PT150 / The Pop Test & Palisades Therap - LARVOL DELTA

NOT JUST VOLUME OVERLOAD: CARDIAC TAMPONADE MIMICKING DYSPNEA IN AN ESRD PATIENT ON HEMODIALYSIS (CHEST 2025) - "Her medical history included post-transplant lymphoproliferative disorder (PTLD-DLBCL), atrial fibrillation managed with a Watchman device May 2024 (on clopidogrel), Crohn's disease, and recent right knee replacement two weeks prior...The hemorrhagic effusion was attributed to coagulopathy given elevated INR >15, PT 150, and PTT 124... This case highlights the critical importance of a tailored approach to managing dyspnea in ESRD patients, particularly those presenting with hypotension during or after dialysis. It also serves as a reminder for clinicians managing ESRD patients: dyspnea is not synonymous with volume overload. Maintaining a high degree of suspicion, performing comprehensive clinical assessment, and leveraging advanced diagnostic tools like POCUS are paramount in ensuring that this life-threatening condition is not overlooked."

Clinical • Anemia • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Crohn's disease • Diffuse Large B Cell Lymphoma • Gastroenterology • Hematological Disorders • Hypotension • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Musculoskeletal Diseases • Nephrology • Orthopedics • Pulmonary Disease • Renal Disease

Initial Study Sesting Efficacy and Tolerability of PT150 for PTSD in Veterans (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: San Diego Veterans Healthcare System

New P2 trial • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Pharmacokinetic Interactions Between Ethanol and PT150, a Selective Glucocorticoid Receptor Antagonist, in Healthy Volunteers. (PubMed, J Addict Med) - "These data suggest that coadministration of PT150 and alcohol does not produce significant pharmacokinetic interactions, supporting the feasibility of evaluating PT150 in future clinical trials for alcohol use disorder."

Journal • PK/PD data • Addiction (Opioid and Alcohol)

PT150 Drug for Use in Alcohol Use Disorder (clinicaltrials.gov) - P1 | N=34 | Recruiting | Sponsor: Pop Test Oncology LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol)

The "Straight Line TEG": Confirmation and Management of a New-Onset Coagulopathy Prior to Reperfusion during a Liver Transplant (IARS-SOCCA 2025) - "The coagulation panel also confirmed the profound coagulopathy (INR=20.38, fibrinogen 50, aPTT>150, PT>150, D-dimer 58,522)...A heparinase TEG sent shortly after the portal vein was unclamped showed a resolution of the fibrinolysis, but the tracing remained nearly flat (R=43.8 K=undetectable α=0.9 MA=2.2 Ly30=0.0).The patient received a total of 18 pRBC, 25 FFP, 4 platelets, 4 cryoprecipitate, 500 units of PCC, 2g fibrinogen concentrate, 1.2L of cell saver, TXA and DDAVP...This case highlights the utility of TEGs in diagnosing and treating unexpected, severe coagulopathies. In addition to real-time data, TEG is a more reliable indicator of coagulation than traditional labs in patients with ESLD1. While there are multiple case reports documenting coagulopathies during liver transplant, including ones with "straight line" TEGs2,3, the development of a new coagulopathy prior to the reperfusion phase, in the absence of significant resuscitation, is rare."

Cardiovascular • Fibrosis • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Nephrology • Renal Disease • Septic Shock • Thrombosis • Transplantation

PT150 Drug for Use in Alcohol Use Disorder (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Pop Test Oncology LLC

New P1 trial • Addiction (Opioid and Alcohol)

Neuroprotective Efficacy of the Glucocorticoid Receptor Modulator PT150 in the Rotenone Mouse Model of Parkinson's Disease. (PubMed, Neurotoxicology) - "Ultimately, PT150 treatment reduced the loss of DAn cell bodies in the SN, but not the striatum, and prohibited intra-neuronal accumulation of α-syn. Together, these data indicate that PT150 effectively reduced SN pathology in the rotenone mouse model of PD."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Pop Test Oncology LLC | Recruiting ➔ Completed

Trial completion • Addiction (Opioid and Alcohol)

Synergy between interleukin-1β, interferon-γ and glucocorticoids to induce TLR2 expression involves NF-κB, STAT1 and GR. (PubMed, Mol Pharmacol) - "In human A549 epithelial and primary human bronchial epithelial cells (pHBECs), toll-like receptor (TLR) 2 mRNA and protein were supra-additively induced by interleukin-1β (IL1B) plus dexamethasone (IL1B+Dex), interferon-γ (IFNG) plus dexamethasone (IFNG+Dex) and IL1B plus IFNG plus dexamethasone (IL1B+IFNG+Dex)...Using the A549 cell model, TLR2 induction by IL1B+IFNG+Dex was antagonized by Org34517, a competitive GR antagonist...This effect involved positive combinatorial interactions between NF-κB/p65, GR and JAK-STAT1 signalling to synergistically upregulate TLR2 expression. Thus, synergies involving glucocorticoid-enhancement of TLR2 expression may occur in the immunopathology of glucocorticoid-resistant inflammatory diseases, including severe asthma."

IO biomarker • Journal • Asthma • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • IFNG • IL1B • NFKB1 • NR3C1 • STAT1 • TLR2

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Pop Test Oncology LLC | Trial completion date: Jul 2023 ➔ Oct 2023 | Trial primary completion date: Jul 2023 ➔ Oct 2023

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

PT150 blocks the rewarding properties of ethanol and attenuates ethanol-induced reduction of egg laying in Coturnix quail. (PubMed, Psychopharmacology (Berl)) - "These findings suggest repeated ethanol pairings with visual cues can produce a CPP. Furthermore, pretreatment of PT150 may be a potential pharmacotherapy for blocking the rewarding properties of ethanol and may enhance egg production in female quail treated with ethanol."

Journal • Addiction (Opioid and Alcohol)

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Pop Test Oncology LLC | Trial completion date: Jan 2023 ➔ Jul 2023 | Trial primary completion date: Jan 2023 ➔ Jul 2023

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Pop Test Oncology LLC | Trial completion date: Apr 2022 ➔ Jan 2023 | Trial primary completion date: Mar 2022 ➔ Jan 2023

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress. (PubMed, Exp Clin Psychopharmacol) - "While males self-administered more than females overall, PT150 decreased intake in males and increased intake in females, thus negating the sex difference. Although PT150 may serve as an effective treatment for reducing the risk of OUD following early-life stress in males, further work is needed to determine the mechanism underlying the differential effects of PT150 in males and females."

Journal • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Substance Abuse

A Novel Glucocorticoid and Androgen Receptor Modulator Reduces Viral Entry and Innate Immune Inflammatory Responses in the Syrian Hamster Model of SARS-CoV-2 Infection. (PubMed, Front Immunol) - "Phylogenetic analysis of AR and GR revealed a high degree of sequence identity maintained across multiple species, including humans, suggesting that the mechanism of action and therapeutic efficacy observed in Syrian hamsters would likely be predictive of positive outcomes in patients. PT150 is therefore a strong candidate for further clinical development for the treatment of COVID-19 across variants of SARS-CoV-2."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CD4 • IL6 • TMPRSS2

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1; N=10; Recruiting; Sponsor: Pop Test Oncology LLC; Not yet recruiting ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol)

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1; N=10; Not yet recruiting; Sponsor: Pop Test Oncology LLC; Trial completion date: Aug 2021 ➔ Mar 2022; Trial primary completion date: Jul 2021 ➔ Feb 2022

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Effects of the glucocorticoid receptor antagonist PT150 on stress-induced fentanyl seeking in male and female rats. (PubMed, Psychopharmacology (Berl)) - "The glucocorticoid antagonist PT150 reduces shock-induced fentanyl seeking, suggesting it may be effective against stress-induced relapse, although the sex difference in response may need further exploration."

Journal • Preclinical

A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers. (PubMed, Sci Rep) - P1 | "These data show that administration of PT150 with concurrent alcohol use is safe and well-tolerated. This study supports a future pharmacokinetic interaction study between PT150 and alcohol.Trial Registration ClinicalTrials.gov Identifier: NCT03548714."

Clinical • Journal • PK/PD data • CNS Disorders • Depression • Psychiatry

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1; N=10; Not yet recruiting; Sponsor: Pop Test Oncology LLC; Trial completion date: Mar 2021 ➔ Aug 2021; Initiation date: Nov 2020 ➔ Apr 2021; Trial primary completion date: Feb 2021 ➔ Jul 2021

Trial completion date • Trial initiation date • Trial primary completion date • Addiction (Opioid and Alcohol)

Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2. (PubMed, Cell Cycle) - "We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity. Given that hypercortisolemia is now suggested to be a significant co-factor for COVID-19 progression, we also postulate an additive role for its potent immunomodulatory effects through systemic antagonism of cortisol."

Clinical • Journal • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1; N=10; Not yet recruiting; Sponsor: Pop Test Oncology LLC; Trial completion date: Dec 2020 ➔ Mar 2021; Initiation date: May 2020 ➔ Nov 2020; Trial primary completion date: Aug 2020 ➔ Feb 2021

Trial completion date • Trial initiation date • Trial primary completion date • Addiction (Opioid and Alcohol)

[VIRTUAL] Pan-cancer analysis to identify a novel class of glucocorticoid and androgen receptor antagonists with potent anti-tumor activity. (ASCO 2020) - "In addition, both PT150 and PT157 significantly increased nab-paclitaxel sensitivity in nab-paclitaxel-resistant isogenic PDAC cells. Our work has identified previously undescribed mechanisms of oncogenesis in several cancer types, as well as an efficacious class of novel compounds with the potential to inhibit them. Research Funding: Palisades Therapeutics/Pop Test Oncology LLC"

Pan Tumor • Brain Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Meningioma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Solid Tumor • AR

Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study) (clinicaltrials.gov) - P1; N=10; Not yet recruiting; Sponsor: Pop Test Oncology LLC

New P1 trial