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S-1/A
PROTEON THERAPEUTICS INC filed this Form S-1/A on 10/07/2014
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        The primary outcome measure was safety. Adverse events were consistent with the medical conditions experienced by patients with CKD undergoing AVG surgery and showed no significant differences between groups. Some of the data showed indications of efficacy, especially in secondary patency, which is an approvable endpoint for hemodialysis access, for the groups treated with PRT-201 at doses of 10 micrograms and 30 micrograms.

        After reviewing the results from our first Phase 3 clinical trial and if sufficient funds become available, we may commence a clinical trial of PRT-201 in patients undergoing placement of an AVG.

    Peripheral Artery Disease

        In addition to vascular access indications, we are investigating PRT-201 as a treatment for patients with symptomatic peripheral artery disease, or PAD. Patients with lower extremity PAD suffer from stenosis formation in the arteries providing blood to the legs. These patients typically present with exercise-induced leg pain, a condition known as intermittent claudication. Patients with claudication are unable to adequately maintain their activities of daily living because they quickly experience pain that can be resolved only through rest. Severe cases result in critical limb ischemia, or lack of oxygen, and the possibility of amputation. PAD is a global problem affecting a large number of people throughout the industrialized world. Approximately 8 million Americans suffer from PAD.

        Patients with early stage PAD typically undergo lifestyle management such as smoking cessation, weight reduction and/or diabetes management, and treatment with oral medications. Approximately 350,000 patients in the United States do not respond to lifestyle management and have worsening symptoms, resulting in the need for endovascular procedures, typically balloon angioplasty with or without stenting. While these procedures work acutely to restore blood flow, they suffer from poor long-term durability, resulting in the need for repeat procedures.

        We believe that PRT-201 may improve the outcomes associated with angioplasty procedures, resulting in prolonged intervention-free patency while eliminating the need for permanent implant of a stent. We submitted an IND for PRT-201 as a treatment for PAD patients on April 9, 2012. Our initial PAD clinical trial is an ongoing Phase 1, open-label, dose-escalation safety/technical feasibility trial in 16 patients undergoing balloon angioplasty of an occluded or partially occluded superficial femoral or popliteal artery in the leg. Following successful angioplasty, patients are treated with PRT-201 via an FDA-cleared drug delivery catheter that allows PRT-201 to be administered locally in the outer layer of the artery, which is called the adventitia. Patients are being followed for up to 12 months. We expect data from this trial to be available in the second half of 2015.

Manufacturing and Supply

        We depend on third-party contract manufacturers for the production of PRT-201. Our active pharmaceutical ingredient, or API, is produced at our contract manufacturer, Lonza AG, which is required to comply with the FDA's Current Good Manufacturing Practice (cGMP) regulations. PRT-201 finished product is produced at our contract fill/finisher provider, Jubilant HollisterStier, which is required to comply with cGMP regulations. We used API manufactured at Lonza to create finished product that was used in our Phase 2 AVF clinical trial and will be used for our Phase 3 clinical trials. We also plan to manufacture API at Lonza for our commercial launch and future trials. Release and stability testing for API and finished product are performed at PPD, Inc. The tests indicate stability of at least four years for our API and at least six months for our finished product.

        In preparation for commercial launch, we modified our finished product for our Phase 3 trials in order to facilitate ease of administration and fill and finish at 30 microgram doses. The modified finished product is reconstituted with sterile water to create a dosing solution containing 30 micrograms of PRT-201. We demonstrated that the modified finished product had the same elastase activity as the previous finished product using synthetic and natural elastin substrates and documented the same elastin removal from blood vessels following ex vivo treatments. The modified finished product formulation was similar to the

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