On April 25, 2025 NextPoint Therapeutics, a clinical-stage biotechnology company launching a new world of precision therapeutics through its leading scientific work on the novel B7-H7 axis, reported it will present compelling data on NPX125, its lead B7-H7-targeting antibody-drug conjugate (ADC) with a proprietary novel linker technology, at the American Association for Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago (Press release, NextPoint Therapeutics, APR 25, 2025, View Source [SID1234652181]).

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!

NPX125, which utilizes NextPoint’s proprietary linker technology paired with a clinically validated topoisomerase 1 inhibitor payload in a DAR8 (drug-antibody ratio) format, is initiating IND-enabling work with an anticipated IND filing in mid-2026. Leveraging B7-H7’s superb internalization profile that enables efficient payload delivery, the company expects this first-in-class ADC targeting B7-H7 to enter the clinic shortly thereafter, expanding NextPoint’s multimodal approach to targeting the B7-H7 axis.

Poster Details
Title: B7-H7 is a novel ADC target for solid tumors and shows potent activity with multiple payload-linker technologies
Abstract Number: 7336
Section: 40
Session Date/Time: Wednesday, April 30, 2025, 9:00 AM – 12:00 PM

"The data we’re presenting at AACR (Free AACR Whitepaper) validate the B7 family as an outstanding ADC target with a highly favorable profile compared to other clinically successful targets and even members of the B7 family, like B7-H3 and B7-H4," said Tatiana Novobrantseva, PhD, Chief Scientific Officer at NextPoint Therapeutics. "NPX125 emerged as the lead candidate among multiple B7-H7-targeting ADCs tested, and has demonstrated remarkable internalization kinetics, potent cytotoxicity and strong anti-tumor activity across tumor models with varying levels of B7-H7 expression, supporting our conviction in its potential to deliver meaningful benefits to patients."

Key Program Attributes include:

Superior ADC Properties
NPX125 via its interaction with B7-H7 demonstrated efficient internalization across many different tumor cell lines
Showed both direct and bystander cytotoxic activity, critical for addressing tumor heterogeneity
NPX125 demonstrated superior serum stability in rat pharmacokinetic studies
Robust developability profile due to antibody selection and unique linker properties
Strong Anti-Tumor In Vivo Efficacy
NPX125 achieved tumor regressions in multiple preclinical mouse models with variable B7-H7 expression levels
Additional Poster Presentations at AACR (Free AACR Whitepaper)
NextPoint will also present three additional posters at AACR (Free AACR Whitepaper) showcasing its comprehensive approach to targeting the B7-H7 axis:

"B7-H7-CD3 bispecific T cell engaging antibodies demonstrate potent anti-tumor activity in B7-H7+ preclinical tumor models" (Abstract #1556)
"Comprehensive analysis of B7-H7/HHLA2 expression in pan-solid tumors and its potential significance in anti-tumor immunity" (Abstract #3302)
"Safety and tolerability of NPX372, a novel B7-H7 bispecific T cell engaging antibody" (Abstract #4354)
The poster presentations are available in the "News & Publications" section of NextPoint’s website: View Source

About B7-H7
B7-H7 (also known as HHLA2) represents an ideal tumor-targeting antigen, with limited normal tissue expression and upregulation on a broad range of solid tumor histologies. Unlike other B7 family members which may be expressed on tumor cells and immune cell populations, B7-H7 expression is detectable only on tumor epithelial cells, which makes it a more specific tumor-targeting antigen. B7-H7’s expression across multiple tumor types, coupled with its role in immunomodulation in the tumor microenvironment, positions it as a promising target for precision therapeutic approaches.

On April 25, 2025 Parabilis Medicines (formerly Fog Pharmaceuticals), a clinical-stage biopharmaceutical company committed to creating extraordinary medicines for people living with cancer, reported preclinical data demonstrating first-in-industry targeted degradation of ERG at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which begins today in Chicago, Illinois (Press release, Parabilis Medicines, APR 25, 2025, View Source [SID1234652180]).

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!

ERG has been a long-recognized high-value target in prostate cancer, where ERG fusions have been implicated in 40-50% of all cases. In metastatic castrate-resistant prostate cancer (mCRPC) specifically, the TMPRSS2-ERG gene fusion is associated with more aggressive disease and may predict resistance to certain therapies, such as PARP inhibitors. However, ERG has been undruggable by conventional inhibitors or first-generation degraders because it lacks small molecule binding pockets.

Potent and specific degradation of ERG has been achieved with Helicon peptide degraders both in vitro and in vivo, leading to substantial tumor growth inhibition in multiple mouse models of prostate cancer. The data represent the first pharmacological proof-of-concept for ERG dependency in preclinical models of ERG-fusion prostate cancer.

"Parabilis’s Helicon peptide degraders have thrilling potential to expand the reach of targeted protein degradation to traditionally ‘undruggable’ targets," said Mathai Mammen, M.D., Ph.D., Chairman and CEO of Parabilis Medicines. "These first compelling data from our ERG program validate our novel approach to degradation. The data also support the continued progress of our ERG degrader toward clinical trials, where it has the potential to be a meaningful therapeutic for patients with metastatic prostate cancer."

Highlights of the data presented at AACR (Free AACR Whitepaper) include:

In mice implanted with prostate cancer cell-derived xenograft (CDX) tumors, administration of the ERG degrader produced >90% tumor ERG degradation through 7 days post dose. This corresponded to suppression of ERG’s downstream effects on target gene ARHGDIB.
In both patient- and cell-line derived xenograft (PDX and CDX) models of TMPRSS2-ERG fusion prostate cancer, Parabilis’s ERG degrader significantly inhibited tumor growth.
RNA sequencing expression analyses indicated that Parabilis’s ERG degrader downregulated Myc target genes.
Parabilis’s ERG degrader uses Helicon technology to bind directly to the ERG protein and, through its attached E3 ligand, directs the ERG protein to the ubiquitin-proteasome pathway for degradation. The company anticipates entering IND-enabling toxicology studies in 2025.

Parabilis’s prostate cancer franchise additionally includes a selective degrader of active androgen receptor (AR), which binds at a different site from approved drugs, and circumvents known resistance mechanisms that arise in response to AR antagonist therapies. Together, Parabilis’s degraders of ERG and AR could potentially provide novel therapeutic approaches for patients with mCRPC.

On April 25, 2025 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported the publication of 3 abstracts for poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Obsidian Therapeutics, APR 25, 2025, View Source [SID1234652179]). In addition to a trial-in-progress study design update on the ongoing multicenter study Agni-01 (NCT06060613), Obsidian will share preclinical data from our cytoDRiVE platform demonstrating spatiotemporal regulation of membrane-bound IL12 in syngeneic solid tumor models and preclinical data on OBX-115 TIL phenotype starting from NSCLC tumor tissue.

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!

Obsidian is presenting new preclinical data from its cytoDRiVE regulation platform, further demonstrating the ability to unlock the therapeutic window of potent cytokines and broaden the reach of armored cell therapies. The poster for abstract LB025 demonstrates the application of Obsidian’s regulatable cytoDRiVE platform to enhance antigen-responsive ("spatial") promoter-induced activation by adding a critical pharmacologically regulatable ("temporal") signal to exert tight "spatiotemporal" control over IL12 expression1, resulting in a positive impact on safety and tumor control in syngeneic solid tumor models.

Obsidian will also present preclinical data from a multimodal phenotyping analysis comparing OBX-115 TIL generated with its proprietary manufacturing process to conventional, non-engineered TIL using NSCLC tumor samples. The poster for abstract LB359 provides evidence that, as observed with melanoma2, the OBX-115 process generates a minimally exhausted, CD8+ enriched and memory "stem-like" T-cell phenotype. Additionally, the tumor reactive gene signature analysis showed that the drug product is enriched for putative tumor-reactive T-cell clonotypes.

Obsidian Posters at AACR (Free AACR Whitepaper) 2025:

Spatiotemporally regulated expression of membrane-bound interleukin 12 (mbIL12) for armored adoptive cell therapy (ACT) shows strong antitumor activity in syngeneic solid tumor models without overt toxicity (Abstract LB025)
Presenting Author: Ross T, Obsidian Therapeutics
Poster: Sunday, April 27, 2:00-5:00pm CT
OBX -115 TIL from non-small cell lung cancer (NSCLC) are enriched for putative tumor-reactive, stem-like T cells with enhanced tumor cytotoxicity: Results from multimodal phenotyping analysis (Abstract LB359)
Presenting Authors: Schoenfeld AJ, Memorial Sloan Kettering Cancer Center
Poster: Tuesday, April 29, 2:00-5:00pm CT
Trial in progress: Phase 1/2 study of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced solid tumors (Abstract CT244)
Presenting Author: Shoushtari AN, Memorial Sloan Kettering Cancer Center
Poster: Tuesday, April 29, 2:00-5:00pm CT
1 Smith et al., SITC (Free SITC Whitepaper) 2024 (Abstract 463).
2 Bernatchez et al., ISCT 2024 (Abstract 909).

About OBX-115

Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. Obsidian is investigating OBX-115 in the phase 1/2 Agni-01 multicenter trial in patients with advanced solid tumors (NCT06060613).

On April 25, 2025 InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company, reported that its BTK inhibitor orelabrutinib received approval from the China National Medical Products Administration (NMPA) for the first-line treatment of patients with chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) (Press release, InnoCare Pharma, APR 25, 2025, View Source [SID1234652178]). The approval of the first-line CLL/SLL treatment will enable orelabrutinib to benefit an even broader population of lymphoma patients.

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!

Orelabrutinib has been approved for the treatment of three indications in China, including relapsed and refractory (R/R) CLL/SLL, r/r mantle cell lymphoma (R/R MCL) and r/r marginal zone lymphoma (R/R MZL), all of which have been covered in the National Reimbursement Drug List.

Jianyong Li, the principal investigator of the clinical trial and a professor at the Jiangsu Province Hospital, said: "Orelabrutinib has demonstrated excellent efficacy and safety in the treatment of B-cell malignancies such as R/R CLL/SLL since its launch in 2020, showing a higher complete response rate. The first-line approval means more lymphoma patients will benefit from this highly effective treatment regimen. The study showed a complete response rate as high as 12.1%, which will bring new hope to the treatment of hematological tumors in China."

Lugui Qiu, the principal investigator of the clinical trial and a professor at the Blood Diseases Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, said, "Despite the challenges posed by the COVID-19 pandemic in initiating the study, enrolling patients and patient management, orelabrutinib demonstrated significant efficacy and good safety in first-line treatment of CLL/SLL. It also provides an effective treatment option for high-risk patients and those with comorbidities, both in clinical research and real-world settings."

Jun Ma, professor at the Harbin Blood Disease and Oncology Research Institute, said, "With the approval of orelabrutinib for first-line CLL/SLL treatment and the accumulation of additional real-world data, more lymphoma patients will benefit. Furthermore, orelabrutinib has been listed as a Class I recommendation for first-line treatment of CLL/SLL in the CSCO lymphoma guidelines. We look forward to more extensive and longer follow-up data on orelabrutinib to guide clinical practice and offer better treatment options for more lymphoma patients."

Jun Zhu, professor at Beijing Cancer Hospital said, "The prospect of orelabrutinib in the treatment of hematological tumors is remarkable. Its high selectivity and low off-target effects give it advantages in both efficacy and safety. We believe that with the extensive use of orelabrutinib in first-line treatment, more patients will benefit from this novel therapy."

Dr. Jasmine Cui, Co-founder, Chairwoman and CEO of InnoCare, said: "We are delighted to see the approval of orelabrutinib for the first-line treatment of CLL/SLL. This marks another important milestone for our company in hematological malignancies. We sincerely thank all the physicians, patients and employees who have worked tirelessly on this study. We look forward to bringing new hope and treatment options to more lymphoma patients."

Orelabrutinib is a novel BTK inhibitor developed by InnoCare. With high target selectivity, it can avoid adverse events related to off-target effects and improve safety and efficacy.

CLL/SLL, one of the most prevalent forms of leukemia, is an indolent malignancy of B lymphocytes. Globally, there are 191,000 newly diagnosed CLL cases each year, with 61,000 related deaths1. The incidence rate of CLL/SLL is on the rise in China.

On April 25, 2025 Incyte (Nasdaq:INCY) reported that the Company will present new early-stage data from its oncology portfolio at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago, IL, from April 25–30 (Press release, Incyte, APR 25, 2025, View Source [SID1234652177]).

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!

"At AACR (Free AACR Whitepaper) we will be presenting data from early-stage programs across our oncology portfolio, including for patients with myeloproliferative neoplasms, ovarian cancer and other solid tumors," said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. "These data will guide our approach as we advance our pipeline and seek to transform the treatment landscape for patients with cancer and myeloproliferative neoplasms."

Abstracts accepted for presentation at AACR (Free AACR Whitepaper) include:

Mini Symposium

INCB177054

INCB177054: A Novel, Potent, Orally Bioavailable DGKα/ζ Dual Inhibitor Enhances T-Cell Function and Demonstrates Potent Antitumor Activity
(Session Title: Novel Antitumor Agents. April 28, 4:50 p.m. – 5:05 p.m. ET (3:50 p.m. – 4:05 p.m. CT). Abstract #3789.))

Poster Presentations

INCA33890

INCA33890 Increases CD8+ T-Cell Effector Function Compared with pembrolizumab as Assessed by Single-Cell RNA Sequencing in Human PD-1xTGFβR2 Knock-In Mouse Model (Session Title: Immune Fitness and Metabolic Regulation of Cancer Immunity​. April 29, 10:00 a.m. – 1:00 p.m. ET (9:00 a.m. – 12:00 p.m. CT). Abstract #4861.))

INCA33890, a Bispecific Antibody Targeting PD-1 and TGFβR2, Shows Enhanced Immune Responses in Models of Ovarian Cancer
(Session Title: Antibodies 3: Multi-Target Checkpoint Inhibitors and Immune Activators. April 29, 3:00 p.m. – 6:00 p.m. ET (2:00 – 5:00 p.m. CT). Abstract #6074.))

PD-1xTGFβR2 Bispecific Biclonics Antibody INCA33890 Augments Human T-Cell Effector Functions In Vitro and Ex Vivo
(Session Title: Antibodies 3: Multi-Target Checkpoint Inhibitors and Immune Activators​. April 29, 3:00 p.m. – 6:00 p.m. ET (2:00 – 5:00 p.m. CT). Abstract #6071.))

INCB057643

INCB057643, a Bromodomain and Extra-Terminal (BET) Protein Inhibitor, Improved Bone Marrow Function and Shifted Megakaryopoiesis to Erythropoiesis in Patients with Myeloproliferative Neoplasms (MPNs)
(Session Title: Molecular Genetics and Epigenetics of Tumors​. April 30, 10:00 a.m. – 1:00 p.m. ET (9:00 a.m. – 12:00 p.m. CT). Abstract #7188.))

Novel Role of INCB057643, a Bromodomain and Extra-Terminal (BET) Protein Inhibitor, in Myeloid Cell Regulation and Immunosuppressive Tumor Environment Remodeling in Myelofibrosis (MF)
(Session Title: Molecular Genetics and Epigenetics of Tumors​. April 30, 10:00 a.m. – 1:00 p.m. ET (9:00 a.m. – 12:00 p.m. CT). Abstract #7184.))

Association of Cyclin E1 Expression with Genomic Instability in Ovarian Cancer
(Session Title: Origins and Mechanisms of Genomic Instability​. April 28, 3:00 p.m. – 6:00 p.m. ET (2:00 – 5:00 p.m. CT). Abstract #2846.))