The journey of a new inhaler from a simple concept to market availability is a long, complex, and multi-stage process. However, these stages are necessary to ensure the safety of ‘PRESS’—our novel therapeutic approach, which will be of great benefit to asthmatic patients. Each milestone is important for us to plan preclinical validation, clinical trials, regulatory approval, and eventually its implementation in the market. Our production development roadmap is generally applicable, and to reach our goal, we’ve made sure we are following all the typical phases through the scope of lab safety guidelines.
We began preparing for our project this year by putting concrete concepts for our new therapeutic approach, so we can imagine the delivery mechanism of the active ingredient of the drug that targets the production of TSLP and induces the symptoms of asthma. We conceptualized how engineered Lactobacillus bacteria can produce a reduction of the pathogenesis of the asthma inflammatory mediator (TSLP), including finding a synthetic gene circuit that will be delivered to the respiratory cells.
The dynamics of our idea this year is an inhaler that targets asthma through genetically modified Lactobacillus bacteria. The bacteria are genetically modified through their siRNA, which targets mRNA for knocking down TSLP production through inducing the dicer enzyme, which decreases the level of translation and the inflammatory mediator, which therefore decreases asthma pathogenesis.
The pre-clinical development involves data about the safety and biological efficacy of our inhaler before testing it on humans.
Divided into two main stages: In-Vitro study and In-Vivo study.
In our approach, we needed to validate multiple sectors, including the conditioned expression of siRNA, then siRNA loading into the membrane vesicles of Lactobacillus plantarum, the endosomal escape via the mutated version of LLO, and lastly the knockdown of TSLP level via siRNA. Additionally, by getting access to BSL-2 labs, which are essential for handling our modified Lactobacillus plantarum strain, we will be able to validate the mechanism of action and stability of Lactobacillus.
Selecting the appropriate animal will make it easy for us to follow the distribution of Lactobacillus and enable us to study inflammatory mechanisms efficiently. After searching for the best animal fit for our use, we found out that the most common animals studied in the last two decades are mice, since they have successfully reproduced many features of asthma, such as high levels of serum. Specifically, immunoglobulin E (IgE) and airway inflammatory markers.
The process will benefit us for validation of our hypotheses and help us assess multiple aspects like the delivery, stability, and distribution of our altered bacteria, which will be taken through inhalation and to the respiratory system of modified Lactobacillus via DPI.
These assessments are essential before the implementation of our inhaler since they will allow us to identify the best design for the inhaler and provide an estimation of our drug's efficacy, the best time of application, and the route of administration. Finally, it would be useful for us to detect the dose range.
Throughout every step of building our PRESS treatment, we made sure safety came first; it was not something we added later, but something we built in from the very beginning. Our team created five different safety systems that work together, including our kill switches that stop bacteria if they escape, sensors that detect dangerous conditions, and our special olive-based system that was designed to destroy any escaped bacteria from culture media in just 30 seconds. From how we train people in our lab to following all the rules and regulations, we built protection for everyone: patients, doctors, lab workers, and the environment. Our safety approach works much better than the standard requirements, giving us strong protection and evaluating the efficacy of our treatment. We worked closely with six safety experts and filled out all the required forms for our special components.
It's our duty to ensure that everything we do keeps patients, medical staff, lab personnel, and the general public safe. Our Safety page has all the information you need to understand our safety procedures.
The biodistribution phase helps us understand where our modified Lactobacillus moves in the body, how long the bacteria survive, and when they are naturally eliminated from the system. This is critical to the safety of our designed probiotic therapy. Hence, Dr. Ahmed Mansour assisted us in understanding the biodistribution patterns of our bacteria within the respiratory tract.
On the other hand, the mechanism of action of our bacterial therapy focused mainly on how our engineered Lactobacillus will impact the asthmatic patient's lung and provide therapeutic benefits through targeted TSLP silencing. We reached out to the toxicology department to identify if there are any chances of acute or chronic toxicity related to our bacterial product and to explore biotherapeutic concerns regarding our treatment, like shelf life stability, potential for contamination, bacterial viability over time, and long-term environmental safety of our containment systems. This helped us follow safe laboratory practices and regulatory guidelines for live bacterial products. Our preclinical validation development ends with cross-validation, where our work will be reviewed by another laboratory, giving us a final assessment of our research progress and safety measures. By the end of this approach, our therapy will be ready for clinical studies.
We will develop the bacterial powder using the freeze-drying technique (which has a mathematical model; refer to the model page). L. plantarum will be grown in a suitable liquid culture medium until it reaches a high cell density. The bacterial cells will be then harvested, typically by centrifugation, to separate them from the spent culture medium. The harvested bacterial pellet will be resuspended in a solution containing cryoprotectants that consist of trehalose and sucrose, as well as skim milk, which are strong candidates for protecting L. plantarum during freeze-drying.
Subsequently, it will be stored in a freezer at -20°C to keep it alive for the longest period. (which has a mathematical model; refer to the model page). Then, the powder will be put in a capsule made from HPMC material with size 3. Additionally, we designed an inhaler with specific parameters to deliver the maximum percentage of the powder (which has a specific model to describe it; refer to the hardware page).
Moreover, to gain FDA approval for our therapeutic approach, we will need further steps than just preclinical testing. The clinical trials allow us to evaluate the safety and efficacy of a new drug or treatment in humans before it can be approved for use.
However, before that, we will need to apply for an Investigational New Drug (IND) / Clinical Trial Application (CTA) Submission that includes:
The blueprint for our protocol to conduct the trial will include study design, safety, dosing, interventions and participant eligibility.
The development of PRESS will ensure a GMP (good manufacturing practice). Adding on, it’s important to gather detailed documentation regarding the production of our approach and optimization for its delivery.
Analytical data for product quality, purity, and potency, which helps us to evaluate our CMC.
We will compile the results demonstrating the safety margin of our inhaler.
After receiving the IND approval, another mandatory step will be needed, which is the clinical trial phase. Additionally, there is a difference in the number of participants that will be based on the type of data needed from each stage:
This will include the smallest group and contain healthy volunteers. This stage primarily focuses on finding the safety, tolerability, and safe dose margins of the inhaler.
This phase will involve a larger group of participants to demonstrate preliminary efficacy and for further assessment of safety.
Even larger, it contains more randomized and controlled participants. The trial aims to reconfirm the efficacy and safety of our approach compared to a placebo. This trial helps us by interpreting the adverse reactions associated with different doses.
Maintaining our alignment with FDA guidelines including the laws regarding participant diversity, patient-focused design, and data transparency will guarantee our approval.
To bring PRESS to patients, we must comply with the U.S. Food, Drug, and Cosmetic Act (FD&C Act) and relevant FDA regulations (21 CFR Parts 200–299, 600–680). Our therapeutic approach will use an engineered L. Plantarum bacteria to be inhaled by MDI devices. FDA review will focus on the safety, efficacy and quality of the therapeutic strain and siRNA payload.
PRESS will be regulated as a biologic or drug product rather than as a new device. Before clinical use, an Investigational New Drug (IND) application must be submitted. This step will evaluate our safety to enter human trials and outline study design, dosing, and manufacturing controls.
Since our therapeutic approach will be built on using genetically modified Lactobacillus bacteria, our application will fall under the FDA’s biologics category. As a result, for our market authorization phase, we will submit a Biologics License Application (BLA) rather than a New Drug Application.
After BLA approval, the FDA will continue monitoring its use to detect any rare side effects to ensure long-term safety. Additionally, this post-market monitoring will evaluate our therapeutic consistency across patient populations.
Because PRESS uses a familiar inhaler platform, the regulatory spotlight stays on its safety, effectiveness, and real-world performance. This helps streamline the path to approval while keeping long-term patient safety at the center.
We still have to follow other regulatory procedures after the premarket submission is finished. Our team will ensure that the inhaler is included in the FDA database by registering our manufacturing establishment.
After commercialization, we will still need to continue demonstrating that PRESS is safe and effective over time since the FDA places a high priority on post-market surveillance after approval.
Our team will ensure its compliance with the most recent FDA guidelines, as we are sure that this adherence will not only uphold our approval but also foster confidence by guaranteeing long-term dependability, safety, and efficacy.
The backbone of asthma management till this day remains inhaled corticosteroids (ICS) like fluticasone and budesonide. As these drugs help control inflammation, they still bring side effects that range from oral thrush to more serious metabolic issues.
Another line of treatment made for those whose asthma remains uncontrolled with ICS and LABA is biological therapy. Drugs like omalizumab and tezepelumab target immunopathways and actually do bring relief for severe uncontrolled asthmatics. Unfortunately, they come at a high cost for the patient, as their prices usually range from $30,000 to $60,000 yearly. Additionally, patients with neutrophilic or steroid-resistant asthma may see little improvement, as these biologics can only target eosinophilic asthma.
A newer wave of research is focusing on RNA-based therapies. Companies like Zabecor (Excellair™, siRNA targeting Syk kinase) and Alnylam are testing siRNA approaches in respiratory disease. These represent a promising direction but remain in early clinical stages and are not yet widely accessible.
This is where PRESS introduces something new. It is the first therapeutic approach that is designed to deliver siRNA through engineered Lactobacillus plantarum directly into the lungs. PRESS targets the TSLP pathway, a major driver of severe asthma, but offers practical advantages: dosing only once or twice a year instead of daily inhalers or frequent injections, and the potential to lower overall healthcare costs by preventing exacerbations and hospital stays. Additionally, our financial analysis has highlighted that compared to other biological therapies, PRESS has the potential to be less costly per year for a patient. Refer to entrepreneurship financial analysis.
● For Patients:
Severe asthma lowers the quality of life for its patients. Its frequent attacks and daily inhalers make it hard for them to adhere well to their management. PRESS changes that. Just 1–2 capsules a year can bring long lasting control, increase adherence to treatment, and give patients back their quality of life.
● For Physicians:
Doctors often face frustration when patients fail to respond to steroids or lose their adherence. However, PRESS gives them a new option by being a simple, effective tool for the hardest-to-treat cases. With fewer doses and steady results, PRESS helps doctors deliver better care while easing the strain of repeated hospital visits.
● For Healthcare Systems:
Asthmatic patients' exacerbations are expensive as they often require emergency visits, hospital stays and impose long-term complications. By cutting down these events, PRESS lowers costs and frees up resources. It also offers a more affordable alternative to costly biologics, making access easier within insurance frameworks.
● For the Economy:
Uncontrolled asthma keeps people out of work and lowers productivity. PRESS can help stabilize patients, which means fewer sick days, healthier workers, and stronger long-term economic output.
● For the Environment:
Most inhalers mean constant refills and growing medical waste. PRESS requires far fewer doses, reducing waste and aligning with global sustainability goals in healthcare.
Our target is to give the severe asthmatic patients a better solution through our novel inhaler-PRESS that helps reduce asthma symptoms on the long term without reaching out to other current treatments, which can be more expensive, offer less efficacy and potentially more side effects. This will occur via a proper management plan, adherence to PRESS and more essentially applying a suitable lifestyle for the patient.
