On April 13, 2023 Affini-T Therapeutics, Inc., a precision immunotherapy company unlocking the power of T cells against oncogenic driver mutations, reported that Loïc Vincent, Ph.D., Chief Scientific Officer and Christopher A. Klebanoff, M.D., physician-scientist at Memorial Sloan Kettering Cancer Center (MSK), who also serves as Scientific Co-founder and Advisor, Affini-T Therapeutics, are presenting data from the company’s T cell receptor (TCR) T cell therapy program targeting KRAS G12D mutations, at this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando (Press release, Affini-T Therapeutics, APR 13, 2023, View Source [SID1234630070]).

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"At Affini-T, we are targeting oncogenic drivers utilizing TCR-engineered T cells equipped with new synthetic biology elements capable of addressing some of the major obstacles in treating solid tumors, including T cell exhaustion and functional durability," said Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics. "Similar to our previously reported KRAS G12V data, our new preclinical data show a promising activity and tolerability profile in targeting KRAS G12D mutation that supports our mission to eradicate difficult to treat solid tumors with precision immunotherapies. Leveraging our platforms, TAILORTM, TUNETM and THRIVETM, we look forward to working with Dr. Klebanoff to progress our programs for patients with solid tumor cancers, including lung, colorectal and pancreatic cancer."

Oral presentation details are as follows:

Preclinical development of safe and effective T cell receptors specific for mutant KRAS G12D peptide

Abstract #1127, Session MS.CL07.01 – Immunotherapy
Session Date/Time: April 16, 3:52 pm – 4:07 pm ET
Presenting Author: Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics
Summary: T cell receptors (TCRs) directed against KRAS G12D mutant peptide/HLA-A*11:01 complex were isolated and prioritized based on specificity, functional avidity, and cytotoxicity, and were subsequently engineered into primary CD4+ and CD8+ T cells. The in vitro and in vivo preclinical data demonstrate a promising activity and tolerability profile of the KRAS G12D mutant TCR-engineered CD4+ and CD8+ T cell therapy. The study supports the planned clinical development of this novel KRAS G12D mutant TCR-engineered CD4+ and CD8+ T cell therapy for treating patients with KRAS G12D mutant / HLA-A*11:01 cancers.
Oral presentation details are as follows:

Immunogenicity and therapeutic targeting of recurrently mutated ‘public’ neoantigens

Session SY18 – Dharma Master Jiantai Symposium in Targeted Therapy: Cellular Therapies for Cancer
Session Date/Time: April 18, 12:35 pm-12:55 pm ET
Presenting Author: Christopher A. Klebanoff, M.D., Associate Member and Attending Physician, Laboratory Head, Human Oncology and Pathogenesis Program, and Member Investigator, Center for Cell Engineering at MSK; and Scientific Co-founder and Advisor, Affini-T Therapeutics
Summary: This study reports key data regarding expression of the mutant and wild type KRAS peptides by transformed and normal cells, and the discovery and characterization of a panel of patient-derived TCRs directed against the KRAS G12D mutant peptide/HLA-A*11:01 complex in vitro and in vivo.
"The findings we are presenting at AACR (Free AACR Whitepaper) 2023 are the result of outstanding scientific collaboration focused on using innovation to overcome bottlenecks that previously limited progress in the field," said Dr. Klebanoff. "I am hopeful that in future years we will see further advances resulting from our research lead to new mutation-specific TCR immunotherapies for patients with cancers that currently lack curative treatments.

On April 13, 2023 Agilent Technologies Inc. (NYSE: A) reported the launch of the Agilent SureSelect Cancer CGP Assay designed for somatic variant profiling for a broad range of solid tumor types (Press release, Agilent, APR 13, 2023, View Source [SID1234630069]). The pan-cancer assay design is based on an NGS panel comprising 679 genes globally curated from leading cancer databases and in partnership with key clinical cancer researchers. The assay workflow is efficient, automatable, and flexible, making tumor molecular profiling more accessible to the broad clinical research community.

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The biomarkers include key classes of somatic variants (SNVs, CNVs, indels, translocations, de novo gene fusions), along with the immuno-oncology biomarkers TMB (tumor mutational burden), and MSI (microsatellite instability) to aid clinical and translational researchers in investigating potential cancer therapeutics. Based on Agilent’s industry-leading library prep and target enrichment chemistry, this high-performance assay provides up-to-date, globally curated biomarker content for comprehensive molecular profiling of solid tumors, supports as low as 10 ng of input, and incorporates walkaway automation to improve lab efficiency and productivity. The workflow incorporates flexible data analysis options, including Alissa Interpret for tertiary analysis and reporting, customer bioinformatics pipelines, and third-party software.

"We’re pleased to commercialize the SureSelect Cancer CGP assay, which leverages our SureSelect chemistry that can accommodate a low amount of starting material so that scientists can profile more quantity-limited samples," explained Ronda Allen, Ph.D., vice president and general manager, Genomics Division at Agilent. "Library preparation and target enrichment can be automated either on the benchtop Magnis NGS prep system, which will markedly improve workflow efficiency, reducing the hands-on time from hours to only 15 minutes, or on the Bravo NGS workstation, for scaling up to 96 samples per run."

Dr. Alistair Ritchie, sequencing laboratory manager at Glasgow Precision Oncology Laboratory (GPOL), shared his experience with the assay. "The comprehensive coverage of the CGP assay means we can batch DNA from any solid tumor on a single run to streamline our workflow," he said. "Our team has come to rely on the Agilent SureSelect XT HS2 method for all our target enrichment assays. We have never used a method that gives us such reproducible results with such a low input amount."

"The release of the SureSelect Cancer CGP assay, as well as the recent acquisition of Avida Biomed, demonstrates Agilent’s commitment to developing high-performing NGS tools for an expanding oncology portfolio, accelerating the advancement of precision oncology. We are proud to partner with clinical researchers and leading cancer centers, such as Glasgow Precision Oncology Laboratory," added Allen.

Agilent is an industry leader with a continuously growing portfolio of world-class chemistries and technologies and has an established presence as a global provider and partner for biomarker analysis and companion diagnostics across the precision oncology sector.

On April 13, 2023 Nucleix, a liquid biopsy company revolutionizing cancer treatment by detecting the disease earlier, reported that it will premiere data from its early lung cancer detection discovery platform, the Nucleix EpiCheck Lung Atlas, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Event in Orlando, April 14-19 (Press release, Nucleix, APR 13, 2023, View Source [SID1234630068]). The proprietary Lung Atlas was constructed and developed as part of a multi-institutional effort to map epigenetic and genomic changes associated with early-stage lung cancer, particularly stage I disease.

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Presentations at AACR (Free AACR Whitepaper) include:

Development of a Genome-Wide Multiomic Atlas of Early-Stage Lung Cancer Enables Identification of Novel Methylation Biomarkers for Disease Detection Beyond TCGA

Session date and time: April 17 at 1:30pm ET
Machine-Learning-Based Epigenetic Detection of Early-Stage Lung Cancers Using the EpiCheck Liquid Biopsy Platform

Session date and time: April 18 at 1:30pm ET
"When lung cancer is detected early, it is more likely that patients will survive the disease," said Chris Hibberd, CEO, Nucleix. "Currently though, most patients are diagnosed with late-stage cancer, even though research has shown that five-year survival rates are up to 10 times greater when lung cancer is detected early.i Results demonstrate the strength of Nucleix’s Lung EpiCheck assay and our differentiated approach for the discovery and identification of novel biomarkers for non-invasive lung cancer screening. We are leveraging these findings to advance a new generation of Lung EpiCheck, which incorporates novel markers from the Lung Atlas and is optimized to detect minute cancer epigenetic signals with greater sensitivity. The next step is well underway as we evaluate the new assay in the Sightline Trial, a 5,000 patient multicenter study in high-risk current and former smokers."

Currently there are limited options for early lung cancer detection and only 10% of the nearly 15 million high-risk smokers recommended to receive low-dose CT imaging adhere to current guidelines.ii The Lung Atlas will aid in Nucleix’s development of the next generation of clinical assays. Nucleix’s Lung EpiCheck analyzes changes in multiple methylation markers to screen for lung cancer using a non-invasive blood sample, with a focus on testing individuals who are at high-risk based on smoking history. Lung EpiCheck has been optimized to focus on sensitivity, so that physicians have a better chance of early detection and patients have a better chance of successful treatment.

Learn more about Nucleix’s Lung EpiCheck.

On April 13, 2023 Affini-T Therapeutics, Inc., a precision immunotherapy company unlocking the power of T cells against oncogenic driver mutations, reported a licensing agreement with MSK (Press release, Affini-T Therapeutics, APR 13, 2023, View Source [SID1234630067]). As a result of the collaboration, which includes a sponsored research agreement with MSK’s Klebanoff lab, Christopher A. Klebanoff, M.D., Associate Member and Attending Physician, Laboratory Head, Human Oncology and Pathogenesis Program, and Member Investigator, Center for Cell Engineering at MSK, will join Affini-T as a Scientific Co-founder and Advisor.

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"We are committed to pushing forward a first-in-class pipeline of treatments targeting oncogene driver mutations for patients with solid tumor malignancies," said Jak Knowles, M.D., Co-founder, President and Chief Executive Officer, Affini-T Therapeutics. "In addition to his role as a leading cancer researcher and medical oncologist at MSK, Dr. Klebanoff and his lab team bring valuable insights into tumor biology, oncogene-specific targeting, T cell fitness within solid tumors, translational medicine and more to our company. We’re pleased to have him as part of our outstanding scientific team and look forward to working together to advance meaningful therapies for patients in need."

Dr. Klebanoff is deeply involved in translational research, which fuels the discovery cycle at MSK across multiple domain areas. "The Klebanoff/Affini-T collaboration embodies MSK’s longstanding commitment to innovation with impact, using bench-to-bedside research to transform cancer care for patients around the globe," said Gregory Raskin, MD, Senior Vice President, Technology Development at MSK.

"Core to the PICI mission is the need to overcome hurdles and forge collaborations. I am thrilled that Chris Klebanoff of MSK and Affini-T Scientific Co-founder Phil Greenberg of the Fred Hutchinson Cancer Center, two exceptional PICI affiliated researchers, have joined forces to form a powerful partnership," said Sean Parker, Executive Chairman of the Parker Institute for Cancer Immunotherapy and Board Observer, Affini-T Therapeutics. "Chris Klebanoff is an esteemed scientist with significant experience in KRAS targeting and T cell receptor development, and I am delighted to welcome him in this critical role at Affini-T."

Prior to joining MSK, Dr. Klebanoff was a Howard Hughes Medical Institute Research Scholar and Assistant Clinical Investigator at the National Cancer Institute (NCI) in Bethesda, Maryland. Dr. Klebanoff has contributed to the successful early phase development of numerous T cell-based therapies, notably Yescarta (axicabtagene ciloleucel) at NCI. He is an elected member of the American Society for Clinical Investigation (ASCI) and has received prestigious awards including the Damon Runyon Clinical Investigator Award, a National Institutes of Health (NIH) MERIT Award and NIH Fellows Award for Research Excellence.

"As a practicing medical oncologist, my singular professional focus and that of my lab is to address the urgent needs of patients with cancer. While continuing in my work as a physician-scientist at MSK, I am proud to be joining a team passionately working towards a shared mission of engineering transformative therapies for patients with solid tumors," said Dr. Klebanoff. "Affini-T is rapidly advancing its ground-breaking research toward the clinic, and I am honored to join its distinguished group of scientific co-founders and advisors whose pioneering research complements our work in the Klebanoff laboratory.

On April 13, 2023 -Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) ("Infinity" or the "Company"), a clinical-stage biotechnology company developing eganelisib, a potential first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic, reported upcoming presentations including data on eganelisib by Infinity’s collaborator, Professor Judith A. Varner of the UCSD Moores Cancer Center, La Jolla, California, at the 2023 Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) to be held April 14 – 19, 2023 in Orlando, Florida (Press release, Infinity Pharmaceuticals, APR 13, 2023, View Source [SID1234630066]).

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Highlights of the presentations include preclinical and translational data further reinforcing the mechanism of action of PI3K-γ inhibition:

Single cell transcriptomics data showing PI3K-γ knockout switches tumor associated macrophages in head and neck squamous cell carcinoma (HNSCC) and non small cell lung cancer (NSCLC) tumor models to activated, antigen-presenting, T cell-stimulating macrophages.
Preclinical data supporting tumor growth delay of HNSCC tumor models in PI3K-γ knockout mice is mediated by intra-tumoral interleukin-12, interferon gamma and CD8+ T cells, key drivers of immune response to cancer.
Translational data from the MARIO-275 clinical trial showing increased systemic immune activation in patients treated with nivolumab in combination with eganelisib over nivolumab alone, with enrichment of genes from interferon signaling, antigen presentation, and T cell receptor pathways.
Translational data from the MARIO-3 clinical trial, showing immune activation within the tumor microenvironment in patients treated with eganelisib, nab-paclitaxel and atezolizumab, with up-regulation of interferon signaling, antigen presentation, and T cell receptor pathways.
Following translational data from MARIO-1 indicating increased expression of the TGF-β activating integrin αVβ8 in HNSCC patients treated with combination of eganelisib and nivolumab, initial preclinical studies showing anti-αVβ8 monoclonal antibody treatment prevents growth of HNSCC tumor model in PI3K-γ knock-out mice.
"Our presentations describe exciting aspects of the role of PI3K-γ as a fundamental molecular switch controlling immune response by myeloid cells in the tumor microenvironment," said Professor Varner. "Our preclinical data suggest key roles for antigen-presenting activated macrophages, intra-tumoral IL-12, IFN-γ release and activated CD8+ T cells in mediating the effect of PI3K-γ knockout or PI3K-γ inhibition in tumor models. In line with our preclinical studies, emerging translational data from the MARIO-275 and MARIO-3 clinical trials support the mechanism of action of eganelisib through reprogramming and activation of tumor associated macrophages to reshape the tumor microenvironment and favor anti-tumor activity. Altogether, these data continue to underscore the potential of eganelisib as a next generation macrophage reprogramming immunotherapeutic, in combination with checkpoint inhibitors or potentially new immuno-oncology agents like anti-αVβ8 monoclonal antibodies."

Details of the presentations are as follows:

Presentation time: Saturday, April 15, 2023, 8:30am-8:50am EDT
Title: Macrophages rule in cancer
Session: ED034 – Antigen Presentation: The Macrophage-Dendritic Cell Debate
Presenter: Judith A. Varner

Presentation time: Tuesday, April 18, 2023, 10:20am-10:40am EDT
Title: Basic and clinical impacts of targeting myeloid cells in tumors
Session: Session SY14 – Next Generation of Myeloid Checkpoints in Cancer
Presenter: Judith A. Varner