Celsion Corporation (CLSN)

[GD]

I am very bullish with CLSN, I constantly adding to my
huge position even yesterday, I believe CLSN is going to
repeat CPXX's success, known and efficacy proven drugs,
CPXX's in different formulation, CLSN's in different delivery
system. CPXX's PIII is outperforming limited PII data,
and I blieve OPTIMA may outperform HEAT subgroup data
because I am assuming CLSN is smart to learn details of
HEAT subgroup data and enroll HCC patients who may benefit
even more from Thermodox. I am betting first look stop for
efficay next week, I may be very wrong but I put huge money
in my believing in CLSN. Let's see what comes next week!

[stockweiser]

You still bullish on CLSN?

[GD]

CEO is not totally honest, the Q rate of $4m cash burn is
for now, once the Gen-1 PII trial enrollment ramps up
fast if the blinded 12 patient data early next year are
very promising, we may see cash burn run up fast too next
year, IMO. By the way, CLSN is selling 1+M shares/Q now,
constantly raising cash which is the reason CLSN is at
$1.7/share, if stree believes CLSN has cash to run up to
early 2021 and not selling shares constantly, CLSN may
be trading at $2.5 to $3 now, IMO. Another biotech I
am watching OMER is in the same place constantly short
of cash, OMER's CEO is playing games with street and think
he can win the funding battle, he is very wrong, no
small biotech short of cash can win with street, soon
or late, CLSN and OMER have pay the dues to the street
for money, the new deal with 100K free shares to Aspire
is the price CLSN is paying Aspire for future $10M funding
to cover second look if needed, IMO.

[stockweiser]

I don't get that though they said they have cash till 2021.

[GD]

I think Aspire demand to rewrite the $10M remain from last year's
agreement for compensation Aspire bought millions of shares above
$1.80, CLSN needs the $10M to give them room to raise money to
avoid going concern if OPTIMA needs second look, IMO.

[stockweiser]

What is your take on the Aspire deal?

[GD]

I think I wrote my opinions here on many posts, it just
makes scientific sense Thermodox is working to kill the
distant small HCC tumors RFA can not do, if we believe
Thermodox work, then OPTIMA should repeat the subgroup
results, since HR is almost constant after enough events
and KM curve separation, first look HR is the final HR
which should be 0.65 or less, that is the reason I place
a high chance of stop for efficacy.

[Biobonic]

True that on DD

Tell, why do you believe that efficacy is a possibility? And what is the percent chance of that?

? Are there enough enrollees with enough time in the trial to make a solid measurement and see a differentiation between the two groups?

This is what I have so far: Dug thru a few annual reports.

The first trial did not meet the primary endpoints.

In follow up some things came to light:

Perhaps the Thermodox was not heated to the correct temp.

Perhaps the dwell time of the Thermodox in the tumor was insufficient.

The overall survival (years past the end of the trial) of the Thermodox treated group is very impressive.

So Celsion basically restructured the trial with the findings from the first trial.

[GD]

Not much time to do DD, we may read the first look
decision PR to continue or stop for efficacy by next
Monday or Tuesday, to continue, 20% down side risk? To
stop for efficay, $12 to $15 price target, IMO. Now
I understand why CLSN chooses HR as target, not P value
the normal trial value designed for interim efficacy,
for best chance to stop for efficacy if OPTIMA is to
repeat the subgroup OS KM curves, IMO. I am betting
stop for efficacy next week, good luck!

[Biobonic]

[Biobonic]

When deciding on treatment, health care providers consider the cause and severity of the neutropenia. Mild cases may not need any treatment.

Other cases can be life threatening.

No estimates of efficacy, but the longer a trial progresses the better the difference between the two groups.

Q2 2019 Results - Earnings Call Transcript
While it is possible for OPTIMA study to be declared successful at the first interim, the probability of success improves with the number of patients evaluated. While we remain optimistic for a positive trial reserved in October the likelihood of success is much greater at the second interim analysis, which is expected to occur in the first half of 2020 assuming the current rate of death that we're seeing in the trial population.

Just coming up to speed on Celsion.

[GD]

From the HEAT data, we can see 46% patients has neutropenia,
if CLSN has the blinded safety data, CLSN can do a very good estimates
of OS data, IMO. Do you have any estimates of chances stop for
efficacy at first look?

[Biobonic]

Here is some additional info on side effects.

More here
Findings
Between March 13, 2015, and March 27, 2017, ten patients were enrolled in the study (six patients in part I and four in part II), and received a dose of LTLD followed by focused ultrasound exposure. The treatment resulted in an average increase of 3·7 times in intratumoural biopsy doxorubicin concentrations, from an estimate of 2·34 µg/g (SD 0·93) immediately after drug infusion to 8·56 µg/g (5·69) after focused ultrasound. Increases of two to ten times were observed in seven (70%) of ten patients, satisfying the primary endpoint. Serious adverse events registered were expected grade 4 transient neutropenia in five patients and prolonged hospital stay due to unexpected grade 1 confusion in one patient. Grade 3–4 adverse events recorded were neutropenia (grade 3 in one patient and grade 4 in five patients), and grade 3 anaemia in one patient. No treatment-related deaths occurred.

[GD]

I mean side effects which are strongly relate to chemotherapy drug,
see page 21 for RFA+Thermodox side effects:

http://investor.celsion.com/static-files/1da10860-7a91-4110-9fdc-2878c390f1a5

[stockweiser]

Thermodex arm has strong side effects?

[GD]

By the way, I firmly believe CLSN has a very good idea
how OPTIMA trial is going, they can estimate OS ratio
from the 128 events from their side effects, patients
on Thermodox arm have strong chemotherapy drug side effects
and placebo arm patient do not. Reading tea leaves from
CEO comments:

"The bottom line was we enrolled almost 100 patients in Vietnam in a relatively short period of time. Of which some of the most enthusiastic investigators we went back just a month ago, Dr. Boris and I, to thank the investigators for all their work to review with them the case studies to get their impressions of where we stood with radiofrequency ablation and thermal docks. Just impressions because it's a blinded study, they're all overwhelmingly positive with the trial and the outcome and their patients' recovery and progress."

[GD]

I did, many times. He recommends IV Thermodox after the
tumor is heated to 40+ C. But with the 45+ minutes RFA,
the pig experiment proves liver has enough Dox to kill
the very small tumors, CLSN should know and IV more
than enough Thermodox to compensate some of loss from
leakage, IMO.

[stockweiser]

Did you watch YouTube video of inventor of Thermadox on his comments of HEAT trial?

[GD]

I am willing to believe Prof. Lencioni statement indicates his very
positive opinion of OPTIMA trial results:

“ThermoDox® is being studied as the first potential curative treatment for HCC in a large, randomized, multicenter Phase III trial,” said Prof. Lencioni. “Post-hoc analyses of the Company’s first Phase III study of ThermoDox® – the HEAT Study – generated important findings that demonstrated its potential to significantly increase overall survival when target tissue is adequately heated with RFA for 45 minutes or longer. The Company’s ongoing second Phase III study, the OPTIMA Study, is designed to test this survival benefit hypothesis. If this hypothesis bears out in the OPTIMA Study, ThermoDox® will be the first and only FDA approved drug for the treatment of HCC with curative intent.”

[stockweiser]

Find out in about 6 weeks

[GD]

Look at page 20 on the subgroup >45 minutes KM curves,
there are 54 from RFA+Thomdox + 73 RFA =127 events,
if We see a slightly better KM curves from interim
look with 128 events, we may have the trial results
stopped for efficacy next month, I am betting we may
get that results because the OPTIMA PFS is tracking better
than the subgroup data, should translate into better OS
results in the OPTIMA, IMO.

http://investor.celsion.com/static-files/1da10860-7a91-4110-9fdc-2878c390f1a5

[stockweiser]

Thanks for that informal response I look forward to reading more of your commentaries in the future.

[GD]

ON Q4 and Q1 CC, CEO said less than 50% chance of stop for efficacy,
but on Q2 CC, he was more than neutral. From my reading of his comments on Q2
CC, the underline message is very bullish for first look stop, I have
never heard a company provide interim look stop conditioning on HR,
always on a P value like less than 0.01 or 0.001, HR and P value are
related, but not like what He says. Now we know the first look stop for
efficacy P is less than 0.02. For example, We may have HR 0.66, but
the P value may be 0.01, in this case, OPTIMA may stop for efficacy,
this means 99% the HR 0.66 is real compare to the OPTIMA design of HR
0.75, median OS advantage 33% and 80% power at 197 events.

Here is example of interim stop HR and P value with trial assumptions:

Median overall survival was 35.3 months (95% CI, 32.2-NR) for patients receiving XTANDI + LHRH therapy* vs 31.3 months (95% CI, 28.8-34.2) for those receiving placebo + LHRH therapy* (HR = 0.77 [95% CI, 0.67-0.88])

At a prespecified interim analysis for overall survival, XTANDI significantly reduced the risk of death by 29% in patients who received XTANDI + LHRH therapy* vs placebo + LHRH therapy* (HR = 0.71 [95% CI, 0.60-0.84]; P < 0.0001)

https://www.xtandihcp.com/mcrpc-results/primary-endpoints-prevail-trial

The PREVAIL trial was stopped for efficacy on the interim look with above data, OS advantage of 4 months, 35.3 vs 31.3 months, and HR 0.71
risk of death by 29% , but P value less than 0.0001.

By the way, yesterday, Slingshot Insights had a Expert Interview,
we may have someone talking about what the expert DR thinking on
the OPTIMA results next week after the listeners finishing their
positions, IMO. I am expecting very bullish talk from the DR:

https://slingshotinsights.com/projects/1114#

Bewarned: all my uneducated guess on OPTIMA first look stop chances!!!

[stockweiser]

I thought first look was less than 50%?

[GD]

The first look P value to stop for efficacy is less than 0.02,
first interim look for efficacy stop has a very good chance of
75%, IMO, HR is related to P value, but not as simple as CEO's
comments of median OS.

[GD]

Do you have any idea what is the P values for first HR=0.61 and second look
HR=0.7 to stop the trial? This is first time I hear a company provide HR for
stopping at interim look, I always hear P value for stopping the trial
like 0.01, 0.001 or less.

[veni vidi vici]

Thanks for catching it. You are absolutely correct.

I was simply looking at some of the statements from Tardugno that he repeatedly made in past earnings calls.

For example, here is how he explains the interim data readout OPTIMA hazard ratios on the Q4 2018 earnings call (dated 3/29/19) in response to a question by Matthew Cross of Jones Trading:

Matthew Cross
No, I think that does, appreciate that. And then, since this first interim data readout for OPTIMA is likely to be a major part of the story for 2019, could you kind of remind us of that optionality that I think you've kind of alluded to a little bit here, subsequent to this first look, and even for the second, next year before final data, in terms of what modifications you may be able to make if the lesser PFS for either arm or negatively outside of what you're anticipating, but more asking also about the potential to stop the trial earlier is a substantial enough survival benefit. I guess, this 33% specifically is shown sooner.

Michael Tardugno
Yeah. So the hazard ratio at the first interim, in order for us to be successful as 0.61. At the second interim, I believe it's 0.70. And at the third interim, that's 0.75. So if we want to talk in layman's terms, 0.75 translates to a 33% improvement, 0.70 represents a 42% improvement and 0.61 approximately 60 plus percent improvement in the way the statisticians talk about in the risk for death.

Source: https://seekingalpha.com/article/4251843-celsion-corporation-clsn-ceo-michael-tardugno-q4-2018-results-earnings-call-transcript

The correct numbers are:
HR of 0.75 = 25% risk reduction
HR of 0.70 = 30% risk reduction
HR of 0.61 = 39% risk reduction

[GD]

You are wrong of 64% reduction in risk of death of HR 0.61,
correct math is 39% reduction in risk of death.

[harry crumb]

Wow, haven’t been here in ages. Covered awhile back. Could this hit $1? Hhhhmmmm

[veni vidi vici]

Some reasons to remain "caveat emptor" on the stock...

- Despite the most recent change back to an excessive stock "pumping" tone, Tardugno in previous CCs repeatedly admitted it is highly unlikely that the phase 3 OPTIMA trial will be successful (i.e., show a hazard ratio of 0.61 which equals about a 64% reduction in risk of death) at the first interim analysis.

- For those not familiar with the Company, historically Tardugno used the same unwarranted pumping style leading into the previous phase 3 HEAT trial announcement before acknowledging in the end that the study outcome results were "not even close."

- Independently of the story management continues to sell, it is refreshing to be able to obtain the independent perspectives of Dr. David Needham, the inventor of the technology used in CLSN's DIGNITY / HEAT / OPTIMA studies. He correctly has been very critical of the study protocol designs that were adopted for CLSN's clinical trials. To learn more about his expert perspectives, his talk (specifically from minutes 16 through 23) at the European Foundation of Clinical Nanomedicine from a few years ago is enlightening. Here is the link:

[Antti]

Some further comments from the latest conference calls regarding China.

Q4 CC

Question:

I thought in the past year or so, I had heard there was a possibility that ThermoDox might have an early approval in China.

Answer:

With regards to China, I think I mentioned that Dr. Borys had a meeting with the Associate Director, Assistant Director of CDE. And again, I characterize it as impatient. This is an overwhelming problem in China. When we go to the hospitals that treat patients with HCC, it's incredible. You can't get through the hallway. There's just so many people. It’s such a great idea. They did, as I mentioned earlier, they did ask us to explore some alternate endpoints. Nick and some of our KOLs are discussing that as we speak. We think there may be an opportunity to present something later this spring before the summer to the CFDA and it could have a meaningful opportunity for the market and for the company.

Q1 CC

Question:

But it relates to regulatory approval in China. Is there a potential path for premarket authorization or basically market -- bringing ThermoDox to market in China in the Chinese market prior to U.S. or U.S. FDA, PMA?

Answer:

Dr. Borys whom I have met with the Head of the CDE, the Center for Drug Evaluation who has encouraged us not only to file quickly, assuming positive data but also to consider end points other than OS for example 3-year survival percentages.

And

So our strategy for filing and that's the direction I'm giving to our NDA team who's currently working on writing the NDA is China the United States and the European community in that order.

So it seems that in addition to the interim efficacy analysis per original protocol in July/August, they are at the same time doing alternative analysis for China in order to potentially get the drug faster to market over there.

IMO that gives us the second shot on goal during the summer. If we have successful interim efficacy analysis then that's enough for China too. But if hazard ratio isn't yet low enough at the first interim, there's still chance that alternative endpoint may give enough proof of efficacy for Chinese regulators.

[Antti]

Thank you. Let me know what you find.

I have known the company exist for almost seven years but have followed it only superficially for a long time. But now it caught my eye and it truly seems that they are finally, after all these years, ready to make a significant impact on HCC treatment landscape.

[Antti]

Yes, it does. But I assume it's going to get a lot busier once there are some definitive news like when the company announces the start of the interim analysis.

Anyway, I hope you will find the company interesting and decide to stay. Would love to see some of that quality discussion on our board to be transferred also here.

After all, IMO the size of the opportunity is almost similar with this company, even thought the indication and many other things are different.

However, there are some similarities too. For example their previous phase 3 (that too 5 years to complete) didn't succeed seemingly due to wrong treatment parameter (non-standardized heating time). That was a clear mistake but it made a bit more sense after listening the management explanation. If I recall, they were told that the heating time is usually left to doctors to decide. Since naturally the doctors should want to heat the tumor enough because that alone has a benefit. And the doctors know the patients best so they can take individual characteristics into account. So it was quite easy mistake to make in the previous trial IMO.

So now, after another 5 years of running the second "confirmatory" phase 3 trial, we are finally almost at the finish line again. And this time we have a luxury of knowing the previous phase 3 results, which should lower the overall risk considerably. And the reward has stayed basically the same since there hasn't been any competing breakthroughs in the HCC treatment in the meantime.

[Whoopddew]

Always looking for something I’ll check this out

[Whatsupp]

Antti, looks pretty dead over hear. I will look into the stock. thanks

[Antti]

The first phase 3 interim efficacy analysis is coming early in Q3 according to the latest CC. The hazard ratio that they need to hit in order to be successful already at the first interim is 0.61. Based on the subgroup in the previous phase 3 HEAT study (that is identical to the current OPTIMA study population) where the hazard ratio was 0.65, there's a good chance that this could happen. I estimate there's around 30%-35% chance of success at the first interim.

All quotes below are from Q4 and Q1 conference calls.

So, how are we doing? So far, the Data Monitoring Committee for the OPTIMA study completed their review of the fully enrolled population in December. From that meeting we have reported the following; in line with our previously communicated estimates we expect the 118th event to occur very early in quarter three 2019. We'll report the outcome as soon as possible following normal quality checks data formatting and the DMC's review. The second interim efficacy analysis if necessary will follow some six to eight months thereafter.

... from the 285 patient subgroup from the HEAT study, a group that is virtually identical to the OPTIMA study population.

Given that there are almost zero chance of futility at the first interim I think the risk/reward is very good at this point. Either we get positive results and the price soars almost instantly at least to $20-$30 (there are around 22,5 million shares fully diluted) or we get study continuation in which case we will have the second interim analysis within the next 6-8 months.

So if you've written those numbers down, you can plot that 0.65 somewhere between the first interim and the second interim. And the guidance we've been giving Matt is that, we don't expect, based on this analysis, that the first interim would be the one in which we claim to stop the study. It’s a chance, but that probability estimated by our statisticians is a -- it's less than 50%.

The market cap is around 40 million, let's summarize what we get with that money:
- About 25 million cash (including further planned NOL sales in 2019)
- Around 200 million invested in phase 3 studies alone in the last 10 years
- The drug that has clear blockbuster potential
- First interim efficacy analysis with clear chance of positive results ready in few months and the next one coming in 6-8 months with probable positive results (if the previous phase 3 data is repeated in the virtually identical study population)

IMHO all things considered, we have a great risk/reward here right now. Should the current phase 3 be successful, the drug could easily have yearly sales between 1-2 billion in which case the market cap should be around 3-8 billion. There are going to be some further dilution before those sales materialize so there may be around 35 million shares within couple of years. That would still mean share price between $100 - $250 in few years if we get positive phase 3 results.

[john1045]

Strong buy volume today and being accumulated nicely

[john1045]

From Yahoo message board:

Oppenheimer comments...
Celsion Corporation (CLSN) reported 4Q18 and provided a business update to investors last Friday. In focus, CLSN is approaching two interim analyses for ThermoDox from the fully-enrolled Phase 3 OPTIMA study expected in 3Q19 and 2020. We are encouraged by the DMC's December 18, 2018 assessment, highlighting a median PFS of 21.2 months as of the October 4th data cut-off. In addition, the earlier-stage OVATION II with GEN-1 continues to progress, enrolling patients for dose selection and safety. With 2018 year-end cash of $27.7 million, CLSN has ample runway to reach these meaningful potential value-creating catalysts, in our view. We remain bullish.

[john1045]

Nice volume today in first 2.5 hours and PPS trending up nicely!

[Matmar]

Sure, means they are confident in what stock price is going to bring us

[john1045]

You have to like all the Director's/Management buying stock!

[Matmar]

https://meetinglibrary.asco.org/record/170576/abstract

[0whammies]

And, what about today?

CLSN!

[whytestocks]

News: $CLSN Celsion Corporation to Present at NobleConXV - Noble Capital Markets' 15th Annual Investor Conference

LAWRENCEVILLE, N.J., Jan. 24, 2019 (GLOBE NEWSWIRE) -- Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, today announced that Jeffrey Church, Celsion’s Executive Vice President and Chief Financial Officer, will present at NobleConXV - Noble Capital Markets...

Read the whole news https://marketwirenews.com/news-releases/celsion-corporation-to-present-at-nobleconxv-noble-capital-markets-15th-annual-investor-conference-7548374.html

[john1045]

Looks very well like it could be as CLSN has a very good clinical pipeline and Thermadox due in 2019! GLTA!

[Jumpinjackas]

2019....to be its year?

[john1045]

Celsion Co. (NASDAQ:CLSN) CEO Michael H. Tardugno bought 7,500 shares of the business’s stock in a transaction on Monday, October 29th. The stock was bought at an average price of $2.06 per share, for a total transaction of $15,450.00. Following the purchase, the chief executive officer now directly owns 27,700 shares of the company’s stock, valued at $57,062. The transaction was disclosed in a document filed with the Securities & Exchange Commission, which is available at the SEC website.

A hedge fund recently raised its stake in Celsion stock. BlackRock Inc. lifted its holdings in shares of Celsion Co. (NASDAQ:CLSN) by 72.3% during the second quarter, according to its most recent disclosure with the SEC. The fund owned 114,844 shares of the biotechnology company’s stock after acquiring an additional 48,194 shares during the period. BlackRock Inc. owned approximately 0.65% of Celsion worth $339,000 at the end of the most recent quarter. Hedge funds and other institutional investors own 4.76% of the company’s stock.

https://www.fairfieldcurrent.com/2018/11/02/celsion-co-clsn-ceo-acquires-15450-00-in-stock.html

[john1045]

Robert Hooper, Director at Celsion purchased in open market 10k shares at $2.70. The Directors continue to do this is a good sign IMO. GLTA!

[Jumpinjackas]

Next year. This will be close to 20 or still here.

[carbonfiltered]

Good news- just icing while waiting for GEN-1 phase 1B study...

http://www.ox.ac.uk/news/2018-07-10-focussed-ultrasound-used-improve-effects-cancer-drugs