Theratechnologies Inc T.TH

Trodelvy's most direct competitor in TNBC Ph 1 data released

[Wino115]

Here’s some Phase 1 results from the drug most see as the nearest direct competitor in TNBC to Trodelvy at this point (because TH1902 is not very well known!).  It’s from Daiichi Sankyo and Astra Zeneca and called DS-1062.

 

Data is from cutoff of Jul30 and for 44 TNBC patient cohort of the TROPION study.  Recall it’s a Topo1 inhibitor ADC.

 

 —-Objective Response Rate was 32% — in line with Trodelvy

 —- Disease Control Rate was 77% (disease control is total of complete, partial and stable disease).

 —- In TOPO-1 ADC Naive subset, ORR was 48%  —better than Trodelvy in apples-to-apples cohort

 —- Baseline had 11% with brain metastases, 68% 2 prior lines, 30% treated with TOPO-1 ADCs

 —- Disease Control “observed” beyond 7 months in patients with ongoing response

 —- No median Duration of Response reached at current date cutoff

 

Safety Summary:

 —-Grade 3 or higher TEAE’s in 23% (TEAE = Treatment Emergent Adverse Event)

 —- Serious treatment related TEAE’s in 5%

 —- Common ones of nausea, stomatitis in 50-60%

 

So seems the hurdle to beat is still around 35% ORR or maybe 50% ORR for those with high sortilin expression (so it’s proper cohort) and having a disease control rate that’s pretty high —so at least a bunch of stables and some partial and complete responses of 50% or hugher. 

[SPCEO1]

Given all the drugs in trials to fight cancer, the drug that TH-1902 might ultimately have to beat may also not have reported results yet. We are shooting at a  moving target. There are many drugs that using a different MOA to attack the same cancer and none yet that we know of that use the sortilin receptor. So, we have to hope TH's approach is a superior one to all the other approaches.

[Wino115]

I'll let the real scientist answer the hard questions.  But you are right that there's loads of studies out there and it's super dynamic.  Two interesting points are that there are fewer dealing with the advanced stages THTX is targeting initiallly,  The 3+ lines and total resistance, so literally no choices in the current arsenal. And the use of sortilin, which as we

[qwerty22]

10 Can a new Eu­ro­pean biotech make an ADC bet­ter than Pad­cev? In­vestors are putting up al­most $100M to find out by Max Gelman A new Eu­ro­pean biotech has put to­geth­er a near­ly $100 mil­lion Se­ries A, and its lead

[Wino115]

"Elands (CEO) highlighted a few reasons why he thinks ETx-22 could eventually prove successful down the line, saying preclinical data have shown the compound binds 10 times better to tumor nectin-4, its ADC linker is more stable than Padcev’s and it uses a toxin that is less toxic for the skin." Guess binding, linker stability and various toxic issues are the weak spots for Padcev

[jfm1330]

One thing Thera did not explain, and I made some research about that on the net to find some answers, is how sortilin expression compare to other receptors expression that are targets for other PDCs and ADCs. I did not find any data where you would be able to compare the levels of receptors expression.The only thing I found is a visual comparison from histological staining of sortilin expression

[Wino115]

Interesting stains. I toyed around with this too, getting nowhere.  But one thing that seemed to be true as I compared other targets is that it appears sortilin is in fairly low levels normally and has some concentration in the brain and a few other organs.  It doesn't appear to be in concentration in many places in the body.  Secondly, it seems the differential becomes

[qwerty22]

I think the individual studies is the scientific literature are fairly good guides but eventually this needs to be proved empirically. I had a go at comparing trop1 to SORT1, got a little way through the process with a general conclusion that they were comparable but quickly gave up because the more I looked the less I liked my ability to draw meaningful conclusions. IHC just doesn't lend

[jfm1330]

I found the relative expression of sortilin in different tissues of the human body. The level of expression is given in "RKPM", which stands for "reads per kilobase million". Honestly, I don't understand exactly the meaning of RKPM, but it relates to RNA sequencing, and RNA is the direct result of gene expression and peptide and proteins are made by decoding RNA.  At

[qwerty22]

What seems to stand out in cancers is that the SORT1 is directed to the outer membrane. In many tissues it seems SORT1 sits mostly on internal membranes and does it's "sorting" job of shifting components to various compartments of the cell. I think in brain neutrons it's also externally expressed but from what little I remember about its role in liver it's as an internal

[scarlet1967]

I believe the basket trial is addressing same combination for different tumors so if the PDC is tried on multiple tumour indications then the agency backed by results can approve the drug for multiple tumours. It seems like if they can show PoC on 4 or 5 tumours then their PDC could be approved for all those tumours based on one trial(basket trial).

[qwerty22]

I think the unique MOA is key, that's what gives them the potential niche. How SORT1 holds up as a target and the profile of the drug decides whether they get the approval and what place the SORT1 tech takes with respect to other drugs in the clinic. We know cancer finds ways around probably all drugs so more ways to tackle cancer are essential. I think Wino is right in pointing to the ORR of

[qwerty22]

Here's a different ADC that got approved a few months ago for recurrent cervical cancer. This had an ORR of 24%, average  DOR of 8.3 months. Some patients got >36 months when expectation were max 12 months for anybody with this diagnosis. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tisotumab-vedotin-tftv-recurrent-or-metastatic

[Wino115]

This is one of our better comp models to think about how Theratech could develop strategically.  SeaGen has gone from 1 ADC approved to 4 within 2 years.  That is clearly how THTX thinks about their own SORT1+ platform.  They will have the resources to not just further the existing peptide with various combo's and conjugates to attach, but also develop other peptides for other