Rezolute Guggenheim 3rd Annual Healthcare Innovation Conference

Sure. Happy to do so, Debjit. Thanks again for having us. I think the brief introduction to our story is that we are a late-stage ultra-rare disease company, in the metabolic space, focused on treating refractory hypoglycemia associated with hyperinsulinism. In that space, we have two programs, one for congenital hyperinsulinism and the other for tumor-associated hyperinsulinism. Our therapy is a fully human monoclonal antibody that is designed as the first therapy to treat all forms of hyperinsulinism. While we're focused initially on tumor and on congenital forms of hyperinsulinism, we believe that our antibody's effective across the range and spectrum of all forms of refractory hypoglycemia associated with hyperinsulinism. That includes things like post-surgery, GI surgery.

Really happy and excited that we've completed phase III for the congenital indication, and that we are now on the cusp of actually announcing top-line results for phase III for the tumor indication.

Absolutely. The short answer is, and I think this speaks volumes to, we can talk a lot about the FDA and talk a lot about public health and talk a lot about rare disease. For the tumor indication, to level set for everyone, especially those who are new to the story, we're talking about often patients who are suffering with malignant tumors and who have entered and exited the hospital multiple times because of their hypoglycemia, because their tumor is over-stimulating the insulin receptor, and their hypoglycemia prevents their ability to take radioactive label therapies like LUTATHERA. They've been either surgery eligible or non-surgery eligible, and unfortunately, as their hypoglycemia progresses, it can often lead to a state where nothing can be done for weeks or months other than an IV glucose drip and then eventually hospice.

What we've seen as we've been treating patients now for three years through our expanded access program is, as we have worked with the FDA, because every single time an investigator, whether they're in Florida, New York, or in Oregon, they have to ask the FDA for permission to get our drug, and then we provide the drug. And every single time, we've seen a profound change in outcomes for these individuals' lives. The FDA's been witness to that as well. So, if we just back up 14 months ago, the FDA changed our phase III study design, in concert with us, of course, to streamline it so that we could have a very simple study to have a single arm, open label, to expedite the actual regulatory pathway.

Because as long as we can replicate what we've all seen in the real world, then this drug should be approved. And the FDA's been very clear about the need and the unmet need, in which we all know. No one wants to see someone who is suffering with cancer have to have hypoglycemia of this state and then pass away. So, the question is it approvable with a single-arm study? Absolutely, because that's exactly what the FDA wants, and because of this massive unmet need.

Happy to do so. On the congenital side, to bring back some hard memories for you, Debjit, and for all of us, a year ago, we were very surprised with the placebo response that we saw in our sunRIZE study in phase III, which was completely a confounder. Fortunately, the FDA agreed with us last March. They recognized that our primary endpoint, which was finger stick, self-monitored blood glucose, that that endpoint itself was a confounder, and that human behavior from parents and caregivers can significantly influence what study results may look like. And fortunately, the FDA said, "We hear you. We understand. Can you provide us the CGM data?" So, with those snapshots every couple of minutes, 24 hours a day, that detailed data was very When you mine that data, it's very compelling, we believe, what you see, which is a 50%-75% difference, at worst-case scenario, between placebo and each of the treatment arms.

So, we provided 500 tables, all of the raw data to the agency over the summer. They reviewed that data, and then about a month ago, they came back and said, "We understand. We're not telling you the drug's approvable, but what we are telling you is you should move forward with your BLA process." And that is, we believe, very compelling because we believe that the agency recognizes that, one, the unmet need in this patient population, like tumor, is massive for the children and their families.

And two, we believe they see what we see, which is there's clearly strong signs of efficacy, and we all know the history of the drug. We've been treating children now for more than, again, three years. Some children have been on their maintenance dose every month now for an extended period of time. Even out of the sunRIZE study, where we have open-label extension, for some of the children, it's been several years. They take their monthly maintenance dose. Some of the children are completely managing their hypoglycemia purely by using our drug, ersodetug.

All of that body of evidence, and this is where we get to the point of responsible drug development, and when a sponsor and the agency work together, I think we're seeing movement now within FDA, recognizing this in rare disease, where when the evidence gives you an indication of what the path forward should be, we should take it. This is, I think, a perfect example of being able to do that. We're very emboldened, very emboldened now to be prepared to file a BLA next year for congenital. The latter part of your question of why would we wait to request the meeting is that this is an unusual setup.