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Archive for the ‘Personalized and Precision Medicine & Genomic Research’ Category


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Parkinson’s Disease (PD), characterized by both motor and non-motor system pathology, is a common neurodegenerative disorder affecting about 1% of the population over age 60. Its prevalence presents an increasing social burden as the population ages. Since its introduction in the 1960’s, dopamine (DA)-replacement therapy (e.g., L-DOPA) has remained the gold standard treatment. While improving PD patients’ quality of life, the effects of treatment fade with disease progression and prolonged usage of these medications often (>80%) results in side effects including dyskinesias and motor fluctuations. Since the selective degeneration of A9 mDA neurons (mDANs) in the substantia nigra (SN) is a key pathological feature of the disease and is directly associated with the cardinal motor symptoms, dopaminergic cell transplantation has been proposed as a therapeutic strategy.

 

Researchers showed that mammalian fibroblasts can be converted into embryonic stem cell (ESC)-like induced pluripotent stem cells (iPSCs) by introducing four transcription factors i.e., Oct4, Sox2, Klf4, and c-Myc. This was then accomplished with human somatic cells, reprogramming them into human iPSCs (hiPSCs), offering the possibility of generating patient-specific stem cells. There are several major barriers to implementation of hiPSC-based cell therapy for PD. First, probably due to the limited understanding of the reprogramming process, wide variability exists between the differentiation potential of individual hiPSC lines. Second, the safety of hiPSC-based cell therapy has yet to be fully established. In particular, since any hiPSCs that remain undifferentiated or bear sub-clonal tumorigenic mutations have neoplastic potential, it is critical to eliminate completely such cells from a therapeutic product.

 

In the present study the researchers established human induced pluripotent stem cell (hiPSC)-based autologous cell therapy. Researchers reported a platform of core techniques for the production of mDA progenitors as a safe and effective therapeutic product. First, by combining metabolism-regulating microRNAs with reprogramming factors, a method was developed to more efficiently generate clinical grade iPSCs, as evidenced by genomic integrity and unbiased pluripotent potential. Second, a “spotting”-based in vitro differentiation methodology was established to generate functional and healthy mDA cells in a scalable manner. Third, a chemical method was developed that safely eliminates undifferentiated cells from the final product. Dopaminergic cells thus produced can express high levels of characteristic mDA markers, produce and secrete dopamine, and exhibit electrophysiological features typical of mDA cells. Transplantation of these cells into rodent models of PD robustly restored motor dysfunction and reinnervated host brain, while showing no evidence of tumor formation or redistribution of the implanted cells.

 

Together these results supported the promise of these techniques to provide clinically applicable personalized autologous cell therapy for PD. It was recognized by researchers that this methodology is likely to be more costly in dollars and manpower than techniques using off-the-shelf methods and allogenic cell lines. Nevertheless, the cost for autologous cell therapy may be expected to decrease steadily with technological refinement and automation. Given the significant advantages inherent in a cell source free of ethical concerns and with the potential to obviate the need for immunosuppression, with its attendant costs and dangers, it was proposed that this platform is suitable for the successful implementation of human personalized autologous cell therapy for PD.

 

References:

 

https://www.jci.org/articles/view/130767/pdf?elqTrackId=2fd7d0edee744f9cb6d70a686d7b273b

 

https://www.ncbi.nlm.nih.gov/pubmed/31714896

 

https://www.ncbi.nlm.nih.gov/pubmed/23666606

 

https://www.ncbi.nlm.nih.gov/pubmed/27343168

 

https://www.ncbi.nlm.nih.gov/pubmed/21495962

 

https://www.ncbi.nlm.nih.gov/pubmed/28083784

 

https://www.ncbi.nlm.nih.gov/pubmed/20336395

 

https://www.ncbi.nlm.nih.gov/pubmed/28585381

 

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Tweets and Retweets by @AVIVA1950 and by @pharma_BI for 15th Annual Personalized Medicine Conference at Harvard Medical School – THE PARADIGM EVOLVES, November 13 – 14, 2019 • Harvard Medical School, Boston, MA

Real Time Press Coverage: Aviva Lev-Ari, PhD, RN

see also,

eProceedings 15th Annual Personalized Medicine Conference at Harvard Medical School – THE PARADIGM EVOLVES, November 13 – 14, 2019 • Harvard Medical School, Boston, MA

https://pharmaceuticalintelligence.com/2019/07/19/15th-annual-personalized-medicine-conference-at-harvard-medical-school-the-paradigm-evolves-november-13-14-2019-%e2%80%a2-harvard-medical-school-boston-ma/

 

 

Tweets by @AVIVA1950 and by @pharma_BI

Aviva Lev-Ari
@AVIVA1950

#PMConf

Donald L. Siegel, Ph.D., M.D., Director, Division of Transfusion Medicine & Therapeutic Biology, Director, Clinical Cell and Vaccine Production Facility, UPenn’s Perelman School of Medicine no relations explored between Immune T cells and microbiome

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Aviva Lev-Ari
@AVIVA1950

#PMConf

Paul Stoffels, M.D., Vice Chairman, Executive Committee, Chief Scientific Officer, Johnson & Johnson Impact of Mirobiome it plays a key role in many diseases difficult to develop therapeutics derived from microbiome data

1
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Aviva Lev-Ari
@AVIVA1950

#PMConf

Harpreet Singh, Ph.D., CEO, Immatics T Cell peptide started 15 years ago Peptonomics,  tumors of solid cancer – cell therapies selected from libraries  off the shelf cells from health donors Biologics bridges tumor cells and solid cells

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Aviva Lev-Ari
@AVIVA1950

#PMConf

Donald L. Siegel, Ph.D., M.D., Director, Division of Transfusion Medicine & Therapeutic Biology, Director, Clinical Cell and Vaccine Production Facility, UPenn’s Medicine CAR-T therapy started the Transfusion Medicine & Therapeutic Biology industry

Aviva Lev-Ari
@AVIVA1950

#PMConf

Paul Stoffels, M.D., Vice Chairman, Executive Committee, Chief Scientific Officer, Johnson & Johnson Combination therapy emerges, MOA partnerships: cell therapy can transform cancer treatment INFECTIOUS disease had Global impact need stop the virus

Aviva Lev-Ari
@AVIVA1950

#PMConf

Paul Stoffels, M.D., #CSO

Platforms are established, every 20-30 another one emergences access to data – critical platform AI for diagnostics and decision making biomarkers J&J try to learn on every disease: Lungs and GI Diagnosis HIV Vaccine

Aviva Lev-Ari
@AVIVA1950

#PMConf

Paul Stoffels, M.D., Vice Chairman, Executive Committee, Chief Scientific Officer, Johnson & Johnson Goals of medicine in 2019 early detection Vaccines in disease prevention Longevity

Aviva Lev-Ari
@AVIVA1950

#PMConf

Joseph B. Martin, M.D., Ph.D., Dean Emeritus

fascinating personal history story on development of interest in genetic analysis

Aviva Lev-Ari
@AVIVA1950

#PMConf

Michael J. Pellini, MD Diagnostics Pain management  Patients can fight more broadly F for sharing data and data exchange 80% patients do not access Academic Centers for treatment

Aviva Lev-Ari
@AVIVA1950

#PMConf

Michael J. Pellini, MD surgery, chemo, radiation – cost, harmful, INEFFECTIVE, Dr. Reza Columbia Medical School Oncologist 35 years How are we doing with technology? Very remarkable Clinical Utility to the Payer Regulatory – a super star in ten years

Aviva Lev-Ari
@AVIVA1950

#PMConf

Stephen L. Eck, Carl June, UPenn Beyond Cancer: Chronic diseases have systemic of specific immune or autoimmune components: CNS, neurodegenerative and Diabetes, Sickle cell anemia – treatment by cell therapy microphages

Aviva Lev-Ari
@AVIVA1950

#PMConf

Stephen L. Eck, Carl June, UPenn Cost of cell transfection therapy: Cost of Goods, Cost of Labor – pay for performance,  Manufacture in NJ shipped to Europe – not effective

Aviva Lev-Ari
@AVIVA1950

#PMConf

Stephen L. Eck, Carl June, UPenn Similarity between Transfusion Medicine industry and Cell therapy – Transfection of cells therapy  Manufacturing of Cells for transfection: Over regulation like in small molecules vs too little regulation

Aviva Lev-Ari
@AVIVA1950

#PMConf

Stephen L. Eck, Carl June, UPenn engineering T cells life farming – innovation is the driver, FDA is evolving in handling patents involved in Cell engineering Regulatory science needs to evolve in light of gene therapy in Human cell line in China

Aviva Lev-Ari
@AVIVA1950

#PMConf

Stephen L. Eck, Carl June, UPenn Children vs Adults 2011 reported better results in Adults, children’s immune system is evolving  In 2019 – 13 biotech companies in CAR-T cell therapies, Gene therapy is growing FDA, drug cycle T cells vs stem cells

Aviva Lev-Ari
@AVIVA1950

#PMConf

15th Annual meeting is at a historic moment in Boston where Prof. Church launched the Human Genome Project and Eric Launder at MIT and the Cancer Genome Project. Genzyme conceived gene therapy sold to Sanofi for $ Billion  Foundation Medicine

1

Aviva Lev-Ari
@AVIVA1950

#PMConf

Edward Abrahams, Ph.D., President, PMC 170 drugs with biomarkers, up 15% from 2000 in Biomarker strategy Gene therapy started in 2005, today personalized medicine is becoming standard of care. Science & Technology need additional friendly environment

1

Aviva Lev-Ari
@AVIVA1950

#PMConf

Kenna R. Mills Shaw, Ph.D., MD Anderson Institute does not sequence genome of each patient unlike Dana Farber clinicians need to access information for decision making when disease progresses – what new test to order data sharing inside the institute

Aviva Lev-Ari
@AVIVA1950

#PMConf

Daryl Pritchard, Ph.D., Senior Vice President, Science Policy, PMC Genomic sequencing for a single test that covers many biomarkers Improve treatment efficiency Growing recognition of the need to demonstrate value, evidence for Payers to pay

1

Aviva Lev-Ari
@AVIVA1950

#PMConf

Ammar Qadan, Vice President, Global Head of Market Access, Illumina Illumina is building evidence for Harvard Pilgrim on theirs patient data on risk pregnancies Illumina is expanding  building evidence for ALL rare diseases for all Test diagnostics

Aviva Lev-Ari
@AVIVA1950

#PMConf

Roy J. Gandolfi, M.D., Medical Director, SelectHealth, UT is the Payer of Intermountain Healthcare, UT Regional approach vs National perspective medical policies requires experts for Payer to approve a treatment Consumer in the health plan

Aviva Lev-Ari
@AVIVA1950

#PMConf

Lincoln Nadauld, M.D., Ph.D., Chief, Precision Health, Intermountain Healthcare, UT Precision Oncology Program: Need, study, analysis outcome, publish dataPharmacogenetics testing will be covered for all employees & Neonatal

Aviva Lev-Ari
@AVIVA1950

#PMConf

Peter J. Neumann, Sc.D., Tufts Medical Center clinical utility evidence of value: saving by diagnostics cost for quality cost of diagnostics cost effectiveness – characterize utility cost effectiveness – study Value to families value of knowledge

Aviva Lev-Ari
@AVIVA1950

#PMConf

Ammar Qadan, Vice President, Global Head of Market Access, Illumina Illumina is partnering with providers and Payer Illumina & Blue Cross Blue Shield 150 Million are covered for genomics 2500 genomics test done Under utilization educate physician

Aviva Lev-Ari
@AVIVA1950

#PMConf

Mark P. Stevenson, COO Thermo Fisher Scientific Context: Therapy selection in personalized medicine navigate diagnostics in use and policies when implementations is considered Physicians need precise testing now Payers evidence of utility is needed

1

Aviva Lev-Ari
@AVIVA1950

#PMConf

Mark P. Stevenson, Executive Vice President, Chief Operating Officer, Thermo Fisher Scientific Patient Outcome – Data analytics, ML, AI for genomics, proteomics, metabolomics, Tests must be precise and inform the diagnosis by diagnostics Solutions

Aviva Lev-Ari
@AVIVA1950

#PMConf

Paul Stoffels, M.D., Vice Chairman, Executive Committee, Chief Scientific Officer, Johnson & Johnson Passion of Scientists pharmaceutics development is based on insights looking into the future – important goal to solve

Aviva Lev-Ari
@AVIVA1950

#PMConf

best conference on Personalized Medicine in 15 years eProceedings 15th Annual Personalized Medicine Conference at Harvard Medical School – THE PARADIGM EVOLVES, November 13 – 14, 2019 • Harvard Medical School, Boston, MA

eProceedings 15th Annual Personalized Medicine Conference at Harvard Medical School – THE PARADIGM…
eProceedings 15th Annual Personalized Medicine Conference at Harvard Medical School – THE PARADIGM EVOLVES, November 13 – 14, 2019 • Harvard Medical School, Boston, MA   The 15th Annual …
pharmaceuticalintelligence.com

Aviva Lev-Ari
@AVIVA1950

Your synopsis of the best Personalized Medicine Conference organized to date #PMConf

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Aviva Lev-Ari
@AVIVA1950
·
#PMConf @pharma_BI @AVIVA1950 best conference on Personalized Medicine in 15 years eProceedings 15th Annual Personalized Medicine Conference at Harvard Medical School – THE PARADIGM EVOLVES, November 13 – 14, 2019 • Harvard Medical School, Boston, MA pharmaceuticalintelligence.com/2019/07/19/15t

 Retweet by @AVIVA1950

Aviva Lev-Ari
@AVIVA1950

A true leader in Pharmaceutical domain, also Member of the National Academy of Art and Sciences #PMConf

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Cynthia Bens
@bens_cynthia
·
Introducing the amazing @ScottGottliebMD was a highlight of #pmconf. His vision for balanced regulatory and coverage policies is desperately needed now to support the future of #personalizedmedicine @permedcoalition

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Aviva Lev-Ari
@AVIVA1950

#PMConf

Best Case study

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PMC
@permedcoalition
·
This year’s #PMConf case study on the @TheDDFund puts a spotlight on what one can do to combine modern entrepreneurial finance approaches to tackle a very complex problem such as Alzheimer’s Disease. @RHamermesh @HarvardHBS #PMConf

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Aviva Lev-Ari
@AVIVA1950

#PMConf

Edward Abrahams, Ph.D., President, PMC 170 drugs with biomarkers, up 15% from 2000 in Biomarker strategy Gene therapy started in 2005, today personalized medicine is becoming standard of care. Science & Technology need additional friendly environment

1

Genomic Health®
@GenomicHealth

We’re proud to announce Steve Shak is the recipient of the Leadership in Personalized Medicine Award at the 15th Annual Personalized Medicine Conference: The Paradigm Evolves. Please come and see him speak at the conference. bit.ly/2lMAteZ #PMConf

Image

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An Intelligent DNA Nanorobot to Fight Cancer by Targeting HER2 Expression

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

HER2 is an important prognostic biomarker for 20–30% of breast cancers, which is the most common cancer in women. Overexpression of the HER2 receptor stimulates breast cells to proliferate and differentiate uncontrollably, thereby enhancing the malignancy of breast cancer and resulting in a poor prognosis for affected individuals. Current therapies to suppress the overexpression of HER2 in breast cancer mainly involve treatment with HER2-specific monoclonal antibodies. However, these monoclonal anti-HER2 antibodies have severe side effects in clinical trials, such as diarrhea, abnormal liver function, and drug resistance. Removing HER2 from the plasma membrane or inhibiting the gene expression of HER2 is a promising alternative that could limit the malignancy of HER2-positive cancer cells.

 

DNA origami is an emerging field of DNA-based nanotechnology and intelligent DNA nanorobots show great promise in working as a drug delivery system in healthcare. Different DNA-based nanorobots have been developed as affordable and facile therapeutic drugs. In particular, many studies reported that a tetrahedral framework nucleic acid (tFNA) could serve as a promising DNA nanocarrier for many antitumor drugs, owing to its high biocompatibility and biosecurity. For example, tFNA was reported to effectively deliver paclitaxel or doxorubicin to cancer cells for reversing drug resistance, small interfering RNAs (siRNAs) have been modified into tFNA for targeted drug delivery. Moreover, the production and storage of tFNA are not complicated, and they can be quickly degraded in lysosomes by cells. Since both free HApt and tFNA can be diverted into lysosomes, so,  combining the HApt and tFNA as a novel DNA nanorobot (namely, HApt-tFNA) can be an effective strategy to improve its delivery and therapeutic efficacy in treating HER2-positive breast cancer.

 

Researchers reported that a DNA framework-based intelligent DNA nanorobot for selective lysosomal degradation of tumor-specific proteins on cancer cells. An anti-HER2 aptamer (HApt) was site-specifically anchored on a tetrahedral framework nucleic acid (tFNA). This DNA nanorobot (HApt-tFNA) could target HER2-positive breast cancer cells and specifically induce the lysosomal degradation of the membrane protein HER2. An injection of the DNA nanorobot into a mouse model revealed that the presence of tFNA enhanced the stability and prolonged the blood circulation time of HApt, and HApt-tFNA could therefore drive HER2 into lysosomal degradation with a higher efficiency. The formation of the HER2-HApt-tFNA complexes resulted in the HER2-mediated endocytosis and digestion in lysosomes, which effectively reduced the amount of HER2 on the cell surfaces. An increased HER2 digestion through HApt-tFNA further induced cell apoptosis and arrested cell growth. Hence, this novel DNA nanorobot sheds new light on targeted protein degradation for precision breast cancer therapy.

 

It was previously reported that tFNA was degraded by lysosomes and could enhance cell autophagy. Results indicated that free Cy5-HApt and Cy5-HApt-tFNA could enter the lysosomes; thus, tFNA can be regarded as an efficient nanocarrier to transmit HApt into the target organelle. The DNA nanorobot composed of HApt and tFNA showed a higher stability and a more effective performance than free HApt against HER2-positive breast cancer cells. The PI3K/AKT pathway was inhibited when membrane-bound HER2 decreased in SK-BR-3 cells under the action of HApt-tFNA. The research findings suggest that tFNA can enhance the anticancer effects of HApt on SK-BR-3 cells; while HApt-tFNA can bind to HER2 specifically, the compounded HER2-HApt-tFNA complexes can then be transferred and degraded in lysosomes. After these processes, the accumulation of HER2 in the plasma membrane would decrease, which could also influence the downstream PI3K/AKT signaling pathway that is associated with cell growth and death.

 

However, some limitations need to be noted when interpreting the findings: (i) the cytotoxicity of the nanorobot on HER2-positive cancer cells was weak, and the anticancer effects between conventional monoclonal antibodies and HApt-tFNA was not compared; (ii) the differences in delivery efficiency between tFNA and other nanocarriers need to be confirmed; and (iii) the confirmation of anticancer effects of HApt-tFNA on tumors within animals remains challenging. Despite these limitations, the present study provided novel evidence of the biological effects of tFNA when combined with HApt. Although the stability and the anticancer effects of HApt-tFNA may require further improvement before clinical application, this study initiates a promising step toward the development of nanomedicines with novel and intelligent DNA nanorobots for tumor treatment.

 

References:

 

https://pubs.acs.org/doi/10.1021/acs.nanolett.9b01320

 

https://www.ncbi.nlm.nih.gov/pubmed/27939064

 

https://www.ncbi.nlm.nih.gov/pubmed/11694782

 

https://www.ncbi.nlm.nih.gov/pubmed/27082923

 

https://www.ncbi.nlm.nih.gov/pubmed/25365825

 

https://www.ncbi.nlm.nih.gov/pubmed/26840503

 

https://www.ncbi.nlm.nih.gov/pubmed/29802035

 

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Single-cell RNA-seq helps in finding intra-tumoral heterogeneity in pancreatic cancer

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Pancreatic cancer is a significant cause of cancer mortality; therefore, the development of early diagnostic strategies and effective treatment is essential. Improvements in imaging technology, as well as use of biomarkers are changing the way that pancreas cancer is diagnosed and staged. Although progress in treatment for pancreas cancer has been incremental, development of combination therapies involving both chemotherapeutic and biologic agents is ongoing.

 

Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (PDAC) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease.

 

The immune system varies in cell types, states, and locations. The complex networks, interactions, and responses of immune cells produce diverse cellular ecosystems composed of multiple cell types, accompanied by genetic diversity in antigen receptors. Within this ecosystem, innate and adaptive immune cells maintain and protect tissue function, integrity, and homeostasis upon changes in functional demands and diverse insults. Characterizing this inherent complexity requires studies at single-cell resolution. Recent advances such as massively parallel single-cell RNA sequencing and sophisticated computational methods are catalyzing a revolution in our understanding of immunology.

 

PDAC is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. In the present study to comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, single-cell RNA-seq (scRNA-seq) was employed to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases. The diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, were identified in PDAC.

 

The researchers found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, it was found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, the findings provided a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/31273297

 

https://www.ncbi.nlm.nih.gov/pubmed/21491194

 

https://www.ncbi.nlm.nih.gov/pubmed/27444064

 

https://www.ncbi.nlm.nih.gov/pubmed/28983043

 

https://www.ncbi.nlm.nih.gov/pubmed/24976721

 

https://www.ncbi.nlm.nih.gov/pubmed/27693023

 

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eProceedings 15th Annual Personalized Medicine Conference at Harvard Medical School – THE PARADIGM EVOLVES, November 13 – 14, 2019 • Harvard Medical School, Boston, MA

 

The 15th Annual Personalized Medicine Conference at Harvard Medical School will explore the science, business, and policy issues facing personalized medicine as scientists refine their understanding of how groundbreaking molecular diagnostics augmented by artificial intelligence, advanced data analytics, and digital health applications can empower both physicians and patients with information about how an expanded set of biological characteristics — including those found in the proteome and microbiome — may influence their health and their responses to increasingly impactful therapies.

 

WELCOME RECEPTION – NOVEMBER 13, 2019 – 6:15 P.M.

at the Isabella Stewart Gardner Museum, 25 Evans Way, Boston, MA 02115

http://www.personalizedmedicineconference.org/schedule/

 

Dear Colleague:

Use the link to access videos of the keynote sessions

featuring Scott Gottlieb, M.D., of the American Enterprise

Institute; Carl June, M.D., of the University of Pennsylvania;

Steven Shak, M.D., of Genomic Health; and Paul Stoffels,

M.D., of Johnson & Johnson.

As senior leaders from the GO2 Foundation for Lung Cancer, Harvard Pilgrim Health Care, the Institute for Clinical and Economic Review, M2Gen, and Novartis walked off the stage after the 15th Annual Personalized Medicine Conference at Harvard Medical School‘s final session, which was titled “Toward a Shared Value Proposition in Health Care,” Natasha Loder, Health Policy Editor, The Economist, told me it was “remarkable” to “see all of these people discuss the issues together” as she prepares to write a feature story on personalized medicine.

Her comments capture the spirit of this year’s conference and speak to PMC’s approach to advancing personalized medicine.

From: “Christopher Wells (PMC)” <cwells@personalizedmedicinecoalition.org>

Reply-To: “Christopher Wells (PMC)” <cwells@personalizedmedicinecoalition.org>

Date: Thursday, November 21, 2019 at 2:05 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Thank You for Joining Us

ANNOUNCEMENT

 

Leaders in Pharmaceutical Business Intelligence (LPBI) Group will cover this event in Real Time for pharmaceuticalintelligence.com 

In attendance generating in realtime event’s eProceeding and social media coverage by

 

Aviva Lev-Ari, PhD, RN

Director & Founder

Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

Editor-in-Chief

http://pharmaceuticalintelligence.com 

e-Mail: avivalev-ari@alum.berkeley.edu

(M) 617-775-0451

https://cal.berkeley.edu/AvivaLev-Ari,PhD,RN

SkypeID: HarpPlayer83          LinkedIn Profile        Twitter Profile

#PMConf

@pharma_BI

@AVIVA1950

AGENDA

Schedule

PART I

Diagnosing, Different

8:00 a.m.
Registration and Breakfast

Joseph B. Martin Conference Center at Harvard Medical School
77 Avenue Louis Pasteur, Boston, MA 02115

8:50 a.m.
Opening Remarks

SPEAKER | Edward Abrahams, Ph.D., President, Personalized Medicine Coalition

  • 170 drugs with biomarkers, up 15% from 2000 in Biomarker strategy
  • Gene therapy started in 2005, today personalized medicine is becoming standard of care.
  • Science & Technology need additional friendly environment for market penetration into care delivery
8:55 a.m.
Welcoming Remarks

SPEAKER | Raju Kucherlapati, Ph.D., Paul C. Cabot Professor of Genetics, Harvard Medical School

  • 15th Annual meeting is at a historic moment in Boston where Prof. Church launched the Human Genome Project and Eric Launder at MIT and the Cancer Genome Project.
  • Genzyme conceived gene therapy sold to Sanofi for $ Billion
  • Foundation Medicine acquired by Roche for $ Billion
  • Cystic Fibrosis – therapy discovery in Boston
  • MGH, Dana Farber, Lung Cancer discovery in 2004 theraphy PD-1
  • BWH, Dana Farber, sequence every patient at DF and treatment is guided by the genomic profile
  • 1993 was Millianum start, today Takeda – genetics in disease, initiated PMC
  • Promote Personalized Medicine by the Annual conference, now 15th in a row – promotion of PM is continuing in MA and beyond
  • Case studies at HBS – Kraft Center for Personalized Medicine
9:00 a.m.
The Era of the ‘Living Drug:’ A Keynote Conversation With Dr. Carl June, Pioneer of CAR T-cell Therapy

During this opening keynote session, the University of Pennsylvania’s Dr. Carl June, the discoverer of the chimeric antigen receptor (CAR) T-cell therapies that are unlocking a new era of personalized cancer care, will join Immatics US Chief Medical Officer Dr. Stephen L. Eck for a wide-ranging conversation about the future of personalized medicine, touching on issues including but not limited to access and affordability, regulation and manufacturing, and T-cell therapies beyond cancer.
» Read More

MODERATOR | Stephen L. Eck, M.D., Ph.D., Chief Medical Officer, Immatics US

Carl June, M.D., Richard W. Vague Professor in Immunotherapy, University of Pennsylvania

  • 1997 first patient treated – 15 years follow up CAR-T cells survived, 3 patient were infused, 2 out of 3 leukemia cell free.
  • Children vs Adults 2011 reported better results in Adults, children’s immune system is evolving
  • In 2019 – 13 biotech companies in CAR-T cell therapies, Gene therapy is growing
  • FDA, drug cycle T cells vs stem cells: engineering T cells life farming – innovation is the driver, FDA is evolving in handling patents involved in Cell engineering
  • Regulatory science needs to evolve in light of gene therapy in Human cell line in China has investments government and VC backed,
  • Similarity between Transfusion Medicine industry and Cell therapy – Transfection of cells therapy
  • Manufacturing of Cells for transfection: Over regulation like in small molecules vs too little regulation
  • Cost of cell transfection therapy: Cost of Goods, Cost of Labor – pay for performance,
  • Manufacture in NJ shipped to Europe – not effective
  • Beyond Cancer: Chronic diseases have systemic of specific immune or autoimmune components: CNS, neurodegenerative and Diabetes, Sickle cell anemia – treatment by cell therapy microphages
  • Diagnostics innovations: Epigenetics, cell sequencing,
  • Liability of a product that everyone wants: Class action law suit,
  • N of 1,
  • China ahead of US, Europe is behind US
  • How to fund and how to transfer from University Hospitals to community Hospital.
9:45 a.m.
Transformative Technologies: Previewing the Value Proposition and Outlook for Disruptive Tools Designed to Enable Personalized Medicine

Emerging personalized medicine technologies may help facilitate earlier interventions that eliminate the need for expensive treatment of advanced diseases that have devastating consequences for patients. They can also help target treatments to only those patients who will benefit. But the success of these technologies depends on whether they can be integrated into a health system that has historically focused on treating diseases after symptoms have intensified, usually based on the assumption that every patient taking a given medication will respond to the treatment in a similar way.

During this session, Section 32 Managing Partner Dr. Michael J. Pellini will moderate a discussion between industry representatives and a payer about the value proposition and outlook for disruptive technologies that are designed to support more informed disease prevention and treatment plans. The conversation will focus on how developments in areas including but not limited to artificial intelligence, data analytics, genomic sequencing, liquid biopsies, and proteomics may impact the prevention, diagnosis, and treatment of diseases including cancer, cardiovascular diseases, and diabetes.
» Read More

MODERATOR | Michael J. Pellini, M.D., Managing Partner, Section 32

  • surgery, chemo, radiation – cost, harmful, INEFFECTIVE, Dr. Reza Columbia Medical School Oncologist 35 years
  • How are we doing with technology? Very remarkable
  • Clinical Utility to the Payer
  • Regulatory – a super star in ten years, Dr. Gottlieb
  • Diagnostics
  • Pain  management
  • Patients can fight more broadly
  • F for sharing data and data exchange
  • 80% patients do not access Academic Centers for treatment
  • Challenge: Not each Payer needs to partner – need for a “coalition” of Payers
  • Standards: Will Payers welcome Government to provide guides – SHARING DATA is a guideline from the Government, i.e., Cystic Fibrosis where data was shared the most – success achieved faster

 

Steven J. Kafka, Ph.D., Partner, Third Rock Ventures; Executive Chairman, Thrive Earlier Detection

  • ex-Millenium, ex-Foundations,
  • Earlier detection of multiple cancers in Healthy individuals, Blood test – developed at John Hopkins, negative vs positive survival curve, early vs late stage
  • genetic profiling genotype used with the Blood test

Nancy Mendelsohn, M.D., Chief Medical Officer, Special Needs Initiative, UnitedHealth Group

  • Pediatrician
  • 2years with UniterHealthCare
  • Better outcome from more expensive treatment is justified
  • How to make effective treatment to rural areas, populations without access

Eric Schadt, Ph.D., CEO, Sema4

  • Spun off Mount Sinai 2 years ago, transfer of innovations to patients is slow, deriving insight is not easy
  • COmplications of pregnancy

Roy Smythe, M.D., CEO, SomaLogic

  • Access to technology and equity is an issue, delivery of care was pure,
  • SomaLogic, measurement of protein expression, applied to predict risk for future disease
  • Many Omics companies, Payers will bet on whom?
  • Standards
10:45 a.m.
Networking Break
11:15 a.m.
Developing Diagnostics — Opportunities and Challenges in Personalized Medicine: A Two-Part Discussion

Diagnostic test developers are working to make personalized medicine possible by giving physicians tools that help them select the optimal treatment for every patient. Doing so requires that they navigate a complex business and policy landscape while being mindful of the day-to-day needs of payers and health care providers.

In this context, Mr. Mark P. Stevenson, Executive Vice President, Chief Operating Officer, Thermo Fisher Scientific, will take 10 minutes to introduce this two-part discussion titled “Developing Diagnostics — Opportunities and Challenges in Personalized Medicine.”

INTRODUCTION | Mark P. Stevenson, Executive Vice President, Chief Operating Officer, Thermo Fisher Scientific

  • Context: Therapy selection in personalized medicine navigate diagnostics in use and policies when implementations is considered
  • Physicians need precise testing now
  • Payers – evidence of utility is needed
  • Patient Outcome – Data analytics, ML, AI for genomics, proteomics, metabolomics,
  • Tests must be precise and inform the diagnosis by diagnostics
  • Solutions are
  1. Chemical testing
  2. Immune therapy testing
  3. test utilization
  4. test coverage
  5. scaling
  6. Standardization of care in each Hospital, medical education
  7. Diagnostics & Pharma

 

Discussion Part 1
Developing Diagnostics — From Concept to the Clinic: Perspectives on the Landscape for Developing and Integrating Personalized Medicine Diagnostics into Health Systems

To kick off the “Developing Diagnostics” discussion, Moffitt Cancer Center’s DeBartolo Family Personalized Medicine Institute Medical Director Dr. Howard McLeod will moderate a conversation among leaders from the clinical, diagnostics, IT, and pharmaceutical communities about the landscape for developing and integrating personalized medicine diagnostics into health systems.
» Read More

MODERATOR | Howard McLeod, Pharm.D., Medical Director, DeBartolo Family Personalized Medicine Institute at Moffitt Cancer Center

Assaf Halevy, Founder, CEO, 2bPrecise

  • challenge – which genetic test id relevant for which patient
  • genomic signature available to match
  • close the loop with the physician from testing, research to therapy
  • Bridge needed to assist physicians to select medications within a class: SSRI based on genomics profile

Kris Joshi, Ph.D., Executive Vice President, President, Network Solutions, Change Healthcare is the Largest IT Healthcare in the US

  • Use of Data
  • Personalized Diagnostics: Education of patients and patient taking charge because OUT OF POCKET cost till deductible is reached is very high $800 for cancer diagnostics before diagnosis is been established
  • Patients access of own medical records by 2 million patients in the US
  • Molecular diagnostics
  • Genomics data management

Peter Maag, Ph.D., CEO, CareDx

  • Transplantation patients – prolong survival of populations using markers vs negative longevity of one patient
  • Diagnostics tied to registry to demonstrate efficacy of treatment
  • 94% survival after 1 year — no one survive 5 years
  • Data sharing is long term view
  • Consortium of 27 competing organization sharing data

Hakan Sakul, Ph.D., Vice President, Head of Diagnostics, Worldwide R & D and Medical, Pfizer

  • Responsive to drug and drug efficacy is determined by diagnostics test
  • Regulatory oversight
  • consistency across countries using same drugs and same diagnostics

Kenna R. Mills Shaw, Ph.D., Executive Director, MD Anderson Institute for Personalized Cancer Therapy

  • MD Anderson Institute does not sequence genome of each patient unlike Dana Farber
  • clinicians need to access information for decision making when disease progresses – what new test to order
  • data sharing inside the institution is not complete HOW data can be shared across institution

Discussion Part 2
Developing Diagnostics — The Role of Research: A Closer Look at Efforts to Encourage the Clinical Adoption of Personalized Medicine Diagnostics by Studying the Clinical and Economic Utility of Genomic Sequencing

During the second portion of the “Developing Diagnostics” session, a health care provider, a health economist, an industry leader, and a payer representative will join moderator and Personalized Medicine Coalition Senior Vice President for Science Policy Dr. Daryl Pritchard to examine the impact of emerging research on the clinical and economic utility of genomic sequencing for patients with diseases including but not limited to cancer and suspected rare diseases.
» Read More

MODERATOR | Daryl Pritchard, Ph.D., Senior Vice President, Science Policy, Personalized Medicine Coalition

  • Genomic sequencing for a single test that covers many biomarkers
  • Improve treatment efficiency
  • Growing recognizion of the need to demonstrate value, evidence for Payers to pay
  • barriers for adoption of genomic sequencing

Roy J. Gandolfi, M.D., Medical Director, SelectHealth, UT is the Payer of Intermountain Healthcare, UT

  • Regional approach vs National perspective
  • medical policies requires experts for Payer to approve a treatment
  • Consumer in the health plan – they buy insurance, self insure, safety, quality care, keep premium to affort care insurance

Lincoln Nadauld, M.D., Ph.D., Chief, Precision Health, Intermountain Healthcare, UT

  • Precision Oncology Program: Need, study, analysis outcome, publish data
  • Pharmacogenetics testing will be covered for all employees
  • Neonatal, genomic sequence of all neonatal patients
  • 500,000 people to be sequenced: Genomic information of every medical chart and measure clinical and economic outcomes

Peter J. Neumann, Sc.D., Director, Center for the Evaluation of Value and Risk in Health at the Institute for Clinical Research and Health Policy Studies, Tufts Medical Center

  • clinical utility
  • evidence of value: saving by diagnostics
  • cost for quality
  • cost of diagnostics
  • cost effectiveness – characterize utility
  • cost effectiveness – study
  • Value to families
  •  value of knowledge
  • externalities

Ammar Qadan, Vice President, Global Head of Market Access, Illumina

  • Illumina is partnering with providers and Payer
  • Illumina & Blue Cross Blue Shield – 150 Million are covered for genomics 2500 genomics test done
  • Under utilization – education of physician needed
  • Illumina is building evidence for Harvard Pilgrim on theirs patient data on risk pregnancies
  • Illimina is expanding  building evidence for ALL rare diseases for all Test diagnostics developers
12:55 p.m.
Seated Luncheon
2:10 p.m.
Overcoming Opioids: Considering the Potential of Personalized Medicine to Address the Opioid Crisis in the US

Emerging technologies present new opportunities to study the genetic, biological, and environmental factors that drive public health crises, with an eye toward developing personalized medicine health care strategies that can mitigate their devastating consequences.

During this session, Dr. Alissa M. Resch, Chief Scientific Officer, Coriell Institute for Medical Research, will explore the significance of Coriell’s ongoing effort to inform interventions that may help prevent opioid addiction by identifying with more precision which patients are most likely to develop dependency on this class of drugs.
» Read More

SPEAKER | Alissa M. Resch, Ph.D., Chief Scientific Officer, Coriell Institute for Medical Research

  • CORI – Camden Opioid Reseach Initiative Camden County, NJ – 3 years longitudinal study funded by State of NJ: COriell Institute, Cooper Medical School, NJ Health, Cooper University HC
  1. Prescriptions per 100 persons
  2. overdose death pwe 100,000 persons
  3. US, NJ, Camden, County, NJ
  • 2010 – increase in Prescription
  • 2013 – Synthetic Opioid
  • 2017 – Public health epidemic

THREE ARMS Opiod USE continuum: Exposure __>>> Addiction __>>> Overdose death

  1. OPTIN – Treatment to Pain chronic
  2. GOALS 0 Genomics of Opiod Addiction treatment aptients
  3. BIOBANK – biological samples from deceased aptients: who died of ipiod-related dealth : Saliva, blood, tissue – cellular function & DNA and Stem cells

A. Identify patients at risk

B. Epigenetics

C. drug-drug interaction (combination of drugs – toxicology contribuion to mortality rates

D. Can genetic information be used to study heritability of opioid use disorder

2:30 p.m.
Assessing Progress Toward the Clinical Integration of Personalized Medicine: A Landscape Analysis

Case studies and anecdotal reports suggest that leading academic medical centers and pioneering community health systems have begun to integrate personalized medicine approaches into their clinical work streams. The extent to which health care providers more generally have begun to adopt personalized medicine strategies that go beyond the ordering of genomic sequencing, however, remains unclear.

During this session, Gary Gustavsen, Partner, Managing Director, Health Advances, will share preliminary findings from a PMC-commissioned survey that examined the landscape for the clinical integration of personalized medicine in the U.S. based on a multi-factorial definition of the field. Survey respondents included a geographically diverse set of academic medical centers and community health systems.
» Read More

INTRODUCTION Daryl Pritchard, Ph.D., Senior Vice President, Science Policy, Personalized Medicine Coalition

SPEAKER Gary Gustavsen, Partner, Managing Director, Health Advances

  • Across community hospital systems and Academic, across geographies, across therapeutics areas, across levels of adoption

Part I: Profiling select community health systems

Part II

III

IV Testing Guidance and Data accessibility

V Utilization of Data

VI Data sharing – Inter-institutional not cross institutions

VII Funding

Interviewees were across all functions

ADOPTION ASSESSMENT of Personalized Medicine

  • Collection of genomics data
  • Physician ordering Genomics Testing
2:50 p.m.
The 15th Annual Leadership in Personalized Medicine Award

After accepting the 15th Annual Leadership in Personalized Medicine Award, Genomic Health Chief Scientific Officer Dr. Steven Shak will share his vision for the future of the field with conference attendees.
» Read More

INTRODUCTION | Kimberly Popovits, Chairman of the Board, CEO, President, Genomic Health

  • ex-Genetech: Herceptin, CF therapy
  • Genomic Health – 130 studies

AWARDEE | Steven Shak, M.D., Co-Founder, Chief Scientific Officer, Genomic Health

1986 – Joined Genetech to work on big goals and big ideas

TPA – clinical trials

CF cases – Enzyme clone DNA – tube od sputum inside enzyme – first drug to CF approved in 1997, 30 years a go gene clones

Heceptin – 90% of Breast cancer is treated by – one injected antibody on solid tumor, metastatic BR CA

2000 – Genomic Health was launched 4 out of 100 benefited from chemotherapy

  • Oncotype – can improve care and reduce cost
  • NCI Trial breast cancer 10,000 – 2018 concluded
  • Chemo therapy was transform to a targeted drug – molecular insights
  • Academia, Industry Govenment – no walls – optimally innovate
  • More precision Teamwork, Precision Leadership — NEEDED
  •  Fragmented care
  • Four request: End in mind, few target truth seeking, experiment and continue to learn, be honest with yourself,
  • evemy of innovation is illusion the answer is known
  • loose key changes
  • communitive: inspire others, challenge self and others,
  • Clinical Trials: learn from enrolees

 

3:20 p.m.
Networking Break
4:00 p.m.
Wellness in the Workplace: Understanding the Opportunities and Challenges Associated With Employer-Sponsored Genetic Testing Programs for Healthy Patients

Reasoning that genetic testing may encourage healthy lifestyles by providing information about an employee’s relative risk of developing various diseases, employers seeking to improve patients’ lives and mitigate downstream health care costs have begun to sponsor genetic testing for healthy employees by partnering with various genetic testing companies, some of which sell the tests directly to consumers.

This session, moderated by Quest Diagnostics Chief Medical Officer Dr. Jay G. Wohlgemuth, who is responsible for overseeing health care benefits for Quest’s employees, will spotlight two employer-sponsored genetic testing partnerships and explore the relevant issues. The panel discussion will focus on the significance of information generated from genetic testing, the differences between various genetic testing business models, and the privacy risks associated with the collection of genetic data.
» Read More

MODERATOR | Jay G. Wohlgemuth, M.D., Chief Medical Officer, Senior Vice President, Quest Diagnostics

  • Employers employ Pharmacogenetics, select by polypharmacy
  • Mental Health engagement through employer is problematic

Jane Cheshire Gilbert, C.P.A., Director, Retiree Health Care, Teachers’ Retirement System of Kentucky

  • average 74, 15 prescriptions on average, 65% are 84 years old
  • contain cost for retirees teachers in KY – pool of $$ for medications covered
  • 72% women 28% male
  • 36,000 retirees
  • 64% drug changes due to review following genetic testing 80% of change Medication recommended by Pharmacist was accepted by physicians

Michael Doney, M.D., Ph.D., M.S., Head of Medical Affairs, Color

  • Genetic counseling

Karen E. Knudsen, M.B.A., Ph.D., Executive Vice President, Oncology Services, Jefferson Health; Enterprise Director, Sidney Kimmel Cancer Center at Thomas Jefferson University

  • 36,000 employees all enrolled in

Scott Megill, President, CEO, Coriell Life Sciences

  • Pharmacogenomics
  • provide consultation to patient and physicians
  • Pharmacy team provide services to populations, delivery of medication plan
5:00 p.m.
Preparing Policies: A Keynote Address on the Policy Landscape for Personalized Medicine by Dr. Scott Gottlieb, Resident Fellow, American Enterprise Institute

During this keynote address, former U.S. Food and Drug Administration (FDA) commissioner Dr. Scott Gottlieb will share his thoughts on the evolving policy landscape for personalized medicine.
» Read More

INTRODUCTION Cynthia A. Bens, Senior Vice President, Public Policy, Personalized Medicine Coalition

SPEAKER Scott Gottlieb, M.D., Resident Fellow, American Enterprise Institute

  • create incentives in clinical trial
  • personalized care
  • improve delivery of care
  • Create a new framework for clinical trials
  • cell based therapy to get approval  advanced the frameworkCommon molecular features of a cancer enabling – common backbone change only pathways without the need to recreate the backbone again for another clinical trial
  • site licenses vs individual investigator in need for site license
  • 4 concorsium on this topic
  • innovations on data: data network for post market surveillance
  • Insights on drug safety drug efficacy – model simulation team 35 persons – adoption faster
  • standardize Drug Review: Standard Template vs collections of Drug application process
  • O&D Report tobe standardized
  • legislative solution for diagnostics – laboratory tests and lab-developed tests
  • Digital health tools – slow adoption in context of drug approval drug label put tool into promotional material
  • Taking less risk will affect negatively innovations done by policy in place: Like Gene editing and regenerative medicine vs a small molecule that the biology is well understood
  • Design Part D – premium came lower, specialty drugs, incentives to encorage NEW drugs development like alternative to statins
  • Value delivered to consumers: FDA determination for expeditious approval than coverage need to follow easier to get investment in the development process
  • CMS is setting the ceiling not the floor and its coverage is followed by the entire market size wise
  • DNA data set was EKG on AppleWatch NGS and AI Medical Devices – same approach taken
5:45 p.m.
Closing Remarks

SPEAKER | Edward Abrahams, Ph.D., President, Personalized Medicine Coalition

6:00 p.m.
Welcome Reception at the Isabella Stewart Gardner Museum

 

PART II

Targeting Treatment

8:00 a.m.
Registration and Breakfast

Joseph B. Martin Conference Center at Harvard Medical School
77 Avenue Louis Pasteur, Boston, MA 02115

8:50 a.m.
Opening Remarks

SPEAKER | Stephen L. Eck, M.D., Ph.D., Chief Medical Officer, Immatics US

8:55 a.m.
Welcoming Remarks

SPEAKER | Joseph B. Martin, M.D., Ph.D., Dean Emeritus, Harvard Medical School

Personal story of familial heritage from Europe to Alberta, CA

9:00 a.m.
Going Global: Learning From Governmental Efforts to Advance Personalized Medicine Around the World

Global leaders are working to accelerate an era of personalized medicine around the world by encouraging innovation, modernizing policies, and reforming health systems to speed the clinical adoption of personalized medicine products and services.

During this panel discussion, four governmental representatives will share their visions for the future of personalized medicine and elaborate on their efforts to accelerate progress in the field.
» Read More

MODERATOR | Antonio L. Andreu, M.D., Ph.D., Scientific Director, EATRIS (European Infrastructure for Translational Medicine)

  • Education of the Medical community on genomics and its use in therapy
  • Japan and Denmark are building national sequencing centers

Wadha Al Muftah, M.D., Ph.D., Manager, Clinical Initiatives, Qatar Genome Program

  • 2011BioBank launched as national resource, 20,000 Quataris 3,000 foreigners recruited
  • Interest in the population to understand their Genome for future health
  • Rare disease identified
  • Training & Education in schools about the Genome using comics, Education of Healthcare professionals about Genomics
  • At the University level – Genetic counseling by professionals that understand the culture of patients
  • Precision medicine education for physicians
  • Centralized genomics implementation because the health system is centralized
  • A Pilot study on Cardiovascular Genomics

–>>>>>>>>>> Not attended —<<<<<<<<< Noella Bigirimana, Strategic Advisor, Rwanda Biomedical Center, Ministry of Health, Government of Rwanda; Government Fellow, World Economic Forum

Erja Heikkinen, Ph.D., Deputy Director, General Ministry of Education and Culture, Finland

  • Helsinki – leading cancer research academic center
  • Infrastructure investment in data management and representation of all pharma companies in Finland, all big pharma have offices in Finland
  • English is the language of communication in the research community
  • Three political parties and three ministries
  • Center for Research in Genomic is centralized and is in construction — Research will be following a distributed system of research centers in multiple locations
  • National investment in Genomics like in to other time in the past in any other discipline in Medicine

Raquel Yotti, M.D., Ph.D., General Director, Instituto de Salud Carlos III (Spain)

  • Universal coverage centralized national healthcare system
  • research is national and ministry of Health funds research and integrate it with the health system
  • interaction of clinical application and research studies
  • pharmaco-genomics, genomics testing,
  • challenge – therapies based on genetics and access to all the populations, safety and quality
  • PCPs are a source in the system, network used for systemic change and involve the clinical community including the PCP community
  • International organization under the umbrella of International Personalized medicine – the purpose of Research vs practicing Medicine
  • Government and industry manufacturing cell lines
  • Distribute results of genomics sequencing
10:00 a.m.
Networking Break
10:15 a.m.
Innovation in the Era of Personalized Medicine: A Keynote Conversation With Dr. Paul Stoffels, Chief Scientific Officer, Johnson & Johnson

During this fireside chat with CNBC Reporter Ms. Meg Tirrell, Johnson & Johnson Chief Scientific Officer Dr. Paul Stoffels will help frame the second half of the conference program by sharing the pharmaceutical industry’s perspective on the emerging issues in health care, touching on topics including costs, prices, and access.
» Read More

MODERATOR | Meg Tirrell, Reporter, CNBC

Paul Stoffels, M.D., Vice Chairman, Executive Committee, Chief Scientific Officer, Johnson & Johnson

Goals of medicine in 2019

  • early detection
  • Vaccines in disease prevention
  • Longevity

Challenges

  • Platforms are established, every 20-30 another one emergences
  • access to data – critical platform
  • AI for diagnostics and decision making,
  • biomarkers
  • J&J try to learn on every disease: Lungs and GI
  • Diagnosis, Medical devices,
  • Genomics testing done with diagnosis
  • HIV Vaccine – long development cycle
  • Passion of Scientists
  • pharmaceutics development is based on insights looking into the future – important goal to solve
  • Combination therapy emerges, MOA
  • partnerships: cell therapy can transform cancer treatment

 

10:45 a.m.
Prospecting the Pipeline: Exploring the Implications of a Biopharmaceutical Pipeline Dominated by Personalized Treatments

As researchers develop an enhanced understanding of the molecular causes that underpin various diseases, many biopharmaceutical companies have begun to develop therapies that are targeted to patient subgroups and even personalized to individual patients. In oncology, for example, there are reportedly more than 900 personalized “immunotherapy” treatments being tested in the clinic, with more than 1,000 in preclinical development. The challenging scientific questions and systemic implications associated with these new therapies do not always fit neatly into existing regulatory, payment, and care delivery frameworks.

During this session, CNBC Reporter Ms. Meg Tirrell will moderate a panel discussion that explores the scientific, regulatory, reimbursement, and other systemic issues associated with future gene editing treatments, gene therapies, immunotherapies, and targeted therapies. The panelists, who include industry representatives, a researcher, and an academic leader, will also consider a new approach to immunotherapy for cancer patients in which a unique product is developed for every patient treated.
» Read More

MODERATOR | Meg Tirrell, Reporter, CNBC

Donald L. Siegel, Ph.D., M.D., Director, Division of Transfusion Medicine & Therapeutic Biology, Director, Clinical Cell and Vaccine Production Facility, University of Pennsylvania’s Perelman School of Medicine

  • CAR-T therapy started the Transfusion Medicine & Therapeutic Biology industry
  • no relations explored between Immune T cells and microbiome
  • Cost of CAR-T therapy – use of off the shelf CAR=T cells will lower the proce while it will scale up if no rejection
  • DOGS USED WITH CAR-T TREATMENT OF CANCER IN DOG

 

Harpreet Singh, Ph.D., CEO, Immatics

  • T Cell peptide started 15 years ago Peptonomics,
  • tumors of solid cancer – cell therapies selected from libraries
  1. off the shelf cells from health donors
  2. Biologics bridges tumor cells and solid cells

Paul Stoffels, M.D., Vice Chairman, Executive Committee, Chief Scientific Officer, Johnson & Johnson

  • Impact of Mirobiome it plays a key role in many diseases
  • difficult to develop therapeutics derived from microbiome data
  • Price of Drug support innovations that are transformational need to be valued by society

Alex Vadas, Ph.D., Managing Director, Partner, LEK Consulting

  • TECHNOLOGY TO SELECT COMBINATION THERAPIES

 

11:45 a.m.
Bag Lunch
12:45 p.m.
Balancing Business and Social Objectives to Advance Personalized Medicine: A Case Study of the Dementia Discovery Fund

This interactive case study discussion will explore how and why a group of government agencies, nonprofit organizations, and pharmaceutical companies came together to support the Dementia Discovery Fund, focusing on whether a disease-specific venture that seeks to create meaningful new medicines in part by capitalizing on the evolving science underpinning personalized medicine can successfully balance social and business objectives.
» Read More

MODERATOR | Richard Hamermesh, D.B.A., Co-Faculty Chair, Harvard Business School Kraft Precision Medicine Accelerator

1:45 p.m.
Toward a Shared Value Proposition in Health Care: Pursuing Value-Based Solutions in Research, Regulation, Reimbursement, and Clinical Adoption

To advance the principles of personalized medicine, the field’s proponents will need to align representatives from multiple sectors of the health system on a shared value proposition that recognizes the importance of addressing the shortcomings of one-size-fits-all medicine.

During this session, M2Gen Executive Chairman Dr. William S. Dalton will convene a commercial payer, an industry representative, a patient, and a value assessment framework developer to explore research, regulatory, clinical adoption, and especially reimbursement solutions that will, in the interest of patients, advance the principles of personalized medicine.
» Read More

MODERATOR | William S. Dalton, Ph.D., M.D., Executive Chairman, M2Gen

Bonnie J. Addario, Co-Founder, Chair, GO2 Foundation for Lung Cancer

Sarah K. Emond, Executive Vice President, Chief Operating Officer, Institute for Clinical and Economic Review

Anne-Marie Martin, Ph.D., Senior Vice President, Global Head of Precision Medicine, Novartis Pharmaceuticals Corporation

Michael Sherman, M.D., Chief Medical Officer, Senior Vice President, Harvard Pilgrim Health Care

2:45 p.m.
Closing Remarks

SPEAKER | Edward Abrahams, Ph.D., President, Personalized Medicine Coalition

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scPopCorn: A New Computational Method for Subpopulation Detection and their Comparative Analysis Across Single-Cell Experiments

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Present day technological advances have facilitated unprecedented opportunities for studying biological systems at single-cell level resolution. For example, single-cell RNA sequencing (scRNA-seq) enables the measurement of transcriptomic information of thousands of individual cells in one experiment. Analyses of such data provide information that was not accessible using bulk sequencing, which can only assess average properties of cell populations. Single-cell measurements, however, can capture the heterogeneity of a population of cells. In particular, single-cell studies allow for the identification of novel cell types, states, and dynamics.

 

One of the most prominent uses of the scRNA-seq technology is the identification of subpopulations of cells present in a sample and comparing such subpopulations across samples. Such information is crucial for understanding the heterogeneity of cells in a sample and for comparative analysis of samples from different conditions, tissues, and species. A frequently used approach is to cluster every dataset separately, inspect marker genes for each cluster, and compare these clusters in an attempt to determine which cell types were shared between samples. This approach, however, relies on the existence of predefined or clearly identifiable marker genes and their consistent measurement across subpopulations.

 

Although the aligned data can then be clustered to reveal subpopulations and their correspondence, solving the subpopulation-mapping problem by performing global alignment first and clustering second overlooks the original information about subpopulations existing in each experiment. In contrast, an approach addressing this problem directly might represent a more suitable solution. So, keeping this in mind the researchers developed a computational method, single-cell subpopulations comparison (scPopCorn), that allows for comparative analysis of two or more single-cell populations.

 

The performance of scPopCorn was tested in three distinct settings. First, its potential was demonstrated in identifying and aligning subpopulations from single-cell data from human and mouse pancreatic single-cell data. Next, scPopCorn was applied to the task of aligning biological replicates of mouse kidney single-cell data. scPopCorn achieved the best performance over the previously published tools. Finally, it was applied to compare populations of cells from cancer and healthy brain tissues, revealing the relation of neoplastic cells to neural cells and astrocytes. Consequently, as a result of this integrative approach, scPopCorn provides a powerful tool for comparative analysis of single-cell populations.

 

This scPopCorn is basically a computational method for the identification of subpopulations of cells present within individual single-cell experiments and mapping of these subpopulations across these experiments. Different from other approaches, scPopCorn performs the tasks of population identification and mapping simultaneously by optimizing a function that combines both objectives. When applied to complex biological data, scPopCorn outperforms previous methods. However, it should be kept in mind that scPopCorn assumes the input single-cell data to consist of separable subpopulations and it is not designed to perform a comparative analysis of single cell trajectories datasets that do not fulfill this constraint.

 

Several innovations developed in this work contributed to the performance of scPopCorn. First, unifying the above-mentioned tasks into a single problem statement allowed for integrating the signal from different experiments while identifying subpopulations within each experiment. Such an incorporation aids the reduction of biological and experimental noise. The researchers believe that the ideas introduced in scPopCorn not only enabled the design of a highly accurate identification of subpopulations and mapping approach, but can also provide a stepping stone for other tools to interrogate the relationships between single cell experiments.

 

References:

 

https://www.sciencedirect.com/science/article/pii/S2405471219301887

 

https://www.tandfonline.com/doi/abs/10.1080/23307706.2017.1397554

 

https://ieeexplore.ieee.org/abstract/document/4031383

 

https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0927-y

 

https://www.sciencedirect.com/science/article/pii/S2405471216302666

 

 

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First Cost-Effectiveness Study of Multi-Gene Panel Sequencing in Advanced Non-Small Cell Lung Cancer Shows Moderate Cost-Effectiveness, Exposes Crucial Practice Gap

WASHINGTON (June 27, 2019) — The results of the first economic modeling study to estimate the cost-effectiveness of “multi-gene panel sequencing” (MGPS) as compared to standard-of-care, single-gene tests for patients with advanced non-small cell lung cancer (aNSCLC) show that the MGPS tests are moderately cost-effective but could deliver more value if patients with test results identifying actionable genetic mutations consistently received genetically guided treatments. The results of the study, which was commissioned by the Personalized Medicine Coalition (PMC), underline the need to align clinical practices with an era of personalized medicine in which physicians can use diagnostic tests to identify specific biological markers that inform targeted prevention and treatment plans.

The study, which was published yesterday in JCO Clinical Cancer Informatics, analyzed the clinical and economic value of using MGPS testing to identify patients with tumors that over-express genetic mutations that could be targeted by available therapies designed to inhibit the function of those genes — a mainstay of modern care for aNSCLC patients. Using data provided by Flatiron Health, researchers examined clinical and cost information associated with the care of 5,688 patients with aNSCLC treated between 2011 – 2016, separating them into cohorts who received MGPS tests that assess at least 30 genetic mutations at once and those who received only “single-marker genetic testing” (SMGT) of less than 30 genes.

Compared to SMGT, the MGPS testing strategy, including downstream treatment and monitoring of disease, incurred costs equal to $148,478 for each year of life that it facilitated, a level suggesting that MGPS is moderately cost-effective compared to commonly cited thresholds in the U.S., which range from $50,000 to $200,000 per life year (LY) gained.

The authors of the study point out, however, that physicians only prescribed a targeted therapy to some of the patients whose MGPS test results revealed actionable mutations. MGPS tests can only improve downstream patient outcomes if actionable results are used to put the patient on a targeted treatment regimen that is more effective than the therapy they would otherwise have been prescribed. It is therefore impossible for the cost of an MGPS test to translate into additional LYs if actionable results do not result in the selection of a targeted treatment regimen.

Although MGPS testing revealed actionable mutations in 30.1 percent of the patients in the study cohort, only 21.4 percent of patients who underwent MGPS testing received a targeted treatment.

The study’s authors calculated that if all MGPS-tested patients with actionable mutations had received a targeted therapy, MGPS testing would deliver measurably better value ($110,000 per LY gained).

“This research underlines the importance of ensuring that clinical practices keep pace with scientific progress in personalized medicine so that we can maximize the benefits of diagnostic tests that can improve patient care and make the health system more efficient by ensuring that safe and effective targeted therapies are prescribed to those patients who will benefit,” said PMC President Edward Abrahams.

The study’s authors include Dr. Lotte Steuten, Vice President and Head of Consulting, The Office of Health Economics, London, U.K., and Affiliate Associate Faculty Member, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center; Dr. Bernardo Goulart, Associate Faculty Member, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center; Dr. Neal Meropol, Vice President, Research Oncology, Flatiron Health; Dr. Daryl Pritchard, Senior Vice President, Science Policy, Personalized Medicine Coalition; and Dr. Scott Ramsey, Director, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center.

###

About the Personalized Medicine Coalition:

The Personalized Medicine Coalition, representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system. For more information, please visit www.personalizedmedicinecoalition.org.

SOURCE

From: Personalized Medicine Coalition <pmc@personalizedmedicinecoalition.org>

Reply-To: “Christopher Wells (PMC)” <cwells@personalizedmedicinecoalition.org>

Date: Thursday, June 27, 2019 at 9:32 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: First Cost-Effectiveness Study of MGPS in aNSCLC Shows Moderate Cost-Effectiveness, Exposes Crucial Practice Gap

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