On May 16, 2024 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company focused on developing innovative cancer therapies, reported that it hosted a virtual Research and Development (R&D) Day to discuss its lead asset Plinabulin, a dendritic cell (DC) maturation agent, in drug combinations to potentially address the current unmet medical needs in cancer indications where patients failed prior PD-1/PD-L1 inhibitors, as well as updates for SEED Therapeutics which focuses on target protein degradation (TPD) platform for innovative molecular glue drug discovery on May 15, 2024 (Press release, BeyondSpring Pharmaceuticals, MAY 16, 2024, View Source;utm_medium=rss&utm_campaign=beyondspring-rd-day-highlights-new-plinabulin-development-strategy-for-cancer-and-updates-for-seed-therapeutics [SID1234643388]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The R&D Day was led by Key Opinion Leaders (KOLs) Trevor M. Feinstein, M.D. (Piedmont Cancer Institute), Alberto Chiappori, M.D. (Moffitt Cancer Center), and Steven Lin, M.D., Ph.D. (MD Anderson Cancer Center), as well as BeyondSpring and SEED Therapeutics management.

Invited KOLs shared their latest insights on plinabulin’s durable anti-cancer benefit, mechanism-of-action (MOA), and its unique potential as an I/O combination agent with chemotherapy or radiation, in patients that have progressed on PD-1/PD-L1 therapy. Over time, plinabulin may have the potential to move into earlier lines of treatment in combination with I/O:

As a unique tubulin binder, plinabulin drives dendritic cell (DC) maturation/T-cell activation by effectively liberating the immune defense protein GEF-H1 from microtubules.
Plinabulin alone or in combination has been well-tolerated in >700 cancer patients in two positive phase 3 studies.
In a phase 3 study with EGFR wild-type 2L/3L NSCLC, the combination of plinabulin and docetaxel significantly extended OS in all subgroup analyses and doubled 2-year and 3-year OS rates compared to docetaxel alone.
In an MD Anderson phase 1 study, in combination with radiotherapy and a PD-1 inhibitor, plinabulin demonstrated its DC maturation MOA in responding patients (PR+SD) in multiple cancers that had progressed during PD-1/PD-L1 inhibitor therapy with >50% disease control rate (PR+SD). The most responding cancers include NSCLC, HNSCC and Hodgkin’s lymphoma.
PD-1/PD-L1 inhibitors have been approved in approximately 20 cancer indications with >$40 billion annual sales, and yet around 60% of patients eventually fail, leaving them with limited treatment options.
Plinabulin’s potent DC maturation effect, in combination with PD-1/PD-L1 and radiation or chemotherapy, may address unmet medical needs across numerous patient settings following progression from PD-1/PD-L1 inhibitor therapy.
Plinabulin has the potential to fill a substantial gap in cancer treatment for precisely the same patient settings that have been found elusive to other mechanisms or combinations.
"Additionally, significant headway is being made through various Investigator-Initiated Trial (IIT) studies of plinabulin at leading institutions in the U.S. and China. Preliminary results are expected to be reported in 2H 2024, that are expected to reinforce our unique MOA and lead to a transformative year for BeyondSpring. If interim clinical data from our ongoing studies further validates our unique MOA, then we will look for opportunities to extend and accelerate plinabulin’s outreach through third-party partnerships," said Dr. Lan Huang, Co-Founder, Chairman and CEO of BeyondSpring.

Following the plinabulin presentations, Dr. Lan Huang discussed how BeyondSpring’s majority-owned subsidiary, SEED Therapeutics, uses its proprietary TPD platforms to develop "molecular glues" for undruggable targets. Different from PROTAC platforms, molecular glues have the potential advantage of targeting un-ligandable proteins, including proteins without ligandable pocket, and unfolded protein, such as Tau. The SEED TPD platform referred to as RITE3, has translated the scientific breakthroughs and insights of its co-founders, including a Nobel Laureate and two Howard Hughes Medical Institute investigators, into a diversified and fast-evolving drug development pipeline:

Differentiated from other molecular glue companies, which are mainly "E3 centric", SEED’s RITE3 platform is "target centric" and uses novel E3 ligases for protein targets. With detectable weak basal interaction between selected E3 and protein target, the binder hit rates from its high throughput screening is higher.
6 internal pipeline assets and 2 partnered assets, in oncology, neurodegeneration, immunology, and virology used 5 novel E3 ligases.
SEED expects to file an IND in early 2025 for its IND Candidate oral RBM39 degrader, for the treatment of rationally selected cancer indications.
SEED R&D has a focus on the development of orally delivered molecular glues for CNS indications, with a lead internal program against Tau.
Eli Lilly is a current investor and R&D collaborator with upfront and milestone payments up to $780 million, plus tiered royalties. SEED has achieved 3 milestones with Lilly R&D collaboration.

"I’m delighted to announce SEED’s substantial progress in advancing internal initiatives, including an oncology asset advancing towards first human dose in the first half of 2025, Tau degraders for neurodegeneration advancing towards lead molecule status towards the end of 2024. In addition, we have a synergistic collaboration with Eli Lilly, which achieved multiple milestone payments. In the recent "Nature Biotechnology" review article on molecular glues, it was truly a privilege for SEED Therapeutics to be recognized alongside other prominent companies employing groundbreaking TPD molecular glue strategies. Leveraging our unique and proprietary RITE3 platform that focuses on predicting, detecting, and utilizing a pre-existing weak interaction between an E3 ligase and the target disease-causing protein, SEED consistently garners growing interest for additional partnerships and investment," said Dr. James Tonra, President and CSO of SEED Therapeutics.

An archived replay of the webinar will be available on BeyondSpring’s website www.beyondspringpharma.com under "Events and Presentations" in the Investors section.

Trevor M. Feinstein, M.D.
Dr. Feinstein is board certified in medical oncology and hematology. He joined Piedmont Cancer Institute in 2011 and is the Director of Research at Piedmont Fayette Hospital. Dr. Feinstein is actively involved in clinical trials focused on improved therapies for various cancers. He is a member of Georgia CORE’s research committee along with Georgia Society for Clinical Oncology Clinical Practice Committee. He also chairs the Lung Disease Group for the entire OneOncology network. He is a co-investigator on several peer-reviewed research projects and has authored numerous publications and abstracts in Hematology and Oncology. Dr. Feinstein graduated from the University of Illinois medical school and completed his residence and fellowships at the University of Pittsburgh.

Alberto Chiappori, M.D.

Dr. Chiappori is board certified in medical oncology. He serves as senior member of oncology and medicine for the Thoracic Oncology Program at the H. Lee Moffitt Cancer Center and Research Institute in Tampa and Florida. Dr. Chiappori is an active member of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper), the American Association for Cancer Research (AACR) (Free AACR Whitepaper), and the International Association for the Study of Lung Cancer (IASLC). Dr. Chiappori received his M.D. from the Universidad Peruana Cayetano Heredia in Lima, Peru, completed his residency at Southern Illinois University School of Medicine in Springfield, Illinois, and finished his fellowship and senior fellowship in medical oncology-hematology at Vanderbilt University School of Medicine in Nashville, Tennessee.

Steven Lin, M.D., Ph.D.
Dr. Lin is a Professor and Physician-Scientist at MD Anderson Cancer Center, with joint appointments in the Departments of Radiation Oncology and Experimental Radiation Oncology. Dr. Lin’s practice focuses on thoracic malignancies, and he oversees several clinical trials including the use of proton beam therapy for esophageal cancer and in the combination of immunotherapy with radiotherapy in lung and esophageal cancers. Dr. Lin runs a translational research team that evaluates biomarkers for treatment response and disease outcomes after cancer therapy. Dr. Lin acquired his M.D. and Ph.D. in the Medical Scientist Training Program at the University of California Irvine Medical School. He went on for residency training in Radiation Oncology at The Johns Hopkins Hospital.