Array gets binimetinib back (phenomenal deal terms)

After months of uncertainty regarding the fate of binimetinib, Array (ARRY) announced it regained full rights for the drug from Novartis (NVS). Binimetinib (MEK162) was originally partnered with Novartis in 2010 (discussed here) and has been aggressively pursued since. Novartis had to return binimetinib back following the acquisition of GSK’s (GSK) oncology portfolio which included Mekinist, a MEK inhibitor approved for melanoma. Although binimetnib has a high likelihood of returning to Array, the decision is still subject to final approvals for the GSK-Novartis deal.

Surprisingly favorable deal terms

Deal terms are extremely positive as they provide Array with a significant upfront payment (up to $85M), transfer of all the relevant regulatory and IP materials, and significant future funding for ongoing P3 trials.

The biggest surprise was Novartis’ commitment to supply some of its investigational drugs that are in ongoing combination studies with binimetinib. Moreover, Novartis will provide the compounds to Array should the combinations reach phase III trials. Preliminary results for two of these combination studies were presented at ASCO and provided intriguing efficacy signals (see abstracts for combination trials with LEE011 and BYL719).

This has important implications as it will allow Array to stay competitive in the crowded MEK arena. Without Novartis’ commitment, Array would have had to get similar drugs via collaborations with other companies, which could have created a 2-year delay in development timelines (need to do phase I portions again). It also eases some of the pressure to find a partner for binimetinib.

Interest in MEK inhibitors is at its peak

Getting binimetinib back is great news for Array, which will transform to a phase III company on the verge of commercialization. Binimetinib is being studied in three pivotal trials (melanoma and ovarian cancer) as well as multiple phase II studies (see figure below).

BinimetinibSource: Array Biopharma presentation, April 2014

MEK inhibitors went in and out of favor, but are now emerging as promising drugs, especially for tumors with mutations in the MAPK pathway (RAS-RAF-MEK). Array has the broadest exposure to the MEK opportunity as the only company with exposure to two MEK inhibitors: Binimetinib and selumetinib (partnered with AstraZeneca[AZN]). It is also important to note GDC-0994, an ERK inhibitor partnered with Genentech. ERK is downstream of MEK and may open up new opportunities in tumors with dysregulated MAPK pathway.

The initial wave of clinical data (2008-2011) with MEK inhibitors has been disappointing. As monotherapy, MEK inhibitors demonstrated limited efficacy and dosing was limited by side effects (especially skin and hematological toxicities). In recent years, the outlook for MEK inhibitors has gradually improved following promising clinical data across multiple indications, driven by rational combinations and accurate patient selection.

The strongest validation for MEK inhibitors is obviously in BRAF+ melanoma, where two different MEK inhibitors (from GSK and Roche, respectively) led to a significant increase in overall survival when added to a BRAF inhibitor (See publications here and here).  Other trials demonstrated promising signals of activity in lung, colon and ovarian cancers with BRAF or RAS mutations. A new and exciting approach is combining MEK inhibitors with PD-1 antibodies, pursued by Roche (with Exelixis’ MEK inhibitor).

MEK+PD-L1Roche analyst event, ASCO 2014

Imminent fundraising, licensing deal

By regaining rights for binimetinib, Array finds itself in an unusual position. One the one hand, it has a drug that requires a massive infrastructure and ~$200M in development costs over the next 2-3 years (on top of the funds received from Novartis). On the other, it has under $100M in cash and a debt of ~$100M (before receiving any funds from Novartis). Therefore, the most important question going forward is how Array chooses to fund binimetinib’s clinical development.

In the very near future, Array will likely raise money in order to provide financial stability and remove the liquidity overhang. The next step would be a new licensing deal for binimetinib which will enable Array to offset some of the cost as well as pursue additional combination regimens. Array does not have a lot of options given the large number of MEK inhibitors in the clinic (From Roche, AstraZeneca, Novartis, Bayer and Merck Serono). Potential partners are global companies (Array will probably keep some US rights) with interest in late stage oncology assets. These include Pfizer (PFE) (who had a 1st gen MEK inhibitor and was interested selumetinib as part of the Astra bid), Merck (MRK) (PD-1 combinations in lung and colon) and Lilly (LLY) (MEK inhibitors can complement Erbitux in KRAS+ colon cancer).

81 thoughts on “Array gets binimetinib back (phenomenal deal terms)

  1. Hi Ohad,

    Thanks – nice analysis! A few questions though for you and the other readers of this blog. Although it great to get a asset back in the middle of multiple phase 3 trials how beneficial is this really??
    In braf melanoma, they’d be 3rd to the party – maybe survival curve can differentiate them from Novartis and Roche but if not that seems like a uphill battle. And this isn’t even mentioning how they get access to the NVS brafi (lgx818). In nras melanoma, it is a much smaller opportunity than braf and targeted therapy in nras has not shown the “heady” ORRs like braf indication (ie brafi + meki) which makes it vulnerable to i/o agents (or not?). I am not very familar with low grade serious ovarian cancer to comment on this “bucket”.
    Where binimetinib has better prospects (at least in my opinion) is in combo with cdk4/6 in nras (and maybe PIKa solid tumors) BUT on the call they said they’ve have access to these compounds. They wouldn’t elaborate on what “access”: means but once commericalized what would deal terms look like for cdk drug as an example. Interested to hear your and others thoughts on this.

    thanks,

    Mike

  2. Mike – Thanks. I agree that there are still a lot of variables regarding competition and market opportunity. The BRAF+ melanoma will be hard to penetrate, especially if LGX818 will go to another company. NRAS+ melanoma is less competitive but modest in terms of commercial opportunity. Serous ovarian cancer is also quite small.
    Still, MEK inhibitors have a lot of potential in additional indications where efficacy to date has been encouraging and commercial opportunity is significant (KRAS+ NSCLC, BRAF/KRAS CRC etc.).
    I think “access” is what they need. Upon approval, NVS will be able to sell its drugs (LEE001, BYL719) and book revenues. Don’t see an issue there.

    Ohad

  3. Hey Ohad
    thanks for your thourough analysis on the ARRY deal.
    From what you have written, I’m guessing you will wait until the next round of financing to add more shares? But ARRY has 100M in cash and anotehr 85M is coming in, do they really need to raise more money? You mention they might partner the drug, which might bring in more money still?
    Sandor, that ex-incyte executive who joined ARRY recently made a good move, it seems, and timed it right.
    Dan

  4. Dan – IMO they must raise cash immediately especially given the good sentiment towards biotech on the street (nobody knows if and when this will change…).
    As a company, you can’t seriously pursue a drug like binimetinib without having a significant cushion of cash to rely on. Potential partners might also use ARRY’s weak cash position to in negotiations. Therefore, the right scenario would be, raising 100M now, partner the drug is 6 month time and launch new p3 trials in 2015.
    The fact Sandor joined ARRY from INCY is a very good indication, no doubt. Whether he made the right choice remains to be seen.

    Ohad

  5. hi Ohad

    this partial clinical hold for ESPR’s ETC1002 since 2009 because of PPAR-like properties, how risky do you see that?

    best regards
    Christian

  6. Ohad
    do you plan to write about the ASH meeting?
    Are concerned about lack of OS with Adcetris. Also it looks that SGEN will have serious competition in the future from MRK and BMY.
    thanks — andre–

  7. Ohad,

    regarding cd38 mabs you mentionned that you are less excited now than before. for what reasons actually? duration of response, or falling response rates compared to initial findings, or other reasons?

    Celg/Mor want to differentiate their mab by combining with Pomalyst – does it make sense to you somehow compared to other combination partners?

    thanks!

  8. Hello Ohad, MorphoSys and Xencor published final results from phase 1/2a trial of MOR208 (XmAb5574) in CLL/SLL at ASH. Are these results a confirmation of your previous opinion (there are more promising agents in clinical development)? Thanks.

  9. I think there is more promise for MOR208 in NHL indications, see eg fast track designation in DLBCL (which is as I understood is both “medical-need” as well as “promising-but-early-data” driven). so i think it will be interesting to see updated results on this study later this weekend.

  10. Christian – if you are referring to the long term carcinogenicity study that should be completed, so far results look clean but there is always risk in such experiments.

    Andre -will try to write something about ASH, still not sure I’ll have the time. I thought the AETHERA data were solid and should lead to approval even without an OS benefit. Will be interesting to see long term remissions as potential cures. Agree about PD1 as potential competitors but results are early and nivo’s response rate may overstate the effect in subsequent trials (keytruda’s numbers were less impressive). Down the road using Adcetris+PD1 may be ideal. Short term, the overhang is there, though.

    Christian – CD38 antibodies look good but their efficacy (response and durability) are less impressive than expected. Pomalyst is an approved drug so theoretically any company can use it.

    Toby – yes, no change there umo.

    Christian- fast track indication does not imply results are good. Perhaps in combination with other agents (cd20, btk, bcl2) CD19 mAbs will become standard of care.

    Ohad

  11. Hi Ohad,

    yes sure, Fast Track Designation does not imply that results are good, but for FTD, a company must have clinical or non-clinical data to demonstrate the potential to address the unmet medical need. also, the disease must be a serious one.

    nice short overview on the different expedited FDA programs here on page 11
    http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM358301.pdf

    = = = = =

    by the way, do you have any short comments on the MOR208 data releases for CLL/SLL and for NHL-subtypes this weekend?

    what would be a good response rate for example for DLBCL?

    thanks!
    Christian

  12. hi Ohad

    TGTX seems to have interesting stuff (some buzz az ASH as I noted on twitter). have you looked at them? maybe also KPTI (drug selinexor) that you have looked at?

    what do you think about all the CAR-T developments (Juno, Kite, Cellectis etc.) – everything to expensive already? CAR-T tech seems quite revolutionary, but disadvantages to other approaches (mabs etc) could be complicated handling and side-effects profile?

    BLUE wow today, up in the sky…

    thanks as always
    Christian

  13. Christian – MOR208 clearly has some activity in NHL/CLL but the field is getting crowded and differentiation may be tough. In DLBCL, a response rate of 30% in a durability of responsr of 6 months is considered sufficient.

    Re TGTX and KPTI still didnt have a chance to look at the data thoroughly (on vacation). BLUE’s data are phenomenal, bodes well for other genetic diseases that may be amenable to gene therapy.

    Ohad

  14. Ohad, enjoy your Holiday!
    BLUE data will increase the confidence in the gene therapy.There are 3 companies which may profit from the change in the sentiment – CLDN, AAVL and QURE.

    CLDN in particular looks very interesting – breakthrough designation, Phase II data in April with endpoints easy to achieve: Risk Reduction of 45%, HR 0.55, while they had in Phase I with one year data RR 88%, HR 0.12 at p=0.003.
    Based on the BTD and relatively large Ph II trail (250 pts.) they may ask for accelerated approval with the Phase II data.
    It is still $370M even after the run in the last several days.

    AAVL has the potential to generate similar excitement as BLUE since they can completely cure WMD with a single injection, but they are very early in the development.

    QURE has the only one gene therapy already approved in EU, looking for FDA approval.
    Do you have an opinion about these companies?
    thanks — andre–

  15. Hello Ohad, great news for Array and ONTY: ONT-380 news at San Antonio Breast Cancer Symposium. What is your opinion? Thanks.

  16. andre – Agree, this looks like the beginning of gene therapy’s golden age, with the caveat of limited follow up for safety (especially carcinogenicity). Of the 3 you mentioned I like AAVL best, given the huge commercial opportunity and the potential beyond VEGF as a target. 2 additional companies with gene therapies for eye diseases are AGTC and Spark.

    Toby – Don’t know if I would call the news “great”, results are preliminary and it’s hard to distinguish ONT380’s activity. The 20M ARRY got for their rights in the drug are nice but are almost irrelevant relatively to the money in needs for binimetinib.

    Ohad

  17. Hi Ohad,
    Any thoughts on the approaches between AAVL and AGTC? Any reason why QURE is at the bottom of your list. Thank you.

  18. Ohad,
    You are right about AAVL having the largest commercial opportunity, but CLDN is closer to the goal. With break breakthrough designation and oversized Ph 2 they may apply for NDA already in 2015 (Ph 2 data in April).
    Any thought on ZFGN? They seams to have a unique approach to severe obesity – adjust metabolism by inhibiting MetAP2 enzyme. It does not look expensive for company with Ph 3 trail in Prader-Willi syndrome for which there is no approved drug.
    thanks — andre–

  19. mike – I am still studying the field. Both AGTC and AAVL use AAV as vectors for their ophthalmology programs. AGTC’s initial focus is on rare genetic diseases (XLRS, ACHM) while AAVL is initially going after the huge wet AMD market. AAVL also has preliminary clinical proof of concept whereas AGTC will have clinical data next year.

    Didn’t write about Affimed. They have a neat platform but I don’t like their lead program, not that efficacious imo.

    Chris – As I previously wrote, way too expensive in light of their clinical data.

    andre – Agree about ZFGN, very interesting story and valuation is not that high.

    Ohad

  20. Alex

    as I understood they will have data inhouse late 2014, publication then early q1 next year

  21. Ohad

    have you had time to check TGTX and KPTI ASH updates?

    TGTX seems to have a best-in-class PI3K, mainly differentiated by the clean safety profile.

    KPTI, what do you think of Selinexor? quite bit a sell-off after ASH

    thanks
    Christian

  22. Hi Ohad,
    I appreciate all the comments you provide on the blog.
    Any thoughts on CALA? They are being touted as mini AGIO.

    Peter

  23. Alex – right, ACLF top line data should come first early next year followed by POLT-HCV-SVR p2b later in the year (thanks, Christian).

    Christian – Re: TGTX, the drug works but I am still no convinced about its differentiation from similar drugs (INFI). Re: KPTI, numbers are still very small (n=10) but it seems unlikely that the activity they see is solely due to dexamethasone. Safety is a major issue as well. Bottom line, both are still too expensive imo.

    Peter – Incredible price action for CALA, I admit I never thought it could get this high without actual clinical data. Having AGIO as a benchmark clearly helps although they target different mechanisms in cancer metabolism. The only positive thing I saw from them is the ability to inhibit glutaminase in tumor biopsies post dosing but I don’t know if this eventually leads to anti-tumor activity.

    Ohad

  24. Ohad
    Any idea why ESPR has been removed from the NASDAQ biotech index?!?
    The announcement reads: “As a result of the re-ranking, the following eight securities will be removed from the Index: … Esperion Therapeutics…”
    I checked the eligibility criteria for re-ranking:
    “minimum market capitalization (>200M), average daily trading volume (>100K shares), not in bankruptcy, not in BO procedures, no withdrawn audit opinion,,..”
    I do not see anything wrong with ESPR stock with respect to the listed criteria?!?

    The annual re-ranking will become effective on Dec 22. Probably some bio index oriented funds will sell ESPR. Is it significant or no event for the stock?

    thanks–andre–

  25. andre – That’s strange… usually the companies that are removed are less successful which have had bad announcements and price depreciation (Rigel, Onconova, Amarin etc.). I don’t understand why they took ESPR out, if you look at the list of companies that joined the index you’ll see there is an abundance of good smid cap biotechs.

    Ohad

  26. Hi Ohad,
    Any thoughts on BIND? After two seemingly positive news items, Merck agreement and P-II data on BIND-014, the stock has dropped like a rock. From what I can tell they have good cash on hand. Particularly interested in you thoughts on the platform and pipeline.
    Thanks as always for your insights and the time and effort you put into this site.
    Jeff

  27. Ohad, even more annoying about ESPR de-listings is that stock like RTRX is joining the index while simultaneously receiving a notice for non compliance with NASDAQ. They published on Dec 15 the most ridiculous 8-k:

    Item 3.01 Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; … Nasdaq has determined that the Company has failed to comply with the shareholder approval requirement of Nasdaq Listing Rule 5635(c)

    Item 7.01 Regulation FD Disclosure.
    The Company was informed that it will be added to the Nasdaq Biotechnology Index effective prior to market open on Monday, December 22, 2014

    What a joke!!

  28. Alex – Not familiar with them.

    Jeff – BIND’s technology and approach are scientifically interesting but to date their lead program does not appear differentiated efficacy-wise from Taxotere. The earlier stage programs are more exciting but will take time to reach proof of concept.

    andre/Chris – In any case, there doesn’t seem to be a major impact.

    Ohad

  29. Ohad, what did you think of ONTY’s results announced at SABC? Kirkman must be happy with them, because he did a further licensing deal on the drug with ARRY. My concern here is with the finances. Even before the new deal, the finances were shaky, and they were guiding for only one more year of cash. ONTY already has 92 million shares outstanding (not fully diluted) and further dilution at this price will be horrible. They really need to partner. I’m not sure Kirkman is much of a CEO. Another Seattle company, DNDN, tried to go it alone in oncology and we know what happened to them. Puma now has a market cap of $6 billion!!! I realize ONT-380 is far behind neratinib, but is it $6 billion behind? You have written positively about ONT-380 before, so I’m wondering if that is still your opinion. Would you be a buyer here?

  30. Richard – I though the ONT380 data were OK with some interesting signals but too immature to reach any meaningful conclusions. ONT380 is not just behind neratinib in terms of development stage, it may also be less effective as a reversible selective HER2 inhibitor (vs. neratinib which is an irreversible EGFR/HER2 inhibitor).
    I prefer the exposure ARRY provides over investing directly in ONTY.

    mike – bispecific antibodies generated a lot of noise but it remains to be seen if they deliver on their promise. I like Genmab’s and MGNX’ platforms, they are robust proven platforms and in Genmab’s case they have a native IgG format.

    Ohad

  31. hi Ohad

    IMGN exhaling a lot.

    any thoughts about it from here with its new valuation?

    thanks
    Christian

  32. Far from being an expert by my feeling is that they missed the gene editing train with better technologies (CRISPR) expected to replace their zinc finger technology.

    Ohad

  33. Hi Ohad,

    ADC stuff

    Seems like bad news today for IMGN on the MARIANNE data. I know you like the stock so is this an opportunity while the shorts jump ship?

    Also on SGEN – saw an interesting perspective in seeking alpha today on them http://seekingalpha.com/article/2767275-seattle-genetics-good-tech-but-on-the-wrong-path – i know you still hold lots so do you agree with long terms challenges in light of competition on moderate AETHERA results.

    James

  34. Hey Ohad
    great debut for JUNO today, up almost 60%. I wonder what you take is on teh CART field given the high valuations. Also, what companies are leading CRISPR? Or is it just too early? JnJ recently partnered with Transposagen. One interesting thing, similar to BLUE, is that there is the thinking that drug development could be cut by a significant number of years (I read that CRISPR therapies could be developed and borught to market in 3 years)
    Thanks
    Dan

  35. regarding CAR-T companies, Cellectis from France, do you have any opinion Ohad? impresssive deals, though pfizer maybe not the smartest?

    CAR-T seems very promising but right now overhyped to me.

    bought some Cellectis to have some exposure, but for JUNO et al., seems everbody looking at it right now, so maybe not a good time for entry? there will be setbacks for CAR-T companies for sure….

  36. Hi folks, regarding CAR-T Ohad wrote in November:

    “Ohad Hammer on November 17, 2014 at 11:07 am said:

    James – I prefer not to comment on the CAR space as the fund I work for (Pontifax) is one of KITE’s founders.”

  37. Ohad
    This year was very challenging for the ADC stock. Both main players performed very bad – SGEN – 18% and IMGN -58%, compared to IBB +38%. What is even more disturbing, their proprietary pipeline is just burning money without any meaningful progress. The outlook for 2015 for both company is grim.
    Do you see any hope for these companies or the game is over for the ADC technology.

  38. hi Ohad,

    what do you think about Sorrento after this announcement with Patrick Soon-Shiong / NANT?

    somehow I have the impression that Sorrento is throwing arount with a lot of popular words like CAR-T, ADCs, PD1 etc. antibodies etc… they basically claim they do everything – which seems impossible for such a small company.

  39. Ohad, another question.

    more and more media report about the hugely increasing problem of antibiotic resistance, and that it will cause millions of casualties within the next few decades.

    two companies i know that are still “available” (after Trius-acquisition by Cubist, and Cubist-acquisition by Merck) are Achaogen and Cempra. both are having hefty share appreciations right now.

    have you looked at this field? what opportunities do you see to financially benefit from this trend? (e.g. MRSA drug developpers, etc.?)

    thanks as always,
    Christian

  40. Hello
    anyone here invested in CANF ?
    pontifax not invested in it , Ohad can u share your thoughts on it?

    why the stock isnt listed directly on google finance?

    Thanks
    Alex

  41. James –
    The MARIANNE news are very surprising… I prefer to wait for more data with IMGN’s proprietary programs before getting back in. In contrast to the market, I thought the AETHERA data were solid and bode well for improved cure rate and 1st line results (still far away). Regarding competition from PD-1 antibodies, there is risk for Adcteris from that direction but it isn’t high imo as PD-1 abs are many years behind Adcteris and activity in larger populations may not be as high as initially. Lastly, a combination of Adcteris+PD-1 may be a transformational in HL, where cure is an achievable goal.

    Dan/Chris/Christian – Sorry, prefer not to discuss the CAR space. (Thanks Hubert!)

    andre – I share your view of the ADC space… In contrast to what I hoped, Adcetris and Kadcyla are the exception rather than the rule. Don’t forget that a lot of fields took time to mature so perhaps new technologies will be able to realize the potential better (e.g. SGN33A, which appears to have a good efficacy/safety profile so far.) I still think there might be 2-3 good ADCs from SGEN and/or IMGN.

    Christian – That’s my impression as well although I don’t know SRNE very well.

    Alex – Sorry. Can’t discuss Israeli companies.

    Ohad

  42. Hi Ohad

    regarding previous antibiotics posting, TTPH tetraphase is anothet name i forgot.

    you have any opinion on those companies and this market segment?

    thanks!
    Christian

  43. Ohad
    About BLCM. We understand your reluctance to discuss CAR-T space, but I would appreciate if you share your opinion about their CID technology – CaspaCIDe and DeCIDe. It will be understandable if you do not talk about CAR related projects – CIDeCAR and GoCAR-T.
    Is it something valuable or just a fancy names?
    thanks — andre–

  44. Christian – Unfortunately anti-infectives is in an area I am familiar with but I agree that novel agents are desperately needed. PTCT’s gram- negative antibiotics looks pretty good imo.

    andre – prefer not to comment, sorry….

    Ohad

  45. Hi Ohad

    Quite an impressive deal JNJ (Janssen) signed with MacroGenics on their preclinical CD19 * CD3 DART (MGD011). Have you seen the data presented at ASH this year ?

    I think bispecifics get a lot of attention theese days !!

    Regards
    Sukkeralf

  46. Christian – I am also invested in Cellectis (ALCLS.PA) in the CAR-T space. Shares trade at a sharp discount to all the other CAR-T players that get the headlines and Cellectis could wind up with the most disruptive approach (off-the-shelf) if it pans out in the clinic. There are of course plenty of risks and no guarantee the approach will work in the clinic but at the sharp discount to its peers, I’m willing to take a small gamble. I’d be surprised if investors in the other CAR-T players don’t have at least some exposure to Cellectis as a hedge on their CAR-T holdings provided the approach pans out in the clinic. Similarly, if Cellectis approach does fail in the clinic, the other players may well wind up big winners so I am considering a position in other players as well to effectively hedge my ALCLS.PA holding.

  47. Sukkeralf – Indeed very nice deal for MGNX for a preclinical program in a highly competitive segment. Their ASH data were very good, in vitro they show a higher potency than AMGN’s blinatumomab but hard to predict if this will translates to advantage in patients. One major differentiator is their format (Fc fusion) which may allow weekly dosing vs. continuous dosing with Bmab.

    Ohad

  48. Mike, Ohad wrote on November 24, 2014:
    Chris (MRTX) – My main concern about their drugs is lack of selectivity which will make it challenging for them to reach deep and durable inhibition of Axl and MET.

  49. Ohad, could you write something about why you like SAGE? What do you think about MRNS? Marinus may have a better drug and it has one-tenth the market cap of SAGE. However, with only four employees, MRNS is a virtual biotech.

  50. Mike – As they still haven’t proven good efficacy in the relevant subsets (MET/Axl+ NSCLC) and it’s unclear whether they can reach sufficient target inhibition (thanks, Chris).

    Richard – I plan to touch SAGE and MRNS on my 2014 summary post (just need to find the time for it…). The main difference between SAGE and MRNS is the indication each company is pursuing and the remarkable efficacy SAGE has in SRSE vs. the milder efficacy MRNS reported in epilepsy.

    Ohad

  51. Ohad
    FPRX. Several months ago you said “The immuno-oncology programs are interesting but early, couldn’t find additional exciting stuff in their pipeline”
    Does resent collaboration with BMY in CSF1R – PD-1 combo make them more attractive?
    They will start six Phase 1a/1b clinical trial in NSCLC), melanoma, head and neck cancer, pancreatic cancer, colorectal cancer and malignant glioma. FPRX will conduct the trials and BMY will pay for them – looks a good arrangement for them.

  52. Merry Xmas and Happy New Year to Ohad and all here. Hope to have a great 2015 ! Thanks for your help always.

  53. Ohad, merry Christmas. What do you think is happening with Arql stock price? Quarterly report was good, the stock price begin to upside and then down again.

  54. andre – The approach of inhibiting tumor associated macrophages is very interesting but it needs to be validated in patients. Agree, the arrangement with BMS is attractive.

    Mike – Thanks, Mike. Have a great 2015.

    Luis – ARQL is still penalized for tivantinib and interest in the Akt program is low. I think what we see are fluctuations that don’t mean a lot until the market gets more visibility on pipeline.

    Ohad

  55. hi Ohad,

    what do you think about this concern regarding $CNAT? (I copied some tweets).
    thanks as always
    Christian

    @avidresearch Believe me I am. I’m a liver doc. This company is whacko.

    @karmaswimswami so all the clinical data published so far at http://www.conatuspharma.com/publications/resources.htm … all whacko??

    @karmaswimswami seriously interested in knowing ur concerns with their MOA. Cck18 they keep using is not reliable marker for Apoptosis?

    @avidresearch You’re presuming preventing hepatocyte apoptosis is a good thing. It is most definitely not desirable. Wouldn’t touch it.

    @karmaswimswami theoretical concern?

    @avidresearch W. Wen et al., Hepatology, vol. 55, pp. 1787–1798, 2012. And many other studies.

    @karmaswimswami thanks!!

    @avidresearch In all serious, the smart people in liver are not behind this CNAT and emrica. Be careful.

    @karmaswimswami @avidresearch wouldn’t touch it. Hepatocyte apoptosis just does not make sense. And whenever cells lyse the shed toxins

  56. Ohad,
    Happy New Year.
    Thank you the very informative site. You keep a very high standard in your articles and responses.
    Do you have an opinion about BiTEs technology. I read an opinion that it is the next generation ADC – instead of a warhead it carries immune cells – NK or T.
    I tried to research it a bit and found that a couple of companies are active in this new field – MGNX, XNCR and AFMD. The first two look very well positioned, with multiple collaboration contracts.
    I would appreciate if you discuss this new emerging technology if not in an article, at least in a extended response. My key question is – is it a ground barking technology which will eventually supersede ADC?

  57. Hello Ohad
    Happy new year to you and everybody reading your blog!
    Do you know anything abiut CBAY – they have three programs in phase 2
    Gout and metabolic diseases are their area.
    Thanks for your insight!
    Dan

  58. Christian – Agree there are a lot of uncertainties regarding CNAT’s approach and relevance of cCK18 to chronic live diseases, I still think it’s a reasonable risk reward ratio.

    Steve – I would avoid EXEL until it restructures its debt and/or provide clarity on RET+ NSCLC program. Next Q it might be an interesting bet ahead of the RCC data. I don’t think this clinical trial implies there is a direct collaboration with Genentech since it’s an investigator sponsored trial.

    Richard – I like their technology but not their lead program.

    andre – I believe that eventually both ADCs and BiTEs (or any other bispecific platform) will co-exist, as each approach may have utility in different indications/targets. If I had to pick a name from your list, I would go with MGNX who are already in the clinic with 2 programs against novel targets. Genmab may also emerge as an important player.

    Dan – Sorry, not following them.

    Ohad

  59. Happy New Year Ohad!

    Long-time reader and biotech enthusiast for 30 years, so I have pretty much seen it all. All I can say is that your work is truly top-shelf. Nothing compares.

    Marty

  60. Hey Ohad
    Regarding FMI – what do you think the price point of the diagnostic test will be for the AGIO drug, especially considering that just 15% (If II’m correct) of all patients that will be tested will have the mutation the drugs is targeted to?
    Also, would other companies be able to bring to market knock-off copycat tests for the same mutation? What would stop these company? This threat alone might mean that FMI might have to price the tests very competitively. High prices always bring in competitors. Unless there are patents involved, or other barriers to entry?
    Thanks
    Dan

  61. Marty – Thanks! glad I can help.

    Dan – I don’t think FMI will be able to stop companies who would like to sell NGS-based kits for IDH or any other target. FMI will nevertheless have a clear advantage as the only companion Dx test approved by the FDA for IDH inhibitors (at least initially). They should also have automatic reimbursement. I don’t know for sure what other vendors will have to do in order to sell their tests for IDH, but I assume it wouldn’t be that straightforward.

    Ohad

  62. Steve – No chance whatsoever, both prostate trials failed completely.
    Thanks for sharing these trials, I wasn’t aware of the first one (triple neg breast cancer). Nice to see Roche is putting resources behind cobi beyond melanoma.
    From what I see, both are randomized placebo controlled trials.

    Ohad

  63. Hey Ohad
    What do you think about CAR/TCR technology? like KITE, JUNO, BLUE,AAVL and BLCM. they just have phase 1-2, but market cap is over $2B. what do you think about these companies.

    Thank you,
    Steve

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