Caliway Announces Positive Data from CBL-0201EFP Phase 2-Stage 1 Study of CBL-514 in Treating Moderate to Severe Cellulite

• CBL-514 is the only non-invasive product that can improve 1-level of cellulite severity two weeks after a single treatment.
• The highest dose of CBL-514 treatment demonstrated the best efficacy, 87.5% of thighs achieved at least 1-level improvement in cellulite severity two weeks after CBL-514 treatment.
• The side effects of CBL-514 are relatively mild compared to the current cellulite treatment options and other injection treatments.
• Currently, there is no effective and safe cellulite treatment on the market. The global market for cellulite treatment is estimated to expand to $5.2 billion in 2028.

TAIPEI, June 28, 2023 /PRNewswire/ -- Caliway Biopharmaceuticals (Caliway), a Taiwan-based biopharmaceutical company focusing on breakthrough medical aesthetics and inflammatory medicine discovery of small-molecule therapeutics, today announced that the CBL-0201EFP Phase 2-Stage 1 results demonstrated the significant cellulite severity improvement with a single CBL-514 treatment. Cellulite is a skin condition currently without effective and safe treatment.

CBL-514, Caliway's lead candidate drug, is a non-surgical lipolytic injection that can reduce local fat precisely by inducing adipocyte apoptosis and lipolysis. The CBL-0201EFP Phase 2-Stage 1 data demonstrated that CBL-514 is the first and only non-invasive product that can significantly improve 1 level of cellulite severity two weeks after a single treatment.

"Current treatment modalities for cellulite of the lateral thighs are few and limited for various reasons. Although some improvement can be obtained from currently approved devices and injectables, the results are somewhat unpredictable, limited, moderately invasive, and not without some significant adverse events," said John H. Joseph, MD, director of Clinical Testing of Beverly Hills and the principal investigator of CBL-0201EFP study, "The results of the Phase 2 Stage 1 clinical trials on the use of a novel compound, CLB-514, to treat cellulite of the lateral thigh are encouraging."

Phase 2 Study of CBL-514 in Treating Cellulite

CBL-0201EFP is a U.S. FDA-approved, two-stage Phase 2 study evaluating the efficacy, safety, and tolerability of CBL-514 injection in treating subjects with moderate to severe Edematous Fibrosclerotic Panniculopathy (EFP), cellulite.

The first stage of CBL-0201EFP is an open-label, single ascending dose (SAD) study aimed to evaluate CBL-514's efficacy and determine the optimized dose for cellulite treatment. The study enrolled twelve subjects in three sequential escalating CBL-514 dose groups, including 40 mg, 60 mg, and 80 mg. Each subject was sequentially assigned to receive one course of allocated CBL-514 dose administrated subcutaneously on both sides of the posterolateral thighs. The efficacy and safety of CBL-514 were evaluated at Week 1, Week 2, and Week 4 post-administration.

The primary efficacy endpoint was evaluated by the total score change in modified Hexsel Cellulite Severity Scale (HCSS) compared to the baseline. The secondary efficacy endpoint was evaluated by the percentage of thighs with at least 1-level improvement in modified HCSS.

Preliminary Efficacy Data Summary of CBL-0201EFP Phase 2-Stage 1

The efficacy data are composed of all dosing groups in the stage 1 study. Each group includes four subjects with both thighs administrated with CBL-514 injection.

The percentages of the thighs with at least 1-level improvement in modified HCSS compared to the baseline in each dose group are listed below.

In all groups, over 50% of the thighs achieved at least 1-level cellulite severity improvement in modified HCSS at V5 (Week 4). In particular, in group 3, treated with a unit dose of 2 mg/cm² CBL-514, 87.5% of the thighs achieved at least 1-level cellulite severity improvement in modified HCSS at V4 (Week 2) and V5 (Week 4) after treatment compared to baseline.

In addition, the adverse event (AE) of the CBL-514 injection was relatively mild and well tolerated compared to the other injection treatments. It did not cause any depression or fibrosis in the treatment area.

The CBL-514 with a 2 mg/cm² unit dose administrated in group 3 demonstrated the best efficacy compared to the baseline. It will be used as the dose for CBL-0201EFP Phase 2-Stage 2 and the following cellulite clinical studies.

"This first-of-its-kind drug (CBL-514) had a majority of subjects demonstrating a 1-level improvement on a validated scale for lateral thigh cellulite judged by the principal investigator in as little as 2 weeks after treatment," said Dr. John Joseph, "The adverse event profile from a single injection was minor and well tolerated by the subjects. These early results are exciting and CLB-514 may show further benefit for treating cellulite of the lateral thigh with additional treatments over time."

Clinical Update on CBL-0201EFP Phase 2-Stage 2 Study

The subject recruitment of CBL-0201EFP Phase 2-Stage 2 Study is undergoing in five clinical sites in the US. It will enroll 20 subjects with moderate to severe cellulite. The study is expected to be completed in Q4 2023; the results are anticipated in Q1 2024.

About Cellulite (Edematous Fibrosclerotic Panniculopathy, EFP)

Cellulite is characterized by the nonpathological appearance of the dimpled skin surface (likened to orange peel, cottage cheese, or mattress appearance), which occurs on the thighs and buttocks. As many as 80 to 90% of women experience cellulite dimpling. The relief alterations of cellulite include depressions and raised areas. The depressions are caused by skin retraction by subcutaneous fibrous septa, while raised areas are projections of fat and subcutaneous structures to the skin surface.

The current treatment for cellulite includes non-invasive (medical devices and collagenase drug) and invasive options. However, their efficacy remains limited as the current treatment options can only treat cellulite temporarily. Additionally, most products would cause significant side effects after administration, including severe bruising, pain, and hyperpigmentation, making most patients reluctant to receive them. The clinical need for cellulite treatment remains unmet. The global cellulite treatment market size in 2022 was $3.3 billion. With a compound annual growth rate (CAGR) of 7.8%, the global market for cellulite treatment is estimated to expand to $5.2 billion in 2028.

About the CBL-0201EFP Phase 2 Study

The CBL-0201EFP study is a two-stage Phase 2 trial evaluating the efficacy, safety, and tolerability of CBL-514 in treating subjects with cellulite. CBL-514 will be administrated by subcutaneous injection at the treatment area of cellulite on both sides of the posterolateral thighs.

Hexsel cellulite severity scale (HCSS) is composed of five key morphological aspects, with a total cellulite severity score of 15. The severity of cellulite in the CBL-0201EFP Phase 2 study will be assessed with modified HCSS. The modified HCSS is composed of only three critical morphological aspects, including (A) the number of evident depressions, (B) the depth of depressions, and (C) the morphological appearance of skin surface alterations, with a total cellulite severity score of 9. The severity level of cellulite will be scored as mild, moderate, or severe, which will be determined by the total scores obtained from items A to C as illustrated in the table below.

This Phase 2 study has an integrated design consisting of a single ascending dose (SAD) part in stage 1 followed by a single-arm design in stage 2.

The CBL-0201EFP Phase 2-Stage 1 study (NCT05632926) is an open-label, single ascending dose (SAD) trial. Stage 1 will enroll 12 subjects with moderate to severe cellulite, and each group will enroll four subjects in three sequential escalating CBL-514 dose groups. Eligible subjects will be sequentially assigned to receive one course of CBL-514 injections at 40mg, 60mg, or 80mg administered by subcutaneous injection on both sides of the posterolateral thighs. After administration, the study evaluates a single CBL-514 injection's efficacy and safety profile at Week 1, Week 2, and Week 4.

The CBL-0201EFP Phase 2-Stage 2 study (NCT05836779) is an open-label trial that will enroll 20 subjects with moderate to severe cellulite. It will evaluate the efficacy, safety, and tolerability of CBL-514 with up to two treatments, larger treated areas, and higher total doses. All the subjects will receive CBL-514 treatment, and the treatment dose will be based on the PI's evaluation of the cellulite severity. Subjects will receive up to 320 mg of CBL-514 per treatment session at intervals of approximately four weeks. After the last treatment, the efficacy and safety will be evaluated at follow-up visits at V4(Week 4) and V5 (Week 12).

About CBL-514

CBL-514, a first-in-class small-molecule drug, is an injection lipolysis drug that can induce adipocytes apoptosis and lipolysis to reduce subcutaneous adiposity in treatment areas in animal studies without causing any systematic side effects on the central nervous system, cardiovascular system, and respiratory system. Caliway's nonclinical studies showed that CBL-514 inhibits the cell survival kinase DYRK1b, upregulates the apoptosis mediators caspase 3 and Bax/Bcl-2 ratio, and then induces dose-dependent adipocyte apoptosis in vivo and in vitro.

Caliway is investigating multiple indications for CBL-514, including non-invasive fat reduction (reducing subcutaneous fat), Dercum's disease, cellulite, and lipoma treatment.

About Caliway Biopharmaceuticals

Caliway Biopharmaceuticals (Caliway), is a Taiwan-based, clinical-stage biopharmaceutical company driven to breakthrough drug discovery of novel small-molecule therapeutics to help patients suffering from illness or life-threatening diseases. In Caliway, we aim to become an innovative pharmaceutical leader in medical aesthetics and inflammatory disease. For more information, please visit: www.Caliway.com.tw/en

SOURCE Caliway Biopharmaceuticals