On July 7, 2025 NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-stage clinical biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported two important developments that aim to reinforce the global positioning of potential first-in-class radioenhancer JNJ-1900 (NBTXR3), which is licensed by Janssen Pharmaceutica NV, a Johnson & Johnson company (Press release, Nanobiotix, JUL 7, 2025, View Source [SID1234654360]).

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Health authorities in major European countries have agreed to formally reclassify JNJ-1900 (NBTXR3) from a medical device to a drug, completing a process initiated by Johnson & Johnson to harmonize the product candidate’s regulatory status with classifications already in place in the United States and other major markets. The reclassification follows updated insights into the product candidate’s mechanism of action.

In parallel, Nanobiotix has filed a new composition of matter patent for JNJ-1900 (NBTXR3) that aims to reinforce the intellectual property foundation supporting the product candidate.

"These updates reflect our continued commitment to the JNJ-1900 (NBTXR3) program," said Laurent Levy, co-founder and chairman of the executive board at Nanobiotix. "We are pleased with the progress achieved with health authorities and proud to continue advancing this potential first-in-class product candidate toward patients in need."

JNJ-1900 (NBTXR3) is currently the subject of a comprehensive global clinical development program across multiple tumor types and therapeutic combinations, including a pivotal Phase 3 trial in head and neck cancer.

About JNJ-1900 (NBTXR3)

JNJ-1900 (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 through a successful randomized Phase 2/3 study in 2018. The product candidate’s 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 JNJ-1900 (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 JNJ-1900 (NBTXR3) is being evaluated across multiple solid tumor indications as a single agent or combination therapy. The program is led by 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 JNJ-1900 (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 JNJ-1900 (NBTXR3) across tumor types and therapeutic combinations. In 2023, Nanobiotix announced a license agreement for the global co-development and commercialization of JNJ-1900 (NBTXR3) with Janssen Pharmaceutica NV, a Johnson & Johnson company.

On July 7, 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 European Medicines Agency (EMA) has granted Orphan Drug Designation (ODD) to bexobrutideg (NX-5948) for the treatment of lymphoplasmacytic lymphoma (Press release, Nurix Therapeutics, JUL 7, 2025, View Source [SID1234654261]). Bexobrutideg is an orally bioavailable, brain penetrant degrader of Bruton’s tyrosine kinase (BTK) which is being evaluated in an ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies, including lymphoplasmacytic lymphoma, also known as Waldenström macroglobulinemia (WM).

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The EMA’s Orphan Drug Designation program grants orphan status to therapies intended for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 5 in 10,000 people in the European Union. This designation provides several incentives to encourage the development of treatments for rare conditions, including 10 years of market exclusivity in the EU upon approval, access to protocol assistance, eligibility for centralized marketing authorization, and significant reductions in regulatory fees.

"The EMA’s Orphan Drug Designation for bexobrutideg 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."

Waldenström macroglobulinemia is a rare type of blood cancer that affects B lymphocytes, a form of white blood cell. In this disease, B cells grow and survive abnormally, leading to their accumulation in the bone marrow, lymph nodes, and spleen. Early symptoms often include fatigue and weakness. It is characterized by the overproduction of IgM paraprotein—a blood protein that can cause the blood to thicken and lead to complications such as vision issues, heart problems, hemolytic anemia, and neurological symptoms.

Bexobrutideg previously received the U.S. Food and Drug Administration’s Fast Track designation in December 2024 for the treatment of WM and Fast Track designation in January 2024 for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) after at least two lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor. In November 2024, the EMA granted PRIME designation to bexobrutideg for the treatment of adult patients with relapsed or refractory CLL/SLL after treatment with at least a BTK inhibitor and a BCL2 inhibitor.

About Bexobrutideg (NX-5948)

Bexobrutideg is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix previously has 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.

On July 7, 2025 Sona Nanotech Inc. (CSE: SONA) (OTCQB: SNANF) (the "Company", "Sona") an oncology-focused life sciences company developing innovative therapies based on its uniquely biocompatible gold nanorod technology, reported that a first dosing has been achieved in the previously announced early feasibility study of its Targeted Hyperthermia Therapy ("THT") cancer treatment (Press release, Sona Nanotech, JUL 7, 2025, View Source [SID1234654262]).

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Dr. Carman Giacomantonio, Sona’s CMO, commented, "Our unique therapy aims to modify tumors making them more visible to the immune system with a view to enabling an elimination of the cancer. As with any new technology, we are required to demonstrate that we can safely and feasibly deliver the treatment in the clinical setting. We have smartly designed this inaugural study to also provide us with some key, first ever reported, insights into its effect in human cancer. Success in this study will enable us to proceed to our next planned study that will more critically evaluate the biological effects and clinical outcomes of this exciting technology."

David Regan, CEO, commented, "Getting to this first dosing of a patient with our Targeted Hyperthermia Therapy is a milestone achieved through the culmination of years of research, toil and many preclinical studies. We plan to follow this critical first clinical step quickly with a second, more expansive human trial following further engagement with regulators, as well as a peer-reviewed article in a leading scientific journal detailing our findings. We also expect the learnings from this study to help inform on THT’s potential for complementing the treatment of other cancer types."

About the Study
The study is designed to assess THT’s safety, tolerability, and preliminary efficacy as measured by tumor growth inhibition and the extent to which it causes immune system engagement with the cancer. The study includes two treatments of Sona’s THT, one week apart, for patients with advanced melanoma who are, or have been on, standard of care immunotherapy protocols but have failed to respond or progressed during treatment. The study is anticipated to generate an initial read out of results this summer, with final results expected in the fall.

Technology will be evaluated for:

Ease of setting up and preparation for the treatment
Ease of administration of GNR’s in a variety of different tumors
Reproducibility in the clinical setting, i.e. the ability to train others to use the technology
Resource requirements, i.e. what additional resources are required in the clinical setting
Time required to administer the treatment in the clinical setting
Participants will be evaluated for:

Tolerability to the treatment itself
Adverse events during and following treatment
Clinical response, i.e. did the tumor change in any way after treatment
Pathological immune response, i.e. histological evidence of immune activation in the tumor that is directly relatable to the treatment itself.
Sona Nanotech believes that its THT cancer treatment may provide benefits over current standard of care immunotherapy treatments alone which have shown limited response rates and can have undesirable side effects.

On July 4, 2025 AB Science SA (Euronext – FR0010557264 – AB) reported that a confirmatory phase 3 trial of masitinib in metastatic castrate resistant prostate cancer (study AB22007) has been authorized by FDA and EMA (harmonized protocol approved through step 1 of Clinical Trials Information System), with a biomarker that targets patients with less advanced metastatic disease (Press release, AB Science, JUL 4, 2025, View Source [SID1234654249]).

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Professor Olivier Hermine, MD, President of the Scientific Committee of AB Science and member of the Académie des Sciences in France said, "The authorization of our confirmatory Phase 3 study by both the FDA and EMA represents a critical milestone for masitinib in metastatic castrate-resistant prostate cancer. With a validated biomarker guiding patient selection, this trial has the potential to establish the first targeted combination with docetaxel in nearly two decades for mCRPC."

Design of phase 3 study

Study AB22007 is a prospective, multicenter, randomized, double blind, placebo-controlled, 2-parallel groups, phase 3 study to confirm the efficacy and safety of docetaxel (IV 75 mg/m² plus prednisone for up to 10 cycles) plus masitinib 6.0 mg/kg/d, versus docetaxel plus placebo in metastatic castrate resistant prostate cancer (mCRPC).

The study will enroll 600 patients (randomization 1:1) with confirmed mCRPC eligible to docetaxel and with a biomarker (as measured by baseline alkaline phosphatase level) indicative of less advanced metastatic disease. The study’s primary endpoint will be radiographic progression free survival (rPFS), supported by overall survival as the first secondary endpoint.

Masitinib is positioned in metastatic castrate resistant prostate cancer eligible to docetaxel, a high unmet medical need

Masitinib is positioned in combination with docetaxel as a treatment of mCRPC patients who are eligible to docetaxel; that is to say, it is administered directly following resistance or relapse after the metastatic hormone-sensitive prostate cancer (mHSPC) treatments.

While there are numerous treatments in the mHSPC treatment space, there is currently no drug registered for use in combination with standard of care treatment docetaxel in patients who have relapsed on hormone treatments, i.e., patients with mCRPC, despite docetaxel having been approved almost 20 years ago.

Although localized disease is associated with high survival rates, metastatic prostate cancer still represents an unmet medical need with a 5-years survival rate of about 30% [1]. Up to 20% of men who undergo state-of-the art treatment for prostate cancer will develop CRPC within 5 years, and at least 84% of these will have metastases at the time of CRPC diagnosis [2]. Practically all patients with metastatic disease become resistant to androgen-deprivation therapy.

Prostate cancer is the most common cause of cancer in men, with 137.9 new cases per 100,000 men per year [2]. The estimated prevalence of people living with prostate cancer is 113 per 100,000 [3], with approximately 15% of the patients having mCRPC eligible to chemotherapy [4]. As such, the population with mCRPC eligible to chemotherapy is around 75,000 in the EU and 50,000 in the USA.

Results from study AB12003 demonstrated that the biomarker Alkaline Phosphatase predicts response of masitinib in mCRPC. The combination of masitinib plus docetaxel may provide a new first-line treatment option for mCRPC patients with low metastatic involvement.

Primary analysis:

AB12003 was a prospective, placebo controlled, double blind, randomized, phase 3 trial, evaluating masitinib (6.0 mg/kg/d) in combination with docetaxel (IV 75 mg/m² plus prednisone for up to 10 cycles) as a first-line treatment of mCRPC. Eligible patients were chemo-naïve with confirmed mCRPC, who had progressed on previous abiraterone treatment or were indicated for docetaxel treatment, and had a ECOG ≤1. Primary analysis was performed on a pre-specified targeted subgroup, defined as patients with baseline alkaline phosphatase levels (ALP) ≤250 IU/L, and on the overall population. Primary endpoint was progression free survival (PFS) (PCWG2 definition). The study was successful if improvement in median PFS relative to control reached a 3.9% level of significance for the target subgroup (alpha split with fallback procedure to conserve overall type-I error at 5% for the overall study cohort). Primary analysis was based on 450 patients in the targeted subgroup (ALP ≤ 250 IU/L). There was a total of 712 patients in the overall study cohort.

Masitinib (6.0 mg/kg/day) plus docetaxel confers a significant PFS benefit in mCRPC patients with ALP ≤ 250 IU/L. Hazard ratio of 0.79 [0.64;0.97] (p=0.0087), corresponding to a 21% reduction in risk of progression relative to control. Assessment of PFS rates was convergent with this primary outcome; 12, 18, and 24-month PFS rates showed significant improvement in favor of masitinib plus docetaxel relative to control: 1.6-fold (p=0.0035), 1.9-fold (p=0.0001) and 1.9-fold (p=0.0028), respectively.

ALP as a biomarker:

Importantly, a progressively greater masitinib treatment effect was observed for lower baseline ALP levels (less advanced metastatic disease), with a significant 47% reduced risk of progression in patients with ALP≤100 IU/L (hazard ratio=0.53, p=0.002).

The efficacy and response of masitinib was in fact correlated to the level of ALP.

The use of biomarker ALP for the confirmatory phase 3 study has been validated by FDA and EMA.

The establishment of a biomarker predictive of the response to masitinib is a potentially important discovery.

ALP measures the involvement in the bones and in the liver of metastasis.

When used sufficiently early, masitinib in combination with docetaxel was able to slow down the progression of the metastatic cancer even resistant to hormone treatments.

The masitinib plus docetaxel safety profile was acceptable with respect to control; consistent with the known masitinib profile and no new safety signals observed.

Historically, there has been a high failure rate of trials studying combinations of docetaxel and new targeted agents, with study AB12003 being a rare example of a phase 3 clinical trial that showed improvement in progression-free survival (PFS) for masitinib in combination with docetaxel.

Patent protection until 2042

Based on the results from AB12003 study, AB Science filed a patent application relating to methods of treating mCRPC (i.e. a secondary medical use patent) with its lead compound masitinib.

The European Patent Office has granted this patent (EP4175639). It provides protection until 2042 for masitinib and related compounds for treatment of mCRPC in the patient subpopulation with low metastatic involvement (as measured by baseline alkaline phosphatase levels), which is the patient population in the approved phase 3 study of masitinib in mCRPC. Counterpart patent applications have also been filed in other major international markets, including the United States.

On July 4, 2025 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting Smart Allostery platform-identified regulatory sites on proteins referred to as "natural hotspots," reported the presentation of preclinical data from the Company’s CARD11-BCL10-MALT1 (CBM) signalosome program at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2025 (Press release, HotSpot Therapeutics, JUL 4, 2025, View Source [SID1234654250]).

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The CBM signalosome is a molecular hub that serves as a key regulator of multiple oncogenic pathways, including NFkB, JNK, mTORC1 and MYC. As such, the CBM signalosome serves as a critical regulator of tumor development and survival, particularly in KRAS-driven colorectal cancer (CRC), as well as other KRAS-driven cancers, including pancreatic and lung cancer. Leveraging the Company’s proprietary Smart Allostery platform, HotSpot has discovered small molecule CBM signalosome inhibitors that bind and inactivate the complex, with preclinical data demonstrating dose-dependent tumor inhibition and regression in multiple KRAS-driven tumor models.

"While KRAS activation is a prominent genetic feature of CRC, KRAS inhibitors do not yield deep or durable responses for the vast majority of CRC patients. For the first time, we have shown that KRASG12X CRC depends on the CBM signalosome for survival, supporting the significant potential of a CBM signalosome inhibitor to transform the treatment landscape of KRASG12C CRC, as well as additional KRAS-associated solid tumors," said Geraldine Harriman, Ph.D., Chief Scientific Officer of HotSpot Therapeutics. "Leveraging our Smart Allostery platform, we have developed potent inhibitors of the CBM signalosome complex, with robust in vitro and in vivo data demonstrating apoptosis and tumor growth inhibition and regression in KRASG12C CRC, providing support for the profound clinical potential of a CBM signalosome inhibitor."

The poster presentations describe the following data:

HotSpot’s CBM signalosome inhibitors demonstrated selectively induced potent apoptosis in KRASG12 CRC cell lines, outperforming KRAS, BCL2 and Bcl-xL inhibitors.
In combination with a KRAS inhibitor, HotSpot’s CBM signalosome inhibitor achieved complete suppression of downstream signaling in KRASG12X cell lines.
HotSpot’s CBM signalosome inhibitor demonstrated dose-dependent tumor inhibition or regression both alone and in combination with a KRAS inhibitor in multiple in vivo models.