Inhibrx Biosciences, Inc. Common Stock Study update

Good morning, sir. Good morning, everyone.

I'm Mark Lappe, CEO and co-founder of Inhibrx. Throughout today's presentation, I'll be referencing a set of slides. These are accessible directly through the webcast window or available under the investor relations tab of our website. Before proceeding, I would like to remind you that during our call today, we will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements and other risks associated with our business can be found in our filings made with the SEC. These statements are based on our current beliefs and expectations, and we assume no obligation to update or revise these forward-looking statements as circumstances change, except as required by law. With those disclosures noted, let's get started. Today, I'm very excited to share what we believe is the most important clinical update we've had on INBRX-106.

We started this program with a very specific thesis. OX40 is an extraordinarily compelling target, but previous molecules were not able to activate it effectively enough in patients. We designed 106 to solve that problem, and today we believe the clinical data show that we have. What we're going to share is what we believe to be the first clear clinical validation of OX40 co-stimulation with an exceptional opportunity emerging in HPV positive head and neck cancer and a much broader opportunity beyond it. Let me start with the key takeaways on slide 3. First, we believe we've clinically validated OX40 as a therapeutic mechanism. INBRX-106 is the first OX40 agonist to demonstrate clear clinical activity as T-cell co-stimulatory therapy. In the randomized HexAgon head and neck study, 106 plus pembrolizumab achieved a confirmed objective response rate of 48.3%, compared with 26.5% for pembro alone, a 21.8 percentage point improvement.

We also see deeper responses, including four complete responses that we did not see with pembro alone and a meaningful improvement in six-month progression-free survival at 72.4% versus 42.8%. Second, the HPV positive data are exceptional. We see an 80% confirmed objective response rate versus 33% and a 30% complete response rate versus zero, 90% progression-free survival at six months versus 33%, and the median progression-free survival that has not yet been reached versus 4.6 months. We are expanding the phase II study, which we believe can support a potential accelerated regulatory path and a potential launch by the end of 2028 to early 2029. Third, we believe the HPV positive data are the first clinical expression of a much broader biological opportunity for 106.

The biology points us toward expansion in highly immunogenic tumors, and our ongoing perioperative lung cancer study is an important clinical test of that broader thesis. Lastly, combining with individualized cancer vaccines could ultimately become one of the largest opportunities for 106. This is supported by our HPV positive data demonstrating 106 is driven by antigenic recognition, not PD-L1 expression, and more than 20 years of academic research demonstrating that OX40 agonism can enhance vaccine-driven immune responses. As you think about 106, we see HPV positive head and neck cancer as the fastest path to market, but we believe it is only the beginning of the opportunity. Before we dive deeper into the clinical data, I want to spend a minute on the biology of 106 found on slide 4 because it explains both what we are seeing today and where we believe we are headed.

The simplest way to think about this is effective T-cell activation requires both recognition of the tumor and a strong co-stimulatory signal. The first step is what we call signal 1. The T-cell recognizes an antigen being presented by the tumor or an antigen-presenting cell. But antigen recognition alone is not enough. The T-cell also needs a second signal, co-stimulation, to drive a strong, sustained immune response. That is where OX40 comes in. OX40 co-stimulation is designed to amplify the T-cells that already recognize the tumor, increasing their proliferation, improving their survival, and promoting the formation of immune memory. At the same time, PD-1 signaling suppresses that response, so the combination is very intuitive. Pembro releases the brake and 106 steps on the accelerator. A number of major pharmaceutical companies have invested heavily in the OX40 target in the past, but all of those attempts were conventional bivalent antibodies.

However, OX40 is a receptor that depends on higher order clustering to generate a strong co-stimulatory signal. A bivalent antibody can engage the receptor, but it does not effectively bring enough OX40 molecules together to produce the level of signaling required for robust T-cell activation. In other words, the field may have had the right target, but the wrong molecular architecture. 106 is a hexavalent OX40 agonist, meaning it can engage multiple OX40 receptors simultaneously and drive the higher order clustering that we believe is required for potent co-stimulatory signaling. That distinction is fundamental to the 106 story. On the right side of slide 5, you can see the higher order clustering generated by 106 compared with the lower order clustering produced by a conventional bivalent format on the left.

That matters particularly in T-cell populations where OX40 expression may be relatively low, including CD8 positive T-cells, which are central to direct tumor cell killing. The HexAgon head and neck study was designed to test whether the biology we just discussed actually translates into meaningful clinical activity. On slide 6, we present the trial design. In the phase II portion, patients with first-line recurrent or metastatic head and neck cancer were randomized one to one between the combination arm and pembro alone. A head-to-head study gives us a very clean way to answer: what is the contribution of benefit from 106? What does 106 actually do, add? The primary endpoint is objective response rate with duration of response, six-month progression-free survival, and safety among the key secondary measures.

This study was also built from the beginning as a seamless phase II/III program, so we can move directly into the confirmatory portion without having to stop and start a completely new trial. Before we get into the efficacy results, I wanted to quickly discuss the baseline characteristics on slide seven. We had 33 patients randomized to 106 plus pembro and 35 to pembro alone. The key point here is the two randomized treatment arms were well-balanced across the major disease characteristics, including HPV status, disease status, ECOG performance status, and PD-L1 expression. Next, let's move on to safety found on slide eight. Given that 106 is designed to actively costimulate the immune system, we would expect to see some incremental immune-related toxicity when we add it to pembro.

The most common treatment-related adverse events with the combination were rash, fatigue, and diarrhea, and importantly, these events were predominantly grade 1 or grade 2. There were no grade 5 adverse events in the 106 plus pembro arm. There was no increase in pembro-induced pneumonitis and no meaningful increase in CRS. We do see a higher rate of treatment discontinuation with the combination, and these events were varied, with no single adverse event accounting for the difference. Importantly, after patients came off treatment, most either maintained their tumor response or remained stable. In some cases, we continue to see tumor reduction even after dosing had stopped. This also includes a few patients whose first response was documented after discontinuation. It's also important to mention that we did not see the same pattern in the patients that discontinued pembro.

Overall, we believe the combination has demonstrated a generally manageable and well-tolerated safety profile, supporting continued development of 106 in combination with pembro. Slide nine gives us direct biological validation in patients that 106 is doing exactly what it was designed to do. When we add 106 to pembro, we see up to a 15-fold increase in T cell proliferation and up to a four-fold increase in T cell activation compared with pembro alone. The magnitude of that separation is striking. Remember what we discussed earlier. Pembro releases the brake on the immune response, 106 is designed to step on the accelerator. This is the clinical evidence that the accelerator is working. 106 is not simply adding another antibody to pembro, it's materially changing the biology of the T cell response. Importantly, we see this in both CD4 positive and CD8 positive T cells.

CD8 T cells are particularly important because they are the effector cells responsible for directly recognizing and killing tumor cells. So before we even look at tumor response, we have direct pharmacodynamic evidence in patients that 106 is producing the costimulatory biology that we engineered the molecule to deliver. The next question is whether that substantial increase in T cell activity translates into better outcome for patients, and that is exactly what we see on the next slide. On slide 10, we see that the biological activity translates directly into clinical benefit. The primary endpoint of the Phase II study was confirmed objective response, or cORR. 106 plus pembro achieved a cORR of 48.3% compared to 26.5% for pembro alone. A 21.8% point improvement. So we are seeing substantially more patients respond when 106 is added to pembro. Importantly, it's not just the number of responses that is different.

When you look at the waterfall plot, you can see greater depth of tumor reduction in the combination arm. We observed four complete responses in the 106 plus pembro arm compared to none with pembro alone. That degree of depth is particularly encouraging, and it begins to connect all the pieces we've shown you so far. We engineered 106 to generate stronger OX40 signaling. We showed you direct evidence that it dramatically increases T cell proliferation and activation in patients. Now in a randomized study, we see that translate into substantial improvement in confirmed response rate and deeper tumor responses. The next question, of course, is whether those responses are durable, which we will look at on slide 11. This is where the data become even more compelling. At six months, 72.4% of patients receiving 106 plus pembro were progression-free, compared to 42.8% on pembro alone.