News around the world (Seite 3137)



Begriffe und/oder Benutzer

 

Antwort auf Beitrag Nr.: 48.383.579 von Popeye82 am 21.11.14 17:58:49
Aberdeen New Thai Investment Trust - EIR - Nov 18, 2014
investmenttrusts@edisongroup.com
+44 (0)20 3681 2503
+44 (0)20 3681 2500
www.edisoninvestmentresearch.com/serve_pdf.php?d=researchrep…
72 Antworten?Die Baumansicht ist in diesem Thread nicht möglich.
Antwort auf Beitrag Nr.: 48.383.732 von Popeye82 am 21.11.14 18:09:11
Solera - EIR - Nov 18, 2014
tech@edisongroup.com
+44 (0)20 3077 5729
www.edisoninvestmentresearch.com/serve_pdf.php?d=researchrep…
71 Antworten?Die Baumansicht ist in diesem Thread nicht möglich.
Genocea Profiles T cell Responses, to Identify Antigens Associated with Malaria Episodes, Findings 'reveal evidence of malaria in immune system years after clinical episodes'
bob.farrell@genocea.com
617-674-8261
http://files.shareholder.com/downloads/AMDA-2GAAWE/365522788…

"Genocea Biosciences, Inc. (NASDAQ: GNCA), a company developing T cell-directed vaccines and immunotherapies, today presented study results identifying a cluster of antigens that may be a biomarker of disease. The findings, generated using Genocea’s proprietary ATLAS™ antigen discovery platform, revealed that malaria leaves a lasting imprint on the immune system. Genocea researchers found evidence that this T cell immunological memory can be detected many years after the previous clinical episode of malaria. The study was presented at the 63rd Annual Meeting of the American Society of Tropical Medicine and Hygiene in New Orleans, LA.


Malaria is caused by Plasmodium falciparum (Pf), a parasite that is transmitted through mosquito bites and rapidly travels to the liver, where it replicates in large numbers and is released into the bloodstream, causing illness. In the current study, the data were collected by analyzing samples from volunteers who recently immigrated to the United States from sub-Saharan Africa, a region where malaria is highly prevalent. Genocea researchers profiled CD8+ T cells from approximately 100 donors against 735 Pf proteins predicted to be expressed in the liver, where CD8+ T cells play a protective role against infection. Study results identified a cluster of 15 antigens that predicted clinical malaria, and may be a biomarker of disease after Pf exposure.

“This is one of the more unexpected findings coming out of our ATLAS™ antigen discovery platform, since immunity to the parasite is thought to be short-lived. Understanding the natural history of responses to diseases as complex as malaria is a necessary first step towards the development of immunotherapies that prevent and treat disease,” said Jessica Baker Flechtner, Ph.D., Genocea’s senior vice president of research. “This finding paves the way for the identification of novel biomarkers indicating Pf exposure, opens avenues for the development of new diagnostic tools, and advances Genocea’s efforts to identify antigens that could form the basis of a future preventative medicine.”

Genocea is collaborating with the Bill and Melinda Gates Foundation to advance the company’s vaccine program. In September 2014, Genocea received a $1.2 million grant from the Gates Foundation for the identification of protective T cell antigens for malaria vaccines, extending the collaboration through 2015.

The poster presented at the meeting (LB-3350) was titled “Profiling of T cell Responses in Recent African Immigrants Identifies a Cluster of Antigens Associated with Clinical Malaria Episodes.”


About Genocea’s Malaria Program

Malaria is one of the deadliest infectious diseases in the world. In 2012, more than 600 million cases of malaria were reported by the World Health Organization (WHO), claiming over 600,000 lives, many of them children and largely in developing countries. There is no licensed vaccine to prevent malaria, an infection caused by Plasmodium parasites transmitted by mosquitoes. When the parasite is injected through the bite of an infected mosquito, it rapidly travels to the liver where it replicates in large numbers and is released into the bloodstream causing sickness. T cells in the liver could potentially kill the cells in which the parasite is hiding before the parasite is able break out into the bloodstream. Genocea’s T cell target discovery platform, ATLAS, is currently being applied to identify which components of the Plasmodium could act as T cell targets and become part of novel vaccine candidates.


About Genocea

Genocea is harnessing the power of T cell immunity to develop life-changing vaccines and immunotherapies. T cells are increasingly recognized as a critical element of protective immune responses to a wide range of diseases, but traditional discovery methods have proven unable to identify the targets of such protective immune response. Using ATLAS™, its proprietary technology platform, Genocea identifies these targets to potentially enable the rapid development of medicines to address critical patient needs. Genocea’s pipeline of novel clinical stage T cell-enabled product candidates includes GEN-003 for HSV-2 therapy, GEN-004 to prevent infections caused by pneumococcus, and earlier-stage programs in chlamydia, HSV-2 prophylaxis, malaria and cancer immunotherapy. For more information, visit www.genocea.com. "
Antwort auf Beitrag Nr.: 48.373.736 von Popeye82 am 20.11.14 19:55:10
ZS Pharma - LifeSci Advisors Update, ZS-9 is 'Poised to Change the Treatment of Hyperkalemia'; Summary of KOL Event - Nov 21, 2014

- Jerry Isaacson, Ph.D.(AC) -

- On November 19th, ZS Pharma (NasdaqGM: ZSPH) hosted a Research and Development day that featured three Key Opinion Leaders (KOLs) from the specialties expected to prescribe ZS-9, an Emergency Medicine physician, a Cardiologist, and a Nephrologist. ZS-9 is being developed to treat hyperkalemia, or excess potassium, with NDA and MAA filings expected in the first half of 2015. Based on their compelling presentations, we came away from the event especially impressed with ZS-9’s rapid onset of action, tolerability profile, and potential for ZS-9 to manage both acute and chronic cases of hyperkalemia, without the safety issues related to current treatments. There are approximately 4 million patients in the US with hyperkalemia, and we estimate that the market opportunity significantly exceeds $1 billion annually in the US alone.


Strong Clinical Data Package Supports Acute and Chronic Hyperkalemia Treatment. ZS Pharma has completed 4 clinical trials with potassium (K+) binder ZS-9, meeting the primary endpoints in all studies. The data consistently demonstrate ZS-9’s ability to safely and rapidly lower serum K+ levels and maintain normokalemia (potassium of 3.5-5 mEq/L). In the most recent trial, the median time to serum K+ normalization was 2.17 hours with greater than 90% of patients receiving 10 or 15 grams of ZS-9 maintained normokalemia for 3 weeks. A 1-year safety study (ZS005) is ongoing. Company management noted that based on extensive discussions with US and European regulators, if ZS Pharma continues to meet trial endpoints, the data would support a label that includes acute and chronic hyperkalemia.


ZS-9 "will" be Revolutionary for the Acute Treatment of Hyperkalemia. Dr. Frank Peacock, an emergency room physician at the largest ER in Houston, TX, discussed the treatment path for an average patient with acute hyperkalemia. His emergency department has extensive experience treating hyperkalemia and sees 30 hyperkalemic patients on a typical day. Most methods for managing serum potassium are temporary and patients ultimately require emergency dialysis. However, the availability of a safe and effective solution to reduce serum potassium rapidly could not only replace existing therapies, but also potentially eliminate the need for emergency dialysis. As the agent with the fastest onset of action, ZS-9 would be very likely be the exclusive agent on his hospital formulary. Importantly, 50% of hyperkalemia patients are first diagnosed in the ER. This represents an entry point for ZS-9 where patients receive initial treatment to normalize K+ levels and then remain on long-term therapy to prevent future acute events.


Expected Upcoming Milestones

​H1 2015 –Expected NDA & MAA submission for ZS-9 for the treatment of hyperkalemia.
H1 2016 –Potential approval and commercial launch of ZS-9.


Huge, Readily Accessible Market Opportunity. Based on 2011 IMS data for the US, 200 million grams of Kayexalate, the current standard of care, are sold annually in the non-retail setting. Using an average 15 gram dose, this represents over 13 million doses of Kayexalate administered in the hospital setting. Given ZS-9’s clinical profile, we expect it to be used as an alternative to Kayexalate, and even using conservative pricing and the capture of only Kayexalate used in hospitals, we believe sales for acute hyperkalemia could reach $300 million annually. Should these acute patients remain on ZS-9 for only a fraction of a year, the product could reach >$1 billion annually.


ZS-9 Data Published in JAMA Shows Significant Benefit for Heart Failure and Chronic Kidney Disease Patients. Cardiologist Dr. Mikhail Kosiborod presented full results from ZS Pharma’s Phase III (ZS004) study at the R&D/KOL event and at the American Heart Association Scientific Meeting last weekend.1 The results were also published in the Journal of the American Medical Association.2 Dr. Kosiborod highlighted the diversity of patients included in the study. The trial enrolled 258 patients with hyperkalemia who were treated with 10 grams of ZS-9 three times per day during a 48 hour acute phase. Patients who achieved normokalemia were randomized to once daily ZS-9 (5, 10, or 15 grams) or placebo for 28 days as part of a randomized withdrawal period. There was no upper limit for baseline serum K+, no lower limit for estimated glomerular filtration rate (eGFR), and the study enrolled patients with many different co-morbidities such as heart failure (HF), chronic kidney disease (CKD), and existing RAAS inhibitor use.

- This trial gives an accurate view of the patients that will be treated in the clinic. ZS-9 displayed similar activity in all subpopulations, confirming its real-world potential as a hyperkalemia treatment. In support of this notion, Dr. Bruce Spinowitz, a Nephrologist, discussed how medications such as RAAS inhibitors can disrupt the body’s K+ balance and trigger hyperkalemia.

- We estimate that 1.4 million CKD and HF patients would benefit from a K+ control agent to enable therapeutic doses of cardio-protective RAAS inhibitor therapy. This represents a staggering multi-billion dollar opportunity.


Excellent Safety Profile Supports Approval. Dr. Kosiborod also presented safety data from trial ZS004, reporting a tolerability profile similar to placebo and no treatment-related serious adverse events. Out of 258 patients, there were 14 cases of edema, 13 were peripheral (foot and ankle) edema, and 7 cases did not require treatment modification. Dr. Kosiborod gave an excellent review of the overall edema cases in all patients treated with ZS-9. Based on his analysis, he believes the single case of generalized edema was likely related to underlying co-morbidities and the fact that the patient recently discontinued their diuretic, and was therefore a false signal. Consistent with the strong safety and tolerability observed in ZS004, ZS Pharma CEO Robert Alexander announced new toxicology data clearly showing that ZS-9 is not systemically absorbed. Dogs treated for 9 months had no detectable ZS-9 in their urine, corresponding to levels at or below parts per billion. This confirms the human data collected in ZS004. Overall the data show that ZS-9 has an excellent safety and tolerability profile.


ZS-9 "will" become the Standard of Care, Despite a Head Start for Patiromer. Relypsa (NasdaqGS: RLYP) is developing a competing product for hyperkalemia, patiromer, which is an organic polymer that exchanges calcium ions (Ca2+) for K+. Relypsa recently filed an NDA for patiromer. There are several features of ZS-9 that set it apart from patiromer and will make it the standard of care:

- Rapid onset of action: Statistically significant reduction in serum potassium by 1 hour for ZS-9 compared to 7 hours for patiromer.
- Convenient dosing: ZS-9 is a once daily treatment for maintenance of hyperkalemia compared to twice daily for patiromer.
- Strong tolerability profile: The rate of GI side effects from ZS-9 is similar to placebo compared to higher rates of diarrhea, constipation, and nausea for patiromer.
- High ion selectivity: ZS-9 is highly selective for potassium whereas patiromer can non-specifically bind other ions including magnesium.


Ion Selectivity/Release Deserves Scrutiny. The ion selectivity/release of each compound in particular may have profound implications for extended use. Hypomagnesemia occurred in 24% of patients taking 15 grams of patiromer twice daily in a trial with heart failure patients,3 and there were 8 cases (3%) in the induction phase of Relypsa’s Phase III study. Patiromer’s mechanism of action is to exchange Ca2+ for K+. Calcium is found in vascular deposits that are more likely to occur in CKD patients due to imbalances in bone metabolism. The deposits can contribute to the development of heart disease. For these reasons, CKD patients are often prescribed non-calcium based phosphate binders to manage hyperphosphatemia and minimize new calcium deposition in the arteries.4 Although Relypsa has not reported elevations in serum Ca2+from its clinical studies, patiromer approximately contains 3,200 mg of Ca2+ in a daily dose. The Cleveland Clinic recommends Ca2+ intake of 1,400-1,600 mg/day, not to exceed 2,000 mg/day, for patients with CKD. Most Ca2+ comes from dietary intake, and the long-term exposure to additional Ca2+ via patiromer may represent an issue for CKD patients, which make up the majority of hyperkalemia cases. ...-
jisaacson@lifescicapital.com
(646) 597-6991
https://lifesci.bluematrix.com/sellside/EmailDocViewer?encry…
3 Antworten?Die Baumansicht ist in diesem Thread nicht möglich.
Minotaur Exploration - High-grade mineralisation continues @Artemis, drills 'up to' 16.14m @3.29% Cu, 2.98g/t Au, 6.61% Zn, 1.77% Pb, 65g/t Ag +0.32% Co - Nov 20, 2014
www.minotaurexploration.com.au/sites/default/files/MinotaurA…
Antwort auf Beitrag Nr.: 47.989.222 von Popeye82 am 09.10.14 19:11:58
Cynapsus Therapeutics Announces Positive Top-Line Results from CTH-105 Phase 2 Study of APL-130277, Clinically meaningful improvement in motor control occurred in as early as 10 minutes after administration of APL-130277 +lasted >90 minutes, Conference call begins @8:00 a.m. Eastern time today - Nov 19, 2014
ajg@cynapsus.ca
(416) 703-2449 x225
awilliams@cynapsus.ca
(416) 703-2449 x253
www.cynapsus.ca/melonhead/media/1416405230.pdf
www.media-server.com/m/p/7gtq5eyh
www.cynapsus.ca/news.php?article=331

"TORONTO (BUSINESS WIRE) – Cynapsus Therapeutics Inc. (CTH: TSX-V) (CYNAF: OTCQX), a specialty pharmaceutical company focused on Parkinson’s disease, today announced positive top-line results from its CTH-105 Phase 2 clinical trial of APL-130277 for the management of OFF motor symptoms of Parkinson’s disease.

APL-130277 is the Company’s fast-acting, sublingual, thin filmstrip formulation of apomorphine. OFF episodes are a complication of Parkinson’s disease that leave patients rigid and unable to move and communicate. An estimated one quarter to one half of all people with Parkinson’s disease whose symptoms are otherwise managed with ongoing drug therapy, experience OFF episodes at least once daily and up to six times daily, with each episode lasting between 30 and 120 minutes.


Highlights of the CTH-105 study results include:

- Out of 16 patients treated with APL-130277, 14 converted from OFF to ON, suggesting that APL-130277 may effectively manage OFF episodes in patients with Parkinson’s disease
- Preliminary data show that several subjects converted to ON with the 10mg low dose, and 14 of 16 subjects converted ON with all available doses (i.e. 10, 15, 20, 25 and 30mg)
- Clinically meaningful improvement in motor control occurred in as early as 10 minutes after administration of APL-130277 and lasted longer than 90 minutes
- The maximum mean change from baseline UPDRS III was 18.4, which is a large clinically important difference
- APL-130277 treatment was safe and well tolerated, with no local irritation, no postural hypotension and a low number of nausea events


“The purpose of the CTH-105 study was to better understand the APL-130277 dose range that produced efficacy as measured by the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, a scale used by neurologists to measure the severity of Parkinson’s disease OFF and motor symptoms, compared with baseline. We are encouraged that APL-130277 provided clinical benefit at all five doses used in this study,” said Dr. Albert Agro, Chief Medical Officer of Cynapsus. “These preliminary data show that APL-130277 was able to convert patients from a severe OFF state in the morning to ON. In addition, treatment was associated with a 45% improvement in motor function based on the change in UPDRS part III from baseline. The mean dose needed to terminate the OFF episode was 18.4mg. In addition, those patients achieving a response at higher doses appeared to adapt to the treatment, as seen by the lack of nausea at higher doses.”


Phase 2 Study Design

In the CTH-105 multicenter open-label study, APL-130277 was assessed in 16 patients with Parkinson’s disease who experience the debilitating effects of OFF episodes, with a total duration of OFF of at least two hours daily. To date, 16 patients have completed the dosing regimen, which was the planned sample size for the study. Due to over enrollment, an additional three patients are still in dosing. OFF episodes were achieved by having patients take their last dose of levodopa the night before they came into the clinic. Patients were not allowed to take their first dose of levodopa in the morning, resulting in a severe OFF state that is one of the most difficult to convert and maintain in an ON state. Patients were then given escalating doses of APL-130277 (at a minimum of three hours between doses) until ON was achieved, as documented by study staff, the patient, and a clinician assessment of UPDRS part III. The UPDRS III part score was measured at 15, 30, 45, 60 and 90 minutes.


Phase 2 Study Results

All five doses of APL-130277 used in the study (10, 15, 20, 25 and 30mg) resulted in patients moving from OFF to ON. The mean baseline UPDRS part III in an OFF state was 41.4, and the maximum mean change from baseline UPDRS part III was 18.4. The mean dose required to convert patients to ON was 18.4mg. The onset of a clinically meaningful improvement was seen in as early as 10 minutes and lasted up to 90 minutes, the last time point measured in this study. The mean time to ON as reported by study staff was 22 minutes. Cynapsus believes that these data strongly support the conclusion that APL-130277 is associated with the robust and rapid management of OFF episodes.

The graph below shows the mean change from baseline in UPDRS part III for the 14 subjects who converted to ON. Two patients dosed at the highest available dose (30mg) did not achieve a full ON as assessed by the investigator, suggesting that higher doses may be required for some patients.


Mean Change in UPDRS Part III from Baseline Over Study Period, for Patients Converting from OFF to ON




Treatment with APL-130277 was safe and well tolerated. Nausea was reported by three subjects at doses of 10, 15 and 20mg. One of these patients also experienced a mild episode of emesis. There were no reports of nausea at higher doses. There were no reports of local irritation or hypotension in any subject treated. A total of 60 doses of APL-130277 were administered to the 16 patients who completed dosing in the CTH-105 study.

Based on the findings of this study, Cynapsus is planning to conduct pivotal studies of longer duration and with larger patient numbers to confirm these results. These pivotal studies are expected to form the registration package necessary for a 505(b)(2) New Drug Application with the U.S. Food and Drug Administration expected to be submitted in 2016.

“The results of this Phase 2 trial are important as the data show that APL-130277 provided Parkinson’s patients with a rapid improvement in motor function during OFF episodes,” said Anthony Giovinazzo, President and CEO of Cynapsus. “APL-130277 is being developed to address a significant unmet need facing people with Parkinson’s disease today. The CTH-105 trial results lead us to maintain that APL-130277 may be able to serve the majority of Parkinson’s patients seeking to restore movement rapidly, on demand, with an easy to retrieve and to administer form of apomorphine, the only approved and most efficacious drug for this purpose.”

“OFF episodes are debilitating events for people with Parkinson’s disease. A recent survey by The Michael J. Fox Foundation of 3,000 Parkinson’s patients revealed that nearly half said their OFF time was moderate or severe, causing them to avoid or stop activities," said Dr. Todd Sherer, CEO of The Michael J. Fox Foundation for Parkinson's Research, which provided $500,000 in funding for this study. “A rapid and reliable therapy that can address OFF episodes would be a major advancement in treatment. These results suggest that APL-130277 could provide patients with improved quality of life, and as supporters of this program from its early days, we look forward to continued success in Phase 3 trials.”


About Parkinson’s Disease and OFF Episodes

More than 1 million people in the U.S. and an estimated 4 to 6 million people globally suffer from Parkinson's disease. Parkinson’s disease is a chronic and progressive neurodegenerative disease that impacts motor activity, and its prevalence is increasing with the aging of the population. OFF episodes are a complication of Parkinson’s disease that leave patients rigid and unable to move and communicate. An estimated one quarter to one half of all people with Parkinson’s disease whose symptoms are otherwise managed with ongoing drug therapy experience OFF episodes at least once daily and up to six times daily, with each episode lasting between 30 and 120 minutes.

OFF and motor symptoms of Parkinson’s disease are measured by UPDRS part III. The UPDRS is used by neurologists to measure the severity of Parkinson’s disease.


About Apomorphine

Apomorphine is the only drug that can rapidly convert a patient from OFF (unable to move) to ON (fully functional). Unfortunately for Parkinson’s patients, apomorphine is currently only available only as an injection, which can be painful and difficult to administer, particularly while suffering an OFF episode.

Cynapsus’ APL-130277 drug candidate is the only oral formulation of apomorphine for the treatment of OFF episodes. APL-130277 is a strip that a Parkinson’s patient can place under his or her tongue when an OFF episode is starting. If approved, APL‐130277 will provide patients with a convenient and easy alternative to multiple daily injections.


Conference Call and Webcast

Cynapsus management will host a conference call with accompanying slides to discuss these findings and answer questions today at 8:00 a.m. Eastern time. Shareholders and other interested parties can participate in the call by dialing 888-883-4599 (domestic) or 484-653-6821 (international) and referencing conference ID number 37666252. The call and slides will also be webcast live on the Company's website at www.cynapsus.ca on the Calendar and Alerts page under Investor Relations.

A replay of the conference call will be accessible beginning two hours after its completion through November 26, 2014 by dialing 855-859-2056 (domestic) or 404-537-3406 (international) and referencing conference ID number 37666252. The call and slides will also be archived for 90 days on the Company's website at www.cynapsus.ca on the Calendar and Alerts page under Investor Relations.


About Cynapsus Therapeutics

Cynapsus is a specialty pharmaceutical company developing a sublingual thin filmstrip for the acute rescue of OFF motor symptoms of Parkinson’s disease. Cynapsus’ drug candidate, APL-130277, is an easy-to-use, fast-acting formulation of apomorphine, which is the only approved drug (in the United States, Europe, Japan and other countries) to rescue patients from OFF episodes. Cynapsus is focused on maximizing the value of APL-130277 by completing pivotal studies in advance of a 505(b)(2) New Drug Application (NDA) expected to be submitted in 2016.

More information about Cynapsus is available at www.cynapsus.ca and at the System for Electronic Document Analysis and Retrieval (SEDAR) at www.sedar.com. "
Antwort auf Beitrag Nr.: 48.384.344 von Popeye82 am 21.11.14 18:58:52
Zitat von Popeye82: ZS Pharma - LifeSci Advisors Update, ZS-9 is 'Poised to Change the Treatment of Hyperkalemia'; Summary of KOL Event - Nov 21, 2014

- Jerry Isaacson, Ph.D.(AC) -

- On November 19th, ZS Pharma (NasdaqGM: ZSPH) hosted a Research and Development day that featured three Key Opinion Leaders (KOLs) from the specialties expected to prescribe ZS-9, an Emergency Medicine physician, a Cardiologist, and a Nephrologist. ZS-9 is being developed to treat hyperkalemia, or excess potassium, with NDA and MAA filings expected in the first half of 2015. Based on their compelling presentations, we came away from the event especially impressed with ZS-9’s rapid onset of action, tolerability profile, and potential for ZS-9 to manage both acute and chronic cases of hyperkalemia, without the safety issues related to current treatments. There are approximately 4 million patients in the US with hyperkalemia, and we estimate that the market opportunity significantly exceeds $1 billion annually in the US alone.


Strong Clinical Data Package Supports Acute and Chronic Hyperkalemia Treatment. ZS Pharma has completed 4 clinical trials with potassium (K+) binder ZS-9, meeting the primary endpoints in all studies. The data consistently demonstrate ZS-9’s ability to safely and rapidly lower serum K+ levels and maintain normokalemia (potassium of 3.5-5 mEq/L). In the most recent trial, the median time to serum K+ normalization was 2.17 hours with greater than 90% of patients receiving 10 or 15 grams of ZS-9 maintained normokalemia for 3 weeks. A 1-year safety study (ZS005) is ongoing. Company management noted that based on extensive discussions with US and European regulators, if ZS Pharma continues to meet trial endpoints, the data would support a label that includes acute and chronic hyperkalemia.


ZS-9 "will" be Revolutionary for the Acute Treatment of Hyperkalemia. Dr. Frank Peacock, an emergency room physician at the largest ER in Houston, TX, discussed the treatment path for an average patient with acute hyperkalemia. His emergency department has extensive experience treating hyperkalemia and sees 30 hyperkalemic patients on a typical day. Most methods for managing serum potassium are temporary and patients ultimately require emergency dialysis. However, the availability of a safe and effective solution to reduce serum potassium rapidly could not only replace existing therapies, but also potentially eliminate the need for emergency dialysis. As the agent with the fastest onset of action, ZS-9 would be very likely be the exclusive agent on his hospital formulary. Importantly, 50% of hyperkalemia patients are first diagnosed in the ER. This represents an entry point for ZS-9 where patients receive initial treatment to normalize K+ levels and then remain on long-term therapy to prevent future acute events.


Expected Upcoming Milestones

​H1 2015 –Expected NDA & MAA submission for ZS-9 for the treatment of hyperkalemia.
H1 2016 –Potential approval and commercial launch of ZS-9.


Huge, Readily Accessible Market Opportunity. Based on 2011 IMS data for the US, 200 million grams of Kayexalate, the current standard of care, are sold annually in the non-retail setting. Using an average 15 gram dose, this represents over 13 million doses of Kayexalate administered in the hospital setting. Given ZS-9’s clinical profile, we expect it to be used as an alternative to Kayexalate, and even using conservative pricing and the capture of only Kayexalate used in hospitals, we believe sales for acute hyperkalemia could reach $300 million annually. Should these acute patients remain on ZS-9 for only a fraction of a year, the product could reach >$1 billion annually.


ZS-9 Data Published in JAMA Shows Significant Benefit for Heart Failure and Chronic Kidney Disease Patients. Cardiologist Dr. Mikhail Kosiborod presented full results from ZS Pharma’s Phase III (ZS004) study at the R&D/KOL event and at the American Heart Association Scientific Meeting last weekend.1 The results were also published in the Journal of the American Medical Association.2 Dr. Kosiborod highlighted the diversity of patients included in the study. The trial enrolled 258 patients with hyperkalemia who were treated with 10 grams of ZS-9 three times per day during a 48 hour acute phase. Patients who achieved normokalemia were randomized to once daily ZS-9 (5, 10, or 15 grams) or placebo for 28 days as part of a randomized withdrawal period. There was no upper limit for baseline serum K+, no lower limit for estimated glomerular filtration rate (eGFR), and the study enrolled patients with many different co-morbidities such as heart failure (HF), chronic kidney disease (CKD), and existing RAAS inhibitor use.

- This trial gives an accurate view of the patients that will be treated in the clinic. ZS-9 displayed similar activity in all subpopulations, confirming its real-world potential as a hyperkalemia treatment. In support of this notion, Dr. Bruce Spinowitz, a Nephrologist, discussed how medications such as RAAS inhibitors can disrupt the body’s K+ balance and trigger hyperkalemia.

- We estimate that 1.4 million CKD and HF patients would benefit from a K+ control agent to enable therapeutic doses of cardio-protective RAAS inhibitor therapy. This represents a staggering multi-billion dollar opportunity.


Excellent Safety Profile Supports Approval. Dr. Kosiborod also presented safety data from trial ZS004, reporting a tolerability profile similar to placebo and no treatment-related serious adverse events. Out of 258 patients, there were 14 cases of edema, 13 were peripheral (foot and ankle) edema, and 7 cases did not require treatment modification. Dr. Kosiborod gave an excellent review of the overall edema cases in all patients treated with ZS-9. Based on his analysis, he believes the single case of generalized edema was likely related to underlying co-morbidities and the fact that the patient recently discontinued their diuretic, and was therefore a false signal. Consistent with the strong safety and tolerability observed in ZS004, ZS Pharma CEO Robert Alexander announced new toxicology data clearly showing that ZS-9 is not systemically absorbed. Dogs treated for 9 months had no detectable ZS-9 in their urine, corresponding to levels at or below parts per billion. This confirms the human data collected in ZS004. Overall the data show that ZS-9 has an excellent safety and tolerability profile.


ZS-9 "will" become the Standard of Care, Despite a Head Start for Patiromer. Relypsa (NasdaqGS: RLYP) is developing a competing product for hyperkalemia, patiromer, which is an organic polymer that exchanges calcium ions (Ca2+) for K+. Relypsa recently filed an NDA for patiromer. There are several features of ZS-9 that set it apart from patiromer and will make it the standard of care:

- Rapid onset of action: Statistically significant reduction in serum potassium by 1 hour for ZS-9 compared to 7 hours for patiromer.
- Convenient dosing: ZS-9 is a once daily treatment for maintenance of hyperkalemia compared to twice daily for patiromer.
- Strong tolerability profile: The rate of GI side effects from ZS-9 is similar to placebo compared to higher rates of diarrhea, constipation, and nausea for patiromer.
- High ion selectivity: ZS-9 is highly selective for potassium whereas patiromer can non-specifically bind other ions including magnesium.


Ion Selectivity/Release Deserves Scrutiny. The ion selectivity/release of each compound in particular may have profound implications for extended use. Hypomagnesemia occurred in 24% of patients taking 15 grams of patiromer twice daily in a trial with heart failure patients,3 and there were 8 cases (3%) in the induction phase of Relypsa’s Phase III study. Patiromer’s mechanism of action is to exchange Ca2+ for K+. Calcium is found in vascular deposits that are more likely to occur in CKD patients due to imbalances in bone metabolism. The deposits can contribute to the development of heart disease. For these reasons, CKD patients are often prescribed non-calcium based phosphate binders to manage hyperphosphatemia and minimize new calcium deposition in the arteries.4 Although Relypsa has not reported elevations in serum Ca2+from its clinical studies, patiromer approximately contains 3,200 mg of Ca2+ in a daily dose. The Cleveland Clinic recommends Ca2+ intake of 1,400-1,600 mg/day, not to exceed 2,000 mg/day, for patients with CKD. Most Ca2+ comes from dietary intake, and the long-term exposure to additional Ca2+ via patiromer may represent an issue for CKD patients, which make up the majority of hyperkalemia cases. ...-
jisaacson@lifescicapital.com
(646) 597-6991
https://lifesci.bluematrix.com/sellside/EmailDocViewer?encry…
Antwort auf Beitrag Nr.: 48.269.191 von Popeye82 am 09.11.14 23:58:37
Biochemists build largest synthetic molecular 'cage' ever - NW/UCLA, CNSI/NC/DoE/NIoH, CALIFORNIA - Nov 19, 2014
www.nature.com/nchem/journal/v6/n12/full/nchem.2107.html
www.nanowerk.com/nanotechnology-news/newsid=38171.php

"UCLA biochemists have created the largest-ever protein that self-assembles into a molecular "cage." The research could lead to synthetic vaccines that protect people from the flu, HIV and other diseases.


At a size hundreds of times smaller than a human cell, it also could lead to new methods of delivering pharmaceuticals inside of cells, or to the creation of new nanoscale materials.


The protein assembly, which is shaped like a cube, was constructed from 24 copies of a protein designed in the laboratory of Todd Yeates, a UCLA professor of chemistry and biochemistry. It is porous -- more so than any other protein assembly ever created -- with large openings that would enable other large protein molecules to enter and exit.

The research was recently published online in the journal Nature Chemistry ("Structure of a designed protein cage that self-assembles into a highly porous cube") and will appear in a future print edition.




- This is a molecular cage created by designing specialized protein pieces. On the left is one copy of the designed protein molecule. The 24 copies of it on the right, each colored differently, make the molecular cage. The lavender image on the right indicates the openness of the empty space in the middle of the container and is not actually part of the molecular structure. (Image: Yen-Ting Lai, Todd Yeates) -


Yeates, the study's senior author, has sought to build complex protein structures that self-assemble since he first published research on self-assembling proteins in 2001. In 2012, he and colleagues produced a self-assembling molecular cage made from 12 protein pieces combined perfectly like pieces of a puzzle. Now they have done so with 24 pieces, and they are currently attempting to design a molecular cage with 60 pieces. Building each larger protein presented new scientific challenges, but the bigger sizes could potentially carry more "cargo."

In principle, these molecular structures should be able to carry cargo that could then be released inside of cells, said Yeates, who is a member of the UCLA-Department of Energy Institute of Genomics and Proteomics and the California NanoSystems Institute at UCLA.

Yeates' research was funded by the National Science Foundation and the UCLA-DOE Institute of Genomics and Proteomics. The lead author was Yen-Ting Lai, who conducted the research as a UCLA graduate student in Yeates' laboratory and is now a postdoctoral scholar at Arizona State University.

The molecular cube is probably too porous to serve as a container -- for medicine, for example -- inside a human body. "But the design principles for making a cage that is more closed would be the same," Yeates said, adding that there are ways to make the cage less stable when it gets into a cell, so that it would release its cargo, such as a toxin that could kill a cancer cell.

Yeates said that his lab's method also could lead to the production of synthetic vaccines that would mimic what a cell sees when it's infected by a virus. The vaccines would provoke a strong response from the body's immune system and perhaps provide better protection from diseases than traditional vaccines.

Yeates has started a research collaboration with Peter Kwong, chief of the structural biology section at the National Institutes of Health and a national leader in the structural biology of disease viruses. They will conduct research on attaching viral antigens to molecular cages.


Source: UCLA "
40 Antworten?Die Baumansicht ist in diesem Thread nicht möglich.
Antwort auf Beitrag Nr.: 48.386.516 von Popeye82 am 21.11.14 23:59:55
'Mind the Gap' between atomically thin materials, When it comes to engineering single-layer atomic structures, minding the gap will help researchers create artificial electronic materials one atomic layer @a time - NW/PSMRI/NL - Nov 21, 2014
www.nanowerk.com/nanotechnology-news/newsid=38202.php?utm_so…
http://pubs.acs.org/doi/abs/10.1021/nl503144a

"In subway stations around London, the warning to “Mind the Gap” helps commuters keep from stepping into empty space as they leave the train. When it comes to engineering single-layer atomic structures, minding the gap will help researchers create artificial electronic materials one atomic layer at a time.


The gap is a miniscule vacuum that can only be seen under a high-power transmission electron microscope. The gap, researchers in Penn State’s Center for 2-Dimensional and Layered Materials (2DLM) believe, is an energy barrier that keeps electrons from easily crossing from one layer of material to the next.




- Colorized TEM image of tungsten disulfide triangles (black) growing on graphene substrate (green). -


“It’s a natural insulating layer Mother Nature built into these artificially created materials,” said Joshua Robinson, assistant professor of materials science and engineering and associate director of the 2DLM Center. “We’re still trying to understand how electrons move vertically through these layered materials, and we thought it should take a lot less energy. Thanks to a combination of theory and experiment, we now know we have to account for this gap when we design new materials.”

For the first time, the Penn State researchers grew a single atomic layer of tungsten diselenide on a one- atom-thick substrate of graphene with pristine interfaces between the two layers. When they tried to put a voltage from the top tungsten diselenide (WSe2) layer down to the graphene layer, they encountered a surprising amount of resistance. About half of the resistance was caused by the gap, which introduced a large barrier, about 1 electron volt (1eV), to the electrons trying to move between layers. This energy barrier could prove useful in designing next generation electronic devices, such as vertical tunneling field effect transistors, Robinson said.

The interest in these van der Waals materials arose with the discovery of methods to make single layer graphite by using Scotch tape to mechanically cleave a one-atom-thick layer of carbon called graphene from bulk graphite. The van der Waals force that binds layers of graphite together is weak enough to allow stripping of the single atomic layer. The Penn State researchers use a different, more scalable method, called chemical vapor deposition, to deposit a single layer of crystalline WSe2 on top of a few layers of epitaxial graphene that is grown from silicon carbide. Although graphene research exploded in the last decade, there are many van der Waal solids that can be combined to create entirely new artificial materials with unimaginable properties.

In a paper published online this month in Nano Letters ("Atomically Thin Heterostructures Based on Single-Layer Tungsten Diselenide and Graphene"), the Penn State team and colleagues from UT Dallas, the Naval Research Laboratory, Sandia National Lab, and labs in Taiwan and Saudi Arabia, discovered that the tungsten diselenide layer grew in perfectly aligned triangular islands 1-3 microns in size that slowly coalesced into a single crystal up to 1 centimeter square. Robinson believes it will be possible to grow these crystals to industrially useful wafer-scale sizes, although will require a larger furnace than he currently has in his lab.

“One of the really interesting things about this gap,” Robinson said, “is that it allows us to grow aligned layers despite the fact that the atoms in the graphene are not lined up with the atoms in the tungsten diselenide. In fact there is a 23 percent lattice mismatch, which is huge. Mother Nature really relaxed the rules when it comes to these big differences in atom spacing.”


Source: Penn State Materials Research Institute "
Antwort auf Beitrag Nr.: 48.386.516 von Popeye82 am 21.11.14 23:59:55
'Mind the Gap' between atomically thin materials, When it comes to engineering single-layer atomic structures, minding the gap will help researchers create artificial electronic materials one atomic layer @a time - NW/PSMRI/NL - Nov 21, 2014
www.nanowerk.com/nanotechnology-news/newsid=38202.php?utm_so…
http://pubs.acs.org/doi/abs/10.1021/nl503144a

"In subway stations around London, the warning to “Mind the Gap” helps commuters keep from stepping into empty space as they leave the train. When it comes to engineering single-layer atomic structures, minding the gap will help researchers create artificial electronic materials one atomic layer at a time.


The gap is a miniscule vacuum that can only be seen under a high-power transmission electron microscope. The gap, researchers in Penn State’s Center for 2-Dimensional and Layered Materials (2DLM) believe, is an energy barrier that keeps electrons from easily crossing from one layer of material to the next.




- Colorized TEM image of tungsten disulfide triangles (black) growing on graphene substrate (green). -


“It’s a natural insulating layer Mother Nature built into these artificially created materials,” said Joshua Robinson, assistant professor of materials science and engineering and associate director of the 2DLM Center. “We’re still trying to understand how electrons move vertically through these layered materials, and we thought it should take a lot less energy. Thanks to a combination of theory and experiment, we now know we have to account for this gap when we design new materials.”

For the first time, the Penn State researchers grew a single atomic layer of tungsten diselenide on a one- atom-thick substrate of graphene with pristine interfaces between the two layers. When they tried to put a voltage from the top tungsten diselenide (WSe2) layer down to the graphene layer, they encountered a surprising amount of resistance. About half of the resistance was caused by the gap, which introduced a large barrier, about 1 electron volt (1eV), to the electrons trying to move between layers. This energy barrier could prove useful in designing next generation electronic devices, such as vertical tunneling field effect transistors, Robinson said.

The interest in these van der Waals materials arose with the discovery of methods to make single layer graphite by using Scotch tape to mechanically cleave a one-atom-thick layer of carbon called graphene from bulk graphite. The van der Waals force that binds layers of graphite together is weak enough to allow stripping of the single atomic layer. The Penn State researchers use a different, more scalable method, called chemical vapor deposition, to deposit a single layer of crystalline WSe2 on top of a few layers of epitaxial graphene that is grown from silicon carbide. Although graphene research exploded in the last decade, there are many van der Waal solids that can be combined to create entirely new artificial materials with unimaginable properties.

In a paper published online this month in Nano Letters ("Atomically Thin Heterostructures Based on Single-Layer Tungsten Diselenide and Graphene"), the Penn State team and colleagues from UT Dallas, the Naval Research Laboratory, Sandia National Lab, and labs in Taiwan and Saudi Arabia, discovered that the tungsten diselenide layer grew in perfectly aligned triangular islands 1-3 microns in size that slowly coalesced into a single crystal up to 1 centimeter square. Robinson believes it will be possible to grow these crystals to industrially useful wafer-scale sizes, although will require a larger furnace than he currently has in his lab.

“One of the really interesting things about this gap,” Robinson said, “is that it allows us to grow aligned layers despite the fact that the atoms in the graphene are not lined up with the atoms in the tungsten diselenide. In fact there is a 23 percent lattice mismatch, which is huge. Mother Nature really relaxed the rules when it comes to these big differences in atom spacing.”


Source: Penn State Materials Research Institute "
38 Antworten?Die Baumansicht ist in diesem Thread nicht möglich.
 Durchsuchen


Beitrag zu dieser Diskussion schreiben