On June 8, 2021 BeyondSpring Inc. (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, reported a late-breaking poster presentation of the company’s lead asset plinabulin, a selective immunomodulating microtubule-binding agent (SIMBA), in combination with pegfilgrastim in breast cancer as part of the Phase 3 PROTECTIVE-2 chemotherapy-induced neutropenia (CIN) study, at the Federation of Clinical Immunology Societies (FOCIS) Annual Meeting being held from June 8-11, 2021 (Press release, BeyondSpring Pharmaceuticals, JUN 8, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-announces-a-late-breaking-poster-presentation-of-protective-2-phase-3-data-showing-plinabulin-in-combination-with-pegfilgrastim-reverses-the-immune-suppressive-effects-of-pegfilgrastim [SID1234585695]).

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BeyondSpring’s poster titled "Adding Plinabulin (Plin) to Pegfilgrastim (Peg) Reverses the Immune Suppressive Potential of Peg while Offering Superior Prevention of Chemotherapy Induced Neutropenia (CIN) versus Peg Alone)," will be presented on June 9, 2021 at 3:15 p.m. PDT and authors will be available at the poster reception on June 10, 2021 from 4:45 p.m. – 5:30 p.m. PDT (Poster number TH58). Plinabulin in combination with pegfilgrastim demonstrated a superior immune profile and CIN prevention outcomes for patients treated with plinabulin in combination with pegfilgrastim compared to pegfilgrastim alone in breast cancer patients dosed with TAC (Taxotere, doxorubicin, and cyclophosphamide) in PROTECTIVE-2 Phase 3 study. Compared to pegfilgrastim alone (n=110), the plinabulin and pegfilgrastim combination (n=111) showed decreased production of immature neutrophil band (p=0.0012), and decreased promyelocytes and myelocyte production (p=0.0488). Immature neutrophil band and promyelocytes and myelocytes are less functional defending against infection and have potentially deleterious immune suppression effects.

"Plinabulin has broad effects on the immune system and tumor microenvironment. We are excited to see that in addition to the well-demonstrated CIN prevention benefits, we also see that plinabulin can protect against some of the immune-suppressive side effects of pegfilgrastim," said Ramon Mohanlal M.D., Ph.D., Chief Medical Officer and Executive Vice President of Research and Development at BeyondSpring "Plinabulin is a pipeline-in-a-drug and we are seeing more evidence of this with every study, demonstrating that it can help patients with cancer, from side-effects to cancer treatment."

The Company has submitted New Drug Applications (NDA) for plinabulin in combination with pegfilgrastim as a treatment for the prevention of CIN for review in both the U.S. and China. The U.S. FDA accepted the NDA with Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) action date of November 30, 2021.

About The Federation of Clinical Immunology Societies (FOCIS) Annual Meeting
The Federation of Clinical Immunology Societies (FOCIS) exists to improve human health through immunology by fostering interdisciplinary approaches to both understand and treat immune-based diseases. The Federation of Clinical Immunology Societies is a key forum where opinion leaders come together to chart the path to the next major breakthrough in disease therapy. Through FOCIS, researchers and clinicians share knowledge across traditional disease borders, and identify commonalities between treatments and therapies that are life-changing for those impacted by immune-mediated diseases. Initially established as a cross-disciplinary meeting, FOCIS held its first Annual Meeting in 2001. After two successful consecutive meetings, FOCIS incorporated as a 501(c)3 organization in 2003. Today, FOCIS has 58 Member Societies, representing roughly 65,000 clinician scientists.

About CIN
CIN remains a severely unmet medical need and is the primary cause for the 4D’s (Decrease, Delay, Discontinue dose and Downgrade regimen) that compromise carefully selected cancer treatment regimens. Treatment or prevention of CIN with G-CSF has been the standard of care since Neupogen was approved in 1991. The main benefit of G-CSF treatment, however, is in Week 2 after chemotherapy. Week 1 after chemotherapy is considered the "neutropenia vulnerability gap" where over 75% of CIN-related clinical complications occur, including febrile neutropenia, infection, hospitalization and death. Plinabulin is the first drug seeking FDA approval that has the potential to fill this gap. Combining plinabulin and G-CSF may maximize the protection of patients for the full cycle of chemotherapy, as demonstrated in the PROTECTIVE-2 Phase 3 registration study.

Each year in the U.S., 110,000 patients receiving chemotherapy are hospitalized after developing CIN, a severe side effect that increases the risk of infection with fever (also called FN). Due to the COVID-19 pandemic, the updated National Comprehensive Cancer Network (NCCN) guidelines expanded the use of prophylactic G-CSFs, including pegfilgrastim, from high-risk patients only (chemo FN rate >20%), to include intermediate-risk patients (FN rate between 10-20%), to reduce the number of hospital/ER visits related to CIN. The revision of the NCCN guidelines effectively increases the addressable market of patients to approximately 467,500 cancer patients in the U.S. annually.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA). It is a novel, intravenous infused, patent-protected, NDA ready asset for CIN prevention indication and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC). Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received breakthrough designation from both US and China FDA for CIN prevention indication. As a "pipeline in a drug," plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody resistant patients.

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 Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals reported presentations at the upcoming Society of Nuclear Medicine and Molecular Imaging Annual Meeting (SNMMI), to be held in a virtual format from June 11 to 15, 2021 (Press release, Blue Earth Diagnostics, JUN 8, 2021, View Source [SID1234583721]). Results to be presented include an interim analysis of the comparative diagnostic performance of Axumin (fluciclovine F 18) PET in biochemical recurrence of prostate cancer, an evaluation of its impact on patient management in oligometastatic disease, and its performance in patients with recurrent prostate cancer who have suffered multiple treatment failures, among others. Details of the presentations to be given by Blue Earth Diagnostics collaborators are listed below. Additionally, the Company will host a satellite symposium, "The Role of PET in Post-Prostatectomy Radiotherapy," which will review the role of PET in guiding management decisions and influencing treatment outcomes and results of the EMPIRE-1 randomized trial.

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NOTE: Axumin (fluciclovine F 18) injection is FDA-approved for PET imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

Highlighted Axumin (Fluciclovine F 18) Scientific Presentations

All SNMMI presentations are available beginning Friday, June 11, 2021.

Title:

Positivity rates of 18F-fluciclovine PET/CT and 68Ga-PSMA PET/CT: Interim analysis of a secondary endpoint from a randomized trial
in patients with biochemical recurrence post-prostatectomy

Author(s):

Olayinka Abiodun-Ojo, Ashesh Jani, Omotayo Adediran, Akinyemi Akintayo, Bridget Fielder, Subir Goyal, Raghuveer Halkar and David Schuster

Session:

Poster – Physician/Pharm

Abstract:

1130

Title:

Incidence and Impact of Oligometastatic Disease Detected on 18F-Fluciclovine PET/CT in Biochemically Recurrent Prostate Cancer

Author(s):

Redmond-Craig Anderson, Erik Velez and Hossein Jadvar

Session:

Poster – Physician/Pharm

Abstract:

1332

Title:

Diagnostic Performance of F-18 Fluciclovine PET/CT in Prostate Cancer Patients with rising PSA Level < =0.5 ng/ml after multiple
treatment failures

Author(s):

Ajalaya Teyateeti, Achiraya Teyateeti, Gregory Ravizzini, Guofan Xu, Chad Tang, Shi-Ming Tu, Homer Macapinlac and Yang Lu

Session:

Poster – Physician/Pharm

Abstract:

1361

Title:

Single atypical metastases from Prostate Cancer as detected with Fluciclovine PET/CT: A Pictorial Essay

Author(s):

Amer Alassi, Peter Temsah, Leonard Goldfarb, Razi Muzaffar and Medhat Osman

Session:

Poster – Educational Exhibits

Abstract:

2042

Title:

Blanching defects at the pressure points: a potential pitfall in dynamic Total-Body PET/CT studies

Author(s):

Kristin McBride, Edwin Leung, Heather Hunt, Mike Nguyen, Benjamin Spencer, Simon Cherry, Ramsey Badawi, Lorenzo Nardo and Yasser Abdelhafez

Session:

Oral – Technologist

Abstract:

186

Blue Earth Diagnostics invites participants at the 2021 SNMMI Annual Meeting to attend the presentations above and to visit the Company’s virtual Commercial Exhibit Booth. Blue Earth Diagnostics also has a Medical Affairs information booth at SNMMI, where attendees can learn about ongoing clinical trials. The Company is also hosting a Satellite Symposium, "The Role of PET in Post-Prostatectomy Radiotherapy," with invited speaker Dr. Ashesh Jani, MD, MSEE, FASTRO, James C. Kennedy Professor, Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Ga. The symposium will be held on Saturday, June 12, 2021, from 11:45 a.m. – 12:45 pm ET. For more information about the meeting, please see the SNMMI online program here. Information on abstract presentations is available here.

U.S. Indication and Important Safety Information About Axumin

INDICATION
Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full U.S. Axumin prescribing information is available at:

View Source

About Axumin (fluciclovine F 18)
Axumin (fluciclovine F 18) injection is a novel product indicated for use in positron emission tomography (PET) imaging to identify suspected sites of prostate cancer recurrence in men. Recurrence of prostate cancer is suspected by an increase in prostate specific antigen (PSA) levels following prior treatment. PET imaging with Axumin may identify the location and extent of such recurrence. Axumin was developed to enable visualization of the increased amino acid transport that occurs in many cancers, including prostate cancer. It consists of a synthetic amino acid that is preferentially taken up by prostate cancer cells compared with surrounding normal tissues and is labeled with the radioisotope F 18 for PET imaging. Fluciclovine F 18 was invented at Emory University in Atlanta, Ga., with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences. Axumin was approved by the U.S. Food and Drug Administration in May 2016, following Priority Review, and is the first product commercialized by Blue Earth Diagnostics, which licensed the product from GE Healthcare. The molecule is being investigated by Blue Earth Diagnostics for other potential cancer indications including in neuro-oncology.

On June 8, 2021 Pascal Biosciences Inc. ("Pascal" or the "Company") (TSXV:PAS) (OTC:PSCBF), reported that it has been awarded a grant of US$343,750 from the National Cancer Institute of the US National Institutes of Health (NIH) (Press release, Pascal Biosciences, JUN 8, 2021, View Source [SID1234583740]). This two-year award will fund development of Pascal’s antibody drug for Acute Lymphoblastic Leukemia (ALL), which is the most common childhood leukemia.

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Pascal is the first to advance an antibody targeting the highly leukemia-specific protein, VpreB, for treating ALL. "This grant validates our scientific efforts and will accelerate development of a new treatment for leukemia patients", stated CEO Patrick Gray. "The exquisite specificity of our antibody will eliminate many of the hazards of current therapies for ALL. This grant will enable Pascal to bring our product into clinical trials."

More than 6000 patients are diagnosed with Acute Lymphoblastic Leukemia (ALL) each year in Canada and the US. About half of ALL patients are adults and half are children, which makes this disease the most common type of childhood leukemia. Pascal’s drug will be eligible for orphan drug designation, which can enable financial incentives and a seven year marketing exclusivity. Pascal has filed for patent protection for its ALL treatment. While the number of patients with ALL is relatively small, the market potential for Pascal’s drug could be significant. Other cancer products for orphan diseases have proven to be financially successful, selling over $1B each year.

ABOUT ACUTE LYMPHOBLASTIC LEUKEMIA

ALL arises as a consequence of dysregulated proliferation of early-stage B cells. The current treatment for ALL—a chemotherapeutic regimen with four toxic drugs—has not changed in over 40 years. This regimen can be quite effective (85% success in children, 50% in adults). However, short- and long-term side effects can be devastating: young patients may have cognitive or developmental problems and frequently develop additional cancers 20 years after treatment, while older patients tend to have great difficulty coping with side effects. Pascal is developing monoclonal antibodies specific for a cell surface protein found only on ALL cells and on the early-stage cells from which ALL originates. This specificity spares the normal, mature B lymphocytes needed for protecting the patient from infection. Pascal’s lead antibody for drug development binds the tumor target with high affinity and has good biophysical properties for expedient drug development. Patients treated with Pascal’s drug will have the benefit of a highly targeted treatment and will also avoid the detrimental side effects of chemotherapy. The NIH grant, which covers both research and administrative costs for Pascal’s program over a period of two years, will validate a drug product for clinical development to treat this challenging leukemia.

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

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

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

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

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

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

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

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

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

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

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

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

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

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