Biosplice Announces Data from Recent Clinical Trials in Knee Osteoarthritis and the Initiation of a New Phase 3 Trial

Robust two-year X-ray results of medial joint space width (mJSW) and significant pain response in patients with earlier disease highlight the potential of lorecivivint to be a first-in-class, structure-modifying drug for the treatment of knee osteoarthritis

SAN DIEGO, Nov. 11, 2022 (GLOBE NEWSWIRE) -- Biosplice Therapeutics, Inc. (“Biosplice”), a clinical-stage biotechnology company pioneering first-in-class therapeutics based on small-molecule inhibition of CLK/DYRK kinases, announced today highlights from three Phase 3 clinical trials, OA-07, OA-10 and OA-11 for its knee OA drug candidate, lorecivivint. Recent Biosplice data, particularly in the OA-07 long-term efficacy trial, demonstrate both symptomatic and structural benefit in treating knee osteoarthritis in patients with early joint damage, defined as KL2 and early-stage KL3 patients, which represent an estimated 70% of the knee OA population.

Upon the conclusion of OA-11, a 12-month study, completing participants were able to enroll in an additional Phase 3 trial, OA-07, which served as a long-term extension study with multiple injections. During the first year of the OA-07 study, patients and investigators remained blinded and patients received injections of LOR on an annual basis, allowing Biosplice to capture both long-term and repeat-injection safety and efficacy data. These data show clinically significant improvement in medial joint space width relative to placebo, with an effect size of 0.13 and 0.20 millimeters in overall KL2 and early-stage KL2 patients, respectively. Moreover, OA-07 data demonstrate a significant improvement in WOMAC Pain and robust trends in Pain NRS (daily pain score) as well as WOMAC function in all subjects. Strong observed efficacy in this OA-07 study, along with data from the OA-10 trial, helped form the basis of trial design for Biosplice’s next Phase 3 trial, OA-21, as described below.

In two prior Phase 3 clinical trials, OA-10 and OA-11, lorecivivint, demonstrated clinical efficacy in earlier, less structurally damaged patients, although these trials fell short of reaching statistical significance in their primary endpoints of Pain NRS (daily pain score) at week 12 with all subjects. Extensive analysis has identified two potential confounding factors: participants in OA-10 and OA-11 had the most structurally advanced disease enrolled in the program to date and adequate separation from placebo was potentially suppressed by mobility-limiting COVID lockdown protocols, as the trials were conducted during the COVID pandemic. Confounding effects of the pandemic on activity levels and pain PROs in knee OA patients have been widely reported¹.

Consistent with observations of OA-07 data noted above, the six-month long OA-10 study demonstrated that lorecivivint outperformed placebo in the KL2 and early-stage KL3 patients (i.e., less structurally damaged patients), a key subgroup that represents the majority of the knee OA patient population. This subgroup showed consistent benefit with lorecivivint over placebo in multiple measurement time periods and metrics, such as pain NRS, WOMAC pain, WOMAC function and patient global assessment of disease activity in the OA-10 study.

Consistent with the clinical program to date, lorecivivint continued to appear safe and well-tolerated in the recently completed studies, with no safety signals with repeat injections.

“Healthcare professionals need an approach for treating knee osteoarthritis that can provide durable pain relief, improve functionality, and be safely utilized over a long period of time,” said Biosplice Chief Medical Officer, Yusuf Yazici, MD. “Biosplice aims to provide physicians a knee osteoarthritis treatment that does not compromise between efficacy and safety. Our local, intra-articular injection hopes to provide a safe, effective and much-needed structure-modifying treatment option to physicians and patients alike. Our data to date suggest that earlier, less structurally damaged patients provide the ideal target population to study in our next Phase 3 trial, which we expect will further support the beneficial effects of lorecivivint in this very important patient population.”

Biosplice conducted a meeting with the FDA in Q3 2022, in which its next phase 3 study for lorecivivint was discussed. Designated OA-21, this next phase 3 trial is designed as a 16-week study with a primary endpoint of Pain NRS at 12 weeks and enrollment is expected to begin in Q4 2022. This study will further evaluate the impact of lorecivivint on knee osteoarthritis pain and function and has been modeled after the early, less structurally damaged patient population that has shown consistent responses across Biosplice’s Phase 2 and Phase 3 clinical trials.

Biosplice will be presenting data in three poster presentations and one oral presentation at the 2022 ACR Annual Meeting as outlined below.

Oral presentation details:

Poster presentation details:

Further details can be found on the ACR website at https://www.rheumatology.org/Annual-Meeting. A copy of the presentation materials can be accessed by visiting the Publications section of the Biosplice website following the conclusion of the presentations.

About Biosplice
Biosplice is developing first-in-class, small-molecule therapeutics based on pioneering science of alternative pre-mRNA splicing. Stemming from foundational discoveries in Wnt pathway modulation, Biosplice has elucidated novel biology linking CLK/DYRK kinases to the therapeutic regulation of alternative splicing. Alternative splicing is an essential biological mechanism that regulates the diversification of proteins in a cell, which, in turn, determines cell type and function. Biosplice’s target class governs the selection of tissue-specific mRNA splice sites, making them attractive, druggable targets within the cellular “command and control” center.

Biosplice’s drugs in clinical development include lorecivivint for osteoarthritis (in Phase 3), cirtuvivint for numerous cancers, and a broad pipeline that ranges from Alzheimer’s disease to other degenerative conditions. Learn more at https://www.biosplice.com

Corporate Contact:
Erich Horsley
Biosplice Therapeutics, Inc.
erich.horsley@biosplice.com
858-365-0200

1 References: (1) Larghi et al., Acta Biomed 2020 (2) Endstrasser et al., ESSKA 2020