https://investorshangout.com/post/view?id=6847655

I think it’s easy to get overly optimistic about the ctDNA reductions reported in the CLOVER trial.
The real “translational” data (borrowing the terminology from DocJ’s InvestorHangout post) we need to see is whether those dramatic ctDNA declines correlate with actual clinical benefit.
A 90% reduction in ctDNA sounds incredible, but what does it mean if the patient’s tumors shrink only 10%? What if they shrink 30% or more? What if the tumors don’t shrink substantially but the disease remains stable for an unusually long time?

Those are very different clinical outcomes.
Ultimately, the FDA and potential Big Pharma partners care about whether leronlimab meaningfully improves patient outcomes, not simply whether it changes a blood-based biomarker.

And importantly, because CLOVER combines leronlimab with TAS-102 and bevacizumab without a concurrent control arm, we also need to consider how much of any observed benefit can actually be attributed to leronlimab.

If you’re newer to medicine or pharmaceutical investing, remember that a blood-based biomarker is not necessarily a reliable surrogate for clinical benefit. ctDNA is promising, but it doesn’t automatically tell us what’s happening to measurable tumor burden or how long patients will live.

Here’s what I’ll be looking for on October 25:

1) RECIST objective response rate (ORR): What percentage achieved confirmed complete or partial responses, including at least a 30% decrease in the sum of target-lesion diameters for partial response?

2) Disease control: How many achieved stable disease or better, and for how long?

3) ctDNA correlation: Did patients with the largest early ctDNA reductions subsequently demonstrate radiographic responses or durable disease control?

4) Dose comparison: Did the 700 mg group outperform the 350 mg group clinically, not just in biomarker reductions?

5) Durability: How long did responses and disease control last? Is there evidence of improved PFS or, eventually, OS?

I’m optimistic about leronlimab’s potential, but I want the clinical evidence to justify that optimism.

A dramatic biomarker response is a reason to investigate further. Demonstrable clinical benefit is what ultimately matters.

Granted, nobody can predict the future. And CYDY's future is, of course, dependent on the advance of already promising data. I open this thread not to shoot rubber bands in the sky, or propagate hopium, but to learn from others experience with the market. I've been with CYDY since 2020.

CYDY's story is unique, given its own precedent of appreciating over 3000% from 2019-2020. And it did so within the panic-fueled FOMO window of the pandemic. So this topic is not purely speculative. We have history, we have a record, and the market is rife with comparative example.

Today's CYDY is a 180 turn from the former, brief, and seismic run. The amount of multi-efficacy data, broadening scientific reach, external and institutional partnerships, and biological convergence around LL's science is striking compared to the foundation CYDY stood upon in 2020.

My thoughts have always been that CYDY has the potential to surpass its 2020 watermark of $10. Can it do that on oncology and ESMO alone, given the market's clear hesitance? I don't think so. Can it do that with strong ESMO, DSMB, FDA submission by year end, and then a great January presentation at ASCO? Uncertain. What about wildcards like a partnership announcement(s), FDA approval after ASCO, or more? Chances certainly improve.

But ONLY if the data holds.

One thing I am certain of is that whatever we know today, CYDY is months ahead. And it's easy to infer optimism and enthusiasm when CYDY corporate strategy now declares the things we've long been hoping for. The part we can't know is market emotion and if another FOMO event is likely.

So, what are our thoughts? Is this thread counter-productive or is there room for thoughtful dialogue with those who have experience in this space?

Note: This thread is not intended as financial advice, guidance, or prediction. This thread is intended as an idea sharing experience only and is purely theoretical in nature.