0001157523-13-003001.txt : 20130604 0001157523-13-003001.hdr.sgml : 20130604 20130604163013 ACCESSION NUMBER: 0001157523-13-003001 CONFORMED SUBMISSION TYPE: 8-K PUBLIC DOCUMENT COUNT: 4 CONFORMED PERIOD OF REPORT: 20130601 ITEM INFORMATION: Other Events ITEM INFORMATION: Financial Statements and Exhibits FILED AS OF DATE: 20130604 DATE AS OF CHANGE: 20130604 FILER: COMPANY DATA: COMPANY CONFORMED NAME: ARIAD PHARMACEUTICALS INC CENTRAL INDEX KEY: 0000884731 STANDARD INDUSTRIAL CLASSIFICATION: BIOLOGICAL PRODUCTS (NO DIAGNOSTIC SUBSTANCES) [2836] IRS NUMBER: 223106987 STATE OF INCORPORATION: DE FISCAL YEAR END: 1231 FILING VALUES: FORM TYPE: 8-K SEC ACT: 1934 Act SEC FILE NUMBER: 000-21696 FILM NUMBER: 13891675 BUSINESS ADDRESS: STREET 1: 26 LANDSDOWNE ST CITY: CAMBRIDGE STATE: MA ZIP: 02139 BUSINESS PHONE: 6174940400 MAIL ADDRESS: STREET 1: 26 LANDSDOWNE CITY: CAMBRIDGE STATE: MA ZIP: 02139 8-K 1 a50646076.htm ARIAD PHARMACEUTICALS, INC. 8-K

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

FORM 8-K

CURRENT REPORT
Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 1, 2013

ARIAD Pharmaceuticals, Inc.
(Exact name of registrant as specified in its charter)

Delaware

0-21696

22-3106987

(State or other jurisdiction

of incorporation)

(Commission

File Number)

(I.R.S. Employer

Identification No.)

26 Landsdowne Street, Cambridge, Massachusetts	02139
(Address of principal executive offices)	(Zip Code)

Registrant's telephone number, including area code: (617) 494-0400

Not Applicable
(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

⃞ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

⃞ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

⃞ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

⃞ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

ITEM 8.01 Other Events.

On June 1, 2013, ARIAD Pharmaceuticals, Inc. (the “Company”) issued the first of three press releases announcing data presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. This press release detailed the evaluation of the cardiovascular risk profile of Philadelphia-positive (Ph+) leukemia patients treated with Iclusig® (ponatinib) in the pivotal PACE trial. Serious arterial thrombotic (AT) events can be a complication of BCR-ABL tyrosine kinase inhibitor (TKI) therapy in Ph+ leukemias. In the single-arm, PACE trial, serious AT events, including cardiovascular, cerebrovascular and peripheral vascular events, occurred in 34 of 449 patients (8%). This analysis showed that patients who experienced serious ATs while on study more commonly had a history of pre-existing cardiac disease and a higher prevalence of baseline cardiovascular risk factors prior to enrollment than in those patients who did not experience these events. A copy of the press release is attached hereto as Exhibit 99.1 and is incorporated by reference into this Item 8.01 of this Current Report on Form 8-K.

On June 2, 2013, the Company issued a second press release on data presented at ASCO announcing long-term durability-of-response data from its Phase 1 trial of Iclusig® (ponatinib) in heavily pretreated patients with resistant or intolerant chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia. The study shows that among chronic-phase (CP) patients, the median durations of major and complete cytogenetic responses, along with major molecular response, have yet to be reached. The median follow-up for CP patients still on study is now more than three years (36.5 months). A copy of the press release is attached hereto as Exhibit 99.2 and is incorporated by reference into this Item 8.01 of this Current Report on Form 8-K.

On June 2, 2013, the Company issued a third press release on data presented at ASCO announcing clinical results on its investigational TKI, AP26113, in patients with advanced non-small cell lung cancer (NSCLC) from an ongoing Phase 1/2 trial. The study confirms compelling clinical evidence of the anti-tumor activity of AP26113 at multiple dose levels in patients with anaplastic lymphoma kinase positive NSCLC, including brain metastases, and initial clinical evidence of anti-tumor activity in patients with epidermal growth factor receptor mutant NSCLC. The study identified a recommended Phase 2 dose of 180 mg administered orally once daily. The Phase 2 portion of the trial is now open and enrolling patients at this dose in the first four expansion cohorts. A copy of the press release is attached hereto as Exhibit 99.3 and is incorporated by reference into this Item 8.01 of this Current Report on Form 8-K.

ITEM 9.01 Financial Statements and Exhibits

(d) The following exhibits are filed with this report:

Exhibit Number	Description

99.1	Press Release dated June 1, 2013.

99.2	Press Release dated June 2, 2013.

99.3	Press Release dated June 2, 2013.

The press releases contain hypertext links to information on our website and/or other websites. The information on our website and any other website is not incorporated by reference into this Current Report on Form 8-K and does not constitute a part of this Form 8-K.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

		ARIAD Pharmaceuticals, Inc.


		By:	/s/ Edward M. Fitzgerald
			Edward M. Fitzgerald
			Executive Vice President, Chief Financial Officer

Date:	June 4, 2013

EX-99.1 2 a50646076ex99_1.htm EXHIBIT 99.1

Exhibit 99.1

ARIAD Presents Analysis of Cardiovascular Risk Profile of Patients from Pivotal PACE Trial of Iclusig^® (Ponatinib)

CHICAGO & CAMBRIDGE, Mass.--(BUSINESS WIRE)--June 1, 2013--ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced results of evaluation of the cardiovascular risk profile of Philadelphia-positive (Ph+) leukemia patients treated with Iclusig^®(ponatinib) in the pivotal PACE trial. Serious arterial thrombotic (AT) events can be a complication of BCR-ABL tyrosine kinase inhibitor (TKI) therapy in Ph+ leukemias. In the single-arm, PACE trial, serious AT events, including cardiovascular, cerebrovascular and peripheral vascular events, occurred in 34 of 449 patients (8%). This analysis showed that patients who experienced serious ATs while on study more commonly had a history of pre-existing cardiac disease and a higher prevalence of baseline cardiovascular risk factors prior to enrollment than in those patients who did not experience these events.

The data are being featured today in a poster presentation at 8:00 a.m. (CT) and a poster discussion at 12:00 p.m. (CT) at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago.

Of 34 patients with serious AT events reported in the PACE trial, 21 had cardiovascular events and 14 had cerebrovascular or peripheral vascular events. Pre-existing cardiac disease was present in 15 of 21 patients (71%) who had cardiovascular events and 6 of 14 patients (43%) who had cerebrovascular or peripheral vascular events on study. Further, 30 patients (88%) had at least one pre-existing cardiovascular risk factor, 14 patients (41%) had pre-existing ischemic cardiac disease, and 19 patients (56%) were at least 65 years of age.

“Although uncommon, cardiovascular events have been reported in patients with Ph+ leukemias treated with BCR-ABL TKIs,” said H. Jean Khoury, M.D., professor of hematology and medical oncology, and director of the Division of Hematology of the Winship Cancer Institute at Emory University. “Patients in the PACE trial were heavily pretreated with multiple prior TKIs. This analysis shows that patients who experienced serious arterial thrombotic events generally were older, had a more prolonged duration of leukemia since original diagnosis, had one or more cardiovascular risk factors prior to entry in the trial and had a high prevalence of pre-existing cardiac and ischemic diseases.”

Methodology of PACE Trial Analysis

This analysis focuses on the subset of 34 patients with reported AT events considered serious adverse events. All adverse events presented are treatment-emergent adverse events.
Median follow-up for the total PACE trial patient population was 11 months (minimum, 9 months). This data set is the same as that described in the U.S. Prescribing Information for Iclusig.
AT events were categorized into three groups: cardiovascular, cerebrovascular and peripheral vascular according to the definitions of these groups used to prepare the U.S. Prescribing Information for Iclusig. The overall event rate was based on the summation of the individual disease definitions. A patient was classified as having an increase in blood pressure if a single recorded measurement of blood pressure had changed at any time during the course of the trial.
Analysis included assessment of the association between risk factors and occurrence of AT events. Cardiovascular risk factors included hypertension, elevated cholesterol, diabetes, and obesity. Additional demographic factors of age, gender (male), time since leukemia diagnosis, exposure to prior TKI therapy and history of cardiac disease were also assessed. Smoking was not included in the analysis, as data were not available.

Summary of Characteristics and Clinical Profile of Patients with Serious AT Events

Patients with serious AT events had significantly higher incidences of pre-existing diabetes (44% vs. 14%) and hypertension (82% vs. 51%) than patients who did not experience these events. Almost all patients who had cerebrovascular or peripheral vascular events while on study had hypertension at baseline.
Differences in demographics, medical history and previous therapy also distinguished the population experiencing serious AT events. History of ischemic cardiac disease (41% vs. 10%) and age of at least 65 years (56% vs. 33%) were significantly greater in those with serious AT events than in those without. The population also had a significantly longer duration of prior TKI therapy (6.3 vs. 4.9 years) and significantly longer duration of prior nilotinib therapy (1.8 vs. 1.2 years).
Patients from the serious AT group were exposed to comparable dose intensity of ponatinib when compared to those without serious AT events. The median time to onset of serious AT events was approximately six months. Blood pressure increased by one or two grades during the trial in 59% of patients who experienced serious AT events.
Patients were managed with dose interruption and dose modification comparably in patients with and without serious AT events. In more than one-third of patients with serious ATs, there was no modification to ponatinib dosing. Discontinuation rates among patients with serious AT events were comparable to the overall discontinuation rates for the study.
Anti-leukemic response to Iclusig was similar in patients with serious AT events as compared to those without (chronic-phase CML, 73% vs. 52%). Sixteen of 22 patients with serious AT events (73 %) achieved major cytogenetic response, and nine of 22 (41 %) had a major molecular response.

“This analysis is important as we consider the patient population now receiving Iclusig after becoming resistant or intolerant to prior TKI therapy and determine how to best treat patients with prior cardiovascular history or risk factors,” said Frank G. Haluska, M.D., Ph.D., senior vice president, clinical research and development and chief medical officer of ARIAD. “This analysis also showed that these patients can be managed with standard dose adjustments while maintaining clinical benefit from treatment. In Philadelphia-positive leukemia patients with predisposing factors or co-morbidities, physicians should pay close attention to management of hypertension and diabetes.”

About the PACE Trial

The FDA approval of Iclusig was based on results from the pivotal Phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial in patients with CML or Ph+ ALL who were resistant or intolerant to prior TKI therapy, or who had the T315I mutation of BCR-ABL. Iclusig had robust anti-leukemic activity, with 54 percent of chronic-phase CML patients, including 70 percent of patients with the T315I mutation, achieving a major cytogenetic response (MCyR) – the primary endpoint of the PACE trial for chronic-phase patients.

In patients with advanced disease, 52 percent of accelerated-phase CML patients, 31 percent of blast-phase CML patients and 41 percent of Ph+ ALL patients achieved a major hematologic response (MaHR) to Iclusig. MaHR was the primary endpoint in the trial for patients with advanced disease.

About Iclusig® (ponatinib)

Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, a common mutation which has been associated with resistance to other approved TKIs.

Indication, Usage and Dosing

Iclusig is indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to prior TKI therapy.

This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.

The recommended dose of Iclusig is a 45 mg tablet taken once-daily with or without food.

Important Safety Information

Boxed Warning

Arterial Thrombosis: Cardiovascular, cerebrovascular, and peripheral vascular thrombosis, including fatal myocardial infarction and stroke have occurred in Iclusig-treated patients. In clinical trials, serious arterial thrombosis occurred in 8% of Iclusig-treated patients. Interrupt and consider discontinuation of Iclusig in patients who develop arterial thrombotic events.

Hepatotoxicity: Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Iclusig for hepatotoxicity.

Warnings and Precautions

Congestive Heart Failure: Twenty patients treated with Iclusig (4%) experienced serious congestive heart failure (CHF) or left ventricular dysfunction (LVD), with 4 fatalities. Thirty-three patients treated with Iclusig (7%) experienced any grade of CHF or LVD. Monitor patients for signs or symptoms consistent with CHF and treat as clinically indicated, including interruption of Iclusig. Consider discontinuation of Iclusig in patients who develop serious CHF.

Hypertension: Eight patients treated with Iclusig (2%) experienced treatment-emergent symptomatic hypertension as a serious adverse reaction, including hypertensive crisis. Treatment-emergent hypertension (defined as systolic BP≥140 mm Hg or diastolic BP≥90 mm Hg on at least one occasion) occurred in 67% of patients (300/449). Monitor and manage blood pressure elevations.

Pancreatitis: Clinical pancreatitis occurred in 6% of patients (5% Grade 3) treated with Iclusig. The incidence of treatment emergent lipase elevation was 41%. Check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Dose interruption or reduction may be required. In cases where lipase elevations are accompanied by abdominal symptoms, interrupt treatment with Iclusig and evaluate patients for pancreatitis.

Hemorrhage: Serious bleeding events occurred in 5% (22/449) of patients treated with Iclusig, including fatalities. Hemorrhagic events occurred in 24% of patients. The incidence of serious bleeding events was higher in patients with AP-CML, BP-CML, and Ph+ ALL. Most events occurred in patients with grade 4 thrombocytopenia. Interrupt Iclusig for serious or severe hemorrhage.

Fluid Retention: Serious fluid retention events occurred in 3% of patients treated with Iclusig. One instance of brain edema was fatal. Monitor patients for fluid retention and manage patients as clinically indicated. Interrupt, reduce, or discontinue Iclusig as clinically indicated.

Cardiac Arrhythmias: Symptomatic bradyarrhythmias that led to a requirement for pacemaker implantation occurred in 3 (1%) Iclusig-treated patients. Advise patients to report signs and symptoms suggestive of slow heart rate (fainting, dizziness, or chest pain). Supraventricular tachyarrhythmias occurred in 5% of Iclusig-treated patients. Atrial fibrillation was the most common supraventricular tachyarrhythmia and occurred in 20 patients. For 13 patients, the event led to hospitalization. Advise patients to report signs and symptoms of rapid heart rate (palpitations, dizziness).

Myelosuppression: Severe (Grade 3 or 4) myelosuppression occurred in 48% (215/449) of patients treated with Iclusig. The incidence of these events was greater in patients with AP-CML, BP-CML and Ph+ ALL than in patients with CP-CML. Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated, and adjust the dose as recommended.

Tumor Lysis Syndrome: Two patients (<1%) with advanced disease (AP-CML, BP-CML, or Ph+ ALL) treated with Iclusig developed serious tumor lysis syndrome. Hyperuricemia occurred in 7% (30/449) of patients overall; the majority had CP-CML (19 patients). Ensure adequate hydration and treat high uric acid levels prior to initiating therapy with Iclusig.

Compromised Wound Healing and Gastrointestinal Perforation: Since Iclusig may compromise wound healing, interrupt Iclusig for at least 1 week prior to major surgery. Serious gastrointestinal perforation (fistula) occurred in one patient 38 days post-cholecystectomy.

Embryo-Fetal Toxicity: Iclusig can cause fetal harm. If Iclusig is used during pregnancy, or if the patient becomes pregnant while taking Iclusig, the patient should be apprised of the potential hazard to the fetus. Advise women to avoid pregnancy while taking Iclusig.

Adverse Reactions

The most common non-hematologic adverse reactions (≥20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia. Please see the full Prescribing Information for Iclusig, including the Boxed Warning.

About ARIAD

ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts and Lausanne, Switzerland, is an integrated global oncology company focused on transforming the lives of cancer patients with breakthrough medicines. ARIAD is working on new medicines to advance the treatment of various forms of chronic and acute leukemia, lung cancer and other difficult-to-treat cancers. ARIAD utilizes computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).

This press release contains “forward-looking statements” including, but not limited to, statements relating to the analysis of safety data for ponatinib. Forward-looking statements are based on management's expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, preclinical data and early-stage clinical data that may not be replicated in later-stage clinical studies, the costs associated with our research, development, manufacturing and other activities, the conduct, timing and results of pre-clinical and clinical studies of our product candidates, the adequacy of our capital resources and the availability of additional funding, and other factors detailed in the Company's public filings with the U.S. Securities and Exchange Commission. The information contained in this press release is believed to be current as of the date of original issue. The Company does not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in the Company's expectations, except as required by law.

CONTACT:
ARIAD Pharmaceuticals, Inc.
For Investors
Kendra Adams, 617-503-7028
Kendra.adams@ariad.com
or
For Media
Liza Heapes, 617-621-2315
Liza.heapes@ariad.com

EX-99.2 3 a50646076ex99_2.htm EXHIBIT 99.2

Exhibit 99.2

ARIAD Announces Long-Term Durability-of-Response Data on Ponatinib from Ongoing Phase 1 Study

Median follow-up of more than three years for chronic-phase CML patients

72 percent of patients maintain major cytogenetic response; median duration not yet reached

CHICAGO & CAMBRIDGE, Mass.--(BUSINESS WIRE)--June 2, 2013--ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced long-term durability-of-response data from its Phase 1 trial of Iclusig^® (ponatinib) in heavily pretreated patients with resistant or intolerant chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The study shows that among chronic-phase (CP) patients, the median durations of major and complete cytogenetic responses, along with major molecular response, have yet to be reached. The median follow-up for CP patients still on study is now more than three years (36.5 months).

These data are being featured today at 8:00 a.m. CT in a poster presentation at the Annual Meeting of the American Society of Clinical Oncology (ASCO) being held in Chicago.

“These data show that ponatinib continues to provide deep, durable clinical responses in chronic-phase CML patients who failed several prior tyrosine kinase inhibitor therapies,” stated Michael Mauro, M.D., associate professor at the Oregon Health & Science University, Portland, Oregon. “It is noteworthy that these patients are maintaining their responses over this long period of time and that a median duration of response to ponatinib has not yet been reached.”

Phase 1 Long-Term Update

The Phase 1 dose-escalation study of ponatinib enrolled 81 patients with resistant or refractory hematologic cancers, including 43 patients with chronic-phase CML. Sixty-one percent of the CP-CML patients in this study had failed at least three prior tyrosine kinase inhibitors (TKI).

The trial is ongoing, and study data reported at ASCO show deep and durable anti-leukemic activity in CP-CML patients.

With a median follow-up of 36.5 months, 28 of the 43 patients with CP-CML remain on study (65%). Of these, 23 are currently in major cytogenetic response (MCyR), 22 in complete cytogenetic response (CCyR), and 17 in major molecular response (MMR) or greater.

The median time to MCyR among responders was 2.8 months (range, 1.8 to 16.6 months). The duration of MCyR ranged from 1.9 to more than 46.5 months (ongoing); the median has not yet been reached.
The median time to CCyR among responders was 5.5 months (range, 1.8 to 33.2 months). The duration of CCyR ranged from 1.9 to more than 40.5 months (ongoing); the median has not yet been reached.

The median time to MMR was 5.6 months (range, 1.8 to 38.7 months). The duration of MMR ranged from 2.8 to more than 41 months (ongoing); the median has not yet been reached. Of the 17 patients remaining on trial in MMR, 7 have achieved the deeper response landmark of MR4 and an additional 6 have achieved MR4.5.
The most common non-hematologic treatment-related adverse events among all patients in this trial included rash (42%), arthralgia (20%), increased lipase (20%), fatigue (20%) and dry skin (19%), with the majority of these being grades 1 or 2 in severity. The most common hematologic treatment-related adverse events included thrombocytopenia (34%), neutropenia (14%) and anemia (12%), with thrombocytopenia and neutropenia being primarily grades 3 or 4 in severity.

“In addition to ponatinib achieving robust patient responses in this refractory CML population, responses are deepening over time, with nearly all responding patients in CCyR and more than half of the responders showing deep molecular responses,” stated Frank G. Haluska, M.D., Ph.D., senior vice president and chief medical officer at ARIAD.

About CML and Ph+ ALL

CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase and blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. The BCR-ABL protein is expressed in both of these diseases.

About Iclusig (ponatinib)

Indication, Usage and Dosing

This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.

The recommended dose of Iclusig is a 45 mg tablet taken once-daily with or without food.

Important Safety Information

Boxed Warning

Warnings and Precautions

Tumor Lysis Syndrome: Two patients (<1%) with advanced disease (AP-CML, BP-CML, or Ph+ ALL) treated with Iclusig developed serious tumor lysis syndrome. Hyperuricemia occurred in 7%(30/449) of patients overall; the majority had CP-CML (19 patients). Ensure adequate hydration and treat high uric acid levels prior to initiating therapy with Iclusig.

Adverse Reactions

About ARIAD

This press release contains “forward-looking statements” including, but not limited to, statements relating to the updated clinical data and durability of response for ponatinib. Forward-looking statements are based on management's expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, preclinical data and early-stage clinical data that may not be replicated in later-stage clinical studies, the costs associated with our research, development, manufacturing and other activities, the conduct, timing and results of pre-clinical and clinical studies of our product candidates, the adequacy of our capital resources and the availability of additional funding, and other factors detailed in the Company's public filings with the U.S. Securities and Exchange Commission. The information contained in this press release is believed to be current as of the date of original issue. The Company does not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in the Company's expectations, except as required by law.

CONTACT:
ARIAD Pharmaceuticals, Inc.
For Investors
Kendra Adams, 617-503-7028
Kendra.adams@ariad.com
or
For Media
Liza Heapes, 617-621-2315
Liza.heapes@ariad.com

EX-99.3 4 a50646076ex99_3.htm EXHIBIT 99.3

Exhibit 99.3

ARIAD Presents Updated Phase 1 Data on AP26113 in Patients with Non-Small Cell Lung Cancer

~ Phase 2 Trial of AP26113 Now Enrolling Patients

~Investor Meeting and Webcast on Monday, June 3 at 7:30 a.m. CT

CHICAGO & CAMBRIDGE, Mass.--(BUSINESS WIRE)--June 2, 2013--ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced updated clinical results on its investigational tyrosine kinase inhibitor (TKI), AP26113, in patients with advanced non-small cell lung cancer (NSCLC) from an ongoing Phase 1/2 trial. The study confirms compelling clinical evidence of the anti-tumor activity of AP26113 at multiple dose levels in patients with anaplastic lymphoma kinase positive (ALK+) NSCLC, including brain metastases, and initial clinical evidence of anti-tumor activity in patients with epidermal growth factor receptor mutant (EGFRm) NSCLC.

The study identified a recommended Phase 2 dose of 180 mg administered orally once daily. The Phase 2 portion of the trial is now open and enrolling patients at this dose in the first four expansion cohorts. Further Phase 1 evaluation of the 240 mg dose is continuing in NSCLC patients with documented EGFRm and the secondary mutation, T790M, following disease progression on prior EGFR TKI therapy.

The Phase 1 results are being presented this morning at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago.

Phase 1 Study Design

Patients enrolled in the Phase 1 portion of the trial had advanced solid tumors that were refractory to available therapies or had no standard or curative treatment available. The objectives of the Phase 1 portion of the trial were to determine the recommended dose for further study of AP26113 and to characterize its safety (including the maximum tolerated dose, MTD), pharmacokinetics, and preliminary anti-tumor activity. The trial used an open-label, dose-escalating design. Anti-tumor activity was determined by serial CT scans using RECIST criteria.

Fifty-five patients were enrolled in the study at seven dose levels (i.e., 30, 60, 90, 120, 180, 240 and 300 mg per day, administered orally). Six patients received twice-a-day (BID) dosing. Twenty-two patients currently remain on study.

Forty-seven of the patients enrolled in the study to date have NSCLC, including 24 who are ALK+ and 19 who are EGFRm. Two-thirds of these patients failed three or more regimens of prior systemic anti-tumor treatment, including both targeted therapies and chemotherapy.

“Results from this ongoing trial confirm that AP26113 has promising anti-tumor activity in patients with ALK+ NSCLC and other ALK+ tumors, including brain metastases in these patients,” stated D. Ross Camidge, M.D., Ph.D. Associate Professor of Medicine at University of Colorado School of Medicine, the study’s presenter at ASCO. “Additionally, initial objective evidence of anti-tumor activity has been demonstrated in a patient with EGFR-mutant lung cancer.”

Key data from the study presented at ASCO include:

Safety and Tolerability

Safety assessments show AP26113 to be well tolerated. The most common adverse events (AEs), regardless of treatment relationship and including all grades, were fatigue (40%) and nausea (36%). The only treatment-related AEs that occurred in at least 10% of study patients were nausea (33%), fatigue (22%), and diarrhea (20%).
Serious AEs (regardless of treatment relationship) were uncommon. Events occurring in two or more patients were: pneumonia (7%), cough (4%), dyspnea (4%), hypoxia (4%), and pleural effusion (4%). No signs of rash that would be considered typical of EGFR inhibitors were seen at any doses studied.
There were two patients with a reported dose-limiting toxicity (DLT). One patient experienced elevated alanine aminotransferase (ALT), a liver enzyme, at 240 mg per day; the event resolved, and the patient remains on study. A separate patient experienced dyspnea (shortness of breath) and hypoxia (reduction of oxygen supply) at 300 mg per day. This patient discontinued from the study.

Additionally, isolated events of dyspnea and hypoxia were observed during initial dose-cohort expansions at 120 mg and 180 mg per day. In one case at 180 mg per day, the event occurred after one dose of AP26113 in a patient who subsequently died. The cause of death was adenocarcinoma of the lung, extremely widely metastatic to both lungs; the investigator thought AP26113 may have been a contributory factor. As a result, lower dose cohorts (90 mg, 120 mg, and 180 mg, including BID dosing) were expanded using modified eligibility criteria, and no further AEs of this nature were observed in any of the more recently enrolled patients (N = 14).

ALK+ Patients

Objective responses were observed in ALK+ NSCLC patients at the lowest dose tested (60 mg), and responses were observed in patients who were either naïve or resistant to crizotinib (Xalkori^®) – the currently available first-generation ALK inhibitor.
Of the 24 ALK+ patients evaluable for response, 15 (63%) demonstrated an objective response, including 14 partial responses (PR) and one complete response (CR). Of the 16 crizotinib-resistant NSCLC patients, 12 (75%) treated with AP26113 demonstrated a PR. Of the two crizotinib-naïve NSCLC patients, one treated with AP26113 demonstrated a CR. Objective-response durations ranged from 3 months to 9 months, with responses in 10 of the 15 patients (67%) ongoing. The “waterfall plot” analysis demonstrated tumor shrinkage in nearly all ALK+ patients.
Of particular note, four out of five ALK+ patients had a response in pre-existing brain metastases, and all four remain on study, with the longest duration of 6 months. This includes one ALK+ patient who was crizotinib-resistant and also resistant to the investigational agent LDK378.

EGFRm Patients

Of the 20 patients who had a history of EGFRm, 18 were evaluable for response. Ten EGFRm patients had a history of a T790M secondary mutation during or after prior erlotinib (Tarceva^®) therapy and had also failed rounds of chemotherapy, targeted therapy, and/or other investigational agents.

Of the 18 evaluable patients, one EGFRm patient (EGFR exon-19 deletion by history, T790M status unknown) achieved a PR and remains on study (duration, 6 months), and seven patients had stable disease (SD).
Of the 10 patients with a history of a T790M secondary mutation, four patients had SD on AP26113, with durations ranging from 2 months to 9 months, and one SD is ongoing (duration, 4 months).
Three of the 10 T790M patients had their T790M status documented during or after their most recent EGFR TKI, and had EGFR TKI as their last therapy prior to receiving AP26113 (with an intervening period of more than one month). Two of these patients had SD on AP26113, and the third discontinued prior to receiving a follow-up scan.

Pharmacokinetics and Dose Selection

Pharmacokinetic data indicate that the median plasma levels at doses of 180 mg and 240 mg once daily remain above the IC50 values determined pre-clinically for inhibition of ALK, c-ros oncogene-1 (ROS1) and EGFRm, and their secondary resistance mutations, for the entire 24 hour dosing period.
The MTD has not been identified. Based on safety, efficacy, and pharmacokinetic data, the recommended Phase 2 dose for ALK+, ROS1+ and EGFRm patients is 180 mg once daily. This dose will be used in the Phase 2 portion of the ongoing Phase 1/2 trial and in the pivotal trial of AP26113 in patients who are ALK+ NSCLC patients who are crizotinib-resistant.
In parallel, further Phase 1 testing at the 240 mg dose level is underway in patients with documented EGFRm T790M secondary mutation, following disease progression on prior EGFR TKI therapy, potentially supporting further dose escalation in individual patients.

Phase 2 Portion of Trial Now Enrolling Patients

The Phase 2 portion of the ongoing Phase 1/2 clinical trial is now enrolling patients at nine sites in the United States and Europe. The Phase 2 portion of the trial consists of five expansion cohorts: (1) ALK+ treatment naïve NSCLC, (2) ALK+ resistant to crizotinib NSCLC, (3) EGFRm resistant to one prior EGFR TKI with documented T790M NSCLC, (4) ROS1+ NSCLC and other targets, and (5) ALK+, either naïve or resistant to crizotinib, NSCLC with active brain metastases. This fifth expansion cohort will begin enrolling patients in the third quarter of 2013.

Cohort 3 in the Phase 2 portion of the ongoing study is enrolling patients with T790M-mediated resistance to one prior EGFR TKI. Patients will have a documented T790M secondary mutation of EGFR following disease progression on the most recent course of EGFR TKI therapy, and will have stopped that therapy within 30 days prior to initiating AP26113. No intervening therapy prior to starting AP26113 will be permitted.

“We believe AP26113 will be a compelling new medicine for patients with ALK-positive lung cancer and look forward to evaluating AP26113 in a rigorously defined EGFRm patient population with T790M-mediated resistance in the Phase 2 portion of the ongoing clinical trial,” stated Frank G. Haluska, M.D., Ph.D., senior vice president of clinical research and development and chief medical officer at ARIAD. “In parallel to enrollment in the Phase 2 expansion cohorts, we plan to begin a pivotal trial of AP26113 in ALK-positive NSCLC patients who are resistant to crizotinib in the third quarter of 2013.”

Investor and Analyst Briefing and Webcast

A breakfast meeting to review the most recent clinical data from the Phase 1 portion of the ongoing Phase 1/2 clinical trial of AP26113 with research analysts and institutional investors will feature Scott Gettinger, M.D., Associate Professor of Medicine at Yale School of Medicine and members of ARIAD’s management. This meeting will be webcast live along with presentation slides and can be accessed by visiting the investor relations section of the Company’s website at http://investor.ariad.com.

A replay of this investor event will be available on the ARIAD website approximately three hours after the presentation and will be archived for three weeks.

About ARIAD

Xalkori^® is a registered trademark of Pfizer, Inc. Tarceva^® is a registered trademark of Astellas Pharma US, Inc.

This press release contains “forward-looking statements” including, but not limited to, statements relating to preclinical and clinical data for AP26113. Forward-looking statements are based on management's expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, preclinical data and early-stage clinical data that may not be replicated in later-stage clinical studies, the costs associated with our research, development, manufacturing and other activities, the conduct, timing and results of pre-clinical and clinical studies of our product candidates, the adequacy of our capital resources and the availability of additional funding, and other factors detailed in the Company's public filings with the U.S. Securities and Exchange Commission. The information contained in this press release is believed to be current as of the date of original issue. The Company does not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in the Company's expectations, except as required by law.

CONTACT:
ARIAD Pharmaceuticals, Inc.
For Investors
Kendra Adams, 617-503-7028
Kendra.adams@ariad.com
or
For Media
Liza Heapes, 617-621-2315
Liza.heapes@ariad.com