Xenon – P1 data provide more de-risking

To me, the main challenge in today’s biotech market is finding good quality assets with attractive valuations. There are definitely a lot of promising programs out there but valuations are often hard to justify as they reflect limited development risk and unrealistic commercial potential. From a risk/reward standpoint, it is hard to get excited about valuations of >$0.5B for companies before clinical proof of concept and $2-5B for clinically validated programs.

From that perspective, Xenon (XENE) is a market anomaly, with two promising clinical stage programs, a robust discovery platform and a market cap of just under $100M. Its two epilepsy programs, XEN1101 (Kv7 opener) and XEN901 (Nav1.6 inhibitor), are still in P1 but at the current levels the upside potential is too significant to ignore.

Not the typical CNS programs

XEN1101 and XEN901 do not have the typical risk profile seen with other P1 CNS programs, they are de-risked on multiple fronts:

  • Genetic validation in humans – Mutations in Kv7.2 and Nav1.6 are associated with severe forms of epilepsy in humans
  • Pharmacologic validation in humans – There are approved anti-epileptic drugs that have overlapping MOAs with XEN1101 and XEN901
  • “Precision medicine” regulatory route – XEN1101 and XEN901 may be pursued in biomarker-defined populations which represent a fast route to market with a high likelihood of success

Selectivity and safety profile as key differentiators  

XEN1101 was designed based on clinical experience with ezogabine (Potiga), an FDA approved Kv7 opener with proven clinical efficacy that was withdrawn from the market due to safety concerns. XEN1101 is more potent and does not seem to dimerize or bind melanin (seen as the primary liability with ezogabine as it leads skin and eye pigmentation). It also has a better PK profile that should support daily dosing vs. thrice daily with ezogabine.

For XEN901, the primary differentiation from older Nav blockers lies in the selectivity towards Nav1.6, which is thought to be a primary driver of seizures. XEN901’s potency and selectivity led to a dramatically improved therapeutic window in mice (see figure below), which will hopefully translate to the clinic. According to Xenon, XEN901 is the only Nav1.6-selective molecule in development.


P1 data further provide more de-risking

Earlier this month, Xenon presented P1 data for XEN1101 and XEN901. The drugs appear safe, have a favorable PK profile, and exposure is at the predicted efficacy range at relatively low doses.

For XEN1101, there are even hints of biological activity using brain imaging tests that had been reported with ezogabine. Interestingly and with the caveat of cross-trial comparisons, XEN1101 demonstrated a stronger imaging signal than what is reported with ezogabine at 20-fold lower dose. The company plans to present imaging data for additional healthy volunteers as well as safety data for repeated dosing. Assuming no safety issues arise, an efficacy P2 is expected to start towards the end of the year.

Potential utility for XEN1101 in ALS

Kv7 is garnering attention as a target for ALS, following the launch of QurAlis, which is also developing a next-gen Kv7 opener. QurAlis’s scientific founders identified Kv7 as a potential target in patient-derived cells (published here) and used ezogabine to demonstrate their hypothesis (see figure below).  Data on QurAlis’s Kv7 opener are limited but Xenon appears to be 2-3 years ahead and could pursue ALS as a second indication.


Source: Cell Rep. 2014 Apr 10; 7(1): 1–11.

Upside potential

As a small cap biotech, Xenon comes with all the usual risks (no clinical proof of concept, long timelines, high rate of cash burn etc.) but at a valuation of $100M these are risks I am happy to take. Commercial potential for a new anti-epileptic drug with a favorable safety profile is in the $400M-$500M range, not including the orphan indications that could add additional ~$150M per indication. If safety data for XEN1101 and XEN901 continue to look clean (long term safety data is expected by YE18), it is hard for me to envision Xenon staying independent at these levels.

Portfolio updates

I am adding a third position in Xenon following the recent P1 data and the imaging signal. I am also adding Endocyte (ECYT) and selling Avexis (AVXS) following the Novartis acquisition.

Portfolio holdings – May 28, 2018

biotech portfolio - after changes - 28-5-2018

biotech etfs - 28-5-2018

156 thoughts on “Xenon – P1 data provide more de-risking

  1. Thanks Ohad, very informative as usual!.
    You left aside XEN007 for Hemiplegic Migraine. Not interesting?

    A few interesting IPO fillings I would appreciate your opinion about:
    AVRO – GT for Fabry, Gaucher, Pompe
    MGTA – cell therapy inherited metabolics & blood cancer

  2. Ohad and ALL
    Here is my list of 30+ GT drugs I keep track on. Any comment on omission, error is appreciated. It is an Excel table but formation will lost. Data from company of analyst’s presentations

    Comp. Trail. Target Pivotal Approval
    ABEO EB-101 RDEB –yes 2019
    ABEO ABO102 MPS-IIIA 2018 ? 2019
    BLUE Lenti-D CALD –yes 2019
    BLUE Lenti-Gl b-thal –yes 2019
    NITE REP1 Chloroid. –yes 2019
    VYGR AADC Parkins. –yes 2019
    ABEO ABO-101 MPS-IIIB 2019 ? 2020
    QURE AMT060 Hem-B 2019 ? 2020
    ONCE SPK9001 Hem-B 2019 ? 2020
    AVRO AVRD-01 Farby 2019? 2020
    BOLD AT132 XLMTN 2019 ? 2021
    BOLD AT342 CrNaj 2019 ? 2021
    RCKT RP-L02 FrAn 2019? 2021
    RGNX RGX-314 W-AMD 2019? 2021
    RGNX RGX-501 HoFH 2019? 2021
    RGNX RGX-111 MPS-I 2019? 2021
    BMRN BMN270 Hem-A 2019? 2021
    FCSC FCX-007 RDEB 2019? 2021
    QURE AMT-061 Hem-A 2020? 2022
    QURE AMT-130 Hunting. 2020? 2022
    SGMO SB-525 Hem-A 2019? 2022
    SGMO SB-FIX Hem-B 2019? 2022
    SGMO SB-318 MPS-I 2019? 2022
    SGMO SB-913 MPS-II 2019? 2022
    RARE DTX301 OTC-def. 2019? 2022
    RARE DTX401 GSD1A 2019? 2022
    ONCE SPK7001 Choroid. 2019? 2022
    ONCE SPK8011 Hem-A 2019? 2022
    AGTC XLRS xRS1 2019? 2022
    AGTC ACHM CNGB3 2019? 2022
    AGTC ACHM CNGB4 2019? 2022
    AGTC XLRP RPGR 2019? 2022

  3. Ohad

    ESPR.Being that you think the death imbalances were probably just bad luck, what will be the determing factor for the FDA, to either approve while the CVOT trials are still ongoing or waiting another 3+ years for those trials to complete before possibly approving their cholesterol pill.

  4. andre –

    XENE – I am less excited about that program (but also less familiar), typically prefer innovative drugs and MOAs.
    AVRO – I like them a lot, it’s about time someone does something in those LSDs to replace enzyme replacement therapy which is not optimal. The flip side is that you have an effective alternative so the bar (safety and efficacy) is set higher.
    EIDX – Don’t know them well.
    MGTA – Sounds like a unique approach to revitalize a field that hasn’t seen a lot of innovation. Need to learn more there.

    Thanks for sharing the list, very nice.

    Dave (ESPR) – That’s a good question as I don’t think the FDA will take any chances with this type of drug if there are troubling signals. I guess long term follow up and data from additional studies will help to demonstrate that mortality is balancing out, we’ll see later this year…


  5. Hi Ohad, any thoughts behind your ecyt buy? Any comments on arql at the current valuation? I was also looking at Xene if it works for tinnitus as an offlabel? The market is huge. Thank you

  6. Any thoughts on (prqr)proqr? The valuation and pipeline seems attractive. Thanks

  7. hey Ohad
    thanks for this new post and the replies to the questions.
    I had already added some XENE to my position given the recent results, low market cup, and your insight into the two compounds and how they are partly derisked.
    Have you ever looked at MTFB? They are submitting to the FDA the ph3 for their antibiotic for bacterial infections. Market cap is low ($120M) and the distinguishing factor or their drug is that it is safer than standard of care vancomycin (safe clearance through kidneys). It seems that 20-30% of vancomycin users have kidney AEs.
    It seems the company is poised for a partnership or buyout.
    Additionally, any opinions on TRIL, also in light of results by DC47 competing companies?

  8. ECYT

    The stock Climbed up nicely in the past. You are still optimistic about further upside – can you explain why and How do you estimate the Potential market for their lead drug? Thank you!

  9. FMI – what do you think the chances that it will be acquired?
    AGTC – Speaking of cheap, Is it still attractive?

  10. Hey Ohad
    any opinions on the TPIV merger with MarkerTx out of Baylor College? They claim that Marker’s carT tech is more scalable, and 1/10th the cost of KITE’s carTs (to produce), while also targeting multi TAA. Additional benefits, though size of trial to date is only 60 patients, are more durable responses and no grade III AEs. Market cap of combined companies is $50M. Went up15% today on WBB securities buy (from speculative buy). Merger was finalized days ago and company will rename itself and move to Houston, TX.

  11. Michael (ECYT) – Their Lancet Oncology publication caught me by surprise, was not aware of this program and data look very compelling, especially the response rate in soft tissue lesions, in contrast to Xofigo which affects only bone mets.

    XENE – Not familiar with tinnitus as an indication for their compounds.
    ARQL – Can’t discuss, sorry.

    Michael (PRQR) – Haven’t looked at them for a while, still not sure how their drugs work and the CF data were quite preliiminary from what I recall.

    MFTB – In antibiotics I prefer to focus on novel drugs with new MOAs as it will always be hard to compete with cheap generic antibiotics. What the world needs is innovative drugs against multi-drug resistant infections, not just a slightly better safety profile.
    TRIL – So far CD47 is a disappointment just like all other checkpoint inhibitors, hope that changes…

    Gandalf (ECYT) – I think a radioactive injectable will never be as big as Xtandi or Zytiga but it can definitely reach 1B in sales even as 2nd line treatment (before chemo).

    Alex –
    FMI – Honestly speaking it is hard to figure out what is going there with the stock price approaching $100.
    AGTC – I plan on holding, hoping for clinical catalysts next year.


  12. What about TPIV?
    Thanks; makes sense re antibiotics- CFRX and APHB are the two in my portfolio with new MOA (phage end lysins). Ph2 results for CFRX in next 6 months.

  13. What’s up with AGTC doing a S3 filing? Why do they need to raise cash thru offering in near future ? They have nice cash and 0 debt? Thanks

  14. DAn –
    Don’t know TPIV, With respect to the two others, I would prefer classic small molecules as phages and lysins may be challenging.

    Luigi (AGTC) – Agree, don’t see the need raise cash.

    Alex (MDGL/VKTX) – Thanks. Good data, important validation of non-invasive imaging. Placebo arm did quite well…


  15. Hi Ohad,

    Great news and congrats on MDGL/VKTX. Had two queries – VKTX’s drug apparently has a similar action to MDGL’s and an additional target but does its success follow automatically? Also I remember that ICPT jumped all the way to the mid 400’s on similar news but came back to earth due to later results… are there any such risks with MDGL?

  16. Nice call on both MDGL and VKTX.!!
    Somebody has to run a trail comparing placebo to nothing and make the placebo an approval-able drug. FDA will go for it with such good data
    Placebo had 32% NAS decrease of 2 points and 23% decrease in fibrosis!!!
    Anyone of the NASH companies would be happy to show such performance.
    Nice data in LDL-C reduction as well – 28.5% reduction in pts which do not tolerate statin.
    Interesting that ESPR is up on that new?!?

  17. Les (MDGL/VKTX) – Thanks. This is clearly the best NASH data set I have seen to date. Not perfect but clearly in the right direction.
    VKTX’s VK2809 also targets thyroid beta so it belongs to the same class but the molecules are different, have a different selectivity profile and so far VKTX’s data contained some safety signals that have not been observed with MDGL (different populations, cross trial comparisons etc.). So success is definitely not automatic. Similar case to SAGE/MRNS.
    Yes, the risk of seeing a significant pullback in MDGL is very real, a lot depends on long term safety profile, which is still an open question and many people are nervous about chronic activation of thyroid receptor.

    andre (MDGL/VKTX) – Thanks. Indeed, placebo is a very effective drug. I suspect that lifestyle changes are behind a lot of this change. I agree, good LDL activity and I am also surprised ESPR went up yesterday. We need to remember that MDGL is still a long way from approval and not sure whether they will actually pursue classic LDL reductions but definitely a threat to ESPR. ESPR’s two main advantages in the effect on CRP and the larger safety database.

    Sam (ICPT) – I prefer other NASH drugs like MDGL/VKTX. Even with FXR agonists there might be better, more potent and selective drugs in development.


  18. Hey Ohad,
    Where do you see your portfolio going in the next 6-12 months? I wonder your take on the big picture and the overall sentiment (for the portfolio). It seems that stocks such as XENE and the GTx stocks have significant margins for growth, and you were saying KURA could potentially double.

  19. Hi Ohad,

    Thanks much for your responses.
    Saw another article to add to your great analysis of XENE (although different conclusion I.e. relook at it later in the year seemingly based on assumption that there will be better entry points due to the ATM share sales).

    Of course people often wait for too long :-).

  20. Hi Ohad,

    Regarding valuation of MDGL. It stands at around $3.9B. At its peak ICPT went all the way up to around $12B. Room for MDGL to double at least?

  21. Ohad
    could you please comment on the ZYME data
    Good activity for a single agent. In breast cancer they had 50% DCR (PR+SD). 4 more also responded, bringing the DCR to 72%, but they had CNS metastasis and were considered Progressed. Is there any drug that can be used as a combo to prevent that? ZW25 was very safe (only Gr1 and 2) so the combo looks visible.

  22. Hey Ohad,

    what do you think of Genmab? I know you sold the stock 2 (?) years ago. Stock has fallen sharply after they stopped the Darzalex-Anti-PD-(L)1-Study. They are now more than 30% away from their ATH last year. Do you see this as a good entry point? And how do you feel about their early stage pipeline?

    Thanks for sharing your thoughts.


  23. Ohad, Andre,

    regarding ZYME, it is now already in the part 3 of Phase 1 where combination cohorts with chemo are being tested:
    – Paclitaxel
    – Capecitabine
    – Vinorelbin

    I am not familiar with these chemo-regimens in HER2 expressing cancers, but Ohad, what’s your general thought on these combinations? (side effects profile, efficacy,…)

    What other combination agents would be an option?

    Does the considerable drop in RR for the breast cancer patients worry you?

    The data for the Daiichi Sankyo ADC DS8201 seem very strong, but safety not comparable at all to ZW25 either

    Do you see room for both?

    ZW25 seems to be an excellent backbone for an ADC. let’s hope ZW49 will move along fast and that Kairos ADC-tech is not a dud.

  24. Hi Ohad

    can you please share some thoughts about cellular anti-cancer therapy? Namely what approach do you think will eventually win – allogenic (Cellectis, Allogene) vs autologous (JUNO KITE). What technology/firm has the highest chance to crack tough solid tumors? And lastly do you have some favorite stocks in this field? Maybe some overlooked underdogs? :-)

    Thank you again for your terrific blog and have a nice weekend. Milos

  25. Christian,
    I guess the safety issues with DS8201 was the reason Daiichi signed a collaboration with ZYME.
    About brain metastasis, I remember CASC had TKI inhibitor, which was working well against that. SGEN bought them, but probable something else is available for a combo. I don’t believe chemo would help.
    ZW49 may also not help since is the same as ZW25 but with payload.

    I am a bit puzzled by the bb2121 data. They reported 11.8 months PFS and many on bio-twitter say is not good enough and bb2121 is not a real cure.
    But they got 50% CR in the high doses. So 50% of the patients are happy and cured. How this “low” PFS and high CR come mathematically / statistically together.

  26. Hi Ohad,
    LOXO and Blueprint have been in the news recently. Your thoughts on RET and any early stage companies for your GT basket?

  27. Hi Ohad

    Re the imbalance of deaths in Esperion’s Study 1 … doesn’t the continuation of the CVOT answer that question? BTW thank you for the blog … I really enjoy it … best regards, Mike

  28. Ohad
    A few more IPO coming soon, I would appreciate your opinion about:

    APTX – Ph2 with selective NMDAr modulator for chronic pain. A collaboration with AGN with a drag from the same class for Major Depression Disorder may validate the platform

    MGTX – GT with 3 Ph1 in ophthalmology, one Ph1/2 in xerostomia; + preclinical in CNS (ALS, Alzheimer’s) . Potential 380M cap at IPO price

    KZR – 2 Ph 1b and 4 Ph 1a in several autoimmune diseases. They claim ” first-in-class selective immuno – proteasome inhibitor”. The lead trail is in systemic lupus, which probably a bit risky, but the platform in general looks interesting

  29. Ohad

    The NKTR/BMY data set in melanoma and kidney cancer showed a lesser response as more patients were added. They point to the fact that these responses with improve over time as it was early in treatment, and that the ORR increased to over 70% from a previous 46%. How would you interpret this data, in light of the fact that the PD-L1 negative responses were about 50% which is quite impressive. I guess time will tell, but do you think the expected negative reaction is warranted.

  30. Ohad,

    Thanks as always for the blog. I appreciate your effort. Is there any comment on ZYME? Anyone? Sorry I just don’t understand the negative reaction? Am I missing something?

    Best regards,


  31. DAn – I wish I knew….. 😉

    Les (MDGL) – This is the point in which every estimate is very speculative as NASH still doesn’t exist as a commercial indication. A lot of open questions but a conservative scenario can easily get us to $1B in sales.

    andre (ZYME) – Efficacy signals are still there, nice to see more responses in gastric cancer, but durability continues to look a little weak. Daiichi’s ADC looks more potent but ZYME has a much better safety profile so combination regimens are more straightforward.

    Martin (Genmab) – I was surprised the market had so much hope for the PD1 combination programs, I always view it as a wild card. Their pipeline is still early , the AXL program looks intersting but nothing I would put in models for now.

    Christian (ZYME) – I think it’s the right way forward with a well tolerated agent. Curious to see combination studies with other HER2 agents (in cases where there is no direct competition). I certainly don’t think te drop in RR is a good sign but even after the drop efficacy is there.

    Yes, there is room for both but at least in late lines it might be a zero sum game.

    Milos – Unfortunately there is not a lot I can say, Pontifax is invested in two companies that are developing adoptive cell transfer (including allogeneic) so prefer not to discuss.

    andre (BLUE) – I thought data were still quite strong in this population. The discrepancy between the high CR rate and the PFS figure can be explained by relapses after seveeral months of remission.

    Les (LOXO/BPMC) – LOXO’s data were great, numerically superior to BPMC but hard to compare at this stage.

    Mike Iles (ESPR) – Thanks. I guess they have periodical safety monitoring reviews but not sure how they look at the data on an ongoing basis.


    APTX – Interesting to see NMDA drug for pain, not familiar with the program.

    MGTX – I like the xerostomia program, pretty cool approach but no data wit the new vector.

    KZR – Good biology, need to learn more about them.

    Dave (NKTR/BMY) – Yes, I think the reaction is more than justified. I have serious doubts about NKTR and ARMO, looks like IDO all over again.

    Peter (ZYME) – There is simply a drug for the same population with better efficacy. ZYME has the upper hand safety-wise but response rate in breast cancer is lower than previous update.


  32. Thanks!
    What are your thoughts on Forty 7 IPO and the results they are boasting? Another IDO?

  33. What 2018 IPOs are you interested in and why? Ignoring for now the valuation since biotech IPOs of recent years always open at ridiculously high valuations…

  34. re 47
    endpts.com, in a recent article, calls the results “impressive initial snapshot.”

  35. DAn – It’s another IDO because they have some monotherapy activity (limited and preliminary of course…). The Rituxan combination data is hard to assess as a single arm study. Not sure I would call them “impressive” but at least they have a signal. In any case, valuation will probably be too high given stage of development.

    Kay Lee – I don’t have a particular IPO I am following. Obviously, GTx companies are of interest.


  36. Hi Ohad
    What do you think about the result that publish in NERV ?


  37. Ohad
    About KZR – in S1 they wrote that MOA is validates with data from Velcade and Kyprolis. But they can’t be used long term due to side effects. KZR-616 does not have the same AE because is selective proteasome inhibitors. If it works in all autoimmune cases for which they have positive data with Vercade – it would be enormous!
    In Ph 1a they had only Gr1 and 2 AE but no one typically associated with Velcade, which somehow validates their main point. They said that they may start directly registration trails in multiple indication after Ph 1.
    What do you think about the above claims, do they make sense and how easy is to get 616 approved as a basket case for a bunch of AI diseases, like LOXO did in TRK fusion.

  38. Hi Ohad,

    What are thoughts on MEIPs PIKdelta? Bringing Dan’s question into the mix, I realize there are LOT of competitors in the delta space and (BAD/POORLY adopted drugs to show for it) but the efficacy seems interesting in light of ~125mm cap and 30 to 40 mm in cash. Any thoughts about this or TGTX delta in light of Imburvica/Calquence/Ventoclax and other emerging or approved B cell agents?


  39. Hi Ohad,

    GNMX has 2 catalysts approaching , any opinion on their programs?


  40. Can anyone tell me why a company like Mirati would issue some prepaid warrants rather than all common stock in their most recent underwriting.


  41. Private placement to NEA has TPIV soaring 80%. What a deal for NEA, they buy in at $4 and overnight they double their money.

  42. Ohad

    ENTA.You have mentioned ICPT in the past and said there may be better FXR agonists out there. Are you familiar with EDP-205 from ENTA.The company has done extremely well with their Hep C drug Mayvret with Abbvie and I rarely hear them talked about with there NASH drug. The stock is up 500+% over last 5 years and receives royalties on Mayret sales. Do you think the 2+ billion mkt cap is fair value and do you see potential in there NASH program.

  43. JACK (NERV) – Not familiar of any meaningful new data. The recent publication contains data which have already been reported.

    andre (KZR) – Targeting the immuno-proteasome makes sense and could be relevant for many autoimmune diseases. Agree the drug appears safer than Velcade but data are still limited. I don’t think they can get it approved in a basket study like in oncology, must have a placebo controlled study (expected by mid 2020 for lupus nephritis).

    DAn (TGTX) – IMO no.

    Mike Witzmann (MEIP) – As you stated, there is a lot of competition and I am still not aware of any meaningful clinical differentiation.

    John (GNMX) – Haven’t been following them for a while, sorry…

    john (MRTX) – Strange… very uncommon in these situations.

    DAn (TPIV) – Still needs to eventually work in the clinic….


  44. Have you looked at israeli company GLMD?
    up 200% on ph2 NASH. What distinquishes their compound its the clean safety profile, with bodes well for combination treatment of NASH. Results otherwise are not too impressive. Market cap is now $400M, I believe…

  45. Ohad
    APTX presentation is available now on RetailRoadShow. Their approach looks validated – to modulate NMDA receptors. More than 20 potential indications, but they start with just 3.

    The experiments for memory recovery (short and long memory) in Parkinson is very impressive. Still pre-clinical in monkeys, but the results were shocking (to me). Not sure I understood how modulating NMDArs can overcome the dopamine depletion. And that’s after single administration of the drug?!?
    Any comment about that? Or just too early to be excited……

  46. Re GLMD
    reduction of fibrosis is equal to MDGL; both at 29%. However placebo in $GLMD’s study is 17% vs 23% for MDGL.

  47. While you’re looking at APTX/NMDA modulation…can you add a review of VTGN and their AV 101. Tiny market cap in a space that’s getting attention.

  48. Hey Ohad,
    I have seen a lot of criticism on Twitter of GLMD results; however it seems that the patient population they treated was much broader and less sick than MDGL. Moreover this was a global study across various continets, and supposedly variability of NASH phenotype makes it more challenging to get positive results. Finally, the drug greatly reduced ALT and has a cleaner safety profile than placebo, which, I wonder, might leave some room for increasing the dose? (So far the study has shown dose dependent reductions)
    What is your take? Do you agree that MDGL has conducted a fantastically well-executed study to limit AE risks and guarantee highest possible outcomes? But it remains to be seen how their drug will fare in reality, especially with regards with safety.
    Thanks for your perspective!

  49. Hey Ohad,

    KPTI is one of the few cos that has gone up in value after EHA. What do you think of the prospects for their drug?

  50. Wow what a journey Roche is buying the rest of the FMI for $135 per share….congrats Ohad

  51. FMI – now we know why the stock price was moving up and up and up.
    The chart looks the same as AVXS in the last 6 months – go figure why :)

    NTGN – IPO on June 27. The presentation is on RetailRoadShow. They seam to have a very strong clinical prove of principle. Wonder why GNCA is moving so slow

  52. Congrats one more time Ohad, you have done it again with FMI!

    Have you had a chance to relook at GEMP?

  53. Thanks as always for your analysis and insights, Ohad — very much appreciated. Congratulations on FMI!

  54. Ohad

    You recently said you just started following MGEN and were impressed that they were seeing activity with a systemic miRNA. Understanding that you are finding it harder to find biotech companies with sensible valuations, what would it take to start a position in MGEN which seems to have a relatively modest valuation of less than 300M.

  55. Good morning Ohad. Just to piggyback off of Andre’s inquiry Re: NTGN. I know you are not a fan of the vaccine approach however Neoantigens have obtained excellent CRs added to checkpoints in Melanoma. vaccine cocktail with the individual’s tumor specific neoantigen genome. Durability with this approach should be excellent. thoughts?

  56. Hi Ohad, Any thoughts on MGTX (recent IPO), gene therapy play, 4 programs in clinic, reasonable market cap (< $400 M). thanks. Steve

  57. FATE

    nice technology with their ProTmune platform. do you have an opinion? maybe its too early to get in?


    do you like the immunotherapy programs? MRTX looks expensive. ADRO with nice partnerships (Novartis, Merck) and reasonable valuation, although they’re in P1.


  58. Hello Ohad,
    Any opinions on MGEN, and specifically their miR-155 inhibitor?
    New research linking Alzheimer’s to viruses also points to how depletion of Mir155 (in mice) causes greater accumulation of amyloid plaques. It seems that their inhibitor has many shots on goals and could be applicable to many diseases.
    I just started a position in MGEN.

  59. Hi all
    I updated the GT table with a column for RMAT designation
    Comp.; Trail; Indication; RMAT; Pivotal; Approval
    ABEO; EB-101; RDEB; yes; yes; 2019
    ABEO; ABO-102; MPS IIIA; yes, 2018; 2019
    BLUE; Lenti-D; CALD; yes; yes; 2019
    BLUE; Lenti-Gl; b-thal ; yes; yes; 2019
    NITE; NSR-REP1; Chloroid.; yes; yes; 2019
    VYGR; VY-AADC; Parkinson; yes; yes; 2019

    All other GTs in the previous table do not have RMAT

  60. Ohad what do you think of the recent $mgtx ipo? valid company with tech and facilities or classic cash burner ?

  61. DAn (GLMD) – Not a NASH expert but from what I understand there were some red flags in the data set and how data were analyzed. Haven’t delved into the data but the overall feedback from serious people is disconcerting.

    andre (APTX) – I am having a hard time buying into the concept of MNDA antagonists for pain and other conditions.

    Frank (VTGN) – Agree the field is getting more attention, let’s see how Esketamine’s launch goes.

    Kenny (KALA) – Sorry, don’t know them well.

    DAn (KPTI) – It’s a bit of a head-scratcher for me… the drug falls somewhere in between in terms of clinical efficacy as monotherapy and valuation is already >1B. Perhaps in combination as it has a completely different MOA.

    Dan G. (FMI) – Thanks. Indeed quite a jouney… proving again that sometimes all you need to do is nothing (if you have a 4-5 year horizon).

    Andre (FMI) – Yep…

    NTGN – I have high hopes for neo-epitopes but not a big fan of vaccines. Glad to see they have a T cell therapy program.

    Les (FMI) – Thanks.
    GEMP – I still prefer ESPR and based on the FMI experience maybe now is the time to add.

    Debra – Thanks!

    Dave (MGEN) – Agree, valuation is reasonable (not cheap), I need to find time and delve deeper.

    Jaime Allen (NTGN) – Hope I am wrong but I don’t think those vaccines do anything, the IDO failure and NKTR’s recent data show how those single arm studies are very hard to interpret.

    Mike (MRUS) – Technology is very efficient but bispecifics is still an area looking for a breakthrough.

    Steve (MGTX) – Agree, a diversified GTx play and valuation isn’t very high.

    Haribo (FATE) – Sorry, don’t know them well.
    ADRO – Still waiting to see STING data.
    MRTX – Too expensive IMO, data aren’t that compelling to me.

    DAn (MGEN) – I think it would be challenging to extrapolate beyond the current data in T cell lymphoma to additional indications. This is true especially in CNS indications.

    andre – Thanks for the update!

    RobertGoulet (FCSC) – Still didn’t have a chance to review…


  62. Sarepta micro-dystrophin gene therapy required very high amounts of vector genome…(up to 10^14vg/kg, with dose-escalation plan dose of 2×10^14vg/kg; in a DMD child that is equivalent to 8×10^15 AAV vector genomes.
    Do these enormous quantities:
    1: Favor ONCE as a takeout candidate since they have shown effective signals at 20-30 X’s lower genome amounts.
    2: Favor Gene Therapy Companies that have demonstrated cost effective manufacturing of the AAV vector genomes. If so, which companies?

  63. Ohad

    RGNX has exploded higher since AVXS was bought out by Novartis for close to 9 billion. At the time you thought it was a hefty price to pay. With RGNX trading at a 2.4 billion valuation, if they were to be purchased, at what price would you estimate they could fetch, given that they seem to have possession of a widely adopted NAV technology platform that is partnered with many companies including AVXS.

  64. Ohad

    Kura just announced a secondary offering to further fund there phase III registration trials that are about to begin on tipifarnib in head and neck cancer as well as there other programs.If I remember you seemed to be more excited with what is a still extremely early KOL-539 program. With a valuation close to 600M do you still view KURA as having a reasonable valuation, or would you rather wait to see how tipifarnib plays out before considering purchasing additional shares.

  65. Update to the GT table following the QURE news today:
    Comp.; Trail; Indication; RMAT/BTD; Pivotal; Approval
    QURE; AMT-061; Hem-B; yes; yes; 2020

  66. OVID / NERV

    Which stock do you Prefer? Nerv is already in p3 with one drug. Both stocks are Not priced very high

  67. hey Ohad
    nicely written press release by GEMP regarding ph2 results. What do you think of their chances? They are trying to pivot into NASH.
    Thanks for sharing you perspective,

  68. Hi Ohad,
    You had indicated you still prefer ESPR to GEMP in response to my query of a few days ago. Given their most recent release your thoughts? Of course phase 3 can have similar issues as ESPR but GEMP will tread more cautiously given ESPR experiences.

    XENE volume $2M+ today vs 230K 10-day average… something seems to be brewing – catalysts are supposed to be in the last quarter? Wonder what’s driving this volume.

  69. Ohad

    Can you share any thoughts you may have on Pieris Pharmaceuticals and there proprietary Anticalin based therapeutics for several indications especially immunotherapy. Most of there programs are pre clinical or Phase 1, but their collaborations are with several large Pharma companies. Mkt cap 270 with 150 tells me they are not giving much value to there technology.

  70. Ohad. As always thanks for your support. Recent big buys in XENE with increased volume. What do you see as a BO price target with current assets and further validation?

  71. Hi Ohad

    What are some stocks from your portfolio that I can still buy now, if i am starting new position.

  72. Recent 8K filing from XENE:
    “On May 8, 2018, Xenon Pharmaceuticals Inc. (the “Company”) entered into an at-the-market equity offering sales agreement (the “Sales Agreement”) with Stifel, Nicolaus & Company, Incorporated (“Stifel”) to sell common shares of the Company having aggregate sales proceeds of up to $30.0 million, from time to time, through an “at the market” equity offering program under which Stifel will act as sales agent. As of July 3, 2018, the Company has sold 3,440,000 common shares for proceeds of approximately $29.2 million, net of commissions paid.”

    This may represent all of the large block trades that have recently occurred.
    Ohad…..How do you interpret this move?

  73. Hi Ohad
    do you have an opinion on TRVN’s TRV250 for acute migraine?
    any reason not to sell FMI?


  74. ohad

    are you familiar with ZSAN. They have a treatment for migraines, M207 that they believe gives faster relief to migraine sufferers. It is delivered through a adhesive patch that delivers the drug quickly thru the skin. Is there any color you can add regarding this company.

  75. Hey Ohad,
    One more question for you, thanks.

    Have you had a chance to look at CAPR? Valuation is back down (shares more than halved since the high of last year).
    They are progressing two programs with exosomes derived from cardiospheres as the MOA. The exosomes have anti-inflammatory properties and contain beneficial miRs (miR-146a, -148a, -151, -409, -423) that are also immunomodulatory. In the ph2 trial they’re treating 90 DMD patients with 4 intravenous systemic infusion (at 1, 3, 6, 9, and 12 months) which is a change from previous trial ( one coronary fusion) and is a risk factor, but seems based on the new knowledge that exosomes and miRs are what provides the healing, not the stem cells..

    50% from hi

  76. Hi Ohad, Do you have any opinion on AXON licensing agreement with Oxford on their gene therapy program for Parkinsons disease. Thank you Peter

  77. hi Ohad,

    do you see any value in FPRX Five Prime?

    cash level quite good…. big part of market cap


  78. James (GWPH) – Haven’t been following the story closely but looks like a great achievement. Not sure what the broad implications are for other companies as there are different approaches here from a single molecule to extracts.

    Frank (SRPT/ONCE) –
    1 – I don’t think so because we are talking about different programs for different indications and target populations. Programs that require lower doses (e.g local delivery to the eye or intrathecal delivery) are obviously more straightforward in terms of production but I certainly hope the industry will catch up wrt manufacturing enough vectors for systemic administration.
    2 – Having an efficient manufacturing infrastructure is an important factor as manufacturing has become one of the crucial bottlenecks in the industry, it also removes the dependency on external manufacturers. For high quantities they may need to use the baculovirus system which is still less validated. I believe that most advanced companies either have or in the process of setting up production platforms. I think VYGR, QURE, MGTX have put a strong emphasis on setting up their own facilities, some with baculovirus platforms.

    Dave (RGNX) – Very hard to speculate there because value in this case lies in the eye of the beholder. If someone buys them, it won’t be for a specific program but for the capabilities, pipeline, next gen vectors on top of their internal programs. This may also explain what NVS paid as it probably wanted to be the market leader in GTX with two approved products soon.

    Dave (KURA) – Yes I still think valuation is reasonable given the data and market opportunity so I plan on holding.

    andre – Thanks.

    Mike –

    OVID – I am following them waiting for a better entry point. I like their approach which appears to be unique and differentiated vs. other GABA agonists and the rationale for Angelman and FXS sounds good but they are still quite far from clinical PoC so no rush there.
    NERV – This year is going to be an “execution” year, i.e not a lot catalysts, overall looks like they are on track on delivering a lot of data next year across different indications. As you can see I own NERV.

    DAn (GEMP) – Good for them. Placebo effect was huge and data set was small but the signal is definitely there including a reduction in hsCRP. Still heistant to start a position, something doesn’t feel right but perhaps this is just my ESPR bias…

    Les (ESPR/GEMP) – Agree the market ascribes a lot of risk to these programs, rightfully so as the bar for safety is very high.

    XENE – No idea…

    Dave (PIRS) – Agree it’s worth watching, interesting pipeline but still prefer to be on the sidelines until they present data.

    Chris (VBIV) – Sorry cannot comment on them..

    Jaime Allen (XENE) – Hard to guess… Potential buyers will probably want to wait to MAD data and more imaging validation with 1101 by the end of the year anyway imo.

    Steve (NCNA) – Not a big fan of their appraoch, so far data are not overwhelming imo.

    DAn (CANF) – Sorry, not very familiar with the story

    Ruhu – I prefer not to do personal recommendation as each investor has a different profile and it’s very hard to pick specific stocks. I prefer the “portfolio approach”.

    Frank (XENE) – I think it’s positive as it shoes they are able to attract new investors without pressuring stock price (and they clearly need the money).

    Alex –
    TRVN – Haven’t been following them for a while. I remember I though it was interesting at the time but still early.
    FMI – I don’t see a competing bidder emerging but that’s what I thought about DMTX (even though the situation here is different with Roche already a sig stakeholder)…..

    dave (ZSAN) – Sorry, don’t knwo them well.

    DAn (CAPR) – Not following the closely but exosomes are definitely garnering a lot of interest on the private side, still a long way to go….

    Peter (AXON) – Still need to look into that.

    Christian (FPRX) – I still think valuation is too high given the lack of clear route to market for the two leading programs.


  79. Ohad,
    As usual, very informative discussion!
    An enjoyable hot summer beach reading.

    What do you think about FCSC as a hedge of KRYS and ABEO? They had a messy financing, but their cure for REDB seems to work very well.
    Since the administration is local, COL7 antibodies were not developed, so they can apply a second administration in 12/24 months.
    They are preparing a package for BTD/RMAT. Plus they have a full manufacturing facility. With RMAT they can expand the current trail to pivotal and be on the market in 2020.
    If they get RMAT, they will check all boxes for investment – cool technology, efficacy, durability (still need to be confirmed with more pts though), manufacturing facility, very low mcap / negative EV. What could be a pottential trigger for you to invest in this stock, if at all?

  80. Ohad

    Can you speak of SNSS. You originally added it your portfolio almost a year ago and the stock traded almost 200% higher within months only to come back to the level of your purchase. As a holder of APTO which also has a BTK inhibitor, would you prefer to add to your SNSS position or would you consider a position in APTO

  81. Ohad,

    AVEO – I am sure you remember – with several catalysts this year and pretty active insider buying.

    Cash-level rather low but burn not high.

    do you think it is worth re-visiting them?


  82. Hey Ohad,
    As always thanks for your insight and answering my questions. Yes, I have seen many bid funding rounds for exosome companies (diagnosis and therapeutics). I believe CAPR will be the first company to have a ph1, they are supposed to get started on their program H2 18.

    My worst performing stock to date, MBVX, which has been plagued with awful news, shady management, and huge cash flow and liquidity issues signed a deal with Boeringer for $11M upfront for a preclinical anybody program. This is no big deal, except that MBVX had a market cap of $5M, I believe. Stock shot up 250% in premarket. The deal validates their platform. Only 9M shares outstanding. Hopefully liquidity will get better… but they are getting delisted too…and moving to the pink sheets which is a shame, even the good news this morning.
    I am still down big on this investment considering I bought a few years ago at $2.50, before the reverse split. But I managed to add 1800 shares at $0.58 just last Friday – count have timed it better!
    Any opinions on their platform–antibodies that are generated and harvested from patients?

  83. Great timing on your post Christian, huge move in AVEO today. You have a crystal ball? 😊

  84. Christian, may not be too late on a dip tomorrow. On the crystal ball question I guess you can say that Insider Trading is a good crystal ball.

  85. Ohad; here is my list of GT companies:

    1. With manufacturing facility:

    2 With Manufacturing facility in progress – in operation in 2019

    3. No info about (someone can help perhaps)

  86. Hi Ohad,

    Thanks for sharing your great insights and knowledge.

    In the next generation IPF (ideopathic pulmonary fibrosis) drug space, do you think any company (e.g. FGEN, GLPG, PFSCF) has a differentiated product AND an attractive valuation?



  87. Ohad is XENE still value or fairly priced or over priced now at around 23m shares outstanding and 210m market cap? Prior to May shares totaled around 14m then they sold 3.4 atm in the May atm now they do another 3.4m atm equaling, yea, 23m shares give or take.

    Also do you have thoughts on KDMN gvhd and ipf?

    thanks as always

  88. Don, just saw an announcement that XENE has entered into a new agreement with Steiffel for $50M ATM equity offering sales. Where did you get your numbers for ATM offerings in May and July? Also Ohad in his last post on XENE had indicated $450-500M as fair valuation so I guess we have a long way to go 😘.

  89. Hey Ohad
    what are the implications of the PICI and UCSF car-t/crispr engineering discovery for he companies in your portfolio. Seems innovation is happening a such a speed ha entire pipelines may be obsolete before hey even get to ph2 or ph3, and that the drug lifecycle is going to get shorter and shorter…. great for patients, harder for companies…

  90. Hi Ohad,

    You mentioned DNLI was not cheap at current price in the beginning of this year. What’s the reasonable entry point you would consider to get in? Thanks!

  91. Hi Ohad
    I no longer see LPTX listed in the Pontifax portfolio.
    Can you talk about the company ?


  92. Ohad
    we were joking recently about using placebo as an effective drug. Actually some are already working on that idea :)
    “Modulation of anti-tumor immunity by the brain’s reward system”
    Tamar L Ben-Shaanan, at al
    Nature Communications; Volume 9, Article number: 2723 (2018)

    They assign the placebo effect in many studies to the activation of the immune system by stimulating the brain. So they had an elegant experiment – delivered the gene hM3D(Gq) via AAV virus vectors, which trigger intra-cellular cascade that leads to neuronal activation of the reward system. Results – reduction of the tumor size and weight compared to mice injected with not activated AVV virus, i.e viruses without targeted gene encoding.
    Probably no value as a single agent, but it can be used as a an immuno-modulator in any treatment arm to compensate for the placebo effect in the control arm.
    Fun article worth reading, showing some unexpected use of AAV vectors …

  93. Hi Ohad
    Why do you think GNCA having difficulty to find a partner despite the innovative approach?
    Too early ,not enough evidence?


  94. Hey Ohad,
    Exciting news this morning regarding CAPR – they have entered an agreement with the US military to use their exosomes as in the field therapeutic stabilizer to reduce morbidity of soldiers. This, if successful, might open a large market and change the way trauma injuries are treated.

  95. Andre (FCSC) – I think it makes sense as a small highly speculative hedge but the way the stock behaves and the recent tiny fundraising is very disconcerting.

    Dave (SNSS) – Yep, there was a lot of excitement but the recent safety turned everybody sour on the stock. No new data so hard to say

    Christian (AVEO) – Given everything going on in RCC, potential generic competition, short patent life and the lack of clear superiority data I don’t plan on adding.

    DAn (MBVX) – I don’t know if their discovery capabilities are that differentiated from other approaches, antibody discovery has become a commodity now and people are focusing on next gen platforms. Their lead program should generate data this or next year, radio immunotherapy is gaining steam based on ECYT and AAA but whole antibodies may not be the ideal delivery tool.

    andre – Thanks. Eventually every company strives to have its own facility. Important for short term supply but in the long run the industry may be better served with large CMO (like other biologics)

    Anna (FGEN, GLPG, PFSCF) – I really like Autotaxin as a target so I guess I’ll have to go with GLPG’s drug, I also like FGEN’s IPF data and the panc cancer data are also intriguing and provocative. Valuation is a different story…

    don (XENE) – Yes, I still think it’s a good long term buy.

    KDMN – Data are too sparse imo

    DAn – Agree about pace of scientific innovation, may not necessarilly be the case for drug development. I am not familiar with a breakthrough technology that hasn’t undergone a long incubation period, sometimes even a decade long (gene therapy, CARs, siRNA). I hope gene editing will be different but I certainly don’t expect that based on past experience.

    Cloud (DNLI) – Hard to say… What I do know that without clinical poc, the stock
    is not anywhere close to what I consider as an attractive entry point.

    eugene p mcmahon jr (LPTX) – Indeed , I still prefer not to comment as I am not following them.

    andre – Very interesting and provocative, not sure how much of that translates
    to humans but I don’t think anybody will argue against psychological/emotional elements as contributing factors in many diseases.

    Al (MGTA) – Yes they do interest me because they are trying to reinvigorate a field that hasn’t seen a lot of innovation in decades. Not sure they have the clinical data to prove their claims but the direction is cool (SCT is a very powerful, potentially curative therapy).

    BLCM – Still following them, less interested now given all the developments in switches and modulators of CARs.

    Alex (GNCA) – No idea, I thought their platform is really neat.


  96. Any thoughts on AUTL? Looks like an intriguing platform with some unique programs.

  97. Ohad
    PTCT is now GT company with completed pivotal trail in AADC and two other Ph1 trails – in FA and Angelman Syndrome. All that from the proposed acquisition of Agilis. Plus they already have a broad pipeline in CNS (dravet, SMA, Aniridia)

    It look PTCT will fit now well in your GT – CNS focused portfolio.
    Just perfect – one stock checks two boxes. :)
    I didn’t like PTCT because of the questionable DMD drug, but this acquisition looks a game changer for me.

  98. Hi Ohad,

    Thanks for answering my question. I came across 2 companies with pipeline in the crowded ADHD market, namely KemPharm (KMPH) and SUPN. KemPharm is headed by Travis Mickle, Ph.D. who developed Vyvance while working at New River (sold to Shire). Current pipeline priority is KP-415, a prodrug designed to “address unmet needs with currently marketed methylphenidate ADHD treatments, including earlier onset (at 30 minutes), longer duration (>=13 hours) and consistency of the therapeutic effect”, and “the possibility of a lower abuse potential”. Shire has first right of refusal for KP-415 due to possible patent dispute (Vyvance and KP-415 are invented by same person). Insiders own 20% and institutions own ~36%. Recent data readout was positive.

    The other company, SUPN, also has an ADHD drug candidate in its pipeline that might have a >=$1 billion potential. Institutional ownership is >90%, but some insiders are unloading shares. Do you think either company has de-risked and differentiated products in ADHD? How about their current valuations?

    With regard to ECYT, do you think their platform is applicable to other cancer types besides prostate cancer? Why or why not? Many thanks.

  99. Hey Ohad
    is it time to look at TRVN again? market cap $100M / cash on hand I think is $60M.
    Their migraine program passed ph1 and is about to go into ph2. Novel MOA hat seems okay regarding side effects / risks. They also just hired a solid scientist with proven CNS career as CSO.
    Thanks for your opinion?

  100. I was looking at the ADVM corporate presentation which states they have $247M cash as of May 2018 which is sufficient to fund clinical programs into end of 2019. How do you burn that much cash with no active Phase2 or Phase3 programs?
    Also, would appreciate your insight into the PARP space. Appears both CLVS and TSRO are undervalued. Thx.

  101. Hi Ohad,

    I have a question with valuations in biotech. For example, the commercial potential number you calculated here, how did you arrive at that number? Is that an estimate of peak sales? Do you agree with applying a multiple to peak sales to get an estimate as to what a company should be valued at? I have heard 3x peak sales being thrown around as a rough way to arrive at a market cap. for a biotech, but I know each company will have many idiosyncrasies you have to account for. Appreciate any insight. Always learn a lot from you.

  102. Hey Ohad,

    What do you think are the implications /potential of gamma-delta T cells? Another innovation coming to the fore (that ends to be tested). GammaDelta Therapeutics seems to have put together a strong team, and GILD just partnered with Gadeta. The advantaged of gamma-delta T cells (supposedly) is their sensitivity and rapidity of action – they can respond to “stress antigens” and may recognize an array of different diseases or conditions very early on. They may also work off the shelf and not need to be personalized for each patient.

    Takeda is a lead investor in GammaDelta Tx, which raised $100M last year. But they still have a way to go before entering the clinic. GILD enter the field, and I would expect other large companies to do the same.


  103. Regarding my previous post:
    I am an investor in MBIO and I wonder if you have a take about how smaller first-gem CAR T or I/O companies (BLCM, TPIV, Adaptimmune, etc) will be able to compete with GILD and keep up with the pace of innovation without being blocked out.
    Do you think that companies will use the new discoveries for their own research and worry about IP and licensing of the IP at a later stage? It seems that this is the route that AVXS and ABEO chose (they only recently agreed or amended a license with RGNX). ABEO is also using CRISPR technology for one of their early stage programs, and I do not think they have licenses any of the IP, which is still in contention between the Charpentier camp and MIT.

  104. Ohad

    You had added ECYT a couple months ago. With several drugs such as zytiga and xtandi already approved for prostate cancer and a generic zytiga coming to market soon will there be much room for a new treatment if there Phase 111 is successful. With a 300% rise in the stock price this year and a market cap of 1 billion, the valuation appears rich.

    Thanks for all you do Ohad. Your track record speaks for itself.

  105. Ohad thoughts on $mgtx at this level?

    I see they have fast track for xlrp while agtc and nite do not….is their delivery different?

    Plus I think they are the only public Gene bio targeting xerostomia.

    I’m in

    Also fcsc have u looked into them yet?


  106. Hi Ohad
    can you comment on NTEC ?
    Dan mentioned TRVN ,what about AUPH ? I’m thinking to get in..


  107. Ohad, what do you think about the whole sector in the next 1-2 years? What Kind of sentiment do you expect? Many Stocks got Really expensive so maybe Theres a new correction period coming?

  108. Hello Ohad…. You expressed an interest in DENALI THERAPEUTICS this past January. Denalis valuation has significantly declined ..Are you considering adding it to your portfolio???

  109. Ohad I asked u about $mgtx
    Forgot to ask if they are doing anything different/Superior to $agtc ….alot of overlap


  110. Emmanuel (AUTL) – I llke the bispecific approach, which, theoretically may be able to cope with antigen escape (a documented resistance mechaism with CD19 CARs). Data set is still very preliminary.

    andre (PTCT) – Agree PTCT is a different company with a diversified pipeline and in contrast to ataluren, the new programs (SMA, AADC) have encouraging clinical data. I like the Angelman syndrome program, still early and not sure they are using the best capsid though. Definitely worth tracking.

    Anna – Sorry, don’t know KMPH and SUPN well.
    ECYT – At the moment the PSMA program should be viewed as a single asset, but the company clearly has knowledge and capabilities from its small molecule drug conjugates (SMDC) days. This means they could develop small molecules for other targets, but this is relatively tricky. With respect to the PSMA program, the target might be expressed in subsets of other tumor types, see recent report on breast cancer so there may be room for expansion.

    DAn (TRVN) – I think you’re right. The migraine program is interesting indeed, very high risk of course without efficacy or long term safety data. Still need to be careful interpreting potential differentiated profile (seizures) given experience with their selective opioid.

    Manish (ADVM) – That’s a good question, maybe they are just being conservative…
    Regarding PARP companies – The market (BRCA+ tumors and HRD+ ovarian cancer) is simply not big enough to support these valuation. Amazing TSRO is traded at the same levels it did before the P3 data.
    Regarding valuations – I think that a multiple of 5-7 is what we have seen historically for highly innovative programs with good regulatory/patent protection. 3 sounds a little low, might apply to programs that are not competitive enough or have weak IP.

    DAn – Agree with all those potential advantages, still remain to be proven in humans. I would also add enhanced selectivity using a CAR+ endogenous gdTCR. Expansion is a major issue…
    I think it’s gonna be tough to compete in the CAR space without unique technologies, simply too much competition.

    Dave (ECYT) – Agree it isn’t cheap and plenty of risk ahead but clinical data at ASCO were too good to ignore. I think this drug can easily be a $1B franchise.

    Robert goulet (MGTX) – I am following them, I like their broad pipeline and the xerostomia program is very neat in my opinion.
    Yes the vectors they are using for their RPRG program utilizes AAV2 from what I recall, AGTC and NITE use modified/optimized vectors.

    Alex – Sorry, don’t know NTEC well. TRVN might be interesting at these levels, AUPH is a pass for me.

    Foresee – I think we are bound to have a correction (sector specific or broad), hard to predict timing but valuations on average are not sustainable imo, especially te recent pre-clinical IPOs…

    Bouschka (DNLI) – Still too expensive IMO…

    Robert goulet (AGTC/MGTX) – Agree, a lot of overlap. They are using different technologies (vectors, promoter, transgene codon optimization) for the same indications but hard to predict clinical outcome.


  111. Ohad
    do you have an opinion about GBT?
    It looks they have an approvable SCD drug – the recent data from Ph 3a looks good. BLUE has one time GT solution down the road, but it will be more expensive, compared to GBT drug, which is oral ones per day,
    Is the market is big enough for two companies?

  112. Hi Ohad,

    Have you done research into Aileron (ALRN) and their Stapled Peptide Tech?
    They have multiple readouts before the year end for ALRN-6924 in PTCL and AML.
    Has been crushed lately and thinking of taking a position as it’s near cash value now.


  113. Thanks, Ohad
    Yes, it seems that there are risks for TRVN250–hey are trying to position the drug for acute migraine–thus restricting the market and making the risk/reward propositions for patients more interesting. However, this will clearly reduce addressable market size. There is also a risk of execution, given their are preparing to launch their pain drug, and as an investor in SGYP I have seen how damaging the going alone strategy can be to share values. SGYP has not recovered and have struggled to get growth–but they are competing against a AGN.

    On the positive, TRVN has been managed to unlock value by signing some licensing deals (for the pain drug) in asian markets. Hopefully they can do the same for EU and other parts of the world, and mitigate liquidity issues and keep their cash burn under control.

    I just started a position yesterday at $1.43.

    What is your take on PFE CC with respect to their interest in Gene Therapy acquisitions or partnerships. They hinted that at the right valuation they are interested. ADVM and AGTC seem the best value for money right now. Would you agree? Only concern with DVM is that they keep changing CEO- and one has to wonder why.

  114. Ohad

    As Dan has mentioned, Pfizer’s C.E.O. stated they may be looking for smaller deals in the gene therapy space. Earlier this year you were underwhelmed with Sparks hemophilia A drug data, but had stated the stock had hung in well due to other programs in their pipeline. Can you talk about the program your most excited about and are you considering adding to your position in ONCE on this 20% correction over the last month

  115. AZEDRA has just been approved by FDA and ph3 PSMA-targeted SPECT Imaging Agent will be presented this q.
    Ohad, do have an opinion regarding Progenics (PGNX) ?

  116. Ohad
    SGMO will report Ph 1/2 data for MPSII on Sep 5. Oral presentation.
    “…ZFN-mediated in vivo human genome editing”
    RGNX is still enrolling for their Ph 1/2 MPSII trail:
    NAV AAV9, encoding I2S. 1.3 and 6.5×10^10 GC/g brain mass

    Two different approaches, hopefully both work against this devastating disease.
    What is your prediction about both companies odds to succeed?.

  117. andre (GBT/BLUE) – Don’t know the SCD space well but I am pretty sure it is big and diverse enough for the two approaches, not to mention the fact that we still haven’t seen “landslide” efficacy from BLUE.

    John (ALRN) – This is one of my biggest disappointments as their preclinical data and capabilities looked really good and it seemed that they have cracked the challenge of peptides against intracellular targets. Clinical data are underwhelming imo, P53 continues to be unbeatable especially in solid tumors.

    DAn – I don’t know what Pfizer’s appetite is for ophthalmic programs. From what I know they aren’t active in that space so I don’t see them buying AGTC. ADVM has other programs so hard to say.

    Dave (ONCE) – Actually there are indications the HemA program is back on track based on comments from management but need to see data, probably at ASH. I prefer to wait and see how the LUXTURNA launch goes.

    Rüdi (PGNX) – Not very familiar with this program but targeted radiotherapy is definitely starting to pick up.

    andre (SGMO/RGNX) – I put my money on RGNX, not a big believer of zinc fingers and canonical AAV expression is much more clinically validated. As you say, hope at least one of these approaches works…


  118. Hello Ohad,

    $RUBY and $ERYP have similar technologies concerning red cell therapeutics.

    But they have very different valuations. Can you take a look?


  119. Zyme

    Ohad, do you plan to increase your Position After the recent sell off? Maybe market punishes Zyme too due to the Clinical Hold for Mersana. How do you see zw25 in the competitive her2 – market? Is there a real Chance ? Zw49 will be interesting to See but the market seems to be careful about her2 adcs.

    EV about 250m still looks like a Nice RR

  120. Ohad I was wondering whether there are any news for KURA?

    thanks for your good work


  121. Hi Ohad, All,

    GEMP tanked heavily today on a FDA hold. Would appreciate your thoughts on possibilities for redemption. Thanks.

  122. Ohad
    ONCE, KURA, BOLD quite negative market reaction. What is your take on that?
    BOLD delayed the Pompe program but it is preclinical. Is it a serious issue to worry about?
    KURA starting registration trail by the end of the year. Is an earlier start expexted?
    ONCE is having problems with 2e12 and need steroids but BMRN doesn’t with 20x that level. Capcid issue?

  123. Hi Ohad,
    Amicus Therapeutics (FOLD) is going to acquire one or more gene therapy programs by the end of this year. I think, one of the programs should be in Pompe disease. Is it on your watch list?

  124. Ohad
    SRPT just acquired 3 CNS programs, incl one in Pompe.
    Altogether they now have 11 GT programs – by far the most diverst GT portfolio.

    Alex, 4 companies have Pompe programs, all in pre-clinic:
    ONCE, BOLD, AVRO and, as of today, SRPT
    I guess, if FOLD wants to buy such program, they might be able to afford only BOLD. The others are too expensive

  125. Toby (RUBY/ERYP) – Agree, valuation gap is very interesting. Don’t know the companies well but it looks like ERYP’s focus is on oncology (asparginase) whereas RUBY focuses more on ERT opportunities (PKU, homocystinuria, hyperoxaluria). Technologies should also be different to some extent and very importantly, RUBY is a US-based company backed by Flagship.

    Swoboo (ZYME) – I don’t plan on adding but definitely keeping my position. Still think they have efficacy signals in breast and gastric cancers, not as potent as Daiichi’s ‘8201 but safety looks very good and it can be combined with other treatments. I wouldn’t write off Zw49 yet, from what I recall the payload is an auristatin derivative (like SGEN) so different class than what MRSN has.

    don (XENE) – No, I didn’t.

    Xavi (OVID) – Still haven’t taken a closer look but agree it looks mixed at best.

    Karlo – I am actually working on one right now, it’s been hectic with the new fund so didn’t have a lot of time for public stocks…

    paul (ONCE) – Yep, reaction is justified in my opinion although the immunogenicity issues may be resolved, burden of proof of on ONCE. They still see good expression wit relatively low doses so they could make a comebac eventually.

    Scott (AFMD/PIRS) – Both have low valuations, esp AFMD and both focus on bispecifics. I prefer PIRS although they don’t provide a lot of info on their targets, not a great believer in AFMD’s CD16 approach.

    Christian (KURA) – From what I knoe they are enrolling patients in their pivotal trial H&N study at a reasonable rate, next data expected at ESMO.

    Les (GEMP) – I don’t know, never liked that stock….

    Andre (ONCE/KURA/BOLD) – Reaction in ONCE is justified in my opinion given their 2B+ market cap, BMRN used prophylactic steroids in all their patients so it’s hard to compare but agree it’s an issue ONCE need to resolve.
    not overly concerned with BOLD and KURA sound overall on track (data in Oct at ESMO).

    alex (FOLD) – Not following them closely.

    andre (SRPT) – Well done, great BD work. Agree it’s becoming a diversified GTx powerhouse.


  126. Morning,

    I think the time is now to get back in Aduro $ADRO with the upcoming release of STING data. EV of only $125M with $300M cash in the bank plus lots of milestones coming there way if the data hits from Novartis.

  127. Ohad
    FCSC: I was reading the transcript of the concall today. You were right – the recent financing is very concerning- warrants etc. However there were some interesting bits of info:
    – they started Ph2 and already enrolled 4 pts. Goal is 6-8 pts,
    – expected enrollment completion Q3, data in early 2019
    – it looks they already applied for BTD and RMAT
    – if they get RMAT (looks quite plausible, I believe) they will expand the trail to pivotal with potential approval in 2020.
    They have cash until Q4 2019, enough to complete the pivotal trail and announce the data.

    Today I bought some shares, mainly as a hedge for ABEO and KRYS
    I do expect that you are buying something this weekend with the FMI cash, so if it is FCSC I am well positioned :).
    If not – I still feel comfortable to hold the stock for 2 years at the current almost zero EV

  128. Hey Ohad,

    Any opinions on AVRO and FIXX? AVRO $1B market cap. 4 GTx programs (3 of which preclinical) – while SRPT just gained 3 extra GTx programs through a $30M equity investment (not sure what the other terms were / undisclosed).

  129. Hello Ohad,
    Are you aware of a private biotech Bexion Pharmaceuticals – that has been in the news recently?
    They are only now planning for a phase II trial (and other phase I), but seem to be onto something, esp in glioblastoma multiforme.

  130. Hi Ohad,

    It would seem Amgen’s announcement today to reduce Repatha’s list price could weaken ESPR’s BA story. What are your thoughts? Also, are you concerned with the slight delay in the release of study 2?


    P.S. Thanks for the blog, very transparent and informative.

  131. Ohad…… I was going back to review your comments on SNSS, when I came across your favorable response on Aug. 30, 2017 on gene therapy co. MeiraGTx ! They are not in your Portfolio……Is the valuation too high or are you considering adding them ?

  132. of course like your web site however you have to take a look at the spelling on several of your
    posts. Several of them are rife with spelling issues and
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