Joey Bose

The goal of this Phase 1 study is to investigate the safety of CYT-108, our experimental recombinant protease inhibitor drug candidate for osteoarthritis, in a population of patients suffering from osteoarthritis of the knee. The main questions this study aims to answer are:

(1) Are two doses of CYT-108, delivered 12 weeks apart, safe when injected directly into the joint?

(2) Does administration of CYT-108 result in a reduction in pain, stiffness, and improvement in daily… Show more

The goal of this Phase 1 study is to investigate the safety of CYT-108, our experimental recombinant protease inhibitor drug candidate for osteoarthritis, in a population of patients suffering from osteoarthritis of the knee. The main questions this study aims to answer are:

(1) Are two doses of CYT-108, delivered 12 weeks apart, safe when injected directly into the joint?

(2) Does administration of CYT-108 result in a reduction in pain, stiffness, and improvement in daily physical function?

Participants will either receive a placebo (Phosphate Buffer Saline, PBS) or CYT-108, and will be asked to report their pain/stiffness at weeks 1, 4, 8, 12, 16, and 26 (in a physician's office) after the initial injection, using a questionnaire to be provided by the physician. In addition to reporting the magnitude of pain, participants will also be asked about the onset of pain reduction. Researchers will compare the pain/stiffness scores between the CYT-108-treated to placebo-treated groups along the 26 week duration of the study. Participants will also receive blood draws along the course of the study, and researchers will analyze this blood for the presence of cartilage degradation product in attempt to identify "disease modification" (i.e., a reduction in cartilage degradation) in response to CYT-108 treatment. Show less

The purpose of this study was to determine the toxicokinetics (TK) of CYT-108 when given once a week to female dogs via subcutaneous (SC) injection for at least 3 weeks (total of three doses).

Doses were administered weekly via SC injection on Days 1, 8, and 15. Blood samples were collected on Days 1, 8, and 15 before the dose and at various time points after the dose. Blood samples were also collected on Day 22 before euthanasia. Predose samples collected on Days 8, 15, and 22 were… Show more

The purpose of this study was to determine the toxicokinetics (TK) of CYT-108 when given once a week to female dogs via subcutaneous (SC) injection for at least 3 weeks (total of three doses).

Doses were administered weekly via SC injection on Days 1, 8, and 15. Blood samples were collected on Days 1, 8, and 15 before the dose and at various time points after the dose. Blood samples were also collected on Day 22 before euthanasia. Predose samples collected on Days 8, 15, and 22 were adjusted to 168 hours postdose concentrations for Days 1, 8 and 15, respectively.

The samples were analyzed for CYT-108 at Labcorp Madison to generate this TK report. Serum samples were also taken for anti-drug antibody (ADA) analysis on Days 1, 8, and 15 before dosing and at 24 and 48 hours after dosing. Samples were also collected before euthanasia on Day 22. Only specific serum samples were analyzed for ADA at Goodwin Biotech.

Due to limited exposure on Days 8 and 15, the dose exposure relationships between evaluation days could not be assessed. Tmax was observed at 24.0 hours postdose on Day 1 and at 8.00 hours postdose on Day 8 (N=1).

The incidence of ADA induction to CYT-108 was 0% (0 out of 4) for the 0 mg/kg/dose group on Days 1, 8, and 15. For the 5 mg/kg/dose group, the incidence of ADA induction to CYT-180 was 0% (0 out of 6) before dosing on Day 1, and was 100% (6 out of 6) at 24 hours after dosing on Days 8 and 15. For Animal D0106 (5 mg/kg/dose), all serum samples collected for ADA were positive on Days 1, 8, 15, and 22.

All animals in the 5 mg/kg/dose group showed positive results for ADA and had limited exposure on Days 8 and 15. Therefore, all animals were included in descriptive statistics and TK analysis. Although it cannot be definitively determined due to lack of comparison data, positive ADA likely resulted in limited to no CYT-108 exposure on Days 8 and 15. Show less

This study evaluated the toxicity and determined the toxicokinetics of the test article, CYT 108, when administered once weekly via subcutaneous injections to female dogs for at least 3 weeks (total of three doses). This study was conducted under GLP conditions and is considered IND-enabling.

The intended dose route in humans is intra-articular. However, due to limited space in the joint of dogs, the dose route used for the current study was subcutaneous injection, and doses were 10x the… Show more

This study evaluated the toxicity and determined the toxicokinetics of the test article, CYT 108, when administered once weekly via subcutaneous injections to female dogs for at least 3 weeks (total of three doses). This study was conducted under GLP conditions and is considered IND-enabling.

The intended dose route in humans is intra-articular. However, due to limited space in the joint of dogs, the dose route used for the current study was subcutaneous injection, and doses were 10x the human dose. Dogs historically have been used in safety evaluation studies and are recommended and accepted by appropriate regulatory agencies. The proposed dose for intra-articular injection for Osteoarthritis in humans is 0.5 mg/kg, which is based on efficacy and safety studies. Based on the FDA recommendations, the subcutaneous dose for the current study was calculated at 10x the human dose.

Dose formulations were administered once on Days 1, 8, and 15 of the dosing phase by subcutaneous injection at a dose volume of 1 mL/kg. Doses were based on the most recently recorded scheduled body weight. Day 1 of the dosing phase was defined as the first day of dosing for each cohort. Blood samples were taken prior to dosing and analyzed for anti-drug antibodies, serum chemistry and hematology, and PK clearance.

Administrations of 5 mg/kg/dose CYT-108 was well-tolerated. Microscopic findings included slightly decreased lymphocytes in the thyroid of one subject which correlated with decreased thymus weights, minimal fibrosis and increased incidence of minimal mononuclear infiltrate injection site. The mild severity of these findings and lack of impact on animal health led to them being considered nonadverse for this dose. All subjects displayed positive ADA results and had limited to no CYT-108 exposure on Days 8 and 15. Mean maximum observed concentration (Cmax) and area under the concentration-time curve (AUC) values for females on Day 1 were 15.4 µg/mL and 1420 h*µg/mL, respectively. Show less

The emergence of COVID-19 could not have come at a better time for the company. Cytonics’ preclinical study in osteoarthritis clearly demonstrated the safety and anti-inflammatory effects of CYT-108 and is convincing evidence that the drug is a viable candidate for human clinical studies. It just so happens that the inflammatory cascade (cytokine storm) that leads to cartilage damage in arthritic joints is almost identical to the hyperinflammation of the lungs that leads to death in COVID-19… Show more

The emergence of COVID-19 could not have come at a better time for the company. Cytonics’ preclinical study in osteoarthritis clearly demonstrated the safety and anti-inflammatory effects of CYT-108 and is convincing evidence that the drug is a viable candidate for human clinical studies. It just so happens that the inflammatory cascade (cytokine storm) that leads to cartilage damage in arthritic joints is almost identical to the hyperinflammation of the lungs that leads to death in COVID-19 patients. Serendipity, blind luck, karma… all words that describe how Cytonics feel about the potential for CYT-108 to effectively treat the life-ending symptoms of COVID-19. CYT-108 has been designed to inhibit the “cytokine storm” that leads to lung inflammation and eventual death. There are currently no effective therapies on the market (the FDA has approved remdesivir and convalescent plasma, but neither have demonstrated substantial improvement in patient survival and are dubious at best). If CYT-108 demonstrates efficacy in bringing down the levels of the SARS-CoV-2 virus and inhibiting the cytokine storm in a preclinical model of COVID-19, the drug may be eligible for Emergency Use Authorization from the FDA to expedite the drug approval pathway in humans. Show less

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 this pilot preclinical study… Show more

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 this pilot 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.

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 presentation). Show less