Mati Therapeutics
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Transcript of Mati Therapeutics
¡ Only 25% of patients properly administer their medication (Robin, 2009) and nearly 50% of patients are non-compliant and discontinue therapy within 6 months (Nordstrom, 2005)"
¡ Many patients with physical and emotional limitations are unable to use eye drops"
¡ Only 8% of the original eye drop is present in the tear film 5 minutes after instillation due to tear film turn over, (Mindel, 1995) which results in peaks and troughs of drug delivery"
"¡ Commonly use preservatives in concentrations that can cause epithelial
toxicity"
¡ For many patients eye drops reduce quality of life"
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¡ Five main challenges all sustained delivery platforms must overcome:"§ Consistent long term efficacy ↔ Consistent treatment effect"§ High retention rates"§ Ease of use, replacement and acceptance for years of administration"§ No residual carrier left behind that cannot be easily removed"§ Pathway of reimbursement for the patient and the physician for the insertion of the delivery
device "
¡ Invasive procedures vs non-invasive!§ Duration of effect – "
▪ Non-surgical procedures given quarterly demonstrate good acceptance from patients and physicians."
▪ Surgical procedures may need a much longer duration of action and more advanced disease state to justify the risk of possible complications."
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¡ Physician perspectives: "§ Are there any trade offs on safety or efficacy compared to drops?"§ Ease of insertion/removal"§ Convince patient to accept and tolerate""
¡ Patient perspectives: "§ Belief that treatment is as efficacious as drops"§ Comfort/tolerability "§ Low side effect profile"§ Cost"
¡ Mati is plans to enter Phase III trials in 2015 with “The Evolute®” a minimally invasive sustained delivery platform using punctal plugs to deliver drugs - initially for glaucoma"§ Alternative delivery methods to eye drops have been explored for decades in order to better
titrate dose delivery and increase patient compliance"
¡ First product candidate in the Evolute® platform will be latanoprost (Xalatan®)"
¡ Potential advantages of the Evolute® over currently available eye drop therapies:"§ Improves patient compliance by eliminating the need for patients to self-administer their
medication"§ Provides consistent drug delivery – avoiding over and under dosing of eye drops"§ Potential for more consistent IOP control – reduction of peak/trough effects"
Proprietary plug Drug eluting core
Drug Core
Polymer Sleeve
Cyanoacrylate Film
Drug Insert Slot
Punctal Plug Delivery System
Upper or superior puncta
Lower or inferior puncta
"¡ Program initially started at QLT Inc. in 2007"
§ Completed multiple Phase II dose-ranging trials in 570 patients"▪ 2007 Initial efficacy of ≈ 3mmHg"▪ Undertook extensive additional drug delivery development"
▪ Current formulation yields 5-6mmHg reduction in IOP over 12 weeks"§ Completed more than 70 iterations of the device design (without drug) in over
1,000 subjects"▪ 2007 Initial retention rates of 47%"▪ Additional investment/development into novel plug design to increase retention"
▪ Current Evolute® design has 92% retention rate over 12 weeks"
¡ Current Program Status:"§ Manufacturing scale up in anticipation of starting Phase III pivotal trial in 2015""
¡ 10 Clinical Trials with 578 patients treated""¡ Exposure to treatment greater than 6 months in some patients""
Concentration of Latanoprost " 3.5µg! 14µg! 21µg! 44µg! 81µg! 95µg! 141µg! 190µg! " # Patients! # Patients! # Patients! # Patients! # Patients! # Patients! # Patients! # Patients! Total!Pilot! 5" " 5!Glau 02! 21" 19" 21" " 61!Glau 03! 60" 53" " 113!Glau 04! 40" " 40!Glau 05! 32" " 32!Glau 07! 83" 83!Glau 08! 15" " 15!Glau 11! " 95" 95!Glau 12! " 57" 57!Glau 13! " " " " " 77" " " 77!Total! 21! 19! 26! 132! 68! 160! 95! 57! 578!
-‐6.09 -‐5.35 -‐5.44
-‐5.07 -‐5.56
-‐4.88 -‐5.3
-‐5.06
-‐7
-‐6
-‐5
-‐4
-‐3
-‐2
-‐1
0 WK 1 WK 2 WK 3 WK 4 WK 6 WK 8 WK 10 WK 12
95% CI* Wk 4: (-‐6.11, -‐4.04), Wk 8: (-‐5.77, -‐3.99), Wk12:(-‐6.20, -‐3.93)
Chan
ge in
IOP (m
mHg)
*95% CI excludes 0, indicating a p-‐value of <.05 All IOP included, regardless of plug loss/removal
Adverse Event Percentage
Lacrimation 13.1%
Eye Pruritis 10.7%
Conjunctival Hyperemia 7.6%
Punctate Keratitis 6.7%
Eyelid Erythema 1.7%
Photophobia 0.5%
All Studies at 95µg Plug Concentration or Less, N=421
Serious AEs Serious Adverse Event Occurrence
Skin Erosion 1 patient
Systemic 2 patients
¡ Moving toward initiation of Phase III trial for latanoprost in 2015"
¡ Multiple product opportunities for development from this platform"§ Allergic conjunctivitis – mast cell stabilizer/antihistamine "§ Anti-inflammatories – steroids and NSAIDs"§ Glaucoma – Additional PGs, Beta-Blockers, Alpha 2s, CAIs, + New compounds"§ Dry Eye "
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¡ Consistent long term efficacy ↔ Consistent treatment effect (5-6mmHg over 12 weeks)"
¡ High retention rates (92%)""
¡ Duration of effect – 12 weeks""¡ Relatively easy to insert and remove "
¡ Good patient tolerability"
¡ Preservative-free plateau of sustained drug delivery"
¡ Extensive intellectual property with 40 patents issued"
¡ A platform technology suitable for multiple therapies"
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