From a clinician's perspective, how has the shift towards subcutaneous routes evolved and what unmet burdens remained even with standard sub-Q options?

This is an excellent question, and thanks for bringing up that very important historical perspective.

Because you're right, the large volume intravenous drug is how these monoclonal antibodies started.

And in fact, I would say it was not even just 75 minutes, the first infusion of the first approved monoclonal antibody, CD3D monoclonal antibody used to take about eight hours on day one.

And it went from eight hours to then four hours to then three hours to an hour and a half, et cetera.

So you can imagine, yes, over time, a lot of improvement has happened.

But when the subcutaneous administration came, which was a huge jump forward because the patients did not have to go through any intravenous, they did not have to sometimes get admitted to the hospital because of reactions, et cetera, because the subcutaneous administration was significantly safer, of course, much more efficient, less time for the patient in the chair, and more convenient, better for workflows, better for the health care system, the institutions, et cetera.

Dr. Alawadi, as principal investigator of the Phase III Aroclia trial, can you walk us through the design comparing sub-Q esotuximab via on-body injector to IV esotuximab? And specifically, how did the 71.1% versus 70.5% overall response rates and the steady state concentration geometric mean ratio of 1.532 confirm efficacy and pharmacokinetic non-inferiority?

What's the feasibility of expanding at-home administration pathways and what clinical protocols must remain in place?

I think this is the most exciting part of the study, in my mind, is the possibility of doing at-home administration.

Now, the protocol allowed that for patients after the first six cycles, so the patients had already gone through the primary objective of the efficacy and the pharmacokinetic prior to that time point.

But it was a patient preference.

And when eventually the study got completed, there was only a small number of patients who went through the at-home administration, and all of these were ex-US.

So none of the US patients got to that point or opted for it, et cetera.

The protocol outlined very nicely what checks and balances had to be in place so that, in my opinion, if somebody has to go down that path, my understanding is that more physicians, more healthcare systems outside the US, especially in Europe, are considering that strongly, basically, because they already have some of that process for certain other drugs, like bortezomib for multiple myeloma.

And so hopefully that adds to the benefit and a more positive experience when you're also dealing with this cancer journey.

I want to reiterate something that Beth brought up very appropriately is that we talk about the patient experience side of it, which clearly is more positive because the patient has never seen an exposed needle.

When the disc is going on, there's no exposed needle.

When the disc is coming off, there's no exposed needle.

The needle is always inside the disc itself.

The only time the needle protrudes is when the disc is on the body and the button is pressed, etc.

So those things are very important.

And because of the way that we're conditioning our society to using these drugs, I think patients will be more receptive to these types of drugs.

From a clinician's perspective, how has the shift towards subcutaneous routes evolved and what unmet burdens remained even with standard sub-Q options?

This is an excellent question, and thanks for bringing up that very important historical perspective.

Because you're right, the large volume intravenous drug is how these monoclonal antibodies started.

And in fact, I would say it was not even just 75 minutes.

The first infusion... of the first approved CD3D monoclonal antibody used to take about eight hours on day one.

And it went from eight hours to then four hours to then three hours to an hour and a half.

et cetera.

Dr. Alawadi, as principal investigator of the Phase III Aroclia trial, can you walk us through the design comparing sub-Q esotuximab via on-body injector to IV esotuximab? And specifically, how did the 71.1% versus 70.5% overall response rates and the steady state concentration geometric mean ratio of 1.532 confirm efficacy and pharmacokinetic non-inferiority?

So tell us about this drug Sarclisa and what does the FDA approval of the new variety of this called Sarclisa Acena add for patients and healthcare providers?

So, Dr. Seichert, sarclisa or esotuximab belongs to an important class of drugs in myeloma, which is called CD38 monoclonal antibodies.

There is one other drug available called dartumumab or Darzalex, and sarclisa or esotuximab is another agent available here.

These are very important drugs.

So, sarclisa is available for the treatment of newly diagnosed patients in a combination called esatuximab, bortezomib, Lendex, or esavrd.

It is also FDA approved for patients with relapse refractory disease in two specific combinations called esapomalidomide dex or esapomdi or esacarfilzomib dex or esakadi.

Now, while by itself esatuximab or sarclisa has really provided benefit to patients both in the newly diagnosed and relapse setting, this particular FDA approval this year is for the availability of esotuximab or Sarclisa in a subcutaneous formulation.

And it sounds like this takes up less time of the nurse or doctor or whoever the healthcare provider is who's administering the drug?

And so with that, I'll transition over to Sikander to talk about transplant-ineligible now, um, who are a very different population, often older, often frailer, multiple comorbidities, and how are we really approaching those patients and what is becoming standard of care.

Thanks a lot, uh, Nisha.

Thanks for, um, uh, setting us up so well with this initial portion about the transplant-eligible.

So I'll, um, walk us through some of the data around transplant-ineligible patients, which is also a very important component of the landscape of myeloma treatment, where, uh, the average age is somewhere about seventy years, and the patients can have their own comorbidities.

So the first trial over here is the Phase 3 Cepheus trial, which was for patients that were transplant deferred.

I do wanna clarify that ineligible could be that they just cannot receive it, or in today's day and age, the patients could be, um, potentially deciding not to, uh, undergo the transplant.

So how this study was, um, uh, set up was that the key eligibility criteria were transplant, uh, either ineligible or those who decided to defer.

So, uh, in addition to these immunotherapies that have recently been approved in the second line, uh, Sikander, perhaps what trials are we expecting, um, uh, more data, uh, in the upcoming years? What is exciting you the most?