Crescendo Biologics, based in Cambridge, UK, the drug discovery and developer of Humabody®-based therapeutics, and Takeda Pharmaceutical Company announced a global, strategic, multi- target collaboration and license agreement for the discovery, development and commercialization of Humabody® -based therapeutics for cancer indications with a high unmet medical need.

Crescendo’s Humabody® therapeutics are based on its proprietary, robust and highly efficient fully human VH domain technology platform (VH domains are only just a quarter of the size of Fab fragments). The company’s technology platform is centred on a unique and proprietary Triple Knock Out (TKO) transgenic mouse technology – the gold standard in antibody therapeutics development – in which all three endogenous antibody loci (heavy chain, κ light chain and λ light chain) are functionally silenced. This technology combines the benefits of producing a huge diversity of fully human VH domains (Humabody VH) in a background completely devoid of mouse antibodies with in vivo maturation and optimizes the affinity and biophysical properties of resulting monovalent VH building blocks and any configured mono- and multispecific Humabody therapeutics derived from them.


“… this collaboration is critical to helping us achieve our aspiration of curing cancer… and develop the next generation, highly modular and targeted therapies…”


Compared with monoclonal antibodies, Humabodies have differentiated pharmacological properties, offering a unique combination of potential benefits that results from their small size (e.g. 36 kDa for a trispecific Humabody), cost-effective production and modular plug & play engineering options for generating novel bi- or multi-specific formats.  Among the unique features is that Humabodies can rapidly penetrate and accumulate in tissue/tumours while clearing quickly from circulation to minimise systemic toxicity.

The unique properties of  Crescendo’s Humabody therapeutics, makes it possible to put them together in a rapid and highly flexible way, including site specific and homogenous drug conjugation. This, in turn,  offers increased specificity and superior toxicology profiles leading to an improved Therapeutic index (enabled by a “high dose, hit hard and leave” approach).

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Research
Earlier this year, during the 2nd Biologics and Biosimilars Congress in Berlin, Germany, Brian McGuinness PhD., MBA,  Crescendo’s Vice President of Discovery, presented data from a biosdistribution study confirming the rapid, homogeneous penetration and effective accumulation of Humabody constructs in a mouse xenograft tumour along with fast clearance of unbound material from systemic circulation. As a consequence, HDCs with highly potent payloads have the potential to generate a substantially superior therapeutic index to standard Antibody-drug Conjugates comprised of whole IgG.

Pipeline
Crescendo’s researchers have successfully demonstrated in vivo that Humabodies rapidly penetrate and accumulate within tumours resulting in a greatly increased tumour to blood ratio compared to IgGs. Based on these early results, Crescendo is building a pipeline of new differentiated medicines, including Humabody® Drug Conjugates, also known as HDCs, and multi-specific immuno-oncology (IO) modulators, through in-house development and strategic partnerships.

Agreement
Under the agreement with Takeda, Crescendo will use its proprietary transgenic platform and engineering expertise to discover and optimally configure Humabody® candidates (Humabody® Drug Conjugates and Immuno-Oncology modulators) against multiple targets selected by researchers at Takeda.

“We see significant potential in Crescendo and its innovative technology to develop unique, small and customizable Humabody®-based therapeutics,” said Andrew Plump M.D., Ph.D., Chief Medical and Scientific Officer, Takeda.

“Collaborations are critical to helping us achieve our aspiration of curing cancer. Working together with Crescendo will enable us to leverage its important technology to support Takeda’s goal of developing next generation, highly modular and targeted therapies to treat cancer,” Plump added.

Validation
“This collaboration with Takeda represents a significant step forward for Crescendo. It provides validation of our transgenic platform and our capabilities to rapidly assemble and configure small, differentiated Humabody®-based therapeutics, opening routes to novel biology,” noted Dr. Peter Pack, CEO, Crescendo Biologics.

“As a leading global pharmaceutical company, Takeda brings extraordinary expertise in the oncology area with significant capabilities in developing and delivering novel medicines to patients. This first major collaboration enables us to potentially broaden and accelerate innovative Humabody®-based product candidates,” he said.

Investment
Crescendo is eligible to receive up to $36 million, in a combination of an upfront payment, investment, research funding and preclinical milestones. Takeda will have the right to develop and commercialize Humabody®-based therapeutics resulting from the collaboration. Crescendo is also eligible to receive further clinical development, regulatory and sales-based milestone payments of up to $754 million. In addition, Crescendo will be eligible to receive royalties on Humabody®-based product sales by Takeda.

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