BeyondSpring(US:BYSI)2021-04-29 16:00Financing and IPO - BeyondSpring Inc. completed its initial public offering in March 2017, raising gross proceeds of $54.3 million from selling 174,286 ordinary shares [335]. - In November 2020, the company raised $86.3 million from an underwritten offering, selling 8,625,000 ordinary shares [339]. - The company is exploring strategic financing options, including equity offerings and potential licensing arrangements, to support operations and future growth [361]. - SEED, a subsidiary, entered a collaboration with Lilly, receiving a $15 million upfront payment and potential milestones of up to $780 million [340]. - SEED, a subsidiary focused on targeted protein degradation, received a $15 million upfront cash payment from Lilly and is eligible for up to $780 million in potential milestones [508]. Product Development and Clinical Trials - Plinabulin, the company's lead asset, is at NDA-stage for preventing chemotherapy-induced neutropenia (CIN) and has received Breakthrough Therapy Designation from both the FDA and NMPA [341]. - The PROTECTIVE-2 Phase 3 study demonstrated a statistically significant improvement in the rate of prevention of grade 4 neutropenia, improving from 13.6% to 31.5% (p=0.0015) [346]. - The DUBLIN-3 Phase 3 trial has completed global enrollment of 559 patients, focusing on Plinabulin's efficacy in combination with docetaxel for advanced NSCLC [345]. - The company has developed three small molecule immune agents currently in preclinical stages, expanding its pipeline of innovative therapies [341]. - The company has completed two Phase 2/3 trials for CIN and submitted NDAs in both the U.S. and China, with ongoing global clinical trials for Plinabulin [397]. Market Potential and Growth - The U.S. CIN market is approximately $4 billion and is expected to grow significantly, with over 70% of chemotherapy patients qualifying for prophylaxis under updated NCCN guidelines [343]. - The global NSCLC market is projected to grow at a rate of 11.7% per year, with estimated sales of $24.7 billion in 2020 and $48.1 billion by 2026 [462]. - The current U.S. CIN market is approximately $4 billion and is expected to grow significantly due to updated NCCN guidelines, which now include over 70% of chemotherapy patients qualifying for CIN prophylaxis [363]. - Plinabulin aims to address the "Neutropenia Vulnerability Gap" by providing protection in the first week after chemotherapy, where over 75% of CIN-related complications occur [414]. Efficacy and Safety of Plinabulin - Plinabulin has shown a 20% reduction in grade 4 Treatment Emergent Adverse Events (TEAE) compared to pegfilgrastim, indicating a better safety profile [346]. - The combination of Plinabulin and pegfilgrastim met all primary and key secondary endpoints in the PROTECTIVE-2 study, including a reduction in the duration of severe neutropenia and clinical complications [366]. - Plinabulin demonstrated a statistically significant reduction in the incidence of grade 3 and 4 neutropenia adverse events from 26% in the docetaxel monotherapy arm to 7% in the Plinabulin plus docetaxel arm in the Phase 2 portion of Study 101 [367]. - The hospitalization rate for patients with profound neutropenia was 8.3% in the Plinabulin and pegfilgrastim combination arm, compared to 11.8% in the pegfilgrastim arm [356]. - Patients treated with Plinabulin experienced no cases of sepsis or severe infections, while 3.6% of patients in the docetaxel monotherapy arm did [422]. Mechanism of Action - Plinabulin's mechanism of action differs from G-CSF, allowing it to protect neutrophil precursors without inducing their proliferation, which may result in less bone pain compared to G-CSF [431]. - Plinabulin's mechanism as a potent agent to mature dendritic cells and activate T-cells is being explored in combination with checkpoint inhibitors in various trials [358]. - Plinabulin significantly increased dendritic cell MHC-II expression and T-cell infiltration in tumors [490]. Competitive Landscape and Intellectual Property - The company faces competition from large pharmaceutical and biotechnology companies, including Bristol-Myers Squibb and Merck, which market PD-1 inhibitors for cancer treatment [529]. - As of April 23, 2021, the company owned or co-owned 81 patents across 37 jurisdictions, including 19 issued U.S. patents [518]. - The patent portfolio includes 17 issued U.S. patents related to Plinabulin, covering its composition, synthesis, and treatment methods for various disorders, with expiration dates ranging from 2021 to 2036 [519]. - The company plans to seek patent term extensions for one of its U.S. patents directed to Plinabulin, which could extend the patent term by up to five years following FDA approval [520]. Future Plans and Strategic Direction - The company plans to either partner with national pharmaceutical companies or build its own sales force to commercialize Plinabulin in China and the U.S. [401][402]. - The company plans to advance one preclinical immuno-oncology agent into clinical development annually, starting with BPI-002 in 2022 [392]. - The company is exploring molecular glue technology to target dysfunctional proteins, although other companies are also pursuing similar approaches [533].