HanAll Biopharma Announces Results from Phase III randomized, double-masked active treatment-controlled VELOS-3 Trial Evaluating Tanfanercept 0.25% for Treatment of Dry Eye Disease

Tanfanercept did not demonstrate statistical significance in either of the primary outcome measures of improvement in central corneal staining score (CCSS) or in improvement in Eye Dryness Score (EDS) assessed at week 8 in subjects with dry eye disease (DED),compared to vehicle.

However,tanfanercept did demonstrate a highly statistically significant improvement on one of the secondary outcome measures,Schirmer testing of tear volume.

Tanfanercept demonstrated a similar safety profile compared to vehicle,consistent with the findings of the previous VELOS-1 (Phase II) and VELOS-2 (Phase III) trials.

HanAll will continue to examine the VELOS-3 data as well as aggregate data across all tanfanercept trials to refine the design for the next study.

ROCKVILLE,Md. and SEOUL,South Korea,May 19,2023 -- HanAll Biopharma Co.,Ltd. (KRX: 009420. KS),a global biopharmaceutical company committed to discovering and developing innovative medicines for patients,announced results from the Phase III VELOS-3 trial evaluating the safety and efficacy of tanfanercept,a novel,topical anti-inflammatory treatment being studied for the treatment of dry eye disease (DED) in subjects diagnosed with moderate to severe DED.

The Phase III VELOS-3 trial did not demonstrate statistical significance for either of the two primary efficacy endpoints: improvement from baseline in central corneal staining score (CCSS) and in improvement from baseline in Eye Dryness Score via Visual Analogue Scale (VAS) assessed at week 8 in subjects with dry eye disease (DED),relative to vehicle.

However,VELOS-3 did demonstrate statistically significant improvement (p<0.001) in the secondary efficacy endpoint of unanesthesized Schirmer testing to quantify change from baseline in tear volume in tanfanercept treatment arm relative to vehicle arm assessed at week 8.

Additionally,further analysis of Schirmer data in VELOS-3 revealed that the proportion of subjects whose Schirmer test improved from baseline by 10mm or greater as assessed at week 8 was statistically significant (p<0.001) in the tanfanercept treated arm (15%) relative to vehicle arm (4%).

Correspondingly,in a post hoc analysis of VELOS-2 data (a previous phase III study),when the subset of subjects that met VELOS-3 inclusion criteria are examined,data from Schirmer testing also meets statistical significance (p<0.05) for improvement in subjects in the tanfanercept arm relative to subjects in vehicle control arm as assessed at week 8.

It is notable that per the FDA's 2020 Draft Guidance on dry eye drug development,as an acceptable primary efficacy endpoint option,the FDA lists the measurement of a statistically significant difference between the percentage of patients achieving a 10-millimeter increase or more in Schirmer's tear test scores. This is in contrast to one of the other efficacy endpoint options listed by the FDA which includes pursuing not only at least one objective prespecified sign of dry eye but additionally requires at least one subjective prespecified symptom of dry eye.

Overall,tanfanercept was well tolerated and the safety findings from VELOS-3 were consistent with those of the previous studies without any significant new adverse events observed.

"The analyses of the Schirmer results for both phase III trials are highly encouraging for the impact it may have for dry eye disease patients and provides a compelling rationale for further development of tanfanercept. We would like to thank all the patients and healthcare professionals for their support and participation," stated Sean Jeong,M.D.,MBA,CEO of HanAll Biopharma. "HanAll intends to continue its evaluation of tanfanercept,and our future clinical program will build on the important learnings from the past three studies. Also,HanAll is exploring tanfanercept's further potential at higher concentrations as well as additional indications. We are planning the next study design within 2H2023 and intend to discuss the VELOS-3 data and future plans with the FDA at the earliest opportunity."

Thestudy data will be shared at upcoming scientific meetings.

HanAll Biopharma and Daewoong Pharmaceutical are co-developing tanfanercept therapies and hold global rights for tanfanercept except for within Mainland China,Hong Kong,and Taiwan.

Tanfanercept is a novel,potentially first-in-class topical anti-inflammatory treatment targeting tumor necrosis factor alpha (TNF-α) for the treatment of DED,co-developed with Daewoong Pharmaceutical. TNF is a major cytokine mediating inflammation in DED. Tanfanercept is a molecularly engineered tumor necrosis factor receptor 1 (TNFR1) fragment with strong affinity for TNF and resistance to degradation by proteinases.

VELOS-3 (NCT05109702) is a US-based multicenter,randomized,double-masked,vehicle-controlled Phase 3 study designed to evaluate the safety and efficacy of tanfanercept 0.25% for the treatment of adults with moderate to severe DED. The two primary outcome measures are change from baseline in Central Corneal Staining Score (CCSS) at 8 weeks and change from baseline in Eye Dryness Score (EDS) Assessed by Visual Analogue Scale at 8 weeks.

VELOS-2 (NCT03846453) is a US-based multicenter,vehicle- controlled Phase 3 study designed to evaluate the safety and efficacy of tanfanercept 0.25% for the treatment of adults with dry eye. The coprimary endpoints are change from baseline in inferior corneal fluorescein staining score to week 8 (Pre- to Post-Ora's CAE ®Dry Eye Challenge Model which utilizes a controlled adverse environment) andchange from baseline in ocular discomfort score to week 8 (Pre-CAE).

Dry eye disease is a chronic multifactorial disease characterized by ocular surface inflammation and damage,which can lead to visual impairment and symptoms significantly impacting quality of life (1,2). DED is a very common condition with prevalence estimation of 14.5% for the US population (3).

(1) Wolffsohn JS,Arita R,Chalmers R,Djalilian A,Dogru M,Dumbleton K,Gupta PK,Karpecki P,Lazreg S,Pult H,Sullivan BD,Tomlinson A,Tong L,Villani E,Yoon KC,Jones L,Craig JP. "TFOS DEWS II Diagnostic Methodology report." Ocular Surface. 2017 Jul; 15(3):539-574.

(2) Farrand,Kimberly F et al. "Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older." American journal of ophthalmology. 2017; vol. 182: 90-98.

(3) Paulsen AJ,Cruickshanks KJ,Fischer ME,et al. Dry eye in the Beaver Dam Offspring Study: Prevalence,Risk Factors,and Health-related Quality of Life. American Journal of Ophthalmology. 2014 Apr; 157(4):799-806.

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