Every breakthrough in medicine begins with a question: “How can we do better for patients?”. In Chronic Lymphocytic Leukemia (CLL), patients face many challenges from off target effects of their treatments to resistance and relapse over time. These limitations call for the design of more advanced therapeutic approaches that are both effective and dont restrict patients in everyday life.

siREN steps in as an answer to those needs. By combining a dual target RNA interference therapy with lipid nanoparticle carriers, designed to target only the CLL cells, we aim to offer a more effective and precise therapeutic option. However, to ensure that siREN can one day reach the patients, we embraced entrepreneurship as a critical part of our journey. Through this work we explored how our project could evolve into a viable solution, transforming patient care.

Chronic Lymphocytic Leukemia is the most common adult leukemia in Western countries, representing 22–30% of all leukemia cases ¹ and with an average crude incidence rate across Europe of 4.8 per 100,000 people ², although the true incidence is unknown as many patients are asymptomatic. Based on data of CLL between 1990 to 2019 from the Global Burden of Disease (GBD) study 2019, the global burden of CLL has increased dramatically, with over 100,000 incidence cases and over 40,000 death cases globally reported in 2019. In Europe, median age at diagnosis is 71 years in men and 74 years in women ³, with an approximately twice as high of an incidence in males than in females. Although CLL is indolent, it shortens survival in the elderly. ³ Epidemiological studies found that the incidence of CLL rises exponentially with age and reaches a peak in elderly populations.

Despite the development of targeted therapies such as BTK and BCL2 inhibitors, CLL remains incurable. Patients have to face many challenges with the off targets of their treatments as you can see on table1, affecting their everyday life. Moreover, they can relapse or develop resistance to their treatments over time. These limitations highlight that there is a clear unmet need in the treatment landscape of CLL. There is an urgent demand for therapies that are effective with limited off targets and are manufactured at scale and cost efficiently.

siREN is a targeted, dual-siRNA therapeutic platform designed to silence two critical drivers of CLL pathogenesis - BCL-2 and BTK - simultaneously. This dual approach disrupts complementary oncogenic pathways, restores apoptotic signaling, and inhibits malignant B-cell proliferation. The siRNAs are encapsulated within a proprietary lipid nanoparticle (LNP) system functionalized with monoclonal antibodies against ROR1, ensuring selective delivery to CLL cells while minimizing interaction with healthy tissues.

Key Innovations and Competitive Advantages

Value Creation

Value proposition Canvas

In order to translate siREN, from a research project to a viable therapy , we developed a business model Canvas. This framework allowed us to identify our key stakeholders, clarify our value proposition, and outline potential pathways for siREN’s development and commercialization. Our analysis showed that siREN could be introduced through partnerships with hospitals and pharmaceutical companies, targeting relapsed and refractory CLL patients as the initial customer segment. In the long term, siREN can expand as a platform technology adaptable to other cancers, creating opportunities for growth beyond CLL.

The scientific landscape of Chronic Lymphocytic Leukemia (CLL) has grown significantly in recent years, yet there are still gaps that recent and more precise treatments try to cover. The Global Market for CLL therapies was valued at approximately US 5.4 billion USD in 2025 and is projected to reach nearly 7.5 billion USD by 2030 ¹⁵. This figure represents the Total Addressable Market (TAM), the global opportunity for all companies developing CLL therapies.

From this broader figure, the Servisable Available Market (SAM) can be narrowed to relapsed and refractory CLL patients. Current therapies such as BTK and BCL2 inhibitors are highly effective initially, but patients can develop resistance over time, leading to treatment failure. Clinical trials have demonstrated that targeted therapies such as BTK inhibitors significantly improve outcomes for CLL patients ⁷. However, resistance remains a major challenge. Mechanistic studies identified mutations in BTK and PLCG2 as the principal causes of resistance to ibrutinib ¹⁶. Long-term follow-up and real-world data indicate that approximately 20–30% of patients discontinue BTK inhibitor therapy within 3–5 years due to disease progression or intolerance []. Applying this percentage to the total CLL therapeutics market¹⁷¹⁸, the SAM for relapsed and refractory patients can be estimated at 1.1–1.6 billion USD annually.

The Serviceable Obtainable Market (SOM) represents the portion that siREN could realistically capture during early clinical adoption. Given that novel therapies typically enter the market gradually through specialized oncology centers and partnerships with pharmaceutical companies, a reasonable initial estimate would be 1–5% of the SAM within the first years of commercialization. This corresponds to 10–80 million USD annually, depending on regional focus and uptake speed. The SOM could expand significantly if siREN proves to be safe, effective, and scalable, and if its platform is extended to other malignancies expressing ROR1.

siREN is a biotechnology start-up focusing on developing RNAi therapies for blood malignancies, starting with Chronic Lymphocytic Leukemia. Originating from iGEM Thessaloniki 2025 the company builds on academic expertise to advance a dual siRNA therapy delivered by lipid nanoparticles, designed to target only the cancerous cells. Our mission is to address resistance and relapse in CLL treatment, through a precise and scalable therapeutic platform.

Vision-Mission-Values

SPIN OFF ESTABLISHMENT

The Team

At siREN our strength lies in our people. We are a multidisciplinary team, combining science, engineering and entrepreneurship. From laboratory research to business development, every role in our structure is designed to support our mission of transforming RNA interference into a real therapeutic option for patients.

Executive Leadership

Ioanna Karampela

Chief Executive Officer (CEO)

Aggeliki Iordanidou

Chief Scientific Officer (CSO)

Margarita Papastergiou

Chief Operating Officer (COO)

Scientific & Technical Teams

Errika Sylai

Molecular Biology Unit

siRNA design, in-vitro validation, MoA

Erriketti Theodora Moumka

Nanoparticle Engineering Unit

LNP formulation, optimization, targeting

Antonios Tsiorvas

Computational Biology & Modeling

Efficacy prediction, structural modeling

Kyriakos Marios Papamanolis

Technical Staff

Lab support, instrumentation

Business & Translation Teams

Marianna Rafailia Palieraki

Business Dev. & Partnerships

Olga Anna Skarlatou

Finance & Administration

Giorgos Zekas

Communications & Outreach

Georgios Bousmalis-Maroulis

Social Media Staff

New Hire

Regulatory & Clinical Affairs

SWOT Analysis

To evaluate siREN’s entrepreneurial potential we performed a SWOT analysis. This framework allowed us to identify the internal strengths and weaknesses of our therapeutic concept, as well as the external opportunities and threats that could influence its development and commercialization.

Strengths

• Dual-target RNAi approach (BCL2 + BTK) designed to overcome resistance.
• ROR1-targeted lipid nanoparticles for cancer-cell specificity.
• Builds on clinically validated RNAi/LNP platforms.
• Modular design adaptable to other cancers.

Weaknesses

• Early-stage concept with no in vivo validation yet.
• High development costs in oncology.
• Competitive IP landscape in RNAi and LNP delivery.

Opportunities

• Growing CLL therapeutics market with clear unmet need.
• B2B partnerships, licensing, and co-development potential.
• Platform scalability into other ROR1+ cancers.

Threats

• Competition from BTKi, CAR-T, and bispecific antibodies.
• High costs and long oncology trial timelines.
• Potential unforeseen safety or delivery challenges.

PEST Analysis

In addition to assessing siREN’s internal strengths and weaknesses, we examined the external environment that could influence its development and market potential. A PEST analysis considers the Political, Economic, Social, and Technological factors shaping the biotechnology and oncology landscape. This framework allowed us to identify external drivers and challenges that may affect siREN’s translation from a research project into a therapeutic product.

Political

• Favorable regulatory incentives for rare and orphan diseases in the EU and U.S.
• Complex and lengthy oncology approval process may slow siREN’s development.
• Differences in healthcare regulations across regions (EU, U.S., Asia) affect approval and reimbursement.

Economic

• Global CLL therapeutics market > USD 5 billion and growing, attractive for investors and pharma partners.
• Substantial upfront investment required (tens to hundreds of millions).
• Pricing and reimbursement negotiations could limit profitability unless siREN proves cost-effectiveness.

Social

• Growing demand for therapies with fewer side effects and improved quality of life.
• CLL patient advocacy groups influence adoption, lobbying for faster approval and coverage.
• Ethical concerns about accessibility: risk of availability only in high-income countries.

Technological

• RNAi therapies already clinically validated (e.g., patisiran, givosiran).
• Lipid nanoparticles (LNPs) proven scalable through mRNA vaccines.
• Further innovation needed in targeted delivery; siREN’s ROR1 strategy must show in vivo safety/selectivity.

RISK Assessment

STRATEGIC GOALS

EXIT STRATEGY

PITCH DEMO

To effectively communicate the vision and innovation behind our project, we created a Pitch Demo Video that presents siREN. The video aims to introduce our project in a concise, engaging, and visually compelling way, highlighting both its scientific foundation and entrepreneurial potential.

siREN Therapy Classification

siREN is an RNA interference (RNAi)-based therapeutic designed for the treatment of Chronic Lymphocytic Leukemia (CLL). It uses small interfering RNAs (siRNAs) to silence the overexpression of two key oncogenes, BCL-2 and BTK, delivered via lipid nanoparticles (LNPs) functionalized with anti-ROR1 antibodies for targeted delivery to CLL cells.

The therapy’s classification determines the regulatory pathway, approval process, and development requirements. Based on guidance from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), siREN is classified as follows:

Together, these steps create a clear roadmap for siREN to move from preclinical research to first-in-human testing. Early engagement with regulators, strong quality documentation, and harmonized safety planning will be the key to guiding our therapy safely and effectively into the clinic.

Intellectual Property Strategy

For siREN to be translated from an academic concept into a marketable therapy, securing strong intellectual property (IP) protection is essential. The development of a dual siRNA therapeutic delivered by targeted lipid nanoparticles involves novel combinations of sequence design, delivery formulation, and targeting strategies. Protecting these innovations through patents not only safeguards the scientific work but also makes siREN more attractive to pharmaceutical partners and investors. The path to acquiring IP typically unfolds in several stages:

Developing an innovative therapy such as siREN requires not only strong scientific foundations but also careful financial planning. Translating a dual siRNA–LNP therapeutic platform into the clinic involves significant investments in infrastructure, personnel, preclinical and clinical studies, as well as regulatory and intellectual property processes. To evaluate the feasibility of siREN’s entrepreneurial path, we created a staged financial roadmap. This roadmap outlines the expected costs for the first six months, the following five years, and the long-term ten-year horizon, assuming a team size of 11–15 members. By breaking down major expenses such as equipment, salaries, consumables, clinical development, and IP acquisition, we provide a clear picture of the resources required to bring siREN from concept to commercialization.

Our discussions with clinical experts and entrepreneurship mentors were instrumental in shaping siREN’s translational and business strategy. Through meetings with Dr. Katodritou (Hematology Specialist at Theagenio Cancer Hospital) and Dr. Touroutoglou (Hematologist-Oncologist), we gained critical insights into the limitations of existing CLL therapies, the unmet clinical needs, and the importance of developing patient-tailored, low-toxicity solutions. Complementing the clinical perspective, entrepreneurship mentors such as Dr. Lerios, and Mr. Komselis and Dr. Kafetzopoulos guided us in transforming our scientific innovation into a sustainable business model. Their expertise in strategy, and startup development helped us refine siREN’s value proposition, market positioning, and commercialization roadmap, bridging the gap between research and real-world impact.

NGO and Institutional Partnerships

To ensure siREN’s growth within a socially responsible framework, we are establishing partnerships with NGOs, educational institutions, and medical associations. Through targeted workshops and awareness initiatives, we aim to enhance public understanding of CLL and foster supportive community attitudes. Our organizational model promotes gender equality and inclusion, offering opportunities for individuals with disabilities in suitable professional roles. Continuous collaboration with CLL patient associations and healthcare professionals ensures that siREN evolves in line with real patient needs and clinical feedback, merging scientific innovation with social impact.

Our project siREN aligns with several United Nations Sustainable Development Goals (SDGs) by integrating scientific innovation with social impact. Through our RNAi-based therapeutic for CLL, we advance Good Health and Well-Being (Goal 3), while our inclusive educational initiatives promote Quality Education (Goal 4) and Gender Equality (Goal 5). By fostering entrepreneurship, innovation, and skill development, we contribute to Decent Work and Economic Growth (Goal 8) and Industry, Innovation, and Infrastructure (Goal 9). Our focus on accessibility and sustainability supports Reduced Inequalities (Goal 10) and Climate Action (Goal 13), while our extensive collaborations across academia, healthcare, and NGOs embody Partnerships for the Goals (Goal 17).

Walk AUTh Startups Bootcamp

On May 23–25, our team had the opportunity to participate in the Walk AUTh Startups Bootcamp, hosted at Aristotle University of Thessaloniki. The competition gathered numerous student teams, each presenting their own entrepreneurial ideas.

We took part in the event with our project siREN, which serves as the foundation of our startup concept. During the three day bootcamp, we developed a business plan and shaped the structure of our startup, while receiving valuable coaching and mentorship from entrepreneurship experts. These experts guided us throughout the process, challenged us with critical questions, and helped us refine our business strategy and model.

Among the key issues we addressed were how our company could enter the market, what its structure should look like, who our potential target audience would be, and what exact product we would deliver. This process proved to be both a challenge and a real-world simulation, allowing us to confront practical aspects of building a sustainable business.

By the end of the bootcamp, after submitting our deliverables, we presented our idea and business model among the competition's finalists and ultimately and our proposal was distinguished among the top 7 most mature and promising ideas of the competition, an achievement that reinforced our commitment to developing siREN into a viable startup.

Falling Walls Lab DAAD Greece

On September 19, 2025, our team proudly participated in the Falling Walls Lab DAAD Greece, a prestigious entrepreneurship competition and networking forum. Falling Walls Lab is a global platform that highlights groundbreaking ideas and connects a diverse, interdisciplinary community of students and young professionals. Throughout the year, renowned academic institutions across the world host these Labs to showcase the creativity, passion, and impact of some of the most innovative minds in their fields.

Each participant is given just three minutes to pitch solutions to some of today’s most pressing challenges in front of a distinguished jury of academics, business experts, scientists, and an engaged audience. Around one-third of these international Labs are organized by the German Academic Exchange Service (DAAD).

Our team entered the competition by presenting the business model of our startup, carefully structured to address real-world challenges while highlighting the value of our innovative project. In this highly competitive environment, we delivered our pitch, showcasing both our entrepreneurial vision and the scalability of our business model. Among many strong contestants, our team achieved a remarkable distinction: we were awarded 3rd place. This recognition not only honored our efforts but also gave us additional motivation to refine and perfect our business design and our overall idea.