On June 8, 2021 ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, reported that it has been awarded an Innovation Partnership Programme (IPP) grant by Enterprise Ireland (EI) to fund collaborative research at Trinity College Dublin, Ireland, led by Dr. David Finlay to optimize the metabolism and engineering of NK cells for improved cancer therapies (Press release, ONK Therapeutics, JUN 8, 2021, View Source [SID1234583706]).

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!

Dr. Finlay, Associate Prof. in Immunometabolism in the Schools of Biochemistry and Immunology, and Pharmacy and Pharmaceutical Sciences, at Trinity College Dublin is a world-leading expert in NK cell metabolism. His group was the first to characterize cellular metabolic pathways in NK cells (reviewed in (1)) and to demonstrate the importance of NK cellular metabolism for the cytotoxic anti-tumor functions of these cells (2).

Active research is ongoing to optimize the efficacy of NK cell therapies against solid tumors by addressing the immunosuppressive tumor microenvironment (TME), where NK cell metabolism is impaired due to low glucose levels, oxygen deprivation (hypoxia), presence of inhibitory cytokines, and the higher concentration of tumor-derived metabolic end products, such as lactate.

To date, such improvement strategies to boost the efficacy of NK cells in the tumor microenvironment of solid cancers have centred on adding cytokines and other factors.

"We are taking a completely novel approach by addressing NK cell metabolism from the inside out, fundamentally engineering NK cells to better treat cancer by increasing their resistance to the adverse metabolic conditions generated by tumors," said Prof. Michael O’Dwyer, founder and CSO at ONK Therapeutics. "In working with Dr. Finlay, we are collaborating with the pioneering expert in the field of NK immunometabolism."

Under the terms of the collaboration, Trinity College Dublin retains any intellectual property (IP) arising out of the research collaboration, with ONK Therapeutics having an exclusive option to license the IP.

"In order to understand why cellular cancer immunotherapies are not effective in all cancer patients, scientists are actively trying to identify why certain patients respond and some do not and why some types of cancer can be successfully treated while others cannot. One emerging reason is that tumors can create metabolically unfavorable environments that might impact the effectiveness of immune cell therapies. My laboratory has the foremost expertise in NK cell metabolism placing us in a very strong position to address this challenge," said Dr. Finlay.

"Manipulating NK cell metabolism to enhance anti-cancer function is completely novel and is only possible based on our discoveries over the past five years," he said. "Our goal is to discover new targets within NK cells to be edited through CRISPR deletion or overexpression strategies. Detailed evaluation of the resistance of these cells to the adverse environments generated by tumors should support the development of enhanced NK cell therapies. It is an innovative approach to developing improved cellular therapies to treat cancer, in particular solid tumors."

Lawrence Lee, Manager, Innovation Partnership Programme Enterprise Ireland, said, "We are delighted to support this innovative research that has the potential to generate real and tangible benefits for cancer patients in Ireland and across the globe. The project is aligned with Enterprise Ireland’s strategic goal of supporting world-leading research in Ireland and fostering relationships between industry and academic partners. Research initiatives such as this have the capacity to further advance Ireland’s international research reputation and lay the foundations for the jobs of the future.

The Enterprise Ireland funding(3) covers 80% of the €373,295 project costs, with the industry partner, ONK Therapeutics providing €75,000 (20%) of the project costs. Trinity College Dublin will be recruiting two additional post-doctoral scientists into Dr. Finlay’s group over the two years of the project.

Chris Nowers, CEO of ONK Therapeutics, said, "We are highly ambitious in our goal to become a world-leading engineered NK cell therapy company that not only treats, but ultimately cures cancer. Our academic partnerships will deliver rich research insights and reinforce our own expertise as we aim to deliver new therapeutic options for patients in need."

1. O’Brien KL., Finlay, DK. (2019) Immunometabolism and Natural Killer cell responses. Nature Reviews Immunology, May;19(5):282-290. doi: 10.1038/s41577-019-0139-2

2. Assmann N, O’Brien KL, Donnelly RP, Dyck L, Zaiatz-Bittencourt V, Loftus RM, Heinrich P, Oefner PJ, Lynch L, Gardiner CM, Dettmer K, Finlay DK. (2017) Srebp-controlled glucose metabolism is essential for NK cell functional responses. Nature Immunology. Sep 18. doi: 10.1038/ni.3838

3. IP 2021 0976 – ‘Metabolic reprogramming and engineering of NK cells for improved cancer therapy’

On June 8, 2021 SHINE Medical Technologies LLC reported that it has entered a multi-year contract with the University of Missouri Research Reactor, or MURR, for irradiation of ytterbium-176, the starting material for the production of lutetium-177 (Lu-177), a therapeutic isotope showing great promise for improving patient outcomes for a range of cancers (Press release, Shine Medical Technologies, JUN 8, 2021, View Source;pk_kwd=shine-medical-announces-agreement-with-murr [SID1234583705]).

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!

"MURR’s experienced team and reliable reactor make its irradiation services invaluable to SHINE as we commercialize our Lu-177," said Katrina Pitas, vice president and general manager of SHINE Therapeutics. "MURR’s high neutron flux will help us produce all the non-carrier-added Lu-177 we need to serve our rapidly growing customer base, treating a wide variety of cancers."

MURR is located on the campus of the University of Missouri at Columbia.

"The MURR team looks forward to serving SHINE as it commercializes Lu-177," said Ken Brooks, associate director for business development at the MU Research Reactor. "For more than 50 years, MURR has served researchers and industry partners around the world."

Lu-177 is a low-energy beta-particle emitter that works by directly irradiating cancer cells after being delivered to the cancer site by a targeting molecule. Energy from Lu-177 only travels a short distance once it reaches cancer cells, enabling the isotope to destroy those cells with little damage to surrounding tissue. Lu-177-based therapy is approved by the U.S. Food and Drug Administration for the treatment of neuroendocrine cancers. It also shows promise for the treatment of metastatic prostate, breast, liver, brain and other cancers.

"The need for more effective cancer treatments continues to grow, particularly for those patients with metastatic or late-stage cancers," said Greg Piefer, SHINE’s founder and CEO. "We can help provide hope to those patients with a highly precise treatment that produces little damage in the tissue around the treatment site. SHINE expects to play a significant role in ensuring that patients around the world have access to Lu-177."

SHINE will host a booth in the SNMMI 2021 Virtual Exhibit Hall. The exhibit hall will be open June 11-15 as part of SNMMI’s Annual Meeting. The company will highlight its lutetium-177 product and progress on the commercialization of molybdenum-99.

On June 8, 2021 Clarity Pharmaceuticals, a clinical stage radiopharmaceutical company focused on the treatment of serious disease, reported that its clinical trial of 64/67Cu SARTATE for paediatric patients with neuroblastoma has been expanded to include five sites in the U.S (Press release, Clarity Pharmaceuticals, JUN 8, 2021, View Source [SID1234583704]).

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!

"We are very excited to expand into additional clinical sites which are now open for recruitment in the trial of Clarity’s lead product in neuroblastoma," commented Dr Alan Taylor, Clarity’s Executive Chairman. "Some of the initial data we have received to date from our first clinical site has been shared at one of the industry’s leading conferences, the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Mid-Winter Meeting 2021 and was very well received. We look forward to continuing the 64/67Cu SARTATE clinical trial in this important patient population in some of the leading cancer centres in the U.S."

The 67Cu SARTATE trial is a Peptide Receptor Radionuclide Therapy administered to paediatric patients with high-risk neuroblastoma. It is a multi-centre, dose-escalation, open label, non-randomised, Phase 1/2a theranostic clinical trial with the following confirmed clinical sites:1

Memorial Sloan Kettering Cancer Centre (MSK);
Cincinnati Children’s Hospital Medical Centre;
Medical University of South Carolina;
University of Texas Southwestern Medical Centre; and
University of Wisconsin.
Neuroblastoma most often occurs in children younger than 5 years of age and presents when the tumour grows and causes symptoms. It is the most common type of cancer to be diagnosed in the first year of life and accounts for around 15% of paediatric cancer mortality.2 High-risk neuroblastoma accounts for approximately 45% of all neuroblastoma cases. Patients with high-risk neuroblastoma have the lowest 5-year survival rates at 40%-50%.3

Dr Taylor said: "We are very pleased to have received strong support on the development of 64/67Cu SARTATE for neuroblastoma to date from numerous supporters, such as the five clinical sites, Clarity’s team, our collaborators, and the U.S. Food and Drug Administration in granting both diagnostic 64Cu SARTATE and therapeutic 67Cu SARTATE products Orphan Drug Designations and Rare Paediatric Disease Designations. We believe this highlights the importance of SARTATE development in this important patient population to improve the prognosis of children with high-risk neuroblastoma, where current treatment strategies are limited. We are looking forward to further progressing this trial at five clinical sites and getting closer to our ultimate goal of better treating children and adults with cancer."

References
ClinicalTrials.gov Identifier: NCT04023331
Nadja C. Colon and Dai H. Chung 2011, "Neuroblastoma", Advances in Pediatrics, <View Source>
Valeria Smith and Jennifer Foster 2018, "High Risk Neuroblastoma Treatment Review", Children, <View Source>

On June 8, 2021 Nascent Biotech, Inc. (OTCQB:NBIO) ("Nascent Biotech", "Nascent", or the "Company"), a clinical-stage biotechnology Company pioneering the development of monoclonal antibodies targeting treatment of various cancers and viral infections, reported the beginning of enrollment of the second cohort in dosing patients for its Phase I trial for Brain Cancer (Press release, Nascent Biotech, JUN 8, 2021, View Source [SID1234583703]). This milestone allows the trial to triple the dosage levels over the first cohort to achieve the highest level without toxicity.

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!

Patient enrollment continues for Phase I. Anyone interested may review trial requirements at www.clinicaltrials.gov, then search Pritumumab.

"Having completed the first cohort in a very short time, we are now in our second dose escalation with the second cohort being enrolled," noted Nascent CEO, Sean Carrick.

PTB is a natural human antibody that works by binding to Cell surface Vimentin (also referred to as ectodomain vimentin, or EDV), a protein expressed on the surface of epithelial cancers. PTB is used as a targeted immunotherapy unlike chemotherapy targets only cancer cells without damaging healthy cells."

On June 8, 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 cancer and castrate-resistant prostate cancer, reported that the first patient has been dosed in its Phase 2 clinical trial of onvansertib in combination with nanoliposomal irinotecan and 5-FU as a second-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC) (Press release, Cardiff Oncology, JUN 8, 2021, View Source [SID1234583702]).

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 Phase 2 open-label, multicenter trial, which is an integral part of Cardiff Oncology’s focus on KRAS-mutated solid tumor cancers, is designed to assess the safety and preliminary efficacy of onvansertib in combination with standard-of-care as a second-line treatment in patients with metastatic PDAC who have failed first-line gemcitabine-based therapy. The trial is expected to enroll approximately 40 patients across six sites in the U.S., including the three Mayo Clinic Cancer Centers (Arizona, Minnesota and Florida), Kansas University Medical Center, The University of Nebraska Medical Center and Inova Schar Cancer Institute.

"We believe that adding onvansertib to standard-of-care therapy may improve the current dim prognosis for PDAC patients where currently second-line treatment confers only a 7.7% response rate and 3.1-month median progression-free survival," said Daniel H. Ahn, D.O., principal investigator for the trial and medical oncologist, Mayo Clinic Cancer Center, Arizona. "There is increasing evidence in the ongoing Phase 2 trial in KRAS-mutated mCRC that the synergistic effect of onvansertib in combination with irinotecan and 5-FU is resulting in meaningful clinical benefit and improving outcomes for patients with KRAS-mutated cancers and we are optimistic that we will see similar results in this PDAC trial."

Dr. Mark Erlander, chief executive officer of Cardiff Oncology added, "Onvansertib’s inhibitory effect on the proliferation and survival of KRAS-mutated tumor cells has, notably, shown synergistic clinical benefit in combination with irinotecan and 5-FU in our KRAS-mutated metastatic colorectal cancer trial (mCRC). As metastatic PDAC tumors bear KRAS mutations about 95% of the time, we see an opportunity for onvansertib to improve response rates and increase progression-free survival in this indication with such marked unmet need. The dosing of the first patient in our Phase 2 PDAC trial represents an important step in pursuit of this opportunity, and we look forward to its continued progress."
About the Phase 2 Trial of Onvansertib in Metastatic PDAC
This trial is an open-label, multi-center study designed to assess the safety and efficacy of onvansertib in combination with nanoliposomal irinotecan (Onyvide), leucovorin, and 5-FU as

a second-line treatment in patients with metastatic PDAC. The trial is expected to enroll approximately 40 patients with histologically confirmed measurable and metastatic PDAC who have failed treatment with one prior line of gemcitabine-based chemotherapy. Patients will receive nanoliposomal irinotecan, leucovorin, and 5-FU on Day 1 of 14-day cycles in combination with onvansertib 12 mg/m2 on Days 1-10, or 15 mg/m2, on Days 1-5 of each 14-day cycle. The study will be conducted at six clinical trial sites across the U.S: Mayo Clinic (Arizona, Minnesota, Florida), Kansas University Medical Center, The University of Nebraska Medical Center and Inova Schar Cancer Institute. The primary endpoint will be objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Key secondary and exploratory endpoints include duration of response, median overall survival, ORR in patients receiving more than two treatment cycles, disease control rate (defined as complete response, partial response or stable disease by RECIST v1.1 over the entire treatment period), and assessment of KRAS allelic burden in liquid biopsies as measured by circulating tumor DNA (ctDNA). Please refer to clinicaltrials.gov NCT04752696 for additional clinical trial information.