On March 20, 2023 CoImmune, Inc., a clinical stage immuno-oncology company working to redefine cancer treatment using best-in-class cellular immunotherapies, reported it has exercised its option to obtain an exclusive license in the CD19-targeted, allogeneic cell therapy field to IL-18 Armored Chimeric Antigen Receptor (CAR) technology under a prior agreement with Memorial Sloan Kettering Cancer Center (MSK) (Press release, CoImmune, MAR 20, 2023, View Source [SID1234629075]). The company plans to couple the technology with allogeneic Cytokine Induced Killer (CIK) cells to launch the clinical development of CMN-008 (Armored CAR-CIK cells) with CD19 as the initial target in B-cell malignancies.

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"We are pleased to obtain an exclusive license in the CD19-targeted, allogeneic cell therapy field to IL-18 Armored CAR technology developed by the renowned researchers at MSK that significantly strengthens our position as a leader in the field of immuno-oncology," said Charles Nicolette, Ph.D., Chief Executive Officer of CoImmune. "As we advance towards the clinical development of a new investigational product with this technology in combination with our proprietary CIK cells, it is important to note that this is not simply another CD19 program. We are preparing to launch the first corporate-sponsored Armored CAR-CIK trial for a B-cell malignancy, and we believe this is an opportunity to dramatically change the therapeutic model to a potential outpatient procedure."

CoImmune designed CMN-008 using a highly potent proprietary CAR-CD19/IL-18 construct co-developed with MSK scientists. The CIK cells are genetically modified using a non-viral bicistronic vector encoding both CAR-CD19 and IL-18 that ensures all CAR+ cells are IL-18+. CMN-008 is manufactured from healthy donor cells requiring minimal tissue match to the patient and is more cost effective to produce than autologous CAR-T therapies.

"Traditional CAR-T therapies require preconditioning lymphodepletion prior to administration which frequently results in infection complications requiring hospitalization," said Renier J. Brentjens, M.D., Ph.D., Deputy Director and Chair of Medicine, Roswell Park Comprehensive Cancer Center, who previously developed the IL-18 Armored CAR technology at MSK. "In animal models evaluating IL-18 Armored CAR technology, there was an increase in durability of responses and anti-tumor activity without requiring lymphodepletion, which could be a real game changer and warrants further evaluation."

CoImmune intends to file an Investigational New Drug (IND) application with the U.S. Food & Drug Administration (FDA) for CMN-008 in mid-2023 followed by the initiation of a Phase 1 clinical trial.

On March 20, 2023 Phanes Therapeutics, Inc. (Phanes), an emerging leader in innovative discovery research and clinical development in oncology, reported that the first patient has been dosed in the phase 1 clinical study (NCT05482893) of PT886, a first-in-class native IgG-like bispecific antibody (bsAb) targeting claudin 18.2 and CD47 for the treatment of gastric, gastroesophageal junction and pancreatic adenocarcinomas (Press release, Phanes Therapeutics, MAR 20, 2023, View Source [SID1234629074]). PT886 was assembled using Phanes’ proprietary bispecific antibody platforms PACbody and SPECpair and was granted orphan drug designation (ODD) for the treatment of pancreatic cancer by the FDA last year.

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PT886 directly kills tumor cells via both the ADCP activity of macrophages and ADCC activity of NK cells, and by targeting both claudin 18.2 and CD47 overexpressed on the surface of tumor cells, it broadens the tumor killing spectrum. Additionally, PT886 is expected to induce the presentation of tumor neoantigens by channeling tumor cells into phagocytotic antigen presenting cells (APCs) and stimulate adaptive immune system by indirectly activating T cell killing of claudin 18.2 low or negative tumor cells through recognition of tumor neoantigens. The anti-CD47 arm of PT886 is highly differentiated and has demonstrated minimum binding to human red blood cells while maintains strong binding activity to CD47 on tumor cells. "PT886 targets a validated tumor associated antigen in claudin 18.2 with enhanced anti-tumor activity and broadened tumor killing spectrum through a best-in-class anti-CD47 arm. It is a product of Phanes’ ingenious innovation in creative design of both novel therapeutic approaches and practical technologies," said Dr. Ming Wang, Founder and CEO of Phanes Therapeutics.

The multi-center Phase I clinical trial of PT886 is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PT886 in patients with locally advanced or metastatic gastric, gastroesophageal junction and pancreatic cancers that have progressed after all available standard therapy or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate. Enrollment in the trial is open to individuals aged 18 years and older who have measurable disease with at least 1 lesion amenable to response assessment per RECIST 1.1 criteria, adequate organ function, and an ECOG performance status of 0 to 1.

For more information on the study please visit ClinicalTrials.gov (NCT05482893).

On March 20, 2023 Oxford Nanopore Technologies plc (Oxford Nanopore) and 4bases, a Switzerland-based company, specialising in kits for sequencing and bioinformatic tools, reported a collaboration to make available 4bases kits with Oxford Nanopore sequencing technology (Press release, Oxford Nanopore, MAR 20, 2023, View Source [SID1234629072]). While appropriate for a broad range of human and cancer genomic analyses, a first target is to enable same day sample-to-answer results for the analysis of the BRCA1 and BRCA2 genes.

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BRCA1 and BRCA2 4bases kits are compatible with Oxford Nanopore’s devices, which start from $1000 for a MinION starter pack, expanding access to accurate, fast and affordable sequencing for any laboratory across Italy and Switzerland.

Internal studies using an extensive set of commercial samples have shown 100% concordance identifying the known genetic variants present within the BRCA1 and BRCA2 genes of these samples. These variants, which include single nucleotide variants and larger changes, are associated with increased cancer risk. . The performance of the kits is equivalent to that of existing gold-standard methods, such as short-read sequencing, MLPA and Sanger sequencing. Research studies using clinical samples are underway in multiple sites.

Sequencing BRCA1 and BRCA2

Mutations in BRCA1 and BRCA2 genes can significantly increase the risk of developing breast and ovarian cancers. Early identification of mutational carriers enables appropriate risk stratifications which can lead to important survival benefits. Additionally, highly effective treatment options such as PARPi (Poly(ADP-ribose) polymerase inhibition) have now been approved for certain cancer patients harbouring BRCA1 and 2 genetic mutations.

In healthcare, routine BRCA1 and BRCA2 genetic testing currently performed for both cancer prevention and treatment are highly centralised and can have a turnaround time ranging from a few weeks to months, depending on the need to batch multiple samples. In certain cases, the long turnaround time can lead to making clinical decisions (like surgical treatment decisions) without the result at hand which can later have strong implications for patients harbouring BRCA mutations.

To address an unmet need for workflows that can rapidly sequence BRCA1 and BRCA2, in matter of hours or day(s), Oxford Nanopore and 4bases will release an end-to-end research workflow using 4bases kits and Oxford Nanopore sequencing technology.

The 4bases kit targets the BRCA1 and BRCAC2 genes through PCR generating short amplicons compatible with Oxford Nanopore’s built-in short fragment mode (SFM) sequencing and, following nanopore library prep and sequencing, the software identifies variants present in these genes to provide a report listing the mutations to the end user.

Gordon Sanghera, CEO, Oxford Nanopore Technologies, commented:

"We are delighted to be working with 4bases on this important work to deliver distributed and accessible sequencing to scientists in Italy and Switzerland. In the first instance, we are excited to see how the combination of 4bases and nanopore sequencing will enable rapid characterisation of the BRCA1 and BRCA2 genes and significantly decrease the time to answer. As our collaboration develops we will see this expanded across the breadth of the 4bases portfolio and this will have a large impact on many research areas."

Fabio Grandi, CEO, 4bases, commented:

"With now over 10 years of activity in the field of next generation sequencing, we at 4bases have witnessed every step of what we can call a revolution, leading to an always faster and more comprehensive acquisition of genomic data to the increasing benefit of clinicians involved with precision medicine. Our solutions are now used on a worldwide basis with the main sequencing systems and are now specifically adapted to the new Oxford Nanopore sequencing technology. After the development of 4eVAR, our new bioinformatics tool, completed last year, this strategic collaboration represents a new and exciting milestone in the 4bases development."

On March 20, 2023 Day one presented its corporate presentation (Presentation, Day One, MAR 20, 2023, View Source [SID1234629071]).

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On March 20, 2023 RayzeBio, Inc., a targeted radiopharmaceutical company developing an innovative pipeline against validated solid tumor targets, reported the completion of enrollment in the Phase 1b portion of the ACTION-1 Phase 1b/3 trial of RYZ101 in patients with SSTR+ gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who have progressed on Lutetium-177 labelled somatostatin analogue therapy (Press release, RayzeBio, MAR 20, 2023, View Source [SID1234629069]). A total of 17 patients were enrolled in a unique dose de-escalation trial. All patients were dosed at the highest recommended dose. The purpose of the Phase 1b clinical trial is to evaluate the safety, tolerability, and pharmacokinetics of RYZ101.

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All 17 patients have crossed the required 8-week dose limiting toxicity (DLT) period and no DLTs were observed
Patients will be administered up to four doses of RYZ101 at 8-week intervals
RayzeBio expects to release safety and preliminary efficacy data from the study during the course of the year at upcoming scientific and medical meetings
"We are thankful to the patients that enrolled in this important study. The interest and enthusiasm is evident based on the over enrollment in Phase 1b. We look forward to reporting safety and preliminary efficacy results from the trial later this year and moving into a Phase 3 registrational study. RYZ101 is backed by a strong scientific rationale and has the potential to play a significant role in the treatment of patients with GEP-NETs," said Susan Moran, M.D., M.S.C.E., Chief Medical Officer of RayzeBio.

About gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors, or GEP-NETs, are rare tumors with an incidence of approximately 18,000 patients annually in the United States. Many GEP-NETs follow an indolent disease course and thus the prevalence of patients with GEP-NETs in the United States is several fold that of the incidence. The prognosis for patients with GEP-NET tumors depends on tumor grade and other histopathologic characteristics. Approximately 80% of GEP-NETs express the somatostatin receptor type 2 (SSTR2). Lutathera is a targeted radiopharmaceutical therapy comprised of a somatostatin analog peptide labeled with the beta-emitting radioisotope Lutetium-177 (Lu177), which received regulatory approval for treatment of adult patients with SSTR+ GEP-NETs in Europe and the United States in 2017 and 2018, respectively. However, most patients who receive Lu177-based somatostatin therapies eventually experience tumor progression and have limited subsequent treatment options.

About RYZ101

RYZ101 is an investigational targeted radiopharmaceutical therapy, designed to deliver a highly potent radioisotope, Actinium-225 (Ac225), to tumors expressing SSTR2. RYZ101 is being evaluated in clinical studies for patients with SSTR+ GEP-NETs who have previously been treated with Lu177-based somatostatin therapies and also in patients with extensive stage small cell lung cancer. Details of the studies can be found at View Source and View Source

Ac225 for the study was provided by multiple sources including the U.S. Department of Energy Isotope Program.