On November 7, 2022 Lunit (KRX: 328130.KQ) reported that it will present three abstracts at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting, to be held in Boston, MA, and virtually from Nov. 8 – 12 (Press release, Lunit, NOV 7, 2022, View Source [SID1234623321]).

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As a leading provider of state-of-the-art cancer diagnostic technology, Lunit has focused on developing novel AI biomarkers for application in immunotherapy. Since 2019, the company has released groundbreaking findings based on its AI-powered tissue analysis platform, Lunit SCOPE, demonstrating the software’s predictive value in identifying patients eligible for immunotherapy.

This year, Lunit’s presentations at SITC (Free SITC Whitepaper) 2022 will highlight the effectiveness of Lunit SCOPE IO in accelerating immunotherapy clinical trials and drug development.

Lunit SCOPE IO analyzes a patient’s cancer tissue slide image by observing the distribution of tumor-infiltrating lymphocytes (TILs) — one of the representative immunocytes that fight cancer cells. Based on the spatial distribution of TILs and cancer cells in the tumor microenvironment, Lunit SCOPE IO identifies the tissue sample as one of three immune phenotypes: inflamed, immune-excluded, or immune-desert.

One of the studies to be presented aimed to analyze the multi-cancer landscape of HER2-low expression using clinical data, pathological slides, and genetic expression registered in the National Cancer Institute’s "The Cancer Genome Atlas" (TCGA).

To understand the immune microenvironment of HER2-expressing tumors, Lunit’s researchers performed a spatial analysis of tumor-infiltrating lymphocytes (TILs) in association with HER2 status. As a part of this study, Lunit SCOPE IO was applied to analyze pathological slides from 7,322 patients across 22 cancer types obtained from the TCGA data set.

"The recently approved next-generation HER2 antibody-drug conjugate (ADC) has opened the door to more effective treatments for HER2-low breast cancer, which previously had limited treatment options. Based on the existing studies that HER2-expressed cancer exhibits a lower immune response, it has become important to gain more insight into the tumor microenvironment for future combinatory strategies with immune checkpoint inhibitors," explained Chan-Young Ock, Chief Medical Officer of Lunit.

"Lunit SCOPE IO, an artificial intelligence-powered H&E analyzer, can provide immune phenotypes by performing spatial analysis of tumor-infiltrating lymphocytes (TILs). This study shows Lunit SCOPE IO’s possibility to further identify possible responders for the combination therapy," he added.

Lunit will also present findings from a meta-analysis study comparing the discontinuation rates of immunotherapy alone (IO-only) and immunotherapy combined with chemotherapy (chemo-IO), respectively, due to treatment-related adverse events (TRAE). 41 clinical trials, including over 13,000 patient cases, were examined. Compared to IO-only, the results indicated that chemo-IO has a significantly higher TRAE-related discontinuation rate.

TRAE-related discontinuation may lead to suboptimal treatment outcomes, warranting the discovery of a novel biomarker that can accurately predict which patients will achieve a durable response from IO-only without early treatment discontinuation. Thus, this study can be a key reference to prove Lunit SCOPE IO’s clinical validity to omit the unnecessary potential risks that may result from chemo-IO.

Another study co-authored by Lunit aims to evaluate the clinical efficacy of NeoImmuneTech’s NT-I7 (efineptakin alfa) and pembrolizumab to support T-cell infiltration in microsatellite-stable colorectal (MSS-colorectal) and pancreatic cancer patients with no standard treatment option.

In this clinical trial, pre-treatment and on-treatment biopsies were analyzed by Lunit SCOPE IO to objectively measure the increase in TIL infiltration. While objective measurement of TIL in small biopsied samples can be challenging, Lunit SCOPE IO is able to sensitively detect TIL in these difficult-to-analyze tissues — this indicates a practical application for the AI model in a clinical trial space.

"We are pleased to return to SITC (Free SITC Whitepaper) this year to showcase new findings validating the effectiveness of Lunit’s AI biomarker platform as a practical research tool for clinical study," said Lunit CEO Brandon Suh. "We will continue to work toward our goal to offer optimized treatment to cancer patients through AI."

On November 7, 2022 Cytovia Therapeutics, Inc., a biopharmaceutical company empowering natural killer (NK) cells to fight cancer through stem cell engineering and bispecific antibodies, reported new preclinical data for its TALEN gene-edited, iPSC-derived NK (iNK) cells and GPC3-targeted Flex-NK bispecific antibodies (Press release, Cytovia Therapeutics, NOV 7, 2022, View Source [SID1234623320]). The data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 37th Annual Meeting (SITC 2022) taking place in Boston, MA, and virtually November 8-12th, 2022.

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"We’re delighted to see further progress on our lead GPC3-targeted Flex-NK bispecific antibody program, with a pre-clinical package that supports clinical evaluation in 2023," commented Cytovia CEO Dr. Daniel Teper. "Additionally, we have now generated TALEN gene-edited iNK cells and demonstrated enhanced antitumor activity. Cytovia is the first company to develop both its own immune cell engagers and natural killer cells, with the potential for enhanced efficacy in cancers with significant unmet medical needs such as Hepatocellular Carcinoma."

The presentations show that Cytovia’s allogeneic iNK cell product CYT-100 demonstrated increased time-dependent killing of Hep3B tumor spheroids and sensitivity to cytokine activation & expansion potential. Cytovia’s GPC3-targeted bispecific antibody CYT-303 demonstrated potent ADCP and CDC against Hep3B tumors as well as Hep3B tumor spheroid and serial killing activities in the presence Cytovia’s allogeneic iNK cell product CYT-100 and PBNKs in a dose-dependent manner. Preclinical pharmacokinetics and safety study results in monkeys fully support CYT-303 clinical development.

Cytovia’s next-generation iNK cell platform combined with TALEN gene-editing robustly and reliably generated single-cell edited iPSC clones, which were expanded and differentiated into functionally improved iNK cells. The data shows that iNK cells edited with an IL-15 knock-in and TGFβR2 knock-out result in enhanced antitumor activity. The editing and manufacturing process will enable clinical evaluation of these product candidates, both alone in combination with CYT-303.

On November 7, 2022 Actym Therapeutics, a Berkeley-based biotechnology company focused on the discovery and development of transformational immunotherapies to treat cancer, announced today that an abstract highlighting detailed in vivo and in vitro preclinical data of its lead candidate, ACTM-838, was accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, to be held virtually and at the Boston Convention & Exhibition Center from November 8 to 12, 2022 (Press release, Actym Therapeutics, NOV 7, 2022, View Source [SID1234623319]). ACTM-838 is Actym’s lead candidate from its proprietary STACT platform and encodes an engineered IL-15 payload (IL-15plex) and engineered STING payload (eSTING). The data showed ACTM-838 to offer powerful efficacy as a single agent, including when used in checkpoint refractory tumors, and to work synergistically when used in combination with anti-PD1 therapies.

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"The data we are presenting at SITC (Free SITC Whitepaper) highlights the power of ACTM-838 to overcome the highly immunosuppressive tumor microenvironment and generate durable anti-tumor immunity in preclinical models," said Christopher Thanos, Ph.D., Actym’s President, CEO, and Cofounder. "ACTM-838 is systemically delivered, with potent, tumor-specific effects. These preclinical data give us confidence in our approach to comprehensively and broadly re-program the tumor microenvironment as we prepare to enter the clinic in 2023."

Research highlights include:

Broad and comprehensive reprogramming of the immunosuppressive tumor microenvironment (TME) to an anti-tumor immunophenotype occurs after safe, intravenous dosing with ACTM-838.
Profound immune infiltration and activation across T-cells, macrophages, dendritic cells, and B-cells, after treatment with ACTM-838.
Potent ACTM-838 single agent efficacy and highly synergistic efficacy in combination with anti-PD1 therapies in checkpoint refractory breast and colon cancer tumor models, inducing complete responses in both regimens. As a monotherapy, ACTM-838 generated durable immunity upon re-challenge in cured animals.
Increased T-cell infiltration and activation, and decreased T-regs after treatment with ACTM-838. Myeloid cell re-polarization to a preferred, dual M1/M2 phenotype was also observed.
Overcoming a known immune evasion strategy for tumors (downregulation of MHC class I) and observing MHC class I upregulation in the TME, after ACTM-838 treatment.
"Our preclinical work has shown ACTM-838’s efficacy in transforming the tumor microenvironment both as a potent single agent and in synergy with anti-PD1 therapies," said Chan Whiting, Ph.D., Actym’s Chief Development Officer and Head of Research and Development. "We look forward to entering the clinic next year with this new and potentially powerful therapeutic approach, and bringing hope to cancer patients with limited treatment options."

SITC Presentation Details:
ABSTRACT #1065: ACTM-838, a microbial-based immunotherapy that enriches in solid tumors after IV dosing, reverses the immunosuppressive TME to promote durable anti-tumor immunity, alone and in combination with anti-PD1 in mice
DATE: Thursday, November 10, 2022
TIME: 9:00 AM EST
PRESENTER: Akshata Udyavar, Ph.D., Senior Director, Immunology & Translational Sciences, Actym Therapeutics
LOCATION: Boston Convention & Exhibition Center, Boston, MA USA

On November 7, 2022 Geneos Therapeutics, a clinical stage biotherapeutics company focused on the development of personalized therapeutic cancer vaccines (PTCV), reported positive safety and efficacy data from the first 24 patients (23 evaluable) enrolled in GT-30 (Press release, Geneos Therapeutics, NOV 7, 2022, View Source [SID1234623318]). GT-30 is an ongoing single-arm open-label multi-center Phase 1b/2a study to evaluate safety, immunogenicity, and efficacy of PTCV (GNOS-PV02) administered in combination with plasmid-encoded IL-12 (pIL12) and pembrolizumab in patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progress on, or are intolerant to, first line tyrosine kinase inhibitors (sorafenib or lenvatinib). By RECIST1.1 an overall response rate of 29.2 percent in the modified intent-to-treat analysis (mITT) was observed, including complete responses in two patients as well as a third cancer-free patient who achieved secondary resectability and four additional partial responses. The data will be presented on November 10th in an oral presentation (Abstract #693) by clinical trial investigator, Edward Gane, MD, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting.

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To date, no dose limiting toxicities nor PTCV + pIL12 related serious adverse events (SAEs) or Grade 3 or 4 adverse events (AEs) have been reported. Grade 1 and 2 PTCV + pIL12 related AEs have been transient and mild.
By RECIST1.1, disease control rate is 54.2 percent (13/24; mITT) consisting of two complete responses (CR), five partial responses (PR), six stable disease (SD) and 10 progressive disease (PD).
A third patient (deemed a radiological PR) is cancer-free after a liver primary lesion and two lung metastases all reduced in size to become fully responsive to surgery and radiation therapy.
One patient discontinued treatment due to a non-treatment-related SAE and was deemed unevaluable but included in the mITT analysis.
Novel and expanded T cell clones, predominantly CD8+ with activated phenotype, were identified in 100 percent of evaluated patients via pre-/post-vaccination analysis of T cell receptor (TCR) repertoire in peripheral blood and tumor tissue. These clones trafficked to the tumor microenvironment (TME) by week nine, potentially mediating the observed tumor regressions.
"As a physician who has been managing patients with advanced liver cancer for more than two decades, I am thrilled by the response rate and immunologic activity we are seeing with this promising form of therapeutic cancer vaccination," stated Dr. Gane, professor of medicine at the University of Auckland, New Zealand, hepatologist and deputy director of the New Zealand Liver Unit at Auckland City Hospital. "To see three cancer-free patients out of 23 evaluable in second-line advanced HCC, with a treatment this well tolerated, tells me that personalized therapeutic cancer vaccination may now, finally, be here to stay. If these response rates are maintained as the program advances toward registration, then I see PTCV becoming a core foundation of cancer immunotherapy, not just for HCC, but broadly."

"We’re deeply gratified to see our PTCVs helping patients. The observation that all patients assessed mounted both a CD4+ and CD8+ T cell response to their own neoantigens means that our work to optimize all aspects of an ideal personalized therapeutic cancer vaccine, as well as its method of administration, has borne fruit. Cancer vaccination has always been a powerful idea and we believe these clinical data validate that with all of these technical pieces having come together, meaningful results are even achievable in advanced cancer settings," stated Niranjan Sardesai, PhD, president and chief executive officer of Geneos. "In GT-30, manufacturing timing from biopsy to treatment is six to eight weeks but we have a clear path to reduce this to three to four. Doing so will make PTCVs practical for any cancer treatment setting, whether first-line or later-line, neoadjuvant, or adjuvant," Dr. Sardesai added.

GT-30 Trial of Geneos’ Personalized Therapeutic Cancer Vaccines
In the GT-30 trial, DNA plasmid-encoded personalized therapeutic cancer vaccine (PTCV) together with plasmid-encoded interleukin-12 (pIL12, a T cell-stimulating cytokine) are administered via intradermal injection followed by electroporation (EP) in combination with pembrolizumab. The potential utility of this combination was suggested by preclinical studies which demonstrate the ability of Geneos’ PTCV to rescue PD-1 in murine tumor therapeutic challenge models. Geneos’ PTCVs have been engineered to drive a strong CD8+ T cell response against the tumor. CD8 cells are the killing machines of the immune system, seeking out and destroying cancer cells, but have been difficult to induce using prior vaccine approaches. Adjuvant pIL12 and EP serve to optimize the effectiveness of peripheral vaccination, and their utility is seen by the effective CD4+/CD8+ T cell responses observed to the delivered neoantigens in the GT-30 patients. Meanwhile, each patient’s PTCV is designed based on their unique tumor neoantigens (abnormal mutations and genomic variations produced by cancer cells) and unlike for other personalized platforms, in most every case, Geneos’ PTCVs include all of a patient’s specific neoantigens. This removes any requirement to try to pre-select the "high value" neoantigens accurately and, instead, leaves it to nature to decide which ones will matter for triggering a desired immune response.

Based on the 24-patient data, Geneos has expanded GT-30 to enroll a further 12 patients, with first reports on benchmark overall survival (OS) from the full cohort of 36 anticipated in mid-2023. In parallel, the company is developing plans for a potential registrational trial in advanced HCC with its medical advisors and preparing for discussion with regulatory agencies.

"While overall cancer rates are decreasing worldwide, HCC deaths are rising in the United States and globally, and the etiology of disease is shifting from viral to non-viral causes. HCC is resistant to immune checkpoint therapies in the majority of patients due to the largely immune excluded tumor microenvironment. Therapies that can bring CD8+ T cells into the tumor microenvironment, such as effective therapeutic cancer vaccines targeting cancer neoantigens, can reprogram the tumor microenvironment for checkpoint inhibitor therapy," stated Mark Yarchoan, MD, associate professor of oncology at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, and clinical investigator on GT-30. "The promising data presented at this meeting lend optimism to the important role that PTCVs may play in cancer treatment."

Additional Geneos Abstracts at SITC (Free SITC Whitepaper) Conference
Abstract #691 details a case study from GT-30 of a patient whose PTCV, designed based on the neoantigen content of a liver tumor primary lesion, resulted in a clinical PR. Profound shrinkage and control of the liver lesion resulted, now continuing for over a year. A metastatic adrenal lesion newly developed four months post initial treatment, the neoantigen content of which was similar but not identical to the liver primary lesion: while 16 of the original liver neoantigens remain, all four of the vaccine epitopes with strongest T cell responses were absent in the adrenal lesion. It is believed that this disappearance is an example, at exquisite immunologic detail, of immune pressure applied by a PTCV-induced T cell response. This case study confirms that tumor control, as well as the loss thereof, is being achieved by PTCV-directed immune responses and not by pembrolizumab alone, as no mechanistic theory of PD(L)-1 activity would explain these simultaneous clinical observations.

The ability to understand tumor progression at this level of immunologic detail also offers a credible vision for real world use of PTCV dynamic therapy to counter immune escape. It is straightforward to create a new PTCV in response to evolved neoantigen presentations, such as this patient’s adrenal lesion, which would be co-administered with the original liver-targeted PTCV. Such evolved therapeutic vaccines could be a novel tool when new, or newly unresponsive lesions, present. These data will be presented in the poster session on November 10th by Dr. Yarchoan.

Abstract #692 summarizes the use of circulating tumor DNA (ctDNA) analysis in the GT-30 trial, to monitor tumor burden (progression or reduction). It was concluded that ctDNA may be a useful tool for monitoring disease in a patient specific manner. The ease of sample handling and analysis, and the rapid availability of data, may enable the use of ctDNA monitoring to allow real-time clinical treatment decision making for personalized cancer immunotherapy. These data will be presented in the poster session on November 11th by Dr. Jian Yan, PhD, vice president, research and discovery at Geneos.

On November 7, 2022 OncoHost, a global leader in next-generation precision oncology for improved personalized cancer therapy, reported that it has developed a novel predictive model for clinical benefit of immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients (Press release, OncoHost, NOV 7, 2022, View Source [SID1234623317]). The model is based on proteomic profiling of pre-treatment blood samples, combined with machine learning analysis that accurately predicts clinical benefit probability at twelve months, outperforming the predictive capabilities of the existing PD-L1 biomarker. The study was conducted using OncoHost’s first-of-its-kind PROphet platform, and will be presented as a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting.

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Currently, clinical benefit prediction of ICI therapy and selecting an effective and safe treatment modality (i.e., immunotherapy alone vs. combination of immunotherapy with chemotherapy) relies on PD-L1 expression levels. However, the available assays are only moderately predictive. In addition, the clinical benefit of immunotherapy-based strategies is still limited to a minority of patients, reflecting the need to identify predictive biomarkers of clinical benefit and ultimately improve patient selection for truly personalized treatment plans.

"We are proud to once again be presenting robust scientific evidence on clinical benefit prediction for NSCLC patients," said Michal Harel, Ph.D., director of science and innovation at OncoHost and PI of the study. "Our proprietary machine learning and proteomics-based platform, PROphet, provides two clinical utilities; first, it can successfully predict clinical benefit at twelve months; second, the model, combined with PD-L1 testing, provides a decision-making tool for physicians on whether to administer immunotherapy alone or in combination with chemotherapy for their patients, with a significant effect on overall survival."

The predictive model was developed on a cohort of 339 ICI-treated NSCLC patients taking part in OncoHost’s ongoing, multicenter PROPHETIC clinical trial. Plasma samples and clinical data were collected, and deep proteomic profiling was conducted using SomaLogic’s (NASDAQ: SLGC) SomaScan platform. The model performance was assessed in a blinded validation. PROphet displayed strong predictive capabilities, and successfully identified those patients who would gain long-term benefit from immunotherapy combined with chemotherapy, as well as those who would benefit from immunotherapy alone. This has been an important, unsolved clinical question to date. For the first time in NSCLC, a blood-based test is now able to successfully guide treatment selection by stratifying patients into four subgroups, each one showing distinct overall survival behavior for monotherapy and combination therapy.

"We are proud to have successfully developed a clinical decision support tool that answers a clear question with strong results. By combining PROphet’s output with PD-L1 testing results, our model will assist clinicians in administering a treatment modality that their patient can actually benefit from. This will create a major shift in the care of these patients," said Ofer Sharon, MD, CEO of OncoHost. "It is an exciting time for our company as we are launching our PROphet test in the U.S. for NSCLC patients, and these results only further support our eventual goal of developing a precision oncology tool to improve patient outcomes across the cancer continuum."

The clinical study was conducted in collaboration with, Thoraxklinik Heidelberg University, Mayo Clinic, UC Davis Comprehensive Cancer Center, Sidney Kimmel Medical College at Thomas Jefferson University, The Ohio State University Wexner Medical Center, among other institutions.

The poster will be presented in the poster hall at SITC (Free SITC Whitepaper) on November 10 and 11, 2022, between 9:00 and 21:00 EST and will be available in the Journal for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (JITC) supplement.