|By Marketwired .||
|December 10, 2012 04:00 PM EST||
TUSTIN, CA -- (Marketwire) -- 12/10/12 -- Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a biopharmaceutical company developing first-in-class monoclonal antibodies focused on the treatment and diagnosis of cancer, today announced financial results for the second quarter ended October 31, 2012 of fiscal year (FY) 2013 and provided an update on its advancing clinical pipeline and other corporate developments.
"Certainly the recent highlight for Peregrine is the agreement reached with the FDA that provides a clear pathway for advancing our Cotara program into a pivotal registration trial in patients with brain cancer. This milestone is the result of a significant amount of work and collaboration with the FDA of which we are particularly proud given the potential for this novel treatment in this difficult to treat disease," said Steven W. King, president and chief executive officer of Peregrine. "This was also a very strong quarter for our manufacturing subsidiary, Avid Bioservices, as we are on track for another record year of manufacturing revenues. We are also making steady progress in advancing the bavituximab program on multiple clinical fronts with important clinical milestones anticipated to occur over the coming months. Upcoming clinical milestones for the program include key median overall survival endpoints in pancreatic and front-line non-small cell lung cancer and final results from our second-line non-small cell lung cancer study in which we discovered discrepancies and have subsequently been intensely reviewing. The goal of this review is to be able to generate a final data set that we believe could be used to support advancing the program into a pivotal trial."
COTARA PROGRAM HIGHLIGHTS
Peregrine announced that it has reached agreement with the U.S. Food and Drug Administration (FDA) on the design of a single registration trial for Cotara in patients with recurrent glioblastoma multiforme (GBM) following an end-of-Phase II meeting. The FDA has agreed with the company's proposed randomized trial design evaluating two dose levels of Cotara in up to 300 patients. The trial design allows for multiple interim data analyses with the potential to stop patient accrual early based on predicted success or futility. The company plans to seek partners both in the U.S. and internationally to support the development of Cotara for this deadly form of brain cancer. Cotara has been granted orphan drug status and Fast Track designation for the treatment of GBM and anaplastic astrocytoma by the FDA and orphan drug designation by the European Medicines Agency (EMA).
BAVITUXIMAB CLINICAL TRIALS
Peregrine currently has eight ongoing clinical trials as follows:
- Peregrine continues to conduct a detailed internal review into the discrepancies tied to the randomized, double-blind placebo-controlled Phase II trial of bavituximab in second-line non-small cell lung cancer (NSCLC), that were discovered as part of the routine collection of data in advance of the company's end-of-Phase II meeting with regulatory authorities. The goal of this review is to gain a thorough understanding of the events leading up to, including and following the patient treatment group assignments and investigational drug coding and distribution. This review includes the testing of investigational product, patient samples, reviewing the operations of multiple vendors, among other activities. Investors are reminded not to rely on clinical data that the company disclosed on or before September 7, 2012 regarding this trial.
- Randomized Phase II clinical trial evaluating bavituximab plus carboplatin and paclitaxel versus carboplatin and paclitaxel alone in 83 evaluable patients with previously untreated Stage IIIb or Stage IV NSCLC. Patient enrollment was completed in September of 2011. A secondary endpoint in the trial, median overall survival (OS), is an event-driven endpoint and will be reported once mature.
- Randomized Phase II clinical trial evaluating bavituximab plus gemcitabine versus gemcitabine alone in 70 patients with previously untreated Stage IV pancreatic cancer. Patient enrollment was completed in June 2012. The primary endpoint in the trial, median OS, is an event-driven endpoint and will be reported once mature.
- Phase I/II Investigator Sponsored Trial (IST) evaluating bavituximab in combination with sorafenib in up to 48 patients with advanced hepatocellular carcinoma (liver cancer). The Phase I portion of the trial has completed patient enrollment with enrollment in the Phase II portion of the trial ongoing.
- Phase I/II IST evaluating bavituximab in combination with cabazitaxel in up to 31 patients with second-line castration-resistant prostate cancer.
- Phase Ib IST evaluating bavituximab in combination with carboplatin and pemetrexed in up to 25 patients with previously untreated Stage IV NSCLC.
- Phase I IST evaluating bavituximab in combination with paclitaxel in up to 14 patients with HER2-negative metastatic breast cancer.
- Phase I IST evaluating bavituximab in combination with capecitabine and radiation therapy in up to 18 patients with Stage II or III rectal adenocarcinoma.
PS-TARGETING MOLECULAR IMAGING PROGRAM HIGHLIGHTS
Peregrine continues to enroll and dose up to 12 patients in an open-label, single-center trial of its experimental phosphatidylserine (PS)-targeting molecular imaging candidate, 124I-PGN650, in patients with various solid tumor types. The primary goal of the trial is to estimate radiation dosimetry in critical and non-critical organs. Secondary objectives of the trial are tumor imaging and safety.
PRECLINICAL DEVELOPMENT HIGHLIGHTS
In October, at the 27th Annual Meeting of the Society for Immunotherapy of Cancer, data were presented demonstrating the ability of the company's PS-targeting antibodies to stimulate cancer fighting immune responses. Additionally, data were published in the peer-reviewed journal Nuclear Medicine and Biology highlighting results from a study investigating the company's fully human phosphatidylserine (PS)-targeting antibody PGN635 utilized as a radiolabeled tumor imaging probe. The results demonstrate the potential breadth of applicability of the company's PS-targeting antibodies to clearly image solid tumors regardless of cancer type, and provide a potential method to rapidly assess the anti-tumor efficacy of chemotherapies and other approved and experimental cancer treatments
Total revenues for the second quarter of FY 2013 were $6,139,000 compared to $4,232,000, for the same quarter of the prior fiscal year. This increase was primarily attributable to contract manufacturing revenue generated by Peregrine's biomanufacturing subsidiary Avid Bioservices, which generated contract manufacturing revenue of $6,061,000 for the second quarter of FY 2013, compared to $4,154,000 for the same quarter of the prior fiscal year. The increase in contract manufacturing revenue was primarily due to a greater number of completed manufacturing runs being released and shipped during the current quarter. Based on current manufacturing commitments from Avid's third-party clients for services to be provided during the remainder of FY 2013, we expect contract manufacturing revenue to be at least $18 million for FY 2013. In addition, Avid will continue to utilize available capacity and resources to continue its preparation for later stage clinical development and potential commercialization of bavituximab and Cotara, while also seeking to grow its services from third-party clients.
Total costs and expenses decreased $3,072,000 to $13,196,000 in the second quarter of FY 2013 from $16,268,000 in the second quarter of FY 2012. This decrease was primarily attributable to lower research and development expenses associated with a decrease in clinical trial costs. For the second quarter of FY 2013, cost of contract manufacturing and research and development expenses were $3,703,000 and $6,053,000, respectively, compared to $3,718,000 and $9,818,000, respectively, for the second quarter of FY 2012. Selling, general and administrative expenses for the second quarter of FY 2013 were $3,440,000 compared to $2,732,000 in the second quarter of FY 2012.
Peregrine's consolidated net loss was $8,753,000, or $0.08 per basic and diluted share, for the second quarter of FY 2013, compared to a net loss of $12,055,000, or $0.16 per basic and diluted share, for the same quarter of the prior year.
Peregrine reported $24,443,000 in cash and cash equivalents at October 31, 2012, compared to $18,991,000 at July 31, 2012. From the period of September 27, 2012 through October 31, 2012, the company raised $16.2 million in net proceeds in order to replace the initial funding it repaid on September 25, 2012 under a loan facility dated August 30, 2012. The funds were raised under an At Market Sales Issuance Agreement with McNicoll, Lewis & Vlak LLC at an average price per share of $0.90. The company issued no warrants in connection with the At Market Sales Issuance Agreement.
More detailed financial information and analysis may be found in Peregrine's Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today.
Peregrine will host a conference call and webcast this afternoon, December 10, 2012, at 4:30 PM EST (1:30 PM PST).
To listen to the conference call, please dial (877) 312-5443 or (253) 237-1126 and request the Peregrine Pharmaceuticals conference call. A replay of the call will be available starting approximately two hours after the conclusion of the call through December 24, 2012 by calling (855) 859-2056, or (404) 537-3406 and using passcode 75630640.
To listen to the live webcast, or access the archived webcast, please visit: http://ir.peregrineinc.com/events.cfm
About Peregrine Pharmaceuticals, Inc.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials focused on the treatment and diagnosis of cancer. The company is pursuing multiple clinical programs in cancer with its lead product candidate bavituximab and novel brain cancer agent Cotara®. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that data from a Cotara pivotal trial may not support BLA submission or registration, the risk that the company does not have, or is unable to raise, sufficient capital to fund a pivotal trial and the risk that the company is unable to find a suitable partner to advance the Cotara program, the risk that final data from the randomized, double-blind, placebo-controlled Phase IIb may never support future development in second-line NSCLC, the risks associated with the recently filed class action lawsuits or potential regulatory investigations due to the uncertainty created by the above referenced discrepancies, the risk that results from the other randomized Phase II trial will not be consistent with results experienced in the earlier single-arm Phase II trial or support registration filings with the FDA, the risk that Avid's revenue growth may slow or decline, the risk that Avid may experience technical difficulties in processing customer orders which could delay delivery of products to customers and receipt of payment, and the risk that one or more existing Avid customers, including those with committed manufacturing or representing its backlog, terminates its contract prior to completion. It is important to note that the Company's actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the our SEC reports including, but not limited to, the annual report on Form 10-K for the fiscal year ended April 30, 2012 and quarterly report on Form 10-Q for the quarter ended October 31, 2012. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.
PEREGRINE PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS Three Months Ended Six Months Ended October 31, October 31, 2012 2011 2012 2011 ------------ ------------ ------------ ------------ Unaudited Unaudited Unaudited Unaudited REVENUES: Contract manufacturing revenue $ 6,061,000 $ 4,154,000 $ 10,196,000 $ 9,593,000 License revenue 78,000 78,000 194,000 294,000 ------------ ------------ ------------ ------------ Total revenues 6,139,000 4,232,000 10,390,000 9,887,000 COSTS AND EXPENSES: Cost of contract manufacturing 3,703,000 3,718,000 5,727,000 6,735,000 Research and development 6,053,000 9,818,000 13,034,000 17,578,000 Selling, general and administrative 3,440,000 2,732,000 6,357,000 5,661,000 ------------ ------------ ------------ ------------ Total costs and expenses 13,196,000 16,268,000 25,118,000 29,974,000 ------------ ------------ ------------ ------------ LOSS FROM OPERATIONS (7,057,000) (12,036,000) (14,728,000) (20,087,000) ------------ ------------ ------------ ------------ OTHER INCOME (EXPENSE): Interest and other income 44,000 9,000 52,000 22,000 Interest and other expense (44,000) (28,000) (45,000) (82,000) Loss on early extinguishment of debt (1,696,000) - (1,696,000) - ------------ ------------ ------------ ------------ NET LOSS $ (8,753,000) $(12,055,000) $(16,417,000) $(20,147,000) ============ ============ ============ ============ WEIGHTED AVERAGE COMMON SHARES OUTSTANDING: Basic and Diluted 109,405,778 77,523,005 106,344,857 74,089,786 ============ ============ ============ ============ BASIC AND DILUTED LOSS PER COMMON SHARE $ (0.08) $ (0.16) $ (0.15) $ (0.27) ============ ============ ============ ============ COMPREHENSIVE LOSS $ (8,753,000) $(12,055,000) $(16,417,000) $(20,147,000) ============ ============ ============ ============ PEREGRINE PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS OCTOBER 31, APRIL 30, 2012 2012 ------------- ------------- Unaudited ASSETS CURRENT ASSETS: Cash and cash equivalents $ 24,443,000 $ 18,033,000 Trade and other receivables, net 2,320,000 2,353,000 Inventories, net 5,426,000 3,611,000 Prepaid expenses and other current assets, net 885,000 795,000 ------------- ------------- Total current assets 33,074,000 24,792,000 Property, net 2,683,000 2,900,000 Other assets 771,000 570,000 ------------- ------------- TOTAL ASSETS $ 36,528,000 $ 28,262,000 ============= ============= LIABILITIES AND STOCKHOLDERS' EQUITY CURRENT LIABILITIES: Accounts payable $ 3,176,000 $ 3,492,000 Accrued clinical trial and related fees 1,558,000 2,111,000 Accrued payroll and related costs 2,394,000 2,468,000 Deferred revenue 6,221,000 3,651,000 Customer deposits 8,500,000 4,865,000 Other current liabilities 1,083,000 1,052,000 ------------- ------------- Total current liabilities 22,932,000 17,639,000 Deferred revenue 205,000 361,000 Other long-term liabilities 721,000 779,000 Commitments and contingencies STOCKHOLDERS' EQUITY: Preferred stock-$0.001 par value; authorized 5,000,000 shares; non-voting; nil shares outstanding - - Common stock-$0.001 par value; authorized 325,000,000 shares; outstanding - 123,310,188 and 101,421,365, respectively 123,000 101,000 Additional paid-in capital 367,088,000 347,506,000 Accumulated deficit (354,541,000) (338,124,000) ------------- ------------- Total stockholders' equity 12,670,000 9,483,000 ------------- ------------- TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY $ 36,528,000 $ 28,262,000 ============= =============
Christopher Keenan or Jay Carlson
Peregrine Pharmaceuticals, Inc.
Microservices are a very exciting architectural approach that many organizations are looking to as a way to accelerate innovation. Microservices promise to allow teams to move away from monolithic "ball of mud" systems, but the reality is that, in the vast majority of organizations, different projects and technologies will continue to be developed at different speeds. How to handle the dependencies between these disparate systems with different iteration cycles? Consider the "canoncial problem" in this scenario: microservice A (releases daily) depends on a couple of additions to backend B (re...
Nov. 25, 2015 10:00 PM EST Reads: 377
I recently attended and was a speaker at the 4th International Internet of @ThingsExpo at the Santa Clara Convention Center. I also had the opportunity to attend this event last year and I wrote a blog from that show talking about how the “Enterprise Impact of IoT” was a key theme of last year’s show. I was curious to see if the same theme would still resonate 365 days later and what, if any, changes I would see in the content presented.
Nov. 25, 2015 09:00 PM EST Reads: 359
Apps and devices shouldn't stop working when there's limited or no network connectivity. Learn how to bring data stored in a cloud database to the edge of the network (and back again) whenever an Internet connection is available. In his session at 17th Cloud Expo, Ben Perlmutter, a Sales Engineer with IBM Cloudant, demonstrated techniques for replicating cloud databases with devices in order to build offline-first mobile or Internet of Things (IoT) apps that can provide a better, faster user experience, both offline and online. The focus of this talk was on IBM Cloudant, Apache CouchDB, and ...
Nov. 25, 2015 08:30 PM EST Reads: 361
Container technology is shaping the future of DevOps and it’s also changing the way organizations think about application development. With the rise of mobile applications in the enterprise, businesses are abandoning year-long development cycles and embracing technologies that enable rapid development and continuous deployment of apps. In his session at DevOps Summit, Kurt Collins, Developer Evangelist at Built.io, examined how Docker has evolved into a highly effective tool for application delivery by allowing increasingly popular Mobile Backend-as-a-Service (mBaaS) platforms to quickly crea...
Nov. 25, 2015 05:00 PM EST Reads: 300
Discussions of cloud computing have evolved in recent years from a focus on specific types of cloud, to a world of hybrid cloud, and to a world dominated by the APIs that make today's multi-cloud environments and hybrid clouds possible. In this Power Panel at 17th Cloud Expo, moderated by Conference Chair Roger Strukhoff, panelists addressed the importance of customers being able to use the specific technologies they need, through environments and ecosystems that expose their APIs to make true change and transformation possible.
Nov. 25, 2015 04:15 PM EST Reads: 475
With major technology companies and startups seriously embracing IoT strategies, now is the perfect time to attend @ThingsExpo 2016 in New York and Silicon Valley. Learn what is going on, contribute to the discussions, and ensure that your enterprise is as "IoT-Ready" as it can be! Internet of @ThingsExpo, taking place Nov 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 17th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The Internet of Things (IoT) is the most profound cha...
Nov. 25, 2015 02:45 PM EST Reads: 493
Internet of @ThingsExpo, taking place June 7-9, 2016 at Javits Center, New York City and Nov 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with the 18th International @CloudExpo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world and ThingsExpo New York Call for Papers is now open.
Nov. 25, 2015 02:30 PM EST Reads: 505
The cloud. Like a comic book superhero, there seems to be no problem it can’t fix or cost it can’t slash. Yet making the transition is not always easy and production environments are still largely on premise. Taking some practical and sensible steps to reduce risk can also help provide a basis for a successful cloud transition. A plethora of surveys from the likes of IDG and Gartner show that more than 70 percent of enterprises have deployed at least one or more cloud application or workload. Yet a closer inspection at the data reveals less than half of these cloud projects involve production...
Nov. 25, 2015 02:15 PM EST Reads: 424
Growth hacking is common for startups to make unheard-of progress in building their business. Career Hacks can help Geek Girls and those who support them (yes, that's you too, Dad!) to excel in this typically male-dominated world. Get ready to learn the facts: Is there a bias against women in the tech / developer communities? Why are women 50% of the workforce, but hold only 24% of the STEM or IT positions? Some beginnings of what to do about it! In her Day 2 Keynote at 17th Cloud Expo, Sandy Carter, IBM General Manager Cloud Ecosystem and Developers, and a Social Business Evangelist, wil...
Nov. 25, 2015 02:00 PM EST Reads: 511
Cloud computing delivers on-demand resources that provide businesses with flexibility and cost-savings. The challenge in moving workloads to the cloud has been the cost and complexity of ensuring the initial and ongoing security and regulatory (PCI, HIPAA, FFIEC) compliance across private and public clouds. Manual security compliance is slow, prone to human error, and represents over 50% of the cost of managing cloud applications. Determining how to automate cloud security compliance is critical to maintaining positive ROI. Raxak Protect is an automated security compliance SaaS platform and ma...
Nov. 25, 2015 02:00 PM EST Reads: 352
In his keynote at @ThingsExpo, Chris Matthieu, Director of IoT Engineering at Citrix and co-founder and CTO of Octoblu, focused on building an IoT platform and company. He provided a behind-the-scenes look at Octoblu’s platform, business, and pivots along the way (including the Citrix acquisition of Octoblu).
Nov. 25, 2015 01:30 PM EST Reads: 465
There are over 120 breakout sessions in all, with Keynotes, General Sessions, and Power Panels adding to three days of incredibly rich presentations and content. Join @ThingsExpo conference chair Roger Strukhoff (@IoT2040), June 7-9, 2016 in New York City, for three days of intense 'Internet of Things' discussion and focus, including Big Data's indespensable role in IoT, Smart Grids and Industrial Internet of Things, Wearables and Consumer IoT, as well as (new) IoT's use in Vertical Markets.
Nov. 25, 2015 12:00 PM EST Reads: 517
Today air travel is a minefield of delays, hassles and customer disappointment. Airlines struggle to revitalize the experience. GE and M2Mi will demonstrate practical examples of how IoT solutions are helping airlines bring back personalization, reduce trip time and improve reliability. In their session at @ThingsExpo, Shyam Varan Nath, Principal Architect with GE, and Dr. Sarah Cooper, M2Mi’s VP Business Development and Engineering, explored the IoT cloud-based platform technologies driving this change including privacy controls, data transparency and integration of real time context with p...
Nov. 25, 2015 12:00 PM EST Reads: 364
The Internet of Things (IoT) is growing rapidly by extending current technologies, products and networks. By 2020, Cisco estimates there will be 50 billion connected devices. Gartner has forecast revenues of over $300 billion, just to IoT suppliers. Now is the time to figure out how you’ll make money – not just create innovative products. With hundreds of new products and companies jumping into the IoT fray every month, there’s no shortage of innovation. Despite this, McKinsey/VisionMobile data shows "less than 10 percent of IoT developers are making enough to support a reasonably sized team....
Nov. 25, 2015 10:00 AM EST Reads: 429
We all know that data growth is exploding and storage budgets are shrinking. Instead of showing you charts on about how much data there is, in his General Session at 17th Cloud Expo, Scott Cleland, Senior Director of Product Marketing at HGST, showed how to capture all of your data in one place. After you have your data under control, you can then analyze it in one place, saving time and resources.
Nov. 25, 2015 09:45 AM EST Reads: 115
Just over a week ago I received a long and loud sustained applause for a presentation I delivered at this year’s Cloud Expo in Santa Clara. I was extremely pleased with the turnout and had some very good conversations with many of the attendees. Over the next few days I had many more meaningful conversations and was not only happy with the results but also learned a few new things. Here is everything I learned in those three days distilled into three short points.
Nov. 25, 2015 09:00 AM EST Reads: 268
As organizations realize the scope of the Internet of Things, gaining key insights from Big Data, through the use of advanced analytics, becomes crucial. However, IoT also creates the need for petabyte scale storage of data from millions of devices. A new type of Storage is required which seamlessly integrates robust data analytics with massive scale. These storage systems will act as “smart systems” provide in-place analytics that speed discovery and enable businesses to quickly derive meaningful and actionable insights. In his session at @ThingsExpo, Paul Turner, Chief Marketing Officer at...
Nov. 25, 2015 08:15 AM EST Reads: 350
DevOps is about increasing efficiency, but nothing is more inefficient than building the same application twice. However, this is a routine occurrence with enterprise applications that need both a rich desktop web interface and strong mobile support. With recent technological advances from Isomorphic Software and others, rich desktop and tuned mobile experiences can now be created with a single codebase – without compromising functionality, performance or usability. In his session at DevOps Summit, Charles Kendrick, CTO and Chief Architect at Isomorphic Software, demonstrated examples of com...
Nov. 25, 2015 07:45 AM EST Reads: 345
In his General Session at 17th Cloud Expo, Bruce Swann, Senior Product Marketing Manager for Adobe Campaign, explored the key ingredients of cross-channel marketing in a digital world. Learn how the Adobe Marketing Cloud can help marketers embrace opportunities for personalized, relevant and real-time customer engagement across offline (direct mail, point of sale, call center) and digital (email, website, SMS, mobile apps, social networks, connected objects).
Nov. 25, 2015 07:30 AM EST Reads: 251
The Internet of Everything is re-shaping technology trends–moving away from “request/response” architecture to an “always-on” Streaming Web where data is in constant motion and secure, reliable communication is an absolute necessity. As more and more THINGS go online, the challenges that developers will need to address will only increase exponentially. In his session at @ThingsExpo, Todd Greene, Founder & CEO of PubNub, exploreed the current state of IoT connectivity and review key trends and technology requirements that will drive the Internet of Things from hype to reality.
Nov. 25, 2015 05:45 AM EST Reads: 381