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Infinity’s Difficult History

Infinity Pharmaceuticals today announced that it’s shutting down R&D operations. This comes after disappointing clinical results for a PI3K inhibitor it’s been developing (duvelisib), news which has sent the company’s stock down (at this moment) nearly 70%. And that comes after the 2012 failure of another clinical candidate, saredigib. Which came after the 2009 failure of another clinical candidate, the HSP90 compound retaspimycin in a GIST trial, which failed in another clinical effort against non-small-cell lung cancer in 2013.

This is not how things were supposed to go. You can go back to this hopeful Forbes piece from 2005 for a look at how the future was. The article focuses on the HSP90 era of the company, and I have to say, HSP90 has not (to the best of my knowledge) worked out for anyone. By way of illustration the rival companies mentioned in that piece had different fates – Conforma Therapeutics was bought by Biogen in 2006, but its HSP90 inhibitor (which was renamed BIIB021) never seemed to amount to very much, although it did show some activity against GIST in the clinic. Kosan Biosciences was acquired by Bristol-Myers Squibb in 2008, but its lead HSP90 compound was dropped from development a couple of years later.

Infinity stayed unbought, but as that first paragaph shows, it’s been a rough ride. I can’t think of a better illustration of how hard drug development is, and how it is no respecter of good ideas, hard work, and talent. Let me rephrase that – all these are necessary to succeed in the biopharma business, but (sadly) they are nowhere near sufficient. Nothing’s sufficient. Not yet. Anyone who tells you different is trying to sell you something. Might be a company, some stock, consulting voodoo, what have you, but anyone who says that they’ve got this business figured out is fooling themselves and/or you.

12 comments on “Infinity’s Difficult History”

  1. Peter Kenny says:

    If only they’d used Property Forecast Index….

  2. Condolences says:

    As someone who has interacted several times with Julian Adams who is Infinity’s head of R&D, I am deeply saddened to hear this. Adams had the right combination of critical attitude and enthusiastic creativity that are necessary for good drug discovery. But nature always turns out to be wilier than any man’s dreams and determination.

  3. Hap says:

    Sounds like investing. “You wouldn’t have to look (very hard) for the guy who knew how to pick stocks (or drugs) – just look for the line of millionaires at the door.”

  4. Barry says:

    Hsp90 emerged only circuitously as a potential cancer target. A phenotypic assay (cell proliferation in vitro) found geldanamycin. Fishing through cell lysates for what was retained on a column of immobilized geldanamycin found Hsp90. It’s now known that Hsp90 has over 100 client proteins, so the effects of inhibition would be hard to foresee; it is far, far from the sort of onco-fetal target protein that has no legitimate role in the adult.
    the argument for PI3-k as a cancer target is more orthodox; mutants correlate with a fair number of human cancers.
    It’s a tough field in which clinical failures are to be expected

  5. Design Monkey says:


    Another one bites the dust. Show must go on.

    Also: Navigare necesse est. Sort of.

  6. pete says:

    Sorry to see this, too. From my perspective, Infinity appeared as one of the quality bright spots in the young(ish)-biotech firmament. Sheesh…

  7. KarmaChem says:

    The Infinity PI3K-delta drug was a direct rip-off of idelalisib/Zydelig from ICOS >>>Calistoga>>Gilead. Just sayin. Switched one N for C in the aryl ring and had slightly different halo and alkyl groups–BTW same groups that were featured in top compounds in idelalisib patent. Expecting this to show some exceptional behavior turns out to have been wishful thinking. In my opinion they are lucky to have gone this far and gotten so much time and money for a really trivial me-too compound. Feel bad for the staff though. Most of us have all been through it.

  8. CMCguy says:

    I think you are correct Derek that this is a particularly illustrative example of a drug development being a difficult and unpredictable game. This PII study actually did met the target end points as a monotherapy but since did not obtain responses to match or exceed other similar drug makes it hard to rationalize continued expenditures for PIII and highlights again the direct risks for the R&D people who are typically the first wave to be impacted when enter costs constraint mode. It appears there are other trials combining other treatments where even if they demonstrate more positive results it will be difficult to garner support to advance.

  9. steve says:

    Agree with Condolences; Julian Adams’ work on bortezomib was extremely insightful. Before I heard him talk I never would have thought that blocking something as fundamental as the proteosome would result in a useful therapeutic. It turns out it’s all about dose and regimen; cancer cells can’t recover as quickly from the insult. It’s a shame this venture didn’t result in equally useful drugs but I’m sure it’s not from lack of scientific talent.

  10. LL says:

    And in the meantime Médecins du Monde starts a vendetta against pharma industries and the price of drugs… Pretty discouraging.

  11. pwm says:

    Have to agree with KarmaChem that due to the extreme structural similarity, it is hard to imagine a differentiating therapeutic and/or safety profile for duvelisib vs idelalisib. Hope upon hope may be duvelisib may possess a more efficacious therapeutic profile due to its dual inhibition of delta and gamma (although supposedly not at the 25 mg dose tested in the trial), but certainly not a more favorable safety profile (which seems to be critical for combination therapy for this class of compounds).

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