Biotech catalysts for 2016

After last week’s pessimistic post, this week I am focusing on potential catalysts in 2016 that could improve sentiment towards biotech as a sector.

As if to remind us late stage trials don’t always fail, last week saw positive news from three different programs, all of which are antibodies in non-oncology indications. Regeneron (REGN) and its partner Sanofi (SNY) announced excellent data in atopic dermatitis, Alder (ALDR) reported positive results in a P2b in migraine and Pfizer (PFE) had positive P3 data for its PCSK9 program.

Below are four additional clinical data readouts that (if positive) may serve as important catalysts.

PCSK9 cardiovascular outcomes trials (CVOT)

Amgen (AMGN) and Regeneron will announce results from CVOT for their respective PCSK9 antibodies. So far, Repatha and Praluent have had weak launches as physicians are reluctant to put patients on injectable drugs without a proven long term benefit (reduction in CV events or death).

I think there is a high (~70%) probability of success for both programs based on dramatic reductions in LDL-C and preliminary pooled analysis from earlier studies.  Positive outcomes data may allow PCSK9 to dramatically improve market penetration in high risk patients who are not adequately controlled by statins with a potential label expansion to other patients with high cholesterol.

Positive outcomes data should be viewed as a positive breakthrough for The Medicines Company (MDCO) and Alnylam (ALNY) which are developing an siRNA targeting PCSK9 with a potentially less frequent treatment regimen.  Results will also be important for Esperion (ESPR) because they will further validate the LDL hypothesis. Compared to PCSK9 antibodies, Esperion’s bempedoic acid has a weaker effect on LDL but as an oral agent that does not cause muscle pain, it may become an important treatment line after statins.

Three high risk readouts – Aduro, Biogen and Lilly

Aduro (ADRO) will report P2b data for its off-the-shelf cancer vaccine in pancreatic cancer by mid-2016. Off- the-shelf cancer vaccines have a terrible track record with many attempts over decades and not a single success (Celldex (CLDX) is the most recent example). The only approved cancer vaccine (Provenge) is an autologous vaccine in which a patient’s cells are taken and modified before re-administration.

An earlier phase 2 trial generated a positive survival benefit of 2.2 months in the overall population and a subset analysis demonstrated a more pronounced survival benefit (5.1 months). The current P2b is designed to corroborate this finding with data expected in the May -June timeframe. Although I don’t think the trial will be successful, positive results will have widespread implications as they will validate the concept of cancer vaccines and set the stage for many other vaccines using Aduro’s platform.

In Q3 of 2016, Biogen (BIIB) will report data from a P2b data evaluating its anti-LINGO antibody in MS. Targeting LINGO represents a new approach in MS, as the drug is designed to induce re-myelination in contrast to available treatments that slow down disease progression by suppressing the immune system. Given the lack of clinical validation for the target and the approach, this program should also be regarded as a high risk bet. In addition, more studies will be required to understand whether anti-LINGO is truly disease modifying and how it fits in the crowded MS market.

Lilly (LLY) is expected to report topline results for its Alzheimer program solanezumab in December 2016 (data may be pushed to early 2017). Solanezumab is an antibody targeting amyloid-beta (Abeta), which like all other Abeta programs, failed to demonstrate clinical benefit in P3 trials. A subset analysis of the failed P3 studies generated a mild signal of activity in early stage patients which was enough to justify initiating another P3. Although market opportunity and unmet need are huge, likelihood of success is low in my opinion given past experience with other Abeta agents. Biogen recently started P3 with its Abeta antibody (adacanumab) in Alzheimer’s disease.

Gene therapy as a potential long term growth driver

So what could be the industry’s next growth engine? To support long term growth, the biotech sector has to expand to new treatment modalities and indications. This makes gene therapy an ideal growth engine given its broad applicability in diseases which are not well addressed with current therapeutic approaches (therapeutic proteins, small molecules, siRNA etc.).

After 20 years of setbacks, gene therapy had a comeback in 2013-2014 based on preliminary results from Bluebird Bio (BLUE), Spark (ONCE)and Avalanche (AAVL), among others. Since then excitement waned following a mixed performance: Sprak reported the first ever positive randomized P3 for its ophthalmic RPE-65 program while Avalanche’s gene therapy for wet- AMD had disappointing results. Bluebird’s Lentiglobin fell somewhere in between, generating a clear proof of concept but only in some patients.

Acknowledging gene therapy’s checkered history, I believe the field is ready for primetime for the following reasons:

Technology – Technologies are mature enough with specialized vectors and delivery technologies that have generated clinical proof of concept across a myriad of indications  (Hematology, ophthalmology, CNS and metabolic disorders)

Pharmaceutical standards – Historically, most gene therapy programs were initiated by research centers. Today, more and more programs are being run by companies according to industry standards and are developed as a pharmaceutical product. This not only removes a lot of regulatory risk but also improves translatability from preliminary clinical anecdotes to late stage clinical trials.

Funding – For the first time, gene therapy programs have sufficient financial backing to reach the market. Between the gene therapy-dedicated companies and their partners, the budget available for gene therapy programs is probably several billions of dollars.

Gene therapy catalysts in 2016

While it is hard to see a single binary event in 2016 for gene therapy, the next 2-3 years will have readouts from dozens of programs across a wide spectrum of indications. (This doesn’t include CARs and TCRs, which are also a form of gene therapy but are regarded as an independent group):

Bluebird Bio remains the most prominent gene therapy company with a focus on hematology. Following a traumatic ASH last year, the company decided to provide another update for its beta-thalassemia and sickle cell disease trials only towards the end of 2016. Based on results to date and plans shared by the company, I am cautiously optimistic about the company’s chances of improving clinical activity.

After announcing positive P3 results for its lead program SPK‐RPE65 in RPE65-related blindness, Spark will file for approval and report initial data for a second ophthalmic program (SPK‐CHM for choroideremia) in the second half of 2016.

AGTC (AGTC) will report initial data for two other rare genetic ophthalmic indications (X-Linked Retinoschisis and Achromatopsia CNGB3) in 2016.

UniQure (QURE) – After presenting preliminary positive data in hemophilia B and Sanfilippo B (a rare neurological disease), UniQure is expected to update on both programs in 2016.

Voyager (VYGR), which focuses on CNS indications, expects to have clinical data for its Parkinson’s program in 2H:16. The program already generated  early signs of clinical efficacy in patients.

Dimension Therapeutics (DMTX), which has a liver targeting vector will have hemophilia B data in 2H:16.

AveXis (AVXS), which completed its IPO earlier this year, will have an update for AVXS-101 in SMA Type 1. The company reported preliminary encouraging results from a phase I study.

REGENXBIO (RGNX) is the most diversified gene therapy company thanks to its licensing agreements with multiple gene therapy companies ( Voyager, Dimension, Baxter and Lysogene). The company expects to advance two programs for HoFH and MPS1 to clinical trials in 2016.

Portfolio holdings – April 3, 2016

Biotech portfolio - Apr 3, 2016biotech etfs - Apr 3, 2016

177 thoughts on “Biotech catalysts for 2016

  1. Thanks very much for the article Ohad. Would you let us know which of the bio’s u like for investing from the above?

  2. Mike – I actually would prefer to go as broad as possible in such a nascent field like gene therapy. I like BLUE and ONCE because their products work (at least in some patients). I also think QURE’s Sanfilippo B program ispromising and AGTC I Iike because they’re very cheap.

    Ohad

  3. hey Ohad,
    what about ABEO – I was not able to determine the technology of their Franconi program which they keep referring as a crispr-based technology– looks a little fishy. They also have sanfilippo programs AAV based
    Thanks
    Dan

  4. Dan (ABEO) – Thanks I wasn’t aware of them. Interesting they are going after sanfilippo A with IV administration. Will add them to my watch list.

    Ohad

  5. Hi Ohad, is there a chance of a bottom in the major biotech indices? The pattern looks like it is but it must be confirmed.
    Or is it just a pre-AACR and pre-ASCO runup and we will see another selloff after…?
    When do you sell your ultrashorts?
    Ville

  6. alex (CLVS) – I think they’ll have a tough ODAC as well as briefing documents. The recent commentary in Annals in Oncology certainly doesn’t help…

    Ville – My guess regarding the correction is as good as anyone else’s. I believe the correction is not over and expect the biotech sector to be weak during the remainder of 2016. My skepticism is based on fundamentals (lack of positive catalysts and biosimilars) and sentiment (Markets usually needs more time to digest corrections and investors sentiment is not low enough to mark the bottom imo).

    Ohad

  7. Hi Ohad,

    The marketcap of CLVS is about 660M and the EV about 420M. Does Rucaparib and Lucitanib alone support this valuation?

    Thanks.

    Rick

  8. rick (CLVS) – Rucaparib clearly has value, especially given the proprietary Dx tool and validation of PARP inhibitors in other indications like prostate cancer. I prefer to wait until uncertainty around rociletinib is cleared before exploring CLVS again.

    Ohad

  9. Hy,
    what’s about Molecular Medicine (MOLMED) based in Milan Italy? Their gene therapy Zalmoxis is waiting for CHMP opinion scheduled on late May 2016.
    Do you know them? If yes, what’s yr. opinion?
    Thks a lot for yr attention

  10. Hello Again Ohad ! I did a search on your site for CTMX, and was unable to find anything.Do you have an opinion on their PROBODY TECHNOLOGY ETC.? Thanks in advance !

  11. Ohad

    You had mentioned LIFE in a positive light on some previous posts.stock has continued to get hit as the bio sector has rebounded nicely in last couple of weeks.with a mkt cap of 75m, are you considering starting a position or will you continue to wait on the sidelines.

  12. Cremino – The ADA-SCID program is exciting and should be approved imo although market opportunity is probably limited. I took a quick look at their pipeline and could not find anything exciting… Antibody-cytokine fusions have not been a success to date and choosing CD44v6 as a CAR target might be problematic based on past experience with the target.

    Bouschka (CTMX) – I like them a lot but the stock is too expensive imo as it does not price in the huge risk translating preclinical findings to humans (especially in the field of “tumor-activated” payloads).

    Dave (LIFE) – Yes I still view LIFE in a positive light and think valuation is very cheap (especially now that they have preliminary clinical data). Very tempting to initiate a position at this stage, the only think keeping me from doing so is my fear that the bio correction isn’t over.

    Ohad

  13. Thks Ohad,
    for yr. attention.
    Ada Scid program got the approval. In my previous post I was referring to Zalmoxis (TK) : a cell-based therapy enabling bone marrow transplants from partially compatible donors, in absence of post-transplant immune-suppression, currently in Phase III in high-risk acute leukaemia and under evaluation by EMA for a Conditional Approval.
    CD44v6: thks. for your opinion.
    Kind regards

  14. Ohad,

    what do you think SGYP? They have already fill the NDA for the plecanatide, recently there are some rumors that SGYP will be acquired.

  15. $EXEL Do you plan to hold on until a couple of quarter of Cometriq sales, and Celestial results come out ? What do you think of the timing of the Cobimetinib label expansion as to when Roche might reveal any label expansions ?

  16. Ohad,

    GNCA got a nice lift from 12-mos follow-up data. Vaccine cos with differentiated technology tend to get acquired — your thoughts on a GNCA take out? Also, have you revised your opinion of TGTX “undifferentiated agents in a competitive market?” My take on TG’s assets for hem cancer is that they’re very competitive re potency, and markedly superior re safety.

    Thanks,
    Mike

  17. Ohad,

    ALDX data from the two mid-stage studies are expected in the second quarter, you know this company?

  18. Hi Ohad

    Do you have an opinion on Epigenomics AG from Germany? They received FDA approval for their blood-based colorectal cancer screening test last week and are the first movers in this field as per my undestanding. Valuation looks still decent.

    Many thanks
    Kevin

  19. Ohad
    LOXO TRK data look good. Do you think they can run fast registration Ph 2?
    Can they get approval for any type of solid tumor as long as it harbors TRK?
    Or it should be tumor specific NDA?

  20. Ohad
    Isn’t it embarrassing to see LOXO doing better than ARRY, when ARRY gave them the TRK gold mine. I guess the ARRY management has to apologize and … resign.

  21. alex (LIFE) – They should have just over $100M right now, which is approximately their market cap.

    Cremino – I prefer to go wit the more innovative engineered programs based on patient-derived cells (CAR,TCR, BLUE etc.).

    Ken (SGYP) – sorry, don’t know them well.

    curiousgeorge (EXEL) – Yes I plan on holding during 2016 as I expect a good label and strong launch (focus on PD-1 failures). Surprised they still didn’t get FDA approval…. Hard to predict reagrding cobi but it’s a high risk wild card, the fact Roche didn’t publish anything so far is not a positive indication.

    Mike Goodman – Re: GNCA, their platform might have utility for neo-epitopes, which could be a reason for a takeout. Not sure what level of validation they have.
    Re TGTX – I haven’t changed my mind. Their drugs work but hard to differentiate them from competition.

    Kenny (ALDX) – Sorry don’t know them well.

    Richard Baker (ARQL) – Still didn’t have a chance to listen. Basically, it’s all about clinical data at ASCO this year and PD markers in Proteus.

    Kevin – Sorry don’t know the field well.

    andre (LOXO) – Yep great data set (also for RXDX). It’s a very good question… My guess is that the FDA will enable to do a basket trial but will limit approval to tumor types where there is evidence in 10-20 pts.

    andre (ARRY) – Agree, it should have been ARRY’s drug…

    Ohad

  22. ARRY is not going away empty-handed.

    BOULDER, Colo., July 10, 2013: “Under the terms of the agreement, Loxo will fund Array’s preclinical research, providing access to Array’s world-class discovery platform and scientists, and will be responsible for target selection and conducting clinical trials. Array is eligible to receive up to $434 million in milestone payments and to receive royalties on sales of any resulting drugs. In further consideration of the rights granted to Loxo under the agreement, Array also received shares of stock in Loxo.”

  23. $EXEL Roche has director level positions supporting the Cobimetinib programs that were brought in as new hires based on the job postings. I think if they did not think it was a meaningful long term bet they would not be investing so much capital in the personnel side. It can be that they want to keep the developments confidential until such time that they think it is advantageous to release the information commercially. Roche could be eyeing to buy Exelixis on the cheap and might not want it’s value to appreciate especially if Cabozantinib turns out to be a good immunomodulator due it’s C-Met regulation.

  24. Ohad, for me the Zalmoxis-(TK)-approach looks similar to BLCMs BPX-501.

    Do you also disregard BPX-501 for more innovative engineered programs (especially BLUE for ß-Thal.) or do you see BPX-501 different?

    If yes, what to make of the higher efficiacy of BPX-501 vs. BLUE. Or would the safety concern superseed efficacy here?

    If no, would you be willing to elaborate a little bid on the difference Zalmoxis-(TK) vs. BLCMs BPX-501

    Thanks,
    SAMi

  25. Toby (ARRY) – Yes, they have some exposure to LOXO but it’s fairly modest.

    curiousgeorge (EXEL) – I always find it hard to interpret these things without real data. If Roche had wanted to buy EXEL, the should have done it already imo.

    SAMi (BLCM) – I like BLCM and the BPX-501 because the data validate their switch technology and the effect is seen after onset of GVHD as opposed to preventative effect which is hard to prove. For me, the real value is in using BLCM’s molecular switches in CARs.

    Ohad

  26. Ohad, what do you think of AFMD?

    Also, what data are you expecting ARQL to present at ASCO?

  27. $EXEL is it possible a small-mid size US oncology company is waiting for approval before acquisition? Said company would not care for EU rights and eventually look to monetize via Japanese partnership for cabo and sell cobi to Roche. Possibly selling rights to Daiichi Sankyo for the out licensed drug. I don’t see anyone paying more than $2.5b plus assumption of debt/convertible.

  28. Richard Baker –
    AFMD – I think they have a solid bisspecific platform but it’s hard to get excited with their lead programs.
    ARQL – I originally expected them to present updates for both Akt and FGFR programs but based on their recent presentation data may come out later in the year.

    curiousgeorge (ARQL) – I thought the presentation was good, still cautiously optimistic about one of their programs moving into pivotal testing.

    Ernie (EXEL) – I don’t think they are waiting for approval to put themselves on the block. In order to get acquired, EXEL will have to show it can generate meaningful sales for cabo in RCC.

    Ohad

  29. BLUE – Hi Ohad, what do you think of the recent data BLUE presented and the way the market responded? I thought the data was promising albeit very early – market responded quite negatively. Could be a sell on the news event and not much more catalysts till ASH? Wonder if it’s worth beginning a position in if it breaks 40.

  30. $EXEL Atezzo plus Cotellic Oral Presentation in ASCO 16, what do you expect the poster presentation TNBC for Cotellic to show ?

  31. Al (BLUE) – Data were good, I guess it’s the lack of data until ASH that keeps investors away. I still like them and plan to add later in the year.

    curiousgeorge (EXEL) – I actually have low expectations from this combination as patients are not biomarker-selected. I am more optimistic about KRAS+ NSCLC etc.

    Ohad

  32. $EXEL Now that we know atezzo plus cobimetinib is an oral presentation for colorectal cancer, do u expect to have similar efficacy for nsclc, and melanoma. I think this is the KRAS mutation you are talking about. I wonder why they are not presenting the NSCLC data yet. Also how big is the colorectal cancer market ?

  33. curiousgeorge (EXEL) – Hard to predict how data will look in CRC. If they see activity (especially in BRAF/KRAS+ tumors) this is very important because monotherapy PD-1 don’t work well in most patients. The market is significant (~50k annual deaths in the US).

  34. $EXEL In ASCO oral presentations generally mean they have good data, they don’t allow an oral presentation for bad data so one can assume based on the standards required for an oral presentation that the data is good.

  35. Cabo approved OS label details

    Table 5. Overall Survival and Objective Response Rate in Study 1 (ITT)
    Endpoint CABOMETYX Everolimus
    N = 330 N = 328
    Median OS (95% CI), months 21.4 (18.7, NE) 16.5 (14.7, 18.8)
    HR (95% CI), p-value1 0.66 (0.53, 0.83), p=0.0003
    Confirmed ORR (partial responses only)
    (95% CI) 17% (13%, 22%) 3% (2%, 6%)
    p-value2 p<0.0001
    1 stratified log-rank test with prior VEGFR-targeting TKI therapy (1 vs 2 or more) and MSKCC
    prognostic criteria for previously treated patients with RCC (0 vs 1 vs 2 or 3) as stratification factors (per
    IVRS data)
    2 chi-squared test

    What do you think 4+ months and 0.66 HR. I am a little confused about details in the analysis.

  36. $EXEL OS data means they are better than Nivo when you can get 4.9 months of OS duration and have patients with brain mets and any prior number of treatments. It means Cabometynx will grab a large share of the 2nd line market and dominate the third line market.

  37. curiousgeorge (EXEL) – I don’t think we can make conclusions at such an early stage regarding the data at ASCO just because of the oral presentation.

    jh/ curiousgeorge – Cabo’s survival numbers are very strong imo, HR (0.66) is better than Opdivo (0.73) which is phenomenal and the 4.9 month difference is clinically meaningful. This should enable EXEL to get a significant market share in 2nd line, not just in PD-1 failures as I originally expected.

    Ohad

  38. Hey Ohad!
    yes, EXEL data impressive. How does it change the valuation? Seems that epicene deal wasn’t that bad after all, considering the high royalties (and p3 data)
    Thanks for this
    Dan

  39. Dan (EXEL) – Well, apparently valuation hasn’t changed much…
    With such an impressive OS benefit, cabo could be a $1B drug and have a strong 1st year launch. IMO, the only thing keeping EXEL from going to 10 is the large debt position which I hope will be repaid after a licensing deal for Japan.

    Ohad

  40. Ohad, given the EXEL long term debt is well in excess of $300mm, its hard to imagine it being paid off with a Japan deal. How much do you expect them to get upfront?

  41. Paul: burn rate is well over 200+/year, so the Ipsen $ is going to be used up over the next year. Unclear how they pay down debt and keep paying $28/y interest expense. Pressure on 1st year sales to bring in the $

  42. Ohad, Cabo a $1B drug only with 2nd/3rd line RCC and MTC? You are kidding, aren’t you?
    With additional indications maybe, but not with the approved indications….

  43. Hi Ohad,

    Any thoughts on CARA therapeutics and its current valuation?

    Thanks,

    Chris

  44. PaulB/Steve (EXEL) – Of the 300M debt I expect EXEL to repay 100M due 2018 (The Deerfield notes) imminently. They can do this with $260M from Ipsen plus 60-70M from an Asian partner. The rest (due 2019) can only be returned after 8/15/16, if the stock is >$6.90. Given the strength of the RCC data, they should minimize cash burn dramatically already in 2016 to ~120M so they should be able to repay at least some of the 2019 notes by year-end.

    Ville (EXEL) – Current global market for 2nd+ RCC is $1.2B and this is achieved with mediocre drugs (no OS benefit) with suboptimal market penetration and (3-4 months of therapy). I expect cabo and PD-1 to dramatically change that as cost per patient will grow 2-fold and number of treated patients will probably grow as well now that patients have real life prolonging options.

    Chris (CARA) – I like them, especially the pruritis program but as far as post surgical pain goes, I am on TRVN’s camp. Still considering owning then later in the year.

    Ohad

  45. FMI

    Hi Ohad, any thoughts on FMI, especially about potential catalysts near-term?

    The company looks attractive at these levels.

    Greetings, n0c

  46. Hi Ohad;

    So ABBV pay $10.2B for Stemcentrx’s Rova-T (ADC technology). Any thought for SGEN’s ADC at this time? I guess SGEN could buyout by AMGN very soon.

    Thank you.

  47. Hi Ohad,

    Any thoughts on IMGN’s modification of Forward I of MS to PIII w/ a PFS end point? I assume they got FDA feedback and were advised to do this over a PII with an ORR end point. It soumds like it will take longer but positive results may be better regarded at the FDA for registration. What are your estimates for chances of success and duration of this trial?

  48. n0cturne (FMI) – Yes, I still think it’s attractive at these levels and hopefully progress in rare NSCLC subsets (Trk, RET, T790M etc.) will provide some tailwinds. The problem is that FMI necame an execution story based on commercial performance without real M&A prospects.

    steve (SGEN) – While it’s hard for me to justify the price paid for Stemcentrx, they had one ADC with good single agent activity in a solid tumor (SCLC). SGEN needs another driver beyobd Adcetris in order to justify a takeout premium.

    Wildbiftek (IMGN) – Didn’t have a chance to listen to the CC but from the press release the decision appears to be data driven so my guess is that response rate is not as high as they hoped for (not even in FR-high tumors). This decreases likelihood of success imo but I need to hear what they say on the call.

    Ohad

  49. After listening to the CC, the confirmed responses in the overall expanded cohort (low, medium, or high expression) is now lower than 30%. They’ve refined the population they’re pursuing to medium and high expressors with three or fewer lines of therapy, a population that according to Charlie Morris whose confirmed responses are “meaningfully higher” than 30% (so I’m assuming < 40%). He has also said that this population will have had prior bevacizumab and will be platinum resistant.

    The results seem a bit worse than the ~50% CRs from last year and because they're now in contention w/ approved agents rather than in pure salvage, they're pursuing a PFS endpoint which will take longer follow-up than just ORR. The bit of good news is that they're comfortable with the safety profile of the agent with the preventive strategies they're using so they're not going to start w/ a dosing ramp up and going with the 3 week schedule. Apparently they haven't met w/ the FDA yet, it seems less likely that they're going get BTD but it's not ruled out. He also mentioned that ASCO data on the 46 cohort from PI will have a PFS readout.

  50. I meant confirmed responses by “CR” above (forgot momentarily about the collision w/ complete response). I think the cash position might not be sufficient for a long PFS based P3 and they may need to do a secondary soonish. In this enriched subpopulation, having to compete w/ other agents in the fourth line might also make the endpoint slightly harder to achieve, but typical responses are 15-20% compared to > 30% and typical PFS is 3.5-4 months and they’re powering for 6 months+.

    From this poster:

    http://www.immunogen.com/application/files/3914/5877/3807/biomarker_AACR_EORTC_Poster_final.pdf

    They seem to be hitting well over 6 months with high expressors (40% of all patients seen) and close to 6 months with medium expressors (20% of all patients seen). ASCO data should give more clarity.

  51. IMGN: It is like OHAD said. ORR is not sufficient enough to do a ORR study – the need 30% or better to achieve breakthrough designation. They only reached below 30% in all patients. What dissappoints me is that the ORR fell from 35% to under 30%, so the new cohort must have response rates of 25% or below. They blame the many lines of therapy of the patients of the extended cohort and want to exclude patients with more than 3 lines of therapy. They haven’t met with the FDA yet. Will do so in summer. And start the trial by end of year if there is no change request by the FDA. The trial will run at least a half year longer than the former planned trial. So a delay of at least 18 months. Very disappointing and again shows how clueless this management is.

  52. Ohad, BLCM is now below $10. You said earlier in the year that you’d be a buyer, if BLCM fell below $10.

  53. IMGN: They did say that ORR for medium/high expressors is “meaningfully above 30%”, but you’re right, it’s likely that the ASCO data will show a substantial decrease in response for even this group in the salvage setting. They were sufficiently spooked to limit patients to no more than 3 prior therapies; according to Morris, this puts them in competition w/ approved agents and hence they needed the more robust PFS endpoint. This does improve their addressable patient population from 2,000 to more like 5-7,000 he mentioned.

    The main concern is that this forces them to raise more money at some point prior to unblinding and their stock is dead money until then. I still think the 853 P3 will be successful though and we’ll probably see some FORWARD II data before long. I’m holding on to my shares for now until I see the ASCO data.

  54. I believe this is just another case where IMGN just shot itself in the foot. If they had never revealed data from the Phase I/II Trial, investors would have been thrilled to learn that the data from a Phase I/II was sufficient to initiate a Phase III.

    Certainly, they got excited about early data and thought a registrational Phase II would be in the cards, and they told us so. I really wish I knew why the data in Phase I’s often is better than what’s seen in Phase III, perhaps clinicians looking for early success select patients for the trial more likely to be helped, I don’t know this to be the case, but it’s not uncommon for early results to yield over optimism.

    It’s my belief that IMGN now knows what it has, and as long as the FDA agrees with what they want to do with Phase III, it should lead to success for a much larger target market. As for funding, with the timing and duration of the upcoming trial I believe we’ll see substantially more in both milestone payments from partners who’s drugs are advancing to later stage trials, or entering the clinic. I also believe that with sales growth, both milestones and the restart of royalty payments from Kadcyla sales will start to kick in. I’m not saying IMGN won’t need to dilute at all, but I don’t believe it will be excessive.

    I still see SGEN as IMGN’s closest competitor and comparing the two companies I cannot see a reason why IMGN’s market cap should be less than an eight of that of SGEN. I believe IMGN greatly under valued while SGEN is probably about where it ought to be. Historically SGEN has often had a market cap that was less than double that of IMGN, though recently IMGN’s been less, but looking at the approvals, partnerships, pipelines and technology I simply cannot see how the SGEN market cap should be 8 times that of IMGN.

  55. IMGN: Going over the conference again, Morris gave some somewhat confusingly inconsistent reponses to questions. From what I gathered, in the n=46 expanded cohort, the subgroup of medium/high subgroup of folate receptor expressors that achieved ORR is now a little under 30% due to a lot of the expanded cohort having many prior lines of therapy. He later that the smaller subgroup of medium/high expressors who had fewer lines of therapies that achieved ORR is “meaningfully above 30%” and that they were going to target that subgroup vs an earlier line of therapy with a more robust PFS endpoint. The lack of new safety signals is a relief.

    However, he answered another question in the following way:

    Q: Okay, and then the number – you referenced the slightly lower than 30% response rate, where are we supposed to compare that with in your prior guidance, is it the 35% overall response rate in the 20 patients that were overall levels of expression of the folate receptor low, medium, or high. Is that what would be appropriate comparison?
    A: Yes.

    I’m going to trust the words he initially said, namely the initial medium/high group in the expanded cohort dipped below 30%, but we’ll know for sure when the ASCO abstracts come out. That’s still not too bad for this population, it’s a similar response rate to what the ADC IMMU132 achieved in salvage therapy TNBC which the FDA granted an SPA of a PFS end point vs investigator’s choice for a P3 trial. That said, IMMU is probably more undervalued than IMGN at this time, and I like the lead compound and indication of both companies.

  56. Wildbiftek (IMGN) – Thanks for the summary. Tying all the comments together it looks like the drug has a 25% ORR in med/high FR+ and when they exclude 5th line and beyond they go back to 40-50%. Overall quite disappointing but I understand their decision to go to earlier lines and do a full blown P3. Sounds like they are seeing a PFS of 6+ months but this is still preliminary and also hard to interpret without a control arm.

    Ville (IMGN) – Agree, disappointing news. The only thing that could surprise at ASCO is durability of response.

    Richard Baker (BLCM) – I still like the stock a lot and think it’s attractive but as you know I prefer to have limited exposure as I expect the bio-correction to continue due to broad sector issues (pricing pressure, biosimilars, elections etc.).

    Gary Mohilner (IMGN) – There’s always the question of when a study is mature enough to be considered reliable. Going to a full blown P3 vs an active control arm with PFS as 1ry endpont might work but risk is definitely higher.

    Ohad

  57. Ohad

    You had spoke previously regarding Aduro and your anticipation of negative results regarding its pancreatic vaccine, while seeming to like its future success of its LADD platform. Is it your feeling that its soon to be released phase 2b data may present a buying opportunity if stock sells off due to the somewhat expected negative data in a very hard to treat indication.

  58. HI Ohad

    Any thoughts on PETX ? Would seem to be fairly immune to insurance
    issues as people have no problem paying out of pocket for their pets.
    TIA

    Gene Mc

  59. Hi Ohad,
    You’ve suggested cabo could be a $1b drug (Current global market for 2nd+ RCC is $1.2B and this is achieved with mediocre drugs (no OS benefit) with suboptimal market penetration and (3-4 months of therapy)). What do you expect 2016 US sales (8 months) to be for RCC? Any chance it could hit $160 in 2016 for RCC, add another $40 for MTC -totaling $200 in revenue this year? Where do you see the stock price to be by December 2016? Thanks.

  60. Interesting TRVN volume up, price down on day of news of FDA meeting.

    Any surprises, good or bad?

    Would you be adding here?

  61. Hello Ohad
    Any thoughts on selling IMGN ?
    would appreciate a brief summary of the state of the portfolio companies (or some of them ) and what is expected for the near future
    Thanks a lot

  62. Hi Ohad. We discussed EDIT sometime ago, and agree it is overvalued (was at $45 little after IPO, when they filled at $16)
    On thursday competitor NTLA (Intellia) is IPO debut at $16. Do you have any opinion on Intellia? Both have early pipelines as it is a new technology but I am aware that the key issues is the IP of CRISPR/Cas9 from Doudna/Zhang labs
    Intellia signed recently a deal with REGN in some liver targets.
    I would like to get your view. Watching from the sidelines for now.

  63. IMGN: I’m personally holding until I see the data. I’d be interested to see just how much worse the data is and if they can hit this PFS endpoint on med/high expressors with <= 3 prior therapies. This sudden change of plans based on a decline in outcome does seem like a new recent low point for the company, but that seems to have been the point of keeping their options open with this trial.

    I don't think the drug is worthless or unapprovable by any means and that there's no new safety issues bodes well as this seemed to be a major issue for their ADCs like 901 and 289 in the past. It seems like a riskier situation than before, and I may also wait for FDA feedback on end point before making a move. Their partnered pipeline and general partner interest still looks quite strong as well.

  64. Seems like adding more to EXEL would be a pretty safe bet at these levels, especially now seeing OS data and the 0.66 hazard ratio. With a new M&A period starting, EXEL looks prime for the taking.

  65. $EXEL Sales guy said NCCN had 100 physicians prescribing which grew to 300 after ESMO, and now there is a six fold increase. So if we were to guess they are servicing at the minimum 1800 physicians, and if they had one patient each that was kept on this medicine Exelixis can make $97.2 million revenue for RCC in Q2, add some more revenue for MTC it comes down to approximately $100 million Q2 revenue which can double to $200 million in Q3 potentially. Initial subscribers before the label was released were most likely 3rd line and 4th line patients as the commercialization VP alluded to, and the recent increase of six fold is most likely related to 2nd line usage. They are also getting 7.4 months usage in 3rd line and 4th line patients which is pretty good. Can you listen to the earnings call and give your take on it ?

  66. $EXEL My estimates are based on each physician servicing 1 patient only, if they are servicing more than 1 which is most likely the case, the revenues could easily hit $400 million if they just had 4 patients each to service in Q2.

  67. $EXEL They might be going for a buy out with proven sales data and that is why they are not signing a Japan deal yet. More Cobi data, more Cabo data, and more sales data, and then sell the company. Does that sound like a reasonable plot ? I mean if you can hit sales that grow to a billion, and have additional indications potentially lined up, stock price goes up, pay off your debt, and sell the company. Is this a good or bad hypothesis ?

  68. Curiousgeorge: tablets started selling only last week; no indication that capsules 120mg were being prescribed off label. Worldwide 2nd line sales are 800-1.2b, so how do you figure $400 in US (especially if 2nd line is split with nivo, then competing with evro and axitinib)?

  69. $EXEL Steve, i based the approximation on listening to the conference call wherein they said they had six times more physician calls after approval indicating solid uptake. 6 times 300 is 1800 physicians calling them to prescribe cabozantinib. If each physician is on the average prescribing 4 patients with cabozantinib, and you multiply that with $13500 it comes to $400 million, the duration of therapy is also going to be longer at 7.4 months.

  70. $EXEL Some more information from the call,
    200 carton 33 percent increase with no advertisement
    300 prescribers prescribing with no advertisement
    400 cartons for RCC sold in Q1 with no advertisement
    There are 17000 RCC patients in the USA.

  71. Dave (ADRO) – Hope I’m wrong but I still think P2b panc cancer trial will fail. Not a big fan of cancer vaccines so I don’t think the platform is that valuable, the STING activator looks good,though.

    gene (PETX) – Sorry, don’t know the field at all.

    Steve (EXEL) – Launches are always hard to predict but $160M sounds too high for RCC sales the first 8 months. My guess is more towards ~$75M. The way I see it, the stock could be around $10 if launch is strong and the company starts to repay its debt (in cash and/or stock). Positive results in the CABOSUN study (1st line vs. Sutent) could help as well.

    Dan S.(TRVN) – I still like their post-operative pain program and think valuation is attractive. I personally plan to add later in the year.

    Alex (IMGN) – I plan to decide after ASCO.

    lgonber (EDIT/NTLA) – Looks like both companies have tremendous potential but I also plan to wait on the sidelines given valuation and premature pipelines.

    Wildbiftek (IMGN) – I agree, the drug became less attractive but not worthless. To me the meaningful part would be response duration/ PFS. This is crucial for understanding the potential in 4th line ovarian cancer vs. SOC.

    jh (EXEL) – I am very bullish on cabo in RCC but I don’t think a buyout is likely in the near future as companies had this opportunity before the Ipsen deal (with the exception of Pfizer, perhaps). Potential acquirers will probably want to see sales trajectory before committing serious $$$.

    curiousgeorge /steve (EXEL) – From what I understand the 6-fold increase in RCC prescription (total of 300+ to date). Hard to see Q2 sales of more than $10M… (practically 2 months). RCC has a 17k incidence in the US but not all receive 2nd/3rd line treatment and some are not clear-cell, which leaves EXEL with ~10k eligible patients. Assuming an average cost of 70k per patient, the opportunity is $700M and penetration is never close to 100%…

    Christian (CNAT) – It’s nice to see the positive trend persists for an additional 3 months but data set is still quite small, retrospective and tricky to analyze.

    Ohad

  72. Ohad,
    How does this impact HCC for cabo: Bayer’s oral multi-kinase inhibitor regorafenib has hit survival targets in a Phase III trial involving patients with liver cancer? With Sanofi, Pfizer, Amgen, AZ, Novartis all looking at MDVN, wouldn’t one of these companies take a serious look at EXEL this year?

  73. Steve (EXEL) – I think it’s more positive than negative because although it adds a potential competitor, rego is also a broad spectrum VEGFR inhibitor and cabo could be differentiated because it inhibits MET. As I wrote, EXEL could become an acquisition target but only after it demonstrates it can sell cabo in the US.

    Ohad

  74. $EXEL From Q4 transcript:
    As a reminder, the current market for second and later line RCC includes about 17,000 patients in the U.S. and approximately 37,000 patients worldwide, the global revenues for current second line RCC agents of approximately $1 billion in 2014.

    This figures are most likely all based on clear cell since they are talking about their market, and Exelixis tends to be conservative so they won’t hype the numbers up. I think a penetration of 25% 4250 patients that amounts to a $57M gross revenue per month easily a $400 million per year opportunity even with just a 25 percent penetration. If they can get additional usage in 1st line, then the pie grows even bigger.

  75. Easier said than done! “even if it were to garner around 10% market share in the space, Cabometyx could still deliver around $300 million in annual revenue within five years”. Let’s hope the sales force knock this out of the park in the FIRST year!

  76. $EXEL Ethics committees will have a hard time justifying spending 29K on Opdivo with a lower HR of .73 versus a drug that costs 13500(Cabozantinib) and has a lower HR of .66. Cabo will eat into Opdivo’s market share. Insurance agencies will also prefer a drug that has a lower cost and a higher percentage to reduce the rate of death. It just makes sense. On top of that it gets progression control, who wants to take a drug that does not stop the cancer from progressing to other parts of the body and costs more money, and has a lower chance of reducing death. If someone has knowledge about Opdivo’s sales in RCC it would be good to know so you can see how fast Cabo can eat into their market share. They have been around for six months in RCC.

  77. $EXEL What are your thoughts about potential approval of lenvatinib/afinitor on cabo market share in RCC? Will impressive OS and PFS overcome drawbacks of the need for the combination?

    $CLDX Also would be interested in commentary on which co-stimulatory agents/companies (CD27, CD40, OX40, anti-IDO1,etc.) might be most efficacious and first to market in combination with anti-PD1/PDL1 drugs

  78. “I think a penetration of 25% 4250 patients that amounts to a $57M gross revenue per month easily a $400 million per year opportunity”
    EXEL will need a little better than 25%, the early results suggest time on therapy of 7.4 months, so 4250 patients at an average of $10K per month (only 43% will pay full price) would put them around $315M. But the point is made, EXEL will not have to have 100% of the available 2nd line market, just a good percentage of 2nd, 3rd, and 4th. At the current cost structure ($240-270M annual expense), revenues of $500M would mean $.75- .85 EPS fully diluted. On a growth multiple of say 20, values the business at $15-17 PPS. Not unrealistic at all. Plus they could pay off the convertibles before 2019. Sound realistic?

  79. EXEL: good discussion. PE multiple of 20 is only given if there is growth beyond the $500m and without HCC or other prospects a more reasonable multiple would be 10 at best, $7-8 share price. Cabo will most likely get the lions share of 3L & 4L. Even if opdivo gets majority of 2L, the 75% who don’t respond after 8-12 weeks will move onto cabo. Ohad what percentage of the 17k 2L patients will eventually get cabo? If 50%, then it’s a $1b opportunity! 4-5 x sales = $4-5b valuation, $16-20 share price?

  80. Hi Ohad,

    Was wondering about you thoughts on RXDX at these levels (after recent financing) and latest trial results?

    thanks
    Steve

  81. curiousgeorge (EXEL) – I think 5k patients in the US is definitely attainable and this translates to $300M assuming 60k per patient (assuming some discounts). Superiority over Sutent in CABOSUN could definitely help to grow market share if PD-1 abs move to 1st line.
    Don’t think there are any ethical issues with choosing nivo over cabo, it all comes down to physician/patient preferences and eventually most patients should receive both.

    Gray –
    Re: lenvatinib, I don’t expect it to get approval in the US without a P3 trial.

    Re co-stimulatory checkpoints, I wish I had the answer there. I still like OX40 even though the lack of responses with Roche’s antibody is disappointing. CD27 has activity as monotherapy so there’s reason for cautious optimism imo. Not a big believer in IDO but the industry is obviously very excited.

    AMC (EXEL) – I agree with the notion that every RCC patient should be treated with cabo (and nivo) given the clear survival benefit. ex-US sales and MTC could provide an additional source of revenues and HCC + cobi are pure upside.

    Steve (EXEL) – I wish I had the answer to that… I think 5k patients is very achieveable and 10k patients represent an optimal scenario but that doesn’t get them to $1B (need HCC or other indications).

    RXDX – I have to admit I am positively surprised by their efficacy in TRK+ tumors and price has come down significantly. I was sure LOXO101 will be more active in this subgroup but so far both agents look really good. I still prefer LOXO over RXDX based on piepline and selectivity profile.

    Ohad

  82. ARGS: do you have any thoughts on the AGS-003 immunotherapy RCC phase 3 trial? Is Argos worth investing in?

  83. LIFE trading below where their CEO and CFO entry level now….. any trial coming in 2nd half of 2016?

  84. OHAD…..DO YOU HAVE AN OPINION ON A NETHERLANDS BASED BIOTECH BY THE NAME OF MERUS THERAPEUTICS ? WILL BE GOING PUBLIC THE WEEK OF MAY 15th.

  85. Evan (ARGS) – Not optimistic about cancer vaccines.

    Kenny (LIFE) – I really like the science there and preliminary clinical data are encouraging. They should have an update on FSHD and new data on LGMD in Q4. I plan on getting in later this year.

    Bouschka (Merus) – They clearly have a prolific and broad platform for bispecific antibodies. Problem is that they don’t have a lot of clinical data in hand so might be a little bit early.

    Ohad

  86. Hi Ohad,

    This may have been in a prior post when you started this whole blog/portfolio, but as I am a relatively new reader here I was curious why you don’t like to use aggressive growth large caps in your portfolio (such as VRTX, ALXN, REGN). Is it because they will have muted returns and the clinical stage companies have greater upside? You’ve picked them really well, but I always found clinical stage much harder to pick winners in than large caps.

    Thanks and great blog.
    Al

  87. Ohad,

    You mentioned biosimilar as one of the reasons to make the entire sector bearish. What do you think CHRS? It develops some biosimilar drugs in late phase and just hired Jim Delay on board.

    Thanks,
    Cloud

  88. Al – Thanks. I have nothing against bigger companies, it’s just that my focus is on Smid caps.

    Cloud (CHRS) – Not sure how I feel about their refocused pipeline and de-prioritization of the TNF programs and Neulasta. To me, their decision shows that the biosimilar market is going to be much more competitive that people originally thought and this will have a significant impact on price erosion.

    Ohad

  89. TRVN very weak lately. I assume its based on expectations of failure in AHF. Any other reasons?

  90. Hi Ohad,

    any thoughts why MRNS is so oversold? Looks attractive at these levels (R/R)

    n0cturne

  91. EXEL: 2L pie seems to be getting smaller with more competition. Ohad, are there any P2 studies being conducted for cabo (eg first line combo, 2L combo) that FDA could approve without P3? CABOSUN trial? If so this would be HUGE for EXEL!

  92. Steve- Lenv/Ever combo was voted down by NCCN for insufficient data. Despite the FDA’s surprising approval, I wonder how many onco docs will adopt this expensive and toxic option when the KOL’s weren’t comfortable with the data? May not be much of a threat to Cabo’s place in the treatment landscape. Think about the amount of data they were looking at….50 patients. And wasn’t it only approved based on PFS, not OS?

  93. Ohad
    ASCO abstracts will be published 05/18. Anything you will be looking in particular?

  94. PaulB (TRVN) – I suppose some of the weakness can be attributed to the AHF data. I personally plan on buying more if results are negative and the stock drops.

    n0cturne (MRNS) – There is obviously a lot of nervousness going into P3 readout and the fragile X data, both are high risk events. I still feel risk/reward is good given the optionality in SE and SAGE’s indications.

    steve (EXEL) – Very surprising, I was almost certain they won’t get approval. I still think cabo is a much better drug, with a similar HR vs. Afinitor to what Lenvima+Afinitor achieve (in a P2…). Interesting question regarding approvability of CABOSUN… Regardless, I still think cabo will become a dominant RCC drug with $350M in sales under conservative assumptions.

    AMC (EXEL) – Completely agree, data package for lenvatinib is less compelling than that of cabo. I am having a hard time understanding the FDA’s decision…

    Ohad

  95. Andre – Doesn’t look like an exciting meeting this year. I am very curious to see Rova-T’s data given what ABBV paid for it.

    Ohad

  96. OS Cabo 21.4 months vs evero 16.5 months = +30% (phase 3)
    OS Opdivo 25 months vs evero 19.5 months = +28% (phase 3)
    OS Lenvatinib 19.1 months vs evero 15.4 months = +24% (phase 2)
    OS Lenvatinib + evero 25.5 months vs evero 15.4 months = +65% (phase 2) HR, 0.67

    Granted the L+E combo has high toxicity, the obvious question now is how well will the cabo+sunitinib combo or future cabo+nivo or cabo+evero or nivo+ipi combos fair?
    Great for patients as companies compete to figure out the best treatment course.

  97. Ernie/ Ohad,
    It’s interesting that the posted OS HR for L+E, 0.67, was worse than Cabo’s Phase 3 trial OS HR of 0.66. Looking at Ernie’s data set here, it’s confusing as to why that would be?

  98. Hi Ohad,

    What are your thoughts on the upcoming STORM interim? The P1 done with a similar drug regimen ie selinexor(80mg)+dex(20mg) produced an ORR of 67%. This population had median 7 prior therapies. Since the STORM population aren’t required to have 7 prior TX the threshold mentioned recently of > 20% ORR should be achieved very easily. The only wildcard could be Darzalex resistant patients who were not treated in the P1 trial. However there are unlikely to be too many of those.

    I also find it noteworthy that the next gen sin drug is being initially tested in refractory MM indicating mgmt seems more confident in this indication than any other.

    thanks

    Rick

  99. Ohad
    TRV027 failed to meet either the primary or secondary endpoints in the Phase 2b BLAST-AHF study in acute heart failure (AHF)

    It looks that they will open below 5.50. Do you plan to add and at what level?

  100. Hi Ohad,

    Any thoughts on Aduro after their PII failure?
    They have a low EV and now the company is more focused around STING.

  101. Ernie/AMC (EXEL) – Hazard ratio provide a better sense for the clinical benefit because they capture the difference not only at the medians. Lenvatinib’s data is clearly positive but overall cabo’s package is more compelling imo from various aspects (P3 vs. a 100pt P2, a single drug vs. 2 drugs, less toxicity, lower cost etc.).

    Rick (KPTI) – I am still undecided there. Initial data with dex was really impressive but we’ve seen so many cases in which a promising efficacy signal wasn’t corroborated by a larger study. I like the new XPO1 molecule because it doesn’t penetrate the brain and could provide a better therapeutic window.

    biogirl/andre (TRVN) – It doesn’t change my opinion on the company, primary asset has always the post-op pain program. Yes, I plan on adding more TRVN at these levels.

    Emmanuel (ADRO) – STING program is interesting but early (just started P1) so I prefer to wait.

    Ohad

  102. See you are still positive on EXEL, do you think it is OK to get in EXEL at this level ? Thankyou.

  103. Ohad
    Why SGEN is up big on a day when PD-1 is approved for HL?
    Opdivo label is 2-nd line after adcetris, but still a future competition.

  104. Ohad
    It looks that CELG does not like AG-120 anymore. But they will keep stake in AG-221 I thought that if IDH2+ works, IDH1+ should work as well. Moreover IDH1+ should have at least 5 times more cases.
    Very strange move, unless CELG knows that 120 is going to fail ?!?

  105. ruhu (EXEL) – Yes I am still positive on EXEL because I think cabo is the most effective RCC drug out there.

    andre (SGEN) – Investors were relieved to learn that PD-1 will be reserved to post Adcetris settings and BMS will probably have to run P3 to get approval in earlier lines.

    Re AGIO/CELG – It definitely doesn’t project positively on AG-120, perhaps CELG’s decision is related to disappointing activity in solid tumors. Looking at the bright side, new deal terms are quite compelling ($200M upfront for early stage stuff).

    Ohad

  106. Hi Ohad,

    Immunogen updated their MS (IMGN853) data from their expansion on their website. Total population ORR fell to 26%.

    For n=16 medium/high expressors w/ <= 3 prior therapies, ORR was 44% with PFS of 6.7 months.

    For the complement of this n=30 (where 9 were low expressors and 21 were medium/high but with 4 to 5 prior treatments) ORR was 17% (n~8) with PFS 4.2 months.

    From their ASCO abstract released today (which was probably at an earlier cutoff as they include unconfirmed responses in their numbers):

    "To date, objective tumor responses were observed in 19 pts for an overall response rate (ORR; confirmed and unconfirmed partial response [PR] or complete response [CR]) of 40%."

    "… 33% (3/9) low (25-49% of cells with ≥ moderate expression), 33% (5/15) medium (50-74% of cells with ≥ moderate expression), and 48% (11/23) high ( ≥ 75% of cells with ≥ moderate expression) expressers."

    So about 11 patients out of the 19 with substantial regressions at first checkup relapsed. Presumably many med/high expressors with 4-5 lines of therapy weren't able to make it to the follow up with the same regressions.

    Their benchmark was:

    "Current single-agent therapies for platinum-resistant ovarian cancer typically have an ORR of 15-20% and median PFS of 3-4 months, including in patients receiving no more than two prior regimens.1"

    Safety seems promising. From their press release:

    "Mirvetuximab soravtansine was generally well tolerated, with most side effects Grade 1 or 2 (least severe grades). Of particular note, incidence of blurred vision was reduced from 55%, mostly Grade 2, in the first 20 patients enrolled to 39%, mostly Grade 1, among the 26 patients added with the expansion of the cohort. Other side effects reported in more than 20% of patients were diarrhea, fatigue, nausea, vomiting, peripheral neuropathy, increased AST, keratopathy, and abdominal pain."

    From their abstract:

    "The most frequent grade 3-4 drug related AEs were fatigue and hypotension (2 patients each – 4.2%). Four pts discontinued for AEs. Thirteen pts remain on IMGN853. The median duration of follow-up is 4.2 months."

    Any thoughts?

  107. EXEL ASCO data looked better than expected, comparison with prior nivo suggests cabo could dominate second line and the possible combo with anti PD-1/PDL1 might be the next big thing.

    I see roche taking this out.

  108. ARRY
    Curious on your take of binemetinib post immunotherapy data for nras and ecorafenib’s potential for braf colorectal in combo with cetuximab

  109. $EXEL Cobimetinib is effective in Erdheim Chester rare disease. Do you know the patient population ? What do you think of the Cobi/Cabo data in ASCO ? Cabo is acting as an immunomodulator in TNBC according to one other abstract.

  110. Wildbiftek (IMGN) – I still don’t understand why they are not going after FR-high for accelerated approval. According to the abstract they have 48% unconfirmed response rate. Even if the confirmed response rate is 30%, in this population an accelerated approval is plausible.

    JH (EXEL) – Don’t forget Roche is pushing atezo+Avastin for RCC. Cabo’s data are good, didn’t see anything important that we didn’t already know.

    anthony (ARRY) – Very intrigued by the post PD-1 activity, waiting to see OS data.

    curiousgeorge (EXEL) – There are preliminary good signs about MEK inhibitors in combo or post PD1 from ARRY and EXEL. Still early but v interesting. Not familiar with Erdheim Chester, will take a look.

    Ohad

  111. Hi Ohad,

    I believe the overall response rates of expression stratified groups sampled by immunogen by trial progress went like this:

    Nov 2015:

    High – 9/10
    Med – 1/6
    Low – 0/6

    Feb 2016 ASCO abstract deadline, first expansion data and data from 2016 abstract (includes unconfirmed responses):

    High – 11/23
    Med – 5/15
    Low – 3/9

    May 2016 Q3 CC and 5/18/2016 announcement; confirmed total sample n = 46 ORR is now 26% or 12 patients across the three groups and the estimate below are based on press release breakdown for investors (upper bound based on Feb data above):

    High – ~7/23 (<= 11 out of 23 from Feb)
    Med – ~3/14 (<= 5 out of 14 from Feb)
    Low – ~2/9 (<=3 out of 9 from Feb)

    Reasoning for May estimate: Morris had said on the CC: "In the more recent data, we have now seen confirmed responses in patients with medium expression, and even in a couple of patients with low expression." So I'm assuming around ~2 patients in the low group w/ confirmed ORR which means that most of the losses from the 19 patients who had confirmed / unconfirmed responses in Feb were in the med/high group. That leaves 10 in the medium and high groups; to tease something out for the medium and high groups, the percentage of conf/unconf responses from med and high groups respectively were 36% and 48% so about a 4/3 times greater rate for high; solve for 4/3 * (ORR rate of med) * 23 + (ORR rate of med) * 14 = 10 and this implies that out of 10 we should see roughly 3 and 7 confirmed responses in med high.

    (The breakdown of the data they put in their press release was :
    Proposed P3 group – For n=16 medium/high expressors w/ <= 3 prior therapies, ORR was 44% (n=7) with PFS of 6.7 months.

    Complement of group – For the complement of this n=30 (where 9 were low expressors and 21 were medium/high but with 4 to 5 prior treatments) ORR was 17% (n=5) with PFS 4.2 months.)

    So even in the high group there was a substantial drop in response rate from November to this year; it may be that the 7/23 (< 30%) confirmed ORR rate is too low for them to have a comfortable meeting w/ the FDA so they decided to change the endpoint for the trial. He also said in the CC: "We do have more heavily pretreated patients in the population that we've seen since ASCO." If there is a good correlation, it would be prudent to exclude more advanced patients if they have good evidence that the number of pre-treatments affected results. I recall that positive results in P2 for Farletuzumab and Vintafolide also came from less heavily pre-treated patients.

    What are your thoughts about the chances of success for their proposed P3? I'm neutral on the stock, and I think I will hold. I'd like to see how the FDA reacts; I think the better safety data means they'll likely sign off on the trial but I'm looking for whether they can secure BTD. By comparison, IMMU is getting plenty of attention for their ADC for their slightly under 30% confirmed ORR in TNBC in an unenriched population. There's also plenty of combo data to come soon as well so all those things could be short term catalysts.

  112. P.S. I meant to say that in the high group, a result of 7/23 ~ 30% (not < 30% my bad) estimated from the Feb numbers w/ might be too low for a successful meeting w/ the FDA for an ORR endpoint. IMMU had around 30% ORR and secured an SPA for a P3 w/ a PFS end point in heavily pretreated TNBC.

  113. ARRY
    Thanks for the reply. Do u find it concerning that the interim OS HR is 0.81? I am not a statistician, but I don’t think that is statistically significant. I recall from your reply to other posters that given limited options of NRAS, binimetinib will likely be approved based on PFS. Do you still think that is the case?

  114. Ohad

    Any comment on the Stemline abstract for ST-401?
    http://abstract.asco.org/176/AbstView_176_168280.html

    Seems encouraging to me with some patients being bridged to bone marrow transplant and high ORR. Duration I guess is the question.
    Do you think this P2 is enough to get approval if they can show sustained response and bridging enough pts to BM transplant
    would you add more?
    thanks

  115. Ohad
    Do you have an opinion about DNAI.
    On June 6 they will report Ph 2 data for BCL2 target in pts with relapsed or refractory DLBCL.

  116. EXEL cabosun reached endpoint for PFS. Seems like this study might be enough for approval if secondary points are reached based on recently approved everlourimis study.

  117. Hi Ohad;

    Do you think biotech correction will continue or this run up just for per-ASCO, then we will have another sell-off.

    Thank you,

  118. Ohad, EXEL – why can’t first line approval be granted on the CABOSUN trial? What are your revised sales estimates for 2016-2017? 4000 patients seems very likely, $10k avg, $480m full year? If we include $38 MTC, $25m EU, cotellic….$500m seems likely?

  119. Hello Ohad
    if you have to recomend 3 stocks to buy now, what would they be?
    EXEL,TRVN,LIFE ?
    EUSA Pharma payed $2.5 million for tivo , is there any chance to europien aprovel?
    Thanks

  120. EXEL-If FDA agrees to first line label expansion on CABOSUN then this presents a billion dollar opportunity. EXEL would be on par with onyx or MDVN. Ohad, is EXEL derisked completely?

  121. Hey Ohad
    nice to see excel continue to deliver… it’s been a long journey back….
    I wanted to ask you again about HTBX… the company has valuation of under $10M, and two phase 2 readouts later this year… also, what is your take on the recent Adam Feuerstein tweet about some companies having very lofty valuations versus others being under water (he was comparing ZIOP to ONCS), but it seems this quite common… you take all the CAR-T companies, which have lofty valuations… and then look at HTBX, with has an off-the-shelf therapeutic that can target multiple antigens and provoke t-cell responses over the long-term (sure, some of these things have to be verified…) what is your take? Thanks a lot
    Dan

  122. Hey Again
    regarding XENE, why wouldn’t they partner with a CRISPR company to target some of the genetic discoveries they are making…. for instance regarding Nav1.1 and epilepsy which they say is caused by this one gene mutation… would’t that be a better way to go about it, than develop an inhibiting drug?
    Thanks
    Dan

  123. Ohad

    You haven’t spoke regarding ESPR in some time and the stock has traded sideways for the last several months. What is the next major data point for the company and what are your feelings regarding eventual approval for their compound.

  124. Ohad,
    Also in regard to ESPR discuss the CETP inhibitor evacetrapib failure in CVOT despite lowering LDL. Will this impact ESPR ands its chance to succeed in CVOT.
    It seems without an overall win in CVOT…which now has an even higher bar setting, that this may be only an agent serves the limited niche of station intolerant patients. If true, is that end result baked in to the current valuation.
    Frank

  125. Hey Ohad
    hope things are well. Are you attending ASCO?
    regarding the NASH space, are you following some of teh companies there, besides Conatus? What is your view on GLMD?
    Thanks
    Dan

  126. CPXX…What a monster! that should be in your list of catalysts in 2016! From $1 to $30 in a few months! (JAZZ offer to BO) If that does not improves sentiment of BIOS, I don’t know what else!

  127. Hi Ohad,

    I am a long time EXEL shareholder and wanted to share a few recent, encouraging observations:

    1. Baker Brothers now own 2.6mil plus direct shares acquired between 12/31/15 and 03/31/16. In addition, they also purchased a substantial portion of the 4.25% debt EXEL issued back in 2012 and have the rights to 20 mil shares (if the debt were exchanged vs. retired in cash).

    This debt was purchased by Baker Bros between 06/30/15 and 09/30/15, right around the time the positive PFS data was announced for METEOR. Link – http://www.sec.gov/Archives/edgar/data/1263508/000114420416102596/0001144204-16-102596.txt

    2. Obviously good news released about CABOSUN which even if they are insufficient to file an sNDA for 1st line RCC will undoubtly add some incremental sales for off-label 1st line scripts (assuming NCCN guidelines revised).

    3. Cobi/Atezo (REALLY EXCITING) – The oral presentation related to Phase I mCRC results look very promising as it could represent the first drug combo to work in mismatch proficient mCRC (which is approx. 85% of the 57K new cases diagnosed in US each year).

    If the drug combo were approved in this indication, it could become the gold standard and could be MAJOR to EXEL’s bottomline (85% x 57K patients = 48,450 eligible patients x 40% market penetration (low?) = 19,380 treatable patients x $5,000 per month ($5K is assuming Roche greatly lowballs the value of Cobi vs. Atezo in the combo) = $97mil in EXEL monthly revenue x 7 months on therapy = $678mil in annual revenue potential! This is HUGE (if happens) and could actually make Cobi more valuable than Cabo.

    What I find very interesting and encouraging about this occurring (Phase III for Cobi/Atezo in mCRC) is that Genetech posted a job last month for a Clinical Scientist Associate for the Cobimetinib Program.

    Per the job listing, one of the duties is to design new PHASE III trials for Cobi! Maybe I’m reading too much into this, but I think it will be for a Phase III mCRC trial which will likely be initiated shortly (link to job posting https://www.linkedin.com/jobs/view/129752146)

    Thanks and congrats on being an EXEL shareholder, I really believe we see double digits this year (finally).

  128. Sorry for the late reply, just finished a hectic period with limited connectivity.

    Wildbiftek (IMGN) – Thanks for providing this analysis.I think the proposed P3 is a viable registration route but I still wonder whether IMGN could have pursued FR-high pts with a smaller/shorter study. Of course, IMGN has much more information than I do, will have to wait and see next week.

    Anthony (ARRY) – 0.81 is not very compelling (the abstract didn’t have additional info) but this was from a n early analysis so the more important figure will be given at the conference (224 events which is >50% of patients). Yes I still think binimetinib is approvable based on PFS (and hopefully even an OS trend).

    roland (STML) – Agree about durability info crucial for understanding the true potential of the drug in BPDCN. Given the rarity of this tumor I think a small single arm P2 should be enough for approval.

    andre (DNAI) – Yes I am eagerly waiting to see their data and see if they maintained the impressive ORR in DLBCL. My concerns with this program is more conceptual, i.e how is it different from small molecule BCL2 inhibitors which did not demonstrate great efficacy in DLBCL from what I recall. Market cap is very low so risk isn’t huge imo.

    jh (EXEL) – Cabo continues to deliver against a very hard competitor (don’t think any drug has ever beaten Sutent in 1st line RCC. With the recent approval of lenvatinib as a precedent an approval is possible but it’s important to remember CABOSUN recruited only int/high risk patients so this may be reflected in the label.

    steve – Very hard to predict these things. Expectations going into ASCO are already tempered so I don’t expect a post-ASCO sell off. I do expect pricing challenges (eg NICE’s decision regarding Opdivo in lung cancer) to persist during 2016, which should put pressure on the sector but could be good news for Smid caps.

    Re EXEL , hard to predict 1st year sales but I don’t think they can surpass $100M in the US in 2017.

    Alex – I never recommend to buy or sell specific stocks as every investor has a different profile. Personally I am long EXEL and TRVN and believe both stocks are attractive. LIFE falls under a different very high risk profile, science is great but clinical data is still very limited.

    Bob (EXEL) – No stock is de-risked completely but with the data package cabo has in RCC this is as de-risked as it gets (prior to commercial sales). Yes, 1st line approval should get the drug to $1B globally.

    Ohad

  129. Hi Ohad,

    Re EXEL, at current prices the marketcap is around 2.4B using a fully diluted share count and EV is around the same. At what point do you think risks would outweigh further rewards? It seems competition is heating up in the RCC market and EXEL cash burn is quite high. IS it still worth buying or would you see how sales are farinf 1st?

    Regards

    Rick

  130. Have you ever looked at LION? Recent management changes seem all for the better. Company raised $100 million today.

  131. Dan
    HTBX – I don’t follow them closely but I am not a big fan of their technology.
    XENE – It depends on the target. For some targets (like ion channels) small molecules can be developed but there may be targets for which genetic manipulation like gene editing is required. Gene editing is very exciting but it’s still early days and the technology is not proven in humans.

    Alex – Tivo and cabo both target RCC. Tivo’s P3 was in 1st line patients and cabo’s P3 was in 2md/3rd line patients.

    Richard (PRTO) – Sorry, don’t know them.

    Dave (ESPR) – Next readout is P2 in combo with high-dose statins, which is quite important given the concerns around this setting and the fact the ETC1002 works upstream of statins. I am still optimistic about the drug and believe it could become a 1-2B drug based on LDL and CRP reductions observed to date. As the case with PCSK9 antibodies, ESPR might get approval without outcomes data but these are necessary for commercial ramp up.

    Steve (ARRY) – Will decide after ASCO, MEK inhibitors may become very attractive as PD-1 add on.

    Frank (ESPR) – I don’t think CETP inhibitors provide a good read- across as their primary activity is not LDL-C. ESPR’s drug is more similar to statins, which have been shown to significantly reduce CVOT events. Statin intolerant patients represent a huge market in itself imo.

    Dan – Not attending ASCO this year. Not familiar with the NASH space.

    lgonber (CPXX) – Agree, an AMAZING story. It certainly helps but I don’t think it will have a dramatic impact on sentiment.

    curiousgeorge (EXEL) – Thanks for sharing, good news reagrding tolerability in light of prior experience with Sutent/Votrient +PD-1. I don’t think we can conclude anything else based on these comments.

    Justin (EXEL) – Thanks for sharing these observations. Indeed looks like several things moving in the right direction. Cobi (and other MEK inhibitors) could become significant if data at ASCO look good but one has to remember EXEL’s profit share in the US goes down significantly beyond $400M in annual sales (if I recall correctly).

    n0cturne – Sorry don’t know them.

    Eric (EXEL) – I believe the case for cabo is much stronger as its data set is from a large p3 (and now CABOSUN represents another positive readout) and it is given as monotherapy (tox, cost, option to use Afinitor at a later line) so most physicians and patients should prefer it over levatinib. Whatever tolerability issues cabo has (it already has an established safety profile), other VEGFR inhibitors face a similar challenge.

    Bouschka – Thanks, all is well :)

  132. $EXEL This was posted on yahoo mb by exel_long
    From 10-Q 4-May-2016: …”on May 3, 2016, we issued a formal notice of dispute to Genentech, per the collaboration agreement’s dispute resolution procedures” … “we believe Genentech’s cost and revenue allocations for COTELLIC, as determined exclusively by Genentech, have been contrary to the applicable terms of the collaboration agreement.” …”If the dispute is not resolved within thirty days of Genentech’s receipt of this notice, we intend to initiate an arbitration
    ——————————
    Any comments on this, and what are Exelixis chances of getting a price increase for Cotellic ?

  133. EXEL will most likely be bought out. Currently 228m shares outstanding, 250m is we take the unvested shares; $287 debt converted at $5.31/share will add an additional 54m shares /dilution: totaling 302m shares outstanding. Assuming first line RCC is in play, $1b peak sales 4-5x multiple we are looking at 4-5b valuation at $16-20/share. Good luck!

  134. Alex: doubt tivozanib will be a real player. From SA:
    “…the FDA rejected its New Drug Application (NDA) for kidney cancer due to inconsistent study results.
    The company is undeterred though. It sought FDA guidance about a new 314-subject Phase 3 trial assessing tivozanib as third-line treatment in advanced RCC. The regulator responded that the data “may support” the indication. As always, it will be review issue”

  135. ARRY
    Thanks for the reply Ohad. Would like to know your opinion on the data for ecorafenib + cetuximab in BRAF CRC. The overall survival data looks very good with an n=100 compared to historical data, and ARRY has decided to do a 600 patient phase 3. Do you have an estimate of what it would cost given their partner is paying 40% of it?

  136. Ohad
    thanks for the DNAI response.
    You were concerned of the BCL2 inhibitors efficacy.
    ASCO data for Venetoclax after KI discontinuation for BCL2 target was ORR 76% and CR 7%.
    Does it increase your confidence in the DNAI data for the BCL2 target?
    DNAI drug is a DNA interference drug and probably should have better safety and tolerability profile compared to small molecule BCL2 inhibitors.
    At any rate, Merrill Lynch expects DNAI to be one of the ASCO winners. Let see on June 6.

  137. HI Ohad
    you wrote
    “I do expect pricing challenges (eg NICE’s decision regarding Opdivo in lung cancer) to persist during 2016, which should put pressure on the sector but could be good news for Smid caps.”
    how it could be good for Smid’s ?
    Thanks

  138. TRVN

    Hi Ohad,

    any near-term catalyst for TRVN in sight? Results from TRV130 will be published in the first quarter of 2017. Where do you see the stock price in Dec2016/Jan2017?

    Best Regards, n0cturne

  139. curiousgeorge (EXEL) – Thanks, very interesting especially that now Cotellic is gaining importance as a PD-L1 “potentiator” . Hard to assess the outcome of this move.

    Alex (EXEL/AVEO) – I don’t think tivo is a major threat given the recent CABOSUN data. AVEO are going after Nexavar as a control arm (again), which is considred inferior to Sutent.

    Anthony (ARRY) – I think the doublet and triplet data are good although comparing OS to historical data is very unreliable. In addition, it is unclear whether adding alpelisib is worth the toxicity and financial cost. A 600 patient trial should probably cost $30-40M.

    andre (DNAI) – I am not worried about BCL2 as a target, it is the competition with venetoclax I am worried about.

    Alex – In this type of environment te only way to grow is introducing new differentiated drugs and for this large biopharma will have to acquire small companies.

    n0cturne (TRVN) – Cannot think of dramatic catalysts this year. P3 results for oliceridine are expected in 1H:17.

    Ohad

  140. Ohad Thanks for the reply. The triplet will be binimetinib/encorafenib/cetuximab for the phase 3 not alpelisib . Phase 2 trials of dabrafenib trametinib and cetuximab in BRAF CRC shows better response rate than just dabrafenib+ cetuximab. Maybe because of the competition, ARRY wants to make sure they have a triplet group as well.

  141. Also do you see a chance that Merck or BMY will collaborate with ARRY and use binimetinib with their PD-1 inhibitors to compete with Roche and Astrazenaca? I am not sure if BMY or Merk has an in house MEK.

  142. Yes a dropoff, but 30% above $400 million is still significant. Exel actually got decent terms to offload development costs. These deals usually require royalties to offload the development costs. Exel certainly got an unfair deal on drug pricing though.

    Under the terms of the Agreement, Exelixis is entitled to an initial equal share of U.S. profits and losses for cobimetinib, which will decrease as sales increase, and will share equally in the U.S. marketing and commercialization costs. The profit share has multiple tiers: Exelixis is entitled to 50% of profits from the first $200 million of U.S. actual sales, decreasing to 30% of profits from U.S. actual sales in excess of $400 million. Exelixis is entitled to low double-digit royalties on ex-U.S. net sales. In November 2013, Exelixis exercised an option that will permit it to provide up to 25% of the total sales force for cobimetinib in the United States, if the compound is commercialized, consistent with the Agreement’s terms.

  143. EXEL phase III with roche in CRC. EXEL also challenging Roche on cobi agreement. I thought Roche might buy them as the combo could be huge in the future in many indications. But the time to do it was before the ipsen deal.

  144. hello Ohad,

    what do you think about ASCO-updates from MorphoSys on MOR202 and MOR208?

    Thanks as always!

    Christian

  145. Anthony (ARRY) – Thanks for the clarification, makes sense. Regarding MRK/BMY using bini , it makes a lot of sense as I am not aware of them having active MEK programs. They can also choose NVS’ Mekinist.

    Chris (EXEL) – Agree.

    jh (EXEL) – I also assume it’s too late for an acquisition after the Ipsen deal. Cotellic will have to become increasingly important for Roche to bid for EXEL.

    Christian (MOR) – I don’t find those data sets exciting.

    Ohad

  146. Ohad: EXEL- what if Ipsen is the ultimate acquirer? The deal as you said was “very rich”! $855m for 2L RCC; with 1L in play it is more than plausible that they would be interested? Their CEO has deep connections, raising money wouldn’t be an issue, especially is the acquistion is based on initial cash and subsequent payments based on sales and trial milestones (eg $2.5-3b upfront with $1-2b in future milestone payments). Thoughts?

  147. $EXEL The way i see it is that Exelixis waiting to see the Combination results and the Cotellic results before engaging in the next set of steps, and will file for sNDA for 1st line RCC. I think based on the twitter feeds of Sumantha Pal and Apolo there seems to be a general enthusiasm about the differentiating factor Cabo brings to the combination story because it makes the disease receptors more open to detection by the immunotherapy drugs. I might be far fetched here but i think the combination might CURE RCC. If that happens the price of Exelixis can go astronomically high. This is my far fetched guess. So Exelixis therefore i think is setting themselves up for a buyout. The price might be above $100 if all the stars line up. You should listen to the Roche presentation and the ASCO presentation of Exelixis, and you can read between the lines. I heard the word CURE.

  148. $EXEL At 100 it is a 22 billion dollar company, i know u will not agree to this valuation but it can happen if the combination results are blockbuster. Cotellic is already a block buster and the reason why Exelixis is seeking arbritration is that Roche wants to hide the value of Exelixis, they probably low balled Exelixis in a buyout offer so Exelixis did the right thing going for Ipsen.

  149. $EXEL I meant hide the value of Cotellic, well it cannot be hidden anymore.

  150. hello Ohad

    your take on the NEMO resilts would highly be appreciated

    thanks!
    Christian

  151. Hi Ohad,

    I was wondering if you plan on doing an update article on EXEL to address all the new developments (cabo RCC bone mets pfs/os, cotellic potential in CRC)

    Thanks!
    Justin

  152. Hi Ohad,

    Immunogen posted their ASCO poster of the IMGN853 data of 40 patients with EOC and 6 with a variety of other cancers:

    http://www.immunogen.com/application/files/5314/6496/7708/ASCO2016MIRVPH1AB5567.pdf

    I believe that the this poster data corresponds to the data they presented in May from the total sample confirmed ORR they report of 26%; presumably the responses on the waterfall with an asterisk progressed prior to being confirmed judging from the relatively modest median PFS figures.

    There were 22 high, 13 medium, and 8 low expressors for whom they had post-baseline measurements and plotted on their waterfall. Of confirmed responses stratified by folate expression:

    high: 6 / 22 (1 unmarked bar which I don’t count)
    medium: 4 / 13
    low: 2 /8

    Interestingly for the 4 CRs both confirmed with 1 unconfirmed:

    high: 2 (1 unconfirmed),
    medium: 1
    low: 1 (!)

    So even a low responder had a rather profound reduction in tumor size. This seems to somewhat weaken the initial thesis that higher folate receptor expression corresponds to better responses but the signal still seems to be there.

    The pre-treatment breakdown seems like an important one. By the poster 23 (50%) had 1-3 prior therapies and 23 had 4 or more. For just this stratification into more lightly pre-treated (1-3) vs more heavily pretreated (4+), confirmed ORR was

    1 to 3: 39% (9)
    4+: 13% (3)

    the latter implied from the total confirmed of 12 out of 46. This seems like a fairly important criteria, but whatever control arm they choose will likely also benefit from this as well.

    The spider plots looked promising, almost a little like an IO agent. (Perhaps an immune response is triggered?) Many didn’t paths didn’t have very long follow ups, but the ones added since 2015 look decidedly worse as they said on the conference.
    (compare the spider plots with the new paths added here to the original paths from http://www.immunogen.com/application/files/3914/5877/3807/biomarker_AACR_EORTC_Poster_final.pdf)

    There’s a bit more obfuscation since last year, but this still looks like a promising agent. Any thoughts about the poster, the responses, and the AEs?

  153. Ohad re Morphosys: a duration of response of 20months with MOR208 is not ecxiting?

  154. Ohad re Morphosys (part 2):
    Please take a look at the Morphosys investor presentation at ASCO.

    My highlights re MOR208:
    Time to response and DoR
    * Median DoR in DLBCL was 20 months
    * Median DoR was not reached in iNHL patients, with 72% of responders without disease progression at 16 months and 6 responses ongoing

    And even MOR202 now shows comparable efficiacy to daratumumab in monotherapy and in combination with iMIDs with two potential advantages:
    * far lower infusion reactions compared to daratumumab -> infusion time of 1h could be reached instead of 3-6h with daratumumab
    * there is a strong rationale that the DoR could be longer than with daratumumab because of preservation of NK Cells and because the antibody doesn’t deplete the target CD38 as biopsys showed (in contrast to daratumumab)

    So i think it’s worth for you to take a second look.

    Presentation:
    https://www.morphosys.de/sites/default/files/presentations/160606_mor_asco_investor_reception_0.pdf

    Webcast:
    https://www.webcaster4.com/Webcast/Page/1328/15470

  155. Steve (EXEL) – My guess is that potential acquirers (let alone Ipsen who already has a stake) would want to see at least 2-3 quarters of sales before acting.

    curiousgeorge (EXEL) – Combination with PD-1 in RCC as well as other indications could be an important value driver, no doubt. If MEK inhibitors are indeed PD-1 potentiators then their value will increase dramatically but the jury is still out.

    Christian/Jack (ARRY) – NEMO data are obviously disappointing. Let’s hope KRAS+ NSCLC data will look better later in the year.

    Justin (EXEL) – See my recent post about ASCO.

    Wildbiftek (IMGN) – mirv is definitely active but the lack of correlation with FRa expression is disconcerting.

    Ville (MOR) – Thanks for providing this information. Yes, that’s good durability but response rate is still rather low in DLBCL. Re: MOR202, data set was limited and hard to interpret without a control arm

    Kenny (NERV) – Sorry don’t know them well.

  156. I believe what you posted made a bunch of sense. However, what
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