Hot Watch List (comments).
EMIS.OB (speculative buy)
Everybody is dreaming about this investment scenario: buy some biotech for $1 and after couple months suddenly see pps $10 or even more i.e. >1000% gain. Usually it's happen after very successful phase III trial or unexpected FDA approval of previously rejected drug (VNDA).
Sure that all biotech investors keep these potentially explosive stocks on radar. But what about hidden ones?
Look at EMIS.OB. It's almost dead biotech: without any R&D, recently terminated CEO (already second or even third?), recent bad news that EMIS oral delivery technology of peptide/protein drugs is not so good ("Novartis informed Emisphere that, although the study confirmed that oral PTH1-34 was both safe and well-tolerated, several clinical endpoints were not met. Based on the data analyzed, Novartis has terminated the study and anticipates no further work on the oral formulation of PTH1-34")...
So, pps is $1 and no hope? They had money before end of June so dilution is imminent.
May be... May be not...
Look at this trial:
A Study to Evaluate Oral Salmon Calcitonin in the Treatment of Osteoporosis in Postmenopausal Women Taking Calcium and Vitamin D
Purpose
The purpose of this Phase III study is to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of patients with osteoporosis
Condition Intervention Phase
Osteoporosis
Drug: SMC021 Oral calcitonin
Phase III
Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Multi-Center, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Salmon Calcitonin in the Treatment of Osteoporosis in Postmenopausal Women Taking Calcium and Vitamin D
Further study details as provided by Nordic Bioscience A/S:
Primary Outcome Measures:
Number of patients with new vertebral fractures [ Time Frame: December 2011 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
Number of patients with non-vertebral fractures [ Time Frame: December 2011 ] [ Designated as safety issue: No ]
Estimated Enrollment: 4500
Study Start Date: March 2007
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
This drug has a billion sale potential. But you will ask what EMIS will have from it?
Well, just 10% of royalties i.e. $100M per year during next 15-17 years. Because this SMC021 Oral calcitonin is based exclusively on EMIS oral delivery technology: just tablets containing 0.8 mg salmon calcitonin + EMIS carrier 5-CNAC disodium salt monohydrate.
So, welcome to biotech gambling: buy at $1 now and have >1000% or nothing in August/December 2011.
What is the probability to have >1000%? Nobody knows definitely.
Trial Primary Outcome Measures:
Number of patients with new vertebral fractures [ Time Frame: December 2011 ] [ Designated as safety issue: No ]
I.e. if oral calcitonin group have less vertebral fractures we will have a billion blockbuster drug here and EMIS pps >$10 in one day. If no difference: EMIS crashed completely and goes to bankruptcy i.e. pps <$0.10
>1000% gain vs. 900% losses... Almost Vegas...
But for example you have $100 invested in EMIS now. After positive trial you will have $1000. In case of crash you will lose $90.
So, what is the probability of success for trial and for EMIS?
My number is >70% of success i.e. drug meet primary (and may be secondary) measures. Again this prediction is based only on my scientific analysis of EMIS technology. May be later I will explain it in this comment.
Disclosure: I don't have EMIS positions now.
June 27, 2011 by BiotechInvest
Don't forget about EMIS financial situation. It's not good actually:
"The Company estimates its annual cash burn rate to support continuing operations without implementing additional cost reductions is approximately $8 million per year. Consequently, the Company anticipates that its existing capital resources, without implementing cost reductions, raising additional capital, or obtaining substantial cash inflows, will enable us to continue operations through approximately June 2011, or earlier, if unforeseen events arise that negatively affect our liquidity. Management believes there are reasonable alternatives potentially available to the Company that will enable it to meet its near term operating cash requirements, but there are no assurances that such financing can be obtained on favorable terms or at all. Please refer to the Quarterly Report on Form 10-Q for the quarter ended March 31, 2011 for additional information."
They can do some stock dilution (may be $5-6M). The investors usually don't like so pps may drop to $0.7-0.8 per share
Since it's already end of June may be tomorrow we will see some news...
Lowest entry point will cut the potential losses if NOV osteoporosis drug based on EMIS eligen technology show nothing in phase III trial. So, it's everything or nothing scenario for EMIS and for EMIS gamblers.
July 30, 2011 by BiotechInvest
I got several questions about my 70% probability prediction for oral salmon calcitonin trial (drug is based on EMIS technology and EMIS will get double digits royalties from sales).
So, what is this drug? In simple words it's a mixture of peptide salmon calcitonin 0.8 mg and Emisphere carrier 5-CNAC (150-200 mg). The bioavailability of this formulation is very low: 0.5-1.4%. But the mean bioavailability of Calcitonin-Salmon Nasal Spray (approved by FDA for OP) is approximately 3% of that of injectable calcitonin in normal subjects i.e. single intranasal (IN) spray of 200IU will delivered only 6 IU of sCT.
Since 0.8 mg = 4800IU and tablet BA= 0.5-1.4% one tablet will delivered 40-80 IU of salmon calcitonin daily i.e 10 times more than IN formulation.
What is the efficacy of IN spray of sCT?
A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group.
PURPOSE: We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis.
SUBJECTS AND METHODS: A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group.
RESULTS: During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1. 5%, P<0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P<0.01) as compared with placebo.
CONCLUSION: Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.
After approval of IN sCT the sales were:
2005 - $365M
2008 - $112M
Why so big drop of sales? There is very simple explanation: very inconvinient pathway of delivery. IN spray is very unpleasant substance and often induces numerous symptoms of nose: nasal crusts, dryness, redness or erythema, nasal sores, irritation, itching, thick feeling, soreness, pallor, infection, stenosis, runny/block ed, small wound, bleeding wound, tenderness, uncomfortable feeling and sore across bridge of nose.
Oral sCT tablets have no any side effects, may be just some bitter taste in mouth...
So, oral sCT tablets should be more effective than IN formulation i.e. reduce the risk of new vertebral fractures by >33% compared with placebo and in such way the Oral sCT annual sales should be >>$365M. Doctors will prescribe this drug like a vertebral fracture preventive medicine and $1B annual sales are easy possible for this drug.
Disclosure: I have a position in EMIS, may be will increase it twice if entry price is good (<$0.9). This stock is high risk and very high reward one. So, it's better to invest no more than $10k in it and at lowest entry price. Big money will not do it because their analysts can't predict oral sCT success. But were they right about DNDN?
September 06, 2011 by BiotechInvest
It's already September and no news for EMIS... They promised "Estimated Primary Completion Date: August 2011"
But Estimated Study Completion Date was December 2011...
Now it's:
Estimated Enrollment: 4500
Study Start Date: March 2007
Estimated Study Completion Date: November 2011
Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
The question is why they (Novartis and Nordic Bioscience A/S) changed the date? Usually they send all blind trial data to some independent statistics company and after this they have an approximate date for trial result release. 4500 patients data need a couple months... i.e. November if start statistics in August.
So, let us wait for EMIS resurrection in November... or "sudden death"...
October 17, 2011 by BiotechInvest
EMIS investment was always funny and ... tricky , especially now. Somebody tricked EMIS gamblers and now he is accumulating their shares likely to a vacuum cleaner.
EMIS gamblers were mostly scared by old known news i.e. oral salmon calcitonine is useless againts osteoarthritis (OA):
"CEDAR KNOLLS, N.J., Oct. 13, 2011 (GLOBE NEWSWIRE) -- On July 23, 2010 Emisphere Technologies, Inc. (OTCBB:EMIS.OB - News) reported that Novartis Pharma AG ("Novartis") and its license partner Nordic Bioscience A/S ("Nordic Bioscience") provided certain information in connection with their Phase III Study 2302 assessing the safety and efficacy of oral calcitonin ("oCT") in the treatment of osteoarthritis of the knee. Study 2302, along with its companion Study 2301, incorporates Emisphere's unique and proprietary Eligen(R) Drug Delivery Technology for the improved oral absorption of salmon calcitonin. Specifically, in July 2010, Novartis informed Emisphere that an independent Data Monitoring Committee ("DMC") conducted a futility analysis of one-year data for all patients enrolled in Study 2302, including assessments of safety and efficacy parameters. Although the DMC concluded that there was no reason to stop Study 2302 because of safety concerns, there was no reason to continue the study for efficacy. Novartis has informed Emisphere that because of a previously more encouraging futility analysis of Study 2301 (reported by us on Dec 9th, 2009), Novartis and Nordic Bioscience had decided to continue the study to be able to pool results and compare safety information.
Following completion of Study 2302, Novartis has recently informed Emisphere that it has reviewed the first interpretable results and has advised Emisphere of its top line conclusions as follows: Preliminary analysis of two year study data showed both co-primary endpoints and secondary endpoints of the study were not met. Additionally, preliminary analysis of Study 2302 data showed a positive safety profile."
What?! EMIS technology is not effective? Sell EMIS now! (it's not my call)
Is it true? Nope. Complete b..sh..t
oCT was never even a potential drug for OA. Just simple story here: some idiot at NVS was thinking that it could be interesting to try oCT against OA. Based on what? Please, don't ask me... I have only unprintable words for explanation of this stupidity.
"Additionally, a Phase III study of oral calcitonin in osteoporosis has been completed and first interpretable results are expected in the fourth quarter of 2011."
OA and OP
Just read this sourse:
"Basics of osteoarthritis (OA)
Osteoarthritis, or degenerative joint disease (DJD), is a form of arthritis characterized by the loss of joint smoothness and range of motion without major joint inflammation.
Facts and myths
Fact: Low bone density is not associated with osteoarthritis
Bone density is actually HIGHER, rather than LOWER, in osteoarthritis. Low bone density is the telltale sign of osteoporosis, a skeletal disorder characterized by weakened bones due to excessive loss of bone mass.
Osteoarthritis, on the other hand, is characterized by increased bone density and bony growths (osteophytes) in conjunction with articular cartilage degeneration.
Osteoporosis and osteoarthritis are two different diseases with opposite bone density problems.
Fact: Drinking milk cannot prevent osteoarthritis
Milk is an excellent source for calcium, which is important for bone formation.
However, a low calcium diet is known to increase one's chance of getting osteoporosis, not osteoarthritis.
Calcium intake is not directly associated with the onset of osteoarthritis. Vitamins A, C, and, E, the major antioxidants, have been identified as having a potential for protecting cartilage and connective tissue from oxygen radical damage. Vitamin D may also play an important role in osteoarthritis by way of bone mineralization and cell differentiation. Good dietary practices may help protect individuals against osteoarthritis to some extent.
Fact: Osteoarthritis does not cause bone erosion.
Osteoarthritis does not cause bone loss or fractures. On the contrary, it is associated with increased bone density and abnormal growths (osteophytes) due to the deficiency in bone resorption.
Weak, porous bone structures due to low bone density is the signature symptom of osteoporosis, a different and separate disease. "
Will you use oCT for OA when you know these facts?
Disclosure:I have EMIS positions and will wait for OP phase III trial release in Q4 2011.
10/27/2011 by BiotechInvestIt seems like that EMIS gamblers are really scared by these "no news" from EMISWell, I'm not...Here are some recent achievments in OP area:Amgen has reported on two clinical trials designed and funded by the company:
• In a phase 3 clinical trial ('FREEDOM') involving 7,808 women, aged 60 to 90, there were significant improvements in the subset of women with more severe disease at the beginning of the study (two or more prevalent vertebral fractures and/or one or more prevalent vertebral fractures with moderate or severe deformity). Researchers reported a 35% risk reduction with denosumab compared with placebo (17% vs. 49%), with new vertebral fractures in this subset of only 31% for those taking denosumab, versus 71% receiving the placebo.
• The second phase 3 clinical trial involved 1,468 prostate cancer patients receiving hormone-deprivation therapy, who were randomised to receive either denosumab or a placebo every 6 months over a 36 month period. All patients also received supplemental calcium and vitamin D. Of those taking the placebo, 3.9% experienced bone fractures during the 36 months, compared with 1.5% of those who received denosumab.
Both studies showed a decrease of fractures comparable to zoledronic acid and teriparatide, and slightly more than under oral nitrogenous bisphosphonates.
On 13 August 2009, an Amgen press release regarding the meeting that day with the Advisory Committee for Reproductive Health Drugs (ACRHD) of the (FDA), to review the potential uses of Prolia, said:
After reviewing safety and efficacy data from 30 clinical studies involving more than 12,000 patients, the Committee recommended approval of Prolia for the treatment of postmenopausal osteoporosis, and for the treatment of bone loss in patients undergoing hormone ablation for prostate cancer.
June 2010: Denosumab was approved for postmenopausal osteoporosis by the US FDA on June 2, 2010.
Common side effects include osteonecrosis of the jaw, back pain, pain in the extremities, musculoskeletal pain, high cholesterol levels, and urinary bladder infections.
November 2010: FDA approved denosumab (to be marketed as Xgeva) for the prevention of skeletal-related events in patients with bone metastases from solid tumors. (Dosing is a 60 mg subcutaneous injection every six months for postmenopausal osteoporosis and 120 mg every 4 weeks for patients with solid tumors).
The Committee for Medicinal Products for Human Use (CHMP) issued a Positive Opinion for denosumab on 17 December 2009, for the treatment of postmenopausal osteoporosis in women and for the treatment of bone loss in men with hormone ablation for prostate cancer. Denosumab was approved for marketing by the European Commission on May 28, 2010.
Prolia will cost $825 per 60 mg injection (based on "wholesale acquisition cost" or WAC). Prolia's price is competitive with other branded osteoporosis therapies while reflecting its positive clinical profile for patients at high risk for fracture.
Every six month 60 mg subcutaneous injection administered by a health care professional i.e.$1,650 per year
In September 2009, the firm Sanford Bernstein projected that annual worldwide sales of the drug would reach $5 billion in the year 2015. It projected 2010 sales of over $650 million, mostly from use as a twice-yearly injectable for osteoporosis treatment in post-menopausal women over 50.So, if oral sCT reduce 35% the new vertebral fractures risk compared with placebo it will have at least 50% of this $5 billion in the year 2015. 8-9% EMIS royalties in oral sCT sales give us $450M per year. Any biotech with $450M sales per year have cap at least $1B i.e. EMIS pps should be >$12$1,650 per year = 1 tablet price for oral sCT = $4.5 and it's real And sCT has not such "side effects that include osteonecrosis of the jaw, back pain, pain in the extremities, musculoskeletal pain, high cholesterol levels, and urinary bladder infections" may be just some bitter taste in mouth...
October 31, 2011 by BiotechInvest
So, tomorrow we will have a November and the Estimated Study Completion Date: November 2011
EMIS gambling is very close to final and gamblers are discussing all possible pitfalls: sCT developed Abs, SNAC patents (actually SNAC is not a carrier in sCT pills because NVS uses EMIS carrier 5-CNAC) and etcetera.
And almost nobody was worry about these results from IN sCT:
"The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03).
The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo."
One can say that if NVS sCT tablets deliver more sCT than this intranasal 400-IU dose we will have an arm that is not significantly different from placebo i.e. primary Primary Outcome Measures (Number of patients with new vertebral fractures) in treated arm will not be significantly different from placebo"
Since, NVS is testing only one dosing (0.8 mg sCT) they don't have any window here. If high sCT Cmax is bad these tablets will be worse than placebo.
Thus, phase III trial results release become a too risky event even for gambling.
But I will analyse the probability of this possible result: "oral sCT tablets are "not significantly different from placebo".
The simple calculations said:
The mean bioavailability of Calcitonin-Salmon Nasal Spray (approved by FDA for OP) is approximately 3% of that of injectable calcitonin in normal subjects i.e. single intranasal (IN) spray of 200IU will deliver only 6 IU of sCT.
And 400IU will deliver only 12 IU of sCT.
Even if the bioavailability of NVS formulation (0.8 mg and Emisphere carrier 5-CNAC 150-200 mg) is very low: 0.5-1.4%.one tablet will delivered 40-80 IU of salmon calcitonin daily
i.e NVS oral sCT will deliver 10 times more sCT in patient blood than 200IU IN formulation and 5 times more than 400 IU IN dose.
but 400 IU IN is "already not significantly different from placebo"
Logic say: sell EMIS now, have a gain and forget about it.
But science asks: is it really true that higher dose of sCT could be worse than low dose?
First question: did they really measure IN sCT PK in this trial?
Indeed, if you show that higher Cmax of sCT is worse than lower NVS tablets that deliver 40-80 IU of sCT daily will be doomed.
But what if IN 400 IU dose delivers less than 200 IU dose? How it's possible?
Intranasal delivery is complicate pathway and sCT is not a neutral peptide for nasal mucosa:
Front Biosci. 2006 Sep 1;11:2035-44.
Effect of pH-variation on insertion and ion channel formation of human calcitonin into planar lipid bilayers.
Micelli S, Meleleo D, Picciarelli V, Gallucci E.
SourceDept. Farmaco-Biologico, Università degli Studi di Bari, I-70126 Bari, Italy.
Abstract
Human calcitonin is the physiological hormone involved in calcium-phosphorus homeostasis. However, its use is limited by its propensity to form aggregates. We find that the type of host lipid has a pronounced influence on human calcitonin fibrillation or incorporation, as assessed by channel formation, in planar lipid membranes at neutral pH. At pH 7, human calcitonin is able to interact and form channels with negatively charged dioleoyl-phosphatidylglycerol (DOPG) bilayers and with zwitterionic palmitoyl-oleoyl phosphatidylcholine (POPC) bilayers containing 15% negatively-charged DOPG, but not with POPC bilayers. At low pH (4.5 and 3.8), the conformational variation of the peptide enables it to insert into POPC and POPC:DOPG but not into DOPG bilayers. The model proposed for human calcitonin interaction and channel formation at acidic pH was based on theoretical predictions of the protonation-deprotonation state of some amino acids, in particular in the fibrillating sequence of peptide molecules; the length of the alpha-helix, and the electrostatic and/or hydrophobic interaction also seem to be relevant. These results may suggest that human calcitonin at low local pH could be involved in osteoclasts' calcium-sensitive permeability through channel formation and/or receptor interaction."
Thus, the high concentrations of intranasal sCT may interfere with drug bioavailability i.e. sCT itself may induce these numerous symptoms of nose: nasal crusts, dryness, redness or erythema, nasal sores, irritation, itching, thick feeling, soreness, pallor, infection, stenosis, runny/block ed, small wound, bleeding wound, tenderness, uncomfortable feeling and sore across bridge of nose.
So, the nasal mucosal inflammation induced by high sCT may decrease the bioavailability of 400 IU IN dose.
And 40-80 IU of salmon calcitonin daily delivered by tablets will be significantly different from placebo i.e. it will "significantly reduced the risk of new vertebral fractures by 33% (or more) compared with placebo"
Conclusions: I'll keep my 15k EMIS shares and wait for trial results release. Gambling is gambling. Actually whole gamling strategy is based on simple rule: everybody thinks that he is smarter than others. But I will not buy 150k EMIS shares because I know that I'm not smarter than other biotech investors. If NVS trial fail EMIS pps will be $0.16 i.e. 90% losses for this stock but it will be less than 5% losses for my entire portfolio (I always recommend to use this <5% losses rule for biotech investment).
11.14.11 by BiotechInvest
Well, it seems like that high dose of sCT is not good. NVS tablets delivered 40-80 IU of sCT and treated arm was not significantly different from placebo. More drug delivered ≠ better results. May be if they decrease sCT in tablets at least 10 times (to 0.08 mg) they will have a correct blood concentration of drug.
Any way EMIS is a dead company now.
BTW I hope that any my subscribers didn't have any losses with EMIS. I did next trades with EMIS:
6/30/2011 bought EMIS 10000 $0.91
8/4/2011 bought EMIS 5000 $0.83
9/30/2011 sold EMIS 7500 $1.84
10/6/2011 sold EMIS 7500 $1.65
gain: +$12,900
10/14/2011 bought EMIS 15000 $1.23
11/14/2011 sold EMIS 15000 $0.45
losses: -$11,700
It was really nice gambling but if EMIS pps drops to$0.16 (as I predicted if OP phase III trial failed) the losses
could be -$16,000
But some crazy gamblers continue to buy EMIS even now. Well, they will do it even at $0.16 and at $0.016...
It big mistery for me why someone is buying "biotech garbage" but they help us to avoid big losses with failed biotechs.