Company: PHAT
Filing Date: 2025-03-06
Form Type: 10-K
Source: 0000950170-25-034183
Chunk: 37

Company: Phathom Pharmaceuticals, Inc.
Filing Date: 2025-03-06
Form: 10-K
Item: Item 1
Chunk 37
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 nausea, and gastroenteritis, reported at or below 5%.

In PHALCON-NERD-201, vonoprazan was generally well tolerated. In both phases of the trial, no adverse event was reported in more than three percent of the participants in a treatment group. There was a total of four SAEs in the daily dosing phase, only one of which was related to study drug, and no SAEs in the as needed phase. The safety data for all vonoprazan arms were comparable to placebo and consistent with what was reported in previous studies.

We also conducted a Phase 1, open-label study (VONO-401) to evaluate the pharmacokinetics, or PK, of vonoprazan in the breast milk of healthy lactating women following 20 mg once-daily or twice-daily regimens. The study enrolled women who had been breastfeeding or pumping for at least 4 weeks postpartum and temporarily discontinued breastfeeding during the treatment period. PK assessments demonstrated that the excretion of vonoprazan into breast milk was negligible, with less than 0.03% of the administered dose excreted and less than 0.3% of the weight-adjusted maternal dose potentially consumed by infants. Safety evaluations indicated that vonoprazan was well tolerated, with no significant safety concerns identified. These results suggest limited infant exposure to vonoprazan through breast milk.

Certain earlier generation PCABs previously under development by other companies may have been discontinued in-part due to their hepatic safety profile. These hepatic safety concerns may be compound-specific and not generalizable to the PCAB class. It is notable that vonoprazan is based on a pyrrole chemical structure and is chemically distinct from previously discontinued PCABs that were based on an imidazole structure. Vonoprazan has had a similar hepatic safety profile to lansoprazole across all clinical studies conducted by Takeda, in which 1.0% of subjects treated with vonoprazan 10 mg or 20 mg and 0.8% of subjects treated with lansoprazole 15 mg or 30 mg had alanine transaminase or ALT or aspartate transaminase or AST elevations greater than three times the upper limit of normal or bilirubin elevations greater than two times the upper limit of normal. Similarly, in the healing phase of PHALCON-EE, transient elevations in ALT or AST greater than