Notes from ASCO 2017 – another year of stagnation

This year’s ASCO marks a second year in a row of relatively uneventful meetings, with very few groundbreaking or practice-changing data. Just like last year’s meeting, there were too many “me too” drugs targeting the same validated targets while results for truly novel MOAs were mostly underwhelming or immature. This stagnation is particularly troubling in light of the huge budgets the industry is pouring into oncology drug development, which used to be a highly capital-efficient sector.

Looking at the different vertical segments, stagnation is apparent across the board with some exception with few kinase inhibitors and BCMA CARs.

Immuno-oncology (IO)

IO continued to dominate the meeting with PD-(L)1 antibodies as a backbone for combination trials. To date, no novel IO agent demonstrated robust single agent activity and this is still the case post-ASCO 2017. While some combination regimens generated interesting signals, efficacy data were mostly limited and immature.

Incyte’s (INCY) IDO inhibitor (epacadostat) was the most prominent IO agent with combination data across multiple tumor types. Keytruda + epacadostat generated a response rate of 33-35% in four tumor types (NSCLC, Head and Neck, bladder and renal cancer), which is numerically higher than the ~20% response rate typically observed in these indications with PD-1 agents alone. These data were the basis for a broad P3 program Incyte is pursuing together Merck. The market is clearly excited about epacadostat, evidenced by Incyte’s $28B market cap (probably more than half of which is ascribed to epacadostat). I find the results hard to interpret given the low sample size (~40 patients per cohort), the complete lack of single agent activity and the fact patients were not heavily pretreated.

Epacadostat

Roche’s/Newlink’s (NLNK) data with their IDO program (navoximod) were underwhelming and led to the termination of the licensing agreement by Roche the following week. This was perceived as a positive for Incyte but it also casts a shadow on IDO as a target, especially in light of the table below Cantor prepared comparing epacadostat with navoximod in heavily pretreated patients, where efficacy appears modest for both agents (small numbers, cross-trial comparison….)

NLNK - Cantor

Beyond Incyte’s data there were almost no notable readouts from a host of PD-1 combination studies. BMS presented combination data for its LAG3 and GITR programs. LAG3+Opdivo demonstrated some efficacy in melanoma PD-1 failures but response rate in the overall population was still just over 10%. Tumors with higher LAG3 expression appeared to be more responsive but this needs to be corroborated.

BMY- LAG3

The GITR study reported responses in 5 (13.5%) of 37 patients with solid tumors. There were no responses with Amgen’s (AMGN) GITR agonist antibody (AMG 228) as monotherapy, similarly to Merck’s GITR programs.

Syndax (SNDX) reported 3 (23%) confirmed responses for its HDAC inhibitor in combination with a PD-1 antibody in a cohort of 13 melanoma patients who had failed PD-1 antibodies. A fourth patient had an unconfirmed response. This response rate appears higher than the typically 10% but the small sample size makes data inconclusive.

SNDX

Corvus (CRVS) presented an update for CPI-444 (A2A inhibitor) in renal cancer. Despite one partial response as monotherapy, overall efficacy was limited with a single-digit response rate in combination with Tecentriq. Celldex’s (CLDX) varilumab (CD27 agonist) demonstrated a ~9% response rate in combination with Opdivo in a mixed population of patients unlikely to respond to PD-1 monotherapy. Jounce (JNCE), which has a market cap of $530M reported P1 data for its ICOS agonist, where no responses were noted in 46 patients who received the drug alone or in combination with Opdivo.

Pfizer’s OX40 agonist demonstrated a response rate of 4% (2/48) as monotherapy. Lilly’s CSF-1R Inhibitor LY3022855 demonstrated no responses as monotherapy, not surprising given prior other CSF1-R programs.  Calithera (CALA) reported data with its arginase inhibitor, which demonstrated strong target engagement but no clinical activity as monotherapy.

The only truly impressive IO data set was for Bluebird’s (BLUE) anti-BCMA CAR in multiple myeloma (bb2121) with a 100% response rate in the 15 patients at therapeutic doses and what is emerging to be excellent durability. This is remarkable given the heavily pre-treated population (median of 7 prior lines).

Kinase inhibitors

There were three remarkable data sets involving kinase inhibitors in niche indications from Roche, Loxo (LOXO) and Blueprint Medicine (BPMC).

Roche presented P3 data for its ALK inhibitor (Alecensa) in 1st line ALK+ lung cancer.  Alecensa was dramatically superior (PFS HR=0.47) to Xalkori, an approved ALK inhibitor from Pfizer. This data set should make Alecensa the agent of choice for 1st line  ALK+ patients, especially in light of the impressive prevention of brain metastases.

ALEX

Loxo reported an impressive 78% response rate for its Trk inhibitor (larotrectinib) in TRK+ solid tumors. Durability of response continues to impress with the vast majority of responders still progression free (median not reached). Strikingly, efficacy was independent of tumor histology and was observed across tumor types. This will probably lead to a broad approval in any TRK-fusion cancer next year.

LOXO - tumor type

Blueprint Medicine reported a 60% response rate for its KIT/PDGFR inhibitor (BLU-285) in PDGFRa+ GIST. Despite the small addressable market (~2000 patients in US+EU), this patient population has no effective treatment alternatives and BLU-285 could reach the market next year based a small P2 study.

BPMC

One interesting study that did not get a lot of attention was Roche’s P2 Lotus study which evaluated its Akt inhibitor (ipatasertib) in 1st line triple-neg breast cancer. The study generated a signal in tumors with dysregulated PI3K/Akt pathway (PFS HR= 0.44) which may be a basis for a P3 in a poorly served patient population (A P3 in prostate cancer just began).

gdc-0068

Akt was once considered a promising target, pursued by many companies but initial clinical data revealed limited efficacy as monotherapy and safety issues. Combining ipatasertib with chemotherapy coupled with a companion diagnostic for patient selection may be the way to realize the potential of Akt inhibitors. Although as single agents, Akt inhibitors are not nearly as effective as ALK or Trk inhibitors, the addressable population is dramatically larger.

This is good news for Array Biopharma (ARRY) which outlicensed ipatasertib to Roche and should be viewed as a positive read-through to ArQule (ARQL) which has two Akt inhibitors in clinical development and is pursuing a similar patient selection strategy.

Antibody platforms

On the antibody front, there was nothing earth shattering with ADCs or bispecific antibodies.

Immunogen (IMGN) presented pooled data for its FRa program (Mirvetuximab Soravtansine) in ovarian cancer, which validated the efficacy signal from last year with a response rate of 47% and a 6.7 month PFS in earlier lines (2nd-4th lines) ovarian cancer. This agent is clearly active but apparently less so in later stage patients, which led Immunogen to pursue approval based on a randomized P3 vs. chemotherapy. Mirvetuximab’s response rate and PFS are numerically higher than what has been seen with various chemotherapies in this setting but relatively low sample size (36 patients) makes it a tough call.

Seattle Genetics (SGEN) and its partner Astellas presented an update for their Nectin-4 program (Enfortumab Vedotin) in bladder cancer. Response rate was 41% in the overall population and a similar level of activity was maintained in PD-(L)1 failures (response rate of 44%). Duration of response and PFS (~4 months) were somewhat disappointing but the overall efficacy profile may enable the companies to pursue approval based on a single-arm P2.

Abbvie (ABBV) presented P1 data for two ADCs based on Seattle Genetics technology targeting cMET and EGFR, respectively. The cMET ADC demonstrated activity with a 21.5% (3/14) response rate. The EGFR ADC generated one PR in 42 patients. Similar to other MMAE-based ADCs, toxicity continues to be an issue as ADCs are still struggling with a narrow therapeutic window. Unfortunately this may also be the case with new payloads, based on Seattle Genetics’ announcement last week about discontinuation of SGN-33A’s P3 in AML.

On the bispecific front, Roche’s anti- CD3/CEA garnered a lot of interest going into the meeting but actual results in colon cancer were mixed. While there was some activity as monotherapy and in combination with atezolizumab (6% and 12%, respectively), it appears to be limited. Personally, I find it hard to get excited by a 12% response rate for a combination regimen but it was encouraging to finally see a bispecific antibody that can be dosed weekly and shrink solid tumors.

CEA=TCB

Merus (MRUS) released initial results for its program HER2XHER3, reporting one (9%) partial response in 11 HER2+ breast cancer.

Portfolio updates –shifting focus to gene therapy

While the mature oncology segment is experiencing R&D productivity issues, the nascent (and risky…) gene therapy segment continues to gain momentum.     

Spark (ONCE) filed its RPE65 product and will likely become the first ever FDA-approved gene therapy. Its hemophelia B program continues to look good with a meaningful and durable clinical effect. Avexis’ (AVXS) data in SMA1 continue to look promising (acknowledging the limited sample size) as the data mature and hopefully manufacturing issues are behind them. Abeona (ABEO) released new data for its Sanfilippo syndrome A program, demonstrating a clear pharmacodynamic effect and preliminary signs of clinical improvement or stabilization (see figure below).

ABEO

In an effort to diversify my exposure to gene therapy I am initiating a new position in AGTC (AGTC) and buying more Abeona (ABEO) and Dimension (DMTX).

Portfolio holdings – June 25, 2017

portfoio - 25-6-2017 - after changesbiotech etfs - 25--6-2017

58 thoughts on “Notes from ASCO 2017 – another year of stagnation

  1. Hi Ohad
    any specific reason ESPR and FMI in an up trend?
    why buy AGTC now? any catalists near term?

    Thanks a lot and glad to see u back

  2. Alex –
    ESPR – It might be related to positive comments from the company on a combination study to be released this week.
    FMI – No idea but stock is very strong given the lack of meaningful newsflow
    AGTC – Next catalyst for them is P1 data in XLRS, 12 patients in the dose escalation portfion with 6+ month follow up. I decided to buy now because the stock is cheap and I believe in their core technology and scientific founders for the long run.
    Thanks!

    Ohad

  3. You indicate BLUE BB2121 data suggests treatment durability. Not true. This is typical BLUE data fraud. Fraud being defined by the SEC as ” it [is} unlawful to disclose any untrue statement of material fact or to omit a material fact that is necessary to prevent statements already made from becoming misleading”.

    The problem (well, one of them) is BLUE knows the BB2121 vector results in response then rapid relapse (average relapse of 12pts 8 weeks after treatment). http://www.bloodjournal.org/content/bloodjournal/128/13/1688.full.pdf?sso-checked=true

    So looking at the BLUE ASCO data, 10 patients reported 6 month data, but BLUE only reported relapse data on 4 patients? When an Ig urine test would easily and quickly identify relapse in less than 8 weeks? Yea. https://twitter.com/stevepluvia/status/873239021018808320

    BLUE knows they have a relapse problem with this vector but wants us to believe they didn’t perform any of the same testing used in the original NCI trial to rapidly identify relapse? Typical BLUE data fraud. They pulled the same crap in their failed gene therapy trials (Sickle Cell, CALD, Thalassemia). Also consider this: Rather than moving to a pivotal trial for bb2121, BLUE is doing a new trial using a new improved bb2121a. GMAFB. Seriously? Why would they do that unless they already know bb2121 relapse makes bb2121 a non starter? Why would they not have relapse data on all of the patients vs a select 4? BLUE is the house of data fraud, buyer beware.

  4. $AGTC unpretentious nerds trying to develop great science…I’ve been in this, sold half on the pop now waiting for another significant dip and going long..in at $5.10

    $DMTX every bio has set backs, they got this out of the way early, plenty left to get this going. in at $1.20

    Ohad, Have u looked in $LPTX? Interesting science, now doing combo with keytruda, float? 3millions shares…near 52 week lows, this could run hard, 25mill in the bank…looking for a nice pop b4 a secondary, I’m a buyer between $5.75-$5.90…in at $6.50

    Also look at former ProNai…$SRRA…$1.17sp with 125mill in the bank! Plenty insiders buys, 60% tute ownership and science derived from the highly reputable ICR in London, SRA7337 has been passed around a bit, but looks like it has application….will by more if it drops again to $1.12-1.14…in at $1.15

    I know u think NK cells lack, but $AFMD’S>> afm13 showed 2 PR’s in 7 patients and now being paired with PD-1….I like the science and think it has significant merit…thoughts?…in at $2.25 and buying all I can at $2.05

    Also $PIRS looks like has huge potential, A. Zeneca just signed a lucrative partnership for their asthma med. curious if you looked into them.

  5. AVEO’s drug Tivozanib has resurrected itself as an effective drug with best tox levels for combination therapy, going for 1st line in renal cancer. Looks like another EXEL story with CABO. Lots of catalysts. Is this stock attractive?

  6. Your view of stagnation is such provocative that I would like to repeat two comments I made earlier to John Carrolls ASCO summary write-up from Endpoints “8 stars: A look back at ASCO spotlights the top cancer drugs to watch, and 1 to forget” (see https://endpts.com/up-8-stars-a-look-back-at-asco-spotlights-the-top-cancer-drugs-to-watch-and-1-to-forget/ ):

    Beside the CAR-T progress (or if you prefer stagnation) in liquid tumors there was noteworthy progress (or you may prefer confirmation) in solid tumors with TCR immunotherapy as well:

    Adaptimmune ( $ADAP ) clinical partners showed the design of ongoing trials for its MAGE-A10 and NY-ESO SPEAR TCR in 7 solid cancer indications. In addition Dr. Sandra D’Angelo of Sloan Ketterring MSKCC presented the latest results of all 4 cohorts from Adaptimmunes NY-ESO-1 TCR trail in synovial sarcoma with responses even in cancers with low (≥ 1+ in ≥ 1% to ≤ 50% cells) NY-ESO-1 antigene expression. (see http://phoenix.corporate-ir.net/phoenix.zhtml?c=253991&p=irol-newsArticle&ID=2278836 )
    With ORR of 50-60% in the target dose the results may not seem to be so eye-catching as CAR-T has shown in some liquid tumors but keep in mind that $ADAP in earlier NY-ESO trials of a liquid tumor (multiple myeloma) also reached over 90% ORR with over 19 month PFS / 3-year overall survival that compares very well with the above $BLUE BCMA CAR-T data (these $GSK partnered NY-ESO-1 TCR data are now to be confirmed and extended with a combination of Mercks Anti-PD1 Keytruda).

    Adaptimmune’s sister company Immunocore is using the same basic affinity enhanced TCR techniques with their BiSpecifics called ImmTACs and showed compelling dose-depending data for a gp100 TCR in an even harder to tread solid cancer of metastatic uveal melanoma at ASCO 2017. (see http://www.immunocore.com/news/2017/06/immunocore-announces-compelling-single-agent-imcgp100-clinical-data-in-metastatic-uveal-melanoma-at-asco-2017-annual-meeting )
    The Immunocore intra-patient dose escalation Phase I IMCgp100 study demonstrated a median PFS of 5.6 months / 6 months PFS rate of 57% which compares so favourably to other clinical studies that Immunocore’s CMO states: “…To our knowledge, no other drug treatments, including checkpoint inhibitors, have demonstrated such positive results in metastatic uveal melanoma before…“.

    Even so these are still early data of small number trials (Adaptimmune 39, Immunocore 19 patients) the TCR pioneers show that antigen targeted immunotherapies are promising for solid tumors via cell as well as BiSpecific approaches.

    As antigen specific patterns rather than cancer indications oriented treatments they also fit well with new biomarker based tumor-agnostic therapies like $LOXO or $MRK.

    From your perspective of stagnation these TCR-developments might not qualify that kind of revolutionary new MoA you awaited for the money flowing into BioTech but perhaps you can agree that the continued focus on immunotherapies over almost 5 years now shows the remarkable shift in cancer therapies that it has already made with checkpoint-inhibitors, oncolytic viruses, immune cell engagers, and first successes in combinations to an even more (r)evolutionary immunotherapy based on gene-edited cells as living drugs started with Denderon’s Provenge to be followed by the now expected approvals of CAR-T and soon TCR T-cell therapies.

  7. Wow, your blog became a braking news!
    Thanks for the very informative ASCO review.
    I had the same feeling and was surprised that the bio stock did not tank after ASCO as it did last year.

    STML update was very positive. 59% CR and no new deaths. It looks 401 is approvalable. Are you still skeptical?

  8. stevepluvia (BLUE) – It’s hard to imagine they would fabricate data in such a way. The Blood paper is wiht a different product from what I can see (NCI’s gamma-retrovirus system).

    robertgoulet – Sorry cannot discuss LPTX, Pontifax is a shareholder.
    Will look at SRRA. I was very excited with Chk1 after ARRY’s deal with Genentech but so far results are disappointing.
    AFMD – Still hard to get excited by their data imo…
    PIRS – I like their pipeline, the only problem is stage, no clinical data in te foreseeable future.

    Don (AVEO) – Agree it’s an interesting story to track but as monotherapy it will be hard for them to take away market share from Opdivo and Cabo without a spectacular data set (why are they using sorafenib as a control again???). The combinability point is an important one imo.

    andre – Thanks. What do you mean by “breaking news”?
    STML – Activity is clearly there but press release doesn’t say much more than that. Need to see full safety profile (including mortality) and response rate in relapsed patients.

    Ohad

    Also $PIRS looks like has huge potential, A. Zeneca just signed a lucrative partnership for their asthma med. curious if you looked into them.

    Don on June 25, 2017 at 3:37 pm said: Edit
    AVEO’s drug Tivozanib has resurrected itself as an effective drug with best tox levels for combination therapy, going for 1st line in renal cancer. Looks like another EXEL story with CABO. Lots of catalysts. Is this stock attractive?

    andre on June 25, 2017 at 7:26 pm said: Edit
    Wow, your blog became a braking news!
    Thanks for the very informative ASCO review.
    I had the same feeling and was surprised that the bio stock did not tank after ASCO as it did last year.

    STML update was very positive. 59% CR and no new deaths. It looks 401 is approvalable. Are you still skeptical?

  9. Dieter Hovekamp – Thanks. Per haps stagnation is too harsh of a word but I certainly feel progress is disappointing in light of the amount of money pouring into cancer drug development. Even if you take Immunocore’s data, which I was really excited with at first (especially in uveal melanoma) efficacy isn’t that impressive after all. I agree that cancer immunotherapy is definitely having an impact and hope next year will have more exciting IO data.

    robert goulet (CALA) – Thanks. Always hard for me to read into this.

    Ohad

  10. >> buying more Abeona (ABEO) and Dimension (DMTX).
    Portfolio shows ADVM ,insted of ABEO

  11. druz – Yahoo Finance automatically groups different positions in the sane line so teh additional ABEO shares (1000)were simply added to the existing one (1200). The ADVM position is an existing one.

    Alex (LPTX) – Merged with Macrocure , thanks Bouschka.

    Ohad

  12. FMI—Some strength in FMI may be due to the LOXO data. The presence of a rare, highly treatable mutation presnt in a tissue-agnostic fashion argues for early molecular profiling in first-line metastatic disease. Up to now, most actionable mutations have been predictable (i.e., EGF-R, Alk in lung cancer) and could be individually tested for. As more drugs like larotrectinib become available, that paradigm may change.

    Ohad–Any thoughts on recent data on Epizyme and tazemetostat in follicular/DLBCL and sarcoma?

  13. Hi Ohad
    Is there a reason why you are keepung TRVN?

    Thx as always
    Christian

  14. AFM24 was shown to be distinguished from cetuximab/erubitux in vitro and in vivo through higher potency at both high and low EGFR expression levels and in RAS mutant cells, while offering a more favorable safety profile. Single and repeat dose toxicology studies in cynomolgus monkeys demonstrated that AFM24 was well-tolerated at high doses. Erubitux sales $687 for 2016

    $afmd

  15. Bouschka (XENE) – Yes… Not sure about what to do next. I think I will either sell or double down given the low valuation and the Genentech collaboration.

    Gary (FMI) – Thanks. That’s an interesting explanation. I still feel it will take more drugs like LOXO101 to turn NGS into standard.

    EPZM – The strong activity in EZH2+ FL was a very nice surprise, especially teh improvement vs.the abstract and the good durability. DLBCL looks less promising but some patients are on teh drug for over a year. Very nice!

    svereb (SGEN) – I think data are good enough for approval and market adoption. Yes I plan on holding.

    Christian (TRVN) – I plan to make a decision by the next portfolio update. Like XENE, still haven’t made up my mind.

    robert goulet (AFMD) – That’s preclinical data. In the clinic we know anti-PD1 is much more active in HL.

    marc frontario (AFMD) – Again, looks good in preclinical studies but need to wait for clinical data. EGFR is not an easy target to work with and prior attempts to have better NK recruitment (glyco-engineerd anti-EGFR) failed in P2 vs. Erbitux.

    Ohad

  16. Ohad. As always thanks for your blog. Very informative. Very bullish on DMTX at these prices too. Vectors come out of the same Dr J Wilson labs as AVXS BOLD VYGR with RGNX as the parent company

  17. Hi Ohad
    any thoughts regarding anacetrapib vs bempedoic acid?
    Maybe a good idea to sell espr for now?
    Thanks

  18. Hi Ohad
    ADVM
    What justifies the company’s market cap? greater then 100M
    All studies Preclinical..

    tnx

  19. Alex……Check ADVM financials. It appears they have over 200 million in cash,or approximately $ 4.89 per share !

  20. Hey Ohad
    Welcome back! Nice to read you again! thanks for those updated.

    What do you think now of MRNS given the huge discrepancy with SAGE. They finally hired someone with a solid background ( their new CMO who just joined in April this year.) I think that is a good move. Valuation is at a dismal $35M, I think this might be a potential acquisition play such as that Canadian company with the JAKAFI competing molecule that GILD bought a few years back (forgot the name), you were an investor.

    IMGN is bouncing back, AVEO bounced back, AUPH bounced back, AERI bounced back big, CLVS bounced back big time, so now I hope XENE TRVN and MRNS are next! What do you think?
    What is your take on SYRS? they are executing and seem to have unique technology and MOA.

    Finally, have you taken another look at LIFE and GEMP and CFRX? What is your take?

    GEMP is going after NASH as well as orphan indication, so after route to market than
    ESPR, I think.

    CFRX is executing, their lysin in in ph2, they have partnerships with leading Lysin research at Rockefeller U, Baker Brothers are big investors, valuation is very low, NIH and FDA are pushing for new meds to fight superbugs.

    Thanks

  21. Hi
    ohad

    Any opinion on EXEL now? Where is this stock heading.

    The independent radiology study results were positive, would like hear what you think of EXEL now.

    Thanks Always

  22. Ohad
    speaking about neoantigen vaccines, I recall you have been positive about GNCA program. They do not have a partner yet but it might come soon considering the increased attention to the field.
    Of course both ADXS and GNCA claim that their algorithm to find “true noeantigens” is superior. Do you have an opinion about that?

  23. Ohad,

    Do you have any thoughts on WAVE (WVE) Life Sciences & their gene editing platform? It hasn’t even moved to the clinic yet but the company itself seems to be very organized and methodical.

    Al

  24. Jaime allen (DMTX) – Thanks! I also feel quite comfortable at these levels, their early programs and know-how could be worth a lot down the road and it’s important to have a broad exposure to the gene Tx sector IMO.

    Alex (ESPR) – Merck’s announcement really took me by surprise, I was expecting ESPR to take a hit but the stock wasn’t hit. It’s hard to assess the threat posed by anacetrapib until we see the data but I agree it’s a concern (despite potential safety issues). I plan to hold my ESPR position for now.

    Alex (ADVM) – Agree their pipeline is early but they have a negative EV and some of their programs (A1AT) look differentiated to me.

    Richard Baker (CTMX) – I still like them and they are making decent progress but price is too high for me without any clinical data.

    Dan (MRNS) – Thanks!
    Agree MRNS is tempting at these levels just based on being a fast follower for SAGE. If SAGE-547 generates positive P3 data in SRSE later this year, they could end up like (YM Biosciences) but they need to show some signal of efficacy.

    SYRS – I like the super-enhancer story but not excited with the RARa agonist. Still waiting to see clinical data.
    LIFE and GEMP – Following them but no strong opinion for now.
    CFRX – Will take a look, I am a strong believer in anti-infectives. Their anti-influenza program is intriguing, it’s about time we’ll have more anti-infective mAbs in development although there are clearly challenges there…

    Dan (QURE) – Their main asset right now is the BMY alliance which is early.

    Ruhu (EXEL) – They are making great progress and it was great to hear CABOSUN readout was confirmed. I still feel the RCC opportunity is priced in, waiting for the liver cancer readout.

    andre (ADXS) – I am very optimistic about neoAgs but not about vaccines. IMO the way to go is with adoptive cell therapies despite the challenging logistics.
    I find the approach in that paper innovative and inteersting but from a cliinical perspective it is hard to conclude anything imo.

    andre (GNCA) – They seem to have a decent platform for experimentally validating true neoantigens. Still early days but definitely worth following.

    Al (WVE) – The technology (or at least what I could undestand) looks really nice, their ability to turn nucleic acids into a more drug-like entities could be very valuable. I am tracking them but valuation is an issue.

    Ohad

  25. ADVM – Ohad, would be curious to hear more about how you think ADVM A1AT program is differentiated. Also, what does competitive landscape for A1AT look like (gene therapy or other)? Not sure if there are other GT players even pursuing this disease. Finally, ADVM seems to be one of the few (only?) GT players pursuing HAE. Curious about your thoughts on that program.

  26. Hey Ohad
    Thanks! Deerfield just took large take in MRNS in latest filing.

    Any news on Ambit’s drug, seems development is rather slow.

    Dan

  27. Ohad…AGTC shitting the bed!! Sunk below 52wk lows on avg. vol
    you still ok with this one?

  28. Also would love to hear your thoughts on AGTC. Still a believer? I continue to believe in this company but I must say its been real hard lately. Stock price continues to get crushed.

  29. Robert and Luigi – AGTC will be data dependent here regardless of how it is getting knocked down right now off very low volume and clearly low interest. Nothing has changed within the company and I assume Ohad’s thesis. If I were you two, I’d learn to size your positions properly. I put a 2% weighting on AGTC so it can go to 0 and it won’t really hurt me. Position sizing is key.

  30. Thanks for the reply. I continue to hold AGTC thru the extended downturn. AGTC promised data this summer. I have bee holding this so long I owe it to myself to see the data.

  31. Any thoughts on Jounce Therapeutics (JNCE), and their 2nd generation immunotherapy pipeline? It is now below IPO levels from Jan., 418.26M Market cap currently.

  32. Hi Ohad,
    Do you follow Srra? Sierra Oncology, would like to hear ur thoughts.. thx
    Chris

  33. andre (QURE) – From what I recall they de-prioritized this program to focus on CNS and CV programs they are pursuing with BMS. I guess that one of the reasons is the fact they use local delivery vs. others (ABEO) that use systemic AAV9 that seem to penetrate the brain efficiently.

    mcbio (ADVM) – What I like most in ADVM is exactly this, the focus on diseases that are currently not aggressively pursued by others. With the A1AT they plan on doing intra-pleural injection, which is unique from what I understand. AGTC and U of Florida had two programs (AAV1 and 2) in A1AT where the virus was injected to the muscle but expression wasn’t high enough. EDIT also have an early stage program but from what I understand ADVM are the most advanced in this indication. Not very familiar with the HAE program but the market is clearly there.

    Dan (AMBT) – Yes it does look like development is slow, hope that patient will pay off eventually, some good progress in AML recently, hope this will be another treatment option.

    Robert Goulet/Luigi (AGTC) – Yes I still plan on holding the stock as I would like to have a broad coverage to the gene therapy segment especially given the low valuation and the fact that subretinal gene therapy is validated by ONCE.

    Al (AGTC) – Completely agree about limiting exposure to a single stock. I personally put the bar a little higher (3-4% for high risk smallcaps) but in emerging fields like GT exposure should be as broad as possible.

    SP (JNCE) – Still think it’s too expensive.

    Chris (SRRA ) – sorry don’t know them well.

    Ohad

  34. Hi Ohad,

    After it’s gain almost 100% in the last 6 weeks, do you think that ABEONA stock still have more upside?

    thanks.

  35. Do you have any thoughts on Omeros (OMER) ?
    I have increased my position even after its strong performance this past year.

  36. Ohad
    who is doing SMA testing for AVXS and BIIB?
    NVTA offers SMA testing for $1500, but I don’t see AVXS or BIIB as their customers.
    NVTA is rapidly increasing the revenue and decreasing COGS, so they may become profitable before FMI.
    How do you compare / value both companies.
    Thanks

  37. Thoughts on Sophiris SPHS? Interesting trial going on into the area of prostate cancer. Any feedback would be greatly appreciated

  38. Ohad picked up some WVE during the recent dip mid 16 range. Love the science and pipeline. Peter K with RA whom I respect is betting the farm on this company.
    they are in the clinic now and we shall see however looking at the pre-clinical data I like what I see. secret sauce appears to be exacting specific chemical structure of Oligonucleotides into drug modality with high specificity/target engagement to silence mutant gene. could really run if data shows efficacy and is safe.

  39. Ttph

    Positive top line results from ph 3 trial. Do you like the stock at current valuation

  40. Hey Ohad.
    Have you looked at SRRA and do you have an Opinion on CHK-Inhibitors as a class?
    Thanks

  41. NM (ABEO) – Yes I still think it has more upside providing clinical data continue to look good.

    Lawrence (OMER) – Haven’t looked at them for a while. They had an interesting complement program at the time, not sure what happened to it…

    Alex (GNCA) – Sorry, no strong opinion there.

    andre (AVXS) – Don’t know about the Dx tests each company uses. I typically prefer to focus on therapeutics, for me FMI was an exception…

    Luigi (SPHS) – Sorry , don’t know them.

    Jaime Allen (WVE) – Agree their platform is very exciting scientifically speaking but valuation is still an issue imo.

    Franz (TTPH) – Still didn’t have a chance to review the data.

    Ike (SRRA) – CHK used to be a very hot target but clinical data was disappointing. Genentech and Array had 2 candidates that were terminated.

    Robert (APVO) – They have a couple of interesting bispecifics but hard to get excited with CD3 based constructs based on data so far.

    Ohad

  42. Hello Ohad,

    isn’t it now a good opportunity to buy BLCM? Especially when you compare the market capitalisation with other CAR-T companies. BLCM has some special features (e.g. safety switch technology). 501 far advanced. 601 interesting approach to kill solid tumors. 701 TCR.

    Thanks Toby

  43. Ohad,

    At the end of the 3rd quarter, ARQL will have about one quarter of cash left. They have to do another raise with heavy dilution at close to a buck a share. Not good. What are your thoughts now on ARQL?

  44. ARQL – At June 30, 2017, the company had a total of approximately $31,007,000 in cash equivalents and marketable securities.
    not much.. what do you think?

    Thanks

  45. Hi,

    Thanks very much for sharing your knowledge. Do you have any comments about VYGR’s latest results for CNS disease or MYOK’s data? MYOK also seems to be working on gene therapy (for heritable cardiovascular diseases) and has prominent scientists onboard. Thanks.

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