PN-943 / Protagonist Therap - LARVOL DELTA

Protagonist Reports First Quarter 2023 Financial Results and Provides Corporate Update (PRNewswire) - "Research and Development ('R&D') Expenses: R&D expenses for the first quarter of 2023 were $27.4 million, as compared to $36.3 million for the first quarter of 2022. The decrease in R&D expenses from prior year quarter was primarily due to decreases in PN-943 expenses and costs related to the completion of JNJ-2113 and PN-232 Phase 1 trials, partially offset by an increase in rusfertide expenses related primarily to the Phase 3 VERIFY clinical trial. We do not intend to dedicate further internal resources to clinical development or contract manufacturing activities for our PN-943 clinical program."

Commercial • Immunology • Inflammatory Bowel Disease • Psoriasis • Ulcerative Colitis

PN-943 in Adults With Moderate to Severe Active Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=169 | Completed | Sponsor: Protagonist Therapeutics, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jun 2023 ➔ Feb 2023 | Trial primary completion date: Jun 2022 ➔ Feb 2023

Trial completion • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist Reports Third Quarter 2022 Financial Results and Provides Corporate Update (PRNewswire) - "PN-943: Oral, Gut-Restricted, alpha-4-beta-7 Integrin Antagonist for Ulcerative Colitis (UC); With the exception of completing the 40-week extended treatment period for eligible patients in the Phase 2 IDEAL study, expected to be completed in Q1 2023, the Company intends to dedicate no further internal resources to clinical development or CMC activities for PN-943....Research and Development ('R&D') Expenses: R&D expenses were $25.4 million and $96.3 million for the three and nine months ended September 30, 2022 as compared to $37.0 million and $87.6 million for the same periods in 2021. The decrease in R&D expense from prior year quarter was primarily due to lower PN-943 expenses related to the suspension of further program expenditures..."

Commercial • Trial completion date • Inflammatory Bowel Disease • Ulcerative Colitis

A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF THE ORAL, GUT-RESTRICTED Α4Β7 INTEGRIN PEPTIDE ANTAGONIST PN-943 IN PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS: RESULTS FROM THE IDEAL STUDY (UEGW 2022) - "PN-943 has ~3 times more potency than the first-generation candidate PTG-100 which demonstrated signs of clinical efficacy in a phase 2 ulcerative colitis (UC) study (Gastroenterol 2021; 161:1853-1864)...Key inclusion criteria were moderate to severe UC defined as a 3-component Mayo score (Stool Frequency Score (SFS), Rectal Bleeding Score (RBS), and centrally read Mayo Endoscopic Subscore (MES)), of 5-9; and prior inadequate response/intolerance to at least 1 conventional therapy, or a maximum of one biologic (excluding vedolizumab).  PN-943 at 150 mg BID, but not 450 mg BID, demonstrated concordant treatment effects across multiple secondary endpoints with nominal statistically significant differences in histologic remission/improvement and endoscopic improvement. These results suggest a novel mechanism of action for PN-943 affecting α4β7-MADCAM interactions in the local GI tissue environment and support further development of PN-943 in registrational UC trials."

Clinical • P2 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist Reports Second Quarter 2022 Financial Results and Provides Corporate Update (PRNewswire) - "The Company submitted a request to FDA for a clinical protocol guidance meeting and is awaiting written responses from FDA related to the Phase 3 study plan. The Phase 3 study plan is anchored around the 150 mg BID dose of PN-943, pending regulatory guidance. Protagonist intends to pursue further clinical development of PN-943 in collaboration with a large pharmaceutical partner. As announced previously, the Company has engaged PJT Partners to identify and evaluate such partnering opportunities. The results of the IDEAL study have been selected for an oral presentation at the United European Gastroenterology Week (UEGW) in October 2022....R&D expenses were $34.6 million and $70.9 million for the three and six months ended June 30, 2022 as compared to $26.4 million and $50.7 million for the same periods in 2021. The increases were primarily due to costs associated with advancing rusfertide and PN-943, including current and planned Phase 3 clinical trials."

Commercial • FDA event • Licensing / partnership • Inflammatory Bowel Disease • Ulcerative Colitis

THE IDEAL STUDY: A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTI-CENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF THE ORAL α4β7 INTEGRIN PEPTIDE ANTAGONIST PN-943 IN PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS (DDW 2022) - "PN-943, a second generation oral α4β7 peptide antagonist with approximately 3 times more in vitro and in vivo potency than PTG-100, has demonstrated dose dependent blood α4β7 receptor occupancy, as well as reduction in receptor expression in a phase 1 study in healthy volunteers (Clin Pharmacol Drug Dev...Key inclusion criteria are moderate to severe UC defined as an adapted 3-component Mayo score, comprised of Stool Frequency Score (SFS), Rectal Bleeding Score (RBS), and Mayo Endoscopic Subscore (MES), of 5-9; and prior inadequate response, loss of response, or intolerance of at least 1 of oral aminosalicylates, corticosteroids, immunosuppressives, or a biologic (excluding vedolizumab)...We will present key efficacy and safety analyses from the primary week 12 endpoint. The data will help elucidate the utility of a highly potent oral, peptide α4β7 inhibitor in UC."

Clinical • P2 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist Reports First Quarter 2022 Financial Results and Provides Corporate Update (PRNewswire) - "Research and Development ('R&D') Expenses: R&D expenses for the first quarter of 2022 were $36.3 million as compared to $24.2 million for the same period of 2021. The increase was primarily due to costs associated with advancing our pipeline assets rusfertide and PN-943, including current and planned Phase 3 clinical trials."

Commercial • Inflammatory Bowel Disease • Ulcerative Colitis

Phase 2 Data Positive for PN-943 as an Ulcerative Colitis Treatment (HCPLive) - '"The oral, gut-restricted agent PN-943 appears to exert similar effects at the twice daily 150 mg dose in comparison to the approved injectable alpha-4-beta-7-integrin antibody drug and its mechanism of action," said Bruce Sands, MD, MS...'There is a clear unmet need and strong clinical benefit for patients with an oral agent working through such a proven IBD specific mechanism, and the IDEAL study results provide good rationale for moving PN-943 forward in a Phase 3 registrational study.'"

Media quote

Protagonist Therapeutics Announces Topline Data from Phase 2 IDEAL Study of PN-943 in Ulcerative Colitis (PRNewswire) - P2 | N=150 | IDEAL (NCT04504383) | Sponsor: Protagonist Therapeutics, Inc. | "PN-943 achieved 27.5% clinical remission with a delta of 13% versus placebo, with strong concordance across all key proxies including histological and endoscopic endpoints for efficacy, in the twice daily 150 mg dose arm; Achieved clinical proof-of-concept and validation for oral, gut-restricted approach for ulcerative colitis via blockade of the alpha-4-beta-7-integrin pathway; Protagonist Therapeutics...announced topline results from the Phase 2 IDEAL study evaluating PN-943 in patients with moderate-to-severe ulcerative colitis (UC)."

P2 data • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist (PTGX) receives letter from FDA indicating intent to rescind Breakthrough Therapy Designation of rusfertide product candidate in polycythemia vera (Streetinsider.com) - "Protagonist Therapeutics, Inc...expects to announce top-line data from its Phase 2 clinical trial evaluating its product candidate PN-943 for ulcerative colitis in the first half of the second quarter of 2022."

P2 data • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Corporate Update (PRNewswire) - "Topline results from the Phase 2 IDEAL study of PN-943 in ulcerative colitis expected in Q2 2022...PN-235 is also expected to advance into Phase 2 clinical studies in inflammatory bowel diseases in 2H 2022....Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents and marketable securities as of December 31, 2021 were $326.9 million....Our cash forecast will be updated following the PN-943 Phase 2 study UC data readout in the second quarter of 2022...Research and Development ('R&D') Expenses: R&D expenses for the fourth quarter and full year 2021 were $38.4 million and $126.0 million respectively...The increases in 2021 were primarily due to the additional costs associated with advancing rusfertide and PN-943 through Phase 2 studies..."

Commercial • New P2 trial • P2 data • Immunology • Ulcerative Colitis

PN-943 in Adults With Moderate to Severe Active Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Protagonist Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist Therapeutics Reports Third Quarter 2021 Financial Results and Provides Corporate Update (PRNewswire) - "PN-235 moves into a psoriasis indication, Phase 2 study initiation planned for early 2022...Following a pre-specified interim analysis criteria, a portfolio decision was made to stop further development of the first-generation IL-23 receptor antagonist (IL-23R) candidate PTG-200 (JNJ-67864238), in favor of continued development of the two second generation candidates PN-235 (JNJ-77242113) and PN-232 (JNJ-75105186) with superior product profiles....Additionally, we are highly encouraged with the rate of enrollment in the Phase 2 study of our oral alpha-4-beta-7 integrin antagonist PN-943, for ulcerative colitis, an indication with a large patient population and unmet treatment need. We maintain our guidance of a data readout in Q2 2022..."

Discontinued • P2 data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Psoriasis

Protagonist Therapeutics Reports Second Quarter 2021 Financial Results and Recent Company Progress (PRNewswire) - "PN-943:...significant progress in the enrollment and execution of the Phase 2 study of PN-943 in ulcerative colitis, revising guidance in anticipation of a sooner-than-expected data readout of the completed study. The Company expects to report results of the completed study in the second quarter of 2022...Research and Development ('R&D') Expenses: R&D expenses for the three and six months ended June 30, 2021 were $26.4 million and $50.7 million, respectively, as compared to $20.3 million and $39.0 million, respectively, for the same periods of 2020. The increases were primarily due to additional costs associated to advancing our clinical trials with our pipeline assets rusfertide and PN-943..."

Commercial • P2 data • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist Reports First Quarter 2021 Financial Results and Provides Corporate Update (PRNewswire) - "In the second quarter of 2021, Protagonist expects to dose the first subject in the Phase 1 study of PN-232. The Company expects to complete both this trial and the Phase 1 trial of PN-235 in the second half of 2021...Research and Development ('R&D') Expenses: R&D expenses for the first quarter 2021 were $24.2 million as compared to $18.8 million for the same period of 2020. The increase was primarily due to costs associated with advancing our clinical trials with our pipeline assets of rusfertide and PN-943, as well as our three IL-23 receptor antagonist assets under the Janssen collaboration (PTG-200, PN-235 and PN-232)."

Commercial • New P1 trial • Trial completion date • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Single- and Multiple-Dose Pharmacokinetics and Pharmacodynamics of PN-943, a Gastrointestinal-Restricted Oral Peptide Antagonist of α4β7, in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "PN-943 was generally well tolerated following single and multiple oral doses with low systemic exposure. Twice-daily dosing resulted in sustained pharmacokinetics and pharmacodynamics, supporting further investigation in efficacy studies."

Clinical • Journal • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist Therapeutics Reports Fourth Quarter and Full Year 2020 Financial Results and Corporate Update (PRNewswire) - "The 150-patient Phase 2 study (the 'IDEAL' study) evaluating the safety, tolerability and efficacy of PN-943 in patients with moderate to severe ulcerative colitis is underway and completion is expected in 2022...The Phase 2A proof-of-concept study (the 'PRISM' study) with the first-generation candidate PTG-200 for patients with moderate to severe Crohn's disease is continuing to enroll in 2021."

Trial completion date • Inflammatory Bowel Disease • Ulcerative Colitis

PN-943 in Adults With Moderate to Severe Active Ulcerative Colitis (UC) (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Protagonist Therapeutics, Inc.; Trial completion date: Oct 2022 ➔ Jun 2023; Trial primary completion date: Nov 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

PN-943 in Adults With Moderate to Severe Active Ulcerative Colitis (UC) (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Protagonist Therapeutics, Inc.

Clinical • New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Protagonist Therapeutics Reports Second Quarter Financial Results and Provides Corporate Update (PRNewswire) - "We recently initiated screening of patients for our Phase 2 study of PN-943 in ulcerative colitis. Finally, we are well financed and recently raised $122 million...which enables us to support planned operations through mid-2023....Research and Development ('R&D') expenses for the three and six months ended June 30, 2020, were $20.3 million and $39.0 million, respectively...primarily due to increased activities in advancing our ongoing clinical trial for...preparedness for PN-943 Phase 2 study in ulcerative colitis, and our IL-23 receptor antagonist research collaboration activities with Janssen Biotech."

Commercial • Trial status • Inflammatory Bowel Disease • Ulcerative Colitis

A trial to investigate the safety and efficacy of PN-943 in patients with moderate or severe Ulcerative Colitis (a long-term condition where the colon and rectum become inflamed) (clinicaltrialsregister.eu) - P2; N=150; Ongoing; Sponsor: Protagonist Therapeutics, Inc

Clinical • New P2 trial

Protagonist Therapeutics reports first quarter financial results and provides corporate update (PRNewswire) - "The results of the PTG-300 beta-thalassemia Phase 2 study will be presented at an upcoming medical conference in the second quarter of 2020....The Company is discontinuing clinical development for PTG-300 in beta-thalassemia and myelodysplastic syndromes....A Phase 2 study of PN-943 in approximately 150 patients with moderate-to-severe ulcerative colitis is currently planned."

Discontinued • New P2 trial • P2 data • Anemia • Beta-Thalassemia • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

PN-943, AN ORAL α4β7 INTEGRIN ANTAGONIST, INHIBITS MADCAM1-MEDIATED PROLIFERATION AND CYTOKINE RELEASE FROM CD4+ T-CELLS INDEPENDENT OF TRAFFICKING (DDW 2020) - "Saturation of circulating T-cell α4β7 by vedolizumab is not sufficient for optimal efficacy (Ungar et al, Clin Gastroenterol Hepatol 2018); and PTG-100, a PN-943 analog, showed evidence of remission in Ulcerative Colitis patients at sub-saturating blood receptor occupancy (RO; Sandborn et al, UEGW 2018). Previous preclinical studies have shown PN-943 affects trafficking of CD4+ T cells (Mattheakis et al, DDW 2019). Here, we demonstrate the ability of PN-943 to inhibit MAdCAM1-mediated proliferation and cytokine release as another mechanism which may control chronic inflammation occurring in the gut of IBD patients. This finding supports an intervention strategy that is best exploited by an oral GI-restricted approach, whereby PN-943 is delivered locally and directly blocks α4β7 function in the GI"

Gastroenterology • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IFNG • IL17A • IL4 • IL6

Protagonist Therapeutics reports fourth quarter and full year 2019 financial results (PRNewswire) - "Protagonist Therapeutics and Janssen Biotech are jointly conducting the development of PTG-200 (or JNJ-67864238) through completion of a Phase 2a study in patients with moderate-to-severe Crohn's disease, with the anticipation of completion in the first half of 2021....The Company plans to initiate a Phase 2 study in patients with ulcerative colitis in the second quarter of 2020, with topline data expected in the second half of 2021."

Enrollment status • New P2 trial • P2 data

PN-943, an oral α4β7 integrin antagonist, inhibits MAdCAM1-mediated proliferation and cytokine release from CD4+ T cells independent of trafficking (ECCO-IBD 2020) - "Saturation of circulating T-cell α4β7 by vedolizumab is not sufficient for optimal efficacy; and PTG-100, a PN-943 analogue, showed evidence of clinical and histological remission in ulcerative colitis patients at sub-saturating blood receptor occupancy (%RO). Consistent with the requirement for a locally acting drug, 30 mg/kg oral dosing in mice demonstrated high exposure (n = 6, 39 nM) and occupancy of T-cell α4β7 (n = 6, 92%) in the GI compared within the blood.Conclusion The α4β7-MAdCAM1 interaction promoted β7+CD4+ T-cell proliferation and cytokine release, which may contribute to chronic inflammatory responses occurring in the diseased gut of IBD patients independent of T-cell trafficking. PN-943 inhibition of MAdCAM1-mediated signalling through α4β7 supports the potential therapeutic advantages for an oral GI-restricted approach, whereby PN-943 is delivered locally and directly blocks α4β7 function in the GI."

IFNG • IL13 • IL17A • IL4 • IL6