Drug Discovery Initiative

2016 DDI Awards Application

The 2016 DDI-A Application is now available. 

Please review the eligibility guidelines HERE. 
Once you begin your application you can save your work and return to it at any time using the log-in link that you will receive via email. Please do not return to this link to continue your application as your work will not be saved; you must return to the link you receive via email to continue your work in your saved application. 
To begin a new DDI application click HERE
Applications are due Monday, April 18, 2016 at 5:00 p.m.


Please refer to the Frequently Asked Questions below for further information.
We look forward to receiving your application!




Do I have to sign the patent policy in order to apply?

Yes. You must sign the patent policy at the time of application.

What if my tech transfer office wants to negotiate the patent policy before I sign it?

If you think your tech transfer office will want to negotiate the patent policy, you must send the patent policy to them immediately and have them contact CTF to negotiate the terms immediately.

Can I still apply for a DDI even if I don't share tools in the CTF Discovery toolbox?

Yes. However, we strongly encourage you to share tools, techniques, protocols and collaborate in order to advance the field.

Do I have to sign the MTA in order to apply?

We encourage applicants to share their tools in the DDI toolbox. To do so, you must agree to the terms of the MTA by signing Form F. This is a sample MTA, and will be fully completed by you and the recipient at the time of transfer of tools.

What is ADDF-ACCESS and how does it relate to the DDI application?

Alzheimer's Drug Discovery Foundation (ADDF) and the Children's Tumor Foundation (CTF) are in a partnership to provide CTF's scientific network access to a virtual network of drug discovery experts and contract research organizations (CROs) through the ADDF ACCESS program. The program offers scientist tools to determine if they need a CRO, how to choose a CRO, how to manage a relationship with a CRO, education on the drug discovery process, and an online forum for discussions with experts. The portal allows users to customize their search for CROs based on drug discovery area and resources for guidance on CRO selection and research design.

We have entered this partnership to provide this resource to our NF scientists, especially those in the drug discovery field. The DDI exists to accelerate drug discovery for NF. By partnering with CRO, we can make the path to the clinic more efficient.


To learn more about how partnerships with CROs will streamline drug discovery efforts, please refer to this recent publication in Nature Reviews Drug Discovery:


How do I determine if I need a CRO?

Deciding when to outsource depends on a variety of factors, including in-house capabilities and the need for expert guidance. Why should you outsource?

  • Access to targeted compound libraries
  • Early stage development expertise in the following areas:
  • Assay development
  • Medicinal chemistry
  • Pharmacology
  • Pharmacokinetics and Pharmakodynamics
  • ADME, safety and toxicology studies
  • Cost and time efficiency – Evaluate overhead costs of resources, equipment, adherence to standard operating procedures (SOP), and personnel certifications for highly specialized tasks versus the costs of outsourcing. Consider how much time your personnel devote to drug discovery tasks and how long it will take to develop SOPs
  • Key platform technologies – Access to automated equipment that produce reliable, robust, and reproducible data (i.e. behavioral monitoring systems, microscopy, in vivo imaging, HPLC units, liquid handlers, plate readers)
  • Regulatory compliance – Later-stage IND-enabling studies require good lab practice (GLP) and good manufacturing practice (GMP) conditions in compliant laboratories.
  • For more information, please refer to the ADDF ACCESS Resource Center: When to Outsource


How do I choose a CRO?

Please refer to the ADDF ACCESS Resource Center: Evaluating and Selecting CROs: http://www.alzdiscovery.org/addf-access/resource-center/evaluating-and-selecting-cros

Does the cost of the CRO come out of my DDI award amount?

No, CTF will pay the CRO directly and it does not come out of your DDI award amount.



A more streamlined and efficient path to clinical development can be accomplished by partnering with contract research organizations (CROs). The Alzheimer’s Drug Discovery Foundation (ADDF) and The Children’s Tumor Foundation (CTF) have entered a partnership to provide CTF’s scientists access to a virtual network of drug discovery experts and CROs through the ADDF ACCESS program. Through the effective selection of CROs and use of their services, NF researchers may be able to accelerate their research and bring novel therapies to patients faster. Read more about the partnership Alzheimer's-Drug Discovery Foundation.

CTF Discovery Toolbox

(NOTE: Updates to this document are pending.) The new CTF Discovery Toolbox is an online list of tools for NF drug discovery - mouse models, cell lines, candidate drugs, etc. for investigators to share resources and establish collaborations. It is expected that, unless legally prevented from doing so, DDI Awardees will make tools developed under their DDI award available through the CTF Discovery Toolbox. CTF also strongly encourages researchers to voluntarily submit tools that are created outside the scope of their funding from CTF.  To improve the use and sharing of such tools, we introduced a new regulation that will make it more transparent and easier to access to any researcher: we added an upfront agreement to CTF standard conditions for the transfer of the tools, as outlined in the MTA available for download in the application. Investigators who will decide to make their tools available in the toolbox will be notified by CTF if the tool is requested, and CTF will coordinate the final agreement between the two parties.  

A link to download the CTF Discovery Toolbox Submission/Request form will be posted here shortly

DDI Recipients 2011-2015

2015 DDI Awardees 

  • Dr. Nancy Ratner, Cincinnati Children's Hospital Medical Center,Mechanisms of Resistance to MEK Inhibition in Neurofibroma
    Neurofibromatosis Type 1 (NF1) is a disorder caused by a mutation in a tumor suppressor gene that results in the formation of tumors known and neurofibromas. These neurofibromas can grow under the skin or in nerves of the peripheral nervous system. Neurofibromas are resistant to chemotherapy treatments, and surgical removal is often very difficult or impossible because the tumors are both within and outside nerves. Therefore, we aim to find drugs that reduce neurofibroma size and are potentially curative. We already found that drugs that target MEK proteins shrink most neurofibromas. In patients with NF1, the mutated gene, neurofibromin, can no longer do its proper function of turning off a protein called Ras. When Ras is on, downstream pathways (that include MEK) are also active, contributing to neurofibroma formation. By using a drug to inhibit MEK, the over-active pathway is turned off and that can shrink neurofibromas. However, both in humans and in preclinical trials in mice, inhibiting MEK doesn't always work and some are resistant to MEK inhibition. Our goal is to determine what else is being turned on during MEK inhibition so that it can also be targeted and therefore prevent drug resistance. In preliminary experiments, we identified a protein that is overexpressed after MEK inhibition, and is a signaling protein that can induce the growth movement of other cells and turn on other signaling pathways inside cells. We hypothesize that by inhibiting MEK as well as Cxcl13, we will prevent drug resistance and thereby identify increasingly successful treatment for patients with NF1.

  • Dr. Thomas A. Look, M.D., Dana-Farber Cancer Institute,Drug discovery for NF1-associated malignant peripheral nerve sheath tumors using the zebrafish model
    Malignant peripheral nerve sheath tumors (MPNSTs) are very aggressive and often metastatic soft tissue sarcomas. The prognosis is very poor, and the recurrence rate is relatively high. MPNSTs are frequently found in patients who have neurofibromatosis type 1 (NF1) disease. This disease is caused by mutation of the NF1 gene, which is among the most prevalent inherited tumor suppressor genes in humans. Currently, surgical excision is the only way to cure MPNST, although surgery is frequently not adequate because MPNSTs often metastasize and invade surrounding normal tissues and vital organs. Current chemotherapy regimens are often ineffective, and associated with significant toxicity that can severely reduce quality of life. Therefore, it is very important to identify promising drugs that can be rapidly moved into clinical trials to improve the therapy of patients with MPNSTs.

    We have developed a faithful zebrafish model of MPNSTs, by breeding together zebrafish that harbor genetically engineered inactivation of both of the duplicated zebrafish nf1 genes and p53. To identify new drugs that inhibit pathways essential for MPNST cell growth and survival, we will transplant MPNST cells from primary zebrafish tumors into very small zebrafish embryos and array these embryos into 96 well plates for incubation with the drugs. We also plan to test a collection of 1280 drugs that are FDA approved for human use for all types of diseases. In each case, we will be analyzing the drugs for their ability to reduce the numbers of MPNST tumor cells in our model. To increase the likelihood of the success of our work, we will test each of these drugs alone and also in combination with one of the most potent available targeted inhibitors of the pathway activated by NF1 loss. We are likely to identify drugs that are not currently being used for MPNST but that can rapidly be repurposed for testing in human patients. We predict that we will be likely to identify one or more FDA approved drugs or drugs in current clinical trials that will show activity against MPNSTs. Promising combinations will then be tested in human MPNST cell lines growing as xenografts in immune-deprived mice, and then will be available for testing in clinical trials. The strategy we are using is called "repurposing" because we are hoping to identify approved drugs that have been developed for a different disease that can be "repurposed" to improve the treatment of MPNSTs in NF1 patients. Our project is designed to make discoveries using the zebrafish model system that can be relatively quickly translated to improve the treatment of MPNSTs that develop in patients with Neurofibromatosis type 1.

  • Dr. Joseph Kissil, Scripps Research Institute,Assessing the anti-tumor activity of crizotinib in NF2-deficient meningioma
    Neurofibromatosis type 2 (NF2) is a disease characterized by different types of tumors including those originating from the cells that line the auditory nerve (schwannoma). There are no cures available for NF2 schwannoma and treatment options are limited to surgery that is associated with significant morbidity. We have recently identified an FDA approved drug called crizotinib, as having anti-tumor activity against these schwannomas and identified the mechanisms by which the drug exerts its effects. Since the drug is FDA approved for another type of cancer (lung cancer) and has very little side effects, it is being tested in clinical trials against other types of tumors in adults and children. Based on our findings, a trial is being initiated to test crizotinib against schwannoma in NF2 patients. We now wish to assess whether crizotinib would be useful as a drug against meningioma, which another type of tumor commonly associated with NF2. We propose to test the effects of drug treatment in cells and animal models of meningioma. Should the treatment show a desirable effect, this would indicate that the clinical trial should be expanded to include meningioma as an additional indication.

  • Dr. Andrea McClatchey, Massachusetts General Hospital, Expanded testing of centrosome-unclustering drugs in NF2-mutant tumors
    The successful development of a therapeutic strategy for any tumor requires a clear therapeutic window in which the drug negatively impacts tumor cells but not normal cells. Over duplication of centrosomes, a cellular organelle that is essential for normal cell division, occurs broadly across different tumor types and has therefore received much recent attention as a feature that distinguishes tumor from normal cells. This has led to the development of drugs that specifically target and kill cells that harbor too many centrosomes, some of which are already in clinical use. We recently identified a key role for Merlin in controlling the distribution and number of centrosomes within cells. In fact, in preliminary studies funded by a CTF DDI award we have found that NF2 deficiency alone causes particularly severe centrosome defects and that NF2-mutant schwannoma cells are exquisitely sensitive to several different centrosome-targeting drugs. Moreover, we also found that defects in centrosome number and organization are common across all types of NF2-mutant tumors that we tested, including schwannoma, meningioma, mesothelioma and renal carcinoma. We believe that this therefore represents an Achilles heel for NF2-mutant tumors. The goal of this proposal is to expand our studies to investigate the sensitivity of other NF2-mutant tumor cells, particularly meningioma, to centrosome-targeting drugs AND to test an expanded panel of centrosome-targeting drugs that act in different ways on all NF2-mutant tumor types. This will allow us to match the right drug to each tumor type and provide a necessary foundation for guiding and interpreting studies in mouse models and ultimately in humans.

  • Dr. Alexander Schulz, Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI),Establishing a protein replacement therapy for the treatment of Schwann cell-derived nerve sheath tumors
    Akin to other tumor entities, uncontrolled growth of cells is the culprit of both development and progression of Schwann cell-derived tumors (schwannomas). Based on our own work and the data of other scientists, we know that cell growth cannot just be controlled by the cell itself, but also by outside signals. The so-called 'microenvironment' has been shown to be relevant in normal development and tissue homeostasis, as well as in pathological conditions like cancer. In the case of schwannomas, this local microenvironment is determined by peripheral nerves containing Schwann cells and axons (long nerve cell protrusions).

    It is therefore reasonable to assume that the microenvironment itself and especially the communication between Schwann cells and their adjacent axons, is a promising therapeutic target for Schwann cell-derived nerve sheath tumors. With this research proposal, we therefore aim to establish a novel and innovative approach in which we will use recombinant proteins to prevent schwannoma development by altering the interaction of Schwann cells and axons.

    Protein replacement therapies have been proven to be a valuable treatment for a number of rare monogenetic diseases (Gorzelany and de Souza, 2013). However, instead of replacing the protein merlin in order to treat schwannomas, we aim to replace the aforementioned axon surface protein Neuregulin 1, which is crucial for Schwann cell behavior and is considered safe as a result of phase 2 clinical trials for heart failure. In addition, we assume that replacing a protein outside of the cell is presumed to be easier than delivering an artificial protein into the cell's interior.

  • Dr. Lei Xu, Massachusetts General Hospital – Research,Combining immunotherapy and antiangiogenic therapy in NF2 schwannoma model
    Currently, there is no cure for Neurofibromatosis type II (NF2); clinical management focuses on regular monitoring and, if possible, treating problems as they arise. Surgery and radiotherapy involve risks that can often outweigh the benefits. The ability of systemic treatment with anti-angiogenic agents (bevacizumab) to improve hearing in patients with progressive vestibular schwannomas has stimulated interest in anti-angiogenic therapy. However, not all NF2 patients respond to bevacizumab and the hearing response is not durable. Thus, NF2 is a disease that needs new solutions. Our study explores a novel direction to combine anti-angiogenic treatment with immune therapy to achieve an enhanced and durable efficacy. Immune therapy is used to provoke the immune system to attack the tumor cells. The recent success of immune checkpoint inhibitors has demonstrated exciting and durable remissions across a spectrum of malignancies. However, as a benign tumor, little is known whether NF2 patients are immune suppressed or how the benign schwannomas respond to immune therapy in patients. Our exciting preliminary data shows that NF2 patients are in an immune suppressive state, and immune checkpoints are potential targets in NF2 vestibular schwannomas. Furthermore, we showed that anti-VEGF treatment "normalizes" the schwannoma vasculature and tumor microenvironment. It has been shown that the aberrant tumor vasculature and the resultant hostile tumor microenvironment are key obstacles to successful immunotherapies. Based on these, we propose to strategically target abnormal vasculature and immunosuppression simultaneously to boost the anti-tumor effect from each treatment. The proposed study will demonstrate if vascular normalization can enhance the anti-tumor efficacy of immune checkpoint inhibitors in schwannoma. If the data suggest that anti-angiogenic therapy plus immune checkpoint blockade is superior to either therapy alone, Dr. Plotkin, our collaborator at Massachusetts General Hospital, will use the results to design a clinical trial for NF2 patients using agents that are currently in development for human studies.

  • Dr. Steven Lewis Carroll, Medical University of South Carolina,Combinatorial Therapy with Receptor Tyrosine Kinase Inhibitors for Malignant Peripheral Nerve Sheath Tumors
    We know that NF1 mutation results in Ras hyperactivation in malignant peripheral nerve sheath tumors (MPNSTs). Unfortunately, so far it has not been possible to develop therapies that inhibit Ras in MPNSTs. This led us to consider the possibility that targeting the molecules that activate Ras in these tumors in the first place might be an alternative approach to treating MPNSTs. We thought it likely that members of a class of growth factor receptors known as receptor tyrosine kinases (RTKs) might be the Ras activators that we were looking for in NF1-associated MPNSTs. We identified 3 drugs that effectively inhibited MPNST proliferation and, to a lesser degree, survival: the pan-erbB inhibitor canertinib (CI-1033), the insulin-like growth factor 1 receptor (IGF1R) inhibitor picropodophyllin and lestaurtinib, which inhibits the trk family of RTKs, FLT3 and JAK2. We next asked whether these three drugs inhibited Ras activation. We found that two of them, canertinib and picropodophyllin, did markedly reduce Ras activation. Based on these preliminary studies, we propose that canertinib, picropodophyllin and/or lestaurtinib will effectively inhibit the proliferation and survival of MPNST cells by inhibiting key RTKs and that therapies combining canertinib with picropodophyllin or lestaurtinib will be superior to treatment with any of these agents individually. The funding that we are requesting will allow us to obtain three key pieces of information that we will need to get NIH or DOD funding: 1) a determination as to which of the multiple kinases targeted by canertinib and lestaurtinib are absolutely required for MPNST proliferation and survival; 2) information as to how commonly the kinases targeted by canertinib, lestaurtinib or picropodophyllin are expressed in surgically resected MPNSTs and human MPNST cell lines; and 3) "proof-of-principle" experiments demonstrating that therapy with canertinib, picropodophyllin or lestaurtinib is tolerated and effective against MPNSTs in mouse models. We will also obtain evidence as to whether treatments combining canertinib with picropodophyllin or canertinib with lestaurtinib are more effective than treatment with canertinib, picropodophyllin or lestaurtinib alone in mouse MPNST models.

  • Dr. Jeffrey Field, University of Pennsylvania,MPNST profiling and screening: an experiment in Research based Education
    One of the problems that NF patients fear most is the high risk of tumors. At present there are no drugs specifically approved for treating NF. We will screen drugs, both known and novel against NF tumor cell models, primarily cancer models. The known drugs will serve as a starting point for comparison with other screening efforts. We propose to do our screens in a novel way, by developing a course in drug screening. We will start with a small set of compounds, using simple screens, but build in complexity as we learn what works with the students. Our course will team a chemist with a biologist so compounds can be screened and modified. As far as my research into courses goes, this will be the first course in drug screening.

2014 DDI Awardees

  • Miriam Smith, PhD, University of Manchester , Treatment of Neurofibromatosis Type 2 (NF2) by Exon Skipping
  • Andrea McClatchey, PhD, Harvard Medical School, Preclinical Investigation of Centrosome Unclustering Drugs in NF2-mutant Schwannoma
  • David Largaespada, PhD, University of Wisconsin-Madison, Targeting Hyaluronic Acid for NF1-associated Tumors
  • Gregory Riggins, MD, PhD, Johns Hopkins University, Testing Combinations of FDA-approved Agents with and without Radiation Therapy in an NF2 Schwannoma Murine Model

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