Predicting patient response to immunotherapy treatment

Dr. Ofer Sharon is a physician and entrepreneur with more than 17 years of experience in the oncology drug development industry. He is the CEO of OncoHost, a global leader in host response profiling for improved personalized cancer therapy. Here, Sharon tells SelectScience^® about OncoHost's cutting-edge new technology designed to analyze and predict patient response to immunotherapy treatment, to gain a better understanding of the mechanisms of resistance and provide potential solutions to combat this.

Immunotherapy for cancer treatment is on the rise. What are the opportunities and challenges?

Indeed, immunotherapy is on the rise. The mechanism of action coupled with good clinical results has initiated a wave of optimism, and clinical trials have begun assessing immunotherapy in many clinical indications. As more companies enter the immunotherapy markets, reality has hit us as we see more failures in clinical trials. A better understanding of the safety profiles of immunotherapy has led to a more cautious approach towards the therapy, as we understand that as with any treatment, we have to balance both safety and efficacy. While the adverse event profile is very different from chemotherapy, for example, we still need to consider it both in terms of the safety of our patients, as well as the cost of managing these adverse events. Prof. James Allison, one of the pioneers of immunotherapy and Nobel Prize winner for his achievements in the field, was quoted saying that, “The biggest challenge in immunotherapy today is to learn why it helps some patients but not others – and how to combine it with traditional therapies to improve outcomes and reduce side effects.”

The high failure rate in immunotherapy phase 3 trials pose another challenge. As the common understanding is to try and direct the treatment to the most inclusive patients’ populations, we see today that many trials fail for exactly that reason. As with any treatment modality, we know today that in most cases immunotherapy is not a one-size-fits-all solution for all patients, and we need to be able to identify the right patient that will benefit from treatment. The problem? There are no good biomarkers out there.

The economic challenge is related to the above. On one hand, we want to help all patients, giving them the chance (even if it’s a low one) to respond to treatment. On the other hand, the high cost of immunotherapy, combined with the high number of patients, causes a potential financial burden on health systems that is basically non-sustainable.

The bottom line is, that in order to improve outcomes, safety, and economic feasibility, we need to identify the patients that will benefit from treatment from those that won’t.

OncoHost is developing cutting-edge technology to characterize, analyze and predict patient response to immunotherapy treatment. Tell us about your technology and mission.

Precision medicine is at an inflection point. As patients, clinicians, and payors realize the need to treat selectively and not empirically, diagnostic companies, academia and pharmaceuticals are looking for biomarkers that will identify the right patients for immunotherapy treatment.

The vast majority of companies out there are looking for biomarkers by analyzing the interaction between the therapy and the tumor. For example, PD-1 levels for anti PD1 medications. The results are surprisingly disappointing. We see a good correlation only in some of the tumors for some of the patients. This approach for the search of good biomarkers makes sense, however, it ignores the fact that the interaction between the drug and the tumor takes place within a complex biological system -the patient themselves - and indeed the predictive capability of biomarkers today is limited at best.

OncoHost takes a very different approach. Based on over 15 years of research in the Israeli Institute of Technology, our inventor, Prof Yuval. Shaked, discovered that the host response i.e. the way the body is responding to the anti-cancer treatment, may actually facilitate tumor growth and progression. This discovery led to our approach, which involves analyzing the host response in order to predict response to treatment.

In order to analyze the host response and create a prediction, OncoHost developed a platform called PROphetTM, that combines the analysis of over 1,000 proteins that are present in our blood in response to treatment. Using sophisticated machine learning tools, we are able to create an accurate response prediction, as well as provide clinicians with actionable clinical insights on the mechanisms of resistance to treatment and potential solutions.

Our mission is to make host response profiling a routine part of the patient’s assessment, as well as monitoring during treatment in order to identify who will actually benefit from it. This will improve outcomes, reduce costs, and minimize unnecessary adverse events.

How will your approach impact patients, pharma, and the broader oncology community?

In the short term, oncologists will be able to use our test in order to understand whether their patients will respond to therapy or not, thereby gaining valuable information of mechanisms of resistance and potential solutions. This is a layer of information that is missing today. For patients, this means knowing more and better understanding of the disease and the journey ahead of them, which is very important when dealing with a severe illness with many unknowns and confounders. However, most important to note is the fact that personalizing the treatment offers better clinical outcomes for both patients and physicians. For payors and health systems, personalized care offers sustainable, value-based care that will target the right patients instead, avoiding the expensive one-size-fits-all approach.

OncoHost recently opened a new lab – can you tell us about it? 

We recently opened a proteomic lab that can analyze blood samples from our clinical sites in Israel and Europe. A similar lab is operating with our US partner, RayBiotech, in Atlanta and is analyzing blood samples from the US. We are using antibody array chips to measure over 1,000 proteins in the patient’s plasma for our analytic purposes, and the lab is capable of significant scale-up as needed.

Has OncoHost been validated and its scientific principles peer-reviewed?

We have many peer-reviewed publications on host response, host response mechanisms and host response in different modalities. We will publish the initial clinical results of our platform in lung cancer and melanoma at the AACR and ASCO meetings this year.

What does the future look like for host response profiling and how does OncoHost fit into that? 

OncoHost is the host response profiling company. I believe that in the future we will see more companies that are adding host response into the equation. Looking ahead, I think that we will see an approach that will combine genetic profiling of the tumor and the patient, combined with RNA and protein analysis before and during treatment to predict and monitor the patient’s response, and adjust treatment as seen to be necessary by the patient’s own profile – the host response.

For more on the latest developments in cancer research, visit our feature page >>