Seattle Genetics to Present Clinical Data from Broad ADCETRIS® (Brentuximab Vedotin) Development Program and Novel Antibody-Drug Conjugates at ASH 2014

Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that multiple abstracts will be presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, California, December 6-9, 2014, highlighting the following:

• An oral presentation of phase 3 AETHERA clinical trial results for ADCETRIS (brentuximab vedotin) as consolidation therapy immediately following an autologous stem cell transplant (ASCT) in Hodgkin lymphoma (HL) patients at risk of relapse;
• Multiple presentations of ADCETRIS data in CD30-positive lymphomas, including frontline, salvage and relapsed HL, as well as diffuse large B-cell lymphoma (DLBCL) and cutaneous T-cell lymphoma (CTCL);
• First interim clinical data for SGN-CD33A in acute myeloid leukemia (AML) to be presented in an oral session;
• Updated phase 1 clinical data to be presented for SGN-CD19A in acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL); and
• Additional results from the phase 2 ROMULUS study assessing two ADC candidates that utilize Seattle Genetics’ proprietary technology being developed by Genentech, a member of the Roche Group (SIC: RO, ROG; OTCQX: RHHBY), polatuzumab vedotin and pinatuzumab vedotin (ADCs targeting CD79b and CD22, respectively).

“Antibody-drug conjugates represent an innovative and important therapeutic approach to targeting cancer. ADCETRIS, our first ADC approved by the FDA and regulatory agencies around the world, is being broadly evaluated as the foundation of care for CD30-positive malignancies. The breadth of clinical investigation is evidenced by fifteen data presentations, including the positive phase 3 AETHERA clinical trial results to be highlighted in an oral session,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “In addition to ADCETRIS, we are presenting the first clinical data for SGN-CD33A in AML, updated interim data from SGN-CD19A, and Genentech is presenting data from their phase 2 ROMULUS trial evaluating two ADCs utilizing our technology. We are looking forward to sharing these data at ASH and are pleased that ADCs continue to demonstrate encouraging clinical activity across multiple tumor types.”

With more than 15 years of experience and knowledge in ADC innovation, Seattle Genetics is the leader in developing ADCs, a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. Of the approximately 40 ADC candidates in clinical development, 25 utilize Seattle Genetics’ proprietary ADC technology. ADCETRIS is the first drug approved utilizing this technology.

Multiple corporate, investigator and collaborator presentations will be featured at ASH. Abstracts can be found at www.hematology.org and include the following:

Saturday, December 6, 2014

• Interim Analysis of a Phase 1 Study of the Antibody-Drug Conjugate SGN-CD19A in Relapsed or Refractory B-Lineage Acute Leukemia and Highly Aggressive Lymphoma (Abstract #963, poster presentation)
• Interim Analysis of a Phase 1 Study of the Antibody-Drug Conjugate SGN-CD19A in Relapsed or Refractory B-Lineage Non-Hodgkin Lymphoma (Abstract #1741, poster presentation)
• Brentuximab Vedotin in Combination with RCHOP As Front-Line Therapy in Patients with DLBCL: Interim Results from a Phase 2 Study (Abstract #1745, poster presentation)

Sunday, December 7, 2014

• Cost-Effectiveness Assessment of Brentuximab Vedotin to Prevent Progression Following Autologous Stem Cell Transplant in Hodgkin Lymphoma in the United States (Abstract #2657, poster presentation)
• Four-Year Survival Data from an Ongoing Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma (Abstract #3095, poster presentation)
• Brentuximab Vedotin (BV) Plus Rituximab (R) as Frontline Therapy for Patients (Pts) with Epstein Barr Virus (EBV)+ and/or CD30+ Lymphoma: Phase I Results of an Ongoing Phase I-II Study (Abstract #3096, poster presentation)
• Safety and Early Efficacy in an Ongoing Pilot Study of Brentuximab Vedotin and AVD Chemotherapy Followed By 30 Gray Involved-Site Radiotherapy for Newly Diagnosed, Early Stage, Unfavorable Risk Hodgkin Lymphoma (Abstract #3085, poster presentation)
• A Phase 1-2 Study of Brentuximab Vedotin (BV) and Bendamustine (B) in Patients with Relapsed or Refractory Hodgkin Lymphoma (HL) and Anaplastic Large T-Cell Lymphoma (ALCL) (Abstract #3084, poster presentation)
• Brentuximab Vedotin Followed By ABVD in Patients with Previously Untreated Hodgkin Lymphoma. A Pilot Phase II Study (Abstract #3088, poster presentation)

Monday, December 8, 2014

• Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term Outcomes (Abstract #292, oral presentation at 7:45 a.m. PT)
• Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory to Frontline Therapy (Abstract #293, oral presentation at 8:00 a.m. PT)
• Brentuximab Vedotin Monotherapy and in Combination with Dacarbazine in Frontline Treatment of Hodgkin Lymphoma in Patients Aged 60 Years and Above: Interim Results of a Phase 2 Study (Abstract #294, oral presentation at 8:15 a.m. PT)
• Results of a Phase II Trial of Brentuximab Vedotin As First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT (Abstract #501, oral presentation at 3:15 p.m. PT)
• The AETHERA Trial: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at Risk of Progression Following Autologous Stem Cell Transplant for Hodgkin Lymphoma (Abstract #673, oral presentation at 4:30 p.m. PT)
• Interim Analysis of a Phase 1 Trial of SGN-CD33A in Patients with CD33-positive Acute Myeloid Leukemia (AML) (Abstract #623, oral presentation at 5:30 p.m. PT)
• 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)
• SGN-CD33A in Combination with Cytarabine or Hypomethylating Agents Demonstrates Enhanced Anti-Leukemic Activity in Preclinical Models of AML (Abstract #3739, poster presentation)
• A Phase 2 Trial of Induction Chemotherapy with ABVD Followed by Brentuximab Vedotin Consolidation in Patients with Previously Untreated Non-Bulky Stage I or II Hodgkin Lymphoma (Abstract #4431, poster presentation)
• Updated Results of a Phase II Randomized Study (ROMULUS) of Polatuzumab Vedotin or Pinatuzumab Vedotin Plus Rituximab in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma (Abstract #4457, poster presentation)

Tuesday, December 9, 2014

• Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides or Sézary Syndrome: Final Results Show Significant Clinical Activity and Suggest Correlation with CD30 Expression (Abstract #804, oral presentation at 8:45 a.m. PT)

About ADCETRIS

ADCETRIS (brentuximab vedotin) is an ADC directed to CD30, which is known to be expressed in HL and many types of NHL, including DLBCL and CTCL. Across corporate and investigator-sponsored trials, ADCETRIS is being evaluated in more than 30 ongoing clinical trials, including four phase 3 studies. ADCETRIS is currently not approved for use as consolidation therapy immediately following an ASCT in HL patients, frontline HL, salvage HL for patients eligible for transplant, DLBCL or CTCL.

ADCETRIS is comprised of 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 but to 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 more than 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 SGN-CD33A

SGN-CD33A is a novel ADC targeted to CD33 utilizing Seattle Genetics’ newest ADC technology. CD33 is expressed on most AML cells. The CD33 antibody is attached to a highly potent DNA binding agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology (EC-mAb) allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody. The ADC is designed to be stable in the bloodstream and to release its potent DNA binding agent upon internalization into CD33-expressing cells. SGN-CD33A is being evaluated in an ongoing phase 1 clinical trial for patients with AML.

About SGN-CD19A

SGN-CD19A is an ADC targeting CD19, a protein expressed broadly on B-cell malignancies. SGN-CD19A is comprised of an anti-CD19 monoclonal antibody linked to a synthetic cytotoxic cell-killing agent, monomethyl auristatin F (MMAF). The ADC is designed to be stable in the bloodstream, and to release its cytotoxic agent upon internalization into CD19-expressing tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing the antitumor activity. SGN-CD19A is being evaluated in two ongoing phase 1 clinical trials for patients with B-cell ALL and aggressive NHL.

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 our goal to establish ADCETRIS as the foundation of therapy for a broad array of CD30-positive malignancies. 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 our other drug candidates or those of our collaborators advance in clinical trials, adverse events may occur which affect 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 June 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.