Thank you for your kind introduction, Mr. chairman. My name is Jun Haeng Lee from Samsung Medical Center, Seoul Korea. I¡¯d like to start off by saying thank you for the invitation to this important luncheon seminar. K-CAP, tegoprazan is the most commonly prescribed acid blocking agent in Korea, so most doctors in this hall already knows this medicine quite well. After a brief review on tegoprazan, I¡¯d like to discuss some cases of gastroesophageal reflux disease and peptic ulcers. Tegoprazan is a kind of P-CAB, potassium competitive acid blocker, which was developed in Korea. It was launched under the name of K-CAB on March 1st 2019. The standard dose in 50mg. It has been approved for 5 indications, ERD, NERD, gastric ulcer, Helicobacter pylori eradication and maintenance therapy. With the development of potassium competitive acid blockers, such as tegoprazan, the treatment strategy of gastroesophageal reflux disease has dramatically changed in daily practice. In the recently published GERD guideline named 2020 Seoul Consensus, statement 21 says the efficacy of potassium-competitive acid blocker is comparable to proton pump inhibitors, hence they are recommended as an initial treatment of gastroesophageal reflux disease. The level of recommendation was strong. Two third of experts agreed strongly with this statement. P-CAB differs from PPIs in terms of mode of action. PPIs irreversibly bind to the proton pumps and inhibit acid secretion. On the other hand, P-CABs block the K+ exchange channel resulting in reversible inhibition of acid secretion PPIs are a pro-drug, which means they should be activated when it meets acid in the stomach. However, their critical limitation is that it only binds to active proton pumps which results in slow onset time. In addition, the half-life of PPIs are only 1 to 2 hours and is vulnerable in an acidic environment which prevents it from lasting in the lumen and binding to newly activated proton pumps. On the other hand, tegoprazan itself is a active drug. Not only does it bind to active proton pumps, it binds to proton pumps that are in resting state. Tegoprazan¡¯s half-life is 4 to 5 hours long and is strong in an acidic environment which enables it to last in the lumen and bind to newly activated proton lumps. These properties of tegoprazan enables fast and potent inhibiton of gastric acid secretion. Once again, this is the key differences between PPI and tegoprazan. Reversible binding, stable in the acidic environment, active drug, and long half-life. Because of theses differences, tegoprazan is a novel, fast, and potent acid blocker. It¡¯s maximal efficacy can be reached within one day, actually a few hours. From now on, I¡¯d like to explain tegoprazan¡¯s first strength. Tegoprazan is fast. As you can see on the graph, tegoprazan enables the stomach to reach pH4 within 1 hour, which is faster than the other drugs such as esomeprazole and vonoprazan. Because of these characteristics, typical symptoms of GERD such as heartburn and acid regurgitation can be relieved very quickly after the first medication. So tegoprazan is very useful for the initial symptom control and on-demand maintenance treatment. Tegoprazan is fast. Tegoprazan shows good efficacy on the first day of administration. As you can see on the graph, there is little difference in efficacy on the first day and two weeks of tegoprazan treatment. In comparison, PPI takes 5 days to reach its maximal efficacy. This is a case of a 50 years old male who took PPIs due to GERD. A few months after discontinuing PPI treatment, he experienced sudden heartburn symptoms. He is a medical doctor, and I recommended to try tegoprazan. He took tegoprazan late in the afternoon and I recieved the following message next morning. It was seven o¡¯clock. It says he had a good night¡¯s sleep after taking just on tablet tegoprazan. I¡¯ve never got a message like this with H2 receptor antagonist or PPI. As I already mentioned, PPI takes several days to achieve symptomatic relief but tegoprazan acts almost immediately. Tegoprazan is really fast. Tegoprazan showed faster night-time acid breakthrough control compared to esomeprazole. The effectiveness and safety of tegoprazan in erosive reflux disease patients with night-time heartburn and sleep loss was evaluation in this trial. It took 1.5 days to achieve the patient¡¯s first nocturnal acid breakthrough-free night while esomeprazle took 3 days. Tegoprazan is very useful in the symptom management of erosive reflux disease. But it is also useful for the treatment of non-erosive reflux disease. As you can see in this figure, tegoprazan showed fast heartburn relief in patients with moderate to severe non-erosive reflux disease patients from the 1st day. In one week, it reached 65 percent. Tegoprazan in good night-time acid control. It is well-known that nocturnal acid breakthrough occurs despite PPI treatment. Tegoprazan showed sustained acid control for most part of the day including night-time acid control. This is the comparison with dexlansoprazole. Tegoprazan was superior to dexlansoprazole in terms of median PH and percent time above pH 4. Although there was no statistical significance, tegoprazan inhibited nocturnal acid secretion slightly longer than vonoprazan. However, tegoprazan showed significantly longer night-time acid inhibition compared to esomeprazole. There is no food effect. PPIs are pro-drugs that can only be effective upon activation through gastric acid. PPIs should be taken 1 hour before a meal in order to be effective, making compliance problem. Tegoprazan can be taken regardless of food intake. The PK profile for Tegoprazan was similar when taken 30 minutes before a meal and fasting state. The intragastric pH in terms of percent time above 4 and median pH was similar when administered in fasting state, 30 minutes before a meal and 30 minutes after a meal. Tegoprazn can be used for Helicobacter eradication. Tegoprazan provides optimal gastric acid levels for H. pylori eradication. With twice a day treatment, tegoprazan¡¯s mean % time pH>6 was significantly higher than Pantoprazole. The eradication rate of 2 week tegoprazan-based triple therapy was 78% in ITT analysis, and 85% in PP analysis. Tegoprazan has low DDI potential. It is well known that there are variations in CYP2C19, especially in the Asian population. As you can see in the graph, the PPI efficacy differs greatly depending on the cytochrome 2C19. In this study the effect of tegoprazan was not different in terms of CYP2C19 phenotype. It is because tegoprazan is mostly metabolized by CYP3A4. There is a concern about the cytochrome 3A4. For example, atorvastatin is metabolized by cytochrome 3A4. When atorvastatin was given with vonoprazan, the level of atorvastatin and atorvastatin lactone were significantly increased. However, with tegoprazan, atorvastatin, 2-hydroxyatorvastatin, atorvastatin lactone were similar. I am sorry for the busy slide, but the message is that tegoprazan has low drug-drug interaction with NSAIDs. Tegoprazan formulation is simple. Tegoprazan has three formulation. 50 mg, 25 mg, and orally disintegrating tablet. Because of tegoprazan is strong in acidic environment, no enteric coating is required. I will briefly show you some of the clinical study results with my personal cases. In the healing rate of erosive esophagitis, tegoprazan is non-inferior to esomeprazole. A 49 year old Caucasian male patient visited international clinic with heartburn symptoms. A Korean American doctor performed the endoscopy. There were multiple longitudinal mucosal breaks with sliding type hiatal hernia. The mucosal breaks showed confluent lesions at the far distal esophagus. Multiple biopsies were done at distal esophagus. The biopsy result was surprising ? high grade squamous dysplasia. What would you do with this a little bit tricky pathology results. I call it tricky because dysplasia is difficult to evaluated in the setting of severe inflammation. The cells looked dysplastic but a definity invasion was not observed. Do you think it is a true neoplasia or only the result of inflammation. 4 weeks of Tegoprazan was given and a follow up endoscopy was done. All the mucosal breaks in the previous endoscopy were completely disappeared. Sliding type hiatal hernias is the same, but squamo-columnar junction is very clear now. This case shows the speed of mucosal break healing by tegoprazan treatment. As you can see, the dysplastic changes were almost disappeared in the forceps biopsy specimen. The biopsy results were reported as acanthotic squamous epithelium You can clearly see the difference between the upper and lower pictures. Before and after tegoprazan treatment for 4 weeks. The mucosal break healing is really fast. In the symptom relief of the nonerosive reflux disease, tegoprazan was significantly superior to the placebo. The effect on NERD was shown from the first day of tegoprazan treatment. A 76 year old male farmer visited my clinic due to acid regurgitation. In the endoscopy, no mucosal break was found, but a short segment hiatal hernia was found. His symptom, acid regurgitation, was aggravated in the bending over position during his work at the farm. My choice was tegoprazan 50mg daily for a couple of weeks. Four weeks later at my outpatient clinic, he was very happy with tegoprazan. He said that the medicine, tegoprazan, worked very well for him, and he has no symptom now. Very good. I recommended to use the same medicine, tegoprazan on-demand in the future. The Helicobacter eradication rate was 69% for tegoprazan and 67% for lansoprazole. Maybe, higher dose should be tested. In the healing rate of gastric ulcer, both tegoprazan and lansoprazole were excellent. This is a case with benign gastric ulcer. An active ulcer crater with surrounding edema was found in a 78 years old woman with hypertension. The biopsy was Helicobacter-associated gastritis, and there was no evidence of malignancy. Following the Korean guideline, 2 weeks of Helicobacter eradication treatment was done. And then, tegoprazan was given for 8 weeks. As you can see in the follow up endoscopy 2 months later, the ulcer crater has disappeared. In the long-term maintenance therapy for erosive esophagitis, tegoprazan half dose was not inferior to lansoprazole half dose. In the subgroup analysis for severe reflux esophagitis, such as LA B, C and D, tegoprazan half dose was superior to lansoprazole half dose. The effect in the maintenance treatment was not different by the dcytochrome 2C19 phenotypes. Safety data. Of all the reported ADRs reported in Korean Tegoprazan clincial trials, none were related to hepatotoxicy Serum gastrin levels were similar between tegoprazan 100mg and lansoprazole 30mg and significantly lower in tegoprazan 50mg. In the half dose tegoprazan long-term treatment, gastrin, pepsinogen 1, and did not change. There was no significant rise in level of gastrin after tegoprazan administration After 6 months of half doe tegoprazan 25mg treatment, no deficiencies such as vitamin B12 and iron malabsorption, no hypomagnesemia was observed A small fundic gland polyp can develop after long-term treatment with PPI of PCAB. Observation without polypectomy is usually recommended. However, some patients may want to remove it. In that case, a small polypectomy can be done in the outpatient setting. Some more cases. A 69 years old lady was referred due to recent onset indigestion, mild swallowing difficulty, belching and dry coughing. In the endoscopy at local clinic, the EG junction was a little bit narrowed by severe mucosal swelling at the far distal esophagus. No definite ulcer was found in the endoscopic images. What would you do at this situation? Would you do the endoscopy immediately or a few days later after a short course of medication. For me, it did not look like a cancer, so I decided to do endoscopy 2 weeks after a short course of tegoprazan medication. OK. This is the follow up endoscopy 2 weeks after tegoprazan medication. The mucosal edema at the GE junction had disappeared, and clear observation of the distal esophagus was possible. In the picture at the left-hand side, you can see a sliding type hiatal hernia, and the esophageal mucosa looked a little bit white and less transparent, which are secondary findings of squamous epithelial hyperplasia due to reflux disease. In the picture at the right-hand side, there was a small triangular shaped mucosal break just above the squamocolumnar junction. The next case is a 64 years old female patient. In the screening endoscopy with Pentax, a small depressed lesion with a bright red nodule at the corner was found at the gastric angle. The ill-defined surrounding mucosa was hyperemic and irregular. The biopsy was not conclusive. It said tubular adenoma with high grade dysplasia versus tubular adenocarcinoma well differentiated. What¡¯s your opinion? Considering the gross morphology and the biopsy result, it should be an early gastric cancer 2c type. I did an endoscopic submucosal dissection with Olympus. The depressed lesion was already healed. Maybe she took some kind of medicine after the screening endoscopy. / The border of the lesion was unclear / even after image enhanced endoscopy, NBI. / After spraying indigo carmine, the border became much clear. Marking and injection was done as usual / and circumferential cutting was done with Fujifilm F knife. / Submucosal dissection was done with Olympus IT-2 knife. / There was no complication. This is the ESD pathology. It was 36mm-sized well differentiated tubular adenocarcinoma. Depth of invasion was muscularis mucosa, and lateral margin and deep margin was all negative. There was no lymphovascular invasion. So, the conclusion was pathological curative resection. There was no evidence of recurrence during the follow up period. But, typical reflux symptoms, such as heartburn and acid regurgitation, developed recently. Ladies and gentlemen, what¡¯s your treatment of choice for recent onset reflux symptoms. My choice was tegoprazan as usual. Two weeks later, the patient was very happy at my out-patient clinic. She said ¡°I think I have recovered to about 80% of my normal state.¡± I recommended the threshold therapy. Take tegoprazan every other day. If the symptom is OK, take tegoprazan twice a week. And then, you can try on-demand therapy. A 56 years old gentleman visited my clinic with heartburn symptoms and a small sentinel polyp at his squamocolumnar junction. I recommended tegoprazan on demand therapy. This is the follow up endoscopy 1 year later. As you can see, the sentinel polyp just disappeared. Very good. Recently, he¡¯s taking tegograzan once a week. Ladies and gentlemen, I¡¯d like to wrap up my luncheon seminar by saying that Tegoprazan, the new Korean P-CAB, was approved in 2018 in South Korea for the treatment of erosive esophagitis (EE) and non-reflux erosive disease (NERD). Currently, it has also been approved for the treatment of gastric ulcer and eradication of H. pylori. Tegoprazan is a fast, potent and safe acid blocker. It can reach intragastric pH 4 within 1 hour, has bioavailability that is not limited by food intake, may improve control of NAB, has low DDI potential with clinical drugs metabolized by CYP, and has low risk of hypergastrinemia. Thank you for your attention.