BeyondSpring (BYSI) business update, September 29, 2026 transcript

Thank you. You may now begin. Good morning, everyone, and thank you for joining today's call. Before we begin, I would like to remind listeners that remarks made on today's call may reflect forward-looking statements that are related to such matters as BeyondSpring's clinical and pre-clinical research and development activities and results, regulatory and commercial plans, industry trends, market potential, financial, collaborative initiatives, and financial projections, among others.

While management believes that its assumptions, expectations, and projections are reasonable in view of the currently available information, you are cautioned not to place undue reliance on these forward-looking statements. The company's actual results may differ materially from those discussed during this call for a variety of reasons. including those described in the forward-looking statements and risk factor sections of the company's 10K and other filings with the SEC, which are available on the investor section of the BeyondSpring's website.

Joining me today, our chairman, Dr. Lan Huang, our chief executive officer, Mr. Ming Cho, and our chief scientific officer, Dr. Jun Liu. I will now turn the call over to our chairman. Lan, please go ahead.

Thank you, Cedric. Good morning, everyone, and thank you for joining us today. First, let me briefly introduce BeyondSpring Inc, which was founded in 2010, is headquartered in New Jersey, and was listed in NASDAQ in 2017. BeyondSpring holds an equity interest in Seed Therapeutics, which is a clinical stage molecular group company with investments from global pharmaceutical companies, Eli Lilly and Aci. In addition, we are developing a first-in-class anti-cancer small molecule agent, penabalin, which has composition matter pattern protection through 2036 in over 40 jurisdictions with potential to extend to 2041 based on Hatch-Wexman rule. Penabalin has extensive safety package. More than 700 cancer patients have been treated with penabalin. We plan to initiate Dublin IV, a conformative phase III study in second-line, third-line, Lung squamous, lung muscle lung cancer, post-immune checkpoint inhibitors, or ICI, a 442 patient study with OS as the primary endpoint.

We believe this study to be supported by its unique mechanism and the previous encouraging clinical evidence. This is a patient population with significant unmet medical needs. Recently, 12 Phase III studies have failed to demonstrate an OS benefit over docetaxel, the current standard of care. Penabalin combined with docetaxel demonstrated OS benefit versus docetaxel in a Phase III study in non-sponsor lung cancer, Dublin III, which was published in the Lancet Respiratory Medicine in 2024. Learning from Dublin III, we have designed Dublin IV to focus on penabillin mechanism-targeted lung, small cell lung cancer patients. Today, we are excited to share with you the news that the FDA has granted fast-track designation to penabillin plus docetaxel for the patient population being studied in Dublin 4.

In addition, we entered into a strategic transaction to receive access to clinical data from around 50% of the 442 patients planned for Dublin 4 by selling our ownership in greater China subsidiary. We believe this represents a more capital and execution-efficient path toward doubling-four interim analysis of 221 PFS events. After this strategic transaction, the BeyondSpring still owns global rights of penabillin outside of Greater China. Today, we would like to explain the scientific and clinical rationale for Dublin 4, what the fast-track designation means for this program, and how the strategic transaction is expected to support this global Phase III study.

I will now turn the call over to our CEO, Ming, to begin the presentation. Ming, please go ahead.

Thank you, Lai. Good morning, everyone. As Lai mentioned, today I will focus on two important developments for BeyondSpring and our Dublin 4 program. The FDA fast track designation and strategic transaction related to the China portion of Dublin 4. I will first outline the key messages, then turn the presentation over to Jun Lu, our chief scientific officer, to review the unmet need, the mechanistic rationale for penobillin, and the clinical evidence supporting Dublin IV. After that, I will return to review the Dublin IV study design and summarize the path forward for penobillin and Dublin IV.

Let me begin with a key takeaway from today's update. We have two important developments that we believe strengthen the path forward for Dublin 4. First, the FDA has guaranteed faster track designation for penobillin plus dorsetaxel for the same patient population being started in Dublin 4. Second and third line non-squamers, NACLC, following ICI treatment and platinum-based chemotherapy, and without actionable galamic alterations.

The designation provides opportunities for more frequent interaction with the FDA during development and may allow rolling review of a future regulatory application, as well as potential eligibility for priority review if applicable criteria are met.

Second, we have entered into a strategic transaction involving the sale of our Great China subsidiary interest to Biolin Investment Limited. Under this arrangement, BeyondSpring expects to receive access to clinical data from approximately 50% of the planned 442 patients in Dublin 4, supporting progress towards the study's interim analysis. Importantly, BeyondSpring continues to return the global rights to penoblin outside Great China. Together, these two developments are designed to improve the capital and execution efficiency of Dublin IV and advance the study toward its next major clinical milestone the pre interim analysis at 221 PSS events With that overview, I will now turn it over to Jun, our chief scientific officer, to review the unmet need, the mechanistic rationale for penoblin, and the clinical evidence supporting Dublin IV.

Jun, please go ahead.

Thank you, Ming. I would like to expand on what Lang and Ming just mentioned about the clinical need and the patient population that Dublin IV is designed to address. Immute checkpoint inhibitors, or ICIs, have become a major part of the standard care for treatment of non-small cell lung cancer. However, almost 60% of the patients eventually progress after ICI treatment. For patients who do not have actionable genomic alteration or commonly referred to as driver-native, treatment options are limited once they progress after frontline ICI and platinum-based chemotherapy. In this setting, docetaxel remains an important standard treatment option. However, historic outcomes with docetaxel remain modest, with median overall survival of approximately 9 to 11 months, and significant hematologic toxicity, including over 40% severe neutropenia.

which may limit dose-effects of dose intensity and treatment duration. Importantly, 12 phase 3 studies using different treatment approaches, including 8 PD-1, PD-L1 inhibitor combinations, and the four-antibody drug conjugate monothelapies in similar patient populations have failed to demonstrate an overall survival extension beyond docetaxel. This highlights the significant unmet need in the post-ICI study. Based on our projections, the post-ICI target population across the U. S. and the five major European markets of Germany, France, the United Kingdom, Italy, and Spain could reach approximately 135,000 patients in 2037 at the projected peak sales if approved, which represents a meaningful patient population that Dublin IV is designed to address.

Before reviewing the clinical data, I would like to first highlight the mechanistic rationale for palabilin in the post-ICI setting. First is the structural basis of plabalin as a first-in-class fast-off microtubule destabilizer with a distinct mechanism and a tolerability profile differentiated from other microtubule targeting agents on the market, such as taxing Eriblin and Vincus. Researchers now know that microtubules are not just structural elements of the cells, but also serve as dynamic sensors in response to stress signals. Palabolin's interaction with microtubules triggers the release of guanine nucleotide exchange factor GFH1, a key signaling protein that drives dendritic cell or DC maturation, antigen-preventing cell or APC activation, and a subsequent antitumular immune response. This is especially the case when palabilin is combined with standard-of-care chemotherapy or radiation that induces real-time tumor cell death and the release of tumor neuroantigens.

In other words, palabalins in new modulatory effect improves tumor energy presentation that is necessary for sustained tumor-specific T cell response to help overcome ICI resistance. We have early clinical data that Palabalin also modulates tumor vasculature, which provides additional mechanistic rationale for going after non-squamous lung small cell lung cancer where anti-VEGF drugs are used.

Finally, prolabolin has demonstrated neutropenia mitigating activity, which may help support chemotherapy dose intensity and treatment continuity. Together, these complementary mechanisms provide a biological rationale for evaluating prolabolin-containing regimens in the post-ICI setting.

Let me now turn to the clinical evidence supporting this rationale. Dublin IV is supported by encouraging clinical evidence from our Dublin III study, together with the prospective data from study 303.

First, in the overall Dublin III Phase III population of intention to treat 559 patients in second and third-line EGFY-type lung small cell lung cancer with one-to-one randomization. Clablum plus docetaxel demonstrated a statistically significant overall survival benefit with a hazard ratio of 0.82. We also observed a long-term survival benefit with higher 24- and 36-month survival rate than docetaxel alone.

Second, in a non-squamous population of 332 patients, which is more relevant to Dublin IV, the observed overall survival hazard ratio was 0.72, with a median extension of approximately 2.5 months.

Third, a post-hoc analysis of Dublin III revealed an encouraging efficacy signal in the post-ICI subgroup. The median overall survival was 15.8 months with palabalin plus docetaxel, compared to 11.7 months with docetaxel alone. The median progression-free survival, or PFS, was 5.6 months versus 3.8 months, and the objective response rate, or ORR, was 18.2% versus 8%. In addition, Study 303 evaluated a palabaline-containing regimen with docetaxel in the post-ICI setting. It reported a median PFS of 7.0 months, an ORR of 18%, a disease control rate of approximately This data suggests a more durable tumor response compared to docetaxel in similar patient populations as reported in Eutropia lung 1 and COSTAR phase 3 studies. Taken together, the Dublin-3 subgroup findings and the results from study 303 provide a clinical rationale for evaluating Dublin-4 in a more clearly defined, And the BeyondSpring Inc Palabalin Mechanism Supported Population of Patients with Non Non Cell Lung Cancer whose disease has progressed following ICI treatment With that I will turn it back to Ming to review the Dublin IV study design and discuss how we plan to execute the program Ming please go ahead Ming Wang Thank you, Jun.

Let me now briefly review the design of Dublin IV. Doubling 4 is a complementary global phase 3 study in post-ICI, driver-negative, non-squamous, and NACLC. Approximately, 442 patients are planned to be enrolled. Patients will be randomized one-to-one in the double-blind design. The experimental arm receives dastaxel plus penoblin, while the control arm receives dastaxel plus placebo. OS is the primary endpoint, with PFS, ORR, and other important clinical and safety measures also included in the study. Approximately, half of the planned enrollment is expected from China, and approximately half from Western regions. BeyondSpring brings several execution capabilities to this program, including global oncology and regulatory experience, experience completing phase three studies, an established The clinical site and investigator network and direct operational experience from Dublin 3.

Our currently disclosed development timeline shows starting initiation around the end of 2026 to early 2027, with the interim analysis expected in 2028. As interim analysis is event-driven, its timing will depend on enrollment and the accumulation of PFS events.

Let me close by bringing these elements together and highlighting what we believe creates a clear path to wide curation for penobillin. First, we have a differentiated clinical stage asset supported by a substantial body of scientific and clinical evidence. More than 700 cancer patients have been treated with penoblin across multiple clinical programs, providing an extensive clinical safety database. In Dublin III, Pernoblin plus dorsetaxel demonstrated a statistically significant OAS benefit, and its differentiated JSH1 mechanism provides both immunomodulatory activity and the potential to mitigate chemotherapy-induced neutropenia.

Second, we believe doubling four provides a focus path to confirm these clinical benefits in the mechanism targeted post-ICI non-squamous NSCLC population. Importantly, the FDA fast track designation and our strategic transaction related to the China portion of doubling four are expected to strengthen both the regulatory and execution framework for the program. Based on our current development timeline, the pre-specified interim analysis is expected in 2028, subject to enrollment and accumulation of the required PFS events.

Finally, we believe Dublin 4 addresses a large and underserved post-ICI NSCLC patient population, And if successful, could establish a meaningful commercial opportunity for penoblin and unlock penoblin's potential as a differentiated anti-cancel agent in NSCLC and beyond.

Taken together, we believe the clinical evidence, differentiated mechanism, focused phase three strategy, and recent regulatory and strategic development provide a clear path towards the next major value-creating milestones for penoblin and BeyondSpring. Our focus now is on displaying execution of Dublin IV, and as one thing the program towards its pre-specified interim analysis.

With that, I will turn the call back to Lange.

Thank you, Ming, and thank you, Jun. We believe this development represents important progress for BeyondSpring and Dublin 4. We remain focused on executing the global phase 3 program and advancing penambulant towards its next major clinical milestone.

With that, we're ready to take your questions. Operator, please open the line for Q&A.

Yeah, thank you, Sylvan. I think I'm going to turn the answers to Dr. Jun Liu, our CSO.

Yes, thank you for the question. This is Jun Lu. Yes, I agree with you that given the type of data out there, this is a challenging therapeutic space competing against docetaxel in post-ICI setting. I should also mention that in the recent COSTAR long phase 3 study, GenPurri or Dostolimab plus docetaxil did not surpass docetaxil in PFS and over the survival. But still, this space is very active with at least eight phase three studies, either ongoing or not yet recruiting, evaluating novel IO agents, ADCs, including those of novel targets by specific antibodies or by specific ADCs. So, to our end, we believe that palabinine's mechanism supports the Dublin IV program as the following.

First, as those attacks of cancer cells in the body, palabinine is there to drive imogenic DC maturation, breaking the immune tolerance, which is the key determinant to fully reverse T cell exhaustion. We also stacked the deck in our favor, so to speak, by enrolling only non-Springless patients based on the efficacy data we saw in Dublin-3, study 303 in post-ICI non-small-fear-long cancer patients, and the tumor vasculature effect of parabalans. Together with the same benefit of palabalins that allows them for more dosy types of dosing and a better bone marrow recovery, we think that palabalins helps to refresh and sustain the cancer immunity cycle for a more durable antitumor immune response to help overcome IO resistance.

Now, please come in.

Yeah, thank you, Joan. Yeah, Sylvan, you asked this great question. So we have been studying penabula for over 15 years in its immune modulating mechanism, and we believe that it differentiates DC maturation and also targeting vasculature. And finally, reducing chemotherapy neutropenia really is perfect to combine this profile to get into this Dublin IV population. And from the study design and also patient number we have worked with independent statisticians to use the Dublin III study data and also the OS has a ratio for non population and also the post hoc analysis in ICI progression patient to determine this 442 one randomization with a power of over 85 Yeah, thank you.

Yeah, great. Thank you. And maybe on the business side, did the FDA sign off on your Dublin 4 design and maybe the patient composition, right? So now you will have a significant number of Chinese patients and then rest of the world patients.

Did they sign off on it and specifically the 50-50 split that you can expect here at this trial?

So, yeah, if I can just start, and then Ming can come in into the split of Western and Asian population split. So, from a study design point of view, our Phase III protocol for Dublin IV has been aligned with FDA in this population, and also OS is the primary endpoint. And we are very honored to receive the fast track vaccination from FDA for this population. Secondly, of course, it's always good to have more Western patients, but depending on where the patient comes from, the speed and also cost efficiency, and also the support for the global study and the BAM package for the FDA approval, we actually utilize this 50-50 split. And they already have some examples before for this successful regulatory strategy.

Ming, you can talk about those examples.

Thank you, Lange. Thank you, Lange. Yeah, of course, there are also recent FDA approvals supported by programs with a substantial proportion of Asian patients. For example, the Neurantum Bells drug, TL3C-Pinid, was approved based in part on a study conducted in Thailand, China, together with a global study that also involved a high proportion of Asian patients. And also, a drug from D-Law called Salvo ZT-Need was approved based on a multinational study in which approximately 65% of the efficacy population was Asian.

But I think which is most important for us is that W-4 will apply the same protocol and evaluation standards across regions. PK and efficacy will be evaluated across Asian and Western populations to assess the consistency of drug exposure and treatment effect. So, yeah, I think we believe our approximately 50-50 strategy is reasonable. Of course, the ultimate acceptability of the data will depend on the actual study results and the FDA's review. Thank you.

Great, thank you. I'll hop back in the queue.

Yeah, so probably I can start, and then Ming can chime in. So as you see, this study is a 442-patient study with the presbyter interim at a 221 PFS event. So with this very important non-cash and also non-dilutive transaction with investors, then we are getting around 50% of the of the patient data, which is around, you know, 221 PFS events and OS events in the future. So that definitely cuts down on the cost for the BeyondSpring to generate data to get to the precipicide interim analysis, which is the 221 PFS events. So the actual how much to be saved, of course, it's going to be determined by the study operation. But as you see here, already more than half of the study cost is reduced.

And also, China has such a great population of non-small lung cancer patients, so the speed is also going to add to our arrival at the pre-specified interim analysis. Thank you for the great question.

Great. And sorry, one last one. So obviously, this is a small molecule, but it seems to do a lot of things. Maybe you can just summarize how I guess the mechanism of GFH1 kind of explains all of these, and how does that line up with some of the side effects that you've seen in Dublin 3, such as the GI side effects and the hypertension? Thank you.

Yes, hi. Yeah, so June will comment.

Yes, I very much welcome the in-depth question. We have been, as I mentioned, we have been building our knowledge base over the years. First, I want to mention that people only recently recognize the sensory role of microtubules that may be as important or more important than their traditional architectural role. According to a recent cell paper published by our collaborator, Dr. Michelle Stenmatz at the University of Basel, GFH1 is one of the key microtubule associated signaling proteins, but there are others that are not yet explored.

Second, its GAPH1 function is different in different cell types. Obviously, microtubules are everywhere, right? So, biologically, its activity is highly regulated through four phosphorylation sites, depending on the timing, location, and environmental cues. Under my suppressor condition, the bone marrow recovery or regenerative hematopoiesis is also a GFH1-dependent process. As far as the side effects you mentioned, GFH1 regulates better integrity in the intestines and normal vasculature. The GI side effect is managed in the clinic by medication. We actually consulted with Dr. Christian Alenica at UT Southwestern, who specializes in gastroenterology and gut health. He published in April this year that a lung isoform of GFH1 is located in intestinal artificial cells. So he believes that the prolabinase GI study effect may attribute to that.

As far as the hypertension, the hypertension is transient, which often resolves within four to six hours after infusion. This is because GFH1 is at a tight structure that its minor disturbance can cause transient endothelial disturbance. So, I hope that answers your question.

Yeah, thank you. Thank you for your questions and for joining us today. We appreciate your continued interest in BeyondSpring. We look forward to keeping you updated as we are the virus doubling for and the development of penobili to help patients with high-alpha medical needs. Thank you, and have a good day.