PROGRAMS

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Phathom Pharmaceuticals is developing vonoprazan, a potassium-competitive acid blocker (P-CAB). P-CABs are a novel therapeutic class with the potential to address multiple unmet needs among patients with gastroesophageal reflux disease (GERD) and other acid-related disorders.

The potassium-binding site of gastric hydrogen potassium ATPase (also known as the proton pump) is the enzyme primarily responsible for acidification of the stomach. Approximately 20% to 30% of patients are not well-controlled with PPIs which may be associated with slow onset of symptom relief, breakthrough heartburn, and treatment failure. These limitations are driven by the mechanism of action and pharmacologic profile of PPIs.

Vonoprazan has a novel mechanism of action and pharmacologic profile.

Vonoprazan: 

  • Binds to both active and inactive proton pumps with a slow dissociation rate

  • Does not require activation by gastric acid and has no food restriction

  • Is stable in the presence of gastric acid with prolonged retention in the gastric mucosa

  • Has a long plasma half-life

  • Is not primarily metabolized by CYP2C19

Vonoprazan is approved in multiple countries in Asia and Latin America for gastroesophageal reflux disease (GERD), including healing and maintenance of healing of erosive esophagitis, eradication of H. pylori infection, healing of gastric and duodenal ulcer, and prevention of recurrence of NSAID and low dose aspirin associated ulcer. Takeda and Otsuka co-promote vonoprazan in Japan, and Takeda markets vonoprazan in several additional Asian countries.

Phathom has development and commercialization rights to vonoprazan in the United States, Europe and Canada, and is advancing Phase 3 clinical development programs for the treatment of GERD and eradication of H. pylori.

Pipeline

Candidate Indication Discovery Phase 1 Phase 2 Phase 3
Vonoprazan Gastroesophageal Reflux Disease (GERD)
  • Erosive esophagitis (EE) healing
  • Maintenance of EE healing
  • EE heartburn relief

Phase 3

Vonoprazan in combination with antibiotics Helicobacter pylori infection

Phase 3

Candidate

Vonoprazan

Indication

Gastroesophageal Reflux Disease (GERD)
  • Erosive esophagitis (EE) healing
  • Maintenance of EE healing
  • EE heartburn relief

Phase 3

Candidate

Vonoprazan in combination with antibiotics

Indication

Helicobacter pylori infection

Phase 3

Gastroesophageal Reflux Disease (GERD)

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GERD is a condition in which reflux of gastric contents into the esophagus produces frequent or severe heartburn, regurgitation, and related symptoms. Over the long-term, GERD can result in inflammation and damage to the esophagus, pharynx, or respiratory tract and negatively affect quality of life. GERD is one of the most common diagnoses in the United States where approximately 45% of the population report symptoms at least once a month and 20% report symptoms at least once a week.

Phathom is developing vonoprazan for patients with erosive GERD, or erosive esophagitis (EE), a condition characterized by the presence of breaks, or erosions, in the esophageal tissue caused by constant irritation of the mucosal surface and subsequent loss of defense mechanisms against acid and digestive enzymes. Prolonged EE can lead to complications including peptic stricture, a narrowing of the esophagus that causes difficulty swallowing, and Barrett’s Esophagus (BE), a condition in which esophageal tissue changes can progress to cancer.

While PPIs can effectively treat many GERD patients, a substantial portion of patients do not respond to currently available PPIs. 15 to 40% of EE patients experience relapse despite chronic daily PPI maintenance therapy. Up to 40% of GERD patients without EE remain symptomatic on standard PPI therapy.   

 

Helicobacter pylori (H. pylori) Infection

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Approximately 30% of the US population is colonized in the gut by H. pylori, a bacterial pathogen associated with a wide range of upper gastrointestinal diseases including gastritis, peptic ulcer, and gastric cancer. Antibiotics used to treat H. pylori lose effectiveness as the stomach environment becomes more acidic.  Therefore, PPIs are commonly used as adjunctive therapy to raise pH and enhanced bactericidal activity.  However, as H. pylori resistance to commonly used antibiotics has increased, the effectiveness of standard antibiotic and PPI-based regimens has decreased to less than 80% in many regions. A significant unmet need has emerged for an anti-secretory agent to provide greater acid suppression and therefore restore the activity of antibiotics for the eradication of H. pylori.