On April 28, 2025 Attivare Therapeutics, Inc., an innovative oncology company focused on the development of its ATTimmune biomaterial scaffold cancer therapies to treat patients across a range of solid and liquid tumors with significant unmet medical needs, reported it will present preclinical data for its novel ATT-01 and ATT-02 therapeutics in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Attivare Therapeutics, APR 28, 2025, View Source [SID1234652290]).

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ATT-01 uses its ATTimmune platform technology, a silica-based, biodegradable scaffold (mesoporous silica rod, MSR), loaded with GM-CSF and CpG to induce differentiation of AML blasts in vitro, a significant vaccine-like T cell response, and durable remission in syngeneic murine models of AML.

Intratumoral ATT-02 combines the ATTimmune scaffold coupled with Interleukin 12 (IL-12) to show potent anti-tumor immunity compared to IL-12 alone in multiple single tumor syngeneic models and abscopal syngeneic models. Complete responses were observed in two colon carcinoma models (localized and abscopal) after a single dose of ATT-02. Of interest, ATTimmune alone had anti-tumor activity with delayed tumor progression and in vitro, shows a repolarization of macrophages to an immunogenic phenotype capable of driving T cell activation with addition of IL-12 enhances this effect.

"We are excited to present our preclinical data for ATT-01 and ATT-02 at the AACR (Free AACR Whitepaper) Annual Meeting," said David Sherris, President and Chief Executive Officer of Attivare Therapeutics. "Here, we present ATTimmune, a novel silica-based platform to deliver potent immune agonists to combat cancer. ATTimmune has advantages over other drug delivery technologies as it can bind a variety of therapeutic agents with a high payload, be it biologics, small molecules, gene therapy or even cellular technologies to its surface without alteration of the therapeutic agents. ATTimmune controllably releases drug over time within a 21-day period. Due to size, ATTimmune remains at its injected location thereby keeping drug where activity is required, as in the tumor microenvironment. As such, ATTimmune has the capability of reducing or eliminating toxicity for drugs having systemic toxicity."

Details of the poster presentations at AACR (Free AACR Whitepaper) 2025 are as follows:

Title: Delivery of CpG and GM-CSF in a novel silica-based scaffold leads differentiation of AML blasts and T cell-dependent immunity in syngeneic AML tumor models

Abstract Presentation Number: 3467
Session Title: Local Treatments, Novel Tools, and Delivery Systems to Manipulate Tumor Immunity
Session Date and Time: Monday, April 28, from 2 p.m. to 5 p.m. CT (3 p.m. to 6 p.m. ET)
Location: Poster Section 37
Poster Board Number 6
Title: A single intratumoral injection of Il-12 bound to mesoporous silica rods generates effective anti-tumor immune responses and tumor growth control in multiple syngeneic tumor models

Abstract Presentation Number: 3476
Session Title: Local Treatments, Novel Tools, and Delivery Systems to Manipulate Tumor Immunity
Session Date and Time: Monday, April 28, from 2 p.m. to 5 p.m. CT (3 p.m. to 6 p.m. ET)
Location: Poster Section 37
Poster Board Number 15

On April 28, 2025 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported the publication of an abstract with preclinical data from their cytoDRiVE platform for poster presentation at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting 2025 (Press release, Obsidian Therapeutics, APR 28, 2025, View Source [SID1234652289]).

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Obsidian will present novel applications of its cytoDRiVE platform, demonstrating the breadth and versatility of their regulation technology. To date, cytoDRiVE technology has been used to successfully regulate the timing and level of several different classes of therapeutic protein via fusion to drug-responsive domains (DRDs).1 In OBX-115, Obsidian’s lead clinical TIL program which has demonstrated promising activity in patients with ICI-resistant advanced melanoma2, this technology enables regulation of membrane-bound IL15 using the small-molecule drug acetazolamide.

The poster for abstract AMA30 expands beyond the direct DRD-fusion approach leveraged to-date, providing proof-of-concept for a novel approach whereby regulation of an artificial transcription factor is used to enable gene-ON and gene-OFF states with ligand binding. This approach unlocks numerous additional applications for cytoDRiVE, including the ability to regulate secreted proteins and expression of mRNA or siRNA. These capabilities become important in the context of gene and cell therapies where precise and variable genetic control is needed to manage disease, and where repeat dosing of other complex biologics is challenging.

Details of the poster presentation are as follows:

Title: Drug-responsive domains coupled with cognate small-molecule ligands drive synthetic gene-ON or -OFF circuits to regulate expression of therapeutic proteins (Abstract AMA30)
Presenting Author: Michael Gallo (Obsidian Therapeutics)
Poster: Tuesday, May 13, 6:00-7:30pm CT
Abstract: AMA30
1 Inniss et. al. Commun Biol 2025
2 Chesney, ASCO (Free ASCO Whitepaper) 2025

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 28, 2025 Ankyra Therapeutics, a leading clinical-stage company developing anchored drug conjugates for the treatment of cancer, reported preliminary data highlighting the safety and biologic activity of their lead asset, tolododekin alfa (ANK-101), an anchored interleukin-12 (IL-12) drug conjugate (Press release, Ankyra Therapeutics, APR 28, 2025, View Source [SID1234652288]). The data was derived from Part 1 of the first-in-human (FIH) ANCHOR Phase 1 clinical trial. The study was designed to evaluate the safety and feasibility of tolododekin alfa, as monotherapy in patients with advanced solid tumors. Dr. Howard Kaufman, Ankyra President and CEO stated that "We are extremely pleased with the data which provided support for the potential of the anchored drug conjugate platform." He added "The study demonstrates for the first time that IL-12 can be delivered to tumors at therapeutic doses higher than previously achievable without systemic toxicity." Systemic delivery of IL-12 has been evaluated in previous clinical studies, but development was halted after a maximum tolerated dose of 500 ng/kg prevented further dose escalation of IL-12 in cancer patients. Dr. Joe Elassal, Ankyra Chief Medical Officer added that tolododekin alfa "Phase 1 data are encouraging and we have seen that IL-12 anchoring has resulted in 6-fold higher local IL-12 delivery to established cancers compared with what has been achieved with systemic administration." Furthermore, biomarker analysis of tumor-treated biopsies showed increased CD8+ T cell infiltration and induction of local PD-L1 expression. Dr. Elassal added "The high levels of PD-L1 seen provide strong justification for our expansion cohort combining tolododekin alfa with immune checkpoint blockade." Ankyra reports that on March 25, 2025 the first patient with advanced cutaneous squamous cell carcinoma was treated with a combination of tolododekin-alfa and Regeneron’s PD-1 inhibitor, Libtayo (cemiplimab), in an expansion cohort to the current Phase 1 trial.

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Results from Part one of the Phase 1 FIH study are being presented on Monday, April 28, 2025 at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL.

Abstract Title: Results of a first-in-human phase 1 trial of anchored IL-12 drug conjugate (ANK-101).

Session Title: Phase 0 and Phase I Clinical Trials
Session Start: 4/28/2025 9:00:00 AM
Session End: 4/28/2025 12:00:00 PM
Location: Poster Section 49
Poster Board Number: 18
Abstract Presentation Number: CT039
The poster will be available on the publications section of Ankyra’s website after the meeting at View Source

Key Study Findings

Fifteen (15) patients with metastatic solid tumors who had progressed on standard therapy and had accessible lesions for injection were enrolled across four study sites in the U.S. and Canada
Primary tumor histology included melanoma (n=7), head and neck cancer (n=4), breast cancer (n=2), bladder cancer (n=1), and apocrine adenocarcinoma (n=1)
ANK-101 monotherapy was well-tolerated at doses up to 250 µg/mL with no DLTs or Grade 3 or greater treatment-related treatment-emergent adverse events (TEAEs)
Highly efficient tumor retention with low (generally <1%) systemic IL-12-ABP
ANK-101 induced CD8+ T cell recruitment, PD-L1 expression, and inflammatory gene signatures consistent with biologic IL-12 activity
Initial results suggest clinical activity with 2 PRs and a disease control rate of 80% by modified RECIST v1.1
About Tolododekin alfa (ANK-101)
Tolododekin alfa (ANK-101) is an anchored drug conjugate composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local delivery of functional IL-12 to the tumor microenvironment where it remains biologically active for several weeks but does not diffuse into the systemic circulation, thereby avoiding systemic toxicity. Treatment with ANK-101 in animal models has been associated with recruitment and retention of CD8+ T cells, NK cells and M1 macrophages activating innate and adaptive anti-tumor immunity. ANK-101 is being evaluated for the treatment of advanced solid tumors alone and in combination with anti-PD-1 agents. The first-in-human, open-label clinical trial of ANK-101 as a monotherapy (NCT:06171750) consists of a dose escalation portion that will evaluate the safety and tolerability of ANK-101, followed by dose expansion cohorts. Additional clinical trials are being planned in different cancer types.

ANK-101 will be prominently featured on an upcoming documentary "The Cancer Pioneers" as part of the Public Broadcasting System (PBS) series "Shelter Me". The program will air nationally on local PBS television stations on May 1, 2025 and more information can be found at View Source

On April 28, 2025 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that clinical data on neratinib were presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Puma Biotechnology, APR 28, 2025, View Source [SID1234652287]). The AACR (Free AACR Whitepaper) Annual Meeting is currently taking place at the McCormick Place in Chicago, Illinois. The poster is entitled, "CT071: Phase I trial of trastuzumab deruxtecan in combination with neratinib in solid tumors with HER2 alterations (NCI 10495)." Andrew A. Davis, Assistant Professor at Washington University School of Medicine, presented the poster during Session PO.CT01.01 – First-in-Human Phase I Clinical Trials 1.

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NCI 10495 is sponsored by the National Cancer Institute, part of National Institutes of Health, and conducted in the NCI funded Experimental Therapeutics Clinical Trials Network (ETCTN). This open label, multi-center, Phase I clinical trial (NCT05372614) enrolled 20 patients in three cohorts treated with three increasing dose levels, or a 3+3 trial design, to evaluate the safety and tolerability of trastuzumab deruxtecan (T-DXd or ENHERTU) in combination with neratinib (NERLYNX). Eligible patients had advanced solid tumors with HER2 immunohistochemistry 3+ (IHC3+), HER2 amplification identified by in situ hybridization or next-generation sequencing, or an activating HER2 mutation. Prior treatment with trastuzumab deruxtecan was not allowed. The dose of trastuzumab deruxtecan was fixed at 5.4 mg/kg. The three dose levels (DLs) for neratinib all started at 120 mg daily for the first week. DL1 remained at 120 mg daily throughout the course of treatment, DL2 escalated to 160 mg daily in week 2 and 200 mg by week 3, and DL3 escalated to 160 mg in week 2 and 240 mg by week 3. The primary endpoints were the determination of the dose-limiting toxicities (DLTs) during the first two cycles of treatment (42 days) and the determination of the recommended Phase II dose of the combination of trastuzumab deruxtecan and neratinib.

Twenty patients received study treatment (DL1 N=7, DL2 N=4, and DL3 N=9). The most common treatment-emergent adverse events of any grade included nausea (N=15, 75%), diarrhea (N=15, 75%), fatigue (N=13, 65%), and hypokalemia (N=11, 55%). Grade 3 treatment-emergent adverse events that occurred in more than 2 patients included anemia (N=6, 30%), diarrhea (N=4, 20%), and hypokalemia (N=3, 15%). The only Grade 4 treatment-related adverse event was neutropenia that occurred in 1 patient (5%). One DLT (acute kidney injury) was observed at DL1, 0 DLTs were observed in DL2, and 1 DLT was observed (fatigue leading to early drug discontinuation) at DL3. Three patients developed Grade 1 pneumonitis or interstitial lung disease (ILD), 2 at DL1 and 1 at DL3. The proportion of reported treatment-emergent adverse events was lower at higher dose levels.

Of 15 response-evaluable patients by RECIST v1.1, 4 patients had a partial response (PR), including patients with gastroesophageal (N=2, one HER2 IHC 3+ and one HER2 mutated), pancreatic (N=1, IHC 3+), and ovarian (N=1, IHC 3+; unconfirmed response) cancers. Notably, 3 of 5 patients with advanced pancreatic cancer were observed to have tumor regression (1 PR for 13+ cycles, 2 with stable disease consisting of one patient with -29.4% tumor regression for 9 cycles and one patient with -13.3% tumor regression for 8 cycles).

Dose level 3, which consisted of trastuzumab deruxtecan at 5.4 mg/kg and neratinib at 120 mg in week 1, 160 mg week 2, and 240 mg week 3 onward, was selected as the recommended Phase II dose. Part 2 of this study, which consists of a pharmacodynamic evaluation of trastuzumab deruxtecan (5.4 mg/kg) and neratinib (RPD2) in 12 patients, opened to enrollment in March 2025. Patients with any advanced solid tumor and HER2 amplification/overexpression or a HER2 mutation will be enrolled.

"Neratinib and trastuzumab deruxtecan showed impressive combination activity in preclinical models of HER2-mutated breast cancers, which prompted evaluation of the combination in this first-in-human clinical trial. I am pleased to report that the combination not only had a manageable safety profile, but we also observed early signs of efficacy across a variety of HER2-altered tumors," said Dr. Davis.

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, added, "We are pleased with the tolerability and potentially promising signals of efficacy of neratinib in combination with trastuzumab deruxtecan, especially in hard-to-treat tumors including pancreatic cancer. We look forward to continued evaluation of this combination in the Phase II portion of this study."

NCI 10495 is also supported by Puma Biotechnology and Daiichi Sankyo, Inc. through Cooperative Research and Development Agreements with NCI.

Trastuzumab deruxtecan is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

On April 28, 2025 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported the acceptance of an abstract for an oral presentation at the upcoming American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting taking place May 13-17, 2025, in New Orleans, LA (Press release, Adicet Bio, APR 28, 2025, View Source [SID1234652286]).

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Details of the oral presentation are as follows:

Title: ADI-270, an Armored Allogeneic Anti-CD70 CAR γδ T Cell Therapy, Demonstrates Robust CAR-Directed and -Independent Anti-Tumor Activity Against Hematologic and Solid Tumor Models Compared to Conventional CAR αβ T Cells
Session Name: Engineered Immune Effector Cells for Solid Tumors
Presenting Author: Melinda Au
Date and Time: May 17, 2025; 11:45 a.m. – 12:00 p.m. CT