Top picks for ASH 2013

The annual ASH (American society of hematology) meeting will take place next month in New Orleans. Based on the abstracts that were released 2 weeks ago, it seems that after 2 phenomenal years of introducing novel mechanisms, this year’s meeting is going to be more on the evolving landscape in each segment (Btk/PI3K inhibitors, antibody drug conjugates, myelofibrosis, CD38 antibodies, chimeric antigen receptors etc.).

Below are my top picks.  

Infinity – Still trying to differentiate IPI-145

Infinity (INFI) had a great meeting last year at ASH 2012 but investor sentiment took a 180 degree turn in 2013 and the stock is down 70% from its peak in April. Although everybody agrees Infinity’s isoform-selective PI3K inhibitor, IPI-145, is active across multiple indications, there is skepticism regarding competition as well as safety concerns.

At this year’s meeting, Infinity will present data for IPI-145 in CLL, indolent NHL and T cell lymphomas. The CLL data set will be at the center of attention, as it will be compared to competing drugs, particularly Gilead’s (GILD) idelalisib (also a PI3K inhibitor) and   Pharmacyclics'(PCYC) ibrutinib (brand name Imbruvica).

In order to do regain the market’s trust Infinity must convince investors that:

1- There is a place for PI3K inhibitors alongside ibrutinib

2- IPI-145 is truly differentiated from Gilead’s idelalisib

3- There is no increased rate of infections with IPI-145 compared to other drugs

According to the abstract, response rate (52-53%) was in line with the prior update in June (55%), which is not surprising given that the abstracts were submitted in July. Actual data at ASH will include more patients, higher doses and longer follow up.

The response rate continues to look numerically better than idelalisib (~40%) and lower than ibrutinib (~70%). In order to differentiate IPI-145 from idelalisib, response rate needs to improve to 60%. This, together with quicker onset of response and potentially better CR rate, should be sufficient to position IPI-145 as a best in class PI3K inhibitor.

The company hopes that with more follow up, response rate will increase as a result of longer treatment duration that may lead some of the nodal responses to convert to full blown responses. This was also the case with Idelalisib which had an initial response rate of 26%. To date, this has not materialized but the constant addition of new patients with limited follow up may have contributed to that.

From a safety perspective, Infinity has to show a comparable risk of respiratory and infectious adverse events. The company implemented preventive anti-infective treatment earlier this year, so it will be interesting to see whether rate of infections decrease in newly recruited patients.

A small cohort of ibrutinib-failures will also be presented. Any signs of activity in this subset could be critical for IPI-145’s positioning in CLL. Responses may create an important near term commercial opportunity (albeit relatively small) and a validation for PI3K inhibitors in general.

There are multiple isoform-selective PI3K inhibitors in development. These include a 2nd-generation molecule from Gilead (GS-9820), Amgen’s (AMGN) AMG319, Incyte’s (INCY) INCB40093 and TG Therapeutics’ (TGTX) TGR-1202. Some of these compounds will have data at ASH.

According to the abstract, GS-9820 demonstrated early signs of activity with no liver toxicity. AMG319 has early but promising activity, with lymph node reductions across all 21 CLL patients and what appear to be responses in 7 patients. Importantly, all 7 received a higher dose.  No activity was observed with TG therapeutics’ TGR-1202, but the company will report data with higher doses at ASH. It is important to note that the drugs above are only delta-selective as opposed to IPI-145, which is a gamma/delta inhibitor.

The fact other companies are pursuing PI3K inhibitors is encouraging as it implies these companies still believe in the relevance of this class of drugs in the ibrutinib era.

Pharmacyclics – Ono as an emerging competitor             

Pharmacyclics’ Imbruvica is still the undisputed leader in B cell malignancies, with a high likelihood of becoming a $5B+ drug. Fortunately for Pharmacyclics, there are very few other Btk inhibitors in development, the most advanced being Celgene’s (CELG) CC-292, which could not replicate ibrutinib’s strong efficacy. At ASH, Celgene will present updated results that look better but the drug’s clinical profile (safety/efficacy) still looks inferior. This explains Celgene’s strategy to pursue CC-292 in combinations in contrast to Imbruvica, which was initially pursued as monotherapy.

Japan-based Ono will have results for its Btk inhibitor, which appears promising based on preliminary efficacy mentioned in the abstracts. In CLL, 7/10 patients had a nodal response including 2 PRs whereas 3/6 MCL patients experienced a PR. Even if Ono’s Btk inhibitor proves to be comparable to ibrutinib, it still trails in development by at least 2 years. As ibrutinib will become approved in all the major indications within 1-2 years, Ono will have to run comparative trials to demonstrate its drug’s non-inferiority. In some indications, these trials will take years to read out.

Incyte – Focus on competitive landscape

At this year’s ASH, investor focus will be more on potential competition rather than data for Jakafi.  Incyte (INCY) will present updated survival data from its pivotal trials, which continue to show a clear separation of the curves with good statistical values. Hazard ratios deteriorated a bit but the signal is still impressive given the fact both trials were not designed to assess survival and the cross-over of patients from the control arm to Jakafi.

Activity for Incyte’s selective Jak1 (INCB39110) inhibitor in myelofibrosis (MF) appears underwhelming which implies that Jak2 inhibition is required for clinical improvement. This should not have a major impact on this program’s prospects as the main value is still in autoimmune diseases, particularly in RA. The hematologic side effects are concerning and look more prevalent than other Jak1-selective inhibitors but this may be related to the disease itself rather than the drug. As a reminder, Galapagos’ Jak1-selective inhibitor was partnered with Abbvie (ABBV) in a huge deal that included a $150M upfront payment.

Sanofi (SNY) will present phase III data for its Jak1/2 inhibitor, fedratinib, which is Jakafi’s most advanced competitor. Fedratinib demonstrated good activity measured by spleen volume and symptom relief but appears to have more safety issues than Jakafi. Given a better overall clinical profile, it looks like Jakafi will remain the dominant Jak inhibitor for at least 2 more years. Next challenge will be from Gilead’s momelotinib, which just started a head to head phase III vs. Jakafi. The trial is designed to show superiority in terms of anemia with a comparable effect on spleen size and symptoms.

Geron – a potential disease modifying agent for MF

Geron (GERN) will have an intriguing data set for imetelstat in MF, which is already spurring controversy. Geron is trying to position imetelstat as the first disease-modifying MF drug based on promising effect in the bone marrow. According to the abstract, of the 18 patients who were on the drug for at least 3 months, 4 had a complete response according to bone marrow biopsies and blood tests. This activity is not seen with Jakafi or other Jak inhibitors, which are viewed more as symptomatic anti-inflammatory drugs.

Imetelstat’s effect is very intriguing and suggests the drug may treat the underlying disease (Fibrosis in the bone marrow caused by aberrant cell growth), rather than its symptoms. Still, results are preliminary and a lot of information is missing (response durability, reduction in spleen size, constitutional symptoms), so the updated results will be crucial in understanding the drug’s potential in MF. Imetelstat’s safety profile and the fact it has to be given IV are 2 additional issues.

Interestingly, imetelstat’s data set comes from Mayo Clinic’s Ayalew Tefferi, the same clinician who did the initial trial for YM Biosciences’ (now part of Gilead) momelotinib (CYT387). At the 2011 and 2012 ASH meetings, momelotinib’s unexplained anemia effect led some to speculate it may displace Incyte’s Jakafi although most were skeptical. This year, Tefferi comes to ASH with another potential “Jakafi-killer” but this time with a potential disease modifier.

Seattle Genetics – Internal and partnered pipeline advance

For Seattle Genetics (SGEN), this year’s ASH will be all about DLBCL, an aggressive lymphoma subtype which represents a highly unmet need with no meaningful advances since 2006 (Rituxan’s approval). Investigators will present updated phase II for the company’s Adcteris and for Genentech’s CD22 and CD79b antibody drug conjugates (ADCs).

According to the abstracts, all 3 ADCs have good activity in DLBCL with response rates of:

1-  40% (16% CR) for Adcetris

2-  41% (17% CR) for CD22 ADC

3-  48% (10% CR) for CD79b ADC

Adcetris appears to have the best clinical profile with a high number of CRs, good response durability (8+ months) and a manageable safety profile in a truly refractory patient population although less heavily pretreated. Obviously, this may change at ASH with updated results for the 3 programs.

There is still open questions regarding Adcetris in DLBCL, including the importance of CD30 expression for patient selection (initially targeted CD30+ DLBCL but activity is seen also with minimal CD30 expression) and the approval route in DLBCL. Some believe Adcetris’ activity may be sufficient for compendia listing or even accelerated approval.

Amgen will also present data for blinatumomab, a bispecific CD3XCD19 antibody, in DLBCL. The abstract discloses responses in 4 out of 7 patients (57%) with limited follow up.

Adcetris will also have updated results in CTCL, where response rate increased to 71% (was 65% at the last update).

Early data for SGN-19A, an anti-CD19 ADC, will also be presented. The abstract includes only lower doses and a complete response in ALL. It remains to be seen whether SGN-19A is differentiated from other CD19 antibodies and ADCs.

Genmab – Main focus still on Arzerra, but should be on daratumumab

Genmab’s (GEN.CO) shares have come under pressure after data release for Roche’s Gazyva (GA-101) in CLL. Gazyva, a glyco-engineered CD20 antibody is the biggest threat to Genmab/GSK’s  CD20 antibody, Arzerra. Both companies will present phase III results in 1st line CLL.

Gazyva’s abstract reveals impressive activity and most importantly for Roche, clear superiority over Rituxan. Gazyva led to almost a year’s difference (26.7 vs. 15.2 months) in PFS, which is even more impressive given the fact that the control arm received chemotherapy and Rituxan. CR (21% vs. 7%) and minimal residual disease (29.4% vs. 2.5%) rates were also significantly better for Gazyva.

Arzerra’s phase III evaluated Arzerra+chemotherapy to chemotherapy alone and generated PFS and CR values that appear numerically inferior (cross trial comparison). Arzerra demonstrated  a PFS of 22.4 months and a CR rate of 12%. Hazard ratio also appears inferior to Gazyva’s past performance versus chemotherapy alone (0.57 vs. 0.16).

Genmab claims that the market’s conclusion about Gazyva’s superiority is not based on an apples-to-apples comparison. With respect to PFS and CR, Gazyva’s results are based on investigator assessment while Arzerra’s data are based on a blinded independent review. According to Genmab, it will present also investigator-reviewed PFS and CR rate which will be numerically higher than Gazyva’s data. Safety profile also appears milder with Arzerra, but it is unclear how much weight is given to this aspect in light of the impressive efficacy.

Regardless of the Gazyva-Arzerra debate, investors’ focus should shift to daratumumab (anti-CD38), which represents Genmab’s most important growth opportunity. Genmab will present initial results from a combination trial for daratumumab and Revlimid. The abstract is scarce in details but it appears the combination is safe and active. A response rate below 80% should be regarded as disappointing.

The more intriguing CD38 data set will come from Sanofi’s CD38 antibody (SAR650984, licensed from Immunogen [IMGN]), for which Genmab’s investors should pay close attention.  Although it is hard to compare SAR650984 to daratumumab based on the limited data in the abstract, the abstract has clear signs of activity in multiple myeloma. In addition, activity looks dose dependent with 4/9 (44%!) patients treated at the 2 higher doses achieving a PR. This is comparable to daratumumab’s response rate, but depth and durability of responses is unknown.

This is a positive for Immunogen, whose investors are looking for additional revenue generating assets beyond Kadcyla (T-DM1). For Genmab, SAR650984’s results suggest daratumumab will compete with other CD38 antibodies but they also validate CD38 as a target. (I previously discussed the CD38 landscape here). Sanofi already started a Revlimid combination trial for SAR650984 but did not disclose long term plans for the program. In order to be competitive, it must accelerate the development program as J&J (JNJ), Genmab’s partner, is putting  a tremendous amount of resources behind daratumumab.

In contrast to prior expectations, Celgene/Morphosys (MOR.DE) will not present results for their anti-CD38 antibody, MOR202.

Array – Update on ARRY-520 and ARRY-614

Array Biopharma (ARRY) will present updated results for ARRY-520 in multiple myeloma and more interestingly, about the utility of AAG level as a patient-selection biomarker.

A study evaluating ARRY-520 alone or with dexamethasone demonstrated a response rate of 16% for both regimens with response duration of 8.6 months in the monotherapy arm. In patients with low levels of AAG in the blood, response rates were 23-24% vs. 0% in AAG-high patients. Results continue to suggest that AAG as a biomarker could identify a patient population for which approval can be obtained with a single arm phase II.  Importantly, the abstract includes a fairly large sample size (82 patients), which should be considered more reliable than last year’s update (45 patients).

Acknowledging ARR-520’s efficacy, it is important to note that only half of the patients in the monotherapy arm were double-refractory (to Revlimid and Velcade). In addition, ARRY-520 does not look as active as CD38 antibodies and it also has a high frequency of bone marrow toxicities.

According to the abstracts for the Kyprolis and Velcade combinations, the two regimens clearly have activity but it is hard to tell whether ARRY-520 leads to a significant improvement. The Kyprolis abstract reports a response rate of 37% (7/19) and the Velcade abstract reports a response rate of 31% in 13 patients who were given higher doses of the drugs. These response rates are numerically superior to what could be expected with monotherapy Kyprolis and Velcade but the difference does not appear dramatic (~10-15% absolute improvement).

Array will also present data for a new formulation of ARRY-614 in myelodysplastic syndrome (MDS). The abstract discloses proof of target inhibition in the bone marrow and signs of efficacy as defined by a hematologic Improvement   in 12/54 evaluable patients.  At ASH, ARRY-614’s potential may become apparent with additional data for clinically relevant doses and guidance from Array on regulatory strategy for the drug based on interaction with the FDA.

Ambit – As expected, strong AML data

Ambit (AMBI) will present important data for its Flt3 inhibitor in AML as single agent and in combination with standard treatment regimens. The monotherapy data will shed light on quizartinib’s efficacy at lower doses (30/60 mg) and whether these doses are associated with less side effects (especially cardiovascular). The monotherapy data may be used for obtaining accelerated approval whereas the combinations will be the basis for a broad registration program.

In the monotherapy trial (76 patients), both doses induced a CRc rate of 50% with the vast majority of patients achieving CRi (incomplete hematologic recovery). 29%-37% of patients were bridged to stem cell transplant, which is considered the ideal therapeutic option in AML. This data set is in line with expectations and despite the low number of full CRs, quizartinib is still the most promising AML agent in development. Nevertheless, it is still unclear whether the results are sufficient for accelerated approval (discussed here).

When compared with these results, Epizyme’s recent phase I update in AML looks unimpressive.

 Stemline – Robust activity in rare tumor   

Stemline (STML) will present updated results for SL-401 in BPDCN (blastic plasmacytoid dendritic cell neoplasm), a rare cancer type with no approved treatments. The abstract includes 5 evaluable patients, all of whom achieved a response including 4 who achieved a CR after a single treatment cycle. SL-401’s activity coupled with the unmet need and rarity of BPDCN implies a very high likelihood of approval based a single arm phase II. The main issue with this drug is whether it can be given chronically, due to immunogenicity.

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75 thoughts on “Top picks for ASH 2013

  1. For some reason ,it is always hard for me to assess MDS drugs, especially when results are from non-randomized trials. In any case, I understand high-risk MDS data is around the corner.

    Ohad

  2. Thanks, Zack.
    There is no doubt SL-401 has an impressive immediate effect, the problem is maintaining responses with more treatment cycles. The re-treatment case they describe is encouraging because it demonstrates a good safety profile but it also demonstrates durability issues (relapse within 3 months of prior cycle) and decreased efficacy (patient had an improvement but was unable to achieve a response and progressed). I acknowledge this is a tough case and 2-3 immediate treatment cycles may produce better results.
    My biggest concern is generation of neutralizing antibodies against the toxin moiety, perhaps this can explain the decrease in efficacy.

    Ohad

  3. Ohad

    You are so balanced as a writer. Always thoughtful. Like your notes on $ambi and $stml. I am long both.

  4. Thanks, Bridgette. It’s always good to be familiar with the drawbacks of the stocks you like. AMBI will have a crucial FDA meeting later this month which could have significant implications (good or bad).

    Ohad

  5. Interesting, the write up on ARRY does not appear to make it look like a potential ASH top pick

  6. In your earlier comments on Agios I perceived you to be Very impressed with their technology.What price would you feel would be an attractive entry point?

  7. Hi Ohad,

    what do you think about french based Innate-Pharma. Actually, they have 5 drug candidates in development. The last of them was added last Friday – it’s an anti-mica antibody. Never seen this target before. Do you know anything about it and what do you think about the company.
    Think about buying some shares.

    Thank you!

  8. Robert – I am more cautious on ARRY-520 given the competitive landscape but the AAG data is very intriguing. I am bothered by the fact this biomarker has nothing to do with the biology of the tumor but to the drug’s availability in the blood.

    Alex65 – Yes results in statin intolerant patients look good but they are not new.

    Bouschka3 – Right, I am very impressed by AGIO’s approach and preclinical data. I still think they are too expensive, price has to go 40-50% for an attractive entry point imo.

    Martin – They had an impressive deal with BMS, who knows a thing or 2 in immunomodulatory drugs. Personally I wasn’t impressed with their data but they are working on combinations for their KIR antibody with other immune checkpoint blockers. Saw the MICA poster they presented at SITC, the activity they show isn’t phenomenal imo.

    Ohad

  9. Ohad – Have you looked at KPT330, a novel Selective Inhibitors of Nuclear Export or SINE XPO1? ASH abstracts show the drug clearly has activities. AE profile is a little bit tough relative to other oral agents in the same space, but seems manageable. Never heard of this target until recent KPTI IPO.

  10. JQ- Agree, interesting signs of efficacy, especially in the ibrutinib failure CLL patient and the DLBCL patient. They also had activity in AML. I would wait for more data to get a better sense of the safety/efficacy profile. The drug looks less safe than other orals in NHL and CLL but if activity in last line patients is demonstrated in additional patients it could be an interesting salvage treatment.

    Ohad

  11. No regarding both. ARQL is a high risk bet following the NSCLC failure and the dose reduction in HCC. I like their low market cap plus 2 early stage programs (Akt +FGFR) but I want to have a limited exposure.
    ESPR – Feel comfortable with a small position at this stage. The drug works but follow up in these indications is crucial for safety purposes.

    Ohad

  12. Hey Ohad ….are you tracking CLVS by any chance ? What is a good entry point in your opinion ? Thanks !

  13. Ohad: On ARQL, not sure if you listened to most recent CC and were aware but ARQL disclosed a lot during that CC with respect to the dosing issues with tivantinib in P3 HCC. A lot of the problem they believe appears to be due to the switch from use of tivantinib in capsule form in P2 to the new tablet form used in P3 HCC trial. ARQL disclosed during last CC that 120mg tablet they are using now in P3 HCC trial is similar to the exposure of the drug seen with the 240mg capsule used in the P2 trial. If true, hopefully results with 120mg tablet can also be similar to what we saw with 240mg capsule in P2 HCC (which was quite good). Obviously no guarantees, but I’m not giving up on P3 HCC trial just yet and otherwise am still long ARQL for better or worse.

  14. Interesting point on 520 with aag….I will go back to an earlier prediction…I think it will all come down to the mek’s with ARRY(late stage)…I have tempered my enthusiasm for this stock, may move more of my holdings into EXEL since I have huge confidence in cabo for another indication

  15. Neo – CLVS did a brilliant deal and I plan on adding them to the portfolio. The drug they bought has a strong clinical proof of concept with a differentiated profile and a clear development lead. Well done Clovis!

    mcbio – Thanks for the update, wasn’t aware of that. Still high risk imo…

    Robert – Agree the MEK franchise is more exciting (albeit partnered). What do you mean by “another indication”?
    Re GDC0973 – thanks, very surprising they are going after KRAS. Perhaps it was too early to judge

    Steve – See above. I am not that excited about their pipeline but BMS clearly are

    Ohad

  16. When I said (other indication) I was referring to exel’s cabo….arry is my largest holding…but after seeing some of the limitations of arry late stage compounds I will reallocate funds from them to make exel my largest holding because I believe cabo will achieve another indication…either for prostate, hcc or renal plus cobimetinib….future looks bright regardless of the amount of outstanding shares

  17. Hi Ohad, regarding lucitanib CLVS stated that its a pure dual FGFR + VEGFR inhibitor. But EOS previous presentations also indicate strong inhibition of CSF-1R. Thus I wonder if lucitanib has direct immunomodulation properties (downregulation of TAMs) resulting in long lasting benefits beside FGFR1 inhibition… i.e. something like ARRY/CELGs cFMS-inhibitor ARRY-382 (shelved bc of the small therapeutic window?) or AMBIs preclinical CSF-1R inhibitor AC708? What is your opinion? Many thanks!

  18. Any thoughts on MEK + PD1 combi?… Roche just has started a MPDL3280A PI with Cobimetinib. In preclinical models PDL1 bypassed possible immunosuppression caused by MEK inhibition lead to synergetic effects. Some models showed up to 60% CR.

  19. Innate Pharma – could KIR-mab + naked antibody (e.g. CD20, HER2,…) combinations offer same value by boosting ADCC?

  20. Ohad,
    do you have an opinion about FPRX. IPO price was $13, now they are at $7. Marketcap $144 Mio. Total stockholders’ equity is $64 Mio. Probably the valuation is still to high.
    Toby

  21. Any thoughts about THLD? Novel MoA (hypoxia targeting), encouraging PII results, in two PIII trials (soft tissue sarcoma and pancreatic cancer). Both indications partnered with Merck Serono.

  22. Ohad,

    What do you think of TGTX? Market cap is only $123 million with about $45 million in cash. Low burn rate. Brean has a price target of $13. The pipeline looks interesting in hematological malignancies.

  23. ipollit – You can never know for sure whether another mechanism is involved in clinical activity but in this case the pronounced activity of lucitanib in FGFR1 amplified tumors that progressed on FGFR selective inhibitors lead me to assume that the effect seen to date stems from dual VEGF/FGF pathway inhibition. Nevertheless, since the drug has a low IC50 for CSF1R (5nM), CSF1R inhibition is probably taking place in patients. Thanks for bringing that up, interesting point.

    Re: cobimetinib +PDL1 – that’s a very intriguing initiative that still looks somewhat challenging to me. Administration intervals will have to be closely monitored.
    Re: Innate pharma – theoretically yes since anti-KIR abs enhance NK activity, which is needed for good ADCC.

    Christian and Chris – Don’t really know. On the face of it it’s negative since the guy led so many discovery campaigns within Array and is a prolific scientist. It shouldn’t affect late stage programs.

    Toby – I like FPRX’s approach scientifically but to date clinical development for their FGF trap was slow and p1 results weren’t impressive. As with other biotech IPOs I prefer waiting for markets to cool down.

    Mike – THLD’s approach is attractive but to me their data have positive signals but not as compelling as I hoped them to be. I was particularly disappointed by the modest monotherapy activity. The strongest piece of data in the randomized p2 in panc cancer but there they’ll compete with Abraxane, which is already approved and the survival data was problematic (no statistical significance although 1ry endpoint was PFS and was met).

    Richard – imo TGTX’s value lies exclusively in the PI3K-delta program (the CD20 program is worthless). As a fast follower, it may have some value but competition is very strong (see INFI) and so far the abstract doesn’t show activity in fairly high doses.

    Robert – More intrigued than excited 😉 I guess there is sufficient experimental evidence supporting this combination but it may still be a tough one.

    Christian – Waiting to hear CLDX’s webcast tomorrow but as always their results with rindo are mixed to positive and very preliminary. The good news – there is a survival signal in a randomized trial (for the first time with rindo!) but in a small sample size (n=40). Statistical trend looks ok relatively and teh correlation in an immune response is intriguing. The Avastin combination data were a little bit disappointing to me, in any case it is hard to disnguish between rindo’s activity and that of Avastin although in some cases patients were truly refractory to Avastin.

    Ohad

  24. Ohad, have to disagree on TGTX. Not sure why you see their CD20 program as worthless. They have already shown CRs in Rituxan-refractory patients. Also, on the PI3K-delta, they have said they are only just now getting to the point where they expect to see activity and I believe that data will be presented at actual ASH presentation. Finally, there is rationale for their CD20 in combo w/PI3K, not to mention other agents (e.g., they plan to run trial in combo with ibrutinib).

    P.S. I don’t get why people are still excited about CLDX here at $2.3B market cap. Risk-reward has changed considerably from back in the day when valuation was sub-$500M and I don’t think story has changed much at all since that time.

  25. Mcbio- TGTX’s CD20 antibody has zero chances to grab market share from rituxan arzerra or gazyva unless it proves to be superior to all which will take years and hundreds of millions to prove, and let’s not forget all the new treatments that are going to be approved.
    Regarding the pi3k program, let’s wait for ASH

    Agree that CLDX isn’t cheap, the stock’s move does represent fundamental progress with all programs but valuation is high.

    Ohad

  26. Ohad, on TGTX CD20, TGTX claims they are pursuing third line patients and therefore not really aiming to compete directly with rituxan, arzerra, or gazyva. They are content to let those other drugs handle first two lines and be content with salvage setting; TGTX doesn’t need a lot of sales most likely to move dial at this small valuation. Obviously still plenty of risks and no guarantees drug will even make it to market but I will hold.

  27. Hi Ohad,
    As always want to let you know how helpful your comments and allowing us users a forum to interact are to investing in this space, thanks for all your efforts.
    As far as expanding beyond oncology I am wondering if you’ve given any thought to regenerative bio-med companies? There are a few out there (i.e. ATHX; CYTX; IMUC, full disclosure I am long all) and I think there is some overlap with the cancer stem cell specialists, to a degree. Curious to hear your thoughts.
    Jeff

  28. mcbio – I am not ruling out the opportunity as a salvage therapy, I am just not convinced TGTX’s antibody can be so effective after all these abs failed. How strong is TGTX’s data in Rituxan-REFRATORY (not just relapsed) patients?
    Btw, from what I recall retreatment with rituxan has activity.

    Jeff – Thanks. Unfortunately I am not familiar with the field. btw, why do you include IMUC as a regenerative company ?

    Ohad

  29. re Regenerative Companies
    Ohad, all,
    My apologies on including IMUC with regenerative group which is clearly erroneous, faulty memory at work.
    Other companies that are recognized in the field for any who are curious (none of which I am long): ASTM; BTX; NBS; CXMI; ACTC; CUR; OSIR; PSTI; MSB.
    The technologies seem quite interesting and I admire the thought and knowledge that is expressed by you and your readers if anyone finds this area of interest.
    thanks again.
    Jeff

  30. The CTO for ARRY is probably related to the departure of Kevin Koch and contingent executive compensation. As for ESPR, I dipped in couple of days ago as well :-( based on oversold conditions. That space is rife with problems (ex AMRN) related to data and the need for it to support cardiac outcomes. Ohad at what price would you dip into AGIO. 50% discount to its IPO right now.

  31. Manish: I looked into CTO and it’s related to prior deal w/CELG on pre-clinical asset. Probably just don’t want certain specific terms revealed. Doesn’t pertain at all to any of ARRY’s key assets today (IMO): MEKs, 520, or 614.

  32. Hey Ohad
    have you listened to the CLDX conference on Rindo? did it clarify some things to you?

    Also, what is your opinion on TTPH, which receltly completed a placement for $59M and is poised for p3 results? Their antibiotic is intriguining in that it can be administred by IV or orally (pill). Valuation is about $300M

    Any new thoughts on MRTX?

    Thanks and keep up the good work!

    Dan

  33. ESPR – I am not aware of any new data for their lead program, so far everything is in line with plans. Perhaps people are worried about competition from PCSK9 antibodies, which a relevant concern but there is enough room for less effective oral drugs.

    ARRY – BTW, Genentech started p1 with another ARRY-invented compound
    http://clinicaltrials.gov/ct2/show/NCT01875705

    Dan – Sorry, not yet… too much work. Don’t have an opinion on TTPH but MRTX is interesting providing the new formulation leads to the desired exposure. Axl in general is becoming a hot target.

    Ohad

  34. Toby – Thanks for sharing, I wasn’t aware of this program although I am not sure if it made it to development or being pursued. In any case, this program can’t justify a 230M market cap in the absence of other value drivers (not sure about the their ITP program).

    Martin – Don’t know.

    ipollit – Nice find. Can’t really say what it means without a good PD marker that shows Axl inhibition. The problem with promiscuous drug like cabo is that it is hard to attribute activity to a given target. It is intetresting that the IC50 against Axl is similar to that against RET and we know cabo works well in patients with RET fusions, so who knows, EXEL may try this in Axl mutated tumors (quite rare). There is definitely an overlapping spectrum of activity between cabo and MRTX’s MGCD-265.

    Ohad

  35. Ohad, an amendment to RIGL: Per Sept. 30. they had stockholders equity of $ 223 Mio., they will end the year with $ 200 Mio. in cash. Rigel anticipates an additional $9 Million payments by the end of 2013 from AstraZeneca due to R256 (severe chronic asthma). The whole pipeline and the collaborations are only valued with $ 30Mio. In the past they had not much success, maybe better times are coming… Toby

  36. Toby/Ohad: RIGL Axl inhibitor is partnered with BerGenBio and that company now has the drug in Phase 1 I believe. I like that MRTX owns all rights to its Axl inhibitor (and other drugs) but no position just yet.

  37. Toby – I agree, any stock with such a low enterprise value bears close watching but bear in mind that without a meaningful catalyst this type of stocks can be traded below cash if market dynamics become less favorable.

    mcbio – Thanks, I wasn’t aware of this program at all. According to BergenBio’s site they completed p1 in healthy volunteers.

    Richard – Efficacy-wise, their clinical data is underwhelming imo as they don’t show responses in taxane pre-treated patients. The PK profile is encouraging though.

    Ohad

  38. I’m intrigued by Genmab’s Daratumumab but I couldn’t figure out how to purchase the stock. It is listed in NASDAQ OMX Copenhagen but the ADR GMXAY is too illiquid.

    I have an Interactive Brokers account that can trade stocks in NSYE Euronext but doesn’t include Genmab.

    How on earth did you buy Genmab in the States?

    Thanks for any reply and sorry for the non biotech question :-).

    Ohmson

  39. Bridgette – They showed intriguing signal but very preliminary. Waiting to see more data at ASH. In any case, their valuation is too high imo.

    Ohmson – Agree it’s an issue but I was able to buy some GMXAY a couple of months ago. I expect volumes to improve with the increase in visibility of dara (with the help of JNJ)

    Ohad

  40. Thanks for the reply. GMXAY is just too illiquid. For you and your readers’ info, I ended up buying some on Frankfurt exchange using IB (very decent transaction costs as well). Much better illiquidity. I do plan to buy the real deal using Fidelity although the transaction costs in about $30 flat. Daratumumab looks like a good bet!

  41. Can the cell therapy that is showing a very promising remission rate in both adult and children with advanced leukemia be a game changer in solid tumors like lung and breast.. Is this T cell gene therapy potentially a game changer for all cancers? Thanks.

  42. Scott- So far CARs demonstrated remarkable activity only in blood cancers. Still not enough data in solid tumors, especially with next-generation technologies.

    Ohad

  43. Infinity Press release:
    “…IPI-145 was highly active in patients with relapsed/refractory CLL, with a nodal response rate of 89 percent and an overall response rate of 48 percent…”

    Hi Ohad,
    that’s not good enough, right?

  44. In my opinion, no. So far activity in CLL does not seem differentiated from idelalisib except qucker onset of respose. One can always say that responses will get better with time but for now results look similar to me. The only positive sign was in PTCL (50% response rate), where ibrutinib and idelalisib are irrelevant but I want to see durability.

    Ohad

  45. Hi Ohad

    Have you seen the data Genmab presented at ASH and do you have some comments ?

    http://ir.genmab.com/events.cfm

    The Dara + Rev data looks very promising allthough its only a few patients – hopefully we will see better responses over time in the 8 and 16 mg dosing.

    I think the Ofa + Chl data looks very good – can you explain the big difference in IA data and IRC data ?

    Thanks

  46. Sukkeralf – Agree results were promising but small trial size with no control arm.
    IA – response and progrsesion is assessed by investigator, IRC – the person who assesses response and progression is independent and blinded (considered more reliable and conservative).

    Bridgette – They had a good data set with several responses across different B cell cancers. Durability in the press release looks somewhat short but perhaps higher doses will improve that.

    Ohad

  47. Any thoughts on the Array data presented? It seemed good, but the stock dropped about 13% yesterday. Puzzling.

  48. What did you think of Geron update. The data seems like it could be best in classin that it is hitting cancer in the bone marrow. Thank you.

  49. Mark – I actually thought ARRY’s data were in line to disappointing. ARRY520’s activity in myeloma is there but is not phenomenal and the combination p3 with Kyprolis is a long shot. The only game changer could be AAG as a biomarker.

    Scott – I thought GERN’s results were pretty good but still preliminary. Will take a better look when time permits.

    Ohad

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