On May 31, 2022 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported the launch of the Twist Human Methylome Panel, a product now available to customers that can advance applications in cancer metastasis, human development and functional genetics (Press release, Twist Bioscience, MAY 31, 2022, View Source [SID1234615279]). The panel can be used to identify a robust, collated set of CpG sites, methylated cytosine and guanine nucleic bases, across the human genome to identify biologically relevant methylation markers. Compared to traditional array based or whole genome bisulfite sequencing approaches, this panel provides overall cost savings while also covering previously unknown methylation markers. The Twist Human Methylome Panel can also be used as a first pass discovery tool to identify methylation biomarkers that can then be used in a variety of applications, such as more targeted liquid biopsy panels.

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The DNA methylome is the comprehensive set of nucleotides within the genome that have a methyl group attached. DNA methylation plays a key role in many biological processes, including cancer. When present on a single nucleotide, a methyl group can alter genetic behavior without changing the DNA sequence. Analyzing the pattern in which methylation occurs within a specific genetic sequence as well as the fraction of the genome that has a methyl group attached (methylated) provides a unique understanding of disease pathology. CpG sites, which often repeat to create CpG islands, turn a gene "on" or "off" and are associated with neurodegeneration, cancer and multiple rare diseases. Detection of CpG islands therefore can inform diagnoses or development stage of multiple diseases.

The Twist Human Methylome Panel is highly targeted to capture and detect the most recently identified and relevant CpG methylation regions in the genome. Twist uses hybrid capture panels to explore the methylome and the content that can be investigated to include 84.2% of CpG islands as well as other CpG sites.

"With the customizable Twist Human Methylome Panel, we are able to cover four times the amount of CpG sites compared to average microarrays. Using our NGS-based panel provides a higher dynamic range, allowing more accurate identification of differentially methylated regions, which we believe will enhance research-based assays and diagnostic tests that incorporate this dynamic tool," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "Previously, when identifying methylation markers, researchers had to choose between a low-cost, static option or a very expensive panel that covers a significant portion of the methylome, but often more than needed. As technology progresses, the compromise that researchers need to make between cost and coverage becomes less and less."

"We look forward to expanding our work with Twist as well as extending our epigenomics expertise and offerings to customers by incorporating the Twist Human Methylome Panel into our Epigenomics Profiling Services. This aligns with our efforts to continue offering new solutions to link methylation research with a wide range of disease indications and progression," said Didier Allaer, CEO of Diagenode, a leading epigenomics company and early access customer for the Twist Human Methylome Panel. "The new panel will enable us to offer a solution with broad coverage of the human methylome and to bring epigenetics research to new frontiers of biomarker discovery on clinical samples."

About Twist Human Methylome Panel

The Twist Human Methylome Panel enables the identification and study of methylation biomarkers spanning a wide range of targets and applications. The 123 megabase panel covers 84.2% of CpG island sites contained within the human genome and is optimized with the Twist Methylation workflow for robust end-to-end performance. The high capture efficiency increases the sensitivity of detection and internal data show that the Twist Human Methylome Panel achieves a depth of coverage of 90% of bases at 30x coverage with high probe specificities of 95% on-target rates, as well as high uniformity across the target region.

On May 31, 2022 Greenfire Bio, LLC reported that its subsidiary, Green3Bio, and its collaborators at MD Anderson Cancer Center will present an update on the ongoing first-in-human clinical trial of GRN-300 at the upcoming ASCO (Free ASCO Whitepaper) 2022 Annual Meeting (Press release, Greenfire, MAY 31, 2022, View Source [SID1234615297]). GRN-300 is a first-in-class, orally bioavailable novel small molecule inhibitor of the Salt Inducible Kinases 2 and 3 (SIK2/SIK3) that is highly expressed in ovarian cancer and has been identified to play a pivotal role in several other cancers. The transition of this emerging biologic pathway and a novel agent into the clinic marks a successful step in the progress of the GRN-300 program. The goal of the clinical study is to determine the recommended Phase 2 Dose (RP2D), safety/tolerability and the tumor response of GRN-300 as a monotherapy or in combination with paclitaxel in subjects with ovarian cancer.

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This study is registered at ClinicalTrials.gov Identifier: NCT04711161.
Format: Poster Presentation
Abstract number: TPS5616
Session: Poster Session/Gynecologic Cancer
Time: Saturday, June 4, 2022, 1:15 PM-4:15 PM CDT
Presenter: Siqing Fu, PhD, MD (Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center)

Title: GRN300–001: Phase 1/1b evaluation of the safety, pharmacokinetics and efficacy of GRN-300, a salt-inducible kinase inhibitor, alone and in combination with paclitaxel, in recurrent ovarian, primary peritoneal, and fallopian tube cancers

About Ovarian Cancer
According to the American Cancer Society, ovarian cancer ranks fifth in cancer deaths among women. They estimate that in 2022 there will be about 19,880 new cases of ovarian cancer diagnosed in the United States and that about 12,810 will die of the disease. According to the World Cancer Research Fund International, there were about 313,000 new cases of ovarian cancer diagnosed worldwide in 2020. Ovarian cancer is difficult to detect at an early, more treatable stage; therefore, the current lack of salvage treatment for women, who experience a recurrence, results in a 5-year survival rate of less than 30%.

About GRN-300
GRN-300 (previously ARN3261) is an orally bioavailable first-in-class novel, small molecule, dual inhibitor of the salt-inducible kinases 2 and 3 (SIK2, SIK3). This agent has the potential to overcome chemoresistance based on its mechanism of action (MOA) and synergistic effects with standard of care including chemotherapy, PARP inhibitors, and immune checkpoint inhibitors (ICIs). SIK2 is overexpressed in 30% of ovarian cancer specimens suggesting a multifunctional role of SIK2/3 in tumorigenesis. SIK2 and SIK3 are known to play an oncogenic role in other tumor types, including prostate cancer, breast cancer, diffuse large B-cell lymphoma, and melanoma. Higher levels of expression of SIK2 have been shown to be significantly correlated with poor progression-free survival in patients with high-grade serous ovarian cancers. GRN-300 attenuated tumor growth in several preclinical xenograft ovarian cancer models as a single agent and in combination with paclitaxel. The compound completed the first dose escalation groups without DLT, and preliminary PK analysis indicate dose proportionality.

On May 31, 2022 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that it it will present a poster on the 4-1BB conditional agonist antibody ATOR-1017 at the 2022 ASCO (Free ASCO Whitepaper) (American Society of Clinical Oncology) Annual Meeting, being held in Chicago June 3-7 (Press release, Alligator Bioscience, MAY 31, 2022, View Source [SID1234615246]).

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The poster, entitled "Initial findings from a first-in-human, multicenter, open-label study of ATOR-1017, a 4-1BB antibody, in patients with advanced solid malignancies", outlines results from Alligator’s first-in-human clinical trial with ATOR-1017, which is being developed as a tumor-directed therapy for advanced/metastatic solid cancers.

The results, to be presented at ASCO (Free ASCO Whitepaper), demonstrate an excellent safety profile. Five (22.7%) of the 22 patients treated with ATOR-1017 experienced grade 3-4 treatment-related adverse events (TRAEs). None of the TRAEs resulted in treatment discontinuation. No dose-limiting toxicity was observed, and thus the maximum tolerated dose (MTD) of ATOR-1017 has not been reached. ATOR-1017 exhibits a dose dependent and favorable pharmacokinetic profile. Activation of peripheral T cells and increased levels of soluble 4-1BB was observed across active dose levels of ATOR-1017, demonstrating biological activity and proof of mechanism.

Stable disease was achieved as best objective response in 10 (45%) of patients, with the longest treatment duration being 16 months.

Overall, the data showed that ATOR-1017 is safe and well-tolerated at doses up to 600 mg and has shown signs of clinical benefit. Dose escalation continues at the 900 mg dose and data from this cohort is expected to be reported in 2022.

"We are excited to be able to present these very promising data at ASCO (Free ASCO Whitepaper), outlining the strong safety profile and signs of efficacy of our ATOR-1017 drug candidate," said Søren Bregenholt, PhD, CEO of Alligator Bioscience. "4-1BB antibodies have been plagued with poor efficacy or unacceptable safety profile, but ATOR-1017 is distinct from other 4-1BB antibodies, partly because of its unique binding profile but also because its immunostimulating function is dependent on cross-linking to Fc-gamma receptors on immune cells. This localizes the immunostimulation to the tumor region, where both 4-1BB and Fc-gamma receptors are expressed at high levels. This means that ATOR-1017 has the potential to address a significant unmet medical need, and we look forward to finalizing this study and selecting a recommended dose for the upcoming Phase 2 study."

The Phase I study with ATOR-1017 is an open-label, dose-escalation study in patients with histologically confirmed, advanced, and/or refractory solid cancer (NCT04144842). The primary objective of the study is to investigate the safety and tolerability of ATOR-1017 and to determine the recommended dose for subsequent Phase 2 studies.

On May 31, 2022 M2GEN reported that continues to partner with our Oncology Research Information Exchange Network (ORIEN) members to enable breakthrough scientific research that advances patient care (Press release, M2Gen, MAY 31, 2022, View Source [SID1234615263]). ORIEN researchers are showcasing several projects at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting that utilize M2GEN’s rich longitudinal clinico-genomic Avatar data, and feature collaborations with scientists across ORIEN and M2GEN. These projects highlight research discoveries across four key areas: gastrointestinal cancers, developmental therapeutics, immunotherapy, and gynecologic cancers.

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Learn more about how ORIEN investigators are collaborating with fellow Network members and M2GEN to leverage the expansive clinical and molecular Avatar database, for the research being featured at ASCO (Free ASCO Whitepaper) 2022:

On Saturday, June 4, during ASCO (Free ASCO Whitepaper)’s Gastrointestinal Cancer— Gastroesophageal, Pancreatic, and Hepatobiliary poster session:

Gudbjorg Jonsdottir, M.D., of the University of Iowa Holden Comprehensive Cancer Center will present a poster entitled "The impact of HRD in patients with pancreatic adenocarcinoma who undergo surgical resection: an updated analysis" (Abstract: 4132, Poster: 118, Full Text).
Summary: Utilizing data from 311 pancreatic cancer patients in the ORIEN Avatar database, Dr. Jonsdottir determined that patients with one of 18 genetic mutations in the homologous recombination repair (HRR) pathway, which is involved with repairing DNA, had improved survival if treated with platinum-based chemotherapy compared to those who were not.
On Sunday, June 5, during ASCO (Free ASCO Whitepaper)’s Developmental Therapeutics—Immunotherapy poster session:

Ahmad Tarhini, M.D., Ph.D., of the H. Lee Moffitt Cancer Center & Research Institute will present a poster entitled "Predictors of immunotherapeutic benefits in patients with advanced malignancies treated with immune checkpoint inhibitors utilizing "real-world" data" (Abstract: 2618, Poster: 273, Full Text)
Summary: Of 1,214 patients with 27 cancer types in the ORIEN Avatar database treated with immune checkpoint inhibitor (ICI) therapies, Dr. Tarhini found that there was a significant increase in overall survival if the ICI was given as the first treatment. Furthermore, for patients with melanoma, Dr. Tarhini identified six patterns of gene expression that correlated significantly with improved survival on ICIs.

Payman Ghasemi Saghand, Ph.D., of the H. Lee Moffitt Cancer Center & Research Institute will present a poster entitled "A deep learning approach utilizing clinical and molecular data for identifying prognostic biomarkers in patients treated with immune checkpoint inhibitors: An ORIEN pan-cancer study" (Abstract: 2619, Poster: 274, Full Text)
Summary: Utilizing ORIEN Avatar data for 522 cancer patients treated with immune checkpoint inhibitor (ICI) therapy, Dr. Saghand developed a machine learning algorithm correlating survival outcomes to specific gene expression patterns. The algorithm aims to predict the genes that are associated with resistance to ICI therapy; future work will determine the mechanism behind this genetic resistance.

Kevin Chua, M.D., of the Rutgers Cancer Institute of New Jersey will present a poster entitled "Comparing Rate of Immunotherapy Treatment Change Due to Toxicity by Gender" (Abstract: 2656, Poster: 310, Full Text)
Summary: Utilizing clinico-genomic data from 447 patients treated with immunotherapies in the ORIEN Avatar database, Dr. Chua analyzed differences between treatment courses in female and male patients. He found that female patients were on immunotherapies for a shorter overall period, but there was no difference in treatment discontinuation rates due to adverse side effects.
On Sunday, June 5, during ASCO (Free ASCO Whitepaper)’s Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology poster session:

Daniel Spakowicz, Ph.D., of The Ohio State University will present a poster entitled "Pan-cancer analysis of exogenous (Microbial) sequences in tumor transcriptome data from the ORIEN consortium and their association with cancer and tumor microenvironment" (Abstract: 3113, Poster: 105, Full Text)
Summary: Utilizing RNA-sequencing data, Dr. Spakowicz analyzed the microbiomes of 2,892 tumors collected from patients in the ORIEN Avatar database and 2,720 patient samples in The Cancer Genome Atlas. The tumor microbiome was found to correlate better with the type of cancer than the level of oxygen in the tumor microenvironment, suggesting that the tumor microbiome is dependent on location.

Emily Hoskins of The Ohio State University will present a poster entitled "Pan-cancer landscape of PD-L1 and PD-L2 structural variations" (Abstract: 3133, Poster: 125, Full Text)
Summary: PD-L1 and PD-L2 are proteins that are involved in suppressing the creation of new immune cells; cancer cells often produce increased amounts of these proteins to evade the immune system’s attack. Utilizing large datasets, including ORIEN Avatar whole-exome data, Emily Hoskins curated 514 cancer cases with structural variations in PD-L1 and PD-L2 that increased expression of these genes. Patients with these gene rearrangements may potentially respond better to therapies that block PD-L1 or PD-L2 activity.
Additionally, in the Gynecologic Cancer section of the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting Proceedings, a supplement to the Journal of Clinical Oncology:

McKayla Riggs, M.D., of the University of Kansas Markey Cancer Center will publish an abstract entitled "DACH1 mutation frequency in endometrial cancer is associated with high tumor mutation burden in a nationwide cohort" (Abstract: e17634, Full Text)
Summary: From 691 endometrial cancer patients in the ORIEN Avatar database, Dr. Riggs found that those with mutations in DACH1 had overall tumor mutation burden and co-occurred with other genome destabilizing mutations. The researchers also found that DACH1 mutations were more prevalent in the local Appalachian region than elsewhere in the country. Their findings suggest DACH1 may be a candidate biomarker for future immunotherapy trials, particularly for endometrial cancers.
To inquire about partnering with M2GEN and the Oncology Research Information Exchange Network (ORIEN), or our rich longitudinal clinico-genomic ORIEN Avatar dataset, contact [email protected].

On May 31, 2022 Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s investigational new drug (IND) application for its lead product candidate, JANX007, a PSMA-TRACTr in development for the treatment of metastatic castration-resistant prostate cancer (mCRPC) (Press release, Janux Therapeutics, MAY 31, 2022, View Source [SID1234615280]). JANX007 is the Company’s lead novel T cell engager (TCE) therapeutic from its TRACTr platform. Janux plans to initiate a Phase 1 clinical trial for JANX007 in the second half of 2022.

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"We are proud to announce today the clearance of Janux’s first IND – a critical milestone for our TRACTr platform and for the Company as we advance a broad pipeline of next generation immunotherapies to address unmet needs and improve the treatment of cancer," said David Campbell, Ph.D., President and CEO of Janux. "JANX007 is uniquely designed to overcome the clinical limitations of existing TCE approaches, potentially providing mCRPC patients a safer therapeutic option, while also generating potent anti-tumor activity by enabling the delivery of a higher concentration of active drug. With this IND acceptance, we are on track to advance JANX007 into the clinic in the second half of this year."

Unlike existing TCE approaches to prostate cancer that have been limited to-date by dose-limiting toxicities, poor pharmacokinetic (PK) profiles and attenuated efficacy, JANX007 is designed as a safer, highly potent anti-tumor approach to mCRPC. In preclinical studies, JANX007 was well tolerated in non-human primates with limited healthy tissue toxicities and cytokine release syndrome and exhibited enhanced safety and PK properties relative to unmasked TCEs. These data along with the superior manufacturability properties of JANX007 support its further development as an attractive mCRPC therapeutic.