Spero Therapeutics, Inc. Common Stock Chardan's 10th Annual Healthcare Conference

Thanks for coming, Esther. Thank you for having us.

Sure. Thank you. Before I answer that question, I'll just refer you to our forward-looking statements, which you can find in our corporate deck. But really, Spero today, we are a development stage company, and we've always been a development stage company. Our lead asset, as you say, is SP001, which is an anti-CD40 ligand targeting antibody. It's a third-gen antibody, and we can get into why that's relevant. We're planning a phase II trial in immunoglobulin G4-related disease, planning to initiate that trial in the second quarter of 2027. Having gotten our first drug approved and out-licensed to GSK for commercialization. Also, we've also fundraised about $105 million in a non-dilutive, non-recourse partial monetization off those commercial milestones. We feel we're in a very good position to bring this new asset in and continue developing.

Sure. We find IgG4-RD to be a very compelling development opportunity. It is an indication that's fairly early in its life cycle. We think that the unmet need and the potential for a differentiated mechanism would be highly relevant to this treatment paradigm. Because, as you know, this indication, the first drug was approved just last year, and there are the other agents, the couple of other agents that are in development all focus on B cells, and we're moving upstream of that, targeting the CD40 ligand, and we think that potentially has the ability to cover aspects of the disease that are not appropriately being addressed by B cell targeting agents. Sjögren's is also highly attractive to us. Obviously, there is no approved therapy, especially in the West, for that indication.

Our partner, Innovent, is guided to initiating a phase II trial in Sjögren's by early 2027. The evidence for SP001 in Sjögren's will continue to evolve as we make progress in IgG4-RD.

Sure. Being a clinical stage company, our sort of search parameters were focused on validated targets or targets that at least had partial validation in the clinic. We were looking for molecules that had the potential to differentiate relative to other agents that are in development. The third aspect was really being able to differentiate with that target in evolving markets across different therapeutic areas. We were able to hit all of those with the CD40 ligand antibody that we in-licensed. As is typical in any BD process, we checked all the boxes. We looked at non-clinical and clinical data, IP, the regulatory interactions that Innovent had had, CMC quality. Very typical of a process like this.

Yeah. The history of the target was something that we spent a lot of time thinking about. The first-gen molecules, the first-gen antibodies had an active Fc region, which led to the thrombotic events that we saw in the first trials that were ran, I believe, in lupus. SP001 has a fully silent Fc region, and the antibody has been tested in two healthy volunteer trials in phase I, as well as a phase I-B Sjögren's trial. In approximately 100 plus human subjects that have been tested, we haven't seen any evidence of thrombotic events. Obviously, safety is something that we will continue to monitor very closely and will be a focus for our trials going forward.

Yeah. The phase II that we are planning to run in IgG4-RD will generate the evidence based on some of the data points that we are planning to collect in that trial. Really the onus is on us to provide the evidence on the role of T cells in IgG4-RD. There are some publications that discuss it, but for this particular antibody, our phase II would be very relevant. There is evidence that T cells play a role in the pathophysiology of IgG4-RD, and CD40 ligand sits upstream, and it is an upstream mediator of both the innate and the adaptive immune responses. We think both aspects of those immune responses play a role in the steady state of four IgG4-RD patients.

Our objective is to gather data points in the phase II trial that would really help us characterize the benefits of targeting CD40 ligand for this population, and that could include impact on fibrosis.