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Alector Reports Third Quarter 2025 Financial Results and Provides Business Update

On November 6, 2025 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company focused on developing therapies to counteract the devastating progression of neurodegeneration, reported third quarter 2025 financial results and recent portfolio and business updates. As of September 30, 2025, Alector’s cash, cash equivalents, and investments totaled $291.1 million.

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"We are well-resourced to advance our portfolio of innovative drug candidates for the treatment of neurodegenerative diseases, with a sharpened focus on our differentiated Alector Brain Carrier (ABC) platform," said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. "ABC represents an important driver of innovation, with the versatility to deliver antibodies, enzymes and nucleic acid to the brain. Our ABC-enabled programs have demonstrated robust brain penetration through peripheral dosing, favorable safety, and good pharmacokinetics. We are advancing AL137, our ABC-enabled anti-amyloid beta antibody, AL050, our ABC-enabled GCase enzyme replacement therapy, and ADP064, our ABC-enabled Tau siRNA, toward IND-enabling studies, with IND submissions targeted in 2026 and 2027."

Dr. Rosenthal continued, "Additionally, together with GSK, we continue to advance the Phase 2 PROGRESS-AD trial for nivisnebart (AL101), an investigational monoclonal antibody being studied for the treatment of Alzheimer’s disease. We remain on track for an independent interim analysis planned for the first half of 2026."

Recent Program Updates

Alector Brain Carrier: Preclinical and Research Pipeline

A key pillar of Alector’s focus is its proprietary blood-brain barrier (BBB) technology platform, Alector Brain Carrier (ABC). Built on the core design principles of versatility, tunability, and differentiated binding to a distinct region of the transferrin receptor (TfR), ABC is intended to support the targeted delivery of therapeutics to the brain and to optimize safety and efficacy. The platform’s tunable TfR binding affinities allow adjustment of binding strength and drug configuration to align with the needs of diverse therapeutic cargos, including antibodies, enzymes, and siRNA, aiming to achieve efficient transport across the BBB with the goal of balancing brain uptake and safety.

AL137

Alector has selected lead candidate AL137 for its ABC-enabled anti-amyloid beta (Aβ) antibody in Alzheimer’s disease (AD) and is advancing it toward investigational new drug (IND)-enabling studies. The company is targeting an IND filing for AL137 in 2026.

AL137 is engineered for optimal brain uptake, potency, safety, and convenience. This candidate features a high-affinity, humanized antibody that selectively binds PyroGlu3, a validated epitope on the toxic form of Aβ found in plaques, a fully active effector function that enables maximal recruitment of myeloid cells to remove plaques, and Alector’s proprietary ABC with tuned affinity and binding epitope designed to facilitate brain penetration and plaque removal while minimizing hematologic adverse effects. In preclinical studies to date, AL137 has demonstrated robust brain penetration at low doses, supporting the potential for low dose, subcutaneous administration.
AL050

Alector has selected lead candidate AL050 for its ABC-enabled glucocerebrosidase (GCase) enzyme replacement therapy (ERT) in Parkinson’s disease (PD) and is advancing the candidate toward IND-enabling studies. The company is targeting submission of an IND application for AL050 in 2027.

AL050 is an ABC-enabled GCase ERT engineered to address the key challenges of enzyme replacement for the brain. It features an engineered GCase with improved activity and stability, a silenced effector function to maximize safety, and Alector’s tunable ABC with a TfR epitope and affinity designed to enhance delivery across the BBB. In preclinical studies to date, AL050 increased GCase activity in both rodents and NHPs and reduced toxic substrate accumulation in a rodent GBA disease model with no apparent hematologic findings, supporting its potential as a therapy for Parkinson’s disease and Lewy body dementia associated with GBA loss-of-function mutations.
ABC siRNA Platform

The company also continues to advance its ABC-enabled siRNA platform. The platform is designed for peripheral dosing, offering the potential for more convenient administration compared with traditional intrathecal or intracerebroventricular delivery, as well as homogeneous drug distribution throughout the brain. Current programs include Alector’s lead siRNA program, ADP064-ABC, an anti-tau siRNA for AD and other tauopathies, as well as ADP062-ABC, an alpha-synuclein siRNA for PD and eventually Lewy body dementia; and ADP065-ABC, an NLRP3 siRNA, for a range of neurodegenerative diseases.
Progranulin Programs (nivisnebart (AL101/GSK4527226) and latozinemab (AL001)) in Collaboration with GSK

Nivisnebart (AL101/GSK4527226)

The 76-week, global, randomized, double-blind, placebo-controlled PROGRESS-AD Phase 2 clinical trial of nivisnebart (AL101/GSK4527226) in early AD is ongoing, with enrollment completed in April 2025. An independent interim analysis is planned for the first half of 2026.

Nivisnebart is an investigational human monoclonal antibody (mAb) designed to block and internalize the sortilin receptor to elevate the concentrations of progranulin (PGRN) in the brain. It is distinct from latozinemab, with differentiated pharmacokinetic and pharmacodynamic properties that may make it suitable for the potential treatment of more prevalent neurodegenerative diseases.
Latozinemab

In October 2025, Alector and GSK announced topline results from the INFRONT-3 Phase 3 clinical trial of latozinemab for the potential treatment of frontotemporal dementia due to a GRN gene mutation (FTD-GRN). The study did not demonstrate clinical benefit. Based on these results, the open-label extension portion of the INFRONT-3 trial and the continuation study for latozinemab will be discontinued.
Corporate News

In October 2025, the company implemented a reduction in force of approximately 47% intended to focus the company’s resources on its highest-priority programs, to ensure continued progress across its portfolio, and extend cash runway through 2027.
Third Quarter 2025 Financial Results

Revenue. Collaboration revenue for the quarter ended September 30, 2025, was $3.3 million, compared to $15.3 million for the same period in 2024. The decrease was mainly due to the satisfaction of the performance obligation associated with the AL002 program and the latozinemab FTD-C9orf72 Phase 2 trial in the fourth quarter of 2024.

R&D Expenses. Total research and development expenses for the quarter ended September 30, 2025, were $29.4 million, compared to $48.0 million for the quarter ended September 30, 2024. The decrease was mainly due to a decrease in research and development expenses for the AL002 program as well as a decrease in personnel related costs as a result of the reductions in force.

G&A Expenses. Total general and administrative expenses for the quarter ended September 30, 2025, were $11.5 million, compared to $15.8 million for the quarter ended September 30, 2024. The decrease was mainly driven by the absence of impairment charges related to the right-of-use asset and leasehold improvements recognized in the third quarter of 2024. No comparable impairment occurred in the current period. Additionally, personnel-related costs declined as a result of the reductions in force.

Net Loss. For the quarter ended September 30, 2025, Alector reported a net loss of $34.7 million, or $0.34 per share, compared to a net loss of $42.2 million, or $0.43 net loss per share, for the same period in 2024.

Cash Position. Cash, cash equivalents, and investments were $291.1 million as of September 30, 2025. This includes approximately $14.7 million in net proceeds raised through the company’s at-the-market (ATM) equity offering in September. In October 2025, the company raised $5.3 million in ATM equity offerings. Management anticipates that its current cash position will be sufficient to fund Alector’s operations through 2027.

2025 Guidance. The company continues to anticipate collaboration revenue to be between $13 million and $18 million, total research and development expenses to be between $130 million and $140 million, and total general and administrative expenses to be between $55 million and $65 million.

(Press release, Alector, NOV 6, 2025, View Source [SID1234659548])

Transgene to Showcase Potential of Proprietary VacDesignR® Computational Tool to Optimize Individualized Therapeutic Cancer Vaccines

On November 6, 2025 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer reported it will present a poster on its proprietary VacDesignR computational tool at the upcoming ESMO (Free ESMO Whitepaper) AI & Digital Oncology 2025 conference, held in Berlin, Germany, from 12-14 November 2025.

The presentation will highlight how VacDesignR streamlines the design and production of recombinant Modified Vaccinia Ankara (MVA)-based vectors, enabling faster and more reliable manufacturing of individualized neoantigen therapeutic vaccines (INTV).
The individualized immunotherapies developed through the myvac platform, currently being evaluated in a Phase I/II clinical trial (NCT04183166), are based on an MVA viral vector and their design already leverages the VacDesignR tool.

Developed in-house, VacDesignR is a computational design engine that optimizes recombinant plasmid architecture for MVA vectors, a core component of Transgene’s myvac platform. By minimizing unwanted homologous recombination and intelligently selecting peptide sequences for cassette assembly, VacDesignR significantly improves production reliability and vector quality.

Future iterations of VacDesignR will incorporate AI-based components to further improve performance and scalability, supporting Transgene’s strategy to accelerate production timelines for individualized therapeutic vaccines, including its lead candidate TG4050 designed to treat HPV-negative head and neck cancers following surgery and adjuvant therapy.

"Participating at the first edition of the ESMO (Free ESMO Whitepaper) AI & Digital Oncology meeting highlights Transgene’s pioneering role in combining viral vector-based individualized cancer vaccines with its vaccine design tool to optimize product performance and redefine the future of oncology treatment", commented Maurizio Ceppi, Chief Scientific Officer of Transgene.

Title of the abstract: "VacDesignR: a computational tool to optimize viral-based individualized neoantigen therapeutic vaccine production"

Title of the poster: "VacDesignR: a tool for optimizing recombinant poxvirus vaccine production"

Poster and Abstract number: 385P
Session: Drug development
Date: November 12, 2025
Author: B. Grellier
The poster presentation will take place on November 12 at ESMO (Free ESMO Whitepaper)-AI conference and will be available that day on Transgene’s website.

VacDesignR is a computer-assisted method protected through patent and patent applications derived from WO2021/130210.

(Press release, Transgene, NOV 6, 2025, View Source [SID1234659484])

U.S. FDA Grants Orphan Drug Designation to Leukogene Therapeutics’ M2T-CD33 (LTI-214) for the Treatment of Acute Myeloid Leukemia

On November 5, 2025 Leukogene Therapeutics Inc. (LTI), a biopharmaceutical company developing next-generation immunotherapies for hematologic and other malignancies, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to the Company’s lead product candidate, M2T-CD33 (LTI-214), for the treatment of Acute Myeloid Leukemia (AML).

This designation underscores the significant unmet medical need for AML patients and recognizes the therapeutic potential of LTI-214 as a novel and differentiated approach for this aggressive blood cancer. The designation may provide LTI with a range of development incentives, including eligibility for tax credits on qualified clinical trial costs, waiver of certain FDA fees, and U.S. market exclusivity upon approval.

"We are honored that the FDA has recognized the therapeutic promise of LTI-214 by granting Orphan Drug Designation," said Dr. Sandeep Gupta, CEO of Leukogene. "AML remains one of the most challenging hematologic cancers, and outcomes for relapsed or refractory patients remain poor. The LTI-214 program embodies our commitment to advancing new immunotherapy approaches that are both potent and safer for patients. This designation represents an important step toward our goal of transforming the treatment paradigm for AML."

Nathan Dolloff, PhD, Founder and CSO of Leukogene stated, "This is an important step forward for Leukogene and the company’s Major Histocompatibility Complex Class II (MHCII) engager technology. The M2T platform is a completely new approach to cancer immunotherapy and the endorsement from FDA is a testament to its high impact potential."

(Press release, Leukogene Therapeutics, NOV 5, 2025, View Source [SID1234659495])

Adicet Bio Reports Third Quarter 2025 Financial Results and Provides Business Updates

On November 5, 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 financial results and operational highlights for the third quarter ended September 30, 2025.

"We were pleased to announce positive preliminary data last month from seven SLE and LN patients treated in our Phase 1 trial of ADI-001, underscoring its broad potential as a transformative, off-the-shelf, one-time therapy for autoimmune diseases. We are now preparing to discuss the trial design for a potentially pivotal study of ADI-001 with the FDA in the first quarter of 2026, with initiation targeted for the second quarter of 2026," said Chen Schor, President and Chief Executive Officer of Adicet Bio. "As part of our broader clinical strategy, we are also exploring the potential to reduce or eliminate the need for conditioning with a separate Phase 1 trial of ADI-001 in treatment-refractory RA patients. We are actively enrolling patients in our Phase 1 trial across LN, SLE, SSc, IIM, SPS and AAV patients, with a clinical update for LN, SLE and SSc expected in the first half of 2026."

Mr. Schor continued: "In addition, we are continuing to advance ADI-212, an optimized next-generation gene-edited and armored clinical candidate designed to target prostate specific membrane antigen, and expect to submit a regulatory filing for the mCRPC program in the first quarter of 2026 and share initial clinical data in the second half of 2026, subject to regulatory clearance. ADI-212 is designed to enhance potency in solid tumors and deliver multiple anti-tumor mechanisms of action to the tumor microenvironment. Supported by our recent capital raise in October, which extended our cash runway into the second half of 2027, we are well-positioned to continue clinical execution across our pipeline of differentiated gamma delta 1 CAR T therapies."

Third Quarter 2025 and Recent Operational Highlights:

Autoimmune diseases

Announced positive preliminary data in LN and SLE patients from Phase 1 study of ADI-001 in autoimmune diseases. In October 2025, Adicet announced positive initial safety and efficacy data from seven patients (five LN and two SLE patients) dosed with ADI-001 in the ongoing Phase 1 trial, with follow-up ranging from two to nine months as of the August 31, 2025 data cut-off date. All patients demonstrated rapid and sustained reductions in the SLEDAI-2K score and PGA. All patients in the LN cohort achieved improved renal function, including three complete renal responses and Definition of Remission In Systemic lupus erythematosus (DORIS) remissions, and two partial responses. ADI-001 also demonstrated multiple hallmarks of immune reset with subsequent emergence of naïve and previously undetected B cell repertoire following single dose treatment. ADI-001 was generally well tolerated and demonstrated a favorable safety profile, with no Grade 2 or higher Cytokine Release Syndrome (CRS), and no cases of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) observed.
Based on these results, the Company plans to request a meeting with the FDA in the first quarter of 2026 to inform potential Phase 2 pivotal trial design, with the initiation of the study in LN or LN and SLE patients anticipated to commence in the second quarter of 2026.

Enrollment ongoing in ADI-001 Phase 1 program. Adicet is actively enrolling patients in its Phase 1 clinical trial evaluating ADI-001 in autoimmune diseases which include: LN, SLE, SSc, IIM, SPS and AAV. Adicet expects to provide an LN and SLE clinical update as well as an SSc clinical update in the first half of 2026.
Actively enrolling patients with treatment-refractory RA in Phase 1 study of ADI-001 evaluating potential to reduce the need for conditioning. The Company is enrolling patients with treatment-refractory RA in a Phase 1 study of ADI-001 evaluating two lymphodepletion regimens: cyclophosphamide alone and cyclophosphamide with fludarabine. Adicet expects to provide a clinical update on the Phase 1 trial in the second half of 2026.
Solid tumor indications

Presented ADI-212 preclinical data at the 32nd annual Prostate Cancer Foundation Scientific Retreat. Adicet is continuing to advance preclinical development of ADI-212, an optimized next-generation gene-edited and armored clinical candidate designed to target PSMA. ADI-212 is engineered to express a novel CAR binder designed to support enhanced tolerability and tumor-specific recognition. It integrates membrane-tethered IL-12 (mbIL-12) armoring and CRISPR/Cas9 mediated disruption of subunit 12 of the mediator complex (MED12) to enhance potency in solid tumors and deliver multiple anti-tumor mechanisms of action within the tumor microenvironment. In October, Adicet presented preclinical data at the 32nd Annual Prostate Cancer Foundation Scientific Retreat supporting these design elements and functional enhancements in multiple models of disease.
Regulatory filing on track for ADI-212 in mCRPC. Adicet plans to submit a regulatory filing for ADI-212 for the treatment of mCRPC in the first quarter of 2026. The Company expects to share initial clinical data from the ADI-212 program in the second half of 2026, subject to regulatory clearance to proceed with a clinical trial.
Corporate updates

Raised $74.8 million in net proceeds in registered direct offering. In October 2025, Adicet successfully raised $74.8 million in net proceeds through an underwritten registered direct offering of equity securities, extending its cash runway into the second half of 2027.
Financial Results for Third Quarter 2025:

Research and Development (R&D) Expenses: R&D expenses were $22.9 million for the three months ended September 30, 2025, compared to $26.3 million during the same period in 2024. The decrease in R&D expenses was due to a $1.8 million decrease in payroll and personnel expenses, and a $1.0 million decrease in lab supplies and materials related to lower headcount, a $0.7 million decrease in expenses related to contract development and manufacturing organizations (CDMOs) and contracted R&D services due to lower utilization at external CDMOs, a $0.7 million decrease in expenses related to R&D consultants, partially offset by a $0.8 million of expenses related to contract research organizations; and a $0.1 million decrease in facility-related expenses.
General and Administrative (G&A) Expenses: G&A expenses were $5.1 million for the three months ended September 30, 2025, compared to $6.9 million during the same period in 2024. The decrease in G&A expenses was primarily due to a $1.6 million decrease in payroll and personnel expenses primarily related to a decrease in stock-based compensation expense, and a $0.1 million decrease in facility-related expenses.
Net Loss: Net loss for the three months ended September 30, 2025 was $26.9 million, or a net loss of $0.29 per basic and diluted share, including non-cash stock-based compensation expense of $2.5 million, as compared to a net loss of $30.5 million, or a net loss of $0.34 per basic and diluted share, including non-cash stock-based compensation expense of $6.8 million during the same period in 2024.
Cash Position: Cash, cash equivalents and short-term investments were $103.1 million as of September 30, 2025, compared to $176.3 million as of December 31, 2024. Subsequent to September 30, the Company received approximately $74.8 million of net proceeds from a registered direct offering. The Company expects that its cash and cash equivalents and short-term investments as of September 30, 2025, together with the proceeds raised after quarter end, will be sufficient to fund its operating expenses into the second half of 2027.

(Press release, Adicet Bio, NOV 5, 2025, View Source [SID1234659494])

Tempus Announces Six Abstracts Accepted for Presentation at the Society for Immunotherapy of Cancer Annual Meeting 2025

On November 5, 2025 Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine, reported that six abstracts have been accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2025. The meeting is taking place November 5 – 9 at the Gaylord National Convention Center in National Harbor, Maryland.

"We’re excited to join the oncology community at this year’s meeting and highlight our latest research and progress in advancing the immuno-oncology field," said Ezra Cohen, MD, Chief Medical Officer of Oncology at Tempus. "Our latest findings demonstrate the potential of integrated, data-driven approaches to refine biomarkers, improve prediction of immunotherapy response, and inform the development of next-generation tools for patient stratification."

This year, Tempus will highlight its latest scientific and clinical research findings via six poster presentations.

A novel multi-omic algorithm to predict real-world outcomes among patients with rare, advanced, solid cancers treated with off-label immune checkpoint inhibitors
Date/Time: Friday, November 7, 5:10–6:35 p.m. ET
Location: Exhibit Halls AB
Presentation Number: 157
Summary: This study investigates the utility of the Immune Profile Score (IPS) as a molecular signature to predict the effectiveness of immune checkpoint inhibitor (ICI) therapy in rare, advanced solid cancers. Given the clinical unmet need for rare, heterogeneous cancers, the study evaluated 90 eligible patients from Tempus’ de-identified real-world database who had a rare, advanced solid cancer diagnosis and received off-label ICI treatment, excluding those with high TMB or MSI. Patients were further categorized as IPS-high or IPS-low. The findings demonstrated that IPS-high patients experienced significantly longer overall survival compared to those categorized as IPS-low. Importantly, IPS maintained its prognostic significance across all patient subgroups and clinically relevant confounders. These results support IPS as a pan-cancer biomarker capable of accurately stratifying ICI treatment outcomes and potentially supporting the label expansion of ICIs to various rare cancer types.
MAIT cell abundance within tumors are associated with key clinical characteristics across solid tumors
Date/Time: Friday, November 7, 5:10–6:35 p.m. ET
Location: Exhibit Halls AB
Presentation Number: 133
Summary: An analysis of 190,189 patients, utilizing T-cell receptor (TCR) sequencing data from Tempus’ de-identified real-world database, investigated the prevalence and distribution of mucosal-associated invariant T (MAIT) cells across numerous solid tumor types. The study determined MAIT cell abundance using TCRα chains, with comparisons adjusting for overall T cell infiltration or total TCR’s detected where relevant. MAIT cell abundance was highest in tumors of mucosal origin, such as colorectal and gastroesophageal cancers, and higher MAIT cell levels were statistically significantly in younger patients, males, and non-smokers. Furthermore, the prevalence of MAIT cells showed associations with important clinical and molecular factors, including reduced MAIT cell abundance in PD-L1 high (TPS ≥50%; pan-cancer), microsatellite instability (MSI)-high (pan-cancer and colorectal cancer), and microbial factors such as lower bacterial load (pan-cancer). These findings suggest that MAIT cell prevalence may have important clinical implications and may serve as a promising biomarker and immunotherapy target.
TargetR: Automated multi-omics report framework for target characterization and validation of immunotherapy and targeted therapy candidates across cancers
Date/Time: Friday, November 7; 5:10–6:35 p.m. ET
Location: Exhibit Halls AB
Presentation Number: 1115
Summary: A detailed computational framework, TargetR, was developed by integrating public and real-world multi-omics datasets to accelerate the discovery and validation of immunotherapy targets. This approach unified pharmacologic, genomic, transcriptomic, and proteomic data, utilizing advanced analytics to assess target potential based on criteria such as normal tissue expression, mutational load, and copy number variation (CNV) correlation with expression. Validation of findings can then be performed using Tempus’ de-identified real-world database, which provides clinical features and outcome data. The framework generated an automated, user-friendly report with actionable insights, enabling the identification and prioritization of targets for treatments like bispecific T-cell engagers and CAR-T therapies, thereby supporting the development of next-generation immunotherapies.
A multi-omic immune profile score (IPS) stratifies real-world outcomes of microsatellite stable (MSS) advanced colorectal cancer patients treated with immune checkpoint inhibitors
Date/Time: Saturday, November 8; 5:10–6:35 p.m. ET
Location: Exhibit Halls AB
Presentation Number: 134
Summary: This exploratory study investigated the potential of Tempus’ Immune Profile Score (IPS), a DNA- and RNA-based molecular signature, to act as a predictive biomarker for immune checkpoint inhibitor (ICI) benefit in patients with microsatellite stable (MSS) advanced colorectal cancer (CRC). Tempus’ de-identified real-world database was utilized to identify 46 eligible MSS CRC patients who received an ICI alone or ICI-containing regimen in the third line (3L) or beyond. Using pre-ICI tissue, patients were stratified into IPS-High versus IPS-Low groups. The results demonstrated a clinically meaningful improvement in real-world overall survival (rwOS) for the IPS-High group compared to the IPS-Low group. Furthermore, a comparison of IPS risk stratification on ICI therapy versus prior non-ICI regimen provided additional insight about IPS’s utility as an ICI-specific biomarker. This hypothesis-generating data address an unmet need for patients whom an ICI therapy and predictive biomarker are urgently needed.
Ultrahigh tumor mutational burden (TMB) is associated with improved survival outcomes in patients (Pts) treated with immune checkpoint inhibitors (ICIs)
Date/Time: Saturday, November 8, 2025; 5:10–6:35 p.m. ET
Location: Exhibit Halls AB
Presentation Number: 136
Summary: This research evaluates the prognostic value of defining an "ultrahigh" tumor mutational burden (TMB) threshold (≥40 mutations/MB) compared to the standard 10 mt/MB cutoff for patients receiving immune checkpoint inhibitor (ICI) therapy. Using Tempus Lens, the research team defined a cohort of 17,449 patients with five different cancer types (melanoma, lung, GI, non-melanoma skin, and uterine) from Tempus’ de-identified multimodal database. The analysis sought to compare real-world objective response rates (rwORR) and overall survival (rwOS) across low, high, and ultrahigh TMB groups. The findings indicate that patients in the ultrahigh TMB group experience significantly improved clinical outcomes, including enhanced rwORR and better rwOS. This ultrahigh TMB status is also linked to a distinct tumor microenvironment, specifically showing a higher degree of regulatory T cell and myeloid cell infiltration, suggesting that ultrahigh TMB may serve as a novel marker for predicting ICI responsiveness.
Impact of androgen receptor mutations on immune infiltration in castration resistant prostate cancer
Date/Time: Saturday, November 8; 5:10–6:35 p.m. ET
Location: Exhibit Halls AB
Presentation Number: 140
Summary: A detailed analysis using Tempus’ de-identified real-world database examined the relationship between androgen receptor (AR) alterations and the immune microenvironment in 1,556 patients with castration-resistant prostate cancer (CRPC). The study specifically investigated AR mutations, amplifications, and ARv7 splicing detected via DNA (Tempus xT) and RNA (Tempus xR) sequencing. Over half of the CRPC patients exhibited these AR alterations, which were associated with significantly decreased immune infiltration and reduced expression of key immunotherapy targets like PD−1, PD−L1, and CTLA−4. Regression analysis confirmed this link to decreased immune infiltration was independent of tumor mutational burden (TMB) and tumor purity. These findings suggest that AR mutations contribute to a reduced immune response, potentially serving as a mechanism of resistance to treatment, and underscore the necessity of using AR status to stratify CRPC patients for immunotherapy.

(Press release, Tempus, NOV 5, 2025, View Source [SID1234659493])