ECHO Spotlight Series: NorthMiRs and the Challenge of Sepsis-Induced Cardiac Dysfunction

Entrepreneurship for Cardiovascular Health Opportunities (ECHO) is a 12-month national training program supporting cardiovascular research commercialization through education, mentorship, networking, and funding. Led by a diverse team of experts, ECHO fosters successful startups in cardiovascular health, culminating in an annual pitch competition (ECHO PITCH) offering up to $250,000 in funding.

With the upcoming 2023-2024 ECHO cohort preparing to pitch this fall, we took the opportunity to sit down with some of the ventures involved in the program to learn more about them, their commercialization process, and how the ECHO program has helped them on their entrepreneurship journey so far. First up, we spoke with Samantha McWhirter, Amin Ektesabi, and Chirag Vaswani at NorthMiRs. Samantha McWhirter is the CEO and a Co-Founder of NorthMiRs and is currently completing her PhD in Chemistry at the University of Toronto. Amin Ektesabi is a Co-Founder of NorthMiRs and recently completed his PhD in Medical Clinical Sciences at the University of Toronto, and Chirag Vaswani is a Co-Founder of NorthMiRs and is currently completing his PhD in Physiology at the University of Toronto.

NorthMiRs is developing RNA-based therapeutics that can change the way that physicians, nurses, and medical institutions treat patients suffering from sepsis and related conditions. NorthMiR’s leading product, NM-001, treats sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction is a condition where the heart’s function is impaired due to a severe and widespread infection in the body. When a patient has sepsis, their immune system reacts strongly, releasing signaling chemicals into the blood to combat the infection. These chemicals are intended to treat the infection, but when produced in excess they can cause damage. NorthMiRs’ therapeutics help improve patient outcomes, free up space in the ICU, and reduce the financial burden on the health system.

What was the inspiration behind creating NorthMiRs?

Samantha McWhirter (SM): Sepsis is one of modern medicine’s most urgent crises. It is a life-threatening condition that develops as the immune system responds to any infection in an overwhelming manner, leading to multiple organ failure and ultimately death. It’s not only the most common cause of death among critically ill patients—accounting for about one-third of all hospital deaths—but also a significant financial burden, with the U.S. alone spending over $38 billion on sepsis care in 2017. Despite its prevalence and impact, the last significant medical breakthrough in sepsis treatment dates back to 1918 with the discovery of penicillin by Sir Alexander Fleming. Since then, progress has been notably stagnant, with current care being mostly supportive.

Driven by a desire to find better treatment options for her patients, NorthMiRs’ scientific lead Dr. Claudia dos Santos has spent years exploring novel treatments in the cell therapy space. However, recognizing the limitations and complexities associated with cell-based therapies, she pivoted towards a cell-free approach, setting the stage for an innovative leap forward. NorthMiRs began within the academic laboratories of Dr. dos Santos and Professor Gilbert Walker. This work showed remarkable success in initial in vivo trials. Encouraged by these promising results, the need to translate this academic success into a practical, clinical solution became apparent. NorthMiRs was spun out with a clear mission: to fast track this novel sepsis treatment from the laboratory to the clinic.

Can you explain how the miRNA technology used by NorthMiRs works for patients with cardiovascular disease?

Amin Ektesabi (AE): Of all patients who die from sepsis, 70 per cent show some indication of left ventricular dilation and cardiac dysfunction. Therefore, addressing correct cardiac function is an unmet need that we are aiming to solve with our therapeutic. Our lead product, NM-001, is a treatment for septic patients who experience cardiac dysfunction. It works by delivering synthetic microRNA mimics that decrease systemic inflammation and improve cardiac contractility and bacterial clearance. Our pre-clinical data shows that the cardiac function of a septic heart receiving NM-001 is comparable to that of a non-septic heart.  Overall, this treatment will increase survival and improve recovery rates in these patients.

What makes your lead candidate, NM-001, distinct from other treatments currently available for sepsis?

The problem is that in its current state, sepsis care is inadequate. It is very difficult to treat because doctors have three problems to deal with—the initial infection, inflammation all over the body, and organ dysfunction. They can usually treat the initial infection with antibiotics and can address the organ dysfunction with drugs (such as vasopressors and norepinephrine), mechanical ventilation, and fluid resuscitation. Unfortunately, there are no current therapies that address the immune response causing inflammation, which is why the mortality rate for sepsis is still so high. What sets NM-001 apart from current sepsis treatments is that we directly address the genetic dysregulation that causes the uncontrolled immune response of sepsis.

Cell therapies are another promising treatment in development for sepsis, but they are difficult to scale and are not yet approved for clinical use. We have isolated the most efficacious part of these therapies, miRNA, and packaged them into a stable, scalable, and fully synthetic formulation that bypasses many of the challenges of cell therapies.

What are the next steps in the clinical development pathway for NM-001?

Chirag Vaswani (CV): As we advance NM-001, our next major milestone in the clinical development pathway involves rigorous pre-clinical testing using large animal models. It is crucial to validate the efficacy and safety of our novel RNA-based therapeutic in models which are physiologically closer to humans before we transition into human clinical trials. We are also in the process of securing a GMP manufacturing partner to scale up our batches and to obtain a pharmaceutical-grade product. Our team is preparing for an Investigational New Drug (IND) application, aiming for approval to commence a Phase I clinical trial. This initial phase will focus on assessing the safety profile of NM-001 in a small group of sepsis patients with cardiovascular dysfunction who have not responded to the current standard of care.  Phase II trials will follow, designed to rigorously evaluate the therapeutics’ efficacy in patients where current standards of treatment are ineffective.

You’ve been a part of the ECHO program since the fall of 2023. What makes ECHO unique compared to other accelerators/programs available to health entrepreneurs?

CV: ECHO stands out due to its health-centric approach. Unlike broader accelerators, ECHO specializes in navigating the unique landscape of cardiovascular healthcare innovation. The comprehensiveness and quality of the year-long programming is very impressive, and the high caliber of speakers brought in every week has provided us with advice and insights we can trust. It provides invaluable mentorship from industry experts and access to a network of professionals in the medical, regulatory, and entrepreneurial realms.

Moreover, ECHO’s commitment to fostering innovations that are both commercially viable and have a positive impact on patient outcomes aligns perfectly with NorthMiRs’ mission. The program’s resources have been instrumental in refining our regulatory strategies and strengthening our clinical development plans. ECHO encourages a collaborative environment where peers share insights and strategies, which has been invaluable for navigating the complex landscape of healthcare innovation.

What has been the biggest benefit of being part of the ECHO program so far, and what are you looking forward to in the remaining half of the program?

SM: As mentioned, the level of mentorship and advice available from this program is a huge benefit. We have been able to follow up with some speakers to get more specific advice about NorthMiRs, which is an opportunity we greatly appreciate. We are able to draw on the knowledge of these mentors, and learn from their experience in the therapeutics fields, specifically focused on cardiovascular therapeutics. This has allowed us to hone our regulatory pathway, and incorporate strategies to minimize risks that we otherwise wouldn’t have envisioned. We are very much hoping to participate in the upcoming pitch competition, and the opportunity to get even more hands-on coaching for pitching skills and business development will truly benefit our team.

How does NorthMiRs plan to expand or evolve in the next five to ten years?

SM: When it comes to our clinical development, we are looking to submit our clinical trial application to health Canada for NM-001 in mid-2026 so that we can start our Phase I trials in 2027. If all goes well, we are hoping to mark 5-years post-ECHO by starting our Phase II trial for NM-001 in 2029, hopefully extending into U.S. hospitals as well. During this time, we will also be strengthening our pipeline, focusing on our second product, NM-002, which will heal the lungs of septic patients. To do all this work, we must start raising capital. We have started the process of talking to investors to secure a seed round (2-4M) in 2025 and will be pursuing our Series A (5-7M) to fund our clinical trial in 2027. Ultimately, we will be looking for a pharmaceutical strategic partner to carry our products beyond Phase II, as NorthMiRs’ focus is on the pre-clinical and early clinical development of our pipeline products.

ABOUT ECHO

ECHO is a specialized training program led by veteran entrepreneurs and consultants across a variety of sectors. Its mission is to:

• Provide entrepreneurship training, mentorship, partnership, and funding opportunities for innovators of cardiovascular technologies.
• Create more successful start-ups in the cardiovascular health sector.
• Accelerate the application of cardiovascular innovations and their transfer from bench to bedside.

ECHO is funded and organized by the Translational Biology and Engineering Program at the University of Toronto and the Ted Rogers Centre for Heart Research, in partnership with the Health Innovation Hub (H2i). To learn more, please visit https://tedrogersresearch.ca/echo-pitch/