TEST:

NeXT Personal™

P=Obs | N=814 | TRACERx (NCT01888601) | "Personalis...announced findings presented this week at the European Society of Medical Oncology Congress...In the first of these studies, Professor Charles Swanton and his colleagues...analyzed over 400 non-small cell lung cancer (NSCLC) patients from their TRACERx lung cancer study, using the NeXT Personal assay...A high percentage of these landmark detections (42%) occur in the ultrasensitive range (less than 80 ppm) enabled by NeXT Personal...In the second abstract, Dr. Rodrigo Toledo...presented data on a large cohort of over 200 late-stage cancer patients on immunotherapy profiled using the NeXT Personal assay, significantly expanding on the initial cohort first presented earlier this year. The study was unique in having a validation set of patients and it demonstrated that patients who had a significant decrease in ctDNA levels in response to immunotherapy had significantly longer overall survival than those who did not."

Early ctDNA dynamics determined by ultra-sensitive assay are predictive of long-term ICI response in the advanced, pan-cancer setting. ctDNA analyses emerges as a potential clinically useful tool for dealing with the ICI-related pseudoprogression phenomena.

We explored ultra-sensitive ctDNA detection in the largest cohort of relapsing NSCLC patients published to date, including its use for patient stratification and early detection of disease relapse. We observed that landmark positivity and ctDNA clearance were prognostic of patient outcome, including below 80 PPM. These results have implications for the advancement of personalised treatment strategies for NSCLC patients.

"Personalis, Inc...announced that the company has filed a second patent infringement suit against Foresight Diagnostics Inc. Personalis is seeking injunctive relief and monetary damages. This suit brings the total number of patents that Personalis alleges Foresight Diagnostics has infringed to seven."

No abstract available

"Personalis, Inc...announced...that data presented at the American Society for Clinical Oncology (ASCO) oral podium talks in Chicago, IL demonstrated that the Personalis NeXT Personal test had exceptional detection rates and performance for early-stage breast cancer and immunotherapy monitoring. The NeXT Personal test is the first of a new class of ultra-sensitive liquid biopsy tests designed to detect the earliest traces of cancer recurrence and monitor a patient’s response to therapy. The test can detect circulating tumor DNA (ctDNA) down to an ultra-sensitive range (<100 parts per million of ctDNA) and the data presented as ASCO highlights the clinical importance of this approach."

"Tempus...today announced the clinical launch of its minimal residual disease (MRD) test portfolio, including Tempus’ xM test and the xM (NeXT Personal Dx) test by Personalis. The portfolio features both a tumor-naïve assay and a tumor-informed assay that are designed to help detect residual disease or early cancer recurrence and monitor for immunotherapy treatment response, providing valuable insights to inform patient management strategies. The addition of both assays further complements Tempus’ comprehensive testing portfolio....xM was developed using the company’s multimodal database and advanced machine learning algorithms to accurately classify tumor fragments from non-tumor fragments, enhancing the precision of MRD calls."

"Personalis, Inc...announced...that two podium presentations and multiple posters featuring data for the company’s NeXT Personal® whole genome-based, tumor-informed assay for ultra-sensitive ctDNA detection will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, which convenes from May 31-June 4, 2024, in Chicago, Illinois."

Investor Presentation

Preliminary results from our prospective study demonstrate strong rates of ctDNA detection at week 4 landmark analysis, potentially due to detection of very low levels of ctDNA with an ultra-sensitive MRD assay. The majority of the first detections for MRD were in the ultra-low ctDNA range, indicating the importance of high sensitivity MRD testing.

We demonstrate that early ctDNA dynamics are predictive of long-term ICI response in the advanced, pan-cancer ECT setting. Even in this refractory advanced cancer cohort, an ultra-sensitive assay was required for accurate MRD status determination, with low ctDNA detections down to 4.2 PPM that might otherwise have been missed. Taken together, these findings suggest a high sensitivity ctDNA assay is crucial for accurate monitoring of ICI response, providing information for more accurate patient management.

The KeyLargo trial (NCT03342937) was a single-arm phase II study of pembrolizumab combined with oxaliplatin and capecitabine in first line HER2 negative mEGC patients (pts). ctDNA was detected in all pts at baseline. A decrease in ctDNA levels prior to the first restaging or ctDNA clearance up to cycle 7 were strong predictors of improved patient outcomes. ctDNA-based molecular progression predated progression by imaging by nearly two months, and ctDNA dynamics correlated with changes in tumor diameter.

NeXT Personal detected breast cancer relapse with a long lead-time over clinical relapse, and strongly associated with relapse free survival. The assay demonstrated high rates of ctDNA detection at diagnosis. The strong negative predictive value at landmark suggests potential use in de-escalation studies.

In this population of moderate risk (mostly stage II) HER2+ BC pts, 92% were ctDNA+ at BL. Neoadjuvant THP was very effective at clearing MRD, regardless of whether there was residual disease in the breast/nodes or not, consistent with the absence of any BC recurrence in the cohort to date.

"Personalis, Inc...announced today that a podium talk and multiple abstracts featuring data for the company’s NeXT Personal whole genome-based, tumor-informed assay for ultra-sensitive ctDNA detection will be presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place in San Diego, California, April 5-10, 2024."

"Personalis, Inc...today announced a new publication validating the company’s NeXT Personal test, an ultra-sensitive, tumor-informed circulating tumor DNA (ctDNA) assay. NeXT Personal is designed to help detect minimal residual disease (MRD), monitor therapy response, and identify recurrence with high analytical sensitivity and accuracy, enhancing the decision-making process and ultimately improving patient outcomes in the ongoing battle against cancer....In the analytical validation study published in Oncotarget, scientists from Personalis evaluated NeXT Personal by testing samples from over 120 patients across nine cancer types and paired tumor and normal cell lines. The NeXT Personal technology leverages whole genome sequencing (WGS) and advanced noise suppression with NeXT SENSE technology to identify a unique genetic signature derived from a patient’s tumor based on up to ~1,800 variants."

The assay targets 99.9% specificity, with this validation study measuring 100% specificity and in silico methods giving us a confidence interval of 99.92 to 100%. In summary, this study demonstrates NeXT Personal as an ultra-sensitive, highly quantitative and robust ctDNA assay that can be used to detect residual disease, monitor treatment response, and detect recurrence in patients.

Our findings suggest that ctDNA changes arepredictive of ICI response in late stage melanoma. These results highlight the potential for patient-specific ctDNA monitoring to inform patient management and for clincal trial design.

This approach addresses all parts of an MRD assay for both the plasma and tumor/normal tissues, utilizing real clinical samples while allowing direct interrogation of sensitivity. The Personalis NeXT Personal assay shows ultra-high sensitivity with reproducible data down to the 1-3 PPM range.

The assay also demonstrated strong performance across varying cfDNA input amounts from 2 ng to 30 ng. These studies demonstrate that NeXT Personal is an ultra-sensitive, highly specific, quantitative and robust assay, giving it the potential to detect residual disease and recurrence earlier than less sensitive assays.

NeXT Personal®, an ultra-sensitive tumor-informed ctDNA assay was used to longitudinally track ctDNA in advanced hepatocellular carcinoma (HCC) patients treated with GNOS-PV02 (a personalized therapeutic DNA cancer vaccine) in combination with pembrolizumab.Advanced unresectable or metastatic HCC patients that progressed on, or were intolerant to, first-line TKI therapy were enrolled into the Phase 1b/2a GT-30 study [NCT04251117]. ctDNA clearance was observed in all 3 CR patients with a lead time of 483, 126 and 105 days compared with MRI.This ultra-sensitive ctDNA assay shows significant association between ctDNA change and clinical response and survival, and can be used to accurately predict clinical outcome. The convenience of non-invasive liquid biopsy and rapid availability of data could enable the use of ctDNA to allow real-time monitoring of personalized cancer immunotherapy.

P=N/A; N=422; Recruiting; Sponsor:Personalis Inc.

Investor Presentation

"Personalis, Inc...and Tempus Labs, Inc...announced a strategic collaboration to co-commercialize NeXT Personal® Dx, Personalis’ whole genome-based liquid biopsy laboratory developed test (LDT) for detection of molecular residual disease (MRD) and recurrence in cancer. NeXT Personal Dx is a leap forward in tumor-informed approaches, setting the new standard in performance of MRD tests with unprecedented sensitivity and high specificity. The test was launched by Personalis in October of this year."

"Personalis, Inc...announced...the launch of the Early Access Program for NeXT Personal Dx, a tumor-informed, whole genome-based liquid biopsy laboratory developed test (LDT) for detection of molecular residual disease (MRD) and recurrence in cancer. Designed to help oncologists detect cancer recurrence earlier and aid in treatment decision-making, NeXT Personal Dx is poised to reshape the clinical use of MRD testing by delivering unmatched sensitivity down to the level of one circulating tumor DNA (ctDNA) molecule in a million."

"Personalis, Inc...announced the presentation of initial findings from its work with the groundbreaking TRACERx lung cancer study, marking a substantial advancement in lung cancer circulating tumor DNA (ctDNA) detection and management. The Personalis NeXT Personal cancer assay, created to detect and monitor residual and recurrent disease (MRD), demonstrated significantly improved detection rates for early-stage lung cancer, including lung adenocarcinoma (LUAD), one of the most common and challenging subtypes of non-small cell lung cancer (NSCLC) to identify in blood samples."

"Personalis, Inc...announced that a late-breaking abstract featuring data for the company’s NeXT Personal® whole genome-based, tumor-informed assay for ultra-sensitive ctDNA detection, has been accepted and selected for a proffered paper presentation at the 2023 European Society for Medical Oncology (ESMO) Congress, on October 21 in Madrid, Spain."

Critically, LUAD patients with ctDNA present at below 80 PPM (the 95% limit of detection for our recently published ctDNA detection approach in TRACERx) experienced reduced OS compared to those in which ctDNA was not detected (p=0.002, HR=12.2). Conclusions Our ultra-sensitive approach demonstrates superior analytic performance and prognostic prediction compared to other assays previously clinically validated in non-small cell lung cancer and provides an advanced stratification tool to guide adjuvant therapy in early-stage ctDNA-positive disease at high risk of relapse.

"Personalis, Inc. (Nasdaq: PSNL) today announced it will present new clinical data as scientific posters at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023, which convenes from June 2-6, 2023, in Chicago, Ill....At ASCO, Personalis will present data from two retrospective clinical studies that demonstrate a breakthrough in ctDNA detection sensitivity."

"Personalis, Inc...and Ono Pharmaceutical Co., Ltd. today announced they have entered into a collaborative agreement to examine the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for resectable rectal cancer with mismatch repair deficiency (dMMR). As part of the collaboration on the VOLTAGE-2 study, an exploratory analysis will be conducted to evaluate specific biomarkers such as minimal residual disease (MRD) status that may have prognostic or predictive value for patient care. Under the agreement, National Cancer Center Hospital East (NCCHE) will recruit patients and conduct the clinical trial, Ono will provide nivolumab, and Personalis will perform MRD and biomarker testing."

"Personalis, Inc...announced it has partnered with the Academic Breast Cancer Consortium (ABRCC) and Criterium to carry out a prospective clinical trial, B-STRONGER-1 (Breast Cancer-Minimal Residual Disease Detection and Therapy Monitoring in Patients with Early Stage TNBC-Phase I), to evaluate the clinical performance of the NeXT Personal^® test for detecting minimal residual disease (MRD) during and after treatment and recurrent cancer in patients with early-stage resectable triple-negative breast cancer (TNBC)."

The large healthy donor screening study demonstrated that our assay maintains excellent specificity and repeatability while still achieving ultra-sensitive detection. In all cases, the observed error-rates in the panels were very low and did not affect detection specificity. Overall these landmark specificity and repeatability results lend further confidence to the robustness of the analytical performance of NeXT Personal.

We used an ultra-sensitive, tumor-informed ctDNA platform to longitudinally track tumor neoantigen targets and monitor molecular residual disease (MRD) in advanced HCC patients (pts) being treated with a DNA personalized therapeutic cancer vaccine (GNOS-PV02). Highly sensitive tracking of MRD and neo-antigenic variants over the course of therapy was achieved using a single assay. We show that ctDNA can sensitively monitor disease status non-invasively, potentially leading to accurate clinical outcome prediction. Additionally, the ease of sample handling, analysis, and rapid availability of data could enable the use of ctDNA monitoring to allow real-time dynamic personalized cancer immunotherapy.

The MATRIX plasma-in-plasma approach is a robust option for assessing the sensitivity of MRD assays to low levels of ctDNA. This approach addresses all parts of an MRD assay for both the plasma and tumor/normal tissues, and is the closest thing to real clinical samples while allowing direct interrogation of sensitivity. Additionally, it allows assessment of any genomic or epigenomic biological feature.

We tracked both tumor-informed MRD and tumor-agnostic evolution of ICI related variants over the course of treatment using a single liquid biopsy platform. We achieved ultra-sensitive ctDNA detection down to 2.3 PPM and dynamics in ctDNA signals were predictive of clinical outcome. Furthermore, we demonstrated that ctDNA measurements and VAF dynamics of clinically actionable and resistance variants correlated with response as well as resistance to ICI.

KeyLargo (NCT03342937) was a single arm phase II study of pembrolizumab in combination with oxaliplatin and capecitabine in the first line treatment of patients (pts) with HER2 negative mEGC. ctDNA was present in all pts at baseline; OT PPM reductions correlated with PFS and best overall response. CAV profiling suggested a de novo PIK3CA variant arising during therapy in one patient. These findings suggest that tumor-informed plasma-based ctDNA profiling in mEGC may detect known CAVs arising during therapy, and with subsequent investigations, may inform therapeutic decisions.

"Personalis, Inc....Cancer Research UK’s Cancer Research Horizons, University College London (UCL), and the Francis Crick Institute...announced a collaboration to deploy NeXT Personal, a personalized liquid biopsy-based research assay, for the TRACERx study, a groundbreaking lung cancer initiative funded by Cancer Research UK."

"The data highlights the power of the company’s highly-discerning technologies that both characterize and monitor cancer, including initial research findings from a collaboration with University Medical Center Hamburg-Eppendorf (UKE) and its new Fleur-Hiege Center for Skin Cancer Research, where Dr. Klaus Pantel, Dr. Christoffer Gebhardt, and team are using NeXT Personal® to track tumor response to immunotherapy (IO) in patients with melanoma, with the aim of gathering evidence to advance the use of ultra-sensitive minimal residual disease (MRD) detection in routine clinical practice for IO therapy monitoring."

The assay is sufficiently sensitive for early stage, low shedding, and low TMB cancers, early time points or samples with limited input. The addition of clinically relevant tumor-agnostic actionable content makes NeXT Personal unique in its ability to detect MRD and to ultimately help guide clinicians.

Advanced melanoma patients exhibit a wide range of ctDNA concentrations at the beginning and during the course of treatment. Ultra-sensitive ctDNA detection down to 2.3 PPM was achieved using the NeXT Personal platform. Most importantly, our pilot study indicates that ctDNA measurements correlated with clinical outcome.

"Personalis...announced it will continue its collaboration with AstraZeneca...to explore ultra-sensitive molecular residual disease (MRD) measurement, including clinically relevant and personalized variant tracking, for clinical research and drug development...As part of the collaboration, Personalis’ NeXT Personal assay for liquid biopsy will aim to provide ultra-sensitive measurement of MRD, on-treatment therapy resistance tracking, and better differentiation between responders and non-responders, as well as investigate the underlying mechanisms driving cancer."

Investor Presentation: Submission of first indication for Medicare coverage in ‘24