On October 8, 2024 Blue Earth Therapeutics Ltd, an emerging leader in the development of therapeutic radiopharmaceuticals, reported further positive developments for its novel investigational radioligand therapies (Press release, Blue Earth Therapeutics, OCT 8, 2024, View Source [SID1234647093]). Enrolment of patients in the Phase 1 trial of Lutetium (177Lu) rhPSMA-10.1 Injection was completed in July. Early data from the trial suggests an encouraging safety profile. Radiation dosimetry performed for up to three cycles showed delivery of high tumour absorbed radiation doses relative to the dose delivered to the key normal organs, such as kidney and salivary glands. While final analysis is ongoing, the ratio between radiation dose to tumours vs. dose to the kidneys and salivary glands was compelling vs. published data1 for first generation radioligand therapies.

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This data opens the way for the Phase 2 portion of the Phase 1/2 trial to start later this year. The company has shared the intended Phase 2 study design with regulators and, subject to trial safety committee agreement, will test innovative dosing regimens in the Phase 2 study. Based on the advantageous results for absolute tumour and normal organ uptake seen in Phase 1, the Phase 2 study will explore the following concepts:

Administration of a significantly higher overall injected radioactivity in comparison to recent Phase 3 clinical trials of other agents.
Front loading of administered radioactivity.
Extending duration of administration of radioactivity to provide longer time on treatment.
In combination with the positive radiation dosimetry results seen in Phase 1 for Lutetium (177Lu) rhPSMA-10.1 Injection, these factors should further support the ultimate goal of delivering better outcomes for patients.

"We are excited by the new data which support our best-in-class thesis and to have a clear path to move from Phase 1 to Phase 2 in the development of our lead therapy," said David Gauden, CEO. "We remain on track for the opening of Phase 2 in the next few months. We also expect to see the full Phase 1 results presented at a scientific meeting in 2025."

"The available science increasingly highlights that fixed dosing at fixed intervals is unlikely to be optimal. Front loading radioactivity and extending the time on therapy may lengthen time to disease progression. We will explore these concepts in Phase 2. Our intention is to optimize dosing now, with the aim of achieving the best possible outcomes for patients in a future pivotal trial," commented Dr Daniel Stevens, Head of Clinical Development and Medical at Blue Earth Therapeutics. "We think that adapting dosing based on data from the individual patient will be important for improved results."

The Phase 2 clinical trial of Lutetium (177Lu) rhPSMA-10.1 Injection is planned to open at approximately 15 sites across the US and Europe and enroll approximately 70 patients.

1 Ells, Zachary, et al. "Dosimetry of [177Lu] Lu-PSMA-Targeted Radiopharmaceutical Therapies in Patients with Prostate Cancer: A Comprehensive Systematic Review and Meta analysis." Journal of Nuclear Medicine (2024).

About Radiohybrid Prostate‐Specific Membrane Antigen (rhPSMA)
rhPSMA compounds are referred to as radiohybrid ("rh"), as each molecule possesses four distinct domains. The first consists of a Prostate‐Specific Membrane Antigen‐targeted receptor ligand. It is attached to two labelling moieties which may be radiolabeled with diagnostic isotopes such as 18F or 68Ga for PET imaging, or with therapeutic isotopes such as 177Lu or 225Ac for radioligand therapy, all of which are joined together by a modifiable linker which can be used to modulate important pharmacokinetic characteristics. Radiohybrid PSMA offers the potential for targeted treatment for men with prostate cancer and originated at the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics.

On October 8, 2024 Kintara Therapeutics reported its Fiscal 2024 Financial Results and Provides Corporate Update (Press release, Kintara Therapeutics, OCT 8, 2024, View Source [SID1234647166]).

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On October 8, 2024 Adcendo, a biotech company focused on the development of first-in-class ADCs for the treatment of cancers with a high unmet medical need, reported that the US Food & Drug Administration (FDA) has provided clearance of the IND application for the Phase I/II study of ADCE-D01 in patients with metastatic and/or unresectable STS (the ADCElerate-01 Trial) (Press release, ADCendo, OCT 8, 2024, View Source [SID1234647094]).

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ADCElerate-01 is a first-in-human Phase I/II multicenter, open-label, dose escalation and expansion study of ADCE-D01 as a monotherapy in patients with metastatic and/or unresectable STS. The primary objective of the study is to evaluate the safety and tolerability of ADCE-D01, to determine the maximum tolerated dose, as well as the recommended Phase II dose and schedule of ADCE-D01 monotherapy. The secondary objectives are to characterize the pharmacokinetics and to evaluate the preliminary efficacy of ADCE-D01. The study will recruit in the US and Europe, with a CTIS submission planned in the EU during the coming months.

Dr. Lone Ottesen, Chief Medical Officer of Adcendo, said: "uPARAP is a highly attractive target for the development of an ADC in mesenchymal cancers including soft tissue sarcoma, as it is highly overexpressed in multiple STS subtypes, has unique internalization properties and shows only very low expression in healthy tissues. The IND clearance of ADCE-D01 is an important milestone for our program and our company, and we look forward to initiating patient enrolment for this study and working with our investigators to evaluate the therapeutic utility of this drug in STS patients as soon as possible."

Prof. Patrick Schöffski, Head of the Department of General Medical Oncology at the University Hospitals and the Laboratory of Experimental Oncology at the Catholic University in Leuven (KU Leuven), and Principal investigator of the ADCElerate-01 trial, commented: "Patients with metastatic soft tissue sarcoma have very limited treatment options and an extremely poor prognosis. We are intrigued by the biology and expression profile of uPARAP, as well as the extensive pre-clinical data package generated for ADCE-D01. ADCs have already significantly altered the therapeutic landscape for many solid tumor indications, and we are excited to be working with Adcendo to develop a potential pan-sarcoma ADC for our STS patients."

About ADCE-D01:

ADCE-D01 is an antibody-drug conjugate targeting the uPARAP receptor. uPARAP is a recycling endocytic receptor involved in collagen homeostasis and turnover. uPARAP exhibits a limited expression profile in healthy tissues but is highly upregulated in multiple mesenchymal cancers, including soft tissue sarcoma, bone sarcoma, GIST as well as mesothelioma and glioblastoma, making it a highly attractive target for ADC development.

On October 8, 2024 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported multiple presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 39th Annual Meeting, being held November 6-10, 2024, in Houston, TX (Press release, Sapience Therapeutics, OCT 8, 2024, View Source [SID1234647095]).

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Presentation details are below:

ST101 Presentation Details (Oral Presentation and Poster):

Title: "ST101, an inhibitor of the transcription factor C/EBPß, promotes an immune-active tumor microenvironment in a window of opportunity (WoO) study of patients with glioblastoma (GBM)"
Abstract #: 991

Oral Presentation
Session Title: Biotech Breakthroughs – Solid Tumor IO at the Tipping Point
Date/Time: Friday, November 8, 2024, 1:45 pm – 3:20 pm CST
Session Location: George R. Brown Convention Center, Level 3 – Grand Ballroom B
Presenting Author: Jim Rotolo, Ph.D., SVP, Research & Translational Sciences, Sapience Therapeutics

Poster Presentation
Session: Poster Hall
Date/Time:

Friday, November 8, 2024: 9:00 am – 7:00 pm CST
Saturday, November 9, 2024: 9:00 am – 8:30 pm CST
Session Location: George R. Brown Convention Center, Level 1 – Exhibit Halls AB

ST316 Poster Presentation Details:

Title: "ST316, a peptide antagonist of ß-Catenin, depletes immunosuppressive myeloid cell populations and enhances anti-cancer immune responses in in vivo tumor models and in patients"
Abstract #: 1451
Session: Poster Hall

Date/Time:

Friday, November 8, 2024, 9:00 am – 7:00 pm CST
Saturday, November 9, 2024, 9:00 am – 8:30 pm CST
Session Location: George R. Brown Convention Center, Level 1 – Exhibit Halls AB
Presenting Author: Claudio Scuoppo, Ph.D., Principal Scientist, Sapience Therapeutics

More information can be found on the SITC (Free SITC Whitepaper) website.

About ST101
ST101, a first-in-class antagonist of C/EBPβ, has completed the main portion of a Phase 2 dose expansion study in recurrent GBM (rGBM) (NCT04478279). An ongoing window-of-opportunity sub-study is evaluating ST101 as a monotherapy in patients with rGBM and in combination with radiation and temozolomide in patients with newly diagnosed GBM (ndGBM), with patients receiving ST101 before and after surgical resection in both cohorts. ST101 has been granted Fast Track designation for rGBM from the U.S. FDA and orphan designations for glioma from the U.S. FDA and the European Commission.

About ST316
ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex responsible for driving oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. ST316 is being evaluated in the Phase 2 portion of a Phase 1-2 dose-escalation and expansion study (NCT05848739). The Phase 1 portion completed enrollment in July 2024. In the Phase 2 dose expansion, ST316 is being tested in colorectal cancer patients in combination with relevant standards of care and in multiple lines of treatment. Sapience is conducting the Phase 2 study across several sites in the United States.

On October 7, 2024 BPGbio, Inc., a leading biology-first, AI-powered, clinical stage biopharma focused on mitochondrial biology and protein homeostasis, and the University of Oxford’s Centre for Medicines Discovery, reported a five-year research collaboration focused on advancing novel protein degradation technologies, particularly in oncology and central nervous system (CNS) diseases, with the goal of unlocking new therapeutic pathways for conditions with limited treatment options (Press release, BPGbio, OCT 7, 2024, View Source [SID1234647077]). The organizations will work in phases, starting with the validation of BPGbio’s novel E2 TPD technology, and expanding into future study of the degradable target space, to identify novel targets and generate high quality publications.

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This collaboration builds on BPGbio’s first-in-class E2-based protein degradation program, which features a proprietary library of more than 1,000 Ro3 fragments discovered by BPGbio that are potential ligands and seed compounds to a variety of E2 targets. The collaboration will also utilize BPGbio’s proprietary ternary structures, its computational toolkit for E2 ligand design, and assays for rapidly attaining selectivity and specificity.

The partnership will leverage the Centre for Medicines Discovery’s expertise in translational research, including their groundbreaking efforts in neurological diseases such as Parkinson’s Disease. The team will utilize BPGbio’s proprietary NAi Interrogative Biology Platform, which integrates patient biology with AI-driven analysis, to accelerate biomarker discovery and therapeutics development.

"This collaboration represents a powerful alliance of biology-first science and cutting-edge translational research," said Niven R. Narain, Ph.D., President and CEO of BPGbio. "By harnessing our NAi Interrogative Biology Platform alongside the University of Oxford’s expertise, we aim to push the boundaries of protein degradation science and deliver transformative therapies for diseases like cancer and CNS disorders, where unmet medical needs remain significant."

"By partnering with BPGbio, we’re combining our world-class translational research expertise with their pioneering approach to protein degradation," said Prof. Paul Brennan, Ph.D., FRSC, Director of the Centre for Medicines Discovery at University of Oxford. "This collaboration has the potential to unlock new therapeutic strategies for diseases that have long resisted treatment, including challenging cancers and CNS disorders. We are excited to explore novel targets and bring forward breakthrough therapies that could make a profound difference for patients."