Slide 1: Topline ELX-02 Combination Phase 2 Cystic Fibrosis Results
RARE Thinking for RARE Solutions Topline ELX - 02 Combination Phase 2 Cystic Fibrosis (CF) Results September 14, 2022
Slide 2: Forward-looking statements
/ 2 Forward - looking statements This press release contains forward - looking statements within the meaning of the Private Securities Litigation Reform Act of 199 5. All statements other than statements of present and historical facts contained in this press release, including without limitatio n,
Slide 3: Summary of Phase 2 results
/ 3 Summary of Phase 2 results Combination treatment did not achieve statistical significance for efficacy endpoints Assessment of responders shows drug activity for ELX - 02 Higher drug exposure in lung needed to generate therapeutic benefit Path forward in CF to be determined together with the CF
Slide 4: Class 1 CF patients carrying nonsense mutations have the most severe phenotype
/ 4 Class 1 CF patients carrying nonsense mutations have the most severe phenotype CF patients by mutation type 1 • No functional CFTR created • More severe disease presentation • Higher rate of FEV1 decline • No approved therapies • ELX - 02 granted Orphan Drug and Fast Track Designation by FDA Tot
Slide 5: ELX-02 intra-patient dose escalation monotherapy Phase 2 trial results
/ 5 ELX - 02 intra - patient dose escalation monotherapy Phase 2 trial results Change in sweat chloride from baseline in G542X CF patients after 1 week treatment with ELX - 02 (mmol/L)* *Drug response evaluated based on difference between end of the treatment period to the average baseline for each
Slide 6: ELX-02 and ivacaftor combination in Class 1 CF Phase 2: Study Design
/ 6 ELX - 02 and ivacaftor combination in Class 1 CF Phase 2: Study Design Expanded 5 - week Phase 2 trial to evaluate FEV1 and safety in combination with ivacaftor Inclusion Parameters Criteria Genotype All Patients with nonsense mutations Age All patients >12 years FEV1 >40% n = 16 * ELX - 02 1.5
Slide 7: Cumulative safety experience across all Phase 2 patients
/ 7 Cumulative safety experience across all Phase 2 patients * Patient had an undisclosed history of tinnitus No systemic safety signals observed for ELX - 02 No ELX - 02 related serious adverse events (SAEs) ELX - 02 was well tolerated at 1.5 mg/kg dose across Phase 2 patients (n=31) – Combination
Slide 8: SCC and FEV1 change from baseline at Day 7 and Day 35
/ 8 SCC and FEV1 change from baseline at Day 7 and Day 35 Mean SCC from baseline Mean FEV1 change from baseline Error bars: Standard deviation Combination of ELX - 02 with ivacaftor did not achieve statistical significance for efficacy endpoints Day 7 n=14 Day 35 n=12 -10 -8 -6 -4 -2 0 2 C h a n g e
Slide 9: Responder assessment showed drug activity
/ 9 *Am J Respir Crit Care Med Vol 199, Iss 9, pp 1116 – 1126 Responder assessment showed drug activity 70 80 90 100 110 120 130 -15 -10 -5 0 5 10 15 Baseline Sweat Chloride (mmol/L) C h a n g e i n S w e a t C h l o r i d e f r o m B a s e l i n e a t T P 5 D 3 5 ( m m o l / L ) p= 0.00013 Decreasi
Slide 10: SCC at Day 7 and Day 35 by patient
/ 10 SCC at Day 7 and Day 35 by patient High sweat chloride variability confounded activity signal in responders Day 7 Day 35 Increasing response Change in Sweat Chloride from Baseline (mmol/L) SCC at Day 7 Mean (SD) SCC at Day 35 Mean (SD) Responder - 5.2 (3.5) - 5.5 (4.1) Responder rate 7/14 (50%)
Slide 11: Change in FEV1 from baseline at Day 7 and Day 35 by patient
/ 11 Change in FEV1 from baseline at Day 7 and Day 35 by patient Similar variability in lung function measurement confounded activity signal in responders Day 7 Day 35 FEV1 change at Day 7 Mean (SD) FEV1 change at Day 35 Mean (SD) Responder +4.5 (5.1) +4.0 (4.1) Responder rate 4/15 (27%) 4/11 (36%)
Slide 12: High variability also in G542X rats after SC treatment
/ 12 Nasal potential difference in G542X rats after 7 days of SC ELX - 02 treatment at 12 mg/kg (human equivalent dose of 1.5 mg/kg) Data from Dr. Susan Birket – UAB High variability also in G542X rats after SC ELX - 02 treatment W T V e h i c l e E L X - 0 2 S Q 1 2 m g / k g -15 -10 -5 0 5 C L - -
Slide 13: Swelling response in CF patient organoids with and without ivacaftor
/ 13 Swelling response in CF patient organoids to ELX - 02 treatment with and without ivacaftor* 134 2,739 829 240 3,579 1,447 - 1,000 2,000 3,000 4,000 5,000 6,000 - 5 10 15 20 25 30 35 40 Organoid swelling response after 4 days of treatment (AUC at t=120 mins) Steady state ELX - 02 exposure in lun
Slide 14: Key takeaways
/ 14 Key takeaways Evidence of activity for ELX - 02 observed and shown to be well tolerated with no SAEs Efficacy signal potentially confounded by variability due to low drug exposure Path forward in CF to be determined together with the CF Foundation
Slide 15: Estimated dose to exposure relationship in kidney
/ 15 Estimated ELX - 02 dose to exposure relationship in kidney at 1mg/kg, ng*hour/ml In contrast, high ELX - 02 levels can be easily achieved in kidney 23,658 1,266,000 Plasma Kidney • CF results de - risk current Alport Program • Estimated kidney exposure at 0.75 mg/kg 50 - 100 m M 52X
Slide 16: Milestones over next 12 months
/ 16 Milestones over next 12 months * RDEB/JEB: Recessive Dystrophic/Junctional Epidermolysis Bullosa; FAP: Familial adenomatous polyposis Significant pipeline milestones expected over next 12 months Class 1 Cystic Fibrosis (Inhaled ELX - 02) • Inhaled ELX - 02 IND submission • Inhaled vs. SC in viv
Slide 17: Questions? Answers.
/ 17 Questions? Answers.
Slide 18: Eloxx Pharmaceuticals
Eloxx PHARMACEUTICALS Eloxx