On April 11, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported new data demonstrating the ability of the company’s investigational next-generation Guardant SHIELD multi-cancer assay to accurately detect early-stage cancers (Press release, Guardant Health, APR 11, 2022, View Source [SID1234612001]). This assay is designed to analyze approximately 20,000 epigenomic biomarkers that are informative for detection of a wide range of solid tumors in a single blood test . The data for four cancer types were demonstrated as examples: colorectal, lung, pancreatic and bladder. These cancers alone account for more than 200,000 cancer-related deaths in the U.S. annually.1 In addition, the blood test identified the tumor tissue of origin with high accuracy. These data were presented during an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

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Data from the presentation show that the next-generation Guardant SHIELD multi-cancer screening assay achieved sensitivity (detection rates) of 90% (n=692) in stages I and II colorectal cancer (CRC) and 87% (n=55) in stages I and II lung cancer. For more advanced cancer (stages III and IV), sensitivity was 93% (n=582) for CRC and 93% (n=136) for lung cancer. Detection was assessed at 90% specificity (true negative rates) based on a cohort of patients without cancer. This performance is on par with current guideline-recommended screening methods. Current screening options for these cancers, while effective, are limited due to low compliance rates: 66% for CRC and 14% for lung cancer.2,3 A high-performance blood test that can be completed as part of a routine patient workup has the potential to improve screening rates and, ultimately, save more lives.

In addition, the multi-cancer screening assay achieved sensitivity of 73% (n=11) in stages I and II pancreatic cancer and 52% (n=23) in stages I and II bladder cancer. For more advanced cancer (stages III and IV), sensitivity was 84% (n=31) in pancreatic cancer and 85% (n=61) in bladder cancer. Since there is no screening paradigm or diagnostic pathway for these cancers, a specificity threshold of 95% was targeted to reduce false positive rates while ensuring sensitivity is clinically impactful.

Highly accurate tumor tissue of origin prediction is needed when more than one cancer type is evaluated as part of a single assay to help direct patients to the most effective follow up for a positive test. The tumor tissue of origin prediction was evaluated at 98% specificity and correctly identified the tumor tissue of origin in 99% of colorectal, 94% of lung, 88% of bladder, and 86% of pancreatic cancers.

"These positive results show that the next-generation Guardant SHIELD multi-cancer assay provides sensitive detection of early-stage cancers with the ability to identify the tumor tissue of origin with high accuracy," said AmirAli Talasaz, Guardant Health co-CEO. "Presentation of these positive results represents a major step forward in our commitment to offering clinicians and patients a highly sensitive blood-based multi-cancer screening test in select tumor types where we believe cancer screening can save lives."

The investigational next-generation Guardant SHIELD multi-cancer test aims to detect early-stage cancer where there is a clinical benefit from early detection and treatment. In January 2022, Guardant Health initiated the SHIELD Lung study, a prospective, observational, multi-center basket study designed to enroll individuals undergoing cancer screening across multiple cancer types. The first cohort, or basket, will enroll nearly 10,000 individuals eligible for lung cancer screening and aims to evaluate the performance of the next-generation Guardant SHIELD test to detect lung cancer in high-risk individuals ages 50-80. The study is anticipated to run in approximately 100 centers in the United States and Europe. Additional information about the study is available at clinicaltrials.gov (NCT05117840).

On April 11, 2022 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported that updated data from its ongoing Phase 1/2 TRESR (Treatment Enabled by SNIPRx) clinical trial of RP-3500, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase) for the treatment of solid tumors with specific synthetic-lethal genomic alterations including those in the ATM gene (Ataxia-Telangiectasia mutated kinase) at the 2022 AACR (Free AACR Whitepaper) Annual Meeting (Press release, Repare Therapeutics, APR 11, 2022, View Source [SID1234612000]).

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"We see promising monotherapy data across tumor types, particularly in advanced ovarian cancer where 90% of patients had failed previous treatment with PARP inhibitors and platin based therapy. We are especially pleased with the 25% overall response observed, the clinical benefit rate of 75% and a median PFS of 35 weeks in this heavily pre-treated patient population with a growing unmet need," said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. "These findings, together with anticipated initial data of RP-3500 in combination with PARP inhibitors or gemcitabine expected in the second half of this year, will help us refine our development strategy for this potential best-in-class drug."

The data were featured today at the AACR (Free AACR Whitepaper) Annual Meeting in an oral presentation titled, "Genomic and pathologic determinants of response to RP-3500, an ataxia telangiectasia and Rad3-related inhibitor, in patients with DNA damage repair loss-of-function mutant tumors in the Phase 1/2 TRESR trial" (abstract number CT030).

"The data presented today continue to demonstrate RP-3500’s promising clinical benefit given as monotherapy in patients with solid tumors with multiple genotypes, as predicted by our SNIPRx platform, as well as a potential industry-leading safety and tolerability profile for ATR inhibitors," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "Our comprehensive new dataset shows ATM loss of function as a compelling opportunity to offer durable clinical benefit to patients with genetically defined tumors. Additional results beyond ATM, such as the early efficacy seen in other genotypes involving BRCA1/2, SETD2 and RAD51C alterations, represent substantial validation of our STEP2 platform to identify other synthetic lethalities as we expand TRESR and develop our pipeline of synthetic lethal candidates."

The Company will subsequently host a conference call today, April 11th at 6:30 p.m. Eastern Time to discuss the latest results from the TRESR trial.

Key Initial Findings from the TRESR Phase 1/2 Study:

TRESR is a first-in-human, multi-center, open-label Phase 1/2 dose-escalation and expansion study, designed to establish the recommended Phase 2 dose (RP2D) and schedule, evaluate safety and pharmacokinetics and identify preliminary anti-tumor activity associated with RP-3500, given alone and in combination with talazoparib. The study also examined biomarker responses and their relationship with response to RP-3500 treatment.

The oral presentation described monotherapy Phase 1 (Module 1) results from 120 patients, of which 99 patients were evaluable for efficacy, including 95 patients at RP2D of 160mg and schedule taken weekly for 3 days on/4 days off, and reflecting a data cutoff of 14th February, 2022. Key highlights from the data presented at the 2022 AACR (Free AACR Whitepaper) Annual Meeting include:

RP-3500 monotherapy continues to appear safe and well tolerated. Expectedly, Grade 1-2 anemia was the most common treatment-related adverse event and well controlled in patients. Only 24.2% of all patients in the 3 days on 4 days off schedule experienced Grade 3 anemia, and none Grade 4 anemia.
RP-3500 monotherapy resulted in durable clinical benefit across tumor types and genomic alterations. Overall clinical benefit rate (CBR) for all patients was 43%, and 47% in patients after PARP inhibitor (PARPi) failure.
Promising results were observed particularly in patients with advanced ovarian cancer (n = 20). 90% of evaluated patients had prior PARPi failure, and 85% of evaluated patients were platinum resistant. In these patients, overall response (OR) was 25%, including one complete response (CR), three partial responses (PR) as determined by RECIST 1.1 criteria, and one durable and ongoing CA125 response. CBR was 75% and median progression-free survival (mPFS) was 35 weeks.
Clinical benefit was also observed in patients with tumors harboring BRCA1 and BRCA2 genomic alterations, as predicted by SNIPRx. In patients with BRCA1/2 mutated tumors (n = 37), ORR was 14% and included two patients with ovarian cancer, and one each with breast cancer, head and neck squamous cell carcinoma, and melanoma. CBR was 43% with a mPFS of 15 weeks in the BRCA1/2 population; in patients specifically with BRCA1 mutations, the CBR was 48%.
In patients with ATM loss-of-function (LOF) tumors (n = 34), ORR was 9% including one RECIST 1.1 confirmed/unconfirmed response, and two prostate specific antigen (cPSA) responses. CBR in patients with ATM LOF was 44%, with mPFS of 17 weeks.
New sequencing data demonstrated biallelic gene LOF, an emerging biomarker for synthetic lethal therapies, can potentially be leveraged to further enrich for patients most likely to benefit from RP-3500. CBR in patients with biallelic LOF was significantly higher (47%) compared to the CBR in patients with non-biallelic tumors (15%).
A second poster presentation titled, "Detection of biallelic loss of DNA repair genes in formalin-fixed, paraffin embedded (FFPE) tumor samples using a novel tumor-only sequencing panel with error correction" (abstract number 2801) will be presented on Tuesday, April 12, 2022. Results demonstrated the role of SNiPDx, a central next-generation sequencing assay, in determining biallelic LOF, germline status and clonal hematopoiesis of indeterminate potential (CHIP) alterations, in patients enrolling in the TRESR study.

Company Conference Call:

The Company will host a conference call with accompanying slides for analysts and investors today at 6:30 p.m. Eastern Time to further discuss the RP-3500 data presented at the 2022 AACR (Free AACR Whitepaper) Annual Meeting. Repare’s executive management team will be joined by Timothy Yap, MBBS, PhD, FRCP, Principal Investigator and Medical Director, Institute for Applied Cancer Science, Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX.

To access the call, please dial (877) 870-4263 (U.S. and Canada) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined to the Repare Therapeutics call. A live video webcast will be available in the Investor section of the Company’s website at View Source A webcast replay will also be archived for at least 30 days.

About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On April 11, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) reported that the U.S. Food and Drug Administration (FDA) lifted the partial clinical hold placed on studies evaluating its investigational agent magrolimab in combination with azacitidine (Press release, Gilead Sciences, APR 11, 2022, View Source [SID1234611999]). The FDA removed the partial clinical hold after a review of the comprehensive safety data from each trial.

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With today’s decision from the FDA, enrollment in the U.S. can resume for the studies investigating magrolimab in combination with azacitidine in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Gilead, in close coordination with regulatory authorities, is planning to re-open enrollment in the magrolimab studies that were placed on a voluntary hold outside of the U.S. The company is also working with the FDA regarding the remaining partial clinical hold affecting studies evaluating magrolimab in diffuse large B-cell lymphoma and multiple myeloma. The ongoing clinical studies evaluating magrolimab in solid tumors were not subject to the clinical hold.

"Our confidence in the risk-benefit profile of magrolimab has been unwavering, and we continue to believe in the potential for this treatment to address the unmet medical needs faced by people living with MDS and AML," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "This is a significant milestone for Gilead and, more importantly, for patients diagnosed with these cancers. We look forward to continuing our work developing magrolimab and advancing this potential cancer treatment option."

During the partial clinical hold, patients already enrolled in the affected Gilead magrolimab studies, including the pivotal, Phase 3 ENHANCE study, continued receiving treatment. Prior to the trial hold, Gilead already met the pre-specified enrollment threshold required for the first interim analysis of the ENHANCE study. Based on this, Gilead is confident the readout for the first interim analysis remains on schedule for 2023.

Magrolimab was granted Breakthrough Therapy designation for the treatment of newly diagnosed MDS by the FDA in 2020. In addition to MDS and AML, magrolimab is being developed in several hematologic cancers and solid tumor malignancies. Magrolimab is an investigational product and is not approved by any regulatory authority for any use; its safety and efficacy have not been established.

About Myelodysplastic Syndrome (MDS)

MDS is a rare, often unrecognized, under-diagnosed, bone marrow disorder widely considered to be a form of cancer. In MDS, the body’s bone marrow does not make enough mature, healthy red blood cells, white blood cells and/or platelets. While many cases may go undiagnosed, current estimates show that ~100,000 new cases are diagnosed each year. Therapeutic advancement for higher-risk MDS has been limited in the last 15 years and stem cell transplant is the only potential cure, but those older than 65 or with other conditions are often not eligible.

One in three people with MDS will progress to AML, one of the most common types of leukemia in adults. Approximately 10,000 people die every year from AML in the U.S.

About Acute Myeloid Leukemia (AML)

AML is a type of cancer that starts in the bone marrow and can quickly move to the blood and other parts of the body, including the lymph nodes, spleen and central nervous system. AML most often develops from cells that would turn into red blood cells, neutrophils, and platelets but can also evolve from other blood disorders such as myelodysplastic syndromes. Approximately 20,000 Americans will be diagnosed with AML each year.

About Magrolimab

Magrolimab is a potential, first-in-class investigational monoclonal antibody against CD47 and a macrophage checkpoint inhibitor that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, with the goal of blocking the "don’t eat me" signal used by cancer cells to avoid being ingested by macrophages. Magrolimab is being developed in several hematologic cancers, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) as well as solid tumor malignancies. More information about clinical trials with magrolimab is available at www.clinicaltrials.gov.

On April 11, 2022 Biognosys, a leader in next-generation proteomics solutions for drug discovery and development, reported a global strategic partnership agreement with NeoGenomics, Inc. (Nasdaq: NEO), a leading provider of oncology testing and global contract research services (Press release, Biognosys, APR 11, 2022, View Source [SID1234611998]). The strategic partnership will encompass multiple strategic and commercial initiatives, including NeoGenomics labs offering access to Biognosys proteomics platforms, medical and scientific affairs-joint presentations and discussions, along with joint scientific and technical initiatives.

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"At Biognosys, we continuously push the boundaries of what is possible with our proteomics solutions to address key challenges in drug development," said Kristina Beeler, Ph.D., Chief Business Officer, Biognosys. "Our platforms are transforming research from early drug discovery to clinical biomarker identification. We are excited to now combine our proteomics platforms with NeoGenomics’ immuno-profiling platform to advance our biopharma partners’ oncology drug development programs."

One of the first efforts of this collaboration saw Biognosys combining its TrueDiscovery proteomics platform with NeoGenomics’ MultiOmyx multiplexed immunofluorescence (mIF) spatial tissue analysis as a multimodal approach for analyzing the proteins of tumor samples from late-stage melanoma patients treated with immune-checkpoint inhibitors. The dual proteomic and mIF profiling approach allows for a comprehensive characterization of melanoma patients and pinpointed a specific set of biomarkers that may be used to predict a patient’s response to checkpoint inhibitors. The development and utility of this multimodal approach will be presented across two posters by Biognosys and NeoGenomics at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting this week. The multimodal offering will also be made available commercially for biopharma partners.

"The need of our pharma customers to access the next state-of-the-art technology to improve diagnostics and clinical trials is top priority for us," said Gina Wallar, Ph.D., President, Pharma Services, NeoGenomics Laboratories, Inc. "Partnering with Biognosys gives us the added advantage of expanding into proteomics, data analytics and subsequent actionable results, not only in early discovery and translational research but ultimately, in clinical trials impacting patient care."

AACR Posters

Abstract 3923: Ubiquitin ligases implicated as predictive biomarkers for poor outcome to immunotherapy in melanoma patients

In this poster presented by Biognosys on April 13, unbiased proteomic profiling with TrueDiscovery was used to characterize melanoma patients and their responses to PD1-targeted immunotherapy. The profiling was able to identify a set of 103 proteomic biomarkers associated with ubiquitination pathways that correlate with treatment outcomes. The results were cross analyzed with the spatial tissue analysis performed via the MultiOmyx platform. These findings need to be further confirmed in orthogonal cohorts, nevertheless the data point to the possibility of more precise targeting of melanoma patients for immunotherapy.

Abstract 1267: Dual approach using unbiased proteomics and multiplexed immunofluorescence for the detection of markers predictive for immunotherapy in melanoma patients

Despite clinical advances, durable responses to immune checkpoint inhibitors are not observed in 40-60% of melanoma patients, and current biomarkers do not clearly distinguish responders. In this study presented by NeoGenomics today, a dual proteomic and mIF profiling approach was able to comprehensively characterize melanoma patients and successfully stratify non-responders from responders based on a set of selected protein biomarkers.

To see Biognosys’ full presence at the AACR (Free AACR Whitepaper) 2022 annual meeting, please refer to this press release or visit biognosys.com/aacr22.

On April 11, 2022 Bruker Corporation (Nasdaq: BRKR) reported that launched and exhibited unique and novel capabilities for spatial multiomics, single-cell proteomics, and cell-line, tissue and plasma proteomics cancer research (Press release, Bruker, APR 11, 2022, View Source [SID1234611997]).

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Following up on Bruker’s recent strategic investment in AmberGen Inc., Bruker is announcing a partnership for the application of Ambergen Miralys peptide-code antibody kits for the Bruker timsTOF flex novel MALDI HiPLEX-IHC workflow for targeted protein expression profiling in tissue. By combining peptide-code mass-reporting antibody probes for protein recognition with Bruker’s comprehensive MALDI imaging workflows, researchers can produce highly multiplexed images of target proteins in a wide field-of-view up to a standard slide.

Bruker’s timsTOF fleX platform integrates MALDI HiPLEX-IHC protein mapping with unbiased small molecule imaging (lipids, glycans, metabolites, xenobiotics) from the same tissue section, a new and unique multiomics capability for cancer cell-line, tissue and TME imaging research from fresh frozen or formalin-fixed paraffin-embedded (FFPE) sections.

Dr. Michael L. Easterling, Bruker Director of Imaging Life Sciences Mass Spectrometry, commented: "Spatial protein expression mapping can elucidate processes in immuno-oncology, and in TME and metastasis research. The MALDI HiPLEX IHC workflow based on AmberGen’s peptide-encoded antibody panels provides targeted protein localization and adds the capability to map important lipids, glycan and metabolite markers on the same tissue section.

Additionally, Bruker demonstrated the new CellScapeTM instrument for high-precision targeted spatial proteomics, recently launched by their Canopy Biosciences division. Canopy Biosciences’ CellScape is the latest generation ChipCytometryTM instrument, which enables high-plex spatial imaging and quantification of protein biomarkers in a wide variety of sample types with single-cell and sub-cellular resolution. CellScape further improves spatial resolution, offers up to 8x higher throughput, and walkaway automation. CellScape is unique for quantitative biology with 8-log extremely high dynamic range (HDR) imaging to quantify both low and high expressing proteins in the same sample, solving a key challenge inherent in high-plex imaging. Applications in cancer biology are abundant and include spatial phenotyping of the diverse tumor and immune cell types in the tumor microenvironment (TME).

Canopy also featured their Spatial Immune Profiling kits for the ChipCytometry platform. The Spatial Immune Profiling kit is a quantitative, multiplexed assay for FFPE tissues developed to provide ready-to-use pre-validated antibody reagents for ChipCytometry researchers, e.g., for immuno-oncology. The kits enable researchers to skip assay development and move straight into performing their translational and clinical research assays.