Ocugen says it is on track to reshape the market for gene therapies against eye disorders over the next three years, by working to bring to market three treatments for blindness-related diseases, two of them now in late-stage trials.
Furthest in the clinic is Ocugen’s OCU400 modifier gene therapy, designed to treat early to advanced cases of retinitis pigmentosa (RP), including clinical and/or genetic diagnosis with both syndromic and non-syndromic forms of the disease.
Ocugen hopes to succeed where Spark Therapeutics and parent company Roche failed in recent years, namely, establishing a commercially successful adeno-associated virus (AAV) gene therapy franchise for an eye disorder through its pioneering gene therapy Luxturna® (voretigene neparvovec-rzyl), which made history in 2017 as the first FDA-approved gene therapy for an inherited disease. Two years later, Roche acquired Spark.
To that end, Ocugen says it is actively recruiting patients ages 5 and older in the United States and Canada for its Phase III liMeliGhT trial (NCT06388200) and expects to complete enrollment in time to generate the data it will need to support an FDA biologics license application (BLA) as well as a marketing authorization application (MAA) with the European Medicines Agency, both expected in 2026. The liMeliGhT trial focuses on RP associated with rhodopsin (RHO) mutations, as well as any other RP associated mutation with a clinical phenotype of RP.
Shankar Musunuri, PhD, Ocugen’s chairman, CEO, and co-founder, told GEN Edge, Ocugen’s treatments represent an advance over traditional gene therapies aimed at a single gene. Since RP is linked to more than 200 RHO mutations in more than 100 genes, he noted, “you would need 100 traditional gene therapy products, and so that’s impossible for biotechs and pharma companies.”
“Some people take XLRP [X-linked retinitis pigmentosa] because that’s 5% to 10% of the RP population,” Musunuri said. A study published January 7 in Nature Eye cited a 5% to 15% range for XLRP. Musunuri added: “Okay, they have a few thousand patients at least. Commercially, it’s meaningful. But a lot of patients will still be left out.” Ocugen estimates that 300,000 people in the United States and Europe have RP.
“Significant impact globally”
“With our therapy, we can target the entire population with RP, and we can have a significant impact globally,” Musunuri asserted.
Due to its novel gene-agnostic mechanism for action, OCU400 has the potential to address more than 100 different mutations associated with RP, Musunuri told analysts on Ocugen’s second-quarter earnings call.
By contrast, Luxturna is indicated to treat retinal dystrophy associated with mutations in both copies of a single gene, retinal pigment epithelium-specific 65 kDa protein (RPE65). Patients must have an inherited retinal disease such as RP or Leber congenital amaurosis (LCA), and enough viable retinal cells as determined by a physician.
“When you have any defect, what we found is that key functioning genes like the transcription factors responsible for cell development, metabolism, inflammation, phototransduction, and cell survival, they’re all depressed. And we found a missing link in RP: It’s a modifier gene, NR2E3, that’s depressed,” Musunuri explained.
NR2E3—which stands for nuclear receptor subfamily 2, group E, member 3—regulates diverse physiological functions within the retina. “When you upregulate NR2E3 through AAV, it regulates all these key functioning genes, restores their function, resets the homeostasis, and also creates a healthy environment for these retinal cells to survive. Because of that concept, we can go after the disease,” Musunuri added. “We don’t go after one gene at a time or one mutation at a time as in gene editing.”
Improving commercial viability
Going after multiple genes expands the treatment population, thus improving the potential commercial viability of OCU400, Ocugen reasons.
According to Roche, Luxturna generated CHF 18 million ($22.3 million) in sales during 2024, compared with about CHF 46 million ($56.9 million) in 2023—both far short of peak sales forecasts ranging from $350 million to $750 million by 2022, and total lifetime revenues of $1 billion–$3 billion when the therapy was approved.
An article published by healthcare consultancy Recon Strategy found Luxturna to be commercially hamstrung in part by overestimates of its patient population, which at about 650 fell short of estimates of 1,000 to 2,000 patients in the United States with biallelic RPE65-associated retinal dystrophy. Another factor blamed for slow sales has been Luxturna’s list price of $425,000 per eye.
Roche has completely written off Spark, recording a full impairment of CHF 2.122 billion ($2.624 billion) as goodwill from its $4.3 billion acquisition of Spark, completed in 2019 (and lowered from the initial $4.8 billion price when $500 million in projected net cash didn’t materialize as expected).
Ocugen is also studying OCU400 as a treatment for LCA with CEP290 mutation in a Phase I/II trial (NCT05203939). OCU400 has received the FDA’s Regenerative Medicine Advanced Therapy (RMAT) and orphan drug designations, as well as the European Medicines Agency’s Orphan Medicinal Product Designation (OMPD) and Advanced Therapy Medicinal Product (ATMP) classification.
Targeting RORA
While OCU400 is planned for a BLA next year, Ocugen hopes in 2027 to pursue the same path for OCU410ST, a treatment for Stargardt disease (ABCA4–associated retinopathies) that uses AAV5 for the retinal delivery of the RORA (RAR-Related Orphan Receptor A) gene.
Last month, Ocugen dosed the first patient in its Phase II/III GARDian3 trial (NCT05956626), which is set to enroll 51 participants diagnosed with Stargardt, of which 34 will receive a one-time subretinal injection of OCU410ST (200 μL at 1.5 × 10¹¹ vector genomes/mL) in the eye with poorer visual acuity, while 17 will be assigned to an untreated control group. The trial’s primary endpoint is reduction in atrophic lesion size, while key secondary endpoints include improvements in best corrected visual acuity (BCVA) and low luminance visual acuity (LLVA), compared to controls.
OCU410ST in May received the FDA’s Rare Pediatric Disease Designation for the treatment of ABCA4-associated retinopathies, including Stargardt disease, retinitis pigmentosa 19, and cone-rod dystrophy 3. OCU410ST previously received orphan drug designations for the treatment of ABCA4-associated retinopathies from the FDA and European Medicines Agency. According to Ocugen, Stargardt has an estimated patient population of approximately 100,000 people.
Ocugen’s third planned BLA, set for 2028, would be for OCU410, a multifunctional modifier gene therapy designed to target multiple pathways in order to treat geographic atrophy (GA), an advanced stage of dry age-related macular degeneration (dAMD) with a patient population estimated by Ocugen at between 2 to 3 million people. Like OCU410ST, OCU410 uses AAV for retinal delivery of the RORA gene.
“Disease progression targets key pathways like oxidative stress, lipid metabolism, inflammation, and the complement system—the same pathways degenerate in dAMD as in Stargardt, so both can be treated by a modifier of RORA. It regulates all these pathways and also creates a healthy environment for photoreceptors and RPE cells to survive, and that’s a very powerful concept,” Musunuri said.
OCU410 is now under study in the Phase I/II ArMaDa trial (NCT06018558), which in February completed patient dosing in the Phase II portion, with 51 participants randomized into treatment and control arms. OCU410 I set to enter Phase III trials in 2026.
GA has seen two new high-profile treatments enter the market in recent years—Apellis Pharmaceuticals’ Syfovre® (pegcetacoplan injection) and Astellas Pharma’s Izervay
(avacincaptad pegol intravitreal solution). Both have benefited from saturation advertising campaigns; Syfovre through ads featuring Henry Winkler, who played Fonzie in the 1970s sitcom “Happy Days,” while Izervay uses a jingle based on War’s 1975 hit song “Low Rider.”
Izervay and Syfovre both target the complement system, with Izervay inhibiting C5 and Syfovre, C3. “The core to this disease is really focused on oxidative stress and lipid metabolism. So all these pathways, RORA regulates, and also creates the same healthy environment for photoreceptors and RPE cells to survive. That’s an important difference,” Musunuri said.
Other differences: Syfovre and Izervay require monthly or bimonthly injections (every 25–60 days for Syfovre; approximately 28 +/- 7 days for Izervay), while OCU410 is a one-time treatment.
Modifier gene therapy platform
Like OCU400, OCU410 and OCU410ST apply Ocugen’s modifier gene therapy platform. The platform is based on the use of nuclear hormone receptors (NHRs), which, according to the company, have the potential to achieve homeostasis. Using NHRs allows the platform to apply a gene-agnostic approach designed to address not just the mutated gene but also provide a molecular reset of health and survival of gene networks.
“We’re very enthusiastic about the progress of our novel modified gene therapy platform,” Musunuri said. “We remain steadfast in our mission to provide a one-time therapy for life to address considerable unmet medical needs that exist for millions of patients facing the terrifying prospect of losing their vision.”
Ocugen is counting on its modifier platform to catapult it well past the 50 cents-to-$1.40 stock price range where it has hovered over the past 52 weeks. Ocugen shares are up 33% over the past six months, having climbed from 75 cents on February 5 to an even $1 at Monday’s close.
Daniil Gataulin, PhD, a senior research analyst at Chardan covering biotech companies with a focus on ophthalmology, reiterated his firm’s “Buy” rating and 12-month price target of $7 per share on Ocugen stock set on June 24—the same day Swayampakula Ramakanth, PhD, a managing director and senior healthcare analyst with H.C. Wainwright, reiterated his firm’s “Buy” rating and $7 price target.
Ocugen finished the second quarter with a net loss of $14.739 million, compared with a $15.28 million net loss a year earlier. During the first half of 2025, Ocugen’s net loss grew nearly 11% year-over-year, to $30.089 million from 27.204 million. Revenue, generated entirely from collaborations, rose 20% in Q2 to $1.373 million from $1.141 million the previous year, while six-month revenue jumped 32% to $2.854 million from $2.155 million in January–June 2024.
The Q2 loss rose to $370.3 million, Ocugen’s accumulated deficit, while the company’s available cash, cash equivalents, and restricted cash shrank about 54% from Q1, from $58.8 million to $27.3 million. “This amount will not be sufficient to fund the company’s operations over the next 12 months after the date that the condensed consolidated financial statements are issued,” Ocugen acknowledged in its most recent Form 10-Q quarterly regulatory filing.
As a result, Ocugen said, it is exploring options for funding its operations that include:
- Public and private placements of equity and/or debt
- Payments from potential strategic research and development arrangements
- Sales of assets
- Licensing and/or collaboration arrangements with pharmaceutical companies or other institutions
- Government funding, “particularly for the development of the company’s novel inhaled mucosal vaccine platform”
- Funding from other third parties
“Going Concern” Language
“While management believes that we have a plan to fund operations, our plan may not be successfully implemented. If we cannot obtain the necessary funding, we will need to delay, scale back, or eliminate some or all of our research and development programs and commercialization efforts; consider other various strategic alternatives, including a merger or sale; or cease operations,” Ocugen cautioned in its 10-Q filing.
“As a result of these factors, together with the anticipated continued spending that will be necessary to continue to research, develop, and commercialize our product candidates, there is substantial doubt about our ability to continue as a going concern within one year,” the company added, using “going concern” language similar to that found in its quarterly and annual filings stretching back to the second quarter of 2017, two years before the former Histogenics took its current name after completing a reverse merger with Ocugen Opco.
In June, Ocugen announced one effort aimed at generating capital—an all-stock reverse merger of its OrthoCellix subsidiary focused on developing regenerative cell therapies for orthopedic diseases with publicly-traded Carisma Therapeutics. The combined company would aim to develop OrthoCellix’s NeoCart® technology for the treatment of knee articular cartilage defects, with plans to gain FDA approval to launch a Phase III trial.
“It’s a platform technology. It doesn’t have to stop with cartilage repairs. It can go to shoulder surgeries,” Musunuri said. “Also, there’s a technology in the IP which can also go into spinal cord and other orthopedic diseases. This is going to be a regenerative cell therapy focused on orthopedic diseases.”
Upon closing of the deal and an anticipated $25 million concurrent financing, Ocugen and other financing participants are expected to own about 90% of the combined company, with existing Carisma stockholders to own the remainder, each on a fully diluted basis.
Phase III plan
Once the deal is completed, how soon can Ocugen launch Phase III studies of NeoCart?
“Within 3 to 6 months, we can start the Phase III, and it’s a two-year duration. That’s the plan,” Musunuri said. The trial’s comparator arm would be debridement through chondroplasty. NeoCart has received the FDA’s RMAT designation, potentially allowing for accelerated development and review that could enable a launch in 2029.
Another potentially lucrative cash-generating avenue for Ocugen is its business development effort to pursue regional development partnerships for OCU400. Ocugen reasons that a region-by-region approach will enable it to maximize patient reach while preserving its rights to therapies in larger geographies. The regional deals also fit with one of Ocugen’s goals, to “improve health and offer hope for patients across the globe.”
In June, Ocugen signed a binding term sheet to negotiate and enter into a licensing agreement for exclusive South Korean rights to OCU400 with an undisclosed “well-established leader in the pharmaceutical and healthcare sector in Korea.”
Under the term sheet, Ocugen says, it would receive upfront license fees and near-term development milestones totaling up to $11 million, plus sales milestone payments estimated to total $150 million or more in first 10 years of commercialization—based on $1 million for every $15 million of net sales in South Korea, plus a 25% royalty on net sales of OCU400 generated by Ocugen’s partner. Ocugen will manufacture commercial supply of OCU400 under a supply agreement.
“We’re working with a number of opportunities. And this one materialized first. We are hopeful to close that agreement by the end of summer,” Musunuri said. “Picking up regional players to have good access in those markets is really important for Ocugen and for our patients. That sets up a good metric for us, and we’ll continue to do those regional deals, at the same time making sure we have our revenue for the United States and major markets so that our shareholders are happy.”
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