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Cytonics Achieves Preclinical Study Milestone

8 Aug 2020
  • The toxicology results indicate that CYT-108 is safe to administer when exposed to the systemic circulation at a  highly-concentrated (10x) dose.
  • The efficacy results indicate that CYT-108 has therapeutic effects (as measured by 6 independent metrics of cartilage and joint health) when injected into damaged, arthritic joints. See slides 16-18 in the presentation.
  • Taken together, the results of the preclinical study indicate that CYT-108 may be a safe, viable therapeutic for treating osteoarthritis and associate joint damage. These results will be confirmed in a larger preclinical study and discussed with the FDA before entering Phase 1 human trials.
  • This was a key milestone on the path to approval and commercialization, and will be used to substantiate our request to enter Phase 1 human clinical trials.
  • This study is the most important trial we have conducted thus far, and is a key driver of the valuation of the company!
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see slides 16 and 17 for preclinical study results

From the lab to hospital bed

The journey to commercialization for an experimental drug is long and fraught with risk. It is no small undertaking, and only the boldest scientists and physicians attempt to translate their research into clinical therapies. As a former cancer biologist, I can attest to the incredible amount of creativity and ingenuity that is pervasive in academic institutions. Every PhD in the lab has an awesome idea on how to treat their disease of interest and may even have some data to prove it. However, there is a large discrepancy between the research generated in an academic lab (which is usually more exploratory than treatment-related) and the clinical research performed by pharmaceutical companies. The clinical viability of those academic ideas is not obvious often never translates into an FDA approved therapy. That’s where preclinical studies come into play. After an experimental drug is discovered or engineered and tested in a laboratory setting (using some petri dish-based or mouse model of the disease to see if the drug has any potential), a more involved set of experiments must be performed in large animals (which are more anatomically and physiologically similar to humans than rodents) to determine the safety, toxicity, and possible efficacy of the drug in treating the disease of interest. These experiments are preclinical and provide the FDA with enough information to determine whether the experimental drug is safe and promising enough to test in humans (Phase 1-3 clinical trials). At the end of the day, safety is paramount, and we must be certain that we are not going to harm anyone when we conduct a our first-in-human study (Phase 1 trial).


The preclinical data is in, and CYT-108 is ready for prime time!

Cytonics is on the verge of human clinical trials for its experimental drug candidate, CYT-108, a synthetic variant of the naturally-occurring A2M blood protein that has been demonstrated to reverse the effects of osteoarthritis of the joint. Preliminary preclinical data (below) demonstrates CYT-108’s efficacy in preserving the cartilage and surrounding tissues (e.g., synovial membrane) in a large animal model of post-traumatic osteoarthritis. In our preclinical study, osteoarthritis was induced by destabilizing the joints of the subjects, which induced cartilage damage and joint swelling similar to the damaging effects of osteoarthritis in humans. Regular treatments of CYT-108 (or placebo saline solution) were injected into the damaged joints along a 12-week treatment window. Pieces of the cartilage and surrounding tissues (bone, synovial membrane, meniscus) were examined to measure the cartilage-protective effects of CYT-108 and its ability to encourage joint remodeling/healing. The data below provides a snapshot of these results. In summary, administration of CYT-108 into the joint restored the damage caused by osteoarthritis to the cartilage (Fig 1) and synovial membranes (Fig 2) by ~60%! This damage was assessed using the modified OARSI scoring system, which is a grading scale that pathologists use to determine the damage to various tissues (on a microscopic level). This therapeutic trend was observed in 4 other measurements of cartilage, bone, and synovial membrane health (see slides 16-17 of the presentation)!


Figure 1. Intra-articular injection of our recombinant A2M variant, CYT-108, results in articular cartilage preservation and recovery of cartilage degradation in large animal subjects suffering from post-traumatic osteoarthritis. Histopathological macroscopic and microscopic grading (modified OARSI scoring system) of the articular cartilage in Groups 1-3 reveals that treatment with  CYT-108 results in recovery of ~57% of the damage to the cartilage structure in the knee joint that occurs due to induced joint instability and cartilage damage. These results indicate that CYT-108 has therapeutic activity against the degradation of articular cartilage that results from the pathogenesis of osteoarthritis. Taken together with the toxicology and immunogenicity data (not shown), this body of preliminary preclinical data indicates that CYT-108 may be a safe, viable treatment for osteoarthritis. Error bars +/- SEM.


Figure 2. Intra-articular injection of our recombinant A2M variant, CYT-108, results in thinner, healthier synovial membranes in large animal subjects suffering from post-traumatic osteoarthritis. Histopathological microscopic grading (modified OARSI scoring system) of the synovial membranes of subjects in Groups 1-3 reveals that treatment with CYT-108 results in recovery of ~60% of the cellular thickening and cell layer accumulation of the synovial membrane that occurs due to trauma and inflammation of the knee joint. These results indicate that CYT-108 has therapeutic activity against the pathological changes in the synovial membrane that occur as a result of the pathogenesis of osteoarthritis. Taken together with the toxicology and immunogenicity data (not shown), this body of preliminary preclinical data indicates that CYT-108 may be a safe, viable treatment for osteoarthritis. Error bars +/- SEM.

Cartilage Structure

Intra-articular injection of our recombinant A2M variant, CYT-108, results in thinner, healthier synovial membranes in large animal suffering from post-traumatic osteoarthritis. Histopathological grading (modified OARSI scoring system) of the synovial membranes of subjects in Groups 1-3 reveals that treatment with CYT-108 results in recovery of ~60% of the cellular thickening of the synovial membrane that occurs due to trauma and inflammation of the articular cartilage. These results indicate that CYT-108has therapeutic activity against changes in the synovial membrane that occur due to the progression osteoarthritis. Taken together with the toxicology and immunogenicity data (not shown), this body of preliminary preclinical data indicates that CYT-108 may be a viable treatment for osteoarthritis.

Error bars +/- SEM

Synovial Membrane

Intra-articular injection of our recombinant A2M variant, CYT-108, results in articular cartilage preservation and recovery of cartilage degradation in large animal subjects suffering from post-traumatic osteoarthritis. Histopathological grading (modified OARSI scoring system) of the articular cartilage in Groups 1-3 reveals that treatment with CYT-108 results in recovery of ~57% of the damage to the cartilage structure that occurs due to the development of osteoarthritis. These results indicate that CYT-108 has therapeutic activity against the degradation of articular cartilage that results from the development of osteoarthritis. Taken together with the toxicology and immunogenicity data (not shown), this body of preliminary preclinical data indicates that CYT-108 may be a viable treatment for osteoarthritis.

Error bars +/- SEM

Safety first

The FDA’s #1 concern is safety. And rightfully so. If an experimental drug can be proven safe in preclinical animal studies then it will probably also be safe to administer to humans at comparable dosages. We decided to take things one step further and investigate the effects of CYT-108 when exposed directly to the system circulation by subcutaneous (under the skin) injection (remember, CYT-108 is injected into damaged joints, which are encapsulated by a membrane and not rich with blood vessels). A 10x dose was injected into healthy animal subjects and the effects on organ health and immune system response were analyzed. The results could not have been better. Not only did we not detect any immune response (as measured by an increase in antibody generation) but the injection of an extremely high dose of the drug did not damage the internal organs. I’m not exaggerating when I say that upon receiving these results the company breathed a collective sigh of relief! The largest hurdle thus far in our path to FDA approval has been cleared with room to spare.


One down, one to go

This preclinical study was the single-most important dataset that the company has ever generated. It presents a strong body of evidence suggesting that CYT-108 is a viable treatment for osteoarthritis: there are clear trends that it is therapeutically active measured by multiple measurements of cartilage and tissue integrity, and it is well-tolerated even when injected at extremely high doses. We have already submitted our data to the FDA for review and will receive their feedback by Q3 2020. We expect that they will be pleased with the safety data and will most likely ask us to repeat the preclinical experiment with more subjects just to make sure that the safety and efficacy results are reproducible. We did it once, and we can do it again. 


“The results of our study look very promising,” said Joey Bose, President of Cytonics. “The purpose of this pilot preclinical study was to examine whether CYT-108 is a feasible drug candidate for treating osteoarthritis and safe to administer to patients. Importantly, CYT-108 was well-tolerated when injected into the joint and no adverse effects were observed when administered at a 10-fold higher dose under the skin (subcutaneous injection). Moreover, we observed cartilage-protective effects of CYT-108 when administered into arthritic joints. CYT-108 is a recombinant variant of the naturally-occurring A2M protein, which is a well-characterized anti-inflammatory agent due to its ability to “scavenge” for pro-inflammatory molecules (cytokines) and inhibit the enzymes (proteases) that cause cartilage degeneration in osteoarthritis.  Prior to this study, Cytonics engaged the FDA and received feedback on proposed pre-clinical and Phase 1 clinical trial designs. This feedback was used to intelligently design the pilot study to ensure that the methods and endpoints conform to the FDA’s recommendations, as well as optimize the probability that CYT-108 will be deemed a viable candidate for Phase 1 human trials. We will consult with the FDA and repeat this preclinical study at higher power (i.e., more test subjects) to determine statistical significance of the observed results, but there is enough evidence to suggest that CYT-108 is safe to administer and is therapeutically active in the joint space. If approved by the FDA, CYT-108 will be a first-in-class biologic treatment for osteoarthritis, providing patients with the first safe and effective therapy to slow down the progression of the disease by preventing the cartilage breakdown.”