Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
AI will help reduce time for drug development especially in early phase of discovery but eventually help in all phases
Ganhui: for drug regulators might be more amenable to AI in clinical trials; AI may be used differently by clinicians
nonprofit in Philadelphia using AI to repurpose drugs (this site has posted on this and article will be included here)
Ganhui: top challenge of AI in Pharma; rapid evolution of AI and have to have core understanding of your needs and dependencies; realistic view of what can be done; AI has to have iterative learning; also huge vertical challenge meaning how can we allign the use of AI through the healthcare vertical layer chain like clinicians, payers, etc.
Ganhui sees a challenge for health companies to understand how to use AI in business to technology; AI in AI companies is different need than AI in healthcare companies
95% of AI projects not successful because most projects are very discrete use
2:00-2:20
Building Precision Oncology Infrastructure in Low- and Middle-Income Countries
globally 60 precision initiatives but there really are because many in small countries
three out of five individuals in India die of cancer
precision medicine is a must and a hub and spoke model is needed in these places; Italy does this hub and spoke; spokes you enable the small places and bring them into the network so they know how and have access to precision medicine
in low income countries the challenge starts with biopsy: then diagnosis and biomarker is issue; then treatment decision a problem as they may not have access to molecular tumor boards
prevention is always a difficult task in LMICs (low income)
you have ten times more patients in India than in US (triage can be insurmountable)
ICGA Foundation: Indian Cancer Genome Atlas
in India mutational frequencies vary with geographical borders like EGFR mutations or KRAS mutations
genomic landscape of ovarian cancer in India totally different than in TCGA data
even different pathways are altered in ovarian cancer seen in North America than in India
MAY mean that biomarker panels need to be adjusted based on countries used in
the molecular data has to be curated for the India cases to be submitted to a tumor board
twenty diagnostic tests in market like TruCheck for Indian market; uses liquid biopsy
they are also tailoring diagnostic and treatment for India getting FDA fast track approvals
2:20-2:40
Co-targeting KIT/PDGRFA and Genomic Integrity in Gastrointestinal Stromal Tumors
Lori Rink, PhD, Associate Professor, Fox Chase Cancer Center
GIST are most common nesychymal tumor in GI tract
used to be misdiagnosed; was considered a leimyosarcoma
very asymptomatic tumors and not good prognosis
very refractory to genotoxic therapies
RTK KIT/PDGFRA gain of function mutations
Gleevec imatinib for unresectable GIST however vast majority of even responders become resistant to therapy and cancer returns
there is a mutation map for hotspot mutations and sensitivity for gleevec
however resistance emerged to ripretinib; in ATP binding pocket
over treatment get a polyclonal resistance
performed a kinome analysis; Wee1 looked like a potential target
mouse studies (80 day) showed good efficacy
avapiritinib ahs some neurotox and used in PDGFRA mut GIST model which is resistant to imitinib
but if use Wee1 inhibitor with TKI can lower dose of avapiritinib
cotargeting KIT/PDGFRA and WEE1 increases replicative stress
they are using PDX models to test these combinations
Shaping the Future: The Rise of Structural Nanomedicine
Curator: Dr. Sudipta Saha, Ph.D.
In their 2025 review, Mirkin, Mrksich, and Artzi describe how the field of structural nanomedicine is being transformed to revolutionize biomedical science. Therapeutic materials are now being designed with precise nanoscale architectures to optimize biological interactions, improve efficacy, and reduce side effects.
It is explained that, unlike traditional drug delivery methods, structural nanomedicine is centered on the engineering of form and function at the molecular level. Advances in DNA and RNA nanotechnology, self-assembling peptide systems, and engineered nanoparticles have been utilized to create customizable platforms capable of navigating complex biological environments. These structures are being programmed to respond to specific physiological triggers, thereby enabling targeted delivery and controlled release.
A strong emphasis is placed on how rational design principles—borrowed from materials science, chemistry, and bioengineering—are driving innovation. Examples are presented where precisely constructed nanostructures have been shown to outperform conventional therapies in cancer treatment, immunomodulation, and regenerative medicine.
Attention is drawn to the challenges that must still be addressed, including the scalability of manufacturing, regulatory barriers, and the need for deeper insights into nano-bio interactions at the systems level. It is argued that interdisciplinary collaboration will be required for the successful translation of structural nanomedicine from laboratory research to clinical application.
Ultimately, structural nanomedicine is portrayed as a paradigm shift—where passive carrier systems are being replaced by dynamic, functional architectures that actively engage in therapeutic processes. Optimism is expressed that through continued technological convergence, a new generation of precision therapies tailored to individual patients will be realized.
This review is recommended for researchers, clinicians, and industry professionals seeking to remain informed about future directions in biomedical innovation.
From: Heidi Rheim et al. GA4GH: International policies and standards for data sharing across genomic research and healthcare. (2021): Cell Genomics, Volume 1 Issue 2.
Siloing genomic data in institutions/jurisdictions limits learning and knowledge
GA4GH policy frameworks enable responsible genomic data sharing
GA4GH technical standards ensure interoperability, broad access, and global benefits
Data sharing across research and healthcare will extend the potential of genomics
Summary
The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.
In order for genomic and personalized medicine to come to fruition it is imperative that data siloes around the world are broken down, allowing the international collaboration for the collection, storage, transferring, accessing and analying of molecular and health-related data.
We had talked on this site in numerous articles about the problems data siloes produce. By data siloes we are meaning that collection and storage of not only DATA but intellectual thought are being held behind physical, electronic, and intellectual walls and inacessible to other scientisits not belonging either to a particular institituion or even a collaborative network.
Standardization and harmonization of data is key to this effort to sharing electronic records. The EU has taken bold action in this matter. The following section is about the General Data Protection Regulation of the EU and can be found at the following link:
The data protection package adopted in May 2016 aims at making Europe fit for the digital age. More than 90% of Europeans say they want the same data protection rights across the EU and regardless of where their data is processed.
The General Data Protection Regulation (GDPR)
Regulation (EU) 2016/679 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data. This text includes the corrigendum published in the OJEU of 23 May 2018.
The regulation is an essential step to strengthen individuals’ fundamental rights in the digital age and facilitate business by clarifying rules for companies and public bodies in the digital single market. A single law will also do away with the current fragmentation in different national systems and unnecessary administrative burdens.
Directive (EU) 2016/680 on the protection of natural persons regarding processing of personal data connected with criminal offences or the execution of criminal penalties, and on the free movement of such data.
The directive protects citizens’ fundamental right to data protection whenever personal data is used by criminal law enforcement authorities for law enforcement purposes. It will in particular ensure that the personal data of victims, witnesses, and suspects of crime are duly protected and will facilitate cross-border cooperation in the fight against crime and terrorism.
The directive entered into force on 5 May 2016 and EU countries had to transpose it into their national law by 6 May 2018.
The following paper by the organiztion The Global Alliance for Genomics and Health discusses these types of collaborative efforts to break down data silos in personalized medicine. This organization has over 2000 subscribers in over 90 countries encompassing over 60 organizations.
Enabling responsible genomic data sharing for the benefit of human health
The Global Alliance for Genomics and Health (GA4GH) is a policy-framing and technical standards-setting organization, seeking to enable responsible genomic data sharing within a human rights framework.
he Global Alliance for Genomics and Health (GA4GH) is an international, nonprofit alliance formed in 2013 to accelerate the potential of research and medicine to advance human health. Bringing together 600+ leading organizations working in healthcare, research, patient advocacy, life science, and information technology, the GA4GH community is working together to create frameworks and standards to enable the responsible, voluntary, and secure sharing of genomic and health-related data. All of our work builds upon the Framework for Responsible Sharing of Genomic and Health-Related Data.
GA4GH Connect is a five-year strategic plan that aims to drive uptake of standards and frameworks for genomic data sharing within the research and healthcare communities in order to enable responsible sharing of clinical-grade genomic data by 2022. GA4GH Connect links our Work Streams with Driver Projects—real-world genomic data initiatives that help guide our development efforts and pilot our tools.
The Global Alliance for Genomics and Health (GA4GH) is a worldwide alliance of genomics researchers, data scientists, healthcare practitioners, and other stakeholders. We are collaborating to establish policy frameworks and technical standards for responsible, international sharing of genomic and other molecular data as well as related health data. Founded in 2013,3 the GA4GH community now consists of more than 1,000 individuals across more than 90 countries working together to enable broad sharing that transcends the boundaries of any single institution or country (see https://www.ga4gh.org).In this perspective, we present the strategic goals of GA4GH and detail current strategies and operational approaches to enable responsible sharing of clinical and genomic data, through both harmonized data aggregation and federated approaches, to advance genomic medicine and research. We describe technical and policy development activities of the eight GA4GH Work Streams and implementation activities across 24 real-world genomic data initiatives (“Driver Projects”). We review how GA4GH is addressing the major areas in which genomics is currently deployed including rare disease, common disease, cancer, and infectious disease. Finally, we describe differences between genomic sequence data that are generated for research versus healthcare purposes, and define strategies for meeting the unique challenges of responsibly enabling access to data acquired in the clinical setting.
GA4GH organization
GA4GH has partnered with 24 real-world genomic data initiatives (Driver Projects) to ensure its standards are fit for purpose and driven by real-world needs. Driver Projects make a commitment to help guide GA4GH development efforts and pilot GA4GH standards (see Table 2). Each Driver Project is expected to dedicate at least two full-time equivalents to GA4GH standards development, which takes place in the context of GA4GH Work Streams (see Figure 1). Work Streams are the key production teams of GA4GH, tackling challenges in eight distinct areas across the data life cycle (see Box 1). Work Streams consist of experts from their respective sub-disciplines and include membership from Driver Projects as well as hundreds of other organizations across the international genomics and health community.
Figure 1Matrix structure of the Global Alliance for Genomics and HealthShow full caption
Box 1GA4GH Work Stream focus areasThe GA4GH Work Streams are the key production teams of the organization. Each tackles a specific area in the data life cycle, as described below (URLs listed in the web resources).
(1)Data use & researcher identities: Develops ontologies and data models to streamline global access to datasets generated in any country9,10
(2)Genomic knowledge standards: Develops specifications and data models for exchanging genomic variant observations and knowledge18
(3)Cloud: Develops federated analysis approaches to support the statistical rigor needed to learn from large datasets
(4)Data privacy & security: Develops guidelines and recommendations to ensure identifiable genomic and phenotypic data remain appropriately secure without sacrificing their analytic potential
(5)Regulatory & ethics: Develops policies and recommendations for ensuring individual-level data are interoperable with existing norms and follow core ethical principles
(6)Discovery: Develops data models and APIs to make data findable, accessible, interoperable, and reusable (FAIR)
(7)Clinical & phenotypic data capture & exchange: Develops data models to ensure genomic data is most impactful through rich metadata collected in a standardized way
(8)Large-scale genomics: Develops APIs and file formats to ensure harmonized technological platforms can support large-scale computing
For more articles on Open Access, Science 2.0, and Data Networks for Genomics on this Open Access Scientific Journal see:
#TUBiol5227: Biomarkers & Biotargets: Genetic Testing and Bioethics
Curator: Stephen J. Williams, Ph.D.
The advent of direct to consumer (DTC) genetic testing and the resultant rapid increase in its popularity as well as companies offering such services has created some urgent and unique bioethical challenges surrounding this niche in the marketplace. At first, most DTC companies like 23andMe and Ancestry.com offered non-clinical or non-FDA approved genetic testing as a way for consumers to draw casual inferences from their DNA sequence and existence of known genes that are linked to disease risk, or to get a glimpse of their familial background. However, many issues arose, including legal, privacy, medical, and bioethical issues. Below are some articles which will explain and discuss many of these problems associated with the DTC genetic testing market as well as some alternatives which may exist.
As you can see,this market segment appears to want to expand into the nutritional consulting business as well as targeted biomarkers for specific diseases.
Rising incidence of genetic disorders across the globe will augment the market growth
Increasing prevalence of genetic disorders will propel the demand for direct-to-consumer genetic testing and will augment industry growth over the projected timeline. Increasing cases of genetic diseases such as breast cancer, achondroplasia, colorectal cancer and other diseases have elevated the need for cost-effective and efficient genetic testing avenues in the healthcare market.
For instance, according to the World Cancer Research Fund (WCRF), in 2018, over 2 million new cases of cancer were diagnosed across the globe. Also, breast cancer is stated as the second most commonly occurring cancer. Availability of superior quality and advanced direct-to-consumer genetic testing has drastically reduced the mortality rates in people suffering from cancer by providing vigilant surveillance data even before the onset of the disease. Hence, the aforementioned factors will propel the direct-to-consumer genetic testing market overt the forecast timeline.
Nutrigenomic Testing will provide robust market growth
The nutrigenomic testing segment was valued over USD 220 million market value in 2019 and its market will witness a tremendous growth over 2020-2028. The growth of the market segment is attributed to increasing research activities related to nutritional aspects. Moreover, obesity is another major factor that will boost the demand for direct-to-consumer genetic testing market.
Nutrigenomics testing enables professionals to recommend nutritional guidance and personalized diet to obese people and help them to keep their weight under control while maintaining a healthy lifestyle. Hence, above mentioned factors are anticipated to augment the demand and adoption rate of direct-to-consumer genetic testing through 2028.
Browse key industry insights spread across 161 pages with 126 market data tables & 10 figures & charts from the report, “Direct-To-Consumer Genetic Testing Market Size By Test Type (Carrier Testing, Predictive Testing, Ancestry & Relationship Testing, Nutrigenomics Testing), By Distribution Channel (Online Platforms, Over-the-Counter), By Technology (Targeted Analysis, Single Nucleotide Polymorphism (SNP) Chips, Whole Genome Sequencing (WGS)), Industry Analysis Report, Regional Outlook, Application Potential, Price Trends, Competitive Market Share & Forecast, 2020 – 2028” in detail along with the table of contents: https://www.gminsights.com/industry-analysis/direct-to-consumer-dtc-genetic-testing-market
Targeted analysis techniques will drive the market growth over the foreseeable future
Based on technology, the DTC genetic testing market is segmented into whole genome sequencing (WGS), targeted analysis, and single nucleotide polymorphism (SNP) chips. The targeted analysis market segment is projected to witness around 12% CAGR over the forecast period. The segmental growth is attributed to the recent advancements in genetic testing methods that has revolutionized the detection and characterization of genetic codes.
Targeted analysis is mainly utilized to determine any defects in genes that are responsible for a disorder or a disease. Also, growing demand for personalized medicine amongst the population suffering from genetic diseases will boost the demand for targeted analysis technology. As the technology is relatively cheaper, it is highly preferred method used in direct-to-consumer genetic testing procedures. These advantages of targeted analysis are expected to enhance the market growth over the foreseeable future.
Over-the-counter segment will experience a notable growth over the forecast period
The over-the-counter distribution channel is projected to witness around 11% CAGR through 2028. The segmental growth is attributed to the ease in purchasing a test kit for the consumers living in rural areas of developing countries. Consumers prefer over-the-counter distribution channel as they are directly examined by regulatory agencies making it safer to use, thereby driving the market growth over the forecast timeline.
Favorable regulations provide lucrative growth opportunities for direct-to-consumer genetic testing
Europe direct-to-consumer genetic testing market held around 26% share in 2019 and was valued at around USD 290 million. The regional growth is due to elevated government spending on healthcare to provide easy access to genetic testing avenues. Furthermore, European regulatory bodies are working on improving the regulations set on the direct-to-consumer genetic testing methods. Hence, the above-mentioned factors will play significant role in the market growth.
Focus of market players on introducing innovative direct-to-consumer genetic testing devices will offer several growth opportunities
Few of the eminent players operating in direct-to-consumer genetic testing market share include Ancestry, Color Genomics, Living DNA, Mapmygenome, Easy DNA, FamilytreeDNA (Gene By Gene), Full Genome Corporation, Helix OpCo LLC, Identigene, Karmagenes, MyHeritage, Pathway genomics, Genesis Healthcare, and 23andMe. These market players have undertaken various business strategies to enhance their financial stability and help them evolve as leading companies in the direct-to-consumer genetic testing industry.
For example, in November 2018, Helix launched a new genetic testing product, DNA discovery kit, that allows customer to delve into their ancestry. This development expanded the firm’s product portfolio, thereby propelling industry growth in the market.
The following posts discuss bioethical issues related to genetic testing and personalized medicine from a clinicians and scientisit’s perspective
Question:Each of these articles discusses certain bioethical issues although focuses on personalized medicine and treatment. Given your understanding of the robust process involved in validating clinical biomarkers and the current state of the DTC market, how could DTC testing results misinform patients and create mistrust in the physician-patient relationship?
Question: If you are developing a targeted treatment with a companion diagnostic, what bioethical concerns would you address during the drug development process to ensure fair, equitable and ethical treatment of all patients, in trials as well as post market?
Articles on Genetic Testing, Companion Diagnostics and Regulatory Mechanisms
Question: What type of regulatory concerns should one have during the drug development process in regards to use of biomarker testing?From the last article on Protecting Your IP how important is it, as a drug developer, to involve all payers during the drug development process?
Recognizing that almost 40 percent of those who responded to the strategic planning survey underpinning the plan did not agree that “it is inevitable that all doctors will someday practice personalized medicine [because] the science and technology will demand it,” the Coalition has outlined robust efforts to encourage and nurture medical progress through education, advocacy, and evidence development.On behalf of the Personalized Medicine Coalition (PMC), I am pleased to share PMC’s Strategic Plan for 2019.
Unless payers, providers, patients, and policymakers are aware of personalized medicine, it will be harder to increase research funding and propose smart public policies that encourage integrating diagnostics into therapeutic decisions.
And unless we develop the evidence base necessary to demonstrate the clinical and economic value of personalized medicine, those decision-makers are not going to embrace it, and, in fact, may propose policies, like “step therapy” — paying for what costs least first — that fly in the face of the principles of personalized medicine.
In short, in keeping with the scientific and technological progress of recent years, we need to redouble our efforts to deliver the promise of personalized medicine — better clinical outcomes and more efficient health systems. The stakes are very high.
We welcome your participation in PMC this year. Without it, progress will be much slower than any of us would like.
Please contact PMC Membership & Development Director Kayla Smith at ksmith@personalizedmedicinecoalition.org with questions about how to get involved with any of the projects listed in the plan.
Role of Informatics in Precision Medicine: Notes from Boston Healthcare Webinar: Can It Drive the Next Cost Efficiencies in Oncology Care? Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)
Role of Informatics in Precision Medicine: Notes from Boston Healthcare Webinar: Can It Drive the Next Cost Efficiencies in Oncology Care?
Reporter: Stephen J. Williams, Ph.D.
Boston Healthcare sponsored a Webinar recently entitled ” Role of Informatics in Precision Medicine: Implications for Innovators”. The webinar focused on the different informatic needs along the Oncology Care value chain from drug discovery through clinicians, C-suite executives and payers. The presentation, by Joseph Ferrara and Mark Girardi, discussed the specific informatics needs and deficiencies experienced by all players in oncology care and how innovators in this space could create value. The final part of the webinar discussed artificial intelligence and the role in cancer informatics.
Below is the mp4 video and audio for this webinar. Notes on each of the slides with a few representative slides are also given below:
Please click below for the mp4 of the webinar:
worldwide oncology related care to increase by 40% in 2020
big movement to participatory care: moving decision making to the patient. Need for information
cost components focused on clinical action
use informatics before clinical stage might add value to cost chain
Key unmet needs from perspectives of different players in oncology care where informatics may help in decision making
Needs of Clinicians
– informatic needs for clinical enrollment
– informatic needs for obtaining drug access/newer therapies
2. Needs of C-suite/health system executives
– informatic needs to help focus of quality of care
– informatic needs to determine health outcomes/metrics
3. Needs of Payers
– informatic needs to determine quality metrics and managing costs
– informatics needs to form guidelines
– informatics needs to determine if biomarkers are used consistently and properly
– population level data analytics
What are the kind of value innovations that tech entrepreneurs need to create in this space? Two areas/problems need to be solved.
innovations in data depth and breadth
need to aggregate information to inform intervention
Different players in value chains have different data needs
Data Depth: Cumulative Understanding of disease
Data Depth: Cumulative number of oncology transactions
technology innovators rely on LEGACY businesses (those that already have technology) and these LEGACY businesses either have data breath or data depth BUT NOT BOTH; (IS THIS WHERE THE GREATEST VALUE CAN BE INNOVATED?)
NEED to provide ACTIONABLE as well as PHENOTYPIC/GENOTYPIC DATA
data depth more important in clinical setting as it drives solutions and cost effective interventions. For example Foundation Medicine, who supplies genotypic/phenotypic data for patient samples supplies high data depth
technologies are moving to data support
evidence will need to be tied to umbrella value propositions
Informatic solutions will have to prove outcome benefit
How will Machine Learning be involved in the healthcare value chain?
increased emphasis on real time datasets – CONSTANT UPDATES NEED TO OCCUR. THIS IS NOT HAPPENING BUT VALUED BY MANY PLAYERS IN THIS SPACE
Interoperability of DATABASES Important! Many Players in this space don’t understand the complexities integrating these datasets
Other Articles on this topic of healthcare informatics, value based oncology, and healthcare IT on this OPEN ACCESS JOURNAL include:
LIVE eProceedings Day Two – The 14th Annual Personalized Medicine Conference: The Business of Personalization, November 15, 2018, HMS, Boston
Real Time Coverage: Aviva Lev-Ari, PhD, RN
PART II
The Business of Personalization
“The successful implementation of [personalized medicine] will depend on the embrace of [its] principles in the business community.”
—RAJU KUCHERLAPATI, PH.D.
Paul C. Cabot Professor of Genetics, Harvard Medical School
*** Speakers will be added to the schedule on a rolling basis as they are confirmed. ***
7:00 a.m.
Registration and Continental Breakfast
Joseph B. Martin Conference Center at Harvard Medical School 77 Avenue Louis Pasteur, Boston, MA 02115
8:00 a.m.
Opening Remarks
SPEAKER | Stephen L. Eck, M.D., Ph.D., Chief Medical Officer, Immatics U.S. Inc; Board Chair, Personalized Medicine Coalition
8:10 a.m.
Pioneering Precision: Inside the Pharmaceutical Industry’s Push Toward Personalized Medicine — A Fireside Chat
MODERATOR | Meg Tirrell, Reporter, CNBC
Daniel O’Day, CEO, Roche Pharmaceuticals
8:55 a.m.
Considering Costs: Evaluating Emerging Pharmaceutical and Insurance Industry Business Models in Personalized Medicine
The pharmaceutical industry is deeply invested in commercializing personalized therapies that must recoup fixed development costs from smaller patient populations covered by health insurance companies that are increasingly concerned about rising health care costs. In that context, this diverse panel will explore the viability of the business model for developing and paying for personalized medicines, tackling issues related to costs, prices, and access.
MODERATOR | Meg Tirrell, Reporter, CNBC
Peter Juhn, M.D., M.P.H., Global Head of Value-Based Partnerships, Amgen
Nick Leschly, CEO, Bluebird Bio
Michael Sherman, M.D., Chief Medical Officer, Senior Vice President, Harvard Pilgrim Health Care
Sean Tunis, M.D., Founder, CEO, Center for Medical Technology Policy
9:55 a.m.
Networking Break
Light refreshments provided.
Sponsored By
10:25 a.m.
Reinventing Research: Are Adaptive Platform Trials the Model of the Future? (A Harvard Business School Case Study)
Recognizing that traditional randomized controlled clinical trials can only study the safety and efficacy of a single therapy in one large population of patients, researchers in personalized medicine increasingly hope that “adaptive platform trials,” which employ advanced statistical techniques to simultaneously test the effectiveness of several personalized treatments in multiple sub-populations of patients, may be the key to new drug approvals in the future. Adaptive platform trials may make drug development more efficient by revealing which of several drug candidates are most promising for which patients, but maximizing the potential of these trials requires unprecedented collaboration among the institutions conducting and sponsoring research on various personalized treatments — and no obvious business models have emerged.
During this interactive case study discussion, professors from Harvard Business School will help us examine how researchers at the Dana-Farber Cancer Institute considered and addressed myriad challenges in their effort to design and operationalize an adaptive platform trial for glioblastoma patients, a deadly disease state for which there are few existing treatment options.
PRESENTED BY
Richard Hamermesh, D.B.A., Co-Faculty Chair, Harvard Business School Kraft Precision Medicine Accelerator; and
Ariel D. Stern, Ph.D., Assistant Professor, Technology and Operations Management Unit, Harvard Business School
11:40 a.m.
The 14th Annual Leadership in Personalized Medicine Award
INTRODUCTION | Steven D. Averbuch, M.D., Vice President, Head of Precision Medicine, Bristol-Myers Squibb
Ellen V. Sigal head of Friends of Cancer Research
Advanced science by Diagnostics Tests
Cancer Moonshot Program
Revolution therapies brought to market by Sigel’s sponsorship
AWARDEE | Ellen V. Sigal, Ph.D., Chairperson, Founder, Friends of Cancer Research
Friendly conversation:
Thanks to PMC
sister die on breast cancer at 40 with child of 4 1/2.
appointed to celebrate 20th year of American Cancer Association – Funding for Research, money spend in Washington is for Patients.
After ten years, interested in measurement of achieving evaluation, FDA structure was of interest.
Precision Medicine: biomarkers and targets for patients to define success for each patient, WHat is the right population for any drug, responders to drug therapy, if no response, change the drug.
Patient perspective: Challenges: 90% are treated in the Community and they need a second opinion, insurance, access, clinical trials done out of the community in Academic hospitals – patients are scared to death. Patients are asking for options: Right testing, access to testing involve insurance
combination therapy – 6-8 months in advance,
12:10 p.m.
Bag Lunch
1:10 p.m.
Predicting and Preventing: Evaluating Progress Toward Personalized Medicine
The original architects of the personalized medicine paradigm envisioned an era in which clinicians could predict, prevent and treat disease based on an improved understanding of how human biology interacts with external environments. During this session, a panel of experts will examine our progress on each of these fronts during a wide-ranging conversation about personalized medicine’s past, present and future.
MODERATOR | Cynthia Casson Morton, Ph.D., William Lambert Richardson Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School
1 Million volunteer participants for genome sequencing and microbiome data
PM Past, Present and Future
Issues that are rapidly evolving: Physician, Patients
Birgit Funke, Ph.D., F.A.C.M.G., Vice President, Clinical Affairs, Veritas Genetics; Associate Professor of Pathology (Part-Time), Harvard Medical School
Risk prevention,
driving DOWN operating cost curation of the Genome
Luba Greenwood, J.D., Strategic Business Development and Corporate Ventures, Verily (an Alphabet company)
view on diagnostics from Roche, CHemist and lawyer, Venture capital, beyond Genomics, from diagnosis to prognosis,at Verily projects tapping into the entire life span aspect of health
treatment solution therapeutics except og Oncology threatment is a strugle in the genomics field and pharmaco-genomics
Power the patients vs Genomics in Diabetes
Diagnostics in use to keep patients OUT of hospitals – management of chronic diseases
Patient need to own the genome data not a Databank
Keith Stewart, M.B., CH.B., Carlson and Nelson Endowed Director, Center for Individualized Medicine, Mayo Clinic
Hematologist, genomics apply genomics for detection of predisposition, inherited , Health genome sequencing,
Barriers to deploy genomics: Knowledge, readiness of providers, cost of uninsured,
Diagnostics high value low cost
drug adherence, pharmacists to be involved in drug adherence before refill
2:10 p.m.
Assessing the Assays: Determining the Clinical and Economic Utility of Genomic Sequencing
Advocates for personalized medicine have contended that genomic sequencing can deliver clinical and economic value to patients and the health system by allowing providers to more efficiently diagnose disease and develop treatment plans. Following increased use of genomic sequencing in clinical settings, many stakeholders, including payers, have begun to examine that value proposition more closely. During this session, a pharmaceutical industry representative, a payer, and a health economist will discuss the status and future of the emerging evidence regarding the clinical and economic utility of genomic sequencing, including studies recently commissioned by the Personalized Medicine Coalition.
MODERATOR | Daryl Pritchard, Ph.D., Senior Vice President, Science Policy, Personalized Medicine Coalition
genetic profiling, adopt policy and procedures for mass deployment of NGS
show that it works – demonstrate value, payers and providers
a little more that evidence exist for payer to cover
rare diagnosed disease
Kristine Bordenave, M.D., F.A.C.P., Corporate Medical Director, Humana
labs, payers, providers, pharma — the GAP to be bridged
opportunities to prevent and treat disease
Payer, MDs, cost and impact, markers,
Humana has a research division Use Testing to find value, pharmacogenomics – on Medicare, Medicaid patients
cost of doing the test vs not doing this test – assess value
pharmacisit, economist, statisticians – CMS – provide data on what is covered and what is not Humana: any missed opportunities, MD order tests of no impact per medical record
What test needed to be ordered? Patient stay healthy
NGS $650 – $2000 in 2018, in 2016 it was $25,000 cost of testing, cost of drugs
show us any value as good value – avoiding patient going to MDs Office, Hospital, ER – cost increase due to Pharmacogenomics testing $5K per test
Guidelines on ordering genomic testing, AI can assist providers, MDs need to catch up on a weekly basis
CMS Guideline: every test ordered must guide treatment otherwise not covered
Scott Ramsey, M.D., Ph.D., Full Member, Fred Hutchinson Cancer Research Center; Director, Hutchinson Institute for Cancer Outcomes Research
Value and utility are interconnected
cost effectiveness of NGS in melanoma: single gene testing – EGFR vs NGS – help clinicians to evaluate Lung Cancer
PRESENTER | Shreeram Aradhye, M.D., Head of Global Medical Affairs, Chief Medical Officer, Pharmaceuticals, Novartis; Board Member, PhRMA Foundation
#1 Prize $50,000 – Dr. Garrison, UK
#2 Prize $25,000 – Dr. Robim Hayeems, Hospital for Sick Children Institute, Toronto, Canada
#3 Prize @ $10,000 – Dr. A Le, PharmD., PhD, Western University of Health Sciences
3:20 p.m.
Networking Break
Light refreshments provided.
3:50 p.m.
Impasse or Inflection Point? — An Investment Analysis
Sustaining the pace of innovation in personalized medicine will require continued investment in new initiatives, but the financial outlook for the field remains unclear. In that context, this panel of investors will examine whether personalized medicine is at an impasse, an inflection point or somewhere in between.
MODERATOR | William A. Sahlman, Ph.D., Baker Foundation Professor, Harvard Business School
market – can it sustain the opportunity – winners and losers
innovative financial models
Biotech IPO, VC, windows slam shut, drug failure – drivers and non
Increasing return to scale: AI, NGS, screening, – foreign money, China
Tsinghua University went back to China from Silicon Valley
Cary Pfeffer, M.D., Partner, Third Rock Ventures
was a decade at Biogen, MS indication drug, no biomarkers for patients – efficacy was in 50% non respondents 25%
Genomic sequencing to identify patient populations – no good effective medicine without target therapy
Mayocardia – drug in CVD for patients identified by Genomics
Genomics information needed to develop drugs
Michael Pellini, M.D., Managing Partner, Section 32; Board Member, Personalized Medicine Coalition
Impasse or Inflection Point? it s Inflection Point NOT an Impasse
Diagnostics component inside 4.8 Trillion in the therapeutics selection in the system as a whole
Foundation Medicine saw Roche as Big brother with International reach
Patients and Consumers will force in five years figuring out – every diagnosis of cancer will be sequenced and the infrastructure to interpret results and paid for
Salveen Richter, C.F.A., Vice President, Research Division, Goldman Sachs
innovative and disruptive, orphan drugs, Health IT, US Market 3 trillion – size of the opportunity 80% genetically driven
Cancer, CART therapy, easier to pay by performance, cost of the drug itself. profit in the 1st generation od Pharma manufacturers
One time pricing vs further indications, annuity type system, Hemophilia – $19Million market,
Europe successful in financing Health care — in the US — system must change – investment will flee, to fund pricing drug is key in changing the system CART Pricing is still difficult to pay for
Sequencing cost plunged, public investors placing funding in start ups even without return in the horizon, companies with multiple modalities spurring innovation – confusing in the investment side, technologies become obsolete very fast
Europe vs US, China is different no regulation like FDA,talent from US Pharma went back to China
4:50 p.m.
Closing Remarks
SPEAKER | Edward Abrahams, Ph.D., President, Personalized Medicine Coalition
PMC President: Times’ Critique of Streamlined Regulatory Approval for Personalized Treatments ‘Ignores Promising Implications’ of Field
WASHINGTON (June 13, 2018) — In response to an editorial published on June 9 by the New York Times titled “Easier Drug Approval, at What Price?,” Personalized Medicine Coalition (PMC) President Edward Abrahams today defends a series of decisions by the U.S. Food and Drug Administration (FDA) over the last several years that have streamlined the regulatory review process for personalized medicines.
“Unlike FDA, which has been an engine for innovation under the direction of Scott Gottlieb and his predecessors, ‘Easier Drug Approval, at What Price?’ ignores the promising implications of reforms in regulatory science that FDA has put in place to facilitate a new appreciation of how different individuals respond to selected treatments,” Abrahams said.
As PMC underlined earlier this year in a report titled Personalized Medicine at FDA: 2017 Progress Report, personalized medicines now account for one of every four drugs the agency approves. The Times’ editorial, which was also published online under the headline “Easier Drug Approval Isn’t Cutting Drug Prices,” contends that “it’s not clear that people, as opposed to drug companies, are feeling much benefit” from the streamlined regulatory review pathways that bring personalized treatments to market faster.
Abrahams disagrees, noting that in non-small cell lung cancer, for example, a disease that was nearly untreatable 20 years ago, there are now multiple drugs on the market that target a patient’s particular tumor. As indicated by the U.S. National Cancer Institute (NCI), these treatments “improve the survival of subsets of patients with metastatic disease.”
Furthermore, because targeted therapies zero in on specific cancerous mutations, doctors can use diagnostic tests to identify with much greater certainty the patients who will likely benefit from them, sparing expenses and side effects for those will not. That logic underpins FDA’s decision to streamline its regulatory processes, to ensure that patients who will benefit from promising targeted therapies — many of whom have few remaining options — can access those treatments without unnecessary delay.
“By putting in place smarter policies to encourage the efficient development of personalized drugs whose safety and efficacy profiles are often higher than one-size-fits-all, trial-and-error treatments, FDA serves the interests not only of patients but also the health system, which spends too much money on ineffective treatments,” Abrahams said.
To evaluate the American public’s interest in personalized medicine, PMC and GenomeWeb recently commissioned Public Perspectives on Personalized Medicine: A Survey of U.S. Public Opinion, which was published in May. Two-thirds of Americans indicated in the survey that they appreciate personalized medicine’s potential, and the majority expressed concerns about whether they will have access to personalized tests and treatments in the future.
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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.
In response to a Wall Street Journal op-ed and request for information about innovative ways to pay for and deliver health care in the U.S., the Personalized Medicine Coalition has encouraged the Centers for Medicare & Medicaid Services (CMS) to spearhead models that empower physicians to move away from the current standard of care when patient outcomes can be improved by tailoring care to a patient’s genetics and other factors:
In keeping with PMC’s mission to underline the significance of personalized medicine to patients and the health system, the Coalition’s comment letter contends that personalized medicine products and services can increase the overall value of dollars spent by improving health outcomes.
CMS’ previous efforts to advance new payment models, the letter notes, were met with resistance largely because they focused on reducing overall health care costs without adequately considering whether those reductions would result in a disproportionate decrease in the outcomes that matter to patients.
PMC indicates in the letter that the guiding principles put forth in CMS’ request for information provide “reasonable assurance” that the agency plans to proceed at “a more measured pace” going forward.
“We believe that personalized medicine has the potential to help CMS deliver on its goal of [affordable, accessible health care] if [the agency] focuses on maximizing individual patient outcomes, if new models are fully evaluated before large-scale implementation, if payment is not rooted in current standard of care, and if physicians have the flexibility to tailor care based on a patient’s genetics and other factors,” the letter reads.
Article ID #155: Geneticist George Church: A Future Without Limits. Published on 10/24/2014
WordCloud Image Produced by Adam Tubman
UPDATED 12/05/2020
In the future, George Church believes, almost everything will be better because of genetics. If you have a medical problem, your doctor will be able to customize a treatment based on your specific DNA pattern. When you fill up your car, you won’t be draining the world’s dwindling supply of crude oil, because the fuel will come from microbes that have been genetically altered to produce biofuel. When you visit the zoo, you’ll be able to take your children to the woolly mammoth or passenger pigeon exhibits, because these animals will no longer be extinct. You’ll be able to do these things, that is, if the future turns out the way Church envisions it—and he’s doing everything he can to see that it does.
UPDATED 12/05/2020
George Church backs a startup solution to the massive gene therapy manufacturing bottleneck
Source: https://endpts.com/george-church-backs-a-startup-solution-to-the-massive-gene-therapy-manufacturing-bottleneck/ Jason Mast: Associate Editor George Church and his graduate students have spent the last decade seeding startups on the razor’s edge between biology and science fiction: gene therapy to prevent aging, CRISPRed pigs that can be used to harvest organs for transplant, and home kits to test your poop for healthy or unhealthy bacteria. (OK, maybe they’re not all on that razor’s edge.)
But now a new spinout from the Department of Genetics’ second floor is tackling a far humbler problem — one that major company after major company has stumbled over as they tried to get cures for rare diseases and other gene therapies into the clinic and past regulators: How the hell do you build these?
CEO Lex Vovner of 64x Bio
“There’s a lot happening for new therapies but not enough attention around this problem,” Lex Rovner, who was a post-doc at Church’s lab from 2015 to 2018, told Endpoints News. “And if we don’t figure out how to fix this, many of these therapies won’t even reach patients.”
This week, with Church and a couple other prominent scientists as co-founders, Rovner launched 64x Bio to tackle one key part of the manufacturing bottleneck. They won’t be looking to retrofit plants or build gene therapy factories, as Big Pharma and big biotech are now spending billions to do. Instead, with $4.5 million in seed cash, they will try to engineer the individual cells that churn out a critical component of the therapies.
George Church The goal is to build cells that are fine-tuned to do nothing but spit out the viral vectors that researchers and drug developers use to shuttle gene therapies into the body. Different vectors have different demands; 64x Bio will look to make efficient cellular factories for each.
“While a few general ways to increase vector production may exist, each unique vector serotype and payload poses a specific challenge,” Church said in an emailed statement. “Our platform enables us to fine tune custom solutions for these distinct combinations that are particularly hard to overcome.”
Before joining Church’s lab, Rovner did her graduate work at Yale, where she studied how to engineer bacteria to produce new kinds of protein for drugs or other purposes. And after leaving Church’s lab in 2018, she initially set out to build a manufacturing startup with a broad focus.
Yet as she spoke with hundreds of biotech executives on LinkedIn and in coffee shops around Cambridge, the same issue kept popping up: They liked their gene therapy technology in the lab but they didn’t know how to scale it up.
“Everyone kept saying the same thing,” Rovner said. “We basically realized there’s this huge problem.”
The issue would soon make headlines in industry publications: bluebird delaying the launch of Zynteglo, Novartis delaying the launch of Zolgensma in the EU, Axovant delaying the start of their Parkinson’s trial.
Part of the problem, Rovner said, is that gene therapies are delivered on viral vectors. You can build these vectors in mammalian cell lines by feeding them a small circular strand of DNA called a plasmid. The problem is that mammalian cells have, over billions of years, evolved tools and defenses precisely to avoid making viruses. (Lest the mammal they live in die of infection).
There are genetic mutations that can turn off some of the internal defenses and unleash a cell’s ability to produce virus, but they’re rare and hard to find. Other platforms, Rovner said, try to find these mutations by using CRISPR to knock out genes in different cells and then screening each of them individually, a process that can require hundreds of thousands of different 100-well plates, with each well containing a different group of mutant cells.
“It’s just not practical, and so these platforms never find the cells,” Rovner said.
64x Bio will try to find them by building a library of millions of mutant mammalian cells and then using a molecular “barcoding” technique to screen those cells in a single pool. The technique, Rovner said, lets them trace how much vector any given cell produces, allowing researchers to quickly identify super-producing cells and their mutations.
The technology was developed partially in-house but draws from IP at Harvard and the Wyss Institute. Harvard’s Pam Silver and Wyss’s Jeffrey Way are co-founders.
The company is now based in SoMa in San Francisco. With the seed cash from Fifty Years, Refactor and First Round Capital, Rovner is recruiting and looking to raise a Series A soon. They’re in talks with pharma and biotech partners, while they try to validate the first preclinical and clinical applications.
Gene therapy is one focus, but Rovner said the platform works for anything that involves viral vector, including vaccines and oncolytic viruses. You just have to find the right mutation.
“It’s the rare cell you’re looking for,” she said.
AUTHOR Jason Mast Associate Editor jason@endpointsnews.com @JasonMMast Jason Mas
In 2005 he launched the Personal Genome Project, with the goal of sequencing and sharing the DNA of 100,000 volunteers. With an open-source database of that size, he believes, researchers everywhere will be able to meaningfully pursue the critical task of correlating genetic patterns with physical traits, illnesses, and exposure to environmental factors to find new cures for diseases and to gain basic insights into what makes each of us the way we are. Church, tagged as subject hu43860C, was first in line for testing. Since then, more than 13,000 people in the U.S., Canada, and the U.K. have volunteered to join him, helping to establish what he playfully calls the Facebook of DNA.
Church has made a career of defying the impossible. Propelled by the dizzying speed of technological advancement since then, the Personal Genome Project is just one of Church’s many attempts to overcome obstacles standing between him and the future.
“It’s not for everyone,” he says. “But I see a trend here. Openness has changed since many of us were young. People didn’t use to talk about sexuality or cancer in polite society. This is the Facebook generation.” If individuals were told which diseases or medical conditions they were genetically predisposed to, they could adjust their behavior accordingly, he reasoned. Although universal testing still isn’t practical today, the cost of sequencing an individual genome has dropped dramatically in recent years, from about $7 million in 2007 to as little as $1,000 today.
“It’s all too easy to dismiss the future,” he says. “People confuse what’s impossible today with what’s impossible tomorrow.”, especially through the emerging discipline of “synthetic” biology. The basic idea behind synthetic biology, he explained, was that natural organisms could be reprogrammed to do things they wouldn’t normally do, things that might be useful to people. In pursuit of this, researchers had learned not only how to read the genetic code of organisms but also how to write new code and insert it into organisms. Besides making plastic, microbes altered in this way had produced carpet fibers, treated wastewater, generated electricity, manufactured jet fuel, created hemoglobin, and fabricated new drugs. But this was only the tip of the iceberg, Church wrote. The same technique could also be used on people.
“Every cell in our body, whether it’s a bacterial cell or a human cell, has a genome,” he says. “You can extract that genome—it’s kind of like a linear tape—and you can read it by a variety of methods. Similarly, like a string of letters that you can read, you can also change it. You can write, you can edit it, and then you can put it back in the cell.”
This April, the Broad Institute, where Church holds a faculty appointment, was awarded a patent for a new method of genome editing called CRISPR (clustered regularly interspersed short palindromic repeats), which Church says is one of the most effective tools ever developed for synthetic biology. By studying the way that certain bacteria defend themselves against viruses, researchers figured out how to precisely cut DNA at any location on the genome and insert new material there to alter its function. Last month, researchers at MIT announced they had used CRISPR to cure mice of a rare liver disease that also afflicts humans. At the same time, researchers at Virginia Tech said they were experimenting on plants with CRISPR to control salt tolerance, improve crop yield, and create resistance to pathogens.
The possibilities for CRISPR technology seem almost limitless, Church says. If researchers have stored a genetic sequence in a computer, they can order a robot to produce a piece of DNA from the data. That piece can then be put into a cell to change the genome. Church believes that CRISPR is so promising that last year he co-founded a genome-editing company, Editas, to develop drugs for currently incurable diseases.
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