On April 25, 2025 DELFI Diagnostics, Inc., developer of innovative blood-based tests that leverage cell-free DNA (cfDNA) fragmentomics for cancer detection and monitoring, reported its team is presenting at the upcoming 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL (Press release, Delfi Diagnostics, APR 25, 2025, View Source [SID1234652163]). DELFI is showcasing its groundbreaking DELFI-TF technology for treatment response monitoring alongside its early detection capabilities.

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"Our presentations at AACR (Free AACR Whitepaper) highlight how DELFI’s fragmentomics platform is transforming both early cancer detection and treatment monitoring," said Victor E. Velculescu, MD, PhD, DELFI Diagnostics Founder and Board Director. "The DELFI technology represents a paradigm shift in how we detect cancer by combining genome-wide fragmentomics of DNA in the blood with AI algorithms for high sensitivity in the screening setting as well as for noninvasively measuring treatment efficacy in advanced cancer patients. "

DELFI is presenting multiple podium and poster sessions at AACR (Free AACR Whitepaper), including:

Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection presented by Victor E. Velculescu, MD, PhD

Tuesday, April 29, 11:06 AM – 11:26 AM CT
Room S100 BC (Grand Ballroom BC) – McCormick Place South
Leveraging the cfDNA fragmentome to predict immunotherapy response presented by Valsamo Anagnostou, MD, PhD

Monday, April 28, 3:05 PM – 3:20 PM CT
Room S105 – McCormick Place South
Analysis of lung cancer clinical characteristics using cell-free DNA fragmentomes presented by Lorenzo Rinaldi, PhD

Monday, April 28, 9:00 AM – 12:00 PM CT
Section 28, Poster 29
Cell-free DNA fragmentomes for treatment response monitoring in patients with metastatic colorectal cancer: the DOLPHIN study presented by Denise E. Van Steijn

Monday, April 28, 2:00 PM – 5:00 PM CT
Section 29, Poster 6
DELFI Diagnostics has clinically validated FirstLook Lung, its blood test designed to improve early detection of lung cancer, which remains the leading cause of cancer deaths in the United States. At the AACR (Free AACR Whitepaper) Annual Meeting, DELFI will present research data on early detection in additional cancer types, including liver, ovarian, and other cancers.

In addition to the company’s early detection efforts, DELFI launched the DELFI-TF* research service in February 2024. DELFI-TF actively guides critical oncology drug development decisions at five top 20 pharmaceutical companies. The technology is designed to deliver critical insights at every stage of the metastatic cancer journey, from baseline assessment and response monitoring to resistance detection and continuous insight across all treatment lines. Requiring just 800µl of plasma, DELFI-TF offers a mutation-independent monitoring solution with a 99% success rate and results typically available in 10-14 business days.

DELFI-TF’s performance has been validated through clinical studies across multiple cancers, including colorectal, lung, pancreatic, breast, melanoma, and head and neck. It has demonstrated its ability to quantify tumor burden without requiring mutation profiling. This strongly correlates with Mutant Allele Frequency (MAF) measurements even when specific mutations are undetectable.

"Lack of efficacy is still the most common reason for Oncology Phase II clinical trials to fail during development, demonstrating the need for improved methods for detection of efficacy of new medical entities in early clinical trials," said Nicholas C. Dracopoli, PhD, Chief Scientific Officer and Co-Founder. "DELFI-TF offers pharmaceutical developers a streamlined, cost-effective solution for monitoring treatment response earlier and more efficiently than traditional methods."

To learn more about DELFI Diagnostics and its innovative fragmentomics platform, visit them at AACR (Free AACR Whitepaper) Booth #2060 or visit www.delfidiagnostics.com.

*The DELFI-TF Assay and related services are for Research Purposes Only and are not intended for diagnostic procedures or applications.

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 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported preclinical data demonstrating the anti-tumor activity of OP-3136, a novel small molecule that potently and selectively inhibits lysine acetyltransferase 6 (KAT6), in prostate, ovarian, and non-small cell lung cancer (NSCLC) models (Press release, Olema Oncology, APR 25, 2025, View Source [SID1234652148]). These findings are being presented in a late-breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 25-30 in Chicago, Illinois.

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"These data showcase the potential of OP-3136 for the treatment of challenging cancers beyond breast cancer," said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. "OP-3136 has shown inhibition across all models explored, and we were excited to observe potent tumor growth inhibition and sustained tumor regression with OP-3136 as a monotherapy in ovarian cancer models. We are actively recruiting the Phase 1 trial of OP-3136 in multiple solid tumor types and will continue to explore its potential in other indications of high unmet need."

Poster Presentation Details
Title: OP-3136, a selective KAT6 inhibitor, demonstrates anti-tumor activity in prostate, ovarian, and non-small cell lung cancer preclinical models
Poster/Abstract: LB166
Session: Late-Breaking Research: Tumor Biology 2
Date/Time: April 28, 2025, from 9:00am-12:00pm CT / 10:00am-1:00pm ET
Presenter: Dr. Gopinath S. Palanisamy, DVM, Ph.D.

Key findings include:

OP-3136 showed potent anti-proliferative activity in multiple ovarian, NSCLC, and prostate cell lines in vitro.
OP-3136 showed activity that was independent of KAT6 amplification or over expression.
OP-3136 monotherapy demonstrated anti-tumor activity in in vivo xenograft models of ovarian (OVCAR3), NSCLC (LCLC-97TM1), and prostate (22Rv1) cancers.
In the OVCAR3 model, OP-3136 monotherapy demonstrated sustained tumor regression across the 28-day study period and robust tumor growth inhibition.
In the LCLC-97TM1 model, OP-3136 monotherapy demonstrated tumor growth inhibition comparable to ribociclib and, when combined with ribociclib, demonstrated synergy and enhanced anti-tumor activity.
In the 22Rv1 model, OP-3136 inhibited tumor growth in a dose-dependent manner and, when combined with docetaxel, resulted in enhanced anti-tumor activity.
These data indicate OP-3136 may be effective in treating ovarian, lung, and prostate cancer indications in addition to breast cancer.
A copy of this poster is available on the Publications page of Olema’s website. Additional information can be found on the AACR (Free AACR Whitepaper) Annual Meeting website, including abstracts.

About OP-3136
OP-3136 is a novel, orally available small molecule that potently and selectively inhibits lysine acetyltransferase 6 (KAT6), an epigenetic target that is dysregulated in breast and other cancers. In preclinical studies, OP-3136 has demonstrated significant anti-proliferative activity in ER+ breast cancer models and is combinable and synergistic with endocrine therapies, including palazestrant and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The Investigational New Drug (IND) application for OP-3136 was cleared by the U.S. Food and Drug Administration (FDA) in December 2024 and patients are currently enrolling in the Phase 1 clinical trial.

On April 25, 2025 Precision Biologics, Inc. reported preclinical development and characterization of a novel ADC using its anti-core 2 O-glycans anti-human carcinoma mAb PB-223 will be presented in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, on April 29th, 2025, McCormick Place Convention Center, Chicago, IL, USA (Press release, Precision Biologics, APR 25, 2025, View Source [SID1234652165]).

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Poster title: Development and characterization of an antibody-drug conjugate (ADC) utilizing PB-223, a novel monoclonal antibody (mAb) specifically targeting core 2 O-glycans on human carcinomas

The presentation of the poster will be made in person on the following date and location:

April 29th, 2025, 9am-12pm

McCormick Place Convention Center, Chicago, IL, USA

Session Title: Antibodies and Antibody-Drug Conjugates

Poster Section 36

Abstract Control Number 2878

BACKGROUND:

Antibody-drug conjugates (ADCs) represent a cutting-edge approach in cancer therapy. The three essential components of an ADC include: the mAb, the linker, and the cytotoxic payload. The mAb in current ADCs is usually designated to target specific tumor-associated antigens that are overexpressed on the surface of cancer cells.

Our ADC contains the following components:

The mAb: We used PB-223, an innovative mAb developed through affinity maturation of mAb NEO-102 (Ensituximab), a chimeric human IgG1 mAb that targets truncated core 2 O-glycans, specifically expressed by cancer cells and not by healthy tissues. The binding affinity of PB-223 for its target was improved, compared to NEO-102, by optimizing its VH and VL sequences through Fast Screening for Expression Biophysical Properties and Affinity. PB-223 demonstrated a binding affinity (KD) at least 4-fold lower than NEO-102, indicating stronger tumor binding. An immunohistochemistry analysis also revealed that PB-223 binds to a wider spectrum of tumor tissues compared to NEO-102, including not only colorectal, and pancreatic cancer, but also triple negative breast, prostate, kidney, head and neck, liver, and bladder cancer. Further experiments show PB-223 does not bind to normal tissues and that it can be internalized into human cancer cell lines expressing its target.
The payload: Monomethyl auristatin E (MMAE) was used as payload. MMAE is a potent antimitotic agent that inhibits cell division by blocking the polymerization of tubulin and is the most common ADC payload used to be linked to antibodies in clinical development for oncologic applications.
The linker: mc-vc-PABc was used as linker. PB-223 was conjugated to the linker-payload through a cysteine-based conjugation method.
STUDY PRESENTED AT AACR (Free AACR Whitepaper) 2025:

After development of the ADC we proceeded with its characterization, evaluating the following features:

DAR: The drug-to-antibody ratio (DAR) is crucial to predict the efficacy and safety of ADCs. It is generally believed that a DAR between 2 and 4 is the best choice for ADC drugs. Higher DAR may disrupt the pharmacokinetic properties of ADCs, while lower DAR significantly negatively affects the potency of ADCs. We developed three ADCs: PB-MMAE-2, PB-MMAE-5 and PB-MMAE-6. The DAR for these ADCs was 3.72, 3.92 and 4.15, respectively.
Binding of ADCs to cancer cells expressing core 2 O-glycans: flow cytometry was used for binding assessment of three ADC clones using the human ovarian cancer cell line OV-90 as the target. All three ADCs exhibit similar binding affinity to OV-90 compared to PB-223.
Killing of cancer cells: We evaluated the ability of all three ADC clones to kill OV-90 cells. All three ADCs effectively killed OV-90 cells (80% of cells were dead 5 days after treatment). We then chose one ADC clone, PB-MMAE-5, to test its ability to kill additional human cancer cell lines. Preliminary results show that PB-MMAE-5 can kill human prostate, triple positive and triple negative breast, lung, colon, pancreatic cancer cell lines.
Safety in vivo: We chose the ADC clone PB-MMAE-5 to test its toxicity in rats. The ADC PB-vcMMAE-5 in rats was administered intravenously at a concentration of 2.3 mg/kg as single dose. Animal body weight was measured at different time points until 14 days after ADC administration. The ADC PB-vcMMAE-5 was well tolerated in rats. No sign of distress nor loss of body weight were observed after administration.
Stability in human plasma: Stability of the ADC PB-vcMMAE-5 was evaluated in human plasma. PB-vcMMAE-5 ADC was incubated with male and female human plasma at concentration of 50 µg/mL and 100 µg/mL. Concentration in human plasma was detected by ELISA at 0h, 24h (1 day), 48h (2 days), 96h (4 days), 168h (7 days), 240h (10 days), 336h (14 days). The ADC was stable in human plasma (after 14 days, mean residual rate of PB-vcMMAE-5 ADC in human plasma was 23% for ADC at 100 µg/mL and 22% for ADC at 50 µg/mL).
Efficacy in vivo: The efficacy of the ADC PB-vcMMAE-5 was assessed in OV-90 subcutaneous xenograft model established in NOD-SCID mice. The ADC PB-vcMMAE-5 was administered intravenously at doses 1 mg/kg and 3 mg/kg, once per week for three weeks. Preliminary data suggest that PB-vcMMAE-5 exhibits anti-tumor activity in the NOD-SCID mice tumor model. Two days after the second dose of PB-vcMMAE-5 at 3mg/kg, treated mice showed a significant reduction in tumor volume compared to mice treated with an 1mg/kg dose of PB-vcMMAE-5, PBS or payload alone.
Findings from this study showed that PB-vcMMAE-5 can kill cancer cells expressing PB-223’s target, is not toxic, is effective in vivo, and is stable in human plasma, suggesting that PB-vcMMAE-5 has promising potential as a therapeutic option for a range of human malignancies expressing core 2 O-glycans.

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.