On June 28, 2021 The National Cancer Institute reported that it has awarded the Lung Cancer Metabolism Working Group at Moffitt Cancer Center with a Research Program Project Grant (P01CA250984) (Press release, Moffitt Cancer Ctr, JUN 28, 2021, View Source [SID1234584400]). The grant, which will provide more than $10.2 million over five years, will support team research across several Moffitt programs, including Cancer Biology and Evolution, Molecular Medicine and Immuno-Oncology. All projects will focus on investigating lung cancer metabolism.

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Moffitt’s program project consists of four projects and four shared cores. The goal is to unveil common metabolic mechanisms regulated by common genetic drivers across non-small cell lung cancer, specifically lung adenocarcinoma and squamous cell carcinoma, and small cell lung cancer. Researchers will then use that information to utilize standard of care therapeutics or develop new therapies that can target the common molecular signatures.

"Many of the driver genes mutated in lung cancer, like p53, Nrf2 and myc, are transcription factors, which are difficult to target therapeutically and have been deemed ‘undruggable.’ But by learning more about the cancer metabolism and how malignant cells are rewiring their metabolic network to survive, we can develop novel therapies to target those rewired cells while preserving the integrity of normal surrounding tissues," said Elsa Flores, Ph.D., principal investigator for this grant, chair of the Department of Molecular Oncology and leader of the Cancer Biology and Evolution Program.

Lung cancer is the leading cause of cancer deaths worldwide. There are two types of lung cancer: non-small cell lung cancer, which accounts for roughly 80% to 85% of cases, and small cell lung cancer, which has been classified by the NCI as a recalcitrant tumor – a type of cancer with a five-year relative survival rate of less than 50%.

Common therapy for both lung cancer types includes surgery, radiation, chemotherapy and immunotherapy. These treatments can be debilitating for patients, and for those treated with chemotherapy and/or radiation, healthy surrounding tissue can be harmed. Although immunotherapy has improved lung cancer outcomes, it only works for a small subset of patients.

"We see about 1,800 new lung cancer patients each year in our thoracic clinic. We are seeing what works and what doesn’t. We know improvements can be made to appropriately apply standard of care treatments and even develop new, more targeted therapies, but first we need to further our understanding of the basic biology of lung cancer disease progression. These four projects will help our team do just that," said Eric Haura, M.D., co-principal investigator of the grant, associate center director of Clinical Science and director of the Lung Cancer Center of Excellence.

Preliminary data for this project was supported by Moffitt’s Lung Cancer Center of Excellence and Miles for Moffitt.

On June 28, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing onvansertib to treat cancers with the greatest medical needs for new treatment options, including KRAS-mutated colorectal cancer, pancreatic and castrate-resistant prostate cancer, reported that it has been added as a member of the small-cap Russell 2000 Index, the all-cap Russell 3000 Index, and the Russell Microcap Index, effective upon the U.S. market open today, June 28, 2021, as part of the 2021 Russell indexes reconstitution (Press release, Cardiff Oncology, JUN 28, 2021, View Source [SID1234584416]).

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The 2021 annual reconstitution of the Russell indexes captured the 4,000 largest U.S. stocks as of May 7, 2021, ranking them by total market capitalization. Membership in the U.S. all-cap Russell 3000 Index, which remains in place for one year, means automatic inclusion in the large-cap Russell 1000 Index or small-cap Russell 2000 Index as well as the appropriate growth and value style indexes. FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings and style attributes.

Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $10.6 trillion in assets are benchmarked against Russell’s U.S. indexes. Russell indexes are part of FTSE Russell, a leading global index provider. For more information on the Russell 3000, Russell 2000 and Russell Microcap Indexes and the Russell indexes reconstitution, go to the "Russell Reconstitution" section on the FTSE Russell website.

On June 28, 2021 Heat Biologics, Inc. (Nasdaq: HTBX), a clinical-stage biopharmaceutical company focused on developing first-in-class therapies to modulate the immune system, reported that it has been added to the Russell Microcap Index, following the annual Russell indexes reconstitution, effective after the US market opens today, June 28, 2021, according to a final list of additions posted on June 25, 2021 (Press release, Heat Biologics, JUN 28, 2021, View Source [SID1234584401]).

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Membership in the Russell Microcap Index, which remains in place for one year, means automatic inclusion in Russell’s appropriate growth and value style indexes. FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings, and style attributes.

Jeff Wolf, Chief Executive Officer of Heat, commented, "We are extremely pleased to join the Russell Microcap Index and believe that our inclusion will increase our visibility and exposure to investors. Joining this index is a reflection of the progress we have made this year in our clinical programs, including both our oncology program and COVID-19 vaccine program, building a strong balance sheet with over $132 million of cash and short-term investments as of Q1 2021 and increasing shareholder value."

Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $10.6 trillion in assets are benchmarked against Russell’s US indexes. Russell indexes are part of FTSE Russell, a leading global index provider. For more information on the Russell Microcap Index and the Russell indexes reconstitution, go to the "Russell Reconstitution" section on the FTSE Russell website.

On June 28, 2021 MaaT Pharma, a clinical-stage biotechnology company focused on developing Microbiome Ecosystem Therapies in oncology, reported that the Data Safety and Monitoring Board (DSMB) recommended to proceed to the fourth cohort of the dose-finding Phase 1b CIMON clinical trial, without modifications (Press release, MaaT Pharma, JUN 28, 2021, View Source [SID1234584417]). The DSMB is an independent committee monitoring the progress of the company’s clinical trial and is reviewing safety, tolerability and data quality while the trial is ongoing.

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"We are very pleased that the third of five cohorts in this important study with MaaT033 has successfully been completed without any safety signals reported. This is a very meaningful step towards determining the target dose of this oral capsule product candidate, and we expect to initiate a pivotal Phase 3 study next year," commented John Weinberg, MD, Chief Medical Officer at MaaT Pharma.

The CIMON trial (NCT04150393) is enrolling a total of 27 patients at 6 sites across France. It is an open-label Phase 1b study to investigate the maximum tolerated dose of MaaT033, over 7 or 14 days of therapy, that supports optimal gut microbiome colonization in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome who have undergone intensive chemotherapy.

The CIMON Phase 1b trial is expected to be completed at the end of 2021.

About MaaT033

MaaT033 is an oral, full-ecosystem, off-the-shelf, standardized, pooled-donor, high-richness microbiome biotherapeutic. It is manufactured at MaaT Pharma’s centralized European cGMP production facility. MaaT033 is designed to restore the gut ecosystem to full functionality to improve clinical outcomes as well as to control adverse events related to conventional treatments for liquid tumors. The capsule formulation facilitates administration while maintaining the high and consistent richness and diversity of microbial species, including anti-inflammatory "Butycore" species, which characterize MaaT Pharma’s Microbiome Ecosystem Therapies.

On June 28, 2021 ImmunityBio, Inc., a publicly traded immunotherapy company, and privately-held NantOmics reported publication of a stepwise approach or "pipeline" for identification and validation of neoepitope and neoepitope-reactive T cells from individual patients (Press release, ImmunityBio, JUN 28, 2021, View Source [SID1234584402]). The identification of neoepitopes—short peptide sequences that are mutated in tumors and are capable of generating an immune response—provides critical support in the successful development of next-generation immunotherapies delivered by ImmunityBio’s Adeno- and yeast-based platforms. The pipeline is described in "Identification and validation of expressed HLA-binding breast cancer neoepitopes for potential use in individualized cancer therapy," which recently published in the Journal for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).

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The pipeline leverages the bioinformatics capabilities of NantOmics and ImmunityBio to predict neoepitopes based on genomic and expression analyses that have a high likelihood of generating a tumor-fighting immune response and the generation of neoepitope-specific CD4+ and CD8+ T cells when delivered using the Adeno and yeast vaccine platforms. These predicted neoepitopes once identified are synthesized as short peptides, and run through a series of studies to confirm their potential utility in the cancer vaccine platforms. The pipeline was developed in conjunction with physicians and scientists at Friedrich Alexander University in Germany and the National Cancer Institute (NCI) in the U.S.

In clinical use, this neoepitope discovery system supports the targeted delivery of antigens with ImmunityBio’s second-generation Adeno platform. This platform, which has shown promising results in Phase 1 and 2 trials, activates CD4+ and CD8+ T cells after delivery of tumor-associated antigens in patients with advanced solid tumors and colon cancer. In preclinical studies conducted in collaboration with the NCI, accurate prediction of neoepitopes, delivered via the adenovirus platform, resulted in complete response in colon cancer when combined with ImmunityBio’s IL-15 superagonist Anktiva and other immune-based therapies. That study highlights the potential for neoepitope identification to inform highly effective anti-tumor therapy.

"The future of immunotherapy is in a personalized approach," said Dr. Patrick Soon-Shiong, Founder and Executive Chairman of ImmunityBio. "By tailoring therapies to the individual biology of each patient’s cancer, we greatly increase the likelihood of successful treatment using our ever-increasing arsenal of immune-based therapies."

"Validation of the neoepitope identification pipeline in actual patients from the TILGen study was an important aspect of the proposed method," said Dr. Peter Fasching, who with Dr. Anita Kremer, was senior author on the manuscript. "We were able to isolate the specific immune cells that recognized the predicted neoepitopes. Those immune cells aimed at the cancer cells’ neoepitopes are very important because they could potentially kill a tumor. Clinically, the predicted and confirmed neoepitopes could be targeted by vaccines or adoptive cell transfer therapies and improve patient outcomes."

Neoepitopes can be unique for each patient and when the pipeline is applied, the analyses for identification of these neoepitopes would be performed using tumor and other tissues collected from individual patients.

This method for identifying tumor-specific immunogenic targets for individualized treatment can be used as part of a program including other immune and cell-based therapies available through ImmunityBio, including CAR T-cell therapies and vaccines. Efficacy of these therapies could be further enhanced by combination with an immune enhancer such as ImmunityBio’s Anktiva or Natural Killer (NK) cells.

About the Neoepitope Identification Pipeline

The bioinformatics methodology, well-established at NantOmics, readily and accurately predicts neoantigens;
Practical cell-based assays of synthesized neoepitope peptides refines candidates to those most likely to induce an immune response;
and Tissues and cells routinely collected from individual cancer patients can be used to confirm and further narrow neoepitope candidates.
The neoepitope identification and validation pipeline is feasible, practical and accurate, as this first report suggests. It is anticipated that it will be applied in future clinical studies of immunotherapies to determine the merits of this personalized approach to precision medicine for cancer.