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PDL BioPharma Completes Royalty Transaction with ARIAD Pharmaceuticals

On July 29, 2015 PDL BioPharma, Inc. (NASDAQ: PDLI) reported that it has entered into a revenue interest assignment agreement (the "Agreement") in which it has agreed to provide ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) with up to $200 million in revenue interest financing in exchange for royalties on the net revenues of Iclusig (ponatinib). Funding of the first $100 million will be made in two tranches of $50 million each, with the initial amount having already been funded on the closing date of the agreement and an additional $50 million to be funded on the 12-month anniversary of the closing date. In addition, ARIAD has an option to draw up to an additional $100 million at any time between the sixth and twelfth month anniversaries of the closing date.
PDL will initially receive 2.5% of the worldwide net revenues of Iclusig until the one year anniversary of the closing date, at which time the royalty increases to 5.0% of the worldwide net revenues of Iclusig and remains until December 31, 2018. Beginning January 1, 2019 and thereafter, the royalty rate will increase to 6.5%, subject to an additional increase to 7.5% if PDL’s funding exceeds $150 million. If PDL does not receive payments equal to or greater than the total amount funded on or before the fifth anniversary of each of the respective fundings, ARIAD will pay PDL the difference between the amounts funded by PDL and the amounts paid to such date. PDL has a put option based upon certain events and ARIAD has a call option to repurchase the revenue interest at any time. Both the put and call prices have been pre-determined.

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"We are extremely pleased to be able to structure a flexible, customized financial agreement that provides ARIAD with capital to support its key products," stated John P. McLaughlin, president and chief executive officer of PDL BioPharma.

"We are pleased to collaborate with PDL as we begin the next phase of our company’s growth with the initiation of a front-line trial of brigatinib and plans for its commercialization, along with continued commercialization of Iclusig," said Dr. Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. "Furthermore, this agreement provides ARIAD with the flexibility needed for future financing and business development activity."

About Iclusig (ponatinib)
Iclusig is approved in the U.S., EU, Australia, Israel, Canada and Switzerland.

In the U.S., Iclusig is a kinase inhibitor indicated for the:
Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acutelymphoblastic leukemia (Ph+ ALL).
Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.

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

Foundation Medicine Announces 2015 Second Quarter Results and Recent Highlights

On July 29, 2015 Foundation Medicine, Inc. (NASDAQ:FMI) reported financial and operating results for its second quarter ended June 30, 2015 (Press release, Foundation Medicine, JUL 29, 2015, View Source [SID:1234506738]). Highlights for the quarter included:

8,846 clinical tests reported in the second quarter, 50% year-over-year growth;

Second quarter revenue of $22.5 million, 55% year-over-year growth;

Second quarter revenue from biopharmaceutical customers of $10.0 million, 97% year-over-year growth;

FoundationCORE molecular information knowledgebase grew to over 50,000 patient cases;

Updated full-year 2015 revenue guidance to a range of $85 to $95 million, and full-year 2015 reported clinical test volumes to a range of 35,000 to 38,000.

Foundation Medicine reported total revenue of $22.5 million in the second quarter of 2015, compared to $14.5 million in the second quarter of 2014 and $19.3 million in the first quarter of 2015. Revenue from clinical testing in the second quarter of 2015 was $12.4 million, compared to $9.4 million in the second quarter of 2014 and $11.1 million in the first quarter of 2015.

The company reported 8,846 clinical tests in the second quarter of 2015, a 50% increase from the same quarter last year and a 13% increase from this year’s first quarter. This number includes 7,809 FoundationOne tests and 1,037 FoundationOne Heme tests. The results of an additional 1,451 tests were also reported to biopharmaceutical customers in this year’s second quarter.

Revenue from biopharmaceutical customers grew to $10.0 million in the second quarter, a 97% increase from the same quarter last year and an increase of 22% from the first quarter of 2015. This growth underscores the diversification of revenue generating activities provided to the company’s biopharmaceutical customers across clinical trial support, molecular information data access, and companion diagnostic development support.

"Foundation Medicine delivered 16% quarter-over-quarter revenue growth demonstrating that our commercial team continues to leverage a portfolio of differentiated products for both our clinical and biopharmaceutical clients and partners," said Michael Pellini, M.D., chief executive officer of Foundation Medicine. "That said, our clinical volume growth was affected by slower than anticipated progress towards obtaining a local coverage determination from our regional Medicare Administrative Contractor (MAC) and by some competitive noise in the market. As a result, we are adjusting guidance for clinical volume and annual revenues. We remain focused on building and investing in this business to deliver growth and value creation by integrating our molecular information products into routine patient care."

The company’s cancer knowledgebase, FoundationCORE, grew to more than 50,000 clinical cases. FoundationCORE is a unique asset and critical component of the value that Foundation Medicine delivers to both its biopharmaceutical and physician customers. The increasing scale and breadth of a high quality, clinically relevant oncology data set derived from the company’s analytically validated testing platform continues to enhance clinical practice and enable improved outcomes for patients.

Total operating expenses for the second quarter of 2015 were approximately $46.6 million, but included a one-time expense of $14.4 million in advisor fees related to the closing of our strategic collaboration with Roche, compared with $21.6 million for the second quarter of 2014. Net loss was approximately $33.1 million in the second quarter of 2015, or a $0.98 loss per share. Adjusted for this same one-time advisor fee expense in the second quarter, net loss was approximately $18.7 million. At June 30, 2015, the company held $264 million in cash and cash equivalents.

Recent Enterprise Highlights

Foundation Medicine announced the initiation of a large, multi-center clinical study to validate and support the anticipated commercial launch of its novel, circulating tumor DNA (ctDNA) assay to advance precision medicine in oncology.

HealthChoice Oklahoma and one additional regional payer in Southern California each enacted broad, pan-cancer coverage policies for FoundationOne and FoundationOne Heme for their members.

Palmetto GBA, a Medicare Administrative Contractor (MAC) with expertise in molecular diagnostics, issued a final local coverage determination on July 6th for comprehensive genomic profiling in a subset of patients with non-small cell lung cancer.
In June, Foundation Medicine and IMS Health announced a collaboration to advance the understanding and effectiveness of precision medicine for treating cancer. The collaboration associates claims, electronic medical records and biomarker data at the anonymized patient level with FoundationCORE to improve cancer care by better connecting patients to the right targeted therapies at the right time.

In June, Foundation Medicine and its collaborators presented 22 oral and poster presentations at the 2015 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, including promising clinical outcomes underscoring the importance of integrating comprehensive genomic profiling into clinical oncology care.

In May, new clinical data presented at the 3rd Biennial Pediatric Neuro-Oncology Basic and Translational Research Conference demonstrated that FoundationOne identified a high frequency of clinically relevant genomic alterations in pediatric gliomas that informed treatment decisions and, in some, cases, resulted in promising outcomes.

2015 Outlook

The company expects to report between 35,000 and 38,000 clinical tests in 2015.

The company anticipates 2015 revenue will be in the range of $85 to $95 million.

The company expects operating expenses in the range of $128 to $138 million, plus an additional $14.4 million one-time advisor fee expense recognized in the second quarter related to the closing of the Roche strategic collaboration.

The company expects to launch a circulating tumor DNA (ctDNA) test for its biopharmaceutical partners by year-end, and a commercial ctDNA assay for clinical testing in 2016.

Advaxis’s Scientific Founder to Present on ADXS-HER2 at World Congress on Breast Cancer 2015

On July 29, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported that the company’s scientific founder, Yvonne Paterson, Ph.D., Professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania, will give a presentation titled "HER-2/neu as a target for Listeria-based cancer immunotherapy for breast cancer" on Tuesday, August 4 at 9:00 a.m. BST, at the 2015 World Congress on Breast Cancer in Birmingham, UK (Press release, Advaxis, JUL 29, 2015, View Source [SID:1234506737]).

"I’ve dedicated over 20 years of work to the application of Listeria monocytogenes in targeted tumor-associated antigens," said Dr. Paterson. "I am thankful for the opportunity to showcase the success of this process in HER2 expressing breast cancers."

The presentation, which is scheduled to take place during the symposium on "Immunotherapy of Breast Cancer," will highlight pre-clinical research findings with Advaxis’s Lm Technology immunotherapy ADXS-HER2 which show promise for limiting tumor growth in HER2 expressing cancers, such as breast cancer. In clinical trials to date in multiple tumor types, Advaxis’s Lm Technology immunotherapies have been well-tolerated and have demonstrated anti-tumor activity, including prolonged survival, stable disease and, in some cases, complete or partial remission. In addition, preliminary data have demonstrated ADXS-HER2, in combination with palliative radiation, delayed tumor progression and prolonged overall survival in a group of 12 pet dogs with treatment-naïve spontaneous canine osteosarcoma.

"We are appreciative of the astounding work Dr. Paterson has done in the area of Lm Technology," said Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. "Her scientific research has been instrumental in bringing about the first human trial of ADXS-HER2 in locally advanced/metastatic HER2 expressing solid tumors, which is scheduled to commence enrollment this summer."

Advaxis recently announced the United States Patent and Trademark Office (USPTO) granted a patent expanding Advaxis’s intellectual property portfolio in claiming numerous compositions for the development of ADXS-HER2 in HER2 expressing cancers.

About HER2 Expressing Cancers

Human epidermal growth factor receptor 2 (HER2) is expressed in a percentage of solid tumors such as breast, gastric, bladder, brain, pancreatic, ovarian and osteosarcoma. The American Cancer Society estimates that in 2015 in the United States alone there will be 231,840 new cases of invasive breast cancer; 24,590 new cases of gastric cancer; 74,000 new cases of bladder cancer; 22,850 new cases of brain/spinal cancer; 48,960 new cases of pancreatic cancer; 21,290 new cases of ovarian cancer; and 800 new cases of osteosarcoma. HER2 expression is associated with more aggressive disease, increased risk of relapse and decreased overall survival, and is an important target for immunotherapy.

About ADXS-HER2

ADXS-HER2 is an Lm Technology immunotherapy product candidate being developed by Advaxis for the targeted treatment of HER2 expressing cancers. ADXS-HER2 received orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of osteosarcoma in May 2014. Advaxis is developing ADXS-HER2 for both human and animal-health, and has seen encouraging data in canine osteosarcoma, which is considered a model for human osteosarcoma. Advaxis licensed ADXS-HER2 and three other immunotherapy constructs to Aratana Therapeutics, Inc. for pet therapeutics.

Aeterna Zentaris Announces Optimized Erk Inhibitor Compounds For Further Development

On July 29, 2015 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") reported it has selected an optimized Erk inhibitor molecule for development, thus achieving another important milestone in the development of a new class of potential cancer therapies (Press release, AEterna Zentaris, JUL 29, 2015, View Source [SID:1234506752]).

The MAPK pathway represents a prime target for therapeutic intervention in cancer. Recently approved compounds demonstrate significant antitumor activities and survival benefits for B-Raf and Mek inhibitors. Erk inhibitors may be preferred agents in tumors with aberrant MAPK pathway activity, e.g. in tumors with mutated or wildtype B-Raf, mutated or wildtype ras, and in tumors with acquired resistance to Raf and Mek inhibitors.

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At the 2014 American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s annual meeting, the Company presented an abstract of its work on an Erk inhibitor molecule called "AEZS-134". The abstract was selected by participants in the meeting as one of the 11 high-impact abstracts out of hundreds presented on the topic. Subsequently to this recognition, the Company continued its efforts on the Erk inhibitor program, including identification of an optimized molecule.

An optimized Erk inhibitor compound, AEZS-140, and back-up candidates were identified as a result of the development efforts. AEZS-140 and the back-up candidates demonstrate improved plasma exposure in rodents as well as enhanced anti-tumor efficacy in comparison to the previous lead compound, AEZS-134. Furthermore, AEZS-140 was profiled against several clinical Raf, Mek and Erk inhibitors and demonstrated very competitive activity.

The Company will proceed with the next development steps for AEZS-140 and the back-up compounds, including in depth profiling in vitro and, also, further in vivo tumor models. The Company is seeking proposals from parties who are interested in either co-developing or licensing the compounds.

David A. Dodd, Chairman and CEO of Aeterna Zentaris, commented, "Our strategy includes leveraging some of our promising early-stage drug candidates in order to generate potential long-term value without having to invest in their development. We are pursuing this strategy with respect to our Erk inhibitor development program. A therapeutic agent arising from this program could represent a novel approach to treating types of cancers with acquired resistance to Raf and Mek inhibitors. Our business development team is already engaged in discussions with parties who have previously expressed an interest in our work with Erk inhibitors."

Kyowa Hakko Kirin and Bristol-Myers Squibb Announce Immuno-Oncology Clinical Collaboration Studying Mogamulizumab and Opdivo (nivolumab) in Advanced Solid Tumors in the U.S.

On July 29, 2015 Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151,"Kyowa Hakko Kirin") and Bristol-Myers Squibb Company (NYSE:BMY, "Bristol-Myers Squibb") reported that the companies have entered into a clinical trial collaboration agreement to conduct a Phase 1/2 combination study with mogamulizumab, an anti-CCR4 antibody and Opdivo (nivolumab), a PD-1 immune checkpoint inhibitor (Press release, Bristol-Myers Squibb, JUL 29, 2015, View Source [SID:1234506746]).

The study, which will be conducted in the U.S., will focus on evaluating the safety, tolerability and anti-tumor activity of combining mogamulizumab and Opdivo as a potential treatment option for patients with advanced or metastatic solid tumors. Prior to this agreement, Kyowa Hakko Kirin, Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. (Tokyo: 4528) entered into a clinical trial collaboration agreement to study the combination of mogamulizumab and Opdivo in Japan.

Mogamulizumab and Opdivo are part of a new class of cancer treatments known as immunotherapies, which are designed to harness the body’s own immune system in fighting cancer by targeting distinct regulatory components of the immune system.

"We are pleased to conduct a combination study with Bristol-Myers Squibb not only in Japan but also in the U.S.," said Yoichi Sato, Director of the Board Managing Executive Officer, Vice President, Head of Research and Development Division of Kyowa Hakko Kirin. "We believe that the planned combination of these two immunotherapies has the potential to deliver better outcomes in patients with advanced cancers than existing treatments."

"Today’s agreement builds on our initial collaboration with Kyowa Hakko Kirin in Japan, which includes our partner Ono Pharmaceutical Co., Ltd., and is the latest example of our continued commitment to evaluating the potential of combination immuno-oncology regimens for patients with metastatic cancer," stated Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb.

The study will be conducted by Kyowa Hakko Kirin. Additional details of the collaboration were not disclosed.

About Mogamulizumab

Mogamulizumab (Brand name: POTELIGEO) is a novel, humanized mAb directed against CC chemokine receptor type 4 (CCR4). Engineered by Kyowa Hakko Kirin’s unique POTELLIGENT Technology, the antibody is designed to kill its target cells through potent antibody-dependent cellular cytotoxicity. Mogamulizumab was launched in Japan in May 2012 for the treatment of patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma (ATL). The drug was approved for indication expansion and was granted marketing authorization in Japan for the treatment of patients with relapsed or refractory CCR4-positive, peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) in March 2014, and with chemotherapy-native CCR4-positive ATL in December 2014. Clinical trials with mogamulizumab are ongoing in the US, EU and other countries.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that has received approval from the U.S. Food and Drug Administration (FDA) as a monotherapy in two cancer indications. On March 5, 2015, Opdivo received FDA approval for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

In the U.S., Opdivo is also indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Opdivo became the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide.

IMPORTANT SAFETY INFORMATION

Immune-Mediated Pneumonitis

Severe pneumonitis or interstitial lung disease, including fatal cases, occurred with OPDIVO treatment. Across the clinical trial experience in 691 patients with solid tumors, fatal immune-mediated pneumonitis occurred in 0.7% (5/691) of patients receiving OPDIVO; no cases occurred in Trial 1 or Trial 3. In Trial 1, pneumonitis, including interstitial lung disease, occurred in 3.4% (9/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Immune-mediated pneumonitis occurred in 2.2% (6/268) of patients receiving OPDIVO; one with Grade 3 and five with Grade 2. In Trial 3, immune-mediated pneumonitis occurred in 6% (7/117) of patients receiving OPDIVO, including, five Grade 3 and two Grade 2 cases. Monitor patients for signs and symptoms of pneumonitis. Administer corticosteroids for Grade 2 or greater pneumonitis. Permanently discontinue OPDIVO for Grade 3 or 4 and withhold OPDIVO until resolution for Grade 2.

Immune-Mediated Colitis

In Trial 1, diarrhea or colitis occurred in 21% (57/268) of patients receiving OPDIVO and 18% (18/102) of patients receiving chemotherapy. Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving OPDIVO; five with Grade 3 and one with Grade 2. In Trial 3, diarrhea occurred in 21% (24/117) of patients receiving OPDIVO. Grade 3 immune-mediated colitis occurred in 0.9% (1/117) of patients. Monitor patients for immune-mediated colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO for Grade 2 or 3. Permanently discontinue OPDIVO for Grade 4 colitis or recurrent colitis upon restarting OPDIVO.

Immune-Mediated Hepatitis

In Trial 1, there was an increased incidence of liver test abnormalities in the OPDIVO-treated group as compared to the chemotherapy-treated group, with increases in AST (28% vs 12%), alkaline phosphatase (22% vs 13%), ALT (16% vs 5%), and total bilirubin (9% vs 0). Immune-mediated hepatitis occurred in 1.1% (3/268) of patients receiving OPDIVO; two with Grade 3 and one with Grade 2. In Trial 3, the incidences of increased liver test values were AST (16%), alkaline phosphatase (14%), ALT (12%), and total bilirubin (2.7%). Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4 immune-mediated hepatitis.

Immune-Mediated Nephritis and Renal Dysfunction

In Trial 1, there was an increased incidence of elevated creatinine in the OPDIVO-treated group as compared to the chemotherapy-treated group (13% vs 9%). Grade 2 or 3 immune-mediated nephritis or renal dysfunction occurred in 0.7% (2/268) of patients. In Trial 3, the incidence of elevated creatinine was 22%. Immune-mediated renal dysfunction (Grade 2) occurred in 0.9% (1/117) of patients. Monitor patients for elevated serum creatinine prior to and periodically during treatment. For Grade 2 or 3 serum creatinine elevation, withhold OPDIVO and administer corticosteroids; if worsening or no improvement occurs, permanently discontinue OPDIVO. Administer corticosteroids for Grade 4 serum creatinine elevation and permanently discontinue OPDIVO.

Immune-Mediated Hypothyroidism and Hyperthyroidism

In Trial 1, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of patients receiving OPDIVO and 1% (1/102) of patients receiving chemotherapy. In Trial 3, hypothyroidism occurred in 4.3% (5/117) of patients receiving OPDIVO. Hyperthyroidism occurred in 1.7% (2/117) of patients, including one Grade 2 case. Monitor thyroid function prior to and periodically during treatment. Administer hormone replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism.

Other Immune-Mediated Adverse Reactions

In Trial 1 and 3 (n=385), the following clinically significant immune-mediated adverse reactions occurred in <2% of OPDIVO-treated patients: adrenal insufficiency, uveitis, pancreatitis, facial and abducens nerve paresis, demyeliniation, autoimmune neuropathy, motor dysfunction, and vasculitis. Across clinical trials of OPDIVO administered at doses 3 mg/kg and 10 mg/kg, additional clinically significant, immune-mediated adverse reactions were identified: hypophysitis, diabetic ketoacidosis, hypopituitarism, Guillain-Barré syndrome, and myasthenic syndrome. Based on the severity of adverse reaction, withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone- replacement therapy.

Embryofetal Toxicity

Based on its mechanism of action, OPDIVO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from OPDIVO, advise women to discontinue breastfeeding during treatment.

Serious Adverse Reactions

In Trial 1, serious adverse reactions occurred in 41% of patients receiving OPDIVO. Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase.
In Trial 3, serious adverse reactions occurred in 59% of patients receiving OPDIVO. The most frequent serious adverse drug reactions reported in ≥2% of patients were dyspnea, pneumonia, chronic obstructive pulmonary disease exacerbation, pneumonitis, hypercalcemia, pleural effusion, hemoptysis, and pain.

Common Adverse Reactions

The most common adverse reactions (≥20%) reported with OPDIVO in Trial 1 were rash (21%) and in Trial 3 were fatigue (50%), dyspnea (38%), musculoskeletal pain (36%), decreased appetite (35%), cough (32%), nausea (29%), and constipation (24%).