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I know you asked Dew, but I have been compiling the following list of competitors and thought it might be helpful. All listed below provide next-gen sequencing, actionable reporting, and consult for treatment regimen. Only Foundation Medicine and CollabRx (CLRX) are publicly traded.
Foundation Medicine (Foundation One/Heme) http://foundationone.com/
NantHealth (Nantomics) Patrick Soon-Shiong http://nanthealth.com/nantomics/
Caris (Caris Molecular Intelligence) http://www.carismolecularintelligence.com/
Genospace with Pathgroup (SmartGenomics) http://static.squarespace.com/static/541c4fd3e4b000f167fdfe1d/t/544ea536e4b01e689a1a215e/1414440246179/GenoSpace+PatthGroup+case+study.pdf
CollabRx (CancerRx; TherapyFinder) http://www.collabrx.com/products/
MolecularHealth (TreatmentMAP) http://www.molecularhealth.com/oncologists/evidence-based-treatment-strategies/
Personal Genome Diagnostics PGDx (CancerXome) Vogelstein http://www.personalgenome.com/approach.html
SymbioDx (Symgene) http://www.symbiodx.com/ngs
GenomOncology (GO Clinical Workbench) http://www.genomoncology.com/clinical/
N-of-One/Neogenomics (PrecisionWorks/Treatment Roadmap) http://www.n-of-one.com/platform-products/
Syapse/UCSF http://www.syapse.com/blog/ucsf-announces-collaboration-with-syapse-to-power-genomic-medicine-initiative/
MolecularMatch (beta) https://www.molecularmatch.com/learn
For biotech events I recommend this calendar, you can filter by event types. Although I noticed several 'Analyst Days' are missing, I think it depends on the title the company uses in the press release.
http://www.biotechnologyevents.com/events
Yes, that's from a month ago...indeed someone (other than me) agreed it needed to be clarified.
Less than 10% present in AP at diagnosis, so if positive that's only ~1,000 additional patients WW, but good candidates for most potent drug first.
Not sure about the rest of the pipeline but the oncology candidates would have been newsworthy....about 15 years ago. If the rest of the pipeline is also dusted off someone's shelf I would sit this one out.
KD018 was PHY906 (chinese herbal)…increases therapeutic index of chemo by reducing side effects
KD019 was XL647 (EGFR/VEGFR2/HER2 TKI)….3% response rate in EGFR-resistant NSCLC
KD032 was salirasib (salicylic acid derivative)….0% response rate KRAS NSCLC
Depending on the sensitivity of the PCR used, clonally evolved CP could be the majority of frontline. It's not clear from the protocol what level of which mutations qualify are screened. I get your clarification on stage, but it's still misleading to leave the title as CP, and end points that refer to "time to accelerated phase" if they all start out AP.
Forgot to update the title, and mislead the entire CML community?
I'd have to give Dr. Cortes more credit than that. I think the answer is found in exclusion criteria #8:
E. Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has been historically been included as a criterion for accelerated phase. However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution and no other criteria for accelerated phase will be eligible for this study.
Maybe the trial is now limited to chronic phase with documented clonal evolution.
Could also be related to this, specifically mentions competition with FMI...
http://www.forbes.com/sites/matthewherper/2014/07/31/worlds-richest-doctor-buys-worlds-most-powerful-dna-sequencer/
30% is more consistent with WW* incident pools...
CML Ph+ (95%)......14,500 1L (~7,000 2L)
ALL Ph+ (25%).........4,300 1L (~2,000 2L)
*developed countries only
Sorry, topic is TGTX insiders and was meant in reply to bellweather1's question...
BW...just be careful as the CEO's time frame may be shorter than yours...
In Jan. of this year he became Exec. Vice Chairman of Coronado Biosciences (CNDO) and was awarded 4MM shares (6MM total), vesting periodically through 2019. I'm not sure how a CEO in New York manages to simultaneously be Exec. Vice Chairman for another company in Maine, but likely one of these is only temporary. Of course this could be a good thing if the trial data is strong and a buyout follows. Its unlikely a 14-person company in Columbus Circle (no lab space) will develop or commercialize either compound.
http://www.coronadobiosciences.com/about-us/management-team.cfm
Just my thoughts, congrats on the substantial gains.
Okay, okay. You've had your fun, come on back home now. Really, wouldn't you rather be down over 7%?
That's nodal response, as in lymphocyte count, which is a secondary measure of activity in CLL. ORR is always less than nodal response, as in ibrutinib had 100% nodal with 66% ORR, and IPI-145 had 84% nodal with 47% ORR. So if TG-1202 can go from 67% nodal to 85% ORR then its a breakthrough.
We agree, since combos have broken the 80% ORR barrier with acceptable safety there's no going back to monotherapy. I'm not in this stock, but I had the same optimism with IPI-145 based on presentations like below, but ibrutinib/idelalisib changed everything, IPI-145 immediately became past tense. I hear you on 1202's safety but without an ORR on the table I remain unconvinced.
http://web.oncoletter.ch/files/cto_layout/Kongressdateien/WCLC13/CLLFlinn.pdf
Do PD-L1 populations overlap EGFRm in NSCLC?
PD-L1/PD-1 immunotherapy is coming to NSCLC, but the question arises will it take market share from known driver mutations such as EGFRm (15% ADC) or ALK (5% ADC), or is the PD-L1/PD-1 population (50% NSCLC) substantially independent, i.e. consisting mostly of the 45% driver-unknown population? Two studies below suggest conflicting answers:
No correlation view
insert-text-here
Strong correlation view
insert-text-here
That's helpful...but I still think its too early to call for BIC, and being the best PI3K-delta in CLL doesn't mean you have a market. Combos with BTK or Mabs could be the answer but those results are 3-4 years out for 1202. By the way IPI-145 achieved 89% nodal response in 2 months, but really we need to be comparing ORR, not nodal. Anything over 50% (with more patients) is competitive, but BIC would need to break 60%.
I'm new to TGTX but have grown cautious of PI3K inhibitors, granted mostly as single agents in solid tumors. Idelalisib/Ibrutinib have set the bar in R/R CLL that candidates must either meet at each stage or differentiate. Safety could work, but I see higher grade-3 AE's in the abstract than idelalisib's Phase 1 from ASCO last year (see link). Don't you think 3-4 fold concentrations will also impact toxicity? I'll be looking for firmer signs of activity from the presentation, more patients and actual ORR, a far more important comparator for efficacy in CLL.
http://meetinglibrary.asco.org/content/116074-132
I was referring to this trial from ASH 2013...100% nodal response at 6 months.
https://ash.confex.com/ash/2013/webprogram/Paper61843.html
I would be careful here with TGR-1202....the list of PI3K inhibitors with impressive activity at early stage only to disappoint in Phase 2, continues to grow. I know its early and 6 CLL patients is too few to judge, but 67% nodal response (down from 75% at ASH) does not compare favorably with single-agent idelalisib's 81%, not to mention ibrutinib's 100%.
I find BioSpace to be the best daily news feed...
Good balance of science and business of Bio/Pharma.
http://rss.biospace.com/newsstory.rss
or use:
http://www.biospace.com/news.aspx
I also subscribe to FierceBiotech.
http://www.fiercebiotech.com/feed
2da...thanks for doing the thankless...
We are wiser for your contributions, and hopefully on track now to come back even stronger. It will take a bit longer to launch, but your emeritus status already reserves you a front row seat.
You will be missed.
jaybe
I don't think a new patent is needed...
Just means they have to repeat dose escalation and represent all efficacy and safety data.
I'm around but as Dough says I'm a bit sidelined by spotty wifi in various EU countries. I'm reading all posts but unable to research in support of any novel contributions. From what I'm reading you guys are killing it anyway.
Must admit I was hoping for 70%+ response rate in Criz resist. but I'll take the 100% in Criz naive as a consolation. I think Jesspro and others are right that BIC will now come down to duration of response.
Brain met activity should bump up the Ariad target pool of 14,000 by another 6,000 or so, basically all stage 3-4 ALK+ pts. with or without BM. And we can add back in the 2L failures due to BM from LDK and Alectinib and soon ROS1 and I think '113 could target 30,000+ patients a year.
Also room for more "pipeline-in-a-drug" molecules...
Lease terms are favorable with escalating rent of $5M in 2015, up to $21M by 2019. Of note, 75-125 Binney Street will be 25% larger than new neighbor Biogen at 225 Binney Street.
Glam shots of new digs
http://www.tocci.com/2009/11/75125-binney-street/
Download updated corp presentation from 9/9/13...
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=7&ved=0CFMQFjAG&url=http%3A%2F%2Fphx.corporate-ir.net%2FExternal.File%3Fitem%3DUGFyZW50SUQ9NTE4ODE1fENoaWxkSUQ9MjAxODQwfFR5cGU9MQ%3D%3D%26t%3D1&ei=Ogw1UvOVGrbe4APgnoCwDw&usg=AFQjCNGsMsfur9BgYPLz_XnVKh1OVxTGQA&sig2=1dEdEOVe6XV983j3pnPYug&cad=rja
About 20% present T315I in TKI-naive...
When randomized 50/50 this automatically reduces imatinib's MMR by half, or 10%, versus Pona. This also increases Pona's MMR by 7.5% since 75% of T315I patients achieved MMR in PACE trial.
So automatic 17.5% delta on MMR, and as you say throw in a few more of the 49 additional mutations shown to be resistant to imatinib but sensitive to Ponatinib and voila...its EPIC!
Another strong call for best drug first...
Recent article reviews origins of TKI-resistance via clonal mutations and suggests frequent TKI switching may lead to re-emergence of latent mutations previously sensitive to original the TKI. In other words the more you switch the greater the chance of developing resistant mutations.
http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2013490a.html
56% AE's at lowest dose is right...
Its 15/27, sorry for typo, but I'm sure you already checked the poster yourself.
Not so fast on labeling Clovis as "better tolerated"...
I'm not trying to bash Clovis here but the ASCO data shows 11/27 (56%) at lowest dose (up to 600mg) with adverse events attributed to drug. And since best efficacy is presented at 900mg BID then one should note at this dose the adverse events attributed to drug of 4/6 (67%), with 2/6 (33%) at grade 3/4. Note AP26113 poster reports adverse events "regardless of treatment relationship".
I know the enrollment is tiny but my point is its way too early to say CO-1686 is better tolerated than '113. This will play out in Sydney at World Lung conference, end of October.
iAndy, those are the figures I used...
My numbers assume more burn than Ed forecast. Japanese office is new, and we don't know how many pivotal trials come online, but to run out of cash in 2014 we'd have to burn $110M+ per quarter (I'm assuming $80M in my model).
Since ISTs are small proper Phase 2 trials are required in RET-NSCLC, FGFR-SCC, MTC, AML, Endometrial, and new FGFR-NSCLC, but unlikely any of these will be a pivotal trial in 2014. I think its reasonable to assume only pivotal for ALK+ Criz-resist., GIST, and possibly ALK+ Criz-naive.
I agree sub-$100M in cash would considered risky and attract vultures, but since the path to consistently positive earnings is clear and only one quarter away (Q1 '15), I don't think it limits operations.
JMHO...I will be happy to be proved wrong by more pivotal trails and new molecules.
Can someone summarize why another offering is needed?
My back of napkin assumes burn of $70M in each Q3 & Q4, and say $80M in each quarter of 2014, totaling $460M thru YE '14, offset by sales of $18M in Q3, $27M in Q4, and conservatively $210M for all of 2014, totaling $255M in revenue thru YE '14. So when current cash of $351M gets reduced by net $205M of losses over the next 6 quarters you still have $146M cash at YE '14.
Since all quarters post-2014 will have increasingly positive earnings why is any type of financing necessary?
Its listed at Scottsdale, under 'Lymphoma'...
The 2012 AACR poster for TSR-011 is on Tesaro's website, very respectable IC50's for ALK and gate keeper mutantion L1196M. No info on toxicity or of course in vivo response.
But still, why not register on clinicaltrials.gov? Why wouldn't you want to accelerate enrollment by broadcasting trial around the world?
I would assume so since abstract was from April...
Anyone know what it means to NOT list a trial on clinicaltrials.gov?
Why would Tesaro not register this trial?
Not just oral but presentation but "not to be missed"...
Scroll down to Lung Cancer - Metastatic and Localised/Systemic
http://eccamsterdam2013.ecco-org.eu/Event-Overview/Abstracts-not-to-be-missed.aspx
Also today's abstract does include 5 additional patients (4 ALK/ 1 EGFR)from the ASCO abstract, so a press release is warranted. ALK+ responses increased from 56% at ASCO to 62% (note this includes all doses). In ALK+ with prior Crizotinib (case for imminent pivotal trial) responses increase from 67% to 73%. No additional response from EGFR patient.
Longest response increased from 40 weeks to 48, ongoing. Five more months of data will be presented at ESMO.
No abstracts for LDK, Chugai, or Clovis, but new drug TSR-011 is threatening to be competitive.
Good point...maybe something pre-clinical by Dec 3rd?
The abstract filing deadline for AACR 2014 is December 3rd.
Here's the (unofficial) history of Ariad's unwrapping of new molecules:
Rida AACR 2004
http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/573-b?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=AP23573&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
Pona ASH 2007
http://abstracts.hematologylibrary.org/cgi/content/abstract/110/11/1032?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=ap24534&searchid=1&FIRSTINDEX=0&volume=110&issue=11&resourcetype=HWCIT
AP26113 AACR 2009
http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2009/2_Annual_Meeting/3738?maxtoshow=&hits=10&RESULTFORMAT=&author1=clackson&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
???? AACR 2014?
My WAG...Ariad takes on the "undruggable" KRAS.
Harv did well, he's quite polished now....
In my opinion Harv exudes confidence when he speaks. I really think its remarkable the breadth and depth of topics he can speak to with ease...corporate, commercial, scientific, clinical, and medical (from doctor/patient perspective). I know this is what bioCEO's should do but compare with recent transcripts from Exelixis' Michael Morrissey or Clovis' Patrick Mahaffy. Harv comes as off as objective, informative with being condescending or cocky, and genuinely concerned about progressing standards of care in parallel with developing Ariad's vision. Of course this attitude coincides with owning next-generation drugs.
Lots of positive comments on Pona in GIST with several references to potential fist line randomized trial as next step. '113 pivotal trial (single arm Phase 2) in resistant ALK will start "very soon" with a Phase 3 randomized trial starting next year as required for accelerated approval strategy. I think this will allow for potential filing by end of next year, with mid-2015 approval.
A little disappointing next molecule is 12-18 months out.
Example of what Foundation Medicine did for HER2...
http://www.foundationmedicine.com/pdf/news-releases/2013_06_02_FMI_HER2_ASCO_FINAL.pdf
I think we will see similar press release soon specific to '113 pursuant to collaboration announced last November.
The abstract says 8.5% additional ALK patients...
So I was off by 1%, still 12-14% of NSCLC is triple the currently assumed population. Best part, we will have Pfizer, Novartis, and Roche/Chugai handing out flyers to all MD's in no time.
Let's hope Foundation Medicine comes through for us with a best-in-class diagnostic for ALK detection.
Doug this is huge...Dr. Camidge is ESMO presenter...
The article basically states that ALK is not just 4-5% of NSCLC (with ALK+ levels above 15%) but an additional 9.5% (10% of the non-ALK 95%) with ALK levels between 10-15% may also benefit from ALK inhibitors. That's a total of 15%, triple the currently assumed population for ALK inhibitors.
Of course then we could add another 1.5% for the ALK+ patients resistant to Crizotinib demonstrating mutated EGFR (reference the article you posted earlier today), and bring the total to 16.5%, but then we might as well include the 7-8% with T790m (50% of EGFR)for a grand total of 24% of all NSCLC.
Anyone think 300,000 patients per annum will add value?
Let's go ESMO!
I think you are right about ESMO data...
I originally thought abstract release this Thursday would have additional data, but after second look, the data presented at ASCO used April 17th as cut-off, same day as deadline for ESMO abstracts (coincidence?). So I think we have to wait until Saturday the 28th, 5:27AM EST to get the good news.
Last year data cut-off for ESMO was just one week prior to meeting so this would mean 5 additional months since ASCO data, with 2-3 months of enrollment in cohorts #1-4 (assumed early July). Patients who received the 180mg dose in Phase 1 convert to Phase 2, so potentially 12-18 months on study. In my opinion duration of response is the final piece needed to be confirm best-in-class.
Regarding Pona crossing the BBB...
Most TKI's cross the BBB in fractions of plasma concentrations, Pona crosses in multiples.
See excerpt below from world patent on use of Pona in neurodegenerative diseases, click on 'Description' tab and scroll down near bottom to Table 1.
"Ponatinib was 2.79 times greater in brain relative to blood on an area under the curve (AUC) basis and 2.26 times greater on a the basis of maximum concentration observed (Cmax). The observed elimination half-life was also longer in brain than in blood."
http://patentscope.wipo.int/search/en/detail.jsf?docId=WO2012139027&recNum=6&maxRec=252&office=&prevFilter=&sortOption=Pub+Date+Desc&queryString=FP%3A%28ariad%29&tab=PCTDescription