Pfizer Cuts Neuroscience Development, Then Adds $150M to Neuroscience JVs

In late January, Pfizer Inc. abandoned its research and development of new neuroscience programs. Along with the news came 300 job cuts. It was terminating eight different projects. Two were in Phase II while six others were in Phase I. The two Phase II projects were PF-06372865 for epilepsy and PF-06649751 for Parkinson’s disease. Four of the Phase I projected targeted Alzheimer’s disease. The other two Phase I candidates were for a cognitive disorder and schizophrenia.

Now Pfizer is throwing an additional $600 million into its venture capital fund, with a quarter of it earmarked for neuroscience research investments. It will bring Pfizer Ventures’ total funding to over $1 billion. Business Insider notes, “Several drugmakers, including Pfizer, have cut back on neuroscience research after a string of costly trials yielded disappointing results, with some of them betting on startups that are focusing on such areas. Pfizer has already invested in six neuroscience companies and, alongside drugmakers such as GlaxoSmithKline and Eli Lilly, is part of the Dementia Discovery Fund, which has raised more than $190 million since its 2015 launch.”

Those six companies include Aquinnah, Autifony, Cortexyme, MindImmune, MISSION, and Neuronetics.

Glenn Larsen, co-founder, president and chief executive officer of Aquinnah, said in a statement, “Pfizer’s investment in Aquinnah is helping advance two exciting Stress Granule neurodegenerative programs in Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease. By being located in LabCentral within the Pfizer building in Kendall Square and through our joint efforts, Aquinnah has access to a leading group of scientific advisors, as well as state of the art technology facilities.”

About $150 million will be invested in early-stage neuroscience companies, with a particular focus on neurodegeneration, neuroinflammation and neuro-metabolic disorders.

Pfizer’s vice president, Worldwide Business Development and senior managing partner of Pfizer Ventures, Barbara Dalton, said in a statement, “By expanding Pfizer’s venture capital efforts under Pfizer Ventures, we hope to extend both the breadth and depth of Pfizer’s support for the development of cutting-edge science from concept to products. Building on our existing investments and proven track-record, we will look to identify and invest in emerging companies that are advancing compounds and technologies with the hope of delivering life-changing therapies to patients in need.”

In addition to the additional funding, Pfizer is expanding the Pfizer Ventures team. It will be still led by Dalton with Elaine Jones and Bill Burkoth. But Denis Patrick, vice president, Pfizer Worldwide Research and Development and managing partner of Pfizer Ventures, Laszlo Kiss, Margin McLoughlin, Chris O’Donnell and Nikola Trbovic will also be joining the group. It consolidates R&D Innovate, Pfizer’s R&D equity investment vehicle with Pfizer Venture Investments.

“By changing the way we invest in neuroscience, we hope to support an energized community of biotech entrepreneurs who are progressing the understanding of the molecular mechanisms of neurologic diseases and help advance potential treatments for people with neurological conditions,” Denis Patrick said in a statement.

About 80 percent of Pfizer Ventures investments will be made in the U.S. It will also commit up to $10 million when it first invests.

https://bit.ly/2sMZiKO

Genentech and Microbiotica Ink Multi-Year Collaboration Deal

Genentech, a Roche company, and Microbiotica, in Cambridge, England, signed a multi-year strategic collaboration to discover, develop and commercialize biomarkers, targets and drugs for inflammatory bowel disease (IBD).

Microbiotica was spun out of the Wellcome Sanger Institute 18 months ago, and focuses on microbiome-based therapeutics. Under the deal, Microbiotica will use its precision metagenomics microbiome platform to analyze samples from clinical trials of Genentech’s IBD drugs. The goal is to identify microbiome biomarker signatures of drug response, with hopes of finding novel IBD drug targets and potentially develop live bacterial therapeutic products.

This is a relatively new area of drug development and health, the study of how different bacterial strains of bacteria living in the human body effect various disease states.

Genentech is paying Microbiotica an undisclosed upfront payment. It will be eligible for various milestone payments up to $534 million. Also, Microbiotica will be eligible to receive royalties on sales of specific products that might come out of the collaboration. Genentech also has the option to license assets the company might develop out of the collaboration.

“This brings together a world-class pipeline of investigational IBD medicines from Genentech with the world-class microbiome capability of Microbiotica,” said Mike Romanos, chief executive officer of Microbiotica, in a statement. “We are excited by the opportunity to work with Genentech scientists in order to bring precision metagenomics into the clinical arena for the first time, enabling us to develop biomarkers and medicines for the benefit of patients.”

In early May, Genentech signed a strategic drug discovery collaboration with Lodo Therapeutics, a New York City-based company. That deal could potentially be worth more than $1 billion. Under the terms of that deal, Genentech will use Lodo’s proprietary genome mining and biosynthetic cluster assembly platform to identify potential therapeutics against multiple disease targets. Again, there was an undisclosed upfront payment, but Lodo is eligible for various milestone payments that could hit $969 million. Lodo will also be eligible for tiered royalties.

Lodo’s platform identifies and produces bioactive natural products directly from the microbial DNA sequence information contained in dirt. The information in the organisms’ genomes drive the company’s discovery programs. It was founded on the scientific work of Sean Brady, head of The Rockefeller University’s Laboratory of Genetically Encoded Small Molecules.

These two deals indicate a strong interest on the part of Genentech in developing new drugs based on microbiomes. James Sabry, senior vice president and global head of Genentech Partnering said in a statement, “We believe the microbiome represents a new paradigm in biomedicine, both for understanding drug response and as a novel therapeutic modality. We have chosen to collaborate with Microbiotica because of its high-quality science and look forward to working together to potentially bring new medicines to people suffering from IBD.”

Overall, there’s quite a bit of movement—no pun intended—in this area of research. In April 2018, Ferring Pharmaceuticals, headquartered in Saint-Prex, Switzerland, acquired Roseville, Minnesota’s Rebiotix. Ferring focuses on reproductive medicine and women’s health, with specialty areas within gastroenterology and urology. Rebotix is a late-stage clinical microbiome company.

In April 2017, Takeda Pharmaceutical Company signed a global collaboration deal with Somerville, Massachusetts-based Finch Therapeutics. They will jointly develop FIN-524, a live biotherapeutic product made up of cultured bacterial strains that have been associated with favorable clinical outcomes in research of microbiota transplantations in IBD.

And in April 2018, Synlogic, based in Cambridge, Massachusetts, dosed its first patient in its Phase Ib/IIa clinical trial of SYNB1020 for hyperammonemia, a metabolic disorder characterized by excess ammonia in the blood. SYNB1020 is a Synthetic Biotic, taken orally. It can act in the gut to compensate for the dysfunctional metabolic pathway. The company’s approach is to program naturally-occurring microbes using synthetic biology tools. The engineered microbiome then effects the body’s metabolic dysregulation.
Although these examples all focus on bowel diseases, there is quite a bit of work looking at how the microbiota affect every organ system and disease state.

https://bit.ly/2sBMlUW

What’s with Longevity Firm Unity Biotechnology and its $700M Valuation?

Early biotech company valuations are a type of voodoo made up of interesting ideas, talented management, investor enthusiasm and wishful thinking. How to explain UNITY Biotechnology,which wants to help you stay young until you die? The company has raised $222 million in venture capital, raised $85 million in an initial public offering (IPO) in May, and has a value of $700 million. All without having a product to sell.

Unity Biotechnology’s focus is on killing senescent cells. These cells are essentially aging cells that aren’t quite dead, but aren’t actually doing anything anymore, and they build up in the body and are part of what makes people feel old—related to achy joints, diminished eyesight and some diseases of aging, potentially Alzheimer’s. The company believes that if you can kill those senescent cells, you can eliminate many of the symptoms of aging.

“Like, how awesome would it be?” said Nathaniel “Ned” David, the co-founder and president of the company, to Forbes. “The problem is you have to take the first baby step to demonstrate it’s possible. That’s what chapter one is: demonstrate in a human being that the elimination of senescent cells takes a heretofore inescapable aspect of aging and can either halt it or reverse it.”

“Just that,” responds the company’s chief executive officer and chairman, Keith Leonard. “It’s easier to talk to the Food & Drug Administration about treatment of a disease once it’s diagnosed than it is to work really early and prevent disease. But [prevention] is what we’d love to get to.”

At the moment, the company’s pipeline is all early stage. UBX0101 is close to Phase I for osteoarthritis. Its UBX1967 is in lead optimization for diabetic retinopathy and diabetic macular edema, glaucoma, and age-related macular degeneration. It also has other programs in pulmonary diseases, cognition, and kidney disease, all in the preclinical stages. UBX0101 is currently recruiting patients for a Phase I trial.

UBX0101 is described as “a potent senolytic small molecule inhibitor of the MDM2/p53 protein interaction. Disruption of this protein interaction can trigger the elimination of senescent cells.”

UBX1967 is for diseases of the eye and is a senolytic small molecule inhibitor of specific members of the Bcl-2 family of apoptosis regulatory proteins. The company notes, “Senescent cells utilize pro-survival mechanisms to remain viable and rely on specific Bcl-2 protein family members to persist and accumulate in tissues.” The company plans to submit its IND application and begin a Phase I trial in the second half of 2019.

Ned David co-founded Unity in 2011 because, he said, it was “simply the coolest biology he had ever seen.” Prior to co-founding the company, he co-founded four other biotech companies that in total have raised over $1.5 billion in financing. These include Syrrx, which was acquired by Takeda, Achaogen (AKAO), Kythera Biopharmaceuticals, later acquired by Allergan, and Sapphire Energy.

Kristina Burow, managing director at Arch Venture Partners, who has invested in four of David’s companies, told Forbes, “He’s probably the best person in the world at finding great academic science and shaping it into a fundable story and a sellable business plan.”

There may be two other factors involved as well. First, the timing just may be right for research into longevity—science has a much deeper understanding of aging based on things like senescent cells and telomere shortening—a function of cell division that places a limit on the number of times a cell can divide. And secondly, a lot of investors, especially of the billionaire-variety, are aging.

It was recently noted that a number of billionaires who are fifty years or older in age, have been investing in health care and longevity-related startups companies. That includes Bill Gates, 62, Michael Bloomberg, 76, Richard Branson, 67, Tim Disney, 57, Andrew Russel, 56, Jeff Bezos,65, Peter Thiel, 50.

Another factor, not really related to age, is that there are a number of people who have created enormous amounts of wealth, often via tech companies, and longevity research just seems like a good idea whose time has come. Which may be why Mark Zuckerberg, Facebook founder and his wife, physician Priscilla Chan, have invested $3 billion toward basic research over the next 10 years. Both of them are 33 years old. And Bill Marris, who is 42, the founder and former chief executive officer of GV (Google Ventures), invested and founded Calico, a Google/Alphabet company, whose focus is aging and related diseases.

It’s possible that betting on a potential fountain of youth is just a good investment.

https://bit.ly/2Jm3ZlQ

Biogen Pays Alkermes $50 Million Milestone for MS Drug

Alkermes, headquartered in Dublin, Ireland, received a $50 million milestone payment from Cambridge, Massachusetts-based Biogen. The payment occurred after Biogen reviewed preliminary gastrointestinal tolerability data from an ongoing Phase III clinical trial of BIIB098 (diroximel fumarate) for relapsing forms of multiple sclerosis (MS).

Under the terms of their agreement, Biogen has exclusive commercialization rights to the drug. Alkermes is eligible for a royalty in the mid-teens on worldwide net sales, should the drug be approved. Alkermes is also eligible for a $150 million milestone payment if the U.S. Food and Drug Administration (FDA) approves the drug, on or before December 31, 2021.

Alkermes is expected to submit a New Drug Application (NDA) for the drug to the FDA in the last quarter of this year.

The original deal was signed in November 2017, when the drug was dubbed ALKS 8700. It is a novel, oral, monomethyl fumarate (MMF) small drug molecule. Biogen reimbursed Alkermes for half of the 2017 development costs and paid Alkermes an upfront payment of $28 million, which represented Biogen’s share of development expenses already incurred that year.

Starting at the beginning of 2018, Biogen handled all development expenses related to the drug. Alkermes is eligible for milestone payments up to $200 million—which is already received $50 million. Alkermes will handle regulatory applications with the FDA, and Biogen will handle commercial activities for the drug, if approved.

The primary components of the EVOLVE-MS (Endeavoring to Advance Treatment for Patients Living with Multiple Sclerosis) clinical program of ALKS 8700/BIIB098 include a two-year safety trial and pharmacokinetic bridging studies comparing the drug and Tecfidera. The program also includes an elective head-to-head study comparing the GI tolerability of the drug and Tecfidera.

“The clinical data generated from this program underscore the potential value of BIIB098 for patients with multiple sclerosis,” said Richard Pops, Alkermes’ chief executive officer, in a statement. “Our focus remains on completing the registration requirements and preparing the BIIB098 NDA for submission in the fourth quarter of 2018, as we advance this important potential new therapeutic option for patients with MS.”

Alkermes is a busy company, with a market cap of $7.19 billion. It markets Aristada for schizophrenia, Vivitrol for alcohol and opioid dependence, Risperdal Consta for schizophrenia and bipolar I disorder, Invega Sustenna for schizophrenia and schizoaffective disorder, Xeplion, Invega Trinza, and Trevicta for schizophrenia, Ampyria/Fampyra to enhance walking in MS patients, and Bydureon for type 2 diabetes. It currently has ALKS 5461 in Phase III trials for depressive disorder, ALKS 3831 in Phase III for schizophrenia, ALKS 8700 for MS, and ALKS 6428 in Phase III to assist physicians transition patients from physical dependent on opioids. Its Aripiprazole lauroxil recently finished a Phase I trial for schizophrenia, and ALKS 4230 is in Phase I clinical trials for cancer immunotherapy.

Biogen, a leader in MS treatments, announced yesterday that it had expanded its strategic collaboration with Ionis Pharmaceuticals to discover and develop novel antisense drugs for neurological diseases. Biogen paid Ionis $1 billion in cash, including $625 million for 11,501,153 shares of Ionis common stock at a price of $54.34 per share and a $375 million upfront payment. The expansion was originally announced on April 20, 2018. The companies expect to advance programs for diseases including dementia, neuromuscular diseases, movement disorders, ophthalmology, diseases of the inner ear, and neuropsychiatry.

https://bit.ly/2xPHtAx

Cancer Research, Medical Records Targeted by Amazon Mystery Initiative

The secret group within Amazon working on a series of bold projects is starting to become a little less secret. Several news reports in recent days have speculated on the purpose and structure of the new group within the company traditionally known for e-commerce, consumer devices and web services.

On Tuesday, MSNBC cracked the story by reporting that the group, known as Grand Challenge, was being led by Google Glass creator Babak Parviz. According to an internal chart, Grand Challenge is part of Amazon Web Services (AWS) and Parviz reports directly to AWS CEO Andy Jassy.

“Similar to Alphabet’s experimental research lab, X (formerly Google X), Grand Challenge is a research team set up to explore ambitious new ventures that can eventually expand Amazon’s already wide footprint,’ MSNBC reported.

BioSpace readers will be particularly interested to know about two possible areas of focus — cancer research and medical records.

Cancer research to be supported by AI application

According to those familiar with the project, Parviz and his team are working with Fred Hutchinson Cancer Research Center in Seattle to apply machine learning in ways that can help prevent and cure cancers.

Machine learning is an application of artificial intelligence (AI) that provides systems the ability to automatically learn and improve from experience without being explicitly programmed. Machine learning focuses on the development of computer programs that can access data and use it to learn for themselves.

The story has also been covered by GeekWire. “We have several projects underway with a few of our tech neighbors including Microsoft, Amazon and Tableau,” said a Fred Hutchinson spokesperson. “Given the early stages, we don’t have any specific Amazon Web Services projects to preview but hopefully later this year,” GeekWire reported.

Patient data analysis to improve accuracy of medical records

In January, a press release on BioSpace seemed to foreshadow Amazon’s entry into the medical records field. At the time, they were looking for a professional who can “own and operate” the security and compliance aspects of a new initiative. The job posting also required the candidate to ensure that the new initiative meets HIPAA business associate agreement requirements, meaning Amazon intends to work with outside partners that manage personal health information.

That initiative has been internally dubbed Hera, MSNBC reported. In development for at least three years, Hera involves taking unstructured data from electronic medical records to identify an incorrect code or the misdiagnosis of a patient. The technology captures patient data that a physician may miss. This can help remove inaccuracies for insurers, resulting in greater efficiencies and more accurate assessment of a population’s risk.

According to two people familiar with the effort, Grand Challenge is already starting to pitch Hera to commercial health insurance companies.

https://bit.ly/2HpV55j

Axovant Licenses Gene Therapy for Parkinson’s from Oxford BioMedica

Axovant Sciences, one of Vivek Ramaswamy’s biotech startups best known for its spectacular flameout over its Alzheimer’s drug in September 2017, is taking another shot, this time at Parkinson’s disease.

The company announced it has licensed exclusive worldwide rights to OXB-102, now dubbed AXO-Lenti-PD, from Oxford BioMedica The compound is an investigational gene therapy for Parkinson’s disease. It is designed to deliver three genes that encode a set of enzymes required for dopamine synthesis in the brain.

Oxford BioMedica focuses on lentiviral vector product development and manufacturing. It will continue as the clinical and commercial manufacturer of AXO-Lenti-PD.

Axovant says it plans to launch a Phase I/II dose-escalation trial of AXO-Lenti-PD in patients with advanced Parkinson’s disease by the end of 2018.

Part of Ramaswamy’s business strategy, aside from convincing investors to heavily invest in his companies, is to acquire cast-off drugs from other companies for bargain-bin prices. The key example is intepirdine, which is the Alzheimer’s drug that failed in a Phase III trial. Ramaswamy and Axovant bought the drug from GlaxoSmithKline for $5 million. It had shown a favorable safety and tolerability profile, and in a Phase IIb trial, showed immediate and sustained efficacy over placebo. But it had been abandoned by GSK after four clinical trials.

This appears to be something of a strategic pivot—although a very risky one—for the company. Axovant is paying an upfront payment of $30 million in cash, $5 million which will be applied as a credit towards the process development work and clinical supply. Oxford BioMedia will be eligible for various milestone payments that could exceed $812 million, as well as tiered royalties on net sales of the product if approved.

In addition, Roivant, Ramswamy’s parent company, will buy $25 million of Axovant common shares, which will support the clinical development of AXO-Lenti-PD.

The company is also shaking up its executive team, which has been undergoing a shakeup since September anyway. Last summer David Hung, former founder and chief executive officer of Medivation had taken on the chief executive role. But he left the company shortly after the Alzheimer’s failure. Pavan Cheruvu took over in February 2018.

Part of today’s announcement included that Fraser Wright will join the company as chief technology officer. He is the co-founder and former chief technology officer of Spark Therapeutics.

Cheruvu said in a statement, “Axovant remains committed to developing innovative treatments for serious neurodegenerative conditions such as Parkinson’s disease, and we are excited to partner with Oxford BioMedica, a recognized global leader in cell and gene therapy. We are also pleased to welcome Fraser to our leadership team.”

It’s anyone’s guess as to whether this shift will be successful. Parkinson’s is a slightly less volatile arena than Alzheimer’s, but it’s no picnic, either. As STAT points out, “If you bet $100 on Axovant Sciences nine months ago, you’re down 93 bucks.”

STAT further points out, “In biotech circles, the Axovant debacle became a referendum on Ramaswamy, who left a career as a hedge fund manager to build a constellation of biotech companies at work on drugs licensed from other firms.”

On the one hand, you have to admire someone who swings for the fences. But as any baseball fan knows, you’ve got to hit a homerun periodically if you do, and so far Ramswamy’s companies are striking out. That doesn’t mean all of them will—it seems likely that some of them, which are taking less risky approaches than Axovant, will get a break and become profitable. But gene therapy and Parkinson’s disease is still a tricky and difficult area to be taking big chances in. Maybe it’s good someone is willing to.

https://bit.ly/2xPwzLo

Zymeworks cut to neutral by Citi

Zymeworks downgraded to Neutral from Buy at Citi. Citi analyst Yigal Nochomovitz downgraded Zymeworks to Neutral while raising his price target for the shares to $20 from $18. The analyst believes the good ZW25 data at ASCO are now reflected in the valuation. Further, he sees a lack of near-term share catalysts

https://bit.ly/2xMd6LB