Nevada Institute of Personalized Medicine at UNLV

UNIVERSITY OF NEVADA, LAS VEGAS NEVADA INSTITUTE OF PERSONALIZED MEDICINE Nevada Institute of Personalized Medicine at UNLV Quarterly Progress Report Reporting Period: April 1st to June 31th, 2016 August 1, 2016

Table of Contents Project Purpose... 0 1. Problem NIPM is trying to solve... 0 2. Expected impact... 0 Section I: NIPM Progress... 1 Section II: Performance... 5 Table 3: Progress toward Metrics... 5 a. Dashboard details for reporting external faculty hired... 6 b. Dashboard details for reporting grants and amount of research funding received... 6 c. Dashboard details for reporting number of student internships... 7 d. Dashboard details for reporting number of patent applications... 7 Section III: Budget... 8 Section IV: Weekly/Monthly Logs of NIPM Progress for Reporting Quarter... 10 Section V: Appendix... 13 Appendix 1 Sales Pipeline... 13 Appendix 2 Scorecard Supporting Documentation... 14 Page 1

Project Purpose 1. Problem NIPM is trying to solve Approximately 1 in 10 suffer from a genetic disorder, yet Nevada has almost no in- state infrastructure to diagnose and treat affected patients. This health disparity in our state negatively impacts the health and well- being of many Nevadans, as well as our economy by the continued export of genetic healthcare services and related revenues to other states. 2. Expected impact The Nevada Institute of Personalized Medicine and an affiliated enterprise will help regional healthcare partners utilize and deliver clinical genetics services and educate a clinical genetics workforce for Nevadans. During the funding period starting July 1, 2015, our major long- term goal is to build a clinical genomics trial entity to provide services for Nevadans. The clinical genomics trial entity will engage Nevada healthcare providers in personalized medicine. To achieve this goal, NIPM has identified a set of stepwise intermediary milestones (Figure 1). Detailed justification for these goals is provided in the separate Knowledge Fund application document. Note that some milestones were adjusted in this progress report. The milestones in Figure 1 have been given numbers for easier reporting (Table 1).

Table 1: Milestones Milestone number Milestone 1 Milestone 2 Milestone 3 Milestone 4 Milestone 5 Milestone 6 Milestone 7 Milestone 8 Milestone 9 Milestone 10 Milestone 11 Milestone 12 Milestone 13 Milestone 14 Milestone 15 Description IRB approval Implement a computer system Set up NGS pipeline Set up personalized medicine database Conduct SOAPS Trial Establish Omics core Validate Omics core Genetics oriented business plan Genetics- oriented commercial agreement GWAS trial involvement COBRE grant Clinical Genetics services UNLV School of Medicine Pathology CLIA Sequencing Lab Clinical genomics trial service Section I: NIPM Progress During the reporting quarter, NIPM has made significant progress toward meeting proposed metrics. Major accomplishments for the current reporting period include: Major Accomplishment 1: Genome Sequencing Core (Milestone 6). We have purchased all of the equipment needed for the genome sequencing core, have started to setup the core lab, and had the NextSeq installed and ran our first Sequencing reactions. We have configured the new file server to store the genomes and NIPM database. We are negotiating with combining our technology with the existing core and have also started a search for NGS sequencing technician. Major Accomplishment 2: Faculty Searches (Milestones 3, 4, 5, 11). NIPM conduced two searches for faculty to help run the genome sequencing core. We offered the job for the professorship that would be involved in NGS sequencing to Dr. Peng Li from NIH, but he rejected the offer because we could not identify a job for his wife that worked in chemical engineering. We offered the NGS bioinformatics job to Dr. Son Pham (Scripps Research Institute) and he accepted the offer. However, we are having issues with his visa and will need to wait a little longer to see if he can be hired. Major Accomplishment 3: Business Development Officer Search (all milestones). Page 1

NIPM worked with the UNLV Office of Economic Development to search for a new Business Development Officer. The period was spent vetting and interviewing candidates, and a new hire was on- site just after the end of Q2, 2016. James Timmins (Madison, Wisconsin,) was offered the job and accepted and will arrive July 5, 2016. Dr. Schiller has managed this role for the period, but is transitioning these duties. Commercial planning, opportunities, and proposals are expected to accelerate during the next reporting period. Major Accomplishment 4: NIPM Medical Genetics Clinic (Milestones 1, 5, 13-15). NIPM established a partnership with the UNLV School of Medicine and Grant a Gift Autism Foundation to set up a Medical Genetics Clinic as part of an autism clinic that will begin in the first part of Q3 2016. Dr. Nasiak will be the Clinical Geneticist on staff. We had minor delays, but the clinic will open July 5, 2016. 1. Commercialization / Partnering Industry partnerships, research collaborations, and IP licensing remain a priority for NIPM, although this activity continued to be slow during the reporting quarter given the lack of a NIPM Business Development Officer to guide these efforts. Despite this limitation, a total of five new contacts were made with companies and individuals regarding partnerships or IP licensing opportunities this quarter (see appendix). NIPM will continue to cultivate alliances with external colleagues and industry partners working in personalized medicine through: (1) direct communication; (2) industry outreach; (3) establishing formal and informal relationships with industry and academic partners; (4) engaging scientists in the NIPM seminar series; and (5) hosting annual events. 2. Intellectual property During the reporting quarter, a significant invention disclosure was submitted to the UNLV Office of Economic Development by Dr. Schiller. This application builds and broadens the previous Chimeric Minimotif Decoy technology, to be more applied to Personalized Medicine, including a mechanism to discover single- cells with optimized biological traits, which further can have significant commercial value to existing products and serve as a vehicle to create new products. Personalized Medicine will benefit from this new application, as it provides a way to create custom personalized medicines and provides a means to interpret variants of unknown significance, one of the major barriers to personalized medicine. At the end of this quarter, this disclosure remains in the filing stage and pre- proof of concept,. The above filing replaces the HIV filing from 2015, leaving still a total of four patent application families, based on innovations developed by NIPM Executive Director Dr. Martin Schiller in active prosecution (see Table 2). The new Business Officer will review, with current OED and legal counsel, the status and commercial promise of all filings to date in the next reporting period. Page 2

Table 2 NIPM Intellectual Property Internal(ID Inventor Title Patent/Applciation(No. Change(since(last(report 2013=001 Martin(Schiller Genome(Surgery(with(Paired,(Permeant(Endonuclease( 13/937,860 PCT(applciation(converted(to(EPO(applciation Construct EPO=13816139.3 US(Applciation(13/937,944(was(abandoned 2010=003 Martin(Schiller Methods(and(Systems(for(Information(Search 14/328,316 PCT/US2015/039131 Reporting(filing(of(PCT 2014=034 Martin(Schiller Methods(and(compostions(for(screening(molecular( funcitons(compursing(chimeric(minimotifs PCT/US2015/056247 Non=provisional((PCT)(application(filed 2015=032 Martin(Schiller Compositions(Comprising(Talens(And(Methods(of(Treating( 62/140,048 HIV( 62/265,232 2nd(provisional(patent(filed 3. Programmatic & project changes We have no programmatic changes to report here, but as we complete our Business plan next quarter expect minor changes in the next progress report. 4. Looking forward The relevance of each milestone to the two major goals is in Figure 1. The anticipated progress on each milestone is listed below. Milestone 1. IRB approval Additional changes were made to the IRB protocol and resubmitted. NIPM expected our IRB protocol to be approved this quarter, however, this is taking the IRB longer than expected we are working with the board and hopeful for an approval next quarter. We still continue to collaborate with the PeopleSeq project. Milestone 2. Implement a computer system The new FAT node of our computer systems was configured and is in use with NIPM faculty. A working group has started identifying NIPM requirements, reduces these to computer requirements, and then designing the build out of the NIPM computer system. Milestone 3. Set up NGS pipeline The necessary software is installed and running on the server and additional testing and optimization of the software are in process. WE will look for build our system and enhance these capabilities Milestone 4. Set up Personalized Medicine database The necessary tools for setting up an OrientDB database are available but there is a concern regarding the upload performance of the technology. Alternative technologies are being tested on the server as well as alternative configurations. NIPM has offered Dr. Son Pham an Assistant Professor position and he has accepted. He is an expert on algorithms and databases and will help oversee the database when he arrives. Milestone 5. Conduct SOAPS trial NIPM is waiting for IRB approval and will likely start this milestone in Q3 2016. Page 3

Milestone 6. Establish Omics core Now that the equipment is in place and installed, NIPM will work on a model for a staff member to prepare libraries and run the sequencing machine. We have created a technician position and plan to hire a ½ time technician using monies returned from NIPM grants. The Business Development Officer and Dr. Schiller are talking with Illumina about expanding the sequencing efforts and considering further UNLV resources (Genomics Core) to maximize NIPM s strategic opportunities. NIPM also applied for a grant with the Lou Ruvo Center for Brain health to hire a staff member and purchase Genotyping equipment. We expect to hear about this partnership this August. Milestone 7. Validate Omics core NIPM does not plan to start this yet. Milestone 8. Genetics- oriented business plan This milestone has been delayed and altered. NIPM ultimately decided that Athletigen was not the right partner to go forward with. We are considering refocusing this effort, perhaps on using genetics to increase ROI for health insurance plans. This will be explored with our new BDO. We plan to complete a business plan with the new BDO. See Milestone 10. Milestone 9. Genetics- oriented commercial agreement NIPM hired a new Business Development Officer this quarter. Milestone 10. GWAS trial involvement Milestone 11. COBRE grant NIPM completed this grant application and submitted it to NIH during Q1. NIPM anticipates a decision in the early Summer of 2016, possible resubmission next January, and funding in the Fall of 2017. Milestone 12. Clinical Genetics Services Efforts to begin clinical services have been under way to address the need of our mission goal of delivering medical care to individuals who are in need. This includes arrangements for location, addressing scheduling, purchasing of needed equipment and handling the details of billing. Initial plans were for beginning clinical services in April 2016, however a delay ensued outside of NIPM s control, and instead July 5 2016 is the opening of our services. We plan to see over 100 patients next quarter. Milestone 13-15 Page 4

Section II: Performance Table 3: Progress toward Metrics Nevada&Ins*tute&of&Personalized&Medicine&(NIPM)& Progress&Dashboard& KNOWLEDGE&FUND& GOED&Requested&Metrics& Current&Result&/&YearFend&Target&& To&6/30/15& By&3/31/16& By& 12/30/17& Number%of%Companies%that%moved%to%Nevada%as%a%result% of%nipm%kf%project% 0/0% %0%/%0% %0%/%0% Number%of%startBups% 0/0% %0%/%0% %0%/%1% Number%of%jobs%created% 0/0% %0%/%0% %0%/%0% Intellectual%property%licenses%/%opCons%% 0/0 A % 0/0 B % 0%/%0 A % 0%/%1 B % %0%/%1 A % 0%/%1 B % Intellectual%Property%Revenue%Received%by%University% 0/0% %0%/%$0% %0%/%$25k% Amount%of%research%grants%awarded%to%%(and%received)% the%nipm%research%teams%and%faculty C % Amount%of%research%funding%received%by%NIPM%research% team%from%industry%of%public%sector%agencies D% Number%of%sponsored%research%contracts%executed%on% behalf%of%nipm%research%team% $1M/ $500K% 0%/%$0K% 0/0% %$0K%/% $3.3M% 0%/%$205K% 0%/%0% %0%/%$3.3M% %0%/%$205K% %0%/%0% Number%of%patent%applicaCons%filed% %0/0% %0%/%2% %0%/%2% Number%of%issued%patents% %0/0% %0%/%0% %0%/%0% Number%of%students%placed%with%companies%%% 0/0% 0%/%0% 0%/%0% Number%of%external%faculty%hired% 3/3% 4%/%3% 4%/%3% Amount/value%of%giMs/donaCon%received%by%UNLV%in% support%of%nipm% $25K%/ 200K% $28K%/% $200K% $28K%%/% $200K% Total%number%of%student%internships%% 0/0% 2%/%0% 2%/%0% A. Number%of%IP%licenses% B. Number%of%opCons% C. Excludes%sponsored%research%and%KF%funding% D. This%category%also%inclused%clinical%reventue% Note%that%the%To%6/30/15%column%if%for%phase%I%of%this%project,%The%other%columns%are%for%phase%II% % n/a%or%target%of% Color&Key& zero% Too%early%to%tell% Goal%not%met% Close%to%achieving% goal% Goal%achieved% Page 5

Project Scorecard Narrative For each detail category, all progress for Q1 2016 is summarized. a. Dashboard details for reporting external faculty hired NIPM needs to hire experts in many different areas to achieve its two goals. Some of the regular faculty receive direct support from GOED (Martin R. Schiller, executive director and professor; Qing Wu, associate professor; Xiangning Chen, professor; Jingchun Chen, assistant professor; and Michael Nasiak, professor). These faculty are reported as the four hires on the dashboard Table 3 (executive director excluded). Two other regular faculty spend the majority of their research effort working with NIPM and have been approved as regular faculty (Mira Han, assistant professor and Justin Zhan, associate professor). One other Assistant Professor (Son Pham) is hired, but has not started yet. Table 3: Grant awards to NIPM regular faculty (April 1, 2014 to June 31, 2016) Proposal # PI Name Project Title Total 70114364 Schiller, Martin HIV Toolbox, An Interactive, Visual and Customizable HIV $331,875 Protein Ontology 99314578 Schiller, Martin A Novel High-Throughput Functional Screen Based Upon $222,000 Chimeric Minimotif Decoys 99314578 Schiller, Martin A Novel High-Throughput Functional Screen Based Upon $180,000 Chimeric Minimotif Decoys transferring Chen, Xiangning Understanding the genetic architecture of schizophrenia $450,000 in the Chinese population transferring Chen, Xiangning; Mapping the Genetic architecture of complex disease via $120,000 subcontract RNA-seq and GWAS data Jingchun Chen Genetic relationship between schizophrenia and $25,000 autoimmune disorders Total- GOED-funded faculty $1,372,871 awarded Han, Mira Transposable element silencing in human somatic cells. $353,244 Total NIPM regular faculty $1,726,115 For reporting, NIPM only reports metrics for GOED- funded faculty in the dashboard, but provides information for other categories where it is relevant. For example, it does not make sense for us to leave out Mira Han because she is located with NIPM faculty, works with NIPM daily, and is an essential person in the COBRE grant application and other milestones. b. Dashboard details for reporting grants and amount of research funding received Research funding is needed to leverage GOED dollars to hire the personnel needed to achieve Goal 1. For example, NIPM needs a postdoctoral fellow to analyze genome sequence data of participants in the clinical trial, a necessary capability in the proposed clinical service. Research funding is also needed, as NIH does not award large programmatic grants to teams that have not demonstrated previous consistent funding. Page 6

The number of grants received was not a metric in the original proposal. NIPM faculty receiving salary from GOED previously received four research grants for ~$1.1 M (Table 3). Two of these grants were to Dr. Xiangning Chen, and transferred or being transferred from Virginia Commonwealth University. These are not included in the reported metric for Q1 2016. Hiring a faculty member that brings in their own personalized medicine grants is a good way to leverage GOED funds. During this quarter NIPM received two additional awards to Drs. Jingchun Chen and Martin Schiller totaling $210,000 (table 3). c. Dashboard details for reporting number of student internships Trainees are critical for performing the work needed for goals 1 and 2, as well as providing trained individuals for the workforce. NIPM is reporting 0 trainees supported by GOED funding. However, many students in NIPM are working on NIPM projects. There are four graduate students working under NIPM regulation faculty (Drs. Schiller, Han, and Wu). One of these received a stipend from GOED faculty startup funds. Furthermore, Drs. Schiller, Wu, and Han have more than 20 undergraduate students being trained. Many of these are working on parts of goals 1 and 2. We also have two Postdoctoral Fellow Internships, one in the Schiller Lab and one in the X. Chen lab. d. Dashboard details for reporting number of patent applications A total of five patent applications / families, based on three innovations developed by NIPM regular faculty receiving GOED funding, remain in active prosecution (Table 1). However, NIPM reports none for the dashboard metric because all of these projects, at least in part, had their origins prior to the appointment of Dr. Schiller as executive director of NIPM. NIPM does not report this on the dashboard as it does not meet the criteria for the GOED reporting metric. A coversheet has been filed from a new application on technology developed in the Schiller lab. Page 7

Section III: Budget The Institute recognized expenditures of $446,119 during the reporting quarter. In all categories, total expenditures recognized were at or below estimates for the quarter. Detailed NIPM expenditure information is provided in Table 4: Table 4: NIPM Expenditures Category Total Budget Expenditures Inception to Date July 1, 2015 June 31, 2016 Expenditures Current Period April 1- June 31, 2016 Salary $1,025,116 $640,206 $158,7262 Fringe Benefits 465,800 $145,873 $34,474 Graduate Students 80,000 0 0 Equipment $389,885 $277,976 $49,821 Travel $30,000 $3,783 $1,524 Operations $93,440 $26,694 $11,619 Graduate Tuition $15,760 0 ($1,584) Faculty Startup $114,119 33,740 Other operating $90,000 0 0 Total $ 2,190,000 $1,525,677 $446,119 Detailed income information is provided in Table 5. Table 5: NIPM Income NIPM Income For Reporting Period April 1 June 31, 2016 1Estimate Income Income (Year 1) Inception to Date Current Period July 1, 2015 July 1, 2015 June 31, April 1- June 31, 2016 June 31, 2016 2016 Grants / Contracts 2 $1,175,486 $814,496 $210,000 Gifts $53,000 $3,250 $250 Cont. ED/ Outreach $0 $0 $0 Clinical Service $5,000 $0 $0 Other Contributions 3 $1,042,149 $1,042,149 $194,763 Knowledge Fund 4 $1,908,571 $1,525,667 $446,119 Interest earned $0 $0 $0 Total $4,184,206 $3,385,562 $851,132 Page 8

1estimates are for gross revenue. 2grants include only those awarded after that date. One grant during the current period grant is not included in the scorecard. 3Other contributions are from UNLV. 4Some of the knowledge fund income includes expenditures on faculty startup packages awarded prior to July 1, 2015. Page 9

Section IV: Weekly/Monthly Logs of NIPM Progress for Reporting Quarter All progress is related to the 15 milestones identified in Table 1. Monthly Report April 2016 Milestone 1. IRB approval NIPM worked with the IRB to revise our submitted protocol. Milestone 2. Implement a computer system We are still waiting for power to be brought to the new fat node at SWITCH. Milestone 3. Set up NGS pipeline We are still waiting for power to be brought to the new fat node at SWITCH. (After the fact, the power was not brought to the rack until the end of July We were wise to move it back to UNLV). Milestone 4. Set up personalized medicine database Our team is progressing in building this large database. We were having trouble uploading data into the commercial OrientDB database. Attempts are underway to identify the source of the problem Milestone 5. Conduct SOAPS trial NIPM has been meeting weekly with the PeopleSeq project consortium. NIPM cannot start this until milestone 1 is complete. Milestone 6. Establish Omics core Temporary space was requested from the UNLV administration. Milestone 7. Validate Omics core Milestone 8-10. Milestone 11. COBRE grant Still waiting to hear about score for submitted the COBRE grant. Milestone 12. Clinical Genetics services Purchase of an examination table and other needed equipment for clinical services were made. The decision is to go forward with the Center for Autism Spectrum Disorders as the initial location for clinical services. Milestone 13-15 Page 10

Monthly Report May 2016 Milestone 1. IRB approval We are waiting for the IRB to rule. Milestone 2. Implement a computer system SWITCH is taking too long to supply power. We moved the server back to UNLV and installed it. Milestone 3. Set up NGS pipeline We configured our new FAT node server. The necessary software is installed and running on the server. Milestone 4. Set up personalized medicine database The necessary tools for setting up an OrientDB database are available but there is a concern regarding the upload performance of the technology. We are researching alternative technologies and alternative configurations. Milestone 5. Conduct SOAPS trial NIPM has been meeting weekly with the PeopleSeq project consortium. NIPM cannot start this until milestone 1 is complete. Milestone 6. Establish Omics core The sequencing equipment arrived. Milestone 7. Validate Omics core Milestone 8-10 Not started yet Milestone 11. COBRE grant Still waiting to hear about score for submitted the COBRE grant. Milestone 12. Clinical Genetics services Efforts concerning arrangements for clinical services were established in regards to beginning seeing patients at the Center for Autism Spectrum Disorders. This included setting up clinic times, schedules, and deciding on initial intent of clinical services. Milestone 13-15 Page 11

Monthly Report June 2016 Milestone 1. IRB approval We provided more revisions to the protocol and are again awaiting approval. Milestone 2. Implement a computer system We now have one FAT node installed and in use. This combined with Cherry Creek is helping with our needs. NIPM has convened a working group of experts to define NIPM requirements, reduce these to computer hardware requirements, and design a system to meet our needs. Milestone 3. Setup NGS pipeline Additional testing and optimization of the software is in process. Milestone 4. Setup Personalized Medicine database Research on alternative technologies and alternative configurations continues. We have identified 5 other graph- document databases to test. Also is seems like memory is not the issue with orient db. Milestone 5. Conduct SOAPS Trial NIPM has been meeting weekly with the PeopleSeq project consortium. NIPM cannot start this until milestone 1 is complete. Milestone 6. Establish Omics core Illumina cam and installed the NextGen Sequencer and we performed our first test runs of the instrument. The quote came in for the permanent space and the UNLV administration decided it was too expensive to renovate the space and is now looking for other permanent space. NIPM also applied for a grant with the Lou Ruvo Center for Brain health to hire a staff member and purchase Genotyping equipment. Milestone 7. Validate Omics core Milestone 8-10 Milestone 11. COBRE grant Still waiting to hear about score for submitted the COBRE grant. Milestone 12. Clinical Genetics services Patient slots, and the initial contact of patients for appointments were made. Final inspection and approval of the Center for Autism Spectrum Disorders as a clinical site were made. Review of needs as per different clinicians involved at the site were reviewed. Page 12

Milestone 13-15 Section V: Appendix Appendix 1 Sales Pipeline Page 13

Appendix 2 Scorecard Supporting Documentation No documentation for this report. Page 14