Entrepreneurship

Mission Statement

Problem Focus

Cancer remains one of the greatest challenges facing modern medicine, responsible for millions of deaths each year worldwide - a number projected to keep rising. Despite being a collection of diverse diseases, all cancers share a core mechanism: genetic mutations that cause cells to behave abnormally and aggressively. The close similarity between cancerous and healthy cells makes effective treatment particularly difficult. Conventional therapies such as chemotherapy and radiation often damage healthy tissue, resulting in severe side effects and limited long-term success. Moreover, these approaches may fail to eliminate all cancer cells, leading to recurrence. In recent years, oncology has begun to embrace precision medicine - targeted therapies that aim to treat each patient according to their specific genetic and molecular profile. However, current options still lack the specificity and flexibility needed to overcome many of cancer’s complexities. There is a critical need for innovative treatments that can silence cancer-driving genes in a programmable and efficient manner - a need our project aims to fulfill through antisense oligonucleotide (ASO) therapy. This need is especially pressing in lung cancer, one of the deadliest cancers worldwide, where current therapies often prove insufficient. making it an ideal starting point for our solution.

Core Solution

ONCOLIGO is a tri-functional therapeutic platform centered on an antisense oligonucleotide (ASO) designed to silence cancer-driving RNA. The ASO is optimized by a proprietary computational model that analyzes RNA structure, hybridization energy, accessibility, and off-target potential to generate highly specific and effective sequences.
The ASO targets synthetic lethal partners of tumor suppressor genes, selectively killing tumor cells while sparing healthy tissue. To ensure safety, the ASO is paired with the BROTHERS system - a molecular safety switch that activates the ASO only upon recognition of the correct RNA target via toehold-mediated strand displacement.
The therapeutic construct is delivered directly to cancer cells using monoclonal antibodies that recognize tumor-specific surface markers. Once inside the cell, attached peptide epitopes - derived from tumors or pathogens - promote antigen presentation and stimulate cytotoxic T cell responses.

Target Beneficiary

We aim to serve cancer patients for whom current treatments are ineffective, particularly those with rare, resistant, or relapsing tumor types that lack targeted therapeutic options.
Our initial efforts are focused on lung cancer, a major cause of cancer-related deaths worldwide, as a proof-of-concept for our platform’s clinical potential. At the same time, our long-term goal is to adapt and expand this approach to other types of cancer through mutation-specific design.
We also aim to deliver a powerful precision platform that enables clinicians and researchers to advance targeted gene silencing and personalized therapy development.

Differentiator / Value

ONCOLIGO outperforms traditional RNA therapies by integrating precision, safety, immune activation, and targeted delivery into a single modular platform.
At its core is a programmable antisense oligonucleotide (ASO), optimized by a proprietary computational model to maximize efficacy and minimize off-target effects. By targeting synthetic lethal partners of tumor suppressor genes, ONCOLIGO reaches cancers previously considered "undruggable," enabling highly selective tumor cell killing.
The BROTHERS system adds an extra layer of safety by activating the ASO only in the presence of the correct RNA target. Tumor- or/and pathogen-derived peptide epitopes enhance immune recognition, while monoclonal antibodies ensure precise delivery to cancer cells.
Together, these innovations make ONCOLIGO a next-generation solution for safe, adaptable, and personalized cancer therapy.

Impact Goal

Our mission is to transform cancer therapy by creating a new class of treatments that are safe, mutation-specific, and clinically adaptable. While our current development is centered on lung cancer as a starting point, our modular design enables rapid expansion to additional cancer types, ultimately offering a versatile and impactful tool for the future of precision oncology.

Unmet Need in Lung Cancer Treatment

Lung cancer remains one of the most challenging and deadly forms of cancer, with many patients still lacking effective, long-term treatment options. In this section, we outline the urgent unmet need by highlighting three key aspects: the global burden and rising incidence of the disease, the critical limitations of current treatment modalities, and the firsthand experiences of both clinicians and patients confronting these gaps in care.

Disease Burden

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. According to the American Cancer Society 2025 report, lung cancer is responsible for approximately 1 in 5 cancer deaths, with an estimated 226,650 new cases and 124,730 deaths (Lung & bronchus cancer) expected in the United States alone this year [1]. Globally, according to GLOBOCAN 2022, lung cancer was the most commonly diagnosed cancer, accounting for nearly 2.5 million new cases (12.4% of all cancers), and the leading cause of cancer death, responsible for 18.7% of global cancer-related mortality. The burden is particularly high among men, though incidence among women is rising, with substantial geographic variation observed across continents [2].

The World Health Organization (WHO) attributes the rising burden of lung cancer, particularly in regions such as Asia, to increasing tobacco consumption [3].

Despite advances in targeted therapies and immunotherapies, the five-year survival rate for lung cancer remains below 30%, largely due to late-stage diagnosis and limited treatment options for patients with rare or less-studied mutations [1].

According to GLOBOCAN 2022, the number of new cancer cases worldwide is expected to reach over 35 million by 2050, marking a 77% increase compared to approximately 20 million cases reported in 2022. This projected rise is largely attributed to population growth and ageing, occurring alongside a global demographic shift toward lower birth and death rates. In parallel, the International Agency for Research on Cancer (IARC) anticipates a significant rise in lung cancer, with incidence projected to grow by 58.8% and mortality by 64% between 2020 and 2040 [2].

The development of lung cancer is strongly associated with environmental and behavioral risk factors. Smoking remains the predominant cause, contributing to approximately 85–90% of all cases. However, other exposures, such as second-hand smoke, family history, and contact with carcinogenic substances are also significant contributors. Additionally, underlying medical conditions like pulmonary fibrosis, HIV infection, and lifestyle factors such as alcohol use further increase the likelihood of developing the disease [3].

Despite advances in surgery, radiation, chemotherapy, and immunotherapy, non-small cell lung cancer (NSCLC) remains a major clinical challenge, particularly due to the high rates of recurrence and metastasis after treatment. NSCLC accounts for approximately 85% of all lung cancer cases, with three main types - adenocarcinoma (40%), squamous cell carcinoma (25–30%), and large cell carcinoma (5–10%). However, many patients who undergo curative-intent surgery still experience distant metastases or local recurrence, highlighting the limitations of current therapeutic strategies and the urgent need for novel approaches [3].

NSCLC is often diagnosed at an advanced stage, limiting treatment options. The most common symptom is cough (50–75% of cases), but its nonspecific nature contributes to delayed detection. Despite the use of PET-CT and liquid biopsy, accurate diagnosis still requires tissue sampling [3].

Metastatic non-small cell lung cancer (mNSCLC) imposes a substantial economic burden on the U.S. healthcare system, particularly during the period between diagnosis and the initiation of first-line treatment. A 2023 ISPOR study revealed that for patients with commercial insurance, average per-patient-per-month (PPPM) costs during this early phase reached $64,253, driven primarily by medical services ($61,824) and pharmacy-related expenses ($2,429). Even for patients with public insurance (Medicaid), PPPM costs exceeded $34,000. These costs decline in subsequent phases, but remain significant. Notably, patients with mNSCLC without actionable EGFR or ALK mutations, who make up the majority, face limited treatment options despite repeated healthcare utilization and high failure rates of existing first-line therapies. This gap highlights both a clinical and financial need for a new biologic therapy that accelerates therapeutic efficacy or delays progression. Such an intervention could reduce resource-intensive care periods and hospitalization rates, lowering payer expenditures while improving patient outcomes [4].

Our project focuses on developing an antisense oligonucleotide (ASO) based therapy tailored to a genetically defined subpopulation of lung cancer patients. To ensure both clinical relevance and scalability, we aim to target a mutation (or set of mutations) present in at least 5% of lung cancer patients. This precision approach will allow us to address a biologically significant subset of patients who may not respond well to current treatments.

By identifying such a subgroup and designing molecular therapy, we aim to fill a critical gap in personalized oncology. Our approach is particularly relevant for non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancer cases, and where genetic heterogeneity poses a challenge for effective, long-term treatment.

Current Treatment Limitations

Despite major advances in therapy over the past two decades, significant limitations persist across existing treatment modalities.

Traditional chemotherapy kills rapidly dividing cells indiscriminately, leading to severe side effects and often incomplete tumor eradication [5], the last two decades have seen the rise and consolidation of all major cancer treatment modalities. These include targeted therapies (e.g., EGFR, ALK inhibitors) and biological drugs (e.g., monoclonal antibodies like Nivolumab or Bevacizumab), which act more selectively on cancer-driving molecules [6],[7]. At the same time, traditional treatments such as chemotherapy and radiotherapy remain widely used in clinical practice, although the primary focus of research and innovation has shifted toward more precise and personalized approaches.

These newer therapies offer improved safety and efficacy - but only for a subset of patients with specific genetic mutations or protein biomarkers, and even these advanced therapies have limitations:

1. Restricted to Membrane: Most targeted therapies act on cell-surface proteins. This restricts their utility because intracellular targets, such as mutated proteins, mRNA, or non-coding RNAs, remain largely inaccessible. Antibody development is limited to extracellular targets and is expensive, time-consuming, and often hampered by tumor heterogeneity and antigen loss [8],[9].
2. Mutation-Driven Resistance: Cancer cells are highly dynamic. During treatment, secondary mutations, alternative splicing, or gene amplifications can emerge, rendering once-effective drugs obsolete. This is especially common with EGFR and ALK inhibitors, where resistance often develops within months. As resistance accumulates and toxicities limit further treatment, some patients exhaust all available drug options, leaving their physicians with no additional therapies to offer - a devastating outcome that underscores the need for more versatile and durable treatment strategies [10],[11].
3. Patient Eligibility Is Narrow: Precision oncology often depends on identifying specific mutations or biomarkers in each patient. Even within a single gene, such as EGFR or KRAS, dozens of distinct mutations can exist - each potentially requiring a different therapeutic approach. As a result, most drugs are only effective for a small subset of patients with the "right" mutation, leaving many without an applicable targeted treatment [12].
4. Missed Opportunities: Targeted therapies have largely focused on oncogenic drivers - genes that gain function and can be inhibited. In contrast, tumor suppressor genes such as TP53, RB1, and APC, which are inactivated in many lung cancers, present a major therapeutic gap. Their loss-of-function nature, combined with the diversity of mutations involved, makes it nearly impossible to "repair" them with a single drug. As a result, these critical genes are often ignored in current treatment paradigms.

To better understand the existing landscape, we compiled a comprehensive table of all FDA-approved non-chemotherapy treatments for lung cancer - including targeted therapies, immune checkpoint inhibitors, and angiogenesis inhibitors.

See Table: “Lung Cancer non-chemotherapy Current Approved Therapies”

While modern therapies have improved outcomes for select patient populations, the limitations outlined above reveal substantial gaps in lung cancer treatment - particularly for patients lacking druggable oncogenic drivers or harboring tumor suppressor gene mutations. These challenges highlight the urgent need for novel, versatile approaches that can overcome resistance, broaden patient eligibility, and effectively target the currently “undruggable” vulnerabilities in cancer.

Patient/Clinician Insight

While lung cancer remains the leading cause of cancer-related death worldwide, the personal experiences of patients and clinicians reveal a deeper, more human dimension of this crisis. One defined not only by biology, but by pain, limitations, and unmet therapeutic needs.

During our meeting with Prof. Amir Onn, Chair of the Institute of Pulmonary Oncology at Sheba Medical Center, he shared the story of a young mother he has been treating since 2016. After nine years of battling lung cancer, none of the available treatments are effective anymore. “I have nothing left to give her”, he said. “No drug works anymore”.

This sense of helplessness, echoed by clinicians facing treatment resistance, is deeply connected to the lived experiences of patients. As therapies lose efficacy over time, patients are left struggling not only with physical decline but with the emotional weight of limited options and uncertain futures.

A 25-year-old nurse shared her story after being diagnosed with stage IV non-small cell lung cancer despite having no risk factors. She recalled the emotional toll of chemotherapy [14]:
“I started chemotherapy and fell into a deep depression. One day, in between chemo sessions, I remember sitting in my bed and thinking: "It would be so much easier if I just ended it now and saved everybody the trouble.”

Following initial chemotherapy, she began drug therapy that brought temporary improvement, but she remained aware of its limitations:
“Drug therapy isn't a cure; it’s a treatment. I had to come to terms with that. Eventually, the drugs will become less effective as my body adapts and the cancer finds ways around it.”

Still, she expressed cautious hope for the future:
“The hope is to one day treat this type of lung cancer, or all cancers, like we treat diabetes—as a chronic condition that can be managed.”

These personal accounts are echoed by the study 'Symptoms and experiences of frailty in lung cancer patients with chemotherapy' [14] which explored the experiences of 302 lung cancer patients undergoing chemotherapy. Many reported severe fatigue, appetite loss, anxiety, and social withdrawal.

Further supporting this picture, the study 'Living with advanced or metastatic lung cancer - A qualitative study on the experiences of patients' [15], interviewed 19 patients with advanced or metastatic NSCLC. Participants described how symptoms like shortness of breath, persistent cough, and fatigue interfered with walking, sleeping, and daily life. They also reported confusion about whether their symptoms came from the disease or the treatment - adding emotional distress to physical discomfort.

Together, these insights highlight the urgent need for treatments that reduce systemic toxicity, preserve patients’ quality of life, and adapt to the evolving biology of lung cancer. ASO-based therapeutics represent a promising direction toward fulfilling this unmet need.

Solution and Tech

Market Size and Opportunity

Our comprehensive market analysis reveals a significant opportunity in the target sector. The market is experiencing rapid growth due to increasing demand for sustainable solutions and regulatory support for innovative biotechnology applications.

Competitive Landscape

We have conducted thorough competitive analysis, identifying key players and their strengths and weaknesses. Our solution addresses gaps in the current market offerings, providing unique value that differentiates us from competitors.

Customer Segments

Through extensive customer discovery interviews, we have identified primary and secondary customer segments. Our target customers have validated the problem we're solving and expressed strong interest in our proposed solution.

Market Analysis

Minimum Viable Product (MVP)

Our MVP demonstrates the core functionality of our solution while minimizing development costs and time to market. We have successfully prototyped and tested our MVP with potential customers, receiving valuable feedback for iterative improvements.

Product - SWOT Analysis

To evaluate the strategic positioning of Oncoligo, we conducted a comprehensive SWOT analysis. This framework helps us identify the key internal strengths and weaknesses of our ASO-based platform, as well as the external opportunities and threats that shape its development. By understanding these factors, we can better focus our efforts, refine our strategy, and prepare for real-world implementation in the fight against lung cancer.

How We Plan to Overcome Our Weaknesses

How We Plan to Overcome Our Threats

Competitive Landscape & Differentiation

RNA therapeutics are rapidly transforming oncology, with numerous companies developing oligonucleotide approaches[?,?]. Our iGEM project pushes the boundaries by integrating three synergistic strategies:

• Antisense Oligonucleotide (ASO) generated by our unique computational model. designed either to silence synthetic lethality targets or to modulate splicing for neoantigen creation.
• Antibody Conjugation for precise tissue targeting, optimized with multiple computational tools and models.
• Epitope Conjugation to recruit and activate T cell cytotoxicity, derived from smart computational pipeline.

This multi-component, modular combination addresses intracellular mutations and boosts immune-mediated tumor killing - an innovation no competitor currently offers for lung cancer. Below, we analyze the competitive landscape and explain why our approach offers significant advantages.

What Makes Oncoligo Unique?

Feature	Our Platform	Other Players
Modality	ASO + Antibody + Epitope	RNA or Antibody - not both
Modularity and flexibility	Each component can be swapped or redesigned: the ASO sequence can target a new gene, the antibody can be optimized differently and replaced to fit different cancer tissues, and the epitope can be changed and adapted to engage alternative T cell responses.	Non-modular – therapies are fixed designs with little to no flexibility
Target	Intracellular mRNA	Primarily target surface proteins or mRNA for degradation only; none focus on splicing modulation or synthetic lethality partners of tumor suppressor genes.
Mechanism	Synthetic lethality, mRNA knockdown, Splicing modulation and immune system activation.	Protein inhibition or knockdown only
Delivery	Antibody-guided intracellular delivery	Some rely on lipid/viral carriers (less specific), while others have not yet developed clear delivery strategies
Computational Model	Our advanced modeling pipeline predicts RNA accessibility, splicing impact, ASO efficiency, off-target probability, optimal chemical modifications, antibody optimization, epitope conjugation, and many more features. This ensures rational design rather than trial-and-error (See our Model page for details).	Rely on conventional design methods with limited prediction of RNA accessibility or splicing effects. Often depend on empirical screening and trial-and-error, leading to slower optimization and less precise ASO candidates.

Rely on conventional design methods with limited prediction of RNA accessibility or splicing effects. Often depend on empirical screening and trial-and-error, leading to slower optimization and less precise ASO candidates.

We created a table summarizing current leading direct and indirect competitors companies - (See: “Direct & indirect Competitors”), and replacement competitors - (See: “Replacement competitors”).

Direct Competitors - RNA-Based Cancer Therapies

These companies develop therapies that silence gene expression with RNA tools, but do not use antibody or epitope conjugation. Example companies:

In particular, siRNA/shRNA-based therapies, though powerful, have key limitations:

• Depend on RISC complex saturation
• Act only in the cytoplasm
• Are less stable
• Cannot modulate splicing
• Have higher mismatch tolerance, increasing off-target effects [?]
• Are harder to deliver due to their double-stranded nature [?]

In contrast, ASOs:

• Work via RNase H or steric blocking and splicing modular
• Can act in both nucleus and cytoplasm
• Are simpler to synthesize and modify chemically

By leveraging synthetic lethality, our approach can selectively kill cancer cells harboring specific mutations while sparing healthy cells - something no competitor currently implements in lung cancer with ASOs. By targeting the synthetic lethality partner rather than each individual mutation, we gain the major advantage of addressing a wide spectrum of tumor mutations through a single therapeutic strategy (see figure below).

Indirect Competitors - Antibody-Conjugated Therapies

These companies develop antibody-drug conjugates (ADC) or immune engager antibodies. They deliver toxins, proteins, or immune activators, but not RNA. Example companies:

Replacement Competitors - Standard-of-Care Lung Cancer Therapies

Patients today rely on standard-of-care therapies (non-RNA):
Small molecule inhibitors: EGFR, ALK, KRAS G12C (e.g., Sotorasib)
Immunotherapies: Anti-PD-1/PD-L1 (Nivolumab, Pembrolizumab)
Cell therapies: CAR-T

Key gap: Often limited to narrow patient subgroups, develop resistance, and do not target intracellular RNAs.

While these are clinically approved or in development, they primarily:

• Target membrane proteins, leaving intracellular RNAs untargeted
• Are effective only in narrow patient subsets
• Lose efficacy over time due to mutations or pathway redundancy

Future Competitors and Our Strategy to Stay Ahead

We expect future competition from:

• Pharma companies expanding ASO-based therapies for lung cancer, specifically targeting synthetic lethality pathways similar to ours.
• ASO + Antibody combinations, as big pharma and biotech look to integrate RNA payloads into antibody platforms to improve targeting and delivery.
• Epitope-ASO conjugates or new technologies that use ASOs to generate neoantigens, activating the immune system to kill tumor cells with patient-specific T cell responses.

Our strategy to maintain a competitive edge relies on three main pillars:

1. Continuous Innovation Through Modularity

Our modular platform allows rapid swapping or redesign of each component - ASO sequences, antibody carriers, and epitope payloads - without rebuilding the entire system. This agility ensures:

• Fast adaptation to new cancer targets: If competitors develop similar ASOs, we can immediately retarget novel synthetic lethality partners or splice sites.
• Flexible delivery solutions: Antibody or epitope components can be replaced with improved carriers as technology advances.

2. Early Clinical and Partnership Strategy

We plan to:

• Collaborate with pharma companies for delivery optimization, GMP manufacturing, and early-phase clinical trials.
• Engage regulatory agencies early to establish clear translational pathways, securing first-mover advantage in synthetic lethality–based RNA therapeutics for lung cancer.

3. Intellectual Property (IP) Protection

As detailed on our Regulatory & IP Strategy, we patent ASO sequences, epitope constructs, antibody designs, modular platform topology, and computational algorithms. This multi-level patenting ensures that even if competitors develop similar concepts, they cannot replicate our specific sequences, designs, or methods without infringing.

4. Broad Clinical Target Space

Unlike therapies limited to single mutations or pathways, our synthetic lethality approach covers multiple mutations simultaneously. Even if competitors emerge, we can expand rapidly to new cancer subtypes and resistance mechanisms.

Since our platform is multi-component, we created several positioning maps(Figures 1-3). Each one highlights a different dimension of our advantages compared to competitors, showing how Oncoligo outperforms.

This matrix compares leading companies in RNA therapeutics along two key dimensions:

• Resistance Risk (Y-axis): Likelihood of therapeutic resistance development.
• Intracellular Targeting Depth (X-axis): Ability to achieve deep intracellular delivery and targeting.

Oncoligo shows strong performance in Intracellular Targeting Depth with low Resistance Risk, while competitors vary in position across both axes.

This matrix compares companies in RNA therapeutics across two dimensions:

• Modularity (Y-axis): Flexibility of the platform to incorporate multiple therapeutic components.
• Computational Design Capability (X-axis): Integration of computational modeling and design in therapeutic development.

Oncoligo leads with strong Computational Design Capability and Modularity, while competitors show varying strengths across both axes.

This matrix compares companies in RNA therapeutics along two key parameters:

• Functionality (Y-axis): Breadth and versatility of therapeutic mechanisms.
• Delivery Efficacy (X-axis): Efficiency of intracellular delivery and therapeutic performance.

Oncoligo ranks highest in Delivery Efficacy and Functionality, with competitors distributed across both dimensions.

Business Model & Value Proposition

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Development Road-map & Milestones

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Regulatory & IP Strategy

Patent Plan

Our team is developing a comprehensive patent strategy to protect the core innovations of the Oncoligo platform. This strategy spans multiple levels of intellectual property:

1. Sequence

• ASO sequences: Each antisense oligonucleotide we design - whether targeting synthetic lethality pathways in lung cancer or modulating splicing to generate novel neoantigens - can be individually patented as proprietary sequences.
  This ensures exclusivity and protection for our therapeutic pipeline at the molecular level.

2. Epitope

• Novel epitopes: Each tumor-specific or viral-derived epitope identified through our computational pipeline can form the basis of an independent patent.
  These epitopes expand the therapeutic potential of our platform by enabling immune system engagement through new antigen presentation strategies.

3. Antibody Design

• Customized antibodies: We can patent the specific antibody constructs we design, including codon optimization strategies, structural modifications, and the integration of epitopes into the antibody framework.
  This provides IP protection not only for the sequence itself but also for the unique engineering approach that enables targeted delivery and immune activation.

4. Topology

• Modular platform design: We have already filed a patent on the general topology of our system - a modular architecture enabling conjugation of ASOs, antibodies, and epitopes.
  This overarching claim safeguards the platform concept as a whole, allowing flexibility for future iterations.

5. Computational Model & Algorithms

• Design algorithms: Our in-house computational frameworks for ASO design, epitope prediction, and antibody optimization can be patented as methods.

Some components and algorithms in the future may be maintained as proprietary know-how within the company, providing both patent protection and trade-secret leverage.

Together, these elements strengthen our intellectual property position and provide potential licensing and collaboration opportunities in the RNA therapeutics field.

FDA / EMA Pathway

While our project is currently at the preclinical proof-of-concept stage, we have considered the regulatory framework needed to translate our platform into a future clinical application.

Preclinical Requirements: Before advancing to clinical studies, further in vivo experiments will be necessary to evaluate Oncoligo’s efficacy, biodistribution, safety, and toxicity in animal models. These studies are essential to establish pharmacokinetics (PK), pharmacodynamics (PD), and potential off-target effects.

Clinical Trial Phases

Full Development Road-map & Milestones of Oncoligo here

• Phase I: First-in-human studies, primarily focused on safety, tolerability, and dose-escalation in a small group of patients. For oncology, these are often conducted directly in patients with advanced cancers rather than healthy volunteers.
  Phase I would involve patients with advanced or treatment-resistant non-small cell lung cancer (NSCLC) rather than healthy volunteers, since the therapeutic targets cancer-specific vulnerabilities. The primary goal would be:
  • Safety & Tolerability: Assessing potential off-target effects of the ASO platform, including immunogenicity and toxicity.
  • Dose-Escalation: Determining the optimal dose for ASO delivery and conjugation constructs (e.g., antibody-oligonucleotide conjugates).
  • Pharmacokinetics/Biodistribution: Tracking ASO accumulation in tumor vs. healthy tissue using imaging and molecular biomarkers.

A secondary goal may include early biomarkers of response, such as changes in target mRNA expression or tumor shrinkage in responders, to guide Phase II design.

• Phase II: Evaluation of efficacy and preliminary effectiveness in a larger group, alongside continued safety monitoring. Biomarkers and tumor response rates are typically assessed.
  Phase II trials would expand to a larger NSCLC patient population, with the focus shifting toward:
  • Efficacy: Measuring tumor response rates, progression-free survival, and synthetic lethality biomarkers (e.g., PRMT5/MAT2A in MTAP-deleted tumors).
  • Mechanistic Validation: Correlate (a) ASO-induced mRNA knockdown or splicing modulation and (b) AEO-driven CD8⁺ T-cell immunity with clinical outcomes.
  • Refining Delivery: Comparing delivery methods such as lipid nanoparticles vs. antibody-oligonucleotide conjugates for lung-specific targeting.
• Phase III: Large-scale trials comparing Oncoligo to the standard of care, designed to confirm efficacy, monitor adverse reactions, and generate the data required for regulatory approval.
  Phase III would compare Oncoligo’s platform against the current standard of care in multicenter, randomized controlled trials, focusing on:
  • Statistical Validation of Efficacy: Overall survival, progression-free survival, and objective response rates in diverse NSCLC subgroups.
  • Safety Across Populations: Identifying rare or long-term adverse effects of ASO-based therapeutics.
  • Regulatory Data Generation: Producing the robust dataset required for FDA/EMA approval, including quality-of-life measures and real-world effectiveness.
• Phase IV (Post-Marketing Surveillance): Ongoing studies conducted after approval to monitor long-term safety, rare side effects, and broader clinical benefits.
  • Real-World Effectiveness: Tracking outcomes in a broader patient population, including earlier-stage cancers.
  • Rare Adverse Events: Identifying side effects not seen in controlled trials.
  • Expansion to Other Cancers: Leveraging the modular ASO platform for additional indications with minimal redesign.

Given the urgent need for new lung cancer treatments, we plan to pursue expedited approval pathways such as the FDA Fast Track Designation or the EMA PRIME scheme. These programs are designed to accelerate the development and review of therapies targeting serious conditions with high unmet medical needs.

Freedom-to-Operate Summary

We conducted a preliminary Freedom-to-Operate (FTO) assessment to identify any existing patents that might block the development or commercialization of our ASO constructs and delivery methods.

• Target Gene Patents:
  Our focus includes synthetic lethality partners such as RIOK1, PRMT5, and MAT2A. Several antisense oligonucleotide patents filed against these targets have already expired or are approaching expiration. For example:
  • A RIOK1 antisense oligonucleotide patent application (US20210363525A1) has not matured into active enforceable claims, and prior filings on the gene have expired.
  • Similarly, prior ASO patents combining PRMT5 and MTAP in the context of MTAP deletion (e.g., US20180010132A1) are no longer in force. This ensures that the exact ASO sequences we designed - which are novel and distinct from expired disclosures - are patentable and free from blocking claims.
• Cetuximab as Proof-of-Concept:
  For our antibody-mediated delivery proof-of-concept, we leverage cetuximab (Erbitux). The original composition-of-matter patent for cetuximab has long expired, and biosimilars have entered the market. This allows us to use cetuximab as a model without IP restrictions, while reserving patent space for our unique antibody-oligonucleotide-epitope conjugates.

Together, these findings support our ability to move forward without infringing existing patents. The combination of expired patents on our targets, novelty of our ASO sequences, and expired exclusivity on our proof-of-concept antibody provides a strong FTO position. This paves the way for future filings around our proprietary ASOs, modular antibody designs, and epitope integrations, while keeping potential IP barriers to a minimum.

Financial Plan

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Risk & Fixes

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

People & Stakeholders

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Long Term Impacts

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Social Impact

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Beachhead Market

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Customer Interviews

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Existing Solutions & Benchmarks

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

Pitch

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We have formed strategic partnerships with leading organizations in our target market. These partnerships provide access to resources, expertise, and distribution channels critical for our success.

References

[1] R. L. Siegel, T. B. Kratzer, A. N. Giaquinto, H. Sung, and A. Jemal, “Cancer statistics, 2025,” CA Cancer J Clin, vol. 75, no. 1, pp. 10–45, Jan. 2025, doi: 10.3322/caac.21871.
[2] L. E. L. Hendriks et al., “Non-small-cell lung cancer,” Nat Rev Dis Primers, vol. 10, no. 1, p. 71, Sep. 2024, doi: 10.1038/s41572-024-00551-9.
[3] Y. Alduais, H. Zhang, F. Fan, J. Chen, and B. Chen, “Non-small cell lung cancer (NSCLC): A review of risk factors, diagnosis, and treatment,” Medicine, vol. 102, no. 8, p. e32899, Feb. 2023, doi: 10.1097/MD.0000000000032899.
[4] Nichole Tucker, “Cost of Care for mNSCLC Burdens Healthcare System and Patients”, May 9, 2023, https://www.targetedonc.com/view/cost-of-care-for-mnsclc-burdens-healthcare-system-and-patients.
[5] “How chemotherapy works,” CANCER RESEARCH UK. Accessed: Jun. 06, 2025. [Online]. Available: er/treatment/chemotherapy/how-chemotherapy-works
[6] A. C. Tan and D. S. W. Tan, “Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations,” Journal of Clinical Oncology, vol. 40, no. 6, pp. 611–625, Feb. 2022, doi: 10.1200/JCO.21.01626.
[7] “Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version,” NATIONAL CANCER INSTITUTE, Accessed: Jun. 06, 2025. [Online]. Available: https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq
[8] A. Mishra, R. Maiti, P. Mohan, and P. Gupta, “Antigen loss following CAR‐T cell therapy: Mechanisms, implications, and potential solutions,” Eur J Haematol, vol. 112, no. 2, pp. 211–222, Feb. 2024, doi: 10.1111/ejh.14101.
[9] A. Sorolla et al., “Precision medicine by designer interference peptides: applications in oncology and molecular therapeutics,” Oncogene, vol. 39, no. 6, pp. 1167–1184, Feb. 2020, doi: 10.1038/s41388-019-1056-3.
[10] R. Nussinov, C.-J. Tsai, and H. Jang, “Anticancer drug resistance: An update and perspective,” Drug Resistance Updates, vol. 59, p. 100796, Dec. 2021, doi: 10.1016/j.drup.2021.100796.
[11] Nguyen KS, Kobayashi S, Costa DB. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer. 2009 Jul;10(4):281-9. doi: 10.3816/CLC.2009.n.039. PMID: 19632948; PMCID: PMC2758558.
[12] “Targeted Drug Therapy for Non-Small Cell Lung Cancer,” American Cancer Society. Accessed: Jun. 06, 2025. [Online]. Available: https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html
[13] Macaela MacKenzie, “‘I Was Diagnosed With Stage 4 Lung Cancer at 25,’” Glamour. Accessed: Jun. 06, 2025. [Online]. Available: https://www.glamour.com/story/i-was-diagnosed-with-stage-4-lung-cancer-at-25
[14] L. Duan, H. Cui, W. Zhang, and S. Wu, “Symptoms and experiences of frailty in lung cancer patients with chemotherapy: A mixed-method approach,” Front Oncol, vol. 12, Oct. 2022, doi: 10.3389/fonc.2022.1019006.
[15] A. Cardellino et al., “Perspectives of patients with advanced or metastatic non-small cell lung cancer on symptoms, impacts on daily activities, and thresholds for meaningful change: a qualitative research study,” Front Psychol, vol. 14, Sep. 2023, doi: 10.3389/fpsyg.2023.1217793.