On February 29, 2016 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported financial results for the fourth quarter and full year ended December 31, 2015, which included a fourth quarter increase in royalty revenue of 136 percent from the prior year period and net income of $4.3 million, or $0.03 per share, compared to a net loss in the fourth quarter of 2014 of $5.3 million, or $0.04 per share (Press release, Halozyme, FEB 29, 2016, View Source [SID:1234509280]). For the full year, total revenue increased 79 percent to $135.1 million compared to $75.3 million in the prior year.

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"We closed 2015 with record progress across both pillars of our strategy and enter 2016 with strong momentum," said Dr. Helen Torley, president and chief executive officer. "In our oncology pillar, an investigational device exemption was submitted to the FDA earlier this month by our partner Ventana for the PEGPH20 companion diagnostic test. We remain on track to dose the first patient in March in our Phase 3 study in pancreatic cancer patients. We are also continuing to evaluate the dose of PEGPH20 in our lung and gastric cancer trials and are preparing for the initiation of the breast cancer trial with our clinical partner Eisai.

"At the same time, our ENHANZE platform continues to generate more value than any other time in company history. With royalty revenue growth in the fourth quarter, a newly signed licensing and collaboration agreement with Eli Lilly and four co-formulated products in the clinic, our ENHANZE platform remains a clear differentiator in any market environment."

Fourth Quarter 2015 Highlights and Subsequent Events include:

Submitting an investigational device exemption to the FDA for the companion diagnostic test developed with Ventana to prospectively identify patients with high levels of hyaluronan, or HA.

Remaining on track to dose first patient in HALO-301 | Pancreatic study in March 2016, a Phase 3 study to explore PEGPH20 with gemcitabine and ABRAXANE (nab-paclitaxel) in metastatic pancreatic cancer patients at approximately 200 sites in 20 countries located in North America, Europe, South America and Asia Pacific.

Closing enrollment in HALO-202 | Pancreatic study with 133 patients in Stage 2 (total 279 patients enrolled), the company remains blinded to the efficacy results and continues to project mature progression-free survival data and overall response rate data in the fourth quarter of 2016.

Continuing to explore the pan-tumor potential of PEGPH20, the company made progress towards identifying the maximum tolerated dose of PEGPH20 in its phase 1b/2 PRIMAL study of PEGPH20 plus docetaxel in lung cancer patients, and Phase 1b study of PEGPH20 plus KEYTRUDA (pembrolizumab) in lung and gastric cancer patients. In addition, Halozyme expects to initiate the study of PEGPH20 plus eribulin in HER2 negative breast cancer patients through a clinical collaboration with Eisai in the second quarter of 2016.

Signing the company’s sixth collaboration and licensing agreement for Halozyme’s proprietary ENHANZE technology platform with Eli Lilly for up to five targets, each with potential milestone payments of $160 million. The agreement resulted in a $25 million upfront license fee to Halozyme that was recorded in the fourth quarter.

Earlier this month, dosing the first subject in Pfizer’s Phase 1 clinical trial evaluating the safety, tolerability and pharmacokinetics of bococizumab, an investigational PCSK9 inhibitor developed by Pfizer, Inc. using Halozyme’s ENHANZE platform. The initiation of the clinical trial triggered a $1 million milestone payment to Halozyme under the collaboration and license agreement between Halozyme and Pfizer entered into in 2012.

In January, dosing the first subject in AbbVie’s Phase 1 clinical trial evaluating the safety and pharmacokinetics of adalimumab (HUMIRA) with Halozyme’s ENHANZE platform, resulting in a $5 million milestone payment under the collaboration and license agreement between Halozyme and AbbVie entered into in June of 2015.

In the fourth quarter, dosing the first subjects in Pfizer’s Phase 1 clinical trial of rivipansel and Janssen’s Phase 1b clinical trial of daratumumab with Halozyme’s ENHANZE platform.

Fourth Quarter and Full Year 2015 Financial Highlights

Revenue for the fourth quarter was $52.2 million, compared to $30.4 million for the fourth quarter of 2014, driven primarily by the upfront license fee from Eli Lilly and royalties from partner sales of Herceptin SC, MabThera SC and HyQvia. Revenue for the quarter included $9.5 million in royalties, $9.3 million in sales of bulk rHuPH20 for use in manufacturing collaboration products and $4.3 million in HYLENEX recombinant (hyaluronidase human injection) product sales. Revenue for the full year was $135.1 million compared to $75.3 million in the previous year.

Research and development expenses for the fourth quarter were $27.7 million, compared to $19.7 million for the fourth quarter of 2014. The planned increases were primarily due to expenses for preclinical and clinical support of PEGPH20.
Selling, general and administrative expenses for the fourth quarter were $10.6 million, compared to $8.4 million for the fourth quarter of 2014. The increase was primarily due to an increase in personnel expenses, including stock compensation, for the period.

Net income for the fourth quarter was $4.3 million, or $0.03 per share, compared to a net loss in the fourth quarter of 2014 of $5.3 million, or $0.04 per share. The net loss for the full year totaled $32.2 million, or $0.25 per share, compared to a net loss of $68.4 million, or $0.56 per share, for 2014.

Cash, cash equivalents and marketable securities were $108.3 million at Dec. 31, compared to $123.7 million at Sept. 30, 2015. Net cash burn during 2015 was approximately $27.3 million.

Financial Outlook for 2016
For the full year 2016, the company maintains its previously announced guidance of:

Net revenues to be in the range of $110 million to $125 million;

Operating expenses to be in the range of $240 million to $260 million;

Cash Flow to be in the range of $35 million to $55 million; and

Year-end cash balance of $140 million to $160 million.

– See more at: View Source#sthash.wZdqZ0fm.dpuf

On February 29, 2016 Juno Therapeutics, Inc. (NASDAQ:JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported business highlights and financial results for the fourth quarter and year ended December 31, 2015 (Press release, Juno, FEB 29, 2016, View Source;p=RssLanding&cat=news&id=2144320 [SID:1234509281]).

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"2015 was a year of significant progress for our clinical pipeline with encouraging data from our most advanced pipeline candidates, particularly in B cell malignancies. We are preparing for our first potential launch in r/r adult ALL as early as 2017, which if successful, creates the opportunity to change the current standard of care," said Hans Bishop, Juno’s President and Chief Executive Officer. "We also made significant advances in building our capabilities to support our goal of developing best-in-class CAR and TCR therapies. We look forward to a strong 2016 as we leverage these capabilities, our pipeline, and our people to create value for patients and shareholders."

2015 and Recent Corporate Highlights

CD19 Portfolio – Significant advances with Juno’s CD19-directed portfolio across B cell malignancies including relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL):

ALL – The Phase II ROCKET trial for JCAR015, a CD19-directed CAR T cell product candidate, continues to enroll adult r/r ALL patients in a potential U.S. registration trial that could lead to product approval as early as 2017. Data in 32 patients with pediatric r/r ALL with JCAR017 are encouraging, with a 91% complete remission (CR) rate, all of which are a complete molecular remission (CmR) as measured by flow cytometry, as presented at the 4th International Conference on Immunotherapy in Pediatric Oncology in September 2015. At the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in December 2015 (ASH 2015), investigators presented data for JCAR014 in adult r/r ALL showing that improved cell persistence, using the pre-conditioning regimen Juno plans to use going forward, led to deeper remissions and better duration of response, with 17/17 (100%) adult patients achieving a CR and a CmR.

NHL – Juno began enrollment of a multi-center Phase I trial for JCAR017 in r/r NHL and expects enrollment to continue through 2016. Investigators reported data at ASH (Free ASH Whitepaper) 2015 from the ongoing Phase I trial for JCAR014 in r/r NHL, and using the dose and pre-conditioning regimen Juno plans to study further, 7/11 patients (64%) of patients achieved a complete response, including 6/8 (75%) of patients with the diffuse large B cell (DLBCL) sub-type of NHL. No patient with a complete response had progressed (range of 2–9 months) as of the data cut-off date. Enrollment in this study continues, and Juno expects to have greater numbers of patients and longer duration of follow-up in 2016.

An IND for a combination trial of JCAR014 and MedImmune’s investigational programmed death ligand 1 (PD-L1) immune checkpoint inhibitor, durvalumab, cleared the U.S. Food and Drug Administration in late 2015, and Juno expects to enroll patients through 2016. Juno also expects to begin a Phase I trial for its CD19/4-1BB ligand armored CAR in 2016.

CLL – Investigators presented data at ASH (Free ASH Whitepaper) 2015 of JCAR014 in r/r CLL in patients previously treated with ibrutinib. All 7 patients treated with JCAR014 using the pre-conditioning regimen Juno plans to use going forward had a response, with 4/7 (57%) having a complete response. No patient achieving a response had progressed (range 2-14 months) as of the data cut-off date. Enrollment in this study continues, and Juno expects to have greater numbers of patients and longer duration of follow-up in 2016.
The safety profile across the CD19 portfolio remains consistent with what has been previously reported, with cytokine release syndrome and neurotoxicity the most common severe drug-related side effects. JCAR015, JCAR017, and JCAR014 are investigational product candidates and their safety and efficacy have not been established.

JCAR018 – This CD22-directed, fully human CAR T cell product candidate provides an opportunity to treat or prevent CD19-negative relapses. JCAR018 recently reached its first clinical milestone in a Phase I trial being run at the National Cancer Institute (NCI) in pediatric and young adult r/r ALL patients, which triggered a payment to Opus Bio in the first quarter of 2016 of 408,068 shares of Juno stock. Investigators presented interim data from this ongoing study at ASH (Free ASH Whitepaper) 2015, and Juno expects additional data to be presented from this trial later in 2016. In combination with CD19-directed CARs, CD22-directed CAR T treatment has the potential to meaningfully increase the percentage of ALL patients that experience long-term remissions.

Completed construction of the Juno manufacturing plant in Bothell, WA in 2015. Juno expects to begin supplying the vast majority of the clinical trial material for the ROCKET trial from this facility before the end of the first quarter of 2016 and bring production of other product candidates to this facility in 2016.

Juno began trials for solid tumor product candidates against four different targets in 2015 and early 2016 – JCAR024 (ROR-1-directed CAR T), JCAR020 (MUC-16-directed armored CAR T engineered to secrete IL-12), JCAR023 (L1-CAM-directed CAR T), and JTCR016 (WT-1- directed TCR). These trials explore treatment across a variety of solid organ tumor settings with data expected over the next 6-18 months.

Entered into a ten-year collaboration with Celgene to leverage T cell therapeutic strategies with an initial focus on CAR T and TCR therapies. Celgene gained the option to commercialize Juno programs outside North America and China and to co-promote certain programs globally. Juno has gained the option to co-develop, co-promote, and share profits with respect to select Celgene programs. In connection with the collaboration and stock purchase agreement, Juno received $1.0 billion.

Completed three acquisitions, which substantially increased Juno’s capabilities, including:

AbVitro, a leading next-generation single cell sequencing platform company that will augment Juno’s capabilities to create best-in-class engineered T cells against a broad array of cancer targets, including significantly improving the speed of generating TCR binders, while also enabling comprehensive profiling of functional immune repertoires with cancer tissues. Juno and Celgene have agreed in principle to enter an agreement to license Celgene a subset of the acquired technology and grant Celgene options to certain related potential product rights emanating from the acquired technology.

X-Body, Inc., an innovative discovery platform that interrogates the human antibody repertoire, rapidly selecting fully-human antibodies and single-chain variable fragments (scFv’s) with desired characteristics, even against difficult targets. Fully-human scFv’s have a lower risk of generating an immune response in the patient, which may allow Juno’s CAR T cell therapies to persist longer and generate a greater clinical benefit.

Stage Cell Therapeutics GmbH, a leading research-based company with transformative, fully reversible cell selection and activation capabilities as well as next-generation automation technologies for manufacturing. These capabilities and technology have the potential to help Juno make better therapies for patients and make them more broadly accessible with improved manufacturing capabilities.

Completed a number of licensing transactions to expand Juno’s research and development capabilities, including:

Fate Therapeutics: to identify and use small molecules with a goal of creating improved, next-generation CAR T and TCR products by modulating cell signaling pathways;

Editas: to use Editas’ genome editing technologies, including CRISPR/Cas9, in creating improved, next-generation CAR T and TCR products through gene editing; and

MedImmune: to support Juno’s trial combining JCAR014 and MedImmune’s anti-PD-L1 immune checkpoint inhibitor, durvalumab. This is the first trial to combine a CAR T cell therapy with a checkpoint inhibitor.

Reached a favorable settlement that resolved litigation with the University of Pennsylvania and Novartis Pharmaceuticals Corporation regarding Juno’s exclusive patent license from St. Jude Children’s Research Hospital. Settlement terms included an initial $12.3 million payment to Juno as well as potential future milestone and royalty payments to Juno from Novartis’ CD19-directed CAR T cell products using a 4-1BB co-stimulatory domain.

Built key capabilities and hired key talent, including the appointments of Robert Azelby as Executive Vice President, Chief Commercial Officer and Hyam I. Levitsky, M.D. as Executive Vice President, Research and Chief Scientific Officer. As part of Juno’s ongoing organizational growth, Mark Frohlich, M.D. will transition to the role of Executive Vice President of Portfolio Strategy and Robin Andrulevich has been promoted to Senior Vice President of People.

Fourth Quarter and 2015 Financial Results
Cash Position: Cash, cash equivalents, and marketable securities as of December 31, 2015 were $1.22 billion compared to $474 million as of December 31, 2014. In the third quarter of 2015, Juno sold 9,137,672 shares of its common stock and certain future stock purchase rights to Celgene for $93.00 per share resulting in proceeds of $850 million and received a cash payment of $150 million in connection with the collaboration agreement.

Cash Burn: Excluding cash inflows and outflows from business development activities and litigation, cash burn for 2015 was $147.8 million, consistent with guidance of $125.0 million to $150.0 million. Cash burn for 2015 was comprised of net cash used in operations of $119.6 million associated with the growth of Juno’s operations, including advancing Juno’s programs and headcount growth, and $28.2 million related to the build out of Juno’s manufacturing facility and purchase of general lab equipment. Cash burn for the fourth quarter of 2015 was $51.4 million and included cash used in operations of $46.6 million related to the growth of Juno’s operations, including headcount growth, and $4.8 million in capital expenditures.

Revenue: Revenue was $4.2 million for the fourth quarter of 2015 and $18.2 million for the year ended December 31, 2015. The fourth quarter included $3.8 million recognized in connection with the Celgene collaboration agreement.

R&D Expenses: Research and development expenses for the three and twelve months ended December 31, 2015, inclusive of non-cash expenses and computed in accordance with GAAP, were $75.6 million and $205.2 million, respectively, compared to $182.1 million and $204.5 million for the three and twelve months ended December 31, 2014, respectively.

Research and development expenses increased in 2015 compared to 2014 due to increased expenses associated with expanding Juno’s enrollment in clinical trials and overall investment in research and development capabilities, headcount growth, non-cash stock-based compensation expense, and advancing programs at Juno’s founding institutions.

Research and development expenses decreased in the fourth quarter of 2015 compared to the fourth quarter of 2014 due to lower expenses associated with the acquisition of technology.

The expense related to the success payment liability for the three and twelve months ended December 31, 2015 was $34.3 million and $51.6 million, respectively, compared to $83.5 million and $84.9 million for the same periods in 2014. The decrease in the expense related to the success payment liability in 2015 compared to 2014 is primarily due to the decline in Juno’s stock price as of December 31, 2015 compared to December 31, 2014. In December 2015, success payment obligations to Fred Hutchinson Cancer Research Center (FHCRC) were triggered in the amount of $75.0 million, less indirect cost offsets of $3.3 million, and to Memorial Sloan Kettering Cancer Center (MSK) of $10.0 million, less indirect cost offsets that will be determined at the time of payment to MSK in March 2016. Juno elected to make the payment to FHCRC in shares of Juno common stock, and thereby issued 1,601,085 shares of Juno common stock to FHCRC in December 2015. The success payment obligation to MSK is required to be paid, in cash or shares of Juno common stock at Juno’s election, on March 18, 2016.

Non-GAAP R&D Expenses: Non-GAAP research and development expenses for the three and twelve months ended December 31, 2015 were $41.1 million and $116.5 million, respectively. Non-GAAP research and development expenses include $3.6 million and $10.9 million of stock-based compensation expense for the three and twelve months ended December 31, 2015, respectively. Non-GAAP research and development expenses in 2015 exclude the following:

An expense of $34.3 million and $51.6 million for the three and twelve months ended December 31, 2015, respectively, associated with the change in estimated value and elapsed service period for Juno’s potential success payment liabilities to FHCRC and MSK, as well as the success payments achieved in 2015.

Upfront payments under the Editas and Fate Therapeutics license agreements of $30.8 million for the twelve months ended December 31, 2015.

Non-cash stock-based compensation expense of $1.4 million and $6.2 million for the three and twelve months ended December 31, 2015, respectively, related to a 2013 restricted stock award to a co-founding director that became a consultant upon his departure from Juno’s board of directors in 2014.

The change of $1.1 million in the fourth quarter of 2015 in the estimated fair value of the contingent consideration recorded in connection with the Stage and X-Body acquisitions.

G&A Expenses: General and administrative expenses on a GAAP basis for the three and twelve months ended December 31, 2015 were $16.0 million and $51.1 million, respectively, compared with $6.1 million and $19.5 million for the three and twelve months ended December 31, 2014, respectively. The increase of $9.9 million and $31.6 million for the three and twelve months ended December 31, 2015, respectively, was primarily due to increased personnel expenses, including non-cash stock-based compensation expense, costs associated with the Stage, X-Body, Celgene, Fate Therapeutics, Editas, and other business development transactions, an increase in patent and corporate legal fees, costs incurred to support expansion of the company, and costs associated with being a public company. General and administrative expenses include $5.4 million and $14.9 million of stock-based compensation expense for the three and twelve months ended December 31, 2015, respectively.

GAAP Net Loss Attributable to Common Stockholders: Net loss attributable to common stockholders for the three and twelve months ended December 31, 2015 was $85.2 million, or $0.89 per share, and $239.4 million, or $2.72 per share, respectively. This compares to $191.9 million, or $13.68 per share, and $310.9 million, or $36.82 per share, respectively, for the same periods in 2014.

Non-GAAP Net Loss Attributable to Common Stockholders: Non-GAAP net loss attributable to common stockholders for the three and twelve months ended December 31, 2015 was $50.7 million, or $0.53 per share, and $150.7 million, or $1.72 per share, respectively.

A reconciliation of GAAP net loss to non-GAAP net loss is presented below under "Non-GAAP Financial Measures."

2016 Financial Guidance
Juno expects 2016 cash burn, excluding cash inflows or outflows from business development activities and including the assumption that Celgene exercises its CD19 opt-in rights, to be between $220 million and $250 million.
Operating burn estimated to be between $170 million and $195 million.

Capital expenditures estimated to be between $40 million and $55 million, the vast majority of which are related to one-time infrastructure build-outs.

On February 29, 2016 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), an innovative company specializing in the development of orphan oncology therapeutics, reported that it has reached an agreement to acquire DNA Therapeutics, a privately-held, clinical-stage biopharmaceutical company, for its signal-interfering DNA (siDNA) repair technology, which is directed at overcoming cancer resistance mechanisms, and includes lead product candidate DT01 (Press release, Onxeo, FEB 29, 2016, View Source [SID:SID1234515571]). The acquisition, which is subject to customary closing conditions, is expected to close by the end of March 2016.

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The acquisition of DNA Therapeutics continues to demonstrate Onxeo’s commitment to developing novel orphan oncology drugs that position the Company at the forefront of scientific research for rare cancers with high, unmet medical needs, and have the potential to generate significant value for the Company and its stakeholders by opening other indications and markets.

Under the terms of the agreement, Onxeo is acquiring DNA Therapeutics for an upfront payment of €1.7 million in common shares at deal closing. Additional payment will come in the form of milestones including €1 million in cash or in ONXEO shares, at ONXEO’s sole discretion, upon successful initiation of a Phase II trial in a selected indication as well as royalty payments on future commercial sales, up to €25 million per indication developed and approved.

In conjunction with the transaction, in parallel with the contribution in kind, a large part of DNA Therapeutics’ historical shareholders have agreed to invest €1 million in cash in Onxeo shares, showing their full support to Onxeo to take over the development of the siDNA technology.

Interview of Judith Greciet: View Source,2292.html

The signal-interfering DNA (siDNA) innovation

Through DNA Therapeutics, Onxeo is acquiring a first-in-class clinical signal-interfering DNA (siDNA) molecule breaking the cycle of tumor DNA repair while sparing healthy cells. The siDNA technology offers a potential new treatment option for patients suffering from various types of cancer.

A first-in-human Phase 1/2a trial performed in metastatic melanoma demonstrated that siDNA molecules showed good tolerance and safety when administered intra-tumorally and subcutaneously around the tumors. Onxeo now plans to initate the development of this first-in-class product by the systemic route, and to assess their safety and tolerance in monotherapy and in combination with other DNA-damaging agents in various solid tumors. This clinical development will be implemented after first optimizing the manufacturing process, set to start as soon as the deal closes.

Judith Greciet, CEO of Onxeo, commented: "The acquisition of DNA Therapeutics and its siDNA technology represents a significant milestone for Onxeo. We are excited about this opportunity, which, based on its differentiated mechanism of action to fight cancer, will be significant in strengthening the level of innovation in our orphan oncology portfolio and instrumental in delivering value for our shareholders. The development of new agents specifically targeting DNA repair while sparing healthy tissues is imperative in the treatment of many solid tumors. Based on preclinical findings, we plan to evaluate the product in orphan oncology indications where a systemic application is suitable and for which there is significant unmet need, for example triple-negative breast cancer and platinum-resistant ovarian cancer".

Update on Validive further steps

Over the course of 2015, Onxeo has continued to advance the clinical development of Validive and notably its validation by the US and European regulatory agencies. Despite recognition from both agencies of Validive’s interest and value to patients, these discussions have confirmed that two Phase 3 clinical trials will be required for registration in the US, which makes the further clinical program significantly longer and more costly than expected. Therefore, the Company has decided it is in the best interest of its shareholders to move forward with this Phase 3 program only with the support of a partner. While actively seeking for such collaboration, Onxeo will continue to promote the scientific value of Validive through presentations at meetings.

"Validive remains a key asset in our orphan oncology pipeline. We have successfully developed the product to date and it is ready to enter Phase 3 as soon as we find the appropriate partner," commented Judith Greciet. "We are particularly excited about the acquisition of DNA Therapeutics and its first-in-class product-candidate which largely complements our core expertise and scientific ambitions. We believe it will be a tremendous addition to our pipeline, creating sound opportunity for short-to-long term milestones, adding value for our shareholders and bringing potentially new treatment options to patients with rare cancers."

About DNA repair

Biological responses to DNA damage and approaches to prevent the repair mechanisms allowing cancer cells to escape treatments have been identified as one of the most promising new avenues in cancer treatment. Most therapies against cancer induce DNA damage to tumor cells. DNA damage can also occur spontaneously in certain types of genetically unstable cancers. Yet cancer cells have the ability to recognize DNA damage and activate multiple DNA repair pathways or proteins to survive damages. These DNA repair processes contribute to cancer aggressiveness and resistance.

About the signal-interfering DNA (siDNA) technology

The siDNA technology developed by DNA Therapeutics, and acquired by Onxeo, breaks the cycle of cancer DNA repair activities by interfering at the core of DNA damage and interfering with multiple repair pathways, while sparing healthy cells. The technology, known as Dbait, was invented by Marie Dutreix, Research Director at The French National Centre for Scientific Research (CNRS), and Jian-Sheng Sun, Professor at The French National Museum of Natural History (Museum National d’Histoire Naturelle) in Paris, and further developed in Dr. Dutreix’s lab at Institut Curie. DNA Therapeutics was formed as a spin-out of the Institut Curie and three other French academic institutions.

The siDNA molecule is a short double-stranded DNA molecule that acts as a decoy, providing a false DNA break signal to attract DNA repair proteins which prevents the recruitment of repair enzymes to the site of actual DNA damage. Cancer cells do not have the ability to stop division in the face of DNA damage; they will continue dividing with the damaged DNA and therefore die. Healthy cells, on the other hand, will halt cell division until the compound is no longer present and damaged DNA can be repaired.

In a variety of preclinical animal models, the siDNA molecule demonstrated an increase in the efficacy of radiotherapy1, radiofrequency ablation2, and chemotherapy3, and has not lead to toxicity with repeated cycles of treatment, making it a promising candidate for both monotherapy and combination therapy. A first-in-human Phase 1/2a trial, "DNA Repair Inhibitor & Irradiation on Melanoma" (DRIIM; NCT01469455), in patients with metastatic melanoma demonstrated the safety of local administration of the product. Additionally, no maximum-tolerated dose (MTD) was identified and the product showed excellent tumor response correlated with systemic exposure.

On February 27,2016 Celgene Corporation (NASDAQ:CELG) reported that two interim analyses of exploratory quality of life (QoL) endpoints in the ongoing phase III ABOUND.sqm clinical study investigating ABRAXANE (paclitaxel protein-bound particles for injectable suspension)(albumin-bound) in patients with advanced, squamous non-small cell lung cancer (NSCLC) were presented at the 2016 ASCO (Free ASCO Whitepaper) Quality Care Symposium (Press release, Celgene, FEB 27, 2016, View Source [SID:1234509247]).

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In the ABOUND.sqm study, patients received four 21-day cycles of ABRAXANE (100 mg/m2 on days 1, 8 and 15) plus carboplatin (AUC6 on day 1) and those with a response or stable disease could be randomized to receive either ABRAXANE (100 mg/m2 on days 1, 8) plus best supportive care or best supportive care alone in 21-day cycles until disease progression.

The analyses included 159 patients from the study who were evaluable for radiological response and QoL. In the two analyses 99% of patients had an ECOG performance status of 0-1 and pre-defined QoL measures including the LCSS (Global Score, Average Total Score, 3-Item Index, Average Symptom Burden Index and Lung Cancer Symptoms) and EuroQol EQ-5D-5L assessment were taken on day one of each cycle during the initial treatment phase.

The first analysis evaluated the therapeutic impact of chemotherapy on patient symptoms and activities. For all patients in the analysis, quality of life as measured by the LCSS and EuroQoL (EQ-5D-5L) was generally either maintained or improved throughout the entire treatment course.

The second analysis assessed the impact of radiological response on Quality of Life. In this analysis, 93/159 patients had an unconfirmed radiological response and 66/159 did not. Responders had a greater improvement in lung cancer symptom score, as measured by the LCSS and EQ-5D-5L scores.

Importantly, among patients who reported problems with mobility, self care, usual activities of living, pain/discomfort, or anxiety/depression prior to treatment, 38 – 47% reported complete resolution of these problems at least once during treatment. This was more pronounced in patients who achieved a radiological response, with complete resolution at least once reported in 42 – 59% of patients.

"Inclusion of quality of life measures is particularly important when so few prospective trials in advanced non-small cell lung cancer currently include such analyses," said Dr. Corey Langer of the University of Pennsylvania and lead investigator of one of the analyses. "These data demonstrate a correlation between radiologic response and patient reported quality of life."

Indication

ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

Important Safety Information

WARNING – NEUTROPENIA

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE

Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS

Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS

Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 47% of patients with non-small cell lung cancer (NSCLC)

Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15

Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3

In the case of severe neutropenia ( < 500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with NSCLC

Resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle

Nervous System

Sensory neuropathy is dose- and schedule-dependent

The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification

If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to ≤ Grade 1 followed by a dose reduction for all subsequent courses of ABRAXANE

Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug

Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution

Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression

For NSCLC, the starting dose should be reduced for patients with moderate or severe hepatic impairment

Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood

Use in Pregnancy: Pregnancy Category D

ABRAXANE can cause fetal harm when administered to a pregnant woman

If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus

Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE

Use in Men

Men should be advised not to father a child while receiving ABRAXANE

ADVERSE REACTIONS

Non-Small Cell Lung Cancer (NSCLC) Study

The most common adverse reactions (≥20%) of ABRAXANE in combination with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue

The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC are anemia (4%) and pneumonia (3%)

The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%)

The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)

The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%)

The following common (≥10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin-treated and paclitaxel injection plus carboplatin-treated patients: alopecia (56%), nausea (27%), fatigue (25%), decreased appetite (17%), asthenia (16%), constipation (16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash (10%); incidence rates are for the ABRAXANE plus carboplatin treatment group

Adverse reactions with a difference of ≥2%, Grade 3 or higher, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%), respectively

Adverse reactions with a difference of ≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%, 2%), arthralgia (13%, 25%), and myalgia (10%, 19%), respectively

Neutropenia (all grades) was reported in 85% of patients who received ABRAXANE and carboplatin vs 83% of patients who received paclitaxel injection and carboplatin

Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied

There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs

There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration

DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4

USE IN SPECIFIC POPULATIONS

Nursing Mothers

It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated

Geriatric

Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC

Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)

DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN

Reduce starting dose in NSCLC patients with moderate to severe hepatic impairment

Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicity

Monitor patients closely

Please see full Prescribing Information, including Boxed WARNING.

On February 26, 2016 Portola Pharmaceuticals (Nasdaq:PTLA) reported a corporate update and its financial results for the fourth quarter and year ended December 31, 2015 (Press release, Portola Pharmaceuticals, FEB 26, 2016, View Source;p=RssLanding&cat=news&id=2143706 [SID:1234509238]).

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"During the fourth quarter of 2015, we executed on several milestones that we expect will make 2016 a year of unprecedented progress. We plan to commercially launch andexanet alfa and report pivotal Phase 3 results from our APEX study that, if positive, will support the global approval of betrixaban," said Bill Lis, chief executive officer of Portola. "Both have the potential to benefit the patients and transform the field in the multibillion dollar thrombosis market. Additionally, our R&D pipeline continues to progress with our ongoing Phase 1/2 study with cerdulatinib, our oral, dual syk/JAK inhibitor in refractory/relapsed hematologic cancer patients."

Recent Achievements, Upcoming Events and Milestones

Betrixaban – an FDA-designated Fast Track oral Factor Xa inhibitor anticoagulant in development for the prevention of venous thromboembolism (VTE) in acute medically ill patients.

Plan to report topline results from the 7,514-patient pivotal Phase 3 APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban) Study in early April.

Plan to submit a New Drug Application to the FDA in the second half of 2016, subject to positive APEX data.

Andexanet alfa – an FDA-designated Breakthrough Therapy Factor Xa inhibitor antidote in development for reversal of anticoagulation in patients treated with a Factor Xa inhibitor and who are admitted to the hospital with uncontrolled bleeding or need urgent surgery.

The FDA accepted the Biologics License Application (BLA) for filing February 16, 2016. The BLA was granted a priority review under an Accelerated Approval pathway, and assigned a PDUFA date of August 17, 2016. We plan to launch andexanet alfa commercially in the U.S. in the second half of 2016, subject to FDA approval.

The full data set from the ANNEXA-R study with rivaroxaban was presented in a Late-Breaking Clinical Trial Session at the American Heart Association’s Scientific Sessions 2015 and simultaneously published in the New England Journal of Medicine.

Licensed development and commercial rights in Japan to Bristol-Myers Squibb Company and Pfizer Inc. Separately, entered into a clinical collaboration agreement with Bayer HealthCare to include its Factor Xa inhibitor rivaroxaban in the development program in Japan.

Continue to enroll patients in ANNEXA-4, a Phase 4 confirmatory study of patients receiving apixaban, rivaroxaban, edoxaban or enoxaparin who present to the hospital with an acute major bleed.

Plan to present data from the Phase 2 proof-of-concept andexanet study with betrixaban in healthy volunteers at a medical conference in 2016 The study was designed to evaluate safety and define the dose of andexanet required to reverse the anticoagulant effect of betrixaban.

Plan to complete FDA pre-approval inspection of the initial (Generation 1 2,500 liter scale at CMC Biologics). Generation 1 validation batch runs at the 6 x 2,000 liter scale are ongoing.

Completed two Generation 2 engineering batches manufactured by Lonza at the 10,000 liter scale, with target yields achieved. Expect commercial validation batches to begin in the second half of 2016.

Cerdulatinib – an oral, dual Syk/JAK kinase inhibitor in development to treat resistant or relapsed hematologic cancer patients.

Presented three abstracts at the 2015 ASH (Free ASH Whitepaper) Annual Meeting on cerdulatinib’s preclinical activity in chronic lymphocytic leukemia; clinical and pharmacodynamic results of a Phase 1/2 study with relapsed/refractory B cell malignancies; and pharmacokinetic modeling of cerdulatinib plasma concentrations in patients with relapsed/refractory B cell malignancies.

Continue to dose-escalate for clinical activity and tolerability in the ongoing Phase 1/2 study in patients with relapsed/refractory B-cell malignancies. Plan to initiate enrollment in expansion cohorts this year.

Corporate

Raised $162.7 million in net proceeds from an underwritten public offering of common stock in December 2015.

Fourth Quarter and Year-End Financial Results
Collaboration revenue earned under Portola’s collaborations with Bristol-Myers Squibb Company and Pfizer, Bayer Pharma and Janssen Pharmaceuticals, Daiichi Sankyo and Lee’s Pharmaceutical was $4.4 million for the fourth quarter of 2015 compared with $2.4 million for the fourth quarter of 2014. Collaboration revenue for the year ended December 31, 2015, was $12.1 million compared with $9.6 million for the year ended December 31, 2014.

Total operating expenses for the fourth quarter of 2015 were $70.7 million compared with $41.7 million for the same period in 2014. Total operating expenses for the fourth quarter of 2015 included $6.8 million in stock-based compensation expense compared with $2.5 million for the same period in 2014. Total operating expenses for the year ended December 31, 2015, were $239.2 million compared with $147.2 million for 2014. Total operating expenses for the full year ended December 31, 2015, included $22.9 million in stock-based compensation expense compared with $9.3 million for 2014. Research and development expenses were $200.4 million for the year ended December 31, 2015, compared with $123.6 million for 2014, as the Company continued to support its manufacturing scale-up of andexanet alfa in preparation for the BLA submission and commercial launch and work on its larger-scale Generation 2 manufacturing process at Lonza, its Phase 3 and Phase 4 ANNEXA studies of andexanet alfa, completing enrollment in the Phase 3 APEX Study of betrixaban, and its Phase 1/2a clinical study of cerdulatinib. Selling, general and administrative expenses for the fourth quarter of 2015 were $10.9 million compared with $7.0 million for the same period in 2014. Selling, general and administrative expenses for the year ended December 31, 2015, were $38.9 million compared with $23.6 million for 2014, as the Company increased headcount to support its growth and increased pre-commercial launch activities, including hiring key regional sales directors and national account managers and further developing medical affairs.

For the fourth quarter of 2015, Portola reported a net loss of $66.1 million, or $1.23 net loss per share, compared with a net loss of $39.3 million, or $0.82 net loss per share, for the same period in 2014. Net loss for the year ended December 31, 2015, was $226.5 million, or $4.36 net loss per share, compared with a net loss of $137.1 million, or $3.19 net loss per share, for the same period in 2014.

Cash, cash equivalents and investments at December 31, 2015, totaled $460.2 million compared with cash, cash equivalents and investments of $392.3 million as of December 31, 2014.