Arsanis: Genetic Mutations In Cxcr4 Create Abnormal Trafficking Of White Blood Cells (Wbcs)

The following excerpt is from the company's SEC filing.

WHIM Phase 2 Study: Assess Neutrophil Counts Biomarker “Time Above Threshold” Metric Objective: Increase Daily Neutrophil Counts (ANC) Above Threshold As Measured Over 24 hours: Time Above Threshold (“TAT”) Intra-Patient Dose Escalation Open label 50 mg to 400 mg once daily (QD) n = 8 patients Inclusion Neutrophil count: ANC ≤400/μL and/or Lymphocyte count: ALC ≤650/μL or both Endpoints & Assessments Safety (infections, warts), pharmacokinetics (PK) / pharmacodynamics (PD) Biomarker: 24-hr Blood Counts of Neutrophils– Time (hrs) Above Threshold HOURS “TAT”(hours) Threshold (500 cells/ul) Inclusion Criteria: WHIM patient ANC ≤400/μL; “TAT” baseline ~ 0 NEUTROPHIL COUNT (ANC) Cells/uL 0 hours baseline 24 hours maximum < TAT < Treatment Goal

Phase 2: Achieved Maximum TAT In Most Patients Neutrophil and Lymphocytes Mobilized; Pan-Leukopenia Addressed Threshold is 500 cells/mL The three pts below threshold had dose increased to 400 mg QD 400 mg QD (n=3) Assessments Result Neutrophil Counts > Threshold 5 of 7 patients (71%): maximum TAT Lymphocyte Counts > Threshold 6 of 7 patients (85%): maximum TAT Safety Acceptable; no Grade 3/4 400 mg QD: Phase 3 Pivotal Trial for Patients > 12 years of age Patients Started with an ANC of 50 – 200 cells/mL Prior to Treatment 300 mg QD (n=7)

Dramatic Reduction in Wart Burden Through 55 Weeks Reductions in Infections Rate Compared to Historical Rates 1. Dale et al, ASH, 2019; 2. McDermott, et a. Blood, 2014. Minimal infections in three patients dosed for over 9-months (0.08 infections/pt/month)1 Historical infection rates reported in WHIM (0.37 infections/pt/month)2 Infection Rates Pre-Treatment 55 weeks Post-treatment Pre-Treatment 55 weeks Post-treatment

Phase 3 Trial in WHIM Syndrome – Expected 2Q19 Initiation Meets entry criteria X4P-001 (n=9) Placebo (n=9) 52 weeks Establish AUC Baseline 1:1 Random-ization Roll-over to Open-label Study 400 mg QD dosing in patients 12 years of age or higher Primary endpoint: biomarker of neutrophil count time above threshold (‘TAT’) where the threshold is defined as 500 cells/uL Secondary endpoints include infection rates and wart burden assessments

Primary Immunodeficiency Label Expansion : Phase I Trial in Severe Congenital Neutropenia Rare blood disorder Characterized by abnormally low levels of certain white blood cells (neutrophils <1,500 cell/ul)1 From birth, fevers, severe bacterial infections (at times life-threatening), pneumonias, oral ulcers, premature tooth loss Treatment options: antibiotics and G-CSF Prevalence estimated 2,000-3,000 patients (US & EU)2 Genetic drivers: May be inherited as either an autosomal dominant or an autosomal recessive genetic trait Many cases of SCN are the result of spontaneous, random mutations Phase 1 trial planned for 2019 Designed to determine the genetic profile of adult SCN patients and assess/correlate their pharmacodynamic response to mavorixafor Oral ulcers Chronic G-CSF Injections 1. 2.

CXCR4 in Cancer: Waldenström’s Macroglobulinemia (WM) Rare Form of Non-Hodgkin’s Lymphoma Estimated prevalence of >13,000 in US and EU1 Annual incidence: 1000-1500 in US2; ~1,800 in EU3 Signs and Symptoms Elevated IgM and other blood-markers Hepatomegaly, splenomegaly, skin purpura ~8-year survival rate post-diagnosis Current Treatment Imbruvica ($136,000 per year) Chemo and Rituxan in certain lines/settings Mechanism: Genetic Drivers in WM >90% have mutations in MYD88 gene 30-40% have WHIM-like mutations in CXCR4 gene Sources 1Prevalence estimate mathematically as incidence x median Survival X 50% (1/2 living and ½ dead at 8 years); Incidence derived mathematically as Prevalence/ 50%/ 8 years 2Sekhar J, Waldenström macroglobulinemia: a Surveillance, Epidemiology, and End Results database review from 1988 to 2005. Leuk Lymphoma 2012;53(8):1625-1626 3 (prevalence estimated at 1/102,220 for EU)

CXCR4WHIM R/R Waldenström’s: Poor Clinical Outcomes vs. Wild-type Phase 1/2 Study Targets CXCR4-Mutant Population Very Good Partial Response (VGPR) Rates: 9.5% vs. 44.4% for wild-type; no Complete Responses (CRs) in either1 Median time to major response of 6 months vs. 2 months for wild-type1 Median Progression Free Survival (mPFS) for CXCR4WHIM is less than half that of mPFS for wild-type 2 ~4-fold likelihood ibrutinib discontinuation in CXCR4WHIM WM3 1. Table Recreated from: Treon et al, EHA 2018 2. Treon et al, EHA 2018 ; 3. Gustine J. Am J Hematol. 2018. Inclusion: Patients with MYD88 + CXCR4 mutations who have failed prior Rx Design: Multinational Phase 1/2 of mavorixafor in combination with ibrutinib 3X3 dose escalation in combination; then expansion Endpoints: safety, PK/PD, VGPR and CR rates, other Expected to commence in 2019 Planned Waldenström’s Trial: Double-Mutant R/R WMs Response Profile in R/R WM

IO Strategy: Goal of Leveraging Biological Expertise Via Partnering Completed Trials Demonstrate Single Agent Activity & Proof of Mechanism Phase 1b In Treatment Naïve Melanoma Phase 1b In Progressing RCC w/Opdivo On-Going Phase 2a ccRCC Trial: Mavorixafor + Axitinib 65-patients; multi-national, fully enrolled Assessment: mPFS Benchmark to beat: 4.8 months mPFS with axitinib in patients with immediate prior TKI Data expected: 2H 2019 Strategy: Identify strategic collaborators to advance in IO; keying off data readout

Epidemiology Suggests Significant Market Opportunity Partnering with World Class Organizations to Increase Awareness in Primary Immunodeficiencies 1. Represents CXCR4-mutatant patients; 30% to 40% of total WM estimate of 13,000 patients Clinical Epidemiology (Estimated patients in US & EU) 2,000 – 3,000 Severe Congenital Neutropenia (SCN) 4,000 – 5,000 Waldenström’s Macroglobulinemia (WM) 1 1,000 – 2000 WHIM Syndrome

Significant Progress Expected 2019 to 2021 Target Date Milestones 2H19 Phase 2a ccRCC PFS data readout Mid 2019 EMA Orphan Drug Designation for WHIM 4Q19-1Q20 WHIM patient identification update 2019 Commence Phase I trial in SCN 2019 Commence Phase 1/2 in Waldenstrom’s 1H20 New pipeline molecules: 002 and 003 INDs Mid 2020 Phase 1 Trial in SCN: topline results Mid 2020 WHIM Phase 2 OLE – Updates 2H 2020 Phase 1/2 in Waldenstrom’s– Safety, Dose and Activity 2020 WHIM Ex-Vivo Fitness Study Results 2021 Phase 3 Trial in WHIM – topline results


The above information was disclosed in a filing to the SEC. To see the filing, click here.

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