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]).

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"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]).

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"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.

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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]).

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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.

On June 8, 2021 Byondis B.V. reported positive topline results from the Phase III TULIP study, a multi-center, open-label, randomized clinical trial (Press release, Byondis, JUN 8, 2021, View Source [SID1234583701]). The trial compared the efficacy and safety of the company’s antibody-drug conjugate (ADC) [vic-]trastuzumab duocarmazine (SYD985) to physician’s choice treatment in patients with pretreated HER2-positive unresectable locally advanced or metastatic breast cancer (MBC).

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The Phase III TULIP study "SYD985 vs. Physician’s Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer" met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement over physician’s choice. PFS is defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurred earlier. The study also demonstrated preliminary supportive overall survival (OS) results.

"There is considerable unmet medical need in patients with HER2-positive metastatic breast cancer and [vic-]trastuzumab duocarmazine represents a promising potential clinical advance," said Byondis Chief Medical Officer Jan Schellens, M.D., Ph.D. "We are excited by the topline results of TULIP and indebted to all patients who participated in the clinical studies."

Byondis CEO Marco Timmers, Ph.D., referred to the study’s culmination as a triumph over adversity. "A large trial involving breast cancer patients with advanced disease is difficult in the best of times, but it is especially challenging during a global pandemic. The completion of TULIP is a testament to the dedication of all involved, especially the patients, their families and participating clinical sites."

Detailed results from TULIP will be published at scientific conferences in due course. Byondis will complete the biological license application (BLA) and intends to submit it before the end of 2021.

With this positive study outcome, Byondis is planning to explore partnerships with pharma and biopharma companies in order to commercialize SYD985 and make it available to patients in need of new treatment options.

SYD985 was granted fast track designation by the U.S. Food & Drug Administration in January 2018 based on promising data from heavily pre-treated last-line HER2-positive MBC patients participating in a two-part Phase I clinical trial (SYD985.001).[1]

About TULIP (SYD985.002)

Begun in November 2017, TULIP enrolled a total of 436 female patients aged 18 and over, at 83 sites across the United States, Canada, Europe and Singapore. To qualify, patients had either: (1) progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease; or (2) progression during or after ado-trastuzumab emtansine treatment. Patients were randomly assigned (2:1) to receive SYD985 or physician’s choice treatment until disease progression or unacceptable toxicity.

In addition to blinded, independent, centrally reviewed PFS, the trial’s secondary objectives were to compare the two treatment groups with respect to: (1) overall survival (OS); (2) objective response rate (ORR) on the basis of the blinded independent central review; (3) investigator-assessed PFS; (4) patient-reported outcomes (PRO) for health-related quality of life; and (5) safety and tolerability.

[Vic-]Trastuzumab Duocarmazine (SYD985), a Next Generation Antibody-Drug Conjugate

[Vic-]trastuzumab duocarmazine (SYD985) incorporates Byondis’ distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine. Although in general, marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still need for improvement.

The ADC [vic-]trastuzumab duocarmazine is comprised of the monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of [vic-]trastuzumab duocarmazine binds to HER2 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD985 is considered a form of targeted chemotherapy.

[Vic-]trastuzumab duocarmazine is currently being investigated in four other studies. Byondis initiated a Phase II clinical trial in HER2-expressing recurrent, advanced or metastatic endometrial cancer and a Phase I study exploring the synergistic effects of [vic-]trastuzumab duocarmazine and niraparib in patients with HER2-expressing locally advanced or metastatic solid tumors. [Vic-]trastuzumab duocarmazine is also part of two Quantum Leap Health Collaborative trials: a new arm of the I-SPY 2 TRIAL investigating the neoadjuvant use of [vic-]trastuzumab duocarmazine in HER2-low early-stage breast cancer; and a Phase I combination trial with paclitaxel in solid tumors.

ByonZine, Byondis’ Distinctive, Proprietary Linker-Drug Technology

While earlier generation ADCs improved targeting and cell killing, they were unstable in the bloodstream, leading to premature release of the cytotoxic payload, impacting healthy tissue and narrowing the therapeutic window. Byondis’ next generation ADCs are highly stable in circulation and carry an intricate, inactivated and potent cytotoxic drug that rapidly self-destructs in case it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window.

Byondis’ differentiated linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.

The distinctive design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower HER2 expression may improve the efficacy potential, the so-called bystander effect.

HER2-Positive MBC: A Cancer With a Poor Prognosis

Breast cancer was the world’s most common cancer in 2020,[2] with an estimated 2.3 million new cases.[3] Its incidence is rising, particularly in developing countries, where the majority of cases are diagnosed in late stages.[4] Breast cancer is the leading cause of cancer death for women in over 100 countries.[5]

In metastatic or Stage 4 breast cancer, the cancer spreads to other parts of the body, such as the lungs, liver, bones or brain. Approximately 0.5 million people worldwide die from MBC every year.[6]

In HER2-positive breast cancer, an overexpression of the human epidermal growth factor receptor 2 (HER2) protein causes out-of-control reproduction of breast cells. Research has shown that women with HER2-positive breast cancer have a more aggressive disease, greater likelihood of recurrence and poorer prognosis, compared to women with HER2-negative breast cancer. About 20 percent of all breast cancers are HER2-positive, with younger women being the most affected. Treatment of HER2-positive breast cancer can consist of the following: surgery, radiation, chemotherapy and targeted treatments.[7]