AbbVie goes preclinical in pursuit of cancer payoff

Since AbbVie has not been able to acquire its way out of a looming Humira patent mess, it seems to be trying to license its way out. The Illinois-based group splashed out a total of $70m yesterday on two preclinical oncology projects aimed at novel cellular targets.

The deals with Argen-X and CytomX Therapeutics mark the fourth and fifth projects AbbVie has licensed in this year, for a disclosed total of $665m in immediate cash payments. Having partnered with Boehringer Ingelheim to shore up its autoimmune pipeline, AbbVie has now turned to cancer (Next-generation psoriasis battle lures AbbVie, March 8, 2016).

AbbVie paid Netherlands-based Argen-X $40m up front for an option to license ARGX-115, an antibody acting on a checkpoint inhibitor called GARP (glycoprotein A repetitions predominant), a protein that modulates the activity of regulatory T cells that suppress anti-tumour immune response.

Hours later, the big pharma group also announced a $30m deal to collaborate on California-based CytmoX’s antibody-drug conjugate that specifically targets the cellular receptor CD71.

Imbruvica and then some

Yesterday’s deal-making follows some aggressive moves into oncology. Until last year AbbVie recorded less than $1bn a year in oncology sales, but the acquisition of Pharmacyclics brought half of the economic interest of the blockbuster Imbruvica, and the approved drug Venclexta and phase III project veliparib promise to add $3bn to the top line by 2022, according to EvaluatePharma’s consensus.

Much of its late stage pipeline consists of small molecules. Thus a move into biologicals and immuno-oncology signals that AbbVie wants to diversify and is thinking past 2020, when top-seller Humira will be facing increased competition from biosimilars. Furthermore, it has bypassed well-advanced targets like PD-1, where agents like Bristol-Myers Squibb’s Opdivo and Merck & Co’s Keytruda have gobbled up market share.

The deal with Argen-X will see the Netherlands company take responsibility for preclinical development through the necessary studies to file a US IND. At that point AbbVie may exercise its option to license the candidate and assume responsibility for clinical and commercial development. AbbVie could pay up to $645m in milestones, with sales royalties and European co-promotion rights possible after launch.

More precision

CytomX’s antibody-drug conjugate, meanwhile, represents a slightly less novel approach but adds refinements that aim to reduce off-target effects. The mechanism is CD71, or transferrin receptor1, a protein that has a function in cellular iron uptake and is more active in tumour cells.

The AbbVie-partnered project, which CytomX calls “probodies”, adds a refinement to standard antibody-drug conjugates, and uses a peptide that renders the protein inert until activated by proteases in the tumour. This aims to prevent binding to healthy tissue, which in theory should help to limit side effects as well as allowing more highly cytotoxic payloads to be delivered to tumour cells.

In exchange for AbbVie’s $30m payment CytomX will lead preclinical and early clinical development, with the two parties jointly sharing global late-stage development costs. Milestones of $470m are possible, along with profit sharing on US sales and royalties elsewhere.

In spite of the threat to its biggest-selling drug AbbVie has remained committed to the space it is in, autoimmune disease – however, it probably sees how biosimilars and new competitors will encroach on its leading position. Broadening its position in oncology, and in doing so attempting to leapfrog dominant players like Roche, Bristol-Myers, and Merck, seems to be a canny move.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @ByJonGardner on Twitter

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