An Open-Label Phase 1 Dose-Escalation and Expansion Study Investigating the Safety, Pharmacokinetics, Pharmacodynamics, and Activity of PRTH-101 Alone or in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors

The goal of this Open-Label Study is to evaluate the safety and tolerability of PRTH-101 alone or in combination with pembrolizumab in adults with advance or metastatic solid tumors.

Start Date03 Mar 2023

Sponsor / Collaborator

Incendia Therapeutics, Inc.Startup

100 Clinical Results associated with PRTH-101

100 Translational Medicine associated with PRTH-101

100 Patents (Medical) associated with PRTH-101

Literatures (Medical) associated with PRTH-101

01 Jun 2023·Journal for immunotherapy of cancer

A highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer

Article

Author: Laurent, Victor ; Liu, Junquan ; Zhang, Ningyan ; Audoly, Laurent P ; An, Zhiqiang ; Xiong, Wei ; Li, Wenliang ; Schürpf, Thomas ; Griffiths, Samuel C ; Dülfer, Jasmin ; Deng, Hui ; Li, Rong ; Chiang, Huai-Chin ; Yin, Y Whitney ; Sun, Xiujie

Background:

Immune exclusion (IE) where tumors deter the infiltration of immune cells into the tumor microenvironment has emerged as a key mechanism underlying immunotherapy resistance. We recently reported a novel role of discoidin domain-containing receptor 1 (DDR1) in promoting IE in breast cancer and validated its critical role in IE using neutralizing rabbit monoclonal antibodies (mAbs) in multiple mouse tumor models.

Methods:

To develop a DDR1-targeting mAb as a potential cancer therapeutic, we humanized mAb9 with a complementarity-determining region grafting strategy. The humanized antibody named PRTH-101 is currently being tested in a Phase 1 clinical trial. We determined the binding epitope of PRTH-101 from the crystal structure of the complex between DDR1 extracellular domain (ECD) and the PRTH-101 Fab fragment with 3.15 Å resolution. We revealed the underlying mechanisms of action of PRTH-101 using both cell culture assays andin vivostudy in a mouse tumor model.

Results:

PRTH-101 has subnanomolar affinity to DDR1 and potent antitumor efficacy similar to the parental rabbit mAb after humanization. Structural information illustrated that PRTH-101 interacts with the discoidin (DS)-like domain, but not the collagen-binding DS domain of DDR1. Mechanistically, we showed that PRTH-101 inhibited DDR1 phosphorylation, decreased collagen-mediated cell attachment, and significantly blocked DDR1 shedding from the cell surface. Treatment of tumor-bearing mice with PRTH-101in vivodisrupted collagen fiber alignment (a physical barrier) in the tumor extracellular matrix (ECM) and enhanced CD8+T cell infiltration in tumors.

Conclusions:

This study not only paves a pathway for the development of PRTH-101 as a cancer therapeutic, but also sheds light on a new therapeutic strategy to modulate collagen alignment in the tumor ECM for enhancing antitumor immunity.

News (Medical) associated with PRTH-101

28 Oct 2024

·www.prnewswire.com

DELFI Diagnostics Working with Incendia Therapeutics to Employ Advanced Treatment Monitoring Test in a Phase 1 Clinical Trial

Innovative Assay Aims to Enhance Patient Outcomes through Precision Medicine PALO ALTO, Calif. and CAMBRIDGE, Mass., Oct. 28, 2024 /PRNewswire/ -- DELFI Diagnostics, Inc., a developer of accessible blood-based tests that deliver a new way to enhance cancer detection, today announced that Incendia Therapeutics will use the DELFI-TF Monitoring assay as part of their suite of assays for evaluation of treatment response and disease progression in patients enrolled in their Phase I clinical trial (NCT05753722). Continue Reading Incendia Therapeutics is discovering and developing a novel class of experimental therapeutics that reprogram the tumor microenvironment (TME). "Incendia is committed to the development of novel, precision medicines for patients in need. Innovative products, such as those being developed by DELFI, will aid in the efficient progress of those medicines through the clinic," said Susan Macdonald, PhD, SVP Nonclinical Development & Strategy at Incendia Therapeutics, commenting on how the relationship leverages the strengths of both companies to bring a state-of-the-art detection tool to scientific researchers looking to develop precise treatment monitoring. "The DELFI-TF assay provides a unique, cost-effective approach to monitoring cfDNA from patients in clinical research studies, providing evidence of the efficacy of a New Molecular Entity (NME) in the earliest phases of clinical development," said DELFI Diagnostics Co-Founder and Chief Scientific Officer, Nicholas Dracopoli. "The DELFI-TF assay will provide Incendia with valuable insights to help them manage their Phase 1 program." One key advantage of the DELFI TF assay is that it requires under 1 mL of plasma — considerably less than the volume needed for other cfDNA assays. This low volume is particularly beneficial in early clinical studies that require large volumes of blood for other assessments, such as pharmacokinetic (PK) analyses. About DELFI Diagnostics DELFI Diagnostics is developing next-generation, blood-based tests that are accurate, accessible, and deliver a new way to help detect cancer. DELFI tests are built to solve the highest-burden population health issues, including in historically underserved demographics, and have the potential to save lives on a global scale. FirstLook Lung, for individuals eligible for lung cancer screening, is our first laboratory-developed screening test and requires a simple blood draw that can be incorporated with routine blood work. The test is based on fragmentomics, the discovery that cancer cells are more chaotic than normal cells and, when they die, leave behind tell-tale patterns and characteristics of cell-free DNA (cfDNA) fragments in the blood. The DELFI platform applies advanced machine-learning technology to whole-genome sequencing data to assess individuals' cfDNA fragments against populations with and without cancer. FirstLook Lung uses these millions of data points to reliably identify individuals who may have cancer detected through low-dose CT, including early-stage disease, with a negative predictive value of 99.8 percent. This test has not been cleared or approved by the FDA. To learn more about the FirstLook Lung test, visit or . About Incendia Therapeutics Incendia Therapeutics is discovering and developing a novel class of experimental therapeutics that reprogram the tumor microenvironment (TME). Incendia's platform is based on rigorous, groundbreaking research involving spatial characterization of the tumor microenvironment, multi-omics data integration, and extensive preclinical testing. The Company's most advanced experimental molecule, PRTH-101, is in a Phase 1 clinical trial for the treatment of patients with advanced solid tumors. For more information visit incendiatx.com and LinkedIn. SOURCE DELFI Diagnostics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1

10 Sep 2024

·pipelinereview.com

Incendia Therapeutics Enrolls First Patient in Phase 1c Clinical Trial of PRTH-101, a Novel DDR1 Inhibitor

Phase 1c study of PRTH-101 alone or in combination with KEYTRUDA® in patients with advanced or metastatic solid tumors will inform optimal design of the Phase 2/3 study PRTH-101 demonstrated favorable safety profile in Phase 1a and 1b studies CAMBRIDGE, MA, USA I September 10, 2024 I Incendia Therapeutics , a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today announced that the first patient has been enrolled in the Phase 1c study of PRTH-101 for the treatment of patients with advanced or metastatic solid tumors. “In our Phase 1a and 1b studies, we were able to select an optimal dose and identify potential biomarkers to carry forward” said Irena Webster, SVP Development and Operations of Incendia. “The data from this study will inform the design of the Phase 2/3 program, for which planning and global feasibility are currently underway.” Dr. Joseph Paul Eder, CMO, added “Incendia, with its outstanding team of investigators and investigative sites, has determined a recommended Phase 2 dose of PRTH 101. PRTH 101 has shown consistent safety as a single agent and in combination with pembrolizumab. We will now focus on tumor types that have demonstrated signs of clinical activity and patient benefits.” The Phase 1c study will evaluate the safety, tolerability and anti-tumor activity of PRTH-101 as both a monotherapy and in combination with KEYTRUDA® (pembrolizumab). About PRTH-101 PRTH-101 is a therapeutic antibody that targets DDR1, a collagen binding protein and kinase present on epithelial cells. Some tumor cells are believed to co-opt DDR1 – collagen binding to build an impenetrable barrier around the tumor. By allosterically disabling DDR1, PRTH-101 disrupts tumor associated collagen alignment to permit immune cell access into the tumor core. In preclinical experiments, PRTH-101 mediated DDR1 blockade has demonstrated both single agent anti-tumor activity as well as marked augmentation of checkpoint inhibitor function. Tumor types that express high levels of DDR1-associated collagen barriers include thymic, colorectal, pancreatic, ovarian, glioma, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1. About the Phase 1 Trial The Phase 1 trial ( NCT05753722 ) is a multi-center, open-label, dose escalation and dose expansion study that is expected to enroll up to 270 patients in the US with advanced or metastatic solid tumors. The goals of the study are to assess safety and tolerability of PRTH-101, evaluate anti-tumor activity in select indications alone and in combination with anti-PD-1 inhibitors, and determine dosing regimens for the Phase 2 clinical program. In addition to examining the clinical profile of PRTH-101, the trial will evaluate DDR1 and pathway-related proteins as predictive biomarkers for patients whose tumors respond to treatment. About Incendia Therapeutics Incendia Therapeutics is discovering and developing a novel class of experimental therapeutics that reprogram the tumor microenvironment (TME). Incendia’s platform is based on rigorous, groundbreaking research involving spatial characterization of the tumor microenvironment, multi-omics data integration, and extensive preclinical testing. The Company’s most advanced experimental molecule, PRTH-101, is in a Phase 1c clinical trial for the treatment of patients with advanced solid tumors. For more information visit incendia.com and LinkedIn . SOURCE: Incendia Therapeutics

Phase 1Clinical Result

23 May 2024

·www.biospace.com

Incendia Therapeutics Announces Upcoming Presentation with PathAI at the 2024 American Society of Clinical Oncology Annual Meeting

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Incendia Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today announced that it will present data in collaboration with PathAI, a leading AI-powered precision pathology company at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31 – June 4, 2024 in Chicago, Illinois. “I am delighted to be sharing more from our exciting collaboration with PathAI in a poster session at ASCO, highlighting the potential of utilizing digital pathology-based biomarkers to predict outcome in a clinical setting,” said Laura Dillon, PhD, Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics. “The data demonstrate the correlation between immune phenotypes predicted from hematoxylin and eosin (H&E)-stained whole slide images and survival following checkpoint inhibitor therapy in non-small cell lung cancer (NSCLC). We believe these data support the possibility of improving patient outcomes in NSCLC by advancing the identification of PD-L1(-) patients who may derive greater benefit from treatment with check-point inhibitors.” Presentation details for ASCO 2024 are as follows: Title: Correlation of immune phenotypes derived from H&E-stained whole slide images with prognosis and response to checkpoint inhibitors in NSCLC Abstract Number: 8539 Presenting Authors: Bahar Rahsepar, Senior AI Product Manager at PathAI, Inc. and Laura Dillon, Ph.D., Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics Poster Session: Lung Cancer—Non-Small Cell Metastatic Date and Time: Monday, June 3 from 1:30 - 4:30 PM CDT (2:30 – 5:30 PM EDT) Key Highlights: The classification of tumors as inflamed, excluded or desert based on spatial patterns of tumor infiltrating lymphocytes (TILs) is a potential biomarker of patients likely to respond to checkpoint inhibitors (CPI). However, the subjectivity of manual methods to assess these immune phenotypes (IPs) and poor standardization in the methods and thresholds to define IPs have hampered their clinical adoption. Using a data-driven approach for predicting IPs using patch-level TIL features, AI model-predicted IPs were prognostic in The Cancer Genome Atlas (TCGA) NSCLC dataset and predictive of progression free survival (PFS) in a CPI- treated clinical NSCLC cohort. Association of IP and PFS was independent of PD-L1 status, potentially allowing the identification of PD-L1(-) patients who may derive greater benefit from CPI. In The Cancer Genome Atlas (TCGA) NSCLC cohort, model-predicted inflamed immune phenotypes (IP) (iIP) (N=196) and excluded IP (eIP) (N=607) patients had significantly better overall survival (OS) compared to desert IP (dIP) (N=80; HR=0.53, p=0.003 and HR=0.59, p=0.003, respectively). In the clinical cohort, cancer tumor infiltrating lymphocytes density and fraction of hot epithelial patches were significantly associated with (PFS) (HR=0.64, q=0.04 and HR=0.69, q=0.04, respectively). PFS was significantly shorter in model-predicted eIP patients (N=46) compared to iIP (N=39; HR=0.54, p=0.045). Notably, in PD-L1(-) patients (N=43, tumor proportion score ≤1%), iIP patients had longer PFS than eIP and dIP patients (HR=0.35, p=0.02). No difference in PFS was observed for PD-L1(+) patients. About Incendia Therapeutics Incendia Therapeutics is discovering and developing a novel class of experimental therapeutics that reprogram the tumor microenvironment (TME). Incendia’s platform is based on rigorous, groundbreaking research involving spatial characterization of the tumor microenvironment, multi-omics data integration, and extensive preclinical testing. The Company’s most advanced experimental molecule, PRTH-101, is in a Phase 1 clinical trial for the treatment of patients with advanced solid tumors. For more information visit incendia.com and LinkedIn.

ASCOPhase 1ImmunotherapyClinical ResultCell Therapy

100 Deals associated with PRTH-101

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	US	Incendia Therapeutics, Inc.Startup	03 Mar 2023
Metastatic Solid Tumor	Phase 1	US	Incendia Therapeutics, Inc.Startup	03 Mar 2023

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