On April 8, 2022 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat solid tumors in the advanced cancer setting and for the clearance of human papillomavirus and related pre-cancerous cervical lesions, reported the presentation of interim data from a first-in-human, Phase 1 study evaluating PRTX007, a novel, small molecule toll-like receptor 7 (TLR7)-specific agonist, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans (Press release, Primmune Therapeutics, APR 8, 2022, View Source [SID1234611760]). The study is a single-center, prospective, randomized, double-blind, placebo-controlled study with 9 single-ascending dose (SAD) cohorts and 4 multiple-ascending dose (MAD) cohorts where PRTX007 is administered orally to adult healthy volunteers. In addition to assessing the safety, tolerability and pharmacokinetics of PRTX007, the study is designed to evaluate pharmacodynamic responses relevant to dose selection for patients with cancer.

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"These data from our ongoing first-in-human trial indicate that Primmune’s lead candidate, PRTX007, is well-tolerated in healthy volunteers and activates the desired components of innate and downstream adaptive immune responses while avoiding induction of proinflammatory cytokines," said James Appleman, Ph.D., Co-Founder and Chief Scientific Officer at Primmune Therapeutics. "We look forward to the clinical advancement of PRTX007 for the treatment of solid tumors in combination with checkpoint inhibitors and as a monotherapy for the treatment of human papillomavirus-driven pre-cancerous cervical lesions and the underlying infection."

Data show that PRTX007 was well-tolerated and expressed a favorable safety profile in the analyzed patient cohorts, with most adverse events (AEs) considered incidental and no instances of moderate, severe or serious AEs. In addition, every other day (QOD) dosing demonstrated stable systemic immune induction without evidence of counter-regulation. Both the clinical characteristics and unique pattern of immune induction by PRTX007 support its use in combination with immune checkpoint inhibitors.

Presentation Title: PRTX007, an Optimized TLR7 Agonist for Systemic Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)s: Interim Analysis of Phase I Study in Healthy Volunteers
Presenting Author: Curtis Scribner, M.D., Chief Medical Officer, Primmune
Abstract Number: 8165
Poster Number: CT189
Poster Board Number: 14
Poster Session: Phase I Clinical Trials 2 Session
Session Date and Time: Tuesday, April 12, 9 a.m. to 12:30 p.m. CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 33

Additional highlights from the poster presentation include:

Most AEs were incidental and not dose related. The most common drug-related AE was headache, seen across both treated and placebo groups independent of dose.
At the interim analysis, PRTX007 demonstrated a favorable safety profile when administered orally to all 9 SAD and 3 MAD cohorts tested.
PRTX007 demonstrated induction of interferon-stimulated genes (ISGs) without significant increases in circulating interferons (IFNs). There was no increase in expression or circulating levels of proinflammatory cytokines (e.g., TNFα, IL-6, IL-1β).
About PRTX007

PRTX007, Primmune’s lead clinical development candidate, is designed to provide well-tolerated, controlled, long-term stimulation of the innate immune response while also potentiating long-term effective innate and adaptive immune responses. PRTX007 uniquely activates plasmacytoid dendritic cells (pDCs), leading to a systemic immune poly-IFN response without stimulating production of NF-κB-driven proinflammatory factors like IL-6, TNFα or IL-1β. Furthermore, activated pDCs directly deliver interferons to target cells by paracrine transfer. This is functionally equivalent to administering a cocktail of all Type I/III IFN while avoiding the associated side effects and adverse events. PRTX007 is being rapidly advanced towards clinical trials for solid tumors in the advanced cancer setting and for clearing human papillomavirus-driven pre-cancerous cervical lesions.

On April 8, 2022 AbCellera (Nasdaq: ABCL), a technology company focused on next-generation antibody discovery, reported the release of data on its new T cell engager platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting (Press release, AbCellera, APR 8, 2022, View Source [SID1234611759]). AbCellera’s poster presentation describes the discovery, characterization, and validation of a diverse panel of CD3-binding antibodies that can be used to develop bispecific CD3 T cell engagers for new cancer treatments.

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"T cell engagers are widely recognized for their tremendous potential as precision oncology therapeutics. However, a limited pool of available CD3-binding antibodies and technological challenges in engineering bispecifics have hindered development, leading to many first-generation molecules with poor efficacy or safety," said Bo Barnhart, Ph.D., VP, Translational Research at AbCellera. "Our discovery engine has allowed us to build a panel of hundreds of diverse and fully human CD3-binding antibodies. Combined with our OrthoMabTM bispecific platform, this enables rapid screening of many combinations of CD3- and tumor antigen-binding antibodies to find pairs with optimal biological function and good developability."

CD3 T cell engagers, which bind to T cells and cancer cells simultaneously, are able to redirect T cells to tumor cells, regardless of T cell specificity. Two different parental antibodies, a CD3-targeting antibody that fine-tunes T cell activation and a tumor-targeting antibody with high specificity for cancer cells, are needed to create an optimal bispecific T cell engager. Highly diverse panels of developable and functionally validated parental antibodies increase the probability of finding effective and manufacturable CD3 T cell engagers and reduce the need for downstream engineering to eliminate liabilities.

AbCellera used its technology stack to discover a panel of CD3-binding antibodies from humanized mice. Bioinformatic analysis revealed high sequence diversity, including somatic hypermutation, a range of CDR3 lengths, and diverse V gene usage. The panel was also found to be functionally diverse, including a broad range of CD3 affinities and T cell activation potencies. Biophysical characterization demonstrated that AbCellera’s CD3-binding antibodies have favorable developability properties, which may reduce the time and technical risks of downstream protein engineering, including low mean hydrophobicity, self-association, and polyspecificity.

AbCellera used its clinically validated bispecifics platform, OrthoMabTM, to pair the CD3-binding antibodies with a single EGFR-binding arm to validate the panel in bispecific formats. The resulting bispecific antibodies activated T cells with a range of potencies and led to T cell-mediated tumor cell killing of EGFR-expressing cell lines.

"The data from our T cell engager program, which we initiated in late 2021, show the power and speed of AbCellera’s robust platform," said Neil Berkley, AbCellera’s Chief Business Officer. "Our panel of CD3-binding antibodies offers partners the ability to unlock this promising modality and accelerate their oncology programs by streamlining the development of new cancer treatments."

Details on AbCellera’s presentation at AACR (Free AACR Whitepaper) are as follows:

Title: Redirecting T cells to tumor targets with functionally diverse CD3-binding antibodies
Presenter: Bryan (Bo) C. Barnhart, Ph.D., VP Translational Research, AbCellera
Session: Antibodies and Immune Therapies — Abstract #312
Date and time: Sunday, April 10 at 1:30-5:00 PM CDT

The poster is available for viewing here.

On April 8, 2022 Immunomic Therapeutics, Inc., ("ITI"), a privately-held clinical-stage biotechnology company pioneering the study of LAMP-mediated nucleic acid-based immunotherapy, reported that the data from two posters are being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 held in New Orleans, Louisiana, from April 8-13 (Press release, Immunomic Therapeutics, APR 8, 2022, View Source [SID1234611758]). These posters to be presented at the AACR (Free AACR Whitepaper) Meeting focus on the investigational nucleic acid platform, UNITE (UNiversal Intracellular Targeted Expression) for two vaccines, ITI-3000 for Merkel cell carcinoma (targeting the large T antigen of the Merkel cell polyomavirus) and Her2/Neu-LAMP DNA vaccine, both of which fuse a tumor associated antigen with lysosomal associated membrane protein 1 (LAMP-1). This proprietary lysosomal targeting technology results in enhanced antigen presentation and a balanced T cell response.

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The posters are accessible on the "Posters" section of Immunomic Therapeutics’ website at: View Source

Highlights from the presentations are as follows:

Poster Number: 10

Title: "LAMP1 targeting of the large T antigen of Merkel cell polyomavirus elicits potent CD4+ T cell responses, tumor inhibition, and provides rationale for first-in-human trial"

Authors: Claire Buchta Rosean, PhD1; David M. Koelle, MD2; Paul Nghiem, MD, PhD3, Mohan Karkada, PhD1, Teri Heiland, PhD1

1Immunomic Therapeutics Inc., Rockville, MD, USA 2Department of Medicine/Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA 3Department of Medicine, Department of Dermatology, University of Washington, Seattle, WA, USA

This presentation reports results of pre-clinical mouse studies of a cancer vaccine that promotes potent, antigen-specific CD4 T cell responses to MCPγV-LT. The majority of Merkel cell carcinomas (MCC), a rare and highly aggressive type of neuroendocrine skin cancer, are associated with Merkel cell polyomavirus (MCPyV) infection. MCPyV integrates into the host genome, resulting in expression of a truncated form of the viral large T antigen (LT) in infected cells, and makes LT an attractive target for therapeutic cancer vaccines.
To activate antigen-specific CD4 T cells in vivo, the investigators utilized the nucleic acid vaccine platform, UNITE (UNiversal Intracellular Targeted Expression), which fuses a tumor-associated antigen with lysosomal-associated membrane protein 1 (LAMP1). LTS220A, encoding a mutated form of MCPγV-LT that diminishes its pro-oncogenic properties, was introduced into the UNITE platform. Mice were vaccinated with 40µg of ITI-3000 or control vector via intradermal injection and electroporation. A B16F10 melanoma line stably transduced to express LTS220A (B16-LT) was injected subcutaneously in the right flank.
Vaccination with LTS220A-UNITE (ITI-3000) induced antigen-specific CD4 Th1 cells that was associated with delayed tumor growth and enhanced survival in treated mice in both the prophylactic and therapeutic settings. This effect was dependent on the CD4 T cells ability to produce IFNγ (interferon gamma), suggesting the potential mechanism of action of ITI-3000. In addition, ITI-3000 induced changes in the tumor microenvironment, including increased numbers of CD4 and CD8 T cells, reduced frequency of myeloid cells, and enhanced pro-inflammatory cytokine production.
Poster Number: 3

Title: "Harnessing soluble CD40L to enhance anti-tumor efficacy of Her2-LAMP DNA vaccine using UNITE platform"

Authors: Wei Shen1, Renhuan Xu2, Yun-Ting Kao1, Mohan Karkada1, and Teri Heiland1

1Immunomic Therapeutics, 15010 Broschart Road, Rockville, MD 20850 2ARV-Tech, Rockville, MD 20852

This presentation reports results of preclinical mouse studies on a HER2/Neu-LAMP DNA vaccine that included a bicistronic DNA construct in which both the tumor antigen (HER2) fused with LAMP-1 (lysosomal- associated membrane protein 1) and sCD40L were expressed separately. CD40 ligand (CD40L; CD154) is a transmembrane protein expressed on the surface of activated T cells, particularly on CD4 T cells, which stimulates CD40-dependent activation of antigen-presenting cells (APCs), resulting in enhancement of T cell and antibody responses.
To elicit cellular and humoral responses, the investigators employed the proprietary UNITE (UNiversal Intracellular Targeted Expression)-VAX platform, which utilizes a plasmid DNA expressing TAAs and LAMP to deliver TAAs to the MHC II compartment, thus potentially enhancing both antibody generation and CD4+ T cell response. Mice were immunized intradermally with 20µg of control vector, HER2-LAMP, or bicistronic-HER2-LAMP-sCD40L.
Vaccination with HER2-LAMP-sCD40L was associated with the detection of soluble forms of CD40L in the supernatant of HER2-LAMP-sCD40L transfected 293T cells: this soluble CD40L may function to enhance vaccine immunogenicity. The HER2-LAMP-sCD40L DNA vaccine elicited a robust HER2- specific cellular and humoral response; of note, CD4 T cells were elevated as compared with CD8 T cells, suggesting that sCD40L preferentially acts on CD4 T cells in vivo. The HER2-LAMP-sCD40L DNA vaccine exhibited significant antitumor effect in a murine breast tumor model.
"Based on these preclinical findings, we are planning a first-in-human Phase 1 open-label study to evaluate the safety, tolerability, and immunogenicity of ITI-3000 in Merkel cell carcinoma patients," stated Dr. William Hearl, Chief Executive Officer of Immunomic Therapeutics. "This study will be our second clinical study utilizing our proprietary nucleic acid vaccine platform UNITE and underscores the potential for our platform to design and introduce novel cancer vaccines for hard-to-treat cancers."

"We are highly encouraged by the data from the preclinical development for Her2-LAMP-sCD40L vaccine," stated Teri Heiland, PhD, Chief Scientific Officer of Immunomic Therapeutics. "The prolonged survival noted in the murine model suggests that this novel bicistronic vaccine may be an effective strategy to promote anti-tumor efficacy in vivo for multiple HER2-expressing cancer types."

About UNITE

ITI’s investigational UNITE platform, UNiversal Intracellular Targeted Expression, leverages the ability to engineer chimeric proteins, directing antigen presenting cells to present antigens to the immune system through a targeted pathway and driving a robust immune response. UNITE vaccines are distinct in that they combine two components: nucleic acid constructs that encode a specific antigen and an endogenous Lysosomal Associated Membrane Protein (LAMP-1) sequence. The UNITE platform harnesses LAMP-1 as a means of presenting the vaccine target to the immune system, resulting in antibody production, inflammatory cytokine release, and establishing critical immunological memory, something that other vaccine approaches commonly lack. This approach could put UNITE technology at the crossroads of immunotherapies in multiple indications, including cancer, human allergy, animal health, and infectious disease. Preclinical data is currently being developed to explore whether LAMP-1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and used to create immune responses in tumor types that otherwise do not provoke an immune response.

On April 8, 2022 Asana BioSciences, LLC, a clinical stage biopharmaceutical company, reported that the first patient has been dosed in a Phase 1 trial for ASN004, an antibody drug conjugate (ADC) targeting the 5T4 oncofetal antigen (trophoblast glycoprotein), that is expressed in a wide range of malignant tumors but shows very limited expression in normal tissues (Press release, Asana BioSciences, APR 8, 2022, View Source [SID1234611757]). Higher 5T4 expression is associated with worse clinical outcome in non-small cell lung, head and neck, gastric, pancreatic, colorectal, and ovarian cancers.

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ASN004 incorporates a novel single-chain Fv-Fc antibody linked to a clinically validated Auristatin F hydroxypropylamide cytotoxic payload, and drug to antibody ratio (DAR) of approximately 10-12. In preclinical cancer models, a single dose of ASN004 achieved complete and durable tumor regression leading to tumor-free survivors.

"5T4 is an ideal antigen target for payload delivery to tumor with high internalization rate dynamics combined with the high DAR and represents a clear opportunity for precision guided therapy as needed" said Dr. Anthony Tolcher, Director of Clinical Research, Next Oncology, San Antonio, Texas and the Principal Investigator of the Phase 1, multicenter, dose-finding study, designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of ASN004, in patients with advanced solid tumors in the US (NCT04410224).

"We are delighted to initiate the clinical development of ASN004. The broad tumor expression profile of 5T4 qualifies it as a promising target for cancer therapies, with potential to be the best-in-class ADC," said Sandeep Gupta, PhD, Founder, President and Chief Executive Officer at Asana BioSciences. "ASN004 is the 6th novel program that Asana has successfully brought into the clinic, affirming our mission to provide new and better treatment options to patients," added Dr. Gupta.

On April 8, 2022 NanoString Technologies, Inc. (NASDAQ: NSTG), a leading provider of life science tools for discovery and translational research, reported the highlights of over 125 studies enabled by NanoString platforms that will be presented at the 2022 meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper), which will be held April 8-13, 2022 (Press release, NanoString Technologies, APR 8, 2022, View Source [SID1234611756]).

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At AACR (Free AACR Whitepaper) 2022, over 110 posters and 15 oral presentations will showcase unique biological insights generated using NanoString Technologies’ platforms. This is the largest number of AACR (Free AACR Whitepaper) abstracts in a single year for NanoString and demonstrates the increasing adoption of spatial biology in cancer research. These abstracts include at least 36 studies exploring spatial biology using the CosMx Spatial Molecular Imager (SMI) and GeoMx Digital Spatial Profiler (DSP), and 59 studies exploring gene expression using the nCounter Analysis System.

"NanoString customers continue to make tremendous contributions to our understanding of cancer and the development of cures," said Brad Gray, president and CEO of NanoString. "We are particularly excited to highlight research studies that leverage our latest product offerings in spatial biology. These include simultaneous detection of RNA and protein on a single slide using GeoMx DSP and 100-plex protein imaging using the CosMx SMI."

Several studies and presentations that feature the use of NanoString’s spatial biology platforms are highlighted below.

Spotlight Theater, April 12, 10:00-11:00 am CST

NanoString will host a spotlight theater during AACR (Free AACR Whitepaper) on April 12 from 10:00-11:00 am CST, featuring Joseph Beechem, Ph.D., senior vice president of R&D and chief scientific officer for NanoString, presenting "Spatial Whole Transcriptome Profiling and Single Cell High-Plex Imaging: Quantum Leaps Forward in Studying Cancer." Arutha Kulasinghe, Ph.D., National Health and Medical Research Council (NHMRC) Research Fellow, Queensland University of Technology, will present "Spatial genomics in immunotherapy…and COVID-19." And Hargita Kaplan, director of Translational Medicine, Clinical Laboratory Operations, Atreca, Inc., will present "GeoMx DSP WTA Platform TCR Alpha Program Collaboration."

Poster: Multi-omic dissection of immunotherapy response in groups in non-small cell lung cancer
Arutha Kulasinghe, Ph.D., NHMRC Research Fellow, Queensland University of Technology
This study utilized spatial transcriptomics methods, including the GeoMx DSP and multiplex IHC, to define the tumor/stroma compartment specific proteome and transcriptome from a cohort of 2nd line immunotherapy treated non-small cell lung cancer patients.

Poster: Development of a custom high-plex GeoMx digital spatial profiler breast cancer protein biomarker assay
Christopher Corless, M.D., Ph.D., Oregon Health & Science University
This study’s goal was to develop a high-plex assay to simultaneously quantitate 27 established and novel breast cancer (BC)-related immune protein and phosphoprotein biomarkers using the GeoMx DSP. The custom assay performance was compared to standard, immunohistochemistry-based clinical BC biomarker assays (e.g., ER, PR, HER2) across the spectrum of BC subtypes and in multiple laboratories with statistically significant concordance.

Poster: A single-cell, spatial multi-omics atlas and cellular interactome of all major skin cancer types
Quan Ngyuen, Ph.D., University of Queensland
Alongside other multi-omics tools, CosMx SMI was used to generate the first spatial single-cell atlas and cellular interactome of all major skin cancer types (squamous cell carcinoma, basal cell carcinoma, and melanoma). Spatial transcriptomics with CosMx SMI reveals cell-type organization into distinct functional tissue layers and identifies cancer-, patient-, and region-specific differences in cell-cell interaction.

Poster: Subcellular characterization of over 100 proteins in FFPE tumor biopsies with CosMx Spatial Molecular Imager
Zach Lewis, Ph.D., NanoString Technologies
108 proteins were imaged in a breast cancer biopsy using the CosMx Spatial Molecular Imager, representing one of the highest-plex protein imaging studies. CosMx encoding and chemistry enable high-throughput, short-turnaround protein imaging studies on the same instrument as the CosMx single-molecule RNA assay.

Poster: Multi-omic analysis of whole transcriptome and high plex protein assays on a single FFPE slide
Shilah Bonnet, Ph.D., NanoString Technologies NanoString Technologies
The newly developed GeoMx Spatial Proteogenomic workflow enables the co-detection of protein (>100-plex) and RNA (up to 21,000-plex) from a single FFPE slide. The performance of the Proteogenomic workflow has been confirmed on various cell pellets and tissue types.

Oral: AACR (Free AACR Whitepaper) NextGen Star, Will Hwang, MD, PhD
April 11, 11:26-11:41 am CST
As an AACR (Free AACR Whitepaper) NextGen Star, Will Hwang, M.D., Ph.D., radiation oncologist and research fellow, Massachusetts General Hospital Cancer Center/Harvard Medical School, will present, "Multicellular spatial community featuring a novel neuronal-like malignant phenotype is enriched in pancreatic cancer after neoadjuvant chemotherapy and radiotherapy."