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. 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

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  2. 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

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  3. 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

    Like

  4. 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–

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  5. 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

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  6. 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

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  7. 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.

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  8. 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

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  9. 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.

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  10. 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.

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  11. 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

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  12. 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.

    Like

  13. 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.

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  14. 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

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  15. 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

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  16. 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?

    Like

  17. 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

    Like

  18. 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

    Like

  19. 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

    Like

  20. 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

    Like

  21. 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

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  22. 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

    Like

  23. 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

    Like

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