“We want to unlock the therapeutic potential of AAT for patients with inflammatory lung diseases”

The start-up AATec Medical is developing a multi-product platform based on recombinant alpha‑1 antitrypsin (AAT) for patients with inflammatory respiratory diseases. Their lead candidate, ATL‑105, has already demonstrated its special mode of action in a number of preclinical studies and is to be clinically tested in a proof-of-concept study in patients with non‑CF bronchiectasis (NCFB). We talked to CEO and co-founder Dr Rüdiger Jankowsky about a dynamic first year, their next fundraising round, and the importance of clearly defining oneself.

Dr Jankowsky, AATec Medical recently celebrated its first birthday. How would you describe the past year?
It has been a very eventful year. Since the birth of AATec, which meant the closing of our first financing round and the technical start of our activities, we have achieved a lot. We have made significant progress on the product development side, both in terms of the technological platform and in the preclinical testing of our active ingredient in various diseases. We have also taken an important step in solidifying our clinical study programme and have decided on non-cystic fibrosis bronchiectasis (NCFB) as the first indication – an indication with an enormous medical need. This year, we have been able to bring several experts into our Scientific Advisory Board, who are helping us, among other things, to develop our clinical strategy.

We see ourselves as a project management organisation with the corresponding IP and work exclusively with partners selected according to our criteria, who support development with their expertise. To this end, we have built a lean team that manages our development activities. In this respect, it has been a dynamic year, twelve months of constant activity.

You mentioned the product platform. How does your approach work and what makes it special?
Our product approach is based on a new recombinant form of a human protein. This is alpha‑1 antitrypsin (AAT), a protein found in significant quantities in the blood. AAT is a serine protease inhibitor with anti-inflammatory and anti-infective properties. Our approach is to deliver recombinant alpha‑1 antitrypsin to the lungs of patients. In many chronic inflammatory lung diseases, as well as in acute lung diseases, there is an imbalance between proteases and anti-proteases. We know that by targeting alpha‑1 antitrypsin, we can reduce this imbalance, and thus address these diseases. This makes AAT very interesting as a platform, because the disturbed balance between proteases and anti-proteases occurs in several respiratory diseases: in COPD, in a large subgroup of asthma, in acute lung injury, in infectious diseases, and also in our first target indication, non‑CF bronchiectasis. We believe that our therapeutic protein can be used to address a wide range of diseases, and that it will enable us to effectively treat chronic and acute lung diseases in the future.

How is your protein administered, and what advantages does it have over other forms of administration?
We administer our active ingredient through inhalation. Together with our partner Beurer, we have developed a nebuliser that allows the protein to be nebulised and delivered directly into the lungs – to the site of inflammation – by inhalation. This is expected to result in a faster onset of action than with systemic administration – for example, via a tablet.

The second point is the dose. With inhalation, it is possible to achieve a high concentration of active ingredient in the lungs with a low total dose. This is different from systemic administration, where higher doses are required because the active ingredient first travels through the blood to the site of action.

In this respect, administration by inhalation offers a combination of rapid onset of action, and a low total dose. We are currently estimating one inhalation session per day, lasting a maximum of 15 minutes. This is very convenient for patients.

Where do you stand with your lead programme ATL‑105?
We have already been able to demonstrate the preclinical feasibility with our active ingredient. We have conducted a large number of target engagement studies, which have shown that our compound can effectively inhibit its targets. We have been able to demonstrate this at the cellular level in a variety of studies, and are currently in the process of verifying the results in an additional confirmatory preclinical experiment. This will enable us to demonstrate that our mechanism of action works. The following step is a preclinical study on safety and tolerability. We expect to be able to start this in the first half of 2025.

Why did you choose non-CF bronchiectasis (NCFB) as the lead indication?
Non-CF stands for non-cystic fibrosis, so we are setting ourselves apart from cystic fibrosis. According to current estimates, there are more than 2 million patients in western countries with our main indication. We assume that there are significantly more patients in China. NCFB is currently a severely underdiagnosed disease, but it is already one of the most prevalent chronic lung diseases, after COPD and asthma. There are no specifically approved therapies for the patients affected.

Due to the mode of action of our compound, we have an excellent starting point for addressing this disease therapeutically. NCFB is an inflammatory disease of the respiratory tract that is essentially driven by proteases, which overshoot in their activity and cause chronic inflammation. These can be regulated by alpha-1 antitrypsin. In addition, we know that we can reach the crucial areas of the lung directly through inhalation with our active ingredient. This is a strong therapeutic rationale that we have developed together with leading international clinical experts.

What is the competition like in this indication?
There is a very interesting development dynamic in this area. The initial approach is currently focused on the inhibition of DPP‑1. These active ingredients also interfere with the protease‑antiprotein imbalance but influence the activity of proteases at an earlier stage during the maturation of neutrophils. Promising clinical data for this therapeutic concept were published in NCFB this year. This is an important milestone for patients and doctors, because it means that the disease can be treated at its root for the first time. However, these drugs have a limited therapeutic effect, which is insufficient to offer patients a rapid and long‑term effect. This is precisely where we have an advantage with our mechanism of action. Firstly, we are active across a broad spectrum because we have anti-inflammatory effects, anti-proteolytic effects, and we also have anti-infective activity. We believe that this multimodal approach allows us to achieve a better therapeutic effect than DPP‑1 inhibitors.

Our second advantage is the time of onset of action. This is delayed in DPP‑1 inhibitors due to the principle of action; the therapeutic effects only occur after a few months. With inhalation administration, we go directly to the lungs and assume that this can lead to a rapid onset of action. We would like to transfer these advantages into a clinical benefit.

You have already mentioned the clinical experts. What role does the Scientific Advisory Board play for AATec?
The clinical experts are very important for our product development. We are a focused, product-oriented company and want to get our product to the patient as quickly as possible. To this end, it is necessary to clearly define the medical need: this is expressed in symptoms and, very specifically, in the patients’ quality of life. We know that we can only develop an effective therapy if we design the clinical studies correctly. That is why it is so important for us to have highly experienced and internationally renowned specialists on board to support us in designing our clinical studies. Our scientific advisory board includes leading experts in the fields of bronchiectasis, COPD, aerosols and infectious diseases. This clinical know-how gives us a significant advantage in designing our clinical development program.

What makes respiratory diseases such an important area in your view?
Due to the pandemic, this therapeutic area has a certain history. However, the pandemic has partly distracted from the topic of chronic inflammatory lung diseases because there was a focus on respiratory viral diseases. Unfortunately, this has pushed into the background the fact that there are a large number of patients worldwide suffering from chronic inflammatory lung diseases. When I think of COPD and asthma, I think of hundreds of millions of patients, and there are many millions with bronchiectasis and other diseases. These needs are not being met by current therapeutic options, which means that these patients are effectively underserved. Not being able to breathe freely not only reduces a patient’s quality of life but can also lead to life-threatening situations – which kill millions of people a year. We would like to address this, although we are aware that we are entering an area that is not being addressed by many companies. However, we believe that there is a moral obligation to provide medication for these patients. This is our commitment.

How is AATec currently financed and what are the next steps in this regard?
We completed our seed financing in 2023 with a total of approximately €2.7 million. This allows us to finalise the preclinical development of our product candidate. We are currently in the process of fundraising for the start of clinical trials and are in discussions with a number of investors. We have already received significant interest, which is certainly due to the clear product focus of our company. We intend to close this financing round in the next few months, which will raise a total of approximately €15 million for the first clinical trial and related preparations, and then start preparations for the clinical trial.

AATec has just moved into the IZB. What do you expect from this new location?
We know that the IZB is an excellent location for companies at our stage and in our industry. The IZB offers excellent conditions for start-ups. On the one hand, it offers favourable conditions and, on the other, an excellent environment with many other companies. This provides the appropriate network. We also know the many supporting programs offered by the IZB – including the many events – actively contribute to our search for partners and other activities needed in our industry.

From your many years of experience as CEO of various life science start-ups, what advice would you give to young founders?
I think the most important aspect for a young company is to define itself as early and as seriously as possible. By that I mean defining its goals, positioning itself clearly in the market, including in relation to the competition, and – if possible – defining its products. I recommend that every start-up does this as soon as possible. This allows for a clear focus within the company and creates recognition outside the company. Although many companies are technology-driven, I believe that products and target markets should be defined as early as possible, depending on the business concept. I can speak from a pharmaceutical development perspective and reflect what I see in the market: as a start-up, you should be recognisable as early and as clearly as possible. And recognisable means: why are you doing this? What are you doing? Is there a demand? This demand is later translated into commercial potential.