Notes from ASCO 2016

Although this year’s ASCO contained a limited amount of groundbreaking data, it provided some interesting take-aways and signaled important trends in oncology drug development.  Below is my take on a quiet but important meeting.

Immuno-oncology – PD-1 combinations at their infancy

As in previous years, the meeting was dominated by PD-1/PD-L1 antibodies. Now that PD-1 blockers have been tested on every tumor known to mankind (see below a great figure from Merck), focus is shifting to combination regimens with PD-1 as a backbone. Combination partners range from other immune checkpoints to chemotherapy, targeted therapy and radiation.

Keytruda - tumor types

The most active strategy is combining PD-1 antibodies with other immuno-oncology agents (CTLA4, IDO, OX40, KIR, 41BB, LAG3, CD27 etc.). After none of these drugs was able to come close to efficacy demonstrated by PD-1, there are now tens of different combinations in clinical development (including some in P3). The only validated combo is Opdivo+Yervoy in melanoma. At the meeting, BMS (BMY) presented data for this combination in SCLC and gastric cancer but in both cases results were underwhelming and the combination appears only slightly better in SCLC (overall survival of 6-7.7 months).

Novel immuno-oncology agents (OX40, 4-1BB) – Two highly anticipated data sets involved Roche’s OX40 agonist (MOXR0916) and Pfizer’s (PFE) 4-1BB agonist (PF-05082566). Roche’s preliminary data for MOXR0916 +atezolizumab showed a good safety profile but efficacy was underwhelming with only 2 responses in 51 patients. Pfizer’s 4-1BB agonist had a more encouraging data set with a confirmed responses rate of 26% (6/23) across various tumor types (including a CR in SCLC and RCC, respectively). Interestingly, Pfizer’s antibody does not have toxicity issues seen with an earlier 4-1BB program from BMS.

41-BB

IDO was the elephant in the room – Incyte’s (INCY) IDO inhibitor (epacadostat) is in multiple open label combination trials with various PD-1 inhibitors, however, no data were reported at ASCO. IDO is still regarded as a promising target but excitement waned considerably after last year’s SITC, where epacadostat+ Keytruda demonstrated lower than expected efficacy. Incyte and Merck recently advanced the combination to P3 in melanoma.

Roche is evaluating its IDO inhibitor (GDC-0919, licensed from Newlink Genetics [NLNK]) with atezolizumab in a trial that started in July 2015.

Chemo combinations – Chemotherapy combinations continued to demonstrate intriguing but preliminary efficacy, especially in 1st line NSCLC.  For some combinations, response rates were higher than historical data but results were hard to interpret without a control arm, especially in light of inconclusive PFS figures. The role of PD-1+chemo in lung cancer will become clearer next year as multiple P3 trials exploring this approach are expected to read out. Later in 2016, Merck will have an interesting readout from a P3 evaluating Keytruda vs. chemotherapy in 1st line NSCLC. This trial could provide context for understanding if chemotherapies are really needed for 1st line and whether patient selection based on PD-L1 status is needed.

Mixed data for MEK inhibitors

Roche presented P1 data for its PD-L1+MEK (atezolizumab+cobimetinib) combination in colorectal cancer in mismatch-repair proficient KRAS+ tumors.  The combination led to a 20% (4/20) response rate, which is not spectacular but significantly better than the expected ~0% in this population with either drugs alone. This study is important because it suggests that some drugs may be synergistic with PD-1 and that MEK inhibitors are potential “PD-1  potentiators”, as has been shown in preclinical experiments (it is still impossible to distinguish between direct anti-tumor activity and the alleged immunologic effect cobimetinib had). Although three patients were on study after 13+ months, the median PFS for the entire patient population was only 2.3 months (the only approved agent in this setting is Stivarga which demonstrated a PFS of slightly less than 2 months).

A P3 for the combination has been initiated based on these preliminary data. This is good news for Exelixis (EXEL) which has a 30-50% U.S. profit share, and double digit ex-U.S. royalties on sales of cobimetinib.

atezo+cobiArray (ARRY) presented mixed results for its MEK inhibitor (binimetinib) in NRAS+ melanoma. Although the drug increased PFS compared to chemotherapy, there was no overall survival benefit. While an approval based on PFS is still possible in this tough indication, binimetinib’s value proposition is probably limited as monotherapy. Combination with checkpoint inhibitors may provide a more attractive avenue, especially in light of Roche’s data with cobimetinib.

The next big event on Array’s horizon is P3 data later in 2016 for its second MEK inhibitor (selumetinib), partnered with AstraZeneca (AZN). The drug is being evaluated in KRAS+ NSCLC, which represents a $1-2B commercial opportunity.

Antibody drug conjugates disappoint…

Investors were disappointed with Rova-T (anti-DLL3 ADC), the primary asset of Stemcentrx for which Abbvie (ABBV) paid $5.8B upfront and $4B in potential milestone payments. Despite a 39% response rate in a subset of SCLC patients (n =26) with high DLL3 expression, the data set is still early and it is unclear whether activity will be corroborated in larger studies (see Immunogen’s case below…). If Rova-T eventually reaches the market in DLL3-high SCLC (less than half of SCLC cases), Abbvie’s cost would probably reach ~$7B, more than the market caps of Agios (AGIO), Bluebird (BLUE) and Ultragenyx (RARE) combined.

Immunogen’s (IMGN) update on its FRa ADC (mirvetuximab) was also disappointing with an updated response rate of 26% in the overall population (down from 35% at the last update). More problematic was the lack of correlation between FR expression and responses, which had been observed earlier and is now almost gone (See table below from RBC).  This led Immunogen to change its registration strategy and pursue regular approval in less advanced patients who (unsurprisingly) appear to derive more benefit from mirvetuximab. Without a biomarker defined subset of last line patients, development risk and timelines associated with this program are now significantly higher.

mirv - RBC

Seattle Genetics (SGEN) had a positive update for two ADC programs with Astellas (ASG-15ME and ASG-22ME), which generated a 28-32% response rate in bladder cancer.

…but naked antibodies shine

For anyone who has been following the antibody segment, ASCO 2016 provides an interesting observation about the therapeutic utility of naked antibodies compared to that of next-generation formats. Since the early 2000’s, the oncology industry shifted its focus dramatically from naked antibodies (like Herceptin and Erbitux) to “armed” formats such as ADCs and bispecific antibodies. Although the latter are orders of magnitude more potent, their clinical development has been plagued with issues like toxicity and short half-life, which in turn led to a very low success rate.

In contrast to the disappointing data with ADCs, this year’s ASCO included impressive data sets for two naked antibodies: Darzalex and IMAB362.

Genmab (GEN.CO) and J&J (JNJ) presented P3 results for Darzalex (daratumumab) in multiple myeloma, where the drug led to a dramatic increase in PFS (HR=0.39) when added to Velcade. Another trial evaluating Darzalex with Revlimid generated a similar effect with results expected later this month. Citi’s analyst Amalan R. Selvarajah now expects the drug to become a >$10B franchise (see figure below). Sanofi and Immunogen have a CD38 antibody with similar efficacy in P1 as monotherapy and in combination but development timelines with this antibody (isatuximab) are unclear.

Darzalex

Privately-held Ganymed presented a robust overall survival benefit for its anti-Claudin18.2  antibody  (IMAB362) in gastric cancer. The 161-patient trial evaluated IMAB362 when added to standard chemotherapy and demonstrated an increase of 4.8 months in overall survival (HR 0.51, p=0.0001). The benefit was even more profound in patients with higher expression levels of Claudin18.2.

Five Prime (FPRX) presented positive preliminary data for its FGFR2B+ antibody (FPA144) in gastric cancer. Of 9 gastric patients whose tumors express  FPA144’s target 3 had a PR and another patient had an early unconfirmed response.

Exelixis – Cabo established as a potential market leader

Exelixis presented P3 results for cabozantinib in renal cancer. As the drug already received FDA approval, most of the data had been released in advance, including a strong survival benefit (21.4 vs. 16.5 months, HR=0.66) and a clear win across all other endpoints. Last month, Exelixis announced another positive readout from a randomized P2 (CABOSUN), which evaluated cabo vs. Sutent in 1st line RCC. No numbers were given but the company disclosed that cabo led to “a statistically significant and clinically meaningful” improvement in PFS. This is the first time any drug beats Sutent in 1st line RCC, which could eventually support utilization in 1st line RCC ($1.5B opportunity).

As an oral drug with a better HR than Opdivo (0.66 vs. 0.73), a clear win over Sutent in 1st line, and significant improvements in response rate and PFS, cabo should become a (if not the) leading treatment option in renal cancer. Recent strength seen with the stock reflects increased investor confidence about cabo’s market positioning vs. Opdivo. For the rest of 2016, investor focus will be on the US launch (approved since April 25), EMA approval (expected imminently), CABOSUN data, a licensing deal in Japan and a restructuring of Exelixis’ long term debt which is still a major overhang.

Biosimilars expand into oncology

This year’s ASCO saw the first head to head P3 for a biosimilar antibody, Mylan’s (MYL) version of Herceptin. The biosimilar was compared to Herceptin in a 456-patient trial and demonstrated similar efficacy (response rate) and safety profile. Mylan plans to submit its Herceptin biosimilar, which is already commonly used in India, to the FDA this year but it is still unclear whether it will be allowed to launch the drug in the US before 2019. This is probably the first of many attempts by biosimilar companies to capture market share from Roche’s three leading biologics: Herceptin, Rituxan and Avastin (combined annual sales of $20B). Of the three, Avastin looks like the most vulnerable one with no apparent successor in Roche’s pipeline.

59 thoughts on “Notes from ASCO 2016

  1. Thanks Ohad
    nice summary. Interesting point you make about how naked antibodies are so successful, and everything else has its growing pains! Regarding ARRY, would you expect them to try to partner their MEK with anti-pd(l)1 therapeutics soonish? Who would be the most likely partner? What do you think of their triplet ph3 announcement (erbitux)?
    Thanks
    Dan

  2. Hi Ohad,

    EXEL: Exelixis looks like a big winner at this year’s asco. Especially impressive were the much superior HRs vs Everolimus in both PFS and OS for patients with mets:

    Bone: PFS 0.33, OS 0.54
    Visceral+Bone: PFS 0.26, OS 0.45

    Its superiority to Nivolumab in this sub-population seems to be validated both by the size of the effect given size of the subgroup in METEOR, and the mechanism/previously seen activity of Cabo. Interestingly, Nivolumab seems dramatically better for patients w/ poor MKSCC risk and Cabo better for thos with favorable/intermediate.

    Do you have a new price target for EXEL with the approved RCC only? Any thoughts about chances of success in HCC and a price target if they are approved there?

    IMGN: I believe the RBC slide is slightly misleading as it lists only confirmed responses and gives no credit to the duration or size of the responses at maximum. I think the signal’s been a bit diluted but it’s not as dramatic a dilution as what they seem to indicate. Here’s a comparison picture of the spider plots and waterfalls for you with the November figures on the right:

    http://s33.postimg.org/mmq3e5eof/8c5f2c97_6baa_400f_be18_461afc7c5bec.png

    Medium and high patients still seem to be the majority of those with any response at all and deep responses.

  3. *What I mean is “any shrinkage at all”, not “any response at all.”

  4. Dan – Thanks. It’s like naked antibodies are failure-proof but there are sufficient examples where they are doing a great job (Herceptin, Drazalex, Gazyva).
    Re: ARRY – I am sure they will do combination studies with PD-1/PD-L1 antibodies but they don’t need to partner as 3 agents are already approved (they might consider collaborating with a PD-1 company for cost savings). I think the triplet trial in BRAF+ CRC makes sense but still far away. All eyes are on SELECT-1.

    Wildbiftek
    EXEL – If they land a good Japan deal and remove some of the debt I think EXEL can easily find itself around $10-11. Liver cancer is very tough but I am cautiously optimistic now, this could be a huge upside with $1+B in potential sales.
    IMGN – Agree about confirmed responses not capturing milder degree of tumor shrinkage, still this is a more reliable and rigorous endpoint.

    Ohad

  5. IMGN: I agree w/ your comment; after the CLVS debacle confirmed responses seems to matter most when considering RECIST responses but even with just that the agent still seems quite active.

    It’s strange that there hasn’t been a peep out of Sanofi regarding their CD38 mab. There’s also the Biotest CD138 targeted ADC that may be moving forward this year, although they may want to sell off that asset for cash to develop IMGN853.

  6. Hi Ohad, Great summary!

    What do you think of Progenics Pharmaceuticals(PGNX)?

  7. $EXEL Picking up on your last line : Of the three, Avastin looks like the most vulnerable one with no apparent successor in Roche’s pipeline. Don’t you think that if Avastatin has no clear successor, the combination trial of Avastatin and atezzo by Roche in RCC against sunitinib as the control is futile given that Cabo is now on the verge of going into first line. This should make Roche cough up some mega mega mega dough to buy Exelixis. Roche is more vulnerable revenue wise, it just makes total sense to buy Exelixis so that they don’t have to hide Cobimetinib success stories, and secretly launch P3 trials under the hood. They are also now being challenged on the pricing by Exelixis, and if the arbritrator awards more dough to Exelixis, ouch..on the wallet. They need to stop being penny wise foolish. Please tell my why it would not make sense for Roche to buy Exelixis out. I want to know if i am missing something.

  8. $EXEL I have read on a blog post on yahoo that they(Roche) have other websites where they recruit patients for clinical trials when they don’t want to be so public. In general I suspect Roche of having more data about Cobimetinib success that they are not willing to reveal. I cannot make a claim but this is based on a hunch, and information on the message boards.

  9. Atezolizumab + bevacizumab & nivo + ipi both show about 40% ORR in 1st-line RCC trials.

    It’s highly unlikely that Cabozantinib would be able to complete with IO combo as single agent. And anti-PD1/PDL1 +TKI combo will be problematic because pts would became refractory to both IO & TKI after tx failure.

  10. Wildbiftek (IMGN) – Indeed , CLVS’ case was an important lesson. At least IMGN has been transparent and honest in real time and in contrast to CLVS, it has no competition.
    Agree about Sanofi’s CD38 program, they are missing precious time and if they choose to pursue this mAb (which I think they should), they’ll probably have to do head to head studies vs. dara.

    Ohmsonite (EXEL) – Thanks. Their observation make sense given what we know about superior near term anti-tumor response with cabo whereas nivo exerts its effect later after therapy.

    Kelvin (PGNX) – Thanks, haven’t been following them.

    curiousgeorge (EXEL) – RCC is not an important market for Avastin (primary markets are lung and colon). I don’t think atezo+Avastin in RCC is futile, it all depends on the data. I don’t think a company can “hide” late stage trials, they need visibility in order to attract patients/physicians.

    wfd (EXEL) – There a lot of open questions and imo there isn’t enough information to reach a definitive conclusion (note the figures we have for combinations is from small non-randomized trials). The issue of resistance is not that straightforward as well, patients who fail Sutent (VEGFR inhibitor) do not necessarily do better on non-VEGFR treatment as 2nd/3rd line. Same goes for IO as we saw in Yervoy failures who got PD-1. Again, a lot of moving parts…

    Ohad

  11. Hello Ohad,
    did you see yesterday’s investor presentation by ARRY?
    The Kaplan Meier graph for PFS in post immunotherapy patients for binimetinib in NEMO looks quite amazing. Almost 20 % patients with Bini long progression free, app. 18 months. Post IO will be the target population, anyway. No effect by DTIC, though. They revealed it from app. 90 patients. So it should be quite solid. I don’t think the FDA will ignore this.
    What do you think?

  12. Ohad,

    Could you compare IMGN and SGEN and try to determine why SGEN should have a market cap that’s well over ten times that of IMGN.

    Thanks,

    Gary

  13. SAGE / MRNS

    Hi ohad,

    Are you still long both stocks ?

    SAGE had huge insider selling over the last couple of months. There is also much pressure from shorts like chardan, which make the stock going lower.

    MRNS : readout in FXS is a very high risk event .do you plan to accumulate more shares if the trial fails and stock goes down?

    Thank you in advance for answering my questions. I appreciate your work .

    N0c

  14. Hi Ohad,

    Quick question about the EXEL 4.25% Bonds due in August 2019. My understanding from the prospectus is that the bonds are convertible by EXEL after 08-15-2016 for cash (as long as the stock trades at 130% times $5.31 (equals $6.91) for a certain period). The bonds DO NOT appear to be convertible by the holders until 05-15-2019 (unless a buyout occurs and the holders get cash to repay the bonds plus accrued interest).

    Just wanted to confirm this with you as I am trying to determine what the LT value of EXEL and am attempting to determine what their proper shares outstanding will be. I would like to confirm my understanding that the convertible bonds cannot be converted at $5.31 by the bondholders until 05-15-2019.

    Between 08-15-2016 and 05-15-2019 I am hopeful that EXEL will be able to pay the bonds off in cash. This would alleviate a potential 60mil share dilution from the bondholders converting (at an exchange of $5.31/shs) which would presumably be substantially lower than the stock price.

    Per the prospectus:

    “The notes will be convertible by the holders beginning on May 15, 2019, or earlier upon the occurrence of certain events (BUYOUT). The notes will be convertible at an initial conversion rate of 188.2353 shares per $1,000 principal amount of notes ($5.31/shs). The conversion rate will be subject to adjustment upon certain events, but will not be adjusted for accrued and unpaid interest. Upon conversion, the notes may be settled, at our election, in cash, shares of our common stock, or a combination of cash and shares of our common stock.

    We may redeem some or all of the notes for cash under certain circumstances on or after August 15, 2016. If we undergo a “fundamental change”, holders may require us to purchase the notes in whole or in part for cash at a purchase price equal to 100% of the principal amount plus accrued and unpaid interest.”

  15. CL (ARRY) – The higher PFS in pts who received prior immunotherapy is intriguing but as a subset analysis it has to be validated prospectively. Also, how does OS look like for the same breakdown?

    Gary Mohilner (SGEN/IMGN) – SGEN has US rights for Adcetris and a potential to achieve >$500M in US sales + royalties on global sales. In order to reach a valuation of several billion, IMGN needs to have marketing rights for a program with clear route to market and high likelihood of success. Mirv could have provided that but recent data make this program riskier.

    Noc (SAGE/MRNS) – Yes I am still long both stocks going into important readouts later in the year. For MRNS, I don’t have high expectations for the FXS study but am cautiously optimistic about P3 in partial onset seizure study. SAGE should have randomized data in post postpartum depression, which I expect to be positive based on their pilot study.

    Steve (EXEL) – Don’t think this will impact cabo’s fate in 1st RCC. The need to differentiate PD-1 mAbs with combinations could bode well for a drug like cabo but it’s hard to speculate without clinical data (so far similar combination demonstrated tolerability issues).

    Justin (EXEL) – Yes that’s my understanding as well. EXEL can call the 2019 convertible notes after 8/15/16, if the stock is >$6.90 for 20 out of 30 consecutive trading days. This means the company needs to wait at least 2 months before paying the debt back assuming the stock stays around current levels.

    Ohad

  16. Hello Ohad,
    thanks for the comment!

    Post IO OS in NEMO by Bini was not provided in that presentation. However, the CEO of ARRY explained why the OS difference between DTIC and Bini narrowed in the final data. Quite a few patients after progressing on DTIC were put on immunotherapy. It is understandable that these patients were not left to die as a control group. That might be the reason why DTIC OS was app. 10 months and only roughly 8 months were anticipated. Thus, it would be misleading to look at OS in NEMO. I don’t think, that the ARRY shorts took that into account so far.

  17. Hey Ohad
    MRNS! disappointing. But you had called it. High risk. Listen, do you think one of the challenges with Ganax is the bioavailability? Considering that they have developed IV and that in spite of raising the dose in Ph3.
    Thanks. What are your expectation regarding the two orphan indications? results will be announced imminently, any chance of a surprise? And where does this leave MRNS considering SAGE is way ahead in SE?
    Thanks
    Dan

  18. I think the recent MRNS failure decreases the likelihood of SAGE success in SRSE. While I think the drugs are effective, I dont believe they are superior to approved treatments. I think the major problem in this population and in SRSE is that a large majority of these patients will have been exposed to many compounds that reduces the efficacy of extra-synaptic GABA activation due to changes in receptor localization and sensitivity. Best indication would be for 1st line use in SE possibly RSE. I now doubt SAGE will reach primary endpoint. The decision to wean off treatments and impulse to restart them is very hard to to control in that setting.

  19. Hi Ohad,

    Any thoughts about IMGN’s proposed convertible debt offering of $100mm senior secured notes due 2021? It’s modest given their clean balance sheet, and it should buy them about 2 extra quarters of burn but it generally seems like they have their fingers in too many pies running so many other trials with 779, 529, exploratory trials with 853 on other tumor types, combos etc. as well as research. I understand the rarity of their technology and laying off workers may be akin to killing the goose that lays the golden eggs but surely running a leaner set of operations until they get a reliable stream of money would help. (Or do you already expect that?)

  20. Christian/Alex/Dan (MRNS) – There could always be a surprise in FXS, which is a randomized trial but other than that I don’t see any near term catalysts. Longer term, IV ganaxolone could be relevant for SE but P1 hasn’t started yet so we can expect data in patients only next year. I don’t know if they have an oral bioavailability problem but even as an IV drug, ganaxolone could be as effective as SAGE-547 (although it’s several years behind). I don’t plan to average down.

    CL (ARRY) – Post study treatment tend to have an confounding effect but from what I understand a significant portion of patients in the bini arm went on to receive PD-1.

    jh (SAGE) – Given the different indications and data sets I don’t think MRNS’ failure has significant read-across to SAGE. Obviously, SAGE is still a high risk investment but I plan on holding.

    Wildbiftek (IMGN) – Raising debt at this time is disconcerting and will become a serious overhang imo. It may be the prudent thing to do but market reaction isn’t going to be pretty….

    Chris (TRVN) – Yes I plan to add more TRVN, not sure about the timing as their P3 data are expected next year.

    Ohad

  21. Hello Ohad,
    thanks for sharing your thoughts on ARRY!

    Even if the Bini group was also treated with immunotherapy after progression, the statistics for OS would be screwed up, because one cannot assume that immunotherapy after Bini has the same effect as after DTIC. My point is that OS will not be the pivotal reason for the FDA decision. They would have to ask for clean controls which is ethically not possible if there are alternative treatments.

  22. Hi Ohad,

    IMGN: Well you were right about the market reaction to the secondary. My biggest concern right now is that they didn’t raise enough money to make ends meet through a FORWARD I readout without cutting other programs or laying off research staff. Could they be holding out for a higher share price when any number of potential catalysts materialize? (FDA BTD for MS in EOC, new partners, existing partner trial successes/milestones/royalty monetization, FORWARD II results) Any thoughts?

  23. Ohad, what do you make of EXEL strong rise over the past two weeks? Ipsen raised 300 euros this week -new trials to be announced soon? How likely is it FDA allows 1st line approval on CABOSUN? What is peak estimates for HCC sales if p3 is positive?

  24. “At the meeting, BMS (BMY) presented data for this combination in SCLC and gastric cancer but in both cases results were underwhelming and the combination appears only slightly better in SCLC (overall survival of 6-7.7 months).”

    Underwhelming? Really? You are looking at the new standard of care in NSCLC.
    In SCLC 1 year survival in combo using 3mg of IPI plus 1mg of Opdivo 43% vs 33% with Opdivo alone. 10% response rate vs 23%. Isn’t it a bit premature to label this combination underwhelming?

  25. TRVN ? Looking at phase 3 design and really dont understand the rationale of testing 3 different doses. IMO primary endpoint of pain relief compared to placebo is very easily obtainable in a small number of patients testing a single dose. Do you think this trial design is in response to FDA comments?

  26. HI Ohad,

    Any thoughts on GNCA following their recent presentation?

    Thanks,
    Chris

  27. $MRNS What do you think of the Fragile X data ? Worked for anxiety related but did not meet the overall endpoint. Some analysts think it has a bioavailability problem after the P3 failure in focal onset.

  28. $SPHS What do you think of this company with good P1/2 data ? They are in prostate cancer field.

  29. Does the latest success for p3 niraparib from TSRO mean that rucaparib from CLVS is now behind? Time to sell CLVS?

  30. CL (ARRY) – Agree that bini may be approved without OS benefit in this indication, still, in order to become an attractive drug ARRY needs to combine it with PD-1 imo.

    IMGN (Wildbiftek) – If they had an important near-term catalyst they would have probably waited with the fundraising. There can always be positive surprises from partnered programs (NVS, LLY) but timing us unpredictable.

    David (EXEL) – EXEL is particularly strong (for a change…). Hard to tell what is behind this, perhaps people see signs of a strong launch in RCC. Not sure about likelihood of approval in 1st line RCC based on CABOSUN, was originnaly very skeptic but Lenvima could serve as a precedent. HCC market could be a $1B opportunity, depending on treatment duration.

    SAMi (IONS) – Too much uncertainty for me and looks like competition in TTR and SMA (ALNY and AVXS, respectively) is superior to IONS’ programs.

    scott – Hope you are right but from where I sit these data are not that exciting because by definition the survival benefit is not dramatic.

    Alex (LIFE) – They should have data in FSHD and LGMD in Q4. Don’t know OCUL.

    Jh (TRVN) – i actually think it’s a great idea to have several doses as there is very low tolerance to safety events in this setting (see recent case with CARA). Post-surgical pain are relative quick and cheap so there shouldn’t be a major impact.

    Chris (GNCA) – Still didn’t have a chance to review.

    Bouschka (ESPR) – This is definitely a serious blow (and the way they communicated it didn’t help either…). I still believe the drug is promising and hopefully CVOT data with PCSK9 antibodies will help FDA feel more comfortable with LDL-C as a surrogate endpoint.

    curiousgeorge (MRNS) – The Fragile X study failed, hard to interpret the subset analysis presented by the company imo. Don’t know SPHS well.

    Minh Tu (CLVS) – IMO this is bad news for CLVS because the data are so striking in BRCA and HRD+ subsets. It means CLVS will see very strong competition.

    Scott/lgonber (ESPR) – Still trying to make up my mind whether to sell or not… I still think they have a statin-like molecule that could eventually, despite the recent interaction) get FDA approval based on LDL reduction if PCSK9 CVOT turn out positive.

    Will try to publish a new post on Sunday.

    Ohad

  31. Hey Ohad

    regarding ESPR – it seems they have hinted in last press conference that they are actively considering EU (or ex-US) deals. Would that help shore u confidence and share price?
    Would it not be better to keep patient at this juncture?
    Thanks
    Dan

  32. One more question… Any opinions/updates on AUPH–they released interim analysis on first 7 patients dosed.
    Thanks

  33. Thanks for your reply. Regarding ESPR I believe they will sell the company to a Japanese or even European company before they have to raise money for costly long CVOT studies. Japan and European markets might be better after FDA comments. Something is up with FDA and statin lobby. Remember the Vascepa from Amarin case…

  34. Ohad
    any thoughts about BGNE BTK+PD-1 program. They are behind INCY+MRK but at least they own both components.

    Do you follow also the SYRS IPO. Interesting target, if they prove to be valid.

    Thanks

  35. Ohad: is TSRO the next MDVN or Incyte? $10b company with ovarian and breast cancer…? Buy?

  36. Dan (ESPR) – I think they don’t have a choice, they cannot wait until they have P3 LDL data but need to partner now (at least EX-US).
    AUPH – They should have data very soon, don’t think the remission rate from a 7-patient cohort can be used for predicting results in a large randomized trial. I intend to hold going into data readout (high risk event hence the small exposure), same goes for ARRY.

    Lgonber (ESPR) – I guess this is the direction they are pursuing right now.

    andre (BGNE) – Combining PD-1 and Btk inhibitors obviously makes sense but they will face a lot of competition from Imbruvica and AZ. Not sure this will compete directly with INCY/MRK’s PD1+IDO combo where focus is more on solid tumors.
    Re SYRS – I think the science is very interesting, I like the super-enhancers story very much but as you suggested still early (I like the CDK7 program better).

    Joe (TSRO) – Data were awesome! still trying to understand whether their molecule is differentiated than olaparib and other PARPi. Looks like there are some differences mechanism-wise (trapping vs. catalytic inhibition) among some of the molecules.

    Ohad

  37. What did you think about ARQL’s results in intrahepatic cholangiocarcinoma?

  38. Richard (ARQL) – There’s clearly activity but not sure it’s sufficient to pursue accelerated approval. Given the huge unmet need, perhaps they can get approval as monotherapy but combination may be a more viable route.

    Ohad

  39. Hi Ohad,

    What do you make of EXEL’s volume the past two trading days? On 06/30/16 it was over 16mil shares than 22mil on 07/01/16. Avg volume is around 5mil shares. Potential suitor acquiring a stake behind the scenes pending a buyout offer?

  40. hey Ohad
    first time i saw you use AWESOME. Does that mean you are going to buy TSRO?
    Dan

  41. Justin (EXEL) – I don’t think there is anything of that sort going on. Companies had an opportunity to buy EXEL after the OS data so now a potential acquirer will probably wait to see how the drug performs in the market.

    Dan (TSRO) – Not sure yet, a lot depends on whether all PARP inhibitors are interchangeable.

    Ohad

  42. Hello Ohad ! A while back you were considering adding FOLD. Any new comments?

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