AZ News from the Street 2015

More from AZ at ASCO:


AstraZeneca Updates on Immuno-Oncology Combinations Development Program at ASCO 2015
Business Wire
AstraZeneca
54 minutes ago

WILMINGTON, Del.--(BUSINESS WIRE)--

AstraZeneca (AZN) and MedImmune, the Company’s global biologics research and development arm, provided an update on the progress of their combination-focused immuno-oncology pipeline at an investor science event at the American Society of Clinical Oncology (ASCO) meeting in Chicago on June 1, 2015.

Commenting on the Company’s immuno-oncology combination data presented at ASCO, Chief Executive Officer, Pascal Soriot, said: “Immuno-oncology has continued to take center stage at ASCO this year, as we see more evidence of the significance of this approach for patients. At AstraZeneca we have been clear in our belief that combinations hold the key to transforming clinical practice for the patients not benefiting from the currently-available immunotherapies. The data presented on the combination of MEDI4736 and tremelimumab are truly exciting. As the frontrunner combination of two immuno-oncology molecules in non-small cell lung cancer, it is demonstrating promising clinical activity, in particular in the majority of patients who have low or no PD-L1 expression. With our longstanding expertise in developing small molecule medicines, including olaparib and AZD9291, we are now also seeing the potential of combining these targeted medicines with immuno-oncology molecules to deliver efficacious and durable treatment to patients.”

Highlights of the update were:

Data presented on MEDI4736, the Company’s anti-PD-L1 monoclonal antibody, as monotherapy in heavily pre-treated patients with non-small cell lung cancer (NSCLC) are encouraging and suggest that patients with PD-L1 positive tumors may have an improved overall response rate compared to patients with PD-L1 negative tumors, highlighting the unmet medical need for the majority of tumors that are PD-L1 negative.
MEDI4736 is demonstrating strong potential to combine with both immunotherapy and small molecules; AstraZeneca and MedImmune have an extensive development program underway across multiple tumor types and stages of disease, assessing the potential for immunotherapy to either replace or combine with traditional chemotherapy.

Immuno-oncology combinations

The combination of MEDI4736 and tremelimumab (anti-CTLA-4 monoclonal antibody) is demonstrating efficacy regardless of PD-L1 status, showing promise for the significant number of patients who fail to respond to anti-PD-1/PD-L1 monotherapy because of their PD-L1 biomarker negative status.
The combination of MEDI4736 and tremelimumab is also showing a manageable safety profile, with a discontinuation rate due to related adverse events of only 7%.
Nine immuno-oncology clinical trials are planned and underway in NSCLC across early (adjuvant and unresectable stage III) and advanced stages of the disease, including three new studies in first-line metastatic NSCLC announced at ASCO, assessing MEDI4736 in combination with tremelimumab or with chemotherapy.
AstraZeneca is exploring the potential clinical benefit of the combination of MEDI4736 and tremelimumab in additional tumor types including squamous cell carcinoma of the head and neck (SCCHN), and announced new tumor types, including gastric, pancreatic and bladder cancer, with the aim of changing the treatment paradigm for patients with a chemotherapy-free regimen.
Other immuno-oncology combinations are being explored with the Company’s three OX40 molecules in advanced solid and haematological malignancies, with the optimal potential medicine to be selected by the end of 2015.

Immuno-oncology and small molecule combinations

The combination of targeted therapy and immune checkpoint inhibitors has the potential to offer higher response rates and extended duration of responses.
MEDI4736 has been shown to be well tolerated in combination at full dose with multiple tyrosine kinase inhibitors (TKIs), with encouraging preliminary efficacy data, including:

MEDI4736 and BRAF and MEK inhibitors - early data shows encouraging confirmed partial response (69%) and disease control rate (100%).
MEDI4736 and AZD9291 - early data indicates the molecules are well tolerated in combination at their Phase III doses, providing early promise of a potential new standard of care in EGFR mutation (EGFRm) and T790M positive NSCLC. EGFR remains one of the major tumor drivers despite progression on EGFR TKIs.
MEDI4736 and gefitinib – early data in EGFRm TKI-naïve NSCLC shows a 64% (9/14) partial response rate. The combination is planned for Phase III study in first line EGFRm NSCLC.
In addition, combination trials of MEDI4736 and olaparib are planned to start by the third quarter in 2015.

 

Shopping?

AstraZeneca’s Soriot Open to Buying Immune-Therapy Company
by Oliver Staley
June 2, 2015 — 10:20 AM EDT
Updated on June 2, 2015 — 1:25 PM EDT

AstraZeneca Plc would consider acquiring a developer of a new type of cancer therapy aimed at supercharging the body’s immune response, Chief Executive Officer Pascal Soriot said.

“If at some point we conclude we need to make an acquisition, we certainly would consider it, there’s no question about it,” Soriot said in an interview, in response to a question about whether AstraZeneca would consider buying a CAR T asset such as Juno Therapeutics Inc. Juno went public last year and is valued at about $4.8 billion.

Juno shares soared as much as 16 percent.

AstraZeneca, based in London, is collaborating with Juno, a Seattle startup, to combine its immune therapy drug with Juno’s CAR T treatment. CAR T is one of the hottest areas in health care, producing unprecedented responses in patients and boosting shares of biotechnology companies such as Kite Pharma Inc. and Bluebird Bio Inc.

Soriot said an acquisition isn’t imminent.

“At this stage, we have a lot on our hands,” the CEO said. “We have a full portfolio of immunoncology assets; our strategy has been, with CAR T, to partner.”

Juno rose 14 percent to $60.40 as of 1:22 p.m. in New York trading. The stock has more than doubled since its initial public offering in December. AstraZeneca’s stock dropped 0.2 percent by the close in London trading.

CAR T, for chimeric antigen receptor therapy, works by removing a patient’s disease-fighting T cells and re-engineering them to attack cancer cells. In some trials of children with a common form of leukemia, early signs of the cancer disappeared in 90 percent of the patients. The reintroduced T cells can also trigger serious side effects, including an immune reaction that can be fatal.

The side effects would have to be managed before AstraZeneca would make an acquisition, Soriot said.

“The CAR T technology has a lot of promises; we also need to find a way to manage the side effects,” he said. “They can be hard to predict and they can be quite substantial.”

(An earlier version was corrected to show Soriot was responding to a question about whether the company was interested in making an acquisition in CAR T therapies such as Juno.)

 

This project apparently crapped out:


Ardelyx Regains Worldwide Development and Commercialization Rights for Its Late-Stage Development Candidate, Tenapanor, and Related Portfolio of NHE3 Compounds.

Ardelyx to Initiate a Phase 3 Clinical Program in IBS-C Patients in the Fourth Quarter of 2015

PR Newswire Ardelyx
3 hours ago

FREMONT, Calif., June 3, 2015 /PRNewswire/ -- Ardelyx, Inc. (ARDX), a clinical-stage biopharmaceutical company focused on cardio-renal, gastrointestinal and metabolic diseases, today announced that it has entered into a termination agreement with AstraZeneca (LSE: AZN, SSE: AZN, NYSE: AZN), such that all the rights to Ardelyx's portfolio of NHE3 inhibitors, including Ardelyx's lead product candidate, tenapanor, are returned to Ardelyx. Ardelyx has agreed to pay AstraZeneca $15 million upfront along with other future contingent payments. Concurrently, Ardelyx will pay an additional $10 million in R&D costs and for the acceleration of the transfer of the program back to Ardelyx. Ardelyx formed a partnership with AstraZeneca in October 2012 to develop and commercialize Ardelyx's internally discovered portfolio of NHE3 inhibitors including tenapanor.

With the acquisition of worldwide rights from AstraZeneca, Ardelyx plans to accelerate the clinical development path for tenapanor in constipation-predominant irritable bowel syndrome (IBS-C) by initiating a Phase 3 clinical program in IBS-C patients in the fourth quarter of this year. Additionally Ardelyx is planning to begin a Phase 2b clinical trial in the fourth quarter of this year to evaluate the optimal dosing regimen for tenapanor for the treatment of hyperphosphatemia in dialysis patients.

"By regaining the worldwide rights to tenapanor, we now have a late-stage clinical asset that has demonstrated significant promise for the treatment of IBS-C and hyperphosphatemia, both of which are conditions where we believe tenapanor could potentially transform the treatment paradigm," said Mike Raab, President and Chief Executive Officer.

"Ardelyx can now accelerate the clinical development of tenapanor to meet the needs of two underserved patient populations. We are grateful for the substantial investment that AstraZeneca has made in the NHE3 program, and we have been fortunate to have them as a partner," Mr. Raab added.

In a separate press release, Ardelyx announced today a new product candidate, RDX022, for which it will be pursuing a 505b(2) regulatory pathway in the United States. Ardelyx is developing RDX022 for the treatment of elevated potassium, or hyperkalemia. Ardelyx expects to initiate clinical trials with RDX022 in mid-2015. Ardelyx also announced today that it has entered into an agreement to sell shares of common stock and warrants to purchase common stock for the aggregate gross proceeds of approximately $77.8 million in a private placement. Proceeds from the private placement will be used to develop both tenapanor and RDX022, two wholly-owned programs that are targeted to begin Phase 3 clinical trials in the fourth quarter 2015 and second half of 2016, respectively.

About the Termination Agreement

Ardelyx and AstraZeneca have executed a termination agreement under which Ardelyx regained all rights for all NHE3 inhibitors previously licensed to AstraZeneca, including tenapanor.

Under the terms of the termination agreement, Ardelyx has agreed to pay AstraZeneca certain amounts for the return of the rights, including $15 million up front, royalties equal to 10% of net sales of tenapanor by Ardelyx or a licensee, and 20% of non-royalty payments that Ardelyx receives from a new partner should it elect to license, or otherwise provide rights to develop and commercialize tenapanor, with all such amounts not to exceed $90 million. Ardelyx has also agreed to pay AstraZeneca $10 million in R&D costs and in consideration of the acceleration of the transfer of information, data and materials to Ardelyx. In addition, AstraZeneca is obligated to complete the manufacture of clinical trial material necessary for the Phase 3 clinical program in IBS-C patients, and Ardelyx has agreed to purchase the Phase 3 clinical trial material and other drug product inventory from AstraZeneca for up to $10 million.

Tenapanor's Clinical Development

Tenapanor is a minimally-absorbed small molecule inhibitor of NHE3, a transporter of sodium in the gastrointestinal tract. Orally administered tenapanor has been shown in clinical trials to reduce the intestinal absorption of both dietary sodium and phosphorus. A total of 14 clinical trials of tenapanor have been completed, and over 1,000 subjects have been administered tenapanor to date.

In October 2014, Ardelyx reported positive Phase 2b data for the use of tenapanor in treating patients with IBS-C. At the twice-daily 50mg dose of tenapanor, the study met its primary efficacy endpoint of an increase in the complete spontaneous bowel movement (CSBM) responder rate.

 

Pascal getting frustrated and lashing out against English board for not approving a cancer drug that is outrageous in cost! Getting a little testy there Frenchie??? Fire this dumb bastard now!
Come on Pfizer, go for a hostile bid!

http://www.fiercepharma.com/story/azs-soriot-lashes-out-uks-refusal-pay-first-class-cancer-drug/2015-06-03?utm_medium=rss&utm_source=feedly&utm_campaign=rss

 

Apparently the man thinks extending life by 11 months is a "cure."

How about if you put the person in a coma and they live 2 more years? Should the gubmint pay for that, knowing that 10 cents of every dollar goes into the paycheck of a brit ripping off the US taxpayers (who are now over 18T US in debt)?


Find a cure or stop trying to sell your overpriced shit here, asshole.

 

Poor old Pascal! Everything he touches turns to shit. Someone tell me why he is still here.

 

Off with his fucking head!!!!!!

 

Soriot is actually 100% right on this one.

Extending life by 11 months is a BIG deal in cancer treatment. This is not just tumor shrinkage, this is life extension. There are many cancer drugs already on the market that are being fully reimbursed that do much less for the cancer patient than that. And remember that is an average life extension, some patients may live for quite a while longer than 11 months, yet some other patients, for many reasons, may not respond well at all. If it is possible to figure out which patients are which beforehand than the ones that benefit most will have a tremendous asset to use in their fight against cancer. Cancer is a tough disease to halt and this is truly a remarkable result.

 

AZ 1st claims that AZ is for "Patient Health First."

Then AZ says, "We will not be undersold."

A difficult problem to lie your way out of. The truth is known.

 

AstraZeneca R&D boss Morrison leaves to head private drugmaker
Reuters
June 10, 2015 12:18 PM
By Ben Hirschler

LONDON, June 10 (Reuters) - AstraZeneca's chief medical officer and head of global late-stage drug development Briggs Morrison is to leave the company, creating a gap at the top of the group's research operations.

A spokeswoman said on Wednesday Morrison was departing to become chief executive of an unlisted venture capital-backed drugmaker in the United States, adding there had been no disagreement with other top managers at AstraZeneca.

"It is not appropriate for us to confirm the name of the company but it is an exciting new opportunity for him," she said.

Morrison, who joined AstraZeneca from Pfizer in 2012, has played a central role in the British drugmaker's bid to turn around its portfolio. He also helped defend the firm's independence in the face of a $118 billion takeover attempt by Pfizer last year.

Morrison will cease his current roles at the end of the week and leave AstraZeneca shortly after.

While the drugmaker seeks a successor, Chief Executive Pascal Soriot will take over responsibility for medicines development and Elisabeth Bjork will act as chief medical officer.

Soriot, who took over as CEO in October 2012, chose Morrison as one of his key drug research lieutenants, alongside Mene Pangalos, who heads early development work, and Bahija Jallal, leader of the group's MedImmune biotech unit.

AstraZeneca has won plaudits for recent progress with its pipeline of experimental drugs, especially in cancer, where it is investing heavily in the hot new field of immunotherapy.

Still, many industry analysts remain sceptical about its ability to lift sales to $45 billion by 2023 from $26 billion last year, a target set by Soriot when the company was fighting off Pfizer's attempted takeover last year.

It has suffered some setbacks, too, most recently when its partner Amgen pulled out of a psoriasis drug collaboration last month after suicidal thoughts were observed in patients taking the medicine.

AstraZeneca said it had not issued a formal statement about Morrison's exit because he was not a board member.

 

AstraZeneca R&D executive Morrison to lead cancer firm Syndax
Reuters
2 hours ago

LONDON, June 15 (Reuters) - AstraZeneca's outgoing chief medical officer and head of global late-stage drug development Briggs Morrison, whose departure from the British drugmaker was announced last week, is to head U.S. cancer firm Syndax Pharmaceuticals.

Syndax said on Monday that as its chief executive he would help take the privately owned company to the next level as it develops a drug called entinostat that modulates the immune system in the fight against tumours.

The U.S. company is already collaborating with Merck to evaluate entinostat in combination with Keytruda to treat lung cancer and melanoma.

Morrison's exit leaves a gap at the top of AstraZeneca's research operations.

 

Gout news: Not really great results for the Uloric combination study


Tue, Jun 16, 2015, 11:34 AM EDT
AstraZeneca Presents Phase III Data on Gout Drug Lesinurad
Analyst Blog
By Zacks Equity Research


AstraZeneca plc AZN presented data from a phase III study (CRYSTAL – Combination Treatment Study in Subjects with Tophaceous Gout with Lesinurad and Febuxostat) on its experimental gout candidate, lesinurad, at the annual congress of the European League Against Rheumatism.

The 12-month double-blind, multi-center, randomized, placebo-controlled study (n=324) was conducted to evaluate the efficacy and safety of a once daily dose of lesinurad (200 mg or 400 mg) in combination with Takeda Pharmaceuticals' TKPYY xanthine oxidase inhibitor, Uloric (febuxostat, 80 mg) compared to Uloric alone in gout patients who had at least one measurable tophus (deposits of uric acid crystals in joints and skin).

Results showed that a statistically significant higher number of patients on lesinurad 400 mg (76.1%) plus Uloric met the serum uric acid (sUA) level of <5.0 mg/dL at six months compared to Uloric alone (46.8%). On the other hand, lesinurad 200 mg plus Uloric failed to achieve that level at 6 months, thereby missing the primary endpoint of the study. However, patients with sUA ≥5.0 mg/dL when treated with lesinurad 200 mg plus Uloric resulted in more patients (44.1%) reaching the sUA target of <5.0 mg/dL compared to Uloric (23.5%) alone at month 6.

In addition, a post-hoc analysis of pooled data from the three phase III studies on lesinurad – CLEAR1, CLEAR2 and CRYSTAL – found that patients who achieved the lowest sUA levels, irrespective of treatment, experienced a greater reduction in gout flares and tophus area.

Currently, lesinurad (200 mg) is under review both in the U.S. (response expected in the fourth quarter of 2015) and the EU. We remind investors that lesinurad became a part of AstraZeneca’s gout portfolio through its acquisition of Ardea Biosciences in 2012. The acquisition also added another gout candidate, RDEA3170, to the company’s portfolio.

 

Who are you gonna believe? Stupid data or a smart AZ marketing exec?

AstraZeneca spells out key failures for gout drug in PhIII
June 15, 2015 | By John Carroll

AstraZeneca says that its experimental gout drug lesinurad failed to hit the primary biomarker target for the dose that it's now seeking regulatory approval for in the U.S. and Europe. And this latest Phase III--the last of a trio--continues to demonstrate that the pharma giant can't land evidence that the drug provides a clear benefit to patients in the time allotted for the study.

Physicians treat gout by going after lower serum uric acid (sUA) levels. And in that respect AstraZeneca ($AZN) says that it has abundant evidence of success. Testing a 200-mg and 400-mg dose, there has been data to support its argument that the drug works as billed. But the 400-mg dose is also linked to renal-related adverse events, which is why AstraZeneca is sticking with the 200-mg dose for its regulatory applications. And now it's detailing a failure on the key biomarker for the 200-mg patient group along with a lack of evidence that the drug can erase tophi, a manifestation of gout.

Investigators for the company reported that lesinurad, in combination with febuxostat, demonstrated greater sUA lowering to the target for tophaceous gout compared to febuxostat alone "at all months except at the time of the primary endpoint." The 56.6% vs. 46.8% scores did not represent a statistically significant outcome. There was a hit for a subgroup of subjects in the 200-mg arm. Lesinurad 400-mg in combination with febuxostat met the primary endpoint: 76.1% vs. 46.8%.

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AstraZeneca has consistently argued that it has the data to support the use of the drug to reduce sUA levels to the recommended treatment targets for treatment-resistant patients. The company trumpeted top-line results last summer, then unveiled the results of the first two studies in the fall, holding back CRYSTAL data for last weekend's meeting of the European League Against Rheumatism Annual Congress.

"Lesinurad is very effective" at lowering sUA, says Chris Storgard, a vice president for clinical research and development at AstraZeneca. That's the underlying cause of gout, he adds, and there have been consistent signs in late-stage studies that the drug works as billed. It's true, he adds, that the drug hasn't registered a statistically significant benefit in reducing the number of flares or erasing tophi, but that will take more time than the studies were designed to run. Investigators will now continue to track benefits for patients in an extension study of the big Phase III program, but Storgard says it's uncertain just how long it might be before efficacy can be fully understood.

Success for lesinurad is important for AstraZeneca's management team, which has been scrambling to prove that the pharma giant can effectively push new products through late-stage development to an approval after years of frustrating setbacks and reorganizations. Bernstein's Tim Anderson has projected potential 2020 sales for this drug at $582 million, making it a valuable contender in AstraZeneca's pipeline

 

It is another all time low for AZ. Another record for Frenchie, $63 per AZ share. The stockholders have to be putting pressure to change.

 

Smoking new venture:

AstraZeneca and Eolas Therapeutics enter into a worldwide license and partnership agreement on the Eolas Orexin-1 Receptor Antagonist program for smoking cessation and other indications (AZN) : The EORA program was awarded a Blueprint Neurotherapeutics grant from the National Institutes of Health NIH) for the development of the program from the preclinical stage through phase I clinical trials. The total deal potential is in excess of $145M. This includes upfront, clinical and regulatory milestone payments. Additionally, Eolas is eligible to receive royalties on commercial sales.

 

Is the AZ stock price back into the Fifties coming soon?

 

Give it time. Based on the current curve, we should hit the 50s in 6 weeks or less.

 

Before all of the Pfizer nonsense, this stock typically traded in the high forties to the mid fifties, and that was with Nexium, Crestor, Seroquel, Symbicort etc. bringing home the bacon The entire market has been super charged by massive investments into stock buybacks using near zero interest loans, rather than into their actual core businesses, so who knows where it will go now? AZ only recently halted their buybacks.

 

See, fire a few hundred numbers and stock goes up...problem solved. Need a better stock price remove a few hundred more numbers. Late winter or early spring I'm thinking.

 

Today's price rise is nearly all because of a reflexive bounce due to the notion that the Greeks "might pay" that has affected nearly all of the European companies.

By the way, the Greeks might sign an agreement, but in fact, they can not ever repay the debt, so this is just another kick the can exercise.

The real purpose of these agreements is so that the German banks and their sovereign debt and the IMF will not have to write down the loss due to the Greek default on their wobbly balance sheets, hence great rejoicing over any sign that they "might pay". Meanwhile, the Greeks, deep in a depression, are likely finding their suppers in the bins.