On March 31, 2021 Race Oncology Limited ("Race") reported to update our shareholders on progress of our clinical and preclinical programs under the Three Pillars strategy, originally outlined at the Annual General Meeting of shareholders on 30 November 2020 (Press release, Race Oncology, MAR 31, 2021, View Source [SID1234577555]). Today’s update confirms committed and planned programs to maximise the significant opportunity offered by Bisantrene as both a targeted precision oncology drug and as a differentiated chemotherapeutic, with the objective of delivering better therapeutic outcomes for patients.

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Pillar 1 – FTO (Fat mass and obesity associated protein), a transformative opportunity
At the 2020 AGM Race announced its Pillar 1 program focused on Bisantrene’s ability to act as a potent inhibitor of FTO, a protein understood to play a key central role in the proliferation of many cancers. Two clinically relevant proof-of-concept cancer indications were identified, melanoma and clear cell renal cell carcinoma (ccRCC). Our intention was to undertake preclinical studies in both these indications to support the initiation of FTO-directed Phase I/II clinical trials in CY 2022.

FTO-directed melanoma pre-clinical study
In March 2021 Race announced that renowned melanoma cancer researchers, Professor Xu Dong Zhang and Associate Professor Lei Jin of the University of Newcastle would undertake a collaborative preclinical melanoma research program (ASX announcement: 19 March 2021).

The program’s purpose is to explore the use of Bisantrene as a novel FTO-directed treatment for melanoma using cellular and mouse models to identify drug combinations that improve melanoma treatment, with a focus on treatment resistant cancers. Previous independent published studies have observed that FTO is overproduced in approximately 50% of metastatic melanoma cancers and that the inhibition of FTO can overcome PD-1 immune checkpoint inhibitor resistance in mouse models of melanoma.

This preclinical project will report results over the coming 12 months, which will be shared with the market as received. The results of this study will support a Phase II FTO-directed human trial of Bisantrene in melanoma, currently scheduled to begin in Australia in CY 2022.

FTO-directed clear cell Renal Cell Carcinoma pre-clinical (ccRCC) study
In March 2021 Race announced eminent cancer researcher, Associate Professor Nikki Verrills, who successfully ran Race’s preclinical breast and ovarian cancer programs, would undertake a collaborative preclinical ccRCC-focused research program (ASX announcement: 25 March 2021).

The purpose of this research program is to use cellular models to explore the potential to use Bisantrene as a FTO-directed treatment of ccRCC, a devastating form of kidney cancer. Previous studies have observed that FTO enzyme activity is essential for ccRCC cell survival and the inhibition of FTO can directly kill more than 90% of ccRCC cancers.

The results of this study will support a Phase II FTO-directed human trial of Bisantrene in ccRCC patients, currently scheduled to begin in Australia in CY 2022. This preclinical project will report results over the coming 12 months, which will be shared with the market as received.

Other activities
Race is exploring the initiation of a Phase I dose escalation clinical safety trial of Bisantrene in CY 2021, directed at showing its capacity to inhibit FTO in patients with advanced cancers. Founded upon supportive data, such a trial could accelerate the Phase II proof-of-concept trials planned for CY 2022. Race will update the market on the progress of this proposal once finalised.

Pillar 2 – Breast Cancer and Bisantrene as a differentiated chemotherapeutic
In December 2020 Race tasked the clinical research organisation (CRO), George Clinical, with advisement on an optimal clinical trial design for the Pillar 2 breast cancer program (ASX announcement: 26 November 2020). After extensive consultation with Race’s clinical management team, George Clinical, and key opinion leaders (KOLs) in the breast cancer space, together with data from Race’s recent preclinical breast cancer program (ASX announcements: 24 November 2020 and 9 March 2021), a two-path clinical program has been developed.

Australian Phase II trial in late-stage metastatic breast cancer patients
The first path involves initiation of a Phase II clinical trial of Bisantrene in late-stage metastatic breast cancer patients (who have had three or more lines of prior therapy) in Australia, leveraging Race’s recent preclinical data that demonstrated Bisantrene can kill breast cancer cells resistant to current standard-of-care drugs. These data support the potential clinical utility of Bisantrene in treating late-stage breast cancer patients with treatment resistant tumours.

A Principal Investigator (PI) has been recruited to run this Phase II trial and advanced preparation for this trial has been completed including trial design, synopsis generation, CRO selection, patient inclusion/exclusion criteria, budgeting, and clinical trial site selection.

Final contract signing and initiation of this trial is expected to be completed in Q2 CY 2021 and patient treatment is expected to begin in the second half of CY 2021. Further updates to the market on this trial program will be made over CY 2021.

European Phase IIb trial in anthracycline-naïve metastatic breast cancer patients
Discussions with key opinion leaders in the breast cancer field identified an important clinical need to further demonstrate the historical heart safety of Bisantrene in a modern treatment environment if Bisantrene is to be used as a frontline replacement for the current cardiac muscle-damaging anthracycline chemotherapeutics. Patient exposure to anthracyclines can result in both acute cardiac muscle damage at the time of treatment, as well as a delayed damage response that can take months or even years to manifest1. To provide robust data on cardiac safety it is essential that Bisantrene is trialled in a patient population that has not been previously exposed to anthracycline chemotherapeutics. Such a patient population is not recruitable in Australia. Initial research has identified Eastern Europe as being able to provide anthracycline treatment naïve breast cancer patients.

After detailed discussion with a number international breast cancer KOLs, George Clinical has been tasked by Race with developing and costing a Phase IIb double-blinded clinical trial of Bisantrene verses doxorubicin in geographies where anthracycline naïve patients can be recruited.

George Clinical will provide a detailed, costed proposal to enable gated decision making around the potential to run such a Phase IIb clinical study. This report is expected within three months and Race will update the market once received.

1Kimmick, G., Dent, S., & Klem, I. (2019). Risk of Cardiomyopathy in Breast Cancer: How Can We Attenuate the Risk of Heart Failure from Anthracyclines and Anti-HER2 Therapies? Current Treatment Options in Cardiovascular Medicine, 21(6), 30.

Other Activities
Race is exploring low-cost collaborative preclinical studies focused on understanding the molecular mechanism of action of Bisantrene’s heart safety profile. Advanced discussions are underway with a leading Australian team specialising in anthracycline cardiotoxicity research. Race expects to update the market on the outcome of these discussions in early Q2 CY 2021.

Pillar 3 – Acute Myeloid Leukaemia (AML), an FDA approval pathway
Significant progress has been made on the Pillar 3 program during the quarter. Race has committed in principle support to initiate in 2021 two Phase I/II clinical trials in relapsed/refractory acute myeloid leukaemia (r/r AML) in Australia and Israel. In addition, significant progress has been made in exploring the potential use of Bisantrene in paediatric AML that may enable Race to generate the required data needed for award of a Paediatric Priority Review Voucher (ASX announcement: 18 July 2018). Previous vouchers have been sold on the secondary market for between US$80 and US$200 million.

Phase I/II clinical trial of Bisantrene in combination with Clofarabine and Fludarabine in relapsed or refractory AML (Israel)
Race has reached in principle agreement with Prof Nagler of the Chiam Sheba Medical Center to undertake an open label Phase I/II combination clinical trial of Bisantrene in r/r AML patients.
Prof Nagler led the Phase II single agent open label r/r AML trial of Bisantrene which reported a 40% clinical response rate in a very difficult to treat population of r/r AML patients (ASX announcement: 16 June 2020).

This Phase I/II trial will enrol 29 patients and involve the use of Bisantrene in combination with the nucleoside analogues, clofarabine and fludarabine. Unpublished preclinical data from Professors Andersson and Valdez of the MD Anderson Cancer Clinic in Houston, Texas has identified strong synergistic killing of AML cells using this three-drug combination.

Human ethics approval for this trial has been granted and the first patient is expected to be treated in Q2 CY 2021. The trial is scheduled to run for up to 36 months, but Race will release progress updates on patient responses as they are received.

Trial contract details are currently being finalised and Race expects to sign in early Q2 CY 2021.

Phase I/II Clinical Trial of Bisantrene in Extramedullary AML (Australia)
Race has reached in principle agreement with Associate Professor Anoop K Enjeti, Director of Haematology at the Calvary Mater Newcastle and John Hunter Hospitals, to undertake an open label Phase I/II clinical trial of Bisantrene in patients with the extramedullary form of AML. Extramedullary AML occurs when the leukaemia spreads from the bone marrow and forms solid tumours in tissues such as the skin, breast, kidney, brain, or other organs. A 2020 prospective positron imaging trial identified that up to 22% of AML patients have the extramedullary form.

Dr Enjeti is a highly experienced clinical haematologist having designed and led more than 25 clinical trials. Dr Enjeti is the co-chair of the MDS/AML working party for the Australasian Lymphoma and Leukemia Group (ALLG) for Cooperative Clinical trials. He has published more than 45 papers in the haematology field and attracted more than $3.5 million in grant funding.

This two-armed Phase I/II trial will involve the use of Bisantrene as a high dose single agent treatment of extramedullary AML patients able to endure high intensity chemotherapy, or alternatively as a low dose Bisantrene treatment in combination with a hypomethylating agent in the less fit patients. The trial will recruit 40 patients at 10 clinical sites across Australia and New Zealand.

The trial is expected to received human ethics approval in Q3 CY 2021 and treat the first patient in late 2021. The trial is expected to run for 18 months. Results of this trial will support parallel pivotal Phase II/III clinical trials in the USA and EU with the aim of achieving rapid FDA/EMA label approval of Bisantrene for use in r/r AML. Furthermore, this trial may be expandable into a paediatric extramedullary AML population and enable Race to receive a US Paediatric Priority Review Voucher.

Phase I/II clinical trial of Bisantrene in combination with Fludarabine and Cytarabine for children with r/r AML (USA)
Race is in advanced evaluation on the prospect of initiating a pivotal Phase I/II trial of Bisantrene in combination with fludarabine and cytarabine in children with first or second relapse of AML. In principle support has been received from the USA Children’s Oncology Group (COG) and a proposed trial design has been provided to Race by COG for evaluation. The trial is expected to run for 36 months and requires FDA IND approval before it can be initiated.

While this trial may enable Race to meet the conditions required to be granted a Paediatric Priority Review Voucher, additional research and communication with the FDA is required to determine if the trial can be completed before the September 2026 sunset of the Rare Paediatric Disease Voucher program. Race will update the market as to the outcome of this research when complete.

Preclinical Extramedullary AML Study
In March 2021 Race announced Associate Professor Nikki Verrills, would undertake a collaborative preclinical extramedullary focused research program (ASX announcement: 30 March 2021).

The aim of this project is to support the clinical use of Bisantrene as a novel treatment for extramedullary AML, a difficult to treat form of AML, using an extramedullary mouse model developed by A/Prof Verrills’ team.
The results of this study will provide support for a pivotal (Phase II/III) trial of Bisantrene in extramedullary AML patients with the aim of providing a rapid path to FDA approval for Bisantrene as an orphan drug under the 505(b)(2) track.

This project is to start immediately with the results expected to be reported over the coming 12 months.

"Following on from the November 2020 AGM, we have evaluated how to best maximise the exceptional asset that Bisantrene represents. The 2021 program capitalises on Bisantrene’s significant FTO opportunity while also pursuing its differentiated chemotherapy profile. We propose that the strategy outlined today minimises risk while maximising commercial and therapeutic upside, particularly with respect to the potential we see in FTO. The 2021 committed program is fully funded and will generate actionable data by year-end, so supporting an expanded 2022 clinical program thereafter."

Chief Executive Officer, Mr Phillip Lynch and Chief Scientific Officer, Dr Daniel Tillett
Shareholders can expect continued updates to results as they read out, and in later 2021 specific communication on expanded FTO-focused clinical programs.

On March 31, 2021 Nascent Biotech, Inc. (OTCQB:NBIO) ("Nascent Biotech," "Nascent," or the "Company"), a clinical-stage biotechnology company pioneering the development of monoclonal antibodies targeting treatment of various cancers and viral infections, reported that patients have been enrolled and initial dosing has begun in the Company’s landmark Phase I trial to evaluate Pritumumab ("PTB") as a treatment option for Brain Cancer, including Malignant Primary Brain Tumors and adult Brain Metastases (Press release, Nascent Biotech, MAR 31, 2021, View Source [SID1234577413]).

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Patient enrollment remains open, and the trial continues to recruit new patients for participation. Those interested may review trial requirements HERE.

"Dosing human cancer patients in our Phase 1 clinical trial is a key milestone on the path toward determining the safety profile of Pritumumab under clinical conditions," noted Nascent CEO Sean Carrick. "This study will also provide fresh insight into PTB’s efficacy on primary brain tumors."

PTB is a natural human antibody that works by binding to cell surface Vimentin (also referred to as ectodomain vimentin, or EDV), a protein expressed on the surface of epithelial cancers. PTB is used as a targeted immunotherapy that, unlike chemotherapy, targets only cancer cells without damaging healthy ones. Because of this dynamic, the current clinical study may have implications for future research on PTB as a treatment option for a broad range of more common cancers, including breast, colon, and lung.

On March 31, 2021 BridgeBio Pharma, Inc. (Nasdaq: BBIO), through its affiliate QED Therapeutics, Inc., and Helsinn Group reported a global collaboration and licensing agreement (the "Agreement") to further develop and commercialize QED Therapeutics’ FGFR1-3 inhibitor, infigratinib, in oncology and all other indications except for skeletal dysplasias (including achondroplasia) (Press release, BridgeBio, MAR 31, 2021, View Source [SID1234577440]). Completion of the Agreement is subject to regulatory review and customary closing conditions, which are expected to occur in the second quarter of 2021.

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Infigratinib is an orally administered, ATP-competitive, tyrosine kinase inhibitor that is designed to inhibit FGFR, and being investigated for treatment of individuals with FGFR-driven conditions, including cholangiocarcinoma (bile duct cancer), urothelial carcinoma (urinary tract and bladder cancer), and other FGFR-driven cancers.

Under the terms of the Agreement, BridgeBio will retain all rights to infigratinib in skeletal dysplasia, including achondroplasia. Subject to U.S. Food and Drug Administration ("FDA") approval, QED and Helsinn will co-commercialize infigratinib in oncology indications in the U.S. and will share profits and losses on a 50:50 basis. Helsinn will have exclusive commercialization rights and lead commercialization for infigratinib in non-skeletal dysplasia indications outside of the U.S., excluding China, Hong Kong and Macau, which are covered by BridgeBio’s strategic development and commercialization collaboration with LianBio. Under the Agreement, BridgeBio will be eligible to receive more than $2 billion in upfront, regulatory and commercial milestones, as well as tiered royalties on adjusted net sales from Helsinn Group.

"We are privileged to partner with Helsinn as we strive to unlock the full potential of infigratinib for patients with FGFR-driven cancers," said BridgeBio CEO and founder Neil Kumar, Ph.D. "Helsinn has an impressive track record of advancing and commercializing oncology therapies around the globe. Our hope is that partnering with Helsinn will significantly strengthen our anticipated upcoming launch of infigratinib and our ongoing research into infigratinib’s potential across other cancer indications."

Riccardo Braglia, Helsinn Group Vice Chairman and CEO, commented, "As a leader in oncology therapeutics and supportive care, Helsinn is always looking to partner with high quality companies. The combination of BridgeBio and its lead oncology product candidate, infigratinib, fall into the strategic sweet spot of a quality company and product with which we look to work. We are highly excited by the potential positive impact this collaboration can deliver for patients around the world."

BridgeBio and Helsinn Group intend to pursue an ambitious co-development plan in oncology indications, including clinical investigation underway in first-line cholangiocarcinoma and adjuvant urothelial cancer. This plan will be underpinned by close collaboration among the parties, with the aim of developing new treatments for patients with FGFR-driven cancers. As infigratinib heads toward potential approval and commercialization in a range of oncology indications, Helsinn’s unique integrated licensing business model will enable its distribution to reach patients globally.

The FDA has accepted the New Drug Application ("NDA") for infigratinib for patients with previously-treated advanced cholangiocarcinoma ("CCA") harboring an FGFR2 gene fusion or rearrangement. The NDA has been granted Priority Review designation and is being reviewed under the Real-Time Oncology Review ("RTOR") pilot program, an initiative of the FDA’s Oncology Center of Excellence designed to expedite the delivery of safe and effective cancer treatments to patients. Additionally, infigratinib is currently under review in Australia and Canada under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence that allows for concurrent submission and review of oncology drugs among participating international regulatory agencies.

On March 31, 2021 CTI BioPharma Corp. (Nasdaq: CTIC) ("CTI"), a biopharmaceutical company focused on the acquisition, development and commercialization of novel targeted therapies covering a spectrum of blood-related cancers, reported the pricing of its previously announced underwritten public offering of 14,260,800 shares of its common stock and 600 shares of its series X1 preferred stock (the "Series X1 Preferred") (Press release, CTI BioPharma, MAR 31, 2021, View Source [SID1234577458]). In addition, CTI has granted the underwriters a 30-day option to purchase up to an additional 2,139,120 shares of its common stock on the same terms and conditions. The offering price to the public of a share of common stock is $2.50 and the offering price to the public of a share of Series X1 Preferred Stock is $25,000. Each share of Series X1 Preferred will be convertible into 10,000 shares of common stock at the election of the holder, subject to beneficial ownership conversion limits applicable to the Series X1 Preferred.

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All of the securities in the offering are being sold by CTI. The gross proceeds to CTI from this underwritten public offering are expected to be approximately $50.7 million, before deducting the underwriting discount and other estimated offering expenses payable by CTI. The offering is expected to close on or about April 6, 2021, subject to the satisfaction of customary closing conditions.

CTI intends to use the proceeds from the proposed sale of its shares of common stock and Series X1 Preferred Stock for commercialization activities for pacritinib, general working capital and corporate purposes.

Stifel and JMP Securities are acting as joint book-running managers for the offering. BTIG is acting as lead manager for the offering.

The offering is being made pursuant to a registration statement on Form S-3 that was previously filed with the U.S. Securities and Exchange Commission (the "SEC") and subsequently was declared effective by the SEC. A preliminary prospectus supplement and accompanying base prospectus relating to and describing the terms of the offering has been filed with the SEC and a final prospectus supplement relating to the offering will be filed with the SEC and will be available on the SEC’s web site at www.sec.gov. When available, copies of the final prospectus relating to these securities may be obtained by sending a request to Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery St, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720 or by email at [email protected], or JMP Securities LLC, 600 Montgomery St, Suite 1100, San Francisco, CA 94111, Attn: Prospectus Department, telephone: 415-835-8900.

This press release does not constitute an offer to sell or the solicitation of an offer to buy any of these securities, nor will there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On March 31, 2021 BeyondSpring Inc. (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, reported the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and the China National Medical Products Administration (NMPA) for use of plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN) (Press release, BeyondSpring Pharmaceuticals, MAR 31, 2021, View Source [SID1234577501]). Plinabulin in combination with a G-CSF therapy, which received breakthrough therapy designation from the U.S. FDA and the China NMPA for "concurrent administration with myelosuppressive chemotherapeutic regimens in patients with non-myeloid malignancies for the prevention of CIN," has the potential to raise the standard of care in CIN for the first time in 30 years.

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CIN remains a severely unmet medical need. 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 agent seeking FDA approval that has the potential to fill this gap by working in Week 1 to prevent the onset and progression of CIN. Therefore, 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.

"CIN is a major concern for physicians and their patients undergoing cancer treatment. Plinabulin provides benefits above and beyond what is currently available on the market and has the potential to be a game-changer for patients undergoing chemotherapy treatment," said Dr. Douglas Blayney, Professor of Medicine at Stanford University Medical School and global PI for CIN studies. "CIN, which can lead to life-threatening infections, is the number one reason for the 4D’s in chemotherapy (Decrease, Delay and Discontinue dose and Downgrade regimen). We hope plinabulin will allow patients to better tolerate chemotherapy, thus enabling patients to stick to their optimal treatment plan and avoid serious CIN complications."

The NDA submission is based on positive data from BeyondSpring’s PROTECTIVE-2 Phase 3 registration study which showed that plinabulin in combination with pegfilgrastim demonstrated superior CIN prevention benefit, compared to pegfilgrastim alone. The study met the primary endpoint, with a statistically significant improvement in the rate of prevention of grade 4 neutropenia (improved from 13.6% to 31.5%, p=0.0015) and met all key secondary endpoints, including duration of severe neutropenia (DSN) and absolute neutrophil count (ANC) nadir. In addition, the combination reduced clinical complications such as incidence and severity of febrile neutropenia (FN) and incidence and duration of hospitalization for FN patients. The combination is well tolerated, with an over 20% reduction of grade 4 Treatment-Emergent Adverse Events (TEAE) in the combination compared to that of pegfilgrastim alone. The NDA submissions will include five supportive trials that show consistent CIN prevention in various chemotherapy regimens and cancers in over 1,200 patients.

"This NDA submission is the culmination of years of research to prove that plinabulin can improve the long-established standard of care and address an unmet medical need to further alleviate the risk burden of CIN for patients receiving chemotherapy," said Dr. Lan Huang, co-founder, CEO, and chairman of BeyondSpring. "With CIN responsible for potentially delaying treatment and causing life-threatening infections, we hope that receiving the improved care represented by the plinabulin and G-CSF combination will allow patients to better tolerate chemotherapy and potentially see increased treatment success rates. We are grateful for the patients’ participation in plinabulin’s clinical trials and the participation and contributions of our investigators and our many other clinical partners."

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 febrile neutropenia, or "FN"), which necessitates ER/hospital visits. 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 who may benefit from treatment with plinabulin, if approved, to approximately 440,000 cancer patients in the U.S. annually.

There is a large unmet medical need and a growing market for CIN prevention and treatment in China as well. According to Lancet Oncology, 60% of East Asia cancer patients are treated with chemotherapy1. In 2020, there were 4.6 million new cancer patients in China which could correspond to 2.8 million patients using chemotherapy and needing CIN prevention agents. According to IQVIA data, the G-CSF drug market (for CIN treatment) in China is growing at over 30% a year.

About PROTECTIVE-2 (Study 106) Phase 3 Registration Study
The Phase 3 portion of PROTECTIVE-2 was a double-blind and active-controlled global registration study. It was designed as a superiority study to compare the safety and efficacy of plinabulin (40 mg, Day 1 dose) + pegfilgrastim (6 mg, Day 2 dose) versus a single dose of pegfilgrastim (6 mg, Day 2 dose) in patients with breast cancer, treated with docetaxel, doxorubicin and cyclophosphamide (TAC, Day 1 dose) in a 21-day cycle. TAC is an example of high FN risk chemotherapy and is the regimen used in all G-CSF biosimilar registration studies.

The primary endpoint was the rate of prevention of Grade 4 neutropenia and secondary endpoints included DSN and mean ANC nadir in Cycle 1. Literature shows that despite the use of pegfilgrastim, 83 to 93 percent of patients treated with TAC still suffer Grade 4 neutropenia (or rate of Grade 4 neutropenia prevention at 7-17%), which demonstrates the severe unmet medical need for improved treatment2,3.

The ANC data, which are used to calculate these endpoints, were obtained through central laboratory assessments by Covance Bioanalytical Methods using standardized and validated analytical tests. Covance was the clinical contract research organization (CRO) for patient recruitment and monitoring of global sites for this study.

About CIN
Chemotherapy-induced neutropenia (CIN) is the primary dose-limiting toxicity in cancer patients who receive chemotherapy and is the primary cause for the 4D’s (Decrease, Delay, Discontinue dose and Downgrade regimen). The 4D’s lead to a decrease of the anti-cancer benefit of chemotherapy, e.g., >15% of dose reduction correlated to >50% survival reduction4. The National Comprehensive Cancer Network (NCCN) recently updated its treatment guidelines for CIN prophylaxis using G-CSFs to include both high- and intermediate-FN risk patients treated with chemotherapies, to preserve hospital and ER resources for COVID-19 patients, and to maximize protection from CIN. The NCCN’s action effectively doubled the number of patients recommended to receive CIN prophylaxis.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immune-modulating microtubule-binding agent (SIMBA). A global Phase 3 clinical trial in CIN (PROTECTIVE-2) with plinabulin in combination with pegfilgrastim versus pegfilgrastim alone has been completed and is the basis for an NDA filing in the U.S. and China for the prevention of CIN. In this trial, plinabulin reduced the "neutropenia vulnerability gap" associated with G-CSF therapy alone. Additionally, a global Phase 3 study for the treatment of later-stage NSCLC in EGFR wild-type patients (DUBLIN-3) is now fully enrolled and will evaluate the combination of plinabulin and docetaxel versus docetaxel alone for overall survival in NSCLC patients. 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 cells5,6 and the second is early-onset action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs)7. Effects on HSPCs could explain the potential for plinabulin not only to prevent CIN but also to increase circulating CD34+ cells in patients. 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.