Lan Huang
Thank you, Garth, and thank you, everyone, for joining our call today. On the call with me today are Dr. Ramon Mohanlal, our Chief Medical Officer; and Richard Brand, our Chief Financial Officer. I'm delighted to welcome everyone to our first investor communications being successfully completing our initial public offering on March 9. As this is our first quarterly conference call, I want to take this opportunity to provide a broad overview of BeyondSpring.
BeyondSpring is a late-stage global clinical development company with a robust immuno-oncology pipeline. Our lead asset, plinabulin, is currently in global registrational trials for 2 large cancer indications with near-term catalysts over the next 6 to 12 months. We also have several preclinical IO drug candidates and a research platform targeting ubiquitination degradation pathway in collaboration with University of Washington. BeyondSpring is committed to developing drugs in a manner that benefits both the patient and the medical community. We are confident that our disrupted U.S.-China drug development model has the potential to result in a more efficient and cost-effective drug trial process, which in turn should reduce time to market and may ultimately reduce cost to the patient, solving the pricing problem of innovative medicine. Finally, I'm gratified to have been able to assemble a world-class internal team who collectively have brought to market more than 30 innovative drugs. And I am appreciative of the support we have received from the Fred Hutchinson Cancer Research Center and the University of Washington through our significant collaboration.
Our lead asset, plinabulin, is a synthetic analog of a marine-derived small molecule, which alters the tumor microenvironment and may provide multiple therapeutic opportunity. Through our 3-year collaborative effort with the University of Basel and Massachusetts General Hospital, now we understand that plinabulin is a GEF-H1 activator. Plinabulin destabilizes microtubule network in the cell's cytoskeleton and releases the guanine nucleotide exchange factor, GEF-H1. This activates downstream signal transduction pathways, leading to dendritic cell, DC, maturation, T-cell activation and neutropenia prevention. Plinabulin is differentiated from other microtubule depolymerization agents such as the CA4P class, which cannot induce DC maturation or neutropenia prevention.
BeyondSpring acquired the rights to plinabulin from San Diego-based Nereus Pharmaceuticals for the Hong Kong and China rights in 2010 and expanded our reach by acquiring the global rights in 2013 in exchange for 10% of our pre-IPO shares and no royalty payment. Nereus conducted the Phase I/II trial with Quintiles as the CRO in the U.S. and other Western countries. This is the data from which is the basis of our current Phase III trial. BeyondSpring is grounded on a novel, highly scalable business model for drug development that aims to leverage integrated clinical resources in the United States and China to develop innovative cancer therapy. We are confident that conducting trials in China provides BeyondSpring with a competitive advantage, including accelerated clinical enrollment, reduced trial costs and faster regulatory approval process, and very importantly, access to the country's large and growing cancer patient population. No different than other industries, drug development has become a global process. In fact, more than half of our clinical trial sites today are held outside of the U.S., which means that 80% of applications to the U.S. FDA for drugs and biologics include data from ex-U.S. clinical sites. This also includes China, which has developed a world-class clinical drug trial infrastructure, adhering to the most stringent and U.S. FDA-accepted clinical and regulatory standards.
BeyondSpring is not alone in integrating China into its clinical trials process and data submissions to the U.S. FDA. Examples of these efforts include afatinib, a first-line non-small cell lung cancer drug that was approved by the U.S. FDA in July 2013, which had 72% of patient data from China in Stage 3 trials. Another example is AstraZeneca's IRESSA, which received EMA approval for first-line non-small cell lung cancer, with 99% of pivotal trial data coming from China. China also had participated in Phase III trials for the approval of AstraZeneca's Tagrisso, Bayer's NEXAVAR and Pfizer's crizotinib. To support our robust pipeline, innovative business model and objective, BeyondSpring has assembled very tremendously talented senior leadership team, which is comprised of individuals, each at the top of their game, with decades of experience in drug development. I'm a scientist turned entrepreneur with over a decade experience in the U.S. and China. I was trained at UC Berkeley and Memorial Sloan Kettering Cancer Center. And BeyondSpring is my fourth company. In 2009, I was very honored to be the recipient of China's Thousand Talent Innovator Award, an important distinction in China. Dr. Ramon Mohanlal, our Chief Medical Officer, has over 20 years of global experience in strategic drug development at big pharma and biotech start-up. He has played a crucial role in bringing 5 drugs to the market. Shortly before joining us, Dr. Mohanlal was the clinical head of established oncology products for Novartis.
Dr. Ken Lloyd, our Chief Scientific Officer, has more than 45 years of experience in the pharmaceutical industry, with a focus on novel drug discovery and development, working in large pharmas such as Hoffman LaRoche and Wyeth. He was integral in bringing 6 drugs to the market, including Ambien. And finally, Dr. Gordon Schooley, our Chief Regulatory Officer, has 35 years of experience in the pharmaceutical industry, with a focus on clinical and regulatory affairs. Dr. Schooley has been associated with product development and approvals of 19 marketed drugs in the U.S., EU and Pacific Rim countries.
Switching gears, allow me to provide greater detail surrounding our work in the clinic. For today's discussion, I'm going to center my discussion around BeyondSpring's most advanced drug indication. Although it is worth expressing the excitement, we have a number of our preclinical trial candidates, which activate T-cell and are producing new antigens, turning cold tumor into hot. Plinabulin is our lead asset. In combination with docetaxel, a leading chemotherapy, has delivered encouraging data in the Phase II portion of the Phase I/II clinical trial in the U.S. and other Western countries in the reduction of docetaxel-induced severe neutropenia and as an anticancer agent in increasing overall survival in a subset of patients with advanced non-small cell lung cancer who have measurable lung lesion. As a consequence of this clinical result, our current efforts are focused on 3 indications: number one, chemotherapy-induced severe neutropenia across several types of cancer; number two, in combination with docetaxel for advanced non-small cell lung cancer; and number three, in combination with nivolumab for advanced non-small cell lung cancer. We believe that pursuing this prospect provides BeyondSpring with the opportunity to seek regulatory approval for plinabulin for multiple indications.
For the first indication of prevention of chemotherapy-induced neutropenia, let me share with you its background and market potential. Neutropenia is an abnormally low concentration of neutrophils. Neutrophil is a type of white blood cell, which may result from an abnormal rate of destruction or low rate of synthesis of white blood cells in the bone marrow. Specifically, patients with low neutrophil counts are more prone to bacterial infection, which are a significant cause of mortality in cancer patients. Every year, more than 60,000 patients in the U.S. are hospitalized for neutropenia associated with fever and infection, resulting in a mortality rate of between 9% and 18%.
The current standard of care for neutropenia is biologic drugs based on G-CSF, a human growth factor that stimulates the level of white blood cells, also known as neutrophils. While annual worldwide sales of G-CSF drugs such as Amgen's Neulasta exceed $7.3 billion, they are limited by safety concerns and are required to be administered the day after chemotherapy use, which represents a significant inconvenience and a potential danger to patients. In contrast, plinabulin is administered on the same day 1 hour after chemo, which we believe is a more effective and tolerable cost of treatment.
Data from the Phase II study was extremely encouraging, where plinabulin reduced severe neutropenia induced by docetaxel from 26% to less than 5% with a p-value of 0.0003, with 3 0s in the middle. So this is highly statistically significant. This data was generated in around 20 patients, which underscores plinabulin's material effect. This data was later presented at December 2016 ASH meeting. Now based on the clinical profile of plinabulin and our communication with FDA, we are starting enrolling patients in 2 Phase II/III trials of plinabulin for the prevention of neutropenia across several types of cancer.
The first trial is a Phase II/III trial in around 200 patients in the United States, other Western countries and China of plinabulin in combination with docetaxel in patients with solid tumor consists of breast cancer, prostate cancer and non-small cell lung cancer. The primary endpoint for this trial is noninferiority in duration of severe neutropenia in the first cycle compared to pegfilgrastim or Neulasta. Each cycle is only 21 days, so the trial is very short. And I'm very excited to report to you all that we have enrolled the first patients in this trial and expect to obtain initial result for the Phase II portion in the second half of 2017 and interim data for the Phase III portion in the first half of 2018.
The second trial will be a Phase II/III trial in around 200 patients in the United States, other Western countries and China of plinabulin in combination with a myelosuppressive chemo regimen consisting of 3 agents, TAC, in patients with breast cancer. The design of this trial will be substantially similar to the ongoing trial of plinabulin with docetaxel. However, this trial will be powered to measure superiority in duration of severe neutropenia in the first cycle. We expect to commence this trial in the first half of 2017 and to obtain final results from this trial in the first half of 2019.
Dr. Douglas Blayney of Stanford, a board member of the National Comprehensive Cancer Network, NCCN, and a contributor to the NCCN Guidelines for neutropenia management, is our principal investigator for both trials. If our Phase II/III plinabulin trials are successful, we intend to submit an NDA for a broad indication for prevention of severe neutropenia induced by all myelosuppressive agents.
Our second indication for plinabulin is in combination with docetaxel for advanced non-small cell lung cancer, which accounts for around 87% of lung cancer cases, and it is where BeyondSpring is directing its efforts. Despite availability of multiple drugs to treat non-small cell lung cancer, we believe there remains a great need for novel therapies in this field.
Data from the Phase II portion of the Phase I/II trial in non-small cell lung cancer suggests that the addition of plinabulin to docetaxel may increase antitumor activity compared to docetaxel alone. Specifically, a subset of 38 patients with measurable lung lesions given a combination of docetaxel plus 30 milligrams per liter square plinabulin had a median survival of 11.3 months compared to 6.7 months in docetaxel alone. In addition, the plinabulin plus docetaxel cohort had an objective response rate, a measure of the proportion of patients with tumor size reduction of at least 30%, of 18.4% compared to 10.5% for the docetaxel monotherapy arm. While the number of patients in the subset was not large enough to demonstrate statistical significance, we and our clinical collaborators believe this data suggest the addition of plinabulin to a standard regimen of docetaxel may provide a clinically meaningful increase in antitumor activity compared to docetaxel alone.
In summary, the result of this randomized trial was given as an oral presentation at the 2017 ASCO-SITC Clinical Immuno-Oncology Symposium by Dr. Alain Mita of Cedars-Sinai Medical Center, Los Angeles.
The Phase III trial is actively enrolling in the U.S., China and Australia. This trial is expected to enroll 550 patients, 80% of whom will be in China and 20% at sites in the United States and Australia. The primary endpoint is overall survival. We'll utilize this data from this trial to submit approval applications in the U.S. and China, which represent the 2 of the largest pharmaceutical markets in the world.
With the fastest-growing cancer market in the world, around 700,000 cases of lung cancer diagnosed in China in 2015, the treatment of lung cancer is a health care priority in China. In addition, as I am a recipient of China's Thousand Talent Innovator Award, BeyondSpring is eligible for an accelerated review track for approval by the CFDA. Our lead clinical investigator in the United States is Dr. Luda (sic) [ Lyudmila ] Bazhenova from University of California, San Diego. Dr. Bazhenova was a principal investigator for the Phase II portion of the Phase I/II trial of plinabulin and has been an investigator of over a dozen lung cancer trials. Our lead clinical investigator in China is Dr. Yan Sun, the Director of National Academy of Science Cancer Hospital in Beijing, a hospital that treats 320,000 patients a year. Dr. Sun was also the lead clinical investigator for the Phase III trials of other lung cancer drugs that received approval from the CFDA. He was trained at MD Anderson and is a National Academy of Science member in China. We anticipate interim data for this trial to be available in the first quarter of 2018 and the final data available in first quarter of 2019. Multiple U.S.-based Phase I/II trials of plinabulin, in combination with nivolumab, have received regulatory approval. In September 2016, the University of California, San Diego, enrolled the first patient in the investigator-sponsored Phase I/II trial. In addition, the Fred Hutchinson Cancer Center and the University of Washington are planning to launch another investigator-initiated Phase I/II trial. We expect to initiate a global pivotal trial of plinabulin in combination with PD-1 in 2018.
The work we are doing with plinabulin and the talented team we have assembled has attracted exciting collaborations for R&D and preclinical and clinical research. We are collaborating with Dr. Ning Zheng, a Howard Hughes Medical Institute Investigator, and his group at the University of Washington on a unique molecular group to selectively target certain oncogene proteins with E3 ligase, which is one of the ubiquitin ligase enzymes. Dr. Zheng and I were the first to solve the crystal structure of 2 classes of E3 ligases and this discovery formed the structural basis in selecting the small molecules to be studied as a potential molecular glue agent.
With the capital we raised through the IPO and the concurrent private placement, we have a clear path forward to the clinical programs I have discussed, as well as some of our earlier-stage clinical trials. We look forward to providing additional updates in the quarters and years to come.
With that, I will turn the call over to Richard.
