On May 30, 2024 QIAGEN (NYSE: QGEN; Frankfurt Prime Standard: QIA) and Myriad Genetics (NASDAQ: MYGN) reported they will develop a globally distributable kit-based test for analyzing Homologous Recombination Deficiency (HRD) status (Press release, Qiagen, MAY 30, 2024, View Source [SID1234643866]). This next-generation sequencing (NGS) test aims to support research into personalized medicine in multiple solid tumor types, including ovarian cancer and is expected to enhance decentralized testing capacities once a regulated product is developed with pharmaceutical partners. The project builds on the recently announced master collaboration agreement between the two companies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The test will be based on QIAGEN’s QIAseq xHYB technology, QIAGEN Digital Insight solutions, which creates a sample to insight HRD solutions, and Myriad’s proprietary FDA-approved MyChoice CDx, a single-site PMA-approved centralized testing service for analyzing HRD in certain tumors. MyChoice CDx assesses the HRD status by examining a tumor’s DNA repair capabilities, particularly focusing on BRCA1 and BRCA2 gene mutations and calculating a Genome Instability Score (GIS). The GIS aids in pinpointing ovarian cancer patients who are most likely to benefit from targeted treatments, such as LYNPARZA (olaparib) by AstraZeneca.

"Our partnership with Myriad Genetics underscores a shared commitment to advancing cancer diagnostics. Together, we aim to broaden the accessibility of HRD tests, allowing an increasing number of cancer patients to benefit from tailored treatments," said Fernando Beils, Senior Vice President and head of the Molecular Diagnostics Business Area. "By introducing a distributable HRD test, we anticipate a reduction in the time required for therapy decisions, a decrease in associated costs, and shorter turnaround times compared to outsourced testing, ultimately benefitting the patients."

The MyChoice CDx assay can identify 34% more tumors with HRD using the GIS score compared to other methods only using percent loss of heterozygosity (%LOH)[1]. Given that approximately 48% of ovarian cancer tumors exhibit HRD[2], often due to specific mutations within the tumor, expanding access to this assay is vital for advancing personalized medicine and ensuring that patients receive the most appropriate treatments.

We’re excited to share this milestone in our partnership with QIAGEN as we work collectively to advance cancer care worldwide," said Patrick Burke, Executive Vice President of Strategy and Innovation, Myriad Genetics. "By extending the global reach and ease of access to Myriad’s gold-standard HRD-testing technology we aim to help drive wide-spread and broader clinical adoption of HRD testing. This milestone demonstrates what the QIAGEN and Myriad partnership is uniquely able to deliver to pharmaceutical partners – propriety content, cutting edge assay platforms, clinical trial execution, and world-wide CDx product distribution."

QIAGEN will manage the development and distribution of the kit-based HRD test outside of the United States. The IP license grants QIAGEN the capability to collaborate with pharmaceutical partners to create an IVD-validated test, intended for use as a companion diagnostic outside of the United States. The combined regulatory expertise of QIAGEN and Myriad enables seamless compliance and integration in clinical and companion diagnostic applications.

QIAGEN’s QIAseq panels enable efficient and accurate NGS library preparation. Over 4 million samples have been processed with QIAseq panels for cancer testing applications.[3]

QIAGEN has master collaboration agreements to develop and commercialize companion diagnostics with more than 30 global pharma and biotech companies – a deep pipeline that helps advance precision medicine in diverse disease indications, tailoring a patient’s treatment to the genetic profile identified by companion diagnostics testing. Myriad has provided testing support for hundreds of clinical trials, has obtained 10 companion diagnostic approvals from the FDA and PMDA, and anticipates that the QIAGEN partnership will drive the expansion of the Myriad’s oncology products portfolio.

On May 30, 2024 Precision Biologics, Inc. reported that novel findings from its ongoing phase 2 clinical trial, combining NEO-201 with pembrolizumab for the treatment of patients resistant to prior checkpoint inhibitor therapy, will be presented in a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting, McCormick Place Convention Center, Chicago, Illinois, USA, June 1st, 2024 (Press release, Precision Biologics, MAY 30, 2024, View Source [SID1234643882]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Poster title: Reduction of circulating naïve Tregs and gMDSCs and low levels of soluble MICA are prognostic for efficacy of combined NEO-201 and pembrolizumab

Presentation of the poster in person will be made at the McCormick Place Convention Center in Chicago, Illinois, USA, on Saturday June 1st, 2024, Hall A from 9am – 12pm, Session: Developmental Therapeutics-Immunotherapy, poster board #9, poster # 2530.

BACKGROUND:

The employment of immune checkpoint inhibitors (ICIs), such as pembrolizumab (anti-PD-1 mAb), in cancer immunotherapy has been shown to enhance activity of the immune system against cancer cells.

Although ICIs show efficacy and improved survival of certain cancer patients, the response rate of PD-1/PD-L1 blockade against solid tumors is around 20-30% in the first line setting and significantly lower in checkpoint refractory disease. One cause identified for this low response rate is the infiltration of the tumor microenvironment (TME) by immunosuppressive cells, such as regulatory T cells (Tregs) and granulocytic myeloid-derived suppressor cells (gMDSCs). The accumulation of these immunosuppressive cells in the TME impairs the antitumor immunity triggered by ICIs.

A strategy to restore antitumor immunity and overcome tumor resistance to ICIs is to combine ICIs with anticancer drugs able to bind to and deplete Tregs and gMDSCs.

NEO-201 is a humanized IgG1 monoclonal antibody that binds to Core 1 and/or extended Core 1 O-glycans expressed by several human solid and blood tumors, as well as mature granulocytes, but it does not bind to most normal tissues and human immune cell subsets (B cells, CD4+ T cells, CD8+ T cells, NK cells, monocytes). Previous studies showed that NEO-201 can bind and mediate the killing of Tregs via CDC. Further studies presented at AACR (Free AACR Whitepaper) in 2023 showed that NEO-201 can bind and mediate the killing of gMDSCs via ADCC.

The ability of NEO-201 to mediate the killing of immunosuppressive cells served as the rationale for combination of NEO-201 with pembrolizumab in the ongoing phase II clinical trial (NCT03476681) for the treatment of patients with NSCLC, head and neck, cervical and endometrial cancers who were refractory to multiple lines of standard treatment, including ICIs.

Preliminary findings from this ongoing clinical trial presented at the CRI-ENCI-AACR in September 2023 in Milan, Italy and at the SITC (Free SITC Whitepaper) annual meeting in November 2023 in San Diego, CA, USA, revealed that, after combination treatment with NEO-201 and pembrolizumab some patients experienced durable stable disease (SD). Patients with durable SD (>84 days) demonstrated a decreasing trend in circulating gMDSCs and Tregs. Conversely, patients with progressive disease (PD) exhibited an increasing trend of circulating gMDSCs and Tregs. This preliminary data suggests that elimination of circulating gMDSCs and Tregs mediated by NEO-201 may enable patients to overcome resistance to PD-1/PD-L1 checkpoint inhibitors, in subjects for whom pembrolizumab is currently indicated and with solid tumors resistant to prior ICIs treatment.
STUDY PRESENTED AT ASCO (Free ASCO Whitepaper) 2024:

NEO-201 uses Natural Killer (NK) cells as effector cells to mediate the killing of its target cells through ADCC. Several studies reported that cancer cells inhibit NK cell antitumor activity by releasing soluble factors into the bloodstream, such as soluble MHC class 1 chain-related protein A (MICA.) Elevated serum levels of soluble MICA (sMICA) have been correlated with impairment of NK cell activity, cancer progression and metastasis.

This study reports that median serum levels of sMICA pre-treatment were 33-fold higher in patients with PD compared to patients with SD and that levels of sMICA remained elevated in patients with PD and low in patients with SD at all time points post treatment.

High levels of sMICA in patients with PD can impair NK cell activity. This impairment negatively impacts the NK cell mediated ADCC triggered by NEO-201 against cancer cells, Tregs and gMDSCs. Consequently, the effectiveness of NEO-201 and pembrolizumab treatment is reduced, leading to disease progression in these patients.

Conversely, low levels of sMICA pre- and post-treatment do not hinder the antitumoral activity of NK cells. This allows NEO-201 to effectively mediate the killing of its target cells, including cancer cells, Tregs and gMDSCs, through ADCC. As a result, this phenomenon can lead to the durable stabilization of the disease.

This study reports that low levels of sMICA, together with the reduction of both circulating Tregs and gMDSCs mediated by NEO-201, were associated with durable SD in cancer patients refractory to prior ICIs and that they could be favorable prognostic markers for clinical benefit following combination treatment with NEO-201 and pembrolizumab. Ongoing enrollment in this clinical trial will validate these findings in larger cohorts.

On May 30, 2024 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported that Richard A. Miller, M.D., president and chief executive officer, and Jeffrey Arcara, chief business officer, will conduct one-on-one meetings with investors and present a corporate overview at the Jefferies Global Health Conference, which is being held in New York from June 5-7, 2024 (Press release, Corvus Pharmaceuticals, MAY 30, 2024, View Source [SID1234643851]). The Company’s presentation will be on Wednesday, June 5 at 3:00 pm ET.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A webcast of the presentation will be available live and for 90 days following the event. The webcast may be accessed via the investor relations section of the Corvus website.

On May 30, 2024 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a clinical-stage biopharmaceutical company committed to developing novel, transformative therapies for serious metabolic and rare diseases, reported that Nevan Charles Elam, Chief Executive Officer and Founder of Rezolute, will participate in a fireside chat during the Jefferies Global Healthcare Conference on Thursday, June 6, 2024, at 1:00 p.m. ET in New York City (Press release, Rezolute, MAY 30, 2024, View Source [SID1234643867]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A live webcast will be available in the Events section of the company’s investor relations website at View Source and archived for 90 days following the event.

Management will also be participating in one-on-one investor meetings throughout the conference. Investors interested in scheduling a meeting with the Rezolute management team should contact their Jefferies representative.

On May 30, 2024 Actym Therapeutics, reported that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application to start a Phase 1 clinical trial of its lead drug candidate, ACTM-838 (Press release, Actym Therapeutics, MAY 30, 2024, View Source [SID1234643883]). The open-label monotherapy dose escalation study is designed to evaluate the safety, tolerability, payload delivery, and preliminary anti-tumor activity of escalating doses of ACTM-838, which represents the first drug candidate based on the company’s proprietary S. Typhimurium-Attenuated Cancer Therapy (STACT) platform to reach the clinic. ACTM-838 delivers immunomodulatory payloads, engineered IL-15plex (IL-15/ IL-15Ra) and STING, specifically to tumor-resident phagocytic antigen-presenting cells (APCs) in the tumor microenvironment (TME).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The immunosuppressive TME is a key challenge in the treatment of solid tumors, limiting the efficacy of many potentially effective anticancer drugs. Actym Therapeutics has developed an innovative technology to specifically deliver and express constitutively active STING in tumor-resident myeloid cells using a systemically administered therapy. IL-15plex expression adds complementary activity on B, T, and NK cells, achieving durable anti-tumor immunity," said Jason J. Luke, MD, FACP, a leading international physician-scientist specializing in the clinical development of immunotherapies for solid tumors. "Actym’s approach to modulating the TME has a unique potential to overcome these immunological barriers. Their lead candidate, ACTM-838, was shown to be safe and effective in preclinical studies and is now ready to enter the clinic."

"The IND clearance for ACTM-838 is a major milestone for Actym and potentially a significant step forward in harnessing the power of immunotherapy to treat patients with solid tumors more effectively," said Tom Smart, CEO of Actym. "It is terrific to see the vision and impressive work pioneered by Actym’s founders translated into a promising clinical-stage asset. As we advance our lead clinical program, we also look forward to further expanding the potential applications of our STACT biological platform by developing new product candidates in-house and in collaboration with pharmaceutical companies."

The Phase 1 (NCT06336148) open-label monotherapy dose escalation study with ACTM-838 will be conducted at clinical sites in the United States and Australia and will enroll patients with advanced solid tumors who have failed prior lines of therapy and have no clinically beneficial treatment options.

About STACT Biological Platform
Actym Therapeutics has engineered a new drug modality, STACT (Salmonella Typhimurium-Attenuated Cancer Therapy), harnessing the power of a genetically modified bacterial vehicle that safely introduces therapeutic payloads to activate the immune response in the tumor microenvironment (TME). It is a modular multi-faceted platform enabling cell-, microenvironment-, and tissue-targeted delivery of large combinatorial multiplexed payloads via safe systemic administration with engineered auxotrophy allowing for tissue-specific localization and enrichment for oncology and non-oncology indications. Expression of payloads, including therapeutic DNA, RNA, protein, peptide, and gene editing effectors, can be enabled in either the bacterial vehicle or targeted human cells. Actym’s proprietary platform enables tumor-localized expression of payloads at levels that are not tolerated systemically, and the ensuing local engagement of both innate and adaptive anti-tumor immunity.

About ACTM-838
ACTM-838 is Actym’s first clinical asset utilizing the STACT Platform to deliver immune-modulatory payloads specifically to the tumor-resident, phagocytic antigen-presenting cells (APCs) in the TME. After a rigorous process to identify optimal payloads, the locally expressed IL-15 superagonist, IL-15plex (IL-15/ IL-15Ra), and the constitutively active engineered STING (eSTING) were selected. Separately, each payload has been clinically validated to mediate anti-tumor immunity when administered locally. Combined, Actym has shown these payloads have exceptional synergistic activity in preclinical models. When expressed in the TME by ACTM-838, their complementary mechanisms result in an effective durable anti-tumor immunotherapy that can be safely administered systemically.

Engineered to be auxotrophic for adenosine metabolites, ACTM-838 localizes to the TME where it survives and proliferates in the adenosine-rich tumor milieu. It is phagocytosed by APCs and delivers IL-15-plex and eSTING transgenes to these cells that subsequently express the proteins in the local TME. Phagocytosis of the accumulated STACT chassis in the TME initiates activation of innate immunity. Local expression of eSTING further stimulates the innate immune system by triggering type I interferon (IFN) pathways and other cytokines. This switches the immunosuppressive TME from a pro-tumor Th2/M2 TME to an anti-tumor Th1/M1 and activated NK immune phenotype, priming a new T cell response. Locally expressed IL-15-plex additionally supports the activation and viability of NK and B cells as well as existing and newly primed T cells. Through this multifaceted mechanism, ACTM-838 engages both innate and adaptive immunity to generate a comprehensive, robust, and durable anti-tumor immune response in the body. The Phase 1 clinical study of ACTM-838 is designed to establish safety, payload delivery, and proof-of-mechanism of the STACTÔ biological platform and ACTM-838 in humans.