Review of where Kimera Labs fits into sphere of exosome companies

Today’s post takes a close look at the exosome manufacturer Kimera Labs in the context of the main exosome companies.

What are exosomes?

Exosomes are microscopic bubbles or vesicles produced by cells. Exosomes contain many cellular substances that are biologically active. Some of these materials may be helpful clinically, while others could pose risks. Clinical outcomes likely depend on a vast array of factors including the cell type making the exosomes, how the vesicles are harvested and stored, the donor, and the recipient. Yes, it’s complicated and too often exosomes have been portrayed as always beneficial.

Exosomes have potential as cell therapies, but it’s early days. The agency also has made clear it generally views exosome products as drugs. That means manufacturers and clinics cannot market them for clinical use without FDA approval. And the FDA has not approved any exosome therapy.

Yet they’ve sometimes been marketed without FDA approval.  Tens of thousands of patients have reportedly paid for and received “exosome therapy” in the past. If accurate, how is that possible? Note that part of the explanation may be that it was only in late 2019 that the FDA clearly said exosomes were drugs. Prior to that things were not so clear. Some marketing of exosomes may have occurred within a regulatory gray zone, but other marketing seems to clearly have been much later.

What are the main exosome companies today and where does Kimera fit in?

What is Kimera Labs?

Kimera Labs is a Florida biotech. It’s focused on manufacturing exosomes.

Duncan Ross, Ph.D. founded Kimera in 2012.

It was potentially the first large-scale exosome manufacturing company. Kimera makes exosomes from various kinds of cells including mesenchymal cells like MSCs from birth-related tissues.

The main product is something called XoGlo. You can see a video tour of their lab space below.

Two other well-known exosome companies are Direct Biologics and Organicell. They both have FDA INDs for exosomes for COVID. Kimera is still working to get its first IND. This strikes me as a bit puzzling since I knew of Kimera many years before I heard of the other two firms.

What’s the history here? Let’s work our way back.

Marketing by exosomes companies and potential clinical use of products

In a 2022 PR announcing a trade secrets lawsuit, Kimera Labs mentions the surprising scope of apparent past clinical use of their product XoGlo (emphasis mine):

“To date, the company’s first publicly available isolated exosome product, XoGlo^®, has treated over 120,000 patients for a variety of investigational indications. Exosomes have been referenced in numerous peer-reviewed scientific publications and exhibit anti-inflammatory and growth instantiating properties. The success of these therapies has led to a current FDA IND application for post COVID-19 symptom treatment.”

To me, this feels like a classic example of the cart before the horse. An IND would have to be cleared by the FDA before a drug is even tested in clinical trials. Then other requirements based on clinical trial results must be met before an exosome drug is marketed to patients or to physicians who may use it as a treatment for their patients. Note that exosomes have often been marketed directly to care providers.

The cautious word “investigational” is in the quote above, but so are the words “patients” and “treated.”

Did these “treatments” happen prior to the FDA clearly defining exosomes in late 2019 as drugs requiring pre-market approval?

Kimera Labs 2020 Letter from the FDA

In 2020 Kimera received an untitled letter from the FDA on marketing.

Here’s the key quote from the FDA:

“Kimera Labs markets exosome products to treat numerous diseases or conditions, including some that are serious or life-threatening. These products are administered by various routes of administration, including intravenously. Kimera Labs also supplies its products to health care providers such as Dr. Spiel, who is both a Clinical Consultant for Kimera Labs and President of Regenerative Solutions of New Jersey. Regenerative Solutions of New Jersey markets these products to mitigate, prevent, treat, or cure Coronavirus Disease 2019 (COVID-19).

You and your firm market your exosome products to treat diseases or conditions such as Parkinson’s disease, Multiple Sclerosis, brain injuries, diabetes, stroke, and spinal cord injuries.

…It appears that the above-referenced exosome products would be regulated as drugs…”

Note that Spiel is no longer part of Kimera. Did other Kimera leadership realize what Spiel was doing at that time or only later?

Kimera vs. Direct Biologics and Organicell

Circling back to the IND issue in the present, how do Direct Biologics and Organicell have INDs, but Kimera does not?

As best as I can tell, all three firms marketed exosomes for health conditions including COVID-19 at some point. For example, see this piece on Organicell. Why did only Kimera get a warning letter? Did the FDA not consider past activities by Direct Biologics and Organicell on exosomes to be non-compliant?

More generally I wondered: does the FDA even consider past potential non-compliant marketing in evaluating any new IND applications? I asked FDA expert Patti Zettler about this. Here were her thoughts:

“The short answer, is, I don’t think anything FDA regulations expressly list previous, potentially-non-compliant activities as a factor for FDA to consider. But previous conduct might be relevant to certain considerations specified in the regulations, and I’d think FDA, in pre-IND meetings or other communications, could always discuss any such concerns with sponsors.

The slightly longer answer is, under FDA regulations (21 CFR 312.40), an IND goes into effect 30 days after FDA receives it, unless FDA notifies the sponsor that the studies in the IND are subject to a clinical hold. FDA regulations (21 CFR 312.42) specify the grounds on which FDA can impose a clinical hold, none of which expressly mention previous potentially-non-compliant conduct. That said, it might be that previous conduct that FDA has concerns about is relevant to the clinical hold grounds. For example, perhaps previous conduct in certain circumstances might be relevant to determining whether clinical investigators are qualified or whether human subjects will be exposed to an unreasonable and significant risk. And, as noted above, it might be that FDA discusses any such concerns it has with sponsors in pre-IND meetings or other discussions.”

To be clear, only the FDA decides whether any activity is non-compliant. I’m not saying any of these firms were non-compliant beyond anything the FDA itself might have said. Still, there are legitimate questions about the compliance of the marketing of exosomes in this space for health conditions at certain times in the past overall.

What other factors could explain the difference in IND progress?

Direct Biologics has published data on their product ExoFlo so that might help them with the FDA. While I have some big concerns and questions about the ExoFlo clinical trial paper, it is out there and underwent peer review.

Note that related to Direct Biologics, I wrote last year about how during Commissioner Hahn’s tenure some of his texts seemed to indicate that strong political pressure was exerted on him and the FDA to help the firm with an IND.

Direct Biologics has moved forward quickly and started a Phase III COVID trial. I’m very curious to see how that goes.

What about Organicell?

The Organicell IND is for their investigational exosome product Zofin for COVID long-haulers.

A PubMed search for papers mentioning Organicell gave eleven results, although not all of them may be about Zofin. Note that Zofin was previously called “Organicell Flow”.

I haven’t had a chance to dig into those papers to see their strengths or weaknesses. I’m also less familiar with this company in general so it’ll require more research.

Note that Organicell is now also a publicly-traded firm.

It’s also important to say that there are many other exosome companies as well beyond those mentioned in today’s post.

Looking ahead on exosome companies

It could be a while before the FDA approves an exosome therapy. There’s a good chance it will eventually happen for any specific disease.

There is growing interest in the use of exosomes for cosmetic purposes as well. It’s not clear how the FDA would view such marketing in the U.S. My prediction is that cosmetics containing exosomes probably would be defined as drugs.

What news might we see in this space this year?

Maybe Kimera will get its IND in 2023, which would be a step in the right direction. I reached out to Kimera for comment on where the company stands today and I will post if I get a response that I can include here.

Will Direct Biologics publish data from their completed double-blinded, randomized, placebo-controlled Phase II clinical trial? I hope so as it will be very interesting.

There are also many different lawsuits in the exosome arena right now (e.g., search on PaceMonitor for Direct Biologics or Kimera Labs). Some of that litigation is likely to have an impact as well either this year or next.

Overall, this is a fascinating emerging area, but the commercial side is not easy to navigate.

References

• PubMed search for papers mentioning Organicell. 
• PubMed search for ExoFlo papers.
• The only PubMed result I found for Kimera Labs was an author of a paper on something else disclosing a role with that firm.
• FDA statement in late 2019 that exosomes are generally drug products.
• Organicell Zofin clinical trial listing.