March 30, 2022
VYNE Reports Positive Preclinical Data for Intra-Articular Injection of Pan-BET Inhibitor, VYN201, in an In Vivo Model of Rheumatoid Arthritis

BRIDGEWATER, N.J., March 30, 2022 (GLOBE NEWSWIRE) — VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a biopharmaceutical company focused on developing proprietary, innovative, and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced positive preclinical data in a rheumatoid arthritis (“RA”) model from its VYN201 program. The data demonstrated that VYNE’s pan-BET inhibitor VYN201 used as an intra-articular injection resulted in significant inhibition of inflammation in a validated animal model of RA. The data supports the potential to develop VYN201 as a locally-administered intra-articular treatment for an autoimmune joint disease.

“The data from this preclinical model in rheumatoid arthritis is the latest to demonstrate VYN201’s potential to deliver a potent anti-inflammatory response and supports the potential broad therapeutic profile for VYN201 as a locally-administered pan-BET inhibitor,” said David Domzalski, Chief Executive Officer of VYNE. “We remain on track to initiate a first in-human clinical trial for VYN201 in the second half of this year.”

Anti-Collagen Antibody Induced Mouse Model of RA

RA is a chronic autoimmune and inflammatory disease with an average prevalence of 0.5–1.0% in the population worldwide. RA is characterized by inflammation of the synovial membrane, resulting in progressive cartilage damage and bone erosion. Symptoms of RA most commonly include pain, swelling, redness and stiffness in the affected joints, limiting the range of motion.

In this validated preclinical model for RA, inflammatory arthritis was induced in BALB/c mice by systemically injecting a mixture of four arthritogenic monoclonal antibodies against collagen II at day 1. In addition, the mice received a lipopolysaccharide injection systemically at day 4 to stimulate an acute systemic inflammatory response. Each treatment group (n=7 per group) was injected with either (i) an intra-articular dose of VYN201 vehicle, (ii) an intra-articular dose of VYN201, (iii) an intra-articular dose of dexamethasone (1mg/kg) or (iv) a systemic dose of dexamethasone (1mg/kg, via intraperitoneal injection). The intra-articular doses were administered on days 0, 3, 6 and 9 while the dexamethasone systemic injections were given daily beginning at day 0 through 11. For the VYN201 treatment groups, four doses of VYN201 were evaluated (at concentrations ranging from 0.01 to 10mg/kg). Each animal treated with the intra-articular injections received the injection in the ankle of one rear paw. The untreated rear paw was assessed to evaluate any potential anti-inflammatory systemic effect. Treatment response was evaluated based on an assessment of paw thickening or swelling (in millimeters) and arthritis scoring based on a five-point composite severity scale of redness, swelling of the ankles and wrists, and paw thickness. Scoring in this model ranges from 0 (normal) to 4 (extensive signs and symptoms of arthritis).

Key findings:

  • Paw Thickening: VYN201 demonstrated marked inhibition of paw thickening at the 1 and 10mg/kg doses. At both doses, the inhibition of paw thickening was statistically significant in the treated paw relative to the untreated rear paw on day 12 (p<0.01).”
  • For these VYN201 treatment groups, mean paw thickness at baseline (day 0) was 2.08 mm.
  • For the 10mg/kg dose, the average paw thickness at day 12 was 3.48 mm in the untreated paw versus 2.17 mm in the treated paw, representing a 37.6% reduction.
  • For the 1mg/kg dose, the average paw thickness at day 12 was 2.98 mm in the untreated paw versus 2.18 mm in the treated paw, representing a 26.8% reduction.
  • Results with these two doses were numerically superior to intra-articular dexamethasone and consistent with the systemic dexamethasone treatment.
  • Arthritis Score: Limbs treated with VYN201 at the 1 and 10mg/kg dose levels had an average arthritis score of 0.57 and 0.67, respectively, or near normal. The arthritis score was significantly lower in the treated paw at both doses relative to the non-treated paws on day 12 (p<0.05).
  • At the 10mg/kg dose, the average arthritis score was 0.67 in the treated paw versus 3.33 in the untreated paw, representing a 79.9% reduction.
  • At the 1mg/kg dose, the average arthritis score was 0.57 in the treated paw versus 2.43 in the untreated paw, representing a 76.5% reduction.
  • Limbs treated with intra-articular dexamethasone received an average arthritis score of 1.3, indicating mild symptoms. These animals had signs of redness and swelling of the ankle/wrist or apparent redness and swelling limited to individual digits.

Locally Acting Anti-Inflammatory Effect:

Demonstrated improvement in signs and symptoms of joint inflammation were observed in the limbs of animals treated with VYN201, and no treatment effect was observed in untreated limbs, suggesting a locally acting anti-inflammatory effect of VYN201. In contrast, animals that received systemic dexamethasone experienced a treatment effect in all limbs.

Treatment tolerability was evaluated based on changes in body weight. Animals treated with systemic dexamethasone experienced continued weight loss throughout the study while all other treatment groups experienced improved body weights following recovery from the RA stimulant.