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).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 Clovis Oncology, Inc. (NASDAQ: CLVS), reported that Professor Dr. Richard P. Baum and Dr. Harshad R. Kulkarni, in conjunction with 3B Pharmaceuticals (Clovis’ licensing partner and discoverer of FAP-2286), published a retrospective report of their independent experience with FAP-2286 in named-patient use in The Journal of Nuclear Medicine (Press release, Clovis Oncology, JUN 28, 2021, View Source [SID1234584399]). In the first named-patient experience of the investigational compound conducted at Zentralklinik, Bad Berka, Germany, patients were treated with the FAP-targeted radiotherapy FAP-2286 linked to the radionuclide lutetium-177 (177Lu) as a therapeutic agent after prior confirmation of tumor FAP-positivity in patients by PET/CT imaging.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In this palliative use setting, FAP-2286 was administered on a named-patient basis to 11 patients with progressive and metastatic adenocarcinoma of the pancreas, breast, rectum, and ovary after prior confirmation of FAP expression. According to the authors, administration of 177Lu-FAP-2286 demonstrated high uptake and long retention in primary and metastatic tumor lesions and an acceptable toxicity profile. The report concludes that the data warrant further investigation of 177Lu-FAP-2286 in clinical studies to systematically evaluate its safety and efficacy, and to define the patient population who would benefit most from treatment.

The Clovis Oncology-sponsored Phase 1/2 LuMIERE study of 177Lu-FAP-2286 is evaluating the compound in patients with advanced solid tumors. FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients appropriate for treatment in LuMIERE.

"We believe the early clinical experience from named-patient use validates our plans to further investigate FAP-2286 as a therapeutic and imaging agent across a variety of solid tumor types," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We are very pleased to move FAP-2286 into formal clinical development with the recent initiation of the Phase 1/2 LuMIERE study of FAP-2286, a novel peptide-targeted radionuclide therapy in patients with solid tumors."

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas. Clovis holds U.S. and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

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 delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis, together with licensing partner 3B Pharmaceuticals, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

About the LuMIERE Clinical Study

LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a peptide-targeted radionuclide therapy (PTRT) targeting fibroblast activation protein, or FAP, in patients with advanced solid tumors. The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

On June 28, 2021 Polyphor AG (SIX: POLN), a research driven clinical stage, Swiss biopharmaceutical company committed to discovering and developing best-in-class molecules in oncology and antimicrobial resistance reported that its global Phase III study, FORTRESS, evaluating balixafortide (POL6326) in combination with eribulin for the treatment of patients with HER2 negative, locally recurrent or metastatic breast cancer, did not meet its co-primary endpoint (Press release, Polyphor, JUN 28, 2021, View Source [SID1234584398]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At the primary analysis, balixafortide plus eribulin showed no improvement in the objective response rate (ORR) compared with eribulin alone (13.0% versus 13.7%; p=1.00) in the third line and later population (n=330 patients) followed for a minimum of 6 months. The clinical benefit rate, a key secondary endpoint indicating a stable disease or any confirmed response for a duration of at least 6 months as assessed by the IRC (independent radiological committee) was observed in 16.7% of patients in the balixafortide plus eribulin arm and 19.6% in the eribulin alone arm. The study confirmed the positive safety and tolerability profile of balixafortide in line with the previously reported Phase Ib study. Polyphor will continue to analyze the data, review with the experts and will decide about the future of the study in mid-July.

The board of directors is undergoing a strategic assessment and will consider a full range of options regarding the future of the company and will provide an update not later than end of July.

"Given the high unmet medical need for patients with HER2 negative breast cancer in a late stage of the disease, we are disappointed that the FORTRESS study did not meet its coprimary endpoint," says Gökhan Batur, CEO of Polyphor. "We thank all the patients, investigators and healthcare professionals as well as our employees for their active participation in this study."

About the FORTRESS study

The FORTRESS study (POL6326-009) is an international, multicenter, randomized active-controlled, open-label Phase III trial which investigates the efficacy, safety and tolerability of intravenous balixafortide given with eribulin versus eribulin alone in the treatment of HER2 negative, locally recurrent or metastatic breast cancer. The study had randomized 432 patients with HER2 negative MBC with at least 344 patients receiving third or subsequent line and 88 patients receiving second line chemotherapy.

About balixafortide

Balixafortide (POL6326) is a potent, specific, and highly selective antagonist of the chemokine receptor CXCR4, a G-protein coupled receptor (GPCR) that regulates the trafficking and homing of both cancer cells and cells of the patient’s immune system.