On March 17, 2025 EsoBiotec SA, a biotechnology company pioneering in vivo cell therapies that has demonstrated promising early clinical activity, reported it has entered into a definitive agreement to be acquired by AstraZeneca (Press release, EsoBiotec, MAR 17, 2025, View Source [SID1234651164]). The EsoBiotec Engineered NanoBody Lentiviral (ENaBL) platform empowers the immune system to attack cancers and could offer many more patients access to transformative cell therapy treatments delivered in just minutes rather than the current process which takes weeks.

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ENaBL uses highly targeted lentiviruses to deliver genetic instructions to specific immune cells, such as T cells, which programme them to recognise and destroy tumour cells for cancer treatment or autoreactive cells for potential use in immune-mediated diseases. This approach enables cell therapies to be administered through a simple IV injection and without the need for immune cell depletion.

Traditional cell therapies require cells to be removed from a patient, genetically modified outside the body, and then readministered to the patient as a medicine after immune cell depletion, typically taking weeks. By engineering immune cells directly within the patient’s body, the EsoBiotec in vivo approach has the potential to address many of the barriers associated with traditional cell therapies, reducing complexities and manufacturing timelines, thereby increasing access for patients.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "We are excited about the acquisition of EsoBiotec and the opportunity to rapidly advance their promising in vivo platform. We believe it has the potential to transform cell therapy and will enable us to scale these innovative treatments so that many more patients around the world can access them. EsoBiotec will accelerate and expand the impact of our recent investments and marks a major step forward in realising our ambition to harness the full potential of cell therapy."

Jean-Pierre Latere, PhD, CEO, EsoBiotec, said: "We look forward to working with AstraZeneca, a global leader in drug development, to advance our shared goal of bringing transformative cost-effective cell therapies to more patients globally. By combining our expertise and resources, we can accelerate the development of our in vivo platform which has a novel delivery technology we believe will have broad therapeutic applicability."

EsoBiotec will become a wholly owned subsidiary of AstraZeneca, with operations in Belgium.

Financial considerations
AstraZeneca will acquire all outstanding equity of EsoBiotec for a total consideration of up to $1,000m, on a cash and debt free basis. This will include an initial payment of $425m on deal closing, and up to $575m in contingent consideration based on development and regulatory milestones.

The transaction is expected to close in the second quarter of 2025, subject to customary closing conditions and regulatory clearances.

Centerview Partners UK LLP is acting as exclusive financial advisor to EsoBiotec.

Cooley LLP is acting as legal advisor to EsoBiotec. Covington & Burling LLP is acting as legal advisor to AstraZeneca.

On March 16, 2025 Limula, a life science tools company specializing in automated Cell and Gene Therapy manufacturing solutions, reported the publication of a peer reviewed article in Cell Press journal Molecular Therapy – Methods & Clinical Development (Press release, Limula, MAR 16, 2025, View Source [SID1234651227]). Entitled Magnetic bead-sensitized optoporation coupled with antibodies-based activation for mRNA CAR-T cell manufacturing, the report describes the development of an innovative method for non-viral gene transfer. It is the result of a long-standing collaboration between the Limula team and Prof. Denis Migliorini from the University of Geneva.

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The introduction of synthetic genetic material into human primary cells is a key step in the production of CAR-T cells and other advanced therapy medicinal products (ATMPs). The vast majority of approved ATMPs rely on stable genetic modifications of patients’ cells using viruses that randomly integrate an exogenous sequence into the genome. More recently, therapies that rely on electroporation have also received marketing authorisation.

The innovative approach proposed by Limula and their collaborators is based on optoporation, a method that uses high-intensity laser to tigger transient permeabilization of the cell membrane. The resulting tiny holes allow molecular payloads, such as mRNA or CRISPR proteins, to enter the cells. The effect was previously shown to be ehanced by the addition of photosensitizers that efficiently absorb light and convert the energy into different phenomena that generate holes in the cell membrane.

Harnessing light for intracellular cargo delivery is not entirely new. Although optoporation using gold nanoparticles has demonstrated potential in the past, the work described in the scientific article demonstrates for the first time that the process can be efficiently catalysed by magnetic particles routinely used in cell therapy manufacturing.

The main contributor to the study, Dr. Noelia Maldonado-Pérez, says: "It is very satisfying to share the outcome of this project with the broader cell therapy community. The discovery that common cell activation reagents could be repurposed to catalyse the introduction of genetic material into human cells is very exciting."

Cell activation is one of the critical steps of CAR-T cell therapy manufacturing, often immediately followed by a gene transfer step. Some challenges remain in the application of the method to the production of clinical-grade advanced therapy products, but the possibility to sequence two different unit operations without the need for additional reagents could open avenues for streamlined production methods.

Prof. Denis Migliorini adds: "We believe magnetic bead-sensitized optoporation represents an interesting addition to the toolbox available to cell therapy developers."

On March 16, 2025 Akeso Inc. (9926.HK) reported that its innovative, self-developed anti-PD-1 monoclonal antibody, penpulimab, has been officially approved by the National Medical Products Administration (NMPA) for the first-line treatment of recurrent or metastatic nasopharyngeal cancer (NPC) in combination with chemotherapy (Press release, Akeso Biopharma, MAR 16, 2025, View Source [SID1234651161]).

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Previously, penpulimab was approved for use as a third-line treatment for advanced NPC. With this new approval, penpulimab now provides comprehensive treatment coverage across all stages of NPC, offering patients a continuous immunotherapy option from first-line to third-line therapy.

This marks the fourth approved indication for penpulimab. In addition to the two NPC indications, penpulimab is also approved for first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) when combined with chemotherapy, as well as for monotherapy in patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have previously received at least two lines of systemic chemotherapy. Furthermore, a supplemental New Drug Application (sNDA) for penpulimab in combination with anlotinib for first-line treatment of advanced hepatocellular carcinoma (HCC) is currently under review.

Professor Hu Chaosu, one of the principal investigators of penpulimab at Fudan University Shanghai Cancer Center, said: "In China, there remains a significant unmet clinical need for NPC. As the only IgG1 subtype anti-PD-1 monoclonal antibody globally, penpulimab has demonstrated robust efficacy in clinical studies, enhancing the effectiveness of immunotherapy for NPC. The approval for first-line treatment marks a major milestone, as it provides a comprehensive treatment regimen for clinicians and patients, benefiting a large population of NPC patients in China, from first-line to third-line therapy."

Professor Chen Xiaozhong, one of the principal investigators of penpulimab at Zhejiang Cancer Hospital, said: "Nasopharyngeal cancer (NPC) is a highly prevalent malignancy in certain regions, and patients with recurrent or metastatic NPC typically face a poor prognosis. Penpulimab has demonstrated a significantly high response rate and prolonged survival benefits in both first-line treatment of NPC and in patients with metastatic NPC who have failed multiple lines of prior therapy. Additionally, it has shown a favorable safety profile, with a low incidence of immune-related adverse events. "

Dr. Xia Yu, Founder, Chairwoman, CEO, and President of Akeso, said: "We want to extend our sincere gratitude to all the researchers, clinical trial participants, and NPC patients who have contributed to this milestone. With its differentiated design, penpulimab has gained widespread recognition among clinicians and patients for its efficacy and safety in treating diseases like non-small cell lung cancer (NSCLC), Hodgkin lymphoma, and nasopharyngeal cancer. The approval for first-line treatment of advanced NPC will allow more patients in China to benefit from this new PD-1 monoclonal antibody, further improving survival outcomes."

"As key drugs like cadonilimab, ivonescimab, and penpulimab receive approval for a wide range of indications, Akeso’s commitment to innovation and excellence in drug development—from discovery to clinical application—is clearly demonstrated. These advancements are not only improving patient outcomes but also reaffirming our dedication to transforming global healthcare. Moving forward, Akeso will continue to pioneer breakthrough therapies with the potential to set new standards of care, driving positive change in treatment paradigms and improving the lives of patients worldwide."

On March 15, 2025 AbbVie (NYSE: ABBV) reported the final analysis of the confirmatory Phase 3 MIRASOL trial evaluating the efficacy and safety of ELAHERE (mirvetuximab soravtansine-gynx) in women with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer (PROC) compared to chemotherapy (Press release, AbbVie, MAR 15, 2025, View Source [SID1234651160]). At 30.5 months median follow-up, treatment with ELAHERE continued to show significant improvements in progression-free survival (PFS) and overall survival (OS) compared to investigator’s choice (IC) chemotherapy.1 Ovarian cancer patients often present with late-stage disease and are historically first treated with platinum-based chemotherapy, which they may become resistant to and require another therapy, such as ELAHERE.2

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"Ovarian cancer can be devastating, and when cancer cells stop responding to chemotherapy patients may feel hopeless about their journey. The data presented today reinforce the importance of ELAHERE as a transformative therapy for patients with limited options," said Svetlana Kobina, MD, PhD, vice president, oncology medical affairs, AbbVie. "We remain steadfast in our commitment to bring forward innovative therapies that improve the lives of patients with difficult-to-treat cancers."

In the United States, ovarian cancer is the leading cause of death from gynecological cancers.3 Each year, approximately 20,000 women are diagnosed.4 Unfortunately, most patients develop platinum-resistant disease, which is difficult to treat.5 In this setting, single-agent chemotherapies are associated with minimal survival benefit while adding significant toxicity burden.6

The Phase 3 MIRASOL study included 453 patients with high-grade serous epithelial PROC whose tumors express high levels of FRα and had been treated with up to three prior therapies.1 Key findings from the 30.5-month median follow-up include:

ELAHERE treatment achieved superior efficacy versus IC chemotherapy, with a median PFS of 5.59 months versus 3.98 months, representing a 37% reduction in the risk of tumor progression or death (HR 0.63; [95% CI: 0.51, 0.79]) and a higher objective response rate of 41.9% versus 15.9%.
Superior and clinically meaningful overall survival for patients receiving ELAHERE (median 16.85 months) compared to IC chemotherapy (median 13.34 months), representing a 32% reduction in the risk of death (HR 0.68 [95% CI: 0.54, 0.84]).
Other endpoints included safety and duration of response (DOR), which were consistent with the primary data analysis at 13.1-months median follow-up.
The most common treatment-emergent adverse events (TEAEs) occurring in at least 20% of patients in the ELAHERE arm were blurred vision, keratopathy, abdominal pain, fatigue, diarrhea, dry eye, constipation, nausea and peripheral neuropathy. Compared with IC chemotherapy, treatment with ELAHERE was overall associated with lower rates of grade ≥3 TEAEs, serious AEs and discontinuations due to AEs.

"The final data showcase the significant improvement in overall survival benefit of treatment with ELAHERE compared to standard of care chemotherapy," said investigator and presenter, Toon Van Gorp, MD, PhD, Professor of Gynecologic Oncology, University of Leuven. "The significant improvements in survival, along with the well-characterized safety profile, reinforce ELAHERE as an emerging standard of care for difficult-to-treat ovarian cancer and warrants further study of this medicine in earlier treatment settings."

A separate analysis from the Phase 3 MIRASOL study evaluating the impact of [ELAHERE] treatment-emergent ocular events on patient-reported health-related quality of life (HRQoL), will be shared during an oral presentation March 17 at the SGO Annual Meeting scientific plenary session.

ELAHERE was granted full approval by the U.S. Food and Drug Administration in March 2024 and was approved by the European Commission in November 2024. Marketing Authorization Applications for ELAHERE are also under review in multiple other countries.

About the Phase 3 MIRASOL Trial
MIRASOL is a randomized Phase 3 trial of ELAHERE versus investigator’s choice (IC) of single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan). Eligibility criteria include patients with PROC whose tumors express high levels of FRα, using the Ventana FOLR1 RxDx Assay, and who have been treated with up to three prior regimens. The primary endpoint of this trial is progression-free survival (PFS) by investigator assessment. Key secondary endpoints include objective response rate (ORR) and overall survival (OS). The trial enrolled 453 patients. Patients were stratified by number of prior lines of therapy (14% had one prior line of therapy, 39% had two prior lines of therapy, and 47% had three prior lines of therapy) and by IC chemotherapy, with paclitaxel as the most commonly chosen (41%), followed by PLD (36%) and topotecan (23%). Sixty-two percent of patients received prior bevacizumab; 55% received a prior PARP inhibitor.

More information can be found on www.clinicaltrials.gov (NCT04209855).

About ELAHERE
ELAHERE (mirvetuximab soravtansine-gynx) is a first-in-class antibody-drug conjugate (ADC) comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells. Patients requiring access support may call 1-833-ELAHERE or visit www.elahere.com.

ELAHERE U.S. USE and IMPORTANT SAFETY INFORMATION7
What is ELAHERE?
ELAHERE is a prescription medicine used to treat adults with folate receptor-alpha positive ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who:

have not responded to or are no longer responding to treatment with platinum-based chemotherapy and
have received 1 to 3 prior types of chemotherapy.
Your healthcare provider will perform a test to make sure that ELAHERE is right for you.
It is not known if ELAHERE is safe and effective in children.

IMPORTANT SAFETY INFORMATION
What is the most important information I should know about ELAHERE?
ELAHERE can cause serious side effects, including:
Eye problems. Eye problems are common with ELAHERE and can also be severe. Tell your healthcare provider right away if you develop any eye problems during treatment with ELAHERE, including blurred vision, dry eyes, sensitivity to light, eye pain, eye redness, or new or worsening vision changes.

Your healthcare provider will send you to see an eye care professional to check your eyes before you start treatment with ELAHERE, during treatment with ELAHERE, and as needed for any worsening signs and symptoms of eye problems.
Your healthcare provider will prescribe steroid eye drops and lubricating eye drops before you start and during your treatment with ELAHERE. You should use eye drops as directed by your healthcare provider.
Do not wear contact lenses throughout your treatment with ELAHERE unless you are told to use them by your healthcare provider.
What should I tell my healthcare provider before receiving ELAHERE?
Tell your healthcare provider about all of your medical conditions, including if you:

have vision or eye problems.
have numbness or tingling in your hands or feet.
have liver problems.
are pregnant or plan to become pregnant. ELAHERE can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with ELAHERE.
Patients who are able to become pregnant:

Your healthcare provider should do a pregnancy test before you start treatment with ELAHERE.
You should use an effective birth control (contraception) during treatment and for 7 months after your last dose of ELAHERE.
are breastfeeding or plan to breastfeed. It is not known if ELAHERE passes into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of ELAHERE.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking certain other medicines during treatment with ELAHERE may cause side effects.

What are the possible side effects of ELAHERE?
ELAHERE can cause serious side effects, including:

Eye problems. Eye problems are common with ELAHERE and can also be severe. Tell your healthcare provider right away if you develop any eye problems during treatment with ELAHERE, including blurred vision, dry eyes, sensitivity to light, eye pain, eye redness, or new or worsening vision changes.
Lung problems (pneumonitis). ELAHERE can cause severe or life-threatening inflammation of the lungs that may lead to death. Tell your healthcare provider right away if you get new or worsening symptoms, including trouble breathing, shortness of breath, cough, or chest pain.
Peripheral neuropathy. Nerve problems called peripheral neuropathy are common during treatment with ELAHERE and can also be severe. Your healthcare provider will monitor you for signs and symptoms of nerve problems. Tell your healthcare provider if you get new or worsening numbness, tingling, burning sensation or pain in your hands or feet or muscle weakness.
The most common side effects and abnormal labs of ELAHERE include:

• increased liver enzymes in the blood

• feeling tired

• blurred vision

• nausea

• diarrhea

• stomach-area (abdominal) pain

• changes in the cornea (part of the eye)

• peripheral neuropathy

• muscle, bone, or joint pain

• decreased red or white blood cell counts

• decreased platelets

• decreased magnesium level in the blood

• dry eye

• constipation

• vomiting

• decreased albumin level in the blood

• decreased appetite

Your healthcare provider may change your dose of ELAHERE, delay treatment, or completely stop treatment if you have certain side effects.

These are not all of the possible side effects of ELAHERE. Call your doctor for medical advice about side effects. You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‑800‑FDA‑1088.

On March 15, 2025 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), an oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported expanded data in a late-breaking oral presentation from the dose-optimization portion of the REFRαME-O1 trial with luveltamab tazevibulin (luvelta) in patients with platinum resistant ovarian cancer (PROC) at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer (Press release, Sutro Biopharma, MAR 15, 2025, View Source [SID1234651158]). The SGO Annual Meeting will take place from March 14-17, 2025 in Seattle, Washington.

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In this study, luvelta demonstrated encouraging antitumor activity in patients with late-stage ovarian cancer across all levels of Folate Receptor-α (FRα) expression of 25% or greater, including an improved overall response rate (ORR), a low discontinuation rate, and a consistent safety profile across dose levels. Based on these findings, Sutro selected the optimized dose of luvelta: 5.2 mg/kg + G-CSF for two cycles then continued on 4.3 mg/kg.

"These data demonstrate the potential for improved patient responses compared to standard chemotherapy in PROC, especially patients whose FRα expression falls within the range of at least 25% to less than 75% 2+, which remains an important unmet medical need," commented Dr. Jung Yun Lee, Professor, Gynecologic Oncologist, Yonsei Cancer Center and Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Late-Breaking Oral Presentation Highlights:

At the selected optimized dose (5.2 mg/kg), luvelta achieved an ORR of 32%1 and a disease control rate (DCR) of 96% compared to an ORR of 13.8% and a DCR of 69% for the 4.3 mg/kg group.
The demonstrated clinical activity in the 5.2 mg/kg group was consistent in patients across all levels of FRα expression of 25% or greater, with an ORR of 30.8% and a DCR of 100% for positive staining (PS) 2+ ≥75% (eligible for approved FRα-targeting ADC) and an ORR of 33.3%1 and DCR of 91.7%1 for PS2+ < 75%.
Safety was consistent across dosing groups, with no new safety signals observed and neutropenia well-managed.
The majority of patients across both dose cohorts received prior bevacizumab.
The presentation will be accessible through the News & Events page of the Investor Relations section of the company’s website at www.sutrobio.com.

The Company recently announced that it is deprioritizing investment into the development of luvelta across all indications. Sutro continues to explore out-licensing opportunities to deliver the promise of luvelta’s benefit to patients with unmet need in platinum resistant ovarian cancer and beyond.

Immediately after data extraction, one additional patient experienced a confirmed PR and is included in the analysis.

About Luveltamab Tazevibulin

Luveltamab tazevibulin, abbreviated as "luvelta" and formerly known as STRO-002, is a FRα-targeting antibody-drug conjugate (ADC) designed to treat a broad range of patients with ovarian cancer, including those with lower FRα-expression who are not eligible for approved treatment options targeting FRα. Developed and manufactured with Sutro’s cell-free XpressCF platform, luvelta is a homogeneous ADC with four hemiasterlin cytotoxins per antibody, precisely positioned to efficiently deliver to the tumor while ensuring systemic stability after dosing. The U.S. Food and Drug Administration (FDA) has granted luvelta a Fast Track designation for Ovarian Cancer, as well as Orphan and Rare Pediatric Disease designations for CBF/GLIS2 Pediatric AML.