Theratechnologies Inc T.TH

Fitting

[SABBOBCAT]

It is king of fitting... We'd July 15, 2021 is a day that will never come... Just like the start of the NASH Phase III... I am joking of course, but come on, release the protocol already

[SABBOBCAT]

kind of fitting* and Wed*. I obviously use the same proof reader as TH lol.

[qwerty22]

This is a technical question more than anything. Don't you need the cash in the bank before you start a clinical trial? I can't think of any circumstances where that hasn't happened. I can't think a CRO would start a trial without that sort of guarantee. Won't they need to do a cash raise before the trial?it seems like another reason to wait for shrinking tumour. A flurry of

[SPCEO1]

For a trial that is going to last 3.5 years at a minimum, you do not need all the money for the entire trial up front. For example, GALT estimated their phase II/III trial would cost about $100 million and raised less than $50 million before launching it. That being said, we know another cappital raise is on the way despite the fact the company indicated the last one gave them a two year runway (I

[scarlet1967]

”As at August 31, 2020, cash, bonds and money market funds amounted to $26,847,000.” ”We ended the first quarter of fiscal 2021 with $56,716,000 in cash, bonds and money market funds.” The offering grossed  about $46,000,000 after fees the net proceeds were about  $43,424.000 adding  that to $26,847,000=70,27,.000( deducting the cash last quarter), 70,27,000-$56,716,000= $13,555

[scarlet1967]

I need to correct myself here as I deducted $3M from cash burn in fact a good portion of that not earned revenue is accounted for Trogarzo sales which is shared with Taimed also they have added few new recruits and a board member so they have more folks on their payroll. It was also based on the assumption that they paid good amount of money to constants but if they do increase revenues it can

[Wino115]

I'm sure their budget balances, but you are right that expenses have to be up. I would brace for seeing them up quite a bit myself.  The burn rate has to be up unless they culled some sales staff and middle ranks and really tightened their belt elsewhere.  They aren't hiring cheap people.   The budget probably has some "hopes" built in too that sales grow a bit. I

[qwerty22]

So sorry I should work this out myself but let's say they raise cash in late 2022 how much cash can they earmark for NASH before then, putting aside some for cancer etc? Presumably they want to enrol the 1000 patients ASAP.

[Wino115]

The good news is the TH1902 phase 1 is relativey inexpensive as trials go, and they've said that.  Phase 2 will also not be that costly given the smallish likely number of patients done in P2 for cancers. But of course if they get to Phase 2, there should be no worries on cash flow and financing options.   If they don't, that money can all go to NASH.   The ramp up for the

[palinc2000]

Exercise of the warrants will add US 26.5 million .The added dilution resulting from the exercise of the warrants will on the other hand make it more difficult for the Convert to be in exercise territory

[scarlet1967]

I will add to what has been said my take re the possible scenarios which can play out between now and end of 2022. It is somehow hard to calculate but let me have a go at it, looking at their income statement for 2020 there are operating expenses with sub categories like variable direct costs (trackable) such as cost of goods, R&D expenses, indirect variable costs (not trackable to a specific

[jfm1330]

For a very effective cancer drug, the path to approval can be pretty quick. A phase I followed by a phase II on 100-200 patients. Look at Blenrep, an ADC approved in August 2020 in relapsed refractory multiple myelomas. They did a phase I on 73 patients with differents doses. Than, a phase II testing two doses on 218 patients. The primary endpoint goal was 15% overall reponse rate (ORR). They were

[SPCEO1]

I think we should drill down as best we canon the timelines for TH-1902's pahse I and possible phase II trial. The 3/21 endpoint for the phase I on Clinicaltrials.gov needs to be updated for the info the company gave at the webinar. The last slide if the presentation indicated we will get a safety and preliminary efficacy readout on the phase 1a in Q4, that the dose escalation and MTD

[jfm1330]

Marsolais said during the presentation that if there is efficacy in part I of the trial, they will wait to see the full effect through multiple cycles of treatment, but at the same time he said that since they have fast track status, they would quickly meet with the FDA to decide what to do next. To me this is a very volatile situation at this point. I say volatile in the sense that nothing is

[SPCEO1]

i suppose if we see any preliminary efficacy in phase 1a, it will have the best chance of occurring if the trial goes a full 28 weeks without having to stop because of toxiicity issues arising. Or, even when such issues arise, the trial continues using the previous dose. If so, the question then becomes one of whether those doses were given to patients with sortilin expressing tumors and how many

[qwerty22]

Note at bottom of p42 "1 If ≥2 patients in a dose cohort experience an emergent DLT by Day 21 of the first treatment cycle, dose escalation will stop, and the prior dose level will be declared as the MTD. MTD is defined as highest dose level at which ≤1 of 6 patients in a cohort develop an emergent dose-limiting toxicity;" Identifying DLTs has to be an ongoing, real-time process

[jfm1330]

Remember that if the MTD ends up being very high, like three times MTD of free docetaxel, the phase Ia will be longer. Again, at this stage the timelines are not the most important thing. The only thing you really hope for is a long phase Ia, because it will mean a high MTD, so low relative toxicity, and that would be a very good sign for potential efficacy.

[SPCEO1]

Since I have no experience in this area, could you explain to me why phase 1a might go longer than 28 weeks if the MTD is ends up being roughly 3x that of free docetaxel? And can you know how much longer it might go? I can guess but I could easily guess wrong. Thanks in advance for the help on this.

[qwerty22]

Look on p42. The part 1 cohort is between 15-25. You enrol 3 patients at a dose. If there are 2 DLT you've reached your MTD and escalation stops. If you have 1 DLT you enrol 3 more patients at the same dose (bringing the total no. of patients receiving their first cycle dose at that dose to six) if another DLT emerges you've reach MTD. If a DLT  doesn't occur then you move up a

[SPCEO1]

So, how do you read what the company has told us thus far? Given a straight 28 weeks with no DLT's would put us in mid-September, do you think the slide that says we will get safety and preliminary efficacy results in Q4 suggests there has been some DLT's thus far, thereby lengthening the trial? If so, whay would they include the 28 weeks for phase 1a in the slide and not update that info

[qwerty22]

I find it as confusing as you, don't be sorry. I think it's some sort of mix of contingency, time to talk to the fda, allowing Paul to say he's beat expectations again. Maybe this is a favoured approach of LSA to guide later and deliver earlier. Christain said at the time of the KOL event that each step on the dose escalation ladder was taking about 4 weeks. It didn't sound like

[scarlet1967]

    What you say makes sense also the first two levels levels can be more than 2 as they need to see DLT before moving to the first 3 patients so it can take longer than 28 weeks. “Three patients are usually treated at a dose level and observed for acute toxicity for one course of treatment before any more patients are entered. If none of the three patients experience DLT, then the

[scarlet1967]

The dose escalation can take longer as they will be dosing a single patient during the first two cycles until DLT is shown if not they keep dosing therefore they  add more levels of dosing to the program so essentially they could end up with more cycles but I believe the cut off for the MTD will be at 560mg/m2 therefore the MTD can't be three times more than Docetaxel as per company their

[scarlet1967]

The part 1 phase 1 has apparently 20 patients and part 2 40 additional patients versus most likely 200 or more patients in phase 2 and more patients in phase 3. Although the primary endpoint for phase 1 is safety that's the phase will least amount of patients therefore pumping patients with extremely high dosage can back fire as the risks for grade 3 or above toxicity will increase during

[jfm1330]

I listened again to the presentation part on toxicity and dose escalation. Marsolais said that in their toxicity studies for IND on rats, the MTD was three times docetaxel. The only thing we don't know is if these rats had xenograft tumors or were healthy rats. That's one thing, but in the explaination in the dose escalation part, he says that they expect to reach MTD of TH1902 in humans

[jfm1330]

Obviously I meant several phase IIa, so testing on many types of cancer at the same time. The same idea as their basket trial, but really more like a phase IIa, so the first part of a larger trial that could lead to approval. Obviously to get that from the FDA they would need excellent efficacy early on. This is just a guess on my part, but if early efficacy would relly be excellent with clear

[jfm1330]

Marsolais said that reaching MTD at the begining of the fall is possible. So let's say it is in mid-October, the two more cycles to better assess efficacy. You end up at the beginning of December. Meeting with FDA and preparing for phas Ib or phase IIa, like I wish for. But starting the next part of the trial in January 2022 is not a problem, because then they will start with the right dose

[qwerty22]

Summer will be quiet. From late Aug onwards things might start to happen through to the end of the year. That seems like the take home message. It may be a fact that it takes longer for good news to emerge than bad news in this scenario. So the longer we wait the better.

[Wino115]

or both approaches

[jfm1330]

Obviously, both are possible, that's the beauty of a drug with a large therapeutic window. In the future, with easy sortilin receptor imaging (they will get there one day!!) that will make it easy to assess sortilin overexpression on tumors, they could modulate the dose in relation to expression. That would be flexible personalized medecine. About sortilin, I fell on an interesting link about

[SPCEO1]

JFM1330 - thank you - that was an awesome response and I appreciate the effort you put into it. So, if things go as well as we all hope they will, it sounds like we should expect the phase 1a to end sometime in November. That fits with the timelines in the last slide of the presentation and makes sense to me. If TH reports data earlier than that, then we will know the trial did not quite go as far

[qwerty22]

The other thing we don't know is if rat Sortilin is homologous to human Sortilin and if the peptide binds to both with similar affinities.

[qwerty22]

They don't have to reach MTD. If they get to the top dose without DLTs (and with efficacy) they could just stop there and declare they haven't reach MTD. Like this drug. https://link.springer.com/article/10.1007/s00280-013-2277-8 or this combo trial. https://www.sciencedirect.com/science/article/pii/S000649711954900X

[Wino115]

All interesting and what this analysis all points out is that, like the PDC, this 1a trial is fairly unique.  What is unique is that it if we understand the workings of this PDC reasonably (which I think we do from the component and theoretical side), then this 1a timeline really will tell us some extremely important things about the ultimate efficacy, and that is not at all usually the case.

[palinc2000]

At what point do they determine that MTD has been reached,,,How is toxicity defined? Is there a time factor involved,,,?Can toxicity be reversed after a a few days .....?  

[Wino115]

I believe that was all covered by many in yesterday's posts. DLTs, SAEs, their max dose limit, etc...  

[SPCEO1]

One of the science experts here should answer this but I will take a stab anyway: 1.) The MTD will be determined by stepping back one dosage level from the dosage that leads to two or more patients showing signs of toxicity. So, you can have one patient outof an eventual 6 who has a bad reaction to a dose and still make that your MTD. Clearly, TH is looking to be able to pump as much Docetaxel

[qwerty22]

https://case.edu/cancer/sites/case.edu.cancer/files/2018-06/Dose-Limiting-Toxicity.pdf

[qwerty22]

All sorts of grade 3 and beyond toxicities. Just bare in mind this is a very technical, defined process designed just to find a working dose. It's not really defining the full safety profile of the drug, that comes later, although I guess it's a pointer to that. I read this 3+3 MTD process typically leads to a situation where the drug gives grade 3+ events in 40-70% of patients in the

[scarlet1967]

The DLT is at grade 3 or above, the toxicity is graded from grade 1 to 5. Apart from 5( lethal consequences) all other grades are reversible hence the higher grades the more need of intervention, treatment and longer recovery. At the end of each cycle patients  are reviewed for safety data so one can presume if there are any toxicity it will be detected  there and then. The

[palinc2000]

I have suffered big financial losses when a Phase 3 trial  which was scheduled to be unblinded after a certain number of eventd( deaths)went on and on  for many more months  because the patients on placebo lived a lot longer than anticipated and about the same as those on the drug,Total failure!!! So I think we need to be careful as some pointed out to rely too much on the time

[scarlet1967]

I think the longer we don't hear from the company it means the trial still processing thus no serious issues specifically in the first few cycles until they get the MTD, the schedule is 28 weeks if the process is flawless theoretically it wil account for 9 cycles but again it can be more than 9 cycles due to the fact they keep dosing single patient /patients until DLT is observed so the first

[qwerty22]

I don't quite understand what you mean. There is no placebo in this trial. At a very simplistic level we want efficacy to come as early as possible and toxicities to come as late. But the timing of when the company goes public with these things may not follow that exactly. From the discussion we had yesterday it seems to me they've given themselves a fairly wide timeframe in which to

[palinc2000]

Qwerty I know there is no placebo in this trial....  Just pointing out that time is not necessarily a relevant factor .... Sorry for not being clear  

[SPCEO1]

Does the way the last slide in the presentation reads possibly indicate that they have already decided to add some higher doses which will take the determination of the MTD out to the end of the year? I doubt it but I am also confused that they would not be able to report the MTD sooner. They are planning on reporting interim data sooner, as indicated on that slide, but are we to assume then that

[qwerty22]

Lol, I think this is just us sweating the details too much. Normally I rely on you to go above that and present the bigger picture. Seems like you've descended to our level! Happy holidays

[scarlet1967]

"As for MTD at any dose  level if grade 3 toxicity is shown the MTD will be the previous lower dose" Again I have to correct myself, if grade 3 toxicity is observed during single patient dosing then that would be the DLT for that dose NOT MTD then they move to 3+3 with a lower dose. I think it's a lot of discussion round dose escalation and science lately which is great

[Bucknelly21]

exactly what I said would happen Lsa wouldn't do it for them only show them how...

[realitycheck4u]

This post has been removed in accordance with Community Policy

[Wino115]

yes, the low volume is still an overall negative from an investor viewpoint.  On the other hand, seeing a rising price on still low volume is indicative of someone building a position, so perhaps we have seen the last of the OO retail puke.  This earnings report may be the test if the analysts downgrade earnings, which they should.  They probably won't change targets, but reset

[scarlet1967]

The offering was definitely a set back but really the rising price and building positions argument doesn't sound right to me. Since they purchased Katana and announced the move to HIV NASH the valuation is about the same as it was then, despite the fact the oncology has progressed from preclinical to clinical and they are perusing much bigger general NASH. Also with ongoing short volume

[qwerty22]

In my mind MTD came before interim efficacy/safety. Mostly because data that informs MTD only comes from each patients first drug cycle. Data is collected up to and including the highest dose so it can't readout too early, but it's limited to each patients first cycle so it can't readout late. I hadn't imagined the analysis was too complex so it seems to fit into a fairly narrow