Seattle Genetics Presents ADCETRIS® (Brentuximab Vedotin) Data in Diffuse Large B-cell Lymphoma at ASH Annual Meeting

Seattle Genetics, Inc. (Nasdaq: SGEN) today highlighted two separate ADCETRIS (brentuximab vedotin) data presentations in relapsed/refractory and frontline diffuse large B-cell lymphoma (DLBCL) at the 56^th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, CA, December 6-9, 2014. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical Hodgkin lymphoma, anaplastic large cell lymphoma and several other types of non-Hodgkin lymphoma.

“DLBCL is an aggressive type of non-Hodgkin lymphoma that is typically considered incurable in the relapsed/refractory post-transplant setting with a median survival of approximately four months,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “The updated phase 2 data at ASH demonstrate encouraging activity of ADCETRIS in relapsed/refractory DLBCL, even when CD30 is undetectable by standard immunohistochemistry methods. In addition, our data show that ADCETRIS can be safely combined with RCHOP in the frontline setting with a strong complete remission rate in high-intermediate and high-risk patients. The activity observed supports our plans to initiate a randomized phase 2 clinical trial of ADCETRIS for relapsed CD30-positive DLBCL patients during 2015 and to pursue possible frontline DLBCL combination trials.”

Brentuximab Vedotin Monotherapy in DLBCL Patients with Undetectable CD30: Preliminary Results from a Phase 2 Study (Abstract #629, oral presentation at 5:30 p.m. PT at the Moscone Center, South Building, Esplanade 304-306-308)

An ongoing phase 2 clinical trial in relapsed or refractory DLBCL includes three treatment arms to evaluate ADCETRIS in CD30-positive disease, CD30-undetectable disease and in combination with Rituxan (rituximab). Data were reported from 51 patients with CD30-undetectable DLBCL using standard immunohistochemistry (IHC) testing. The median age of patients was 65 years, 71 percent were refractory to frontline therapy and 61 percent were refractory to their most recent prior therapy. Patients were treated with single-agent ADCETRIS every three weeks. The trial was designed to assess the antitumor activity and safety profile and evaluate CD30 expression. Key findings presented by Tanya Siddiqi, M.D., City of Hope National Medical Center, include:

• Of 42 evaluable patients in the CD30-undetectable DLBCL arm treated with single-agent ADCETRIS, 13 patients (31 percent) had an objective response, including four patients (10 percent) with a complete remission and nine patients (21 percent) with a partial remission.
• Median progression-free survival was 1.4 months (range, 0.4 to 9+).
• Median duration of response had not yet been reached for patients with a complete remission and was 1.6 months for patients with a partial remission.
• Among 35 patients with baseline and post-baseline assessments, 63 percent achieved tumor reduction.
• The most common adverse events of any grade occurring in greater than 15 percent of patients were nausea (29 percent); fatigue and peripheral sensory neuropathy (22 percent each); anemia and constipation (20 percent each); diarrhea and neutropenia (18 percent each); and abdominal pain and pyrexia (16 percent each).
• The most common Grade 3 or 4 adverse events occurring in more than one patient were neutropenia (seven patients), anemia (three patients) and diarrhea and febrile neutropenia (two patients each).
• Updated efficacy data were also reported from 48 DLBCL patients in the CD30-positive arm treated with single-agent ADCETRIS demonstrating a 44 percent objective response rate, including 17 percent complete remissions, and a median progression-free survival of 4.0 months (range, 0.6+ to 24+).

Based on the activity demonstrated by ADCETRIS in relapsed/refractory DLBCL, the company plans to initiate a randomized phase 2 trial during 2015 for patients with CD30-positive DLBCL who have relapsed following autologous stem cell transplant or who are ineligible for transplant. This trial will randomize patients to receive Rituxan and bendamustine with or without ADCETRIS.

Brentuximab Vedotin in Combination with RCHOP as Front-line Therapy in Patients with DLBCL: Interim Results from a Phase 2 Study (Abstract #1745, poster presented on Saturday, December 6, 2014)

Data were reported from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with the standard of care regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (A+RCHOP) in frontline high-intermediate and high-risk DLBCL patients. Patients were randomized to receive standard dose RCHOP with either 1.2 milligrams per kilogram (mg/kg) or 1.8 mg/kg of ADCETRIS every three weeks.

Data were reported from 47 patients with a median age of 67 years. Nearly all patients (95 percent) had stage III/IV disease at the time of diagnosis and were considered either high-risk (38 percent) or high-intermediate risk (62 percent). As a part of the trial design, a Safety Monitoring Committee reviewed safety data after ten patients in each arm had completed treatment, and recommended continuing with a dose of 1.2 mg/kg of ADCETRIS. Interim data from this phase 2 trial were highlighted in a poster presentation by Christopher Yasenchak, M.D., Willamette Valley Cancer Institute and Research Center/US Oncology Research, include:

• Of 22 patients in both arms evaluable for response, 21 patients (95 percent) had an objective response, including 17 patients (77 percent) with a complete remission and four patients (18 percent) with a partial remission. One patient had progressive disease.
• Antitumor activity was not significantly different between the two dosage arms. In the arm with the recommended dose of 1.2 mg/kg of ADCETRIS plus RCHOP, all 13 evaluable patients had an objective response, including eight patients (80 percent) with a complete remission and two patients (20 percent) with a partial remission.
• Preliminary data suggest a higher complete remission rate in CD30-positive patients (greater than 90 percent) versus CD30-undetectable DLBCL patients.
• Across both treatment arms, 100 percent of patients achieved tumor reduction.
• ADCETRIS administered at 1.2 mg/kg in combination with RCHOP had a similar safety profile to that expected from RCHOP alone in this patient population.
• The most common adverse events occurring in more than 25 percent of patients of any grade in the RCHOP plus 1.2 mg/kg of ADCETRIS arm were nausea (38 percent), fatigue and diarrhea (33 percent each), anemia (30 percent), peripheral sensory neuropathy and febrile neutropenia (29 percent each).
• The most common Grade 3 or 4 adverse events in the RCHOP plus 1.2 mg/kg of ADCETRIS arm were neutropenia, febrile neutropenia, anemia, weight loss and insomnia.

The company plans to add a cohort of CD30-positive DLBCL patients to this trial evaluating ADCETRIS plus RCHP (removing vincristine from the regimen) to support future development of ADCETRIS in frontline DLBCL.

ADCETRIS is currently not approved for the treatment of DLBCL.

About Diffuse Large B-Cell Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma represents a diverse group of cancers that develop in the lymphatic system and are characterized by uncontrolled growth and accumulation of abnormal lymphocytes. Lymphocytes are a type of blood cells that are responsible for defending the body against infection. The most common forms of non-Hodgkin lymphoma are diffuse large B-cell lymphoma (an aggressive subtype) and follicular lymphoma (an indolent subtype).

About ADCETRIS

ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream and release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection received accelerated approval from the U.S. Food and Drug Administration and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of ASCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in 45 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda will be solely responsible for development costs.

About Seattle Genetics

Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS^® (brentuximab vedotin) is an ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available for two indications in more than 45 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME and ASG-15ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.

ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

BOXED WARNING

Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.

Contraindication:

Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.

Warnings and Precautions:

• Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
• Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy.
• Hematologic toxicities: Grade 3 or 4 anemia, thrombocytopenia and prolonged (≥1 week) severe neutropenia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Closely monitor patients for fever. If Grade 3 or 4 neutropenia develops, manage by G-CSF support, dose delays, reductions or discontinuation.
• Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia and sepsis/septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.
• Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
• Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
• Stevens-Johnson syndrome (SJS): SJS has been reported with ADCETRIS. If SJS occurs, discontinue ADCETRIS and administer appropriate medical therapy.
• Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women of the potential hazard to the fetus.

Adverse Reactions:

ADCETRIS was studied as monotherapy in 160 patients in two Phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.

Drug Interactions:

Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to MMAE.

Use in Specific Populations:

MMAE exposure is increased in patients with hepatic impairment and severe renal impairment. Closely monitor these patients for adverse reactions.

For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com.

Certain of the statements made in this press release are forward looking, such as those, among others, relating to ADCETRIS as a therapy for diffuse large B-cell lymphoma. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include risks that data resulting from additional trials with ADCETRIS will not support approvals in any of the studied indications. In addition, as other drug candidates or those of our collaborators advance in clinical trials, adverse events may occur which effect the future development of those drug candidates and possibly other compounds using similar technology. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-Q for the quarter ended September 30, 2014 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.