Investors pour $76 million into B round for Cortexyme’s “new” approach to Alzheimer’s. No, it doesn’t target Amyloid beta (Aβ); it’s bacterial and getting support from Pfizer, Paul Allen.

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The News:

With the evidence increasingly weighing in against amyloid beta as the best solo target for Alzheimer’s, startup Cortexyme Inc. (South San Francisco) has identified a brand-new target and now has a $76 million B round to put it through its first proof-of-concept study.

The scientific inspiration for the biotech comes from psychiatrist and former UC San Francisco associate professor Steve Dominy, who identified a bacterial pathogen that he believes plays a key role in the pathology of the disease, Endpoints reports. Initially working out of Johnson & Johnson’s JLABS Bay Area facility, Cortexyme has now completed animal studies as well as a Phase 1 safety test to set the stage for a Phase 2 human study.

Alzheimer’s remains the hardest target in drug R&D, taking down a series of contenders in a long lineup of failed studies over 10-plus years. Those failures, in turn, have inspired a hunt for better targets, combination approaches and a drive to treat patients at ever-earlier stages of the disease.

Cortexyme faces tough odds, but with the potential rewards for any approved therapy tipping the scales to the mega-blockbuster range, this remains the industry’s lottery ticket–with ultra-high risks and rewards to consider.

Cortexyme got started with some marquee backers, including Pfizer Inc. (which recently exited neurosciences), Takeda Ventures, Lamond Family, Breakout Ventures, and Dolby Family Venture, Sequoia Capital, Vulcan Capital, Verily Life Sciences, EPIQ Capital Group, RSL Investments and Huizenga Capital. An unidentified long-term mutual fund also joined the syndicate.

“Our streamlined, efficient approach to drug development allowed us to move from seed funding to Phase 1 data in less than four years,” said CEO Casey Lynch. “We’re committed to continuing to move swiftly through Phase 2 proof of efficacy studies in service of bringing new therapies to patients suffering from Alzheimer’s and related conditions.”

Steve’s Take:

As we age, our bodies are living longer and longer, but our brains still have the same short half-life. As we continue on this path, what we are seeing is that the rate of Alzheimer’s is going up and up as people live longer, in direct correlation.

That brings us to Australian physician and researcher Barry Marshall. In 1982, he and his collaborator Robert Warren discovered that the bacteria H. pylori could be cultured from and was a likely cause of ulcers.

This was met by a tidal wave of skepticism from the establishment at the time because everyone knew that ulcers were caused by spicy foods and stress. So, Marshall in 1984 decided to drink a petri dish of the bacteria to prove his case. He then experienced major GI symptoms, and fast-forwarding to 2005, the two researchers were awarded the Nobel Prize for their discovery. Ulcers are now routinely treated with antibiotics.

That brings us once again to bacteria, the microbiome Alzheimer’s and Cortexyme. To me it resembles a “new” approach by a nimble, seemingly well-reasoned and now well-funded startup to solving the decades-old challenge to successfully combat AD. Not that the big houses haven’t thrown their money and top scientific brains at this graveyard of attempted efforts.

Pfizer, for one, recently started backing out of its neuroscience projects, including in Alzheimer’s and Parkinson’s disease, FierceBiotech reminds us. The big pharma dropped preclinical, early and midstage research programs, and cut around 300 jobs earlier this year.

At the time, Pfizer said it would set up a CNS-focused venture capital fund for external projects and may even license out the compounds in its portfolio for development. The company also canceled development of a compound for Huntington’s disease the year before.

And last month, Johnson & Johnson’s Janssen unit ended clinical trials for its BACE inhibitor atabacestat, following liver safety issues in late-onset Alzheimer’s patients.

However, Janssen said it “continues to maintain a strong commitment to discovering and developing new treatments for this devastating disease.”

Meanwhile, Roivant Sciences’ spinout, Axovant, recently came out with negative results in a Phase 2b trial of intepirdine in Lewy body dementia. Following a string of clinical failures, Axovant CEO David Hung, MD, resigned in February. The company had acquired intepirdine, a 5-HT6 inhibitor, from GlaxoSmithKline for just $5 million upfront in 2014.

By contrast, Cortexyme’s COR388 targets a pathogen discovered in the brains of Alzheimer’s patients by the startup’s co-founder and chief scientific officer, Stephen Dominy, MD, and employs a different mechanism of action compared to broad-spectrum antibiotics.

“Alzheimer’s has been a major medical and societal challenge for decades, and new approaches are clearly needed,” said Michael Dixon, a partner at Sequoia Capital, in a release. “Cortexyme is approaching an old problem in a whole new way–moving upstream to target an underlying driver of disease.”

In the company’s Phase 1 safety study launched in January, COR388 was well-tolerated by healthy volunteers aged 20 to 70, in single-ascending and multiple-ascending doses compared to placebo. The company said it also noted favorable pharmacokinetics and tissue distribution when given orally.

“We’re committed to continuing to move swiftly through Phase 2 proof of efficacy studies in service of bringing new therapies to patients suffering from Alzheimer’s and related conditions,” CEO Casey Lynch said.

This small South San Francisco upstart already boasts an A-list of investors, including the private equity unit of Microsoft cofounder Paul Allen and the family office of the founders of Waste Management.

“People think of Alzheimer’s being a graveyard, but really it’s a graveyard of beta amyloid,” said CEO Lynch. “It’s not that this indication is impossible to treat.”

In addition to amyloid, companies have looked at fragments of another protein, called tau, with limited success so far in Alzheimer’s, and that has resulted in a cottage industry of scientists and investors looking more closely at causes, rather than effects of the disease, and new approaches.

South San Francisco’s Denali Therapeutics Inc., for example, is developing ways that they hope will safely and effectively ferry antibodies and enzymes across a membrane known as the blood-brain barrier to attack neurodegenerative diseases such as Alzheimer’s.

Bottom Line:

A September 2017 report by GlobalData found that the Alzheimer’s disease market, worth $2.9 billion in 2016, is set to jump in value to $14.8 billion in 2026. The report attributed the forecasted rapid growth to the introduction of 20 new drug candidates, some of which have shown potential to prevent or slow the disease’s progression.

Steve's Take: I give #Cortexyme a thumbs-up for its science and bravery to fight #Alzheimer's! Click To Tweet

Upstart startup Cortexyme has the look and feel of a winner, although it’s miles and miles from proving its theory of a bacterial link to AD and the efficacy of its COR388 candidate. It will eventually have to offer its investors some proof of efficacy, otherwise off to the AD graveyard we go again.

I give it a thumbs-up for its science and bravery. And Casey Lynch is no Stanford dropout and huckster like Elizabeth Holmes of Theranos disrepute.

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