Like whole blood for transplants, platelets are perpetually in short supply. But these sticky cell fragments come with an added challenge—while whole blood can be kept for as long as 35 days after donation, platelets generally must be used within five days.
“Because of the short shelf life, you can’t bank platelets—so even if you get a ton of donations, you can’t keep them,” Ashley Brown, Ph.D., a biomedical engineer at North Carolina State University (NCSU), told Fierce Biotech Research in an interview. On top of that, “transporting them can also be problematic.”
“It’s not typically standard to have platelets or other blood products in an ambulance or to transport them to remote locations such as rural hospitals and battlefield situations,” Brown said. “These are all areas where it’s very common to have bleeding problems, but it’s really hard to get platelets there.”
Now, her team at NCSU has come up with a possible solution: synthetic platelets. In a new report published April 10 in Science Translational Medicine, the researchers demonstrated that they work in mice, rats and pigs—studies that will likely be part of an investigational new drug application with the FDA under SelSym Biotech, a company Brown co-founded with three fellow authors of the paper to commercialize their work.
“We wanted to create a product with a long shelf-life that can be produced in mass quantities and be transported to these remote locations,” Brown said. “Those were the design criteria we had from the outset.”
Building with biomaterials
While some have attempted to solve the shortage by upping donor platelets' shelf-life, these efforts so far have stretched it to just a week. Unlike whole blood or red blood cells, platelets are required to be stored at room temperature, as refrigeration is considered to degrade their function and compromise their survival once they’re transfused into patients. And, while at least one clinical trial has shown that this isn’t necessarily always the case, for now, the room temperature standard remains in place. It means that platelets are stored in conditions ripe for bacterial growth, which is one of the reasons they must be used soon after they're donated.
SelSym’s solution involves what Brown described as a “biomaterials approach.” Their product is tiny bits of ultra-soft hydrogel outfitted with antibodies that bind directly to fibrin, a protein that’s found at the site of wounds. These “platelet-like particles”— or PLPs, as Brown’s team called them in the new paper—circulate through the body until they come into contact with fibrin, which sets off a chain of processes that stops the bleeding.
“This way, we can make something that is scalable and could be easily made at quantities that will allow for it to be produced for translatable purposes in the future,” Brown explained. Hydrogels can be readily manufactured in large volumes, and the company is in the process of finding out whether the fibrin antibody the product requires will be scalable, too.
SelSym’s strategy is different from that of another player in the synthetic platelet game, Haima Therapeutics. First, SelSym’s product is designed to mimic only one aspect of platelets’ many different roles in bleeding control—in this case, what’s known as secondary hemostasis, where platelets bind to fibrin. In contrast, Haima’s product, SynthoPlate, augments some components of primary hemostasis as well. Second, SynthoPlate is a nanoparticle built from a liposome covered in peptides, a slightly different approach from the antibody-coated hydrogel built by SelSym.
Brown’s team decided to target fibrin alone for a couple reasons. For one, doing so reduces the risk of off-target blood clot formation, an inherent concern with any product to stop bleeding, she noted. And the PLPs’ soft, squishy design has the bonus benefit of promoting better healing by enhancing what’s known as clot retraction, a process where the clot becomes smaller as it drains out excess fluid. Her team has already explored this quality in other studies.
“We've been really focused on this clot retraction aspect of our technology and on how it can enhance healing,” Brown said.
Multiple models
The experiments in the new article tested the PLPs’ efficacy against trauma-induced bleeding in mice, rats and pigs. In all cases, the particles worked as well if not better than natural platelets at stopping bleeding, study data showed.
The side effect profile also appeared promising, with no adverse effects or off-target blood clots. The only blood changes the researchers saw that couldn’t be explained by the trauma modeling procedure or subsequent treatment were transient declines in the particle-treated pigs’ white blood cell levels, which resolved within a week, the study said. There were no traces of the PLPs in any of the animals a week after the procedures, a sign they’d been excreted completely via the kidneys.
“We demonstrate here that [the PLPs] do not have major systemic risks and have an advantageous method of clearance, suggesting tremendous translational potential,” the scientists wrote in the article.
Of course, just because a drug is well tolerated in animals doesn’t mean the same will be true in humans. Early studies on how the particles interact with immune cells didn’t raise any red flags, and the researchers selected materials that have a low chance of sparking an immune reaction, Brown said. The results in pigs are particularly hopeful, as none of them developed a major porcine-specific immune reaction that sometimes occurs in response to nanoparticles.
Still, “we haven’t done a really extensive analysis of immune reactions,” Brown noted. “Everything we’ve seen so far points to the particles being well tolerated once we get to human studies, but it’s important to note that we haven’t tested them in humans yet.”
Those studies are likely a couple years out. SelSym is in the process of planning additional preclinical research projects that will be submitted as part of its IND.
“These things are always tricky [to predict], especially for a product like this,” Brown said. “We’re hoping that, definitely within two years, we’ll be in clinical trials.”
Moving forward
SelSym has received about $3 million in grants from the National Institutes of Health since it was founded in 2019, according to Brown. The money so far has gone to preclinical research and to studies on manufacturing feasibility. To support an IND milestone, the company has launched a seed round to raise $5 million, which will be followed by a $20 million series A.
“That would get us through our next major inflection point, which is a phase 1 clinical trial,” Brown said.
The biotech is open to partnering with larger companies as well as to collaborating with other upstarts that are working on similar technology, like Haima. Brown’s lab at NCSU already has an ongoing partnership with the lab of one of Haima’s co-founders, Anirban Sen Gupta, Ph.D., to see how future generations of their synthetic platelets could be combined. That work is currently being funded by a new four-year, $2.75 million grant from the Department of Defense.
“On the academic side, we’re figuring out how to combine these types of technologies to get a little more bang for your buck,” Brown said.
While there’s much more work to be done, the findings from the latest study are a sign that SelSym is moving in the right direction.
“I know it may sound a little cheesy, but the whole reason that we started this work in the first place was to try and impact clinical outcomes for this really big problem,” Brown said.
“We’re really hopeful that we can take what we’ve learned in these animal studies and translate it to preventing deaths that shouldn’t happen.”
Editor's note: This article has been updated to clarify that SelSym is raising a $5 million seed round before launching a $20 million series A.