vTv Therapeutics Inc. Class A Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Yeah. Sure. I will kick it off. Emily, thank you so much for the invitation. It is good to be back. Really appreciate you inviting us. So vTv is a publicly listed, late-stage clinical biopharma company. Our lead asset is a drug called cadisegliatin, or CADI for short, which is basically being studied in phase III for the treatment of type 1 diabetes. Type 1 diabetes impacts 1.5 million people in the U.S., and 75% of the 1.5 million people living with T1D do not get to hemoglobin A1c of 7 or below, which is the recommended target that the American Diabetes Association recommends. There has been nothing new on the adjunctive treatment side for type 1 diabetics in over a century, when insulin was first discovered. So there is a massive unmet medical need out there. We have an experienced leadership team.

We have guided to completing enrollment of our phase III CATT1 trial in the third quarter, so stay tuned in the coming weeks, and that would lead to a readout of the top line data in 2027. On the financial side, we are well-financed through that top line data. That is a quick summary on the company.

Yeah. Glad to do that. Glucokinase is really an important enzyme in our body. It is expressed in many tissues. Its most prominent function in most tissues outside the liver is just to sense the amount of glucose that is circulating and directing the host cells, if you like, to then adjust their secretion patterns of hormones in the pancreas. Insulin expressing cells, the beta cells, as well as glucagon expressing cells, the alpha cells, determine their secretion of glucagon and insulin based on glucokinase signals, basically telling them how much glucose is out there. One important organ in our body is the liver, often overlooked. In people with type 1 diabetes, that organ does not fully function because the glucokinase in the liver is dependent on exposure to insulin. As you all know, in type 1 diabetes, beta cells no longer secrete insulin.

With the drop in insulin exposure, which cannot be fully replaced with exogenous insulin injections, the glucokinase levels drop, and thus the liver is impaired to really take care of business when it comes to managing glucose. The liver is really important in this sense because glucokinase is much higher, much more expressed in the liver, and that is because it is not only a sensor there, it is also a trench worker. It basically helps the liver to keep glucose that rises after meals in the organ, and a good part of that is being transformed to glycogen. The liver stores about one third of the body's glycogen reserves, which are required when you experience low blood glucose levels, and so the liver is being told, "Now we need to replenish glucose levels." So it is a really critical organ to maintain normal glucose metabolism.

All glucokinase activators, literally as the word implies, work by activating glucokinase. They bind to the glucokinase molecule and they make it work a bit harder, so it basically can process more glucose than it normally would do. In the past, glucokinase activators were non-selective. They were activating glucokinase in the pancreas, in other organs, and of course, in the liver as well. Also initially, glucokinase activators were almost exclusively developed for type 2 diabetes patients. The problem with that is that in the pancreas, on the beta cells, glucokinase activators were working basically like any other secretagogue. It was turning on insulin secretion, but it was not glucose regulated, so people actually experienced hypoglycemia. In the liver, the same happened because it was also often these activators were interfering with what is exclusive to the liver.

There is a feedback mechanism that up or down regulates glucokinase activity. When molecules like glucokinase activators interfere with that, it can be turned on permanently, and again, it leads to potentially hypoglycemia, but also to overproduction of fat, because once the liver is full of glycogen, it switches to actually storing fat. That's the reason why many of the early generation glucokinase activators did not work really well, especially not long term. You get some loss of activity because the pancreas is being stimulated again and again.

Basically the same things that you see with sulfonylureas. Cadisegliatin is very different because, having learned from the sort of negative experiences, the design was to focus on the liver as the target organ to take advantage of the kind of feedback that you have in that organ only, and also, of course, because the liver has much more impact due to its capacity to, independent from insulin actually, absorb glucose and store it as glycogen. Cadisegliatin is designed to bind to very specific molecules on the liver cell, which is also used by other medicines, and that makes it liver selective. It will not bind outside the liver.

Yeah. Simplici-T1 was a phase II study, double-blind, randomized, placebo-controlled trial in patients with type 1 diabetes, and was a treat-to-target study. Patients were instructed to lower their glucose as much as possible to which ADA targets of good control. Most patients had CGM sensors. Some also had pumps. The study was conducted at a time in 2018 when maybe only half of patients usually in trials had pumps or CGM sensors. The key outcome was we could lower HbA1c, which was important, but I think more importantly, we actually noticed that the rate of hypoglycemia was reduced by 50%. Ultimately, FDA felt that it was a really important finding, leading us to receive breakthrough therapy status.