Thread by @jeff_sharman

BTK inhibitors have transformed the lives of many patients with Chronic Lymphocytic Leukemia and other lymphomas. These drugs "exploded" onto the scene in 2013-2014 and have fundamentally changed the way we treat the disease. What many people don't know is how it all happened..

In 2004 I became convinced that turning off B-cell receptor signaling would cause cancerous b-cells to stop growing. This theory came into focus based upon an understanding of epstein barr virus protein LMP2A, EBV relationship to Hodgkin lymphoma, and other breadcrumbs

I decided the best way to turn off the receptor would be to use drugs which shut off the signaling pathways emanating from the B cell receptor - notably SYK.

Fortunately Ron Levy M.D. of Stanford was willing to let me test the hypothesis in the laboratory

I acquired #fostamatinib from #RigelTherapeutics and set to work - quickly learning that I didn't belong in the lab at all (not my skill set)

Fortunately, others came to the similar idea and shortly thereafter we began testing the compound in patients with lymphoma

Our results were presented in the plenary session at ASH in 2010 by Dr. Friedberg
pubmed.ncbi.nlm.nih.gov/19965662/

At the time #pharmacyclics was a zombie company almost left for dead but Richard Miller MD was at the helm and saw my patients with me at Stanford receiving fostamatinib.

I explained to him the hypothesis of BCR signaling inhibition which turned into a critical moment

He had PCI-32765, a molecule that inhibited the next enzyme in the BCR signaling pathway - BTK.

Based upon our experience with fostamatinib, we set up a consulting agreement and I helped design a study to test ibrutinib in patients with NHL/CLL

Graduating from Stanford, I had to find a job and I settled on a community practice job in Oregon at the Willamette Valley Cancer institute and turned the research project over to Daniel Pollyea - in the class behind me.

It took a year for the first cohort to enroll which is a disaster for a small biotech so Pharmacyclics reached out to my new group to see if we could assist enrolling patients into the study.

Shortly thereafter I treated the first CLL patients in the world with ibrutinib

What happened next was beyond anything I could ever imagine and has been turned into a novel that was published this week.

amazon.com/Blood-Money-Bi…

It is a dynamic story told by @nathanvardi which details the clash of powerful personalities resulting in enormous fortunes for investors along the way

Like many in the book - I never made a penny off of the original idea, but I am very proud that an idea I brought forward has resulted in so much good for so many patients

I love being a doctor and I would never trade that experience for the fortune I may have made had I followed the idea into industry... a choice that would have fundamentally re-routed the course of my life

I am also very grateful for the incredible hard work put forward by so many others without which the drug would have never made it so far.

Thank you @nathanvardi for telling the story! #ibrutinib #acalabrutinib #zanubrutinib #pirtobrutinib #cll #lymphoma #btk

@abbvie @CllSociety @DrNeilLove @AstraZeneca @LoxoLillyOnc @PatientPower @RigelPharma @BeiGeneGlobal