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OS Therapies is moving ahead with plans for an accelerated approval pathway after its off-the-shelf candidate for people who have had surgery to treat osteosarcoma succeeded in a single-arm mid-stage study. The New York-based biotech’s HER2-targeted immunotherapy, dubbed OST-HER2, achieved statistical significance in the Phase 2b primary endpoint of event-free survival (EFS) at 12 months, according to a Wednesday release. The drugmaker’s shares $OSTX were up by around 48% at the start of trading on Wednesday. Around one-third of 39 evaluable subjects aged 12 to 39 with recently resected osteosarcoma with metastases that had recurred in the lungs were free of disease recurrence following treatment with OST-HER2. This compares well with the 20% EFS seen with historical control, according to the drugmaker. In the trial’s secondary survival endpoint, interim results showed 91% of patients given OST-HER2 were still alive at one year compared with 80% for historical control, good for a p-value of 0.07. The data come after OS Therapies announced in October that the final patient in the trial had completed their last visit. A month later, the company secured $6 million in a private placement. The biotech is now planning to engage with the FDA on a potential accelerated approval path for the treatment candidate, CEO Paul Romness said in the release. Romness has previously held roles at Johnson & Johnson, Amgen and Boehringer Ingelheim. There are currently no FDA-approved treatments to prevent recurrent, fully resected, lung metastatic osteosarcoma. The disease often starts in the bones of the legs or arms and affects just 1,000 people in the US each year, but is the most common malignant bone tumor in children and young adults. Around half of all patients are diagnosed with lung metastasis at some point after surgery and chemotherapy, according to OS Therapies. Other drugmakers developing treatments for osteosarcoma include Umoja Biopharma, which is advancing an in vivo CAR-T therapy called UB-TT170 for the disease. Denmark-based ADC biotech Adcendo is homing in on targeting uPARAP , a collagen receptor that’s overexpressed in cancers, including osteosarcoma. Elsewhere, OS Therapies’ OST-HER2 is also being developed for breast cancer and other solid tumors, although a Phase 2a trial in those indications is currently on hold as the company waits for an osteosarcoma approval. The asset is designed to stimulate the body’s immune system to fight cancer better by training HER2-specific T cells to detect and destroy cancer cells. Editor’s note: This article was updated to add the company’s stock movement.

Danish biotech Adcendo is joining the antibody-drug conjugate megaround train. Adcendo has corralled a $135 million Series B led by TCGX. And according to an Endpoints News tally, of the 88 biotech startups to raise a nine-figure financing round in 2024, 11 are working on ADCs. The Copenhagen-based biotech, which has partnerships with Multitude Therapeutics and Duality Biologics , is working on new types of ADCs and will enter the clinic “soon” with its first asset and again in early 2025 with its second experimental medicine in the hot class, CEO Michael Pehl told Endpoints News in an email. Adcendo could consider the public markets once it has early clinical data from those first two ADCs — a Topo1-based tissue factor-targeting ADC licensed from Multitude called ADCE-T02 and a uPARAP targeting pan-sarcoma ADC named ADCE-D01 . “We think that a US IPO, backed by a strong clinical data package from ADCE-T02 and ADCE-D01, is a very attractive option for Adcendo,” the CEO added. Prior to Adcendo, Pehl ran ADC biotech Immunomedics for a brief stretch from late 2017 until the spring of 2019 . Gilead bought Immunomedics in a deal worth $21 billion about 18 months later. The Series B will bring those two ADCs to clinical proof of concept, fund a dose-escalation study of another asset codenamed ADCE-B05 and take a fourth, dubbed A0401, to an IND filing, Pehl said. Adcendo is exploring work in the area of uPARAP, a collagen receptor that is overexpressed in cancers like soft-tissue sarcoma, osteosarcoma, mesothelioma and glioblastoma multiforme. The recycling endocytic receptor is viewed as a “highly efficient entry for ADCs” that target cells expressing the receptor, the company said. The 40-employee biotech was formed in 2017 as a spinout from the Finsen Laboratory of Rigshospitalet and the University of Copenhagen. It unveiled a $62 million Series A in April 2021 and topped that round off multiple times over the years, including another €16 million in May. In addition to TCGX, its new investors also include TPG Life Sciences Innovations , OrbiMed, Venrock Healthcare Capital Partners , Surveyor Capital and Logos Capital. All existing investors also took part in the Series B, including RA Capital Management, Novo Holdings and others.

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Incendia Therapeutics, formerly Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today announced that it will have two poster presentations at the European Society for Medical Oncology (ESMO) Congress 2023, to be held in Madrid, Spain October 20-24, 2023. The company will present data on the expression of discoidin domain receptor 1 (DDR1) mRNA and protein across 20 tumor types and will provide a detailed overview of Incendia’s Phase 1 first-in-human clinical trial for its lead candidate PRTH-101 in patients with advanced solid tumors (NCT05753722). “The tumor microenvironment is dramatically impacted by the over expression of DDR1 and its role in the alignment of collagen fibers, which ultimately prevents immune cells from being able to directly interact with tumors,” said Laura Dillon, Vice President of Translational Medicine and Bioinformatics at Incendia. “These data presented at ESMO further highlight the potential of PRTH-101 as a first-in-class DDR1 inhibitor that may address the unmet need in the numerous cancers with high DDR1 expression.” Presentation Details: Title: High DDR1 mRNA and Protein Expression Across Human Tumor Types Correlate with Epithelial Composition of the Tumor Microenvironment Lead author: Laura Dillon, Ph.D., Vice President, Translational Medicine and Bioinformatics at Incendia Therapeutics Presentation #: 2309P Presentation Time: Saturday, October 21, 12:00 - 1:00 PM CEST (6-7 AM ET) Translational Research (agnostic) Key Highlights: DDR1 is expressed in a high proportion of tumor cells across a range of epithelial tumor types, suggesting potentially broad application of DDR1-targeted therapies. A high proportion of tumor cells (median of 0.76) expressed DDR1 across all epithelial tumor types. DDR1 expression was uniformly low in mesenchymal tumors (median of 9 cells/mm2) compared to epithelial tumors (median of 2803 cells/mm2). Moderate correlation was observed between DDR1 mRNA expression and DDR1+ cell density across tumor types (R=0.48, p<0.0001). In epithelial tumors, both DDR1 mRNA and protein expression were correlated with the percentage of epithelium (R=0.37 and 0.56, respectively; both p<0.0001), with significant variance between tumor types. Title: A Phase 1 First-in-Human Study of PRTH-101, an IgG1 Monoclonal Antibody Targeting DDR1, as a Monotherapy and Combined with Pembrolizumab in Patients with Advanced Solid Malignancies Lead author: Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of NEXT Oncology Dallas Presentation #: 1079TiP Presentation Time: Monday, October 23, 12:00 – 1:00 PM CEST (6-7 AM ET) (Investigational immunotherapy) Key Highlights: Discoidin domain receptor 1 (DDR1) is a collagen receptor that represents a promising therapeutic target due to its role in excluding lymphocytes from the tumor microenvironment (TME) by aligning collagen fibers. DDR1 expression is high in multiple cancer types and associated with worse survival. PRTH-101 is a humanized IgG1 antibody that binds to the extracellular domain of both membrane-bound and soluble DDR1. In preclinical models, PRTH-101 monotherapy resulted in disruption of aligned collagen fibers in the tumor stroma, increased infiltration of lymphocytes, and tumor growth inhibition. When PRTH-101 is combined with PD-1 inhibition, activated T cell infiltration is increased compared to PRTH-101 alone. This is a Phase 1 first-in-human study that will evaluate intravenous PRTH-101 +/- pembrolizumab in patients with advanced solid tumors. Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints will be monitored and reported. The first part of the study (Ph1a) seeks to identify the maximum tolerated dose (MTD) or optimal biologic dose (OBD), of PRTH-101 to determine the recommended phase 2 dose (RP2D). The second part (Ph1b) seeks to identify the MTD or OBD of PRTH-101 in combination with pembrolizumab to determine the PRTH-101 combination RP2D. The third part (Ph1c) consists of dose expansion in disease-directed cohorts to assess the anti-tumor efficacy of PRTH-101 monotherapy and/or combination therapy. About PRTH-101 PRTH-101 is a therapeutic antibody that specifically binds to and blocks discoidin domain receptor 1 (DDR1,) a protein expressed on tumor cells that binds collagen to make a physical barrier that prevents immune cells from interacting with and attacking tumor cells. By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and attack the tumor. Blockade of DDR1 represents a unique approach to stimulating immune-based antitumor activity, and in preclinical models such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade. Tumor types that express high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1. About Incendia Therapeutics Incendia Therapeutics is discovering and developing a novel class of anti-cancer therapies that reprogram the tumor microenvironment (TME). Recent research has shown that the interplay between tumor cells and their surrounding TME results in the creation of barriers that markedly attenuate the immune system’s ability to attack the tumor. Based on rigorous, groundbreaking research, Incendia is developing a portfolio of drug candidates to treat select patients at the appropriate/ideal stage in disease progression. For more information visit incendia.com and LinkedIn.