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   Biotech / MedicalImmunomedics (IMMU) - moderated


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To: patlawche11 who wrote (45906)4/27/2018 5:58:51 PM
From: drtom1234
6 Recommendations   of 53125
 
It occurred to me this morning that this may actually be a very significant event. To my mind, it suggests that they have accrued enough patients in both hormone positive breast cancer, as well as urothelial cancer to satisfy the FDA requirements(which presumably have been communicated to the company during FDA meetings) for accelerated approval in these two indications. I suppose other alternatives are that they are planning separate P2 studies in both urothelial and breast to complete accrual of necessary patients, OR, they aren't planning on AA in one or both indications. The first of those options seems unnecessarily onerous and expensive when they could have easily accrued the patients under the auspices of the already existing basket trial. The second option seems unlikely especially in urothelial. In terms of breast, we'll know quite a bit more after June 3rd.

In terms of timing, if we assume the last urothelial patient was just dosed, and PFS for urothelial is a median of 7 months, by early next year(significantly sooner than I had initially thought) they could be ready to apply for AA. If I play devil's advocate, the Cowan presentation on the company website suggests that at least in March, the company thought they would need more patients admitted; maybe they received input from the FDA that they had enough? I don't know, but we should have more clarity from management in 37 days.

In terms of hormone receptor positive breast we have no idea of the efficacy of SG yet, but presumably PFS would be longer than for TNBC, which is about 5 1/2 months. We also know that the combo of palbociclib-plus-fulvestrant given in metastatic hormone receptor positive breast cancer patients has a PFS of 9.2 months in patients who had received one prior chemo(PALOMA3 trial). Presumably SG will be positioned as a 3rd line agent, so I would expect the requirement for PFS would be less than that, but would also expect it to be longer than the 5 1/2 months in TNBC.

Needless to say, if we were to get AA in TNBC, urothelial, AND hormone rec pos breast, even 3rd line for all indications, valuation of the company will be vastly increased, and I would expect to see huge acquisition offers from big pharma.

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To: drtom1234 who wrote (45929)4/27/2018 9:09:22 PM
From: weatherproof
7 Recommendations   of 53125
 
My thought is that they set out accruing a minimal amount of patients for the first stage in a 2-stage phase II. It is my sense that the response rate in both urothelial and hormone positive BC were high enough to reject the null hypothesis (drug inactive due to lower than a predetermined response rate.) I'm also doubtful that the trial was stopped for efficacy. I think we're just seeing the trial suspended as they take the numbers from the basket trial representing stage one, and now determining the sample size, and such, for the second stage. The bad news would have been that they're not proceeding with the second stage due to inactivity of the drug or some issue with toxicity. I don't believe we're seeing any signs of that.

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From: winners184/27/2018 11:12:37 PM
   of 53125
 
Is he still on immu payroll?

http://www.pegsummit.com/

4:50 Trop-2 as a Broad Solid Cancer Target for Antibody-Drug Conjugates

David Goldenberg, ScD, MD, Founder and Former CSO, Immunomedics, Inc.

Trop-2 is a transmembrane glycoprotein that transduce cytoplasmic calcium signal, activates MAPK/ERK pathway, and affects cell-cell adhesion. Using a proprietary linker technology to site-specifically conjugate an average of 7.6 molecules of SN-38 (the active metabolite of irinotecan, which inhibits nuclear topoisomerase I) per humanized IgG, my group demonstrated effective and selective tumor inhibition in vitro and in xenograft solid tumor models, as well as in phase 2 studies of ~500 patients with advanced, heavily-pretreated diverse solid cancers (e.g., breast, NSCLC, SCLC, urothelial).

Limitations of First-Generation ADCs in Solid Cancers

David Goldenberg, ScD, MD, Founder and Former CSO, Immunomedics, Inc.

Prospects for next-generation ADCs in solid cancersRole of antigen target, drug-antibody ratio, nature of drug, conjugation chemistry, drug resistance.

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To: weatherproof who wrote (45930)4/27/2018 11:38:36 PM
From: drtom1234
   of 53125
 
I agree that RR based on available information is likely to be quite good. I don't think the trial was stopped for efficacy either, I just wonder if they have accrued enough patients in those indications to satisfy FDA requirements for AA. Starting studies up is expensive, and I'm not sure why they would need or want to spend that money on two new P2 studies(urothelial and ER+ breast), when they could satisfactorily accrue those patients under the umbrella of the pre-existing basket trial, just as they did with the TNBC indication.

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To: winners18 who wrote (45931)4/28/2018 12:12:16 AM
From: dorightbythem
   of 53125
 
First, oy. Second, 500 patients larger than expected.

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From: dorightbythem4/28/2018 8:08:12 AM
   of 53125
 
Third, let's hope he doesn't pull another fiasco, inadvertently.

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To: drtom1234 who wrote (45932)4/28/2018 8:18:06 AM
From: weatherproof
3 Recommendations   of 53125
 
I was wondering if "active, not recruiting" simply means they're temporarily halting the trial as they work the numbers in the first stage of the analysis and plot out the next stage. That wouldn't be inconsistent with how they handled TNBC. In fact, I recall that Chau believed that after the pause in TNBC accrual, and then subsequent resuming of the trial with the recommended additional patients for the second stage, that resumption (and the inferred FDA nod) would be a positive share price event. It turned out not to be but I cannot recall if that was due to a market yawn, a terrible financing, and/or the FIASCO happening concurrent with said resumption.

In retrospect, I get the basket approach and why moving forward with the second stage of the 2-stage analysis for TNBC should have been a stock moving event. I'd be surprised to learn that IMMU didn't frame out the resumption of stage 2 for urothelial, for instance, in that context. I'm thinking it may be worthy of a press release if and when that trial resumes, signifying that stage 2 is moving forward.

Two stage approaches are common in phase II studies. You can look at a minimal patient population so as not to potentially subject a larger group to ineffective treatments, assuming the null hypothesis (drug ineffective) to be true. After all, in most cases a drug does fail in phase II. It also is a way to mitigate the financial strain of funding a larger study. I don't know how IMMU structured the 2-stage analysis, but one can contemplate that:

1. There is some threshold in terms of response rate below which the study won't move on to the second stage.
2. There is some RR above which the trial may be halted due to efficacy, which will result in going straight to the AA application.
3. I think what we're seeing here is something in between. IMMU-132 in urothelial, for instance, is seemingly active and efficacious. Given the results in the first stage of the analysis, and given a desired significance level, say 5%, and study power, how many patients do they need to accrue in the second stage for the alternative hypothesis to be borne out.. They can increase the power by raising the significance level from 5% to something larger, but by doing so, they'll increase Type 1 errors (reject null hypothesis when it was true, meaning that they move forward when the drug is really inactive.)

I don't mean to get in the weeds, but it has always been my impression that to understand how things have been moving forward over the past couple years, one would need to understand the premeditated 2-stage approach to these phase II trials. And, by the way, I do not for a second pretend to be any kind of expert in this statistical arena.

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To: weatherproof who wrote (45935)4/28/2018 10:18:33 AM
From: Smoke Reader
1 Recommendation   of 53125
 
For what is worth, I am quoting from the Glossary of Terms at ClinicalTrials.gov... clinicaltrials.gov
***START QUOTE***
Recruitment status: clinical study
Not yet recruiting: The study has not started recruiting participants.
Recruiting: The study is currently recruiting participants.
Enrolling by invitation: The study is selecting its participants from a population, or group of people, decided on by the researchers in advance. These studies are not open to everyone who meets the eligibility criteria but only to people in that particular population, who are specifically invited to participate.
Active, not recruiting: The study is ongoing, and participants are receiving an intervention or being examined, but potential participants are not currently being recruited or enrolled.
Suspended: The study has stopped early but may start again.
Terminated: The study has stopped early and will not start again. Participants are no longer being examined or treated.
Completed: The study has ended normally, and participants are no longer being examined or treated (that is, the last participant's last visit has occurred).
Withdrawn: The study stopped early, before enrolling its first participant.
Unknown: A study on ClinicalTrials.gov whose last known status was recruiting; not yet recruiting; or active, not recruiting but that has passed its completion date, and the status has not been last verified within the past 2 years
***END QUOTE***

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To: Smoke Reader who wrote (45936)4/28/2018 11:12:44 AM
From: weatherproof
4 Recommendations   of 53125
 
Thanks, Smokey. I should have looked that up before I started my last post, but I suppose it doesn't fight with my working theory.

Friends have asked me if they should buy the stock now. I cannot answer that for anyone, as I do not know their financial situation, their current investment portfolio in terms of how diverse it is, or one's tolerance for risk. Nor am I qualified to answer such questions. What I will say is that the manner in which IMMU and others (e.g. Royal Pharma) are investing in ramping up for commercialization of IMMU-132 before approval, suggests that there is an extreme level of confidence pointing toward accelerated approval being imminent. If you've ever cursed yourself for not buying, or buying in early and then selling prematurely, Apple or Google in the beginning stages of those issues, I suppose this is what those foregone opportunities looked like way back when. Does that mean we're definitely going to the moon, that there is no risk? Of course not! I'm simply suggesting that this is an exciting time in IMMU's life cycle to be in it. We're at the intersection of fortune and folly.

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To: weatherproof who wrote (45937)4/28/2018 11:31:03 AM
From: Renmanco
3 Recommendations   of 53125
 
One of the most challenging aspects of investing in these early stage companies is dealing with the volatility....and the accompanying psychology.
It is not uncommon for such stocks to have swings of more than 30, 40, 50%....or more on an irregular but recurring basis and the temptation/fear is that "someone knows something that I do not....and I had best either nail down my profit and/or sell before the loss becomes greater."
I great anchor at these times is to reexamine the company's basic fundamental story, including a review of insider ownership and see what those really in the know are doing with their shares save for taking small increments off the table periodically to diversify what are typically oversized positions.
I recall doing a study of Medtronic about 20 years ago tracing its IPO through the date of my study. The number of 50%++ swings was very frightful to say the least but the overall compound return over 30 years was astounding. Lesson learned.
Just look at the volatility of IMMU since its IPO. Huge price swings...and no real net progress. Finally, we had a series of terrific catalysts and I suspect they are only the beginning of what I'll call a redemption for long-term holders. The fact that G and S have been exiting is another perverse catalyst that I really like seeing.

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