Icotrokinra Clinical Study Results Demonstrate its Potential to Shift Treatment Paradigm and Set a New Standard for Treatment in Plaque Psoriasis Nearly half of patients with moderate-to-severe plaque psoriasis (PsO) tre

Icotrokinra Clinical Study Results Demonstrate

its Potential to Shift Treatment Paradigm and Set a New Standard for Treatment in Plaque Psoriasis

Nearly half of patients with moderate-to-severe

plaque psoriasis (PsO) treated with icotrokinra achieved completely clear skin (IGA 0) at Week 24 in Phase 3 ICONIC-LEAD study

Topline results from Phase 3 ICONIC-ADVANCE

1&2 studies show icotrokinra achieved co-primary endpoints and showed superiority to deucravacitinib in moderate-to-severe PsO

Results pave the way to initiate the first-ever

head-to-head study (ICONIC-ASCEND) seeking to demonstrate the superiority of a pill versus injectable biologic in moderate-to-severe

Calif., March 8, 2025 - Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") today

announced new icotrokinra (JNJ-2113) data from the comprehensive Phase 3 clinical program and the planned initiation of the first-ever

head-to-head study in plaque psoriasis (PsO) seeking to demonstrate the superiority of an oral pill, icotrokinra, compared to an injectable

biologic, ustekinumab. Icotrokinra is a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor

and is being studied in adults and adolescents 12 years of age and older with moderate-to-severe plaque PsO.

Data from the Phase 3 ICONIC-LEADa

study, presented as a late-breaking abstract at the 2025 American Academy of Dermatology (AAD) Annual Meeting, show once daily icotrokinra

demonstrated significant skin clearance and a favorable safety profile in adults and adolescents 12 years of age and older with moderate-to-severe

Key findings from the ICONIC-LEAD

Results from a subgroup analysis of the ICONIC-LEAD

study evaluating icotrokinra in the adolescent population will be presented at a forthcoming medical meeting.

Additionally, topline results from

the icotrokinra versus deucravacitinib Phase 3 ICONIC-ADVANCE 1&2d studies are summarized below:

Based on the positive outcomes of the ADVANCE 1&2 studies, our

partner Johnson & Johnson is initiating the Phase 3 ICONIC-ASCENDe study, the first-ever head-to-head study seeking

to demonstrate the superiority of an oral pill, icotrokinra, compared to an injectable biologic, ustekinumab.

new results from the superiority ICONIC-ADVANCE 1&2 studies involving head-to-head comparison with the oral therapeutic deucravacitinib,

combined with the results from the ICONIC-LEAD study, reinforce icotrokinra's potential as a paradigm shifting, highly effective

first- and only-in-class targeted oral IL-23 receptor antagonist for treatment of psoriasis," said Dinesh V. Patel, Ph.D.,

President and Chief Executive Officer at Protagonist. "Icotrokinra offers a standout combination of complete skin clearance and

favorable safety profile in a once-daily pill and continues to establish itself as a potential first-line systemic therapy for psoriasis.

We're very excited about the continued expansion of the ICONIC clinical development program, as exemplified by the initiation of

the phase 3 ICONIC-ASCEND superiority study of icotrokinra versus ustekinumab."

ICONIC-LEAD is a Phase 3 randomized controlled trial (RCT) evaluating the efficacy and safety of icotrokinra compared with placebo

in 684 participants (icotrokinra=456; placebo=228) 12 years of age or older with moderate-to-severe plaque PsO, with the higher efficacy

bar of PASI 90 and IGA score of 0/1 with at least a 2-grade improvement as co-primary endpoints. ICONIC-LEAD enrolled 66 adolescent patients.

b. The IGA is a five-point scale with a severity

score ranging from 0 to 4, where 0 indicates clear, 1 is minimal, 2 is mild, 3 is moderate and 4 indicates severe disease.iv

c. The PASI score grades the amount of surface

area on each body region that is covered by psoriasis plaques and the severity of plaques for their redness, thickness and scaliness.v

PASI 90 corresponds to an improvement of >=90% in PASI score from baseline.v

ICONIC- ADVANCE 1 & 2 are Phase 3 RCTs evaluating the efficacy and safety of icotrokinra compared with placebo and deucravacitinib

in participants with moderate-to-severe plaque PsO with PASI 90 and IGA score of 0/1 with at least a 2-grade improvement as co-primary

ICONIC-ASCEND is a Phase 3 RCT and the first-ever head-to-head study seeking to demonstrate the superiority of an oral pill, icotrokinra,

compared to an injectable biologic, ustekinumab in moderate-to-severe plaque PsO.

the ICONIC Clinical Development Program

The pivotal Phase 3 ICONIC clinical development

program of icotrokinra (JNJ-2113) in adult and adolescent individuals with moderate-to-severe plaque PsO was initiated with two studies

in Q4 2023 - ICONIC-LEAD and ICONIC-TOTAL - pursuant to the license and collaboration agreement between Protagonist Therapeutics, Inc.

and Janssen Biotech, Inc., a Johnson & Johson company.vi

The ICONIC clinical development program is being conducted by Johnson and Johnson.

(NCT06095115) is a randomized controlled trial (RCT) to evaluate the efficacy and safety of icotrokinra compared with placebo

in participants with moderate-to-severe plaque PsO, with PASI 90 and IGA score of 0 or 1 with at least a 2-grade improvement as co-primary

(NCT06095102) is a RCT to evaluate the efficacy and safety of icotrokinra compared with placebo for the treatment of PsO

in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or hands and feet) with overall IGA

score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.viii

Phase 3 studies in the development program include ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604),

which are evaluating the efficacy and safety of icotrokinra compared with both placebo and deucravacitinib in adults with moderate-to-severe

plaque PsO.ix,x ICONIC-ASCEND

will evaluate the efficacy and safety of icotrokinra compared with placebo and ustekinumab in participants with moderate-to-severe plaque

psoriasis. ICONIC-PsA 2 (NCT06807424) will evaluate the efficacy and safety of icotrokinra compared to placebo in participants

with active psoriatic arthritis.

Plaque psoriasis (PsO) is a chronic immune-mediated

disease resulting in overproduction of skin cells, which causes inflamed, scaly plaques that may be itchy or painful.xi

It is estimated that 8 million Americans and more than 125 million people worldwide live with the disease.xii

Nearly one-quarter of all people with plaque PsO have cases that are considered moderate to severe. xi On Caucasian

skin, plaques typically appear as raised, red patches covered with a silvery white buildup of dead skin cells or scale.xiii

On skin of color, the plaques may appear darker and thicker and more of a purple, gray or dark brown color.xii

Plaques can appear anywhere on the body, although they most often appear on the scalp, knees, elbows and torso.xii Living

with plaque PsO can be a challenge and impact life beyond a person's physical health, including emotional health, relationships,

and handling the stressors of life.xiv Psoriasis

on highly visible areas of the body or sensitive skin, such as the scalp, hands, feet, and genitals, can have an increased negative impact

on quality of life.xii,xv

Icotrokinra (JNJ-77242113, JNJ-2113)

Investigational icotrokinra is the first targeted

oral peptide designed to selectively block the IL-23 receptor.xvi

The IL-23 pathway underpins the inflammatory response in moderate-to-severe plaque psoriasis (PsO), ulcerative colitis (UC)

and other diseases.xvii,xviii Icotrokinra

binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in

human T cells.xix The license and collaboration

agreement established between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc., a Johnson & Johnson company,

in 2017 enabled the companies to work together to discover and develop next-generation compounds that ultimately led to icotrokinra.xx

Icotrokinra was jointly discovered and is being developed pursuant

to the license and collaboration agreement between Protagonist and Johnson & Johnson. Johnson & Johnson retains exclusive

worldwide rights to develop icotrokinra in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research

conducted pursuant to the agreement against a broad range of indications.xxi,xxii,xxiii

Icotrokinra is being studied in the pivotal Phase 3 ICONIC clinical

development program in moderate-to-severe plaque PsO and active psoriatic arthritis and the Phase 2b ANTHEM-UC study in moderately to

Protagonist Therapeutics is a discovery through

late-stage development biopharmaceutical company. Two novel peptides, icotrokinra and rusfertide, derived from Protagonist's proprietary

discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA expected

in 2025. Icotrokinra (JNJ-2113) is a first-in-class investigational targeted oral peptide that selectively blocks the Interleukin-23

receptor ("IL-23R") which is licensed to Johnson & Johnson Innovative Medicines ("JNJ"), formerly Janssen

Biotech, Inc. Following icotrokinra's joint discovery by Protagonist and JNJ scientists pursuant to the companies' IL-23R

collaboration, Protagonist was primarily responsible for development of icotrokinra through Phase 1, with JNJ assuming responsibility

for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for

the rare blood disorder polycythemia vera (PV). Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals

pursuant to a worldwide collaboration and license agreement entered into in 2024, under which the Company remains primarily responsible

for development through NDA filing. The Company also has a number of pre-clinical stage oral drug discovery programs addressing clinically

and commercially validated targets, including the IL-17 oral peptide antagonist PN-881, an oral hepcidin program, and an oral obesity

information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at www.protagonist-inc.com.

Cautionary Note on Forward-Looking Statements