Letter of Intent InstructionsTo have your Rediscovery Research Grant considered for the Patient Impact Initiative (PII), please complete this Letter of Intent form and e-mail it to Partnership for Cures along with a Principal Investigator (PI) Biosketch. We will review the Letter of Intent and contact you to complete a grant application if your project fits our Rediscovery Research™ model.

ELIGIBILITYThe Patient Impact Initiative is open to all researchers and clinicians at or on staff at academic medical centers and other research institutions that have agreed to become Partner Institutions in the Patient Impact Initiative. It is also open to invited researchers at other institutions.

PLEASE REVIEW THE DESCRIPTION BELOW OF THE RESEARCH WE ARE REQUESTING. The closer the research is to making a direct patient impact, the more likely it is to be highly ranked. Pilot or other clinical trials are ideal. Cost effectiveness is a key ranking criterion.

AREAS OF FOCUS: We accept proposals in any disease and for any Rediscovery Research therapy. We do have some committed funds for clinical trials in CLL ($30K/year for 2 years, to prolong remission), myelodysplastic syndrome (RARS variant, up to $100K/year for 2 years) and lung cancer ($30K/year for 2 years.) We also have funders interested, but not committed to, pediatric cancer and rare disease projects.

There is no fee to apply to the Patient Impact Initiative.

CHECKLISTPlease include:

Completed Letter of Intent Form below, including the grant title/description (400 word max) of you proposed research project

PI Biosketch or CV so your eligibility can be confirmed

PLEASE NOTE

Letters of Intent must be submitted electronically to PII-LOI@4cures.org Letters of Intent are due not later than March 2, 2012 at 9:00 pm Central

Time Required documents listed above must be submitted as a single Microsoft Word

Document file (any version.) Submit only the Letter of Intent Form and PI Biosketch. Do not include the rest of the information in this document.

The file should be named in the following format:

PII LOI Year-Month Institution First Name Last Name Project Title.doc

(Example - PII LOI 2012-1 UIC Bruce Bloom Repurposing Maddonic Acid for Rockitis.doc)

Patient Impact Initiative Letter of Intent FormPlease complete the following Principal Investigator and Project information:

First Name Last Name Degree(s) Dept/Division Academic Title Institution Street Address City State Country Postal Code Office Phone Mobile Phone E-Mail Address

Project type (Please check all that apply)

Lab Only Lab/Animal Trial Animal Trial

Lab/Human Samples Human Clinical Trial

Estimated project length in monthsEstimated project cost

Research Project Title:

Research Description (Please type here - Not more than 400 words describing the proposed research project. The 400 words do not have to fit on this page only-they can continue onto a separate page.)

If you have any questions, please contact:

Dr. Bruce E. Bloom, Ashoka Fellow 2010-2012President and Chief Science Officer, Partnership for Cures585-542-8737 or Bruce@4cures.org    

Rediscovery Research™ Description

The Patient Impact Initiative inspires scientists and clinicians (and interested parties outside of medicine) to create and complete pilot clinical trials and other Rediscovery Research to directly impact patients. This “Rediscovery Research” can impact patients by reusing, reconfiguring and combining already existing drugs and devices, modifying treatment protocols and testing clinical observations. These 1-3 year Rediscovery Research Projects can focus on any disease, use any therapy and impact any group of patients, as long as they meet the parameters of the Patient Impact Initiative, which are to create better near term treatment options, improve early diagnosis and lengthen disease remission reusing science and medicine that has already been discovered once.

What qualifies as Rediscovery Research?

The following are some examples of Rediscovery Research. It is likely that once the Patient Impact Initiative creates the incentive for Rediscovery Research, bright minds will find new ways to use reuse, combine and newly apply already available science and medicine to help patients.

1. repurposing an FDA approved drug or drug combinations to treat "off label" diseases 2. combining an older drug or a combination of older drugs with a newer drug to increase the

newer drug effectiveness3. combining a drug with a non-drug treatment option, such as radiation, to make the non-

drug treatment work better4. combining a non-drug treatment option with an available drug to make the drug work

better 5. testing combinations of available drugs that are not currently prescribed together but are

already used in one specific disease to see if the combination works better in that disease6. scientifically testing combinations of vitamins, supplements and botanicals, that would be

available to physicians and their patients, if efficacy can be proven7. in limited circumstances, human clinical testing of new compounds, in rare diseases for

which there is no current treatment, and there is strong likelihood of efficacy and accelerated approval

8. repurposing FDA approved devices to treat "off label" diseases 9. modifying current treatment protocols to make them work better and help more patients

for longer periods of time, such as modifying the time of day of drug administration, reducing drug doses while increasing the frequency of drug administration to reduce side effects, testing radically lower doses of effective medicines that patients refuse because of side effects

10. scientifically testing clinical observations or sound clinical ideas, including those from integrative medicine or from other parts of the world

Examples of Rediscovery Research

· Repurposing of thalidomide for multiple myeloma, then other blood cancers, other cancers, and non-oncologic diseases, and the development of Revlimid (Repurposing Example 1 from above)

· Testing the addition of NK cells to autologous stem cell transplants to improve the remission rate in non-Hodgkin’s lymphoma (Repurposing Example 9 from above)

· Combining an old malaria drug with a new kinase inhibitor to help the kinase inhibitor work for more lung cancer patients for a longer period of time (Repurposing Example 2 from above)

· Creating life saving treatments for children with familial dysautonomia by screening and then proving that specific vitamins and botanical compounds increased the overall production of a critical protein (Repurposing Example 6 from above)

· Repurposing a device originally developed to help the blind “see” to significantly improve functional performance in multiple sclerosis and traumatic brain injury patients (Repurposing Example 8 from above)

· Repurposing a laser ablation device originally used to treat breast cancer to treat prostate cancer patients with a much low incidence of side effects such as incontinence and impotence (Repurposing Example 8 from above)

· Repurposing the pain medication buprenorphine for the interruption and maintenance of heroin and other opioid addictions (Repurposing Example 1 from above)

· Repositioning the anti-Parkinsonian drug Requip for the treatment of both Restless Legs Syndrome and SSRI-induced sexual dysfunction (Repurposing Example 1 from above)

· Repositioning anti-epileptics gabapentin and pregabalin for treating anxiety disorders and neuropathic pain. (Repurposing Example 1 from above)

· Proving that Hatha Yoga breathing and relaxation can be as effective a treatment for Generalized Anxiety Disorder as drugs or counseling (Repurposing Example 10 from above)

Why Rediscovery Research?

There are thousands of potential treatments waiting to be rediscovered in the medicine and science that already exists. Of the top 50 selling pharmaceuticals in 2004, 84% have had additional indications approved since their initial US licensure (http://www.msi.co.uk/drug-repurposing). This type of Rediscovery Research provides

· low research costs and fast delivery of “new” effective treatments to patients by leveraging knowledge, resources and regulatory approvals already paid for through past research and clinical experience

· treatments that typically use low cost drugs and devices with known safety profiles, following slightly modified treatment protocols with which clinicians are already familiar

· significantly reduced healthcare costs created in a fraction of the time and expense

The Patient Impact Initiative Rediscovery Research will take place at academic research Partner Institutions, biotechs, pharmaceutical companies and large clinical practices. Administration will be centrally provided by the staff of the Partnership for Cures. Project reviews will be conducted by independent volunteer clinicians, scientists and lay reviewers using an electronic interface. Rediscovery Research Projects must be designed to make a direct impact on patients in 1-3 years and can cost $10,000-$100,000 per year, with an emphasis on funding frugal, cost-effective grants that impact patients.

What is the Patient Impact Initiative Grant Process?

The Patient Impact Initiative has a two-step Grant Process. Step one is the completion and submission of a very short Letter of Intent (LOI) form. This enables our scientific and lay reviewers to determine if the project is likely to meet our Patient Impact Initiative parameters.

You will be informed within 2 weeks of your LOI submission whether or not to submit a full Grant Proposal. If you are invited to submit a full proposal, we will send you a form to complete that will include:

· A description of the proposed research (1600 word max)· A budget and timeline· A description of how/when your Rediscovery Research idea will impact patients · The NIH Biosketch of the PI and full PI contact information· Names of three scientists and/or clinicians you feel are qualified to review your project

who have no conflict of interest

Grants will be reviewed and ranked by scientific and lay reviewers. The closer the research is to making a direct patient impact, the more likely it is to be highly ranked. Pilot or other clinical trials are ideal. Cost effectiveness is also a key ranking criterion.

All LOIs and Grant Proposals should be sent as Microsoft Word documents via e-mail. Instructions are included on the LOI and Grant Proposal forms.

Mission: The mission of the Patient Impact Initiative is to secure funds to improve healthcare outcomes and reduce patient healthcare costs worldwide by financing, facilitating, and publicizing Rediscovery Research solutions that repurpose drugs, test clinical observations, and modify treatment protocols.

Vision: To create and manage a global collaboration of philanthropists, disease specific non-profits, research institutions, researchers, clinicians, industry, media and the lay public that raises and deploys funds to drive the development Rediscovery Research solutions to patients that quickly improve quality and length of life.

APPLICATIONGRANTEE INFORMATION

Sponsoring Institution Name Peotone State University

Grantee's First Name BruceGrantee's Last Name BloomLink to Grantee’s research/profile website

http://www.4cures.org/home/meet_the_staff

Grantee's Institutional Address, line 1 70 West Madison StreetAddress, line 2 Suite 1500Address, line 3City ChicagoState ILZip code 60602Grantee’s Email address bruce@4cures.orgHome phone 847-948-7004Office phone 312-696-1366Cell phone 847-529-6888Fax number 312-263-0939Current academic title and degrees Assistant Professor, MD, JDCurrent academic department(s) Clinical Research

RESEARCH PROPOSALTitle of research proposal Pilot human clinical trial to determine the effectiveness of a three

different olfactory trained service dogs in the early detection of lung cancer

Estimated total budget $28,000Estimated length of research (in months)

18 months (2 months for IRB approval and dog training and validation, 12 months for enrollment of subjects and collection of data, 1 month for data processing and statistical analysis, 3 months for preparation, submission and acceptance of manuscript)

Indicate whether this is lab research, animal study, human clinical trial, other (if other, describe)

Human clinical trial

Number of human subjects (If applicable)

300

Age range of human subjects (if applicable)

21-49

Primary disease(s) research could impact

Lung cancer

Secondary disease(s) research could impact

Other cancers that have metastasized to the lung; TB, other inflammatory lung diseases

Key words (as many as possible) (Examples: stem cell, gene therapy, sRNA, diagnostic, prevention, treatment, consortium, anti-viral, botanical, translational, multiple sclerosis, cancer, pediatric, geriatric,

Service dog, expired breath, lung cancer, spiral CT, early detection, smokers, smoking, x-ray, screening

Patient Impact Initiative Rediscovery Research Proposal

etc.)

INSTITUTIONAL OFFICER CONTACT INFORMATIONInstitutional Officer Contact Name Jerry ParisContact Title Department ChairAddress, line 1 70 West Madison StreetAddress, line 2 Suite 1500Address, line 3City ChicagoState ILZip code 60602Email address bruce@4cures.orgOffice phone 312-696-1368Fax number 312-263-0939

PUBLICATION AND DISCLOSUREPublication-has there been any public disclosure of this idea, either by you or some other party (Yes/No/I don’t know?) If Yes, when and by who?

Yes, see http://www.pinestreetfoundation.org/articles/ICT.pdf

Disclosure- Have you disclosed this concept to your institution, and, if not, is there a plan for disclosing

Yes

CONTACT INFORMATION FOR SCIENTISTS QUALIFIED TO REVIEW YOUR GRANT (AFTER THEY SIGN A NON-DISCLOSURE AGREEMENT.) THEY MUST BE FROM OUTSIDE OF YOUR INSTITUTION AND NOT INVOLVED IN ANY OF YOUR RESEARCH.

Potential Reviewer #1Name Steve BrownInstitution University of ChicagoEmail address SBrown@uchicago.eduOffice phone 312-555-1212

Potential Reviewer #2Name Doug GeorgeInstitution University of Southern CaliforniaEmail address DougG@uic.eduOffice phone 773-555-1212

Potential Reviewer #3Name Jeff SmithInstitution Rush University Medical CenterEmail address JSmith@rush.eduOffice phone 708-555-1212

Now Please Complete Grant Proposal Information Below

Please type in 11 point Arial font-Thank you!

Principal Investigator and co-investigators, including affiliations

PI-Bruce Bloom, DDS, JD, Chief of Pulmonary Oncology, Peotone State University, Peotone ,ILCoordinator-Kathy Knorr, MS, BSN, Peotone State University, Peotone ,ILDog Safety-John Smith, DVM, PhD, Head of Animal Sciences, Floosmor Veterinary CollegeDog-Trainer-Ron Pace, Owner, Dog Training International, Chicago, ILDog Handlers-Graduate students John Jones, Tom Brown, Laura White from Floosmor Veterinary CollegeStatistician-Monty Pythagoras, University of Chicago

Narrative Title of Proposal

A pilot human clinical trial to determine the effectiveness of olfactory trained service dogs in the early detection of lung cancer by screening smokers with a cough of 30+ days who have been seen by an MD and referred for a spiral CT scan

Rationale: What is the clinical problem that creates a need for this research

Identify the challenge and opportunity

(No more than 200 words)

There are several very small studies and many anecdotal observations that the superior olfactory ability of dogs can be used to detect cancer and other disease states. Ron Pace at DTI has now trained over 30 service dogs to detect blood glucose changes in exhaled breath, and data collected using his dogs has shown a 99.5% accuracy at determining blood glucose below 80 or over 180. The service training has now been extended to lung cancer, and his trained dogs are over 98% accurate in lab tests distinguishing breath samples from smokers with lung cancer and without lung cancer. There is no cost effective screening for lung cancer at this time, and no machine is as sensitive as a dog’s nose. Testing three different dogs will help us to determine whether this could be a widely used method of screening.

Goals, Aims and/or Objectives (No more than 300 words)

This study will test if olfactory trained service dog screening is sensitive and reliable for the early detection of lung cancer in smokers with a cough. Our goal is to screen 300 subjects in a 12 month period of time and correlate the three dog screening data with the CT scan and biopsy data. Long term 2 and 5 year follow-up of subjects will also be done in order to determine if the dogs detected lung cancer not detected by CT scan. Aim 1-receive IRB approval to add the dog screening to an IRB approved projectAim 2-to train 3 service dogs to detect lung cancer from test samples of smokers who have and have not been diagnosed with lung cancerAim 3-to screen at least 10 subjects per day over a 36 week period at the weekly screening day at the Peotone State University pulmonary clinic. That clinic sees, on average, 60 smokers with persistent cough per screening day. The three dogs will each be in a separate room for screening, and the dog handlers will be rotated among the dogs at different weeks.Aim 4-to correlate the data with the results of the spiral CT scans and any f/u biopsies to determine who well each individual dog did in early detection, and how the dogs compared to each other and to their lab successesAim 5-to publish the data in the Journal of Pulmonary Oncology

Background, basic study design and narrative (No more than 1600 words and 4 figures/ diagrams, in no more than 3 total pages. Please write on a separate document and attach as a Microsoft Word Document to the proposal.)

Please write on a separate document and attach as a Microsoft Word document to the proposal.

PLEASE NOTE-AN EXAMPLE OF THIS IS NOT ATTACHED

Suggested formatA-Background and preliminary studiesB-Study DesignC-Evaluation of resultsD-Statistical methods, if any

Please type in 11 point Arial font and use margins no narrower than 0.5”

Thank you!Potential clinical impact and what would be the potential next steps (No more than 300 words)

There is no accurate and cost effective method of screening for the early detection of lung cancer in smokers with a persistent cough. If the data show that olfactory trained service dog screening is an accurate lung cancer screening tool, we will

1) Begin using the service dog screening at Peotone State University on a regular basis

2) Secure funds for training service dogs to be used in three different institutions to validate these early findings within 2 years

3) Begin an aggressive dog and physician/nurse or tech handler training program at Peotone State University

4) Secure funds to do a wider screening of non-smokers with persistent cough and smokers with no symptoms to see if dog screening is reliable and verifiable in those groups

5) Develop a service dog olfactory training program and certification program from dog trainers so that more dogs can be appropriately trained using the Dog Training International techniques. Ron Pace has agreed to create and provide this training for no charge.

6) Begin working with the government and other payers to secure health care coverage for olfactory trained service dog screening visits, which we have calculated to cost no more than $3.00 per visit.

Publication: Where and how do you expect to present the data you gather from this research?

We will publish this in the Journal of Pulmonary Oncology. We also expect to get significant service dog trade publication exposure, as well as national press coverage. We also expect to publish an editorial in the Journal of Applied Veterinary Medicine, and have ample opportunity to present the results of this research at various meetings of pulmonologist, veterinarians and dog trainers.

Narrative budget Please note: There will be no indirect costs allowed for these Patient Impact Initiative Rediscovery Research grants.  However, administrative personnel costs of up to 10% of the budget or 10% total effort of named administrators, whichever is less, can be added to the direct costs budget but only if specifically justified.  

Most Clinical Projects will not be approved with PI salaries, and overall cost-effectiveness is a critical criterion in our decision-making process. Be as frugal as you can and still accomplish your goals. We are mostly interested in projects that show clinically significant difference between control and test groups, or where a test group shows clinically significant differences from the normal course of the disease where there is no control group.

Narrative budget small description plus a listingA-personnelB-animalsC-patient costsD-core facilities and servicesE-suppliesF-other(Approximately 300 words plus budget figures )

Peotone State University just received a 18 months federal grant to screen 300 smokers with a history of persistent cough of 30-60 days using spiral CT scans and follow-up biopsies, when necessary. All costs associated with enrollment and management of the subjects in this study will be covered by the federal grant. Only the costs associated with training and managing the dogs, IRB approval, statistical evaluation and publication/presentation are required for this project. The training of the dogs takes only about a month, and they can screen hundreds of subjects per day for less than $0.50 per subject! The PI and collaborators are receiving no support for this project.

$28,000 Overall Budget$14,350 A-personnel-$8,350 for Ron Pace dog training, $2000 per grad student stipend for dog handler training and being present at the Saturday research dates$10,950 B-animals-training, housing, vet care, food for 12 months equals $10/dog/day X 365$0 C-patient costs-all covered by other grants$1200 D-core facilities and services-data processing, videography, manuscript submission support$1500 E-supplies-purchase of three different 2-3 year old dogs of different breeds for training$0 F-other

Conflicts-Please list any conflicts or potential conflicts that could arise or are clearly present as a result of this research

Ron Pace also trains for-profit blood glucose olfactory service dogs for type 1 diabetics, and will begin to train dogs to detect lung cancer, so any notoriety from this project may have a positive (or negative) financial impact for him.

We have applied for funds for this research to the LUNGevity Foundation and to the Peotone Rotary Club, but have not received a response.

We are aware of no other conflicts.Supporting literature-You are welcome to provide citations and short explanations to as many as three publications that provide a scientific and/or clinical foundation for why this work is important and can make a patient impact

Paper 1 shows that there is anecdotal support for the reliable and verifiable use of olfactory trained service dogs for lung cancer screening.

Paper 2 details the successful training methods of Ron Pace and Dog Training International for olfactory trained blood glucose monitoring service dogs.

Paper 3 describes successes reduced mortality, morbidity and healthcare costs associated with the use of olfactory trained blood glucose monitoring service dogs over a ten year period of time.

Please Sign Below

The PI and the institution are willing and able to support all aspects of these studies, including IRB and other approvals, and the PI is a person who is eligible to receive Federal Grants.

PI Signature

Date 3-21-2012

Institutional Officer (listed above) Signature

Date 3-22-2012

Send completed application and grant proposal as a Microsoft Word document (any version) via e-mail to:

PII-Grant@4cures.orgDr. Bruce E. Bloom, President and Chief Science Officer, Partnership for Cures 312-696-1366

Grant Proposals are due no later than 9:00 p.m. Central time on Thursday April 12, 2012

Please label as follows:2012 PII GPP Institution Firstname Lastname Research title.doc

(e.g 2012 PII GPP UIC Bruce Bloom Silencic Acid for Babbloritis.doc)

APPLICATIONGRANTEE INFORMATION

Sponsoring Institution NameGrantee's First NameGrantee's Last NameLink to Grantee’s research/profile websiteGrantee's Institutional Address, line 1Address, line 2Address, line 3CityStateZip codeGrantee’s Email addressHome phoneOffice phoneCell phoneFax numberCurrent academic title and degreesCurrent academic department(s)

RESEARCH PROPOSALTitle of research proposalEstimated total budgetEstimated length of research (in months)Indicate whether this is lab research, animal study, human clinical trial, other (if other, describe)Number of human subjects (If applicable)Age range of human subjects (if applicable)Primary disease(s) research could impactSecondary disease(s) research could impactKey words (as many as possible) (Examples: stem cell, gene therapy, sRNA, diagnostic, prevention, treatment, consortium, anti-viral, botanical, translational, multiple sclerosis, cancer, pediatric, geriatric, etc.)

Patient Impact Initiative Rediscovery Research Proposal

INSTITUTIONAL OFFICER CONTACT INFORMATIONInstitutional Officer Contact NameContact TitleAddress, line 1Address, line 2Address, line 3CityStateZip codeEmail addressOffice phoneFax number

PUBLICATION AND DISCLOSUREPublication-has there been any public disclosure of this idea, either by you or some other party (Yes/No/I don’t know?) If Yes, when and by who?Disclosure- Have you disclosed this concept to your institution, and, if not, is there a plan for disclosing

CONTACT INFORMATION FOR SCIENTISTS QUALIFIED TO REVIEW YOUR GRANT (AFTER THEY SIGN A NON-DISCLOSURE AGREEMENT.) THEY MUST BE FROM OUTSIDE OF YOUR INSTITUTION AND NOT INVOLVED IN ANY OF YOUR RESEARCH.

Potential Reviewer #1NameInstitutionEmail addressOffice phone

Potential Reviewer #2NameInstitutionEmail addressOffice phone

Potential Reviewer #3NameInstitutionEmail addressOffice phone

Now Please Complete Grant Pre-Proposal Information Below

GRANT PROPOSALPlease type in 11 point Arial font-Thank you!

Principal Investigator and co-investigators, including affiliations

Narrative Title of Proposal

Rationale: What is the clinical problem that creates a need for this research

Identify the challenge and opportunity

(No more than 200 words)Goals, Aims and/or Objectives (No more than 300 words)

Background, basic study design and narrative (No more than 1600 words and 4 figures/ diagrams, in no more than 3 total pages. Please write on a separate document and attach as a .pdf to the proposal.)

Please write on a separate document and attach as a .pdf to the proposal.

Suggested formatA-Background and preliminary studiesB-Study DesignC-Evaluation of resultsD-Statistical methods, if any

Please type in 11 point Arial font and use margins no narrower than 0.5”

Thank you!

Potential clinical impact and what would be the potential next steps (No more than 300 words)

Publication: Where and how do you expect to present the data you gather from this research?Narrative budget Please note: There will be no indirect costs allowed for these Patient Impact Initiative

Rediscovery Research grants.  However, administrative personnel costs of up to 10% of the budget or 10% total effort of named administrators, whichever is less, can be added to the direct costs budget but only if specifically justified.  Well-justified budgets are

important, insofar as cost-effectiveness will be used as a key scoring criterion.

Narrative budget small description plus a listing

A-personnelB-animalsC-patient costsD-core facilities and servicesE-suppliesF-other(Approximately 300 words-ok to provide some narrative)

Conflicts-Please list any conflicts or potential conflicts that could arise or are clearly present as a result of this research

Supporting literature-You are welcome to provide citations and short explanations to as many as three publications that provide a scientific and/or clinical foundation for why this work is important and can make a patient impact

Please Sign Below

The PI and the institution are willing and able to support all aspects of these studies, including IRB and other approvals, and the PI is a person who is eligible to receive Federal Grants.

PI Signature __________________________

Date _____________

Institutional Officer (listed above) Signature ______________________

Date _____________

Send completed Grant Proposals via e-mail to:

PII-Grant@4cures.orgDr. Bruce E. Bloom, President and Chief Science Officer, Partnership for Cures 312-696-1366

Grant Proposals are due no later than 9:00 p.m. Central time on Thursday April 12, 2012

Please label as follows:PII Grant Year-Month Institution First Name Last Name Research Title.doc

(e.g PII GPP 2012-3 UIC Bruce Bloom Silencic Acid for Babbloritis.doc)