Ilya and Gabriel, thanks again for being here. I thought we could start with a couple of minutes of background on the company and your lead asset, maybe a bit on company formation and where the lead asset came from.
Judah, great to be with you. Thank you for the invitation. Thank you all for joining us today. Immix Biopharma was founded on a simple principle, that we could not accept the fact that the standards of care meant months of suffering with no hope in sight. Gabriel and I asked ourselves the question, can a groundbreaking modality like CAR T be applied outside of cancer? We conducted a global search, and we came across a CAR T that behaved anything but CAR T. With the mild benign tolerability profile, we licensed this technology out of Hadassah Medical Center, and a few years later, we are on the precipice of submitting a BLA in the relapsed refractory AL amyloidosis, where there are no medications that are approved today.
Yeah. Very exciting. Maybe a little bit more about this structure of your CAR T, NXC-201, how that leads to clinical differentiation from other BCMA-directed CAR Ts.
Sure. Our scientist team hailed back from, I guess, one of the cradles of CAR T at NCI, at Dr. Rosenberg's lab. Over the ensuing 20-plus years, they were able to incorporate all the learnings that have been derived from this field and incorporate construct elements that produces distinguishing benign tolerability profile, including CD3 domain, stiffer CD8 hinge region, as well as a proprietary binder domain that combined together into biological filter-like effect that we see in the clinic today, which reduces the non-specific CRS, non-specific activation, and produces the vastly differentiated safety and tolerability profile. Another nuance I want to point out in this case is the unique clinical profile of AL amyloidosis patients, light chain amyloidosis patients.
They actually are unfortunate enough to have a combination of heart and kidney failure present in the same patient. Which presents quite a significant clinical challenge in terms of managing. That is where the CRS duration really comes into play. Our CAR T having a single day, 1-day CRS duration. Significantly reduces the clinical challenge of managing CRS, which is cytokine release syndrome, which is protracted rapid heartbeat, i.e., heart stress, combined with fever, which is dehydration. You have to really manage these patients in an opposite way. For heart failure, you want to take away water, which you can't do because they're getting dehydrated. But you can't hydrate the patient to flush the kidney either. That is why traditionally it has been challenging to apply this modality to these patients. So having 4-8 times longer CRS durations of hours has limited the adoption of this modality.
I guess one of the biggest questions we get is the risk of already commercialized CAR Ts competing in AL amyloidosis. I guess, what can you tell the audience to allay fears that that's coming down the pipe?
Yeah. Despite the breakthrough promise of this technology, it has not made its way into amyloidosis for that very reason, for the duration of CRS that is intrinsic to both approved CAR Ts, which know AL amyloidosis very well, as well as CAR Ts in development. We really lead on the very short and mild CRS.
Okay, great. Then maybe just briefly describe AL amyloidosis, not an indication that everybody's necessarily familiar with, a bit of the epidemiology and the symptomatology, standard of care, unmet need. I think whatever you think would be helpful for background here.
Sure. I'll start with a brief background. AL amyloidosis, light chain amyloidosis, is a devastating rare disease where a patient's own immune system turns against the patient. Normally, plasma cells that reside in our bone marrows produce protective immune molecules called antibodies, which protect us from viruses, bacteria, cancers, et cetera. In this case, plasma cells turn on and they stay on all the time, and they keep producing these toxic antibody fragments, light chains, which circulate all over the body, gum up every vital organ, starting with the heart, kidney, liver, nerves, and others, and patients go into organ failures and pass away from them, starting with heart failure and death. It's a very morbid disease that's difficult to manage.
NXC-201 goes to the source of production and removes the very production source of this toxic, damaging light chains. There's about 5,000 patients in the U.S. being diagnosed on an annual basis. For the longest time, there was only one approval. Clinicians used a combination of a steroid proteasome inhibitor and chemotherapy, actually a mustard gas derivative cyclophosphamide for decades. Then in 2021, DARZALEX of Johnson & Johnson completed a trial, and that was approved as a four-drug combination, which produces approximately 50% complete response. Half the patients, unfortunately, require immediate second-line therapy, with a third progressing over the ensuing years, adding to that, so approximately two-thirds of patients overall will require subsequent therapy. Once this four-drug combination stops working, there is no approved therapy then clinicians reach for investigator's choice, which means just reshuffling based on the recent side effects and in hopes of some benefit.
You mentioned this 5,000 patients diagnosed annually number. Do you think diagnosis rates could improve as next-gen therapies make their way to patients?
We believe that very clearly that just like in ATTR, when impactful effective medicines became available, the impetus for diagnosis skyrocketed because there's much greater awareness. We believe the same thing is taking place in amyloidosis. Further to build on that, in order to diagnose ATTR, clinicians have to order blood tests to rule out presence of light chain amyloidosis. Our incidence has been rising in parallel with those of ATTR cases.
You're running your registrational phase II NEXICART-2 study. In second line relapsed/refractory AL amyloidosis. Maybe give us a high-level description of the data you've collected and presented to the public this far. How has it evolved, maybe from ASCO last year to ASH this year? I want to make sure we touch on CRS and time to response, as those are clearly important in the conversation.
Judah, as you point out, with the hindsight of increased follow-up, we've seen our complete response rates improve from ASCO at 70% to 75% at ASH, and then even higher with our most recent update, driven by the biology of this disease. We're reporting the entire set, obviously the top-line data for the entire set of 45 patients later this month, both efficacy and safety. The tolerability continues to be very consistent. We've reported that the CRS is very consistent and manageable, just like low grade. And median duration, one day.
Right.
Correct.
Right. Then just on time to response, I think that is something that investors are paying particularly close attention to. What have you seen in the data thus far? Do you think that is a prognosticator of what we are going to see going forward as well?
We have shared to date that responses to NXC-201 have been rapid and deep. Why that is important, deep and rapid responses in this disease predict organ responses, which subsequently predict survival. Yeah. That has been extremely important to all investigators.
Okay. Then you mentioned the improvement in complete response rate from ASCO to ASH, but maybe just help the folks in the room with an idea of how the data were received at ASH beyond CR rate. What has been the focus for KOLs within the data?
The first question by the hematologist who was chairing the session was, "Why aren't we dosing anything else in this disease?" That's an unofficial. This is just I'm just reporting what I heard. KOLs are thrilled, right? Because I think it presents a welcome alternative to the sub 10% complete response rates we're getting now at the expense of repeat dosing with the attendant adverse side effects.
Okay.
This is the liberating therapy. Not my term. Our PIs actually use that term.
Okay, great. Just general feedback from docs on neutropenia and thrombocytopenia, how are they thinking about the AE profile here?
Specifically to those very expected, manageable, and shorter than expected, if anything, with no clinical implications.
Okay, great. Like you said, you have a readout coming in late September, which will represent the full registrational population. Like you said, 45 patients. A couple questions here. I guess for the newly enrolled patients, which I believe is about 20, what will their average follow-up look like compared to the initial 20 patients?
Correct. For the latest set of 25 patients
25.
The follow-up will be approximate but slightly shorter than ASCO and ASH patient group of 20. KOLs would be excited. They are telling us to get what they are used to now, 70%-75%, which would be clinically meaningful for them and very impactful. Certainly an improvement over the 10% that they are used to now.
Okay. You are characterizing the readout as top line.
Correct.
How are you thinking about breaking out duration of follow-up in the data communication? I guess that's a common question we get, data presentation within the context of a top line.
Correct. As we've marched through the data and monitoring the response timeline, we know that it takes up to one year to fully manifest. Just due to the definition of how CR is defined in this disease. Stay tuned for the latest update.
Okay. That is helpful. Maybe just tie again, like that 70%-75% CR rate with the 95% CR rate we have seen in the latest data cut of the initial 20 or so patients. In your mind, are investors primed to understand that duration of follow-up will factor into that CR rate potentially being lower than the 90%, 95% that everyone got so excited about?
While we try to illuminate the biology involved, stay tuned for the very specific answer later this month.
Okay. It is fair.
A great question.
A good commercial.
A great question.
Now, you initially were going to submit a BLA following the update later this month. You are now waiting until, and correct me if I am wrong, you are waiting until you have one-year follow-up data in all patients, which should be March of next year. Just help us with the thought process behind that. What were the interactions, whether it was with your board, with regulators, that informed that decision?
All right. Given that the biology of the disease has told us that it takes up to one year to manifest full magnitude of CRs. We want to take the mathematics weighted out of this. We want to be very clear when we submit our package. It has to be clear and not short-change the magnitude of the benefit that this provides. We don't short-change clinicians, stakeholders, and patients who put their trust in this.
Okay, that makes a lot of sense.
Single motivator.
Just from a regulatory perspective, remind us of what interactions have been thus far that support your understanding of the agency believing that the unmet need is as high as it is here. What's the latest thinking on potential review and subsequently launch timing?
We think that the unmet need magnitude that you mentioned is highlighted and underscored by the RMAT, Regenerative Medicine Advanced Therapy designation that was awarded to us, followed by Breakthrough Therapy designation upon further examination of the data, and Orphan Drug Designation. We believe that there is a similar motivation to advance this therapy and give this to patients. Understanding this urgency, we have onboarded a chief commercial officer to keep the processes moving and onboarded the head of market access, market ops et cetera, to really facilitate the process of transitioning from the clinical domain to getting this into the hands of clinicians. Then patients, obviously.
Okay. That's helpful. So it sounds, review could potentially be fairly rapid.
We believe that it'll be, yeah, accelerated.
Okay. That makes sense. Maybe just taking a step back to the competitive landscape and discussing that a bit further, the space is developing like multiple myeloma, where CAR T is currently ahead, but bispecifics are slowly catching up or becoming more important in the conversation. What are you seeing from bispecific efforts in terms of safety and efficacy, and how would you say they compare to NXC-201?
Awesome.
Did you want to go or
Great. Thanks.
Yeah.
Awesome. Great to be here today as well, Judah. Making progress here. Compared to these other therapies in development, we do acknowledge that AbbVie and Regeneron behind them are developing bispecifics. Three points. Number one, our registrational trial is ahead of these folks. Number two, we believe our clinical is superior. We are a fifth-line therapy versus their second or third. We have an independent review committee evaluating complete responses. We have more frequent, deeper, and rapid organ responses. These bispecific therapies are consistent with data and other indications, produce a repeat challenging immunosuppression, which results in, so far in these studies, a 70%-80% infection rate. We do not have that problem.
Right.
We believe clinical is superior, point number 2, and point number 3, ladies and gentlemen, we are able to do all of this in 24 hours, not 24 months. These therapies are all specced up to dose for monthly for up to 2 years. Given our duration of response that we've seen so far, which has been measured in years, we believe that if we assume that all these drugs were on the market today, Judah, after NXC-201 gets to patients, there may not be much of an unmet medical need left for these therapies.
Do you get the sense that both patients and providers kind of appreciate this risk-benefit profile for a CAR T versus bispecific, and tie in quality of life measures as well? What are you hearing from stakeholders within the AL amyloidosis community?
Correct. Beyond the immunosuppression that produces the 80% infection rates that you see in both the two AbbVie and Regeneron trials. In addition, if we look at historical data, there's an up to 30-plus percent chance of hospitalization due to these side effects, which is definitely not fun. Until we believe that one and done liberating NXC-201 experience is certainly great for patients and doctors, and certain folks in our trial and otherwise have been able to talk about that in certain contexts. For folks who have this four-drug combo and just assume that they're going to be at the hospital for the foreseeable future to travel for the first time in years or decades can be a liberating experience.
I guess maybe going back to that myeloma analogy, how important is community physician adoption? Or said another way, what's your sense of the proportion of AL amyloidosis patients that can be penetrated by CAR T centers as opposed to necessarily being treated in the community? That interplay of site of treatment, how do you see that working out in this indication?
Yep. Very good. Maybe Dr. Rachman if you can comment on how folks are diagnosed and whether they end up at tertiary centers, and I can wrap up this one after that.
Yeah, sure. What's happening now as we follow a patient journey, patients usually present with a very vague non-specific symptom, shortness of breath, fatigue. Clinicians very quickly send them either to a cardiology specialist or a kidney specialist who looks at some imaging data, and they say, "Look, there's some thickening, there's something vague." Eventually gets diagnosed, either because they want to rule out ATTR, and they send off AL tests. Those come back positive, and they immediately get routed to a hematologist.
Right.
That's the typical patient journey. Unfortunately, it takes much longer than it has to, but that's typically how that flows.
Yep. I'd add that by the time to build on that those patients at that point are at the centers that are the AL referral centers, which are also centers that are capable of, today, of dosing a therapy like ours. We have a specific plan, as Dr. Rachman mentioned, a chief commercial officer in place, as well as head of market access marketing. We also have medical affairs and sales ops already in place as we roll that out to those select, let's call it 60 or so centers that we are targeting at this point.
Okay. Just based on kind of the epidemiology of the disease, it seems like the vast majority of patients could be treated at CAR T centers. I guess i f bispecifics and your CAR T is approved here, do you have a view on what the eventual split in the market could be, and what would be driving factors? Maybe we start specifically with the second-line relapsed refractory setting.
Yep. So, two points there. The first point is based on public information, if we look at the evolution of where these type of therapies, CAR Ts, have been dosed, they increasingly are migrating from the hospital to facilities near or sometimes not near once clinicians get familiar with how to dose them and get familiarity. When we compare our tolerability data today with the tolerability data of some of these other therapies, we believe that we are in a favorable position to foreshadow access to this therapy even beyond the traditional tertiary centers.
Second point is, there are three letters that make a big difference here. Duration of response, DOR. So far, our median of duration of response, DOR, has not yet been reached at all. We believe that patients, and we've seen in our trial, are willing to go to those centers to experience a shot at having a multi-year remission. Being away from the hospital. We believe that there's a significant opportunity here, and we think that our colleagues. When we started on this journey, we were one of the few companies that was focused on AL amyloidosis. I think today we're still one of the few independent names focused on it. We can see that the likes of Big Pharma moving into the space, we believe, validates the opportunity.
Is there any reason to think that the split in frontline treatment for a CAR T versus bispecific could be different than second line?
I don't think so. I think with our upcoming launch soon to demonstrate the head-to-head
Right.
What we can do versus the four-drug combo. We believe that NXC-201 promise to capture the vast majority of patients with one and done in the front line as well will be realized.
Okay.
To build on that, split is an interesting concept. Certainly when we are selling widgets and I Phones. There is certainly market share that plays into it. Here, there is a pretty clear goal. We are looking to, as Dr. Rachman mentioned, the immune system has turned against these folks. There is a toxic fountain of junk being produced. We want to silence that, the source of that toxic junk, and return folks' levels to normal, which follows with organs responding and the bone marrow clearing up and patients being able to breathe easy and return to their normal lives. In the front line as well, if we are able to achieve those goals, and we believe that there is a significant portion of patients here which will experience extended remissions. That will play out certainly where the fifth line therapy, we were able to produce these remarkable responses
Right
so far, 19 out of 20. The vast majority of those patients continue to experience that complete response. Everybody, no one has come out of complete response yet. We are hopeful that in the front line, folks will choose the one and done as well.
Right. Yeah.
Dr. Rachman touched on cyclophosphamide is literally a derivative of mustard gas. It's time that the promise of cell therapy becomes real. And that we are able to produce the efficacy without the toxicity.
Okay. Maybe just a little bit deeper on that frontline opportunity. That is a relatively recent announcement from you guys on initiating a phase III study in frontline AL amyloidosis. Maybe just talk us through that business decision and this study rationale and what you would be hoping to see in terms of efficacy.
Yeah. It is a head-to-head trial versus the four-drug combination, which includes that chemotherapy. The primary is a complete response rate. The same endpoint that powered the approved drug in the space, the first approval, as well as the same endpoint we have in our existing trial. We believe that we are in a great position when it comes to powering that endpoint. As Dr. Rachman mentioned, the first question after our presentation at ASH was why this is not available. In the front line, right? At the end of the day, we're putting an option. Folks today with this disease go into the supermarket, and there's one bottle that contains four drugs, and t he shelves are empty.
Right.
Right? At the end of the day, for either relapse patients or folks who find themselves diagnosed for the first time, it's an option that we think folks will be compelling.
Can you just remind us of the competitive landscape in frontline? What does competition look like here, and what are timelines between you and competitors in frontline specifically?
Yeah. So as we believe a leader in this space, we were the first company to get out there with documents and what is required to kick off this frontline trial. Last month, AbbVie in fact, literally last week of August, we believe, did disclose their trial on clinicaltrials.gov. We are in good company. At the same time these other folks, let's assume other companies launched their frontline trials, there is only one one-and-done option. For the frontline, so we believe that we will continue to stand out and that our results will stand up. Anything to add to that?
Look, it's great to see such innovation enter the space where we're still administering mustard gas. It's a welcome sort of reawakening of the field, so it's nice to see reinvigoration of efforts. We welcome additional options for patients, but I think it's time that we could effect substantive innovation.
Okay, great. Maybe just remind us what you said about the potential for pursuing additional indications. What could timelines to announcement of those indications be? Anything you would highlight? Any area of development we should be thinking about?
Yep. On that, for sure, to build on Dr. Rachman's earlier comment, We have got to stay tuned. Stay tuned. We are laser-focused on completing these AL amyloidosis, giving patients a second option as the possible second approved drug in 100 years for this disease, which is now certainly a deadly and devastating disease. In addition, with Dr. Rachman at the scientific helm here, we continue to believe that there are select opportunities to be thoughtful to apply a friendly CAR T i n indications where it can make a difference. Certainly, recent events at Big Pharm as well, we believe, highlight the advantages.
Okay, great. Then maybe just rounding out the company-specific questions. Cash runway guidance, operational activities, between the potential commercialization in second line, then the phase III in the frontline, what is funded with the cash you have on hand now?
Correct. We have cash on hand to fund all the activities we have covered today, which includes relapse refractory NEXICART-2, BLA submission, and commercial launch, all the way through mid-2028, assuming no revenue at all. And also funding the frontline trial.
Got it. Great. In the last few minutes here, we are just going to run through a mini-survey that we are asking all the biotech management teams at the conference. Lightning round. The first question is on China's rise in biotech innovation. How are you thinking about competitive position here? Will this influence your R&D and/or business development strategy in any way?
Nope.
Has not affected us to date.
Okay.
That is the answer.
Okay. That's helpful. I guess, anything coming down the CAR T development pipe in China that keeps you up at night? Or you guys seem to be fine.
We're clearly following, but not for AL amyloidosis.
Okay. Makes a lot of sense.
Certainly we've, since we've started this journey several years ago, we've inspired a lot of folks to move into the space. We don't see any commercial competition.
Okay, great. The next topic is AI. How is Immix leveraging AI or thinking about AI's potential disruption of your space in any way?
Disruption, we find that these trials, and Dr. Rachman says internally, it's just another barrier that AL amyloidosis is throwing at us, right? There's a lot to it. While AI, AGI may be very smart, we don't see an immediate threat due to developing anything that would be superior to what we have.
Okay.
Of course, there are many reasons for that, the complexity of biology, et cetera. Nothing more to add there.
Okay, great. Just the last one is just on the regulatory front. Just between changes at FDA, which seem to be constant, although it seems like maybe we're settling in a little bit here. Pricing, which is maybe slightly less relevant for you guys, tariffs, anything on the regulatory front that kind of keeps you up at night or takes up a lot of your attention?
Look, to build on that, look, having lived through a pandemic, government shutdown.
Yeah
Correct. Some things are changing. Look, resting on clinical fundamentals and precedents that every single BCMA CAR T has been approved, and its trials are similar to ours. Rare orphan deadly disease with nothing approved, with RMAT Breakthrough Therapy designation, clinical data that we have, we believe we're in a good position based on the fundamentals that dictate validity of the effort.
Okay. Great. All right. I think with that, we can call it. Thank you again for being here, guys. It was great.
It was great to be with you today.
Yeah. Thank you.
Awesome. Wonderful.
Okay. Thank you.