On April 8, 2021 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing novel, targeted and personalized therapies for rare and difficult to treat cancers, reported that the Company will report first quarter 2021 financial results on Thursday, April 22, 2021, after market close (Press release, Cytori Therapeutics, APR 8, 2021, View Source [SID1234577730]). Plus Therapeutics’ management team will then host a conference call and webcast at 5:00 p.m. Eastern Time to discuss the financial results and provide a corporate update.

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A live webcast will be available at ir.plustherapeutics.com/events

Please refer to the information below for conference call dial-in information. Callers should dial in approximately 10 minutes prior to the start of the call.

Conference dial-in: 877-402-3914
International dial-in: 631-865-5294
Conference ID: 3084418
Conference Call Name: Plus Therapeutics First Quarter 2021 Results Conference Call
Following the live call, a replay will be available on the Company’s website under the ‘Investor Relations’ section. The webcast will be available on the Company’s website for 90 days following the live call.

On April 8, 2021 NanoString Technologies, Inc. (NASDAQ: NSTG), a leading provider of life science tools for discovery and translational research, reported the highlights of spatial biology abstracts that will be presented at the 2021 meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper), which will be held virtually from April 10 – 15, 2021 (Press release, NanoString Technologies, APR 8, 2021, View Source [SID1234577746]).

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The GeoMx Digital Spatial Profiler (DSP) enables researchers to characterize tissue morphology to rapidly and quantitatively profile RNA and proteins. To date, NanoString and its collaborators have presented DSP data in dozens of abstracts at major scientific meetings and more than 45 peer-reviewed publications, demonstrating DSP’s utility to address a wide range of biological questions in formalin-fixed paraffin-embedded (FFPE) and frozen tissues. At AACR (Free AACR Whitepaper) 2021, eight abstracts that used GeoMx DSP will be presented during the poster session on Saturday, April 10.

Four of the eight abstracts will be presented by investigators from the GeoMx Breast Cancer Consortium (GBCC), an international network of breast cancer researchers. Their goal is to apply innovative approaches and decipher the spatial context of breast cancer to develop a comprehensive atlas and database of novel biomarkers for the disease.

GBCC Abstracts

Poster 2718: Digital spatial profiling in HER2 positive breast cancer: The road to precision medicine

In this work, the GeoMx DSP was used to profile 71 protein targets and gene expression profiling was done using NanoString’s nCounter PanCancer IO360 assay for primary and metastatic tissues from human epidermal growth factor 2 positive (HER2+) breast cancer (BC) patients. A detailed characterization of carefully chosen immune cold, warm and hot regions of interest (ROI) in the tumor and tumor immune microenvironment of (HER2+) of these samples established that primary tumors had a higher number of immune cells than the metastatic sites. These findings, therefore, suggest that immunotherapy in early-stage BC could be more effective than in advanced BC.

Poster 2701: Molecular profiling to assess the immune response to neoadjuvant SABR in early breast cancer

NanoString’s Human PanCancer immune profiling panel was used to assess the impact of localized radiotherapy to elicit an immune response in primary breast carcinomas before lumpectomy. They analyzed 25 patient samples for low-risk primary breast carcinomas from the SIGNAL 2.0 clinical trial using the GeoMx DSP platform, pre, and post stereotactic body radiation therapy (SBRT). Significant differences were found in the gene expression patterns in the immune microenvironment gene expression patterns and cellular composition after radiotherapy, demonstrating that SBRT treatment indeed evokes an immune response, increasing the innate immune response.

Poster 2698: Spatial gene expression profiling in breast cancer

Transcriptome profiling was performed for a cohort of breast cancer lumpectomies using the Cancer Transcriptomic Atlas (CTA) assay on the GeoMx DSP platform. Analysis of 60 patient samples revealed region-specific heterogeneity in unifocal and multifocal cancer tumors. This study demonstrates and establishes the importance of interactions between immune and tumor cells in the tumor microenvironment and the need to develop a strategy to stratify patients to available targeted therapies.

Poster 2726: Characterization of immune microenvironment and heterogeneity in breast cancer subtypes

In this work, the immune microenvironment of Luminal A, Luminal B, Basal, and HER2 tumor subtypes in a cohort of early breast cancer patients was studied using protein biomarkers. The markers were delineated in a spatial context using the GeoMx DSP. Characterization of the immune microenvironment subtypes provided evidence for potential clinical use for GeoMx DSP in diagnosing and better stratifying breast cancer patients based on spatial heterogeneity in tumor and tumor microenvironment.

Other spatial abstracts

Poster 339: Resistance to trastuzumab is associated with alpha-smooth muscle actin expression in the stroma of patients with HER2+ breast cancer

GeoMx DSP was used to identify biomarkers for resistance to trastuzumab in HER2+ breast cancer. Fifty-eight protein targets were analyzed in three different regions of interest (tumor [PanCK+], leukocyte [CD45+/CD68-], and macrophage [CD68+]) in a cohort of 151 breast cancer patients that received trastuzumab. The study uncovered a-SMA as a potential biomarker to augment the predictive value of the current standard of care HER2 assay and justifies its further validation in the light of the many new HER2 targeted therapies.

Poster 705: SARS-CoV-2 infection of the human heart governs intracardiac innate immune response

Spatial profiling of human post-mortem cardiac samples of SARS-CoV-2 infected myocardium was carried out using NanoString’s Whole Transcriptome Analysis (1,864 genes) panel, along with a matching proteome panel on the GeoMx digital spatial profiler. The purpose of their investigation was to elucidate the molecular mechanisms underlying cardiac toxicity, a severe cause of morbidity and mortality in patients on DOX therapy. The study showed interesting gender-specific differential gene expression patterns in the myocardium between SARS-CoV-2 infected and control regions of interest. Signatures of enhanced innate and acquired immune signaling, apoptosis and autophagy, chromatin remodeling, reduced DNA repair, and reduced oxidoreductase activity were all observed in regions of infection. Additionally, DOX-induced increase in the expression of TMPSS2 and cathepsins A, B, and F, clearly indicated enhanced SARS-CoV-2 susceptibility in the myocardium, thus placing cancer patients on DOX therapy at increased risk of cardiac damage.

Poster 2731: Cell-type deconvolution of African American breast tumors reveals spatial heterogeneity of the immune microenvironment

Researchers at the University of Chicago carried out spatial gene expression analysis within localized segments of TNBC tumors from a cohort of self-reported African American patients in the Chicago Multi-Ethnic Breast Cancer Study (ChiMEC). Regions of interest for spatial characterization of tumor and tumor microenvironment using the GeoMx DSP Cancer Transcriptome Atlas assay were manually selected based on the specific morphologies. The 1,825 genes interrogated in the CTA assay provided a granular understanding of the immune landscape’s heterogeneity within tumors.

Poster 2771: Comprehensive analysis of immuno oncology markers in the tumor microenvironment of solid tumor samples using GeoMxTM digital spatial profiler (DSP) and MultiOmyxTM hyperplexed immunofluorescence (IF)

This study describes a multi-faceted highly multiplexed tissue analysis of critical Immuno oncology (IO) protein markers in a pan-cancer cohort of up to 35 FFPE samples originating from breast, head, and neck, prostate, non-small cell lung cancer (NSCLC), endometrial and colorectal indications using NanoString human IO panel on GeoMx DSP in combination with a complementary MultiOmyx Hyperplexed Immunofluorescence (IF) assay. The spatial and quantitative data outputs from DSP nCounter system and cell classification information from the MultiOmyx assay provided the researchers an ability not only to characterize the immunophenotypes but also to visualize the spatial distribution of tumor-infiltrating immune cells at a single-cell resolution within the TME.

Spotlight Theaters at AACR (Free AACR Whitepaper)

NanoString will be hosting two spotlight theaters during AACR (Free AACR Whitepaper) 2021. The first spotlight theater presentation is April 11 from 1:00-2:00 pm EDT, featuring Joseph Beechem, Ph.D., senior vice president of R&D and chief scientific officer for NanoString, with an overview of the latest developments in spatial biology, True spatial genomics: Measuring the transcriptome in regions, cell and sub-cellular compartments. Dr. Beechem will explain spatial technologies’ evolution and their applications from multi-cell to single-cell and subcellular resolution, using the GeoMx DSP and the company’s Spatial Molecular Imager.

The second NanoString spotlight theater is Tuesday, April 13, from 11:00-12:00 pm EDT, and is entitled: New Approaches for Cellular Therapies: Technology Symposium Featuring the GeoMx DSP and nCounter CAR-T Characterization. This panel will include three speakers, Dr. Ryan Golden, Resident Physician in Clinical Pathology, Carl June Lab, University of Pennsylvania; Dr. Marco Ruella, Assistant Professor of Medicine, University of Pennsylvania; and Ghamdan Al-Eryani, Ph.D. Student, Tumor Progression Group from the Garvan Institute. Each speaker will discuss new approaches to CAR-T characterization using the spatially-resolved and bulk RNA analysis, from understanding resistance in CART immunotherapy in lymphoma to TCR diversity in melanoma.

NanoString has launched a Technology Access Program (TAP) for the recently announced single and subcellular Spatial Molecular Imager to complement the existing TAP program for GeoMx. Under the program, customers can submit tissue samples to NanoString for analysis using the spatial profiling platforms and receive a complete data package. Researchers interested in participating in NanoString’s Technology Access Program should contact the company at [email protected].

On April 8, 2021 GT Biopharma, Inc. (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary NK cell engager (TriKE) protein biologic technology platform, reported the enrollment of Patient 10 in its GTB-3550 TriKE first-in-human Phase I/II clinical trial for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML) (Press release, GT Biopharma, APR 8, 2021, View Source [SID1234577763]). Patient 10 will be dosed at 100mcg/kg/day.

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Highlights from the first nine patients treated with GTB-3550 TriKE include:

Up to 63.7% Reduction in Bone Marrow Blast Levels
Restores Patient’s Endogenous NK Cell Function, Proliferation and Immune Surveillance
No Progenitor-derived or Autologous/Allogenic Cell Therapy Required
No Cytokine Release Syndrome Observed
3 out of the Last 5 Patients Treated (25mcg/kg/day to 100mcg/kg/day) Respond
"We are pleased with the continued clinical performance of our lead TriKE product candidate, and in reaching this important patient enrollment milestone," said Anthony J. Cataldo, GT Biopharma’s Chairman and Chief Executive Officer. "The data from the first nine patients treated with GTB-3550 indicates significant bone marrow blast level reductions in AML and MDS patients without the need for expensive progenitor-derived or autologous/allogenic cell therapies."

About High-Risk Myelodysplastic Syndromes
MDS is a rare form of bone marrow-related cancer caused by irregular blood cell production within the bone marrow. As a result of this irregular production, MDS patients do not have sufficient normal red blood cells, white blood cells and/or platelets in circulation. High-risk MDS is associated with poor prognosis, diminished quality of life, and a higher chance of transformation to acute myeloid leukemia. Approximately 40% of patients with High-Risk MDS transform to AML, another aggressive cancer with poor outcomes.

About Acute Myeloid Leukemia
Acute myeloid leukemia is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells, or platelets. According to the National Cancer Institute (NCI), the five-year survival rate is about 35% in people under 60 years old, and 10% in people over 60 years old. Older people whose health is too poor for intensive chemotherapy have a typical survival of five to ten months. AML accounts for roughly 1.8% of cancer deaths in the United States.

About GTB-3550 TriKE
GTB-3550 is the Company’s first TriKE product candidate being initially developed for the treatment of AML and MDS, and other CD33+ hematologic cancers. GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of Interleukin 15 (IL-15). The natural killer (NK) cell-stimulating cytokine human IL-15 portion of the molecule provides a self-sustaining signal that activates NK cells and enhances their ability to kill. We intend to study GTB-3550 in CD33 positive leukemias such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and other CD33+ hematopoietic malignancies.

About GTB-3550 TriKE Clinical Trial
Patients with CD33+ malignancies (primary induction failure or relapsed AML with failure of one reinduction attempt or high-risk MDS progressed on two lines of therapy) age 18 and older are eligible (NCT03214666). The primary endpoint is to identify the maximum tolerated dose (MTD) of GTB-3550 TriKE. Correlative objectives include the number, phenotype, activation status and function of NK cells and T cells.

On April 8, 2021 The University of Texas MD Anderson Cancer Center and TriSalus Life Sciences, an emerging immuno-oncology company committed to transforming outcomes for patients with liver and pancreatic tumors, reported a strategic research collaboration to evaluate the treatment of tumors of the pancreas and liver by integrating interventional delivery of SD-101, an investigational toll-like receptor 9 (TLR9) agonist, in combination with checkpoint inhibition immunotherapy (Press release, TriSalus Life Sciences, APR 8, 2021, View Source [SID1234577715]).

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Under the agreement, MD Anderson and TriSalus will collaborate on studies evaluating the administration of investigational SD-101 intravascularly via TriSalus’ Food and Drug Administration (FDA) cleared, proprietary Pressure-Enabled Drug Delivery (PEDD) technology across a range of liver and pancreatic solid tumors. The initial study will focus on liver metastases from uveal melanoma, followed by studies focused on metastatic disease from pancreatic ductal adenocarcinoma and colorectal cancer. Programs for hepatocellular carcinoma and locally advanced pancreatic ductal adenocarcinoma also are under development. TriSalus will provide funding and technology for the studies.

"We’re pleased to collaborate with MD Anderson in pursuit of our collective goal to improve outcomes for patients with tumors of the liver and pancreas. The goal of these studies is to augment the potential of existing therapies through novel drug delivery technology and to investigate the strategic modulation of immune microenvironments with investigational candidate SD-101," said Steven Katz, M.D., Chief Medical Officer, TriSalus Life Sciences. "Collaborations such as this are an integral part of our development strategy to evaluate treatments to help overcome the challenges inherent to solid tumors and enable a broader population of cancer patients to benefit from immunotherapy."

SD-101 has been evaluated in phase 2 studies in advanced cutaneous melanoma and head and neck cancer.1,2 Early data suggests SD-101 augmented responsiveness to checkpoint inhibitors through stimulation of innate immune cells, along with favorable programming of the T cell population.3 The planned studies under the research collaboration are intended to deliver SD-101 deep into the vasculature of solid tumors using PEDD, a technique not previously possible using standard delivery approaches.4

Solid tumors continue to represent one of the single biggest hurdles to successful cancer treatment.5 High levels of pressure inside solid tumors prevent the delivery of oncology therapeutics, with less than 1% of therapy penetrating solid tumors in some circumstances.6,7 TriSalus developed PEDD to deliver immuno-oncology therapeutics directly into the vasculature of solid tumors.

"Tumors in the pancreas and liver are notoriously difficult to treat effectively, and these patients need new therapeutic options. Our collaboration with TriSalus provides a unique opportunity to evaluate immunotherapy in combination with a novel delivery approach," said Sapna Patel, M.D., associate professor of Melanoma Medical Oncology at MD Anderson. "We look forward to our work together to advance new treatments aimed at improving clinical outcomes and the lives of our patients."

On April 8, 2021 IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (NASDAQ: IPA) (TSX VENTURE: IPA) a leader in full-service, therapeutic antibody discovery and development, reported that its subsidiary Talem Therapeutics LLC ("Talem") has advanced development of a candidate panel of vetted, novel, therapeutic antibodies, collectively referred to as TATX-112, against an undisclosed target, into formal lead candidate characterization (Press release, ImmunoPrecise Antibodies, APR 8, 2021, View Source [SID1234577731]).

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It is well documented that certain genes, when mutated and expressed in different tissues and organs, may play a role in more than one disease.

Oncology

The target is a protein receptor that is overexpressed in a variety of types of deadly cancers. In solid tumors, stimulation of the target by its ligand is described to result in activation of intracellular signaling pathways that promote cancer cell growth, survival, invasiveness, metastatic behavior, and suppress chemotherapeutic sensitivity of the tumor cells. Therefore, interference with the target signaling is anticipated to be an attractive approach to induce tumor suppression, or halting tumor cell growth. As current therapies focusing on inhibiting intracellular target signaling consist primarily of non-target selective small molecule inhibitors, they may be high risk for unintentionally causing undesirable side-effects to the patient by functionally blocking related receptor proteins, which are more widely expressed in the human body, in parallel. In contrast, Talem has developed the TATX-112 antibodies with the goal of specifically blocking the interaction between the target and its ligand, e.g. functionally interfering with the target’s biology, which is expected to significantly improve specificity of such tumor therapy due to its relatively higher expression levels in tumors compared to normal tissue. That higher specificity is expected to increase the therapeutic window by lowering the potential risk of side effects and positively impacting treatment efficacy. Additionally, the target’s expression profile makes this membrane protein a promising candidate for antibody-drug conjugate-based therapies.

Neurodegenerative Diseases

In addition to its role in oncology, the target plays a vital role in the nervous system by enhancing neuronal development, survival, protection, and function. Alzheimer’s and other neurodegenerative diseases are associated with reduced expression levels of the target and impaired receptor signaling. Stimulating intracellular target signaling using agonistic antibodies is an appealing therapeutic approach to suppress disease progression with an expectedly higher safety profile than less-selective small molecules. Such therapeutic strategy requires blood-brain-barrier passage which can be facilitated by a bi- or multi-specific antibody format, including an antibody fragment that induces transport over the blood-brain-barrier upon binding.

Talem’s Pipeline

As the different clinical application options for TATX-112 antibodies require a functionally diversified set of lead candidates and antibody format flexibility, Talem relied on two of IPA’s proprietary target-enrichment antibody discovery platforms, B cell Select and DeepDisplay. Following selection of both target-reactive B cells from target immunized chicken and human scFvs from IPA’s in-house phage libraries, 50 sequence-unique antibodies of particular interest were prioritized for more in-depth characterization to bin antibodies for further (indication-specific) clinical development.

In addition to TATX-112, Talem is continuing development efforts of its other potential products leveraging its pipeline of highly differentiated therapeutic antibody programs for the potential treatment of various disease areas, including heart disease, inflammation, infectious diseases and cancer. The Company’s most advanced development program, TATX-03 ("anti-SARS PolyTope"), is a fully human, synergistic, antibody cocktail containing potently neutralizing antibodies against non-overlapping epitopes on SARS-CoV-2.

"Generating a diversified anti-target antibody panel during the discovery phase is key to a successful therapeutic lead campaign, in particular for programs that are aimed at obtaining antibodies with different modes of action," stated ImmunoPrecise President and CEO, Dr. Jennifer Bath. Leveraging our robust target-enrichment antibody discovery technologies, B cell Select and DeepDisplay, we discovered a highly sequence diverse pool of anti-target antibodies, which allows proper down-selection of the best-performing lead candidates for further development, thereby increasing the chance of successful clinical application."

About B cell Select

IPA’s B cell Select platform enables the interrogation of a greater diversity of an antibody repertoire. By interrogating isolated B cells, IPA can analyze full organism repertoires with very little manipulation. This proprietary platform is species independent allowing for the generation of antibodies from samples not possible using other methods. B cell Select has the potential to develop antibodies from any species (including humans) as well as from any tissue. As the platform explores the entire antibody repertoire, it provides the opportunity to develop antibodies for anything that is possible in an animal’s immune repertoire including any protein class, complex therapeutic targets, post-translational modifications, and small molecules.

The B cell Select platform enables the interrogation of 10 million blood cells to generate native monoclonal antibodies from immunized animals that specifically target an antigen. The B cell Select process takes place early in the antibody development process allowing for the rapid selection of top candidates, drastically increasing the success rate of antibody discovery. The platform also harnesses the power of the immune system to generate natural pairing of the antibodies produced by selected B cells.

About DeepDisplay

IPA’s DeepDisplay is a phage display approach based on building custom immune libraries from multiple species, including transgenic animals, or the selection of antigen-specific recombinant antibody fragments from our proprietary human or llama phage libraries. Our libraries have been made from human patient and naïve (scFv) repertoires, as well as from naïve llama (VHH) repertoires. Custom immune libraries are prepared from blood, spleen, lymph nodes, and bone marrow of immunized animals or humans and capture the entire immune repertoire for panning, rescue, and identification of unique antibodies with pre-specified characteristics.