Company: PHAT
Filing Date: 2025-03-06
Form Type: 10-K
Source: 0000950170-25-034183
Chunk: 4

Company: Phathom Pharmaceuticals, Inc.
Filing Date: 2025-03-06
Form: 10-K
Item: Item 1
Chunk 4
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Vonoprazan has a differentiated mechanism of action from PPIs. Unlike PPIs, vonoprazan: 

•is stable in the presence of acid;

•does not require activation by gastric acid; 

•is designed to selectively concentrate in the parietal cells in both the resting and stimulated states, bind to the active pumps and remain associated with the active and inactive pumps;

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•can be taken independent from meal intake;

•binds to the pumps in a noncovalent and reversible manner; and  

•has a long plasma half-life that replenishes the drug at the site of action over the course of the day. 

These factors have enabled vonoprazan to demonstrate more rapid and potent acid suppression versus the PPIs esomeprazole and lansoprazole in human subjects two to three hours after oral dosing and maintain target acid inhibition over a 24-hour period in randomized, open-label, crossover clinical trials. In contrast, PPIs require three to five days to reach steady state acid suppression and do not reliably maintain target acid inhibition over a 24-hour period. In addition, vonoprazan demonstrated approximately 10-to-100-fold better acid control compared to lansoprazole and esomeprazole. 

Vonoprazan has demonstrated clinical advantages over the PPI lansoprazole in the treatment of Erosive GERD and H. pylori infection in completed Phase 3 clinical trials conducted in the United States and Europe, including:  

•more complete healing of Erosive GERD in patients with moderate to severe disease after two weeks; 

•more durable healing of Erosive GERD in patients with all grades of disease;

•higher H. pylori eradication rates in combination with antibiotics compared to standard of care triple therapy; and 

•more flexible dosing, including dosing independent of food and time of day.

Moreover, we believe that vonoprazan’s anti-secretory mechanism has the potential to contribute to additional clinical advantages over PPIs such as rapid symptom relief through "as- needed" dosing in the treatment of patients with Non-Erosive GERD.  

Erosive GERD. FDA approval of VOQUEZNA for the healing and maintenance of healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults was based on the results from PHALCON‑EE, our Phase 3 clinical trial conducted in