On May 17, 2023 Clinical stage oncology company Prescient Therapeutics (ASX: PTX) reported that it will present two of its abstracts at an annual conference of the International Society of Cell & Gene Therapy (ISCT) in France later this month (Press release, Prescient Therapeutics, MAY 16, 2023, View Source [SID1234631811]).

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Prescient researchers will showcase new preclinical data on the company’s next-generation immune receptor platform OmniCAR and its cell therapy enhancement platform CellPryme.

Both abstracts will also be published in the next issue of the ISCT’s official journal Cytotherapy.

The ISCT is focused on pre-clinical and translational aspects of cell and gene-based therapeutic developments and aims to advance scientific research into innovative treatments for patients.

The annual conference brings together clinicians, regulators, researchers and industry partners with a shared vision to translate cell and gene technologies into safe and effective therapies.

It attracts more than 2700 experts from 60 countries each year.

On May 16, 2023 Personalis, Inc. (Nasdaq: PSNL), National Cancer Center, and Ono Pharmaceutical Co., Ltd. reported they have entered into a collaborative agreement to examine the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for resectable rectal cancer with mismatch repair deficiency (dMMR) (Press release, Personalis, MAY 16, 2023, View Source [SID1234631799]). As part of the collaboration on the VOLTAGE-2 study, an exploratory analysis will be conducted to evaluate specific biomarkers such as minimal residual disease (MRD) status that may have prognostic or predictive value for patient care.

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Under the agreement, National Cancer Center Hospital East (NCCHE) will recruit patients and conduct the clinical trial, Ono will provide nivolumab, and Personalis will perform MRD and biomarker testing. Biomarker research will be conducted throughout the study, including sample analysis from both tumor lesion tissue and plasma circulating tumor DNA (ctDNA). The Personalis NeXT Personal platform will be used to correlate MRD status with standard of care imaging and drug response data by monitoring variances in ctDNA. Tissue samples will be analyzed by the Personalis ImmunoID NeXT platform to capture tumor molecular profile and tumor microenvironment features to better understand immunotherapy responses.

"We deeply value the opportunity to work with NCCHE and Ono – respected oncology leaders worldwide – to demonstrate the clinical validity of our ultra-sensitive liquid biopsy MRD assay, NeXT Personal, in early-stage rectal cancer patients to better predict drug response and disease recurrence in subsequent interventional trials based on ctDNA status," said Richard Chen, MS, MD, Executive Vice President, R&D and Chief Medical Officer at Personalis. "We believe that data from this study will be another step towards supporting the use of our highly sensitive MRD assay in rectal cancer and other cancer types."

"In our VOLTAGE study, we will include patients with dMMR resectable rectal cancer, who are being treated with nivolumab. Using NeXT Personal, we would like to investigate if an MRD negative result can be the surrogate marker of clinical complete response," said Hideaki Bando, MD, Assistant Chief, Department of Gastroenterology at NCCHE and Principal Investigator and Research Secretariat of the VOLTAGE-2 study. "We also would like to explore the association between immune microenvironment and efficacy of nivolumab using ImmunoID NeXT. These comprehensive assays may enable the selection of cases with high efficacies and will promote the non-operative management in dMMR rectal cancer."

On May 16, 2023 RadioMedix and Orano Med, two clinical stage radiopharmaceutical companies, reported that the last patient has been dosed in the Phase II trial of the targeted alpha emitter therapy, 212Pb-DOTAMTATE (AlphaMedix) (Press release, RadioMedix, MAY 16, 2023, View Source [SID1234631798]). This trial is being conducted to evaluate the safety and effectiveness of AlphaMedix in peptide receptor radionuclide therapy (PRRT) of naive patients with somatostatin receptor-expressing neuroendocrine tumors (NET), regardless of the location of the primary tumor. Top-line data from the trial is expected in mid-2024. Remarkably, based on data already collected, the objective response rate (ORR) endpoint has already been achieved and is more than twice as high as the current standard of care.

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"The completion of the Phase II trial enrolment is a significant milestone in the clinical development of our innovative targeted alpha-emitter radiotherapy, AlphaMedix, and brings us one step closer to having this drug available to patients," said Ebrahim Delpassand, MD, Chairman and Chief Executive Officer of RadioMedix. "Previous studies have shown targeted alpha therapy (TAT) with AlphaMedix is well-tolerated. The preliminary efficacy data seen to date are very promising, particularly achieving the planned ORR endpoint. As the trial progresses, we believe the ORR could improve further. We look forward to reporting data on the study in 2024, which we believe will show that AlphaMedix will provide substantial benefit over currently FDA approved therapies for patients with metastatic or inoperable SSTR-expressing NETs."

This Phase II trial is a multi-center, single arm, non-randomized, open-label basket trial. Forty-one patients with histologically confirmed NETs and positive somatostatin analogue imaging who have not received prior PRRT have been enrolled across four sites in the United States. Treatment consists of four cycles of AlphaMedix at 8-week intervals. The primary endpoint of the trial is safety and effectiveness of AlphaMedix. Efficacy endpoints include objective response rate (ORR) using RECIST v1.1 criteria, progression-free survival (PFS), and overall survival (OS). Additional information about the trial can be found on clinicaltrials.gov: NCT 05153772.

Julien Dodet, President, and Chief Executive Officer of Orano Med, noted: "Completing this Phase II trial enrolment on schedule is a great achievement everyone involved and confirms the strong interest of the medical community for targeted alphatherapies with lead-212. We are convinced that targeted alphatherapies, such as AlphaMedixTM, are the future of radiopharmaceutical therapies, providing an increased cytotoxic potential against cancer cells with limited toxicity to surrounding healthy cells. This reinforces Orano Med’s commitment to make innovative lead-212-based therapies available to the medical community and patients worldwide."

About Targeted Alpha Therapy

Targeted alpha therapy (TAT) relies on a simple concept: combining the ability of biological molecules to target cancer cells with the short-range cell-killing capabilities of alpha-emitting radioisotopes. Alpha decay consists of the emission of a helium nucleus (alpha particle) together with very high linear energy transfer and a range emission of only few cell layers, resulting in irreparable double strand DNA breaks in cells adjacent only to area of alpha emission. This approach results in an increased cytotoxic potential toward cancer cells while limiting toxicity to nearby healthy cells. As a result, alpha emitters are considered as the most powerful payloads to be found for targeted therapies.

About AlphaMedixTM

AlphaMedixTM is a radiolabeled SSTR-targeting therapeutic investigational drug for the treatment of NETs patients. The product consists of SSTR-targeting peptide complex radiolabeled with 212Pb that serves as an in vivo generator of alpha-emitting particles. 212Pb isotope is particularly suitable for SSTR therapy applications based upon its half-life, energy, and decay properties.

About neuroendocrine tumors

Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms that originate from neuroendocrine cells. These neoplasms occur mostly in the gastrointestinal tract and pancreas but can also occur in other tissues including the thymus, lung, and other uncommon sites such as ovaries, heart, and prostate. Most NETs strongly express somatostatin receptors (SSTRs). In the United States, around 12,000 patients are expected to be diagnosed with neuroendocrine tumors, with an average 5-year survival rate of 60% at a metastatic stage.

On May 16, 2023 Boundless Bio, a clinical stage, next-generation precision oncology company developing innovative therapeutics directed against extrachromosomal DNA (ecDNA) for patients with oncogene amplified cancers, reported the closing of a $100 million Series C financing co-led by Leaps by Bayer, the impact investment arm of Bayer AG, and RA Capital Management, with participation from additional new investors, Sectoral Asset Management and Piper Heartland Healthcare Capital (Press release, Boundless Bio, MAY 16, 2023, View Source [SID1234631797]). Boundless Bio will use the financing to advance BBI-355, the first ecDNA-directed therapy (ecDTx), through meaningful clinical readouts from its ongoing Phase 1/2 clinical trial in patients with oncogene-amplified cancers.

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Historically, targeted therapies and immunotherapies have been largely ineffective in treating patients with oncogene amplified cancers. Boundless Bio is the first company wholly dedicated to developing novel therapeutics for patients with oncogene amplified cancers, specifically those enabled by ecDNA. Absent in normal healthy tissue, ecDNA have been observed in 14% of early-stage cancers and up to 40% of metastatic cancers and drive both oncogenesis as well as resistance to current therapeutic approaches. Boundless Bio is leveraging a unique understanding of the vulnerabilities of ecDNA biology with the aim to deliver potentially transformative therapies to the up to 400,000 patients newly diagnosed in the US each year with previously intractable oncogene amplified cancers.

The capital raised will fund initial clinical development of BBI-355, as a single agent and in combination with select therapies, for multiple cancer indications with oncogene amplifications being evaluated in the ongoing Phase 1/2 POTENTIATE clinical trial (NCT05827614). BBI-355 is an orally available, potent, and selective CHK1 inhibitor, which has been shown preclinically to be synthetically lethal to ecDNA-bearing oncogene-amplified cancer cells. The new funds will also support advancement of Boundless Bio’s preclinical pipeline of differentiated ecDTx candidates and its proprietary ecDNA diagnostic clinical trial assay, ECHO (ecDNA Harboring Oncogenes), which is being developed in partnership with SOPHiA GENETICS.

"At Leaps by Bayer, we invest in fundamental breakthroughs in healthcare," said Juergen Eckhardt, M.D., EVP and Head of Leaps by Bayer. "The ability to address oncogene amplified cancers has remained one of the industry’s greatest challenges in the treatment of cancer. We are thrilled to support Boundless Bio, a company whose innovations have the potential to impact the lives of patients who currently have no effective standard of care."

The Series C financing included participation from existing investors Fidelity Management & Research Company LLC, ARCH Venture Partners, Nextech Invest, Wellington Management, Vertex Ventures HC, Redmile Group, Surveyor Capital (a Citadel company), GT Healthcare Capital Partners, Alexandria Venture Investments, PFM Health Sciences, Logos Capital, and City Hill Ventures. In conjunction with the financing, Fabio Pucci, Ph.D., Senior Director of Venture Investments Health at Leaps by Bayer, will join the Boundless Bio Board of Directors.

"We are excited to have Leaps by Bayer join our world-class investor syndicate and to welcome Fabio Pucci to our Board of Directors," said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. "The support from new investors along with the continued commitment of our existing investors emphasizes our momentum and progress in bringing the first ecDNA-directed therapies to patients with oncogene-amplified cancers."

About BBI-355

BBI-355 is a potentially best-in-class checkpoint kinase 1 (CHK1) inhibitor and the first ecDNA-directed therapy (ecDTx) being investigated to treat patients with oncogene amplified cancer. CHK1 is a master regulator of DNA replication stress (RS), which frequently arises from oncogene amplification on ecDNA. Inhibition of CHK1 by BBI-355 is synthetic lethal in cancer cells with oncogene amplification on ecDNA due to their heightened RS. CHK1 was identified and validated as an ecDNA essential target via Boundless Bio’s proprietary Spyglass research platform, leading Boundless Bio to develop BBI-355, an orally available, potent, and selective CHK1 inhibitor. BBI-355 is being evaluated in a first-in-human trial ("POTENTIATE": Precision Oncology Trial Evaluating Novel Therapeutic Interrupting Amplifications Tied to ecDNA) designed to evaluate the safety, maximum tolerated dose, and recommended Phase 2 dose of BBI-355 as a single agent and in combination with select therapies in patients with locally advanced or metastatic solid tumors with oncogene amplifications (NCT05827614).

On May 16, 2023 Arsenal Biosciences, Inc. (ArsenalBio), a clinical stage programmable cell therapy company engineering advanced CAR T-cell therapies for solid tumors, reported that it will present preclinical data on its integrated circuit T cell therapies, AB-1015 and AB-2100, in an oral abstract session and three posters at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) annual meeting in Los Angeles, Calif., May 16-20, 2023 (Press release, ArsenalBio, MAY 16, 2023, View Source [SID1234631796]).

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"We are looking forward to sharing preclinical data that reflects our ongoing commitment to leveraging our unique CRISPR-based approach to the development of new cell therapies for the potential treatment of ovarian cancer and kidney cancer," said Susie Jun, M.D., Ph.D., ArsenalBio’s Chief Medical Officer. "Utilizing our logic gate and shRNA technologies, we demonstrate the potential to enhance tumor specificity and anti-tumor activity of CAR T-cell therapy in solid tumor model systems."

ArsenalBio’s oral abstract session will detail preclinical data on AB-1015, currently in phase 1 clinical development (NCT05617755) for patients with ovarian cancer, that incorporates ArsenalBio’s technologies designed to address the barriers to successful adoptive T cell therapy. The three posters will disclose features and findings on AB-2100, a novel integrated circuit T cell therapeutic candidate engineered for the treatment of kidney cancer. AB-2100 is ArsenalBio’s second pipeline program which is targeting the initiation of a phase 1 trial in 2024.

The following abstracts will be presented as an oral abstract session and three posters during the ASGCT (Free ASGCT Whitepaper) annual meeting.

Abstract 149: Preclinical Development of AB-1015, an Integrated Circuit T Cell Therapy Containing an ALPG/MSLN Logic Gate and FAS/PTPN2 shRNA-miR, for the Treatment of Ovarian Cancer
Session title: Next Generation CAR, TCR, and AAV Technologies for Solid Tumors
Oral Abstract Presentation: Thursday, May 18, 2023, 2:45 – 3:00 p.m., Room 502 AB

CAR T cell activity in solid tumors is limited by off-tumor toxicity, antigen heterogeneity, poor persistence, and functional suppression resulting from the tumor microenvironment (TME). To address these challenges, we have developed AB-1015, an autologous, integrated circuit T (ICT) cell product for the potential treatment of ovarian cancer. The AB-1015 transgene cassette includes two functional modules: an "AND" logic gate designed to limit off-tumor toxicity through dual tumor antigen recognition, and a dual shRNA-miR targeting FAS and PTPN2 to resist TME suppression and to improve ICT cell function. AB-1015 is specific for ALPG/P+MSLN+, in preclinical studies, demonstrates superior potency, expansion, and persistence compared with logic gated T cells alone, and is resistant to ovarian TME suppression. Based on these promising preclinical data, AB-1015 is being studied in a phase I clinical trial (NCT05617755) to assess the safety, pharmacokinetics, immunogenicity, and efficacy for patients with platinum-resistant ovarian cancer.

Abstract 572: A PSMA Neovasculature-Inducible CA9 CAR Resistant to FASL and TGFB Mediated Suppression for the Treatment of ccRCC
Poster Session: Wednesday, May 17, 2023, 12:00 – 2:00 p.m. and 5:30 – 7:00 p.m.

Clinically effective CAR T-cell therapy for solid tumors will require substantial T cell engineering to increase their specificity and potency. We have developed an Integrated Circuit T cell (ICT) that encodes multiple synthetic "modules" to potentially overcome diverse barriers to efficacy in clear cell renal cell carcinoma (ccRCC). ICT cells are generated via CRISPR-mediated, targeted knock-in of a single large transgene into a newly identified safe-harbor locus (GS94). With the goal to improve the therapeutic index of CA9 CAR T cells, we developed an "AND" logic gated ICT cell that requires the presence of two antigens to trigger tumor cell killing, thereby enhancing tumor specificity. Our preclinical findings demonstrate that PSMA x CA9 ICT cells can (i) selectively target antigens that cannot be safely targeted by conventional CARs and (ii) overcome multiple suppressive mechanisms in the tumor microenvironment.

Abstract 1218: High-Throughput Arrayed Screening of Logic-Gated CARs Enables the Selection of Candidates for ccRCC with Optimal Potency and Fidelity Traits
Poster Session: Thursday, May 18, 2023, 12:00 – 2:00 p.m. and 5:30 – 7:00 p.m.

The development of clinically effective CAR T-cell products for solid tumors will require substantial cell engineering to confer sufficient specificity, potency, and persistence. Advances in genome engineering and synthetic biology have provided an increasingly complex set of features that can be introduced into CAR T cells to augment their function. However, combining multiple features may result in unpredictable negative interactions between components. Here, we report the use of high-throughput screening to optimize the design of a highly engineered Integrated Circuit T cell (ICT) product for the treatment of clear cell renal cell carcinoma (ccRCC). We leverage high-throughput screening to generate development-ready candidates for ccRCC with finely tuned desirability criteria in <18 months.

Abstract 1374: Synthetic Pathway Activators (SPAs) Increase Engineered T-Cell Potency and Persistence through Tunable STAT Activation
Poster Session: Friday, May 19, 2023, 12:00 – 2:00 p.m. and 5:30 – 7:00 p.m.

Clinically effective adoptive T cell therapy for the treatment of solid tumors requires robust T cell expansion, persistence, and potency. The Janus-kinase signal transducer and activator of transcription (JAK-STAT) pathway plays a critical role in governing T cell activation and differentiation, making it a potential axis for programming an effective T cell response against solid tumors. To exploit this potential, we synthetically engineered a library of proteins, termed Synthetic Pathway Activators (SPAs), that can constitutively drive STAT signaling at variable levels without external cytokine input. We have developed several classes of SPAs driving different STAT pathways, including what we term Class I SPAs (SPA.I), which primarily drive the STAT3 pathway. The SPA platform allows tuning of T cell biology to engineer T cell therapies with increased antitumor potency and cellular persistence.