On October 3, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA), a clinical stage company developing telomere-targeting immunotherapies for cancer, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for THIO to be evaluated in the U.S. as part of THIO-101, the Company’s ongoing global phase 2 clinical study in patients with advanced Non-Small Cell Lung Cancer (NSCLC) (Press release, MAIA Biotechnology, OCT 3, 2023, View Source [SID1234635616]). THIO is being tested in sequential combination with Regeneron’s anti PD-1 monoclonal antibody cemiplimab (Libtayo) to evaluate anti-tumor activity and immune response in NSCLC patients.

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"We are extremely pleased to obtain clearance to extend our go-to-market THIO-101 trial to the U.S. and further develop THIO’s global reach," said Vlad Vitoc, MAIA’s Chief Executive Officer.

"The FDA IND clearance represents an essential milestone in the clinical development of THIO, as a first-in-class telomere targeting agent in clinical development for patients with advanced NSCLC," said Mihail Obrocea, M.D., MAIA’s Chief Medical Officer.

"We worked diligently with the FDA throughout the pre-IND/IND process to successfully align with their regulatory guidance and recommendations and we remain committed to developing novel, safe and effective treatments for patients with cancer," added K. Robinson Lewis, MAIA’s Head of Regulatory and Quality.

About Investigational New Drug Application

An Investigational New Drug (IND) application is a request for authorization from the U.S. Food and Drug Administration to administer an investigational drug or biological product to humans in the United States. Organizations can initiate a clinical trial in the U.S. with IND clearance from the FDA.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About THIO-101, Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to Regeneron’s anti-PD1 cemiplimab (Libtayo) will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator and (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

On October 3, 2023 BostonGene, a leading provider of AI-based molecular and immune profiling solutions, reported a master agreement with Johns Hopkins University School of Medicine (JHUSOM) to collaborate on multiple clinical research projects (Press release, BostonGene, OCT 3, 2023, View Source [SID1234635615]). The agreement allows BostonGene and JHUSOM to further identify and validate novel precision medicine approaches.

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JHUSOM will work with BostonGene on the molecular characterization study of the patient’s tumor, microenvironment and immune system and its predictive value in response to treatment. BostonGene’s solution will provide JHUSOM with detailed analysis, interpretation and visualization of big data obtained from cancer patient’s genomic, transcriptomic, proteomic and imaging studies. This work hopes to identify significant somatic alterations, evaluate protein expression, compute tumor clonality, tumor heterogeneity, tumor microenvironment cell type composition, hereditary predisposition, viral infestation and pharmacogenomics and predict neoantigens for personalized vaccine development, among other molecular features. BostonGene will perform comprehensive bioinformatics to validate hypothesis-driven research to identify targetable molecular alterations.

"We’re honored to collaborate with JHUSOM to provide our AI-based molecular and immune profiling techniques that comprehensively analyze the tumor, microenvironment, and immune system to uncover treatable targets to personalize therapy for patients," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. "This collaboration supports our mission to support doctors in finding the most effective strategy for personalized treatment options for their patients."

On October 3, 2023 Olatec Therapeutics LLC (Olatec), a leader in the developing class of oral selective NLRP3 inhibitors, reported a publication in Cancer Research Communications showing a reduction in tumor progression with dapansutrile as a monotherapy, resulting from inhibition of NLRP3/IL-1β pathway in mouse models of pancreatic ductal adenocarcinoma (PDAC) (Press release, Olatec Therapeutics, OCT 3, 2023, View Source [SID1234635614]). Additionally, the data show that dapansutrile, when administered in combination therapy with gemcitabine significantly increased efficacy of this chemotherapy.

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PDAC has been reported to constitute ninety percent of all pancreatic cancers and it is the third leading cause of cancer deaths in the US and seventh worldwide. Long-term survival among PDAC patients remains poor due to a lack of effective screening methods, nonspecific symptoms, and limited treatment options. While there has been improvement in systemic chemotherapy, an urgent need still exists for an effective treatment.

Inflammation in the tumor microenvironment (TME) in PDAC models caused by activation of the IL-1β pathway has been shown to promote PDAC cell proliferation, metastasis and to limit response to chemotherapy. Olatec’s preclinical studies advance this understanding by demonstrating that NLRP3 participates in the IL‑1β-mediated PDAC progression. Dr. Carlo Marchetti, the investigator in these studies, shows NLRP3 to be highly expressed in the tissue of pancreatic tumors when compared to normal pancreatic tissue. Dr. Marchetti further demonstrates that PDAC-bearing wild type mice treated with dapansutrile significantly reduce tumor growth and mass, which was confirmatory in his studies using mice with the NLRP3 genetic deletion. Advancing Olatec’s understanding of dapansutrile’s immunologic effect in cancer, the studies also show that inhibition of NLRP3 with dapansutrile result in intra-tumoral increase in IL-2, a reduction in T-helper (Th)2 response, and an augmented activation of CD8 T cells which resulted in a favorable change in the T Cell phenotype of the TME.

When asked about the implications of these findings, Charles Dinarello MD, Olatec SAB Chair, said: "the preclinical data we have generated using a well-established murine model of PDAC provide the rationale to advance dapansutrile into a PDAC clinical trial."

Olatec’s Founder and CEO, Damaris Skouras, commented: "There is an urgent unmet need for an effective treatment to extend patient survival with this pernicious form of pancreatic cancer. We believe patient outcomes could potentially be improved if the data from our preclinical studies translate in clinic trials."

About Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma has been reported to constitute 90% of all pancreatic cancers and it is the third leading cause of cancer deaths in the US and seventh worldwide. The incidence rate for pancreatic cancer has increased by about 1% per year since the late 1990s in both men and women, according to American Cancer Society (Cancer Facts & Figures 2023). Lack of effective screening methods, nonspecific symptoms and limited treatment options are major limitations in the management of this disease that contribute to the extremely severe prognosis in pancreatic cancer patients. The 5-year survival reached approximately 11% for the first time in 2022. A combination of systemic therapy and surgery is needed to treat patients with PDAC in order to achieve the best chance at long-term outcomes. While there has been improvement in systemic chemotherapy, long-term survival among PDAC patients remains poor. Immunotherapy has increasingly become a treatment option of interest for many cancer types. The efficacy of immunotherapy to treat PDAC patients remains unclear, however, the PDAC tumor microenvironment may promote resistance to immunotherapy supporting the rationale for intervention with anti-inflammatory therapies.

About Dapansutrile

Dapansutrile (lab code: OLT1177) is an investigational small molecule, new chemical entity that specifically binds to and blocks NLRP3 (nucleotide-binding and oligomerization domain [NOD]‑, leucine rich repeat-, pyrin domain-containing 3), the sensor molecule integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of bioactive IL-1β and IL-18 through caspase-1 activation. Dapansutrile has been shown to inhibit the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL-1β and IL‑18. NLRP3 is one of the most characterized inflammasome sensors due to its involvement in a wide range of disorders, including sterile inflammation, infections, and rare genetic autoimmune syndromes. Dapansutrile has been well tolerated and shown to improve clinical outcomes in patients with acute gout flare (see The Lancet Rheumatology) and heart failure (see Journal of Cardiovascular Pharmacology). Dapansutrile has also been observed to have anti-inflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models including arthritis, asthma, acute myocardial infarction (AMI), heart failure, contact dermatitis, multiple sclerosis, melanoma, pancreatic and breast cancers, spinal cord injury (SCI), Parkinson’s and Alzheimer’s disease. For a complete list of Olatec’s original publications on dapansutrile in various preclinical and clinical disease areas, please refer to Olatec’s publication page, here.

On October 3, 2023 ImmPACT Bio USA, Inc. ("ImmPACT BIO"), a clinical-stage company developing transformative logic-gate-based chimeric antigen receptor (CAR) T-cell therapies for treating cancer and autoimmune diseases, reported that it will participate at the 2023 Cell & Gene Meeting on the Mesa, being held October 10-12, 2023 in Carlsbad, CA (Press release, ImmPACT-Bio, OCT 3, 2023, View Source;gene-meeting-on-the-mesa-301944692.html [SID1234635612]).

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Sumant Ramachandra, M.D., Ph.D., ImmPACT Bio’s president and chief executive officer, will present a corporate update and participate in a Q&A session on Wednesday, October 11, 2023 at 3:15 PM PT.

On October 3, 2023 Menarini Silicon Biosystems, a pioneer of liquid biopsy technology, reported the publication, in the peer-reviewed journal Cancers, of the results of a clinical study on the utility of CTCs to detect disease relapse substantially earlier than what is currently possible with routine surveillance imaging, in patients with stage III melanoma (Press release, Menarini Silicon Biosystems, OCT 3, 2023, View Source [SID1234635611]). This study included 325 patients who were mainly enrolled upon diagnosis of their stage III melanoma status. Blood was collected at different time points to detect CTCs and results were compared with follow-up imaging, to detect disease recurrence. The Menarini Silicon Biosystems CELLSEARCH system and Celltracks Circulating Melanoma Cell Kit* were used to analyze and enumerate CTCs.

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According to Dr. Anthony Lucci, MD, Professor of Surgery in the Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center: "In this study we were able to detect CTCs in over 75% of patients… at a median of nine months prior to a radiological relapse". This data suggests that a blood biomarker is now able to help assess which patients with melanoma are most at risk of experiencing a relapse. "In the future these findings could lead to earlier intervention before a clinical metastasis is formed."

Melanoma is an aggressive cancer with both a propensity to spread to distant sites and poor prognosis when diagnosed at a late stage. Its prevalence has been increasing worldwide[1]. Despite the introduction of new targeted treatments and immunotherapies in the last decade, the risk of relapse continues to represent a major concern. The need, to improve the selection of high-risk patients who can most benefit from new immunotherapies and earlier intervention, is therefore quite urgent.

The overall study cohort was comprised of 174 males (53.5%) and 151 females (46.5%), with a mean age of 54.3 years (range, 20–89 years). CTCs could, in 75% of cases, be identified many months prior to positive radiologic detection of disease relapse. Importantly, CTCs were detected at a median greater than 9 months before the radiological detection of progression, meaning that there is significant lead time available for treatment intervention. Moreover, patients, who had zero CTCs in their blood, were significantly less likely to develop disease relapse compared to those who had a presence of at least 1 CTC (HR: 0.37, 95% CI: 0.26–0.53, p-value < 0.001). This study opens the door to both an earlier detection of disease progression, compared to the current standard of care imaging modalities including PET/CT, MRI, CT or ultrasound, and better timing for the utilization of imaging techniques that are more expensive and represent a higher burden to patients and to the healthcare system. The study results further underline the fact that the CELLSEARCH CTC liquid biopsy test could be used not only to guide earlier intervention but also to regularly monitor patient response to medication.

"We are thrilled by the fact that our CELLSEARCH technology has proven its value to guide early clinical intervention in a disease with a high unmet medical need," said Fabio Piazzalunga, President and CEO of Menarini Silicon Biosystems. "This study is another example of why we are so committed to working with clinical research teams in different oncology settings where our minimally invasive and cost-effective CELLSEARCH platform keeps demonstrating an ability to address unmet healthcare needs".

About stage III melanoma

Stage III melanoma is a form of skin cancer in which cancer cells have spread to the lymph nodes that are located throughout the body. The primary cause of melanoma is exposure to UV radiation from the sun. People with fair skin are more susceptible to developing this disease because they have less melanin, the pigment that gives the skin its color and, also, acts as a UV shield. Because melanoma is the deadliest form of skin cancer with survival rates dropping significantly after metastasis, early diagnosis is key to improve prognosis.

About CELLSEARCH

CELLSEARCH is the first and only clinically validated blood test cleared by the U.S. Food & Drug Administration (FDA) for detecting and counting CTCs to aid physicians in managing patients with metastatic breast, prostate, and colorectal cancers when used in conjunction with other clinical methods of monitoring. The test is also approved by the China National Medical Products Administration (NMPA) for use in monitoring patients with Metastatic Breast Cancer. For more information on the full intended use and limitations of the CELLSEARCH system, please refer to the Instructions for Use at View Source

The Celltracks Circulating Melanoma Cell Kit* immunomagnetically captures CD146-positive cells from whole blood. Circulating melanoma cells are further identified using fluorescently labeled antibodies anti-MEL, anti-CD34, and anti-CD45. Circulating melanoma cells are defined as CD146+, MEL+, CD45-, CD34-.

The Celltracks Circulating Melanoma Cell Kit is available as a Research Use Only product in Europe and Asia Pacific.

In the USA only, the Celltracks Circulating Melanoma Cell test is available to clinicians, through Menarini Silicon Biosystems’ CLIA registered clinical laboratory as a laboratory developed test.