BeyondSpring R&D Day Unveils New Plinabulin Cancer Strategy and SEED Therapeutics Updates

On May 16, 2024, BeyondSpring Inc. (NASDAQ: BYSI), a clinical-stage global biopharmaceutical company, announced the hosting of a virtual Research and Development (R&D) Day focused on its leading asset Plinabulin. This event, which took place on May 15, 2024, featured key discussions on Plinabulin's potential applications in cancer therapies, particularly for patients who have not responded to PD-1/PD-L1 inhibitors. Additionally, updates were provided on SEED Therapeutics, which specializes in using a Target Protein Degradation (TPD) platform for creating innovative molecular glue drugs.

The R&D Day was led by notable Key Opinion Leaders (KOLs) including Dr. Trevor M. Feinstein from Piedmont Cancer Institute, Dr. Alberto Chiappori from Moffitt Cancer Center, and Dr. Steven Lin from MD Anderson Cancer Center, alongside BeyondSpring and SEED Therapeutics executives.

The discussions highlighted Plinabulin's promising anti-cancer properties and mechanisms, such as its ability to enhance dendritic cell (DC) maturation and T-cell activation by releasing the immune defense protein GEF-H1 from microtubules. Plinabulin has been well-tolerated in over 700 cancer patients across two successful phase 3 studies. Notably, in a phase 3 trial involving EGFR wild-type second and third-line non-small cell lung cancer (NSCLC), the combination of Plinabulin and docetaxel significantly improved overall survival (OS) across all subgroups, doubling the two-year and three-year OS rates compared to docetaxel alone.

Furthermore, a phase 1 study at MD Anderson demonstrated Plinabulin's effectiveness when combined with radiotherapy and a PD-1 inhibitor. This combination achieved a disease control rate exceeding 50% in multiple cancers that had progressed following PD-1/PD-L1 inhibitor therapy, including NSCLC, head and neck squamous cell carcinoma (HNSCC), and Hodgkin’s lymphoma.

The ongoing challenge in cancer treatment is that around 60% of patients eventually fail PD-1/PD-L1 inhibitor therapy, despite these inhibitors being approved for roughly 20 cancer indications and generating over $40 billion in annual sales. Plinabulin, with its potent DC maturation effect, holds the potential to address this unmet medical need by being combined with PD-1/PD-L1 inhibitors, radiation, or chemotherapy, potentially filling a crucial gap in cancer treatment for these patient populations.

Dr. Lan Huang, Co-Founder, Chairman, and CEO of BeyondSpring, emphasized that several Investigator-Initiated Trials (IIT) of Plinabulin are underway at top institutions in the U.S. and China, with preliminary results expected in the second half of 2024. These findings could further validate Plinabulin's mechanism of action, potentially paving the way for expanded partnerships and accelerated development.

Following Plinabulin's presentations, Dr. Huang discussed SEED Therapeutics, BeyondSpring's majority-owned subsidiary. SEED Therapeutics uses its TPD platform, named RITE3, to develop molecular glues targeting previously undruggable proteins. Unlike PROTAC platforms, molecular glues can target proteins without ligandable pockets, including unfolded proteins like Tau. SEED's RITE3 platform leverages weak basal interactions between E3 ligases and protein targets, leading to higher hit rates during high throughput screening.

SEED Therapeutics has a diverse pipeline with six internal and two partnered assets targeting oncology, neurodegeneration, immunology, and virology. SEED plans to file an Investigational New Drug (IND) application in early 2025 for its lead candidate, an oral RBM39 degrader aimed at specific cancers. The company is also progressing with oral molecular glues for central nervous system (CNS) indications, focusing on Tau.

Eli Lilly, a current investor and R&D collaborator, has provided upfront and milestone payments totaling up to $780 million, along with tiered royalties. SEED has achieved three milestones under this collaboration, showcasing the platform's potential.

Dr. James Tonra, President and CSO of SEED Therapeutics, expressed his excitement about SEED's progress and collaboration achievements. He noted the recognition of SEED's RITE3 platform in the recent "Nature Biotechnology" review article on molecular glues, highlighting the company's innovative approach and growing interest from potential partners.