On April 28, 2025 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, reported new preclinical data in collaboration with Moderna on an mRNA encoded masked IL-12 molecule (Press release, CytomX Therapeutics, APR 28, 2025, View Source [SID1234652227]). The data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held in Chicago, IL on April 25-30, 2025.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to share new preclinical data at AACR (Free AACR Whitepaper), establishing proof of concept for an mRNA encoded masked molecule in the treatment of cancer," said Marcia Belvin, Ph.D. SVP, Chief Scientific Officer of CytomX Therapeutics. "IL-12 has shown promising anti-tumor activity, but its clinical use has been limited due to its inflammatory toxicity and narrow therapeutic window. By combining CytomX’s proprietary PROBODY masking technology and Moderna’s mRNA technology, we have created an mRNA therapeutic encoding a masked IL-12, designed to be selectively activated within the tumor microenvironment (TME), with limited systemic activity. The data presented at AACR (Free AACR Whitepaper) show proof of concept for this unique technology combination, a key initial goal of the CytomX-Moderna collaboration."

Details for the poster presentation are as follows:
Presentation Title: An mRNA-encoded masked IL-12 improves systemic tolerability while maintaining anti-tumor efficacy in preclinical studies
Poster Number: 3127/12
Section 24
Session Date and Time: April 28, 2025, 2:00 pm – 5:00 pm CT

On April 28, 2025 Crown Bioscience, a global contract research organization (CRO) headquartered in the United States and a part of JSR Life Sciences and Japan-based JSR Corporation, reported at AACR (Free AACR Whitepaper) 2025 its cutting-edge 3D bone marrow niche (BMN) in vitro models to advance hematological cancer research (Press release, Crown Bioscience, APR 28, 2025, View Source [SID1234652226]). Providing both the physical environment (cell-cell interactions), and the growth factor cocktail that hematological cancer cells require to thrive and proliferate, this innovative model provides a dynamic platform for studying liquid malignancies such as acute myeloid leukemia (AML) and multiple myeloma (MM).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The system incorporates key cellular components—stromal cells and endothelial cells—within biofunctional hydrogels seeded with patient-derived tumor cells, optionally supplemented with autologous immune cells. By accurately capturing the essential tumor microenvironment, the niche provides a physiologically relevant system that offers insight into tumor behavior, immune evasion, and drug resistance, outperforming classic suspension assays when it comes to cell viability, assay versatility, and clinical predictivity.

"Crown Bioscience is proud to unveil this high-content imaging-based 3D BMN platform that offers a unique and robust high-throughput drug screening in primary patient cells that allows testing of malignancies and toxicities at scale," said Ludovic Bourré, Vice President, Research and Innovation, Crown Bioscience. "Until now, bone marrow research has lagged behind solid tumor research due to lack of relevant in vitro models. With these BMN technological advances, we are now able to help researchers understand how cancer survives therapies once it reaches the bone marrow. This allows them to guide the selection of drug candidates with fewer off-target or bone marrow-related side effects and to overcome drug resistance mechanisms."

Researchers can realize significant benefits with the BMN models including:

The use of more predictive ex vivo data to increase accuracy in cancer cell response

The ability to screen compounds for hematological toxicity earlier in the drug development process

Enhanced translational insight for more informed in vivo studies, helping to reduce animal use and speed up drug development

Enabling the creation of more effective, targeted treatments through adhesion-mediated drug resistance modeling

Unlocking new potential in stem cell, hematological malignancy, and bone-marrow-specific oncology studies
The introduction of the BMN platform seamlessly integrates into Crown Bioscience’s expertise in 3D organoid-like cell cultures, drug resistance models, and AML mouse models and bridges a gap between in vitro and in vivo models.

Bourré said, "This is a very exciting advancement for researchers and with this offering that integrates into Crown Bioscience’s existing solutions, we’re able to continually foster innovation and accelerate drug development."

Crown Bioscience will be presenting a poster at AACR (Free AACR Whitepaper), with details below.

3D Bone Marrow Niche: Scalable and Physiologically Relevant Ex Vivo Drug Screening Platform for Acute Myeloid Leukemia and Multiple Myeloma
Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Discovery Assay Technologies
Session Date and Time: April 29 at 2:00PM CT
Location: Poster section 16
Poster Board Number: 21
Published Abstract Number: 5493

On April 28, 2025 Coherus BioSciences, Inc. ("Coherus," NASDAQ: CHRS), reported data from its ongoing Phase 1 clinical trial evaluating CHS-114, a selective, cytolytic anti-CCR8 antibody, as monotherapy and in combination with toripalimab in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) evaluating two pharmacologically active doses of CHS-114 for dose optimization (Press release, Coherus Biosciences, APR 28, 2025, View Source [SID1234652225]). These data are being presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25-30, 2025, in Chicago, Illinois.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The data showed a confirmed partial response in a heavily pretreated PD-1 refractory patient, a > 50% depletion in CCR8+ Treg, and an increase in CD8+ T cells, consistent with anti-tumor activity and demonstrating proof of mechanism. Importantly, the safety profile was consistent with advanced disease and the known safety profile of toripalimab. These data support continued evaluation of CHS-114 in combination with other therapies, including toripalimab. Results support advancement and ongoing enrolment in Part 3 of the study evaluating CHS-114 with toripalimab in HNSCC (n = 40).

CHS-114 is an afucosylated CCR8 monoclonal antibody and is the only known selective molecule designed to exclusively target human CCR8 with no off-target binding and preferentially kills CCR8+ Tregs within the tumor microenvironment while preserving CD8+ effector T cells and Tregs in normal tissue.

"The data to date demonstrate a robust depletion of Treg cells in tumors, with a manageable safety profile, and a patient with a meaningful clinical response, which is highly encouraging," said Rosh Dias, M.D., Coherus’ Chief Medical Officer. "Furthermore, the profound increase in CD8+ T cells, making these tumors immunologically hot, is exciting as it supports CHS-114 being combined with several treatment modalities including T Cell Engagers. Head and neck cancer is an important strategic focus for Coherus, but CHS-114 has the potential, based on its mechanism of action, to treat many solid tumors, including non-small cell lung cancer and other large, underserved immuno-oncology indications, like colorectal cancer. We look forward to sharing further head and neck and gastric cancer data in the first half of next year."

"One of the biggest challenges in oncology has been finding a treatment that depletes Treg cells and relieves immune suppression in the tumor without causing collateral autoimmune disease or affecting antitumor T cells," said Douglas Adkins, M.D., Professor of Medicine, Director, Section of Head and Neck and Thyroid Medical Oncology, Division of Medical Oncology, Washington University School of Medicine. "These early clinical results are exactly what we’ve been hoping for and demonstrate CHS-114’s ability to remodel the tumor microenvironment in favor of anti-tumor activity. I am looking forward to exploring this treatment combination for solid tumor patients, even beyond head and neck."

Results from Phase 1b dose expansion trial evaluating CHS-114 monotherapy and with toripalimab in HNSCC

This open-label Phase 1b clinical trial evaluated CHS-114 as a single-agent and in combination with toripalimab in 21 patients with advanced solid tumors including HNSCC. Patients received either CHS-114 alone or in combination with toripalimab (240 mg) q3w. The primary endpoint of the study was to determine dose limiting toxicities (DLTs) and treatment emergent adverse events (TEAEs), with the goal of identifying two recommended doses for expansion. Key secondary endpoints included objective response rate (ORR) based on investigator review per RECIST v1.1 as well as pharmacokinetics and pharmacodynamics (PK/PD).

As of the data cutoff date of January 24, 2025:

CHS-114 monotherapy demonstrated Treg cell depletion (range of decrease: 52-97%), and significant increase in CD8+ T cells in the tumor, establishing proof of mechanism and confirming the doses are pharmacologically active.
CHS-114 with toripalimab had promising antitumor activity in HNSCC that warrants continued exploration.
CHS-114 administration leads to a substantial increase in CD8+ T cells in the tumor microenvironment, providing a strong rationale for combining with toripalimab and other drugs such as T cell engagers and bispecifics.
A confirmed partial response was achieved in the high dose cohort of CHS-114 in combination with toripalimab in a heavily pre-treated PD-1 refractory patient (PD-L1 low), demonstrating CHS-114 in combination with toripalimab can potentially overcome PD-1 resistance.
CHS-114 with and without toripalimab had a manageable safety profile in HNSCC patients, with TEAEs consistent with advanced disease and the known safety profile of toripalimab.
Two CHS-114 doses were selected for dose optimization based on safety, peripheral CCR8+ Treg depletion, PK and biomarker data.
These results support continued evaluation of CHS-114 in combination with other drugs including toripalimab, with broad potential applications in many solid tumors with a high density of CCR8+ Treg cells. A second-line HNSCC dose optimization study of CHS-114 in combination with toripalimab in HNSCC and gastric cancer patients is ongoing, with anticipated results in the first half of 2026 The current study design is expected to address the regulatory requirements under Project Optimus1 and support the recommendation of a phase 2 dose by early 2026.

AACR 2025 Presentation Details

Title: Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors
Lead Author: Francis Worden, M.D., University of Michigan
Abstract #: CT038
Poster Session: Phase 0 and Phase 1 Clinical Trials
Poster Section 49: Poster board 17
Date and Time: Monday, April 28, 2025, 9:00 a.m. – 12:00 p.m. CDT

Conference Call Information for Investors and Analysts

Coherus Chief Development Officer, Dr. Theresa LaVallee, and Chief Medical Officer, Dr. Rosh Dias, will host a presentation and discussion of new clinical data from the Phase 1 study with CHS-114 with and without anti-PD-1 antibody toripalimab with study investigator, Dr. Douglas Adkins of Washington University.

When: Monday, April 28, 2025, starting at 4:30 p.m. Eastern Time

Investors and analysts are invited to listen into a live audio webcast of the presentation. To access the conference call, please pre-register through the following link to receive dial-in information and a personal PIN to access the live call: View Source

Please dial in 15 minutes early to ensure a timely connection to the call.

Webcast: View Source

An archived webcast will be available on the "Investors" section of the Coherus website at View Source

About the CHS-114 Phase 1 Study

The Phase 1 study (NCT05635643) is a dose escalation, dose optimization, and expansion study evaluating CHS-114 as a monotherapy and in combination with toripalimab, a next-generation PD-1 inhibitor. Arm 1a (first-in-human dose escalation) enrolled 20 patients with advanced solid tumors including 2 patients with HNSCC and evaluated multiple dose levels (5-1200 mg) of CHS-114 monotherapy. Arm 1b evaluated two pharmacologically active doses of CHS-114 monotherapy in 12 HNSCC patients with paired tumor biopsies. Arm 2 evaluated two pharmacologically active doses of CHS-114 with toripalimab in 7 patients. Arm 3 is evaluating two pharmacologically active doses of CHS-114 with toripalimab in 40 patients with second-line HNSCC. Primary objectives are to optimize the CHS-114 dose(s) for expansion and evaluate the safety of CHS-114 with toripalimab. Secondary objectives were to evaluate the safety, PK, and antitumor activity of CHS-114 with and without toripalimab and assess biomarkers, including changes in regulatory T cells (Tregs) and CD8+ T cells in paired tumor biopsies and other immune biomarkers.

About CHS-114

CHS-114, an afucosylated, cytolytic CCR8 monoclonal antibody, is designed to selectively target human CCR8 and preferentially kill CCR8+ Tregs within the tumor microenvironment while preserving CD8+ effector T cells and Tregs in normal tissue. In preclinical studies, CHS-114 induced antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) to deplete tumoral CCR8+ Tregs. In addition, treatment with CHS-114 alone reduced tumor growth in murine models, and enhanced antitumor activity was observed in combination with anti-PD-1 treatment. CHS-114 is currently being evaluated in combination with toripalimab in two Phase 1b clinical trials in patients with advanced solid tumors, including head and neck cancer (NCT05635643) and gastric cancer (NCT06657144).

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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