Bausch + Lomb Corporation Study result

Please go ahead. Great. Thank you, operator.

Thank you everyone for joining us on such short notice. We really appreciate you getting on the call today. I'm joined with my colleagues, Yehia Hashad, our head of R&D, and Maysa Attara, head of pharmaceutical R&D. We're looking forward to taking you through the presentation and, more importantly, taking any questions you have. Alison, if we could jump to the next slide. Perfect. Today we're sharing results on two first-in-class programs that further reinforces why we believe in our pipeline. First, on our dual action dry eye medicine. This is the first therapy designed to address both inflammatory and evaporative drivers of dry eye in a single treatment, and we will be moving it into phase III. As you'll learn later throughout this conference call, phase II showed a strong statistical significant effect at day 15, much faster than we expected.

That gives us a clear primary endpoint and a focused design as we advance. Second, on BL1332, our lead ocular surface pain candidate just delivered convincing clinical validation of the TRPV1 mechanism in humans. The result strengthens our confidence heading into phase II readout, which we expect coming in a few months. It opens the door to a broader franchise in ocular pain beyond post-surgical indications. When taken together, these two first-in-class assets represent more than $2 billion in combined potential peak sales, meaningful upside for us beyond 2028. I'll let Yehia and Maysa walk through the data, but I think the headline is simple. Both programs are going to move forward with conviction. Yehia, I'll turn it over to you.

Thank you, Brent. Good afternoon, everyone. We are really excited to report about these two programs. We will start with the dual action. Before we dive into the details of the data, I really would like to lead with some of the key takeaways for this program. Obviously, dry eye disease is a multifactorial disease, yet today's therapy generally address one of the driver at a time. This study validates our goal to bring complementary mechanisms together in a single treatment through a novel differentiated formulation that can deliver a high therapeutic effect with a less dosing concepts. The study have revealed a highly encouraging insights. The dual action eye drops demonstrated a superior effect earlier than what we anticipated, with a strong result at a pre-specified day 15 assessment. Those effects were achieved with lower lifitegrast volume and reduced dosing frequency, supporting the differentiated profile we envisioned.

We are advancing to phase III with greater conviction, a clearer endpoint strategy, and a focused development path. With that, I would like to hand over to my colleague, Maysa, who will walk you through the details of the study results.

Maysa? Great. Thanks, Yehia. Hello, everyone.

I am thrilled to share our clinical results for our novel dual action dry eye drop. Let's first start with our program strategy. Dry eye is a complex multifactorial disease. Patients experience similar symptoms, but with different underlying causes. Pure evaporation and ocular surface inflammation are two important disease drivers. At Bausch + Lomb, we have two therapies whose pivotal trials each demonstrated treatment of both the signs and symptoms of dry eye. Their active ingredients work through different mechanisms. We believe in combination, they will deliver superior results. MIEBO forms a monolayer that reduces tear evaporation, while lifitegrast, the active ingredient in XIIDRA, penetrates tissue to act as an anti-inflammatory. Combination products face steep formulation and clinical development challenges. That is why dry eye patients and eye care practitioners do not have one on the market today.

It is for this reason we see a clear opportunity to change that. Combining the XIIDRA and MIEBO active ingredients into the first dual action dry eyes therapy, simplifying treatment for eye care professionals and delivering better outcomes for patients. Our scientists have cleared the first hurdle by formulating the proven active ingredients in MIEBO and XIIDRA together in a single eye drop, and they have demonstrated those benefits of that combination in non-clinical models. On the left, you see non-clinical pharmacokinetic data comparing how much better lifitegrast, the active in XIIDRA, penetrates ocular tissues when formulated with the MIEBO active ingredient. This matters because lifitegrast needs to penetrate ocular tissues to work as an anti-inflammatory. Drug development breakthroughs often come from finding a way to deliver the lowest effective dose.

With this formulation, lifitegrast reaches the cornea and conjunctiva to ocular surface tissues damaged by dry eye far more efficiently. This drug delivery efficiency is what led us explore in this current clinical study, reducing both the total lifitegrast dose relative to XIIDRA and the dosing frequency relative to MIEBO, aiming to deliver two complementary mechanisms of action in a single, safe, well-tolerated product. Before we get to the results, it is worth pausing on how we dose this novel drug product. The dual action drop delivered lifitegrast in about a third of the drop volume used in the lifitegrast alone arm. That is 12 microliters of dual action drop versus 35 microliters of XIIDRA. We dose the dual action drop twice daily, so half as often as the PFHO alone arm, since MIEBO is indicated for use four times a day.

Everything you are about to see, we achieved with meaningfully less drug and less frequent dosing relative to the respective monotherapy. Okay, onto the study design. This was a 4-week randomized, double-mask, active-controlled study, and the first time we tested our assumptions regarding the dual action drop's performance in humans. 443 patients were randomized across six arms. The design included three active arms for statistical comparison and three matched vehicle controls for masking. Our pre-specified primary endpoint was changed from baseline in total corneal fluorescein staining at day 29 versus lifitegrast alone. We chose day 29 because with no prior human data on this dual-action drop, we set our primary time point earlier than the sign endpoint used in either monotherapy's own pivotal trial. We anticipated that combining these two mechanisms would produce a faster effect.

Before looking at outcomes, it matters that patients enrolled across the study arms started in the same place. Corneal staining and symptom scores were well-matched at baseline, and patients came in with moderate to severe disease, consistent with a registration quality dry eye patient population. Additionally, other baseline characteristics and demographics were assessed and found to be consistent across arms. Okay. Now to the exciting part, the efficacy data. Let's start with total corneal fluorescein staining, a sign doctors use to evaluate the health of the cornea. The lower the staining, the healthier the ocular surface. To begin, the study did not meet its day 29 primary endpoint versus lifitegrast alone. While numerically better, it was not statistically significant.

I wanted to lead with that, because what we learned is the superior effect of the dual action drop is actually faster and evident much earlier than day 29. Here is why we are confident. As early as day 8, the dual action drop was already pulling ahead of both monotherapies. At the pre-specified day 15 time point, it showed a significant reduction in corneal staining versus lifitegrast alone, with a P value of 0.0007. That gap narrowed by day 29, but not because our effect went away. The dual action drop's results held steady between the two time points. It narrowed because lifitegrast alone kept improving, which is not surprising. XIIDRA is itself an approved efficacious drug. Ultimately, what we learned was that the dual action eye drop had a rapid onset of effect, and now we have data to guide when to look for that effect in future studies.

Now let's further evaluate the meaningfulness of this improvement in corneal staining through a responder analysis. We see 41.6% of dual action drop-treated patients achieved a clinically meaningful 3-unit improvement in corneal staining by day 15, more than double the 18.8% treated with lifitegrast alone and ahead of the 31.6 treated with PFHO alone, even though PFHO was dosed twice as often. This result translates the group averages you just saw on the previous slide into individual patients, and more of them experienced a meaningful improvement in corneal health with the dual action drop than with either of the monotherapies. Again, this was at a fraction of the dose of XIIDRA and less frequent dosing than MIEBO. Now let's examine another responder analysis that tells us how patients feel on day 15.