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.

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!

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 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, reported new preclinical data for MaaT034, the Company’s next generation product, showing compelling anti-tumor efficacy results in germ-free mice at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago, Illinois, taking place from April 25 to 30, 2025 (Press release, MaaT Pharma, APR 28, 2025, View Source [SID1234652236]).

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!

MaaT Pharma has built a versatile platform combining two complementary approaches. The first one leverages a GMP-compliant approach to produce standardized donor-derived therapies (MaaT013, MaaT033) using pooled donations, proven to restore a rich and diverse gut microbiome for patients with severe dysbiosis and currently in late-stage of clinical evaluation (Phases 2 and 3). In parallel, the Company is advancing a next-generation, AI-driven co-culture technology to develop a donor-independent synthetic microbiome ecosystem at large industrial scale targeting indication-specific diseases. MaaT034, the first-in-class co-cultured product, aims to optimize intestinal microbiome functions and to improve patient responses to immunotherapy in combination with Immune Checkpoint Inhibitors.

Below are the key results presented at AACR (Free AACR Whitepaper) for MaaT034:

Metagenomic analysis shows that MaaT034 reproduces the microbial functions of MaaT013 – the Company’s lead asset, currently evaluated in the randomized Phase 2 PICASSO trial in combination with immune checkpoint inhibitors (ICI), ipilimumab (Yervoy) and nivolumab (Opdivo) for unresectable or metastatic melanoma.
MaaT034 improves DC-mediated T cell activation and potentiates anti-tumor effects mediated by anti-PD-1 checkpoint blockade in vitro.
70% of MaaT034 microbial species engraft in mice, ensuring an enduring presence of beneficial bacteria in the gut environment.
MaaT034 increases the production of key microbial-derived metabolites such as short-chain fatty acids in germ-free mice. This translates into an improved gastrointestinal physiology as evidenced by gut mucosal restoration.
MaaT034 optimizes anti-PD1 mediated activity in tumor-bearing, germ-free mice. While anti-PD1 alone reduced tumor growth by 10%, the combination of anti-PD1 and MaaT034 resulted in a 83.7% tumor growth reduction (compared to a 24.2% reduction when using a single strain of Akkermansia muciniphila bacteria). These results demonstrate that improved tumor control is achieved with anti-PD1 in combination with MaaT034, as compared to PD-1 alone or in combination with a reference single bacterial strain.
"These positive data in tumor-bearing mice demonstrate the significant potential of MaaT034 as a microbiome ecosystem therapy candidate and provide a robust basis for the progression of this therapy into clinical development for solid tumors. We look forward to further evaluating the potential benefits of MaaT034 in the next phases of our research," said Gianfranco Pittari, MD PhD, Chief Medical Officer, MaaT Pharma.

Upcoming conferences participation

May 5-6, 2025 – Swiss Biotech Day, Basel
May 13, 2025 – Forum Midcaps Gilbert Dupont, Paris
June 12-15 – European Hematology Association (EHA) (Free EHA Whitepaper) Congress, Milan, IT
June 16-19, 2025 – Bio International Convention, Boston, MA – Company Presentation
June 18-19, 2025 – Portzamparc Conference Mid & Small Caps 2025, Paris
September 25, 2025 – KBC Healthcare Conference, Brussels
About MaaT034

MaaT034, currently in preclinical development, is a next-generation donor-independent full ecosystem synthetic microbiome therapy, dedicated to improving patient responses to immunotherapy in combination with Immune Checkpoint Inhibitors. Developed using the Company’s co-culturing proprietary MET-C platform, MaaT034 is optimized for large-scale production in oncology. Previous presented preclinical data showed that MaaT034 produced key metabolites, recognized as promoting gut barrier restoration and modulating immune responses, such as Short-Chain Fatty Acids (SCFA), secondary bile acids, and tryptophan derivatives. These data support the role of MaaT034 in gut barrier repair and in T cell reactivation either in combination with anti-PD1 or with anti-PD-L1. By enhancing gut barrier repair and modulating immune responses, MaaT034 is expected to complement the action of these immunotherapeutic agents, potentially improving their efficacy in treating solid tumors cancer.

On April 28, 2025 Boehringer Ingelheim reported new and updated data from the Beamion LUNG-1 trial evaluating zongertinib in previously treated patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer (NSCLC) (Press release, Boehringer Ingelheim, APR 28, 2025, View Source [SID1234652268]). The data was featured in the official press program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine.

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!

"These data presented at AACR (Free AACR Whitepaper) 2025 suggest that zongertinib may offer a new approach to treating patients with non-small cell lung cancer with activating HER2 mutations," said the trial’s coordinating investigator, Dr. John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. "Notably, more than 70% of patients experienced a tumor response, which is highly meaningful for those with this subtype of lung cancer. If approved by the FDA, zongertinib would be the first oral, targeted treatment option that addresses an unmet need for these patients."

Data from the most recent analysis showed durable response and clinically meaningful results with zongertinib in previously treated patients with advanced NSCLC who have HER2 mutations within the tyrosine kinase domain (TKD) (N=75). The ORR was 71% (95% CI: 60-80), with 7% complete response, 64% partial response, and 96% disease control in previously treated patients. Additionally, zongertinib had intracranial activity in previously treated patients (n=27, who were evaluable) with brain metastases, with 41% achieving response and 81% disease control. At AACR (Free AACR Whitepaper) 2025, the median DoR of 14.1 and median PFS of 12.4 months were presented for the first time.

Itziar Canamasas, Global Head of Oncology at Boehringer Ingelheim, said: "Zongertinib has the potential to reset the benchmark for patients with HER2-mutant advanced non-small cell lung cancer, a patient population that has historically faced a poor prognosis. At Boehringer, we take cancer care personally; these updated data reaffirm our approach of addressing areas with high unmet need and letting our research guide us to where we can have the biggest impact for patients."

Additional analyses of previously treated patients with HER2 mutations demonstrated zongertinib’s clinically meaningful results

Initial results in patients with advanced NSCLC with HER2 mutations in the TKD, who were previously treated with both platinum-based chemotherapy and subsequent HER2-directed antibody drug conjugates (ADC) (N=31), demonstrated an ORR of 48% (95% CI: 32-65) with 97% (95% CI: 15-52) of patients achieving disease control. An exploratory cohort (n=20) that included previously treated patients with advanced NSCLC with HER2 mutations outside of the TKD demonstrated an investigator-assessed ORR of 30% (95% CI: 15-52) and a DCR of 65% (95% CI: 43-82). This is the largest known dataset of patients with previously treated advanced NSCLC who have HER2 mutations outside the TKD. Both of these data sets were presented at AACR (Free AACR Whitepaper) 2025 and are included in The New England Journal of Medicine publication.

The data presented at AACR (Free AACR Whitepaper) 2025 demonstrated a manageable safety profile for zongertinib with no drug-related deaths, cases of interstitial lung disease (ILD) or cardiotoxicity reported. The most commonly reported adverse event (AE) was grade 1 diarrhea, with low incidence of grade ≥3 drug-related events (17%) in patients with TKD mutations (N=75).

AACR 2025 presentation: summary of key efficacy endpoints

Endpoint

Patients with TKD mutations (N = 75)

Patients with TKD mutations and
prior HER2-directed ADC treatment (N = 31)

Patients with non-TKD mutations (n = 20)

ORR, %

95% CI

71*

60-80

48*

32–65

30**

15-52

CR, %

7*

3*

0**

PR, %

64*

45*

30**

DCR, %

95% CI

96*

89-99

97*

84-99

65**

43-82

Median DoR

95% CI

14.1 months***

6.9–NE

n/a

n/a

Median PFS

95% CI

12.4 months***

8.2–NE

n/a

n/a

*Confirmed response by BICR according to RECIST v1.1
**Confirmed response by investigator review according to RECIST v1.1
*** Median DoR and median PFS are based on Kaplan Meier estimates

About non-small cell lung cancer (NSCLC)
Lung cancer claims more lives than any other cancer type1 and the incidence is set to increase to over 3 million cases worldwide by 2040.2 NSCLC is the most common type of lung cancer.3 The condition is often diagnosed at a late stage,4 and fewer than 3 in 10 patients are alive five years after diagnosis.5 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 mutations (or gene alterations).6 Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.7

About zongertinib
Zongertinib is an investigational irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing wild-type EGFR, thereby limiting associated toxicities. This orally administered, targeted therapy was granted FDA Fast Track Designation in 2023, followed by Breakthrough Therapy Designation in the U.S. and China for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have received prior systemic therapy. An application for accelerated approval was granted Priority Review status by the FDA in February 2025. In addition, Japan’s Pharmaceuticals and Medical Devices Agency granted Orphan Drug Designation to zongertinib.

A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy. In addition, zongertinib is being evaluated in Beamion LUNG-2 (NCT06151574)4, a global Phase III trial, compared to standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic NSCLC who have activating HER2 TKD mutations.

About the Beamion clinical trial program
Beamion LUNG-1 (NCT04886804): An open-label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with advanced non-small cell lung cancer with a specific mutation in the HER2 gene. Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD mutations to evaluate zongertinib compared with standard of care.

On April 28, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical stage biopharmaceutical company, reported it will be presenting at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting to be held May 30-June 3, 2025 at McCormick Place, Chicago, Ill (Press release, Kairos Pharma, APR 28, 2025, View Source [SID1234652284]).

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 poster is titled, "Effect of KROS 101, a small molecule GITR ligand agonist, on T effector cells, T reg cells and intratumoral CD8 T cell cytotoxicity," and will be presented on June 2.

John Yu, M.D., Kairos CEO commented, "We look forward to the opportunity to continue to share data regarding our platform assets at one of the most prestigious oncology meetings in the world. We believe that KROS 101 has the potential to help optimize cancer treatment and we look forward to discussing our findings with the medical and scientific communities."

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]).

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!

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.