UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

 

Date of Report (Date of earliest event reported): October 22, 2018

 

PROTAGONIST THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

 

Delaware

 

001-37852

 

98-0505495

(State or other jurisdiction
of incorporation)

 

(Commission
File Number)

 

(IRS Employer
Identification No.)

 

Protagonist Therapeutics, Inc.

7707 Gateway Blvd., Suite 140

Newark, California 94560-1160

(Address of principal executive offices, including zip code)

 

(510) 474-0170

(Registrant’s telephone number, including area code)

 

Not Applicable

(Former name or former address, if changed since last report.)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

o      Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

o      Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

o      Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

o      Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company x

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.   x

 

 

 


 

Item 7.01              Regulation FD Disclosure.

 

Attached hereto as Exhibit 99.1 is a copy of a presentation that the Company intends to use in connection with a presentation on October 22, 2018.

 

The information in this Current Report on Form 8-K, including the attached Exhibit 99.1, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, except as expressly set forth by specific reference in such filing to this Current Report on Form 8-K.

 

Item 9.01              Financial Statements and Exhibits.

 

(d) Exhibits

 

99.1

Protagonist Therapeutics, Inc. Presentation dated October 22, 2018

 

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SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

Protagonist Therapeutics, Inc.

 

 

 

Dated: October 22, 2018

 

 

 

 

 

 

By:

/s/ Thomas P. O’Neil

 

 

Thomas P. O’Neil

 

 

Chief Financial Officer

 

 

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Exhibit 99.1

PTG-100, an Oral Gut-Restricted Peptide 47 Antagonist, Induces Clinical and Histologic Remission in Patients with Moderate to Severely Active Ulcerative Colitis William J Sandborn, Brian Bressler, Scott Lee, Raj Bhandari, Bittoo Kanwar, Lucio Tozzi, Richard Shames, Geert D’Haens, Jean-Frederic Colombel, Stefan Schreiber, Silvio Danese, Rish K. Pai, Brian Feagan

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Disclosures Dr. Sandborn reports consulting fees from Abbvie, Akros Pharma, Allergan, Ambrx Inc., Amgen, Ardelyx, Arena Pharmaceuticals, Atlantic Pharmaceuticals, Avaxia, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Conatus, Cosmo Technologies, Escalier Biosciences, Ferring, Ferring Research Institute, Forward Pharma, Galapagos, Genentech, Gilead Sciences, Immune Pharmaceuticals, Index Pharmaceuticals, Janssen, Kyowa Hakko Kirin Pharma, Lilly, Medimmune, Mesoblast, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Otsuka, Palatin, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Qu Biologics, Regeneron, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Salix, Seattle Genetics, Seres Therapeutics, Shire, Sigmoid Biotechnologies, Takeda, Theradiag, Theravance, Tigenix, Tillotts Pharma, UCB Pharma, Vascular Biogenics, Vivelix; research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos; payments for lectures/speakers bureau from Abbvie, Janssen, Takeda; and holds stock/stock options in Escalier Biosciences, Oppilan Pharma, Precision IBD, Progenity, Ritter Pharmaceuticals 2

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PTG-100 Oral 47-specific, GI-restricted, Targeted Therapy for IBD Briskin M, et al Am J Pathol. 1997;151:97-110 3 • First-in-class potential as a GI-restricted 47-specific blocker – Small constrained peptide – ~2.5 kDa • 47 integrin, a clinically validated IBD target • Oral, once daily dosing • Blood-based PD biomarkers reflect local target engagement with effects on trafficking

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Phase 2 PROPEL Study in Ulcerative Colitis Randomized, double-blind, placebo-controlled adaptive parallel design • • 12 week induction study, QD dosing Primary endpoints: Clinical remission, safety and tolerability Score * change of one or more from baseline of clinical remission 4 Interim Analysis y analysis based on Criteria Stool Frequency Rectal Bleeding Endo-scopy Total Score 0-1* 0 0-1 0-2 Enrollment Criteria: •Mayo Score 6-12 •Central read endoscopic score > 2 •Biologics-naïve or TNF-experienced (< 50%) Placebo 150 mg QD 300 mg QD 900 mg QD Interim futilit 1° end point Adhering to the most current and stringent definition of clinical remission Interim Analysis n = 65 Moderate to severe UC N~260, ~100 sites

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Baseline Demographics Interim Analysis Dataset (n = 65) • Patients were balanced across all treatment arms 5 Demographic Placebo 150 mg 300 mg 900 mg Age (mean) 42.4 45.2 43.7 40.9 Gender (% M) 57 72 46 35 BMI (kg/m2) 23.4 25.7 24.4 24.4 Duration of UC (years) 7.5 5.1 6.9 5.6 Baseline Total Mayo Score 8 8.1 8.9 8.3 % TNF-experienced 29.4 37.5 31.3 43.8

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Interim Analysis Futile Outcome Driven by Unusually High Placebo Rates • • Interim outcome (n=65) declared futile by DMC and trial was No safety concerns were noted discontinued • A comprehensive data review was undertaken – – Operational misconduct and trial design issues were ruled out Issues with central endoscopy reading were identified • All 4 PBO clinical remitters were scored by a single reader • Friability incorrectly scored by reader 6 •An independent blinded re-read of endoscopy videos was conducted by Robarts Clinical Trials •Unusually high placebo effect was observed: 4/17 (23.5%) – Historic average for similar trials is ~ <6%

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Re-analysis Based on Endoscopy Re-Reads Interim dataset summary (n = 65) Response • • 1/17 (5.9%) placebo rate of remission; this indicated non-futile outcome Efficacy observed in PTG-100 higher dose arms 7 Remission Endoscopic 150 mg 1/16 (6%) 1/16 (6%) 300 mg 2/16 (13%) 2/16 (13%) 900 mg 3/16 (19%) 3/16 (19%) PBO 1/17 (6%) 1/17 (6%) Remission Endoscopic Response 150 mg 1/16 (6%) 1/16 (6%) 300 mg 2/16 (13%) 2/16 (13%) 900 mg 3/16 (19%) 4/16 (25%) PBO 4/17 (24%) 4/17 (24%) •Re-read •Normal Placebo Rate •Original Reads •High Placebo Rate

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Re-analysis Based on Endoscopy Re-Reads Full Dataset Summary (n = 83) • • Placebo remission rate in line with historical norms (1/21, 4.8%) Efficacy observed in PTG-100 higher dose arms –900 mg arm showed 11% delta over PBO 8 Criteria Placebo 150 mg 300 mg 900 mg # Patients 21 22 21 19 Clinical Remission 1 (4.8%) 2 (9.1%) 2 (9.5%) 3 (15.8%) Endoscopic Response 1 (4.8%) 2 (9.1%) 3 (14.3%) 3 (15.8%) Blinded endoscopy re-reads on complete data set (n=83)

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PTG-100 is Full Analysis Safe and Well-Tolerated Set (n=98) •All SAEs and AEs leading to discontinuation were due to worsening of UC •Cause of death in placebo patient: – Mesenteric ischemia due to complications of UC surgery 9 PBO (n=21) 150 mg (n=22) 300 mg (n=25) 900 mg (n=20) Subjects with at least one AE 10 (48%) 6 (27%) 10 (40%) 12 (60%) Subjects with SAEs 1 (4.8%) 2 (9.1%) 1 (4%) 1 (5%) Discontinuations (n=25/arm) 3 (14%) 3 (14%) 4 (16%) 2 (10%) AEs leading to d/c 1 (4.8%) 2 (9.1%) 0 (0%) 1 (5%) Deaths 1 (4.8%) 0 (0%) 0 (0%) 0 (0%)

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Histopathology Analysis Robarts Histopathology Index (RHI) • Four components – – – – Chronic Inflammatory Infiltrate Lamina Propria Neutrophils Epithelial Neutrophils Erosions/Ulcerations • • Included patients with disease activity at baseline (RHI > 3) Histologic remission defined as an RHI score <3 with no neutrophils, erosions, or ulcerations Mosli MH, Feagan BG, Zou G, et al Gut 2017;66:50-58 10

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Dose-dependent Increase in Rates of Histologic Remission Defined as an RHI score < 3 at Week 12 50 45 40 44% 35 30 25 20 15 10 5 0 PBO (n=13) 150 mg (n=13) 300 mg (n=9) 900 mg (n=16) 11 % Histologic Remission 22% 15% 0

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PTG-100 Does Not Require 100% Target Engagement in Blood for Clinical Efficacy 100 150mg 300mg 900mg Placebos 80 60 40 20 0 -20 -40 0 14 28 42 Day 56 70 84 • • The above data is consistent with previous pre-clinical colitis and Phase 1 PD results Receptor occupancy in blood and in the GI tissue are correlated in preclinical studies (data not shown) 12 Median Percent Baseline Normalized 47+ CD4+ T memory Receptor Occupancy

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PTG-100 Phase Conclusions 2 PROPEL Study These data must be interpreted with caution given that the re-read was post hoc, the sample size is relatively small, and changes in the outcome of a small number of patients led to different conclusions PTG-100 is safe and well-tolerated, and the totality of the data which include clinical, endoscopic, histologic, and biomarker data are consistent with both a biological and clinical response and demonstrated dose response Validation of GI-restricted approach with oral 47-integrin specific antagonist for potential treatment of UC. Current data warrants further clinical development ofPTG-100. 13 4 3 2 1 Initial erroneous central read endoscopy scores led to a futile outcome. Re-analysis based on endoscopy re-reads indicated a non-futile outcome and clinical efficacy in higher dose arms

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14 Thanks to the patients, families and investigators for their participation in the PROPEL study.

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