On January 19, 2022 Case Western Reserve University and NeoIndicate LLC have signed an exclusive license agreement to commercialize an imaging agent discovered and developed at the School of Medicine that fluorescently tags tumor cells to guide neurosurgeons to a more precise and complete surgical removal of glioblastoma and other malignant brain tumors (Press release, Case Western Reserve University, JAN 19, 2022, View Source [SID1234605571]).

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In addition, NeoIndicate received a Technology Validation and Start-up Fund (TVSF) Phase 2 award from the State of Ohio to help accelerate the product to market. Specifically, state funding will be used to produce and test the tumor-imaging agent in preparation for a clinical trial.

"We developed a way for clinicians to specifically recognize tumors and created a platform of technologies for use in the detection, imaging and treatment of cancer," said Susann Brady-Kalnay, a professor in the Department of Molecular Biology and Microbiology at the Case Western Reserve School of Medicine, who discovered the biomarker and developed the imaging agents that detect it. She is also NeoIndicate’s founder and chief scientific officer.

Under terms of the agreement, Case Western Reserve, through its Technology Transfer Office (TTO), granted NeoIndicate an exclusive license to the intellectual property rights developed at the university for the imaging agents used to remove the brain tumors.

The technology, called NEO-001, relies on a unique tumor biomarker combined with a fluorescent tag to detect cancerous cells. The biomarker is present on many tumor types in cancer patients, including children, adolescents and young adults.

Andrew Sloan, professor and vice chair of neurosurgery and director of the Brain Tumor and Neuro-Oncology Center at the School of Medicine, as well as the Center for Translational Neuro-Oncology at University Hospitals (UH) Seidman Cancer Center, will conduct the clinical trials. "With advances in intraoperative microscopes, robotic surgical devices and fluorescent dyes, now is the time for tumor-targeted, next-generation fluorescent imaging agents to become standard of care," Sloan said.

"NEO-001 has the potential to transform how clinicians visualize tumors, and our platform of technologies will allow us to monitor treatment efficacy," said NeoIndicate CEO Ted Gastineau.

Gastineau said the company expects to begin patient clinical trials in 2023.

Glioblastoma
The incidence of glioblastoma, the most common brain cancer, is rising and its prognosis remains dismal, with a median survival of 12 to 15 months. Surgical removal of all or part of a tumor—known as resection—remains the first line of treatment, with additional radiation and temozolomide treatment leading to modest improvement in overall survival.

Treatment of brain tumor patients is expensive, often involving ineffective treatments and repeat biopsies. Removing the cancerous tumor tissue while preserving normal tissue in the brain is challenging. Better surgical resection of brain tumors doubles a patient’s survival rate.

However, surgeons can’t always determine the edges of the tumor. And high-grade brain tumors are often invasive, with small tentacle-like projections that extend from the main tumor mass and are invisible to the naked eye.

"It is these tumor cells that lead to greater than 90% recurrence in patients due to tumor cells left at the edge of the primary tumor," Sloan said. "Therefore, better visualization of invading tumor cells improves survival and is an important unmet clinical need."

How the technology works
NeoIndicate’s license gives the company access to a proprietary platform using a unique cell surface adhesion molecule biomarker present only on tumor cells. Brady-Kalnay’s lab developed a series of agents that recognize this unique tumor biomarker.

Using models of various tumor types, she discovered that the targeted agents:

label the main tumor mass within minutes;
bind tumors for hours;
and recognize invasive tumor cells that lead to recurrence.
This technology can be used to recognize cancer cells in applications ranging from diagnosis to imaging along the treatment spectrum, including pre-, during or post-surgery. The agents can also target various treatments to primary, invasive and metastatic tumors to "seek and destroy" cancer.

Additional support
Translational support for Brady-Kalnay’s lab to develop the technology came in part from: the National Institutes of Health, Case Comprehensive Cancer Center, the School of Medicine’s Council to Advance Human Health, Case-Coulter Translational Research Partnership, Ohio Third Frontier and the CWRU TTO.

"We are very excited to see this technology move closer to the patient," said TTO Executive Director Michael Haag. "The license and NeoIndicate’s award from the State of Ohio TVSF program helps to bring this technology one step closer to creating a meaningful impact."

On January 19, 2022 ESSA Pharma reported the first patient dosed in the Company-sponsored Phase I/II study to evaluate the safety, tolerability and preliminary efficacy of ESSA’s lead product candidate, EPI-7386, a first-in-class N-terminal domain androgen receptor inhibitor, in combination with Astellas Pharma and Pfizer’s ligand-binding domain androgen receptor inhibitor, enzalutamide, in patients with metastatic castration-resistant prostate cancer ("mCRPC") (Press release, ESSA, JAN 19, 2022, View Source [SID1234605589]).

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"The initiation of this combination trial with Astellas is a watershed moment for ESSA as we investigate the potential clinical benefit of inhibiting the androgen receptor through two independent pathways in the treatment of patients with mCRPC who have not yet received treatment with a second-generation antiandrogen drug," said Dr. David. R. Parkinson, Chief Executive Officer, ESSA Pharma Inc. "Combining our two therapies will simultaneously target both ends of the androgen receptor. In preclinical models, we have seen that combining EPI-7386 with current antiandrogens can lead to deeper and broader inhibition of androgen biology. This Phase 1/2 trial marks the first of a series of clinical studies to evaluate EPI-7386 in combination with current antiandrogen therapies in patients with mCRPC, with additional Phase 1/2 combination trials anticipated to begin in 2022."

The Phase 1/2 clinical trial (NCT05075577) begins with an initial phase 1 portion wherein the doses of each drug are adjusted followed by a phase 2 portion wherein the single agent enzalutamide is compared to the combination of enzalutamide and EPI-7386. The phase 1 study is expected to enroll up to 30 mCRPC patients who have not yet been treated with second-generation antiandrogen therapies. The goal of the phase 1 portion of the study is to evaluate the safety and tolerability of the drug combination and establish the recommended phase 2 doses for EPI-7386 and enzalutamide when dosed in combination. The phase 2 study is expected to enroll 120 mCRPC patients who have not yet been treated with second-generation antiandrogen therapies. The goal of the phase 2 part of the study is to evaluate the safety, tolerability and antitumor activity of EPI-7386 in combination with a fixed dose of enzalutamide compared with enzalutamide as a single agent.

About EPI-7386
EPI-7386 is an investigational, highly-selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor. EPI-7386 is currently being studied in a Phase 1 clinical trial (NCT04421222) in men with metastatic castration-resistant prostate cancer whose tumors have progressed on current standard-of-care therapies. The Phase I clinical trial of EPI-7386 began in calendar Q3 of 2020 following FDA allowance of ESSA’s Investigational New Drug application and Health Canada acceptance. EPI-7386 is also currently being studied in a Phase 1/2 clinical trial (NCT05075577) in mCRPC patients who have not yet been treated with second-generation antiandrogen therapies. The U.S. FDA has granted Fast Track designation to EPI-7386 for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA retains all rights to EPI-7386 worldwide.

On January 19, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported the presentation of the study design for its phase III trial, COMPOSE (NCT04919226), at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI), held from January 20 – 22, 2022 (Press release, , 19 19, 2022, View Source [SID1234605661]). COMPOSE will evaluate the company’s lead radiopharmaceutical candidate, ITM-11 (n.c.a. 177Lu-edotreotide), compared to best standard of care in patients with well‐differentiated high grade 2 and grade 3 somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (G2+G3 SSTR+ GEP-NETs). ITM-11 consists of the high-quality radioisotope, no-carrier-added lutetium-177 (n.c.a. 177Lu) chelated to the somatostatin analogue edotreotide. The aim of the study, in which patients are currently being randomized, is to evaluate the efficacy and safety of the Targeted Radionuclide Therapy in this high-need indication. COMPOSE is ITM’s second phase III trial with ITM-11 following and building upon COMPETE (NCT03049189), in patients with grade 1 and grade 2 GEP-NETs. Sponsor of the COMPOSE study is ITM’s subsidiary ITM Solucin GmbH.

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"We look forward to presenting the study design of COMPOSE to the medical and scientific community at ASCO (Free ASCO Whitepaper)-GI given the significant potential of ITM-11 as an innovative treatment modality"

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"We look forward to presenting the study design of COMPOSE to the medical and scientific community at ASCO (Free ASCO Whitepaper)-GI given the significant potential of ITM-11 as an innovative treatment modality," commented Philip E. Harris, MD PhD, Chief Medical Officer at ITM. "The favorable safety profile and efficacy signals observed to-date with our lead candidate give us reason to believe that ITM-11 can provide an important clinical benefit to patients diagnosed with this high-need indication and an advanced stage of this cancer."

COMPOSE (NCT04919226) is an international, prospective, randomized, controlled, open-label, multi-center phase III clinical trial to evaluate the efficacy, safety, and patient-reported outcomes of first or second-line treatment with ITM-11 compared to best standard of care in patients with well-differentiated high grade 2 and grade 3 (Ki-67 index 15-55), SSTR+ GEP-NETs. The study aims to randomize 202 patients 1:1 to ITM-11 or to best standard of care — either chemotherapy (CAPTEM or FOLFOX) or everolimus — according to the investigator’s choice. The primary endpoint of the study is progression-free survival (PFS), which will be assessed every 12 weeks from randomization onwards. Secondary outcome measures include overall survival (OS) up to two years after disease progression.

"With poor prognoses and limited treatment options for GEP-NETs, COMPOSE is an important step toward addressing a patient population with a high unmet medical need," commented Thorvardur Ragnar Halfdanarson, Principal Investigator of COMPOSE at the Mayo Clinic, Rochester, MN, USA. "Targeted Radionuclide Therapy continues to demonstrate promise for the treatment of hard-to-treat tumors. As such, I look forward to investigating its potential for patients with advanced GEP-NETs as we move ITM-11 through this Phase III trial."

Presentation information

Title: Pivotal phase III COMPOSE trial will compare 177Lu-edotreotide with best standard of care for well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumor

Abstract No: TPS514

Poster No: P5

Session: Trials in Progress Poster Session B: Pancreas, Small Bowel, and Hepatobiliary Tract

Presenter: Thorvardur Ragnar Halfdanarson, Mayo Clinic, Rochester, MN, USA

– End –

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, like 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 January 19, 2022 Marker Therapeutics, Inc. (NASDAQ:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that the United States Food and Drug Administration (FDA) Office of Orphan Products Development has granted Orphan Drug designation to MT-601, a multi-tumor-associated antigen (MultiTAA)-specific T cell product optimized for the treatment of patients with pancreatic cancer.

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"The FDA’s orphan drug designation underscores MT-601’s potential as a treatment for pancreatic cancer, a cancer typically diagnosed at an incurable advanced stage with a total overall 5-year survival rate of 10%," said Peter L. Hoang, President & CEO of Marker Therapeutics. "Our novel therapy has shown encouraging results in an ongoing Phase 1 trial sponsored by Marker’s partners at the Baylor College of Medicine. In results reported at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting, our therapy has demonstrated the potential to safely produce durable responses in combination with chemotherapy as a first-line treatment option for patients with advanced or metastatic pancreatic adenocarcinoma. The results also revealed that epitope spreading was consistent in responders to Multi-TAA-specific T cells. Following MT-401 for the treatment of post-transplant acute myeloid leukemia (AML), MT-601 is Marker’s second novel MultiTAA-specific T cell product to receive orphan drug designation and the first in a solid tumor indication, underscoring the potential of Marker’s multi-antigen targeting T cell therapy approach in both solid tumors and blood cancers."

Marker developed MT-601, a new product targeting six tumor-associated antigens (PRAME, NY-ESO-1, Survivin, MAGE-A4, SSX2, WT1) highly expressed in pancreatic cancer. The Company intends to initiate a Phase 1 multicenter study of MT-601 administered in combination with front-line chemotherapy to patients with locally advanced unresectable or metastatic pancreatic cancer. Marker designed the study to include an initial antigen escalation period followed by a dose escalation period and will enroll 20 – 25 patients for the study.

The Company plans to file an Investigational New Drug Application (IND) for MT-601 for the treatment of pancreatic cancer in 2022.

Orphan designation is granted by the FDA Office of Orphan Products Development to advance the evaluation and development of safe and effective therapies for the treatment of rare diseases or conditions affecting fewer than 200,000 people in the U.S. Under the Orphan Drug Act, the FDA may provide grant funding toward clinical trial costs, tax credits, FDA user-fee benefits, and seven years of market exclusivity in the United States following marketing approval by the FDA. The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. For more information about orphan designation, please visit the FDA website at www.fda.gov.

On January 19, 2022 Panavance Therapeutics Inc. ("Panavance") reported an abstract and poster at ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, January 20-22, 2022, in San Francisco, "A Phase 1/2 study to evaluate the safety, tolerability, and preliminary efficacy of GP-2250 in combination with gemcitabine for advanced or metastatic pancreatic adenocarcinoma," (authors: Dr. Anup Kasi and Dr. José Iglesias, Poster TPS620) (Press release, Panavance Therapeutics, JAN 19, 2022, View Source [SID1234605663]). The open-label trial for patients with advanced/metastatic pancreatic cancer who were previously treated with FOLFIRINOX is evaluating the safety and tolerability of escalating doses of GP-2250 together with gemcitabine.

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GP-2250 is a broadly active, tumor cell selective, small molecular weight, metabolic enzyme inhibitor with a first-in-class mechanism of action that limits aerobic glycolysis and Krebs cycle by inhibiting GAPDH, alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and the tumor promotor NFkB. In preclinical research, it suppresses cancer cells largely by disrupting their energy metabolism—bringing about cancer cell death.

The ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium abstract and poster describe a dose-escalation trial of GP-2250 (NCT03854110) in combination with gemcitabine in the 2nd-line treatment of metastatic pancreatic cancer patients who have progressed on or after FOLFIRINOX in the 1st-line treatment of the disease. The primary endpoints in the trial are the maximum tolerated dose ("MTD") and recommended Phase 3 dose.

"To date, we believe our GP-2250 has demonstrated strong effectiveness and safety in extensive preclinical studies, and its early clinical results have been encouraging for its initial indication for pancreatic cancer," said Greg Bosch, Chairman & Chief Executive Officer of Panavance. "We’re pleased with the progress of our ongoing Phase 1 trial which is currently at the 6th dose level with more than 20 patients enrolled thus far."

While Panavance’s initial area of focus is on pancreatic cancer, the company is conducting additional preclinical research in several other tumor types and expects to progress clinical development of GP-2250 for the treatment of other cancers.

Learn more about Panavance and GP-2250 at www.panavance.com.

References and links to websites have been provided for convenience, and the information contained on any such website is not a part of, or incorporated by reference into, this press release. Panavance is not responsible for the contents of third-party websites.