13
Jonathan H. Talamo, M.D. Chief Medical Officer 1 Sustained Intravitreal Drug Delivery OIS at ASRS - August 8, 2016

RETINA COMPANY SHOWCASE- Ocular Therapeutix

Embed Size (px)

Citation preview

PowerPoint Presentation

Jonathan H. Talamo, M.D.Chief Medical Officer1Sustained Intravitreal Drug DeliveryOIS at ASRS - August 8, 2016

Forward-Looking Statements2This presentation contains forward-looking statements about future expectations, plans and prospects for the Company, including statements about the development and regulatory status of the Companys product candidates, such as the Companys expectations and plans regarding regulatory submissions for and the timing and conduct of clinical trials of DEXTENZA for post-surgical inflammation and pain, DEXTENZA for allergic conjunctivitis, DEXTENZA for dry eye disease and OTX T-P for glaucoma and ocular hypertension, the ongoing development of the Companys sustained released hydrogel depot technology, pre-commercial activities, the potential commercialization of DEXTENZA, the potential utility of any of the Companys product candidates, the advancement of the Company's other product candidates and earlier stage pipeline, future sales of ReSure Sealant, the sufficiency of the Companys cash resources and other statements containing the words "anticipate," "believe," "estimate," "expect," "intend", "goal," "may," "might," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Such forward-looking statements involve substantial risks and uncertainties that could cause Ocular Therapeutixs clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, those related to the timing and costs involved in commercializing ReSure Sealant and DEXTENZA, the initiation and conduct of clinical trials, availability of data from clinical trials and expectations for regulatory submissions and approvals, the Companys scientific approach and general development progress, the availability or commercial potential of the Companys product candidates, the sufficiency of cash resources and need for additional financing or other actions and other factors discussed in the Risk Factors section of the Companys filings with the Securities and Exchange Commission, including the Companys most recent Annual Report on Form 10-Q. In addition, the forward-looking statements included in this presentation represent the Companys views as of the date of this presentation. The Company anticipates that subsequent events and developments will cause the Companys views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Companys views as of any date subsequent to the date of this presentation.

2

Proprietary Hydrogels Ocular Therapeutix and other companies with licensed technologyAcross multiple specialtiesMillions of patients treated

Controlled ReleaseMultiple assets in clinical developmentDEXTENZA post-op pain*allergy dry eyeOTX- TP glaucomaOTX-IV protein-based (anti-VEGF)Tki (anti-VEGF/PDGF)

Ocular Therapeutix Expertise3

*NDA pending resolution of CRL

Ocular TherapeutixIntravitreal Depot Technology4

Fine needle injection (25-27g)Compact geometry (designed to avoid optical impact)Payload designed for 6-month deliverySustained, consistent therapeutic levels (zero-order kinetics) in pre-clinical testingBiocompatible and absorbableStrong IP (potential commercial viability)

Ocular Therapeutix depot technology has been tested with a range of anti-angiogenesis drugs in multiple preclinical models

Depot formats to scale

Ocular Therapeutix technology provides a sustained release vehicle designed to work well with common intravitreal injection practice and with known anti-angiogenesis drugs

4

Posterior Segment (OTX-IV)5

ProteinTherapeuticsPursuing partnershipDemonstrated pre-clinical:Protein stabilityRelease profileHydrogel Tolerability

Small MoleculeDrugsTyrosine KinaseInhibitors (TKIs)Pursuing internal developmentDemonstrated pre-clinical:PKPDHydrogel Tolerability

Help

5

Anti-Angiogenesis StrategiesAntibody Drugs6Antibody drugs bind angiogenic growth factors before they reach their receptorsTKIs prevent downstream activity by inhibiting kinases associated with the receptors

TKIs

Endothelial Cell CytoplasmTyrosine KinaseInhibitor Drugs

Antibody drugs act to intercept VEGF, PDGF to prevent engagement with their receptors: VEGFR2, PDGFRTKIs inhibit the activity of kinases associated with VEGFR2, PDGFR

6

Implant resides free floating within the vitreousDissolves after 6-7 months Other intravitreal implants use rigid plastics, such as PLA, or non-degradable materialsOTX-BIV Bevacizumab-loaded Coil

Coiling action forms compact depot in situDepot presents a smooth, hydrophilic, biocompatible surface to tissuesDepot is soft, lubricious biodegradable hydrogel composed of >50% drug71 mm1 mmFiber hydrates and coils as it exits needle

Ocular Therapeutix has recently developed a proprietary technology for a coiling fiber depot that forms a compact shape in situ after ejection from a needle. This is a soft, smooth and lubricious hydrogel, containing embedded drug particles.

7

Rabbit VEGF Challenge ModelOTX-BIV showed continued inhibition up to 12 weeks compared to less than 6 weeks from single human Avastin dose (1.25mg)Control EyeNo Inhibition Leakage score = 4Fluorescein leaking from vesselsRepresentative FA ImagesOTX-BIV suppressed vascular leakage for 3 months8

OTX-BIV Eye 1 monthInhibitionLeakage score = 1OTX-BIV

We have used a modification of a VEGF angiogenesis induction model in dutch belted rabbits to determine if the anti-angiogenic activity can be sustained beyond the normal Avastin formulation. This model uses repeated challenges at various time points following the single injection of the test article - as long as the rabbits remain protected from VEGF. This particular bevacizumab depot was designed to deliver for 3 months.

8

OTX-IV Anti-VEGF Release Profiles

Highly stable in hydrogel

Meets 4-6 month target

ELISA shows continued activity at 4-6 months

We have worked with several antibodies, including anti-angiogenic antibody drugs. The hydrogel has been found to work with a wide molecular weight range from Fab fragments to full antibodies. Aggregation is the first form of protein change seen, in which antibody molecules reversibly join to form mostly dimers, and some trimers. These aggregates are referred to collectively as high molecular weight species. They are not formed from the PEG vehicle. The anti-VEGF molecules we have tested have shown good stability, as evidenced by this low aggregation, which has been minimal and does not result in loss of protein activity.9

Previous TKI Clinical AttemptsChallenges with oral or eye drop formulations of TKIs:Low solubilityLiquid formulations must be suspensions Low bioavailability from drops, injections problematicOff target effects of systemic administrationShort half-life of dissolved drug in eye (hours not days) quickly clearedCompanyDrugFormPhaseDateTargegenTG100801Drop BIDI2007TargegenTG100801Drop BIDII2010GSKPazopanibOral (15mg/day)I/II2012GSKPazopanibDrops (5mg/ml)I/II2013GSKPazopanibDrops (10mg/ml)I/II2014BayerRegorefanibDrops IIa/IIb 2015PanOpticaPAN90806DropsI2016Tyrogenex X-82 (CM082)Oral(25mg/day)I2015Tyrogenex X-82 (CM082)OralIIcurrent

Solution: Local AND sustained delivery10

Several attempts have been made to test the safety and efficacy of TKIs in human trials. In all cases the TKIs were administered as drops or tablets. Several other companies have done extensive animal testing, including intravitreal injection. Our intravitreal sustained delivery technology is unique among the approaches that have been made to date.

10

OTX-TKiIV DL-AAA Rabbit Model 11

Continuous leakage model - measured by fluorescein angiographyAvastin injectionOTX-TKiIV*Pre- injection2 weeks8 weeks

Avastin leakage in resumed at 8 weeks while OTX-TKiIV was still effective (ongoing)*Also effective in VEGF challenge model (rabbit) through 6 months

OTX-IVTolerability @12 Weeks (rabbit)12

Score (0-5)MeanSDVitreous chamber inflammation 0.200.15Retinal, scleral or episcleral inflammation0.280.21Fibrosis around the injected material0.170.14

Histopathology ScoresScoreDescription0No change; normal1Rare foci of change; Minimal2Mild diffuse change or more pronounced focal change3Moderate diffuse change4Marked diffuse change5Severe diffuse change

Hydrogel residueNo inflammatory cellsBlank depot suspended in vitreous at 12 weeks with no associated inflammation

Compact, resorbable depots designed to avoid optical side effectsLarge drug payloads possible (protein and Tki)Tolerability of vehicle through 12 weeks (protein and Tki)Protein delivery for 4-6 months in vitro (4 anti-VEGF proteins)OTX-TKiIV shows robust effect in 2 animal models as long as 6 monthsHydrogel platform used in other FDA-approved and currently marketed medical products, strong IP

OTX-IV Summary13

14