Seattle Genetics

Collaboration Agreements

Seattle Genetics has collaboration agreements with Takeda Oncology Company (formerly Millennium) to develop and commercialize brentuximab vedotin. The company also has collaboration agreements for their ADC technology with a number of biotechnology and pharmaceutical companies, including, AbbVie, Bayer Celldex Therapeutics, Inc., Daiichi Sankyo, Genentech, Inc., GlaxoSmithKline, Pfizer, Inc. and PSMA Development Company LLC as well as ADC co-development agreements with Agensys, Inc., an affiliate of Astellas Pharma and Oxford BioTherapeutics Ltd.

MMAE-based

Seattle Genetics' proprietary Monomethyl auristatin E or MMAE-based antibody-drug conjugate technology, employed in brentuximab vedotin, empowers monoclonal antibodies to treat cancer. Brentuximab vedotin, for example, links the chimeric anti-CD30 monoclonal antibody (cAC10) via a protease-cleavable linker to MMAE. This ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells. This approach is intended to spare non-targeted (healthy) cells and thus reduce many of the toxic effects of traditional chemotherapy while potentially enhancing antitumor activity. (See also vedotins)

PBD based

Seattle Genetics is also evaluating another ADC technology using a highly potent cytotoxic agent called a pyrrolobenzodiazepine (PBD) dimer that kills cells by a different mechanism than auristatins (monomethyl auristatin E or monomethyl auristatin F). Pyrrolobenzodiazepine (PBD) dimer is currently employed in SGN-CD33A and SGN-CD70A. It is stably linked to an antibody with Seattle Genetics' site-specific engineered cysteines, resulting in uniform drug-loading of two PBD dimers per antibody.

Early years

Seattle Genetics was founded in 1997 and is headquartered in Bothell, Washington, a suburb of Seattle. The company completed an initial public offering in March 2001, and is traded on the Nasdaq Stock Market under the symbol SGEN. To date, the company has more than 650 employees throughout the United States.

2009

19 February — pivotal trial for Brentuximab vedotin for Hodgkin lymphoma 18 June — phase II trial of Brentuximab vedotin for Anaplastic large cell lymphoma 24 July — initiation of re-treatment clinical trial of Brentuximab vedotin 10 August — milestone achievement in collaboration with MedImmune through initiation of phase I clinical trial of MEDI-547. 8 September — milestone achievement in collaboration with Bayer for the submission of investigational new drug application with the FDA 5 October — discontinuation of Phase IIb trial with Dazcetuzumab (also known as SGN-40 or huS2C6) for the treatment of diffuse Large B-cell lymphoma 16 November — initiation of phase I clinical trial for SGN-75 (INN: vorsetuzumab mafodotin) 11 December — termination of collaboration with Genentech for SGN-40 21 December — announcement of new collaboration with GlaxoSmithKline ($12 million up front payment, up to $390 million in milestone payments)

2010

2 February — initiation of phase I combination clinical trial of Brentuximab vedotin (SGN-35) for Hodgkin Lymphoma 3 March — milestone achievement under collaboration with Genentech 8 April — initiation of phase III trial for Brentuximab vedotin (SGN-35) for post transplant Hodgkin Lymphoma 20 April — $9.5 million payment from Genentech to extend collaboration 20 July — initiation of phase I clinical trial of ASG-5ME for treatment of Pancreatic cancer 3 August — expansion of collaboration with Genentech ($12 million ufront payment, up to $900 million in potential fees and milestone payments) 2 September — milestone achievement in collaboration with Agensys for initiation of phase I trial of AGS-16M8F 14 September — entry into collaboration with Genmab 20 October — initiation of phase I clinical tria; of ASG-5ME in prostate cancer treatment

2011

6 January — entry into collaboration with Pfizer ($8 million upfront payment, $200+ million in potential milestone payments) 1 March — initiation of phase I clinical trial of Brentuximab vedotin for use in conjunction with chemotherapy for treatment of systemic anaplastic large cell lymphoma 15 March — expansion of collaboration with the Millennium Pharmaceuticals (Takeda Oncology) 22 March — announcement of collaboration with Abbott ($8 million upfront payment, plus potential royalties and milestone payments) 19 April — expansion of collaboration with Genmab 19 August accelerated FDA approval for Brentuximab vedotin for use in treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL) 23 August — initiation of phase II trial of ADCETRIS in CD30-positive Non-Hodgkin Lymphoma 9 September — collaboration with Oxford BioTherapeutics 25 October — initiation of phase II clinical trial of ADCETRIS in CD30-positive non-Lymphoma malignancies

2012

4 June — interim Phase I data from ASG-5ME in Prostate Cancer 5 July — initiation of global phase III trial of ADCETRIS against CD30-expressing cutaneous T-cell lymphoma 24 August — initiation of phase Ib trial of SGN-75 (INN: vorsetuzumab mafodotin) for use in combination with Everolimus in patients with renal cell carcinoma 9 October — milestone achievement under collaboration with Genentech by advancements of two anti-body conjugates into phase II trials 17 October — initiation of phase II trial of ADCETRIS in age 60+ Hodgkin Lymphoma patients 23 October — expansion of collaboration with Abbott (upront payment of $25 million, milestone payment up to $220 million) 1 November — initiation of global phase III trial of ADCETRIS in untreated advanced hodgkin lymphoma patients 26 November — received Orphan drug designation for ADCETRIS treatment of mycosis fungoides

2013

1 February — Health Canada approves ADCETRIS for treatment of relapsed refractory Hodgkin lymphoma 6 February — initiation of two phase I trials of SGN-CD19A 25 June — new collaboration with Bayer 15 July — initiation of phase I trial of SGN-CD33A in treatment of Acute Myeloid Leukemia (AML) 15 August — initiation of phase II trial of ADCETRIS for diffuse Large B-cell Lymphoma 21 October — initiation of phase I trial of SGN-LIV1A for patients with LIV-1-positive metatstatic Breast cancer

2014

29 September — Brentuximab vedotin was successfully used as a consolidation therapy in a late-stage trial for patients with a type of lymphatic cancer 8 December — Data of Brentuximab Vedotin in Diffuse Large B-cell Lymphoma presented at the Annual Meeting of the American Society of Hematology

2015

12 January  — clinical collaboration with Bristol-Myers Squibb to evaluate combination of brentuximab vedotin and nivolumab in hematologic malignancies 18 February  — Supplemental Biologics License Application (BLA) for Brentuximab Vedotin in Post-Transplant Hodgkin Lymphoma Patients at High Risk of Relapse 8 June – collaboration with Unum Therapeutics to develop and commercialise its new antibody-coupled T-cell receptor (ACTR) therapies for cancer, generating up to $645 million for Unum. 31 December — Adcetris sales increase to $226 million

2016

28 March  — the company announces it will develop 12 more drugs, employing another 100 staff

Product portfolio & pipeline

ADCETRIS used in the treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma. SGN-75 – (INN: vorsetuzumab mafodotin; a humanized IgG1 monoclonal antibody conjugated via a non-cleavable maleimidocaproyl (mc) linker with monomethyl auristatin F (MMAF), used in Phase I trial of relapsed or refractory renal cell carcinoma patients or non-Hodgkin lymphoma patients. ASG-5ME – product candidate for the treatment of solid tumours (targets SLC44A4 in pancreatic, prostate and gastric cancer). ASG-22ME – product candidate for the treatment of solid tumours (targets Nectin-4 in bladder, breast, lung and pancreatic cancer). SGN-CD19A – product candidate for the treatment of hematologic malignancies