Thread by @BRAINCURES

With passage of the National Alzheimer’s Project Act (NAPA) in January 2011 and the subsequent “National Plan to Address Alzheimer’s Disease”, the war on Alzheimer’s has only just begun. But one key aspect is glaringly absent: specific funding commitments
science.org/doi/10.1126/sc…

More than 5 million Americans now suffer from Alzheimer, and that number is expected to more than double by 2050. Between 1998-2011, there were 101 unsuccessful AD drugs in development and only three approvals (none since 2003)
@AndrewWLo Kenneth @KosikLab
science.org/doi/10.1126/sc…

"If a single drug-development program takes 13 years
from beginning to end and has a 5% probability of success, the expected waiting time for the next approved Alzheimer's disease drug is 260 years"
-@AndrewWLo, Carole Ho, Jayna Cummings, @kennethskosik

https://twitter.com/westr/status/479626333723828224?s=20&t=nN-C4YvWJj-dD0adp2yJXw

A systematic effort to identify, prioritize, and categorize preclinical pathways that culminates with lead compounds for each hypothesis category could generate a portfolio with sufficient scientific support to justify multiple simultaneous clinical trials
science.org/doi/10.1126/sc…

With a 5% success rate among independent trials, 100 or more shots may be needed to yield an attractive
investment; this requires $50 billion and the identification of nearly twice as many potential
therapeutic targets than we currently have for Alzheimer
science.org/doi/10.1126/sc…

The ideal megafund business model will be a new hybrid of a drug-royalty investment company (for late-stage assets), a biotech venture-capital fund (for early-stage
clinical assets), and a multiproject platform such as the @ncats_nih_gov @AndrewWLo #scipol
science.org/doi/10.1126/sc…

Alzheimer's disease portfolio management must implement:
-state-of-the-art patient enrollment criteria
-expanded enrollment searches through community-based brain shops
-Internet-based screening
-a national institutional review board for AD clinical trials
science.org/doi/10.1126/sc…

@AndrewWLo et al believe that a collective effort among biopharma stakeholders—VC, pharma industry leaders, financial engineers, patient advocacy groups, and philanthropists—is both necessary and sufficient to successfully launch and manage an AD megafund
science.org/doi/10.1126/sc…

Probability of approval and the launch of a neurologically active drug at the start of a phase 1 study is 9%, 15% at the start of phase 2, with the probability increasing to 50% at the start of phase 3 based on neurology 2003-2011 product phase transitions
science.org/doi/10.1126/sc…

Parallel Discovery of Alzheimer's Therapeutics

"If a $600 million investment in year 0 produces a drug worth $12.3 billion in year 13, this represents a compound annual rate of return of ($12.3/$0.6)1/13 − 1 = 26.1% over the 13-year development period"
science.org/doi/10.1126/sc…

Forest Laboratories reported Namenda’s net sales for the year ending on 31 March 2013 to be greater than $1.5 billion. Estimated peak sales of potential anti-amyloid biologics such as solanezumab are expected to reach major market sales of $5.5 billion
science.org/doi/10.1126/sc…

Alzheimer's disease project with a high degree of validation
Aβ antibodies (6)
Pyro Aβ #antibodies (3)
Antibodies against soluble oligomers (3)

Medium validation
β-secretase inhibitors (6)

Low validation
γ-secretase #inhibitors and modulators (3)
#EndAlz

https://twitter.com/westr/status/479626333723828224?s=20&t=Lwi0hYsKCXvxihlJeAa7EQ

The fact that Alzheimer's disease therapeutics take so much longer to develop than do many other types of drugs implies that 20-year fixed patent terms are less valuable and pharma will be less motivated to invest @AndrewWLo @kennethskosik @ScienceMagazine
science.org/doi/10.1126/sc…

Unless more scientific progress is made so that the
probability of success is higher and more shots on goal become available, the private sector seems unlikely to produce effective Alzheimer's disease-AD therapies over the next few decades @kennethskosik
science.org/doi/10.1126/sc…

The government can greatly accelerate the development of Alzheimer's disease (AD) therapeutics in at least four ways:
i) by providing guarantees for the debt of an AD megafund;
ii) by starting the patent clock upon commercialization
rather than invention
science.org/doi/10.1126/sc…

The government can greatly accelerate the development of Alzheimer's disease (AD) therapeutics in at least 4 ways:
iii) by increasing the duration of patent protection from 20 to 30 years for AD therapeutics that meet a sufficiently high efficacy threshold
science.org/doi/10.1126/sc…

For the fiscal year (FY) ending 30 September 2012 (FY12), @NIH dedicated only $503 million for Alzheimer's research, and the @BarackObama administration invested only $50 million. NIH funding for cancer research in the same year was more than $5 billion

https://twitter.com/BRAINCURES/status/1585230324816293888?s=20&t=Lwi0hYsKCXvxihlJeAa7EQ

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