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Immune-Onc Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating IO-108, a Novel Antagonist Antibody Targeting LILRB2 (ILT4), in Patients With Advanced Solid Tumors

On October 13, 2021 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting immunosuppressive myeloid checkpoints, reported that the first patient has been dosed in the Company’s first-in-human clinical trial of IO-108, a novel antagonist antibody targeting the myeloid checkpoint Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4) for the treatment of solid tumors (Press release, Immune-Onc Therapeutics, OCT 13, 2021, View Source [SID1234591194]).

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"The first patient dosed in our Phase 1 clinical trial for IO-108 represents a critical milestone in advancing the development and understanding of Immune-Onc’s novel myeloid checkpoint inhibitors targeting the LILRB family of immune inhibitory receptors. We believe our scientific platform holds vast promise and today’s news reflects our commitment to rapidly advancing programs in our portfolio that have the potential to improve outcomes for cancer patients," said Paul Woodard, MD, chief medical officer of Immune-Onc. "With enrollment now underway, we look forward to reporting top line data next year."

The Phase 1, multicenter, dose-escalation study will consist of a monotherapy cohort and a combination therapy cohort to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IO-108 alone and in combination with pembrolizumab, an anti-PD-1 antibody. Biomarkers will be assessed to enable a mechanistic understanding of clinical data and inform future trials. This study may also provide an opportunity to identify preliminary efficacy signals. After determination of the recommended Phase 2 dose, Immune-Onc plans to evaluate the efficacy, safety, and tolerability of IO-108 in combination with pembrolizumab and as monotherapy in indication-specific expansion cohorts.

IO-108 binds to LILRB2 with high affinity and specificity and blocks the interaction of LILRB2 with multiple ligands that are involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A, and CD1d. In preclinical studies, treatment of various primary human immune cell systems containing myeloid cells with IO-108 results in enhanced pro-inflammatory responses to multiple stimuli that are relevant to anti-tumor immunity. As a single agent, IO-108 reverses the anti-inflammatory myeloid cell phenotype that results from "tumor conditioning" and promotes the differentiation of monocytes into pro-inflammatory dendritic cells. Moreover, IO-108 potentiates the effect of PD-1 blocking antibodies on CD4+ T cell activation in co-cultures with allogeneic macrophages. In mouse models IO-108 inhibits the growth of solid tumors, which is associated with enhanced T cell responses. Together these data demonstrate that IO-108 has the potential to provide additive or synergistic benefit in combination with standard-of-care immunotherapies and/or immunogenic therapies for solid tumors that are both resistant and sensitive to T-cell checkpoint inhibitors.

ABOUT LILRB2 (ILT4)

LILRB2, also known as ILT4, is expressed mostly on myeloid cells, including monocytes, dendritic cells, macrophages, and neutrophils. In solid tumors, interaction of LILRB2 with tumor microenvironment (TME) relevant ligands, including HLA-G, ANGPTLs, SEMA4A, and CD1d, makes myeloid cells pro-tumorigenic (tolerating or promoting tumor growth) and promotes tumor immune evasion.

Rhizen Pharmaceuticals AG Announces First Patient Dosing in a Phase II Study of Tenalisib (RP6530) in Locally Advanced or Metastatic Breast Cancer Patients

On October 13, 2021 Rhizen Pharmaceuticals AG (Rhizen), a Switzerland-based privately held, clinical-stage oncology & inflammation-focussed biopharmaceutical company reported that it has commenced dosing in a phase II trial to evaluate Tenalisib (RP6530; isoform selective dual PI3K δ/γ inhibitor with additional SIK3 activity) in patients with locally advanced or metastatic breast cancer (Press release, Rhizen Pharmaceuticals, OCT 13, 2021, View Source [SID1234591193]). This multi-center, randomized phase II study is being conducted in eastern Europe and is designed to assess Tenalisib’s anti-tumor activity and safety across two dose levels. The study also includes translational assessments intended to delineate the effect of Tenalisib’s multivalent mechanism on relevant cytokines/chemokine levels and gene expression changes within the tumor microenvironment.

Rhizen indicated that Tenalisib, in addition to its selective dual PI3K δ/γ inhibitory activity, also has Salt-Inducible Kinase 3 (SIK3) activity via its principal metabolite, that could potentially contribute to its chemo-sensitization effect as observed in its preclinical studies, especially in breast cancer. Rhizen hopes to establish the single agent activity of Tenalisib in this current study after which it plans to expand the assessment across additional solid tumor indications and combinations both with chemotherapeutic agents and with immune-checkpoint inhibitors.

"PI3K inhibition continues to remain a relevant therapeutic intervention across tumor types given the importance of its signalling in tumor development. We have demonstrated our ability to develop safe and differentiated isoform selective PI3K inhibitors that can withstand the rigors of development and be integrated into clinical practice" said Swaroop Vakkalanka, Founder & CEO of Rhizen Pharma. Swaroop also added that "This is a sentinel study that we expect will pave the way for Tenalisib’s potential to be expanded beyond haematological cancers into solid tumors, given its stellar safety profile, multivalent activity and consequent combinability."

About Tenalisib (RP6530):

Tenalisib (RP6530) is a highly selective, next-generation, orally active, dual PI3K δ/γ inhibitor with additional SIK3 activity, that is currently in phase II clinical development for haematological malignancies & solid tumors. Tenalisib has been granted US FDA Fast Track & Orphan-Drug Designations for treatment of r/r PTCL and CTCL and had recently published data from its phase II study evaluating Tenalisib both as monotherapy and in combination with Romidepsin in r/r PTCL & CTCL which showed robust responses of ~75% ORR in r/r PTCL and ~54% in r/r CTCL. The combination was well tolerated with no additional toxicities noted over & above those of the individual agents, confirming Tenalisib’s superior safety profile in its class. Overall, Tenalisib has been studied in over 165 patients across studies till now and has shown potentially better safety outcomes vis-à-vis other agents in the PI3K class.

Tarveda Therapeutics to Present at Solebury Trout/BMO Private Company Showcase

On October 13, 2021 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company developing a new class of potent and selective precision oncology medicines, which it refers to as Pentarin miniature drug conjugates, reported that Brian Roberts, President and Chief Executive Officer, will present virtually at the Solebury Trout/BMO Fall 2021 Private Company Showcase on Thursday, October 14 (Press release, Tarveda Therapeutics, OCT 13, 2021, View Source [SID1234591192]).

The presentation details are as follows:

Solebury Trout/BMO Fall 2021 Private Company Showcase
Date: Thursday, October 14
Time: 9:40am Eastern Time
Location: Virtual – register to attend

Twist Bioscience and the Broad Institute Create Custom Whole Exome Target Enrichment Panel for Clinical Research

On October 13, 2021 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported an agreement with the Broad Institute for the distribution of a customized next-generation sequencing (NGS) target enrichment exome panel designed for the identification and research of a wide range of cancer, rare and inherited disease genes from patient samples (Press release, Twist Bioscience, OCT 13, 2021, View Source [SID1234591190]). Twist will market this expert-developed exome panel as the Twist Alliance Clinical Research Exome.

The Twist Alliance Clinical Research Exome helps support the Broad Institute Genomics Platform and was designed using validated data from clinical patient samples. The panel leverages Twist’s flexible NGS platform to easily and quickly customize content, resulting in a comprehensive survey of the exome with supplemental enrichment of clinically relevant areas of the genome related to cancer as well as rare and inherited diseases. By leveraging the best-in-class uniformity of Twist NGS probes, the assay enables a per sample cost and throughput efficiency that Broad has already leveraged to process more than 250,000 samples to date, keeping it on the leading edge of exome sequencing.

"Exome sequencing has long been a key part of our sequencing efforts for large cancer and germline research studies. Our development with Twist has leveraged many of our learnings on the technical side and pulls in knowledge from collaborating investigators to provide an enhanced exome that will increasingly span both research and clinical applications in which results are returned to patients" said Stacey Gabriel, senior director of the Broad Institute Genomics Platform.

The Twist Alliance Clinical Research Exome will be available for customers in mid-October. The full design of this panel includes the Twist Core exome, the mitochondrial genome, and additional validated coding and non-exonic regions of interest such as the ACMG73 genes, supplemental coverage of regions from OMIM and COSMIC, and specific Broad-defined targets. To see Broad’s Director of Genomics Research and Development Brendan Blumenstiel presenting data on the panel, visit: View Source

"Typically, in cancer research studies, there is a great need to focus sequencing efforts on particular genes or mutations but often with a small number of samples available. Leveraging the Broad’s vast expertise, together we have developed a specialized custom panel that enables deeper sequencing, producing validated genetic variants that could be used for therapeutic intervention," said Emily M. Leproust, PhD, chief executive officer and co-founder of Twist Bioscience. "We are thrilled to bring this important tool to our customers to drive deep insights into research and potentially therapeutic development."

About Twist Alliance Panels

In partnership with leading research institutions from around the world, Twist has curated a collection of high-quality target enrichment panels for applications ranging from carrier screening to cancer diagnostics and whole exome sequencing. The Twist Alliance Panels combine the strengths of precise, highly uniform oligonucleotide synthesis with the specialty expertise of leading scientific research partners.

Well designed, custom target enrichment panels enable increased sequencing depth on target genes while reducing overall

Susan G. Komen® Announces $1.5 Million in Grants for Metastatic Breast Cancer Research

On October 13, 2021 Susan G. Komen, the world’s leading breast cancer organization, reported the awarding of $1.5 million for three new research projects that examine three unique areas focused on metastatic breast cancer (MBC) (Press release, Susan G Komen, OCT 13, 2021, View Source [SID1234591189]). The grants are part of the Susan G. Komen Metastatic Breast Cancer Collaborative Research Initiative, an innovative, first-of-its-kind collaboration between Komen, Duke Cancer Institute and the University of North Carolina Lineberger Comprehensive Cancer Center. The initiative is an effort to pair researchers from each of the organizations to work together to address significant gaps in our knowledge about MBC to advance patient care and improve patient outcomes.

"We know that finding the cures for breast cancer will only be accomplished by working together through innovative research," said Paula Schneider, Komen’s president and CEO. "It’s this strong belief in the power of collaboration to advance discovery that led to this novel partnership between some of the leading researchers at two institutions that are known for their rivalry."

These three grants fall under Komen’s two primary research priorities, which are to find new ways to prevent, detect, and treat metastatic and aggressive breast cancers, as well as to understand and overcome the inequities that lead certain people and communities to have higher rates of mortality from breast cancer.

"This bold investment by Komen and its supporters is aimed at changing our fundamental understanding of metastatic breast cancer," said UNC Lineberger Director Shelley Earp, M.D. "Combining the creative minds of two of the country’s premier cancer centers is the way to probe the longstanding problem of breast cancer spread. Each of these approaches will yield groundbreaking knowledge to develop better, more effective treatments by harnessing a patient’s own immune system and will identify the biological and societal drivers that contribute to disparities in breast cancer outcomes among Black and white women."

"We are very grateful to Susan G. Komen for their long-term dedication to improving approaches to the prevention, diagnosis and treatment of breast cancer," said Michael B. Kastan, M.D., Ph.D., executive director of the Duke Cancer Institute. "Metastatic breast cancer remains a major challenge and this visionary funding mechanism brings together outstanding investigators and physicians from two neighboring institutions in collaborative projects that will make a difference for women in the state of North Carolina and around the country."

Thanks to a $500,000 lead gift by Blue Cross and Blue Shield of North Carolina (Blue Cross NC), we are able to award the Susan G. Komen and Blue Cross NC Metastatic Breast Cancer Disparities Collaborative Research Grant to:

A research team led by Drs. Jennifer Freedman and Steven Paterno of Duke Cancer Institute, and Dr. Katie Hoadley of the University of North Carolina Lineberger Comprehensive Cancer Center, who were awarded a grant to investigate how the ancestry of different populations impacts the immune response to metastatic breast cancer. The study leaders identified biological differences in certain genetic events (called RNA splicing) in tumors between those with African versus European ancestry. The team seeks to determine if these differences cause breast cancer cells to grow and spread more quickly in patients of African descent and contribute to higher metastasis and death rates among Black women. Improved understanding of these underlying molecular mechanisms may lead the way to better treatments and outcomes.
"We know that the health of our state depends on the health of all our communities – and to improve health equity, we must take a closer look at the factors that drive the disparities between Black women and metastatic breast cancer," said Dr. Kia Williams, associate medical director at Blue Cross NC. "We are excited to support Komen and researchers at UNC and Duke and eagerly await the invaluable scientific contributions to come from this collaborative effort."

Thanks to a $500,000 gift by Gilead Sciences, Inc., we are able to award the Susan G. Komen and Gilead Sciences, Inc. for North Carolina’s Metastatic Breast Cancer Collaborative Research Grant to:

A research team led by Dr. Melissa Troester of the University of North Carolina Lineberger Comprehensive Cancer Center and Dr. Terry Hyslop of Duke Cancer Institute for their project that will seek to use information on tumor biology and social factors in UNC’s long-standing Carolina Breast Cancer Study (CBCS) to understand racial differences in breast cancer metastasis and death. Researchers will also evaluate how life stress contributes to higher metastasis rates and worse breast cancer outcomes in Black women when compared to white women. They aim to develop specific interventions to reduce metastasis that consider multiple factors from basic biology to societal factors in order to improve outcomes for Black women.
"As metastatic breast cancer disproportionately impacts Black women, this innovative research to better understand evidence-based solutions to improve outcomes for Black women is crucial," said Bill Grossman, M.D., Ph.D., Senior Vice President, Oncology Therapeutics, Gilead Sciences. "Gilead is proud to support Susan G. Komen in these much-needed efforts."

Thanks to funds raised by individuals and organizations in North Carolina and across the country, Komen is able to award:

A research team led by Dr. Benjamin Vincent of the University of North Carolina Comprehensive Cancer Center and Dr. Zachary Hartman of Duke Cancer Institute with a $500,000 grant for their project to develop a personalized anti-tumor vaccine strategy for patients with advanced Triple Negative Breast Cancer that would mobilize the body’s immune system (T cells) to shut down tumor growth and metastasis.
Spearheaded by Komen Development Director Pam Kohl, who is living with MBC, the Komen Collaborative Metastatic Research Initiative seeks to raise funds with the hope of accelerating discovery by connecting leading researchers from these two leading institutions. These three grants are the initial awards from this initiative. Those interested in supporting additional collaborations can donate at www.komen.org/mbccollaborative.

"Currently, there is no cure for MBC and the treatments are difficult at best," said Kohl. "Research is HOPE for the far too many of us who are living with MBC. This disease is smart, and it is relentless, but I know that these brilliant researchers at UNC and Duke will work every day to help give us the gift of time."