On September 9, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the introduction of GuardantINFINITY, a next-generation liquid biopsy that provides new, multi-dimensional insights into the complexities of tumor molecular profiles and immune response to advance cancer research and therapy development (Press release, Guardant Health, SEP 9, 2022, View Source [SID1234619332]).

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The new GuardantINFINITY assay provides a more comprehensive molecular profile of tumors than earlier assays, giving researchers access to novel genomic and epigenomic insights to provide a simultaneously deeper and more complete understanding of a tumor’s biology, its system-wide interactions and the associated immune response in a range of applications—from therapy selection to molecular response and longitudinal monitoring. The assay’s extensive methylome panel helps identify the unique, exome-wide methylation pattern that each tumor delivers, providing an important new dimension of research insights that has been largely unexplored in clinical development to date.

"Realizing the promise of precision medicine demands a comprehensive, multi-dimensional understanding of the tumor, the tumor microenvironment and the patient’s immune response," said Helmy Eltoukhy, Guardant Health co-CEO. "GuardantINFINITY, the first product from our new smart liquid biopsy platform, represents a quantum leap forward in the capabilities of liquid biopsies to provide those insights. Drawing on 10 years of research and experience from hundreds of thousands of liquid biopsies, this new assay allows researchers to gain unprecedented insight into a tumor’s molecular underpinnings and its systemic complex interactions to help them accelerate the development of much-needed cancer therapies."

The new platform will enable countless new liquid biopsy applications over time, from deep interrogation of the tumor microenvironment to diverse immuno-oncology applications, much more sensitive therapeutic monitoring, identification of complex prognostic signatures and innate resistance to certain therapies, and more.

GuardantINFINITY is available as a single modular assay with flexible configurations that can be tailored to fit a current application, along with the ability to unlock additional content modules at any time, without incurring the burden or delay of additional sample collection. The core module offers genotyping coverage of more than 800 genes with sample-level methylation detection and tumor fraction score for biomarker discovery, clinical research, therapy selection and response monitoring.

The GuardantINFINITY liquid biopsy is currently available for research use only.

On September Volastra Therapeutics, an oncology company focused on exploiting chromosomal instability (CIN), reported new data from its lead program, a KIF18A inhibitor, validating its therapeutic approach of synthetic lethality to induce tumor cell death (Press release, Volastra Therapeutics, SEP 9, 2022, View Source [SID1234619331]). The data will be presented at the 2022 Consequences of Aneuploidy Conference, organized by the Federation of American Societies for Experimental Biology (FASEB), which takes place September 11 – 16, 2022, in Southbridge, Mass.

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KIF18A is a mitotic kinesin that regulates chromosome alignment during cell division. Leveraging its proprietary CINtech platform, Volastra discovered that CIN-high cancer cells are more dependent on chromosome alignment machinery like KIF18A and are thus more vulnerable to KIF18A inhibition than normal cells.

"Despite the prevalence of chromosomal instability across many tumor types, it has not been fully exploited therapeutically. We are excited to share new preclinical data from our KIF18A inhibitor program showing the ability of this compound to inhibit tumor growth in multiple different models of CIN-high cancer, while leaving normal proliferating cells intact," said Michael Su, Ph.D., Chief Scientific Officer at Volastra. "These findings set our KIF18A inhibitor apart from traditional chemotherapies, which can have a detrimental impact on healthy cells. We anticipate initiating a Phase 1 study for this potential best-in-class KIF18A inhibitor in the second half of 2023."

The FASEB keynote speaker, Professor David Pellman, M.D., of the Dana-Farber Cancer Institute and Volastra Scientific Advisory Board member, states, "The therapeutic potential of targeting chromosomal instability is increasingly compelling. These new data from Volastra’s KIF18A inhibitor further support the promise of developing new and better cancer therapies through a deep understanding of this vulnerability."

Details of Volastra’s oral data presentation at the Consequences of Aneuploidy Conference are as follows:

Title: "Discovery and Development of KIF18A Inhibitors for the Treatment of Chromosomally Unstable Tumors"
Session: Aneuploidy and Tumor Therapy
Date and Time: Tuesday, September 13, 2022; 2:20 p.m. ET
Presenter: Christina Eng, Ph.D., Vice President, Head of Biology, Volastra Therapeutics

About Volastra’s CINtech Platform

Volastra’s CINtech platform harnesses a deep biological understanding of chromosomal instability (CIN) as cancer’s most targetable vulnerability to develop promising therapies for patients. CINtech integrates proprietary imaging technologies, model cell line systems and computational analytics to drive a broad and differentiated pipeline. Volastra recently announced a multi-year, up to $1.1 billion, drug discovery collaboration with Bristol Myers Squibb leveraging Volastra’s proprietary CINtech platform to identify CIN-related targets. In addition, Volastra has a partnership with Microsoft to develop AI technologies for the interrogation of CIN.

On September 9, 2022 Rhizen Pharmaceuticals AG (Rhizen), a Swiss based privately held, clinical-stage biopharmaceutical company reported that it is presenting data from an ongoing Phase 2 trial of Tenalisib in locally advanced or metastatic breast cancer and data from a concluded dose escalation phase of RP12146 at ESMO (Free ESMO Whitepaper) 2022, Paris from Sept 9-13, 2022 (Press release, Rhizen Pharmaceuticals, SEP 9, 2022, View Source [SID1234619330]).

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The multi-centre, randomized phase II study evaluating two doses of Tenalisib, a differentiated PI3K δ/γ inhibitor with additional SIK3 inhibitory activity, has completed 24 weeks of treatment with an impressive Clinical Benefit Rate (CBR) of 57.5% and with no unexpected safety concerns. Treatment with orally dosed Tenalisib was found to be effective in a difficult to treat population where majority of patients had visceral disease and multiple metastatic lesions. In addition, a lone TNBC patient in the trial showed stable disease for more than 6 months and is continuing on the study.

Dose escalation of a Phase -I/Ib trial of RP12146, a next generation PARP 1/2 inhibitor designed to overcome the safety liabilities associated with first generation PARP inhibitors, was successfully completed and is enrolling at the RP2D dose for the expansion phase. RP12146 showed dose related exposures with robust target engagement and notable absence of haematological toxicities viz anaemia and cytopenia. The expansion phase at 400mg BID is currently in progress in genomically qualified ovarian, breast and prostate cancer patients with HRR mutations.

"We are pleased to report the clinical progress of our assets, particularly Tenalisib in a difficult to treat patient population of metastatic breast cancer showing sustained and beneficial disease control. In addition, our carefully designed next generation PARP1/2 inhibitor has successfully demonstrated the safety differential to first generation agents of this class and we are planning to rapidly progress into efficacy evaluations in various solid tumors as mono therapy and as rational combinations," said Swaroop Vakkalanka, Founder & CEO of Rhizen Pharmaceuticals AG.

Tenalisib Poster Presentation schedule:
224P – Efficacy and safety of Tenalisib, a PI3K delta/gamma and SIK3 inhibitor in patients with locally advanced or metastatic breast cancer: Results from a phase II study
Presentation Number: 224P
Speakers: Tamta Makharadze (Tbilisi, Georgia)
Poster Session: Breast cancer, metastatic
Date: Sat, 10.09.2022
Hall 4: Presentation time: (12:00-13:00 CEST)

RP12146 Poster Presentation schedule:
483P – Pre-clinical and early clinical assessment of the safety and anti-tumor activity of RP12146, a PARP1/2 inhibitor in solid tumors
Presentation Number: 483P
Speakers: Piotr Tomczak (Poznan, Poland)
Poster Session: Developmental therapeutics
Date: Mon, 12.09.2022
Hall 4: Presentation time: (12:00-13:00 CEST)

On September 9, 2022 Horizon Therapeutics plc (Nasdaq: HZNP) reported that its Board of Directors authorized the repurchase of up to $500 million of the Company’s ordinary shares (Press release, Horizon Therapeutics, SEP 9, 2022, View Source [SID1234619329]).

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"This share repurchase program reinforces the confidence we have in our strategy and our commitment to deliver long-term value to our shareholders," said Tim Walbert, chairman, president and chief executive officer, Horizon. "Our strong balance sheet and cash generation gives us the flexibility to opportunistically repurchase shares while maintaining ample capital to continue prioritizing business development."

Under the program, the Company may repurchase ordinary shares from time to time on the open market or through privately negotiated transactions or structured repurchase transactions. Open market repurchases may be structured to occur in accordance with the requirements of Rule 10b-18 of the Securities Exchange Act of 1934. The Company may also enter into Rule 10b5-1 plans to facilitate repurchases of its shares under the program. The timing and amount of repurchases will depend on a variety of factors, including the price of the Company’s ordinary shares, alternative investment opportunities, customary restrictions under the Company’s debt agreements, corporate and regulatory requirements and market conditions. The program does not obligate the Company to repurchase any particular amount of its ordinary shares and the program may be modified, suspended or otherwise discontinued at any time without prior notice.

As of June 30, 2022, the Company had cash and cash equivalents of $1.89 billion. The Company expects to fund the repurchase of its ordinary shares under the program with existing cash and cash equivalents.

On September 9, 2022 Novartis reported results from a new pooled exploratory analysis across the entire MONALEESA Phase III program, confirming nearly one year of additional overall survival (OS) benefit in a subgroup of patients with aggressive forms of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer (aBC)1 (Press release, Novartis, SEP 9, 2022, View Source [SID1234619328]). This subgroup analysis found that patients with visceral metastases—including liver metastases and multiple metastatic sites, which are typically associated with a poor prognosis—who were treated with Kisqali (ribociclib) plus endocrine therapy in the first-line setting, achieved a median OS of 62.7 months compared to 52.1 months for those treated with endocrine therapy alone (HR=0.79; 95% CI: 0.65-0.97)1. Data from this analysis will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Paris, France.

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"Patients who have visceral metastases typically have a worse prognosis and often demonstrate resistance to treatment, so as a clinician it is encouraging to see significant survival benefit with ribociclib in the first-line setting in patients with more aggressive disease," said Denise A. Yardley, MD, Senior Investigator, Breast Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, USA. "Ribociclib is the only CDK4/6 inhibitor to show a consistent overall survival benefit in combination with endocrine therapy, while also maintaining quality of life across the Phase III program."

Those with liver metastases on Kisqali plus endocrine therapy in the first-line achieved 44.2 months median OS compared to 38.1 months for those on endocrine therapy alone (HR=0.77; 95% CI: 0.55-1.07). For patients with visceral metastases in three or more organs, first-line
treatment with Kisqali-endocrine therapy achieved 57.7 months median OS compared to 49.3 months for those on endocrine therapy alone (HR=0.81; 95% CI: 0.63-1.03)1.

"The goal for advanced breast cancer treatment is to help people live longer, and we are proud that Kisqali continues to deliver a significant survival benefit while also maintaining quality of life, even for those with harder-to-treat disease," said Jeff Legos, Executive Vice President, Global Head of Oncology and Hematology at Novartis. "We are committed to demonstrating what makes Kisqali a unique CDK4/6 inhibitor, thus providing patients and oncologists confidence in this therapeutic option."

HARMONIA head-to-head CDK4/6 inhibitor trial design
Also at ESMO (Free ESMO Whitepaper), the trial design will be presented for HARMONIA, the first prospective, head-to-head Phase III trial of CDK4/6 inhibitors being conducted in collaboration with SOLTI Innovative Cancer Research, to evaluate Kisqali vs. Ibrance* (palbociclib) for patients with advanced HR+/HER2-, HER2-enriched subtype, ultimately exploring what makes Kisqali unique at a molecular level13. HARMONIA seeks to test if Kisqali improves the course of HR+/HER2- aBC by changing tumor biology to enable a better response to endocrine therapy as compared to Ibrance*, and could further substantiate differences seen among these CDK4/6 inhibitors. HER2-enriched is an intrinsic subtype associated with a very poor prognosis and endocrine-resistance, as compared to luminal disease. The global, multicenter, randomized, open-label, Phase III study has a primary outcome of progression-free survival (PFS), and secondary outcomes include OS and PFS2. HARMONIA is currently ongoing with an anticipated enrollment of 456 patients.

About Kisqali (ribociclib)
Kisqali is the only CDK4/6 inhibitor with proven overall survival benefit across all its three pivotal Phase III advanced breast cancer trials2-12, and is recognized by the National Comprehensive Cancer Network (NCCN) guidelines as the only CDK4/6 inhibitor with overall survival benefit in first-line HR+/HER2- advanced breast cancer14. Additionally, Kisqali has the highest rating of any CDK4/6 inhibitor on the ESMO (Free ESMO Whitepaper) Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line premenopausal patients with HR+/HER2- advanced breast cancer15. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6i, received a score of four out of five for postmenopausal patients with HR+/HER2- advanced breast cancer treated in the first line16.

Kisqali has been approved in more than 95 countries worldwide, including by the United States Food and Drug Administration (FDA) and the European Commission, for the treatment of women with HR+/HER2- advanced or metastatic breast cancer in combination either with an aromatase inhibitor or with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy13,17. Kisqali in combination with fulvestrant is approved as initial endocrine-based therapy or following disease progression on endocrine therapy in men by the FDA17.

Novartis is committed to continuing to study Kisqali in breast cancer. NATALEE is a large Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO)18. Additionally, Novartis is collaborating with the Akershus University Hospital in Norway on the NEOLETRIB trial, a neoadjuvant Phase II trial studying the effects of Kisqali in HR+/HER2- early breast cancer and to discover the potentially unique underlying mechanism of action19.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

Please see full Prescribing Information for Kisqali, available at www.Kisqali.com.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with metastatic breast cancer.