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H3 Biomedicine Presents Investigational Data Update on H3B-6545 for Treatment of Locally Advanced or Metastatic Estrogen Receptor- positive, HER2-negative Breast Cancer at San Antonio Breast Cancer Symposium

On December 8, 2021 H3 Biomedicine Inc. (H3), a U.S.-based precision medicine research & development subsidiary of Eisai Co., Ltd., reported the presentation of two posters at the 2021 San Antonio Breast Cancer Symposium (SABCS) being held in a hybrid format on December 7- 10, 2021 (Press release, H3 Biomedicine, DEC 8, 2021, View Source;positive-HER2-negative-Breast-Cancer-at-San-Antonio-Breast-Cancer-Symposium [SID1234596620]). The presentations include interim investigational data from H3’s ongoing clinical development program, H3B-6545, a potential first-in-class, orally available Selective ERα Covalent Antagonist (SERCA), in women with ER-positive, HER2-negative breast cancer.

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"At H3, we are developing a pipeline of targeted medicines with the potential to impact the future of cancer treatment," said Ping Zhu, Ph.D., President and Chief Scientific Officer of H3. "Our ongoing clinical study of H3B-6545 is evaluating its potential to address current unmet medical needs in breast cancer either as a single agent or in combination with therapies such as palbociclib. We look forward to showcasing its progress at SABCS 2021."

H3B-6545 PRESENTATIONS

Abstract Number: 976

Title: H3B-6545, a Novel Selective Estrogen Receptor Covalent Antagonist (SERCA), in Estrogen Receptor Positive (ER+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Advanced Breast Cancer – A Phase II Study
Program Number: P1-17-10
Poster Session: 1
Date and Time: Wednesday, December 8, 2021, 7:00am – 8:30am CT
Presenter: Erika P. Hamilton, Sarah Cannon Research Institute, Tennessee Oncology

Abstract Number: 1166
Title: H3B-6545 in Combination with Palbociclib in Women with Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer, Phase 1b Study
Program Number: P1-17-03
Poster Session: 1
Date and Time: Wednesday, December 8, 2021, 7:00am – 8:30am CT
Presenter: Stephen Johnston, Royal Marsden NHS FDN Trust, London, UK

About H3B-6545

Estrogen receptor alpha (ERα) plays an important oncogenic role in the genesis and progression of luminal breast cancers,1 and historically has been a target of endocrine therapies. However, recently, hotspot mutations in ERα have been detected in nearly 30% of endocrine-therapy resistant metastases. Functional studies have shown that these ERα mutations can confer ligand-independent activation of the ERα pathway and can promote partial resistance to existing classes of ER-directed therapies.2,3 H3B- 6545, a first-in-class small molecule selective estrogen receptor covalent antagonist (SERCA) demonstrates activity in tumor models that harbor wild-type or mutant ERα.4 H3B-6545 activity against ERα mutants resistant to standard therapy provides an opportunity to target a currently unmet medical need both as a single agent and in combination with other breast cancer therapies.

This release discusses investigational uses of agents in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational agents will successfully complete clinical development or gain health authority approval.

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]).

"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.

"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]):

"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]).

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."