Year: 2016

8-K – Current report

On February 22, 2016 PDL BioPharma, Inc. (PDL) (NASDAQ: PDLI) reported financial results for the fourth quarter and twelve months ended December 31, 2015 (Filing, 8-K, PDL BioPharma, FEB 22, 2016, View Source [SID:1234509130]).

Total revenues in 2015 increased two percent to $590.4 million from $581.2 million in 2014. Revenues for the year ended December 31, 2015 included $485.2 million in royalties from PDL’s licensees to the Queen et al. patents, $68.4 million in net royalty payments from acquired royalty rights and a change in fair value of the royalty rights assets, which included approximately $43.4 million in net cash royalty payments, $36.2 million in interest revenue from notes receivable debt financings to late-stage healthcare companies, and $0.7 million in realized gains from the sale of PDL’s investment in AxoGen Inc. common stock. During the years ended December 31, 2015 and 2014, our Queen et al. royalty revenues consisted of royalties and maintenance fees earned on sales of products under license agreements associated with our Queen et al. patents. During the years ended December 31, 2015 and 2014, royalty rights – change in fair value consisted of revenues associated with the change in estimated fair value of our royalty right assets, primarily Depomed, Inc., The Regents of the University of Michigan, Viscogliosi Brothers, LLC, ARIAD Pharmaceuticals Inc. and AcelRx Pharmaceuticals, Inc. The full year 2015 revenue growth over the full year 2014 is driven by increased sales of Perjeta, Xolair, and Kadcyla by PDL’s licensees, an increase in the estimated fair value of the acquired royalty rights from the Company’s purchase of Depomed’s diabetes-related royalties, as well as a foreign exchange gain and lower rebate paid to Novartis AG for Lucentis, partially offset by decreased interest revenues due to the early payoff of the AxoGen and Durata Therapeutics, Inc. notes receivables.

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Total revenues for the fourth quarter of 2015 increased 52 percent, to $178.1 million from $117.1 million in the fourth quarter of 2014. Revenues for the fourth quarter of 2015 included $121.2 million in royalty payments from PDL’s licensees to the Queen et al. patents, $49.1 million in net royalty payments from acquired royalty rights and a change in fair value of the royalty rights assets, which included approximately $34.4 million in net cash royalty payments, $7.6 million in interest revenue from notes receivable debt financings to late-stage healthcare companies, and $0.1 million in realized gains from the sale of PDL’s investment in AxoGen common stock. The fourth quarter of 2015 revenue growth over the fourth quarter of 2014 is driven by the change in estimated fair value of our royalty right assets, primarily Depomed, Inc.

Operating expenses in 2015 were $40.1 million, compared with $34.9 million in 2014. Operating expenses in the fourth quarter of 2014 were $16.5 million, compared with $17.7 million in 2014. The increase in operating expenses for the year ended December 31, 2015, when compared to the year ended December 31, 2014, was a result of total restructuring costs of $7.9 million in connection with the LENSAR notes receivable extinguishment, which is comprised of a loss on extinguishment of notes receivable of $4.0 million primarily related to a lower estimated fair value of the ALPHAEON Class A common stock, and additional general and administrative expenses of $3.9 million for closing and legal fees related to the LENSAR notes receivable restructuring, and other legal expenses mostly related to $1.2 million in funding the ongoing operation management of Wellstat Diagnostics, partially offset by a decrease in professional services from asset acquisition expenses. The decrease in operating expenses for the quarter ended December 31, 2015, when compared to the quarter ended December 31, 2014, was a result of a decrease in professional services from asset acquisition expenses and a decrease in compensation related expenses,

partially offset by the LENSAR restructuring loss and other closing fees, and an increase for legal expenses mostly related to Wellstat ongoing operation management.

Net income in 2015 was $332.8 million, or $2.03 per diluted share as compared with net income in 2014 of $322.2 million, or $1.86 per diluted share. Net income for the fourth quarter of 2015 was $100.6 million, or $0.61 per diluted share, as compared with net income of $55.1 million in the same period of 2014, or $0.32 per diluted share.

Net cash provided by operating activities in 2015 was $301.5 million, compared with $292.3 million in the same period in 2014. PDL had cash, cash equivalents and short-term investments of $220.4 million and $293.7 million at December 31, 2015 and 2014, respectively. The decrease was primarily attributable to the extinguishment of convertible notes of $220.4 million, purchase of royalty rights at fair value of $115.0 million, payment of dividends of $98.3 million, repayment of a portion of the March 2015 Term Loan of $75.0 million, purchase of notes receivable of $35.2 million, and payment of debt issuance costs related to the February 2018 Note issuance of $0.6 million, partially offset by proceeds from the March 2015 Term Loan of $100.0 million, proceeds from royalty rights of $43.4 million, repayment of notes receivables of $25.2 million, sale of investments of $1.9 million, and cash generated by operating activities of $301.5 million.

Recent Developments

In December 2015, Lion Buyer, a wholly owned subsidiary of ALPHAEON assumed $42.0 million in loans as part of the borrowings under PDL’s prior credit agreement with LENSAR and changed its name to LENSAR, LLC in connection with ALPHAEON’s acquisition of substantially all of the assets of LENSAR. In addition, ALPHAEON issued 1.7 million shares of its Class A common stock to PDL for an estimated fair value of $3.84 per share.

In December 2015 and January 2016, PDL and Direct Flow Medical modified the existing credit agreement. PDL funded an additional $5.0 million to Direct Flow Medical in the form of a short-term secured promissory note that we expect will be converted into a loan under the credit agreement with substantially the same interest and payment terms as the existing loans.

PDL’s $100.0 million term loan entered into on March 20, 2015 with the Royalty Bank of Canada was repaid with the final principal payment of $25.0 million plus accrued interest paid on February 12, 2016.

On February 18, 2016, PDL was advised that Sanofi and kaléo will terminate their license and development agreement later this year. At that time, all U.S. and Canadian commercial and manufacturing rights to Auvi-Q will be returned to kaléo, and they intend to evaluate the timing and options for bringing Auvi-Q back to the market. PDL entered into a secured note purchase agreement with Accel 300, a wholly-owned subsidiary of kaléo, which as of December 31, 2015, had a principal balance of $144.8 million due to PDL. An interest reserve account previously set up as part of the note agreement will substantially cover interest payments due to PDL through the end of the second quarter of 2016, and kaléo has indicated that it intends to make payments due to PDL under the note agreement until Auvi-Q is returned to the market.

2016 Dividends
On January 26, 2016, our board of directors declared a quarterly dividend to be paid to our stockholders in the first quarter of 2016 of $0.05 per share of common stock, payable on March 11, 2016 to stockholders of record on March 4, 2016, the record date of the dividend payment. At the same time our board of directors elected to announce its future dividend plans on a quarter by quarter basis, rather than for the full year as was the previous practice, to allow greater flexibility and focus on long term growth. Our board of directors evaluates the financial condition of the Company and considers the economic outlook, profitability, corporate cash flow, the Company’s liquidity needs and the health and stability of credit markets when determining the dividend.

FDA Accepts For Review Supplemental New Drug Application for XTANDI® (enzalutamide) Capsules in Metastatic Castration-resistant Prostate Cancer with Data from Head-to-Head Studies of Enzalutamide Versus Bicalutamide

On February 22, 2016 Astellas Pharma Inc. (TSE: 4503) and Medivation, Inc. (Nasdaq: MDVN) reported that the U.S. Food and Drug Administration (FDA) has accepted for review a supplemental New Drug Application (sNDA) that they have submitted for XTANDI (enzalutamide) capsules in metastatic castrationresistant prostate cancer (mCRPC), which includes findings from the Phase 2 TERRAIN and STRIVE studies, to update the relevant clinical sections within the current indication (Press release, Astellas, FEB 22, 2016, View Source [SID:1234509138]).

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Enzalutamide is approved by the FDA for the treatment of patients with mCRPC. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is October 22, 2016.

A Type-II variation to update the Summary of Product Characteristics (SmPC) has also been submitted to the European Medicines Agency.

About the TERRAIN trial
The Phase 2 TERRAIN trial enrolled 375 patients in North America and Europe. The trial enrolled patients with metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration. The primary endpoint of the trial was progression-free survival (PFS), defined as time from randomization to centrally confirmed radiographic progression, skeletal-related event, initiation of new anti-neoplastic therapy or death, whichever occurred first. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus bicalutamide at a dose of 50 mg taken once daily, the approved dose in combination with an LHRH analogue.

About the STRIVE trial
The Phase 2 STRIVE trial enrolled 396 CRPC patients in the U.S. The trial randomized 257 2 patients with metastatic prostate cancer and 139 patients with non-metastatic prostate cancer whose disease progressed despite treatment with a LHRH analogue therapy or following surgical castration. The primary endpoint of the trial was PFS, defined as time from randomization to radiographic (bone or soft tissue) progression, prostate-specific antigen (PSA) progression (defined by Prostate Cancer Working Group 2 criteria), or death due to any cause, whichever occurs first. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken once daily (n=198) versus bicalutamide at a dose of 50 mg taken once daily (n=198), the approved dose in combination with a LHRH analogue.

About XTANDI (enzalutamide) capsules
XTANDI is approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Enzalutamide Mechanism of Action
Enzalutamide is an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within the tumor cell. In preclinical studies, enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors, and inhibit androgen receptor nuclear translocation and interaction with DNA. The clinical significance of this MOA is unknown.

Important Safety Information
Contraindications XTANDI is not indicated for women and is contraindicated in women who are or may become pregnant. XTANDI can cause fetal harm when administered to a pregnant woman.

Warnings and Precautions
Seizure In Study 1, conducted in patients with metastatic castration-resistant prostate cancer (CRPC) who previously received docetaxel, seizure occurred in 0.9% of XTANDI patients and 0% of placebo patients. In Study 2, conducted in patients with chemotherapy-naive metastatic CRPC, seizure occurred in 0.1% of XTANDI patients and 0.1% of placebo patients. There is no clinical trial experience re- administering XTANDI to patients who experienced a seizure, and limited safety data are available in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold; Study 2 permitted the use of these medications. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Adverse Reactions The most common adverse reactions (≥ 10%) reported from two combined clinical studies that occurred more commonly (≥ 2% over placebo) in XTANDI patients were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. 3 In Study 1, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In Study 2, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups.

• Lab Abnormalities: Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).

• Infections: In Study 1, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.

• Falls (including fall-related injuries), occurred in 9% of XTANDI patients and 4% of placebo patients. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas.

• Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of all patients.

Drug Interactions
Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If coadministration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

For Full Prescribing Information for XTANDI (enzalutamide) capsules, please visit View Source

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‐800‐FDA‐1088.

OncoMed Presents Updated Phase 1b Data for Tarextumab in Small Cell Lung Cancer

On February 22, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported updated survival data from a Phase 1b clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) for the treatment of small cell lung cancer (Press release, OncoMed, FEB 22, 2016, View Source [SID:1234509129]).

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The Phase 1b dose-escalation trial enrolled 27 previously untreated patients with extensive-stage small cell lung cancer to assess the safety, biomarker, and anti-tumor activity of tarextumab in combination with etoposide and platinum-based chemotherapy. Doses of tarextumab ranged from 5 mg/kg to 15 mg/kg and a Phase 2 combination dose of 15mg/kg every three weeks was selected. Among all patients in the trial, median progression-free survival (PFS) was 4.4 months and the median overall survival (OS) was 10.3 months. Additional survival benefit was observed in 15 patients who received higher doses of tarextumab (at or above 12.5 mg/kg every three weeks) in combination with standard-of-care therapy, with a median PFS of 5.8 months and median OS of 16 months.

"These more mature follow-up data from our Phase 1b trial of tarextumab plus chemotherapy in small cell lung cancer patients provide early signs of encouraging efficacy. Of note, we are seeing a dose-efficacy association with a manageable side effect profile for tarextumab in the small cell lung cancer Phase 1b clinical trial. This Phase 1b data supports our ongoing Phase 2 PINNACLE trial," said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer. "Small cell lung cancer responds quickly to chemotherapy, but has a high rate of recurrence. By targeting cancer stem cells, and Notch3 in particular, we hope to have a positive impact on patient outcomes."

Additional Phase 1b Results

On-target adverse events associated with tarextumab included diarrhea, fatigue, nausea and decreased appetite. These were mostly Grade 1 or 2 events, and manageable with supportive care. No dose-limiting toxicities were observed at the Phase 2 dose of 15 mg/kg with platinum-based chemotherapy and etoposide.

As previously reported at the 2015 ASCO (Free ASCO Whitepaper) Annual Meeting, 77 percent of evaluable patients achieved RECIST responses and six achieved stable disease for an overall clinical benefit rate of 100 percent. Greater tumor size reductions were observed among those patients who received doses of tarextumab at or above 12.5 mg/kg.

The updated survival data from the Phase 1b PINNACLE study were recently presented by Anne Chiang, M.D., Ph.D., of the Yale School of Medicine, during the 16th Annual Targeted Therapies of Lung Cancer Meeting.

OncoMed is conducting the PINNACLE Phase 1b/2 clinical trial of tarextumab for the treatment of small cell lung cancer. The randomized Phase 2 trial is comparing progression-free survival (PFS) outcomes for patients treated with tarextumab administered at 15 mg/kg every three weeks in combination with etoposide and cisplatin or carboplatin versus patients who receive placebo plus chemotherapy. Additionally, PFS will be assessed using a predictive biomarker for high tumor Notch3 expression. Secondary endpoints for the Phase 2 study include overall survival, overall response rate, pharmacokinetics, safety and other biomarkers. The PINNACLE study is being conducted at about 40 sites in the U.S. and is expected to enroll approximately 130 patients. Results from the Phase 2 PINNACLE trial are anticipated in early 2017.

Patients interested in participating in the tarextumab small cell lung cancer study may learn more by calling 1-866-914-7347 or emailing [email protected].

About Small Cell Lung Cancer

According to the American Cancer Society, lung cancer (both small cell and non-small cell) is the second most common cancer in men and women and is by far the leading cause of cancer death. Small cell lung cancer is expected to make up about 10%-15% of the 221,200 newly diagnosed lung cancer cases and the 158,040 deaths estimated to occur in the U.S. in 20151. SCLC tends to grow and spread quickly, and is typically not discovered until it has metastasized to other parts of the body (extensive stage). The current standard of care in treating small cell lung cancer is the chemotherapeutic etoposide in combination with either cisplatin or carboplatin (platinum therapy). In spite of a high sensitivity to chemotherapy and remission rates of up to 80% following initial treatment, the median overall survival is six-twelve months for patients with extensive stage disease2.

About Tarextumab (anti-Notch2/3, OMP-59R5)

Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment.

Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.

FDA Grants Orphan Drug Designation to Bellicum’s BPX-501 for the Treatment of Immunodeficiency and GvHD Following Stem Cell Transplant

On February 22, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, the Company’s lead product candidate (Press release, Bellicum Pharmaceuticals, FEB 22, 2016, View Source [SID:1234509128]).

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The FDA designation is for the combination of BPX-501 genetically modified T cells and activator agent rimiducid as "replacement T-cell therapy for the treatment of immunodeficiency and graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplant." BPX-501 is an adjunct T-cell therapy incorporating the Company’s proprietary CaspaCIDe safety switch.

Following an allogeneic transplant, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse. The ability to correct this immune deficiency through the add-back of mature donor T cells, without raising the risk of uncontrollable GvHD, has the potential to fundamentally change the risk profile of allogeneic transplantation.

"Expanding the availability of hematopoietic stem cell transplants to more patients with rare genetic diseases and blood cancers is a primary goal of our BPX-501 program," commented Tom Farrell, President and CEO of Bellicum Pharmaceuticals. "The FDA’s approval of our request for orphan drug designation is an important milestone that supports our efforts to address key risks and improve outcomes in allogeneic transplant which could make the procedure more viable for patients who lack a perfect match donor."

BPX-501 is currently being evaluated in multiple Phase 1/2 clinical trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the U.S. and Europe. Interim results presented at the 2015 ASH (Free ASH Whitepaper) Annual Meeting in pediatric patients with a variety of genetic diseases, including beta thalassemia, Wiskott-Aldrich and SCID, demonstrated disease-free outcomes following a haploidentical, T cell-depleted hematopoietic stem cell transplant, followed by an add-back of BPX-501 donor T cells. Results demonstrated reduced infection rates, faster immune reconstitution, and reductions in time to hospital discharge and in re-hospitalizations, compared to historical controls.

About Orphan Drug Designation

The FDA’s Office of Orphan Products Development (OOPD) provides orphan designation to drugs and biologics which are intended for the safe and effective treatment, diagnosis or prevention of rare diseases and disorders that affect fewer than 200,000 people in the U.S. Orphan designation also qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of seven years.

About BPX-501

BPX-501 is an adjunct T cell therapy of genetically modified donor T cells incorporating Bellicum’s proprietary CaspaCIDe safety switch. The product candidate is designed to provide a safety net to eliminate the BPX-501 alloreactive T cells should severe GvHD occur, enabling physicians to more safely perform haploidentical stem cell transplants by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.

Seattle Genetics Initiates Phase 1/2 Trial of Vadastuximab Talirine (SGN-CD33A) Combination Therapy for Patients with Untreated Myelodysplastic Syndrome (MDS)

On February 22, 2016 Seattle Genetics, Inc. (Nasdaq: SGEN) reported the initiation of a phase 1/2 clinical trial of vadastuximab talirine (SGN-CD33A; 33A) in combination with azacitidine (Vidaza) in patients with previously untreated myelodysplastic syndrome (MDS) (Press release, Seattle Genetics, FEB 22, 2016, View Source [SID:1234509127]).

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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. Azacitidine is a hypomethylating agent (HMA) commonly used in the treatment of MDS. MDS is known to be a precursor to acute myeloid leukemia (AML), and broadly expresses CD33.

"Most newly diagnosed patients with intermediate or high risk MDS are ineligible for allogeneic stem cell transplant due to age, comorbidities or lack of appropriate donor. For these patients, novel therapies are urgently needed to prolong survival and delay disease progression into AML," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "In our phase 1 AML clinical trial evaluating 33A plus HMAs (azacitidine or decitabine), we have observed encouraging tolerability and depletion of blasts from the bone marrow in many patients, and we recently presented preclinical data demonstrating synergistic activity of 33A plus HMAs. Expanding our clinical evaluation of 33A in MDS is part of a broad clinical development strategy to establish 33A as the foundation of care for patients with myeloid malignancies."

The phase 1/2, open-label, multi-center clinical trial is designed to evaluate the safety and activity of 33A administered in combination with azacitidine in patients with previously untreated International Prognostic Scoring System (IPSS) Intermediate-2 or high risk MDS. Phase 1 of the study will identify the recommended dose of 33A when combined with azacitidine in this patient population. The phase 2 portion of the trial will be a randomized, double-blind, placebo-controlled study evaluating azacitidine with or without 33A.

The primary endpoint in phase 1 is determination of the recommended 33A dose in combination with azacitidine. The primary endpoint in phase 2 is to compare the overall response rate between the two treatment arms. The secondary endpoints include evaluation of safety, best response, duration of response, progression-free survival and overall survival. The phase 1/2 trial will enroll approximately 130 patients at approximately 35 centers in North America.

In addition to this MDS trial, Seattle Genetics is evaluating 33A broadly across multiple lines of therapy in patients with AML, including the following ongoing trials:

A phase 1 trial of 33A monotherapy and in combination with HMAs in AML patients who have relapsed/declined intensive frontline therapy or are newly diagnosed;
A phase 1b trial in combination with standard of care intensive chemotherapy, including cytarabine and daunorubicin, for younger fit patients with AML; and,
A phase 1/2 trial in patients with relapsed or refractory AML evaluating 33A monotherapy as a pre-conditioning regimen prior to an allogeneic stem cell transplant and also for use as maintenance therapy following transplant.
Additionally, a phase 3 clinical trial to evaluate 33A in combination with HMAs in previously untreated older AML patients is planned to begin by the third quarter of 2016.

More information about SGN-CD33A and ongoing clinical trials can be found at www.ADC-CD33.com.

With more than 15 years of experience and innovation, Seattle Genetics is the leader in developing ADCs. ADCs are monoclonal antibodies that are designed to selectively deliver cell-killing agents to tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.

For more information about the trial, including enrolling centers, please visit www.clinicaltrials.gov.

About Myelodysplastic Syndrome

Myelodysplastic Syndromes (MDS) are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. MDS is often referred to as a "bone marrow failure disorder". MDS is a disorder that starts when abnormal progenitor cells in the bone marrow are damaged and have problems making new blood cells. Blood cells formed by the abnormal bone marrow cells are defective. Defective cells often have reduced survival and function, resulting in low blood counts and abnormal behavior. In advanced MDS, blasts are detectable in the bone marrow and usually express CD33. In about one-third of patients, MDS can progress to a rapidly growing cancer of the bone marrow cells called acute myeloid leukemia, or AML. According to the American Cancer Society, in 2016 more than 19,500 new cases of MDS will be diagnosed and more than 10,000 deaths will occur from MDS.

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 and MDS blast 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 in AML and MDS and a planned pivotal phase 3 clinical trial for patients with AML.