On May 13, 2025 Orchard Therapeutics, a Kyowa Kirin company, reported a publication on long-term safety and efficacy outcomes for Lenmeldy (atidarsagene autotemcel) in the treatment of early-onset metachromatic leukodystrophy (MLD) (Press release, Orchard Theraputics, MAY 13, 2025, View Source [SID1234653172]). The manuscript, titled, "Long-term effects of atidarsagene autotemcel for metachromatic leukodystrophy" (F. Fumagalli, V. Calbi, A. Aiuti, et. al.) was published in the April 24 issue of NEJM.

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MLD is an ultra-rare, rapidly progressive, irreversible and ultimately fatal neurometabolic disease that affects approximately one in 100,000 live births. It is caused by an error in the gene responsible for encoding the enzyme arylsulfatase A (ARSA) leading to neurological damage and developmental regression. In the most severe form of MLD, babies develop normally but in late infancy start to rapidly lose the ability to walk, talk and interact with the world around them. These children eventually deteriorate into a vegetative state, which may require 24-hour intensive care, and the majority pass away within five years of symptom onset, creating an enormous emotional and financial burden on the family. Lenmeldy is the only approved therapy intended to correct the underlying cause of MLD for eligible patients in the United States (U.S.). It is known as Libmeldy in Europe.

The FDA approval of Lenmeldy is based on data from pediatric patients with early-onset MLD enrolled in two single-arm, open-label clinical studies or treated under European expanded access frameworks, who received a one-time administration of the hematopoietic stem cell (HSC) gene therapy and compared with natural history data from untreated patients. The NEJM publication details clinical outcomes of children treated in these studies. All treated patients were administered HSC gene therapy and subsequently monitored at Ospedale San Raffaele in Milan, Italy. The primary endpoint was severe motor impairment-free survival (sMFS), defined as the interval from birth to the first occurrence of loss of locomotion and loss of sitting without support (Gross Motor Function Classification-MLD [GMFC-MLD] Level ≥ 5) or death.

With more than 12 years of follow-up in the earliest treated patients (median 6.76 years) and more than 250 patient years, treatment with Lenmeldy significantly extended overall survival and resulted in the preservation of motor function and cognitive skills in most late infantile MLD patients past ages at which untreated patients showed severe cognitive and motor impairments. Lenmeldy also resulted in the preservation of motor function and cognitive skills in some early juvenile MLD patients which is not expected when compared to untreated patients.

Treatment with Lenmeldy was well-tolerated, with no treatment-related serious adverse events. Most adverse events were associated with busulfan conditioning or background disease. The most common non-laboratory adverse reactions (incidence ≥ 10%) were: febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device related infections (31%), other viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%). The most common laboratory abnormalities were: elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes (23%). Please see below for additional details and Important Safety Information.

"Lenmeldy represents a significant step forward in the treatment of MLD, a cruel and ultimately fatal disease for which there were previously no approved treatment options beyond supportive and end-of-life care," said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard Therapeutics. "These compelling results, which encompass more than a cumulative 250 years of patient experience, continue to demonstrate the ability of Lenmeldy to preserve motor and cognitive function in eligible children with MLD particularly when treatment is administered prior to the onset of symptoms."

Dr. Gaspar continued, "These long-term results, coupled with the homogenous, predictable and precipitous decline and eventual death observed in the natural history cohort, underscores the urgent need to enable timely and accurate diagnosis and intervention through the proliferation of universal newborn screening for MLD."

Summary of Participation at ASGCT (Free ASGCT Whitepaper) 2025

The company also announced six presentations (three oral and three posters) will be featured at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 28th Annual Meeting taking place May 13-17 in New Orleans.

Featured data include several accepted abstracts and presentations detailing clinical, biochemical and other functional outcomes from across the company’s commercial- and clinical-stage neurometabolic portfolio in metachromatic leukodystrophy (MLD), the Hurler subtype of mucopolysaccharidosis type I (MPS-IH), and mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome type A.

Company researchers will also present data derived from its efforts to develop an automated manufacturing process for HSC gene therapy production and in developing an HSC gene therapy approach for the treatment of another lysosomal storage disorder.

Finally, Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics, will give an invited talk on Friday, May 16 at 8:00 a.m. CDT, titled "Developing and delivering hematopoietic stem cell gene therapies to patients with rare neurometabolic diseases," which will explore key insights into the development and delivery of one-time treatments for rare neurometabolic diseases and beyond.

Details of the oral presentations are as follows (all times in CDT):

Title: Lentiviral hematopoietic stem cell gene therapy (atidarsagene autotemcel) for late juvenile metachromatic leukodystrophy (MLD): Interim analysis of a Phase III trial
Date/Time: Wednesday, May 14 at 2:45 p.m.
Presenter: Valeria Calbi
Title: Treatment effect of atidarsagene autotemcel (arsa-cel) in age-matched treated vs. untreated sibling pairs with early-onset metachromatic leukodystrophy (MLD)
Date/Time: Friday, May 16 at 1:30 p.m.
Presenter: Valeria Calbi
Title: Extensive detoxification and favorable effects on systemic clinical outcomes after Hematopoietic Stem Cell Gene Therapy for Mucopolysaccharidosis Type I-Hurler (OTL-203)
Date/Time: Friday, May 16 at 2:00 p.m.
Presenter: Giulia Consiglieri
Details of the poster presentations are as follows (all times in CDT):

Title: Toward the development of an automated manufacturing process for hematopoietic stem cell gene therapies
Date/Time: Wednesday, May 14 from 5:30 to 7:00 p.m.
Presenter: Vasileios Paraskevas
#1302
Title: Anti-SGSH antibodies following hematopoietic stem cell (HSC) gene therapy in MPSIIIA patients neither impact engraftment of genetically modified HSC nor interfere with multi-compartment substrate reduction
Date/Time: Thursday, May 15 from 5:30 to 7:00 p.m.
Presenter: Brian Bigger
#1513
Title: Correction of Glycogen Accumulation in Muscle, Heart and CNS in a Pre-Clinical Model of Hematopoietic Stem Cell Gene Therapy for Pompe Disease
Date/Time: Thursday, May 15 from 5:30 to 7:00 p.m.
Presenter: Piv Sagoo
#1514
About MLD
MLD is a rare and life-threatening inherited disease of the body’s metabolic system estimated to occur in approximately one in every 100,000 live births based on existing literature. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity, and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50 percent and 44 percent at 10 years for juvenile patients.i

About Lenmeldy / Libmeldy
Lenmeldy (atidarsagene autotemcel), formerly known as OTL-200, is the only approved therapy in the U.S. for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early-symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD).

For additional details about Lenmeldy, please refer to the full Prescribing Information.

In Europe, Lenmeldy is known as Libmeldy, where it has been approved by the European Commission (EC) and UK Medicines and Healthcare products Regulatory Agency (MHRA). For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website.

The program was originated by and developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.

INDICATION

LENMELDY (atidarsagene autotemcel) is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ), or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Thrombosis and Thromboembolic Events:

Treatment with LENMELDY may increase the risk of thrombosis and thromboembolic events. A child with PSEJ MLD died after experiencing a left hemisphere cerebral infarction secondary to a thrombotic event in a large blood vessel approximately 1 year after treatment with LENMELDY. Evaluate the risk factors for thrombosis prior to and after LENMELDY infusion according to best clinical practice.

Encephalitis:
Treatment with LENMELDY may increase the risk of encephalitis. A child with ESEJ developed a serious event of encephalitis after treatment with LENMELDY. The etiology of this event is unclear but attribution to LENMELDY cannot be ruled out. Treatment with LENMELDY may trigger a relapsing-remitting pattern of disease progression. No other events related to encephalitis have been reported during the clinical development of LENMELDY. Monitor children for signs or symptoms of encephalitis after LENMELDY treatment.

Serious Infection:
In the period between start of conditioning and within 1 year after LENMELDY treatment, severe Grade 3 infections occurred in 39% of all children (21% bacterial, 5% viral, 5% bacterial and viral or bacterial and fungal, and 8% unspecified). Grade 3 febrile neutropenia developed within 1 month after LENMELDY infusion in 82% of children. In the event of febrile neutropenia, monitor for signs and symptoms of infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated. Monitor children for signs and symptoms of infection after myeloablative conditioning and LENMELDY infusion and treat appropriately. Administer prophylactic antimicrobials according to best clinical practice.

Veno-Occlusive Disease:

Three children (8%) treated in clinical trials of LENMELDY developed veno-occlusive disease (VOD) with one Grade 4 SAE and two Grade 3 AEs. None of these three events met Hy’s Law criteria. Monitor children for signs and symptoms of VOD including liver function tests in all children during the first month after LENMELDY infusion. Consider prophylaxis for VOD with anti-thrombotic agents based on risk factors for VOD and best clinical practice.

Delayed Platelet Engraftment (DPE):
DPE has been observed with LENMELDY treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in children with prolonged thrombocytopenia. In clinical trials of LENMELDY, 4 (10%) children had delayed platelet engraftment after day 60 (range day 67-109), with 3 children requiring platelet transfusions until engraftment occurred. Patients should be informed of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding until platelet engraftment and recovery are achieved.

Neutrophil Engraftment Failure:
There is a potential risk of neutrophil engraftment failure after treatment with LENMELDY. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a child treated with LENMELDY, provide rescue treatment with the unmanipulated back-up collection of CD34+ cells.

Insertional Oncogenesis:
There is a potential risk of LVV-mediated insertional oncogenesis after treatment with LENMELDY. Children treated with LENMELDY may develop hematologic malignancies and should be monitored life-long. Monitor for hematologic malignancies with a complete blood count (with differential) annually and integration site analysis as warranted for at least 15 years after treatment with LENMELDY. In the event that a malignancy occurs, contact Orchard Therapeutics at 1-888-878-0185 for reporting and to obtain instructions on collection of samples for testing.

Hypersensitivity Reactions:
The dimethyl sulfoxide (DMSO) in LENMELDY may cause hypersensitivity reactions, including anaphylaxis which is potentially life-threatening and requires immediate intervention. Hypersensitivity including anaphylaxis can occur in children with and without prior exposure to DSMO. Monitor for hypersensitivity reactions during infusion and after infusion.

Anti-Retroviral Use:
Children should not take prophylactic HIV anti-retroviral medications for at least one month prior to mobilization, or for the expected duration of time needed for the elimination of the medications. Anti-retroviral medications may interfere with the manufacturing of LENMELDY. If a child requires antiretrovirals for HIV prophylaxis, initiation of LENMELDY treatment should be delayed until confirmation of a negative test for HIV.

Interference With Serology Testing:
Due to the likelihood of a false-positive test for HIV, children who have received LENMELDY should not be screened for HIV infection using a PCR-based assay.

USE IN SPECIFIC POPULATIONS

Females and Males of Reproductive Potential

Pregnancy Testing
As a precautionary measure, a negative serum pregnancy test must be confirmed prior to the start of mobilization, and reconfirmed prior to conditioning procedures, and before administration of LENMELDY in females of childbearing potential.

Contraception

Consult the Prescribing Information of the mobilization and conditioning agents for information on the need for effective contraception. Males capable of fathering a child and females of childbearing age should use an effective method of contraception from start of mobilization through at least 6 months after administration of LENMELDY.

Infertility
There are no data on the effects of LENMELDY on fertility.

Data are available on the risk of infertility with myeloablative conditioning. In clinical trials of LENMELDY, seven children (50% of females) developed ovarian failure. Advise children of the option to cryopreserve semen or ova before treatment, if appropriate.

For additional safety information, please see the full Prescribing Information.

On May 13, 2025 Stylus Medicine, Inc. ("Stylus"), a biotechnology company dedicated to developing transformative in vivo genetic medicines, reported presentations showcasing its genome engineering approach and in vivo CAR-T platform at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 28th Annual Meeting being held May 13-17, 2025 in New Orleans, Louisiana (Press release, Stylus Medicine, MAY 13, 2025, View Source(asgct)-28th-annual-meeting-1 [SID1234653001]).

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"On the heels of our company launch and Series A financing, the Stylus team is honored to present our work to the scientific community at this year’s ASGCT (Free ASGCT Whitepaper) Annual Meeting, highlighting our advances in recombinase engineering and demonstrating the therapeutic potential of our targeted LNP/recombinase-based in vivo CAR-Ts," said Jason Fontenot, Ph.D., Chief Scientific Officer of Stylus Medicine. "At Stylus, we are committed to realizing the revolutionary potential of genetic medicines. We are taking a focused "medicines first" approach to build a potent, flexible, and scalable in vivo platform, with the goal of bringing the curative promise of CAR-T therapies to all patients in need."

ASGCT Annual Meeting Presentation Details:

Oral Presentation:

Title: Engineering High-Efficiency, High-Specificity Recombinases for Therapeutic In Vivo Genome Engineering

Session: Novel Approaches to Gene Targeting and Gene Correction

Presenter: Christopher J. Wilson, Ph.D., Senior Vice President, Genome Engineering

Date, Time and Location: Thursday, May 15, 2025, 1:30 PM – 3:15 PM CT, New Orleans Theater B

Abstract: 188

Summary: Stylus will present the development of therapeutic-grade recombinases for in vivo genetic medicines. The company reports engineering high-efficiency, high-specificity recombinases targeted to a novel safe harbor site in the human genome. The company’s engineered recombinases act without the use of landing pads, protein fusions, or guide RNAs and possess a well-defined integration profile. These proprietary recombinases serve as the foundation of Stylus’ powerful and elegant off-the-shelf, in vivo genetic medicines platform, which features single-step insertion of multi-kb therapeutic payloads.

Poster Presentation:

Title: Efficient and Effective In Vivo CAR-T Generation Using Recombinase-Based, Precise, High-Capacity, Off-the-Shelf, LNP-Based In Vivo Genomic Engineering

Presenter: Celeste Richardson, Ph.D., Senior Vice President, Immunology

Date and Time: Tuesday, May 13, 2025, 6:00 PM – 7:30 PM CT

Abstract: 797

Summary: Stylus will present advances from its powerful and elegant in vivo CAR-T platform, which combines a proprietary recombinase that enables sequence-specific genome integration with cell-targeted lipid nanoparticle (LNP) delivery. Using a humanized NSG mouse tumor model, a single dose of the company’s off-the-shelf in vivo CAR-T therapy demonstrated rapid and sustained tumor regression. By combining engineered recombinases with targeted LNP delivery, Stylus has created a platform to enable flexible and scalable in vivo CAR-T therapies, overcoming major limitations of ex vivo cell therapy.

On May 13, 2025 Stylus Medicine, Inc. ("Stylus"), a biotechnology company dedicated to developing transformative in vivo genetic medicines, reported to have emerged from stealth with $85 million in financing (Press release, Stylus Medicine, MAY 13, 2025, View Source [SID1234653000]). Stylus’ funding includes a $45 million Series A extension financing with participation from RA Capital Management, Khosla Ventures, and six new investors including Chugai Venture Fund, Eli Lilly and Company, and Johnson & Johnson Innovation – JJDC. This financing follows a $40 million Series A investment from founding investors RA Capital and Khosla Ventures.

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Stylus will use this financing to advance its in vivo genetic medicines platform and pipeline of in vivo therapeutic programs. The company’s powerful and elegant engineering platform combines sequence-specific genome integration with cell-targeted lipid nanoparticle (LNP) delivery. The platform is based on Stylus-designed therapeutic-grade recombinases capable of encoding polyfunctional multi-kb payloads with high efficiency, high specificity, and high fidelity. This system enables durable, flexible, and scalable in vivo cell engineering, overcoming major limitations of ex vivo cell therapy manufacturing and expanding the reach of transformative genetic medicines.

"Stylus was established to reimagine how genetic medicines reach patients. At the core of our approach are three defining features of an ideal therapy: safe and targeted in vivo delivery, specific integration, and durable expression of a therapeutic payload," said Emile Nuwaysir, Ph.D., Chairman and Chief Executive Officer of Stylus. "By removing the complexity of ex vivo and viral manufacturing, we will dramatically simplify patient treatment. Our goal is to bring the life-saving promise of genetic medicines to every patient in need, starting with CAR-T therapies."

"Stylus was created in 2022 by Raven, RA Capital’s healthcare incubator, and Khosla Ventures to solve the fundamental challenges holding back genetic medicines," said Joshua Resnick, M.D., Partner at RA Capital and President of Raven. "The Stylus system is incredibly elegant, and Stylus has the right team, capital, and strategy to succeed. The company has the potential to vastly expand the availability of life-changing therapies, while creating a scalable, efficient model that is attractive from both a clinical and commercial perspective."

Leadership and Organization

The Company’s leadership includes Emile Nuwaysir, Ph.D., Chairman and Chief Executive Officer, and Jason Fontenot, Ph.D., Chief Scientific Officer.

Dr. Nuwaysir brings more than 25 years of experience in executive leadership positions in the cell and gene therapy field to the role. As a serial entrepreneur and operator, he has launched and led multiple biotechnology companies from inception to exit, including senior leadership roles at BlueRock Therapeutics (acquired by Bayer), Cellular Dynamics (acquired by FujiFilm), and NimbleGen (acquired by Roche). He was most recently the CEO of Ensoma and the CEO and Chairman of BlueRock Therapeutics. Dr. Nuwaysir is also the past Chairman of the Alliance for Regenerative Medicine.

Dr. Fontenot, Stylus’ Chief Scientific Officer (CSO), brings more than two decades of experience in senior scientific roles and a track-record of leadership in cell and gene therapy. He was most recently the CSO of Sangamo Therapeutics and the CSO of Immusoft Corporation. He led the Exploratory Research group at Juno Therapeutics and was a group leader in Immunology Research at Biogen. Dr. Fontenot’s academic research was focused on lineage specification in the immune cells. His seminal discoveries in regulatory T cell biology established the molecular basis for dominant immune tolerance with broad implications in autoimmunity and oncology.

"The genetic medicines revolution began decades ago, but despite the immense therapeutic potential we’ve treated a limited number of patients because of manufacturing and delivery challenges, and the inability to deliver large genetic payloads. Most genetic medicines available today are an important proof-of-concept, but not a practical solution," said Nessan Bermingham, Ph.D., Operating Partner at Khosla Ventures. "Stylus set out with a bold vision to solve those challenges. Achieving this vision requires exceptional leadership, and with Emile and Jason at the helm, Stylus is optimally positioned to realize our goal to bring transformative genetic medicines to the millions of patients who desperately need them."

Drs. Nuwaysir and Fontenot are part of an accomplished leadership team, and an experienced Board of Directors comprised of industry veterans and scientific innovators, including:

Board of Directors

Emile Nuwaysir, Ph.D., Chairman and Chief Executive Officer
Nessan Bermingham, Ph.D., Operating Partner at Khosla Ventures, formerly Chief Executive Officer at Intellia Therapeutics
John Gustofson, President at Chugai Venture Fund, formerly Managing Director at AbbVie Ventures
Patrick Hsu, Ph.D., Scientific Founder of Stylus Medicine, Co-Founder of the Arc Institute, and Assistant Professor of Bioengineering and Deb Faculty Fellow at the University of California, Berkeley
Joshua Resnick, M.D., Partner at RA Capital Management and President of Raven, RA Capital’s healthcare incubator
Scientific Founders

Patrick Hsu, Ph.D., Co-Founder of the Arc Institute and Assistant Professor of Bioengineering and Deb Faculty Fellow at the University of California, Berkeley
Ami S. Bhatt, M.D., Ph.D., Professor of Medicine & Genetics at Stanford University
Michael C. Bassik, Ph.D., Associate Professor of Genetics at Stanford University
Lacramioara Bintu, Ph.D., Assistant Professor of Bioengineering at Stanford University
"Recombinases are ideal enzymes for integrating large genetic payloads into the genome. Stylus’ unique approach centers on an extensive, proprietary library of therapeutic-grade recombinases, optimized through computational design and machine learning for protein engineering," said Patrick Hsu, Ph.D. "By developing engineered recombinases for in vivo genetic medicines, Stylus is unlocking a new era of therapeutic possibilities."

On May 13, 2025 Invenra Inc., a pioneer in multispecific antibody discovery and development, announces the launch of its T-Body trispecific antibody platform, a next-generation technology designed to reliably direct correct chain pairing and afford high expression and assembly efficiency in a variety of antibody constructs, including complex trispecific constructs (Press release, Invenra, MAY 13, 2025, View Source [SID1234652999]). Building on the success of Invenra’s B-Body bispecific platform, the T-Body platform expands the company’s capabilities to address complex therapeutic targets with enhanced developability.

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"Trispecific antibodies represent a major leap forward in therapeutic design, and our T-Body platform offers a unique approach to unlock their potential," said Roland Green, Ph.D., CEO and Chairman of Invenra. "By integrating proprietary CH3 domains, streamlining purification, and achieving strong expression yields, we’re empowering partners to rapidly discover and advance a new class of multispecific therapeutics."

Designed for Versatility and Manufacturability

The T-Body platform features an IgG-like architecture with proprietary CH3 domain pairs that substitute for traditional CH1/CL domains in two Fab arms. This configuration improves chain pairing, reduces mispairing, and supports efficient expression and assembly in mammalian cells. The design also enables "Plug & Play" variable domain compatibility, allowing insertion of VH/VL pairs from diverse sources—including phage libraries, humanized mice, and AI-designed antibodies.

Invenra’s T-Body platform features include:

Proprietary CH3 Design: Improves heavy/light chain pairing and overall assembly.
Streamlined Purification: One-step purification with Protein A and anti-CH1 resin compatibility.
Robust Expression: High yields in multiple transient expression systems.
Flexible Targeting: Supports multivalent and/or multispecific formats with both kappa and lambda light chains.
Manufacturing-Ready: Compatible with standard IgG production processes for rapid scale-up.
Expanding the Future of Multispecific Antibodies

With the T-Body platform, Invenra continues its mission to accelerate next-generation multispecific antibody discovery in areas such as oncology, autoimmune disease, and immunotherapy. The platform’s modularity and developability profile position it for internal programs and strategic partnerships aimed at addressing complex biology through engineered multispecific formats.

"This platform is a natural extension of our antibody engineering leadership," Green added. "We’re excited to work with partners to move trispecific candidates from concept to clinic."

Invenra is highlighting the T-Body platform at the 21st Annual PEGS Boston May 12-16, with details available at its poster (A051), booth (612), and online at invenra.com.

On May 13, 2025 Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine and patient care, reported the presentation of six posters, including one oral presentation, at the 2025 annual meeting of the Professional Society for Health Economics and Outcomes Research (ISPOR), taking place May 13-16 in Montreal, Canada (Press release, Tempus, MAY 13, 2025, View Source [SID1234652998]). Tempus researchers are showcasing scientific and clinical studies highlighting the impact of AI and real-world data on health economics and outcomes research.

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"The research we’re presenting at ISPOR 2025 underscores the powerful potential of integrating clinical, molecular, and claims data to unlock actionable insights that drive more personalized and effective cancer care," said Emilie Scherrer, Senior Director and Head of Outcomes Research, at Tempus. "At Tempus, we share ISPOR’s deep focus on empowering providers and health systems with the real-world data they need to optimize treatment strategies and improve outcomes for their patients."

Research highlights include:

Oral Presentation: Oncology Trial Emulation Using Real-World Electronic Health Record Data: Results of the Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation (CARE) Initiative
Date/Time: Thursday, May 15; 10:15 AM – 11:15 AM ET

Overview: The Coalition to Advance Real-World Evidence through Randomized Controlled Trial (RCT) Emulation (CARE) Initiative seeks to advance understanding of when real-world data (RWD) can generate valid treatment effectiveness estimates by emulating RCTs. This study presents findings from three oncology emulations. The KEYNOTE-189 (metastatic NSCLC) and PALOMA-2 (advanced breast cancer) trials were emulated using electronic health record datasets. Trial entry criteria were applied, and treatment status was based on first-line medications. Inverse probability of treatment weighting controlled for baseline confounding, and Kaplan-Meier and Cox models estimated primary outcomes. In the KEYNOTE-189 emulation, the real-world progression-free survival (rwPFS) hazard ratio (HR) in one dataset was similar to the RCT finding, while the other was closer to the null. PALOMA-2’s rwPFS HR was also closer to the null. Real-world overall survival estimates in KEYNOTE-189 also varied across datasets. The researchers conclude that RWD oncology emulation conclusions depend on dataset features, route of administration, and real-world follow-up characteristics.
Poster Presentation: Impact of Adverse Event Definitions on Real-World Detection of Immune-Related Adverse Events
Date/Time: Thursday, May 15; 10:30 AM – 1:30 PM ET

Location: Exhibit Hall 220B-E, Poster #6044
Overview: Researchers investigated the impact of varying definitions on the identification of immune-related adverse events (irAEs) in real-world data (RWD) from non-small cell lung cancer (NSCLC) patients treated with immune checkpoint blockade (ICB). The research utilized Tempus clinico-genomic data linked to Komodo Health’s claims to analyze irAEs within one year of ICB treatment in patients with stage 3C+ NSCLC. Three peer-reviewed irAE definitions—differing in included irAEs, ICD-10 codes, and pre-treatment washout periods—were applied to the cohort of 4,831 patients. The overall prevalence of irAEs varied significantly across definitions: 41.0% (n=1,981) for Study A (9 irAEs), 75.4% (n=3,849) for Study B (10 irAEs), and 5.4% (n=264) for Study C (3 irAEs). This study demonstrates that irAE identification in RWD varies based on the definitions used, which can affect post-market surveillance, clinical practice guidelines, and patient care. The authors emphasize the need for researchers to accurately communicate the definitions used and conduct sensitivity analyses.
Poster Presentation: Comparison of Demographics and Clinical Characteristics using Real World Data from Tempus Multimodal Database and SEER Cancer Registry Across 17 Solid Cancer Cohorts
Date/Time: Thursday, May 15; 4:00 PM – 7:00 PM ET
Location: Exhibit Hall 220B-E, Poster #6019

Overview: This study benchmarked the Tempus multimodal database — a real-world data source with clinical and biomarker data from cancer patients — against the SEER cancer registry. Analyzing data from 63,520 patients with solid tumors diagnosed between 2016 and 2021, researchers compared baseline demographic, clinical, and treatment characteristics against the SEER database. The proportion of cancer types of new cancer cases were similar among the two databases. The Tempus database showed a larger representation of patients from the Midwest, whereas the SEER database had a heavy representation from the West. Tempus patients were younger on average but had more advanced cancer staging. Additionally, the Tempus database had more racial diversity based on self-reported race and more complete treatment data. In conclusion, the Tempus and SEER databases show general comparability in demographics and clinical characteristics, but the Tempus database provides greater treatment data granularity and captures more late-stage disease, attributable to sequencing patterns in clinical care.
Poster Presentation: Assessing the Completeness of Oncology Treatment Data from Administrative Claims: A Benchmarking Study Against Abstracted EHRs Using Patient-Level Linkages
Date/Time: Thursday, May 15; 4:00 PM – 7:00 PM ET
Location: Exhibit Hall 220B-E, Poster #6041

Overview: This study benchmarked oncology treatment data from administrative claims against abstracted electronic health records (EHR) for 6,487 stage 4 lung adenocarcinoma patients diagnosed between 2020 and 2023. Claims data (open and closed) were linked using de-identified patient tokens, with EHR data considered the ground truth. Sensitivities and positive predictive values (PPVs) were calculated for 13 infusional and 3 oral medications. Closed claims showed greater sensitivities (50.0-95.3%) than open claims (14.3-54.8%), with infusions having higher sensitivities than orals. PPVs were high for both infusions (closed: 79.1-98.3%; open: 61.5-99.1%) and orals (closed: 84.5-94.2%; open: 91.8-96.8%). Exact matches for abstracted infusion start dates in claims ranged from 45.5-82.5% for closed claims, while 27.6-65.9% of oral start dates matched within 7 days. The team concludes that while EHR remains the gold standard, individual claims may be sufficient for identifying patients receiving specific treatments, and closed claims may be suitable for constructing comprehensive treatment journeys.
Poster Presentation: Impact of NGS Testing Timing on Treatment Patterns and Clinical Outcomes in Colorectal Cancer
Date/Time: Thursday, May 15; 4:00 PM – 7:00 PM ET
Location: Exhibit Hall 220B-E, Poster #6013

Overview: Researchers evaluated the impact of next-generation sequencing (NGS) timing on real-world overall survival (rwOS) in 2,293 colorectal cancer (CRC) patients using the Tempus real-world multimodal database. The median age at diagnosis was 58.4 years, with most patients having stage 3 (23%) or stage 4 (68%) disease and receiving first-line (1L) chemotherapy without NGS-informed therapy. Time from biopsy to NGS test order was analyzed, revealing a notable delay in ordering NGS tests post-biopsy. A random forest classifier identified the timeline from biopsy to NGS results receipt as key in determining 1L treatment. Notably, stage 4 patients receiving NGS results within approximately two months of biopsy had a significant survival advantage. The study demonstrates that NGS testing may be associated with increased rwOS in CRC, highlighting the importance of timely NGS for guiding treatment decisions and improving outcomes.
Poster Presentation: Integrating Next Generation Sequencing, EHR, and Claims Data to Extend Follow-Up in a Real-World Advanced Lung Adenocarcinoma Biomarker-Treatment Landscape
Date/Time: Friday, May 16; 9:00 AM – 11:30 AM ET
Location: Exhibit Hall 220B-E, Poster #6046

Overview: The research team explored the use of closed claims data to enhance electronic health record (EHR)-derived treatment histories for stage 4 lung adenocarcinoma patients with comprehensive genomic profiling (CGP) and a diagnosis between 2020 and 2023. By linking closed claims data to EHRs, researchers extended abstracted lines of therapy (LOTs), defining new LOTs based on treatment gaps, persistent treatments, and follow-up duration. Integrating claims data increased the number of patients in LOT1, LOT2, and LOT3 and extended LOTs previously lost to follow-up. The integrated LOTs reflected NCCN guidelines, with EGFR inhibitors frequently used in EGFR-mutated patients and immunotherapy and KRAS inhibitors used in KRAS p.G12C patients. The study concludes that using closed claims to extend EHR-abstracted treatment data is valuable for real-world treatment pattern and outcome analyses.