Full Press Release Details
for Dialysis Prevention REACT [REnal Autologous Cell Therapy]
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Agenda Opening Remarks 01 REACT Phase 2 RMCL-002 Data 02 Plans for Phase
3 Program (Studies REGEN-006 and REGEN-016) 03 04 Advancing a Comprehensive Clinical Plan 3
Disrupting the CKD Treatment Landscape Renal Autologous Cell Therapy:
REACT (rilparencel) proprietary autologous cellular therapy being evaluated to preserve kidney function in diabetic patients at high risk of kidney failure 4
What is REACT and Why is it Relevant? Our Product Unmet Needs Our
Goals Our Plan Over 35 million U.S. adults Preserve kidney function REACT is a proprietary Phase 3 clinical program have chronic kidney cell therapy using the proact 1 and proact 2 are Reduce or potentially 1 disease (CKD) patient's own
kidney cells underway in patients with eliminate time spent on Stage 3b / 4 diabetic kidney More than 135,000 of dialysis Early clinical data disease these CKD patients demonstrate a potential to Return autonomy to progress to dialysis every
preserve kidney function Potential label expansion to patients and their families 2 year re-dose REACT for long- May provide greater benefit term dialysis prevention Total annual costs to to higher-risk CKD patients Medicare for patients with CKD
(including ESRD) 1 exceed $138B 1. CDC Fact Sheet. https://www.cdc.gov/kidneydisease/publications-resources/ckd-national-facts.html 2. USRDS 2023 Annual Report 5
REACT Goal: Preservation of Kidney Function ProKidney's
REACT Autologous Cell Therapy 6
Overview of the REACT Clinical Program Lead Platform Programs*
PRECLINICAL IND PHASE 1 PHASE 2 PHASE 3 STATUS Pivotal Trial Program Diabetes Type II - Prevent/Delay CKD 3/4 006/proact 1 Ongoing 2 (20-50 ml/min/1.73m , N = 600) Diabetes Type II - Prevent/Delay CKD 3/4 stratified for SGLT2i Enrollment
016/proact 2 2 (20-44 ml/min/1.73m , N = 600) Mid-2024 Enrollment Long term follow-up study for patients previously treated with REACT 008 4Q 2023 Supportive Trials Diabetes Type II - Delay CKD 4/5 Trial 003 2 (14-20 ml/min/1.73m , N = 10)
Completed Diabetes Type II - Prevent/Delay CKD 3/4 Fully 002 2 (20-50 ml/min/1.73m , N = 81) Enrolled Diabetes Repeat Dose Prevent/Delay CKD 3/4 Fully 007 2 (20-50 ml/min/1.73m , N= 50) Enrolled Fully Multi / extended-dosing for previously
REACT-treated patients 015 Enrolled Trial Congenital Anomalies - Prevent/Delay 004 2 Completed (14-50 ml/min/1.73m , N= 5) Frozen bilateral Unilateral *As of October 2023 product injections injections 7
Unmet Clinical and Payer Need in High-Risk CKD Patients REACT May
Delay Need for Dialysis in Highest-Risk Progressors CKD is defined as abnormalities of kidney structure or function, present for > 3 months CKD is classified based on Cause, GFR category (G1-G5), and Albuminuria (A1- A3),
abbreviated as CGA Standard of Care o Antihypertensives o ACEi Risk for ESRD o ARB o Glucose & Inflammation Low Reduction o SGLT2i Moderately o DPP-4 Moderately Increased Increased o GLP-1 REACT's Hig High h Target Population V Ver ery y
Hig High h Today, clinical priorities for patients with Stage 4 CKD (G4) are largely focused on treating co-morbidities and preparing patients for transplantation or dialysis Janet B McGill et al. BMJ Open Diab Res Care 2022; 10:e002806 8
Therapeutic Options to Delay the Need for Dialysis in Patients with
Stage 4 Chronic Kidney Disease are Limited Study Active Product Subjects with Stage 4 CKD (%) 1 Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy Canagliflozin (SGLT2 inhibitor) 0% 2 Dapaglifozin in Patients with CKD Dapaglifozin
(SGLT2 inhibitor) 14% 3 Empaglifozin in Patients with CKD Empaglifozin (SGLT2 inhibitor) 34% 4 Effect of Finerenone on CKD Outcomes in Type 2 Diabetes Finerenone (Selective MRA) < 10% Rationale, Design, and Baseline Data of FLOW - a Kidney
Outcomes Trial with Once Semaglutide (GLP-1RA) 10% 5 Weekly Semaglutide in People with Type 2 Diabetes and CKD All recent landmark clinical trials in CKD focus on Stage 2/3 CKD 1. Perkovic V et al. N Eng J Med 2019 4. Bakris G et al. N Engl J Med
2020 2. Heerspink H et al. N Engl J Med 2020 5. Rossing P et al. Nephrol Dial Transplant 2023 9 3. Herrington et al. N Engl J Med 2023
While New Therapies Are a Step Forward, Patients Still Lose Kidney
Function and Experience Clinically Significant Events Standard of Care has Limitations Current SGLT2 Inhibitors are Blockbusters 1 Patients continue to lose kidney function on SGLT2 inhibitors Current standard of care does not prevent events in ~
50- 2 and progress to Stage 4/5 CKD 75% of people with diabetic kidney disease 2 DAPA: -2.86 ml/min/1.73 m per year versus 2 SoC: -3.79 ml/min/1.73 m per year Dapagliflozin: 19 patients required treatment to prevent one primary While dapagliflozin
demonstrated <1.0 ml/min/yr difference in eGFR, it was able to achieve a reduction in clinically important events outcome event 1. Standard of care includes ACE inhibitors, angiotensin receptor blockers and SGLT2 inhibitors 10 2. Heerspink HJL et
al. N Eng J Med 2020 Cumulative Incidence (%) of 50% decrease in eGFR, kidney failure and death Change in Estimated GFR (ml/min/1.73 m2)
RMCL-002 Interim Analysis August 2023 Data Cut 11
In this Phase 2 Study, REACT Demonstrates the Potential for
Preservation of Kidney Function in Patients with Diabetes and Advanced Kidney Disease REACT showed potential to preserve kidney function for up to 30 months in Key Findings several patient groups REACT's benefit on kidney
function was most notable in patients who had the 1 highest risk of kidney failure (CKD 4 with high UACR ) REACT injections were well tolerated with a consistent safety profile comparable to kidney biopsy We are enriching our Phase 3
Proact 1 Study to include more patients with Next Steps the highest risk of kidney failure 12 1. UACR = urine albumin-to-creatinine ratio (a measure of albuminuria)
RMCL-002: Trial Design Active n = 41* st nd 1 2 EOS REACT
REACT Month 24 follow-up nd Injection Injection after 2 injection = 6 months uu uuuuuu Screening R st nd 1 2 EOS Visit and u = follow-up visit 1:1 nd REACT REACT Biopsy Month 12 follow-up after 2 injection nd Injection Injection
after 2 injection Day -60 to Day 0 uuuu Deferred n= 42 Key Entry Criteria Study Endpoints Study Timeframe Type 2 Diabetes Mellitus (DKD) REACT and Procedure Related RMAT granted for Phase 3 program in January Adverse
Events 2022 Male or female 30-80 years of age Change in kidney function 13 subjects remaining on study (n= 9 in Deferred 2 eGFR 20 and 50 mL/min/1.73m (assessed by eGFR) arm) and will complete by YE 2023
Not on kidney dialysis, HbA1c <10% 13 RMAT = Regenerative Therapy Advanced Medicine
Study Objectives and Endpoints To assess the safety and
efficacy of up to two REACT injections given 6 Study Objectives months apart and delivered into the biopsied kidney using a percutaneous approach Procedural- and investigational product-related adverse events Study Endpoints Change
in kidney function as measured by serial measurements of estimated glomerular filtration rate (eGFR) 14
Study Demographics are Balanced and Represent a High-Risk CKD
Population ACTIVE DEFERRED (n=41) (n=42) Age, years (mean +/- SD) 66.1 +/- 9.9 64.6 +/- 8.9 Female : Male, % 29% : 71% 36% : 64% Hispanic or Latino, % 17% 10% Race, % Black or African American 2% 14% White 93% 71% Other 5% 14% Blood pressure, mm HG
133 / 72 135 / 73 2 eGFR, ml/min/1.73m (mean +/- SD) 33.9 +/- 8.6 31.8 +/- 7.4 Stage 3A CKD, n (%) 4 (10%) 3 (7%) Stage 3B CKD, n (%) 21 (51%) 19 (45%) Stage 4 CKD, n (%) 16 (39%) 20 (48%) UACR mg/g (median +/- interquartile range) 740 (68, 1597)
598 (58, 1985) Geometric Mean / Median of UACR mg/g 251 / 250 308 / 567 HbA1c, % (mean +/- SD) 7.2 +/- 1.0 7.1 +/- 1.0 15
Current Enrollment Status & Completion Expectations st nd ACTIVE
COHORT 1 2 REACT REACT Active n = 41 st Before 1 Injection: 2 subjects withdrew Injection Injection 39 EOS nd Before 2 Injection: 4 subjects EOS** as per protocol, 33 1 subject expired, 1 started dialysis 39 33 29 21 (+ 4)* nd Before
12-month follow-up after 2 injection: 2 R 29 subjects expired, 2 subjects withdrew st nd 1 2 1:1 nd REACT REACT Before 24-month follow-up after 2 injection: 3 21 EOS subjects EOS as per protocol, 1 subject started Injection Injection
dialysis, 4 subjects remain enrolled but have not reached 24-month follow-up 34 26 11 (+ 9)* Deferred n= 42 DEFERRED COHORT Before cross-over: 7 subjects EOS as per protocol, 1 34 subject started dialysis Rates of drop-out due to death or
dialysis are typical for advanced CKD nd Before 2 injection: 4 subjects EOS as per protocol, 26 1 subject expired, 3 started dialysis 13 patients remain on study (4 in Active cohort, 9 in Deferred cohort) nd Before 12-month follow-up after 2
injection: 2 All patients expected to complete the study by end of 2023 11 subjects EOS as per protocol, 2 subjects expired, 2 subjects started dialysis, 9 subjects remain enrolled Final study results anticipated in 1H 2024 but have
not reached 24-month follow-up * Subjects pending last eGFR measurement. EOS = End of Study 16
No REACT-related SAE's Identified in RMCL-002 BIOPSY REACT
INJECTION # of patients (%) # of patients (%) ADVERSE EVENT (N=83)* (N=132)* Hematoma 1(1.2) 1(0.8) Pain 0 3(2.3) Hematuria 0 0 Transfusion 0 1 (0.8) Surgical Intervention 0 0 Death 0 0 Acute Kidney Injury 0 1(0.8) CKD progression 0 1(0.8) Renal
vascular disorder 0 1(0.8) Kidney fibrosis 0 1(0.8) *All events are based on sponsor assessment of causality No REACT-related serious adverse events were observed Procedure-related serious adverse events were observed in 6/83 subjects including 1
participant who experienced a hematoma, transfusion, and acute kidney injury. A needle design change was implemented after this event 17
Active Cohort Patients Showed No Clinically Meaningful Active Patients
(N = 39) Effect After 1st Injection vs Deferred Patients on SOC (N = 40) Average Change in eGFR eGFR Decline Over 30 Months Screening 1st Inj 1st Inj + 3m 2nd Inj 2nd Inj + 3m 2nd Inj + 6m 2nd Inj + 9m 2nd Inj + 12m 2nd Inj + 15m 2nd Inj + 18m
Follow-up Follow-up Follow-up Follow-up Follow-up Follow-up Follow-up
____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Screening Biopsy Obs 3m Obs 6m Obs 9m Obs 12m 40 Change in Average eGFR in Active Cohort vs Deferred Cohort on SOC 37.4 st st nd nd nd nd nd nd nd nd nd The Active Cohort showed a 35 1 Inj 1 Inj 2 Inj 2 Inj 2 Inj 2 Inj 2 Inj 2 Inj 2 Inj 2 Inj 2 Inj
+ 3m + 3m + 6m + 9m + 12m + 15m + 18m + 21m + 24m 33.9 32.8 cumulative change in average Biopsy Obs 3m Obs 6m Obs 9m Obs 12m 31.7 32.0 2 eGFR of -3.2 ml/min/1.73m Active Cohort 30 after 30-months; 28.4 Deferred Cohort 32.8 25 The Deferred Cohort,
receiving 30.9 31.8 32.8 N = 39 39 31 33 29 26 21 15 12 12 standard of care, showed a 29.6 N = 40 40 38 35 39 39 31.8 28.4 cumulative change in average 29.6 20 27.9 -6.0 -3.0 0.0 3.0 6.0 9.0 12.0 15.0 18.0 21.0 24.0 2 eGFR of -3.4 ml/min/1.73m
Months Standard of Care after 12-months. Data points are mean +/- SEM ; Data as of August 1, 2023 18 2 eGFR (ml/min/1.73m ) 2 eGFR (ml/min/1.73m )
Deferred to Cross-Over Patients Showed Preservation of eGFR after REACT
Injection Average eGFR in Deferred Cohort: SOC followed by REACT Treatment Average eGFR of the Deferred cohort was nd st nd nd nd 1 Inj 2 Inj 2 Inj 2 Inj 2 Inj st nd 1 Inj 2 Inj 31.8 at baseline + 3m + 3m + 6m + 9m + 12m Biopsy Obs 3m Obs 6m
Obs 9m Obs 12m vs 28.4 at 12 months Standard of Care REACT Injections & Follow-Up [absolute difference of -3.4 2 ml/min/1.73m over 12 months ] 28.8 st Average eGFR at 1 injection after 28.4 eGFR ACR eGFR ACR cross-over was 28.8 Deferred
SOC Patients 31.8 330 -- -- vs Deferred Cross-Over Patients -- -- 28.8 250 28.6 at 18 months [absolute difference of -0.2 2 ml/min/1.73m over 18 months] Data as of August 1, 2023 19 2 eGFR (ml/min/1.73m )
Post-Hoc Analysis of All Subjects who Received at Least One Injection
37% of subjects (27 / 73) had preservation of eGFR during 30 months of follow-up All Subjects who Received at Least One Injection with REACT Grouped into Subjects with an 18-month individual slope in eGFR 0 (n=27) versus REACT treated
subjects with 18- Subjects with an 18-month individual slope in eGFR < 0 (n=46) month individual eGFR Slope 0 Average eGFR in REACT Treated Subjects had a change in average eGFR of 2 -0.5 ml/min/1.73m Baseline CKD Stage CKD Stage,
% 3A 3B 4 [56% of these subjects had eGFR slope 0 7% 37% 56% Stage 4 CKD] eGFR slope < 0 4% 55% 41% 31.1 REACT treated subjects with 18- 30.6 month individual eGFR Slope < 0 30.8 eGFR ACR had change in average eGFR of eGFR slope
0 31.1 164 25.3 eGFR slope < 0 30.8 440 2 -5.5 ml/min/1.73m [41% of these subjects had Stage 4 CKD] Months Data as of August 1, 2023 20 2 eGFR (ml/min/1.73m )
Post-Hoc Analysis of All Subjects who Received at Least One Injection
37% of subjects (27 / 73) had preservation of eGFR during 30 months of follow-up All Subjects who Received at Least One Injection with REACT Grouped into Subjects with an 18-month individual slope in eGFR 0 (n=27) versus Subjects with an
18-month individual slope in eGFR < 0 (n=46) REACT treated subjects with 18- month individual eGFR Slope 0 Average Change from Baseline in eGFR in REACT Treated Subjects had an average change from baseline in eGFR of Baseline CKD
Stage 2 CKD Stage, % 3A 3B 4 -2.8 ml/min/1.73m eGFR slope 0 7% 37% 56% at 30 months eGFR slope < 0 4% 54% 41% REACT treated subjects with 18- month individual eGFR Slope < 0 -2.8 eGFR ACR had an average change from eGFR slope 0
31.1 164 baseline in eGFR of eGFR slope < 0 30.8 440 -7.6 2 -7.6 ml/min/1.73m at 30 months Months Data as of August 1, 2023 21 2 eGFR (ml/min/1.73m )
Subgroup Analysis of Diabetic Patients with CKD Stage 4 and Class A3
Albuminuria* Stabilization of Kidney Function in Active (n=13) and Deferred (n=10) Patients at 12 months vs SOC Avg Change in eGFR from Baseline In Active vs Deferred Patients on SOC Avg Change in eGFR from Baseline in Cross-Over vs Deferred