On April 9, 2024 Genialis, the RNA-biomarker company, reported a poster on a new AI/ML classifier, Genialis krasID, that accurately predicts clinical benefit in a real-world cohort of patients who received sotorasib, a KRAS inhibitor currently approved for KRAS G12C non-small cell lung cancers (Press release, Genialis, APR 9, 2024, View Source [SID1234641962]). Genialis presented additional findings on the performance of the biomarker in predicting drug response across preclinical models and real-world clinical benefit at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2024 Annual Meeting in San Diego on April 5-10, 2024.

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Genialis krasID analyzes foundational aspects of KRAS biology using RNA-sequencing and a machine learning algorithm comprising numerous biologic signatures. The classifier predicted preclinical drug response with an accuracy of 0.94 Area Under the Receiver Operator Curve (AUROC) and correctly selected real-world patient responders with an AUROC of 0.80. Kaplan-Meier analysis of the real-world sotorasib patient data considered time on treatment as an available proxy for progression-free survival. This analysis showed that patients classified as "krasID-high" had median time on treatment of almost one year (338 days), compared with those classified as "krasID-low" with median time on treatment of only 158 days (hazard ratio [HR] = 0.35). Taken together, these early results demonstrate that the Genialis krasID classifier can predict response and stratify durable benefit in experimental and clinical settings.

"Genialis krasID is designed to support the entire lifecycle of drug development and clinical care. Because the model incorporates biologies that are intrinsic to KRAS function in the tumor and extrinsic to the surrounding tumor milieu, we expect this biomarker to perform well for diverse drugs across disease settings and mutation status," said Mark Uhlik, Vice President of Biomarker Development at Genialis.

KRAS mutations are prevalent in many common oncologic malignancies, including lung, colorectal, and pancreatic cancers, with frequencies ranging from 25 percent in NSCLC to nearly 95 percent in pancreatic. Even with two FDA approvals of KRAS inhibitors, the rate of patient response (~30-40%) and the durability of responses (~10-11 months) leaves room for improvement. Most biomarkers in the KRAS space measure only KRAS mutation status, which may be necessary to receive the drug but is insufficient to predict or monitor response or to inform further therapeutic interventions. By using high-dimensional gene expression data, Genialis krasID captures underlying biological complexity unique to each individual patient.

"Genialis recognizes an urgent need for patients with lung, colorectal and pancreatic cancers to have access to more informative diagnostic tests that steer them to the best possible medicines for their disease," said Rafael Rosengarten, PhD, CEO of Genialis. "We’re just at the dawn of being able to treat KRAS-driven cancers. With Genialis krasID, we can provide the most complete picture of the diseases we’re trying to defeat, and a plan for how to win."

AACR marks the launch of an early access program (EAP) for Genialis krasID. Over 50 biopharma companies are currently developing more than 70 different KRAS-targeted drugs across over 12 disease indications. The total KRAS therapy market today is estimated at approximately $240 million, with a compound annual growth rate of 36% to reach $10 billion by 2032. Meanwhile, available diagnostics to support KRAS-targeted patient care are limited to mutation-based tests.

Last week, Genialis announced the addition of two new partners as it assembles the world’s most ethnographically diverse cancer data sets. For the new Genialis krasID program, Genialis already has commitments from several marquee partners across biopharma, diagnostics, and clinical research centers and is reserving space to add a handful more of select organizations. Early access program members will gain the opportunity to have their KRAS-related data analyzed by Genialis to establish a foundation for implementing krasID within their translational and clinical workflows. Genialis anticipates a full commercial launch of the biomarker product in September. For more information on Genialis RNA-biomarker programs, please visit View Source

On April 9, 2024 Ferronova reported the initiation of a clinical trial of the company’s FerroTrace nanoparticle technology in patients with gastric and oesophageal cancers (Press release, Ferronova, APR 9, 2024, View Source;Nanoparticle-Trial-Begins-in-Patients-With-Gastric-and-Oesophageal-Cancers [SID1234641961]). It follows the completion of a first-in-human trial in 2020-2022 in oral cancer patients.

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The MAGMAP trial will enrol 60 patients and commenced today with the first patient at the Royal Adelaide Hospital, to be followed by Flinders Medical Centre and Queen Elizabeth Hospital in South Australia, and then expanding to the Peter MacCallum Cancer Centre and Austin Hospital/Olivia Newton John Cancer Centre in Victoria. Trial imaging is supported by the South Australian Health and Medical Research Institute (SAHMRI) and the National Imaging Facility.

The MAGMAP trial (Clinicaltrials.gov ID: NCT05899985) is a multi-centre, partially blinded, side-by-side comparator study to assess the safety and tolerability, feasibility, and potential added diagnostic and clinical value of FerroTrace for mapping high-risk lymph nodes in subjects.

Ferronova Chief Executive Officer Mr Stewart Bartlett said it is potentially an important study offering the promise of an innovative approach for identifying and assessing lymph nodes at high risk of containing cancer.

"Gastric, gastric-oesophageal junction, and oesophageal cancers have very poor outcomes, even where the tumour is localised to a primary location and surrounding lymph nodes where surgery is intended to be curative, and this trial is an important step to test whether our novel technology can improve outcomes in this group of patients."

Studies show following surgery, the 5-year relative survival rates for localised gastric and oesophageal cancers are approximately 74.7% and 48.5% respectively. Where the cancer has also spread to lymph nodes, the 5-year relative survival is only 34.6% and 27.7% [1][2].

Ferronova’s FerroTrace product is a super-paramagnetic iron oxide nanoparticle targeting CD206 receptors found in lymph nodes. It offers a unique targeting mechanism designed to enable a longer lymph node retention time allowing the use of MRI and a handheld surgical magnetic detector to identify and assess lymph nodes containing FerroTrace."

Principal Investigator, Dr Markus Trochsler said the trial will investigate the feasibility of mapping lymph nodes directly draining a primary tumour which theoretically have the highest risk of containing metastasis.

"Gastric and oesophageal cancers are difficult to treat due to unpredictable and extensive lymphatic drainage network in this area of the body, which means lymph nodes containing cancer could potentially be found anywhere from the neck down to the abdomen. At present, when these metastases are very small, they cannot be detected with current imaging technology" Dr Trochsler said.

"This pilot study may lead to providing us with another alternative, being a more informed treatment plan. We are testing whether nanoparticles can identify lymph nodes which are at high-risk of containing cancer cells. It will support us to progress to larger randomised trials where we will investigate tailoring our treatment approach based on the identification and position of these nodes."

Mr Bartlett said the study enrolment is predicted to take 12-15 months, and he hoped the results will lead to new methods of treating patients facing uncertain outcomes.

"The enrolment of the first patient is an important milestone for Ferronova," Mr Bartlett said.

"We are incredibly thankful for the investigators and their support teams, led by Dr Trochsler, as well as Associate Professor Kanhere at the RAH, Professor Watson and Dr Bright at Flinders, Dr Liu at the Austin and Peter Mac, and Dr Dwyer at SAHMRI. They have all put in an incredible amount of work and planning to design and initiate this trial. We look forward to seeing the results when the trial is complete."

On April 9, 2024 Dovetail Genomics reported the debut of its LinkPrep NGS technology, showcasing its potential for de novo detection of structural variants and chromatin topology features in cancer (Press release, Dovetail Genomics, APR 9, 2024, View Source [SID1234641960]). Through its innovative chromatin conformation approach, LinkPrep technology exhibits enhanced sensitivity in detecting translocations and intra-chromosomal rearrangements compared to conventional methods, while also identifying SNVs/InDels within a single assay. Unlike traditional Hi-C methods, LinkPrep technology offers a streamlined process, generating sequenceable libraries from initial samples in a single shift. These findings are being presented at the AACR (Free AACR Whitepaper) Annual Meeting, April 5-10, in San Diego, Calif.

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"Many clinically relevant cancer driver mutations currently go undetected by conventional methods including NGS. Chromatin conformation approaches have a unique capability that will prove to be a powerful solution to address this gap," said Mathew Easterday, Ph.D., J.D., CEO of Cantata Bio. "Because of its high sensitivity, uniform coverage, and rapid workflow, the LinkPrep chemistry is the best solution for detecting these variants. This will improve the discovery and annotation of novel drivers and mechanisms of cancer. Ultimately, this can help optimize treatment decisions and inform the care and management of cancer patients."

LinkPrep technology captures genetic variation within the context of the 3D genome, enabling simultaneous genetic and epigenetic data analyses. As such, it offers a holistic view of genetics, epigenetics, and chromatin conformation revolutionizing our understanding of how gene regulatory networks interact during cancer progression. Furthermore, the novel technology captures chromosome-scale haplotype linkage, enabling applications such as allele-resolved copy number variation, haplotype resolution of variant co-occurrence, and karyotype reconstruction in the context of a cancer genome. LinkPrep technology is fully compatible with off-the-shelf or user-defined hybrid capture panels, offering improved sensitivity over whole genome approaches.

Currently undergoing late-stage validation, Dovetail Genomics is actively seeking strategic partnerships to conduct further studies demonstrating its clinical utility across specific cancer indications.

More detailed information on the LinkPrep technology will be shared in the poster:

Poster Title: LinkPrep: a rapid, high-resolution, proximity ligation method for the detection of structural variants and chromatin topology features in cancer.
Poster Number: LB287 / 3
Location: Section 53, Board 3
Date/Time: April 9th, 9am – 12:30pm
Authors: Cory Padilla, Jonathon Torchia, Daniel Hwang, Mital Bhakta, Lisa Munding

On April 9, 2024 Flare Therapeutics Inc., a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, reported data identifying immunosuppressive cell phenotypes associated with high PPARG expression in urothelial cancer (UC) patients treated with anti-PD1 therapy in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 taking place April 5-10 in San Diego, California (Press release, Flare Therapeutics, APR 9, 2024, View Source [SID1234641959])c.

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"Translational insights from our single cell analysis shed further light on the role that PPARG expression plays in the immune cell phenotypes of advanced UC patients following anti-PD1 therapy," said Michaela Bowden, Ph.D., Chief Development Officer at Flare Therapeutics. "The ongoing study of our lead asset FX-909 – which is currently being evaluated as a monotherapy in a Phase 1 clinical study – includes an exploratory biomarker approach to assess the effect of PPARG inhibition on the innate and adaptive immune response of the patients enrolled, and may inform the ability to expand this novel treatment into a potential combination treatment strategy in the future."

The poster, titled, "PPARG-high circulating monocytes exhibit an immunosuppressive phenotype in urothelial cancer patients treated with anti-PD1," offers a comprehensive analysis of PPARG expression in peripheral blood mononuclear cells (PBMCs) of advanced UC patients. PPARG has been previously associated with immune-mediated resistance and is upregulated in a variety of immune cells such as monocytes, macrophages, and lymphocytes, where it plays a role in their maturation and function.

Flare Therapeutics scientists showed that circulating classical monocytes harboring high levels of PPARG expression exhibited an immunosuppressive phenotype in UC patients who received anti-PD1 therapy. Findings corroborate molecular real-world data presented at the SITC (Free SITC Whitepaper) 2023 Annual Meeting that demonstrated high PPARG expression in patients with muscle-invasive UC is associated with an immunosuppressive tumor microenvironment and shorter real-world progression-free survival to anti-PD1 treatment.

Additional key takeaways from the poster are as follows:

Researchers conducted single-cell RNA sequencing of PBMCs from UC patients treated with anti-PD1 therapy and healthy volunteers – evaluating over 75,000 cells and identifying nine major immune cell populations.
Among peripheral blood cells, the highest PPARG expression was observed within the classical monocyte (CM) population.
PPARG expression in circulating CMs was significantly increased in UC patients compared to healthy volunteers.
PPARG-high circulating classical monocytes in UC patients exhibit a transcriptomic profile associated with immunosuppression and M2 macrophage polarization.

On April 9, 2024 NeoImmuneTech, Inc. (NIT), a global leader in T-cell-based immunotherapy, reported a poster on a pre-clinical study that opens a new field of potential applications for NT-I7 (efineptakin alfa) (Press release, NeoImmuneTech, APR 9, 2024, View Source [SID1234641958]). The poster was presented at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (April 5-10, 2024, San Diego, CA).

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The study explored the efficacy of NT-I7 (efineptakin alfa) in combination with FOLFOX (a combination of 5-fluorouracil, leucovorin, and oxaliplatin), a first-line standard of care (SoC) for colorectal cancer, in an animal model of colorectal cancer (MC38, C57BL/6 mice).

The study’s findings suggest a significant improvement in treatment outcomes when NT-I7 is used alongside FOLFOX, demonstrating a 69% reduction in tumor size compared to the administration of FOLFOX alone. While the overall Absolute Lymphocyte Count (ALC) in the blood was reduced by FOLFOX treatment, the number of anti-cancer specific T cells in the tumor was significantly increased in the combination group compared to FOLFOX alone.

Dr. Luke Oh, President and CEO of NeoImmuneTech said: "We are very excited by results that shows NT-I7 might be effective in combination with cytotoxic chemotherapeutic agents. As chemotherapeutic agents are still the standard of care for most early-stage cancer indications, combining NT-I7 with various chemotherapeutic agents might bring new hope to patients in situations where immuno-oncology is not used."

About Colorectal Cancer
Colorectal cancer is the third most commonly diagnosed cancer and the second most common cause of cancer-related death worldwide. It often begins with growths on the inner lining of the colon or rectum called polyps, which can change into cancer over time. Colorectal cancer affects more than 150,000 people in the US and 1.8 million people worldwide each year. Despite progress in treatment in the last decade, the 5-year survival rate is still only 63% overall and a meager 13% for patients with metastatic disease.

About NT-I7 (efineptakin alfa) (rhIL-7-hyFc)
NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7, and is being developed in oncologic and immunologic indications, where T cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and for sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety profiles, making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.