On June 21, 2018 BeyondSpring Inc. (the "Company" or "BeyondSpring") (NASDAQ:BYSI), a global, clinical-stage biopharmaceutical company focused on the development of transformative cancer therapies, reported its financial results for the quarter ended March 31, 2018, and provided an update on the Company’s operations (Press release, BeyondSpring Pharmaceuticals, JUN 21, 2018, View Source [SID1234527596]).

"During the past few months, we have continued to execute on our strategy to establish our lead asset, Plinabulin, as a potentially superior new therapy for the treatment of chemotherapy-induced neutropenia, or CIN, while also advancing our Phase 3 non-small cell lung cancer trial and earlier-stage programs," said Lan Huang, Ph.D., Chairman, Chief Executive Officer and Co-Founder of BeyondSpring. "We recently highlighted data from the Plinabulin development program describing its differentiated mechanism of action and positive results from the Phase 2 portion of 105 Study, which together, further articulates the potential of our novel candidate to prevent severe neutropenia with less bone pain and an overall more favorable product profile than G-CSF therapy. We look forward to building on this momentum as we approach key Phase 3 data readouts for CIN and non-small cell lung cancer beginning later this year, advance our early-stage pipeline of immuno-oncology therapies and research activities for our ubiquitination protein degradation research platform, and prepare to initiate Phase 1 trials later this year for multiple triple-combination immuno-oncology programs. We have already started the process of preparing to commercialize in both China and the U.S., including identifying and securing the resources and talent we need to put in place for commercial success for Plinabulin in both markets. With significant upcoming milestones, BeyondSpring is well positioned to transition into a multinational, commercial-stage oncology company."

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Recent Highlights

Data from the Phase 2 portion of Study 105 comparing Plinabulin and Neulasta (pegfilgrastim) for prevention of CIN presented at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting

In June 2018, results of the Phase 2 portion of Study 105, a prospective Phase 2/3 trial of its lead asset, Plinabulin, were presented by BeyondSpring in a poster session at the ASCO (Free ASCO Whitepaper) Annual Meeting. The Phase 2 portion of Study 105 was designed as a head-to-head comparison of different dose levels of Plinabulin to Neulasta in a total of 55 patients. The Phase 2 portion met its primary endpoint, which was to determine the recommended Phase 3 Plinabulin dose. Data from the study demonstrated that patients treated with Plinabulin dosed 30 minutes after docetaxel for the prevention of docetaxel CIN reported less bone pain, which was clinically meaningful, and had superior neutrophil counts and comparable neutropenia reduction compared to patients treated with Neulasta 24 hours after docetaxel. The data suggested that Plinabulin has the potential to be at least as effective as Neulasta for prevention of CIN, with an overall product profile that could address the limitations of the current standard of care.

Plinabulin mechanism data highlighted at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting

In April 2018, BeyondSpring presented preclinical data related to Plinabulin’s differentiated mechanism of action at the AACR (Free AACR Whitepaper) annual meeting. The data demonstrated Plinabulin’s novel mechanism in preserving neutrophils in bone marrow after docetaxel chemotherapy treatment – a mechanism that is differentiated from that of G-CSF, which is the current standard of care in the prevention of CIN.

The Company offered shares through a registered direct offering for gross proceeds of $20.0 million

On May 29, 2018, BeyondSpring entered into private placement agreements with certain third-party investors pursuant to which the Company agreed to issue and sell, in a registered direct offering by the Company, an aggregate of 739,095 shares of the Company’s ordinary shares at a purchase price of $27.06 per share, for aggregate gross proceeds of $20.0 million. These investors, including an insurance company and a pharmacy retail chain owner in China, may be strategic to BeyondSpring’s planned commercial initiatives in China.

Edward Dongheng Liu appointed Chief Financial Officer

In March 2018, the Company announced the appointment of Edward Dongheng Liu as Chief Financial Officer. Mr. Liu was a senior banker at J.P. Morgan and Jefferies in Hong Kong, and was a partner and executive director of Epiphron Capital, a cross-border healthcare fund and Series B investor in BeyondSpring.

Financial Results of Three Months Ended March 31, 2018

Research and development (R&D) expenses were $14.1 million for the quarter ended March 31, 2018, compared to $46.7 million for the quarter ended March 31, 2017. R&D expenses for the first quarter of 2017 included a $42.3 million non-cash charge for acquiring the worldwide patent of Plinabulin excluding the People’s Republic of China (PRC) and Hong Kong, which is determined based on the fair value of issued 2,112,963 ordinary shares at $20 per share. Excluding the impact of this purchase, the R&D expense for the quarter ended March 31, 2018 would have increased by $9.7 million, compared to the quarter ended March 31, 2017. This increase is largely attributable to $4.9 million of non-cash share-based compensation expense recorded in the first quarter of 2018, $2.8 million related to increased clinical trial expense and $1.4 million related to increased professional services expense.

General and administrative ("G&A") expenses were $0.7 million for the quarter ended March 31, 2018, compared to $1.0 million for the quarter ended March 31, 2017. First quarter 2018 G&A expenses included a $0.7 million non-cash credit relating to the forfeiture of certain restricted shares.

U.S. GAAP net loss was $14.1 million for the quarter ended March 31, 2018, compared to $47.7 million for the quarter ended March 31, 2017. Net loss for the first quarter ended March 31, 2017, included a $42.3 million non-cash charge for acquiring the worldwide patent of Plinabulin excluding the PRC and Hong Kong.

Cash and short-term investments were $21.5 million at March 31, 2018, compared to $30.6 million at December 31, 2017. The Company anticipates that its current financial resources, including the proceeds from the private placement, would enable it to advance its ongoing clinical trials and submit New Drug Application (NDA) in China for Plinabulin for the treatment of CIN and non-small cell lung cancer in late 2018 or early 2019 and in the first half of 2019, respectively, and to advance its immuno-oncology pipeline, as well as its ubiquitination protein degradation research platform.

Key Upcoming Milestones

The following outlines the Company’s key anticipated upcoming milestones for the next 12 months.

Announce Phase 3 interim analysis data for Study 105 evaluating Plinabulin + docetaxel for CIN – 4Q 2018

Announce topline Phase 2 data for Study 106 evaluating Plinabulin + TAC (Taxotere/Adriamycin/cyclophosphamide) for CIN – late 2018

Announce Phase 3 interim data for Study 103 evaluating Plinabulin + docetaxel for non-small cell lung cancer (NSCLC) – early 2019

Submit NDA to China Food and Drug Administration (CFDA) for Plinabulin for CIN – late 2018/early 2019

Advance two Plinabulin triple-combination immuno-oncology programs into Phase 1 – 2H 2018

Submit NDA to CFDA for Plinabulin for NSCLC – 1H 2019

Advance ubiquitination protein degradation research platform, BPI-001, first target of mutant KRAS, lead asset – 2019

Advance new pipeline asset, BPI-002, an oral CTLA-4 inhibitor, into Phase 1 – 2019

About Plinabulin
Plinabulin, a marine-derived small-molecule, is BeyondSpring’s lead asset and is currently in late-stage clinical development for the prevention of CIN and as an anticancer therapy in NSCLC. Studies of Plinabulin’s mechanism of action indicate that Plinabulin activates GEF-H1, a guanine nucleotide exchange factor. GEF-H1 activates downstream transduction pathways leading to the activation of the protein c-Jun. Activated c-Jun enters the nucleus of dendritic cells to up-regulate immune-related genes, which contributes to the up-regulation of a series of genes leading to dendritic cell maturation, T-cell activation and other effects that prevent neutropenia by reducing the neutrophil breakdown.

On June 21, 2018 PharmaEngine Inc. (TWO: 4162) and its corporate partner, Nanobiotix S.A. (Euronext: NANO) reported that PEP503 (NBTXR3) in combination with radiotherapy met the primary endpoint of pathological Complete Response Rate (pCRR) as compared to radiotherapy alone in a global pivotal phase II/III trial in patients with locally advanced soft tissue sarcoma (STS) of the extremity and trunk wall (Press release, PharmaEngine, JUN 21, 2018, View Source [SID1234527423]). The pCRR on the combination arm was 16.1% as compared to 7.9% for the control arm of radiotherapy alone (p = 0.0448). Also PEP503 activated by radiation demonstrated a significant increase of R0 resection rate as compared to radiation alone (p = 0.042). PEP503 demonstrated a good local tolerance among this patient population. The findings showed a very similar radiation-related safety profile in both arms.

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This prospectively randomized, multi-national, open-label and active controlled two-arm (1:1 ratio) pivotal phase II/III trial, referred to as Study 301 (act.in.sarc study) has been conducted in partnership with Nanobiotix. PharmaEngine is the co-sponsor of this study in Asia-Pacific Region. The antitumor activity and safety of PEP503 combined with radiotherapy in Study 301 was compared with that of radiotherapy alone, as preoperative treatment. The primary objective of Study 301 is to enhance pCRR by dosing PEP503 through intra-tumor injection and then activated by standard dose (25 x 2 Gy) of external beam radiation therapy (EBRT). The secondary endpoints are the objective response rate (ORR) by imaging (MRI); the tumor volume changes; the resection margins (R0 rate) and the limb amputation rate, as well as the evaluation of the safety profile in term of clinical and laboratory adverse events. The detailed data analysis, with the exception of long-term follow up will be reported in an international medical conference in the next few months.

"We are very pleased to take part in the global study alongside with Nanobiotix, and are excited that PEP503 has achieved the primary and secondary endpoints of this pivotal study in STS patients," said C. Grace Yeh, Ph.D., President and Chief Executive Officer of PharmaEngine. "The promising results from this study validated its fundamental mechanism of action as a radio-enhancer, which is expected to be generally applicable in other cancers treated with radiotherapy. In addition, previously reported preliminary data from a small set of tumor samples in this study demonstrated that PEP503 activated by radiotherapy induces a specific adaptive immune pattern as an immune-enhancer, while radiotherapy alone did not show any impact on triggering adaptive immune response."

About Study 301 (act.in.sarc study)

The Study 301 recruited a total of 180 patients in Europe (36 sites in 10 countries) by Nanobiotix, and in Asia-Pacific region (7 sites in Australia, Hong Kong, and Philippines) by PharmaEngine. The Global Principal Investigator is Dr. Sylvie Bonvalot, MD, PhD (Head of Sarcoma and Complex Tumor Surgery Unit, Institut Curie, Paris, France). The primary endpoint of pCRR is defined as the rate of patients showing less than 5% of residual viable cancer cells in the tumor post treatment. A centralized evaluation of the pathological response was performed. For additional information, please visit www.clinicaltrials.gov. (Identifier: NCT02379845).

About PEP503 (NBTXR3)

PEP503, the lead project of the NanoXray pipeline of Nanobiotix, is a nanoparticle formulation of hafnium oxide crystals. It is a first-in-class product designed to destroy, when activated by radiotherapy, tumors through physical cell death and metastasis via immunogenic cell death leading to specific activation of the immune system. In August 2012, PharmaEngine licensed the development and commercialization rights of NBTXR3 in the Asia-Pacific region from Nanobiotix. In addition to STS, Nanobiotix and PharmaEngine are performing clinical trials in head & neck cancers, liver cancers (liver metastasis and hepatocellular carcinoma), rectal cancer, prostate cancer, as well as in combination with anti-PD1 antibodies in head & neck cancers and non-small cell lung cancer. PEP503 has been classified as a class III medical device in many European and certain Asian countries.

About Soft Tissue Sarcoma (STS)

STS are rare malignant tumors that arise from extraskeletal connective tissues, accounting for 0.7% of all cancers. They can occur anywhere in the body, but most originate in an extremity and the trunk (78%). The conventional treatment for STS is wide margin surgery whenever possible with the addition of radiotherapy. In locally advanced STS, however, clear margins are not often achievable, which could lead to higher local failure rates, and negatively affect overall survival. Scientific reports have demonstrated how preoperative radiotherapy can offset the negative prognostic impact of marginal resection on local outcome and survival for patients with STS, extending the limit of limb and function preservation.

Although improvements in surgical techniques and preoperative radiotherapy have been made, local tumor recurrence and distant metastases have been frequently noted to develop. PEP503 (NBTXR3), a radio-enhancer designed to maximize x-ray absorption within the tumor, aims to improve the efficacy of radiotherapy and increase the feasibility of surgical tumor removal.

On June 21, 2018 Xspray Pharma reported the company has obtained approval from the Swedish Medical Products Agency (MPA) to carry out a previously announced clinical study of the formulation of the company’s product candidate HyNap-Dasa (Press release, Xspray, JUN 21, 2018, View Source [SID1234650102]). The study is part of Xspray’s clinical program and will be completed during the third quarter. The objective is to confirm the bioequivalence of the optimized formulation developed by Xspray, based on the company’s patented RightSize-technology.
"We are pleased with the progress of the project and following the decision of the MPA, we can now proceed with our plan for clinical studies," commented Per Andersson, CEO of Xspray Pharma.

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The current study is intended to confirm the formulation of the product candidate HyNap-Dasa. The results will form the basis of the following registration studies. The results from the current study are expected to be available by the end of the third quarter.

HyNap-Dasa is the first in a portfolio of product candidates that Xspray Pharma is developing with the target to haver products ready to launch on the US market during 2020-2026. All of the product candidates in the portfolio are versions of cancer drugs currently on the market, based on protein kinase inhibitors (PKI) and used for cancer treatments.

On June 20, 2018 Aminex Therapeutics, Inc., a clinical-stage drug development company focused on advancing a novel cancer immunotherapy, reported it received clearance from the Food and Drug Administration to initiate the first Phase 1 clinical trial of its immuno-oncology drug candidate AMXT 1501, a small molecule polyamine uptake inhibitor, and the approved drug DiFluoroMethylOrnithine (DFMO, eflornithine), a polyamine synthesis inhibitor (Press release, Aminex Therapeutics, JUN 20, 2018, View Source [SID1234527410]). This immunotherapy treatment will be evaluated in patients with a broad range of advanced solid tumor cancers.

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The open label, multicenter, dose-escalation trial will evaluate the safety and tolerability of AMXT 1501 alone, and in combination with DFMO, in more than 50 patients with advanced solid tumors. The trial will include a dose-ranging stage followed by an expansion phase. Evaluation of pharmacokinetics, pharmacodynamics and clinical response rates will be assessed. The trial is listed on the NIH clinical trial registry www.clinicaltrials.gov (Identifier: NCT03536728). NEXT Oncology of San Antonio, Texas is the first of four clinical sites planned for this trial. The first cancer patient received an initial dose on June 12, 2018.

"Initiating this first trial of our unique immunotherapy approach represents a significant milestone for Aminex Therapeutics. We are extremely excited to begin clinical evaluation of this investigational therapy that has demonstrated significant promise in many preclinical studies involving multiple animal solid tumor cancer models," said Jim Skaggs, Chief Executive Officer and Chairman of the Board of Aminex Therapeutics. "The primary goal of this trial is to determine the safety and appropriate dosage of AMXT 1501 and DFMO in combination. Efficacy indications will also be assessed. We are also pleased to announce the closure of a $10 million series B financing to support our clinical development efforts."

Aminex Therapeutics’ immunotherapy approach combines the company’s oral, small molecule polyamine uptake inhibitor, AMXT 1501, with the off-patent polyamine synthesis inhibitor, DFMO, approved for African sleeping sickness. AMXT 1501 is designed to work in conjunction with DFMO to constrain the production and uptake of polyamines – molecules found in high concentrations in cancer cells and linked to immune system suppression. Reducing polyamines and, in turn, decreasing myeloid-derived suppressor cells in the tumor microenvironment, allows for activation of the immune system to attack solid tumors. In preclinical studies involving multiple cancer models, AMXT 1501 + DFMO has been shown to be especially effective against cancers driven by MYC and RAS, two major oncogenes known to promote the development of many types of solid tumor cancers.

Aminex Therapeutics, which is led by an experienced management team, board of directors and scientific advisory board, announced the strengthening of its leadership team with the earlier appointments of Roger Ulrich, Ph.D. to its Board of Directors and Stephen B. Baylin, M.D., as member of the Scientific Advisory Board and clinical advisor. Dr. Ulrich is a founder of Calistoga Pharmaceuticals and formerly with Acerta Pharma, Merck, Abbott Laboratories and The Upjohn Company. He currently serves as director for Acerta Pharma, Remedy Pharmaceuticals and is a Senior Advisor to Frazier Healthcare Partners. Dr. Baylin is Virginia and D.K. Ludwig Professor of Oncology and Medicine, Co-Director of the Cancer Biology Division and Associate Director for Research Programs of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

On June 20, 2018 SillaJen, Inc., (KOSDAQ:215600), a clinical-stage, biotherapeutics company focused on the development of oncolytic immunotherapy products for cancer, reported the first patient has been enrolled in REN026, the Phase 1b clinical trial of Pexa-Vec (pexastimogene devacirepvec) in combination with cemiplimab (REGN2810) for the treatment of renal cell cancer (RCC) (Press release, SillaJen, JUN 20, 2018, View Source [SID1234527430]). The first patient was enrolled in the United States, with expansion to sites in South Korea and Australia anticipated over the coming weeks.

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SillaJen is collaborating with Regeneron to evaluate Pexa-Vec, SillaJen’s lead clinical candidate, in combination with Regeneron’s cemiplimab, an anti-PD1 monoclonal antibody. The aim of the trial is to assess the safety and efficacy of the combination in patients with unresectable or metastatic renal cell carcinoma. The study will also investigate the immune modulating potential of Pexa-Vec given concurrently with checkpoint inhibitor therapy by evaluating multiple blood and tissue biomarkers.

"Given the initial activity seen with Pexa-Vec monotherapy and the potential of oncolytic viruses to enhance anti-tumor immunity, combining Pexa-Vec with cemiplimab is quite rational and has the promise to build upon the activity of checkpoint inhibitor therapy alone in RCC. This trial will not only assess the clinical activity of the two agents but allow us to assess in more depth the changes elicited in anti-tumor immunity following treatment by examining peripheral blood and tumor samples. This will give us proof of concept data that will help us expand this approach to other tumor types," stated James Burke, M.D., chief medical officer at SillaJen.

About Pexa-Vec and the SOLVE Platform
Pexa-Vec is the most advanced product candidate from SillaJen’s proprietary SOLVE (Selective Oncolytic Vaccinia Engineering) platform. The vaccinia strain backbone of Pexa-Vec has been used safely in millions of people as part of a worldwide vaccination program, and over 300 cancer patients have been treated with Pexa-Vec to date. Pexa-Vec was engineered to target common genetic defects in cancer cells by deleting their thymidine kinase (TK) gene, thus making Pexa-Vec dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF) protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack. Pexa-Vec has been shown to be effective when delivered both intratumorally and systemically by intravenous administration. Pexastimogene devacirepvec (Pexa-Vec) is currently being evaluated in a worldwide Phase 3 clinical trial for advanced primary liver cancer, and more information can be found at: View Source