Biotech portfolio updates – Exelixis, Spark, buying more gene therapy stocks

Exelixis – Decreasing exposure on valuation

Exelixis (EXEL) continues to look very strong after hitting a 15-year high on Friday, which is never a bad point in time to realize some gains. While I still view Cabometyx as the most effective agent ever approved in renal cancer (even better than Opdivo), a valuation of $5.1B seems to fully capture the current label.

Exelixis definitely has potential to grow with multiple data readouts for cabo (P3 in liver cancer, combination data with checkpoint inhibitors in GU cancers) and Roche-partnered Cotellic (expected to be in three pivotal trials next year) in 2017. On the regulatory front, the company plans to submit data from the CABOSUN study in 1st line RCC with the potential to get approval by late 2017, earlier than the expected Opdivo/Yervoy filing (assuming positive results).

The company also faces risks. To begin with, the commercial launch looks strong but still hard to predict market dynamics in 2017. Competition from PD1-based combination regimens may make 1st line more competitive, even if Cabometyx receives approval. Another risk lies in the fact that the PFS data from CABOSUN were made based on investigator assessments and therefore need to be confirmed by a blinded central reviewer, which may impact the data the FDA receives.

On a personal level, I cannot ignore my bad track record with other oncology launches (especially Genmab and Pharmacyclics) where I sold too early but the strongest argument for selling one of my two Exelixis position is its disproportional share (~30%) of the total portfolio.

Spark – ASH data set isn’t perfect but still impressive

Spark (ONCE) and its partner Pfizer (PFE) presented updated data for their hemophilia B program SPK-9001. Data continue to show durable, strong production of FIX and a sharp decrease in bleeding episodes but this time with some hiccups: Of the nine treated patients, two experienced an immune reaction against the viral vector (one case had already been reported by the company). Although the immune flares were successfully contained with steroids, one patient had a dramatic reduction of FIX levels from ~48% to 12%, which is considered the minimally required levels to achieve a significant clinical benefit. The other patient was treated with steroids more quickly and had a minor drop from 68% to 65%. Importantly, neither of the patients experienced any bleeding events.

spk9001

The two cases understandably raise concerns but do not impact SPK-9001’s value proposition. Even if the patient who had a sharp decrease in FIX levels is considered a treatment failure (which isn’t the case because there is still clinically-relevant FIX production) a success rate of  89% (8 of 9 patients) is still remarkable. The biggest risk for SPK-9001 remains a life-threatening safety event (uncontrolled immune reaction or carcinogenicity) rather than an imperfect efficacy scorecard.

Alnylam (ALNY) presented data for fitusiran, a siRNA targeting antithrombin for Hemophilia A and B. The drug also led to a robust, dose dependent reduction in bleeding incidence. Of the ten patients who received a higher dose of fitusiran, seven were bleeding-free at the time of analysis.

alny-fitusiran

Fitusiram has a very different clinical profile compared to gene therapies such as SPK-9001. It affects thrombin levels directly so it is effective in both hemophilia A and B which have to be addressed by two different gene therapies. It needs to be administered monthly versus a one-time administration with gene therapy, which is less convenient but also advantageous given the lack of long term safety information for gene therapies. Lastly, although siRNA drugs have a checkered history regarding immune reactions, fitusiran may present a different safety profile without the risk of anti-viral reactions or anti-FIX antibodies (inhibitors).

In summary, while gene therapy represents a more logical straightforward approach for a genetic disease like hemophilia, fitusiran may be able to garner a significant market share especially in younger patients or patients with high inhibitor levels.

Increasing exposure to gene therapy

As followers of this blog know, I am a big fan of gene therapy given its disruptive potential and recent technological advances. Acknowledging the high inherent risk in such a nascent field, I intend to increase my exposure to gene therapy by creating a basket of stocks in order to have a diversified exposure across technologies and indications.

After starting with the clinical leaders: Spark, Avexis (AVXS), Abeona (ABEO) and REGENXBIO (RGNX), it is time to move to the earlier-stage, less validated players. Of these, my favorites are Audentes (BOLD), Dimension Therapeutics (DMTX), and Adverum (ADVM). The market is understandably less excited about these names, evidenced by the relatively low valuations (compared to the $1.5B market caps for Spark and Avexis), but all three have strong platforms and are covering a broad array of indications. Importantly, all three have sufficient cash to generate at least preliminary clinical data.

Audentes is still a preclinical company but expects to have three programs in the clinic in the coming months. The company has a diversified and differentiated pipeline covering a rare muscle condition (X-Linked Myotubular Myopathy), an ultra-rare metabolic condition (Crigler-Najjar Type 1) and Pompe disease which is currently treated with enzyme-replacement therapies.

bold-pipeline

Dimension has a platform of liver-targeted gene therapies (licensed from REGENXBIO) with a Hemophilia B program in P1 and a preclinical Hemophilia A program partnered with Bayer. The company expects to report initial results IN Hemophilia B next month and to advance another program (Ornithine transcarbamylase deficiency) to the clinic imminently. The company has a $105M market cap which is almost entirely covered in cash (~93.8M as of last quarter).

dmtx-pipeline

Adverum was created after Avalanche merged with Annapurna Therapeutics. The combined company kept Avalanche’s ophthalmic pipeline (including a partnership with Regeneron) and added Annapurna’s pipeline which includes programs for the lung disease Alpha1-antitrypsin (A1AT) deficiency and hereditary angioedema. Although the company does not expect to have anything in the clinic until Q4:17, it has a significant $231M cash position, almost double its $119M valuation.

advm-pipeline

Portfolio updates

As discussed above, I am selling one of my Exelixis positions and initiating positions in Audentes, Dimension and Adverum. Gene therapy companies now comprise ~15% of the portfolio, and I expect their weight to increase to ~20% in 2017.

Portfolio holdings – Dec 4th, 2016

biotech-portfolio-4-12-2016-after-changesbiotech-etfs-4-12-2016

136 thoughts on “Biotech portfolio updates – Exelixis, Spark, buying more gene therapy stocks

  1. Hi Ohad
    you intended to buy more TRVN.. why decided not to?
    XENE STML what do you think on adding?

    Thanks

  2. Hi Ohad,

    Thanks for your thoughts. Regarding Gene therapy players what are your thoughts on valuation? For example BOLD is a 370M Marketcap though the EV is much smaller ~ 110M. DMTX and QURE have small EV values = ~10M but QURE has a partner with fairly lucrative terms whereas DMTX is partnered in HemA. DMTX has also guided towards achieving a fairly FIX equivalent to what QURE now has.

    What is your understanding of whether ONCE and QURE are competitors? QURE targets AAV5 and ONCE AAV9 and the latter is more prevalent based on literature. Since SPK9001 cant be used for AAV5 vector patients why is there concern that ONCE will compete in that space?

  3. Hi Ohad

    Thanks for the great insight again re gene therapy. Would you still view the valuation of RGNX as attractive after the recent run up?
    Besides that, what do you think about BLCM after the latest news re BPX-501 and their curent valuation?

    Many thanks
    Kevin

  4. Alex –
    TRVN – I still plan on adding moreut prefeto ait to Jan/Feb time frame.
    XENE/STML – I like them as a speculative bet, no plans to add before mid-2017.

    Richard – I admit market caps are tricky since there is established business model for gene therapies. I personally feel comfortable with the earlier low EV companies like DMTX because any clinical signal will have a major impact. Moreover, if gene therapy becomes a dominant area they will become cheap acquisition targets.
    Regarding ONCE VS. QURE – I view them as competitors as at the end of the day what matters is protein expression and clinical benefit regardless of what vectors are used.

    Kevin (RGNX) – Yes, I still like them as a diversified gene therapy ETF who will collect royalties from potentially tens of active programs. Their proprietary pipeline is a free call option.

    The BLCM data look very good, didn’t have a chance to delve into them, though.

    Ohad

  5. Mike – I prefer to sit on the sidelines for now given the early stage and high valuation of gene editing companies.
    Don’t know MDGN well.

    Ohad

  6. Hi
    Ohad

    I know you moved away from ARRY. Stock has been doing good recently. Any thoughts.

    Ruhulla

  7. Hello Ohad
    What is the next catalyst for ESPR?
    ,and what about FMI? is there something in the near future that can move the stock?
    Thanks

  8. Ohad
    good news for the gene therapy field. VYGR reported solid data in Parkinson:
    – dose dependent and durable improvement
    – 2.2 hours increase in on-time at 6 mo, improved to 4.1 hours at 12 mo, so the patients get better in time after single procedure.
    They are looking at relatively fast path to approval – starting pivotal trail in late 2017.
    How do you value this data?

  9. Hi Ohad,

    Have you considered GNFT recently? The stock price is quite depressed but they are targeting NAS >4 patients for their Ph3s to get better resolution. There seems to be increasing interest for them and the valuation seems low ($660MM) for a huge NASH opportunity.

    Thanks,
    Garry

  10. One more -SGMO. Owned by a lot of “smart money”, but price is getting absolutely crushed…any thoughts? Thanks!

  11. Hi Ohad

    What do you think about XNCR in terms of technology and current valuation?

    Many thanks
    Kevin

  12. Kevin
    Ohad responded several time that he is not in favor of bi-specifics, due to “underwhelming clinical data and no success story except Blincyto”.

    You may check this article: http://www.nature.com/articles/nbt1216-12
    Good overview of the bi-specifics technology and some of the players like MGNX, MRUS, AMGN, XNCS

  13. Ruhu (ARRY) – Their BRAF+MEK combo is clearly active and competitive, not sure if it’s differentiated enough to generate significant revenues though.

    Shark (CALA) – Very interesting scientifically but so far data is underwhelming especially the recent RCC data that demonstrates limited to no added value over Afinitor.

    Alex –
    ESPR – Next catalysts are initiation of P3 and PCSK9 CVOT data next year.
    FMI – This was always about obtaining reimbursement but visibility is still low imo.
    Sorry, don’t know ContraFect well.
    XENE/TRVN – I don’t see them as direct competitors due to different target product profiles. TRVN focuses on post-operative pain with short term treatment, XENE’s NaV1.7 may have a much broader potential probably as chronic treatments.

    andre (VYGR) – Indeed, good for them! I was always a little bit hesitant about their approach to inject directly to the brain with a treatment which is not disease modifying. Need to takea a second look.

    Garry Xo (GNFT) – Don’t know the NASH field well. From what I recall their P2 data weren’t that impressive.

    Shark (SGMO) – I am not following them closely as I was always skeptic about zinc fingers. Probably need to wait for CRISPR…

    Kevin (XNCR) – As andre wrote, bispecific antibodies haven’t delivered (yet) as a class so I prefer to focus on treatment modalities with strong clinical proof of concept.

    Ohad

  14. Hey Ohad
    what do you think of the hit pieces by mako on SeekingAlpha, a few weeks ago he went after AVXS, now it’s ABEO–both were down big time on hit pieces. They seem like planned attacks. Have you read through them, any red flags?
    Thanks
    Dan

  15. Matt (ABEO) – I certainly don’t like the checkered history but what matters most is the science (not developed within ABEO) and clinical data which is early but promising. Still high risk but I like the AAV9 approach and intend to keep my position.

    Dan (ABEO/AVXS) – Some of the points are valid (some don’t look that credible imo) but this doesn’t change the thesis around AAV9-based gene therapies.

    Joel (LIFE) – Only read the PR and hard to justify the term “promising” in the title. On the efficacy side there may be a signal in LGMD, FSHD data is all over the place. Hard to interpret without a control arm…
    Safety is also hard to assess based on the PR, they appear to have some infusion reactions and immunogenicity but not sure if these are showstoppers. A 31% discontinuation rate isn’t encouraging either but not sure it can be attributed just to safety (perhaps some patients felt they were not deriving any benefit).

    Ohad

  16. Thanks for the reply regarding LIFE.

    Regarding DMTX I’m very much long with you. It trades at a surprisingly weak valuation considering its vast pipeline. Market waiting for POC data with hem B I assume? I think Dimension could thread the needle between QURE and ONCE efficacy/safety wise and hope the results next month place it in a more competitive position against ONCE vs. QURE is right now (mgmt has a target of 10% FIX expression with very good safety)

  17. Hey Ohad
    thanks for the reply!

    There are two Israeli companies that have attracted my attention, and I wonder if by chance you know them:
    CANF
    and RDHL which has just released positive pilot results for their antibiotic triplet (RHB-104) in MS and looks like an asset they might partner pretty soon.
    Any opinions?

    Thanks
    Dan

  18. Fyi CitronResearch has a price target of $9 on AVXS. These guys are legit, e.g. were all over Valeant way back when. I did not listen to them way back when on something I owned and regretted it deeply later.

    Quote: Once a competing cure gets FDA approval and looks like it will (Nusinersen) how will AveXis EVER morally and ethically get another patient to enroll in an experimental study.

    THIS CANNOT BE ANSWERED BY ANYONE

    Citron challenges any supporter to a public debate on this topic.

  19. hey Ohad

    what do you think of the new info/releases by GNCA?
    They are moving ATLAS into i/o with some additional partnerships. Do you think this warrants another look? it seems their platform is quite valuable for personalized/targeted medicine, including diagnostics. Following on your initial investment thesis for FMI, it seems to me there is a lot of potential in ATLAS.

    Thanks

    Dan

  20. Hello Ohad…… I would be very interested in your current opinion of Celldex {CLDX} I know the company was a past holding and wonder if the pipeline,science,and management might be good enough for you to purchase once again !??

  21. Shark,

    Quote: Once a competing cure gets FDA approval and looks like it will (Nusinersen) how will AveXis EVER morally and ethically get another patient to enroll in an experimental study.

    1st, Nusinersen isn’t a cure. 2nd, the idea no one can enroll patients into clinical trials once an effective competing drug gets approved is simply not supported by past experiences in ultra orphan diseases space. Look at ERTs for LSDs as examples.

    Citron mostly copied Mako’s report on AVXS – another one on ABEO. They have some valid points in their arguments against these two companies, but some of their arguments are simply nothing, including the one you quoted.

    By the way, they were wrong before. Look up Questcor.

  22. Hi, ohad

    thanks for this informative blog

    Regarding DMTX hem B data in Jan 2017 what do you expect, POC? Why they postphone the data?The low dose can not get the 10% FIX expression? Thanks.

  23. Hi Ohad,

    With FOURIER coming up in 1H17, are you interested in other LDL-C lowering modalities other than ESPR (such as MDCO’s RNAi)? MDCO seems to primary advantages in dosing / pricing (estimated ~$5k less than PCSK9 antibodies), and has similar efficacies to the PCSK9 mAbs.

    In the face of Alnylam’s Revusiran mortality and ARWR’s primate deaths, there is a lot of fear baked into RNAi, but can you see opportunity in the LDL-C context that is being overlooked? Many thanks.

  24. Hi Ohad – have you ever heard of NKTR and their PEGylation platform? I was wondering if you had any thoughts of the company/their science.

  25. Dan – Sorry, don’t know them well

    Shark (AVXS) – Enrolling patients while another drug is approved is indeed an open question but I still believe enough parents will prefer to start with a singe IV administration given AVXS’s data (which are promising but may or may not be corroborated).

    Dan

    Dan (GNCA) – Agree about the potential of identifying immune-dominant neoantigens. ATLAS sounds very intriguing but I am not sure how it compares to other engines. Definitely worth following.

    Bouschka (CLDX) – I prefer to stay on the sidelines for now. The CD27 program has the biggest potential imo although the monotherapy data were underwhelming. They should have combo data with PD-1 next year.

    JQ (AVXS) – Thanks. A plausible scenario in some patients is getting gene therapy early and continue with nusinersen. For others, if AVXS-101 can replicate the P1 data, the long term benefit will be so profound that there won’t be a reason to use a different treatment.

    Bouschka (Evotec) – Sorry don’t know them well.

    andre (FPRX/IPH) – Of the two I prefer FPRX, not optimistic about IPH’s KIR program.

    Ken (DMTX) – A ~10% FIX level is what the company was hinting but this is just validation for their platform and an important read-across to their other liver-targeted gene Tx programs.

    Garry Xo (ESPR/MDCO) – siRNA for PCSK9 could be advantageous to antibodies if it has less frequent administration but as you mentioned there is still a safety overhang with siRNA drugs. In an indication like hypercholesterolemia safety bar is set very high so concerns are justfied imo.

    Al (NKTR) – It’s been a while since I looked at their data but at the time I wasn’t impressed.

    Ohad

  26. Hi Ohad
    ARQL – the HCC trail is the most advanced in its pipeline,results expected summer 17, you dont think it will succeed.. so why hold it now? and not sell and get buck after the trail, or sell and get beak say 2 montes before expected results? noting in the near future seems to drive the stock higher..

    CNAT – would you get back to it after the Novartis deal?

    Thanks!

  27. OHAD….. Just read a VERY interesting article on combo drugs to fight Breast Cancer ! This was on the Science Daily Website. Cabozantinib and Raloxifene were mentioned as a particularly effective combo.Would be interested in your take on the article.

  28. Ohad
    INCY is investing in bi-specifics – nice investment in MRUS. Is their Biclonics platform atractive?

  29. IMGN

    ADCs still a valuable area. IMGN has many partnerships with big pharma and validated platform. EV is about 40m.

    Thus valuation of SGEN is about 60-80 x of IMGN’s. Imo market is overreacting about two decisions in the past.

    Do you agree?

  30. Alex (ARQL) – If there is one thing I learned is that timing stock catalysts is very tricky. While I expect teh HCC study to fail, there may be other catalysts with 092 or 087 that could drive the stock.

    CNAT -The deal is very attractive imo given the somewhat inconsistent data. I don’t plan on getting back in for now.

    Bouschka (EXEL) – Interesting work but very early and not validated in humans, don’t think it will have an impact on the stock.

    andre (INCY/MRUS) – I think the deal with phenomenal for MRUS, very lucrative and transformative. I am sure their platform is attractive and robust but there is little we can infer on the future of bispecifics in general, which to date haven’t lived up to expectations.

    Seppbio (IMGN) – Agree about teh marketing assigning zero valuation to their pipeline which could eventually surprise. Tempting…

    Ohad

  31. PGNX

    Thanks for your reply above. Another name is progenics which is going to release important data for its drug azedra in q1 2017. You have an opinion there? The company still – after the recent run up – seems cheap to me .

    Thank you

  32. Ohad
    next set-back for ADCs. Multiple clinical holds of SGEN programs may complicates the ADC “revival”. It’s unfortunate since the signals in AML were promicing :(
    Do you see anythng else promicing in their portfolio left after they may have to give up on the CD33A programs.

  33. According to ARQL in April, HCC results were expected by year end 2016.

    Alex, where do you see that results are expected summer 2017?

    Ohad, can anything be inferred from the lack of results at this juncture?

    Thanks.

    (original post with link from ARQL would not post, “awaiting moderation”, so re-posting w/o link)

  34. from clinicaltrials.gov

    Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma Who Have Been Treated With One Prior Therapy (METIV-HCC

    Enrollment: 368
    Study Start Date: December 2012
    Estimated Study Completion Date: June 2017
    Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

  35. Thanks Alex. From April 2016 Tivantinib Overview powerpoint presentation last page:

    Interim Analysis
     Triggered with ~ 154 OS events
     DMC was to review and determine:
    • Efficacy stop
    • Continue trial
    • No planned futility stop
     Minimal alpha spend
     Analysis occurred March 2016
    • Trial to run to completion
    Expect METIV-HCC trial to complete by year-end 2016

    Ohad, hopefully you can enlighten us?

  36. Happy holidays, Ohad. You mentioned EXEL will, based on little information given from the 50℅ analysis for HCC, will probably fail in the 75℅ data mark. I think the stock will fall $2-3 if so. Do you think if this were to occur, it would be a good time to get back in for their other programs? Seems to be an attractive takeout target after cleaning up debt.

  37. Hi Ohad
    There’s a great discussion on seeking alpha about HALO’s Phase 2 Pancreatic Cancer Trial whether it’s positive or not. What is your opinion about HALO and their trails/pipeline?

  38. Hey Ohad

    best wishes for 2017!

    Do you think the low valuation makes IMGN attractive? I have restarted a positing in the past two weeks, mostly because of the low valuation and broad pipeline.
    What’s your take?

    Thanks
    Dan

  39. $EXEL Cabozantinib and Raloxifene work well and Raloxifene is cheap so i think if they start a P1 trial and it shows great efficacy in humans which is likely given the efficacy shown in mouse and at a lower dose of Cabo by 25 times it can be a blockbuster.

  40. Seppbio (PGNX) – Sorry, not following them anymore.

    andre (SGEN) – Not sure SGN33A is done as there may be settings in which this agent will be more tolerable. They also have two bladder cancer programs (with Astellas) with good efficacy which could become meaningful down the road.

    Richard Baker (TRVN) – Yes, I still plan on adding ahead of the P3 readout. No opinion on ITEK…

    Shark (ARQL) – I don’t think timing of data means anything at this stage. Last time I checked results are expected Q1 2017.

    Garry Xo (EXEL) – Agree about cabo being one of few available commercial stage oncology assets, which is why I kept a significant position. I also agree about your prediction for a 2-3$ drop but stock still isn’t cheap imo.

    Stefan (HALO) – Don’t know them well, last time I checked results were iffy but have looked at them recently.

    Dan (IMGN) – Thanks! Agree it’s tempting as a wild card…

    curiousgeorge (EXEL) – Again, I would be careful interpreting early preclinical data…

    Have a reat year, everybody!
    Ohad

  41. Happy new year Ohad,

    SGEN – It looks like the issue w/ SGEN’s CD33 ADC is liver toxicity, and this is similar to what we saw with Gemtuzumab Ozogamicin (Myologarg) which also had a DNA crosslinking payload.

    We’ll see if this is an issue w/ IMGN779 which targets CD33 with a DGN payload; it seems they took pains to address the issue of liver toxicity here and the result they achieved is paradoxical given that cleavable linkers are less tolerable in conjugation with maytansinoids:

    “. Treatment with the imine-sulfonated form of
    ADC 3b, with a noncleavable linker, at a dose of 10 mg/kg caused
    a considerable spike in liver enzymes [17- and 35-fold increase in
    aspartate aminotransferase (AST) and alanine aminotransferase
    (ALT), respectively] and an 8-fold decrease in platelet count. In
    contrast, treatment with the ADC 5b with the cleavable linker at a
    4-fold higher dose (40 mg/kg) caused only mild hematologic
    toxicity with a small decrease (2- to 4-fold) in platelets, neutrophils,
    and lymphocytes, and no effects on liver enzyme levels.
    Animals were observed for 90 days and the body weights of mice
    treated with 18 and 40 mg/kg doses both tracked with control
    animals (Fig. 5D).”

    ” Notably, the ADC with the
    disulfide linker tested here was also better tolerated, with a 3.5-
    fold greater MTD in mice than that with the ADC with a noncleavable
    linker. These results indicate that, in the ADCs described
    here, the bystander killing feature provides increased antitumor
    activity but not increased systemic toxicity. Interestingly, this
    finding is counterintuitive, since ADCs of tubulin-interacting
    agents, maytansinoids or auristatins, with cleavable linkers
    (disulfide or peptidase-labile) are reported to be less tolerable
    in mice, compared with those prepared with noncleavable linkers
    (34, 35). Further studies on the in vivo catabolism and distribution
    of these ADCs are ongoing and may provide some insight into the
    cause of the improved tolerability of the ADC with the cleavable
    linker.”

    http://mct.aacrjournals.org/content/molcanther/early/2016/07/13/1535-7163.MCT-16-0184.full.pdf

    The 779 trial isn’t expected to readout for a while, but these details are an interesting wrinkle.

  42. CTMX

    Nice technology and a bit “more cheap” right now. 2017 could be a nice year. Do you like it at current levels?

  43. Hi Ohad

    When it comes to gene therapy and CNS: what made you to not invest into VYGR yet?

    Many thanks
    Kevin

  44. Wildbiftek (SGEN/IMGN) – Thanks!
    I personally don’t feel I have the full picture as far as SGN33A’s safety profile based on the press release. Remember that as monotherapy and in combination with HMAs, toxicity was milder so still hard to say what the ADC’s contribution was given that veno-occlusive disease is a known complication of stem cell transplant.
    Tox findings with IMGN779 are indeed very intriguing, the cleaveable linker seems to play a role (payload is also differentiated) but we also know that so far ADCs with cleavable linkers haven’t delivered great clinical data so far. Reminds me of the EGFR ADC devoid of skin tox in preclinical that had to be terminated eventually…

    Mike – Thanks, unfortunately I don’t know this program well.

    Biosepp (CTMX) – I agree it’s a nice technology with disruptive potential (can deal with a lot of safety hurdles seen with ADCs and IO agents. I still think valuation is too high without any clinical validation.

    Kevin (VYGR) – I am still on the sidelines because they have to inject directly to the brain, PD may have other alternatives and the treatment does not address the underlying driver of the disease like in other gene Tx settings (re-introduction of a dysfunctional gene).

    Seppbio (MGNX) – I still think it’s too expensive although I thought their R&D day was great, especially some of the earlier programs.

    Kevin (RGNX) – It depends a lot on extent and duration of benefit… definitely if one extrapolates from nusinersen’s data and pricing, there is a multi-billion dollar opportunity across SMA types.

    Ohad

  45. Hi Ohad

    Have you come across CLRB and their phospholipid drug conjugates (PDC) platform? Claim to be superior to ADC.

    Many thanks
    Kevin

  46. IMGN: I think you’re talking about IMGN289? It vanished from view after quarterly cc with a quote about it being put back into development after an unexpected safety issue; a pretty big disappointment I agree. That ADC was armed with DM1 though, so its linker wasn’t cleavable:

    http://cancerres.aacrjournals.org/content/74/19_Supplement/4513

    However, as the 779 preclinical experience seems to show, the overall situation is much more complex than the linker lability alone would imply.

    I do believe that IMGN share prices are pressured by a misguided investor perception of technical inferiority to SGEN and that it’s tantalizingly close to a major wholly owned source of revenue. It seems like SGEN had little little success in solid tumors whereas IMGN related products have had more traction in human trials.

    Its precarious cash to burn rate is a more pressing concern, but I like the moves the new CEO has made and propose.

    ARIA: Any thoughts about where Takeda saw the most value here? I’m thinking it’s Brigatinib?

  47. Hi Ohad

    It looks like STML going for approval of ST 401 for BCDPN in 2017 based on Ph II Study. Do you think the market for BCDPN is large enough for an increased valuation for STML? Their valuation is so low to begin with, what’s the fear? too small a market? competition for other ADCs?
    Do you think getting approval will attract any buyout offers?
    What do you make of their ongoing phase 2 for AML indication?

  48. Hi Ohad

    It looks like STML going for approval of ST 401 for BCDPN in 2017 based on Ph II Study. Do you think the market for BCDPN is large enough for an increased valuation for STML? Their valuation is so low to begin with, what’s the fear? too small a market? competition for other ADCs?
    Do you think getting approval will attract any buyout offers?
    What do you make of their ongoing phase 2 for AML indication?

  49. Hi Ohad, you had a good call on ARRY, it is a 2 digit stock as I write this. Unfortunately you sold too early. What do you think in the future of ARRY form here? the stock has doubled in no time. DO you think is a BO candidate by AZN or other pharma?
    Also, are you still bullish on ABEO? I have read very negative SA articles recently. Most probably is a short target but wanted to hear your view.
    Also, are you selling at any point your BIS or still not positive to the sector? Looks like bios are braking out.
    Disclosure: Long ARRY and no position for the moment in ABEO
    Regards

  50. Kevin (CLRB) – Don’t know them well but in general I’m not a big fan of the approach. Prefer the new directions pursued with ADCs (new payloads, conjugation techs, probodies etc.)

    Wildbiftek-

    IMGN – Kadcyla is a major success story (not as effective as I had hoped though) but beyond that neither company has a clear winner in solid tumors. SGEN’s bladder cancer data are exciting but need to be corroborated. IMGN’s meso data are also intriguing but sample size is too small.

    ARIA – I also assume it was brigatinib but still struggling to justify the price Takeda paid given the competitive landscape.

    roland (STML) – Sounds like the FDA were very supportive and the requirements for 1st line approval are very favorable. I guess there is a lot of uncertainty around market size given lack of approved agents plus safety profile with immunotoxins has always been challenging. I wouldn’t be too worried about competition given the challenges with CD123 bispecifics.
    I don’t have high hopes for their AML study. Efficacy as monotherapy was underwhelming imo.

    lgonber (ARRY) – They have an effective combination regimen but imo it will be hard for them to get significant market share as to me efficay profile isn’t differentiated.

    ABEO – Yes I am still bulish about them and very curious to see updated data next month. Can’t say their history doesn’t bother me but if the data hold it’s a risk worth taking imo.

    Gruber – Actually it is hard to find reasonably priced oncology stocks, even EXEL became expensive imo…

    Ohad

  51. Hi Ohad,

    o if you like ADCs why don’t buy some IMGN? 😉

    PGNX has a ADC programm too – but you only hold SGEN which is quite expensive ?

    CTMX also interesting company…

    Greetings

  52. Hi Ohad

    1. Any thoughts about FGEN and current valuation?
    2. Do you consider BPMC overvalued?
    3. Do you follow PIRS?

    Thanks,
    Chris

  53. ESPR

    Still depressed stock. Do you think it will climb in 2017 due to cvot results from amgn etc?

  54. OCRX is closely held, and it’s drug candidates for ammonia scavenging is unique in liver disease treatment. Seems extraordinarily cheap given the unmet need, and potential for buyout or deal like CNAT. Any thoughts on this company?

  55. Hi Ohad,
    Wondering what your thoughts are on some of the stem cell companies given our interest in gene therapy? Full disclosure that I own shares in Athersys- ATHX, Cytori- CYTX, and Avita- AVMXY, but I am much more interested in hearing any thoughts you might have on this approach to treatment more generally.
    Thanks as always to your generosity in continuing to share your insights with your community via this site. It has helped me greatly over the years and is a rare beacon of objectivity in a cyber-world full of hype and uninformed opinion.
    Jeff

  56. Hey Ohad
    Given its lie valuation I have initiated small position in QURE. This also in light of ONCE immunogenicity. Market cap is $32M!
    Any thoughts on VKTX? Market cap is $32M too. Two phase 2 programs reading out in 1h17. They have, similar to SAGE, LGND developed compounds.
    Thanks Dan

  57. Hey Don and Ohad

    regarding OCRX
    there are many companies in NASH space, some of them in ph2 with very low valuation:VKTX, CANF, GLMD among others.

    Not sure how come many companies like AGN, GILD and SHPG make huge investments when it seems there’s an array of smaller companies with excellent science that are valued so low: companies like ESPR, QURE, DMTX that seem so undervalued compared to peers. While biotech and pharma seem to be splurging and snapping up private companies…

    I feel that the better investments in biotech for 2017 will be in microcaps, here is a list of small caps I am following. Please let me know if you have any knowledge or opinions in any. Thanks.

    VKTX – NASH (drug competes with MDGL) and hip fracture testosterone-like drug
    APHB – cocktail of phages to treat CF – just had positive phase in rhinosynusitis
    GLMD – NASH in ph2
    QURE –
    RLMD – Ketamine-like drug
    VTGN – ketamine-like drug
    ATNM – DC33 drug competing with SGEN program (uses radioisotope, seems to be less cytotoxic)
    TRIL – CD47
    PIRS – anticalins – biven bispecific antibodies deals (MRUS) seems that PIRS should bring in more partners
    ENUM – io antibodies
    FATE – cellular immunoterapies
    MBVX – targeted antibodies
    CFRX – lysins that overcome antibiotic resistance

  58. horst (IMGN) – I am not against the idea in general given the low valuation and number of programs, I just wonder about the right timing.
    Agree about SGEN’s valuation but the bladder caner programs could become important catalysts this year.
    CTMX – On paper their technology has tremendous potential although some of teh ADC-related tox is not target-specific.

    Paul B (ADXS) – Not a big fan of cancer vaccines (even in the context of viruses)… Have to admit I don’t know them that well but overall not a big fan of the approach and I find the totality of their data quite hard to interpret (single arm, survival as an endpoint etc..). One thing I cannot argue with is the durable CR in one of the patients but there have been so many failed vaccines with such an index patient that eventually didn’t pan out so personally for me it’s not enough.

    Chris
    FGEN – I like the CTGF antibody as well as the HIF-PH program. Valuation is an issue though.
    BPMC – Strong believer in their approach although data so far haven’t been as exciting as I had hoped. Also here, valuation is too high imo.
    PIRS – Don’t know them well, not convinced their platform is superior to mAbs.

    Gruber (ESPR) – I sure hope so. Upside is huge if things go well given the low EV.

    Bionerd (MRNS) – Not strong opinion, tempting as a binary option play later in 2017 with PPD data.

    Don (OCRX) – Sorry don’t know them well.

    Will answer the rest later today

    Ohad

  59. TRVN

    Valuation low in front of key catalyst in Q1 2017. Do you expect much upside when trial suceeds? Maybe the market for olicerine not as broad as expected?

    Thanks

  60. Ohad: Love your work, I have a similar question as Vilor around TRVN Valuation. Assume that TRVN phase 3 shows itself to be as advertised, effective as morphine with less Respiratory Depression and stomach issues. I would think if TRVN captured even a small % of the market that would be big. Then….I would almost think the lawyers would drive Doctors into Oliceridine, “you had the opportunity to prescribe a safer drug yet chose not to do so?” However, people are talking TRVN down implying that a Positive phase 3 would result in simply status quo in terms of stock price. You don’t have a crystal ball, but am I misguided to think IF phase 3 results are good, that would result in big upside for TRVN? Thanks, Matt

  61. hey Ohad
    have you listened to a ER conference by the ABEO CEO? does he sound like he is legit?

    Dan

  62. Jeff – Thanks. While I’m cautiously optimistic about gene Tx I am not excited about stem cell companies as they are highly complex, face significant challenges and are not clinically validated. IMO it will take years until the stem cell field reaches maturity, hope I’m wrong.

    Dan –
    QURE – Agree about current valuation ascribes very little value to the technology but it is hard to envision how they compete in hemophilia and the CV programs with BMS are very early.
    VKTX – don’t know them well.

    Dan – NASH is viewed as the next frontier by many companies, which are willing to pay generous premiums for preclinical assets or clinical assets with ambiguous results. Gene Tx is still not palatable to many large companies, agree about ESPR representing an attractive takeout candidate but their drug will be another LDL-C lowering drug vs. NASH drugs that have the potential to open up a huge market with no approved agents.

    Alex – I don’t use stop loss

    Vilor (TRVN) – Yes I expect a significant move if data are positive but I agree that questions around market acceptance will probably linger. Market opportunity is broad based on amount of opioids used after surgery, however, TRVN’s market share is still hard to predict.

    Matt Bailey (TRVN) – Thanks. I completely agree with your assessment of the market, there should enough incentive from hospitals, physicians and patients to allow TRVN to capture a meaningful market share especially in high risk populations but only time will tell…

    Dan (ABEO) – I sure hope so… Will wait for next month’s data to decide

    Ohad

  63. Hi
    Ohad

    Which stock in your portfolio is your favorite at this time ? What are the next catalysts for this stock ?

  64. Ohad

    given all the talk about NASH.would you recommend AGN which made several NASH deals and/or ICPT which is a pure play on the NASH market?
    any other names we should be looking at in the NASH market?

  65. ARRY

    What a nice chart. I also sold too early:(((

    Whats your favourite b/o target right now ? TRVN ESPR?

  66. Ohad
    STML has a clear path for approval w/ their BTD, BLA in H2, potential approval – mid 2018.
    The risk looks low, comparable to LOXO, the same for the addressable market .
    But LOXO has 5x the market cap?!
    Am I missing something? Is there any particular reason for this discrepancy?

    BLCM – also looks weak after ASH, nevertheless they presented solid data –
    “All 35 children treated are alive, free from GvHD and cured of their underlying disease” – That’s 100% CR rate to me, no?

  67. Ohad
    Any interest in SELB? A sort of gene theraply play, I guess. Good deal with ONCE.
    If their SVP technology could solve the antibodies neutralization issue, it would be an effective way to increase the dosing and for re-dosing.
    Thanks

  68. Ruhu – Hard to choose a single stock. As you know, I like the gene Tx basket and also cautiously optimistic about TRVN’s P3 data.

    dave – Difficult to answer as I don’t know the NASH field well. II am somewhat skeptic about this segment as the disease is quite complex, not always well understood, and there are no clear biological drivers (as opposed to oncology and genetic diseases).

    Gruber – Historically I’ve been lousy at predicting buyouts… People are talking about BMRN, which sounds like a good target to me at its current valuation. INCY and EXEL are also very popular names given the scarcity of commercial oncology assets. TRVN and ESPR are very cheap and their drugs are de-risked but they are less in the biopharma sweet spot.

    andre (STML) – I agree things look good but can also understand why LOXO’s valuation is much higher. LOXO’s response rate and durability is better (completely different indications), its drug is a validated class (kinase inhibitors) and safety profile is less of an issue. It also has multiple programs based on the same rationale as 101.

    BLCM – Agree. Data looked good.

    andre (SELB) – Anyone who will solve the problem of neutralizing antibodies will have huge value in gene therapy. Definitely worth following but will take time to clinical proof of concept.

    Ohad

  69. Good morning Ohad!

    What do you think about AGIO at current valuation? Shares fall since december when Agios discontinued their AG-519 programm. Now it looks like the market is concerned.

    Thank you in advance!
    Martin

  70. Hi Ohad. Wonder if you’ve looked at Exel’s pancreatic cancer results from Asco GI. Looks intriguing, though obviously highly inconclusive.

  71. hey Ohad

    Just curious, like others here, about how to play TRVN into binary event. There has been a surge in the share price but it is still very much deflated.
    In the event of positive results, what would be the likely scenarios? do you think some larger co. in pain would buy them out? Or do you see TRVN going it alone and trying to morph into a commercial company?

    Thanks
    Dan

  72. ARRY CLVS

    You picked the right oncology stocks but had a bad timing. Also AUPH is rising again.

    You would reenter thisstocks or avoid?

    Maybe these oncology names are interesting: tsro (buyout), stml, imgn

    Greeting

  73. Ohad
    AUPH: Adam F has an interesting interpretation about the unbalanced deaths in the voclosporin study, which was the main reason you exited the stock after their data last August (myself included :)). One of hos strong arguments is that the dead imbalance is not collaborated by AE imbalance.
    AUPH may release the data in mid Feb. Do you think it’s worth the risk to get in before the data?

  74. Hi Ohad

    What is your current view on ALNY and CLLS in terms of technology and valuation?

    Many thanks
    Kevin

  75. Hey Ohad
    INCY has performed well, and they seem to be relentless in adding pieces and product candidates. After the MRUS deal, now it’s CALA. Is this a new GILD or CELG in the making? Also noticed they are developing an in-house PD-1 drug.
    Dan

  76. Martin (AGIO) – I still think it’s a little pricey. The AML programs are effective and approvable IMO but I find efficacy a little disappointing for a biomarker-defined indication. MTAP is very intriguing and can be huge but that’s a 2018 story.

    PaulB (EXEL) – Agree.

    Seu (XLRN) – Valuation is still too high imo. I like the MDS program where they have a clear Hb effect and competition is limited but a lot of unknkowns especially long term safety profile. Not optimistic about the RCC program…

    Dan (TRVN) – I wish I knew… My sense is that it will take time for the story to unfold so a positive outcome will not lead to a 3-4x jump instantly. Eventually they will have to partner with a partner who has commercial footprint but they can start like PCRX until they reach critical mass.

    Seber (ARRY/CLVS) – That’s true but timing is as important as picking the right stocks.

    Andre (AUPH) – I still feel uncomfortable with such an imbalance, regardless of AE rates.

    Kevin
    ALNY – Agree it’s tempting at its current valuation given cash position and GENZ deal. Still not sure whether the overhang re: platform is completely removed.
    CLLS – Prefer not to comment on CAR companies.

    Dan (INCY) – Yep, they are certainly expanding their pipeline and setting the foundation for a significant biotech. Personally, I think they are taking very early or less validated assets that come with a significant risk but on the other hand, this is what they can afford to buy in cash.

    Ohad

  77. Ohad – thanks as always for the insights. I read this post a while back but I’m here again to ask a question this time.

    What are your thoughts on TCON?

    I’ve just started DD on the company and management, partnerships, science, data to date, and market cap make it a pretty interesting company to look at. They have tons of data coming out in 2017 and 2018.

    It reminds me a lot of ARRY last summer. Multiple shots on goal and small cap with a low entry price.

    Be curious to know if you’ve done any DD on this company and what your thoughts are. I always appreciate your wisdom around the cancer space.

  78. hey Ohad
    I think that INCY is doing more than buying what they can afford. They are expanding their capabilities (antibodies, bi-specific antibodies) and going after the things they know well: the CALA licensing deal follows their expertise with IDO drug and the promise of I/O combinations.

  79. Hi Ohad,

    ESPR – never thought this stock would go down this way. ATM share price $11 – do you recommend buying at this level? i see you still hold this stock in your portfolio. if things go well its a tenbagger?

    Oncology stocks – i want to invest in a basket of stocks like INCY, TSRO, STML, SGEN, IMGN, CTMX – are these good names?

    Thank You.

  80. Hey Ohad
    DMTX results in… seems they have not managed to achieve sustained 10% FIX levels,
    also various AEs. What’s your take? how do the data compare to other GT cos?

    Dan

  81. Ohad: After digging as deep as I can on TRVN, I have decided to keep my TRVN holdings thru phase 3 results. However, I do have a question about the 900 person Safety trial on-going called Athena. The patient can be dosed with Oliceridine for up to two weeks. If Phase 3 comes back in spectacular fashion on efficacy and safety as I hope. Can you help me evaluate the risk with the Athena(safety) trial? I would imagine 900 people taking Oliceridine for up to two weeks has a higher probability of disclosing safety issues if any exists. If you are willing , would like to hear your thoughts on these two questions:
    1. How much risk would you associate with the Athena trial? I realize “how much risk” is very subjective.
    2. Assume the Athena trial does uncover a safety issue that was significant. What would be your best guess on the specific safety issue that gets raised.

    I respect your work and view, my hope is to take your view to help me dig deeper and then decide if I hold thru the Athena trial assuming P 3 Apollos trials are good. My understanding is that the Apollo trials will be in before Athena. Thank you for your work and sharing. Matt

  82. Hi Ohad

    DMTX: As I understand they use their prop tech vectors for the hemophilia programs, the rest is from RGNX (e.g. AAV8 for OTC). On the back of this and given that they are trading way below cash might be good entry point now? Is there any data to be expected this year for OTC?

    Many thanks
    Kevin

  83. SAGE, AVXS

    What are the key catalysts youre waiting for in 2017 for valuation?

    Thank you

  84. Hey Ohad.

    What do you think of EXEL partnering deal with Takeda?

    Does BTD for QURE chang anything there?

    Thanks

  85. Ohad
    do you follow BGNE? They claim that their BTK is more selective and so with less AE. The responce rate so far was good – 83%. They just started Ph 3 with comparator ibrutinib – pretty bold move
    Plus a number of other earlier assets – PARP, RAF dimer and PD-1.
    The valuation is high, but is it justified by the pipeline?
    Thanks

  86. Hey Ohad
    any opinions on ESPR competitor GEMP wich has a phase 2 with positive intermediary results:
    300mg dose reduced LDL-C by 23%
    600mg dose by 28%
    benign profile until now
    They are also going after NASH (with p2 trial starting imminently).
    Valuation is $100M.

    How do you think their drug compares to ESPR’s?
    Thanks
    Dan

  87. Nick (TCON) – I was going over the Jefferies initiation report from Dec and I agree about the eventful 2017 and low valuation. My main reservation has to do with the fact that all efficay date to date is from single arm trials in combination with active drugs so very hard to interpret. In any case, I would wait until the GBM data early 2017 before initiating a position given the very high risk in this indication.

    Dan (INCY) – Agree about expanding capabilities and platforms, the main issue is the long timelines to get clinical proof of concept.

    Salamander –

    ESPR – Yes I am still bullish (and deep in the red). Agree about the upside potential given low EV and the derisking from Amgen’s CVOT data.

    I like all the oncology names you mentioned, my personal preference is towards the smaller ones. Hard to justify INCY’s and TSRO’s valuation IMO.

    Dan (DMTX) – Data were weak and their vector doesn’t look competitive. Doesn’t mean all is lost for their earlier programs but definitely a major blow.

    Alex (DMTX) – I don’t think it has any implications to other platforms.

    Matt Bailey(TRVN) – Long term safety studies always carry a significant risk especially in non-life-threatening indications. It is very hard to predict the extent of risk because even a very low rate of severe adverse events could jeopardize the entire program.

    Kevin (DMTX) – From what I understand their metabolic programs use different vectors and capsids to read-through is limited.

    Marcmagic
    SAGE – The most important event is P3 readout in SRSE
    AVXS – Updated data from P1 in SMA1.

    Gurtus (STML) – Quite troubling and doesn’t help investor confidence either…

    Ike (EXEL) – Deal was not as rich as I had hoped, plus it implies no imminent M&A. I thought the deal would push the stock down but it’s breaking new highs…

    QURE – Not sure because it doesn’t solve competition.

    Varkler (ESPR) – Yep, assuming the benefit is clinically meaningful this is a major validation of the LDL hypothesis.

    Bouschka (GEMP) – It’s been a while, will take a look.

    andre (BGNE) – I prefer to focus on companies with first-in-class or differentiated products.

    Dan (GEMP) – It’s been a while, will take a look.

    Ohad

  88. Stml

    Do you guess that the fda will hold the trial due to the 3rd death?

    Bpcdn still looks good . other indications maybe suffer from the. AE?

    Stml at $6 a good buy right now? How bg is the risk?
    Thanks

  89. Ohad

    When you comment regarding AMGN CVOT studies”assuming the benefit is clinically meaningful” do you think a HR <.70 is something you expect or is that being too optimistic.

  90. Hi Ohad,

    Have you looked at CRIS lately? you used to have a position once. Any thoughts?

    Thanks,
    Chris

  91. Looking back at Pfizer’s call to discontinue their Ph3 PCSK9 mAb, do you think this was a great call (esp with the Amgen lawsuit)? And having not purchased a program to account for their PCSK9, do you believe Pfizer is deficient in terms of next generation LDL-C therapeutics?

    Thanks,
    Garry Xo

  92. Ohad
    The deal b/n SGEN and IMMU looks pretty good for both companies.
    IMMU solved thier main problem – cash. How do you value their two ADC programs? I am sure you are not excited about their main CD22 program.

    Do you follow AGLE?

  93. Fmi

    Breakout – any reason for that? I see u still hold this stock.

    Roche buying the rest of shares?

  94. Kolos (STML) – Hard to say but given history with immunotoxins, liver toxicity very troubling and the risk is higher right now.

    Dave (AMGN) – I think a 20% reduction should be regarded as very positive.

    rodolfo (RDHL) – Sorry, don’t know them well.

    Alex (EXEL) – Only a spectacular Q4 sales report

    chris (CRIS) – Actually no… I guess most upside still depends on the PD-L1/VISTA small molecule, which represent an interesting approach but very risky and not validated.

    Garry Xo (PFE) – I think they made the right decision given their timelines and tolerability issues. Yes, I think they are deficient in LDL-C lowering drugs but it doesn’t mean they must have one…

    andre (SGEN/IMMU) – I think the deal is great for IMMU but not for SGEN. Despite the BTD, I don’t think data in TNBC justifies 250M upfront.

    Not following AGLE

    Yussu (FMI) – Yes, stock is behaving nicely, don’t know why. Don’t think Roche will try to buy the rest of the company without good visibility on reimbursement.

    Swetz (ESPR) – Hard to say. I hope that Repatha’s CVOT data will help changing the sentiment around the stock. 2017’s primary risk is emergence of safety issues in their P3 studies and the primary upside is a buyout given the low valuation.

    Suberus (AFMD) – So far, data using NK for IO has been disappointing so I am not optimistic there. Innate Pharma’s recent failure with anti-KIR is a negative read-across for the entire NK field IMO.

    Ohad

  95. How +ve are you on TRVN ? I read a article CARA vs TRVN, what are your thoughts ?

    Thanks again Ohad.

  96. Ohad – your analysis of TCON was absolutely spot on. I forgot that I posted here and forgot to check back. But when I did, I realized that you posted about waiting for the GBM data. Great call on that. Luckily I didn’t bite yet, but I think it may be a good entry point now given that we got the tough stuff out of the way.

    What were your thoughts on the data? What is your strategy on this stock?

    I’ll share mine too: I plan to start a small position on this at 3.8 if I can rally into that. I’m going to continue adding in the 3’s if I can and play a run up into the next dataset. I’ll likely sell a few shares then and let a few ride out into the dataset. I’m very excited about angiosarcoma and think that it has huge potential to validate the MOA. If so, there is potential that this product has activity in a number of rare conditions (as well as some big ones like NASH for example).

    I always appreciate your thoughts sir.

    Nick

  97. Sage

    Do you think sage 547 has a high likelihood to suceed in p3 srse? I have my doubts.. Maybe reenter after announcemenf of the results. How do you see the risk?

    Thanks

  98. ARQL

    Isn’t it now time to buy ARQL after the failure of the METIV-HCC Phase 3 Study of Tivantinib?

    Regards
    Toby

  99. Hi Ohad,

    IMMU: There are other promising indications besides TNBC, take a look at mUC:

    http://meetinglibrary.asco.org/content/179208-197

    where ORR is 36% (confirmed). This compares favorably even against recently released Cabo+Nivo:

    http://meetinglibrary.asco.org/content/179687-197

    where the more successful Cabo+Nivo arm (rather than the triplet w/ Ipi!) achieved of ORR 38%. Toxicity seems manageable as well. Other tough to treat indications like NSCLC and SCLC are showing good results too but it’s tougher to think of where it may fit in w/o a combination w/ a PD-(L)1i.

    I think the company was dragging its feet and did need a swift kick in the ass from activists, but they really do have a promising asset in IMMU-132 and finally the funding to get it approved.

  100. Curious about ARQL as well. Interesting call from Feb 17 (on website). PIII IH-CCA this summer; discussion with FDA & EMA and approval endpoint is > 10% response rate, 90% CI and 6 month durability. Also initiating P1/2 in Proteus+other overgrowth independent of NIH and P1 for next gen BTK. $30M cash + $50M recent debt to run the studies. Company has good management.

  101. Any thoughts on AGEN ? Especially now- after the amendment to its collaboration with Incyte? Is this an unreasonable entry point?

  102. Any thoughts to add more SAGE at current price based on the recent positive data of SAGE-217 on MPP? Your thoughts are appreciated.

  103. Bouschka – (GEMP ) – Not yet…

    Chris (CTMX) – Yes because they have a technology that can be a real game changer but stage and valuation keep me from buying.

    Alex –
    STML – I still have some but more cautious after teh death they reported
    EXEL – Nope. It was hard but I sold all my position (see today’s portfolio update)

    Alex (BVXV) – Sorry don’t know them well.

    Ruhu (TRVN) – I am still positive on TRVN and think they have a superior product for post-operative pain. I like CARA and their mechanism (kappa agonism) for pruritis and think they have an effective agent but still not sure about their oral formulation, which is important for chronic indications.

    Nick (TCON) – Thanks. I still think their studies are very high risk because it is hard to distinguish their antibody’s effect when combined with effective treatments. The angiosarcoma case study is very intriguing but for me it’s not enough.

    Glaub (SAGE) – I think it has a fair chance of meeting the 1ry endpoint but today te story is shifting towards depression after the PPD and MDD data with 547 and 217 respectively. So if SRSE fails, I agree it could be a buying opportunity.

    Toby (ARQL) – Agree and just added to the portfolio. Good risk /reward at <$100M market cap. Les (ESPR) - I think people are starting to realize they may get approval based on LDL and that there is a market between oral generics and PCSK9 that can be addressed by bempedoic acid. Wildbiftek (IMMU) - I was always struggling with their data, never smelled right for some reason... Manish (ARQL) - Agree. If one of their programs succeeds this is a 10x opportunity, but stock is still very risky so I intend to keep my exposure low. lawrence (AGEN) - I think they did a great deal with INCY but the assets are too early and not differentiated. Jinyu liu (SAGE) - Still haven't decided to add before the SRSE readout. As discussed above, now that depression is becoming more interesting, perhaps it's safer to wait and add after the data. Kevin - Today Hard to find the time but hope to post more frequently Ohad

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