Peptide education
PN-943
PN-943 is an investigational oral peptide designed to block the alpha4beta7 integrin, a target involved in immune-cell movement into the intestine. It was studied in adults with moderate to severe ulcerative colitis.
IDEAL, the phase 2 PN-943 study, missed its prespecified high-dose remission endpoint. A lower-dose group showed a numerical signal, but its remission comparison did not reach conventional statistical significance.
Overview
Quick answer
PN-943 and PTG-100 are different investigational candidates. PTG-100 was developed earlier; results from its studies are not PN-943 results.
What is PN-943?
It is a peptide developed as an oral antagonist of alpha4beta7 integrin. The target is involved in directing immune cells toward intestinal tissue.
What happened in the main trial?
IDEAL compared 450 mg twice daily, 150 mg twice daily, and placebo. Its prespecified primary comparison tested clinical remission with 450 mg versus placebo after 12 weeks and did not meet the endpoint.
What about the lower dose?
The conference abstract reported remission in 14 of 51 participants (27.5%) in the 150 mg group versus 8 of 55 (14.5%) with placebo. The secondary comparison had a nominal p value of 0.081. The abstract described a one-sided 5% significance threshold, and this comparison alone does not establish efficacy.
Is PTG-100 another name for PN-943?
No. The developer described PTG-100 as an earlier candidate replaced by PN-943. Their shared target does not make their clinical results interchangeable.
Evidence
Evidence snapshot
Reported remission at week 12 was 8 of 53 (15.1%) with 450 mg twice daily and 8 of 55 (14.5%) with placebo in the modified analysis.
The 150 mg group had remission in 14 of 51 participants (27.5%) versus 8 of 55 (14.5%) with placebo, with a nominal p value of 0.081. The abstract described a one-sided 5% threshold.
The induction results are available in a conference abstract and sponsor presentation. The completed trial registry did not include posted results.
In its annual filing, the developer said it did not intend to devote further internal resources to clinical development of PN-943.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| PN-943 achieved its main phase 2 goal. | The prespecified primary test was remission at week 12 for 450 mg twice daily versus placebo. The reported rates were 15.1% and 14.5%. | The comparison did not meet the primary endpoint. |
| The lower-dose result proves the drug works. | The 150 mg group had a higher numerical remission rate than placebo, but the reported nominal p value was 0.081. The abstract also reports other secondary measurements. | The lower-dose findings warrant cautious interpretation and confirmation; they do not turn the missed primary endpoint into a positive trial. |
| PN-943 and PTG-100 are the same peptide. | The developer identified PTG-100 as a prior candidate and PN-943 as its replacement for further development. | They are separate candidates. PTG-100 trial results should not be labeled as PN-943 results. |
Bottom line
Main takeaway
PN-943 was tested for ulcerative colitis, but the main study comparison did not establish a benefit over placebo.
The lower-dose remission rate was numerically higher, but the comparison was secondary and did not cross the abstract's stated one-sided 5% significance threshold.
The available induction data come from an investigator conference abstract and sponsor presentation, with no results posted in the trial registry.
Identity
What it is
PN-943 was designed as an oral, gut-targeted peptide antagonist of alpha4beta7 integrin. The IDEAL study enrolled adults with active moderate to severe ulcerative colitis.
PTG-100 is a distinct earlier candidate in the same target class. A trial of PTG-100 does not measure the effects or safety of PN-943.
Use context
Routes, doses, and cycle patterns
The IDEAL study compared two oral PN-943 regimens with placebo during a 12-week induction period, followed by an extended treatment period for eligible participants.
Human studies and product labels
IDEAL primary comparison
- Context
- Adults with moderate to severe ulcerative colitis
- Route
- Oral
- Amount
- 450 mg
- Frequency
- Twice daily
- Duration
- 12-week placebo-controlled induction
The prespecified clinical-remission comparison against placebo did not meet its endpoint.
IDEAL lower-dose comparison
- Context
- Same randomized induction study
- Route
- Oral
- Amount
- 150 mg
- Frequency
- Twice daily
- Duration
- 12-week placebo-controlled induction
Remission was 14 of 51 (27.5%) versus 8 of 55 (14.5%) on placebo in the reported modified analysis; the nominal p value was 0.081. The abstract described a one-sided 5% significance threshold.
Research
Research evidence
IDEAL randomized 169 adults. The reported modified analysis included 159 participants and did not show a primary-endpoint benefit at 450 mg twice daily. The lower-dose remission comparison was numerical and secondary.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| IDEAL phase 2 induction | 169 randomized adults with moderate to severe active ulcerative colitis | Randomized, double-blind, placebo-controlled study | Oral PN-943 450 mg or 150 mg twice daily for 12 weeks | In the reported modified analysis, remission was 8 of 53 (15.1%) for 450 mg versus 8 of 55 (14.5%) for placebo. At 150 mg it was 14 of 51 (27.5%), with nominal p = 0.081 versus placebo. | The primary endpoint tested 450 mg, not 150 mg. The reported induction results are an abstract and sponsor presentation rather than a full trial report, and the registry did not include posted results. The abstract described a one-sided 5% threshold and nominal secondary comparisons. | Limited human evidence from a randomized study |
| PN-943 development filing | PN-943 clinical program | Sponsor annual filing and completed trial registration | Investigational candidate | The sponsor reported phase 2 completion and no intention to dedicate further internal resources to its PN-943 clinical program. | A sponsor's plans may change. The statement is not a later efficacy result. | Development-status evidence |
Cautions
Safety and unknowns
- The conference abstract reported no drug-related serious adverse events or discontinuations during induction. The trial was too small to rule out rare harms, and the abstract does not establish long-term safety.
- Ulcerative colitis outcomes depend on disease activity and treatment context. The phase 2 result does not establish safety or efficacy in other inflammatory conditions.
- The registered oral trial formulation and monitoring do not establish the composition or safety of other products using the PN-943 name.
Mechanism
How it is proposed to work
PN-943 targets alpha4beta7, an integrin involved in immune-cell traffic to intestinal tissue. The intended effect is to reduce inflammatory cell recruitment in ulcerative colitis.
The IDEAL investigators measured peripheral target occupancy as well as clinical outcomes. Evidence of target engagement is not the same as a demonstrated clinical-remission benefit.
PTG-100 also targets alpha4beta7, but it is a different candidate whose human study findings cannot be assigned to PN-943.
Details
Technical details
Sources
References
- 1.
ClinicalTrials.gov. PN-943 phase 2 IDEAL trial registry
NCT04504383
Registry records the design, treatment groups, and completed study status; results are not posted.
- 2.
Other. IDEAL phase 2 PN-943 trial: investigator conference abstract
doi:10.1002/ueg2.12293
Conference abstract OP088 reports the induction analysis; it is not a full trial report.
- 3.
Other. PN-943 IDEAL trial sponsor results presentation
Sponsor presentation reports the prespecified endpoint and lower-dose analysis.
- 4.
Other. PN-943 development status in sponsor annual filing
Sponsor reports phase 2 completion and no planned further internal clinical-development resources.
- 5.
Other. Sponsor filing distinguishing PN-943 from PTG-100
The developer identifies PTG-100 as an earlier candidate replaced by PN-943.