Oral Alpha-4-Beta-7 Integrin Antagonist PN-943 Demonstrates Sustained Dose-Related Target Engagement Activity in a Multiple Ascending Dose Phase 1 Study
"These dose-finding results from the multiple ascending dose (MAD) part of the Phase 1 study with two weeks of daily administration of PN-943 are consistent with the previously reported preclinical and Phase 1 single ascending dose (SAD) data with PN-943," commented
PN-943 has been designed as a second generation oral, gut-restricted, alpha-4-beta-7-integrin antagonist with superior potency in comparison to the previous candidate PTG-100 that has validated this novel approach based on our findings from the Phase 2 PROPEL trial in patients with ulcerative colitis (UC) with PTG-100. In the MAD part of the Phase 1 study, PN-943 was administered daily over 14 days. The new results from the MAD part of the study are briefly described below and a complete presentation of the Phase 1 study results is scheduled for the
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) on day 14 in alpha-4-beta-7 positive CD4 positive memory T cells is provided below (mean ± standard deviation).
Dose (mg) |
PN-943 %RO (max) (n=8) |
PTG-100 %RO* (max) (n=8) |
PN-943 %RO (AUC0-24) (n=8) |
PTG-100 %RO* (AUC0-24) (n=8) |
100 mg |
56 ± 8.8 |
26 ± 9.8 |
971 ± 179 |
384 ± 180 |
300 mg |
80 ± 5.4 |
51 ± 7.0 |
1467 ± 145 |
930 ± 226 |
1000 mg |
96 ± 1.0 |
74 ± 6.9# |
1957 ± 372 |
1544 ± 144# |
*Previously reported results from Phase 1 trial of PTG-100 in healthy volunteers (table above). |
# N=7 |
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.
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SOURCE
Solebury Trout, Rich Allan (media), Tel: +1 646-378-2958, Email: rallan@soleburytrout.com OR Brian Korb (investors), Tel: +1 646-378-2923, Email: bkorb@soleburytrout.com