On April 13, 2021 RubrYc Therapeutics, Inc., a pre-clinical biotherapeutics company developing epitope selective therapies, reported that it has entered into a research collaboration and license option agreement with Zai Labs, Inc. for the use of RubrYc’s Meso-scale Engineered Molecules (MEMs) platform, to identify monoclonal antibodies with enhanced biological function for an undisclosed oncology target (Press release, RubrYc Therapeutics, APR 13, 2021, View Source [SID1234577992]).

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Under the terms of the agreement RubrYc and Zai Labs will collaborate to identify product candidates using RubrYc’s Discovery Engine, which leverages machine learning and structural data to identify antibodies that bind to subdominant epitopes and exhibit differentiated activity. Upon exercise of the license option Zai Labs would have exclusive global rights to develop and commercialize product(s) of the Research Collaboration.

RubrYc Therapeutics, Inc. will receive an upfront payment and is eligible to receive future research, development and commercialization milestones on a per candidate basis, along with royalties on world-wide net sales of each product. Financial terms of the agreement were not disclosed.

Dr. Isaac Bright, CEO, said, "We are excited that Zai Labs has selected the RubrYc Discovery Engine as part of its efforts to identify biotherapeutics against challenging oncology targets. We look forward to collaborating with Zai Labs to accelerate their research by identifying epitope-specific antibodies with differentiated modes of action. Zai Labs’ oncology expertise complements our interest in bringing novel therapeutics with breakthrough potential to patients in need."

On April 13, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) reported that the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Trodelvy (sacituzumab govitecan-hziy) for use in adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor (Press release, Gilead Sciences, APR 13, 2021, View Source [SID1234577991]). The accelerated approval was based on data from the international Phase 2, single-arm TROPHY study. Of the 112 patients who were evaluable for efficacy, 27.7% of those treated with Trodelvy responded to treatment, with 5.4% experiencing a complete response and 22.3% experiencing a partial response. The median duration of response was 7.2 months (95% CI: 4.7-8.6). The Trodelvy U.S. Prescribing Information has a BOXED WARNING for severe or life-threatening neutropenia and severe diarrhea; see below for Important Safety Information.

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The FDA’s accelerated approval mechanism enables drugs that treat serious diseases with unmet medical need to be approved based on a surrogate or intermediate clinical endpoint. Continued approval is contingent upon verification and description of clinical benefit in a confirmatory trial.

"Only a fraction of patients derives long-term benefit from previously approved cytotoxic therapy or immunotherapy, leaving a great unmet need for treatment options for patients with advanced urothelial cancer who have progressed on first- and second-line therapies," said Scott T. Tagawa, MD, MS, FACP, Professor of Medicine and Urology at Weill Cornell Medicine, an oncologist at New York-Presbyterian/Weill Cornell Medical Center and principal investigator of the TROPHY study.i "The response rate and tolerability seen with sacituzumab govitecan-hziy may provide physicians an effective new treatment option for patients whose cancer continues to progress even after multiple therapies."

UC is the most common type of bladder cancer and occurs when the urothelial cells that line the inside of the bladder and other parts of the urinary tract grow unusually or uncontrollably. An estimated 83,000 Americans will be diagnosed with bladder cancer in 2021, and almost 90% of those diagnoses will be UC. The relative five-year survival rate for patients with metastatic UC is 5.5%.

"Cases of urothelial cancer continue to rise in the U.S., yet prognosis remains the same for the vast majority of patients," said Andrea Maddox-Smith, CEO of the Bladder Cancer Advocacy Network (BCAN). "Bladder cancer patients need as many treatment options as possible, and we are pleased that Trodelvy can be a potentially viable treatment for them."

Trodelvy’s safety profile in the TROPHY study is consistent with previous observations in metastatic UC and other tumor types. Among all evaluable treated metastatic UC patients (n=113), the most common (≥25%) adverse reactions were diarrhea (72%), anemia (71%), fatigue (68%), neutropenia (67%), nausea (66%), alopecia (49%), decreased appetite (41%), constipation (34%), vomiting (34%) and abdominal pain (31%). Adverse reactions leading to treatment discontinuation occurred in 10% of those receiving Trodelvy, with 4% discontinuing treatment due to neutropenia.

"Today’s accelerated approval is thanks to the patients and healthcare professionals involved in the TROPHY study, and we appreciate their partnership," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "This achievement, coupled with last week’s full FDA approval in unresectable locally advanced or metastatic triple-negative breast cancer, underscores our commitment toward rapidly delivering Trodelvy to patients facing some of the most difficult-to-treat cancers."

A global, randomized Phase 3 confirmatory clinical trial TROPiCS-04 (NCT04527991) is underway and is also intended to support global registrations. More information on TROPiCS-04 is available at View Source

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein frequently expressed in multiple types of epithelial tumors, including metastatic triple-negative breast cancer (TNBC) and metastatic UC, where high expression is associated with poor survival and relapse.

In addition to the accelerated approval of Trodelvy for the treatment of locally advanced or metastatic UC, Trodelvy is approved in the U.S. to treat adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.

Beyond the regulatory approvals of Trodelvy in the U.S., regulatory reviews for Trodelvy in metastatic TNBC are currently underway in the EU, U.K., Canada, Switzerland and Australia, as well as in Singapore through our partner Everest Medicines. Trodelvy is also being developed as an investigational treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER 2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.

About the TROPHY U-01 Study

The Phase 2 TROPHY-U01 (also known as IMMU-132-06) trial is an ongoing, international, multi-center, open-label, multi-cohort, single-arm study evaluating Trodelvy monotherapy or combination therapy in patients with metastatic UC after progression on a platinum-based regimen and anti-PD-1/PD-L1-based immunotherapy. In Cohorts 1 and 2, patients received Trodelvy 10 mg/kg administered intravenously on Days 1 and 8 of a 21-day cycle to be continued until disease progression or loss of clinical benefit. Trodelvy is approved under accelerated approval based on the objective response rate (ORR) and duration of response (DoR) established in Cohort 1.

Cohorts 2, 3, 4 and 5 of the study are ongoing. Cohort 2 is assessing the safety and efficacy of Trodelvy monotherapy in platinum-ineligible patients after progression on anti-PD-1/PD-L1-based immunotherapy. Cohort 3 is assessing the safety and efficacy of Trodelvy on Days 1 and 8 of a 21-day cycle followed by pembrolizumab at the standard approved dose (200 mg) only on Day 1 of a 21-day cycle in patients with metastatic UC who have progressed after prior platinum therapy. Cohorts 4 and 5 are assessing the safety and efficacy of Trodelvy combination therapy in patients with treatment naive metastatic UC, with those in Cohort 4 receiving cisplatin and those in Cohort 5 receiving cisplatin and avelumab, respectively, in addition to Trodelvy.

The primary endpoint is ORR based on RECIST 1.1 criteria evaluated by independent central review in all five cohorts. In Cohorts 1 and 2, secondary endpoints are DoR and progression-free survival (PFS) based on central review and overall survival (OS). Secondary endpoints in Cohorts 3, 4 and 5 include DoR, clinical benefit rate (CBR) and PFS based on central review by RECIST 1.1 criteria; DoR, CBR and PFS based on investigator review by RECIST 1.1 and iRECIST criteria, OS and safety and tolerability of Trodelvy in combination with pembrolizumab, cisplatin, or cisplatin and avelumab, depending on the Cohort. More information about TROPHY is available at View Source

Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to TRODELVY.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 61% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 7%. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever.

Diarrhea: Diarrhea occurred in 65% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation following diarrhea. Neutropenic colitis occurred in 0.5% of patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with TRODELVY. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.3%. The incidence of anaphylactic reactions was 0.3%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions

Nausea and Vomiting: Nausea occurred in 66% of all patients treated with TRODELVY and Grade 3 nausea occurred in 4% of patients. Vomiting occurred in 39% of patients and Grade 3-4 vomiting occurred in 3% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia in genotyped patients was 67% in patients homozygous for the UGT1A1*28, 46% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia in genotyped patients was 25% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 11% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

ADVERSE REACTIONS

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite, and abdominal pain. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced hemoglobin, lymphocytes, leukocytes, and neutrophils.

In the TROPHY study (IMMU-132-06), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, neutropenia, nausea, alopecia, anemia, decreased appetite, constipation, vomiting, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY.

UGT1A1 Inducers: Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY.

On April 13, 2021 Molecular Targeting Technologies, Inc. (MTTI) reported the issuance of United States Patent # 10,953,113. The patent claims a quick (5 min), easy and quantitative conversion of commercially available 18F-deoxyglucose (18F-FDG) to 18F-Fluroglucaric acid (18F-FGA) (Press release, Molecular Targeting Technologies, APR 13, 2021, View Source [SID1234577990]).

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Professor Fabian Kiessling, MD, Director of the Institute for Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany commented, "In addition to monitoring tumor response to therapy, a tracer that sees necrosis should track organ fibrosis in chronic kidney disease and liver fibrosis. These diseases are common, but their progression and responses to therapy are still hard to track reliably. 18F-FGA could be extremely valuable to fill this unmet medical need."

Professor Vibhudutta Awasthi, PhD, Associate Dean of Research, inventor and co-inventor Dr. Hailey Houson at the University of Oklahoma said, "An 18F-FGA imaging agent for necrosis can revolutionize a diagnostic workup of many human diseases where tissue necrosis occurs as part of the pathology. This tracer enables use of high resolution, high sensitivity PET, to detect myocardial infarction and brain stroke. We are delighted to hear about MTTI’s effort to commercialize this technology."

"The search for agents that could image necroses, without accumulating in living tissue, has been going on for decades. This innovative 18F PET tracer is specific for dead cells. It is also ideal for monitoring rapid tumor response to radiation and drug treatment. We’re excited for this discovery and look forward to advancing this molecule to clinic," said Chris Pak, President & CEO of MTTI.

On April 13, 2021 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for medical imaging and therapeutic applications, reported a corporate update highlighting progress across its key programs during the past twelve months and upcoming milestones (Press release, NorthStar Medical Radiostopes, APR 13, 2021, View Source [SID1234577989]).

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"NorthStar has made significant advancements across our portfolio over the past year and we are excited about the Company’s future," said Stephen Merrick, President and Chief Executive Officer of NorthStar Medical Radioisotopes. "In advancing our plans to ensure reliable, non-uranium based radioisotope supply for the United States, RadioGenix System (technetium Tc 99m generator) sales continue to increase. Our facility expansions, designed to ensure additional production capacity and supply of Mo-99, are nearing completion. Additionally, NorthStar has broadened its technology platform to address critical unmet needs in radioisotope supply by advancing commercial-scale development of promising therapeutic radioisotopes, and our novel cardiovascular SPECT imaging agent, FibroScint, is advancing towards eIND-enabling studies. We are collaborating with IBA to increase global availability of Tc-99 and with Monopar Therapeutics to develop a targeted radiotherapeutic agent for severe COVID-19 and other acute respiratory diseases. NorthStar anticipates sustained progress and growth as we expand our horizons globally and execute strongly in our mission to provide reliable radioisotope supply to support patients’ healthcare needs."

Corporate development and industry leadership
NorthStar is firmly positioned for long term growth and increasing global industry leadership.

In March 2021, NorthStar implemented organizational changes to drive focused growth for its therapeutic and specialized SPECT radioisotopes business. The new structure enables NorthStar to advance its radioisotope development and commercialization planning efforts in parallel with ongoing expansion programs for increased U.S. Mo-99 capacity and production. In conjunction with other organizational changes, NorthStar appointed Dave Wilson, RPh, BCNP, as Vice President, Advanced Radiopharmaceutical and Therapeutic Technologies to lead these initiatives to commercialization.
In October 2020, NorthStar promoted Chief Financial Officer Paul Estrem to Executive Vice President and he was appointed to the NorthStar Board of Managers. Mr. Estrem has been instrumental in building momentum to create and expand NorthStar’s product portfolio. The expanded role positions him to guide NorthStar’s corporate strategy and drive its planned corporate and business development initiatives.
NorthStar is a widely recognized leader in radioisotope technology development and commercialization and the nuclear medicine industry. In July 2020, NorthStar led an update on its ongoing commercial Mo-99 production, expansion plans and the RadioGenix System at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) event, "Industry Outlook on Current and Future Mo-99 Supply." In September 2020, then-Deputy Secretary of Energy Mark W. Menezes visited NorthStar to learn about its U.S.-based Mo-99 production, underscoring the Department of Energy’s commitment to reviving and expanding the U.S. nuclear sector and to reduce dependence on foreign imports while bringing new opportunities to the heartland.
RadioGenix System commercial progress
NorthStar’s innovative, high tech radioisotope separation platform, the RadioGenix System, uses U.S.-produced, non-uranium based Mo-99 to produce Tc-99m, the most widely used medical radioisotope that informs patient management decisions in 40,000 U.S. imaging studies daily.

RadioGenix System sales continue to steadily increase, with hundreds of thousands of doses provided for patients’ diagnostic imaging studies to date. Since becoming commercially available, RadioGenix Systems have provided reliable Tc-99m supply for customers with U.S.-produced Mo-99, despite intermittent shortages from suppliers using legacy, uranium-based production methods.
Ongoing product development programs continue to maximize operational utility and efficiency in producing Tc-99m. Since initial approval in 2018, NorthStar has received five subsequent Food and Drug Administration (FDA) approvals, the latest in January 2021 for concentrated Mo-98 and RadioGenix System updates.
Commercial U.S. Mo-99 manufacturing and production expansion
NorthStar is the only commercialized U.S. producer of Mo-99. It is aggressively expanding and establishing dual production and processing hubs for additional Mo-99 capacity to better meet customer demand and to ensure sustainable U.S. supply. Two facility expansion projects nearing completion in Beloit, Wisconsin, will augment current Mo-99 production and processing in Columbia, Missouri, conducted in partnership with the University of Missouri Research Reactor (MURR).

NorthStar’s Isotope Processing facility in Beloit will complement current Columbia processing capacity for Mo-99 source vessels. The facility will enable NorthStar to more than double its production of Mo-99, used with RadioGenix Systems to produce Tc-99m. Equipment installation is nearing completion, testing is underway with full qualification to be completed by the end of 2021. NorthStar expects FDA approval for the Beloit Isotope Processing facility in 2022.
NorthStar’s Accelerator Production facility expansion in Beloit will ensure additional Mo-99 capacity, enable flexible production scheduling and minimize customer supply risks. Like other NorthStar processes, accelerator production of Mo-99 using the "neutron knock-out" method is non-uranium based and highly efficient. The first pair of IBA electron beam accelerators will arrive for installation at NorthStar’s facility in April 2021. The Company anticipates accelerator production to begin in 2023, pending appropriate licensure and FDA approval.
In January 2021, the FDA approved NorthStar’s process for producing Mo-99 from concentrated Mo-98 and related software updates for the RadioGenix System. This approval is the first and only commercial-scale production of Mo-99 using concentrated Mo-98 technology. It increases NorthStar’s Mo-99 production capacity up to four times above its current technology, to provide higher activity source vessels to better meet customer demand.
FDA approval of concentrated Mo-98 allows NorthStar to serve as much as 40% of the U.S. demand for Mo-99 by the end of 2021. The Company expects that within three to five years, it will have the capability to regularly supply an estimated 65% of U.S. Mo-99 demand, and up to 100% of U.S. demand in an emergency.
Commercial-scale therapeutic radioisotope production − Ac-225 and Cu-67
NorthStar is poised to be the first commercial-scale supplier of the important therapeutic radioisotopes Ac-225 and Cu-67, both used to directly target and deliver therapeutic doses of radiation to destroy cancer cells in patients with serious disease. Current production technology limitations and resultant limited supply have severely constrained development of these promising therapies.

NorthStar is applying its commercial-scale radioisotope production expertise to provide reliable Ac-225 and Cu-67 supply to advance clinical research and for commercial radiopharmaceutical products. The Company is leveraging the same technology expertise demonstrated by the successful launch of the RadioGenix System and non-uranium based Mo-99 supply.
NorthStar has relationships in place with several large pharmaceutical companies to provide clinical trial supply and commercial-scale quantities of Ac-225 and Cu-67. The Company expects to secure long-term supply agreements during 2021.
Specialized SPECT portfolio
NorthStar is actively developing and growing its strategic portfolio of specialized single photon emission computed tomography (SPECT) radiopharmaceuticals to meet increasing clinical needs for SPECT imaging, driven by scientific advancements in cardiology and oncology.

NorthStar has an exclusive, global licensing agreement with Capella Imaging, Inc. for FibroScint, a novel fibrin-specific diagnostic imaging agent labeled with Tc-99m for SPECT imaging. Pending successful development, FibroScint will have an initial application in the imaging of thrombus (blood clots) associated with left ventricular assist devices (LVADs), and other potential imaging applications in deep vein thrombosis and pulmonary embolism. NorthStar intends to use RadioGenix System-produced Tc-99m in planned clinical studies of FibroScint. Advanced preclinical development is underway, with an exploratory Investigational New Drug (IND) filing for a Phase 1 study planned for early 2022.
NorthStar is evaluating additional potential opportunities in specialized SPECT radiopharmaceuticals to address unmet healthcare needs and synergies with its product portfolio.
Partnerships and collaborations
NorthStar selectively partners with leading organizations in strategic collaborations designed to augment its portfolio, maximize synergies and drive growth in areas of unmet medical need.

In June 2020, NorthStar and Monopar Therapeutics Inc. (Nasdaq: MNPR) announced a collaboration to help combat severe COVID-19 and other severe respiratory diseases. The collaboration will couple Monopar’s targeted monoclonal antibody MNPR-101 to a therapeutic radioisotope supplied by NorthStar to create a highly selective agent with potential to spare healthy cells while quickly reducing cytokine storms and their harmful systemic effects. In December 2020, Monopar and NorthStar announced that a clinical candidate was selected, enabling preclinical studies to begin and advancing one step closer to reaching human clinical trials.
In March 2021, NorthStar and IBA (Ion Beam Applications S.A., EURONEXT) announced a collaboration to increase global availability of Tc-99m, with potential to result in non-uranium Mo-99 being the leading worldwide source of Tc-99m. Worldwide, diagnostic imaging studies using Tc-99m inform healthcare decisions for approximately 30 million patients annually. The collaboration enables companies outside the United States to access Tc-99m Generation Systems (TCM Generation Systems) that utilize NorthStar’s proprietary non-uranium based Mo-99 produced using IBA’s accelerators and beamlines. Early discussions with interested companies are underway.
About the RadioGenix System (Technetium Tc 99m Generator)
The RadioGenix System is an innovative, high tech separation platform that is approved for processing non-uranium based molybdenum-99 (Mo-99) for the production of the important medical radioisotope, technetium-99m (Tc-99m). Prior to availability of RadioGenix technology, the U.S. supply chain for Mo-99 has been subject to frequent and sometimes severe interruptions which negatively impact patient healthcare. Approved by the U.S. Food and Drug Administration (FDA) in 2018, the RadioGenix System is the first and only on-site, automated isotope separation system of its kind for use with non-uranium based Mo-99, designed to help alleviate shortage situations and expand domestic supply.

Indication and Important Risk Information about the RadioGenix System and Sodium Pertechnetate Tc 99m Injection USP

The RadioGenix System is a technetium Tc-99m generator used to produce Sodium Pertechnetate Tc 99m Injection, USP. Sodium Pertechnetate Tc 99m Injection is a radioactive diagnostic agent and can be used in the preparation of FDA-approved diagnostic radiopharmaceuticals.

Sodium Pertechnetate Tc 99m Injection is also indicated in

Adults for Salivary Gland Imaging and Nasolacrimal Drainage System Imaging (dacryoscintigraphy).
Adults and pediatric patients for Thyroid Imaging and Vesicoureteral Imaging (direct isotopic cystography) for detection of vesicoureteral reflux.
IMPORTANT RISK INFORMATION

Allergic reactions (skin rash, hives, or itching) including anaphylaxis have been reported following the administration of Sodium Pertechnetate Tc 99m Injection. Monitor all patients for hypersensitivity reactions.
Radiation risks associated with the use of Sodium Pertechnetate Tc 99m Injection are greater in children than in adults and, in general, the younger the child, the greater the risk owing to greater absorbed radiation doses and longer life expectancy. These greater risks should be taken firmly into account in all benefit-risk assessments involving children. Long-term cumulative radiation exposure may be associated with an increased risk of cancer.
Unintended Re-186 Exposure: Discard the first eluate from every new Potassium Molybdate Mo-99 Source Vessel to minimize the risk of unintended radiation exposure from Rhenium Re-186.
Temporarily discontinue breastfeeding. A lactating woman should pump and discard breastmilk for 12 to 24 hours after Sodium Pertechnetate Tc 99m Injection administration.
Sodium Pertechnetate Tc 99m Injection should be given to pregnant women only if the expected benefits to be gained clearly outweigh the potential hazards.
Only use potassium molybdate Mo-99, processing reagents, saline and other supplies, including kit/packs, provided by NorthStar Medical Radioisotopes. Do not administer Sodium Pertechnetate Tc 99m Injection after the 0.15 microCi of Mo-99/mCi of Tc-99m limit has been reached or when the 24 hour expiration time from elution is reached, whichever occurs earlier.

On April 13, 2021 LintonPharm Co., Ltd., a China-based clinical stage biopharmaceutical company focused on the development of T cell engaging bispecific antibodies for cancer immunotherapy, reported that China’s health authority, National Medical Products Administration (NMPA) authorized the company to proceed with a Phase 1/2 clinical trial (clinicaltrials.gov: NCT04799847) evaluating the safety and efficacy of catumaxomab in patients with Non-Muscle-Invasive Bladder Cancer (NMIBC) whose tumors have recurred due to Bacillus Calmette-Guerin (BCG) vaccine failure (Press release, Lintonpharm, APR 13, 2021, View Source [SID1234577988]). This is LintonPharm’s second clinical program evaluating catumaxomab. In July 2020, the company announced authorization of a Phase 3 trial in advanced gastric cancer which screened its first patient in October 2020.

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Recently, Lindis Biotech, partner of LintonPharm, initiated a dose-finding Phase 1 trial with catumaxomab in NMIBC patients in Germany (clinicaltrials.gov: NCT04819399) and reported an excellent safety profile, which supports the conduct of the Phase 1/2 trial in China.

"Regulatory clearance to move forward with our clinical program evaluating catumaxomab in bladder cancer is another significant milestone for LintonPharm and supports our goal of exploring the potential for this targeted therapy in a broad range of cancers," said Robert Li, Ph.D., DABT, Co-founder and CEO of LintonPharm. "Patients with NMIBC BCG failure have high rates of tumor recurrence and often face a lifetime of surgical intervention which may impact bladder function. New treatment options are needed and we are hopeful that this study puts us one step closer toward helping these patients."

Bladder cancer is the 10th most common cancer worldwide. In 2020, bladder cancer was diagnosed in approximately 573,278 patients globally and approximately 1.8 million people were living with this form of cancer over a five-year period [1]. NMIBC is a cancer found in the tissue that lines the inner surface of the bladder and accounts for approximately 75 percent of all bladder cancer [2]. Transurethral resection of bladder tumor (TURBT) is the current standard of treatment for NMIBC. Relapse is common after TURBT (up to 70 percent at five years) and as a result, patients often undergo multiple surgical procedures over a longer period [2]. Intravesical BCG is commonly used as an adjuvant treatment after TURBT. However, a large number of patients experience tumor recurrence, which is referred to as BCG failure [3]. Radical cystectomy (RC) is usually recommended after BCG failure, but many physicians and patients refrain from RC in favor of preserving bladder function.

About Catumaxomab

Catumaxomab was approved by the European Medicines Agency in 2009 for the treatment of malignant ascites. This bispecific antibody binds to a transmembrane glycoprotein on the tumor cell–the epithelial cell adhesion molecule (EpCAM)–and CD3 on the T cell, and also recruits immune accessory cells through FcγR binding. Catumaxomab destroys tumor cells by engaging T cell and accessory cell mediated cytotoxicity and has the potential to induce long-term vaccinal effects which has been verified in animal models.

Recently, catumaxomab was authorized by regulatory authorities in China, Taiwan (China) and South Korea to conduct a global Phase 3 clinical trial for treating patients with advanced gastric cancer.