Investment ideas for 2019

Despite the recent surge in general and biotech indices I still believe we are in the beginning of a significant correction after a 10-year bull market. If a major correction occurs in 2019, I intend to use it and increase exposure to small cap biotechs as I still believe in their long term value proposition.

With respect to stock picking, the thriving biotech IPO market created a dichotomy. On the one hand, investors have a lot to choose from as the IPO class of 2017-18 includes so many high quality biotech companies. On the other, valuations for many companies (especially the ones without clinical validation) appear to be overblown, driven by hype rather than data.

The most extreme example is Moderna (MRNA), which went public with a valuation of $7.5B without a single program that has a clear route to the market. Many other companies IPO’d with generous valuations (>$500M) without clinical data, sometimes without a drug in the clinic. These include Rubius (RUBY), Arvinas (ARVN), Editas (EDIT), CRISPR (CRSP), Intellia (NTLA), Jounce (JNCE), Denali (DNLI), Homology (FIXX), Wave (WVE) and Scholar Rock (SRRK).

Looking at recent IPO filings, not a lot has changed. Synthorx (THOR) whose lead IL-2 variant is not yet in the clinic, is worth $431M. The same goes for high profile imminent IPOs: Harpoon (Lead program in P1 with limited data and no efficacy signal to date), TCR2 (lead program about to enter P1) and Alector (2 programs in P1, no data in patients).

These high profile companies have excellent fundamentals and could eventually generate huge returns in the long run but given the industry’s high attrition rate in translating preclinical data to humans, I find their stocks outrageously expensive. I therefore prefer to wait for clinical data before buying any of these stocks even if it means a higher price because, judging by the history of our field, most of them will encounter setbacks and failures.

Another group of stocks on my watchlist are advanced stage companies with clinically validated assets and in some cases regulatory approvals that are traded at a reasonable EV. These include: Xenon (XENE), Insmed (INSM), Chiasma (CHMA), Stemline (STML) and Esperion (ESPR).

Regardless of market performance, 2019 will have a flood of clinical data. Here are some segments worth tracking.

ANTIBODY-DRUG CONJUGATES (ADCs)

ADCs were the big hope of the antibody industry 5-7 years ago but so far did not live up to expectations. Originally, ADCs were supposed to combine the best of both worlds: chemo-like efficacy with antibody-like safety. In reality, ADCs behaved less like antibodies and more like chemotherapy with the main hurdle being off-target toxicity which limited the dose patients can be given. There are obviously additional issues specific for each program but a narrow therapeutic window has been the primary hurdle with many ADC programs to date. There were cases in which ADCs demonstrated a favorable clinical profile (HER2, CD30) but these are the exceptions.

Despite the challenges, 2019 could be a turning point for ADCs thanks to new technologies and a couple of “old school” programs that were able to generate compelling data.

Immunomedics’ (IMMU) Trop2 program (sacituzumab govitecan) has already been submitted for approval in triple-negative breast cancer. This program is very interesting because it relies on an old, less potent chemotherapy agent (like 1st generation ADCs which failed) but somehow Immunomedics found the right recipe with this program. Of note, this ADC is given frequently (weekly) at high doses (10 mg/kg), a regimen which is not feasible with 2nd generation ADCs from Immunogen (IMGN) or Seattle Genetics (SGEN). Efficacy to date has been encouraging (32% response rate, 6.7 months duration of response) and may be sufficient for accelerated approval.

IMUCSeattle Genetics’ (SGEN) anti-Nectin4 program (enfortumab vedotin) is currently in a pivotal P2 for bladder cancer. This ADC utilizes the same payload the company used in Adcetris (MMAE) which so far hasn’t been very successful in solid tumors for the reasons outlined above. With enfortumab vedotin, Seattle Genetics and its partner Astellas may have found the right target and indication to produce good efficacy even at a low dose (1.25 mg/kg). This agent still has serious side effects including fatalities that may be treatment related. The ongoing P2 is a single arm study in PD1-resistant patients with results expected in Q1 2019

sgenWhile many biopharmas de-prioritized ADCs (including Astellas recently), there are still a lot of smaller companies working on novel ADC technologies.

Initially, companies focused on highly-potent payloads, which looked great in mice but backfired in humans due to increased toxicity (see SGN33A as a recent example). Today, companies are focused on improving the therapeutic window by minimizing exposure in normal tissues, which is perceived as the main barrier.

It remains to be seen whether these new technologies improve ADCs’ therapeutic window but there is reason to believe some features can be optimized to overcome general toxicity. Personally, I am optimistic about Zymeworks (ZYME) and its ADC platform, which appears to rationally and meticulously address the major technical issues with ADCs. The company’s lead ADC, ZW49, combines the company’s ADC technologies including a bispecific binding region (to enhance cell penetration) as well as an optimized conjugation method (to improve exposure in the blood  while minimizing exposure in non-target tissues). ZW49 is expected to start P1 imminently and should have P1 data towards YE2019.

CRISPR AND PROTAC

2019 should have the first ever clinical data for two potentially disruptive technologies: CRISPR (clustered regularly interspaced short palindromic repeats) and PROTAC (proteolysis targeting chimera).

Editas (EDIT) and CRISPR Therapeutics (CRSP) both have active clinical programs that are expected to generate data in 2019. Editas is evaluating EDIT-101 in LCA10, a rare genetic retinal disease which is not amenable to standard gene therapy with AAV due to the size of the mutated gene. CRISPR Therapeutics is developing CTX001, an ex vivo treatment for Beta Thalassemia and Sickle Cell Disease, putting it in direct competition with Bluebird Bio (BLUE).

PROTACs are a novel class of molecules that selectively degrade proteins by harnessing the body’s natural protein disposal system. This could enable targeting proteins deemed undruggable with conventional methods. In principle, the concept is similar to siRNA but with a small molecule, making it more feasible in tissues outside the liver. Arvinas (ARVN) is expected to start P1 for ARV-110 (targeting androgen receptor for prostate cancer) in Q1 2019 and could have initial results by year-end 2019.

While both approaches are not validated in humans, any clinical proof of concept with any of the programs above will be huge news, potentially opening a new era in medicine.

IMMUNO-ONCOLOGY

The year has been particularly tough for IO pure-plays who went from the industry’s darlings in 2015-2016 to the most beaten down group on the stock market. This is easily illustrated by pure play IO stocks like Jounce (JNCE), Surface (SURF), FivePrime (FPRX) and Corvus (CRVS), all of which are currently trading close to their cash levels. Arcus (RCUS) is an exception with an enterprise value of ~180M.

There will likely be a lot of PD1 combo data in 2019 but so far nothing looks promising. Nektar’s (NKTR) PEGylated IL2 will have readouts from multiple studies but data will be hard to interpret without a control arm.

At ASH 2018, CD3 engagers demonstrated good efficacy in liquid tumors. Three CD20-targeting programs from Roche (mosunetzumab and CD20-TCB) and Regeneron (REGN) demonstrating good efficacy (including durable CRs) in NHL. Side effect profile appears manageable but toxicity is still an issue. Importantly, all agents were given once every 2-3 weeks, in contrast to first generation CD3 engagers (BiTE) that are given via continuous infusion over months.

Mosunetuzumab

CD20 TCBAmgen presented preliminary results for its CD3xBCMA BiTE in multiple myeloma, demonstrating responses in 7/10 patients. While preliminary, this type of activity may make bispecific BCMA antibodies (especially constructs with half-life extensions) a real threat to BCMA CARs.AMG420GENE THERAPY

2018 was not an easy year for gene therapy, a sector for which I still have high hopes. With a few exceptions, news flow has been negative to neutral dominated by development setbacks and early uninterpretable data. Muscle diseases provided a preliminary silver lining while ophthalmic and liver targeted programs failed to impress.

Early positive readouts in muscle diseases

Audentes (BOLD) and Sarepta (SRPT) presented positive data in XLMTM and DMD, respectively. Audentes’ AT132 data continue to look promising with significant improvements in functional and respiratory endpoints that cannot be explained by spontaneous improvement. As patients are treated early in life and their muscle tissue grows significantly, duration remains a key concern (in two patients there were mild score reductions at the last time points but it’s too early to tell whether this is a real trend or not).  The company expects to present updated results in 2019 and intends to file for approval if results continue to look good.

BOLD- ASPIRO

Investors got excited with Sarepta’s DMD data which were limited (4 patients) but did show impressive micro-dystrophin expression and sharp reductions in CK (a marker for muscle damage). The effect was less dramatic on key functional scores but improvement was seen across the different endpoints, including NSAA, which will probably be the primary endpoint for the pivotal study. Still, these improvements are hard to interpret without a control arm as they can be unrelated to treatment. Similarly to the case in XLMTM, DMD patients are children so the question of dilution as patients grow and add muscle mass is a very pertinent one.

Solid Bio (SLDB) and Pfizer are also enrolling patients in their respective DMD programs, with initial data expected in 2019. Results will be inevitably compared to those of Sarepta but they will likely be hard to interpret via cross trial comparison.

DMD GTx - From Citi

Source : Citi, November 2018

Pompe disease is the next frontier in muscle diseases with multiple programs in development, including Spark’s (ONCE) SPK-3006 and Audentes’ AT982. Both programs are expected to enter the clinic in 2019 with Spark taking the lead following a recent setback with AT982, forcing Audents to explore a different vector.

Liver programs generated mixed data

For liver-targeting therapies, 2018 will go down as a disappointing year. While hemophilia B programs from Spark and UniQure (QURE) generated promising data, Spark’s Hem A program continued to face challenges, leaving Biomarin’s (BMRN) BMN270 in the lead.

So far, companies could not replicate the initial success with hemophilia in other liver diseases.

Ultragenyx’s (RARE) DTX301 for OTC demonstrated suboptimal efficacy with only two of six patients achieving a response (normalized ureagenesis at 24 weeks). There was no dose-response despite a 3-fold increase in the second cohort, which is concerning. In 2019, Ultragenyx will provide an update from the third cohort.

The company recently released preliminary results from a second liver-directed gene therapy for GSD1, reporting clinical improvements (time to hypoglycemia) in 2/3 patients in the first cohort. The trial will start enrolling the second cohort imminently with potential data later in 2019.

Audentes’ AT342 in Crigler-Najjar syndrome also encountered setbacks due to slow enrollment and a transient biomarker effect in the first patient. The study is evaluating a higher dose with data expected in 2019.

Retinal programs

The retinal gene therapy space started 2018 with high expectations following the approval of Spark’s Luxturna (Dec 2017), however, the year included mainly mixed or negative data readouts.

Nightstar (NITE) presented first data for its XLRP program which demonstrated some efficacy signals at the lower doses but adverse events at higher doses required intervention which made data hard to interpret.

AGTC’s (AGTC) XLRS program failed to demonstrate efficacy, leading Biogen to terminate its collaboration with the company. AGTC has three other programs in clinical development, data from which are expected during 2019. Expectations around the two Achromatopsia programs are low given setbacks observed to date. The XLRP program recently entered P1 and it will be interesting to see whether AGTC will also see the efficacy signals observed by Nighstar.

REGENXBIO (RGNX) reported an update from its AMD program, which is intended to replace chronic administration of anti-VEGF drugs. Although the company reported a dose-dependent expression of the protein in the eye, clinical outcomes were not as unequivocal with 3/6 patients requiring anti-VEGF rescue treatments.

MeiraGTx (MGNX) continued to enroll patients in three retinal programs (RPE65, Achromatopsia, XLRP), with data expected in 2019.

CNS

Investors should expect a lot of readouts for CNS gene therapy programs in 2019. Similar to the case in ophthalmic programs, the field has one major success story (Avexis) that spurred a lot of activity but so far no home run data have been reported. Companies are focusing on rare genetic diseases such as MPS and Batten (CLN) with a strong preference for AAV9 given its ability to penetrate the brain and efficiently transduce neurons.

Abeona (ABEO) is one of the leaders with 2 programs in the clinic (MPSIII A and B, respectively), with two additional programs (CLN1, CLN3) expected to start P1 by mid-2019. In 2018, the company reported encouraging biomarker and imaging data for its MPS programs but so far could not demonstrate unequivocal neurocognitive effects. With no new data since May 2018, 2019 is going to be an important year for both programs. The MPSIIIA program will focus on younger patients hoping to see neurocognitive stabilization or improvement in 6-8 patients, which may be sufficient for approval.

Amicus (FOLD) recently became a dominant CNS GTx player via the acquisition of Celenex in September 2018. The company now has two clinical stage programs for Batten disease (CLN6 and CLN3) and multiple preclinical programs (CLN8, Niemann-Pick C). In its R&D day, Amicus presented encouraging anecdotal results for the first two patients, indicating disease stabilization.

FOLD

REGENXBIO (RGNX) expects to have three CNS programs in the clinic by YE2019. RGX111 (MPSI) and RGX121 (MPSII) are actively recruiting patients with preliminary data expected in 2019. A third program for CLN2 is expected to enter the clinic in 2019.

Beyond rare diseases, there are multiple gene therapies for Parkinson’s disease, most of which are designed to increase dopamine levels in the brain and do not address the underlying cause of the disease. Voyager (VYGR), Axovant (AXON) and MeiraGTx (MGTX) have programs in the clinic.

Ex vivo gene therapy

In 2018 three ex-vivo gene therapy companies got listed. Rocket (RCKT), AVROBIO (AVRO) and Orchard Therapeutics (ORTX) joined Bluebird Bio (BLUE), which is still the leader in the space. The companies are using lentiviruses to transduce blood cell progenitors outside the body (ex vivo).

Bluebird, which became more of a CAR story following promising BCMA data in multiple myeloma, continued to advance LentiGlobin for Beta thalassemia and Sickle cell disease (SCD). Recent data at ASH demonstrated good efficacy with an optimized manufacturing process in SCD but a case of MDS in one patient raised concerns among investors despite the fact that the cancer cells did not contain LentiGlobin’s transgene. The company guides for a potential approval of LentiGlobin in 2019 in Beta thalassemia, initially in Europe.

Rocket presented data in Fanconi anemia which demonstrated some signs of efficacy but totality of clinical data were inconclusive. The company expects to start dosing patients with an optimized process in 2019. The company expects to advance three additional programs to the clinic, including one in vivo AAV-based program for Danon disease.

AVROBIO started 2018 with promising data for its Fabry program but a recent update was disappointing due to lack of persistence (see my take here). In 2019, the company will provide updated results in Fabry, including data from an improved manufacturing process that could improve persistence and expects to start P1 for two additional programs (Gaucher and cystinosis).

Orchard has already an EU approved product for ADA-SCID (a rare immunodeficiency syndrome), originally developed at GSK. The company has four other clinical stage programs including two immunodeficiency programs, one rare metabolic program and a program in Beta Thalassemia.

siRNA

Another important 2018 landmark was the first approval for a siRNA drug, Alnylam’s (ALNY) Onpattro for TTR amyloidosis. The road was admittedly longer and more expensive than originally anticipated (17 years from the first paper to describe siRNA in human cells, 16 years from the establishment of Alnylam and 14 years from its IPO), but at the end of the day it should be viewed as a major success story with a validated class that should generate a steady flow of new drugs going forward. The next step for the field would be validation of siRNA drugs using  GalNAc delivery which carries a major overhang following revusiran’s P3 termination due to mortality imbalance.

At a market cap of $9B Alnylam is not a steal yet I would feel much comfortable owning it today vs. owning Moderna at $5.6B. mRNA drugs have an explosive potential and do not directly compete with siRNA drugs but if history is of any indication, mRNA could be years from realizing its potential. Alnylam has everything Moderna lacks: Clinical validation across multiple agents, genes and indications (so far limited to liver diseases); a clear translational route from in vitro through animals to humans and market assumptions that stand up to scrutiny.

Portfolio updates

I am selling Endocyte (ECYT) and Sunesis (SNSS), adding another position in Stemline (STML) and starting a new position in Chiasma (CHMA).

Portfolio holdings – Jan 13, 2019

Biotech portfolio - Jan 13, 2019

BIOTECH ETFS - 13-1-2019

247 thoughts on “Investment ideas for 2019

  1. Hi ohad , Thank you for this excellent summary. Very interesting stuff and thoughts as always. Can you explain your investment case in CHMA ? And do you think STML has a reasonable Chance of being acquired in near Future? Thank you and have a nice WE.

  2. Carlos – Thanks. CHMA should report P3 data this year and I think they have a reasonable chance of meeting 1ry endpoint based on their previous P3 (which didn’t have a control arm).
    STML – There is still uncertainty around # of eligible patients so I think a potential acquirer would want to see 2-3 Qs post launch.

    Alex (CHMA) – Good catch, it’s a glitch on Yahoo Finance I couldn’t solve, in any case I factored that in by reducing the amount I earned on paper in the cash position.

    Ohad

  3. i must have missed it when you removed BLUE bluebird
    from your portfolio. what could have been the reason?

    thanks again

  4. CHMA look a compelling story but it will be a change to buy shares. The volume on Fri was 2.1k shares!?! If a couple of us decided to buy on Monday, the stock would easily double.
    Thanks for the excellent bio-market overview. A lot of names to add to the “watch” list.

  5. Ohad,

    Lots of stock plunged due to market correction. What do you think on UMRX? thinking create a list with great potential and reasonable price.

  6. “Richard Baker (ADVM) – Their cash position is a big advantage but recent setbacks took away most of the upside potential imo. Not optimistic about their AMD program. ”

    Ohad, why are not optimistic about the AMD program? What’s left, if not the AMD program? Will the stock remain in your model portfolio?

  7. RM (BLUE) – I don’t recall adding it. I’ve always followed it closely but don’t think I ever owned it (unless I am missing something…). I don’t have anything against owning it, waiting for a better entry point.

    teddy (ARCT) – Don’t know them well, need to take a closer look.

    andre (CHMA) – Yes, thin trading.

    Kenny (UMRX) – Definitely a name to follow as they offer a different angle to CAR but differentiating it clinically is going to be a challenge unless they pick new targets or show activity in solid tumors.

    Richard Baker (ADVM) – Hope I am wrong but I think it will be very challenging to get significant protein expression with intravitreal administration. Still thinking about whether to keep the stock or not. It’s a long shot but but EV is very low.

    Richard Baker (CRNX) – Agree, definitely worth tracking, no data in patients yet but PD markers in healthy volunteers were positive. The fact they have an oral small molecule with good selectivity is an advantage but on the other hand it’s hard to predict long term safety with a novel small molecule, CHMA uses a validated somatostatin analog so challenge is absorption and local concentrations in the gut.

    Bobjam (PRQR) – Don’t have a strong opinion on them. Signal is clearly there but recent safety issues are disconcerting.

    Ohad

  8. Thanks for the quick response.
    I made a lot of money on EZCH.
    Have substantial private placement stock on ASSOCS.
    A little CGEN and watching it.
    All Israeli companies.
    Too bad you can’t comment on them.
    😉

  9. 6.6 million stemline offering…about 25% dillution and shares now trading around $8.70. wondering why the offering is now when shares are near 52 week lows. Not sure if this is buying opportunity or one should just be cautious and take a wait and see approach?

  10. Hi Ohad,
    Unfortunate timing on the STML add… hopefully their PO pricing will be the baseline and with good results we will see it 2x to 3x over the next couple of years. What is the general investor expectation on ROI for Public Offerings? 2x to 3x in 2 to 3 years? Just wondering – with VKTX and XENE pricing being $18.50 and $14.50 respy and their current share prices at $8 and $7 why are PO investors not lapping them up?

  11. CHMA – Started to dig a bit on CHMA. My big question is on the prior P3 data that resulted in the CRL on their drug in 2015. It looks like for the initial P3 trial that 89% of patients were responding to the injectable somatostatin analogs at baseline. At the end of the P3 trial, 62% of patients achieved disease control with the CHMA oral pill. So, does this possibly suggest that the CHMA oral pill is not as efficacious as the injectable analogs or am I misreading the data? I realize the P3 that reads out 3Q is versus placebo so perhaps not as important for that binary event but perhaps more important for the next P3 trial that reads out in 2020 that is head-to-head with the injectable analogs.

    I do get that even if efficacy is less for the pill versus the injectables there are still the other advantages of having a pill. But, may be important to consider versus CRNX down the line. I listened to the CRNX JPM presentation and it wasn’t clear to me that they expect their drug’s efficacy to be any better than the current injectables. I guess CRNX trades at such a vast premium to CHMA because their drug is a novel drug they designed themself versus CHMA drug being a reformulation of the existing injectables.

  12. Alex (CHMA) – Q3/19 from what I understand o

    Sam (STML) – Obviously not idea timing but they need the money for the launch. They probably waited for approval, expecting a positive impact on share price but I understand their decision.

    Les – There are no rules, hard to say…

    mcbio316 (CHMA/CRNX) – Agree with your assessment, even if CHMA’s SSA is not as efficacious as injectables in some patients, I think many will prefer it as a 1st line option and use the injectables in Tx failures. I am not against CRNX, it’s a matter of risk/reward profile and time to data that sways to go with CHMA for now.

    Ohad

  13. CHMA/CRNX – Thanks for the comments. One other point on CRNX that gets to your point on unknowns on safety: at JPM they implied that their 2nd drug being developed specifically for NET is a bit better than the lead for acromegaly (both are oral sst2 agonists) because it is more potent and they also alluded to potential safety concerns for the lead drug that the 2nd drug doesn’t have. They didn’t specify what these safety questions were but noted that the P1 for the lead drug was clean and appeared to address their concerns but presumably points to potential concerns for longer-term, later stage trials for the drug.

  14. Ohad

    You mentioned INSM as a low EV company with derisked assets. Market cap has doubled in less than a month. Is this too much too fast or is the stock compelling to you at these levels? Also, Arikayce, their approved therapy for the treatment of MAC(lung disease) appears to have gotten off to a decent ramp. Is it this asset or their pipeline that most interests you?

  15. Ohad
    Do you follow ALNA?
    It looks they at the same stage as CHMA – Ph3 top line data In H2. Potentially filling for BLA thereafter (6mo follow up of 400pt.).

  16. What is your view on the IMMU CRL? Cited CMC issues. It doesn’t seem to be related to clinical data and no other study is required. You liked the data so could this be the right time to step in once we have further guidance from management?

  17. Hello Ohad,

    isn’t TBIO very undervalued when you compare to MRNA? They have a Phase II product!

    Thanks
    Toby

  18. Hammer time…I was looking at $MGTA and really fascinated by what they are doing…through my research I came across $STRO Sutro Biopharma…any thoughts on them? Thanx sir

  19. I see it is debated about Nordic Nanovector, and they may have great news to report in 2019.

    25. okt. 2018. Nordic Nanovector’s Betalutin receives promising innovative medicine (PIM) Designation in the UK for the treatment of Follicular Lymphoma

    Nordic Nanovector’s Chief Operating Officer, said 02 january 2019.
    As we advance with Betalutin® through the pivotal PARADIGME study we are putting in place key elements for its commercialisation pending approval.

    nordicnanovector.com

  20. EDIT/CRSP/NTLA – Ohad, with news of EDIT CEO stepping down, that leaves 3 high-level EDIT execs that left within the span of a year (CFO and CMO left earlier). Have to wonder if this is an overall bearish sign for CRISPR or just specific to EDIT and thus a bullish sign for CRSP and possibly NTLA. Or it could all just be noise though I find 3 high-level exec departures unlikely to just be random noise.

  21. Ohad
    Any opinion about BHVN?
    NDA in ALS. 3 platforms, 3 drugs by 2021.
    Looks low risk – all programs clinically validated. Not sure about valuation – 1.6B.

  22. Ohad, what changed your mind about ADVM’s wet AMD drug? The primate data looked awfully strong.

  23. mcbio316 (CHMA/CRNX) – Yes, with small molecules long term safety is always a wild card, especially in non-oncology indications.

    Les (LPCN) – Impossible to interpret this small non-controlled study imo…

    Dave (INSM) – I am mostly interested in Arikayce, good pricing and a strong launch. Waiting foe a better entry point.

    andre (ALNA) – Yes, vert interesting approach that makes a lot of sense, I just find their clinical validation too soft to support P3. Market cap is low for a P3 company ,though.

    Kenny (NTGN) – I am still on the sidelines as I don’t believe in cancer vaccines approach even with NeoAgs. I like their T cell expansion program but it isn’t in the clinic (expect to start P1 this year).

    Nick (IMMU) – In principle yes, but I would wait for more clarity from management because timelines are still opaque, especially in light of the shut down.

    Toby (TBIO) – Everything is undervalued when compared to MRNA….
    Don’t know the mRNA field well to form a concrete opinion on TBIO, approach is def interesting.

    Robert goulet (STRO) – Their pipeline is too early IMO, they should have a lot ADC technologies but couldn’t find a lot of info on the CD74 and FRa programs. The animation in their IR section is addictive, though…

    mcbio316 (EDIT/CRSP/NTLA ) – Don’t know what to think, it doesn’t look coincidental but EDIT conveyed that everything is on track development-wise.

    andre (BHVN) – Sorry, don’t know them well.

    Richard Baker (ADVM) – I am just cautious after failures with other programs in AMD or with intravitreal administration.

    Stevengatxje (CHMA) – Hard to say, depending on the data but if it’sa home run upside is very significant.

    Ohad

  24. Ohad
    SEEL just started trading.
    They have 2 drugs in PTSD/MDD and Parkinson. They expect to start 2 pivotal Ph3 trials in 2019 in US and EU.
    Due to the reverse merger the valuation is extremely low – 26M with 18M cash.
    What do you think about their programs.
    VKTX started in the same way with licences from LGND and now is 560M company. Actually the CEO of VKTX is in the BOD of SEEL.

  25. Ohad, do you have an opinion on VRCA? Looks like great Phase III results in an underserved market.

  26. Thanks for your comments on IMMU. Looks like it rebounded from when I posted already.

    I wanted to get your thoughts on KPTI. I know you and I have discussed before, but it seems really attractive at these levels with a market cap of 546MM. We have a few near term catalysts as well, including the ODAC (ad comm) in late Feb and eventual PDUFA on April 6. Additionally we will be seeing early safety data from the other two compounds, eltanexor, and KPT9274. Any PD signals could provide further upside. I’m curious to hear what you think. Thanks as always.

  27. Ohad,

    you will hold through the P3 results of NERV, correct?

    How risky do you see their P3 in general?

    thanks!
    Christian

  28. hi Ohad,
    OVID down enough for a buy or not so interesting anymore for you?
    thanks and have a great time
    Paul

  29. Ohad
    Do you like the VYGR deal?
    It might bring back confidence in their Parkinson’s program.
    They will have 350M cash and 50% reduced expences in both programs PD and FA.

  30. Ohad/Nick

    I invested in KPTI when they dropped a few days ago, as I am optimistic about their upcoming FDA meeting. Would love to get Ohad’s thoughts. Some of the issues that convinced me:

    —There are very few drugs in oncology that have a 26% ORR in patients who have failed 5 different drugs.
    —8% grade III nausea is a concern (especially in an oral drug taken every day), but is probably surmountable with better prophylaxis. On the other hand, no neuropathy which is usually treatment-limiting in extensively treated patients. Also, in combination studies, less neuropathy is seen.
    —Not randomized, but the fact that nonresponders have an OS of 1.7 months versus 15 months for >=MR suggests that there are no other good alternatives for this group of pts and the improvement in responders is meaningful.
    —since accelerated approval depends on lack of other options and serious unmet need hopefully will get marketed in 2019 while awaiting phase III combination data

    Thanks as always to Ohad and other blog members. I really find the dialogue invaluable.

  31. Do you have an opinion on LPTX? Seems to have a lot going on for a $34 million company. But really short on cash.

  32. ESPR

    Ohad,
    how do you see the europe deal? is there still a reasonable chance for a buyout after this “deal terms”? where do you see the stock price after potential approval next year?

    Thank you.

  33. RGNX

    ohad, do you still like the stock and keep on adding at these levels? how much of the valuation is covered by royalties/milestones from NVS / BOLD? EV seems quite low with about 470m in cash at the end of 2018. Maybe you could give a short update about the stock. Thanks :-)

  34. Ohad,
    Thank you for the very informative update. I really enjoy reading your posts.
    Any opinion on Y-mAbs Therapeutics? They are currently conducting two pivotal phase II studies in different neuroblastomas.

    Thanks.

  35. Why no mention of NASH stocks in your post? One of the current hottest areas with lots of momentum too…

  36. TRVN doubled last week .62 to 1.40 and then dipped back to 1.0 on a private offering on Thur/Fri. Now back up to 1.32 over Mon/Tue. Anyone holding TRVN have comments?

    Hi Ohad – will appreciate your comments on TRVN recent updates- I know you got it out of your portfolio mid last year after the lack of positive results but will really appreciate your thoughts.

  37. Declan (CAPR) – Didn’t delve deep but at first glance didn’t find it compelling.

    andre (SEEL) – Wasn’t aware of them, will take a look.

    . on January 26, 2019 at 9:59 am said: Edit
    Ohad
    SEEL just started trading.
    They have 2 drugs in PTSD/MDD and Parkinson. They expect to start 2 pivotal Ph3 trials in 2019 in US and EU.

    Andrew c (LPTX) – Sorry, haven’t been following this program.

    Richard Baker (VRCA) – Sorry, dermatology is out of my scope.

    Declan (AUPH) – Hard to say… 1ry endpoint eventually wasn’t met so I would take everything with a grain of salt.

    Nick (KPTI) – I am still struggling with this one… the myeloma data in penta-refractory patients are positive but market is very competitive, they have some other efficacy signals but no home run data set yet plus safety is still an overhang. Anxious to see data with their next gen compounds to see if decreasing brain penetrability resolves some of the tox. Bottom line, still on the sidelines.

    Christian (NERV) – Correct. I think risk/reward is ok, especially for a CNS program.

    Larry Holt – It’s always hard to predict how broad the effect will be. I personally don’t think there is so much rising on CRISPR today as the exposure in the biotech field is still limited (similar to siRNA 7 years ago).

    Les (TRVN) – Sorry, not following them anymore.

    paul (OVID) – I decided to wait as clinical data in Angelman were disappointing. CH24H program is interesting but still early.

    andre (VYGR) – In the short run the deal reduces cash burn and provides non-dilutive funding but I view it as a sign of weakness and long term economics aren’t that compelling IMO. Same for the MGTX deal, they are giving a lot of upside for a limited upfront payment.

    Josef (VYGR) – Agree about EV. Upside potential is more limited now but the risk of dilution is significantly reduced. I still like their early stage programs.

    Carola (MGTX) – Still prefer to wait for data, especially now that the RPGR program is partnered.

    Gary (KPTI) – It’s one of those cases where a drug has a decent likelihood of approval but I am not sure about initial market performance in a crowded market like myeloma with all the BCMA programs.

    druz –
    FTSV – I don’t like risk/reward given all the issues with other CD47 programs, they may have a differentiated product but still efficacy isn’t stellar so far imo.

    MNOV – Sorry, don’t know them well.

    Richard Baker (LPTX) – Sorry, not following them.

    James (MGTX) – Yes, but economics are somewhat underwhelming and upside potential is capped significantly now. Still like the xerostomia program.

    karlos (ESPR) – Hate to sound negative on all the deals today but I also found this one disappointing, near term it removes a lot of financial concerns, don’t think anybody will buy them before they get approval.

    svenja (RGNX) – Yes I still like it given the vast exposure to many AAV 8/9 programs. I am still a little concerned about te lack of a clear wholly owned value driver but this may change with their MPS programs.

    Lasse (YMAB) – Don’t know them well. GD2 has been a round for years so not sure how different their naked mAb is, the radioconjugate is a high risk program because it is an IgG.

    Kay Lee – You’re right, other than MDGL and VKTX I am not very familiar with the field. Not very optimistic on ICPT’s readout this year, though…

    Les (TRVN) – Sorry don’t have a strong opinion here….

    Richard Baker (APTX) – Not sure, NMDA modulators (positive or negative) are very interesting with so much potential but very hard for me to evaluate them.

    Ohad

  38. Ohad
    ABEO has 300M market cap and >100M cash.
    It looks the market does not believe in their programs.
    Do you agree with the market?

  39. Ohad, always nice to see you continue to be objective, even if negative.

    Where do you stand with XENE and CHMA. Are those still good risk-reward buys?

  40. Gene therapy

    Are you still positive on Gene therapy in General After the recent set backs? Of do you think about eliminating some stocks from your Portfolio? There was a huge sell off for rgnx Abeo nite advm agtc etc…

  41. Ohad
    do you follow CNST?
    Two Ph 2 updates this year. Indicated that they will start in 2019 talks for pivotal trail(s) with FDA after the data !?!
    240M cap with 120M cash. Cash until Q2 2020.

  42. Ohad – Kodiak Sciences (KOD) is developing a long lasting 12-20 wk duration anti-VEGF (KSI-301) for wet AMD + DME and RVO. They will enroll a 400 pts in a phase 2B pivotal study in 2Q 2019, with interim and primary readouts in 2020 and 2021. Have you looked at them?

  43. Hey Ohad,

    Any opinions on GILD NASH failure and any implication for MDGL VKTX- maybe a catalysts for shares to start climbing up.

    Thanks,

    Dan

  44. Synthorx (THOR) non-alpha IL-2 looks interesting as well. Pre-clinical data looks intriguing. All comers solid tumors P1/2 IND filing in 2Q and poc data 4Q 2019.

  45. Hey Ohad,
    Any opinions on the esketamine SAC? And how the vote may affect approval chances of other drugs for MDD – VTGN RLMD AXSM SAGE
    Thanks!
    Dan

  46. Hey Ohad,

    What are the implications of the esketamine SAC vote for other stings for MDD, if any? AXSM VTGN SAGE RLMD.
    Thanks!
    Dan

  47. Ohad
    Good new for JnJ for their exketamine spray.-14:2 panel vote.
    SEEL has pivotal trail ready drug – racemic ketamine nasal spray for similar indications – suicidality, PTSD and MDD.
    JnJ panel vote looks to validate the SEEL drug.
    The second program is partial dopamine agonist for Parkinson’s Disease with positive ph 2, but shelfed by LGND after an acquisition of a company.
    I would appreciate if if you look into this company. Unique case – 25M cap is very low, considering the both programs are sort of validated.

  48. Hey Andre,
    Re SEEL: is the market cap $25 million? Strangely I have seen different valuations on my brokerage. Not sure why.
    Dan

  49. Hi Ohad,

    Thanks much for your valuable comments.Appreciate them a lot.

    Any comments on FCSC? Big jump today after the Feb11-12 CEO webcast indicating positive progress and possible Ph2 readout very soon. Stock jumped 10% today and likely big jump coming soon. Patient population seems very small though for their drug – 2500 in US. Does the value lie in their approach and potential use in other applications?

    Also BIS seems to have taken a beating – dropping from 26 to 17. seems to be value in it only if you take profits like any other stock – not hold for the long term like a biotech.

  50. ABEO

    Can you Write a few words about the actual Development at Abeona and the reason why the Stock is hated by the market these days. Also has KRYS a higher chance of success with their program? I See you Go with Both stocks. Thanks!

  51. Hi Dan
    My understanding from the merger agreement is that the outstanding shares are 6.22M. APRI got 15% or ~1M shares.At $4 it makes $4M for APRI stockholders, which was the EV of the company before the merger. Just based on the APRI deal I think $25M is correct
    There are some similarities between SEEL and VKTX – drugs from LGND with validates MOA. Let’s see if SEEL can do the VKTX trick. Starting one of the pivotal trails could be the trigger.
    I got 2k shares starter position. Waiting for Ohad opinion and for the inenevitabl secondary before buying more shares, if at all.

  52. Andre, Dan, SEEL has dipped more than 10% since your first post. You folks have taken a ‘Ohad like’ position already 😊. Seems you have a high degree of confidence based on LGND pedigree (although LGND itself has taken a beating). Data so far looks that good?

  53. ALSO – do you have any comments on TRVN and FCSC?

    Keeping fingers crossed on ICPT. Things don’t look so good. Recent piece on SeekingAlpha seems to think GILD will acquire GALT or MDGL on failure of their NASH drug. VKTX being couple of years behind. Any ideas on that front?

  54. Hi Les
    Sometimes reverse mergers offer nice opportunity.
    Check Ohad blog from Sep 2017. I asked about ITEK / RCKT reverse merger. I took a starter a bit too early, got some beating of ~ -15% when the stock dropped below 4.
    Ohad was positive about the technology, so I doubled down.
    Exactly one year later RCKT was trading at $25. Sold my initial 2K shares, still holding the rest and still like the company.
    The history may not repeat with SEEL, but the current cap of 23M is compalling, so I decided to gamble a bit until the secondary.
    At that point I will see what to do – sell, buy or nothing

  55. Thanks Andre. Bought some too. For all the NASH watchers – I was apprehensive about ICPT but it turned out well. Glad I held some shares through the results. Unfortunately VKTX got hit short term by the news.

  56. HI Ohad,

    Based on the low valuation, I too would love if you looked into SEEL. Any thoughts about the Parkinsons data from NTEC this morning? Thanks so much, appreciate all your feedback!

  57. Andre & SEEL followers,
    SEEL dropped some more… not sure why but may be this – Just saw a news release that ORPN (Pontifax) sold its Trehalose assets to SEEL for development. ORPN is up big but SEEL dropped. Maybe secondary offer as you said may be needed for the development. Why would SEEL acquire this if they just had a merger?

    Ohad – would really appreciate your opinion on SEEL.

  58. Hello Ohad,
    I too was piqued with the SEEL commentary- until now, when I came across the “Citron Publishes the Smoking Gun on Ligand Pharmaceuticals” article, where they published pictures of the purported SEEL offices in NYC. I would suggest that anyone interested… google that and decide what to make of SEEL.
    I also was aware that Viking VKTX took a hit a few weeks back when this article first surfaced, also because of their formative ties to Ligand. Unfortunate because VKTX is an important position for me.
    I would much appreciate it if you could comment on the Citron publication. Is VKTX still a worthy investment? Thanks,
    Lawrence

  59. Any SMID cap companies come to mind that you think has the potential to the next Celgene, Gilead, etc (large caps)? BLUE, AGIO, BPMC, SAGE come to mind based on the potential of those initial platforms. Maybe RGNX, ONCE, BOLD if current generation gene therapies take off.

  60. Hi Ohad,

    Appreciate the great blogging! Ive been looking into the epidermolysis bullosa drug developers. Do you have any preference between ABEO, KRYS, and, FCSC? I took a small position in KRYS, if they can continue to show positive data with a topical allogeneic gene therapy, I think it has very interesting upside.

  61. Do you think autologous CAR-Ts will ever have a successful commercial product? How do you see BLUE’s bb2121 doing commercially vs other BCMA approaches (BITEs, bispecifics, allogenic)? In the allogenic space do you have any opinion on ATRA? thx

  62. Hi Les and other
    Sorry if I misled you with the SEEL story
    The deal today does not make sense, so it’s a red flag.
    Reading some financial disclosure docs I realized that behind the 18M financing there are a lot of warants, another red flag.
    I did a sloppy DD here.

  63. andre (ABEO) – I thought recent updates from MPS were disappointing as the clinical signal wasn’t as strong as biomarker data, could be related to age and stage of disease but still. I plan on holding them as valuation isn’t high and they have multiple shots on goal.

    Bio Executive (XENE/CHMA) – I like both as cheap , high probability of success stories (with all the obvious caveats…). Plan on holding both.

    Sereb (Gene therapy) – Yes I am still positive but have to admit the degree of failures and setbacks surprised me. This is beyond normal attrition but I hope that at least some of the names you mentioned will have good data this year.

    andre (CNST) – Haven’t looked at them for a while but overall no very optimistic about EZH2 as a target.

    biocqr (KOD) – I think it’s a high risk program and validation in the clinic is limited, NVS new VEGF product will raise the bar even higher. Don’t see a reason to own it now.

    Dan (GILD) – Don’t think it has any implications besides removal of potential competition. Ask1 inhibitors have never demonstrated a robust clinical signal in contrast to Thrb agonists from MDGL and VKTX.

    biocqr (THOR) – personally I don’t share the excitement around IL2 variants, so far monotherapy data was disappointing and NKTR’s single arm data are iffy. Reminds me of the IDO craze 2 years ago. I don’t think risk/reward is favorable with the current valuation.

    Dan (esketamine ) – I think people are going to use it but there is a lot of room for new agents with improved (safety, oral) clinical profile.

    Toby (GRTS) – I think the right way to pursue neoAgs is via cell therapies, not cancer vaccines, so I prefer to wait until such programs from GRTS and NTGN mature.

    andre (SEEL) – Sorry, not familiar with the story here.

    Les (FCSC) – I prefer other approaches from ABEO and KRYS. Don’t think market size is the problem as pricing will be probably high.

    BIS – As an ultra short ETF, there is obviously a lot of volatility but I plan on keeping my position as a hedge.

    Carlos (ABEO) – Ithink the primary reason for weakness is disappointing MPS results, so far the strong biomarker reduction even in the CSF did not translate to an unequivocal clinical benefit. Yes, for DEB I prefer to go with both names, both programs are high risk IMO but rationale is strong.

    Lawrence (MEIP) – Not following them closely but not excited with HDAC inhibtors, similarly to other epigenetic drugs that appear to broad.

    Les (TRVN/FCSC) – Not following them closely.
    ICPT – I was positively surprised by the data but profile is still unfavorable IMO. Good for next gen FXR agonists which are hopefully safer and more potent.

    Kenny (EOLS) – Sorry, don’t know the field well.

    Chad (SEEL/NTEC) – Sorry, still didn’t have a chance to take a closer look, too much work…

    David – That’s a tough question… It also makes you wonder about teh importance of a productive platform vs. one big success story that can be leveraged to expand the pipeline. Both GILD and CELG belong to the latter type imo.

    David (ABEO/KRYS/FCSC) – Thanks. I decided to go with ABEO and KRYS. Agree that the profile offered by KRYS is an ideal one that does not involve cumbersome production.

    William – I sure hope they will. I like BLUE’s bb2121, there is so much going on around the target so hard to predict…

    Ohad

  64. Any comments on Guardant Health (GH) that claims to use big data, machine learning and genomic sequencing to diagnose cancer through blood testing rather than tumor biopsies?

  65. Andre, backed out halfway out of SEEL and switched to GALT and VSTM. Hope to make up losses there. CBAY is also moving up. NASH is getting really crowded.

  66. Negative news for KPTI, FDA on KPTI “limited efficacy and significant toxicity demonstrated in trial population, it is unclear whether treatment with Selinexor-dexamethasone provides a clinically meaningful benefit that outweighs the risk of treatment”

  67. I thought the data looked better than the FDA interpretation, but they are considering all infectious deaths on study due to drug regardless of time off therapy. Given the patient population and their general medical condition, that is unlikely, but I see their point in a non-randomized setting. It does look like they will require the phase III BOSTON study with top-line results in Q4 19 for approval…..

  68. ONCE to be acquired for 5B?
    I bit strange that it’s not PFE or NVS, ONCE current partners, but Roche?

    Ohad, if true, what program you think was driving the deal?
    Hem A (un-partnered) but not impressive
    Hem B -partnered with PFE and inferior to QURE
    Choroideremia – behind NITE
    Pompe – too early
    CNS – also pre-clinical
    Luxturna – NVS partner, not impressive sales projection – 64M/year

    Very happy, just trying to learn a bit and project to my other GT stocks.
    Buying more NITE and QURE as next potential target?

  69. Unbelievable… Ohad do you sell your magic crystal ball? 😛
    again showing your Biotech skills… thank you for this fantastic investment
    Paul

  70. ONCE

    Does the buyout raise the value of other GT companies like RGNX ABEO NITE BOLD … in general?

    Thanks for your opinion

  71. This Guardant Health GH has me skeptical after the theranos failure. Do you think it is possible to do cancer detection using 2 drops of blood?

  72. Howard (GH) – Sorry, not following the field. Sounds like there is a lot of progress but don’t have other observations there.

    Liang (VSTM) – I am not sure they have a differentiated drug in a highly competitive marketplace.

    DJ/Gary (KPTI) – Yes, ODAC was quite harsh on them. The most cocerning part was the lack of efficacy as monotherapy, leading FDA to speculate what they are seeing is within historical efficacy of dexamethasone (which I find hard to buy). Puts emphasis on their next gen XPO1 inhibitor with lower CNS penetration but still waiting for human poc.

    Les (VYGR) – They are doing great job on the BD front while keeping the relevant early stage programs in house. I am still concerned about their data in PD but like their pipeline.

    andre (ONCE) – Agree it’s surprising. I guess that just like NVS Roche decided they want all in on GTx. Hard to say what was the primary driver, probably HemA after all, the regulatory experience and production capabilities are clearly very important as well. Pompe is also very interesting IMO.

    paul – Thanks! Could use a magic crystal ball now and then in this business…

    Carlos (RGNX ABEO NITE BOLD) – Yes I think it does because it solidifies GTx as a mainstream modality among pharma companies. Today it is hard to find large pharmas without GTx exposure which is a good endorsement long term. Needles to say, this cannot replace clinical data.

    Ohad

  73. Any thoughts on Genmab?
    New SC data for Darzalex and some promising candidates in pipeline (HuMax-TF-ADC/Tisotumab vedotin and HuMax-AXL-ADC/Enapotamab vedotin)

    -Lasse

  74. $eidx Eidos Therapeutics JP $EIDX AG10 has the potential to be a best-in-class stabilizer in the evolving TTR amyloidosis (ATTR) space. We will get news of phase 3 trial design on Wed. However, $PFE tafamidis has a PDUFA target date in July 2019. Do you believe that that risk/reward is attractive despite later to market and having a large pharma as a competitor?

  75. Kodiak (KOD)…
    > NVS new VEGF product will raise the bar even higher. <
    brolucizumab is 12 wk dosing…KSI-301 is shooting for 20 wk dosing. Baker Bros own 24% FWIW. KOD claims superior PKs so we'll see.

  76. Hey Ohad,
    I know you let the data guide your investment decisions, and generally wait for results to mature, but There are times you also have taken shots before any results – SNSS is such an example; I think you were attracted by the target and class of drugs.

    So here is my question: why not APTO – they are about to initiate two ph1 trials for their pan BTK / pan FLT3 molecule. Market cap is very low at $70M and this looks like a unique molecule which may recruit patients very quickly. Why SNSS (6months ago) and not APTO? Additionally their myc inhibitor is already recruiting on Ph1.
    Thanks
    Dan

  77. Positive news today on $eidx. Do you share JPM’s positive view that ” the company’s design of the ATTRibute-CM study, which incorporates feedback from the FDA, removes multiple overhangs, including the need for a head-to-head study versus tafamidis and a financing overhang. The analyst, who has increased his view of the probability of success for AG10 in the ATTR-CM opportunity, also believes AG10 is likely to generate strategic interest fro
    m commercial partners. It’s up about 15% since my previous post. How do you feel about valuation, risk/reward… possible future addition to your portfolio?

  78. Hey Ohad,

    regarding CHMA I wonder what gives you some confidence about the two ph3? Is there anything they are doing differently than last time, 2 years ago, when the FDA rejected their drug? What gives you confidence this time around that it will end up differently?

    Thanks
    Dan

  79. Dan

    I have been following APTO for several years and am baffled by the stock action for the last year. They seem to move at a snails pace and they spend very little money. Dr. Brian Drucker who is synonymous with gleevac, presented as a KOL in December for APTO and said regarding there CG-806 molecule a potent pan FLT/BTK inhibitor :
    “CG-806 is unlike any molecule we have investigated, and it is more than just a FLT3 and BTK inhibitor,” said Dr. Druker. “806 has the unusual ability to suppress key driver and rescue pathways and overcome the resistance that develops with other kinase inhibitors, and it has demonstrated potent activity against actual primary cells from patients with hematologic malignancies. We are hopeful that clinical testing will prove it to be a new treatment for a patient population in need of new options.”

    Ohad: As Dan stated the mkt cap is sub 100M. What keeps you away from APTO and what did you see in SNSS that caused you to buy?

    Thanks again Ohad

  80. Ohad
    IMGN – does it look attractive at that level – almost at cash. And the pipeline is not zero – 3 Ph 2s combo plus mono may work in high FRa pts. Actually they met the stat-sign in this group but due to some strange design the trail is considered fail.

  81. Hey Ohad,

    Any thoughts about Foward I results?

    http://investor.immunogen.com/news-releases/news-release-details/immunogen-announces-top-line-results-phase-3-forward-i-study

    Despite missing the topline endpoints, in the pre-specified subgroup (n=218) FR-alpha high patients vs chemo we had:

    PFS: HR=0.69 p=0.049
    OS: HR=0.61 p=0.03

    As indicated by Immunogen, the Hochberg procedure they used for required p=0.025 for statistical significance due to the failure to achieve statistical significance in n=366 FR-alpha med+high patients. The OS results for the FR-alpha high group was not a pre-specified endpoint, but I think Immunogen may have sufficient data to apply for approval in this subgroup.

    The FDA may convene an ODAC, but I think it could favor approval given the dearth of available treatments for pt-resistant EOC patients that are both safe and effective. This is more evidence than the single arm PII for an enriched subpopulation that olaparib was approved on.

    Your thoughts?

  82. Ohad,
    Re: DNLI.
    Interesting study recently published on life-long LRRK2 reduction in 1,358 loss-of-function carriers.
    Your comments on DNLI, in past posting, raised safety signal concerns. Does this study result change your assessment?
    How significant a lead does DNLI have in LRRK2?
    Valuation still too high in your estimate?

  83. Hey Ohad,
    Have you looked at MBIO recently and especially the gene therapy licensed out of st Jude’s? It’s in phase 2 for xscid (bubble boy) What might be the value of that program?
    Dan

  84. Hey Ohad hope you had great weekend.
    Have you looked at Tocagen (TOCA)? Looks like a good gene tx company with decent mkt cap and advanced candidates with 1 at ph3 readout this year. Also good management team. Kindly let us know your take on them.
    Thanks DJ

  85. Biogen to buy Nightstar Therapeutics for about $800 mln
    Great job Ohad bringing this to our attention.

  86. NITE

    Congratulations again. Nice Track Record now 😉

    BOLD

    Also here a acquisition makes sense and is high likely imo. Stock did rise a lot these days. Could you please speculate a Price Tag? Do you think there is more upside to current prices?

    Other GT
    Which other GT companies do you Plan to add? Seems that there a not many left which are far in progress with p3s..

    Greetings from Germany
    Karlos

  87. NITE… reaaaally Ohad, again 😀
    congratulations to all, of course especially to Ohad

  88. KURA

    are you still positive on this company? your position seems quite high.

    do you see takeover interest or do we have to wait here?

    Thank You. Sven.

  89. Hey Ohad,
    Good call on NITE, how we the premium is a little disappointing, do you think that the lack of manufacturing facilities could tributes to the low premium; after all NITE was at the same price level Biogen’s is paying on October.
    Thanks
    Dan

  90. With the NITE news, hard not to jump to negative conclusions about AGTC. With Biogen ending their deal with AGTC and then almost immediately inking a buyout at NITE. Seems like perhaps they had enough data from both groups to make that decision. Nevertheless, congrats on yet another spectacular call. You have an incredible vision for these things. I went back to read your blog from 2016 when you first mentioned GTx and you were spot on with your predictions. So impressive.

    Which new fields are you looking at? Microbiome seems to keep coming up on my feeds lately, but I never got into the space so I feel very far behind. Gene editing seems to be immature still. I like the idea of looking into targeted protein degradation but there are very few data that have validated the tech to date.

  91. Ohad,
    With all these recent GT buyouts, what do you see as a fair value for QURE? Are you a believer in QURE thus far? Thanks

  92. Hey Ohad,

    Last week I noticed that GlaxoSmithKline took a 14% stake in GNCA, and NEA owns 49%. The market cap is ~85 million. What do you think about the company/valuation and how would you rank their tech compared to Neon and Gritstone. Thx

  93. Hi Ohad wanted to know your thoughts about Homology Medicines (FIXX) seems like they have both gene therapy and gene editing capabilities.

    wondering how you would rank the players in the Epidermolysis space between krys, fcsc, and abeo.

    Any gene therapies that you would and wouldn’t buy new positions in based on current valuations? Specifically curious about BLUE, RGNX, BOLD, and MGTX

  94. A lot of management turnover at Agios, David Schenkein is now at GV although staying as executive chairman and their CCO just left to be CEO at Deciphera. What do you think about the growth story/investment in AGIO today under Jackie Fouse? Do you think the IDH franchise will be a success? PKR activator Mitapivar, MTAP, DHODH program + the other preclinical programs. Any personal thought about the company are greatly appreciated.

  95. Hey with Clementia being acquired for 1Billion+. Do you think BPMCs drug in FOP could be a value driver that’s under appreciated in their pipeline right now?

  96. Ohad – Please tell me what you think about Unity Biotechnology (UBX), Mustang Bio (MBIO), and Rubius Therapeutics (RUBY)

    Thanks so much

  97. Big pharma behaves like a maniac and buys as much GT companies with progressing programs as they can. Thus RGNX and ABEO and BOLD are the next hot targets. Do you agree?

    Do you Plan to hold AGTC?

    Thanks,
    Thome

  98. Hey Ohad,
    Does the recent M&A activity in GTx change anything with ADVM? Any value in their partnership with RGNR and Editas? And do you think that their only proprietary program of any value is the wAMD Program? If any. And they have scrapped all rate disease programs Ian’s are back at the drawing table.
    Valuation still reasonable considering they have manufacturing facility and significant cash ($200M)
    Thanks for sharing you opinion!
    Dan

  99. Any opinion on Cerecor (CERC) and the also bacteriophage companies CFRX & APHB? Thx

  100. Hi Ohad,
    Congratulations again on NITE – what a prolific run! CBAY has been having quite a run and price targets are running quite high with great optimism about their P3. Do you have any comments? Also XENE has their ER tomorrow – fingers crossed – any predictions anyone?

  101. Hello Ohad ! I would also like to thank you for your Gene Therapy picks !!! I am interested in AVRO! After reading your past comments and noting the huge decline in their market cap, am wondering if they are a worthy addition to your portfolio ???

  102. Hello again Ohad!
    I have a question regarding CANF – they lived drug for cancer and NASH will be reporting this year. Any opinions? Also, results for liver cancer were expected last year but have been pushed back to q1 2019 due to survival. How should we interpret that?
    “Due to Patient Survival, Top Line Results of the Namodenoson Phase II Advanced Liver Cancer Trial Expected Q1/19”
    Thanks
    Dan

  103. Ohad
    you dropped MRNS for a good reason – PPD was not going to compete with SAGE in any meaningful way.
    But they just became a Ph 3 company w/ a trail for children with PCDH19-related epilepsy. They have a long way to go – data in 2021, but Ph 2 data were good.
    Any thoughts about the trail and does it make sense to look into entering MRNS … again

  104. Ohad

    XENE. If I remember correctly you had shown more excitement for XEN1101 and XEN901 than XEN496. With XEN496 in later stage development, do you think a setback will have a material impact on the share price or does the other compounds in the pipeline more than justify the valuation?

  105. I’m curious what you think about Bluebirds MegaTal editing capabilities. Do you think it will be a focal point of their future programs? How does it fare to other types of editing tools such as Talen, ZFN, and CRISPR

  106. Hey Ohad,

    Do you like any company in the CD47 (FTSV, TRIL, SURF) space or allogenic CAR-T? (ATRA,ALLO, CYAD,etc)

  107. Once again……… Congratulations are in order!!! It appears the market likes the progress Arqule is making !!!

  108. Hi Andre,
    SEEL made a big move today. Are you still holding? Any comments? I’m
    holding some of the position I got into following your lead and was wondering whether the news of their Parkinson’s drug licensing is worth an add on position.

    Ohad, will appreciate your thoughts as well. SEEL is a LGND company and acquired ORPN assets.

  109. Hey Ohad
    Rapastinel fails miserably – we have not seen the detail, but how strange; the drug was successful in ph2 and fails ph3- same thing happened a few years ago with AZN lanicimine. Some scientific papers point out that ketamine is a dirty drug that hits different targets and pathways, not just glutamate receptor/ nmda, thus the challenge or replicating it’s effects. For example; there is research showing ketamine positively affects the microbiome / gut microbacteria vs no effect with lanicemine-
    Any opinions on the ph3 failure rapastinel?
    Thanks
    Dan

  110. Hello Ohad,

    Any opinions on sequential parallel comparaison deaign (SPCD)- used to mitigate placebo response in MDD trials- Alkermes used it – first ever use in pivotal studies, and the fda was critical of the design and ultimately rejected their drug. However many CNS companies are now making use of the design – RLMD & VTGN among others, and there are interesting articles that say the fda has to start considering the design- only two drugs ao far have been approved for MDD – and one of them just last week: esketamine.

    Rapastinel probably failed because of high placebo response (typical up to 40% placebo response in MDD trials) – here is an interesting article that discusses SPCD

    http://www.bioworld.com/content/alkermes’-spcd-clinical-magic-right-euthymics

    Dan

  111. Les,
    I didn’t sell my shares but don’t follow them any longer and don’t intend to buy more shares … until they start generating clinical data.
    Just put the stock in the “looser’s basket” along with other gems of mine like AKTX, SNSS and GNCA.

  112. SNSS

    Is there a Low or a high probabillity that they could have a PR too? Results in Q2. Whats your guess? Thanks.

  113. AVRO

    Ohad, do you plan to add at these levels? Valuation seems now reasonable. Thanks.

  114. AVRO

    Ohad, do you plan to add at these levels? Valuation seems now reasonable. Thanks.

  115. Ohad if xerostoma works out for $mgtx I assume where would u put the market cap on this?

    Congrats on Nite…I had a small position in it as of recent…With Nite gone I would have think there is more of a spotlight on $mgtx esp. w/ gene therapy for the eye considered to be low hanging fruit. Also I see $ABEO entering the eye arena…any comment on that (aav24?) perfromed intravitreal ?

    Thanx 🔨

  116. MGTX

    Ohad, How do you See the valuation? Are you optimistic about the Programs?

    Thanks. Babi

  117. Sorry for the slow turnaround, busy days… Will try to reply everything this weekend.

    Lasse Vedel Jørgensen (Genmab) – I think dara is an amazing drug but it’s fully priced in (or close to). So far I haven’t seen another meaningful program that can move the needle for this 10B+ company. ADCs based on SGEN/IMGN’s technology are a tough space as we have all seen… let’s see.

    Sam (EIDX) – While I believe their drug is probably superior to tafamidis I prefer to sit this one out for now as they are just starting P3 and the landscape is changing dramatically. Definitely worth revisiting next year.

    biocqr (KOD) – Agree, we’ll see 😉

    steve (XBI) – I think we will have a broad correction that will include all indices but so far this was proven wrong.

    Dan (APTO) – Don’t know them well but pan BTK / pan FLT3 sounds to broad spectrum (and thus toxic) to me. Myc a super tough target and not sure what they actually have.

    Sam (EIDX) – It’s definitely a positive development for them, the 12 month 6MWD endpoint sounds attarctive given experience with tafamidis and they have a decent shot at meeting this endpoint. Still, they will have to deal with tafamidis one way or another and readout is ~18 months away. Valuation isn’t too high but still prefer to wait.

    Dan (CHMA) – Unlike the previous study, the current P3 is a placebo controlled trial, which should satisfy regulators. Based on previous clinical data, CHMA is able to achieve sufficient exposure and control IGF1 level, whiich is te 1ry endpoint. Nothing is guaranteed, of course but risk/reward looks favorable imo.

    Dave (APTO) – Hope I am wrong but I would go with more selective compounds here.

    andre (IMGN) – That’s a good question…. I don’t see any near term drivers but I am thinking about adding later in the year if valuation continues to drop. Hope they will introduce new technologies or acquire one of the private ADC companies with next-gen ADC technologies. I also thought the signal in FRa-high patients is reliable and should be taken into account in their PD1 combination program.

    Wildbiftek (IMGN) – I am not sure regulators will accept this interpretation, even though the signal looks real to me (without seeing the data) and benefit is significant. The point about their data being more robust than a single arm P2 is a valid one.

    Frank (DNLI) – Yes, my primary issue here is valuation. Otherwise, the biological story looks good. I think they have a significant lead in LRRK2 with two molecules that appear potent with good exposure. Not aware of other LRRK2 programs in the clinic.

    Dan (MBIO) – It’s a tiny market with multiple programs in development.

    DJ (TOCA) – I am bearish on them, data are hard to interpret imo and the approach isn’t compelling to me.

    Xavi (NITE) – Thanks. Not a huge exit but still a good deal for them.

    Karlos (BOLD)- Thanks. Yes BOLD is clearly a good candidate as it has a late stage GTx program that will be first to market with encouraging efficacy (durability is still an open question) + they have other programs and good manufacturing capabilities.
    Agree with respect to other GTx companies , a lot of private ones but not a lot of P3 companies. SRPT is obviously very exciting but I am nervous about durability of dystrophin expression and valuation is quite high.

    paul (NITE) – Thanks.

    sven (KURA) – Cautiously positive as data aren’t as good as I hoped for but may still be clinically meaningful.

    Ohad

  118. IMGN

    FRa high subgroup at 60% of total with HR=0.69 vs overall FRa medium/high HR=0.98, it implied 40% of total FRa medium subgroup HR>1, thus worse than chemo. For FRa medium worse than placebo without really good explanation, it really puts a big question mark on FRa high result because there is something else going on in the study.

  119. Hey Ohad,
    I am reposting this: I wonder if you have any thoughts on sequential parallel comparison design (SPCD) for trials In MDD- it has been used by Alkermes for their depression drug (first time ever for pivotal studies) but FDA was critical of the design. However this design is gaining popularity as a way to mitigate placebo response in MDD trials, which can be up to 40% – So far only two drugs have been approved in MDD (I think, including last week’s approval of esketamine) which shows how difficult it is to show clinical benefits when placebo response can be very high. Any opinion if the FDA will eventually accept this design? Companies like RLMD, VTGN, ACAD and others are using SPCD and there seems an ongoing debate in the biotech press about this.
    Could be that rapastinel failed because of high placebo response?

  120. Dan (NITE) – Yes agree, not a huge exit. Interestingly both NITE and ONCE were bought when they were weak following early clinical data investors were struggling with. I hope updated XLRP data from NITE at higher doses with pre-medication provided the hoped for signal.

    Nick – Thanks.
    AGTC – Yes, definitely doesn’t look good for them given the fact BIIB had rights to their XLRP (RPGR) program and dumped it on the verge of IND filing. Bit I don’t think it’s the final verdict on AGTC, all it takes is one program with an efficacy signal (probably won’t come from their ACHM programs but they have other programs.)

    With respect from emerging areas, I hope that ADCs will make a comeback thanks to new technologies developed by newcomers like ZYME and a host of private companies. Looks like investor and pharma sentiment is at its nadir which might be a good time to explore but that’s highly speculative.
    Don’t know what to think about microbiome, still on sidelines as translation and human relevance are still unclear imo. A lot of provocative data in mice and intriguing correlations in humans but still no poc beyond fecal transplant.

    Gene editing and PROTRACs are super cool but I would be surprised if this would be smooth sailing. If I had to pick one I would go with PROTACs as these are small molecule for oncology with reasonable translational relevance from models. Gene editing is so groundbreaking so I am more concerned about near term applications, hope I am wrong…

    Shane (QURE) – So QURE is one of my biggest “misses” in GTx, proving again that it’s better to go with the basket approach in emerging Tx fields. Their valuation is pretty rich given the limited HepB opportunity but their HD program is very interesting. Still on the sidelines there.

    Jeffrey Broddie (GNCA) – I think their tech is very interesting but their ACT program is still early.

    Brendan (FIXX) – I think they are definitely worth tracking, the “canonic” AAV program in PKU sounds like a low risk bet, their gene editing engine is mor of a mystery to me, not a lot published data but there is something about their vector which makes it super efficient at least in the data they have published. For a 900M market cap, I prefer to wait.

    In EB my rank would be KRYS > ABEO > FCSC but data are still preliminary and hard to compare between studies. KRYS is definitely the most straightforward approach, hope it works.

    I like all the 4 GTx names you mentioned, nothing against them, valuations aren’t cheap, of course.

    Ryan T (AGIO) – I think a lot depends on the MTAP program given the commercial potential and novelty. IDH franchise cannot justify current valuation IMO.

    Eli (BPMC/CMTA) – Sorry, I prefer to avoid discussing FOP and ALK2 inhibitors as I sit on the board of a competing company.

    Colton – I find UBX and RUBY outrageously expensive, a lot of hype but very limited or underwhelming clinical data. MBIO isn’t that expensive but differentiation is a challenge.

    Thome (RGNX/ABEO/BOLD) – Yes, agree these are obvious takeout targets but hard to predict these things. Yes, plan to hold AGTC.

    Dan (ADVM) – I don’t have high hopes for their AMD program and the vector issues they experience with A1AT is a major blow. As you said , their main assets are cash, manufacturing facility and some early stage collaborations.

    Ohad

  121. Hammer u replied to eveeyone but the mgtx guys 👆

    Is it because u want to add 10k shares n4 i do? Lol

  122. Henry – Sorry, don’t know the names well.

    Tom Gathers –
    KNSA – Don’t know them well, a lot of familiar targets targeting less familiar indications.
    KZR- I think immunoproteasome inhibition is a very interesting value proposition and valuation has become more reasonable (still a P1 company). Main challenge is obviously Tx window vs. proteasome inhibitors. So far PD biomarker data looks good, hope they actually found a safe enough dose (45mg) that doesn’t lead to board proteasome inhibition. Still a long way to go but def worth following.

    Les – Thanks.
    CBAY – Don’t know them well.
    XENE – 2019 will be a quiet year for them. P2b data for 1101 is the next big catalyst and it’s more than a year away.

    bouschka (ARVO) – I am still concerned about durability despite signs of stabilization with pt #1, trends aren’t encouraging, absolute AGA levels continue to decrease and VCN values don’t look that great. Hope it will work out for them because the approach makes a lot of sense, perhaps with an optimized product/cond regimen.

    Ohad

  123. Ohad
    Thank you for helping us navigate in the murky bio waters. From educational point of view the blog it top notch. It doesn’t hurt making some bugs along the way either (DMTX, AVXS, FMI, ONCE, NITE) :)
    RYTM has 3 readouts this year. One Ph2 soon and two Ph 3 in Q3, plus another one in mid 2020.
    A sort of the CHMA schedule but with 3× more opportunities and 270M cash.
    What do you think about getting into RYTM before the catalyst this year?

  124. Dan (CANF) – Don’t know this program well but often pushing out OS readout is a negative sign.

    andre (MRNS) – Haven’t looked at them for a while, prefer to stick with SAGE.

    Dave (XENE) – To me 1101 and 901 justify a much higher valuation, I don’t ascribe value to 496.

    Aaron Bairdman (BLUE) – I don’t have an in depth understanding of the tech, still waiting to see clinical programs based on it.

    Kevin P –
    FTSV, TRIL, SURF – So far data for CD47 programs are disappointing imo, still too early to say whether FTSV truly has a differentiated drug.
    Not following allo CAR space closely.

    bouschka – Thanks.

    Les (SEEL) – Sorry, no opinion here.

    Dan – The biology behind ketamine/NMDR is very complex, often with contradicting evidence. I don’t think people were surprised by this failure given the lack of clarity around this class.

    Dan – Sorry, not very familiar with this clinical design.

    Josef (SNSS) – prefer not to comment.

    Chris (AXGT) – Stock is cheap but the PD program isn’t very attractive IMO. Earlier stage pipeline looks more interesting, waiting for their R&D day this month.

    avrofan (AVRO) – Not yet, still waiting for experimental proof they can maintain and stabilize enzyme expression. Not sure current Fabry product is good enough, unfortunately.

    Robert goulet (MGTX) – I think xerostomia is a huge unmet need and very frequent among H&N patients so the potential is significant, should have a dramatic impact on valuation. The NITE deal is clearly a positive for them but data are still too early for both companies. Still didn’t have a chance to look at ABEO’s intravitreal vector, a tough challenge.

    Babi (MGTX) – Now that JNJ owns most ophthalmology pipeline, investors will wait for clinical data but impact on stock won’t be huge imo. The xerostomia program is very interesting but early.

    Ohad

  125. JQ (IMGN) – I understand the concern but it’s important to remember that mirv was compared vs. chemo and not on top of chemo so a the HR >1 in FRa medium patients isn’t that alarming IMO. It just means that the ADC was less effective than an approved chemo regimen, not necessarily fishy.

    Robert goulet (MGTX) – I am still waiting to see data from their programs. The deal with JNJ removed a lot of financial risk but development risk is still there and the stock is at 19 after they basically gave most upside to JNJ.

    andre (RYTM) – Thanks. I like RYTM’s story and the impressive (preliminary) clinical data in niche indications but valuation is too high IMO before seeing an expansion to broader populations like heterozygous MC4R.

    Mike –
    ARPO – Don’t know them well.
    ACIU – Even at current valuation, too high risk for me… Abeta is just a waste of time and money and Tau is not validated.

    Ohad

  126. Hi Ohad
    Re RYTM. Your point is valid – the valuation is a concern. But they are facing 3 readouts in near future and the valuation may never come down, if all good. Plus $250 cash to go through all 3 Ph 3 readouts

    Funny, we were having almost identical exchange about LOXO in October 2015 – pending data and your concern about valuation and market potential :)

    andre on October 14, 2015 at 9:49 pm
    LOXO will present additional Phase I data on LOXO-101, (potentially best in class TRK inhibitor), at next month’s AACR-NCI-EORTC
    Is it a good idea to buy some shares before the meeting? The company is 330M with 100M in cash.

    Ohad on October 15, 2015 at 4:33 pm
    andre (LOXO) –I still think it’s expensive. The drug is still in P1 and market potential is unclear.

    The comparison b/n LOXO and RYTM is clearly not fair, but there are some striking similarities – tiny (initial) population, imprecise efficacy and safety data, clear path to market -if all goes well of course.

  127. IMGN

    I understand that. But previous data showed there wasn’t much difference in ORR between FRa high vs medium, previous line of therapies were more determining factor than FRa high vs medium, thus resulted FORWARD I population and analysis plan. For FRa medium to go completely opposite direction of FRa high mean the whole hypothesis was wrong, either or both set of data unreliable.

  128. Andre,

    LOXO situation completely different because LOXO eventual buyout valuation from LLY came mainly from a completely different drug LOXO-292 than the one you and Ohad discussed in 2015 for LOXO-101.

  129. If or whenever Mr Hammer stop giving advise or opinion,
    I’ll stop investing in Biotech.
    It’s too risky otherwise and will stick to High Tech.

    Thanks for the gains being an amateur here.
    😉

  130. Hi Ohad
    any reasons that CHMA is in a mad up trend?
    are you planning to publish a new post soon?

    Thanks

  131. Hey Ohad,

    Good move by STML licensing that IND ready RET inhibitor? Some people have called it a second generation RET inhibitor. Validated target, so it seems like a great decision.

    Dan

  132. Hey Ohad,
    Great CC by aptose with some peRspective on ARQL restaurants (BTK). I highly recommend it. It also brings up an interesting discussion about targeted drugs vs inhibiting various kinases and rescue pathways.

    Dan

  133. andre (RYTM/LOXO) – You don’t have to rub it in… 😉
    I often underestimate the acquisition values of companies with late stage assets in oncology, plus some companies appear to panic and pay unreasonable amounts for high quality assets. With RYTM I prefer to wait as indications are not oncology so the regulatory route, marketing dynamics and potetnial buyers are different.

    JQ (IMGN) – Previous data were from a small uncontrolled data set. The FORWARD 1 data are more reliable in that sense. It also implies that ORR does not always tell the whole story.
    Mirv’s effect in the FRa medium subset was not opposite to that in FRa high subset because it wasn’t compared to placebo but to an active regimen. It had activity in these pts but effect wasn’t as strong as that of chemo. I don’t think t’s counter-intuitive to have a drug that beats soc in one population but is inferior in another population.

    Alex (CHMA) – No particular reason I could find, they started to receive some analyst coverage, I think I saw an initiation report from Cantor last month.

    Dan (STML) – Agree it’s a good deal providing it’s a selective compound, still haven’t seen the package but the LOXO deal certainly helps.

    Dan (APTO) – Thanks, let’s wait for the data.

    OH

  134. Hi Ohad,

    Thanks for sharing your great insights! Your ability to identify trends and M&A targets is very impressive.

    What do you think about the prospect and valuation of Viewray (VRAY)– a manufacturer of high-definition MR guided oncology radiation equipment maker? Current market cap is more than US$800 M and backlog is about $200 M. 2018 full year revenue was about US$80 M. What is a reasonable price tag for this company in your opinion?

    Link to recent corporate presentation:
    http://investors.viewray.com/static-files/d19e5ae8-3731-4a28-8d13-70fbf968af47

    Another question: do you think its still ok to add CHMA shares at current price? How percentage of acromegaly market can CHMA address? Is their delivery technology applicable to other types of injection-only drugs?

    Best regards,
    Anna

  135. Hi Ohad,
    I’m enjoy reading your blog, thank you very much.
    I have a question on Axsome Therapeutics (AXSM). They just reported a very good phase 2 result of AXS-05 in MDD. They are multiple catalysts in 2019.
    Would you please have a look at it at this current price?
    Thank you,
    Tri

  136. Hey Ohad,
    Similar to Tri I was wondering if you reviews AXSM – their MDD phase two was tested against an active drug- SAGE’s recent test fit port partum depression was placebo controlled. Given the failure of Rapastinel, axsm results are quite impressive. Next huge reading for axs-05 is TRD next quarter.

    Thanks for you replies to my previous questions. Yes, looks like if all goes well APTO 806 will be in the clinic in April and we might see the first data before year end.

    Dan

    Any opinions on valuation and

  137. Regarding KURA:
    Could you assess KURA valuation: potential and compare it to both Nektar NKTR and Mirati MRTX.
    The two latter positions have markedly higher valuations, even with NKTR falling off considerably.
    Is KURA’s potential that dramatically lower?

  138. Regarding VistaGen VTGN:
    Ohad…Dan’s asked about them in recent posts regarding MDD Rx.
    Considering Esketamine’s recent approval, AV-101 from VTGN seems like a natural fit for you.
    It’s an oral agent. Possibly more selective. Esketsmine approval supports interest. Good IP protection. Low valuation.
    It seems to set up similar to PCSK9 v. ESPR story a bit.
    Considering your interest in MDD and pain Rx, why not an interest in AV101?

  139. I am іn tһe process of shopping for some Christmas рresents.
    I am considеring buying Pink Daisy Mesh Chemisze fгom Peaches andd Screms :
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  140. Hey Ohad,

    Re: AXSM
    There are great corporate presentations on their website for AXS-05 by KOLs including dr Fava making a great case why they think the drug works in MDD and should also work for TRD – very compelling presentation (April 2018)- seems the drug is hitting many different meaningful pathways including decreasing inflammation (which is a cause of depression), monomamine signaling, and glutamate signaling which bodes well for its efficacy.

    Dan

  141. Ohad
    Can you elaborate a bit on Protacs. They reminds me of ADC – warhead, linker, etc. What in the Protac construct defines the specificity? How they can be made to target only mutant proteins?
    Thanks

  142. Andre,

    I had the same question about the selectivity of the mutant protein. The answer is three-fold: (1) changing the size and composition of linkers (2) changing the binding ligands to the target protein or E3 ligase and (3) altering the choice of recruited E3 ligases (source: h ttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197674/ – the “h” is broken on purpose in the link). It seems to me there is some flexibility in the approach which make each highly specific and unique.

    There’s a vendor called Promega which can actually map out your ability to penetrate the cell, form a ternary complex with the protein and E3 ligase, ubiquinate the protein, send it over to the proteosome, and then tell if it is degraded or not. If true, would be useful to see if companies are using this to validate the approach and MoA while ensuring that only mutants are targeted.

    The S-1 for Arvinas also has a nice section on selectivity of BRAF mutant and not WT. Check out page 99.

    Nick

  143. Nick,
    thanks for the info and the links. If I am not missing something,
    (1) may not contribute to selectivity in a meaningful way. (3) I don’t think it’s target specific, but rather proteasome related.
    (2) make sense, but finding the proper binding affinity can be a challenge and it can take very long, unless they go with something already known like AR or ER, which they actually do with ARV-110 and ARV-471, respectively.
    Their answer is quite murky (S-1, page 99: “By minimizing the binding of a ligand to off-target proteins and maximizing selectivity for a target protein”)?!?
    Best
    Andre

  144. Andre – that’s right, that is how I am evaluating is also re (2). Yeah the S-1 left a bit to be desired on a couple fronts (ie flexible dosing once the existing protein reservoirs are depleted?? – seems futuristic). I guess we will see when data are read out. I think the tech is cool and I am personally excited to see how the space plays out in cancer, but personally more excited about neuro.

  145. TRVN is moving up. Used to be on Ohad’s portfolio a few months ago. Insiders bought 200K Shares at 1.02 on Feb 1 and it’s now 1.95 with a huge move up today. Just FYI. (I had got out after Ohad’s exit but got in again 😊).

  146. druz – March 27 is their ER date and good news is being anticipated I guess.

    Hi Ohad – you had not looked at FCSC earlier – any update on that?

  147. FCSC – Market Cap is 18.7M, about 19M shares outstanding and volume is 6M today with 159K as average volume… something is brewing. Spiked to $3.28 this morning on huge volume and has dropped to 2.30.

  148. Hey Ohad,

    Seems all the big pharmaceutical cos are entering GTx (Pfizer deal today)- well done on anticipating the market and predicting the maturation of gene therapy! I have just four names in my portfolio ADVM ABEO RGNX AGTC and so I wonder if there are any other GTx cos worth tracking?

    If you look 2-3 years out into the horizon what could be the next big thing to mature / have a similar story?

    Any opinions on VKTX and MDGL – especially vktx with their announcement that the 5mg dose is effective. However they are initiating a phase 2b and are 2 years behind MDGL – what are you predictions for the year for both companies, and have you considered adding MDGL, which is still way down from its high in September.

    And ESPR? Also considering AMRN data?

    Thanks very much for sharing your perspective! Hope you are having a good week!

    Dan

  149. Ohad
    do you have an opinion about peptide based companies like ZEAL
    They claim about their analogs of native peptides: “high selectivity with effects only on the intended target; lower risks of toxicity with limited or no off-target effects”. It looks an unlimited range of possibilities to create drugs “more specific, selective and potent than small molecule drugs”. Sounds great, if true…

    ZEAL has 3 drugs in Ph3, two in Ph 2/1 and is profitable – license fees from SNY and BI. Not sure about valuation – looks not expensive at ~500M. The deal with ALXN looks nice. Very tiny trade volume though – 4K share / day

    The other is much smaller – CWBR. 130M. Ph 1 in NASH and Obesity, currently on hold due to injection site reaction. The same claims for supper selectivity and safety, and broad range of targets.

    Thanks

  150. Hi Ohad, What is your take on AXSM?

    Thanks to the person on this blog that highlighted AXSM (had nibbled at it then)… going great guns especially today after BIIB’s Alzheimer drug failed (added to my position today) and with 5 catalysts this year.

    ADVANCE-1 is AXSM’s trial of AXS-05 in Alzheimer’s disease-related agitation.

    An interim analysis of ADVANCE-1 recently passed which I believe hints at success.

    AXSM’s ASCEND study of AXS-05 in major depressive disorder has succeeded.

    Readouts in treatment-resistant depression, narcolepsy, smoking cessation, and migraine are also due in 2019.

  151. Nice move by VKTX and AXSM, APTO also on the rise—eager to see human data for apto – they claim that excitement about drug is very high and they have already lined up many sites that will come on line as soon as the ind is cleared (sometime next week if all goes according to plan).

    Any opinions on AVNS? A Nature article highlighted the potential of the platform to go after undruggable targets and not cause any mutations, one of the shortcomings of targeted therapeutics / kinase inhibitors.
    Valuations seems reasonable $500M and ph1 was initiated in January.

  152. Ohad

    Since you purchased CHMA the stock doubled and has now pulled back 40%. With its Phase III readout due in the 3rd qtr, do you think it presents a opportunity here. Also, would you give them a 50\50 chance of FDA approval

  153. Ohad
    FCSC – on Mar 27 Ph 3 design for RDEB plus Ph 1/2 data update.
    Expect to start Ph 3 in H1, so they might be in Ph 3 before ABEO
    What would you be looking in the data that can bring confidence to the program.
    I think they may rise money. How about adding FCSC to the RDEB basket (ABEO, KRYS, FCSC) – after secondary or before data?

    AXGT – what do you think of the data they reported 2 weeks ago – in PD and in Tay-Sachs. They rose money already, so they should have enough cash for 2 years.

  154. Anna – Thanks! Not familiar with VRAY but I still plan on holding CHMA into P3 readout (which is obviously a high risk binary event). Market share will obviously depend on their data so it all depends on your assumptions but even as a niche product it can generate 100M so the acquisition value is 500M. Yes, their delivery tech can theoretically be used for other injectibles but I wouldn’t factor in anything at the moment.

    Tri (AXSM) – MDD data look good, my main concern here is the fact they are using generic compounds which shouldn’t prevent them from getting market share completely but it’s a clear overhang and generic competition (on or off label) will surely emerge at some point. I am waiting for the TRD readout.

    Frank (KURA/NKTR/MRTX) – Yes, Kura’s potential is dramatically lower as they target niche oncology indications whereas NKTR (via their BMS collaboration) and MRTX are targeting very big markets. I am not a big fan of NKTR and MRTX at their current valuations. NKTR’s data are hard to interpret with a lot of red flags, smells like the next epacadostat. MRTX is super hyped right now based on hints from AMGN about their KRAS inhibitor which is structurally related to that of MRTX. No plans to add until they show data, especially not at a 2.5B market cap.

    Dave (SEEL) – Sorry, still not familiar with them.

    Frank (VTGN) – These MDD drugs, especially NMDA agents are very tough to crack (see AGN’s recent failure).

    Richard Baker (MRKR) – Don’t know them well but at first blush technology looks complicated, focus on shared antigens doesn’t look that differentiated and clinical data are hard to interpret given trial design.

    andre (PROTAC) – I am far from being an expert in the field, doing work mostly on the VC side… Basically, PROTAC isa molecule with two binding arms, one binds a “disease causing” protein and the other an enzyme that flags that protein for destruction. Selectivity towards a mutated protein can be achieved on paper, not sure it’s feasible in most cases. The main advantages are the fact these molecules can get into cells and are very efficient (low concentrations are needed). Main challenges are designing the right pharmacologic properties and selectivity.

    Nick – Thanks for sharing. In cells it appears these compounds have the right properties, let’s see what happens in humans…. Here safety profile is key because the last thing you want is tempering with proteostasis in healthy tissues.

    Ohad

  155. Les (TRVN) – Stopped following them…

    druz/Les (FCSC) – Nothing I am aware of. As discussed, I prefer ABEO and KRYS as more straightforward approaches.

    Dan (GTx) – Yes, the Pfizer deal is another positive sign but just like ONCE and NITE, it was bought from a position of weakness following a massive series A. Hard to speculate who will be next but BOLD should be on that list for sure providing their data in XLMTM continue to look good.

    Don’t have a particular segment in mind right now.

    VKTX/MDGL – I still intend to hold both, perhaps even add more at the next market dip. Not sure both drugs will make it but MOA is clinically validated.

    ESPR – I still believe it’s a 1B+ drug despite AMRN’s stellar data.

    andre (ZEAL/CWBR) – Sorry don’t know them well.

    Les (AXSM) – Mixed, see above.

    Dan (AVNS) – Sorry don’t know them well.

    Neal B. (CHMA) – Not aware of anything new.

    Dave (CHMA) – I plan to hold going into P3 readout given the current valuation.

    bouschka (VYGR) – My problem here would be investing in a company with an underwhelming lead program but a very interesting early stage pipeline and partnerships. But perhaps worth to reconsider given big pharma’s appetite for GTx as VYGR has very good production and engineering capabilities.

    andre (FCSC) – I don’t know it well enough to add right now but nothing wrond with diversification if you believe in the space.

    AXGT – Encouraging but preliminary, prefer to wait for more data.

    Ohad

  156. Do you have an opinion on GRTS? It’s well below its IPO price. But it’s also very early stage.

  157. Do you follow CymaBay Therapeutics (CBAY)? How does their PPAR agonist- seladelpar, compare with the likes of Madrigal and Viking? (It is now in phase 3 for PBC, and phase 2b for NASH)

  158. Ohad – thanks so much for your insights into various opportunities. I really appreciate your work and input on a number of levels.

    How do you view biolineRx’s stem cell mobilization data?

    Also what’s your opinion on marinus and Ovid therapeutics? I saw marinus signed a supply agreement with Ligand for captisol. This reminds me of sage’s drug, any thoughts?

    Thank you!

  159. Hi Ohad

    Good or bad for Zymeworks with the Atrazenica/Daiichi deal on DS-8201:

    AstraZeneca agreed to pay $1.35 billion upfront as part of a deal potentially worth up $6.9 billion to jointly develop and commercialise Daiichi Sankyo’s antibody-drug conjugate trastuzumab deruxtecan, the companies announced Friday. Along with the upfront payment, which will be paid in two equal instalments, one at closing and the remainder 12 months later, contingent payments of up to $5.55 billion include $3.8 billion linked to regulatory and other milestones, as well as $1.75 billion for sales-related goals.

    /Jens

  160. Hi Ohad
    what is the time line for ESPR?
    does it on a hold until 2022 waiting for the CVOT results?

  161. Hi AVEO/Biodesix just announced early (Phase Ib) results on ficlatuzumab + cytarabine
    in refractory AML. 9/17 patients achieved a CR, and work on identifying biomarkers is ongoing. Are there other treatments now being tested of comparable effectiveness in AML, involving other HGF inhibitors or alternative approaches? Chris

  162. Chris–I was looking at the AVEO data also and Ohad’s take will be interesting. It is a little concerning to me that there was no improvement in CR as they escalated the ficlatuzumab dosing ( 9 of 17 total pts versus 6 of 11 at max dosing). The cytarabine dosing of 2gm/m2 daily for 6 doses is very aggressive (essentially equivalent to HDAC dosing of 3gm/m2 bid day 1,3,5. Their results may not be out of the range of expected hematologic (not molecular) CR with that drug alone…

  163. Ohad…Any thoughts on TCDA. I bought some after the Lancet publication and they bumped after the 40 week data, likely to go down due to public offering.today. Curious as to your thoughts regarding potential if you happen to follow them. Thanks!

  164. Gary, Ohad is not very hopeful for TOCA. I asked his opinion when I was doing DD on them. He’s actually bearish on TOCA.

  165. SGMO Sangamo is all over twitter today validating gene editing.
    Ohad, you had expressed your pessimism on the company and that
    editing is at the very early stage with lots of hype.
    Would this change your opinion now?

    Thanks

  166. DJ–Thanks…I am referring to Triceda, with an oral, non-absorbed medication for metabolic acidosis in CKD (TCDA). Are you referring to that company or Tocagen? I am hoping Ohad isnt too bearish on Triceda, since I have learned that his opinion is almost invariably correct :)

  167. Ohad, ADVM finally hired a new CMO, Aaron Osborne from Genentech. He was previously at Novartis. This seems like a very strong hire. Perhaps a validation of their technology. Does this change your opinion on ADVM’s AMD program at all?

  168. Gary, my apologies, dyslexia kicked in. I commented about Tocagen, as per ym knowldge Ohad never commented on Triceda. B. Regards

  169. Ohad
    You are not a fan of ZFN but what about SGMO just
    as a GT company?
    HemA data look much better than ONCE data, plus a preclinical in Farbi.

    About MGTX – looking into their last presentation I was surprised to see an advanced PD program – Ph 3 ready..
    Ph2 data look solid. Do you see them playing a role in the CNS field?
    Thanks

  170. Hi,

    In terms of Gritstone (GRTS) neon antigen company, what do you think about their Bi-specific antigen platform? Do you like the idea of neon tiger bi specifics?

  171. Hey Ohad,

    What’s your view on Antibiotic/ Bacteriophage/anti infective companies? Any interest in these companies if the sentiment on the space begins to change?

  172. Declan
    Ohad posted this in his last replies

    (MRKR) – Don’t know them well but at first blush technology looks complicated, focus on shared antigens doesn’t look that differentiated and clinical data are hard to interpret given trial design.

  173. Hey Ohad,
    Any opinions on EIGR and their lead molecule which was repurposed from BMS? Will be showing latest data for HDV at this week’s liver conference in Vienna.

    Dan

  174. GNFT looks cheap compared with other NASH companies. An interim analysis of RESOLVE-IT, the pivotal ph3 study of Elafibranor to treat NASH (NAS>=4) and fibrosis (F2 or F3), is expected by the end of 2019. Ohad, what do you think about the French company that just started trading on NASDAQ?

  175. Ohad..Re: MRKR – in a CC about 10 days ago the CEO mentioned “very exciting clinical results” and an “indisputable signal of efficacy” with MultiTAA in their P1 pancreatic cancer trial . He also stated enrollment has accelerated from 10 pts in Dec to 30 pts at the end on March. Now the trial is no longer recruiting (n=45). Thoughts?

  176. Hey Ohad,
    Any opinions on CANF results in CPB – small phase 2, did not show superiority to placebo for overall population (78) but for 56 patients with severe CPB. The trial, similar to CFRX’s, randomized the 9 patients with most advanced and severe disease to the drug arm, and given the small size of the trial this probably skewed results unfavorably. The drug is also being evaluated for NASH with results in q3. Valuation is very low.

    Thanks
    Dan

  177. Hello Ohad,

    Medigene of Germany is interesting: TCR

    In cllinc they are not very advanced, but financially they are very solid. Two deals about 1 billion with market cap Eur 233.

    No risk of increase in share capital.

    Your opinion?

  178. RE: Antibiotic companies — Any thoughts about SPRO (Spero), CDTX (Cidara), NBRV (Nabriva), or PRTK (Paratek). Thanks so much!

  179. $ICPT data released yesterday appears to be misleading or may actually be worse than before. $Icpt has emerging competition and a poor safety/effective profile and needs to raise cash…. haven’t shorted a biotech in a long time but did do today with $icpt

  180. Hey Ohad,

    VKTX showed that it’s NASH candidate is affective at 5mg doses and might go even lower in ph2b – yet the shirts are piling (seems that half the float is short). Any perpspectuve on the short thesis? Do you think this might be a best-in-class drug candidate? And when would a possible BO happen? After the ph2b- so at least one more year away?

    Thanks!
    Dan

  181. One more question!
    Hey Ohad, wondering on the deal by AZN for Daiichi’s candidate Her2 and the implications of this deal for ZYME? Seems like ZYME is undervalued considering the size of the deal.

  182. Hey Ohad,

    I noticed the IPO filing of Hookipa Pharma. Do you know anything about this company and if theirs any similarity between their tech and VBIV. Thx so much!

  183. Ohad, any explanation for why MRUS trades at such a sharp discount to MRTX ($350M mkt cap vs. $2.3B)? I think bulk of MRTX valuation is largely tied to their kinase drug that hits KRAS G12C mutation but is still very early in clinic. MRUS is even further behind in the clinic but claims their wholly-owned MCLA-158 bi-specific (Lgr5xEGFR) also hits the G12C mutation but also hits other KRAS mutations as well. I don’t quite understand the large discrepancy, particularly since MRUS has a broad pipeline of bi-specifics beyond this drug, including a nice partnership with INCY for a CD137xPD-L1 bi-specific where MRUS kept all U.S. rights. Lot of risks still for MRUS as they are very early in the clinic or pre-clinical with all their drugs but I decided to take a gamble.

  184. Ohad
    I am also looking into MRUS.
    Specifically, how do you compare their HER2/3 bispecific (MCLA-158) to ZYME HER2 bispecific (ZW25).
    And in general, how you compare their Biclonics platform to Zymeworks’ Azymetric platform

  185. Hey Ohad.
    any thoughts on SNDX? They have a Menin-MLL inhibitor in preclinic and had a strong financing recently (sold stock with a premium).
    Also: Quizartinib got 3 months review extension by the FDA. PDUFA is August 25 now. A bit surprising for me since they got BTD. Any reason you could think off for the extension?
    Thanks! Ike

  186. Great action on FCSC with their collaboration news following their positive clinical trial news. Any thoughts on valuation? One analyst values it at 10 times current price.

  187. Ohad
    Does the FCSC deal put a price tag on the RDEB? I am surprised that KRYS dropped only 4% today.

  188. Ohad,
    As This current Healthcare correction unfolds, which names, if any, are you targeting to enter into or add to your current positions?
    If Healthcare names retest the Dec ‘18 lows, are you a selective buyer?

  189. Hey Ohad,
    Micro cap MBIO up 400% after hours on lentiviral bubble boy cure. You said market was very small, I think 100 cases a year in USA – but market cap was just $75M and maybe that explains the higher increase – still will have to see how it market reacts tomorrow. However this seems like great news For GTx and research in general as saint Jude (developers of therapy) claims the boys were cured!

    Dan

  190. Article suggest st Jude mightbapply same technology for sickle cell – much larger market

  191. Ohad wherever you are,
    Happy Easter to you and to your loved ones.

    Also, Happy Easter to the blog

  192. Have you ever thought about writing an ebook or guest authoring on other sites?
    I have a blog based upon on the same information you discuss and would really like to have you share some stories/information. I know
    my subscribers would appreciate your work. If you are even remotely interested, feel free
    to send me an email.

  193. Hello Ohad !!! SURE HOPE EVERYTHING IS OKAY !!!! Have not heard from you since MARCH 25th !

  194. Hey Ohad — Do you have any interest in Selecta Bio’s gene therapy platform for re-administering AAV? Also what about Meira GT safety switch tech for gene therapy which allows for expression to be turned on and off?

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