Leaders in Pharmaceutical Business Intelligence (LPBI) Group

7:00-8:15         Coffee & Registration

8:30-9:30         Opening
                         Kevin Hrusovsky
                         PPH Summit Founder and Chair, CEO Quanterix    

LIVE @ Marriott, Cambridge Aviva Lev-Ari streaming live from Powering Precision Health Summit

Apple and Steve Jobs – Returned to Apple after Pixar – Jobs has teamed up with Microsoft.

Innovations @Apple: iPhone, iPad, iPod, TV Apple,

Innovations @High Tech Industry in the World: Uber, Facebook, Robots,

Science – leads the revolution and DISRUPTIVE innovations

Medicine – Cardiology, Neurology, Oncology: INFLAMMATION markers

• Speakers Affiliations
• Collaborations
• Leaders in the field
• 5% Patient Advocacy; 10% Investors, 20% Providers, SCIENTISTS

PRECISION HEALTH: DIGITAL REVOLUTION AND HEALTH

• lower costs on HC 40%, shift to prevention, 60% better access
• Sick care: Japan and France HC more productive – Life expectency is 8 yrs hight than the US
• Cancer, diabetes, In the US 31 out of 100,ooo reaches +100 yrs of age
• Cancer Women: BRCA
• Cancer Men: Prostate Cancer: PSA >10 – riskhigher
• Sugar consumption in the USA  – 216 Liters/person
• Obesity and Diabetes
• Food addiction: Salt, fat, sugar: 2/3 of the populations are obese
• Omega 6 overload – inflammation
• Neurological disease:

1. AD starts at 50 in some cases
2. Concussions in Sports 5-10% – leading to neurodegenerative diseases
3. Bicycle accidents at kids: no monitoring
4. Drug as environmental factor – TOXICITY: depression, Schisophrenia, cardiac Arythmia

• Digitizing biomarkers & Analytics: extreme specificity and sensitivity of Inflammation markers: Lowest DETECTION marker levels
• LIQUID BIOPSY – ACCURATE NON-INVASIVE – 20B THE MARKET FOR LIQUID BIOPSY
• Epigenetics: Twin Studies: Proteins – detections –

1. Suppression Inflammation Surveilence
2. Braf mutations – therapy
3. Cardiology: Mediteranean diet
4. Troponin-I: Can be seen before symptoms emerges
5. WEARABLE DEVICES: Detection >> Prevention >> Treatment Sick Care >>> HealthCare
6. unique opportunity to REVOLUTIONIZE MEDICINE – help patients sooner

Powering Precision Health with Science                          
Compelling technological and scientific advances are fueling a proposition that today’s healthcare can be radically improved and made more effective, accessible and economical by deploying disruptive technologies to carefully guide healthy living.  The potential for shifting our innovation focus from disease diagnostics and treatment (sick care) to early detection and disease prevention (precision healthcare) will be explored in oncology, neurology and cardiology as well as their underlying inflammation pathways.  Mobilizing this transformation requires the democratization of health assessments with digital technology, big data and wellness studies coupled with comprehensive policy and provider reconfiguration that incentivizes healthy living and “accountable” care.  Significant precision health advances are being realized in certain parts of the world and providing a credible blueprint for its potential.   Catalyzing our Precision Health initiative requires scientists, innovators, physicians, providers, regulators, investors and patient advocates to unite and build a collective vision for Precision Health.

Oncology                                         
9:30-10:45
9:30- 9:40       Introductions: Oncology Innovator Panel
                        Kevin Hrusovsky PPH Summit Founder and Chair, CEO Quanterix

 David Walt, PhD, Tufts University

Infectious disease 

1. Single molecule array (simoa) – digitization of signals beads in Alisas – beads loaded on disc array
2. Serum Cytokines – IL-10 and IL-8: at sub-femtomolar concentrations

Vaccination study: injection of these Cytokines: Human serum cytokine, baseline – COntrol Healthy Samples

Variation inter subjects in cytokine levels: Day One response evolution of th eImmune response

• day reported illness
• cytokine fluctuation
• cytokine expression levels
• IgG Simoa sensitivity (secondary infection); IgM (primary infection)

ONCOLOGY: Early Detection of Breast Cancer

Future technology:

• sensitive detection for BRCA
• 6-12% false positive in Mamography
• Breast cancer Biomarkers: Singleplex Simeo assays
• 8X-1000X improved sensitivity
• Assay tested in commercial kits
• SimOa for miRNA detection: 66 patients tested, prior to therapy: Marker 1,2,3

Individual protein assay were multiplexed

1. Three protein Signature: PLS-DA Classification: 84% precision Health vs BRCA Stage II
2. Sensitivity/specificity: on Biomarkers in BLOOD: 95.9% accuraccy Health vs. diagnosed BRCA

Protein Biomarkers in serum samples – cells secret, cells are invovled with mutations

• find binding agents

                                                   

Robert Weinberg, PhD,  MIT /Whitehead Institute

•  Early detection in colonoscopy is significant
• Breast CA – early detection  and effect on mortality: 705 OF WOMEN AT 85 have BRCA
• response to drugs in Cancer; diagnosis of relapse
• reduce Cancer Mortality ONLY by reduction of inscidence not early detection which – DX and TX does not change mortality – acquired somatic mutation
• Circulating tumor Cells & CIrculating DNA – Sequencing is very limited in its applicability for BRCA
• Genomics data integration iwth gene expression
• Reincentivise the young  – Pharma and Diagnostics — need to fund Postdocs in Academia

John Houston, PhD
                         Formerly SVP Bristol Myers Squibb   

• What is real and what is doable
• Advanced   Melanoma: markable accomplishments
• why some patients respond and why others do not – Biomarkers
• Combination drug  therapy in Oncology
• signature for response and non-response is critical
• Platform to capture data in retrospect

Phil Stephens, PhD
Foundation Medicine

1. 10,000 patients with cancer mutations
2. biomarkers for Target Therapy
3. combinations need be Target and immuno
4. Bladder Cancer is example were sequencing did help
5. RNA and DNA and beyond: making sequencing data on metastatic disease
6. diagnostic Industry needs regulation – Some Texts are not accurate and do not assists

Discussion Moderator: Kevin   – Biomarkers other Technologies mRNA, Liquid Biopsy                                      
                                                                                                                
9:40-10:00       Keynote Address Oncology:
                         David Walt, PhD
                         Tufts University

Beyond Genomics: Disruptive Approaches to Cancer and Infectious Disease Diagnostics
We have used the single molecule array  technology to screen dozens of potential biomarkers for their ability to diagnose various diseases and predict clinical outcomes.  The single molecule array technology has been used primarily for protein detection but is also applicable to the detection of nucleic acids, including DNA, mRNA, and microRNA, without any amplification.  Ultra-high sensitivity enables the detection of both protein and nucleic acid biomarkers at concentrations previously undetectable in blood. After measuring the candidate biomarkers, we employ classification algorithms to down-select the most informative biomarkers that correlate with the clinical information.  We have employed this approach to discover serum biomarkers for monitoring individuals over extended periods for infectious disease and for early detection of breast cancer.

10:00-10:45     Oncology Innovator Panel Discussion
Revolutionizing Oncology with Disruptive Technologies to Prevent, Detect, and Treat Cancer

10:45-11:15      Coffee break

Neurology                                       
11:15-12:30     Introductions: Neurology Innovator Panel
                      Kevin Hrusovsky
                      PPH Summit Founder and Chair, CEO Quanterix

Robert Stern, PhD
Boston University, School of Medicine, BU Alzheimer’s Disease and CTE Center
                                               

Doug Cole, MD – Neurologist and investor – Flagship Ventures
                                              

1. no powerful tools to understand AD 20 years ago,
2. Tools are now available – in 5-20 years tools will allow for Treatment development
3. Societal issue – leadership at University Presidents, Sports organization – grass root pressure like with No Smoking
4. commonality needs be explore across diseases to establish syndroms shared that will enable development of disease management and treatment

 

Jesse M. Cedarbaum, MD – Biogen 
                                                

1. Neurologist – worked with MS, Parkinson, AD – did not work with CTE
2. Soccer – Contact with the ball  – effect the structure of exon, synapsis, beta protein
3. TOOLS: Genetic risk allowing to play short or long durations
4. Football, soccer, baseball and tennis
5. WE NEED LARGE POOLS OF NEUROLOGICAL DISEASES IN PATIENTS – BECAUSE  there are common proteins involved and comorbidities vs present participation in clinical trials by diagnosis
6. all studies for Parkinson are not analysed in the context of AD
7. PCP needs tool to diagnose AD better than today the diagnosis is done
8. in Military training vibrations that causes CTE
                                                

Tim Fox
                                               Former NFL Safety, Sports Commentator                                                  
           Peter Cronin
                                               Former NFL Linebacker                                       

11:15-11:25     Tim Fox
                       Former NFL Safety, Sports Commentator  
                       Personal Perspective on The Impact of Repeated Concussions and CTE                 

11:25-11:45      Keynote Address Neurology:
                        Robert Stern, PhD
                        Boston University, School of Medicine, BU Alzheimer’s Disease and CTE Center

Diagnosing Chronic Traumatic Encephalopathy (CTE) During Life: Potential Fluid and Neuroimaging Biomarkers                           
Chronic Traumatic Encephalopathy (CTE) is a unique neurodegenerative disease associated with a history of repetitive head impacts, including concussive and sub-concussive trauma, such as that experienced by contact sport athletes (e.g., American football players, boxers). Currently CTE can only be diagnosed through postmortem neuropathological examination demonstrating the pathognomonic lesions of perivascular phosphorylated tau (p-tau) at the depths of the cortical sulci. The ability to diagnose CTE during life is critically important to understanding the epidemiology of the disease, as well as the examination of specific risk factors (e.g., head impact exposure, genetics) and the ability to conduct clinical trials for treatment and prevention. This talk will describe recent findings in the development of possible in vivo biomarkers for CTE, including Simoa plasma total tau, plasma exosomal tau, as well as tau PET imaging.

LIVE @PPHSUMMIT 

• $60Million NIH Grants
• Awareness, Prevention, Management
• Repetitive Head Impacts vs Concussions

1. effect on neuronal functioning
2. even one season causes cognitive, physiological changes in the brain
3. Boxing for long time
4. long time consecquences – Neuropathology
5. CTE – brain trauma, leads to progressive neuro-degeneration

• post consussion disease without symptoms of concussion
• like AD, microtubule-Associated Protein Tau – misfolded hyperphosphorilated form of tau (p-tau): Perivascular and Depth of Solci — >>>> Spread of areas with distruction
• Why it was not commonly observed ??
• CTE and Public Health: Contact Sports – REPETITIVE IMPACT
• Exposure: Severity and type of trauma
• rest between hits
• CTE vs PTSD, other injuries
• Diagnose during life: develop in vivo biomarkers
• How to create Biomarkers: DETECT Study: 100 NFL players vs Control – no sport involvement
• All imaging were not specific to Tau detection –
• Brain PET Tau Imaging developed: Invasive, expensive, we need a blood test
• Tau deposits
• Blood based Biomarkers for CTE – high sensitivity — FOllow up blood screening
• Plasma Exosomal Tau: Exosomes are cell-derived nanovescicles: Blood, saliva, urine
• generation of Neuronal Exosomes – extracellular space
• Exosomes isolation required – Measure Tau in Blood
• Quanterix_ Plasma total Tau – simoa HD-1
• Results: plasma T-Tau – difference NFL and control – NFL – Extreme T-Tau COncentration
• How to refine and validate Plasma T-Tau?
• relevance to AD – modify early predict sympthoms – Using DIgital Biomarkers
• Precision Health: Prevention and Tx of CTE:
• Concussions & subconclusive Hits >>> PreClinical, >>> Clinical CTE not dimented >> CTE Dementia= synaptic loss

11:45-11:55        Peter Cronin
Former NFL Linebacker
Personal Perspective on The Urgent Need For Detection and Treatment of CTE

• concussion with memory loss, mood changes,

11:55-12:30     Neurology Innovator Panel Discussion
Revolutionizing Neurology with Disruptive Technologies: Prevent, Detect and Treat
Concussions/CTE

12:30-1:15       Buffet style lunch

1:15-3:30         Scientific Tracks

Track 1 – Neurology – not attended
1:15-1:40         Jessica Gill, PhD, RN                 The Role of Proteomic Biomarkers of Brain Injuries
                         National Institute of Health
1:40-2:05         Danielle Graham, PhD               Accelerating exploratory fluid biomarker assay development in
Biogen                                       Neurodegenerative Disease
2:05-2:25         Alison Joyce, PhD                      Development of a Sensitive Homebrew Simoa Assay to Detect
Pfizer Inc                                    Leucine-Rich Repeat Kinase 2 (LRRK2)
2:25–3:00         Cheryl Wellington, PhD              Toward Precision Medicine in Canada: Two vignettes
                         University of British Columbia                   
3:00-3:25         Miriam Moscovitch-Lopatin       An Ultra-Sensitive Simoa Immunoassay for Quantifying BDNF
                          MGH                                          Levels in CSF in Early Huntington Disease: A Longitudinal PRE-
CELL Biomarker Study

Track 2 – Cardiology, Oncology, Inflammation, Infectious Disease

1:30-2:00         Ralph McDade, PhD      Ex-Luminex    Myriad RBM     

Triphase approach to biomarker pattern discovery for cancer immunotherapy and autoimmune disease

• Bi-Polar vs Depression – Diagnosis
• nostics for Depression Kit to determine which anti-depressant drug to prescribe
• xMAP Technology – immuno-assays
• 96 well plate
• robotic liquid handling – assay precision and reproducability
• proprietary matrix blockers
• Myriad Genetics is the Parent company
• Validation Parameters
• CLIA certified ELISA Amono assay
• Analyte: TNF-alpha, IFN-gamma (no marker in RA), IL-1 beta, IL-6, IL-17A
• DIsease state samples – RA – IL-1Betta
• Multiplexing
                                                           

2:00-2:30         John Yan                                     An Ultrasensitive Assay Format for Detecting PD/Biomarkers in
Takeda Pharmaceutical Co          Cell and Xenograft Tumor

• ULK1 important Autophage Initiating Kinase
• mTOR – -/+mTor treated with ULK1

                       
2:30-3:00         Rama Boyanapalli, PhD              The long and winding road to a highly sensitive RANKL Assay
                         Shire Company

• RANKL IS A PART OF THE NECROTIC FACTOR (TNF)
• PROTEIN BIOMARKER RANKL AND BONE STRENGTH (bone resorption) and bone formation – Vitamin D PGE@
• Commercial Kits available:Recombinant and Serum based
• IMOA technology ultrasensitive
• Antibody Selection: R&D System DUoSet human RANKL ELISA selection-

1. Capture Ab sonjugate to beads – MOUSE MONCLONAL
2. Detector Ab – GOAT POLYCLONAL
3. tested 12 commercially available Abs
4. Additional assay optimization
5. Criteria for QUALIFYING AN ASSAY:

• ASSAY SPECIFICITY
• MINIMUM REQUIRED DILUTION
• PRECISION
• Calibration curves with varying calibrator levels – for precision studies
• Comparing Simoa to ELISA Kit: RANKL concentration

 

3:00-3:30         Bonnie J. Howell, PhD                 Ultrasensitive Detection of Viral p24 Following Reactivation of
Merck                                          Latent HIV

• HIV Biology
• tratment
• reservoir detection
• HIV — affects t-Cells — AIDS
• life cycle of HIV-1
• Viral RNA, recapaged to virom and start another cycle of infection
• Treatment of ANtiviral therapies (ART)
• Persistent replication of the virus
• HIV Vure Means?
• Sterilization / eradicated of HIV free
• Remission/Functional
• get of ART for few years
• latent vells survuve deceased activation
• latent reservoir homeostatic proliferation
• latent cell reactivation
• reactivation
• Where do they hide?
• HIV – CNS, Gut, GI, GU, Bone marrow,
• Estimation 1 per million resting CD4 – Quantifying the HIV Rservoir

1. different PCR- and Culture based assays used to measure reservoir
2. poor correlation between assay
3. >95% provirus is defective – does not produce Vyron
4. Quanterix SImoa digital ELISA for ultrasensitive HIV p24 protein detection
5. serum convert stage – makes measurement of reservoir difficult
6. Merck optimized ultrasensitive p24 immunoasay
7. p24 detectd in gnotypically diverse HIV clinical isolates
8. HIV-1, CPZ, HIV-2, SIV-MM
9. Virus to kill strategy: IMMUNO-therapy – measuring protein so importent
10. Shock and kill

• Cells with latent HIV with
• cells with activated HIV
• Induction in ART-suppresant
• T-cell activation with stimulation Suppresant p24 Increases with reservoir size in most pt.
• PMA/Ionomycin, CD4+ T-cell Lysate as measured by TILDA
• HDACi induces p24 Expression in ART Suppressed HIV + Patients CD4+
• Latency-Reversing Agents
• Treatment with Multiple doses of Vorinostat
• Gag RNA – Assay: Baseline vs Post-VOR – HIV pt received 10 doses VOR administared in 72 hours
• Two doses of Vorinostat
• Dilution series

SUMMARY

p24 digital ELISA improves assay sensitivity and selectivity

p24 detected in genotypically diverse HIV clinical isolates
                         
3:30-4:00         Coffee Break

 

Cardiology and Inflammation

                                     
4:00-4:10         Introductions: Cardiology/Inflammation Panel
                         Kevin Hrusovsky
PPH Summit Founder and Chair

                                                  Dennis Ausiello, MD
                                                  Mass General HospitalEmeritus
                                                   Petr Jarolim, MD, PhD
 Brigham and Women’s Hospital, Dana Farber Cancer Institute 
Grace Colon, PhD
 InCarda Therapeutics, Inc. and ProterixBio, Inc.                                                            

4:10-4:30        Keynote Address Cardiology/Inflammation
                        Dennis Ausiello, MD
                        Mass General HospitalEmeritus

Mobilizing Precision Health is Within Reach
The data revolution, from genetic to digital, has provided a compelling need to assess wellness and its progression to disease. This is in direct contrast to the long standing approach in medicine of episodic and symptomatic measurement of disease and its progression to morbidity and mortality. Compelling data and science are fueling a proposition that today’s healthcare can be radically improved and made more effective, accessible and economical by deploying disruptive technologies to carefully monitor and guide healthy living.  We will explore the real potential of pre-symptomatic assessment of the human condition independent of time and place, with an improvement in disease prevention. Democratizing health assessments and monitoring with mobile devices, smart phones and community drug stores is an important opportunity for enabling early detection, preventative medicine and precision health.  Establishing disruptive detection technology and sampling strategies across multiple biomarker panels is key to enabling this vision.

4:30 -5:15        Cardiology and Inflammation Innovator Panel Discussion
Revolutionizing Cardiology with Disruptive Technologies: Prevent, Detect and Treat Cardiovascular
Disorders and Diabetes

5:15-5:30         Chair Summary and Summit Close

5:30-7:30         Cocktail Reception