RE:RE:New PDC article mentionning TH1902 and TH1904Yes, as we've been saying, frankly any continuing good news around either ADC or PDC technology and efficacy for targeted cancer treatment is at least positive news. There's still only a few on the market. THTX can show a highly unique and helpful aspect to it's SORT1+ platform in a few different ways.
We have multiple shots to get that PR you talk about. It can be any of 1) showing a very high degree of safety/negligible SAEs to deal with despite having a chemo bomb attached; 2) it could be the unique attractiveness of throttleing doses and cycles in a more customized way because of that safety; 3) it could be the unique anti-metastic/VM interrupting aspect; or 4) all three.
The concept, if proven up, has a few ways to excite the oncologists and industry, eventually making its way to market excitement. If it works, the market will know and we'll be done with our anger and doubt (hopefully). I'm starting to think that there could have been a very useful reason for the investigators to convince THTX to drop down to what was seen as a very safe level (so far, we have been told there were no SAEs at 300), and still have a dose larger than normal plus the 4-7x internalization factor. An investigator is just as interested in bringing in a new form of effective treatment, a new useful target, as THTX management. It can provide them industry accolades for ever as the PI who ushered in and ran the trials for the drug. They could be jumping for joy that they have this unique combo of a higher dose, much higher internalization with no MDR, and negligible side effects for their patients. That's all they needed, so why push for more than 300? They want to get it to the actual human trial and move it along. I see that as a real possibility and something we should probe at the next call.
, so I saw a new paper written about a different topic (hypertension) and sortilin.
The most interesting fact I learned is this --in normal tissue only around 1/10th of the amount of sotrilin in a cell makes it to the surface. I guess that is what helps it become overexpressed in the advanced cancers --there's 9x the normal amount that can move to the surface for whatever reason it does. Here's the article and the quote.
jfm1330 wrote: We did not learn anything new about TH1902 out of this scientific article, but it shows that the scientific community is well aware of the existence of this program. A meaningful development about it will quickly make its way through the scientific and medical community. That's why I think that most of the promotion will be made through real good results. The better these results would be, the faster the information would spread around.
jfm1330 wrote: 4.2. PDCs in clinical trials
Although the structures of PDCs are similar to antibody-drug-conjugates (ADCs), these functional peptide conjugates offer several advantages over ADCs, including selectivity, deeper tumor penetration, rapid extravasation, and slower renal clearance. The PDC drug Lu-dotatate177 has been approved by the US Food and Drug Administration (FDA) for the treatment of gastrointestinal pancreatic neuroendocrine tumors [231]. However, there are more PDCs in the development stage, such as TH1902, a PDC with a docetaxel cargo for the treatment of triple-negative breast and ovarian cancer. TH1904, a PDC loaded with DOX, can be used to treat ovarian cancer. Both PDCs target the overexpression of sortilin 1 (SORT1) receptors in cancers, including triple-negative breast, ovarian, lung, colorectal, skin, and pancreatic [232]. Another PDC drug based on a composition called a bicycle peptide is also very popular. Bicycle peptides are usually 9–20 amino acids in length and have three cysteine residues in their sequence. These cysteine residues react with small molecule linkers to constrain the peptide into a rigid conformation. Bicycle toxin conjugate can be used as a transporter for drug molecules. The drug is attached to the bicycle peptides to ensure an unhindered conformation [233]. Several types of bicycle therapeutics have entered clinical trials for specific tumors [234] Table 5. summarizes the reported clinical research progress involving PDCs published on the US FDA website (https://www.fda.gov/).
https://www.sciencedirect.com/science/article/pii/S2666138122000160