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Twist Bioscience Launches Circulating Tumor DNA Reference Controls for Development of Liquid Biopsy Assays

On December 7, 2021 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of synthetic DNA using its silicon platform, reported the launch of the Twist cfDNA Pan-cancer Reference Standards, a high-quality standardized control for use in the development and continuous monitoring of liquid biopsy tests to detect cancer from blood samples (Press release, Twist Bioscience, DEC 7, 2021, View Source [SID1234596571]).

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Liquid biopsy tests, which rely on NGS-based circulating tumor DNA (ctDNA) analysis, are a promising and growing area in clinical oncology. Liquid biopsy assays can accurately identify a single tumor variant in the presence of thousands of healthy cells. The most sought-after applications in the ctDNA field include early detection of disease, personalization of therapy, monitoring response to therapy, and monitoring for relapse of disease. Developing and standardizing these ultra-sensitive yet accurate ctDNA-based assays is paramount to ensure the resulting analysis from the test informs clinical decisions reliably.

"As the number of clinical validations of liquid biopsies increase, a true ctDNA pan-cancer reference standard, beyond the few variants that are widely available today, will increase liquid biopsies’ accuracy in detecting specific oncogenes and variants," said Florian Battke, director of development at CeGaT GmbH. "There is an obvious benefit of using a synthetic approach like the Twist ctDNA standards, as they are very high quality and closely mimic the properties of real samples without the instability."

The Twist cfDNA Pan-cancer Reference Standards material consists of synthetically designed variant sequences that mimic ctDNA combined with background DNA that is derived from, and closely mimics, human-derived cell-free DNA (cfDNA).

This reference standard can be used by researchers to assist in the development of liquid biopsy assays to establish the analytical limit of detection (LoD) for specific cancer variants and as a control to track the quality of an NGS assay workflow to ensure the fidelity of the assay process.

The Twist cfDNA Pan-cancer Reference Standards can be used within the liquid biopsy workflow, which includes Twist Library Preparation Kit and the Twist Mechanical Fragmentation Kit, for maximum efficacy and provides a large and diverse number of clinically relevant variants, combining best in class methods for variant synthesis with unrivaled control over the specific target allele frequencies in a format which closely mimics the size distribution and fragmentation profile of cfDNA. In contrast, traditional reference standards are limited in the number and variation of variants and typically use cell line-derived DNA which can carry unwanted sequence variations and variable fragment length.

Emily Leproust, CEO and co-founder of Twist Bioscience said, "Building on the success of our SARS-CoV-2 positive controls that are now used in COVID-19 tests worldwide, we believe having precise standard cancer reference controls that can be used in a validated workflow will be a gamechanger to confirm clinical insights from genetic information. While it is possible to create cell-based controls specific to each test, using a robust, precise control set that detects variation in test assays will be pivotal in both development and ongoing monitoring of a wide variety of liquid biopsy assays."

Applying the right reference materials is essential to benchmark the complexity and biological content of DNA found in liquid biopsy samples for assay development and validation. The Twist ctDNA reference material contains over 400 variants, including SNVs, indels, fusions and structural variants, as well as more than 140 clinically relevant variants. All variants are offered with a unique tiling design, which accurately mimics the pattern of naturally derived ctDNAs. All of these features make the Twist ctDNA reference a high-quality standard for the ctDNA variants that cancer liquid biopsy assays are designed to detect.

To demonstrate the limit of detection (LoD) of an ultra sensitive NGS-based liquid biopsy assay, using an accurately quantified ctDNA control is key. Twist’s silicon platform provides an advantage by specifically writing individual variants of interests, thus preventing any interference caused by contaminants derived from cell culture-based methods. Twist’s ctDNA reference material is also well-characterized and quantified, using industry-standard and proprietary methods (NGS, ddPCR, and fluorescence-based quantification).

Xcovery Acquires Majority Controlling Stake in Meryx Pharmaceuticals

On December 7, 2021 Xcovery Holdings, Inc., an oncology focused bio-pharmaceutical company, reported the acquisition of a majority and controlling stake in Meryx Inc., a clinical stage immuno-oncology company based in Chapel Hill, North Carolina developing TKIs in a range of hematologic and solid malignancies, including lung cancer (Press release, Xcovery, DEC 7, 2021, View Source [SID1234596570]). The partnership and synergies between Xcovery and Meryx will accelerate and enhance both Xcovery’s and Meryx’s missions to develop small molecule oncology drugs for patients all over the world. A new leadership and board of directors reflecting the new ownership will be established in the coming weeks.

"We are thrilled to partner on a global level with Meryx, a firm with whom we already have an out-licensing collaboration in China," said Lieming Ding, M.D., Chairman of the Xcovery Board and Chairman of Betta Pharmaceuticals, a major Chinese pharma company. "Meryx has done a remarkable job of developing an innovative cutting-edge oncology pipeline. We are looking forward to building on this impressive track record and collaborating closely with its team to advance the clinical trials of these promising drug candidates."

"Xcovery is at a very exciting juncture in its history," stated Dr. Giovanni Selvaggi, Xcovery’s CEO and CMO. "We are well positioned to accelerate and further strengthen all Meryx’s ongoing R&D projects, both at clinical and pre-clinical level. Jointly with Meryx, and with the support of Betta, we are building a global company to benefit cancer patients worldwide through innovation and precision," added Dr Selvaggi.

Dr. Stephen Frye, Meryx’s CEO also stated, "Through the new collaboration with Xcovery and with our longstanding collaboration with Betta, Meryx will have the opportunity to advance our exciting clinical-stage and preclinical pipeline at a faster pace to improve cancer patients’ care."

Details of the transaction have not been disclosed.

Takeda Unveils New Research to Advance Patient Care in Hematology and Oncology at 63rd American Society of Hematology (ASH) Annual Meeting

On December 7, 2021 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that it will present a total of 23 company-sponsored abstracts at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 11-14, 2021 in Atlanta, Georgia (Press release, Takeda, DEC 7, 2021, View Source [SID1234596569]). Takeda’s latest research in hematologic diseases focuses on optimizing patient care, while advancing novel approaches for patients with limited or ineffective treatment options.

Takeda Oncology will present data in multiple myeloma, lymphoma and leukemia from the company’s marketed products as well as provide early insights into the potential of therapies leveraging the innate immune system. In hematology, Takeda will present prospective, post-hoc and real-world data across a range of hematological disorders, aimed at addressing the breadth of needs within the bleeding disorders community, while investigating potentially transformative treatment options.

"At Takeda Oncology, improving patient care is the foundation for all we do," said Christopher Arendt, Ph.D., Head of Oncology Cell Therapy and Therapeutic Area Unit of Takeda. "At this year’s ASH (Free ASH Whitepaper), we look forward to showcasing our deep legacy and leadership in the treatment of hematologic cancers by sharing data that will help to inform the optimal use of our established medicines and presenting research from two pipeline programs designed with the potential to drive potent and effective immune attacks against cancer. While early-stage, we continue to explore these new treatment pathways as we seek to outsmart cancer."

"The hematological data we are highlighting at ASH (Free ASH Whitepaper) this year demonstrates our commitment to furthering personalized care strategies, and leading scientific innovation to address unmet needs within the global bleeding disorders community," added Neil Inhaber, Head of Global Medical Affairs, Rare Genetics and Hematology. "In addition to developing our promising pipeline of investigative molecules, which may have transformative potential for multiple rare and life-threatening hematological conditions, we remain focused on expanding the use of our current portfolio to benefit more people living with rare bleeding disorders."

A full list of company-sponsored abstracts can be found here.

rADAMTS13 (TAK-755), modakafusp alfa (TAK-573), and subasumstat (TAK-981) are investigational compounds that have not been approved for use by the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), or any other regulatory authorities.

Takeda’s Commitment to Oncology

Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.

Takeda’s Commitment to Hematology

Takeda is a leader in hemophilia with the longest heritage and market-leading portfolio, backed by established safety and efficacy profiles with decades of real-world experience. We have 70+ years driving innovation for patients and a broad portfolio of 11 products across multiple bleeding disorders. Our experience as a leader in hematology means we are well prepared to meet today’s needs as we pursue future developments in the care of blood disorders. Together with the hematology community, we are raising expectations for the future, including earlier diagnosis, earlier and full protection against bleeds, and more personalized patient care.

Immunome to Participate in Fireside Chat Hosted by Cantor Fitzgerald

On December 7, 2021 Immunome, Inc. (Nasdaq: IMNM), a biopharmaceutical company that utilizes its human memory B cell platform to discover and develop first-in-class antibody therapeutics, reported that members of management will participate in a fireside chat hosted by Cantor Fitzgerald Analyst Brian Cheng on Wednesday, December 8, 2021 at 1:00 p.m. ET (Press release, Immunome, DEC 7, 2021, View Source [SID1234596567]).

The live call is reserved for institutional clients of Cantor Fitzgerald. A replay of the webcast can be accessed from the Investor Relations section of the company’s website at www.immunome.com. The webcast replay will be available at the conclusion of the live presentation for approximately 30 days.

SynDevRx Announces Research Collaboration with Queensland University of Technology (QUT) to Study the Effects of SDX-7320 In Advanced Prostate Cancer Models

On December 7, 2021 SynDevRx, Inc., a clinical-stage biotechnology company leading the development in treatments for obesity-accelerated cancers, reported a research collaboration with Australia’s Queensland University of Technology (Press release, SynDevRx, DEC 7, 2021, View Source [SID1234596566]). The collaboration with Professor Colleen Nelson, PhD, and her team will study the role of methionine aminopeptidase 2 (MetAP2) inhibition in tumor growth in castration resistant and other treatment resistant forms of prostate cancer.

Obesity and systemic metabolic dysfunction like pre-diabetes and type 2 diabetes are known to make many solid tumors more aggressive, including prostate cancer. MetAP2 inhibitors, such as evexomostat (SDX-7320), have been clinically shown to improve systemic metabolic hormone dysregulation1 and to possess direct anti-tumor, anti-metastatic and anti-angiogenic properties2. This combination of attributes may be well suited to sever the link between metabolic dysfunction and cancer, and may prove to be effective in treating advanced prostate cancer in combination with standard-of-care therapies.

Professor Nelson is the founder and executive director of the Australian Prostate Cancer Research Centre – Queensland (APCRC-Q) and Chair of Prostate Cancer Research at Queensland University of Technology (QUT). APCRC-Q, is one of the leading global research facilities investigating the connection between prostate cancer and dysregulated metabolic hormones and pathways, and how these affect prostate cancer progression and metastasis. "The downstream effects of obesity change the tumor microenvironment in ways highly favorable to prostate cancer recurrence, progression and metastasis. Hyperleptinemia and hyperinsulinemia are well-established, negative side effects of androgen deprivation therapy (ADT) and other treatments that block the androgen axis in prostate cancer. The APCRC-Q has been investigating this relationship using targeted drugs in preclinical models that inhibit metabolic pathways induced by ADT, through tumor promoting pathways activated systemically, and through direct tumor cell adaptation," said Colleen Nelson, PhD, lead investigator. "We’re very excited to study SynDevRx’s SDX-7320 inhibition of MetAP2 in our well-vetted models of treatment resistant advanced prostate cancer models."

The APCRC-Q team’s research focuses on pathways activated by ADT, including alterations in metabolism that are druggable with novel targeted agents. They recently showed that pharmacological blockade of leptin receptor or the activation of adiponectin signaling was efficacious in significantly reducing tumor burden and in delaying progression to castration resistance in animal models. The APCRC-Q team has also been targeting metabolic pathways directly through mitochondrial activity or lipid synthesis in models of CRCP and ENZ resistance.

"Professor Nelson team’s work has clearly demonstrated the central role that leptin and adiponectin play in the feedback loop of androgen deprivation and results in the emergence of treatment resistance," said Peter Cornelius, PhD, senior director of translational research at SynDevRx. "Her lab has some of the best models for studying the deleterious effects of inhibition of the androgen receptor axis in prostate cancer, identifying mechanisms of resistance and then targeting those proteins driving the resistance in pre-clinical prostate cancer models. Given our clinical results showing evexomostat (SDX-7320) significantly lowers leptin and increases adiponectin in late-stage cancer patients, we’re thrilled to work with Professor Nelson and her expert team on testing the potential beneficial effects that SDX-7320/MetAP2 inhibition could play in these validated models."

"SynDevRx is establishing global collaborations with leading research institutions focused on the downstream effects that obesity and dysregulated metabolic hormones have on cancer progression and metastasis. We invite other researchers to work with us as we untangle these complex and critical interactions between cancer and dysregulated metabolic hormones," said SynDevRx’s co-founder and Chief Business Officer James Shanahan.

(Proietto et al., Diabetologia 2018 Sep;61(9):1918-1922)
(Mann-Steinberg et al., "TNP-470: The Resurrection of the First Synthetic Angiogenesis Inhibitor." (2008).)
About SDX-7320

SynDevRx believes that evexomostat (SDX-7320) is the first drug being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or HbA1c, pre-diabetes or insulin/leptin resistance. For certain tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadlier. Evexomostat acts by binding irreversibly to its target enzyme MetAP2, triggering downstream improvements in the metabolic hormones insulin, leptin and adiponectin, improvements in key lipids, and inhibition of the important angiogenic proteins bFGF and VEGF-C, as was demonstrated in a Phase 1 clinical study in late-stage cancer patients. In preclinical studies, evexomostat also directly inhibited multiple cell cycle signaling pathways, provided synergistic anti-tumor effects in combination with a PI3K inhibitor, reduced angiogenesis, controlled aberrant metabolic hormone signaling, and reversed obesity-induced immune suppression within the tumor micro-environment of tumor-bearing obese mice. Evexomostat (SDX-7320) is being developed for use in combination with clinically indicated standard-of-care cancer therapies for breast and prostate cancers.