Clinical readouts support NXC-201’s potential in ALA

While still in the early stages, we are encouraged by the initial data from the US NEXICART-2 trial (normalized disease markers for all four patients within 30 days of treatment and 2/4 patients achieving a complete response (CR)), which mirror the updated data (12/16 patients achieving CR) from the NEXICART-1 trial in Israel. Notably, the safety profile remains favorable, which differentiates NXC-201 from other approved CAR-T therapies and is a key consideration given the multi-organ involvement and fragility of relapsed/refractory amyloid light chain amyloidosis (r/r ALA) patients. The strategic priority is now NEXICART-2, and with recruitment expected to accelerate from Q125 management is confident in delivering top-line results in mid-2026, which will likely be followed by a regulatory application to the FDA (in H127, according to our estimate) if the results are supportive.

Upside opportunities beyond ALA

In addition to ALA, Immix plans to explore NXC-201’s utility in other autoimmune indications in Q425 (with interim clinical data supporting this choice anticipated), an area where CAR-T therapy is believed to hold potential, although no treatments are currently approved. Our updated valuation does not include contributions from this opportunity, which may add to the upside potential.

Valuation: $125.8m or $4.6 per share

We value Immix at $125.8m or $4.6/share ($123.1m or $4.5m/share previously), using a risk-adjusted net present value (rNPV) approach, driven primarily by its lead program, NXC-201 in ALA. We assume a probability of success (PoS) of 30%, a 2028 launch and peak sales of c $520m.

Investment summary

Company description: Patient-prioritized approach to CAR-T

Immix is a clinical-stage biopharma focused on developing the first outpatient CAR-T therapy for r/r ALA, a rare and debilitating condition characterized by a fragile patient population with limited treatment options. Lead candidate NXC-201 is a B-cell maturation antigen (BCMA)-targeting CAR-T that has demonstrated encouraging clinical trial results in multiple myeloma (MM) and ALA, with the company deciding to exclusively focus on ALA in 2024. It has shown a favorable safety profile (no neurotoxicity and only low-duration cases of cytokine release syndrome (CRS)), showing promise to address common side effects associated with current CAR-Ts alongside limitations related to hospitalization costs and access. The Israel-based NEXICART-1 trial has reported data for 16 r/r ALA patients with favorable safety and efficacy. Immix recently commenced the US-based NEXICART-2 trial (six patients dosed to date), where management aims to replicate the favorable results seen so far. Interim results from the trial are expected in mid-2025, with top-line data expected in mid-2026. Immix has also communicated plans to expand NXC-201 to additional autoimmune indications by end-2025. Given the focus on NXC-201, we believe that development activity on legacy asset IMX-110 has been put on hold and management is in the process of organizing data from clinical activity to date, with the likely goal to explore strategic options, including out-licensing

Valuation: $4.6 per share, with further upside optionality

We value Immix Biopharma at $125.8m or $4.6 per share, primarily based on a rNPV calculation for NXC-201 focusing exclusively on r/r ALA. Following the recent clinical progress and increased visibility on development plans and trial timelines, we have revised our estimate for peak sales for NXC-201 in r/r ALA to $520m ($347m previously) and PoS to 30% (25% previously). We continue to expect a launch in 2028 with peak sales achieved in 2034. We assume a licensing deal in 2027 worth $500m, including an upfront payment of $50m and 15% royalties. We also remove NXC-201 in MM from our valuation following its deprioritization and adjust our assumptions for IMX-110 (pushing out the launch timeline and reducing PoS across the two target indications).

Financials: Cash runway into Q425

Being pre-revenue, Immix has been funding its development activities through external capital. Since listing in December 2021, the company has raised $53m in net proceeds (including $21.6m net from the IPO). For 9M24, it reported an operating loss of $17.7m, of which c 56% was related to R&D expenses ($9.9m), which rose significantly (+76% y-o-y) following the initiation of the US-focused NEXICART-2 trial in mid-2024. The end-Q324 net cash position was $19.7m (no debt on the books) and we expect this along with another $8m in grant income from the California Institute for Regenerative Medicine (CIRM) from November 2024 to provide runway into Q425.

Sensitivities: Typical risks for a CAR-T-focused biotech

Immix is subject to the usual biotech risks associated with drug development. It is sensitive to clinical development delays or failures, regulatory outcomes, competitor successes, partnering setbacks, financing and commercial risks. A key risk for Immix is its current reliance on a single program (NXC-201 in r/r ALA), which exposes its outlook to binary events (success or failure of the clinical trial), though management intends to pursue other autoimmune indications, which may mitigate some of this risk. Another key sensitivity is its focus on CAR-Ts, which have been under regulatory scrutiny recently due to risks of secondary malignancies, although there is ample evidence suggesting that the benefits outweigh these risks. An important medium-term milestone will be whether the US-based NEXICART-2 trial will replicate the encouraging results seen in the Israel-based NEXICART-1 trial. The next update (an interim readout) is expected in mid-2025.

Scalable pipeline with autoimmune CAR-T focus

Immix’s clinical development strategy is currently focused on the design of innovative therapies for immune-mediated indications, with ALA being the primary indication (Exhibit 1), following the company’s decision to prioritize ALA over MM in 2024. Lead asset NXC-201 is a sterically- optimized BCMA-targeting CAR-T asset which, given its robust safety profile demonstrated to date in clinical trials (no neurotoxicity and manageable CRS), is showing promise to potentially become the first outpatient CAR-T therapy. This would lead to significant hospitalization resource and cost savings compared to currently approved CAR-T therapies, in our view. The asset was in-licensed by the company’s now wholly owned subsidiary Nexcella in December 2022. To our knowledge, NXC-201 is the only CAR-T in development for ALA, a rare, plasma-cell-related disease (annual incidence of c 4,000 cases in the US) caused by the abnormal build-up of amyloid proteins in tissues and organs (with the heart, kidneys and liver being the most affected). Despite recent advancements, c 75% of patients are refractory to frontline treatment (daratumumab with cyclophosphamide, bortezomib and dexamethasone or relapse, and there are no approved effective treatments in the r/r setting.

Immix believes that with its favorable safety profile, alongside its potential to improve survival outcomes for challenging diseases, NXC-201 offers advantages over current approved CAR-Ts. While the Israel-based NEXICART-1 trial generated encouraging results in both ALA and MM patient populations, Immix is now focused on the US-based NEXICART-2 trial in ALA. A key objective of this trial will be to reproduce the positive data seen in NEXICART-1 in a larger patient population. Immix intends to submit a Biologics License Application to the FDA for ALA once 40 patients have been treated in NEXICART-2. Interim data for the trial is expected in mid-2025, with the final top-line results in ALA expected in mid-2026.

Beyond ALA, management has also communicated its plans to expand NXC-201 to additional autoimmune indications, which could maximize the commercial potential of the asset. An announcement on the details of these indications is anticipated in Q425, which we expect to be accompanied by initial clinical data to support the choice of targets.

In addition to NXC-201, Immix also holds legacy asset IMX-110 in its portfolio, development work on which is currently on hold as the company focuses on the CAR-T treatment. IMX-110 is a tissue-specific therapeutic and had been undergoing two Phase Ib/IIa trials in soft-tissue sarcomas (STS) and in r/r colorectal cancer in combination with BeiGene’s in-development anti-PD1 treatment tislelizumab. The company is in the process of collecting data from these trials, with the aim of seeking strategic options for the asset. We expect potential out-licensing partnership opportunities to be its key preference.

ALA: A rare disease with significant unmet need

ALA is a rare disease (33,000 estimated cases in the US, with an annual incidence of c 4,000 cases) caused by the abnormal build-up of amyloid proteins in tissues and organs. The condition is driven by the mutation of plasma cells in the bone marrow, which produce nonfunctional immunoglobulins that misfold to form amyloid light chains (either kappa or lambda). These light chains clump together to form amyloid fibrils that then get deposited in organs, ultimately resulting in progressive organ dysfunction.

ALA represents the most common type of systemic amyloidosis (accounting for c 70% of all cases), with a high mortality rate if untreated (over 45% within the first year of diagnosis). While ALA can affect almost all organs, the heart, kidneys and liver are the most affected. Notably, over 75% of ALA patients present with cardiomyopathy at the time of diagnosis, with the kidneys and liver involved in 50–60% of cases. ALA most commonly affects the elderly population (higher incidence in men) with a mean age of diagnosis of c 60 years and increasing incidence with age. Other than genetics and demographics, a key risk factor for ALA is the diagnosis of other plasma cell disorders such as MM (c 10% of patients diagnosed with ALA also have MM) and monoclonal gammopathy of undetermined significance.

Since ALA is a multi-system disease, initial symptoms are nonspecific (such as fatigue, weight loss, numbness and pain) and diagnosis therefore can be challenging. In addition to clinical examination and traditional blood tests (including cardiac biomarkers such as troponin/TnT and NT-proBNP), advanced testing such as tissue biopsy, Congo red staining, cardiac evaluation and specific diagnostics is required. This includes the serum free light chain (FLC) assay test, which measures the level of kappa and lambda light chains in the blood. A kappa/lambda ratio of less than 0.26 or greater than 1.65 is indicative of ALA.

Following diagnosis, patients are stratified based on organ involvement, disease severity and prognosis, using the Mayo staging systems. These models are primarily based on the level of cardiac involvement, which is the most important predictor of overall survival in ALA. The initial 2004 Mayo staging system stratified the disease into one of three stages according to TnT and NT-proBNP levels. In 2012, the staging system was updated to include difference in free light chains (dFLC), which is the difference between concentration of kappa and lambda light chains, as a third parameter. Under this system, patients are stratified into four stages. In 2015, a European group modified the Mayo 2004 model to better identify very high-risk patients, dividing stage III into two subgroups – IIIa and IIIb – according to a higher cutoff of NT-proBNP levels. Survival rates become progressively lower with higher Mayo staging, ranging from a median survival of 94.1 months for stage I to 5.8 months for stage IV patients following diagnosis. All three systems are currently being used interchangeably. The differences in the staging systems are detailed in Exhibit 2.

The treatment paradigm for ALA aims to reduce amyloid production by targeting the aberrant plasma cells, thereby improving organ function. The standard of care (SoC) induction treatment is a four-drug combination of subcutaneous daratumumab (Darzalex Faspro, Johnson & Johnson) with bortezomib, cyclophosphamide and dexamethasone (Dara-CyBorD). Daratumumab is a monoclonal antibody that targets CD38, an antigen expressed on plasma cells, and was approved as a combination treatment by the FDA in 2021, making it the first approved treatment for ALA. For patients achieving a very good partial response (VGPR) after two to four Dara-CyBorD cycles of 28 days each (VGPR = dFLC < 40mg/L), a total of six cycles are completed followed by single agent daratumumab as maintenance treatment for a total of two years, potentially followed by autologous stem-cell transplant (ASCT) as consolidation treatment. For patients not achieving VGPR, ASCT is suggested for eligible candidates. Note that only 20–25% of all patients diagnosed with ALA are eligible for ASCT given the multi-organ involvement and delayed diagnosis.

Despite frontline treatment, ALA remains uncurable and c 75% of patients are believed to be either refractory to frontline treatment (failure to achieve VGPR after two cycles and/or progressive disease while on therapy) or relapse following initial response. Despite ongoing clinical development efforts, there are currently no approved treatments for r/r ALA (as daratumumab is only approved as a frontline induction treatment). Immix is pursuing the strategy of a BCMA-targeted CAR-T therapy to address the condition, however, given the fragility of the patient population, side effects (eg neurotoxicity and CRS) remain an ongoing medical concern. In our view, the favourable safety profile of NXC-201 observed in the clinic to date represents a promising opportunity for Immix (Exhibit 3). We note that Immix has been awarded orphan drug designation (ODD) for NXC-201 as a potential treatment for ALA by both the FDA and the EMA.

Competitive landscape

As noted above, multi-level organ involvement (in particular the heart) poses incremental safety concerns on treatments under development for ALA, making it a highly challenging treatment area. We note that the competitive landscape is therefore not as crowded as other plasma-cell-based conditions, such as MM. The most advanced programs under clinical development are CAEL-101 (Caelum Biosciences/AstraZeneca) and Birtamimab (Prothena), both monoclonal antibodies in Phase III development. Interestingly, rather than targeting aberrant plasma cells, both candidates are amyloid-targeting treatments seeking to clear existing amyloid deposits on organs. We note that CAEL-101 and Birtamimab are focused on newly diagnosed, high-risk patients (Mayo stages IIIb and IV), categories that are not approved for frontline treatment with Dara-CyBorD.

In the r/r setting, there are currently no approved treatments, although certain drugs are used off-label with varying efficacy. These includes plasma cell directed therapies such as daratumumab and AbbVie’s venetoclax (targeting a subset of patients with the t(11;14) translocation). They have shown efficacy in early-stage clinical development, although it is unclear if they are being actively developed for r/r ALA. In addition, approved r/r MM treatments are often used off-label in the treatment of r/r ALA. These include immunomodulatory drugs such as lenalidomide and pomalidomide in combination with the corticosteroid dexamethasone. However, these have been associated with thrombotic complications and increased levels of NT-proBNP. In addition, the proteasome inhibitor ixazomib (Ninlaro) was studied in combination with dexamethasone in a Phase III study (TOURMALINE-AL1) by Takeda, although it was subsequently terminated as it failed to meet the primary endpoint of improved overall hematologic response compared to SoC, despite encouraging CR and progression free survival.

BCMA-targeting immunotherapies (including bispecific antibodies, antibody-drug conjugates (ADC) and CAR-Ts) have seen significant success in MM and are widely considered to be promising treatments in ALA despite the lower levels of BCMA expression as compared with MM. In addition to Immix’s NXC-201, which is undergoing Phase Ib/II development, other BCMA-targeting therapies in development for ALA include the ADC belantamab mafodotin (currently in Phase I/IIa development).

Latest news: Encouraging progress for NEXICART-2

NEXICART-2 background

NEXICART-2 is a US-based open-label, single-arm, multi-site dose escalation/expansion Phase Ib/II trial, designed to assess the safety and efficacy of NXC-201 as a potential treatment for r/r ALA. We note that the efficacy measure is based on hematological response according to consensus recommendations in ALA. The study aims to recruit 40 r/r ALA patients, the majority of whom are intended to be enrolled in the Phase II portion. Eligibility criteria for NEXICART-2 include:

• patients must have adequate cardiac function (patients with Mayo stage IIIb ALA or New York Heart Association (NYHA) stage 3 or 4 heart failure are excluded);
• patients must not have been treated with prior BCMA-targeting therapies; and
• patients must not have concomitant MM, which is the case of c 10% of ALA patients.

We note that the study design for NEXICART-2 differs from the NEXICART-1 trial, which did allow patients with pre-existing severe cardiac involvement, prior BCMA-targeted therapy exposure and with concomitant MM. Moreover, NEXICART-1 tested three separate doses (150m CAR-T cells, 450m CAR-T cells and 800m CAR-T cells, all of which delivered CRs), whereas NEXICART-2 plans to study only the first two doses, with 450m selected as the optimal dose for the Phase II expansion phase. We believe the design for NEXICART-2 has been modified to maximize the trial’s probability of efficacy and success.

Patient dosing for NEXICART-2 commenced in July 2024, and the trial advanced to the dose expansion stage in October 2024. Six patients have been dosed on the trial to date (three each across the two dose cohorts). To our knowledge, this is the only active clinical trial in the US evaluating a CAR-T therapy for the treatment of ALA. Given that alternative treatment options for this fragile patient population are limited, we believe there is a sizeable opportunity for Immix in this space.

Interim update

In December 2024, Immix presented an encouraging interim update on the progress of NEXICART-2, corresponding to the first four patients from the trial. Three of the patients were dosed at 150m CAR-T cells, while the fourth received a 450m cell dose. The four patients had a median of four prior lines of therapy (range: 2–6), and two of the patients had received a prior ASCT. As part of the trial protocol, disease markers were measured at enrolment; dFLC was used for three of the patients while M-spike was used for one who did not have elevated dFLC at enrolment.

Per the data cutoff of 14 November, the median follow-up was 85 days (range: 29–141), and at this stage, all four patients showed normalized disease markers within 30 days of receiving NXC-201. Furthermore, two of four patients showed a CR, and the remaining two patients were classified as measurable residual disease (MRD) negative (10^-6)^[1], with management estimating that they could be confirmed as CR within the coming weeks or months. For the disease marker measures, the latest update showed significant reductions to < 1mg/dL for the three patients based on dFLC measures, while the patient measured by M-spike concentration showed full resolution (Exhibit 4).

In addition to these encouraging results, it was noted one of the patients improved their NYHA class from class II to class I. This occurred within 14 days of being treated with NXC-201 (Exhibit 5).

NXC-201 was also found to be generally safe and well tolerated given the nature of the treatment as a CAR-T therapy, consistent with the safety observations from the NEXICART-1 trial. There were no reported cases of immune effector cell-associated neurotoxicity syndrome (ICANS), a positive sign with potential to address some of the key limitations of current FDA-approved CAR-Ts (discussed in further detail below). In terms of CRS, while two patients (both on the 150m dose) showed no CRS, only low-grade CRS was observed in the other two patients (one of which was grade 1 and the other grade 2) and both of these saw onset at day three and had a duration of less than 24 hours, which is considered manageable in this field. Hematologic adverse events included neutropenia (low neutrophil count) in the four patients (three of which were grade 3, one of which was grade 4), which is another common side effect of CAR-T therapy. Importantly, there have been no cases of febrile neutropenia, treatment-related infections, cardiac toxicity and no patient deaths. In January 2025, the company announced that the Phase Ib six-patient safety-run has been completed (three patients each in the 150m and 450m CAR-T cells cohorts), with the trial moving on to the Phase II expansion where 34 patients will be administered the 450m dose. The safety-run had restrictions on patient enrolment (one patient every 28 days) and we now expect enrolment to accelerate.

Collectively, we believe this interim update represents a positive start to the NEXICART-2 trial, however we acknowledge that it corresponds to a small patient population. The next readout for the trial is anticipated in mid-2025 and could represent a notable catalyst for investor attention should the encouraging trend continue as more patients are dosed. We note that final top-line clinical data are expected in mid-2026, after which management has communicated that it intends to submit the regulatory package to the FDA for accelerated approval within the same year.

ASH update: Sustained positive NEXICART-1 data

The Israel-based NEXICART-1 trial is a Phase Ib/II open label study designed to assess the safety and efficacy of NXC-201 in r/r ALA. As discussed above, while the current focus for Immix is on the US-based NEXICART-2 trial, the company presented an encouraging update from NEXICART-1 at the 66th annual American Society of Hematology (ASH) meeting in December 2024.

The data update corresponded to 16 r/r ALA patients who were treated with NXC-201 as part of the trial. We note that patients were infused with CAR-T cells at doses of 150m cells (n=1), 450m cells (n=2), as well as 800m cells (n=13; as noted above, this dose is not being assessed in NEXICART-2). The patients were r/r to a median of four prior lines of therapy (range: 3–10). The results, which were also published in the Journal of Clinical Oncology, are as follows:

• Overall response rate (ORR) was 94% (15/16 patients).
• CR rate was 75% (12/16 patients).
  • 9/16 patients were MRD negative (10-5).
• Organ response rate was 62% (8/13 evaluable patients).
• The best duration of response was reported as 31.5 months as of 9 December 2024, and it was noted that the response is ongoing.
• Zero cases of neurotoxicity.
• Zero cases of high-grade CRS (greater than grade 3).
  • Median CRS duration was two days (range: 1–4 days).
  • 2/16 patients experienced no CRS.
  • 3/16 patients experienced grade 1 CRS.
  • 8/16 patients experienced grade 2 CRS.
  • 3/16 patients experienced grade 3 CRS.

We believe these results further support the potential of NXC-201 to deliver a practical CAR-T option for r/r ALA, especially since the patient population of this trial was particularly fragile (13/16 had cardiac involvement including 6/16 with NYHA stage 3 or 4 heart failure; patients who had been exposed to prior BCMA-targeted therapy and with concomitant MM were eligible for this trial). While NEXICART-2 remains the strategic priority, management has indicated it will continually follow-up on the 16 patients on the NEXICART-1 to assess long-term data, which should support regulatory discussions.

CAR-Ts: Current challenges and opportunities

CAR-T therapies 101

CAR-T therapies utilize the natural function of T cells (white blood cells that play a crucial role in our bodies’ immune systems) to target specific antigens. T cells detect foreign materials and recognize aberrant proteins/antigens expressed on the surface of cells and trigger immune responses to destroy the targeted cell. CAR-T therapies work by modifying (genetically engineering) the T cells of a patient to specifically recognize these cells as foreign material, initiating targeted destruction.

CAR-Ts have to date been applied to the treatment of hematological/blood cancers by targeting the CD19 and BCMA antigens. Scientific data and studies support the rationale of targeting BCMA in ALA, given that the antigen is highly expressed on amyloidogenic plasma cells, which are implicated in ALA. Targeting these aberrant plasma cells using anti-BCMA treatments, including CAR-Ts, has therefore been increasingly seen as a promising option for this indication. One of the possible limitations of using traditional CAR-Ts in ALA is believed to be toxicity (given common CAR-T side effects such as ICANS and CRS), which can be a challenge given the fragile patient population with impaired organ function. However, as previously discussed, NXC-201’s favorable safety and tolerability profile to date supports its continued development as a potential treatment for r/r ALA.

Six CAR-T therapies are currently approved, all in hematological cancers. Kymriah (Novartis) was the first CAR-T therapy approved in the US (in August 2017), specifically for the treatment of r/r B-cell acute lymphoblastic leukemia in children and young adults. There are currently six FDA-approved CAR-Ts, with the latest two being Abecma (Bristol Myers Squibb/Celgene) and Carvykti (Johnson & Johnson), both of which are BCMA-targeting treatments for MM (Exhibit 6). Collectively, these CAR-Ts generated c $3.7bn in sales in 2023, indicative of the commercial potential of these treatments.

Side effects represent a key challenge with current options

There are several advantages of CAR-T cell therapies such as a targeted mechanism of action and the ability to generate a durable response after a single administration, which may improve patient compliance. However, the current approved CAR-Ts are somewhat limited by high costs, manufacturing complexities and a lack of ‘off-the-shelf’ options. Another key challenge with CAR-T treatments is safety given the treatment is associated with high-grade CRS, an acute inflammatory syndrome characterized by fever and organ dysfunction, as well as neurotoxicity (marked by severe confusion, seizure-like activity and impaired speech). Given these hindrances, CAR-Ts have limited accessibility worldwide, including in the US, with Immix’s management estimating that only c 5% of US hospitals are capable of administering CAR-Ts, and CAR-T therapies are often limited to large hospitals in metropolitan regions. As such, we believe there is a necessity to increase the number of centers that can administer these treatments, since patients currently need to travel long journeys to access this type of treatment and, given the potential safety concerns, must also stay for extended periods at or near these centers for monitoring.

NXC-201 may offer differentiation with favorable safety profile

As discussed above, while CAR-Ts can offer effective treatment for certain hard-to-treat conditions, currently approved CAR-Ts are not considered outpatient options, due to the risk of side effects such as CRS and neurotoxicity. Immix attests that NXC-201 may offer a solution to the challenges associated with current CAR-Ts, given the desirable safety data NXC-201 has generated in the clinic to date. A comparison of selected clinical data from the NEXICART-1 trial (n=58, including 50 MM patients and eight ALA patients) highlighted the short CRS duration for NXC-201 versus approved and in-development CAR-T treatments (Exhibit 7).

Based on the favorable safety profile, reduced risk of neurotoxicity (zero neurotoxicity reported in ALA patients to date) and manageable CRS, Immix is positioning NXC-201 as potentially the first outpatient CAR-T treatment, whereby patients would not necessarily require hospitalization or need to stay in close vicinity for long periods to the administering medical centers for monitoring, as is the case with currently approved CAR-Ts. This could make it easier for the treatment to be offered in smaller and/or more diverse healthcare facilities and increase access to care.

CAR-Ts in the headlines: Benefits vs risks

CAR-Ts garnered attention in news headlines throughout 2024 due to the FDA’s investigation into the drug class for risks of T cell malignancies in patients who have received BCMA- or CD19-directed autologous CAR-T therapies. As a result of the investigation, the FDA required these products to have black box warnings. However, despite this class-wide warning, the FDA continued to communicate the overall benefits of these approved treatments, and an FDA advisory committee even voted in favor of moving Carvykti and Abecma to earlier-line treatment settings for MM, after the black box warnings were required. Furthermore, as highlighted at the company’s key opinion leader event in December 2023, we understand that these warnings are not a deterrent to clinicians who consider the use of CAR-Ts, given that the benefits often outweigh the risks for hard-to-treat conditions and secondary malignances are not uncommon in other drug classes used to treat such conditions, such as chemotherapy.

Importantly, Immix has assured the market that it has not seen such malignancies in the clinical data to date for NXC-201. Moreover, research from a Stanford Medicine study has characterized the risk of these secondary malignances as low.

Sensitivities

Immix is subject to the typical risks associated with drug discovery and development, with some additions due to its focus on CAR-Ts. As a pureplay biotech, Immix will be affected by delays or failures in its clinical trials, regulatory discussions and outcomes, the successes of competitors in the space, potential partnering setbacks, as well as risks associated with financing and the commercialization of its drug candidates. Following the strategic realignment of its business priorities in 2024, which saw the company deprioritize MM as a target indication for NXC-201 as well as halt additional clinical activities on legacy asset IMX-110, Immix’s risks are somewhat concentrated on its lead asset, NXC-201, in r/r ALA. Therefore, the prospects of the company rely on this single development program in order to drive future value. This exposes the company’s outlook to binary events (success or failure of the clinical trial), with data readouts being of utmost importance. We expect management’s decision to pursue other autoimmune indications (from late 2025) to mitigate some of this risk in the medium to long term.

Another key sensitivity is the challenges related to the CAR-T class. CAR-T manufacturing is a complex (there can be significant variability in samples between patients, requiring specific customization) and time-consuming process. It entails significant outlay, oversight and technical know-how. According to various reports, manufacturing costs for CAR-Ts can range from $20k to upwards of $100k per patient. In this context, it will be crucial for Immix to secure a manufacturing agreement with a contract development and manufacturing organization at favorable terms as the asset advances through the clinic towards commercialization.

Regulatory issues are another sensitivity to consider, especially for this drug class. Following recent headlines of risks of secondary malignancies, the FDA now requires black box warnings for all current approved CAR-Ts. However, we note that despite the class-wide warning, the regulators also communicated the overall benefits that these therapies present for the challenging indications that they target. Further research has since characterized the risk of these secondary malignances as low and Immix has communicated that no such issues have been observed in the clinical data to date for NXC-201. In terms of its track record in the clinic, data from the NEXICART-1 trial in ALA were encouraging. Immix will need to demonstrate that similar results can be obtained in the NEXICART-2 trial to satisfy the US regulators. The next program update on enrolment is expected in Q124 with interim readouts in mid-2025.

Access to financing is another overriding risk for clinical-stage biotechs given the significant upfront investment required and long lead times to reach the market. Immix has been funding its development efforts through external equity funding, with current capital at hand sufficient to fund operations into Q425. With top-line data only expected in mid-2026, management would need to raise further funds in late 2025 to support trial completion. In accordance with this sensitivity, a related risk is the potential of dilution for current shareholders, should the required funds be raised through an equity issuance.

Valuation

We refresh our valuation for Immix following a strategically important year that saw the company redefine its business priorities to focus exclusively on r/r ALA as the lead target indication, putting on hold its development efforts in MM. We see merit in this strategy, given that ALA is a less explored and less competitive space than MM, which has over 15 approved treatments (versus one in ALA). We note that MM already has five approved BCMA-targeted treatments, including two CAR-Ts (Abecma and Carvykti), two bispecific antibodies (Tecvayli and Elrexfio) and one antibody-drug conjugate (Blenrep), with the CAR-Ts now approved as second-line treatment. Despite demonstrating superior safety signals in clinical trials, we believe this competition would have made it more challenging for NXC-201 to gain sufficient foothold in the market. During this period, the company also decided to halt further clinical activities on legacy asset IMX-110 and as indicated previously, is in the process of collecting data from these trials with the aim to explore strategic options, including potential out-licensing partnership opportunities.

Following the recent clinical progress made by Immix and increased visibility on the NEXICART-2 trial timelines, we have revised our underlying assumptions and estimates for Immix’s development programs. For NXC-201 in r/r ALA, we have updated our estimate for peak sales to c $520m (versus c $350m previously) with PoS raised to 30% (from 25% previously), given the continuing progress through the NEXICART-2 study to date, including the initial encouraging data on the first four treated patients. We continue to attribute a market launch in 2028, with peak sales achieved in 2034. Key market assumptions are detailed in Exhibit 8. This translates to a rNPV/share of $3.2 (versus $1.4 previously). We note that NXC-201 has been granted an ODD in ALA by both the FDA and EMA, which should provide seven and 10 years of market exclusivity in the US and Europe, respectively, providing it is successful with regulatory approval. As part of the in-licensing agreement for NXC-201, Immix will be required to pay a 5% royalty rate on sales to the licensors, Hadasit Medical Research Services & Development and BIRAD Research and Development Company. It is also required to make a milestone payment of $20m once sales exceed $700m.

While Immix has communicated that it is open to all commercialization strategies (including development and distribution partnership, full out-licensing and self-commercialization), for our model we assume that Immix will sign an out-licensing deal for NXC-201 in 2027, after completion of the Phase Ib/II NEXICART-2 study in H226. We assume that Immix will secure a licensing deal worth up to $500m, including an upfront payment of $50m and additional clinical, regulatory and commercial milestone payments of $450m. We also assume a flat 15% royalty rate on sales. We base this on previous Phase I/II deals in MM, given limited such deals in ALA. For reference, we note that AstraZeneca subsidiary Alexion fully acquired Caelum Biosciences in September 2021 for $500m, including an upfront option exercise price of $150m with additional $350m in regulatory and commercial milestones. This was based on Phase II data for its monoclonal antibody CAEL-101 in ALA. Alexion had previously acquired a minority stake in Caelum Biosciences in January 2019 for $60m.

We believe that Immix may be able to secure competitive licensing terms due to NXC-201’s differentiated safety profile, the lack of available treatment options in ALA, as well as the therapy’s potential application as an outpatient treatment, which, if demonstrated, may increase the scalability of treatment adoption.

While we had previously also ascribed value to NXC-201 in MM, given that Immix is no longer pursuing this indication, we have removed it from our valuation. For IMX-110, we understand that development work is currently deprioritized and therefore we update our assumptions for the asset across the two programs. We now model no ongoing internal R&D on IMX-110, assuming the asset to be out-licensed in 2026 for a total deal value of up to $200m, including an upfront payment of $20m and up to $180m in development, regulatory and sales milestones. We also assume a flat 15% royalty rate. We assume the partner to take over Phase II development work across the two programs, with commercial launch and peak sales now expected in 2031 and 2036, respectively (previously 2029 and 2034). We have also reduced the PoS for the two programs to 7.5% (vs 15% for STS and 10% for solid tumors previously). This results in an rNPV/share of $0.3 (previously $0.7) for STS and $0.4 for solid tumors (previously $0.5).

Reflecting the aforementioned changes and accounting for the latest end-Q324 net cash position ($19.7m), our valuation for Immix adjusts to $125.8m or $4.6/share (from $123.1m or $4.5m/share previously). Note that this does not include the potential contribution from the additional autoimmune indications that the company plans to explore for NXC-201 from 2025.

Exhibit 9 presents a breakdown of our rNPV valuation for Immix.

Financials

Immix’s Q324 results were reflective of a period with heightened clinical activity, following the initiation of the US-based NEXICART-2 trial in July 2024. The company recorded $4.4m in R&D expenses during the quarter, its highest since listing and approximately double the figure in Q323 ($2.1m) and Q234 ($2.2m). This was related to increased clinical activity and new site onboarding costs (new sites opened in August 2024 in Cleveland Clinic, UC Davis, and Sutter Health, in addition to the lead site at Memorial Sloan Kettering Cancer Center). With the pace of recruitment expected to pick up after following the initial six-patient safety-run (only one patient a month was allowed to be recruited during this phase), we expect R&D expenses to rise in Q424 and FY25. The Q324 G&A expenses were reported at $2.9m, up c 19% over the last quarter’s figure of $2.5m. This increase was related to higher fees for investor relations ($543.4k) and employee compensation related to new hiring ($355.7k), which was partially offset by decreased legal fees related to subsidiary Nexcella ($309.6k) and lower stock-based compensation ($69.1k). Overall, Immix reported an operating loss of $7.4m in Q324, up 63.5% y-o-y ($4.5m in Q323) and 57.3% higher than the Q224 figure of $4.7m. Free cash outflow for the quarter was $4.3m, with the impact of the operating performance partially offset by a favorable working capital position (increased accounts payables and accrued expenses).

Based on the Q324 performance and near-term visibility of Immix’s development plans, we have made adjustments to our FY24 and FY25 estimates. While the company is pre-revenue, we remind readers that Immix was awarded an $8m grant from CIRM in July 2024. As part of the Q324 release, management communicated that it expected to receive funds under the grant beginning in November 2024 (previously September 2024). We had previously assumed that $2m of the grant income would be received in 2024 with the remaining $6m in 2025, which we have now adjusted to $1m and $7m in Q424 and FY25, respectively. We have also raised our R&D estimate for FY24 to $15m (from $13.4m previously) to reflect the 9M24 run rate. For FY25, we have increased our R&D estimate to $18m (from $15m previously) to reflect the accelerated pace of recruitment expected in 2025. We have also increased our estimate for G&A expenses to $9.6m in FY24 and $10.1m in FY25 (from $8.5m and $9.4m previously). Overall, our revised operating loss estimates for FY24 and FY25 are $23.6m and $21.1m, respectively (previously $20.0m and $20.2m).

Immix ended Q324 with a net cash balance of $19.7m, and we expect this to be supported by the receipt of the $8m grant income from CIRM. Based on our projected cash burn rates, we continue to estimate the company being funded into Q425, in line with management guidance. We forecast that the company will need to raise $5m in H225, and another $25m in 2026, before signing a partnership deal in 2027. As an added sensitivity, should a licensing deal not materialize, we estimate that the company would be required to raise another $15m in 2027, before turning cash flow positive in FY28 following the potential launch of NXC-201 in ALA. Our model reflects these capital raises as illustrative debt. Should the funds (a total of $45m across FY25–27) be raised through an equity issuance, Immix would need to issue 19.1m shares, which (at the last closing price of $2.3) would decrease our per-share valuation to $3.6/share, from $4.6/share currently. The number of shares outstanding would increase to 47.1m, from 27.5m currently.