Horizon 2020 – AllergyVAX

Next generation allergen immunotherapy based on specifically modified recombinant hypoallergens

Desentum’s goal is to set a new industry standard on allergy treatment by developing novel immunotherapeutic hypoallergens – so-called allergy vaccines. In the AllergyVAX project, we tested a birch pollen hypoallergen DM-101 (rBet v 1 dm) in a First-in-Human clinical study to evaluate its safety and potential to induce a desired immunological effect, and to obtain a roadmap for further clinical trials. A goal in the project was also to develop a business strategy for partnering and commercialization of DM-101 and the platform technology.

Background

Allergy is a rapidly increasing, global problem that already affects 1 billion people and causes significant social and economic burden. In Europe, allergic rhinitis and asthma cause more than 100 million missed work and school days per year. Allergy is usually managed by avoiding the allergen or by medication that temporarily alleviates the symptoms.

The only disease-modifying treatment available to date is allergen immunotherapy (AIT) where long-term symptom relief is achieved by training the immune system to tolerate allergens. However, typical AIT takes 3-5 years, involves monthly injections or daily drops/tablets and has the risk of serious allergic reactions during treatment. Thus, the popularity of AIT is still relatively low compared to symptomatic drugs.

We have developed a platform technology for creating modified hypoallergens to be used in AIT. It is based on making small, highly targeted modifications to allergen proteins that reduce their ability to trigger allergic reactions during treatment without compromising their efficacy in building tolerance to natural allergens. With these modified hypoallergens, we expect to shorten the injectable AIT treatment from dozens of injections over 3 years to just 3-6 injections over a few months. From the clinically important major birch pollen allergen Bet v 1 we have created DM-101 hypoallergen. In preclinical tests it has shown 100-fold reduction in histamine release compared to natural allergens and induced similar immunological responses in mice that are desired in human AIT.

Project tasks and objectives

In the AllergyVAX project we tested DM-101 for maximum tolerated dose and immunogenicity in allergic patients in a First-in-Human clinical study. The project aimed to facilitate a seamless transition to further clinical development, establishing a basis for product launch with selected partners and advancing other hypoallergens in the pipeline, including product candidates for grass pollen, dog, horse and peanut allergies.

Primary project objectives:

Demonstrating the safety and immunogenicity of rBet v 1 dm in a clinical setting
Aligning financial and business development strategies to support market access
Increase awareness of Desentum’s technology among the allergy community

Primary tasks for achieving the objectives:

Regulatory procedures	Preparation of a regulatory package for clinical trial authorization; discussion with regulatory authorities to ensure compliance
Phase I/IIa clinical trial	Testing the safety, tolerability and immunogenicity of Bet v 1 dm in a first-in-human clinical study
Business development	Building partnering relationships and market access strategy to ensure seamless late-phase clinical development and commercialisation
Communication	Communicating the project progress and results to educate the stakeholders and support the business development goals

AllergyVAX project started in Dec 2018 and ended in Jul 2021. Project duration was 32 months.

Project results

The First-in-Human clinical study in birch pollen allergic adults was completed in 2021. The results indicate a positive outcome of the study, although more data will be required for clinical proof-of-concept. It was concluded that the highest of the tested dosing regimens, a biweekly dosing regimen of DM-101 involving 5 ascending doses is safe and well-tolerated by subjects that suffer from seasonal symptoms of birch pollen allergy. Albeit the number of study participants was small, the immunological marker results indicated a favourable change in the markers associated with a protective response.

An unexpected result that derived from the project was new information regarding the impact of formulation on the potency of allergens. In parallel to the AllergyVAX project, formulation development work (not funded by the H2020 grant) has been conducted to exploit this information and produce an improved formulation of DM-101 for the next clinical study. The improved formulation has a potential to bring new properties to the product that can move it further beyond the state-of-the-art. Planning and preparations are ongoing for a next clinical study.

Even though the Covid-19 pandemic and pollen season caused delays, the AllergyVAX project enabled Desentum to successfully complete the First-in-Human clinical study, which is a key to reaching other milestones in the coming months and years. The goal is to set off a change in the way allergies are managed – from treating the symptoms to treating the disease.

Project news

25.10.2021 Desentum reports positive findings for the First-in-Human clinical study of lead product candidate in birch pollen allergic adults

11.5.2021 Dosing completed for Desentum’s First-in-Human clinical study of DM-101

30.11.2020 Clinical study with birch pollen hypoallergen DM-101 continues

26.3.2020 First-in-Human clinical study with DM-101 paused due to corona virus pandemic

15.1.2020 New scientific paper about hypoallergenic variants of horse allergen Equ c 1

1.11.2019 Desentum will run a clinical trial on its allergy vaccine this winter supported by 4 M€ of new investments

17.9.2019 Desentum aims to initiate clinical trials with its birch pollen allergy vaccine this fall

29.10.2018 Desentum wins a 1.9 M€ EU grant for first-in-human clinical trials

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 829933.

About Desentum

Desentum was founded by Finnish scientists with an ambition to stop the allergy epidemic by treating the cause of allergy - not just the symptoms.

How allergies work?

Allergies are caused by a fault in our immune system. Our body mistakes a harmless
substance, like pollen, as something harmful and attacks it.

GLOSSARY OF ALLERGY TERMS:

« Allergen

An antigen (i.e. allergen) that induces an allergic or hypersensitive response.
« Allergenic

A substance (such as a food or pollen), that has the capacity to induce allergy is defined as allergenic.
« Allergen immunotherapy

A process of administering allergenic extracts to patients who suffer from allergic rhinoconjunctivitis and allergic asthma to decrease the degree of hypersensitivity and symptoms by reducing immunologic responses to environmental allergens like pollen, dust, animal dander, and molds; also highly effective for preventing anaphylaxis in patients allergic to bee venom.
« Allergic asthma

An inflammatory disease of the lungs characterized by (in most cases) reversible airway obstruction. Originally, a term used to mean “difficult breathing”; now used to denote bronchial asthma.
« Allergic reaction

An adverse reaction involving the immune system, caused by inhaling, swallowing, or touching a substance to which a person is sensitive. It can also follow injections of medicines, insect stings, or insect bites.
« Allergic rhinitis

An allergic reaction affecting the lining of the nose and the eyes caused by inhaling airborne allergens such as dust mite, pollens or animal dander and also by eating certain foods. Symptoms may include itching, sneezing, blocked nose, runny nose, and itchy/watery eyes; may also occur concurrently with allergic conjunctivitis.
« Allergy

A chronic disease characterized by an overreaction of the immune system to protien substances - either inhaled, ingested, touched or injected - that normally do not cause an overreaction in non-allergic people. Hypersensitivity is typically caused by exposure to a particular antigen (allergen) resulting in a marked increase in reactivity to that antigen on subsequent exposure, sometimes resulting in harmful immunologic consequences. See also: allergic reaction.
« Anaphylaxis

The most severe type of allergic reaction involving many organs in the body. Onset of symptoms are immediate often affecting the breathing, and may be fatal if not treated immediately.
« Animal dander

Tiny scales from the skin, hair or feathers of an animal. Dander is a normal effluvium, but can induce an allergic reaction in people sensitized to it.
« Antibody

Antibody (also called immunoglobulin) is a molecule produced by B-lymphoid cells. It recognizes a unique molecule, which is called an antigen. Antibodies are present in the blood and body fluids. After binding an antigen, some antibodies can bind to surface receptors on immune cells, and in some cases they may neutralize pathogens. There are different classes of antibodies. The antibodies produced in an allergic reaction are of the IgE class.
« Antigen

An antigen is any substance that causes the immune system to produce antibodies against it. Antigens may be foreign substances from the environment, such as chemicals, bacteria, viruses, or pollen, or they may be formed inside the body, as with bacterial toxins or tissue cells.
« Antihistamines

Antihistamines are drugs commonly used for treating the symptoms of allergic reactions. They inhibit the action of histamine in the body by blocking the H1 histamine receptors in smooth muscles, vascular endothelial cells and central nervous system.
« Anti-inflammatory

Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation or swelling. About half of analgesics (painkillers) have anti-inflammatory properties.
« Atopic dermatitis

Atopic dermatitis (AD, a type of eczema) is an inflammatory, relapsing, non-contagious and pruritic (itchy) skin disorder. The cause of AD is unclear, but factors like genetics, dysfunction of the immune system, defective skin barrier and environmental exposures have been suggested. There is no cure to AD. Various treatments are used to manage the condition, the most common ones being moisturizers and topical corticosteroids.
« Atopy

Genetic tendency to develop certain allergies. Atopic individuals usually suffer from one or more of the following: eczema (atopic dermatitis), allergic rhinitis (hay fever), or allergic asthma. These maladies may also be accompanied by food allergies, allergic conjunctivitis and other allergic symptoms.
« Basophil

Basophils (basophil granulocytes) are a type of white blood cells that are involved in inflammatory reactions, particularly those related to allergies and asthma. When stimulated, basophils release histamine and other enzymes that can lead to inflammation, bronchoconstriction, and asthma symptoms. Basophils and mast cells are quite similar in appearance and function, but basophils are found in the blood, whereas mast cells reside in tissues.
« Beta blockers

Beta blockers are a class of drugs that target the beta receptors on the surface of cells that are part of the sympathetic nervous system (heart muscle, smooth muscles, airways, arteries, kidneys, etc.). Beta receptors lead to stress responses, especially when stimulated by epinephrine (adrenaline). Beta blockers interfere with the binding of epinephrine and other stress hormones to the receptor, and weaken the effects of stress hormones.
« Conjunctivitis

Conjunctivitis (aka pink eye) is an inflammation of the conjunctiva. The conjunctiva lines the inside of the eyelids and covers the white part of the eye (sclera). Conjunctivitis can be due to a viral or bacterial infection or an allergic reaction. Redness and swelling of the conjunctiva, as well as watering and itching of the eye are typical symptoms of all types of conjunctivitis. Bacterial conjunctivitis also involves mucopurulent discharge.
« Dermatitis

Dermatitis, or eczema, is a general term describing a non-contagious inflammation of the skin. It can be due to an inherent skin defect, direct contact with an irritating substance, or an allergic reaction. Symptoms of dermatitis can include redness, dryness, itching, swelling, crusting, flaking and even cracking of the skin, which can cause oozing and bleeding.
« Desensitization

The reduction or abolition of allergic sensitivity or reactions to the specific antigen (allergen). In allergen immunotherapy, desensitization is accomplished by administrating increasing doses of the antigen, starting from very small doses that induce little or no symptoms, and increasing the dose over time until the immune system develops a tolerance to the substance.
« Drug Allergy

Sensitivity (hypersensitivity) to a drug or other chemical. Allergic symptoms may occur regardless of the form the drug is taken in (pill, injection, liquid), and vary in severity: itching, swelling, rash, wheezing, abdominal pain, vomiting or even anaphylaxis. The most common drug allergy is penicillin.
« Dust Mite

House dust mites are small mites invisible to the naked eye. They feed on organic matter shed by humans, such as flakes of skin, and need at least 50% humidity to survive. House dust mites thrive in the stable environment provided by houses, and are widely distributed in homes. House dust mite is a common cause of asthma & allergic rhinitis.
« Eczema

Generic term for inflammatory conditions of the skin. Eczema is characterized by one or more of the following symptoms: redness, swelling, itching and burning, crusting, flaking, blistering, cracking, oozing and bleeding. In a later stage lichenification and scaling can follow. Eczema is often hereditary and associated with allergic rhinitis and asthma.
« Eosinophils

Eosinophils are a type of white blood cells whose natural role is to defend the body against parasites. The number of eosinophils in the blood increases during parasite infections, but also during allergic reactions. At the site of the allergic reaction eosinophils release chemicals that cause damage to the surrounding tissues.
« Food allergy

An adverse IgE-mediated immune response to specific foods such as peanuts, tree nuts, shellfish, egg, and milk. There are also non-allergic food hypersensitivities that can be caused by a lack of digestive enzymes, inability to absorb certain nutrients or non-IgE-mediated immune responses, for example. These should not be confused with a true food allergy.
« Hay fever

Hay fever (allergic rhinitis) is an acute irritative inflammation of the mucous membranes of the eyes and upper respiratory passages induced by seasonal allergens such as pollen from trees, grasses, weeds or flowers. The inflammation is accompanied by itching and profuse, watery nasal secretion. Despite the name, hay fever usually doesn’t involve temperature elevation. Hay fever episodes recur annually approximately at the same time of the year, depending on the flowering season of the inducing plant.
« Histamine

A vasodepressor amine found in all body tissues. Histamine causes capillary dilation, contraction of smooth muscle cells, stimulation of gastric acid secretion and acceleration of the heart rate. It is involved in local immune responses, but also has gastrointestinal regulatory functions and acts as a neurotransmitter. In the immediate hypersensitivity reaction (allergic reaction) histamine is released by mast cells and basophils. It is responsible for the symptoms of allergic rhinitis.
« Hives

Urticaria is commonly referred to as hives. It looks like nettle rash, and consists of itchy, raised lumps surrounded by red area. Hives are often caused by an allergic reaction, but other causes are also possible.
« Immunoglobulins

Immunoglobulins, also known as antibodies, are proteins found in blood and in tissue fluids. Immunoglobulins are produced by cells of the immune system called B-lymphocytes. Their function is to bind to substances in the body that are recognized as foreign antigens (often proteins on the surface of bacteria and viruses). This binding is a crucial event in the destruction of the microorganisms that bear the antigens. Immunoglobulins also play a central role in allergies when they bind to antigens that are not necessarily a threat to health and provoke an inflammatory reaction.
« IgE

Immunoglobulin E, a class of antibody associated with the allergic response. IgE normally plays a role in defending the body against parasites, but in an allergic response it triggers the release of histamine from the mast cells by binding to the high-affinity FcεRI receptors on the mast cell surface.
« IgG

Immunoglobulin G, the most common immunoglobulin (antibody) in blood circulation and extracellular fluid. IgG protects the body from various types of infections. It can bind viruses, bacteria, fungi and toxins, and neutralize them by immobilizing them, tagging them for phagocytic cells or activating the complement system, a part of the innate immune system that helps in clearing pathogens. Allergen immunotherapy aims to reduce the IgE-mediated response to allergens, allowing the IgG-mediated response to neutralize the allergens.
« Immune system

An intricate complex of interrelated cellular, molecular, and genetic components that provides a defense, the immune response, against foreign organisms or substances and aberrant native cells.
« Immunotherapy

Treating a disease by inducing, enhancing or suppressing the immune response. Originally, immunotherapy was therapeutic administration of serum or immune globulin containing preformed antibodies produced by another individual. Currently, immunotherapy includes nonspecific systemic stimulation, adjuvant, active specific immunotherapy, and adoptive immunotherapy. New forms of immunotherapy include the use of monoclonal antibodies. Activation immunotherapy stimulates the immune system, and is used in cancer treatment, for example, to destroy tumors. Suppression immunotherapy, by contrast, dampens the immune response and is used for treating autoimmune diseases and preventing the rejection of transplanted organs. Allergen immunotherapy is also suppression immunotherapy as it decreases the hypersensitivity reaction of the immune system.
« Latex

Natural latex is an emulsion or suspension produced by some seed plants. Latex contains suspended microscopic globules of natural rubber. There are similar synthetic materials as well: polystyrene, polyvinyl chloride, etc. The word latex is also used for natural latex rubber, which is used in latex gloves, condoms, etc. Many people are allergic to rubber latex.
« Lymphocyte

Lymphocytes are white blood cells that can be found throughout the body in lymphatic tissue. They are divided in two main groups, B cells and T cells. When activated by antigens, B cells can differentiate into antibody-secreting plasma cells, whereas T cells can divide rapidly and produce new T cells sensitized to the antigen. Lymphocytes are an essential part of the adaptive immune system, which mounts a tailor-made defense when dangerous invading organisms penetrate the body's general defenses.
« Mast cell

Mast cells are leukocytes that are found in tissues throughout the body, particularly in tissues where they can participate in recognizing foreign substances. Typical examples of such tissues are skin, airways and the intestinal tract. Mast cells are involved in the immediate hypersensitivity reaction by releasing histamines, leukotrienes and other chemical mediators.
« Mold

A filamentous fungus, generally appearing as a circular colony that may be cottony, wooly, or glabrous, but with filaments that are not organized into large fruiting bodies, such as mushrooms. Molds release spores that spread through the air. These spores are the cause of symptoms in people allergic to mold.
« Pollen

Pollen consists of microspores of seed plants carried by wind or insects before fertilization. Pollen allergy is a major cause of allergic rhinitis. Many wind-pollinated grasses, trees and weeds produce a large amount of light-weight pollen that induces allergic symptoms in sensitized individuals. The prevalence of specific pollen allergies varies greatly depending on the geographic location.
« Respiratory Allergies

Allergy caused by inhaled substances such as pollen, hours dust mite, moulds and pet dander. Respiratory allergy usually doesn’t cause severe, anaphylactic reactions, but the symptoms can still have a significant impact on the quality of life. The irritation of airways, eyes and skin can lead to allergic rhinitis, asthma, eczema and urticaria.
« Rhinitis

Irritation and inflammation of the mucous membrane inside the nose, often due to an allergy to pollen, dust or other airborne substances. Seasonal allergic rhinitis also is known as "hay fever," a disorder which causes sneezing, itching, a runny nose and nasal congestion.
« Sinusitis

Inflammation of the mucous membrane of any sinus, especially the paranasal. See also: rhinosinusitis
« Skin Prick Test

A test to identify reactions to allergens. A common method to perform skin prick test is to apply separate droplets of allergens on the skin and prick the skin under each droplet with a tiny lancet that only penetrates the surface of the skin. This will carry the allergen into the skin. A positive test result is a reaction where a raised itchy lump (wheal) develops within 15-20 minutes.
« Urticaria

An eruption of swollen, itching wheals, colloquially called hives. Acute urticaria, lasting less than 6-8 weeks, is often due to a state of hypersensitivity to foods or drugs, but can also be triggered by infection, for example. Chronic urticaria can be due to many things, and often the cause will remain unclear. In addition to the hypersensitivity and infection, possible underlying causes are physical agents (heat, cold, light, friction), autoimmune reactions or psychic stimuli.