PRS-344 / Palvella Therapeutics - LARVOL DELTA

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=45 | Completed | Sponsor: Servier Bio-Innovation LLC | Active, not recruiting ➔ Completed | Trial completion date: Apr 2026 ➔ Apr 2025 | Trial primary completion date: Jul 2025 ➔ Apr 2025

Trial completion • Trial completion date • Trial primary completion date • Solid Tumor

Pharmacodynamic characterization of PRS-344/S095012, a PD-L1x4-1BB antibody-Anticalin fusion protein (Mabcalin), in a dose escalation study in patients with advanced solid tumors (AACR 2025) - P1/2 | "A cohort of 12 patients at the 36mg dose level was pre-treated with Obinutuzumab (OBI) to mitigate anti-drug antibody (ADAs) formation. Plasma and PBMCs were collected pre-dose (Cycle 1 Day 1), and on-treatment (during cycle 1) to measure cytokine levels, Soluble 4-1BB (s4-1BB) as a surrogate for target engagement, and immune cell activation by flow cytometry... S095012 elicited a robust, dose-dependent enhancement of immune cell activation, which was further amplified by OBI pre-treatment, increasing the incidence of irAEs. A target with more specific tumor expression than PD-L1 might be better suited for selective 4-1BB agonism to minimize immune toxicities related to systemic immune cell activation."

Clinical • IO biomarker • Metastases • PK/PD data • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL10 • TNFA

Results of a phase 1 first-in-human study of PRS-344/S095012, a PD-L1x4-1BB antibody-Anticalin fusion protein (Mabcalin), in patients with previously treated advanced solid tumors (AACR 2025) - P1/2 | "One cohort of patients received pretreatment with the anti-CD20 mAB obinutuzumab (OBI) to prevent the development of anti-drug antibodies (ADAs). As of November 18, 2024, n=45 patients had received PRS-344/S095012 at dose levels of 12mg (n=4), 36mg (n=21, with 12 patients pretreated with OBI), 60 mg (n=14) and 80 mg (n=6) IV Q2W. PRS-344/S095012 was associated with significant toxicity that was inconsistent with the aim of improving the therapeutic index of activating 4-1BB. While OBI pretreatment successfully mitigated ADA formation, the unexpected hepatic toxicity observed in this study warrants caution when considering OBI as an ADA mitigation strategy with other immune-stimulatory agents."

Clinical • IO biomarker • Metastases • P1 data • Melanoma • Oncology • Solid Tumor • Urothelial Cancer

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: Servier Bio-Innovation LLC | Trial completion date: Jul 2025 ➔ Apr 2026

Trial completion date • Oncology • Solid Tumor

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: Servier Bio-Innovation LLC | Trial completion date: Oct 2027 ➔ Jul 2025 | Trial primary completion date: Dec 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Immuno-positron Emission Tomography Study of 89Zr-S095012 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Jul 2023 ➔ Jun 2024 | Trial primary completion date: Jul 2023 ➔ Jun 2024

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Immuno-positron Emission Tomography Study of 89Zr-S095012 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Institut de Recherches Internationales Servier | N=33 ➔ 3 | Recruiting ➔ Terminated; Sponsor decision

Enrollment change • Metastases • Trial termination • Oncology • Solid Tumor

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: Servier Bio-Innovation LLC | N=130 ➔ 45

Enrollment change • Oncology • Solid Tumor

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Active, not recruiting | Sponsor: Servier Bio-Innovation LLC | Recruiting ➔ Active, not recruiting | Trial primary completion date: Oct 2027 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Oncology • Solid Tumor

Pieris loses Servier as partner for cancer immunotherapies (pharmaphorum) - "In a Securities & Exchange Commission (SEC) filing, Pieris said that Servier will exit the agreement between the two companies – first agreed in 2017 and focusing on the development of several Anticalin-based therapeutics for cancer – before the end of the year...The prompt for Servier's exit was a decision to stop dosing S095012 (formerly PRS-344), a 4-1BB/PD-L1 bispecific protein, in a phase 1 trial. Pieris said it intends to review the safety data from the S095012 study to understand the implications of the data, but does not intend to pursue any further development of the drug....Servier paid Pieris $31 million to start up the alliance, which spanned five bispecific drugs and could have been worth up to $1.8 billion. The lead drug at the time of signing was PRS-332, a CD223/PD-L1 bispecific protein that also seems to have fallen by the wayside."

Discontinued • Licensing / partnership • Trial termination • Oncology • Solid Tumor

Immuno-positron Emission Tomography Study of 89Zr-S095012 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Oct 2023 ➔ Sep 2025 | Trial primary completion date: Oct 2023 ➔ Jun 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Recruiting | Sponsor: Servier Bio-Innovation LLC | Trial completion date: Nov 2024 ➔ Oct 2027 | Trial primary completion date: Nov 2024 ➔ Oct 2027

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Assessment of target-mediated biodistribution of an 89Zr labeled PD-L1/4-1BB bispecific Mabcalin protein (AACR 2023) - "89Zr-Atezo-J10 specific accumulation in PD-L1 expressing tumors is due to both PD-L1 and 4-1BB binding and is higher than with PD-L1 and 4-1BB mono-targeting. This preclinical study supports the clinical evaluation of 89Zr-PRS-344/S095012’s whole-body distribution and the development of tumor-specific 4-1BB targeting bispecifics."

Cervical Cancer • Colon Cancer • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Oncology • TNFRSF9

Immuno-positron Emission Tomography Study of 89Zr-S095012 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: Institut de Recherches Internationales Servier | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Immuno-positron Emission Tomography Study of 89Zr-S095012 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Institut de Recherches Internationales Servier

New P1 trial • Oncology • Solid Tumor

Study of PRS-344/S095012 a PD-L1/4-1BB bispecific antibody-Anticalin®-fusion in patients with solid tumors (AACR 2022) - P1/2 | "Phase 2 is an expansion with primary objective of anti-tumor activity. First patient was dosed in November 2021 and the study is planned to enroll at sites in Belgium, Spain and Australia."

Clinical • IO biomarker • Oncology • Solid Tumor

Pieris Pharmaceuticals Reports Second Quarter 2022 Financial Results and Provides Corporate Update (Issuer Direct) - "PRS-344/S095012 and Servier Collaboration: Pieris and Servier continue to enroll the escalation portion of the phase 1/2 study of PRS-344/S095012, a 4-1BB/PD-L1 Anticalin-based bispecific for the treatment of solid tumors for which Pieris holds full U.S. rights and will receive royalties on ex-U.S. sales by Servier. The companies expect to initiate expansion cohorts in jointly-vetted indications next year....PRS-342/BOS-342: Boston Pharmaceuticals continues to advance PRS-342/BOS-342, a 4-1BB/GPC3 bispecific, towards the clinic, with phase 1 expected to begin in the first half of 2023."

New P1 trial • Trial status • Oncology • Solid Tumor

Anticalin®-based therapeutics: Expanding new frontiers in drug development. (PubMed, Int Rev Cell Mol Biol) - "The small size and stable structure support their development as inhalable biologics in the field of respiratory diseases as already demonstrated for PRS-060/AZD1402, an Anticalin protein currently undergoing clinical development for the treatment of asthma. Cinrebafusp alfa and PRS-344/S095012 antibody-Anticalin bispecific proteins were designed to reduce potential systemic toxicity by localizing the activity to the tumor, and are currently in clinical development in immuno-oncology. Furthermore, the ease in generating bi- and multispecifics as well as the small and stable structure prompted the investigation of Anticalin proteins for the CAR T space, opening additional potential treatment options based on Anticalin protein therapies."

Journal • Asthma • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Recruiting | Sponsor: Pieris Pharmaceuticals, Inc. | N=45 ➔ 130

Enrollment change • Oncology • Solid Tumor

The PD-L1/4-1BB bispecific antibody-Anticalin fusion protein PRS-344/S095012 elicits strong T-cell stimulation in a tumor-localized manner (CIMT 2022) - "We finally provide evidence that soluble 4-1BB is a potential biomarker of 4-1BB agonism in patients. Taken together our preclinical data outline proof of concept for the functionality of PRS-344/S095012 and support further clinical development of this drug candidate."

IO biomarker • Immune Modulation • Inflammation • Oncology • TNFRSF9

The PD-L1/4-1BB bispecific Antibody-Anticalin fusion protein PRS-344/S095012 elicits strong T-cell stimulation in a tumor-localized manner. (PubMed, Clin Cancer Res) - "The PD-L1/4-1BB bispecific PRS-344/S095012 efficiently combines checkpoint blockade with a tumor-localized 4-1BB mediated stimulation burst to antigen-specific T cells, more potent than the combination of mAbs, supporting the advancement of PRS-344/S095012 towards clinical development."

IO biomarker • Journal • Immune Modulation • Inflammation • Oncology • Transplantation • CD4 • CD8

The PD-L1/4-1BB bispecific Antibody-Anticalin fusion protein PRS-344/S095012 elicits strong T-cell stimulation in a tumor-localized manner. (PubMed, Clin Cancer Res) - "The PD-L1/4-1BB bispecific PRS-344/S095012 efficiently combines checkpoint blockade with a tumor-localized 4-1BB mediated stimulation burst to antigen-specific T cells, more potent than the combination of mAbs, supporting the advancement of PRS-344/S095012 towards clinical development."

IO biomarker • Journal • Immune Modulation • Inflammation • Oncology • Transplantation • CD4 • CD8

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors (clinicaltrials.gov) - P1/2; N=45; Recruiting; Sponsor: Pieris Pharmaceuticals, Inc.

Clinical • New P1/2 trial • Oncology • Solid Tumor

Pieris Pharmaceuticals and Servier Announce Dosing of First Patient in Phase 1/2 Trial of 4-1BB/PD-L1 Bispecific PRS-344/S095012 (PipelineReview) - "Pieris Pharmaceuticals, Inc...announced that the first patient has been dosed in the phase 1/2 study of PRS-344/S095012, a next generation 4-1BB/PD-L1 Anticalin-based bispecific for the treatment of solid tumors, triggering an undisclosed milestone payment to Pieris."

Trial status • Oncology • Solid Tumor

Pieris Pharmaceuticals Reports Second Quarter 2021 Financial Results and Provides Corporate Update (Issuer Direct) - “Cinrebafusp Alfa (PRS-343): Pieris plans to dose the first patient in a two-arm phase 2 study for cinrebafusp alfa, a 4-1BB/HER2 bispecific for the treatment of HER2-expressing solid tumors, in gastric cancer in the coming weeks…The Company expects to report results from both study arms next year…PRS-344/S095012 and Servier Collaboration: The phase 1 study of PRS-344/S095012, a 4-1BB/PD-L1 bispecific, is expected to begin later this year.”

New P1 trial • New P2 trial • P2 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor