On July 7, 2025 Mustang Bio, Inc. ("Mustang" or the "Company") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell therapies into potential cures for difficult-to-treat cancers, reported that the U.S. Food and Drug Administration ("FDA") has granted Orphan Drug Designation to Mustang for MB-101 (IL13Ra2-targeted CAR T-cells) for the treatment of recurrent diffuse and anaplastic astrocytoma (astrocytomas) and glioblastoma (GBM) (Press release, Mustang Bio, JUL 7, 2025, View Source [SID1234654265]).

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The FDA grants Orphan Drug Designation to drugs and biologics that are intended for safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. Orphan Drug Designation provides certain incentives, such as tax credits toward the cost of clinical trials upon approval and prescription drug user fee waivers. If a product receives Orphan Drug Status from the FDA, that product is entitled to seven years of market exclusivity for the disease in which it has Orphan Drug designation, which is independent from intellectual property protection.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are thrilled that MB-101 received Orphan Drug Designation on time and with a designation that is broader than the indication proposed. The Orphan Drug Designation for MB-101, coupled with the Orphan Drug Designation granted previously for MB-108, is strong validation for our science, as we hope to advance MB-101, in combination with MB-108, as a potential treatment option for patients living with malignant glioma, including patients with recurrent glioblastoma ("GBM") and high-grade astrocytomas. Our novel therapeutic strategy, combining our MB-101 CAR-T cell therapy with our MB-108 oncolytic virus, leverages MB-108 to reshape the tumor microenvironment ("TME") to make cold tumors "hot," thereby potentially improving the efficacy of MB-101 CAR-T cell therapy. This progress demonstrates our dedication to exploring new possibilities for improving outcomes in patients with challenging-to-treat cancers."

As previously reported, preclinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting in 2022 supported a combination therapy to potentially optimize results to treat recurrent GBM. The combination leverages MB-108 to reshape the TME and make cold tumors "hot," thereby potentially improving the efficacy of MB-101 CAR-T cell therapy. Data presented separately on MB-101 and MB-108 showed that administration of these therapies was well tolerated in recurrent GBM patients. As reported in City of Hope’s 2024 Nature Medicine paper, 2 patients treated solely with MB-101 who had high levels of intratumoral CD3+ T cells pre-therapy (i.e., "hot" tumors) achieved complete responses lasting 7.5 and 66+ months, respectively. Importantly, of the 57 City of Hope Phase 1 patients evaluable for survival in that paper, these 2 complete responses were observed in the cohort of 3 patients with the "hottest" tumors prior to treatment with MB-101. Phase 1 clinical trials of MB-101 at City of Hope and of MB-108 at The University of Alabama at Birmingham continue to enroll patients.

The Company’s ability to further develop the MB-109 program for recurrent GBM and high-grade astrocytomas is contingent upon raising additional funding and / or consummating a strategic partnership.

About MB-109 (MB-101 (IL13Rα2 targeted CAR-T cells) + MB-108 oncolytic virus)
MB-109 is Mustang’s designation for the treatment regimen combining MB-101 (IL13Rα2‐targeted CAR-T cell therapy licensed from City of Hope) with MB-108 (HSV-1 oncolytic virus licensed from Nationwide Children’s Hospital). The combination is designed to leverage MB-108 to make cold tumors "hot" and potentially improve the efficacy of MB-101 CAR-T cell therapy. MB-108 oncolytic virus is first injected to infect tumor cells which, in turn, leads to reshaping of the TME through recruitment of endogenous CD8- and CD3-positive effector T-cells. This inflamed TME potentially permits MB-101 CAR-T cells injected into and around the tumor to better infiltrate into and throughout the tumor mass, undergo activation and, ideally, effect tumor cell killing.

On July 7, 2025 Agenus Inc. (Nasdaq: AGEN) a leader in immuno-oncology innovation, reported that its botensilimab and balstilimab (BOT/BAL) combination achieved a two-year survival rate of 42% along with a now more mature 21-month median overall survival (OS) in an expanded cohort of 123 patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases (NLM) (Press release, Agenus, JUL 7, 2025, View Source [SID1234654264]). Agenus also confirmed that it has reached agreement with the U.S. Food and Drug Administration (FDA) on the design of the global BATTMAN Phase 3 trial. The FDA waived the need for a BOT monotherapy arm, allowing for a simple two-arm study design. These new BOT/BAL data were reported at the 2025 ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress (ESMO-GI) in Barcelona, Spain, along with regulatory updates from its July 1, 2025 End-of-Phase 2 (EoP2) meeting with the U.S. Food and Drug Administration (FDA).

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ESMO‑GI Clinical Highlights

The new data presented at ESMO (Free ESMO Whitepaper)-GI represent an approximate 40% increase in number of patients (n=123) compared to earlier reports published in Nature Medicine in 2024. The expanded dataset demonstrates continued durability of tumor responses and median overall survival approaching two years in an immunotherapy-resistant treatment setting. Among these 123 heavily pretreated MSS mCRC patients (third-line or later) treated with BOT/BAL, the confirmed objective response rate (ORR) was 20%, with a median duration of response (DOR) of 16.6 months. The disease control rate (DCR, responses plus stable disease) was 69%. Notably, median overall survival (OS) reached 20.9 months, with 42% of patients still alive at two years in this refractory population. Patients in fourth-line or later (n=37), having exhausted all standard therapies, saw similar benefits, with a ~19% ORR and 43% two-year survival. These findings are particularly meaningful in this refractory population for which best supportive care has been historically limited to roughly 5-8 months median overall survival.

No new safety signals were observed. Immune-related side effects were manageable and no treatment-related deaths occurred. The combination was tolerated across dose levels.

"These results reinforce the consistency and durability of the botensilimab plus balstilimab combination in a population that has historically seen minimal benefit from immune checkpoint blockade," said Dr. Benjamin Schlechter of Dana-Farber Cancer Institute, who presented the data. "For patients with MSS colorectal cancer who have exhausted standard therapies, this combination is showing the kind of meaningful, long-lasting benefit we rarely see in this setting. It has the potential to fundamentally shift how we treat this disease."

"Deep, durable responses and survival plateaus emerging at two years and beyond are rarely seen in microsatellite stable refractory colorectal cancer – they are usually only seen in highly immunogenic tumors," said Dr. Steven O’Day, Chief Medical Officer of Agenus. "These data reinforce the potential for a chemo‑free option in a population with limited alternatives."

FDA Meeting Outcomes

Official minutes from the July 1, 2025 End-of-Phase 2 (EoP2) meeting reflect a meaningful shift in FDA alignment since July 2024, establishing two new areas of agreement:

Contribution of components – FDA wrote that the current data "appears to support" balstilimab’s contribution to the combination’s clinical activity and therefore a registrational Phase 3 trial may proceed without a BOT monotherapy arm.
Phase 3 registrational trial – BATTMAN (CCTG CO.33): FDA and Agenus aligned on the core design of this global registration study for BOT/BAL. Agenus is incorporating the Agency’s feedback and will initiate BATTMAN in Q4 2025.
During the discussion on July 1, 2025, the FDA stated that it continues to recommend Agenus conduct a randomized controlled trial to support the approval of BOT/BAL in the metastatic setting and the demonstrated magnitude of treatment effect "does not appear to meet the standard of reasonably likely to predict benefit." Agenus and key experts in oncology and immunotherapy, including those present in the FDA meeting—strongly believe that the BOT/BAL data meets the standard of Subpart E given the magnitude, durability, and urgent unmet need in this patient population.

Jennifer Buell, Ph.D., Executive Chairwoman of Agenus, commented: "FDA’s acknowledgement of balstilimab’s role and its constructive guidance on the Phase 3 trial mark a pivotal step forward. We have incorporated the Agency’s input and are moving swiftly to launch BATTMAN, while continuing to mature our existing dataset. Guided by Commissioner Makary’s commitment to accelerate promising therapies, we intend to use every expedited pathway—Fast Track, Real-Time Oncology Review, the new Commissioner’s National Priority Voucher Program, and other accelerated mechanisms—to bring this chemo-free option to patients who have exhausted all other treatments."

Clinical Urgency

"Colorectal cancer is rising fastest in people under 50 and is projected to become the leading cause of cancer death in that age group by 2030," said Richard Goldberg, M.D., Chief Development Officer, Agenus. "Given the dismal five‑to‑eight‑month median survival with current late‑line therapies, making BOT/BAL available quickly is not just prudent—it is imperative."

2H2025 Catalysts

Launch Global Registrational Trial (BATTMAN): Initiate BATTMAN in 4Q2025; rapidly accrue trial designed to confirm OS benefit and registration.
Advancing Earlier-Line CRC: Ongoing data of BOT/BAL in 1L and neoadjuvant MSS CRC will inform upcoming discussions with regulatory agencies on potential pathways for expanded development.
Global Clinical Infrastructure: Advancing collaboration with Zydus and other strategic partners to support rapid global enrollment, high-quality data generation, and future regional access.
Upcoming Data Presentations: Updated data of BOT/BAL in CRC and other tumors to be presented at major oncology congresses in Q4 2025, reinforcing the combinations activity across solid cancers.
Regulatory Engagement & Expedited Pathways: Ongoing collaboration with Dr. Makary, the FDA, and senior U.S. government stakeholders to pursue expedited regulatory mechanisms, including Accelerated Approval, the Commissioner’s National Priority Voucher Program, and Real-Time Oncology Review to address the current cancer crisis.

On July 7, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that it has completed patient enrollment in its Phase 3 UTOPIA clinical trial of UGN-103 (mitomycin) for intravesical solution, a next-generation formulation in development for the treatment of recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) (Press release, UroGen Pharma, JUL 7, 2025, View Source [SID1234654263]).

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The UTOPIA trial enrolled 99 patients across multiple centers globally. UGN-103 uses UroGen’s proprietary sustained release RTGel technology, a reverse-thermal hydrogel that enables sustained drug release and prolonged bladder exposure. UGN-103 is designed to offer improvements over ZUSDURI (mitomycin) for intravesical solution, including a shorter manufacturing process and simplified reconstitution procedure.

"Completing enrollment in the UTOPIA trial marks a significant milestone in our efforts to advance UGN-103 as a next-generation treatment option for patients with recurrent LG-IR-NMIBC," said Michael Louie, M.D., EVP, Medical Affairs and Clinical Development, UroGen. "UGN-103 represents a pivotal advancement in our pipeline, aiming to deliver the same non-surgical benefits to patients as ZUSDURI, while also enhancing operational efficiency and convenience for providers."

The UTOPIA trial is a single-arm, multicenter study evaluating the efficacy and safety of UGN-103. All enrolled patients receive 75 mg of UGN-103 via intravesical instillation once weekly for six weeks. The primary endpoint is complete response rate at three months, with responders entering a follow-up phase of up to 12 months to assess durability of response. For more information on the UTOPIA study, please visit clinicaltrials.gov/NCT06331299.

UroGen received a Notice of Allowance from the U.S. Patent and Trademark Office in September 2024 covering the use of UGN-103 for LG-IR-NMIBC, with patent protection expected through December 2041.

About UGN-103
In January 2024, UroGen entered into a licensing and supply agreement with medac to develop UGN-103 for LG-IR-NMIBC. UGN-103 is an innovative mitomycin formulation that aims to streamline manufacturing and reconstitution processes while providing intellectual property coverage until December 2041. It utilizes UroGen’s RTGel technology for prolonged mitomycin exposure.

About ZUSDURI
ZUSDURI (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, approved for the treatment of adults with recurrent LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, ZUSDURI is delivered directly into the bladder in an out-patient procedure by a trained healthcare professional using a urinary catheter to enable the treatment of tumors by non-surgical means. ZUSDURI is expected to be available in the U.S. on or around July 1, 2025. In the interim, patients can visit ZUSDURI.com for more information.

About Non-Muscle Invasive Bladder Cancer (NMIBC)
LG-IR-NMIBC affects around 82,000 people in the U.S. every year and of those, an estimated 59,000 are recurrent. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. Guideline recommendations for the management of NMIBC include TURBT as the standard of care. Up to 70 percent of NMIBC patients experience at least one recurrence, and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures. Learn more about non-muscle invasive bladder cancer at www.BladderCancerAnswers.com.

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 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.