4 ms·

I don't know much about Stemcentrx - why do you think they will fail? Their science page sounds reasonable; antibody-drug conjugates don't seem far-fetched and

I don't know much about Stemcentrx - why do you think they will fail? Their science page sounds reasonable; antibody-drug conjugates don't seem far-fetched and I don't think they're the only ones pursuing that therapeutic paradigm.

w1ntermute 11y ago
Stemcentrx does seem the most reasonable of the three companies I mentioned from a scientific standpoint, but this area is fraught with prior failures[0]. It's just the nature of the industry. Also[1]: > The company says that they’re doing 150 xenografts a day (!) But their rationale is that trying to culture CSCs in vitro runs the risk of having them change character too much, making any assays using them unreliable. My guess is that they’re right about that, but my worry is that xenograft tumors themselves are already unreliable enough to cause trouble (and I have no idea of what happens to them after you “passage” them through multiple animals). Xenograft models are, of course, well known in oncology drug discovery, but one of the things that’s well known about them is that they’re the pure example of “necessary but nowhere near sufficient”. If your drug fails in a xenograft, it will probably fail in the clinic. But if your drug works in a xenograft, it will probably fail in the clinic, too. The odds get better, but they go from “extremely likely not to work” to “pretty likely not to work”, and you take what you can get in this business. > So how’s Stemcentrx doing in their cell hunt? They’re not going to tell Technology Review, naturally, but as the article mentions, the entire CSC hypothesis has been taking some hits recently. It’s still very much an open question. How many tumor types are driven by stem cells, whether they can be targeted (and how), how to tell when such an approach is indicated at all – there are a lot of open questions. It seems very likely that there are cell types inside a given tumor population that are more aggressive and likely to spread, but whether that narrows down to a particular stem cell group, I don’t know. What if there are 234 cell types in some particular tumor, and (say) fourteen of them are the ones to really worry about? What then? Will there be a common mechanism to target these, or not? 0: https://www.bostonglobe.com/business/2015/09/28/verastem-shares-plunge-after-company-halts-cancer-drug-trial/trHendPQ0ewSqLm2pixltJ/story.html https://www.bostonglobe.com/business/2015/09/28/verastem-sha... 1: http://blogs.sciencemag.org/pipeline/archives/2015/09/09/chasing-cancer-stem-cells http://blogs.sciencemag.org/pipeline/archives/2015/09/09/cha...
jamesad 11y ago
Stemcentrx must be doing something unique as they were recently named the best new drug developer at the recent antibody-drug conjugate (ADC) Summit in San Diego, and have been the topic of some flattering press about their lead compound (http://www.firstwordpharma.com/node/1319074?tsid=28#axzz3nF03Jv4Z http://www.firstwordpharma.com/node/1319074?tsid=28#axzz3nF0...). Other presentations showing clinical activity are also below: http://player.meta-fusion.com/late-breaking-abstract-safety-activity-and-response-durability-assessment-of-single-agent-rovalpituzumab-tesirine-a-delta-like-protein-3-dll3-targeted-antibody-drug-conjugate-adc-in-small-cell-lung-cancer-sclc http://player.meta-fusion.com/late-breaking-abstract-safety-... http://player.meta-fusion.com/late-breaking-abstract-a-phase-1-study-of-pf-06647020-an-antibody-drug-conjugate-targeting-ptk7-in-patients-with-advanced-solid-tumors http://player.meta-fusion.com/late-breaking-abstract-a-phase...
StewsNews 11y ago
Lumping Stemcentrx in with the others is extremely ill reasoned imo. The most basic of google searches show some pretty impressive stuff being done there. http://stm.sciencemag.org/content/7/302/302ra136 http://stm.sciencemag.org/content/7/302/302ra136 http://www.esmo.org/Conferences/Past-Conferences/European-Cancer-Congress-2015/News/First-Targeted-Treatment-for-Small-Cell-Lung-Cancer-Shows-Promise http://www.esmo.org/Conferences/Past-Conferences/European-Ca... While the second link is only phase 1, those are some impressive numbers. Finally, their clinical trials page (http://stemcentrx.com/clinical-trials.html http://stemcentrx.com/clinical-trials.html) shows two Pfizer collaborations, pretty sure Pfizer has a pretty good pulse on these things.
- w1ntermute 11y ago
  As I stated in the sibling comment, Stemcentrx is indeed much more reasonable than either Theranos or Nootrobox. However, a $5B valuation is still absurdly optimistic when you consider the comps. There have been massive setbacks at Verastem even after getting to phase 2[0], and Verastem's science originated from a top MIT research lab. 0: https://www.bostonglobe.com/business/2015/09/28/verastem-shares-plunge-after-company-halts-cancer-drug-trial/trHendPQ0ewSqLm2pixltJ/story.html https://www.bostonglobe.com/business/2015/09/28/verastem-sha...
  - StewsNews 11y ago
    Agreed, that is a lot if true, the MIT article[0] gave a 3 billion number and also mentions that the latest valuation was determined by Fidelity not some silicon valley VC firm. This all leads me to stick with the assertion that I would not lump the three in any way. 0: http://www.technologyreview.com/news/541006/peter-thiel-backs-biotech-unicorn-fighting-cancer-stem-cells/ http://www.technologyreview.com/news/541006/peter-thiel-back...
    - w1ntermute 11y ago
      The latest valuation is $5B, according to the WSJ[0]. The latest (series G) round was led by Fidelity, but Founders Fund, ARTIS Ventures, and SV Bank also participated in it[1]. Also, there's actually talk of Fidelity bringing sanity to startup valuations[2,3], rather than pumping them up even higher. You're right that Stemcentrx, unlike Theranos or Nootrobox, doesn't smell of SV hucksterism. However, rather than comparing Stemcentrx to Theranos or Nootrobox, compare them to OncoMed, Verastem, and Stemline, which have current public valuations of $700M, $65M, and $116M, respectively. And none of them ever exceeded $1.2B in their public valuations. 0: http://blogs.wsj.com/venturecapital/2015/09/16/peter-thiel-backed-stemcentrx-emerges-with-5-billion-valuation/ http://blogs.wsj.com/venturecapital/2015/09/16/peter-thiel-b... 1: https://www.crunchbase.com/funding-round/7db717567346f07e604cb2feb8472cb0 https://www.crunchbase.com/funding-round/7db717567346f07e604... 2: http://fortune.com/2015/11/11/snapchat-isnt-the-only-startup-in-fidelitys-crosshairs/ http://fortune.com/2015/11/11/snapchat-isnt-the-only-startup... 3: http://fortune.com/2015/11/12/fidelity-marks-down-tech-unicorns/ http://fortune.com/2015/11/12/fidelity-marks-down-tech-unico...

w1ntermute 11y ago

Stemcentrx does seem the most reasonable of the three companies I mentioned from a scientific standpoint, but this area is fraught with prior failures[0]. It's just the nature of the industry. Also[1]: > The company says that they’re doing 150 xenografts a day (!) But their rationale is that trying to culture CSCs in vitro runs the risk of having them change character too much, making any assays using them unreliable. My guess is that they’re right about that, but my worry is that xenograft tumors themselves are already unreliable enough to cause trouble (and I have no idea of what happens to them after you “passage” them through multiple animals). Xenograft models are, of course, well known in oncology drug discovery, but one of the things that’s well known about them is that they’re the pure example of “necessary but nowhere near sufficient”. If your drug fails in a xenograft, it will probably fail in the clinic. But if your drug works in a xenograft, it will probably fail in the clinic, too. The odds get better, but they go from “extremely likely not to work” to “pretty likely not to work”, and you take what you can get in this business. > So how’s Stemcentrx doing in their cell hunt? They’re not going to tell Technology Review, naturally, but as the article mentions, the entire CSC hypothesis has been taking some hits recently. It’s still very much an open question. How many tumor types are driven by stem cells, whether they can be targeted (and how), how to tell when such an approach is indicated at all – there are a lot of open questions. It seems very likely that there are cell types inside a given tumor population that are more aggressive and likely to spread, but whether that narrows down to a particular stem cell group, I don’t know. What if there are 234 cell types in some particular tumor, and (say) fourteen of them are the ones to really worry about? What then? Will there be a common mechanism to target these, or not? 0: https://www.bostonglobe.com/business/2015/09/28/verastem-shares-plunge-after-company-halts-cancer-drug-trial/trHendPQ0ewSqLm2pixltJ/story.html https://www.bostonglobe.com/business/2015/09/28/verastem-sha... 1: http://blogs.sciencemag.org/pipeline/archives/2015/09/09/chasing-cancer-stem-cells http://blogs.sciencemag.org/pipeline/archives/2015/09/09/cha...

jamesad 11y ago

Stemcentrx must be doing something unique as they were recently named the best new drug developer at the recent antibody-drug conjugate (ADC) Summit in San Diego, and have been the topic of some flattering press about their lead compound (http://www.firstwordpharma.com/node/1319074?tsid=28#axzz3nF03Jv4Z http://www.firstwordpharma.com/node/1319074?tsid=28#axzz3nF0...). Other presentations showing clinical activity are also below: http://player.meta-fusion.com/late-breaking-abstract-safety-activity-and-response-durability-assessment-of-single-agent-rovalpituzumab-tesirine-a-delta-like-protein-3-dll3-targeted-antibody-drug-conjugate-adc-in-small-cell-lung-cancer-sclc http://player.meta-fusion.com/late-breaking-abstract-safety-... http://player.meta-fusion.com/late-breaking-abstract-a-phase-1-study-of-pf-06647020-an-antibody-drug-conjugate-targeting-ptk7-in-patients-with-advanced-solid-tumors http://player.meta-fusion.com/late-breaking-abstract-a-phase...

StewsNews 11y ago

Lumping Stemcentrx in with the others is extremely ill reasoned imo. The most basic of google searches show some pretty impressive stuff being done there. http://stm.sciencemag.org/content/7/302/302ra136 http://stm.sciencemag.org/content/7/302/302ra136 http://www.esmo.org/Conferences/Past-Conferences/European-Cancer-Congress-2015/News/First-Targeted-Treatment-for-Small-Cell-Lung-Cancer-Shows-Promise http://www.esmo.org/Conferences/Past-Conferences/European-Ca... While the second link is only phase 1, those are some impressive numbers. Finally, their clinical trials page (http://stemcentrx.com/clinical-trials.html http://stemcentrx.com/clinical-trials.html) shows two Pfizer collaborations, pretty sure Pfizer has a pretty good pulse on these things.

w1ntermute 11y ago
As I stated in the sibling comment, Stemcentrx is indeed much more reasonable than either Theranos or Nootrobox. However, a $5B valuation is still absurdly optimistic when you consider the comps. There have been massive setbacks at Verastem even after getting to phase 2[0], and Verastem's science originated from a top MIT research lab. 0: https://www.bostonglobe.com/business/2015/09/28/verastem-shares-plunge-after-company-halts-cancer-drug-trial/trHendPQ0ewSqLm2pixltJ/story.html https://www.bostonglobe.com/business/2015/09/28/verastem-sha...
- StewsNews 11y ago
  Agreed, that is a lot if true, the MIT article[0] gave a 3 billion number and also mentions that the latest valuation was determined by Fidelity not some silicon valley VC firm. This all leads me to stick with the assertion that I would not lump the three in any way. 0: http://www.technologyreview.com/news/541006/peter-thiel-backs-biotech-unicorn-fighting-cancer-stem-cells/ http://www.technologyreview.com/news/541006/peter-thiel-back...
  - w1ntermute 11y ago
    The latest valuation is $5B, according to the WSJ[0]. The latest (series G) round was led by Fidelity, but Founders Fund, ARTIS Ventures, and SV Bank also participated in it[1]. Also, there's actually talk of Fidelity bringing sanity to startup valuations[2,3], rather than pumping them up even higher. You're right that Stemcentrx, unlike Theranos or Nootrobox, doesn't smell of SV hucksterism. However, rather than comparing Stemcentrx to Theranos or Nootrobox, compare them to OncoMed, Verastem, and Stemline, which have current public valuations of $700M, $65M, and $116M, respectively. And none of them ever exceeded $1.2B in their public valuations. 0: http://blogs.wsj.com/venturecapital/2015/09/16/peter-thiel-backed-stemcentrx-emerges-with-5-billion-valuation/ http://blogs.wsj.com/venturecapital/2015/09/16/peter-thiel-b... 1: https://www.crunchbase.com/funding-round/7db717567346f07e604cb2feb8472cb0 https://www.crunchbase.com/funding-round/7db717567346f07e604... 2: http://fortune.com/2015/11/11/snapchat-isnt-the-only-startup-in-fidelitys-crosshairs/ http://fortune.com/2015/11/11/snapchat-isnt-the-only-startup... 3: http://fortune.com/2015/11/12/fidelity-marks-down-tech-unicorns/ http://fortune.com/2015/11/12/fidelity-marks-down-tech-unico...