We Use Gene Editing to Modify the Immune System for Attenuating Severe Chronic Diseases.
WE ARE LEMPO AND WE WILL MOVE THE WORLD
Why?
We believe that science must assure that the increase in human longevity is accompanied by an improvement in the ability to maintain good quality of life to enjoy the additional years.
How?
Utilizing cutting edge bio-technologies for developing treatments that modify the immune system to attenuate the progression of chronic diseases.
What?
Preclinical studies have shown that high MPO protein level either cause or aggravate Pulmonary
Arterial Hypertension (PAH). We use gene editing to modify the MPO expression in neutrophils
and eliminate its negative effect on PAH.
(At a later stage, we will apply this treatment to address
Alzheimer's Disease, Multiple
Sclerosis and other severe
chronic disease).
Give me a lever and a place to stand
and I will move the world
~Archimedes
THE SCIENCE
Neutrophils
White blood cells. Act as first responders of the immune system against pathogens.
Myeloperoxidase (MPO)
A powerful "chemical bomb" - a peroxidase enzyme. Carried by neutrophils to the area of invasion, generating HOCl acid for killing the pathogens.
MPO - A friend and a Foe
The Good - Effective bacterial killing;
The Bad - Implicated in diseases associated with chronic
non-microbial pathological processes;
The Consensus - For specific, severe, life threatening diseases, MPO suppression is beneficial.
MPO Deficiency
MPO Deficiency is a known, naturally occurring condition, existing in 1:2000 people and is considered clinically insignificant.
Myeloperoxidase role is considered redundant to other
bacteria fighting mechanisms.
MPO is secreted from neutrophils and catalyzes the formation of the toxic substance hypochlorous acid (HOCl) as well as other oxidative substances resulting in severe oxidative damage. Upon release, MPO causes multiple and non-specific damage to pathogens as well as to the surrounding tissue.
PULMONARY ARTERIAL HYPERTENSION
Overview
Pulmonary Arterial Hypertension (PAH) is a rare,
progressive disorder, primarily affecting women, with no cure and leading to poor life expectancy.
The condition begins with progressive narrowing of arteries between the heart and the lungs, making it difficult for blood to flow through them. As a result, the heart tries to compensate by pumping harder, the right side of the heart becomes stressed and eventually fails.
and Lungs
Current treatments
Current medications focus each on a specific disease progression pathway, aiming to bring the substance back into balance. They do not provide cure but a temporary relief of PAH damages and symptoms. These pathways include:
Endothelin receptor (ET) antagonists (ERAs)
Prostacyclin analogues
Phosphodiesterase (PDE) type 5 inhibitors
Activators of soluble guanylyl cyclase (sGC)
Combination therapy has shown to be effective for patients (especially those in “low risk” criteria). Yet, a substantial proportion of them experience clinical worsening despite the combination therapy.
Following this inadequate clinical response and after advancing from a low risk criteria into moderate or high risk, patients are being put on the waiting list for lung transplant as a last resort.
The underlying pathological hallmarks of PAH include pulmonary arterial endothelial cell (EC) dysfunction, pulmonary artery EC and smooth muscle cell (SMC) proliferation, excessive vasoconstriction, RV hypertrophy, fibrosis & inflammation and in-situ thrombosis.
MPO IMPLICATED IN WORSENING PULMONARY ARTERIAL HYPERTENSION
MPO causative role in PAH
MPO has been implicated in aggravating PAH in a multitude of ways, in some of them directly causing the damage and in others taking part in the chain of events leading to damage creation.
Oxidative damage
Via generation of reactive oxygen species (ROS), activation of vascular Rho-kinase and consumption of nitric oxide (NO) causing
smooth muscles vasoconstriction and hypoxia-induced vascular remodeling.
Physical damage
By its cationic charge, directly leading to physical collapse of the inner layer of the artery wall (Endothelial Glycocalyx -EG) and damaging its integrity.
Indirect damage
By binding to red blood cells (RBCs), MPO is transported to remote sites and affects endothelial function as well as systemic vascular resistance and vascular deformation. Also, in certain pathological conditions, MPO has been shown to cause deformation of RBCs.
MPO is required for regulating the formation of Neutrophil Extracellular Traps (NETosis), a neutrophil cell death characterized by secretion of large web-like structures. NET formation is associated with the severity of aortic stenosis, trigger of angiogenesis and creation of blood clots.
Physically damaged Endothelial Glycocalyx
Wiesinger A, Peters W, Chappell D, Kentrup D, Reuter S, et al. (2013) Nanomechanics of the
Endothelial Glycocalyx in Experimental Sepsis. PLOS ONE 8(11): e80905.
MPO is required for NETosis formation:
Neutrophils from donors who are completely deficient in MPO do not form NETs, indicating that MPO is required for NET formation. In contrast, neutrophils from partially MPO-deficient donors make NETs, and pharmacological inhibition of MPO only delays and reduces NET formation (Blood. 2011;117(3): 953-959).
MPO DEFICIENCY ATTENUATES
PULMONARY ARTERIAL HYPERTENSION
Mounting evidence show the value of MPO Deficiency in attenuation of PAH progression. Experiments in various animal models revealed the following benefits:
-
Protects from hyper-proliferation.
-
Preserves endothelial functions.
-
Prevents reduction of endothelial glycocalyx (EG) thickness
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Inhibits excessive vasoconstriction and smooth muscle damage.
-
Attenuates pulmonary vascular remodeling.
-
Reduces inflammation angiogenesis and fibrosis.
Upon hypoxia, MPO-Deficient mice exhibited a profoundly reduced Right Ventricular Pressure (systolic) in comparison with WT mice.
JCI Insight. 2018;3(11):e97530. 10.1172/jci.insight.97530
LEMPO INNOVATION
For people suffering from diseases aggravated by MPO damages, MPO-001 (Lempo treatment) modifies the MPO in the neutrophils, creating a condition of MPO Deficiency.
MPO-001 is a one-time treatment for permanently modifying the MPO protein in neutrophils using ex-vivo CRISPR / Cas9 for knocking out the MPO gene in CD34+ stem cells. MPO-001 is delivered by an autologous Hematopoietic Stem Cell Transplantation.
The procedure
1. At the hospital
-
Stem cells collected from the patient via mobilization and apheresis
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Backup cells kept at site as a safety measure
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Cells shipped to manufacturing facility
2. At Lempo's manufacturing facility
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CD34+ cells isolated
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Ribonucleoprotein (RNP)-mediated CRISPR genome editing delivered via electroporation
3. At Lempo's manufacturing facility
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MPO knocked out stem cells cryopreserved and tested
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Once approved, cells are released back to the hospital
4. At the hospital
-
Cryopreserved cells received and stored until infusion
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Patient goes through myeloablative conditioning
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MPO-001 thawed and infused
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Patient monitored for engraftment and immune reconstitution
LEMPO THERAPEUTICS ROADMAP
Following completion of phase I/II studies in PAH and in parallel to completing the work needed for receiving marketing authorization, Lempo plans to commence work on advancing the use of its treatment for additional indications, including Multiple Sclerosis, Alzheimer Disease and others.
The company is actively looking for strategic partners for achieving this goal.
Validated indications for MPO deficiency
THE TEAM
Lempo employs a collaborative work model for its therapeutic programmes, working with clinicians and researchers at leading academic centres. Prof. Ben-Zion Garty, co-founder of Lempo and a renowned immunologist, explained, “Lempo works with carefully chosen research labs, led by worldwide experts in specific aspects of our program, covering CRISPR, HSCT, MPO deficiency, and PAH. Jointly, we are able to accelerate the program towards an optimal treatment”.
The operation is managed by a team of experienced professionals directing the distributed programmes. This model ensures high quality, fast pace and capital efficiency.
Leadership
Oren Glanz - CEO
20+ years as serial entrepreneur, and CEO
Senior lecturer at the Israeli
Technion Institute
Recognized in 2012 as 1 of 100 most influential people in Israel
Dr. Anat Kahana - CSO
The inventor of Lempo MPO-001
Molecular Biologist – Tel Aviv
University, Bar-Ilan university and Weizmann institute of Science
Translational Medical Researcher
Prof. Ben-Zion Garty
Clinical Research
MD Pediatric Immunology
Clinician - Allergies and
Immunodeficiency
Former head of children ward in Schneider Children Hospital
First physician in Israel to treat pediatric PAH
Full Professor at the Tel Aviv University medical school
Cooperating Labs
Prof. Donald B. Kohn, MD
Department of Microbiology, Immunology & Molecular Genetics University of California, Los Angele.
Broad Stem Cell Research Center, UCLA
Expertise: Gene Editing, Stem cells therapies, bone marrow transplant
Prof. Stephan Rosenkranz, MD
Head of the Pulmonary
Hypertension (PH) Center at the University of Cologne,
Germany, and Cologne
Cardiovascular
Research Center (CCRC)
Expertise: Pulmonary Arterial Hypertension, MPO in CVD
Prof. Daniel Offen, PhD
Head of Translational
Neuroscience Lab, Dept. of
Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel Aviv University.
Expertise:
Neurological diseases and
MPO
Scientific Advisory
Prof. William M. Nauseef,
MD
Inflammation program, Iowa
University Center for
Immunology and Immune-
based Diseases.
Expertise: MPO and MPO
Deficiency
Dr. Moshe Yeshurun, MD
Director of Bone Marrow Transplantation Department, Beilinson Hospital, Rabin Medical Center.
Expertise: Bone marrow and stem cell transplantation
Prof. Yochai Adir, MD
Head of the Pulmonary Division,
Carmel Medical Center,
Faculty of Medicine, The
Technion Institute of
Technology, (Haifa, Israel), Chair of Israel Society of
Expretise: Pulmonary
diseases, Pulmonary
Arterial Hypertension
A life mission, Not a venture
Diagnosed with Multiple Sclerosis (MS) and confined to a wheelchair because of it, Oren Glanz, CEO took interest in new therapies to treat diseases like his. One day he was approached by his friend, Dr. Anat Kahana, that worked with Prof. Ben-Zion Garty on MPO and its role in diseases including MS. This was the beginning of the journey of Lempo which was established in 2017.
Once ready for treating humans, Oren plans to make use of MPO-001, hoping to be able to walk again.
PARTNERSHIPS AND COLLABORATIONS
Lempo main goal is to advance its treatment to the market as fast as can be done and as safe as possible.
For that purpose, Lempo is fortunate and proud to be working with the following partners:
Looking to accelerate its pace and broaden its reach the company is constantly on the look for additional opportunities to cooperate in research, development and commercialization, both for the PAH treatment as well as for additional indications, especially Multiple Sclerosis and Alzheimer's Disease.
To learn more about Lempo Therapeutics and opportunities for partnering & collaborations, please complete the form below.
CONTACT US
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