- Investment will support investigation of Mission's small
molecule drug MTX325 in patients with early-stage Parkinson's
disease
- Marks latest step in Mission's relationship with The
Michael J. Fox Foundation (MJFF), after MJFF awarded Mission
preclinical research grants in 2017 and 2021, and first with
Parkinson's UK
- Comes as promising early data from healthy volunteers show
MTX325 has a good safety profile, pharmacokinetics and CNS
penetration
CAMBRIDGE, England, July 2, 2024
/PRNewswire/ -- Mission Therapeutics ("Mission" or the "Company"),
a clinical-stage biotech developing first-in-class therapeutics
targeting mitophagy, has been awarded $5.2
million from The Michael J. Fox Foundation for Parkinson's
Research (MJFF) and Parkinson's UK. The funding will help advance
Mission's potential disease-modifying treatment for Parkinson's,
MTX325.
MTX325 is a potent, selective, small molecule brain-penetrant
USP30 inhibitor, which is designed to protect dopamine-producing
neurons by improving mitochondrial quality and function. The
funding will support a 28-day dosing of MTX325 in patients with
early-stage Parkinson's disease (PD), as part of Mission's ongoing
MTX325 Phase I program. Patient dosing is expected to start early
in 2025. The aims are to understand MTX325's safety, tolerability,
pharmacokinetic profile and CNS penetration in PD patients, as well
as observing effects on relevant mechanisms and disease biology
biomarkers.
Mission started its multi-part, adaptive Phase I first-in-human
clinical trial of MTX325 in March, beginning with a single
ascending dose stage in healthy volunteers. Initial investigations
of MTX325's CNS penetration ability in these healthy volunteers
have yielded positive results. The multiple ascending dose stage of
the study was initiated last month (June).
Anker Lundemose, Chief Executive Officer, Mission
Therapeutics, said: "This significant grant, from two of
the world's leading Parkinson's disease organisations, underlines
the huge potential of MTX325 as a disease-modifying treatment for
this terrible neurodegenerative illness. It also represents a major
endorsement of our mitophagy strategy in human diseases including
PD."
Dr Paul Thompson, Chief
Scientific Officer, Mission Therapeutics, said: "We have
already made excellent progress in healthy volunteers with
preliminary data from the ongoing clinical trial showing that
MTX325 has a good single dose safety profile, pharmacokinetics and
CNS penetration. We look forward to starting the PD patient part of
the trial in the new year, which this generous funding from MJFF
and Parkinson's UK is helping to support."
Katharina Klapper, director of
clinical research at MJJF, said: "Mission
Therapeutics has made great advances in the understanding of how
mitochondrial health can play a pivotal role in the development of
Parkinson's disease in recent years. We look forward to seeing
the results of the MTX325 trial."
Dr Arthur Roach, Director of
the Parkinson's Virtual Biotech at Parkinson's UK,
said: "We are delighted to be working with Mission Therapeutics
to help fund this vital, UK-based clinical trial. Disease-modifying
treatments are one of the great hopes of people with Parkinson's.
We now know that mitochondria play a crucial role in the
development of Parkinson's, so addressing mitochondrial problems
could have far-reaching benefits for those living with the
condition."
Parkinson's is a neurodegenerative disease which affects around
10 million people globally. It is characterised by low levels
of the neurotransmitter dopamine and there are currently no
approved disease-modifying treatments for the condition.
MTX325 protects dopamine-producing neurons by enhancing a
cellular quality control process called mitophagy, in which faulty
mitochondria are tagged and then removed. MTX325 does this by
inhibiting USP30, a deubiquitylating enzyme (DUB) which impedes
normal mitophagy.
Last December scientists at Cambridge
University, Harvard University
and Mission Therapeutics published a key academic paper outlining
preclinical research on USP30 and MTX325 in the journal Nature
Communications. The paper detailed knockout
mouse model data which, the authors said, provided strong
experimental evidence supporting the thesis that MTX325 can modify
the course of PD by targeting USP30.
A growing body of scientific evidence has linked a build-up of
dysfunctional mitochondria in cells to a range of diseases
including Parkinson's, 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:
https://www.nature.com/articles/s41467-023-42876-1
About Parkinson's UK and the Parkinson's Virtual
Biotech
We are Parkinson's UK. Here for everyone affected by the
condition. Funding research into the most promising treatments,
taking us closer to a cure every day. Fighting for fair treatment
and better services.
In 2017, we founded the Parkinson's Virtual Biotech. A
groundbreaking global movement to deliver life-changing new
treatments in years not decades. It uses cutting edge biological
and chemical research to come up with new treatments. Driven by
people with Parkinson's, not profit, it adapts successful methods
from the biotech and business worlds to deliver new treatments
faster.
The Parkinson's Virtual Biotech is now an international programme
in partnership with the Parkinson's Foundation. We believe we'll
get a cure faster by collaborating, not competing. The innovative
approach is working. The next treatment is closer than ever.
Further information, advice and support is available on our
website, www.parkinsons.org.uk
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SOURCE Mission Therapeutics