On January 8, 2025 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a life sciences company developing novel targeted oncology therapies and commercializing RenovoCath, a novel, FDA-cleared delivery platform, reported three abstracts were accepted to be presented at several upcoming industry conferences including ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) 2025, Society of Interventional Oncology (SIO) 2025 and Society of Surgical Oncology (SSO) 2025 (Press release, Renovorx, JAN 8, 2025, View Source [SID1234649528]).

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The abstracts support RenovoRx’s novel and patented TAMP therapy platform via additional human PK data and pre-clinical data. TAMP is designed to ensure precise therapeutic delivery across the arterial wall near the tumor site to bathe the target tumor, while potentially minimizing a therapy’s toxicities versus systemic intravenous therapy. RenovoRx’s novel approach to targeted treatment offers the potential for increased safety, tolerance, and improved efficacy.

RenovoRx’s pivotal ongoing Phase III TIGeR-PaC clinical trial is evaluating the Company’s first product candidate, a novel investigational oncology drug-device combination utilizing the Company’s FDA-cleared RenovoCath device via TAMP for the intra-arterial administration of chemotherapy, gemcitabine. RenovoRx currently anticipates completion of both patient enrollment and the second interim analysis for TIGeR-PaC by the end of the first half of 2025.

Abstract Details:

ASCO GI 2025

Title: Intra-arterial Gemcitabine Versus Intravenous Gemcitabine: Pharmacokinetic Sub-study of the TIGeR-PaC Phase 3 Clinical Trial
Authors: Paula Novelli MD, Amer Zureikat MD, Michael Pishvaian MD, Kenneth Meredith MD, Hassan Hatoum MD, Emmanuel Zervos MD, Reza Nazemzadeh MD, Sandeep Loria MD, Ramtin Agah MD
Location: Moscone West, San Francisco CA
Date/Time: January 24, 2025 at 11:30 a.m. PT
SIO 2025

Title: Micro-CT imaging following intra-arterial delivery of a radiopaque silicone polymer using a double-balloon occlusion catheter in pigs: a model to analyze tissue penetration via the trans-arterial micro perfusion (TAMP) technique
Authors: Paula Novelli MD, Christopher Laing MD, Aloke Finn MD, Frank Kolodgie PhD, Robert Strasser BSc, Ramtin Agah MD
Location: Horseshoe Las Vegas, Las Vegas NV
Date/Time: February 2, 2025 at 12:30 p.m. PT
SSO 2025

Title: Pharmacodynamics of Intra-arterial vs. Intravenous Gemcitabine in Locally Advanced Pancreatic Cancer: Results of a Phase III Randomized Clinical Trial
Authors: Emmanuel Zervos MD, Paula Novelli MD, Amer Zureikat MD, Michael Pishvaian MD, Kenneth Meredith MD, Hassan Hatoum MD, Reza Nazemzadeh MD, Sandeep Loria MD, Ramtin Agah MD
Location: Tampa Convention Center, Tampa FL
Dates: March 27 – 29, 2025
The abstracts accepted at ASCO (Free ASCO Whitepaper) GI 2025 and SSO 2025 are sub-studies of the ongoing Phase III TIGeR-PaC clinical trial.

"These abstracts support the potential for our TAMP therapy platform to provide a meaningful advancement in the standard of care for cancer treatment," said Ramtin Agah, MD, Chief Medical Officer and Founder of RenovoRx. "TAMP focuses on drug concentration optimization in tumors by delivering therapies with our RenovoCath delivery system. This targeted approach to cancer treatment is designed to enable physicians to isolate segments of the vascular anatomy closest to tumors and ensure precise therapeutic delivery, while potentially minimizing a therapy’s toxicities versus the standard of care. Specifically, our approach enables physicians to utilize RenovoCath to use pressure to force chemotherapy across the arterial wall near the tumor site to bathe the target tumor."

Dr. Agah added, "We also look forward to the completion of patient enrollment and our second interim analysis in our pivotal Phase III TIGeR-PaC clinical trial in LAPC by the end of the first half of 2025."

About RenovoCath

Based on its FDA clearance, RenovoCath is intended for the isolation of blood flow and delivery of fluids, including diagnostic and/or therapeutic agents, to selected sites in the peripheral vascular system. RenovoCath is also indicated for temporary vessel occlusion in applications including arteriography, preoperative occlusion, and chemotherapeutic drug infusion. For further information regarding our RenovoCath Instructions for Use ("IFU"), please see: IFU-10004-Rev.-F-Universal-IFU.pdf.

About the TIGeR-PaC Clinical Trial

TIGeR-PaC is an ongoing Phase III randomized multi-center study evaluating the proprietary TAMP (Trans-Arterial Micro-Perfusion) therapy platform for the treatment of Locally Advanced Pancreatic Cancer (LAPC.) RenovoRx’s first product candidate using the TAMP technology, is a novel investigational oncology drug-device combination utilizing the Company’s FDA-cleared RenovoCath device for the intra-arterial administration of chemotherapy, gemcitabine.

The first interim analysis in the Phase III clinical trial was completed in March 2023, with the Data Monitoring Committee recommending a continuation of the study. The study’s primary endpoint is an Overall Survival benefit with secondary endpoints including reduced side effects versus standard of care. The second interim analysis for this study will be triggered by the 52nd event (i.e., patient death), which is estimated to occur in late 2024 or early 2025. The second interim data readout would follow thereafter, with the timing for such readout depending on customary factors such as time needed for analysis. RenovoRx is also aiming to complete patient enrollment in the TIGeR-PaC study in the first half of 2025.

On January 8, 2025 Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine and patient care, reported a collaboration with Genialis, the RNA-biomarker company (Press release, Tempus, JAN 8, 2025, View Source [SID1234649527]). The multi-year agreement allows Genialis to leverage Tempus’ multimodal dataset to develop new RNA-based algorithms across cancer types.

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Clinical care for cancer patients is hindered by insufficient biomarkers that fail to accurately predict patient response to treatment. To address this, Genialis has developed an AI foundation model using data from ~1 million RNA-sequencing samples representing globally diverse patients. This large molecular model (LMM), dubbed the Genialis TM Supermodel, yields accurate and information-rich biomarker algorithms to help biopharma improve therapeutic development. Validating Genialis’ LMM using Tempus real-world multi-modal data is essential to demonstrate the clinical utility and broad applicability of these biomarkers in drug development and clinical practice. As part of the collaboration, Genialis can now leverage Tempus’ analytics platform, Lens, which provides a development platform accessing de-identified multimodal patient records and a suite of tools to validate signatures to accelerate the company’s efforts to bring its clinical algorithms to market. In return, Tempus gains the right to evaluate and potentially license Genialis-developed algorithms for commercialization as a component of the xR platform.

Tempus multimodal dataset has already proved pivotal in the launch of GenialiskrasID, the first commercially available algorithm that stratifies patients who benefit from KRAS inhibition. Presented at the 6th Annual Targeting-RAS Drug Development Summit in September 2024, Genialis krasID uniquely predicts patient response to KRAS-targeted therapies across cancer types and driver mutations. Independently validated using Tempus’ real-world data, Genialis krasID stratifies patients into high and low likelihood response groups that have been evaluated in real-world studies1,2.

"We look forward to working with Genialis and demonstrating new ways in which our data can be applied to further a new kind of research, one that embraces the power that RNA-based biomarkers can have on the future of cancer care," said Kate Sasser, Ph.D., Chief Scientific Officer at Tempus. "Multimodal algorithms, including RNA signatures, are demonstrating rapid advancement in clinical utility for personalized treatment decisions, and we are excited to partner with Genialis to fuel this data-driven precision medicine future with our xR assay and vast multimodal dataset."

"Biomarkers have the potential to transform how cancer is diagnosed and treated, but today’s standard of care leaves a lot to be desired in terms of accuracy, information richness, and patient reach," said Rafael Rosengarten, Ph.D., CEO of Genialis. "With this strategic agreement with Tempus, Genialis will have access to an unparalleled data resource to validate our cutting-edge patient classifiers."

On January 8, 2025 Vir Biotechnology, Inc. (Nasdaq: VIR) reported initial Phase 1 data from two of its dual-masked T-cell engagers (TCEs): VIR-5818, targeting a variety of HER2-expressing solid tumors; and VIR-5500, targeting PSMA in metastatic castration-resistant prostate cancer (mCRPC) (Press release, Vir Biotechnology, JAN 8, 2025, View Source [SID1234649526]). Data show encouraging preliminary safety and efficacy profiles with no dose-limiting cytokine release syndrome (CRS), maximum tolerated dose (MTD) not yet reached as dose escalation continues, and early clinical response signals observed in heavily pretreated participants. These initial results provide clinical support for Vir Biotechnology’s in-licensed PRO-XTEN masking technology, which is designed to enable the selective activation of TCEs in the tumor microenvironment, mitigating damage to healthy cells and reducing toxicity.

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"Overcoming the toxicity-driven limitations of traditional T-cell engagers could address an important unmet medical need in cancer care," said Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology. "Preliminary safety and efficacy data for our dual-masked T-cell engagers VIR-5818 and VIR-5500 are compelling, and we will continue dose escalation with an opportunity to expand the therapeutic window. We are encouraged that our candidates may enable efficacious and well-tolerated treatment regimens, potentially improving outcomes for people living with a range of solid tumors."

VIR-5818: PRO-XTEN Initial Proof-of-Concept and Potential First-in-Class HER2 Immunotherapy

Despite availability of HER2-targeting therapies, there remains a significant unmet need for treatments with novel mechanisms of action to improve tolerability and extend survival. Currently, no HER2-directed immunotherapies are approved for solid tumors. The preliminary safety and efficacy data of VIR-5818 support the tumor-specific activation of PRO-XTEN dual-masked TCEs and the potential of this technology to broaden the therapeutic index of TCEs.

VIR-5818 is being evaluated in a Phase 1 clinical trial (NCT05356741) designed to study its safety and pharmacokinetics alone, and in combination with pembrolizumab, in participants with a variety of HER2-expressing cancers, including breast and colorectal cancer (CRC). The study has enrolled 79 heterogeneous and heavily pretreated participants in monotherapy cohorts.

Early efficacy data indicate that 50% (10/20) of participants receiving VIR-5818 doses ≥400 µg/kg experienced dose-dependent tumor shrinkage across multiple HER2-positive tumor types. This includes participants who had received up to 9 prior lines of therapy. Strong anti-tumor activity was observed in a subset of participants with HER2-positive CRC who have exhausted standard of care. In this subset, confirmed partial responses (cPRs) were seen in 33% (2/6) of participants at early doses, and one patient continued in cPR for more than 18 months as of the data cut-off.

Preliminary safety data demonstrate that VIR-5818 is generally well-tolerated, with minimal grade 1 or 2 CRS (20% and 10%, respectively) and no grade 3 or greater CRS observed in any of the 79 participants across doses up to 1000 µg/kg. Most treatment-emergent adverse events (TEAEs) were low grade, reversible and manageable. The MTD has not yet been reached. Preliminary pharmacokinetics and safety data indicate low systemic unmasking of the TCE, suggesting tumor-specific activation. Dual masking results in a half-life of approximately 6 days, which may enable a less frequent dosing regimen. As a result, Vir Biotechnology is currently evaluating a Q3W dosing regimen.

VIR-5500: First Dual-Masked PSMA-Targeting TCE

Prostate cancer is the second most diagnosed cancer in men1. Despite advancements, there is still a significant unmet need for efficacious, well-tolerated treatments that can extend survival and improve quality of life.

VIR-5500 is being evaluated in a Phase 1 clinical trial (NCT05997615​) designed to assess its safety, pharmacokinetics, and preliminary efficacy in participants with mCRPC. The study has enrolled 18 participants with significant disease burden who have received 3 to 6 prior lines of therapy.

Early efficacy data show encouraging signs of prostate-specific antigen (PSA) responses, and PSA reductions were observed in 100% (12/12) of participants after an initial dose ≥120 µg/kg. PSA50 response was confirmed in 58% (7/12) of participants receiving a first dose ≥120 µg/kg.

Preliminary data show a promising safety profile, with no dose-limiting toxicities observed up to 1000 µg/kg without prophylactic corticosteroids. Safety findings showed minimal grade 1 or 2 CRS (17% and 11%, respectively) and no grade 3 or greater CRS at any dose. Most TEAEs were low grade. No hearing loss has been reported, suggesting safety benefits of dual masking in preventing on-target, off-tumor toxicities. Dose escalation is ongoing, and the MTD for VIR-5500 has not yet been reached. Preliminary pharmacokinetics and safety data indicate tumor-specific activation with minimal unmasking outside the tumor. The dual-masked TCE shows a desirable half-life of 8-10 days, which is enabling Vir Biotechnology to evaluate a Q3W dosing regimen. The safety and tolerability profile observed for VIR-5500 in ongoing dose escalation, together with the observed signs of early anti-tumor activity at low doses, may enable a wide therapeutic index.

About VIR-5818, VIR-5500, VIR-5525

VIR-5818, VIR-5500, VIR-5525 are investigational, clinical candidates currently being evaluated for the treatment of solid tumors. These assets leverage the PRO-XTEN masking technology with three different T-cell engagers (TCEs) targeting HER2, PSMA, and EGFR, respectively.

TCEs are powerful anti-tumor agents that can direct the immune system, specifically T-cells, to destroy cancer cells. The PRO-XTEN masking technology is designed to keep the TCEs inactive (or masked) until they reach the tumor microenvironment, where tumor-specific proteases cleave off the mask and activate the TCEs, leading to killing of cancer cells. By driving the activity exclusively to the tumor microenvironment, we aim to circumvent the traditionally high toxicity associated with TCEs and increase their efficacy and tolerability. Additionally, the mask is designed to help drug candidates stay in the bloodstream longer in their inactive form, allowing them to better reach the site of action and potentially allowing less frequent dosing regimens for patients and clinicians.

On January 8, 2025 Asher Biotherapeutics, a biotechnology company developing precisely-targeted immunotherapies for cancer and infectious diseases, reported a clinical trial collaboration and supply agreement with Amgen (NASDAQ:AMGN) to evaluate etakafusp alfa (formerly known as AB248), Asher Bio’s investigational CD8+ T cell targeted interleukin-2 (IL-2) immunotherapy, in combination with IMDELLTRA (tarlatamab), Amgen’s DLL3-targeting Bispecific T-cell Engager (BiTE) therapy, in patients with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Asher Biotherapeutics, JAN 8, 2025, View Source [SID1234649525]).

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"This clinical trial collaboration and supply agreement with Amgen allows us to further expand on the Phase 1 results for etakafusp alfa in a new combination with IMDELLTRA in a global Phase 1b study in ES-SCLC," said Don O’Sullivan, Ph.D., Chief Business Officer of Asher Bio. "Based on emerging data to date, we believe etakafusp alfa has the potential to improve the efficacy of T cell engagers (TCEs) by selectively expanding the CD8+ T cell population, improving effector function, tumor infiltration and reversing TCE-induced T cell desensitization. We look forward to collaborating with Amgen to assess the potential for the novel combination to improve outcomes for patients with ES-SCLC."

As part of this collaboration agreement, Amgen will sponsor and operationalize a global Phase 1b study to evaluate the safety and early efficacy of etakafusp alfa in combination with IMDELLTRA in patients with ES-SCLC. Asher Bio will retain full ownership of etakafusp alfa and will supply Amgen with etakafusp alfa at no cost.

About SCLC
SCLC is one of the most aggressive and devastating solid tumor malignancies, with a median survival of approximately 12 months following initial therapy and a 3% five-year relative survival rate for ES-SCLC.1,2,3 Current second-line treatments impart a short duration of response (median DoR: 3.3–5.3 months) and limited survival (median OS: 5.8-9.3 months), while current third-line treatments for SCLC, which consist primarily of chemotherapy, yield a short median DoR of 2.6 months and a median OS of 4.4-5.3 months.4-8 SCLC comprises ~15% of the 2.4 million plus patients diagnosed with lung cancer worldwide each year.9-11 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options.13

About Etakafusp Alfa (AB248)
Etakafusp Alfa (AB248) is a novel CD8+ T cell selective IL-2, generated by fusing a reduced potency IL-2 mutein to an anti-CD8β antibody. It was specifically engineered to selectively and potently activate CD8+ T-cells which are the immune cells that drive anti-tumor efficacy, while avoiding natural killer (NK) cells, which can act as a pharmacological sink and contribute to toxicity, and regulatory T (Treg) cells, which are immunosuppressive. Asher Bio is currently evaluating etakafusp alfa in a Phase 1a/1b clinical trial, AB248-101. The trial consists of a dose escalation and expansion phase to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of etakafusp alfa alone and in combination with pembrolizumab in subjects with locally advanced/metastatic solid tumors who failed prior therapies. Initial pharmacokinetic and pharmacodynamic data from the ongoing Phase 1a/1b clinical trial support etakafusp alfa’s proof of mechanism and activity with a highly differentiated clinical profile. Early data shows potent and selective CD8+ T cell activation without substantial changes to Treg and NK cell numbers and initial evidence of anti-tumor activity, including confirmed objective responses, with a generally well-tolerated safety profile. Please refer to www.clinicaltrials.gov (NCT05653882) for additional details related to this Phase 1a/1b clinical trial.

On January 8, 2025 Ambry Genetics, a leader in clinical genomic testing, reported its contribution to a study published in Nature that significantly advances our understanding of BRCA2 gene variants (Press release, Ambry Genetics, JAN 8, 2025, View Source [SID1234649524]). As the uptake of genetic testing continues to grow, the need for scalable interpretation of the vast number of variants detected has become critical. This study was designed to leverage CRISPR/cas-9 gene editing to aid in the functional characterization of nearly 7,000 BRCA2 variants, helping to resolve variants of uncertain significance (VUS) and guide better clinical management.

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BRCA2 is a well-established and clinically actionable gene associated with cancer predisposition.1 Testing BRCA2 has long been a staple of hereditary cancer testing, as pathogenic variants in the gene are associated with cancers of the breast, ovary, prostate, and pancreas.2-5 Despite the well-understood importance of BRCA2, at the time of this research, more than 5,000 BRCA2 variants are categorized as VUS in the National Institute of Health’s (NIH) ClinVar database (a catalogue of genomic variants and their classifications). Many of these are classified as VUS because there has been insufficient evidence to their classification.6

The study, led by Fergus J. Couch, PhD, of Mayo Clinic, brought together an interdisciplinary team of researchers from Mayo Clinic, H. Lee Moffitt Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Hospital Clinico San Carlos, Memorial Sloan Kettering Cancer Center, and Duke University, as well as Ambry Genetics, to understand and evaluate BRCA2 variants for their functional contributions to cancer pathogenesis.

The results of this study were integrated into a ClinGen/ACMG/AMP model for clinical interpretation, resulting in a 91% rate of classification showing the promise for improving the future of hereditary cancer testing results across all test providers.

"These findings illustrate the power of integrating functional genetic data with clinical analysis to improve understanding of hereditary cancer risk and optimize clinical management approaches," said Marcy Richardson, PhD, Associate Director of Clinical Research at Ambry Genetics. "Functional testing of cancer-associated genes enables the clinical community to offer patients better data-informed recommendations on how best to mitigate cancer risk."

"These findings demonstrate the value of collaborative research in advancing our understanding of BRCA2 variants, improving classification methods that support more accurate risk assessments and informed clinical care," said Fergus Couch, Ph.D., Professor at Mayo Clinic and lead author of the study. "By integrating functional studies with clinical data, we can provide clinicians with valuable tools to guide patients in managing their hereditary cancer risks."

"Genetic testing and variant analysis are paving the way towards truly personalized clinical care for patients before they have cancer, moving us well beyond the time when clinical decision-making based on family history left many clinicians and patients feeling powerless to intervene prior to cancer onset," said Elizabeth Chao, MD, FACMG, Chief Medical Officer at Ambry Genetics. "Improving the quality of data available in our genetic databases allows us to better classify variants across diverse populations, offering a more inclusive approach to genetic testing, giving clinicians new tools for recommending measures to prevent cancer."

This paper is co-published alongside another related study with the NIH, which examines the same issues using a different model. Together, these studies represent a major step forward in variant classification, providing essential data that helps clinicians better assess cancer risks tied to genetic mutations.