On December 1, 2021 BeyondSpring Pharmaceuticals (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, reported it has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) seeking approval of plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN) (Press release, BeyondSpring Pharmaceuticals, DEC 1, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-pharmaceuticals-receives-complete-response-letter-from-the-fda-for-plinabulin-new-drug-application-for-prevention-of-chemotherapy-induced-neutropenia-cin [SID1234596319]). The FDA issued the CRL to indicate that they have completed their review of the application and have determined that it cannot be approved in its present form.

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The FDA’s CRL indicated that the results of the single registrational trial (106 Phase 3) was not sufficiently robust to demonstrate benefit and that a second well controlled trial would be required to satisfy the substantial evidence requirement to support the CIN indication.

"BeyondSpring strongly believes that plinabulin in combination with G-CSF has significant potential to raise the standard of care in CIN, a devastating side effect of chemotherapy," said Dr. Lan Huang, BeyondSpring’s co-founder, chief executive officer and chairwoman. "The Company plans to request a meeting with the FDA and remains committed to its goal of bringing plinabulin to cancer patients in need globally."

BeyondSpring remains confident in the efficacy and safety data for plinabulin in combination with G-CSF for the prevention of CIN. The Company expects to work closely with the FDA to consider the possible future clinical pathway for CIN, which may include a second study.

Plinabulin is the first drug candidate submitted for FDA approval that has the potential to work in the critical first week of chemotherapy treatment before G-CSF is effective, to prevent the onset and improve clinical outcomes of CIN.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected, NDA-stage asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. 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 of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation and priority review from both U.S. and China FDA for the 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 December 1, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that the Company has initiated a Phase 2, single arm, open-label study of trilaciclib in patients with early-stage triple negative breast cancer (TNBC) designed to further investigate the role of trilaciclib in modulating the anti-tumor immune response (Press release, G1 Therapeutics, DEC 1, 2021, View Source [SID1234596317]). Pathologic complete response endpoints are also being evaluated in this trial. Initial results of this study are expected in the second half of 2022.

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"Data from our Phase 2 TNBC trial of trilaciclib in combination with chemotherapy showed clinically meaningful and substantial improvements in overall survival as well as enhanced measures of immune system function compared to chemotherapy alone," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "Those preliminary data support the important role trilaciclib may play in treating cancer by enhancing T cell activation and favorably altering the tumor microenvironment. This Phase 2 clinical study will support trilaciclib’s mechanistic effects potentially responsible for enhanced anti-tumor immune responses in patients and generate important data that will help guide our future development decisions across additional tumor types and new treatment combinations."

Patient recruitment in this trial is now underway. Approximately 30 patients will be enrolled in this Phase 2 multicenter, open-label, single-arm, neoadjuvant study. Up to three tumor tissue samples will be collected for assessment. Tumor tissue will be obtained at baseline prior to study drug administration. Patients will receive a single dose of monotherapy trilaciclib, followed by a tumor biopsy approximately one week later. Following the biopsy, patients will enter the treatment phase in which trilaciclib will be administered on Day 1 of each cycle of anthracycline/cyclophosphamide for four cycles followed by trilaciclib administered on Day 1 of each weekly cycle of taxane chemotherapy for 12 cycles. Immune checkpoint inhibitor and/or carboplatin may be added to therapy at the discretion of the investigator. Three to five weeks after the last dose of chemotherapy, patients will proceed to surgery at which time a third tumor tissue sample will be collected if the patient has residual disease.

Study treatment will continue as per protocol to completion or early discontinuation of chemotherapy, until unacceptable toxicity, Investigator’s decision to withdraw the patient from study treatment, consent withdrawal, or the end of the study, whichever occurs first.

The primary objective is to evaluate the immune-based mechanism of action of trilaciclib after a single-dose as measured by the change in the ratio of CD8+ tumor-infiltrating lymphocytes (TILs) to regulatory T cell (Tregs) in the tumor microenvironment. Key secondary and exploratory endpoints include:

Assessment of pathologic complete response (pCR) rate at the time of definitive surgery.
Evaluation of the safety and tolerability of trilaciclib in combination with standard neoadjuvant systemic therapies.
Tumor mRNA analyses and immunohistochemistry and peripheral blood immune profiling following trilaciclib.
Identification of molecular and cellular biomarkers in tumor or blood samples that may be indicative of clinical response/resistance, pharmacodynamic activity, and/or the mechanism of action of trilaciclib and other systemic treatments.
About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15-20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because mTNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with mTNBC compared to other forms of breast cancer, and mTNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.

On December 1, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported it has completed its share purchase agreement to acquire 100 percent of the outstanding shares of TIB Molbiol Group (Press release, Hoffmann-La Roche, DEC 1, 2021, View Source [SID1234596316]). TIB Molbiol will continue to operate as a subsidiary within the Diagnostics division. Roche and TIB Molbiol will build on their capabilities for the rapid development of assays for emerging pathogens and potential health threats, such as infectious diseases.

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With over 45 CE-IVD assays and more than a 100 research-use-only assays joining the Roche family, the companies will jointly accelerate access for patients around the world to even more clinically important diagnostic tests. TIB Molbiol will further expand Roche’s molecular diagnostics solutions, especially for the flexible open platforms LightCycler PCR and MagNA Pure sample preparation systems.

The two companies have collaborated for more than 20 years to rapidly address critical healthcare needs including biological threats, such as SARS, anthrax, avian influenza virus H5N1, MERS, the novel influenza virus H1N1 swine, Ebola virus, Zika virus and most recently, SARS-CoV-2 virus and its variants. For example, in 2001 with anthrax and 2003 with SARS-CoV1, TIB Molbiol demonstrated their ability to develop PCR assays for the detection of new pathogens within days.

"I am very pleased that together with TIB Molbiol, we can significantly improve access for patients to a broader spectrum of diagnostic tests – from high volume routine tests to the diagnosis of rare diseases. TIB Molbiol will continue to be an innovation engine and frontrunner in our common fight against infectious diseases, such as SARS-CoV-2", said Thomas Schinecker, CEO Roche Diagnostics. "TIB Molbiol has helped to shape the future of PCR infectious disease testing, and will continue to drive cutting-edge research so we can bring better healthcare outcomes to patients faster."

On December 1, 2021 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or the "Company"), an Australian-based clinical stage radiopharmaceutical company developing next-generation products to address the growing need in oncology, reported that 15 of 30 participants have been recruited in the diagnostic 64Cu SAR-bisPSMA clinical trial (PROPELLER) in patients with untreated, confirmed prostate cancer, scheduled for radical prostatectomy (Press release, Clarity Pharmaceuticals, DEC 1, 2021, View Source [SID1234596315]).

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68Ga PSMA-11 (~200MBq, left) vs. 64Cu SAR-bisPSMA (~200MBq, right) in the same patient; time between serial imaging was 8 days. Standardised Uptake Value (SUVmax)* of the lesions were 6.5 and 6.3 for 68Ga PSMA-11 and 16.5 and 18.5 for 64Cu SAR-bisPSMA

*SUV is a measurement of product uptake in tissue normalised to a distribution volume

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are excited to have quickly and successfully recruited half of the patients planned for the PROPELLER trial with all three sites actively recruiting and imaging prostate cancer patients across Australia. We have been able to not only generate strong preliminary clinical data since the trial commencement in July 2021, but also validate our on-demand distribution model where the 64Cu-SAR-bisPSMA has been shipped to the trial sites across Australia from a central manufacturing facility with minimal delays or interruptions. The pace and quality of work that we were able to achieve during this trial is reflective of the appetite for the new generation of radiopharmaceuticals that can cater to large indications in the oncology space and shift the radiopharmaceutical field towards the "big pharma" model with central manufacture of ready-to-use products. This shift has potential to significantly improve patient care by focusing on the needs of patients and enable their treating staff to access critical treatments that are safe and efficacious, on time and at any treatment centre with a positron emission tomography (PET) camera."

The PROPELLER trial is a Phase I Positron Emission Tomography (PET) imaging trial of participants with confirmed prostate cancer using 64Cu SAR-bisPSMA. It is a 30-patient multi-centre, blinded review, dose ranging, non-randomised study of 64Cu-SAR-bisPSMA administered to patients with confirmed prostate cancer prior to radical prostatectomy (NCT04839367)1. The main goals of the PROPELLER trial are to:

Determine the safety and tolerability of 64Cu SAR-bisPSMA in participants with untreated, confirmed prostate cancer and planned for radical prostatectomy;
Examine 64Cu SAR-bisPSMA at different dose levels;
Determine the ability of 64Cu SAR-bisPSMA to detect primary prostate cancer; and
Compare diagnostic properties of 64Cu SAR-bisPSMA against 68Ga PSMA-11, the standard of care for prostate cancer imaging in Australia.
Prof Louise Emmett (St Vincent’s Hospital Sydney), Principal Investigator in the PROPELLER trial commented, "The preliminary data from the patients imaged in the PROPELLER trial to date looks very promising as it supports the evidence of higher uptake of 64Cu SAR-bisPSMA in the tumours that has been shown in the pre-clinical studies. Higher uptake in the tumours means that they are more visible on the PET scans and hence have a higher chance of being detected. These initial results are encouraging for further development of this product as a diagnostic, and the higher uptake and retention also make it an exciting therapeutic target with 67Cu. In addition to the anticipated clinical benefits, having access to centrally manufactured products has the potential to improve patient care by providing an alternative to currently used short-lived diagnostic radioisotopes, such as 68Ga and 18F, the production of which can pose challenges in delivering critical imaging scans to patients with cancer on time. I am very pleased to be working with Clarity on the Targeted Copper Theranostics (TCT) platform of products, having recently completed the C-BOBCAT trial of SAR-Bombesin, in hopes that these products will improve the current treatment paradigm for oncology patients."

Dr Alan Taylor further commented, "Clarity is well on track to explore and validate the benefits of the TCT platform, including the logistical, manufacturing and treatment benefits associated with the "perfect pairing" of copper-64 and copper-67. These benefits hold promise of providing a large patient population with early, accurate and precise detection of prostate cancer. As such, we look forward to recruiting the remaining 50% of patients and generating more data to validate the compelling results from our preclinical studies as well as the exciting preliminary results from the PROPELLER trial and our US-based 64/67Cu SAR-bisPSMA theranostic trial (SECuRE trial (NCT04868604)2) in pursuit of our ultimate goal of improving treatment outcomes for children and adults with cancer."

This announcement has been authorised for release by the Executive Chairman.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide3. In 2021, the National Cancer Institute estimated 248,530 new cases of prostate cancer in the US and around 34,130 deaths from the disease4. Annually, there are around ~34,000 men in the US who are diagnosed with mCRCP5, ~90% of whom have tumours which express PSMA6.

On December 1, 2021 EpiAxis Therapeutics reported that among the first batch of companies that will present at Wholesale Investor’s fifth annual Emergence 2022 event in March (Press release, EpiAxis Therapeutics, DEC 1, 2021, View Source;utm_medium=rss&utm_campaign=epiaxis-presents-emergence-2022 [SID1234596314]).

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It’s the first time the event has been held live in two years. The annual Emergence event brings together high-growth companies from fintech, renewable energy, biotech and ecommerce to showcase their investment opportunities. Companies included in the first announcement alongside EpiAxis include SelfWealth, Novapep, Long Pipes, EG Funds and Horizon 3 Biotech.

"We are delighted to be part of this group announcement with Wholesale Investor and look forward to presenting EpiAxis at the event, sharing our progress on the development of novel therapeutics for metastatic disease," said EpiAxis CEO Dr Jeremy Chrisp.

Wholesale Investor events have connected $187million of capital in just under four years, showcased to more than 29,000 high net-worth investors and investment groups at events spanning nine countries and 12 cities. EpiAxis became part of the investment platform in October. Our membership kicked off with Dr Chrisp presenting at Wholesale Investor’s STEM 2021 Conference. It was a valuable opportunity to network with investors interested in biotech and discuss how our epigenetic science aims to maintain and extend cancer remission, with low side effects

Emergence 2022 will be held from March 9-11, 2022. Click here to book tickets to the event.