eNamptor (enamptcumab) / Aqualung Therap - LARVOL DELTA

Safety, Tolerability and Pharmacokinetics of the eNAMPT-Neutralizing ALT-100 Mab in Healthy Volunteers. (PubMed, J Clin Res Clin Trials) - "The mean maximum mAb plasma concentration (Cmax) and mAb elimination half-life (T1/2) all increased in a dose-related manner between 0.4 mg/kg (17 days) and 4 mg/kg (27 days). Single intravenous ALT-100 mAb doses are well tolerated in healthy participants with dose proportional PK and elimination half-life."

Journal • PK/PD data • Fibrosis • Hematological Disorders • Oncology • TLR4

Targeting glioma tumor microenvironment by specific neutralization of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) using ALT-100, a novel humanized monoclonal antibody (SNO 2024) - P2 | "This is the first report of ALT-100-mediated eNAMPT neutralization in gliomas and demonstrates profound effects on the tumor and its microenvironment. Given that ALT-100 is in phase 2 trials (NCT05938036) against ARDS, data from our studies can potentially accelerate translating ALT-100-mediated eNAMPT neutralization to treat gliomas."

Biomarker • IO biomarker • Tumor microenvironment • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • NAMPT

Study of Safety and Efficacy of ALT-100mAb in Participants With Moderate/Severe ARDS (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Aqualung Therapeutics Corp. | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Aug 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Enrollment open • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases • NAMPT

Study of Safety and Efficacy of ALT-100mAb in Participants With Moderate/Severe ARDS (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Aqualung Therapeutics Corp. | Initiation date: Jul 2023 ➔ Nov 2023

Trial initiation date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases • NAMPT

First-In-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALT-100 (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Aqualung Therapeutics Corp. | Active, not recruiting ➔ Completed

Trial completion • Mood Disorders

Study of Safety and Efficacy of ALT-100mAb in Participants With Moderate/Severe ARDS (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Aqualung Therapeutics Corp.

New P2 trial • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases • IL6

First-In-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALT-100 (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Aqualung Therapeutics Corp. | Recruiting ➔ Active, not recruiting

Enrollment closed • Mood Disorders

Aqualung Therapeutics Corp. Awarded $4.8M Dollars From National Institute of Health (NIH) To Develop the ALT-100 Monoclonal Antibody for Pulmonary Arterial Hypertension and Inflammatory Bowel Disease (Yahoo News) - "Aqualung Therapeutics...has been awarded two 3-year NIH FAST-TRACK AWARDS [R42DK135208; R42HL160422) to support development of ALT-100, a humanized monoclonal antibody (mAb) therapy for the chronic indications of Pulmonary Arterial Hypertension (PAH) and Inflammatory Bowel Disease (IBD). The ALT-100 mAb targets the inflammation-inducing damage-associated molecular pattern protein eNAMPT, and is currently in Phase 1A human safety trials....These two NIH STTR Awards will confirm the efficacy of subcutaneously delivered ALT-100 mAb as well as appropriate dosing schedules in both IBD and PAH pre-clinical animal models, and provide financial support for the IND-enabling PK, PD and toxicology studies."

Financing • Immunology • Inflammatory Bowel Disease

First-In-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALT-100 (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Aqualung Therapeutics Corp. | Not yet recruiting ➔ Recruiting

Enrollment open • Mood Disorders

First-In-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALT-100 (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Aqualung Therapeutics Corp.

New P1 trial • Mood Disorders

Aqualung Therapeutic’s ALT-100 Monoclonal Antibody Cited as A Novel Therapeutic for Lung Fibrosis (Digital Journal) - "Dr. Rosas commented that 'The intimate interplay between fibrotic pathways and inflammatory pathways is well established. The study by Garcia and the Aqualung team using a lung radiation mouse model, strongly supports eNAMPT as a key, highly druggable target to reduce eNAMPT/TLR4-driven inflammatory cascades involved in tissue fibrosis....While additional studies are warranted using complementary models of lung fibrosis and possibly in large animals, ALT-100 appears to be a potentially effective strategy to attenuate inflammation and the severity of fibrosis in the lung and other organs as well.'"

Media quote • Idiopathic Pulmonary Fibrosis

Preclinical studies show Aqualung Therapeutic’s eNAMPT- targeting ALT-100 mAb to reduce severity of aggressive prostate cancer (Yahoo Finance) - "Preclinical prostate cancer (PCa] studies published in the December 17th, 2021 issue of Pharmaceuticals show Aqualung Therapeutic's ALT-100 mAb to significantly improve overall survival and to reduce distal metastases in SCID mice implanted with human prostate cancer (PCa] cells....By injecting an anti-eNAMPT neutralizing antibody such as ALT-100, this study demonstrated the potential to delay the switch to aggressive PCa and potentially prevent PCa progression and metastases."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

[VIRTUAL] Validating a scoring system for immunoglobulin unresponsiveness in high risk kawasaki disease (WSMRF 2021) - "Criteria to qualify for the high risk protocol included: age ≤ 12 months or ≥ 8 years, Z score of LAD or RCA ≥ 3.5, or CRP ≥ 15 mg/dL with one additional finding of the following WBC >20,000, Platelet count 100...A patient will be considered unresponsive to IVIG therapy if they received additional therapy (IVIG, steroids, infliximab or another biologic) or the Z-score for the RCA ≥ 3.5 or LAD ≥ 3.5...Conclusions After the implementation of the high-risk KD protocol, there was a significant improvement in the responsiveness to IVIG. We believe that early steroid administration in these high-risk patients can prevent the need for additional therapy."

Endothelial eNAMPT Amplifies Preclinical Acute Lung Injury: Efficacy of an eNAMPT-Neutralising mAb. (PubMed, Eur Respir J) - "These findings highlight both the role of EC-derived eNAMPT and the potential for biologic targeting of the eNAMPT/TLR4 inflammatory pathway. In combination with predictive eNAMPT biomarker and NAMPT genotyping assays, this offers the opportunity to identify high-risk ARDS subjects for delivery of personalised medicine."

IO Biomarker • Journal • Preclinical • Acute Lung Injury • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • IL6 • NAMPT

[VIRTUAL] JNK BINDING AND PHOSPHORYLATION SITES ON THE CYTOPLASM- FACING DOMAIN OF MITOCHONDRIAL SAB (SH3BP5) ARE REQUIRED FOR ACETAMINOPHEN (APAP) HEPATOTOXICITY (AASLD 2020) - "However, expression of docking site mutated form of SAB lead to marked resistance to histological necrosis and ALT elevation (ALT 100±10 versus 12,900 ± 50 U/L p<0.05 mutant vs WT SAB n=3 per group) at 24 hours after APAP and completely suppressed JNK activation at 2h after APAP... Both the C-terminal SAB binding site and a nearby single phosphorylation site are required for the interaction of P-JNK and SAB to activate intramitochondrial signaling pathway which interferes with mitochondrial function and increases production and release of ROS to sustain the cytoplasmic JNK activation pathway and oxidative stress- induced necrosis."

Hepatology • Liver Failure • MAPK8

A Randomized Controlled Trial of Intravenous N-acetylcysteine in the Management of Anti-tuberculosis Drug-Induced Liver Injury. (PubMed, Clin Infect Dis) - "NAC did not shorten time to ALT&100 U/L in participants with AT-DILI, but significantly reduced length of hospital stay. NAC should be considered in management of AT-DILI."

Clinical • Journal • Hepatology • Infectious Disease • Liver Failure • Pain • Tuberculosis

[VIRTUAL] Rare Case of Donor Transmission of Hepatitis a Virus in Two Kidney Transplant Recipients (ATC 2020) - "Patient B had low level transaminitis (~ALT 100 U/L) at 4wk post-DDKT but remained asymptomatic, until 3months post-DDKT when he developed symptomatic acute hepatitis (pruritus, ~ALT 1200 U/L), work-up also demonstrated acute HAV... The SOT recipients are high risk of symptomatic disease with transmission and pre-transplant vaccinations should be universally employed. While HAV is not a widespread public health disease in US, the incidence is rising and enhanced screening for donors in HAV outbreak area should be considered."

Clinical • Dermatology • Fatigue • Immunology • Pruritus • Transplantation