On April 29, 2025 AbCellera (Nasdaq: ABCL) reported new data on its PSMA x CD3 T-cell engagers (TCEs), presented as a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)Ⓡ (AACR) (Free AACR Whitepaper) 116th Annual Meeting at the McCormick Place Convention Center in Chicago, Illinois, taking place April 25 to 30, 2025 (Press release, AbCellera, APR 29, 2025, View Source [SID1234652344]).

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Targeting prostate-specific membrane antigen (PSMA) with a CD3 TCE could provide an effective treatment option for metastatic castration-resistant prostate cancer (mCRPC). In its poster presentation at AACR (Free AACR Whitepaper), AbCellera demonstrated that its PSMA x CD3 TCEs show promising preclinical activity, including:

Potent in vitro tumor-cell killing, with one molecule showing ~10x higher EC50 than benchmark
Sustained in vitro activity across four rounds of serial T-cell killing
Preclinical in vivo efficacy, with significant tumor growth inhibition in a xenograft mouse model
Potential for enhanced potency when combined with costimulatory PSMA x CD28 bispecifics
"The preclinical data package presented at AACR (Free AACR Whitepaper) is the first demonstration that our novel CD3-binders can be used to generate molecules with potent anti-tumor efficacy in vivo," said Adam Clarke, Ph.D., SVP, Discovery at AbCellera. "The poster underscores the strength of our TCE platform strategy, which is to combine diverse CD3- and tumor-binding antibodies and use empirical testing to engineer optimized therapeutic candidates. In addition, the data strongly support the use of costimulation to further increase anti-tumor activity."

On April 29, 2025 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients, reported that five presentations of clinical and preclinical data from the Company’s induced pluripotent stem cell (iPSC) product platform will be featured at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 28th Annual Meeting, being held in New Orleans, Louisiana on May 13-17, 2025 (Press release, Fate Therapeutics, APR 29, 2025, View Source [SID1234652308]).

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The Company has been selected to deliver an oral presentation on the translational data from its Phase 1 clinical trial of FT522, an off-the-shelf, CD19-targeted CAR NK cell product candidate, in patients with relapsed / refractory B-cell lymphoma (BCL) (NCT05950334). FT522 is the first product candidate to incorporate Alloimmune Defense Receptor (ADR) technology, which is designed to reduce or eliminate the need for administration of conditioning chemotherapy to patients receiving cell therapies. In addition, the Company will highlight preclinical data from its off-the-shelf, iPSC-derived, CAR T-cell product platform across autoimmune disease, hematological malignancy and solid tumor indications.

Accepted abstracts are available on the ASGCT (Free ASGCT Whitepaper) Annual Meeting website. Presentation details are as follows:

Oral Presentation

Phase 1 Translational Assessment of an Off-The-Shelf CAR NK Cell Armed with Alloimmune Defense Technology for Conditioning-free Therapy

Session: Innovation in Alternative Cell Therapy Sources
Location: Room 391-392
Presentation Date / Time: Saturday, May 17, 2025, 11:00 AM CT

Poster Presentations

Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy

Poster Number: 758
Presentation Date / Time: Tuesday, May 13, 2025, 6:00 PM CT

Targeting UPAR With Multiplexed-Engineered iPSC-Derived CAR T Cells to Reverse Age- and Insult-Related Fibrotic Disease

Poster Number: 789
Presentation Date / Time: Tuesday, May 13, 2025, 6:00 PM CT

Next-Generation Off-the-Shelf CAR T-Cell Therapies for Conditioning-Free Treatment of a Broad Spectrum of Autoimmune Diseases and Hematologic Malignancies

Poster Number: 1259
Presentation Date / Time: Wednesday, May 14, 2025, 5:30 PM CT

FT836, a Novel MICA/B-targeting CAR T-cell Therapy Engineered to Eliminate the Need for Conditioning Chemotherapy with Broad Activity Across Solid Tumor Indications

Poster Number: 1229
Presentation Date / Time: Wednesday, May 14, 2025, 5:30 PM CT

On April 29, 2025 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported findings on an exposure-outcome analysis of its innate cell engager (ICE) AFM24, in patients with advanced or metastatic non-small cell lung cancer (NSCLC) in a poster session at the 2025 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Affimed, APR 29, 2025, View Source [SID1234652329]).

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The analysis is based on post-hoc exposure-response data from 72 NSCLC patients treated with 480 mg of AFM24 monotherapy or a combination of AFM24 with atezolizumab. For all patients, trough levels over time were used to calculate the patient’s mean exposure to AFM24. Patients were then split into high and low AFM24 exposure groups for the analysis using the respective median as a cut-off.

Key Findings from the Exposure-Response Analysis

Objective Response Rate (ORR): 33.3% in the high-exposure group vs. 5.6% in the low-exposure group (p=0.0059)
Disease Control Rate (DCR): 83.3% vs. 58.3% (p=0.0367)
Median Progression-Free Survival (mPFS): 7.33 vs. 2.86 months
Overall Survival (OS): Not yet mature in the high-exposure group vs. 13 months in the low-exposure group
A quartile analysis further confirmed the exposure-efficacy relationship, showing a stepwise increase in ORR from 0% in the lowest quartile to 50% in the highest. Subgroup analysis of 55 patients treated with AFM24 plus atezolizumab showed consistent results: 37.04% ORR in the high-exposure group vs. 7.14% in the low group. Importantly, higher exposure was not associated with an increased rate of more serious or severe adverse events.

"Advanced NSCLC is a devastating disease and remains an area of high unmet need," said Andreas Harstrick, MD, Chief Medical Officer of Affimed. "These findings strengthen our clinical rationale for dose optimization and highlight the potential of AFM24 – particularly in combination with atezolizumab – as a novel, chemotherapy-free, immunotherapy-based treatment approach. Importantly, the data suggest that achieving higher drug exposure early in treatment may prevent rapid disease progression."

Further Development

Pharmacokinetic (PK) modeling indicates that a 720 mg weekly dose of AFM24—previously established as safe—achieves target exposure levels by the second week of treatment that correspond to the high exposure group in the post-hoc analysis. Based on these findings, Affimed will include the 720 mg dose moving forward to optimize clinical benefit and reduce early progression risk.

"These data provide compelling evidence that higher exposure may translate to better outcomes in patients with advanced NSCLC," Dr. Harstrick added. "With dose optimization in hand, we are positioned to advance AFM24 in its potential to deliver durable benefit in a difficult-to-treat patient population."

Conclusions

The data show a strong correlation between exposure and clinical outcome with a significantly increased risk for early tumor progression in the low exposure group. PK modeling suggests that a dose of 720 mg AFM24 weekly will result in exposure levels exceeding the cutoff for the high exposure group as early as week two. The 720 mg dose, which has already been established as safe in the phase 1 trial, will be used in future AFM24 studies.

More details about the programs for the AACR (Free AACR Whitepaper) Annual Meeting 2025 are available online at AACR (Free AACR Whitepaper) Annual Meeting 2025 | Meetings | AACR (Free AACR Whitepaper).

About AFM24
AFM24 is a tetravalent, bispecific ICE that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

On April 29, 2025 Bayer reported initiation of a Phase I clinical trial with 225Ac-GPC3 (BAY 3547926), an investigational targeted alpha radiopharmaceutical being developed to treat tumors expressing Glypican-3 (GPC3) in patients with advanced hepatocellular carcinoma (HCC) (Press release, Bayer, APR 29, 2025, View Source [SID1234652345]). Oncofetal protein GPC3 is a membrane-associated proteoglycan which is overexpressed in 70-75% of HCC lesions making it an attractive target for targeted radionuclide therapy.1,2 The first-in-human, dose escalation study (NCT06764316) will evaluate the safety, tolerability and preliminary efficacy of BAY 3547926 alone, and as a combination therapy in patients with advanced HCC.

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"Hepatocellular carcinoma continues to be a devastating disease for millions of patients and a pressing unmet need in cancer care. The launch of the Phase I trial using the 225Ac-GPC3 radionuclide therapy marks an important milestone in our commitment to develop new medicines targeting cancer cells with high effect size and precision to improve the lives of people living with cancer," said Dominik Ruettinger, M.D., Ph.D., Global Head of Research and Early Development for Oncology at Bayer’s Pharmaceuticals Division. "Through continued research innovation we can unlock the full potential of targeted alpha therapies which is an emerging class of targeted radionuclide therapy and a strategic focus area for Bayer’s precision oncology development portfolio."

Liver cancer, including hepatocellular carcinoma, is the third leading cause of cancer-related deaths in the world with almost 900,000 new cases annually.3 It is the most rapidly growing cause of cancer deaths in the US accounting for approximately 2% of new cases and 5% of cancer deaths.4 Despite recent scientific advancements, many doctors are not satisfied with the therapeutic benefits from the currently available treatments.

Targeted alpha therapy (TAT) has the potential to address high unmet medical need across various cancer types. Bayer’s growing TAT portfolio combines alpha particle-emitting radionuclides with different targeting moieties. 225Ac-GPC3 is the third TAT program in clinical development and the first investigational targeted radiopharmaceutical for Bayer in HCC. The newly disclosed targeted alpha conjugate joins 225Ac-Pelgifatamab and 225Ac-PSMA-Trillium, which are currently in Phase I clinical trials in patients with advanced metastatic castration resistant prostate cancer.

On April 28, 2025 Bayer introduced 225Ac-GPC3 in an oral presentation during the "New Drugs on the Horizon" session at the AACR (Free AACR Whitepaper) (American Association of Cancer Research) Annual Meeting, showcasing preclinical characterization of the asset including the low uptake and fast clearance from normal organs as well as induction of tumor regression in in vivo models. Recognition in this special symposium highlights the company’s commitment for precision oncology development portfolio.

1

Kolluri A and Ho M (2019), The Role of Glypican-3 in Regulating Wnt, YAP, and Hedgehog in Liver Cancer. Front. Oncol. 9:708. doi: 10.3389/fonc.2019.00708.
2

Yongle Wu, Hui Liu, Huiguo Ding, GPC-3 in hepatocellular carcinoma: current perspectives, Journal of Hepatocellular Carcinoma 2016:3, 63-67.
3

Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, Freddie Bray BSc, MSc, PhD; Mathieu Laversanne MSc; Hyuna Sung PhD; Jacques Ferlay ME; Rebecca L. Siegel MPH; Isabelle Soerjomataram MD, MSc, PhD; Ahmedin Jemal DVM, PhD.
4

SEER Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. National Cancer Institute. Bethesda, MD, View Source

About BAY 3547926
BAY 3547926 is an investigational targeted alpha radiopharmaceutical being developed to treat tumors expressing Glypican-3 (GPC3) in patients with advanced hepatocellular carcinoma (HCC). It is composed of a GPC3 targeting high affinity antibody radiolabeled with actinium-225 (225Ac). 225Ac-GPC3 delivers highly potent alpha-particles to the GPC3-expressing cancer cells, with the potential to inducing DNA double-strand breaks, reducing cancer cell viability which may potentially cause anti-tumor activity.

About Targeted Alpha Therapy
Targeted alpha therapy (TAT) is an emerging class of radionuclide therapy that can be used against a variety of tumors. It delivers alpha particle radiation directly to the tumor inside the body, either via its bone-seeking property (radium-223) or by combining alpha radionuclides, such as actinium-225, with specific targeting moieties.

Actinium-225 is an alpha particle–emitting radionuclide with a 9.9-day half-life. Alpha particles deposit highly ionizing radiation over a short range. This localized delivery of the radioactive payload induces irreparable DNA double-strand breaks, often resulting in cell death. At the same time, because the energy travels a short range, damage to nearby normal tissues is much reduced.

On April 29, 2025 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators have been selected to present at the upcoming American Society of Gene and Cell Therapy’s (ASGCT) (Free ASGCT Whitepaper) 28th Annual Meeting being held May 13-17, 2025 in New Orleans, Louisiana (Press release, Genprex, APR 29, 2025, View Source [SID1234652309]). The collaborators will present positive preclinical data and research from studies of GPX-002, the Company’s diabetes gene therapy drug candidate.

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"We are proud of the preclinical data supporting our novel gene therapy program for diabetes, and we believe selection to present our program at one of the premier events in cell and gene therapy provides another point of validation for our diabetes program," said Ryan Confer, President and Chief Executive Officer at Genprex. "We look forward to sharing our GPX-002 data with industry leaders engaged in advancing the latest scientific research and new technologies."

The oral presentation details for the Genprex-supported abstract:

Abstract Title: Immune Modulation Sustains Alpha Cell Reprogramming and Mitigates Immune Responses to AAV in a Diabetic Non-Human Primate Model

Session Title: Challenges in Immunological Responses to Therapeutic Interventions

Presenter: Hannah Rinehardt, MD, University of Pittsburgh Medical Center

Presentation Date: May 16, 2025

Presentation Time: 4:15 – 4:30 p.m. CT

Location: Room 278-282

The featured Genprex-supported abstract to be presented for oral presentation at the ASGCT (Free ASGCT Whitepaper) 28th Annual Meeting:

Gene therapy using recombinant adeno-associated virus (rAAV) offers a promising opportunity for curative therapy in diabetes mellitus. Retrograde intraductal infusion of rAAV6 to deliver Pdx1 and MafA, converting alpha cells into beta-like cells that secrete insulin physiologically, reverses diabetes in mouse models. Little is known about the direct infusion of AAV into the pancreatic duct for gene therapy in non-human primates (NHPs). In clinical trials, anti-viral immunity to AAV can be a barrier to successful gene therapy. Researchers evaluated the immune response to direct infusion of rAAV into the pancreatic duct of NHPs with streptozotocin-induced diabetes and evaluated how to best manage immune responses.

Diabetes was induced with streptozotocin (STZ) in cynomolgus macaques. NHPs received retrograde intraductal infusion of rAAV via laparotomy for precise delivery to the pancreas. rAAV capsids were chosen based on tropism for endocrine cells, and pre-existing neutralizing antibody titers (NAbs) were negative. Blood work including serum C peptide and IV glucose tolerance tests were serially obtained to monitor therapeutic efficacy. Immune response monitoring was performed for up to 4 months post-infusion and included serial NAbs, ELISpot assays, and immunophenotyping. Pancreatic tissues were analyzed using IHC and RNA-scope for beta cell markers, as well as single-cell RNA transcriptomics.

One-month post-infusion, NHPs showed improved glucose tolerance and reduced insulin requirements. The AAV6 capsid with endocrine-specific promoters driving Pdx1 and MafA showed durable effects. ELISpot-positive cytotoxic T cells and neutralizing antibodies developed when steroids were absent. With steroid-sparing regimens, pancreatic B and T lymphocyte populations were noted on scRNA sequencing. Temporary immunosuppression (IS), using a combination of rituximab, rapamycin, and steroids, for a 3-month course is largely effective at preventing anti-viral immunity. Despite complete IS discontinuation at 3 months post-infusion, meaningful anti-viral immune response was not mounted up to one month after IS withdrawal as evidenced by low NAb titers and negative ELISpot analysis. Additionally, rAAV gene therapy in these animals remained effective and glucose tolerance continued improving in the absence of immunosuppression.

In conclusion, researchers developed a novel rAAV gene therapy approach and demonstrated that infusion of rAAV directly into the pancreatic duct of NHPs induces an anti-viral immune response. The anti-viral immune response in NHPs can be largely prevented by administration of a multi-agent IS and can allow for sustained therapeutic effects.

About GPX-002

GPX-002, which has been exclusively licensed from the University of Pittsburgh, is currently being developed using the same construct for the treatment of both Type 1 diabetes (T1D) and Type 2 diabetes (T2D). The same general novel approach is used in each of T1D and T2D whereby an adeno-associated virus (AAV) vector containing the Pdx1 and MafA genes is administered directly into the pancreatic duct. In humans, this can be done with a routine endoscopy procedure. In T1D, GPX-002 is designed to work by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body’s immune system. In vivo, preclinical studies show that GPX-002 restored normal blood glucose levels for an extended period of time in T1D mouse models. In T2D, where autoimmunity is not at play, GPX-002 is believed to rejuvenate and replenish exhausted beta cells.