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It's easy, start with $1.3B sales for 2017...
That includes 1st line CML, launch of 2nd indication in GIST, and launch year of '113 in ALK R/I.
Then assume profit margin of 50%, divide by 184M shares and you get $3.50 a share net EPS.
Then assume PE of 30, so $105, and discount 25% per year back to 2013, and your get $33 PPS today.
Bob's your uncle.
Maybe this explains meeting with NVS...
http://www.ncbi.nlm.nih.gov/pubmed/23539538
Midostaurin has been in the lab for over 10 years, still not approved for an indication. Appears to overlap with several Pona targets, FLT-3, c-KIT, VEGFR-2, PDGFR . Most current trials are combo studies with chemo in AML.
Latest trial results from ASH 2012 leave something to be desired:
https://ash.confex.com/ash/2012/webprogram/Paper48129.html
I think we will see many more Pona combos as labs around the world understand Pona just makes their drugs better. I sense a nice revenue stream flowing with little to no outlay.
Ariad on LSR Watchlist for 2013...
http://www.thelifesciencesreport.com/pub/htdocs/372
Don't forget ASCO abstract for '113...
8) Abstract #8031
First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: Updated results.
D. R. Camidge, MD, PhD
Poster Board: #20
Hints of potential for dual ALK/EGFR inhibition...
Hey Harvey, let's get that RDP2 going, its almost mid-2nd QTR.
http://iaslc.org/assets/News-Releases/JTO/May-JTO-Boland-MET-and-EGFR-mutation-identified-in-ALK-final.pdf
CT Order pertains to terms of new lease...
From CT Order...
ARIAD Pharmaceuticals, Inc. submitted an application under Rule 24b-2 requesting confidential treatment for information it excluded from the Exhibits to a Form 10-K filed on March 1, 2013....accordingly, excluded information from the following exhibit(s) will not be released to the public for the time period(s) specified:
Exhibit 10.2 through March 1, 2023
From 10-K...
10.2 Lease Agreement, dated January 4, 2013 between ARIAD Pharmaceuticals, Inc. and ARE-MA REGION NO. 48, LLC (for lease at 75 Binney Street and 25 Binney Street)**
Isn't that an increase from $3M to $7.8M.
More than 325 patients in the U.S. are now being treated with Iclusig obtained commercially based on physicians’ prescriptions. Importantly, this does not include any patients using the initial Quick Start 30-day supply.
From April 4th press release. So these 325 are paying for drug.
The most comprehensive guidelines come from NCCN...
Also referenced on page 3 of the RengenceRx piece.
See link for summary of NCCN guidelines, check out page 12, where Pona is recommended first for all mutuations. Ponatinib summary on pages 20-26. I like the summary slide, page 26, "[Ponatinib is]expected to significantly improve outcomes of CML and Ph+ ALL".
(By the way if you want to see what a dirty drug profile looks like check out Bosutinib on page 16.)
https://winshipcancer.emory.edu/media/file/2013%20Nursing%20Symposium/Nikki%20Wilson%20-%20Novel%20Therapies%20for%20the%20Treatment%20of%20Multiple%20Myeloma%20and%20Leukemia.pdf
Best in class for ALK will be demonstrated at ASCO. However, a teaser for this potential will be presented this Wednesday at AACR.
From abstract #5655..."Importantly, since AP26113 maintains potent activity against mutant forms of ALK and ROS1 at concentrations substantially below its human trough concentrations these data suggest that AP26113 may be able to prevent the emergence of drug-resistant mutants in NSCLC patients."
"All patients...should be tested for ALK and EGFR..."
Small positive today for '113 in form of new multi-organization recommendation for molecular testing of all adenocarcinoma patients.
http://www.sciencedaily.com/releases/2013/04/130403200052.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29
A good time to buy call options?
That would be today, or yesterday, or anytime last week.
I think a little AACR/ASCO buzz leading into earnings call will set trajectory upward from now to end of April. Target: $25-26 pre-ASCO.
Anything goes post-ASCO. We will see ALL data at ASCO including several EGFR patient responses.
Just posted this comment on The Street article...
I just couldn't help it.
Comment:
So let me get this straight, your source feels Iclusig is a "dirty drug" due to similar side effects and no improvement on efficacy. So since all second generation TKI's for CML demonstrate comparable safety and efficacy then Pfizer, Novartis, and Bristol-Meyers must have dirty drugs too, right? Halting the EPIC trial early? Perhaps...but for accelerated approval. Have you seen the MyCR data from the PACE trial for Iclusig in patients previously treated with only one TKI? Here's a recap: Nilotinib 40%, Dasatinib 45%, Bosutinib 36%, Iclusig 84%. Regarding efficacy I suggest relying on leading MD's in CML treatment for assessment of efficacy, not sell side analysts. A few examples below for your convenience.
Dr. Jorge Cortes -
“These results show that ponatinib has outstanding activity regardless of the stage or presence or absence of mutations associated with resistance, and responses are durable. "The side effects are very acceptable, like all the tyrosine kinase inhibitors they all have some side effects."
Dr. Neil Shah -
“This drug has the potential to be a best-in-class agent that may be completely invulnerable to single-kinase-domain mutations,” says Neil Shah, the UCSF hematologist who treated Galliart. “I’m hopeful that it really will remove single-kinase-mutation–mediated resistance out of the picture.”
Dr. Hagop Kantajian-
"The standard of care in refractory or relapsed patients to multiple TKIs doesn't exist. What we have usually is some data on either dasatinib or nilotinib in patients who have failed imatinib and one of the other TKIs. This drug is effective even when those three drugs have failed. So it establishes a new standard of care of highly effective therapy. If you ask if we can anticipate how this drug will compare to the other TKIs in the same setting, I think this drug will be more effective than the second-generation TKIs in the setting of salvage therapy, but that remains to be seen. But this drug is also highly effective against the T315I mutation."
Was that a bear hug? Prefer the short squeeze...
That's why I don't have stops...
Just buy orders for Jan '015 35 Calls...
Thanks Rachel et al for helping me add to my collection.
Mike King's preview for April 6-10 AACR...
With a couple of shout-outs for Iclusig...
http://www.oncbiz.com/blog/2013/03/a-different-kind-of-football-aacr-just-weeks-away/
That's an excellent one. New to me in 2013, but I see Biomaven posted in 2011. It's one of the main sources for my next indication summary of Pona:
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=85764510
But note Timmy C, Willy S., and others are part of the et al. The upcoming AACR presentation appears to be 3rd-party, albeit a Pona collaborator.
Do you think Dr. Druker dusts off the diagnostic in light of EMA approval for 1st line T315i?
Interesting AACR abtract from Dr. Druker Re: Ponatinib...
Found this one browsing the AACR abtracts for '113/Pona related content. Heavily edited by me below.
Abstract Number: 4971
Presentation Title: FGF2 promotes resistance to ABL kinase inhibitors in CML
Presentation Time: Wednesday, Apr 10, 2013, 8:00 AM -12:00 PM
Author Block: ......Brian Druker
Abstract Body: ...This screen identified Fibroblast Growth Factor 2 (FGF2) as a factor that mediates kinase inhibitor resistance in the CML cell line K562.... Inhibition of both FGFR and BCR-ABL in the FGF2 imatinib-resistant outgrowths was synergistic in promoting cell death.....Further evidence that FGFR may be important in kinase resistance is emerging from clinical trials of the novel ABL inhibitor, ponatinib. Although ponatinib was specifically developed to bind BCR-ABL with the T315I mutation, it is also a multi-kinase inhibitor, including inhibition of FGFR in the low nanomolar range. To wit, ponatinib was able to suppress FGF2 imatinib-resistant outgrowths in the low nanomolar range whereas imatinib, dasatinib and nilotinib were ineffective, even at high doses. In clinical trials, ponatinib has proven effective not only against T315I mutated BCR-ABL, but also in patients with minor or even no mutations of the ABL kinase domain (in press)...
Why aren't we focusing on T315i?
7,000 EU patients per year times 20% T315i mutation equals 1,400 patients per year. Add another 25% for 3rd line (50% of imatinib R/I times 50% for dasatinib/nilotinib R/I) and you get 3,150 total EU patients per year...eligible now and 100% Iclusig's share of the market. US market share is more like 50% of US population of 2,500 switching TKI's, or 1,250 per year.
In short the EU patient population based on the label is nearly 3 times the US. Of course this assumes we get T315i testing to be standard of care.
How can she not raise Pona's DCF value with the prospect of 2-4 new indications now public. Isn't a new indication for Pona ahead of '113 in the pipeline? Pona will see revenue from a new indication before '113 sees any.
The challenge for GIST is competing against a generic imatinib, and therefore having to run a head-to-head P3 trial to prove superior efficacy for 1st line use. This we will do, but could run approval and therefore appreciable sales into 2018.
Note the comparable (eligible for TKI in newly diagnosed) patient count for CML would be 13,300 WW. So GIST potential is 4 times the revenue of CML.
Place your bets for Pona's next indication...
Listed below are potential new indications for Ponatinib based on published pre-clinical data and current IST's.
Indication (target) / % Mutation / WW Annual Pts. w/Mutation
1. AML (FLT-3) / 30% / 4,130
2. GIST (KIT/PDGFR) / 90% / 50,800
3. Endometrial (FGFR2)/ 30% / 159,900
4. SCC (FGFR1) / 21% / 101,400
5. MTC (RET) / 72% / 4,600
6. Bladder (FGFR3) / 50% / 191,500
7. Breast (FGFR1/2) / 14% / 193,200
8. NSCLC (RET+FGFR1/2)/ 3.5% / 22,500
9. GBM (VEGFR) / 40% / 60,000
10. Gastric (FGFR2) / 4.1% / 40,550
In my opinion we will see two of these trials start this year. I think a survey is called for here, no?
In case you are wondering....if you add up these patients and assume 30% for 2nd line use, and then another 30% for market share, and yearly cost of treatment of $100K...you get annual sales of $7.45B...just sayin'...
Vive Le Clusig!
My main point is that only a few hundred patients will be on drug in the first year long enough to determine adverse or ineffective results. 600 patients will start after June and therefore not assessed for discontinuation until end of year.
Just saying that her math assumes an extremely low growth rate. If approx. 300 patients are online this quarter then It follows to expect at least 1200+ for the year, which would yield $70-80M. Also I get this sense her "ramp" calculations do not account for the the fact that everyone stays on treatment for at least a few years, there is no appreciable discontinuation beyond a few percentage points.
Rachel has 193 patients now and only $39M YE?
Preposterous! How does that spreadsheet work? Are we supposed to stop taking new patients at mid-year?
Here are the 4 abstracts for AACR April 8-10...
2083 Ponatinib potently inhibits the activity of mutant variants of FGFR commonly found in endometrial, lung and other cancers
Monday, Apr 08, 2013, 1:00 PM - 5:00 PM
2084 Ponatinib is a highly potent inhibitor of activated variants of RET found in MTC and NSCLC
Monday, Apr 08, 2013, 1:00 PM - 5:00 PM
3394 Ponatinib, a pan-BCR-ABL inhibitor, potently inhibits key activating and drug-resistant KIT mutants found in GIST
Tuesday, Apr 09, 2013, 8:00 AM -12:00 PM
5655 AP26113 possesses pan-inhibitory activity versus crizotinib-resistant ALK mutants and oncogenic ROS1 fusions
Wednesday, Apr 10, 2013, 8:00 AM -12:00 PM
And a special session...
Session Title: Target Validation by Chemical Probes/Designer Chemical Probes and Phenotypic Approach to Drug Discovery
Session Type: Major Symposium
Session Start/End Time: Tuesday, Apr 09, 2013, 8:15 AM -10:15 AM
[Timothy Clackson will describe strategies to target validated kinases with the right small molecules in a talk titled: “Design and development of ponatinib, a pan-BCR-ABL inhibitor for CML”.]
Link for those interested:
http://www.abstractsonline.com/Plan/AdvancedSearch.aspx
(search for Clackson in Author/Presenter Last Name)
Tomorrow is critical, not Tuesday...
The earnings call tomorrow at 8:30AM will be far more important than the RBC conference on Tuesday 9AM. When was the last time we heard anything original from the Dr. on an analyst call?
In order of potential for breaking news...science community first, then shareholders, then analysts.
No analyst appreciates how geeky/prudish HB is...
We always disappoint on earnings calls because Dr.B et al refuse to announce scientific progress at corporate events. Note Monday's agenda will cover "key corporate objectives...and corporate activities", like recent hires, EU headquarters, and plans for new Iclusig trials. Most other biotechs have no issue spinning progress updates and status reports on earnings calls to boost share price, something like "XYZ enrolls new patient in Phase 1b trial!"...
At best for '113 we will hear MTD has been reached and that new data will be presented at ASCO in May/June. We should hear Iclusig update with expected YE'13 sales raised, my guess is from $50M to $65-68M.
A long shot here...but I'm also hoping to hear pre-announcement on next molecule target and indication, with pre-clinical data to be presented at AACR in early April with IND to follow. '113 was introduced this way in 2010.
Use this link to compare net profit margins...
http://finviz.com/screener.ashx?v=161&f=ind_biotechnology&o=-netmargin
Most bios in transition to a commercial operation see 35-50% profit margin. But you will find established big bio in the 25%-30% range. I think long term we will do better than 25-30%, based on fewer drugs, best-in-class safety/efficacy, and clearly defined patient populations. In other words our drugs will comparatively sell themselves.
So I've assumed a descending net profit margin range from 50% in 2014 down to 35% by 2020.
By the way I assume total sales of $250M in 2014 and $5B (includes $2.4B Pona, $2.2B '113, and $400M XYZ) in 2020.
Follow up on Timmy C.'s fragment design for LDHA...
http://practicalfragments.blogspot.com/2013/02/fragment-linking-for-ldha-ariads-turn.html
Has '113 reached the DLT?
"Our oncologist has recommended LDK378 and possibly CHUGAI. He said Ariad's drug has had recent pulmonary toxicity problems? Has anyone heard this?" [2.15.13]
I would expect something like this to be the DLT. Isn't pneumonia or pneumonitis a form of pulmonary toxicity?
Don't forget Rachel McMinn lowered to $27M in Dec...
"...looking for slow initial Iclusig launch...We model $27M in 2013 US Iclusig sales, well below the company's soft guidance of <$50M and consensus of $49M. Our analysis shows consensus implies Iclusig outperforms the Tasigna US launch by 25%+"
Is Seeking Alpha guy serious about $11.40 for Iclueliss?
From article..."ARIA has stated that the mean duration of treatment associated with Ponatinib will be 3 years, on average patients will receive 6 months of treatment every year..."
Uh no...and no.
Projected sales modeled with 3 years of treatment is not the same as the mean duration. The mean duration in the PACE trial has not yet been reached. Also new patients receive 6 mos. of treatment in first year because they start in each of the 12 months of the year. After first year the model should include full 12 months of drug for all patients.
I think his NPV of $11.40 per share needs a major adjustment.
SEC link included...look under Disclosure and Recent Rule Changes
http://www.sec.gov/investor/pubs/analysts.htm
Doesn't mean HB has to be "quiet".
Now begins the 10-day quiet period...
NASDAQ and NYSE have a rule mandating a 10-day "quiet period" after a secondary (40 days for IPO), during which underwriters are restricted from issuing any earnings forecasts or research reports for the company.
Underwriter's have 30 days to purchase remaining over allotments.
I suspect all remaining shares will be purchased at $19.60 by Feb 24. At that point share price will be $25-26, assuming all of the below are included at Q4 earnings call on/about Feb. 8th:
1. Update launch and prescription count for Iclusig.
2. Update enrollment status of EPIC and earlier timeline for 12 mos data (May '14?)
3. Outline additional registration trials and timing for Iclusig in AML, GIST, and NSCLC.
4. Provide MTD and recommended dose for PH2 of '113.
5. Announce timing for IND of 5th molecule (just after ASCO)
With the exception of #5 aren't these overdue?
Neurodegenerative diseases too? C'mon....
Couldn't just stick with cancer huh, Willie? Frankie? Gotta tackle Alzheimer's and Parkinson's too? Well, I did read somewhere that the world population is aging, may be opportunity here.
http://worldwide.espacenet.com/publicationDetails/biblio?DB=worldwide.espacenet.com&II=4&ND=3&adjacent=true&locale=en_EP&FT=D&date=20121011&CC=WO&NR=2012139027A1&KC=A1
World patent pending. Interesting that this is the only pending patent application that shows up on Espacenet, but not on USPTO.
Other recent US patent applications include:
Jan. 17, 2013 - Acetylenic Heteroaryl Compounds
Jan. 3, 2013 - Monocyclic Heteroaryl Compounds
Dec. 13, 2012 - Methods and Compositions for Treating Cancer (Ponatinib)
Dec. 13, 2012 - Compounds for Inhibiting Cell Proliferation in EGFR-Driven Cancers
http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=0&f=S&l=50&TERM1=ariad&FIELD1=AS&co1=AND&TERM2=&FIELD2=&d=PG01
Found this tidbit from Jan. 9 on SciBite from Timmy C., et al. I tried running this through Google translator but apparently it's already in English (kkk). Could LDHA inhibitor be the next molecule? Also first specific mention of fragment-based drug discovery from HB's clan that I can recall.
http://www.ncbi.nlm.nih.gov/pubmed/23302067
J Med Chem. 2013 Jan 9. [Epub ahead of print]
Fragment Growing and Linking Lead to Novel Nanomolar Lactate Dehydrogenase Inhibitors.
Kohlmann A, Zech SG, Li F, Zhou T, Squillace RM, Commodore L, Greenfield MT, Lu X, Miller DP, Huang WS, Qi J, Thomas RM, Wang Y, Zhang S, Dodd R, Liu S, Xu R, Xu Y, Miret JJ, Rivera V, Clackson T, Shakespeare WC, Zhu X, Dalgarno DC.
Source
ARIAD Pharmaceuticals, Inc. , 26 Landsdowne Street, Cambridge, Massachusetts 02139, United States.
Abstract
Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway. Cancer cells rely heavily on glycolysis instead of oxidative phosphorylation to generate ATP, a phenomenon known as the Warburg effect. The inhibition of LDH-A by small molecules is therefore of interest for potential cancer treatments. We describe the identification and optimization of LDH-A inhibitors by fragment-based drug discovery. We applied ligand based NMR screening to identify low affinity fragments binding to LDH-A. The dissociation constants (K(d)) and enzyme inhibition (IC(50)) of fragment hits were measured by surface plasmon resonance (SPR) and enzyme assays, respectively. The binding modes of selected fragments were investigated by X-ray crystallography. Fragment growing and linking, followed by chemical optimization, resulted in nanomolar LDH-A inhibitors that demonstrated stoichiometric binding to LDH-A. Selected molecules inhibited lactate production in cells, suggesting target-specific inhibition in cancer cell lines.
An alternative way model sales is start with the 2,500 R/I pts. switching TKI in 2013 in US.
1). Assume 20% are T351 - 500 pts.
2). Assume half of remaining are R/I to one TKI only, and we get 15% - 150 pts.
3) Leaves other half as R/I to 2 or more TKI's, and we get 75% - 750 pts.
4) Add 100 from US expanded access (slide shows 179 US pts.)
Total is 1500 pts. at year end.
As to discontinuation, I think for 2013 the number will be low due to half starting second half of year. I would estimate 35% terminate from July to Dec., 750 pts. x 35% = 262 pts.
So this would drop year end total to 1240 pts. which would lower total revs. from $79 to $68M.
Increasing Iclusig '13 rev. est. to $79M
Based on higher attrition of 400+ compassionate/expanded access/off label patients.
Here's how (yes I made a spreadsheet):
1Q $4.3M (approx. 300 new pts. for 1.5 mos. avg.)
2Q $13.7M (addl. 350 new pts. 1.5 mos. plus 1Q pts. for 3 addl. mos.)
3Q $24.5M (addl. 400 new pts. for 1.5 mos. plus 1-2Q pts. for addl. 3 mos.)
4Q $36.7M (addl. 450 new pts. for 1.5 mos. plus 1-3Q pts. for addl. 3 mos.)
Total $79M with 1500 pts. rolling into 2014.
Continue this pace of prior qtr. + 50 new pts. and YE '14 revenue will be $200M.
Note revs. for 1st qtr. are $4.3M....please adjust your expectations accordingly.
Can you really look at this chart and doubt our future?
http://www.mycancergenome.org/content/other/molecular-medicine/targeted-therapeutics
Ariad has demonstrated activity in 11 of the 30 or so families of proven targets for tyrosine kinase inhibitors, and with only 3 molecules to boot, each targeting several indications.
All we need to round out the sweet would be a Her-2, Jak, PI3k, or VEGF target. Anyone care to venture a guess for the next molecule's target?