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.

Netosis_with_Explosion_Small.gif

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 

  • 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. https://doi.org/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

  • Backup cells kept at site as a safety measure

  • Cells shipped to manufacturing facility

2. At Lempo's manufacturing facility

  • CD34+ cells isolated

  • Ribonucleoprotein (RNP)-mediated CRISPR genome editing delivered via electroporation

3. At Lempo's manufacturing facility

  • MPO knocked out stem cells cryopreserved and tested

  • Once approved, cells are released back to the hospital

4. At the hospital

  • Cryopreserved cells received and stored until infusion

  • Patient goes through myeloablative conditioning

  • MPO-001 thawed and infused

  • 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

visit website

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

visit website

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

visit website

Scientific Advisory

Prof. William M. Nauseef,

MD

Inflammation program, Iowa

University Center for

Immunology and Immune-

based Diseases.

Expertise: MPO and MPO

Deficiency

visit website

Dr. Moshe Yeshurun, MD

Director of Bone Marrow Transplantation Department, Beilinson Hospital, Rabin Medical Center.

Expertise: Bone marrow and stem cell transplantation

visit website

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

Pulmonology.

Expretise: Pulmonary

diseases, Pulmonary

Arterial Hypertension

visit website

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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© 2020 Lempo Therapeutics Ltd.

O: +972-54-4746740

F : +972-77-3179663

info@lempo-tx.com

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