[December 08, 2014]

Seattle Genetics Presents Data from Novel Antibody-Drug Conjugate SGN-CD33A at ASH Annual Meeting

Seattle Genetics, Inc. (Nasdaq:SGEN) today presented data from an ongoing phase 1 clinical trial evaluating SGN (News - Alert)-CD33A, an antibody-drug conjugate (ADC) in development for the treatment of acute myeloid leukemia (AML), at the 56^th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, CA (News - Alert) December 6-9, 2014. SGN-CD33A is a novel ADC targeted to CD33 utilizing Seattle Genetics' newest technology. CD33 is expressed on most AML cells regardless of subtype, cytogenetic abnormality or underlying mutational heterogeneity. SGN-CD33A is the first ADC (News - Alert) utilizing an engineered cysteine antibody (EC-mAb) and pyrrolobenzodiazepine (PBD) dimer to be advanced into the clinic.

"There is a significant need for improved treatment options for acute myeloid leukemia where patient outcomes and overall survival have not meaningfully changed in the past three decades, particularly for patients unable to undergo intensive chemotherapy," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "The data presented at ASH on SGN-CD33A demonstrate encouraging anti-leukemic activity with a manageable safety profile in primarily elderly, relapsed patients who were not candidates for other therapies. We are pleased to see a high percentage of patients with marked and rapid reduction in bone marrow blasts and low rates of off-target toxicity and 30-day mortality, in addition to observing complete remissions or complete remissions with incomplete recovery across multiple dose levels. We continue to evaluate SGN-CD33A in this trial, and plan to broaden the clinical program to include a phase 1b trial in combination with standard frontline induction and consolidation agents for AML in the near future."

"From my experience in treating acute myeloid leukemia, it is notable to see a single agent treatment resulting in bone marrows with no detectable blasts, even by highly sensitive flow cytometry," said Eytan Stein, M.D., Memorial Sloan Kettering Cancer Center. "The SGN-CD33A data presented today are encouraging and show single agent anti-leukemic activity evidenced by a bone marrow blast clearance in 44 percent of patients. This appears to be a highly active agent with a manageable safety profile, and I look forward to evaluating it further as a potential treatment for acute myeloid leukemia."

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 on Monday, December 8, 2014 at the Moscone Center South Building, Gateway (News - Alert) Ballroom 103)

Data were reported from 56 evaluable AML patients with a median age of 75 years and predominantly intermediate or adverse cytogenetic risk. Of the 56 patients, 43 percent had received intensive therapy and 57 percent had declined intensive therapy. More than 50 percent of patients had evidence of underlying myelodysplasia.

The primary endpoints of the trial are the estimation of the maximum tolerated dose and evaluation of the safety of SGN-CD33A. In addition, the trial is evaluating anti-leukemic activity, pharmacokinetics, progression-free survival and overall survival in patients with CD33-positive AML.

Key findings presented by Dr. Stein include:

• Of the 52 evaluable patients treated across all dose levels, the best clinical response by investigator included 11 patients (21 percent) with a complete remission or complete remission with incomplete recovery (CR/CRi). An additional 12 patients (23 percent) achieved a morphologic leukemia free state.
• Data suggest an emerging dose-response relationship with rapid and marked decreases in bone marrow blasts. Of the 17 response-evaluable patients treated at 40 micrograms per kilogram (mcg/kg), five patients (29 percent) achieved a CR/CRi. At last follow-up, 12 of 18 patients (67 percent) treated at this dose level remained alive. Ten patients treated at this dose level were elderly and had declined intensive therapy, of which four patients (40 percent) achieved CR/CRi.
• Among patients treated at the 40 mcg/kg dose level or higher, 77 percent (17 of 22) had a 50 percent or more reduction in bone marrow blasts.
• For CR/CRi patients, median time to neutrophil count recovery was 6.7 weeks and median time to platelet count recovery was 12 weeks.
• The most common treatment-related adverse events of any grade occurring in 15 percent or more of patients were febrile neutropenia (32 percent), fatigue (20 percent) and low blood platelet count (16 percent); the most common post-baseline Grade 3 or 4 laboratory abnormalities were low blood neutrophil count (98 percent), low blood leukocyte count (97 percent) and low blood platelet count (87 percent).
• The 30-day mortality rate was two percent, with no treatment-related deaths occurring during that time.
• The maximum tolerated dose (MTD) has not been reached and dose exploration is continuing, including combination cohorts with hypomethylating agents.

SGN-CD33A in Combination with Cytarabine or Hypomethylating Agents Demonstrate Enhanced Anti-leukemic Activity in Preclinical Models of AML (Abstract #3739, poster presentation at 6:00 p.m. PT on Monday, December 8, 2014 at the Moscone Center North Building, Hall E)

A preclinical analysis evaluated the activity of SGN-CD33A in combination with therapies commonly used to treat AML, including cytarabine and hypomethylating agents, in multi-drug resistant AML models. Data presented in a poster presentation by May Sutherland, Ph.D., Seattle Genetics, demonstrated enhanced anti-leukemic activity observed with the combination of SGN-CD33A and cytarabine or hypomethylating agents as well as synergistic mechanisms of action and anti-tumor activity. In addition, use of hypomethylating agents increased CD33 levels on AML cells.

About SGN-CD33A

SGN-CD33A is comprised of three parts: A cysteine-engineered anti-CD33 antibody enabling uniform site-specific conjugation, a cleavable dipeptide linker that is highly stable in circulation, and a PBD dimer that binds DNA with high intrinsic affinity. PBD dimers are a class of DNA-crosslinking agents significantly more potent than systemic chemotherapeutic drugs. Seattle Genetics has been working with PBDs since 2009 under an exclusive research and licensing arrangement with Spirogen Ltd. Over the past four years, Seattle Genetics has selected and optimized specific PBD molecules for its proprietary use in ADCs. In addition, SGN-CD33A employs a novel linker system and proprietary, site-specific conjugation technology (EC-mAb) that 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 cytotoxic agent upon internalization into CD33-expressing cells.

About Acute Myeloid Leukemia

Acute myeloid leukemia, also called acute myelocytic leukemia or AML, is an aggressive type of cancer of the bone marrow and blood that progresses rapidly without treatment. AML is a cancer that starts in the cells that are supposed to mature into different types of blood cells. AML starts in the bone marrow (the soft inner part of the bones, where new blood cells are made) and quickly moves into the blood. According to the American Cancer Society, in 2014 more than 18,500 new cases of AML (mostly in adults) will be diagnosed and nearly 10,500 deaths will occur from AML (almost all will be in adults).

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.

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of SGN-CD33A. 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 the inability to show sufficient activity in the clinical trials and risk of adverse events as SGN-CD33A advances in clinical trials. 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.

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