scarlet1967 wrote: I posted the below not long ago confirming what you said. In my opinion at times the investors were too optimistic about oncology and since the pause too pessimistic for instance Q was saying TH1902 will never be injected in another patient which at the time was a premature guess happened to be incorrect! I can understand lack of details of their findings/analysis have been being bugging him and many others including myself but not revealing it doesn't mean they don't know what they're doing unless all those scientists working for the company internally and externally are absolutely clueless.
Under the terms of the agreement, Genentech and Bicycle will collaborate on the discovery and pre-clinical development of novel Bicycle-based immunotherapies against multiple targets. Bicycle will receive a $30 million upfront payment. The upfront payment and potential discovery, development, regulatory and commercial-based milestone payments could total up to $1.7 billion. Bicycle will also be eligible to receive tiered royalties on Bicycle-based medicines commercialized by Genentech."
Bicycle Therapeutics Announces Exclusive Strategic Collaboration with Genentech to Develop and Commercialize Bicycle®-based Immuno-oncology Therapies | Business Wire
“We look forward to working closely with Novartis to pioneer the discovery and development of potential new cutting-edge radiopharmaceutical cancer treatments based on Bicycles. We believe the properties of Bicycles make them well suited for the development of precision guided radiopharmaceuticals and represents the next leg in the application of our proprietary discovery platform in oncology. Novartis will fund all pre-clinical and clinical development and commercialization activities. Bicycle will receive a $50 million upfront payment and is eligible for development and commercial-based milestone payments totaling up to $1.7 billion. Bicycle will also be eligible to receive tiered royalties on Bicycle-based medicines commercialized by Novartis."
Bicycle Therapeutics Announces a Strategic Collaboration with Novartis to Discover, Develop and Commercialize Bicycle® Radio-Conjugates | Business Wire
Different MOAs/approaches compared to Sort1 technology but early stage collaborations with decent upfront payments,etc.
One could argue possibly Bicycle's progress so far for their PDC projects has to do with the demand/interest from other companies nevertheless these partnerships are based on preclinical research yet to be investigated by clinical trials!
"Under the terms of the agreement, Genentech and Bicycle will collaborate on the discovery and pre-clinical development of novel Bicycle-based immunotherapies against multiple targets. Bicycle will receive a $30 million upfront payment. The upfront payment and potential discovery, development, regulatory and commercial-based milestone payments could total up to $1.7 billion. Bicycle will also be eligible to receive tiered royalties on Bicycle-based medicines commercialized by Genentech."
Bicycle Therapeutics Announces Exclusive Strategic Collaboration with Genentech to Develop and Commercialize Bicycle®-based Immuno-oncology Therapies | Business Wire
“We look forward to working closely with Novartis to pioneer the discovery and development of potential new cutting-edge radiopharmaceutical cancer treatments based on Bicycles. We believe the properties of Bicycles make them well suited for the development of precision guided radiopharmaceuticals and represents the next leg in the application of our proprietary discovery platform in oncology. Novartis will fund all pre-clinical and clinical development and commercialization activities. Bicycle will receive a $50 million upfront payment and is eligible for development and commercial-based milestone payments totaling up to $1.7 billion. Bicycle will also be eligible to receive tiered royalties on Bicycle-based medicines commercialized by Novartis."
Bicycle Therapeutics Announces a Strategic Collaboration with Novartis to Discover, Develop and Commercialize Bicycle® Radio-Conjugates | Business Wire
Different MOAs/approaches compared to Sort1 technology but early stage collaborations with decent upfront payments,etc.
One could argue possibly Bicycle's progress so far for their PDC projects has to do with the demand/interest from other companies nevertheless these partnerships are based on preclinical research yet to be investigated by clinical trials!
palinc2000 wrote: It used to be that big pharmas preferred to get involved at a much later stage of drug development before partnering even if it meant paying more... I think this is no more the case and there are more and more deals for early stage trials.
I wrote a few weeks back that THTX had only 2 options for the oncology platform :either put an end to the development or continue with a deep pocket partner.... The company seems to be saying that once they get FDA approval they will restart the trial "slowly" while searching for a partner as soon as there are signs of positive results...
Unless they get an upfront payment from a partner in Nash the number of months they can afford to show positive results to attract a partner is very limited...
No fun to operate in a straight jacket but this is where we are now ......
qwerty22 wrote: "On the other hand, I can see the ability to attract a partner purely on the CPI/TH1902 combo changing the entire dynamic in cold tumors if the data holds up strongly."
For me there's a few more boxes to be ticked before that happens. Maybe they can get Merck to provide some free pembro for a trial but that would not amount to much, Merck does this with immeasurable numbers of drug developers. Having said that the market sometimes buys into these deals. THTX has so under-delivered then maybe any news would be leaped upon.
Generally I think you're over-stating the depth of any potential deal on the combo trial front. The early deals I've seen tend to not involve money exchange. Both companies hold onto the rights of their own drugs and typically the junior partner is mostly covering costs. It's just a fact that THTX needs a good CPI more than most of those CPIs need SORT1 tech.
I'm just generally not that excited about this atm. It's back to preclinical and a long, more complex and more expensive path if it gets off the ground.
It seems from what little we've seen that they don't have an idea on the mechanism behind this. Maybe this synergy is as surprising as hitting the brick wall in Ph1 was, IDK. An MOA for this would help. I've got one but I'm pulling out of a not so clever part of my body. I want TH1902 to be depleting Sortilin on the surface of tumour cells and this to be shifting the tumour towards being "hot" by suppressing anti-inflammatory processes. I'm making that up just to be clear.
So IF they had something more positive from their mono therapy trial and/or IF they had a MOA for why th1902 might be making tumours more immunologically "hot" then maybe those would be the boxes to get a tick to make a combo deal a more exciting prospect.
The best option atm seems to be their short term aims which seem to be much greater targeting of the right patients for the Ph1 mono therapy trial.
Wino115 wrote: You're right. I recall them talking about checkoint inhibitors quite a while ago (I think it's even mentioned in their pipeline oncology presentation from 2 years ago), and now it seems they've focused on the anti PD-L1 angle within the broader immunotherapy market. I didn't know enough about CPIs to connect PD-L1 to it. This test was only on melanoma, but the CPIs are used on all sorts of solid tumors now --lung, breast, etc. I guess they picked melanoma for the reasons they stated, it's the standard of care for them and they are the most immunogenic. So if you can get that CPI into the cold tumor with your combo, even just a little, you're expanding a standard treatment to another whole class of tumor-types.
I think they agree with you, as we all should, that it would be imperative to still show response, safety and efficacy in at least one kind of tumor in humans as a monotherapy too, maybe even just safety and stability readings (although that's on the weak side). It "squares the circle" as you say. That would add a whole lot more and they mentioned that in the call.
On the other hand, I can see the ability to attract a partner purely on the CPI/TH1902 combo changing the entire dynamic in cold tumors if the data holds up strongly. We'll see what it is next week. Reason being we have plenty of examples specifically in the PDC area of companies partnering off pre-clinical data in very specific uses/tumors/combos where they can get in early and cheap and drive a deal to their liking. Bicycle did that with a few indications. Let's face it, THTX will take any reasonable deal and try to "circumscribe" it to keep it very specific as it would finally lend credibility to the Sort1 platform. Let alone, they need the money! I'm fine with that since it wouldn't be giving away the whole platform, hopefully just the immunotherapy combo side. Anyway, getting way ahead of it without seeing if these numbers are statistically significant and very strong. I assume since they said they've never reached out domestically to any partner (only China), that this would be one more angle to put on the partnership discussion table if it gets to that, which I hope it does.
One thing about opening up partnering opportunities in North Amer, there's a whole lot more companies vying in the marketplace, relying on these kind of partnerships for future growth (the "shrink the RD dept" factor), have money specifically for deals like this, and would need to beat their competitors to the table. Two big "ifs", but if the data is solid, if they can negotiate smartly, they may be able to move it ahead quicker than expected regardless of waiting around for a restarted monotherapy result trial. It still may be a novel and exciting enough finding to explore clinically. The dose level was half the normal dose of docetaxel, so in a much "safer" level according the the original dosage trial data where there were no SAEs at the 150-200 levels. So you could trial it just based on that safety signal, regardless of current efficacy issues. They'd be nice to see, but maybe not necessary. THTX should tell us more on that though as I'm purely guessing.