Biotech portfolio update – Jumping into gene therapy

After a long summer break it is time to review recent events and update the portfolio. As far as clinical readouts go, my portfolio had a brutal summer with one complete P3 failure from Array Biopharma (ARRY), a mixed data set from Aurinia (AUPH) and a win from SAGE (SAGE) that resulted in limited share appreciation. This was offset by strong performance from Exelixis (EXEL), my biggest holding which is up 48% quarter to date.

For the remainder of 2016 I plan to gradually increase exposure to gene therapy, which I hope will become one of the industry’s primary growth drivers in the coming years. In parallel, as I am still pessimistic about the biotech field in general (R&D productivity, pricing, biosimilars…), I intend to keep my short ETFs and a significant cash position.

Data readouts – Array and Aurinia disappoint, SAGE delivers

Array Biopharma – Astrazeneca’s (AZN) selumetinib, originally developed by Array, failed to improve PFS or overall survival in KRAS-mutated lung cancer. This P3 failure demonstrates once again the challenges in corroborating positive P2 data and joins a series of disappointing news for MEK inhibitors. In 2015, selumetinib failed another P3 study in uveal melanoma and earlier this year, Array terminated a P3 study for its wholly-owned MEK inhibitor, binimetinib, in ovarian cancer. Recent P3 data for binimetinib in NRAS+ melanoma was technically a success but benefit was underwhelming (improvement in PFS without a survival benefit).

MEK inhibitors are still being explored in multiple indications that may enable developers to expand their use beyond BRAF+ melanoma. At ASCO 2016, Roche and Exelixis reported an intriguing efficacy signal with Cotellic in KRAS+ colon cancer. Another indication that is not discussed much is neurofibromatosis type 1 where selumetinib demonstrated strong efficacy but timelines and registration strategy are not clear. Later in 2016, Array will report data for binimetinib in BRAF+ melanoma, where two other MEK inhibitors (Mekinist and Cotellic) are already approved. Array hopes to demonstrate a differentiated safety profile but penetrating the BRAF+ market is going to be challenging.

Aurinia – Aurinia reported results from a P2b evaluating two doses of its calcineurin inhibitor (voclosporin) in lupus nephritis. While voclosporin demonstrated superiority over the control arm at the low dose in inducing remission (32.6% vs. 19.3%), there was no effect with the high dose and there was an alarming imbalance in deaths between the low dose cohort (13 cases overall, 10 of which occurred  in the lower dose arm). The fact the active arm had such a high mortality obviously raises safety concerns but also casts a shadow on the efficacy signal and trial design.

SAGE –SAGE reported a strong efficacy signal for its lead program, SAGE-547, in a placebo- controlled P2 in postpartum depression (PPD). Despite the typically high placebo response in depression trials, the drug led to a clinically meaningful reduction in depression with a ~12 point reduction from placebo on the HAM-D scale. Importantly, the effect had a quick onset and appears durable almost a month following treatment cessation.


These results are very significant for SAGE-547 because they validate the initial signal observed to date in single arm open label trials or case studies, which are rightfully viewed as unreliable (especially in CNS indications). Despite the small sample size, the strength and consistency of the PPD data imply the drug is active and de-risk the program.

Going forward, SAGE decided to focus on SRSE with SAGE-547 (P3 data pushed out to 1H:2017) while pursuing PPD as well as other CNS diseases (essential tremor, Parkinson’s) with a next-generation oral drug (SAGE-217). This decision makes sense in light of the different clinical settings (SRSE patients are hospitalized and need immediate solution for their seizures whereas PPD may require more prolonged treatment). SAGE-217 appears more potent and selective than SAGE-547 with good pharmacologic profile based on P1, but it is still not validated in the clinic.

Momentum continues to build around gene therapy

There have been some notable news in the gene therapy space including three data readouts and an acquisition. This gradual but consistent progress helps to build confidence around gene therapy and makes it one of the most important segments in the industry.

The combined recent data set from all gene therapy companies still comprises less than 100 patients with limited follow up, but for the first time in more than 25 years, we are starting to get positive answers on three major questions: Efficacy, durability and safety. With tens of active clinical programs, strong data across multiple domains (liver, CNS, retina, bone marrow) and an armamentarium of tissue-specific vectors, gene therapy may be ready for primetime. The field will surely see its share of failures but the path to commercial success with gene therapy is finally visible.


Biomarin (BMRN) made a big splash with its hemophilia A treatment, BMN-270, demonstrating that gene therapy can lead to a functional cure (at least for a period of time). Results from 7 patients treated at the highest dose demonstrated quick and robust expression of factor VIII (hemophilia A is caused by low factor VIII activity). Strikingly, all but one patient achieved normal levels and this was accompanied by a dramatic reduction in bleeding events despite taking patients off prophylactic FVIII treatment. Follow up is still limited (up to 20 weeks) but Factor VIII production appears to be stabilizing or even increasing in some cases.


The study was a major win but there were two safety signals:  ALT elevation (marker for liver damage) and an above normal FVIII levels in two patients.

ALT elevations are closely watched in every liver-targeted gene therapy study because earlier products led to ALT elevations (probably an immunogenic response against the viral vector) that led to clinically relevant elevations and were associated with loss of transgene expression. There is still not enough follow up to rule out any chronic liver toxicity but according to Biomarin, the ALT elevations were not clinically meaningful and appear to be manageable with steroids (in some cases patients were taken off steroids and liver functions returned to normal). Fortunately, the ALT elevations do not seem to correlate with loss FVIII expression as production continued to rise or stabilized during these events.

The excessive FVIII levels in two patients are troubling on paper (especially if production keeps going up) because elevated levels of FVIII are associated with higher risk of thrombotic complications according to several studies, reviewed here. This demonstrates a primary concern with gene therapy – it’s irreversible and cannot be “switched off”. While the company disclosed patients are not experiencing any thrombosis-related events, they will have to be monitored and potentially treated in case FVIII continue to climb or any abnormalities emerge. Going forward Biomarin plans to evaluate a lower dose to avoid such cases.

Overall, Biomarin’s hem A data are impressive and together with data from hemophilia B programs from Spark (ONCE)/Pfizer (PFE) and UniQure (QURE), they lay the groundwork for registration programs in hemophilia potentially next year.


While Biomarin’s gene therapy for hemophilia demonstrated both protein production (FVIII in the blood) and clinical improvement (bleeding incidence), Avexis’ (AVXS) AVXS-101 demonstrated only the latter. Nevertheless, the dramatic clinical signal coupled with the fact that the target tissue are neurons make AVXS-101 one of the most important gene therapies in development (and personally speaking, the most intriguing one).

Last month, Avexis provided an update from a clinical trial evaluating AVXS-101 for SMA1, a fatal disease in infants that affects the motor neurons and is invariably fatal by 2 years of age. Following the previous data readout (which I discussed here), the clinical effect appears to hold with unprecedented functional and survival improvements over historical data. All but one patient on the high dose cohort had a dramatic functional improvement vs. the expected persistent decline that is the hallmark of SMA1. Importantly, none of the patients had an “event” (defined as ventilation or death) despite crossing 8 months of age where a recent study showed an event rate of 50%. Duration of the effect is still unknown due to limited follow up (appears to be at least 1 year).

AVXS101The trial did not have a control arm but the difference is so dramatic that I find it hard to believe it is just a statistical artifact.  The recent breakthrough therapy designation the FDA granted to AVXS-101 is another testament to the robustness of the data. Biogen (BIIB) and Ionis (IONS) reported P3 success for nusinersen in SMA1, which validates the signal observed in a previous single-arm study and this strengthens the notion that single-arm trials in SMA1 can generate a reliable signal. Although nusinersen can theoretically be seen as a competitive threat to AVXS-101, if both drugs are approved, nusinersen will probably be used on top of a one-time gene therapy like AVXS-101.

AVXS-101’s effect, if real, implies that AAV9 vectors Avexis utilizes can cross the blood-brain-barrier and reach the central nervous system. This could have dramatic implications for many rare genetic diseases (and down the road more prevalent diseases like Parkinson’s and Alzheimer’s disease) where the nerve system is damaged but cannot be modulated by existing drugs. In this perspective, companies like REGENXBIO (RGNX) and Abeona (ABEO) are very interesting opportunities as both target neurologic diseases (or ones with neurologic manifestations) with AAV9-based gene therapies.


Spark reported updated results from its pivotal trial for its RPE65 gene therapy (Voretigene neparvovec) for inherited retinal disease. The study was overwhelmingly positive and will likely be the basis of the first ever FDA approval for gene therapy next year. In contrast to other gene therapy programs in development, Spark’s program has up to 3 years of follow-up and so far the effect appears to hold.

RPE65 gene therapy is to retinal diseases what hemophilia gene therapy is to liver diseases – a proof of concept that paves the way for other genetic retinal diseases like XLRS, XLRP, achromatopsia and choroideremia. Spark will have first clinical data for its choroideremia program later in 2016. AGTC (AGTC) is expected to report initial clinical data in XLRS and achromatopsia also in 2016.

Spark also has a Hemophilia A program (SPK-8011), which is about to enter P1. Despite being more than a year behind Biomarin, recent results for Spark’s Hemophilia B program (partnered with Pfizer) were very encouraging and may point to some advantages with Spark’s vectors. These include better potency and lower immunogenicity that could translate to a more compelling clinical profile (i.e achieving the required protein levels with limited immune reaction, and down the road better durability and dosing flexibility).

Pfizer acquires Bamboo

One item that went relatively unnoticed is the acquisition of Bamboo by Pfizer. Bamboo is developing gene therapies for neuronal and neuromuscular indications with a program in P1 for Giant Axonal Neuropathy. Despite the modest deal size ($150M upfront), it is an important milestone in big pharma’s venture into gene therapy, which historically has not been aligned with the pharma business model (one time genetic treatment vs. recurring sales of small molecules or biologics). The title of Pfizer’s press release (“Pfizer aims to become industry leader in gene therapy with aquisition of bamboo therapeutics”) clearly demonstrates this trend.

If gene therapy is indeed going to become a central component of the biopharma industry, the demand for validated platforms with clinical data and CMC capabilities could grow dramatically in the near future. In contrast to cell therapies such as CARs and TCRs, gene therapy may be more palatable to pharma because the end product is still a drug in a vial and not a process.

Portfolio updates

Given the early stage and inherent risk in gene therapy, I intend to build a diversified portfolio with the goal of starting 2017 with 7-8 stocks that will comprise a third of the portfolio. Today I am starting with Spark, Avexis, REGENXBIO and Abeona  (Next on the list is Bluebird going into ASH 2016…)

I am selling Array Biopharma, Aurinia, Genocea (GNCA) and Conatus (CNAT). In addition, I am selling part of my ArQule (ARQL) and Foundation Medicine (FMI) position.

Lastly, I am initiating a small position in Kura Oncology (KURA) following an early signal in HRAS+ H&N cancer.

Portfolio holdings – September 4th, 2016

Portfolio holdings - 4-9-2016 - after changes

biotech etfs - 4-9-2016

134 thoughts on “Biotech portfolio update – Jumping into gene therapy

  1. THANKS OHAD ! THREE QUESTIONS ? What caused KURA to fluctuate from 3ish to as high as 25? Will you provide some background on why you have included them in your portfolio? Will you be eventually including QURE in your portfolio? THANKS in advance.

  2. Hi Ohad,
    Thanks for the write up.
    Can you please expand on why you exited CNAT and GNCA? What’s your price target for EXEL?

  3. Ohad
    Re. AVXS. Nusinersen completed Ph 3 and BIIB/IONS are preparing marketing applications. They also have orphan drug status which may block future competition.
    Also AVXS may have to use Nusinersen as comparator, which could further complicate their trails.
    According to their presentation the next catalysis is 13.6 months data from Ph 1 in SMA 1 (Q1 2017) and initiate pivotal trail in H1-2017- it does not look an eventful calendar.

  4. Hi Ohad

    ONCE: Given the current market cap of already USD 1.8bn, don’t you think that upside is quite limited from here?

    Many thanks

  5. Ike (GNCA) – Honestly, it falls outside of my areas of interest and I didn’t feel I have enough knowledge to analyze it. The neo-epitope endeavor they announced is very intriguing but very early.

    Bouschka –
    KURA – Not sure about price fluctuations but probably related to the public offering they did in Nov. Yes, I will try to delve deeper into the story. Basically it’s still an early stage risky stock but they might have identified a small population (HRAS+ head and neck) that are sensitive to tipifarnib that could be pursued with accelerated approval. Early days though with only 3 pts…
    QURE – Not sure… On the one hand they are traded near cash but on the other I am not sure the Hem B program is competitive enough and their Sanfilippo B program might face competition from IV gene therapies (AAV9). Deal with BMS is a plus.

    Alex –
    ARRY – Correct and I had high expectations from day one but apparently I was wrong
    LIFE and FOLD are still on my watchlist. I prefer to see how the EU launch goes before jumping into FOLD and LIFE I plan on adding later this year.

    GNCA – See my reply above
    CNAT – Clinical data were mixed
    EXEL – I think that with the current labels for their products (cabo+cobi) the stock cannot go much further (assuming a market cap of ~3.5B). Positive 1st line RCC data at ESMO or positive P3 readout in liver cancer could push the stock towards 15 and 20+, respectively IMO.

    andre (AVXS) – I am not concerned about nusinersen because AVXS’ data are so spectacular that I believe many parents would opt for their clincal trial (agree that design is unclear and creates uncertainty). Orphan drug designation cannot block other drugs, only generic versions of nusinersen. Agree about the quiet calendar but I plan on adding more if the stock goes down.

    Kevin (ONCE) – Agree that valuation is lofty if you include only RPE65 and HemB royalties. I think that their platform+capabilities+ additional propritary programs justify a significant premium. Same with AVXS, I view ONCE as a core holding and plan to average down if given the opportunity.

    Emmanuel (BLUE) – Very hard to predict. Hope they’ll show better transduction in b0/b0 and SCD but my guess is as good as anybody else’s.


  6. OHAD…I am very interested in Syros! The Science,Scientific Founders,and Management are all equally impressive! There recent press release on their CDK 12 and CDK 13 selective inhibitors was VERY intriguing. Would they be a candidate for your new Gene Portfolio?

  7. $EXEL I think it will go to 20 by ESMO of this year, you are underestimating it. This is like MDVN except Exelixis has more eggs in the basket than MDVN. Celestial positive should bring it higher. A possible buyout after that brings it even higher.

  8. Bouschka (SYRS) – Totally agree. Scientifically speaking, a very interesting approach, a lot to explore in the “neglected” transcriptional CDKs and SYRS has the underlying technology and understanding to do this imo.
    They are not a gene therapy company but I will keep tracking them going into 2017.

    curiousgeorge –
    LIFE – Yes I prefer to see updated results hoping to see a direction in some efficacy metrics.
    EXEL – I don’t see the stock goes to 20 based in 2nd line RCC alone, they need to expand the label for that.


  9. Hi Ohad
    what are the less optimistic scenarios for EXEL ?
    AERI – Im considering to buy , whats your opinion?
    ARRY –
    SunTrust analyst Peter Lawson says that the Phase 2 data for Array BioPharma’s ARRY-797 was “encouraging.” The analyst reports that patients taking the drug showed greater improvement in a 69 minute walk test than those taking approved drugs. He believes that Array’s drug can be “part of a $150M-$300M market opportunity.” The analyst reiterates his $7 price target and Buy rating on the shares

    Why you decided not to wait?


  10. $EXEL We shall see, CaboSun will take it to 20, they will do 1st line in RCC with CaboSun.

  11. If the GBT data continues to show a positive effect I don’t see how BLUE succeeds as a sickle cell therapy. Huge cost discrepancy between the 2 therapies and there is a big safety issue with BLUE which has to start out by destroying the old in the marrow before inserting the new. Smart guys with a lot of cash but imo they would be better off if they focused more on their cancer therapy.

  12. Alex (EXEL) – Less optimistic scenarios are: bad CABOSUN data, HCC failure and significant tox in the PD-1 combination study. Still, I don’t envision anything that can prevent cabo from being a $500-700M drug.

    AERI – haven’t been following for a while
    ARRY – I just decided that the risks outweigh the upside at the current valuation. Not guarantees there of course…

    curiousgeorge (EXEL) – Hope you are right but it will have to pass in flying colors in order to become a viable 1st line option.

    Alex (MRTX) – MRTX had disappointing data especially in light of Xalkori’s recent results in MET+ NSCLC.
    DRNA are very cheap, no doubt. Don’t have a concrete opinion though

    mike guiltinan (BLUE/GBT) – It depends on the data. If BLUE can offer a one-time treatment with a reasonable safety profile I think a lot of patients will opt for it (many do allo transplant which is much more dangerous). But first they need to show efficacy…


  13. ruhu (EXEL) – IMO that’s bad news and decreases likelihood of success. For Stivagra, positive readout was achieved after 3 years with a smaller study (although we don’t have actual number of events and recruitment rate).


  14. Hi Ohad, thanks for your portfolio. I am currently reviewing several GT companies too. I have similar comments to the others regarding ONCE, as valuation is quite high, nevertheless it is in my watch list in case there is a dip at some point that let me get in before their product is approved.
    I am also interested in AVXS, can you comment on their vector administration? The viral vector used in systemic (IV) administration requires a 10X higher dose than in the inferior intrathecal method and dose is also subject to weight. I saw today they have offered more stock, lets see at what price. I am looking at a better price to get in to todays price of $38, as other poster here highlighted, they don’t have many short therm catalysts. I would be happy to get in but below $30. Also, do you know when is or was the AVXL lock up period expiration after their IPO?
    Also related to GT, are you watching at EDIT and NTLA for the future? I follow both but waiting still to get in at cheaper valuations. (although they are going down quite quick)

  15. …Continuation on AVXS
    Have you looked at this bearish long article? these guys are really bear on AVXS
    Not only because of BIIB-IONS superiority, but also on possible adverse event in one kid would kill the stock price. Also they mention the trial done only in one center (with links to the co) with 15 kids.
    Also is striking to see that in the new secondary, one of the board members is selling stock and “PBM Capital Investments, LLC, the selling stockholder identified in this prospectus…”

  16. Ohad, do you know if BLUE is going after a much smaller segment of the SCD patient population than GBT? Believe I heard that BLUE is going after severe SCD patients and wasn’t sure if GBT was doing the same or if they are going after a much broader population with their oral drug. Just curious about truly how much of a competitor BLUE is to GBT or if GBT drug may still have a role in spite of BLUE success with their gene therapy treatment.

  17. Ohad
    You wrote in the past that one of the (many) reasons to like RGNX is their MPS I and MPS II programs, which are still in pre-clinical stage.
    If you follow SGMO, how they compare to their MPS programs – already in Ph 1/2. SGMO is also using AAV vector, 2/8 though.

  18. Hi Ohad,

    Do you have an updated price target for EXEL? What are your plans for your holdings based on your outlook for pivotal events like a potential firstline RCC expansion and the HCC indication?

  19. Thanks for your wonderful post again, Ohad. REGENXBIO’s current licensing to 9 GT players seems quite strong for AAV9, a big platform company.

    With $SAGE, in the chance that should STATUS fail, do you think there’s enough value in PPD alone to develop 547? Have been reading the short report and rebuttals but thinking about bear case.

  20. Hi Ohad,
    Re: GILD -PARP inhibitors
    Which one do you like better? TSRO vs. CLVS
    Apart from co. management of course.
    Gene H.

  21. Ohad, can you explain why the recent redemption of $EXEL dept via shares is not reflected in an increase of total # of shares outstanding (which remains at 230m outstanding -should this be in the range of 285+ shares outstanding)? What does “not fully dilutive” mean in this regard? Where are those converted shares? Also, assuming stellar CaboSun results in October, what is the upside to SP?

  22. $EXEL People think it has a higher probability to pass on the 2nd interim, and did not pass the 1st one due to small alpha spend, too high a standard. What is your take on that thought ?

  23. AGTC down substantially today. You mentioned AGTC in regards to Spark. Any updated thoughts?

    Thanks for all your contributions…

  24. $ESPR What do you think of Esperion at the moment for a new buyer ? It seems to be fluctuating up and down.

  25. Ohad, $EXEL receives $60 millstone for EMEA approval RCC. Majority of debt paid off, CABOSUN data may be strong, Q3 looking to be another surprise, why not build towards a Q4 aquistion?

  26. >>AERI – haven’t been following for a while
    AERI Announces Statistically Significant Data from Roclatan Phase 3 Mercury 1 Trial , do you consider buying now

  27. $EXEL SP is on fire. Late abstract for Cabosun oral presentation at ESMO and momentum trading should propel it forward until the day after ESMO or even till earnings report. Your negative sentiment on HCC 1st interim seems off, given that no one really expected it to clear the high p hurdle intentionally set. My Q is why no drug rights deal for Japan? If waiting on HCC why not agree on contingencies. Seems like there are other discussions going on. Do you still advance the notion that no b.o. will occur until more clarity on RCC sales, HCC topline and Cabosun frontline?

  28. Hello Ohad,

    Thank you for taking the time to write this excellent piece. I know you are not covering this stock right now but have you taken a look at MEIP (MEI Pharma), Their frontline drug candidate Pracinostat was granted by the FDA “Breakthrough Therapy Designation” in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy. Furthermore, they received an exclusive license, development and commercialization agreement with Helsinn, a Swiss pharmaceutical corporation, for Pracinostat in AML. They received near-term payments of $20 million, including a $15 million upfront payment and a $5 million payment upon the earlier to occur of (i) dosing of the first patient in the upcoming Phase III study of Pracinostat in newly diagnosed AML patients unfit to receive induction therapy, or (ii) March 1, 2017.

    I would love to hear your opinion on their phase 2 trial as well as their chances of approval for phase 3. I get this feeling that this stock in heavily undervalued.

    Thank you

  29. Chubi,

    I agree with you that MEIP is very undervalued. One thing that you didn’t mention is that Helsinn is going to financially support a trial with Pracinostat in high-risk MDS to be run by MEIP.

    The argument against the results of the Phase II that it was not a controlled trial doesn’t hold much water, IMO. Everyone knows exactly what Vidaza can and does do: approximately a 10.6 month survival for elderly AML patients. Pracinostat’s 19.1 month OS in the same patient population is very impressive. (Some analysts thought that if Pracinstat showed a 12 month OS, it could get approved.)

    MEIP’s enterprise value after the deal with Helsinn is still less than zero. (DewDiligence thinks that this has to do with MEIP’s sorry history.)

    Final results are not due until 2018. I suppose it’s quite possible that the treatment landscape in elderly AML patients could have changed by then. That would be my major concern.

  30. Hey Richard,

    Thanks for the reply it is much appreciated. I am perplexed that you think the final results will not be due until 2018. Given the breakthrough therapy designation by the FDA I would assume that Phase 3 would completed much earlier. Unfortunately, the history of MEIP’s trials have had a negative impact on the current stock performance. However, when we take a closer look at the shares traded, it would seem that the majority of the decline can be attributed to one player here:” Vivo Capital”. They still own a substantial amount of shares but the impact of their selling on the overall share price should reduce substantially.

    As far as the treatment landscape changing anytime before 2018 I have my doubts about that one but only time will tell. Could you please elaborate on that? What possible changes could occur that would drastically affect MEIP’s pipeline? Are those changes likely given what we know currently?

    I await Richard and Ohad’s reply,

    Thank you

  31. Chubi,

    Agree with you about Vivo Capital. I plan to talk to Pete DeSpain about that.

    The 2018 date comes from Dr. Gold’s last presentation about enrollment and data read-outs.

    Hopefully, Ohad will be able to tell us something about potential new treatment regimens in elderly AML. I don’t know enough to even make a guess.

  32. Hey Ohad
    what about avalanche (foegot what they renamed after merger with anapura). Have you given up on them?
    I know you prefer not to comment on car-t tech; but would love your take on FATE and tgeir programmed cells tech. Tgey have solid partnersips and seem at forefronf. How does their approach in graft vs host disease compare to BLCM?
    Have you looked more closely at VTGN? A heavy hittet from TEVA joined as CSO, and the other scientoc people running the trials seem first class and leadres in their CNS field (ketamine, depression).

  33. Sorry for the late response, I was traveling last week.

    lgonber (ONCE/AVXS) – Agree about valuations not being cheap but if gene Tx is going to be the next big thing in biotech there is plenty of upside. I will try to go as diversified as possible as at this early stage it’s hard to pick the winners. So far the dose AVXS uses looks safe and production shouldn’t be a big issue given the number of pts. Hard to compare doses between different trials and products. AVXS’ next catalysts are introducing P3 trial design and quarterly updates, not huge events but definitely important. I still like EDIT/NTLA but prefer to wait until we get more clarity and approach clinical data.

    Regarding the report you mention, all valid points that should be taken into consideration, this is why diversification is important.

    GBT/BLUE – I don’t think SCD will be cornered by a single drug (two different approaches may be synergistic) but if I had to bet I would put my money on BLUE because the potentially long term implications. Depending on the expression levels they see with the improved Lentiglobin, it makes sense to use it in a more severe population.

    andre (RGNX/SGMO) – Was never a big fan of zinc fingers plus RGNX’s vectors appear more suitable for neurologic diseases. Therefore, I think RGNX has a higher likelihood of success (but every P1 program is obviously very risky).

    Wildbiftek (EXEL) – I admit I didn’t expect the stock to reach 13.5 before ESMO, don’t expect it to move much higher without something new (Japan deal, phenomenal CABOSUN data, intriguing PD1 combo data or of course M&A).

    Garry Xo –
    RGNX – Agree, assuming AAV9 really crosses the BBB.
    SAGE – I think SRSE study will succeed but no guarantees here of course. Yes IMO PPD is an attractive market in itself.

    Gene H. (CLVS/TSRO) – I think TSRO has a more compelling case and a phenomenal P3 data across BRCA+ and HRD+. CLVS’ recent data doesn’t seem to be that different than that of AZ’s olaparib.

    Steve (EXEL) – The number will probably be updated in future filings (not sure if all notes were already converted). Stellar results could push the stock beyond 15$ imo.

    curiousgeorge (EXEL) – I don’t share this opinion and believes that has there been stellar activity the 1st analysis should have demonstrated it.


  34. $ESPR You forgot to answer my ESPR question , what do you think of the P2 success chances ? Also, is it a good buy right now, or would you wait for the P2 results, is it derisked enough now ?

  35. Ohad
    you wrote that RGNX’s vectors are suitable for CNS diseases.
    What do you think about VYGR – they specialize in gene therapy for CNS. Some important catalysis by the end of the year – Ph 1b data of two cohorts.

  36. Gerry (AGTC) – Obviously their update was disappointing and I guess it demonstrates the risk in such a nascent field as well as dealing with these ultra-rare indications. I would still consider them as part of a diversified gene therapy portfolio given the cash and the Biogen funded programs

    curiousgeorge (ESPR) – I still it and think their drug works. Key catalysts are high dose statin add-on (limited upside but significant downside imo) and PCSK9 CV outcome data next year.

    Steve (EXEL) – The stock is behaving better than what I had expected. Data at ESMO (primarily CABOSUN but also PD1 combo) will set the tone until the next Q report. I feel an acquirer would want to wait until mid 2017 too see the launch trajectory but perhaps the lingering Japan deal implies they are discussing M&A as well, who knows…

    Druz (AERI) – That was one nice turnaround, still didn’t have a chance to review the data so no strong opinion there.

    John (MRNS) – Early data was encouraging but as we saw it’s very hard to interpret small open label studies.

    Jay (EXEL) – Yep stock is very strong. I agree the deal in Japan takes longer than expected which might imply they are discussing an acquisition with a Japanese pharma but that’s pure speculation on my behalf. Yes I still think an acquirer would want to see a couple of quarters but hope I am wrong…

    Chubi/Richard (MEIP) – Haven’t looked at them for a while but overall I am not optimistic about their drug which doesn’t appear to be that differentiated from other pan-DAC inhibitors. The BTD in AML is an enigma to me as I didn’t find their data convincing enough. Their P2 randomized MDS study failed after generating a promising signal in a single arm trial so I am somewhat cautious on their AML data.

    Will try to answer the rest of the Qs later today…


  37. Dan (ADVM) – Actually I think that owning a small portion makes sense given their cash position and the differentiated clinical strategy. Their A1AT program, expected to start P1 very soon, looks unique (as well as their intention to use intrapleural and intravenous administration).

    curiousgeorge (ESPR) – It depends on how much risk an investor would like to take. I personally believe the trial will succeed but don’t plan on adding more prior to data release.

    andre (VYGR) – I don’t them well enough but their focus on PD, the biological approach and the mode of administration (directly to the brain) make them less attractive imo.


  38. Hey Ohad
    TBRA up 600% on Allergan buyout!
    all NASH sector uplifted
    PS any opinions on FATE vs BLCM?

  39. $EXEL You see now , this is an MDVN type company. If Takeda is planning to use the 20 billion on Exelixis the share price could be $70 dollars. Japanese acquirer makes a lot of sense since Japanese have prevalent Liver diseases. If you are looking to get into the European and US markets why not buy a company that can give the home base market lion share too. It is less risky that way.

  40. Hi Ohad,

    Plus one on Dan. I asked about your sentiments on NASH before. TBRA news seems pretty significant given their recent trial setbacks. Thoughts on others in the space? Gilead and Novo are too large cap but ICPT or GNFT or others?


  41. Hello Ohad,

    Thank you for the reply. I believe you should take another look at MEIP because their lead candidate drug Pracinostat showed very impressed data from its Phase 2 trial. I believe the company you assessed awhile back is totally different from the company now.

  42. $EXEL CABOSUN moved to presidential session prime time at ESMO! Safe to assume this will be big and propel stock to 20-25 range and BO? Ohad, conservatively what is the company worth /multiple on 1L and 2L RCC alone?

  43. $EXEL, Cabosun data presentation change to the presidential symposium smells like a game changer. RCC treatment algorithms are, and will be, in flux but if Cabo can move to the frontline b4 checkpoint inhibitors this would be a clear coup. I say SP clears $20 if Oct 10 presentation is a home run. Appreciate the banter.

  44. Dan – Amazing, AGN are becoming the new CELG…
    I still like BLCM, FATE not so much.

    curiousgeorge (EXEL) – Agree EXEL is a good fit for Takeda but it’s definitely not a 20B acquisition.

    James Eslea MacDonald (TBRA/ICPT/GNFT) – Agree about the TBRA deal being a significant event that could catalyze the entire NASH market (just saw that AGN bought another NASH company). Don’t have any strong opinions there as I don’t know the field well.

    Chubi (MEIP) – Will take a look.

    Steve (EXEL) – That’s good news, probably they didn’t have enough groundbreaking data so they had to fill a time slot but obviously a positive indication. If cabo gets into 1st line the potential as monotherapy is probably $2B and depending on market share EXEL could be worth 5B, which is around the current valuation.


  45. Hi Ohad

    What do you think about IONS at current levels from a long term perspective and in terms of their Antisense Technology in general?

    Many thanks

  46. Thanks Ohad. Know you prefer long term value and NASH is likely to get very bubbly over the next 2-3 years.

  47. Hi Ohad,

    You say: “I admit I didn’t expect the stock to reach 13.5 before ESMO, don’t expect it to move much higher without something new (Japan deal, phenomenal CABOSUN data, intriguing PD1 combo data or of course M&A)”
    Yes, fair enough. However, there is a very high probability that a Japan deal will be announced soon OR that a Japanese company will acquire EXEL. Also, given what MammaRoche is doing you can safely expect intriguing PD1 combo data . Moreover CABOSUN data should indeed be very solid (or phenomenal).
    No wonder that the stock is at 15$…

    Also you say: “…depending on market share EXEL could be worth 5B, which is around the current valuation”. But EXEL’s market cap is just 3.4B$, a far cry from 5B$. So, if you think that just RCC (first and second line) is worth 5B$, then EXEL’s stock is worth 22$, even without any contribution from cobi (which is actually quite significant) or XL888 and the rest of the pipeline.

  48. Kevin (IONS) – I am not a big fan of antisense in general. Overall a lot of programs and resources that got into this area but clinical results are underwhelming to date with nusinersen as the only exception. IONS’ 4B+ market cap more than captures royalties from this program, not to mention potential threat from gene Tx.

    Peter (EXEL) – Hope you are right and recent strength in the stock may imply a positive surprise at ESMO or a buyout. The market cap that appears finance sites does not include the recent debt conversion.


  49. Ohad,

    Can you elaborate (with some hard data) on: “The market cap that appears finance sites does not include the recent debt conversion.”



  50. $EXEL Cramer says sell: “I probably overstayed my welcome on this thing. We recommend this thing at $3 and $4 and now it’s up to $15, but I really believe that they’ve got the right drugs … If you bought it at $2 or $4 and it’s at $14, take some off the table. Let’s be prudent, OK.”

    He obviously doesn’t feel CABOSUN and 1L RCC is a $1.5-2b opportunity. The writing is on the wall -big Pharma will not pass up a billion dollar bolt on opportunity for a relatively cheap valuation!

  51. Hey Ohad
    thanks for your answers.
    What is your take on ARRY’s results?
    also Implications of positive GLAGOV (Amgen PCSK9) study for ESPR?

  52. Any insight on ARRY results, – Also do you see this ARRY doing better going forward with what they have in hand ?

  53. Frank Marzella (MRNS) – Not aware of any new developments.

    Peter (EXEL) – EXEL is in the process of converting its 2019 debt which should add ~55M shares. See their press release and filing from August.

    Steve (EXEL) – I think he just advises people to take some profits off teh table if they have a 3x return, which make sense to me. I don’t think he bases this on CABOSUN data.

    Dan (ARRY) – Very nice data, will be interesting to see safety profile. While superiority over encorafenib was almost stat significant, they have enough indirect data to suggest their combo is at least as good if not better than Zelboraf+Cotellic.

    GLAGOV data are obviously positive for any LDL-C lowering agent, still need to see CVOT of course….

    Ruhu (ARRY) – Yes,this is a major win. Need to see full data of course but the combination looks very effective and potentially differentiated.

    lgonber (ARRY) – Yes I did….


  54. ARRY up 81.1% in a day: best performance EVER for the stock…

    Given the data, what are we to do? Hold? Sell?

  55. Richard Baker (TCON) – Don’t have a strong opinion there. They did have some intriguing responses with VEGF therapy but data are sparse.

    Peter (ARRY) – Yep, too bad I couldn’t hold for just 3 more weeks….
    Not sure if the 1B market cap is justified given the fact the HR was still similar to competing regimens (although median difference was really impressive).

    Ruhu (ARRY) – Impossible for me to predict and I can say that after selling the stock 3 weeks ago. They will probably need to raise significant funds to support commercialization in the US so there might be a better entry point near term.


  56. Any thoughts on Agenus (AGEN)?
    I took some of my gain on EXEL (thanks in large part to you) and placed it in this, and increased position in CARA.
    Thank you for this excellent blog.

  57. Ohad,

    Regarding ARRY you say: “They will probably need to raise significant funds to support commercialization in the US so there might be a better entry point near term.”

    Voilà, next day and the company indeed announces a 115M$ raise.
    However, Array’s liquidity situation is very strong, particularly considering the funds coming from an imminent Japan deal and from Pierre in 2017 (upon approval in NRAS and BRAF).
    I hence disagree that it needs to raise any more funds and in all honesty also disagree with today’s raise. In fact, the company has more than enough money to go solo in North America, if it so chose (a big “if”)
    Moreover, advancing 797 will be cheap, and cost less than an outlicensing (happening next year) of the compound will bring in.
    Finally, let’s not forget the deal with Astra: plenty of good things (and milestones/royalties) can still come out of it.
    1B$ for all of this is a pittance.

  58. Lawrence –
    AGEN – valuation is hard to justify IMO although the deal with INCY is great.
    Between AGEN and CARA, I prefer CARA which I consider owning as a hedge on TRVN although there are also non-overlapping indications.
    Glad to hear about EXEL.

    Peter (ARRY) – Don’t forget they have a significant debt and building a salesforce isn’t cheap.


  59. ARRY – announced today the pricing of an underwritten public offering of 18,400,000 shares of its common stock at a public offering price of $6.25 per share
    how come the stock didnt decreased to match the offering?

    I just wonder , why all the bio webcast are audio , wouldnt it be much beter to see it in video?


  60. AUPH met all secondary endpoints. Maybe a little premature to disregard its potential. Thanks again for all your work and sharing your thoughts.

  61. Ohad, any opinion on MDGN?

    The Ph1 data in ADHD (mGluR mutation) looks intriguing – proper dose and time response. It looks that they have a solid prove of principle for this genetic biomarker. The safety is good – no SAE. They will report P2/3 top line data in H2.

    The other data expected in H2 – Phase 1/2 in 22q Deletion Syndrome, another orphan drug. No clinical prove so far (except improvement in 2 pts), but the biomarker is the same, so it may work as well.


  62. hello Ohad,

    guselkumab data from Jansen/MorphoSys looks quite impressive.

    I guess given only 5% royalty not reason for you to get back into MorphoSys yet?

    many greetings

  63. ESPR had to release data in Q3. We are in October and no news. What are your thoughts on this delay? thanks

  64. $EXEL M&A in play, CABOSUN data at ESMO, if solid enough for 1L approval and Q3 revenues beat again (60-75m?) then it would be hard for any big pharma /bio to not take a serious look at EXEL?! Add HCC potential (400-500m) Cometriq (400m for the entire molecule), Cotellic potential ($200-500m) and the Daiichi Snakyo p3 potential ($250m?) – these can be paid out as futures milestones. RCC 1L & 2L alone is a 1-1.3 billion $ opportunity conservatively. Multiple of 4-5x peak revenues beings the BO price anywhere between $18-21+ ($5.2-6b) with an additional $1-2 based on milestones in the future. It’s on!

  65. Hey Oahd
    are you attending ESMO?
    what do you think of recent development regarding RCC and CABO.
    Three presidential Symposiums — this is a first. Bodes well for patients and research. What will you be paying close attention to? A lot offocus on PARP showdown. Looks like PFE parp is also very promising.

  66. Alex (ARRY) – Very impressive

    Re EXEL – Natural to see this fluctuations, some of it is driven by news like the initiation of P3 for lenvatinib+PD1 in 1st line RCC.

    jh (AUPH) – Pretty impressive stock move since I sold, still skeptic here

    andre (MDGN) – I still didn’t have a chance to delve deeper but was intrigued with using a bioarker for ADHD (saved Jefferies’ initiation on them but couldn’t find the time).

    gerwei (MRNS) – Hard to interpret the data without a control arm.

    Christian (MOR.DE) – Agree on both. Data are very good but will guselkumab be able to take market share from IL17 mAbs?

    lgonber (ESPR) – Don’t know if it means anything. I decided not to increase my exposure because there is much more to lose and upside is limited imo.

    Steve (EXEL) – CABOSUN data need to be excellent in order to push stock higher imo, the PD1 combo data at ESMO were very interesting imo. I think Q3 rev of 70M is too ambitious. In order to have a $18+ buyout near term the company will need something beyond RCC to support valuation, perhaps HCC optionality which is a long shot.

    Dan (EXEL) – I am not attending ESMO although I wish I were given the PD-1 drama…
    I am anxiously waiting to see CABOSUN tomorrow of course, not sure if it will be registration material but there is a precedent in 2nd line RCC (lenvatinib). TSRO’s PARP data were great imo, too early to conclude re: PFE’s molecule. SGEN had impressive data i bladder cancer.


  67. Hi Ohad,

    What are your thoughts on the Cabo data?

    Based on these results, Exelixis plans to submit a Supplemental New Drug Application (sNDA) for cabozantinib as a treatment of first-line advanced renal cell carcinoma, and is working with the Alliance to transfer the complete CABOSUN clinical database to Exelixis.

  68. Also… TVRN has been in the dumps a long while. sitting at $300M market cap… would you consider adding more? why aren’t investors more interest in the stock?

  69. “CABOSUN data need to be excellent in order to push stock higher imo”
    He! Is that strong enough?! 😉

  70. Dan (EXEL) – Yes results look very good and the fact EXEL plans to file based on discussion with FDA is encouraging. Sutent is losing patent protection soon so the impact on PFE is not that big IMO. Obviously, it doesn’t bode well for Inlyta, which appears underwhelming compared to cabo and nivo.

    longgreeen (EXEL) – See above. Overall very good data in a tough patient population plus the OS signal is promising albeit not stat sig. With lenvatinib as a precedent, they have a chance of getting 1st line approval but FDA can also be unpredictable…

    Dan (TRVN) – I still like them and plan to add more early next year. I believe their P2 data set although they are still a high risk bet.

    Peter (EXEL) – It’s obviously strong but apparently not strong enough to push the stock to 15….

  71. Garry Xo (EXEL) – They said they plan on filing a sNDA based on CABOSUN.

    Guilty (STML) – Actually, now that CD123 bsAbs are experiencing challenges (MGNX need to work hard on dosing schedule and it doesn’t sound like they are seeing stellar efficacy), I feel more comfortable around STML. An interesting idea ahead of ASH.

    Terry – I like BPMC a lot but as you stated valuation is too high for me. Re: CASC, clinical data haven’t that great imo.


  72. Bouschka (ESPR) – Looks good, need to listen to their webcast. Basically, they removed a major overhang regarding the utility and interchangeability of ETC-1002 with high dose statins. The placebo arm had a relatively high LDL-C increase but I don’t think it’s unprecedented.


  73. Thanks Ohad ! I also noticed todays collaboration between REGN and OCUL. Is this a vote of no confidence in ADVM or just a covering of all alternatives ?

  74. ESPR selloff after good news released. Trading so cheap at the moment. Any explanation or opinion? sometimes is difficult to understand the market.
    Do you have any opinion on ADXS?
    thank you

  75. Your comments on EXEL almost a year ago were right on. Word for word… You have a new follower for sure. Do you recomend it as a buy today!?

  76. Bouschka (REGN/OCUL/ADVM) – I would say it’s somewhere in between. Even if wet AMD becomes amenable to gene therapy this is a long term solution and so far the technology used by ADVM and other companies is probably not good enough. The REGN/ADVM collaboration is on rare retinal diseases from what I recall. I view this is a short term solution that can help protect eyelea from Avastin and Lucentis biosimilars.

    Alex (GLYC) – Sorry don’t know them.

    lgonber (ESPR) – I also think it’s cheap. The data were not a home run but a major de-risking event. Next catalyst is PCSK9 outcomes data which is still 3-6 months away.
    Don’t know ADXS well.

    Kevin (TTPH/IMGN) – Don’t have a strong opinion on those names. The recent data from SGEN in bladder cancer made me more optimistic about ADCs in general and IMGN clearly has a validated technology.

    Stefan Mauer (SGEN) – Hard to say. BB have a huge position, don’t know what the plan is….

    jose miranda (EXEL) – Thanks! I prefer not to recommend specific stocks for a specific investor as each one of us has a different investment profile. I personally intend to hold EXEL as the risk is quite low imo and upside is still there (buyout, Japan deal, more visibility for the PD-1 combos for cabo or cobi etc.). I still plan to sell a portion of shares in the virtual portfolio simply because the position is dysproportionally large.

    Peter (EXEL) – I assign a 20-25% likelihood of success in HCC

    Jack (ABEO) – Hope the data are good although it is still unclear what exactly will be reported and how they can prove they reach the CNS…


  77. Hi Ohad,

    “Peter (EXEL) – I assign a 20-25% likelihood of success in HCC”
    That is too low, given the data to date (in all indications), imo.
    I’d say 50-55%

  78. Is ABEO ok to buy at current stock price? Do you see pullback and might have better entry point in future?

    Any other company competing for the same diseases, and how far ahead are they with it.

    Which is the best gene therapy stock, you have in your portfolio – that you see has good potential

    Thanks always for your inputs

  79. Any thoughts on xencor? Saw you were negative on mgnx cd123. Do you like loxo at the current valuation? Any thoughts on adding xlrn to the portfolio? Thanks

  80. 677727 198724It is a shame you dont have a donate button! Id without a doubt donate to this brilliant weblog! I suppose for now ill settle for book-marking and adding your RSS feed to my Google account. I appear forward to fresh updates and will share this weblog with my Facebook group. Chat soon! 836014

  81. Bispecific antibodies – in the past there were many questions about companies advancing these therapies like MGNX and XNCR. Is there any specific reason you stay away from these field?
    Talking about bispecifics, any thoughts about MRUS? They have two readouts by the end of the year.

  82. hello Ohad

    isnt BDSI too cheap at 135 mio market cap?

    where do you see greatest risks?


  83. Ohad

    Dnai is trading at a 50m mkt cap.they have 120 million in cash,no debt.can you explain in general why a biotech would be trading at such a discount to their cash holdings,or if your familiar with the company and can share some thoughts.

  84. Hello Ohad
    what is the rationale for selling part of arql and fmi?
    what are their catalysts?

  85. Hello Ohad
    what do you think of trvn? it’s in a decline trend..
    what do you think about selling before the election?, seems either way bio will be hit

  86. JuliaVeganLove – Sorry, prefer not to comment on CAR/TCR companies.

    Peter (EXEL) – P2 2 data were very impressive but if cabo generated a similar level of efficacy in P3, the trial should have been stopped by now imo.

    Ruhu (ABEO) – Hard to predict stock fluctuations. I view it as a long term position especially after last week’s results which were very encouraging imo.
    Regarding competition – There is not a lot of competition in Sanfilippo A. Lysogene expects to start a P2/3 using a different viral vector (AAVrh10) that has to be injected directly to the brain. Shire has an enzyme replacement therapy program with intra-thecal administration but status is unclear.
    The closest competitor is Esteve (also uses AAV9) which expects to be in the clinic soon :

    Sanfilippo B is more crowded – ALXN has an ERT program from GEVA (given IV), BMRN has another ERT that needs to be injected to the brain (via reservoir), QURE has an AAV5 program that needs to be injected directly to the brain. ALXN and QURE demonstrated encouraging data but are not a single IV administration like ABO-201.

    Hard to pick a single gene therapy stock. In such a risky and early stage field I prefer owning a basket.

    Mike –
    XNCR – NVS deal was impressive imo but I am still pessimistic about bsAbs until more clinical data emerges.
    LOXO – I still like them but valuation is not attractive enough imo.
    XLRN – I like the MDS program (not threatened by gene therapy) but the RCC program isn’t attractive imo and valuation is too high imo.
    PIRS – Still not convinced anticalins are superior to antibodies.

    Andre – I was originally very optimistic about bsAbs but so far clinical data have been underwhelming without a single success story except Blincyto. Therefore I am cautious about all bispecific platforms although many are robust engineeringing-wise.

    Christian (BDSI) – Sorry don’t know them well.

    Dave (DNAI) – When a stock is traded under cash it means the market assigns a negative value to the pipeline (leads to cash burn without any real hope for positive data). Chk1 and Cdc7 have already been explored without much success so skepticism is understandable.

    Alex –
    ARQL – I am not optimistic about the HCC data so decided to decrease exposure. Still like the other programs.
    FMI – Market penetration has been slower than expected (as well as reimbursement)
    TRVN – I still like the company and plans to add more early next year. No idea about how elections will impact the stock or the general markets.


  87. Ohad -why havent $exel started new trials? Been over 1.8 years since RCC top line results? They have raised $260 from ipsen, could have parterned with Japanese co; yet the chose to pay down debt and conserve cash?! All signs point to preparing for buyout or negotiating BO deal? Please comment. Also could Q3 earnings surprise $60-70m range trigger deal ?

  88. Hi Ohad,

    You say: “P2 2 data were very impressive but if cabo generated a similar level of efficacy in P3, the trial should have been stopped by now imo.”

    Precisely. P3 data does NOT have to be as strong as P2 ones to gain approval.
    It just needs to be strong enough… Not stopping the trial early is the rule, even for later to be approvel compounds. Stopping early was never in the cads, and would have been very surprising, imo.

  89. Ohad said: “PIRS – Still not convinced anticalins are superior to antibodies. ”

    Wow… quite a statement!
    Anticalins have all of the binding capabilities and therapeutic potential of mAbs, but are smaller, easier to manufacture, far more tunable in kinetics, easier to create bi-specific and tri-specific binding regions, and can be dosed inhaled and potentially even orally.
    There’s really no area where I see mAbs superior, unless you are looking for some sort of in vivo created approach

  90. $EXEL What do you estimate the revenue from Cabometyx, Cometriq for Exelixis in Q3 ?

  91. XENE

    Hi Ohad,

    are you still holding XENE? Do you think its a good buy here in front of the results for P1 coming and the platform in general?


  92. Hi Ohad,

    Pfizer just discontinued their PCSK9i bococizumab. With recent positive topline Phase 3 results, how do you think this readout will affect the future of ESPR? I see it as a negative if a major Ph3 player does not have faith in the field —

    Thank you

  93. Hi Ohad,

    TRVN share price has never been Lower. Do you see any reason for this weakness except for market conditions? Do you plan adding in your next portfolio update?

  94. $EXEL What do you think of Exelixis valuation , do u think it makes them a stronger buyout candidate now, they seem to be setting themselves up to be a buyout candidate. What would be your valuation now ?

  95. $EXEL ~286m shares now outstanding, @11.75 =$3.36b market cap. Assume a 55% premium puts the price at $18.2 or $5.2b takeout price. They will end the year with ~$480m in cash and $200m in debt. Assume they add $250m via Japanese partnership plus royalties. They have $1b in write offs; Cottelic revenues negligible in the near/ perhaps long term. All eyes on Cabometyx sales -assume on track to make $200m in the next 12m RCC alone. $40m/y for Cometriq. ~$150m 2016; $250m 2017?; $400m 2018?; $600m 2019?

  96. Avxs

    Do you plan to sell a bunch of shares? MC 2.13B seems a little bit expensive for a company in this stage?


  97. ABEO

    Enterprise value compared to RGNX and AVXS seems a little bit low? Do you have an explanation ? Thanks, Horst

  98. Ohad, thanks for taking your time to write this blog and answer questions.
    Are you, or anyone on here, familiar with a Swedish company called Hansa Medical,
    HMED? Rod

  99. Steve (EXEL) – I think they realized they had to contain costs after starting 3 pivotal programs (prostate, RCC, liver). Don’t forget they have a broad CRADA program with the NIH (CABOSUN was part of this agreement) so there are additional active trials.

    Jack (ABEO) – I think the offering makes sense after the significant move and the need to aggressively pursue MPSIIIA/B following the encouraging data with ABO-102.

    Mike (ArgenX) – Haven’t looked at them for awhile… I remember they had a strong platform but it was hard to find a near term value creating events. The FcRn approach is interesting but will take time to generate data in MG or ITP.

    EXEL – Happy to be wrong here…
    PIRS – The challenge is translating these technical advantages to clinical ones. So far I haven’t seen this.

    curiousgeorge (EXEL) – I was hoping for a slighlty highe sales figure for Cabometyx ($35M) but $31M is clearly a strong launch.

    Horst (XENE) – Yes I am still holding (but growing impatient…). Genentech should have communicated their plans by now for the NaV1.7 program. The acne program is interesting but less lucrative imo. I still like the approach of looking for extreme phenotypes as a way to identify drug targets, was hoping to see more drugs in development by now.

    Garry Xo (ESPR) – I think it is a combination of the disappointing PCSK9 launches and some specific issues related to PFE’s antibody. I still believe ESPR’s has a lot of value as an oral LDL lowering agent and that PCSK9 CVOT will validate the LDL hypothesis.

    Chris (TRVN) – I don’t see any reason for the weakness, yes I plan on adding early next year.

    Kevin (ONCE) – I don’t think it’s a major setback as the liver enzymes were contained with steroids and FIX expression may still continue (need more follow up for that)

    curiousgeorge (EXEL) – I think they are close to be fairly priced based on 2nd/3rd line RCC. There is still upside from label expansion (PD1 combo data in bladder was attractive imo) but I don’t see the stock go beyond $15 soon.

    Steve (EXEL) – I think the sales trajectory makes sense (especially if they get 1st line approval).

    Horst (AVXS) – I don’t plan to sell shares despite the high MC, especially given the very favorable feedback from the FDA. SMA1 is quite rare but other SMA types may increase opportunity to $2B long term so valuation may be justified if data continue to hold,

    ABEO – I think they still don’t get credit as a “professional” pure play gene therapy play. Agree there is a valuation gap especially if we count the MPSIIIB in.

    Rod Gex – Sorry don’t know them.


  100. Stock promoters responsible for numerous biotech wipeouts run this “company,” while ABEO temporarily trades near the highest market capitalization in its 20-year history.ABEO’s auditor Whitley Penn cited by PCAOB repeatedly for “audit deficiencies”. This is the same tiny auditor who oversaw the alleged UDF “Ponzi scheme” exposed by Kyle Bass.Insiders have collected a shocking ~$35m in compensation, which exceeds 50% of ABEO’s R&D spending since 1996, while losing over $325m of shareholder cash, and yet accomplishing apparently nothing.ABEO insiders have accumulated multi-decade track records of shareholder wreckage including several prior companies that went to essentially zero.ABEO is set to decline 92% as its science fails and the stock promotion comes unwound, just like other Steven Rouhandeh biotech stocks.ABEO appears to be a bottomless pit of self-enrichment for the long-time stock promoters who run this “company” ABEO’s science is completely unviable, calling into question the very reason for the company’s existence. ABEO’s 20 Year History: Crummy Reverse Merger Penny Stock with Ties to Insiders Convicted of Fraud. Abeona is essentially a failed rollup of Blech and Rouhandeh investments that each collapsed. Abeona is the end product of a more than 20-year history of failure and shareholder value destruction that has ties directly to a convicted felon who served jail time for biotech securities fraud.
    An in depth review of Rouhandeh’s past involvements revealed an alarming pattern of repeated shareholder value destruction. Abeona has been nothing short of remarkable as what appears to be a bottomless pit of cash burn and value destruction. Abeona has lost over $325 million since 2006 and the cash burn has accelerated in recent years Millions of dollars have been shuffled into the hands of ABEO insiders and their affiliates Why is Abeona paying its largest shareholder millions of dollars for investor relations? We looked back and could not find a single important scientific discovery in the entire history of Abeona Estimated ABEO insider compensation has exceeded $34 million. ABEO stock is tantamount to simply giving your money to insiders: You get the dilution, they keep the cash. ABEO’s Auditor Currently Entangled in “Ponzi-Like Scheme” Allegations. ABEO’s auditor issued 8 “unqualified going concern” opinions from 2006 to present.

  101. Hello, its pleasant piece of writing about media
    print, we all be familiar with media is a wonderful source of information.

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