HIGHLIGHTS

Unlocking the Future
of Precision Medicine

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Oct. 27 2020

ARTICLE

The Breakthrough Technology
in Precision Medicine for Cancer 

With more than 200 types and subtypes, cancer is not a single disease. In the last decade, we have realized the need to shift away from a one-size-fits-all approach towards a more targeted tailored therapy, or “precision medicine.”

As a new paradigm that enables better health outcomes, precision medicine is extremely promising. Precision medicine therapies are more targeted and developed in accordance with individual detailed analysis, instead of treating them as ‘typical patients’.

The field that has witnessed the maximum impact of precision medicine developments is oncology.
In 2018, 90% of top-marketed approved precision treatments were cancer therapies.

However, they are still not absolutely personalized therapies - they don’t cater to individuals, but they do make for more detailed patient stratification.

Why Precision Medicine
has Failed to Deliver

Since its inception in 1990s, DNA sequencing ushered in the precision medicine revolution for cancer treatment, and yet, there is a lot that needs to be done. While being hailed as a treatment strategy that hold immense promise, precision medicine, as we know today, suffers from many issues.

The three problems that have caught the attention of researchers are that (a) precision medicine-based therapies work for only a minority of cancer patients, even though these patients have the mutations that the therapies target, (b) the drugs that initially work typically stop working after a relatively short period of time, ranging from a few months to a few years, and (c) most targeted therapies occasionally work for patients who do NOT have the targeted mutation. There is clearly something we do not understand about how these targeted therapies work. 

One of the reasons why many targeted therapies also fail is that cancers are often heterogeneous – many cancers are a mix of at least 5 different cancers.

If each cancer patient has a unique mixture of multiple different cancers, and that mixture is changing over time and in response to selective pressures from therapies that are effective against some but not all of the different cancers, how can we develop effective personalized therapies for each cancer patient?


There are two other approaches within precision medicine that can create a truly personalized treatment for every individual patient. One is by modification of each patient’s T-cells (which is prohibitively expensive and frequently toxic).
The second emerging paradigm of personized medicine for cancer uses a very old and low-tech method to find a combination of therapies that target each of the multiple types of cancers in each patient – trial and error. This approach is not practical as it takes a long time, the drugs are toxic to the body and the cost is prohibitive.

How the Functional Testing
Approach Holds Promise

One solution that has been used by a few companies is “functional testing” - to try the drugs OUTSIDE the patient rather than INSIDE. This means removing some of the cancer cells from the patient and applying the drugs to these removed ("ex vivo") cancer cells. In this manner, hundreds of drugs can be tried out for their efficacy in killing these cells.

This approach could identify effective cancer drugs and drug combinations for patients with no biomarkers, without imposing any toxicity during the testing process.

There is still a gap that needs to be filled when it comes to offering the right therapy for every patient. While functional testing approach seems practical, cancer researchers have tried and failed for many years to create a reliable ex vivo cancer drug effectiveness test. 

The Travera Approach

Recent advances in live-cell laboratory procedures and measurement tools have made this ex vivo trial and error approach possible. Travera is pioneering a new approach to functional testing that offers the promise of identifying the personalized combination of drugs that will target each patient's uniquely heterogeneous cancer. A new ultra-sensitive technology developed at MIT, the SMR (Suspended Microchannel Resonator) technology, allows monitoring of cell growth by measuring individual cell mass. Dana Farber Cancer Institute has collaborated with MIT and Travera to provide acute cell sensitivity testing with SMR technology and has applied it successfully to patient cells, cell lines and PDXs.

The technology, developed at the Manalis lab of the Massachusetts Institute of Technology’s Koch Institute for Integrative Cancer Research makes use of precise frequency measurements that enables the calculation of the weight of the cancer cells with sub-picogram accuracy. By measuring the mass response (change in weight) of the ex vivo cancer cells of a patient in response to various cancer drugs using a Micro Electro Mechanical (MEMS) device, the drugs that would work for that patient may be determined.

Depending on the type of tumor, physicians collect patients’ cancer cells (from blood, bone marrow and solid tumors) which are purified, separated and then administered various drugs – single or in combination. Monitoring the mass response of the cells to the drugs is the key to finding out the suitability of a particular drug that can treat the heterogeneous cancers of every patient.

This functional testing with SMR is fast too, and drug response can be evaluated in a single day, instead of the weeks it generally takes for test results to arrive. 

This testing is safe, since it requires very few cells, which can be collected with simple needle biopsies instead of invasive surgeries. Moreover, the measurements are extremely precise, with accuracy of one part in ten thousand.

Challenges to Adoption
of Precision Medicine

According to the annual Precision Medicine Study by Definitive Healthcare, a leading provider of data, intelligence and analytics provider in the healthcare market, the biggest challenge (at 28%) that precision medicine faces is that of cost (since genome sequencing is quite expensive), followed by obtaining coverage from payers (20%). Many healthcare organizations are wary of entering the realm of precision medicine because of the lack of expertise – precision medicine is based on complex clinical processes and demands extensive disease information, besides a great deal of support from secondary staff.

The recent economic problems brought on by the global Covid-19 pandemic has forced a relook and pivoting of priorities and set programs. Resources are being allocated to find better diagnostic tests and vaccines for the novel coronavirus. However, despite all of these challenges, Travera has continued its march towards development and fine-tuning this technology in a bid to find an effective solution to the growing menace of cancers around the world.

How Travera’s Approach has Created
a “Universal Biomarker”

Cancer biomarkers have been the guiding factor for oncologists to treat cancer patients. However, biomarkers may not always be present in every cancer patient, and even genomic biomarkers are not always precise. There is a need to explore and develop better biomarkers that can be applied to more patients and produce better outcomes.

A universal biomarker, that will be true for all patients, might seem unlikely, but by measuring weight change rather than genomic biomarkers, Travera’s testing approach effectively incorporates all genomic and proteomic bio-markers, both known and unknown, as well as a myriad of other known and unknown factors including epigenetic, metagenetic, environmental, and other factors that affect a cancer cell’s response to a cancer drug. The weight change of ex vivo cancer cells in response to cancer drugs may become a "universal biomarker," shared by virtually all cancer patients, and applicable to virtually all cancer drugs.

Myeloma is a cancer that often changes with time. In case of a relapse, it is never the same as it was the first time around.

In such a scenario,  the possibility of weighing the cells and determining the right therapy, irrespective of genomic changes that might have taken place, is a truly revolutionary idea.

Travera’s clinical study portfolio comprises of 4 cancers - multiple myeloma, acute myeloid leukemia, non-small cell lung cancer and breast cancer.

THE WAY FORWARD

Travera has not only successfully developed a precise approach to cancer treatment; it has also established strong relations with some of the most reputed academic medical centers. The complex processes – medical, operational and several others- are ably handled by its management and advisory team that consists of several experts, and especially Clifford Reid, the founding CEO of Travera.

With a S.B. in Physics from MIT, an MBA from the Harvard Business School, and a Ph.D. in Management Science and Engineering from Stanford University, Dr. Reid is one of the prominent leaders of the biotech industry. Prior to founding and leading Travera, Dr. Reid was the founding Chairman, President and Chief Executive Officer of Complete Genomics, a NASDAQ-listed leading company (now part of BGI Group) that develops whole human genome DNA sequencing technologies and services. He is on the Visiting Committee of the Biological Engineering Department at the MIT, a member of the MIT Corporation Development Committee, and an advisor to Warburg Pincus.
 
Under his able leadership and benefitting from his immense experience and deep industry insights, Travera is all set to commercialize a radically new method that holds the potential to transform many applications in oncology and immunology.