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Q1 2019 Regenxbio Inc Earnings Call
Rockville Jun 3, 2019 (Thomson StreetEvents) -- Edited Transcript of Regenxbio Inc earnings conference call or presentation Tuesday, May 7, 2019 at 8:30:00pm GMT
TEXT version of Transcript
Corporate Participants
* Kenneth T. Mills
REGENXBIO Inc. - CEO, President & Director
* Patrick J. Christmas
REGENXBIO Inc. - Senior VP & General Counsel
* Steve Pakola
* Vittal K. Vasista
REGENXBIO Inc. - CFO
Conference Call Participants
* Gena Wang
Barclays Bank PLC, Research Division - Research Analyst
* Joshua Elliott Schimmer
Evercore ISI Institutional Equities, Research Division - Senior MD & Equity Analyst
* Mani Foroohar
SVB Leerink LLC, Research Division - MD of Genetic Medicines & Senior Research Analyst
* Matthew Kelsey Harrison
Morgan Stanley, Research Division - Executive Director
Operator [1]
Good afternoon and welcome to the REGENXBIO First Quarter 2019 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be given at that time. As a reminder, this conference call is being recorded.
I would now like to turn the call over to Mr. Patrick Christmas, Senior Vice President and General Counsel for REGENXBIO. You may begin.
Patrick J. Christmas, REGENXBIO Inc. - Senior VP & General Counsel [2]
Good afternoon and thank you for joining us today. With us today are Ken Mills, REGENXBIO's President and Chief Executive Officer; Steve Pakola, our Chief Medical Officer and Vit Vasista, our Chief Financial Officer.
Earlier this afternoon, REGENXBIO released financial and operating results for the 3 months ended March 31, 2019. The press release reporting our financial results is available on our website at www.regenxbio.com.
Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend and other words of similar meaning. Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties. These risks are described in the risk factors and the Management's Discussion and Analysis sections of REGENXBIO's filings with the Securities and Exchange Commission which are available on the SEC's website.
Any information we provide on this conference call is provided only as of the date of this call May 7, 2019 and we undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events or otherwise. Please be advised that today's call is being recorded and webcast. In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company. Actual results may differ materially.
I would now like to turn the call over to Ken Mills, President and Chief Executive Officer of REGENXBIO.
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [3]
Thank you, Patrick, and good afternoon everyone and thanks for joining us. On today's conference call, we will provide a recap of our recent progress in the advancement of our NAV Technology Platform and the continued progress of our internal product candidates. Steve will provide an update on our clinical programs and Vit will provide an update on financial results for the first quarter of 2019. At the end, we'll open the call for questions.
At REGENXBIO, our mission is clear. We seek to improve lives through the curative potential of gene therapy based on our proprietary NAV Technology Platform. We believe single administration gene therapy treatments can significantly alter the course of genetic diseases and diseases broadly affecting public health and we are committed to our research and development of gene therapies with patients in mind.
Our NAV Technology Platform consists of over 100 novel adeno-associated viral vectors or AAV vectors including AAV7, AAV8, AAV9 and AAVrh10. REGENXBIO's novel and unique approach to gene therapy focuses on enabling cells in the body to produce therapeutic proteins or antibodies and targeting and correcting genetic defects. Our product candidates have the potential to change the course of the disease and deliver improved patient outcomes in therapeutic areas where significant unmet medical needs remain and they're designed to provide long-lasting clinical benefit.
Our NAV Technology serves as a backbone gene therapy research and is widely utilized gene therapy platform across diverse disease applications. We selectively license components of our NAV Technology Platform to third-party companies whose vision and commitment to gene therapy is aligned with our own. Our internal product candidates are being developed across the spectrum of therapeutic areas. In retinal diseases our gene therapy product candidate encodes for our continuous long term expression of an antibody and can potentially help treat millions of patients around the world. Additionally, we are advancing 4 internal product candidates for rare genetic diseases that cause neurodegeneration and metabolic disorders. The REGENXBIO NAV Technology Platform has now been used to treat over 200 patients in various clinical trials including our NAV Technology licensee network.
Before I turn the call over to Steve to provide an update on our lead product candidates, I want to highlight that this year marks the 10th anniversary of our founding. Over the past 10 years, we've enabled incredible progress in the advancement of gene therapy. REGENXBIO's own formula for success has always been driven by breakthrough science, talented people, sound capital and disciplined execution of our plans. Our decade of commitment to make gene therapy a reality for patients has transformed us into a global leader in developing gene therapies that have the potential to transform the way diseases are treated. Today, our efforts stretch far beyond their own internal programs with numerous licensees sharing our determination to make effective gene therapy a reality.
None of this would have been possible without the continued support of the individuals participating in our clinical trials, their families and the numerous patient advocacy groups with whom we work. Next week on May 15, we will join the National MPS Society in celebration of MPS Awareness Day. We support their important work to recognize all the children and adults diagnosed with mucopolysaccharidosis diseases in their efforts to advocate for MPS awareness in the support of the advancement of new treatments.
With that, I'd now like to turn the call over to Dr. Steve Pakola, our newly appointed Chief Medical Officer, to give an update on our lead product candidates. Steve joins our team from Aerpio Pharmaceuticals where he was Chief Medical Officer. While Dr. Pakola's experience encompasses multiple therapeutic areas, his predominant focus has been the development of treatments for retinal disorders including clinical development experience in diabetic retinopathy, diabetic macular edema and age-related macular degeneration. Steve, we're really excited to have you as part of the team.
Steve Pakola, [4]
Thanks, Ken. First, I'd like to say that I'm thrilled to join the REGENXBIO team. It's a time of exciting momentum for the company as we advance our breakthrough science with curative potential for both rare diseases and diseases that broadly impact public health. As a reminder, our lead product candidates are currently targeting the following indications, wet age-related macular degeneration or wet AMD, mucopolysaccharidosis type I and type II or MPS I and II, homozygous familial hypercholesterolemia or HoFH and late infantile neuronal ceroid lipofuscinosis type II disease or CLN2 disease, a form of Batten disease.
I'll begin with our RGX-314 program for the treatment of wet AMD, a disease that affects more than 2 million patients in the U.S., Europe and Japan. Patients with wet AMD usually require anti-VEGF therapy as frequently as every month indefinitely to prevent vision loss. Continuing a long-term therapy with intraocular anti-VEGF injections is a burden to patients and families and many patients struggle to comply with the recommended therapeutic regimen, leading to under treatment and ultimately vision loss over time. RGX-314 utilizes the NAV AAV8 vector, which encompasses a gene that is introduced into retinal cells where it is designed to encode for the long-term continuous expression of a therapeutic anti-VEGF protein. The expressed anti-VEGF antibody fab or antibody fragment potentially halts the proliferation of blood vessels in the retina, the hallmark of wet AMD. The NAV AAV8 vector has been selected for this product candidate, because it has demonstrated effective transduction of retinal cells and the ability to produce and sustain high levels of therapeutic protein over the long term in multiple pre-clinical animal models.
Today we reported that Cohort 5 is nearing completion at a dose of 2.5x10^11 genome copies per eye in the Phase 1/2a trial of RGX-314 and that RGX-314 continues to be well tolerated across all cohorts with no drug-related serious adverse events reported. We previously reported that completed enrollment of Cohort 4 at a dose of 1.6x10^11 genome copies per eye. Additionally today we reported new assessments of efficacy for Cohort 3 at 1 year after the administration of study drug at a dose of 6x10^10 genome copies per eye. As a reminder, leading up to trial enrollment subjects in the trial had received on average more than 35 anti-VEGF injections over 5 years.
At 1 year following the administration of RGX-314, Cohort 3 subjects continue to receive a low number of anti-VEGF injections following the administration of RGX-314 along with sustained and durable intraocular protein expression. A persistent clinical durability of effect was observed on best corrected visual acuity or BCVA and central retinal thickness or CRT for subjects in Cohort 3. Mean BCVA improved by 5 letters and mean CRT decreased or improved by 39 microns, from baseline at 1 year in these subjects. Furthermore, 50% of subjects treated in Cohort 3 continued to remain free of any anti-VEGF injections through 1 year with a mean BCVA improvement of 10 letters and a mean CRT decrease of 59 microns from baseline at 1 year in these subjects. These results provide evidence that one-time treatment with RGX-314 can achieve sustained duration of effect reaching at least 1 year in wet AMD patients. We expect to present top line data by the end of 2019 and we are on track to initiate a larger, randomized, controlled Phase 2b trial for wet AMD in late 2019. Today we also announced our plans to extend RGX-314 into an additional chronic retinal condition diabetic retinopathy. As background diabetic retinopathy or DR is the leading cause of visual impairment including blindness in the working-age population. Patients with DR often present with vision loss at a younger age than patients with macular degeneration. In the U.S. alone DR affects approximately 8 million people. DR is a complication of diabetes mellitus caused by damaged blood vessels in the retina. It is a progressive retinopathy, the severity of which ranges from mild non-proliferative DR to a more advanced proliferative stage. The main causes of vision loss secondary to DR are the vision threatening complications of proliferative DR marked by abnormal new vessels and scar formation, as well as diabetic macular edema which is characterized by the breakdown of retinal blood vessel walls, resulting in the leakage of fluid and proteins in the retina. The progression of DR and its complications leading to vision impairment are largely driven by excess intraocular VEGF. The standard of care for vision threatening complications of diabetic eye disease is frequent intraocular injections of drugs that target VEGG on a long-term basis and/or a panretinal laser treatment depending on the stage of the disease.
We are excited about the potential for RGX-314 to address significant unmet needs in diabetic eye disease. The administration of a onetime therapy that could potentially halt disease progression and treat related vision threatening complications could transform the lives of patients who are currently burdened by numerous ongoing visits to multiple specialists. For our planned Phase II trial evaluating RGX-314 for the treatment of DR, we expect to administer the treatment using the same subretinal approach as the current Phase 1 2a trial evaluating RGX-314 for the treatment of wet AMD. Safety data from this ongoing trial will be used to support dose selection. We expect to include many of our existing wet AMD sites along with additional sites in the Phase II trial for DR. Manufacturing is in the process to support enrollment in RGX-314 trials for both wet AMD and DR and we expect to file an IND for DR in the second half of 2019.
Next I'd like to turn to our programs and MPS I and II, which are lysosomal storage disorders caused by defects in the IDUA and IDS genes respectively. While approved and marketed enzyme replacement therapies do exist, they are indicated for the treatment of the systemic symptoms of MPS I and II, but do not address the CNS symptoms, which are associated with the most severe forms of these diseases. Our programs are designed to address this area of significant unmet need by utilizing the NAV AAV9 factor that will be administered directly into the cerebrospinal spinal fluid, via an intracisternal administration.
For RGX-121 for the treatment of MPS II to date one subject has been dosed in the first of 2 expected dose cohorts in the Phase I/II clinical trial. At the 28-week safety assessment RGX-121 continues to be well tolerated with no serious adverse events reported to date. Additional recruitment and site activation are ongoing and we expect to present an interim update from the Phase I/II clinical trial in the second half of 2019.
For RGX-111 for the treatment of MPS subject recruitment and additional site activations continue on the Phase I clinical trial. Under the current FDA protocol recruitment is focused on an initial subject of over 18 years of age. We expect to present an interim update from the Phase I clinical trial in the second half of 2019. Both RGX-121 and RGX-111 programs have received FDA Orphan Drug, Fast Track and Rare Pediatric Disease designations.
Turning to our metabolic disease program. We continue to execute on our RGX-501 program for the treatment of HoFH. HoFH is a rare genetic disorder caused by mutations in the gene encoding the low-density lipoprotein or LDL receptor. RGX-501 has the potential to address the underlying genetic defect responsible for HoFH by correcting the LDL receptor deficiency. Due to previously reported transaminase elevations 4 to 6 weeks post dosing in 3 subjects of Cohort 2, we amended our Phase I/II clinical protocol using corticosteroid prophylaxis and patient screening has reinitiated. We expect to report an interim update from Cohort 2 with corticosteroid prophylaxis from the Phase I/IIa clinical trial in the second half of 2019.
Finally, our RGX-181 program is being developed potentially halt progression of CLN2 disease, one of the most common forms of Batten disease, a rare pediatric neurodegenerative disease. We expect to file an IND or for an equivalent for the first in human clinical trial in the second half of 2019. The program has received FDA orphan drug and rare pediatric disease designations. We will continue our diligent work to drive these programs forward and we look forward to providing you with updates on our progress.
We continue to add to our capabilities and process development and manufacturing. We've recently produced our first GMP pulp drug substance based on our new suspension cell culture platform process. This bioreactor based process enables us to reach manufacturing scale suitable for future commercial production. Our process and analytical development team recently contributed several posters highlighting the advancement of several technologies at the ASGCT Meeting in Washington, D.C.
With that, I will turn the call back over to Ken. Ken??
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [5]
Thanks, Steve. We are very encouraged by these updates. REGENXBIO has an extensive footprint in the gene therapy space and our leadership and scientific innovation could potentially bring many breakthrough onetime gene therapy treatments to market with our own in-house lead candidates, as well as product candidates developed by our licensee network and enabled by REGENXBIO's NAV Technology.
As of March 31, 2019 our technology was being applied in more than 20 partnered product candidates in development by NAV Technology licensees and 14 of these partnered product candidates are in active clinical development, across a broad range of therapeutic areas in disease indications, including 2 clinical trials in hemophilia A, one sponsored by Bayer in partnership with Ultragenyx and one by Takeda.
Later this month, we anticipate FDA approval of Novartis' ZOLGENSMA for the treatment of spinal muscular atrophy or SMA Type 1 in the United States. This event will mark the first approval of a product based on NAV Technology. SMA Type 1 is a deadly neuromuscular disease commonly affecting young children. ZOLGENSMA could potentially provide new hope to patients and families suffering from SMA, and we are proud to be a contributor to this milestone through our license agreement with AveXis, now a wholly-owned subsidiary of Novartis.
ZOLGENSMA uses the NAV AAV9 vector. REGENXBIO expects to receive total milestone payments in the high single-digit millions upon U.S. and EU approval and is eligible to receive an additional $80 million in potential future commercial milestone payments. In addition, we will expect to receive mid-single to low double-digit royalties on worldwide net product sales. Earlier this week at the American Academy of Neurology Meeting in Philadelphia, Novartis presented interim data from their Phase I study of ZOLGENSMA in type II SMA and Phase III study designed to evaluate ZOLGENSMA in symptomatic SME newborns.
Intrathecal administration of ZOLGENSMA in SME Type 2 subjects led to improvement in motor function and achievement of motor milestones following treatment. Initial results of this study in pre-symptomatic SME newborns are also encouraging with subjects demonstrating improvement in CHOP INTEND scores. Additionally and recently our partner Audentes Therapeutics also announced new positive data for the treatment of X-linked myotubular myopathy from their Phase I/II clinical trial of AT132 at the American Society of Gene Therapy and Cell Therapy Meeting in Washington D.C. Audentes reported that significant and sustained improvements in neuromuscular and respiratory function in both dose cohorts were observed with corresponding achievement of clinically meaningful motor milestones. AT132 uses the NAV AAV8 vector. As licensee programs progress and achieve efficacy and safety milestones, we believe that they further validate the broad application of the NAV Technology platform and provide additional data that collectively drive the advancement of the AAV gene therapy space. Please refer to our press release issued earlier today for specific updates on all of our external partners. As our internal programs and the work of the NAV Technology licensees progress, we are enthusiastic about bringing the scientific advances and potential curative treatment options to those suffering from severe diseases.
And with that, I'd now like to turn the call over to Vit for a review of our financials.
Vittal K. Vasista, REGENXBIO Inc. - CFO [6]
Thank you, Maverick. REGENXBIO ended the quarter on March 31, 2019 with cash, cash equivalents and marketable securities totaling $444.3 million compared to $470.6 million as of December 31st, 2018. The decrease was primarily attributable to net cash flows used in operating activities of $29.3 million. Revenues were $900,000 for the 3 months ended March 31, 2019, compared to $132.4 million for the same period in 2018. The decrease was primarily attributable to $132.1 million of nonrecurring revenue recognized during the 3 months ended March 31 2018 under our amended license agreement with AveXis for the development and commercialization of treatments for SMA research and development expenses were $25.2 million for the 3 months ended March 31 2019, compared to $19.6 million for the same period in 2018. The increase was primarily attributable to personal cost as a result of increased headcount, laboratory and facilities costs and external expenses associated with conducting clinical trials and manufacturing-related services. General and administrative expenses were $11.6 million for the 3 months ended March 31, 2019, compared to $8.4 million for the same periods in 2018. The increase was primarily attributable to personnel cost as a result of increased headcount and professional fees for advisory and other services.
Net loss was $32.2 million, or $0.89 basic and diluted net loss per share for the 3 months ended March 31, 2019, compared to net income of $104.2 million or 3.30 and $3.04 diluted net income per share for the same period in 2018. As of March 31. 2019 we had 36.6 million common shares outstanding. Upon regulatory approval and product launch, Novartis's ZOLGENSMA is expected to provide REGENXBIO with its first revenue stream from royalties on commercial product sales adding commercial revenue to its existing base of licensing revenue this year.
Based on REGENXBIO's current operating plan and excluding any royalties from ZOLGENSMA, REGENXBIO reiterates that it expects its balance in cash, cash equivalents and marketable securities to be between 330 and $350 million as of December 31st, 2019, which will be used to support the continued development of its lead product candidate programs.
With that I will turn the call back to Maverick to provide final thoughts and review our upcoming 2019 milestones.
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [7]
To summarize what we've discussed today, as Iceman just described, we are expecting seeing the approval of ZOLGENSMA by Novartis, the FDA in the U.S. In addition, focusing on REGENX's internal programs, the interim Cohort 3 data from the Phase I/IIa trial for wet AMD provided evidence that onetime treatment RGX-314 can achieve long-lasting clinical effect reaching over 1 year with 50% of subjects treated with RGX-314 continuing to remain free of anti-VEGF injections.
Our expanded Phase I/IIa trial for RGX-314 is progressing as planned and is expected to complete enrollment in the first half of 2019. We plan to present top line data from that trial by the end of 2019 that will include new data from Cohort 4 and Cohort 5 and we're on track to initiate a Phase IIb trial for wet AMD in late 2019.
We announced today that we also plan to file a new IND for RGX-314 in the second half of this year for an additional Phase II clinical trial in diabetic retinopathy, a progressive retinal conditioning and leading cause of blindness and impaired vision in adults between 24 and 74 years of age. Diabetic retinopathy is a serious public health concern. Almost 30 million Americans have diabetes and nearly 8 million of them are estimated to have diabetic retinopathy. Dosing has begun in the first of 2 expected cohorts in the Phase I/II clinical trial for RGX-121 for the treatment of MPS II. We had a 28-week safety assessment where RGX-121 continues to be well tolerated with no SAEs reported and additional recruitment and site activation are ongoing. Recruitment and site activation also continue in the Phase I clinical trial of RGX-111 for the treatment MPS I. For RGX-501 for the treatment of HoFH patient screening is reinitiated for enrollment of subjects in Cohort 2 with corticosteroid prophylaxis.
Now we expect to present interim data updates for the RGX-121, 111 and 501 trials, all in the second half of 2019. And lastly for RGX-181 for the treatment of CLN2 disease, the IND enabling studies are progressing and we expect to file an IND or a foreign equivalent for the first in human clinical trial evaluating RGX-111 in the second half 2019.
At REGENXBIO we are committed to improving lives through the curative potential of gene therapy based on our proprietary NAV Technology Platform. Looking back at all that we've accomplished over the past 10 years, I'd like to take a moment again to recognize the excellent work by our employees, partners, clinical trial investigators and of course every individual and family who've chosen to participate in our clinical trials. With our innovative science, inspired people, partners, strong cash position, we're well positioned to achieve future milestones as we embark on the next decade in our drive to advance therapies for patients with significant unmet medical needs. And with that we'll end the call and turn it over for questions. Operator?
Questions and Answers
Operator [1]
(Operator Instructions) Matthew Harrison, Morgan Stanley.
Matthew Kelsey Harrison, Morgan Stanley, Research Division - Executive Director [2]
Thanks for taking the question and thanks for all the updates. I guess, first one for me, can you just comment briefly, you called out the protein levels at 1 year for both -- all the patients and then the patients that didn't have a VEGF injection. I guess the question would be sort of an 80 nanogram per milliliter difference between them or the levels have been trending sort of above 250 for the people that didn't get injections. Do you see that as a threshold effect or how would you interpret the levels in that group versus the levels in the overall group?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [3]
Matt, I'll start off and maybe ask Steve if he wants to jump in as well. I think, look we're encouraged that we're seeing consistency across the whole group and as well, consistently across the 3 that haven't received any injections which still for us is the purest form of evaluation based on the assay method that we're using and the potential for interference. Although I think what we're most encouraged by is that we continue to see those related correlations to the BCVA and CRT related to protein expression. And I think where -- the hypothesis of this program from the outset has been that using AAV gene therapy to achieve durable sustained protein levels was going to have the best effect on the disease. We're seeing that at Cohort 3 now at 1 year. Steve, I don't know if you have anything to add.
Steve Pakola, [4]
Sure. Thanks for the question, Matthew. Yes, I think it's important to remember also take a step back and realize these are aqueous humor concentration. So it's already a proxy for what you're getting produced in the retina. So I don't think it's kind of a thing that you can put a fine point on exactly what threshold is going to be relevant. So really as Ken has mentioned what we look at here is the consistency over time in these patients where whether you look at the 3 subjects or the 6 subjects whichever and you look at, we see sustained protein expression.
Matthew Kelsey Harrison, Morgan Stanley, Research Division - Executive Director [5]
Okay, thanks. That's helpful. And then -- and my second question is just on the MPS I and II programs, it sounds like recruitment has been slow in those programs. But you've committed to some sort of update in the second half. Can you just help frame for us what kind of information you think we should reasonably expect in the second half?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [6]
Yes, Matt, I mean we obviously checked in on the 121 program in terms of the safety assessment that occurred at 20 weeks and the protocol has us collecting samples throughout the trial, including CSF, serum for additional evaluation of biomarkers and protocol also allows for evaluation of other clinical measures. So I think we've said from the outset when we started off this year we're going to collect as much data as we can based on the pace of enrollment throughout the year. I certainly would expect that we're going to have aspects of a broader safety story as well as the emergence of some of those initial clinical biomarkers and other clinical evaluations by the end of 2019 in both trials.
Operator [7]
Gena Wang, Barclays.
Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [8]
Thank you. My first question is regarding wet AMD program. For the Cohort 3, the [rescue] injection. The injection should be 4.6 based on our calculation. How is that compared to the 2 cohorts at the lower doses? I think the reason I am asking is, did you see any protein dependent response in terms of the rescue injection?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [9]
Yes. So we updated this on corporate deck today Gena and I think we reported that in Cohort 1 patients were receiving on average of over 10 injections for a year and in Cohort 2 close to 9 injections. So there is even a noticeable difference, I think, obviously between Cohort 1 and Cohort 2 and what we're seeing across the whole body of Cohort 3.
Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [10]
Okay, great. And also I think the protein level seems that there is some slight decline compared to the six months? Is there any concern or do you think that that's just within the normal experimental error?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [11]
Yes, I think you've hit on it there, Gena. We're seeing things that we think are a function of what we know about this assay method and its overall accuracy and our interpretation. And I think informed by even how sort of FDA guidances would interpret assay results like this is that we're seeing a substantially equivalent results here, based [on the ECL] assays.
Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [12]
Okay. And regarding diabetic retinopathy, what would be the dose for this indication?
Steve Pakola, [13]
Hi, Gena. Steve here. So that's to be determined. One of the nice things is we have the ongoing wet AMD study and data is still to come from Cohorts 4 and 5 where we're going to learn a lot from those. So both in confirming the safety and tolerability as well as seeing effect. One of the nice things about DR in general, as we know that it is a highly VEGF driven disease, whether at the stage of diabetic retinopathy or the actual complications such as DME and PVR. So we can learn from also the pharmacodynamic response that we see in the ongoing study. So that will inform before finalization of the protocol for the DR Phase I -- the Phase II study.
Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [14]
Okay. Well, will you be thinking one dose or potentially 3 will be 2 doses?
Steve Pakola, [15]
I think it's likely we consider 2 doses, more than 1 dose. But again -- a final decision is really going to depend on what we see going forward.
Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [16]
Okay, great. And my last question is regarding the IP for AAV9 indication in SMA given the approval will happen anytime soon? So what would be your plan for extension for both Europe and U.S.? And also will this apply to both IV and intracisternal administration?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [17]
Right. So the AAV9 IP that was originally licensed to AveXis back in 2014. Covered the use of AAV9 for the treatment of all forms of SMA, including all routes of administration, basically sort of parent patent that focused on gene transfer with AAV9. That was very novel and non-obvious at the time of the discovery. So all of the work that is covered under the ZOLGENSMA program relates to that field that was licensed. And we've also of course when we amended the agreement with AveXis in early 2018, included additional intellectual property that related to the program and future development opportunities that AveXis know Novartis will have. As we've talked about before and I think with you and others, Gena, the plan for how we will work to approach patent term extension in the U.S. and Europe is kind of known processes and we're going to be talking to the sponsor, which is now AveXis subsidiary Novartis about working together to initiate certain applications where needed. In other cases, it's going to be our responsibility as REGENX to affect certain applications that need to go in in different jurisdictions. And as you alluded to the trigger point here is going to be in all cases, the actual licensure of ZOLGENSMA which we're anticipating this month, at least in the U.S.
Operator [18]
Mani Foroohar, SVB Leerink.
Mani Foroohar, SVB Leerink LLC, Research Division - MD of Genetic Medicines & Senior Research Analyst [19]
Hey, guys. I got 2 quick questions. As I'm looking at the protein levels that just goes in the press release, across Cohort 3 we are looking at a 180 nanograms per ml and we've got 260 per ml in the 3 anti-VEGF injection free patients. That implies about 100 per ml for the remaining 3 patients. Have you disclosed or do you plan to disclose the protein level curve for those patients as you have here, one month, six months, 1 year or do you think that that's not really useful data and it's not really interpretable?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [20]
So, we have disclosed one -- well, you mentioned that we've disclosed the 180 at 12 months and six than we had disclosed, the one month and the six-month, Mani. So it's all available at this point.
Mani Foroohar, SVB Leerink LLC, Research Division - MD of Genetic Medicines & Senior Research Analyst [21]
Okay. Right. That's helpful. And the other question that I have, when you think about moving forward into a pivotal study, the study that you've RGX-314 thus far evolved and demonstrated anti-VEGF responders with multiple years of therapy. Do you expect that it will be -- that a pivotal study head to head versus an approved product would also be exclusively in anti-VEGF responders or will there be some anti-VEGF-naive patients there?
Steve Pakola, [22]
As we look at it now, I think going forward we obviously want patients who are anti-VEGF responders. We will give more details on our forward-looking clinical development plan in the second half of this year.
Operator [23]
Ying Huang, Bank of America Merrill Lynch.
Josh Schimmer, Evercore.
Joshua Elliott Schimmer, Evercore ISI Institutional Equities, Research Division - Senior MD & Equity Analyst [24]
[If I run] some really simple back of the envelope math, the cohort of -- the patients in Cohort 3 were not VEGF injection free. And then I adjust the protein expression levels in those patients and think about Cohort 4, I would have expected that all those Cohort 4 patients since their doses is so much higher than Cohort 3 will now be in this 250 type band to be anti-VEGF injection free in the follow-up. And yet you then went to Cohort 5. So is there -- is the math wrong to say that Cohort 4 should have had all patients now with adequate protein levels to avoid further anti-VEGF injections or is that not the case?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [25]
Hey, Josh. Thanks a lot. Thoughtful question as usual. I think first -- the primary driver for addressing moving to Cohort 5 was really end of your discussions at 2018 with FDA about wanting to think about how we would broaden and deepen the 314 program including, like the example today moving into diabetic retinopathy. And I think we established that building the most complete safety database from the Phase I now I/II2a study was the best possible platform to do that to provide us multiple absolute flexibility on a going forward basis. And I think the fact that we will not have to run any additional preclinical studies, the fact that we will leverage the safety data and leverage dose selection from the Phase I/IIa moving directly into DR is an example of that. Otherwise, yeah, look in theory, I think we believe that more protein is going to show more response. And I think that's been the case in what we've seen with Cohorts 1,2, 3 and I think it's what we're looking to explore and even by increasing the size of the cohorts with Cohort 4 and Cohort 5. What we also know is that wet AMD in particular is a heterogeneous disease. And we also want to make some assessments of how we will power programs going forward in order to be able to establish best possible outcomes with what we already are seeing as emerging is encouraging data with respect to clinical response to a durable levels of protein. Steve, I don't know if you want to add anything.
Steve Pakola, [26]
No. [That works.]
Mani Foroohar, SVB Leerink LLC, Research Division - MD of Genetic Medicines & Senior Research Analyst [27]
Do you envision different doses then for diabetic retinopathy versus wet AMD?
Steve Pakola, [28]
Well, again, we'll have to see what we find here. I think there is comfort in all the data that exists with various anti-VEGF programs where we can look at the pharmacodynamic response of different anti-VEGF programs in both different DR and DME indications and also wet AMD. That gives us some comfort in terms of potential range of doses where we might expect certain PK findings to translate into the intended pharmacodynamic effect in DR. But again, we're going to have to see the results that we get from the wet AMD study.
Mani Foroohar, SVB Leerink LLC, Research Division - MD of Genetic Medicines & Senior Research Analyst [29]
Maybe last question, is there any clinical features or predictors of which patients may have higher versus lower protein expression levels within each cohort?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [30]
Well, I think it's important to note, these are small sample sizes. So there is a limit to how much you can read the tea leaves so to speak in terms of what variables might be related or not related to PK or PD for that matter.
Steve Pakola, [31]
I think we're happy to have this protein data as another place to sort of anchor ourselves into what's happening scientifically as well as clinically and I think we're also encouraged by the fact that we're running this study at multiple sites and sort of as we've talked about in the past wanting to think about all the variables that go into a successful product for a one-time subretinal initiation of treatment. It was about measuring protein, it was about getting early data on sort of different surgical centers and their ability to do this and to scale like we talked about at the investor meeting, and now we're collecting the clinical data as well. So we're excited about where this is at this point, encouraged by what we're seeing. Second half of the year going to be a lot of decisions to be made.
Operator [32]
(Operator Instructions) Ying Huang, Bank of America Merrill Lynch.
Unidentified Analyst, [33]
Hi, good afternoon. This is [Chen] on behalf of Ying. Sorry there were some technical difficulties. I have a couple of questions. The first one is like when I was doing the calculation, right, the Cohorts 3, with the rescue you received average of 4.6 injections. But if we do the calculation on the BCVAs, almost like a zero. So I wonder what are you thinking about -- like what criterias are you actually thinking about when doing the rescue. And also want to confirm that the patients Cohorts 3 without the rescue, are they all dry in their eyes?
Steve Pakola, [34]
Well, on the question of rescue. We have actually pretty strict rescue criteria here. So we're not letting patients go. And certainly relative to precedent of other trials that are out there these patients are getting treated if there is a decrease in visual acuity of 5 letters associated with fluid or if there is an increase in fluid or ocular hemorrhage. And that constellation of criteria is actually stricter than some of the other concurrent studies that are out there.
Unidentified Analyst, [35]
Okay. And a follow-up on the patients without rescue. So if you compare 12 months you have average increase of 10 letters versus 13 in 9 months. I wonder whether that's just like variability or you think that is a trend going down in all the 3 patients?
Steve Pakola, [36]
Yeah, I think especially with BCVA if you're talking about a magnitude of 3 letters or 4 letters, that's certainly within random variation that you would expect in a -- at different time points in a trial.
Unidentified Analyst, [37]
Okay. And the next one is that, do you think there is a possibility to retreat patient who are not achieving sufficient protein levels at this point? Is there something in the plan?
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [38]
I think we need [to alleviate] here for that. Chen that's something that I think all of us in gene therapy are interested in exploring scientifically at different levels, but it is not currently part of any clinical plan or design in terms of advancement of 314 in the near term.
Operator [39]
Thank you. And we're showing no further questions at this time. I'd like to turn the call back to Mr. Ken Mills for closing remarks.
Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [40]
Thank you, operator. I just wanted to point out to everyone who are listening on the call that we did provide some updates of the data also in our corporate deck that can be found on the website, including some of the longitudinal data on the subjects from Cohort 3 in more detail. So, thanks everyone for joining us today. We look forward to providing with further updates. We're really encouraged by what we're seeing this past quarter in terms of the success in execution on clinical development, both at REGENEX and through our partners. Have a great night.
Operator [41]
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone have a great day.


text:
Hi, my name is Jackie and I am a happily married mother of two handsome boys. I am a primary school teacher, but currently I have the amazing and very busy job of being a full time stay at home mum. My husband and I are very interested and involved in house renovations and rental properties. When I have the time, I enjoy reading, gardening, walking and sewing. I also love writing and am very excited to be an author here on inscribd.com
On this page your will find over 100 quotes and sayings that will touch upon strength, courage, confidence, success, happiness, money, goals, hard times, following your dreams, achievement, overcoming adversity, self esteem, positive thinking, fear of failure, hard work, meaning of life, purpose, passion, determination, discipline, focus, self empowerment, greatness, and more!

subset: commoncrawl


text:
Gonorrhea is a nasty STI that can lead to many complications, down the line, and we're losing the battle in treating it.
Dating and not using condoms? The World Health Organization (WHO) has issued a recent friendly reminder to humanity that cases of gonorrhea are on the rise, and we don't really have drugs to treat them all.
Well, we do but Big G has successfully become resistant to so many antibiotics so far, that doctors and scientists are down to the last line of drugs, when it comes to treating the illness.
Related: 5 Questions Your Gynecologist Would Love to Answer
And even those don't always work. According to BBC.com, 3 recent cases of gonorrhea have been completely untreatable- one in Japan, one in Spain, and a final case in France. Those involved in these cases will have the illness forever. It can cause infertility in both men and women, extreme pain in the pelvic area, pelvic inflammatory disease (PID), and inflammation of the brain or spinal cord. A scary future.
The problem is, many people contract gonorrhea and display no symptoms, or simply very mild ones. These can include thick green or yellow discharge for your vagina or penis, pain when peeing and bleeding, for women, between periods. In fact, having no symptoms is so common that over three quarters of gay men, and women (gay and straight), have no easily recognizable symptoms at all, when infected.
What can you do about it? Wear a condom. Even if it's simply oral sex.
Photo credit: Kaspars Grinvalds/Bigstock


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- Description
At a Glance
This award-winning three-position design holds your baby in an ergonomic, natural sitting position. The padded waist belt ensures babys weight is evenly distributed between your hips and shoulders for long-wearing comfort while the adjustable, extra-padded shoulder straps provide you with ultimate comfort. In any colour or print, the Ergobaby original carrier is the perfect choice as you embark on wonderful adventures with your little one.Features and Benefits
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- lumbar support waistbelt from 66cm - 140 cm, with double adjusters for easy tightening, can be worn low or high on waist to maximise comfort for your lower back or post C-section
- cushioned, extra-padded shoulder straps ranging from 72.2-121.2 cm
- large zippered storage pocket
- adjustable hood to protect baby from the sun and offer privacy 100% Premium Cotton
- acknowledged as a hip healthy product by the International Hip Dysplasia Institute
- machine washableDon't forget
To take a look at the full Ergobaby range on our website. Check it out!What's in the box
x1 carrierWant to know more:
The Ergobaby baby original carrier allows you to carry your little one in three positions, front-inward, hip and back from baby to toddler. Designed with a deep seat for a spread squat, natural M seating positionto help support their developing spine and hips whilst they are being carried, and are supported in the carrier using the Infant Insert which is available separately. The adjustable hood protects your baby from the sun and offers privacy too. For older babies, the Ergobaby carrier can also be used to carry your baby on your back, or hip.
The Ergobaby baby carrier now features an adjustable lumbar support waistbelt which can be worn low or high on waist to maximise comfort for your lower back or post C-section and cushioned, extra-padded shoulder straps for long-wearing comfort, It has been designed to ensure that the weight of the carrier is evenly distributed across your hips and shoulders to ensure there is no strain on your back. The Ergobaby carrier also features a handy zip pocket allowing you to securely store your phone, keys or purse securely and in a easy to reach place.Care instructions:
Machine washableVideo:
- Customer Reviews
- Delivery & Returns
Standard Delivery
We will deliver all stocked items within 3-5 working days. Courier costs as stated at the check-out, generally $5.90 for orders below $60, and free for orders $60 and above. We deliver anywhere in Singapore, with the exception of offshore islands and restricted zones.
If you ordered a cot that requires assembly, or if your order exceeds $500, it will be taken care of by our Mothercare in-house fleet. Our delivery team will SMS to arrange a date and time that you are available.
Express Delivery
We currently do not offer express delivery. If you need express delivery for special circumstances please email us at email@example.com. Not valid for delivery requiring assembly.
Click here for the full delivery information and here for our return & exchange policy.
- Specifications
Colour Grey Care instructions Machine washable Product Weight 0.79 kg Product Height 45.72 cm Fabric Composition 100% cotton Washable Machine washable Age Range From 6 months Age Range To 3 years Minimum Weight 5.5 kg Maximum Weight 15 kg Baby Carrier Lower Back Support Yes No. of Carrying Positions 3 Video View video Style 57557


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Peter D Neptune
November 20, 2009 – guardian.co.tt
She said that in total, from January 2007 to the end of March 2009, the state borrowed more than $8.8 billion. This includes nearly $3 billion from the domestic capital markets and more than $5.8 billion from international sources. Prior to the current fiscal period, the Central government borrowed three times through bond issues on February 2007 amounting to $674.3 million, in April 2007 another issue was made for $1.02 billion, and this was followed up by another bond issue of $1.2 billion in February 2008. The Minister said all three approaches on the local market was necessary for liquidity management and to control inflation in pursuit of the government's management strategy for the local economy. External borrowings included 190 million British pounds (TT$2.008 billion), US$465 million (TT$2.953 billion), 17 million Australian dollars (TT$99 million) and Chinese RMB 800 million (TT$744 million). The total external borrowings in local currency from January 2007 to March 2009 was valued at TT$5.8 billion.
The external loans include 190 million British pounds as export credit guarantee for the purchase of two fast support and intervention vessels, three offshore patrol vessels as well as training and support packages for the purchase in April 2007.
Also in April 2007, government borrowed US$15 million and 17 million Australian dollars to purchase another six fast patrol crafts. Thirteen months later Government again approached the international markets in May 2008, to refinanced a US$150 million bond issue that was due for repayment. This was followed up one month later in June 2008, when government secured a Buyers Credit Loan for the construction of the Alutrint aluminium complex project. At that time another Chinese RMB 800 million loan was secured through a concessional rate facility with the Chinese government for the construction of Alutrint. Minister Tesheira said the interest rate on the funding ranged from a high of 8.25 per cent for domestic borrowings, to as low as 2 percent for the Chinese loan for Alutrint.


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Aesthetic ineffability
In this paper I argue that recent attempts at explaining aesthetic ineffability have been unsuccessful. Either they misrepresent what aesthetic ineffability consists in, or they leave important aspects of it unexplained. I then show how a more satisfying account might be developed, once a distinction is made between two kinds of awareness.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics
Document Type: Research Article
Affiliations: Centre for Logic, Institute of Philosophy, Kard. Mercierplein 2, 3000 Leuven, Belgium.
Publication date: August 1, 2000


text:
Disclosure: We were sent the featured products for the purpose of this post however all opinions are my own.
Any reader will know how much we love Frugi and so when they announced their new swimwear range we were more than a little excited. With our first family holiday abroad approaching so quickly LP couldn't wait to choose a new swimming costume and we spent quite a while looking at the great designs – typical swimsuits and those all in one suits with arms and legs, great for keeping children protected from the sun.
LP chose the Little Sally Swimsuit and couldn't wait for it to arrive. Luckily for us, as soon as it came through the door the weather was nicer than it had been all year and so she put it on to play with the sand and water table in the garden, making the most of the afternoon sun.
I often find with girl's swimwear that it can be too skimpy, low cut at the top, high legs at the bottom and really just too revealing for a small child. I loved the Little Sally Swimsuit immediately. It covers LP up but lets her feel girly – it's a swimsuit perfect for her age.
LP loves the daisy design and I love that she can wear something bold and beautiful that she loves and isn't pink – her current obsession. The swimsuit is Oeko-Tex and UPF 50+ giving us peace of mind that she'll be safe in the sun – we just need to keep her arms, legs and face topped up with cream.
LP is a very petite four and a half year old and so the Little Sally swimsuit in age 3-4 was a good fit for her with room to grow. Frugi sizes are generous and the material is such great quality that their products last for years. I love that now the children can wear Frugi for any time in the lives – even when they're swimming. To check out more of the Frugi swimwear range make sure you visit My Two Mums for the next Frugi Family review.
The Frugi Little Sally Swimsuit has an RRP of £16.00


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The newly elected student union president, the person of "Reedof has beseech and made known to the school authority about the general tablet which has being made compulsory for every fresher in the University of ilorin.
I am sure he felt the pain of those student who had to defer their admission due to the fact that they couldn't pay for the tablet, this is one of the most interesting step he has taken.
I stand with the one who makes the right decision.
I stand with reedof.
_About the issue of the PC tablets_
It is 90% done now,that the incoming fresh students will not be collecting PC tablet
Pc tablet is about to be scraped bcos it's not serving it's purpose,the SU in conjunction with the senates decides
*SU president*
Then in my own point of view, if PC tablet is being scraped, what should happen to bandwidth? will the school authority consider the number of unilorites who are using browsing phones, the one who are staying in school? If we are to consider how many people uses the Wi-Fi which is being produced by the school then We will realize there is a need for the school authority to either reduce the price or scrap it out.
Some faculty issues password which makes it difficult for most student to have access to the Wi-Fi which has being paid for by them.
I hope this issue is also being addressed as our able student union president stand in for the student at large… I stand with reedof


text:
|Map4Parenting Book
Get your copy today!
Hardcover Book
At Choose Life Church
12 March 2019 @ 19:00
Discipline Puzzle Picture Revealed
Finding discipline a puzzle that you are battling to solve?
We will reveal a Discipline Puzzle Picture Box to you that will equip you to implement a sequential discipline strategy, enabling you to be a more effective parent.
10 September 2019 @ 19:00
Empower your Child against Bullying
Teach your child to be tease proof. Teach them how to be assertive.
Teach them to stand up for themselves in a kind, firm way lessening the chances of being targeted in the future.


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Frank Stella's studios, early and late
MA: How did it start from a small studio on East Broadway to this? This studio is literally approximately one square acre enclosed.
FS: . . .It's a fairly natural evolution if you keep on working.
Michael Auping and Frank Stella in conversation, Tuesday Evenings at the Modern, April 12, 2016
Michael Auping began his conversation with Frank Stella in the present, with an image of the artist's current studio in Newberg, New York, then moved the conversation to the artist's historical early work.
Watching the eighty-year-old Stella in front of a packed house and below large projections of his work, it was clear that the artist is secure in his choices for his life and career, and it seems that he always has been. There is a playful banter between the two men who have been working on the exhibition Frank Stella: A Retrospective for an extended period of time and surely know what to expect from each other in a public conversation. Nevertheless, the conversation was fresh, and Stella let nothing slide—and for the sake of the audience, Auping left some disagreements unchallenged while pushing on others. Stella's thoughtful and determined responses to Auping's carefully considered questions and observations was a reminder of the incredible confidence he exuded as a young artist who boldly stated in a 1964 interview, "What you see is what you see"—a proclamation credited with changing the direction of art, or at the very least bringing into supreme focus the direction art was moving.
Despite what appear to be radical shifts in Stella's work from series to series over the last sixty years, it seems that his early conviction, "what you see is what you see," still rings true. Perhaps at the core, not that much has changed from the Black Paintings to the most recent work—a revelation that has me reconsidering each series and each piece within. It was a real pleasure to hear from someone of Stella's experience, whose ideas took root in the beginning of what has been remarkable career.


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Gets or sets the active dock item.
This is a dependency property.
public BaseLayoutItem ActiveDockItem { get; set; }
Public Property ActiveDockItem As BaseLayoutItem
An active dock item is the item that has been clicked or contains a focused control.
Before a dock item is activated, the DockItemActivating event fires. It allows you to prevent item activation. The notification DockItemActivated event fires after the item has been activated.


text:
You've waited months-maybe even years-for your special day. When you enter your reception hall, everything should look exactly as you wanted. You shouldn't have to compromise on your event design to create a look that fits your budget. Exquisite & Elegant Designs can design the wedding you've always imagined without making you sacrifice your style preferences.
Call 254-466-0116 today to speak with one of our experienced wedding designers about our event planning & event design services. We're always happy to answer your questions.
Exquisite & Elegant Designs in Killeen, TX can work with budgets and events of all sizes. In addition to weddings, you can count on our team to plan you or your loved one's:


text:
Kanye West a piece of work. He took the time to diss Ray J , Reggie Bush and some other dudes that used to date Kim Kardashian. I don't know who he was talking to exactly. The crazy thing was the declaration was made at the BET Honors show that took place last night. Kanye is interesting to say the least.
That new song is yok though. Sorry. #factsonly
If the video doesn't load, click here.
This might be a stretch, but who cares.


text:
Problem solving Facebook application where users choose a panel of peers to solve their problems and may keep their identity private.
- Stage Full Product Ready
- Industry Software
- Location Fortuna, CA, USA
- Currency USD
- Founded January 2010
- Employees 4
- Website esolveit.com
Company Summary
Problem: Social networking has no purpose, privacy or responsibility Solution: esolveit, provides users with all three. The purpose is people helping people one solution at a time. The privacy is users are allowed to remain anonymous. The responsibility factor is the site is meant to help users deal with they're problems in a safe anonymous environment. Market: 650 million social network users already use question and answer sites.
Denise Del MonteCEO
Denise Del Monte
November - 2010 Founder and CEO of esolveit .com INC.
2006 –Present Founder and CEO Apex Real estate INC. Apex Real Estate Inc. is a real estate brokerage and property management company for the public. Apex sells residential and commercial real estate for the greater Humboldt county area. Apex has a mixed residential and commercial property management division.
1999 – Present CEO Del Monte Properties and In
Sarmad AbbasDevelopment Team
Project Manager
Avenue Social Inc.
Client communication during various phases of project till its completion and gathering project details
Drafting technical documents after requirement gathering, outlining system functionalities and processes for the development team
Assigning tasks to team members on daily basis and assisting the team by providing UAT Cases during the finalization of project.
Business Analyst
Salsoft Technologies
Ruskow Green and tanLawyerUnconfirmedBarry KayeAccountantUnconfirmed
Previous Investors
Mike and Serene De CorraUnconfirmed


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What changes in 2019 regarding French taxes and social charges on income, investments and assurance-vie, and how will the new PAYE system affect you?
Anyone who has been living in France a while knows how frequently tax rules can change, and how significantly too. In the last 10 years we have seen wealth tax reformed to make it less of a burden, then that reform reversed, then a complete overhaul to create a new tax. We lost a fixed rate of tax on investment income, then a few years later a new one was introduced…
All this can create headaches for effective tax planning. You need to carry out regular reviews to make sure your tax planning is up to date and you are taking advantage of the tax mitigation opportunities the French tax regime has to offer.
2019 budget
A new President usually means tax reforms, and we had that with the 2018 finance bill. The 2019 budget, however, is one of those rare occasions where very little changes. The one big change in 2019 is the introduction of a pay-as-you-earn (PAYE) system in France (see below), but that was part of the previous budget.
On the other hand, the Social Security budget for 2019 did introduce significant and potentially beneficial changes.
Income tax
There are no changes to income tax rates, though the bands have increased very slightly with inflation. The 0% rate will cover income up to €9,964 and the highest 45% rate income over €156,244. This is for your 2019 tax return, so income received in 2018.
Investment income
2018 saw the introduction of the Prélèvement Forfaitaire Unique, or 'flat tax' as it is commonly known. This applies to interest, dividends and capital gains on the sale of shares and securities. It does not apply to rental income.
The rate is 30%, which includes income tax and social charges, and it remains unchanged for 2019.
Lower income households can opt to use the scale rates of income tax instead (plus social charges), though that this would have to apply to all your income.
There are no changes to assurance-vie this year (though some policies will benefit from the social charges reform, see below). This is great news for savers and investors who are looking for an arrangement that provides both tax-efficient income and estate planning advantages.
The 30% flat tax applies to policies set up after 26th September 2017. If you have an older one you can choose whether to pay income tax at the progressive rates or the previous flat tax system, whichever is more beneficial. In both cases social charges are paid in addition.
The allowance for policies held for more than eight years stays in place for all policies (€4,600 for individuals and €9,200 for married/PACS couples).
Social charges
The main social charges rates remain the same as last year:
However, those whose pension income is less than €2,000 per month (or €3,000 for a couple) now pay a lower rate of 7.4% on this income. As always, if you hold Form S1 or are not part of the French health care system you do not have to pay social charges on pension income.
The second key reform introduced by the Social Security budget for 2019 income is that, if you covered by the health system of another EU/EEA country – so if you hold Form S1 or are non-resident – you no longer have to pay the full 17.2% social charges on investment income and capital gains, and instead now pay a new lower flat rate of 7.5%. This is very good news for those affected.
Read more about social charges in 2019
Wealth tax
2018 also heralded a big reform for wealth tax. Instead of covering most of your worldwide assets, it now only applies to real estate assets. Savings and investments (including assurance-vie policies) are no longer subject to this tax.
Again, there are no changes for 2019. The current threshold of €1,300,000 remains in place. Tax rates start at 0.5% for assets between €800,000 and €1,300,000, rising progressively to 1.5% for assets over €10,000,000.
This may change next year. Following the December unrests in France, including the Gilets Jaunes (yellow jackets) demonstrations, a committee has been set up to review whether the old-style wealth tax should be re-introduced from 2020.
The 2018 reform put property at a significant disadvantage to capital investments, particularly when you consider that rental income does not benefit from the 30% flat tax either. If you are wondering where to invest, weigh up the tax considerations carefully. If you already own more than one property, it may be worth downsizing your property portfolio.
Succession tax
The succession tax regime remains unchanged this year. If you have not reviewed your estate planning for a while, though, it is always worth doing so to ensure you are taking advantage of all the opportunities to lower this tax for your family and heirs – particularly where heirs will face the higher tax rates.
PAYE finally comes to France
After being in the pipeline for a number of years, the new PAYE system start in 2019. So from 1st January, French tax residents will be subject to a monthly withholding tax on their income.
Note, however, that the French system is different from what you may be used to, for example in the UK. The amount of PAYE deducted each month in 2019 will be calculated on your 2017 income, as declared in May 2018. Any balance of tax must be settled by the end of year.
Income subject to PAYE applies to (but is not limited to):
Investment income - interest, dividends, capital gains and gains from life insurance policies/non-French assurance-vie – is excluded from PAYE. It also does not apply to non-French income that receives a tax credit in France under a double tax treaty (eg, UK rental income earned by a French resident).
For French source income, monthly PAYE will be collected by the paying agent. For all your other income, you will need to set up monthly or quarterly direct debits to pay it yourself.
No-one ever said French tax was easy. Last year's reforms were very welcome, and many people who have savings and investments will see a difference in their tax bills this year. This year's reduced social charges, for those eligible, will also help. But this does not lessen the need for a good understanding of the complex regime and considered tax planning. With different assets being taxed quite differently now, it is worth taking a step back and asking your local Blevins Franks tax and wealth management adviser to review your investment assets. We will make sure your tax planning arrangements are up to date and specifically structured around your family situation and your objectives.
Contact us for a tax and wealth management review
The tax rates, scope and reliefs may change. Any statements concerning taxation are based upon our understanding of current taxation laws and practices which are subject to change. Tax information has been summarised; an individual is advised to seek personalised advice.


text:
Dr. Kate Behr
Chair of English, Professor of English, Director of Fellows Program
Professor Kate Behr has been the English professor at Concordia since 2000, teaching all parts of the curriculum. She came to New York from the UK in 1995. Before joining the Concordia faculty, she held full-time positions at Iona College, NY; Exeter University, UK; and Pembroke College, Oxford. She is also a sessional Professor of Literature at St Vladimir's Orthodox Theology Seminary, NY.
D.Phil. English Language and Literature, Pembroke College, University of Oxford, UK;Bachelor of Arts, English/Drama/Theatre-Studies, Royal Holloway College, University of London, UK


text:
Greenebaum Donates Over $90,000 of Computer Equipment to Hanover College
LOUISVILLE, KY: Greenebaum Doll & McDonald PLLC is pleased to announce that the firm has donated over 325 computers and related equipment, an estimated value of $91,900.00, to Hanover College. Gently used desktop and laptop computers, along with docking stations, mice and keyboards were donated to Hanover after the firm recently upgraded its computer equipment.
This donation will replace or supplement Hanover's current computer inventory and allows the College to expand computer accessibility for students, faculty and staff. In turn, Hanover will donate surplus equipment to charitable organizations in need such as Girls Inc. of Jefferson County, Indiana; Goodwill BridgePoint Services Inc.; and Pathways Youth Shelter & Family Services.
"In this economy, many schools and nonprofits that rely heavily on government funding and donations are cutting back on technology expenses in order to balance their budgets. Because of this generous donation to our campus, we will be able to donate our surplus computers to needy organizations and put technology within reach to hundreds of others in our community," states John Collins, Chief Technology Officer and Associate Professor of Computer Science at Hanover College. President Sue DeWine added that "This kind of corporate support for higher education benefits everyone. We are especially pleased that we will be able to allow non-profits to benefit from this gift."
Phillip D. Scott, Chairman of Greenebaum Doll & McDonald, is a 1964 graduate of Hanover and currently serves as Chairman of their Board of Trustees. "Hanover afforded me many great opportunities during my college years and I'm thrilled Greenebaum is in a position to give back to such a fine school. Greenebaum takes pleasure in giving back to the community and we are happy to see the trickle-down effect our donation has created."
Hanover College is a premier, private, liberal arts institution located 45 minutes outside of Louisville in historic Madison, Indiana. Hanover's curriculum offers an interdisciplinary approach to over 30 majors with core strengths in the sciences, education and business. Hanover is continually ranked among the top schools in the U.S. for academic quality. Both U.S. News & World Report and The Princeton Review list Hanover as one of the top 40 "best values" in the nation. For more information, visit www.hanover.edu.
About Greenebaum Doll & McDonald PLLC
Greenebaum Doll & McDonald PLLC is a widely respected business law firm with approximately 150 professionals in five offices, serving local, national and international clients in virtually every industry. For more information, visit www.greenebaum.com.


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|"Premeditation" 8"x10" oil and acrylic on board
Monday, October 27, 2014
Carly Janine Mazur - M A S K S
2 comments:
- AnonymousOctober 28, 2014 at 1:58 PM
You seem to be having an excellent month.ReplyDelete
I'm finding that each week seems to add cohesion and strength to the previous ones.
Thanks Lee! It's been a really transformative month for me. It's all very exciting :DReplyDelete
Subscribe to: Post Comments (Atom)


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The Ribbon Syndicate League
Discussion in 'Pokémon Leagues' started by WhyBuffet, Nov 3, 2015.
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I guess you could call this politics as usual in Florida. The saddest part is not one of corruption as usual in the state of Florida but the fact that the non-profit gave '…In this latest case, some of the GOP lawmakers who are disgruntled with Scott have their own worries. Investigators say that Allied Veterans donated about $2 million to state and local political campaigns, and spent $740,000 lobbying in Tallahassee…' which most likely is more than they gave the vets who purportedly the non-profit was dedicated to serving. The the story because Carl Hiaasen is truly a great writer.
FL's lieutenant governor, in sham job, resigns in wake of Internet gambling sting


text:
Security Lights with Motion Sensor
STANDARD's Security LED lights help to ensure all areas are well lit and provide added security at night. They are equipped with a motion sensor, allowing lights to turn on automatically when movement is detected.
Lighting Applications
- Pathway
- Shed
- Back yard
- Docks
- Patio
- Parking area
- Building perimeter
Key features
- Life (L70) 50,000 hrs
- Watt 24 W
- Volt 120V-277V
- Colour temperature 3 000 and 4 000 K
- Housing colour bronze and white
- Installation options wall mount
- Operating temperature - 40 °C / - 40 °F to 40 °C / 104 °F
- ENERGY STAR certified (4 000 K only)
- Accessories mounting screws and motion sensor
- Adjustable heads – allow light to be focused where needed
- Maximum Range Detection 20 meters (65 feet)
- IP65 rating
- The motion sensor provides 180 degree detection
- Adjustable time settings up to 9 min
These security lights are equipped with a motion sensor as well as an integrated photocell that allow you to power the lights to turn ON when motion is detected during the day or at night. This system creates an inviting atmosphere and provides added security at all times.
These lights can also easily replace traditional luminaires while offering superior performance and savings on energy consumption. Indeed, the motion-activated built-in sensor turns light on when you need it, whereas traditionally, most lights stay on all night. This LED system eliminates waste and allows savings on energy consumption.
The LED Security Lights with a motion sensor are the perfect solution for areas that need to be well lit during the night, in areas where activity and foot traffic are irregular, such as yards, walkways, driveways, patios, parking lots and loading docks.


text: IMPORTANT! ComicbookDB.com will be closing its doors on December 16th, 2019 as we look towards creating a new and improved tool for collectors to utilize. We want to make sure everyone has a chance to download their data & collections by clicking on this link after logging in. Thank you to everyone who has taken the time to contribute to the site and we look forward to seeing you again soon. If you have any questions, click here. Action Comics (1938) #744 - Comic Book DB Free Services! Add New Content | Top Issues | Register | Marketplace | Forums | Request a Feature | Help | Mobile | Home Login Username: Password: Register for free Social Media: Search: Entire Site Title Creator Character Member Group Issue Name Story Arc Story Name Search by Cover Date Browse: Titles Creators Characters Groups Story Arcs Publishers Imprints TPBs/HCs Podcasts Awards Members Contributors Public Collections Public User Lists Last 10 titles added: 1. Symbiote Spider-Man: Ali... 2. Spider-Man 2099 (2020) 3. Doom 2099 (2020) 4. Annihilation - Scourge: ... 5. Annihilation - Scourge: ... 6. Unsmooth (2019) 7. The Crow: Hark the Heral... 8. Moomin: The Deluxe Lars ... 9. Witchfinder Omnibus (201... 10. The Complete Gail Simone... View All Last 10 creators added: 1. Andrea Di Vito 2. Everett 'E.S.' Glenn 3. Reuse@ 4. Ed Hipkiss 5. Winston Chan 6. Fei Chen 7. Paolo Di Lorenzi 8. Reuse@ 9. Karl Mostert 10. Jim Krieg View All Last 10 characters added: 1. Chancer, Julius 2. Crow, Evelyn 3. The Crow (Brandi) 4. Ghost (Marvel)(02 - Zelc... 5. Maelstrom, Forever 6. Brother Jacob 7. Brother Philip (Firefly) 8. Benitez, Chang 9. Crash Ryan 10. Grud, J. Hoover View All Action Comics (1938) - #744"Crossroads"DC Comics Change this coveror add a variant Writer(s):Stuart Immonen Penciller(s):Anthony Williams Inker(s):Scott KoblishJose Marzan Jr. Colorist(s):Digital ChameleonGlenn Whitmore Letterer(s):Bill Oakley Editor(s):Joey CavalieriMaureen McTigue Cover Artist(s):Ronald 'Ron' FrenzStuart ImmonenPatrick MartinJose Marzan Jr. Rating (out of 10): 8 from 1 voteYou must be logged in to vote! Other members' collections This issue is in 227 collections. This issue is available for sale/trade Toolbox Edit this Issue Clone this Issue View this issue's contribution history Clone the creators of this issue Clone the characters of this issue Suggest a podcast for this issue Search for 'Action Comics' on Amazon Cover Date: May 1998 Cover Price: US $ 1.95 Issue Tagline: None. Format: Color; Standard Comic Issue; 32 pagesStory Arc(s): Add/remove story arcs to this issueBehold! The Millennium Giants!Synopsis: None entered.Reprinted/Collected in:Superman [GER] (1996) #68Superman [ITA] (1993) #121Notes: Continues from Steel (1994) #50. Continues in Superman: The Man of Steel (1994) #79. The covers for each part of the Millennium Giants crossover join together to form one larger image.Characters: Add/remove characters to this issue Alice (DC)(01 - Daily Planet) Aquaman (DC)(Post Crisis)(01-Arthur 'Orin' Curry) Argent (DC) Dirk Armstrong Arsenal (DC)(02 - Roy Harper) Atom (DC)(02 - Ray Palmer) Carrie Axelrod Batman (DC)(03 - Post-Crisis) Cabraca (Millennium Giant) Captain Marvel Jr. (DC)(Post Crisis) Cerne (Millennium Giant) Flash (DC)(03 - Wally West) Fringe Geo-Force (DC) Green Lantern (DC)(05 - Kyle Rayner) Lois Joanne Lane (DC)(Post Crisis) Lena Luthor (DC)(02 - Lex's Daughter) Alexander Joseph 'Lex' Luthor (DC)(Post Crisis) Martian Manhunter (DC) Prysm Risk Sekhmet (Millennium Giant) Steel (DC)(03 - John Henry Irons) Superboy (DC)(Post Crisis)(02 - Conner Kent) Supergirl (DC)(Post Crisis)(02 - Linda Danvers) Superman Blue (DC)(Post Crisis) Superman Red (DC)(Post Crisis) Tempest (DC)(03 - Garth) Terra (DC)(01 - Tara Markov) Ronald Troupe Perry White (DC)(Post Crisis) Groups: Add/remove groups to this issue Justice League of America (DC)Millennium Giants Teen Titans (DC)(02 - Atom's Team) Reviews: There are no reviews for this issue. - Add your review Multiple Stories in this Issue Add a story to this issue Multiple stories do not exist for this issue. © 2005-2019 ComicBookDB.com - Terms and Conditions - Privacy Policy - DMCA Special thanks to Brian Wood for the ComicBookDB.com logo design


text:
However, I have to let loose with a minor ketch...
At almost every event, there is an aspiring writer who has lots of questions. Now, I am more than happy to share my experiences and to give whatever bits of advice I have, but...
I remember reading a great book on writing ,publishing and editing called:
It was a great book and I learned a lot from it. In it, he (I assume Pat is a he) describes a meeting with a wannabe writer - a friend of a friend situation. He agreed to meet with the aspiring author. Turns out, the person only had ideas for a book, but had not actually written anything.
Now, I get it!
Some girl at the signing I did this weekend monopolized my time for a good 20 minutes. I am not an expert on how to write or how to get published, but she decided to pick my brain. (I'm not sure there's much there to pick, but that's another story...)
I was a bit irked - I was in the store to sell books, after all (sold 15, so I guess that's okay). I am still trying to build a reputation, develop an audience and all that. I am happy to share my own experiences, but of course every situation and story is different. Anyhow, this girl kept pushing and badgering me and seemed angry that I wouldn't tell her THE SECRET to getting published.
Finally, I asked her about her writing. Turned out (drum roll please) that she had not written anything yet, she just had an idea for a book.
Now I totally get the Pat Walsh anecdote.
And - I have to say this even if it is cranky - I think it was kind of schmucky of her to gab with me for so long and then not to even buy my book. Kind of rude, IMO.