Community Research and Development Information Service - CORDIS

H2020

ATx201 Report Summary

Project ID: 736508

Periodic Reporting for period 1 - ATx201 (A novel class of antibiotics for treatment of infected atopic dermatitis: an innovative solution for a significant unmet medical need)

Reporting period: 2016-08-01 to 2016-11-30

Summary of the context and overall objectives of the project

AntibioTx`s innovation project to cure infected AD will bring several societal benefits within the European boundaries and beyond, mostly related to the Health dimension. As well as being a value in itself, health is a precondition for economic prosperity and efficient spending on health can promote growth and welfare. AD is the leading health burden of skin diseases and is associated with significant co-morbidity . AD affects more than 30 million patients in Europe, and 60 million patients in the EU, US and Japan combined, with increases in Western European prevalence rates as the main driver of growth during the last decade . Moderate-to-severe forms of AD have a substantial impact on the quality of life of patients and their relatives, carrying a significant socioeconomic burden. Comorbidities include sleep deprivation, psychological distress (including increased suicide rates), asthma and various allergies . Population studies of Health-Related Quality of Life (HRQoL) scores consistently find that AD is among the most severe diseases of children with greater negative impact on well-being than epilepsy, diabetes, asthma and even cystic fibrosis . The negative impact extends to the families of children with moderate or severe disease, who suffer more from the disease compared to families with diabetic children . Furthermore, over 90% of AD patients are colonized and frequently infected by Staphylococcus aureus . Colonization and infections by S. aureus are directly linked to the flare-ups and increased severity of AD. However, there are currently no treatments with regulatory approval for such infections. Rampant off-label use of antibiotics has led to significant antibiotic resistance and stewardship problems. In the EU, 25.000 people die each year from an infection due to antibiotic-resistant bacteria. Infections due to these selected multidrug-resistant bacteria in the EU result in extra healthcare costs and productivity losses of at least €1.5 billion each year . If the current trend is not altered, 300 million people worldwide are expected to die prematurely because of drug resistance over the next 35 years.

ATx201 is an excellent solution: it has been proven to act as a potent antimicrobial while not inducing resistance in bacteria and providing the European dermatology industry with unparalleled efficacy in the eradication of the bacterial infections. The novel mechanism of action underlying the outstanding properties of ATx201 supports repeated use of the product and extends the functional life of ATx201 while delivering effective cures to patients and decreasing unnecessary costs in the European healthcare sector. In this framework the ATx201 project is directly providing a sounding solution for the European Health Challenges: 1) improve our ability to monitor health and to prevent, detect, treat and manage disease; 2) and test and demonstrate new models and tools for health and care delivery.

ATx201's overall ojectives are listed below:
1) Human proof-of-concept
2) Phase III clinical trial ready
3) ATx201 confirmed as preferred treatment for infected AD
4) Develop a comprehensive Marketing and Communication Strategy
5) Maintain a sound IP management and scale-up strategy with manufacturing partners engaged for Union-wide and global distribution

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

AntibioTx’s ambition is for the ATx201 drug to be adopted throughout Europe and US as a next generation of topical antibacterials and the first approved product for treatment of infected AD. To achieve this goal, AntibioTx needs to carry out a successful clinical development plan, with approximately 540 patients at dermatologic clinics within the EU and US. These studies will validate the Target Product Profile (TPP) and will make ATx201 an attractive asset for dermatology players. Once successful accomplished the human proof of concept in Phase II trial, ATx201 will be a uniquely differentiated project requiring only one pivotal Phase III study for the marketing approval (Fig.2).
Rationale: ATx201 can be used to treat and prevent a number of infections such as infected AD, impetigo, pre-surgical decolonization and diabetic wound infections, but in a risk-adjusted evaluation it has been concluded that infected AD is the optimal first target indication for four primary reasons: A) No effective treatments available, B) Strong match between indication and ATx201 TPP, C) High likelihood of achieving clinical success, and finally D) Large market opportunity with attractive pricing.
ATx201’s Current Stage: The current stage of development of the proposed ATx201 antimicrobial solution aligns with a Technology Readiness Level 7 since the drug compound is ready to be tested in an operational environment represented by 40 patients suffering from infected AD. The compound has already been tested in clinical studies and the risk is therefore significantly reduced, since: 1) Systemic concentrations following application of ATx201 are approx. 1,000-fold below proven tolerated levels; 2) Local tolerability on the skin proven in clinical studies >250 people applying the API daily for up to 6 months with no reporting of adverse events; 3) Clinical effect against S. aureus (incl. MRSA) and qualified by in vitro and in vivo effect data and pharmacokinetics (PK) measures in human skin as well as from minipigs. As a result it is expected that ATx201’s antibiotic effect will translate better than most pharmaceuticals from pre-clinical to clinical studies. As of Q4 2016, ATx201 is undergoing Phase I study (multiple formulations) at Medical University of Vienna assessing the safety and low systemic exposure in healthy skin. Importantly, the Phase II study is already planned and approved by the Austrian regulatory authorities. Thus, Phase II/III trials specifically on infected AD patient population, will provide the validation required to achieve all the relevant prerequisites to take the ATx201 drug to the market (MAA – Marketing Authorization Application). Together, Phase II and III clinical trials, would elevate ATx201 to a Technological Readiness Level of 9, primed for successful commercialization and penetration into the infected AD go-to market.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

"Required developments: In Q1 2017, AntibioTx successfully completed subject enrolment of an elaborated Phase I study enrolling 36 healthy individuals, which has been setup in accordance with EMA and FDA standards at the Medical University of Vienna under the supervision of Dr. Markus Zeitlinger and Dr. Georg Stingl who are world recognized authorities within infectious disease and AD, respectively. The objective of this study is to assess the local and systemic safety of ATx201 in healthy volunteers before proceeding with clinical trials in AD patients. AntibioTx has selected three different topic formulations with niclosamide as API (active pharmaceutical ingredient). Therefore, in Phase I of the study, all three formulations have been applied to healthy volunteers to determine the best formulation to proceed to Phase II. As reflected in the minutes from the Scientific Advice meeting with the Austrian Regulatory Authorities’ ATx201 can progress from Phase I to Phase II without further approval from the regulatory authorities provided that there are no significant adverse events observed in the Phase I study. Based on preclinical studies, third-party clinical data, and data from the first healthy volunteers treated with ATx201, AntibioTx is preparing for Phase II. As outlined above, Phase I clinical milestone (M8) has come along with accomplished medical writing and GMP manufacturing/stability tests of the trial product for Phase II (M7). The rationale of the product development plan is now focussed on addressing the main objectives essential to prove the commercial viability of ATx201: 1) Achieve human proof of concept (PoC) and identify the optimal dosing of the drug to be administrated (Phase II) and 2) Clinically validate ATx201 as a preferred treatment for infected AD, 3) Establish the Tx-class as a new class of antibiotics with a novel mode of action
During the feasibility period AntibioTx has successfully defined the most suitable conditions for this product roadmap (i.e. Phase II clinical trials) to be performed. During the clinical validation plan, AntibioTx will work closely with Contract Research Organisations (CROs) to assure regulatory compliance, obtain clinical trial (Phase III) authorisation and prepare the appropriate documentation for the trial implementation; AntibioTx will also utilise the service of Contract Manufacturing Organisations (CMOs) for drug Chemistry, Manufacturing, and Controls (CMC) in order to produce GMP-batches to be used for the last pivotal clinical trial.

Value Proposition: AntibioTx solves the main issues limiting effective treatment of infected AD, including efficacy against antibiotic resistance bacteria, duration of treatment, safety and sustainability bringing benefits to the the entire healthcare system:
Value#1: Value for Patients (end-users): ATx201 offers 1) better treatment due to effect against resistant bacteria; 2) repetitive and long term effective treatment of infected atopic dermatitis due to significantly reduced resistance mutation frequency; 3) reduced need for oral treatment and systemic exposure and toxicity.
Value#2: Value for physicians/dermatologists (customers): ATx201 offers 1) Effective treatment and decolonization of Gram-positive bacteria over extended periods (increased physicians’ referral based on increased patients’ satisfaction); 2) Better patient compliance due to reduced need for multiple treatments; 3) Lower risk in contributing to the rise and spread of antibiotic resistance.
Value#3: Value for the distributors (clients): The clients of AntibioTx distributing ATx201 benefit from selling a highly differentiated product, which is first in class and first drug approved for infected AD. Given the substantial unmet medical need these properties will translate into a higher market share and additional revenues for the clients. Given the fact that ATx201 is based on an easy to synthesize chemical scaffold and AntibioTx has already established scalable GMP manufacturing process for the final product, clients benefit from a fast and lean manufacturing process.
Value#4: Value for the healthcare/society economy: ATx201 offers 1) Lower cost of treatment due to fewer physician visits; 2) lower cost due to reduced likelihood of oral treatment and hospitalization; 3) lower cost to society due to increased patient wellbeing and fewer patient sick days.
Value#5: Value for the society: ATx201 belongs to a new chemical class of antibiotics with a novel powerful mode of action which overcomes both de novo and existing multidrug resistance. ATx201 has therefore a strong potential to fundamentally change the treatment paradigm of dermatological infections by providing an effective, once-daily, short duration, non-systemic treatment for a significant unmet medical need. Furthermore, ATx201 has a short path to the market and high probability of success which will validate the Tx-class for antibacterial purposes as well as the company. This will reduce societal resources spent to address the health and economic burden of AMR."

Related information

Record Number: 198211 / Last updated on: 2017-05-17
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