On December 18, 2019 BeyondSpring Inc. (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, reported an update on the Company’s operations and announced its financial results for the three months ended September 30, 2019 (Press release, BeyondSpring Pharmaceuticals, DEC 18, 2019, View Source [SID1234552462]).

"We are pleased with the progress we are seeing in our clinical programs surrounding our lead compound, Plinabulin, for the treatment of non-small cell lung cancer (NSCLC) and CIN," said Dr. Lan Huang, BeyondSpring’s Co-Founder, Chairman and Chief Executive Officer. "Our goal from day one has been to develop transforming treatments for cancer patients. Between the enrollment of the first patient in our global Phase 3 Study 106, the publication of Plinabulin’s immune mechanism as a potent Antigen Presenting Cell (APC) inducer in three peer-review journals and continual positive data being presented at medical meetings world-wide, we remain on track to address large unmet medical needs among these cancer patients."

"The combination of our clinical experience – over 900 patients enrolled globally – and the deep insight into Plinabulin’s immune mechanism – a potent APC inducer – lead us to believe Plinabulin has potential to be a ’pipeline in a drug’. Our life cycle plan for Plinabulin begins with the foundational indications in NSCLC and CIN. From here we expect to expand into a broader chemotherapy combination footprint, and eventually we expect to transform Plinabulin’s potential in combination with checkpoint inhibitors and radiation or chemotherapy. This triple therapy combination could be a powerful treatment in multiple cancer types with significant market opportunities," added Dr. Huang. "We anticipate filing NDAs for Plinabulin in the U.S. and China for both NSCLC and CIN over the next 18 months. The success of our recent round of financing ensures that we will have the necessary resources to achieve the clinical milestones moving forward."

Recent Operational Highlights

Novel Study Design of Plinabulin in NSCLC Phase 3

In October 2019, BeyondSpring announced that its abstract, titled, "DUBLIN-3, a Stage IIIb / IV NSCLC Phase 3 Trial Comparing the Plinabulin / Docetaxel Combination with Docetaxel Alone," was presented at this year’s European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The abstract highlighted the study’s unique design, which positively addressed the challenges associated with trial failure risk in NSCLC studies.

In November 2019, BeyondSpring presented a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, titled, "Validation of a Single-Blinded (Patients Only) Study Design for the Prevention of Premature Patient Consent Withdrawal in the Immuno-Oncology Trial DUBLIN-3." This abstract explained that cancer patients generally prefer immunotherapy over chemotherapy, which can lead to premature withdrawal of their consent to participate in a clinical trial if they are allocated to the chemotherapy comparator arm, and can negatively impact the study’s outcome. Specifically, the DUBLIN-3 trial was a single-blinded study, while the Javelin trial was an open-label study, which led investigators to their conclusion.

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Plinabulin’s Superior Profile in CIN Prevention

In September 2019, BeyondSpring announced that an abstract, titled, "The Effect of Increasing Doses of Pegfilgrastim on Thrombocytopenia in Breast Cancer Patients Receiving Taxotere, Doxorubicin, Cyclophsophamide and Plinabulin," was accepted for presentation at ESMO (Free ESMO Whitepaper). The abstract evaluated the effects of pegfilgrastim combined with Plinabulin on absolute neutrophil and platelet counts compared to pegfilgrastim alone. The data showed that the combination appears to have a superior product profile over pegfilgrastim in CIN control, platelet counts and bone pain.

In October 2019, BeyondSpring announced the enrollment of the first patient in its Study 106, a global Phase 3 trial with Plinabulin in combination with G-CSF to prevent CIN. The study is the key platform to confirm this finding and bring improved care to patients.

Most recently at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) annual meeting, BeyondSpring presented two e-publications on Study 105 and a poster on Study 106, highlighting Plinabulin’s mechanism of action in preventing CIN.

The Study 105 e-publications titled, "Clinical Evidence of Granulocyte-Monocyte Progenitor (GMP) Stem Cell Involvement in Plinabulin’s Mechanism of Action (MoA) for the Prevention of Docetaxel (Doc) Chemotherapy (Chemo)-Induced Neutropenia (CIN)," and "Clinical Evidence Against the Continuum of Low-Primed Uncommitted Hematopoietic and Progenitor Cells (CLOUD-HSPC) Concept for Hematopoiesis," highlight Plinabulin’s ability to protect hematopoietic stem cells, which differentiates into neutrophils and other white blood cells.

The Study 106 poster titled, "A Randomized Phase 3 Clinical Trial of the Combination of Plinabulin (Plin) + Pegfilgrastim (Peg) versus (vs) Peg Alone for TAC (docetaxel, doxorubicin, cyclophosphamide) Induced Neutropenia (CIN)," provides rationale for the addition of Plinabulin to pegfilgrastim (Neulasta) due to their differing mechanisms of action (MoA) for the prevention against CIN.

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Plinabulin’s Anti-cancer Immune Mechanism and CIN Prevention Mechanism Published in Peer-Reviewed Journals

In October 2019, prestigious Cell publications, Chem and Cell Reports, published novel findings focusing on the mechanism of Plinabulin to mature dendritic cells, which leads to T-cell activation.

The Chem article, titled, "Structure, Thermodynamics and Kinetics of Plinabulin Binding to Two Tubulin Isotypes," outlined research utilizing X-ray crystallography and thermodynamic calculations to demonstrate Plinabulin as a new chemical entity with differentiated binding and kinetics compared to other tubulin binding agents, which gives rise to its differentiated superior efficacy and safety profile in the clinic.

In Cell Reports, titled, "GEF-H1 Signaling Upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses," authors cited Plinabulin’s ability to destabilize microtubule and release the immune defense protein GEF-H1, which is a critical signaling protein for dendritic cell maturation. This leads to the priming of CD8 T-cells. GEF-H1 high immune signature showed better survival in cancer patients, which validated GEF-H1 as a first in class target.

In early December, Cancer Chemotherapy & Pharmacology published an article that examines the mechanism-of-action of Plinabulin and its anti-CIN benefits. The article, titled, "Plinabulin Ameliorates Neutropenia Induced by Multiple Chemotherapies Through a Mechanism Distinct from G‑CSF Therapies," reports the results of an animal study that support the clinical testing of Plinabulin as a non-G-CSF-based treatment for CIN associated with chemotherapies of different mechanisms. Results also support hematopoietic stem/progenitor cells as a focal point for future mechanism-of-action work aimed at understanding the ability of Plinabulin to reduce the serious side effect of cytotoxic therapy in cancer patients.

Strong Intellectual Property Protection through 2036 Globally

In October 2019, BeyondSpring announced that the U.S. Patent and Trademark Office granted the Company a new patent for methods of treating brain tumors by administering Plinabulin. This underscores the Company’s belief that Plinabulin is a first-in-class clinical pipeline asset. Currently, surgery and radiation are the only approved treatments for brain tumors. Chemotherapy has never been approved to treat metastatic brain tumors.

We now have 75 granted Plinabulin patents in 36 jurisdictions and 17 patents granted in the U.S., including the composition of matter patent, with protection to 2036.

Equity Financing

On October 25, 2019, BeyondSpring priced an underwritten public offering of its ordinary shares. The offering was led by Decheng Capital, with gross proceeds of $25.8 million including the overallotment options, before deducting underwriting discounts, commissions and other offering expenses. The Company expects to use the net proceeds to continue clinical and pre-clinical development in addition to general corporate purposes.

Financial Results for the Three Months Ended September 30, 2019

Research and development ("R&D") expenses were $7.2 million for the quarter ended September 30, 2019, compared to $14.1 million for the quarter ended September 30, 2018. The $6.9 million decrease was largely attributable to a $3.9 million decrease in expenses incurred by clinical research organizations and other service fees related to clinical trials, a $0.5 million decrease in preclinical trial expenses and a $0.5 million decrease in non-cash share-based compensation.

General and administrative ("G&A") expenses were $2.5 million for the quarter ended September 30, 2019, compared to $1.5 million for the quarter ended September 30, 2018. The $1.0 million increase was mainly due to the $0.7 million of market research expenses incurred during the quarter ended September 30, 2019.

Net loss attributable to the Company was $9.4 million for the quarter ended September 30, 2019, compared to $14.9 million for the quarter ended September 30, 2018.

As of September 30, 2019, the Company had a cash balance of $24.7 million. With the additional $25.8 million gross proceeds from the recent public offering described above, the Company believes it has sufficient cash to support its clinical trials and submit NDAs in the U.S. and China for Plinabulin for the treatment of NSCLC and CIN, as well as to advance its immuno-oncology pipeline and its ubiquitination protein degradation research platform.

Anticipated Milestones

The following outlines the Company’s anticipated upcoming milestones and projected timelines:

NDA submission to China’s National Medical Products Administration (NMPA) for Plinabulin for CIN – Q1 2020

Final data readout for Study 105 Phase 3 for CIN – H1 2020

Final data readout for Study 106 Phase 3 for CIN – H1 2020

Final data readout for Study 103 Phase 3 for NSCLC – H2 2020

NDA submission to China’s NMPA for Plinabulin for NSCLC – H2 2020

NDA submission to the U.S. Food and Drug Administration (FDA) for Plinabulin for CIN – H2 2020

NDA submission to the U.S. FDA for Plinabulin for NSCLC – H1 2021

Conference Call and Webcast Information

BeyondSpring’s management will host a conference call and webcast today at 8 a.m. Eastern Time to discuss the financial results and provide a corporate update. The dial-in numbers for the conference call are 1-877-451-6152 (U.S.) or 1-201-389-0879 (international). Please reference conference ID 13697474. A live webcast will be available on BeyondSpring’s website at www.beyondspringpharma.com under "Events & Presentations" in the Investors section. An archived replay of the webcast will be available for 30 days.

On December 18, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (Nasdaq:SGEN) reported that the U.S. Food and Drug Administration (FDA) granted accelerated approval to PADCEV for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting (Press release, Astellas, DEC 18, 2019, View Source [SID1234552460]). PADCEV is approved under the FDA’s Accelerated Approval Program based on tumor response rate. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. PADCEV is the first FDA approved treatment in the U.S. for these patients. It is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.1,3

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"Metastatic urothelial cancer is an aggressive and devastating disease with limited treatment options, and the approval of PADCEV is a significant advance for these patients who previously had limited options after initial therapies failed," said Jonathan E. Rosenberg, M.D., Medical Oncologist, Chief, Genitourinary Medical Oncology Service, Memorial Sloan Kettering Cancer Center in New York. "The PADCEV clinical trial enrolled a range of patients whose cancer was difficult to treat, including those whose disease had spread to the liver."

"The FDA approval of PADCEV is welcome news for patients with bladder cancer," said Andrea Maddox-Smith, Chief Executive Officer, Bladder Cancer Advocacy Network. "Though new medicines for bladder cancer have been approved in recent years, most people living with advanced stages of this disease face a difficult journey with few treatment options."

"This approval underscores our commitment to develop novel medicines that address unmet patient needs, and we’re grateful to the patients and physicians whose participation led to this outcome," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas.

"PADCEV is the first antibody-drug conjugate approved for patients facing this aggressive disease, and it is the culmination of years of innovative work on this technology," said Roger Dansey, M.D., Chief Medical Officer, Seattle Genetics.

PADCEV was evaluated in the pivotal trial EV-201, a single-arm phase 2 multi-center trial that enrolled 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy.1 In the study, the primary endpoint of confirmed objective response rate (ORR) was 44 percent per blinded independent central review (55/125; 95% Confidence Interval [CI]: 35.1, 53.2). Among patients treated with the single agent PADCEV, 12 percent (15/125) experienced a complete response, meaning no cancer could be detected at the time of assessment, and 32 percent (40/125) experienced a partial response, meaning a decrease in tumor size or extent of cancer in the body. The median duration of response (DoR), a secondary endpoint, was 7.6 months (95% CI: 6.3, not estimable [NE]). The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). The most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

The FDA’s Accelerated Approval Program allows approval of a medicine based on a surrogate endpoint if the medicine fills an unmet medical need for a serious condition. A global, randomized phase 3 confirmatory clinical trial (EV-301) is underway and is also intended to support global registrations.

On December 18, 2019 Diagnostics firm Shuwen reported it entered into collaboration with ASK Pharma to develop a companion diagnostics (CDx) for novel targets in the oncology space (Press release, Shuwen Biotech, DEC 18, 2019, View Source [SID1234552455]).

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The diagnostics will support ASK’s various novel clinical candidates, which aims to introduce highly innovative and efficacious drugs to the domestic Chinese and international markets. The collaboration will leverage Shuwen’s mature immunohistochemistry (IHC) companion diagnostic platform and is expected to produce a number of market novel diagnostic solutions to hospitals and healthcare providers in the coming years. The collaboration also includes the use of Shuwen’s CAP-accredited central lab to test patient samples from ASK’s clinical trials from clinical sites across China.

On December 17, 2019 Innovative Cellular Therapeutics (ICT), a clinical stage biotechnology company developing a comprehensive platform of chimeric antigen receptor (CAR) T cell therapies for liquid and solid tumors, reported that it has closed a U.S. dollar Series B+ equity financing for an undisclosed amount (Press release, Innovative Cellular Therapeutics, DEC 17, 2019, View Source [SID1234553316]). The lead investor, LH Ventures, is a prominent venture capital firm targeting disruptive technologies in the healthcare sector and other innovations. Proceeds from the capital raise will be used to advance ICTCAR014 – ICT’s next generation CD19-targeting armored CAR-T cell therapy that expresses a dominant negative PD-1 protein to block immunosuppression by cancer cells – into a U.S. clinical trial in the first part of 2020, and to further develop ICT’s "CoupledCAR" CAR-T cell therapy platform in solid tumors.

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"We are deeply impressed by the ICT team, their innovation capabilities and the response of the initial patients to the Company’s next generation armored dominant negative PD-1 CAR-T cell therapy and CoupledCAR technologies," said Xin Xie, Ph.D., Partner at LH Ventures. "We believe ICT’s platform technologies will create significant breakthroughs in the fight against both liquid and solid tumors."

"We are excited to have LH Ventures support the expansion of our global activities and help us advance the clinical development of our next generation CAR-T technologies for liquid and solid tumors in the United States," said Larry (Lei) Xiao, Ph.D., ICT’s Founder and Chief Executive Officer. "They are joined by a group of other renowned, international investors who also believe in the viability of our platform technologies."

About LH Ventures
LH Ventures is a prominent venture capital firm targeting early stage opportunities of innovation and disruptive technologies. It boasts an investment team consisting of entrepreneurs, scientists, doctors, and capital market experts. LH Ventures identifies teams and companies which have significant value potential and helps them grow into industry leaders.

About ICTCAR014
The U.S. Food and Drug Administration (FDA) has cleared ICT’s Investigational New Drug (IND) application for ICTCAR014, a next generation CD19-targeting CAR-T cell therapy that expresses a dominant negative PD-1 protein to block immunosuppression by cancer cells. ICT is moving ICTCAR014 into a U.S. clinical trial. ICTCAR014, referred to as an "armored" CAR-T cell therapy, has already shown encouraging results in proof-of-concept human trials in China. As highlighted in ICT’s presentation at the November 2019 Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting, ICTCAR014 demonstrated a 92.3% objective response rate (53.8% complete remission; 38.5% partial remission) in 13 initial patients with relapsed or refractory non-Hodgkin lymphoma. Significant tumor shrinkage and limited toxicity were observed.

On December 17, 2019, Sangamo Therapeutics, Inc. (the "Company") reported that it has entered into a letter amendment (the "Letter Amendment") to its Collaboration and License Agreement with Pfizer, Inc. ("Pfizer"), dated May 10, 2017 (the "Collaboration Agreement"), to accelerate the transfer of the Investigational New Drug application ("IND") for the Company’s SB-525 product candidate to Pfizer (the "IND Transfer") (Filing, 8-K, Sangamo Therapeutics, DEC 17, 2019, View Source [SID1234552572]). The Letter Amendment obligates the Company to cooperate and assist Pfizer with certain activities related to the IND Transfer and as of December 18, 2019, the IND had been transferred to Pfizer. In addition, the Letter Amendment changes the timing of Pfizer’s payment to the Company of a $25.0 million development milestone, and as of December 20, 2019, the Company met the conditions for earning such milestone. No other changes were made to the provisions of the Collaboration Agreement governing milestones or royalties as part of the Letter Amendment. Under the Collaboration Agreement, the Company is eligible to receive development milestone payments contingent on the achievement of specified clinical development, intellectual property, regulatory and first commercial sale milestones for SB-525 and potentially for other products, and is also eligible to receive tiered royalties with percentages starting in the low teens and up to 20% based on the annual net sales of each potential licensed product developed under the Collaboration Agreement, subject to reduction due to patent expiration, entry of biosimilar products to the market and payment made under certain licenses for third-party intellectual property.

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The foregoing is only a brief description of the Letter Amendment, does not purport to be complete and is subject to, and qualified in its entirety by, the full text of the Letter Amendment. The Company intends to file a copy of the Letter Amendment with its Annual Report on Form 10-K for the year ending December 31, 2019.