPR-associated nuclease was highly active in the liver of mice when systemically administered via lipid nanoparticles (LNP). The nuclease was derived from a unique natural environment and is phylogenetically distinct from previously identified Type V systems. Moreover, no antibodies to the nuclease were detected in serum from 50 healthy human donors, while between one third and half of the same serum samples contained antibodies that bind to spCas9, which is derived from a Streptococcus bacteria that commonly infects humans. In summary, this novel Type V CRISPR-associated nuclease is a promising new gene editing system for in vivo editing of the liver.

In a separate poster titled "Novel CRISPR-Associated Gene Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genomic Engineering for Cell Therapy Development," three novel gene editing systems were used to make reproducible and efficient edits to human immune cells, demonstrating utility for the next generation of cell therapy development for blood cancers. Metagenomi’s novel gene editing systems were used to disrupt the T cell receptor alpha-chain constant region and the T cell receptor beta-chain constant region in approximately 90 percent of cells. Beta-2 microglobulin was edited in 95 percent of T cells. A chimeric antigen receptor (CAR) construct was also shown to be integrated in up to 60 percent of T cells. Novel gene editing systems were deployed in NK cells to disrupt CD38 — a cell surface immune modulator that can be targeted in the development of cancer immunotherapy — and to integrate a CAR construct that led to robust CAR-directed cellular cytotoxicity. B cell editing occurred in approximately 80% of target cells with successful transgene integration. What’s more, as these gene editing systems are taken from environmental samples as opposed to human pathogens, pre-existing immunity is expected to be rare. In summary, these novel systems were shown to result in highly efficient and specific gene edits in human immune cells and display the potential for use in cell therapy development.

Details of the presentations are below:

Presentation Title: A Novel Type V CRISPR System with Potential for Genome Editing in the Liver
Session Title: 801. Gene Therapies: Poster I
Presenting Author: Morayma Temoche-Diaz, PhD
Publication Number: 1862
Session Time: Saturday, December 11, 5:30 p.m. ET

Presentation Title: Novel CRISPR-Associated Gene-Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genome Engineering for Cell Therapy Development
Session Title: 801. Gene Therapies: Poster III
Presenting Author: Gregory Cost, PhD, Vice President of Biology, Metagenomi
Publication Number: 3984
Session Time: Monday, December 13, 6:00 – 8:00 p.m. ET

Shasqi Awarded a Second NCI Grant of $1.9M to Accelerate the Development of SQ3370

On December 8, 2021 Shasqi, a clinical-stage biotechnology company developing precision activated oncology therapeutics with its proprietary Click Activated Protodrugs Against Cancer (CAPAC) Platform, reported that it has been awarded a second ‘Direct to Phase 2’ Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI) (Press release, Shasqi, DEC 8, 2021, View Source [SID1234596618]). The $1.9 million grant will support a Phase 1b dose-expansion cohort in the company’s ongoing development program for its click-activated prodrug therapy, SQ3370. The safety and efficacy data from this cohort will support dose selection for the planned Phase 2 study of SQ3370 in patients with advanced soft tissue sarcoma.

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"The NCI has made two investments in our Phase 1 clinical studies of SQ3370, which will enable us to accelerate the development of SQ3370 and gather additional efficacy and safety data to inform our Phase 2 clinical trial design. We are grateful for the vision of the NCI and their support of SQ3370 and our click chemistry platform," said José M. Mejía Oneto, M.D., Ph.D., Founder and CEO of Shasqi. "The early data from our Phase 1 study of SQ3370 provides initial validation for our platform in humans, with an encouraging safety profile and initial hints of clinical activity. We believe we can improve the efficacy, safety, and biological effects of many existing cancer therapies and various modalities which are currently either too toxic to be used widely, have significant safety burden, or have limited efficacy due to a limited therapeutic window."

About CAPAC and SQ3370:

SQ3370 is the first click chemistry-based treatment to be tested in humans, and utilizes Shasqi’s proprietary CAPAC platform, an approach that activates cancer drugs at a tumor with decreased systemic toxicity. Shasqi is validating its platform with SQ3370, which is designed to activate a powerful chemotherapeutic, doxorubicin, at the site of the tumor. The investigational product is based on the chemical reaction between a drug protected through a trans-cyclooctene modification (a protodrug) and a tetrazine-modified biopolymer. The biopolymer is injected into the target tumor lesion, where it precisely activates an intravenously infused protodrug. Shasqi believes its click-chemistry approach can improve the efficacy and safety of many existing drugs and various modalities that have a limited therapeutic window.

Cytovia Therapeutics’ Scientific Leadership to Present at Upcoming Conferences

On December 8, 2021 Cytovia Therapeutics, Inc., a biopharmaceutical company developing allogeneic "off-the-shelf" gene-edited iNK cells (NK cells derived from induced pluripotent stem cells, or iPSCs), CAR (Chimeric Antigen Receptor)-iNK cells, and Flex-NK cell engager multifunctional antibodies, reported that its scientific leadership will present at the following upcoming conferences (Press release, Cytovia Therapeutics, DEC 8, 2021, View Source [SID1234596617]):

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"We are proud of the scientific thought leadership of our colleagues Drs. Frankel, Li, and Kadouche, who will present Cytovia’s latest advances"

iPSC-Derived Cell Therapies Summit (Virtual Event)

Wednesday, December 8th, 2021, 9.30 AM
Demonstrating Safety & Efficacy of iPSC-derived Cells to Maximize Clinical Translation
(Industry Leaders’ Fireside Chat: Paving the Way For the Future of Cell Therapy with iPSCs)
Featuring Cytovia Therapeutics CMO Stanley Frankel

Wednesday, December 8th, 2021, 3PM
Advancing Clinical Trial Strategy for Successful Clinical Outcomes
(Developing iPSC-Derived NK Cell Therapies Against Solid Tumors)
Featuring Cytovia Therapeutics CSO Wei Li

Antibody Engineering & Therapeutics Conference (San Diego, California)

December 12th-15th, 2021
Dr. Jean Kadouche, Cytovia Therapeutics scientific co-founder and Global Head of Antibody R&D, will present the "Design, Manufacturing, and Activity of FLEX Immune Cell Engager Multi-functional Antibodies" poster on behalf of the Cytovia team.

"We are proud of the scientific thought leadership of our colleagues Drs. Frankel, Li, and Kadouche, who will present Cytovia’s latest advances," said Dr. Daniel Teper, CEO of Cytovia Therapeutics. "Cytovia is committed to translating disruptive innovation in cell therapy to create therapeutics that advance towards a cancer cure. Cytovia is the first biotech company to develop its own best-in-class gene-edited, iPSC-derived NK cells and NK Engager antibodies, with the potential to combine them for optimal clinical outcomes in both hematological and solid tumors."

Amphera progresses two pancreatic cancer programmes after encouraging initial safety and efficacy data in mesothelioma

On December 8, 2021 Amphera B.V., a late-stage biotechnology company developing MesoPher cell therapy to treat cancer, reported that significant progress in its two clinical programs in pancreatic cancer as well as the full recruitment of all patients in its pivotal Phase II/III study in mesothelioma (Press release, Amphera, DEC 8, 2021, View Source [SID1234596616]).

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Based on a preliminary efficacy analysis of the first cohort of the REACtiVe study in resected pancreatic cancer patients, an expansion cohort has been completed at a remarkable pace with results expected in H2 2022. In total 26 patients are now included in the study. Safety and efficacy data from the first cohort of the REACtiVe study in resected pancreatic cancer patients treated with MesoPher have been submitted for publication by Erasmus MC, Rotterdam, the Netherlands.

In addition a study in metastatic pancreatic cancer, REACtiVe-2, has started recruiting patients. This study will assess the safety and efficacy of a combination therapy of MesoPher and mitazalimab (a CD40 agonist from Alligator Bioscience). This follows the strong preclinical data published in the Journal for ImmunoTherapy of Cancer, which established the potency of the combination (available here).

Finally, the company announces that the Phase II/III pivotal study DENIM in mesothelioma patients is fully recruited and confirms the readout to be expected in Q4 2022.

Rob Meijer, CEO of Amphera said: "Over the last year Amphera has made exceptional progress with its clinical development programmes based on its MesoPher cell therapy platform. Despite the challenging pandemic environment, our trials saw strong enrolment, underlying the high medical need for patients. The pivotal Phase II/III DENIM study in pleural mesothelioma has now been fully recruited with the read-out expected in Q4 2022 and we are strongly encouraged by the rapid enrolment of the expansion cohort of the Phase II REACtiVe study in pancreatic cancer. In addition to the studies in pancreatic cancer and pleural mesothelioma, efficacy of MesoPher is investigated in abdominal mesothelioma and pleural mesothelioma in combination with surgical resection."

Prof. Joachim Aerts MD PhD, Medical Advisor to Amphera said: "Efficacy was first proven in mesothelioma and for me, as a clinician and a scientist, it is exciting to see that the previous efficacy found, translates into relevant clinical results for patients in other indications, especially one with a dire prognosis such as pancreatic cancer. We have also recently published highly compelling long-term survival data in Vaccines from three studies in mesothelioma patients (available here). In the three studies combined, the median overall survival was 27 months and the overall survival at 5 years was 21%. The expanding data set is showing the real potential of MesoPher in a wide range of oncology indications."

FoundationOne®CDx Receives FDA Approval as a Companion Diagnostic for BRAF Inhibitor Therapeutics in Melanoma

On December 8, 2021 Foundation Medicine, Inc. reported that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOneCDx to be used as a companion diagnostic for two groups of current and future FDA-approved therapeutics in melanoma, which includes BRAF inhibitor monotherapies targeting BRAFV600E and BRAF/MEK inhibitor combination therapies targeting BRAFV600E or V600K mutations (Press release, Foundation Medicine, DEC 8, 2021, View Source [SID1234596615]). This approval makes FoundationOneCDx the only comprehensive genomic profiling (CGP) test approved as a companion diagnostic across two groups of targeted therapies, representing an important step toward simplifying decision making for oncologists.

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Melanoma is a serious form of skin cancer that accounts for an estimated 207,790 cases each year.1 BRAF mutations are the most common type of mutation in melanoma and are present in more than half of all melanoma cases.2 As a companion diagnostic for therapies targeting BRAFV600E and BRAFV600K mutations in melanoma, FoundationOneCDx offers oncologists flexibility when selecting the right therapy for their melanoma patients and ensures all treatment options are considered within these groups of therapies.

"As the first group therapy approval for any comprehensive genomic profiling test, this milestone reinforces our dedication to pioneering advances that expand the power of genomic testing in cancer care," said Mia Levy, MD, PhD, chief medical officer at Foundation Medicine. "This approval will allow oncologists to uncover all possible FDA-approved treatment options for these indications through just one test, providing more insights for physicians and patients, more efficiently than ever before."

This approval represents an innovative, more efficient regulatory approach that simplifies the companion diagnostic approval process for biopharma companies developing BRAF inhibitor therapeutics, while maintaining rigor and high-quality standards.

The first new therapeutics for which FoundationOneCDx is a companion diagnostic under the group approvals are Pfizer’s BRAFTOVI/MEKTOVI and Novartis Tafinlar (dabrafenib) + Mekinist (trametinib) combination therapeutics. Moving forward FoundationOneCDx will automatically become a companion diagnostic for future BRAF inhibitors that are approved by the FDA under these groups.

About FoundationOne CDx

FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. FoundationOne CDx is for prescription use only and is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit View Source