CIRM success story dies quiet death

A once-heralded research venture by the state of California that targeted “don’t eat me” signals that protect cancer cells has now ended. The potential treatment’s obituary boiled down to one phrase repeated six times and buried deep in a corporate document.

That amounts to $816 million per mention, based on what was paid for the company that grew out of the state-backed research.

The state agency involved is the California Institute for Regenerative Medicine (CIRM), created in 2004 via a ballot initiative. CIRM supported the development of the potential cancer treatment at Stanford University with $45 million, leading to the creation of a company called Forty Seven. Inc. In 2020, Gilead, Inc., purchased the company for $4.9 billion.

“To say this is incredible would be an understatement!” said then-CIRM president Maria Millan in a Capitol Weekly article at the time.

“It’s not every day that a company and a concept that you helped support from the very beginning gets snapped up for $4.9 billion,” the agency wrote in 2020 on its blog, The Stem Cellar.

“CIRM has supported this program from its very earliest stages, back in 2013, when it was a promising idea in need of funding.”

But late last week, Gilead dropped its bad news ever so quietly starting on page 34 of its first quarter financial reports. “Removed from the pipeline,” the Foster City, Ca., company repeated six times in the document about its “don’t eat me” projects.

A sharp-eyed reporter for Fierce Biotech, Nick Paul Taylor, spotted the terse language and put it together with the deal more than four years ago. “A $4.9 billion hole has appeared in Gilead’s pipeline. After years of setbacks, the big biotech dealt a final blow to its anti-CD47 monoclonal antibody magrolimab Thursday by removing the remaining solid tumor trials from its pipeline,” Taylor wrote on Fierce Biotech, a well-known industry online news site.

“The pipeline update marked a muted end to a molecule that was once central to Gilead’s cancer plans. Analysts saw the antibody as a potential (product) that could unlock opportunities across a wide range of blood cancers and solid tumors.”

Gilead’s abandonment of magrolimad was triggered by concerns from federal regulators and poor results. Earlier this year, the firm discontinued one magrolimab phase three clinical trial that “demonstrated futility and an increased risk of death… primarily driven by infections and respiratory failure,” a Feb. 7 company statement said.

The investigational therapy targeted a protein called CD47, which can provide a “do not eat me” signal that allows cancer cells to avoid destruction. The treatment aimed to neutralize the signal and allow the patient’s own immune system to eradicate the cancer cells.

The end of magrolimab is not good news for Gilead or CIRM, but not all other parties lost out. Stanford University received $67 million from the sale of Forty Seven. Irv Weissman, the Stanford researcher who developed the don’t-eat-me approach, snagged $191 million. CIRM received $15.6 million.

The agency’s intellectual property policy is aimed at encouraging the delivery of treatments to patients — not generating huge royalties.

While the fate of the $4.9 billion investment would seem to be a significant blow, Gilead did not announce what plans it has, if any, to squeeze out revenues or profit from the intellectual property or other assets purchased with Forty Seven.

The CD47 story highlights the financial risk involved in biomedical research and the risk that the $12 billion cost of the CIRM may not be recouped by its “angel investors,” the California taxpayers. The agency’s “business model” assumes that the payoff for all of its research will ultimately be the delivery of revolutionary treatments that will cure previously uncurable diseases.

But after nearly 20 years, 1,400 grants, an estimated 3000 published papers by awardees and 103 clinical trials, CIRM has yet to help finance a stem cell treatment that is available to the general public.

Neither CIRM or Weissman responded to queries on Friday concerning Gilead’s abandonment of magrolimab.

Jensen is a retired newsman and has covered CIRM for 19 years on his newsletter, the California Stem Cell Report. He authored the book, “California’s Great Stem Cell Experiment,” in 2020.