On October 13, 2025 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported it will jointly present a poster on translational data and updated clinical results from the Phase I study of BT-001 at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting. ESMO (Free ESMO Whitepaper) will take place in Berlin, Germany, from October 17 to 21, 2025 (Press release, Transgene, OCT 13, 2025, View Source [SID1234656590]).

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Key findings of the abstract include:

– Intra-tumoral (IT) BT-001 injection in combination with intravenous (IV) pembrolizumab was well tolerated with a manageable safety profile.

– The data show encouraging and sustained anti-tumor activity in patients with advanced refractory tumors. One patient with PD(L)-1 resistant melanoma and one patient with heavily pretreated and Immune Checkpoint Inhibitor (ICI)-naive leiomyosarcoma showed partial response (iPR) lasting 6 and 16 months respectively, among the 13 patients who received the combination of IT BT-001 (at 107 pfu/mL and 108 pfu/mL) and IV pembrolizumab.

– Tumor shrinkage was observed in both injected and non-injected lesions.

– BT-001 could be an effective option to improve the response to ICI in refractory patients.

The abstract is available on the ESMO (Free ESMO Whitepaper) website (here). The poster will be presented on October 20 during ESMO (Free ESMO Whitepaper) 2025 and will also be available to view on Transgene’s website.

BT-001 is an oncolytic virus generated using Transgene’s Invir.IO platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting recombinant human anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine.

BT-001 is being co-developed as part of a 50/50 collaboration between Transgene and BioInvent. In the Phase I part of this study, BT-001 was well tolerated both as monotherapy and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab)*.

The Phase I/IIa study (NCT04725331) is a multicenter, open label, dose-escalation study evaluating BT-001 as a single agent and in combination with pembrolizumab*. The last patient in the Phase I part was enrolled in August 2024.

Treatment with BT-001 converted "cold" tumors into "hot" ones, and induced T-cell infiltration, as well as PD(L)-1 expression in the tumor microenvironment (ESMO 2024, access press release here).

*KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On October 13, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that a late-breaking abstract (LBA) featuring new data from its global Phase 1 clinical trial (NCT06179069) evaluating zocilurtatug pelitecan (zoci), formerly known as ZL-1310, has been selected for an oral presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place October 22-26, 2025, in Boston, Massachusetts (Press release, Zai Laboratory, OCT 13, 2025, View Source [SID1234656606]). The presentation will include additional follow-up from patients from the ongoing trial.

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Zoci is the Company’s potential first- and best-in-class, Delta-like ligand (DLL3)-targeted antibody-drug conjugate (ADC) being developed for patients with extensive-stage small cell lung cancer (ES-SCLC). The ongoing Phase 1 study is evaluating the safety and antitumor activity of zoci at various doses in patients who have progressed after at least one prior platinum-based chemotherapy regimen. The study is being conducted across multiple global sites.

"The critical need for expanded treatment options for patients with small cell lung cancer propels our strategy to advance zoci as a novel therapeutic option as quickly as possible," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "We remain on track to initiate our Phase 3 registrational study in previously treated SCLC by year-end. We look forward to sharing updated results demonstrating zoci’s continued potential at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference."

Zai Lab will hold an investor conference call and webcast to highlight updated zoci data at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference and outline next steps in clinical development.

Details regarding the webcast and conference call are as follows:

Date/Time: October 24, 2025, at 11 a.m. ET / 11 p.m. HKT, please register at:
Webcast presentation (preferred): View Source
Dial-in: View Source
Presenter: Rafael G. Amado, M.D., President and Head of Global Research and Development, Zai Lab

Details regarding the zoci oral presentation are as follows:

Title: Phase 1 trial of ZL-1310, a DLL3-targeted ADC, in patients with previously treated extensive-stage small cell lung cancer
Presenter: Grace K. Dy, M.D., Roswell Park Comprehensive Cancer Center, Buffalo, NY
Session Title: Plenary Session 3: Antibody Drug Conjugates
Date/Time: Friday, October 24, 2025, 9:17 a.m. – 9:27 a.m. ET (presentation), 9:27 a.m. – 9:45 a.m. ET (panel discussion)
Location: Hynes Convention Center, Level 3, Ballroom AB

About Small Cell Lung Cancer and Zocilurtatug Pelitecan (zoci)

Small cell lung cancer (SCLC) is one of the most aggressive and lethal solid tumors, accounting for ~15% of the approximately 2.5 million patients diagnosed with lung cancer worldwide each year1,2. Additionally, two-thirds of all SCLC patients are diagnosed at extensive stage3.

DLL3 is an antigen overexpressed in many neuroendocrine tumors, such as SCLC, and is often associated with poor clinical outcomes. Zocilurtatug pelitecan (zoci), formerly known as ZL-1310, comprises a humanized anti-DLL3 monoclonal antibody connected via a cleavable linker to a novel camptothecin derivative (a topoisomerase 1 inhibitor) as its payload. The compound was designed with a novel ADC technology platform called TMALIN, which leverages the tumor microenvironment to overcome challenges associated with first-generation ADC therapies.

Zoci received an Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in January 2025, recognizing its potential to treat patients with SCLC.

About the Webcast and Conference Call

All participants must use the link provided above to complete the online registration process in advance of the conference call. Dial-in details will be in the confirmation email which the participant will receive upon registering.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website.

On October 13, 2025 Daiichi Sankyo reported data at ESMO (Free ESMO Whitepaper) will spotlight the company’s advances towards creating new standards of care for patients with breast cancer, including back-to-back presentations during Presidential Symposium I featuring data from the DESTINY-Breast11 (291O) and DESTINY-Breast05 (LBA1) phase 3 trials (Press release, Daiichi Sankyo, OCT 13, 2025, https://daiichisankyo.us/press-releases/-/article/daiichi-sankyo-continues-to-transform-standards-of-care-for-patients-with-three-landmark-breast-cancer-trials-and-additional-data-across-industry-leading-adc-portfolio-at-esmo [SID1234656591]). Results of these two landmark trials will showcase the potential of ENHERTU (trastuzumab deruxtecan) to become a foundational treatment in curative-intent settings of HER2 positive early breast cancer.

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Late-breaking DATROWAY (datopotamab deruxtecan) data from the TROPION-Breast02 phase 3 trial (LBA21), representing the first trial ever to demonstrate a significant improvement in overall survival compared to chemotherapy as first-line treatment for patients with locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) for whom immunotherapy is not an option, will be featured in a proffered paper session.

"Data from these three landmark trials demonstrate how the DXd ADC portfolio of Daiichi Sankyo continues to transform standards of care for patients with breast cancer. The findings from DESTINY-Breast11 and DESTINY-Breast05 highlight the potential of ENHERTU to become a foundational treatment in the curative-intent settings of HER2 positive early breast cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Additionally, the DATROWAY results from TROPION-Breast02 represent the first time ever that an overall survival benefit has been demonstrated in the first-line setting of patients with metastatic triple negative breast cancer for whom immunotherapy is not an option. Couple these impressive results for DATROWAY with previous results seen with ENHERTU in the HER2 positive, HER2 low and HER2 ultralow disease settings, Daiichi Sankyo will now have two medicines with the potential to treat approximately 90 percent of patients with metastatic breast cancer."

Additional breast cancer data at ESMO (Free ESMO Whitepaper) includes a mini oral presentation of data from Arm 7 and Arm 8 of the BEGONIA phase 1/2 trial (555MO) evaluating DATROWAY plus durvalumab in patients with first-line metastatic TNBC. The efficacy and safety of this combination strategy is being further investigated in three phase 3 trials – TROPION-Breast03, TROPION-Breast04 and TROPION-Breast05 – across stages and treatment settings of TNBC.

Trials Supporting Three Recent Breakthrough Therapy Designations Showcased
Data from additional late-stage trials – DESTINY-Breast09, REJOICE-Ovarian01 and IDeate-Lung01 – that supported three recent Breakthrough Therapy Designations (BTD) in the U.S. for ENHERTU, raludotatug deruxtecan (R-DXd) and ifinatamab deruxtecan (I-DXd) will be showcased at ESMO (Free ESMO Whitepaper).

Two late-breaking proffered paper sessions will highlight the primary analysis from the phase 2 part of the REJOICE-Ovarian01 phase 2/3 trial (LBA42) of raludotatug deruxtecan in patients with previously treated platinum-resistant ovarian cancer, and additional analyses of key subgroups of interest from the DESTINY-Breast09 phase 3 trial (LBA18) evaluating ENHERTU plus pertuzumab versus THP (taxane, trastuzumab, pertuzumab) for the first-line treatment of patients with HER2 positive metastatic breast cancer. Results of DESTINY-Breast09 formed the basis for a supplemental Biologic License Application in the U.S. for ENHERTU, which was recently granted Priority Review under the Real-Time Oncology Review program.

Detailed results highlighting the intracranial activity of ifinatamab deruxtecan from the IDeate-Lung01 phase 2 trial (2760MO) in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC) and baseline brain metastases will be highlighted during a mini oral session. The primary results of IDeate-Lung01 were presented last month at the 2025 World Conference on Lung Cancer (#WCLC25).

Progress Continues in Multiple Cancers Across the DXd ADC Portfolio of Daiichi Sankyo
Additional mini oral sessions at ESMO (Free ESMO Whitepaper) will feature the first presentation of data from two early phase trials from the DXd ADC portfolio of Daiichi Sankyo. These include preliminary results from the first-in-human phase 1/2 trial of DS-3939 (917O), the sixth DXd ADC in clinical development, in patients with previously treated advanced solid tumors refractory to standard treatment, as well as initial results from a sub-study of the TROPION-PanTumor03 phase 2 trial (3072MO) evaluating DATROWAY plus rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, in patients as first-line or second-line locally advanced or metastatic urothelial carcinoma.

Final analyses from two trials – DESTINY-CRC02 and DESTINY-PanTumor02 – that supported the tumor agnostic indication of ENHERTU, which is now approved in more than 10 countries/regions worldwide, will be presented. A mini oral session will feature the final analysis from the DESTINY-CRC02 phase 2 trial (737MO) of ENHERTU in patients with previously treated HER2 positive metastatic colorectal cancer while two poster presentations will highlight the final results (957P) and an exploratory biomarker analysis (145P) from part 1 of the DESTINY-PanTumor02 phase 2 trial in patients with previously treated HER2 expressing solid tumors. Additional regulatory submissions seeking a tumor agnostic approval in patients with HER2 positive metastatic solid tumors currently are under review in the EU and Japan.

Further sub-analyses from the DESTINY-Gastric04 phase 3 trial of ENHERTU versus ramucirumab plus paclitaxel in the second-line treatment of patients with HER2 positive metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma will be presented as a poster presentation (2099P) reporting the concordance of central HER2 testing with local HER2 testing along with additional efficacy and safety analyses. Data from DESTINY-Gastric06, a phase 2 trial in patients from China with HER2 expressing advanced gastric or GEJ adenocarcinoma who have received at least two prior regimens including a fluoropyrimidine agent and a platinum agent, will be presented in two poster presentations. The first poster (2105P) will feature an analysis of patients that received prior anti-HER2 treatment other than or in addition to trastuzumab. The second poster (2175P) will report the risk of hepatitis B virus reactivation in patients with past or resolved HBV or inactive chronic HBV infection treated with ENHERTU.

Updates of progress in lung cancer include a mini oral session reporting updated results from a phase 1/2 trial of gocatamig (2758MO), a DLL3 targeting T-cell engager being jointly developed by Merck, in patients with small cell lung cancer and other neuroendocrine cancers, as well as a poster presentation that will highlight the initial safety results from a phase 1b trial of valemetostat (2023P), a dual EZH1 and EZH2 inhibitor, in combination with DATROWAY in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC).

Trials-in-Progress Across Daiichi Sankyo’s Oncology Portfolio
Several trials-in-progress poster presentations at ESMO (Free ESMO Whitepaper) further highlight the Daiichi Sankyo R&D strategy of continuing to expand the DXd ADC portfolio to address a broad spectrum of unmet needs for patients with cancer.

A trial-in-progress poster will highlight the design of the DESTINY-Endometrial01 phase 3 trial (1223TiP) evaluating ENHERTU in combination with rilvegostomig or pembrolizumab versus platinum-based chemotherapy (carboplatin and paclitaxel) in combination with pembrolizumab as a first-line therapy in patients with HER2 expressing (IHC 3+/ 2+), mismatch repair proficient (pMMR) primary advanced or recurrent endometrial cancer.

Three phase 2 trials-in-progress will include the HERTHENA-Breast03 trial (463eTiP) evaluating neoadjuvant patritumab deruxtecan (HER3-DXd) plus pembrolizumab before or after pembrolizumab plus chemotherapy in patients with high-risk early-stage TNBC or HR low positive/HER2 negative breast cancer; the REJOICE-GI01 trial (1001TiP) evaluating the efficacy and safety of raludotatug deruxtecan in patients with gastrointestinal cancers, including pancreatic ductal adenocarcinoma, gastroesophageal adenocarcinoma, biliary tract and colorectal cancer; and, the KEYMAKER-U01 sub-studies 01H/01I (2081eTiP) evaluating ifinatamab deruxtecan, raludotatug deruxtecan or docetaxel in patients with stage IV NSCLC.

The design of two additional early phase trials will be shared, including the phase 1/2 trial (2792TiP) evaluating ifinatamab deruxtecan and gocatamig in patients with relapsed/refractory ES-SCLC and a phase 1b trial (977P) of valemetostat in combination with ipilimumab in patients with refractory genitourinary tumors, including prostate cancer, urothelial carcinomas and renal clear cell carcinoma.

Investor Briefing During ESMO (Free ESMO Whitepaper)
Daiichi Sankyo will hold a virtual conference call for investors on Tuesday, October 21, 2025 from 8:00 to 9:30 am EDT / 9:00 to 10:30 pm JST. Executives from Daiichi Sankyo will provide an overview of the ESMO (Free ESMO Whitepaper) data.

Daiichi Sankyo Oral Presentations at ESMO (Free ESMO Whitepaper)

Presentation Title

Author

Abstract

Presentation (CEST)

Breast

Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with high-risk human epidermal growth factor receptor 2-positive (HER2+) primary breast cancer with residual invasive disease after neoadjuvant therapy: interim analysis of DESTINY-Breast05

C. Geyer

LBA1

Presidential Symposium I

Saturday, October 18

4:30 – 6:15 pm

DESTINY-Breast11: neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer

N. Harbeck

291O

Presidential Symposium I

Saturday, October 18

4:30 – 6:15 pm

Trastuzumab deruxtecan (T-DXd) + pertuzumab vs taxane + trastuzumab + pertuzumab (THP) for patients with HER2+ advanced/metastatic breast cancer: additional analyses of DESTINY-Breast09 in key subgroups of interest

S. Loibl

LBA18

Proffered Paper Session

Sunday, October 19

8:30 – 10:00 am

First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple negative breast cancer for whom immunotherapy was not an option: primary results from the randomized, phase 3 TROPION-Breast02 trial

R. Dent

LBA21

Proffered Paper Session

Sunday, October 19

8:30 – 10:00 am

Datopotamab deruxtecan (Dato-DXd) + durvalumab as first-line treatment for unresectable locally advanced/ metastatic triple negative breast cancer: final results from the phase 1b/2 BEGONIA study

P. Schmid

555MO

Mini Oral Session

Monday, October 20

10:15 – 11:45 am

Lung

Intracranial activity of ifinatamab deruxtecan (I-DXd) in patients with extensive-stage small cell lung cancer and baseline brain metastases: primary analysis of IDeate-Lung01

P. Rocha

2760MO

Mini Oral Session

Saturday, October 18

4:30 – 6:00 pm

Updated results from a phase 1/2 study of gocatamig for small cell lung cancer and other neuroendocrine cancers

H. Beltran

2758MO

Mini Oral Session

Saturday, October 18

4:30 – 6:00 pm

Ovarian

Raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer: primary analysis of the phase 2 dose- optimization part of the REJOICE-Ovarian01 study

I. Ray-Coquard

LBA42

Proffered Paper Session

Sunday, October 19

2:45 – 4:15 pm

Bladder

Datopotamab deruxtecan (Dato-DXd) + rilvegostomig in patients with locally advanced or metastatic urothelial cancer: results from the phase 2 TROPION-PanTumor03 study

S. Rha

3072MO

Mini Oral Session

Friday, October 17

4:00 – 5:30 pm

CRC

Trastuzumab deruxtecan (T‑DXd) in patients with HER2 positive (HER2+) metastatic colorectal cancer: final analysis of DESTINY-CRC02, a randomized, phase 2 trial

K. Raghav

737MO

Mini Oral Session

Sunday, October 19

2:45 – 4:15 pm

PanTumor

DS-3939, a tumor-associated mucin 1 (TA-MUC1)-directed antibody drug conjugate (ADC), in patients with advanced/metastatic solid tumors: initial results from a first-in-human study

M. Patel

917O

Proffered Paper Session

Sunday, October 19

2:45 – 4:20 pm

Daiichi Sankyo Poster Presentations at ESMO (Free ESMO Whitepaper)

Presentation Title

Author

Abstract

Presentation (CDT)

Breast

Final real-world safety and effectiveness results of REALITY-01 study: trastuzumab deruxtecan (T-DXd) in patients received ≥2 prior treatment lines for HER2+ metastatic or unresectable breast cancer

J. Pierga

539P

Poster Session

The effectiveness of post-trastuzumab deruxtecan (T-DXd) treatment regimens and the incidence of recurrent interstitial lung disease (ILD) in patients with HER2+ metastatic breast cancer who discontinued T-DXd due to ILD

J. Tsurutani

540P

Poster Session

HERTHENA-Breast03: a phase 2, randomized, open-label study evaluating neoadjuvant patritumab deruxtecan + pembrolizumab before or after pembrolizumab + chemotherapy for early-stage TNBC or HR low+/HER2− breast cancer

M. Danso

463eTiP

ePoster

Lung

Phase 1b study of valemetostat in combination with datopotamab deruxtecan (Dato-DXd) in advanced non-squamous non-small cell lung cancer: initial safety results

A. Spira

2023P

Poster Session

A phase 1b/2 study of gocatamig (MK-6070; HPN328) and ifinatamab deruxtecan for relapsed/refractory extensive-stage small cell lung cancer

J. Sun

2792TiP

Poster Session

KEYMAKER-U01 phase 2 substudies 01H/01I: ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) or docetaxel in stage IV non-small cell lung cancer

E. Nadal

2081eTiP

ePoster

Gastrointestinal

Trastuzumab deruxtecan (T-DXd) vs ramucirumab plus paclitaxel in second-line treatment of patients with HER2+ unresectable/metastatic gastric cancer/gastroesophageal junction adenocarcinoma: additional data from DESTINY-Gastric04

F. Pietrantonio

2099P

Poster Session

Trastuzumab deruxtecan (T-DXd) in patients with HER2+ gastric cancer or gastroesophageal junction adenocarcinoma who received prior anti-HER2 treatment other than/in addition to trastuzumab in DESTINY-Gastric06

Z. Peng

2105P

Poster Session

Risk of hepatitis B virus reactivation in patients with past or resolved HBV or inactive chronic HBV infection treated with trastuzumab deruxtecan (T-DXd) in the DESTINY-Gastric06

L. Shen

2175P

Poster Session

Raludotatug deruxtecan in participants with gastrointestinal cancers: phase 2 REJOICE-GI01 trial

M. Ueno

1001TiP

Poster Session

Endometrial

A randomized phase 3 study of first-line trastuzumab deruxtecan (T-DXd) with rilvegostomig or pembrolizumab in patients with HER2 expressing, mismatch repair-proficient, primary advanced or recurrent endometrial cancer: DESTINY-Endometrial01/GOG-3098/ENGOT-EN24

B. Slomovitz

1223TiP

Poster Session

PanTumor

Trastuzumab deruxtecan (T-DXd) for pretreated patients with HER2 expressing solid tumors: DESTINY-PanTumor02 part 1 final analysis

V. Makker

957P

Poster Session

Trastuzumab deruxtecan (T-DXd) in pretreated patients with HER2 expressing solid tumors: exploratory biomarker analysis of DESTINY-PanTumor02 part 1

D. Oh

145P

Poster Session

DS3201 (valemetostat), an EZH1/2 inhibitor, with ipilimumab in patients with refractory genitourinary tumors

S. Goswami

977P

Poster Session

On October 13, 2025 Children’s Hospital Los Angeles reported a groundbreaking study led by researchers that offers critical insights into Ewing Sarcoma, a rare and aggressive bone and soft tissue cancer that primarily affects children and adolescents (Press release, Children’s Hospital Los Angeles, OCT 13, 2025, View Source [SID1234656607]).

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The study, a close collaboration with the Keck School of Medicine of USC, provides the first in vivo genetic evidence that Ewing sarcoma may originate from neural crest cells—flexible embryonic cells that normally give rise to neurons, glial cells, and pigment cells.

For decades, scientists have been puzzled by two enduring mysteries around Ewing sarcoma. Why does this aggressive bone and soft tissue cancer mainly affect children and adolescents? And why do its tumor cells appear so primitive, showing features of multiple different cell types?

The team showed that a common mutation in this cancer—the EWSR1::FLI1 fusion oncogene—can reprogram neural crest cells into a mesoderm-like state, adopting features of bone- and muscle-forming cells. Results were published in Cell Reports.

"This is an exciting step forward in Ewing sarcoma research," says James Amatruda, MD, PhD, Director of the Cancer and Blood Disease Institute at Children’s Hospital Los Angeles and senior author of the study. "By understanding where and how this disease begins, we open the door to developing more effective and less-toxic treatments."

Scientists have known for more than 30 years that the EWSR1::FLI1 fusion is the driver of Ewing sarcoma. But they didn’t know which specific cells it could transform into cancer, and they lacked reliable research models of the disease. Those gaps have stalled progress in finding new and better therapies.

To study this cancer’s earliest steps, Dr. Amatruda’s lab published the first genetic zebrafish model of Ewing sarcoma in 2022. Zebrafish embryos are transparent and develop outside the mother, allowing the team to characterize the earliest stages of Ewing sarcoma and track fluorescently tagged tumor cells in real time.

In this latest study, researchers used the zebrafish model to switch on the EWSR1::FLI1 fusion in different cell types. Most cells died. But neural crest cells were the exception. They not only survived, but they were reprogrammed into a mesoderm-like state, setting the stage for tumor initiation.

The work was the result of a collaboration between Dr. Amatruda’s team at CHLA and the laboratory of Gage Crump, PhD, Professor and Vice Chair of Stem Cell Biology and Regenerative Medicine at USC. Elena Vasileva, PhD, a postdoctoral fellow at CHLA, was the study’s first author.

The team found that the oncogene doesn’t just push cells down the wrong path—it co-opts the same signaling pathways the cells use in normal development. This forces the neural crest cells into an "in-between" state that fuels uncontrolled growth.

"It was remarkable to see how these pre-tumor cells changed their behavior and characteristics, contributing to tumor development later on," Dr. Vasileva says. "Even more surprising was that the reprogrammed cells appeared to hijack normal developmental programs, such as those responsible for limb development."

Because neural crest cells are only present during early development, the findings help explain why Ewing sarcoma affects children and adolescents, but not older adults. The cells’ reprogramming may also account for the puzzling mixed appearance of Ewing sarcoma cells under the microscope.

"The precancer cells seem to be caught at a crossroads of multiple potential cell fate decisions," Dr. Vasileva explains. "By understanding these reprogramming trajectories, we may be able to uncover new vulnerabilities of cancer cells and identify new therapeutic targets."

Next steps for Ewing sarcoma research

By pinpointing a likely cell of origin for Ewing sarcoma, the researchers can now explore new questions: How do these reprogrammed cells fuel tumor growth? What signals do they hijack to spread? And how might those processes be stopped?

The zebrafish model gives the team a powerful tool to study how tumor cells evade the immune system and why they metastasize so aggressively. Researchers are also investigating how these cancer cells interact with their surrounding microenvironment—the network of cells and proteins that tumors hijack to survive.

"The more we understand about how Ewing sarcoma begins, the better models we can build to accurately mimic the disease," Dr. Amatruda says. "The ultimate goal is to find new and less-toxic treatments for this cancer—and improve outcomes for children."

On October 13, 2025 Alligator Bioscience (Nasdaq Stockholm: ATORX), a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs, reported the upcoming presentation of data from the Phase 1 REACtiVe-2 trial (NCT05650918) at the ESMO (Free ESMO Whitepaper) Congress 2025, showcasing the immunologic and clinical effects of mitazalimab in combination with dendritic cell therapy in patients with metastatic pancreatic cancer (Press release, Alligator Bioscience, OCT 13, 2025, View Source [SID1234656575]).

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The investigator-sponsored trial, conducted at Erasmus MC Cancer Institute, demonstrated that the combination of mitazalimab and Amphera’s dendritic cell vaccine MesoPher was safe and well-tolerated, with enhanced systemic and local immune responses. Half of the patients achieved stable disease after three administrations, with post-treatment biopsies revealing increased tumor-infiltrating T cells and reduced collagen deposition.

Title: REACtiVe-2: Phase I Evaluation of Dendritic Cell Vaccination and Agonistic CD40 Therapy Following (m)FOLFIRINOX in Metastatic Pancreatic Cancer
Presentation number: 2218P
Date and time: Sunday, 19 October, 12 p.m.-12:45 p.m. CEST.

"These clinical data clearly demonstrate the immune-stimulatory capacity of mitazalimab in patients with pancreatic cancer. They provide important mechanistic support for mitazalimab’s mode of action as a tumor-directed CD40 agonist," said Søren Bregenholt, CEO of Alligator Bioscience. "As we actively pursue out-licensing opportunities, results such as these reinforce mitazalimab’s value proposition in immuno-oncology and its potential in novel combination therapies."