On March 29, 2022 Alphamab Oncology (stock code: 9966.HK) reported financial results for the full year ended December 31, 2021 and highlighted recent progress and upcoming milestones (Press release, Alphamab, MAR 29, 2022, View Source [SID1234611143]).

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Highlights

First product launch: In November 2021, KN035 (Envafolimab) has received marketing authorization from the Chinese National Medical Products Administration (NMPA), becoming the world’s first and currently only subcutaneously injected PD-L1 antibody approved for marketing.
First year of commercialization: We recorded total revenue of RMB146.0 million yuan for the year ended December 31, 2021, of which RMB11.62 million yuan of revenue from the shipment of Envafolimab, RMB134 million yuan of revenue from KN026.
Rapid advancement of pivotal clinical trials: Several pivotal clinical studies of KN046 are ongoing, including squamous non-small cell lung cancer, PD-(L)1 refractory NSCLC, pancreatic cancer, thymic carcinoma, etc. BLA is expected to be submitted in 2022.
Exploring cornerstone therapies in the post-PD-(L)1 era: 10 clinical data of KN046 presented, continuing to explore major indications, PD-(L)1 refractory and PD-(L)1 inadequate response tumors; KN046 in combination with KN026 is expected to offer a chemotherapy-free solution.
Build a core commercialization team: In 2021, the company established a core commercialization team to accelerate the commercialization of KN046 and subsequent blockbuster products.
Dr. Ting Xu, Chairman and CEO of Alphamab Oncology, commented, "2021 is the first year of the company’s commercialization. Envafolimab is the first domestic PD-L1 antibody approved for marketing in China and the world’s only subcutaneously administered PD-L1 antibody. KN046 has demonstrated excellent efficacy and potential for benefit in treating PD-(L)1 refractory and PD-(L)1 inadequate response tumors, etc. The BLA of KN046 insquamous NSCLC will be submitted soon. The pivotal phase III trials of KN046 in pancreatic cancer and PD-(L)1 refractory NSCLC have been initiated. A pivotal clinical trial of KN026, an anti-HER2 bispecific antibody, combined with chemotherapy as second-line treatment for gastric cancer has been initiated, and trials in the 1st-line and perioperative setting are under way. Data from the phase II study of KN026 combined with KN046 pave the way for further exploring chemotherapy-free regimens for HER2-positive solid tumors.

In 2021, the company has also made significant progress in our innovative R&D platform and product pipeline. We expect the innovative mechanism and preclinical efficacy of KN052 and JSKN-003 to be validated in clinical studies in 2022. Unmet medical needs, differentiation and global edge are the principles we have always adhered to.

The MRCT pivotal trial of KN046 in thymic carcinoma demonstrated our ability and confidence to develop innovative drugs to meet global health needs. Through cooperation with Pfizer, CSPC and other partners, we hope to accelerate the research and development of our candidates, and to benefit oncology patients worldwide as soon as possible.

Through the launch of Envafolimab, the company’s GMP has been fully validated. We will further expand our production capacity, improve our system, and expand our commercialization capability to lay a solid foundation for the launch of KN046 and subsequent new drugs. With 2021 already behind, we look forward a more exciting and rewarding 2022. Alphamab Oncology will stick to its vision and mission and develop steadily. We are working for more effective cancer medicines and will generate great returns for our long term shareholders.

BUSINESS HIGHLIGHTS

Since April 20, 2021, being the latest practicable date of the Company’s 2020 annual report, we have been making significant progress with respect to our product pipeline and business operations.

Product Pipeline

Our highly differentiated in-house pipeline consists of tumor monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates. Our differentiated tumor product pipeline includes one approved for marketing by the NMPA, three in late clinical stage, and two that have received IND approval or ready for IND submission.

KN046

KN046 has completed phase I clinical trials in Australia and has simultaneously been under a phase II clinical trial in the U.S. Currently, four pivotal clinical trials of KN046 in China have been launched, including two pivotal clinical trials in NSCLC, one pivotal phase III clinical trial in PDAC and one pivotal trial in thymic carcinoma. There are approximately 20 clinical trials around the world covering more than 10 types of tumors including NSCLC, triple-negative breast cancer, ESCC and thymic carcinoma. The results of these clinical trials have demonstrated a preliminary profile of good safety and promising efficacy of KN046.

Events during the Reporting Period

In April 2021, we entered into a clinical trial collaboration and supply agreement with Pfizer Inc. to evaluate the efficacy and safety of KN046 in combination with Inlyta (axitinib), for the first-line treatment of NSCLC.
We achieved positive results of KN046 with respect to its preliminary efficacy and safety in combination with nab-paclitaxel and gemcitabine as first-line treatment for unresectable locally advanced or metastatic PDAC. Such research progress was presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.
We achieved promising preliminary results in a phase II, open-label and multi-center study of KN046 in combination with chemotherapy in patients with advanced NSCLC. Such research progress was presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.
We made progress in obtaining the efficacy and safety results of KN046 plus paclitaxel/ cisplatin as first-line treatment for unresectable locally advanced, recurrent or metastatic ESCC. Such research progress was presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.
We made progress in obtaining the preliminary efficacy and safety results of a prospective phase II trial of KN046 in combination with Lenvatinib in the first-line treatment for advanced unresectable or metastatic HCC. Such research progress was presented at the ESMO (Free ESMO Whitepaper) Congress 2021.
We obtained research results of a phase II, open-label and multi-center clinical trial of KN046 in combination with platinum doublet chemotherapy as first-line treatment for advanced NSCLC harboring resistant oncogenic driver alterations. Such research results were presented at the ESMO (Free ESMO Whitepaper) Congress 2021.
In September 2021, we received an IND approval for KN046 from the NMPA for initiating a multi-center, open-label and randomized-controlled phase II/ III pivotal clinical study (ENREACH-LUNG-02/KN046-302) to evaluate the efficacy, safety and tolerability of KN046 combined with Lenvatinib versus Docetaxel in disease progression of patients with advanced NSCLC who have accepted PD-(L)1 treatment.
We achieved significant efficacy and safety results of KN046 in combination with nab-paclitaxel/gemcitabine in the first-line treatment of locally advanced unresectable or metastatic PDAC. Such results were presented at the 2021 CSCO Annual Meeting.
In September 2021, the Company entered into a partnership agreement with Hangzhou Raygene Pharmaceutical Co., Ltd. to jointly develop the combination therapy of KN046 and RG001, a proprietary anti-tumor small molecule drug, for the posterior line treatment for advanced HCC and liver metastasis colorectal cancer.
In October 2021, a multi-center, randomized, double-blind and placebo-controlled phase III clinical trial of KN046 to evaluate the efficacy and safety of KN046 in combination with the platinum-based chemotherapy in patients with advanced unresectable or metastatic squamous NSCLC, completed the enrollment of 482 patients.
In October 2021, the first patient was successfully dosed in a multi-center, open-label and randomized-controlled phase II/III pivotal clinical trial of KN046 in Mainland China, which aims to evaluate the efficacy, safety and tolerability of KN046 combined with Lenvatinib versus Docetaxel in disease progression of patients with advanced NSCLC who have accepted anti-PD-(L)1 treatment.
In November 2021, the first patient was successfully dosed in a clinical trial of KN046 in combination with ALK-1 (activin receptor-like kinase-1) antibody developed by Kintor Pharmaceutical Limited, for the treatment of advanced or refractory solid tumors.
In November 2021, the Company entered into a collaboration agreement with Guangzhou MaxiNovel Pharmaceuticals Co., Ltd., for joint clinical cooperation of MAX-40279, a multi-target tyrosine kinase inhibitor independently developed by MaxiNovel, in combination with KN046 for the treatment of gastric cancer and other indications as agreed by both parties.
In November 2021, the Company received an IND approval for KN046 from the NMPA for initiating a multi-center, randomized, double-blind and placebo-controlled phase III clinical trial to evaluate the efficacy and safety of KN046 in combination with nab-paclitaxel/ gemcitabine in the treatment of locally advanced unresectable or metastatic PDAC without systemic treatment.
In December 2021, the first patient was successfully dosed in the U.S. in an open-label and multi-center phase II pivotal clinical trial of KN046 to evaluate efficacy, safety and tolerability of KN046 in subjects with advanced thymic carcinoma.
Events after the Reporting Period and expected milestones for 2022

In February 2022, the first patient was successfully dosed in a multi-center, randomized, double-blind and placebo-controlled phase III clinical trial of KN046 to evaluate the efficacy and safety of KN046 in combination with nab-paclitaxel/gemcitabine versus placebo in combination with nab-paclitaxel/gemcitabine, in the treatment of locally advanced unresectable or metastatic PDAC without systemic treatment.
In February 2022, the Company received an IND approval from the NMPA for initiating a phase II clinical trial to evaluate the efficacy, safety, tolerability of KN046 in combination with Inlyta (axitinib) in the treatment of advanced NSCLC.
In February 2022, the Company received an IND approval from the NMPA for initiating a phase I/II clinical trial of KN046 in combination with MAX-40279, for the treatment of advanced or metastatic solid tumors.
KN046+chemo,1L sq-NSCLC: Complete the interim analysis and arrange for the BLA application as planned by mid-2022.
KN046+chemo,1L pancreatic cancer: Enroll in the majority of subjects for Phase III clinical trials.
KN046+Lenvatinib,1L HCC: Plan to start pivotal trial in 2022H2.
KN026

Events during the Reporting Period

We made advancement in evaluating the preliminary efficacy of KN026 for the treatment of HER2 expression in patients with advanced GC or GEJ. Such results were presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.
In August 2021, the first patient was successfully dosed in a phase II clinical trial of KN026 for the neoadjuvant treatment of HER2 positive early or locally breast cancer.
In August 2021, the Company received a notice of approval from the NMPA for the supplementary application for a pharmaceutical change of KN026 for clinical use, which allows KN026 liquid formulation to be used in clinical research. This is the first HER2 bispecific antibody in liquid formulation approved for conducting clinical research in China.
In August 2021, Jiangsu Alphamab Biopharmaceuticals Co., Ltd., the principal operating subsidiary wholly owned by the Company, entered into a licensing agreement with Shanhai JMT-Bio Technology Co., Ltd., a wholly-owned subsidiary of CSPC Pharmaceutical Group Limited ("CSPC"), to develop and commercialize KN026 for the treatment of breast cancer and GC in Mainland China.
We made advancement in evaluating the preliminary efficacy and safety results of KN026 in combination with KN046 in patients with HER2-positive GI tumors. Such results were presented at the ESMO (Free ESMO Whitepaper) Congress 2021.
We made progress in obtaining the preliminary safety and efficacy results of a phase II clinical trial of KN026 in combination with KN046 in patients with metastatic HER2-positive breast cancer. Such research progress was presented at the SABCS 2021.
We made progress in a phase I clinical trial of KN026 for the treatment of patients with HER2-positive metastatic breast cancer. Such research progress was presented at the SABCS 2021.
Events after the Reporting Period and expected milestones for 2022

In January 2022, the Company received an IND approval from the NMPA for initiating a randomized and multi-center phase II/III clinical trial of KN026 to evaluate the efficacy and safety of KN026 combined with chemotherapy in patients with HER2-positive GC (including GEJ) who have failed first-line treatment.
In January 2022, the phase II clinical trial of KN026 combined with KN046 in the treatment of HER2-positive solid tumors, successfully completed patient enrollment. The interim analysis is expected to be conducted in the second quarter of 2022.
In February 2022, data from a phase I clinical study of the KN026 for the treatment of HER2-positive metastatic breast cancer were published in Clinical Cancer Research, a journal published by the American Association for Cancer Research (AACR) (Free AACR Whitepaper).
In March 2022, the preliminary results of phase II clinical trial of KN026 in combination with KN046 for the treatment of locally advanced unresectable or metastatic HER2-positive solid cancer were accepted for e-poster presentation at the 2022 AACR (Free AACR Whitepaper) annual meeting.
KN046+KN026, Chemo-free, HER2+1L GC: Start the pivotal trial in 2022Q2.
KN035 (Envafolimab)

Events during the Reporting Period

In June 2021, the study design of the ENVASARC pivotal trial conducted in the U.S. for KN035 was presented by TRACON in a poster session at the 2021 ASCO (Free ASCO Whitepaper) annual meeting.
In June 2021, the U.S. FDA has granted orphan drug designation (ODD) to KN035 for the treatment of patients with soft tissue sarcoma. This is the second ODD for KN035 after the first ODD in advanced biliary track cancer and the fourth ODD that we obtained from the FDA.
In September 2021, we obtained an IND approval from the NMPA for KN035 in combination of Lenvatinib for the treatment of patients who have failed or are intolerant of platinum containing chemotherapy and are not suitable for radical treatment with locally advanced metastatic or recurrent non-microsatellite instability-high phenotype/non-DNA deficient mismatch repair endometrial cancer.
In November 2021, we obtained formal conditional approval from the NMPA for marketing KN035 (Envafolimab). The approval is for the treatment of MSI-H or dMMR advanced solid tumors.
In December 2021, the Company, 3D Medicines and Simcere, jointly announced that the first batch of prescriptions for KN035 (Envafolimab), the world’s first subcutaneously injected PD-L1 antibody, has been implemented across China.
KN019

The phase II clinical trial of KN019 for the treatment of rheumatoid arthritis completed the patient enrollment. The final analysis of clinical results is expected to be completed in the first half of 2022.
In 2021, we initiated a clinical study on the bioavailability of KN019 in the switch from intravenous infusion to subcutaneous administration.
KN052

In February 2022, the Company received an IND approval for KN052 from the NMPA for initiating a phase Ia/Ib clinical trial to evaluate the safety, tolerability, pharmacokinetics/ pharmacodynamics, and antineoplastic activity of KN052 in the treatment of advanced solid tumors.
JSKN-003

The Company completed the efficacy validation and process development for JSKN-003 in June 2021 and targets to submit IND application in the second quarter of 2022.
Manufacturing Facilities

The facility of Jiangsu Alphamab is designed to house over 40,000L production capacity in total. We obtained a drug production license for the phase I-(1) of our new manufacturing facilities from Jiangsu Drug Administration, on July 6, 2020. Phase I-(2), including product workshop, pilot plant and R&D center, is under construction and expected to be put into operation in the first half of 2022; Phase I-(3) of our new manufacturing facilities has started construction.

Other Highlights

In May 2021, Jiangsu Alphamab entered into a collaboration agreement with Suzhou Alphamab Co., Ltd. for two technology development projects, namely, JSKN003 and the preparation process development project for mGalt1, a key material of conjugation process, and KN062 COVID-19 neutralizing bispecific antibody development project.
In December 2021, the Company was listed as one of the 2021 Top 100 Chinese Pharmaceutical Innovative Enterprise. The Company has been acknowledged as such for the third consecutive year.
In January 2022, the Company was awarded "The Most Valuable Pharmaceutical and Medical Company" award at the Sixth Golden Hong Kong Stocks Awards ceremony.
Financial Summary

For the year ended December 31, 2021，we recorded total revenue of RMB146.0 million. The Group mainly generates revenue from (i) sales of pharmaceutical product; (ii) royalty income; (iii) license fee income; and (iv) goods or consumables for R&D projects.
For the year ended December 31, 2021, the Group’s other income decreased by RMB64.1 million to RMB47.0 million, as compared to RMB111.1 million for the year ended December 31, 2020.
For the year ended December 31, 2021, our R&D expenses increased by RMB150.2 million to RMB481.4 million, compared to RMB331.2 million for the year ended December 31, 2020, primarily due to (i) the increase in the number of ongoing clinical trials; (ii) the expansion of the scale of our clinical studies; (iii) the advancement of clinical trials of our drug candidates; and (iv) the increase in staff cost due to the increase in our R&D staff.

On March 29, 2022 Keen Eye, a leading AI company in digital pathology for clinical research and Ultivue, Inc. an industry leader in multiplexing tools and novel image analysis solutions for tissue biomarker studies, reported a collaborative agreement to promote multiplexed immunofluorescence (mIF) assays and scalable AI applications to unlock spatial analysis in clinical research (Press release, Ultivue, MAR 29, 2022, View Source [SID1234611142]).

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Ultivue develops unique solutions for use in mIF applications, imaging and spatial phenomics. Its proprietary InSituPlex technology enabling improved signal to noise data is designed for fast and comprehensive exploration of biologically relevant targets, up to 12-plex, with same slide-H&E analysis in tissue samples. This technology combines the power of computational pathology & spatial biology to guide translational science in immuno-oncology.

Ultivue recognizes the need for dedicated and custom AI models to analyze the complexity of mIF data at scale and to provide improved turn-around times and consistent readouts across large cohorts "We are looking forward to accelerating data generation for biopharma customers from mIF kits by partnering with Keen Eye. We can jointly support more scalable workflows which will allow us to meet increasing demand in clinical trials." said Florian Leiss, Ph.D. Vice President Digital Health Strategies at Ultivue.

Keen Eye is an AI Platform company dedicated to deliver accurate, standardized, and undiscovered tissue insights in research and clinical development using Deep Learning histopathology digital image analysis. Its proprietary models dedicated for spatial exploration of tumor microenvironment give access to reliable tissue segmentation, biomarker quantification, cell population profiling, and morphological discovery.

Thanks to Ultivue’s pre-optimized assays, the high accuracy achieved for every biomarker will drastically reduce errors during quantification steps as phenotypes combine several biomarkers. As Dr. Sylvain Berlemont, Keen Eye’s founder and CEO says, "We are thrilled to expand our application portfolio combined with best-in-class Ultivue mIF assays to biopharma companies and CROs. This partnership will undeniably support our customers to fully extend reproducibility and scalability throughout their clinical research.".

On March 29, 2022 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic and medical imaging applications, reported a corporate update highlighting progress across its key programs during the past twelve months, and upcoming milestones (Press release, NorthStar Medical Radiostopes, MAR 29, 2022, View Source [SID1234611141]).

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"NorthStar has made tremendous strides in advancing our portfolio over the past year and we are very excited about the future," said Stephen Merrick, President and Chief Executive Officer of NorthStar Medical Radioisotopes. "Our plans to ensure reliable, environmentally friendly, non-uranium based radioisotope supply for the United States continue to progress. RadioGenix System (technetium Tc 99m generator) utilization is increasing. We are well on our way to having dual production and processing pathways for Mo-99 to ensure additional domestic capacity and supply security to best meet customer demand. Our Mo-99 facility expansions are nearing completion and moving to the final phase of activities required for licensure and FDA approval.

Mr. Merrick continued, "NorthStar is rapidly expanding its leadership position in the emerging area of therapeutic radiopharmaceuticals by defining the supply chain for commercial-scale, reliable and environmentally preferred therapeutic radioisotope production. Using electron accelerator technology, we are well-positioned to be the first commercial-scale producer of copper-67 (Cu-67) and actinium-225 (Ac-225). We have built out the production space and ordered processing equipment for Cu-67 production. Cu-67, given its clean manufacturing process, allows for high volume production, with no issues associated with access to stable target material or generation of long-lived radioactive waste. NorthStar is further investing in the future with a first-of-its-kind Actinium-225 Production facility, exclusively dedicated to commercial-scale production of our no-carrier added (n.c.a.) Ac-225. Illustrating NorthStar’s commitment to commercial-scale manufacture of this isotope, a third Rhodotron TT-300 HE accelerator was ordered from IBA in November 2021.

"During the year, we expanded our SPECT pipeline through an agreement with GE Healthcare to manufacture and distribute iodine-123 capsules for imaging of thyroid cancer and other diseases, to be available pending appropriate licensure and FDA approval, which is expected in early 2023. FibroScint, a novel cardiovascular SPECT imaging agent, is advancing towards exploratory IND-enabling studies, and NorthStar is collaborating with Monopar Therapeutics to develop a targeted Ac-225 based radiotherapeutic agent for cancer and severe COVID-19. We continue to evaluate additional potential opportunities with specialized SPECT radiopharmaceuticals and therapeutic radioisotopes to address unmet healthcare needs. NorthStar anticipates sustained progress and growth as we expand our horizons and execute strongly in our mission to provide patients with global access to our game-changing radiopharmaceuticals."

A deep commitment to environmentally responsible radioisotope production
NorthStar is committed to ensuring that health systems have access to innovative, clean solutions that minimize the environmental footprint of their nuclear medicine departments. All NorthStar processes are non-uranium based and employ the Company’s "Reduce, Recover, Reuse" approach for reliable, domestic and environmentally sound medical radioisotope production. The Company continues to set leadership standards for domestic, environmentally sound radioisotope production across its portfolio to meet the needs of health systems and patients.

NorthStar’s unique production technology for Mo-99 offers a highly differentiated environmental advantage over traditional uranium-based methods. This results in comparatively benign, short-lived and easily managed waste streams, in contrast to uranium-based methods that result in highly radioactive, long-lived waste with significant burdens to global waste streams.
Like all NorthStar processes, electron accelerator production of Mo-99, Ac-225 and Cu-67 radioisotopes is non-uranium based and highly efficient. For example, the Rhodotron accelerator uses significantly less electricity when compared to older linear accelerators.
NorthStar is utilizing environmentally preferred production technology for its high purity non-carrier-added (n.c.a.) Ac-225. Electron accelerators will produce n.c.a. Ac-225 that is free of long-lived radioactive contaminants and byproducts associated with many other production methods, which pose regulatory and waste management challenges for hospitals and health systems.
Northstar’s production of Cu-67 is both high volume and highly sustainable, allowing for the direct substitution of reactor-based therapeutic isotopes such as lutetium-177. The process is highly efficient with no associated long-lived radioactive contaminants.
Corporate development and industry leadership
NorthStar is firmly positioned for sustained long term growth and increasing global industry prominence.

New executives

Frank Scholz, Ph.D., was appointed as NorthStar’s Senior Vice President and Chief Operating Officer. Dr. Scholz has extensive operational experience in the pharmaceutical and life sciences industries, and will help lead the next phase of NorthStar’s growth. With oversight of the Company’s Strategic Execution, Regulatory Affairs, Engineering & Technology, Manufacturing Operations & Supply Chain, and Advanced Radioisotope & Therapeutic Technologies teams, he will be instrumental in driving NorthStar’s initiatives across its portfolio.
NorthStar appointed Adam D. Lynch as Vice President, Corporate Development and External Affairs. Mr. Lynch’s deep experience in healthcare, business and finance will help progress NorthStar’s corporate development efforts. His initial focus is to work with health systems so that they can realize the economic and social benefits of using domestically produced medical radioisotopes that are manufactured in a way that minimizes environment impact.
Industry leadership

In August 2021, NorthStar was awarded $37 million in new cooperative agreement funds with the U.S. Department of Energy’s National Nuclear Security Administration (DOE/NNSA) as part of an industry outreach initiative to establish reliable domestic Mo-99 production without the use of highly enriched uranium (HEU). NorthStar is the first and only company to achieve commercialized Mo-99 production through collaboration with the DOE/NNSA. With inclusion of the current and past awards, NorthStar has been awarded a total of over $100 million in cooperative agreement funds by DOE/NNSA.
NorthStar is widely recognized for its leadership position in radioisotope technology development and commercialization and the nuclear medicine industry.
In June 2021, NorthStar hosted an Industry User Meeting in conjunction with the Society of Nuclear Medicine and Molecular Imaging (SNMMI), "Accelerating the Future of Nuclear Medicine: Advances in Radioisotope and Therapeutic Technologies." In addition, NorthStar President and Chief Executive Officer Stephen Merrick also participated in a CEO Summit and Panel discussion, "The Potential, Promise and Future of Therapeutics."
Commercial U.S. Mo-99 manufacturing and production expansion
Currently, and for more than three years, NorthStar remains the only commercialized U.S. producer of Mo-99. The Company is aggressively expanding and establishing environmentally sound 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 Beloit, Wis., Accelerator Production facility expansion will ensure additional Mo‑99 capacity, enable flexible production scheduling, including Sunday production, and minimize customer supply risks.
In April 2021, NorthStar announced a major milestone in its efforts to expand U.S. production capacity for Mo-99 with the delivery of two custom-built IBA Rhodotron TT 300-HE (High Energy) electron beam accelerators at its facility in Beloit, Wis.
In January 2022, NorthStar announced that both of its Rhodotron TT 300-HE electron beam accelerators achieved full beam energy of 40 MeV, validating its approach for commercial-scale production. Equipment testing is underway, with commercial production expected early in 2023, pending appropriate licensure and FDA approval.
NorthStar’s Beloit, Wis., Isotope Processing facility will complement current Columbia processing capacity for Mo-99 source vessels. The facility will enable NorthStar to more than double its current Mo-99 processing capabilities.
Equipment testing and validation are underway, with commercial production planned for early 2023, pending appropriate licensure and FDA approval.
As part of NorthStar’s "Reduce, Recover, Reuse" initiative, the facility houses a reclamation suite, featuring proprietary technology to recover and purify either Mo-98 or Mo-100 source material, which are reused to manufacture new targets that will be irradiated to produce Mo-99.
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. Ongoing product development programs continue to maximize operational utility and efficiency of RadioGenix Systems in producing Tc-99m, and include plans for next generation Tc-99m production.

RadioGenix Systems have generated well over one million doses of Tc-99m for patients’ diagnostic imaging studies to date, with utilization continuing to steadily increase. 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.
In March 2022, NorthStar and RLS (USA) Inc. expanded their supply agreement to provide RLS’ nationwide radiopharmacy network with additional domestically-produced Mo-99. RLS plans to install additional RadioGenix Systems in its radiopharmacies, increasing availability of NorthStar’s non-uranium Mo-99. The agreement is part of both companies’ shared commitment to broaden access to reliable, environmentally sound Mo-99/Tc-99m, to help health systems and the RLS nationwide radiopharmacy network meet corporate sustainability objectives.
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 deliver therapeutic doses of radiation to destroy cancer cells in patients with serious disease while sparing healthy tissue. Development of Ac-225 based therapies has been severely constrained by limitations in current production technology and very limited supply. Development of Cu-67 has also been historically hampered by the lack of commercial chelators to securely hold copper without leaking it in vivo, which limited demand for the isotope. The recent development of Clarity Pharmaceuticals’ Targeted Copper Theranostics platform using chelators that are able to securely hold copper is now reaching later stage development and commercialization, driving Cu‑67 demand.

NorthStar is applying its commercial-scale radioisotope production experience with Mo-99 to provide reliable Ac-225 and Cu-67 supply to advance clinical research and for commercial radiopharmaceutical products. The Company is leveraging technology expertise demonstrated by the successful launch of the RadioGenix System and non-uranium based Mo-99 supply, as well as key learnings from sophisticated techniques required in constructing its advanced Accelerator Production and Isotope Processing facilities.
In November 2021, NorthStar announced a contract with IBA to purchase a third Rhodotron TT300 HE electron beam accelerator, exclusively dedicated for Ac-225 production. The accelerator will be built in parallel with construction of NorthStar’s Actinium-225 Production facility.
In September 2021, NorthStar broke ground on its first-in-kind Actinium-225 Accelerator Production facility. Construction has begun as of mid-March, 2022, and initial production of radiochemical grade Ac-225 planned for late 2023. A Drug Master File will be submitted to the FDA in mid-2024, which, upon FDA acceptance, will allow NorthStar to provide cGMP grade Ac‑225.
NorthStar has multiple supply agreements already in place to provide clinical trial supply and commercial-scale quantities of Ac-225 and Cu-67, and expects additional supply agreements during 2022.
In March 2022, NorthStar and Convergent Therapeutics signed a supply agreement for NorthStar’s high purity non-carrier-added (n.c.a.) Ac-225. Convergent will use NorthStar’s Ac-225 to radiolabel its lead asset, CONV01-α, a prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody, currently being investigated as a treatment for prostate cancer.
In September 2021, NorthStar and POINT Biopharma signed a supply agreement under which NorthStar will provide POINT with its n.c.a. Ac-225. POINT will use NorthStar’s Ac‑225 in investigational studies of PNT2001, a next-generation Prostate-Specific Membrane Antigen (PSMA) for non-metastatic castrate-sensitive prostate cancer (nmCSPC); PNT2004, a Fibroblast Activation Protein-α candidate with potential pan-cancer applications; and to advance its novel Tumor Microenvironment (TME) tumor-targeting technology platform.
In May 2021, NorthStar and Clarity Pharmaceuticals entered into an exclusive U.S. supply agreement for Cu-67, for the supply of Cu-67 towards Clarity’s Targeted Copper Theranostics programs to treat neuroblastoma, breast and prostate cancers, among others. NorthStar anticipates that production of radiochemical grade Cu-67 will begin in late 2022.
Other supply agreements have been signed, but not disclosed, under confidentiality agreements with NorthStar pharmaceutical partners.
NorthStar and Monopar Therapeutics continue their collaboration on Ac-225-labeled MNPR-101, an investigational diagnostic and therapeutic radiopharmaceutical for cancer and severe COVID-19. In May 2021, the companies announced filing of two provisional patents relating to a unique and highly efficient chelating technology. Pathways to initiating a first-in-human clinical study are currently being evaluated.
NorthStar is evaluating additional potential opportunities for the production and commercialization of other novel radioisotopes to support the needs of researchers and pharmaceutical drug developers.
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. A Phase 2 SBIR funding submission is planned for Q4 2022, with an exploratory Investigational New Drug (IND) filing for a Phase 1 study planned for early 2023.
In June, 2021, NorthStar expanded its pipeline through an exclusive U.S. manufacturing and distribution agreement with GE Healthcare to produce and distribute iodine-123 (I-123) capsules. I-123 is the proven radiopharmaceutical standard in diagnostic imaging studies for thyroid disease. GE Healthcare’s Pharmaceutical Diagnostics unit will manufacture and supply NorthStar with I-123 capsules under the NorthStar label using a new, state-of-the-art production system. Upon regulatory approvals, NorthStar will retain exclusive U.S. marketing and distribution rights for I-123 capsules in 100 µCi and 200 µCi formulations. FDA approval is expected in early 2023.
NorthStar is evaluating additional potential opportunities in specialized SPECT radiopharmaceuticals to address unmet healthcare needs and synergies with its product portfolio.
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 that negatively impacted patient health care. 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

INDICATION
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.
Sodium Pertechnetate Tc 99m Injection contributes to a patient’s long-term cumulative radiation exposure. Ensure safe handling to protect patients and health care workers from unintentional radiation exposure. Use the lowest dose of Sodium Pertechnetate Tc 99m Injection necessary for imaging and ensure safe handling and preparation to protect the patient and health care worker from unintentional radiation exposure. Encourage patients to drink fluids and void as frequently as possible after intravenous or intravesicular administration. Advise patients to blow their nose and wash their eyes with water after ophthalmic administration.
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.
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. Follow step-by-step instructions for use provided in the Operator’s Guide, RadioGenix System 1.2.

On March 29, 2022 BioCurity is a private preclinical biotech company developing supportive cancer oncology drugs to prevent or mitigate some of the side effects of radiation therapy for cancer patients (Press release, BioCurity Pharmaceuticals, MAR 29, 2022, View Source [SID1234611140]). BioCurity reported the Company received a notice of allowance of claims from the United States Patent and Trademark Office for the Company’s United States patent that covers the use of the Company’s cerium oxide nanoparticles for the reduction of side effects caused by radiation therapy for lung and pancreatic cancer patients receiving a combination of radiation therapy and chemotherapy as part of their treatment regimen .

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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

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This new patent builds upon the 8 US patents BioCurity exclusively controls related to its novel drug development. BioCurity also exclusively controls its international patents, which currently exist in Australia, China, Europe, Hong Kong, Japan, and Mexico, and cover the use of the Company’s cerium oxide nanoparticle technology for patients with certain cancers treated with radiation combined with chemotherapy.

Globally, it is estimated that 6 million of the 18 million annually diagnosed new cancer patients receive radiation. The short and long-term side effects of radiation therapy to various organs and tissues in humans have been well characterized, can impair a cancer patient’s medical treatment plan, and can leave cancer survivors with permanent adverse conditions. Treatment of these side effects cost more than 3 billion dollars annually in the US. The global cancer supportive care market is projected to reach approximately 41 billion dollars by 2027 and is driven by the growing prevalence of cancer.

"BioCurity’s scientific discovery in an IV formulation for internal tissue as well as a topical formulation to protect against skin damage offers the potential to prevent the often-devastating side effects associated with radiation therapy and to enhance the treatment outcomes for patients undergoing radiation therapy alone or in combination with chemotherapy to treat their cancer. Each of the formulations have been studied in various proof of concept animal models of head and neck, lung, breast, pancreatic, colorectal, and prostate cancer. The positive preclinical data in these animal models suggest the potential use in multiple types of cancers where radiation therapy is used alone or in conjunction with chemotherapy to treat cancer patients," said Dr. Cheryl Baker PhD, Scientific Co-Founder, and a Board member of BioCurity.

BioCurity’s clinical development team led by CSSi LifeSciences has an excellent track record in working with small and emerging biopharmaceutical companies to advance their lead drug products to and through commercialization. With 100% success in obtaining an Investigational New Drug and 500 successful drugs, diagnostics and devices commercialized.

On March 29, 2022 Cytonus Therapeutics Inc. (Cytonus), a biotechnology company developing therapeutic products for targeted delivery in vivo, reported that their CSO, Dr. Richard Klemke Ph.D., will present the preclinical progress made on Cytonus’ lead Cargocyte product candidates at the annual AACR (Free AACR Whitepaper) meeting in New Orleans (Press release, Cytonus Therapeutics, MAR 29, 2022, View Source [SID1234611139]).

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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

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Cargocytes armed with interleukin 12 (CA-IL-12) can be engineered to actively home, migrate, and penetrate deep into specific disease foci and synthesize biologically active therapeutic within the target tissues, hours after intravenous administration.

Dr. Klemke will share data demonstrating striking infiltration of engineered Cargocytes into solid tumors in in vivo models of metastatic Triple Negative Breast Cancer (TNBC), localizing and synthesizing the company’s proprietary Interleukin twelve (IL-12) construct. Furthermore, Dr. Klemke will share in vivo data demonstrating the efficacy of tumor-localized activity of CA-IL-12 in reducing tumor burden, particularly in combination with immune checkpoint inhibitors.

Abstract #3519: Bioengineering enucleated cell vehicles for targeted delivery of Interleukin 12 to metastatic tumors.

These results highlight the capabilities of Cytonus’ innovative Cargocyte platform in addressing solid tumor penetration challenges. Importantly, Cargocytes offer localized delivery of potent immunotherapies in a controlled manner to enhance their safety profile.

"While immunocytokine therapeutics can modulate the immune system, systemic delivery often results in adverse events and toxicity which limits their clinical utility. What is remarkable about our data is that we demonstrate a historically toxic cytokine (IL-12) can be localized to metastatic sites with exquisite accuracy and without systemic off-target effects. Our unique approach leads to a substantial reduction in metastatic burden and as such has potential to treat patients with late-stage cancers," said Dr. Remo Moomiaie-Qajar, M.D. co-founder and CEO of Cytonus Therapeutics.

"Arguably the most exciting discovery in immune oncology in the past decade has been the development of immune checkpoint inhibitors (ICI). Unfortunately, only 13% of all patients respond to ICI therapy. Our data clearly demonstrates the ability of CA-IL-12 to make recalcitrant tumors (TNBC) responsive to ICI therapy. These promising findings demonstrates the enabling nature of CA-IL-12 to expand the utility of ICI to the large number of cancer patients normally refractory to this approach," said Dr. Moomiaie-Qajar, M.D.

About Cargocyte

Cargocyte products are derived from enucleated cell lines and are uniquely engineered with specific disease targeting molecules to safely transport therapeutic payloads intravenously and deep into difficult-to-reach target tissues. Cargocytes can deliver and actively produce the therapeutic agent of choice on-site in a controlled, predictable, and safe manner. The proprietary Cargocyte technology is a first-in-class therapeutic platform with numerous potential medical applications across unmet therapeutic areas. Cytonus is developing a broad and deep pipeline of bioengineered Cargocytes for targeted delivery of a wide range of therapeutic modalities including Protein, Peptides, RNAs, ASOs, small molecule drugs, viruses, and gene editing agents.