Oral Alpha-4-Beta-7 Integrin Antagonist PN-943 Demonstrates Superior Dose-Related Target Engagement Activity to PTG-100 in Single Ascending Dose Phase 1 Study

-- PN-943 was safe and well tolerated with gut-restricted exposure --

-- Pharmacodynamic data for PN-943 in healthy volunteers confirm higher potency observed in preclinical studies versus PTG-100 --

NEWARK, CA, USA I May 14, 2019 I Protagonist Therapeutics, Inc. (Nasdaq:PTGX) today announced results from the initial single ascending dose (SAD) part of the Phase 1 study of PN-943, an oral, gut-restricted alpha-4-beta-7 integrin specific antagonist in development for the potential treatment of inflammatory bowel disease (IBD). Results of the first clinical study of PN-943 in a randomized, double-blind, placebo-controlled, dose escalation study in healthy volunteers demonstrated that administration of PN-943 was safe and well tolerated, with no reported serious adverse events. The pharmacokinetic and pharmacodynamic parameters were consistent with the design of PN-943 as a gastrointestinal-restricted alpha-4-beta-7 integrin antagonist. 

"These dose-finding results are consistent with the preclinical properties of PN-943, including superior target engagement as compared with prior compound PTG-100," commented Samuel Saks, M.D., Protagonist Chief Medical Officer. "PN-943 has been designed with superior potency and a longer half-life of dissociation. In addition, PN-943 applies the oral, gut-restricted, integrin antagonist approach that has been validated by previous studies in ulcerative colitis (UC) patients with PTG-100."

As previously announced, PN-943 replaced PTG-100 as a candidate for the treatment of IBD and demonstrated higher potency to PTG-100 in all preclinical studies. These preclinical results are supported by the results of the SAD part of the Phase 1 study. Results from the multiple ascending dose (MAD) part of the Phase 1 study are expected in the third quarter of 2019. Cumulative SAD and MAD data from the PN-943 Phase 1 are intended to be used to design a Phase 2 UC study with PN-943.

A summary of results of target engagement as measured by maximum blood receptor occupancy (%RO) and 24 hour area under the %RO curve (AUC0-24) in alpha-4-beta-7 positive CD4 positive memory T cells are provided below (mean ± standard deviation). Detailed results from the Phase 1 study are expected to be presented at an upcoming medical conference.

Dose (mg)

PN-943 %RO

(max)

PTG-100 %RO*

(max)

PN-943 %RO

(AUC0-24)

PTG-100 %RO*

(AUC0-24)

100 mg (n=8) 62 ± 11.0 29 ± 7.7 933 ± 299 470 ± 195
300 mg (n=8) 83 ± 7.9 54 ± 10.0 1542 ± 158 746 ± 199
1000 mg (n=8) 94 ± 2.0 74 ± 9.7 1944 ± 84 1351 ± 186
1400 mg (n=8) 95 ± 3.6 N/A 2064 ± 164 N/A

*Previously reported results from Phase 1 trial of PTG-100 in healthy volunteers (table above).
The Phase 2 PROPEL trial of PTG-100 in patients with ulcerative colitis has previously demonstrated that pharmacodynamic responses correlate with histologic remission and clinical efficacy responses (see Sandborn, W. et al., PTG-100, an oral gut-restricted peptide alpha-4-beta-7 antagonist, induces clinical and histologic remission in patients with moderate to severely active ulcerative colitis. United European Gastroenterology Journal 2018; 6 (Supplement 1), 2018)

About PN-943

PN-943 is an oral, gut-restricted alpha-4-beta-7 integrin specific antagonist peptide in clinical development for the treatment of inflammatory bowel disease. PN-943 is designed to offer the convenience of oral administration and the potential for improved safety and tolerability compared to antibody therapeutics administered by injection that target the alpha-4-beta-7 integrin pathway. Protagonist Therapeutics is currently evaluating PN-943 in a randomized, double-blind, placebo-controlled, dose escalation (100, 300, 1000 and 1400 mg) Phase 1 study in normal healthy volunteers.

About Protagonist Therapeutics, Inc.

Protagonist Therapeutics is a clinical stage biopharmaceutical company that utilizes a proprietary technology platform to discover and develop novel peptide-based drugs to transform existing treatment paradigms for patients with significant unmet medical needs. PTG-300 is an injectable hepcidin mimetic for the potential treatment of anemia and iron overload related rare blood diseases with an initial focus on beta-thalassemia. PTG-200 is an oral, gut-restricted interleukin-23 receptor antagonist in development for the treatment of inflammatory bowel disease. The Company has a worldwide license and collaboration agreement with Janssen Biotech for the clinical development of PTG-200. PN-943 is an oral, gut-restricted alpha-4-beta-7 integrin antagonist peptide in development for the treatment of inflammatory bowel disease.

Protagonist is headquartered in Newark, California, with pre-clinical and clinical staff in California and discovery operations in both California and Brisbane, Queensland, Australia. For further information, please visit http://www.protagonist-inc.com

SOURCE: Protagonist Therapeutics

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