Major changes afoot at AstraZeneca

Major changes are afoot at AstraZeneca as it shakes up its research structure with new units, new names and big moves.

First up, we have José Baselga, who will run a newly formed cancer-focused unit. If that name sounds familiar, it’s because Baselga was the target of pieces from ProPublica and The New York Times a few months back, alleging he had been getting paid by pharma companies for work but had not been disclosing it properly.

He had been physician-in-chief at Memorial Sloan-Kettering, but was forced out in the fall over the allegations—something he later took full responsibility for, although this didn’t save his job.

In a letter to his former colleagues before being fired, obtained by The Cancer Letter, he said:

I apologize if any of the coverage and comments in the New York Times and ProPublica has caused any of my colleagues at MSK any embarrassment or professional or personal discomfort. I take responsibility for failing to make appropriate disclosures in scientific and medical journals and at professional meetings. I have already updated disclosures in medical journals and will continue to do so until the record is complete.

I want to be clear that while I may have been inconsistent in disclosing, the article does not question the validity of the research and the studies that were published.  I am committed to transparency and accountability in all of our dealings. That is my goal and I know I need to do better. I know you share my commitment to developing new treatments and medicines that will help our patients suffering from cancer.

I will be meeting with my team to discuss the article and will set up an opportunity to answer your questions and concerns.  I value your inputs and trust.

Now, the controversial scientist takes the helm at arguably AstraZeneca’s biggest unit, as it tries to rebuild its reputation and money-making power after a tough few years, with most of the bright spots coming out of its cancer trials (although not always).

And there’s more: Mene Pangalos, who was previously responsible for the company’s Innovative Medicines and Early Development Biotech Unit, will now take the helm at another new unit, the Research and Development unit for BioPharmaceuticals, which focuses on research for CV, renal and metabolism and respiratory—most of its work outside cancer.

Both men will report to AZ CEO Pascal Soriot. In a release, the U.K. Big Pharma said, “The units will share common basic biology and science platforms as well as product supply, manufacturing and IT infrastructure to improve efficiency. These resources will continue to be allocated on a Company-wide basis according to the overall therapy area considerations and strategy.”

Soriot added: “We are entering what we expect will be a period of sustained growth for years to come, which is why we have decided to more closely align our R&D and commercial operations. This new structure will support growth and sharpen the focus on our main therapy areas, speeding up decisions and making us more productive in our mission to bring innovative medicines to patients.

“In line with these changes, I am delighted to welcome José to AstraZeneca. An outstanding scientific leader in Oncology, José’s research and clinical achievements have led to the development of several innovative medicines, and he is an international thought leader in cancer care and clinical research. José’s expertise adds further scientific and leadership excellence to our already strong team and will help us to continue building a world-class R&D unit for Oncology.”

Baselga added: “After more than 30 years helping develop medicines in this area, it is a true privilege to now have the opportunity to work with the tremendous Oncology expertise at AstraZeneca. Bringing the discovery through to late-stage development chain into one unit will make the process more agile and accelerate our work to bring transformative medicines to patients. This really is a dream job.”

https://www.fiercebiotech.com/biotech/baselga-takes-helm-astrazeneca-s-cancer-r-d-as-pharma-rings-new-year-big-changes

Lilly CEO says will leave CAR-T therapies to others

Eli Lilly (LLY) CEO Dave Ricks said that the company will leave CAR-T therapies for cancer and gene therapies for rare diseases to others, as the company seeks deals to enhance its pipeline of future treatments, Reuters reports. “The data is amazing, but practically, it’s not reaching many people,” Ricks said of CAR-T therapy in an interview with Reuters. The comments come after the company announced an $8B purchase of Loxo Oncology (LOXO) this week, the report says

https://thefly.com/landingPageNews.php?id=2847726

Want to buy Clovis? Step up. ‘Everybody knows where to find me,’ CEO says

Shortly after GlaxoSmithKline bought PARP-inhibitor innovator Tesaro for $5.1 billion in early December, analysts started buzzing about the likelihood that Clovis Oncology would be the next PARP player to get scooped up at a high premium.

Now Clovis CEO Patrick Mahaffy is making it clear he’s ready to deal.

“Everybody knows where to find me and every company in this industry is for sale,” he said during a Q&A session after his presentation at the J.P. Morgan Healthcare Conference. “We just are. It’s all a question of whether somebody shows up.”

Mahaffy prefaced the comment by saying he didn’t want to “sound snarky.” But snarkiness aside, Mahaffy’s response to the ongoing buyout speculation was certainly timely. The conference kicked off with the news that Eli Lilly plans to buy Loxo Oncology for $8 billion, and that deal came just four days after the year’s first megamerger: Bristol-Myers Squibb’s planned purchase of Celgene for $74 billion.

Both of those marriages demonstrated that not only has the long-predicted M&A boom in biopharma arrived, but that oncology assets are among the most highly valued in the industry. Analysts predict that M&A will be driven by the combination of ready cash and recently depressed valuations of hot takeover targets—Clovis’ share price, for example, plunged from over $46 to about $18 in the six months leading up to J.P. Morgan.

Fact is, Clovis could use a big partner to help market its main asset, ovarian cancer therapy Rubraca. The company has struggled to set the drug apart from its PARP competitors, which include AstraZeneca and Merck’s Lynparza. Much of the loss of value in Clovis’ stock came after its third-quarter report, when it revealed that sales of Rubraca had been just $22.8 million—much less than the $31.3 million analysts had expected.

During his presentation at J.P. Morgan, Mahaffy told analysts to expect Rubraca to bring in at least $30.3 million in sales in the fourth quarter and $95.3 million for the year. Still, significant marketing challenges remain.

Despite clinical trials showing impressive improvements in progression-free survival with Rubraca, key opinion leaders still don’t perceive a significant difference between the product and its rivals, Mahaffy said: “It’s been hard, even with the great PFS we have, to have differentiation that would drive greater adoption of Rubraca.”

Mahaffy described a new marketing plan Clovis is launching called “assess, confirm, treat.” The idea is to move beyond progression-free survival and instead focus on the fact that Rubraca produces additional tumor shrinkage over time, he explained. “The basic idea is to create a call-to-action in the maintenance setting in a way that is self-evident in the treatment setting, and to create a sense of urgency” among physicians who might have taken a watch-and-wait approach rather than keeping patients on a PARP inhibitor, he said.

Still, Mahaffy conceded that being a small player puts Clovis at a disadvantage in the market to products like Tesaro’s Zejula, which is now backed by the GSK development and marketing machine. Tesaro has long been a “very aggressive, very capable marketer,” he said, noting that it had been spending twice as much on sales and administrative functions than Clovis does.

Over the long run, with GSK’s resources, “if they choose to, they can put resources into a lot more clinical development programs than we can,” Mahaffy said, which could lead to additional approvals for Zejula “and therefore advantages.”

It isn’t just the analysts at J.P. Morgan who have been pressing Mahaffy to consider a sale. Shareholder Armistice Capital has been boosting its ownership stake in Clovis and now holds 9.8% of the company. In a filing to the Securities and Exchange Commission late last year, Armistice said it’s weighing a number of actions, one of which might be “recommending business development transactions including a sale,” it said.

One major selling point for Clovis could be the potential approval of Rubraca in prostate cancer. Clovis nabbed breakthrough status from the FDA in that indication, and Mahaffy confirmed during J.P. Morgan that the company hopes to file for that approval by the end of this year. Clovis is expected to be ahead of its rivals in the market for PARP inhibitors to treat prostate cancer.

An acquisition of Clovis would be better for shareholders than, say, an equity financing or something else that could be dilutive, one analyst suggested during the Q&A session at J.P. Morgan. Mahaffy said the company isn’t considering an equity offering.

As for the acquisition buzz, he said, “the reality is we’re open to it. … In the meantime, we’re going to create value.”

https://www.fiercepharma.com/pharma/will-clovis-be-acquired-everybody-knows-where-to-find-me-ceo-says-at-jpm

Orchard’s 2019: Pipeline progress, start on $90M Cal. manufacturing site

Orchard Therapeutics started 2018 with two clinical-stage assets and a preclinical pipeline that was, in CEO Mark Rothera’s words, “not that large.” Now, after picking upGlaxoSmithKline’s rare disease gene therapy unit and becoming a commercial-stage company, Orchard is looking to bring its treatment for “bubble boy syndrome” to the U.S. and ramp up its clinical work.

Orchard acquired the GSK assets in exchange for a 19.9% stake in Orchard and undisclosed milestones and royalties. These included the EMA-approved Strimvelis, which treats ADA-SCID, a rare genetic disorder that causes immunodeficiency, as well as late-stage candidates for metachromatic leukodystrophy (MLD) and Wiskott-Aldrich syndrome (WAS).

The company, based in Boston and London, now has five clinical-stage gene therapies and 10 preclinical programs.

“I would say we have the world-leading gene therapy pipeline today … partly because it’s very advanced, but also very deep,” Rothera said at the J.P. Morgan Healthcare Conference. The company plans regulatory filings for its three leading clinical programs within the next three years and will move one of its preclinical assets into the clinic in 2019, he said.

And with $375 million total raised, Orchard has a big year ahead. Of course, a key use of the cash will be clinical and manufacturing work, but a good chunk of it—about $90 million, Rothera reckons—will fund Orchard’s 150,000-square-foot manufacturing site in Fremont, California.

The company has already signed on the contract manufacturing organizations (CMOs) for the launch of its ADA-SCID, MLD and WAS treatments, but is looking to “take charge” of its “own destiny.” The site won’t be running until 2021, and Orchard plans to continue working with CMOs to make its treatments, but the combination of having its own facility as well as manufacturing partners “provides some redundancy, that you want a bit of,” Rothera said.

With Strimvelis already marketed in Europe, Orchard is focusing on getting OTL-101, its ACA-SCID treatment, to patients in the U.S., where there is no gene therapy for the disease. It’s planning to file for FDA approval in 2020. Eventually, OTL-101 will supplant Strimvelis, which is approved for use at one treatment center in Milan. OTL-101, like the rest of Orchard’s pipeline, uses a newer, lentiviral vector, and unlike Strimvelis can be cryopreserved.

“It’s not patients who will do the traveling, it’s the cells,” Rothera said.

In addition to requiring travel, Strimvelis, which was developed as a fresh cell product, has a small window of time to extract a patient’s stem cells, insert a working copy of the disease-causing gene and put the cells back into the patient—about six hours. This means quality control can be difficult.

“[The new technology] allows potentially weeks to make sure of the right number of cells, viability, sterility, the right [vector copy number.] When you give it back to the patient, the chance of it working looks much, much clearer,” Rothera said.

After bringing gene therapy to ADA-SCID patients in the U.S., Orchard will look to Europe and other parts of the world.

“At that point, patients will have a choice [between Strimvelis and OTL-101,” Rothera said. “I’m sure which way that’s going to go.”

https://www.fiercebiotech.com/biotech/orchard-therapeutics-2019-pipeline-progress-breaking-ground-its-90m-manufacturing-site

hVIVO preps phase 3 for ‘universal’ flu vaccine

U.K. biotech hVIVO is on course to start a phase 3 program for a flu vaccine that doesn’t need to have its composition tweaked every year—and as a result has been tipped by some analysts as a potential blockbuster.

hVIVO’s AIM-listed shares surged after the company revealed additional results for its phase 2b trial of FLU-v showing that it was able to significantly reduce mild to moderate influenza disease (MMID) compared to placebo, the study’s primary endpoint.

Last year, the National Institute of Allergy and Infectious Diseases (NIAID)—which is running the study—said that the vaccine had hit secondary targets including a reduction in flu symptoms, but there was a delay in getting the primary readout because patient samples needed further testing to confirm influenza infection.

A less sensitive assay was used initially which only showed a trend toward significance on the MMID outcome measure, so the NIAID retested samples using an improved assay that “identified more cases of influenza infection than had originally been determined, resulting in the achievement of statistical significance,” said hVIVO Executive Chairman Trevor Phillips, Ph.D., in a statement(PDF).

The trial represents the first time that a “universal” flu vaccine has been shown to reduce symptoms as well as stimulate an immunological response, according to Phillips.

In addition to sidestepping the need for the annual scramble to identify the prevailing influenza strains for inclusion in traditional flu vaccines, Flu-V is also designed to minimize the virus’ impact by reducing symptoms, potentially relegating it to a much milder disease.

The synthetic polypeptide vaccine is also less likely to result in a mismatch in flu strains, which can leave vulnerable patients at risk of infection even if they receive a shot. There is also hope that it could confer protection against emerging unexpected strains that can cause global epidemics, such as the H1N1 outbreak in 2009.

Moving Flu-V to phase 3 will be a big deal for hVIVO, which focuses mainly on providing viral challenge trial services to other pharma companies rather than developing its own products. It has set up a joint venture with fellow U.K. company SEEK Group—called Imutex—to develop the flu vaccine and has a 49% stake in that company.

Universal flu vaccine R&D programs are also being run by other groups, including Israel’s BiondVax Pharmaceuticals, which reported phase 3 results for its M-001 candidate at the World Vaccine Congress in San Diego last November.

https://www.fiercebiotech.com/biotech/hvivo-preps-phase-3-for-universal-flu-vaccine

JP Morgan Day 4: Basilea

David Veitch, CEO of Basilea Pharmaceutica (BSLN), gave a “whistle-stop” overview of the
company, including plans for the portfolio of two commercial stage assets and three oncology
products in the pipeline, as well as the financial position of the company going into 2019. With a
stronger than expected preliminary revenue in 2018, the company is in a good financial position
to focus on their goals of expanding the oncology and anti-infectives pipeline, including multiple
clinical oncology products and ceftobiprole – a fifth generation cephalosporin.
The company’s strong 2018 performance was mainly driven by the continued uptake of
Cresemba and Zevtera. Cresemba’s in-market sales amounted to $145m as of Q3 2018, and
Basilea intends on launching Cresemba in 40 additional markets over the next three years. With
clinical studies demonstrating non-inferiority of Cresemba to the standard of treatment,
voriconazole, while showing a superior safety profile and broader action spectrum, the company
hopes to increase the US market share of Cresemba in the upcoming years. The increase in
market share is expected to be further powered by the ECIL-6 guidance for the use of Cresemba
in first-line treatment of aspergillosis in leukemia and hematopoietic stem cell transplant patients
due to its safety profile. Zevtera, which is indicated for use in hospital- and community-acquired
pneumonia, is marketed in the major EU markets, Canada, and several other markets in South
America and Asia. In its anti-infective pipeline, the company plans to gain market approval for
ceftobiprole in 2022 for the treatment of acute bacterial skin and skin structure infections, as well
as Staphylococcus aureus bacteraemia, following the completion of two ongoing supportive
Phase III studies in the US.
In the presentation of the oncology portfolio, the CEO mentioned three main agents: BAL10153
for recurrent or progressive glioblastoma and platinum-resistant ovarian cancer, BAL3833 for
patients with solid tumors including metastatic melanoma, and an in-licensed pan-FGFR kinase
inhibitor, derazantinib, for intrahepatic cholangiocarcinoma. Derazantinib, which is Basilea’s lead
oncology compound, is currently in a registrational Phase II study with interim results expected in
H1 2019. The CEO disclosed that the interim analysis of the Phase II study shows encouraging
results, which mirrors the achievements seen from a Phase I study, including an increased
objective response rate and improved disease control rate.
Veitch briefly mentioned BAL10153 and BAL3833. He highlighted that BAL10153, with its ability
to penetrate the blood brain barrier, is being investigated in three ongoing studies in patients
with newly diagnosed and recurrent glioblastoma. Data from two of the studies is expected in
2019. BAL3833 has completed one Phase I study to date, but with the maximum tolerated dose
not identified during the trial, the company will further explore the use of the drug in solid tumor
treatment.

http://images.intelligence.informa.com/Web/InformaUKLimited/%7Ba9dcc568-c28c-450e-a678-60ab0dbb2304%7D_JP_Morgan_2019_-_Day_4.pdf

JP Morgan Day 4: Arena Pharmaceutical

Arena Pharmaceutical’s (ARNA) presentation outlined their four products, however, unsurprisingly
the main focus was on etrasimod and olorinab. They began the presentation outlining their bestin-class S1P receptor modulator Etrasimod for the treatment of ulcerative colitis (UC) and Chron’s
disease (CD). Officials claimed that there is a $3-4b market opportunity in UC and CD with
etrasimod. They also pointed out that although some think this is an already crowded market it is
estimated to be worth $23b in 2026 as the prevalence of the disease is continuously increasing.
The CDC NHIS household survey indicate that prevalence could reach 3.1m in the EU.
Additionally, officials explained that only 40% of responders on biologics achieve remission at
1year. Etrasimod recently released positive data from a Phase II OASIS open-label extension
study, which demonstrated that 39% of patients achieved long-term clinical remission at both 12
and 46 weeks. Arena further summarised recently released data, which shows that etrasimod has
rapid onset and offset action, competitive efficacy in UC and demonstrated a consistent
reduction in lymphocytes with an improved clinical response. They explained that etrasimod’s
highly selective properties enable it to have a good safety and tolerability profile with no SAEs
and most significantly there were no cases of sinoatrial arrest, which has been observed in
competing compounds. Officials also highlighted the response of 100 GI physicians in a
quantitative conjoint study, which indicated that etrasimod was likely to be preferred in the
future compared to JAK inhibitors and ozanimod. Arena stated that a Phase III UC study and
Phase II/III CD study will be initiated in 2019. They said the Phase III study, which is an expedited
trial design, aims to drive rapid enrollment through patient referrals and a high-touch
engagement using their internal field-based team.
Arena then switched its focus on exploring etrasimod for atopic dermatitis, which has a
prevalence of 22m in the US. They said that there is a severe impact on quality of life with 86% of
patients not satisfied with current treatment options. Officials reiterated that early clinical results
were positive in reducing wounds caused by pyoderma gangrenosum. A Phase II trial is expected
to initiate in 2019.
In addition, officials highlighted old data from olorinab for treatment of IBS and IBD. They noted
that olorinab was a non-opioid that could address GI pain, which is a current unmet need. Arena
summarised successful results from Phase IIa, which showed that olorinab significantly reduced
abdominal pain over 8 weeks in patients with Chron’s disease. They stated that olorinab was a
$1-3b opportunity and confirmed plans to initiate Phase IIb IBS and IBD studies in 2019.
Officials very briefly mentioned ralinepag, which is a selective prostacyclin receptor agonist for
pulmonary arterial hypertension. They highlighted their global license agreement with United
Therapeutics who will receive exclusive worldwide rights. This strengthens their strategic position
to advance etrasimod and olorinab.
Arena concluded the presentation with a summary of APD418 for decompensated heart failure.
They confirmed that this therapy improved cardiac function without any hemodynamic changes
in animals, which is an advantage over other inotrope therapies such as Dobutamine. Officials
stated that they are preparing an IND submission for 2019.

http://images.intelligence.informa.com/Web/InformaUKLimited/%7Ba9dcc568-c28c-450e-a678-60ab0dbb2304%7D_JP_Morgan_2019_-_Day_4.pdf