Amgen And Synaffix Alliance Could Be Biggest Preclinical ADC Licensing Deal Yet

Amgen has signed two big early-stage deals in a matter of days, signalling that antibody-drug conjugates are a priority target in oncology for the firm.

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Amgen has signaled its determination to be a major player in the increasingly competitive field of antibody-drug conjugates by signing a deal with Synaffix that could be the largest to date for a preclinical asset of this kind.

Antibody-drug conjugates (ADCs) have become one of the biggest growth classes in oncology in recent years, and one the biotech major wants to break into to expand its cancer drug portfolio.

The company is just one of many big biopharmas ramping up activity in order to follow in the footsteps of existing blockbusters in the field, including Roche’s Kadcyla (trastuzumab emtansine), Seagen/Takeda’s Adcetris (brentuximab vedotin). Most notable of all is AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan), for which consensus analyst forecasts now predict sales of more than $6bn by 2027.

Amgen will gain access to Synaffix’s next-generation ADC technologies for one program with the option to exercise exclusive research and commercial licenses for a further four programs at a later date.

Announcing the deal on 5 January, Synaffix did not provide details of any upfront payment, but said a deal signing fee, and milestones in the development of four candidates could reach up to $2bn, plus tiered royalties on potential future sales.

Peter van de Sande

Amgen coming on board adds to a string of deals signed by the Netherlands-based company, and its CEO Peter van de Sande told Scrip he believed it represented the biggest ever in-licensing of a preclinical ADC technology to date.

A research note from Capital One Securities last month recorded an “explosion” in the number of companies pursuing ADCs, which now number over 50. Deal-making in the arena has also seen huge growth in the last few years across in-licensing, IPOs and M&A deals, M&A and IPOs.

These have included Gilead’s $21bn buyout of Immunomedics in 2020,and in the same year, a second ADC in-licensing deal between AstraZeneca and Daiichi Sankyo. This was to develop the TROP2-targeted datopotamab deruxtecan and is worth  up to $6bn, and from which promising early data were recently released.  (Also see "AstraZeneca/Daiichi Sankyo’s Next ADC Shows Promise In Triple-Negative Breast Cancer" - Scrip, 9 Dec, 2022.)

Synaffix’s Next-Generation Platform

Van de Sande said the Amgen deal added to the validation of the company’s technologies, which aim to overcome limitations of existing ADC platforms, including issues around the stability of the construct, penetration of the tumor, release of the payload and serious toxicities.

These issues have held back the growth in the field to date, and safety and efficacy issues were behind GSK announcing the market withdrawal of its multiple myeloma ADC Blenrep (belantamab mafodotin) in November.  (Also see "Blenrep US Withdrawal Is A Big Blow To GSK’s Blockbuster Hopes" - Scrip, 22 Nov, 2022.)

Synaffix’s platform is built around three proprietary technologies, GlycoConnect, HydraSpace and toxSYN. Together these aim to improve how the cytotoxic agent is attached to the antibody, optimize tolerability, pharmacokinetics and manufacturability and allow faster development of new ADC candidates at licensing companies.

The new deal confirms that ADCs are a priority for Amgen, coming just days after a very similar in-licensing agreement with LegoChem announced on 27 December. This was based on the South Korea-based company’s ConjuAll ADC technology in up to five targets selected by Amgen, and worth up to $1.25bn including upfront, development and commercial milestone payments.

Also signing deals in December were Merck KGaA, via a pact with Mersana Therapeutics worth up to $830m, and Merck & Co. and Kelun-Biotech, in a deal which could hit a maximum value of $9.3bn, based on seven preclinical ADC candidates.

The Amgen deal represents Synaffix’s twelfth licensing deal, with existing partners including ADC Therapeutics, Mersana Therapeutics, Inc., Innovent, Kyowa Kirin and Genmab.

Van de Sande told Scrip much of its newly increased revenue stream would be invested into scaling up its manufacturing capacity to meet the demand from the growing number of its partnered molecules in clinical development.