Last year, when Harvard Bioscience (NSDQ:HBIO) spun out its regenerative medicine business as Harvard Apparatus Regenerative Technology (NSDQ:HART), David Green decided to leave the top spot at Harvard Bioscience to lead the HART spinout.
Leaving HBIO after founding and running it for 17 years was a big decision, Green tells MassDevice.com, driven by his belief that we’re poised on the edge of a new age in regenerative medicine.
"It’s nothing short of the transformation of medicine," Green says. "Regenerating organs or tissues for transplant has been a dream for doctors and science-fiction writers for decades now, and it’s finally starting to become reality."
Indeed, it’s been nearly 6 years since the 1st artificially grown trachea was implanted into a Colombian patient.* At the 5-year mark, Claudia Castillo, who received the trachea implant at the age of 30, was "living normally without any complications or rejection of the implanted airway."
When news of the procedure 1st broke, Green picked up the phone to call Italy to get in on the game. Harvard Bioscience eventually launching a commercial version of the bioreactor researchers used to grow the bronchus. So it’s really no surprise that Green elected to shift from HBIO to HART, which in addition to creating artificial tracheas is developing an artificial esophagus. Green tells us that replicating those simple organs using patients’ own cells is just the beginning, predicting that eventually we’ll be able to create more complex organs like the heart or lungs with no risk of rejection.
Below is a transcript of our chat, edited for clarity, in which Green explains the technology behind the artificial trachea, his faith in the promise of regenerative medicine and a forecast for its future:
MassDevice.com: Tell us about the spin-off from Harvard Bioscience last year – what drove that decision?
David Green: HART, which is the regenerative-medicine business, was spun out from the parent company Harvard Bioscience, so now both HART and Harvard Bioscience are independent public companies. There’s no cross-share holding or anything like that. They’re 2 completely independent companies.
The reason we did that is because they’re really 2 very different businesses. The Harvard Bioscience business is a stable, profitable, mature, modest-growth business. It’s very profitable. It’s been around for over 100 years, and it generates a lot of cash flow. There’s a certain group of investors who find that very attractive as an investment.
HART is a biotechnology company that is likely to be losing money for several years and has no revenue at all today, but if our product works, our regenerated organs for transplant, if they work, then this could be a transformation of the way that medicine is practiced, and that could be worth billions of dollars.
They’re really very, very different businesses. One’s really a biotech startup business, and one’s a mature, profitable, cash-flow business. They became increasingly in conflict with each other, and so we decided to spin them off, and we completed that about six months ago.
MassDevice.com: What was attractive about moving with HART, rather than continuing to lead the legacy business?
David Green: Well, that’s a good question because I was the CEO of the legacy business, and in fact, I built that business. I founded it in 1996, and so I did 17 years running that company, so it would have been very easy for me to stay. The reason I jumped ship, if you like, to go and run HART is really twofold.
First, I think the opportunity is huge. As I said, I think it’s nothing short of the transformation of medicine. Regenerating organs or tissues for transplant has been a dream for doctors and science-fiction writers for decades now, and it’s finally starting to become reality. We have 8 patients who’ve been treated with our regenerated tracheas, so it’s finally starting to become a reality.
I really think the upside here is huge, but that is true with most biotech companies. Most biotech companies have a very promising new technology that’s going to allow them to cure some awful condition in patients, so that is quite common in biotechnology. What I think is very uncommon in where we are with HART is the fact that we have human clinical data.
If you have any experience with investing in a biotechnology company, you’ll realize something that I call the "Oscar-night moment," because when you get up there and you’re revealing your clinical trial data for the first time, you’re either the winner or you’re not. There’s usually no sort of halfway position. If you’re the winner, if your product actually works on patients, then your company’s probably worth $1 billion; and if it isn’t, then it’s probably not worth very much at all. You typically don’t get to find out whether the product really works in humans until those very late-stage clinical trials, typically Phase 3 clinical trials.
The beauty of what we’ve done is we have human clinical data before we even start the clinical trials. While that doesn’t guarantee that it’s going to be a success, it certainly greatly increases the odds, and so I think we’ve got this huge upside potential, but, at the same time, we’ve taken the bulk of the risk out of the business at this point. That’s why I thought it was such a compelling opportunity, the huge upside with the bulk of the risk taken out of it.
MassDevice.com: Can you give us just a bit of a primer on the technology and how it’s applied to create a human trachea? Are there other organs it could potentially be applied to?
David Green: The way we make a regenerated trachea for transplant today involves 3 things. First, we have cells. Second, we have scaffold, and 3rd, we have bioreactors.
The cells we use are human cells taken from the patient, so we take a bone marrow biopsy. That means we just take out some of the bone marrow from the patient’s hip bone, and from that, we extract the cells. It’s the iliac crest, which is the hip bone. That’s where the bulk of the bone marrow is, or at least the easily-accessible bone marrow is, and you just take it out with a syringe. It’s a minor procedure. It typically takes 20 to 30 minutes per patient.
The 2nd thing is the scaffold, and the scaffold is made of a porous plastic. It’s made of fibers that are wound up together onto a shaped piece of metal that’s shaped in the size of the patient’s natural trachea. That scaffold is then seeded with the patient’s cells. Seeding the cells means washing the cells over the surface of the scaffold. Because it’s porous, the cells filter through the fabric material, and they stick to the plastic fibers. In fact, this fibrous structure is very reminiscent of the natural bone structure in the iliac crest, so the cells sort of feel at home there. It feels very much like their normal environment.
Then it takes 2 days for the cells to grow and fill out the scaffold. That’s why we use the 3rd component, the bioreactor, which is a specialized cell-seeding and cell-culture device that keeps the scaffold and the cells sterile and warm and fed for the 2 days prior to the surgery.
MassDevice.com: I can’t believe it only takes 2 days. That’s amazing. What’s the next step once the trachea is grown?
David Green: Then the surgeon surgically removes the old trachea. Typically, the old trachea is narrowed, so the patient’s having difficulty breathing. Usually, that’s because there’s a tumor, like a trachea cancer growing in the throat, or because there’s tracheal stenosis, which means a narrowing of the trachea caused by some kind of physical damage. Typically, it starts with a road accident, and that’s what leads to the physical damage of the trachea. One of those 2 things, either physical damage or a trachea cancer, is what causes the patient to need this kind of transplant.
MassDevice.com: When we spoke in March 2010, you said that regenerative technologies will quote "transform the practice of medicine." I take it by your remarks that that’s still your view?
David Green: It’s very much my view. I think we are starting with the trachea, but you asked earlier what other organs do we think we can apply this kind of technology to, and I think you’ll see the next organs in other hollow, tubular organs in the body like the esophagus. The esophagus is a tube that runs down from your mouth to your stomach, where the trachea is the 1 that runs down from your mouth to your lungs, but they’re broadly similar. They’re both fairly long, narrow tubes, and so we think the technology of making these scaffolds, of seeding them with cells, of using the bioreactors to culture them can be used to go into organs like the esophagus.
Recently, 1 of our collaborators, Dr. Paolo Macchiarini, who is the surgeon who did the very first surgery back in 2008, published a paper in Nature on the regeneration and transplant of an esophagus in a rat. It’s never been done in a human, but it has been done in an animal. That’s how the trachea began 5 or 6 years ago, and I think you’ll see a steady progression from the trachea, 1st through other hollow organs like the esophagus to other, more complex organs like the lung.
MassDevice.com: What is it about the tubular organs that lends them to being reproduced in this manner?
David Green: It’s relatively easy to make a scaffold for a tubular organ. That’s really the thing. If you think about what the scaffold for, say, a heart or a lung would look like, it’s much, much more complicated, whereas making a material, a fabric-like material that allows the cells to penetrate but doesn’t let them just wash out, it allows them to stick to the scaffold, as well, and grow and feel like home is very difficult. But it is possible for us to make thin fabrics of that kind of material and to make those fabrics in natural shapes like tubular shapes like the trachea and the esophagus.
It’s much more complicated to build a similar fibrous sort of structure for complex, 3-dimensional organs like the heart, the lung, the liver or the kidneys. That’s why I think those organs will be later. I think it is inevitable that those organs will be regenerated using similar techniques, but I think you’ll see the earlier ones to be done will be these tubular organs like the trachea and the esophagus
MassDevice.com: Does this, because it’s generated from the patient’s own cells, sidestep the potential rejection of the organs by the patient?
David Green: Yes, it does. Of course, the bane of all organ transplants has always been that, yes, you can get a new organ from someone, but your body’s going to reject it, and so to avoid that rejection, you have to take immunosuppressive drugs, drugs that suppress the immune system so that your body does not reject the tissue from the donor.
Because we use the patient’s own stem cells, their bone-marrow cells, you do not get that rejection, and none of the patients who’ve received these trachea transplants have ever taken immunosuppressive drugs. That really is 1 of the critical breakthroughs of this technology is the ability to do an organ transplant without immunosuppression.
The other 1, of course, that is not obvious is we make them in a factory, so unlike having to wait for someone to die in order to get donor organs, we can just make them to demand, so you can have essentially unlimited quantities of organs made this way. Really, this work has really addressed both of these critical constraints to organ transplant: 1, the immune suppression; and 2, the lack of supply of organs from donors.
MassDevice.com: Where are you on the regulatory pathway, either overseas or here in the U.S.?
David Green: We are in discussions with the FDA about beginning clinical trials, and we expect to begin clinical trials next year in the U.S. We’ve had our pre-IND meeting with the FDA. That’s sort of your first official meeting with them, and we would expect to file the IND, which is permission to begin a U.S. clinical trial, next year. In Europe, we’re following a parallel path, and the European pathways are a little more flexible than the U.S. pathways, and so we anticipate we would actually be able to sell the product, not just begin the clinical trials, but sell the product in Europe before the US.
MassDevice.com: Right. What about funding and financing?
David Green: HART was financed with $15 million in cash contributed by the parent company, so that’s our startup capital, if you like.
MassDevice.com: Assuming a positive result from the FDA, will you be looking for further financing to achieve scale here in the U.S.?
David Green: That’s an interesting question. One of the things we have considered is raising capital to fund some of these 2nd programs. The trachea program we are currently funding out of that cash we received. There’s not enough cash there for us to be able to fund multiple programs simultaneously, to fully fund the development of, say, an esophagus, a regenerated esophagus or a regenerated lung.
So regeneration and transplant has been done in the esophagus, and it has been done in lungs, both of them only in rats. They’ve never been done in humans, but to put programs like that into full clinical development would require much more capital than we have, so we definitely have considered raising capital specifically to initiate the clinical development of those other organs.