On April 28, 2025 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported research data on TALEN-mediated non-viral transgene insertion for advancing cellular and gene therapies, and advancements in genetic editing using base editors (TALEB), at the Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) annual meeting, that will be held on May 13-17, 2025 in New Orleans (Press release, Cellectis, APR 28, 2025, View Source [SID1234652224]).

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The data are presented in two posters:

Title: TALEN- Mediated non-viral Transgene Insertion for the Advancement of Cellular and Gene Therapies.

Cell and gene therapy approaches can use gene-editing tools and introduce transgenes to modify disease-associated genes, thus providing a potential therapeutic solution for a wide array of diseases.

In this work, Cellectis combines TALEN-mediated gene editing with non-viral delivery of transgene for advancing cellular and gene therapies, and explores gene insertion-efficacy and cellular health using single-stranded DNA (ssDNA) for payload delivery in different cell types.

This innovative approach has the potential to address the challenges associated with traditional lentiviral viral methods or AAV-mediated transgene insertion such as manufacturing constraints, potential genomic toxicities or limited payload size.

Research data show:

Non-viral methods for gene editing: TALEN mediated gene editing combined with non-viral templates (linear and circular ssDNA) can be used for highly efficient gene insertion in T-cells as well as hematopoietic stem and progenitor cells (HSPCs) promoting viability and insertion specificity
Advantages of Circular ssDNA over viral vectors: Transcriptomic analysis and in vivo data demonstrate that CssDNA-mediated cell engineering allows better maintenance of HSPC fitness as well as more stable gene editing, compared to traditional viral donor template-mediated transgene delivery.
« The implementation of these gene-editing techniques holds significant potential for the development of next-generation therapies, aiming to provide alternative efficient, and safe therapeutic options for patients with cancer, autoimmune diseases, monogenic disorders, and various other conditions. » said Beatriz Aranda Orgilles, Ph.D., Associate Director – IO and business development analyst at Cellectis.

Title: High fidelity C-to-T editing with base editors

TALE base editors (TALEB) are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and a uracil glycosylase inhibitor (UGI). The C-to-T class of TALEB edits double-stranded DNA by converting a cytosine (C) to a thymine (T) and does not involve DNA strand nick.

Cellectis has developed a method to characterize the efficiency of this conversion and examined various factors influencing TALEB activity. This method also takes advantage of a highly precise and efficient knock-in of ssODN in primary T cells to develop an assay to assess how the composition and spacer variations of target sequences affect TALEB activity/efficiency.

Research data show:

Efficiency of C-to-T editing: TALEB enables efficient conversion of C to T. Variations in target sequences and surrounding bases affecting editing efficiency. An educated choice of the TALEB architecture further allows to control the editing outcome.
Assessment of off-target editing risks: Studies have been conducted to evaluate off-target editing, showing no detectable editing in primary cells at previously described sites, highlighting the specificity of TALEB for potential therapeutic applications.
«It is inspiring to see the advancement of Cellectis’ TALE technology into a new tool that is available in our gene editing toolbox. Our ability to understand and fine-tune the editing capacity of TALE base editors has equipped us with another efficient and specific approach that can be used to support novel gene editing and gene therapy applications. » said Louisa Mayer, Ph.D., Scientist II and Supervisor – Innovation & Gene Editing at Cellectis.

Overall, the results of this study enhance the control and use of TALEB, allowing for the design of highly efficient and specific TALEB compatible with future therapeutic applications.

The abstracts are live on the ASGCT (Free ASGCT Whitepaper) website. The posters will be available on Cellectis’ website the first day of the event.

On April 28, 2025, BeiGene, Ltd. (the "Company") reported its 2024 Annual Report (the "STAR Annual Report") with the Science and Technology Innovation Board (the "STAR Market") of the Shanghai Stock Exchange, which was prepared in accordance with the listing rules of the STAR Market and the applicable securities laws and regulations of the Peoples’ Republic of China (the "PRC" and the "PRC Securities Laws") (Press release, BeiGene, APR 28, 2025, View Source [SID1234652221]). The STAR Annual Report is available to the public in Chinese language only on the website maintained by the Shanghai Stock Exchange at www.sse.com.cn.

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As required by the PRC Securities Laws, the STAR Annual Report contains additional financial information of the Company’s gross profit margin ratio, research and development expenses allocated by key products and other research and development projects and production, sales and inventory stock units for the year ended December 31, 2024 (the "Reporting Period"), prepared in accordance with the China Accounting Standards for Business Enterprises – Basic Standard ("CAS") and other applicable PRC accounting rules, guidance and interpretations (together with CAS, "PRC GAAP"), including but not limited to the China Securities Regulatory Commission’s Compilation Rule for Information Disclosure by Companies Offering Securities to the Public No. 15 – General Rules for Financial Statement (2023 revised), and Compilation Rule for Information Disclosure by Companies Offering Securities to the Public No. 24-Special Provisions on Information Disclosure in Financial Statements of Pilot Innovative Red-chip Companies on the Sci-Tech Innovation Board. The key differences between such financial information prepared in accordance with PRC GAAP and those prepared in accordance with accounting principles generally accepted in the United States ("U.S. GAAP") for the Reporting Period, which was previously filed with the U.S. Securities and Exchange Commission, are summarized below.

Key Differences between PRC GAAP and U.S. GAAP

Share-based Compensation

Under U.S. GAAP, the Company elects to recognize share-based compensation expenses using the straight-line method for all employee equity awards granted with graded vesting based on service conditions, provided that the amount of compensation cost recognized at any date is at least equal to the portion of the grant-date value of the options that are vested as of that date.

Under PRC GAAP, the Company recognizes share-based compensation expense using the accelerated method for all employee equity awards granted with graded vesting.

Under PRC GAAP, the excess tax benefit resulting from the pre-tax deductible amount arising from U.S. employee share-based payments over the cumulative share-based payment-related expenses recognized for accounting purposes should be recorded in shareholders’ equity rather than in current income tax expenses/benefits under U.S. GAAP.

Leasing

Under U.S. GAAP, as a lessee, the Company recognizes a lease liability based on the present value of the total remaining lease payments, and a corresponding right-of-use assets. The Company subsequently recognizes operating lease expenses on a straight-line basis over the lease term.

PRC GAAP requires lessees to present interest expenses on the lease liability and depreciation on the right-of-use assets separately in the statements of operations. The combination of a straight-line depreciation of the right-of-use assets and the effective interest rate method applied to the lease liability will result in a higher total charge to profit or loss in the initial years of the leases and decreasing expenses during the latter part of the lease term.

Gross Profit Margin Ratio

As required by the PRC Securities Laws, the 2024 STAR Annual Report contained financial information regarding gross profit margin ratio by region, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below. Amounts reported herein are stated in thousands of U.S. dollars.

For the year ended December 31, 2024
For the year ended December 31, 2023
By Region Revenue COGS Gross Margin ratio Revenue COGS Gross Margin ratio
China 1,411,307
524,220
62.9%
1,101,951 352,706 68.0%
Ex-China 2,398,934
69,869
97.1% 1,356,828 27,214 98.0%
Total 3,810,241 594,089 - 2,458,779 379,920 -

Research and Development Expenses Allocated by Key Products and Other R&D Projects

As required by the PRC Securities Laws, the 2024 STAR Annual Report contains financial information regarding the research and development ("R&D") expenses allocated by key products, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below. Amounts reported herein are stated in thousands of U.S. dollars.

Pipeline Products/ Projects
For the year ended December 31, 2024
For the year ended December 31, 2023
Zanubrutinib 129,226 158,051
Tislelizumab 68,684 83,799
Bcl-2 (BGB-11417) 99,939 52,548
CDAC (BGB-16673) 20,380 3,584
CDK4 (BGB-43395) 6,078 1,734
Other R&D projects 215,139 251,701
R&D collaboration projects 189,214 100,115
Subtotal of external R&D expenses 728,660 651,532
Subtotal of internal R&D expenses 1,224,635 1,127,062
Total 1,953,295 1,778,594

Production, Sales and Inventory Stock Units

As required by the PRC Securities Laws, the 2024 STAR Annual Report contained financial information regarding the production, sales and inventory stock units of key products, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below.

Item Unit
Production or purchase quantity for the year ended December 31, 2024
Sales quantity for the year ended December 31, 2024
Stock quantity as of December 31, 2024
Key products vials
5,011,100
5,037,600
2,639,900

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.