Synta’s fiASCO– Disappointing results but signal is still there

Last weekend, Synta (SNTA) reported updated results from a randomized phase II evaluating ganetespib in NSCLC (non-small cell lung cancer). Although the data set demonstrated a survival signal that merits advancing ganetespib to phase III, results were worse than last year’s interim analysis (discussed here). This triggered a sell-off in the stock, which was down 39% this week.

Putting disappointment aside, the clinical profile that emerges from the updated results is positive and should be regarded as reliable given the large size of the trial (252 patients). If these results are reproduced in the ongoing phase III, ganetespib will likely become a commonly used drug in 2nd/3rd line NSCLC patients with a clinical profile that resembles that of Avastin (Approved for 1st line NSCLC).   

Following the recent sell-off, Synta is undervalued even when applying a more conservative probability-adjusted valuation method that factors in the recent data. In addition, the market appears to ignore additional potential indications where ganetespib will likely have a role, especially ALK/ROS/RET mutations in lung cancer.

Updated data at ASCO

The trial accrued 252 patients who received Taxotere or Taxotere + ganetespib. Ganetespib led to a 2.4 month improvement in median overall survival (9.8 vs. 7.4 months) but the difference was not statistically significant (it trended towards significance, p=0.082). Importantly, there was a statistically significant improvement in progression-free survival (PFS) from 3.2 to 4.5 months (p=0.038).

A 2-month survival benefit is considered approvable in NSCLC (Avastin and Tarceva have a 2-month benefit in their labels), providing it is statistically significant. Synta’s phase III trial will enroll 500 patients, so it should be able to demonstrate a statistically significant benefit if ganetespib’s effect is real.

Activity was more pronounced in patients who did not rapidly progress on 1st line treatment (non-rapid progressors, accounted for 70% of participants). In this subgroup, ganetespib led to a statistically significant 4-month survival benefit, which prompted Synta to focus on this subgroup in the phase III. While this decision has the potential to improve the outcome, it is based on a retrospective subset analysis that should be treated cautiously.

Comparison to ESMO 2012 update          

As a standalone observation, the survival signal in the “intend-to-treat” (ITT) population is positive, but it is worse than that reported at the previous update at ESMO 2012 (see table below). Although the estimated medians remained similar (2-3 month difference), the hazard ratio (HR), which captures the entire difference between the survival curves (not just at the medians) deteriorated.

ganetespib dataAt the prior analysis, HR was 0.688 for the entire population and 0.568 for patients with a follow up of >6 months. The recent analysis showed a HR of 0.82. Since it was conducted when all patients had a follow up of >6 months, this represents a substantial increase (The lower a hazard ratio is the better), leading some to suggest that the survival benefit is diminishing as the trial progresses and is not likely to be replicated in the phase III trial. (See Adam Feuerstein’s write up)

There was also skepticism around the signal in non-rapid progressors because survival in patients who received Taxotere was 1 month shorter than the ITT Taxotere arm. Since these patients have more indolent disease, they are expected to have better survival, not worse.

Ganetespib could still have an “Avastin-like” profile

The most important and reliable piece of data remains the ITT survival analysis, as it represents an objective prospectively defined endpoint from a fairly large sample size. In order to put ganetespib’s results in context, it should be analyzed in light of the only targeted therapy approved in combination with chemotherapy for NSCLC. Similarly to ganetespib,  Avastin was evaluated in predominantly adeno patient population and was given as maintenance.

It is important to stress that I am not trying to directly compare the 2 drugs as they have been evaluated in different settings (e.g. treatment line, backbone chemotherapy). Instead, the comparison gives a sense for how an active targeted therapy behaves when added to chemo in NSCLC.

As can be seen in the table below, both agents generated a similar survival benefit and hazard ratio. The median PFS benefits appear numerically comparable (both statistically significant) but Avastin has a better hazard ratio as well as response rate difference.  Obviously, Avastin’s data is from a large phase III trial, which was powered to show a statistically significant survival benefit. Ganetespib’s data is from a smaller phase II trial that has to be validated in phase III. Synta’s decision to limit recruitment to non-rapid progressors may limit ganetespib’s market potential but may also lead to a more profound effect.

ganetespib vs. AvastinSummary

Ganetespib did not meet investors’ expectations but the phase II trial generated a clear survival signal that trended towards statistical significance. As the trial was larger than similar trials in NSCLC (e.g. Metmab, tivantinib), the survival signal appears reliable. The activity in non-rapid progressors is impressive but should be taken with a grain of salt.

In order to reach a price target, I decided to use a more conservative probability-adjusted valuation which assumes only a 20% likelihood of success. These 20% include a scenario in which ganetespib has an “Avastin-like” profile (2-month survival benefit, HR 0.8) or an improved profile based on the non-rapid progressors cohort from the phase II (4-month benefit, HR 0.6). As can be seen in the table below, even when such a low likelihood of success is assumed, Synta’s market cap should be ~$600M solely based on this indication.

ganetespib valuationThis excludes ganetespib’s potential in a group of rare mutations in lung cancer (ALK, ROS1 and RET translocations), representing ~7% of NSCLC cases. Activity for Hsp90 inhibitors in ALK+ patients has been demonstrated with 3 different inhibitors (Synta’s ganetespib, Infinity’s IPI-504 and Novartis’ AUY922) so it appears that this is a reliable class effect. There is still no published clinical experience in RET+ and ROS1+ patients but there is strong scientific rationale for why these fusions are dependent on HSP90. Earlier this year, Synta published preclinical results which demonstrate impressive activity of ganetespib in both mutations.

Lastly, Infinity (INFI) is expected to announce results from a phase II trial evaluating its Hsp90 inhibitor, IPI-504, in combination with Taxotere for NSCLC. Although there are trial design differences and IPI-504 is considered less potent and more toxic than ganetespib, it will be interesting to see if Infinity sees a survival signal (especially in adeno patients).

 Portfolio holdings – June 8th 2013

biotech portfolio - June 8th 2013 biotech etfs

85 thoughts on “Synta’s fiASCO– Disappointing results but signal is still there

  1. Ohad
    I am really confused with the results.
    (1) Rapid progression should correspond to over-expression of Hsp90, shouldn’t it? This should be their targeted population, but they excluded them.
    (2) The other big concern is that the OS of ‘non-rapid progressors” was 1 month shorter. If they were living longer by say 1 month, as you would expect, that would change dramatically the picture.
    I am afraid that they fooled themselves with the preliminary Galaxy 1 results. If you combine 1 and 2 it would point out to a wrong Phase III design.
    Any thoughts?
    –andre–

  2. 1- Don’t know about correlation between Hsp90 and rapid progressors. None of the Hsp90 programs I am familiar with stratify patients based on Hsp90 expression, not sure that this is relevant as opposed to certain mutations in client oncogenes.

    2- Agree about that point, which I mentioned above as a reason to be skeptic about this subset. If you look at the confidence intervals for non-rapid progresors in both arms they overlap so the difference there doesn’t appear dramatic other than the median. the good HR for this subset is still intriguing.

    The major finding was the OS trend in the entire population, without using any subsets or retrospective analyses. Excluding rapid progressors could turn out to be irrelevant but I don’t see any downside to it other than limiting the drug’s market potential.

    Ohad

  3. Ohad
    Let’s hope it is irrelevant.
    Do you have the HR for the entire population before the 6 mo follow up – just to compare to 0.688 from prior analysis? It should be > 0.82. If we apply the same ratio as from ASCO 2012 the HR would be 0.992, which would mean no benefit at all.

    Another topic, do you follow EPZM? They had an impressive IPO and even more impressive line of partners – Celgene, Eisai, Glaxo SK, Roche, Abbott. I know it is too early to make any meaningful financial evaluation, but I am wondering if you have any thoughts about the scientific merits of their HMT inhibitor program(s). They said that they identified 96 HMT targets, which is another impressive number.
    Do you know any other company working in this area, which could validate their approach?
    Thanks
    — andre–

  4. All patients in the ASCO analysis have 6 months of follow up, so there are no patients who have less than 6 months.

    EPZM had a great IPO, which is even more impressive given the fact most of their stuff is preclinical. HMTs are considered a very promising family of targets but as you said it remains to be seen how they will pan out in the clinic. To my knowledge, they have the most advanced program in development.

    Ohad

  5. Yes, this is despite the unclear results in CRC. They will present p3 lung data with a particular fovus cMET+ tumors that could have positive readthrough to the liver cancer p3.
    I also like their p1 programs (Akt, FGFR), both targets are gaining a lot of momentum. Although ArQule isn’t in the lead here, these assets could be attractive for partners (like what happened with MEK or PI3K inhibitors several years ago).

    Ohad

  6. Hi ohad, at current lows which one in your opinion has the best buy value snta, arql, infi? thanks

  7. CURE MAGAZINE and the latest from ASCO including reports and video on the latest high interest PD-I treatment. PD-1 Inhibitors Are a Game Changer
    Michael Wong, melanoma oncologist and CURE advisory board member, explains how recent studies are targeting the PD-1 pathway and describes why there is so much excitement surrounding this new class of immunotherapy.
    media.curetoday.com

  8. I’d say so far, so good. They still haven’t hit MTD on 520 and the poster says that in Part B of the Phase 1b they expect to also dose escalate the Kyprolis portion of the combo. So, should have even better efficacy going forward provided safety cooperates.

  9. Ohad,

    I don’t see how ARRY’s 520 will ever be able to compete with elotuzumab in the crowded MM space as a combo treatment. Mr. Market certainly wasn’t impressed with the 520 data and neither was I. I hope we have more impressive results in MDS with 614, which we will probably know about at ASH.

    What do you know about ARRY’s collaboration with Genentech?

    Any more recent thoughts on EXEL?

  10. Richard, please share with us exactly how 520+Kyprolis combo won’t be able to compete with elotuzumab combo in MM. T.i.a. I think the data looks good so far, with caveat of it still being early, but there is chance for further efficacy as dosing is increased. I’d say it’s way too early to make a declaration such as yours.

  11. McBio,

    You’re talking about a very good drug with a good safety profile backed by BMY and ABBV that is in Phase III trials already. I don’t see 520 being competitive in this space, unless maybe the AAG marker gives it some advantage in those patients. And raising the dose to an MTD is liable to create tolerability and safety concerns. If ARRY can out-license 520, then fine. But I’d rather see them concentrate on 614 in a less crowded space like MDS. I believe MDS is a bigger market with probably a greater unmet medical need. Just my humble opinion.

  12. I think you’re trying to compare Phase 2 data for one drug to ongoing Phase 1 data for another drug. It’s hard enough comparing data across trials (e.g. don’t know if patient populations are apples-to-apple) but even more so when you’re comparing Phase 2 data of one drug to that of another that’s just in Phase 1 and hasn’t hit MTD and hasn’t had a chance yet to show full efficacy. I’m not saying ARRY-520 will end up better than, or even in the same ballpark as, elotuzumab but let’s at least wait until we can make a much better apples-to-apples comparison of the data. If 520 data ends up successful, I imagine ARRY will have a shot at their own big-name partner for the drug.

  13. ARRY-520, unlike elotuzumab, has clear activity as monotherapy. To date the promising results with elotuzumab were from a phase II comparing 2 doses of the drug with Revlimid but not to Revlimid alone. This makes me a little bit skeptic although the numbers in the trial were compelling.

    Ohad

  14. Thanks Ohad. The other odd thing about the elotuzumab combo data was the better response at the lower elotuzumab dose than high dose given 92% ORR with 10 mg/kg vs. 76% ORR with 20 mg/kg. Also, median PFS was 18.6 months in the high dose group but had not been reached in the low dose group. Seems kind of counterintuitive but could imply healthier patients in the low dose group.

  15. In general, EXEL is becoming a more diversified story which makes me feel more comfortable. Instead of being just a prostate cancer p3 company, they now have initial sales in MTC, p3 in RCC and liver cancer, potential accelerated approval for Ret mutated lung cancer, several p2 trials with the NCI and they also have their MEK inhibitor in p3 by Roche.

    This means they are gong to turn a lot of cards next year and hopefully one or more of these cards will be positive.

    Ohad

  16. The study wasn’t large, difference in ORR between two arms was from only 5 patients. It could be explained by much higher discontinuation rate from 20mg/kg arm due to AEs. 10mg/kg is the chosen dose for ph3.

  17. Listened to ARRY cc at WFC. They intend to submit for breakthrough designation for 520. Funny that Dr Pazdur was asking questions at the CC and he asked why they should consider 520 for accelerated approval Good answer from the CMO and Pazdur seemed pleased with it. Definitely a CC worth listening to.

  18. Was that really Pazdur? I thought the speaker was just acting as if he was Pazdur and having the ARRY CMO defend 520. Could be wrong. CMO defended 520 by noting the need for new novel MoAs. Also thought it interesting that ARRY presented with Takeda/Millennium, who could ultimately be a partner given combo trials of 520+Velcade. Takeda speaker did seem to push their all-oral regimens but seemed to leave door open at end for combining with other IV regimens (520?).

  19. It wasn’t Pazdur. It was the host pretending to be Pazdur and asking Dr. Needle to convince him that 520 should get “breakthrough therapy” designation.

  20. FWIW I don’t think 520 is eligible for breakthrough designation based on available data. If AAG holds as a biomarker, that could make it more realistic.

    Ohad

  21. Hi Ohad,

    is ONXX still a buy for you at current levels?

    who in this forum thinks we are close to a biotech bubble? there are a lot of IPOs, oversigned, prices rocketing up,…. I think it started similarly in 2000 (but was before my time on the stock market), didn’t it?

    greetings
    Christian

  22. Yes I still like ONXX, they are pretty diversified with 3 growth drivers – Kyprolis, palbo, and Stivarga. I hope they will make another acquisition soon.

    Yep, the biotech market is booming, especially the large cap biotechs (BIIB, AMGN, GILD), MID CAPS (VRTX, REGN, PCYC) and pharmas with good biotech exposure (Roche, BMY). The stream of IPO is very strong, which is great for investors looking for new opportunities.

    Don’t know if it’s a bubble or not, many claim that the price appreciation is supported by strong fundamentals (HCV, PD-1, oral drugs for CLL/NHL) and what we see is a correction towards less depressed PE multiples. (for examples, Mark Schoenebaum from ISI and Credit Suisse’s report titled “This is not a biotech bubble”)

    btw, these type of bubbles tend to stay longer than expected.

    Ohad

  23. My bad. I listened to the CC at work with a lot of interruptions :-) I thought it was strange that the FDA was at a Wells conference.

  24. On topic of biotech bubble, I think some names look frothy (I have no interest at all in these recent IPOs). But, I think you have to look at names individually and not just lump the entire sector together. I, by definition, tend to buy beaten down, out-of-favor companies so I certainly don’t think any of my holdings look expensive and I’m content to continue to hold, regardless if there are many other names like the recent IPOs that I think are by and large over-extended.

  25. I think it provides investors in small cap biotechs more opportunities to invest. Some of the companies are quite interesting with real meat on the bone. In many cases, valuation is very reasonable.

    Ohad

  26. Ohad,

    Have you ever looked that French biotech, Innate Pharmaceuticals? Partnered with BMY. Impressive management team.

    What IPO’s do you like? EPZM?

  27. I am familiar with them to some extent. The targets look very interesting biology-wise but the clinical data as monotherapy wasn’t impressive imo. The fact BMY thought it was a good target is a huge vote of confidence.

    I am still trying to digest the recent IPOs so I don’t have a concrete opinion on many of them. Still, most of them are backed by real and innovative programs. EPZM is too expensive for me, waiting for Agios’ IPO, beautiful science there although not in the clinic yet.

    Ohad

  28. Ohad
    Do you follow or have an opinion about NewLink Genetics?
    They have two platforms – HyperAcute immunotherapy and IDO pathway inhibitor. For IDO they claim that it is similar to PD-1 !?!

    About future IPOs – BIND seems to have an interesting technology. A targeted delivery, well differentiated from ADC of SGEN or TAP of IMGN.
    Two Phase II trials plus great partners – Amgen, Pfizer and AZN.
    Any opinion about their technology?
    –andre–

  29. I have serious doubts re NLNK’s p3 in resectable pancreatic cancer as it is based on a single arm p2 where patients received the vaccine and Gemzar. For combination regimens in particular, comparison to historical control is unreliable.

    IDO is an interesting target (INCY also has one) but comparing IDO inhibitors to PD-1 antibodies is a stretch. PD-1 antibodies have phenomenal activity as monotherapy. IDO inhibitors don’t (for now).

    BIND is very impressive in terms of technology and partnerships. Not sure their p1 results are that exciting (most patients were Taxotere naive). Still, they appear to reach a level of reobustness and reproducibility for their nanoparticles to draw so much interest from pharmas. Will be happy to buy some shares if they IPO.

    Ohad

  30. Thanks,
    I am also waiting for BIND and Agios’ IPOs.
    About NewLink – i also have some reserves about HyperAcute trials. However IDO pathway inhibitors are orally administered small molecules. They can be used in combination with other cancer therapeutics – good platform for partnering. Waiting to see if some big company will collaborate with them.
    –andre–

  31. Ohad
    There is an article today in Forbes about “The FDA’s Cancer Czar ….” Pazdur. It discussed a bit what breakthrough designation mean (actually not that much – just improved communication with FDA).
    Here is the list of the companies with such designations:
    One designation: ABBV, ALXN, BMY, Genmab+JJ, MRK, NVS, PFE+ONXX, Roche, Scioderm (private), GEVA.
    Two designations: VRTX
    Three designations: PCYC
    Pazduz call “ibrutinib data impressive”
    I am curious why you don’t have PCYC in your portfolio. Looks a clear winner to me
    –andre–

  32. Probably has something to do with the fact that PCYC already has a ~$6B market cap. What is the upside from that level? What if something goes wrong and either all the rosy projections don’t pan out or something else comes along that is at least comparable? All told, just because a drug is “great” doesn’t make the stock a great investment. And maybe the stock still will be; just playing devil’s advocate (but it’s why I have no interest myself).

  33. PCYC is indeed a clear winner who is anout to revolutionize treatment of several blood cancers. I even owned it at some point but sold too soon…
    As mcbio wrote, the main issue is valuation: it’s not a bubble given the fact ibrutinib will be a 3-4B drug but it’s not cheap either. If a market correction occurs, it could become attractive.

    Ohad

  34. Hi Ohad,
    Genmab today with a little crash. I see no fundamental reason for the dive. Is this an opportunity for you to buy more? Thanks.

  35. From what I understand, there was a research note/article which claimed Arzerra will not be able to compete despite the positive results. It was published in the journal by the name of AKTIE UGEBREVET. Their proce target is DKK 145.

    While I agree with their conclusion about Arzerra, daratumumab has the potential to more than compensate. Price is attractive imo.

    Ohad

  36. additional MEK162 study

    NOvartis seems really to be active with the ARRY drug

    http: // clinicaltrials.gov/ct2/show/NCT01885195?term=novartis&rcv_d=14

  37. Hard to say. They don’t need to raise money but something positive needs to happen to reverse the negative trend. They will have several data readouts at ASH (December) and p2 trials in inflammation that could provide that.
    I still believe their drug will eventually reach the market and will be able to bring at least several hundreds of millions in sales.

    Ohad

  38. Hi Ohad,

    do you know Astex Pharmaceuticals? What do you think of their pipline?

    Thanks,
    Martin

  39. Yeah, they are shaping up as a well diversified oncology play, have all the right targets (CDK4/6, Akt, FGFR) in their partnered pipeline, and 2 proprietary program in p2. Will try to accumulate in the coming months in stock goes down.

    Ohad

  40. Hey Ohad
    have you looked at the recent Imetelstat update in ET…. 100% hematological responses… the stock has been rebounding from its lows…
    What is your take. I thought you said you thought their valuation was too high a few month back wehn the share price was around $1.70…. what about now, considering the results, and the fact that this drug may work against many different times of hematological conditions?
    Thanks

  41. The drug clearly has clinical proof of concept but the indication is not viewed as attractive (Incyte and Novartis are not pursuing it). The value is in the investigator sponsored myelofibrosis trial, first results from which are expected at ASH. I would also carefully look at the safety profile which from I recall wasn’t benign.

    Ohad

  42. Thanks for the reply, very appreciated.
    also similar to Krypolis, it will be administred by IV, which might be a negative.

  43. hi Ohad,

    MOR will cover 1/3 of the global development costs.

    I know it is very hard to guess, because we do not know which combinations will be used etc, but what would be a wild guess for the total development costs from here?

    thanks
    Christian

  44. Congrats on another great pick Ohad. Appears to be true: AMGN => ONXX @ $120/shr. Thank you for all your great write ups and please continue the outstanding work you do for free :-)

  45. Thanks, Manish. Remember there’s nothing official as of yet.
    If AMGN pulls it off, they are getting an excellent deal. Not sure this is the case for ONXX…

    Ohad

  46. Ohad
    Thanks for the great call (ONXX – a must own bio in 2013).
    Now the offer is confirmed and as expected – rejected.

    I am a bit disappointed that the BOD put ONXX officially for sale (“…Onyx Board has authorized its financial advisor to contact potential acquirers who may have an interest in the Company…”)
    I expected that if they stay independent they could become eventually a major player.
    Why do you think the CEO and the BOD want to sell the company?
    Thanks —ande–

  47. In light of the offer, the directors are more or less duty bound to go out and ask for and look at other offers. But that does NOT mean they must recommend selling the company. They can then recommend an offer or recommend staying independent. These are generally referred to as “Revlon” duties, because the legal principles came up in a case involving Revlon. See links below for more specifics.

    https://www.boardmember.com/Article_Details.aspx?id=7348

    http://www.professorbainbridge.com/professorbainbridgecom/2012/08/revised-version-of-the-geography-of-revlon-land-posted-to-ssrn.html

  48. hell Ohad,

    Morphosys has had a nice run lately, now at 1 billion eur. Do you consider taking profits?

    thanks

  49. Not for the time being. They are diversified and cash flow positive with a lot of upside.
    I would sell only if MOR202 data are disappointing.

    Ohad

  50. Hi Ohad,
    Array have started their PIII for MEK162.
    What is the probability that MEK162 receives approval in any indication?
    What is the commercial potential?
    Array is now worth $ 550 million on the stock market. What value should be assumed for MEK162 alone? Maybe 300 Mio. or more? Array looks pretty cheap for me.
    Thanks.

  51. Astra Zeneca think arrays selumetnib could be a billion dollar market and if 520 makes it with onxx kyprolis then that could be big…danopevir(hepc) and pain drug 797 are not going to make it…jmho

  52. Thanks Kirk
    After your explanation (I was not aware of the “Revlon” duties) I feel better to keep ONXX.
    –andre–

  53. Agree, ARRY is very cheap if you factor in the number of programs at the various stages. I will touch on that and the deal with ONTY on the next post on Sunday.
    MEK162, in the hands of NVS and with the co-promotion rights should be worth at least 150M, Selumetinib even more because of the p2 proof of concept in NSCLC.

    Ohad

  54. Agree on all except 797. There is still value in a non-opioid drug which despite the safety issues . (opioids carry a heavy load of toxicities and addiction issues).

    Ohad

  55. P2 asthma data for ARRY-502 should be out any time now. Squarer has seemed pretty upbeat about the potential but it’s very hard to handicap this trial since there’s really nothing to go off of. Also, this class of drug (CRTh2) has already failed before, though ARRY thinks they are testing the drug in a better patient population (mild to moderate asthma) where they can show a benefit. We should see shortly. I’m skeptical but I also think 502 is essentially a free shot on goal as I don’t think the market has really priced in success here. In any event, I’m long for 520, 614, and the MEKs.

  56. Hi Ohad,

    Congrats on ONXX. Do you have an opinion on 4SC? Seems like the market cap is low, and with a couple interesting programs. Thanks!

  57. Care, never heard of 4SC before myself so took a look. Looks like sub-$100M mkt cap, just over year of cash left, and primarily focused on their HDAC (resminostat) for front-line HCC (sounds like next step for that is P2b trial per recent CC). 4SC seems to have direct relevance to ARQL and EXEL though they are going after a completely different line in front line than 2nd line. In recent CC, they said reason to test in front-line to try to show benefit in combo w/sorafenib (not just against sorafenib) was due to competition in 2nd line. Have to think trying to show benefit in front-line a much bigger hurdle. Also, not clear how convincing prior HCC data was for resminostat since I think they just tested drug as monotherapy and in combo w/sorafenib w/o control of sorafenib+placebo. Not sure what we can read into that. Interesting that 4SC thinks they have a biomarker for future HCC trials in zinc finger protein 64. Question is if that’s just a post-hoc fluke or if it’s a real signal.

  58. CLDX up 14% today. I dont see how the market cap of that company can be close to $2B. I know you own it, but that valuation is outrageous. On their phase 2 data, I thought the sample size was quite small. I dont see how wall st can assume that P3 is a success. The glioblastoma study is a ways out as well. Sometimes I feel they are easy shorts then I look at PCYC.

  59. Hi Ohad,

    what do you think about Immunomedics? I think they have a quite interesting pipline and a small market cap. Maybe a stock to watch and to buy after a pullback?

    Thanks for your opinion!

  60. Thanks, Care.
    I am not very familiar with them. The lead program (HDACi) belongs to a problematic class of drugs. Epigenetic drug development is moving to other target classes (HMT, BRDs etc.) or selective HDAC inhibitors (HDAC 2 and 6 , in particular).
    The inflammation program is intriguing, though, will try to learn more about it.

    Ohad

  61. I am a fan of both of CLDX’s lead programs and believe they have great scientific capabilities. Still, I admit, it is hard for me to explain the current valuation, given the fact results are expected only in the 2014-2015 timeframe.
    2 potential explanations might be the CD27 program and the initiation of DDD trial.

    As you wrote, I often underestimate how generous the market can be when a company has exciting products. I got out of PCYC too early but in that case activity as monotherapy was unequivocal and spectacular.

    Ohad

  62. I am checking up on them every once in a while. They don’t have a stellar track record but I think epratuzumab has a reasonable chance of success in lupus. Benlysta’s lukewarm launch is an overhang but epratuzumab might be more potent and its p3 looks better designed.

    Their Trop2 ADC has some intriguing efficacy signals but I would like to see the complete data in a peer reviewed journal or a medical conference.

    Ohad

  63. Ohad, what’s the concern about pan-HDAC, as opposed to selective against HDAC 2 and 6 specifically? Is it a safety margin issue with pan vs selective? I ask in reference to CRIS’ CUDC-907, which they call a pan-HDAC inhibitor and PI3K inhibitor (primarily alpha and delta). Per recent poster (http://www.curis.com/CUDC_907_AACR_2012.pdf ), looks like 907 is most selective for 1, 2, 3, 6, 10, and 11 and very unselective for 4, 5, 7, 8, 9. Would you be concerned here with 907 given this profile? CRIS is pursuing MM, among other heme onc indications.

  64. Ohad,

    Don’t forget about Cramer’s recommendation of CLDX as a good speculative play about a month ago. LOLOL Actually, his analysis was surprisingly good. He knew the pipeline quite well. Personally, I think CLDX’s rise has to do with the Amgen bid for ONXX, although the relationship between the two events is not quite logical.

    An oncologist that I know thinks that if data is positive on CDX-1127–readout on solid tumors this year and hematological malignancies in early 2014–it will be perceived a a complement to the PD-1 inhibitors. If that’s the Market perception, then the SP will really fly.

    Let’s see how the bids for ONXX play out and how CLDX’s SP responds to that scenario.

    BTW, do you have any thoughts on the Oncomed IPO? The management team certainly looks impressive. What do you think of the science?

  65. Ohad

    U should do a line by line itemized breakdown for Array on the potential market on each program… starting from greatest to least and then handicap their potential outcome…lol…just wishful thinking…this and EXEL r my babies :)

  66. Yes the issue with broad spectrum HDAC inhibitors is safety margins. HDACs are involved in so many processes that it appears hard to have a therapeutic window. PI3K inhibitors share the same problem, which makes me a bit concerned about 907 but let’s wait to see the data.

    Ohad

  67. CLDX has always been a strong immunotherapy player, maybe it’s enjoying the PD1 festival.

    Oncomed is very impressive, one of the first to realize the potential of CSC. Although they haven’t shown anything exciting in the clinic their pipeline is impressive. They had an interesting publication recently about patient selection biomarkers for their notch program.

    One disadvantage of their antibodies is that CSC drugs should not have a clear tumor shrinkage signal so longer larger trials are needed.

    Ohad

  68. Thanks Ohad, agreed, I am not psyched they are channeling most of their resources into the HDAC + sorafenib trials. The inflamm program caught my eye, but I can’t find too many details.

  69. Thanks mc, great analysis. Imagine the stock could jump if they get a partner, but who ‘s looking for pan HDACs? Will follow for a bit to see if they provide more info on their preclinical stuff

  70. Ohad,
    Many thanks on all the great work you do, I can honestly say your site is an unmatched source of information and analysis.
    Thoughts on today’s SNTA fast track news given the post ASCO volatility?
    thanks
    Jeff

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