Spero Therapeutics, Inc. (SPRO) September 2026 Conference Transcript

Good afternoon, everyone, and thank you for joining us at the 2026 H.C. Wainwright 28th Annual Global Investment Conference. My name is Dr. Jade Montgomery, an Associate Research Analyst at H.C. Wainwright, and I'm happy today to introduce our presenter for this session, Esther Rajav Belou, President and CEO of Sparrow Therapeutics. Esther?

Thanks, Jade, and thank you to the Healthcare Wainwright team for hosting us today. It's great to be here and to be having the opportunity to present the Sparrow Therapeutics story to you all. Before we get going, the obligatory forward-looking statements. So Sparrow Therapeutics, we are a clinical stage company focused on immune-mediated diseases. Our lead asset is an antibody called SP001. It's a third-gen FC-silent anti-CD40 ligand map with potential for development across a range of immune-mediated diseases. We're taking it forward in IgG4-related disease, immunoglobulin G4-related disease, which is a rare indication, and we'll cover the unmet need and why targeting CD40 ligand is an important unmet need in this indication. We have, we're a small team, but we have an experienced immunology-focused drug development team, as well as rheumatologists on staff, and we have a cash runway into the second half of 2029, which gives us a good cushion to deliver proof-of-concept data in our lead indication. So why are we so excited about SP001 for IgG4RD? SP001 targets CD40 ligand, which is a validated target with human proof of concept across several immune-mediated diseases. The preclinical and the phase 1b data that's generated around this asset demonstrates potential for best-in-class potency. And the disease area that we're going into, IgG4-related disease, it is a disease with a high degree of unmet need despite the first drug getting approved last year and a couple of other therapies in clinical development. And CD40 ligand is the only mechanism that's truly differentiated relative to the other drugs and agents that are in development. It targets both the innate and the adaptive immune pathways, which we believe will provide additional benefits to the disease biology that is not currently covered by B-cell-targeted agents. We also see opportunities to develop this drug in other areas, both rheumatological and non-rheum areas, including Sjogren's disease. So a little bit about the pathway here, immune-related diseases are complex involving multiple different mechanisms. For the indications that we're targeting, there are three cell types that make a meaningful difference. One is the antigen-presenting cells, the T-cells, and the B cells. And T cells carry the CD40 ligands that bind to the receptors both on the APCs and the B cells. And this binding essentially creates a ghost signal that then activate the APCs and also generate the B cells to proliferate and make pathogenic antibodies. So this interconnected biology helps explain why targeting one, the CD40 ligand, which sits upstream of the entire immune pathway, could present a broader therapeutic benefit than agents that are targeting just the right side or, yeah, just the left side of this page with the B cells. I'll walk you through a quick overview of the drug that we've enlicensed and provide a summary of the data that got us really excited to bring this drug in-house and continue developing it. So 001 is a third-gen, fully humanized FC-silent CD40 ligand map. It was designed to retain the favorable properties of a conventional monoclonal antibody while addressing some of the platelet-driven safety concerns associated with the first-gen anti-CD40 ligand targeting agents on the left side of this page. Its FC region is engineered to be silent with no detectable FC receptor or complement binding, and it preserves the FCRN interactions in an IgG-like half-life at the same time. This design is intended to combine the high affinity and selectivity with practical aspects of antibodies like the PK and manufacturing properties. So on this next slide, here you can see the antibody response data from a mouse model. And the study, it's an in vivo immune response assay. And you can see here that the mouse injected with the anti-KLH, the response and the immune suppression relative to another leading antibody that's in development. It was a head-to-head study, and you can see that at one meg per keg, 001 suppresses the immune system more than the three mechs per keg for the competing antibody. This slide summarizes the phase 1b trial that was run in a Chinese patient population for Sjogren's disease. It was a double-blind, placebo-controlled, multiple ascending dose study with about 30 patients tested in three different cohorts, about 10 patients at seven and a half mechs per keg, 15 mechs per keg, and 30 mechs per keg. And the patients were randomized, eight active to two placebo in each of these cohorts. The primary endpoint was safety and tolerability after four doses at week 16. And through, sorry, safety and tolerability, and then follow-up through week 24. Secondary endpoint was PK and immunogenicity at week 24. And the study also measured changes from baseline to the end of treatment at week 16 for two of the endpoints, S-Di and S-Pri, in Sjogren's disease. The antibody was well-tolerated with no SAEs, and AEs were largely balanced across the treatment and placebo arms. And here you can see the response in disease activity in Sjogren's patients across the different doses that were tested, as well as placebo. On the left two panels, S-Di and S-Pri, you can see the colored bars. The patients showed meaningful improvement, dose-dependent response, and the purple bars on the placebo show worsening of disease scores. Similarly, the rheumatoid factor, which is a classic autoantibody marker also shows good response in the treated patient population and a positive change from baseline in the placebo, in the purple bar. This slide provides a cross-trial comparison across multiple different Asians that are in development for Sjogren's disease. And you can see here that SP001, after four doses at week 16, showed a more meaningful response in moderate to severe patients on the STI measurement relative to the other agents that were dosed over a six-month period. So this really, you know, speaks to the potential for potency relative to other agents and development in this patient population. Overall, the data to date support continued development for the drug. We looked at preclinical as well as phase one healthy volunteer trials and the phase 1b Sjogren study all support a good safety and efficacy profile. We saw linear PK across all doses, and the half-life was approximately 28 days supporting once-month dosing. The immunogenicity rate was also low at about 4% in the phase 1B in Sjogren's. So in the next section, I'll quickly walk you through an overview of IgG4-related disease and our planned path forward with SP001 for this indication. Immunoglobulin G4-related disease is a chronic immune-driven condition. The immune system attacks the body's own tissue, and over time, the inflammation causes scarring and fibrosis. Left undertreated, these patients progress to organ failure over time. And you can see on the image on the right that the disease is manifested across almost several different organs, and this manifestation can happen in multiple organs at the same time. There are an estimated 20,000 to 40,000 patients diagnosed in the U.S., and unfortunately, about 60% of patients present with organ damage at the time of diagnosis. This is a male-dominated disease with Asia-fonset typically at 50 to 70 years, and it's primarily treated by rheumatologists and immunologists. In the current treatment paradigm, it's a cycle of treatment, remission, and relapse. Patients typically are monitored until they have active disease flares, and at that time, patients are treated with steroids, plus or minus DMARGs. And if the flares are not controlled with the first line of treatment, they progress to biologics. Rituximab is often used off-label as a B-cell depleter. And then the first drug for this patient group was approved last year, a drug called Uplizna, which is used on-label now. Patients are typically, it's a it's a whack-a-mole approach. Patients are typically treated with the B-cell depleter, and then they're monitored until the next flare occurs when they're treated again. And what we're trying to do is provide a differentiated mechanism that essentially enables the physicians to manage these patients in a chronic and predictable manner. So you can see here that the development landscape, I'll draw your attention to the middle column there with the mechanism of action. The first approved drug, which is Amgen's CD19, is a B-cell depleter. And the two other agents that are in development are both targeting B-cells, both B-cell inhibitors. Sparrow with SP001 attempts to work upstream of the B cells and addresses both the T cell aspect of the disease and the B cell. And as I mentioned before, what we hope targeting this mechanism enables us to do is achieve greater flare reduction than the B cell inhibitors, potentially provide a more tolerable profile than the B cell depletors and address potentially the underlying fibrosis in addition to managing the flares in these patients. A little bit about the biological rationale. We covered this in the prior slides, but really, you know, we can talk to the role of CD40 ligand on this slide. the disease burden is in addition to the proliferating b-cells the disease burden can also be attributed to the t-cells and macrophages and all of these releasing inflammatory cytokines and profibrotic signals what we hope the targeting cd-40 ligand which sits upstream of the B cells, theoretically, could turn down several sources of pathology at once, including the antibody production, antigen presentation, as well as the fibrotic signals. Importantly, for IgG4 patients, there is evidence that T cells express CD40 ligands, and both CD40 and its ligand are elevated in IgG4-related diseases. So we are really excited about bringing this mechanism as a potential treatment option for these patients. And this slide lays out our clinical study plan. Our proposed phase two study design subject to discussions with the regulators is intended to establish proof of concept in this indication. We are planning to have two arms with two doses. It's an open-label trial. with a treatment duration of about 24 weeks, so six consecutive monthly doses. And we intend to enroll patients on steroids and off steroids and have a steroid tapering regimen incorporated in the trial design. We're planning to enroll patients that have organ manifestation in more than one organ and have active disease at the time of enrollment. The primary endpoint is change from baseline and IgG4 responder index at week 24. And we'll also measure safety and adverse event profile for this drug as secondary endpoints. And we've guided to initiating this trial in the second quarter of 2027. So with that, you know, I'll summarize by saying we're really excited about the asset, the data that we reviewed prior to in-licensing this from Innoven Biologics, and really excited about the path forward for this drug, both an IgG4-related disease and also other immunological conditions over time. So with that, I will open it up to any questions and I thank you for your time.