Ladies and gentlemen, it¡¯s a great honor for me to talk about tegoprazan, which is a new and strong acid blocker for the management of gastroesophageal reflux disease and peptic ulcers. I am Jun Haeng Lee, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea. Tegoprazan is a new potassium competitive acid blocker. It was developed in Korea and launched in the Korea 3 years ago. It quickly became the number 1 drug in the Korean market among medications for gastroesophageal reflux disease. Before the introduction of tegoprazan in the year 2019, PPIs have been the preferred medication for GERD. PPIs are prodrugs, so they need to be converted into an active forms. However, tegoprazan itself is an active drug, so it can directly bind to potassium binding domain of proton pumps not only in the resting state but also in the stimulated state. So, tegoprazan is much faster than PPIs. Tegoprazan has many advantages in the management of acid related diseases. Among them, I¡¯d like to tell you three benefits. Tegoprazan is potent, fast and long-acting. The most important aspect of tegoprazan is that it is potent. In the petagastrin-treated animal models, tegoprazan raised the intragastric pH more than 6 within an hour. In the clinical trials, 50 mg of tegorazan tablet, the red line, raised the intragastric pH above 6 within an hour. You can compare with the standard PPI, pantoprazole. In the first day of administration, more than 87% of 50mg tegoprazan group showed mean gastric pH more than 6. It was about 50% in the pantoprazole group. The second advantage is that tegoprazan is fast. As I mentioned earlier, PPIs are prodrugs requiring activation, but tegoprazan is an active drug, so it has a fast mode of action. In general, PPIs require a few days to reach their maximal effect. For example, the day 1 acid secretion curve after omeprazole medication is quite different from day 5. However, the day 1 and day 5 curve is almost the same for tegoprazan. It means tegoprazan shows its maximal effect with a single dose. We recently performed a clinical study comparing the night-time gastric acid supression of tegoprazan, vonoprazan and esomeprazole, The blue line is tegoprazan, the green line is vonoprazan and the orange line is esomeprazole. As you can see in the graph, tegoprazan rapidly raised gastric pH above 6 within an hour and it was maintained above 4 through the night. On the other hand, vonoprazan took 6 hours to reach pH 6. Esomeprazole was able to reach pH4 in 4 hours but showed relatively weak gastric acid suppression. In the clinical practice, tegoprazan is very effective for the control of the night-time breakthrough symptoms, this graph shows the reason why tegoprazan is more effective than vonoprazan and esomeprazole in the night-time GERD. Plasma half life of P-CAB is longer than that of PPIs. The plasma half life of tegoprazan is about 5 hours. This graph shows that the tissue tegoprazan concentration persists longer than the plasma concentration. After 8 hours of taking tegoprazan, the gastric radioactivity of tegoprazan was quite high in this animal model. And it is also known than the P-CABs are stable in the canaliculi of gastric parietal cells. This slide compares the pH profile of PPI and P-CAB. Tegoprazan shows maximal effect within an hour and the excellent acid suppression persists for quite a long time. Tegoprazan is a potent, fast, and long-acting acid blocker, which is useful in many different clinical situations. Tegoprazan is so potent that it is effective for severe reflux esophagitis, PPI-refractory GERD and Helicobacter pylori eradication. Tegoprazan is so fast that it is effective for the initial therapy of erosive erophagitis and NERD. Tepoprazan is so long-acting that it is effective for nocturnal symptoms and useful for the threshold therapy. From now on, I¡¯d like to review the safety issues of tegoprazan. Looking at database from 3.8 million people, the rate of adverse effects related to tegoprazan was very low. Hepatotoxicity was not a problem with tegoprazan. Hypergastrinemia is a common problem of all acid blockers. The level of hypergastrinemia was similar to lansoprazole and much lower than vonoprazan, a Japanese P-CAB. Because most PPIs are metabolized by cytochrome 2C19, they can inhibit the action of clopidogrel. Tegoprazan is mostly metabolized by cytochrome 3A4, so it has no significant drug drug interaction with clipodogrel. Tegoprazan is safely used in patients taking clipodogrel. We recently evaluated the pharmacokinetic characteristics of atorvastatin when co-administered with tegoprazan and vonoprazan. The black and white circles show the blood concentration of atorvastatin alone. The orange triangle is blood concentration of atorvastatin given with tegorazan. As you can see there is no atorvastatin concentration change with tegoprazan. The blue square is for vonoprazan. Vonoprazan slightly increased the atorvastatin concentration. We also evaluated the serum gastrin levels. As you can see, serum gastrin was significantly elevated after 7 days of vonoprazan. However, tegoprazan showed no such change. From now on, I¡¯d like to show you the clinical usefulness of tegoprazan in various situations. The first indication is erosive esophagitis. The initial effect of PPI takes about 3 days. The patient said that her symptom was gone completely 3 days after taking esomeprazole. But the effect of tegoprazan is much faster. In the afternoon, I gave tegoprazan to a 55 years old gentlemen, and I received a text message in the next morning. It said ¡°Thank you so much. I had a good night¡¯s sleep after taking tegoprazan.¡± OK. Tegoprazan is so fast and effective for controlling night time symptoms. Many patients are happy with tegoprazan. A patient said ¡°I am much better after taking tegoprazan. I am enjoying my meals.¡± What is the best choice for the initial treatment of GERD? We usually start with stronger medicine following the step down approach. Tegoprazan is stronger than double dose of PPI, so it is natural to start with tegoprazan than PPIs. In a recent review, professor Suzuki recommended to use P-CAB for the initial treatment of severe reflux esophagitis. In cases with mild erosive esophagitis or NERD, either P-CAB or PPI can be used. This is a recent guideline named Seoul Consensus for the diagnosis and management of GERD. It said ¡°The effect of P-CABs is comparable with that of PPIs for the initial treatment of patients with GERD.¡± The evidence was moderate and the recommendation was strong. With more publications, I think we can modify the statement in more favor of tegoprazan in the near future. Most experts strongly agreed with this statement. We need more data regarding the maintenance therapy of tegoprazan-responsive GERD. In a recent review, professor Suzuki recommended continuous P-CAB or continuous PPI for severe forms of erosive esophagitis. For milder forms of erosive esophagitis and NERD, he recommended on demand P-CAB. There is no on-demand PPI therapy in this figure. For the on-demand therapy, P-CAB is much more useful than PPI, because P-CAB is faster. The next topic is NERD. There is no head to head comparison study for NERD. A placebo controlled study was recently published by Korean researchers. As you can see in this slide, both tegoprazan 50mg and 100 mg were much better than placebo for the control of heartburn symptoms. In the subgroup analysis for severe heartburn symptom patients, the difference was more prominent. As expected, the effect of heartburn control was quite excellent on the first day of tegoprazan administration. Tegoprazan was so fast. I prescribed tegoprazan and in the next outpatient clinic the patient said ¡°the symptoms are gone in about 30 minutes and it is like nothing happened. Thank you.¡± Because of the time limitation, I will briefly touch up on refractory GERD. Going back to Professor Suzuki¡¯s algorithm, P-CAB is the only one option for PPI-resistant GERD. Tegoprazan is also useful for peptic ulcers. A gastric ulcer was found in a 78 year old woman with hypertension. / This is an image enhanced endoscopy named i-scan. / retroflexion / i-scan / biopsy/ Tegorazan was given. In the follow up endoscopy, the ulcer was completely healed. The trade name of tegoprazan is K-CAB in Korea and Åٽŧ in China. Ladies and gentlemen. I¡¯d like to wrap up my discussion by saying that tegoprazan is a potent, fast, and long-acting acid blocker, which is useful in many different clinical situations. Thank you very much for your attention.