A Phase 2, Multi-Center, Open-Label Study of Cinrebafusp Alfa (PRS-343) in Combination With Ramucirumab and Paclitaxel in Patients With HER2-Positive Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and in Combination With Tucatinib in Patients With HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

A Phase 2, multi-center, open-label study of cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel in patients with HER2-high and in combination with tucatanib in patients with HER2-low gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Start Date01 Nov 2021

Sponsor / Collaborator

Pieris Pharmaceuticals, Inc.

NCT03330561

/ CompletedPhase 1

A Phase 1, Open-Label, Dose Escalation Study of PRS-343 in Patients With HER2-Positive Advanced or Metastatic Solid Tumors

A multi center, open-label, Phase 1 dose escalation study with expansion cohort is designed to determine the MTD, RP2D and dosing schedule of PRS-343 in patients with HER2+ advanced or metastatic solid tumors.

Start Date13 Sep 2017

Sponsor / Collaborator

Pieris Pharmaceuticals, Inc.

100 Clinical Results associated with Cinrebafusp alfa

100 Translational Medicine associated with Cinrebafusp alfa

100 Patents (Medical) associated with Cinrebafusp alfa

Literatures (Medical) associated with Cinrebafusp alfa

17 Jan 2025·CLINICAL CANCER RESEARCH

A First-in-Human Study of Cinrebafusp Alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies

Article

Author: Pohlmann, Paula ; Aviano, Kayti ; Zettl, Markus ; Shroff, Rachna ; Hahn, Noah ; Liu, Stephen V. ; Hasenkamp, Laura-Carolin ; Hurvitz, Sara ; Ku, Geoffrey ; Duerr, Manuela ; Hamilton, Erika ; Hansbauer, Eva-Maria ; Patnaik, Amita ; Kumar, Raman ; Piha-Paul, Sarina ; Bruns, Ingmar ; Tolcher, Anthony ; Matis, Louis ; Krishnamurthy, Anuradha ; Wurzenberger, Cornelia ; Olwill, Shane A.

Abstract:

Purpose::

4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, NK cells, and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies.

Patients and Methods::

This was a multicenter dose-escalation study involving patients with HER2-positive malignancies who received prior treatment. The study assessed the safety and efficacy of cinrebafusp alfa across various dose levels. Patients were assigned to different cohorts, and antitumor responses were evaluated. The study aimed to determine the MTD and to observe any clinical activity at different dose levels.

Results::

Of 40 evaluable patients in the “active dose” efficacy cohorts, five showed an antitumor response, resulting in an overall response rate of 12.5% and a disease-control rate of 52.5%. Clinical activity was observed at the 8 and 18 mg/kg dose levels, with confirmed objective response rates of 28.6% and 25.0%, respectively. Cinrebafusp alfa was safe and tolerable, with grade ≤2 infusion-related reactions being the most frequent treatment-related adverse event. MTD was not reached during the study.

Conclusions::

Cinrebafusp alfa demonstrates promising activity in patients with HER2-positive malignancies who have progressed on prior HER2-targeting regimens. Its acceptable safety profile suggests it could be a treatment option for patients not responding to existing HER2-directed therapies.See related commentary by Eguren-Santamaría et al., p. 231

01 Oct 2019·Clinical cancer research : an official journal of the American Association for Cancer ResearchQ1 · MEDICINE

Tumor-Localized Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific Antibody-Anticalin Fusion PRS-343

Q1 · MEDICINE

Article

Author: Schlosser, Corinna ; Moebius, Ulrich ; Hinner, Marlon J. ; Rothe, Christine ; Allersdorfer, Andrea ; Berger, Sven ; Matis, Louis ; Matschiner, Gabriele ; Schüler, Julia ; Jaquin, Thomas J. ; Olwill, Shane Anthony ; Wiedenmann, Alexander ; Dürr, Manuela Carola ; Aiba, Rachida Siham Bel

Abstract:

Purpose::

4-1BB (CD137) is a key costimulatory immunoreceptor and promising therapeutic target in cancer. To overcome limitations of current 4-1BB–targeting antibodies, we have developed PRS-343, a 4-1BB/HER2 bispecific molecule. PRS-343 is designed to facilitate T-cell costimulation by tumor-localized, HER2-dependent 4-1BB clustering and activation.

Experimental Design::

PRS-343 was generated by the genetic fusion of 4-1BB–specific Anticalin proteins to a variant of trastuzumab with an engineered IgG4 isotype. Its activity was characterized using a panel of in vitro assays and humanized mouse models. The safety was assessed using ex vivo human cell assays and a toxicity study in cynomolgus monkeys.

Results::

PRS-343 targets 4-1BB and HER2 with high affinity and binds both targets simultaneously. 4-1BB–expressing T cells are efficiently costimulated when incubated with PRS-343 in the presence of cancer cells expressing HER2, as evidenced by increased production of proinflammatory cytokines (IL2, GM-CSF, TNFα, and IFNγ). In a humanized mouse model engrafted with HER2-positive SK-OV-3 tumor cells and human peripheral blood mononuclear cells, PRS-343 leads to tumor growth inhibition and a dose-dependent increase of tumor-infiltrating lymphocytes. In IND-enabling studies, PRS-343 was found to be well tolerated, with no overt toxicity and no relevant drug-related toxicologic findings.

Conclusions::

PRS-343 facilitates tumor-localized targeting of T cells by bispecific engagement of HER2 and 4-1BB. This approach has the potential to provide a more localized activation of the immune system with higher efficacy and reduced peripheral toxicity compared with current monospecific approaches. The reported data led to initiation of a phase I clinical trial with this first-in-class molecule.See related commentary by Su et al., p. 5732

01 Jun 2018·BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy

Anticalin® Proteins as Therapeutic Agents in Human Diseases

Review

Author: Rothe, Christine ; Skerra, Arne

Anticalin proteins are an emerging class of clinical-stage biopharmaceuticals with high potential as an alternative to antibodies. Anticalin molecules are generated by combinatorial design from natural lipocalins, which are abundant plasma proteins in humans, and reveal a simple, compact fold dominated by a central β-barrel, supporting four structurally variable loops that form a binding site. Reshaping of this loop region results in Anticalin proteins that can recognize and tightly bind a wide range of medically relevant targets, from small molecules to peptides and proteins, as validated by X-ray structural analysis. Their robust format allows for modification in several ways, both as fusion proteins and by chemical conjugation, for example, to tune plasma half-life. Antagonistic Anticalin therapeutics have been developed for systemic administration (e.g., PRS-080: anti-hepcidin) or pulmonary delivery (e.g. PRS-060/AZD1402: anti-interleukin [IL]-4-Rα). Moreover, Anticalin proteins allow molecular formatting as bi- and even multispecific fusion proteins, especially in combination with antibodies that provide a second specificity. For example, PRS-343, which has recently entered clinical-stage development, combines an agonistic Anticalin targeting the costimulatory receptor 4-1BB with an antibody directed against the cancer antigen human epidermal growth factor receptor 2 (HER2), thus offering a novel treatment option in immuno-oncology.

News (Medical) associated with Cinrebafusp alfa

27 Mar 2024

·www.biospace.com

Pieris Pharmaceuticals Announces Strategy to Maximize Partnered Milestone and Royalty Potential

BOSTON, MA / ACCESSWIRE / March 27, 2024 / Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS) provided a corporate update today announcing a strategy to maximize its ability to capture the potential milestones from its 4-1BB bispecific Mabcalin® (antibody-Anticalin fusion) protein immuno-oncology assets partnered with Pfizer (formerly Seagen), Boston Pharmaceuticals, and Servier. After considering an extensive range of options, the Company's Board of Directors decided to implement this new strategy along with relevant cost-saving measures that are expected to extend the Company's cash runway into 2027. The Company's strategic review process has focused on maximizing stockholder value, which includes the preservation of potential milestone and royalty payments the Company is eligible to receive. Management and the Board of Directors evaluated a broad spectrum of potential options, including asset in-licensing, out-licensing, royalty monetization, strategic transactions (including reverse mergers, strategic mergers, and sale), and liquidation. With the assistance of the Company's retained strategic advisor, Stifel, Nicolaus & Company, more than 500 companies were contacted regarding a strategic transaction, and the Company underwent a robust process to identify and negotiate with a select number of final candidates. The Company entered into extended exclusivity with one party contemplating a strategic merger, which centered on that party's interest in developing the Company's clinical-stage asset cinrebafusp alfa, but after extensive diligence and negotiations, that counterparty was unable to secure adequate capitalization and offer acceptable terms. The Company ultimately determined that the Company's planned repositioning offers the best opportunity to maximize stockholder value. "After an extensive review of strategic alternatives, our Board has determined that retaining the value of future milestone and royalty potential, which could result in up to $75 million of milestone payments during the next several years, as well as potential significant downstream milestones and royalty economics is key to maximizing value for our shareholders," said James Geraghty, Chairman of the Board of Directors. "Implementing a lean business model with substantially reduced operating expenses results in an expected cash runway into at least 2027, while offering risk-mitigated diversification with high quality partners. Finally, on behalf of the full board, I want to express our gratitude to our employees for all their contributions and express to our investors our commitment to maximize shareholder value going forward." In support of optimizing potential milestones and royalties, the Company's strategic repositioning includes: A plan to maintain strategic capability by maintaining a lean and experienced Board and management pro actively pursue the Company's strategy and consider strategic options; The discontinuation of all the Company's research and development efforts, which is expected to be completed by the middle of 2024; A workforce reduction that affects additional employees and the executive leadership team, expected to be implemented in the second quarter; A plan to reduce the size of the Company's Board of Directors, to be better aligned with the nature of the Company's continuing operations, also expected to be implemented in the second quarter; "A compelling feature of this new strategy is its planned self-funded nature, offering the opportunity to capture meaningful future milestones and royalties through multiple partnered programs that are fully funded by third parties," commented Stephen Yoder, President and Chief Executive Officer. Mr. Yoder continued, "The new strategy will also facilitate the potential to pursue milestone and royalty monetization agreements with third parties to possibly accelerate cash distributions to shareholders." Since initiating the strategic review in July 2023, the Company implemented several steps, including scaling back operational costs, inclusive of associated headcount reductions, ceasing development of PRS-220 and PRS-400 within its respiratory franchise, and suspending investments associated with co-development of partnered assets. The Company has also eliminated its material long-term obligations through the previously disclosed termination of its lease obligation in Germany, while simultaneously continuing to improve its cash position through the sale of its laboratory and office equipment. As previously disclosed, the Company remains eligible to receive contingent milestone and royalty payments across its partnered 4-1BB bispecific Mabcalin protein franchise resulting from its partnerships with Pfizer, Boston Pharmaceuticals, and Servier. More specifically: All partnered programs are fully funded by the respective partner, and there are no further discovery or development obligations for the Company; The Company may be entitled to aggregate milestones of up to $20 million upon first patient dosed in the phase 2 trials for SGN-BB228, S095012 (formerly PRS-344) and BOS-342, which are all currently in phase 1 clinical development; The Company may be entitled to aggregate milestones of up to $55 million upon first patient dosed in pivotal clinical trials for SGN-BB228, S095012 (formerly PRS-344) and BOS-342; Two additional discovery programs with Pfizer that would entitle the company to additional milestones if brought forward into IND-enabling activities; Total development milestone potential from the three clinical stage assets in single, primary indications could be up to $275 million. Total commercial milestone potential on the same assets, if they are approved, could amount to more than $500 million. A potential additional aggregate amount of up to $160 million in both developmental and commercial milestones exists if these programs are developed in additional indications; and In addition to the milestone potential, all programs are eligible for royalties from commercial sales ranging from mid-single digits to low double digits. In addition to alliance management activities for the partnered programs above, the Company remains committed to trying to obtain value for its products in prior development, including cinrebafusp alfa, as well as proprietary platform capabilities by pursuing potential out-licensing or sale transactions. In addition to pursuing possible monetization of the projected royalty and milestone payments at attractive valuations, the Company may also, from time-to-time, opportunistically consider other options that it believes may increase stockholder value. We can provide no assurance that the Company will receive any potential milestone or royalty payments or on the timing of any such milestone or royalty payments that may become due, or that any potential strategic transactions will occur. As of December 31, 2023, the Company had $26.4 million in cash and investments. The Company does not expect to have any future financing requirements to achieve the near-term milestone potential of its partnered programs. The Company may consider cash dividends as and when milestone or other payments are received if the Company determines there is sufficient cash and investments to achieve the Company's near and long-term objectives. About Pieris Pharmaceuticals: Pieris is a biotechnology company based in Boston, Massachusetts that could potentially be entitled to receive development, regulatory, and sales-based milestones from its 4-1BB bispecifics immuno-oncology assets partnered with Pfizer (formerly Seagen), Boston Pharmaceuticals, and Servier. In addition to the milestone potential, Pieris would be eligible for sales royalties on the same partnered programs if they ultimately are approved for commercialization. The Company is seeking potential acquirers for its remaining preclinical and clinical assets. For more information, visit . Forward-Looking Statements: This press release 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 press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things statement relating to, our expected cash runway and our belief that the Company's strategy is fully funded; any potential future cash dividend; statements relating to the strategy being self-funded; statements relating to potentially considering strategic opportunities; anticipated timing, achievement, and receipt of milestone and/or royalty payments provided for in our collaboration agreements; the potential size of potential milestones and royalties; the timing, impact, and extent of reductions in our workforce and the size of our Board of Directors; the cost-saving potential of our strategic reprioritization and restructuring; the potential for us to out-license or sell our products in prior development, including cinrebafusp alfa, and our proprietary platform capabilities; and the possible monetization of milestone and royalties. Actual results could differ from those projected in any forward-looking statement due to numerous factors. Such factors include, among others, expectations for achievement of contractual milestones; availability of funding sufficient for the Company's foreseeable and unforeseeable operating expenses; our cash runway may be reduced by unanticipated liabilities or decisions to opportunistically pursue strategic opportunities; our ability to be successful in exploring and consummating one or more licensing or other transactions on attractive terms if at all for our proprietary platform capabilities or our products in prior development; our ability to maintain a lean and capable management team and board over time; our actual reductions in spending as compared to anticipated cost reductions; including in collaboration with other parties, the inherent uncertainties associated with developing new products or technologies, such as Anticalin based compounds, our partners' ability to develop, complete clinical trials for, obtain approvals for and commercialize any of our partnered product candidates; our partners ability to achieve expected market share if the drugs are approved and commercialized; uncertainty of overall market size of any of our partnered product candidates; competition in the industry in which we operate; the possibility that our partners may decide not to prioritize or further pursue the programs that we hope to receive milestone and royalty payments under; the fact that data and results from clinical studies may not necessarily be indicative of future results; we may face challenges in continuing to comply with Nasdaq listing standards, such as those relating to minimum price and operating company status; delays or disruptions due to geopolitical issues, including the conflict in Ukraine and the Middle East; and overall 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 the Securities and Exchange Commission, or the SEC, available at including, without limitation, the Company's most recent Annual Report on Form 10-K, the Company's Quarterly Reports on Form 10-Q, and subsequent filings with the SEC. Investor Relations Contact: Pieris Pharmaceuticals, Inc. Investors@pieris.com SOURCE: Pieris Pharmaceuticals, Inc. View the original press release on accesswire.com

Phase 1

18 Jul 2023

·www.fiercebiotech.com

AstraZeneca bails on failed Pieris asthma asset, forcing the biotech to restructure, lay off 70% of staff

Pieris is on the hunt for new collaborations after AstraZeneca stepped away from a partnered asthma med. AstraZeneca has sailed away from a licensing deal for Pieris Pharmaceuticals’ asthma med, forcing the biotech to begin charting a new corporate course and lay off 70% of its staff in the process. The Boston-based company said Tuesday that AstraZeneca has terminated the partnership for elarekibep, a month after the Big Pharma stopped dosing of a trial following concerning nonclinical toxicology data. Pieris said today that AstraZeneca has also stepped away from “the remaining discovery program.” AstraZeneca’s decision has thrust Pieris into deep water without a life preserve, with the biotech shedding 70% of staff to stay afloat. The Big Pharma originally handed over $45 million in 2017 to partner up on the then-preclinical elarekibep. Pieris, armed with $54.9 million in cash as of the end of June, was blunt in its assessment of future moves, saying explicitly that it’s on the hunt for new partnerships for its existing pipeline. That includes PRS-220, a phase 1 inhaled Anticalin protein targeting connective tissue growth factor to treat idiopathic pulmonary fibrosis. But that trial appears to have stalled, with no update made to the clinical trial record since November 2022 even though the primary completion date was earlier in June. The company hoped to enroll 64 patients in the single and multiple ascending dose study. The biotech said it’s also looking to partner out its bispecific protein cinrebafusp alfa and PRS-400, another respiratory med aimed at muco-obstructive lung diseases. Should Pieris successfully find partners, that would leave it with little-to-no wholly-owned programs in its pipeline. The end result may ultimately be a larger transaction than just one or two new partnerships. Pieris says it’s looking at all options, including an acquisition or merger. The company’s share price, already in the basement, ticked up marginally on today's announcement. It’s a disappointing update for a company that had accrued significant validation through licensing deals, namely for its immuno-oncology pipeline. Pieris has two ongoing deals with Seagen, including one clinical-stage asset, PRS-346, and another with Servier for phase 1-stage PRS-344. A fourth pact with Boston Pharmaceuticals involves preclinical med PRS-342.

Phase 1License out/inAcquisitionPROTACs

18 Jul 2023

·firstwordpharma.com

Pieris cuts 70% of workforce as AstraZeneca terminates tie-up

Pieris Pharmaceuticals announced on Tuesday that it would cut around 70% of its staff and explore strategic options due to events that have impacted its inhaled respiratory franchise, including AstraZeneca's discontinuation of a Phase IIa study for elarekibep in asthma. The company added that the UK drugmaker has now decided to terminate its agreement for the IL-4 receptor alpha inhibitor, which was signed in 2017, handing back rights to the inhaled Anticalin therapy."We are pursuing strategic options across three main areas," explained CEO Stephen Yoder, adding that "one track is accelerating partnering discussions of PRS-220 and PRS-400," which are inhaled Anticalin proteins in preclinical trials for respiratory diseases. The company is also focused on selecting a development partner and deal structure to re-initiate clinical development of its former lead immuno-oncology asset cinrebafusp alfa.The drug, also known as PRS-343, has shown potential in a HER2+ gastric cancer trial, but "was discontinued for strategic reasons" last year. Yoder added "third, we will explore whether our balance sheet, position as a public company, and other assets are of strategic value to a range of third parties."Pieris currently has cash, cash equivalents and investments totalling $54.9 million, with the workforce cuts set to reduce cash spending. The company noted that it does not intend to make any further disclosures regarding the strategic review process until a specific course of action has been decided.

Phase 2Clinical Trial Failure

100 Deals associated with Cinrebafusp alfa

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
HER2 positive Gastroesophageal Junction Adenocarcinoma	Phase 2	United States	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2 positive Gastroesophageal Junction Adenocarcinoma	Phase 2	South Korea	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2-expressing Gastric Adenocarcinoma	Phase 2	United States	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2-expressing Gastric Adenocarcinoma	Phase 2	South Korea	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2-Low Gastric Cancer	Phase 2	United States	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2-Low Gastric Cancer	Phase 2	South Korea	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2-Low Gastroesophageal Junction Cancer	Phase 2	United States	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2-Low Gastroesophageal Junction Cancer	Phase 2	South Korea	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2-positive gastric cancer	Phase 2	United States	Pieris Pharmaceuticals, Inc.	01 Nov 2021
HER2-positive gastric cancer	Phase 2	South Korea	Pieris Pharmaceuticals, Inc.	01 Nov 2021

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AACR2023 Manual	Phase 2	HER2 positive Gastroesophageal Junction Adenocarcinoma Second line HER2 Positive	5	Cinrebafusp alfa+Ramucirumab+Paclitaxel	vblgblqrme(bcrdcogsav) = The most frequent treatment emergent adverse events (TEAEs) included Grade 1/2 fatigue (4 patients) and Grade 1-3 diarrhea (4 patients). hroqgympzb (kzwvnqoqjd )	Positive	14 Apr 2023
NCT03330561 (ESMO2020) Manual	Phase 1	HER2 Positive Cancer HER2 Positive	70	Cinrebafusp alfa	pejvjaasdr(clkprynkbo) = none fphperylen (dpqmcjupgu ) View more	Positive	20 Sep 2020
NCT03330561 (O82, SITC2020)	Phase 1	HER2 Positive Cancer	51	PRS-343 0.0005 mg/kg	tgaqifavml(hqutdkcvcy) = jfpraflkhn tfsbhqejbg (msmzlofkts )	Positive	15 Apr 2020

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Hiro LS Researcher

The AI Search Engine Built to Accelerate Biopharma Decisions

Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.

Ask any biopharma research question→

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, Patsnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Discover Synapse Data Servers

Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis