Optilume
Instruction Manual for FDA models including: Optilume BPH Catheter System, BPH Catheter System, Catheter System
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DocumentDocumentInstructions for Use Caution: Federal law restricts this device to sale by or on the order of a physician. Page 1 of 30 1124-004 rA Draft Table of Contents 1 DEVICE DESCRIPTION ...................................................................................................................... 3 1.1 Optilume BPH Catheter System .................................................................................................. 3 1.2 Available Sizes and Nominal Paclitaxel Dose ............................................................................. 4 2 INDICATIONS FOR USE ..................................................................................................................... 4 3 CONTRAINDICATIONS....................................................................................................................... 4 4 WARNINGS.......................................................................................................................................... 4 5 PRECAUTIONS ................................................................................................................................... 5 6 DRUG INFORMATION......................................................................................................................... 6 6.1 Mechanism of Action ................................................................................................................... 6 6.2 Drug Interactions ......................................................................................................................... 6 6.3 Carcinogenicity, Genotoxicity, and Reproductive Toxicology...................................................... 6 6.4 Vascular Paclitaxel Coated Device Meta-Analysis ...................................................................... 7 7 HOW SUPPLIED.................................................................................................................................. 8 8 POTENTIAL ADVERSE EFFECTS ..................................................................................................... 8 9 STORAGE ............................................................................................................................................ 8 10 RECOMMENDED ITEMS .................................................................................................................... 8 11 DIRECTIONS FOR USE ...................................................................................................................... 8 11.1 Perioperative Medications ........................................................................................................... 8 11.2 Optilume BPH Size Selection ...................................................................................................... 9 11.3 Balloon Preparation ..................................................................................................................... 9 11.4 Pre-dilation................................................................................................................................. 10 11.5 Drug Coated Balloon Dilation .................................................................................................... 12 11.6 Post Procedure Care ................................................................................................................. 13 12 SUMMARY OF CLINICAL STUDIES ................................................................................................ 13 12.1 Primary Study ............................................................................................................................ 13 12.2 Supplemental Clinical Study ...................................................................................................... 28 13 WARRANTY....................................................................................................................................... 29 14 SYMBOLS USED IN THE DEVICE LABELS .................................................................................... 30 Page 2 of 30 1124-004 rA Draft 1 DEVICE DESCRIPTION 1.1 Optilume BPH Catheter System The Optilume BPH Catheter System is a combination drug/device minimally invasive surgical therapy (MIST) comprised of an uncoated pre-dilation balloon catheter and a separate drug coated balloon (DCB) catheter. The distal end of each catheter has a semi-compliant, inflatable, double lobe balloon that is used to dilate the prostate. The double-lobe DCB catheter is coated with a proprietary coating containing the active pharmaceutical agent paclitaxel. The drug coating covers the working length of the balloon body. Each Optilume BPH Catheter is a single inflation lumen balloon catheter that terminates in an atraumatic tip. The folded balloon has a 14.5Fr profile. The device is inserted through the outer sheath of a rigid cystoscope and then visualized procedurally in a side-by-side fashion with a cystoscope. The balloon has a double lobe design with a neck separating the two sections. The balloon neck is reinforced preventing diameter growth during the inflation process. The double lobe design allows the balloon neck to seat in the bladder neck during inflation and helps prevent migration of the balloon into the bladder. The distal lobe of the balloon inflates in the bladder and aids in anchoring the device, while the proximal lobe of the balloon is positioned in the prostatic urethra to dilate the prostate and create an anterior commissurotomy. Both the predilation and the drug coated balloon catheters are identical, the only difference being the DCB is coated with the drug paclitaxel as shown in Figure 2. Figure 1. Inflated Pre-dilation Balloon Catheter Figure 2. Inflated Drug Coated Balloon Catheter The Optilume BPH Catheter System is provided as a convenience kit, containing one predilation balloon catheter, one DCB catheter, and the accessories needed to complete a procedure. Catalogue numbers for the different kit configurations are provided in Table 1. Page 3 of 30 1124-004 rA Draft Table 1. Catalogue Number Identification of the Optilume BPH Kits Catalogue Number Description Pre-dilation DCB Catheter Size Catheter Size 1189-30030 Optilume BPH Prostatic Dilation Kit 30x30 90Fr x 30mm 90Fr x 30mm 1189-30035 Optilume BPH Prostatic Dilation Kit 30x35 90Fr x 30mm 90Fr x 35mm 1189-30040 Optilume BPH Prostatic Dilation Kit 30x40 90Fr x 30mm 90Fr x 40mm 1189-30045 Optilume BPH Prostatic Dilation Kit 30x45 90Fr x 30mm 90Fr x 45mm 1.2 Available Sizes and Nominal Paclitaxel Dose The Optilume BPH Catheter System is available with one pre-dilation balloon size (90Fr x 30mm) and four DCB sizes which are selected based on prostatic urethral length (Table 2). The drug coating covers the working length of the balloon component of the DCB and is evenly distributed across the balloon surface at a nominal paclitaxel dose density of 2.4 g/mm2. The drug coating is released from the balloon and transferred to the prostatic urothelium during balloon inflation. Table 2. DCB Sizes and Nominal Paclitaxel Dose Balloon Diameter Balloon Treatment Length (mm) 90Fr (30mm) 30 35 40 45 Paclitaxel Dose (g) 10,262 11,433 12,567 13,661 2 INDICATIONS FOR USE The Optilume BPH Catheter System is indicated for the treatment of obstructive urinary symptoms associated with Benign Prostatic Hyperplasia (BPH) in PHQ 50 years of age. 3 CONTRAINDICATIONS The Optilume BPH Catheter System is contraindicated for use in: x Patients with known hypersensitivity to paclitaxel or structurally related compounds x Patients with an active urinary tract infection x Patients with an artificial urinary sphincter x Patients with a penile prosthesis 4 WARNINGS x The Optilume BPH Catheter System should be used only by physicians who are experienced and knowledgeable with the clinical and technical aspects of transurethral endoscopic treatment of BPH. x Urotronic requires physician training on the Optilume BPH Catheter System prior to use. Please contact Urotronic for more information. x The Optilume BPH Catheter is supplied for single use only. Do not reprocess or resterilize. Reprocessing and re-sterilizing could increase the risk of patient infection and risk of compromised device performance. x Each balloon catheter is supplied sterile. Do not use the catheter if the sterile barrier is damaged or opened. x The foil pouch and the outer surface of the inner Tyvek pouch are non-sterile. The Page 4 of 30 1124-004 rA Draft contents of the inner Tyvek pouch are sterile. Use proper sterile technique to transfer the device from the inner Tyvek pouch to the sterile field. x Do not use after the "Use By" date on the package label. x Men should abstain from sex or use barrier contraception (wear a condom) for 30 days post treatment to avoid exposure of sexual partner to paclitaxel. Paclitaxel may still be present at low levels after 30 days. x The Optilume BPH DCB contains paclitaxel, a known genotoxic aneugen capable of causing chromosomal abnormalities in sperm. Paclitaxel is present in semen for an extended duration after treatment with Optilume BPH. The total duration of time that paclitaxel remains in the semen post-procedure varies, but some men have had trace amounts detected up to 1 year after treatment. The risks associated with paclitaxel in semen are unknown. For this reason, men with partners of child-bearing potential should use highly effective contraceptive (to avoid fathering children) for at least 12 months post-procedure. Urologists should engage in a discussion with prospective patients regarding this risk and their individual family planning situation, with consideration of longer duration contraceptive use or other precautions based on a shared decision making process. Paclitaxel was detectable (i.e., equal to or greater than lower limit of quantitation of 0.1 ng/mL) in semen in 4/5 (80.0%), 5/7 (71.4%), 4/10 (40.0%), and 1/3 (33.3%) of evaluable subjects at 1 month, 3 months, 6 months, and 12 months post-treatment, respectively. Maximum paclitaxel concentrations in semen were 8.9, 7.5, 1.8, and 0.16 ng/mL at 1 month, 3 months, 6 months, and 12 months post-treatment, respectively, while group mean (SD) paclitaxel concentrations in semen at those same timepoints were 2.3 (3.7), 1.3 (2.8), 0.29 (0.53), and 0.09 (0.06) ng/mL. Of the three subjects who had evaluable data at 12 months post-treatment, one had detectable paclitaxel concentration in semen (0.16 ng/mL). The risks associated with these paclitaxel concentrations in semen are unknown. The effect of treatment with the Optilume BPH DCB on sperm and spermatogenesis is also unknown. x Always inflate with a sterile liquid. Never inflate with air, carbon dioxide, or any other gas. x The balloon catheters should not be inflated in excess of the rated burst pressure (RBP). Inflation to pressures above RBP may cause the balloon to rupture. x During use, each balloon catheter of the Optilume BPH Catheter System should be manipulated under direct visualization via cystoscopy. x If resistance is encountered at any time during insertion or removal, do not force passage. Resistance may cause damage to device or urethra. Ensure the balloon is fully deflated and under negative pressure during withdrawal. x Monitor for signs of anaphylaxis or hypersensitivity to paclitaxel. 5 PRECAUTIONS x Carefully inspect the product prior to use. Do not use the catheter if it is damaged or if the size, shape, or condition is unsuitable for the intended procedure. x Do not immerse or wipe the Optilume BPH DCB with any fluid prior to use, as the integrity of the drug coating may be damaged or compromised. Replace the DCB if the Page 5 of 30 1124-004 rA Draft balloon has come into contact with fluids prior to use. x Use dry sterile gloves or dry gauze pads to handle the Optilume BPH DCB prior to use. Care should be taken to minimize contact with the drug coated portion of the device. x Never inflate the Optilume BPH DCB outside the body or prior to reaching the prostatic urethra as it may disrupt the coating integrity. x For proper drug delivery to the prostatic urethra, allow the drug coating on the balloon to hydrate while in the urethra for approximately 1 minute prior to inflation. Maintain inflation of the catheter for a minimum of 5 minutes. To optimize the anterior commissurotomy and drug delivery, longer inflation times > 5 minutes may be performed at the discretion of the operator. x If the balloon catheter has a failure prior to or during inflation, replace the balloon catheter and inflate per procedure. If failure of the Optilume BPH DCB is after inflation to rated burst pressure (RBP), do not repeat/replace with a second DCB. x Handle and dispose of the used device in accordance with accepted medical practice and applicable local regulations for biohazard waste. 6 DRUG INFORMATION 6.1 Mechanism of Action The coating of the Optilume BPH DCB contains paclitaxel, an anti-mitotic pharmaceutical agent that specifically binds to and stabilizes microtubules. Paclitaxel has been reported to inhibit smooth muscle cell and fibroblast proliferation and migration as well as secretion of extracellular matrix. The combination of these effects may result in the inhibition of prostatic tissue hyperplasia and re-fusion of the lateral lobes after achievement of the anterior commissurotomy. 6.2 Drug Interactions Formal drug interaction studies have not been conducted for the Optilume BPH DCB. The respective instructions for use for all drugs used in conjunction with the Optilume BPH DCB should be consulted for interactions with paclitaxel. Consideration should be given to the potential for systemic and local drug interactions in the prostate in a patient who is taking a drug with known interactions to paclitaxel or when deciding to initiate drug therapy in a patient who has been treated with the Optilume BPH Catheter System. The metabolism of paclitaxel is catalyzed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4, and it is a substrate of P-glycoprotein. Potential drug interactions may occur with any drug that affects these isoenzymes. In the absence of formal drug interaction studies, caution should be exercised when administering paclitaxel. 6.3 Carcinogenicity, Genotoxicity, and Reproductive Toxicology The Optilume BPH DCB contains paclitaxel, a known genotoxic aneugen capable of causing chromosomal abnormalities in sperm. Paclitaxel is present in semen for an extended duration after treatment with Optilume BPH. The total duration of time that paclitaxel remains in the semen post-procedure varies, but some men have trace amounts detected up to 1 year after treatment. The risks associated with paclitaxel in semen are unknown. For this reason, men with partners of child-bearing potential should use highly effective contraceptive (to avoid fathering children) for at least 12 months post-procedure. Urologists should engage in a discussion with prospective patients regarding this risk and their individual family planning situation, with consideration of longer duration contraceptive use or other precautions based on a shared decision making process. Page 6 of 30 1124-004 rA Draft Paclitaxel was detectable (i.e., equal to or greater than lower limit of quantitation of 0.1 ng/mL) in semen in 4/5 (80%), 5/7 (71.4%), 4/10 (40.0%), and 1/3 (33.3%) evaluable subjects at 1 month, 3 months, 6 months, and 12 months post-treatment, respectively. Maximum paclitaxel concentrations in semen were 8.9, 7.5, 1.8, and 0.16 ng/mL at 1 month, 3 months, 6 months, and 12 months post-treatment, respectively, while group mean (SD) paclitaxel concentrations in semen at those same timepoints were 2.3 (3.7), 1.3 (2.8), 0.29 (0.53), and 0.09 (0.06) ng/mL. Of the three subjects who had evaluable data at 12 months posttreatment, one had detectable paclitaxel concentration in semen (0.16 ng/mL). The risks associated with these paclitaxel concentrations in semen are unknown. The effect of treatment with the Optilume BPH DCB on sperm and spermatogenesis is also unknown. 6.4 Vascular Paclitaxel Coated Device Meta-Analysis A meta-analysis of randomized, controlled trials for the use of paclitaxel coated devices in treating patients with peripheral arterial disease (PAD) was published by Katsanos et. al in 2018.1 This analysis suggested the possibility of an increased risk of mortality resulting from the use of paclitaxel-coated vascular devices. This higher risk of death was observed at time points at least two years after treatment with the paclitaxel-containing devices. The presence and magnitude of the late mortality risk should be interpreted with caution because of multiple limitations in the available data, including wide confidence intervals due to a small sample size, pooling of studies of different paclitaxel-coated devices that were not intended to be combined, substantial amounts of missing study data, no clear evidence of a paclitaxel dose effect on mortality, and no identified pathophysiologic mechanism for the late deaths. In January 2021, Nordanstig and colleagues published interim results of a large, randomized national registry trial evaluating paclitaxel coated devices against uncoated control devices that showed no significant increase in mortality for paclitaxel coated devices through a median of 2.5 years follow-up.2 These results complement published outcomes from large national health insurance databases in the US and Germany showing no increase in mortality risk with the use of paclitaxel-coated devices. Longer term follow-up through 5 years is ongoing for these studies. Patients receiving the Optilume BPH Catheter System will be treated with a paclitaxel-coated balloon for a different condition (BPH) in a different part of the body (the prostate). Unlike the cardiovascular application, the drug is deposited on the urethra and not in the blood, although a small amount of drug can diffuse through the urethra into the blood. The mortality rate in the PINNACLE study evaluating the Optilume BPH Catheter System was 0.6 deaths per 100 patient follow-up years, which is no different than the expected rate of mortality for men in this age group. 1 Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7(24):e011245. 2 Nordanstig J, James S, Andersson M, Andersson M, Danielsson P, Gillgren P, et al. Mortality with paclitaxel-coated devices in peripheral artery disease. N Engl J Med. 2020;383(26):2538-46. Page 7 of 30 1124-004 rA Draft 7 HOW SUPPLIED The Optilume BPH Catheter System is supplied as a convenience kit containing: x One (1) Optilume BPH Prostatic Pre-dilation Catheter x One (1) Optilume BPH Prostatic Dilation Drug Coated Balloon Catheter x One (1) 60mL Inflation device with pressure gauge and 3-way stopcock x One (1) 3-way stopcock x Two (2) Tuohy-Borst adapters Each component in the Optilume BPH kit is supplied sterile and intended for single use only. Each Optilume BPH Catheter is sterilized by ethylene oxide. Each balloon catheter is in a double pouch packaging system (foil and Tyvek pouches) contained within a single unit box. 8 POTENTIAL ADVERSE EFFECTS Potential adverse effects after treatment with the Optilume BPH Catheter System are similar to standard cystoscopic procedures and mechanical dilation and include, but are not limited to fever, bleeding, pain, urinary tract infection, false route of the urethra, dysuria, difficult urination, frequency/urgency/irritative urinary symptoms, urinary retention and related symptoms, blood in urine (hematuria), urinary incontinence, urethrorrhagia, blood in semen (hematospermia), ejaculatory dysfunction, bladder perforation, urethral and/or bladder neck strictures, injury or perforation to the urethra, sphincter or prostatic capsule, and inflammation of genitourinary system (prostatitis, orchitis, balanitis). Although systemic effects from the paclitaxel coating are not anticipated, adverse effects observed during intravenous administration of paclitaxel for chemotherapy include, but are not limited to, allergic reaction, alopecia, anemia, gastrointestinal symptoms, hematological dyscrasia (including leucopenia, neutropenia, thrombocytopenia), hepatic enzyme changes, myalgia/arthralgia, myelosuppression, and peripheral neuropathy. Maximum systemic paclitaxel levels after treatment with the Optilume BPH DCB are more than 100 times lower than with IV administration of paclitaxel for chemotherapy. 9 STORAGE The Optilume BPH Catheter System should be stored at room temperature between 15°C and 30°C (59°F and 86°F) in a dry location in its original packaging. The device should be used prior to the "Use By" date on the package label. 10 RECOMMENDED ITEMS Prepare the following items using sterile technique: x Lubricious surgical gel to aid with device insertion x 60 mL inflation device with pressure gauge x Three-way stopcock x Tuohy-Borst adapter x Rigid cystoscope (minimum sheath size 19.5F) x Sterile saline 11 DIRECTIONS FOR USE 11.1 Perioperative Medications It is recommended that physicians follow guidelines for pre-procedure medications and preparation for a cystoscopic urethral procedure, including the administration of a pre-procedure Page 8 of 30 1124-004 rA Draft antibiotic as appropriate. If a urinary tract infection (UTI) is present at the time of treatment, the patient must be treated until the infection is cleared before the Optilume BPH procedure can take place. The prostate is a highly vascularized organ and the Optilume BPH procedure, like other transurethral procedures for the treatment of BPH, may cause bleeding within the prostatic urethra. Peri-operative management of anticoagulant and antiplatelet medications is at the discretion of the treating physician and should balance the patient risk of thromboembolic events against the risk of hemorrhagic events. 11.2 Optilume BPH Size Selection Selection of the appropriate kit for the Optilume BPH procedure is based on the measured prostatic urethral length (PUL) of the patient. Use of transrectal ultrasound (TRUS) to determine the PUL is recommended. The PUL measurement should be taken in the mid-sagittal plane as a direct line from the base of the bladder neck to the proximal edge of the external urethral sphincter. Note: If an intravesical prostatic protrusion (IPP) is present, the measurement should be from the base of the bladder neck, NOT the tip of the IPP. Figure 3. Mid-sagittal TRUS Image Showing PUL Measurement PUL Measurement Catalogue Number (DCB Size) Table 3: Optilume BPH DCB Size Selection PUL 32-37mm PUL 37-42mm PUL 42-47mm 1189-30030 (90Fr x 30mm) 1189-30035 (90Fr x 35mm) 1189-30040 (90Fr x 40mm) PUL >47mm 1189-30045 (90Fr x 45mm) 11.3 Balloon Preparation Before use, each balloon catheter in the Optilume BPH kit must be prepared for use by evacuating air from the balloon catheter. The balloon lumen of the catheter contains air and the air must be displaced to make certain that only liquid fills the balloon while the catheter is in the urethra. Do not remove the balloon protector sheath during catheter preparation. 1. Open the inflation device package, remove the 3-way stopcock, and attach it to the Tuohy-Borst adapter. 2. Connect the Tuohy-Borst valve to the proximal catheter shaft. Ensure that the catheter Page 9 of 30 1124-004 rA Draft shaft does not interfere with the 3-way stopcock operation. 3. Fill the inflation device half-way with sterile saline and attach it to the stopcock. Turn the stopcock so fluid can flow between the inflation device and the balloon catheter. 4. With the inflation device pointing downwards, draw back plunger to full volume of syringe (this creates maximum negative pressure and allows air to evacuate above the fluid level) and hold until no air bubbles can be seen coming out of the saline in the syringe. Repeat as needed to purge the air from the catheter. 5. With catheter preparation complete, disconnect the Tuohy-Borst valve from the catheter shaft. 6. Fill the inflation device with 50cc normal saline and purge air from the line. 11.4 Pre-dilation Pre-dilation of the prostatic urethra should be completed with the Optilume BPH Pre-dilation Catheter to initiate an anterior commissurotomy prior to treatment with the Optilume BPH DCB Catheter. 1. Prepare the Optilume BPH Pre-dilation Catheter for use per Section 11.3. 2. Assemble and advance the rigid cystoscope (minimum sheath size 19.5Fr) through the urethra and into the bladder. Remove the optics and bridge (if applicable) leaving an open pathway through the rigid sheath into the bladder. 3. Remove the balloon protector sheath from the Optilume BPH Pre-dilation Balloon. 4. Insert the balloon catheter through the rigid cystoscope sheath and into the bladder. 5. Slide the outer rigid cystoscope sheath out of the patient and over the balloon catheter shaft while maintaining the balloon catheter in position. 6. Reassemble the rigid cystoscope sheath with the bridge and optics. Note: A smaller cystoscope sheath (e.g., 18F) may be used to visualize the balloon during placement. 7. Attach the Tuohy-Borst adapter with inflation device to the proximal catheter shaft. 8. Insert the reassembled cystoscope transurethrally up to the external sphincter. The Optilume BPH Catheter is used side-by-side with a cystoscope. 9. Locate the external sphincter with the cystoscope and position the tip of the cystoscope so visualization of the external sphincter can be maintained throughout the procedure. 10. Adjust the position of the balloon by pushing/pulling the catheter shaft until the blue Page 10 of 30 1124-004 rA Draft positioning marker is visible at the distal edge of the external urethral sphincter (Figure 4). Figure 4. Positioning of the Balloon Within the Prostatic Urethra 11. With the balloon properly positioned, inflate slowly while maintaining traction to seat the balloon at the bladder neck and prevent proximal migration into the bladder. During inflation, monitor the location of the blue positioning marker with the cystoscope. If the marker migrates proximally into the external sphincter (e.g., is no longer visible) or the treatment balloon has slipped into the bladder, deflate, and reposition the balloon as above and repeat the dilation process. Warning: If migration of the balloon distally into the external sphincter (toward the user) is observed during inflation, immediately stop, and reposition. 12. Continue slow inflation until the anterior prostatic commissure is separated. Achievement of an anterior commissurotomy is typically accompanied by a sudden drop in pressure on the inflation device pressure gauge as resistance from the tissue is overcome. Note: Once the balloon is inflated, check for migration into the bladder by pressing the catheter shaft gently towards the bladder. If the catheter shaft moves freely, the balloon has likely migrated into the bladder. If migration is observed, deflate the balloon, reposition the catheter as above, and repeat the dilation process. Do not repeat this procedure more than 3 times. Warning: The balloon catheters should not be inflated to pressures above the rated burst pressure (RBP). Inflation in excess of RBP may cause the balloon to rupture. 13. After complete dilation, deflate the balloon and visually confirm the anterior commissurotomy by advancing the cystoscope into the prostatic urethra. Note: If difficulty is encountered visualizing commissurotomy, increase fluid flow/pressure to improve visibility. 14. Do not exceed 3 inflation cycles to rated burst pressure. If a commissurotomy is not achieved after 3 inflation cycles, deflate, and withdraw the Optilume BPH Pre-dilation Balloon per the steps below and proceed to dilation with the DCB. 15. After initiation of the commissurotomy is confirmed, remove the cystoscope. 16. Deflate the balloon by applying negative pressure with the inflation device to aspirate Page 11 of 30 1124-004 rA Draft liquid from the balloon. Once the inflation device is filled with fluid, detach from the stopcock, purge fluid into a reservoir, reattach to the catheter, and repeat the aspiration process to ensure complete aspiration of liquid from balloon. Warning: If resistance is encountered at any time during insertion or removal, do not force passage. Resistance may cause damage to the device or urethra. Ensure the balloon is fully deflated and under negative pressure during withdrawal. 17. When the balloon is completely deflated, maintain vacuum and gently pull on the catheter shaft to withdraw the catheter from the patient's body. 11.5 Drug Coated Balloon Dilation 1. Prepare the Optilume BPH DCB for use per Section 11.3. 2. Advance the rigid cystoscope through the urethra and into the bladder. Remove the optics and bridge (if applicable) leaving an open pathway through the rigid sheath into the bladder. 3. Remove the balloon protector sheath from the Optilume BPH DCB. 4. Insert the Optilume BPH DCB through the rigid cystoscope and into the bladder. 5. Slide the outer rigid cystoscope sheath out of the patient and over the balloon catheter shaft while maintaining the balloon catheter in position. 6. Reassemble the rigid cystoscope sheath with the bridge and optics. 7. Attach the Tuohy-Borst adapter with inflation device to the proximal catheter shaft of the Optilume BPH DCB. 8. Insert the reassembled cystoscope transurethrally up to the external sphincter. The Optilume BPH Catheter is used side-by-side with a rigid cystoscope. 9. Locate the external sphincter with the cystoscope and position the tip of the cystoscope so visualization of the external sphincter can be maintained through the procedure. 10. Adjust the position of the balloon by pushing/pulling the catheter shaft until the blue positioning marker is visible at the distal edge of the external urethral sphincter (Figure 4). This step should be completed in approximately 1 minute while the drug coating is hydrating, such that the balloon can be inflated after hydration is complete. 11. With the balloon properly positioned, inflate slowly while maintaining traction to seat the balloon at the bladder neck and prevent proximal migration into the bladder. During inflation, monitor the location of the blue positioning marker with the cystoscope. If the marker migrates proximally into the external urethral sphincter (e.g., is no longer visible) or the treatment balloon has slipped into the bladder, deflate and reposition the balloon as above and repeat the dilation process. Warning: If migration of the balloon distally into the external sphincter (toward the user) is observed during inflation, immediately stop and reposition. 12. With the balloon properly positioned, inflate the balloon using the inflation device. Maintain inflation for a minimum of 5 minutes to assure complete propagation of the anterior commissurotomy and appropriate drug delivery. To optimize the anterior commissurotomy and drug delivery, inflation times > 5 minutes may be utilized at the discretion of the operator. Warning: The balloon catheters should not be inflated to pressures above the rated burst pressure (RBP). Inflation in excess of RBP may cause the balloon to rupture. Page 12 of 30 1124-004 rA Draft 13. Once the balloon is inflated, check for migration into the bladder by pressing the catheter shaft gently towards the bladder. If the catheter shaft moves freely, the balloon has likely migrated into the bladder. If migration is observed, deflate the balloon, reposition the catheter as above, and repeat the dilation process. 14. After completion of the commissurotomy, remove the cystoscope. Note: Avoid visualizing the prostatic urethra with the cystoscope after dilation with the Optilume BPH DCB, as the irrigation fluid from the scope may disturb the drug coating delivered to the prostatic urethra. 15. Deflate the balloon by applying negative pressure with the inflation device to aspirate liquid from the balloon. Once the inflation device is filled with fluid, detach from the stopcock, purge fluid into a reservoir, reattach to the catheter, and repeat the aspiration process to ensure complete aspiration of liquid from the balloon. Warning: If resistance is encountered at any time during insertion or removal, do not force passage. Resistance may cause damage to device or urethra. Ensure the balloon is fully deflated and under negative pressure during withdrawal. 16. When the balloon is completely deflated, maintain vacuum and gently pull on the catheter shaft to withdraw the catheter from the patient's body. 11.6 Post Procedure Care 1. Upon completion of the dilation procedure, insert a Foley catheter and flush the bladder with sterile saline until the effluent returns clear. Note: If difficulty is encountered during placement of the Foley catheter, it is recommended to place a guidewire and advance a council tip Foley over the guidewire to aid in placement. Rigid catheter guides are not recommended. 2. It is recommended to place the Foley catheter on mild-to-moderate traction during the recovery period post-procedure to provide tamponade of any bleeding prostatic vessels. Note: Use of traction for approximately 30 minutes post-procedure with at least a 30cc Foley balloon was found to reduce the rate of hematuria complications during clinical trials. 3. The Foley catheter should remain in place for a minimum of 2 days to allow adequate healing and absorption of the drug into the prostatic adenoma. 12 SUMMARY OF CLINICAL STUDIES 12.1 Primary Study The PINNACLE study was a prospective, multicenter, double blind, 2:1 randomized controlled trial comparing the Optilume BPH Catheter System to a sham control procedure. In addition, a single arm of 15 non-randomized subjects were enrolled and treated with the Optilume BPH Catheter System to gather paclitaxel pharmacokinetic data. Subjects randomized to the Sham arm were allowed to cross over to receive the Optilume BPH Catheter System prior to the close of their 12-month visit window. Study enrollment began in January 2020 and was completed in September 2021. A total of 148 subjects were randomized in the study, 100 to the Optilume BPH arm and 48 to the Sham arm at 18 investigational sites. Treatment with the Optilume BPH Catheter System included use of the Optilume BPH Pre-dilation Balloon to initiate an anterior commissurotomy followed by dilation with the Optilume BPH DCB to further dilate and deliver drug to the prostatic urethra. Page 13 of 30 1124-004 rA Draft The sham procedure utilized rigid cystoscopy followed by insertion of a sheathed (21F) Optilume BPH Pre-dilation Balloon that was modified to prevent inflation. Follow-up was completed at Foley removal, 14 days, 30 days, 3 months, 6 months, and 12 months and will be performed annually through 5 years for subjects treated with the Optilume BPH Catheter System. 12.1.1 Subject Accountability At the time of database lock, of 477 patients enrolled in the PMA clinical study, 148 were randomized, and 14 included in the PK sub-study. Subject disposition and visit compliance for the randomized cohort through 12 months is summarized in Table 4 and Figure 5. Withdrawals prior to the 12-month visit included 10 subjects randomized to the Optilume BPH arm (2 withdrew prior to receiving the study treatment, 2 lost to follow-up, 2 withdrew consent, 2 underwent a BPH surgical procedure, 2 initiated BPH medications) and 2 subjects randomized to the Sham arm (2 initiated BPH medications). Twenty subjects in the Sham arm crossed over to receive Optilume BPH prior to the 12-month visit. Primary efficacy and secondary endpoint analyses were performed using the intent-to-treat (ITT) data set which included all randomized subjects. Safety analyses were performed using the as-treated (AT) data set based on the treatment received. The AT data set excludes two subjects who were randomized to the Optilume BPH arm but did not receive the study treatment. Table 4. Visit Compliance for Randomized Cohort Visit Compliance1 Study Visit Optilume BPH Sham (n=100) (n=48) Participants who received study treatment 98.0% (98/100) 100.0% (48/48) Participants who completed Foley Removal 100.0% (98/98) 100.0% (48/48) Participants who completed 14 Day visit 98.0% (96/98) 97.9% (47/48) Participants who completed 30 Day visit 99.0% (97/98) 100.0% (48/48) Participants who completed 3 Month visit 97.9% (94/96) 100.0% (48/48) Participants who completed 6 Month visit 97.9% (91/94) 97.2% (35/36) Participants who completed 12 Month visit 98.9% (89/90) 100.0% (26/26) 1Denominator represents the number of subjects eligible for a visit, while the numerator represents the number of visits completed. Subjects that are withdrawn from the study prior to the visit window opening are excluded from the denominator. Page 14 of 30 1124-004 rA Draft ¥ For the primary endpoint intent-to-treat (ITT) analysis, subjects receiving alternative BPH therapy were imputed as having no improvement, while endpoint status for subjects with missing data were imputed via multiple imputation. Figure 5. Subject Accountability Diagram for Randomized Cohort 12.1.2 Study Population Demographics and Baseline Parameters The demographics of the study population are typical for a BPH study performed in the US. Demographics, baseline genitourinary medical history, and baseline prostate characteristics were well matched between groups. Table 5. Demographics and Genitourinary Medical History Optilume BPH Sham Characteristic (N=100) (N=48) Demographics Age 64.5 ± 6.4 (98) 65.5 ± 5.6 (47) P-Value1 0.3769 Page 15 of 30 1124-004 rA Draft Characteristic Optilume BPH (N=100) Sham (N=48) P-Value1 Race American Indian or Alaska Native 0.0% (0/100) 0.0% (0/48) 0.1877 Asian 2.0% (2/100) 0.0% (0/48) Black or African American 3.0% (3/100) 10.4% (5/48) Hawaiian or Pacific Islander 0.0% (0/100) 0.0% (0/48) White 94.0% (94/100) 89.6% (43/48) Multi-Racial 1.0% (1/100) 0.0% (0/48) Ethnicity Hispanic or Latino 13.0% (13/100) 6.3% (3/48) 0.2157 Not Hispanic or Latino 87.0% (87/100) 93.8% (45/48) BMI 29.32 ± 4.45 (100) 29.06 ± 4.72 (48) 0.7420 Medical History Urinary Incontinence No 100.0% (100/100) 100.0% (48/48) N/A Yes 0.0% (0/100) 0.0% (0/48) LUTS Dysuria 16.0% (16/100) 16.7% (8/48) 0.9180 Frequency 91.0% (91/100) 100.0% (48/48) 0.0586 Hesitancy 73.0% (73/100) 79.2% (38/48) 0.4173 Incomplete Voiding 85.0% (85/100) 91.7% (44/48) 0.2564 Nocturia 91.0% (91/100) 95.8% (46/48) 0.3445 Poor Stream 89.0% (89/100) 91.7% (44/48) 0.7745 Terminal Dribbling 49.0% (49/100) 52.1% (25/48) 0.7254 Urgency 80.0% (80/100) 91.7% (44/48) 0.0715 Hematuria 6.0% (6/100) 2.1% (1/48) 0.4284 Retention 13.0% (13/100) 18.8% (9/48) 0.3573 Other Genitourinary History Kidney Stone 13.0% (13/100) 20.8% (10/48) 0.2182 Erectile Dysfunction 56.0% (56/100) 54.2% (26/48) 0.8336 Bladder Stone 3.0% (3/100) 0.0% (0/48) 0.5512 Urinary Tract Infection 6.0% (6/100) 4.2% (2/48) 0.7235 Bacterial Prostatitis 5.0% (5/100) 4.2% (2/48) 1.0000 Cystitis 2.0% (2/100) 0.0% (0/48) 0.5587 Other 34.0% (34/100) 29.2% (14/48) 0.5565 Prostate Specific Antigen (ng/mL) 2.42 ± 1.98 (100) 2.20 ± 1.82 (48) 0.5135 IPSS Score 23.4 ± 5.5 (100) 24.3 ± 5.8 (48) 0.3916 Qmax (mL/sec) 8.85 ± 2.17 (100) 8.95 ± 1.80 (48) 0.7888 Post-Void Residual Volume (mL) 84.1 ± 70.2 (99) 89.4 ± 73.9 (48) 0.6750 1Continuous variables tested with two-sample t-test and categorical variables tested with chi square test. When expected cell counts were < 5, then an Exact Chi-Square test was used. Page 16 of 30 1124-004 rA Draft Table 6. Baseline Prostate Characteristics Prostate Characteristics Optilume BPH (N=100) Sham (N=48) P-Value1 Prostate Width (mm) 48.90 ± 6.72 (100) 49.99 ± 5.05 (48) 0.2754 Prostate Height (mm) 37.07 ± 7.52 (100) 36.18 ± 7.14 (48) 0.4976 Prostate Length (mm) 46.62 ± 6.33 (100) 46.46 ± 5.39 (48) 0.8791 Prostate Volume (mL) 44.88 ± 14.53 (100) 45.00 ± 13.16 (48) 0.9633 Intravesical Prostatic Protrusion 28.0% (28/100) 33.3% (16/48) 0.5064 IPP Size (mm) 5.07 ± 2.19 (28) 5.31 ± 1.54 (15) 0.7059 1Continuous variables tested with two-sample t-test and categorical variables tested with chi-square test. 12.1.3 Efficacy Outcomes 12.1.3.1 Primary Efficacy Endpoint The primary efficacy endpoint was a comparison of the change in International Prostate Symptom Score (IPSS) at 3 months for the Control group and at 12 months for the Optilume BPH group. The endpoint incorporated a super-superiority margin of 25% for the sham effect at 3 months. The analysis was based on the ITT cohort which included 148 evaluable subjects (48 sham subjects at 3 months and 100 Optilume BPH subjects at 12 months). Subjects undergoing alternative therapy for ongoing/recurrent LUTS prior to the scheduled timepoint were imputed as having no change from baseline. Missing data were accounted for using multiple imputation. Incorporating the 25% super superiority margin, the imputed difference between arms was +1.4 (p=0.178). The improvement in IPSS for the Optilume BPH arm at 12 months did not reach statistical significance with a 25% super-superiority margin when compared to the improvement in the Sham arm at 3 months (Table 7). Table 7. Primary Efficacy Endpoint Improvement in IPSS (ITT, Multiple Imputation) Variable Sham (3 Months, N=48) Optilume BPH (12 Months, N=100) Difference [95%CI] Improvement in IPSS Mean [95%CI] Improvement in IPSS (w/ 25% Margin) Mean [95%CI] 8.0 [5.8, 10.3] 10.0 [7.5, 12.5] 11.5 [9.7, 13.2] 3.4 [0.6, 6.2] 1.4 [-1.6, 4.5] P-value is based on a two-sample, independent t-test. A post-hoc analysis was performed comparing the improvement in IPSS at 12 months for the Optilume BPH group to the improvement of a historical sham control at 3 months based on a systematic review of the literature of sham endoscopic procedures in randomized trials for BPH. A total of 8 studies were included in the analysis and used to generate the pooled sham effect (weighted average) across studies.3-10 Four studies reported a paired change in IPSS from baseline to 3 months. 5,6,8,9 Comparing the improvement in IPSS against the pooled sham effect from the literature as a performance goal shows a benefit for Optilume BPH both with and without a 25% super-superiority margin (Table 8). A similar outcome is seen when utilizing only 3 Albala DM, Fulmer BR, Turk TM, Koleski F, Andriole G, Davis BE, et al. J Endourol. 2002;16(1):57-61. 4 Barbalias GA, Liatsikos EN. Int J Urol. 1998;5(2):157-62. 5 Blute ML, Patterson DE, Segura JW, Tomera KM, Hellerstein DK. J Endourol. 1996;10(6):565-73. 6 Chughtai B, Elterman D, Shore N, Gittleman M, Motola J, Pike S, et al. Urology. 2021;153:270-6. 7 Larson TR, Blute ML, Bruskewitz RC, Mayer RD, Ugarte RR, Utz WJ. Urology. 1998;51(5):731-42. 8 McVary KT, Gange SN, Gittelman MC, Goldberg KA, Patel K, Shore ND, et al. J Urol. 2016;195(5):1529-38. 9 Roehrborn CG, Gange SN, Shore ND, Giddens JL, Bolton DM, Cowan BE, et al. J Urol. 2013;190(6):2161-7. 10 Roehrborn CG, Preminger G, Newhall P, Denstedt J, Razvi H, Chin LJ, et al. Urology. 1998;51(1):19-28. Page 17 of 30 1124-004 rA Draft those publications reporting paired change scores. Table 8. Comparison of Literature Sham Improvement in IPSS at 3 Months to Optilume BPH at 12 Months Literature Sham Optilume BPH Variable (3 Months) (12 Months) Composite Literature Outcomes 5.9 (n=401) Composite Literature Outcomes 7.4 (w/ 25% Super Superiority Margin) (n=401) 11.5 ± 7.8 Composite Literature Outcomes (paired) 5.6 ± 8.0 (n=94) (n=215) Composite Literature Outcomes 7.0 ± 10.0 (paired, w/ 25% Super Superiority Margin) (n=215) Optilume BPH mean improvement utilizing `Retreatments Imputed' methodology, where those receiving alternative treatment are imputed as having no improvement. 12.1.3.2 Secondary Endpoints Hypotheses for the secondary endpoints were not formally tested because the study failed to meet its primary effectiveness endpoint and supplemented by post-hoc analysis. Secondary Endpoint 1 Average IPSS Improvement in Test Arm at 12 Months The average percent improvement in IPSS from baseline to 12 months was compared against a performance goal of 30%. Subjects undergoing alternative therapy for ongoing/recurrent LUTS prior to the scheduled timepoint were considered as having no improvement, while subjects considered missing at random were imputed utilizing multiple imputation as per the primary efficacy endpoint analysis. The average improvement from baseline to 12 months for the Optilume BPH arm was 49%, which is greater than the target 30% threshold. Table 9. Secondary Endpoint 1 Average IPSS Improvement at 12 Months Optilume BPH Endpoint (n=100) % Improvement in IPSS Mean ± SE 49.1% ± 3.2% [95% CI] [42.7%, 55.4%] Secondary Endpoint 2 Responder Rate at 3 Months (Optilume BPH) vs 3 Months (Sham) The rate of responders at 3 months in the Optilume BPH arm was compared to the rate of responders at 3 months in the Sham arm. A responder is defined as a subject who has an IPSS LPSURYHPHQWRIDWWKHOLVWHGWLPHSRLQWFRPSDUHGWREDVHOLQH6XEMHFWVXQGHUJRLQJ alternative therapy for ongoing/recurrent LUTS prior to the scheduled timepoint were considered as having no improvement in the analysis. The responder rate at 3 months was numerically higher in the Optilume BPH arm compared to the Sham arm. Table 10. Secondary Endpoint 2 Responder Rate at 3 Months Endpoint Sham Optilume BPH Responder Rate (30%) Proportion (n/N) 52.1% (25/48) 68.8% (66/96) [95% CI] [37.2%, 66.7%] [58.5%, 77.8%] N=4 patients excluded from analysis due to missing values. Page 18 of 30 1124-004 rA Draft Secondary Endpoint 3 Responder Rate at 12 Months (Optilume BPH) vs 3 Months (Sham) The rate of responders at 12 months in the Optilume BPH arm was compared to the rate of responders at 3 months in the Sham arm. A responder is defined as a subject who has an IPSS LPSURYHPHQWRIDWWKHOLVWHGWLPHSRLQWFRPSDUHGWREDVHOLQH6XEMHFWVXQGHUJRLQJ alternative therapy for ongoing/recurrent LUTS prior to the scheduled timepoint were considered as having no improvement in the analysis. The responder rate at 12 months in the Optilume BPH arm was higher than the responder rate at 3 months in the Sham arm (76.6% vs 52.1%). Table 11. Secondary Endpoint 3 Responder Rate at 12 Months Sham Optilume BPH Endpoint (3 months) (12 months) Responder Rate (30%) Proportion (n/N) 52.1% (25/48) 76.6% (72/94) [95% CI] [37.2%, 66.7%] N=6 patients excluded from analysis due to missing values. [66.7%, 84.7%] Secondary Endpoint 4 Change in Qmax The change in Qmax at 12 months in the Optilume BPH arm was compared to the change in Qmax at 3 months in the Sham arm. Subjects opting to receive alternative therapy or withdrawing due to perceived lack of effectiveness were considered as having no improvement. The Optilume BPH arm showed a higher increase in Qmax at 12 months when compared to the increase in Qmax seen in the Sham arm at 3 months. Table 12. Secondary Endpoint 4 Change in Qmax from Baseline Variable Optilume BPH 12 Months (n=87) Sham 3 Months (n=43) Point Estimate of Difference [95%CI] Change in Qmax +9.7 ± 10.14 +5.5 ± 7.44 -4.2 (Mean ± SD, [95% CI]) [7.5, 11.8] [3.2, 7.8] [-7.6, -0.8] Uroflows with a voided volume <150mL were excluded from this analysis. 12.1.3.3 Ancillary Endpoints Analysis of the following ancillary endpoints demonstrated improvement through 12 months follow-up. Ancillary Endpoint 1 Additional Responder Analyses with a Responder Defined as IPSS Improvement of 35%, 40% and 50% The change in IPSS for both arms is presented using a Retreatments Imputed analysis which carries forward baseline values for subjects considered treatment failures (Table 9). The proportion of subjects with at least 35%, 40% and 50% improvement in IPSS is higher in the Optilume BPH arm compared to the Sham arm at all timepoints evaluated (Table 10). Page 19 of 30 1124-004 rA Draft Group Optilume BPH (N=100) n Mean ± SD Median Min, Max Sham (N=48) n Mean ± SD Median Min, Max Table 9. Change in IPSS Over Time (Retreatments Imputed) Baseline 14 Day 30 Day 3 Month 6 Month 100 23.4 ± 5.5 23.0 13, 34 87 15.7 ± 8.9 14.0 1, 35 97 13.4 ± 7.0 13.0 1, 35 96 13.0 ± 7.6 12.0 0, 32 94 12.8 ± 7.8 12.5 1, 33 48 24.3 ± 5.8 25.5 12, 34 47 15.1 ± 7.6 13.0 3, 33 48 15.0 ± 8.0 13.0 2, 33 48 16.2 ± 8.9 15.0 4, 34 47 18.1 ± 7.8 18.0 5, 32 12 Month 94 11.8 ± 7.6 10.0 0, 32 48 19.5 ± 9.2 21.0 4, 34 Table 10. Responder Rate Based on IPSS Improvement of 35%, 40% and 50% Improvement of percentage in IPSS (%) Visit Optilume BPH Sham Optilume BPH Sham Optilume BPH Sham 30 Day % (n/N) 95% CI1 63.9% (62/97) 54.2% (26/48) 59.8% (58/97) 52.1% (25/48) 43.3% (42/97) 37.5% (18/48) 53.5%, 73.4% 39.2%, 68.6% 49.3%, 69.6% 37.2%, 66.7% 33.3%, 53.7% 24.0%, 52.6% 3 Month % (n/N) 95% CI1 66.7% (64/96) 50.0% (24/48) 61.5% (59/96) 45.8% (22/48) 47.9% (46/96) 39.6% (19/48) 56.3%, 76.0% 35.2%, 64.8% 51.0%, 71.2% 31.4%, 60.8% 37.6%, 58.4% 25.8%, 54.7% 6 Month % (n/N) 95% CI1 68.1% (64/94) 36.2% (17/47) 60.6% (57/94) 31.9% (15/47) 45.7% (43/94) 25.5% (12/47) 57.7%, 77.3% 22.7%, 51.5% 50.0%, 70.6% 19.1%, 47.1% 35.4%, 56.3% 13.9%, 40.3% 12 Month % (n/N) 95% CI1 71.3% (67/94) 31.3% (15/48) 69.1% (65/94) 27.1% (13/48) 59.6% (56/94) 22.9% (11/48) 61.0%, 80.1% 18.7%, 46.3% 58.8%, 78.3% 15.3%, 41.8% 49.0%, 69.6% 12.0%, 37.3% Note: Timepoints after study exit due to treatment failure or crossover to treatment are imputed as failures 1Confidence intervals (CI) are estimated using the Clopper-Pearson (exact) approach. Ancillary Endpoints 2 and 8 Change in Post-void Residual (PVR) Urine Volume and Peak Flow Rate (Qmax) Table 11. Change in Qmax and PVR Over Time (Retreatments Imputed) Measure Group Baseline 30 Day 3 Month 6 Month 12 Month QMax (mL/sec) Optilume BPH (N=100) n Mean ± SD Median Min, Max 98 8.9 ± 2.2 8.9 5, 12 79 17.6 ± 9.0 16.8 4, 49 81 18.6 ± 9.7 17.2 4, 66 86 16.9 ± 8.9 14.7 5, 59 87 18.5 ± 10.2 17.0 5, 60 Sham (N=48) n Mean ± SD Median Min, Max 48 8.9 ± 1.8 9.0 6, 12 43 13.2 ± 6.3 11.5 5, 32 43 14.5 ± 7.8 13.0 5, 42 43 13.2 ± 6.8 10.9 6, 38 48 12.1 ± 6.5 10.0 6, 38 Page 20 of 30 1124-004 rA Draft Measure Group Baseline 30 Day 3 Month PVR (mL) Optilume BPH (N=100) n Mean ± SD Median Min, Max 99 84.1 ± 70.2 69.0 0, 298 92 60.5 ± 54.4 47.5 0, 248 91 69.5 ± 68.6 55.0 0, 435 Sham (N=48) n Mean ± SD Median Min, Max 48 89.4 ± 73.9 66.0 0, 284 46 91.8 ± 81.6 76.5 0, 348 48 98.4 ± 102.4 57.0 0, 385 Voided volumes < 150 mL are excluded from the Qmax analysis. 6 Month 90 61.4 ± 58.8 45.0 0, 313 47 96.9 ± 103.8 56.0 10, 534 12 Month 90 59.5 ± 52.6 42.5 0, 202 47 93.4 ± 98.0 69.0 0, 500 Ancillary Endpoint 3 Change in Sexual Function (International Index of Erectile Function (IIEF), Male Sexual Health Questionnaire - Ejaculatory Dysfunction (MSHQ-EjD)) Measure Erectile Function Intercourse Satisfaction Orgasmic Function Table 12. IIEF Over Time (As Observed) Group Baseline 3 Month 6 Month Optilume BPH (N=98) n Mean ± SD Median Min, Max 97 15.6 ± 10.3 15.0 1, 30 92 16.5 ± 10.8 16.5 1, 30 91 17.3 ± 11.0 19.0 1, 30 Sham (N=48) n Mean ± SD Median Min, Max 48 16.8 ± 9.3 19.0 1, 30 47 17.6 ± 9.8 18.0 1, 30 35 19.8 ± 8.7 22.0 1, 30 Optilume BPH (N=98) n Mean ± SD Median Min, Max 98 5.7 ± 5.0 7.0 0, 15 92 5.8 ± 5.2 7.0 0, 14 91 6.5 ± 5.4 8.0 0, 15 Sham (N=48) n Mean ± SD Median Min, Max 48 6.3 ± 4.9 8.0 0, 15 47 6.9 ± 5.0 7.0 0, 15 35 7.5 ± 4.5 9.0 0, 13 Optilume BPH (N=98) n Mean ± SD Median Min, Max 98 5.8 ± 3.8 6.5 0, 10 92 5.6 ± 3.9 6.0 0, 10 91 6.7 ± 3.9 8.0 0, 10 Sham (N=48) n Mean ± SD Median Min, Max 48 6.1 ± 3.5 6.5 0, 10 47 6.3 ± 3.5 7.0 0, 10 35 6.6 ± 2.9 6.0 0, 10 12 Month 87 17.1 ± 11.1 16.0 1, 30 26 20.1 ± 8.4 22.5 4, 30 88 6.4 ± 5.4 8.0 0, 15 26 8.3 ± 4.4 9.5 0, 14 88 6.3 ± 3.8 8.0 0, 10 26 7.3 ± 2.9 8.0 0, 10 Page 21 of 30 1124-004 rA Draft Measure Group Baseline Sexual Desire Optilume BPH (N=98) n Mean ± SD Median Min, Max 97 6.3 ± 2.2 6.0 2, 10 Sham (N=48) n Mean ± SD Median Min, Max 48 6.4 ± 1.9 7.0 2, 10 Overall Satisfaction Optilume BPH (N=98) n Mean ± SD Median Min, Max 96 5.6 ± 2.7 6.0 2, 10 Sham (N=48) n Mean ± SD Median Min, Max 47 5.4 ± 2.7 5.0 2, 10 Note: A higher score indicates higher sexual function. 3 Month 92 6.5 ± 2.1 7.0 2, 10 47 6.1 ± 1.8 6.0 2, 9 92 6.2 ± 2.8 6.0 2, 10 45 5.9 ± 2.8 6.0 2, 10 6 Month 91 6.6 ± 2.2 7.0 2, 10 35 6.3 ± 1.7 6.0 3, 10 91 6.3 ± 2.9 6.0 2, 10 35 6.4 ± 2.8 6.0 2, 10 Table 13. MSHQ-EjD Over Time (As Observed) Measure Group Baseline 3 Month 6 Month Ejaculatory Function1 Optilume BPH (N=98) n Mean ± SD Median Min, Max 98 7.5 ± 3.9 7.0 1, 15 86 8.5 ± 4.8 9.0 1, 15 87 8.3 ± 4.5 9.0 1, 15 Sham (N=48) n Mean ± SD Median Min, Max 47 8.0 ± 3.4 8.0 1, 15 47 8.8 ± 3.9 9.0 1, 15 35 9.1 ± 3.4 10.0 1, 15 Ejaculation Bother2 Optilume BPH (N=98) n Mean ± SD Median Min, Max 98 2.5 ± 1.7 3.0 0, 5 86 1.9 ± 1.6 2.0 0, 5 87 2.1 ± 1.7 2.0 0, 5 Sham (N=48) n Mean ± SD Median Min, Max 47 2.2 ± 1.7 2.0 0, 5 47 2.0 ± 1.5 2.0 0, 5 35 2.1 ± 1.6 2.0 0, 5 1Higher score = Less ejaculation dysfunction (Possible Range 1 - 15) 2Higher score = Greater bother with ejaculation difficulties (Possible Range 0 - 5) 12 Month 89 6.5 ± 2.2 7.0 2, 10 26 6.4 ± 2.0 6.5 2, 10 86 6.3 ± 2.9 6.0 2, 10 26 6.5 ± 2.8 6.5 2, 10 12 Month 87 8.4 ± 4.6 9.0 1, 15 26 9.9 ± 3.5 10.0 4, 15 87 2.0 ± 1.7 2.0 0, 5 26 2.0 ± 1.8 1.5 0, 5 Page 22 of 30 1124-004 rA Draft Ancillary Endpoint 4 Change in BPH Impact Index (BPH-II) Table 14. BPH Impact Index Over Time (As Observed) Group Baseline 30 Day 3 Month 6 Month Optilume BPH (N=98) n Mean ± SD Median Min, Max 98 7.0 ± 2.9 7.0 1, 12 96 5.3 ± 3.2 5.0 0, 13 93 4.5 ± 3.2 4.0 0, 12 91 2.9 ± 2.8 2.0 0, 12 Sham (N=48) n Mean ± SD Median Min, Max 48 7.0 ± 3.0 7.0 0, 12 48 3.8 ± 3.1 3.0 0, 13 48 3.9 ± 3.5 3.0 0, 12 35 3.6 ± 2.7 4.0 0, 9 Ancillary Endpoint 5 Change in Quality of Life (EQ-5D) 12 Month 89 2.3 ± 2.5 2.0 0, 11 26 3.4 ± 3.1 3.0 0, 12 Table 15. EQ-5D Composite Over Time (As Observed) Measure Baseline 30 Day 3 Month 6 Month Optilume BPH (N=98) n Mean ± SD Median Min, Max 98 0.865 ± 0.123 0.861 0.49, 1.00 96 0.866 ± 0.116 0.861 0.39, 1.00 93 0.875 ± 0.120 0.861 0.38, 1.00 90 0.888 ± 0.132 0.876 0.46, 1.00 Sham (N=48) n Mean ± SD Median Min, Max 48 0.854 ± 0.108 0.854 0.51, 1.00 47 0.900 ± 0.106 0.876 0.49, 1.00 47 0.893 ± 0.101 0.876 0.62, 1.00 35 0.886 ± 0.096 0.861 0.72, 1.00 12 Month 88 0.878 ± 0.132 0.876 0.46, 1.00 26 0.887 ± 0.099 0.861 0.72, 1.00 Measure Optilume BPH (N=98) n Mean ± SD Median Min, Max Sham (N=48) n Mean ± SD Median Min, Max Table 16. EQ-5D VAS Over Time (As Observed) Baseline 30 Day 3 Month 6 Month 98 81.6 ± 14.4 85.0 25, 100 96 82.6 ± 13.9 87.5 40, 100 93 85.8 ± 11.4 90.0 40, 100 90 84.6 ± 14.0 89.0 10, 100 48 78.9 ± 13.7 80.0 30, 100 47 83.5 ± 11.0 85.0 50, 100 47 83.1 ± 10.4 85.0 50, 100 35 82.8 ± 7.9 85.0 70, 95 12 Month 88 86.5 ± 10.0 89.0 45, 100 26 84.3 ± 8.9 85.0 57, 100 Page 23 of 30 1124-004 rA Draft Ancillary Endpoint 6 Change in Pain Score Table 17. Peri-operative VAS Pain Scores (As Observed) Group Baseline Procedure Foley Removal 14 Day 30 Day Optilume BPH (N=98) n Mean ± SD Median Min, Max 98 1.2 ± 2.0 0.0 0, 8 97 4.1 ± 2.3 4.0 0, 10 96 2.4 ± 2.2 2.0 0, 10 95 1.6 ± 1.9 1.0 0, 9 97 1.4 ± 1.8 1.0 0, 8 Sham (N=48) n Mean ± SD Median Min, Max 48 1.3 ± 2.0 0.0 0, 7 48 2.6 ± 1.9 3.0 0, 7 48 2.8 ± 2.5 2.0 0, 8 47 0.9 ± 1.6 0.0 0, 8 48 0.6 ± 1.3 0.0 0, 6 3 Month 94 1.1 ± 1.6 0.0 0, 6 48 0.9 ± 1.6 0.0 0, 8 Ancillary Endpoint 7 Procedure Parameters Procedures were performed in an ambulatory surgical center (81.5%) or office-based location (18.5%). The average (SD) time for the Optilume BPH procedure from cystoscope insertion to removal of the treatment device was 26.0 (8.2) minutes (n=98). Ancillary Endpoint 9 Proportion of Subjects Experiencing a Return to `Normal' Symptom Severity (IPSS<8) Approximately one-third of subjects (30.9%, 29/94) treated with the Optilume BPH Catheter System returned to `normal' symptom levels by 12 months post-treatment compared to 14.6% (7/48) in the Control group. Table 18. Proportion of Subjects with IPSS<8 Visit Proportion of Subjects with IPSS <8 Optilume BPH Sham 3 Month % (n/N) 95% CI1 25.0% (24/96) 16.7%, 34.9% 20.8% (10/48) 10.5%, 35.0% 6 Month % (n/N) 95% CI1 29.8% (28/94) 20.8%, 40.1% 8.5% (4/47) 2.4%, 20.4% 12 Month % (n/N) 95% CI1 30.9% (29/94) 21.7%, 41.2% 14.6% (7/48) 6.1%, 27.8% Note: Timepoints after study exit due to treatment failure or crossover to treatment are imputed as failures 1Confidence intervals (CI) are estimated using the Clopper-Pearson (exact) approach. 12.1.4 Safety Outcomes The primary safety endpoint of the PINNACLE study was defined as the proportion of subjects experiencing a composite of major device-related serious complications through 12 months post-procedure: rectal or gastrointestinal fistula, fistula between the rectum and urethra, new onset severe urinary retention lasting >14 consecutive days post-healing, unresolved de novo stress urinary incontinence by 90 days, bleeding requiring transfusion, and urethra or prostatic capsule rupture requiring surgical intervention. No subjects experienced an event qualifying for the pre-defined composite of serious device-related complications through 12 months as adjudicated by the Clinical Events Committee (CEC). Page 24 of 30 1124-004 rA Draft Table 14. Primary Safety Endpoint Freedom from Major Device Related Complications Endpoint Sham (n=48) Optilume BPH (n=100) Difference (95% CI) Major device-related complications at 12 months 0.0% (0/48) 0.0% (0/100) 0.0% (0.0%, 0.0%) Adverse event summaries are based on the As-Treated cohort which included 98 subjects in the Optilume BPH arm treated with the device (Table 19). A summary of events adjudicated by the CEC as related to the study device or procedure is shown in Table 20. Table 19. Summary of Adverse Events by Arm (As Treated) Optilume BPH (N=98) Sham (N=48) Event Types Participant % Participant % Events (n/N) Events (n/N) Adverse Events 241 82.7% (81/98) 58 62.5% (30/48) Serious Adverse Events 15 14.3% (14/98) 3 6.3% (3/48) Treatment Related Adverse Events 143 71.4% (70/98) 15 25.0% (12/48) Device Related AE 121 67.3% (66/98) 11 16.7% (8/48) Procedure Related AE 22 18.4% (18/98) 4 8.3% (4/48) Treatment Related Serious Adverse Events 6 6.1% (6/98) 0 0.0% (0/48) Device Related SAE 5 5.1% (5/98) 0 0.0% (0/48) Procedure Related SAE 1 1.0% (1/98) 0 0.0% (0/48) Treatment-related serious adverse events were reported in 6 (6.1%) subjects, most commonly post-procedure hematuria (4 events) which resolved without sequelae. The most frequently reported treatment-related adverse events included hematuria (39.8%), urinary tract infection (11.2%), dysuria (8.2%), and mild stress urinary incontinence (7.1%). Treatment-related adverse events were mostly mild or moderate in severity (138/143, 97%). There were no life threatening (Grade 4) or fatal (Grade 5) events related to either the study device or procedure. A total of 41 hematuria and post-procedural hematuria events occurred in 39 subjects (39.8%) with most events being mild or moderate in severity (37/41, 90.2%) with a median time to resolution of 34 days. The rate and severity of hematuria events was decreased after implementation of post-operative care guidelines as described in section 11.6. Table 20. Device/Procedure Related Adverse Events (As Treated) Optilume BPH (N=98) Sham (N=48) System Organ Class/ CTC Term Grade 1-2 Participant Events % (n/N) Grade 3 Grade 1-2 Grade 3 Participant Participant Participant Events % (n/N) Events % (n/N) Events % (n/N) Gastrointestinal Disorders 0 0.0% (0/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) Abdominal pain 0 0.0% (0/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) General Disorders And 0 0.0% (0/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) Administration Site Conditions Fever 0 0.0% (0/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) Infections And Infestations 12 11.2% (11/98) 0 0.0% (0/98) 4 6.3% (3/48) 0 0.0% (0/48) Bladder infection 0 0.0% (0/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) Urinary tract infection 12 11.2% (11/98) 0 0.0% (0/98) 3 4.2% (2/48) 0 0.0% (0/48) Page 25 of 30 1124-004 rA Draft System Organ Class/ CTC Term Injury, Poisoning And Procedural Complications Investigations Elevated prostate specific antigen [PSA] Musculoskeletal And Connective Tissue Disorders Groin pain Low back pain Product Issues Catheter blockage Renal And Urinary Disorders Bladder cancer Bladder perforation Bladder spasm Dysuria Frequency of micturition Hematuria Leukocyturia Lower urinary tract symptoms Meatal stenosis Nocturia Overactive bladder Post micturition dribble Post procedural hematuria Stress urinary incontinence Urethral false passage Urethral pain Urethral stricture Urethritis Urinary incontinence (Urge/Mixed) Urinary retention Urinary urgency Voiding difficulty Reproductive System And Breast Disorders Anejaculation Ejaculation decreased Epididymitis Hematospermia Painful ejaculation Painful orgasm Pelvic pain Penile pain Perineal pain Prostatitis Retrograde ejaculation Optilume BPH (N=98) Sham (N=48) Grade 1-2 Grade 3 Grade 1-2 Grade 3 Participant Participant Participant Participant Events % (n/N) Events % (n/N) Events % (n/N) Events % (n/N) 0 0.0% (0/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 2 2.0% (2/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 2 2.0% (2/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 2 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 99 65.3% (64/98) 5 5.1% (5/98) 7 12.5% (6/48) 0 0.0% (0/48) 0 0.0% (0/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 0 0.0% (0/98) 1 1.0% (1/98) 0 0.0% (0/48) 0 0.0% (0/48) 6 6.1% (6/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 8 8.2% (8/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 3 3.1% (3/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 11 10.2% (10/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 5 4.1% (4/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 3 3.1% (3/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 2 2.0% (2/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 26 25.5% (25/98) 4 4.1% (4/98) 0 0.0% (0/48) 0 0.0% (0/48) 7 7.1% (7/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 2 2.0% (2/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 4 4.1% (4/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 5 5.1% (5/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 3 3.1% (3/98) 0 0.0% (0/98) 0 6 6.1% (6/98) 0 0.0% (0/98) 0 3 2.0% (2/98) 0 0.0% (0/98) 0 21 15.3% (15/98) 0 0.0% (0/98) 2 0.0% (0/48) 0.0% (0/48) 0.0% (0/48) 4.2% (2/48) 0 0.0% (0/48) 0 0.0% (0/48) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 0 0.0% (0/98) 0 0.0% (0/98) 1 2.1% (1/48) 0 0.0% (0/48) 4 4.1% (4/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 6 5.1% (5/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 3 3.1% (3/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 2 2.0% (2/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) Page 26 of 30 1124-004 rA Draft System Organ Class/ CTC Term Respiratory, Thoracic And Mediastinal Disorders Aspiration pneumonia Optilume BPH (N=98) Sham (N=48) Grade 1-2 Grade 3 Grade 1-2 Grade 3 Participant Participant Participant Participant Events % (n/N) Events % (n/N) Events % (n/N) Events % (n/N) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 1 1.0% (1/98) 0 0.0% (0/98) 0 0.0% (0/48) 0 0.0% (0/48) 12.1.5 Pharmacokinetic Profile A sub-study including 15 non-randomized subjects was conducted to determine the pharmacokinetic profile of paclitaxel in blood (plasma), urine, and semen after treatment with the Optilume BPH DCB. Determination of plasma paclitaxel concentration was evaluated immediately after completion of the procedure, at 1, 3, and 5 hours, and at Foley removal, 30 days, 3 months, and 6 months post-procedure. Urine paclitaxel concentration was evaluated immediately post-procedure, at Foley removal, and at 30 days, 3 months, and 6 months. Semen paclitaxel concentration was evaluated at 30 days, 3 months, and 6 months post-procedure. A summary of pharmacokinetic parameters, including maximum concentration (Cmax) and time to maximum concentration (Tmax) for plasma is in Table 21. Paclitaxel concentration over time in urine and semen can be found in Table 22 and Table 23, respectively. On average, paclitaxel concentration in plasma fell below the limit of quantitation of the method (0.10 ng/mL or 0.1 part per billion) by the time of Foley removal, while average paclitaxel concentration in urine approached the limit of quantitation by 6 months. Analysis of paclitaxel concentration in semen showed low but persistent levels of paclitaxel in semen through 6 months post-treatment. Of the three subjects who had evaluable data at 12 months post-treatment, one had detectable paclitaxel concentration in semen (0.16 ng/mL). Table 21. Summary of Plasma Pharmacokinetic Parameters Parameter Plasma Cmax (ng/mL) n Mean Min, Max Tmax (hr) n Median Min, Max 15 0.40 ± 0.54 <0.10, 2.24 15 1.0 ± 1.71 0.25, 5 Measure Mean ± SD Median Max, Min Subjects with Measurable Amt Table 22. Urine Paclitaxel Concentration Over Time Urine Paclitaxel Concentration (ng/mL) Baseline <0.1 ± 0.0 0hr 1,892.8 ± 4,530.6 Foley Removal 134.6 ± 221.9 30 Days 1.3 ± 1.5 3 Months 0.4 ± 0.7 <0.1 536.5 65.1 0.7 0.2 <0.1 17,500, 64.4 841, 3.6 5.5, <0.1 2.8, <0.1 0/13 (0.0%) 14/14 (100.0%) 13/13 (100.0%) 12/14 (85.7%) 9/14 (64.3%) 6 Months 0.1 ± 0.2 <0.1 0.6, <0.1 3/15 (20.0%) Page 27 of 30 1124-004 rA Draft Table 23. Semen Paclitaxel Concentration Over Time Measure Baseline Semen Concentration (ng/mL) 30 Days 3 Months 6 Months 12 Months Mean ± SD <0.10 ± 0.0 2.34 ± 3.69 1.30 ± 2.76 0.29 ± 0.53 0.09 ± 0.06 Median <0.10 0.86 0.27 <0.10 <0.10 Max, Min <0.10 8.89, <0.10 7.54, <0.10 1.75, <0.10 0.16, <0.10 Subjects with 0/6 4/5 5/7 4/10 1/3 Measurable Amt (0.0%) (80.0%) (71.4%) (40.0%) (33.3%) Only subjects with confirmed or suspected paclitaxel present in their semen at 6 months were required to provide 12-month semen samples. 12.2 Supplemental Clinical Study EVEREST-I was a prospective, non-randomized, open label, multicenter study to evaluate the safety and efficacy of the Optilume BPH Catheter system for the treatment of LUTS secondary WR%3+(OLJLEOHVXEMHFWVZHUHPHQ!\HDUVRIDJHZLWK/876VHFRQGDU\WR%3+,366 peak urinary flow rate 5-15 mL/sec, post-YRLGUHVLGXDOP/SURVWDWHYROXPH-80 grams, and prostatic urethral length 35-55 mm. Key exclusions included prior minimally invasive or surgical intervention of the prostate, intravesical prostatic protrusion >1 cm, and confounding urologic conditions (e.g., neurogenic bladder, stricture). Subjects had to undergo drug washouts prior to treatment including alpha blockers for 3 weeks and 5-alpha reductase inhibitors for 6 months. Subjects were followed at Foley removal, 2 weeks, 30 days, 3 months, 6 months, and 1-year post-treatment, and annually thereafter through 3 years. Follow-up is planned through 5 years. A total of 80 subjects were enrolled and treated at 6 clinical sites in Panama and the Dominican Republic. Subjects were 65 years old on average with a prostate volume of 35.9 grams. The primary efficacy endpoint was the responder rate at 3 months based on an improvement in ,366IURPEDVHOLQHZLWKRXWUHTXLULQJDGGLWLRQDOWKHUDS\$WPRQWKV were considered responders with a lower 90% confidence limit of 72.6% which met the performance goal of 50%. Measure IPSS n Mean ± SD IPSS QoL n Mean ± SD Qmax (mL/sec) n Mean ± SD PVR (mL) n Mean ± SD Table 24. EVEREST-I Results Summary Baseline 3 months 6 months 1 year 2 years 80 22.3 ± 4.9 79 8.1 ± 6.1 77 8.0 ± 7.2 75 7.9 ± 7.6 68 8.2 ± 7.3 80 4.6 ± 0.86 79 1.5 ± 1.33 77 1.6 ± 1.62 75 1.3 ± 1.38 68 1.6 ± 1.58 80 77 74 74 56 10.9 ± 2.92 20.5 ± 9.54 19.6 ± 8.67 18.4 ± 8.21 17.2 ± 8.98 80 77 74 74 56 63.1 ± 55.01 34.3 ± 33.08 28.8 ± 29.53 34.4 ± 35.25 45.0 ± 50.94 3 years 63 9.8 ± 8.0 63 1.8 ± 1.74 58 16.7 ± 10.63 58 49.1 ± 79.29 The primary safety endpoint was a composite of device and procedure related serious complications at 3 months including new onset severe urinary retention lasting >14 consecutive days post-healing, unresolved new onset stress urinary incontinence by 90 days, and bleeding requiring transfusion. Two subjects experienced stress urinary incontinence meeting the Page 28 of 30 1124-004 rA Draft endpoint criteria for a rate of 2.5%. Both subjects were treated with a larger diameter balloon that is no longer included in the matrix of available device sizes. 13 WARRANTY Urotronic warrants that reasonable care has been used in the design and manufacture of this product. This warranty is in lieu of and excludes all other warranties not expressly set forth herein, whether express or implied by operation of law or otherwise, including, but not limited to, any implied warranties for a particular purpose. Handling, storage, cleaning, and sterilization of this device as well as other factors relating to the patient, diagnosis, treatment, surgical procedures and other matters beyond Urotronic's control directly affect the device and the results obtained from its use. Urotronic's obligation under this warranty is limited to the repair or replacement of this device and Urotronic shall not be liable for any incidental or consequential loss, damage or expense directly or indirectly arising from the use of this device. Urotronic assumes no liability with respect to devices reused, reprocessed or resterilized and makes no warranties, express or implied, including but not limited for a particular purpose, with respect to such devices. Urotronic, Inc. 2495 Xenium Lane North Minneapolis, MN 55441 USA www.urotronic.com Page 29 of 30 1124-004 rA Draft 14 SYMBOLS USED IN THE DEVICE LABELS Quantity of 1 per box Caution: Federal law restricts this device to sale by or on the order of a physician Catalogue number Lot number Date of manufacture Do not resterilize Do not re-use Do not use if package is damaged Fragile Use-by date Keep away from sunlight Keep dry Manufacturer Does not contain latex Temperature limit 15°C - 30°C (59°F - 86°F) Caution: Consult instructions for use Sterilized using ethylene oxide Single sterile barrier system Single sterile barrier system with protective packaging outside Medical device Unique device identifier Contains a medicinal substance Page 30 of 30 1124-004 rA Draft