Ioanna Karampela
Chief Executive Officer (CEO)
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.
| Drug | Common Side Effects | Serious/Unique |
| Venetoclax | Neutropenia, anemia, diarrhea, nausea, fatigue, upper respiratory tract infections 4 5 | Tumor Lysis Syndrome (TLS), rapid tumor breakdown causing dangerous electrolyte shifts, especially during dose ramp-up 4 5 |
| Ibrutinib | Neutropenia, thrombocytopenia, diarrhea, rash, arthralgia, fatigue, infections 6 7 | Bleeding , atrial fibrillation, hypertension 6 8 |
| Acalabrutinib | Neutropenia, anemia, thrombocytopenia, headache, diarrhea, fatigue, cough, myalgia 9 | Bleeding; atrial fibrillation and hypertension less frequent than ibrutinib 9 |
| Idelalisib | Neutropenia, anemia, thrombocytopenia, diarrhea, nausea, fever, fatigue, cough 10 11 | Severe diarrhea/colitis, hepatotoxicity, pneumonitis, intestinal perforation 10 11 |
| Treatment | Study & Patient Group | How Long it Controlled the Disease (PFS) |
| Venetoclax + Rituximab (Ven-R) | MURANO trial12 | Median ~53 months without disease getting worse vs 17 months for chemo-immunotherapy12 |
| Venetoclax + Obinutuzumab (Ven-Obi) | CLL14 trial13 | Median ~76 months before relapse 13 |
| Ibrutinib (first-generation BTK inhibitor) | RESONATE trial & real-world data 7 | Median ~44 months in relapsed CLL; longer in untreated 7 |
| Acalabrutinib | ASCEND trial14 | Median not reached after 22 months of follow-up 14 |
| Idelalisib + Rituximab | Relapsed CLL 11 | Median ~20 months 11 |
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.
A novel therapeutic mechanism simultaneously downregulating BCL-2 and BTK, two critical and complementary drivers of CLL cell survival. This dual inhibition disrupts distinct oncogenic pathways, significantly enhancing apoptotic induction and reducing the likelihood of treatment resistance compared to single-target approaches.
Proprietary LNP formulation optimized for siRNA stability, circulation time, and intracellular delivery efficiency. The system facilitates effective endosomal escape and cytosolic release, ensuring robust target gene knockdown in malignant cells.
Functionalization of LNPs with monoclonal antibodies against ROR1, an oncofetal receptor selectively expressed in CLL cells and absent in normal adult tissues. This targeting strategy maximizes therapeutic precision, minimizes off-target uptake, and reduces systemic toxicity.
Specifically designed for patients who have developed resistance to both BTK and BCL-2 inhibitors, a population with extremely limited treatment options and high unmet clinical need.
The delivery and targeting framework is adaptable to other malignancies by substituting siRNA sequences and antibody ligands, enabling expansion into additional oncology indications and strategic partnerships.
A precise therapy with fewer side effects, improved efficacy, and new hope for drug-resistant CLL.
An innovative option that integrates into current protocols while overcoming resistance.
Potential to lower long-term costs by reducing hospitalizations, cycles, and complications.
| Dimension | siREN (proposed) | Venetoclax | Ibrutinib | CAR‑T (liso‑cel / Breyanzi) |
| Modality / Target | Dual siRNA against BCL2 & BTK, delivered via LNPs; ROR1‑directed targeting to CLL cells (antibody‑functionalized LNPs). | Small‑molecule BCL‑2 inhibitor (induces apoptosis of B‑cells). | Small‑molecule BTK inhibitor (blocks BCR signaling). | Autologous CD19 CAR‑T cell therapy. |
| Intended Use | Relapsed/refractory CLL, incl. post‑BTKi/BCL2i resistance; platform for combinations. | Frontline and R/R CLL in fixed‑duration or combo regimens per label/Guidelines. | Frontline and R/R CLL . | FDA‑approved (Mar 2024) for adults with R/R CLL/SLL after BTKi and BCL2i |
| Selectivity | Tumor‑addressing via ROR1 (minimal normal adult tissue expression → potential to lower off‑tumor effects). To be clinically validated. | BCL‑2 expressed broadly in lymphoid cells; on‑target tumor lysis risk. | BTK in normal B‑cells & platelets; on‑target immune/hemostasis effects. | CD19 on normal B‑cells → predictable B‑cell aplasia (managed with IVIG). |
| Administration | IV (or potentially SC) LNP infusion; finite cycles envisioned. | Oral tablets; ramp‑up then daily (often finite‑duration combo). | Oral, continuous daily. | One‑time leukapheresis → manufacturing → lymphodepletion → single infusion; inpatient‑capable centers. |
| Onset / Depth of Response | Anticipated rapid target knockdown; dual‑pathway hit may deepen apoptosis vs mono‑target. Preclinical/clinical data pending. | Rapid debulking possible; deep MRD‑negative remissions in combos; needs careful start. | High response rates; durability varies; resistance and intolerance can emerge. | Potential for durable remissions in double‑refractory CLL/SLL. |
| Key Risks / Toxicities | LNP‑class: infusion reactions, transient LFT elevation; siRNA off‑target minimized via sequence/design + ROR1 targeting (to be shown). | Tumor Lysis Syndrome (TLS) risk at initiation → requires 5‑week ramp‑up & prophylaxis/monitoring. | Atrial fibrillation, bleeding, hypertension; discontinuations not rare. | CRS and ICANS; requires REMS‑level monitoring/experienced centers. (Per product labeling/approvals.) |
| Monitoring Burden | Moderate (infusion monitoring; pharmacodynamic markers for BCL2/BTK mRNA/protein). | High at start (TLS labs, hydration), then routine. | Ongoing CV/blood pressure/bleeding risk monitoring. | Intensive peri‑infusion monitoring (CRS/ICANS), hospitalization capacity. |
| Logistics / Time‑to‑Treat | Off‑the‑shelf drug product once manufactured; no patient‑specific production. | Immediate (retail/specialty pharmacy once cleared). | Immediate (retail/specialty pharmacy once cleared). | Weeks for cell manufacturing; complex supply chain. |
| Treatment Duration / Cost Profile | Finite course envisioned; cost tied to limited cycles; scalable manufacturing (LNPs). | Often finite in combos (e.g., 12–24 months) → drug/accompaniment costs; lab start‑up overhead. | Indefinite therapy until progression/intolerance → cumulative cost. | One‑time, high upfront cost; potential long‑term remission offsets. |
| Resistance Risk | Dual‑pathway silencing designed to lower resistance vs mono‑target agents; sequences can be retargeted if escape variants arise. | BCL‑2 mutations/clonal shifts can drive resistance. | BTK/PLCγ2 mutations and intolerance are common resistance drivers. | Different failure biology (antigen loss/T‑cell exhaustion); retreatment options evolving. |
| Scalability / Platform | Modular: swap siRNAs/antibodies to expand to other indications (ROR1+ tumors or other targets). | Indication‑specific; limited platform spillover. | Class platform exists (other BTKi), but single‑target. | Autologous, complex to scale; allogeneic under development (not CLL‑approved). |
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.
Our mission is to develop a RNAi therapy to address the unmet needs of patients with Chronic Lymphocytic Leukemia. By combining dual-target siRNA design with ROR1-directed lipid nanoparticle delivery, we aim to create precise, effective, and safe therapies that overcome resistance and relapse.
Our vision is to establish siREN as a pioneering biotechnology platform that expands beyond CLL to other cancers, delivering targeted RNAi solutions with global impact. As a B2B start up we aspire to collaborate with pharmaceutical companies to bring these therapies in the market.
In siREN every decision is guided by the goal of improving patient quality of life. We deeply value diversity, accessibility and ethical experimentation. We strive to foster innovation through collaboration, uniting expertise from academia, industry, and patient communities.
siREN is envisioned as a biotechnology spin-off originating from the research ecosystem of the Aristotle University of Thessaloniki (AUTH). AUTH, as the largest university in Greece, actively supports technology transfer and entrepreneurship through the Technology Transfer Office (TTO) and the Special Account for Research Funds (ELKE). These units provide guidance in intellectual property protection, licensing agreements, and the establishment of spin-off companies that commercialize academic research.
Researchers submit their innovation to the AUTH TTO, which evaluates novelty, market potential, and patentability.
If suitable, patents or other forms of IP are filed in collaboration with the university, ensuring institutional ownership and inventor rights.
A commercialization strategy is prepared, including market analysis, funding prospects, and partnership models.
The university’s governing bodies review the proposal under the framework of Greek Law 4864/2021, which regulates academic spin-offs.
Once approved, the spin-off is legally established as an independent entity, with AUTH often retaining a minority shareholding, while researchers and investors form the core management team.
Through this process, siREN could transition from a student-led iGEM project to an official biotechnology company. The connection to AUTH ensures that the spin-off maintains strong scientific roots while gaining the legal and business framework required for growth. Establishing siREN as an AUTH spin-off would also facilitate access to national and European funding programs, while strengthening collaborations with hospitals, pharmaceutical companies, and international research partners.
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.
Chief Executive Officer (CEO)
Chief Scientific Officer (CSO)
Chief Operating Officer (COO)
Molecular Biology Unit
siRNA design, in-vitro validation, MoA
Nanoparticle Engineering Unit
LNP formulation, optimization, targeting
Computational Biology & Modeling
Efficacy prediction, structural modeling
Technical Staff
Lab support, instrumentation
Business Dev. & Partnerships
Finance & Administration
Communications & Outreach
Social Media Staff
Regulatory & Clinical Affairs
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.
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.
| CATEGORY | RISK | IMPACT | MITIGATION |
| Scientific & Technical | siRNA may show limited efficacy in vivo or off-target effects. | Reduced therapeutic potential, possible safety concerns. | Employ computational modeling to redesign siRNAs for lab validation. |
| LNP delivery may not achieve sufficient specificity for CLL cells. | Unintended uptake by healthy cells, reduced therapeutic potential. | Optimize formulation with in silico modeling. | |
| Regulatory | Delays or failures in obtaining regulatory approval (EMA/FDA). | Increased costs, longer time-to-market. | Seek early orphan drug designation, engage with regulators from preclinical stages. |
| IP challenges (overlap with siRNA or LNP patents). | Legal disputes, restricted commercialization. | Conduct thorough FTO searches and file patents via AUTH TTO/WIPO. | |
| Financial | High cost of clinical development. | Funding gap, inability to complete trials independently. | Secure EU grants and venture funding during early phases. |
| Dependence on external investors. | Potential loss of control over company strategy. | Diversify funding streams (public grants, partnerships, AUTH support). | |
| Market | Competing therapies (BTK inhibitors, CAR-T, etc.). | Market saturation, reduced adoption. | Position siREN as complementary therapy for resistant/relapsed CLL. |
| Small patient population. | Limited commercial return. | Expand to other ROR1+ malignancies. |
For siREN, an exit strategy is not about ending the journey but about ensuring that our therapeutic innovation reaches patients in the most effective and scalable way. In biotechnology, exits typically occur through licensing agreements, strategic acquisitions, or public offerings. We have identified three potential pathways:
Given the high costs of late-stage clinical trials, licensing siREN’s dual-target RNAi therapy to a larger pharmaceutical partner represents a sustainable strategy. Through licensing, siREN would transfer clinical development and commercialization responsibilities while retaining royalty streams and milestone payments.
Many biotech startups exit through acquisition once early clinical data demonstrate proof of concept. A strategic acquisition would allow siREN to integrate into an established oncology pipeline, accelerating Phase III trials and global distribution.
Although less common for small European biotech ventures, an IPO could provide siREN with the capital needed to independently advance late-stage trials and maintain control over commercialization. This option would be considered only after demonstrating strong clinical data and securing a robust investor base.
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 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:
In the United States, siREN would be considered a therapeutic oligonucleotide, falling under the oversight of the Food and Drug Administration (FDA). Regulation is primarily conducted by the Center for Drug Evaluation and Research (CDER) through the New Drug Application (NDA) pathway.
If siREN’s antibody-targeted LNP delivery system is considered to contribute a biological component of critical therapeutic function, the product may alternatively fall under the Center for Biologics Evaluation and Research (CBER), requiring approval through a Biologics License Application (BLA).
This classification aligns with existing FDA precedents, such as the approval of siRNA therapies Patisiran (the first LNP-based siRNA drug) (), Givosiran (), Inclisiran (), and Vutrisiran (). Like these therapies, siREN could also be eligible for expedited approval pathways, including Breakthrough Therapy Designation, if early clinical evidence demonstrates significant benefit compared to current treatments for relapsed or resistant CLL.
Within the European Union, siREN would be classified as a medicinal product under the European Medicines Agency (EMA). Chemically synthesized siRNAs are generally regulated as conventional medicines, whereas siRNAs or delivery platforms that incorporate biological components (such as antibody-conjugated nanoparticles) may fall under the scope of biological medicinal products.
Oversight is conducted through the Committee for Medicinal Products for Human Use (CHMP) under the centralized approval process. Depending on the level of biological engineering incorporated into future versions of siREN, it may also be evaluated for classification as an Advanced Therapy Medicinal Product (ATMP), particularly if it integrates novel or cell-based delivery strategies.
To accelerate development, siREN could also apply for PRIME (PRIority MEdicines) designation, which is reserved for innovative therapies addressing high unmet medical needs. This pathway would provide early regulatory guidance and support, facilitating a more efficient route to patient access.
Bringing siREN from the lab into the clinic means navigating well-defined regulatory pathways in both the United States and the European Union. Because siREN combines synthetic siRNA, a lipid nanoparticle (LNP) delivery system, and antibody targeting, it follows the rules that apply both to oligonucleotide drugs and advanced biologics.
In the United States, the process begins with early conversations with the Food and Drug Administration (FDA). A pre-IND meeting allows teams to align with regulators on how siRNA and LNPs should be manufactured and tested, what nonclinical studies are essential, and how the first-in-human trial should be designed.
The IND application itself includes administrative forms, the clinical protocol, an Investigator’s Brochure, detailed quality information about the siRNA and the LNP formulation, and results from preclinical pharmacology and toxicology studies. Once submitted, the FDA has thirty days to review the IND before a trial can begin.
During the trial, sponsors must report serious and unexpected adverse events, provide annual updates, and submit amendments if the protocol or manufacturing details change.
In the European Union, trials are authorized under the Clinical Trials Regulation through the Clinical Trials Information System (CTIS). As in the U.S., early scientific advice is recommended so that CMC and safety expectations are clearly stated from the start.
The CTA dossier is divided into a scientific part, which includes the protocol, Investigator’s Brochure, and Investigational Medicinal Product Dossier (IMPD), and a national part, which covers consent forms, site suitability, and insurance. Review is centralized across EU member states, with strict timelines that usually allow a decision within two to three months.
Safety is reported through the EudraVigilance system, and annual Development Safety Update Reports are required. Any substantial modifications must be filed in CTIS, and transparency rules ensure that trial information and results are publicly shared.
For siREN, regulators on both sides of the Atlantic will expect a strong focus on quality and safety. This means defining critical quality attributes of the siRNAs, characterizing impurities, ensuring stability of the LNP formulation, and validating the antibody conjugation strategy. The nonclinical studies will need to cover repeat-dose toxicity, potential immune stimulation and complement activation as well as risks.
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.
First-in-Human, Phase 1/2a Study of siREN: A Dual siRNA Therapeutic Targeting BCL-2 and BTK in Patients with Relapsed or Treatment-Resistant Chronic Lymphocytic Leukemia (CLL)
siREN is an investigational RNA interference (RNAi) therapy designed to silence the overexpression of BCL-2 and BTK, two critical survival drivers in CLL. Delivered via lipid nanoparticles (LNPs) functionalized with anti-ROR1 antibodies, siREN aims for selective targeting of malignant CLL cells while sparing healthy tissues.
| Year | Stage | Key Activities | Regulatory Milestones |
| 2025 (H2) | Preclinical – Proof of Concept | - Complete in-vitro efficacy studies in primary CLL cells. - Conduct in-vitro off-target screening & immunogenicity assessment. - Initial in-vivo PK and biodistribution in murine models. - Preliminary safety in rodent models. | - Early Scientific Advice meeting (EMA). - Pre-IND meeting (FDA) to discuss CMC, nonclinical plan, and trial design. |
| 2026 (H1–H2) | Preclinical – IND/CTA Enabling | - GLP toxicology in rodent + non-rodent species. - Repeat-dose toxicity, safety pharmacology, and genotoxicity studies. - LNP stability, manufacturing scale-up, and quality control validation. - Complete final Investigator’s Brochure (IB) and Investigational Medicinal Product Dossier (IMPD). | - Submit IND to FDA (late 2026). - Submit CTA via CTIS to EMA (late 2026). |
| 2027 (H1–H2) | Phase 1 – First-in-Human (FIH) | - Multi-center, open-label dose escalation in adults with relapsed/refractory CLL. - 3+3 design, 3–6 dose levels. - Primary endpoints: safety, MTD/RP2D. - Secondary endpoints: PK, target engagement, preliminary efficacy. - Sites in both U.S. and EU to run under harmonized protocol. | - Ongoing SUSAR reporting (FDA & EMA timelines). - Annual IND Report (FDA) / DSUR (EMA). |
| 2028–2029 | Phase 2a – Expansion Cohorts | - Treat additional patients at RP2D to further evaluate safety and efficacy. - Cohorts may include high-risk genetic subgroups (e.g., TP53 mutation). - Primary endpoint: overall response rate (ORR). - Secondary endpoints: progression-free survival (PFS), molecular response rates. | - Interim meetings with FDA/EMA to review safety/efficacy data and discuss Phase 2b/3 planning. |
| 2030–2031 | Phase 2b/3 – Pivotal | - Randomized, controlled trial vs. best available therapy in relapsed/refractory CLL. - Larger, multi-national enrollment (~200–400 patients). - Primary endpoint: PFS. - Key secondary: overall survival (OS), duration of response, quality of life. | - Apply for Breakthrough Therapy Designation (FDA) / PRIME (EMA) if interim data show substantial benefit. - Potential for rolling submission of BLA/NDA (FDA) and MAA (EMA). |
| 2032 | Regulatory Submission | - Prepare and submit New Drug Application (NDA) or Biologics License Application (BLA) to FDA. - Submit Marketing Authorisation Application (MAA) to EMA under the centralized procedure. | - Regulatory review & potential accelerated approval pathways. |
| 2033 | Market Entry & Phase 4 (Post-Marketing) | - Post-marketing safety surveillance. - Additional studies in earlier-line CLL or combination regimens. - Long-term follow-up for survival and safety. | - Fulfill post-marketing commitments. - Ongoing pharmacovigilance per FDA/EMA requirements. |
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:
The first step is to assess the existing IP landscape. This involves reviewing published patents and scientific literature to identify whether similar siRNA designs, LNP formulations, or targeting approaches (e.g., ROR1-directed delivery) are already protected. A freedom-to-operate (FTO) analysis helps to determine whether siREN infringes on existing patents and where opportunities for novel claims exist.
Once potential novelty is identified, the team prepares an invention disclosure, documenting the unique features of siREN that could be patentable. This includes experimental evidence (e.g., downregulation of BCL2 and BTK, transfection data, selective targeting rationale) and computational models that strengthen claims. The disclosure is usually filed through the university’s Technology Transfer Office (TTO), which evaluates patentability and commercial potential.
A provisional application establishes an early filing date (priority date) without requiring a full patent draft. It gives siREN one year of protection while providing time to refine data, strengthen claims, and seek funding. During this period, results from additional experiments can be used to broaden and solidify the IP claims.
Within twelve months of the provisional filing, a non-provisional (full) application must be submitted to patent offices (such as USPTO or EPO). This step requires precise claim language, legal drafting, and supporting data to secure protection. At this stage, international protection strategies are considered, for example through the Patent Cooperation Treaty (PCT), allowing siREN to pursue patents in multiple jurisdictions simultaneously.
The patent office will examine the claims, often requesting clarifications or narrowing of scope. Responding effectively during prosecution is crucial to ensure broad and enforceable coverage. Once granted, patents must be maintained through periodic fees, and additional patents may be filed as siREN expands into new therapeutic areas.
Before developing our therapeutic approach, it was critical to map the current intellectual property and scientific landscape. This table showcase the key patents, applications and publications related to ROR1 based delivery system and siRNAs therapeutics. By identifying what has already been claimed we can better define the novelty of our approach and highlight opportunities for innovation.
| Doc (year) | Jurisdiction / Status | Assignee / Authors | What it claims / teaches (plain-English) |
| US 10,335,496 B2 – ROR1 antibody immunoconjugates (2019) | US granted | Oncternal (historically linked IP) | Antibodies to ROR1 as targeting moieties for delivering payloads (immunoconjugates/ADCs). Payloads are broad (cytotoxins etc.). patents.google.com |
| WO 2017/072361 – Anti-ROR1 antibodies (2017) | PCT (family in US/EU) | Univ./inventors (CAR-T/ligands) | Human/humanized anti-ROR1 Abs, CARs, and immunoligand-drug conjugates targeting ROR1. patents.google.com |
| KR 2021-028544 A – ROR1-targeted ADCs (2021) | KR published | (ADC assignee) | ADC against ROR1 with tubulin-disruptor payloads; methods & use in ROR1+ cancers. patents.google.com |
| US 2023/0405146 – Antibody-conjugated nanoparticles (2023) | US application | (Various inventors) | Nanoparticles conjugated to antibodies for targeted delivery; mentions ROR1 as one possible target. Payloads can include nucleic acids. patents.justia.com |
| EP 4045021 A1 – LNP for CAR mRNA / nucleic acids (2022) | EP published | (BioNTech-like landscape) | LNP compositions delivering mRNA/NA to selected cells; modular targeting ideas. Not ROR1-specific. patents.google.com |
| US 2020/0093936 – Therapeutic targeting of LNPs (2020) | US application | U Penn et al. | Targeted LNPs via conjugated ligands/Abs to endothelial markers; platform claims on targeting domain + LNP architecture. patents.google.com |
| Review: Anti-ROR1 ADC development (2021) | Article | Peng et al. | Summarizes anti-ROR1 ADC designs, linkers, payloads; shows clinical momentum. |
| Preclinical: huXBR1-402-G5-PNU (ROR1-ADC) (2021) | Article | Hu et al. | ROR1-targeted ADC efficacy in ALL/MCL models. |
| Context: VLS-101 (zilovertamab vedotin) | Pipeline/briefs | VelosBio/Merck | ROR1-targeting ADC (mAb-MMAE). |
| siRNA delivery (general landscape) | Review | Charbe 2020; Jung 2022 | siRNA delivery vectors, LNP behaviors, organ tropism. |
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.
| Equipment and Setup | 550-600K |
| Salary | 200-250K |
| Consumables | 85-90K |
| Rent and Utilities | 30-50K |
| IP Strategy | 0.5-1M |
| Salary | 9-11M |
| Consumables | 4-4.5M |
| Rent and Utilities | 1.5-2M |
| Clinical Phase I/II | 18-27M |
| IP Strategy | 0.5-1M |
| Salary (Scaling to 30-40 employees) | 28-37M |
| Consumables | 4-4.5M |
| Rent and Utilities | 5-8M |
| Regulatory approvals | 5-9M |
| Clinical Phase III | 90-100M |
| Marketing and Partnerships | 19M |
In the early stage, the focus is on laboratory setup, proof-of-concept experiments, and initial IP protection. Funding sources here are typically public grants, academic incubator programs, and early angel/accelerator funding. European Union programs such as Horizon Europe provide competitive funding opportunities for high-risk, high-gain projects in biotechnology. iGEM itself also offers follow-up opportunities through iGEM EPIC and industry accelerators, which bridge student projects into startups (iGEM Foundation, 2023).
At this stage, siREN would transition from preclinical validation to early human trials. The funding requirements expand to tens of millions of euros. Financing sources here are typically venture capital (VC) rounds, strategic pharma partnerships, and disease-focused foundations. In Europe, life sciences venture capital investments reached €9.4 billion in 2021, demonstrating strong investor appetite for RNA and oncology startups.
Pharmaceutical partnerships are particularly important: licensing or co-development deals allow large pharma companies to de-risk their pipeline by collaborating with startups at the preclinical or Phase I/II stage. Orphan drug designation also improves funding opportunities by offering tax credits, fee reductions, and extended market exclusivity, which are attractive for investors and partners.
The most expensive stage is Phase III trials, which can cost upwards of €90–100 million. At this point, siREN would rely heavily on large-scale pharmaceutical partnerships, licensing agreements, or acquisition. Historically, the majority of biotech startups exit through licensing or M&A before Phase III, as large pharmaceutical companies have the infrastructure and capital to conduct global pivotal trials [].
Alternative funding mechanisms include public offerings (IPO or SPACs), which European biotechs increasingly use to fund late-stage clinical development []. Strategic partnerships for manufacturing with contract development and manufacturing organizations (CDMOs) also reduce the capital required to build in-house facilities.
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.
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).
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.
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.
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