Endocyte – And now for something completely different

Last week’s approval of Alnylam’s (ALNY) Onpattro, the first FDA-approved siRNA drug, serves as a reminder for the bumpy road new technologies go through on their way to the market. From an investor perspective, siRNA has gone in and out of fashion over the years with dramatic shifts in market sentiment. It started with unrealistically high expectations, deteriorated to deep pessimism due to clinical setbacks, followed by gradual sentiment improvement in recent years (with some hiccups along the way).

This pattern is typical for many fields in biotech (recent examples are gene therapy, immuno-oncology, genomics), which sometimes took decades to realize their potential. The good news is that once a depressed field “rises from the ashes” it is usually for a good reason, i.e. it is backed by real progress. This appears to be the case in targeted radiotherapy (TRT), a neglected field until recently that may become the next big thing in oncology.

Targeted radiotherapy’s checkered past…  

In contrast to siRNA, targeted radiotherapy (TRT) has never been very popular with investors. It had a brief wave of activity in the early 2000’s, culminating in the approval of Bexxar and Zevalin in lymphoma. Despite good clinical efficacy, the two agents (both targeting CD20) were commercial failures because they couldn’t compete with Rituxan-based regimens that were more straightforward to use. TRT agents come with a host of logistic issues: They have a short shelf-life, require special shipping and handling, necessitate special training and carry radiation exposure risks. It isn’t surprising physicians preferred the simpler alternative…

More importantly, antibody-based TRT (also called radio-immunoconjugates) like Bexxar and Zevalin have a long circulation time in the body, leading to significant bone-marrow toxicity as well as damage to highly perfused organs (liver, lungs). This profile may be sufficient for efficacy in lymphomas (cancer of the bone marrow) but not in solid tumors where higher exposure is required.

…but recent data point to a revival

Data from three different TRT programs are behind resurgence in investor interest: Bayer’s Xofigo for prostate cancer with bone mets, Novartis’ (NVS) Lutathera for neuroendocrine tumors (NET) and Endocyte’s (ECYT) Lu-PSMA-617 for prostate cancer.

A key feature of all three is the use of small targeting moieties (In Xofigo the radioisotope is also the targeting moiety), which leads to a short exposure and quick clearance via the kidneys. This exposure profile enables the administration of higher radiation doses, leading to better tumor accumulation with limited toxicity (kidneys are relatively radio-resistant and can be further protected pharmacologically).

First demonstration of efficacy was with Bayer’s Xofigo, approved for prostate cancer based on a modest survival benefit. Xofigo does not have a targeting moiety and it accumulates in bones based on a structural similarity of Radium-223 to calcium. In 2014, Bayer bought Algeta, Xofigo’s original developer, for $2.9B. Xofigo is considered a disappointment with $400M in annual sales (partly attributed to its narrow label) but it still serves as a proof of concept for a radiopharmaceutical. It also clinically validates alpha emitters as a therapeutic class.

The next validation came from Novartis’  Lutathera(via the $3.9B acquisition of Advanced Accelerator Applications), approved for NET. Lutathera is comprised of a peptide targeting somatostatin receptors linked to Lutetium-177. In a P3 study vs. an active control, Lutathera led to an impressive PFS benefit (HR = 0.21) and a strong OS trend.

Lutathera P3

Source: Strosberg J. N Engl J Med. 2017 Jan 12;376(2):125-135.

It is still early to assess Lutathera’s commercial performance (approved by the FDA in Jan 2018) but launch trajectory looks good with sales of $24M in Q2/2018.

Lutathera

Endocyte – Transformational deal, strong P2 data

Endocyte is a newcomer to the TRT field following the in-licensing of Lu-PSMA-617 from ABX. This small transaction transformed Endocyte (and its market cap), which now has the most prominent TRT program in development. Lu-PSMA-617 consists of a small molecule targeting PSMA linked to Lutetium-177. The company recently started P3 based on strong P2 data that were published earlier this year. Lu-PSMA-617 led to a PSA response in ~60% of patients, and more importantly generated an objective response in 82% in 17 response-evaluable patients with soft tissue lesions.

ECYT - PSA50

These results compare favorably to other approved agents and may under-represent Lu-PSMA-617’s effect as the ongoing P3 is evaluating a longer treatment regimen. Importantly, the drug was active in patients who failed Zytiga or Xtandi, the leading prostate cancer drugs and the effect was consistent irrespective of prior treatments. Lu-PSMA-617 is being evaluated as monoterapy but it can potentially be combined with other agents in the future given the different MOA and relatively mild safety profile.

Significant commercial opportunity

There are four prostate cancer drugs on the market that can be used to gage Lu-PSMA-617’s commercial opportunity: Zytiga, Xtandi, Xofigo, and Jevtana. Their respective commercial performance varies widely, as Zytiga and Xtandi generate $3.5B and $2.5B, respectively, whereas Jevtana and Xofigo are niche products with ~$400M in global annual sales. Lu-PSMA-617 should be somewhere in the middle as it appears more efficacious and better tolerated than Xofigo/Jevtana. Despite its potential broad applicability (85% of prostate cancer patients should be treatment-eligible based on PSMA expression), logistics issues may prevent it from becoming a multi-billion franchise like Zytiga and Xtandi, but peak sales of ~$1.5B appear achievable.

Endocyte just strated a P3 study which will take 12-18 months to readout (interim analysis, depending on regulatory feedback expected this year regarding approvable endpoints). The only important near-term catalyst could be data from an investigator sponsored study comparing Lu-PSMA-617 to Jevtana that started in January.

Despite the lack of catalysts and potential for negative ones (technical , safety issues), Endocyte may become an attractive acquisition target given the strong efficacy, favorable safety profile, novel MOA in a highly competitive and lucrative market (Zytiga will become generic soon). Many companies are not (yet?) interested in radiopharmaceuticals but an obvious acquirer is J&J given on their franchise in prostate cancer and involvement in another TRT company (Fusion Pharmaceuticals).

Portfolio updates

I am selling Foundation Medicine (FMI) at a 510% profit following acquisition by Roche, announced in June.

biotech portfolio - 13-8-2018 after changes biotech etfs - 13-8-2018

195 thoughts on “Endocyte – And now for something completely different

  1. Have you ever looked at ATNM? Also using radiatherapy… corporate history does not bode much confidence, but I remember seeing that their safety profile is very good compared to the SGEN program that was terminated due to toxicities.

  2. MBIO just bought a GTx program form St Jude’s hospital. It is already in ph1. Wonder if you have any opinions about it? MBIO has low valuation. I suppose they’re diversifying their pipeline because of how competitive the CAR-T is becoming.

  3. Dan (ATNM) – Thanks. I don’t think whole IgG is the way forward with targeted radiotherapy. From what I recall, their AML data was somewhatnoisy and hard to interpret.

    MBIO – Not familiar with the program, need to understand the differentiation from other SCID programs.

    Ohad

  4. Ohad
    Thanks for the interesting write up on TRT. I remember 4-5 years ago it was considered a loosing concept – logistics, special treatment centers, and such… Nice to see a revival of this fairly straightforward ADC type of concept.

    Any opinion on CKPT – they have a late breaker oral presentation on WCLC, Sep 24 – targeted therapy for NSCLC with EGFR mutation
    They claim 3-d generation EGFR TKI, activity against T790M with no activity against wild (normal) EGFR.
    Late breaking oral could mean that they have some positive data for efficacy and safety form their Ph1/2 trail.

  5. Hello Ohad,
    Thank you for this forum- it has really been helpful in more ways than financial gain.
    I had posted a question at the end of the previous segment- if you are aware of the work being done by private biotech company Bexion? (The reason that I ask is that they do allow placement of private funds, albeit at higher levels)
    Their “star” patient with glioblastoma m seems to be approaching the 5 year mark (although only the most recent 20 months seems to be with their drug). And now John McCain also seems to be under treatment. Hmmm,
    Lawrence

  6. Hey Ohad,
    have you had a chance to look at RLMD – they are running a phase 2 study in MDD. The PI is Maurizio Fava, the inventor of the sequential parallel comparison design. Study is recruiting only 60 patients so could read out quickly.
    Dan

  7. sector sentiment

    Are you Holding the companies in your Portfolio During the Next quarters? Do you Plan to increase your BIS Position?

  8. Hey Ohad,
    CGEN is about to initiate two ph1 programs (one partnered with BAY). Some people have lofty expectation for their lead program, or hopes it may be as effective as checkpoint inhibitors. Any views? I started a position yesterday.
    Thanks,
    Dan

  9. Ohad

    XENE is expecting to present data from its XEN1101 Phase 1b TMS pharmacodynamic study at the end of the month. Is this a final readout from there interim results they announced in May and is there anything you will be most focused on with the upcoming data. Also does the XEN1101 or XENE901 program have greater value enhancing possibilities for the company.

  10. Hi Ohad,

    My question was posted on your last article, but was wondering if you have any opinion on Adruo $ADRO STING upcoming data? Pre-clinical looks like they are on to something big. Large milestone payments upcoming with Novartis and EV of only $155M as of now with $300M cash.

  11. Hello Ohad,

    do you know Arix Bioscience plc (LSE:ARIX) ? They do similar things like Pontifax Ltd :-) For example they have a big stake in $AUTL. Actual the share price is very low. Do you have an opinion?

    Today Ladenburg gave $ACHV a PT of $12. Actual the pps is only around $3. Laden lead the last offering, the price was $4 in May. They are developing a drug for smoking cessation. The potential looks enormous. They use Cytisine for the drug, this is a plant-based alkaloid. The company is off the radar. Do you think this a good gamble?

    Thanks Toby

  12. …$ACHV
    There already exists drugs with Cytisine especially from Bulgaria. The question is will Achieve Life Sciences be able to protect their new drug with a patent? It’s a natural substance. I couldn’t find a statement on their website.

    It’s a very little company. If you have no time or interest I can accept and understand!

    But I think ARIX.L is interesting for you.

  13. Hi Ohad
    I recall you invested in EXEL privately ,still holding? What is the reason for the weakness in the share?
    Do you think now its a good price to enter?
    Thanks

  14. Hi Ohad!,

    what are your thought about the future catalyst that will move the needle in SNSS?. Do you expect them before the next CC.?

    Are you invested in SNSS because the valuation gap with ARQL or because you think is better science?

    Thank you!

  15. Ohad
    Do you follow ATRA? They expect approval next year and to be on the market in 2020. Nice pipeline but not a single partnership?!
    Is it a red flag or they just don’t need that. Cash is ~450M – enough until approval

  16. Nice development at BOLD – RMAT granted for XLMTM. They might expand the current P1/2 into pivotal and shorten the path to market by 1 year (from 2021 to 2020).
    By that they are “promoted” my 2020-graduation-club (ABEO, BLUE, NITE, VYGR, QURE, ATRA, ECYT ONCE ALNY)

  17. Ohad–Thanks again for an insightful report. Lutathera may overestimate physician adoption of PSMA-617 since there are so few systemic options in carcinoid tumor, unlike prostate cancer. As you correctly state, the logistics also include oncologists “referring away” to hospital-based nuclear medicine or whatever mechanism has been set up to deliver the radioisotope. There always seem to be some resistance there as well. That being said, I agree with you that the data from Lancet Oncology are promising and the drug will likely get approved barring an unforeseen safety issue. Hopefully, drugs like Lutathera will help improve treatment pathways for oncology/nuclear medicine interaction.

  18. Hi Ohad,
    1. Endocyte paid $12 million plus some stock to acquire PSMA-617, while Bayer bought Algeta, Xofigo’s original developer, for $2.9B and Novartis for $3.9B. I am wondering why would ECYT get PSMA (potential cancer blockbuster) so cheap?

    2. Do you think PSMA be way more expensive than Xofigo due to the need to pre-screen with dual PETs? where do you think it cost compare to Xofigo.

    Thanks

  19. News yesterday out of U of Penn regarding GTx for retinitis pigmentosa.
    I think U of Penn is licensing the GTx from OPTH.
    OPTH collapsed tears ago after it’s failed drug to compete with Eylea (REGN).
    Do you see any potential for OPTH given its current low valuation and this news from UPenn in R.P.?

  20. Hey Ohad,

    What do you think of CFRX and the release just out now indicating their drug drug can resensitize bugs (such as Staph Aureus) to penicillin and other antibiotics. This may make their drug a combo therapy used with any antibiotic course? If this is the case this could be huge.
    Dan

  21. Hi Ohad, Epizyme (epzn) showed some weakness in recent months due to the partial clinical hold. Do you think it’s a good time to get in right now? Thanks!

    Jinyu

  22. Hello Ohad ….. Would you please comment on the late breaking oral presentation by ESPR at the European Society of Cardiology Congress that is in the news today.Thanks in advance!

  23. andre – Yes, I don’t know what is more mind boggling: the amount of time much time it takes some technologies to mature or the fact they eventually do.
    CKPT – Don’t know their EGFR program well but it is going ot be an uphill battle vs. Tagrisso unless they have a clear differentiation, which will be hard to demonstrate in P1 imo. They could eventually take market share as Tagrisso is the only approved 3rd gen EGFR inhibitor but I prefer to wait for the data.

    lawrence sheff (Bexion)- Thanks. Not familiar wit the company but after a quick look at their corporate deck I feel data are quite limited and the story is not robust enough imo (mechanism/exposure in humans/ efficacy). There have been a lot of programs with such index patients, especially in GBM and unfortunately usually they don’t pan out.

    Dan (RLMD) – Wasn’t aware of them, looks like they have an oral NMDA antagonist, an interesting proposition, IP is probably weak (methadone derivative), not sure how strong their biology is. In these type of projects I prefer to wait for the data.

    Anger (BIS) – It’s definitely something I am considering as we are in one of the longest bull run in history in general and in biotech as well. I do intend to keep the stocks I own long term because it’s impossible to predict near term stock movements but overall I still think correction is due and valuations are fairly high.

    Dan (CGEN) – I prefer not to discuss Israeli companies.

    Dave (XENE) – Beyond the TMS signal, the most important readout is the safety profile in te MAD portion. Even a rare safety event could kill these programs.

    John (ADRO) – Agree preclinical data for STING agonists (as well as similar targets like RIG1) is very inteersting, the problem is that so far the translatability to humans with IO agents has been very weak. Prefer to wait for the data, which will probably be inconclusive to some extent given the trial design.

    Toby (ARIX) – Prefer not to comment on the stock as we are collaborating with them, good guys. I do like AUTL, though. Early data but rationale is very strong imo.
    Don’t know ACHV, sorry.

    Alex (EXEL) – Yes, still holding a small portion. Not sure what is the cause of te current weakness, but this isn’t unusual for companies 2-3 years post launch when the dream factor is gone and there are hard numbers. Their current run rate is ~$600M so if it continues to drop could be an interesting opportunity.

    James (SNSS) – Prefer not to comment. Pontifax is an investor in ArQule.

    andre (ATRA) – Sorry, don’t have a concrete opinion there.

    andre (BOLD) – Yes but not overly surprising given te indication and data. Perhaps not a home run like the initial AVXS but definitely a signal.

    Gary (ECYT) – ECYT is targeting last line patients without a lot of treatment options so if they generate good P3 data I think ‘617 will be well received.

    AJ (ECYT) – That’s a very good question, one of the best BD deals ever in biotech, no doubt. I think the NVS/AAA deal contributed a lot to 617’s visibility. At the moment I am not concerned about costs, pricing will be driven by clinical benefit at the end of the day imo.

    Frank (OPTH) – Didn’t think it was related as they were using gene editing.

    Dan (CFRX) – Sorry, don’t know the story well.

    Jinyu (EPZM) – Stock is still at 800M so not that cheap imo given the recent safety overhang.

    bouschka (ESPR) – Not a lot of new information, next P3 readout will be much more important.

    Surab (ESPR) – Hard to speculate but given the 1-2B sales potential I think a 4B
    buyout is realistic.

    Ohad

  24. Ohad, you mentioned that biosimilars will have a significant market Share in the (Near) Future but you dont hold any stocks.

    Whats the reason for this ? Too expensive? Do you like Momenta i.e.?
    Thanks!

  25. Ohad

    Regarding ESPR data readout. In reviewing there data just released it appears that BA + Zetia combination resulted in 3x the rate of developing a urinary tract infection than either BA or Zetia alone in a 12 week study. Is that a concern?

    Regarding AUTL doesn’t the valuation appear rich at 1b?Would you wait for the price to come in before starting a position

  26. ESPR

    Are you more Optimistic about BA Approval After the recent Data release?

    What do you think about the Cvot requirement?

    Btw uric acid level was Noted before. Not a big Issue imo.

  27. Hey Ohad,
    Would love to hear your view on ESPR and XENE results.
    For XENE seems like they will be able to enroll a ph2 and generate results rather quickly.
    Also, what do you make of the AFMD deal and NK / cell therapy cos. How do you rate FATE, especially since you say you like AUTL.
    Thanks
    Dan

  28. Karlos (ESPR) – Not very concerned there, key safety finding will be Study 2 next month. Efficacy on top of Zetia was somewhat disappointing.

    Carlos – I focus on innovative products and not very familiar with the biosimilar field. Nevertheless, most biosimilars are being developed by large biopharmas (Amggen, PFE, BI, Biogen) so not a lot of pure plays.

    Dave (ESPR) – Not overly concerned.

    AUTL – Ideally yes but I don’t expect price to come down significantly unless a major market correction occurs (or negative data, of course).

    Labut (ESPR) – I am slightly more optimistic on the safety front but the Zetia combo data was a little disappointing. I still think there are enoughpatients who could benefit this drug (interesting subset analysis in statin resistant pts that needs to be corroborated prospectively).
    I think it will get approved without CVOT, but they will have to show some benefit in order to become a dominant product.

    Habulm (XENE) – Data are positive, largely expected, always nice to see a relatively clean safety profile and TMS signal looks good.

    Dan – Re ESPR and XENE , see above. I would characterize both is positive but nothing overwhelming.

    AFMD – Good for them! I was never a big believer in their approach but apparently Roche are.
    FATE and AUTL are very different IMO, prefer AUTL even with the valuation gap.

    Ohad

  29. ADVM: what is your take on the long-term NHP efficacy data? It shows prevention of Grade IV CNV in the animal model and exhibits 3 ug/mL of aflibercept (not sure the level in vitreal and retina). Is anti-VEGF activity Cmax driven or steady state driven? Is 3 ug/mL clinical meaningful? In the aflibercept trial, the vitreal Cmax is 900 ug/mL.

    For the A1AT program, AGTC tried and failed with a different vector and route of administration. Does ADVM have a shot with AAVrh10 and IV/IP administration?

    How does the HAE program look like?

  30. Ohad

    for KURA, J&J recently gave up on the right to be first to (re)negtiate for an exclusive license for tipi. do you read anything into it?

    the drug is rather old, so patent life is short… is that considered in your calculation?

    thanks!
    Christian

  31. ONCE,ABEO,RGNX

    Are you still positive at current valuations?r/r? What key catalysts are you waitiing for in 2018?

    Thanks to you Ohad, very nice work!!

  32. Hey Ohad,

    What’s your take on the Stanford study on Ketamine and use of opioid receptor blocker? They are suggesting Ketamine works in different phases – first activating the opioid receptor, then the glutamate. Although researchers say Ketamine does not have high affinity to opioid receptor, this study raises questions about addiction, etc.

    What do you think are the implications for the 5-6 companies involved in the field?
    AGN
    SAGE
    JnJ
    VTGN
    APTX
    RLMD

    Thanks

  33. Ohad
    What do you think about AXON Parkinson Lentiviral vector program.
    The capsid contains three genes required for dopamine synthesis ?!?
    The primate data look really solid – dopamine level and symptoms improvement – both stat significant..
    They had a checkered history, failed in the 2 x past badly.
    But it looks they refocused into gene therapy, got some good new hires – CTO from ONCE, VP R&D from AGN, VP clinical dev from PFE

    Their story starts to look like ECYT – a lot of failures, until they licenced something valuable, less than a year ago. They were trading 1.40, today 19.70.
    And the stock price of AXON looks similar to the onset of ECYT after Oct 2, 2017 ECYT – up from 1.40 to 6.50 on the news, retreat to 3, and from 3 to 20 in a remarkably steady increase
    AXON – up from 1.50 to 6.60 on the news, retreat to 2.10, today at 2.50, I guess on the way to 20 in 1-2 year :):)

    What about adding them to the GT basket – strong science (from Oxford Bio) strong team, 100M cash, low valuation (300M), non-human primate proof of concept, no induced dyskinesia compared to levodopa…..
    Plus a second program in Oculopharyngeal Muscular Dystrophy, Ph 1 to start early 2019. And pre-clinical programs in ALS and FTemp Dementia.
    Looks a perfect fit to your GT-CNS basket

  34. Ohad,
    Last May, Sesen bio. (formerly Eleven biotherapeutics) published 3 month data from their ongoing Ph III Vista trial. The are using a next-generation ADC. 13-F filings for the second Q were impressive. Would you look at the science please and let me know if there are any obvious red flags ?

    Thanks, cb

  35. Liang (ADVM) – From what I understand you need long term expression, once you saturate the target (VEGF), more protein likely won’t change anything. Not sure how much expression is optimal, 3 ug/ml sounds meaningful as VEGF levels are typically in the ng/ml range and in some cases hundreds of pg/ml (but VEGF is a smaller protein so you need 4x more Eylea to reach the same molar level). Be that as it may, expression levels cannot be extrapolated directly from animals to humans with AAVs.
    The A1AT program is indeed a long shot but I like it because it’s unique.
    HAE program is less interesting IMO, there are good alternatives and delivery/exposure requirement are unclear to me.

    Christian (KURA) – Hard to say, definitely not a positive but we’ll see updated data soon. Agree about IP, it will be protected only by 7-10 years of market exclusivity which puts a cap on upside.

    Sppi (ONCE,ABEO, RGNX) – Yes I am still positive on all three as all will have clinical readouts in the coming 12 months. For ONCE, it’s HemA, of course and people are starting to look at Pompe. For ABEO, focus is on San Filippo programs and for RGNX it will be on AMD and MPS1/2.

    Dan – Honestly don’t know how to factor that in, very hard to translate scientific data for CNS indications, clinical data trumps everything and very unpredictable in depression.

    andre (AXON) – Ilike their new direction, not familiar with the PD program. The main difference from ECYT is that ECYT knew the drug works in humans. Agree they fit into the GTx basket, need to learn more about their programs.

    conrad barker (Sesen) – From what I see they are doing immunotoxins, hard to give them systemically to get efficacy in solid tumors due to toxicity and immunogenicity. This is why their lead program is for topical bladder cancer

    Ohad

  36. Hi Ohad, would like to know your thoughts on SYBX (especially in light of the recent positive ph1/2a data) and ALRN (given the increased scientific recognition of ALRN-6924 and stapled peptides). Thanks as always.

  37. Ohad –

    What did you think of the SGMO data? It’s exciting we are at this stage of gene editing, but investors seem to have doubts that the approach is working due to lack of IDS enzyme in blood. However, how can you see a decrease in GAGs, dermaten sulfate, heparan sulfate without some therapeutic benefit ascribed to gene editing? Those numbers won’t drop by chance.. Seems like a good buying opportunity to me, but curious to get your thoughts.

    Thanks,
    Nick

  38. Voyager (VYGR) and Uniqure (QURE) both have a gene therapy program AAV-miHTT, but with different AAV type and different design of vector. Based on the pre-clinical data, is there differentiation between them?
    For CNS indications, Voyager licensed a new vector from CalTech. With this new type of vector, what is the likelyhood of success to target CNS with IV administration?

  39. MEIP received FDA’s feedback on their PI3K-delta inhibitor for follicular lymphoma. In the feedback, FDA requested a randomized phase 2 trial to compare the compound with the standard of care for R/R FL. Both daily and intermittent dose regimens will be included. Apparently, MEIP can use a single-arm study. What is your take on this feedback on the registrational trial design? Do you think if their PI3K-delta inhibitor could be a best-in-class molecule as some of the analysts claim, in term of its efficacy and tolerability? The response rate in the phase 1 study of CLL/SLL and FL seem to be high.

    Any other merits in MEIP’s other pipeline programs (HDAC for AML and MCL inhibitor for AML)?

  40. MEIP received FDA’s feedback on their PI3K-delta inhibitor for follicular lymphoma. In the feedback, FDA requested a randomized phase 2 trial to compare the compound with the standard of care for R/R FL. Both daily and intermittent dose regimens will be included. Apparently, MEIP will not be able to use a single-arm study and most likely cannot use ORR as the primary endpoint. What is your take on this feedback on the registrational trial design? Do you think if their PI3K-delta inhibitor could be a best-in-class molecule as some of the analysts claim, in term of its efficacy and tolerability? The response rate in the phase 1 study of CLL/SLL and FL seem to be high.

    Any merits in MEIP’s other pipeline programs (HDAC for AML and MCL inhibitor for AML)?

  41. Richard Baker (ALRN) – Their platform looked really promising initially but it doesn’t look like they have good translation in humans.

    MGTA – I like the approach but clinical data are too sparse IMO. Prefer to wait on the sidelines for now.

    Xavi –
    SYBX – I really like the approach, perfect sense for some metabolic disease like PKU. Not sure what they have qualifies as clinical poc but moving in the right direction.
    ALRN – See above, so far data are weak imo.

    Nick (SGMO) – I think data are inconclusive and I am still skeptical about ZFN as a tool for gene editing. Agree the GAG drop in the higher dose cohort is inthe right direction but patients were getting ERT which probably had a confounding effect. Hope they see IDS in the next cohort….

    Liang (VYGR/QURE) – Too early to tell but Huntington is definitel a promising indication following Roche/IONS data.

    Liang (MEIP) – I don’t have high hopes for this class in general, crowded market. Same applies to their HDAC program.

    Ohad

  42. Hi Ohad,

    Thanks for all the great informative that you share.

    Does the recent announcement by XENE Change your valuation? “Xenon Expands Ion Channel Neurology Pipeline with Addition of XEN496, a “Phase 3 Ready” Potassium Channel Modulator for the Treatment of Epilepsy”

    Not sure what the market is for the drug considering it was pulled previously but GSK is allowing the FDA to leverage their filings to support XENE.

    Any input would be much appreciated!

  43. Hi Ohad,

    How do you see ARWR’s ARO-HBV data? Some say they might be the next GILD. 1.7B cap already, is it too expensive to get in? Thanks a lot!

    Jinyu

  44. Hello Ohad. Very much intrigued with FIXX and their Gene therapy/editing approach. Stem cell derived AAV and homologous recombination. No cutting of the genome that remains a concern with crispr and potential off target effects. HR is the body’s own mechanism of repairing faulty code. Partnership with Novartis. Preclinically they are seeing excellent precise gene sequencing minimizing side effects. Still early but could be a game changer

  45. What upside do you expect for $nite? For a p1/2 Company the stock is quite expensive (700 mil MC). You claimed before that you dont add such stocks to your basket so why is nite an exception? Thank you!

  46. What is your take on ARWR new HBV data? Is HBsAg reduction an acceptable clinical endpoint?

    How do you like their targeted RNAi technology?

  47. Hi Ohad do you Plan to expandiert your GT basket? If yes do you like These companies: VYGR / MGTX? What about their Programs and Price?

  48. Ohad
    You probably missed the last posts from the previous article. Here is part of it:

    FCSC: I was reading the transcript of the concall. You were right – the recent financing is concerning- warrants, etc. However there were some interesting info in it:
    – 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 RMA, at least did not deny it
    – if they get RMAT, they will expand the trail to pivotal, potential approval 2020.
    Cash until Q4 2019, enough to complete the pivotal trail and announce the data.
    How about FCSC as a hedge to ABEO and KRYS? Three different approaches (injections, patch, gel), hopefully at least one may work.

  49. Hi Ohad,

    Are you still positive about BOLD?

    There has been some insider selling from May to July of this year by CEO and SVP Chief Med. Officer in the range of $38-45.

    Thanks.

  50. Hello Ohad,

    It seems that resolving the c486 mutation for non-covalent BTK inhibitors may not work. The PLC gamma mutation is another problem that develops downstream. So there will likely be a need for a third generation BTK inhibitor. Moreover, this may also point to one of the potential flaws of targeted drugs: while they work in the short/medium-term (Ibrutinib is a good example), they can lead to resistance and mutations, and become ineffective.
    Any thoughts on this–I know you are quite big on targeted therapeutics?
    Thanks!
    Dan

  51. Adam |(XENE) – Honestly I don’t understand this move… don’t see a lot value there given Potiga’s issues, pricing challenges.

    Jinyu (ARWR) – That’s an impressive recovery! Not an expert on HepB so hard to say…

    Jaime Allen (FIXX) – Agree, very intriguing approach, applicable for multiple pediatric indications, I wish they would have published more because up until now I haven’t seen a lot of supportive experimental data showing they can edit liver cells in animals (note their 1st program is standard AAV gene therapy). Their vector looks super efficient based on what they published. Agree such a technology could avoid issues associated with nucleases and strong promoters. Key question is efficiency as HR is a rare event.

    Josefb (NITE) – Agree NITE isn’t cheap but it is a P3 company (choroideremia) and has several other programs so I thought they should be part of the GTx basket.

    Liang (ARWR) – sorry not very familiar with HBV.

    Kekse – Yes I am looking to add more shares. Currently the one on top of my list is AVRO. With VYGR and NITE I m still on the sidelines.

    Roy – Thanks!

    andre (FCSC) – I think I am scheduled to meet them next month, need to understand their data better.

    Anna (BOLD) – Yes, still positive on their XLMTM data whoch aren’t perfect but still encouraging. They also have a nice emerging pipeline.

    Dan – Yes resistance a primary issue with targeted therapies which means we should try to be one step ahead in this arms race, similarly to the dynamics with antibiotics.

    Ohad

  52. Ohad

    ECYT. News from the FDA that rPFS is a alternative endpoint and can possibly push up the approval timeline almost a year as well as a 175m secondary announced after the close.How do you view the regulatory update and does this news from the FDA increase the likelihood of approval and in turn make them a more attractive candidate for a possible BO?

  53. Agtc

    Why does the market hate Agtc so much? Still Trading under Cash value although they have multiple GT programs. When Could the sentiment change ?

  54. Hi Ohad,

    Interesting transaction announced for XENE to buyout 39.6 million of milestone payments and all royalties owed on future sales of XEN1101 for 6 million up front. Any thoughts about why they would do this now? Possibly stronger position for future partnership negotiations? Thanks!

  55. Ohad

    You had mentioned a couple weeks ago that additional weakness in EXEL may present a buying opportunity. The stock is down close to 8% today, due to PFE/MERCK-KGaA drug shows better PFS than Sutent monotherapy in 1st line RCC. Is the selloff warranted?

  56. Ohad,

    Happy healthy New Year! Quick question on ECYT. I noticed in the recent prospectus the have to pay royalties starting at mid teens not to exceed mid twenties. This might suggest they in reality own only half of this asset. Based on this, does that suggest the upside might not be very attractive from the price of the secondary offering 18.50. Thank you!!!

  57. Hi Ohad,

    Will appreciate your thoughts on PGNX following its recent failure and announcement of acceptance of AZEDRA for radiotherapy. Also on the continued decline of EXEL. Thanks for all your guidance.

  58. Ohad,

    What are your thoughts in general on high dose gene therapies? I’m seeing quite a few new therapies that are as high as 10^15 in certain heavier patients where the therapy is weight based (vg/kg) delivered locally either IT or through other targeted delivery. Where do you stand on this and do we have enough data to date to suggest 10^15 is safe enough?

  59. Hello Again Ohad……. I would be VERY interested in your take on the RADICAL price fluctuations in RGNX !??

  60. VKTX – nice data, especially safety
    Actually Nash was not its main focus; the primary endpoint was change in LDL-C, and with only 20% reduction they failed in that. The Nash-relevant endpoint was exploratory, and they hit the jackpot in that indication.

  61. Hi Ohad,
    Congrats on VKTX
    What do you think about MDGL falling following this news? Is this justified?

  62. Hi Ohad,

    What is your take on OMER? The drug 721 bagged two BTD in the last year also. What is the potential market size for the 721?

    What are the potentials for their other pipeline assets such as PDE7, PDE10, and GPCR platform? They claim that they strong IPs on GPCR and potential applications in CNS.

  63. VKTX: once again, congratulations on a good nose. At first glance, the VK2809 data is even better than the MGL-3196 data. Does VKTX still have catch-up potential? VKTX (1.2b$) vs. MDGL (3.2b$)
    In addition, what are your prospects for the NASH ph3 candidates Eflafibranor/Genfit (ph3 interim: 2H19) and Ocaliva/ICPT (ph3 interim:1H2019)?
    ICPT (3.6b$) vs. Genfit (0.74b€) –> Genfit appears cheap.

  64. Hi Ohad,
    Do you think if the TSRO’s lung caner development plan (PD1+Parp or PD1+TIM3) has a good chance to succeed?

    TSRO presented the combination data for Niraparib and Pembro. In the 1st NSCLC (PD1 naive), 9/14 showed response (both confirmed and unconfirmed) and all exhibited tumor shrinkage. Do you think if the signal real or just another IDO story?

    Regards
    Liang

  65. Hey Ohad,
    Nice early surprise with VKTX results! Been an investor since the $2s. What now? Do you think they are likely to get bought ahead of MDGL – similar to what happened with Ignyta (which was bought before Loxo because it was cheaper?).
    CEO clearly stated they are open to what’s best for shareholders. Gap with MDGL is $1.4-1.5 billion? (MDGL has 500M cash) could that be the floor to a BO target price? About $3B?
    Thanks!
    Dan

  66. Hi Ohad,

    I wonder whether you have an opinion on TOCA, 230M Capital, phase 3 on brain cancer, breakthrough therapy awarded. Bought some, will add more with your endorsement.

    Thanks a lot!

    Jinyu

  67. Ohad

    It’s been awhile since you spoke about SAGE. The stock has been meandering the last 9 months since its explosive move at the end of 2017.If I remember, you were most excited about the prospects for SAGE-217 and it’s many potential indications. Anything you can add at this time as they have moved this compound into Phase 111 for postpartum depression. Are you at all impressed with Brexanolone for the same indication or do you think SAGE-217 offers better potential for women who suffer from this disorder. Would you add to your position or take a wait and see at this point

  68. After acquisition of gene therapy portfolio of ten clinical and pre-clinical stage AAV programs in neurologic lysosomal storage disorders, Amicus now is a gene therapy play.

  69. FOLD became overnight a GT company.
    They acquired 10 programs, 2 in clinic.
    What do you think of the new focus into GT? Does it make FOLD attractive to follow?

  70. Hi Ohad,

    AVRO gained 25% since you said it was on the top of your list. Any guidance on valuation will be much appreciated. Thanks much!

  71. Afmd

    Do you like them After the Roche Deal? Many interesting programs and also owning 18,5% of amphivena which also has a program that could create value

  72. Ohad

    Does the disappointing results PGNX saw in its radiotherapy imaging agent 1404 for prostate cancer make you rethink your bullish stance in ECYT? The stock has traded slightly lower since the PGNX news

  73. Dave (ECYT) – It’s a clear positive but I don’t think it changes a lot long term. In prostate cancer I still expect physicians to rely on OS especially in 3rd line patients who are being enrolled.

    Sweeeb (AGTC) – I guess the answer to all questions is clinical data. So far the company generated disappointing results but positive XLRP data could definitely change the sentiment. Problem is nobody knows what to expect in terms of timelines and efficacy readouts, MGTX should data soon which could provide a framework for analyzing data in this indication.

    Adam (XENE) – I think the deal makes a lot of sense, now that they have the money. Easy decision IMO as the drug has a high likelihood of success and a sig commercial potential.

    dave (EXEL) – I don’t think the selloff is warranted, especially not until we see actual data and most importantly survival data, which may indicate whether combination treatment is better than sequential treatment. Regardless, cabo should still be used as a 2nd line as it has been proven to work following 1st line TKI. In any case, valuation is still a little rich with a market cap of ~5B.

    Ben (AVRO) – Given the recent move those plans are on hold for now. 500M per patient is too much for me although I really like the company.

    Scott (ECYT) – Thanks. Yes, royalties are meaningful but so is market potential so I still think the stock has room to climb.

    Les –
    PGNX – Need to look into that. Efficacy in the label doesn’t look that great compared to other radiopharmaceuticals.
    EXEL – See above. I think that at some point EXEL will become attractive again as cabo should have an important share in RCC either as a 1st or 2nd line treatment.

    Nick – >10^14 doses have been given only to a handful of patients systemically (at least based on reported literature). Not familiar with studies giving these amounts IT, sounds a lot….

    Bouschka (RGNX) – Actually, I don’t think they are so radical for a development stage biotech. A lot of potential but also risk and uncertainty…

    Christian (XENE) – Honestly I don’t, I see a lot more potential issues than upside.

    andre (VKTX) – Safety profile looks surprisingly clean. Validates TRb as a target, small sample size though…

    Aviv (VKTX/MDGL) – Thanks. I think it’s actually good news for MDGL, which still has a decent market cap. Too early to pick a winner.

    Liang (OMER) – Sorry, don’t have a concrete opinion there.

    Rüdi (VKTX/MDGL) – Thanks. It’s very hard to compare the two drugs right now, I plan on keeping both stocks. MDGL is further ahead so valuation gap is justified to some extent. Regarding other NASH stocks, not an expert there but I personally now very excited with the other players. ICPT’s drug is clearly active but there are better next gen FXR in development IMO so I don’t think it will be a major commercial success.

    Liang (TSRO) – I think it’s highly speculative and I would wait for more data.

    Dan (VKTX) – Very hard to speculate in these cases, especially given the high valuations for both companies and the limited data sets.

    Jinyu (TOCA) – Not a big believer in their approach. Clinical data unconvincing imo, hope I am wrong…

  74. Dave (SAGE) – Yes I still like the story and think 217 may be a better drug not only because it’s orally bioavailable. For severe PPD, I definitely see Brexanolone as an important treatment option, where hospitalization is not a major issue. No plans to add in the near future.

    Rob (LPTX) – Not very familiar with the story.

    Ryan –
    INFI – Not a big believer in their lead program.
    KRYS – Very speculative but plan to keep a small portion.
    GNCA – Haven’t looked at them for a while, supposed to meet management so will leearn more then.

    Alex (FOLD) – Right, and the portfolio looks differentiated with Brian Kaspar. Definitely worth taking a look, valuation isn’t cheap…

    andre (FOLD) – See above. I think it definitely makes them a more interesting company now. Valuation is high and debt is an issue but stilll…

    Les (AVRO) – I think I’ll, simply too expensive imo.

    Sopran (AFMD) – Deal was very impressive but I still don’t see the value there.

    Dave (PGNX) – I don’t think it has any read-across to ECYT. Different applications and agents.

    Ohad

  75. Hi Ohad

    ADVM yesterday declined on a good news, any explanation for the anomaly?

    Under what circumstances do you meet GNCA?

    whan are you planing to publish a new post?

    Thanks
    Alex

  76. Hi Ohad,

    Any thoughts on MGTA? Their valuation is relatively low (compared to current IPO’s). Beyond transplantation, it seems some programs could extend into other areas such as after reading AVRO’s S-1/publications it would seem these lentivirus companies could benefit from a less toxic conditioning regimen as well. They’ve guided to doing deals so perhaps they could minimize dilution until they become revenue producing.

    On another topic several people on my twitter stream talk of a GT bubble. While certainly many (smaller) companies are entering and some poor choices in programs, I don’t agree. FOLD recently acquiring 10 programs seemed extremely cheap (far from bubble prices) and the potential to produce dramatic efficacy such as seen in SMA, DMD (granted small n) and Luxturna. The impact in some disease areas, particularly monogenic diseases still seems quite a large opportunity. I compared it to Biologics maybe 25 years ago. The technology seems only in its early stages too. Better vectors and avenues toward retreatment are still in their infancy. I’d say we’re more like the 2nd inning than the 9th. Sorry for the rant, I would really appreciate your opinion on this!

    Thanks as always for your thoughts and a great blog!

    Maurice

  77. LPTX – curious why you are quiet on it? Before (last year etc) it was a conflict of interest so understand why you couldn’t talk about it. Now it’s no longer a conflict of interest with your regular job but still no comments. Per this blog, you are very intelligent and open to a lot of conversations and a lot of drugs spanning a lot of different fields. You do a lot of DD and there are very few stocks people mention in this blog that you completely just say “no comment” or “no idea” and don’t eventually look into. I wonder why LPTX seems to be one many continue to ask about but you remain so quiet/hesitant on…
    Am I really over-analyzing this? lol

  78. Ohad

    Would the ENTA compound be a next gen FXR drug you would consider to be more effective than the ICPT compound ? If not do you care to share who you think has a better FXR drug in development.

  79. Hey Ohad!
    Any opinions on what some are calling “Blow out” results for AMRN? ESPR going down today – people seem concerned.
    And what about NITE results? Did you have a chance to review? It seems that investors reactions are muted. RGNX recent results in wAMD weren’t that convincing (in my opinion) yet the market did not react too badly. Same with ONCE. It seems that the market is giving a pass to many of the GTx companies, and I wonder if this is because investors are having a hard time interpreting the results. When the old AVDM (Avalanche at the time) failed wAMD results two years ago the stock imploded losing 80-90% of its value. Maybe this is a sign that we have neared a bubble. Even so-so results are shrugged off.

    Dan

  80. Hey Ohad,
    Also, MGEN at a new low, it seems – market cap just $110M. Seems intriguing given the broad application of their platform and the number of candidates in development, including ph2. I have added to my position today.

  81. Ohad
    I am a bit puzzled why ESPR is down on AMRN data. AMRN had reduction in CV risk for pts. with well controlled LDL-C, what ESPR drug is doing. So I guess neutral at worst.

  82. Ohad
    NTGN and GNCA both have neoantigen vaccines in Ph 1.
    You said that you don’t like vaccines, so I don’t expect comment about that

    However both have neoantigen T cell therapies, which look quite interesting
    NTGN has an edge here – they are already planing Ph 1 in solid tumors.
    While GNCA program is still in discovery.
    Both companies claim advantages compared to CAR-T, TCR, TILs…
    Does the approach make sense?
    Any preference / comment about both companies?

  83. Alex –
    ADVM – If you are referring to the fast track designation, I don’t view it as significant.
    GNCA – I meet/speak with companies on a regular basis.
    Hope to publish something early Oct.

    Maurice (MGTA) – Still on the sidelines there until they generate more convincing data. I like the approach and the field deserves some progress but hard to interpret their data. Valuation is still generous for this stage IMO.

    GTx – While I don’t think there is a bubble in gene therapy, these companies are benefiting from the overall market conditions which are very strong and create unreasonable valuations in some cases imo. It would be fair to expect cycles in every field although I agree that the trajectory is still positive with so many monogenic diseases to treat. I also thought the FOLD deal made sense.

    Sword (NITE) – Still didn’t delve into it, plan on hearing their webcast soon. The lack of dose dependence is troubling at first glance but that may be explained.

    Kay Lee (LPTX) – Perhaps it’s just over-conservatism from my end but given the historical context but I prefer to keep my day job and this blog as separate as possible. Regardless, it’s hard to track the entire bio field with so many public companies so there are a lot of stocks on which I don’t have a strong opinion.

    Dave (ENTA/ICPT) – Yes , among others. As I wrote, not an expert but there are many programs in development including some private companies. Don’t have one I consider better than the other.

    Dan (AMRN/ESPR) – Blow out indeed. Good for them, I never thought it would end up as a success. I am less concerned about ESPR given the different pt populations (The AMRN study excluded pts with high LDL which are exactly the patients ESPR are after).
    NITE – Not yet, will check.
    RGNX – I thought they are on the right track but still too early, at least they have dose dependent protein secretion.
    In general, I do’t think there is a specific GTx bubble, part of the overall market conditions.
    MGEN – Agree it’s interesting with some clinical poc. Not a big fan of their indications though…

    andre (ESPR) – Agree. Maybe not neutral, as there may be an overlap in real life but there is always the possibility to combine.

    Alex (ABEO ) – I still view it as a long term core GTx holding.

    andre (NTGN/GNCA) – I am optimistic about cell therapies for neoags, makes a lot of sense but also tricky from a logistics perspective. Definitely an area to follow.

    Ohad

  84. Hi Ohad,

    Saw an article that said that at a high level VKTX had the best performance/safety data across ICPT/MDGL & VKTX. Was surprised to hear that VKTX’s drugs were licensed from LGND. And MDGL’s from Roche. No wonder LGND stock has also scaled new heights. Can this be a factor in VKTX and MDGL valuation? Do you have any comments on ICPT (closest to market) v/s MDGL and VKTX?

    Welcome comments from fellow bloggers.

    Ohad – really appreciate your sharing your knowledge and doing it in such an amiable way. Thank you.

  85. Ohad
    do you have an opinion about CERC.
    They have NMDA in Ph1/2 – NR2B selective (from MRK)
    Plus 5 preclinical, incl one for partial onset seizures – Ph 1 ready(?) (from LLY).
    Not expencive – only 160M, but not a lot of cash.

  86. Ohad
    NGM S-1 is published. What do you think about their NASH approach – engineered human hormone FGF19. Initial data look nice – they even reported fibrosis reduction in 42% of the pts, 60% ALT reduction

  87. Hey Ohad,
    Do the AMRN results warrant a rethink of LDL lowering theory?
    after all, PCSK9 almost failed to reduce cardiovascular event (relative to AMRN).
    And what are the implications for ESPR – and companies like MDGL and VKTX (or even NGM- interesting story how Merk invested in them early stage $700M) whose drugs greatly reduce triglycerides.
    Dan

  88. ohad

    AVRO. The stock has sold off over 40% this morning on news regarding data on AVR-RD-01 in Fabrys.You had mentioned last few weeks that you had the stock on your buy list but that the valuation was too high. Have you had a chance to look at the data, and does this selloff give you a opportunity to add this stock to your portfolio?

  89. Avro:
    wow… down 50%. Results seem to lack durability and sample size is very small. Market cap is still quite high, even after drop, especially when compared to cos such as ADVM or AGTC

  90. Hi Ohad, Dan,

    Read AVROs release on the results and it shows (measured levels) that the treatment was effective – to the point that the patient was taken off ERT. Dan – Not sure why you indicate otherwise. Am I missing something?

    Similar behavior on OMERs results. They were also positive with 50%-60% efficacy and yet their stock dropped and Adam Feurstein called their study a failure (just because after 12 weeks – the initial dosing period, the study and placebo arms were both at close to 18%). Would appreciate your thoughts on this.

    When does AGTC provide a readout?

  91. Hey Les
    OMER?
    I have not followed them but the little I just read seems that the placebo also had 50% efficacy…. so if that is the case, the study failed completely.

  92. Hey Ohad,

    Have you had any chance to look at the VK5211 ph2 results – more data were presence this week. GTXI failed miserably, but VK5211 has show dose response plus seems to me much more efficacious in building lean muscles than the GTXI drug (9% increase compared to 2.5%). Also, shares are down to $15.20 compared to a recent high of $24, while they NASH drug has been derisked some. Wondering if it makes sense to add some shares on the correction. Any opinions, especially on any value of their muscolosketal SARM program? And what do you think of their rare indications strategy for Glycongen storage and X-ALD, given the NASh readout?
    Thanks as always for you insight!
    Dan

  93. Les (VKTX/MDGL/ICPT) – Recent data clearly put VKTX at the forefront but not sure anything can be inferred beyond that based on cross trial comparisons, sometimes with small sample sizes. I am not an expert in NASH but my preference is to go with MDGL/VKTX rather than ICPT.

    andre (CERC) – It’s hard for me to reach definitive conclusions on many of those NMDA programs, hard to assess without robust clinical data. Not familiar with their other programs.

    NGM – a very interesting program with broad metabolic effect beyond NASH, metabolic FGFs look like a very promising class, they definitely stole the limelight at EASL earlier this year, data is provocative especially due to the fact they saw an effect after only 8-12 weeks (but sample size was very small). The drug was injected daily, which is a major issue, so not sure it’s a viable product.

    Dan (AMRN) – I don’t think the data raise doubts about LDL as an important driver for CV events, it identifies another paralel (potentially complementary path). Agree it creates a high bar for TG lowering therapies but the drugs you mention have broader spectra of effect.

    dave (AVRO) – An absolute disappointment…. Very hard to stay excited after seeing the graphs for pts #1 and #2, the current protocol doesn’t look viable so even if they optimize it (conditioning, viral transduction) , it will def take time.

    Dan (AVRO) – Agree, expensive even after the drop.

    Les (AVRO/OMER) – You are right, the respective PRs paint a positive picture but if you look at the data they are underwhelming. For AVRO, pt#1 is indeed off ERT but expression is decreasing at an alarming rate, so is the viral transgene.

    Gene H. (ONCY) – I am still on the sidelines regarding oncolytic viruses. A lot of activity especially on the private side but so far TVEC is the only proven one and commercial success is limited.

    Dan (VKTX) – Honestly did not spend a lot of time on these programs, focused more on the Tb program.

    Ohad

  94. Hi Ohad,
    I know you got out of TRVN but looking at recent reports what is your expectation on the Oct 11 review with FDA? The stock has doubled over last few weeks to $3 and analysts are projecting a PT of between $7 & 15 with Buy recommendations.

    Welcome comments from fellow bloggers who are holding & following TRVN.

  95. Les – Buying, following for nearly two years – If approved, the FDA label could be a binary event in itself. Broad label is needed for 2nd Qrtr (19′) earnings, hence the one year targets of $7-15.

  96. Hi Ohad,

    Do you have an opinion of ACST, it seems to be a cheaper version of AMRN, currently only 50 mm cap comparing to almost 5 billion of AMRN. Its 3-omega fatty acid drug from krill oil is currently in 2 phase 3 trial. Your opinion is highly appreciated.

    Jinyu

  97. Hey Les,

    I bought TRVN shares a couple months ago and I am holding for higher gains. As mentioned before here the (risky) migration program is also heading to ph2, and that could be a wild card. Moreover they have been out licensing right to their drugs to asian markets and generating some cashflows. But valuation will depend on the cash burn and commercial execution, which is hard to predict and risky. Just look at SGYP – though they are promoting to a larger market with against a strong incumbent AGN. Maybe TRVN can do better given they are competing against generic morphine and for some older, at risk patients, the slight decrease in SE (and relative low price of the drug) might be enough to win some marketshare.

  98. Hey Ohad,

    What did you think about BPMC/LOXO RET updates today. Both data sets look pretty remarkable to me.

  99. Ohad
    What do you think about ORTX –
    Autologous gene therapy biotech Orchard
    IPO F-1 is just published
    The pipeline looks impressive.

  100. Do you see a paralel to 2015/2016 with the recent drop in stock prices Where you added to your BIS Position?

    And Do you think biotechs are in a bubble or do we just have a Short correction?

    Thank you

  101. Sad news all around. Biotechs are under pressure and bad news on TRVN and AFMD. At such times one laments about the long term buy and hold approach. Hopefully better days are around the corner.

  102. VKTX – Had mentioned earlier that LGND has licensed the drug to VKTX. Saw from insider trades that LGND sold 252,000 shares end Sept at $19 but still holds 6 Million shares. An input to help model holding patterns :-)?

  103. Hi Ohad,

    Had a question on XENE. In your analysis of it you indicated a valuation of $450-550M. Was that at the time you penned the analysis? They have a catalyst coming up in November – if that is positive what would it do to the valuation. Analyst consensus PT is currently $15. Nobody seems to be indicating a higher PT right now. Would appreciate your thoughts. Thanks.

  104. TRVN – had you a chance to review the AC documents. What do you think, is there a chance for a positive vote? Maybe a 5:3 at best? Ive bought some cheap shares today. Maybe its a mistake but I like this kind of binary events!

  105. Thank you for all your helpful posts and comments Ohad. They provide a lot of learning opportunities.

    NITE: I skimmed the Sept 22 press release. Looks to me perhaps this is the “explanation” for the weak dose response?
    ‘ Mild drug-related inflammation that potentially dampened efficacy was seen in the treated eyes of cohorts 4-5, with treatment efficacy observed to have been rescued in patients who received additional steroid treatment. ‘ How do we know or estimate how successful NITE will be at handling drug-related inflammation going forward?

    Oct 9th’s NITE stock price drop is mostly due to institutional selling? Their stock price pattern doesn’t cluster as well as their peers’. Not sure of reason.

    Any idea which (date) AGTC dataset this refers to? Wells Fargo analyst Jim Birchenough claims AGTC shows stronger gene expression [than NITE’s] in XLRP. Gene expression as measured by ?microperimetry? Anyone?

  106. Les (TRVN) – The briefing docs are quite harsh and discouraging for a product that had a questionable profile to begin with imo.

    Bouschka (CTMX) – Too expensive imo without clear clinical poc.

    Jinyu (ACST) – Sorry, don’t know it well.

    Dan (BPMC/LOXO) – Agree, remarkable efficacy and duration looks strong. I think LOXO’s drug has a superior safety profile.

    andre (ORTX) – I like the company and technology but expect valuation to be a barrier here.

    Sehrlang – Generally speaking I think the markets and the biotech segment are facing an imminent correction after a decade bull run. Timing and magnitude are impossible to predict imo. I don’t think biotechs are in a “bubble” but valuation for many biotechs don’t make sense to me, especially the early stage ones.

    Les (XENE) – I try to avoid short term price predictions, prefer to look at long term value proposition and for XENE it is still intact IMO with two agents with potential in the general population and respective niche indications, each representing a 500M potential with conservative assumptions.

    Rüdi (TRVN) – Very discouraging review, would be tough to approve this drug imo.

    BioDC (NITE) – Yes, that’s definitely an option and we know inflammation towards the capsid could impact in transgene expression but it’s just a hypothesis for now, Need to wait for additional patients with prophylactic immune suppression.
    Not sure about AGTC, perhaps he was referring to animal data. I don’t think there is data to include anything about protein expression in humans…

    Ohad

  107. Ohad,

    AXON – I see that they will be presenting some data at ESGCT soon on their new gene therapies. I don’t believe their gene therapy assets are valued into the stock right now and it seems like a great time to buy. I know the company and stock has a riddled history, but it seems like they are reinventing themselves. I’m curious to get your thoughts on the company.

    Nick

  108. ARGX / MOR

    Do you Follow european Biotech companies and do you like the mentioned ones at current valuation?

  109. 1. Ohad…did u ever get to meet with Fibrocell?

    2. Any other gene therapies u like bio post dip?

    3….also…r u watching $alpn?

    Thanx Brother

  110. Ohad, Nick,

    FCSC – Have been looking for Ohad’s feedback on FCSC as well. Just one analyst has put a price target of $22 on it and there are some October meetings that they have scheduled. Interestingly while Randal Kirk (CEO of FCSC) bought 6000 shares of FCSC at $2 he also bought 6 million shares of XON (of which he is CEO) for $100M sometime ago. XON’s subsidiary is partnering with FCSC on the development of its drug/pipeline. XON is quoting $15 right now with a PT of $27 and 52 week H/L of $20/10.

  111. Hi Ohad !

    first of all thanks for all the info of this website. Great job, really appreciate.
    AVEO: results of TIVO-3 in the next 4 weeks.
    I think shd be positive (PFS and OS) compared wiith current treatments (Sorafenib etc…). Fotivda already approved in EU/EMA.
    AEs of Tivozanib better than other drugs.
    Negative lines:
    TIVO-3 didn’t reach the 255 PFS events, why?
    HR will be less than 1 ?
    Difficult to evaluate Eastern Countries Sites.
    I wld really appreciate your thoughts on this trial. Thank you
    Bruno

  112. $ALLO – $420mil raised and IPO with $2bil (actually $3bil at time of this post) valuation all within 11months!! Thoughts on this (and CAR-T)? That valuation gap with $CLLS is bit wide…

  113. Ohad,

    AXON looks interesting, but they are burning about $60 million a quarter, so they’ll need a big raise very soon. What do you think?

    Are you still bullish on KURA? What’s going on with them?

    So you see any hope for TRIL? The stock is dirt cheap.

  114. Ohad
    UCART19 will compete, if approved in 4-5 years, with 3 CD19 autologlous CARTs which work well. In general, what could make the autologous approach viable?
    Is it enough to prove non-inferiority to excite investors / doctors?

  115. I like AXON, too, but their cash position seems precarious. They burn cash like crazy.

    Ohad, TRIL has gotten dirt cheap. Do you see value there?

    Are you still bullish on KURA? What is happening with them?

    Do you see any value in ADXS at about $.75/share?

  116. Nick (AXON) – Agree it bears watching despite the checkered history given the low EV. Still not sure about their Parkinson’s program, I am more interetsed in the C9orf72 program which is still early.

    Kagawa (ARGX/MOR) – Yes I am following both, great companies but not sure about currnt valuations. If I had to pick I would go with ARGX because they have two proprietary programs with a fairly clear path to market.

    Robert goulet –
    FCSC – No, supposed to meet them next month.
    Regarding GTx companies – I like what FOLD are doing but valuation is too high.
    ALPN – Haven’t looked at them for a while, nice science from what I recall but they were quite early at the time.

    Bruno Fraschini (AVEO) -I am not following the story closely but PFS should be superior, it will be hard to demonstrate an OS benefit imo. There is no doubt tivo has a cleaner safety profile, could be important in combining TKIs with PD1, depending on how the Inlyta+Bavencio data. Hard to interpret the rate of events, can go both ways.

    Kay Lee (ALLO) – Agree, interesting gap.

    Richard Baker –
    AXON – 60M quarterly sounds very high, should be ~20M from what I understand.

    KURA – Yes, still holding, waiting for updated results.

    TRIL – I am not optimistic about CD47 as a target especially after the recent news about CELG’s program. Another IO disappointment….

    andre – Agree market is very competitive with next gen versions in development as well. An off the shelf product with no-inferior efficacy is an attractive value proposition imo.

    Richard Baker (AXON/TRIL/KURA) – See above on both.

    Ohad

  117. Ohad

    Any plans on a new write up?Thanks for lending some invaluable information to a individual biotech investor and helping to navigate a extremely volatile sector.

  118. Hey Ohad,

    I am wondering if you have an opinion about the new anxiety med that VTGN acquired (a pherin) and their hire of the Social Anxiety Disorder KOL as advisor for the phase 3 development of that asset (PH94B).
    Thanks

  119. Hi Ohad,

    Regarding KURA, what’s your opinion on the potential marker for Tipifarnib? HNSCC late line is small so i presume they will charge a lot but are they looking at something in the low hundreds of millions? What other indications do you think Tipifarnib has a shot in?

    Thanks.

    Rich

  120. Chris K (KRYS) – Still didn’t listen to the webcast, overall sounds encouraging but a very small sample size. The fact they were able to re-dose without any immune responses is very important.

    Dave – It’s always hard to find the time, will try to post something towards the end of the month.

    Dan (VTGN) – Wasn’t aware of Social Anxiety Disorder as an indication ,not familiar with that program.

    richard trent (KURA) – So far the only robust efficacy is signal is in H&N so that’s what investors should assume for now. Agree potential isn’t huge but still significant.

    Ohad

  121. Ohad, SAGE has a market cap of 5,7 billion, “not nothing” I would say. Is it well justified? What are the next catalysts?

    best regards!
    Christian

  122. Excellent call on ECYT. Congratulations to ECYT folks. #ohadrocks continue this great work whenever you get time. Always a treat to read your research and opinions.
    Major breakthrough still year(s) away, good buyout price for folks that believed in ECYT

  123. ohad nice work on Ecyt. you have your finger on the pulseman. Q about STML. continue to hold? do we have more upside? thanks.

  124. Christian (SAGE) – Agree, not cheap but the potential for a new depression drug with the clinical features that emerged from their P2s is so explosive I prefer to hold.

    Garry Xo/ DJ Chudasama/ Xavi (ECYT) – Thanks! Surprised it was NVS who acquired them eventually, premium isn’t huge but still a decent valuation.

    don (STML) – Thanks. Yes I still think there is upside, not huge but the potential is there.

    Ohad

  125. ECYT: Thank you so much for sharing your knowledge and science with with us!
    I highly appreciate.

  126. Ohad, Congratulations again! Fantastic analysis and timing on ECYT. Thanks much
    for sharing your expertise and knowledge.

  127. ecyt!! it was fast..
    SAGE – you like sage – 217 ? when the p3 ~ Is about to end?
    ~how explosive it can go?
    Thanks!

  128. Hey Ohad!
    Great job with ECYT! This. Has to be one of your quickest (portfolio purchase to acquisition). What do you think of valuation? NVS seems to be making a lot of innovative tech deals. Leading the way!
    Are you holding until closure? Do you think another company could outbid NVS?

    Thanks
    Dan

  129. Ohad
    I’m a small investor! This is the third buyout you have given me in a year (DMTX, AVXS and now ECYT).
    Thank You so much!
    Declan

  130. Ohad what is your opinion of $ODT who is is addressing breast cancer via novel low toxicity taxane. They ipo’d at $24 and have recent significant insider purchase at $19.55 of 90,000 shares by Kevin Tang

  131. Thanks Ohad for your great analysis. First buyout experience for me.
    Since it is all money does that mean i just have to wait for the money!?!
    Georges

  132. Hi Ohad,

    Terrific call on ECYT. Thanks for sharing your exceptional insights and knowledge.

    Do you think JnJ or Pfizer could come up with a higher bid, considering that (1) the prostate cancer franchise is already in place and (2) the $1-2 billion market potential you had mentioned at one point? Also NVS paid $3.9 billion for the previous radio ligand deal, with inferior efficacy. Maybe it’s the poor market conditions?

    Curious about your current take on NERV also. Thanks!

    Anna

  133. Hey Ohad,
    AMRN – what do you think will happen? Do you think AMRN is on the radar for an acquisition? Market cap is already $6 billion. Some people on the twittersphere think it can double or triple? Is there any merit to those views?
    Thanks a lot for your insight and perspective,

    Dan

  134. Ohad….. I know you can not comment on Arqule…..but is there a website or a blog that you could refer me too? Would welcome any comments from this EXCELLENT BLOG !!!

  135. A few editions back you were positive about CNS-companies.
    What’s your take today and more specifically, do you have an
    opinion on ACIU (AC Immune) and AXSM (Axsome)
    TIA

  136. Hi Ohad,

    Any thoughts on Immunogen’s updated Mirv+Pembro results from an expanded cohort?

    http://investor.immunogen.com/news-releases/news-release-details/immunogen-presents-initial-data-forward-ii-expansion-cohort

    It looks like out of 54 patients, they achieved 16 confirmed PRs and 9 unconfirmed PRs. (If they wanted to pull a “Clovis,” they would have said 46% ORR and been done w/ that.) Given that they presented the initial cohort at SGO in February, enrollment would only have finished in the middle of the year, so it’s likely some of those 9 with unconfirmed PRs didn’t achieve confirmation due to immature data rather than progression.

    Initial PFS is 4.2 months for the whole population but DOR was 6.2 months for the whole group and 8.1 months for the med/high FR-alpha expressers; so this is likely to improve as data matures as for the med/high group:

    “At the time of analysis, the data were immature with 16 patients still on study (all with medium or high FRα expression) and a median follow-up of 8.3 months.”

  137. Any insights into dementia/alzheimers drugs? This is a very green field area that hasn’t seen much break through. Any companies you are looking at for this? Any thoughts in general about dementia/alzheimers?

  138. Hello Ohad. I asked you in the past about ARRY (Array) trial results; however, would you consider owning it as part of your portfolio?
    They seem to have a large pipeline (at least 9 in ph3) with multiple trial partners and I believe a healthy cash balance. They also now have their first commercial drugs.
    I hope that you can shed some light on where they might be heading. Thanks again for your insights. You are the best analyst that I have ever encountered- definitely when it comes to Biotech.

  139. Ohad,
    What do you think about DCPH data?
    Nice durability but weak 4L data
    Is the sell off bc the market writes off their current Ph3 in L4?

    Great call on ECYT. Excpeciall “attractive acquisition target” was confirmed in about 2 months.

  140. Hi Ohad,

    KURA’s results were underwhelming – only 6 of the 20 (and 3 maore maybe) seemed to respond – report indicated that patients with allele frequency >20% (13 of the 20, of which only 6 responded) which responded to the treatment is only 5% of the patient population. Got out of KURA at breakeven :-(. Sad day for Biotechs today with IMGN & ADRO being badly beaten down.

    Any idea why VKTX is being draged down so badly?

  141. Les–Like you, I am very interested in Ohad’s take. I didnt think the data were that disappointing…looked like 17 pts on trial, 11 evaluable, and 9/11 with PR or SD. Only one patient progressed primarily on therapy. The 12th pt, evaluable after the study cufoff, is a near PR.
    We knew that this was a drug for only 5% of the HNSCC population–when I asked that question (November 13, 2017 on this blog) Ohad estimated that represented a 3000 pt subset.
    Appreciate as always the insight of this group and of course Ohad….best blog on biotech that I have ever seen!

  142. Ohad
    how big of a concern is that VKTX has composition of matter protection only until 2024. Some method of use patents are much longer though
    Do you know the patent situation with MDGL?

  143. Ohad

    The market had a negative reaction to the data from NTGN. Does that change your positive outlook you have for cell therapies for antigens, or was that specific to NTGN. Are there others in the field you think are worth following?

  144. Ohad
    ORTX IPO Oct 31. According to F-1A the market cap will be 1.4B at $15.
    You said that you expect the “valuation to be a barrier”
    Is 1.4B too high, considering they have an approved drug in EU (extremely rare disease), plus 5 drugs in clinic, incl 3 pivotal trails with potential 3 x BLA in 2020?
    Thanks

  145. ECYT – Thanks, everybody, for the kind words.

    Alex (SAGE) – The MDD P3 is expected to start shortly so we are talking about early 2020.

    Dan (ECYT) – Thanks. Agree about NVS, investing in emerging technologies with unclear business models so clearly deserve credit for taking the risk. I don’t know about another bidder but I plan on holding after DMTX…

    Paul Gathua (ODT) – Don’t kow them well but not a big fan of the approach.

    Georges Robitaille (ECYT) – Yes, or you can sell beforehand.

    Richard Baker (NERV) – I still think it’s attractive, a basket of de-risked CNS assets with readouts next year.

    Anna (ECYT) – I also thought JNJ is a more relevant buyer given its interest in radiopharmaceuticals and franchise in prostate cancer. I think the gap in valuation represents the fact that AAA was on the verge of commercialization and its platform capabilities.

    NERV – See above.

    Dan (AMRN) – Don’t know the field well so hard to say. Sounds like a lot of people are going to use it.

    Bouschka (ARQL) – Sorry, can’t think of a relevant website.

    rodolfo –
    ACIU – Not a fan of their clinincal pipeline, especially not with a 1B+ valuation.
    AXSM – Don’t know them well.

    wildbiftek@gmail.com (IMGN) – I think market reaction was justified, data weren’t exciting. Yes, some of the responses might get confirmed but still teh totlity of the data isn’t very encouraging given monotherapy data for both agents.

    Kay Lee – Unfortunately nothing I can think of.

    Lawrence (ARRY) – Thanks. Their BRAF+MEK combo looks differentiated so it could capture a significant market in BRAF+ melanoma and they are eligible for royalties from LOXO but at a 3B valuation I prefer to sit on the sidelines.

    andre (DCPH) – Agree data are disappointing and selloff was warranted. My feeling is that BPMC has a better drug but hard to compare across trials.

    Christian (KURA) – I find the data disappointing, there is still a clear efficacy signal but not as strong. Enriching patient population may take the ORR back up but with a cost of losing a portion of the market.

    Les (KURA) – Agree results are disappointing but I still think the drug is viable.
    No idea about VKTX.

    Gary (KURA) – Thanks. I agree the drug is active but stock reaction is justified given the drop in ORR. Yes, they could go for a narrower patient population but that means going down to ~2000 eligible patients in SCCHN.

    andre (VKTX/MDGL) – Not familiar with their IP status but obviously composition of matter is much stronger than other patents.

    Dave (NTGN) – I think the stock’s behavior represents market’s skepticism around vaccines for neoepitopes. The jury is still out on cell therapies targeting neoepitopes but I am still optimistic. There is obviously GRTS who recently went public as well as other private companies.

    andre (ORTX) – Yes, I think 1.4B is too high but I still like the company so will wait for a better entry price.

    Ohad

  146. Ohad
    would you like ACIU @ MC = 570m ( not 1B. !) a little bit more ?
    Agree on the Pipeline : Pretty one-dimensional

  147. Hi Ohad, fellwo bloggers,

    Any idea when in November XENE will provide an update on the trial results? With their earniongs conference call on November 5th?

  148. SNSS taking a big hit today (lately), i have not seen any recent statements or news leading to it. The price is now at a big discount to your original buy, is it a good entry

  149. Bubble or not, sad day for Biotech’s. Hopefully a boince tomorrow. MDGL is being decimated. Anybody know why? Folks who bought shares at $300 have gor badly burnt. Not sure why they are not stepping in and buying.

  150. Ohad…. Just realized that my post aboutMeiraGTx was on the Zenon Thread. You have viewed them in a favorable light… but they are not in your portfolio. Is the valuation too high or are you considering adding them to your “gene basket”???

  151. Ohad have you given a look at this morning infos coming from Eisai/Biogen on BAN2401 for Alzheimer (CTAD Barcelona)? The market reaction is negative on a upward day when the new data seems to me quite positive since it relatively clears up the questions around E4 unbalance in the study groups. They say they identified an even better response for E4 carriers (15% of the population but overrepresented in Alzheimer population) that they write was 68% (compared to their positive announcement at 30%) better than placebo!!! (slowing of cognitive loss). Since this is a subset very highly at risk already this group would be major…

  152. Just to add a few numbers. E4 is present in about 15% of humans but is present in 40% of Alzheimer`s patients. If you have E4/E4 you are about 90+% sure to develop it. Around 108.7 millions americans are over 50 years old which would be the time to start the treatment to prevent the disease to bring cognitive impacts. How many of these people (E4/E4: 2,8 millions, E4: 16,3 milions…) would want the treatment at 50 or 55?
    If it can show a 10-15 year delay it could make this disease almost disappear for the late onset group. There is a possibility for non-carriers that being less rapid decliners that it is going to be tougher to demonstrate it with the actual trial design. My two-three cents…

  153. Ohad…u mentioned u were interested in CRSP but valuation was too high….r u now inclined to add? ….also do u prefer it to NTLA or EDIT?

    Excited to say I added some ABEO ….i really like this gene therapy company since they have a strong focus on juvenile disease.
    They seem reasonably priced.
    R u adding more on this dip?

  154. RGNX

    any opinion about the P1 results for rgx-314 in wet amd? where do you see the stock heading in the next 5 years? Thanks :)

  155. Ohad

    Are you familiar with the ADXS neoantigen program that is partnered with AMGN. Do you see any value there?The stock appears to be trading at discount to its cash value.

  156. rodolfo (ACIU) – Right, my mistake, still doesn’t change my view on them.

    Les (XENE) – Not sure but they could provide an update as part of their earnings call.

    Roy (SNSS) – Not sure what’s going on there…

    Les (MDGL) – Not aware of a particular reason, looks like part of the overall market movement.

    Harold (BIS) – Yep… and I am adding more today in my next update, I think this is just the beginning…

    bouschka (MGTX) – I think they have a broad pipeline which is still quite early, definitely on my watchlist, waiting to see clinical data.

    Alex (ESPR) – Perhaps, can also be nervousness before Study 2 data next week.

    Georges Robitaille (BIIB) – Not an expert here but the analyses they have done looks fishy to me, I don’t believe Abeta antibodies work in AD.

    Robert goulet (CRSP/NTLA/EDIT) – I still prefer to wait until they have data or price goes down significantly. Usually, such technologies take a lot of time to mature and to me it still feels like we in the hype stage of the innovation cycle.

    ABEO – If they continue to decline, would definitely add more.

    qualio (RGNX) – Data look positive, at least in terms of protein expression as they have clinically relevant levels after 6 months.

    Dave (ADXS) – I don’t believe in cancer vaccines even in the context of neoAgs so I don’t see a lot of value there, hope I am wrong…

    Ohad

  157. ONCE / SGEN

    do you these stocks are reasonable priced or cheap after current correction?

    CTMX

    Do you like the data which was presented at ESMO? It looks like that the masking technology is working and stable. Responses were low due to the tumor profile but that is ok. the side effect profile looks good, esp. in combination with ipi and at higher doses. whats your take? also price came down a lot…

    ZYME

    seems to be really undervalued . they have already presented good data and have a nice pipeline / good partnerships which will produce new value soon. do you plan to add more?

    Thanks for your work !

  158. BIS

    i agree with you that the correction will go on and NBI / XBI will decline. no one can predict how far the correction goes, because imo many stocks are already undervalued in biotech and not too expensive. also the biotech field will have possibly many growth driver with gen / cell therapy / RNAi etc. in the future.

    So how much BIS will you add in % of your portfolio? Thanks

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