Executive Summary / Key Takeaways

• Transformative J&J Partnership: Nanobiotix has fundamentally de-risked its lead asset, NBTXR3, through a global licensing agreement with Johnson & Johnson , potentially valued at over $2.5 billion plus royalties, accelerating its path to market and securing significant future milestones.
• Physics-Based Technological Edge: NBTXR3, a hafnium oxide nanoparticle, uniquely amplifies radiation therapy's anti-tumor activity without increasing toxicity to healthy tissue, demonstrating compelling efficacy signals in head and neck, pancreatic, and melanoma cancers.
• Strengthened Financial Position: Strategic amendments to the J&J agreement and milestone payments have extended Nanobiotix's cash runway into mid-2026, significantly reducing future cash burn and providing a clearer path to financial sustainability.
• Robust Clinical Pipeline & Near-Term Catalysts: Multiple data readouts are anticipated in 2025 and 2026 across various solid tumor indications for NBTXR3, including pivotal Phase 3 and randomized Phase 2 studies, offering substantial value inflection points.
• Long-Term Growth Beyond NBTXR3: The company is strategically advancing two additional nanoparticle platforms, Curadigm and Oocuity, aiming to diversify its pipeline and leverage future NBTXR3 revenues to drive sustained innovation and growth.

A New Era for Oncology: Nanobiotix's Physics-Driven Approach

Nanobiotix S.A. (NASDAQ:NBTX), a clinical-stage biotechnology company founded in 2003, is pioneering a novel approach to cancer treatment through its innovative nanoparticle-based therapies. The company's core mission revolves around leveraging nanophysics to develop first-in-class products with broad applicability, aiming to address significant unmet needs in oncology. This strategy is particularly relevant given that approximately 60% of all cancer patients receive radiation therapy, a treatment NBTXR3 is designed to profoundly enhance. The company's journey has been marked by a relentless focus on its lead candidate, NBTXR3, and a recent, transformative partnership with Johnson & Johnson that is reshaping its trajectory.

The oncology landscape is intensely competitive, dominated by large pharmaceutical players such as Merck & Co. , Bristol-Myers Squibb , AstraZeneca , and Pfizer , all with extensive portfolios and global commercial reach. Nanobiotix, as a clinical-stage entity, occupies a specialized niche, differentiating itself through its proprietary physics-based technology. While larger competitors often focus on broad-spectrum immunotherapies or chemotherapy regimens, Nanobiotix's NBTXR3 offers a targeted enhancement of an existing, widely used treatment modality: radiation therapy. This specialized focus allows Nanobiotix to innovate rapidly in its specific area, potentially offering qualitatively superior performance in radiation efficacy for certain cancers. However, its smaller scale and high R&D dependencies mean it faces challenges in financial performance and market penetration compared to its established rivals.

Technological Edge: NBTXR3's Physics-Based Power

At the heart of Nanobiotix's investment thesis lies NBTXR3, also known as JNJ-1900, a potential first-in-class radioenhancer. This innovative therapeutic is a sterile aqueous suspension of crystalline hafnium oxide (HfO2) nanoparticles, approximately 50 nanometers in diameter. HfO2 is a biologically inert, electron-dense material that acts as a potent X-ray absorber and radiation amplifier. The mechanism of action is universal, based on physics rather than tumor or patient biology, making it tumor-agnostic, patient-agnostic, and target-agnostic. NBTXR3 is administered as a one-time intratumoral injection directly into the solid tumor before the first course of radiation treatment. This localized delivery maximizes concentration and efficacy within the tumor while minimizing systemic exposure and toxicity to surrounding healthy tissues.

The tangible benefits of NBTXR3 have been demonstrated across multiple clinical studies. In the pivotal Phase 3 NANORAY-312 study for elderly, frail patients with locally advanced head and neck cancer (ineligible for cisplatin), NBTXR3 has shown promising results. The Phase 1 Study 102, which informed the Phase 3 design, reported a 64% complete response rate and an 82% overall response rate. Critically, patients in Study 102 achieved a median progression-free survival (PFS) of 16.9 months and a median overall survival (OS) of 23.1 months, nearly doubling historical outcomes for this vulnerable population. Exploratory analysis further highlighted a median OS of 42.8 months in the 82% of evaluable patients who showed a response in the NBTXR3-injected lesion, indicating a strong correlation between local response and extended survival.

Beyond head and neck cancer, NBTXR3 has shown encouraging signals in other difficult-to-treat indications. In a Phase 1b study for locally advanced pancreatic cancer conducted with MD Anderson Cancer Center, NBTXR3 combined with radiation therapy demonstrated a preliminary median OS of 23 months, surpassing the 19.2 months observed in historical controls who received an additional course of chemotherapy. Furthermore, 42% of NBTXR3-treated patients achieved normalization of the CA19-9 biomarker, compared to 17% in historical controls. Most recently, new results from the Phase 1 Study 1100 in primary cutaneous melanoma, focusing on patients resistant to anti-PD-1 therapy, showed a favorable safety profile, a 47.4% objective response rate, a 78.9% disease control rate, and a median OS of 14.6 months in a heavily pre-treated population. These results underscore NBTXR3's potential to improve local control and potentially prime the immune system, offering a new therapeutic avenue for patients with limited options.

Strategic Transformation: The Johnson & Johnson Partnership

A pivotal moment in Nanobiotix's history was the summer 2023 signing of a global licensing agreement with Janssen Pharmaceutica, a Johnson & Johnson company. This collaboration, potentially valued at over $2.5 billion plus tiered royalties (low teens to low 20s), is designed to accelerate and broaden the development and commercialization of NBTXR3 worldwide. The partnership initially focuses on head and neck and lung cancers, which alone represent over 100,000 addressable patients in the U.S. and EU5, a market estimated to be worth $10 billion.

A significant strategic move within this partnership was the transfer of global sponsorship for the pivotal Phase 3 NANORAY-312 study in head and neck cancer to Janssen, expected around Q3 2025. This deliberate decision aims to streamline the product's path to market, allowing J&J to be fully prepared for regulatory submissions and commercialization without delays post-results. This amendment to the global licensing agreement also substantially reduced Nanobiotix's funding obligations for NANORAY-312, releasing J&J from select future potential milestone payments while safeguarding Nanobiotix's path to sustainable cash flow through hundreds of millions in potential milestone payments. J&J has also begun replicating Nanobiotix's manufacturing process to ensure increased product availability, further demonstrating their commitment.

The collaboration extends beyond head and neck cancer. In January 2025, J&J initiated the CONVERGE randomized Phase 2 study in unresectable Stage III non-small cell lung cancer, a significant expansion of NBTXR3's clinical pipeline. This strategic alignment with a global pharmaceutical leader like J&J provides Nanobiotix with the resources, expertise, and global reach necessary to maximize NBTXR3's potential, a capability that would be challenging for a clinical-stage biotech to achieve independently. This partnership effectively de-risks the commercialization pathway and validates the platform's scientific approach.

Financial Performance and Liquidity: A De-Risked Horizon

Nanobiotix's financial performance in 2024 reflected the strategic shifts initiated by the J&J partnership. The company reported negative revenue of €7.2 million in 2024, a notable decrease from €36.2 million in 2023. This negative figure was primarily a non-cash accounting impact of €19.3 million, resulting from the transfer of NANORAY-312 study sponsorship to Janssen, which necessitated the recognition of a net liability. This was partially offset by €5.9 million from sales of clinical products, €1.8 million from technology transfer services to Janssen, and €3.3 million in research tax credits. The significant revenue in 2023 was largely driven by the initial execution of the Janssen license agreement and a NANORAY-312 development milestone.

Research and Development (R&D) expenses increased by 5% to €40.5 million in 2024 from €38.4 million in 2023, primarily due to heightened clinical development activities for NANORAY-312 and Study 1100, alongside the full-year impact of R&D personnel recruited in 2023. Conversely, Selling, General, and Administrative (SG&A) expenses decreased by 7% to €20.5 million in 2024 from €22 million in 2023, mainly due to one-off fees incurred in 2023 related to the license agreement and equity issuance. The net loss attributable to shareholders widened to €68.1 million (€1.44 per share) in 2024, up 72% from €39.7 million (€1.08 per share) in 2023, predominantly due to the aforementioned non-cash negative revenue recognition.

As of December 31, 2024, Nanobiotix held €49.7 million in cash and cash equivalents, a decrease from €75.3 million at the end of 2023. However, the strategic amendment to the J&J agreement, which removed the vast majority of Nanobiotix's funding obligation for NANORAY-312, has significantly bolstered the company's liquidity outlook. This change, coupled with anticipated milestone payments, is projected to fund operations into mid-2026. Management is actively exploring further non-dilutive financing options to extend cash visibility into 2027. The company expects over $200 million in medium-term milestones within the next two to three years, which is anticipated to lead to a sustainably financed company.

The removal of the substantial Phase 3 trial costs is expected to result in a meaningful reduction in the operational cash burn beyond mid-2026. This financial de-risking addresses a prior concern for investors and provides a more stable foundation for future development.

Expanding the Horizon: Curadigm and Oocuity

Beyond NBTXR3, Nanobiotix is strategically developing two additional nanoparticle-based platforms, Curadigm and Oocuity, to foster long-term growth and diversify its pipeline. Curadigm, a fully owned next-generation nanotherapeutic platform, is designed to reshape drug delivery. Its lead product, a "nanoprimer," temporarily occupies liver cells responsible for therapeutic clearance. This allows subsequently administered therapeutics to bypass the liver, increasing their systemic bioavailability and accumulation in targeted tissues. This innovative approach has the potential to enhance the efficacy, decrease the toxicity, or reduce the required dose of existing products, and could also enable the creation of entirely new therapies with unique competitive positioning. Nanobiotix views Curadigm as an ideal candidate for multiple partnerships and is actively engaging with the biotech and pharma industry. Updates on Curadigm's strategy and business model are expected by the end of 2025.

The Oocuity platform, while less advanced and not the current primary focus, explores the interaction of nanoparticle materials with neuronal networks. It aims to modulate malfunctioning neuronal networks, potentially reducing neuronal hyperexcitability associated with neuropathic pain, an effect observed in in vitro and mouse models. These platforms represent Nanobiotix's commitment to expanding its leadership in nanoparticle-based therapies, with the expected sustainable revenue from the NBTXR3 collaboration intended to fund their future advancement.

Competitive Landscape and Outlook

Nanobiotix operates in a highly competitive oncology market. While larger players like Merck & Co. (MRK), Bristol-Myers Squibb (BMY), AstraZeneca (AZN), and Pfizer (PFE) possess vast resources, broad product portfolios, and established commercial infrastructures, Nanobiotix differentiates itself through its proprietary NBTXR3 technology. This physics-based approach offers a unique mechanism to enhance radiation therapy, potentially providing a specialized edge in improving local tumor control and systemic immune responses. The strategic partnership with J&J is crucial in bridging the gap in commercialization and global development capabilities, leveraging J&J's scale against the broader market presence of its rivals.

The company's competitive advantages lie in its innovative technology, which has demonstrated compelling clinical data, and its strategic alliances. However, its smaller scale, high R&D expenditures, and reliance on partnerships for commercialization remain vulnerabilities. Barriers to entry in the biotech sector, such as high R&D costs and stringent regulatory requirements, both protect Nanobiotix's niche and limit its ability to expand rapidly against larger, more financially robust competitors.

The outlook for Nanobiotix is marked by several significant catalysts. For NANORAY-312, the transfer of sponsorship to J&J is expected around Q3 2025, with the end of recruitment anticipated in H1 2026. The interim efficacy analysis is also expected in H1 2026, after recruitment completion, with positive results potentially enabling accelerated approval. J&J's CONVERGE study in lung cancer, initiated in January 2025, is expected to yield data in the "not-too-distant future." Further clinical data readouts are anticipated by the end of 2025 for Study 1100 (head and neck recurrent/metastatic, melanoma), pancreatic cancer (full Phase 1 results before summer 2025, with a new cohort recruiting), and esophageal cancer. These milestones, coupled with the expected $200 million-plus in medium-term milestones from J&J over the next two to three years, are critical for Nanobiotix's financial and clinical progression. While the company has de-risked many "big impactful risks," the inherent uncertainties of clinical development mean there is "never 100% guarantee."

Conclusion

Nanobiotix stands at a pivotal juncture, having strategically transformed its outlook through a comprehensive partnership with Johnson & Johnson (JNJ). The core investment thesis centers on NBTXR3's disruptive potential as a physics-based radioenhancer, offering a unique and effective approach to amplify radiation therapy across a broad spectrum of solid tumors. The J&J collaboration not only validates this innovative technology but also provides the necessary resources and global infrastructure to accelerate its development and commercialization, significantly de-risking the pathway to market.

With a strengthened financial position, a robust clinical pipeline poised for multiple near-term data readouts, and the strategic development of next-generation nanoparticle platforms like Curadigm, Nanobiotix is charting a course toward long-term sustainability and growth. The company's ability to execute on its clinical milestones, particularly the NANORAY-312 interim analysis and the CONVERGE study, will be paramount in realizing the substantial value embedded in its lead asset and establishing its competitive leadership in physics-based nanotherapeutics.