ASCO 2015 preview

As in previous years, the upcoming ASCO meeting will be dominated by immuno-oncology with a particular focus on PD-1 antibodies. The market’s primary focus is expected to be on non-small cell lung cancer (NSCLC) with data from three large randomized trials from BMS (BMY) and Roche. Beyond lung cancer, investors will look for additional indications where PD-1 agents may have clinical utility as monotherapy or in combination with other agents.

Overall, PD-1 programs continue to generate positive data across many indications but to date clinical experience has been sobering. PD-1 antibodies may lead to durable responses in some cases but the vast majority of patients derive limited benefit or don’t respond at all. This is true in most indications with the exception of melanoma where PD-1 antibodies have a dramatic impact and combination with Yervoy appears to lead to further improvement. Below is a recap of some of the data which will be presented over the weekend. Abstract numbers and links are also provided.

PD-1 in NSCLC

Improvement in overall survival is starting to emerge with open questions regarding patient selection. It is already clear that while the survival advantage is clinically meaningful and will make PD-1 the standard of care, the magnitude of effect is limited with the vast majority of patients progressing within 1 year. One can only hope that in some patients PD-1 antibodies will generate durable responses and potentially cures.

In pre-treated unselected patients, the three leading PD-1 inhibitors generate a ~20% response rate. Response rate improves to up to ~40% in patients with high PD-L1 expression (exact Dx tool and threshold varies) whereas PD-L1 negative/low patients have a 10-15% response rate. Importantly, PD-L1+ patients represented 20%-70% of patients depending on cutoff and diagnostic kit.

BMS will present two P3 studies evaluating Opdivo in squamous and non-squamous patients, respectively. Data from the squamous trial (CheckMate 017, #8009) have already been published and demonstrate a 3.2 month (9.2 vs. 6 months) survival benefit, which is clinically meaningful but not dramatic. Response rate was also superior (20% vs. 9%). Interestingly, there was little to no difference in survival based on PD-L1 expression using multiple cutoffs. Results from the non-squamous study will be published at the meeting (#LBA109) and are expected to be positive as well.

Roche will present data from a randomized P2 (POPLAR, #8010), which evaluated MPDL3280A (anti-PDL1) vs. chemo in previously treated patients. In the entire patient population, the antibody demonstrated a similar response rate (15% vs. 15%), a slightly inferior PFS (2.8 vs. 3.4 months) and a modest 2-month survival benefit (11.4 vs. 9.5). In contrast to Opdivo’s data MPDL3280A’s effect was more pronounced in patients with PD-L1 expression with a clear correlation between survival benefit and level of expression (hazard ratio of 0.47 in tumors with the highest expression level). Patients with PD-L1 negative tumors (32% of patients) derived no benefit from MPDL3280A.

It is still unclear whether the difference between BMS’ and Roche’s data sets stems from inherent differences in the antibodies or patient selection tools. BMS’ Opdivo targets PD-1 and blocks interaction with both PD-L1 and PD-L2 whereas Roche’s MPDL3280A binds only PD-L1, which may explain the stronger correlation with PD-L1 expression. Based on the data available to date with all PD-1 antibodies, I tend to ascribe at least some of the discrepancy to biomarkers, which widely vary among the different programs. In the short run, BMS has a clear lead over Roche and Merck (MRK) as Opdivo will likely be used regardless of PD-L1 status. However, Roche’s ability to stratify patients based on sensitivity to PD-1 agents (needs to be validated in additional studies and indications) may become an important tool in developing combination regimens. For example, Roche may be able to pursue PD-L1 negative tumors as a fast and cheap route to market for new immuno-oncology combinations.

Moving to 1st line does not seem to dramatically improve results based on abstracts for Keytruda (#8026) and Opdivo (#8025). For Keytruda response rate in the overall population (all had some PD-L1 expression) was 24% and PFS was 6 months, which is comparable to standard of care treatment. For Opdivo, response rate was 21% in the overall population. Abstract for Roche’s MPDL3280A reports a 29% response rate in first line patients (#8028). Preliminary findings in all abstracts point to a correlation between PD-L1 levels and clinical benefit but numbers are small and data are immature.

Roche will present combination results of MPDL3280A with various chemotherapies in 1st line patients (#8030). The abstract discloses an encouraging response rate of 67%, which is higher than what would be expected with MPDL3280A or chemotherapy alone (25-30%). When added to chemotherapy in the same setting, Opdivo generated a ~40% response rate last year at ASCO 2014 but it is unclear whether there is a real difference.

This year’s meeting will have data for PD-1 antibodies with CTLA-4 antibodies, which are likely to keep the debate regarding this strategy in lung cancer alive. As a reminder, at last year’s meeting BMS presented disappointing results for Opdivo + Yervoy in NSCLC. Response rate was 20% and the addition of Yervoy led to significant toxicities. This year Merck and AstraZeneca will present preliminary findings from their combination studies, respectively. Merck’s abstract (#8011) for Keytruda+Yervoy includes a high response rate (55%) but the sample size is very small (11 patients). AstraZeneca’s abstract for MEDI4736 + tremelimumab demonstrates a lower response rate (26%) in 31 patients (#3014).

PD-1 in other indications

Beyond NSCLC, companies will present data in multiple indications, most of which have already been shown to be relevant for PD-1. Activity is observed across all programs with clear signs of a correlation between PD-L1 expression and clinical benefit. Similarly to the case in NSCLC, most patients do not appear to derive meaningful clinical benefit as response rates in the general population are 20% or lower. In some cases, patient selection results in a higher response rate but so far durability of response and impact on long term survival remain limited.

Melanoma – With both Opdivo and Keytruda approved for melanoma, focus is shifting to combinations. BMS will present results from a P3 data evaluating Opdivo + Yervoy vs. each agent alone (#LBA1). As a late-breaking abstract, no information is disclosed prior to the meeting but expectations for the combination arm are high. BMS will also report a P2 trial evaluating the combination vs. Yervoy alone (#9004). The information in the abstract reveals a dramatically better response rate (60% vs. 11%) and PFS (8.9 vs. 4.7 months). Based on cross trial comparisons, these response rates are numerically superior to the ~35% typically seen with PD-1 antibodies alone.

Renal cancer – BMS will present updated survival data with single agent Opdivo (#4553). Results continue to demonstrate promising survival at the two higher doses as reported at last year’s meeting (although response rates and PFS were underwhelming). This year’s abstract includes analysis based on PD-L1 status which demonstrates a dramatic difference of almost 1 year (29.9 vs. 18.2 months) in favor of PD-L1+ patients. This bodes well for PD-1 antibodies in renal cancer but the promising survival signal should be interpreted with caution in the absence of randomized data. Merck will report combination data for Keytruda+Yervoy (#3009). The abstract does not include efficacy data, which will be presented at the meeting.

Bladder cancer – Bladder cancer is one of the few indications where Roche has a clear lead over BMS and Merck, based on very strong results for MPDL3280A in PD-L1+ patients. This year, Roche is presenting updated data (#4501) which continue to demonstrate an impressive response rate in PD-L1+ vs. a modest response rate in PD-L1- patients (46% vs. 16%). At the meeting, it will be interesting to see updated response durability and PFS, which are immature in the abstract. Merck will report results for Keytruda, which also demonstrate a higher response rate in PD-L1+ patients (38%) (#4502).

Small cell lung cancer – BMS will present data for Opdivo and Opdivo+Yervoy in patients regardless of PD-L1 status (#7503). Response rate in the combination arm (25%) appears better than that observed with Opdivo alone (15%). Merck will present data for Keytruda in PD-L1+ patients (#7502), which demonstrated a 25% response rate according to the abstract.

Ovarian cancer – Merck and Merck Serono/Pfizer will report initial data for Keytruda and avelumab, respectively. Response rate was modest (11-14%) even in PD-L1+ patients. (#5510)

Esophageal cancer – Merck’s Keytruda demonstrated a  23% response rate in PD-L1+ patients according to the abstract (#4010).

Gastric cancer – Merck will report updated results from KEYNOTE-012 in PD-L1+ patients (#4001). The abstract discloses a 22% and 33% response rate by central and investigator review, respectively. 6-month PFS and OS were low (24% and 69%, respectively). Merck Serono/Pfizer’s avelumab will have data from a Japanese study. The abstract reports responses in 27% (3/11) of patients. (#4047).

At the meeting, data are expected for Opdivo+Yervoy in glioblastoma (#3010) as well as two late breakers for Keytruda in colorectal and head and neck cancer.

Immuno-oncology beyond PD-1

In parallel to the unprecedented resources allocated to PD-1 programs, there is an industry-wide effort to find the “next PD-1” or agents that can augment PD-1 inhibitors. These include new immune checkpoint targets (LAG-3, TIM-3, VISTA, KIR etc.), co-stimulatory agents (OX40, CD27, CD40, 41-BB etc.) and other agents designed to stimulate the immune system (IDO, CSF1R, vaccines). In most cases, new programs are pursued in combination with PD-1 antibodies.

Recent deals for novel immuno-oncology assets exemplify their tremendous value in today’s industry even at an early stage. AstraZeneca’s deal with Innate Pharma (IPH.PA) for IPH2201 included a $250M upfront payment, which is quite high for an antibody that has phase I data in healthy volunteers. Earlier this year, BMS paid $800M for Flexus and its preclinical IDO inhibitor. IDO is one of the hottest targets in immuno-oncology but Flexus’ IDO program is years behind Incyte’s (INCY) IDO inhibitor and at least one year behind Newlink’s (NLNK) IDO program (partnered with Roche). Aduro (ADRO) landed another massive preclinical deal for its STING agonists with Novartis (NVS) which agreed to pay $200M upfront (plus $50M in equity investment).

This year’s ASCO includes very few new immuno-oncology programs and limited combination data (most combination studies were only recently initiated).The elephant in the room this year is Incyte’s IDO inhibitor, which demonstrated intriguing efficacy in melanoma last year. IDO is one of the hottest targets in immuno-oncology, evidenced by recent deals around the target. Incyte’s program is in combination studies with three different PD-1 inhibitors which started last year. Data from these trials is expected in 2016.

Cancer vaccines – On the cancer vaccines front, Amgen (AMGN) and Celldex (CLDX) will present updated results for their programs in melanoma and GBM, respectively. Amgen’s T-VEC will have long term follow up for T-VEC+Yervoy. At last year’s meeting, investigators presented a dramatic response rate (56% including 33% CR) compared to ~15% typically seen with Yervoy monotherapy. This year’s abstract does not include additional patients, but results continue to impress with a PFS of 10.6 months (#9063). Celldex will report updated survival data for its EGFRvIII vaccine (rindopepimut) in GBM (#2009). If the survival benefit reported in November is corroborated, the trial may be sufficient for accelerated approval.

Antibodies – Results for new targets will be presented for Roche’s CSF1R antibody (#3005), which is designed to inhibit tumor-promoting macrophages, and Immune Pharma’s/BMS’ anti-KIR antibody (#3065), designed to activate NK cells. Both agents demonstrated little to no efficacy. Pfizer will present data for 4-1BB in combination with Rituxan in non-Hodgkin’s lymphoma (NHL). Results in the abstract include a modest response rate (22%) that can be attributed to Rituxan to some extent but there were 2 intriguing long term CRs in a subset of NHL (#3004).

Other agents – Additional intriguing programs include ARMO’s pegylated IL-10 (#3017), which demonstrated signs of efficacy in renal cancer and ocular melanoma (a tumor type resistant to PD-1) and Roche’s CEA-IL2v, which comprised of an engineered IL-2 fused to CEA to enable better targeting of IL-2 into tumors (#3016).

Next year, investors can expect a flood of clinical data with new immuno-oncology agents. The most promising targets are OX40 (Pursued by AstraZeneca, Roche and Pfizer) and IDO.

Stock related news flow (non immuno-oncology)

ASCO will have important data for some of the companies I follow. Although these are not immuno-oncology programs, they represent significant advances as well as important value drivers.

Clovis Oncology – Clovis (CLVS) will report updated results for rociletinib in EGFR-mutated NSCLC (#8001). Response rate in T790M+ patients was 48-49%, which is lower than previous updates (67%). PFS is not reported in the abstract (was 10.4 months at the last update) and is expected to be a key focus given the neck and neck race with AstraZeneca’s AZD9291. Results will be compared to AZD9291’s recent data update, which included a response rate and PFS of 54% and 13.5 months, respectively.

AZD9291 appears numerically superior based on cross-trial comparisons but this difference may stem from imbalances in patient characteristics, especially geographical distribution. In the AZD9291 study, 61% of patients were Asian whereas the majority of patients in the rociletinib trial were non-Asian. Asian patients are known to derive more benefit from 1st-gen EGFR inhibitors like Tarceva and Iressa but it is not clear whether this is the case with next-gen EGFR inhibitors.

Preliminary data from Astellas’ ASP8273 imply that Asian patients are indeed more sensitive to next-gen EGFR. Astellas is presenting two phase I trials with ASP8273 in the US and Japan respectively. The abstract for the Japanese study (#8014) reports an 80% response rate whereas in the US study the same drug achieved a 25% response rate (#8083). If the difference holds when updated results are presented, comparing rociletinib and AZD9291 will become even more challenging based on available data.

Clovis will also report updated data in T790M- patients, where rociletinib continues to demonstrate a surprisingly high response rate (33%-36%). This is emerging as another differentiator from AZD9291, which reported a 21% response rate with short durability. Rociltenibs’ activity in T790M opens up a new significant commercial opportunity and more importantly, bodes well for the ongoing study in 1st line patients, where most patients are defined as T790M-.

Immunogen – Immunogen (IMGN) will report highly anticipated results with IMGN853 in FR+ ovarian cancer (#5518). Following the monetization of Kadcyla’s royalties, IMGN853 remains Immunogen’s primary value driver in 2015, which makes the data at ASCO extremely important for the stock. Preliminary data in the abstract are aligned with expectations set by management (discussed here) with a 40% response rate but the small sample size (10 patients) and limited follow up  make it difficult to interpret the data. A new dosing regimen appears to mitigate ocular toxicities, which had been viewed by the market as a major issue in the past. At the meeting, investors’ focus will be on updated response rate in additional patients and response durability. A >30% response rate may enable Immunogen to pursue this indication with a single arm study based response rate.

Genmab – Genmab’s (GEN.CO) partner, J&J (JNJ) will present P2 data in heavily pre-treated multiple myeloma patients (#LBA8512). Although abstract details are embargoed, top line results have already been announced with a 29% response rate and a 7.4 month durability of response. This study will serve as the basis of an accelerated approval filing later this year.

Interestingly, response rates observed to date with daratumumab may underestimate its true anti-tumor effect based on an abstract from J&J (#8590). As disease activity is measured by antibodies secreted by myeloma cells in the blood, daratumumab may be identified as a sign of disease activity. Genmab’s management already disclosed that distinguishing between daratumumab and myeloma protein leads to increases in CR rate but this is expected to gain more visibility only at ASH.

Genmab will also present initial data for TF-ADC, developed in collaboration with Seattle Genetics (SGEN). The abstract discloses an ongoing response in a patient with cervical cancer (#2570).

Foundation Medicine – Foundation Medicine (FMI) and collaborators will present a large body of clinical work which demonstrates the utility of the company’s tumor profiling technology. This year, results include validation of new MET mutations as biomarker for MET inhibitors (#11007), identification of ovarian cancer tumors that are sensitive to PARP inhibitors (#5508) and identification of actionable mutations in certain rare tumors. The most intriguing abstract is for a prospective study comparing patients who received biomarker-matched treatment to those receiving non-matched therapy (#11019). The abstract reports a statistically significant survival difference benefit for patients receiving matched therapy, which is the first large prospective study correlating FoundationOne and clinical outcome. With shares under pressure after a weak quarter and reimbursement concerns, it is up to Foundation Medicine to continue to demonstrate the utility of its tumor profiling system.

ArQule – ArQule (ARQL) will report updated data for its FGFR inhibitor, ARQ087 (#2545). The abstract describes two previously disclosed cases of cholangiocarcinoma patients  with FGFR2 fusions who achieved a PR (maintained for ~5 months) and a durable minor response (ongoing). ArQule recently initiated a P2 in this patient subgroup but it is unclear whether additional patients will be included in the data set at ASCO. FGFR2+ cholangiocarcinoma represents a modest commercial opportunity (hundreds of patients in the US annually) but given the high unmet need the regulatory route will be very favorable.

111 thoughts on “ASCO 2015 preview

  1. Hi Ohad,

    Any thoughts on HER2 inhibitors Neratinib and ONT380?

    Thanks.

    Rick

  2. Rick (PBYI/ONTY) – I don’t have a concrete opinion on PBYI, despite the lower than expected absolute benefit, the drug clearly works but with the current price tag that’s a tough decision.
    Re: ONT380, so far results did not generate a promising signal in combination with Kadcyla or chemo. Initial signs in brain mets is intriguing but early.

    Ohad

  3. For PD-1 checkpoint inhibitors, there’s also a first peek at HCC results:

    “Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040.”

    This is an indication with unmet need, and I didn’t see anything from the preliminary multiple indication Phase 1 trial: “Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: Survival and long-term safety in a phase I trial” so I figured it didn’t work, but perhaps it just wasn’t included in that cohort?

    Also IMGN853 has a second dose in trial with adjustment to ideal body weight and dosing on three weeks out of every four which is reporting a much better clinical benefit proportion but worse toxicity in an array of different folate receptor expressing tumors:

    “http://abstracts.asco.org/156/AbstView_156_150531.html”

    The recommended P2 dose is still being determined but it shows promise beyond EOC in endometrial cancer and NSCLC.

  4. Wildbiftek – Having any efficacy in HCC should be meaningful given the lack of treatment alternatives.
    Re: IMGN853, the more dose intensive regimen appears more toxic based on the abstract but it’s hard to assess with the limited data disclosed in the abstract. Based on the correlation between Cmax and ocular toxicities, using weekly administration (or every 2 weeks) may be advantageous.

    IMGN is working with NCCN on expanding program beyond gyn. malignnacies:

    http://www.nccn.org/about/news/newsinfo.aspx?NewsID=507

    Ohad

    Ohad

  5. Will we receive any updates from MRNS and ARRY ? Do you see anything interesting from these 2 ?

  6. ruhulla –

    MRNS – The company will provide updates from two orphan indications (FXS and PCDH19) later this year. Expectations are low so I don’t see a lot of risk. An update regarding the IV formulation for acute settings can also be an important catalyst.

    ARRY – Not a lot of data at ASCO but later this year they’ll have results from P3 NRAS+ melanoma.

    Ohad

  7. Hey Ohad,

    With regards to Clovis you didn’t mention ARIEL trials. seems to me they have some pretty strong activity in BRCA like tumors. No?

    I was also at AACR and I saw lot of posters that compared AZD9291 to rociletinib in pre clinical settings w.r.t o resistance. seems like AXD9291 was more specific, potent and atleast in pre clinical setting it took a lot more time for cells and tumors to develop resistance. Makes sense to me that rolectinib is showing some activity in T790M- patients but then it also means AZD9291 will be superior in T790M+ patient.

    What do you think?

    Thanks as always.

  8. Noteable absence of Exelixis in your prewiev although they
    present 14 papers.
    Are you signaling by this your reservations towards this Co. ?

  9. Amol (CLVS) – Agree about ARIEL2, this is an important differentiator. Also a good testament for FMI’s platform.
    Don’t know about preclinical data that demonstrates superiority of one compound over the other. In the clinic both drugs look good and judging by Astellas data rociletinib is being evaluated in a more challenging patient population. I don’t think T790M- activity implies something about the drug’s activity in T790M+.

    rodolfo (EXEL) – Actually, there were some interesting abstracts. The randomized trial vs. Tarceva was clearly positive (although safety is still an issue). The RET+ NSCLC was somewhat disappointing (I was hoping for a 50%+ response rate), looks like there are more potent and selective RET inhibitors from Roche BPMC.

    Ohad

  10. Thanks Ohad. Clovis is really on cusp of something great with two drugs both getting BT designation. Thanks for your original post although I made my buys much later.

    Abt EXEL makes sense given the sell off after ASCO abstract release. TKIs are always toxic so I am no surprised y the toxicity at 60mgs. What is your take on Cabo in RCC given that it had similar data w.r.t to PD-1/PD-L1? I think combination will even work better.

  11. Hi Ohad,

    Any thougts on Affimed (AFMD), they will present some programmes on ASCO.

  12. Amol – Although I am long CLVS it’s important to acknowledge that risk is still high as good news are already factored in and expectations are high.

    Re EXEL – It will be hard to combine cabo with PD-1 based on experience with Sutent/Votrient. However, if the RCC trial is successful, cabo will become a meaningful treatment option.

    Bert (AFMD) – The CD33 program is promising but early. I still have doubts regarding the CD30/CD16 program as a viable treatment option.

    vnmaster – Of these names my favorite is LOXO, they have a winning approach and potential for clinical proof of concept this year in Trk+ tumors. I like the ARRY collaboration and focus on highly selective kinase inhibitors. CALA is very interesting but so far activity is limited. AVEO and VBLT are not attractive imo.

    Ohad

  13. Hello Ohad
    how come Inst. own just 1% in OCAT , is it too early for them?
    what do you think about STEM?

    how GLPG can affect on INCY?

    Thanks
    Alex

  14. Alex – Don’t know regarding OCAT. Don’t know STEM well, just got Cantor’s initiation report on them and I plan to go over it.

    GLPG’s selective JAK1 inhibitor can become the preferred JAK treatment in RA assuming a better safety profile. I don’t think the market ascribes a lot of value to baricitinib so I wouldn’t expect anything dramatic. Investors’ focus is on IDO and Jak inhibitors for solid tumors.

    Ohad

  15. Hello Ohad, Can you please give your thoughts on ONTY, LBIO, BPMC, LIFE? Thanks bud.

  16. Ohad
    Do you have an opinion about CSF1R antibody of FPRX?
    Some analysts (Oppenheimer) believe that it is the best in class for treatment of cancer, rare diseases and inflammatory disorders. They expect data in YE15 for ultra-rare PVNS disorder, followed by a pivotal / registration trail and fast path to approval. Also in RA they have very good safety profile with only 1-2 AEs which could be a differentiator. Plus 6 trails in combo with PD-1 collaboration with BMS, collaboration with GSK and as of yesterday – with BLUE..

  17. I just saw a note from BMO discussing FPRX FGFR2b antibody. They believe that their approach to develop companion diagnostics can give them an edge in gastric cancer vs AZN pan-FGFR inhibitor. Any thoughts?

  18. vnmaster –
    ONTY – So far clinical data is not overwhelming given the fact ONT380 is combined with active agents. Brain mets activity can be a wild card but for now ARRY provides some exposure to the drug.
    LBIO – TILs work but the logistics are challenging. No concrete opinion there.
    BPMC – Great approach and high quality assets but too expensive for a pre-clinical compny.
    LIFE – Phenomenal science but I prefer to wait for a better entry point.

    andre – CSF1R is an attractive target but so far activity has been observed only in PVNS, where Roche and Daiichi have a clear lead. On paper FPRX’s antibody is differentiated because it competes both ligands and does not block dimerization (in contrast to Roche’s antibody). It is hard to speculate whether this will lead to a distinguished clinical profile. Combination with PD-1 is a good approach but it will take time for data to emerge and there is no guarantee for success.
    Re the FGFR2b antibody, so far small molecules proved to be more effective than antibodies especially in FGFR fusions. FPA144 has good preclinical results but so far solid tumors proved to be a tough nut to crack even for ADCC-enhanced antibodies. Bottom line, a very high risk program imo.

    vnmaster (TCON) – Not a big fan, clinical data to date have been underwhelming imo.

    Ohad

  19. Hi Ohad,
    Great site btw. Was wondering if you had any thoughts or know anything about TNXP.

    Thanks,
    Al

  20. interested to know your thoughts on cldx for Monday ohad? a 5m os would be awesome. No play but thinking. Thank you

  21. Hey Ohad
    thanks for sharing your views prior to the meeting!

    I wonder if you had a look at the top-line STML press release. Any thoughts? Lacks detail, but sounded good to me (no toxicities and with high response rates, including CRs.

    regarding VBLT, it seems the market and some analysts are excited about the data they will be releasing at ASCO, why are you unimpressed? I had bought a few hundred shares when it was in the $3 and I am wondering what to do.

    Any additional thoughts on CTIC? besides their management not being very upfront…

    Thanks

    Dan

  22. Hi Ohad,

    Thanks for the preview.

    I’m eagerly anticipating the IMGN853 results. Expect them to present data on more than 10 pts after speaking with the management.

    Do you ascribe any value to other clinical assets e.g. SAR3419 (returned from Sanofi) and IMGN901 which has just been re-entered trials for leukemia and childhood cancers. https://clinicaltrials.gov/ct2/show/study/NCT02420873

    Thanks
    James

  23. Al – Thanks. Sorry, not following TNXP.

    Stephan (TBIO) – Not a big expert in Dx but teh field of liquid biopsies is certainly gaining momentum. Not sure that TBIO’s focus on PCR is a positive given the shift to NGS.

    Mike (CLDX) – I am keeping my fingers crossed, this could be a huge win for patients and cancer vaccines in general. Nevertheless, it’s important to note GBM isa notoriously difficult indication and corroborating OS signals has been challenging so there is considerable risk that results on Monday will be disappointing.

    Dan (STML) – The PR was limited in details but should certainly be viewed as positive as it validates initial signs of efficacy in an earlier trial. The tolerability profile looks relative ok, the only missing piece of info is durability of response , which is crucial for getting approval with this study.

    James (IMGN) – Thanks, so am I ;). I don’t ascribe any value to these programs, only to the CD38 antibody now that CELG is out of the race. Ideally, SNY should give back that program back if it decides to shut down oncology.

    Ohad

  24. Ohad
    CTIC has good data on ASCO – 23% response in pts with low platelets, plus 26% become transfusion independent, compared to zero for both accounts in control arm.
    Do you think the current valuation is reasonable, considering that they will apply for NDA by the end of the year.

  25. Hey Andre
    I am long CTIC since preliminary results, when the stock shot to $2.25. Added a little more on the dips, yesterday too, on expectation of solid ASCO results. I hope that on monday the valuation will go higher.
    Dan

  26. Dan,
    looks really good – Phase II single agent rucaparib update – 74% ORR

  27. Hi Ohad,

    Immunogen just updated their data to show a 53% ORR in Ovarian cancer for IMGN853 in FR positive patients. They announced a P2 trial for late 2015 that could be used for registration.

    My understanding is that FRα-positive ovarian cancer is far more common than the BRCA-positive type (~90% vs 10-20%) so this is a much bigger indication for IMGN than Rocelitinib’s is for CLVS.

    With the failure of Vintafolide and Farletuzumab, IMGN853 looks like it could be the key treatment in this space. You talked about Vintafolide before, but what is your opinion of IMGN853 in light of the failure of Farletuzumab’s P3 trial in combination w/ taxanes and platinium despite good ORR in earlier stage trials?

  28. Hey Wildbiftek
    Great for IMNG.
    re CLVS, their drug, the case they are making with the ARIEL trials, is that the drug works for 60% not just 15%
    Dan

  29. Hi Dan,

    I mean Rucaparib in my post. The sub-indications for IMGN853 and Rucaparib are different (FRα-positive BRCA-positive) and and I was comparing the relative size of each. According to this site:

    http://www.mycancergenome.org/content/disease/ovarian-cancer/

    The prevalence of BRCA1/2 mutations in high-grade ovarian cancer is 10-20%.

    For FRα:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707764/

    indicates a prevalence of 72% for primary site ovarian tumors whereas:

    http://www.researchgate.net/post/Is_targeting_folate_receptors_using_folic_acid_really_useful_in_the_treatment_of_cancer

    claims a prevalence of > 90%.

    The ORR of Rucaparib in its sub-indication is great but the sub-indication of Mirvetuximab Soravtansine is much larger.

  30. Wildbiftek
    According to CLVS, BRCA-like ovarian cancer represents 42% of ovarian cancer patients, 25% – BRCA mutations and only 33% the rest (bio-marker negative).
    From the reported data they have 80% ORR in BRCA-2; 72% ORR in BRCA-1 and 74% in all gBRCA mutations. Not sure if “all” covers BRCA-like

  31. The studies are also different in that the IMGN853 patients are probably platinum-refractory by study design whereas Rucaparib ARIEL-2 patients were platinum-sensitive. This is probably why the IMGN853 news from today indicated that a subsequent P2 trial would be sufficient for registration, and that they were exploring combos for earlier stage ovarian cancer.

  32. andre (CTIC) – I am cautious as the 23% is from a small subset (35 patients) of patients with low platelet count and in the general population the drug looks inferior to Jakafi (cross trial comparison). The track record of CTIC’s management is so bad that I wouldn’t invest in it anyway.

    CLVS vs. IMGN (Dan/Andre/Wildbiftek) – Both data sets look solid and although there might be a lot of overlap in patient populations eventually, both may become important ovarian cancer drugs. CLVS’s response rate and PFS data are impressive but it’s too early to proclaim rucaparib a best in class PARP inhibitor due to the different patient population (olaparib’s P2 in grBRCA+ was in more heavily pre-treated patients and generated a 34% response rate).

    IMGN’s surprisingly high response rate of 53% is in a smaller sample size (17 patients) but the main advantage here is the complete lack of competition (I don’t view ECYT as a real competitor). The market is wide open for anti anti-FRa agent if P2 corroborates this activity.

    Ohad

  33. Hey Ohad,

    Clovis just announced their results on roli. Reading your write upakes me think they had better ORR 60%than what you thought . the median pfs was 10.3 month same as last year.
    Given their breakdown wrt to CNS metastasis patients what is your take? And still encouraging activity in mutation neg patient 37%.

    Thanks

  34. ohad

    if you had to pick three small cap(100m-1b)three mid cap(1b-5b) and three large cap biotech stocks to outperform the sector over the next 12 months which would they be?

  35. Hi Ohad

    Are you following Neostem (NBS)? They are developing an immunotherapy which uses a patient’s own tumor cells and their lead candidate, NBS20, showed strong data in a Phase 2.

    Many thanks

  36. amol (CLVS) – Overall results are disappointing although I still think rociletinib is at least as good as AZD9291. The 8-month PFS for all comers is lower than expected and while this can be explained by geographic and brain met imbalances, it needs to be validated in future trials. The response rate in T790M- continues to look good.
    Bottom line, I expect the stock to take a hit today (~15%) although long term there is still a high likelihood of rociletinib to be the market leader.
    ASP8273’s data today (Monday) will be important validating the better activity in Asians hypothesis…

    dave – I think the portfolio above represents a diverse collection of small/mid cap biotech stocks. New small caps I am tracking are : LOXO, TRVN, XENE, AUPH but I still don’t have a position there.

    Kevin (NBS) – Sorry, don’t know them well.

    Ohad

  37. Hey Ohad
    Re CLVS – disappointing compared to expectations? Or to AZN results? What do you think the implications are, regarding other treatment options for that population including immuno-modulating drugs, and market for rocitelinib?
    Any thing that caught your eye at ASCO so far?
    Thanks a lot!
    Dan

  38. Yes, he has a one line link at the bottom…. Saying it was originally posted on your blog, but looks fishy to me

  39. HI Ohad
    what do you think on the EXEL news?
    didnt they supposed to publish data from rcc?
    thanks

  40. Dan (CLVS) – I expected 10 months in the overall population, hence my disappointment. Don’t think there are meaningful implications as I still think rociletinib is well positioned for T790M+ and may be superior to AZD9291 at least in T790M-neg patients.
    I don’t view immunomodulating agents as competitors as the vast majority of patients need other options, plus, 3rd gen EGFR inhibitors have a fantastic efficacy. I don’t see how a T790M patient will not receive rociletinib or AZD9291.
    So far, i did not see a lot of surprises. IMGN853 was a positive surprise and rucaparib’s data were also quite impressive. I feel that I may have underestimated its value.

    Thanks for the link, I asked them to remove it.

    Ohad

  41. Alex (EXEL) – The overall survival data in the cabo+Tarceva trial were surprisingly positive. The RET+ study is somewhat underwhelming, more selective RET inhibitors may do a better job in that setting.

    RCC data should come any day now, was not supposed to be at ASCO.

    Ohad

  42. hi Ohad

    Argen-X with a nice run the last days and especially today with +20% currently. there was some data at ASCO on ARGX111 which I did not find so impressive (with my limited knowledge). What do you think?

    ONTY probably with a great day today after ASCO update – it seems that ARRY could have given away one of their very best assets, don’t you think?

    thanks!
    Christian

  43. The latest post abstract data is showing better ORR numbers than the abstract did:

    https://twitter.com/Latinamd/status/605032284589305856

    44% PR (38% confirmed) is nothing to sneeze at, but might be just short of what’s needed to run a quick registrational trial. We’ll see how ponatinib does here but there’s a major toxicity trade-off with that drug.

  44. Hi Ohad,

    There seems to be general sentiment in the media that CLVS missed at ASCO, but I am not sure I exactly understand the interpretation. Maybe in the near term, but it looks like have two very legit molecules that seem to be likely to be approved and have market success. In particular, the side effects for Rociletinib may differentiate itself and the fact that it could actually be a better molecule than AZD9291 though I appreciate this is known with the current data to date.

    It just seems to me that CLVS became an even more likely takeover candidate by someone like Pfizer or Roche…do you agree?

  45. Christian
    ARGX – Their approach of creating an enhanced anti-MET antibody with multiple modes of actions makes sense but so far clinical results are limited and does not include a meaningful efficacy signal.

    ONTY – I think their data is very hard to interpret with all different combination regimens. If anything, it looks like Xeloda contributes a significant portion of the efficacy. The brain met activity is intriguing, no doubt and could be a differentiator going forward. The HER2 landscape is a tough one to navigate but since Kadcyla will probably not make it to 1st line, they have a good compbination partner for last line patients.

    Wildbiftek (EXEL) – Efficacy is there no doubt and imo this is sufficient for accelerated approval. What worries me is more selective RET inhibitors such as Roche’s alectinib which have a high likelihood of being superior in this setting.

    Elyas (CLVS) – I agree that CLVS has two approvable drugs with attractive clinical profiles and blockbuster potential. Rociletinib’s safety profile looks better than that of AZD9291 but the safety aspect becomes secondary if efficacy is not comparable. Hard to predict M&A activities but if I were a pharma company looking for new oncology drugs, CLVS would be the first place I would go to.

    Ohad

  46. Ohad, big big BIG thanks on IMGN. Seemed like a decent bet on ovarian results after reading your summary and comments so I purchased $10 calls at 15 cents. 3000% is the second biggest gain I ever made :)

  47. JQ (RXDX) – Agree, 3 out 3 means Trk fusions represent a new subset and that RXDX’s drug is active. However, given the short response duration of thefirst response (CRC) more follow is needed to see this is clinically meaningful. Down the road, I would bet on LOXO’s selective inhibitor in this patient population rather than on RXDX’s promiscuous drug.

    Dan (IMGN) – Thanks, very strong market reaction glad they are back on the horse.

    Usubanas (IMGN) – Thanks and glad you made a profit.

    Ohad

  48. Hi Ohad, did you hear anything interesting about T-DM1 today from ASCO?

    I was wondering what happened in MARIANNE, that despite much superior DoR, PFS was not stat-sig better for the T-DM1 arms. I’m guessing response rate must have been worse. It looks like it has a better safety profile than T + Taxanes so it’d be a better candidate for combos.

    Results were also presented for ADAPT for pre-op HER2+ ER+ breast cancer with T-DM1 vs T, pCR reponses were far better:

    https://twitter.com/BMTJolene/status/605390266455982082

    There’s also quite a few other breast cancer trials in store for T-DM1:

    https://twitter.com/fgunico/status/605371611752112128

    Although $IMGN hedged some time to market risk, I’m still curious about T-DM1’s ultimate time to market.

  49. Ryan (FMI) – ASCO was a good meeting for FMI both directly and indirectly. The “basket trial” which demonstrated improved survival with precision medicine. This is a good indication but such studies should always be interpreted with caution due to many confounding factors.
    CLVS’ rucaparib data was very important as it may become FMI’s first opportunity to have an approved companion Dx product. Same goes for AGIO’s IDH drugs, which did not have an update at ASCO.

    steve (HALO) – Thanks. Good signal but numbers are too small imo. I am sitting this one out for now.

    Ohad

  50. Wildbiftek (IMGN) – I think it will be hard to compete with Perjeta+Herceptin 1st line despite T-DM1’s favorable safety profile. The most important study for T-DM1 this year is in gastric cancer.

    Alex – Re INFI, nothing surprising good or bad, looks in line with other isoform-selective PI3K inhibitors.
    Re EXEL – negative results would crash the stock imo but like you I am cautiously optimistic.

    Angelina (FGEN) – Still don’t have a concrete opinion. Both of their programs are of good quality, no doubt, not sure about valuation.

    Ohad

  51. Heard anything about Sanofi turning to IMGN to conjugate SAR650984 in order to distinguish it from Daratumumab? The results have looked similar for those 2 so far in MM.

  52. Hello Ohad,
    congratulations for your summary on ASCO stocks. Some of your targets perforemd really well. I have a question about ESPR. I know you have it in your portfolio for long time ago. Are you still optimistic? It has retracted recently to $99. I am considering to start a position but will like to hear your view. Thanks in advance

  53. Ohad

    will AZD break down their data in terms of patient population?isn’t it possible that the us/european patient data could be very similar in terms of PFS when comparing the AZD and CLVS lung drug.

  54. Hi Ohad
    why STML didnt provide durability of response ? what could be the reasons?
    is there any catalyst for them in the coming 6 month?
    Thanks
    Alex

  55. Hi Ohad

    What is your take on the recent quite substential (automated…) insider sellings at AAVL? Any kind of red flag?

    Many thanks

  56. Wildbiftek (IMGN) – I am not aware of such attempts. CD38 is broadly expressed on a lot of tissues so conjugating it may have a narrow therapeutic window. Some companies are developing CD38XCD3 bispecific antibodies but toxicity is a major concern there as well.

    lgonber (ESPR) – Thanks. Yes I am still optimistic with multiple upcoming catalysts (hypertension study, P3 start) and a potential takeover. Bottom line, they have an LDL-lowering oral drug with new MOA and potential benefits beyond LDL and a good safety profile (so far).

    Wildbiftek (IMGN) – BT-062 has limited activity as monotherapy which makes me less excited about it but the combination data are strong and elotuzumab showed that even drugs that are no effective on their own may have value in combination (albeit more limited). I am eager to see BT-062’s data in solid tumors, the trial is enrolling patients for over a year now.

    dave (CLVS) – I haven’t seen such breakdown and I am not sure AZN will provide it. The fact they haven’t leads me to suspect activity is better in Asian patients because this could be the best way to refute CLVS’ claims.

    Alex (STML) – The press release was very limited in details, hard to speculate whether they excluded durability because it was unfavorable or they would like to reserve data to ASH in December (which is the primary catalyst this year).

    Kevin (AAVL) – I always prefer to see acquisitions but it is hard for me to interpret these sales. We will know whether they were right in the coming weeks…

    Ohad

  57. CLVS:

    Hello Ohad,

    i wonder, which commercial potential Rucaparib maybe has.

    assumptions (US only):

    new cases of ovarian cancer per year in the US: 20.000
    thereof mutated BRCA or “BRCA-like”: 10.000 (50%)
    market share rucaparib (assumed best-in-class profile): 5.000 (50%)
    average treatment duration: 8 months
    cost per month: 8.000 USD
    cost per patient: 64.000 USD
    sales forecast: 320 mio. USD per year

    These assumptions makes sense? Or is this misguided?

    Thanks as always!

    Hubert

  58. Hi Ohad

    Any comments to the Daratumumab presentation of the phase II data (Sirius) – are you still a bit dissapointed ?

    Any comments to the Humax-TF ADC data presented at ASCO ?’

    Regards
    Sukkeralf

  59. Hey Hubert
    Note also that 4-5 more indications will be studied as of right now.. In the presentation on sunday managment was clear that they are initiating other studies. This shall make it a blockbuster, in my view.
    Also it might fetch more than 50% market share, as the azn competitor is only targeting braca mutations, while ruca has no competition in the braca-like (35%)
    Dan

  60. Hubert (CLVS) – Your model makes sense. I would factor in a slightly higher monthly cost and there is upside to your market penetration assessment because BRCAness patients will be relevant only to rucaparib (at least in the initial years) so AZN and CLVS will compete for the 5000 BRCA patients but not for the other 5000 BRCAness patients.

    Sukkeralf (Genmab) – Data were good as expected, patients were very heavily pre-treated and effifcacy looks better than Kyprolis and Pomalyst. Although I was hoping for a higher response rate initially, dara is still the most promising myeloma agent in development and should become a multi-billion $ product. The main question is whether this justifies a $5B valuation.

    Dan (CLVS) – Thanks for this input, agree about potential utility in other indications (we know that PARP are active at least in prostate cancer) but I wouldn’t include these indications in a model right now.

    Ohad

  61. Hello Ohad,

    Greatly appreciate you insight. Do you have any opinion on Celldex’s Rintega data.I would also appreciate you thoughts on Aduro chances of success in there Pancreatic cancer trial.

    Thank You!!!

  62. Jordan (CLDX) – Actually I still haven’t formed a concrete opinion on the data. On the one hand there is a stat sig OS benefit + a tail in the survival curve of patients who are in long term remission. On the other hand, the survival benefit decreases with time, which reminds me of SNTA’s data but here the data is quite mature with a relatively small sample size.

    Re: ADRO – their chances of success imo are low as low as I believe the signal from the pancreatic cancer trial is unreliable due to small sample size. Hope I am wrong…

    Ohad

  63. Hey Ohad
    thanks. yes… regarding CLVS, are you thinking of adding? I wonder this considering you stated that you might have underestimated Ruca, and also they seem high on the list of potential target acquisitions.
    Regarding SAGE, it keeps going higher… is the valuation justified? I sold my shares around $58 thinking it would slip from there…
    Thanks very much!
    Dan

  64. hey Ohad
    If you have any time would appreciate your view on scancell ph1/2 trial at asco… Website for company is scancell.co.uk
    Thanks
    Dan

  65. Hi Ohad,

    Along the lines of smart-targeted chemotherapy, do you have any opinion of BIND or MACK? Despite some promise in early trials, they only seem to use more targeted versions of standard chemo-therapies instead of targeted versions of extra-potent chemo therapies as those used by SGEN or IMGN. This might allow for straightforward modifications of existing treatments, but do you think this is enough to make them compelling treatments after losses from binding, internalization, and intercellular degradation?

    -Bif

  66. Thanks for great post. With #EHA2015 next week and #ASCO2015 just ended, are you expecting any important data to be announced at #EHA2015?

  67. MEIP abstract for EHA next week shows very positive results in elderly AML. Moving into Phase III with Pracinostat seems like a certainty based on these results. Dr. Guillermo Garcia-Manero of M.D. Anderson is leading the trials. MEIP has a strong cash position with an EV of less than zero. What do you think?

    UPDATED RESULTS FROM A PHASE 2 STUDY OF PRACINOSTAT (P) IN COMBINATION WITH AZACITIDINE (AZA) IN ELDERLY PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML)
    Guillermo Garcia-Manero MD , Ehab Atallah MD , Samer Khaled MD , Martha Arellano MD , Mrinal Patnaik MD , Vanessa Esquibel , Katie Wood , Bruno Medeiros MD

    Guillermo Garcia-Manero
    Guillermo Garcia-Manero
    Label: EHA Latest recommended materials

    EHA Learning Center. Garcia-Manero G. Jun 13, 2015; 100709
    AbstractRate & Comment

    Abstract: P568

    Type: Poster Presentation

    Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45

    Location: Poster area (Hall C)

    Background
    Elderly AML patients, deemed unsuitable for intensive therapy, have limited treatment options. We previously reported a high initial response rate in the first stage of a phase 2 study of P plus AZA in this population (ASH 2014). This report presents updated results, which include additional patients.

    Aims
    The study was designed to evaluate the efficacy and safety of the combination of pracinostat and azacitidine in elderly patients with AML

    Methods
    Eligibility includes previously untreated AML (≥ 20% bone marrow blasts), age ≥ 65 years, unsuitable for intensive therapy due to co-morbidities and/or AML related features, and intermediate or high-risk cytogenetics. Study therapy includes P, 60 mg p.o. 3 alternate days/week for 3 weeks plus AZA, 75 mg/m2 /day 1-7 or day 1-5 and 8-9 either s.c. or i.v. with cycles repeated every 28 days until progressive disease, lack of response, or intolerance. The primary endpoint is CR+CRi+ morphologic leukemia free state (MLFS) per IWG criteria. Response assessments occur at the end of cycle 1 or 2 then every other cycle or when clinically indicated. A Simon 2-stage statistical design is utilized with the following assumptions: null=0.10, alternate=0.25, α=0.10, power=0.90. Stage 1 n=27 and total stage 2 n=40.

    Results
    Between 12/2013 and 12/2014 50 patients from 15 study sites were enrolled. At this time, 47 are evaluable for efficacy. Baseline disease characteristics for all patients include: median age 75 (range 66-84); 32 de novo AML, 13 evolved from AHD, 5 treatment-related; 28 intermediate-risk and 20 high-risk cytogenetics and 2 unknown; baseline bone marrow blast counts ranged from 20% to 89% with a median of 40%. The primary endpoint of CR +CRi +MLFS has been observed in 22/47 evaluable patients (47%) to date, including 14/47 (30%) CR. Current median duration of response is 15+ weeks (range: 1– 48+ weeks). Disease progression has not been observed in any responders. 30 patients continue on study (range 11- 52+ weeks). The 60-day all-cause mortality rate is 10% (5/50). Median overall survival has not been reached. Treatment emergent adverse events (TEAEs) Grade ≥ 3 seen in >5% of patients: febrile neutropenia 30%; thrombocytopenia 22%; neutropenia 10%; cellulitis 10%; anemia 8%; fatigue 8%; sepsis 6%, and pancytopenia 6%. TEAE’s leading to study therapy discontinuation: peripheral motor neuropathy (1), parainfluenza (1), atrial fibrillation/prolonged QTc/(1), subdural hematoma after a fall (1), and sepsis (3).

    Summary
    P plus AZA produces a high rate of durable responses in this AML population. Updated data, including EFS and OS estimates, will be presented at the meeting. These phase 2 data warrant definitive evaluation in a phase 3 study.

    Keyword(s): Acute leukemia, Elderly

    Session topic: Acute myeloid leukemia – Clinical 3

  68. Dan (CLVS) – I am not considering adding as my exposure is already rater high. Although I no assign more value to Rucaparib, which could easily be an ~$800M drug just in ovarian cancer, there is an overhang on rociletinib following the lower than expected PFS.

    Re SAGE – Agree about valuation getting rich if you rely on SRSE as the sole indication. P3 is just starting later this year so they need other catalysts (data from other indications) to keep the stock grinding higher.

    Louise (RXII) – Sorry, don’t know them well.

    Wildbiftek (BIND/MACK) – So far their clinical data is underwhelming imo but the rationale for targeted delivery by nano-particles is there. I believe they can address settings/targets that are not suitable to ADCs with highly toxic payloads pursued by IMGN/SGEN.

    Ulrike (LXRX) – Sorry, don’t know them well.

    aoganes – My EHA watchlist comprises AGIO (both IDH1 and IDH2), BLUE, PRTA and ALNY(C5 siRNA ).

    Richard (MEIP) – The problem with such trials is the difficulty to distinguish between pracinostat’s effect and that of Vidaza. Their recent MDS failure demonstrates this challenge.

    Ohad

  69. Ohad

    you had stated in a prior post that if a pharma company is looking for oncology assets they should look at CLVS first.if that was to happen would a 5-6b acquisition be in the ballpark?Does the results of there lung drug damper the chances that can happen?

  70. Thanks Ohad for your Watch list #EHA2015.
    A quick question if I am reading this right – positive tumors?:
    “For example, Roche may be able to pursue PD-L1 negative tumors as a fast and cheap route to market for new immuno-oncology combinations”

  71. Thank you for the reply to my FMI question….

    If you had to pick a few (3-4) of the best ‘larger’ pharma companies, i.e. Roche, Pfizer, BMY, Abbott, etc, etc…..which would you feel most comfortable/confident in putting your money in for a future investment.
    (If I simply wanted to diversify some new $ into the sector)

    Thank you

  72. dave (CLVS) – The recent lung cancer data certainly creates an overhang on the drug but based on market reaction, the general view is that rociletinib is as good as AZD9291 and that the PFS difference should be attributed to baseline patient characteristics. This is also demonstrated by Astellas’ molecule which generated a 61% response rate in Japan vs. 36% in the US (small numbers and cross trial comparison).
    Bottom line, CLVS remains an attractive acquisition target. Good data for lucitanib could make it even more attarctive.

    Den (ADAP) – I still prefer not to discuss CAR/TCR companies.

    Alex (STEM) – not yet, sorry…

    ruediger (XENE) – I like it a lot and would like to add some in the near future. NaV1.7 is probably the most validated pain target and having two complementary programs for systemic and local administration makesa lot of sense.

    Anna – I was referringto PD-L1 NEGATIVE tumors which are not likely to respond to PD-1 monotherapy. In these patients it will be easier to show the benefit of adding a new immune checkpoint blocker.

    ryan – Sorry but I don’t invest in large pharma stocks so cannot help there.

    Ohad

  73. Ohad
    Any comment on SGEN – Unum deal. It is early but looks interesting – ACTR+CD8/4-1BB/CD3.
    Any opinion about XNCR – they also target Fc domain. They have huge early stage collaboration w/ MOR, BI, MRK, Jansen, ALXN,

  74. Ohad,

    I am a first time poster though I have enjoyed reading your blog and greatly appreciate your sharing your thoughts with people for some time. Its also very admirable that you respond to everyone!

    Would like to hear your thoughts on two things:
    1-Do you follow/have an opinion on a tiny austrailian company CUV.AX / CLVLY approved late last year in EU for EPP and pursuing Vitiligo (and possibly other skin conditions)?
    2-With SAGE-547 open label results in 4 post-partum depression patients does it make sense for MRNS to try IV ganaxolone here as a first indication?

    Thanks,
    Maurice

  75. andre (SGEN) – The deal with Unum is definitely a creative step that may diversify SGEN’s portfolio beyond ADCs in the long run. They made a bold bet on an unusual CAR format, which increases the risk/reward amplitude. I don’t see any immediate implications, as the market is still focused on maintenance Adcteris and SGN-33A.

    Re: XNCR – They have decent technologies but valuation is too high considering the early stage of their pipeline.

    Maurice – Sorry, don’t know CUV.AX.
    Re: SAGE/MRNS, today’s results are very encouraging, only 4 patients but the change is so striking. If I were MRNS I would try to leapfrog SAGE by pursuing this indication with oral ganaxolone. SAGE intends to develop an oral drug for this indication eventually.

    Ohad

  76. Hi Ohad

    Not sure if you have commented before and I missed it but
    have you any thoughts on FGEN to share?
    Thanks for your generous sharing !

    Gene

  77. Hi Ohad, In light of the new data of SAGE, are you planning to add more shares?

    Thanks!

    Jinyu

  78. Greetings (from Finland) Ohad,

    I recently stumbled across your blog, while doing some dd on $IMGN, and I instantly noticed that you had plenty of well-informed insight on stocks and a rigorous approach towards market research, and I’ve been waiting for every one of your posts with bated breath ever since.

    Anywho, I was wondering, what’s your take on $TGTX and $XLRN and how big of an impact would you suspect EHA (their presentations) having on them? Also who do you think will be the biggest winner of EHA? $AGIO, $BLUE, $ALNY?

    Bonus question, (haven’t really done much dd yet but might as well ask at least to see if i should further proceed or not, if you should happen to know the stock) is $VTAE any good?

    Thank you very much in advance and keep on posting!

    Best regards,
    Ilmari

  79. Hi Ohad,

    You mentioned TRVN as a stock you have been following. What’s your opinion on this company?
    When is your next portfolio update? Looking forward.

    Thanks as always ,
    Chris.

  80. Jinyu (SAGE) – I don’t plan to add more shares as I am happy with the current exposure (5% of total portfolio) given the rich valuation ($2.5B) and the time it will take to get randomized data in SRSE or PPD. Also, now that investors finally start to realize MRNS may have a similar drug they might want to redistribute some of the funds invested in SAGE to MRNS as a hedge.

    Ilmari (TGTX, XLRN) – Thanks and welcome aboard.

    TGTX – Although their drugs clearly work, I am still concerned about TGTX’s ability to compete with similar drugs which are more advanced. On the PI3K front the market is still nascent (and so far Zydeliq sales are disappointing) but the CD20 market will be almost impossible to compete in with generic Rituxan and increased use of Gazyva.

    XLRN – I like luspatercept’s opportunity in MDS, which is an attractive niche irrelevant to competition (BLUE). In general, their focus on TGFb superfamily is exciting for other indications in the long run but it is hard to ascribe significant value to these indications at the moment. I prefer to wait until valuation gets more attractive.

    Regarding the winner of EHA, the three names you mentioned are coming into the meeting with fairly high expectations so from an investor perspective risk/reward is unfavorable imo. To me ALNY is more intriguing as they will need to show significant knockdown in order to compete with ALXN.

    Sorry, not following VTAE.

    Chris (TRVN) – Yes I still it and expect positive results in abdominoplasty next Q. Valuation is still reasonable at ~$250M, I intend to add it to the portfolio, looking for a good entry point. Will try to post a portfolio update on Sunday.

    Tom (ASND) – Sorry, don’t know them well.

    DJ (EPZM) – So far clinical data is underwhelming imo.

    Ohad

  81. Hi Ohad
    any reasons EXEL delay the rcc data release?
    in case of a positive outcome ,how the stock be affected? up 80-100 %?

    Thanks

  82. Hi Ohad,

    What do you think of the big drop for ESPR? Do you think the market is overacting on Sanofi’s news?

    Thanks,
    Cloud

  83. I like TGTX being in since last year and very happy. Mkt value will exceed 2 $B
    I am glad I didn’t buy ESPR. -25% today after REGN Adcom FDA pass…I won’t touch it for the moment

  84. Hi Ohad
    the selloff in ESPR is because Praluent approved or because its limit use to patients projects on etc-1002, or both?
    thanks

  85. Hi Ohad,

    regarding Genmab, the valuation looks quite high at the moment but the stock ist still climbing. Do you think it’s overpriced? And: Do you have any expectations for Genmab in the future (mid- and longterm)?

    Thanks for sharing your opinion!

    Martin

  86. Hey Ohad,
    one question regarding XENE. Results of TV-45070 PII in osteoarthritis will be released soon. What would you regard as a positive outcome? And are you optimistic for that?
    Thanks as always!
    Ike

  87. Alex (EXEL) – From what I recall they spoke about Q2, which isn’t over yet. Yes, I would expect a 80-100% move with positive results.

    Cloud (ESPR) – The reaction is legitimate in principle because the panel was less receptive regarding broad use of new LDL lowering drugs and that may apply to ESPR in the future. Since ESPR is still far from submission, it is hard to predict the regulatory environment. Long term ESPR is still a valuable take out candidate.

    Alex (ESPR) – Because of it limited proposed use (which will not necessarily be represented in the label).

    Martin (GEN) – Valuation is too high imo. We decided to sell.

    ike (XENE) – Yes, I am optimistic on that and just added today ( see post I published).

    Richard (CALA) – So far no signs of efficacy, maybe they will see something with biomarkers for patient selection…

    Ohad

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