UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, DC 20549

 

 

FORM 8‑K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of

The Securities Exchange Act of 1934

 

Date of Report (Date of earliest event reported): November 20, 2019

 

 

Clearside Biomedical, Inc.

(Exact name of registrant as specified in its charter)

 

 

900 North Point Parkway, Suite 200

Alpharetta, GA 30005

(Address of principal executive offices, including zip code)

 

(678) 270-3631

(Registrant’s telephone number, including area code)

 

N/A

(Former name or former address, if changed since last report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

[  ] Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

[  ] Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

[  ] Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

[  ] Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Securities registered pursuant to Section 12(b) of the Act:

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company           ☒

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒

 

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Item 8.01 Other Events.

 

Clearside Biomedical, Inc. (the “Company”) was recently informed by its commercial contract manufacturer for XIPERE™ (triamcinolone acetonide suprachoroidal injectable suspension), that the U.S. Food and Drug Administration has requested that the manufacturer complete certain manufacturing activities within its facility. These activities are not specifically related to XIPERE, but Clearside expects a delay in the production of the drug product stability data needed to resubmit its New Drug Application (“NDA”). Based on current information from the manufacturer, the Company now expects to resubmit the XIPERE NDA in the second quarter of 2020.

 

On November 20, 2019, members of management of the Company will present at the Stifel 2019 Healthcare Conference on, among other things, the Company’s product candidate pipeline and clinical and regulatory status. A copy of the presentation that is being presented at the conference is available on the Company’s website at www.clearsidebio.com, and is filed as Exhibit 99.1 to this Current Report on Form 8-K, the contents of which are incorporated herein by reference.

 

Item 9.01 Financial Statements and Exhibits.

 

 

 

 

 

 

 

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SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

 

 

 

Corporate Presentation | November 2019 Exhibit 99.1

Forward-Looking Statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Clearside Biomedical, Inc.’s views as of the date of this presentation about future events and are subject to risks, uncertainties, assumptions, and changes in circumstances that may cause Clearside’s actual results, performance, or achievements to differ significantly from those expressed or implied in any forward looking statement. Although Clearside believes that the expectations reflected in the forward looking statements are reasonable, Clearside cannot guarantee future events, results, performance, or achievements. Some of the key factors that could cause actual results to differ from Clearside’s expectations include its plans to develop and potentially commercialize its product candidates; Clearside’s planned clinical trials and preclinical studies for its product candidates; the timing of and Clearside’s ability to obtain and maintain regulatory approvals for its product candidates; the extent of clinical trials potentially required for Clearside’s product candidates; the clinical utility and market acceptance of Clearside’s product candidates; Clearside’s commercialization, marketing and manufacturing capabilities and strategy; Clearside’s intellectual property position; and Clearside’s ability to identify additional product candidates with significant commercial potential that are consistent with its commercial objectives. For further information regarding these risks, uncertainties and other factors you should read the “Risk Factors” section of Clearside’s Annual Report on Form 10-K for the year ended December 31, 2018, filed with the SEC on March 15, 2019, Clearside’s Quarterly Report on Form 10-Q, filed with the SEC on Novmber 8, 2019, and Clearside’s other Periodic Reports filed with the SEC. Clearside expressly disclaims any obligation to update or revise the information herein, including the forward-looking statements, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and by Clearside relating to market size and growth and other data about its industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of Clearside’s future performance and the future performance of the markets in which Clearside operates are necessarily subject to a high degree of uncertainty and risk.

Dedicated to Developing Treatments that Restore and Preserve Vision for People with Serious Eye Diseases Novel, therapeutic platform combines patented SCS Microinjector™ for Suprachoroidal Injection with proprietary drug formulations

Clearside Biomedical: Five Key Investment Themes Proprietary access to the suprachoroidal space Patented technology and delivery approach Large and growing retinal market opportunity Partnering to monetize and expand use of SCS platform Building an internal R&D pipeline

© 2019 Clearside Biomedical, Inc. Exclusive Access to the Back of the Eye Using Clearside’s Proprietary SCS Microinjector™

Ocular Delivery Methods to Reach the Back of the Eye Suprachoroidal Space Injection Intravitreal Injection Broad diffusion to all areas of the eye including the anterior chamber and lens Highly variable drug diffusion across the sclera into the eye Periocular Injection Subretinal Injection Invasive surgery with variable results Specially-designed SCS Microinjector ™ allows for precise delivery into the suprachoroidal space

16 Apparatus using loss-of-resistance technology Administration of any anti-inflammatory drug to the suprachoroidal space by microinjection Methods of treating posterior ocular disorders including macular edema or uveitis Methods using loss-of-resistance technology Apparatus having / methods using an adjustable puncture member Administration of any drug to the suprachoroidal space by microinjection Administration of any drug to the eye by inserting a microinjector into the sclera Strong Intellectual Property Coverage of SCS Platform 3 1 3 2 3 1 3 U.S. Patents Total Expiring between 2027 - 2037 DEVICE PATENTS DRUG PATENTS DISEASE PATENTS

Core Advantages of Treating Via the Suprachoroidal Space Sources: PK = pharmacokinetic | 1. Rai UDJ, Young SA, Thrimawithana TR, et al. The suprachoroidal pathway: a new drug delivery route to the back of the eye. Drug Discov Today. 2015;20(4):491-495. 3. Moisseiev E, Loewenstein A, Yiu G. The suprachoroidal space: from potential space to a space with potential. Clin Ophthalmol. 2016;10:173-178. 2. Chiang B, Jung JH, Prausnitz MR. The suprachoroidal space as a route of administration to the posterior segment of the eye. Adv Drug Deliv Rev. 2018;126:58-66. TARGETED The back of the eye is the location of many irreversible and debilitating visual impairments1 BIOAVAILABLE PROLONGED PK Fluid spreads circumferentially and posteriorly when injected within the suprachoroidal space, bathing the choroid and adjacent areas with drug2 COMPARTMENTALIZED Drug is compartmentalized in the suprachoroidal space, which helps keep it away from non-diseased tissues2 for efficacy for safety for durability

The Suprachoroidal Space & Triamcinolone Acetonide targeted for efficacy PreclinicalClinical Trial n=45 n=10 Percent subjects PEACHTREE Met its Primary Endpoint: Efficacy Data Subjects gaining ≥15 BCVA letters from baseline, % Source: Gilger, et al, Treatment of Acute Posterior Uveitis in a Porcine Model by Injection of Triamcinolone Acetonide into the Suprachoroidal Space Using Microneedles, Physiology and Pharmacology p<0.001

The Suprachoroidal Space & Triamcinolone Acetonide compartmentalized for safety Values are area under the curve ratios (SCS / IVT) over 91 days in rabbit eyes 12 Sclera/Choroid/ Outer Retina 1 Neural Retina 0.03 Iris and Ciliary Body 0.002 Lens Drug not detected in the aqueous from SCS injection PreclinicalClinical Trial Source: Edelhauser HF, et al. ARVO Annual Meeting. 2013. | Phase 3 clinical trial data. PEACHTREE IOP AE Rates: Safety Data All 160 Patients Rescued Control Patients Percent Subjects N=11/96 N=10/64 N=10/37 IVT or periocular steroid rescue

The Suprachoroidal Space & Triamcinolone Acetonide prolonged PK for durability PEACHTREE MAGNOLIA CLS-TA Injection #2 MAGNOLIA: Durability Data PreclinicalClinical Trial Sources: Gilger, et al, Treatment of Acute Posterior Uveitis in a Porcine Model by Injection of Triamcinolone Acetonide into the Suprachoroidal Space Using Microneedles, Physiology and Pharmacology | Phase 3 PEACHTREE data; MAGNOLIA data CLS-TA Injection #1

Two-Prong Corporate Strategy Leveraging Clearside’s Proprietary Suprachoroidal Space (SCS) Injection Platform Grow our internal R&D pipeline Small molecules Gene therapy Create strategic external collaborations Commercialize lead asset Enable access to the SCS

STUDY DRUG INDICATION CLS-AX (suprachoroidal axitinib) Wet AMD Gene Therapy Inherited Retinal Disease Pipeline of SCS Treatments with Broad Applicability PRECLINICAL IND-Enabling PHASE 1/2 PHASE 3 NDA PARTNER INDICATION BAUSCH HEALTH XIPERE™ (macular edema associated with uveitis) AURA BIOSCIENCES Ocular Oncology / Choroidal Melanoma REGENXBIO Wet AMD, Diabetic Retinopathy PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA PARTNER PROGRAMS using SCS Microinjector™ IND mid-2020 Q2 Resubmission

Three Partnering Deals to Drive Growth Eliminated the inherent risks and financial investment related to building and maintaining a commercial infrastructure Validated our investment in suprachoroidal delivery using our SCS Microinjector Eligible to receive >$200 million from the three partnerships in potential development and sales milestones, and potential royalties to fund our internal R&D pipeline Expanded our overall internal and collaborative product development pipeline

The Opportunity: XIPERE Commercialization & Development Exclusive license for XIPERE commercialization and development in the U.S. and Canada Right to develop and commercialize XIPERE for additional ophthalmic indications including diabetic macular edema and retinal vein occlusion Right to develop and commercialize a specified set of corticosteroids and non-steroidal anti-inflammatory drugs in ophthalmology using our proprietary SCS Microinjector The Terms: $5 million upfront Up to $15M in FDA approval and pre-launch milestones Up to $56M in milestone payments Tiered royalties on net sales Maximizing Commercial Potential of XIPERE ™

Pivotal Phase 3 PEACHTREE trial met its primary endpoint MAGNOLIA Phase 3 extension study demonstrated durability If approved, XIPERE would be the first therapy for this indication Expect to resubmit NDA in Q2 2020 with additional stability data and device use assessment Novel Approach to Targeting Uveitic Macular Edema XIPERE™ is an investigational product under FDA review. | BCVA = Best Corrected Visual Acuity

The Opportunity: Gene Therapy Exclusive worldwide rights to our SCS Microinjector for delivery of adeno-associated virus (AAV)-based therapeutics to the suprachoroidal space to treat wet AMD, diabetic retinopathy and other conditions for which anti-VEGF treatment is the standard of care Delivery of gene therapy through the SCS may provide a targeted, in-office, non-surgical treatment approach option Encouraging preclinical results delivering RGX-314 into the SCS The Terms: $2 million upfront / exercise of option Up to $34M in development milestones across multiple indications Up to $102M in sales milestones Royalties on net sales of products using SCS Microinjector Enabling In-office Delivery of Gene Therapy

The Opportunity: Ocular Oncology Non-surgical alternative to intravitreal delivery of Aura’s oncology drug candidates via our SCS Microinjector Choroidal melanoma is the most common, primary intraocular tumor in adults Expect Aura to submit an IND amendment and initiate a clinical trial using our SCS Microinjector in the first half of next year The Terms: Potential future financial upside for Clearside from pre-specified development and sales milestones Royalties on net sales of products using SCS Microinjector Optimizing Ocular Oncology Drug Delivery with SCS Microinjector™

Dr. Thomas Ciulla Chief Medical Officer

Opportunity Concentrated distribution Protection of off-target tissues Migration of small molecules into the anterior chamber Extended duration of action Broad Applicability of SCS Injection Platform: Small Molecules Primary Need Targeted delivery to the retina with prolonged durability to enhance efficacy and relieve treatment burden

The Opportunity Pan-VEGF inhibition potentially more efficacious than current approaches Improve long-term, real-world visual outcomes for patients Reduce patient burden from monthly injections to every six months or longer Provide physicians with ability to titrate dose based on patient need Protect the anterior chamber from toxic exposure to TKIs Primary Need Durable maintenance of vision and reduced treatment burden in wet AMD patients TKIs = Tyrosine Kinase Inhibitors Axitinib for Suprachoroidal Injection (CLS-AX): A Potential Solution for Treatment Burden

INLYTA is a registered trademark of Pfizer, Inc. Items Details Target Patients For patients receiving frequent intravitreal anti-VEGF injections for neovascular AMD and diabetic macular edema Agent / Route of Administration Axitinib suspension for suprachoroidal injection Mechanism of Action Broadly inhibits VEGF angiogenesis as a tyrosine kinase inhibitor (TKI) of VEGF receptors VEGFR-1, VEGFR=2, VEGFR-3, c-KIT and PDGFR Regimen Twice yearly Historic development & regulatory history by Pfizer, Inc. INLYTA® (axitinib) tablets Approved for renal cell carcinoma from US FDA (2012), EMA (2012), UK MHRA (2012) and Australian TGA (2012) CLS-AX Overview

AMD Vascular Endothelial Growth Factor Treatment Approaches Anti-VEGF-A increases VEGF-C 1 & VEGF-D2 Broad VEGF blockade may improve outcomes A Phase 2 study yielded better AMD outcomes with anti-VEGF-A,C,D vs anti-VEGF-A Current AMD Therapies Predominantly Focus on VEGF-A Blockade, not VEGF Receptors Inhibits VEGFR-1, VEGFR-2, VEGFR-3 Inhibited corneal, retinal, and choroidal angiogenesis in animal models3-7 More effective than other TKIs for experimental corneal neovascularization in animal models Better ocular cell biocompatibility than other TKIs8 Suprachoroidal Axitinib May Improve Outcomes with Its Broad VEGF Blockade Sources: 1. Cabral T et al. Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers. Ophthalmol Retina. 2018 January ; 2(1): 31–37. doi:10.1016/j.oret.2017.04.004. | 2. Lieu et al. The Association of Alternate VEGF Ligands with Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer. PLoS ONE 8(10): e77117. | 3. Riquelme et al. Topical axitinib is a potent inhibitor of corneal neovascularization. Clinical and Experimental Ophthalmology 2018; 46: 1063–1074 | 4. Yuan et al. Ocular Drug Delivery Nanowafer with Enhanced Therapeutic Efficacy. ACS Nano. 2015 Feb 24;9(2):1749-58. | 5. Giddabasappa et al. Axitinib inhibits retinal and choroidal neovascularization in in-vitro and in-vivo models. Exp Eye Res. 2016, 145: 373-379. | 6. Nakano et al. Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal Rats. Exp Eye Res. 2016. 143: 120-131. | 7. Kang et al. Antiangiogenic Effects of Axitinib, an Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase, on Laser-Induced Choroidal Neovascularization in Mice. Curr Eye Res. 2012. 38: 119-127. | 8. Theile et al. Multikinase Inhibitors as a New Approach in Neovascular Age-Related Macular Degeneration (AMD) Treatment: In Vitro Safety Evaluations of Axitinib, Pazopanib and Sorafenib for Intraocular Use. Klin Monatsbl Augenheilkd 2013; 230: 247-254. | Image by Mikael Häggström, used with permission. Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.

CLS-AX May Address Unmet Needs in Neovascular AMD Sources: 1. Heier JS et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537-2548. | 2. Brown DM et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology. 2009;116:57-65.e5. | 3. Rosenfeld PJ et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431. | 4. Ciulla TA et al. Visual Acuity Outcomes and Anti-Vascular Endothelial Growth Factor Therapy Intensity in Neovascular Age-Related Macular Degeneration Patients: A Real-World Analysis of 49,485 Eyes. Ophthalmol Retina. 2019 May 25. pii: S2468-6530(19)30280-5. | 5. Rao P, Lum F, Wood K, et al. Real-world vision in age-related macular degeneration patients treated with single anti-VEGF drug type for 1 year in the IRIS Registry. Ophthalmology. 2018;125:522e528. | 6. Busbee BG et al. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013;120:1046-1056. | 7. Schmidt-Erfurth U et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121:193-201. Treatment Burden At 1 year, with on-label anti-VEGF dosing 1-3 : ~1/5 of patients lose BCVA ~1/2 do not achieve ≥ 20/40 ~2/3 do not gain ≥ 3 lines BCVA At 1 year, “real-world” patients improve by only 1-3 letters 4,5 Ceiling of Efficacy Increased anti-VEGF dosage or more intense regimens yield no additional BCVA benefit 1,6,7 Limited Outcomes At 1 year, “real-world” patients receive only 6-7 injections 4,5 Under-treatment contributes to poor real-world outcomes

Concentration (nM) CLS-AX: High Drug Levels Maintained in RPE-Choroid-Sclera High Retina Levels: Sufficient to block VEGF pathway Low Plasma Levels: <1 ng/mL Time (days) Source: Based on non-clinical data 2.4 mg Drug remaining (mg) Time (days) Half-life > 3 months >60% remaining at 3 months

Topical Axitinib More Effectively Inhibited Experimental Murine Corneal Neovascularization than Sunitinib and Sorafenib (same dose) Source: Yuan et al. Ocular Drug Delivery Nanowafer with Enhanced Therapeutic Efficacy. ACS Nano. 24 Feb 2015;9(2):1749-58

Potential to Disrupt the AMD Treatment Landscape Current Therapy Treatment burden Limited outcomes Ceiling of efficacy Focused VEGF Blockade Short Acting (1-3 months) CLS-AX Targeted for efficacy Compartmentalized for safety Biovailable with prolonged PK for durability Broad VEGF Blockade Long Acting ( > 6 months)

Opportunity Avoid risks of vitrectomy (surgery) Avoid risks of retinotomy, subretinal injection, and macular detachment Potential for broader retinal coverage Enhance patient access Convert gene therapy into an office-based procedure Broad Applicability of SCS Injection Platform: Ocular Gene Therapy Primary Need Targeted delivery of ocular gene therapies in safe, effective, repeatable, and non-surgical manner

DNA Nanoparticle Gene Therapy and the Suprachoroidal Space Potential advantages: Efficacy: demonstrated in numerous ocular animal models Transfer large genes (up to ~20 kb) Safety: Non-immunogenic, without viral capsid proteins or pre-existing immunity. Potential for repeat dosing Higher doses possible to enhance transfection Potential synergies with suprachoroidal injection: In office, repeat dosing as needed Targeted circumferential compartmentalized spread to large surface areas Potentially ideal distribution for inherited retinal disease treatment or biofactory approach Well established literature on DNA nanoparticle gene therapy Preclinical studies demonstrate SC injections of DNA nanoparticles (DNPs) may offer the potential for a safe and efficient delivery method

Preclinical SCS and Subretinal Injections of DNA Nanoparticles Produced Comparable Luciferase Activity Source: Szilárd Kiss, MD, Macula Society Presentation February 2019 CHOROID-RPE-Sclera Non-Viral Luciferase, Rabbit RETINA Non-Viral Luciferase, Rabbit DNA Nanoparticles Transfect Choroid and Retina

Source: Ding, K., Shen, J., Hafiz, Z., Hackett, S. F., Silva, R. L. E., Khan, M., ... Campochiaro, P. A. (2019). AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression. Journal of Clinical Investigation. doi: 10.1172/jci129085 Partnered Program: Viral Vectors Preclinical Activity SC RGX-314 resulted in similar expression of anti-VEGF Fab Suprachoroidal delivery of NAV AAV8-based gene therapy may avoid injected drug exposure to the vitreous and anterior segment of eye SC RGX-314 resulted in similar activity of anti-VEGF Fab with suppression of VEGF-induced vascular leakage as subretinal delivery

Core Advantages of Treating Via the Suprachoroidal Space Sources: PK = pharmacokinetic | 1. Rai UDJ, Young SA, Thrimawithana TR, et al. The suprachoroidal pathway: a new drug delivery route to the back of the eye. Drug Discov Today. 2015;20(4):491-495. 3. Moisseiev E, Loewenstein A, Yiu G. The suprachoroidal space: from potential space to a space with potential. Clin Ophthalmol. 2016;10:173-178. 2. Chiang B, Jung JH, Prausnitz MR. The suprachoroidal space as a route of administration to the posterior segment of the eye. Adv Drug Deliv Rev. 2018;126:58-66. TARGETED The back of the eye is the location of many irreversible and debilitating visual impairments1 BIOAVAILABLE PROLONGED PK Fluid spreads circumferentially and posteriorly when injected within the suprachoroidal space, bathing the choroid and adjacent areas with drug2 COMPARTMENTALIZED Drug is compartmentalized in the suprachoroidal space, which helps keep it away from non-diseased tissues2 for efficacy for safety for durability