On November 12, 2021 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that pre-clinical data from its proprietary, multi-specific NK cell engager platform, ANKETTM, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in collaboration with partner, Sanofi (poster #852) (Press release, Innate Pharma, NOV 12, 2021, View Source [SID1234595397]).

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Specifically, the companies will share new data on IPH6101/SAR443579, the first NKp46/CD16-based NK cell engager using Innate’s proprietary multi-specific antibody format1 that targets CD123 on acute myeloid leukemia (AML) cells and now co-engages NKp46 and CD16a on NK cells.

CD123 is an attractive target as it is expressed at high levels in the majority of AML patients2. However, overcoming resistance to antibody-dependent cellular cytotoxicity (ADCC) has been a challenge.

In pre-clinical studies, IPH6101/SAR443579 demonstrated potent antitumor activity against AML cell lines, including those resistant to ADCC by a comparator anti-CD123 antibody. IPH6101/SAR443579 also promoted strong and specific NK-cell activation and induced cytokine secretion only in the presence of AML target cells.

In addition, IPH6101/SAR443579 had sustained pharmacodynamic effects in non-human primates, combining efficient depletion of CD123-expressing cells with minor systemic cytokine release in comparison to T-cell engagers. As expected, it also had a favorable safety profile.

"There is a strong need to develop effective therapies to treat acute myeloid leukemia, the most common acute leukemia in adults," said Pr. Eric Vivier, Ph.D., DVM, Chief Scientific Officer at Innate Pharma. "We’re pleased to present pre-clinical data on IPH6101/SAR443579 that shows antitumor activity against AML, and more specifically, the potential of engaging NK cells through NKp46 and CD16 via our ANKETTM technology. We look forward to seeing Sanofi dose the first patient in the clinic with this molecule soon."

Innate will also present a second ANKETTM poster (poster #851) at SITC (Free SITC Whitepaper) entitled, "Harnessing Innate Immunity in Cancer Therapies: the Example of Natural Killer Cell Engagers." The data will highlight the induction of a unique NK cell activation pathway by its tetra-specific ANKETTM molecule. The abstract can be accessed here.

About ANKETTM:

ANKETTM (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer. The Company’s latest innovation, its tetra-specific ANKETTM molecule, is the first NK cell engager technology to engage activating receptors (NKp46 and CD16), a tumor antigen and an interleukin-2 receptor (via an IL-2 variant, IL-2v) via a single molecule. This leverages the advantages of harnessing NK cell effector functions against cancer cells and also provides proliferation and activation signals targeted to NK cells.

In pre-clinical studies, Innate’s tri-1 and tetra-specific ANKETTM technologies promote potent NK cell activation, cytotoxicity and efficient control of tumor growth in pre-clinical models. This versatile fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer.

About IPH6101/SAR443579:

In the first research program of the Sanofi collaboration, IPH6101/SAR443579, the first NKp46/CD16-based NK cell engager using Innate’s proprietary multi-specific antibody format1, has shown antitumor activity in pre-clinical models, including supportive pharmacokinetic/pharmacodynamic (PK/PD) and safety data in non-human primate studies leading to its selection as a drug candidate for development.

About the Innate-Sanofi agreement:

The Company has a research collaboration and licensing agreement with Sanofi to apply Innate’s proprietary technology to the development of innovative multi-specific antibody formats engaging NK cells through the activating receptors NKp46 and CD16 to kill tumor cells.

Under the terms of the license agreement, Sanofi will be responsible for the development, manufacturing and commercialization of products resulting from the research collaboration. Innate Pharma will be eligible to up to €400m in development and commercial milestone payments as well as royalties on net sales.

On November 12, 2021 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision oncology biopharmaceutical company, reported that Susan Molineaux, Ph.D., the company’s founder, president and chief executive officer, will present at the 2021 Jefferies London Healthcare Conference (Press release, Calithera Biosciences, NOV 12, 2021, View Source [SID1234595428]).

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The presentation will be available for on-demand viewing starting Thursday, November 18 at 3:00 a.m. Eastern Time, and can be accessed through the Investors section of the Company’s website at www.calithera.com. The replay of the webcast will be available on the Company’s website for 30 days.

On November 12, 2021 Candel Therapeutics, Inc. (Nasdaq: CADL), a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported presentation of novel biomarker data from their ongoing phase 1 open-label, dose-escalation clinical trial of CAN-3110 in patients with recurrent high-grade glioma (HGG) (Press release, Candel Therapeutics, NOV 12, 2021, View Source [SID1234595450]). CAN-3110 is an HSV replication-competent oncolytic virus engineered to provide selective killing of cancer cells while sparing neighboring healthy cells. The presentation entitled "Detection of viral antigen and immune activation after intra-tumor injection of CAN-3110 (ICP-34.5 expressing HSV-1 oncolytic virus) in patients with recurrent high-grade glioma" was presented at the SITC (Free SITC Whitepaper) 36th Annual Meeting by Candel’s Vice President and Head of Research, Francesca Barone, MD, PhD.

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During the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2021, Candel reported preliminary clinical data demonstrating an overall survival of 11.7 months in this difficult-to-treat patient population. The current presentation, focused on the biological findings of this study, showed the ability of CAN-3110 to induce immune activation both locally in the tumor microenvironment and systemically in peripheral blood.

Histologic analysis and molecular profiling of post-treatment brain samples demonstrated persistence of viral antigen associated with significant T-cell infiltration in the tumor parenchyma as well as a molecular signature consistent with local activation of innate and adaptive immunity. Analysis of post-treatment serum samples showed upregulation of pro-inflammatory cytokines and chemokines. These findings collectively indicate that CAN-3110 treatment can induce both local and systemic immune activation associated with an encouraging clinical response.

"There is a critical need for treatment options for patients with recurrent high-grade glioma. The data from this trial support the mechanistic approach of tumor cell-specific replication that was the intent of the CAN-3110 design," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel Therapeutics. "The biomarker data presented at SITC (Free SITC Whitepaper), in conjunction with the overall survival data previously reported at ASCO (Free ASCO Whitepaper), are encouraging signals as we endeavor to bring novel oncolytic viral immunotherapies to patients with cancer."

Details from the presentations will be available on Candel’s company website at View Source

About CAN-3110

CAN-3110 is an HSV replication-competent oncolytic virus engineered to enhance selective killing of cancer cells while sparing neighboring healthy cells. CAN-3110 selectively expresses ICP34.5, a key gene in HSV replication, in tumor cells that overexpress nestin, a cytoskeletal protein. Nestin is highly expressed in high-grade glioma cells and other tumor tissues, but it is absent in healthy adult brain tissue.

Candel is evaluating the effects of treatment with CAN-3110 in recurrent high-grade glioma.

For more information on this clinical study, please visit View Source

On November 12, 2021 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, reported that the company will co-present with Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), three posters at the 36th Annual Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Nov. 10 – 14, 2021 from research into diagnostic tests of treatment response of NSCLC patients to immune checkpoint inhibitor therapy (Press release, Biodesix, NOV 12, 2021, View Source [SID1234595467]).

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"Biodesix is committed to performing research with biopharma companies, while pursuing, discovering and developing applications that can help physicians and researchers address the needs of patients with lung cancer who will benefit from quick, actionable test results," said Scott Hutton, CEO, Biodesix. "We are pleased to present data on two tests that have the potential to become instrumental in the care of patients with non-small cell lung cancer (NSCLC). Additionally, our data highlights novel methods that we have developed to provide an explanation as to how our proprietary Diagnostic Cortex Artificial Intelligence (AI) platform combines molecular attributes to produce individual patient results. This data is extremely important because we expect that this will provide clarity and transparency to how our AI-based tests work and how a diagnostic test may better predict efficacy of various treatments in the most appropriate patient populations. We are proud of the data being presented at SITC (Free SITC Whitepaper) as it underscores our commitment to the lung cancer community."

The three Genentech/Biodesix-sponsored posters include the following:

Abstract #26: Validation of the Primary Immune Response (PIR) test in advanced non-small cell lung cancer (NSCLC): blinded retrospective analyses from the POPLAR and OAK trials

Findings will be presented from blinded, retrospective analyses of two Genentech multicenter, open-label RCT clinical studies comparing atezolizumab versus docetaxel in patients with previously treated NSCLC (POPLAR Phase 2 and OAK Phase 3). The Biodesix liquid-biopsy mass spectrometry-based Primary Immune Response (PIR) test stratified outcomes for patients treated with the study drug in second and third line, predicting overall survival, even when adjusted for PD-L1 expression and clinical factors. The importance of understanding who will or will not respond to immunotherapy is critical and identifying predictive biomarkers of immunotherapy response has become a growing focus of immune-oncology research. This study highlights the potential of biomarkers of immune checkpoint inhibitors, such as the PIR test, to support patient stratification.

Abstract #28: Predictions of outcomes and benefit of immune checkpoint inhibitor treatment in non-small cell lung cancer require information on both tumor and host biology

Findings from a Genentech blinded, retrospective study of second- and third-line NSCLC patients in the OAK Phase 3 clinical study comparing atezolizumab versus docetaxel in patients with previously treated NSCLC will be presented. The study demonstrated that the Biodesix Anti-PD-L1 Response Test (ART), based on mass spectrometry of pretreatment serum, stratifies outcomes in both treatment arms overall and in all PD-L1 subgroups. The Biodesix ART test was shown in independent validation to predict outcomes for NSCLC patients treated in a large Phase 3 study and was discovered and developed for Genentech as a part of a partnership between the two companies.

Abstract #831: Exact Shapley Values for explaining complex machine learning based molecular tests of checkpoint inhibitors: potential utility for patients, physicians, and translational research

Data will show how Exact Shapley Values (SVs), a technique developed by Biodesix, can explain how complex machine learning (ML)-based tests combine molecular attributes to produce individual patient results. Exact SVs can be obtained for certain ML architectures used in molecular test development, revealing the overall relative importance of attributes used in such molecular tests. Specifically, this study evaluated SVs for the Biodesix Anti-PD-L1 Response Test (ART), that was shown in independent validation to predict outcomes for NSCLC patients treated in a large Phase 3 study. By subgrouping patients according to ART results, different patterns of SVs were determined, potentially revealing different biologies that were predictive of overall survival outcomes. Exact SVs explain how complex ML-based tests combine molecular attributes to produce individual patient results.

On November 12, 2021 PathAI, a global provider of AI-powered technology applied to pathology reported that results from a recent exploratory biomarker analysis on digitized slides to apply AI-predicted CD8 topology assessment of patients with advanced melanoma will be presented at the annual Meeting of Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), November 10-14 2021 (Press release, PathAI, NOV 12, 2021, View Source [SID1234595483]).

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The results will be shared in two posters, Lee et al. The utility of AI-powered spatial classification of intratumoral CD8+ immune-cell topology in predicting overall survival in patients with melanoma as part of the CheckMate 067 clinical trial, and Glass et al. Machine Learning Models Can Quantify CD8 Positivity in Melanoma Clinical Trial Samples.

PathAI developed Machine Learning (ML) models to quantify CD8+ T cells in digitized whole slide images (WSI) of melanoma patient samples, and validated their performance against a consensus of pathologists on a held-out data set. These models were deployed on CD8-stained biopsy samples collected from patients with previously untreated advanced melanoma in the CheckMate 067 clinical trial. The AI-based predictions of CD8 positivity were used by ML models created by Bristol Myers Squibb to categorize each WSI by spatial pattern and density of CD8+ T cell infiltration (CD8 topology) as desert (deficient in CD8+ T cells), excluded (CD8+ T cells at the tumor boundaries and surrounding stroma), or inflamed (CD8+ T cells within the tumor parenchyma).

PD-L1 stained tumor cell positivity scores of either PD-L1 <1% or PD-L1 >1%, collected previously during the CheckMate 067 clinical trial, were combined with the CD8+ spatial phenotype scores to create a composite biomarker. Correlations between overall survival of patients in CheckMate 067 and CD8+ spatial phenotype alone, or the composite biomarker identified a subpopulation of patients with PD-L1 expression < 1%, and a CD8+-excluded tumor spatial pattern that benefited significantly from the drug combination treatment (nivolumab and ipilimumab) compared with PD-L1 negative patients with a CD8+-inflamed tumor spatial pattern (P = 0.002). No difference in survival between excluded and inflamed phenotypes was observed for patients treated with monotherapy (nivolumab alone) (P = 0.41), nor with any patients with PD-L1 >1%.

The data presented here suggest that in addition to PD-L1 positive patients, PD-L1 negative CheckMate 067 patients who were also CD8+ in specific subregions of tumors had overall survival benefit when treated with ipilimumab plus nivolumab combinations compared to those that were treated with ipilimumab monotherapy.

Together, these publications highlight the promise of ML-based CD8+ phenotype scoring to reveal populations of patients that might have the greatest benefit from existing treatments.