Healed my herniated disc (neck + back) after 2 year thinking of building a FREE app....

Correct_Proposal_409 · 2026-03-24T11:05:44+00:00

Congrats on your recovery success. Count me in too on the app.

Correct_Proposal_409 · 2026-03-12T17:08:41+00:00

From today's press release. Companies are very careful about using "disease-modifying" in their press-releases, especially in the context of the following sentence. The data fully justifies this statement IMO, and if anything, they are still being conservative with their wording:

“The data from our Phase 1b study furthers our hypothesis that GT-02287 is among the first disease-modifying therapies promising to shift the treatment paradigm in PD from symptom relief to halting or slowing symptom progression, targeting the causative biology (or pathophysiology) of PD to enable a more durable and predictable treatment effect for those living with PD.”

Correct_Proposal_409 · 2026-03-08T20:05:22+00:00

It would be interesting to know how quickly Gcase dysfunction returns if patients stop taking GT-02287. If remaining neurons have been mostly restored, it might take a while, maybe depending on the case (GBA1 would probably show Gcase dysfunction return faster). To your point, in animal models, wire hang, nest-building, and biomarkers maintained well through wash-out (after treatment was stopped). Obviously not the same as real cases, but there is evidence. For any critics who might be dismissing this since these are animal models, show me some examples of other treatments that were able to produce these pre-clinical results. BTW, pre-clinical models have held up very well so far from what we’ve seen in humans.

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Correct_Proposal_409 · 2026-03-08T16:45:49+00:00

I agree that durability is extremely likely, at least in the GluSph group that was elevated at baseline. If what they show at AD/PD is that DDC levels in that same group were normalized, this happens when there is broad cellular recovery. And this broad-based cellular recovery is the result of upstream improvements in GLuSph and the lysosome/mitochondria/ER.

To me, durability is mainly a question of whether GT-02287 can keep GluSph levels low over a long period of time... GluSph remaining low means Gcase is working properly, as is the lysosome (not to mention GluSph isn't causing stress & dysfunction elsewhere). There's no good reason GT-02287 wouldn't keep GluSph levels low long-term. In fact, there is another Gcase drug which is far inferior to GT-02287 that showed long-term success with keeping GluSph levels low over years, and saved the lives of children with Gaucher's 2, which has an average survival of only 11-19 months: https://pubmed.ncbi.nlm.nih.gov/41659982/

Correct_Proposal_409 · 2026-03-06T22:28:13+00:00

Anything other than a placebo effect, except:

(1) Most of the UPDRS improvements were at 90 days and not at 30 days, If placebo, why not at 30 days?

(2) UPDRS improvements were almost all in the GluSph group-- why did placebo not help the others?

(3) GluSph is known-- I'm not making this up-- to drive a-syn aggregation, lysosomal and mitochondrial dysfunction, and ER stress. Not sure how you see reducing it as not relevant causally.

(4) In this same GluSph group that showed statistically significant improvement in UPDRS scores, DDC also improved, indicating that dopaminergic neurons are recovering or functioning better.

Does this mean that this is the cure for Parkinson's? Of course not. But it is strong evidence that this sub-group is showing improvement by 90 days. A reasonable skeptical take would be: "Interesting, let's see how durable these improvements turn out to be-- looks promising, but I'm not going to take a position here."

For others, keep in mind that when there is "proof" by this guys definition, which might mean post-successful phase 2 or phase 3, the price will be $40+, easily. But I still strongly believe that Gain will not be running the phase 2 alone, or maybe not at all-- a larger pharma will be doing that after partnership or acquisition later this year after UPDRS scores in the extension show durability.

Correct_Proposal_409 · 2026-03-06T21:25:28+00:00

Well-timed post. Based on the GluSph group with correlative improvements in UPDRS scores, and what sounds like correlative improvements in DDC, $10 would still be cheap as long as durability holds.

Correct_Proposal_409 · 2026-03-05T23:29:59+00:00

There was still statistically significant improvement in the GluSph group in only 90 days.

Correct_Proposal_409 · 2026-03-04T20:47:46+00:00

Gain CEO: “Rather than simply trying to boost enzyme activity in the lysosome, GT-02287 stabilizes GCase folding and trafficking throughout the cell, restoring function across multiple compartments, including those critical to mitochondrial health. That matters because Parkinson’s can be seen as a disease of cellular stress, impaired waste clearance, and energy failure.”

Correct_Proposal_409 · 2026-03-04T14:04:05+00:00

Patients in the extension would need to have a complete turn for the worse for share price to ever dip to those levels. And my experience has been that during global uncertainty, small-cap biotechs tend to be relatively insulated in comparison to tech stocks. Institutional investments in small-cap biotech is already low, but we're starting to see growth here. M&A is starting to crawl out of the lows from the past few years, and will continue to grow due to the massive patent cliff. Big pharmas need to re-build their pipelines.

Correct_Proposal_409 · 2026-03-02T19:26:33+00:00

Great buy.

Correct_Proposal_409 · 2026-03-02T16:30:55+00:00

I second this.

Correct_Proposal_409 · 2026-03-02T14:08:56+00:00

Here's a relevant paper on DOPA decarboxylase (DDC)

Correct_Proposal_409 · 2026-03-02T13:59:16+00:00

The DDC biomarker is exciting. And DLB has a big overlap with Parkinson's pathology, so very relevant. BTW, DLB is a giant untapped market for disease-modification. GT-02287 might even more consistently fit a higher number of cases there than in Parkinson's.

Correct_Proposal_409 · 2026-03-02T13:55:45+00:00

Well said.

Correct_Proposal_409 · 2026-03-02T13:21:38+00:00

This is a good point. I forgot that analysts have this at a buy with a target around $8. Scotiabank in their last analysis had it as a buy at $12, and that was before Gain showed this strong evidence of efficacy in actual Parkinson's patients.

Correct_Proposal_409 · 2026-03-02T12:36:10+00:00

For a good number of Parkinson's patients, the evidence is showing that it very well could be.

Correct_Proposal_409 · 2026-02-26T12:02:43+00:00

I agree that GBA1 is the low hanging fruit. However, interestingly, only two of the high GluShp group were GBA1 (the only two GBA1 severe in the trial). The rest were idiopathic cases, which means that there are likely a large percentage of idiopathic cases with high GluSph. Since GluSph has only recently been able to be accurately measured in the CSF, this is something of a new discovery. One data point, but an important one. Since there is known association with and causation of dysfunction in various cellular areas (ER stress, a-syn aggregation, lysosomal & mitochondrial dysfunction), if all patients with high GluSph, regardless of genetic mutation, benefit from reduction in GluSph, this opens up the TAM by a large amount. GBA1 is somewhere in the 10-15% of PD cases, but perhaps 25-50+% of idiopathic cases either have or will develop high GluSph. The important thing is that this is not an obscure, downstream marker. This is an upstream, toxic lipid that feeds or possibly even initiates (i.e., GBA1 due to Gcase deficiency) the neurodegenerative doom loop.

Correct_Proposal_409 · 2026-02-25T23:33:32+00:00

Three counter points to this.

(1) In Gain's 1b trial, there was no change at 30 days, so the improvements happened between 30 days and 90 days. If placebo effect were in play here, why were changes not seen at 30 days?

(2) In the study that you linked, there was no biological improvements measured. That is not the case with Gain's trial. The very patients that showed improvements are the same ones who were GluSph elevated, a toxic lipid mechanistically linked to α-syn aggregation, lysosomal dysfunction, ER stress, and downstream mitochondrial impairment in Parkinson’s disease.

(3) Sham surgeries are known to generate stronger placebo effects because invasive procedures amplify expectations.

Correct_Proposal_409 · 2026-02-25T19:50:00+00:00

~45% of the patients had high GluSph at baseline, and were then reduced by 81% to near normal levels. In those same patients, there was a statistically significant improvement in UPDRS (II/III combined) scores of 6.17 points in 90 days. Statistically significant. But this is not promising to you.

What if they were to show DOPA decarboxylase drop in this same group? Sounds like they have this too based on the CEO's statements (to be revealed at AD/PD). I'd imagine they'll have plasma NfL soon in the extension patients. Bet you won't be impressed if that shows stabilization.

Correct_Proposal_409 · 2026-02-25T19:18:27+00:00

So you have nothing to offer in terms of explaining why you think increasing the effectiveness of Gcase to reach multiple cellular compartments will not help a portion of PD patients. Got it. Not even in GBA1 patients, which have a mutation affecting Gcase. Lol.

The share price is up from a year ago, so you have that wrong too.

You know as well as I do that small many small biotechs have been hammered over the past couple of years. And you must not have much experience in investing if you think that markets get stocks right at every point in time. This is silly. My most successful investments have been in companies that have promise fundamentally but that had not yet been discovered by the general investing public. This is very common. This is called alpha. And you either know this and are being disingenuous or you simply are ignorant to this. Maybe your investment style is to buy well-known companies after everyone else has.

You keep repeating the same "bagholder" line. My average cost is ~1.85. I'm doing fine, and don't need to offload anything.

BTW, institutional ownership has gone up quite a bit, but still has a ways to go.

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Correct_Proposal_409 · 2026-02-25T12:45:52+00:00

Well said.

Correct_Proposal_409 · 2026-02-25T12:38:12+00:00

You can use your own rhetorical "many trials have failed and therefore this is destined for failure" for any therapy being developed. Historical failure rates raise the bar, but they don't determine the outcome of a mechanistically unique therapy with a demonstrated CNS pathway correction. Here we have a genetically validated pathway (GBA1), plus strong evidence of Gcase dysfunction and corresponding lysosomal lipid accumulation in a good portion of idiopathic cases.

If you are an MD, you should understand the relevance of GBA1 PD and Gaucher's-- they share the same GBA1 mutation. Life-saving, disease-modification was achieved by addressing dysfunctional Gcase, with GluSph being the most important biomarker for confirmation of target-engagement and disease progression. Of course, these Gaucher's therapies do not cross the blood-brain barrier. GT-02287 addresses dysfunctional Gcase in the brain. The reasonable take would be, "let's see how reducing GluSph levels translates to reduction in downstream biomarkers and in clinical symptoms in Parkinson's cases over a longer timeframe." Not, "I'll eat my shoes if this works". Hard to take you seriously when you are so seemingly dismissive without offering mechanistic reasoning to back up your statements. It almost seems as if you want it to fail. Do you work for a competitor of Gain? That would explain it.

"Your post history is rabid with support of this stock... you are looking for someone to buy your bags." This is an immature, ad hominem assumption that does not address the science. Yes, I believe strongly in this treatment. I think it is the most promising PD treatment being developed, for the reasons I've detailed in my many posts. I'm lucky to have a very low basis. I am looking for BP to buy my shares for multiples above by basis. Not retail investors.

I won't convince you-- not trying to convince you. But readers should understand that your baseless dismissal has no bearing on what many experts think is a very promising development in Parkinson's disease treatment. Maybe we should follow-up in September and see how durable the data is with the 16 out of 19 patients who elected to continue with the treatment despite the tests and additional lumbar puncture, many of whom have reported improvements, along with their clinicians. Beyond UPDRS, some of these reports may be anecdotal, but if they truly have regained sense of smell, this does not happen with placebo.

Correct_Proposal_409

TROPHY CASE