USP30

The acquisition enhances the portfolio of Aditxt in precision diagnostics and infectious disease treatment. Credit: Gorodenkoff / Shutterstock.com. Aditxt has announced a definitive agreement under which its subsidiary, Adivir, will acquire complete issued and outstanding Class A common shares of biopharmaceutical company Appili Therapeutics. The move enhances Aditxt’s portfolio and creates synergies with its existing programmes, particularly in precision diagnostics. Founded in 2015, Appili developed the Food and Drug Administration-approved LIKMEZ (ATI-1501). LIKMEZ is a reformulated version of the antibiotic metronidazole that improves patient experience and compliance by making the medication easier to swallow and better tasting. Appili licensed the manufacturing and commercialisation rights of the product in the US and other selected territories to Saptalis Pharmaceuticals. See Also: Forma Therapeutics gets grant for USP30 inhibitor compounds for medical use Dyne Therapeutics gets grant for muscle-targeting complex inhibiting DUX4 expression with oligonucleotide payload Appili is also advancing ATI-1701, a live attenuated vaccine for Francisella tularensis. The US Department of Defense has supported the ATI-1701 biodefence programme with $14m non-dilutive funding to progress the vaccine’s development. Another key asset in Appili’s portfolio is ATI-1801, a topical formulation for cutaneous leishmaniasis. The product, which contains paromomycin, offers a more patient-friendly treatment option for this painful and disfiguring disease. The acquisition will aid Aditxt in bolstering its portfolio and integrating precision diagnostics with tailored treatment strategies. The closure of the acquisition will occur in the third quarter of 2024. Aditxt co-founder, chairman and CEO Amro Albanna stated: “The acquisition of Appili would represent another step in Aditxt’s journey towards advancing promising innovations in health. “Our mission is to accelerate some of the most promising health innovations, like those developed by Appili, to reach their full potential and to have a lasting impact. “By integrating Appili’s proven expertise and diverse portfolio in the infectious disease and biodefence domain, Aditxt can substantially contribute to advancing public health solutions.”

Eisai’s Leqembi 100mg IV injection is approved to treat patients with early Alzheimer’s disease. Credits: joshimerbin/Shutterstock.com As Eli Lilly’s plans for its Alzheimer’s medication donanemab get delayed , Eisai has submitted a supplemental Biologics License Application (sBLA) to the US Food and Drug Administration (FDA) in a bid to bring intravenous (IV) maintenance dosing of its drug Leqembi (lecanemab) to patients with early Alzheimer’s disease. The sBLA is supported by the observed data that was modeled from the Phase II “Study 201” trial (NCT01767311), the Phase III Clarity AD study (NCT03887455), and the open-label extension studies associated with both respective trials. As per the 31 March press announcement, patients who have completed the biweekly IV initiation phase are eligible to receive a monthly IV dose of Leqembi. The purpose of the monthly administration would be to “maintain effective drug concentration to sustain clearance of highly toxic protofibrils” which may cause further neuronal injury after amyloid beta plaque ablation. In addition to the IV maintenance therapy, Eisai is looking to gain traction for its subcutaneous (SC) version as well. While the pharma giant had originally intended to submit a rolling Biologics License Application (BLA) for its weekly SC maintenance therapy in March 2024, the company shared that it was waylaid by various agency requirements. In compliance with the agency, Eisai has submitted a Fast Track designation request that will prompt FDA action within 60 days of submission. Leqembi, a 100mg/ml IV injection indicated for the treatment of early Alzheimer’s, which is co-developed by Eisai and Biogen , gained FDA approval in July 2023. Eisai leads the drug’s global development and regulatory submissions while both Eisai and Biogen are responsible for the commercialisation of the product. See Also: Novartis gets grant for treatment of cocaine use disorder using mavoglurant Forma Therapeutics gets grant for USP30 inhibitor compounds for medical use According to GlobalData’s consensus forecasts, Leqembi is expected to yield $7.3bn in 2030. GlobalData is the parent company of Pharmaceutical Technology . Biogen recently announced the decision cut ties with its drug Aduhelm (aducanumab) , terminating its development and relinquishing the rights to the drug which has been a point of controversy for efficacy, reimbursement, and access. Unlike Leqembi whose approval history has been relatively straightforward, Aduhelm was granted accelerated approval in 2021 despite an FDA advisory panel voting against approval. Moreover, the Centers for Medicare & Medicaid Services (CMS) said that it would provide coverage for the treatment only if it was being used in clinical trial settings. For Leqembi on the other hand, CMS okayed coverage upon its traditional approval provided physicians enter patient data into CMS mandated registries.

Builds on preclinical proof-of-concept that MTX325 protects dopamine-producing brain cells by enhancing mitophagy – the process cells use to remove dysfunctional mitochondria CAMBRIDGE, England, March 21, 2024 /PRNewswire/ -- Mission Therapeutics ("Mission" or the "Company"), a clinical-stage biotech developing first-in-class therapeutics targeting mitophagy, today announces the start of a Phase I first-in-human clinical trial of MTX325, its potential disease-modifying treatment for Parkinson's Disease (PD). Around 10 million people suffer from Parkinson's Disease worldwide, including almost one million in the US and around 1.2 million in Europe – numbers that are set to increase as populations age. Mission Therapeutics has now completed dosing the first cohort of healthy volunteers in a multi-part, adaptive Phase I study evaluating safety, tolerability, pharmacokinetics and brain penetration of MTX325. Single ascending, multiple dose ascending and elderly healthy volunteer cohorts are planned in 2024, whereas Parkinson's Disease patients will be the focus of the trial in 2025. Dr Paul Thompson, PhD, Chief Scientific Officer, Mission Therapeutics, said: "The launch of this first-in-human trial is a significant step forward for Mission Therapeutics, as we look to assess the potential of MTX325 as a disease-modifying treatment for Parkinson's Disease. While existing treatments for Parkinson's can help control symptoms such as tremors, slowness of movement, and cognitive problems, none address the underlying neuronal loss which causes this devastating condition." Dr Suhail Nurbhai, Chief Medical Officer, Mission Therapeutics, said: "We are delighted to have brought this second USP30 inhibitor into clinical development. The overall objectives of this Phase I trial are to confirm the safety, tolerability and CNS penetration of MTX325, in both healthy volunteers and patients with Parkinson's Disease, and help us determine appropriate doses for future efficacy testing. We look forward to progressing this compound rapidly through initial clinical testing and aim to demonstrate its potentially beneficial clinical profile later this year." The start of the trial follows the publication of a key academic paper in the journal Nature Communications last December by scientists at Cambridge University, Harvard University and Mission Therapeutics. The paper outlined their preclinical research in mouse models, which provided strong experimental evidence supporting the thesis that MTX325 can modify the course of PD by targeting USP30. USP30 is a deubiquitylating enzyme (DUB) known to inhibit mitophagy, the process cells use to rid themselves of dysfunctional mitochondria. A growing body of scientific evidence has linked a build-up of dysfunctional mitochondria in cells to a range of diseases, including PD, Kidney Disease, Heart Failure, idiopathic pulmonary fibrosis (IPF) and Duchenne's Muscular Dystrophy (DMD). About Mission Therapeutics Mission Therapeutics is a world leader in discovering and developing novel therapeutics which promote the removal of dysfunctional mitochondria, promoting cell health and function. Mitochondria are energy producing organelles which require lifetime quality control through a ubiquitin-mediated clearance mechanism known as mitophagy. In certain situations, such as cellular stress, cell injury, and/or defects of the mitophagy process, the mitochondria can become dysfunctional and damaging to the cell, leading to reduced energy production, oxidative stress, inflammation and potentially cell death. Dysfunctional mitochondria are significant drivers of disease pathophysiology in acute kidney injury (AKI), Parkinson's Disease (PD), heart failure, Duchenne's Muscular Dystrophy, IPF, mitochondrial diseases and Alzheimer's. USP30 is a deubiquitylating enzyme that constantly removes ubiquitin from mitochondria, providing a potential brake on clearance of dysfunctional mitochondria. Mission is currently developing two small molecule drugs, MTX652 (peripheral) and MTX325 (targeting the CNS) which, through inhibition of the mitochondrial DUB enzyme USP30, will promote clearance of dysfunctional mitochondria – consequently improving overall cellular health. Mission's USP30 inhibitors MTX652 and MTX325 could potentially be used to treat any disease or condition driven by mitochondrial dysfunction. Mission is backed by blue chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital. About MTX325 and USP30 MTX325 is a potent selective central nervous system-penetrant compound designed to improve mitochondrial quality and function by enhancing mitophagy. MTX325 inhibits USP30, a deubiquitylating enzyme localised to mitochondria which is a negative regulator of mitophagy. Data from an in vivo model of Parkinson's, where USP30 was deleted through gene knockout, validate USP30 as a potential target in PD. Researchers found MTX325 produced a similar effect to gene knockout of USP30 in the same PD mouse model, further validating the approach of USP30 inhibition in PD. See the paper in Nature Communications here: SOURCE Mission Therapeutics