May 25, 2022 7:58 AM EDT

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Forward-Looking Statements This presentation contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Statements in this presentation that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, the timing for initiation of clinical trials of PRS-220; whether PRS-220 will provide a clinical benefit in the treatment of IPF and PASC-related fibrosis; whether the combination of cinrebafusp alfa with other therapies could address a high medical need in HER2 gastric cancer patients who do not respond to traditional HER2-targeted therapies; whether the effects of the combination of cinrebafusp alfa with other therapies seen in preclinical studies will be observed in clinical trials; the receipt of royalty payments provided for in our collaboration agreements; the expected timing and potential outcomes of the reporting by the Company of key clinical data from its programs; references to novel technologies and methods and our business and product development plans, including the Company's cash resources, the advancement of our proprietary and co-development programs into and through the clinic and the expected timing for reporting data, making IND filings or achieving other milestones related to our programs, including PRS-060/AZD1402, cinrebafusp alfa, PRS-344/S095012, PRS-352/S095025, PRS-342/BOS-342, and PRS-400; our continued progress in the areas of co-stim bispecifics and inhaled therapeutics; the potential addressable market for our product candidates; and the advancement of our developmental programs generally. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, our ability to raise the additional funding we will need to continue to pursue our business and product development plans; the inherent uncertainties associated with developing new products or technologies and operating as a development stage company; our ability to develop, complete clinical trials for, obtain approvals for and commercialize any of our product candidates, including our ability to recruit and enroll patients in our studies; our ability to address the requests of the U.S. Food and Drug Administration; competition in the industry in which we operate; delays or disruptions due to COVID-19 or geo-political issues, including the conflict in Ukraine; and market conditions. These forward-looking statements are made as of the date of this presentation, and we assume no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Investors should consult all of the information set forth herein and should also refer to the risk factor disclosure set forth in the reports and other documents we file with the Securities and Exchange Commission available at, including without limitation the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2021 and the Company’s subsequent Quarterly Reports on Form 10-Q. 2

Executive Summary 3 • Protein therapeutics that exploit biology validated by mAbs yet are engineered for focused activity at disease locus • Improved activity, reduced side effects, increased convenience Superior Medicines via Efficient Biology • Oral inhaled antagonists for respiratory disease • Locally activated immuno-oncology bispecifics • Four clinical stage assets expected by year-end, with three programs at least half-funded by partners/grant income Two Focus Areas • ~$200M since 2017 in upfronts, milestones and equity investments • Several co-developed and out-licensed programs • Clinical supply for combination studies and development expertise Supportive Partnerships

A Novel Therapeutic Class with Favorable Drug-Like Properties • Human – Derived from lipocalins (human extracellular binding proteins) • Small – Monomeric, monovalent, small size (~18 kDa vs. ~150kDa mAbs) • Stable – Inhalable delivery • Simple – Bi/multispecific constructs • Proprietary – Broad IP position on platform and derived products Translational Science Expertise to Deploy Platform in Meaningful Way • Immunology expertise underpins IO and respiratory focus • A leader in 4-1BB and costim biology • Patient phenotyping efforts for improved stratification and novel intervention points in, e.g., asthma Anticalin® Proteins as Therapeutic Modalities 4 Anticalin Protein Target

Two-fold Focus of Anticalin Platform Deployment Inhalable formulations to treat respiratory diseases locally 5 Bispecifics for local immune agonism to treat cancer Tumor cell Immune cell

Validating Partnerships & Non-Dilutive Capital 6 • PRS-060/AZD1402 (co-dev option) + 3 additional programs • Upfront & milestones to date: $70.5M • Eligible for over $5B in potential milestone payments plus royalties • 3-program IO bispecific partnership • Upfront & milestones to date: $35M • Eligible for $1.2B in potential milestone payments plus royalties • PRS-344/S095012 & PRS-352/S095025 • Upfront & milestones to date: ~$41M • Eligible for ~$230M in potential milestone payments plus royalties • 1 respiratory program + 1 ophthalmology program • Upfront & milestones to date: $20M • Eligible for $1.4B in potential milestone payments plus royalties • Boston Pharmaceuticals holds exclusive license for PRS-342/BOS-342 • Upfront & milestones to date: $10M • Eligible for ~$353M in potential milestone payments and royalties

Efficacy & Safety Inhaled Anticalin Proteins are a Promising Strategy for the Treatment of Respiratory Diseases 7 Pieris Strategy Local, specific, and more efficient targeting of disease-relevant pathways in the lung via inhaled delivery of Anticalin proteins Higher Specificity Local DeliverySystemic Delivery IV or SC Antibodies Oral Small Molecules Inhaled Small Molecules Inhaled Anticalin Proteins Lower Specificity

Respiratory Pipeline 8 Program Target Indication Discovery Preclinical Phase 1 Phase 2 Partner PRS-060/AZD1402* IL4Rα Asthma PRS-220 CTGF IPF, PF-ILD, PASC-PF# AstraZeneca Programs** n.d. n.d. PRS-400 n.d. n.d. Genentech (GENE1) n.d. n.d. #IPF - Idiopathic Pulmonary Fibrosis, PF-ILD - Progressive Fibrosing Interstitial Lung Diseases, PASC-PF - Post-Acute sequelae of SARS-CoV-2 infection (PASC) Pulmonary Fibrosis (PF) ‡~$17 million grant from the Bavarian government to evaluate PRS-220 in PASC-PF covers more than half of early-stage and phase 1 development costs of PRS-220 *Pieris has separate U.S. co-development and co-commercialization options on PRS-060/AZD1402 **Pieris has U.S. co-development options for two of three additional programs partnered with AstraZeneca Phase 2a fully sponsored by AZ >50% grant-funded‡

PRS-060/AZD1402: Inhaled IL-4Rα Antagonist 9 PRS-060/AZD1402Candidate Inhibiting IL4-Rα (disrupts IL-4 & IL-13 signaling)Function/MoA Moderate-to-severe asthmaIndications Phase 2a in moderate uncontrolled asthmaticsDevelopment Co-development and U.S. co-commercialization options, including gross margin shareCommercial Rights PRS-060/AZD1402

PRS-060/AZD1402 Progressed into Efficacy Portion of Phase 2a 10 Participant Population: Moderate asthmatics controlled on ICS/LABA Primary Endpoint: Safety and tolerability compared to placebo from baseline until follow-up (approximately 56 days) # of Participants: ~45 (randomized: 1:1:1 for part 1a; 2:1 for part 1b) Part 1 (Safety) Participant Population: Moderate uncontrolled asthmatics on ICS/LABA with blood EO count of ≥ 150 cells/μL and FeNO ≥ 25 ppb at screening* Primary Endpoint: Improvement of FEV1 at four weeks relative to placebo # of Participants: ~300 (randomized: 1:1:1 for part 2a; 2:1 for part 2b) Part 2 (Efficacy) Study is sponsored, conducted, and funded by AstraZeneca Parts 1b & 2a initiated 1Q 2022 Dry powder formulation, administered b.i.d. over four weeks on top of standard-of-care therapy (medium dose ICS with LABA)  Part 1a: 1mg + 3 mg Dose  Part 1b: 10 mg Dose  Part 2a: 1mg + 3 mg Dose  Part 2b: 10 mg Dose *In addition to uncontrolled asthmatics with threshold EO count and FeNO profile, there are other enrollment criteria associated with part 2 not in part 1, including FEV1, and a different ACQ score.

DPI Formulation of PRS-060/AZD1402 Passed Safety Review Safety review performed of the following (compared to placebo): Incidence of adverse events Changes in laboratory markers (immune biomarkers, clinical chemistry, and hematology) Forced expiratory volume in 1 second (FEV1) Pharmacokinetics Safety review successfully completed for two dose levels (part 1a), triggering efficacy study (part 2a) in participants with asthma uncontrolled on medium dose ICS-LABA 31 moderate asthmatics controlled on standard-of-care therapy (medium dose ICS with LABA) were dosed twice daily over four weeks randomized across two dose levels and placebo (1:1:1) 11

Co-Development Options for PRS-060/AZD1402 PIRS Opt-in Decision Point Phase 2a Primary Endpoint: Improvement of FEV1 at 4 weeks relative to placebo Co-Dev Option Requirements: 30-day opt-in period triggered upon both completion of Phase 2a trial and notice by AZ (must include product development plan & budget) • 25% cost share with cost cap • Single digit up to high-teen royalties for product lifetime • Development milestones approximating 50% of development costs • Potential $3.5B+ in sales milestones • No opt-in & no cost sharing • Single digit up to mid-teen royalties for royalty term • Same development milestones as 25% option; up to $1.9B in sales milestones • 50% cost share without cost cap • Gross margin share percentage in mid-twenties for the product lifetime • Development milestones approximating two-thirds of 25% option Three Possible Options 12

PRS-220: Inhaled CTGF Antagonist PRS-220Candidate Inhibiting CTGF/CCN2Function/MoA IPF and PASC-PF*Indications Entering phase 1 in healthy subjects this year Development Fully proprietaryCommercial Rights PRS-220 *Idiopathic pulmonary fibrosis (IPF) and post-acute sequelae of SARS-CoV-2 infection pulmonary fibrosis (PASC‐PF) 13

IPF: High Unmet Medical Need and Significant Commercial Opportunity people affected worldwide with increasing global incidence, with ~130K affected in the US each year1,2 3 to 5 million mean survival from the time of diagnosis2 2 to 5 years current market in sales>$3B 14 1 – Glassberg, American Journal of Managed Care, 2019 2 – Meltzer & Noble, Orphanet Journal of Rare Diseases, 2008 Martinez, Nature Rev Dis Primer, 2017 IPF is a chronic, progressive, and ultimately fatal lung disease of unknown cause characterized by chronic lung inflammation and progressive scarring (fibrosis) of the tissues between the alveoli of the lung Currently approved treatments provide modest benefit, in addition to having side effects that require management

PRS-220: Inhaled Solution The only CTGF inhibitor in clinical trials for IPF is a monoclonal antibody administered by IV infusion, 30 mg/kg every three weeks The objective of PRS-220 is to more efficiently engage a clinically validated target via oral inhalation directly to the lung epithelium and interstitium Benefits of inhaled administration: • Inhaled administration eliminates the need for additional clinic visits required for systemic drug administration • Direct administration into the lungs may result in more efficient CTGF inhibition in the site of the disease • Patients with IPF frequently take inhaled medications and thus no additional training required • This approach supports add-on to SOC, whereas patients on SOC are excluded from current studies of reference mAb CTGF has been clinically validated with a systemically administered mAb but leaves significant room for improvement and differentiation 15

High-value target 4-1BB & the Advantages of Anticalin-based Bispecifics • Drives meaningful clinical benefit through proliferative, killing and durability impact on tumor-specific T cells • Improves metabolic fitness for increased survival of T cells • Bispecifics designed to efficiently activate 4-1BB on tumor- specific T cells, avoiding hepatic toxicity • Lead program is safe, well-tolerated and has single-agent activity in heavily pre-treated patients • Several 4-1BB-based follow-on programs Local activation solution 16 • Despite activity, inefficient mAb approaches have led to systemic 4-1BB activation, resulting in hepatic toxicity Historical challenges of systemic mAbs

Immuno-Oncology Pipeline 17 Program Target Indication Discovery Preclinical Phase 1 Phase 2 Partner Cinrebafusp Alfa (PRS-343) 4-1BB/HER2 HER2-High GC* HER2-Low GC** PRS-344/ S095012 4-1BB/PD-L1 n.d. PRS-352/ S095025 OX40/PD-L1 n.d. PRS-342/ BOS-342 4-1BB/GPC3 n.d. Seagen Programs‡ Co-stim Agonist n.d. Ramucirumab supplied by Eli Lilly Tucatinib supplied by Seagen ‡3 bispecific programs in collaboration with Seagen, with Pieris retaining a US co-promotion option for one of the three programs * Phase 2 study includes Cinrebafusp Alfa in combination with ramucirumab and paclitaxel (HER2-high arm) **Phase 2 study includes Cinrebafusp Alfa in combination with tucatinib (HER2-low arm) ~50% costs covered Out-licensed

Cinrebafusp Alfa (PRS-343): Lead IO Asset 18 Cinrebafusp alfa (PRS-343)Candidate Tumor-targeted 4-1BB agonism and HER2 antagonismFunction/MoA HER2-high and HER2-low gastric cancerIndications Phase 2Development Fully proprietaryCommercial Rights HER2-Targeting Antibody 4-1BB-Targeting Anticalin Proteins

Cinrebafusp Alfa Phase 1 Summary Acceptable profile observed at all doses tested with no dose-limiting toxicities Clinical benefit at active dose levels (≥ 2.5 mg/kg), including confirmed complete response and several confirmed partial responses Dose-dependent immune activation and 4-1BB modulation in both HER2-high and HER2-low expressing patients Durable anti-tumor activity in heavily pre-treated patient population, including "cold" tumors As lead IO program, cinrebafusp alfa provides key validation of 4-1BB franchise, including PRS-344/S095012 and PRS-342/BOS-342 19

Cinrebafusp Alfa Clinical Development Plan 20 Go/No-Go Analysis Gastric Cancer 2L A R M A A R M A HER2-High (IHC3+ or IHC2+/ISH+) Cinrebafusp Alfa + Ramucirumab + PaclitaxelA R M A Phase 2 Details add. 20 – 40 pts add. 20 – 40 pts Part BPart A N = ~ 20 pts Target ORR ≥ 50% N = ~ 20 pts Target ORR ≥ 40% Gastric Cancer 2L+ A R M B A R M B HER2-Low (IHC2+/ISH- or IHC1+) Cinrebafusp Alfa + TucatinibA R M B Phase 2 Dose: Two-cycle loading dose of 18 mg/kg (Q2W), followed by an 8 mg/kg dose (Q2W) in subsequent cycles High bar to progress to Part B based on ORR, durability, and safety

PRS-344/S095012: Meaningfully Building on Localized MoA of Cinrebafusp Alfa 21 PRS-344/S095012Candidate Localized 4-1BB agonism with PD-L1 antagonismFunction/MoA N.D.Indications Phase 1 (in co-dev with Servier)Development Co-development with full U.S. commercial rights; royalty on ex-U.S. salesCommercial Rights PD-L1-Targeting Antibody 4-1BB-Targeting Anticalin Proteins

Financial Overview (as of 3/31/22) 22 non-dilutive capital from partnerships since 2017>$175M $100.3M Cash, Cash Equivalents & Investments $0.00 Debt 74.1M CSO grant announced in 2021>$17M~$17M1 1Calculated based on the June 25, 2021, noon buying rate of €1.00 to U.S. $1.1938

255 State Street Boston, MA 02109 USA Zeppelinstraße 3 85399 Hallbergmoos Germany Nasdaq: PIRS SUPERIOR MEDICINES THROUGH EFFICIENT BIOLOGY IR: [email protected] BD: [email protected]


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