Trauma therapies for psychosis: A state-of-the-art review.

Background: Traumatic events, particularly childhood interpersonal victimisation, have been found to play a causal role in the occurrence of psychosis and shape the phenomenology of psychotic experiences. Higher rates of post-traumatic stress disorder (PTSD) and other trauma-related mental health problems are also found in people with psychosis diagnoses compared to the general population. It is, therefore, imperative that therapists are willing and able to address trauma and its consequences when supporting recovery from distressing psychosis.

BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for Treatment of Solid Tumors.

Multiple tumor types overexpress Nectin-4 and the antibody-drug conjugate (ADC), enfortumab vedotin (EV) shows striking efficacy in clinical trials for metastatic urothelial cancer, which expresses high levels of Nectin-4, validating Nectin-4 as a clinical target for toxin delivery in this indication. Despite excellent data in urothelial cancer, little efficacy data are reported for EV in other Nectin-4 expressing tumors and EV therapy can produce significant toxicities in many patients, frequently leading to discontinuation of treatment. Thus, additional approaches to this target with the potential to extend utility and reduce toxicity are warranted.

Discovery and Optimization of a Synthetic Class of Nectin-4-Targeted CD137 Agonists for Immuno-oncology.

CD137 (4-1BB) is a co-stimulatory receptor on immune cells and Nectin-4 is a cell adhesion molecule that is overexpressed in multiple tumor types. Using a series of poly(ethylene glycol) (PEG)-based linkers, synthetic bicyclic peptides targeting CD137 were conjugated to targeting Nectin-4. The resulting bispecific molecules were potent CD137 agonists that require the presence of both Nectin-4-expressing tumor cells and CD137-expressing immune cells for activity.

Multisite randomised controlled trial of trauma-focused cognitive behaviour therapy for psychosis to reduce post-traumatic stress symptoms in people with co-morbid post-traumatic stress disorder and psychosis, compared to treatment as usual: study protocol for the STAR (Study of Trauma And Recovery) trial.

Background: People with psychosis have high rates of trauma, with a post-traumatic stress disorder (PTSD) prevalence rate of approximately 15%, which exacerbates psychotic symptoms such as delusions and hallucinations. Pilot studies have shown that trauma-focused (TF) psychological therapies can be safe and effective in such individuals. This trial, the largest to date, will evaluate the clinical effectiveness of a TF therapy integrated with cognitive behaviour therapy for psychosis (TF-CBTp) on post-traumatic stress symptoms in people with psychosis.

BT7480, a novel fully synthetic tumor-targeted immune cell agonist™ ( TICA™) induces tumor localized CD137 agonism.

Background: CD137 (4-1BB) is an immune costimulatory receptor with high therapeutic potential in cancer. We are creating tumor target-dependent CD137 agonists using a novel chemical approach based on fully synthetic constrained bicyclic peptide () technology. Nectin-4 is overexpressed in multiple human cancers that may benefit from CD137 agonism.