Seattle Genetics Highlights Vadastuximab Talirine (SGN-CD33A) Data Presentations In Patients With Acute Myeloid Leukemia At American Society of Hematology 2015

ORLANDO, Fla.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq: SGEN) today highlighted several data presentations at the 57^th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in Orlando, Florida, December 5-8, 2015, evaluating vadastuximab talirine (SGN-CD33A; 33A) in combination with hypomethylating agents (HMAs; azacitidine, decitabine) in frontline acute myeloid leukemia (AML) and as monotherapy in primarily relapsed AML. 33A is an antibody-drug conjugate (ADC) targeted to CD33 utilizing Seattle Genetics’ newest technology, comprising an engineered cysteine antibody (EC-mAb) stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer. CD33 is expressed on leukemic blasts in nearly all AML patients and expression is generally not influenced by subtype, cytogenetic abnormality or underlying mutations.

“There is a dire need to improve outcomes for older patients with AML”

Based on interim data from the ongoing phase 1 clinical trial, a phase 3 clinical trial is planned to begin in 2016. The phase 3 study will evaluate 33A in combination with HMAs in previously untreated older AML patients. Seattle Genetics is also evaluating 33A broadly across multiple lines of therapy in patients with myeloid malignancies, including in ongoing and planned phase 1 and 2 clinical trials for newly diagnosed or relapsed AML and for newly diagnosed myelodysplastic syndrome (MDS). 33A was recently granted Orphan Drug Designation by both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of AML. FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States. More information about 33A and ongoing clinical trials can be found at www.ADC-CD33.com.

“For decades, little progress has been made in improving treatment outcomes for AML patients. Older AML patients have particularly poor outcomes and most do not tolerate intensive therapies,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Hypomethylating agents are a standard of care for these patients, but deliver low response rates and median overall survival of 10 months or less. We are committed to improving the therapeutic options for AML patients through innovative, targeted approaches. Based on the phase 1 data at ASH, we plan to advance 33A into a randomized phase 3 clinical trial in combination with HMAs for newly diagnosed older AML patients in 2016.”

“There is a dire need to improve outcomes for older patients with AML,” said Amir Fathi, M.D., Massachusetts General Hospital Cancer Center. “I am pleased with the anti-leukemic activity we have observed in phase 1 clinical trials evaluating 33A both as monotherapy and combination therapy in AML patients. This is an incredibly difficult disease to treat and the results to-date, especially in combination therapy, show a balance of activity and tolerability together with low early mortality rates. The response rates and durable remissions with 33A treatment compare favorably to the current standard of care.”

SGN-CD33A Plus Hypomethylating Agents: A Novel, Well-Tolerated Regimen with High Remission Rate in Frontline Unfit AML (Abstract #454, oral presentation on Monday, December 7, 2015 at 7:45 a.m. ET)

Outcomes for AML patients who are not candidates for intensive chemotherapy or allogeneic stem cell transplant are dismal. Low intensity treatment options, including HMAs (azacitidine and decitabine), are limited with complete remission and complete remission with incomplete platelet or neutrophil recovery (CR/CRi) rates of 17.8 to 27.8 percent and median overall survival of 7.7 to 10.4 months. Interim results from an ongoing phase 1 study evaluating 33A in combination with HMAs were presented for the first time.

Data were reported from 25 frontline unfit AML patients with a median age of 77 years and predominantly intermediate or adverse cytogenetic risk who had declined intensive therapy. Forty-eight percent of patients had evidence of underlying myelodysplasia. Key findings presented by Dr. Fathi include:

• Of 23 efficacy-evaluable patients treated with azacitidine or decitabine combination therapy with 33A, the best clinical response by investigator included 15 patients (65 percent) with a CR or CRi. Responses were observed in higher-risk patients, with remission achieved in eight of 10 patients (80 percent) with underlying myelodysplasia and eight of nine patients (89 percent) with adverse cytogenetics.
• At a median follow-up of 7.7 months, median survival had not yet been reached and 72 percent of patients remained alive and on study. The 30- and 60-day mortality rates were zero and four percent, with no treatment-related deaths occurring during that time.
• Ninety-six percent of patients (22 of 23) had reduction in bone marrow blasts, with 87 percent (20 of 23) experiencing a reduction of 50 percent or greater.
• The most common treatment-related adverse events of any grade occurring in 20 percent or more of patients were fatigue (40 percent), nausea (32 percent), febrile neutropenia (28 percent), thrombocytopenia (24 percent) and neutropenia and anemia (20 percent each). The most common Grade 3 or 4 treatment-emergent adverse events occurring in 20 percent or more of patients were febrile neutropenia (56 percent), thrombocytopenia (32 percent), neutropenia (28 percent), anemia (24 percent) and fatigue (20 percent).

A Phase 1 Trial of SGN-CD33A As Monotherapy in Patients with CD33-Positive Acute Myeloid Leukemia (Abstract #324, oral presentation on Sunday, December 6, 2015 at 5:45 p.m. ET)

Data were reported from 93 AML patients treated with 33A monotherapy with a median age of 74 years and predominantly intermediate or adverse cytogenetic risk. The disease status of the 93 patients was a mixed AML population, consisting of mostly relapsed patients, but also a small percentage of older newly diagnosed patients. Of the 93 patients, 37 percent had previously received intensive therapy, 44 percent had received prior non-intensive therapy and 19 percent had declined intensive therapy. More than 58 percent of patients had evidence of underlying myelodysplasia.

Key findings presented by Anthony Stein, M.D., City of Hope, include:

• Of the 85 evaluable patients treated across all dose levels, 48 percent experienced blast clearance, including 23 patients (27 percent) with a CR or CRi. Of the 27 response-evaluable patients treated at the recommended monotherapy dose of 40 micrograms per kilogram (mcg/kg), 11 patients (41 percent) achieved a CR/CRi. Of 12 treatment naïve patients who were treated at 40 mcg/kg, seven patients (58 percent) achieved CR/CRi.
• Among all patients treated at the 40 mcg/kg dose level or higher, 91 percent had a reduction in bone marrow blasts, with a majority experiencing a reduction of 50 percent or greater. The median overall survival for these predominantly relapsed AML patients was 8.9 months (95% C.I. 3.9, 13.7).
• For patients achieving CR/CRi, 73 percent were negative for minimal residual disease.
• The 30- and 60-day mortality rates were five and 27 percent.
• The most common treatment-related adverse events of any grade occurring in 15 percent or more of patients were febrile neutropenia (39 percent), fatigue (27 percent), thrombocytopenia (26 percent), anemia (24 percent) and neutropenia (16 percent); the most common Grade 3 or higher adverse events occurring in 20 percent or more of patients were febrile neutropenia (66 percent), thrombocytopenia (28 percent) and anemia (24 percent).

SGN-CD33A in Combination with Hypomethylating Agents is Highly Efficacious in Preclinical Models of AML (Abstract #3785, poster presentation on Monday, December 7, 2015)

A preclinical analysis evaluated the activity of 33A in combination with HMAs, azacitidine and decitabine, in AML models. Data presented in a poster presentation demonstrated enhanced cytotoxicity observed with the combination of 33A and HMAs as well as synergistic mechanisms of action and antitumor activity. In particular, HMA priming appears to increase CD33 expression and enhance DNA incorporation of PBDs released from 33A.

SGN-CD123A, a Pyrrolobenzodiazepine Dimer Linked Anti-CD123 Antibody Drug Conjugate, Demonstrates Effective Anti-Leukemic Activity in Multiple Preclinical Models of AML (Abstract #330, oral presentation on Sunday, December 6, 2015 at 5:45 p.m. ET)

Preclinical data from a novel ADC called SGN-CD123A, consisting of an anti-CD123 antibody attached to a PBD dimer, were also featured in an oral presentation at ASH. CD123 is expressed across AML subtypes, and is particularly prominent on leukemic stem cells, which are difficult to kill and may be responsible for high relapse rates even following intensive therapy. Data presented in an oral session by Eric Feldman, M.D., Senior Medical Director at Seattle Genetics, demonstrated enhanced anti-leukemic activity observed across multiple AML cell lines, including four out of five multi-drug resistant cell lines, and in 20 of 23 AML patient samples. In addition, antitumor activity was observed in all of the in vivo models tested. These preclinical data support a phase 1 clinical trial of SGN-CD123A in AML planned to begin in the second-half of 2016.

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 2015 more than 20,500 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 Vadastuximab Talirine (SGN-CD33A)

Vadastuximab talirine (SGN-CD33A; 33A) 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. 33A is being evaluated in ongoing phase 1 and phase 1/2 clinical trials and a planned pivotal phase 3 clinical trial for patients with AML.

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 a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available in more than 55 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 in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including vadastuximab talirine (SGN-CD33A; 33A), denintuzumab mafodotin (SGN-CD19A; 19A), SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. 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 our intention to initiate a phase 3 clinical trial in 2016 to evaluate 33A in combination with HMAs in previously untreated older AML patients and the therapeutic potential of vadastuximab talirine (SGN-CD33A; 33A) or SGN-CD123A. 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 vadastuximab talirine and SGN-CD123A advance in clinical trials even after promising results in earlier clinical trials. In addition, as our drug candidates or those of our collaborators advance in clinical trials, adverse events and/or regulatory actions 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 under the caption “Risk Factors” included in the company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 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.