Patients with sudden strokes and blood clotting conditions need faster and safer treatments. The Dutch company TargED Biopharmaceuticals has raised a €39M Series A round to fund the development of a fast-acting protein drug that could bridge this gap.
Time is of the essence when treating acute ischemic stroke, a condition caused by a blood clot blocking a brain artery. If blood doesn’t reach the brain within several hours, severe disability or death can result.
The most common strategy for restoring blood flow in acute ischemic stroke is removing the clot. Current drugs used to achieve this include alteplase, a protein drug that mimics the action of a clot-busting enzyme that breaks down the key clotting protein fibrin.
“This treatment has been available for a very long time and has done tremendous work in the treatment of acute ischemic stroke patients,” said Kristof Vercruysse, CEO of the Dutch startup TargED Biopharmaceuticals. However, up to two thirds of cases still result in death or permanent disability. Additionally, this treatment risks hitting fibrin outside of the target clot, causing bleeds as a side effect.
Improving acute ischemic stroke treatment is one of the goals of TargED, which raised a €39M Series A round this week. The round was backed by international investors including Andera Partners, Fund+, and Hadean Ventures. The proceeds will support the preclinical development of TargED’s lead protein drug Microlyse, with the aim of entering phase I in late 2024.
Microlyse is a fusion protein drug combining an antibody fragment with a fragment of a clot-busting enzyme. The antibody part of the drug seeks out a protein target found in clots called von Willebrand factor. The enzyme then triggers the breakdown of the clot.
According to recent results in mice, Microlyse cleared small blood clots seven times faster than caplacizumab, an approved anti-thrombotic antibody drug that targets von Willebrand factor. Caplacizumab was developed by the Belgian firm Ablynx, which was acquired by Sanofi in 2018.
“Microlyse is acting very fast, within several minutes, in degrading blood clots and restoring blood flow to bring oxygenated blood back to the distal tissue,” said Vercruysse.
If the results translate to human patients, Microlyse could let physicians treat stroke patients faster than before, raising their chances of recovery. By selectively targeting its clot-busting action to sites with von Willebrand factor, Microlyse could also cause fewer bleeds than current stroke treatments.
In addition to acute ischemic stroke, TargED has its crosshairs on acquired thrombotic thrombocytopenia purpura (aTTP), a rare autoimmune disorder where the immune system destroys a protein essential for preventing clots. This leads to widespread clots that cause organ damage and kill 90% of untreated patients. One common treatment is plasma exchange therapy, where the patient’s blood is cleaned of rogue immune cells and infused with essential clot-busting proteins.
“Microlyse can play a very important role in the emergency setting when patients arrive at the emergency department of the hospital,” said Vercruysse. “It takes between six and 24 hours to set up the plasma exchange therapy. … Microlyse with its rapid mode of action has the capability of restoring platelet counts, rapidly decreasing the need of plasma exchange therapy or even not starting this expensive therapy.”
TargED’s fusion protein technology began its life with an academic group at the University Medical Center Utrecht. As TargED was being set up, the team recruited Vercruysse — who worked on caplacizumab at Ablynx — to take the helm. Shortly after TargED’s founding in 2020, the firm raised a €1.35M seed round. Once its manufacturing was advanced enough, TargED attracted larger investors in this week’s €39M fundraising.
“I believe that there is a renewed interest to invest in the field of acute cardiovascular indications,” Vercruysse told me. “Due to new regulations, alternative approaches, and interest from physicians to clinically trial better treatments in this space, it opens the opportunity for companies such as TargED and others to develop compounds that in the end will save the lives of patients.”
This week also saw positive phase Ib/II results for an antibody treatment for acute ischemic stroke, developed by the French firm Acticor Biotech. Acticor’s antibody targets a protein called platelet glycoprotein VI and is designed to avoid bleeds as a side effect.
TargED isn’t the only company working on fusion protein stroke treatments. Rubicon Biotechnology in the US is working on its own candidate that combines an antibody fragment with a protein that protects cells from damage, called a heat shock protein. The drug is designed to safeguard tissue in situations of injuries and stroke.
“Where Rubicon is developing a fusion protein to have an influence on the viability of cells and apoptosis, TargED is aiming its treatment towards the primary reason, which is the blood clot,” said Vercruysse. “By rapidly acting and degrading the blood clot, we believe that restoring the blood flow is very important. ‘Time is tissue.’“
Cover image via Elena Resko
23 February 2022: article updated to include mention of Acticor’s trial results.