On April 25, 2025 Onc.AI, a digital health company developing advanced AI-driven clinical management solutions for oncology, reported that findings from a recent collaboration with global biopharma company GSK using Onc.AI’s FDA breakthrough-designated Serial CTRS AI model will be presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Onc AI, APR 25, 2025, View Source [SID1234652184]). The study externally evaluated Serial CTRS in GSK’s GARNET Phase I clinical trial (NCT02715284) Cohort E, that enrolled patients with advanced non-small cell lung cancer (NSCLC) treated with dostarlimab, GSK’s anti-PD-1 checkpoint inhibitor.

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Results, highlighted in a poster presentation during the Predictive Biomarkers 2 session (poster #21, April 27, 2025, 2-5pm), demonstrated that the Serial CTRS biomarker, leveraging routine CT imaging without manual annotations, improved prediction of overall survival (OS) compared to traditional surrogates including RECIST 1.1 response criteria and tumor volume. The analysis was conducted through an independent and blinded retrospective validation study carried out by GSK. In particular, Serial CTRS showed the ability to distinguish patients with intermediate versus high probabilities of 12-month OS (HR: 2.91, 95% CI: 1.16–7.31), outperforming RECIST 1.1 (HR: 1.34, 95% CI: 0.57–3.13) and tumor volume change assessments (HR: 1.00, 95% CI: 0.43–2.34). This enhanced predictive performance supports Onc.AI’s commitment to establishing Serial CTRS as a new standard for automated, AI-based imaging endpoints in the early assessment of treatment response, seamlessly integrating into standard imaging workflows across diverse therapeutic regimens.

Key findings include:

Serial CTRS improved discrimination between intermediate and high probabilities of overall survival compared to RECIST 1.1 and tumor volume changes.
Serial CTRS remained a significant predictor of overall survival after adjusting for known prognostic factors, such as age, baseline tumor volume, and PD-L1 Tumor Proportion Score (TPS).
"This important milestone for Serial CTRS builds on a recent breakthrough-designation from FDA," said Akshay Nanduri, CEO of Onc.AI. "The success of this validation study and ongoing continued collaboration with GSK reflects the strength and robustness of model performance. This can only be achieved using advanced Deep Learning combined with methods for harmonizing diverse imaging data and the breadth of our training data. Onc.AI’s high-quality data on thousands of patients has been sourced from dozens of healthcare systems representing hundreds of clinics across the United States and other international cancer centers, ensuring unparalleled diversity in training, test and validation."

"As the past head of multiple Phase I clinics at top cancer centers, I believe that Onc.AI’s innovation with Serial CTRS could transform the pharma clinical development process from Phase I to Phase III studies," said George R. Simon, MD, FACP, FCCP, Vice President of Oncology at OhioHealth.

On April 25, 2025 Iksuda Therapeutics (Iksuda), the developer of class leading, clinically validated antibody drug conjugates (ADCs) reported that it will present three posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois (25-30 April) (Press release, Iksuda Therapeutics, APR 25, 2025, View Source [SID1234652182]). The posters cover the Company’s new payload class, the ProAlk series, its CA242-directed ADC, IKS04, being developed for the treatment of gastrointestinal (GI) cancers, and its proprietary PermaLink conjugation chemistry.

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Iksuda will introduce its new ProAlk payload class which has a novel protein alkylating mechanism and is incorporated in ADCs in a prodrug format for enhanced targeting precision. ProAlk is active across a broad range of tumours and has been designed for optimal ADC relevance. It is associated with potent bystander activity and is MDR-resistant. Its novel mechanism will help to address the growing and significant challenge of ADC sequencing, where differentiation from tubulin and topoisomerase I inhibitor payloads will become imperative. Iksuda is building a pipeline of ProAlk driven ADCs which incorporate its proprietary PermaLink conjugation chemistry for ADC stability and tumour-selective payload activation and release for enhanced precision and safety.

The Company will also present a poster on IKS04, its CA242-directed ADC for the treatment of GI cancers and which is in IND-enabling studies. IKS04 uses a pro-drug approach for the tumour-specific delivery of a highly potent pyrrolobenzodiazepine (PBD) payload, avoiding the typical toxicity profile seen in traditional PBD ADCs. In preclinical trials, IKS04 is associated with in vivo efficacy which is substantially improved over benchmark ADCs in all tumour models, and a superior therapeutic index over all other PBD-based solid tumour ADC programs. IKS04 will be administered via pre-administration of naked antibody – a novel dosing regimen in the ADC field – to overcome high expression abundance and enable higher tumour penetration and consistent levels of efficacy across tumours. IKS04 is expected to enter clinical development in GI cancers by the end of 2025.

In addition, Iksuda will highlight its proprietary PermaLink conjugation chemistry, which is used across its early-stage ADC platform alongside the Company’s glucuronide linker formats and novel ProAlk payload. PermaLink offers a simple, scalable and highly stable bioconjugation method as an alternative to maleimide-based conjugation, enabling highly stable ADCs with favourable anti-tumour activity and safety.

Dr Dave Simpson, Chief Executive Officer, Iksuda Therapeutics, said:

"These three poster presentations at AACR (Free AACR Whitepaper) demonstrate Iksuda’s leadership in ADC innovation as we unveil our novel ProAlk payload class, overcoming the challenges in ADC sequencing and which will drive Iksuda’s deepening pipeline. With two clinical-stage programs, a growing pipeline of class leading ADCs and our expanding, innovative platforms, we are strongly positioned to progress new and promising ADCs to deliver improved outcomes for patients living with cancer. We look forward to progressing IKS04 into clinical development for GI cancers later this year, an area of high unmet need with limited effective treatment options and poor five-year survival rates for the significant number of patients with advanced disease."

Poster Presentation details:

ProAlk

Abstract Title:

PA289, a prodrug linker-payload with a novel mechanism of action for the development of antibody drug conjugates

Session Title:

Antibody-Based Cancer Therapeutics 1

Date/Time:

April 28, 2025 9:00 AM – 12:00 PM

Location:

Poster Section 15

Poster Number:

1579/28

IKS04

Abstract Title:

IKS04, an antibody drug conjugate with a highly potent DNA crosslinker payload for the treatment of gastrointestinal cancers

Session Title:

Antibody-Based Cancer Therapeutics 2

Date/Time:

April 28, 2025 2:00 PM – 5:00 PM

Location:

Poster Section 15

Poster Number:

2885/24

PermaLink

Abstract Title:

PermaLink, a stable and scalable bioconjugation platform as an alternative to maleimide-based conjugation

Session Title:

Antibody-Based Cancer Therapeutics 1

Date/Time:

April 28, 2025 9:00 AM – 12:00 PM

Location:

Poster Section 15

Poster Number:

1570/19

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]).

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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]).

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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.

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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).