Dresden biotech Seamless lands up to $1.1B Eli Lilly deal for gene therapy hearing loss

The Dresden biotech company Seamless Therapeutics GmbH (with its US Inc. subsidiary based in the Boston area) has signed a worldwide strategic research and licensing agreement with Eli Lilly and Company. The aim of the collaboration is the development and subsequent commercialisation of programmable, recombinase-based gene therapies for selected forms of genetically caused hearing loss.

As part of the collaboration, Seamless contributes its proprietary recombinase platform, which enables precise and large-scale DNA insertions and modifications independently of cellular DNA repair mechanisms. This is the key differentiator of the editing method devised by Prof Frank Buchholz at the Medical Faculty of TU Dresden compared with the more widely used CRISPR/Cas technology. Lilly brings its extensive development and clinical expertise in genetic hearing disorders, while Seamless focuses on identifying and designing the appropriate recombinase for the targeted DNA sequence.

Within the project, Seamless will develop tailored, site-specific recombinases designed to correct disease-causing mutations in selected target genes. Owing to the multiple activity centres of recombinases, both cutting and the insertion of very long DNA fragments can be achieved with high precision. Although the platform is still at an early preclinical stage, Eli Lilly is entering the collaboration with a substantial deal volume and, in return, receives an exclusive licence in the hearing loss field to advance the candidates preclinically and clinically and to commercialise them.

A platform in the shop window for further partners

Albert Seymour, CEO of Seamless Therapeutics, emphasised the strategic importance of the collaboration and the validation of the company’s technology platform. “Lilly is invested in advancing novel treatment approaches for genetic diseases and shares our vision of bringing genetic medicines to patients who currently have limited treatment options. This collaboration is a validation of our gene editing platform and its broad disease-modifying potential.”

Financially, the agreement includes a guaranteed upfront payment as well as committed research and development funding. In total, Seamless may receive payments of up to USD 1.1 billion, including development and commercial milestone payments. Tiered, sales-based royalties are not included. Further details of the agreement have not been disclosed.

Speaking to European Biotech News, Seymour added: “Our task is to identify and nominate the most suitable recombinase from several developed candidates for further development by Lilly. Lilly contributes the expertise in the genetics of hearing loss. This model also lends itself to further collaborations that fit our corporate strategy.”

Directed evolution delivers tools of choice

Recombinases have been used in basic research for decades. Seamless Therapeutics has, however, further developed and programmed this enzyme class to enable highly precise genetic changes such as the insertion, exchange or removal of DNA sequences at defined genomic loci. “What convinced Lilly was that we were able to present data from animal studies,” Seymour commented. “We are now truly at the point where we are moving beyond platform development and heading decisively towards the clinic.”

Seymour is primarily based in a suburb of Boston and has long been familiar with the US East Coast biotech scene. He sees Seamless as distinctly positioned compared with many other companies in the CRISPR field or broader gene therapy approaches. “With our ability to design recombinases for specific sequences and the various options a recombinase offers beyond cutting, we have opened up an entirely new field.”

Seamless does not intend to remain solely a service provider and development partner for the pharmaceutical industry, despite growing interest. The Dresden-based company also aims to advance its own recombinase programme as far as possible in a self-selected indication. Data and details on the exact target are expected to be presented later this year. With its ‘recombinase on demand’, Dresden has secured a place in the spotlight of the gene editing scene.

Interest in genetically caused hearing loss is also reflected in a recent deal between Sanofi and the French company Sensorion (Marseille), which simultaneously announced a EUR 60 million financing to advance another of its gene therapy programmes into the clinic (another asset from Sensorion using a different approach is also already in clinical development).