On April 11, 2022 Pillar Biosciences, an innovative, next-generation sequencing (NGS) solutions, in-vitro diagnostics (IVD) company, reported the presentation of clinical validation data for the FDA-PMA1 approved oncoReveal Dx Lung & Colon Cancer Assay, along with three additional posters at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Pillar Biosciences, APR 11, 2022, View Source [SID1234611990]).

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"Results of the validation study of Pillar’s oncoReveal Dx Lung & Colon Cancer Assay established that this FDA-approved IVD assay can accurately identify key companion diagnostic targets," said Helen Fernandes, Ph.D., Professor of Pathology at Columbia University Medical Center. "These findings are important, as they enable clinicians to confidently use results from the oncoReveal Dx test to inform therapeutic decisions, helping patients begin their treatment journey with confidence that their physician has selected the appropriate treatment for the specific cancer."

The validation study was conducted using various DNA input amounts between 5-160ng, from Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissues. Results demonstrate that oncoReveal Dx detects clinically significant variants (KRAS G12/G13, EGFR L858 and exon 19 deletion, and BRAF V600E) from as low as 10ng of DNA input with LoD between 1.5% and 2.6% (VAF, Variant Allele Frequency). In addition, across 263 clinical samples, positive percent agreement (PPA) and negative percent agreement (NPA) between oncoReveal Dx and an externally validated comparator were >99% each. For reproducibility, the average percent positive agreement (APA) and average percent negative agreement (ANA) were each >95%. These results show that oncoReveal Dx is highly accurate for the detection of clinically relevant variants and specification of associated approved therapy, and can accurately identify key companion diagnostic targets within KRAS and EGFR genes, as well as additional variants outside the companion diagnostic targeted list.

"The collective data presented at AACR (Free AACR Whitepaper) adds to the robust body of evidence supporting the accuracy and efficiency of Pillar’s suite of diagnostic testing solutions," said Randy Pritchard, CEO of Pillar Biosciences. "We believe that by decentralizing NGS testing and providing physicians with actionable, highly accurate genetic data in as little as 48 hours, we can significantly optimize selection of precision therapies to treat various cancers. We are pleased to share these data with the industry and to continue developing our NGS test portfolio in order to help make the selection of an appropriate therapy a more efficient process for the oncology community."

Three additional posters were presented at AACR (Free AACR Whitepaper). These studies were designed to support the technology of Pillar’s NGS testing platform. In a poster entitled "Single tube PCR-based NGS assay for detection of multiple gene fusions from cell free total nucleic acid", results demonstrated that Pillar’s single tube assay successfully detected fusion from cfRNA down to 0.5% VAF, and had over 99% sensitivity and specificity down to 4% VAF with as low as 10ng of DNA input. In the poster entitled, "Accurate detection of microsatellite instability (MSI) in matched and unmatched clinical tumor samples using the Pillar oncoReveal MSI panel", investigators evaluated the oncoReveal MSI Panel’s accuracy in the detection of tumor microsatellite instability (MSI) status without a matched normal tissue comparator, and found that results were comparable to the normal matched tissue context. The company also presented data on the accurate detection of tumor sequence of low tumor content samples in MRD monitoring, in a study entitled, "Accurate detection of tumor sequence at low tumor content for MRD".

The four posters are available in the "Posters" section of the company’s website at www.pillar-biosciences.com/our-presence/.

Poster Presentation Details

Abstract 5795: Validation of FDA approved oncoReveal Dx lung and colon cancer assay (oRDx-LCCA)
Date/Time: Friday, April 8, 2022, 12:00 PM – 1:00 PM ET
Session: Genomics
Session Type: E-Poster Session
Presenter: Gloria Chan Johnson

Abstract 5996: Single tube PCR-based NGS assay for detection of multiple gene fusions from cell free total nucleic acid
Date/Time: Friday, April 8, 2022, 12:00 PM – 1:00 PM ET
Session: Metastasis
Session Type: E-Poster Session
Presenter: Tejashree Modak

Abstract 5694: Accurate detection of microsatellite instability (MSI) in matched and unmatched clinical tumor samples using the Pillar oncoReveal MSI panel
Date/Time: Friday, April 8, 2022, 12:00 PM – 1:00 PM ET
Session: DNA Damage and Repair
Session Type: E-Poster Session
Presenter: Jordan Aldersley

Abstract 5066: Accurate detection of tumor sequence at low tumor content for MRD
Date/Time: Friday, April 8, 2022, 12:00 PM – 1:00 PM ET
Session: Convergence Science and Systems Biology
Session Type: E-Poster Session
Presenter: Andrew Conley

On April 11, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported the randomization of the 300th patient and thus the successful completion of patient recruitment in its phase III clinical trial COMPETE, evaluating the efficacy and safety of its lead Targeted Radionuclide Therapy candidate, ITM-11 (n.c.a. 177Lu-edotreotide), in grade 1 and 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (Press release, ITM Isotopen Technologien Munchen, APR 11, 2022, View Source [SID1234611989]). Completing patient recruitment is an important milestone demonstrating the progress of the COMPETE study, with which ITM aims to prove the potential of its therapeutic approach to provide added value to patients with GEP-NETs by improving both, treatment outcomes and the patient’s quality of life.

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GEP-NETs are rare types of tumors originating in the pancreas or other parts of the gastrointestinal tract. Due to their heterogeneity and unique characteristics, diagnosing GEP-NETs early is difficult, increasing the likelihood of metastatic disease and severely limiting treatment options. With ITM-11, the company is striving to address the existing unmet need, providing patients options with an effective approach to treating these life-threatening tumors. This goal is supported by results from previous studies and compassionate use, which suggest a high potential for this therapeutic approach. To further broaden its reach, ITM-11 is also being evaluated in a second phase III trial, COMPOSE, for patients with high grade 2 and grade 3 GEP-NETs.

"Targeted Radionuclide Therapy with ITM-11, may provide an effective and well tolerated treatment option for patients with GEP-NETs, who have a high unmet medical need. This highly targeted, precise approach minimizes radiation exposure of surrounding healthy tissue and helps to maintain quality of life during treatment," commented Prof. Jaume Capdevila, Principal Investigator of COMPETE at the University Hospital Vall d’Hebron in Barcelona, Spain. "We look forward to collecting further data from the study and evaluating ITM-11 in this large patient population."

"This is a very important step forward for ITM as our lead candidate continues through the final stages of the clinical trial," added Steffen Schuster, CEO of ITM. "Completing patient recruitment for COMPETE underscores the progress of our broad proprietary pipeline of radiopharmaceuticals which we hope will improve the lives of patients living with solid tumors and severely limited treatment options such as GEP-NETs. With our research and clinical studies, we strive to meet the needs of a patient population that could benefit from precision oncology treatments."

COMPETE (NCT03049189) is an international, prospective, randomized, controlled, open-label, multi-center phase III study to evaluate the efficacy and safety, of Targeted Radionuclide Therapy with ITM-11 (n.c.a. 177Lu-edotreotide) compared to targeted molecular therapy with everolimus in patients with inoperable, progressive, grade 1 and 2, somatostatin receptor-positive (SSTR+) neuroendocrine tumors of gastroenteric or pancreatic origin. The study has randomized 300 patients across multiple participating study sites worldwide. The primary endpoint of the study is progression-free survival (PFS), and secondary outcome measures include overall survival (OS).

The COMPETE study design was presented at the AACR (Free AACR Whitepaper) annual meeting 2021. ITM’s second phase III trial with ITM-11 for grade 2 and 3 GEP-NETs, COMPOSE (NCT04919226), is ongoing and was introduced at the 2021 North American Neuroendocrine Society (NANETS) symposium as well as at the 2022 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI). Sponsor of both studies is ITM’s subsidiary ITM Solucin GmbH.

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule (e.g., peptide, antibody, small molecule) that can precisely recognize tumor cells and bind to tumor-specific characteristics, such as receptors on the tumor cell surface. As a result, the radioisotope accumulates at the tumor site and decays, releasing a small amount of ionizing radiation, thereby destroying tumor tissue. The highly precise localization enables targeted treatment with minimal impact to healthy surrounding tissue.

About ITM-11 (n.c.a. 177Lu-edotreotide)

ITM-11, ITM’s therapeutic radiopharmaceutical candidate being investigated in the phase III clinical studies COMPETE and COMPOSE, consists of two components: the medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu) and the targeting molecule edotreotide, a synthetic form of the peptide hormone somatostatin that targets neuroendocrine tumor-specific receptors. Edotreotide binds to these receptors and places the medical radioisotope n.c.a. lutetium-177 directly onto the diseased neuroendocrine cells so that it accumulates at the tumor site. N.c.a. lutetium-177 is internalized into the tumor cells and decays, releasing medical radiation (ionizing β-radiation) with a maximum radius of 1.7 mm and destroying tumor tissue. The highly precise localization can result in the healthy tissue surrounding the targeted tumor being minimally affected.

On April 11, 2022 Circle Pharma, a pre-clinical stage company focused on developing macrocycle therapeutics against targets previously considered to be undruggable, reported that it will present a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 8-13, in New Orleans, Louisiana (Press release, Circle Pharma, APR 11, 2022, View Source [SID1234611987]).

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The Company’s presentation will provide details of its progress towards structure-guided macrocycles that inhibit the protein-protein interaction between the cyclin A:CDK2 complex and key substrates that are phosphorylated by this complex. Inhibition of Cyclin A substrate binding has been postulated to be synthetic lethal in Rb mutated cancers. The data presented include evidence that macrocycle inhibitors of cyclin A induce G2/M arrest and apoptosis in small cell lung cancer (SCLC) cell lines and have anti-tumor efficacy in SCLC xenograft animal models. Circle plans to advance its cyclin A inhibitor program to the clinic for testing in a range of cancer types, including SCLC where Rb mutations are highly prevalent.

The presentation will be made as part of the Mechanisms of Drug Action / Experimental and Molecular Therapeutics session at the AACR (Free AACR Whitepaper) meeting, Abstract No. 5379.

On April 11, 2022 CytoImmune Therapeutics, a clinical-stage immunotherapy company developing a novel class of natural killer (NK) cell-based cancer therapies, reported new preclinical data supporting the therapeutic potential of its CYTO-102 and CYTO-201 programs as treatments for patients with cancer (Press release, CytoImmune Therapeutics, APR 11, 2022, View Source [SID1234611986]). New findings demonstrate the utility of its NK cell platform to generate off-the-shelf, tumor-reactive NK cell (TRACK-NK) and chimeric antigen receptor (CAR) engineered NK cell (CAR-NK) therapies, that result in effective tumor cell killing with favorable tolerability for both solid and liquid tumors. The data are being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 8-13, 2022, in New Orleans.

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CytoImunne’s unique approach aims to engineer NK cells into therapies that can both directly kill cancer cells, while also broadly stimulating the body’s own endogenous immune system to drive cancer cell death. The company is developing two co-lead NK cell therapies: (1) CYTO-102, a TRACK-NK cell therapy engineered to secrete high levels of soluble IL-15 being developed for the treatment of non-small cell lung cancer (NSCLC) and (2) CYTO-202, a FLT3-directed TRACK-CAR-NK cell therapy that the company is developing for the treatment of acute myeloid leukemia (AML).

"We are very excited to present these new data from two of our proprietary NK cell-based programs, both of which have demonstrated meaningful potential in addressing challenging to treat cancers, including NSCLC and AML," said Michael Caligiuri, MD co-founder and chief scientific officer. "For cancers such as NSCLC, we’ve seen advancements in the field with the emergence of checkpoint inhibitors, but the disease remains incredibly difficult to treat and a major cause of cancer-related mortality worldwide. With our TRACK-NK cells, we believe we may be able to enhance tumor destruction in patients, leading to improved and durable outcomes."

Christina Coughlin, chief executive officer, added "For aggressive cancers like AML, we believe there are certain advantages that an off-the-shelf targeted cell therapy could offer patients compared to autologous CAR T cell therapy, which has a long preparation time – a challenging approach in the face of such a fast-progressing disease. Taken together, findings from our preclinical research validate our novel approach to leveraging NK cells to create treatments for both solid and liquid tumors and support their continued advancement toward the clinic."

Abstract Title: LB211. Tumor-reactive and anti-PD-L1 co-stimulated killer cells (TRACK-NK) for immunotherapy of non-small cell lung cancer
Session: Late-Breaking Research: Immunology 2
Session Date & Time: Wednesday, April 13, 2022, from 9:00 a.m. to 12:30 p.m. ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 18
Summary of Findings: CytoImmune is advancing its CYTO-102 program, an anti-PD-L1 co-stimulated TRACK-NK therapy for the potential treatment of non-small cell lung cancer (NSCLC). The novel therapy was generated by genetically modifying NK cells to express soluble IL-15 (sIL15), an immune signaling molecule crucial for optimal antitumor response and primed with cytokines IL-12 and IL-18 to induce PD-L1 expression. In vitro and in vivo evaluation of the TRACK-NK cells showed:

Following cryopreservation, thawed sIL15-PDL1 NK (TRACK-NK) cell product demonstrated high recovery and viability
Significant cytotoxicity against a human NSCLC cell line when compared to NK cells without expression of sIL-15, NK cells without expression PD-L1, or NK cells without expression of both
Repeated infusions of human TRACK-NK cells resulted in a significant tumor suppression compared to cells only expressing sIL15, PD-L1 or neither of both, in a mouse model
Treatment was well tolerated in mice, with no changes in bodyweight or body temperature and no significant changes in liver and kidney functions observed
Abstract Title: LB102. Off-the-shelf cord blood FLT3 CAR-NK cells for immunotherapy of acute myeloid leukemia
Session: Late-Breaking Research: Immunology 1
Session Date & Time: Monday, April 11, 2022, from 1:30 p.m. to 5:00 p.m. ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 18
Summary of Findings: CytoImmune’s CYTO-201 product candidate is a novel, off-the-shelf CAR-NK cell therapy designed to express a specific anti-FLT3-CAR with a secretory soluble form of IL-15. CYTO NK-201 is being investigated as a potential treatment for acute myeloid leukemia (AML), an aggressive hematologic malignancy in which FLT3 expression is present on approximately 20-30% of patients. In vitro and in vivo evaluation of the company’s FLT3 CAR NK cells showed:

Enhanced cytotoxicity in FLT-3 positive human AML cells
Reduced tumor burden and prolonged survival in an aggressive AML mouse model when compared to cells only expressing IL-15 or to the control group
Good tolerability with no signs of toxicity against normal hematopoietic stem cells that also express the FLT-3 marker

On April 11, 2022 MiNA Therapeutics Limited ("MiNA" or the "Company"), the pioneer in small activating RNA (RNAa) therapeutics, reported that preclinical proof of mechanism data on MTL‑STING as a novel cancer immunotherapy (Press release, MiNA Therapeutics, APR 11, 2022, View Source [SID1234611985]). The data validates the drug candidate’s ability to upregulate the STING protein and related downstream pathways of innate immunity through gene activation. The data was presented at a poster session on 10 April 2022 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s (AACR) (Free AACR Whitepaper) annual meeting in New Orleans, entitled ‘MTL-STING restores endogenous STING expression for improving efficacy of cancer therapeutics.’

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Robert Habib, CEO of MiNA Therapeutics, commented:

"We are very pleased to present this encouraging data and to advance MTL-STING further in development. It is the second drug candidate in our internal pipeline of RNAa therapeutics. Upregulation of the STING protein is a radically new approach to improving the innate immune response in cancer patients and enhancing the effectiveness of existing anti-cancer therapies. Demonstrating that MTL‑STING can increase levels of STING protein and activate downstream innate immune pathways is a major step towards this goal, and in expanding the possibilities of RNAa therapeutics."

STING (stimulator of interferon genes) is a master regulatory protein that is essential for identification of cancer cells by the immune system. Downregulation of STING has been reported as a key immune-evasion mechanism in cancer patients and a root cause of inactivation of the cGAS-cGAMP-STING pathway of innate immune response.

Upregulating STING presents a novel therapeutic approach to address immune evasion and improve the effectiveness of existing immunotherapies in cancer patients. To date, therapeutics seeking to drug the cGAS-cGAMP-STING pathway have provided limited benefit to cancer patients. Largely small molecule agonists, they have failed to address the underlying downregulation of STING itself and, in addition, have been limited by safety and bioavailability.

The preclinical data presented at AACR (Free AACR Whitepaper) demonstrated that MTL‑STING upregulated STING mRNA production by more than fivefold, consistent with the activity required to restore STING to homeostatic levels in cancer patients. Importantly, upregulation of STING mRNA was durable, leading to increased levels of STING protein and downstream functional activation of innate immune pathways. MTL-STING is initially being developed as a combination treatment for solid tumour malignancies, with the expectation to enter Phase 1 evaluation in 2023.

MTL‑STING is the second drug candidate to be advanced from MiNA’s internal pipeline of RNAa therapeutics. MiNA’s first drug candidate, MTL-CEBPA, is currently being evaluated in a global Phase 2 clinical trial in combination with sorafenib in advanced hepatocellular carcinoma (HCC or liver cancer). RNAa therapeutics are a revolutionary new class of medicines that can restore or boost normal function within patients’ cells by selectively activating genes.

The poster presented at AACR (Free AACR Whitepaper) will be made available on the Company’s website at View Source