Belite Bio (NASDAQ:BLTE) executives outlined the scientific, regulatory and commercial rationale for tinlarebant, the company’s lead oral therapy for retinal diseases, during a Goldman Sachs discussion focused on Stargardt disease and geographic atrophy.
Hendrik Scholl, chief medical officer of Belite Bio, said tinlarebant, also known as LBS-008, is designed to reduce vitamin A delivery to photoreceptors by antagonizing RBP4. The company has initiated a rolling New Drug Application submission for Stargardt disease.
Company Highlights RBP4 Approach
In Stargardt disease, Scholl said the condition is monogenic and caused by mutations in the ABCA4 gene, which plays a role in the visual cycle. Dysfunction in ABCA4 can lead to accumulation of all-trans retinal and formation of toxic deposits such as A2E in the retinal pigment epithelium.
Scholl emphasized that tinlarebant is not a visual cycle modulator. Instead, he said it aims to reduce vitamin A in photoreceptors by lowering the substrate available for toxic deposit formation.
“Tinlarebant allows to very precisely, almost with the precision of gene therapy because of the RBP4 receptor, to reduce the content of vitamin A in the photoreceptors and therefore reduce toxicity in the eye without having any safety concern for any other organ,” Scholl said.
DRAGON Trial Data Support NDA Filing
Discussing the company’s regulatory strategy, Scholl said the primary endpoint in Stargardt disease was informed by ProgStar, a large natural history study he previously led. He said ProgStar helped establish definitely decreased autofluorescence, or DDAF, as a measurable lesion endpoint that enlarges at a predictable rate and correlates with long-term visual function.
Scholl said visual acuity is a difficult endpoint in Stargardt disease because average visual acuity loss is slow, at about half a letter per year, with significant intersession variability.
In the DRAGON trial, Belite Bio used DDAF as the primary endpoint. Scholl said patients receiving 5 milligrams per day of tinlarebant had a progression rate of 0.38 square millimeters per year, compared with 0.59 square millimeters per year in the placebo group. He said the result was statistically significant, with a pre-specified p-value of 0.0033 using an unstructured covariance matrix and a p-value of less than 0.0001 using an autoregressive model covariance structure.
Scholl also said the key secondary endpoint, decreased autofluorescence, showed a statistically significant treatment effect.
On safety, Scholl said the trial included 104 Stargardt subjects over two years and recorded six serious adverse events, four in the placebo group and two in the treatment group. He said none were related to treatment, and ocular adverse events were mostly mild, mechanism-related and generally resolved while patients remained on therapy.
Potential Label and DRAGON II
Scholl said the company believes a single DRAGON trial can support its FDA application. He added that DRAGON II was originally designed to meet requirements in Japan and collect data in Japanese patients, who could not participate in the first DRAGON trial.
“The DRAGON II trial is not intended as a second trial to support our submission to the FDA,” Scholl said, adding that it could potentially support the application if needed as a post-marketing commitment.
On labeling, Scholl said Belite Bio has discussed with the FDA an intended designation for patients 12 years and older. He said Stargardt disease is the same disease regardless of age of onset because it is driven by ABCA4 dysfunction. In his view, tinlarebant could be relevant across a broad range of Stargardt patients, including those earlier in disease and those with advanced vision loss.
Commercial Planning and Patient Population
Scholl said recent genetic database research has improved estimates of the Stargardt patient population. He cited an estimated 49,000 to 57,000 Stargardt patients in the United States across all ages, races and diagnosis status.
He said many patients likely carry some diagnosis because Stargardt is severe, but genetic confirmation remains a hurdle. Scholl said he believes genetic confirmation should be part of the standard of care and that Belite Bio is working to increase genetic testing ahead of launch.
The Operator said existing labs provide testing, including one fully sponsored by the Foundation Fighting Blindness, and that insurance covers much of the cost in many cases. The Operator said Belite Bio’s pre-approval efforts are focused on disease awareness and education about available testing.
The Operator also said the company has conducted pricing research, patient journey research and database analysis to estimate how many U.S. patients are already diagnosed and genetically confirmed. Belite Bio plans to hold a commercial day event in September to share more information, according to the Operator.
Cash Position, PRV and Pipeline Expansion
The Operator said Belite Bio believes it can launch tinlarebant for Stargardt disease in the United States because the disease is rare and the company has experience in inherited retinal disease. The Operator said the company has $800 million in cash, with an estimated U.S. commercialization budget of about $300 million and pipeline costs of roughly $150 million over the next three years.
“With $800 million cash, we think we are pretty comfortable that we should be able to launch this in the U.S.,” the Operator said.
The Operator also said Belite Bio may qualify for a priority review voucher if tinlarebant is approved under its rare pediatric disease designation. The earlier cash planning did not include a potential $100 million to $200 million in proceeds from a voucher, the Operator said.
Looking beyond Stargardt and geographic atrophy, the Operator said the company may consider expanding into other inherited retinal diseases if revenue from Stargardt supports further development.
About Belite Bio (NASDAQ:BLTE)
Belite Bio, Inc (NASDAQ: BLTE) is a clinical-stage biotechnology company focused on discovering and developing small molecule therapeutics for metabolic and inflammatory diseases. Leveraging a proprietary drug-discovery platform, the company aims to address conditions such as nonalcoholic steatohepatitis (NASH) and obesity by targeting pathways involved in fibrosis, inflammation and metabolic regulation.
Belite Bio’s pipeline includes multiple candidates in preclinical and early clinical development stages.
