On March 17, 2025 NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-stage clinical biotechnology company pioneering disruptive nanotherapeutic approaches to revolutionize treatment outcomes for millions of patients, reported the execution of another disciplined step in its financial strategy through the amendment of the Company’s global licensing agreement with Janssen Pharmaceutica NV, a Johnson & Johnson company (Press release, Nanobiotix, MAR 17, 2025, View Source [SID1234651183]).

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The amendment removes Nanobiotix’s funding obligation for NANORAY-312 and releases Johnson & Johnson from select future potential milestone payments, while safeguarding Nanobiotix’s path to sustainable cashflow through significant potential milestone payments.

Core Components of the Amendment

Johnson & Johnson to Cover NANORAY-312 Costs Through Completion:
Johnson & Johnson will assume nearly all remaining costs for the ongoing pivotal Phase 3 trial through completion, less a small portion of costs that will remain covered by Nanobiotix.
Overall Deal Value Adjusted from Approximately $2.7B to Approximately $2.6B:
Revisions to potential future milestone payments in the amendment total $105M while maintaining first significant milestones and hundreds of millions in potential milestone payments related to the clinical programs for cisplatin-ineligible head and neck cancer and stage 3 unresectable non-small cell lung cancer expected by Nanobiotix in the coming years.
The global licensing agreement, now valued up to approximately $2.6B, includes Nanobiotix eligibility for potential success-based payments that include:
$1.77B, in the aggregate, in potential development, regulatory, and sales milestones related to the first programs including cisplatin-ineligible head and neck cancer and unresectable stage 3 non-small cell lung cancer.
$650M, in the aggregate, in potential additional development, regulatory, and sales milestones related to five new indications that may be developed by Johnson & Johnson at its sole discretion.
$165M, in the aggregate, in potential development, regulatory, and sales milestones for China, South Korea, Singapore, and Thailand.
In addition to the approximately $2.6B in potential milestones outlined above, Nanobiotix remains eligible for $220M in potential development and regulatory milestones per new indication that may be developed by Nanobiotix, in alignment with Johnson & Johnson.
Tiered double-digit potential royalties in the low 10s to low 20s remain unchanged.
Meaningful Extension of Cash Runway and Reduction of Cash Burn:
The amended agreement has enabled Nanobiotix to strengthen its financial position, extending cash visibility to mid-2026, while continuing to explore additional financing options—preferably non-dilutive—to further extend runway into 2027.
Nanobiotix also expects a meaningful reduction of operational cash burn going forward, as the ongoing Phase 3 study previously represented a significant portion of the Company’s operating costs.
"Our disciplined financial approach has provided an important step and continues our positive trend toward long-term stability and profitability," said Bart Van Rhijn, Nanobiotix Chief Financial and Business Officer. "The revised licensing terms with Johnson & Johnson ensure operational alignment given changes in NANORAY-312 responsibilities while preserving key milestone opportunities and extending Nanobiotix cash visibility into mid-2026. We are pleased by what we view as a favorable cost of capital resulting from this amendment. We are continuing to evaluate additional, preferably non-dilutive, financial solutions to further extend runway into 2027 and ensure our path to sustainable revenue through the hundreds of millions in potential milestone payments related to our lead programs expected in the coming years."

Conference Call and Webcast

Nanobiotix will host a conference call and live audio webcast on Tuesday, March 18, 2025, at 8:30 AM EDT / 1:30 PM CET, prior to the open of the U.S. market. During the call, Laurent Levy, chief executive officer, and Bart Van Rhijn, chief financial and business officer, will briefly review the amendment and its impact on the Company before taking questions from participants.

Registration and conference call link: click here

Details of the call are also available in the investors section of the Company’s website at www.nanobiotix.com. It is recommended to join 10 minutes prior the event start. A replay of the webcast will be available shortly after the conclusion of the call and will be archived on the Company’s website.

Participants are invited to email their questions in advance to [email protected].

About JNJ-1900 (NBTXR3)

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. Its proof-of-concept was achieved in soft tissue sarcomas for which the product received a European CE mark in 2019. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

Radiotherapy-activated NBTXR3 is being evaluated across multiple solid tumor indications as a single agent or in combination with anti-PD-1 immune checkpoint inhibitors, including in NANORAY-312—a global, randomized Phase 3 study in locally advanced head and neck squamous cell cancers. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the Phase 3 study.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a collaboration strategy to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several Phase 1 and Phase 2 studies evaluating NBTXR3 across tumor types and therapeutic combinations. In 2023, Nanobiotix announced a license agreement for the global co-development and commercialization of NBTXR3 with Janssen Pharmaceutica NV, a Johnson & Johnson company.

On March 17, 2025 Egle Therapeutics, a clinical-stage biotechnology company developing therapies targeting regulatory T cells (Tregs) for immuno-oncology and autoimmune diseases, reported that it has secured €9.3 million in state funding under the "Innovations in Biotherapies and Bioproduction" call for projects from the France 2030 plan, managed on behalf of the French government by Bpifrance (Press release, Egle Therapeutics, MAR 17, 2025, View Source [SID1234651202]).

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Founded in 2020 as a spin-off from Institut Curie, Egle Therapeutics is a clinical-stage biotechnology company specializing in immunomodulation, with the ambition to develop novel approaches to the modulation of Treg activity for the treatment of cancer and autoimmune diseases.

Egle Therapeutics has developed a proprietary translational platform to identify novel tumor-infiltrating Treg targets, with the aim of developing antibody-based candidate drugs to disable Treg function and restore an effective antitumor immune response.

In June 2020, Egle Therapeutics entered a strategic partnership with Takeda Pharmaceuticals, establishing a three-year research collaboration with an option agreement. Since its inception, the company has successfully raised nearly €56 million through equity financing and non-dilutive public funding, including the i-Lab Innovation Competition and DeepTech Development Grant.

During its Series A financing round in October 2021, the company raised €47 million, attracting renowned investors, including EQT Life Sciences, Bpifrance (INNOBIO 2 and Innovation 1), Fund Plus, Bioqube Factory Fund, T1D Fund, and Takeda Ventures.

In 2024, Egle Therapeutics achieved key milestones, including the launch of its Phase I/II clinical trial for EGL-001, the appointment of Michel Detheux as Chairman, and the appointment of Christophe Quéva as Chief Executive Officer.

"We are honored to receive this funding from the French government through France 2030. This recognition and immense support will help Egle Therapeutics advance its research and development programs in regulatory T cell modulation. The funding granted under the ‘Innovations in Biotherapies and Bioproduction’ call for projects will enable us to accelerate the development of EGL-001, our lead immuno-oncology therapeutic candidate. EGL-001 is currently being evaluated in a Phase I/II clinical trial in France and Spain."

On March 17, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to bexobrutideg (NX-5948) for the treatment of Waldenström macroglobulinemia (WM) (Press release, Nurix Therapeutics, MAR 17, 2025, View Source [SID1234651184]). Bexobrutideg is an orally bioavailable, brain penetrant degrader of BTK which is being evaluated in an ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies.

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The FDA’s Orphan Drug Designation program provides orphan status to therapies intended for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the United States. This designation provides certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved.

"The FDA’s Orphan Drug Designation for bexobrutideg, also known as NX-5948, represents an important milestone in our regulatory strategy and underscores the significant unmet medical need for improved treatments for Waldenström macroglobulinemia," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "Granting of the designation highlights bexobrutideg’s potential to provide patients with WM a promising new therapeutic option. We are also pleased to announce that our investigational therapy bexobrutideg has been assigned a nonproprietary name reflecting its novel mechanism of action, designated with the unique suffix "deg" for degrader."

In collaboration with the national naming authority, United States Adopted Name (USAN) Council, Nurix’s lead BTK degrader, NX-5948, was assigned the nonproprietary name "bexobrutideg." The U.S. and international drug naming convention is designed to select a single name of worldwide acceptability for each active substance that is intended to be marketed as a pharmaceutical. Most notable with bexobrutideg is the designation of a new suffix, "deg," which references bexobrutideg’s novel degradation mode of action. Targeted protein degraders are characterized by their bifunctional nature, binding to both a target protein and a ligase to drive ubiquitination and catalytic degradation of the target through the proteasome. The new deg suffix is an important recognition that the mechanism of action, pharmacokinetics and pharmacodynamics of targeted protein degraders are fundamentally different than inhibitors, which all use the "ib" suffix. The central stem of the name, "bruti," references the target, Bruton’s tyrosine kinase (as used in ibrutinib, zanubrutinib and acalabrutinib). The prefix "bexo" is the unique identifier of a specific agent in the class and is often used for ease of reference to the agent.

"We are excited that bexobrutideg has been recognized by the USAN Council as a unique entity and member of a new class of small molecule drugs, targeted protein degraders," said Gwenn Hansen, Ph.D., chief scientific officer of Nurix. "The catalytic mechanism of action and event driven pharmacology triggering ubiquitination and proteasomal degradation of a target protein is highly differentiated from inhibitors and allows degraders to eliminate the totality of a protein’s function. In our BTK degrader clinical program, we have also established that degraders can eliminate mutant oncoproteins that have proven to be resistant to inhibitor therapy."

About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK that is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix has previously reported encouraging safety and efficacy data in patients with WM treated in the ongoing Phase 1a/b clinical trial of bexobrutideg demonstrating early promise of clinical benefit with potential for durable outcomes. Nurix continues to enroll patients with WM in an ongoing Phase 1b expansion cohort and anticipates sharing additional clinical data in 2025. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022). Nurix is also developing bexobrutideg for the potential treatment of inflammatory diseases.

About Waldenström Macroglobulinemia (WM)
WM is a rare, slow growing type of non-Hodgkin’s lymphoma that is characterized by the replacement of normal bone marrow cells by malignant lymphocytic cells that produce monoclonal IgM. This replacement leads to anemia, bleeding, and impaired immune function, while the elevated IgM levels may cause neurologic symptoms. The incidence of Waldenström macroglobulinemia ranges from 0.361,2 to 0.573 per 100,000 people in the United States or approximately 1,200 to 1,900 annually. With a median disease duration approaching 10 years, 4 approximately 12,000 to 19,000 patients are living with Waldenstrom’s macroglobulinemia in the United States. Recommended first-line treatments including chemoimmunotherapy and BTK inhibitor (BTKi) therapy. There are no therapies approved to treat WM patients after a BTKi.

On March 17, 2025 CEL-SCI Corporation (NYSE American: CVM) reported it received comments from the U.S. Food and Drug Administration (FDA) on the confirmatory Registration Study’s Statistical Analysis Plan (SAP) submitted in December of 2024 for the study of Multikine* (Leukocyte Interleukin, Injection) as a neoadjuvant in the treatment of newly diagnosed previously untreated locally advanced head and neck cancer (Press release, Cel-Sci, MAR 17, 2025, https://www.businesswire.com/news/home/20250316883464/en/CEL-SCIs-Head-and-Neck-Cancer-Registration-Study-Protocol-Clears-FDA-Reviewin-Talks-with-Potential-Partners-Interested-in-Commercialization-of-Multikine [SID1234651203]). The FDA stated no response to their comments were required from CEL-SCI and that the agency presently has no comments on the confirmatory study protocol, which was submitted for FDA review contemporaneously with the SAP in December 2024.

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CEL-SCI’s 73,000 square foot Multikine manufacturing facility presently has the capacity to produce over 12,000 Multikine treatments per year. Over $200 million has been invested in the facility and the development and validation of its proprietary biologic manufacturing processes.

"Given Multikine’s excellent survival data, strong statistics and the recent focus on PD-L1 as a diagnostic biomarker for predicting the most effective treatment strategy for head and neck cancer, we are pursuing discussions with key parties to help CEL-SCI complete the last study needed in order to pursue marketing approval for Multikine," stated CEL-SCI CEO Geert Kersten.

"These discussions may lead to potential partnerships involving non-dilutive funding for the 212-patient confirmatory Registration Study designed to bring Multikine to market. We are seeing new interest from highly placed individuals and commercial entities that recognize that Multikine, based on its different mechanism of action, is uniquely positioned to treat about 70% of head and neck cancer patients who have low PD-L1 tumor expression, an area where commercially available PD-L1 inhibitors such as nivolumab and pembrolizumab cannot help. These data, combined with our dedicated Multikine manufacturing facility, position Multikine as a very attractive oncology asset," Kersten concluded.

CEL-SCI completed a randomized controlled Phase 3 study conducted in 928 locally advanced, resectable head and neck cancer stage 3 and 4a patients in 23 countries on 3 continents. The Phase 3 study demonstrated strong statistical results and improved survival with Multikine neoadjuvant treatment over control. The 5-year survival rate of the target patient population that will be treated in the confirmatory Registration Study increased to 73% when patients were treated with Multikine before standard of care vs 45% for control patients who received only the standard of care treatments. The survival advantage over control was accentuated in patients who had low to zero expression of PD-L1 on their tumors and had lower disease burden by having N0 (no nodal involvement).

On March 17, 2025 Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, reported positive results from the pivotal Phase 3 Precision-T study of Orca-T, its lead investigational allogeneic T-cell immunotherapy, in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL) (Press release, Orca Bio, MAR 17, 2025, https://orcabio.com/orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies/?utm_source=rss&utm_medium=rss&utm_campaign=orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies [SID1234651185]). Orca-T is manufactured using highly purified regulatory T-cells, hematopoietic stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors.

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In the randomized Precision-T study, Orca-T met the primary endpoint of a statistically significant improvement in survival free of moderate-to-severe chronic graft versus host disease (cGvHD) with Orca-T. At one year, the rate for patients who received Orca-T was 78% compared to 38% for patients who received a conventional allogeneic hematopoietic stem cell transplant (alloHSCT). Patients in the Orca-T group achieved an estimated overall survival (OS) of 94% compared to 83% in the alloHSCT arm at one year.

"Today, treating patients with serious blood cancers using allogeneic stem cell transplants requires a difficult risk-benefit trade-off as clinicians aim to cure the disease while avoiding potentially deadly treatment-related toxicities, like GvHD," said presenting author Everett Meyer, M.D., Ph.D., hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care. "The Precision-T study showed double the rate of survival free from GvHD with Orca-T versus a conventional transplant, a relapse-free survival rate of 76% and no new safety concerns. These findings are highly encouraging and provide compelling new evidence as we work to solve for the critical factors contributing to the needs of this patient population."

Precision-T Study Results

In the study, all patients (n=187) with a median age of 43.5 years (range 19-65 years) were randomized 1:1 to Orca-T plus single-agent tacrolimus (TAC) or alloHSCT plus TAC methotrexate (TAC/MTX). Patients across both groups received myeloablative conditioning (MAC) and used a related or unrelated matched donor. Patients had a median follow-up time of 11.4 months (range 0.2-24.3 months) across both arms. Key results from the Precision-T study at one year are summarized below:

The primary endpoint of survival free of cGvHD was 78% (95% CI: 65%, 87%) in the Orca-T arm (n=93) and 38% (95% CI: 26%, 51%) in the alloHSCT arm (n=94) (HR 0.26; p<0.00001).
An interim analysis of the secondary endpoint of OS was 94% (95% CI: 86%, 97%) in the Orca-T arm and 83% (95% CI: 73%, 90%) in the alloHSCT arm (HR 0.49; p=0.11823).
An additional secondary endpoint of cumulative incidence of moderate-to-severe cGvHD was 13% (95% CI: 5%, 23%) and 44% (95% CI: 31%, 56%) in the Orca-T and alloHSCT arms, respectively (HR 0.19; p<0.00002).

Exploratory endpoints at one year include the rate of relapse-free survival which was 76% and 74% in the Orca-T and alloHSCT arms, respectively (HR 0.80, p=0.49). The cumulative incidence of non-relapse mortality was 3% in the Orca-T arm and 13% in the alloHSCT arm. Additionally, the cumulative incidence of Grade 3 or 4 acute GvHD was 6% and 17% in the Orca-T and alloHSCT arms, respectively.

No new safety issues were identified with Orca-T. Grade ≥ 4 infections per CTCAE scoring were noted in 6% and 10% of patients in the Orca-T and alloHSCT arms, respectively.

Orca-T was manufactured in Orca Bio’s centralized GMP facility and delivered to patients at 19 treatment centers across the U.S., with all infusions occurring within a vein-to-vein time of 72 hours or less.

"Approximately 46,000 people are diagnosed with AML, ALL and MDS in the U.S. each year, but only a fraction of them receive an allogeneic stem cell transplant within the current paradigm," said Rawan Faramand, M.D., Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center. "Additional treatment options are needed, and the introduction of a cell therapy like Orca-T that leverages a precision-based approach could pave the way for a new standard of care for patients with various hematologic malignancies."

"These exciting results underscore Orca Bio’s vision of transforming the treatment landscape for patients living with serious blood cancers, potentially standardizing curative treatment for diseases like AML, ALL and MDS," said Ivan Dimov, Ph.D., co-founder and chief executive officer at Orca Bio. "We are working closely with the FDA and expect to submit a Biologics License Application this year. These results support the validity of our high-precision platform as we continue to advance our robust pipeline of allogeneic cell therapies for the treatment of hematologic malignancies, autoimmune diseases and beyond."

Orca Bio is grateful to the patients and families, donors and trial site investigators who participated in the Precision-T study.

The complete results will be presented on April 2, 2025, at the 51st Annual Meeting of The EBMT in Florence, Italy.

About Precision-T
Precision-T (NCT05316701) is a randomized, open-label multi-center study that evaluated the safety, efficacy and tolerability of Orca Bio’s lead investigational allogeneic T-cell immunotherapy, Orca-T, compared to conventional allogeneic hematopoietic stem cell transplant (alloHSCT). Orca Bio received guidance from the U.S. Food and Drug Administration on the design of Precision-T, which evaluated Orca-T in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). There are 19 leading treatment centers participating in the trial, which enrolled 187 patients across the U.S.