Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
Imagine a scenario, where years from now, one of your organs stop working properly. What would you do? The current option is to wait in line for a transplant, hoping that the donor is a match. But what if you can get an organ ready for you with no chance of rejection? Even though it may sound like science fiction at the current moment, organ 3D bioprinting can revolutionize medicine and health care.
I have always found the field of tissue engineering and 3D bioprinting fascinating. What interests me about 3D bioprinting is that it has the capacity to be a game changer, because it would make organs widely available to those who need them and it would eliminate the need for a living or deceased donor. Moreover, it would be beneficial for pediatric patients who suffer specific problems that the current bio-prosthetic options might not address. It would minimize the risk of rejection as well as the components would be customized to size.
There have been advancements in the field of 3D bioprinting and one such advancement is using a 3D printed cranium by neurosurgeons at the University Medical Centre Utrecht. The patient was a young woman who suffered from a chronic bone disorder. The 3D reconstruction of her skull would minimize the brain damage that might have occurred if doctors used a durable plastic cranium.
So, what exactly is bioprinting? 3D bioprinting is an additive manufacturing procedure where biomaterials, such as cells and growth factors, are combined to generate tissue-like structures that duplicate natural tissues. At its core, bioprinting works in a similar way to conventional 3D printing. A digital model becomes a physical 3D object layer-by-layer. However, in the case of bioprinting, a living cell suspension is used instead of a thermoplastic.
The procedure mostly involves preparation, printing, maturation and application and can be summarized in three steps:
Pre-bioprinting step which includes creating a digital model obtained by using computed tomography (CT) and magnetic resonance imaging (MRI) scans which are then fed to the printer.
Bioprinting step where the actual printing process takes place, where the bioink is placed in a printer cartridge and deposition occurs based on the digital model.
Post-bioprinting step is the mechanical and chemical stimulation of printed parts in order to create stable biostructures which can ultimately be implanted.
3D bioprinting allows suitable microarchitectures that provide mechanical stability and promote cell ingrowth to be produced while preventing any homogeneity issues that occur after conventional cell seeding, such as cell placement. Immediate vascularization of implanted scaffolds is critical, because it provides an influx of nutrients and outflow of by-products preventing necrosis. The benefits of homogeneous seeded scaffolds are that it allows them to integrate faster into the host tissue, uniform cell growth in vivo and lower risk of rejection.
However, in order to address the limitations of the commercially available technology for producing tissue implants, researchers are working to develop a 3D bioprinter that can fit into a laminar flow hood, ultra-low cost and customizable for different organs. Bioprinting can be applied in a clinical setting where the ultimate goal is to implant 3D bioprinted structures into the patients, it is necessary to maintain sterile printing solutions and ensure accuracy in complex tissues, needed for cell-to-cell distances and correct output.
The final aim of bioprinting is to promote an alternative to autologous and allogeneic tissue implants, which will replace animal testing for the study of disease and development of treatments. We know that for now a short-term goal for 3D bioprinting is to create alternatives to animal testing and to increase the speed of drug testing. The long-term goal is to change the status quo, to develop a personalized organ made from patient’s own cells. However, some ethical challenges still exist regarding the ownership of the organ.
A powerful starting point is the creation of tissue components for heart, liver, pancreas, and other vital organs. Moreover, each small progress in 3D bioprinting will allow 3D bioprinting to make organs widely available to those who need them, instead of waiting years for a transplant to become available.
Real Time Coverage @BIOConvention #BIO2019: Issues of Risk and Reproduceability in Translational and Academic Collaboration; 2:30-4:00 June 3 Philadelphia PA
Translating academic research into products and new therapies is a very risky venture as only 1% of academic research has been successfully translated into successful products.
Collaboration from Chicago area universities like U of Chicago, Northwestern, etc. First phase was enhance collaboration between universities by funding faculty recruitment and basic research. Access to core facilities across universities. Have expanded to give alternatives to company formation.
Most academic PI are not as savvy to start a biotech so they bring in biotechs and build project teams as well as developing a team of ex pharma and biotech experts. Derisk as running as one asset project. Partner as early as possible. A third of their pipeline have been successfully partnered. Work with investors and patent attorneys.
Focused on getting PIs to get to startup. Focused on oncology and vaccines and I/O. The result can be liscensing or partnership. Running around 50 to 60 projects. Creating a new company from these US PI partnerships.
Most projects from Harvard have been therapeutics-based. At Harvard they have a network of investors ($50 million). They screen PI proposals based on translateability and what investors are interested in.
In Chicago they solicit multiple projects but are agnostic on area but as they are limited they are focused on projects that will assist in developing a stronger proposal to investor/funding mechanism.
NYU goes around university doing due diligence reaching out to investigators. They shop around their projects to wet their investors, pharma appetite future funding. At Takeda they have five centers around US. They want to have more input so go into the university with their scientists and discuss ideas.
Challenges:
Takeda: Data Validation very important. Second there may be disconnect with the amount of equity the PI wants in the new company as well as management. Third PIs not aware of all steps in drug development.
Harvard: Pharma and biotech have robust research and academic does not have the size or scope of pharma. PIs must be more diligent on e.g. the compounds they get from a screen… they only focus narrowly
NYU: bring in consultants as PIs don’t understand all the management issues. Need to understand development so they bring in the experts to help them. Pharma he feels have to much risk aversion and none of their PIs want 100% equity.
Chicago: they like to publish at early stage so publication freedom is a challenge
Dr. Freedman: Most scientists responding to Nature survey said yes a reproduceability crisis. The reasons: experimental bias, lack of validation techniques, reagents, and protocols etc.
And as he says there is a great ECONOMIC IMPACT of preclinical reproducability issues: to the tune of $56 billion of irreproducable results (paper published in PLOS Biology). If can find the core drivers of this issue they can solve the problem. STANDARDS are constantly used in various industries however academic research are lagging in developing such standards. Just the problem of cell line authentication is costing $4 billion.
Dr. Cousins: There are multiple high throughput screening (HTS) academic centers around the world (150 in US). So where does the industry go for best practices in assays? Eli Lilly had developed a manual for HTS best practices and in 1984 made publicly available (Assay Guidance Manual). To date there have been constant updates to this manual to incorporate new assays. Workshops have been developed to train scientists in these best practices.
NIH has been developing new programs to address these reproducability issues. Developed a method called
“Ring Testing Initiative” where multiple centers involved in sharing reagents as well as assays and allowing scientists to test at multiple facilities.
Dr.Tong: Reproduceability of Microarrays: As microarrays were the only methodology to do high through put genomics in the early 2000s, and although much research had been performed to standardize and achieve best reproduceability of the microarray technology (determining best practices in spotting RNA on glass slides, hybridization protocols, image analysis) little had been done on evaluating the reproducibility of results obtained from microarray experiments involving biological samples. The advent of Artificial Intelligence and Machine Learning though can be used to help validate microarray results. This was done in a Nature Biotechnology paper (Nature Biotechnologyvolume28, pages827–838 (2010)) by an international consortium, the International MAQC (Microarray Quality Control) Society and can be found here
However Dr. Tong feels there is much confusion in how we define reproduceability. Dr. Tong identified a few key points of data reproduceability:
Traceability: what are the practices and procedures from going from point A to point B (steps in a protocol or experimental design)
Repeatability: ability to repeat results within the same laboratory
Replicatablilty: ability to repeat results cross laboratory
Transferability: are the results validated across multiple platforms?
The panel then discussed the role of journals and funders to drive reproduceability in research. They felt that editors have been doing as much as they can do as they receive an end product (the paper) but all agreed funders need to do more to promote data validity, especially in requiring that systematic evaluation and validation of each step in protocols are performed.. There could be more training of PIs with respect to protocol and data validation.
Other Articles on Industry/Academic Research Partnerships and Translational Research on this Open Access Online Journal Include
Can Blockchain Technology and Artificial Intelligence Cure What Ails Biomedical Research and Healthcare, 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)
Can Blockchain Technology and Artificial Intelligence Cure What Ails Biomedical Research and Healthcare
Curator: Stephen J. Williams, Ph.D.
Updated 12/18/2018
In the efforts to reduce healthcare costs, provide increased accessibility of service for patients, and drive biomedical innovations, many healthcare and biotechnology professionals have looked to advances in digital technology to determine the utility of IT to drive and extract greater value from healthcare industry. Two areas of recent interest have focused how best to use blockchain and artificial intelligence technologies to drive greater efficiencies in our healthcare and biotechnology industries.
More importantly, with the substantial increase in ‘omic data generated both in research as well as in the clinical setting, it has become imperative to develop ways to securely store and disseminate the massive amounts of ‘omic data to various relevant parties (researchers or clinicians), in an efficient manner yet to protect personal privacy and adhere to international regulations. This is where blockchain technologies may play an important role.
A recent Oncotarget paper by Mamoshina et al. (1) discussed the possibility that next-generation artificial intelligence and blockchain technologies could synergize to accelerate biomedical research and enable patients new tools to control and profit from their personal healthcare data, and assist patients with their healthcare monitoring needs. According to the abstract:
The authors introduce new concepts to appraise and evaluate personal records, including the combination-, time- and relationship value of the data. They also present a roadmap for a blockchain-enabled decentralized personal health data ecosystem to enable novel approaches for drug discovery, biomarker development, and preventative healthcare. In this system, blockchain and deep learning technologies would provide the secure and transparent distribution of personal data in a healthcare marketplace, and would also be useful to resolve challenges faced by the regulators and return control over personal data including medical records to the individual.
The review discusses:
Recent achievements in next-generation artificial intelligence
Basic concepts of highly distributed storage systems (HDSS) as a preferred method for medical data storage
Open source blockchain Exonium and its application for healthcare marketplace
A blockchain-based platform allowing patients to have control of their data and manage access
How advances in deep learning can improve data quality, especially in an era of big data
Advances in Artificial Intelligence
Integrative analysis of the vast amount of health-associated data from a multitude of large scale global projects has proven to be highly problematic (REF 27), as high quality biomedical data is highly complex and of a heterogeneous nature, which necessitates special preprocessing and analysis.
Increased computing processing power and algorithm advances have led to significant advances in machine learning, especially machine learning involving Deep Neural Networks (DNNs), which are able to capture high-level dependencies in healthcare data. Some examples of the uses of DNNs are:
Prediction of drug properties(2, 3) and toxicities(4)
Generative Adversarial Networks (https://arxiv.org/abs/1406.2661): requires good datasets for extensive training but has been used to determine tumor growth inhibition capabilities of various molecules (7)
Recurrent neural Networks (RNN): Originally made for sequence analysis, RNN has proved useful in analyzing text and time-series data, and thus would be very useful for electronic record analysis. Has also been useful in predicting blood glucose levels of Type I diabetic patients using data obtained from continuous glucose monitoring devices (8)
Transfer Learning: focused on translating information learned on one domain or larger dataset to another, smaller domain. Meant to reduce the dependence on large training datasets that RNN, GAN, and DNN require. Biomedical imaging datasets are an example of use of transfer learning.
One and Zero-Shot Learning: retains ability to work with restricted datasets like transfer learning. One shot learning aimed to recognize new data points based on a few examples from the training set while zero-shot learning aims to recognize new object without seeing the examples of those instances within the training set.
Highly Distributed Storage Systems (HDSS)
The explosion in data generation has necessitated the development of better systems for data storage and handling. HDSS systems need to be reliable, accessible, scalable, and affordable. This involves storing data in different nodes and the data stored in these nodes are replicated which makes access rapid. However data consistency and affordability are big challenges.
Blockchain is a distributed database used to maintain a growing list of records, in which records are divided into blocks, locked together by a crytosecurity algorithm(s) to maintain consistency of data. Each record in the block contains a timestamp and a link to the previous block in the chain. Blockchain is a distributed ledger of blocks meaning it is owned and shared and accessible to everyone. This allows a verifiable, secure, and consistent history of a record of events.
Data Privacy and Regulatory Issues
The establishment of the Health Insurance Portability and Accountability Act (HIPAA) in 1996 has provided much needed regulatory guidance and framework for clinicians and all concerned parties within the healthcare and health data chain. The HIPAA act has already provided much needed guidance for the latest technologies impacting healthcare, most notably the use of social media and mobile communications (discussed in this article Can Mobile Health Apps Improve Oral-Chemotherapy Adherence? The Benefit of Gamification.). The advent of blockchain technology in healthcare offers its own unique challenges however HIPAA offers a basis for developing a regulatory framework in this regard. The special standards regarding electronic data transfer are explained in HIPAA’s Privacy Rule, which regulates how certain entities (covered entities) use and disclose individual identifiable health information (Protected Health Information PHI), and protects the transfer of such information over any medium or electronic data format. However, some of the benefits of blockchain which may revolutionize the healthcare system may be in direct contradiction with HIPAA rules as outlined below:
Issues of Privacy Specific In Use of Blockchain to Distribute Health Data
Blockchain was designed as a distributed database, maintained by multiple independent parties, and decentralized
Linkage timestamping; although useful in time dependent data, proof that third parties have not been in the process would have to be established including accountability measures
Blockchain uses a consensus algorithm even though end users may have their own privacy key
Applied cryptography measures and routines are used to decentralize authentication (publicly available)
Blockchain users are divided into three main categories: 1) maintainers of blockchain infrastructure, 2) external auditors who store a replica of the blockchain 3) end users or clients and may have access to a relatively small portion of a blockchain but their software may use cryptographic proofs to verify authenticity of data.
YouTube video on How #Blockchain Will Transform Healthcare in 25 Years (please click below)
In Big Data for Better Outcomes, BigData@Heart, DO->IT, EHDN, the EU data Consortia, and yes, even concepts like pay for performance, Richard Bergström has had a hand in their creation. The former Director General of EFPIA, and now the head of health both at SICPA and their joint venture blockchain company Guardtime, Richard is always ahead of the curve. In fact, he’s usually the one who makes the curve in the first place.
Please click on the following link for a podcast on Big Data, Blockchain and Pharma/Healthcare by Richard Bergström:
References
Mamoshina, P., Ojomoko, L., Yanovich, Y., Ostrovski, A., Botezatu, A., Prikhodko, P., Izumchenko, E., Aliper, A., Romantsov, K., Zhebrak, A., Ogu, I. O., and Zhavoronkov, A. (2018) Converging blockchain and next-generation artificial intelligence technologies to decentralize and accelerate biomedical research and healthcare, Oncotarget9, 5665-5690.
Aliper, A., Plis, S., Artemov, A., Ulloa, A., Mamoshina, P., and Zhavoronkov, A. (2016) Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data, Molecular pharmaceutics13, 2524-2530.
Wen, M., Zhang, Z., Niu, S., Sha, H., Yang, R., Yun, Y., and Lu, H. (2017) Deep-Learning-Based Drug-Target Interaction Prediction, Journal of proteome research16, 1401-1409.
Gao, M., Igata, H., Takeuchi, A., Sato, K., and Ikegaya, Y. (2017) Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds, Journal of pharmacological sciences133, 70-78.
Putin, E., Mamoshina, P., Aliper, A., Korzinkin, M., Moskalev, A., Kolosov, A., Ostrovskiy, A., Cantor, C., Vijg, J., and Zhavoronkov, A. (2016) Deep biomarkers of human aging: Application of deep neural networks to biomarker development, Aging8, 1021-1033.
Vandenberghe, M. E., Scott, M. L., Scorer, P. W., Soderberg, M., Balcerzak, D., and Barker, C. (2017) Relevance of deep learning to facilitate the diagnosis of HER2 status in breast cancer, Scientific reports7, 45938.
Kadurin, A., Nikolenko, S., Khrabrov, K., Aliper, A., and Zhavoronkov, A. (2017) druGAN: An Advanced Generative Adversarial Autoencoder Model for de Novo Generation of New Molecules with Desired Molecular Properties in Silico, Molecular pharmaceutics14, 3098-3104.
Ordonez, F. J., and Roggen, D. (2016) Deep Convolutional and LSTM Recurrent Neural Networks for Multimodal Wearable Activity Recognition, Sensors (Basel)16.
December 5, 2018 | The boom of blockchain and distributed ledger technologies have inspired healthcare organizations to test the capabilities of their data. Quest Diagnostics, in partnership with Humana, MultiPlan, and UnitedHealth Group’s Optum and UnitedHealthcare, have launched a pilot program that applies blockchain technology to improve data quality and reduce administrative costs associated with changes to healthcare provider demographic data.
The collective body, called Synaptic Health Alliance, explores how blockchain can keep only the most current healthcare provider information available in health plan provider directories. The alliance plans to share their progress in the first half of 2019.
Providing consumers looking for care with accurate information when they need it is essential to a high-functioning overall healthcare system, Jason O’Meara, Senior Director of Architecture at Quest Diagnostics, told Clinical Informatics News in an email interview.
“We were intentional about calling ourselves an alliance as it speaks to the shared interest in improving health care through better, collaborative use of an innovative technology,” O’Meara wrote. “Our large collective dataset and national footprints enable us to prove the value of data sharing across company lines, which has been limited in healthcare to date.”
O’Meara said Quest Diagnostics has been investing time and resources the past year or two in understanding blockchain, its ability to drive purpose within the healthcare industry, and how to leverage it for business value.
“Many health care and life science organizations have cast an eye toward blockchain’s potential to inform their digital strategies,” O’Meara said. “We recognize it takes time to learn how to leverage a new technology. We started exploring the technology in early 2017, but we quickly recognized the technology’s value is in its application to business to business use cases: to help transparently share information, automate mutually-beneficial processes and audit interactions.”
Quest began discussing the potential for an alliance with the four other companies a year ago, O’Meara said. Each company shared traits that would allow them to prove the value of data sharing across company lines.
“While we have different perspectives, each member has deep expertise in healthcare technology, a collaborative culture, and desire to continuously improve the patient/customer experience,” said O’Meara. “We also recognize the value of technology in driving efficiencies and quality.”
Following its initial launch in April, Synaptic Health Alliance is deploying a multi-company, multi-site, permissioned blockchain. According to a whitepaper published by Synaptic Health, the choice to use a permissioned blockchain rather than an anonymous one is crucial to the alliance’s success.
“This is a more effective approach, consistent with enterprise blockchains,” an alliance representative wrote. “Each Alliance member has the flexibility to deploy its nodes based on its enterprise requirements. Some members have elected to deploy their nodes within their own data centers, while others are using secured public cloud services such as AWS and Azure. This level of flexibility is key to growing the Alliance blockchain network.”
As the pilot moves forward, O’Meara says the Alliance plans to open ability to other organizations. Earlier this week Aetna and Ascension announced they joined the project.
“I am personally excited by the amount of cross-company collaboration facilitated by this project,” O’Meara says. “We have already learned so much from each other and are using that knowledge to really move the needle on improving healthcare.”
November 29, 2018 | The US Department of Health and Human Services (HHS) is making waves in the blockchain space. The agency’s Division of Acquisition (DA) has developed a new system, called Accelerate, which gives acquisition teams detailed information on pricing, terms, and conditions across HHS in real-time. The department’s Associate Deputy Assistant Secretary for Acquisition, Jose Arrieta, gave a presentation and live demo of the blockchain-enabled system at the Distributed: Health event earlier this month in Nashville, Tennessee.
Accelerate is still in the prototype phase, Arrieta said, with hopes that the new system will be deployed at the end of the fiscal year.
HHS spends around $25 billion a year in contracts, Arrieta said. That’s 100,000 contracts a year with over one million pages of unstructured data managed through 45 different systems. Arrieta and his team wanted to modernize the system.
“But if you’re going to change the way a workforce of 20,000 people do business, you have to think your way through how you’re going to do that,” said Arrieta. “We didn’t disrupt the existing systems: we cannibalized them.”
The cannibalization process resulted in Accelerate. According to Arrieta, the system functions by creating a record of data rather than storing it, leveraging machine learning, artificial intelligence (AI), and robotic process automation (RPA), all through blockchain data.
“We’re using that data record as a mechanism to redesign the way we deliver services through micro-services strategies,” Arrieta said. “Why is that important? Because if you have a single application or data use that interfaces with 55 other applications in your business network, it becomes very expensive to make changes to one of the 55 applications.”
Accelerate distributes the data to the workforce, making it available to them one business process at a time.
“We’re building those business processes without disrupting the existing systems,” said Arrieta, and that’s key. “We’re not shutting off those systems. We’re using human-centered design sessions to rebuild value exchange off of that data.”
The first application for the system, Arrieta said, can be compared to department stores price-matching their online competitors.
It takes the HHS close to a month to collect the amalgamation of data from existing system, whether that be terms and conditions that drive certain price points, or software licenses.
“The micro-service we built actually analyzes that data, and provides that information to you within one second,” said Arrieta. “This is distributed to the workforce, to the 5,000 people that do the contracting, to the 15,000 people that actually run the programs at [HHS].”
This simple micro-service is replicated on every node related to HHS’s internal workforce. If somebody wants to change the algorithm to fit their needs, they can do that in a distributed manner.
Arrieta hopes to use Accelerate to save researchers money at the point of purchase. The program uses blockchain to simplify the process of acquisition.
“How many of you work with the federal government?” Arrieta asked the audience. “Do you get sick of reentering the same information over and over again? Every single business opportunity you apply for, you have to resubmit your financial information. You constantly have to check for validation and verification, constantly have to resubmit capabilities.”
Wouldn’t it be better to have historical notes available for each transaction? said Arrieta. This would allow clinical researchers to be able to focus on “the things they’re really good at,” instead of red tape.
“If we had the top cancer researcher in the world, would you really want her spending her time learning about federal regulations as to how to spend money, or do you want her trying to solve cancer?” Arrieta said. “What we’re doing is providing that data to the individual in a distributed manner so they can read the information of historical purchases that support activity, and they can focus on the objectives and risks they see as it relates to their programming and their objectives.”
Blockchain also creates transparency among researchers, Arrieta said, which says creates an “uncomfortable reality” in the fact that they have to make a decision regarding data, fundamentally changing value exchange.
“The beauty of our business model is internal investment,” Arrieta said. For instance, the HHS could take all the sepsis data that exists in their system, put it into a distributed ledger, and share it with an external source.
“Maybe that could fuel partnership,” Arrieta said. “I can make data available to researchers in the field in real-time so they can actually test their hypothesis, test their intuition, and test their imagination as it relates to solving real-world problems.”
Blockchain-based genomic data hub platform Shivom recently reached its $35 million hard cap within 15 seconds of opening its main token sale. Shivom received funding from a number of crypto VC funds, including Collinstar, Lateral, and Ironside.
The goal is to create the world’s largest store of genomic data while offering an open web marketplace for patients, data donors, and providers — such as pharmaceutical companies, research organizations, governments, patient-support groups, and insurance companies.
“Disrupting the whole of the health care system as we know it has to be the most exciting use of such large DNA datasets,” Shivom CEO Henry Ines told me. “We’ll be able to stratify patients for better clinical trials, which will help to advance research in precision medicine. This means we will have the ability to make a specific drug for a specific patient based on their DNA markers. And what with the cost of DNA sequencing getting cheaper by the minute, we’ll also be able to sequence individuals sooner, so young children or even newborn babies could be sequenced from birth and treated right away.”
While there are many solutions examining DNA data to explain heritage, intellectual capabilities, health, and fitness, the potential of genomic data has largely yet to be unlocked. A few companies hold the monopoly on genomic data and make sizeable profits from selling it to third parties, usually without sharing the earnings with the data donor. Donors are also not informed if and when their information is shared, nor do they have any guarantee that their data is secure from hackers.
Shivom wants to change that by creating a decentralized platform that will break these monopolies, democratizing the processes of sharing and utilizing the data.
“Overall, large DNA datasets will have the potential to aid in the understanding, prevention, diagnosis, and treatment of every disease known to mankind, and could create a future where no diseases exist, or those that do can be cured very easily and quickly,” Ines said. “Imagine that, a world where people do not get sick or are already aware of what future diseases they could fall prey to and so can easily prevent them.”
Shivom’s use of blockchain technology and smart contracts ensures that all genomic data shared on the platform will remain anonymous and secure, while its OmiX token incentivizes users to share their data for monetary gain.
Blockchain will secure the DNA database for 50 million citizens in the eighth-largest state in India. The government of Andhra Pradesh signed a Memorandum of Understanding with a German genomics and precision medicine start-up, Shivom, which announced to start the pilot project soon. The move falls in line with a trend for governments turning to population genomics, and at the same time securing the sensitive data through blockchain.
Andhra Pradesh, DNA, and blockchain
Storing sensitive genetic information safely and securely is a big challenge. Shivom builds a genomic data-hub powered by blockchain technology. It aims to connect researchers with DNA data donors thus facilitating medical research and the healthcare industry.
With regards to Andhra Pradesh, the start-up will first launch a trial to determine the viability of their technology for moving from a proactive to a preventive approach in medicine, and towards precision health. “Our partnership with Shivom explores the possibilities of providing an efficient way of diagnostic services to patients of Andhra Pradesh by maintaining the privacy of the individual data through blockchain technologies,” said J A Chowdary, IT Advisor to Chief Minister, Government of Andhra Pradesh.
Other Articles in this Open Access Journal on Digital Health include:
10:00-10:45 AM The Davids vs. the Cancer Goliath Part 1
Startups from diagnostics, biopharma, medtech, digital health and emerging tech will have 8 minutes to articulate their visions on how they aim to tame the beast.
10,000 cancer patients a month helping patients navigate cancer care with Belong App
Belong Eco system includes all their practitioners and using a trigger based content delivery (posts, articles etc)
most important taking unstructured health data (images, social activity, patient compilance) and converting to structured data
Care+Wear
personally design picc line cover for oncology patients
partners include NBA Major league baseball, Oscar de la Renta,
designs easy access pic line gowns and shirts
OncoPower :Digital Health in a Blockchain Ecosystem
problems associated with patient adherence and developed a product to address this
OncoPower Blockchain: HIPAA compliant using the coin Oncopower security token to incentiavize patients and oncologists to consult with each other or oncologists with tumor boards; this is not an initial coin offering
PolyArum
spinout from UPENN; developing a nanoparticle based radiation therapy; glioblastoma muse model showed great response with gold based nanoparticle and radiation
they see enhanced tumor penetration, and retention of the gold nanoparticles
however most nanoparticles need to be a large size greater than 5 nm to see effect so they used a polymer based particle; see good uptake but excretion past a week so need to re-dose with Au nanoparticles
they are looking for capital and expect to start trials in 2020
Seeker Health
tying to improve the efficiency of clinical trial enrollment
using social networks to find the patients to enroll in clinical trials
steps they use 1) find patients on Facebook, Google, Twitter 2) engage patient screen 3) screening at clinical sites
Seeker Portal is a patient management system: patients referred to a clinical site now can be tracked
11:00- 11:45 AM Breakout: How to Scale Precision Medicine
The potential for precision medicine is real, but is limited by access to patient datasets. How are government entities, hospitals and startups bringing the promise of precision medicine to the masses of oncology patients
Ingo: data is not ordered, only half of patients are tracked in some database, reimbursement a challenge
Eugean: identifying mutations as patients getting more comprehensive genomic coverage, clinical trials are expanding more rapidly as seen in 2018 ASCO
Ingo: general principals related to health outcomes or policy or reimbursement.. human studies are paramount but payers may not allowing for general principals (i.e. an Alk mutation in lung cancer and crizotanib treatment may be covered but maybe not for glioblastoma or another cancer containing similar ALK mutation; payers still depend on clinical trial results)
Andrew: using gene panels and NGS but only want to look for actionable targets; they establish an expert panel which reviews these NGS sequence results to determine actionable mutations
Ankur: they have molecular tumor boards but still if want to prescribe off label and can’t find a clinical trial there is no reimbursement
Andrew: going beyond actionable mutations, although many are doing WES (whole exome sequencing) can we use machine learning to see if there are actionable data from a WES
Ingo: we forget in datasets is that patients have needs today and we need those payment systems and structures today
Eugean: problem is the start from cost (where the cost starts at and was it truly medically necessary)
Norden: there are not enough data sharing to make a decision; an enormous amount of effort to get businesses and technical limitations in data sharing; possibly there are policies needed to be put in place to assimilate datasets and promote collaborations
Ingo: need to take out the middle men between sequencing of patient tumor and treatment decision; middle men are taking out value out of the ‘supply chain’;
Andrew: PATIENTS DON’T OWN their DATA but MOST clinicians agree THEY SHOULD
Ankur: patients are willing to share data but the HIPAA compliance is a barrier
11:50- 12:30 AM Fireside Chat with Michael Pellini, M.D.
Building a Precision Medicine Business from the Ground Up: An Operating and Venture Perspective
Dr. Pellini has spent more than 20 years working on the operating side of four companies, each of which has pushed the boundaries of the standard of care. He will describe his most recent experience at Foundation Medicine, at the forefront of precision medicine, and how that experience can be leveraged on the venture side, where he now evaluates new healthcare technologies.
Roche just bought Foundation Medicine for $2.5 billion. They negotiated over 7 months but aside from critics they felt it was a great deal because it gives them, as a diagnostic venture, the international reach and biotech expertise. Foundation Medicine offered Roche expertise on the diagnostic space including ability to navigate payers and regulatory aspects of the diagnostic business. He feels it benefits all aspects of patient care and the work they do with other companies.
Moderatore: Roche is doing multiple deals to ‘own’ a disease state.
Dr. Pellini: Roche is closing a deal with Flatiron just like how Merck closed deals with genomics companies. He feels best to build the best company on a stand alone basis and provide for patients, then good things will happen. However the problem of achieving scale for Precision Medicine is reimbursement by payers. They still have to keep collecting data and evolving services to suit pharma. They didn’t know if there model would work but when he met with FDA in 2011 they worked with Precision Medicine, said collect the data and we will keep working with you,
However the payers aren’t contributing to the effort. They need to assist some of the young companies that can’t raise the billion dollars needed for all the evidence that payers require. Precision Medicine still have problems, even though they have collected tremendous amounts of data and raised significant money. From the private payer perspective there is no clear roadmap for success.
They recognized that the payers would be difficult but they had a plan but won’t invest in companies that don’t have a plan for getting reimbursement from payers.
Moderator: What is section 32?
Pellini: Their investment arm invests in the spectrum of precision healtcare companies including tech companies. They started with a digital path imaging system that went from looking through a scope and now looking at a monitor with software integrated with medical records. Section 32 has $130 million under management and may go to $400 Million but they want to stay small.
Pellini: we get 4-5 AI pitches a week.
Moderator: Are you interested in companion diagnostics?
Pellini: There may be 24 expected 2018 drug approvals and 35% of them have a companion diagnostic (CDX) with them. however going out ten years 70% may have a CDX associated with them. Payers need to work with companies to figure out how to pay with these CDXs.
Ultra-Pure Melatonin Product Helps Maintain Sleep for Up to 7 Hours
Curator: Gail S. Thornton, M.A.
Co-Editor: The VOICES of Patients, Hospital CEOs, HealthCare Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures
Clinical data from a new pharmacokinetic study suggests that REMfresh®, the first and only continuous release and absorption melatonin (CRA-melatonin), helps maintain sleep for up to 7 hours. REMfresh® contains 99 percent ultra-pure melatonin and is sourced in Western Europe, a factor that is significant and important to many sleep specialists.
Three research abstracts on the REMfresh® data were published in an online supplement in the journal, Sleep, and were presented recently at the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS).
Image SOURCE: Photograph courtesy of Physician’s Seal®.
How REMfresh® Works
REMfresh® (CRA-melatonin) mimics the body’s own 7-hour Mesa Wave™, a natural pattern of melatonin blood levels during a normal night’s sleep cycle.
The study demonstrated the continuous release and absorption of 99 percent ultra-pure melatonin in REMfresh® (CRA-melatonin) was designed to induce sleep onset and provide continuous, lasting restorative sleep over 7 hours.
The scientifically advanced, patented formulation, called Ion Powered Pump (IPP™) technology, replicates the way in which the body naturally releases and absorbs melatonin, unlike conventional melatonin sleep products.
Since REMfresh® (CRA-melatonin) is not a drug, there is no drug hangover.
Image SOURCE: Diagram courtesy of Physician’s Seal®.
Data Based on Scientifically Advanced Delivery Technology
According to the primary study author, David C. Brodner, M.D., “These study results represent an unparalleled breakthrough in drug-free, sleep maintenance that physicians and patients have been waiting for in a sleep product.” Dr. Brodner is a sleep specialist who is double board-certified in Otolaryngology – Head and Neck Surgery and Sleep Medicine and is the founder and principle physician at the Center for Sinus, Allergy, and Sleep Wellness in Palm Beach County, Florida.
Dr. Brodner said, “Melatonin products have been used primarily as a chronobiotic to address sleep disorders, such as jet lag and shift work. The patented delivery system in REMfresh mimics the body’s own natural sleep pattern, so individuals may experience consistent, restorative sleep and have an improved quality of life with this drug-free product.”
Study Findings With REMAKT™
The study findings are based on REMAKT™ (REMAbsorption Kinetics Trial), a U.S.-based randomized, crossover pharmacokinetic (PK) evaluation study in healthy, non-smoking adults that compared REMfresh® (CRA-melatonin) with a market-leading, immediate-release melatonin (IR-melatonin).
The study found that melatonin levels with REMfresh® exceeded the targeted sleep maintenance threshold for a median of 6.7 hours, compared with 3.7 hours with the leading IR-melatonin. Conversely, the levels of the market-leading IR-melatonin formulation dramatically increased 23 times greater than the targeted levels of exogenous melatonin for sleep maintenance and had a rapid decline in serum levels that did not allow melatonin levels to be maintained beyond 4 hours.
Additional analysis presented showed that REMfresh® (CRA-melatonin) builds upon the body of evidence from prolonged-release melatonin (PR-M), which demonstrated in well-conducted, placebo-controlled studies, statistically significant improvement in sleep quality, morning alertness, sleep latency and quality of life in patients aged 55 years and older compared with placebo.
REMfresh® (CRA-melatonin) was designed to overcome the challenges of absorption in the intestines, thereby extending the continual and gradual release pattern of melatonin through the night (known as the Mesa Wave™, a flat-topped hill with steep sides). There was a faster time to Cmax, which is anticipated to result in improved sleep onset, while the extended median plateau time to 6.7 hours and rapid fall-off in plasma levels at the end of the Mesa Wave™ may help to improve sleep maintenance and morning alertness.
Other related articles published in this Open Access Online Scientific Journal include the following:
2017
Sleep Research Society announces 2017 award recipients including Thomas S. Kilduff, PhD, Director, Center for Neuroscience at SRI International in Menlo Park, California
The ubiquitin system produces a protein that greatly restricts the development of cancerous tumors.
A new study by researchers at the Technion-Israel Institute of Technology could hold one key to control cancer cell growth and development. In a paper published in the April 9, 2015 edition of CELL, the team reports on the discovery of two cancer-suppressing proteins.
Distinguished Professor Aaron Ciechanover. Photographer: Dan Porges
The research was conducted in the laboratory of Distinguished Professor Aaron Ciechanover, of the Technion Rappaport Faculty of Medicine. The team was led by research associate Dr. Yelena Kravtsova-Ivantsiv and , included additional research students and colleagues, as well as physicians from the Rambam, Carmel and Hadassah Medical Centers, who are studying tumors and their treatment.
The heretofore-undiscovered proteins were found during ongoing research on the ubiquitin system, an important and vital pathway in the life of the cell, which is responsible for the degradation of defective proteins that could damage the cell if not removed. The ubiquitin system tags these proteins and sends them for destruction in the cellular complex known as the proteasome. The system also removes functional and healthy proteins that are not needed anymore, thereby regulating the processes that these proteins control.
Usually, the proteins that reach the proteasome are completely broken down, but there are some exceptions, and the current line of research examined p105, a long precursor of a key regulator in the cell called NF-κB. It turns out that p105 can be broken down completely in certain cases following its tagging by ubiquitin, but in other cases it is only cut and shortened and becomes a protein called p50.
NF-κB has been identified as a link between inflammation and cancer. The hypothesis of the connection between inflammatory processes and cancer was first suggested in 1863 by German pathologist Rudolph Virchow, and has been confirmed over the years in a long series of studies. Ever since the discovery (nearly 30 years ago) of NF-κB, numerous articles have been published linking it to malignant transformation. It is involved in tumors of various organs (prostate, breast, lung, head and neck, large intestine, brain, etc.) in several parallel ways, including: inhibition of apoptosis (programmed cell death) normally eliminates transformed cells; acceleration of uncontrolled division of cancer cells; formation of new blood vessels (angiogenesis), which are vital to tumor growth; and increased resistance of cancerous cells to irradiation and chemotherapy.
The dramatic effect of these proteins on cancer growth: above the two tumors in the foreground (the control group) are tumors that express high levels of the proteins
As noted, the precursor p105 is “handled” by the ubiquitin system in one of two parallel and equally prevalent ways. It is either destroyed completely, or shortened and transformed to p50. The current research deciphers the decision-making mechanism that determines which process will be applied to the protein: when a ubiquitin system component called KPC1 is involved in the process and attaches ubiquitin to p105, the protein is shortened to become p50. When ubiquitination is mediated by another component of the system (and without KPC1), p105 is degraded.
The ubiquitin molecule within all living cells
The decision between these two options has significant implications on the cell, as the presence of high levels of KPC1 (which generates p50) and p50 (the product of the process) – with the accompanying disruption of the normal ratios between the processes – suppresses the malignant growth and apparently protects the healthy tissue. The current research was conducted on models of human tumors grown in mice, as well as on samples of human tumors, and a strong connection was discovered between the suppression of malignancy and the level of the two proteins, clearly indicating that the increased presence of KPC1 and/or p50 in the tissue can protect it from cancerous tumors.
Professor Ciechanover, who is also the president of the Israel Cancer Society, notes that many more years are required “to establish the research and gain a solid understanding of the mechanisms behind the suppression of the tumors. The development of a drug based on this discovery is a possibility, although not a certainty, and the road to such a drug is long and far from simple.”
Professor Ciechanover won the Nobel Prize in Chemistry in 2004 (jointly with Professors Avram Hershko – also from the Technion – and Irwin Rose, of the Fox Chase Cancer Center) for the discovery of the ubiquitin system. The current line of research is a continuation of that discovery.
President Reuven Rivlin and Indian Prime Minister Narendra Modi, March 29, 2015 (photo credit: Courtesty Tomer Reichmann)
President Reuven Rivlin and Indian Prime Minister Narendra Modi, March 29, 2015 (photo credit: Courtesty Tomer Reichmann)
Days after the Technion announced that a team led by Nobel Prize laureate Professor Aaron Ciechanover had discovered how proteins could be used to suppress cancer and control tumor growth and development, the institute revealed that it had entered into an exclusive agreement with India’s Sun Pharmaceuticals — the world’s fifth-largest specialty generic pharmaceutical company and India’s top pharmaceutical company.
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Under the agreement, researchers from the Technion and Sun will conduct studies on how high concentrations of two proteins can protect tissue from tumors. A study published in the medical journal Cell this week discussed how the proteins can suppress malignancies.
Along with Ciechanover, the research team included Dr. Gila Maor and Professor Ofer Binah. In a statement, Ciechanover said that the research held a great deal of promise of an effective drug for treating cancer, “although this is not a certainty, and the road to such a drug is long and far from simple.”
The deal with Sun is just one of several R&D ventures between Israel and India, on both the business and government levels. So far, the two countries have signed seven bilateral economic and R&D agreements, including one that fosters joint projects on space travel and satellite development.
The joint program aims at attracting additional, world-class support from institutions and individuals who are dedicated to eradicating cancer through focused and efficient research.
Two of the world’s preeminent academic and research institutions — New York University’s Langone Medical Center and Haifa’sTechnion-Israel Institute of Technology — have made a “groundbreaking step forward to advance global collaboration in the fight against cancer formally.
On Wednesday night, they announced a $9 million gift from philanthropists Laura and Isaac Perlmutter that will fund two major, joint research endeavors with potentially far-reaching impact in advancing cancer research. The joint program aims at attracting additional, world-class support from institutions and individuals who are dedicated to eradicating cancer through focused and efficient research, they said in a joint statement.
The first $3 million of the grant will finance six cancer-focused research projects to be conducted by teams spearheaded by co-investigators from both NYU and the Technion. The remaining $6 million will be used to establish a state-of-the-art research facility on Technion’s campus that will support these and other research projects and focus mainly on the emerging field of cancer metabolomics.
“NYU Langone and the Technion have a shared, longstanding commitment to advancing cancer research,” said Dr. Dafna Bar-Sagi, senior vice president and vice dean for science at the New York hospital, chief science officer at NYU School of Medicine and a principal architect of the NYU Langone-Technion partnership. “We are now at a great moment in our institutions’ illustrious histories, a point from which we can jointly leverage the talent and creativity of our researchers toward accelerating breakthroughs. The foresight and the generosity of the Perlmutters, particularly at this time of financial challenge in funding for basic research, will have tremendous impact.”
“Bringing together the unique expertise of researchers from both NYU and the Technion will hopefully enable us to overcome some of the most difficult challenges in treating cancer patients,” said Technion Prof. Aaron Ciechanover, the 2004 Nobel Prize Laureate in Chemistry and Distinguished Research Professor and head of the David and Janet Polak Cancer and Vascular Biology Research Center at the Technion Faculty of Medicine.
Renowned cancer biologist Dr. Benjamin Neel, an expert in the field of cell signal transduction, recently joined the Langone faculty as director of the Perlmutter Cancer Center, and Dr. Eyal Gottlieb, a world leader in cancer metabolism, has been recruited to lead the new research facility at the Technion funded by the Perlmutter gift. Neel will work closely with Ciechanover to lead the collaborative cancer research effort between the two institutions, they said.
In addition, Neel will oversee at NYU the building of world-class translational programs in immunotherapy, cancer genetics/targeted therapies and epigenetics, imaging, as well as expanded programs in clinical care, community outreach and supportive oncology.
The innovative method, developed at the Technion, identifies persons at risk for developing stomach cancer and for detecting tumors at an earlier stage. The prestigious journal Gut, which published the research, notes that the detection method is quick, simple, inexpensive and non-invasive.
Innovative gastric cancer-detection technology
Innovative gastric cancer-detection technology developed by the Technion can be used for the early detection of stomach cancer and for identifying persons at risk for developing the disease. The new detection method, based on breath analysis, has significant advantages over the existing detection technology: Gut reports that the new method is quick, simple, inexpensive and non-invasive.
Gastric cancer is one of the most lethal forms of cancer and in most cases, its diagnosis involves an endoscopy (the insertion of a tube into the esophagus, requiring that the patient fast and receive an intravenous sedative). Treatment is aggressive chemotherapy, radiation and the full or partial removal of the stomach. The disease develops in a series of well-defined steps, but there’s currently no effective, reliable, and non-invasive screening test for picking up these changes early on. Thus, many people succumb to stomach cancer only because it was not diagnosed in time.
The new technology, developed by Prof. Hossam Haick of the Wolfson Faculty of Chemical Engineering, can be used to detect premalignant lesions at the earliest stage, when healthy cells start becoming cancerous.
The research, published in Gut as part of the doctoral thesis of Mr. Haitham Amal, was conducted in conjunction with a Latvian research group headed by Prof. Marcis Leja, based on the largest population sample ever in a trial of this type. 484 people participated in the trial, 99 of whom had already been diagnosed with stomach cancer. All the participants were tested for Helicobacter pylori, a bacterium known to increase the risk for stomach cancer, and two breath samples were taken from each person.
The first sample from each participant was analyzed using the GCMS technique, which measures volatile organic substances in exhaled breath. The researchers noted that GCMS technology cannot be used to detect stomach cancer because the testing is very expensive and requires lengthy processing times and considerable expertise to operate the equipment.
The second breath sample was tested using nanoarray analysis, the unique technology developed by Prof. Haick, combined with a pattern recognition algorithm.
The findings:
Based on the concentrations of 8 specific substances (out of 130) in the oral cavity, the new technology can distinguish between three groups: gastric cancer patients, persons who have precancerous stomach lesions, and healthy individuals.
The new technology accurately distinguishes between the various pre-malignant stages.
The new technology can be used to identify persons at risk for developing gastric cancer.
The diagnosis is accurate, regardless of other factors such as age, sex, smoking habits, alcohol consumption and the use of anti-oxidant drugs.
In short, the nano-array analysis method developed by Prof. Haick is accurate, sensitive technology that provides a simple and inexpensive alternative to existing tests (such as GCMS). This new technology offers early, effective detection of persons at risk for developing stomach cancer, without unnecessary invasive tests (endoscopy). In order to assess the accuracy and effectiveness of the new, a wide-scale clinical trial is currently under way in Europe, with thousands of participants who have cancerous or pre-cancerous tumors.
About Prof. Hossam Haick
Prof. Hossam Haick, who joined the senior staff at the Technion Wolfson Faculty of Chemical Engineering in 2006, has been working since that year on the development of innovative, non-invasive technology for detecting cancer and other diseases. This technology is based on an “electronic nose” – an apparatus capable of detecting illnesses by analyzing a patient’s exhaled breath.
Prof. Haick, a native of Nazareth, completed his Ph.D. studies at the Technion by the time he was 27 and went to the Weizmann Institute of Science in Rehovot and Caltech Institute of Technology in California. He returned to the Technion in 2006 and his research group was awarded one million euros in grants by the European Union, which was very impressed by his research into artificial olfactory systems. Today he heads a consortium that includes Siemens and several universities, research institutes and companies in Germany, Austria, Finland, Ireland, Latvia and Israel. Since joining the senior faculty in the Chemical Engineering Department in 2006, Prof. Haick has won dozens of awards, grants and international honors. These include the Marie Curie Excellence Grant, European Research Council (ERC) grant and the Bill & Melinda Gates Award. Prof. Haick was nominated to MIT’s list of the 35 leading young scientists worldwide, received the Knight of the Order of Academic Palms, from the French Government and won the Hershel Rich Technion Innovation Award (twice), as well as the Tenne Prize for Excellence in the Science of Nanotechnology. He has also been recognized for his outstanding teaching skills and is the recipient of the Yanai Prize for Academic Excellence. In 2014, at the initiative of the president of the Technion, Prof. Haick headed an MOOC (Massive Open Online Course) in nanotechnology and nano-sensors that had an enrollment of 42,000.
This month is Breast Cancer Awareness Month in Israel and around the world. Innovative technology developed at the Technion Faculty of Biomedical Engineering will enable the prediction of cancer metastasis after the appearance of breast cancer. The technology, whose efficacy has been proven in preliminary laboratory-trials, is entering into advanced testing using cells from patients undergoing surgery.
In contrast to benign cells (right), metastatic cells (left) penetrate into the gel and disappear inside it, thanks to their unique characteristics
Assistant Professor Daphne Weihs recently achieved a research breakthrough: the unique technology that she developed – a biomechanical method for early detection of metastatic cancer – was approved by the Ethics Committee. This means that the technology that was found to be effective in tests on cell lines will advance to trials with tumor cells collected directly after surgery, in cooperation with Rambam Healthcare Campus.
According to Assistant Professor Weihs, the practical concept is that “during or immediately after a biopsy or surgery on a malignant tumor, the system will enable the medical team to quantitatively evaluate the likelihood of the presence or development of tumor metastases in other organs, and to propose which organ or organs are involved. Such knowledge will make it possible to act at a very early stage to identify and curb these metastases and, moreover, to prevent the primary tumor from metastasizing further.
Cancer is a general name for a wide family of diseases – more than 200 – whose common denominator is that the cell division rate becomes uncontrolled and the cells become immortal. In other words, the cancer mechanism disrupts the normal cell division process and converts it into “wild” and rapid division. Since the cells do not age and do not die, the original, primary tumor expands, invades and takes over more and more nearby tissue. In addition, apart from spreading to its immediate vicinity, a tumor that has become very aggressive “knows” how to send metastases to more distant tissues through the lymph and circulatory systems. Metastases (secondary tumors) are usually more dangerous than the primary tumor because it is difficult to identify them at their inception. When they are detected at an advanced stage, treating them medically is more complicated and the medical prognosis is typically not good.
“In fact, most cancer-related deaths are caused by metastases rather than by the primary tumor, and therefore vast resources are invested in developing methods for early detection of metastases,” explains Assistant Professor Daphne Weihs. “Early detection means timely and more effective treatment. The new approach that we are developing will enable early prediction of the likelihood of the formation of metastases and where in the body their development is probable. This prediction is based on identifying the biomechanics of the primary tumor cells, and does not require us to know the specific genetic makeup of the tumor.”
Diagnostic system developed by Technion professor is to pair with tiny smell-sensitive sensor that can go anywhere
By David Shamah February 3, 2015, 2:05 pm
A patient uses the NaNose breathalyzer (Photo credit: Courtesy Technion)
Writers
David Shamah
An innovative early disease detection system that uses the sense of smell is going mobile.
The NaNose breathalyzer technology developed by Professor Hossam Haick of the Technion will soon be installed in a mobile phone – to be called, appropriately, the SniffPhone. A tiny smell-sensitive sensor will be installed onto a phone add-on, and using specially designed software, the phone will be able to “smell” users’ breath to determine if they have cancer, among other serious diseases.
By identifying the special “odor” emitted by cancer cells, the NaNose system can detect the presence of tumors, both benign and malignant, more quickly, efficiently and cheaply than previously possible, said Haick.
“Current cancer diagnosis techniques are ineffective and impractical,” he said. NaNose technology, he said, “could facilitate faster therapeutic intervention, replacing expensive and time-consuming clinical follow-up that would eventually lead to the same intervention.”
According to research done by Haick’s team, the NaNose system has a 90 percent accuracy rate.
The smartphone device is just a vehicle to implement the NaNose technology that can be taken anywhere and used in any circumstances, including in rural areas of the developing world where bringing in sophisticated testing equipment is impossible.
The plan calls for a chip with NaNose technology to be installed in a device that is attached to a smartphone, and for an app to read the sensor data, analyzing it on the device or uploading it to the cloud for processing.
NaNose technology will be especially useful in battling lung cancer, said Haick. According to US government statistics, lung cancer kills more Americans annually than the next three most common cancers — colon, breast, and pancreatic — combined. The reason, doctors say, is because lung cancer is so difficult to detect. Currently, the only way to detect early-stage lung cancer is through an extensive process involving blood tests, biopsies, CT scans, ultrasound tests, and other procedures — and even then, detection is difficult.
“Mostly the patient arrives for diagnosis when the symptoms of the sickness have already begun to appear,” said Haick, describing the drawbacks in current detection protocols. “Months pass before a real analysis in completed. And the process requires complicated and expensive equipment such as CT and mammography imaging devices. Each machine costs millions of dollars, and ends up delivering rough, inaccurate results.”
Dr. Hossam Haick (Photo credit: Courtesy)
The NaNose-based system, on the other hand, doesn’t require anything more than a patient’s breathing into the device in order to come up with an initial diagnosis. Lung cancer tumors produce chemicals called volatile organic compounds (VOCs), which easily evaporate into the air and produce a discernible scent profile. Haick’s NaNose chip detects the unique “signature” of VOCs in exhaled breath. In four out of five cases, the device differentiated between benign and malignant lung lesions and even different cancer subtypes.
The project is being funded by the European Commission, which has given the consortium developing it a six million euro grant. The developers include universities and research institutes from Germany, Austria, Finland, Ireland and Latvia, as well as Irish cell biology research firm Cellix, with the NaNose system the centerpiece of the technology. That Israeli-developed component will be delivered by an Israeli start-up called NanoVation-GS, a spinoff of the Technion. Professor Haick serves as the start-up’s Chief Science Officer.
“The SniffPhone is a winning solution. It will be made tinier and cheaper than disease detection solutions currently, consume little power, and most importantly, it will enable immediate and early diagnosis that is both accurate and non-invasive,” said Haick. “Early diagnosis can save lives, particularly in life-threatening diseases such as cancer.”
Anyone who knows a person in the midst of chemotherapy is aware that anti-cancer drugs often take a very harsh toll on the body. This is one reason scientists have been trying to develop improved means of drug delivery for years. Now, a Technion research team discovered a way to improve drug delivery to tumors using Nanostructured Porous Silicon (PSi) particles (instead of an IV drip), a method that’s emerging as a promising new platform for drug delivery. In the future, PSi could be used in cancer treatments, potentially offering an alternative to traditional chemotherapy, which is notorious for its agonizing side effects.
The silicon “carriers” used in this study to deliver chemotherapy drugs behave differently in cancerous tumors than they do in healthy tissues. Therefore, the findings could help scientists to design nano-carriers that deliver drugs to tumors, instead of treating patients with traditional, intravenous chemotherapy. However, it would take years to develop and apply this new type of drug delivery method, which would potentially be taken orally.
So far, these nano-silicon “containers” have been studied in vitro – outside of a living organism – rather than in an environment that behaves more closely to that of a tumor in a cancer patient’s body. The Technion research team looked at what happens to PSi particles when they’re injected into the area around the tumor in mice. The significant differences in the area around a cancerous growth and regular healthy tissue have been widely described and studied; however, the effect on these porous silicon “containers,” or carriers, was unknown until now.
Prof. Ester Segal of the Technion – Israel Institute of Technology, who led this joint study with the Massachusetts Institute of Technology (MIT) and the Harvard Medical School, said the team has “shown for the first time that bio-materials in general, and Nanostructured Porous Silicon in particular, behave differently when they are injected (or implanted) at the tumor micro-environment.”
Revolutionizing cancer treatments
Silicon materials could revolutionize treatments in a way that no existing drug delivery does. Prof. Segal tells NoCamels that the silicon containers “could deliver drugs over a long period of time – weeks or even months”, something no existing chemotherapeutic delivery mechanism can do currently.
Cancer cells
The special properties of these porous nano-silicon carriers lie in their large surface area, which can ferry many or large drug molecules. Additionally, due to their biodegradability they’re able to break down into harmless silicic acid, which is expelled through urination. They are also biocompatible, so they do not stimulate any inflammation or clotting. Another benefit to these nano-silicon containers is their versatility. They can be ingested, injected or implanted, and they can be designed to carry a wide range of dosage sizes. In the process of their study, lab members also developed an approach to determining how biomaterials will react in settings more similar to their eventual clinical purpose – treating cancer, for example.
In a separate study, Tel Aviv University scientists recently founda strategy that would stop brain tumor cell proliferation with similar nano-particles. “It is a basic, elegant mechanism and much less toxic than chemotherapy,” TAU’s Prof. Dan Peer said in a statement.
These works underline the importance of such studies in successfully developing bio-delivery materials that will have therapeutic benefits in the near future.
“Nano-skeletons’ (in red) delivered to human tissue infected by prostate cancer. The infected cells are colored in blue (PIP) and green (cytoplasmic); it is possible to see how the ‘nano-skeletons’ reach them
Florida native Dr. Beth Schoen, is part of a team developing a novel platform for delivering anti-cancerous drugs directly to its mark as part of her postdoctoral research at the Technion
Beth Schoen, born in Hollywood Florida, came to the Technion to conduct her postdoctoral research at age 26. In her very limited spare time she plays soccer for the leading all women’s soccer team – Maccabi Hadera – and studies Hebrew. “The Hebrew thing is no simple matter,” she confesses, “but I’m willing to make the effort, because it’s clear to me that Israel is where I want to live.”
Dr. Beth Schoen completed her undergraduate degree at the University of Florida, and her doctorate at Michigan State University in chemical engineering. “My doctoral studies focused on synthetic organic chemistry, particularly on the development of polymers with unique thermodynamic attributes especially resistant to high temperatures. These types of materials are used in part for the production of jet engine parts, body armor and Nomex (used for making fire-resistant gloves and overalls). One of our tasks was to create soft sheets that were not brittle, to be worn to be both bulletproof and fire resistant. It was a theoretical study, but as part of the process I also produced some of these polymers and tested them.”
Dr. Schoen planned to come to the Technion as part of her doctoral studies, but, she adds, “It didn’t work out, so I started to check where I could best fit in here in my future studies.” She decided to join Prof. Marcelle Machluf’s laboratory, at the Faculty of Biotechnology and Food Engineering, “I was eager to move from chemistry to biology and pursue cancer research in particular. I was very glad for the tremendous opportunity that Marcelle gave me in taking me on – perhaps it was because of my experience in nanomaterials and polymers.”
Prof. Marcelle Machluf’s research team consists of 17 female and 3 males students, researchers and technicians working on two main projects: (1) the development of scaffolds to rehabilitate damaged heart-tissue, and (2) the development of new technology to deliver drug treatment to damaged (sick) tissue (specifically related to cancer therapy). In an interview with her she focused on the second project.
“The current treatment for cancer involves radiotherapy and chemotherapy usually administered through intravenous infusion. The cancer drugs available are extremely effective, yet the way they are put to use in present day treatment, they also cause damage to healthy tissues. These are very potent drugs – they are intended to kill cancer cells – and on their way they also end up killing healthy ones.”
“The greatest damage is caused to rapidly dividing cells, which are similar to cancer cells. Hair follicle cells, for example, are a type of rapidly dividing cells and they damage easily from these types of treatment, which explains the hair loss in patients undergoing chemotherapy. Other side-effects include nausea and hearing loss, sometimes even leading to deafness. The drug Cisplatin for example, is a type of chemo drug used to treat various types of lung and breast cancers; some of its side-effects include damage to renal and immune system functioning, putting patients at risk to infections and diseases.”
These impediments are what fuel Prof. Machluf’s drive to develop a new drug delivery platforms capable of delivering anti-cancer drugs directly to the tumor without damaging healthy tissues on its way. “This is the top priority of cancer treatment: to develop a ‘magic bullet’ that target cancer cells,” explains Prof. Machluf. “And our new platform may be the solution to this great challenge.”
The new platform is based on ‘depleting’ specific cells – mesenchymal stem cells – so that there is nothing left of them save for the membrane. This membrane, called a ghost cells can be down sized to nano-vesicles, termed nano-ghosts, which can be loaded with any drug and delivered by injection directly into the blood stream. The immune system falls for the trap and does not recognize the ‘intruder,’ instead it treats these cells as if they were naturally part of the system and sends them to the afflicted area. On the way to their target they do not release the drug they are carrying and therefore do not do any damage to healthy tissues. Only upon reaching the malignant tissue, which they know how to identify, do they break down and secrete their contents at the site of the tumor cells.
This original idea was tested in a long series of experiments, and the results are very impressive: these nano-ghosts are in fact tumor selective, no matter the type of tumor. They ‘dash’ straight to the malignant tissue without emitting their drug on the way and without damaging healthy cells. Moreover, this unique ‘parcel’ increases the effectiveness of the treatment by ten-fold. Animal studies have shown that the employment of nano-ghosts for anti-cancer drug delivery have led to an 80% delay of prostate cancer – an unprecedented rate.
Still, there is a lot of work ahead, as Prof. Machluf’s research team works on improving the mechanism of this novel new platform: some of them are focusing on compatibility with specific drugs while others, like Dr. Beth Schoen, are concentrating on improving the nano-ghosts “This platform must be very precise,” explains Schoen. “It must be able to endure travelling through the entire human body, and release its contents only inside the tumor.”
A growing number of early discovery collaborative agreements are being put in place between large pharma companies and partners in which the rights for assets can reside with a partner, exclusively or jointly. Our corporate screening collection, like many others, was built on the premise that compounds generated in-house and not the subject of paper or patent disclosure were proprietary to the company. Collaborative screening arrangements and medicinal chemistry now make the origin, ownership rights and usage of compounds difficult to determine and manage. The Compound Passport Service is a dynamic database, managed and accessed through a set of reusable services that borrows from social media concepts to allow sample owners to take control of their samples in a much more active way.
The challenges of discovering and developing novel therapeutics have been well documented [1]; and the combination of the ‘low hanging fruit’ of drug targets having been picked off [2] along with the challenge to maintain the pace of new discovery has led to an increase in the complexity of targets and disease pathways in discovery portfolios. Additionally, the pharmaceutical industry has realigned resources away from early R&D [3], making industry more reliant on collaboration with academic groups to share the risks (and rewards) of conducting discovery and early validation efforts [4].
These efforts are frequently captured under the generic term ‘open innovation’, first coined by Henry Chesbrough in 2003 [5]. Since then, a huge variety of definitions for open innovation have been suggested; the authors prefer the definition adopted by the Wellcome Trust: ‘The process of innovating with others for shared risk and reward to produce mutual benefits for each organisation, creating new products, processes or ideas that could not otherwise have been achieved alone, or enabling them to be achieved more quickly, cheaply or efficiently’ [6].
We found that in AstraZeneca (AZ), as is the case across the pharmaceutical industry [7], many more collaborative agreements were being put in place in which the rights for assets could reside with a partner, exclusively or jointly. With more opportunities being investigated to take advantage of our in-house assets, we needed to improve our ability to ensure that compounds subject to a contractual agreement with third parties are managed and used in accordance with AZ’s obligations. Such agreements could mean compounds should be restricted to agreed tests and/or prevented from being shared with other parties.
The problem: compound rights trackingMany corporate screening collections have been built on the premise that collection members that had been generated in house and were not the subject of paper or patent disclosure were proprietary to the company. Collaborative screening arrangements [8] and medicinal chemistry [9,10] now make the origin, ownership rights and contractually governed usage of compounds difficult to determine and complex to manage. When we looked at the compound management tools available within our own organization (or those available from vendors) we found that, in general, solutions were monolithic one-size-fits-all packages and lacked the information granularity necessary to answer key questions around compound-asset rights: compound and sample restrictions were either single sample or all examples from a project; delegation of approval was difficult and all approval was manual; approval tracking and compliance monitoring was difficult and error-prone; in consequence it was difficult to provide partners with a record of requests for ‘their’ samples.
The root cause was that the design of the compound asset infrastructure predated the emergence of shared risk, collaborative, open innovation projects and the infrastructure had been designed against a background where there was a presumption that a company could solely own the rights to the portion of its compound library that was not in the public domain. Together, this created the risk that AZ scientists could unwittingly release the structures of early-stage hits to collaborators that were already the subject of an agreement with another collaborator. Put simply, the infrastructure of material transfer agreements and confidential disclosure agreements was very good at tracking the supply of single compounds but could not cope with the tens to thousands of compounds that needed to be correctly tracked as a result of open innovation collaborations. We aimed to design a dynamic database, managed and accessed through a set of reusable services that borrowed from social media concepts to allow sample owners to take control of their samples in a much more active way. Our design is driven by the vision that a greater number of collaborative agreements are being put in place and that, within those agreements, compound rights can be shared or reside with AZ or the collaboration partner. In turn this drove the need to improve our ability to keep our contractual agreements and progress compounds through approval flows in a timely and efficient manner. In addition to making it easy to record and update details of collaborations, we wanted simply and quickly to add, edit and remove compound assets, as well as to provide fast, reliable and automated approval where possible or to alert approvers where a manual approval is required. Finally, we wanted scientists to be able to determine compound status easily; able to request approval to take specific actions (e.g. testing) within the context of a system that maintained a permanent record.
For the service to function correctly, for each open innovation compound, three pieces of information (metadata) need to be captured and kept up-to-date: (i) who owns any rights to the compound – AZ, the partner or are the rights shared? (ii) Can the compound be tested freely within AZ or does the collaboration agreement indicate that a collaboration coordinator needs to approve test requests? (iii) Has the compound been provided to the partner structure-blinded or has the compound structure been shared with the partner? The service can control ‘trafficking’ as well as maintain a permanent compound ‘life history’. It can be interrogated and receive updates via calls from other systems. Hence, we refer to it as the Compound Passport Service (CPS). Our shared vision and understanding of the underlying metadata allowed us to formulate the main concepts of the system and associated ‘use cases’.
System concepts and use casesCPS centres on assets, which are entities reflecting agreed constraints of compound usage by third parties and are grouped together in asset rights groups (ARG). Additionally, an ARG is a group of rights and rules applied to a number of assets. For each ARG a number of roles can be defined: coordinator – sets up and manages the ARG; delegate – a deputy for the coordinator who can add or remove approvers and add or update assets; approver – a person able to approve or reject requests manually, when the system is unable to make an automatic decision. For each ARG it is also possible to delineate request rules that define which requests can be automatically approved or rejected (e.g. that all compounds within an ARG can be tested in a specific test without any manual approval needed). A user in another system that is fully integrated with CPS becomes a requester when asking for approval to perform a specific action, for example to run a test on a specific compound and CPS responds with the following: ‘approved’, ‘rejected’ or ‘manual approval needed’ (Fig. 1).This structure provides a framework that allows users to take control of their compounds in real-time and in a very granular way. It also has the potential to speed up the flow of compounds through the design-make-test-analyse (DMTA) cycle [11] by giving users the option to set up rules for automatic approval or rejection of tests. To enable these goals, we considered seven critical scenarios (use cases) that the system needed to service (Table 1).
FIGURE 1Compound Passport Service (CPS) concepts and definitions. The CPS is based upon assets, which are entities reflecting agreed constraints of compound usage by third parties, and are grouped (together with the rights and rules applying to the assets) in asset rights groups (ARG). For each ARG a number of roles are defined: coordinator – sets up and manages the ARG; delegate – a deputy for the coordinator who can add or remove approvers and add or update assets; approver – a person able to approve or reject requests manually. Within each ARG it is also possible to delineate request rules that define which requests can be automatically approved or rejected. A user in another system that is fully integrated with the CPS becomes a requester when asking for approval to perform a specific action; the CPS responds with the following: ‘approved, ‘rejected’ or ‘manual approval needed.
More-efficient approval flows and search
The CPS was designed to manage complex compound sharing rules and requirements over the entire lifecycle of a collaboration project. The following is a case history of a recent project that was used to help design a system with the flexibility required. A collaboration project had two chemical series: A and B. Series A originated from screening of the AZ compound collection, and samples were tested by the partner organization in a structure blind format. Synthetic optimisation was performed by AZ but the compounds were never judged to be of sufficient selectivity to merit sharing with the partner. Owing to their origin in a collaboration project, however, series A compounds were not permitted to be tested outside the originating project. Later, the compounds were of no further interest to the project and permitted to be used by AZ projects for any purpose.
Series B originated from the partner organization, and samples were initially shared for testing by AZ in a structure-blind format. After some months of optimization, the chemical structures were shared with AZ but the ownership of the compounds was retained by the partner. Later still, the series was judged of sufficient quality for the intellectual property to be shared jointly between the two organizations. Finally, after the biological target hypothesis was invalidated, notional ownership of the compounds was returned to the partner organization and no further testing was permitted by AZ (Fig. 2).
FIGURE 2The Compound Passport Service (CPS) can be used to manage an asset throughout its lifecycle. In this case study, at the start of the collaboration, compounds were tested at AstraZeneca (AZ) and the collaborator structure-blinded. Over the course of research, SAR failed to develop in series A which became of no further interest and was retained by AZ. Series B provided very productive SAR and, through the course of the collaboration, compound properties were updated in the CPS to note initially that the structures had been shared with AZ, then ownership became shared and therefore the series B compounds were unlocked and freely available for test across both organisations (the figure shows the initial collaboration status).
All of the compound status changes in this scenario are mapped on to three key properties that are captured by the CPS (Table 2). The owner of the ARG is able to change the properties of individual or groups of compounds as required, independently, as the project evolves. Such changes are recorded with time stamps as ‘transitions’, and can be tracked over the lifetime of an ARG. The ability to track all such transitions increases the transparency of compound ownership to AZ and partner organizations, prevents un-authorised testing of samples by other project teams within AZ and enables questions of the provenance of compounds to be easily resolved. When placing test requests in a dedicated in-house requesting tool, the CPS is called and the sample status is displayed. Users might be presented with a warning that corresponding samples are subject to approval. Depending on the permission status, the requester can either decide to seek approval or cancel their tentativerequests. Extreme cases such as auto-rejection (strictly no testing) or auto-approval (green list) are dealt with instantaneously, whereas manual approvals are immediately sought with daily reminders being sent to the approver until a response is obtained. A feature much appreciated by users is that the system sends an approval email to authorisers giving them the full context of the requests to ensure efficient decision making rather than having to access the CPS to gain the wider context.
Green lists (leading to auto-approvals) are crucial to ensure no impact of sample restrictions on the DMTA cycle. In the case of required manual approvals, the impact of delay is minimised by the creation of project delegates. Green list assays refer to tests agreed with the partner and typically include project assays [primary target, selectivity, in vitro drug metabolism pharmacokinetics (DMPK), among others]. Similarly, a green list of requesters typically includes project members who are fully aware of the collaboration. Delegates have the same approval rights as primary authorisers and requests come to all independently, so that the first person to approve them releases the samples for testing.
Interface with other servicesThe envisioned central role and future extensibility of asset rights management led to the rapid conclusion that the compound passport solution needed to be delivered as a service [12]. The adoption of a service-orientated architecture has provided a flexible and reusable set of business services that provide access to and management of the compound passport database. Additional commodity services provide master data for projects, people and compounds (Fig. 3).
FIGURE 3Service-orientated architecture provides a flexible and reusable set of business services that provide access to and management of the Compound Passport Database. Additional commodity services provide master data for projects, people and compounds. In this way, the Compound Passport Service (CPS) sits at the centre of a web of independent services controlling compound registration, distribution and test approval. Utilisation of reusable services allows integration with new systems as they become available in the future.
….
Impact on open innovationSince the CPS was launched in 2014, it has been uploaded with metadata relating to 15,000–20,000 assets, and compounds are being added almost daily. The ability to track ownership rights along with more-efficient test approval has already enabled faster and more-efficient approval flows. Additionally, in considering whether to unblind the structure of a HTS hit series, we have also been able to identify that more than one external party had an interest in the chemical equity. Based upon an understanding that SAR would probably diverge as potency against the different targets was optimised, we have been able to adopt a risk-management approach to allow both partners to proceed with the investigation and possible optimization of the shared chemical start point.
Medical Breakthrough: Israeli Researcher Predicts Where Cancer Will Spread
Reporter: Evelina Cohn Budu, PhD
An innovative technology developed in Israel may soon be able to predict the spread of cancer from one organ to another, potentially saving the lives of millions of people around the world.
The technology, developed at Israel’s Technion – Israel Institute of Technology, has been proven in preliminary laboratory trials, and is now entering into advanced testing using cells from patients undergoing surgery.
Assistant Professor Dr. Daphne Weihs has developed a unique biomechanical method for the early detection of metastatic cancer (a cancer that has already spread). At the metastatic stage, the original, primary tumor expands, invades and takes over more and more nearby tissue. A tumor that has become very aggressive “knows” how to send metastases to more distant tissues through the lymph and circulatory systems.
Metastases (secondary tumors) are usually more dangerous than the primary tumor because it is difficult to identify them at their inception. When they are detected at an advanced stage, treating them medically is more complicated and the medical prognosis is typically not good.
Podcast Review: Quiet Innovation Podcast on Obtaining $ for Your Startup
Reporter: Stephen J. Williams, Ph.D.
I wanted to highlight an interesting interview (What it Really Takes to Get Money for Your Startup) with David S. Rose, serial entrepreneur and Founder and CEO of Gust.com, which is a global collaboration platform for early stage angel investing, connecting hundreds of thousands of entrepreneurs and investors in over 75 countries. The interview with David and CFA John P. Gavin was broadcast on the podcast Quiet Innovation (from PodCast Addict @Podcast_Addict) from. I had tweeted it out on my Twitter account below (see the http link)
… but will include some notes from the podcast here. In addition you can link to the podcast directly using the links below:
David Rose discusses how there are hundreds of thousands of new ideas, some which are great some which are not… having an idea may be an initial step but for an investor to even consider your idea it is more important to have
EXECUTION
This is what David feels is critical to investors, such as himself, to decide whether your idea is investable. A startup needs to show they can accomplish their goal and show at least a rudimentary example of this, whether it is putting up a website or writing up a design blueprint for a new widget. He says starting a business today (either tech or manufacturing) requires a lot less capital than years ago (unless you are starting a biotech). He gives an example of internet startups he had founded in the 90’s versus today… in the 90’s you needed $2 million… today you can do it for $2,000. But the ability to show that you can EXECUTE this plan is CRITICAL.
David sites three aspects which are important to investors:
Integrity – Be humble about yourself. He says there are way too many people who claim ‘our idea is the best’ or ‘we do it better than anyone’ or ‘we are the first to have this idea’. As he says Jeff Bezos of Amazon was not the first to have the idea of selling books over the internet, he just EXECUTED the plan extremely well.
Passion- Investors need to see that you are ‘all in’ and committed. A specific example is angels asking how much money have you put into your idea (skin in the game)
Experience- David says there are TWO important types of experience in developing startups and both valid. The first is how many startups have you done and succeeded and the second is how many startups have failed. He says investors actually like if you have failed because they are learning experiences, just as valuable if not more than having startups always succeed. Investors need to know how you can deal with adversity. All three points goes back to execution.
David Rose gave some reading suggestions as well including
Eris Reese’s post The Lean Startup in his blog StartUpLessonsLearned – being frugal (gets back to what he said about not needed as much capital as you would think i.e. Don’t Burn Through the Cash) and also get metrics on your startup or idea (as long as you have the IP). He suggests taking out an ad to see what the interest is out there. You can measure the clicks from the ad and use that as a marketing tool to potential investors i.e. Getting Feedback
Some other posts on this site about Investing and Startups include:
Protecting Your Biotech IP and Market Strategy: Notes from Life Sciences Collaborative 2015 Meeting
Achievement Beyond Regulatory Approval – Design for Commercial Success
Stephen J. Williams, Ph.D.: Reporter
The Mid-Atlantic group Life Sciences Collaborative, a select group of industry veterans and executives from the pharmaceutical, biotechnology, and medical device sectors whose mission is to increase the success of emerging life sciences businesses in the Mid-Atlantic region through networking, education, training and mentorship, met Tuesday March 3, 2015 at the University of the Sciences in Philadelphia (USP) to discuss post-approval regulatory issues and concerns such as designing strong patent protection, developing strategies for insurance reimbursement, and securing financing for any stage of a business.
The meeting was divided into three panel discussions and keynote speech:
Panel 1: Design for Market Protection– Intellectual Property Strategy Planning
Panel 2: Design for Market Success– Commercial Strategy Planning
Panel 3: Design for Investment– Financing Each Stage
Keynote Speaker: Robert Radie, President & CEO Egalet Corporation
Below are Notes from each PANEL Discussion:
For more information about the Life Sciences Collaborative SEE
Panel 1: Design for Market Protection; Intellectual Property Strategy Planning
Take-home Message: Developing a very strong Intellectual Property (IP) portfolio and strategy for a startup is CRITICALLY IMPORTANT for its long-term success. Potential investors, partners, and acquirers will focus on the strength of a startup’s IP so important to take advantage of the legal services available. Do your DUE DIGILENCE.
Panelists:
John F. Ritter, J.D.., MBA; Director Office Tech. Licensing Princeton University
Panel Moderator: Dipanjan “DJ” Nag, PhD, MBA, CLP, RTTP; President CEO IP Shaktl, LLC
Notes:
Dr. Nag:
Sometimes IP can be a double edged sword; e.g. Herbert Boyer with Paul Berg and Stanley Cohen credited with developing recombinant technology but they did not keep the IP strict and opened the door for a biotech revolution (see nice review from Chemical Heritage Foundation).
Naked patent licenses are most profitable when try to sell IP
John Ritter: Mr. Ritter gave Princeton University’s perspective on developing and promoting a university-based IP portfolio.
30-40% of Princeton’s IP portfolio is related to life sciences
Universities will prefer to seek provisional patent status as a quicker process and allows for publication
Princeton will work closely with investigators to walk them through process – Very Important to have support system in place INCLUDING helping investigators and early startups establish a STRONG startup MANAGEMENT TEAM, and making important introductions to and DEVELOPING RELATIONSHIOPS with investors, angels
Good to cast a wide net when looking at early development partners like pharma
Good example of university which takes active role in developing startups is University of Pennsylvania’s Penn UPstart program.
Last 2 years many universities filing patents for startups as a micro-entity
Comment from attendee: Universities are not using enough of their endowments for purpose of startups. Princeton only using $500,00 for accelerator program.
Cozette McAvoy: Mrs. McAvoy talked about monetizing your IP from an industry perspective
Industry now is looking at “indirect monetization” of their and others IP portfolio. Indirect monetization refers to unlocking the “indirect value” of intellectual property; for example research tools, processes, which may or may not be related to a tangible product.
Good to make a contractual bundle of IP – “days of the $million check is gone”
Big companies like big pharma looks to PR (press relation) buzz surrounding new technology, products SO IMPORTANT FOR STARTUP TO FOCUS ON YOUR PR
Ryan O’Donnell: talked about how life science IP has changed especially due to America Invests Act
Need to develop a GLOBAL IP strategy so whether drug or device can market in multiple countries
Diagnostics and genes not patentable now – Major shift in patent strategy
Companies like Unified Patents can protect you against the patent trolls – if patent threatened by patent troll (patent assertion entity) will file a petition with the USPTO (US Patent Office) requesting institution of inter partes review (IPR); this may cost $40,000 BUT WELL WORTH the money –BE PROACTIVE about your patents and IP
Panel 2: Design for Market Success; Commercial Strategy Planning
Take-home Message: Commercial strategy development is defined market facing data, reimbursement strategies and commercial planning that inform labeling requirements, clinical study designs, healthcare economic outcomes and pricing targets. Clarity from payers is extremely important to develop any market strategy. Develop this strategy early and seek advice from payers.
Panelists:
David Blaszczak; Founder, Precipio Health Strategies
Terri Bernacchi, PharmD, MBA; Founder & President Cambria Health Advisory Professionals
Paul Firuta; President US Commercial Operations, NPS Pharma
Panel Moderator: Matt Cabrey; Executive Director, Select Greater Philadelphia
Notes:
David Blaszczak:
Commercial payers are bundling payment: most important to get clarity from these payers
Payers are using clinical trials to alter marketing (labeling) so IMPORTANT to BUILD LABEL in early clinical trial phases (phase I or II)
When in early phases of small company best now to team or partner with a Medicare or PBM (pharmacy benefit manager) and payers to help develop and spot tier1 and tier 2 companies in their area
Terri Bernacchi:
Building relationship with the payer is very important but firms like hers will also look to patients and advocacy groups to see how they respond to a given therapy and decrease the price risk by bundling
Value-based contracting with manufacturers can save patient and payer $$
As most PBMs formularies are 80% generics goal is how to make money off of generics
Patent extension would have greatest impact on price, value
Paul Firuta:
NPS Pharma developing a pharmacy benefit program for orphan diseases
How you pay depends on mix of Medicare, private payers now
Most important change which could affect price is change in compliance regulations
Panel 3: Design for Investment; Financing Each Stage
Take-home Message: VC is a personal relationship so spend time making those relationships. Do your preparation on your value and your market. Look to non-VC avenues: they are out there.
Panelists:
Ting Pau Oei; Managing Director, Easton Capital (NYC)
Manya Deehr; CEO & Founder, Pediva Therapeutics
Sanjoy Dutta, PhD; Assistant VP, Translational Devel. & Intl. Res., Juvenile Diabetes Research Foundation
In 2000 his experience finding 1st capital was what are your assets; now has changed to value
Notes:
Ting Pau Oei:
Your very 1st capital is all about VALUE– so plan where you add value
Venture Capital is a PERSONAL RELATIONSHIP
1) you need the management team, 2) be able to communicate effectively (Powerpoint, elevator pitch, business plan) and #1 and #2 will get you important 2nd Venture Capital meeting; VC’s don’t decide anything in 1st meeting
VC’s don’t normally do a good job of premarket valuation or premarket due diligence but know post market valuation well
Best advice: show some phase 2 milestones and VC will knock on your door
Manya Deehr:
Investment is more niche oriented so find your niche investors
Define your product first and then match the investors
Biggest failure she has experienced: companies that go out too early looking for capital
Dr. Dutta: funding from a non-profit patient advocacy group perspective
Your First Capital: find alliances which can help you get out of “valley of death”
Develop a targeted product and patient treatment profile
Non-profit groups ask three questions:
1) what is the value to patients (non-profits want to partner)
2) what is your timeline (we can wait longer than VC; for example Cystic Fibrosis Foundation waited long time but got great returns for their patients with Kalydeco™)
3) when can we see return
Long-term market projections are the knowledge gaps that startups have (the landscape) and startups don’t have all the competitive intelligence
Have a plan B every step of the way
Other posts on this site related to Philadelphia Biotech, Startup Funding, Payer Issues, and Intellectual Property Issues include:
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Aashir Awan, Phd
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Alan F. Kaul, PharmD., MS, MBA, FCCP
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