EpiBone

Homegrown Replacement Parts

Andrew Kuzemczak
February 18, 2025

Hi,

I hope you all enjoyed your long Presidents' Day weekend! For those on the east coast, I nearly got whiplash from how quickly that blizzard became a rain storm. Stay warm (and dry) out there!

Welcome back to Future Human! I hope you all don't mind the A/B testing on our newsletter release times. I was pretty set on 8 AM but wanted to briefly see how our open rate changes with a 1PM release. We're building the ship as we sail it, so I hope you understand. I schedule my LinkedIn posts daily for 8AM, so I'm not sure if it is more valuable to diversify the content times or keep it all the same. Tune in next week for the update!

Last week’s first release was amazing! Thank you all for the support. It will be hard to beat with a 75%+ open rate! The feedback was so sweet and we even got two sponsor offers (although I will be holding off until we are a bit bigger before adding ads, don’t worry). I am even more excited this week to write, so let’s dive in.

Here at Weill Cornell we are deep in pulmonology (that’s the lungs - for our finance friends). As I brainstormed this newsletter edition a couple weeks ago, I considered keeping the topics aligned with my medical curriculum just for fun. Then I realized in two weeks we start the GI unit and I'm not looking to write about intestinal innovation for two newsletters, at least not yet. So with regards to our Ferrari, we are going to skip the lungs (air intakes? cabin filters?) for now and jump to a ridiculous startup that I have been following for three years. This founder was the commencement speaker at my Columbia graduation, so consider this a bit of newsletter nepotism.

What are the orthopedic equivalents in our Ferrari? Bones and joints become…perhaps wheels, shocks, axles, and bearings. These are key parts for the vehicle’s drivability. Now imagine you have an issue with such parts, hindering your vehicle’s ability to move. The question is then quite simple:

When replacing parts on your Ferrari, would you pay for them direct from Ferrari (Original Equipment Manufacturer - OEM) or accept risks to save money with aftermarket suppliers?

The Story

The human body’s equivalent for OEM would probably be our stem cells — the most original cells we can get. These are the unspecialized cells we all have which differentiate overtime to become the specific tissues of our body. Countless teams, universities, and companies have now taken on the mission of figuring out how to guide the cells to create tissues we need in predictable ways. This is no different for Nina Tandon and her team at EpiBone.

Nina completed her PhD in Biomedical Engineering at Columbia in 2009. She had become obsessed with the brain-computer interface and its ability to manipulate electricity to solve blindness. That was until she paid a visit to Robert Langer’s lab at MIT.

Dr. Bob Langer is the world famous inventor, engineer, founder, and Institute Professor at the Massachusetts Institute of Technology. He is the scientist behind Moderna’s technology and ‘godfather’ of tissue engineering.

In the Langer Lab, Nina realized the electricity she was interested in, mixed with some chemistry, could be used to create a ‘bioreactor’. These bioreactors tricked cells into thinking they were in the body and growing like they would normally. Then she wondered with Dr. Langer and her soon to be co-founder Sarindr "Ik" Bhumiratana, where can this be best applied?

They agreed that humans are living longer and getting injured earlier. Consider that ACL tears for girls under 18 has risen 400% in just the previous decade. If we are tearing an ACL at 15, but now living until 115, surely the replacement parts must be able to keep up. Unfortunately, they weren’t.

Together, Nina and her team cofounded EpiBone in 2013. EpiBone has been on a mission to use patient stem cells to grow bone and cartilage tissue to fit the individual’s needs.

EpiBone product examples (personalized bone and cartilage)

The Tech

Some rapid-fire science and medicine for your Tuesday afternoon. The current gold standard for bone repair is autograft. Autograft is a tissue transplant where the donor and recipient are the same person. With bone autografts, we cut pieces of bone from your hip, rib, or tibia and insert them at the injury site with the goal being full integration. For cartilage, the options aren’t as well defined, so many are trying to develop artificial gels to replace injured or missing sections.

EpiBone goes one step up the cell lineage to begin their product development. By harvesting stem cells from the patient in need, they can create tissue (bone, cartilage, or a compound of both) that fits each specific patient (in shape and genetics).

EpiBone bioreactor

The technology at the heart of EpiBone is the bioreactor. This machine mimics the calibrated conditions in the human body that enable bone (or cartilage) to grow. The proprietary bioreactor is the product of 20 years of research and experience with orthopedic tissue engineering in the Langer Lab. The tech has become so good that they can restrict the development of any unwanted cell lines or tissue types aside from the bone or cartilage needed even when beginning with completely undifferentiated stem cells.

The EpiBone bone process comes in three steps (cartilage development less involved):

Imagine & Stem Cell Extraction: use a CT scan to determine the exact 3D size and shape of the bone a patient needs. At the same time, extract adult stem cells from the patient’s abdominal fat.
Graft & Bioreactor Design: create a precise, personalized model (or “scaffold”) of the needed bone. Design and build a custom bioreactor that will incubate the new bone as it grows. Meanwhile, nourish the stem cells such that they multiply and start becoming bone cells.
Bone Growth: all the ingredients come together. Infuse the stem cells into the scaffold and grow them inside the bioreactor. The cells remodel into a personalized bone graft ready for implantation.

EpiBone pipeline

EpiBone is currently working on three products: bone, cartilage, or a combination of the two. The status and timeline of each is as follows:

EB-CMF - bone
- Timeline: 3 weeks to engineer bone
- Status: Phase I/IIa competed Aug 2023
EB-OC - osteocondral (bone and cartilage) combination
- Status: IND approved July 2023
EB-IAC - cartilage
- Timeline: 4 weeks to engineer cartilage
- Status: beginning IND-enabling study
- Notes: aim to create injectable, fully funded by DoD so far

Late last year, EpiBone announced an $18.5M Series B. This funding will be used to push EB-CMF (bone) to Ph III IND approval, EB-OC (bone/cartilage combination) to PhI/II with 12 patients, and EB-IAC (cartilage) to its first IND-enabling studies.

This collision of personalized medicine and orthopedics is truly groundbreaking. I got chills on many occasions in doing all this research. To be able to order a perfect part, in shape and genetics, for your body is something truly sci-fi that may no longer be. That capability, placed within the massive orthopedic repair market, is something most Fortune 500 CEO’s dream of.

Speaking of the orthopedic repair market, let’s pay it a visit.

The Market

Bone is the most transplanted tissue after blood. I’m not sure about you, but that surprised me. I don’t know what I expected to be second, but it wasn’t bone.

Over 2M orthopedic procedures involve bone grafting annually around the world. 500K of those occur in the US. Whether you are involved in medicine directly or not, you are well exposed to the prevalence of bone and joint problems across the country and the globe. The patient population is growing with no signs of slowing down.

Consider these drivers:

Osteoarthritis: increasing prevalence (degenerative joint disease causing cartilage wear)
Sports injuries: rising number of sports participants across all ages (think grandma crushing it in Pickleball)
Obesity: increasing BMI places heavy burden on bones and joints
Elderly population: rapidly accelerating geriatric category worldwide

So how do orthopedics stack financially? Well across EpiBone’s areas of interest, we find bone fracture repair globally bringing in $16.8B in 2024 and growing to $24.9 billion by 2031, at a CAGR of 5.8%. Cartilage related repairs represent a smaller $5.5B market globally. Joint replacement (requiring bone and cartilage), however, takes the cake as a $20.3B market growing to $32.2 billion by 2035.

Just as an example, among American adults, 32.5M suffer from osteoarthritis. There is no cure (see above, we are also living longer and getting injured younger), so repairs must keep up. The market will continue to rage, and investors have taken notice.

Some of the biggest successes in health tech are in orthopedics. Nina and her team are well aware of this. In reviewing their pitch/funding documents, I noted EpiBone already made it clear to investors that these incumbents have plenty of capital to make an acquisition offer as the team’s tech shows more promise.

They have specifically labeled the below powerhouses:

Arthrex (privately held orthopedics company specializing in laparoscopic repair)
- $3.2 billion revenue (2023)
Stryker
- $20 billion revenue (2023)
- 40% of revenue coming from orthopedic division
Zimmer Biomet
- $7.4 billion revenue (2023)
Medtronic
- $31 billion revenue (2023)
- Orthopedic specialty: cranial and spinal repair

With Series B funding now in hand, however, it will be interesting to see if EpiBone continues to pursue such partners as aggressively.

The Sick

Orthopedic repair operations historically have high success rates, but ‘success’ and patient satisfaction are two very different concepts.

From the physician’s perspective, only 2-5% of joint replacement surgeries come with complications. Some of these complications, such as heart attacks, strokes, and respiratory issues, result from anesthesia; others, including infections, fractures, implant failure or loosening, and unexplained pain, result from the procedure itself. Although these rates are low, it is critical we look to the patient directly to consider their own personal ‘success’.

Patient dissatisfaction is notoriously much higher, coming in at 20% for a common surgery such as total knee arthroplasty (TKA). Excluding complications, the average rate of dissatisfaction arrives at about 10%.

Here’s a shocking stat — if you are 60+ getting a knee replaced, your median time to revision surgery is under 5 years. How can we offer something and label it successful if it will barely last me through medical school? So, I say again, just because a medical team defines something as successful in the moment or over the coming year, does not mean all are satisfied.

To repair your body with genetically matched and shaped ‘OEM’ parts would be a new gold standard for patients for a variety of reasons. Consider, most obviously, that transplanting anything new with metal alloys and plastics come with risk of rejection or infection. Even in the best case scenario, however, with no rejection, few would argue that installing new metal and plastic is preferred over providing your body its own cells to fix itself.

For the sick, EpiBone also fills a need far beyond the physical. While most bone/joint repair patients welcome the pain relief that comes with a procedure, some experience psychological impacts. In a 2022 paper, researchers discovered knee replacement patients often described their knee as 'alien,' 'foreign,' or 'not part of' themselves. The research team actually shifted plans to then better understand how embodiment (of both having a body and experiencing the world through one's body) and incorporation (integrating something into one's body) might play into the experiences of pain and discomfort after total knee replacement. Ultimately, the team discovered that patients felt but often hesitated to share a lack of connection with and agency over their replaced knee, often describing it as other, and lacked confidence in the knee.

Although I, nor EpiBone, are here to claim that stem cell regeneration will prevent foreignness, it does seem like the best approach possible to avoid such complications.

The Economy

If your Ferrari can’t drive, how are you going to make sure people know you have a Ferrari? Sorry, not that.

How are you going to make sure you get where you need to go? Much better.

The economics of movement are fascinating. Assuming EpiBone will grant patients their mobility back, they are poised to have a massive impact on the global economy.

In a massive 2018 paper looking at health and income relationships across 12.6M patients, the researchers labeled a number of prominent economic drivers. Put simply, they showed that faster walking speeds and mobility are strongly associated with higher income. In more detail, they sampled the patients and found a 550-step-per-day increase in mobility would:

Reduce:
- Functional status limitations by 5.9%
- Total medical expenditures by 0.9%
- Nursing home utilization by 2.8%
Increase:
- Employment by 2.9%
- Earnings by 10.3%
- Monetized quality of life by 3.2%

Keeping people on their feet longer not only improves their mental health (see above, embodiment and integration) but also generates tremendous financial value both for the patient and the economy via employment longevity.

If we just focus on osteoarthritis (OA) for a second (recall, 32.5M Americans suffer from it), we find the impact of improving mobility extends far beyond the return to work mentioned above. It also drastically saves on healthcare costs given that the return to movement reduces rates of comorbidities.

Some facts — 40% of men and 57% of women with knee OA are physically inactive. The CDC reports that 47% of adults with arthritis in the U.S. have one or more other serious health problems. Common associated issues include:

Heart disease, 24%
Chronic respiratory conditions, 19%
Diabetes, 16%
Stroke, 7%

Treating OA with personalized replacement parts could certainly have downstream effects on these other diseases which plaque modern society.

Final facts — bone and joint disorders account for 440 million lost days at work and $110 billion in lost wages each year — more than any other medical condition.

Workers with OA are one-third less productive than non-afflicted workers
Total knee replacement surgery generates net societal savings of approximately $19,000 per patient lifetime due to reduced disability costs and improved productivity
- Procedure cost: $12,000-15,000

Now imagine this impact with reduced risk of complications, rejections, or feelings of foreignness.

My Thoughts

Although ortho is no cardio, it is undeniable that one is intertwined with another. An engine with no wheels is far from useful.

Nina, Sarindr, and the entire EpiBone team are redefining what tissue engineering could mean for millions of patients globally. They are repairing wheels, axles, and bearings with the most original of OEM parts — stem cells. Although the science is remarkably complex, the principles are shockingly simple — heal with your own cells to return to movement sooner.

I have really enjoyed staying up to date on Nina’s work over the last 3 years and will continue to do so moving forward. I am deeply grateful to Columbia for incubating such curiosity and sprouting a startup that could one day save countless lives. I am taking it all in as serious inspiration for my long term plan as a physician, entrepreneur, and Columbia alum.

If you want to learn more about EpiBone, check out their website or reach out to Nina Tandon on LinkedIn!

To more lives saved,

Andrew

I always appreciate feedback, questions, and conversation. Feel free to reach out by replying to this email!