8-K – Current report

On February 28, 2017 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported that it outperformed its financial guidance by ending 2016 with pro forma operating income of $25.8 million and $665.2 million in cash, cash equivalents and short-term investments (Press release, Ionis Pharmaceuticals, FEB 28, 2017, View Source [SID1234517888]). The Company also reported a GAAP loss from operations of $46.3 million.

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"2016 was a year of significant accomplishments for Ionis, culminating in the U.S. approval of SPINRAZA, in record time and with a very broad label. The approval of SPINRAZA is a testament to the efficacy, safety and tolerability that SPINRAZA demonstrated in multiple clinical studies in multiple SMA patient populations. We are pleased with Biogen’s early launch efforts in the U.S. and their actions directed to making SPINRAZA available to patients around the world as soon as possible," said B. Lynne Parshall, chief operating officer of Ionis Pharmaceuticals.

"In 2016, we reported positive clinical data from 11 studies with six drugs. We also continued to advance over 36 drugs in development, including our Phase 3 drugs, volanesorsen and IONIS-TTRRx, which will complete pivotal trials shortly. We also added five new drugs to our pipeline, including our first Generation 2.5 LICA drug and our first oral locally acting drug for gastrointestinal autoimmune diseases.

"In the first week of 2017, we and our subsidiary, Akcea, initiated a collaboration with Novartis to develop and co-commercialize AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx for patients with cardiovascular disease. Our partner for our Factor XI program, Bayer, is advancing IONIS-FXIRx and is expanding the program by initiating development of the LICA follow-on, IONIS-FXI-LRx. In addition, our broad strategic collaborations with Biogen and AstraZeneca continue to be productive. We believe our constellation of partnerships demonstrate the potential of our antisense drugs to address a wide variety of diseases with both large and small patient populations.

"In 2017, we expect to be breakeven or profitable at the operating line on a pro forma basis, driven in part by revenue from SPINRAZA. Biogen anticipates EU approval mid-year and has filed for regulatory authorization in Japan, Canada and Australia, and is planning to file additional applications in other countries this year. Approval in additional markets could broaden access to SPINRAZA and further bolster our revenues. We and Akcea expect to report Phase 3 data in March from the APPROACH study of volanesorsen in patients with familial chylomicronemia syndrome. Together with Akcea, we are preparing the regulatory submissions and plan to file for marketing authorization in the U.S., EU and Canada this year, provided the Phase 3 data are positive. Akcea has also made progress in preparing to launch volanesorsen. In the second quarter, we plan to report Phase 3 data from the NEURO-TTR study with IONIS-TTRRx in patients with familial amyloid polyneuropathy. We and our partner, GSK, are preparing to file an NDA before year end if the Phase 3 data are positive. While progress in these late-stage programs represents key visible catalysts for the year, we also plan to provide updates from our large and diverse pipeline throughout the year.

"We believe we have the key elements in place to achieve sustained, long-term financial growth. We have multiple drivers of revenue; a partnership strategy that leverages partner resources; a mature, broad and rapidly advancing clinical pipeline; and an innovative, more efficient drug discovery platform that enables us to continue developing new drugs with the potential for significant commercial opportunity in both rare and more prevalent diseases. We are now closer to achieving our goal of becoming a profitable, multi-product company delivering innovative medicines to patients with serious diseases," concluded Ms. Parshall.

Ionis’ 2017 goals and a list of corporate and drug development highlights can be found at the end of this press release prior to the financial tables.

Financial Results

"2016 was marked by continued progress, highlighted by the approval of SPINRAZA. We earned substantial license fees and milestone payments from our many achievements, which led us to significantly improve upon our revenue, pro forma net operating loss and cash guidance for 2016. In 2016, we generated $347 million of revenue, an increase of 45 percent compared to our guidance of $240 million. Importantly, we were able to achieve all of our 2016 accomplishments with only a nominal increase in our expenses over 2015. We ended 2016 with a GAAP loss from operations of $46 million, which included $72 million in non-cash compensation expense related to equity awards resulting in pro forma operating income of $26 million. In addition, we reported GAAP and pro forma net income for the third and fourth quarters. During the year, we received more than $190 million from our partners and ended the year with $665 million in cash, exceeding our year-end cash guidance by $65 million. This cash balance does not include more than $100 million that we earned in 2016 and received payment for in 2017," said Elizabeth L. Hougen, chief financial officer of Ionis Pharmaceuticals.

"We are pleased to add commercial revenue from SPINRAZA to our already significant revenue from partnerships. Over the past five years, we have consistently increased our revenue, reflecting the successes of our partnered programs and drugs. This R&D revenue provides a base of revenue that funds most of our pro forma operating expenses. While in any year the specific sources of our R&D revenue change, the consistent growth in revenue we have achieved over the last five years supports the sustainability of this component of our operating model. In 2017, we expect to continue to have a strong R&D revenue base that funds most of our pro forma operating expenses. To that revenue base, we are adding commercial revenue from SPINRAZA royalties. This revenue is nearly all profit to us, in other words we have only a nominal amount of corresponding expense associated with it. For 2017, we expect our operating expenses to be essentially flat compared to 2016; however, the composition of our expenses will change to reflect the evolution of our business. We plan to continue to increase our commercial spending for volanesorsen as our subsidiary, Akcea, prepares to launch volanesorsen globally in 2018. These increases will be offset by a decrease in our R&D expenses, reflecting the fact that our current Phase 3 programs are coming to a close. Because of the efficiency of our technology, we can advance our earlier stage drugs and add new drugs to our pipeline while still decreasing our research and development expenses. The combination of a solid base of R&D revenue, SPINRAZA commercial revenue and prudent spending, support our projection that we will be breakeven or profitable at the operating line on a pro forma basis for 2017. As we have more visibility on SPINRAZA sales, we will provide more detailed guidance. Already in 2017, we have generated more than $250 million in cash from our partnered programs. As such, we are projecting a year-end cash balance of over $825 million," concluded Ms. Hougen.

All pro forma amounts referred to in this press release exclude non-cash compensation expense related to equity awards. Please refer to the reconciliation of GAAP to pro forma measures, which is provided later in this release.

Revenue

Ionis’ revenue for the three and twelve months ended December 31, 2016 was $160.3 million and $346.6 million, compared to $51.6 million and $283.7 million for the same periods in 2015. Ionis’ revenue in 2016 consisted of the following:

·
$170 million from Biogen for FDA approval, licensing and advancing the Phase 3 program for SPINRAZA;
·
$53 million from AstraZeneca for advancing and licensing IONIS-KRAS-2.5Rx and selecting IONIS-AZ4-2.5-LRx to move into development;
·
$15 million from Janssen for licensing IONIS-JBI1-2.5Rx and validating an undisclosed target to treat patients with a gastrointestinal autoimmune disease;
·
$15 million from Kastle Therapeutics for acquiring Kynamro;
·
$8 million from Biogen for advancing IONIS-SOD1Rx, IONIS-BIIB4Rx and IONIS-BIIB6Rx;
·
$61 million from the amortization of upfront fees; and
·
$25 million primarily from its partners for the manufacturing services Ionis performed.

In comparison, Ionis’ revenue in 2015 included $115.7 million in milestone payments from partnered programs, $91.2 million in connection with Bayer’s exclusive license of IONIS-FXIRx, $56.2 million from the amortization of upfront fees and $20.6 million primarily from the manufacturing services Ionis performed for its partners.

Ionis’ revenue fluctuates based on the nature and timing of payments under agreements with its partners and consists primarily of revenue from the amortization of upfront fees, milestone payments and license fees.

Operating Expenses
Ionis’ operating expenses for the three and twelve months ended December 31, 2016 on a GAAP basis were $119.2 million and $392.9 million, respectively, and on a pro forma basis were $104.0 million and $320.8 million, respectively. This is compared to GAAP operating expenses of $114.5 million and $359.5 million and pro forma operating expenses of $97.1 million and $300.2 million for the same periods in 2015. The increase in operating expenses was primarily due to Phase 3 programs for SPINRAZA, IONIS-TTRRx and volanesorsen that Ionis conducted in 2016. The Company completed target enrollment in four of the Phase 3 studies at the end of 2015, and as a result, these studies were in their most expensive stage during 2016. In addition, Akcea continued to build a global organization and prepare for the launch of volanesorsen. In addition, Ionis’ operating expenses for 2016 on a GAAP basis increased due to an increase in non-cash compensation expense related to equity awards that resulted from an increase in the exercise price of the stock options the Company has granted over the past several years.

Loss on Retirement of Debt
In December 2016, Ionis refinanced a majority of its 2¾% convertible senior notes due 2019 (2¾% Notes). In the refinancing, Ionis reduced the interest rate to 1% by issuing an additional $185.5 million of its 1% convertible senior notes due 2021 (1% Notes). Ionis also significantly reduced the potential dilution from its convertible notes and extended the maturity to November 2021. As a result of the early repurchase of the 2¾% Notes, Ionis recognized a $4.0 million non-cash loss.

Income Tax Expense
Ionis recognized income tax expense of $2.9 million for the year ended December 31, 2016 compared to $0.4 million in 2015. Ionis’ tax expense increased in 2016 compared to 2015 primarily due to an increase in taxable income resulting from Ionis’ strong financial performance in 2016.

Net Income (Loss)
Ionis reported net income of $25.9 million and a net loss of $86.6 million for the three and twelve months ended December 31, 2016 on a GAAP basis, respectively, compared to a net loss of $71.4 million and $88.3 million for the same periods in 2015. Ionis recorded pro forma net income of $41.0 million for the three months ended December 31, 2016 compared to a pro forma net loss of $54.0 million for the same period in 2015. For the twelve months ended December 31, 2016, the Company had a pro forma net loss of $14.4 million compared to a pro forma net loss of $29.0 million in 2015. Basic and diluted net income per share for the three months ended December 31, 2016 on a GAAP basis was $0.21. Basic and diluted net loss per share for the twelve months ended December 31, 2016 was $0.72. This is compared to a basic and diluted net loss of $0.59 and $0.74 per share for the three and twelve months ended December 31, 2015, respectively.

Balance Sheet
As of December 31, 2016, Ionis had cash, cash equivalents and short-term investments of $665.2 million compared to $779.2 million at December 31, 2015. Ionis’ cash balance decreased in 2016 primarily due to spending to support the Company’s ongoing Phase 3 programs. Ionis’ cash balance at the end of 2016 did not include $107 million the Company earned in the fourth quarter of 2016 and received in 2017. Since the end of 2016, Ionis has generated more than $250 million primarily from its Novartis and Bayer partnerships. Ionis’ working capital was $664.1 million at December 31, 2016 compared to $688.1 million at December 31, 2015.

Halozyme Reports Fourth Quarter And Full Year 2016 Financial Results

On February 28, 2017 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported financial results and recent highlights for the fourth quarter and full year ended December 31, 2016 (Press release, Halozyme, FEB 28, 2017, View Source [SID1234517886]).

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"We exited 2016 in a strong position through the benefit of our differentiated business model and having made substantial progress across both of our value-creating pillars," said Dr. Helen Torley, president and chief executive officer. "The positive Phase 2 data we reported last month affirms our conviction in PEGPH20, our lead investigational oncology drug, and supports our ongoing Phase 3 study in pancreas cancer patients. We have made strong progress initiating global sites in the Phase 3 study and see momentum building in the number of patients we are screening.

"Our ENHANZE platform remains an important value driver as royalty revenue demonstrated yet another quarter of robust growth, and exceeded $50 million for the year. With positive data presented by Genentech and Janssen at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting for their ENHANZE-partnered programs and a recent BLA filing in the U.S. by Genentech, we remain very encouraged by the royalty growth potential from current and new products over the long term."

Fourth Quarter 2016 and Recent Highlights include:

Reporting a statistically significant improvement in the primary endpoint of progression-free survival (PFS) of all evaluable patients, and in the secondary endpoint of PFS in patients with high levels of hyaluronan (HA), as of a December 2016 data cut in the Phase 2 randomized HALO-202 study of PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine in advanced pancreas cancer patients. The primary safety endpoint to evaluate and demonstrate a reduction in the rate of thromboembolic events in the PEGPH20 arm was also achieved.

In the population that closely mirrors the HALO-301 Phase 3 study, a 91 percent improvement was achieved in median PFS for HA-High patients in the PEGPH20 arm, 8.6 months compared to 4.5 months in the control arm. A 50 percent improvement was also reported in median overall survival (OS) for HA-High patients in the PEGPH20 arm, 11.7 months compared to 7.8 months in the control arm.

Screening patients at nearly 200 global sites and receiving approval in all 22 participating countries for HALO-301, the company’s Phase 3 study of pancreas cancer patients.

Entering the dose expansion phase of the ongoing Phase 1b clinical study evaluating PEGPH20 in combination with KEYTRUDA (pembrolizumab) in relapsed non-small cell lung and gastric cancer patients. The company expects to enroll approximately 50 patients with high levels of HA at 30 U.S. sites.

Announcing a broad clinical collaboration agreement with Genentech to evaluate PEGPH20 and TECENTRIQ (atezolizumab) in up to 8 tumor types. Halozyme plans to initiate a Phase 1b trial to evaluate the combination in gallbladder cancer and cholangiocarcinoma, and Roche plans to initiate multiple Phase 1b/2 trials within their novel immunotherapy MORPHEUS clinical trial platform to evaluate the combination in pancreas and gastric cancers in the second half of 2017.

Presenting supportive clinical data by ENHANZE partners at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in November. Genentech presented data from the SABRINA Phase 3 study indicating comparable response rates and time-to-event data for subcutaneous rituximab compared to IV administration. The data presentation followed acceptance by the Food and Drug Administration (FDA) of a Biologics License Application for a subcutaneous formulation of rituximab using Halozyme’s ENHANZE technology. Roche has indicated it is seeking approval in chronic lymphocytic leukemia and non-Hodgkin’s lymphoma, with an action date in June.

In addition, Janssen presented data indicating its subcutaneous formulation of daratumumab on the ENHANZE platform was well tolerated and had an efficacy and pharmacokinetic profile consistent with the IV formulation, demonstrating the feasibility of a 30-minute, 90 mL dose and supporting further study in a Phase 3 clinical trial.
Fourth Quarter and Full Year 2016 Financial Highlights

Revenue for the fourth quarter was $39 million compared to $52.2 million for the fourth quarter of 2015. The year-over-year decrease was driven by $25 million received upon signing the Lilly collaboration agreement in 2015, offset by increases in royalties from partner sales of Herceptin SC, MabThera SC and HYQVIA, API sales to partners, and manufacturing and clinical supply reimbursements from ENHANZE partners. Revenue for the fourth quarter included $14.3 million in royalties, an increase of 50 percent from the prior-year period, $9 million in sales of bulk rHuPH20 primarily for use in manufacturing collaboration products and $4.4 million in HYLENEX recombinant (hyaluronidase human injection) product sales.

Revenue for 2016 totaled $146.7 million, an increase of 9 percent from 2015, including royalty revenue of $51 million, an increase of 65 percent from 2015.

Research and development expenses for the fourth quarter were $41.3 million, compared to $27.7 million for the fourth quarter of 2015. The planned increases were primarily due to a ramp in spending associated with the HALO-301 study, personnel expenses, and manufacturing and clinical supply expenses that are reimbursed by ENHANZE partners.

Selling, general and administrative expenses for the fourth quarter were $12.2 million, compared to $10.6 million for the fourth quarter of 2015. The increase was primarily due to personnel expenses, including stock compensation, for the period.

Operating expenses for 2016 totaled $229.9 million, an increase of 41 percent from 2015.

Net loss for the fourth quarter was $27.4 million, or $0.21 per share, compared to net income in the fourth quarter of 2015 of $4.3 million, or $0.03 per share. Net loss for 2016 totaled $103 million, or $0.81 per share.

Cash, cash equivalents and marketable securities were $205 million at December 31, 2016, compared to $221.1 million at September 30, 2016.
Financial Outlook for 2017

For 2017, the company reiterated and updated the cash portions of its financial guidance, now expecting:

Net revenue of $115 million to $130 million, excluding any new ENHANZE collaboration agreements;
Operating expenses of $240 million to $250 million;
Operating cash burn of $75 million to $85 million; and
Year-end cash balance of $110 million to $125 million, an increase from its prior range of $100 million to $110 million.
– See more at: View Source#sthash.gr8dP2Vt.dpuf

Actinium Announces Expansion of Intellectual Property Portfolio with Notice of Allowance for U.S. Patent Related to Actimab-A, Actimab-M and the Company’s Technology Platform

On February 28, 2017 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical Company developing innovative targeted payload immunotherapeutics for the treatment of advanced cancers, reported that the Company received a notice of allowance from the United States Patent and Trademark Office (USPTO) for a patent claiming the methods for generating a radioimmunoconjugate comprised of actinium-225, an alpha emitting radioisotope, conjugated to monoclonal antibodies (Press release, Actinium Pharmaceuticals, FEB 28, 2017, View Source [SID1234517883]).

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Actinium-225 is the radioisotope used in Actinium’s Actimab-A, a drug candidate in a Phase 2 clinical trial for patients newly diagnosed with acute myeloid leukemia (AML) who are over the age of 60; Actimab-M, a drug candidate in a Phase 1 trial for patients with relapsed or refractory multiple myeloma (MM); and the Company’s alpha particle immunotherapy technology platform. Actinium currently has 61 issued and pending patents that are owned or licensed relating to isotope production methods, drug preparation methods and the Company’s platform technology. This patent is expected to expire in July of 2030.

Sandesh Seth, Actinium’s Executive Chairman said, "Actinium-225 is an excellent isotope for medical applications given its half-life, potency, safety profile and relatively ease of handling. As a result, it is an important aspect of Actinium’s Actimab-A and Actimab-M programs and alpha particle immunotherapy technology (APIT) platform. We welcome this addition to our intellectual property portfolio, which now consists of more than 60 patents. We will continue to invest in our intellectual property portfolio to further enhance our position in the use of alpha particles to enhance outcomes for patients."

The claims of this patent are for a method for producing actinium-225 radioconjugates, the method comprising the steps of: a) conjugating a chelating agents to a biological molecule in a conjugations reaction mixture to generate a conjugated biological molecule, b) purifying the reaction mixture so as to remove unconjugated chelating agents, and c) chelating one or more actinium-225 radionuclides with the conjugated biological molecule in a chelation reaction mixture to generate an actinium-225 radioconjugate.

Kite Reports Fourth Quarter and Full Year 2016 Financial Results

On February 28, 2017 Kite Pharma, Inc. (Nasdaq:KITE) reported a corporate update and fourth quarter and full-year 2016 financial results for the period ended December 31, 2016 (Press release, Kite Pharma, FEB 28, 2017, View Source [SID1234517879]).

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In a separate announcement today, Kite issued positive topline results from the primary analysis of the ZUMA-1 study of axicabtagene ciloleucel in patients with aggressive non-Hodgkin lymphoma (NHL). Kite continues to expect completion of its rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for axicabtagene ciloleucel (KTE-C19) for the treatment of aggressive NHL by the end of the first quarter 2017, with potential approval and commercial launch in 2017.

"The accomplishments, leadership additions to the company, and performance of Kite during 2016 put us in a position of strength as we prepare to potentially deliver the first CAR-T therapy for aggressive NHL to patients later this year," said Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer. "Beyond axicabtagene ciloleucel, we have taken important steps to expand Kite’s global footprint and pipeline of cell therapy candidates. Through our recently announced strategic collaborations with Fosun Pharma and Daiichi Sankyo, our plans for submission and potential launch in Europe, and ongoing clinical studies of axicabtagene ciloleucel, we look ahead to an increasingly strong future for Kite."

Fourth Quarter and Full Year 2016 Financial Results

Revenues were $4.9 million for the fourth quarter of 2016 and $22.2 million for the full year of 2016.
Research and development expenses were $58.9 million for the fourth quarter of 2016, which includes $8.9 million of non-cash stock-based compensation expense. For the full year of 2016, research and development expenses were $197.9 million, which includes $34.7 million of non-cash stock-based compensation expense.
General and administrative expenses were $31.8 million for the fourth quarter of 2016, which includes $10.8 million of non-cash stock-based compensation expense. For the full year of 2016, general and administrative expenses were $97.4 million, which includes $38.8 million of non-cash stock-based compensation expense.
Net loss was $84.9 million, or $1.70 per share, for the fourth quarter of 2016. For the full year of 2016, net loss was $267.1 million, or $5.46 per share.
Non-GAAP net loss for the fourth quarter of 2016 was $65.2 million, or $1.31 per share, excluding non-cash stock-based compensation expense of $19.7 million. For the full year of 2016, non-GAAP net loss was $193.5 million, or $3.95 per share, excluding non-cash stock-based compensation expense of $73.6 million.
As of December 31, 2016, Kite had $414.4 million in cash, cash equivalents, and marketable securities. In January 2017, Kite received a $50 million upfront payment from Daiichi Sankyo related to the recently announced strategic collaboration in Japan.
2017 Financial Guidance

Kite expects full year 2017 net cash burn to be between $325 million and $340 million, which includes approximately $30 million in capital expenditures but excludes cash inflows or cash outflows from business development activities, if any, and excludes planned upfront payments totaling $90 million from recently announced strategic collaborations in Asia. Estimated full year 2017 cash burn is driven primarily by a projected GAAP net loss of between $450 million and $465 million. The 2017 projected net loss includes non-cash stock-based compensation expenses of approximately $135 million.
Kite expects full year 2017 revenue to be between $40 million and $50 million, which assumes no product revenue, and full year 2017 GAAP operating expenses to be between $490 million and $515 million.
As previously announced, Kite expects to have sufficient cash resources to fund its current operations, including planned clinical development programs, through the first half of 2018. This projection excludes cash inflows or cash outflows from future business development activity, if any.
2016 Highlights

Axicabtagene Ciloleucel/KTE-C19 Progress

Presented positive interim results from the ZUMA-1 Phase 2 study of axicabtagene ciloleucel in aggressive NHL in a late-breaker oral presentation at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.
Reported a Phase 1 update from the ZUMA-3 and ZUMA-4 trials of KTE-C19 in adult and pediatric relapsed/refractory acute lymphoblastic leukemia at the 2016 ASH (Free ASH Whitepaper) annual meeting.
Initiated ZUMA-6, a Phase 1b/2 study of axicabtagene ciloleucel in combination with the checkpoint inhibitor atezolizumab in patients with chemorefractory diffuse large B-cell lymphoma (DLBCL) in collaboration with Genentech.
Presented results from SCHOLAR-1, the first patient-level pooled analysis of outcomes in chemorefractory DLBCL, providing an important historical benchmark for studies of the disease.
Regulatory Milestones

Initiated BLA rolling submission to the FDA for axicabtagene ciloleucel in December 2016.
Received Orphan Drug Designation from the FDA for KTE-C19 in the treatment of five additional B-cell malignancies, granting Kite the designation for the major indications in hematologic malignancies in the US. KTE-C19 also has Orphan Drug Designation in the EU for these indications.
Received Priority Medicines (PRIME) status from the European Medicines Agency for KTE-C19 in the treatment of chemorefractory DLBCL.
Axicabtagene Ciloleucel Commercial & Manufacturing Readiness

Achieved 99 percent success rate in the manufacturing of clinical product patient dose from a single apheresis for the multi-center ZUMA-1 clinical trial.
Marked the official opening of Kite’s commercial manufacturing plant, a state-of-the-art facility in El Segundo, California estimated to have the capacity to produce more than 4,000 patient therapies per year.
Initiated development of Kite Konnect, a cloud-based solution for commercial-scale ordering, logistics, monitoring and delivery of T-cell therapies, designed to enable a positive prescriber and patient experience.
Pipeline Expansion and Developments

Submitted an investigational new drug (IND) application for KITE-718, a TCR product candidate that targets MAGE-A3/A6 antigens expressed on solid tumors.
Initiated plans to file an IND application in 2017 for KITE-585, a CAR product candidate targeting B cell maturation antigen (BCMA) for multiple myeloma.
Initiated plans to file IND applications in 2018 for KITE-796, a CAR product candidate targeting CLL-1 in acute myeloid leukemia (AML), and for KITE-439, a TCR product candidate targeting human papillomavirus (HPV)-16 E7 for cervical cancer, head and neck cancer, and other solid tumors.
Strategic Collaborations

Entered into a new Cooperative Research and Development Agreement (CRADA) for the development of a fully human anti-CD19 CAR product candidate to treat B-cell malignancies with the National Cancer Institute (NCI).
Licensed intellectual property related to a fully human anti-CD19 CAR to treat B-cell malignancies from the National Institutes of Health (NIH).
Expanded the TCR portfolio by licensing intellectual property from the NIH related to multiple TCR product candidates for the treatment of solid tumors expressing mutated KRAS antigens.
Entered into a new CRADA for the development of TCR product candidates directed against HPV-16 E6 and E7 for the treatment of HPV-associated cancers with the NCI.
Licensed a technology platform from The Regents of the University of California, on behalf of the University of California, Los Angeles, for the scalable production of T cells using pluripotent stem cell lines capable of indefinite self-renewal and designed to overcome limitations of current allogeneic approaches.
Partnered with Leiden University Medical Center to develop TCR product candidates targeting solid tumors associated with HPV-16 infection.

FDA Accepts the Biologics License Application for Avelumab for the Treatment of Metastatic Urothelial Carcinoma for Priority Review

On February 28, 2017 EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the US and Canada, and Pfizer Inc. reported that the US Food and Drug Administration (FDA) has accepted for Priority Review EMD Serono’s Biologics License Application (BLA) for avelumab* as a treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC) with disease progression on or after platinum-based therapy (Press release, Pfizer, FEB 28, 2017, View Source [SID1234517878]). The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2017, for avelumab in this indication.

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"Taken together with last year’s filing for metastatic Merkel cell carcinoma, this BLA acceptance confirms our rapid and continued progress in the clinical development of avelumab," said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the biopharma business of Merck KGaA, Darmstadt, Germany. "We continue to evaluate avelumab in cancers that have limited or suboptimal treatment choices, such as metastatic or locally advanced urothelial carcinoma, to hopefully be able to provide patients with new treatment options for fighting their disease."

Despite advances in the treatment of UC, the prognosis for patients remains poor, particularly when the disease has metastasized. Bladder cancer makes up approximately 90% of urothelial cancers and is the sixth most common cancer in the US.[1],[2] "

Advanced urothelial carcinoma remains a difficult-to-treat tumor, which is why we are developing a comprehensive clinical development program that involves Phase I and III trials designed to address this challenge," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "We’re continuing to accelerate our urothelial carcinoma development program and look forward to continuing our dialogue with the FDA."

Avelumab is an investigational, fully human anti-PD-L1 antibody. The FDA’s Priority Review status reduces the review time from 10 months to a goal of six months from the day of filing acceptance and is given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists. In November 2016, the FDA accepted, and granted Priority Review status to, the BLA for avelumab for the treatment of patients with metastatic Merkel cell carcinoma.

The international clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs, including nine Phase III trials, and more than 4,000 patients evaluated across more than 15 tumor types. In December 2015, Merck KGaA, Darmstadt, Germany, and Pfizer announced the initiation of a Phase III study (JAVELIN Bladder 100) of avelumab in the first-line setting as a maintenance treatment in patients with locally advanced or metastatic UC. This trial is currently enrolling patients.

*Avelumab is not approved for any indication in any market. This marks the second acceptance of an application by the FDA to review the investigational product, avelumab.

References

1.National Comprehensive Cancer Network. NCCN Guidelines Version 1.2017 Updates. Bladder Cancer. Available from: View Source (link is external). Last Accessed: February 2017.

2.Siegel RL, et al. Cancer Statistics, 2017. CA Cancer J Clin 2017;67:7-30. Available from: View Source (link is external). Last Accessed: February 2017.

3.American Cancer Society. Key Statistics for Bladder Cancer. Available from: View Source (link is external). Last Accessed: February 2017.

About Metastatic Urothelial Carcinoma

Urothelial Carcinoma includes several tumors originating from the cells lining the bladder, renal pelvis and urethra. While cancers outside of the bladder are relatively uncommon, accounting for an estimated 10% of cases, bladder cancer represents 90% of urothelial cancers and is the ninth most common cancer globally.[1],[3] Worldwide, approximately 400,000 new cases of bladder cancer are diagnosed and 150,000 deaths are attributed to this disease each year.[3] The incidence and mortality of bladder cancer have remained unchanged over the past 25 years.[3]

About Avelumab

Avelumab is a fully human antibody specific for a protein found on tumor cells called PD-L1, or programmed death ligand-1. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab. Common adverse reactions include fatigue, musculoskeletal pain, diarrhea, nausea peripheral edema, decreased appetite, and rash. Immune-mediated adverse reactions have also been reported.

Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US

Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an investigational anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.