Adicet Bio, Inc. Common Stock Study update

Go ahead. Good morning, everyone, and thank you for joining us today.

This morning, we announced positive data for prula-cel, and we now look forward to discussing the results. Joining me today is Dr. Lloyd Klickstein, our interim Chief Medical Officer and a member of our board of directors, who will summarize the clinical data to date, supporting our decision to advance prula-cel into a pivotal study. After that, we'll be joined by Dr. Blake Aftab, our Chief Scientific Officer, to discuss the supporting evidence of immune reset observed in our clinical study. Then we'll open it up for Q&A, where we'll be joined by Nick Harvey, our Chief Financial Officer. Please note that today's call may include forward-looking statements based on our current expectations. These statements represent our judgment as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from results discussed.

Please refer to our filing with the Securities and Exchange Commission for more information. Today is a very exciting day for Adicet and, more importantly, for patients as we share promising data that demonstrated compelling safety and efficacy results for prula-cel in patients with systemic lupus erythematosus, or SLE, with or without lupus nephritis. In heavily pre-treated patient population, at the 12-month mark, 50% of evaluable lupus nephritis patients achieved complete renal response, and 54% of the overall lupus population achieved DORIS remission. Importantly, these remissions were achieved with a generally highly favorable safety profile, with no IEC-HS, no ICANS, and no CRS above grade 2. We understand the biology underlying prula-cel's favorable safety profile and its differentiation from the safety profile of alpha beta CAR T therapies, as you will see in the slides ahead.

All patients discontinued immunosuppressants, and all but one patient tapered back on steroids to 5 milligrams or less of prednisone equivalent. We also saw evidence of immune reset with complete CD19 positive B-cell depletion, followed by emergence of naive B-cell repertoire. What excites us the most is the opportunity to potentially redefine the standard of care for lupus patients. From a lifetime of chronic immunosuppressants and steroid treatment, which have modest efficacy, cumulative toxicities, and a negative impact on their quality of life, to a potential one-time therapy that achieves high rates of immunosuppressant-free clinical remissions. These data position us exceptionally well with a path for potential approval and a large commercial opportunity ahead. We've aligned with the FDA on a single-arm pivotal study in lupus nephritis, and we plan to initiate startup activities for the study this coming quarter.

Given the high rate of DORIS remission observed in the study and consistent with regulatory precedent, we expect to expand the single-arm pivotal study to include lupus patients without nephritis. So stay tuned on that. Our team has established an excellent track record in enrolling lupus patients, and we saw strong interest from both patients and investigators to participate in the clinical study. We believe this positions us well for rapid enrollment of the pivotal study. Given the generally favorable safety profile observed with prula-cel, we aligned with the FDA to enable outpatient dosing of prula-cel. The off-the-shelf availability and scalable manufacturing of prula-cel provides commercial advantages to address the unmet medical need of many patients living with lupus.

Turning to the commercial opportunity, there are approximately 35,000 refractory lupus nephritis patients with organ or life-threatening disease despite currently available therapies, and another 35,000 refractory non-renal lupus patients with organ or life-threatening disease who may benefit from a potential therapy like prula-cel. We delivered on every key objective we wished for in this study. Rapid enrollment, a favorable safety profile supporting outpatient dosing, and high rates of immunosuppressant-free CRR and DORIS remission. prula-cel is uniquely suited to potentially make a meaningful difference for lupus patients while generating value for shareholders. The strength of the data we'll show you today further reinforces our confidence in the prula-cel program and opportunities ahead. We anticipate a number of meaningful milestones as we continue to advance the program. I'll now pass it over to Lloyd to walk you through the clinical data in more details on the next slide.

Lloyd? Thanks, Chen. Here's a quick review of the trial design.

This is a basket study which includes several autoimmune indications, as you can see on the left, with a dose expansion element, as you can see on the right. We're discussing the lupus cohort with or without nephritis today. The study periods include informed consent, a screening period, the conditioning regimen, a single dose of prula-cel, a 28-day DLT evaluation period, and then patient follow-up. The primary endpoint was safety and tolerability. Secondary and exploratory endpoints focused on biomarkers of drug activity, including B-cell depletion and reconstitution and immune reset, while the clinical efficacy endpoints were focused on complete responses and remission. We started enrolling lupus nephritis patients first and subsequently expanded the cohort to enroll lupus patients without nephritis. Let's next look at patient baseline characteristics.

This is a summary of the baseline characteristics of the 16 lupus nephritis and 8 lupus patients without nephritis who were enrolled in the study. You can see the study participants are typical for lupus patients, primarily women with a mean age of 35 who have been living with the disease for years. These patients had inadequate responses to prior treatment, all had received at least three prior therapies, and 71% had received four or more prior immunosuppressants in addition to glucocorticoids. Their mean baseline SLEDAI score was 13, and those patients with nephritis had a baseline mean urinary protein creatinine ratio, or UPCR, of 2.8. These patient baseline characteristics are similar to other datasets from company-sponsored clinical studies with B-cell depleting autologous cell therapies.

This is a summary slide of the CRR rate in the lupus nephritis patients and the DORIS rate in the entire cohort of lupus patients with and without nephritis. As you can see, the CRR rate reached 50% at month 12, and the DORIS rate reached 54% at month 12. Importantly, these remission rates occurred while patients were immunosuppressant-free, and their glucocorticoid dose was 5 milligrams or less of prednisone equivalent. All 12-month CRR and DORIS remissions are ongoing with a follow-up of 12 to 21 months, except one patient with a UPCR of 0.65 grams per gram after month 12, but who continues to remain off immunosuppressants. Focusing on the five patients with the CRR at month 12, two of them were already a CRR at month six.

At month nine, they remained in CRR, and an additional two patients reached CRR, and by month 12, one more patient reached CRR. A similar pattern was observed for the DORIS remissions. Those patients who haven't yet reached month 12 are on a clinical trajectory that we expect will be generally consistent with the efficacy we're reporting today. Notably, in addition to the 50% CRR at month 12, an additional 20% of the nephritis patients had at least a 50% decrease in proteinuria from their baseline levels, which is defined as partial renal response per protocol. As a rheumatologist, the most compelling aspect of these results to me is the potential to change the standard of care for people with lupus. Currently, these patients are faced with a lifetime of chronic immunosuppressants and steroid treatment, which have modest efficacy, cumulative toxicity, and an adverse effect on their quality of life.

A one-time therapy that achieves high rates of immunosuppressant-free clinical remissions would be transformative. Let's talk about the safety profile. Next slide, please. prula-cel was generally well-tolerated and showed a favorable safety profile appropriate for outpatient dosing. Across the 24 safety evaluable patients, there were no dose-limiting toxicities, no Immune Effector Cell HLH-like Syndrome, or IEC-HS, no ICANS, and no CRS events greater than grade 2. We have so far enrolled 48 autoimmune disease patients, and this generally favorable safety profile is consistent throughout the entire autoimmune disease program. In this study, grade 1 or 2 CRS occurred in just 25% of patients. Of infections that occurred, most were grade 1 or 2, with grade 3 in just two of the 24 patients. There were no cases of GVHD.

We shared our safety data with the FDA and aligned to make prula-cel available going forward for enrollment in the outpatient settings. When compared to safety data reported for alpha/beta CAR T therapies in autoimmune diseases, we believe prula-cel is generally better tolerated. This favorable safety profile with no IEC-HS, no ICANS at all, and no CRS events greater than grade 2 is consistent with the biology of gamma/delta CAR T cells, which is different from that of alpha/beta CAR T. Let's now discuss the scientific foundation underlying these findings and why we believe prula-cel's differentiated biology may contribute to its generally favorable safety profile to date. To better understand the promising results, it is important to look at how gamma delta T cells differ from alpha beta CAR T cells.