Portfolio Company Spotlight: Alleviant Medical (Chronic Heart Failure)

/ EXPERT INSIGHTS

Portfolio Company Spotlight: Alleviant Medical

ALLAY-HF PIVOTAL TRIAL IN PROGRESS

In US, Canada, Europe, Australia & New Zealand

(February 2025)

Heart failure (HF) is a rapidly growing public health issue with an estimated prevalence of 64 million people globally. The lifetime risk of HF has increased to 24%; approximately 1 in 4 persons is expected to develop HF in their lifetime.

Despite progress in treatment options, there is no cure for HF; it is a serious and burdensome condition often accompanied by a multitude of symptoms, from an irregular heartbeat to fatigue, shortness of breath, nausea, difficulty concentrating, and swollen feet and ankles. Left untreated, HF can lead to liver and kidney damage, as well as other heart conditions, including sudden cardiac arrest.

Many people with HF are able to manage their symptoms and slow the condition’s progression with lifestyle modifications and medicines. Many others remain symptomatic despite guideline-directed medical therapy (#GDMT).

In this Expert Insight, RiverVest Venture Partners highlights a novel investigational medical device designed to address the unmet needs of those HF patients for whom other treatment options have been ineffective. The device is currently in clinical trials for a large portion of these patients and soon to expand investigation to the full spectrum of chronic HF. We are hopeful this technology can deliver the relief these patients so desperately seek.

RiverVest portfolio company Alleviant Medical is investigating a minimally invasive technology (The Alleviant System*) designed to relieve excess pressure buildup within the heart by creating a connection between the left and right atrial chambers through a one-time procedure that leaves no permanent implant behind. This no-implant approach has several clinical advantages over other surgical or permanent implant interventions and preserves options for additional trans-septal procedures that patients may require in the future.

* The Alleviant System is an Investigational Device and is limited by federal (or U.S.) law to investigational use. Exclusively for clinical investigation.

Delivered via catheter, the Alleviant System uses a short pulse of energy for the controlled creation of an interatrial shunt to relieve pressure in the heart’s left atrium.

Last month, Alleviant announced three crucial milestone achievements:

1. The FDA granted the company investigational device exemption (IDE) approval to begin a second pivotal trial, in a

different HF patient population (see below).

2. The FDA also designated the technology with breakthrough status for this patient population.

3. The company raised $90M in a new financing round to fund the new pivotal trial.

With this news, Alleviant’s pivotal trial program is expanding to include patients with both major forms of heart failure — reduced (HFrEF) and preserved (HFpEF) ejection fraction. In patients with HFrEF, the heart muscle is weakened and cannot pump blood as effectively as it should. In patients with HFpEF, the heart’s ability to fill or eject blood (rather than its ability to contract) is impaired.

Pursuing FDA approval across the broad spectrum of heart failure

Pilot studies conducted between 2020-2022 investigated the safety and feasibility of Alleviant’s novel device and examined its mechanistic and early clinical effects. Investigators evaluated a range of factors, including whether the pressure in the left atrium had dropped—a key indicator of efficacy and potential driver of symptom relief—as well as different biomarkers and the patients’ own self-reported symptoms and feelings.

James Udelson, M.D., Chief of Cardiology and Interim Chief Physician Executive of the CardioVascular Center at Tufts Medical Center and Professor of Medicine and Radiology at Tufts University School of Medicine in Boston, observed the prospective, open-label, uncontrolled nonrandomized studies and published his findings in the JACC-HF Journals. The results showed Alleviant’s no-implant interatrial shunt exhibited stability with favorable safety and early efficacy signals.

ALLAY-HF TRIAL

(in progress, on track)

The company’s current pivotal trial (#ALLAY-HF) builds on those positive feasibility results and more than a decade of interatrial shunt study more broadly, incorporating the latest clinical learnings from other pivotal trials to help identify the best candidates for the therapy. Dr. Udelson is the global principal investigator of the ALLAY-HF study, and Matthew Price, MD, Professor of Medicine and Director, Cardiac Catheterization lab at Scripps Clinic, is co-principal investigator.

The ALLAY-HF participants are chronic heart failure patients with HFpEF with EF ≥ 40% who remain symptomatic despite GDMT. The study, which is evaluating safety and efficacy in this patient population, is on track to finalize enrollment within the next year (www.allayhf.com).

ALLAY-HFrEF TRIAL

(new, initiating in 2025)

The new trial (#ALLAY-HFrEF) will continue to build on the positive results of these and other earlier studies, this time evaluating safety and efficacy in HF patients with reduced left ventricular ejection fraction (LVEF ≤ 40%) who remain symptomatic despite GDMT.

ALLAY-HFrEF will be co-led by global principal investigators Dr. Udelson and Gregg Stone, M.D., Director of Academic Affairs and Professor of Medicine and Professor of Population Health Sciences and Policy at the Icahn School of Medicine at Mount Sinai in New York. The study will have an adaptive design and will begin enrolling approximately 350 randomized patients at select sites globally in early 2025.

RiverVest is proud to support Alleviant in its mission to develop minimally invasive therapies to treat heart failure, collaborating with the top leaders in cardiovascular medicine to advance patient care. We are confident the company is in the best of hands with CEO Adam Berman and CFO Mary Byron.

About Alleviant Medical, Inc.

Alleviant Medical, Inc. is a privately held medical device company developing minimally invasive therapies to treat heart failure, collaborating with the top leaders in cardiovascular medicine to advance patient care. The Alleviant System has been granted U.S. FDA Breakthrough Device designation for both major forms of heart failure. The company is headquartered in Austin, Texas, and is backed by leading institutional and strategic investors.

About RiverVest

RiverVest Venture Partners is a leading venture capital firm building life science companies to address significant unmet needs of patients and deliver consistently strong returns to investors. With headquarters in St. Louis and offices in San Diego and Cleveland, RiverVest accesses forward-thinking research and clinical expertise at leading institutions across the country to found and fund biopharma and medical device companies.