Nexvet Biopharma — ACVIM Forum 2016
65 slides from Nexvet Biopharma's conference presentation, Jun 9, 2016
Slide 1: Monthly injectables for chronic dog and cat pain
Monthly injectables for chronic dog and cat pain Clinical data and discussion ACVIM Forum 2016
Slide 2: Welcome!
Welcome! Introductions and overview
Slide 3: Agenda
Agenda Dr. Jürgen Horn Dr. med.vet, PhD, MBA Overview Prof. Duncan Lascelles BSc, BVSc, PhD, MRCVS, CertVA, DSAS(ST), DECVS, DACVS Chronic pain—management & measurement (dogs and cats) Dr. Colin Giles BVetMed, PhD, MRCVS Ranevetmab – clinical data and background Dr. Jane Eagleson BVSc, MVSc NV-02 –
Slide 4: Forward-looking statements
Forward-looking statements This presentation and other presentations given today contain forward-looking statements. All statements, other than statements of historical facts, contained in these slides and the accompanying oral presentation, including statements regarding our future results of opera
Slide 5: 100% biologics animal health company, focused on targets de-risked by late-stage human data
100% biologics animal health company, focused on targets de-risked by late-stage human data Unique target product profiles: a leap forward for animal health Positive clinical studies (efficacy and safety) for lead program in chronic pain in dogs and cats Clinically validated platform technology for
Slide 6: Therapeutic focus areas
Therapeutic focus areas Nexvet is focused on monoclonal antibodies in four major therapeutic areas: Pain Inflammation Allergy Immuno-oncology Focus on chronic conditions with significant unmet medical need
Slide 7: Targets validated by late-stage human data
Targets validated by late-stage human data Chronic Pain (key target: NGF) Chronic inflammation (key target: TNF) Ranevetmab NV-02 (cat) Lead ID of new candidates based on validated human targets Multiple mAb research candidates targeting TNF Immuno-oncology (key target: PD-1) PD-1 program f Others a
Slide 8: PETization: a platform technology for rapid interspecies mAb design
PETization: a platform technology for rapid interspecies mAb design
Slide 9: PETization: the concept
PETization: the concept Rapid interspecies translation of mAbs that retains affinity, with a lower chance of immunogenicity
Slide 10: PETization: a platform for rapid mAb design
PETization: a platform for rapid mAb design 1. All our mAb research candidates or therapies in development have originated from PETization 2. An algorithm-based approach that converts mAbs from one species to another 3. Proprietary, patent-protected, and clinically validated in three species 4. The
Slide 11: The time for pet biologics is now
The time for pet biologics is now Transforming platform: PETization Nexvet: focused on delivering the therapeutic biologics revolution to veterinary care. ultiple candidates ultiple clinical successes ractive efficacy and safety profiles Indications with significant medical need
Slide 12: Ranevetmab: a novel caninized anti-NGF monoclonal antibody
Ranevetmab | a novel caninized anti-NGF monoclonal antibody for the control of pain associated with osteoarthritis in dogs Background and pivotal study results Dr Colin Giles Vice President – Clinical and Regulatory Affairs June 2016
Slide 13: Special note about therapies in development
Special note about therapies in development The presentations made today include results of clinical trials for the following agents that are currently still in development and not approved for marketing: ranevetmab and NV-02.
Slide 14: Overview and scientific background to ranevetmab
Overview and scientific background to ranevetmab
Slide 15: Ranevetmab: overview
Ranevetmab: overview 100% canine monoclonal antibody against nerve growth factor (NGF) In development as a monthly injectable Parameter Nexvet’s ranevetmab Control of pain associated Lead indication with osteoarthritis Subcutaneous injection Dosing once every 4 weeks No adverse safety signals Safety
Slide 16: Nerve growth factor (NGF): an important pain pathway
Nerve growth factor (NGF): an important pain pathway NGF is involved in nerve growth and pain signaling and highly conserved across species Anti-NGF mAbs have demonstrated significant potency in rodents and human trials: and now dogs, cats and horses (Phase II/III) e.g. Pfizer/Eli Lilly studies of t
Slide 17: Ranevetmab: detailed description
Ranevetmab: detailed description Novel biotherapeutic veterinary medicine under clinical investigation for the control of pain associated with OA in dogs Fully caninized“100% dog” monoclonal antibody that neutralizes nerve growth factor(NGF) Produced as a secreted product from a genetically engineer
Slide 18: Proof-of-concept data and pivotal study design
Proof-of-concept data and pivotal study design
Slide 19: Earlier studies demonstrated:
Earlier studies demonstrated: Ranevetmab binds NGF with high affinity and is a potent inhibitor of canine NGF. Ranevetmab does not recruit complement Ranevetmab has high bioavailability following SC injection, a half-life of distribution of approximately nine days and a prolonged duration of effect
Slide 20: Pivotal study design
Pivotal study design Multi-center, placebo-controlled, randomized, and masked Conducted to GCP under a single FDA-concurred protocol DOGS ENROLLED THREE MONTHLY DOSES 12 study sites 6 in U.S., 3 in France, 3 in Germany RANDOMIZED ASSIGNMENT : PLACEBO TREATMENT Veterinary patients with clinical disea
Slide 21: Ranevetmab pivotal study design: FDA-concurred protocol
Ranevetmab pivotal study design: FDA-concurred protocol 3 subcutaneous injections (ranevetmab or placebo), were given at days 0, 28 and 56 Efficacy assessments are made at days 0,14, 28, 56, and 84 Primary efficacy assessment at day 28 Telephone checks at Day 7 and Day 112 (final check) 1 vial per 1
Slide 22: Pivotal study design: CSOM
Pivotal study design: CSOM Client-specific Outcome Measures (CSOM) o Single owner makes all observations o 3 activities specific to their dog o Difficult for the dog or had changed as a result of OA o Measured on a 5 point scale with “0” being no problem and “4” being impossible o A priori success c
Slide 23: Pivotal study design: CBPI
Pivotal study design: CBPI Canine Brief Pain Inventory (CBPI) o Validated assessment method developed by Brown et al 2008, 2013 o Graded on scale of 0 to 10 with “0” being normal and 10 being the most extreme effects o Pain Severity Score (PSS) – 4 individual elements o Pain interference score (PIS)
Slide 24: Population review
Population review o 319 dogs completed screening o 262 dogs enrolled in the study, o 173 treated with ranevetmab o 1 mL per 10 kg SC injection (0.2 – 0.4 mg/kg range) o 89 treated with placebo o Labrador Retriever was most common breed followed by mixed breed o Evaluable population varied by day but
Slide 25: Ranevetmab pivotal safety and efficacy study results
Ranevetmab pivotal safety and efficacy study results
Slide 26: Outcomes: summary
Outcomes: summary Study demographics o 25 female; 115 spayed females; 42 male; 80 castrated males o Age range: 8 months 15 years o Mean age ~ 9 years o Most common breed was Labrador Retriever o Other breeds included (in order of number) Mixed breed, Golden Retriever, German Shepherd, Labrador Retri
Slide 27: Results: CSOM success and global assessment
Results: CSOM success and global assessment Ranevetmab treatment significantly superior to placebo on days 28, 56 and 84 on CSOM success CSOM Global assessment at day 28: significantly more success compared to placebo Remember: success = decrease of 2 in total CSOM score and no increase in any indiv
Slide 28: Statistical results table
Statistical results table Evaluation at Screening Placebo Ranevetmab N 89 173 Mean (SEM) 7.44(0.16) 734(0.10) Min, Max 5,11 5,11 p-value 0.598 Study Day Success/Failure Placebo Ranevetmab Day 14 Success 48/87(55.2%) 107/169 (63.3%) Difference (95% CI) 8.1 (-5.5, 21.7) p-value 0.2354 Day 28 Success 4
Slide 29: Results: CSOM median changes
Results: CSOM median changes Evaluation at Screening Placebo Ranevetmab N 89 173 Mean (SEM) 7.44 (0.16) 7.34(0.10) Min, Max 5, 11 5, 11 p-value 0.598 Study Day Change Placebo Ranevetmab Day 14 Median change -2.00 -2.00 Mean change (SEM) -2.12 (0.25) -2.50 (0.17) p-value 0.1009 Day 28 Median change -
Slide 30: Results: CBPI successes
Results: CBPI successes Ranevetmab treatment significantly superior to placebo on days 14, 28 and 56 (P<0.05) (day 84, P=0.059) = statistically significant difference CBPI success success 30 % 20 10 Day 14 Day 28 Day 56 Day 84 Placebo Ranevetmab
Slide 31: CBPI statistical results table
CBPI statistical results table Study Day Success/Failure Placebo Ranevetmab Day 14 Success 23/85 (27.1%) 74/164 (45.1%) Failure 62/85 (72.9%) 90/164 (54.9%) Difference (95% CI) 18.1 (5.0, 31.1) p-value 0.0237 Day 28 Success 25/81 (30.9%) 78/159 (49.1%) Failure 56/81 (69.1%) 81/159 (50.9%) Difference
Slide 32: Results: CBPI components
Results: CBPI components Pain Severity Score (PSS) Ranevetmab treatment significantly superior to placebo on days 14, 28 and 56 (day 84, P=0.062) Pain Interference Score (PIS) Ranevetmab treatment significantly superior to placebo on days 14, 28 and 56 (day 84, P=0.092) Lower scores mean greater imp
Slide 33: CBPI components results table
CBPI components results table Day Pain Interference Score Pain Severity Score 14 0.0467 0.0042 28 0.0163 0.0024 56 0.0008 0.0003 84 0.0922 0.0623 = statistically significant difference
Slide 34: Outcomes
Outcomes Veterinarian’s assessments Numerically superior to placebo for each composite variable at most evaluation points Statistically significant overall treatment effect for lameness at trot Safety Outcomes No clinically relevant differences observed between placebo and treated groups
Slide 35: Final pivotal study conclusions
Final pivotal study conclusions Ranevetmab administered to dogs at a dose range of 0.2 to 0.4 mg/kg is effective and safe for the treatment of pain associated with OA
Slide 36: Implications for clinical practice
Implications for clinical practice o The prevailing multi-modal approach to managing chronic canine pain does not currently include a monthly subcutaneous injectable therapeutic option o Ranevetmab has been shown to be safe and well-tolerated in multiple studies o The clinical data to date support t
Slide 37: NV-02: a novel felinized anti-NGF monoclonal antibody
NV-02 | a novel felinized anti-NGF monoclonal antibody for the control of pain associated with osteoarthritis in cats Background and pilot study results Dr. Jane Eagleson June 2016
Slide 38: Background and clinical context for NV-02
Background and clinical context for NV-02
Slide 39: NV-02: overview
NV-02: overview 100% feline Parameter Nexvet’s NV-02 monoclonal antibody Control of pain associated Lead indication against nerve with osteoarthritis growth factor Dosing Subcutaneous injection (NGF) once every 4 weeks No adverse safety signals Safety seen In development Numerous statistically as a
Slide 40: NV-02: detailed description
NV-02: detailed description USAN-approved nonproprietary name: frunevetmab Novel biotherapeutic veterinary medicine under clinical investigation for the control of pain associated with OA in cats Analogous cat therapy to ranevetmab in the dog Fully felinized (“100% cat”) monoclonal antibody that neu
Slide 41: Pain relief in the cat: limited options
Pain relief in the cat: limited options No FDA-approved therapies for the treatment of chronic pain in cats Safety concerns around chronic NSAID use in cats especially in the older population where incidence of chronic renal failure is high NSAIDs only approved for short-term use in cats in the U.S.
Slide 42: Proof-of-concept data and pilot study design
Proof-of-concept data and pilot study design
Slide 43: Earlier studies demonstrated:
Earlier studies demonstrated: o NV-02 binds NGF with high affinity and is a potent inhibitor of feline NGF. o NV-02 does not bind complement C1q in vitro. C1q is the first element of the complement cascade. o NV-02 has high bioavailability following SC injection and a half-life of distribution of ap
Slide 44: NV-02 proof-of-concept efficacy and pilot safety studies
NV-02 proof-of-concept efficacy and pilot safety studies o Proof-of-concept efficacy Field study in 32 client-owned cats Single study site o Statistically significant top-line results seen in 3 week CSOM scores and other endpoints out to 5 weeks o No adverse safety signals observed in PoC efficacy s
Slide 45: Dose level and regimen selection
Dose level and regimen selection o Minimum dose of 1.0 mg/kg selected for further investigation based on previous studies o Dose of 1 mL vial per 7 kg (7 mg/mL) selected because high percentage of cats are ? 7 kg o Large breeds and overweight cats > 7kg receive 2 vials. o IV or SC administration – s
Slide 46: Larger exploratory study: the design
Larger exploratory study: the design
Slide 47: Exploratory feline patient study: design
Exploratory feline patient study: design Placebo-controlled, randomized, and masked study at 15 U.S. sites Randomized to 3 treatment groups 126 TWO Group Day 0: Day 28: CATS MONTHLY treatment one treatment two ENROLLED DOSES NV-02 (A) IV SC Both intravenous (IV) and subcutaneous (SC) NV-02 (B) SC SC
Slide 48: Dose range examples
Dose range examples Dose ranged between 1.0mg/kg and 2.8mg/kg Cat weight # of 1mL Effective dose examples units of (kg) 7mg/mL NV-02 2.5 1 2.8mg/kg (minimum) (maximum) 4 1 1.75mg/kg 7 1 1mg/kg (minimum) 8 2 1.75mg/kg 12 2 1.17mg/kg
Slide 49: Study design: key assessments
Study design: key assessments o Owner’s evaluation: CSOM and FMPI o Veterinarian’s evaluation o Samples for hematology/clinical chemistry/urinalysis Day Owner Veterinarian Blood/urine exam sampling (Up to 14 days before Day 0) Screening First treatment 0 14 Second treatment 28 42
Slide 50: Study design: CSOM owner assessment
Study design: CSOM owner assessment CSOM: single owner makes all observations o Owner selects 3 activities specific to their cat that are difficult for the cat or have changed as a result of osteoarthritis o Measured on a 5 point scale with “1” being no problem and “5” being impossible o A priori su
Slide 51: Study design: CSOM owner assessment
Study design: CSOM owner assessment Example CSOM activities: o Full body stretching o Stair climbing o Jumping up to elevated feeding areas o Running while playing with other cat o Jumping off the bed in the morning o Whole body grooming
Slide 52: Study design: FMPI owner assessment
Study design: FMPI owner assessment Feline musculoskeletal pain index (FMPI) o Still under development, not validated o 17 questions on the cat’s behavior scored 1 to 5 o Max possible score is 85 o 4 additional yes/no questions Example questions:
Slide 53: Study design: veterinarian assessment
Study design: veterinarian assessment Orthopedic assessment o Cannot easily measure lameness and weight bearing in cats o Physical examination of appendicular joints and spinal segments o Each limb examined and the joints graded for: Pain (5 point scale) Crepitus (3 point scale) Effusion (3 point sc
Slide 54: Exploratory study outcomes
Nexvet” Exploratory study outcomes
Slide 55: Outcomes: summary
Outcomes: summary In vivo phase completed Cats usually more difficult to enroll and maintain on studies because: o Lower medicalization rates o Intolerance for clinic visits o More difficult to detect pain 126 cats enrolled Analysis populations o 41 placebo o 79-93 % of total enrolled o 42 in NV-02
Slide 56: Outcomes: summary
Outcomes: summary Study demographics o 52 castrated males, 74 spayed females o Age range: 1 year, 0 months 21 years, 10 months o 108 cats weighed ? 7kg (1 vial/dose), 18 cats weighed > 7 kg (2 vials/dose) o Most common breed was non-pedigree domestic shorthair o Other breeds included Siamese, Ragdol
Slide 57: Outcomes: value of IV loading dose
Outcomes: value of IV loading dose o No meaningful difference between IV:SC and SC:SC NV-02 groups o Methodology can detect significant differences between treated and placebo treatments despite small group sizes o High placebo effect seen in cats o Similar to dogs o 45-60% in this study o Tended to
Slide 58: Outcomes: CSOM
Outcomes: CSOM o CSOM % success: NV-02 was numerically superior to placebo at Day 28 onwards and significantly different at Days 42 and 56 o CSOM Global Assessment: NV-02 was significantly different to placebo at Days 28 and 56 (only timepoints where conducted) o Change in median CSOM score: NV-02 w
Slide 59: Outcomes: CSOM
Outcomes: CSOM Combined treatment group p-values Day CSOM CSOM Global Median CSOM success/failure % Assessment score change 14 0.8503 na 0.3595 28 0.1015 0.0134 0.0539 42 0.0479 na 0.0077 56 0.0033 0.0030 <0.0001 = statistically significant difference = close to statistical significance
Slide 60: Outcomes: FMPI
Outcomes: FMPI o FMPI is still evolving as an assessment tool o This study will help inform the development of reliable metrology instruments for cats o Significance was assessed using multiple measures of success o Using a reduction of 10 or more in total score (out of a max possible score of 85) a
Slide 61: Outcomes: FMPI
Outcomes: FMPI Combined treatment group p-values Day FMPI Median FMPI score success/failure % reduction 14 0.6034 0.6468 28 0.4212 0.1461 42 0.0076 0.0002 56 0.0242 0.0160 = statistically significant difference
Slide 62: Other outcomes
Other outcomes Additional FMPI “yes/no” questions o No consistent significant differences between groups o May not be appropriate for measuring efficacy for treatment of pain in the cat Orthopedic (veterinarian’s) assessment o No significant differences between groups o Palpation and measures of joi
Slide 63: Conclusions
Conclusions o NV-02 has potential as a monthly injectable for treatment of pain due to osteoarthritis in cats o No adverse safety signal has been detected to date o Dose of 1.0 – 2.8 mg/kg administered once a month by SC injection is suitable for use in a pivotal efficacy and field safety study in f
Slide 64: Implications for clinical practice
Implications for clinical practice o A monthly subcutaneous injectable for chronic pain would be a novel modality for feline care o Currently no approved drugs for long-term use in the U.S. and most existing treatments come with safety concerns or may have frequent oral dosing requirements that impa
Slide 65: Nexvet
Nexvet Transforming animal medicine