NorthWest Biotherapeutics Inc (NWBO)

[ae kusterer]

CSF-1R inhibitor (CSF-1Ri; PLX3397, Daiichi-Sankyo)


"We have planned a series of novel pre-clinical studies to re-polarize myeloid cells, to optimize how the timing and sequence of immunotherapy can influence ant-tumor immunity, and a new clinical trial to test the first-in-human combination of a new brain penetrant CSF-1R inhibitor (CSF-1Ri; PLX3397, Daiichi-Sankyo) with DC vaccination and PD-1 mAb blockade (Pembrolizumab, Merck) in patients with newly diagnosed GBM."

https://classic.clinicaltrials.gov/ct2/show/NCT05280470

https://clinicaltrials.gov/study/NCT04707248


https://www.merck.com/news/daiichi-sankyo-and-merck-announce-global-development-and-commercialization-collaboration-for-three-daiichi-sankyo-dxd-adcs/

Daiichi Sankyo and Merck Announce Global Development and Commercialization Collaboration for Three Daiichi Sankyo DXd ADCs
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October 19, 2023 7:30 pm ET

Collaboration combines Daiichi Sankyo’s proven ADC expertise and DXd technology with Merck’s deep experience in oncology and clinical development capabilities to advance and expand the reach of ADCs for patients across multiple types of cancer

Daiichi Sankyo and Merck to co-develop and co-commercialize patritumab deruxtecan, ifinatamab deruxtecan and raludotatug deruxtecan worldwide except for Japan where Daiichi Sankyo retains exclusive rights

Merck to pay Daiichi Sankyo a $4 billion upfront payment in addition to $1.5 billion in continuation payments over the next 24 months, and may make additional payments of up to $16.5 billion contingent upon the achievement of future sales milestones, for a total potential consideration of up to $22 billion

BASKING RIDGE, N.J. & RAHWAY, N.J., October 19, 2023 – Daiichi Sankyo (TSE: 4568) and Merck (known as MSD outside of the United States and Canada) (NYSE: MRK) have entered into a global development and commercialization agreement for three of Daiichi Sankyo’s DXd antibody-drug conjugate (ADC) candidates: patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd). The companies will jointly develop and potentially commercialize these ADC candidates worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply.

All three potentially first-in-class DXd ADCs are in various stages of clinical development for the treatment of multiple solid tumors both as monotherapy and/or in combination with other treatments. Patritumab deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in December 2021 for the treatment of patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) with disease progression on or after treatment with a third-generation tyrosine kinase inhibitor (TKI) and platinum-based therapies. The submission of a biologics license application (BLA) in the U.S. is planned by the end of March 2024 for patritumab deruxtecan, which is based on data from the HERTHENA-Lung01 Phase 2 trial (ClinicalTrials.gov; NCT04619004) recently presented at the IASLC 2023 World Conference on Lung Cancer and simultaneously published in the Journal of Clinical Oncology.

Ifinatamab deruxtecan is currently being evaluated as monotherapy in IDeate-01 (ClinicalTrials.gov; NCT05280470), a Phase 2 clinical trial in patients with previously treated extensive-stage small cell lung cancer (SCLC). Updated results from a subgroup analysis of a Phase 1/2 trial of ifinatamab deruxtecan in SCLC were recently presented at the IASLC 2023 World Conference on Lung Cancer. Raludotatug deruxtecan is currently being evaluated in a first-in-human Phase 1 clinical trial (ClinicalTrials.gov; NCT04707248) and updated results in patients with advanced ovarian cancer will be presented at the upcoming European Society for Medical Oncology (ESMO) Congress 2023.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

“The promising results from clinical trials of patritumab deruxtecan, ifinatamab deruxtecan and raludotatug deruxtecan continue to demonstrate the broad applicability of Daiichi Sankyo’s DXd ADC technology across multiple targets, with each of these medicines having the potential to change clinical practice as has been already seen with ENHERTU®,” said Sunao Manabe, Representative Director, Executive Chairperson and CEO, Daiichi Sankyo Company, Limited. “As Daiichi Sankyo continues its transformation into a global oncology leader by increasingly building our infrastructure and talent, we recognize that a collaboration with Merck, a company with remarkable oncology experience and strong in-house development capabilities and resources, will help us deliver on our obligation to deliver these potential new DXd ADCs to more patients as quickly as possible.”

“At Merck, we continue to augment and diversify our oncology pipeline while building on our immuno-oncology foundation,” said Robert M. Davis, Chairman and Chief Executive Officer, Merck. “The pioneering work by Daiichi Sankyo scientists has highlighted the far-reaching potential of ADCs to provide meaningful new options for patients with cancer. We look forward to forging this collaboration to deliver the next generation of precision cancer medicines, driven by our mutual compassion for patients around the world.”

Financial highlights

Under the terms of the agreement, Merck will pay Daiichi Sankyo upfront payments of $1.5 billion for ifinatamab deruxtecan due upon execution; $1.5 billion for patritumab deruxtecan, where $750 million is due upon execution and $750 million is due after 12 months; and $1.5 billion for raludotatug deruxtecan, where $750 million is due upon execution and $750 million is due after 24 months. Merck also will pay Daiichi Sankyo up to an additional $5.5 billion for each DXd ADC contingent upon the achievement of certain sales milestones. When combined with the additional refundable upfront payment of $1 billion described below, total potential consideration across the three programs is up to $22 billion.

Merck may opt out of the collaboration for patritumab deruxtecan and raludotatug deruxtecan and elect not to pay the two continuation payments of $750 million each that are due after 12 months and 24 months, respectively. If Merck opts out of patritumab deruxtecan and/or raludotatug deruxtecan, the upfront payments already paid will be retained by Daiichi Sankyo and rights related to such DXd ADCs will be returned to Daiichi Sankyo.

As referenced above, Merck will pay an additional upfront payment of $1 billion ($500 million each for patritumab deruxtecan and ifinatamab deruxtecan), a pro-rated portion of which may be refundable in the event of early termination of development with respect to each program. For raludotatug deruxtecan, Merck will be responsible for 75% of the first $2 billion of R&D expenses. Except as outlined above with respect to R&D expenses, the companies will equally share expenses as well as profits worldwide, except for Japan where Daiichi Sankyo retains exclusive rights and Merck receives a royalty based on sales revenue. Daiichi Sankyo will generally book sales worldwide.

In aggregate, the three programs have multi-billion dollar worldwide commercial revenue potential for each company approaching the mid-2030s.

The impact on Daiichi Sankyo’s consolidated results for the fiscal year ending March 31, 2024 will be announced at an appropriate time in the future. The collaboration is expected to contribute to enhancing the corporate and shareholder value of Daiichi Sankyo over the medium to long term.

In conjunction with this transaction, Merck will record an aggregate pretax charge of $5.5 billion, or approximately $1.70 per share, reflecting the $4 billion upfront payment and the $1.5 billion in continuation payments. The impact of this charge will result in a reduction in both fourth-quarter and full-year 2023 GAAP and non-GAAP results. In addition, Merck will invest in the pipeline assets and incur costs to finance the transaction, resulting in a negative impact to EPS of approximately $0.25 in the first 12 months following the close of the transaction.

About the DXd ADC portfolio of Daiichi Sankyo

DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops, and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2022 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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https://trp.cancer.gov/spores/abstracts/ucla_brain.htm


UCLA SPORE in Brain Cancer
University of California, Los Angeles
Principal Investigator:
Linda Liau, MD, PhD, MBA
Linda Liau, MD, PhD, MBA

Principal Investigator Contact Information
Overview
Project 1: Targeting immunotherapy-induced resistance with DC vaccination and immune modulation
Project 2: Overcoming drug-induced resistance to intrinsic apoptosis in glioblastoma
Project 3: Strategies against radiation-induced cellular plasticity in glioblastoma
Administrative Core
Biospecimen and Pathology Core (BiPC)
Neuro-Imaging Core (NIC)
Biostatistics and Bioinformatics Core (BBC)
Developmental Research Program
Career Enhancement Program
Institutional SPORE Website
Principal Investigator Contact Information
Linda Liau MD, PhD, MBA
Professor and W. Eugene Stern Chair
Department of Neurosurgery
University of California, Los Angeles
300 Stein Plaza, Suite 564
Los Angeles, California 90095-6901
Tel: [phone]

Overview
The objectives of the UCLA SPORE in Brain Cancer are to contribute significantly to progress in the diagnosis, prognosis, and treatment of brain cancer with a particular focus on developing novel strategies to overcome the problem of treatment-induced resistance. In order to achieve these translational research goals of our program, we propose three main projects involving:

Project 1: Targeting immunotherapy-induced resistance with DC vaccination and immune modulation
Project 2: Overcoming drug-induced resistance to intrinsic apoptosis in glioblastoma
Project 3: Strategies against radiation-induced cellular plasticity in glioblastoma

These translational research projects will be supported by shared resource cores in administration, biospecimen/pathology, neuroimaging, and biostatistics/bioinformatics. Our program will also be responsive to SPORE themes by incorporating Developmental Research and Career Enhancement Programs in order to foster new approaches for assessing and treating brain cancer.

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Project 1: Targeting immunotherapy-induced resistance with DC vaccination and immune modulation
Project Co-Leaders:
Robert M. Prins, PhD (Basic Science Leader)
Linda M. Liau, MD, PhD, MBA (Clinical Science Leader)

The overall goals of this project are to investigate mechanisms of immune evasion following treatment with dendritic cell (DC) vaccines, and to develop rational combinations of immunotherapeutic strategies to overcome the immunosuppressive milieu of the brain tumor microenvironment. We previously found that, in addition to inducing T-cell infiltration into brain tumors, DC vaccination + anti-PD1 blockade may also create a pro-inflammatory environment within the tumor that induces the immigration of immunosuppressive myeloid cells (TIM). TIM are phenotypically similar to the myeloid cells that attenuate the T-cell response to chronic viral infections, and may counteract the anti-tumor T-cell responses induced by DC vaccination. Therapies that target myeloid cells within the tumor microenvironment represent a promising new strategy. As such, inhibition of these myeloid cells using a CSF-1R inhibitor, in conjunction with autologous tumor lysate-pulsed DC vaccination (ATL-DC) and PD-1 mAb blockade, resulted in significantly prolonged survival in tumor-bearing animals with large, well-established intracranial gliomas. Our hypothesis is that myeloid cells mediate adaptive immune resistance in response to T-cell activation induced by immunotherapy. We have planned a series of novel pre-clinical studies to re-polarize myeloid cells, to optimize how the timing and sequence of immunotherapy can influence ant-tumor immunity, and a new clinical trial to test the first-in-human combination of a new brain penetrant CSF-1R inhibitor (CSF-1Ri; PLX3397, Daiichi-Sankyo) with DC vaccination and PD-1 mAb blockade (Pembrolizumab, Merck) in patients with newly diagnosed GBM. A better understanding of the biology of these cellular interactions will provide insight into more effective ways to induce therapeutic anti-tumor immune responses for this deadly type of brain tumor.

Aim 1: To identify the optimal timing and sequence by which immunotherapy alters the local tumor-infiltrating immune response in syngeneic murine glioma models and in recurrent glioblastoma patients.

Aim 2: To conduct a new first-in-human Phase I clinical trial of ATL-DC vaccination in conjunction with CSF-1R inhibitor (PLX3397) and PD-1 mAb (Pembrolizumab) blockade, and develop predictive immunological and imaging biomarkers.

Aim 3: To elucidate the immunotherapy-induced resistance mechanisms by which immuno-suppressive myeloid cells inhibit anti-tumor immune responses in pre-clinical animal models and in newly diagnosed glioblastoma patients.

Figure for Project 1. Depiction of the critical immune components that regulate effective anti-tumor immune responses for malignant gliomas.
Figure for Project 1. Depiction of the critical immune components that regulate effective anti-tumor immune responses for malignant gliomas.

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Project 2: Overcoming drug-induced resistance to intrinsic apoptosis in glioblastoma
Project Co-Leaders:
David Nathanson, PhD (Basic Science Leader)
Timothy Cloughesy, MD (Clinical Science Leader)

Glioblastoma (GBM) tumors are defined by high resistance to therapy-induced cell death. Through a combination of molecular and functional profiling of the intrinsic apoptotic machinery, we have identified that all GBM are comprised of two molecular intrinsic apoptotic blocks — MCL-1 and BCL-xL — to prevent tumor cell death. The goal of Project 2 is to translate rationally-designed drug combinations, consisting of new and pre-existing clinical agents, that selectively ablate the GBM dual apoptotic barrier to promote tumor cell death and induce durable clinical responses in patients.

Aim 1: To investigate whether a novel, antibody drug conjugate with a potent warhead against an essential apoptotic block has anti-tumor effects when combined with TMZ/radiation or a new, clinical brain penetrant EGFR TKI in pre-clinical GBM models.

Aim 2: To conduct a “window of opportunity” clinical trial to explore whether these new clinical drugs can ablate the two intrinsic apoptotic blocks in recurrent GBM patients.

Aim 3: To identify potential mechanisms of resistance to targeting the intrinsic apoptotic machinery in diverse pre-clinical GBM samples.

Together, the studies proposed in this application present a new therapeutic paradigm through specific manipulation of intrinsic apoptotic pathways in malignant glioma and have the long-term potential to shift current approaches in glioma therapy.

Figure for Project 2. All GBM have a dual apoptotic barrier — MCL1 and BCL-xL. Drug perturbations remove the MCL1 block in a genotype specific manner, creating an exclusive dependency on BCL-xL for survival. For EGFR TKI, changes in FDG uptake is a surrogate for ablation of MCL1
Figure for Project 2. All GBM have a dual apoptotic barrier — MCL1 and BCL-xL. Drug perturbations remove the MCL1 block in a genotype specific manner, creating an exclusive dependency on BCL-xL for survival. For EGFR TKI, changes in FDG uptake is a surrogate for ablation of MCL1

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Project 3: Inhibition of radiation-induced phenotype conversion in glioblastoma
Project Co-Leaders:
Frank Pajonk, MD, PhD (Basic Science Leader)
Leia Nghiemphu, MD (Clinical Science Co-Leader)
Albert Lai, MD, PhD (Clinical Science Co-Leader)

The overarching goal of Project 3 is to improve radiotherapy (RT) outcome for patients suffering from glioblastoma (GBM). In our last SPORE funding period, we used patient-derived glioblastoma cell lines, patient-derived orthotopic xenografts (PDOXs), and dopamine receptor antagonists (DRAs) to understand how glioma cells react to the combination of radiation and dopamine receptor inhibition. We found that the combination of RT with DRAs upregulated the fatty acid/cholesterol biosynthesis pathway, and that blocking this pathway led to markedly increased survival in tumor-bearing mice. We therefore hypothesize that blocking the radiation-induced phenotype conversion of non-stem GBM cells into radiation-resistant glioma-initiating cells using the dopamine receptor antagonist quetiapine (QTP) and statins improves radiation responses, generates an exploitable metabolic vulnerability, and can be safely applied in patients with recurrent glioblastoma.

Aim 1: To optimize the timing, sequence, and bioavailability of combination treatment with RT/QTP and statins that induces alterations in lipid metabolism and extends survival in tumor-bearing animal models

Aim 2: To test if RT/QTP induces changes in lipid metabolism that can lead to a vulnerability to be targeted for therapeutic gain in a first-in-human combination Phase I clinical trial of RT/QTP +/- statins

Aim 3: To determine the mechanisms by which RT/QTP-induced changes in lipid metabolism may be reversed by statins and prolong survival

Figure for Project 3. Compared to radiation treatment alone, a combination of radiation and the dopamine receptor antagonist quetiapine significantly improves the median survival in mouse models of glioblastoma. At the same time, this combination treatment up-regulates gene expression of key enzymes in the mevalonate pathway with subsequent up-regulation of cholesterol biosynthesis. Targeting the rate-limiting enzyme in the mevalonate pathway, HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), using the statin simvatstain down-regulates cholesterol biosynthesis in glioma cells. A triple combination of radiation, quetiapine and simvastatin further improves median survival in mouse models of glioblastoma.
Figure for Project 3. Compared to radiation treatment alone, a combination of radiation and the dopamine receptor antagonist quetiapine significantly improves the median survival in mouse models of glioblastoma. At the same time, this combination treatment up-regulates gene expression of key enzymes in the mevalonate pathway with subsequent up-regulation of cholesterol biosynthesis. Targeting the rate-limiting enzyme in the mevalonate pathway, HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), using the statin simvatstain down-regulates cholesterol biosynthesis in glioma cells. A triple combination of radiation, quetiapine and simvastatin further improves median survival in mouse models of glioblastoma.

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Administrative Core
Core Directors:
Linda M. Liau, MD, PhD, MBA (Core Director)
Timothy Cloughesy, MD (Core Co-Director)
Robert M. Prins, PhD (Core Co-Director)

The Administrative Core is responsible for the oversight and daily functions of the SPORE and provides organizational leadership for the overall successful conduct of the program. It provides organizational leadership and administrative support for all of the aspects of the SPORE, including coordination and communication between all investigators and committee members. It provides scientific management, including ongoing management and scientific review of all projects and cores to ensure that the stated scientific goals of the SPORE are met.

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Biospecimen and Pathology Core (BiPC)
Core Directors:
Fausto J. Rodriguez, MD (Core Director)
Harley I. Kornblum, MD, PhD (Core Co-Director)
David A. Nathanson, PhD (Core Co-Director)

The Biospecimen and Pathology Core (BiPC), a biorepository and multifaceted research resource, provides critical support for the translational and diagnostic/therapeutic studies of the three major UCLA Brain SPORE projects, which are directed at understanding glioma biology and developing novel therapeutic approaches for brain cancer. In addition, the BiPC supports various developmental research projects and career enhancement programs. The SPORE projects have a critical need for high-quality brain tumor biospecimens, associated clinical and molecular annotations, histology, tissue microdissection, immunohistochemistry and characterization of models systems including neurospheres and xenografts. Neuropathology and biobanking expertise exist to accomplish the research aims and tightly interacts with the other cores.

Aim 1: To optimally collect, store, and distribute high-quality brain tumor biospecimens with detailed clinical and molecular annotations (tumor tissue, blood, urine, and cerebrospinal fluid) and implement biobanking best practices.

Aim 2: To perform molecular characterization of patient-derived tumor tissue and specific project models using histologic analysis, immunohistochemistry and genomic tools, including characterization of the tumor microenvironment and apoptotic machinery and single-cell RNA sequencing.

Aim 3: To create, provide, and characterize novel human biospecimen derivatives, gliomaspheres, patient-derived orthotopic xenografts (PDOX), and organoids that represent the molecular diversity of glioblastoma.

Figure for Biospecimen and Pathology Core. This figure shows the workflow of the Core with respect to tissue collection, and the development and characterization of relevant models
Figure for Biospecimen and Pathology Core. This figure shows the workflow of the Core with respect to tissue collection, and the development and characterization of relevant models.

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Neuro-Imaging Core (NIC)
Core Director(s):
Benjamin M. Ellingson, PhD (Core Director)
Johannes Czernin, MD (Core Co-Director)

The goal of the Neuro-Imaging Core (NIC) is to provide advanced MRI and PET imaging support with established reliability and consistency to SPORE project investigators for their respective projects. The NIC uses quantitative µMRI and µPET for pre-clinical imaging (Aim 1), state-of-the-art MR and PET imaging acquisition, advanced post-processing, and novel analysis tools for clinical imaging of patients in novel clinical trials (Aim 2), and professional expertise and resources for traditional and enhanced radiographic response assessment for the clinical trials (Aim 3).

For Project 1, we theorize that tumors treated with DC vaccination and immune modulation will result in significantly higher uptake on immunoPET (89Zr-IAB22M2C Anti-CD8+ Minibody PET) and a significant decrease in tumor T2* on TAM-sensitive ferumoxytol MRI.

NIC strategy for Project 1.
For Project 2, we theorize that a combined imaging biomarker — simultaneous 18F-FDG PET and pH-weighted CEST-EPI — may be a valuable imaging biomarker for glycolytic flux, which can be perturbed using EGFR inhibition (in EGFR altered GBM) or chemoradiation (in p53 wild type GBM).

NIC strategy for Project 2.
For Project 3, we theorize that radiation therapy changes the microstructure of the subventricular zone (SVZ), known to harbor adult neural stem cells, as measured via diffusion MRI.

NIC strategy for Project 3.
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Biostatistics and Bioinformatics Core (BBC)
Core Directors:
Gang Li, PhD (Core Director)
Thomas Graeber, PhD (Core Co-Director)

The overarching goal of the Biostatistics and Bioinformatics Core of the UCLA Brain SPORE is to provide comprehensive support in the areas of biostatistics and bioinformatics for all research projects, developmental research and career enhancement programs, and other cores of the UCLA SPORE in Brain Cancer. This Core has two specific aims:

Aim 1: Biostatistics Support: Provide SPORE investigators broad-based statistical support for the individual SPORE projects. This includes statistical advice on study design, analysis and interpretation of experimental results, preparation of manuscripts, development and submission of new grant applications, data management, and the design, analysis, conduct, and monitoring of SPORE investigator-initiated clinical trials. Core 3 also develops relevant innovative methodologies and analytical tools that address specific needs from SPORE projects.

Aim 2: Bioinformatics Support: Provide infrastructure and bioinformatics leadership to design and carry out projects using high-throughput technologies, such as genomic, transcriptomic, and/or lipidomic data from tumors and/or immune cells, from bulk tissue and/or single cell next generation sequencing (NGS), and from patient tumors involved in clinical trials and from preclinical xenograft and immunocompetent mouse models. Up-to-date bioinformatics software and pipelines are provided.

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Developmental Research Program
Program Director:
Robert M. Prins, PhD

The goal of the UCLA SPORE in Brain Cancer Developmental Research Program (DRP) is to foster the exploration of innovative research ideas through the funding of pilot developmental research projects in the field of brain cancer. This program will identify new, innovative projects for funding that will constantly renew the vigor of our Brain SPORE research portfolio and add to, augment, or replace current major research projects. We expect to select three highly innovative proposals for funding each year.

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Career Enhancement Program
Program Director:
Linda M. Liau, MD, PhD, MBA

A central mission of the UCLA SPORE in Brain Cancer is to stimulate, recruit, develop, and retain new investigators in the field of brain tumor research, with particular focus on translation of scientific discoveries to novel clinical applications. The UCLA SPORE in Brain Cancer Career Enhancement Program (CEP) provides a research support resource that allows junior faculty to transition to independent investigator status with adequate peer-reviewed funding, and helps established investigators to focus or redirect their research to the area of brain cancer. Each year, we anticipate supporting two to three highly innovative candidates with CEP funds.

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