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. 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!


  2. 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?


  3. 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…



  4. 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.


  5. 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?


  6. 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.




  7. 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?


  8. Hi Ohad,

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


  9. 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.



  10. 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.


  11. 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 ?!?


  12. 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).



  13. 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?


  14. 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.


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


  16. $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.


  17. 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.



  18. 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.


  19. 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.


  20. 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?


  21. Ohad

    Any comment on the Stemline abstract for ST-401?

    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?


  22. 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.


  23. 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.


  24. 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,


  25. 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?


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


  27. 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?


  28. 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


  29. 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?


  30. 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.


  31. 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.


  32. 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?


  33. 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!


  34. 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 –

    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

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


  35. 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.



  36. 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?




  37. 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 🙂


  38. $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 ?


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