8-K
Protagonist Therapeutics, Inc (PTGX)
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): April 25, 2022
PROTAGONIST THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-37852 | 98-0505495 |
|---|---|---|
| (State or other jurisdiction<br><br>of incorporation) | (Commission<br><br>File Number) | (IRS Employer<br><br>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:
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|---|---|
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
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Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on whichregistered |
|---|---|---|
| Common Stock, par value $0.00001 | PTGX | The Nasdaq Stock Market LLC |
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 ¨
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. ¨
Item 7.01 Other Information.
PN-943 Phase 2 Trial Topline Data
On April 25, 2022, Protagonist Therapeutics, Inc. issued a press release announcing topline data from its Phase 2 clinical trial evaluating its product candidate PN-943 in ulcerative colitis and held an investor conference call to discuss the results.
The press release is attached hereto as Exhibit 99.1 and the presentation from the conference call is attached hereto as Exhibit 99.2.
Item 9.01 Financial Statementsand Exhibits.
(d) Exhibits
| Exhibit No. | Description |
|---|---|
| 99.1 | Protagonist Therapeutics, Inc. PN-943 Phase 2 Topline Data Press Release (April 25, 2022) |
| 99.2 | PN-943 Phase 2 Topline Data Investor Presentation (April 25, 2022) |
| 104 | Cover Page Interactive Data File (embedded within the inline XBRL document) |
The information in this report, including the exhibits hereto, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of Section 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained herein and in the accompanying exhibit shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission made by Protagonist Therapeutics, Inc., whether made before or after the date hereof, regardless of any general incorporation language in such filing.
SIGNATURE
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: April 25, 2022 | ||
| By: | /s/ Asif Ali | |
| Asif Ali | ||
| Executive Vice President, Chief Financial Officer |
Exhibit 99.1
Protagonist Therapeutics Announces Topline Datafrom Phase 2 IDEAL Study of PN-943 in Ulcerative Colitis
PN-943 achieved 27.5% clinical remission witha 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 validationfor oral, gut-restricted approach for ulcerative colitis via blockade of the alpha-4-beta-7-integrin pathway
Plans underway for a registrational Phase 3study anchored around twice daily 150 mg dose of PN-943, pending regulatory guidance
Protagonist to host a conference call todayat 6:00 p.m. ET
NEWARK, Calif., April 25, 2022 /PRNewswire/ -- Protagonist Therapeutics (Nasdaq: PTGX) today announced topline results from the Phase 2 IDEAL study evaluating PN-943 in patients with moderate-to-severe ulcerative colitis (UC).
"We are delighted with the strength of the results from the IDEAL study and look forward to working with the regulatory agencies as we prepare for a Phase 3 registrational program for PN-943 in moderate-to-severe ulcerative colitis," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist. "Our oral, gut-restricted alpha-4-beta-7-integrin antagonist agent PN-943 has demonstrated clinical efficacy on par with the approved injectable antibody drug working through the same biological target. We believe the results of the IDEAL study may be paradigm shifting and of broad scientific relevance in understanding IBD pathogenesis and gut-restricted drug development via intervention of the integrin-MAdCAM pathway. Based on its convenience of oral administration and the favorable efficacy and safety results observed to date, we believe that PN-943 has the potential to become a first-in-class, foundational oral medicine for individuals living with moderate-to-severe ulcerative colitis."
"With the IDEAL study, we have demonstrated clinical proof-of-concept and validation for potential treatment of ulcerative colitis via oral, gut-restricted blockade of the alpha-4-beta-7-integrin pathway," said Scott Plevy, M.D., Executive Vice President and Therapeutic Head of Gastroenterology at Protagonist. "The study assessed two doses of PN-943, 150 mg BID and 450 mg BID, and demonstrated a very clear and consistent treatment effect at the lower 150 mg BID dose across key endpoints. The dose response demonstrated by this study is consistent with several other modalities in the integrin pathway. The findings in the lower-dose arm provide consistent evidence of clinical efficacy and safety, and clear direction on the dosing regimen for the Phase 3 registrational program."
"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, M.D., M.S., the Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai, principal investigator for the IDEAL study and consultant to Protagonist. "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."
Summary of Key Results
IDEAL is a randomized, double-blinded, placebo-controlled, multicenter Phase 2 study to evaluate the safety and efficacy of PN-943, an oral, gut-restricted, alpha-4-beta-7-integrin antagonist. 159 patients with moderate-to-severe active UC were randomized to either twice daily (BID) with 450 mg or 150 mg PN-943, or placebo, for 12 weeks and analyzed for outcome measures.
While the 450 mg BID dose did not meet the prespecified primary endpoint, the 150 mg dose achieved a placebo versus treatment delta of 13% (p=0.08) in the modified Intent to Treat (mITT) group, and a delta of 16% (p=0.04) in the bio-naïve group. In addition, the 150 mg BID data showed strong concordance across multiple parameters including statistically significant histological remission and endoscopic improvement.
PN-943 150 mg BID dose forms the basis for a Phase 3 registrationalprogram
| · | 27.5%clinical remission vs 14.5% in placebo (delta 13%, p=0.08) for mITT analysis |
|---|---|
| · | 16%<br>delta in BIO-naïve population (p=0.04) |
| --- | --- |
| · | Strongconcordance with efficacy across multiple key secondary endpoints with statistically significant differences in histologic remission/improvement<br>and endoscopic improvement |
| --- | --- |
| · | Safety<br>analysis similar for the 150 mg BID dose versus the placebo group |
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Conference Call and Webcast Information
A conference call will take place today, April 25, 2022, at 6:00 p.m. ET.
Protagonist's management team will be joined by Bruce Sands, M.D., M.S., the Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai and principal investigator for the IDEAL study and consultant to Protagonist.
Live audio of the conference call will be simultaneously broadcast over the internet. The call will be available to investors, members of the news media, and the general public.
To access the live call, dial 1-877-870-4263 (U.S./Canada) or 1-412-317-0790 (international) five minutes prior to the call and ask to be joined to the Protagonist Therapeutics call (conference ID 10166546). A live and archived webcast will be accessible in the Investors section of the Company's website at www.protagonist-inc.com.
About Protagonist
Protagonist Therapeutics is a biopharmaceutical company with multiple peptide-based new chemical entities in different stages of clinical development, all derived from the Company's proprietary technology platform.
Protagonist's pipeline includes rusfertide, an investigational, injectable hepcidin mimetic currently in the REVIVE Phase 2 proof-of-concept clinical trial for polycythemia vera (PV), the PACIFIC Phase 2 study in PV subjects with high hematocrit levels, and a recently completed Phase 2a study for hereditary hemochromatosis. The Company has opened sites and initiated patient screening for VERIFY, a single, global Phase 3 randomized, placebo-controlled trial evaluating the efficacy and safety of a once weekly, subcutaneously self-administered dose of rusfertide.
The IDEAL Phase 2 study of PN-943 in moderate-to-severe ulcerative colitis concluded in April 2022. The results of this Phase 2 study supported advancement of the 150-milligram dose of PN-943 into a Phase 3 registrational study. Plans for the Phase 3 registrational study are underway. The Company is targeting ulcerative colitis as the initial indication.
Protagonist has granted Janssen an exclusive worldwide license to research, develop and commercialize oral IL-23 receptor antagonists based on the Company's intellectual property. Current development efforts are centered on PN-235, discovered by Protagonist and further developed in collaboration with Janssen. FRONTIER 1, a Phase 2b multicenter, randomized, placebo controlled, dose-ranging study to evaluate the safety and efficacy of PN-235 for the treatment of moderate-to-severe plaque psoriasis, commenced in early 2022.
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, our plans for further clinical development of PN-943 and the potential benefits of PN-943. 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 agreements, the impact of the current COVID-19 pandemic on our discovery and development efforts, the impact of the ongoing military conflict in Ukraine and Russia on any future studies, 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, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward- looking statements, whether as a result of new information, future events or otherwise, after the date of this press release.
CONTACT: Company: Jami Taylor – j.taylor@ptgx-inc.com; Investors: Kevin Murphy – protagonist@argotpartners.com; Media: Virginia Amann – VirginiaAmann@EntenteInc.com
Exhibit 99.2
1 PN - 943 Phase 2 Study Data Readout Dinesh V. Patel, PhD | President & CEO April 25, 2022
Today’s Agenda 2 Introduction: Dinesh V. Patel, PhD, President & CEO Data readout from the Phase 2 IDEAL Study of PN - 943 in Ulcerative Colitis (UC): Scott Plevy, MD, Executive Vice President & Therapeutic Head, Gastroenterology Reflections on the data and the unmet need in UC : Bruce Sands, MD, MS, the Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai. Principal investigator of the Phase 2 study of PN - 943 in UC, consultant to Protagonist Concluding remarks : Dinesh V. Patel, PhD Analyst Q&A : Operator - moderated Q&A Participants: - Dinesh V. Patel, PhD - Scott Plevy, MD - Bruce Sands, MD, MS - Samuel Saks, MD, Clinical Development Advisor - David Liu, PhD, Chief R&D Strategy Officer - Suneel Gupta, PhD, Clinical Development Officer - Asif Ali, Chief Financial Officer - Paula O’Connor, MD, SVP of Clinical Developmen
Forward - looking Statements 2 This presentation and the accompanying oral presentation contain forward - looking statements made pursuant to the safe harbor pro visions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this pre sentation, including statements regarding our future results of operations and financial position, business strategy, product candidates, capital res ources, potential markets for our product candidates, enrollment in our clinical trials, any potential impact on our business related to COVID - 19, our pot ential receipt of milestone payments and royalties under our Collaboration Agreement with Janssen Biotech, Inc., are forward - looking statements. In some ca ses, you can identify forward - looking statements by terminology such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potentially” “predict,” “should,” “will” or the negative of these terms or other similar expressions. The forward - looking statements made in this presentation involve known and unknown risks, uncertainties and other important fact ors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievemen ts expressed or implied by the forward - looking statements. These forward - looking statements are subject to risks and uncertainties, including those discuss ed in Protagonist’s filings with the Securities and Exchange Commission, including in the “Risk Factors” and “Management’s Discussion and Analysi s o f Financial Condition and Results of Operations” sections of most recently filed periodic reports on Form 10 - K and Form 10 - Q and subsequent filings an d in the documents incorporated by reference therein. Because forward - looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward - looking statements as pre dictions of future events. The events and circumstances reflected in our forward - looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward - looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward - looking statements contained herein, whether as a result of any new information, future events, changed circumstances or othe rwi se. This presentation concerns products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. They are currently limited by Federal law to investigational use, and no representation is made as to their s afe ty or effectiveness for the purposes for which they are being investigated. The trademarks included herein are the property of the owners thereof and are us ed for reference purposes only. Such use should not be construed as an endorsement of such products. Nothing contained in this presentation i s, or should be construed as, a recommendation, promise or representation by the presenter or Protagonist or any director, employee, agent or ad visor of Protagonist. This presentation does not purport to be all inclusive or to contain all the information you may desire.
PN - 943 Phase 2 UC IDEAL Study Topline Results and Next Steps 4 • PN - 943 is an oral, gut - restricted a4b7 - integrin antagonist – ‘Oral Entyvio’ equivalent • Achieved clinical proof - of - concept and validation for oral, gut - restricted approach for ulcerative colitis via blockade of the a4b7 - integrin pathway • The current data supports moving PN - 943 in a phase 3 UC registrational study – 150 mg bid dose has efficacy similar to Entyvio ( vedoluzimab ) – Strong concordance between clinical remission and secondary endpoints (histology and endoscopy) • Convenience, efficacy, safety, first - in - class, foundational oral medicine for UC
PTG - 100 Ph2A Efficacy Similar to Other IBD Targeted Therapy Drugs 5 *Anti - MadCam mAb * No central read endoscopy ( Entyvio ) PTG - 100, 900 mg q.d . dose showed 44% histological remission (RHI)
The Outcome of Phase 2 IDEAL Study will Inform Phase 3 Decisions • Phase 2 data in UC with various candidates spanning different mechanism of actions – Large confidence intervals, influenced by study design, duration, size, demographics, & criteria – Phase 2 outcomes has generally predicted efficacy in Phase 3 6 Translating H Historical Ph2, Ph3, and Approval Data in UC 2 ➞ Phase 3 ➞ Approval* Candidate MoA Clinical Remission Delta Approval Phase 2 Phase 3 Vedolizumab (Entyvio ® ) 1 a4b7 integrin 19% 11.5% ✓ Ozanimod ( Zeposia ® ) 2 S1P 10% 12.4% ✓ Upadacitinib ( Rinvoq ® ) 3 JAK 19.6% 21/29.5% ✓ (black box) 1. Feagan , B. G., Greenberg, G. R., Wild, G., Fedorak , R. N., Paré , P., McDonald, J. W., ... & Vandervoort , M. K. (2005). Treatment of ulcerative colitis with a humanized antibody to the α4β7 integrin. New England Journal of Medicine , 352 (24), 2499 - 2507; Feagan , B. G., Rutgeerts , P., Sands, B. E., Hanauer , S., Colombel , J. F., Sandborn , W. J., ... & Parikh, A. (2013). Vedolizumab as induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine , 369 (8), 699 - 710. 2. Sandborn , W. J., Feagan , B. G., Wolf, D. C., D’Haens , G., Vermeire , S., Hanauer , S. B., ... & Olson, A. (2016). Ozanimod induction and maintenance treatment for ulcerative colitis. New England Journal of Medicine , 374 (18), 1754 - 1762; Sandborn , W. J., Feagan , B. G., D’Haens , G., Wolf, D. C., Jovanovic, I., Hanauer , S. B., ... & Danese , S. (2021). Ozanimod as induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine , 385 (14), 1280 - 1291. 3. Danese , S., Vermeire , S., Zhou, W., Pangan , A., Siffledeen , J., Hébuterne , X., ... & Pannaccione , R. (2021). OP24 Efficacy and safety of upadacitinib induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from the phase 3 U - ACHIEVE study. Journal of Crohn's and Colitis , 15 (Supplement_1), S022 - S024.; Vermeire , S., Danese , S., Zhou, W., Pangan , A., Greenbloom , S., D’Haens , G., ... & Panaccione , R. (2021). OP23 Efficacy and safety of upadacitinib as induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from phase 3 U - ACCOMPLISH study. Journal of Crohn's & Colitis , 15 (Suppl 1), S021. • Phase 2 data will provide specific guidance for phase 3 program on – Go/No - go decision ✓ – Dose selection ✓ – Powering of registrational primary and secondary endpoints ✓ *Cross trial comparisons complicated by different inclusion criteria, patient populations, primary endpoint definitions, timi ng of primary endpoint, phase of clinical development
IDEAL: PN - 943 Phase 2 UC Study Design 7 Part - 1: Induction Part - 2: Extended Treatment Period 5 weeks 12 weeks 40 Weeks Week 52 Randomize (n=150) Placebo BID (n=55) Active Drug 450 mg BID (n=53) Active Drug 150 mg BID (n=51) PN - 943 Adult Patients with UC N≈169 ( mITT = 159) Eligibility: • Moderate – Severe UC • 3 - Component Mayo Score 5 - 9 points Inclusion: • B io - naïve and bio - experienced patients Primary endpoint: • C linical Remission* at Week 12 (450 mg bid vs. placebo) Secondary endpoints: • C linical Remission* at Week 12 (150 mg bid vs. placebo) • Endoscopic, histopath , mucosal Exploratory endpoints: • Blood %RO, FCP Induction Phase of study completed and preliminary data readout presentation aligned to guidance of first half of Q2 2022 * Definition of clinical remission based on Adapted Mayo Score: • Stool Frequency subscore (SFS) ≤1 • Rectal Bleeding subscore (RBS) of 0 • Endoscopy subscore ≤1
Enrollment by Country 8 Percentages are based on the total number of subjects in each column Country Subjects Screened (N=338) n (%) Subjects Randomized (N=169) n(%) Poland 163 (48.2) 97 (57.4) Russia 45 (13.3) 24 (14.2) United States 60 (17.8) 13 ( 7.7) Georgia 20 ( 5.9) 10 ( 5.9) Ukraine 15 ( 4.4) 9 ( 5.3) Italy 11 ( 3.3) 5 ( 3.0) Korea, Republic of 5 ( 1.5) 5 ( 3.0) Hungary 3 ( 0.9) 2 ( 1.2) Canada 10 ( 3.0) 1 ( 0.6) Austria 2 ( 0.6) 1 ( 0.6) Serbia 2 ( 0.6) 1 ( 0.6) Germany 1 ( 0.3) 1 ( 0.6) Bulgaria 1 ( 0.3) 0 Total 338 169
9 Placebo (N=55) PN - 943 150mg bid (N=51) PN - 943 450mg bid (N=53) Age yrs , mean (SD) 38 (10.6) 42 (12.6) 38 (13.3) Male sex, n (%) 35 (63.6) 26 (51.0) 33 (62.3) Weight (kg), mean (SD) 71.7(17.39) 74.3 (15.61) 74.4 (15.18) BMI, mean (SD) 24.2 (4.80) 25.7 (5.11) 24.6 (4.18) Duration of UC, months Mean (SD) 77.0 (66.0) 66.4 (61.91) 72.8 (64.87) Median (min - max) 58.7(3.9, 247.2) 51.55 (6.0, 275.5) 48.66 (4.6, 244.6) Disease extent, n (%) Proctitis 1 ( 1.8) 2 ( 3.9) 1 ( 1.9) Left sided colitis 38 (69.1) 34 (66.7) 33 (62.3) Pan colitis 16 (29.1) 15 (29.4) 19 (35.8) Baseline modified MCS Mean (SD) 6.95 (1.061) 6.76 (0.992) 6.81 (1.144) Median (min - max) 7 (5, 9) 7 (5, 9) 7 (4, 8) Current oral corticosteroids n (%) 9 (16.4) 5 (9.8) 15 (28.3) Immunosuppressants n (%) 11 (20.0) 6 (11.8) 10 (18.9) Exposure to biologics, n (%) 10 (18.2%) 5 ( 9.8%) 6 (11.3%) Demographic and Disease Characteristics at Baseline – mITT Population
30.2% 13/43 17 .0% 8/47 14 % 6/43 0 5 10 15 20 25 30 35 150 mg BID 450 mg BID Placebo Clinical Remission (%) mITT Bio - Naïve ( Δ 16%) 27.5 % 14/51 15.1 % 8/53 14.5 % 8/55 0 5 10 15 20 25 30 150 mg BID 450 mg BID Placebo Clinical Remission (%) mITT ALL ( Δ 13%) CONFIDENTIAL 10 P=0.035 Clinical Remission 13% D vs placebo for PN - 943 in mITT and 16% D in BIO - Naive P=0.081
37.2 % 16/43 23.4 % 11/47 14.3 % 7/49 0 5 10 15 20 25 30 35 40 150 mg BID 450 mg BID Placebo Histologic Remission (%) (RHI≤6) 36.4 % 16/44 20.8 % 10/48 16 .0% 8/50 0 5 10 15 20 25 30 35 40 150 mg BID 450 mg BID Placebo Histologic Improvement ( Geboes <3.1) CONFIDENTIAL 11 P=0.0107 P=0.0213 Histologic Remission and Improvement Statistically Significant Differences D 23% in remission D 20% in improvement ( Δ 23%) ( Δ 20%)
11.8 % 6/51 1.9 % 1/53 3.6 % 2/55 0 2 4 6 8 10 12 14 150 mg BID 450 mg BID Placebo Endoscopic Remission* (%) (ESS=0) 43.1 % 22/51 20.8 % 11/53 16.4 % 9/55 0 5 10 15 20 25 30 35 40 45 50 150 mg BID 450 mg BID Placebo Endoscopic Improvement** ( ESS= 0 or 1) 12 P=0.0023 Endoscopic Remission and Improvement Strong improvement in quantitative endoscopic parameters ** ESS = 0 or 1 *ESS = 0 ( Δ 8.2 %) ( Δ 26.7%)
23% 7% 0% 5% 10% 15% 20% 25% Vedo Placebo Clinical Remission (%) Vedolizumab* 30.2 % 14 % 0 5 10 15 20 25 30 35 150 mg BID Placebo Clinical Remission (%) PN943 13 Clinical Remission Comparison in Bio - Naive PN - 943 Vs Vedolizumab efficacy in Phase 2 Studies Δ 16.3% Δ 15.5% * Feagan 2017; Clin. Gastroenterology & Hepatology 15: 229 - 239
Safety Summary 14 • Generally well tolerated • No drug discontinuation from AEs • No drug related SAEs • Safety analysis similar for the 150 mg BID dose versus the placebo group * pre - existing, not drug related System Organ Class Preferred Term Placebo (N=57) n(%) PN-943 150mg (N=55) n(%) PN-943 450mg (N=57) n(%) Total (N=169) n(%) Total Number of TEAEs 47 46 54 147 Number Of Subjects With At Least One TEAE 22 (38.6) 21 (38.2) 30 (52.6) 73 (43.2) Infections And Infestations 2 ( 3.5) 7 (12.7) 12 (21.1) 21 (12.4) Covid-19 1 ( 1.8) 2 ( 3.6) 3 ( 5.3) 6 ( 3.6) Nasopharyngitis 0 1 ( 1.8) 3 ( 5.3) 4 ( 2.4) Upper Respiratory Tract Infection 1 ( 1.8) 1 ( 1.8) 1 ( 1.8) 3 ( 1.8) Urinary Tract Infection 0 0 2 ( 3.5) 2 ( 1.2) Cervicitis 0 0 1 ( 1.8) 1 ( 0.6) Conjunctivitis 0 1 ( 1.8) 0 1 ( 0.6) Cytomegalovirus Infection 0 0 1 ( 1.8)* 1 ( 0.6) Fungal Skin Infection 0 1 ( 1.8) 0 1 ( 0.6) Hordeolum 0 0 1 ( 1.8) 1 ( 0.6) Respiratory Tract Infection 0 0 1 ( 1.8) 1 ( 0.6) Respiratory Tract Infection Viral 0 0 1 ( 1.8) 1 ( 0.6) Rhinitis 0 1 ( 1.8) 0 1 ( 0.6) Gastrointestinal Disorders 7 (12.3) 5 ( 9.1) 6 (10.5) 18 (10.7) Colitis Ulcerative 2 ( 3.5) 1 ( 1.8) 2 ( 3.5) 5 ( 3.0) Nausea 1 ( 1.8) 3 ( 5.5) 0 4 ( 2.4)
15 PN - 943 Trough Concentrations and Receptor Occupancy 0 4 8 12 0 3 6 9 12 Weeks P N - 9 4 3 ( n g / m L ) 0 4 8 12 0 20 40 60 80 100 120 Weeks R e c e p t o r O c c u p a n c y ( % )
Inverse D ose R esponse 16 • A bell - shaped dose response in Phase 2 UC studies is a frequent occurrence across multiple therapies that block the a4b7 integrin/ MAdCAM pathway – Observed since 1997 but still not fully understood – Decisions made to move into Phase 3 trials based on identification of an effective Phase 2 dose • A potential scientific explanation is based on the role of regulatory T cells (Treg) that dampen immune function – “Decreased activity (of Ontamalimab ) at increased doses is related to over - depletion of regulatory T cells …and other leukocyte subsets known to express a4b7 integrin, including intraepithelial lymphocytes, mucosa - associated invariant T cells, and eosinophils…” ( Vermeire , Lancet, 2017) • In chronic inflammatory diseases like IBD disease like UC, the objective is to block effector T cell (Teff) but not Treg function
Clinical Evidence of Bell Shaped Dose Response in UC Studies 17 Anti - a4b7 Integrin Antibody Vedolizumab (VDZ) Ph3 Exposure - Response for Clinical Remission with VDZ Treatment* *Becker, Gut, 2021
Clinical Evidence of Bell Shaped Dose Response in UC Studies 18 Anti - MAdCAM - 1 Antibody Ontamalimab (SHP647/PF - 00547659) Ph2 Clinical Remission at Week 12 By Anti - MAdCAM Treatment * * Vermeire , Lancet, 2017
Clinical Evidence of Bell Shaped Dose Response in UC Study 19 Anti - IL - 23 Antibody - Mirikizumab 4.8 15.9 22.6 11.5 0 5 10 15 20 25 30 Mirikizumab Clinical Remission (%) Placebo 50 mg (N=63) 200 mg (N=62) 600 mg (N=61) * Sandborn, Gastroenterology, 2020 Ph2 Clinical Remission by Mirikizumab IL - 23 Antagonist Treatment*
• PN - 943 150 mg BID appears to be a safe & effective dose – 27.5% Clinical remission vs 14.5% in placebo (delta 13%, p = 0.08) for mITT analysis ▪ 16% delta in BIO - naïve population (p = 0.04) – Strong concordance with efficacy across multiple key secondary endpoints with statistically significant differences in histologic remission/improvement and endoscopic improvement at the 150 mg BID dose – Confirmation of clinical effect with equivalent dose of PTG - 100 (900 mg QD) in PROPEL [150x2 (bid) x 3 (potency)] • Taken together, these results show that PN - 943 exerts a gut restricted MOA in the local tissue environment – Confirmatory of our original TPP of ‘Entyvio in a pill’ like efficacy • Safety analysis similar for the 150 mg BID dose versus the placebo group • No correlation between clinical efficacy for gut - restricted PN - 943 and blood PK and %RO • Inverse dose response demonstrated, consistent with several other modalities in the integrin pathway • The IDEAL study supports further development of PN - 943 in UC registrational trials Preliminary Conclusions and Next Steps 20
PN - 943 Phase 2 UC IDEAL Study Topline Results and Next Steps 21 • PN - 943 is an oral, gut - restricted a4b7 - integrin antagonist – ‘Oral Entyvio’ equivalent • Achieved clinical proof - of - concept and validation for oral, gut - restricted approach for ulcerative colitis via blockade of the a4b7 - integrin pathway • The current data supports moving PN - 943 in a phase 3 UC registrational study – 150 mg bid dose has efficacy similar to Entyvio ( vedoluzimab ) – Strong concordance between clinical remission and secondary endpoints ( histo - remission) • Convenience, efficacy, safety, first - in - class, foundational oral medicine for UC
Programs Candidates Study Phase 1 Phase 2 Phase 3 Key Milestones HEMATOLOGY & BLOOD DISORDERS Hepcidin Mimetic Rusfertide (PTG - 300) s.c. POLYCYTHEMIA VERA (PV) VERIFY 300 - 11 • Patient screening underway REVIVE 300 - 04 • Enrollment completed • Updates at 2022 conferences PACIFIC 300 - 08 • All patients resumed dosing in OLE HEREDITARY HEMOCHROMATOSIS (HH) 300 - 06 • Clinical PoC established INFLAMMATORY & IMMUNOMODULATORY DISEASES Oral GI Restricted ⍺ 4β7 - Integrin Antagonist PN - 943 IDEAL • 159 patient study • Topline data supportive of moving into Ph3 study • Ph3 planning underway Oral IL - 23R Antagonist PN - 235 • Psoriasis 240 patient study initiated • IBD Ph2 Initiation in 2H 2022 Product portfolio 22 Addressing unmet needs in multiple indications with multi - billion - dollar market potential PV Ph2 PoC trial Ulcerative Colitis (UC) Ph2 PoC PV Ph2 in patients with elevated Hct (>48%) Psoriasis Ph2b PoC trial HH Ph2 PoC PV Ph3 trial
Thank you 23