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Pieris Pharmaceuticals Presents Updated Phase 1 Monotherapy Data for 4-1BB/HER2 Bispecific Cinrebafusp Alfa and Preclinical Data for 4-1BB/PD-L1 Bispecific PRS-344/S095012 at 2021 AACR Annual Meeting

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  • Additional, ongoing confirmed durable partial response and three additional patients with stable disease as best response at the highest dose cohort of cinrebafusp alfa
  • Durable anti-tumor activity in heavily pre-treated patient population ​including "cold" and HER2-low expressing tumors
  • Dose-dependent immune activation and 4-1BB modulation in both HER2-high and HER2-low expressing patients
  • PRS-344/S095012 preclinical data show that the drug candidate induces a dose-dependent anti-tumor response in an anti-PD-L1-resistant mouse model

BOSTON, MA / ACCESSWIRE / April 10, 2021 / Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin® technology platform for respiratory diseases, cancer, and other indications, today presented a clinical data update from the phase 1 monotherapy study of cinrebafusp alfa (PRS-343), a 4-1BB/HER2 bispecific for the treatment of HER2-expressing solid tumors, in an oral presentation at the American Association for Cancer Research (AACR) Virtual Congress 2021. The Company also presented preclinical data for PRS-344/S095012, a 4-1BB/PD-L1 bispecific the Company is developing with Servier, at a poster session at the congress.

Cinrebafusp Alfa (PRS-343):

Presented data demonstrated additional clinical benefit at the highest dose, including an additional, ongoing confirmed durable partial response, three additional patients with stable disease as best response, and overall durable benefit. Based on clinical benefit and pharmacodynamic correlates, cinrebafusp alfa showed a clear dose response and a 4-1BB-driven mechanism of action. Additionally, clinical benefit was observed in patients with "cold" tumors as well as those with HER2-low expressing tumors. Cinrebafusp alfa continues to be well-tolerated. The Company plans to initiate a phase 2 study in gastric cancer this summer that will evaluate both HER2-high and HER2-low patient settings.

As of the cut-off date of February 25, 2021, 8 patients in the monotherapy trial were evaluable for a response at the highest dose cohort (cohort 13b; 18 mg/kg Q2W) out of a total of 42 response-evaluable patients enrolled in the predicted active dose cohorts (cohort 9 and higher; ≥2.5 mg/kg) in the study.

  • In cohort 13b, one additional patient (cancer of unknown primary) achieved an ongoing confirmed durable partial response, for an updated overall response rate (ORR) of 25% in that cohort as compared to an ORR of 12% across active dose levels.
  • In cohort 13b, three additional patients experienced stable disease as best response, for an updated disease control rate (DCR) of 63% in that cohort as compared to a DCR of 52% across active dose levels.
  • Cinrebafusp alfa activates adaptive and innate immunity in the tumor microenvironment, consistent with intended mode of action as evidenced by post-treatment increases in CD8+ T cells, NK cells and cytotoxic activity.
  • Dose-dependent increases of CD8+ T cells in the tumor and soluble 4-1BB in the blood of patients demonstrate target engagement and a 4-1BB-driven mode of action.
  • Cinrebafusp alfa shows preliminary evidence of activity among "cold" tumor types as well as "hot" tumor types.
  • Activity in HER2-low expressing patients supports continued development of cinrebafusp alfa in that population, which the Company will evaluate in its phase 2 gastric cancer study.
  • Cinrebafusp alfa monotherapy appeared to be well-tolerated up to 18 mg/kg, with no significant specific anti-HER2 or anti-4-1BB safety signal and no dose limiting toxicity identified.

The cinrebafusp alfa data presented at AACR can be found in an updated corporate presentation at https://ir.pieris.com.

PRS-344S095012:

The synergistic preclinical data presented for PRS-344/S095012 demonstrate PRS-344/S095012 is superior to the combination of PD-L1- and 4-1BB-targeting molecules. In an anti-PD-L1-resistant mouse model, the drug candidate induces a dose-dependent anti-tumor response and significantly extends survival. In vitro, PRS-344/S095012 enhances effective CD8+ T cell response and proinflammatory cytokine release.

PRS-344/S095012-mediated 4-1BB activation is strictly PD-L1 dependent, reducing the risk of peripheral toxicity. Furthermore, 4-1BB co-stimulation only occurs in combination with simultaneous TCR signaling, restricting its activity to antigen-specific T cells. PRS-344/S095012 also displays mAb-like pharmacokinetics in mice.

These data support further development of PRS-344/S095012, for which the phase 1 study is expected to begin this year.

A copy of the poster is available at this link.

"The matured data from the highest dose cohort of cinrebafusp alfa demonstrate a clear dose-dependent response that supports our recommended phase 2 dose, and the biomarker data generated across all active dose cohorts demonstrate that cinrebafusp alfa activity is 4-1BB-driven and that the drug candidate is active not only in HER2-high expressing tumors, but also HER2-low expressing tumors - a significant opportunity and unmet medical need that we are excited to pursue in our upcoming phase 2 study," said Stephen S. Yoder, President and Chief Executive Officer of Pieris. "Separately, we are pleased with the clear evidence of dose-dependent synergistic anti-tumor effects of PRS-344/S095012, as well as further evidence for its tumor-localized mechanism of action, and we look forward to moving this asset into the clinic this year. By its design, this bispecific has best-in-class potential in the 4-1BB/PD-L1 arena."

About Cinrebafusp Alfa:

Cinrebafusp alfa (PRS-343) is a 4-1BB/HER2 fusion protein comprising a 4-1BB-targeting Anticalin protein and a HER2-targeting antibody. The drug candidate is currently in development for the treatment of HER2-positive solid tumors. Based on encouraging phase 1 study results, which demonstrated clinical benefit as single agent and biomarker data indicative of a 4-1BB-driven mechanism of action, the Company is actively working towards initiating a phase 2 study of cinrebafusp alfa in combination with ramucirumab and paclitaxel for the treatment of HER2-high expressing gastric cancer and in combination with tucatinib in HER2-low expressing gastric cancer.

About Pieris Pharmaceuticals:

Pieris is a clinical-stage biotechnology company that discovers and develops Anticalin protein-based drugs to target validated disease pathways in a unique and transformative way. Our pipeline includes inhalable Anticalin proteins to treat respiratory diseases and immuno-oncology multi-specifics tailored for the tumor microenvironment. Proprietary to Pieris, Anticalin proteins are a novel class of therapeutics validated in the clinic and by partnerships with leading pharmaceutical companies. Anticalin® is a registered trademark of Pieris. For more information, visit www.pieris.com.

Forward Looking Statement:

This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, whether data from patients enrolled to date will be sufficient to inform the recommended phase 2 dose for the Company's planned proof of concept study of cinrebafusp alfa in gastric cancer; 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 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, and PRS-352 and the expected timing of the initiation of the next stage of cinrebafusp alfa's development in gastric cancer. 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; competition in the industry in which we operate; delays or disruptions due to COVID-19; and market conditions. These forward-looking statements are made as of the date of this press release, 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 SEC available at www.sec.gov, including without limitation the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2020 and the Company's Quarterly Reports on Form 10-Q.

Investor Relations Contact:

Pieris Pharmaceuticals, Inc.
Maria Kelman
Executive Director, Investor Relations
+1 857 362 9635
kelman@pieris.com

SOURCE: Pieris Pharmaceuticals, Inc.



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