Half-life extension for biologics against retinopathies

Retinopathies, including age-related macular degeneration (AMD) and diabetic retinopathy (DR), are among the major causes for impaired vision and eventual blindness. Globally, more than 190 million individuals are affected by AMD and 93 million people are suffering with diabetic retinopathy.^1,2 Retinopathies are characterized by damage to the retina which can stem from several different causes including damage to blood vessels or macular cells.

Intravitreal drug delivery is the preferred route of administration for biologics intended to treat these retinopathies³. However, injection into the eye is associated with the risk of intraocular infection or inflammation and represents a high burden for the patient. Thus, injection frequency is of great importance.  In order to ease this burden, our aim is to increase the time interval between two injections, i.e., to decrease injection frequency.

The vitreal half-life determines the injection frequency and it is known that the size of a molecule is a key parameter for the vitreal half-life. Larger molecules, which diffuse more slowly through the vitreous body, are known to have longer vitreal half-lives than smaller molecules.

While a large size can increase the half-life in the vitreous, it can also restrict penetration into tissues.  Penetration into the retina is required for most therapeutics to reach their site of action (target). Molecule size may hinder drug candidates from penetrating through the inner limiting membrane into the retina and further into deeper layers of the retina. 

However, optimization of the molecular size is limited and therefore additional mechanisms for extending the half-life are required. The challenge is to find alternative approaches, e. g. new types of biotherapeutics, extending the vitreal half-life of proteins on the one hand and allowing the drug to penetrate well into the retina on the other hand.

To identify a new approach, many molecules will need to be screened to identify optimal properties. To screen these molecules, one important requirement is to develop in vitro or ex vivo assays that are predictive for vitreal half-life and retinal penetration. In vivo testing is not feasible for a large number of drug candidates, and so relying on in vivo proof of concept alone will not allow for successful candidate progression.

Therefore, as part of this opn2EXPERTS question two related, but independent solution approaches are in scope:

First, we are looking for novel biotherapeutics approaches to enable both intravitreal half-life extension and increased retinal penetration of biotherapeutic molecules. Secondly, we are seeking innovative functional assay models to assess and validate the half-life extension and retinal penetration of biologics. Proposals that address either one of these two or both objectives would be in scope and eligible for a scientific review through our expert jury.

1. Any novel, molecular approach that extends the vitreal half-life and increases retinal penetration of biologics. Covering, but not limited to the following ideas
   • Novel types of antibody/protein fusions (molecular formats)
   • Antibodies/binders to antigens facilitating ivt half-life extension or retinal penetration
   • Chemical modification of biologics, etc.
2. In addition, any innovative functional approach that allows analyzing intravitreal half-life extension and retinal penetration of biotherapeutic molecules, such as
   • Predictive in vitro and ex vivo assay systems or multi-cellular or 3D tissue based assays, or
   • biomechanical systems.
3. Suggested models need to have conceptual link to treat human retinopathies.

The following will be considered out of scope:

• Conventional approaches to extend half-life and retinal penetration of biologics that are based on pegylation or similar technologies.
• Proposals focusing exclusively on device technologies
• Proposals that focus exclusively on formulation approaches
• Proposals that represent in vivo models, assays, or methods suited solely for small molecules
• Proposals focusing on gene therapies

If your project is selected, you will have the opportunity to directly collaborate with the Biotherapeutics Discovery and Retinopathy Research teams of Boehringer Ingelheim and tap into their experience in the fields of biologics molecule discovery, biologics engineering, retinopathies, pharmacokinetics and -dynamics. In addition, you can expect appropriate funding for the prospective collaboration period. Your exact funding request should be outlined in your proposal. As a framework, we suggest that your initial funding request is structured in milestone and does not exceed 200,000 euros per submitted project in total.

Our collaboration agreement will provide full transparency about each partner’s rights & obligations (including intellectual property rights). As part of the agreement, you will be encouraged to publish following the collaboration agreement (to be negotiated in good faith).

To maintain the highest degree possible in an open innovation environment, we plan to announce the winner(s) publicly and feature them on opnMe.com and our social media channels.

We are seeking research collaboration proposals that contain:

• A well-structured proposal outlining a new and compelling scientific approach.
• Outlining of the technical feasibility, and potentially existing data or previous publications that support feasibility / experience with outlined technology, based on existing techniques and established assays.
• Your exact funding request should be outlined in your proposal based on a well-thought-through project. The project should be structured in milestones and planned with key decision points (clear Go/No-Go criteria). The funding request for the initial milestones resulting in a Go/No-Go decision should not exceed 200,000 euros per submitted project in total.
• Proven track record in the required field of expertise.
• Ability to implement the outlined solution as part of a scientific collaboration project with Boehringer Ingelheim including access to a laboratory.

Please use our answer submission template to provide a 2-3 page non-confidential proposal (available for download here).

If confidential data exists that would strengthen the proposal, please indicate that information is available to share under a Confidential Disclosure Agreement (CDA). If we find the non-confidential concept proposal sufficiently interesting, we will execute a CDA for confidential discussions.

We have been looking for answers for the following scientific challenge: Using novel types of biotherapeutics or functional assays, how would you propose to extend or validate the intravitreal half-life and retinal penetration of biologics?

All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial funding of up to 200,000 euros will be available for each selected proposal.

We can only accept research proposals if they arrive by the submission deadline on November 07, 2022, 11.59 pm PST.