Challenges and Opportunities in Treating Cognitive Disorders

Posted on May 14, 2018 by Hank Safferstein

By Hank Safferstein, Ph.D., J.D.
PLSG Executive In Residence

Cognitive disorders, such as Alzheimer’s dementia, are devastating and will put an increasing strain on our healthcare system as the population ages. As of February 2016, there were approximately 174 drugs in clinical development, with only 5 marketed therapeutics. This disparity, in large part, is due to difficulties demonstrating efficacy in clinical trials.

Efficacy can be difficult to demonstrate for two primary reasons. First, Alzheimer’s patients likely comprise a heterogeneous population where the disease can stem from disparate pathologies. Patients are segmented primarily on the presentation of symptoms. This is important because two patients with similar symptoms may have dysfunction in different pathways, meaning a therapeutic may work for one patient but not the other. When an investigational new drug is given to a specific patient population, it provides more power to a clinical trial. Second, traditional outcome measures are centered around cognition, a relatively “soft” and imprecise clinical endpoint. Cognition is considered “soft” because it naturally changes from morning to evening, from day to day, and between individuals. Additionally, patients in both the placebo and drug groups learn these cognitive tasks over the course of a clinical trial. Identification of factors that consistently report the severity of the disease across time and individuals will also provide more power to a clinical trial.

Identification of Alzheimer’s specific biomarkers can bridge these challenges. Biomarkers can provide important information on the presence and progression of the disease. An ideal biomarker can effectively link a drug’s mechanism of action to its intended effects on disease pathways. Therefore, instead of relying solely on cognitive function, drug efficacy can be based on changes in expression of molecular biomarkers. Likewise, these biomarkers can be used to segment the population based on the presence or expression of specific biomarkers instead of subjective measures of symptoms. Failure rates in Alzheimer’s clinical trials could be reduced significantly if patients were segmented based on molecular profiling.

Our challenge, to both clearly measure outcomes and segment patient populations, boils down to a core need to identify specific biomarkers of these diseases. Plasma, cerebrospinal fluid (CSF), and imaging (MRI, PET) biomarkers have the potential to improve diagnosis, stratify or otherwise segment patients, and provide measures on which to track disease progression and the effects of therapeutic and lifestyle interventions. There is a real need for the successful translation of biomarker data generated through the use of mass spectrometry, immunoassays, and imaging into patient endophenotypes. Researchers believe this will happen, but the question remains: Will regulatory agencies accept biomarkers as clinical endpoints?

The PLSG continues to conduct outreach and engage in direct involvement with life sciences innovators working to better understand and treat these cognitive disorders.

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Private vs Government (Public) Funded Medical Device and Therapeutic Development

Posted on September 13, 2016 by Hank Safferstein

A perfect, unflawed system in any business sector is virtually unachievable, and the biotechnology and therapeutics industries are no exception. Although we are innovating and making strides to end what were once thought of as incurable diseases, we still do not have one single agreed upon way of funding the research and development of drugs and medical devices.

Week after week, new devices and drugs are approved by the FDA, but where does all the money that funds these life science investments come from? Part of it comes from government grants through the National Institute of Health. More specifically, $32.3 billion annually is awarded through nearly 50,000 grants reaching over 300,000 scientists throughout the country. The rest of the estimated $117 billion comes from industry, foundations and other private sectors. And although $117 billion sounds like a lot of money, it only accounts for 0.7 percent of the gross domestic product while the healthcare industry provides 17 percent of the nation’s economy.

A recent U.K. government review stated that the future of research and development funding should be done through the government itself. With a backing from former Goldman Sachs chief economist Jim O’Neill, not only did the research say that it should be funded this way, but that those who don’t participate should be fined. Although this may seem like a good idea, there are many reasons why our current system benefits both private and government industries.

Government Funding Only

A government funded only system sounds like a good idea, but in reality it may take away the drive that pushes many to support the industries. If all of the industry’s money was distributed this way, research studies that may have not gotten a significant amount of money to use would then be awarded funds. Although this may seem like a win-win situation, it would create a much less competitive industry. You would no longer need to be the best, most precise researcher possible, because quite frankly you’d never be given a deserved reward for the service provided.

Private Funding Only

On the other hand, a system regulated only by private funding would be equally detrimental. One good thing that it would create is competitiveness. The best and the brightest would be rewarded for their work, but would they strive to help the next generation like they do now? It would create an industry run by the wealthiest, only trying to help them get richer and solve only their problems. Poverty in our world has already been one of the leading factors of the spread of disease, and if the research and development went private, this issue would only grow substantially. Each newly developed life science products could become a monopoly, similar to what happened when Martin Shkreli, former CEO of Turing Pharmaceutical, hiked up prices on his company’s drug, Daraprim, an antiparasitic commonly used to treat HIV patients. The government side of the industry is what keeps the private in check, just as congress is designed to do for the president.

Finding Balance

The key to addressing the seemingly intractable diseases of our time is to strike the appropriate balance between public and private financing.

For Government, there is simply too much focus on academic science and not enough on small business, one of the major engines of innovation in the drug and device sector. For example, only a very small fraction of the total NIH funding goes to small businesses through SBIRs, STTRs, UO1s and RO1s.

From the private investment side, while angel investors have stepped up to the plate to fund innovation, venture and strategics have moved away from the risk and created huge funding gaps that, in the end, only hurt them in the long term through a complete loss of innovation in the pipeline.

So how do government and private funders pivot to drive research and development forward? Government funding needs to expand their effort towards funding the science beyond the bench. The private sector funding also needs to modify their investment models to allow for the risk in investing to the research. If both sides are able to support the translational process on the road to commercialization than more funds will become available to life sciences companies thus incentivizing them to research and develop life saving solutions to the public.

3 Groundbreaking Areas of Innovation by Biotech Entrepreneurs

Posted on April 20, 2016 by Hank Safferstein

Biotechnology has been a traditionally risky investment. As Lori Kozlowski stated in Forbes, biotech requires large sums of money without any guaranteed outcome — a high risk for a potentially high reward. It can be difficult for investors to reconcile that risk when there are other avenues that yield a safer return on investment. Although that might seem like common sense, it does not reflect reality.

While the risk may be a huge hinderance for academic institutions or pharmaceutical companies, entrepreneurs and startups can innovate in biotech with more flexibility. Entrepreneurs can shift focus and adapt to new information much more quickly than larger institutions, allowing their work and that of their scientists to have a more meaningful impact on the company and project. They are able to avoid false positives or end failing projects more easily than their larger competitors, allowing for more promising results.

This versatility is why startups have been responsible for major breakthroughs in biotechnology in recent years — and, if this continues, for years to come. Here are some of the biggest biotech innovations from the last five years.

Precision Medicine

Since the advent of the $1,000 genome, the medical community has been abuzz about the prospects of individualized treatments. That excitement has translated into President Obama’s precision medicine initiative and an increase of genomic-driven startup activity. Last year saw a remarkable increase in venture funding for biotech and genomic startups — from accelerators and big name investors like Google and the Bill and Melinda Gates Foundation — which seems likely to continue into this year.

While big pharmaceutical companies are also making strides in precision medicine, startups have demonstrated an ability to specialize and take advantage of the cloud that allows them to innovate. Helomics brings this approach to cancer treatment by allowing for the comparison of live and archived cancer cells. This gives doctors a clear picture of the cancer’s development and helps them provide better treatment for the individual patient.

Biomarkers

The identification and study of biomarkers has been closely tied to precision medicine. They play an important role in medicine and the development of pharmaceuticals, but that is far from the end of their usefulness. As the Innovation Zone at the BIO International conference has shown, biotech startups are using biomarkers to monitor water quality and as a part of bioprocess control. Pittsburgh-based Applied Isotope Technologies is monitoring biomarkers for both medical and environmental improvements.

Visualization & Prediction

As microscopes and computers continue to become more powerful, startups are able to develop more powerful and less invasive tools for observation and prediction. Cells can be analyzed, digitally recreated and manipulated, and studied in fine detail on screens. Immunetrics brings this approach to acute and chronic inflammatory diseases by rendering mathematical models of cells and patient populations.

Others take a more microscopic approach. Spectragenetics — who recently joined IntelliCyt’s Technology Alliance Partner Program — uses particles that selectively emit fluorescence in proximity to other particles to assist in identification. This allows for greater precision in therapeutic development. The arrays that Spectragenetics uses for this process are licensed from Sharp Edge Labs, who use their technology to develop unique arrays that help identify treatment possibilities. Recently, Sharp Edge received a grant from the Michael J. Fox Foundation to apply their methods to Parkinson’s Disease.

The pace of innovation in the biotech space does not seem to be slowing down, and we are proud to support western Pennsylvania biotech companies. What will be the next big area of innovation in biotechnology?

How Innovative Startups are Changing the Way Diseases are Diagnosed

Posted on June 5, 2015 by Hank Safferstein

While the world of healthcare is one of constant change and innovation, the process of diagnosing diseases can still be difficult. The number of tests administered to any given patient and the wait time for those results can be frustrating. Each year billions of tests are administered, but leave much to be desired in terms of accuracy and patient satisfaction. There is still need for greater innovation.

Some of the most exciting diagnostic developments are coming from health startups. These small companies are able to focus on inefficiencies that may be overlooked in testing, diagnosis, monitoring, or treatment. Their efforts allow doctors to reach more accurate diagnoses and offer more effective treatments. The more this process can be improved, the better our patients’ outcomes.

Here are a few of the most important ways these startups are improving diagnostics.

A Personal Touch

Disease diagnoses tend to follow patterns based on the most successful treatments, but this approach can be ineffective for some patients. Advancements in medical screening technology and DNA sequencing have made it much easier to address this problem. Health startups like RedPath Integrated Pathology are poised to build on these developments to benefit patients and healthcare providers.

RedPath’s PathFinderTG tests address ambiguities in cancer diagnoses. PathFinderTG is a molecular test that reveals genetic markers and other factors that are missed by other tests. Based on patient DNA, this information helps doctors better determine whether or not a tumor is benign or malignant and recommend the most effective treatment.

Simplification

Some diagnostic methods subject patients to a battery of tests or put analysts through hours upon hours of manual processing of these tests. And the results might not even lead to a patient-specific treatment. Why put patients and laboratories through so much in order to reach a general diagnosis and treatment? Cernostics is changing the game by simplifying the testing process.

Cernostics’ Tissue Cypher Technology whittles that battery of tests down to one. Much like RedPath, Cernostics uses a molecular-level biopsy to better assess the cancer risk of patients with Barrett’s esophagus━one simple test with personal results. They even want to expand testing to lung, breast, and colon cancers. And with $1.4 million in their Series B startup funding round, along with prestigious academic partnerships, Cernostics is poised to make a huge impact.

Creativity

Sometimes the best way to innovate is to find a unique use for something seemingly mundane. Successful health tech startups, whether out of vision or necessity, have a knack for finding such uses. By using common technology in unexpected ways, even the most routine aspects of healthcare can be revolutionized.

For example, Intelomed ’s CVInsight makes use of one of today’s most ubiquitous and fashionable technologies━bluetooth━to vastly improve patient monitoring. A single bluetooth sensor, worn on the patient’s forehead, gives healthcare providers real-time updates to physiologic changes. The sensors pick up the slightest unfavorable change, helping alert doctors to potential events and prevent them from ever happening.

Developments by startups like these are going to greatly improve healthcare. Ambiguities in diagnosis will be clarified, effective and appropriate treatments will be found faster, and life-threatening events will be avoided. All of this will drive down costs and boost patient satisfaction. RedPath Integrated Pathology, Cernostics, and Intelomed are all part of the incubator at the Pittsburgh Life Sciences Green house, proud supporters of life science innovation.