Stem cell therapy is one of the most exciting areas of development stage healthcare right now, and it’s being put to the test in a wide range of potential therapeutic areas. Some of these already have relatively effective treatment options available, and the companies targeting them aim to improve on the current SOC and capture market share that way. Others are targeting unmet needs, and looking to bring a stem cell therapy to market that fills a gap in the current system. One of these latter areas of focus is chronic limb ischemia (CLI). CLI occurs when a limb is deprived of blood flow to such a degree that it develops gangrenous ulcers. These ulcers then turn into wounds, and don’t heal properly. There’s no real effective treatment available, apart from antibiotics to stop the wounds becoming too badly infected, and it generally results in amputation. In the US every year, CLI translates to major amputation (an above or below knee amputation, for example) in more than 70,000 US individuals each year. It translates to minor amputation (toes removed, for example) in more than 130,000 US individuals each year.
Stem cell therapy treatment might have an answer to this unmet need, and two companies are pioneering their own individual products in the indication – Pluristem Therapeutics Inc. (NASDAQ:PSTI) and Cesca Therapeutics Inc (NASDAQ:KOOL). Here’s a look at how their respective products work, and where they are from a development perspective.
First, Pluristem.
Pluristem uses a type of stem cell called PLacental eXpanded (PLX) cells. As the name suggests, they are harvested from the placenta, and this gives them a distinct advantage over other types of stem cell – specifically, they don’t need to undergo what’s called HLA-matching before administration. HLA matching is the process through which physicians match patinents with donors for bone marrow transplants. HLA markers are found on pretty much every cell in our body, and they are what our immune system uses to recognize host cells and foreign cells. Normally, if a non-HLA match cell enters the body, the immune system will attack it and the transplant will fail. With PLX cells, however, their low immunogenicity means they don’t alert the immune system to their foreign nature.
With specific relation to the CLI treatment, the company’s candidate is called PLX-PAD. It’s an injection administration of PLX cells, and when introduced, the cells secrete proteins that stimulate the growth of new blood vessels. These blood vessels allow blood to bypass the fat-blocked vessels that are the root cause of CLI, and make its way to the extremities efficiently.
To date we’ve seen two phase I trials – one in Europe (Germany) and one in the US. Both established safety and tolerability, and the company is poised to kick off a pivotal that will span both regions as part of one, multicenter trial, and then use the data from this trial to form the basis of a marketing authorization application for both the FDA and the EMA. The FDA just authorized the trial, and Pluristem expects the same from the EMA at some point during Q4.
The trial is going to be the major driver behind Pluristem’s valuation across the next twelve months.
Moving on, let’s look at Cesca Therapeutics Inc (NASDAQ:KOOL).
This one is different to Pluristem. While Pluristem has developed a direct treatment for CLI, Cesca has created a kit that includes all of the components required for stem cell therapy to treat the condition. It’s kit, called SurgWerks kit, contains harvesting and anticoagulant systems, a cell processing system, a cell delivery balloon catheter and analytic reagents (designed for rapid cell testing). The idea is that the company will sell them directly to hospitals, and physicians undertaking bone marrow transplants will use the kit in the operating room to perform the surgery.
Because this isn’t a drug, the company doesn’t have to put together an NDA for its approval. Instead, Cesca needs to apply for what’s called an Investigational Device Exemption (IDE). It still has to perform rounds of clinical tests to form the basis of the application, and the company is about to carry the kit into a pivotal trial. The endpoint of the pivotal just changed from amputation free survival (AFS) to what’s called Change in Transcutaneous Oxygen Pressure (TcPO2), which markets think will be easier to demonstrate (and in turn, are scooping up stock in the company at time of writing). There’s still a couple of hurdles, however, most notably, the proving that TcPO2 is surrogate to AFS in this indication. That might take a couple of months, or it might take much longer and Cesca is in discussions with the FDA to try and figure out the best way of getting this proof.
Near term milestones on this one are the just mentioned surrogate proof, and the follow on initiation of the pivotal trial. Beyond that, we’re looking for positive outcome data to support an IDE in the US and, eventually, marketing approval.