Technology

Allergies are often managed by avoiding the allergen or by using medication to relieve symptoms. However, avoidance is not always possible, and medication may not offer sufficient symptom control. Allergen immunotherapy (AIT) is the only available treatment that affects the underlying condition by increasing tolerance to the allergen, but the treatment typically takes years, has unpredictable efficacy, and can involve a risk of severe allergic reactions during treatment.

Safe and successful allergen immunotherapy with recombinant hypoallergens

Desentum ’s hypoallergens are designed to induce a protective immunological response without compromising safety during treatment:

Targeted modifications in the allergen protein to reduce IgE cross-linking, thus reducing allergenic potential during immunotherapy
Native conformation of the hypoallergen retained to ensure that the protective immunological response induced by the hypoallergen also works against natural allergens
Novel formulation for controlled release of the active substance after injection, further increasing safety
Recombinant production for consistent, high-quality manufacturing of hypoallergens

The goal is safe and effective subcutaneous allergen immunotherapy with significantly lower number of injections compared to standard subcutaneous AIT.

How allergy and immunotherapy work

Allergies are caused by an overreaction of our immune system. A normally harmless substance – like pollen, food, or cat saliva – will cause the immune system to defend the body against it.

How allergy and immunotherapy work

Allergies are caused by an overreaction of our immune system. A normally harmless substance – like pollen, food, or cat saliva – will cause the immune system to defend the body against it. Type 1 hypersensitivity, mediated by immunoglobulin E antibody (IgE), causes allergic reactions such as sneezing, itchy eyes, running nose, rash, abdominal pain, or vomiting. The most severe allergic reaction, anaphylaxis, can rapidly develop into a life-threatening condition.

Difference between healthy response and allergy

When the immune system encounters an allergen, antigen-presenting cells (APC) introduce the allergen to naïve T helper cells (Th0).

In a healthy individual, the Th0 cells differentiate into T helper type 1 cells (Th1). Th1 cells activate B cells that differentiate into plasma cells and produce allergen-specific immunoglobulin G antibodies (IgG). The IgG antibodies have a protective function. They help to immobilize and destroy the allergens without causing an allergic response.

In some people with atopic predisposition, natural allergen exposure can lead to sensitization and allergy. Instead of Th1, the naïve Th0 cells differentiate into T helper type 2 cells (Th2). This path leads to B cells differentiating into plasma cells that produce allergen-specific immunoglobulin E antibodies (IgE). IgE antibodies bind to the surface of mast cells. On subsequent allergen exposure, the allergen cross-links them, and the mast cells release histamine and other cytokines that cause the allergic symptoms.

Allergen immunotherapy (AIT)

The goal of allergen immunotherapy is to re-educate the immune system, thus directing it towards the healthy Th1 response. For many allergies (pollen, house dust mite, animals, bee venom, etc.), AIT has been available for a long time. Traditional allergen immunotherapy is a method where gradually increasing doses of the natural allergen are administered by subcutaneous injections. Alternatively, daily sublingual drops or tablets can be used for some allergies. This desensitizes the body and tweaks the immune response away from the allergic mechanism, towards a healthy response. The treatment is usually continued for 3–5 years, depending on the allergen and the desired outcome.

Immunotherapy increases tolerance to the specific allergen and reduces the need for medication. The effect is sustained even after the treatment period is over. However, traditional allergen immunotherapy with natural allergens takes a long time and the up-dosing requires careful medical supervision to minimize the risk of a serious allergic reaction (anaphylaxis).

For food allergies, availability of immunotherapy is very limited, and the treatment effect is not sustained if the treatment is stopped. The standard of care for most food allergies is allergen avoidance and carrying an epinephrine autoinjector in case of accidental exposure.

Cells and antibodies - Th1-Th2 route - for web EN

Wild-type allergen

Modified allergen

IgE antibody

IgG antibody

If you are allergic, your body produces allergen-specific immunoglobulin E (IgE) antibodies. The allergens cross-link the IgE antibodies on the surface of mast cells. This triggers the allergic symptoms.

The modifications in our hypoallergens are designed to prevent IgE cross-linking. This reduces the risk of an allergic reaction during immunotherapy. Instead, the hypoallergens induce the production of protective immunoglobulin G (IgG) antibodies.

Next time you encounter natural allergens, your body uses the IgG antibodies to recognize and destroy them instead of launching an allergic reaction. This behavior stays in the immunological memory, protecting from allergy in the future.

The technologies we use allow us to precisely characterize hypoallergen structure and interaction, design targeted modifications to them and evaluate potential product candidates.

Mass spectrometry

Native mass spectrometry is an emerging technology that allows the topological investigation of protein complexes with high sensitivity. This unique tool provides us complementary information to established technologies in structural biology. It also provides additional information on exact protein complex-compositions, structures and dynamics. This technology is extremely useful for determining the correct folding and structure of hypoallergen candidates. It also provides useful information on allergen-IgE antibody complexes.

Protein crystallography

Crystallisation of proteins and protein complexes is one way to study the structure of proteins. Protein crystals are exposed to X-rays in unique synchrotrons and the diffraction spectrum received in this kind of analysis provides us valuable information about the primary, secondary, tertiary and even quaternary structures of proteins under investigation. This method gives us a very precise way to design changes in allergen molecules in order to achieve the hypoallergenic properties we aim at.

HRA histamine release assay

The biological activity of the hypoallergen candidates can be analysed in a so called histamine release assay. In this assay stripped basophil cells are challenged with allergen and hypoallergen molecules and the subsequent release of histamine is measured. The amount of histamine released by a hypoallergenic product candidate opposed to a wild type allergen tells us if the hypoallergen has a potential to be used as an immunotherapeutic product.

Scientific articles

Haka J et al. 2019. Development of hypoallergenic variants of the major horse allergen Equ c 1 for immunotherapy by rational structure based engineering. Sci. Rep. 9(1):20148

Niemi MH et al. 2015. Dimerization of lipocalin allergens. Sci. Rep. 5, 13841; doi: 10.1038/srep13841

Rouvinen J et al. 2010. Transient dimers of allergens. PLoS One. 5(2):e9037

Niemi M et al. 2008. Characterization and crystallization of a recombinant IgE Fab fragment in complex with the bovine beta-lactoglobulin allergen. Acta Crystallogr Sect F Struct Biol Cryst Commun. 64(Pt 1):25-28.

Niemi M et al. 2007. Molecular interactions between a recombinant IgE antibody and the beta-lactoglobulin allergen. Structure 15(11):1413-21.

Product pipeline

We have completed a First-in-Human clinical study with the lead product candidate, birch pollen hypoallergen DM-101. Further clinical development of DM-101 is ongoing. Each allergy requires its own hypoallergen, so other hypoallergens are in development. The product line will be expanded as we manufacture new modified hypoallergens.

Birch pollen

First-in-Human clinical study completed
Novel formulation developed
Second clinical study ongoing

Phase 1

Peanut

Modified Ara h 2 hypoallergen candidates produced
Preclinical evaluation ongoing
Clinical phase targeted in 2025-2026

Preclinical

Grass pollen

Modified Phl p 1 hypoallergens produced and evaluated
Drug candidate selection ongoing

Preclinical

Clinical trials

DM-101-C-001

The randomised, double-blinded, placebo-controlled, dose escalation study was designed to evaluate the safety and tolerability of subcutaneous immunotherapy with DM-101 in birch pollen allergic adults. Immunological markers such as allergen-specific IgE and IgG were also analysed.

DM-101 was found to be safe and well tolerated in a dose regimen of 5 ascending doses, and immunological marker results indicated a favourable immunological response.

DM-101-C-002

The ongoing trial is a randomised, double-blind, placebo-controlled DM-101PX dose escalation trial to investigate the safety, tolerability, and exploratory efficacy (following environmental allergen exposure in a chamber) of DM-101 in participants with birch pollen allergy.

DM-101PX is a formulation of DM-101 optimised to support controlled release of the active substance after subcutaneous injection.