On April 28, 2025 Be Biopharma, Inc. ("Be Bio"), a clinical-stage company pioneering the discovery and development of engineered B Cell Medicines (BCMs), reported that it will present at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 28th Annual Meeting being held in New Orleans, May 13-17, 2025 (Press release, Be Biopharma, APR 28, 2025, View Source [SID1234652220]).

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Details regarding the Be Biopharma presentations at the conference are as follows:

Oral Presentation Title: Ex Vivo Gene Editing of Autologous B Cells Produce Sustained Levels of Tissue Nonspecific Alkaline Phosphatase In Vivo for the Potential Treatment of Hypophosphatasia
Presenter: Hanlan Liu, Ph.D., MBA, SVP, Head of Late Research and NCD, Be Biopharma
Date: May 17, 2025
Presentation Time: 10:45 – 11:00 AM CT
Session Title: B-Cell and Solid Organ Therapies
Session Time: 10:15 AM – 12:00 PM CT
Session Room: 278-282

The oral presentation will include nonclinical data for Be Biopharma’s BE-102 program, a novel B cell therapy developed as a potential treatment of Hypophosphatasia (HPP). HPP is caused by deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity, resulting from pathogenic mutations in the ALPL gene, which leads to multi-systemic clinical complications including deficient bone mineralization. Enzyme replacement therapy (ERT) is the only approved treatment for HPP which requires frequent lifelong injections. ERT is only available for perinatal/infantile- and juvenile-onset forms of HPP and weekly injections are associated with common side effects that can significantly affect a patient’s quality of life. BE-102 was developed to address these limitations. BE-102 is manufactured from primary human B cells by isolating, activating, and precision engineering with CRISPR/Cas9 followed by AAV-mediated delivery of a DNA donor template for the insertion of human ALPL gene into the CCR5 locus (a safe harbor locus). In vitro pharmacology results demonstrate that BE-102 secretes active TNSALP, which is capable of rescuing calcium deposit inhibited by inorganic pyrophosphate (PPi), a substrate which accumulates in people with HPP. In vivo studies were conducted in immune-deficient NOG-hIL6 mice, confirming long-term engraftment and continuous production of active TNSALP in vivo following a single IV administration of BE-102. Be Biopharma’s in vitro and in vivo pharmacology and safety data established nonclinical proof-of-concept that BE-102 has the potential to be a disease-modifying therapy for people with HPP by providing long-lasting active TNSALP, with the flexibility to be titratable and redosable as needed.

Poster Title: Exploration of Allogeneic Shielding Strategies by Precise CRISPR/Cas9 Genome Engineering of Primary Human B Cells to Enable Off-the-shelf B Cell Medicines for Sustained Delivery of in vivo Biologics
Presenter: Xuqing Zhang, Ph.D., Director, Immunology, Be Biopharma
Date: May 13, 2025
Time: 6:00 – 7:30 PM CT
Session Title: Tuesday Poster Reception
Session Room: Poster Hall, Hall I2
Final Abstract Number: 777

The abstract highlights Be Biopharma’s approach using both in vitro and in vivo assays to determine the potential of B Cell Medicines (BCMs) as an allogeneic off-the-shelf cell therapy without additional engineering and ways to enhance hypoimmunogenicity via CRISPR/Cas9 genome engineering. The data demonstrates BCMs are immunologically stealthy and can be further engineered to evade host immune responses, opening the possibility of exploring them as off-the-shelf cellular therapies without HLA matching for broader patient access.

About Engineered B Cell Medicines – A New Class of Cellular Medicines
The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, and over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable, and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.

On April 28, 2025 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company working to develop a new class of drugs based on targeted protein degradation, reported data from preclinical combination studies of ARV-393, the company’s investigational PROteolysis TArgeting Chimera (PROTAC) B-cell lymphoma 6 protein (BCL6) degrader (Press release, Arvinas, APR 28, 2025, View Source [SID1234652219]). BCL6 is a transcriptional repressor protein and a known driver of B-cell lymphomas. Data demonstrated synergistic antitumor activity, including complete regressions, in combination with standard of care (SOC) chemotherapy, SOC biologics, and investigational oral small molecule inhibitors (SMIs) in high grade B-cell lymphoma (HGBCL) and aggressive diffuse large B-cell lymphoma (DLBCL) models. The results from these preclinical studies were shared in a poster presentation at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in Chicago, Illinois.

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Key findings from the studies included:

ARV-393 in combination with SOC chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]), induced significantly greater tumor growth inhibition compared with rituximab, CHOP, R-CHOP, or ARV-393 alone, with complete tumor regressions in all mice treated with the ARV-393 and R-CHOP combination.
ARV-393 in combination with SOC biologics targeting CD20 (rituximab), CD19 (tafasitamab), or CD79b (polatuzumab vedotin) resulted in tumor regressions and demonstrated significantly stronger tumor growth inhibition compared with each agent alone.
In preclinical models, ARV-393 increased CD20 expression, providing additional support for the exploration of combinations with CD20-targeted agents and in the context of low or loss of CD20 expression.
ARV-393 in combination with investigational small molecule inhibitors targeting clinically validated oncogenic drivers of lymphoma, such as BTK (acalabrutinib), BCL2 (venetoclax), or EZH2 (tazemetostat), resulted in superior tumor growth inhibition compared with each agent alone, with tumor regressions in all mice treated with the combinations.
"Given that combination regimens are the foundation of lymphoma treatment, we are encouraged by the strength of these preclinical combination data, which demonstrate complete tumor regressions in aggressive lymphoma models," said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. "We believe these preclinical data demonstrate potential for broad combinability of ARV-393 and provide a compelling rationale for considering combination strategies as we work to bring forward new therapeutic options for lymphoma patients."

A Phase 1 study of ARV-393 is enrolling patients with relapsed/refractory non-Hodgkin lymphoma, including DLBCL (NCT06393738).

Additional detail on the ARV-393 data presentation at AACR (Free AACR Whitepaper) 2025:

Poster Title: ARV-393, a PROteolysis TArgeting Chimera (PROTAC) BCL6 Degrader, Combined With Biologics or Small-Molecule Inhibitors Induces Tumor Regressions in Diffuse Large B-Cell Lymphoma Models
Abstract: 1655
Session Title: Degraders and Glues 2
Session Type: Experimental and Molecular Therapeutic
Location: Poster Section 18
Poster Board Number: 15
Date: Monday, April 28, 2025
Lecture Time: 9:00 a.m. – 12:00 p.m. CT

About ARV-393
ARV-393 is an investigational, orally bioavailable PROteolysis TArgeting Chimera (PROTAC) designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. During B-cell development, tightly controlled BCL6 protein expression regulates >600 genes to facilitate rapid B-cell proliferation and tolerance of somatic hypermutation and gene recombination for antibody generation. Deregulated BCL6 expression is common in B-cell lymphoma and promotes cancer cell survival, proliferation, and genomic instability. PROTAC-mediated degradation has the potential to address the historically undruggable nature of BCL6. ARV-393 is currently in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma.

On April 28, 2025 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported that it has successfully closed a registered direct offering (the "offering") whereby an affiliate of Oramed Pharmaceuticals Inc. ("Oramed") (Nasdaq: ORMP) (TASE: ORMP) purchased 14,110,121 of Alpha Tau’s ordinary shares, no par value, at a purchase price of $2.612 per ordinary share (Press release, Alpha Tau Medical, APR 28, 2025, View Source [SID1234652216]). The offering closed on April 28, 2025.

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The total gross proceeds of the offering were approximately $36.9 million, before deducting estimated offering expenses payable by Alpha Tau. Alpha Tau intends to use the net proceeds from the offering for general corporate purposes, including research and development-related purposes in connection with its product candidates, for expansion of its manufacturing capabilities and for potential commercialization of its product candidates.

In addition, the parties have entered into an agreement whereby an affiliate of Oramed will provide Alpha Tau with certain strategic services (investor relations and public relations) over the next three years in exchange for payments from Alpha Tau as well warrants to purchase additional Alpha Tau shares.

Alpha Tau CEO Uzi Sofer commented, "We are delighted to welcome Oramed as a strategic partner and to leverage their extensive expertise in navigating diverse capital markets channels. This investment comes at the perfect time for Alpha Tau given the rapid expansion of our business activities, including four parallel trial approvals in the U.S., expansion into trials in multiple internal organs, and continued expansion of our manufacturing capacity and pre-commercial preparations. We look forward to a long and fruitful relationship with Oramed."

Oramed CEO Nadav Kidron added, "We are incredibly excited about this alliance with Alpha Tau. We have tremendous conviction in the strength of the Alpha DaRT technology and the Alpha Tau management team. We anticipate significant advancements and milestone achievements as they execute their clinical and commercial roadmap."

A registration statement on Form F-3 relating to the securities to be sold in the registered direct offering has been filed with the U.S. Securities and Exchange Commission (the "SEC") and was declared effective on April 13, 2023. This registered direct offering was made only by means of a prospectus. A copy of the prospectus supplement and the accompanying prospectus relating to this offering was filed with the SEC and may be obtained for free by visiting EDGAR on the SEC’s website at www.sec.gov

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On April 27, 2025 ImmVira reported the Phase I clinical results of its oncolytic Herpes Simplex Virus ("oHSV") product MVR-C5252 targeting malignant glioma through poster presentation at American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") annual meeting (Press release, Immvira, APR 27, 2025, View Source [SID1234652208]).

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According to industry data, malignant glioma, a highly aggressive and recurrent brain cancer, has a five-year survival rate of less than 5%. Developed on ImmVira’s proprietary OVPENS platform, MVR-C5252 is specifically engineered with designed attenuation to achieve on-target malignant gliocyte killing and armed with PD-1 antibody and IL-12, for the synergistic anti-tumor effects of "oncolysis + immune activation". This innovative product has obtained Investigational New Drug approval in both the U.S. and China, as well as Orphan Drug Designation from the FDA.

The Phase I trial, for which the clinical study results were released, was conducted in collaboration with Duke University, a renowned institution with expertise in oncolytic virotherapy, immunotherapy, and CNS treatments. Unlike the commonly used Ommaya reservoir, MVR-C5252 is delivered intracranially via convection-enhanced delivery ("CED"). This approach can provide slow and sustained positive pressure to the target brain area via an implanted catheter to ensure even drug distribution, enabling multiple dosing while bypassing the blood-brain barrier. To date, five patients with recurrent high-grade glioma have received MVR-C5252 treatments.

In Stage 1A of the study, three patients received 5×10⁶ PFU and completed the dose-limiting toxicity ("DLT") period. Serial cytokine analysis of cerebrospinal fluid ("CSF") showed dynamic immune responses and intended biologic activity, with measurable changes in cytokine concentrations post-infusion. In addition, no serious adverse events ("SAEs"), DLTs, or Grade 3–5 adverse events ("AEs") occurred. The only reported Grade 1–2 AEs included fatigue, flu-like symptoms, and cognitive disturbance, indicating a favorable safety profile of MVR-C5252 delivered via CED.

Dr. Grace Guoying Zhou, ImmVira’s Chairwoman and CEO, said, "We are committed to developing advanced therapies featuring novel modalities using oHSV and engineered exosomes, to address complex and challenging diseases. After years of parallel development and in-depth explorations in both the U.S. and China, we have strategically focused on malignant glioma for the development of MVR-C5252, leveraging HSV-1’s unique biological and translational medical characteristics and in line with highly unmet medical needs and substantial market potential. Our collaboration with Duke University, a global leader in glioma research and treatment, will accelerate clinical development of this innovative therapy, delivering a new solution for this type of severe life-threatening diseases."

On April 27, 2025 Johnson & Johnson (NYSE: JNJ) reported new data from Cohort 2 of the pivotal Phase 2b SunRISe-1 study evaluating TAR-200—an intravesical gemcitabine releasing system—for patients with certain types of bladder cancer (Press release, Johnson & Johnson, APR 27, 2025, View Source;johnsons-tar-200-monotherapy-demonstrates-highest-complete-response-rate-with-sustained-clinical-benefits-in-patients-with-certain-types-of-bladder-cancer-302438939.html [SID1234652207]). The findings demonstrate the highest complete response rate without reinduction with more than half of responders remaining cancer-free for at least 12 months. These results highlight the potential of TAR-200 as a breakthrough for people with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC) with carcinoma in situ (CIS), with or without papillary tumors who are ineligible or refuse radical cystectomy (RC). These results were featured in the Paradigm-Shifting, Practice-Changing Clinical Trials in Urology plenary session at the 2025 American Urological Association (AUA) Annual Meeting.1

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"Treatment with TAR-200 has long-lasting effectiveness. More than 82 percent of patients achieved a complete response, and of those that initially responded to treatment, more than half showed no signs of cancer at one year," said Joseph Jacob*, M.D., MCR, Associate Professor of Urology at Upstate Medical University and presenting author. "These findings represent the highest complete response rate observed for patients with HR-NMIBC and underscore the potential of TAR-200 to provide long-lasting cancer control for patients."

"Bladder cancer is one of the ten most common cancers worldwide, yet treatment options have remained largely unchanged for over 40 years, leaving patients with few choices if initial BCG therapy does not work," said Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Johnson & Johnson Innovative Medicine. "TAR-200 is designed to allow for sustained delivery of medication directly into the bladder through a brief and routine procedure, which benefits patients. These data now show patients can remain cancer-free for a meaningful period of time, marking a significant step forward for those facing this challenging disease."

As of March 2025, 82.4 percent of the 85 enrolled patients in the study achieved a complete response (CR) (95 percent confidence interval [CI], 72.6-89.8), meaning their cancer was undetectable following treatment. This high response rate translated into sustained disease control, with 52.9 percent of responders maintaining complete response at one year. The median duration of response (DOR) was 25.8 months (95 percent CI, 8.3-not estimable), indicating that many patients remained cancer-free for over two years without the need for reinduction therapy. At 12 months, 86.6 percent (95 percent CI, 76.6-92.6) of responders remained cystectomy-free. Importantly, the treatment was well-tolerated, with most adverse events being mild urinary symptoms. These findings show that TAR-200 offers a highly effective and durable treatment option for patients with certain types of BCG-unresponsive HR-NMIBC.

Most treatment-related adverse events (TRAEs) were mild and manageable. Overall, 71 patients (83.5 percent) experienced TRAEs, the majority of which were low-grade urinary symptoms, such as bladder irritation or discomfort. Eleven patients (12.9 percent) experienced Grade 3 or higher TRAEs, and five patients (5.9 percent) reported serious TRAEs. Only three patients (3.5 percent) discontinued treatment due to TRAEs, and there were no treatment-related deaths.

TAR-200 is inserted directly into the bladder by a healthcare professional in a brief outpatient procedure, without the need for anesthesia. Designed to remain in the bladder, it does not interfere with daily activities and provides sustained release of treatment throughout the day. To date, TAR-200 has been placed more than 10,000 times as part of the SunRISe clinical program.

Earlier results from Cohort 2 were previously presented at the 2024 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and at the 2024 American Urological Association (AUA) Annual Meeting. In January 2025, Johnson & Johnson announced the initiation of a new drug application with the FDA for TAR-200 under the Real-Time Oncology Review (RTOR) program.

About TAR-200
TAR-200 is an investigational intravesical gemcitabine releasing system. In January 2025, Johnson & Johnson announced the initiation of a new drug application with the FDA for TAR-200 under the real-time oncology review (RTOR) program. In December 2023, the FDA granted Breakthrough Therapy Designation (BTD) to TAR-200 for the treatment of adult patients with BCG-unresponsive HR-NMIBC with CIS who are ineligible for or have elected not to undergo radical cystectomy. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with MIBC in SunRISe-4, and NMIBC in SunRISe-1, SunRISe-3 and SunRISe-5.

About SunRISe-1, Cohort 2
SunRISe-1 (NCT04640623) is an ongoing Phase 2b, randomized, open-label, multicenter study evaluating the efficacy and safety of TAR-200, an intravesical gemcitabine releasing system, in patients with BCG-unresponsive HR-NMIBC who are ineligible for, or elected not to undergo, radical cystectomy. Cohort 2 specifically enrolls patients with carcinoma in situ, with or without papillary disease, treating them with TAR-200 monotherapy. The primary endpoint for Cohort 2 is CR rate at any time point. Secondary endpoints include duration of response (DOR), overall survival (OS), pharmacokinetics, quality of life, safety and tolerability.

About High-Risk Non-Muscle-Invasive Bladder Cancer
High-risk non-muscle-invasive bladder cancer is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to muscle invasive bladder cancer compared to low-risk NMIBC.2,3 HR-NMIBC makes up 15-44 percent of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS.4 Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.5,6 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.