On June 16, 2022 Boundless Bio, a next-generation precision oncology company developing innovative therapeutics directed against extrachromosomal DNA (ecDNA) in oncogene amplified cancers, reported to share the news that a global team of ecDNA experts comprised of several Boundless Bio scientific co-founders and led by Boundless Bio principal founder, Paul Mischel, M.D. has been awarded $25 million in funding by the National Cancer Institute (NCI*) and Cancer Research UK (CRUK) through Cancer Grand Challenges to deepen the understanding of the role of ecDNA in cancer pathogenesis (Press release, Boundless Bio, JUN 16, 2022, View Source [SID1234616050]). Cancer Grand Challenges is a unique global funding initiative founded by CRUK and the NCI, who have set ambitious challenges to assemble global teams to think creatively and make a profound difference in the fight against cancer.

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The global ecDNA research team, also known as "the Cancer Grand Challenges eDyNAmiC team", is led by Dr. Mischel, who has been at the forefront of research into the importance of ecDNA in gene amplified cancers such as EGFR amplified glioblastoma. Dr. Mischel and his team will use the funding to answer key scientific questions to further understand the biological mechanisms of ecDNA generation and function, as well as potential therapeutic strategies to help improve cancer outcomes. The multi-disciplinary research team includes the following scientific experts that are also members of Boundless Bio’s Scientific Advisory Board:

Paul Mischel, M.D., Institute Scholar, ChEM-H; Professor and Vice Chair of Research for the Department of Pathology, Stanford University
Vineet Bafna, Ph.D., Professor of Computer Science & Engineering, University of California San Diego
Howard Chang, M.D., Ph.D., Virginia and D.K. Ludwig Professor of Cancer Genomics and Genetics, Stanford University
Ben Cravatt, Ph.D., Professor and Gilula Chair of Chemical Biology, The Scripps Research Institute
Roel Verhaak, Professor and Associate Director of Computational Biology, The Florine Deschenes Roux Chair for Genomics and Computational Biology, The Jackson Laboratories
"We congratulate Paul and the eDyNAmiC team for receiving the prestigious Cancer Grand Challenges award to progress innovative research in the expanding field of ecDNA," said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. "This award further underscores the importance of ecDNA biology in cancer and our goal to bring the first ecDNA-directed therapeutics (ecDTx) into clinical trials for patients with oncogene amplified cancer. We at Boundless continue to be inspired by Dr. Mischel and the eDyNAmiC scientific team’s commitment to advancing the scientific understanding of ecDNA."

"We are thrilled to receive the NCI and CRUK award, an acknowledgement of the critical role ecDNA play in the biology of cancer," said Dr. Mischel, Professor and Vice Chair of Research for the Department of Pathology, Stanford University. "It is amazing to reflect on how rapidly the ecDNA field has come of age. With this recognition and dedicated funding for ecDNA research, we have the opportunity to further explore the pathogenesis of ecDNA in cancer with the goal of developing innovative new treatments that benefit patients with oncogene amplified cancers driven by ecDNA."

For more information on Cancer Grand Challenges, please visit: www.cancergrandchallenges.org/new-teams-2022

For more information on the eDyNAmiC team, please visit: www.cancergrandchallenges.org/teams/eDyNAmic

*The National Cancer Institute is part of the National Institutes of Health.

About ecDNA

Extrachromosomal DNA ("ecDNA") are circular units of nuclear DNA that are physically distinct from chromosomes and are found within cancer cells. ecDNA encode full length genes, including oncogenes and regulatory regions, are highly transcriptionally active, and lack centromeres. ecDNA replicate and express within cancer cells and, due to their lack of centromeres, can be asymmetrically passed to daughter cells during cell division, leading to focal gene amplification and copy number heterogeneity in cancer. By leveraging the plasticity afforded by ecDNA, cancer cells have the ability to increase or decrease copy number of select oncogenes located on ecDNA to enable survival under selective pressures, including targeted therapy, immunotherapy, chemotherapy, or radiation, thereby making ecDNA one of cancer cells’ primary mechanisms of growth, recurrence, and treatment resistance. ecDNA are not found in healthy cells but are present in many solid tumor cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes.

On June 16, 2022 Pionyr Immunotherapeutics, Inc., a company developing first-in-class Myeloid Tuning antibody therapeutics that enhance the body’s anti-tumor immunity by altering, or "tuning," immune cells within the tumor microenvironment, reported that Chief Medical Officer Leonard Reyno, M.D., will lead a discussion on myeloid cell targeting to reprogram the tumor microenvironment, modulate innate immune activity, and enhance anti-tumor immunity (Press release, Pionyr Immunotherapeutics, JUN 16, 2022, View Source [SID1234616049]). The presentation will highlight preclinical and early clinical research on Pionyr’s first in class TREM1-targeting monoclonal antibody called PY159. The presentation titled, "Reprogramming TREM1+ Myeloid Cells to Overcome Immunotherapy Resistance in Solid Tumors," takes place at the 2nd Tumor Myeloid Directed Therapies Summit on June 16, 2022.

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"Pionyr was built on the premise that the myeloid compartment is a source of provocative, untapped anti-tumor drug targets that can be harnessed to modulate the innate immunity and our natural defenses against cancer cells," said Leonard Reyno, M.D., Chief Medical Officer at Pionyr. "With first-in-class drug candidates in clinical development targeting TREM1 and TREM2 associated myeloid cells, and a preclinical program targeting MARCO, our approach demonstrates the incredible potential to improve innate immunity, overcome the limitations of checkpoint inhibitors, and illustrate a foundational approach to transforming immuno-oncology."

As part of the presentation, Pionyr will highlight the PY159 development program. PY159 is a humanized monoclonal antibody that specifically binds triggering receptor expressed on myeloid cells 1 (TREM1). The presentation will highlight:

Preclinical research demonstrating expression of TREM1 to be higher in cancerous tissues vs normal tissues
Preclinical evidence showing TREM1 as a promising therapeutic opportunity for patients with checkpoint inhibitor (CPI)-hypo-responsive or resistant tumors as the receptor is expressed on the three myeloid immuno-suppressive cell populations
In vivo model data demonstrating administration of PY159 alone or in combination with CPIs resulted in complete regressions of tumors
First in human clinical experience administering PY159 both alone and in combination with pembrolizumab including identification of target archival tumor specimens from participating patients
Outline clinical plans for further study in patients with advanced refractory solid tumors
The Tumor Myeloid-Directed Therapies Summit is the only industry-focused meeting dedicated to unlocking novel therapeutic potential of the myeloid compartment where experts come together to identify, validate and clinically progress myeloid targets to expand the oncologist’s toolkit and realize better responses by engaging myeloid anti-tumor function. It is designed for experts working directly in myeloid-directed therapies, and those in adjacent immune-oncology fields, from cell therapy to checkpoint inhibitor development.

About Myeloid Tuning

Pionyr has developed a therapeutic platform called Myeloid Tuning, a process that rebalances the tumor microenvironment (TME) to promote anti-tumor immunity. Myeloid cells are a type of immune cell and are part of a family of cell types that play an important role in both the activation and suppression of the immune response to cancer.

One such critical type of myeloid cell, tumor-associated macrophages (TAM), are a key component of the TME. TAMs are generally categorized into two functionally contrasting subtypes called M1-like and M2-like macrophages: M1-like typically exerts anti-tumor functions, including directly mediating antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; M2-like macrophages can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis and lead to tumor progression.

Myeloid Tuning effectively describes the mechanism of introducing agents that shift the balance of inhibitory myeloid cells – including M2-like TAMs – towards more inflammatory M1-like TAMs to promote anti-tumor immune responses in the TME and destroy solid tumors.

On June 16, 2022 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a late-stage clinical biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm,’ reported it entered into an agreement with PCI Pharma Services (PCI), a leading integrated global contract development manufacturing organization (CDMO), to provide importation, release and commercialization services in the United Kingdom (UK) for lenzilumab (Press release, Humanigen, JUN 16, 2022, View Source [SID1234616048]). Under the agreement, PCI will purchase lenzilumab for resale and distribution in the event a Conditional Marketing Authorization is received in the UK for use in patients hospitalized with COVID-19.

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"We continue our commercial preparation in the UK and in parallel are working closely with the Medicines and Healthcare products Regulatory Agency (MHRA) to address regulatory requirements for a potential Conditional Marketing Authorization. With its global reach, PCI will provide a critical function in the supply chain, by directly purchasing lenzilumab for further distribution in the UK and facilitating this key process for Humanigen," said Edward Jordan, Chief Commercial Officer. "It is anticipated that we will complete our response to MHRA soon after the top-line results from the ACTIV-5/BET-B clinical trial with lenzilumab are received."

If authorized, lenzilumab will offer an important treatment option to patients hospitalized with COVID-19. Hospitalizations from COVID-19 continue in the United Kingdom with more than 235,000 admitted year-to-date and with ~5,000 currently hospitalized.1 In addition, Humanigen believes that treatment with lenzilumab may deliver economic value to the healthcare system. Previously published research has demonstrated that treatment with lenzilumab may save the National Health Service over £10,000 per patient.2

Lenzilumab is an investigational product and is not approved or authorized in any country.

About Lenzilumab

Lenzilumab is a proprietary Humaneered first-in-class monoclonal antibody that has been proven to neutralize GM-CSF, a cytokine of critical importance in the hyperinflammatory cascade, sometimes referred to as cytokine release syndrome, or cytokine storm, associated with COVID-19 and other indications. Lenzilumab binds to and neutralizes GM-CSF, potentially improving outcomes for patients hospitalized with COVID-19. Humanigen believes that GM-CSF neutralization with lenzilumab also has the potential to reduce the hyperinflammatory cascade known as cytokine release syndrome common to chimeric antigen receptor T-cell (CAR-T) therapy and acute Graft versus Host Disease (aGvHD).

In CAR-T, lenzilumab successfully achieved the pre-specified primary endpoint at the recommended dose in a Phase 1b study with Yescarta in which the overall response rate was 100% and no patient experienced severe cytokine release syndrome or severe neurotoxicity. Based on these results, Humanigen plans to test lenzilumab in a randomized, multicenter, potentially registrational, Phase 3 study ("SHIELD") to evaluate its efficacy and safety when combined with Yescarta and Tecartus CAR-T therapies in non-Hodgkin lymphoma. Lenzilumab will also be tested to assess its ability to prevent and/or treat aGvHD in patients undergoing allogeneic hematopoietic stem cell transplantation.

A study of lenzilumab is also underway for patients with chronic myelomonocytic leukemia (CMML) exhibiting RAS pathway mutations. This study builds on evidence from a Phase 1 study, conducted by Humanigen, that showed RAS mutations are associated with hyper-proliferative features, which may be sensitive to GM-CSF neutralization.

On June 16, 2022 Umoja Biopharma, Inc., an immuno-oncology company pioneering off-the-shelf, integrated therapeutics that reprogram immune cells in vivo to treat patients with solid and hematologic malignancies, reported that it will have a poster presentation at the 2022 International Society for Stem Cell Research (ISSCR) Annual Meeting, to be held June 15-18, 2022 in San Francisco, California (Press release, Umoja Biopharma, JUN 16, 2022, View Source [SID1234616046]).

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On Wednesday, June 15th, Principal Scientist & iPSC Team Lead, Teisha Rowland, Ph.D., will give a poster presentation titled, "A Synthetic Cytokine Receptor Platform for Producing Cytotoxic Innate Lymphocytes as Off-the-Shelf Cancer Therapeutics." The presentation will discuss Umoja’s engineered induced pluripotent stem cell (iPSC) platform, that incorporates the synthetic cytokine receptor system rapamycin-activated cytokine receptor (RACR) platform. Umoja’s engineered iPSCs that are modified to express RACR, called RACR-induced cytotoxic innate lymphoid (iCIL) cells, drive differentiation and expansion of the cells while eliminating the need for expensive cytokines and other raw materials. The RACR platform has the potential to enable cytokine-free manufacturing and engraftment of the engineered cells in the patient without the need for toxic lymphodepletion.

"Despite the advances chimeric antigen receptor T cell therapies have provided to the oncology space, we continue to battle significant challenges that these therapies cannot address, like limited expansion capacity and scalability, manufacturing complexity, variability among patients, and the need for toxic chemotherapy administration to combat patients’ anti-allograft response," said Andy Scharenberg, M.D., co-founder and Chief Executive Officer of Umoja. "We are developing an engineered iPSC platform, including the RACR platform, to address these challenges by enabling a scalable, virtually unlimited, and simplified manufacturing of engineered, cancer-fighting cytotoxic innate lymphocytes."

On June 16, 2022 PerkinElmer Inc., a global leader committed to innovating for a healthier world, reported that it is collaborating with Novartis, a leading global medicines company, to expand newborn screening for sickle cell disease (SCD) in sub-Saharan Africa (Press release, PerkinElmer, JUN 16, 2022, View Source [SID1234616045]). PerkinElmer together with the Novartis Africa Sickle Cell Disease program aims to expand advocacy efforts to educate patients, caregivers and communities about the importance of newborn screening and early intervention with hydroxyurea (HU) and other SCD treatments.

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Newborn screening for SCD and comprehensive disease management in high-income countries like the United States has reduced mortality in children under five years old by 94%[1]. Yet, in sub-Saharan Africa which bears the highest burden of the disease, no national newborn screening program exists. This collaboration aims to galvanize governments to provide universal newborn screening as part of national health programs in support of early diagnosis and comprehensive interventions such as prophylactic penicillin, a pneumococcal vaccination and therapies like HU. With effective screening and management of SCD, governments could save many precious lives.

The Novartis Africa Sickle Cell Disease program was launched in Ghana in 2019 as an end-to-end effort that encompasses SCD screening, diagnosis, treatment, education, research and advocacy. Today this unique program has been expanded to Uganda, Tanzania, Kenya and Zambia, with plans to reach a total of 10 countries.

Among its varied contributions to the program, PerkinElmer will work toward strengthening existing SCD programs by providing training, consultations, support and related services to health care professionals and lab technicians across participating countries in sub-Saharan Africa. The Company will also help establish new lab facilities to build capacity for SCD screening in participating countries.

"As a global leader in newborn screening solutions we are pleased to be working with Novartis to assist people across sub-Saharan Africa affected by this condition," said Petra Furu, general manager, reproductive health at PerkinElmer. "By building awareness around the importance of newborn screening, our hope is that more babies receive an early diagnosis that leads to earlier treatment – ensuring they have the best possible chance of a healthy start to life."

"This collaboration with PerkinElmer reaffirms our commitment to reimagining care for sickle cell disease patients, by accelerating access to national newborn screening and hydroxyurea through public-private partnerships with local governments and other organizations," said Racey Muchilwa, Country President and the Head of Novartis sub-Saharan Africa. "We will also be educating patients, caregivers and communities on the importance of newborn screening, early intervention and treatments while elevating the capacity for healthcare professionals to address the high unmet need of SCD."

In an initiative announced in March 2021, PerkinElmer works alongside the American Society of Hematology (ASH) (Free ASH Whitepaper) and its Consortium on Newborn Screening in Africa (CONSA) to provide resources for SCD screening programs in countries throughout sub-Saharan Africa, including Ghana, Kenya, Nigeria, Uganda, Zambia, Liberia and Tanzania. Novartis announced its partnership with ASH (Free ASH Whitepaper) in early June, which will advance ASH (Free ASH Whitepaper)’s CONSA objectives to demonstrate the benefits of newborn screening and early interventions for children with SCD and create a sustainable infrastructure for SCD newborn screening.