Targeted Therapeutics for Critical Illnesses: Interview with Jason Springs, CEO of Endpoint Health

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With the COVID-19 pandemic, critical illnesses, such as Acute Respiratory Distress Syndrome and sepsis are coming into the spotlight. Despite their severity and risk for patients, critical illnesses remain understudied and lack the number of treatment options of many other diseases with a similar level of mortality and morbidity.

Part of the challenge lies in the time sensitivity of such conditions, whereby clinicians have little time to make treatment decisions and typically can’t tailor the treatment for individual patient needs. The quest to develop more tailored treatments for such illnesses is what drives Endpoint Health, a company based in Palo Alto, California.

The company aims to use AI and integrated data to identify subgroups of critically ill patients that could benefit from specific therapeutics, which are either existing or repurposed drugs. The idea is to give clinicians a better arsenal of therapies with which to treat critically ill patients and make better treatment decisions, something that would be particularly useful during the current pandemic.

Medgadget had the opportunity to talk to Jason Springs, co-founder and CEO, Endpoint Health about the company and their mission.     

Conn Hastings, Medgadget: Please give us an overview of critical illnesses such as Acute Respiratory Distress Syndrome and sepsis and the burden they pose for patients, clinicians, and society. 

Jason Springs, Endpoint Health: Every year, our children, parents and loved ones develop critical illnesses such as sepsis and ARDS, which affect millions of people, are linked to the majority of hospital deaths, and have costs in the hundreds of billions (USD). In fact, critical illness leads to:

  • 70% of U.S. hospital mortality
  • >$100 billion annual cost to the health care system
  • 99% of COVID-19 mortality (critical COVID-19 patients die from ARDS and sepsis)

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition that results when fluid builds up in a person’s lungs, which then restricts oxygen from reaching the bloodstream, therefore depriving organs of the oxygen they need to function. ARDS is one of the primary causes of death for COVID-19 patients. In addition to COVID-19, causes include vaping, pneumonia and sepsis. 30-40% of those who develop ARDS will die.

Sepsis, a life-threatening immune response to infection, is the poster child for critical illness. Prior to the pandemic, it already had an estimated cost of over $60 billion per year in the U.S. and was linked to more global deaths than cancer per year (11 million vs. 9.6 million).

Clinical researchers know that these illnesses are not single diseases but rather heterogeneous syndromes, that new therapies are needed, and that each treatment choice should be personalized. But despite the urgent nature of critical illnesses, advances in new and personalized care still lag behind other areas of medicine.

Medgadget: What limitations are there in current treatment approaches for such patients? Are such patients underserved?

Jason Springs: Critical illnesses happen suddenly and progress rapidly. For comparison, in the time it takes to return tumor biopsy results, a critical care physician may make dozens of treatment decisions for multiple patients, each with life or death implications. Each patient has multiple clinical challenges that must be overcome simultaneously: They need oxygen, dialysis, they often need to have balance restored to both their immune system and coagulation functions. Each choice and moment leads to changes in the patient. Critical illnesses are like speed chess, where every minute counts, the challenges are dynamic, and the permutations of choice can be more than a human mind can fully grasp. This speed and complexity challenge has led to two main challenges in caring for critically ill patients:

  1. Understanding which patients may respond to existing therapies on a personalized level is incredibly difficult for clinicians – thus leading to more generalized treatment protocols.  
  2. No therapies are approved for the underlying immune dysregulation that causes sepsis or ARDS. The hypothesis behind this was that previous attempts to approve therapies for sepsis patients could not target the correct patients (the ones that would respond positively to the therapy). Targeting patients likely to respond to a therapy was incredibly difficult or impossible in the past given the complexity of the patients and the short time-frames for decision making.  

The result is a group of patients that are dramatically underserved compared to other disease areas. For comparison, while sepsis is associated with more global deaths each year than cancer, there are no approved therapies. In cancer, there are more than 580 approved therapies.

Medgadget: Has the COVID-19 pandemic changed how such patients are treated? 

Jason Springs: The COVID-19 pandemic, which placed unprecedented numbers of patients in the ICU, has drawn the world’s attention to the desperate need for advances in the field of critical illness. This has led to a large increase in investigating the use of existing and novel therapies to improve survival of critically ill patients. In particular, a wide range of anti-inflammatory therapies and immuno-oncology therapies are being tested in COVID-19 induced ARDS and sepsis patients.

Medgadget: Please give us an overview of Endpoint Health, and your mission.

Jason Springs: Endpoint Health was founded in 2018 by an experienced executive team including the co-founders of GeneWEAVE, an infection detection and therapy guidance company that was acquired by Roche in a 2015 deal valued at $425 million. The company launched with a mission to bring life-saving targeted therapies to patients with critical illnesses such as sepsis, ARDS and COVID-19. Endpoint Health is building the world’s first precision medicine ecosystem focused on critical illnesses such as sepsis and ARDS, and is using it to unlock a deeper understanding of patient biology, to see how this biology impacts treatment response, and to develop new targeted therapies as well as validate targeted methods of delivering existing care.

The company is based in Palo Alto, Calif., with offices in Detroit and Chicago, and is backed by top-tier investors including Mayfield, Y Combinator, AME Cloud Ventures, and Wireframe Ventures.

Medgadget: How will Endpoint Health develop targeted treatments for such patients? Please give us a summary of how integrated data and artificial intelligence will assist in this process.

Jason Springs: We use AI techniques to analyze digital (EHR) and molecular data (RNA, proteins, etc.) from critically ill patients to deeply understand their biology, how distinct subgroups of patients may respond to various novel and routine therapies, and to design blood tests and electronic algorithms that could rapidly identify these subgroups and thus potentially be used by physicians as companion diagnostics to target new therapies as well as routine care choices. Our process then is to identify pharma companies that own rights to new therapies our research process has identified as having high-potential to improve patient outcomes. These therapies are often in clinical-development for other applications outside of critical illness. We then enter in-licensing or co-development partnerships and use our companion diagnostic products in clinical trials to target the candidate therapies to critically ill patients that are likely to respond positively. Then, if the trials are successful, the companion diagnostics and therapies would both be approved for use as an integrated product – a “targeted therapy” for sepsis or ARDS for example. The goal is to bring multiple targeted therapies to market and to personalize how current routine care is delivered for critically ill patients.

Link: Endpoint Health…





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