IGT-427, developed as MSD’s ‘MK-8748’ following acquisition of EyeBio
Four late-stage clinical trials for macular degeneration and macular edema; analysts estimate a total enrollment of approximately 4,000 patients
Combines vascular stabilization with VEGF inhibition to verify visual improvement and extended dosing intervals
The ophthalmic disease candidate 'IGT-427,' originally licensed out by Ingenia Therapeutics, is currently undergoing rigorous validation in large-scale global clinical trials conducted by Merck & Co. (MSD). The substance, which passed through the ophthalmology-focused biotech EyeBio before being integrated into MSD’s pipeline, is currently being developed under the designation 'MK-8748' as a treatment for neovascular age-related macular degeneration and diabetic macular edema.
MSD is conducting a total of four late-stage clinical trials. These include two Phase 2b/3 trials for neovascular age-related macular degeneration and two Phase 3 trials for diabetic macular edema. According to the U.S. clinical trial registry ClinicalTrials.gov, the combined enrollment target for these studies is 3,984 patients. This marks a significant milestone where a candidate licensed out by Ingenia during its pre-clinical stage has progressed through a global pharmaceutical company's development network to reach the stage of direct comparison with standard-of-care therapies.
The figure of approximately 4,000 patients represents the target enrollment, including control groups, and differs from the actual number of patients registered and treated.
From Pre-clinical Licensing to Global Late-Stage Trials
Ingenia was founded in Boston in 2018, leveraging foundational technologies from the Korea Advanced Institute of Science and Technology (KAIST) and the Institute for Basic Science (IBS). In 2022, the company licensed out the pre-clinical stage IGT-427 to EyeBio. Following MSD's acquisition of EyeBio in 2024, the candidate was incorporated into MSD’s ophthalmic pipeline.
MK-8748, also referred to as 'Tiespectus' or 'EYE201,' is a bispecific antibody that directly activates the TIE2 receptor while inhibiting vascular endothelial growth factor (VEGF). The development goal is to suppress pathological angiogenesis and leakage while enhancing vascular stability to reduce fluid accumulation in the macula.
Ingenia’s financial outlook is tied to its partner's development progress through milestone payments. On September 28, the company announced it would receive a $5 million milestone payment (approximately 6.8 billion KRW at the time of disclosure) following the initiation of the global Phase 3 trial for MK-8748 in diabetic macular edema.
This structure allows the original developer to benefit from the development capabilities of a global partner and share in the success without having to manage large-scale late-stage clinical trials directly.
Four Trials Across Two Indications: Direct Comparison with Standard Treatments
For neovascular (wet) age-related macular degeneration, Phase 2b/3 trials named 'MALBEC' and 'TORRONTES' are underway. For diabetic macular edema, Phase 3 trials named 'SANGIOVESE' and 'SYRAH' are being conducted.
According to data from ClinicalTrials.gov verified on November 10, the enrollment targets are 960 for MALBEC, 960 for TORRONTES, 960 for SANGIOVESE, and 1,104 for SYRAH. All four trials are currently listed as recruiting. The actual start date for the SANGIOVESE trial was August 27 of this year.
The core objective of these trials is to determine whether the new mechanism of action translates into actual therapeutic efficacy. The MALBEC trial compares two doses of MK-8748 against the standard-of-care, aflibercept 2mg. The primary endpoint is the change in best-corrected visual acuity at one year compared to baseline.
Dosing intervals are also a key point of interest. In the MALBEC trial, the MK-8748 group receives three initial doses at four-week intervals, followed by eight-week intervals until week 48, after which intervals are adjusted based on individual patient response. The aflibercept control group is designed to maintain eight-week intervals following initial doses.
The SANGIOVESE trial involves five initial doses at four-week intervals before transitioning to eight-week intervals. The MK-8748 group will have dosing intervals adjusted based on response after week 48, and long-term evaluation will include the proportion of patients treated at 8, 12, and 16-week intervals. This process aims to verify if visual acuity can be maintained or improved while reducing the frequency of injections.
Clinical Costs Estimated at Over 1 Trillion KRW by Securities Firms
The trillion-won figures appearing in reports related to Ingenia fall into three categories: the total value of the licensing agreement, the acquisition price paid by MSD for EyeBio, and estimates for late-stage clinical trial costs.
The 2022 licensing agreement with EyeBio, which included IGT-427, was reported to be worth over 1 trillion KRW. This represents the total potential value of the contract and does not equate to the cash Ingenia has received to date. It is necessary to distinguish between the candidates included in the contract, the scope of rights, and the milestone payments contingent upon future conditions.
The estimate of over 1 trillion KRW for clinical costs was provided by Shinhan Securities in September. This analysis covers the four late-stage clinical trials involving approximately 4,000 patients across two indications. However, the actual expenditure by MSD has not been confirmed.
The acquisition price for EyeBio is also separate. The transaction value announced by MSD totals up to $3 billion, consisting of a $1.3 billion upfront payment and up to $1.7 billion in contingent payments. As this was an acquisition to secure the company and its pipeline, it cannot be calculated solely as the development cost for the MK-8748 substance.
IGT-302 Glaucoma Option Terminated; Must Be Distinguished from MK-8748
There has been a recent change in the development path for another candidate. On the 9th, Ingenia announced that MSD decided not to exercise its option for the glaucoma indication of 'IGT-302.' The company received the relevant notice on the 7th.
This decision pertains to the glaucoma option under a separate research agreement signed in 2022. Ingenia is not required to return the $3 million in joint research and development funds already received. The company clarified that other ophthalmic licensing agreements remain valid. Ingenia plans to continue developing the glaucoma indication for IGT-302 independently. Therefore, this option termination should not be interpreted as a suspension of the late-stage trials for MK-8748 or a cancellation of the licensing agreement. The development paths and commercial potential of the two candidates must be evaluated separately.
The Next Hurdle: Visual Improvement, Safety, and Durability
The value of MK-8748 depends on the comparative clinical data to be secured in the future. The key factors are visual improvement compared to standard treatments, safety, retinal fluid control, and the potential for extended dosing intervals.
It is also necessary to distinguish these results from other MSD ophthalmic candidates. The results announced by MSD in the BRUNELLO trial pertain to data for 'remigromig (MK-3000),' a trispecific antibody that activates Wnt signaling. These are not the clinical results for the TIE2-activating and VEGF-inhibiting bispecific antibody, MK-8748.
The estimated primary completion date for the SANGIOVESE trial is October 2028, with the overall study completion expected in October 2029. These schedules are subject to change and do not represent approval or launch dates.
Ingenia has successfully connected an early-stage candidate to global late-stage clinical trials. The remaining challenge is to prove therapeutic efficacy, safety, and durability in large-scale comparative studies. The ability to achieve visual improvement comparable to existing treatments while reducing the burden of injections will be the benchmark for MK-8748's competitiveness.
