Gene therapy updates – One big acquisition, two IPOs and a mixed bag of data

It is hard to overestimate the impact of the Novartis (NVS) /Avexis (AVXS) deal. So far, big biopharmas have had limited exposure to gene therapy and those that did get into the field focused on early-stage collaborations: Pfizer/Bamboo, Biogen/AGTC, Roche/ 4DMT, Abbvie/Voyager etc. This is understandable given the unique product profile gene therapies represent: One time irreversible treatment, lack of long term follow up and creative reimbursement models.

The $8.7B acquisition of Avexis, just three months after the deal with Spark (ONCE), makes Novartis the first pharma to embrace gene therapy as a commercial opportunity. The deals also make Novartis the undisputed gene therapy leader with (hopefully) two products on the market next year.

Investors continue to pour money into gene therapy IPOs. In January Solid Biosciences (SLDB) managed to go public despite safety concerns raised by the Jim Wilson, and Homology Medicine (FIXX) completed its IPO last month, raising $165M. A third company, Rocket Pharmaceuticals (RCKT), raised ~$78M following its merger into a public shell.

Gene therapy stocks are understandably very strong as investors are excited with the Avexis deal, but looking back on the last 9 months, actual data from gene therapy programs haven’t always been that exciting. I went back to the list I put together in July and the overall performance wasn’t stellar…

Audentes – Exciting data from a single patient

Audentes (BOLD) stands out as the winner with very early but encouraging data in XLMTM, a rare muscle disease. The most striking finding came from the first patient in the study (9 months old) that included a dramatic improvement across two clinical scores (covering neuromuscular and respiratory function) at 12 weeks post-treatment. Importantly, the scores obtained after 12 weeks were approaching those seen in healthy children.

The second patient (~4 years old, higher baseline performance) experienced milder improvements after 8 weeks of follow up and did not demonstrate an improvement from week 4 to week 8 but still reached the same neuromuscular score (CHOP-INTEND) reported for patient #1. Data for two additional patients didn’t demonstrate significant improvements but follow up was limited. One reason for concern was elevated troponin levels which may indicate an immune reaction against transduced cells.


Next update will be crucial in order to understand robustness, durability and long term safety profile. If the effect is corroborated and maintained in additional patients, XLMTM could be the first muscle indication to be treated with gene therapy and a proof for AAV8’s ability to target muscle cells (on top of liver). The next big muscle indication for gene therapy is obviously DMD, with multiple programs currently in P1.

Mixed data from Voyager, REGENXBIO and Ultragenyx

Voyager (VYGR) – Updated data for VY-AADC were mixed as all three dose cohorts demonstrated signs of efficacy but cohort 3 did not perform as expected and there was no dose-dependent response.

VYGR - Dyskinesia

REGENEXBIO (RGNX) – Limited update from RGX-314 in AMD, only disclosing safety profile looks good and that there is dose dependent expression of the protein in the eye. Full data set is expected later in 2018.

Ultragenyx (RARE) – Updated results from the OTC program (DTX301, AAV8) started to show early signs of activity after a previous disappointing readout. Of the three patients who received the lowest dose of DTX301, one patient achieved a durable improvement in urea production (OTC deficiency is characterized by impaired urea production) and discontinued background medications. The two other patients did not achieve any improvement, so hopefully higher doses will be able to improve rate of clinical responses.

Setbacks – GenSight, Spark, Solid Bio

GenSight –reported negative results from its P3 in LHON, a rare ophthalmic indication. Although expectations weren’t high judging by the company’s market cap, this is still one of the largest randomized studies for gene therapy and continues to question using intravitreal administration with AAVs.

Spark – reported underwhelming data in Hemophilia A (in contrast to my bullish prediction) but the stock recuperated since thanks to positive sentiment around gene therapy and encouraging comments by management about future data.

Solid Biosciences – The company’s lead program was put on clinical hold following a severe adverse event in the first DMD patient who received treatment.  Solid’s safety issues appear vector-specific (Sarepta’s DMD program is recruiting without any major issues) but are a painful reminder for how risky the field is.

Crucial year ahead

The remainder of 2018 will have important readouts from over 20 studies. By year-end, investors should have a better understanding of whether the current enthusiasm is justified…

Portfolio holdings – April 16, 2018   

Biotech portfolio - 16-4-18biotech etfs - 16-4-18 

109 thoughts on “Gene therapy updates – One big acquisition, two IPOs and a mixed bag of data

  1. Hi ohad, which Main catalysts/readouts do you See for gene Therapy in 2018/II? Thanks

  2. Hi Ohad,

    Does GenSight failure have any readthrough to ADVM amd program? I realize different disease but you mentioned calling into question “intravitreal administration with AAVs” which ADVM is doing with their AMD program in contract to RGNX’s sub-retinal approach?

    Thanks for great insight as always!

  3. Hey Ohad
    Thanks for the reply. Seems to me that TRIL is making progress while their valuation is still low.

  4. Hi Ohad. AGTC has finally made an upside move and issued two press releases updating full enrollment of XLRS and first dosage in XLRP. Are u still bullish on AGTC? I see u are still holding. Like u said GT is hot now and AGTC does have a few shots on goal with their pipeline.

  5. Ohad, I see you have a fairly large position in XENE? Does that reflect your confidence in XEN1101? If XEN1101 can replicate Ezogabines efficacy without the pigmentation issue, they’ll have a very attractive drug. Thank you

  6. Hey Ohad,
    How would you compare NITE and AGTC considerid they are pursuing this same indication? Is there room for two or three x-linked retinitis pigmentosa therapies, or is the market too small?

  7. Ohad
    Do you have an opinion about MOR?
    They have antibody targeting amyloid plaques- Roche is running 3 Phase 3 trails for Alzheimer’s disease.

  8. Hi are you familiar with ALBO? not ‘cheap’ but they have cash. very rare disease.

  9. Ohad

    The sell off of SAGE yesterday seems like a overreaction.Its been attributed to Biogens deal with IONS. Do you view this as a buying opportunity, or is the valuation to high to commit further funds too?

  10. Biohero – A lot of updates from existing programs, I think most companies should have updates. The ones I am most intrigued about are for muscle diseases BOLD and preliminary update from SRPT. ONCE should have important data in HemA and ABEO for their 2 Sanfilippo programs. Also curious to see RGNX’s AMD data as they state they see dose dependent expression of their protein.

    Mike (ADVM) – Indeed different indications but it adds risk on an already risky program (even subretinal admin didn’t work so far).

    steve (FMI) – Good question. I completely missed the IO applications of their technology especially as liquid biopsies. Valuation is kinda high though…

    DAn (TRIL) – Yes, but they still need convincing clinical data…

    Luigi (AGTC) – Exactly, it’s all about a broad exposure to the field. Hard to predict who will be the next AVXS… Personally I like RPGR as an indication but follow up takes more time. NITE also has a program in P1.

    Shane (XENE) – Agree, which is why I am still holding. Hope to publish something on them next week.

    Christian (ARNA) – No strong opinion, definitely a great turnaround move.

    DAn (NITE/AGTC) – There is some overlap but the two companies have additional programs so I prefer to own both. XLRP is relatively big so there is room for more than one product, I just hope at least one of them will be clinically beneficial.

    andre (MOR) – I wouldn’t hold my breath for an A beta antibody…

    don (ALBO) – Wasn’t aware of them, just got the Jefferies initiation so need to dig deeper.

    Dave (SAGE) – I also think the market over-reacted. I plan on holding as the commercial opportunity in depression is huge.


  11. Hi Ohad,

    Do you see any reason for VKTX weakness recently? I see you hold 2000 shares

    Thanks, Chris

  12. $BIOC What do you think of Biocept, it is also a diagnostics company that has an agreement with Thermo Fischer.

  13. Ohad
    any concern about NERV 5HT2A MOA based on the ACAD issues with the same receptor.

  14. Hi Ohad, Gnpx doubled today. As a gene therapy player what is your take on them? As always thank you for your insights. Peter

  15. Ohad and Peter,
    Gnpx has been on a tare. Hadnever heard if them.

    Any opinions on CVM – they are in phase 3, fully enrolled. I suspect you will not like them because they use neo-adjuvant for IO. However, might merit a closer look?

    Thanks! Looking forward to reading your piece on XENE!

  16. Hey Ohad,
    Are you familiar with Israeli company CANF- they are pursuing adenosine receptor antagonists for NASH and HCC. Any opinions on that target? The product candidates have a very good safety profile which is supposed to bodd well for NASH (combination therapy). Thanks for your help! DAn

  17. XENE XEN1101 Kv7 opener – data at Eilat 2018 (13-16 May). Is the recent share gain related to that?

  18. Ohad….Toca released some Glioma data recently…some views were positive some negative…also signed a licensing deal recently with a China bio for 20mil upfront…then it tanks…curious your view on whether its the data or sell the news senario?

  19. Thanks for your feedback. Is there life yet in old INFI? Can ipi-549 be their turnaround story? thanks

  20. Hi Ohad
    what are the pros and cons for buying EXEL now?
    would you add SNSS or VKTX at those levels?


  21. Hey Ohad,
    Any opinions on the ESPR PR? seems like the market is not impressed with results and unexplained deaths (0.9% vs 0.3% in placebo group)

  22. ESPR
    3x mortality imbalance, 50% increased discontinuations
    I think you sold AUPH due to similar increased fatalities.
    Are going to hold ESPR?

  23. Text of their release indicates ‘no difference’ with the placebo group. Details – There were no clinically relevant differences between the bempedoic acid and placebo groups in the occurrence of adverse events (AEs) with 78.5 percent and 78.7 percent, respectively; or serious adverse events (SAEs) with 14.5 percent and 14.0 percent, respectively. Liver tests were more elevated than placebo.

    Management seems cool and indicated business as usual. Really looking forward to Ohad’s Analysis on this very painful day :-(

  24. Les
    13 deaths in the treatment group compared to 2 in the control group.
    May not all be treatment related though….

    I am also curious to see Ohad’s response
    Last time when such death imbalance appeared (AUPH) he sold all shares.
    It is not a cancer drug and FDA is very brutal in such cases.

  25. Andre – guess the % of deaths (SAE) were the same (14%) as the details I posted indicate? Absolute number is different but size of the groups may be different or are they the same?

  26. ESPR seems to only be dropping gut wrenchingly lower after a little bounce from 44. Hope management clarifies and there is a bounce tomorrow.

  27. well there was also a second pretty bad news on ESPR in my opinion, namely the cheap Praluent price for Express Scripts customers. I read something about 4.500 to 8000 USD a year. Sure the pill can be cheaper, and convenience is in favour of ESPR. I think ESPR hinted at a price of 3.600 per year, but it could easily be this is not cheap enough when you compare effect size to Praluent …

    that together with today’s news was enough for me to pull the trigger. I managed to get out close to the highs of today…. move on.

    anyway I am not a specialist for ESPR

  28. Ohad

    Did you ever get the chance to look at CWBR? There programs are based on mitochondrial peptides. Dosing 1st patient in June based on there last conference call. Seems to be overlooked in the NASH field, and other possible large indications. Extremely early but the founders of the company have exquisite resumes. Would appreciate any comments you may have.

  29. Hi Ohad,
    Huge disappointment from ESPR Management touting positive data while in fact not providing any information regarding death cases. We’ve had some red flags before though when the company knew about the CVOT and didn’t disclose. Transparency issues obviously. Seems they got a long way to recovery.
    Doyou plan keeping your position?

    Thanks, Chris

  30. Hi Ohad,

    On the happy side EXEL has a huge beat… 37c vs 16c. At $22 it is heavily undervalued. Your thoughts?

  31. Chris (VKTX) – Not aware of anything in particular. Perhaps readacross from MDGL.

    curiousperson (BIOC) – Sorry don’t know the Dx field well.

    andre (NERV) – Not sure their issues are related to the target but definitely something to watch.

    Peter (GNPX) – It’s an interesting story on paper but very challenging in terms of delivery to tumors imo (using nanovesicles)

    DAn – Sorry not following either of those names.

    Andre (XENE) – Hard to say, they should have the data in house so perhaps.

    RobertGoulet (TOCA) – I think these data are always hard to interpret without a control arm. Not a big fan of their approach.

    don (INFI) – I am following it because it is an interesting story scientifically but the combo data they will generate will be hard to interpret (IDO is a sad reminder).

    Luigi (CRSP) – They are clearly making progress but valuation is too high for me.

    Alex (EXEL) – The RCC franchise looks strong but I am not optimistic about the KRAS+ CRC study
    No plans to add SNSS or VKTX until they release new data.

    DAn/andre/Les/Chris (ESPR) – The death imbalance is quite troubling even if it can be explained and deemed not drug related. Still didn’t have a chance to hear the webcast but this time I understand the market reaction, the FD doesn’t like to take any risks…

    Christian (ESPR) – I actually don’t find the Praluent story troubling. Patients who don’t need a dramatic LDL reduction will still prefer an oral drug imo.

    Dave (CWBR) – Wasn’t aware of them, thanks. The weight loss data in animals look interesting, not sure if an injectable with a short half-life is competitive enough in today’s NASH environment though.

    Les (EXEL) – I still think they need another catalyst and the next big one in CRC will be negative IMO.


  32. ESPR – “Two of the patients out of the 742 who received placebo died; 13 out of the 1,487 who received bempedoic acid died”

    the drug group was twice as big..maybe i’m wrong but it seems like a fluke

  33. Hey Ohad,

    ESPR: the 24 week Ph3 study (Clear Serenity) will be reporting this month. Hopefully that can reassure investors, bring some serenity again, thought it is most likely that everybody will be waiting to see the second 52-week study results, and then open label extensions. But there are plenty of near-term catalysts: all of the ph3 studies will roll in between now and September.
    What is your strategy? Are you holding hoping the results reported yesterday were a fluke?

  34. hmmm, ADVM news release of leadership change, Ohad, have you read??? What is going on there…?


  35. Hey Christian,
    I agree with you, there has been some hubris from management that has sometimes made the company unnerving.

  36. Ohad
    what do you think about SRPT deal w/ Myonexus to advance 5 GT programs (2 clinical + 3 preclinical). It looks they are using the same AAVrh.74 vector used in the micro-dystrophin GT.
    Does SRPT fit now into the GT basket or is too expensive (5B). I like their focus on muscle diseases.

  37. Dan, I haven’t followed the company much, but is the abrupt departure of CEO and CMO of worry to you (in a sense that it could be related to progress etc. of their drugs)?


  38. Hi Ohad et al,
    Any comments on GEMP based on ESPR results? They have had a similar range of effectiveness as ESPR (30% reduction at 300+mg LCL-C levels and ~20% at 130mg) in initial clinical trials and indicate they are going to next steps. Safety profile has been reported as excellent. ESPR and GEMP teams seem to have common roots linked to Pfizer. Also MDCO reported great trial efficacy results recently – any comments on their prospects?

  39. Ohad,

    Here is a nice link for cross trial comparison cotezo vs Regorafenib

    Quote from Ernie

     The only statistic where Stivarga looks better is PFS, 2.0 vs 1.9 months.  That is not an unusual circumstance.  I/O tens to underperform in PFS and do better on OS.  Cotezo looks better on ORR, 8% vs 1% and OS, 10.0 vs 6.4 months.  The responses were durable and the Cotezo patients more heavily pretreated.  

    My note

    Also of note 44 patients with mss had median OS of 13 months, 95% of cotezo arm in pivotal phase 3 is mss. The breakdown of prior therapy for mss patients was not broken down, but by my math at least 70% or more had 5 lines or greater when you factor 66 out of total 88 patients has 5+ prior systemic therapies in phase 1b study

    It speaks to the confidence Roche has that they enrolled 120 in each cohort. Very small trial!!! Roche isn’t going to underpower a study like this and risk failure due to underpowering.

  40. Hi Ohad, any thoughts on KPTI? Potentially a novel way to treat cancer and other diseases.

  41. Ohad have u considered MBIO?

    Signed a deal with Harvard to develop the first CAR-T/Crispr Combo molecule

    Also have the first CAR-T to show efficacy in solid tumor…yes no control arm

    Def plenty of competition for them, low evaluation probably reflects this, but if they can get one of their 6 molecules ahead their value could show considerable MCap increase

    Also your thoughts on NTLA?….def much lower MCap then their competition


  42. ESPR

    Ohad, do you see the recent selloff as a buying opportunity for people who aren’t invested in the stock yet? Thank you

  43. BPMC is said to have some good drugs, but all early (P1…) and valued at 3,5 billion?!
    Ohad, have you looked at them?

  44. Hey Ohad, Ambit’s drug passes first ph3 trial… When is Daiichi’s CVR triggered!

  45. @RobertGoulet:
    Also came across MBIO recently – seems to be quite early stage, interesting that they already have secured their own production facility as I understand… management team seems to be decent too, still will probably still need significant financing this year…

    Curious to hear Ohad‘s view

  46. Blast from the past!
    AMBI: Basically one CVR for first US sale in second line (which seems quite sure after todays results) and one for first line. (Think there is another P3 running) Each CVR 2.25 so 4.5 in total.

    CLVS just got back EX-US rights for lucitanib from Servier. I am very surprised! Thought this program was dead also find it strange for CLVS to get basically European rights? Any thoughts Ohad?

  47. Alex (ESPR) – Even if you factor in patient numbers there is still a numerical imbalance. I agree it looks like a fluke going into the details but it’s still a red flag until resolved in future readouts.

    DAn (ESPR) – Yes I am still holding as I think results are probably a fluke but burden of proof is on the company and the overhang is still there.

    Christian (CTMX) – Good concept and technology, too expensive without clinical data.

    ADVM – No idea but they should have interesting monkey data for their intravitreal vector at ASGCT.

    andre (SRPT) – Good for them, they are in licensing a lot of interesting GT programs. My main problem would be valuation as you stated.

    Les (GEMP) – Need to re-visit GEMP but after evaluating both I was clearly on the ESPR camp. Still licking my wounds but I plan on to hold.

    Chris (EXEL) – Can’t argue with that but no matter how smart Roche’s clinical folks are (and they are) they can’t predict the future and so far the only information they had is from a single arm combo study.

    Xavi (KPTI) – A very intriguing story, didn’t know how market would react because efficacy isn’t stellar but it’s there. Definitely on my watchlist as a novel approach in oncology.

    RobertGoulet (MBIO) – Need to dig deeper there. Not sure CD123 is such a great target but valuation is cheap. The GBM response was interesting but a lot of confounding factor.

    NTLA – Agree it’s cheaper but still more than 1 year from IND and every hiccup will have a sig impact on the stock imo.

    Querebie (ESPR) – I plan on holding my shares.

    Christian (BPMC) – Yes, good drugs but valuation is quite high.

    DAn (AMBI) – Ha! That’s a nice surprise. I don’t recall the different milestones comprising the CVR but I assume that FDA/EMA approvals will account for the lion share of the amount.

    Ike (AMBI) – Thanks, where did they specify that?

    CLVS – Don’t think it has any value. Servier decided to terminate and according to the original EOS agreement they had to give rights back.


  48. “A Front Line Milestone can only be achieved if the Product’s Marketing Authorization does not require that a patient have received at least one (1) prior systemic therapy for acute myeloid leukemia (‘AML’). In addition, pursuant to the CVR Agreement, each CVR holder will be entitled to receive $2.25 per CVR upon the achievement of the First Commercial Sale (as defined below) in the United States of America following Marketing Authorization of the Product for the treatment of relapsed or refractory FMS-like tyrosine kinase 3-positive (‘FLT3-positive’) AML in patients who have received at least one prior systemic therapy for AML (the ‘Second Line Milestone’ and together, with the Front Line Milestone, the ‘Milestones’ and each a ‘Milestone’).”

  49. hey Ohad,

    Have you reviewed the Esketamine results? How do you think these bode for companies such as AGN and VTGN?

    However, drugs for AGN and VTGN work slightly differently than Esketamine; both are glycine-b antagonists (Rapastinel a partial antagonist), and are expected to work slightly differently., rehabs with better safety profile. An additional distinction for av-101 (VTGN) is that it has a longer half-life than Rapastinel.

    Another company flying under the radar is Relmada (RLMD) which is developing an oral version of Esketamine: D-methadone (with longer half-life, perhaps better potency) (D-enantiomer of ketamine). RLMD is about to start a phase 2 trial which will be led by Maurizio Fava of Harvard University (interestingly, he is also the Lead investigator for av-101)


  50. Hi Ohad,

    Any thoughts on QURE? 3 GT programs, Huntington disease, BMY partnering. Multiplied 6 fold over 52 weeks. Just did a public offering at $28 and is at that price now.

  51. hi Ohad

    I know you are not (yet) a big fan of bispecifics, though would like to ask you opinion on MGNX Macrogenics.

    the pipe is pretty huge, their cashburn also….
    they achieve favorable conditions for partnered programs, e.g. a few months ago a whopping 150 mio. USD upfront from Incyte for their PD1 mab (that late to the party).

    market cap is now at least somewhat lower (around 900 mio USD, thereof approx 350 mio. cash)

    myself I prefer companies like XNCR, PIRS, ZYME in this area; on the other hand MGNX has a lot going on…. quite some shots on goal

  52. Hi Ohad, Chris,

    Yes nice call Ohad on EXEL/Roche… sad that I did not heed it. Any thoughts on where EXEL goes from here… any upside at all in the near term? Except for global growth on sales of their winners.

  53. Paul, Just FYI, Ohad had responded to Andre’s query on OMER in the posts that followed his last piece around CNS. OMER had dipped due to Omidria reimbursement issues at that time… Nice pop today. Will be nice to see Ohad’s views based on the restoration of reimbursement for 2 years which will enable finance OMERs pipeline development.

  54. “FDA Commissioner expects gene therapy to become a ‘backbone’ treatment as antibodies are now”
    FDA to publish new guidelines for endpoints supporting accelerated appproval for GT

    Nice call Ohad!
    You saw that coming since 2 years.

  55. Interesting article
     May 4. pii: S0968-0004(18)30075-6. doi: 10.1016/j.tibs.2018.04.003. [Epub ahead of print]
    “Emerging Paradigm of Intracellular Targeting of G Protein-Coupled Receptors.”
    It looks that OMER is well positioned with the largest library of ‘unlocked’ GPCR.
    Unfortunately not a bargain as it was a month or so ago.

  56. STML

    Can you give a Short Update and what do you Expect at ASCO 2018?

    Thanks for your work Ohad!

  57. Re STML

    How do you estimate potential Revenues from SL401?

    The MC is about 470 Mill. And Seems Sports Right now.

  58. Hey Ohad,

    Have you ever looked into Israeli biotech CANF? Their ph2s A3 receptor drugs are targeting cancer and inflammation (NASH). They seem to be on the forefront of research on A3 receptor. One scientific paper (However, one of the authors is the CEO of CANF) stats the following:
    “A3AR is suggested as a specific and unique therapeutic target to combat proliferative diseases including inflammation and cancer. The excellent safety profile of A3AR agonists, currently tested in human clinical studies, is attributed to the different protective effects mediated via the receptor. The A3AR has also been identified as a biological marker to predict a patient‘s eligibility for treatment with the agonists. Taken together, the utilization of A3AR as both a biological predictive marker and a therapeutic target encompass the a ‘personalized medicine’ approach and make A3AR agonists promising small molecule drug candidates.”

  59. Regarding the Adenosine Receptor, JUNO acquired RedoxTherapies in 2016 for its A2a antagonist (for immune oncology). And CRVS is also pursuing molecules targeting the same pathway (A2a). What is your take on this target?

  60. Ike (AMBI) – Thanks.

    DAn (AGN/VTGN) – Not a big CNS expert but esketamine’s data look good (not stellar), safety issues exist but should allow approval with the right label. Hard to say about AGN’s and VTGN’s as their MOA is still quite different and don’t think we can lump them with ketamine as “NMDA antagonists” (not sure anybdy really knows how any of these drugs really work, so many interpreations…). Differentiation in side effects will be paramount.

    Don’t know RLMD, will check.

    Les (QURE) – It’s hard to justify valuation solely based on the HepB program where they did a brilliant maneuver but still no data. The Huntington program looks differentiated but not sure it’s a good thing (miRNA, direct brain injection, AAV5), I prefer to go with something along the lines of the IONS/Roche program (antisense, intrathecal) and with AAV9.

    Christian (MGNX) – Agree company and pipeline are massive but still struggling to justify valuation without a program with a clear route to market and compelling data. The PD1 deal is indeed very impressive, didn’t think PD1 mAbs would still command such a price.

    Les (EXEL) – Hard to see anything beyond cabo in RCC and HCC launch. It’s a great drug, just wondering how big the commercial potential is.

    paul (OMER) – I liked their MASP2 program but not sure how it’s doing.

    Gene (FGEN) – Too expensive (4B) IMO. Good drugs, I like the CTGF antibody.

    Andre – Thanks. Now all we need as data… 😉
    Re OMER’s GPCR platform, it has been out there for a long time, was under the impression they are not allocating a lot of resources to it.

    Biocest (STML) – Still not sure what they’ll present. Hard to find benchmarks for BPDCN, probably a modest market (100-200M per year) as chronic treatment is an issue.

    DAn (CANF) – Don’t know their programs. Adenosine modulators are very risky IMO, especially after IDO…


  61. Re STML

    Thanks. So if you assume this very limited market potential there wont be that much upside left for the stock to Go, Right? What Kind of move do you expect by Approval of SL401?

  62. Thanks for the reply, Ohad!
    I just listened to the XENE CC and looking forward to the ELIAt presentations. The CEO also spent some time on 007, claiming that a barrier to entry for competitors would be that they’d have to go through all the preclinical and toxicology etc work on from scratch, whereas XENE has inlincensed the entire research package and might be able to move the candidate straight to ph2.

  63. hi Ohad, if FGEN is too expensive, AKBA might be interesting at the current level? MC 593 mio, cash level (reach into 2020) 393 mio. doesn’t seem like a lot to me, given they have a strong development partner (Otsuka) and strong marketing partner (Fresenius/Vifor).

    FGENs recent delay of about half a year should enable AKBA to close the time gap to a good extent.

  64. Good morning Ohad.
    Xene clinical data looks impressive on 1101. Robust clinical effect on TMS with 20 mg dosing. More targeted drug in modulating the validated channel potentially best in class over older generation AED. Hopefully no dimerization.
    Like the chances for both AEDs in clinic.

  65. hello Ohad,

    is KURA still a buy from you at current level? It came down somewhat from the loftier regions, and maybe the small consolidation is finished here at 16 bucks….. (MC 527mio. USD as of now)

    Thanks as always!

  66. Rgnx

    Seems quite expensive After the recent run up. Do you still recommend buying the stock at currentLevels?

  67. Hey biohero,
    RGNX went up a lot, however AVXS license is expected to bring up to $200M annual revenue, and cash position has been improved. AVXS buyout is also huge validation of technogy platform. But cos like AGTC, and even NITE, I suppose, are undervalued.

  68. Hi Ohad,
    GEMP spiked big time today at 10 times volume and then dropped back. Looks like someone got in aggressively. They are due to announce next steps on their – similar to ESPR – trials. Have you had a chance to look at them yet? Will value your opinion. (I’m invested already but a little under water so considering adding to my position). Will appreciate opinions from others well 😊).

  69. Hi Ohad,

    how do you interpret the XENE P1 data? Is it meaningful?

    market cap still low despite the recent run…..

  70. Ohad
    Your take on the BOLD data today?
    Look good but the market did not respond.

    Interesting SA article – summary of manufacturing capabilities of the GT companies.
    BOLD, AVXS, ONCE, QURE with full operational facilities,
    BLUE, ABEO, RGNX, SGMO in process to have them operational by 2020
    Any info about NITE, KRYS, ADVM AGTC?

  71. Ohad,

    I think you have never written about DVAX Dynavax here. You like TLR9 as target? any opinion on DVAX?

    What about the target TGFb and investment ideas in this area?

  72. Russe9, my comment on LOXO:

    LOXO $ 5.04 billion
    ARRY $ 3.28 billion


    2 hits, impressive imo

  73. Hi Ohad, I wonder why Qure and Rckt are not in your GT basket. Do you have favorite pinion to get into these 2 stocks. Thanks!


  74. Hey Ohad,
    Any opinions on ARGX and XLRN? Do you think XLRN molecules could be used in combination with PDL-1 therapeutics? Or that new molecules would have to be developed?


  75. Hi
    Is it still good time to buy VKTX and ABEO?
    When will be your next update?

    ARQL is doing very good lately, any comments?

  76. Ohad
    did you have a chance to look into ALBO?

    They just started P3 in PFIC. The trail is only 24 weeks and has very reasonable primary endpoints. Strange that they are different for FDA and EMA though.
    A lot of cash (~200M), EV only 170M
    It might compliment your basket of liver stocks – MDGL and VKTX !?!

  77. XENE

    you mentioned that you’re planning to comment on the company in the near future. When can we expect your update? Thanks!!

  78. Hey Ohad,
    Any opinions on GTXI? They are developing a SARM for SUI, which seems like a huge indication. In the last CC, the VKTX CEO mentioned that potential partners, interested in VK5211, have expressed an interest in going after various indications (in addition to hip fracture), including SUI. Additionally, new studies seem to show that the effects/benefits of SARMs are long-term and sustained even after discontinuation.
    GTXI market cap is $410M.

  79. Haribo,

    XENE mentioned in the latest call that they do have discussion on the way, and that interest is coming from several parties. They might partner 1 of the 2 compounds, but it will depend on deal terms and other factors…

    I think that they are thinking about partnering is new – but sure they need to find a way to finance the 2 programs….

    I added some more after the P1 results. If one of the two drugs works, this could get considerable given current market cap < 100 mio.

  80. Hi Ohad

    Are you familiar with Revance and there competitive threat to Botox.The trials to date have shown a longer time between injections compared to Botox.How hard will it be,if approved, for RVNC to compete with such a strong franchise, and do you have a opinion from a investment standpoint given there current 1b market cap in what is a large potential market.

  81. Ohad
    You said: “Now all we need is data…”
    FCSC just delivered a nice set of data. Any plans to add them to the GT portfolio? It is (still) not expensive – almost zero EV.

  82. Hey Ohad,
    Seems that the market is nervous about ESPR ahead of impending ph3 results. Down 10% today. Do you think there the ph3 results between now and end of August (if positive and with clean safety profile) will serve as catalyst to a climb n share price? Some seem to think that this i is unlikely since every trial reading between now and September is much smaller that the one that just read (with death imbalances).
    Thanks for sharing your perspective.

  83. @Dave RVNC – Points to consider: Myobloc and Dysport already compete(d) with Botox. At least in the older botulinum toxin version. How is RVNC’s current formulation differentiated from Myobloc and Dysport’s? Is RVNC’s version “equivalent to” Allergan’s current recombinant human albumin version, or is it competing against Allergan’s older human serum albumin version? I don’t read RVNC’s info as I don’t invest in it and I haven’t read Botox articles the past 2 years.
    The duration of response for Allergan’s Botox for certain indications is already quite long. Median was already >3 months for hyperhidrosis. Patients with 6+ months DOR weren’t uncommon.

    @Ohad: We have to think of current bio-investing like the Oscar awards? Some years the candidates are all not as strong as other more prolific years?

  84. Ohad
    Gottlieb was quoting an MIT study that predicts 40 FDA-approved gene therapy products by the end of 2022
    Do you have a list of these potential 40 drugs / diseases?
    I guess Hemophilia A & B are on the top.

  85. Hi Ohad,
    Better results from ESPR but stock dropped again. Reports that their largest shareholder B.B. Biotech increased their stake by 5.2M shares at a price of $40. Analysts indicate results in September will validate better. Will really appreciate your comments on the latest results..

  86. Ohad,
    ESPR/ Cvot results….Aside from the market reaction, there’s an interesting story developing in Cvot’s. CIRT TRIAL ( low dose methotrexate) Halted by NIH. Study group released a statement that methotrexate patients had nothing to be concerned about. Add this to the CANTOS trial results on decreased CV AE’s with another anti-inflammatory agent and two large colchicine studies in Australia that are ongoing ( with some readouts showing reduced coronary plaque on CT angiography with colchicine treatment.
    To my knowledge, pure reduction of LDL-C …even below 60 has not shown reductions in coronary plaque…( except when augmented with Zetia).
    Are these suggestive of a shift in direction away from pure LDL reduction?

  87. Hey Frank,
    Yes, I think you are right. ESPR’s CVOT trial PI even argued for this, mentioning the large study (forgot if it was NOVARTIS or SANOFI) where a drug that lower only inflammation decreased cardiovascular events. That was always an argument that ESPR was keen on making: reduced inflammation, and something they claim distinguishes their drug from PCSK9 drugs.
    The market reaction is again underwhelming and disappointing, but it is understandable given continued imbalances in AEs. However, many of the comments I have seen on the biotwitter sphere seem misplaced: they forget that the main drug for ESPR will be the Zetia combo drug, and they also seem to forget that the LDL lowering reported is on top of statin background therapy, so an additional reduction.

  88. Hi Ohad, are you familiar with Marker Therapeutics (private CAR-T company recently merged with TapImmune)? Thanks.

  89. O’Hara

    Are you familiar with MGEN. Their treatments revolve around treating various indications by microRNA modulation. Market cap seems reasonable given multiple early stage programs in several areas. In general, do you think treatment utilizing RNA to regulate gene expression can be a effective way to treat different diseases.

  90. Ohad
    TGFb dedicated company srrk had an ipo.
    No sure about the valuation (~350M) but it looks interesting. Too early to jump in??


  91. Alex (AMBI) – Not yet, triggering is after first commercial sale imo.

    Biocest (STML) – Hard to predict commercial trajectyory in BPDCN as there is no real benchmark. If you assume sales multiple of 5, there is still room for upside.

    DAn (XENE) – Personally I am less excited about that program, prefer new compounds with full patent protection and best in class profile.

    Christian (AKBA) – Could be an interesting bet on the “underdog’ even though there are reasons for the valuation gap. Don’t know the field well but the AKBA program has a checkered history.

    Jaime Allen (XENE) – Agree, good update, still preliminary as they haven’t completed the MAD portion but this is exactly what one would hope to see at this stage. More de-risked now.

    Christian (KURA) – Yes, I plan on holding it as I think it can easily double if ORR continues to look good.

    Biohero (RGNX) – Agree it isn’t cheap but exposure to many AAV9/8, including BOLD’s XLMTM program could justify a big portion of valuation. Now they need data in AMD or MPS1/2 to drive price higher. AVXS wasn’t cheap either but it’s important to have exposure to the leaders in an innovative field like GTx.

    Les (GEMP) – Even after the recent crisis, I prefer ESPR. in that field

    Christian (XENE) – I think it’s very positive, still early but the program is even more de-risked now. Agree about market cap being low, one of the cheapest names I am aware of. Will publish my take on the data soon.


  92. Andre (BOLD) – Data are still directionally positive but I was expecting a more robust effect, kinda hoping to see more stories like patient #1 but perhaps it is not realistic in older kids.

    I am pretty sure ADVM and AGTC have good manufacturing capabilities.

    Russe9 (LOXO) – Efficacy is clearly there and going with a selective compound appears to pay off but I didn’t think their data implies superiority over BPCM.

    Christian (DVAX) – Sorry don’t know them well. A lot of activity around innate immunity recently.
    TGFb – A lot of buzz around the superfamily, several private companies with novel approaches but still no clinical validation. Let’s wait to see Merck KGa’s data in HPV+ tumors.


  93. Ohad

    You have mentioned XENE as being one of the cheapest names in the bio space. Can you share other names you feel fall into that same category?

  94. Jinyu

    QURE – They made a great comeback but at these levels without clinical data from their modified product I prefer to wait for a better entry point.
    RCKT – I am following them and think they have some interesting concept like in vivo selection of transduced cells but stage and valuation are an issue imo.

    ARGX – Missed the big jump with the MG data, still following them.
    XLRN – Anxious to see their MDS data, would be great to have a new drug for MDS but valuation is high in light of CELG’s dominant share of that product. Don’t think they will develop current molecules for cancer, not sure they have the right ligand selectivity, focus today is on TGFb.

    Ruhu – I am still holding both.
    Can’t comment on ARQL.

    andre (ALBO) – Not yet sorry. PFIC sounds like an attractive indication for GTx so this is a potential threat in the long term.

    Haribo (XENE) – Just published today :)

    DAn (GTXI) – Haven’t looked at them for a while.

    Dave (RVNC) – Sorry, not familiar with the field.

    andre (FCSC) – Will check, could be an interesting hedge for ABEO.

    DAn (ESPR) – The market is rightfully nervous but after reviewing the data I find it hard to believe BA can dramatically accelerate tumor progression within several months. I think the signal is false but you never know…

    Fan (ABEO) – Not sure what triggered the selloff, perhaps the DEB data and competing data from FCSC.

    CD – I actually think that the problem is not always quality of candidates but valuations.

    Carlos (LIFE) – Not sure, haven’t been following them recently but recent changes certainly aren’t encouraging…

    andre – Haven’t seen this list. Yep, Hem A and B will probably one of the first.

    Les (ESPR) – I am still holding as I think the death imbalance is just bad luck but we don’t know for sure so the risk is obviously there.

    Frank (ESPR) – I think that experience with statins + CANTOS data clearly implicate inflammatory mediators as important for long term outcomes. In that sense, ESPR’s CRP reductions are very encouraging.

    Xavi – Don’t know them well.

    MGEN – Agree, just started following them and the fact they see activity with a systemic miRNA is quite impressive.

    Andre (SRRK) – Still not sure how differentiated their approach of targeting latent myostatin is. In any case, don’t see the urgency given stage and valuation.


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