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
"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
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.
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.
About
Protagonist is headquartered in
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding our intentions or current expectations concerning, among other things, the availability of results of our clinical trials. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreement with Janssen, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the
SOURCE
Solebury Trout, Rich Allan (media), Tel: +1 646-378-2958, Email: rallan@soleburytrout.com, OR Marcy Nanus (investors), Tel: +1 646-378-2927, Email: mnanus@soleburytrout.com